108.1 for deferasirox and m/z 430.1 -> 372.2 for the IS.
The method exhibited good linearity over the concentration range of 0.04-40
MUg/mL for deferasirox. The method was successfully applied to a pharmacokinetic
study in 10 Chinese healthy volunteers after oral administration of deferasirox.
PMID- 29328982
TI - Systematic identification of suspected anthelmintic benzimidazole metabolites
using LC-MS/MS.
AB - Metabolite reference standards are often not available, which results in a lack
of MS/MS spectra for library matching. Consequently, the identification of
suspected metabolites proves to be challenging. The present study aims at
structurally elucidating the MS/MS fragmentation behavior of selected
benzimidazole anthelmintics to theoretically predict characteristic product ions
for rapid and systematic tentative metabolite identification. A set of common
characteristic product ions was identified from accurate mass MS/MS experiments
for five parent compounds. It was hypothesized that the mass shift of any
metabolic transformation at the parent molecule also is observable in the mass
spectrum of the corresponding metabolite. This was tested and verified with six
metabolite reference standards and subsequently, formulated as a general
prediction scheme. The approach was integrated into a rapid MSe QTOF workflow and
tested in mouse plasma for mebendazole and its metabolites. The presented scheme
allows the prediction of characteristic product ions for suspected unknown
metabolites. These can be matched with measured product ions of suspected
metabolites for tentative identification. The theoretically predicted spectra can
contribute to the tentative identification of unknown compounds in non-target and
suspect screening approaches.
PMID- 29328983
TI - Social and cognitive control skills in long-life occupation activities modulate
the brain reserve in the behavioural variant of frontotemporal dementia.
AB - BACKGROUND: Cognitive reserve may delay disease onset and mitigate symptoms
presentation in neurodegenerative dementias. Although high occupation levels can
be associated with higher cognitive reserve in the behavioural variant of
frontotemporal dementia (bvFTD), it was never addressed how specific occupation
profiles involving social interaction, executive and attention abilities can
modulate neural reserve in bvFTD. MATERIALS AND METHODS: We retrospectively
included thirty-seven bvFTD patients with clinical-neuropsychological and FDG-PET
brain metabolic data. We considered occupation levels according to 1) a 5-point
scale and 2) the specific cognitive dimensions from the O*Net network database.
We used the Principal Component Analysis (PCA) with the O*Net variables most
representative of "worker" and "occupation" socio-cognitive skills to merge the
best components describing such occupation profiles. We then performed regression
analyses with brain metabolism using either 5-level occupation scale or the PCA
specific profiles as independent variables, controlling for education and disease
severity. RESULTS: According to the brain reserve hypothesis, higher occupation
levels were associated with a more severe hypometabolism in the dorsolateral
prefrontal cortex. In addition, among the identified PCA profiles, social skills
were associated with severe hypometabolism in medial and dorsolateral prefrontal
regions, and cognitive control in the left fronto-insular cortex. DISCUSSION:
This study contributes to define the role of specific occupation profiles as
proxy of cognitive reserve in bvFTD, providing the first evidence for social
interaction and cognitive control skills in life-occupation activities as
influencing factors of neural reserve against neurodegeneration in bvFTD. Jobs
placing high demand on such abilities seem to act as protective factors in bvFTD.
PMID- 29328984
TI - Does college major matter for women's and men's health in midlife? Examining the
horizontal dimensions of educational attainment.
AB - Studies on how education shapes adult health have largely conceptualized
education as the quantity of schooling attained, coined the "vertical dimension"
of education. While this dimension is important, heterogeneity within levels of
education (the "horizontal dimension") may also shape health. Using data from the
2010-2014 American Community Survey on adults aged 45-64 with a Bachelor's degree
(N = 667,362), we investigate the association between a key indicator of adult
health (physical functioning) and an understudied horizontal dimension of
education (college major). We find that physical functioning in midlife varies
significantly by college major. For instance, the odds of poor functioning for
men who majored in Psychology/Social Work were 1.9 (95% CI: 1.7, 2.1) times
greater than for men who majored in Business. However, all college graduates,
regardless of major, report better functioning than non-graduates. We also find
that inequalities in midlife functioning across majors largely reflect
differences in human capital skills and financial returns in the labor market.
Taken together our findings suggest that college major is an important component
of health stratification and should be integrated into the literature on health
inequalities.
PMID- 29328986
TI - Post-anaerobic digestion thermal hydrolysis of sewage sludge and food waste:
Effect on methane yields, dewaterability and solids reduction.
AB - Post-anaerobic digestion (PAD) treatment technologies have been suggested for
anaerobic digestion (AD) to improve process efficiency and assure hygenization of
organic waste. Because AD reduces the amount of organic waste, PAD can be applied
to a much smaller volume of waste compared to pre-digestion treatment, thereby
improving efficiency. In this study, dewatered digestate cakes from two different
AD plants were thermally hydrolyzed and dewatered, and the liquid fraction was
recirculated to a semi-continuous AD reactor. The thermal hydrolysis was more
efficient in relation to methane yields and extent of dewaterability for the cake
from a plant treating waste activated sludge, than the cake from a plant treating
source separated food waste (SSFW). Temperatures above 165 degrees C yielded the
best results. Post-treatment improved volumetric methane yields by 7% and the COD
reduction increased from 68% to 74% in a mesophilic (37 degrees C) semi
continuous system despite lowering the solid retention time (from 17 to 14 days)
compared to a conventional system with pre-treatment of feed substrates at 70
degrees C. Results from thermogravimetric analysis showed an expected increase in
maximum TS content of dewatered digestate cake from 34% up to 46% for the SSFW
digestate cake, and from 17% up to 43% in the sludge digestate cake, after the
PAD thermal hydrolysis process (PAD-THP). The increased dewatering alone accounts
for a reduction in wet mass of cake leaving the plant of 60% in the case of
sludge digestate cake. Additionaly, the increased VS-reduction will contribute to
further reduce the mass of wet cake.
PMID- 29328985
TI - Standing on a sliding board affects generation of anticipatory and compensatory
postural adjustments.
AB - Postural control is compromised in the presence of body instability. We studied
anticipatory and compensatory postural adjustments people use to maintain balance
while standing on an unstable surface and performing voluntary arm movements.
Nine healthy participants stood on a sliding board (that was either locked and as
such motionless or unlocked and as such free to move in the anterior-posterior
direction) and performed fast bilateral arms flexion. Arm acceleration, bilateral
electromyographic activity (EMG) of the trunk and lower extremity muscles and
center of pressure (COP) displacements were recorded and analyzed within the
intervals typical for the anticipatory (APAs) and compensatory (CPAs) postural
adjustments. Peaks of acceleration of the arm movements were not different
between the locked and unlocked conditions. Larger EMG integrals were seen in the
muscles of the lower extremity in both APAs and CPAs when standing on the
unlocked sliding board. No significant difference was observed in the trunk
muscles. Larger maximum COP displacement was seen when participants stood on the
locked board. The results demonstrated that when standing on a free to move
sliding board and performing bilateral arm flexion, the central nervous system
(CNS) does not slow down the arm movements; instead it modifies activation of the
lower extremity muscles. The observed differences in APAs and CPAs between the
locked and unlocked conditions suggest that the CNS employs similar strategy
while controlling the focal part of the task and adjusts the activity of muscles
that are close to the source of instability to control postural task.
PMID- 29328987
TI - Total mercury content in commercial swordfish (Xiphias gladius) from different
FAO fishing areas.
AB - Mercury (Hg) is a global pollutant that affect human and ecosystem health. It is
transferred through trophic level and bio magnification in the food chain. In
this study, total Hg was measured in the muscular tissue of samples of swordfish
(Xiphias gladius) from different FAO fishing areas and imported in Italy between
2014 and 2017. Total mercury concentrations of muscular tissues were determined
using cold vapour atomic absorption spectrometry. In order to assess the health
risk associated with human consumption of this fish, the Hg intake values were
calculated and compared with those of provisional tolerable daily intake (PTDI)
(0.57 MUg/kg b.w.) as fixed by the Food and Agriculture Organization/World Health
Organization (FAO/WHO). The estimated PTDI (provisional tolerable daily intake)
were lower for adults (0.40 MUg/kg b.w./day) but not for children (0.97 MUg/kg
b.w./day), and therefore is considered to pose an alert for children with the
present fish consumption volume.
PMID- 29328988
TI - Carboxymethyl cellulose stabilized ZnO/biochar nanocomposites: Enhanced
adsorption and inhibited photocatalytic degradation of methylene blue.
AB - Biochar(BC)-supported nanoscaled zinc oxide (nZO) was encapsulated either with
(nZORc/BC) or with no (nZOR/BC) sodium carboxymethyl cellulose (CMC). The X-ray
diffraction and ultraviolet (UV)-visible-near infrared spectrophotometry revealed
that nZO of 16, 10, and 20 nm with energy band gaps of 2.79, 3.68 and 2.62 eV
were synthesized for nZOR/BC, nZORc/BC and nZO/BC, respectively. The Langmuir
isotherm predicted saturated sorption of methylene blue (MB) was 17.01 g kg-1 for
nZORc/BC, over 19 times greater than nZOR/BC and nZO/BC. Under UV irradiation,
10.9, 61.6, 83.1, and 41.6% of MB were degraded for nZORc/BC, nZO/BC, nZOR/BC and
BC. The scavenging experiment revealed hydroxyl radical dominated CMC
degradation. Exogenous CMC (2 g L-1) increased MB sorption from 10.6% to 73.1%,
but decreased MB degradation from 80.7% to 41.1%, relative to nZOR/BC. Thus, CMC
could increase MB sorption by electrostatic attraction and other possible
mechanisms. The compromised MB degradation may be ascribed to reduced
availability of hydroxyl and superoxide radicals to degrade MB, and increased
band gap energy of ZnO.
PMID- 29328989
TI - Inhibition of UDP-glucuronosyltransferases (UGTs) by phthalate monoesters.
AB - Phthalate monoesters are important metabolites of phthalate esters (PAEs) which
have been extensively utilized in industry. This study aims to investigate the
inhibition of phthalate monoesters on the activity of various isoforms of UDP
glucuronosyltransferases (UGTs), trying to elucidate the toxicity mechanism of
environmental endocrine disruptors from the new perspectives. In vitro
recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was
employed to evaluate 8 kinds of phthalate monoesters on 11 sorts of main human
UGT isoforms. 100 MUM phthalate monoesters exhibited negligible inhibition
towards the activity of UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A10, UGT2B4, UGT2B7,
UGT2B15 and UGT2B17. The activity of UGT1A7 was strongly inhibited by
monoethylhexyl phthalate (MEHP), but slightly inhibited by all the other
phthalate monoesters. UGT1A9 was broadly inhibited by monobenzyl phthalate
(MBZP), monocyclohexyl phthalate (MCHP), MEHP, monohexyl phthalate (MHP) and
monooctyl phthalate (MOP), respectively. MEHP exhibited competitive inhibition
towards UGT1A7, and MBZP, MCHP, MEHP, MHP and MOP showed competitive inhibition
towards UGT1A9. The inhibition kinetic parameters (Ki) were calculated to be
11.25 MUM for MEHP-UGT1A7, and 2.13, 0.09, 1.17, 7.47, 0.16 MUM for MBZP-UGT1A9,
MCHP-UGT1A9, MEHP-UGT1A9, MHP-UGT1A9, MOP-UGT1A9, respectively. Molecular docking
indicated that both hydrogen bonds formation and hydrophobic interactions
significantly contributed to the interaction between phthalate monoesters and UGT
isoforms. All these information will be beneficial for understanding the adverse
effects of PAEs.
PMID- 29328991
TI - Comparison of effects of charge delocalization and pi-electron delocalization on
the stability of monocyclic compounds.
AB - Aromaticities and stabilities of ortho, meta, and para isomers of some
derivatives of benzene, C5H5- and C7H7+ were studied and compared basis on the
NICS index and their relative energies. For the benzene and C7H7+ derivatives,
the ortho isomers with less stability were more aromatic. This discrepancy was
also observed for the molecules with conjugated and non-conjugated pi-electrons.
However, for the charged conjugated systems, the structures with delocalized
charge were more stable. Effect of electron withdrawing (EWGs) and electron
donating groups (EDGs) on the electron delocalization and stability of the
neutral and charged molecules was investigated. It was observed that the EWDs and
EDGs change the stability trend of the neutral systems, while in the case of
charged molecules, the isomers with delocalized charge were more stable
regardless of the type of substituents. Although both pi-electron delocalization
and charge delocalization stabilize the aromatic and conjugated systems, effect
of charge delocalization on the stability is more than that of pi-electron
delocalization.
PMID- 29328990
TI - The amyloidogenicity of the influenza virus PB1-derived peptide sheds light on
its antiviral activity.
AB - The influenza virus polymerase complex is a promising target for new antiviral
drug development. It is known that, within the influenza virus polymerase
complex, the PB1 subunit region from the 1st to the 25th amino acid residues has
to be is in an alpha-helical conformation for proper interaction with the PA
subunit. We have previously shown that PB1(6-13) peptide at low concentrations is
able to interact with the PB1 subunit N-terminal region in a peptide model which
shows aggregate formation and antiviral activity in cell cultures. In this paper,
it was shown that PB1(6-13) peptide is prone to form the amyloid-like fibrillar
aggregates. The peptide homo-oligomerization kinetics were examined, and the
affinity and characteristic interaction time of PB1(6-13) peptide monomers and
the influenza virus polymerase complex PB1 subunit N-terminal region were
evaluated by the SPR and TR-SAXS methods. Based on the data obtained, a
hypothesis about the PB1(6-13) peptide mechanism of action was proposed: the
peptide in its monomeric form is capable of altering the conformation of the PB1
subunit N-terminal region, causing a change from an alpha helix to a beta
structure. This conformational change disrupts PB1 and PA subunit interaction
and, by that mechanism, the peptide displays antiviral activity.
PMID- 29328992
TI - Transcriptome-wide identification and competitive disruption of sacum-binding
partners in human colorectal cancer.
AB - Human sacum is regulatory adaptor protein involved in cellular signaling network
of colorectal cancer. Molecular evidences suggest that the protein is integrated
into oncogenic signaling network by binding to SH3-containing proteins through
its proline-rich motifs. In this study, we have performed a transcriptome-wide
analysis and identification of sacum-binding partners in the genome profile of
human colorectal cancer. The sacum-binding potency of SH3-containing proteins
found in colorectal cancer was investigated by using bioinformatics modeling and
intermolecular binding analysis. With the protocol we were able to predict those
high-affinity domain binders of the proline-rich peptides of human sacum in a
high-throughput manner, and to analyze sequence-specific interaction in the
domain-peptide recognition at molecular level. Consequently, a number of putative
domain binders with both high affinity and specificity were identified, from
which the Src SH3 domain was selected as a case study and tested for its binding
activity towards the sacum peptides. We also designed two peptide variants that
may have potent capability to competitively disrupt sacum interaction with its
partners.
PMID- 29328993
TI - Activity-based classification circumvents affinity prediction problems for
pyrrolidine carboxamide inhibitors of InhA.
AB - Developing reliable structure-based activity prediction models for a particular
ligand series can be challenging if the target is flexible and the affinity range
of the training compounds is narrow. For a data set of 44 pyrrolidine carboxamide
inhibitors of the mycobacterial enoyl-ACP-reductase InhA this proved to be case,
as scoring methods of various origin and complexity did not succeed in providing
practically useful correlations with experimental inhibition data. In contrast,
logistic regression models for activity-based classification trained with
combinations of scoring functions led to good separation of the more active
inhibitors from the weakest compounds. The approach is suggested as an
alternative in cases where classical scoring and ranking procedures fail.
PMID- 29328994
TI - Does high pressure have any effect on the structure of alpha amylase and its
ability to binding to the oligosaccharides having 3-7 residues? Molecular
dynamics study.
AB - Studies have shown that deletion of amino acids from the C-terminus of amylase do
not alter its amylolytic activity. Although high pressure is used to modify the
structure and function of this enzyme, the effects of high pressures on the
structures of the wild-type and truncated amylases have not yet been understood
at the molecular level. Using molecular dynamic simulations and docking, we
studied the structures of wild-type and truncated Taka-amylases at high pressures
(1000-4000 bar). To construct the truncated Taka-amylase, 50 and 100 C-terminal
residues were removed in two separate steps. Results of simulation showed that,
although the overall shape partly agglomerates with rise in pressure, high
pressure fails to modify the structure of the barrel-like region of the beta
sheet in the wild-type and truncated enzymes. A comparison of contact graphs
revealed that the changes at the N-terminus were less extensive than those at the
C-terminus. Further analysis showed that 10 regions of the secondary structures
changed due to pressure change in wild-type amylase, of which 6 regions were
associated with the loops and 4 with helix, while the structure of beta-sheets
remained unchanged. The docking of maltotriose, maltotetraose, maltopentaose,
maltohexaose, and maltoheptaose with the averaged structures obtained from
different simulations was conducted to characterize the influence of pressure on
the activities of the wild-type and truncated enzymes. The results showed that
maltoheptaose made hydrophobic contacts with residues Tyr238-Asp117-Tyr82-Leu166
Leu232-Tyr155 and hydrogen contacts with residues Asp233-Gly234-Asp206-Arg204
His296-Glu230. Similar results were obtained for other malto-oligosaccharides.
PMID- 29328995
TI - FilTer BaSe: A web accessible chemical database for small compound libraries.
AB - Finding novel chemical agents for targeting disease associated drug targets often
requires screening of large number of new chemical libraries. In silico methods
are generally implemented at initial stages for virtual screening. Filtering of
such compound libraries on physicochemical and substructure ground is done to
ensure elimination of compounds with undesired chemical properties. Filtering
procedure, is redundant, time consuming and requires efficient
bioinformatics/computer manpower along with high end software involving huge
capital investment that forms a major obstacle in drug discovery projects in
academic setup. We present an open source resource, FilTer BaSe- a
chemoinformatics platform (http://bioinfo.net.in/filterbase/) that host fully
filtered, ready to use compound libraries with workable size. The resource also
hosts a database that enables efficient searching the chemical space of around
348,000 compounds on the basis of physicochemical and substructure properties.
Ready to use compound libraries and database presented here is expected to aid a
helping hand for new drug developers and medicinal chemists.
PMID- 29328996
TI - Acute and sub-acute neurological toxicity in children treated for acute
lymphoblastic leukemia.
AB - Eighty percent of children with acute lymphoblastic leukemia (ALL) survive with
current treatments. Neurotoxicity is an infrequent adverse event. We describe
clinical presentations of neurological toxicity, phases of treatment when these
adverse events were more frequent and patients outcome. From January-1995 to
December-2015, 1379 ALL cases were admitted. Neurotoxicity was diagnosed in 49
patients (3.6%) and classified according to neurological syndromes. Medical
records, laboratory-tests and images were reviewed. The diagnosed syndromes were:
a) Methotrexate-leukoencephalopathy (MLE) (35.4%); b) Cerebral-venous-sinus
thrombosis following L-Asparaginase administration (26.5%); c) Vincristine
induced-vocal-cord paralysis (VVCP) (14.2%); d) Stroke-associated vasospasm
(14%), after high-dose methotrexate e) Severe polyneuropathy (6.1%); f)
Methotrexate myelopathy (2%); and g) Pseudotumor-cerebri (2%) associated with
corticosteroid therapy. Neurotoxicity was diagnosed during induction in 55% of
cases. We conclude that MLE was the most frequent syndrome. VVCP was observed in
infants and Down patients. Seizure was the most common symptom and toxicity
occurred mainly during induction phase.
PMID- 29328997
TI - Synthesis, biological evaluation and molecular modeling of novel
thienopyrimidinone and triazolothienopyrimidinone derivatives as dual anti
inflammatory antimicrobial agents.
AB - New thienopyrimidinone and triazolothienopyrimidinone derivatives have been
synthesized. These compounds were subjected to anti-inflammatory and
antimicrobial activity screening aiming to identify new candidates that have dual
anti-inflammatory and antimicrobial activities. Compounds 5, 7 and 10a showed
minimal ulcerogenic effect and high selectivity towards human recombinant COX-2
over COX-1 enzyme. Their docking outcome correlated with their biological
activity and assured the high selectivity binding towards COX-2. In addition,
they could act safely up to 80 mg/kg orally or 40 mg/kg parentrally. The
antimicrobial screening showed that compound 10a displayed distinctive inhibitory
effect on the growth of Escherichia coli comparable to that of ampicillin.
Moreover, compounds 5, 7, 9 and 12a possessed 50% of the inhibitory activity of
ampicillin against E. coli. Thus, compounds 5, 7 and 10a represent promising dual
acting anti-inflammatory and antimicrobial agents. This work provides rewarding
template enriching the chemical space for dual anti-inflammatory anti-microbial
activities.
PMID- 29328998
TI - Immunization of mice with egG1Y162-1/2 provides protection against Echinococcus
granulosus infection in BALB/c mice.
AB - AIMS: This study is to predict and purify the T-B combined epitopes of egG1Y162
antigen in Echinococcus granulosus, and to evaluate their immunogenicity in mice.
METHODS: The bioinformatics software was used to predict the T-B combined
epitopes of egG1Y162 antigen. Recombinant egG1Y161/2 peptides were constructed,
expressed and purified. Mice were immunized with egG1Y161/2 peptides. The serum
and spleen cells were isolated. The isolated spleen cells were stimulated with
egG1Y161/2 peptides in vitro and the culture supernatant was collected. The
levels of IgG in serum and levels of IL-4 and IFN-gamma in the culture
supernatant were measured by ELISA. The weight and number of the fresh hydatid
cysts were evaluated. The serum ptotoscolicidal activity was measured by the
complement dependent cytotoxicity assay. RESULTS: Peptides of 6-19aa, 64-82aa,
106-119aa were predicted as T-B combined epitopes of egG1Y162 antigen. And,
recombinant protein egG1Y162-1 or egG1Y162-2, which contained T-B combined
epitope(s) of the 6-19aa, or the 64-82aa and the 106-119aa in egG1Y162 antigen,
respectively, was successfully expressed and purified. Serum IgG levels of mice
immunized with egG1Y162-1/2 were significantly increased during the immune
response to Echinococcus granulosus. The levels of IFN-gamma, IL-4 and the ratio
of IFN-gamma/IL-4 after egG1Y162-1/2 immunization were significantly higher.
Weight and number of the fresh hydatid cysts in egG1Y162-1/2 immunized mice was
significantly decreased. And, the serum protoscolicidal activity after egG1Y162
1/2 immunization was enhanced. CONCLUSIONS: The egG1Y162-1/2 induces production
of serum IgG levels and Th1 cell immune response, which enhances the protective
immunity in Echinococcus granulosus challenged mice and thus may be used as a
potential vaccine candidate.
PMID- 29328999
TI - Discovery of novel piperonyl derivatives as diapophytoene desaturase inhibitors
for the treatment of methicillin-, vancomycin- and linezolid-resistant
Staphylococcus aureus infections.
AB - Inhibition of S. aureus diapophytoene desaturase (CrtN) could serve as an
alternative approach for addressing the tricky antibiotic resistance by blocking
the biosynthesis of carotenoid pigment which shields the bacterium from host
oxidant killing. In this study, we designed and synthesized 44 derivatives with
piperonyl scaffold targeting CrtN and the structure-activity relationships (SARs)
were examined extensively to bring out the discovery of 21b with potent efficacy
and better hERG safety profile compared to the first class CrtN inhibitor
benzocycloalkane derivative 2. Except the excellent pigment inhibitory activity
against wild-type S. aureus, 21b also showed excellent pigment inhibition against
four pigmented MRSA strains. In addition, H2O2 killing and human whole blood
killing assays proved 21b could sensitize S. aureus to be killed under oxidative
stress conditions. Notably, the murine study in vivo validated the efficacy of
21b against pigmented S. aureus Newman, vancomycin-intermediate S. aureus Mu50
and linezolid-resistant S. aureus NRS271.
PMID- 29329000
TI - Synthesis of C3-Neoglycosides of digoxigenin and their anticancer activities.
AB - Cardiac glycosides exhibit significant anticancer effects and the glycosyl
substitution at C3 position of digoxigenin is pivotal for their biological
activity. In order to study the structure-activity relationship (SAR) of cardiac
glycosides toward cancers and explore more potent anticancer agents, a series of
C3-O-neoglycosides and C3-MeON-neoglycosides of digoxigenin were synthesized by
the Koenigs-Knorr and neoglycosylation method, respectively. In addition,
digoxigenin bisdigitoxoside and monodigitoxoside were prepared from digoxin by
sodium periodate (NaIO4) oxidation and 6-aminocaproic acid hydrolysis. The SAR
analysis revealed that C3-O-neoglycosides of digoxigenin exhibited stronger
cytotoxicity and induction of Nur77 expression of tumor cells than C3-MeON
neoglycosides. Also, 3beta-O-glycosides exhibited stronger anticancer effects
than 3alpha-O-glycosides. Among them, 3beta-O-(beta-l-fucopyranosyl)-digoxigenin
(3i) showed the highest activity on induction of Nur77 expression and
translocation from the nucleus to cytoplasm, leading to cancer cell apoptosis.
PMID- 29329001
TI - Improved antibacterial activity of a marine peptide-N2 against intracellular
Salmonella typhimurium by conjugating with cell-penetrating peptides
bLFcin6/Tat11.
AB - Salmonellae, gram-negative bacteria, are facultative intracellular pathogens that
cause a number of diseases in animals and humans. The poor penetration ability of
antimicrobial agents limits their use in the treatment of intracellular bacterial
infections. In this study, the cell-penetrating peptides (CPPs) bLFcin6 and Tat11
were separately conjugated to the antimicrobial peptide N2, and the antibacterial
activity and pharmacodynamics of the CPPs-N2 conjugates were first evaluated
against Salmonellae typhimurium in vitro and in macrophage cells. The
cytotoxicity, cellular uptake and mechanism of cellular internalization of the
CPPs-N2 conjugates were also examined in RAW264.7 cells. Similar to N2, CPPs-N2
have two reverse beta-sheets and three loops. The minimal inhibitory
concentration (MIC) of CPPs-N2 was approximately 2 MUM, which was higher than
that of N2 (0.8 MUM). The dose-time curves and cytotoxicity assay showed that
both peptide conjugates were more effective than N2 alone at concentrations
ranging from 0.25 to 1 * MIC, and they exhibited low cytotoxicity (9.78%-13.54%)
at 100 MUM. After 0.5 h incubation, the cell internalization ratio of B6N2 and
T11N2 exceeded 28.3% and 93.5%, respectively, which was higher than that of N2.
The uptake of B6N2 and T11N2 was reduced by low temperature (82.1%-91.7%),
chlorpromazine (35.7%-75.1%), and amiloride (26.0%-52.1%), indicating that
macropinocytosis and clathrin-mediated endocytosis may be involved. Approximately
98.85% and 91.35% of bacteria were killed within 3 h by T11N2 and B6N2,
respectively, which was higher than the percentage killed by N2 (69.74%).
Compared with the bactericidal activity of N2 alone, the bactericidal activity of
T11N2 and B6N2 was increased by 53.7%-99.6% and 85.3-85.8%, respectively. Both
CPPs-N2 conjugates may be excellent candidates for novel antimicrobial agents to
treat infectious diseases caused by intracellular pathogens.
PMID- 29329002
TI - Integration of multi-scale molecular modeling approaches with experiments for the
in silico guided design and discovery of novel hERG-Neutral antihypertensive
oxazalone and imidazolone derivatives and analysis of their potential restrictive
effects on cell proliferation.
AB - AT1 antagonists is the most recent drug class of molecules against hypertension
and they mediate their actions through blocking detrimental effects of
angiotensin II (A-II) when acts on type I (AT1) A-II receptor. The effects of AT1
antagonists are not limited to cardiovascular diseases. AT1 receptor blockers may
be used as potential anti-cancer agents - due to the inhibition of cell
proliferation stimulated by A-II. Therefore, AT1 receptors and the A-II
biosynthesis mechanisms are targets for the development of new synthetic drugs
and therapeutic treatment of various cardiovascular and other diseases. In this
work, multi-scale molecular modeling approaches were performed and it is found
that oxazolone and imidazolone derivatives reveal similar/better interaction
energy profiles compared to the FDA approved sartan molecules at the binding site
of the AT1 receptor. In silico-guided designed hit molecules were then
synthesized and tested for their binding affinities to human AT1 receptor in
radioligand binding studies, using [125I-Sar1-Ile8] AngII. Among the compounds
tested, 19d and 9j molecules bound to receptor in a dose response manner and with
relatively high affinities. Next, cytotoxicity and wound healing assays were
performed for these hit molecules. Since hit molecule 19d led to deceleration of
cell motility in all three cell lines (NIH3T3, A549, and H358) tested in this
study, this molecule is investigated in further tests. In two cell lines (HUVEC
and MCF-7) tested, 19d induced G2/M cell cycle arrest in a concentration
dependent manner. Adherent cells detached from the plates and underwent cell
death possibly due to apoptosis at 19d concentrations that induced cell cycle
arrest.
PMID- 29329003
TI - Modified forest rotation lengths: Long-term effects on landscape-scale habitat
availability for specialized species.
AB - We evaluated the long-term implications from modifying rotation lengths in
production forests for four forest-reliant species with different habitat
requirements. By combining simulations of forest development with habitat models,
and accounting both for stand and landscape scale influences, we projected
habitat availability over 150 years in a large Swedish landscape, using rotation
lengths which are longer (+22% and +50%) and shorter (-22%) compared to current
practices. In terms of mean habitat availability through time, species requiring
older forest were affected positively by extended rotations, and negatively by
shortened rotations. For example, the mean habitat area for the treecreeper
Certhia familiaris (a bird preferring forest with larger trees) increased by 31%
when rotations were increased by 22%, at a 5% cost to net present value (NPV) and
a 7% decrease in harvested volume. Extending rotation lengths by 50% provided
more habitat for this species compared to a 22% extension, but at a much higher
marginal cost. In contrast, the beetle Hadreule elongatula, which is dependent on
sun-exposed dead wood, benefited from shortened rather than prolonged rotations.
Due to an uneven distribution of stand-ages within the landscape, the relative
amounts of habitat provided by different rotation length scenarios for a given
species were not always consistent through time during the simulation period. If
implemented as a conservation measure, prolonging rotations will require long
term strategic planning to avoid future bottlenecks in habitat availability, and
will need to be accompanied by complementary measures accounting for the
diversity of habitats necessary for the conservation of forest biodiversity.
PMID- 29329004
TI - Contemporary enzyme based technologies for bioremediation: A review.
AB - The persistent disposal of xenobiotic compounds like insecticides, pesticides,
fertilizers, plastics and other hydrocarbon containing substances is the major
source of environmental pollution which needs to be eliminated. Many contemporary
remediation methods such as physical, chemical and biological are currently being
used, but they are not sufficient to clean the environment. The enzyme based
bioremediation is an easy, quick, eco-friendly and socially acceptable approach
used for the bioremediation of these recalcitrant xenobiotic compounds from the
natural environment. Several microbial enzymes with bioremediation capability
have been isolated and characterized from different natural sources, but less
production of such enzymes is a limiting their further exploitation. The genetic
engineering approach has the potential to get large amount of recombinant
enzymes. Along with this, enzyme immobilization techniques can boost the half
life, stability and activity of enzymes at a significant level. Recently,
nanozymes may offer the potential bioremediation ability towards a broad range of
pollutants. In the present review, we have described a brief overview of the
microbial enzymes, different enzymes techniques (genetic engineering and
immobilization of enzymes) and nanozymes involved in bioremediation of toxic,
carcinogenic and hazardous environmental pollutants.
PMID- 29329005
TI - Costs and benefits of biogas recovery from communal anaerobic digesters treating
domestic wastewater: Evidence from peri-urban Zambia.
AB - Communal anaerobic digesters (ADs) have been promoted as a waste-to-energy
strategy that can provide sanitation and clean energy co-benefits. However,
little empirical evidence is available regarding the performance of such systems
in field conditions. This study assesses the wastewater treatment efficiency,
energy production, greenhouse gas (GHG) emissions, and financial costs and
benefits of communal ADs used for domestic wastewater treatment in Zambia.
Primary data on the technical performance of 15 ADs were collected over a 6-month
period and in-person interviews were conducted with heads of 120 households.
Findings from this study suggest that ADs offer comparable wastewater treatment
efficiencies and greater GHG emission reduction benefits relative to conventional
septic tanks (STs), with the greatest benefits in settings with reliable access
to water, use of low efficiency solid fuels and with sufficient demand for biogas
in proximity to supply. However, absent a mechanism to monetize additional
benefits from biogas recovery, ADs in this context will not be a financially
attractive investment relative to STs. Our financial analysis suggests that,
under the conditions in this study, a carbon price of US$9 to $28 per tCO2e is
necessary for positive investment in ADs relative to STs. Findings from this
study contribute empirical evidence on ADs as a sanitation and clean energy
strategy, identify conditions under which the greatest benefits are likely to
accrue and inform international climate efforts on the carbon price required to
attract investment in emissions reduction projects such as ADs.
PMID- 29329006
TI - Ongoing unmet needs in treating estrogen receptor-positive/HER2-negative
metastatic breast cancer.
AB - Estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2
negative (HER2-) advanced or metastatic breast cancer (MBC) is the most common
MBC subtype and currently remains incurable, with a median overall survival of
24.8 months (95% confidence interval, 21.3-30.3). Common sites of metastases are
bone, viscera, and brain, causing significant symptoms that negatively affect
patient functioning, quality of life (QoL), and work productivity. Guidelines
state that endocrine therapy (ET) is preferable to chemotherapy as first-line
treatment for patients with ER+ MBC, regardless of limited visceral metastases,
unless rapid tumor response is required or ET resistance is suspected. Although
response rates up to 40% have been reported for first-line MBC treatment, the
majority of initial responders eventually develop ET resistance. Notwithstanding
the steep decline in efficacy between first and later lines of ET, some patients
may receive chemotherapy earlier than necessary. Although new treatments have
been approved for patients with ER+/HER2- advanced or MBC in the past decade,
neither survival nor QoL appear to have improved significantly. Thus, there
remain significant unmet needs for this patient population, including improved
survival, maintaining or improving patient QoL, and emphasizing the importance of
treatment selection to assist healthcare practitioners managing patient care. In
this review, we identify current challenges and unmet needs in this patient
population, review cutting-edge treatments, and provide clinically relevant
suggestions for treatment selection that can optimize outcomes and patients'
health-related QoL.
PMID- 29329008
TI - Selective formation of copper nanoparticles from acid mine drainage using
nanoscale zerovalent iron particles.
AB - Nanoscale zerovalent iron (nZVI) has been investigated for the selective
formation of Cu nanoparticles from acid mine drainage (AMD) taken from a legacy
mine site in the UK. Batch experiments were conducted containing unbuffered (pH
2.67 at t = 0) and pH buffered (pH < 3.1) AMD which were exposed to nZVI at 0.1
2.0 g/L. Results demonstrate that nZVI is selective for Cu, Cd and Al removal
(>99.9% removal of all metals within 1 h when nZVI >= 1.0 g/L) from unbuffered
AMD despite the coexistent of numerous other metals in the AMD, namely: Na, Ca,
Mg, K, Mn and Zn. An acidic pH buffer enabled similarly high Cu removal but
maximum removal of only <1.5% and <0.5% Cd and Al respectively. HRTEM-EDS
confirmed the formation of discrete spherical nanoparticles comprised of up to
68% wt. Cu, with a relatively narrow size distribution (typically 20-100 nm
diameter). XPS confirmed such nanoparticles as containing Cu degrees , with the
Cu removal mechanism therefore likely via cementation with Fe degrees . Overall
the results demonstrate nZVI as effective for the one-pot and selective formation
of Cu degrees -bearing nanoparticles from acidic wastewater, with the technique
therefore potentially highly useful for the selective upcycling of dissolved Cu
in wastewater into high value nanomaterials.
PMID- 29329007
TI - The relative strength of attitudes versus perceived drinking norms as predictors
of alcohol use.
AB - Social cognitive factors such as perceived norms and personal attitudes toward
alcohol consumption are reliable predictors of alcohol use and related problems.
The current study aimed to evaluate the relative importance of one's attitude
toward alcohol use as a unique and important predictor of drinking related
outcomes when directly compared to perceived descriptive and injunctive norms.
Participants were mandated students (n=568; 28% female) who violated a campus
alcohol policy and received a Brief Motivational Intervention. Analyses included
the use of linear regression for prospective predictions to evaluate the relative
importance of predictors which included perceived descriptive norms and
injunctive norms, and attitudes toward moderate and heavy alcohol use. Overall,
the results indicate that one's attitude toward heavy alcohol use is a stronger
predictor of drinks per week, binge frequency, as well as alcohol related
problems when directly compared to norms. Thus, the findings of the current study
provide a compelling rationale for incorporating attitudes in the development and
refinement of intervention strategies.
PMID- 29329009
TI - Well-controlled in-situ growth of 2D WO3 rectangular sheets on reduced graphene
oxide with strong photocatalytic and antibacterial properties.
AB - Finding the materials, which help to control the water pollution caused by
organic and bacterial pollutants is one of the challenging tasks for the
scientific community. 2D sheets of WO3 and composite of WO3 and reduced graphene
oxide (rGO) have been synthesized in a well-controlled way using a hydrothermal
method. The as synthesized 2D sheet of WO3 and rGO-WO3 composite were
characterized by various techniques. The 2D sheets of WO3 and rGO-WO3 composite
are efficiently utilized for the photocatalytic degradation of methylene blue
(MB) and Rhodamine B (RhB) dyes under sunlight. The rGO-WO3 composite reveals
excellent photocatalytic degradation of RhB dye by degrading it upto 85% under
sunlight. However, the MB dye was degraded by 32%. The greater degradation of RhB
dye was explained in terms of the molecular electrostatic potential. We found
that RhB has a more positive potential compared to MB dye where O2- and OH
radicals interact more strongly, resulting in a greater degradation of the RhB
dye. The antibacterial activity of the 2D sheets of WO3 and rGO-WO3composite was
also investigated on gram positive (B. subtilis) and gram negative (P.
aeroginosa) microbes for the first time.
PMID- 29329010
TI - UVA-UVB activation of hydrogen peroxide and persulfate for advanced oxidation
processes: Efficiency, mechanism and effect of various water constituents.
AB - In the present work we investigate the activation efficiency of H2O2 and S2O82-
using UVA and UVB radiation. Bisphenol-A (BPA) is used as model pollutants to
estimate the oxidative process efficiency in simulated and real sewage treatment
plant waters. Particular attention is paid to the BPA removal efficiency and to
the radical mechanism involvement considering the effect of typical inorganic
water constituents (carbonates and chloride ions) and organic matter. Despite a
detrimental effect observed when carbonate ions are in solution using both
hydrogen peroxide and persulafate, the presence of high chloride ions
concentration was found to improve BPA removal using S2O82- as radical precursor.
This enhancement, investigated combining chemical kinetic model approach and
laser flash photolysis experiments, is attributed to the formation of hydroxyl
radical and chlorine radical species from sulfate radical. Different
transformation products are identified by means of GC-MS and HPLC-MS analyses.
Moreover, experiments using sewage treatment plant water (STPW) spiked with BPA
are performed in order to assess the efficiency of oxidative processes in a
simulated treatment systems activated using UVA + UVB radiations.
PMID- 29329011
TI - Removal of ozonation products of pharmaceuticals in laboratory Moving Bed Biofilm
Reactors (MBBRs).
AB - The major pathway of pharmaceuticals from urban applications to urban surface
waters is via wastewater treatment plants. Ozonation is able to remove
pharmaceuticals from wastewater effluents. However, during that reaction,
ozonation products are formed. Some ozonation products were found to be
persistent and have adverse effect on the environment. Moving bed bio reactors
(MBBRs) were tested for the removal of the ozonation products of macrolide
antibiotics and diclofenac at two different concentration levels 1 MUg/L and 10
MUg/L in laboratory reactors. It was found that the MBBRs are capable of
degrading these compounds without back-transformation into the parent compounds.
However, reaction rate constants and the degradation kinetics varied for
different compounds and different concentrations. Depending on compound and
conditions, the degradation reaction kinetics was found to follow either i) zero
order ii) first order or iii) lag phase succeeded by first order. The study has
proven that MBBRs have the potential to be efficient in polishing post ozonation
treatment.
PMID- 29329012
TI - Oxidative transformation kinetics and pathways of albendazole from reactions with
manganese dioxide.
AB - Albendazole (ABZ) is a benzimidazole-based veterinary anthelmintic used
extensively in the treatment of intestinal parasites. Due to its high
hydrophobicity, ABZ tends to accumulate in soils and sediments in the
environment. This study aims to investigate ABZ's possible degradation by
manganese oxides. Minor effects from ionic strength and metal cations on ABZ
degradation were observed. By contrast, decrease of pH greatly enhanced the
reaction rate. Surface complexation between ABZ and MnO2 was indicated to be the
dominant control in the reaction kinetics. Suppression by the presence of co
solvents was negatively proportional to the solvent polarities (suppression from
high to low: diethyl ether ~ n-butanol > ethanol > methanol > acetonitrile).
Humic acid was found to cause significant inhibition due to the reductive
dissolution of MnO2. Four hydrolysis and six oxidative products were identified.
ABZ and its hydrolysis products containing the propylthio side chain underwent
the same oxidative transformation to form their corresponding sulfoxide
compounds. Dehydrogenative coupling reaction between sulfoxide products and
hydrolysis products could occur to generate dimers. All hydrolysis and oxidative
products were eluted faster than ABZ in liquid chromatogram, suggesting that the
spreading out of ABZ will be significantly enhanced if reacting with MnO2.
PMID- 29329013
TI - Antiobesity effect of Lactobacillus reuteri 263 associated with energy metabolism
remodeling of white adipose tissue in high-energy-diet-fed rats.
AB - Obesity is a serious and costly issue to the medical welfare worldwide.
Probiotics have been suggested as one of the candidates to resolve the obesity
associated problems, but how they combat obesity is not fully understood. Herein,
we investigated the effects of Lactobacillus reuteri 263 (L. reuteri 263) on
antiobesity using four groups of Sprague-Dawley rats (n=10/group), namely, C
(normal diet with vehicle treatment), HE [high-energy diet (HED) with vehicle
treatment], 1X (HED with 2.1*109 CFU/kg/day of L. reuteri 263) and 5X (HED with
1.05*1010 CFU/kg/day of L. reuteri 263), for 8 weeks. L. reuteri 263 improved the
phenomenon of obesity, serum levels of proinflammatory factors and antioxidant
enzymes. More importantly, L. reuteri 263 increased oxygen consumption in white
adipose tissue (WAT). The mRNA expressions of thermogenesis genes uncoupling
protein-1, uncoupling protein-3, carnitine palmitoyltransferase-1 and cell death
inducing DFFA-like effector-a were up-regulated in WAT of the 5X group. Moreover,
L. reuteri 263 might induce browning of WAT due to the higher mRNA levels of
browning-related genes peroxisome proliferator-activated receptor-gamma, PR
domain containing-16, Ppargamma coactivator-1alpha, bone morphogenetic protein-7
and fibroblast growth factor-21 in the 1X and 5X groups compared to the HE group.
Finally, L. reuteri 263 altered the expressions of genes involved in glucose and
lipid metabolisms in WAT, including increasing the levels of glucose transporter
type 4 and carbohydrate-responsive element-binding protein and decreasing the
expression of Acetyl-CoA carboxylase-1. The results suggest that L. reuteri 263
may treat obesity through energy metabolism remodeling of WAT in the high-energy
diet-induced obese rats.
PMID- 29329014
TI - Nanoadsorbents based on conducting polymer nanocomposites with main focus on
polyaniline and its derivatives for removal of heavy metal ions/dyes: A review.
AB - Water contamination by toxic heavy metal ions and dyes remains a serious public
health problem for humans, so attention on specific methods and technologies to
remove heavy metal ions and dyes from wastewaters/aqueous solutions are desired.
Numerous adsorbents have been reported for the removal of heavy metal ions/dyes
from wastewaters/aqueous solutions. Polyaniline (PANI) and its derivatives, as
conducting polymers, are good adsorbents to remove various kinds of heavy metal
ions and dyes from wastewaters/aqueous solutions. The nanoadsorbents based on
PANI and its derivatives have received much consideration, and are extensively
reported in literature. This review focuses on the PANI and its derivatives based
on nanoadsorbents for water purification. Various types of these nanoadsorbents
used for the removal of heavy metal ions/dyes from wastewaters/aqueous solutions
are also briefly compared in this review.
PMID- 29329015
TI - Modelling of road traffic fatalities in India.
AB - Passenger modes in India include walking, cycling, buses, trains, intermediate
public transport modes (IPT) such as three-wheeled auto rickshaws or tuk-tuks,
motorised two-wheelers (2W) as well as cars. However, epidemiological studies of
traffic crashes in India have been limited in their approach to account for the
exposure of these road users. In 2011, for the first time, census in India
reported travel distance and mode of travel for workers. A Poisson-lognormal
mixture regression model is developed at the state level to explore the
relationship of road deaths of all the road users with commute travel distance by
different on-road modes. The model controlled for diesel consumption (proxy for
freight traffic), length of national highways, proportion of population in urban
areas, and built-up population density. The results show that walking, cycling
and, interestingly, IPT are associated with lower risk of road deaths, while 2W,
car and bus are associated with higher risk. Promotion of IPT has twofold
benefits of increasing safety as well as providing a sustainable mode of
transport. The mode shift scenarios show that, for similar mode shift across the
states, the resulting trends in road deaths are highly dependent on the baseline
mode shares. The most worrying trend is the steep growth of death burden
resulting from mode shift of walking and cycling to 2W. While the paper
illustrates a limited set of mode shift scenarios involving two modes at a time,
the model can be applied to assess safety impacts resulting from a more complex
set of scenarios.
PMID- 29329016
TI - Non-linear effects of the built environment on automobile-involved pedestrian
crash frequency: A machine learning approach.
AB - Although a growing body of literature focuses on the relationship between the
built environment and pedestrian crashes, limited evidence is provided about the
relative importance of many built environment attributes by accounting for their
mutual interaction effects and their non-linear effects on automobile-involved
pedestrian crashes. This study adopts the approach of Multiple Additive Poisson
Regression Trees (MAPRT) to fill such gaps using pedestrian collision data
collected from Seattle, Washington. Traffic analysis zones are chosen as the
analytical unit. The effects of various factors on pedestrian crash frequency
investigated include characteristics the of road network, street elements, land
use patterns, and traffic demand. Density and the degree of mixed land use have
major effects on pedestrian crash frequency, accounting for approximately 66% of
the effects in total. More importantly, some factors show clear non-linear
relationships with pedestrian crash frequency, challenging the linearity
assumption commonly used in existing studies which employ statistical models.
With various accurately identified non-linear relationships between the built
environment and pedestrian crashes, this study suggests local agencies to adopt
geo-spatial differentiated policies to establish a safe walking environment.
These findings, especially the effective ranges of the built environment, provide
evidence to support for transport and land use planning, policy recommendations,
and road safety programs.
PMID- 29329017
TI - Amiodarone, a multi-channel blocker, enhances anticonvulsive effect of
carbamazepine in the mouse maximal electroshock model.
AB - Cardiac arrhythmia may occur in the course of epilepsy. Simultaneous therapy of
the two diseases might be complicated by drug interactions since antiarrhythmic
and antiepileptic agents share some molecular targets. The aim of this study was
to evaluate the influence of amiodarone, an antiarrhythmic drug working as a
multi-channel blocker, on the protective activity of four classical antiepileptic
drugs in the maximal electroshock test in mice. Amiodarone at doses up to 75
mg/kg did not affect the electroconvulsive threshold in mice. Acute amiodarone at
the dose of 75 mg/kg significantly potentiated the anticonvulsive effect of
carbamazepine, but not that of valproate, phenytoin or phenobarbital in the
maximal electroshock-induced seizures in mice. The antiarrhythmic agent and its
combinations with antiepileptic drugs did not impair motor performance or long
term memory in mice, except for the combination of amiodarone and phenobarbital.
Brain concentrations of antiepileptic drugs were not changed. Despite favourable
impact of amiodarone on the anticonvulsive action of carbamazepine in the maximal
electroshock, co-administration of the two drugs should be carefully monitored in
clinical conditions. Further studies are necessary to evaluate effects of chronic
treatment with amiodarone on seizure activity and the action of antiepileptic
drugs.
PMID- 29329019
TI - Salidroside influences the cellular cross-talk of human fetal lung diploid
fibroblasts: A proteomic approach.
AB - Senescence is a complex multiple factor proces, which is still poorly understood.
The purpose of this study was to find the proteome of cultured human fetal lung
diploid fibroblasts (2BS) of different population doubling (PD), as well as the
altered proteome induced by salidroside (SAL) in 2BS cells. Proteins were
identified by two-dimensional electrophoresis (2-DE) combining matrix-assisted
laser desorption/ionization-time and flight mass spectrometry (MAL DI-TOF/MS). As
a result, we found 16 proteins with two-fold variations in senescent cells or
after SAL treatment, some being reduced such as reticulocalbin-1, heat shock
protein beta-6, elongation factor 1-delta, F-actin-capping protein subunit alpha
1, and chloride intracellular channel 1. In contrast, 40S ribosomal protein SA,
proteasome subunit alpha type-5, and zinc finger BED domain-containing protein 5
increased with cell age. Furthermore, heat shock protein beta-6, Zinc finger BED
domain-containing protein 5 was increased in PD30 cells after 10 MUM SAL
treatment, whereas, elongation factor 1-delta, 6-phosphogluconolactonase,
Nucleoside diphosphate kinase A, F-actin-capping protein subunit alpha-1,
Probable ATP-dependent RNA helicase DDX41, Chloride intracellular channel 1, and
Peroxiredoxin-6 were increased in PD50 cells after 10 MUM SAL treatment. Some of
these proteins were involved in the protein synthetic and degradative pathways,
which emphasizes the metabolic disorder or functional impairment of cell
senescence. Moreover, these proteins could be candidate biomarkers for evaluating
the SAL anti-senescence effect.
PMID- 29329018
TI - Corrosion effect of Bacillus cereus on X80 pipeline steel in a Beijing soil
environment.
AB - The corrosion of X80 pipeline steel in the presence of Bacillus cereus (B.
cereus) was studied through electrochemical and surface analyses and live/dead
staining. Scanning electron microscopy and live/dead straining results showed
that a number of B. cereus adhered to the X80 steel. Electrochemical impedance
spectroscopy showed that B. cereus could accelerate the corrosion of X80 steel.
In addition, surface morphology observations indicated that B. cereus could
accelerate pitting corrosion in X80 steel. The depth of the largest pits due to
B. cereus was approximately 11.23MUm. Many pits were found on the U-shaped bents
and cracks formed under stress after 60days of immersion in the presence of B.
cereus. These indicate that pitting corrosion can be accelerated by B. cereus. X
ray photoelectron spectroscopy results revealed that NH4+ existed on the surface
of X80 steel. B. cereus is a type of nitrate-reducing bacteria and hence the
corrosion mechanism of B. cereus may involve nitrate reduction on the X80 steel.
PMID- 29329020
TI - A novel mouse model of atopic dermatitis that is T helper 2 (Th2)-polarized by an
epicutaneous allergen.
AB - The pathogenesis of atopic dermatitis (AD) involves T helper 2 (Th2) cells, and
effective therapies remain elusive due to the paucity of animal models. We aimed
to develop a mouse model of an immune system aberration caused by allergen.
Experiments were conducted in two phases. In experiment 1, BALB/c mice were
sensitized with one of four chemical allergens - toluene diisocyanate (TDI),
hexamethylene diisocyanate (HDI), trimellitic anhydride (TMA), or 2,4
dinitrochlorobenzene (DNCB) - for 3 weeks. Based on results of experiment 1,
immunological features were compared between TMA-sensitized BALB/c mice and
NC/Nga mice, after exposure to mite extracts, harmful chemicals and detergents in
experiment 2. Sensitization by allergen caused a large number of pathological
changes in the skin, and an increase in mast cell number. TMA-sensitized BALB/c
mice models showed higher sensitivity to an environmental allergen than NC/Nga
mice did. Overall, the initial sensitization with TMA leads to disturbances in
Th2-mediated immunity.
PMID- 29329021
TI - Genotoxicity analysis of five particle matter toxicants from cigarette smoke
based on gammaH2AX assay combined with Hill/Two-component model.
AB - To investigate the genotoxic characteristics of typical toxicants in particle
phase of cigarette smoke, including B[a]P, nicotine, tar, NNN and NNK. The in
vitro gammaH2AX assay was used to detect the DNA double-strand breaks (DSBs) in
A549 cells using high content screening (HCS). The results showed all toxicants
had a dose/time-dependent effects on induction of gammaH2AX except for NNN and
NNK. Based on dose-response of gammaH2AX and Hill model, the ability to induce
DSBs was evaluated: NNN-acetate > B[a]P > NNK-acetate > tar > nicotine. Based on
time-course of gammaH2AX and two-component model, the complex DNA damage was the
main subtypes of DNA damage induced by these toxicants. Overall, all toxicants
were genotoxic in A549 cells in a dose- or time- dependent manner except for NNN
and NNK based on the gammaH2AX HCS assay. NNN-acetate had more potential to
induce DSBs, which was followed by B[a]P, NNK-acetate, tar and nicotine.
PMID- 29329022
TI - Impact of non-anticoagulant therapy on patients with sepsis-induced disseminated
intravascular coagulation: A multicenter, case-control study.
AB - INTRODUCTION: Anticoagulant therapy for patients with sepsis is not recommended
in the latest Surviving Sepsis Campaign guidelines, and non-anticoagulant therapy
is the global standard treatment approach at present. We aimed at elucidating the
effect of non-anticoagulant therapy on patients with sepsis-induced disseminated
intravascular coagulation (DIC), as evidence on this topic has remained
inconclusive. MATERIALS AND METHODS: Data from 3195 consecutive adult patients
admitted to 42 intensive care units for the treatment of severe sepsis were
retrospectively analyzed via propensity score analyses with and without multiple
imputation. The primary outcome was in-hospital all-cause mortality. RESULTS:
Among 1784 patients with sepsis-induced DIC, 745 (41.8%) were not treated with
anticoagulants. The inverse probability of treatment-weighted (with and without
multiple imputation) and quintile-stratified propensity score analyses (without
multiple imputation) indicated a significant association between non
anticoagulant therapy and higher in-hospital all-cause mortality (odds ratio [95%
confidence interval]: 1.59 [1.19-2.12], 1.32 [1.02-1.81], and 1.32 [1.03-1.69],
respectively). However, quintile-stratified propensity score analyses with
multiple imputation and propensity score matching analysis with and without
multiple imputation did not show this association. Survival duration was not
significantly different between patients in the propensity score-matched non
anticoagulant therapy group and those in the anticoagulant therapy group (Cox
regression analysis with and without multiple imputation: hazard ratio [95%
confidence interval]: 1.26 [1.00-1.60] and 1.22 [0.93-1.59], respectively).
CONCLUSIONS: It remains controversial if non-anticoagulant therapy is harmful,
equivalent, or beneficial compared with anticoagulant therapy in the treatment of
patients with sepsis-induced DIC.
PMID- 29329023
TI - Women's experiences with using a smartphone app (the Pregnant+ app) to manage
gestational diabetes mellitus in a randomised controlled trial.
AB - OBJECTIVE: The purpose of this study was to explore the experiences of women with
gestational diabetes mellitus (GDM) with controlling their blood glucose values
and receiving health and nutrition information using a smartphone app (the
Pregnant+ app). DESIGN AND PARTICIPANTS: The study utilised the interpretative
phenomenological analysis method. Semi-structured interviews were conducted with
17 participants among those participating to the randomised controlled trial.
RESULTS: The women experienced sorrow and disappointment when they were diagnosed
with GDM, but they all went through a process of learning to self-manage their
condition that was strongly motivated by theirdesire to care for their unborn
babies. The women found that the app increased their confidence in their self
management of GDM and their motivation for behavioural change. For some women,
the app contributed to feelings offrustration or obsession. In addition, some
technological problems and a lack of support from health-care professionals
limited several women from using the app. KEY CONCLUSIONS AND IMPLICATIONS FOR
PRACTISE: The findings suggest that asmartphone app may have potential for
supporting women with GDM, particularly in their blood glucose management.
However, it also highlights some of the potential challenges of using mHealth
technologies. The findings indicate that a closer collaboration between health
care professionals and patients is of great importance in the implementation of
apps for women with GDM.
PMID- 29329024
TI - 'TeamUP': An approach to developing teamwork skills in undergraduate midwifery
students.
AB - OBJECTIVE: to develop an effective model to enable educators to teach, develop
and assess the development of midwifery students' teamwork skills DESIGN: an
action research project involving participant interviews and academic feedback.
SETTING: a regional university PARTICIPANTS: midwifery students (n = 21) and new
graduate midwives (n = 20) INTERVENTIONS: a whole of course program using a
rubric, with five teamwork domains and behavioural descriptors, to provide a
framework for teaching and assessment. Students self and peer assess. Lectures,
tutorials and eight different groupwork assignments of increasing difficulty,
spread over the three years of the undergraduate degree are incorporated into the
TeamUP model. FINDINGS: the assignments provide students with the opportunity to
practice and develop their teamwork skills in a safe, supported environment. KEY
CONCLUSIONS: the social, emotional and practical behaviours required for
effective teamwork can be taught and developed in undergraduate health students.
IMPLICATIONS FOR PRACTICE: students require a clear overview of the TeamUP model
at the beginning of the degree. They need to be informed of the skills and
behaviours that the TeamUP model is designed to help develop and why they are
important. The success of the model depends upon the educator's commitment to
supporting students to learn teamwork skills.
PMID- 29329025
TI - The Midwifery Services Framework: The process of implementation.
AB - In 2015, the International Confederation of Midwives launched the Midwifery
Services Framework: a new evidence-based tool to guide countries through the
process of improving their sexual, reproductive, maternal and newborn health
services through strengthening and developing the midwifery workforce. The
Midwifery Services Framework is aligned with key global architecture for sexual,
reproductive, maternal and newborn health and human resources for health, and
with the recommendations of the 2014 Lancet Series on Midwifery. This second in a
series of three papers describes the process of implementing the Midwifery
Services Framework: the preparatory work, what happens at each stage of
implementation and who should be involved at each stage. It gives an idea of the
scale of the task, and the resources that will be required to implement the
Midwifery Services Framework in a given country context. The paper will be of
interest to health policy-makers, development partners and professional
associations in countries considering different approaches to strengthening their
sexual, reproductive, maternal and newborn health services, and it will help them
to decide whether and when either full or partial/staged implementation of the
Midwifery Services Framework will be an appropriate initiative to address
identified deficits in their specific context, given the current and projected
availability of resources.
PMID- 29329026
TI - The interaction of pyridoxal isonicotinoyl hydrazone (PIH) and salicylaldehyde
isonicotinoyl hydrazone (SIH) with iron.
AB - The interaction of pyridoxal isonicotinoyl hydrazone (PIH) and salicylaldehyde
isonicotinoyl hydrazone (SIH), two important biologically active chelators, with
iron has been investigated by spectrophotometric methods. High iron(III) affinity
constants were determined for PIH, logbeta2=37.0 and SIH, logbeta2=37.6. The
associated redox potentials of the iron complexes were determined using cyclic
voltammetry at pH7.4 as +130mV (vs normal hydrogen electrode, NHE) for PIH and
+136mV(vs NHE) for SIH. These redox potentials are much higher than those
corresponding to iron chelators in clinical use, namely deferiprone, -620mV;
desferasirox, -600mV and desferrioxamine, -468mV. Although the positive redox
potentials of SIH and PIH are similar to that of EDTA, namely +120mV, the iron
complexes of these two hydrazone chelators, unlike the iron complex of EDTA, do
not redox cycle in the presence of vitamin C. These properties render PIH and SIH
as excellent scavengers of iron, under biological conditions. Both SIH and PIH
scavenge mononuclear iron(II) and iron(III) rapidly. These fast kinetic
properties of the hydrazone-based chelators provide a ready explanation for the
adoption of SIH in fluorescence-based methods for the quantification of cytosolic
iron(II).
PMID- 29329027
TI - Cytotoxic and anticancer properties of new ruthenium polypyridyl complexes with
different lipophilicities.
AB - Three ruthenium complexes containing a bidentate piq ligand, [(piq)Ru(bpy)2]2+
(1), [(piq)Ru(phen)2]2+ (2), and [(piq)Ru(DIP)2]2+ (3) (piq =
phenylisoquinolinate, bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, DIP =
4,7-diphenyl-1,10-phenanthroline), were prepared. The DNA binding properties of
complexes 1-3 to double-stranded DNA were studied. The binding of 1-3 to calf
thymus DNA (ct-DNA) yielded lower emission intensities than those observed with
the corresponding Ru complexes alone. To explore potential interactions of
complexes 1-3 with lipid-rich organs in live cells, the emission properties of
the Ru probes were studied with liposomes. The emission intensities of complexes
1-3 were enhanced to similar extents upon interaction with liposomes. The
cytotoxic activities of the complexes against MDA-MB-231 and HUVECs were
evaluated in vitro. The effects of complexes 1-3 on the survival of MDA-MB-231
cells were examined and compared with that of cis-platin. Complexes 2 and 3 were
more cytotoxic to cancer cells than cis-platin. Complexes 1-3 showed cellular
uptakes of 1.1, 10.6, and 76.6%, respectively, indicating that the greatest
amount of complex 3 entered the cancer cells. Inhibition of cell migration by
complexes 1-3 was also evaluated by the wound healing assay.
PMID- 29329028
TI - Equine allogeneic chondrogenic induced mesenchymal stem cells: A GCP target
animal safety and biodistribution study.
AB - The safety of the intra-articular use of mesenchymal stem cells (MSCs) is
scarcely reported. Therefore, the goal of this study was to investigate the
safety of a single intra-articular injection with allogeneic chondrogenic induced
MSCs combined with equine plasma (=the investigational product: IVP) compared to
a saline (0.9% NaCl) placebo control (=control product: CP). Sixteen healthy
experimental horses were randomly assigned to receive a single intra-articular
injection with either the IVP (n=8) or the CP (n=8) in the left
metacarpophalangeal joint. All horses underwent a daily clinical assessment
throughout the entire study period of 42days to assess adverse events.
Additionally, a local joint assessment and a lameness examination were performed
daily during the first two weeks, and weekly the following 4weeks. Blood samples
were taken weekly for hematological and biochemical analysis. At the end of the
study period, horses of the IVP group were euthanized for a thorough necropsy and
to check for biodistribution. Tissue samples of the injected joint were collected
for histological examination. In both CP and IVP treated horses a mild transient
subjective increase in periarticular temperature and lameness was noted after the
intra-articular injection with no significant differences between the treatment
groups. No distribution of the cells was found using immunohistochemistry and no
ectopic tissue formation or signs of inflammation were found on histology. A
single intra-articular injection of allogeneic chondrogenic induced MSCs combined
with allogeneic plasma in horses had the same clinical side effects as an intra
articular injection with saline solution.
PMID- 29329029
TI - Corrigendum to "Pharmacological profile of dexketoprofen in orofacial pain"
[Pharmacol. Rep. 68 (6) (2016) 1111-1114].
PMID- 29329030
TI - pDok2, caspase 3 dependent glioma cell growth arrest by nitidine chloride.
AB - BACKGROUND: Nitidine chloride (NC) is known to exert anticancer and anti
metastatic effects on a variety of tumors. Recently, NC has also been shown to
inhibit PIK3/AKT/mTOR axis in U87 human glioma cells. METHODS: The study shows NC
employing pDok2, caspase 3 dependent cell death in C6 rat glioma and U87 human
malignant glioblastoma cells. The effect of NC on glioblastoma cell lines was
accessed by MTT, clonogenic and wound healing assays. Cell cycle analysis was
performed by FACS. Moreover, the effect of NC on downstream target proteins, such
as caspase3, pDok2, PARP, and Gsk3 beta, were measured by western blotting.
RESULTS: Overexpressed pDok2 protein has recently been reported as a prognostic
marker with poor outcomes for human glioblastoma multiformae. We found that NC
inhibits pDok2 in U87 cells in a concentration-dependent way. We further showed
that cleaved PARP and cleaved caspase 3 protein expressions were increased in C6
cells treated with NC in a dose-dependent way. NC effectively attenuated C6 cells
growth and colony formation at 8MUM (micromoles) concentration. Cell cycle arrest
in G2/M phase was further confirmed by flow cytometry. NC also exhibited its
inhibitory effect on Gsk3 beta, which has been proven to be altered in glioma
biology. CONCLUSIONS: Collectively, we predicted that NC could be employed as a
potential anti-glioma mediator that needs attention to explore the mechanisms of
its activity.
PMID- 29329031
TI - Development of a new ex vivo model for evaluation of endoscopic submucosal
injection materials performance.
AB - BACKGROUND AND AIMS: Development of high-performance submucosal injection
materials (SIMs) contribute to the advancement of endoscopic therapy for early
stage gastrointestinal neoplasms. This study aimed to develop a new ex vivo model
that mimics the human gastrointestinal tract to evaluate the performance (the
height and duration of the submucosal elevation) of various SIMs in detail.
METHODS: A new ex vivo model that applies a constant tension to the tested
specimen (the porcine gastric specimen) was developed. SIMs were injected into
the submucosa at the center or edge of the tested specimen, and submucosal
elevation heights (SEHs) were measured over time. RESULTS: The average value and
standard deviation of SEH determined using the conventional model (the tested
specimen was fixed with pins) were higher than those obtained using the new
model, which showed that the new model could precisely measure the SEH of a given
SIM. In addition, the performance (SEH) of SIMs decreased with increasing tension
applied to the specimen, suggesting that the performance of SIMs deteriorates
with the over-expansion of the gastrointestinal tract. The submucosal elevation
formed at the specimen edge disappeared faster than that formed at the specimen's
center. CONCLUSIONS: The proposed new ex vivo model allows accurate SEH
measurement under uniform conditions and detailed comparison of the performances
of various types of SIMs and can contribute to the development of high
performance materials.
PMID- 29329032
TI - Targeting expression of adenosine receptors during hypoxia induced angiogenesis -
A study using zebrafish model.
AB - Hypoxia is known to be a major player during pathological angiogenesis and
adenosine as a negative feedback signaling to maintain oxygen delivery in
pathological ischemic condition. We mimicked hypoxic condition and studied
angiogenesis by inducing adenosine receptors using forskolin, a plant compound
and NECA analogue of adenosine using zebrafish model. Vascular endothelial growth
factor (VEGF) is known to play a key role during pathological angiogenesis and
regulated by the factors HIF1a under hypoxic condition and recently Notch is
proposed to play a negative feedback loop mechanism along with VEGF signaling but
the role of adenosine receptor during the process is not known. We evaluated the
mRNA expression of adenosine receptors (A1, A2a.1, A2a.2, A2b), HIF1a, VEGF A,
VEGF R2, NRP1a, NOTCH 1a and DLL4 and the phenotypic variations of zebrafish
embryos when treated with DAPT, gamma-secretase inhibitor of Notch in addition to
treating the embryos with SU5416, a VEGF receptor inhibitor. Upregulation of
adenosine receptors (A1, A2a.1, A2a.2, A2b), HIF1a, VEGF A, VEGF R2, NRP1a,
NOTCH1a and DLL4 was observed embryos were when treated with forskolin and NECA
could possibly mimic hypoxic condition. Hatching and heart rate also increased
with NECA and forskolin. SU5416 showed decreases in blood vessel formation and
decreased adenosine receptors, VEGF, VEGFR2, HIF1a and NRP1a expression and DAPT,
exhibited decreases in blood vessels and decreased NRP1a, NOTCH1a, DLL4
expression. These embryos developed with poor vasculature, tail bending, abnormal
phenotypes and developmental delay. Forskolin treated with inhibitors showed
increased blood vessel formation, normal phenotype, development and adenosine
receptors (A1, A2a.1, A2a.2, A2b), HIF1a, VEGF A, VEGF R2, NRP1a, NOTCH 1a and
DLL4 gene expression suggesting that adenosine mediated Notch and VEGF could play
an important role during development and angiogenesis. Targeting VEGF and Notch
signaling with adenosine receptors inhibitors which might have a therapeutic
significance during hypoxia and abnormal angiogenesis.
PMID- 29329033
TI - Onjisaponin B prevents cognitive impairment in a rat model of D-galactose-induced
aging.
AB - In this study, we investigated the potential effect of onjisaponin B (OB) on
aging rats induced by D-gal (D-galactose). Sub-acute aging model was established
in rats by the subcutaneous injection of D-gal (120 mg/kg) for 42 days,
accompanied with OB (10, 20 mg/kg, p.o.) or normal saline intervention for 28
days since the 14th day after the beginning of D-gal stimulation. Morris water
maze test and step-down passive avoidance test were conducted to evaluate the
cognitive function of the rats. The superoxidase dismutase (SOD), malondialdehyde
(MDA), glutathione (GSH) and glutathione peroxidase (GSH-px) contents in
hippocampus were measured by according kits, respectively. And the hippocampus
levels of inflammatory mediators including tumor necrosis factor-alpha (TNF
alpha), interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) were assayed by
enzyme-linked immunosorbent assay (ELISA). Furthermore, the expressions of SOD1,
MDA5, GSH, GSH-px, NF-kB pathway were present by western blot. It revealed that
administration of OB was able to significantly attenuate the D-gal-induced
changes in the hippocampus, ranging from cognitive capacity, oxidative stress to
inflammation response. In a nutshell, our data provided evidence that OB could
contribute to the restoration of cognitive ability by improving the antioxidant
and anti-inflammatory capacity in D-gal induced aging rats.
PMID- 29329034
TI - Long non-coding RNA CCAT2 promotes cholangiocarcinoma cells migration and
invasion by induction of epithelial-to-mesenchymal transition.
AB - Cholangiocarcinoma (CCA) is one of the most aggressive malignancies in humans.
Emerging evidence has indicated that abnormally expressed long non-coding RNAs
(lncRNAs) could conduce to tumorigenesis and progression. Specifically, colon
cancer-associated transcript 2 (CCAT2) has been reported to be overexpressed in
several carcinomas. However, its clinical significance and functional roles in
CCA is still unknown. qRT-PCR experiments were conducted to assess the CCAT2
expression in CCA tissue samples and cell lines. In addition, the link between
CCAT2 expression and clinicopathological characteristics was analyzed. The
potential effects of CCAT2 in CCA cells was evaluated in vitro including cell
proliferation, colony-forming ability, apoptosis, migration, invasion and
epithelial-to-mesenchymal transition (EMT). As a result, CCAT2 was aberrantly
overexpressed in CCA tissue samples and cells, and this upregulation was
correlated with tumor size, lymph node invasion, TNM stage and postoperative
recurrence in CCA patients. Overexpression of CCAT2 could serve as an independent
prognostic indicator for CCA. Additionally, overexpression of CCAT2 was a dismal
prognostic indicator for patients with CCA. Furthermore, CCAT2 silencing caused
tumor suppressive effects via reducing cell proliferation, migration and
invasion, inducing cell apoptosis and reversing the EMT process in HuCCT1 and
CCLP1 cells. Collectively, our data illustrated that lncRNA CCAT2 played an
oncogenic role in CCA and may offer a potential therapeutic target for treating
this fatal disease.
PMID- 29329035
TI - Esterification of trans-aconitic acid improves its anti-inflammatory activity in
LPS-induced acute arthritis.
AB - trans-Aconitic acid (TAA) is an abundant constituent in the leaves of Echinodorus
grandiflorus, a medicinal plant used to treat rheumatoid arthritis in Brazil.
Esterification was explored as a strategy to increase lipophilicity and
biopharmaceutical properties of TAA, a highly polar tricarboxylic acid. We herein
report the synthesis of TAA esters via Fischer esterification with ethanol, n
butanol and n-octanol. The reaction kinetics was investigated to produce mono-,
di- and tri- derivatives. Mono- and diesters of TAA were obtained as a mixture of
positional isomers, whereas the triesters were recovered as pure compounds. The
obtained esters were screened in a model of acute arthritis induced by the
injection of LPS in the knee joint of Swiss mice. The diesters were the most
active compounds, regardless of the alcohol employed in the reaction, whereas
bioactivity of the derivatives improved by increasing the length of the aliphatic
chain of the alcohol employed in esterification. In general, the esters showed
higher potency than TAA. When administered orally to mice at doses of 0.017-172.3
MUmol/Kg, the diethyl, di-n-butyl and di-n-octyl esters of TAA reduced the
cellular infiltration into the knee joint, especially of neutrophils. The study
identified diesters of TAA as potential useful derivatives for the management of
rheumatoid arthritis and other inflammatory diseases.
PMID- 29329036
TI - Crocin improves the proliferation and cytotoxic function of T cells in children
with acute lymphoblastic leukemia.
AB - OBJECTIVE: Immunotherapy is important to improve the survival of children with
acute lymphoblastic leukemia (ALL). This study aimed to assess the effects of
crocin on the proliferation and function of T cells isolated from children with
ALL. METHODS: The mononuclear cells were isolated from peripheral blood of
children with ALL and then treated with different final concentrations of crocin.
The levels of different cytokines secreted by T cells and the ratio of CD4 and
CD8 were measured. Tail DNA% (TDNA), Tail moment (TM), Tail length (TL) and
sister chromatid exchange (SCE) were detected to assess DNA damage of T cells.
RESULTS: Crocin significantly promoted T cell proliferation and the secretion of
IL-2 and IL-4 in a concentration dependent manner. In addition, crocin increased
CD4/CD8 ratio of T subset. Crocin itself caused no significant damage to T cells
but reduced DNA damage in T cells treated with Ara-C. CONCLUSIONS: Crocin could
improve the proliferation and cytotoxic function of T cells, and reduce DNA
damage caused by Ara-C.
PMID- 29329037
TI - Phloem function: a key to understanding and manipulating plant responses to
rising atmospheric [CO2]?
AB - Increasing atmospheric carbon dioxide concentration ([CO2]) directly stimulates
photosynthesis and reduces stomatal conductance in C3 plants. Both of these
physiological effects have the potential to alter phloem function at elevated
[CO2]. Recent research has clearly established that photosynthetic capacity is
correlated to vascular traits associated with phloem loading and water transport,
but the effects of elevated [CO2] on these relationships are largely unexplored.
Plants also employ different strategies for loading sucrose and other sugars into
the phloem, and there is potential for species with different phloem loading
strategies to respond differently to elevated [CO2]. Recent research manipulating
sucrose transporters and other key enzymes with roles in phloem loading show
promise for maximizing crop performance in an elevated [CO2] world.
PMID- 29329038
TI - Hallucinations as a presenting complaint in emergency departments: Prevalence,
diagnosis, and costs.
AB - Hallucinations occur in the context of many disorders. When experienced as
distressing, they are a likely cause of presentation to emergency departments.
Knowledge about the rates, diagnoses, and associated costs of hallucinations in
emergency departments however is currently lacking. In this study, we analysed
patients' presenting complaints in Western Australia's Emergency Department Data
Collection dataset during a two year period (n = 1,798,754). Visits to emergency
departments because of distressing hallucinations were more common than
previously assumed. Hallucinations (auditory, visual, undifferentiated modality)
accounted for 1.8% of all mental health-related presentations and 0.09% of all
general health presentations (84.7 per 100,000 persons). Psychotic disorders
accounted for a third of all presentations, and hallucinations without a clear
medical or psychiatric cause represented 17% of the sample. Hallucination
presentations had significantly prolonged lengths of stay compared to other
mental health presentations (15 vs 7.5h, p < 0.001) and were linked to frequent
re-admissions (average of 7.4 visits per year). Cost estimates revealed that
hallucinations were in the top-10 most costly mental health complaint, and twice
as costly to treat as delusions. Altogether, the service utilisation and care
needs of people with distressing hallucinations outside of mental health services
appear much larger than usually estimated.
PMID- 29329039
TI - An investigation into the drivers of avolition in schizophrenia.
AB - Over a century of research has documented that avolition is a core symptom in
schizophrenia. However, the drivers of avolition remain unclear. Conceptually,
there are at least two potential mutually compatible drivers that could cause
avolition in schizophrenia. First, people with schizophrenia might have
differences in preferences that result in less goal-directed behavior than non
clinical populations (preference-differences). Second, people with schizophrenia
might have difficulty translating their preferences into manifest behavior at
rates similar to non-clinical populations (psychological-inertia). In the present
work, we modified and validated a well-validated paradigm from the
motivation/decision making literature to compare levels of preference-differences
and psychological-inertia. To measure preference-differences, people with and
without schizophrenia choose between a lower-valenced and higher-valenced image.
We measured the rate at which the normatively lower-valenced image was preferred.
To measure psychological-inertia, both groups were given the opportunity to
volitionally switch from a lower-valenced image and view a higher-valenced image.
Contrary to expectations, people with schizophrenia did not differ on either
preference-differences or psychological-inertia. Statistical analysis revealed
that the possibility of a Type II error for even a weak effect was small. The
present data suggest new avenues for research investigating mechanisms underlying
avolition and clinical interventions targeting avolition in schizophrenia.
PMID- 29329041
TI - Thiol/disulphide homeostasis in bipolar disorder.
AB - Bipolar disorder (BD) patients have increased oxidative stress, which can disturb
thiol/disulphide homeostasis, causing disulphide formation. The aim of the study
is to investigate dynamic thiol/disulphide (SH/SS) homeostasis in BD patients,
which is a novel evaluation method of oxidative status. Ninety-four BD patients
(50 in the manic episode and 44 in remission) and 44 healthy controls were
included in the study. Blood serum native thiol (SH) and total thiol (ToSH)
concentrations were measured in a paired test. The half value of the difference
between native thiol and total thiol concentrations was calculated as the
disulphide (SS) bond amount. Serum native thiol levels of the mania group were
found to be lower than the remission and the control groups. There was a
significant difference between the remission group and the control group in terms
of native thiol. Serum total thiol level was lower in mania group than the
control group. Detection of oxidative molecules for BD could be helpful,
especially in treatment, follow-up periods and reducing morbidity. The results of
our study besides the data available in the literature support that thiol and
disulphide levels are useful markers for BD and promising therapeutic targets in
terms of future pharmacological modulation.
PMID- 29329040
TI - Do adverse life events at first onset of auditory verbal hallucinations influence
subsequent voice characteristics? Results from an epidemiological study.
AB - Understanding what happens at first onset of auditory verbal hallucinations
(AVHs) is extremely important on a clinical and theoretical level. Previous
studies have only focused on age with regard to first onset of AVHs. In the
current epidemiological study, we examined a number of aspects relating to first
onset of AVHs, such as the role of adverse life events at first onset of AVHs on
symptom severity and general mental health. For this purpose, we compared
participants who reported adverse life events at first onset of AHVs (adverse
trigger group; N = 76) to those that did not report any specific events at first
onset of AVHs (no-adverse-trigger group; N = 59) on a large array of variables.
Results showed that AVHs in the adverse-trigger group were experienced as more
emotional compared to the no-adverse-trigger group. In addition, the adverse
trigger group more often reported hallucinations in other (non-auditory) sensory
modalities (e.g. visual) compared to the no-adverse-trigger group. Furthermore,
the adverse-trigger group reported poorer general mental health, reported having
contact with mental health professionals more often, and also reported more
frequently taking medication for psychological problems in general. The
implications of these findings are discussed.
PMID- 29329042
TI - Assessment of the efficacy of omega-3 fatty acids on metabolic and inflammatory
parameters in patients with schizophrenia taking clozapine and sodium valproate.
AB - Omega-3 fatty acid (FA) supplementation has been reported to improve several
cardio-metabolic risk factors. We aimed to assess the efficacy of omega-3 fatty
acids on metabolic and inflammatory indices in patients with schizophrenia who
were taking clozapine and sodium valproate. All patients were on a stable dose of
300-400mg of clozapine for 3 months. Subjects were randomized to treatment with
either omega-3 fatty acid (4gr/day) or a placebo for 8 weeks. Height, weight,
abdominal circumference, serum lipid profile, fasting blood glucose (FBG), and
serum high sensitivity-C-reactive protein (hs-CRP) were determined at baseline
and after 8 weeks of treatment. Fifty six subjects were recruited into the study.
Patients with schizophrenia who were in the group receiving omega-3 FA capsules
had an improvement in some anthropometric indices including weight, BMI, wrist
and waist circumference, compared to the placebo group. Only changes in waist
circumferences remained significantly different after adjustment for serum fasted
TG. Our results showed omega-3 FA supplementation can improve some anthropometric
indices in patients with schizophrenia who are taking clozapine pharmacotherapy.
PMID- 29329043
TI - Impact of synthetic cannabinoid use on hospital stay in patients with bipolar
disorder versus schizophrenia, or other psychotic disorders.
AB - Synthetic cannabinoid products have become popular and have led to an increased
number of patients presenting to emergency departments and psychiatric hospitals.
The purpose of this study was to evaluate the impact of synthetic cannabinoid use
at admission on length of stay and doses of antipsychotics at discharge in
individuals with bipolar disorder, schizophrenia and other psychotic disorders.
We retrospectively examined medical records of 324 inpatients admitted from
January 2014 to July 2015. We found that synthetic cannabinoid use predicted
length of stay and antipsychotic dose using structural equation modeling.
Further, the association of synthetic cannabinoid use with length of stay was
partly mediated by antipsychotic dose. These associations were independent of
specific diagnosis. In conclusion, patients with bipolar disorder, schizophrenia,
or other psychotic disorders who reported synthetic cannabinoid use at admission
had shorter length of stay and received lower doses of antipsychotics,
irrespective of clinical diagnoses.
PMID- 29329044
TI - Neurological soft signs in bipolar and unipolar disorder: A case-control study.
AB - Neuropsychiatric disorders are associated with neurological soft signs (NSS),
including motor, sensory, and inhibitory dysfunction. The present study aims at
determining the prevalence of NSS and explore the association of sociodemographic
characteristics with the occurrence of NSS in patients with bipolar disorder and
unipolar depression compared to healthy controls. A case-control study included a
sample of 50 bipolar and unipolar patients and 50 healthy controls. NSS subscales
of the Neurological Evaluation Scale (NES) were administered to each participant.
Significant differences were found in the total NES score, motor coordination,
sensory integration, sequence of complex motor act and other subscales among the
three groups. Compared with healthy controls, patients with bipolar disorder
showed significantly more total NSS signs, motor coordination signs and sensory
integration signs. When compared with patients with unipolar disorder, patients
with bipolar disorder showed significantly more sensory integration signs and a
trend of difference in the sequencing of complex motor acts and other subscales.
Our findings suggest that NSS may be specifically associated with bipolar
disorder but not unipolar depression. The specificity of NSS expression has the
potential to help the discrimination of bipolar disorder from disorders less
likely to have a neurodevelopmental component such as major depression.
PMID- 29329045
TI - Increased depression symptom score in newly diagnosed type 2 diabetes patients.
AB - The aim was to investigate the association between diabetes duration and
depressive symptoms in type 2 diabetes. The DIAREG registry used data of a
nationwide general medicine practice database (Disease Analyzer, Germany)
augmented by prospective data from patient reported outcomes (PRO) including
Center of Epidemiological Studies Depression Scale (CES-D: <16 vs. >=16) and the
SF-36. Multiple logistic regression models were used to investigate the
association of diabetes duration with PROs. Overall, 1807 type 2 diabetes
patients were registered in 108 practices. From 270 (15%) patients complete PRO
could be collected, which were similar with respect to age, sex, body mass index,
HbA1c, diabetes duration and treatment to patients with incomplete data
(p>=0.05). Patients with a longer diabetes duration (reference: <2 years)
displayed a significantly increased odds of having no indication of depression
(CES-D <16: 66%) (Odds Ratio, 95%CI: 2-<5 years: 5.9, 1.2-29.6; 5-<10 years: 6.2,
1.3-28.7; >=10 years: 5.6, 1.2-23.1), after adjusting for age, sex, BMI, diabetes
complications, antidepressants and glucose-lowering treatment. Patients with <2
years diabetes duration also exhibited a significantly decreased mean mental
component score (SF-36: <2 years: 50, 2-<5 years: 69). In type 2 diabetes with a
short duration an increased depressive symptom score was observed.
PMID- 29329046
TI - Social distance toward people with schizophrenia is associated with favorable
understanding and negative stereotype.
AB - Previous studies have suggested the consequence of mental health-related public
stigma: the problem of knowledge may develop into problem of attitude and
behaviour. However, this has not been directly explored in a longitudinal study.
As the secondary analysis from our previous randomized controlled trial (RCT) for
219 participants who completed the survey at the 12-month follow-up, we aimed to
investigate whether the knowledge and attitude components of stigma toward people
with schizophrenia affect each other. At baseline and at 12 months, three types
of stigma scales were measured: favorable understanding, negative stereotype, and
social distance toward people with schizophrenia. A structured equation model was
fitted to the trajectory of stigma scales taking into account the effect of the
other stigma components and the interventions. The results showed that greater
social distance toward people with schizophrenia at baseline was associated with
less favorable understanding and more negative stereotype at the 12-month follow
up. This was not in line with the existing consequences from the previous
studies; however, in line with the recent RCTs showing that social contact is the
most effective intervention to reduce stigma. Future observational studies with a
larger sample size are needed to clarify this relationship further.
PMID- 29329047
TI - The connection between subjective nearness-to-death and depressive symptoms: The
mediating role of meaning in life.
AB - Depression is characterized by a wide range of emotional, cognitive, and physical
symptoms. Two prominent features of depressive symptoms are a sense that life has
no meaning on the one hand, and that life is not worth living on the other hand.
In recent years, the subjective perception of how close one feels to his/her
death has gained importance as a significant factor associated with various
aspects of physical and psychological well-being. Thus, the current study
examined the connection between subjective nearness-to-death, meaning in life,
and depressive symptoms, and assessed whether meaning in life mediates the
connection between subjective nearness-to-death and depressive symptoms. Data was
collected from 268 participants between the ages of 28 and 74 (mean age = 46.75),
who completed measures of subjective nearness-to-death, meaning in life, and
depressive symptoms. Results yielded a significant positive connection between
subjective nearness-to-death and depressive symptoms, as well as a negative
connection between meaning in life and depressive symptoms. Moreover, meaning in
life was found to mediate the connection between subjective nearness-to-death and
depressive symptoms. Findings are discussed in light of the Terror Management
Theory, and potential clinical implications are suggested.
PMID- 29329048
TI - Characterizing anger-related affect in individuals with posttraumatic stress
disorder using ecological momentary assessment.
AB - This study employed secondary analyses of existing ecological momentary
assessment (EMA) data to characterize hostile and irritable affect in the day-to
day experience of 52 smokers with, and 65 smokers without, posttraumatic stress
disorder (PTSD). EMA monitoring occurred over a mean of 8.2 days, and
participants responded to an average of 2.8 random prompts/day. Analyses included
Wilcoxon rank sum tests of group differences, and path analyses of cross-lagged
multilevel models. Participants with PTSD endorsed a significantly higher
proportion of total EMA entries indicating hostile affect and irritable affect
than did individuals without PTSD. Cross-lagged analyses indicated that over a
period of hours, PTSD symptoms significantly predicted subsequent hostile and
irritable affect, but hostile and irritable affect did not predict subsequent
PTSD symptoms. Findings suggest that day-to-day exposure to PTSD-related trauma
cues may contribute to chronically elevated levels of anger-related affect. Such
heightened affective arousal may, in turn, underlie an increased risk for verbal
or physical aggression, as well as other health and quality-of-life related
impairments associated with PTSD. Clinical implications include conceptualizing
anger treatment in the broader context of trauma history and symptoms, and
specifically targeting physiological arousal and maladaptive hostile cognitions
triggered by trauma reminders in patients with PTSD.
PMID- 29329049
TI - The traumatized body: Long-term PTSD and its implications for the orientation
towards bodily signals.
AB - Orientation to bodily signals is defined as the way somatic sensations are
attended, perceived and interpreted. Research suggests that trauma exposure,
particularly the pathological reaction to trauma (i.e., PTSD), is associated with
catastrophic and frightful orientation to bodily signals. However, little is
known regarding the long-term ramifications of trauma exposure and PTSD for
orientation to bodily signals. Less is known regarding which PTSD symptom cluster
manifests in the 'somatic route' through which orientation to bodily signals is
altered. The current study examined the long-term implications of trauma and PTSD
trajectories on orientation to bodily signals. Fifty-nine ex-prisoners of war (ex
POWs) and 44 controls were assessed for PTSD along three time-points (18, 30 and
35 years post-war). Orientation to bodily signals (pain catastrophizing and
anxiety sensitivity-physical concerns) was assessed at T3. Participants with a
chronic PTSD trajectory had higher pain catastrophizing compared to participants
with no PTSD. PTSD symptom severity at T2 and T3 mediated the association between
captivity and orientation. Among PTSD symptom clusters, hyperarousal at two time
points and intrusion at three time-point mediated the association between
captivity and orientation. These findings allude to the cardinal role of long
term PTSD in the subjective experience of the body following trauma.
PMID- 29329050
TI - Factors influencing the severity of behavioral phenotype in autism spectrum
disorders: Implications for research.
AB - The phenotypic heterogeneity of Autism Spectrum Disorders (ASD) presents
particular research challenges in the assessment of symptom severity, while the
standardized Autism Diagnostic Observation Schedule (ADOS) scores present a
severity metric, namely calibrated severity scores (CSS) that are relatively
impervious to individual characteristics. To date, no studies have examined the
convergent validity of CSS in Chinese sample populations. The present study
investigated the validity of the ADOS-CSS using a sample of 321 children aged 2
18 years with ASD, and developed upon existing literature examining the influence
of non-ASD-specific characteristics on other types of measures including Autism
Diagnostic Interview-Revised (ADI-R), Social Responsiveness Scale (SRS), and
Vineland Adaptive Behavior Scales (VABS). As expected, the findings revealed that
the CSS were less influenced than ADOS-RAW scores by the demographic and
developmental-level variables. Moreover, compared to the ADOS-CSS, the ADI-R, SRS
and VABS were still strongly correlated with confounding factors, such as
chronological age, intelligence quotients, and language-level. The results of
this study corroborate the utilization of CSS as a more valid indicator of ASD
severity than raw scores from ADOS and other instruments.
PMID- 29329052
TI - Efficient and cost-effective generation of hepatocyte-like cells through
microparticle-mediated delivery of growth factors in a 3D culture of human
pluripotent stem cells.
AB - Biomedical application of human pluripotent stem cell-derived hepatocyte-like
cells (hPSC-HLCs) relies on efficient large-scale differentiation, which is
commonly performed by a suspension culture of three-dimensional (3D)
multicellular spheroids in bioreactors. However, this approach requires large
amounts of growth factors (GFs) and the need to overcome limited diffusional
transport posed by the inherent 3D structure of hPSC spheroids. Here, we have
hypothesized that localized delivery of GFs by incorporation of GF-laden
degradable polymeric microparticles (MPs) within the hPSC spheroids would
circumvent such limitations. In this study, GFs for hepatocytic differentiation
were encapsulated in gelatin-coated poly (l-lactic acid)/poly (DL-lactic-co
glycolic acid) (PLLA/PLGA) MPs which were subsequently incorporated into the hPSC
spheroids. Gene expression analyses demonstrated that MP delivery of the GFs
resulted in similar expression levels of hepatocytic markers despite the use of
10-fold less total GFs. The differentiated HLCs in the MP group exhibited
ultrastructure and functional characteristics comparable with the conventional
soluble GF group. The generated HLCs in the MP group were successfully engrafted
in an acute liver injury mouse model and maintained hepatocytic function after
implantation. These results suggested that sustained and localized delivery of
GFs using MPs might offer a novel approach towards scalable technologies for
hepatocytic differentiation and engineer a better 3D microenvironment for cells.
PMID- 29329051
TI - Non-genetic engineering of cytotoxic T cells to target IL-4 receptor enhances
tumor homing and therapeutic efficacy against melanoma.
AB - Adoptive transfer of cytotoxic T lymphocytes (CTLs) has been used as an
immunotherapy in melanoma. However, the tumor homing and therapeutic efficacy of
transferred CTLs against melanoma remain unsatisfactory. Interleukin-4 receptor
(IL-4R) is commonly up-regulated in tumors including melanoma. Here, we studied
whether IL-4R-targeted CTLs exhibit enhanced tumor homing and therapeutic
efficacy against melanoma. CTLs isolated from mice bearing melanomas were non
genetically engineered with IL4RPep-1, an IL-4R-binding peptide, using a membrane
anchor composed of dioleylphosphatidylethanolamine. Compared to control CTLs, IL
4R-targeted CTLs showed higher binding to melanoma cells and in vivo tumor
homing. They also exerted a more rapid and robust effector response, including
increased cytokine secretion and cytotoxicity against melanoma cells and enhanced
reprogramming of M2-type macrophages to M1-type macrophages. Moreover, IL-4R
targeted CTLs efficiently inhibited melanoma growth and reversed the
immunosuppressive tumor microenvironment. These results suggest that non
genetically engineered CTLs targeting IL-4R have potential as an adoptive T cell
therapy against melanoma.
PMID- 29329053
TI - Long Term Safety Area Tracking (LT-SAT) with online failure detection and
recovery for robotic minimally invasive surgery.
AB - Despite the benefits introduced by robotic systems in abdominal Minimally
Invasive Surgery (MIS), major complications can still affect the outcome of the
procedure, such as intra-operative bleeding. One of the causes is attributed to
accidental damages to arteries or veins by the surgical tools, and some of the
possible risk factors are related to the lack of sub-surface visibilty. Assistive
tools guiding the surgical gestures to prevent these kind of injuries would
represent a relevant step towards safer clinical procedures. However, it is still
challenging to develop computer vision systems able to fulfill the main
requirements: (i) long term robustness, (ii) adaptation to environment/object
variation and (iii) real time processing. The purpose of this paper is to develop
computer vision algorithms to robustly track soft tissue areas (Safety Area, SA),
defined intra-operatively by the surgeon based on the real-time endoscopic
images, or registered from a pre-operative surgical plan. We propose a framework
to combine an optical flow algorithm with a tracking-by-detection approach in
order to be robust against failures caused by: (i) partial occlusion, (ii) total
occlusion, (iii) SA out of the field of view, (iv) deformation, (v) illumination
changes, (vi) abrupt camera motion, (vii), blur and (viii) smoke. A Bayesian
inference-based approach is used to detect the failure of the tracker, based on
online context information. A Model Update Strategy (MUpS) is also proposed to
improve the SA re-detection after failures, taking into account the changes of
appearance of the SA model due to contact with instruments or image noise. The
performance of the algorithm was assessed on two datasets, representing ex-vivo
organs and in-vivo surgical scenarios. Results show that the proposed framework,
enhanced with MUpS, is capable of maintain high tracking performance for extended
periods of time ( ? 4 min - containing the aforementioned events) with high
precision (0.7) and recall (0.8) values, and with a recovery time after a failure
between 1 and 8 frames in the worst case.
PMID- 29329054
TI - Relationship between sedentary behavior and depression: A mediation analysis of
influential factors across the lifespan among 42,469 people in low- and middle
income countries.
AB - BACKGROUND: Sedentary behavior (SB) is associated with diabetes, cardiovascular
disease and low mood. There is a paucity of multi-national research investigating
SB and depression, particularly among low- and middle-income countries. This
study investigated the association between SB and depression, and factors which
influence this. METHODS: Cross-sectional data were analyzed from the World Health
Organization's Study on Global Ageing and Adult Health. Depression was based on
the Composite International Diagnostic Interview. The association between
depression and SB (self-report) was estimated by multivariable linear and
logistic regression analyses. Mediation analysis was used to identify influential
factors. RESULTS: A total of 42,469 individuals (50.1% female, mean 43.8 years)
were included. People with depression spent 25.6 (95%CI8.5-42.7) more daily
minutes in SB than non-depressed participants. This discrepancy was most notable
in adults aged >= 65y (35.6min more in those with depression). Overall, adjusting
for socio-demographics and country, depression was associated with a 1.94
(95%CI1.31-2.85) times higher odds for high SB (i.e., >= 8h/day). The largest
proportion of the SB-depression relationship was explained by mobility
limitations (49.9%), followed by impairments in sleep/energy (43.4%),
pain/discomfort (31.1%), anxiety (30.0%), disability (25.6%), cognition (16.1%),
and problems with vision (11.0%). Other health behaviors (physical activity,
alcohol consumption, smoking), body mass index, and social cohesion did not
influence the SB-depression relationship. CONCLUSION: People with depression are
at increased risk of engaging in high levels of SB. This first multi-national
study offers potentially valuable insight for a number of hypotheses which may
influence this relationship, although testing with longitudinal studies is
needed.
PMID- 29329055
TI - Altered brain structure in women with premenstrual syndrome.
AB - BACKGROUND: Functional brain abnormalities have been noted in premenstrual
syndrome (PMS). However, the brain structural alterations related to PMS remain
unclear. This study aimed to identify possible abnormalities in gray matter (GM)
volumes and structural covariance patterns among PMS patients. METHODS:
Structural magnetic resonance imaging data were obtained from 20 PMS patients and
20 healthy controls. Voxel-based morphometry (VBM) analysis was applied to
examine GM volumes changes between the two groups. Receiver operating
characteristic (ROC) curve was used to investigate the most reliable biomarker
for distinguishing PMS patients from health controls based on the intergroup
differences. Correlation analysis was then performed to assess relationships
between the daily rating of severity of problems (DRSP) and abnormal brain
regions. Finally, the regions identified from VBM analysis were served as seeds
to characterize the whole-brain structural covariance patterns. RESULTS: Compared
with healthy controls, PMS patients showed increased GM volumes in the
precuneus/posterior cingulate cortex (precuneus/PCC) and thalamus, and decreased
GM volumes in the insula. The precuneus/PCC exhibited the highest classification
power by ROC analysis and positively correlated with the DRSP. Moreover,
different patterns of structural covariance in the two groups were mainly located
in the dorsolateral prefrontal cortex, anterior cingulate cortex, angular gyrus
and hippocampus. LIMITATIONS: This study is limited by a small sample and narrow
age range of participants. CONCLUSIONS: Our findings may provide preliminary
evidence for brain morphology alterations in PMS patients and contribute to a
better understanding of the pathophysiology of PMS.
PMID- 29329056
TI - Subjective and objective sleep discrepancy in symptomatic bipolar disorder
compared to healthy controls.
AB - BACKGROUND: Bipolar disorder (BD) is associated with sleep misperception. The
objective of this study was to investigate the correlation between subjective and
objective measures of sleep in persons with symptomatic bipolar disorder (BDS)
compared to healthy controls (HC). METHODS: We studied 24 BDS and 30 HC subjects
similar in age, race and sex. Subjective sleep was measured with Pittsburgh Sleep
Quality Index (PSQI) and objective sleep with 7-days of actigraphy. Absolute
discrepancy variables were calculated by subtracting objective sleep latency (SL)
and total sleep time (TST) on actigraphy from their respective subjective
estimates from PSQI. Mood symptoms were measured with Young Mania Rating Scale
and Hamilton Depression Rating Scale. RESULTS: In the BDS group, subjective TST
did not significantly correlate with objective TST, while it correlated in the HC
group. The BDS group had significantly higher absolute discrepancy between
subjective and objective SL and TST compared to the HC group. Multivariable
regression analysis showed that severity of depression was associated with
greater absolute discrepancy between subjective and objective TST within the BDS
group. LIMITATIONS: Subjects are from a tertiary care center and were on
medications for treatment of BD symptoms. CONCLUSION: There is low correlation
between subjective and objective TST in BDS subjects and more severe depressive
symptoms are associated with greater absolute discrepancy in TST. Objective
rather than subjective measures of sleep, such as actigraphy, may be needed to
evaluate sleep in BD subjects. Cognitive-behavioral interventions to address
sleep misperception and associated depressed mood may be indicated in BD.
PMID- 29329057
TI - Chronic corticosterone-induced depression mediates premature aging in rats.
AB - BACKGROUND: Stress hormones such as corticosterone (CORT) play an essential role
in the development of depression. Chronic CORT administration has been shown to
induce dysfunction in the hypothalamic-pituitary-adrenal axis leading to
depression, which was in turn associated with accelerated aging. However, the
effect of CORT administration on aging remains unclear. METHODS: Rats were
acclimatized for 1 week and then injected daily with CORT (40mg/kg) or vehicle (n
= 10 each) for 21 consecutive days. Age-related indexes were then compared
between CORT-treated rats and control rats. RESULTS: CORT induced affective
behaviors indicative of depressive-like symptoms in rats, including reduced
sucrose preference and increased immobility time in the forced swimming test.
CORT-treated rats exhibited telomere shortening, possibly contributing to
decreased telomerase activity and down-regulated expression of telomere-binding
factor 2, correlated with enhanced oxidative damage. This was associated with
inhibition of sirtuin 3 leading to reduced activities of superoxide dismutase 2
and glutathione reductase. CORT-treated rats showed degenerated mitochondrial
functions represented by decreased adenosine triphosphate production, decreased
nicotinamide adenine dinucleotide+ content, and decreased activity of
nicotinamide phosphoribosyltransferase. LIMITATIONS: The group sample sizes were
small, and only male rats and a single dose level of CORT were used. CONCLUSION:
These findings demonstrate that CORT-induced depression may be involved in
mediating the pathophysiology of premature aging in rats.
PMID- 29329058
TI - Association of comorbid personality disorders with clinical characteristics and
outcome in a randomized controlled trial comparing two psychotherapies for early
onset persistent depressive disorder.
AB - BACKGROUND: Persistent depressive disorder (PDD) is associated with high rates of
comorbid personality disorders (PD). The association of comorbid PD and clinical
characteristics has not been systematically studied in PDD. Results regarding
effects on treatment outcome are heterogeneous. METHODS: We analyzed the
association of comorbid personality disorders with clinical characteristics and
outcome in a randomized controlled trial comparing the disorder-specific
Cognitive Behavioral Analysis System of Psychotherapy (CBASP) with nonspecific
supportive psychotherapy (SP) in patients with early-onset PDD. The main outcome
measure was the Hamilton Rating Scale for Depression (HRSD-24). Further baseline
measures were comorbid axis-I diagnoses (SCID-I), quality of life (QLDS), global
functioning (GAF), interpersonal problems (IIP-64) and childhood maltreatment
(CTQ). RESULTS: Out of the 268 patients, 103 (38.4%) met criteria for at least
one PD. PD was associated with higher rates of axis I comorbidities (mainly
anxiety disorders) and interpersonal problems (patients with PD were more
vindictive, more self-sacrificing, less assertive and more inhibited socially
than patients without PD). There was no significant main effect of PD on
treatment outcome and no significant interaction between PD and treatment group.
LIMITATIONS: The main limitation was the exclusion of patients with certain
personality disorders (antisocial, schizotypal, and borderline personality
disorders). Furthermore, the study was underpowered to find interaction effects
of small size. CONCLUSION: Persistently depressed patients with and without
comorbid PD primarily seemed to differ in the rate of axis I comorbidity and the
severity of interpersonal problems. Treatment outcomes appear to be not
significantly affected by the presence of PD.
PMID- 29329059
TI - Amyloid burden and incident depressive symptoms in preclinical Alzheimer's
disease.
AB - BACKGROUND: Relationships between depression and Alzheimer's disease (AD) may
become clearer if studied in preclinical AD where dementia is not present.
METHOD: The aim of this study was to evaluate prospectively, relationships
between brain amyloid-beta (Abeta), depressive symptoms and screen positive
depression in cognitively normal (CN) older adults. Depressive symptoms were
measured with the Geriatric Depression Inventory (GDS-15) in CN adults from the
Australian Imaging Biomarkers and Lifestyle (AIBL) study without depression at
baseline and classified as having abnormally high (Abeta+; n = 136) or low (Abeta
; n = 449) Abeta according to positron emission tomography at 18-month intervals
over 72 months. RESULTS: Incident cases of screen positive depression were not
increased in Abeta+ CN adults although small increases in overall depressive
symptoms severity (d = - 0.25; 95% CI, - 0.45, - 0.05) and apathy-anxiety
symptoms (d = - 0.28; 95% CI - 0.48, - 0.08) were. LIMITATIONS: As the AIBL
sample is an experimental sample, no individuals had severe medical illnesses or
significant psychiatric disorders. Additionally, individuals who had evidence of
screen-positive depression at screening were excluded from enrolment in the AIBL
study. Thus, the current data can be considered only as providing a foundation
for understanding relationships between Abeta and depression in preclinical AD.
CONCLUSIONS: These results suggest that the presence of a depressive disorder or
even increased depressive symptoms are themselves unlikely to be a direct
consequence of increasing Abeta. New depressive disorders presenting in CN older
adults could therefore be investigated for aetiologies beyond AD.
PMID- 29329060
TI - Affective and cognitive reactivity to mood induction in chronic depression.
AB - BACKGROUND: Chronic depression (CD) is strongly associated with childhood
maltreatment, which has been proposed to lead to inefficient coping styles that
are characterized by abnormal affective responsiveness and dysfunctional
cognitive attitudes. However, while this notion forms an important basis for
psychotherapeutic strategies in the treatment of CD, there is still little direct
empirical evidence for a role of altered affective and cognitive reactivity in
CD. The present study therefore experimentally investigated affective and
cognitive reactivity to two forms of negative mood induction in CD patients
versus a healthy control sample (HC). METHODS: For the general mood induction
procedure, a combination of sad pictures and sad music was used, while for
individualized mood induction, negative mood was induced by individualized
scripts with autobiographical content. Both experiments included n = 15 CD
patients versus n = 15 HC, respectively. Interactions between affective or
cognitive reactivity and group were analyzed by repeated measurements ANOVAs.
RESULTS: General mood induction neither revealed affective nor cognitive
reactivity in the patient group while the control group reported the expected
decrease of positive affect [interaction (IA) affective reactivity x group: p =
.011, cognitive reactivity x group: n.s.]. In contrast, individualized mood
induction specifically increased affective reactivity (IA: p = .037) as well as
the amount of dysfunctional cognitions in patients versus controls (IA: p =
.014). LIMITATIONS: The experiments were not balanced in a crossover design,
causal conclusions are thus limited. Additionally, the differences to non-chronic
forms of depression are still outstanding. CONCLUSIONS: The results suggest that
in patients with CD, specific emotional activation through autobiographical
memories is a key factor in dysfunctional coping styles. Psychotherapeutic
interventions aimed at modifying affective and cognitive reactivity are thus of
high relevance in the treatment of CD.
PMID- 29329061
TI - Experimental effects of acute exercise duration and exercise recovery on mood
state.
AB - OBJECTIVE: Accumulating evidence suggests that, in addition to various
psychosocial parameters, affective responses to exercise play an important role
in subserving future exercise behavior. This study comprehensively evaluated
whether acute exercise duration and recovery period influenced the relationship
between moderate-intensity walking exercise and mood profile. METHOD: We employed
a randomized controlled cross-over trial. Participants completed two laboratory
visits, separated by one-week. One of the visits involved a mood profile
assessment with no exercise, while the other visit involved a mood profile
assessment after an acute bout of exercise. Participants (N = 352; 22 per group;
young [Mage = 21 yrs] healthy adults) were randomized into one of 16 experimental
groups: 10, 20, 30, 45 or 60min bout of exercise coupled with either a 5, 15 or
30min recovery period. The exercise bout was of moderate-intensity (40-59% of
HRR). Mood profile was assessed from the POMS survey, considering subscales of
depression, anger and hostility. RESULTS: For all three mood profile parameters,
there was no evidence of a group x time interaction effect. However, the main
effect for time was statistically significant for each mood parameter. These
significant results demonstrate that, generally, exercise had a favorable effect
on each of the mood profile, regardless of exercise duration and recovery period.
In addition to the significant main effects for time, we also observed a
significant main effect for group for the mood parameter hostility. With the
exception of the group 13 (60min of exercise with 5min recovery) and the 3 groups
that employed a 10-min bout of exercise (groups 1-3), all other experimental
groups had a lower (better) hostility score after the exercise visit.
CONCLUSIONS: Generally, exercise had a favorable effect on various mood profiles,
regardless of exercise duration (between 10 and 60min) and recovery period
(between 5 and 30min).
PMID- 29329062
TI - Amygdala response to emotional faces in seasonal affective disorder.
AB - BACKGROUND: Seasonal affective disorder (SAD) is characterized by seasonally
recurring depression. Heightened amygdala activation to aversive stimuli is
associated with major depressive disorder but its relation to SAD is unclear. We
evaluated seasonal variation in amygdala activation in SAD and healthy controls
(HC) using a longitudinal design targeting the asymptomatic/symptomatic phases of
SAD. We hypothesized increased amygdala activation to aversive stimuli in the
winter in SAD individuals (season-by-group interaction). METHODS: Seventeen SAD
individuals and 15 HCs completed an implicit emotional faces BOLD-fMRI paradigm
during summer and winter. We computed amygdala activation (SPM5) to an aversive
contrast (angry & fearful minus neutral) and angry, fearful and neutral faces,
separately. Season-by-group and main effects were evaluated using Generalized
Least Squares. In SAD individuals, we correlated change in symptom severity,
assessed with The Hamilton Rating Scale for Depression - Seasonal Affective
Disorder version (SIGH-SAD), with change in amygdala activation. RESULTS: We
found no season-by-group, season or group effect on our aversive contrast.
Independent of season, SAD individuals showed significantly lower amygdala
activation to all faces compared to healthy controls, with no evidence for a
season-by-group interaction. Seasonal change in amygdala activation was unrelated
to change in SIGH-SAD. LIMITATIONS: Small sample size, lack of positive valence
stimuli. CONCLUSIONS: Amygdala activation to aversive faces is not increased in
symptomatic SAD individuals. Instead, we observed decreased amygdala activation
across faces, independent of season. Our findings suggest that amygdala
activation to angry, fearful and neutral faces is altered in SAD individuals,
independent of the presence of depressive symptoms.
PMID- 29329063
TI - Seasonality of depressive symptoms in women but not in men: A cross-sectional
study in the UK Biobank cohort.
AB - BACKGROUND: We examined whether seasonal variations in depressive symptoms
occurred independently of demographic and lifestyle factors, and were related to
change in day length and/or outdoor temperature. METHODS: In a cross-sectional
analysis of >150,000 participants of the UK Biobank cohort, we used the cosinor
method to assess evidence of seasonality of a total depressive symptoms score and
of low mood, anhedonia, tenseness and tiredness scores in women and men.
Associations of depressive symptoms with day length and mean outdoor temperature
were then examined. RESULTS: Seasonality of total depressive symptom scores,
anhedonia and tiredness scores was observed in women but not men, with peaks in
winter. In women, increased day length was associated with reduced reporting of
low mood and anhedonia, but with increased reporting of tiredness, independent of
demographic and lifestyle factors. Associations with day length were not
independent of the average outdoor temperature preceding assessment. LIMITATIONS:
This was a cross-sectional investigation - longitudinal studies of within-subject
seasonal variation in mood are necessary. Outcome measures relied on self-report
and measured only a subset of depressive symptoms. CONCLUSION: This large,
population-based study provides evidence of seasonal variation in depressive
symptoms in women. Shorter days were associated with increased feelings of low
mood and anhedonia in women. Clinicians should be aware of these population-level
sex differences in seasonal mood variations in order to aid recognition and
treatment of depression and subclinical depressive symptoms.
PMID- 29329064
TI - User acceptability of the diagnosis of prolonged grief disorder: How do
professionals think about inclusion in ICD-11?
AB - BACKGROUND: For the next edition of the International Statistical Classification
of Diseases (ICD-11) it is proposed to include prolonged grief disorder as a new
diagnosis. The diagnosis describes persistent intensive and disabling grief
reactions to bereavement (WHO, 2016b). The aim of the present survey was to
determine the extent to which the diagnosis is accepted by practitioners in the
healthcare and psychosocial field. METHODS: A total of 2088 German-speaking
professionals in the fields of psychotherapy, psychology, counselling, medicine
and palliative care completed the online survey. RESULTS: 42.4% of the
participants felt that the advantages of including the diagnosis outweigh the
disadvantages, 32.9% came to the conclusion that there are more disadvantages.
The remaining 24.7% stated that advantages and disadvantages are balanced. The
proposed classification as separate diagnosis was supported by 24.8%, while 60.0%
preferred alternatives (e.g. as subtype of adjustment disorder). Furthermore, a
time criterion of at least 12 months was voted for considerably more frequently
(49.2%) than the proposed 6 months (11.3%). Objections were predominantly
expressed with regard to pathologization of normal grief and to the difficulty of
adequate crosscultural application of the diagnosis. LIMITATIONS: Results are
limited to predominantly German health-care professionals. The items did not
undergo psychometric analyses. CONCLUSIONS: The disagreement about the diagnosis
found in specialist literature is also reflected in the responses by the
participants. The present results provide stimulation for future questions and
validation studies carried out as part of the ICD revision.
PMID- 29329065
TI - Factors associated with depression among homeless mothers. Results of the ENFAMS
survey.
AB - PURPOSE: Women are disproportionately likely to suffer from depression. This is
especially true for those who experience socioeconomic hardship, such as
homelessness. In France, among homeless mothers many are migrant. However, it is
not clear whether risk factors associated with depression are specific for this
group or the same as in the general population. Our objective was to describe
socio-demographic, relational, living and housing conditions and health factors
associated with depression among homeless mothers. METHODS: The ENFAMS survey,
conducted via face-to-face bilingual interviews with a representative sample of
homeless families in the Paris region (January-May 2013, n = 733 mothers).
Mothers reported their socio-demographic characteristics, housing conditions
including residential mobility, as well as physical and mental health. Depression
was ascertained using the Composite International Diagnostic Interview (CIDI).
Factors associated with mother's depression were studied in weighted Poisson
regression models with robust error variance. RESULTS: The prevalence of
depression among participating mothers was 28.8%. In multivariate analyses,
depression was associated with fluency in French (PR = 1.88 95% CI 1.40; 2.51),
suicide risk (PR = 2.26, 95% CI 1.82; 2.82), post-traumatic stress disorder (PR =
1.97, 95% CI 1.50; 2.60), and unmet health needs (PR = 1.68, 95% CI 1.09; 2.57).
CONCLUSIONS: Homeless mothers have high levels of depression and associated
psychiatric comorbidities. Associated risk factors appear to be both specific for
this group and shared with mothers in the general population. Improvements in the
monitoring of mental health difficulties as well as access to appropriate medical
care in this vulnerable population may help improve health and social outcomes.
PMID- 29329068
TI - "Subcutaneous emphysema" is not always actually in the subcutaneous plane. A Case
of subfascial emphysema after laparoscopy.
PMID- 29329066
TI - Association of suicidal risk with ratings of affective temperaments.
AB - BACKGROUND: Ratings of particular temperament-types with the TEMPS-A
autoquestionnaire have been associated with suicidal risk, and combinations of
such ratings may enhance the association. However, the predictive value of scores
for individual temperaments and combinations remains to be quantified. METHOD: We
evaluated associations of TEMPS-A ratings for anxious (anx), cyclothymic (cyc),
dysthymic (dys), hyperthymic (hyp) and irritable (irr) temperaments, with a
history of suicidal acts or reported suicidal ideation in 882 patients with
bipolar (BD; n = 509), major depressive (MDD; n = 268) or anxiety (ANX; n = 105)
disorders. RESULTS: With BD, scores for cyc and irr were highest and anx lowest;
with MDD, dys scored highest, hyp lowest; anx was highest with ANX and MDD. Women
(n = 497) had higher anx and cyc scores than men; scores for irr and hyp
decreased with age. Scores for dys, anx, and cyc, were higher, and hyp lower,
with greater HDRS21 depression ratings. Among 347 suicidal subjects (112 with
attempts), cyc, dys, and irr scores were higher, hyp lower. Pooled score [cyc+
dys+ irr - hyp] best distinguished subjects with suicide attempts versus
nonsuicidal subjects, including in Receiver-Operating Characteristic (ROC)
analysis (AUC for acts = 70.1% [64.9- 75.3]). Multivariable modeling associated
suicidal acts with TEMPS-A [cyc+ dys+ irr - hyp] composite-score, depression
severity, BD or MDD diagnosis, and older at illness-onset. CONCLUSIONS: Subjects
with suicidal acts or ideation were best distinguished by composite TEMPS-A score
[cyc+ dys+ irr - hyp]. These factors should help to identify those at suicidal
risk.
PMID- 29329069
TI - Supraclavicular brachial plexus block is an alternative to pectoral nerve block 1
for contracture reconstruction post mastectomy.
PMID- 29329067
TI - Case report: Iatrogenic brachial artery dissection with complete anterograde
occlusion during elective arterial line placement.
AB - INTRODUCTION: Brachial arterial catheters provide a more accurate reflection of
central aortic arterial pressure compared to their radial counterparts. Although
brachial arterial line complications are uncommon, we report a case of a rare
iatrogenic brachial artery dissection with complete anterograde occlusion from
elective arterial line placement. PRESENTATION OF CASE: A 41-year-old female
presented for a right upper and middle lobe resection of a large neuroendocrine
lung cancer. A brachial arterial line was inserted for continuous blood pressure
monitoring using clinical landmarks. Six hours postoperatively the left hand was
noted to be pale, cool and pulseless with complete paraesthesia. Thrombus was
initially suspected on computed tomography angiography. Upon return to theatre,
extensive dissection of the posterior brachial arterial wall was identified.
CONCLUSION: We review our diagnostic pathway and treatment of this rare
complication. Recommendations to minimise the risks of complications from
brachial arterial line insertion are also overviewed. We recommend the routine
utilization of ultrasound-guided technique and regular post-insertion
neurovascular monitoring for the prevention and early recognition of
complications from brachial artery catheter insertion.
PMID- 29329070
TI - An alternative technique to use the Trachway(r) for nasotracheal intubation.
PMID- 29329071
TI - Synthesis, anticancer activity and mechanism of action of new thiazole
derivatives.
AB - Thiazole derivatives are recognized to possess various biological activities as
antiparasitic, antifungal, antimicrobial and antiproliferative. The present work
reports the synthesis of 22 new substances belonging to two classes of compounds:
thiosemicarbazones and thiazoles, with the purpose of developing new drugs that
present high specificity for tumor cells and low toxicity to the organism. A
cytotoxic screening was performed to evaluate the performance of the new
derivatives in five tumor cell lines. Eight compounds were shown to be promising
in at least three tumor cell lines. These compounds had their IC50 determined
within 72 h and the activity structure ratio was assessed. The effect of the best
compounds on PBMC and hemolytic activity assay was then evaluated. The compound
1d was considered the most promising among the samples tested and its influence
on cell cycle, DNA fragmentation and mitochondrial depolarization was evaluated.
PMID- 29329072
TI - Development of potent and proteolytically stable human neuromedin U receptor
agonists.
AB - Neuromedin U (NMU) is a highly conserved endogenous peptide that is involved in a
wide range of physiological processes such as regulation of feeding behavior, the
stress response and nociception. The major limitation to use NMU as a therapeutic
is its short half-life. Here, we describe the development of a set of novel NMU
analogs based on NMU-8, by introducing unnatural amino acids into the native
sequence. This approach shows that it is possible to generate molecules with
increased potency and improved plasma stability without major changes of the
peptidic nature or the introduction of large conjugates. When compared to the
native NMU-8 peptide, compounds 16, 18 and 20 have potent agonist activity and
affinity for both NMU receptors. Selectivity towards NMUR1 was observed when the
Phe residue in position 4 was modified, whereas higher potencies at NMUR2 were
found when substitutions of the Pro residue in position 6 were executed. To study
the effect of the modifications on the proteolytic stability of the molecules, an
in vitro stability assay in human plasma at 37 degrees C was performed. All
analyzed analogs possessed an increased resistance against enzymatic degradation
in human plasma resulting in half-lifes from 4 min for NMU-8, up to more than 23
h for compound 42.
PMID- 29329073
TI - Nanobiostructure of fibrous-like alumina functionalized with an analog of the
BP100 peptide: Synthesis, characterization and biological applications.
AB - The functionalization of alumina nanoparticles of specific morphology with
antimicrobial peptides (AMP) can be a promising strategy for modeling medical
devices and packaging materials for cosmetics, medicines or food, since the
contamination by pathogens could be reduced. In this paper, we show the synthesis
of a fibrous-like alumina nanobiostructure, as well as its functionalization with
the peptide EAAA-BP100, an analog of the antimicrobial peptide BP100. The
antibacterial activity of the obtained material against some bacterial strains is
also investigated. The covalent binding of the peptide to the nanoparticles was
promoted by a reaction between the carboxyl group of the glutamate side chain
(E1) of the peptide and the amino groups of the alumina nanoparticles, previously
modified by reaction with 3-aminopropyltrietoxysilane (APTES). The functionalized
nanoparticles were characterized by zeta potential measurements, Fourier
transform infrared spectroscopy, and other physicochemical techniques. Although
the obtained alumina nanobiostructure shows a relatively low degree of
substitution with EAAA-BP100, antibacterial activities against Escherichia coli
and Salmonella typhimurium strains are appreciably higher than the activities of
the free peptide. The obtained results can affect the design of new hybrid
nanobiomaterials based on nanoparticles functionalized with AMP.
PMID- 29329074
TI - Goat tendon collagen-human fibrin hydrogel for comprehensive parametric
evaluation of HUVEC microtissue-based angiogenesis.
AB - The cell and extracellular matrix (ECM) interactions play a very important role
during angiogenesis. Remodeling of the extracellular matrix along with pro
angiogenic/anti-angiogenic factors, and matrix-degrading proteases, accounts for
endothelial cell growth, migration, and tube formation. However, for studying
angiogenesis, only limited and expensive biomaterials are available. Despite
being biocompatible, inexpensive, and easy availability; the potential of goat
tendon collagen (GTC) has never been explored for vascular tissue engineering
applications. Hence, the current investigation was focused on evaluating GTC as
an alternative matrix for HUVEC microtissue-based angiogenesis. HUVEC
microtissues (MTs), synthesized via hanging drop method, were subjected to
angiogenesis in GTC-human fibrin (HF) hydrogels. Sprouting tip cells originated
from the MTs within 24 h. Further, comprehensive in vitro study and in vivo
validation revealed that, endothelial media with FBS and growth factors, 24 h old
HUVEC MTs of 500 cells, seeded at 200 aggregates/cm3 in GTC-HF gel of 100 Pa
elastic modulus, resulted in most optimal angiogenesis with intact lumen that was
stable up to a week, without any supporting cells. Although early to predict, GTC
HF matrix may serve as a potential ECM for engineering complex and functional
tissues of clinical relevance.
PMID- 29329075
TI - Anticoagulant polyurethane substrates modified with poly(2-methacryloyloxyethyl
phosphorylcholine) via SI-RATRP.
AB - A novel catalyst system of Reverse Atom Transfer Radical Polymerization (RATRP)
to prepare Polyurethane (PU) films modified by poly(2-methacryloyloxyethyl
phosphorylcholine) (pMPC) was studied in this article. In this system, PU film
was pretreated by LaCl3/CA ethanol solution to obtain a hydrated surface allowing
more initiators to be immobilized on it. Moreover, complexes composed of silane
coupling agent 3-chloropropyltrimethoxysilane (CPTM), chlorhexidine acetate (CA)
and lanthanum(III) worked as ligands of copper ions as a whole during RATRP
process. PU films before and after modification were characterized by X-ray
photoelectron spectroscopy (XPS) and static contact angle (SCA) to confirm that
pMPC chains were successfully grafted from the substrates. Results of Plasma
recalcification time assay, platelet adhesion test indicated excellent blood
compatibility. Furthermore, the antibacterial activity of the material have been
improved which proved by adhesion test of E.coil.
PMID- 29329077
TI - Nano hydroxyapatite-blasted titanium surface creates a biointerface able to
govern Src-dependent osteoblast metabolism as prerequisite to ECM remodeling.
AB - Over the last several years, we have focused on the importance of intracellular
signaling pathways in dynamically governing the biointerface between pre
osteoblast and surface of biomaterial. Thus, this study investigates the
molecular hallmarks involved in the pre-osteoblast relationship with different
topography considering Machined (Mc), Dual Acid-Etching (DAE), and nano
hydroxyapatite-blasted (nHA) groups. There was substantial differences in
topography of titanium surface, considering Atomic Force Microscopy and water
contact angle (Mc = 81.41 +/- 0.01; DAE = 97.18 +/- 0.01; nHA = 40.95 +/- 0.02).
Later, to investigate their topography differences on biological responses, pre
osteoblast was seeded on the different surfaces and biological samples were
collected after 24 h (to consider adhesion signaling) and 10 days (to consider
differentiation signaling). Preliminary results evidenced significant differences
in morphological changes of pre-osteoblasts mainly resulting from the interaction
with the DAE and nHA, distinguishing cellular adaptation. These results pushed us
to analyze activation of specific genes by exploring qPCR technology. In
sequence, we showed that Src performs crucial roles during cell adhesion and
later differentiation of the pre-osteoblast in relationship with titanium-based
biomaterials, as our results confirmed strong feedback of the Src activity on the
integrin-based pathway, because integrin-beta1 (~5-fold changes), FAK (~12-fold
changes), and Src (~3.5-fold changes) were significantly up-expressed when Src
was chemically inhibited by PP1 (5 MUM). Moreover, ECM-related genes were
rigorously reprogrammed in response to the different surfaces, resulting on
Matrix Metalloproteinase (MMP) activities concomitant to a significant decrease
of MMP inhibitors. In parallel, we showed PP1-based Src inhibition promotes a
significant increase of MMP activity. Taking all our results into account, we
showed for the first time nano hydroxyapatite-blasted titanium surface creates a
biointerface able to govern Src-dependent osteoblast metabolism as pre-requisite
to ECM remodeling.
PMID- 29329076
TI - Attachment of nanoparticulate drug-release systems on poly(epsilon-caprolactone)
nanofibers via a graftpolymer as interlayer.
AB - Electrospun poly(epsilon-caprolactone) (PCL) fiber mats are modified using a
chitosan grafted with PCL (CS-g-PCL), to improve the biological performance and
to enable further modifications. The graft copolymer is immobilized by the
crystallization of the PCL grafts on the PCL fiber surface as binding mechanism.
In this way, the surface of the fibers is covered with chitosan bearing cationic
amino groups, which allow adsorption of oppositely charged nanoparticulate drug
delivery systems. The modification of the fiber mats and the attachment of the
drug delivery systems are easy and scalable dip processes. The process is also
versatile; it is possible to attach different polymeric and inorganic
nanoparticulate drug-release systems of cationic or anionic nature. The
modifications are verified using scanning electron microscopy (SEM) and confocal
laser scanning microscopy (CLSM). As proof of principle, the release of
ciprofloxacin from silica nanoparticles attached to the modified fiber mats is
shown; however, the method is also suited for other biologically active
substances including growth factors. The initial cellular attachment and
proliferation as well as vitality of the cells is improved by the modification
with CS-g-PCL and is further influenced by the type of the drug delivery system
attached. Hence, this method can be used to transfer PCL fiber mats into
bioactive implants for in-situ tissue engineering applications.
PMID- 29329078
TI - Schmallenberg virus non-structural protein NSm: Intracellular distribution and
role of non-hydrophobic domains.
AB - Schmallenberg virus (SBV) induces fetal malformation, abortions and stillbirth in
ruminants. While the non-structural protein NSs is a major virulence factor, the
biological function of NSm, the second non-structural protein which consists of
three hydrophobic transmembrane (I, III, V) and two non-hydrophobic regions (II,
IV), is still unknown. Here, a series of NSm mutants displaying deletions of
nearly the entire NSm or of the non-hydrophobic domains was generated and the
intracellular distribution of NSm was assessed. SBV-NSm is dispensable for the
generation of infectious virus and mutants lacking domains II - V showed growth
properties similar to the wild-type virus. In addition, a comparable
intracellular distribution of SBV-NSm was observed in mammalian cells infected
with domain II mutants or wild-type virus. In both cases, NSm co-localized with
the glycoprotein Gc in the Golgi compartment. However, domain IV-deletion mutants
showed an altered distribution pattern and no co-localization of NSm and Gc.
PMID- 29329080
TI - Intrauterine inflammatory activation, functional progesterone withdrawal, and the
timing of term and preterm birth.
AB - The central role of inflammatory processes in labour and delivery is now well
recognised. However, the biomolecular, immunological and endocrine mechanisms
involved in the labour process, and the clinical manifestations of inflammation
in pregnancy, are complex, variable and modulated by factors such as aetiology,
ethnicity and gestational age. In this review, evidence is presented of the
pivotal relationship between progesterone and inflammation in pregnancy in terms
of determining the timing of labour and delivery. The maternal inflammatory
burden increases with advancing gestational age in response to endocrine,
maturational, physical, metabolic and biochemical drivers, leading to functional
progesterone withdrawal necessary for labour and delivery. Variability in the
nature, timing and magnitude of these drivers influence the timing of delivery
and the likelihood of preterm birth. Pathological inflammatory insults in
pregnancy, such as infection, oxidative stress, senescence and maternal allograft
rejection, can precipitate preterm birth, often involving common signalling
pathways. Intrauterine infection is an important cause of early preterm birth,
associated with delivery of the infants at greatest risk of death and disability;
however, most preterm deliveries with intrauterine inflammatory activation are
not infection-associated. This observation has important diagnostic and
therapeutic implications and challenges. The key differences and similarities
between infection-associated and sterile inflammation in this context are
highlighted, and the clinical implications and significance of these processes
and how they might be exploited are discussed.
PMID- 29329081
TI - Presence of Fe-Al binary oxide adsorbent cake layer in ceramic membrane
filtration and their impact for removal of HA and BSA.
AB - To enhance the removal of natural organic matter (NOM) in ceramic (Ce) membrane
filtration, an iron-aluminum binary oxide (FAO) was applied to the ceramic
membrane surface as the adsorbent cake layer, and it was compared with heated
aluminum oxide (HAO) for the evaluation of the control of NOM. Both the HAO and
FAO adsorbent cake layers efficiently removed the NOM regardless of NOM's
hydrophobic/hydrophilic characteristics, and the dissolved organic carbon (DOC)
removal in NOM for FAO was 1-1.12 times greater than that for HAO, which means
FAO was more efficient in the removal of DOC in NOM. FAO (0.03 MUm), which is
smaller in size than HAO (0.4 MUm), had greater flux reduction than HAO. The flux
reduction increased as the filtration proceeded because most of the organic
foulants (colloid/particles and soluble NOM) were captured by the adsorbent cake
layer, which caused fouling between the membrane surface and the adsorbent cake
layer. However, no chemically irreversible fouling was observed on the Ce
membrane at the end of the FAO adsorbent cake layer filtration. This means that a
stable adsorbent cake layer by FAO formed on the Ce membrane, and that the
reduced pure water flux of the Ce membrane, resulting from the NOM fouling, can
easily be recovered through physicochemical cleaning.
PMID- 29329079
TI - The interactome of EBV LMP1 evaluated by proximity-based BioID approach.
AB - Epstein-Barr virus LMP1 is an oncoprotein required for immortalizing B
lymphocytes and also plays important roles in transforming non-lymphoid tissue.
The discovery of LMP1 protein interactions will likely generate targets to treat
EBV-associated cancers. Here, we define the broader LMP1 interactome using the
recently developed BioID method. Combined with mass spectrometry, we identified
over 1000 proteins across seven independent experiments with direct or indirect
relationships to LMP1. Pathway analysis suggests that a significant number of the
proteins identified are involved in signal transduction and protein or vesicle
trafficking. Interestingly, a large number of proteins thought to be important in
the formation of exosomes and protein targeting were recognized as probable LMP1
interacting partners, including CD63, syntenin-1, ALIX, TSG101, HRS, CHMPs, and
sorting nexins. Therefore, it is likely that LMP1 modifies protein trafficking
and exosome biogenesis pathways. In support of this, knock-down of syntenin-1 and
ALIX resulted in reduced exosomal LMP1.
PMID- 29329082
TI - The domestic fowl (Gallus gallus domesticus) embryo as an alternative for
mammalian experiments - Validation of a test method for the detection of
endocrine disrupting chemicals.
AB - In recent decades the embryo of Gallus g. domesticus has been widely used as a
model for the study of early sexual development and the potential impact of
substances affecting development, including endocrine disrupting chemicals
(EDCs). Since there is no standardized procedure available for experiments with
the chicken embryo, the objective of our project is to expedite the protocol to
assess the potential effects of EDCs on early sexual differentiation. The main
aim of the present study was to systematically investigate the natural
variability of individual developmental and histological key parameters in
untreated and solvent-treated control groups, since this has been insufficiently
addressed so far. A further aim was to provide robust values for all parameters
investigated in control and substance experiments, using two known estrogenic
compounds, bisphenol A (75/150/300 MUg/g egg) and 17alpha-ethinylestradiol (20
ng/g egg). On embryonic day 1 eggs were injected with the estrogenic compounds.
On embryonic day 19 histological gonadal data as well as morphological parameters
were noted. In baseline experiments with control groups the selected endpoints
showed reproducible results with low variabilities. Furthermore, gonadal
endpoints responded sensitively to the treatment with the two model EDCs. Thus,
these endpoints are recommended for the assessment of suspected EDCs in which the
values provided for all parameters can serve as validity criteria in future
experiments. The embryo of G. domesticus has shown to be a suitable alternative
to currently accepted mammalian bioassays for the impact assessment of EDCs on
reproductive tissues.
PMID- 29329083
TI - A label-free electrochemical system for comprehensive monitoring of o
chlorophenol.
AB - o-Chlorophenol (OCP) is a priority pollutant that poses serious health threats to
the public. The following study designs a simple electrochemical system to
monitor the concentration and toxicity of OCP. This system was primarily
characterized by the integration of both physicochemical and biological
monitoring procedures that had a synergistic effect between the functionalized
carbon nanotubes and rhodamine B. This resulted in excellent electrocatalytic
activities toward OCP and cellular purine bases. The peak current of OCP was
linear with concentrations ranging from 0.05-125.0 MUM and the detection limit
was 0.028 MUM under optimal testing conditions. There was an enhanced
voltammetric signal detected that was caused by the guanine/xanthine of human
hepatoma (HepG2) cells. The cytotoxicity of OCP to HepG2 cells was assessed using
the proposed system. The obtained IC50 value was 512.86 MUM. This study provided
a fast, label-free, and low-cost platform for the comprehensive assessment of
OCP. This is highly beneficial for simplifying the environmental monitoring
process.
PMID- 29329085
TI - An integrated approach to assess the impacts of zinc pyrithione at different
levels of biological organization in marine mussels.
AB - The mechanisms of sublethal toxicity of the antifouling biocide, zinc pyrithione
(ZnPT), have not been well-studied. This investigation demonstrates that 14-d
sublethal exposure to ZnPT (0.2 or 2 MUM, alongside inorganic Zn and sea water
controls) is genotoxic to mussel haemocytes but suggests that this is not caused
by oxidative DNA damage as no significant induction of oxidised purines was
detected by Fpg-modified comet assay. More ecologically relevant endpoints,
including decreased clearance rate (CR), cessation of attachment and decreased
tolerance of stress on stress (SoS), also showed significant response to ZnPT
exposure. Our integrated approach was underpinned by molecular analyses (qRT-PCR
of stress-related genes, 2D gel electrophoresis of proteins) that indicated ZnPT
causes a decrease in phosphoenolpyruvate carboxykinase (PEPCK) expression in
mussel digestive glands, and that metallothionein genes are upregulated; PEPCK
downregulation suggests that altered energy metabolism may also be related to the
effects of ZnPT. Significant relationships were found between % tail DNA (comet
assay) and all higher level responses (CR, attachment, SoS) in addition to PEPCK
expression. Principal component analyses suggested that expression of selected
genes described more variability within groups whereas % tail DNA reflected
different ZnPT concentrations.
PMID- 29329084
TI - Sources of polychlorinated dibenzo-p-dioxins and dibenzofurans, and biphenyls in
Chinese mitten crabs.
AB - Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated
biphenyls (PCBs) in Chinese mitten crabs from several areas were determined. The
toxic equivalents (TEQs) for the mean PCDD/F and total PCDD/F and dioxin-like
PCBs were 2.9 +/- 2.7 and 5.7 +/- 4.0 pg TEQ g-1, respectively. The mean
concentrations of PCBs and dl-PCBs were 282 and 59 times the concentrations of
PCDD/Fs, respectively. PCDD/F and PCB sources in the crab food web were assessed.
The total TEQ of PCDD/F and PCB supplied by crab compound feed was 2.1 times the
TEQ in crab meat. Broken corn, aquatic biota, and water contributed around 12% of
the total TEQ inputs for crab meat. The contribution from sediment was around 164
times that from crab meat, and sediment may be the most important source of
PCDD/Fs and PCBs in cultured crabs. Principal component analysis (PCA) and stable
isotope ratios for nitrogen (delta15N) and carbon (delta13C) supported the TEQ
results. The mean total PCDD/F and dl-PCB TEQ exposure for humans consuming crabs
was 3.4 pg TEQ per kilogram of body weight per day. The PCDD/Fs and PCBs in >80%
of the crab samples would not cause the tolerable daily intake to be exceeded.
PMID- 29329086
TI - Effect of exogenous phosphate on the lability and phytoavailability of arsenic in
soils.
AB - The effect of exogenous phosphate (P, 200 mg?kg-1 soil) on the lability and
phytoavailability of arsenic (As) was studied using the diffusive gradients in
thin films (DGT) technique. Lettuce were grown on the As-amended soils following
the stabilization of soil labile As after 90 days incubation. Phosphate (P)
application generally facilitated plant growth except one grown on P-sufficient
soil. Soil labile As concentration increased in all the soils after P application
due to a competition effect. Plant As concentration increased in red soils
collected from Hunan Province, while decreases were observed in the other soils.
Even though, an overall trend of decrease was obtained in As phytoavailability
along with the increase of DGT-measured soil labile P/As molar ratio. The
functional equation between P/As and As phytoavailability provided a critical
value of 1.7, which could be used as a guidance for rational P fertilization,
thus avoiding overfertilization.
PMID- 29329087
TI - Occurrence of perfluoroalkyl substances (PFAS) in garden produce at homes with a
history of PFAS-contaminated drinking water.
AB - The decades-long disposal of manufacturing waste containing perfluoroalkyl
substances (PFAS) in landfills resulted in contamination of groundwater serving
as the drinking water supply for the eastern Twin Cities metropolitan region.
While measures were taken to reduce the levels of PFAS in the drinking water,
questions remained about possible non-drinking water pathways of exposure in
these communities. The Minnesota Department of Health (MDH) investigated whether
PFAS in water used for yard and garden irrigation results in elevated
concentrations of PFAS in soil and home-grown produce. In 2010, samples of
outdoor tap water, garden soil, and garden produce were collected at homes
impacted by the contamination and analyzed for several PFAS. Perfluorobutanoic
acid (PFBA) was the primary PFAS present in water, followed by perfluoropentanoic
acid (PFPeA). Although PFBA, perfluorooctanoic acid (PFOA) and perfluorooctane
sulfonate (PFOS) were present in 100% of soil samples at higher concentrations
compared to other PFAS, only PFBA was readily translocated to plants. Significant
determinants of PFBA concentration in produce were the amount of PFBA applied to
the garden via watering and the type of produce tested. Results from this real
world study are consistent with experimental findings that short-chain PFAS have
the highest potential to translocate to and bioaccumulate in edible plants. These
findings are globally relevant, as short-chain PFAS serve as commercial
substitutes for longer-chain compounds and are increasingly detected in water due
to their relatively high solubility and mobility.
PMID- 29329088
TI - Metal sorption to Spodosol Bs horizons: Organic matter complexes predominate.
AB - While metal sorption mechanisms have been studied extensively for soil surface
horizons, little information exists for subsoils, for example Spodosol Bs
horizons. Here the sorption of cadmium(II), copper(II) and lead(II) to seven Bs
horizons from five sites was studied. Extended X-ray absorption fine structure
(EXAFS) spectroscopy showed that cadmium(II) and lead(II) were bound as inner
sphere complexes to organic matter. Addition of o-phosphate (to 1 MUmol l-1) did
not result in any significant enhancement of metal sorption, nor did it influence
EXAFS speciation. An assemblage model using the SHM and CD-MUSIC models
overestimated metal sorption for six out of seven soil samples. To agree with
experimental results, substantial decreases (up to 8-fold) had to be made for the
fraction 'active organic matter', fHS, while the point-of-zero charge (PZC) of
ferrihydrite had to be increased. The largest decreases of fHS were found for the
soils with the lowest ratio of pyrophosphate-to oxalate-extractable Al
(Alpyp/Alox), suggesting that in these soils, humic and fulvic acids were to a
large extent inaccessible for metal sorption. The low reactivity of ferrihydrite
towards lead(II) can be explained by potential spillover effects from co-existing
allophane, but other factors such as ferrihydrite crystallisation could not be
ruled out. In conclusion, organic matter was the predominant sorbent for
cadmium(II), copper(II) and lead(II). However, for lead(II) the optimised model
suggests additional, but minor, contributions from Fe (hydr)oxide surface
complexes. These results will be important to correctly model metal sorption in
spodic materials.
PMID- 29329089
TI - Neural circuit dysfunction in mouse models of neurodevelopmental disorders.
AB - Neuropsychiatric disorders arise from the alteration of normal brain
developmental trajectories disrupting the function of specific neuronal circuits.
Recent advances in human genetics have greatly accelerated the identification of
genes whose variation increases the susceptibility for neurodevelopmental
disorders, most notably for autism spectrum disorder (ASD) and schizophrenia. In
parallel, experimental studies in animal models-most typically in mice-are
beginning to shed light on the role of these genes in the development and
function of specific brain circuits. In spite of their limitations, understanding
the impact of pathological gene variation in animal models at the level of
specific neuronal populations and circuits will likely contribute to orienting
human clinical studies in the search for precise disease mechanisms and novel
treatments.
PMID- 29329090
TI - Simultaneous accelerated solvent extraction and hydrolysis of 11-nor-Delta9
tetrahydrocannabinol-9-carboxylic acid glucuronide in meconium samples for gas
chromatography-mass spectrometry analysis.
AB - Cannabis misuse during pregnancy is associated with severe impacts on the mother
and baby health, such as newborn low birth weight, growth restriction, pre-term
birth, neurobehavioral and developmental deficits. In most of the cases, drug
abuse is omitted or denied by the mothers. Thus, toxicological analyzes using
maternal-fetal matrices takes place as a suitable tool to assess drug use.
Herein, meconium was the chosen matrix to evaluate cannabis exposure through
identification and quantification of 11-nor-Delta9-tetrahydrocannabinol-9
carboxylic (THCCOOH). Accelerated solvent extraction (ASE) was applied for sample
preparation technique to simultaneously extract and hydrolyze conjugated THCCOOH
from meconium, followed by a solid-phase extraction (SPE) procedure. The method
was developed and validated for gas chromatography-mass spectrometry (GC-MS),
reaching hydrolysis efficiency of 98%. Limits of detection (LOD) and
quantification (LOQ) were, respectively, 5 and 10 ng/g. The range of linearity
was LOQ to 500 ng/g. Inter and intra-batch coefficients of variation were <8.4%
for all concentration levels. Accuracy was in 101.7-108.9% range. Recovery was on
average 60.3%. Carryover effect was not observed. The procedure was applied in
six meconium samples from babies whose mothers were drug users and showed
satisfactory performance to confirm fetal cannabis exposure.
PMID- 29329091
TI - Determination of IMM-H004 and its active glucuronide metabolite in rat plasma and
Ringer's solution by ultra-performance liquid chromatography-tandem mass
spectrometry.
AB - IMM-H004 is a novel neuroprotective agent and its glucuronide metabolite IMM
H004G has similar protective effects against cerebral ischemic injury in vivo and
in vitro. A specific and sensitive ultra-performance liquid chromatography-tandem
mass spectrometry method was established and validated for determination of IMM
H004 and IMM-H004G simultaneously in rat plasma and Ringer's solution. Plasma
samples containing IMM-H004, IMM-H004G and internal standard propranolol were
prepared by direct protein precipitation in a sample-to-solvent ratio of 1:2:6
(plasma: water: acetonitrile), whereas no protein precipitation was required for
Ringer's solution samples. Separation was performed with a gradient mobile phase
of methanol/water with 0.5% formic acid (v/v) on Eclipse Plus C18 column
(2.1*50mm, 3.5MUm) at a flow rate of 0.3mL/min. The detection was operated on a
triple quadrupole mass spectrometer in positive ion multiple reaction monitoring
(MRM) mode. The monitored transitions were 305.1->248.1 for IMM-H004, 481.3
>305.1 for IMM-H004G and 260.1->183.1 for propranolol. The linear ranges of IMM
H004 and IMM-H004G were 5 to 3000ng/mL and 10 to 3000ng/mL for plasma method and
0.5 to 500ng/mL for Ringer's solution method. All the intra-day and inter-day
precision and accuracy for the two analytes in rat plasma were below 7.5% and the
intra-day precision and accuracy for analytes in Ringer's solution were within +/
14.7%. There was no obvious matrix effect and the recoveries of the analytes were
higher than 94.2%. IMM-H004 and IMM-H004G were stable during one analytic
process. The established method was applied successfully to plasma
pharmacokinetic and brain microdialysis studies of IMM-H004 and IMM-H004G in rats
after a single intravenous administration of IMM-H004.
PMID- 29329092
TI - Effect of aspirin on the pharmacokinetics and absorption of panax notoginseng
saponins.
AB - BACKGROUND: Panax notoginseng saponins, a traditional Chinese medicine
extraction, and aspirin are both widely used to treat cerebral infarction in
China. Good results in clinical practice have been achieved, when Panax
notoginseng saponins was taken together with aspirin. METHODS: To investigate the
interaction of the two drugs in vivo, the concentration of notoginsenoside R1,
ginsenoside Rg1, Rb1, Re and Rd. in blood were simultaneously measured by
UPLC/MS/MS. Sample preparation was carried out by the protein precipitation
technique with an internal standard saikosaponin A standard. The separation of
six components was achieved by using an ACQUITY UPLC (r)BEH C18 column (1.7MUm
2.1*100mm) by gradient elution using water (containing 0.2% formic acid) and
acetonitrile (containing 0.2% formic acid) as the mobile phase at a flow rate of
0.2mL/min. The pharmacokinetic parameters were determined using non-compartmental
analysis. The transport of notoginsenoside R1, ginsenoside Rg1, Rb1, Re and Rd.
in MDCK -MDR1 cell monolayer was also used to verify the conclusion of
pharmacokinetic drug-drug interaction and study the mechanism of drug
interaction. RESULTS: The concentrations of the five components increased in a
certain extent when the two drugs administered together in rats. The values of
apparent permeability coefficients were significantly increased when the two
drugs were used together. Aspirin and salicylic acid could destroy the tight
junction protein and open the intercellular space to increase the absorption of
Panax notoginseng saponins. CONCLUSION: Pharmacokinetic drug-drug interaction in
vivo existed between Panax notoginseng saponins and aspirin. The drug-drug
interaction mainly occurred in the process of absorption.
PMID- 29329093
TI - Size exclusion chromatography (SEC-HPLC) as an alternative to study thrombin
inhibition.
AB - In vitro analysis of anticoagulant compounds with a potential use as
antithrombotic drugs, has been traditionally performed using techniques like
spectrophotometry, turbidimetry, as well as electrochemical and clinical assays.
Although, these techniques have some disadvantages such as: the inability to
measure the total biological activity of thrombin, interferences and, sometimes,
the quantitative determination of the inhibition ratio is not accurate. In the
present work, the conversion of fibrinogen to fibrin was monitored by molecular
exclusion chromatography (SEC-HPLC) in three different reaction systems. An
inhibition percentage of 43.19+/-2.02% was obtained using heparin as an
anticoagulant, in addition to the determination of the percentage of heparin
bonded to thrombin. This methodology has not been previously described and has
high potential for the determination of anticoagulant capacity with higher
precision, the determination of thrombin's total biological activity and the
quantitative determination of the inhibition ratio.
PMID- 29329094
TI - Hydrophilic interaction liquid chromatography in the speciation analysis of
selenium.
AB - The hydrophilic interaction liquid chromatography (HILIC) coupled to mass
spectrometry was employed to study retention behavior of selected selenium
compounds using two different HILIC stationary phases: silica and zwitterionic.
Two organic solvents - acetonitrile and methanol - were compared as a component
of mobile phase. Separation parameters such as a content of organic modifier, the
eluent pH and inorganic buffer concentration were investigated. Based on all
observations, methanol seems to be beneficial for the separation of studied
compounds. The optimal HILIC separation method involved silica column and eluent
composed of 85% MeOH and CH3COONH4 (8 mM, pH 7) was compared to RP method in
terms of time of the single run, the separation efficiency and limit of
detection.
PMID- 29329095
TI - Investigation of silver (Ag) deposition in tissues from stranded cetaceans by
autometallography (AMG).
AB - Silver, such as silver nanoparticles (AgNPs), has been widely used in commercial
products and may be released into the environment. The interaction between Ag
deposition and biological systems is raising serious concerns because of one
health consideration. Cetaceans, as the top predators of the oceans, may be
exposed to Ag/Ag compounds and suffer negative health impacts from the deposition
of these compounds in their bodies. In the present study, we utilized
autometallography (AMG) to localize the Ag in the liver and kidney tissues of
cetaceans and developed a model called the cetacean histological Ag assay (CHAA)
to estimate the Ag concentrations in the liver and kidney tissues of cetaceans.
Our results revealed that Ag was mainly located in hepatocytes, Kupffer cells and
the epithelial cells of some proximal renal tubules. The tissue pattern of Ag/Ag
compounds deposition in cetaceans was different from those in previous studies
conducted on laboratory rats. This difference may suggest that cetaceans have a
different metabolic profile of Ag, so a presumptive metabolic pathway of Ag in
cetaceans is advanced. Furthermore, our results suggest that the Ag contamination
in cetaceans living in the North-western Pacific Ocean is more severe than that
in cetaceans living in other marine regions of the world. The level of Ag
deposition in cetaceans living in the former area may have caused negative
impacts on their health condition. Further investigations are warranted to study
the systemic Ag distribution, the cause of death/stranding, and the infectious
diseases in stranded cetaceans with different Ag concentrations for
comprehensively evaluating the negative health effects caused by Ag in cetaceans.
PMID- 29329096
TI - Water contamination by endocrine disruptors: Impacts, microbiological aspects and
trends for environmental protection.
AB - Hormone active agents constitute a dangerous class of pollutants. Among them,
those agents that mimic the action of estrogens on target cells and are part of
the group of endocrine-disruptor compounds (EDCs) are termed estrogenic EDCs, the
main focus of this review. Exposure to these compounds causes a number of
negative effects, including breast cancer, infertility and animal
hermaphroditism. However, especially in underdeveloped countries, limited efforts
have been made to warn people about this serious issue, explain the methods of
minimizing exposure, and develop feasible and efficient mitigation strategies at
different levels and in various environments. For instance, the use of
bioremediation processes capable of transforming EDCs into environmentally
friendly compounds has been little explored. A wide diversity of estrogen
degrading microorganisms could be used to develop such technologies, which
include bioremediation processes for EDCs that could be implemented in biological
filters for the post-treatment of wastewater effluent. This review describes
problems associated with EDCs, primarily estrogenic EDCs, including exposure as
well as the present status of understanding and the effects of natural and
synthetic hormones and estrogenic EDCs on living organisms. We also describe
potential biotechnological strategies for EDC biodegradation, and suggest novel
treatment approaches for minimizing the persistence of EDCs in the environment.
PMID- 29329097
TI - Sources and transformation pathways for dichlorodiphenyltrichloroethane (DDT) and
metabolites in soils from Northwest Fujian, China.
AB - Dicofol (2,2,2-trichloro-1,1-bis-(p-chlorophenyl)ethanol) found in the
environment is not only a miticide originated from commercial use, but also a
metabolite of dichlorodiphenyltrichloroethane (DDT), which is often overlooked.
To verify the sources and transformation pathways of DDT and related metabolites
in soils, we measured p,p'-(dicofol + DBP) (sum of p,p'-dicofol and 4,4'
dichlorobenzophenone), DDT and six metabolites in soils from Northwest Fujian,
China. The ratios of 1,1,1-trichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane
(o,p'-DDT)/1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane (p,p'-DDT) and the mass
balance demonstrated that p,p'-(dicofol + DBP) predominantly originated from p,p'
DDT transformation rather than from actual dicofol application. p,p'-(dicofol +
DBP) accounted for 45.0% as the primary metabolites of DDT in this study, more
than 1,1-dichloro-2,2-bis-(p-chlorophenyl)ethylene (p,p'-DDE) and 1,1-dichloro
2,2-bis-(p-chlorophenyl)ethane (p,p'-DDD), which might lead to large
overestimations of the fresh DDT input by using the traditional ratio of (?2DDD +
?2DDE)/?2DDT (with all o,p'- and p,p'- isomers included). In paddy fields where
the conditions alternate between aerobic (dry period) and anaerobic (wet period),
both p,p'-DDD and p,p'-DDE were likely to degrade to 1-chloro-2,2-bis-(p
chlorophenyl)ethylene (p,p'-DDMU), which further transformed to 2,2-bis(p
chlorophenyl)ethylene (p,p'-DDNU). Degradation of p,p'-DDMU to p,p'-DDNU mainly
occurred in waterlogged paddy soils. However, p,p'-DDNU might not transform to
other higher-order metabolites in aerobic surface soils. Overall, our study
confirmed p,p'-(dicofol + DBP) as metabolites of p,p'-DDT, suggested DDE and DDD
were parallel precursors of DDMU, and further verified the transformation
pathways of DDT in surface soils.
PMID- 29329098
TI - Effect of organic amendments on cadmium stress to pea: A multivariate comparison
of germinating vs young seedlings and younger vs older leaves.
AB - Despite significant recent advancement in research, biogeochemical behavior of
heavy metals with respect to their applied form is still topical. Moreover, metal
toxicity to plants may vary with their stage of development/maturity. Therefore,
this study for the first time evaluated the influence of
ethylenediaminetetraacetic acid (EDTA) and citric acid (CA) on cadmium (Cd)
accumulation and toxicity to germinating and young pea seedlings as well as in
younger and older leaves. The experimental setup of current study consisted of
two separate studies. The first study was performed on germinating seedlings
grown in a Cd-contaminated sand media. Pea seeds were treated with two levels of
Cd (Cd-25 and Cd-100) alone and combined with different levels of EDTA and CA.
The second study was carried out in hydroponic solution. The influence of organic
amendments on Cd accumulation and toxicity to pea plants was evaluated by
determining Cd contents in pea seedlings, H2O2 contents, chlorophyll contents and
lipid peroxidation in younger and older leaves. Cadmium stress caused
overproduction of H2O2 in roots and leaves of pea seedlings. Cadmium-induced
overproduction of H2O2 caused a decrease in the pigment contents and increased
lipid peroxidation. Application of EDTA at higher levels (81 and 200uM) increased
Cd accumulation by pea plants. However, CA did not affect Cd accumulation by pea.
Both EDTA and CA increased Cd-induced H2O2 production and lipid peroxidation.
Younger pea leaves showed more sensitivity to Cd stress compared to older leaves.
Similarly, Cd toxicity was more pronounced in germinating seedlings than young
seedlings. Moreover, Pearson correlation and principal component analysis (PCA)
showed very interesting correlations between treatments and stress responses of
germination and young seedlings as well as younger and older leaves. Based on
multivariate analysis, it is proposed that the Cd toxicity to pea plants greatly
vary with its growth stage and the maturity of organs (younger or older leaves).
PMID- 29329099
TI - Accumulation patterns and risk assessment of metals and metalloid in muscle and
offal of free-range chickens, cattle and goat in Benin City, Nigeria.
AB - The use of free range animals for monitoring environmental health offers
opportunities to detect exposure and assess the toxicological effects of
pollutants in terrestrial ecosystems. Potential human health risk of dietary
intake of metals and metalloid via consumption of offal and muscle of free range
chicken, cattle and goats by the urban population in Benin City was evaluated.
Muscle, gizzard, liver and kidney samples were analyzed for Cr, Mn, Fe, Co, Ni,
Cu, Zn, As, Cd, and Pb concentrations using inductively coupled plasma mass
spectrometer (ICP-MS) while Hg was determined using Hg analyzer. Mean
concentrations of metals (mg/kg ww) varied significantly depending upon the
tissues and animal species. Human health risk estimations for children and adults
showed estimated daily intake (EDI) values of tissues below oral reference dose
(RfD) threshold for non essential metals Cd, As, Pb and Hg thus strongly
indicating no possible health risk via consumption of animal based food.
Calculated Hazard quotient (THQ) was less than 1 (< 1) for all the metals
analyzed for both adult and children. However, Cd and As had the highest value of
THQ suggestive of possible health risk associated with continuous consumption of
Cd and As contaminated animal based foods. Hazard Index (HI) for additive effect
of metals was higher in chicken liver and gizzard for children and chicken liver
for adults. Thus, HI indicated that chicken liver and gizzard may contribute
significantly to adult and children dietary exposure to heavy metals. Principal
component analysis (PCA) showed a clear species difference in metal accumulation
between chickens and the ruminants. This study provides baseline data for future
studies and also valuable evidence of anthropogenic impacts necessary to initiate
national and international policies for control of heavy metal and metalloid
content in food items.
PMID- 29329100
TI - A Web-Based System for Bayesian Benchmark Dose Estimation.
AB - BACKGROUND: Benchmark dose (BMD) modeling is an important step in human health
risk assessment and is used as the default approach to identify the point of
departure for risk assessment. A probabilistic framework for dose-response
assessment has been proposed and advocated by various institutions and
organizations; therefore, a reliable tool is needed to provide distributional
estimates for BMD and other important quantities in dose-response assessment.
OBJECTIVES: We developed an online system for Bayesian BMD (BBMD) estimation and
compared results from this software with U.S. Environmental Protection Agency's
(EPA's) Benchmark Dose Software (BMDS). METHODS: The system is built on a
Bayesian framework featuring the application of Markov chain Monte Carlo (MCMC)
sampling for model parameter estimation and BMD calculation, which makes the BBMD
system fundamentally different from the currently prevailing BMD software
packages. In addition to estimating the traditional BMDs for dichotomous and
continuous data, the developed system is also capable of computing model-averaged
BMD estimates. RESULTS: A total of 518 dichotomous and 108 continuous data sets
extracted from the U.S. EPA's Integrated Risk Information System (IRIS) database
(and similar databases) were used as testing data to compare the estimates from
the BBMD and BMDS programs. The results suggest that the BBMD system may
outperform the BMDS program in a number of aspects, including fewer failed BMD
and BMDL calculations and estimates. CONCLUSIONS: The BBMD system is a useful
alternative tool for estimating BMD with additional functionalities for BMD
analysis based on most recent research. Most importantly, the BBMD has the
potential to incorporate prior information to make dose-response modeling more
reliable and can provide distributional estimates for important quantities in
dose-response assessment, which greatly facilitates the current trend for
probabilistic risk assessment. https://doi.org/10.1289/EHP1289.
PMID- 29329101
TI - Spatial Variation of Endotoxin Concentrations Measured in Ambient PM10 in a
Livestock-Dense Area: Implementation of a Land-Use Regression Approach.
AB - BACKGROUND: Results from studies on residential health effects of livestock
farming are inconsistent, potentially due to simple exposure proxies used (e.g.,
livestock density). Accuracy of these proxies compared with measured exposure
concentrations is unknown. OBJECTIVES: We aimed to assess spatial variation of
endotoxin in PM10 (particulate matter <=10MUm) at residential level in a
livestock-dense area, compare simple livestock exposure proxies to measured
endotoxin concentrations, and evaluate whether land-use regression (LUR) can be
used to explain spatial variation of endotoxin. METHODS: The study area (3,000
km2) was located in Netherlands. Ambient PM10 was collected at 61 residential
sites representing a variety of surrounding livestock-related characteristics.
Three to four 2-wk averaged samples were collected at each site. A local
reference site was used for temporal variation adjustment. Samples were analyzed
for PM10 mass by weighing and for endotoxin by using the limulus amebocyte lysate
assay. Three LUR models were developed, first a model based on general livestock
related GIS predictors only, followed by models that also considered species
specific predictors and farm type-specific predictors. RESULTS: Variation in
concentrations measured between sites was substantial for endotoxin and more
limited for PM10 (coefficient of variation: 43%, 8%, respectively); spatial
patterns differed considerably. Simple exposure proxies were associated with
endotoxin concentrations although spatial variation explained was modest
(R2<26%). LUR models using a combination of animal-specific livestock-related
characteristics performed markedly better, with up to 64% explained spatial
variation. CONCLUSION: The considerable spatial variation of ambient endotoxin
concentrations measured in a livestock-dense area can largely be explained by LUR
modeling based on livestock-related characteristics. Application of endotoxin LUR
models seems promising for residential exposure estimation within health studies.
https://doi.org/10.1289/EHP2252.
PMID- 29329103
TI - Analysis of anti-ganglioside antibodies by a line immunoassay in patients with
chronic-inflammatory demyelinating polyneuropathies (CIDP).
AB - BACKGROUND: Unlike for acute immune-mediated neuropathies (IN), anti-ganglioside
autoantibody (aGAAb) testing has been recommended for only a minority of chronic
IN yet. Thus, we used a multiplex semi-quantitative line immunoassay (LIA) to
search for aGAAb in chronic-inflammatory demyelinating polyneuropathy (CIDP) and
its clinical variants. METHODS: Anti-GAAb to 11 gangliosides and sulfatide (SF)
were investigated by LIA in 61 patients with IN (27 typical CIDP, 12 distal
acquired demyelinating polyneuropathy, 6 multifocal-acquired demyelinating
sensory/motor polyneuropathy, 10 sensory CIDP, 1 focal CIDP and 5 multifocal
motoric neuropathy), 40 with other neuromuscular disorders (OND) (15 non-immune
polyneuropathies, 25 myasthenia gravis), 29 with multiple sclerosis (MS) and 54
healthy controls (HC). RESULTS: In contrast to IgG, positive anti-GAAB IgM
against at least one ganglioside/SF was found in 17/61 (27.9%) IN compared to
2/40 (5%) in OND, 2/29 MS (6.9%) and 4/54 (7.4%) in HC (p=0.001). There was a
statistically higher prevalence of anti-sulfatide (aSF) IgM in IN compared to OND
(p=0.008). Further, aGM1 IgM was more prevalent in IN compared to OND and HC
(p=0.009) as well as GD1b in IN compared to HC (p<0.04). The prevalence of aGM1
IgM in CIDP was lower compared to in multifocal motor neuropathy (MMN) (12% vs.
60%, p=0.027). Patients showing aSF, aGM1 and aGM2 IgM were younger compared to
aGAAb negatives (p<0.05). Patients with aSF IgM positivity presented more
frequently typical CIDP and MMN phenotypes (p<0.05, respectively). CONCLUSIONS:
The aGAAb LIA revealed an elevated frequency of at least one aGAAb IgM in
CIDP/MMN patients. Anti-SF, aGM1 and aGM2 IgM were associated with younger age
and anti-SF with IN phenotypes.
PMID- 29329104
TI - Contraception usage among young adult men of a Nigerian university.
AB - Background Family planning services recognize reproductive health as the joint
responsibility of both men and women. Efforts need to be shifted to men's own
sexual health in order to achieve the Millennium Development Goals (MDGs) for
reduction of maternal mortality and HIV transmission. Aims To determine the
methods of contraception used by young adult men and factors that influence their
choice of contraceptive. Methodology A cross-sectional descriptive study was done
using structured questionnaires to extract relevant information from consented
young male adult between ages of 16 and 24 years of Ladoke Akintola University of
Technology (LAUTECH), Ogbomoso, Nigeria. Data was coded using Microsoft Excel and
was analyzed using the SPSS version 17. Results The majority of the respondents
212 (71.6%) had had sexual intercourse. Mean age at first sexual debut was 17.8
+/- 2.5 years. The majority of the respondents 124 (58.5%) did not use any
contraceptives during their first sexual experience and over 1/5th (21.2%) of
respondents had impregnated a partner in the past with the majority, 39 (86.7%)
of such pregnancies resulting in an induced abortion. Frequency of religious
services attendance showed a statistically significant difference with
respondents that were sexually active or had previous sex (p < 0.001). Conclusion
Male involvement and education about contraceptive methods, use and consistency
of contraception could have a drastic reduction in unwanted pregnancies and also
a reduction in abortion complications.
PMID- 29329102
TI - Arsenic Exposure from Drinking Water and Urinary Metabolomics: Associations and
Long-Term Reproducibility in Bangladesh Adults.
AB - BACKGROUND: Chronic exposure to inorganic arsenic from drinking water has been
associated with a host of cancer and noncancer diseases. The application of
metabolomics in epidemiologic studies may allow researchers to identify
biomarkers associated with arsenic exposure and its health effects. OBJECTIVE:
Our goal was to evaluate the long-term reproducibility of urinary metabolites and
associations between reproducible metabolites and arsenic exposure. METHODS: We
studied samples and data from 112 nonsmoking participants (58 men and 54 women)
who were free of any major chronic diseases and who were enrolled in the Health
Effects of Arsenic Longitudinal Study (HEALS), a large prospective cohort study
in Bangladesh. Using a global gas chromatography-mass spectrometry platform, we
measured metabolites in their urine samples, which were collected at baseline and
again 2 y apart, and estimated intraclass correlation coefficients (ICCs). Linear
regression was used to assess the association between arsenic exposure at
baseline and metabolite levels in baseline urine samples. RESULTS: We identified
2,519 molecular features that were present in all 224 urine samples from the 112
participants, of which 301 had an ICC of >=0.60. Of the 301 molecular features,
water arsenic was significantly related to 31 molecular features and urinary
arsenic was significantly related to 74 molecular features after adjusting for
multiple comparisons. Six metabolites with a confirmed identity were identified
from the 82 molecular features that were significantly associated with either
water arsenic or urinary arsenic after adjustment for multiple comparisons.
CONCLUSIONS: Our study identified urinary metabolites with long-term
reproducibility that were associated with arsenic exposure. The data established
the feasibility of using metabolomics in future larger studies.
https://doi.org/10.1289/EHP1992.
PMID- 29329107
TI - Growth and growth hormone: recent papers on efficacy and adverse effects of
growth hormone and World Health Organisation growth standards.
PMID- 29329105
TI - Daily sitting time associated with the risk of metabolic syndrome in Korean
adolescents.
AB - BACKGROUND: This study aimed to investigate the relationship between daily
sitting time and the risk of metabolic syndrome in Korean adolescents. METHODS:
Data from 486 adolescents aged 12-18 years were obtained from national surveys.
Daily sitting time was measured using questionnaires and divided into three
intervals: <8 h; 8-12 h; and >=12 h. RESULTS: The mean daily sitting time and
prevalence of positive metabolic components were 620.9+/-9.9 min/day and 45.5+/
2.7%, respectively. In a multivariate logistic regression analysis, adolescents
who sat longer were more likely to have metabolic components (p<0.05),
independent of age, sex, area of residence, sleeping time and body mass index.
CONCLUSIONS: Longer daily sitting time appears to be associated with an increased
risk of metabolic syndrome in adolescents. These findings highlight the need to
focus on reducing sitting time for all adolescents, not just for those at risk of
obesity.
PMID- 29329106
TI - Genetic mutations associated with neonatal diabetes mellitus in Omani patients.
AB - BACKGROUND: Neonatal diabetes mellitus (NDM) is a rare disorder worldwide where
diabetes is diagnosed in the first 6 months of life. However, Oman has a
relatively high incidence of NDM. METHODS: In this study, we investigated the
genetic etiologies underlying NDM and their prevalence in Oman. We collected a
cohort of 24 NDM patients, with and without genetic diagnosis, referred to our
center from 2007 to 2015. All patients without a genetic diagnosis were tested
for mutations in 23 NDM-associated genes using a custom-targeted next-generation
sequencing (NGS) panel and methylation analysis of the 6q24 locus. RESULTS: A
genetic abnormality was detected in 15/24 (62.5%) of our Omani NDM patients. We
report the detection of 6q24 methylation abnormalities and KCNJ11 mutations for
the first time in Omani NDM patients. Unlike Western populations where NDM is
predominantly due to mutations in the KCNJ11, ABCC8 and INS genes, NDM due to
homozygous GCK gene mutations were most prevalent in Oman, having been observed
in seven out of 15 NDM patients in whom we established the genetic etiology. This
reflects the high degree of consanguinity which makes recessive conditions more
likely. CONCLUSIONS: The results of this study are likely to impact any future
strategy to introduce genetic testing for NDM disorders within the national
healthcare system in Oman.
PMID- 29329108
TI - Cracking novel shared targets between epilepsy and Alzheimer's disease: need of
the hour.
AB - Epilepsy and Alzheimer's disease (AD) are interconnected. It is well known that
seizures are linked with cognitive impairment, and there are various shared
etiologies between epilepsy and AD. The connection between hyperexcitability of
neurons and cognitive dysfunction in the progression of AD or epileptogenesis
plays a vital role for improving selection of treatment for both diseases.
Traditionally, seizures occur less frequently and in later stages of age in
patients with AD which in turn implies that neurodegeneration causes seizures.
The role of seizures in early stages of pathogenesis of AD is still an issue to
be resolved. So, it is well timed to analyze the common pathways involved in
pathophysiology of AD and epilepsy. The present review focuses on similar
potential underlying mechanisms which may be related to the causes of seizures in
epilepsy and cognitive impairment in AD. The proposed review will focus on many
possible newer targets like abnormal expression of various enzymes like GSK
3beta, PP2A, PKC, tau hyperphosphorylation, MMPs, caspases, neuroinflammation and
oxidative stress associated with number of neurodegenerative diseases linked with
epilepsy. The brief about the prospective line of treatment of both diseases will
also be discussed in the present review.
PMID- 29329109
TI - Cluster analysis and subgrouping to investigate inter-individual variability to
non-invasive brain stimulation: a systematic review.
AB - Cluster analysis and other subgrouping techniques have risen in popularity in
recent years in non-invasive brain stimulation research in the attempt to
investigate the issue of inter-individual variability - the issue of why some
individuals respond, as traditionally expected, to non-invasive brain stimulation
protocols and others do not. Cluster analysis and subgrouping techniques have
been used to categorise individuals, based on their response patterns, as
responder or non-responders. There is, however, a lack of consensus and
consistency on the most appropriate technique to use. This systematic review
aimed to provide a systematic summary of the cluster analysis and subgrouping
techniques used to date and suggest recommendations moving forward. Twenty
studies were included that utilised subgrouping techniques, while seven of these
additionally utilised cluster analysis techniques. The results of this systematic
review appear to indicate that statistical cluster analysis techniques are
effective in identifying subgroups of individuals based on response patterns to
non-invasive brain stimulation. This systematic review also reports a lack of
consensus amongst researchers on the most effective subgrouping technique and the
criteria used to determine whether an individual is categorised as a responder or
a non-responder. This systematic review provides a step-by-step guide to carrying
out statistical cluster analyses and subgrouping techniques to provide a
framework for analysis when developing further insights into the contributing
factors of inter-individual variability in response to non-invasive brain
stimulation.
PMID- 29329110
TI - Prediction of sustained harmonic walking in the free-living environment using raw
accelerometry data.
AB - OBJECTIVE: Using raw, sub-second-level accelerometry data, we propose and
validate a method for identifying and characterizing walking in the free-living
environment. We focus on sustained harmonic walking (SHW), which we define as
walking for at least 10 s with low variability of step frequency. APPROACH: We
utilize the harmonic nature of SHW and quantify the local periodicity of the tri
axial raw accelerometry data. We also estimate the fundamental frequency of the
observed signals and link it to the instantaneous walking (step-to-step)
frequency (IWF). Next, we report the total time spent in SHW, number and
durations of SHW bouts, time of the day when SHW occurred, and IWF for 49
healthy, elderly individuals. MAIN RESULTS: The sensitivity of the proposed
classification method was found to be 97%, while specificity ranged between 87%
and 97% and the prediction accuracy ranged between 94% and 97%. We report the
total time in SHW between 140 and 10 min d-1 distributed between 340 and 50
bouts. We estimate the average IWF to be 1.7 steps-per-second. SIGNIFICANCE: We
propose a simple approach for the detection of SHW and estimation of IWF, based
on Fourier decomposition.
PMID- 29329112
TI - Master protocols in lung cancer: experience from Lung Master Protocol.
AB - PURPOSE OF REVIEW: Contemporary advances in the understanding of the molecular
and immunologic basis of metastatic lung cancer have firmly changed its treatment
paradigm to a personalized, biomarker-driven approach. However, the majority of
lung-cancer patients [especially lung squamous cell carcinoma (LUSC)] still do
not have effective targeted therapeutic options. Master protocols, such as Lung
MAP, represent an innovative clinical trial approach designed to accelerate
evaluation of novel biomarker-driven therapies. RECENT FINDINGS: Lung-MAP is an
umbrella trial for advanced LUSC and has been active since 2014. Cumulative
experience from this overarching, multi-institution master protocol has
demonstrated that centralized, real-time biomarker screening is feasible and
substudy modularity is essential for protocol adaptability in a rapidly changing
treatment landscape. In addition, screening and efficacy results from Lung-MAP
affirm that LUSC has several putative drivers but remains difficult to
effectively treat with targeted therapy. SUMMARY: Master protocols are a feasible
and efficient approach for evaluating biomarker-driven therapies in lung cancer.
As we begin to target less common genomic and immunotherapy subtypes, centrally
coordinated clinical trial designs such as Lung-MAP are necessary to rapidly
deliver effective therapies to patients, whereas also maximizing the quality of
research data obtained.
PMID- 29329113
TI - Therapeutic HIV-1 vaccine: time for immunomodulation and combinatorial
strategies.
AB - PURPOSE OF REVIEW: The purpose is to recall some of the key immunological
elements that are at the crossroad and need to be combined for developing a
potent therapeutic HIV-1 vaccine. RECENT FINDINGS: Therapeutic vaccines and
cytokines have been commonly used to enhance and/or recall preexisting HIV-1
specific cell-mediated immune responses aiming to suppress virus replication.
While the vaccine is important to stimulate HIV-1 specific T-cell responses, the
cytokine may support the expansion of the stimulated virus-specific T cells.
Moreover, the current success of immune checkpoint blockers in cancer therapy
render them very attractive to use in HIV-1 infected individuals, with the
objective to preserve the function of HIV-specific T cells from exhaustion and
target directly HIV-1 cell reservoir. More recently, the development of passive
immunotherapy using broad neutralizing HIV antibodies (bNAbs) and their potential
capacity to elicit innate or adaptive HIV-cellular responses, beyond their
neutralizing activity, offers a new opportunity to improve the efficiency of
therapeutic vaccine. These major advances provide the scientific basis for
developing potent combinatorial interventions in HIV-1 infected patients.
SUMMARY: Major advances in our immunological understanding resulting from basic
science and clinical trials studies have paved the way and established a solid
platform to jump over the stumbling blocks that prevent the field from developing
a therapeutic HIV-1 vaccine. It is time for immuno-modulation and combinatorial
strategies towards HIV-1 eradication.
PMID- 29329111
TI - Severe peri-ictal respiratory dysfunction is common in Dravet syndrome.
AB - Dravet syndrome (DS) is a severe childhood-onset epilepsy commonly due to
mutations of the sodium channel gene SCN1A. Patients with DS have a high risk of
sudden unexplained death in epilepsy (SUDEP), widely believed to be due to
cardiac mechanisms. Here we show that patients with DS commonly have peri-ictal
respiratory dysfunction. One patient had severe and prolonged postictal
hypoventilation during video EEG monitoring and died later of SUDEP. Mice with an
Scn1aR1407X/+ loss-of-function mutation were monitored and died after spontaneous
and heat-induced seizures due to central apnea followed by progressive
bradycardia. Death could be prevented with mechanical ventilation after seizures
were induced by hyperthermia or maximal electroshock. Muscarinic receptor
antagonists did not prevent bradycardia or death when given at doses selective
for peripheral parasympathetic blockade, whereas apnea, bradycardia, and death
were prevented by the same drugs given at doses high enough to cross the blood
brain barrier. When given via intracerebroventricular infusion at a very low
dose, a muscarinic receptor antagonist prevented apnea, bradycardia, and death.
We conclude that SUDEP in patients with DS can result from primary central apnea,
which can cause bradycardia, presumably via a direct effect of hypoxemia on
cardiac muscle.
PMID- 29329115
TI - Developing a mitral valve center of excellence.
AB - PURPOSE OF REVIEW: Despite the proven superiority of mitral repair over
replacement for degenerative mitral disease, mitral valve replacement remains
common. Guidelines now recommend referral of patients, particularly those whom
are asymptomatic, to valve centers of excellence, although criteria that define
such centers remain to be established. The purpose of this review is to define
the structure of a mitral center of excellence and to review current clinical
outcomes which are possible in such a center. RECENT FINDINGS: Recently, American
College of Cardiology/American Heart Association as well as the European Society
of Cardiology/European Association of Cardiothoracic Surgery guidelines define
mitral centers of excellence as either centers in which the likelihood of
successful and durable repair exceeds 95% and with an operative mortality risk of
less than 1% (American College of Cardiology/American Heart Association
definition) or centers with high repair rates, low operative mortality, and a
record of durable results (European Society of Cardiology/European Association of
Cardiothoracic Surgery definition). There is however less clarity about the
structure and function of a center that achieves these outcomes. SUMMARY: The
importance of centers of excellence in mitral valve surgery are now well
recognized, and this review will highlight the key components and outcomes of an
established mitral valve reference center.
PMID- 29329114
TI - Synovial sarcomas of the upper aero-digestive tract: is there a role for
conservative surgery?
AB - PURPOSE OF REVIEW: To present the current state of knowledge concerning the role
of conservative surgery in the treatment of synovial sarcomas of the upper aero
digestive tract (UADT). RECENT FINDINGS: The wider experience on synovial
sarcomas involving the extremities and the results of retrospective reports
focused on head and neck synovial sarcomas tend to justify a conservative
surgical approach when dealing with tumors involving the UADT. SUMMARY: UADT
synovial sarcomas is an extremely rare clinical entity (only around 50 cases
reported in the literature, with four more herein presented from our own surgical
series), with no clear guidelines concerning its treatment. Resection should be
aimed to an en-bloc removal of the tumor within uninvolved surgical margins. In
fit patients, a conservative surgical approach should be preferred if it does not
interfere with a complete resection and reasonable functional outcomes. Adjuvant
treatments (radiotherapy and/or chemotherapy) are frequently needed in view of
the aggressive behavior of such tumor, but they should be balanced according to
patient's characteristics and tumor risk factors (grade, size, and previous
treatments).
PMID- 29329116
TI - Concussion Symptom Underreporting Among Incoming National Collegiate Athletic
Association Division I College Athletes.
AB - OBJECTIVE: Accurate diagnosis of sport-related concussions relies heavily on
truthful self-reporting of symptom severity. Previous studies have emphasized
lack of knowledge as a factor in symptom nondisclosure. This study sought to
examine concussion knowledge and the relationship of knowledge to reasons for
symptom nondisclosure. DESIGN: Cross-sectional study. SETTING: Data were
collected during preparticipation athletic evaluations via electronic survey.
PARTICIPANTS: One hundred fifty-six incoming National Collegiate Athletic
Association Division I student-athletes. MAIN OUTCOME MEASURES: Survey items
included previous concussion diagnosis, concussion fact and symptom knowledge,
reasons and situational contexts for nondisclosure, and stakeholder attitudes.
RESULTS: Participants, on average, had substantial concussion symptom and fact
knowledge. Unexpectedly, participants with higher concussion fact knowledge
endorsed more reasons that athletes may hide symptoms. Concussion symptom
knowledge was unrelated to reasons for nondisclosure. Athletes believed that
symptom reporting was less likely in high-stakes versus low-stakes situations and
consistently identified their teammates as holding attitudes that support
underreporting and athletic trainers as engaging in behaviors that support player
safety. CONCLUSIONS: Greater concussion knowledge did not reduce the number of
reasons that participants viewed as drivers for concussion nondisclosure. In
other words, participants understood why athletes choose to hide symptoms even
when they also understood the symptoms, risks, sequelae, and consequences of
concussion (and potential harm of nondisclosure). Situational contexts and
important stakeholder attitudes also appeared to importantly influence symptom
disclosure decisions. A multifaceted approach that goes beyond current
educational strategies to addresses situational, social, and athletic pressures
may be needed to initiate a widespread cultural shift away from concussion
nondisclosure.
PMID- 29329118
TI - CE: Managing Sepsis and Septic Shock: Current Guidelines and Definitions.
AB - : Sepsis is a leading cause of critical illness and hospital mortality. Early
recognition and intervention are essential for the survival of patients with this
syndrome. In 2002, the Society of Critical Care Medicine (SCCM) and the European
Society of Intensive Care Medicine (ESICM) launched the Surviving Sepsis Campaign
(SSC) to reduce overall patient morbidity and mortality from sepsis and septic
shock by driving practice initiatives based on current best evidence. The SSC
guidelines have been updated every four years, with the most recent update
completed in 2016. The new guidelines have increased the focus on early
identification of infection, risks for sepsis and septic shock, rapid antibiotic
administration, and aggressive fluid resuscitation to restore tissue perfusion.In
2014, the SCCM and the ESICM convened a task force of specialists to reexamine
the definitions of terms used to identify patients along the sepsis continuum. In
2016, this task force published the Third International Consensus Definitions for
Sepsis and Septic Shock (Sepsis-3). The new definitions and recommendations
included tools, based on an updated understanding of the pathobiology of sepsis,
that can be used to predict adverse outcomes in patients with infection.This
article discusses the new SSC treatment guidelines, changes in the sepsis bundle
interventions, and the Sepsis-3 definitions and tools, all of which enable nurses
to improve patient outcomes through timely collaborative action.
PMID- 29329119
TI - Effects of Valproic Acid on Morphology, Proliferation, and Differentiation of
Mesenchymal Stem Cells Derived From Human Gingival Tissue.
AB - PURPOSE: Valproic acid (VPA), a histone deacetylase inhibitor, has been shown to
affect cell growth and differentiation in various in vitro and in vivo models.
The aim of this study is to evaluate the effects of VPA on viability and
osteogenic differentiation of mesenchymal stem cells derived from the human
gingival tissue. MATERIALS AND METHODS: Stem cells derived from the gingiva were
grown in the presence of VPA at concentrations ranging from 0.125 to 8 mM. Cell
morphology was assessed on days 3, 5, and 7, and cell proliferation was analyzed
on the same days using a Cell Counting Kit-8 (CCK-8). Alizarin Red-S staining was
used to assess differentiation of the stem cells. RESULTS: The control group
showed a normal fibroblast morphology when cultured in growth media. The shape of
cells in the 8 mM group was more flat than cells in other groups, and fewer cells
were present. A statistically significant decrease in cell proliferation was seen
in the 8 mM group. Results of Alizarin Red-S staining showed a significant
decrease in mineralization in the 8 mM group. CONCLUSIONS: Taken together, this
study demonstrated that VPA, at the tested concentrations, decreases the
viability of stem cells derived from the human gingiva. The decreases in
osteogenic differentiation were achieved via the decrease of Rux2 expression. The
concentration and application time of VPA treatment should be meticulously
controlled to minimize any detrimental effects.
PMID- 29329117
TI - CE: Original Research: Physical Activity Among Chinese American Immigrants with
Prediabetes or Type 2 Diabetes.
AB - : : Background: Although the benefits of aerobic exercise and strength training
for patients with type 2 diabetes have been studied extensively, research on
physical activity among Chinese American immigrants diagnosed with prediabetes or
type 2 diabetes has been limited. PURPOSE: We sought to learn more about this
population's knowledge of physical activity, the types and intensity levels
performed, and the barriers to such activity. DESIGN AND METHODS: A concurrent
mixed-methods design was used. The short version of the International Physical
Activity Questionnaire-Chinese was used to quantitatively measure participants'
levels of exercise intensity. Semistructured face-to-face interviews were
conducted to obtain qualitative information regarding participants' knowledge
about physical activity, the types performed, and the barriers to such activity.
RESULTS: A total of 100 Chinese American immigrants were recruited for the study
from January to July 2012 in New York City. On average, participants had lived
with a diagnosis of prediabetes or type 2 diabetes for 3.3 years and had lived in
the United States for 21.5 years. Energy expenditure was measured in metabolic
equivalent of task (MET) units; intensity was measured in cumulative MET-minutes
per week. The mean total intensity score was 2,744 MET-minutes per week. This was
achieved mainly through walking. The mean intensity score for walking was 1,454
MET-minutes per week; the mean duration was 79 minutes per day. Vigorous physical
activity was least common. The mean intensity score for vigorous physical
activity was 399 MET-minutes per week, and the mean duration was 17 minutes per
week. Regarding types of physical activity, the most common were housekeeping,
walking up stairs, and taking walking or stretching breaks every hour during the
workday. Based on the interviews, three themes emerged regarding barriers to
moderate or vigorous physical activity: insufficient education about physical
activity, health concerns about physical activity, and work-related barriers to
physical activity. CONCLUSIONS: The majority of Chinese American immigrants with
prediabetes or type 2 diabetes do not engage in sufficient physical activity,
performing at a rate significantly below that of the general U.S. POPULATION:
Increases in the intensity and duration of physical activity should be promoted
as part of diabetes management for Chinese American immigrants.
PMID- 29329120
TI - Re-osseointegration of Dental Implants After Periimplantitis Treatments: A
Systematic Review.
AB - PURPOSE: This review considers possible surgical treatment modalities for induced
periimplantitis to regain re-osseointegration as reported in the recent
literature. MATERIALS AND METHODS: Electronic searches in MEDLINE/PubMed and
Google Scholar databases were performed on experimental studies considering
induced periimplantitis and attempts to achieve re-osseointegration from 2003 up
to December 2016. Conflicts about articles were solved by authors' discussion.
RESULTS: A total of 15 studies of 159 were finally included in the review.
DISCUSSION: Various implant surface decontamination techniques chemical and/or
mechanical have been used either alone or simultaneously with/without guided bone
regeneration. Despite the access-flap surgery, it was observed that application
of single decontamination measure either chemical or mechanical was not adequate
to provide a better treatment outcome. Laser application such as CO2, diode, and
Er: YAG has been a new treatment approach used for periimplantitis treatment. Er:
YAG laser had showed no implant surface alteration and provided favorable
environment for re-osseointegration. CONCLUSION: Promising results were observed
in the studies that used combination of bone substitutes together with guided
bone regeneration for the regenerative therapy. Regarding implant surfaces,
better re-osseointegration was observed with rough implant surfaces rather than
smooth ones.
PMID- 29329121
TI - Technique for Preparing Ultrathin and Nanothin Descemet Stripping Automated
Endothelial Keratoplasty Tissue.
AB - PURPOSE: To describe and report outcomes of our single-pass microkeratome
technique for preparation of ultrathin (UT, <=100 MUm) and nanothin (NT, <=50
MUm) Descemet stripping automated endothelial keratoplasty (DSAEK) grafts.
METHODS: To prepare NT-DSAEK grafts, a pachymetry nomogram specific to each
technician and individual microkeratome head was developed based on accumulated
precut and postcut pachymetry data from previous DSAEK grafts. Mean graft
thickness as well as precut and postcut endothelial cell counts (ECCs) of NT
DSAEK, UT-DSAEK, and Descemet membrane endothelial keratoplasty (DMEK) grafts
between July 2015 and July 2017 were calculated and compared statistically.
Endothelial cell loss was evaluated using calcein AM stains and ImageJ analysis.
Postcut graft thickness and rates of perforation/tissue loss for NT-DSAEK grafts
between May and July 2017 were calculated to determine overall graft preparation
success rates. RESULTS: Mean postcut graft thickness for all grafts within the NT
range was 41.0 +/- 6.4 MUm (range 26-50 MUm). Mean ECC did not differ between NT
DSAEK, UT-DSAEK, and DMEK grafts (P = 0.759 and 0.633, respectively). The overall
tissue loss rate from attempted NT-DSAEK was 4.8%. Excluding cases of
perforation, the chance of achieving NT thickness was 60% and within the
traditional UT range was 100%. CONCLUSIONS: We propose the term "NT-DSAEK" for
grafts <=50 MUm. The described nomogram allows for standardized creation of NT
grafts with a low tissue loss rate. This technique is safe and does not result in
significant ECC loss compared with UT-DSAEK and DMEK grafts. Further studies are
necessary to corroborate the postsurgical results of NT grafts.
PMID- 29329122
TI - Some of Us Stay.
PMID- 29329123
TI - Golf Injuries: Epidemiology, Pathophysiology, and Treatment.
AB - Increasing numbers of people are playing golf. Golf is a unique sport in that the
ability to participate at a high level is not limited by age. In addition,
participants tend to play more rather than less as they grow older. Injuries can
occur at any point during the golf swing, from takeaway through follow-through.
Upper extremity injuries can affect the hands, elbow, and shoulder and are
usually a result of the golf swing at impact. Injuries are also common in the
lower back as well as the lower extremities. Most injuries are the result of
overuse and poor swing mechanics. When treating golfers, it is important to have
a good understanding of the biomechanics and forces of the golf swing to diagnose
and manage the vast spectrum of injuries incurred in this sport.
PMID- 29329124
TI - Septic Arthritis of the Wrist.
AB - Septic arthritis of the wrist is an uncommon condition, but one that can result
in substantial morbidity. Timely identification and treatment is critical to
patient care. No serum laboratory values have been shown to consistently confirm
wrist joint infection. Thus, diagnosis is made based mainly on a thorough patient
history, physical examination, and joint aspiration. When infection is suspected,
aspiration of the wrist should be performed to confirm the diagnosis. Broad
spectrum antibiotics and joint aspiration or surgery are required to manage the
infection and prevent sequelae.
PMID- 29329125
TI - On the Horizon From the ORS.
PMID- 29329126
TI - Case of Congenital Self-Healing Reticulohistiocytosis Expanding the Spectrum of
Blueberry Muffin Baby.
AB - Congenital self-healing reticulohistiocytosis (CSHRH) is a benign, rare variant
of histiocytosis. This condition can present phenotypically as blueberry muffin
baby. This is the case of a male neonate with skin involvement of papulonodular
violaceous lesions, which resolved spontaneously. The diagnosis of CSHRH is
confirmed using histopathology and immunohistochemistry.
PMID- 29329127
TI - Cutis Laxa Acquisita After Urticarial Vasculitis in SLE Patients.
AB - Cutis laxa is a rare connective tissue disease involving damage to dermal elastic
fibers creating a clinical appearance of loose, sagging skin. The condition can
be either acquired or genetic. Autoimmune diseases, neoplasms, infections, and
medications have been proposed as the cause of, or in association with, the
acquired form. In nearly 50% of cases, erythematous plaques present before the
onset of cutis laxa. Separately, urticarial vasculitis and systemic lupus
erythematosus have been linked to cutis laxa acquisita. Our case is the first in
the literature documenting a coexistence of cutis laxa acquisita,
hypocomplementemic urticarial vasculitis, and systemic lupus erythematosus.
PMID- 29329128
TI - Expanding the Morphologic Heterogeneity of Stromal Changes in Molluscum
Contagiosum Infection.
PMID- 29329129
TI - Primary Cutaneous Spindle Cell Squamous Carcinoma Expressing Smooth Muscle Actin:
Diagnostic Pitfalls.
AB - Alpha smooth muscle actin (SMA) belongs to the actin proteins. It is a known
immunohistochemical marker for tumors of mesenchymal origin. There have been
reports of expression of SMA in certain epithelial malignancies in the head and
neck and genital regions. In this study, the authors report a primary cutaneous
spindle cell squamous carcinoma expressing SMA. Both high- and low-molecular
weight keratins and p63 were positive, and S100 protein, SOX10, MART-1/Melan-A,
and muscle-specific actin stains were negative. This case highlights that an
epithelial tumor could express a mesenchymal marker, thereby making the diagnosis
problematic.
PMID- 29329130
TI - Disseminated Warty Papules and Plaques: Question.
PMID- 29329131
TI - ALK Gene Fusions in Epithelioid Fibrous Histiocytoma: A Study of 14 Cases, With
New Histopathological Findings.
AB - Previous studies showed that ALK is often positive in epithelioid fibrous
histiocytoma (EFH). Two cases of EFH with ALK gene fusions have been recorded.
Our objective was to study a series of EFH to present histopathological
variations of EFH, identify novel ALK gene fusions, and determine whether there
is a correlation between histopathological features and particular gene. We
investigated 14 cases of EFH, all ALK immunopositive. The cases were assessed
histopathologically as well as for ALK and TFE-3 rearrangements using FISH and
ALK gene fusions using next-generation sequencing. The analysis of the sequencing
results was performed using the Archer Analysis software (v5; ArcherDX Inc). The
study group consisted of 8 female and 6 male patients, ranging in age from 18 to
79 years (mean 42 years; median 37.5 years). All presented with a solitary
lesion. Microscopically, most lesions were polypoid and composed of epithelioid
cells with ample cytoplasm. In addition, a variable number of bi-, tri-, or
multinucleated, spindled, multilobated, cells with eccentric nuclei, cells with
nuclear pseudoinclusions, mucinous, and grooved cells were admixed. In 5 cases,
the predominant epithelioid cell component consisted of rather small cells,
whereas spindled cells dominated in 3 cases. Of these, 2 lesions were composed
rather of pale eosinophilic to clear cells, occasioning a resemblance to PEComa
or leiomyoma. Immunohistochemically, all cases expressed ALK and 11 were positive
for TFE-3. The break apart test for ALK was positive in 11 cases, whereas
specimens from the remaining 3 cases were not analyzable. ALK genes fusions were
found in all but 3 cases and included SQSTM1-ALK (3), VCL-ALK (3), TMP3-ALK (2),
PRKAR2A-ALK (1), MLPH-ALK (1), and EML4-ALK (1). No correlation between
histological features and type of ALK fusion was found. TFE-3 break apart test
was negative. It is concluded that ALK-immunopositive EFH shows ALK gene fusions
that involve various protein-coding genes, implicated in a variety of biological
processes. Rare variants of EFH rather consist of spindled "non-epithelioid"
cells.
PMID- 29329132
TI - Cutaneous Nodules and Violaceous Patches on the Legs.
PMID- 29329133
TI - Cutaneous Angiosarcoma of the Eyelid Mimicking Morbihan Disease.
AB - BACKGROUND: Cutaneous angiosarcoma presents clinically in numerous ways, and can
be mistaken for a different clinical entity, particularly when arising at unusual
anatomic locations such as the eyelid. CASE PRESENTATION: A 57-year-old woman
presented with a 1-year history of eyelid swelling. Concurrent imaging was also
suggestive of an edematous process. Multiple superficial biopsies showed
nonspecific dermal inflammation and interstitial edema. A diagnosis of Morbihan
disease (chronic and idiopathic lymphedema of the eyelid) was rendered, and the
patient was treated with compression and local therapy without clinical
improvement. Three years after initial presentation, a diagnostic blepharoplasty
was performed revealing a deep dermal vascular proliferation composed of
anastomosing vascular channels with an atypical endothelial lining. A diagnosis
of cutaneous angiosarcoma was ultimately made. CONCLUSIONS: This case illustrates
a unique presentation of cutaneous angiosarcoma and the implications of different
biopsy techniques in acquiring the correct diagnosis.
PMID- 29329134
TI - Asymptomatic Acquired Facial Hyperpigmentation.
PMID- 29329135
TI - Clinician Perceptions of the Importance of Hospital Discharge Components for
Children.
AB - BACKGROUND: Discharging hospitalized children involves several different
components, but their relative value is unknown. We assessed which discharge
components are perceived as most and least important by clinicians. METHODS:
March and June of 2014, we conducted an online discrete choice experiment (DCE)
among national societies representing 704 nursing, physician, case management,
and social work professionals from 46 states. The DCE consisted of 14 discharge
care components randomly presented two at a time for a total of 28 choice tasks.
Best-worst scaling of participants' choices generated mean relative importance
(RI) scores for each component, which allowed for ranking from least to most
important. RESULTS: Participants, regardless of field or practice setting,
perceived "Discharge Education/Teach-Back" (RI 11.1 [95% confidence interval, CI:
11.0-11.3]) and "Involve the Child's Care Team" (RI 10.6 [95% CI: 10.4-10.8]) as
the most important discharge components, and "Information Reconciliation" (RI 4.1
[95% CI: 3.9-4.4]) and "Assigning Roles/Responsibilities of Discharge Care" (RI
2.8 [95% CI: 2.6-3.0]) as least important. CONCLUSIONS: A diverse group of
pediatric clinicians value certain components of the pediatric discharge care
process much more than others. Efforts to optimize the quality of hospital
discharge for children should consider these findings.
PMID- 29329136
TI - Glaucoma Implant Tube Lumen Obstruction Visualized Using Anterior Segment Optical
Coherence Tomography.
AB - We report a case of glaucoma implant tube lumen obstruction visualized with
anterior segment optical coherence tomography (ASOCT) and present its surgical
management. The patient was a 66-year-old man with refractory glaucoma associated
with traumatic aphakia in the right eye after trabeculectomy, several bleb
needling procedures, and scleral fixation of the intraocular lens with pars plana
vitrectomy. Finally, we performed Baerveldt implantation at the pars plana of the
temporal inferior quadrant with a several Sherwood slit. However, his intraocular
pressure (IOP) was >30 mm Hg despite maximum medication for several weeks. We
attempted second vitrectomy and completely removed vitreous around the tube tip;
however, his IOP remained around 40 mm Hg for several days after the surgery.
Therefore, we suspected tube obstruction at the extraocular point of the tube
lumen and used ASOCT for assessment. ASOCT revealed material in the tube lumen.
We pulled out the tube and then crushed and extruded the obstructing material
from the tube tip. We then refixed the tube at the same place and achieved good
IOP control after the surgery. Our findings indicate that ASOCT is useful for
diagnosing glaucoma implant tube lumen obstruction and surgical decision-making.
PMID- 29329137
TI - Macular and Multifocal PERG and FD-OCT in Preperimetric and Hemifield Loss
Glaucoma.
AB - PURPOSE: To evaluate the ability of macular and multifocal (mf) pattern
electroretinogram (PERG) to differentiate preperimetric glaucoma (PG) and
glaucoma with hemifield loss (GHL) from controls, to compare the discrimination
ability of PERG and fourier-domain optical coherence tomography (FD-OCT), and to
assess the relationship between measurements. PATIENTS AND METHODS: Standard
automated perimetry, steady-state and transient PERG and mfPERG measurements were
obtained from PG (n=14, 24 eyes), GHL (n=5, 7 eyes), and controls (n=19, 22
eyes). Circumpapillary retinal nerve fiber layer (cpRNFL), full-thickness macula,
and segmented macular layer thicknesses on FD-OCT were investigated. Measurements
were compared using mixed effects linear models. The relationships between
measurements and the diagnostic performance of each technology were assessed.
RESULTS: Compared with controls, average P50 peak time transient PERG responses
were reduced in PG and GHL, whereas average latency and amplitude steady-state
and mfPERG responses were abnormal only in GHL. cpRNFL and macular thickness
measurements in PG and GHL differed significantly from controls. A significant
relationship was found between PERG and most FD-OCT or SAP parameters. Partial
least squares discriminant analysis revealed that OCT parameters, along with
mfPERG and transient PERG parameters had similar ability to discriminate PG and
GHL from healthy controls. CONCLUSIONS: PERG and OCT parameters may be abnormal,
with significant correlations between measurements, in PG eyes. Both technologies
may be useful for detection of early glaucoma.
PMID- 29329138
TI - Relationship of Macular Thickness and Function to Optical Microangiography
Measurements in Glaucoma.
AB - PURPOSE: The purpose of this article was to evaluate the relationship between
macular optical microangiography (OMAG), ganglion cell-inner plexiform layer
(GCIPL) thickness, and visual sensitivity measurements of different macular
sectors in primary open-angle glaucoma. METHODS: In a cross-sectional study, 39
eyes of 26 primary open-angle glaucoma patients underwent optical coherence
tomography imaging and 10-2 visual field examination of the macula in the same
session. Linear regression models were used to evaluate the relationships between
OMAG, GCIPL thickness, and visual sensitivity measurements in different macular
sectors. Strength of relationship was reported as coefficient of determination
(R). RESULTS: R values for the associations between OMAG and GCIPL thickness
measurements ranged from 0.37 in the temporal sector to 0.56 in the inferior
macular sector. R values for the association between OMAG and visual sensitivity
measurements ranged from 0.23 in the superior to 0.53 in the inferior macular
sector. R values for the association between GCIPL thickness and visual
sensitivity measurements ranged from 0.15 in the superior to 0.62 in the temporal
sector. CONCLUSIONS: The strongest associations between OMAG, GCIPL thickness,
and visual sensitivity measurements were found in the inferior macular sector.
The association of OMAG with GCIPL thickness measurements was as strong as the
association between OMAG and visual sensitivity measurements in the inferior
macular sector.
PMID- 29329139
TI - Diagnostic Ability and Structure-function Relationship of Peripapillary Optical
Microangiography Measurements in Glaucoma.
AB - PURPOSE: The aim of this study was to evaluate the diagnostic abilities of
peripapillary optical microangiography (OMAG) measurements in eyes with primary
open-angle glaucoma (POAG) and to evaluate the relationship of these measurements
with retinal nerve fiber layer (RNFL) thickness and visual sensitivities in
different peripapillary sectors. METHODS: In a cross-sectional study, 97 eyes of
57 control subjects and 101 eyes of 66 POAG patients underwent OMAG and RNFL
imaging with optical coherence tomography. POAG was diagnosed on the basis of the
masked evaluation of optic disc stereo photographs. Area under receiver operating
characteristic curves and sensitivities at 90% specificity of the OMAG and RNFL
thickness measurements in different peripapillary sectors were evaluated.
Association between OMAG, RNFL thickness, and visual sensitivity measurements
were evaluated using fractional polynomial regression models. RESULTS: All OMAG
and RNFL measurements were significantly less in the POAG compared with the
control eyes. Diagnostic abilities of the best OMAG measurement (inferior sector
vessel length density, area under receiver operating characteristic curves: 0.84,
sensitivity at 90%, specificity: 65%) were significantly less (P<0.05) than that
of the best RNFL measurement (inferior sector RNFL thickness, 0.94 and 81%).
Inferior sector vessel length density showed the strongest association with
inferior sector RNFL thickness (R=0.66, P<0.001) and the superior sector visual
sensitivity loss (R=0.21, P=0.006). CONCLUSIONS: The inferior sector OMAG
measurements had the best diagnostic ability in glaucoma and the strongest
association with RNFL and the visual sensitivity measurements. Diagnostic ability
of OMAG measurements, however, were significantly less than the RNFL thickness
measurements.
PMID- 29329140
TI - Slit-lamp Needling of the Anterior Capsule for Aqueous Misdirection After
Hyaloido-zonulectomy and Iridectomy.
AB - INTRODUCTION: We present a case of persistent aqueous misdirection, after Ahmed
glaucoma valve surgery, despite undergoing an anterior vitrectomy with hyaloido
zonulectomy and iridectomy. CASE REPORT: A 73-year-old female patient, 4 months
after phacotrabeculectomy, was referred with persistent high intraocular pressure
(IOP). Postoperatively, she developed aqueous misdirection with a flat anterior
chamber (AC) but with an IOP of 15 mm Hg. On presentation, her AC was shallow
with peripheral iris-cornea touch, and her IOP was 39 mm Hg. Posterior Nd:Yag
capsulotomy with disruption of anterior hyaloid face partially deepened the AC.
With failure of the trabeculectomy and high IOP, an Ahmed valve was placed. On
the first operative day the AC was deep with an IOP of 10 mm Hg. On day 6 the
patient presented with pain, flat AC, and an IOP of 10 mm Hg. Fundus examination
revealed no choroidal effusion. Despite repeated reformation with viscoelastic,
the AC failed to deepen. An anterior vitrectomy with hyaloido-zonulectomy was
performed. Initially, the AC was deep, but, a few days later, it was flat.
Multiple reformations and vitreous tap failed to keep the AC deep. A 30-G needle
was passed at the slit lamp across the temporal cornea, iris, and anterior
capsule into the anterior vitreous cavity. The needle was then partially
withdrawn and used to create a space between the intraocular lens and anterior
capsule. This immediately deepened the AC and remained so for the duration of
follow-up (4 mo). CONCLUSION: Slit-lamp needling of the anterior lens capsule can
be successfully performed to help resolve a persistent case of aqueous
misdirection after anterior vitrectomy.
PMID- 29329141
TI - Precision of Optic Nerve Head and Retinal Nerve Fiber Layer Parameter
Measurements by Spectral-domain Optical Coherence Tomography.
AB - PURPOSE: The aim of this study was to assess the repeatability and
reproducibility (R&R) of Bruch membrane opening based on minimum rim width (BMO
MRW), minimum rim area (BMO-MRA) and peripapillary retinal nerve fiber layer
thickness (RNFLT) with the Spectralis optical coherence tomography (Heidelberg
Engineering) for normal and glaucoma subjects. Precise measurement of these
parameters can support detection of structural glaucomatous damage and
progression. METHODS: This cross-sectional study included 16 healthy controls and
16 patients with glaucoma. One eye was randomly selected and included in this
study. Subjects underwent 1 baseline and 3 follow-up measurements, using 3
different Spectralis optical coherence tomography devices in randomized order,
each operated by a single operator. Outcome measures were global and sectorial
averages of BMO-MRW and BMO-MRA, and of peripapillary RNFLT obtained from
12/14/16-degree circle scans. Coefficients of variation (COV) were calculated and
a mixed-effects analysis of variance was performed to compare R&R between
devices. RESULTS: COVs of global and sectorial BMO-MRW measurement under
repeatability conditions ranged from 0.51% to 1.7% (normal, 0.62% to 1.3%;
glaucoma, 0.64% to 2.3%). Respective COVs under reproducibility conditions ranged
from 0.89% to 1.9% (normal, 0.77% to 2.8%; glaucoma, 1.1% to 2.6%). COVs of
global and sectorial RNFLT measurements under repeatability conditions ranged
from 0.5% to 2.8%. Respective COVs under reproducibility conditions ranged from
1.6% to 3.5%. CONCLUSIONS: For R&R, the COVs of measured parameters were by trend
higher for glaucoma eyes compared with normal controls. The BMO-MRW measurement
system has an excellent precision taking into account that major and minor
corrections of segmentation have to be done by the examiner before evaluation.
PMID- 29329142
TI - Whole-genome methylation profiling of peripheral blood mononuclear cell for acute
exacerbations of chronic obstructive pulmonary disease treated with
corticosteroid.
AB - OBJECTIVE: Although association studies in the general population may be relevant
for determining susceptibility to chronic obstructive pulmonary disease (COPD),
they may be less applicable for pharmacogenetics research in participants who
have already acquired the disease. PATIENTS AND METHODS: A genome-wide
methylation profiling (generated by HumanMethylation450 BeadChips study was
performed on peripheral blood mononuclear cells of 24 patients with AECOPD (acute
exacerbation COPD), with good and poor responsiveness to standard corticosteroid
treatment. Pyrosequencing was used to replicate the selected CpG sites in 50
patients with AECOPD with standard corticosteroid treatment. RESULTS: The results
showed the patients with AECOPD with good and poor response to standard
corticosteroid treatment have a distinct DNA methylation pattern. A total of 23
CpG loci located in 19 known gene regions, including gene-body and promoter,
appeared to be significantly differentially methylated. Replication by
pyrosequencing revealed that one CpG site in PSMD8 showed the same trend of
differential methylation and reached to statistical significance as the
microarray result. CONCLUSION: Our preliminary findings provide evidence for
molecular heterogeneity in patients with AECOPD, which may contribute to
significant differences in their response to COPD treatment.
PMID- 29329143
TI - Wellness, stress, balance...and resilience.
PMID- 29329144
TI - Cybersecurity matters.
AB - How to safeguard patient and other sensitive data.
PMID- 29329145
TI - Orthopaedic Management of Leg-length Discrepancy in Proteus Syndrome: A Case
Series.
AB - INTRODUCTION: Proteus syndrome (PS) is a rare mosaic disorder comprising
asymmetric bony and soft tissue overgrowth leading to significant morbidity.
Placement of growth inhibition hardware with subsequent epiphyseal arrest
improves leg-length and angular deformities in pediatric patients without PS. The
purpose of this study was to review the surgical approach and present outcomes,
complications, and recommendations in 8 patients with PS and leg-length
discrepancy (LLD). METHODS: We conducted a retrospective chart review of 8
patients with PS whose primary reason for surgery was LLD. Patients were eligible
if they met clinical diagnostic criteria for PS and if the National Institutes of
Health team performed at least 1 of their surgical interventions between 2005 and
2015. Surgical techniques included growth inhibition, with tension band plates,
applied >=1 times, and epiphyseal arrest. RESULTS: Eight patients, followed for
an average of 4.6 years (range, 1.0 to 7.1 y) after the index procedure, were
included in this analysis. Average age at first LLD surgery was 9.4 years (range,
6.1 to 13.6 y); the average LLD was 3.4 cm (range, 0.4 to 7.0 cm) at
presentation, and 5.0 cm (range, 1.8 to 10.0 cm) at the time of the first LLD
surgery. Participants underwent 23 total surgeries (range, 1 to 5 per patient)
and 7 patients have completed surgical intervention. For the 7 patients who did
not require overcorrection the average LLD at the last clinical encounter was 2.6
cm (range, 0.6 to 7.2 cm). We encountered 2 complications: 2 patients developed
mild knee valgus, which responded to standard guided growth techniques.
CONCLUSIONS: This case series suggests that growth inhibition and epiphyseal
arrest in children with PS can reduce LLD with few complications. Careful
monitoring, rapid mobilization, deep venous thrombosis prophylaxis, and
sequential compression devices were also integral elements of our surgical
protocol. LEVEL OF EVIDENCE: Level IV.
PMID- 29329146
TI - National Prevalence and Effects of Multiple Chemical Sensitivities.
AB - OBJECTIVE: The aim of this study was to assess the prevalence of multiple
chemical sensitivities (MCS), its co-occurrence with asthma and fragrance
sensitivity, and effects from exposure to fragranced consumer products. METHODS:
A nationally representative cross-sectional population-based sample of adult
Americans (n = 1137) was surveyed in June 2016. RESULTS: Among the population,
12.8% report medically diagnosed MCS and 25.9% report chemical sensitivity. Of
those with MCS, 86.2% experience health problems, such as migraine headaches,
when exposed to fragranced consumer products; 71.0% are asthmatic; 70.3% cannot
access places that use fragranced products such as air fresheners; and 60.7% lost
workdays or a job in the past year due to fragranced products in the workplace.
CONCLUSION: Prevalence of diagnosed MCS has increased over 300%, and self
reported chemical sensitivity over 200%, in the past decade. Reducing exposure to
fragranced products could help reduce adverse health and societal effects.
PMID- 29329147
TI - Multisource Feedback and Narrative Comments: Polarity, Specificity,
Actionability, and CanMEDS Roles.
AB - INTRODUCTION: Multisource feedback is a questionnaire-based assessment tool that
provides physicians with data about workplace behaviors and may combine numeric
and narrative (free-text) comments. Little attention has been paid to wording of
requests for comments, potentially limiting its utility to support physician
performance. This study tested the phrasing of two different sets of questions.
METHODS: Two sets of questions were tested with family physicians, medical and
surgical specialists, and their medical colleague and coworker respondents. One
set asked respondents to identify one thing the participant physician does well
and one thing the physician could target for action. Set 2 questions asked what
does the physician do well and what might the physician do to enhance practice.
Resulting free-text comments provided by respondents were coded for polarity
(positive, neutral, or negative), specificity (precision and detail),
actionability (ability to use the feedback to direct future activity), and
CanMEDS roles (competencies) and analyzed descriptively. RESULTS: Data for 222
physicians (111 physicians per set) were analyzed. A total of 1824 comments
(8.2/physician) were submitted, with more comments from coworkers than medical
colleagues. Set 1 yielded more comments and were more likely to be positive, semi
specific, and very actionable than set 2. However, set 2 generated more very
specific comments. Comments covered all CanMEDS roles with more comments for
collaborator and leader roles. DISCUSSION: The wording of questions inviting free
text responses influences the volume and nature of the comments provided.
Individuals designing multisource feedback tools should carefully consider
wording of items soliciting narrative responses.
PMID- 29329148
TI - Self-reported Health Status Differs for Amazon's Mechanical Turk Respondents
Compared With Nationally Representative Surveys.
AB - BACKGROUND: Amazon's Mechanical Turk (MTurk) platform has become a data source
for peer-reviewed academic research publications, with over 24,000 Google Scholar
search results. Although well-developed and supportive in other disciplines, the
literature in health and medicine comparing results from samples generated on
MTurk to gold standard, nationally representative health and medical surveys is
beginning to emerge. OBJECTIVE: To compare the demographic, socioeconomic, and
self-reported health status variables in an MTurk sample to those from 2
prominent national probability surveys, including the Medical Expenditure Panel
Survey (MEPS) and the Behavioral Risk Factor Surveillance System (BRFSS).
RESEARCH DESIGN: We analyze weighted and unweighted tabulations of the MTurk,
MEPS, and BRFSS. Wald tests identify statistical significance. MEASURES:
Demographic, socioeconomic, and health status variables in an adult MTurk sample
collected in 2016 (n=1916), the 2015 MEPS household survey component (n=21,210),
and the 2015 BRFSS (n=283,502). RESULTS: Our findings indicate statistically
significant differences in the demographic, socioeconomic, and self-perceived
health status tabulations in the MTurk sample relative to the unweighted and
weighted MEPS and BRFSS. The MTurk sample is more likely to be female (65.8% in
MTurk, 50.9% in MEPS, 50.2% in BRFSS), white (80.1% in MTurk, 76.9% in MEPS, and
73.9% in BRFSS), non-Hispanic (91.1%, 82.4%, and 81.4%, respectively), younger,
and less likely to report excellent health status (6.8% in MTurk, 28.3% in MEPS,
and 20.2% in BRFSS). CONCLUSIONS: We find significant differences across
variables that warrant hesitation in using MTurk data as a replacement for the
gold standard datasets in health services research.
PMID- 29329149
TI - Author Response for An Electronic Health Record-based Intervention to Promote
Hepatitis C Virus Testing Among Adults Born Between 1945 and 1965: A Cluster
randomized Trial.
PMID- 29329150
TI - Comparison of Iodine Density Measurement Among Dual-Energy Computed Tomography
Scanners From 3 Vendors.
AB - OBJECTIVES: The aims of this study were to analyze the effect of dual-energy
computed tomography (DECT) scanners and fluid characteristics on iodine
quantification and to calculate the measurement variability range induced by
those variables. METHODS: We performed an experimental phantom study with 4
mediastinal iodine phantoms. Each phantom contained 6 tubes of different iodine
concentrations (0, 1.0, 2.5, 5.0, 10.0, and 20.0 mg/mL) diluted in a specific
solvent, which was water, 10% amino acid solution, 20% lipid emulsion, or 18%
calcium solution, respectively. Mediastinal phantoms were inserted into an
anthropomorphic chest phantom and were scanned with 3 different DECT scanners
from 3 vendors using 2 radiation dosage settings. Iodine density (IoD) and
computed tomography (CT) attenuation at virtual monoenergetic 70-keV images and
virtual nonenhanced images were measured for the iodine phantoms. The effects of
DECT scanners, solvents, and radiation dosage on the absolute measurement error
of IoD and on the CT attenuation profiles were investigated using linear mixed
effects models. Measurement variability range of IoD was also determined.
RESULTS: Absolute error of IoD was not significantly affected by the DECT
systems, kind of solvents, and radiation dosage settings. However, CT attenuation
profiles were significantly different among the DECT vendors and simulated body
fluids. Measurement variability range of IoD was from -0.6 to 0.4 mg/mL for the
true iodine concentration 0 mg/mL. CONCLUSIONS: Dual-energy CT systems and fluid
characteristics did not have a significant effect on the IoD measurement
accuracy. A cutoff of IoD for the determination of a truly enhancing lesion on
DECT would be 0.4 mg/mL.
PMID- 29329152
TI - Remotely Supervised Transcranial Direct Current Stimulation After ECT Improves
Mood and Cognition in a Patient With Multiple Sclerosis: A Case Study.
PMID- 29329153
TI - Limiting Legal Intrusions in ECT Practice, a Commentary on "Regulation of
Electroconvulsive Therapy: A Systematic Review of US State Laws".
PMID- 29329151
TI - Gadolinium Retention, Brain T1 Hyperintensity, and Endogenous Metals: A
Comparative Study of Macrocyclic Versus Linear Gadolinium Chelates in Renally
Sensitized Rats.
AB - OBJECTIVES: This preclinical study was designed to compare gadolinium (Gd) brain
uptake after repeated injections of a macrocyclic Gd-based contrast agent (GBCA)
(gadoterate meglumine) or 2 linear GBCAs (L-GBCAs) (gadobenate dimeglumine or
gadodiamide) on a translational model of moderate renal impairment in rats.
METHODS: The study was carried out in subtotally nephrectomized rats. Animals
received 4 intravenous injections per week of GBCA (gadoterate meglumine,
gadobenate dimeglumine, or gadodiamide) for 5 weeks, resulting in a cumulative
dose of 12 mmol/kg, followed by a 1-month injection-free period. T1
hyperintensity in the deep cerebellar nuclei (DCNs) was investigated, and brain
structures were carefully dissected to determine elemental Gd, iron (Fe), copper
(Cu), and zinc (Zn) distribution by mass spectrometry. Urinary excretion of
endogenous metals was also investigated soon after GBCA administration and
several days later in order to assess a potential transmetalation phenomenon.
RESULTS: Unlike gadoterate, repeated injections of L-GBCAs gadobenate and
gadodiamide both induced T1 hyperintensity in the DCNs. Fine dissection of
cerebral and cerebellar structures demonstrated very low levels or absence of Gd
after repeated injections of gadoterate, in contrast to the two L-GBCAs, for
which the highest total Gd concentration was demonstrated in the DCNs (Gd
concentration in DCNs after 4.5 weeks of injection-free period: 27.1 +/- 6.5
nmol/g for gadodiamide [P < 0.01 vs saline and P < 0.05 vs gadoterate]; 12.0 +/-
2.6 nmol/g for gadobenate [P < 0.09 vs saline]; compared with 1.4 +/- 0.2 nmol/g
for gadoterate [ns vs saline]). The distribution of Gd concentration among the
various brain structures dissected was also well correlated with the Fe
distribution in these structures. No difference in endogenous metal levels in
brain structures was observed. However, injection of gadobenate or gadodiamide
resulted in an increase in urinary Zn excretion (urinary Zn concentrations: 57.9
+/- 20.5 nmol/mL with gadobenate [P < 0.01 vs gadoterate and saline] and 221.6 +/
83.3 nmol/L with gadodiamide [P < 0.0001 vs all other treatments] vs 8.1 +/- 2.3
nmol/L with saline and 10.6 +/- 4.8 nmol/L with gadoterate]). CONCLUSIONS: In a
model of renally impaired rats, only traces of gadoterate meglumine were detected
in the brain with no T1 hyperintensity of the DCNs, whereas marked Gd retention
was observed in almost all brain areas after injections of the L-GBCAs,
gadobenate dimeglumine and gadodiamide. Brain structures with higher Gd uptake
corresponded to those structures containing more Fe. Urinary Zn excretion was
significantly increased after a single injection of L-GBCAs.
PMID- 29329154
TI - Effects on Volume Load and Ratings of Perceived Exertion in Individuals Advanced
Weight-Training After Transcranial Direct Current Stimulation.
AB - The aim of this study was investigate the effects of transcranial direct current
stimulation (tDCS) on volume-load and ratings of perceived exertion. Fifteen
young healthy individuals, aged between 20 and 30 years in advanced strength
training were recruited. Test and retest of the 10 maximum repetitions (10RM)
were performed to determine the reliability of load utilized. Subjects performed
three experimental conditions in a randomized, double-blinded crossover design:
anodic stimulation (a-tDCS), cathodic stimulation (c-tDCS) and sham (2 mA for 20
minutes targeting the dorsolateral prefrontal cortex cortex left). Immediately
after the experimental conditions, subjects completed one set of maximum
repetitions with 10RM load (volume-load) and answered to OMNI-RES (Post
stimulation) (level of significance p <= 0.05). The volume-load showed main
effect for condition (F(2, 28)= 164.801; p<0.001). In post-stimulation, a-tDCS
was greater than c-tDCS (p <= 0.001), and sham (p <= 0.001). For ratings of
perceived exertion (OMNI-RES), the results showed main effect for condition (F(2,
28)=9.768; p <= 0.05). In post-stimulation, c-tDCS was greater than a-tDCS (p <=
0.05), and sham (p <= 0.05). We conclude that the use of a-tDCS may promote
increased in volume-load for the LP45 exercise. Moreover, higher-volume loads are
necessary to maximize muscle strength and anabolism.
PMID- 29329155
TI - Ecological validity and reliability of an age-adapted endurance field test in
young male soccer players.
AB - The purpose of this study was to examine the reliability and the association with
relevant match activities (ecological validity) of an age-adapted field test for
intermittent high-intensity endurance known as Yo-Yo intermittent recovery level
1 children test (YYIR1C) in young male soccer players. Twenty-eight young male
outfield soccer players (age 11.1+/-0.9 years, height 142+/-4.4 cm, body mass
37.0+/-5.9 kg) with at least 2 years of experience in soccer competitions were
tested twice using YYIR1C and an age-adapted competitive small-sided game (i.e.,
9v9), 7 days apart in a random order. The YYIR1C performance showed an excellent
relative (ICC=0.94) and a good absolute reliability (TEM as %CV=5.1%). Very large
and significant associations were found between YYIR1C performance and match high
intensity activity (r=0.53). Large correlations were found between YYIR1C and
match sprinting (r=0.42) and high-intensity metabolic power (r=0.46) distances.
Match total distance was largely associated with YYIR1C (r=0.30). The results of
this study showed that YYIR1C may be considered a valid and reliable field test
for assessing intermittent high-intensity endurance in young male soccer players.
Due to the relevance of aerobic fitness in youth soccer, future studies testing
the sensitiveness of YYIR1C are necessary.
PMID- 29329156
TI - Impact of Integrated Health Care Delivery on Racial and Ethnic Disparities in
Pancreatic Cancer.
AB - OBJECTIVES: The objective of this study was to evaluate whether disparities in
pancreatic cancer diagnosis, treatment, and survival are reduced in an integrated
health system. METHODS: We conducted a retrospective study (2006-2014) among
patients with pancreatic cancer from Kaiser Permanente Southern California.
Racial ethnic groups included non-Hispanic whites (NHW), non-Hispanic blacks
(NHB), Hispanics, and Asians. We used multivariable and Cox regression analyses
to evaluate disparities in diagnosis and treatment utilization (oncology care,
surgery, time to surgery, chemotherapy) and overall survival, respectively.
RESULTS: Among 2103 patients, 54% were diagnosed with stage IV disease, 80%
received oncology consultation, 20% received surgery with mean time to surgery 27
days (standard deviation, 36.8), 50.4% received chemotherapy. Mean overall
survival was 8.6 months (standard deviation, 11.5). There were no differences in
odds of stage IV diagnosis, oncology consultation, surgery, or time to surgery by
racial ethnic group. Asians were more likely to receive chemotherapy (odds ratio,
1.59; 95% confidence interval [CI], 1.09-2.32) compared to NHW. NHB (hazard
ratio, 0.78; 95% CI, 0.67-0.91) and Asians (hazard ratio, 0.81; 95% CI, 0.66
1.00) had improved survival compared to NHW. CONCLUSIONS: Minorities were not
disadvantaged in pancreatic cancer care. Improved health care coordination may
improve current disparities.
PMID- 29329157
TI - Smad4 Loss Correlates With Higher Rates of Local and Distant Failure in
Pancreatic Adenocarcinoma Patients Receiving Adjuvant Chemoradiation.
AB - OBJECTIVES: The tumor suppressor gene SMAD4 (DPC4) is genetically inactivated in
approximately half of pancreatic ductal adenocarcinomas (PDAs). We examined
whether Smad4 tumor status was associated with outcomes after adjuvant
chemoradiation (CRT) for resected PDAs. METHODS: Patients treated with adjuvant
CRT were identified (N = 145). Smad4 status was determined by immunolabeling and
graded as intact or lost. Kaplan-Meier method and multivariable competing risk
analyses were performed. RESULTS: On multivariate competing risk analysis, Smad4
loss was associated with increased risk of local recurrence (LR) (hazard ratio,
2.37; 95% confidence interval, 1.10-5.11; P = 0.027), distant failure (DF)
(hazard ratio, 1.71; 95% confidence interval, 1.03-2.83; P = 0.037), and
synchronous LR and DF at first recurrence (14.9 % vs 5.3%, P = 0.07) compared
with Smad4 intact cancers. Smad4 loss was not associated with median overall
survival (22 vs 22 months; P = 0.63) or disease-free survival (lost [13.6 months]
vs intact [13.5 months], P = 0.79). CONCLUSIONS: After PDA resection and adjuvant
CRT, Smad4 loss correlated with higher risk of LR and DF, but not with survival.
Smad4 loss may help predict which surgical patients are at higher risk for
failure after definitive management and may benefit from intensified adjuvant
therapy.
PMID- 29329158
TI - Expression of Gastrin Family Peptides in Pancreatic Islets and Their Role in beta
Cell Function and Survival.
AB - OBJECTIVES: Modulation of cholecystokinin (CCK) receptors has been shown to
influence pancreatic endocrine function. METHODS: We assessed the impact of the
CCKA and CCKB receptor modulators, (pGlu-Gln)-CCK-8 and gastrin-17, respectively,
on beta-cell secretory function, proliferation and apoptosis and glucose
tolerance, and investigating alterations of CCK and gastrin islet expression in
diabetes. RESULTS: Initially, the presence of CCK and gastrin, and expression of
their receptors were evidenced in beta-cell lines and mouse islets. (pGlu-Gln)
CCK-8 and gastrin-17 stimulated insulin secretion from BRIN-BD11 and 1.1B4 beta
cells, associated with no effect on membrane potential or [Ca]i. Only (pGlu-Gln)
CCK-8 possessed insulin secretory actions in isolated islets. In agreement, (pGlu
Gln)-CCK-8 improved glucose disposal and glucose-induced insulin release in mice.
In addition, (pGlu-Gln)-CCK-8 evoked clear satiety effects. Interestingly, islet
colocalization of CCK with glucagon was elevated in streptozotocin- and
hydrocortisone-induced diabetic mice, whereas gastrin coexpression in alpha cells
was reduced. In contrast, gastrin colocalization within beta-cells was higher in
diabetic mice, while CCK coexpression with insulin was decreased in insulin
deficient mice. (pGlu-Gln)-CCK-8 and gastrin-17 also augmented human and rodent
beta-cell proliferation and offered protection against streptozotocin-induced
beta-cell cytotoxicity. CONCLUSIONS: We highlight the direct involvement of CCKA
and CCKB receptors in pancreatic beta-cell function and survival.
PMID- 29329159
TI - Overexpression of the Long Noncoding RNA HomeoboxA Transcript at the Distal Tip
Predicts Poor Prognosis in a KRAS-Independent Manner in Periampullary Region
Tumors.
AB - OBJECTIVES: Periampullary region tumors (PRTs) are the fifth highest cause of
cancer-related deaths worldwide. Although recent studies have highlighted the
prognostic value of the long noncoding RNA HomeoboxA transcript at the distal tip
(HOTTIP) in patients with pancreatic ductal adenocarcinoma, the relationship
between HOTTIP and clinical outcome of all PRTs remains obscure. The aim of this
study was to clarify the prognostic significance of HOTTIP in patients with all
PRTs related to KRAS mutational status. METHODS: HomeoboxA transcript at the
distal tip expression was detected in 100 PRT samples using quantitative real
time polymerase chain reaction. The associations between HOTTIP levels,
clinicopathological factors, and patient prognosis were also analyzed. RESULTS:
The expression of HOTTIP was found to be significantly upregulated by 32-fold (P
= 0.031) in tumor tissues compared with normal tissues. The over expression of
HOTTIP was related with presence of invasion and metastasis (P = 0.0467, P =
0.0256). In addition, increased HOTTIP expression was associated with poor
prognosis independent of KRAS mutation (P < 0.001; n = 72). Moreover,
multivariate analysis showed that high HOTTIP expression was an unfavorable
prognostic factor for overall survival. CONCLUSIONS: Our findings indicate that
high levels of HOTTIP expression have the potential to be an independent,
unfavorable prognostic factor for patients with PRT.
PMID- 29329160
TI - Predictive Effect of the Total Number of Examined Lymph Nodes on N Staging and
Survival in Pancreatic Neuroendocrine Neoplasms.
AB - OBJECTIVES: We aim to examine the predictive effect of the total number of
examined lymph nodes on N stage and survival in pancreatic neuroendocrine
neoplasms (pNENs) and to determine the optimal threshold. METHODS: A pNENs data
set from 2004 to 2013 was extracted from the Surveillance, Epidemiology, and End
Result database. Multivariate logistic regression and Cox proportional hazards
model were used to identify predictive factors associated with N stage and
survival, respectively. RESULTS: Totally, 1280 pNENs were analyzed. The 11 to 15
lymph nodes examined showed a strong association with the N1 stage (6-10 vs 11
15: odds ratio, 0.672; P = 0.042; 11-15 vs 16-20: odds ratio, 1.049; P = 0.840).
However, it failed to show any survival benefit in pNENs with or without lymph
node metastasis. CONCLUSIONS: Examining at least 11 lymph nodes may be useful to
accurately classify the N stage for pNENs.
PMID- 29329161
TI - Utility of Endoscopic Ultrasonography Screening for Small Pancreatic Cancer and
Proposal for a New Scoring System for Screening.
AB - OBJECTIVES: This study aimed to evaluate the utility of endoscopic
ultrasonography screening for small pancreatic cancer (PC) and propose a new
simple scoring system for selecting individuals who should be screened. METHODS:
Risk factors or symptoms related to PC were tentatively divided into high- and
low-grade risk groups based mainly on reported relative risk values. Numbers of
risk factors were designated as risk scores. Endoscopic ultrasonography screening
was performed for 632 individuals. We analyzed scores for PC detection
prospectively, and risk factors and scores of PC patients retrospectively.
RESULTS: We detected 10 small malignant pancreatic neoplasms (size <=20 mm; 8
PCs; 9 Tis or T1) and 14 advanced PCs. All small PCs and 95.5% of PCs were found
in individuals with low-grade risk scores of at least 3 points (P) or high-grade
risk scores of at least 1P. Both average risk scores were significantly higher in
patients with small PCs (P <= 0.04). Cutoffs for low- and high-grade risk scores
implying the presence of small PC and all PC were 3P and 1P, respectively. When
subjects having one or both cutoff scores were screened, sensitivity and
specificity were 100% and 64.4% for small PCs and 95.5% and 64.4% for all PCs.
CONCLUSION: Endoscopic ultrasonography screening combining new scoring is
effective for detecting small PC.
PMID- 29329162
TI - Reorganizing Care With the Implementation of Electronic Medical Records: A Time
Motion Study in the PICU.
AB - OBJECTIVES: To assess caregivers' patient care time before and after the
implementation of a reorganization of care plan with electronic medical records.
DESIGN: A prospective, observational, time-motion study. SETTING: A level 3 PICU.
PARTICIPANTS: Nurses and orderlies caring for intubated patients during an 8-hour
work shift before (2008-2009) and after (2016) implementation of reorganization
of care in 2013. INTERVENTIONS: The reorganization plan included improved
telecommunication for healthcare workers, increased tasks delegated to orderlies,
and an ICU-specific electronic medical record (Intellispace Critical Care and
Anesthesia information system, Philips Healthcare). MEASUREMENTS AND MAIN
RESULTS: Time spent completing various work tasks was recorded by direct
observation, and proportion of time in tasks was compared for each study period.
A total of 153.7 hours was observed from 22 nurses and 14 orderlies. There was no
significant difference in the proportion of nursing patient care time before
(68.8% [interquartile range, 48-72%]) and after (55% [interquartile range, 51
57%]) (p = 0.11) the reorganization with electronic medical record. Direct
patient care task time for nurses was increased from 27.0% (interquartile range,
30-37%) before to 34.7% (interquartile range, 33-75%) (p = 0.336) after, and
indirect patient care tasks decreased from 33.6% (interquartile range, 23-41%) to
18.6% (interquartile range, 16-22%) (p = 0.036). Documentation time significantly
increased from 14.5% (interquartile range, 12-22%) to 26.2% (interquartile range,
23-28%) (p = 0.032). Nursing productivity ratio improved from 28.3 to 26.0. A
survey revealed that nursing staff was satisfied with the electronic medical
record, although there was a concern for the maintenance of oral communication in
the unit. CONCLUSIONS: The reorganization of care with the implementation of an
ICU-specific electronic medical record in the PICU did not change total patient
care provided but improved nursing productivity, resulting in improved
efficiency. Documentation time was significantly increased, and concern over
reduced oral communication arose, which should be a focus for future electronic
improvement strategies.
PMID- 29329163
TI - The Importance of Parental Connectedness and Relationships With Healthcare
Professionals in End-of-Life Care in the PICU.
AB - OBJECTIVES: Support from healthcare professionals in a PICU is highly valuable
for parents of dying children. The way they care for the patients and their
families affects the parents' initial mourning process. This study explores what
interaction with hospital staff is meaningful to parents in existential distress
when their child is dying in the PICU. DESIGN: Qualitative interview study.
SETTING: Level 3 PICU in the Erasmus University Medical Center-Sophia Children's
Hospital, Rotterdam, and the Netherlands. SUBJECTS: Thirty-six parents of 20
children who had died in this unit 5 years previously. INTERVENTIONS: Parents
participated in audio-recorded interviews in their own homes. The interviews were
transcribed and analyzed using qualitative methods. MEASUREMENTS AND MAIN
RESULTS: Parents' narratives of their child's end-of-life stage in the PICU
bespeak experiences of estrangement, emotional distancing, and loneliness.
Significant moments shared with hospital staff that remained valuable even after
5 years primarily involved personal connectedness, reflected in frequent
informational updates, personal commitment of professionals, and interpersonal
contact with doctors and nurses. CONCLUSIONS: Parents whose children died in the
PICU value personal connectedness to doctors and nurses when coping with
existential distress. Medical and nursing training programs should raise
awareness of parents' need for contact in all interactions but especially in
times of crisis and apprehension.
PMID- 29329164
TI - A Systematic Review of Risk Factors Associated With Cognitive Impairment After
Pediatric Critical Illness.
AB - OBJECTIVES: To identify risk factors associated with cognitive impairment as
assessed by neuropsychologic tests in neurotypical children after critical
illness. DATA SOURCES: For this systematic review, we searched the Cochrane
Library, Scopus, PubMed, Ovid, Embase, and CINAHL databases from January 1960 to
March 2017. STUDY SELECTION: Included were studies with subjects 3-18 years old
at the time of post PICU follow-up evaluation and use of an objective
standardized neuropsychologic test with at least one cognitive functioning
dimension. Excluded were studies featuring patients with a history of cardiac
arrest, traumatic brain injury, or genetic anomalies associated with
neurocognitive impairment. DATA EXTRACTION: Twelve studies met the sampling
criteria and were rated using the Newcastle-Ottawa Quality Assessment Scale. DATA
SYNTHESIS: Ten studies reported significantly lower scores in at least one
cognitive domain as compared to healthy controls or normed population data; seven
of these-four case-control and three prospective cohort studies-reported
significant lower scores in more than one cognitive domain. Risk factors
associated with post critical illness cognitive impairment included younger age
at critical illness and/or older age at follow-up, low socioeconomic status, high
oxygen requirements, and use of mechanical ventilation, sedation, and pain
medications. CONCLUSIONS: Identifying risk factors for poor cognitive outcomes
post critical illness may help healthcare teams modify patient risk and/or
provide follow-up services to improve long-term cognitive outcomes in high-risk
children.
PMID- 29329165
TI - Repeat Rapid Response Events in Children: Characteristics and Outcomes.
AB - OBJECTIVE: We describe the characteristics and outcomes of pediatric repeat rapid
response events within a single hospitalization. We hypothesized that triggers
for repeat rapid response and initial rapid response events are similar, and
repeat rapid response events are associated with high prevalence of medical
complexity and worse outcomes. DESIGN: A 3-year retrospective study. SETTING:
High-volume tertiary academic pediatric hospital. PATIENTS: All rapid response
events were reviewed to identify repeat rapid response events. INTERVENTION:
None. MEASUREMENTS AND MAIN RESULTS: Patient demographics, rapid response
triggers, primary clinical diagnoses, illness acuity scores, medical
interventions, transfers to ICU, occurrence of critical deterioration, and
mortality were reviewed. We reviewed 146 patients with 309 rapid response events
(146 initial rapid response and 163 repeat rapid response: 36% < 24 hr, 38% 24 hr
to 7 d, and 26% > 7 d after initial rapid response). Median age was 3 years, and
60% were males. Eighty-five percentage of repeat rapid response occurred in
medical complexity patients. The triggers for 71% of all repeat rapid response
matched with those of initial rapid response. Transfer to ICU occurred in 69
(47%) of initial rapid response and 124 (76%) of repeat rapid response (p <
0.01). The median hospital stay was 11 and 30 days for previously healthy and
medical complexity patients, respectively (p = 0.16). ICU readmission at repeat
rapid response was associated with longer hospital stay (p < 0.01). Mortality
during hospitalization occurred in 14% (all medically complex) of patients after
repeat rapid response. Hospital mortality after rapid response is 4.4% per our
center's administrative data and 6.7% according to published multicenter data.
CONCLUSIONS: Prevalence of medical complexity was high in patients with repeat
rapid response compared with that reported for pediatric hospitalizations.
Triggers between initial and repeat rapid response events correlated. Transfer to
ICU was more likely after repeat rapid response and among repeat rapid response,
events with ICU readmissions had a longer length of ICU and hospital stay.
Mortality for the repeat rapid response cohort was higher than that for overall
rapid responses in our center and per published reports from other centers.
PMID- 29329166
TI - Hematologic Manifestations of Brucellosis in Children.
AB - BACKGROUND: Brucellosis is a common zoonosis in the Bedouin population of
southern Israel. Limited data exist for the rate and risk factors of hematologic
complication of brucellosis in children. We assessed anemia, leukopenia,
thrombocytopenia and pancytopenia in childhood brucellosis in southern Israel.
METHODS: Our medical center is the sole hospital in southern Israel. All medical
files of brucellosis, 2005-2014, identified through positive blood cultures or
International Classification of Diseases 9th revision coding with positive
serology, were reviewed retrospectively. RESULTS: Overall, 511 brucellosis
episodes were identified; 42% (N = 214) with >=1 cytopenia, including 13% (N =
68) anemia, 28% (N = 144) leukopenia, 14% (N = 74) thrombocytopenia and 2% (N =
9) pancytopenia. Overall, 99.8% of episodes were in Bedouin children and 70% in
males. In 79% of episodes, blood culture was positive for Brucella melitensis.
Acute infections comprised 84% of all episodes. In univariate analysis, older age
(10.49 +/- 4.81 vs. 9.25 +/- 4.89 years), fever (92% vs. 78%), positive blood
culture (84% vs. 75%) and IgM >=1:640 levels (50% vs. 39%) were associated with
cytopenia. In contrast, arthralgia was associated with noncytopenic episodes. In
multivariate analyses, older age (odds ratio = 1.063) and fever (odds ratio =
3.127) were associated with cytopenia. CONCLUSIONS: Brucellosis is commonly
presented with cytopenia, especially in bacteremic episodes with fever. However,
pancytopenia is uncommon and its finding should alert the physician to look for
other possible etiologies.
PMID- 29329167
TI - A Physician's Recommendation for Human Papillomavirus Vaccination: What Makes
African-American Mothers Compliant?
AB - BACKGROUND: Improving human papillomavirus (HPV) vaccination among African
American (AA) female adolescents to reduce the cervical cancer burden is
important and cost-effective. The study objective is to identify factors most
influential to AA mothers' likelihood to comply with a physician's recommendation
to get their daughters the HPV vaccine. METHODS: We conducted a cross-sectional
survey. Participants were recruited through online and community sites (ie,
schools, community centers, etc.) in Alabama. A total of 280 AA mothers and their
adolescent daughters completed the survey. A binary logistic regression was used
to determine factors influencing mother's likelihood to adhere with a physician's
recommendation to get their daughters the HPV vaccine. RESULTS: The most
significant factors influencing mother's likelihood to comply with physician's
recommendation were culture: future-time orientation (P = 0.001), perceived
barriers of HPV vaccination (P = 0.007), perceived susceptibility to HPV (P =
0.047) and perceived benefits of HPV vaccination (P = 0.002). Further exploration
of perceived barriers and perceived benefits found mother's perception that the
HPV vaccine is a good way to protect my daughter's health as the only significant
benefit. No measures of perceived barriers were significant. CONCLUSIONS: A
physician's recommendation should advise AA mothers on the risk of HPV and the
importance of HPV vaccination at an early age to reduce cervical cancer risk. It
should further address mothers' perceived disadvantages of HPV vaccination (eg,
side effects). Incorporating this information in physician recommendation
practices could increase HPV vaccination rates with implications in reducing the
cervical cancer burden among this high-risk population.
PMID- 29329168
TI - Immune Responses to Booster Vaccination With Meningococcal ABCWY Vaccine After
Primary Vaccination With Either Investigational or Licensed Vaccines: A Phase 2
Randomized Study.
AB - BACKGROUND: Current meningococcal prime-boost vaccination schedules include
separate vaccines for serogroups ACWY and B. An investigational combined
serogroups ABCWY vaccine (MenABCWY) was developed to protect against clinically
important Neisseria meningitidis serogroups. METHODS: In this phase 2,
randomized, observer-blind, extension study (NCT01272180), participants 10-25
years of age received 1 booster dose of MenABCWY vaccine at 24 months (M)
postprimary series of MenABCWY (2 doses), 4CMenB (2 doses) or MenACWY-CRM vaccine
(1 dose). Immune responses to booster dose (1M postbooster) and antibody
persistence (24M, 36M postprimary series) were assessed using bactericidal assay
with human complement (hSBA). Reactogenicity and safety were evaluated. RESULTS:
One hundred ninety participants were vaccinated. At 1M after the MenABCWY booster
dose, seroresponse rates against serogroups ACWY ranged between 85% and 96%, 73%
and 100% and 83% and 95% for participants previously receiving MenABCWY, 4CMenB
and MenACWY-CRM, respectively. At 12M postbooster dose, >=67% of participants
across all groups had hSBA titers >=8 for serogroups ACWY, except in 4CMenB
primed individuals for serogroup Y (45%). Across MenABCWY and 4CMenB-primed
groups, hSBA titers >=5 across serogroup B test strains were observed in 82%-100%
and 29%-100% of participants at 1M and 12M postbooster, respectively. Geometric
mean titers against serogroups ACWY increased from pre- to 1M postboosting with
MenABCWY and persisted at 12M. The reactogenicity and safety profile of MenABCWY
was similar to that of 4CMenB. CONCLUSIONS: MenABCWY may be suitable for prime
boost schedules against meningococcal disease, including regimens involving a
primary series of either 4CMenB or MenACWY-CRM licensed vaccines.
PMID- 29329169
TI - Differences in Immunization Site Pain in Toddlers Vaccinated With Either the 10-
or the 13-Valent Pneumococcal Conjugate Vaccine.
AB - BACKGROUND: Immunization site pain is a common and unpleasant experience for both
children and adults. It is a source of anxiety and distress and may ultimately
result in nonadherence to vaccination schedules. There is limited information on
how different brands of vaccines affect the intensity of immediate pain at the
time of vaccine injection. METHODS: Children in the United Kingdom (n = 178) were
randomized to receive a booster dose of either the 10- or the 13-valent
pneumococcal conjugate vaccine (PCV-10 or PCV-13). Immediate immunization site
pain was assessed using validated pain assessment tools and crying time to
investigate factors that may interfere with parental compliance to vaccination.
RESULTS: Pain measurements were available for n >= 74 and n >= 78 PCV-10 and PCV
13 recipients, respectively. PCV-13 recipients had significantly higher scores on
the observer-rated modified behavioral pain scale than did those receiving PCV
10. No significant differences in the induction of pain between the 2 vaccines
were found when a parent-rated pain assessment tool or crying time was used.
CONCLUSIONS: PCV-10 administration was associated with slightly less acute pain
compared with the injection of PCV-13, but the size of the difference was small
and is of unknown clinical significance.
PMID- 29329170
TI - What's New in Shock, February 2018?
PMID- 29329171
TI - Nonhuman Primate (Rhesus Macaque) Models of Severe Pressure-Targeted Hemorrhagic
and Polytraumatic Hemorrhagic Shock.
AB - BACKGROUND: We endeavored to develop clinically translatable nonhuman primate
(NHP) models of severe polytraumatic hemorrhagic shock. METHODS: NHPs were
randomized into five severe pressure-targeted hemorrhagic shock (PTHS) +/-
additional injuries scenarios: 30-min PTHS (PTHS-30), 60-min PTHS (PTHS-60), PTHS
60 + soft tissue injury (PTHS-60+ST), PTHS-60+ST + femur fracture (PTHS
60+ST+FF), and decompensated PTHS+ST+FF (PTHS-D). Physiologic parameters were
recorded and blood samples collected at five time points with animal observation
through T = 24 h. Results presented as mean +/- SEM; statistics: log
transformation followed by two-way ANOVA with Bonferroni multiple comparisons,
Wilcoxon nonparametric test for comparisons, and the Friedmans' one-way ANOVA;
significance: P < 0.05. RESULTS: Percent blood loss was 40% +/- 2, 59% +/- 3, 52%
+/- 3, 49% +/- 2, and 54% +/- 2 for PTHS-30, PTHS-60, PTHS-60+ST, PTHS-60+ST+FF,
and PTHS-D, respectively. All animals survived to T = 24 h except one in each of
the PTHS-60 and PTHS-60+ST+FF groups and seven in the PTHS-D group. Physiologic,
coagulation, and inflammatory parameters demonstrated increasing derangements
with increasing model severity. CONCLUSION: NHPs exhibit a high degree of
resilience to hemorrhagic shock and polytrauma as evidenced by moderate
perturbations in metabolic, coagulation, and immunologic outcomes with up to 60
min of profound hypotension regardless of injury pattern. Extending the duration
of PTHS to the point of decompensation in combination with polytraumatic injury,
evoked derangements consistent with those observed in severely injured trauma
patients which would require ICU care. Thus, we have successfully established a
clinically translatable NHP trauma model for use in testing therapeutic
interventions to trauma.
PMID- 29329172
TI - Clinical Features and Outcomes of Post-Traumatic Silent Sinus Syndrome.
AB - PURPOSE: To identify demographic features and clinical outcomes associated with
post-traumatic silent sinus syndrome. METHODS: A retrospective review was carried
out at 3 academic medical centers to identify all cases of post-traumatic silent
sinus syndrome. Clinical features and management strategies were recorded.
Postoperative outcomes were assessed, and statistical analyses were performed via
a dedicated computerized software package. RESULTS: Twenty cases were identified
(14 men and 6 women, mean age = 44.2 years). Seven patients underwent sinus
surgery as the sole means of treatment, and the mean pre- and postoperative
enophthalmos measurements were 2.86 and 1.93 mm. Alternatively, 13 patients
underwent combined orbital reconstruction and sinus surgery, respectively; the
mean pre- and postoperative enophthalmos measurements were 3.42 and 0.39 mm,
respectively. The change in enophthalmos was statistically significantly greater
in patients who underwent sinus surgery and orbital reconstruction (p = 0.00028).
Among patients who underwent sinus surgery alone, one patients (14.2%)
experienced complete resolution of enophthalmos, as compared with 10 patients
(76.9%) who underwent combined procedures. CONCLUSIONS: This study represents the
largest published cohort of patients with post-traumatic silent sinus syndrome.
Combined orbital reconstruction and sinus surgery results in greater reductions
of enophthalmos and a markedly improved chance of postoperative symmetry of globe
position.
PMID- 29329173
TI - Continuous Positive Airway Pressure Thresholds for Nasolacrimal Air Regurgitation
in a Cadaveric Model.
AB - PURPOSE: To elucidate the mechanisms underlying nasolacrimal air regurgitation
(AR) in the setting of continuous positive airway pressure therapy. METHODS:
Twelve nasolacrimal systems of 6 fresh female human cadavers were evaluated
individually for AR using continuous positive airway pressure therapy before any
nasolacrimal procedure. Cadavers were then randomly assigned to undergo
nasolacrimal duct probing or endoscopic dacryocystorhinostomy and then each
hemisystem was again evaluated for AR. The pressure where AR was first observed
(discovery pressure) or maximum possible pressure in systems without AR was
recorded. In systems that demonstrated AR, the pressure was then gradually
decreased to the lowest pressure where regurgitation persisted. This pressure was
recorded as the secondary threshold pressure. RESULTS: None of the 12 unoperated
nasolacrimal systems or the 6 systems that underwent nasolacrimal duct probing
demonstrated AR through the maximum continuous positive airway pressure therapy
(30 cm H2O). After endoscopic dacryocystorhinostomy, all 6 nasolacrimal systems
demonstrated AR. The mean discovery pressure was 16.0 cm H2O (range, 14.0-18.0 cm
H2O) and mean secondary threshold pressure was 7.25 cm H2O (range, 6.5-8.0 cm
H2O). CONCLUSIONS: Air regurgitation during continuous positive airway pressure
therapy in the setting of prior endoscopic dacryocystorhinostomy can be
replicated in a cadaver model. The secondary threshold pressures required for AR
in this model were similar to AR pressures reported clinically. Prior to
dacryocystorhinostomy, patients using continuous positive airway pressure therapy
should be counseled on AR, and physicians should consider this phenomenon when
evaluating ophthalmic complaints in postoperative patients on positive airway
pressure therapy.
PMID- 29329174
TI - Symmetry of Upper Eyelid Contour After Unilateral Blepharoptosis Repair With a
Single-strip Frontalis Suspension Technique.
AB - PURPOSE: To analyze the upper eyelid contour of patients with unilateral
congenital ptosis who underwent single-strip frontalis suspension. METHODS: The
authors compared the upper eyelid shape of the right and left eyes of 10 patients
who underwent unilateral frontalis suspension with a single strip of autogenous
fascia. At a mean postoperative time of 10.1 +/- 4.01 months, the image J
software was used to measure the ratio between the nasal and temporal areas of
the upper half of the palpebral fissure. The midpupil upper eyelid distance
(MRD1) was also measured on the photos with the same software. The nonparametric
Wilcoxon signed-rank test was used to compare the data. RESULTS: Postoperative
MRD1 ranged from 2.5 to 4.7 mm (median = 3.8) on the affected side. The MRD1 for
nonoperated eyelid ranged from 1.8 to 5.0 mm (median = 3.5). On the operated
side, the temporal areas ranged from 50.3 to 85.7 mm (median 65.2) and nasal
areas ranged from 41.5 to 72.3 (the median was 60.1). In the contralateral,
nonoperated palpebral fissures, the temporal areas ranged from 42.7 to 94.3 mm
(median = 54.5) and the nasal areas ranged from 36.8 to 86.1 mm (median 52.3).
The T/N ratio distributions were almost identical between groups, ranging from
0.9 to 1.2 (median = 1.1) in the operated eyes and from 0.9 to 1.3 (median = 1.1)
in the fellow eyes. CONCLUSIONS: In autogenous fascia frontalis suspension
procedures, the upper eyelid contour of the ptotic eyelids can be adequately
normalized with a single area of traction on the tarsal plate.
PMID- 29329176
TI - A Cost Analysis of Gyrase A Testing and Targeted Ciprofloxacin Therapy Versus
Recommended 2-Drug Therapy for Neisseria gonorrhoeae Infection.
AB - BACKGROUND: Novel approaches to combating drug-resistant Neisseria gonorrhoeae
infections are urgently needed. Targeted therapy with ciprofloxacin has been made
possible by a rapid assay for genotyping the gyrase A (gyrA) gene; a nonmutated
gene reliably predicts susceptibility to ciprofloxacin. METHODS: We determined
the costs of running the gyrA assay, 500 mg of ciprofloxacin, 250 mg of
ceftriaxone injection, and 1000 mg of azithromycin. Cost estimates for gyrA
testing included assay reagents and labor. Cost estimates for ceftriaxone
included medication, injection, administration, supplies, and equipment. We
measured the cost of using the gyrA assay and treatment based on genotype using
previously collected data over a 13-month period between November 2015 and
November 2016 for all N. gonorrhoeae cases diagnosed at UCLA. We subsequently
developed 3 cost models, varying the frequency of testing and prevalence of N.
gonorrhoeae infections with ciprofloxacin-resistant or genotype-indeterminate
results. We compared those estimates with the cost of recommended 2-drug therapy
(ceftriaxone and azithromycin). RESULTS: Based on a 65.3% prevalence of cases
with ciprofloxacin-resistant or genotype indeterminate N. gonorrhoeae infections
when running an average of 1.7 tests per day, the per-case cost of gyrA
genotyping and targeted therapy was US $197.19. The per-case cost was US $155.16
assuming a 52.6% prevalence of ciprofloxacin-resistant or genotype-indeterminate
infections when running an average of 17 tests per day. The per-case cost of 2
drug therapy was US $142.75. CONCLUSIONS: Direct costs of gyrA genotyping and
targeted ciprofloxacin therapy depend on the prevalence of ciprofloxacin
resistant or genotype-indeterminate infections and testing frequency.
PMID- 29329177
TI - A Comparison of Real-Time Polymerase Chain Reaction Assays for the Detection of
Antimicrobial Resistance Markers and Sequence Typing From Clinical Nucleic Acid
Amplification Test Samples and Matched Neisseria gonorrhoeae Culture.
AB - Real-time polymerase chain reaction (PCR) assays to detect antimicrobial
resistance-associated mutations were tested on Neisseria gonorrhoeae-positive
clinical samples with matched isolates. Of the nucleic acid amplification
tests/cultures, 87.7% (64/73), 98.6% (72/73), and 98.4% (62/63) predicted
cephalosporin, ciprofloxacin, and azithromycin susceptibilities, respectively. N.
gonorrhoeae multiantigen sequence type was correctly predicted for 98.7% (79/80),
and 13 of 58 N. gonorrhoeae-negative specimens showed false-positive results.
PMID- 29329178
TI - Chlamydia and Gonorrhea Acquisition Among Adolescents and Young Adults in
Pennsylvania: A Rural and Urban Comparison.
AB - Adolescent and young adult chlamydia and gonorrhea rates in rural versus urban
communities of Pennsylvania were analyzed from 2004 to 2014. Higher rates of
chlamydia and gonorrhea have been documented in rural youth, making them more
likely to acquire to suffer adverse outcomes than youth in urban populations.
PMID- 29329175
TI - Clinical Description, Molecular Analysis of TWIST2 Gene, and Surgical Treatment
in a Patient With Barber-Say Syndrome.
AB - Barber-Say syndrome is a rare autosomal dominant disease characterized by
dysmorphic features, mainly of the eyelids and skin. It is caused by heterozygous
mutations in gene TWIST2, localized in chromosome 2q37.3. The authors present the
case of a pediatric patient with a clinical diagnosis of Barber-Say syndrome with
ocular symptoms related to exposure keratitis. Molecular analysis of her DNA
revealed a mutation on TWIST2 gene confirming the diagnosis of Barber-Say
syndrome. Surgical treatment of the patient's eyelids resolved her signs and
symptoms.
PMID- 29329179
TI - Should Asymptomatic Men Who Have Sex With Men Be Screened for Oropharyngeal
Chlamydia? Clinical Outcomes From a Cross-Sectional Study.
AB - OBJECTIVE: To help inform screening guidelines, we estimated the proportion of
asymptomatic men who have sex with men (MSM) with oropharyngeal chlamydia. STUDY
DESIGN: An audit of asymptomatic MSM attending a sexual health service from March
2015 to April 2016 was conducted. They each had an oropharyngeal swab that was
tested for Chlamydia trachomatis by transcription-mediated nucleic acid
amplification. In addition, a random sample of 17 swabs that initially tested
positive had confirmatory testing to determine the likelihood of true positivity.
RESULTS: We collected 4877 oropharyngeal swabs: 72 (1.5%; 95% confidence interval
[CI], 1.2-1.9) were diagnosed positive for chlamydia. Most (n = 56 [78%]; 95% CI,
67-86) only had oropharyngeal chlamydia detected (i.e., no concurrent
extraoropharyngeal chlamydia and/or gonorrhea). Of the 17 samples that underwent
confirmation, all confirmed positive (100%; 95% CI, 82-100). CONCLUSIONS:
Although oropharyngeal chlamydia prevalence was low among asymptomatic MSM, most
oropharyngeal chlamydia cases had no chlamydia at other sites, and these cases
would have been missed and not treated if routine oropharyngeal chlamydia testing
was not done.
PMID- 29329180
TI - Diplopia: An Overlooked Feature in Patients With Neurosyphilis. Report of 2 Cases
and Literature Review.
AB - Both neurosyphilis and diplopia are widely known medical terms. Nevertheless, low
clinical awareness by the physician and the often-overlooked presentation of
diplopia, make the combination of neurosyphilis and diplopia rarely observed. In
this article, we report 2 neurosyphilitic patients presenting with diplopia and
review 8 additional case reports of neurosyphilis with diplopia, with a total of
10 cases to be analyzed.
PMID- 29329181
TI - What Is the Optimal Time to Retest Patients With a Urogenital Chlamydia
Infection? A Randomized Controlled Trial.
AB - BACKGROUND: Chlamydia trachomatis is a common, often recurring sexually
transmitted infection, with serious adverse outcomes in women. Current guidelines
recommend retesting after a chlamydia infection, but the optimum timing is
unknown. We assessed the optimal retest interval after urogenital chlamydia
treatment. METHODS: A randomized controlled trial among urogenital chlamydia
nucleic acid amplification test positive heterosexual clients of the Amsterdam
sexually transmitted infection clinic. After treatment, patients were randomly
assigned for retesting 8, 16, or 26 weeks later. Patients could choose to do this
at home (and send a self-collected sample by mail) or at the clinic. Retest
uptake and chlamydia positivity at follow-up were calculated. RESULTS: Between
May 2012 and March 2013, 2253 patients were included (45% men; median age, 23
years; interquartile range, 21-26). The overall uptake proportion within 35 weeks
after the initial visit was significantly higher in the 8-week group (77%)
compared with the 16- and 26-week groups (67% and 64%, respectively, P < 0.001),
and the positivity proportions among those retested were comparable (P = 0.169).
The proportion of people with a diagnosed recurrent chlamydia infection among all
randomized was similar between the groups (n = 69 [8.6%], n = 52 [7.4%], and n =
69 [9.3%]; P = 0.4). CONCLUSIONS: Patients with a recent urogenital chlamydia are
at high risk of recurrence of chlamydia and retesting them is an effective way of
detecting chlamydia cases. We recommend inviting patients for a re-test 8 weeks
after the initial diagnosis and treatment.
PMID- 29329182
TI - Rapid Increase in Gonorrhea Cases With Reduced Susceptibility to Azithromycin in
Columbus, Ohio.
PMID- 29329183
TI - Hepatitis E Virus Infection in Kidney Transplant Patients: A Single-Center Study.
PMID- 29329184
TI - Listening to Living Donors.
PMID- 29329186
TI - High-Sensitivity Troponins in Liver Transplantation: How Will They Change Our
Practice?
PMID- 29329185
TI - Vasodilation During Normothermic Machine Perfusion; Preventing the No-Reflow
Phenomena.
PMID- 29329187
TI - Deceased Donor Organ Transplantation Performed in the United States for
Noncitizens and Nonresidents.
AB - Since 2012, the Organ Procurement and Transplantation Network (OPTN)/United
Network for Organ Sharing (UNOS) has required transplant centers to record the
citizenship residency status of patients undergoing transplantation in the United
States. This policy replaced the 5% threshold of the non-US citizen/nonresidents
(NC/NR) undergoing organ transplantation that could result in an audit of
transplant center activity. Since April 1, 2015, the country of residence for the
NC/NR on the waitlist has also been recorded. We analyzed the frequency of NC/NR
deceased donor organ transplants and waitlist registrations at all US transplant
centers by data provided by UNOS for that purpose to the UNOS Ad Hoc
International Relations Committee. During the period of 2013 to 2016, 1176
deceased donor transplants (of all organs) were performed in non-US citizen/non
US resident (NC/NR) candidates (0.54% of the total number of transplants). We
focused on high-volume NC/NR transplant centers that performed more than 5% of
the deceased donor kidney or liver transplants in NC/NR or whose waitlist
registrants exceeded 5% NC/NR. This report was prepared to fulfill the
transparency policy of UNOS to assure a public trust in the distribution of
organs. When viewed with a public awareness of deceased donor organ shortages, it
suggests the need for a more comprehensive understanding of current NC/NR
activity in the United States. Patterns of organ specific NC/NR registrations and
transplantations at high-volume centers should prompt a review of transplant
center practices to determine whether the deceased donor and center resources may
be compromised for their US patients.
PMID- 29329188
TI - The Impact of Combined Warm Ischemia Time on Development of Acute Kidney Injury
in Donation After Circulatory Death Liver Transplantation: Stay Within the Golden
Hour.
AB - BACKGROUND: Acute kidney injury (AKI) is a common complication after liver
transplantation and more frequently observed when high-risk grafts, such as
donation after circulatory death (DCD) grafts are used. Our aim was to
investigate the impact of the ischemia periods on development of AKI in DCD liver
transplantation. METHODS: We performed a 2-center retrospective study with 368
DCD graft-recipients. Donor warm ischemia time (DWIT) was divided into agonal
phase (withdrawal of life support-cardiac arrest) and asystolic phase (cardiac
arrest-start cold perfusion). We introduced a new period of warm ischemia: the
combined warm ischemia time (combined WIT), which was defined as the sum of DWIT
and recipient WIT. RESULTS: AKI was observed in 65% of the recipients and severe
AKI in 41% (KDIGO stage 2/3). The length of combined WIT increased significantly
with AKI severity: 61 minutes in recipients without AKI up to 69 minutes in
recipients with the most severe form of AKI (P < 0.001). On multivariable
analysis, increasing duration of the combined WIT was associated with an
increased risk of developing severe AKI (odds ratio, 1.032 per every extra
minute; 95% confidence interval, 1.014-1.051; P < 0.001). No relation was
observed between length of cold ischemia time and severe AKI. CONCLUSIONS:
Combined WIT is a newly defined period of warm ischemia in DCD liver
transplantation. Length of combined WIT is associated with severity of
postoperative AKI and should ideally not exceed 60 minutes.
PMID- 29329189
TI - Beta Cell Death by Cell-free DNA and Outcome After Clinical Islet
Transplantation.
AB - BACKGROUND: Optimizing engraftment and early survival after clinical islet
transplantation is critical to long-term function, but there are no reliable,
quantifiable measures to assess beta cell death. Circulating cell-free DNA
(cfDNA) derived from beta cells has been identified as a novel biomarker to
detect cell loss and was recently validated in new-onset type 1 diabetes and in
islet transplant patients. METHODS: Herein we report beta cell cfDNA measurements
after allotransplantation in 37 subjects and the correlation with clinical
outcomes. RESULTS: A distinctive peak of cfDNA was observed 1 hour after
transplantation in 31 (83.8%) of 37 subjects. The presence and magnitude of this
signal did not correlate with transplant outcome. The 1-hour signal represents
dead beta cells carried over into the recipient after islet isolation and
culture, combined with acute cell death post infusion. Beta cell cfDNA was also
detected 24 hours posttransplant (8/37 subjects, 21.6%). This signal was
associated with higher 1-month insulin requirements (P = 0.04), lower 1-month
stimulated C-peptide levels (P = 0.01), and overall worse 3-month engraftment, by
insulin independence (receiver operating characteristic-area under the curve =
0.70, P = 0.03) and beta 2 score (receiver operating characteristic-area under
the curve = 0.77, P = 0.006). CONCLUSIONS: cfDNA-based estimation of beta cell
death 24 hours after islet allotransplantation correlates with clinical outcome
and could predict early engraftment.
PMID- 29329191
TI - Income Disparities in the Prevalence, Severity, and Costs of Co-occurring Chronic
and Behavioral Health Conditions.
AB - BACKGROUND: Behavioral health problems usually co-occur along with physical
health problems, resulting in higher health care costs. These co-occurring
conditions are likely to be more prevalent and serious among low income patients,
affecting both the quality and costs of care. OBJECTIVE: To examine the
prevalence, severity, and health care costs of co-occurring chronic and
behavioral health conditions among low income people compared with higher income
people. METHODS: Analysis of the 2011-2014 Medical Expenditure Panel Survey.
Sample includes 146,000 persons aged 18-64 years. Regression analysis was used to
examine how the combination of behavioral health conditions and chronic health
conditions is associated with health care expenditures, and how this association
differs by family income. RESULTS: (1) Comorbid behavioral health problems are
more prevalent and serious among low income people with chronic conditions
compared with higher income people; (2) among patients with co-occurring chronic
and behavioral problems, average annual spending is greater among the low income
patients ($9472) compared with high income patients ($7457); (3) higher costs
among low income patients with co-occurring conditions reflects their poorer
mental and physical health, relative to higher income patients. CONCLUSIONS: For
many low income people, comorbid behavioral problems need to be understood in the
social context in which they live. Simply screening low income people for
behavioral health problems may not be sufficient unless there is greater
understanding of the mechanisms that both cause and exacerbate chronic and
behavioral health problems in the low income population.
PMID- 29329193
TI - Mustn1: A Developmentally Regulated Pan-Musculoskeletal Cell Marker and
Regulatory Gene.
AB - The Mustn1 gene encodes a small nuclear protein (~9.6 kDa) that does not belong
to any known family. Its genomic organization consists of three exons
interspersed by two introns and it is highly homologous across vertebrate
species. Promoter analyses revealed that its expression is regulated by the AP
family of transcription factors, especially c-Fos, Fra-2 and JunD. Mustn1 is
predominantly expressed in the major tissues of the musculoskeletal system: bone,
cartilage, skeletal muscle and tendon. Its expression has been associated with
normal embryonic development, postnatal growth, exercise, and regeneration of
bone and skeletal muscle. Moreover, its expression has also been detected in
various musculoskeletal pathologies, including arthritis, Duchenne muscular
dystrophy, other skeletal muscle myopathies, clubfoot and diabetes associated
muscle pathology. In vitro and in vivo functional perturbation revealed that
Mustn1 is a key regulatory molecule in myogenic and chondrogenic lineages. This
comprehensive review summarizes our current knowledge of Mustn1 and proposes that
it is a new developmentally regulated pan-musculoskeletal marker as well as a key
regulatory protein for cell differentiation and tissue growth.
PMID- 29329195
TI - Dietary Antioxidants and Health Promotion.
AB - Accumulating scientific evidence suggests that over-production of reactive oxygen
species (ROS) may be the root cause of chronic diseases such as cancer,
cardiovascular diseases, neurodegeneration, and ageing per se [1,2].[...].
PMID- 29329196
TI - Is the Skin Absorption of Hydrocortisone Modified by the Variability in Dosing
Topical Products?
AB - Fingertip units have been proposed as a tool to standardize topical therapy with
semisolid formulations. However, no studies to date have characterized the
variability in dosing by patients using this concept and whether this variability
ultimately affects the topical absorption of drugs. This work aimed to answer
these two questions. A first study determined the dose measured, the area of
spread and the area-normalized dose for a 1% hydrocortisone cream and ointment
applied by members of the public using this dosing approach before and after
brief counselling. Then, in vivo tape-stripping and in vitro permeation studies
investigated whether the variability in the area-normalized dose altered the skin
absorption of hydrocortisone. Participants applied greater doses and spread them
over larger areas after a short counselling intervention leading to smaller area
normalized doses. In vivo hydrocortisone uptake by the stratum corneum was
significantly greater for the higher normalized dose and the differences were
further supported by the in vitro permeation studies. However, these differences
were relatively small and not proportional to the increase in normalized dose.
This work shows that, following brief advice, patients and carers can apply
consistent and sufficient doses of corticosteroids whilst minimizing risks and
variability in hydrocortisone absorption.
PMID- 29329197
TI - Long-Term Functional Outcome of Surgical Treatment for Thoracic Outlet Syndrome.
AB - First rib resection for thoracic outlet syndrome (TOS) is clinically successful
and safe in most patients. However, long-term functional outcomes are still
insufficiently known. Long-term functional outcome was assessed using a validated
questionnaire. A multicenter retrospective cohort study including all patients
who underwent operations for TOS from January 2005 until December 2016. Clinical
records were reviewed and the long-term functional outcome was assessed by the 11
item version of the Disability of the Arm, Shoulder, and Hand (QuickDASH)
questionnaire. Sixty-two cases of TOS in 56 patients were analyzed: 36 neurogenic
TOS, 13 arterial TOS, 7 venous TOS, and 6 combined TOS. There was no 30-day
mortality. One reoperation because of bleeding was performed and five patients
developed a pneumothorax. Survey response was 73% (n = 41) with a follow-up
ranging from 1 to 11 years. Complete relief of symptoms was reported
postoperatively in 27 patients (54%), symptoms improved in 90%, and the mean
QuickDASH score was 22 (range, 0-86). Long-term functional outcome of surgical
treatment of TOS was satisfactory, and surgery was beneficial in 90% of patients,
with a low risk of severe morbidity. However, the mean QuickDASH scores remain
higher compared with the general population, suggesting some sustained functional
impairment despite clinical improvement of symptoms.
PMID- 29329199
TI - Pressure Induced Densification and Compression in a Reprocessed Borosilicate
Glass.
AB - Pressure induced densification and compression of a reprocessed sample of
borosilicate glass has been studied by X-ray radiography and energy dispersive X
ray diffraction using a Paris-Edinburgh (PE) press at a synchrotron X-ray source.
The reprocessing of a commercial borosilicate glass was carried out by cyclical
melting and cooling. Gold foil pressure markers were used to obtain the sample
pressure by X-ray diffraction using its known equation of state, while X-ray
radiography provided a direct measure of the sample volume at high pressure. The
X-ray radiography method for volume measurements at high pressures was validated
for a known sample of pure alpha-Iron to 6.3 GPa. A sample of reprocessed
borosilicate glass was compressed to 11.4 GPa using the PE cell, and the
flotation density of pressure recovered sample was measured to be 2.755 gm/cc,
showing an increase in density of 24%, as compared to the starting sample. The
initial compression of the reprocessed borosilicate glass measured by X-ray
radiography resulted in a bulk modulus of 30.3 GPa in good agreement with the
32.9 GPa value derived from the known elastic constants. This method can be
applied to variety of amorphous materials under high pressures.
PMID- 29329201
TI - Population Reference Values for Serum Methylmalonic Acid Concentrations and Its
Relationship with Age, Sex, Race-Ethnicity, Supplement Use, Kidney Function and
Serum Vitamin B12 in the Post-Folic Acid Fortification Period.
AB - Serum methylmalonic acid (MMA) is elevated in vitamin B-12 deficiency and in
kidney dysfunction. Population reference values for serum MMA concentrations in
post-folic acid fortification period are lacking. Aims of this study were to
report the population reference values for serum MMA and to evaluate the relation
between serum MMA and sex, age, race-ethnicity, kidney dysfunction and vitamin B
12. We used data from three National Health and Nutrition Examination Surveys,
1999-2000, 2001-2002 and 2003-2004 conducted after folic acid fortification
commenced (n = 18,569). Geometric mean MMA was ~22.3% higher in non-Hispanic
white compared to non-Hispanic black (141.2 vs. 115.5 nmol/L) and was ~62.7%
higher in >70 years old persons compared to 21-30 years old persons (196.9 vs.
121.0 nmol/L). Median serum MMA was ~28.5% higher in the 1st the quartile of
serum vitamin B-12 than in the 4th quartile of serum vitamin B-12 and was ~35.8%
higher in the 4th quartile of serum creatinine than in the 1st quartile of serum
creatinine. Multivariate-adjusted serum MMA concentration was significantly
associated with race-ethnicity (p < 0.001) and age (p < 0.001) but not with sex
(p = 0.057). In this large US population based study, serum MMA concentrations
presented here reflect the post-folic acid fortification scenario. Serum MMA
concentrations begin to rise at the age of 18-20 years and continue to rise
afterwards. Age-related increase in serum MMA concentration is likely to be due
to a concomitant decline in kidney function and vitamin B-12 status.
PMID- 29329203
TI - Thermoelectric Mixed Thick-/Thin Film Microgenerators Based on Constantan/Silver.
AB - This paper describes the design, manufacturing and characterization of newly
developed mixed thick-/thin film thermoelectric microgenerators based on
magnetron sputtered constantan (copper-nickel alloy) and screen-printed silver
layers. The thermoelectric microgenerator consists of sixteen thermocouples made
on a 34.2 * 27.5 * 0.25 mm3 alumina substrate. One of thermocouple arms was made
of magnetron-sputtered constantan (Cu-Ni alloy), the second was a Ag-based screen
printed film. The length of each thermocouple arm was equal to 27 mm, and their
width 0.3 mm. The distance between the arms was equal to 0.3 mm. In the first
step, a pattern mask with thermocouples was designed and fabricated. Then, a
constantan layer was magnetron sputtered over the whole substrate, and a
photolithography process was used to prepare the first thermocouple arms. The
second arms were screen-printed onto the substrate using a low-temperature silver
paste (Heraeus C8829A or ElectroScience Laboratories ESL 599-E). To avoid
oxidation of constantan, they were fired in a belt furnace in a nitrogen
atmosphere at 550/450 degrees C peak firing temperature. Thermoelectric and
electrical measurements were performed using the self-made measuring system. Two
pyrometers included into the system were used for temperature measurement of hot
and cold junctions. The estimated Seebeck coefficient, alpha was from the range
35 - 41 uV/K, whereas the total internal resistances R were between 250 and 3200
ohms, depending on magnetron sputtering time and kind of silver ink (the
resistance of a single thermocouple was between 15.5 and 200 ohms).
PMID- 29329205
TI - Improving Odometric Accuracy for an Autonomous Electric Cart.
AB - In this paper, a study of the odometric system for the autonomous cart Verdino,
which is an electric vehicle based on a golf cart, is presented. A mathematical
model of the odometric system is derived from cart movement equations, and is
used to compute the vehicle position and orientation. The inputs of the system
are the odometry encoders, and the model uses the wheels diameter and distance
between wheels as parameters. With this model, a least square minimization is
made in order to get the nominal best parameters. This model is updated,
including a real time wheel diameter measurement improving the accuracy of the
results. A neural network model is used in order to learn the odometric model
from data. Tests are made using this neural network in several configurations and
the results are compared to the mathematical model, showing that the neural
network can outperform the first proposed model.
PMID- 29329202
TI - EpCAM Immunotherapy versus Specific Targeted Delivery of Drugs.
AB - The epithelial cell adhesion molecule (EpCAM), or CD326, was one of the first
cancer associated biomarkers to be discovered. In the last forty years, this
biomarker has been investigated for use in personalized cancer therapy, with the
first monoclonal antibody, edrecolomab, being trialled in humans more than thirty
years ago. Since then, several other monoclonal antibodies have been raised to
EpCAM and tested in clinical trials. However, while monoclonal antibody therapy
has been investigated against EpCAM for almost 40 years as primary or adjuvant
therapy, it has not shown as much promise as initially heralded. In this review,
we look at the reasons why and consider alternative targeting options, such as
aptamers, to turn this almost ubiquitously expressed epithelial cancer biomarker
into a viable target for future personalized therapy.
PMID- 29329204
TI - Lipid-Lowering Polyketides from the Fungus Penicillium Steckii HDN13-279.
AB - Seven new polyketides, named tanzawaic acids R-X (1-6, 11), along with seven
known analogues (7-10 and 12-14), were isolated from Penicillium steckii HDN13
279. Their structures, including the absolute configurations, were elucidated by
NMR, MS, X-ray diffraction, circular dichroism (CD) analyses and chemical
derivatization. Five compounds (2, 3, 6, 10 and 12) significantly decreased the
oleic acid (OA)-elicited lipid accumulation in HepG2 liver cells at the
concentration of 10 MUM, among which, four compounds (3, 6, 10 and 12)
significantly decreased intracellular total cholesterol (TC) levels and three
Compounds (3, 6, and 10) significantly decreased intracellular triglyceride (TG)
levels. Moreover, the TG-lowering capacities of compounds 6 and 10 were
comparable with those of simvastatin, with the TG levels being nearly equal to
blank control. This is the first report on the lipid-lowering activity of
tanzawaic acid derivatives.
PMID- 29329206
TI - Preparation of Cu2O-Reduced Graphene Nanocomposite Modified Electrodes towards
Ultrasensitive Dopamine Detection.
AB - Cu2O-reduced graphene oxide nanocomposite (Cu2O-RGO) was used to modify glassy
carbon electrodes (GCE), and applied for the determination of dopamine (DA). The
microstructure of Cu2O-RGO nanocomposite material was characterized by scanning
electron microscope. Then the electrochemical reduction condition for preparing
Cu2O-RGO/GCE and experimental conditions for determining DA were further
optimized. The electrochemical behaviors of DA on the bare electrode, RGO- and
Cu2O-RGO-modified electrodes were also investigated using cyclic voltammetry in
phosphate-buffered saline solution (PBS, pH 3.5). The results show that the
oxidation peaks of ascorbic acid (AA), dopamine (DA), and uric acid (UA) could be
well separated and the peak-to-peak separations are 204 mV (AA-DA) and 144 mV (DA
UA), respectively. Moreover, the linear response ranges for the determination of
1 * 10-8 mol/L~1 * 10-6 mol/L and 1 * 10-6 mol/L~8 * 10-5 mol/L with the
detection limit 6.0 * 10-9 mol/L (S/N = 3). The proposed Cu2O-RGO/GCE was further
applied to the determination of DA in dopamine hydrochloride injections with
satisfactory results.
PMID- 29329207
TI - Arnica Tincture Cures Cutaneous Leishmaniasis in Golden Hamsters.
AB - In search for potential therapeutic alternatives to existing treatments for
cutaneous Leishmaniasis, we have investigated the effect of Arnica tincture Ph.
Eur. (a 70% hydroethanolic tincture prepared from flowerheads of Arnica montana
L.) on the lesions caused by infection with Leishmania braziliensis in a model
with golden hamsters. The animals were treated topically with a daily single dose
of the preparation for 28 days. Subsequently, the healing process was monitored
by recording the lesion size in intervals of 15 days up to day 90. As a result,
Arnica tincture fully cured three out of five hamsters while one animal showed an
improvement and another one suffered from a relapse. This result was slightly
better than that obtained with the positive control, meglumine antimonate, which
cured two of five hamsters while the other three showed a relapse after 90 days.
This result encourages us to further investigate the potential of Arnica tincture
in the treatment of cutaneous Leishmaniasis.
PMID- 29329208
TI - Advances in Molecular Profiling and Categorisation of Pancreatic Adenocarcinoma
and the Implications for Therapy.
AB - Pancreatic ductal adenocarcinoma (PDAC) continues to be a disease with poor
outcomes and short-lived treatment responses. New information is emerging from
genome sequencing identifying potential subgroups based on somatic and germline
mutations. A variety of different mutations and mutational signatures have been
identified; the driver mutation in around 93% of PDAC is KRAS, with other
recorded alterations being SMAD4 and CDKN2A. Mutations in the deoxyribonucleic
acid (DNA) damage repair pathway have also been investigated in PDAC and multiple
clinical trials are ongoing with DNA-damaging agents. Rare mutations in BRAF and
microsatellite instability (MSI) have been reported in about 1-3% of patients
with PDAC, and agents used in other cancers to target these have also shown some
promise. Immunotherapy is a developing field, but has failed to demonstrate
benefits in PDAC to date. While many trials have failed to improve outcomes in
this deadly disease, there is optimism that by developing a better understanding
of the translational aspects of this cancer, future informed therapeutic
strategies may prove more successful.
PMID- 29329210
TI - An Over 90 dB Intra-Scene Single-Exposure Dynamic Range CMOS Image Sensor Using a
3.0 MUm Triple-Gain Pixel Fabricated in a Standard BSI Process.
AB - To respond to the high demand for high dynamic range imaging suitable for moving
objects with few artifacts, we have developed a single-exposure dynamic range
image sensor by introducing a triple-gain pixel and a low noise dual-gain readout
circuit. The developed 3 MUm pixel is capable of having three conversion gains.
Introducing a new split-pinned photodiode structure, linear full well reaches 40
ke-. Readout noise under the highest pixel gain condition is 1 e- with a low
noise readout circuit. Merging two signals, one with high pixel gain and high
analog gain, and the other with low pixel gain and low analog gain, a single
exposure dynamic rage (SEHDR) signal is obtained. Using this technology, a
1/2.7", 2M-pixel CMOS image sensor has been developed and characterized. The
image sensor also employs an on-chip linearization function, yielding a 16-bit
linear signal at 60 fps, and an intra-scene dynamic range of higher than 90 dB
was successfully demonstrated. This SEHDR approach inherently mitigates the
artifacts from moving objects or time-varying light sources that can appear in
the multiple exposure high dynamic range (MEHDR) approach.
PMID- 29329209
TI - Gentamicin Sulfate PEG-PLGA/PLGA-H Nanoparticles: Screening Design and
Antimicrobial Effect Evaluation toward Clinic Bacterial Isolates.
AB - Nanotechnology is a promising approach both for restoring or enhancing activity
of old and conventional antimicrobial agents and for treating intracellular
infections by providing intracellular targeting and sustained release of drug
inside infected cells. The present paper introduces a formulation study of
gentamicin loaded biodegradable nanoparticles (Nps). Solid-oil-in water technique
was studied for gentamicin sulfate nanoencapsulation using uncapped Polylactide
co-glycolide (PLGA-H) and Polylactide-co-glycolide-co-Polyethylenglycol (PLGA
PEG) blends. Screening design was applied to optimize: drug payload, Nps size and
size distribution, stability and resuspendability after freeze-drying. PLGA-PEG
concentration resulted most significant factor influencing particles size and
drug content (DC): 8 w/w% DC and 200 nm Nps were obtained. Stirring rate resulted
most influencing factor for size distribution (PDI): 700 rpm permitted to obtain
homogeneous Nps dispersion (PDI = 1). Further experimental parameters
investigated, by 23 screening design, were: polymer blend composition (PLGA-PEG
and PLGA-H), Polyvinylalcohol (PVA) and methanol concentrations into aqueous
phase. Drug content was increased to 10.5 w/w%. Nanoparticle lyophilization was
studied adding cryoprotectants, polyvinypirrolidone K17 and K32, and
sodiumcarboxymetylcellulose. Freeze-drying protocol was optimized by a mixture
design. A freeze-dried Nps powder free resuspendable with stable Nps size and
payload, was developed. The powder was tested on clinic bacterial isolates
demonstrating that after encapsulation, gentamicin sulfate kept its activity.
PMID- 29329211
TI - Causation of Acute Flaccid Paralysis by Myelitis and Myositis in Enterovirus-D68
Infected Mice Deficient in Interferon alphabeta/gamma Receptor Deficient Mice.
AB - Enterovirus D68 (EV-D68) caused a large outbreak in the summer and fall of 2014
in the United States. It causes serious respiratory disease, but causation of
associated paralysis is controversial, because the virus is not routinely
identified in cerebrospinal fluid. To establish clinical correlates with human
disease, we evaluated EV-D68 infection in non-lethal paralysis mouse models. Ten
day-old mice lacking interferon responses were injected intraperitoneally with
the virus. Paralysis developed in hindlimbs. After six weeks of paralysis, the
motor neurons were depleted due to viral infection. Hindlimb muscles were also
infected and degenerating. Even at the earliest stage of paralysis, muscles were
still infected and were degenerating, in addition to presence of virus in the
spinal cord. To model natural respiratory infection, five-day-old mice were
infected intranasally with EV-D68. Two of the four infected mice developed
forelimb paralysis. The affected limbs had muscle disease, but no spinal cord
infection was detected. The unique contributions of this study are that EV-D68
causes paralysis in mice, and that causation by muscle disease, with or without
spinal cord disease, may help to resolve the controversy that the virus can cause
paralysis, even if it cannot be identified in cerebrospinal fluid.
PMID- 29329212
TI - Study of the Thermal Properties and the Fire Performance of Flame Retardant
Organic PCM in Bulk Form.
AB - The implementation of organic phase change materials (PCMs) in several
applications such as heating and cooling or building comfort is an important
target in thermal energy storage (TES). However, one of the major drawbacks of
organic PCMs implementation is flammability. The addition of flame retardants to
PCMs or shape-stabilized PCMs is one of the approaches to address this problem
and improve their final deployment in the building material sector. In this
study, the most common organic PCM, Paraffin RT-21, and fatty acids mixtures of
capric acid (CA), myristic acid (MA), and palmitic acid (PA) in bulk, were tested
to improve their fire reaction. Several flame retardants, such as ammonium
phosphate, melamine phosphate, hydromagnesite, magnesium hydroxide, and aluminum
hydroxide, were tested. The properties of the improved PCM with flame retardants
were characterized by thermogravimetric analyses (TGA), the dripping test, and
differential scanning calorimetry (DSC). The results for the dripping test show
that fire retardancy was considerably enhanced by the addition of hydromagnesite
(50 wt %) and magnesium hydroxide (50 wt %) in fatty acids mixtures. This will
help the final implementation of these enhanced PCMs in building sector. The
influence of the addition of flame retardants on the melting enthalpy and
temperatures of PCMs has been evaluated.
PMID- 29329213
TI - A Cross-Sectional Study of the Association between Infant Hepatitis B Vaccine
Exposure in Boys and the Risk of Adverse Effects as Measured by Receipt of
Special Education Services.
AB - The National Center for Education Statistics reported that between 1990-2005 the
number of children receiving special education services (SES) rose significantly,
and then, from 2004-2012, the number declined significantly. This coincided with
the introduction of Thimerosal-containing hepatitis B vaccine in 1991, and the
subsequent introduction of Thimerosal-reduced hepatitis B vaccine in the early
2000s. This study examined the potential relationship between infant exposure to
mercury from three doses of Thimerosal-containing hepatitis B vaccine and the
risk of boys being adversely affected (as measured by receipt of SES). This cross
sectional study examined 1192 boys (weighted n = 24,537,123) 7-8 years of age
(born: 1994-2007) from the combined 2001-2014 National Health and Nutritional
Examination Survey (NHANES). Survey logistic regression modeling revealed that an
exposed population receiving three doses of infant Thimerosal-containing
hepatitis B vaccine (weighted n = 11,186,579), in comparison to an unexposed
population (weighted n = 704,254), were at an increased risk of receipt of SES.
This association was robust (crude odds ratio = 10.143, p = 0.0232), even when
considering covariates, such as race and socioeconomic status (adjusted odds
ratio = 9.234, p = 0.0259). Survey frequency modeling revealed that receipt of
SES for the population that was exposed to three doses of Thimerosal-containing
hepatitis B vaccine in infancy (12.91%) was significantly higher than the
unexposed population (1.44%) (prevalence ratio = 8.96, p = 0.006, prevalence
attributable rate = 0.1147). Despite the limitation of this cross-sectional study
not being able to ascribe a direct cause-and-effect relationship between exposure
and outcome, it is estimated that an additional 1.2 million boys received SES
with excess education costs of about United States (US) $180 billion associated
with exposure to Thimerosal-containing hepatitis B vaccine. By contrast, exposure
to Thimerosal-reduced hepatitis B vaccine was not associated with an increased
risk of receiving SES. Therefore, routine childhood vaccination is important to
reduce the morbidity and mortality of infectious diseases, but every effort
should be made to eliminate Thimerosal from all vaccines.
PMID- 29329214
TI - Analysis of Emission Effects Related to Drivers' Compliance Rates for Cooperative
Vehicle-Infrastructure System at Signalized Intersections.
AB - Unknown remaining time of signal phase at a signalized intersection generally
results in extra accelerations and decelerations that increase variations of
operating conditions and thus emissions. A cooperative vehicle-infrastructure
system can reduce unnecessary speed changes by establishing communications
between vehicles and the signal infrastructure. However, the environmental
benefits largely depend on drivers' compliance behaviors. To quantify the effects
of drivers' compliance rates on emissions, this study applied VISSIM 5.20
(Planung Transport Verkehr AG, Karlsruhe, Germany) to develop a simulation model
for a signalized intersection, in which light duty vehicles were equipped with a
cooperative vehicle-infrastructure system. A vehicle-specific power (VSP)-based
model was used to estimate emissions. Based on simulation data, the effects of
different compliance rates on VSP distributions, emission factors, and total
emissions were analyzed. The results show the higher compliance rate decreases
the proportion of VSP bin = 0, which means that the frequencies of braking and
idling were lower and light duty vehicles ran more smoothly at the intersection
if more light duty vehicles complied with the cooperative vehicle-infrastructure
system, and emission factors for light duty vehicles decreased significantly as
the compliance rate increased. The case study shows higher total emission
reductions were observed with higher compliance rate for all of CO2, NOx, HC, and
CO emissions. CO2 was reduced most significantly, decreased by 16% and 22% with
compliance rates of 0.3 and 0.7, respectively.
PMID- 29329216
TI - An Introduction to Integrative Genomics and Systems Medicine in Cancer.
AB - In this Special Issue (SI), with a theme of "Integrative Genomics and Systems
Medicine in Cancer", we have collected a total of 12 research and review articles
from researchers in the field of genomics and systems medicine[...].
PMID- 29329217
TI - Prey Acceptability and Preference of Oenopia conglobata (Coleoptera:
Coccinellidae), a Candidate for Biological Control in Urban Green Areas.
AB - Oenopia conglobata is one of the most common ladybird species in urban green
areas of the Mediterranean region. We have obtained data about its prey
acceptability and prey preferences. In a laboratory experiment, we investigated
the acceptability of seven aphid and one psyllid species as prey for this
coccinellid: the aphids Chaitophorus populeti, Aphis gossypii, Aphis
craccivoraMonelliopsis caryae, Eucallipterus tiliae, Aphis nerii (on white
poplar, pomegranate, false acacia, black walnut, lime, and oleander,
respectively), and the psyllid Acizziajamatonica on Persian silk tree. These
species are abundant in urban green areas in the Mediterranean region. In
addition, we tested the acceptability of Rhopalosiphum padi on barley, an aphid
species easily reared in the laboratory. We also tested preferences of the
predator in cafeteria experiments with three aphid species and one aphid and the
psyllid. Adults and larvae of the coccinellid accepted all of the preys offered,
except A. nerii, with a clear preference for M. caryae. The predator also showed
preference for M. caryae when it was offered in a cafeteria experiment with other
aphid species or with the psyllid. The aphid R. padi obtained a good
acceptability and could be used for rearing O. conglobata in the laboratory.
PMID- 29329215
TI - Dietary Supplement of Large Yellow Tea Ameliorates Metabolic Syndrome and
Attenuates Hepatic Steatosis in db/db Mice.
AB - Yellow tea has been widely recognized for its health benefits. However, its
effects and mechanism are largely unknown. The current study investigated the
mechanism of dietary supplements of large yellow tea and its effects on metabolic
syndrome and the hepatic steatosis in male db/db mice. Our data showed that
dietary supplements of large yellow tea and water extract significantly reduced
water intake and food consumption, lowered the serum total and low-density
lipoprotein cholesterol and triglyceride levels, and significantly reduced blood
glucose level and increased glucose tolerance in db/db mice when compared to
untreated db/db mice. In addition, the dietary supplement of large yellow tea
prevented the fatty liver formation and restored the normal hepatic structure of
db/db mice. Furthermore, the dietary supplement of large yellow tea obviously
reduced the lipid synthesis related to gene fatty acid synthase, the sterol
regulatory element-binding transcription factor 1 and acetyl-CoA carboxylase
alpha, as well as fatty acid synthase and sterol response element-binding protein
1 expression, while the lipid catabolic genes were not altered in the liver of
db/db mice. This study substantiated that the dietary supplement of large yellow
tea has potential as a food additive for ameliorating type 2 diabetes-associated
symptoms.
PMID- 29329218
TI - Molecular and Physiological Effects on the Small Intestine of Weaner Pigs
Following Feeding with Deoxynivalenol-Contaminated Feed.
AB - We intended to assess how exposure of piglets to deoxynivalenol (DON)
contaminated feed impacted their growth, immune response and gut development.
Piglets were fed traditional Phase I, Phase II and Phase III diets with the
control group receiving 0.20-0.40 ppm DON (referred to as the Control group) and
treatment group receiving much higher level of DON-contaminated wheat (3.30-3.80
ppm; referred to as DON-contaminated group). Feeding a DON-contaminated diet had
no impact on average daily feed intake (ADFI) (p < 0.08) or average daily gain
(ADG) (p > 0.10) but it did significantly reduce body weight over time relative
to the control piglets (p < 0.05). Cytokine analysis after initial exposure to
the DON-contaminated feed did not result in significant differences in serum
interleukin (IL) IL1beta, IL-8, IL-13, tumor necrosis factor (TNF)-alpha or
interferon (IFN)-gamma. After day 24, no obvious changes in jejunum or ileum gut
morphology, histology or changes in gene expression for IL-1beta, IL-6, IL-10,
TNFalpha, or Toll-like receptor (TLR)-4 genes. IL-8 showed a trend towards
increased expression in the ileum in DON-fed piglets. A significant increase in
gene expression for claudin (CLDN) 7 gene expression and a trend towards
increased CLDN 2-expression was observed in the ileum in piglets fed the highly
DON-contaminated wheat. Because CLDN localization was not negatively affected, we
believe that it is unlikely that gut permeability was affected. Exposure to DON
contaminated feed did not significantly impact weaner piglet performance or gut
physiology.
PMID- 29329219
TI - Modification of Boc-Protected CAN508 via Acylation and Suzuki-Miyaura Coupling.
AB - The cyclin-dependent kinase inhibitor, CAN508, was protected with di-tert-butyl
dicarbonate to access the amino-benzoylated pyrazoles. The bromo derivatives were
further arylated by Suzuki-Miyaura coupling using the XPhos Pd G2 pre-catalyst.
The coupling reaction provided generally the para-substituted benzoylpyrazoles in
the higher yields than the meta-substituted ones. The Boc groups were only
utilized as directing functionalities for the benzoylation step and were
hydrolyzed under conditions of Suzuki-Miyaura coupling, which allowed for
elimination of the additional deprotection step.
PMID- 29329220
TI - Electrostatic Deposition of Large-Surface Graphene.
AB - This work describes a method for electrostatic deposition of graphene over a
large area using controlled electrostatic exfoliation from a Highly Ordered
Pyrolytic Graphite (HOPG) block. Deposition over 130 * 130 um2 with 96% coverage
is achieved, which contrasts with sporadic micro-scale depositions of graphene
with little control from previous works on electrostatic deposition. The
deposition results are studied by Raman micro-spectroscopy and hyperspectral
analysis using large fields of view to allow for the characterization of the
whole deposition area. Results confirm that laser pre-patterning of the HOPG
block prior to cleaving generates anchor points favoring a more homogeneous and
defect-free HOPG surface, yielding larger and more uniform graphene depositions.
We also demonstrate that a second patterning of the HOPG block just before
exfoliation can yield features with precisely controlled geometries.
PMID- 29329221
TI - High-Temperature Sensor Based on Fabry-Perot Interferometer in Microfiber Tip.
AB - A miniaturized tip Fabry-Perot interferometer (tip-FPI) is proposed for high
temperature sensing. It is simply fabricated for the first time by splicing a
short length of microfiber (MF) to the cleaved end of a standard single mode
fiber (SMF) with precise control of the relative cross section position. Such a
MF acts as a Fabry-Perot (FP) cavity and serves as a tip sensor. A change in
temperature modifies the length and refractive index of the FP cavity, and then a
corresponding change in the reflected interference spectrum can be observed. High
temperatures of up to 1000 degrees C are measured in the experiments, and a high
sensitivity of 13.6 pm/ degrees C is achieved. This compact sensor, with tip
diameter and length both of tens of microns, is suitable for localized detection,
especially in harsh environments.
PMID- 29329222
TI - The Influence of EGFR Inactivation on the Radiation Response in High Grade
Glioma.
AB - Lack of effectiveness of radiation therapy may arise from different factors such
as radiation induced receptor tyrosine kinase activation and cell repopulation;
cell capability to repair radiation induced DNA damage; high grade glioma (HGG)
tumous heterogeneity, etc. In this study, we analyzed the potential of targeting
epidermal growth factor receptor (EGFR) in inducing radiosensitivity in two human
HGG cell lines (11 and 15) that displayed similar growth patterns and expressed
the receptor protein at the cell surface. We found that 15 HGG cells that express
more EGFR at the cell surface were more sensitive to AG556 (an EGFR inhibitor),
compared to 11 HGG cells. Although in line 15 the effect of the inhibitor was
greater than in line 11, it should be noted that the efficacy of this small
molecule EGFR inhibitor as monotherapy in both cell lines has been modest, at
best. Our data showed a slight difference in the response to radiation of the HGG
cell lines, three days after the treatment, with line 15 responding better than
line 11. However, both cell lines responded to ionizing radiation in the same
way, seven days after irradiation. EGFR inhibition induced radiosensitivity in 11
HGG cells, while, in 15 HGG cells, the effect of AG556 treatment on radiation
response was almost nonexistent.
PMID- 29329224
TI - Melanin-Based Functional Materials.
AB - Melanin biopolymers are currently the focus of growing interest for a broad range
of applications at the cutting edge of biomedical research and technology. This
Special Issue presents a collection of papers dealing with melanin-type
materials, e.g., polydopamine, for classic and innovative applications, offering
a stimulating perspective of current trends in the field. Besides basic
scientists, the Special Issue is directed to researchers from industries and
companies that are willing to invest in melanin research for innovative and
inspiring solutions.
PMID- 29329225
TI - Optical Fiber Demodulation System with High Performance for Assessing Fretting
Damage of Steam Generator Tubes.
AB - In order to access the fretting damage of the steam generator tube (SGT), a fast
fiber Fabry-Perot (F-P) non-scanning correlation demodulation system based on a
super luminescent light emitting diode (SLED) was performed. By demodulating the
light signal coming out from the F-P force sensor, the radial collision force
between the SGT and the tube support plate (TSP) was interrogated. For higher
demodulation accuracy, the effects of the center wavelength, bandwidth, and
spectrum noise of SLED were discussed in detail. Specially, a piezoelectric
ceramic transducer (PZT) modulation method was developed to get rid of the
interference of mode coupling induced by different types of fiber optics in the
demodulation system. The reflectivity of optical wedge and F-P sensor was
optimized. Finally, the demodulation system worked well in a 1:1 steam generator
test loop and successfully demodulated a force signal of 32 N with a collision
time of 2 ms.
PMID- 29329226
TI - Plils: A Practical Indoor Localization System through Less Expensive Wireless
Chips via Subregion Clustering.
AB - Reducing costs is a pragmatic method for promoting the widespread usage of indoor
localization technology. Conventional indoor localization systems (ILSs) exploit
relatively expensive wireless chips to measure received signal strength for
positioning. Our work is based on a cheap and widely-used commercial off-the
shelf (COTS) wireless chip, i.e., the Nordic Semiconductor nRF24LE1, which has
only several output power levels, and proposes a new power level based-ILS,
called Plils. The localization procedure incorporates two phases: an offline
training phase and an online localization phase. In the offline training phase, a
self-organizing map (SOM) is utilized for dividing a target area into k
subregions, wherein their grids in the same subregion have similar fingerprints.
In the online localization phase, the support vector machine (SVM) and back
propagation (BP) neural network methods are adopted to identify which subregion a
tagged object is located in, and calculate its exact location, respectively. The
reasonable value for k has been discussed as well. Our experiments show that
Plils achieves 75 cm accuracy on average, and is robust to indoor obstacles.
PMID- 29329223
TI - Mast Cells: Key Contributors to Cardiac Fibrosis.
AB - Historically, increased numbers of mast cells have been associated with fibrosis
in numerous cardiac pathologies, implicating mast cells in the development of
cardiac fibrosis. Subsequently, several approaches have been utilised to
demonstrate a causal role for mast cells in animal models of cardiac fibrosis
including mast cell stabilising compounds, rodents deficient in mast cells, and
inhibition of the actions of mast cell-specific proteases such as chymase and
tryptase. Whilst most evidence supports a pro-fibrotic role for mast cells, there
is evidence that in some settings these cells can oppose fibrosis. A major gap in
our current understanding of cardiac mast cell function is identification of the
stimuli that activate these cells causing them to promote a pro-fibrotic
environment. This review will present the evidence linking mast cells to cardiac
fibrosis, as well as discuss the major questions that remain in understanding how
mast cells contribute to cardiac fibrosis.
PMID- 29329227
TI - Fermentation-Guided Natural Products Isolation of a Grape Berry Triacylglyceride
that Enhances Ethyl Ester Production.
AB - A full understanding of the origin, formation and degradation of volatile
compounds that contribute to wine aroma is required before wine style can be
effectively managed. Fractionation of grapes represents a convenient and robust
method to simplify the grape matrix to enhance our understanding of the grape
contribution to volatile compound production during yeast fermentation. In this
study, acetone extracts of both Riesling and Cabernet Sauvignon grape berries
were fractionated and model wines produced by spiking aliquots of these grape
fractions into model grape juice must and fermented. Non-targeted SPME-GCMS
analyses of the wines showed that several medium chain fatty acid ethyl esters
were more abundant in wines made by fermenting model musts spiked with certain
fractions. Further fractionation of the non-polar fractions and fermentation of
model must after addition of these fractions led to the identification of a
mixture of polyunsaturated triacylglycerides that, when added to fermenting model
must, increase the concentration of medium chain fatty acid ethyl esters in
wines. Dosage-response fermentation studies with commercially-available
trilinolein revealed that the concentration of medium chain fatty acid ethyl
esters can be increased by the addition of this triacylglyceride to model musts.
This work suggests that grape triacylglycerides can enhance the production of
fermentation-derived ethyl esters and show that this fractionation method is
effective in segregating precursors or factors involved in altering the
concentration of fermentation volatiles.
PMID- 29329229
TI - Chemical Composition and Evaluation of the Biological Properties of the Essential
Oil of the Dietary Phytochemical Lippia citriodora.
AB - The aim of the study was to characterize the chemical composition and biological
properties of the essential oil from the plant Lippia citriodora grown in Greece.
The essential oil volatiles were analyzed by gas chromatography-mass spectrometry
GC-MS indicating citral as the major component. Tauhe antimicrobial properties
were assayed using the disk diffusion method and the minimum inhibitory and non
inhibitory concentration values were determined. Listeria monocytogenes,
Staphylococcus epidermidis, Staphylococcus aureus, Saccharomyces cerevisiae, and
Aspergillus niger were sensitive to Lippia citriodora oil, but not Escherichia
coli, Salmonella Enteritidis, Salmonella typhimurium, and Pseudomonas fragi.
Adversely, all microbes tested were sensitive to citral. 2,2-Diphenyl-1
picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)
(ABTS) assays were used to assess direct antioxidant activity, which proved to be
weak for both agents, while comet assay was utilized to study the cytoprotective
effects against H2O2-induced oxidative damage in Jurkat cells. Interestingly, the
oil showed a more profound cytoprotective effect compared to citral. The
antiproliferative activity was evaluated in a panel of cancer cell lines using
the sulforhodamine B (SRB) and 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-S
(phenylamino) carbonyl-2-tetrazolium hydroxide (XTT) assays and both agents
demonstrated potent antiproliferative activity with citral being more cytotoxic
than the oil. Taken together, the essential oil of Lippia citriodora and its
major component, citral, exert diverse biological properties worthy of further
investigation.
PMID- 29329228
TI - Current NMR Techniques for Structure-Based Drug Discovery.
AB - A variety of nuclear magnetic resonance (NMR) applications have been developed
for structure-based drug discovery (SBDD). NMR provides many advantages over
other methods, such as the ability to directly observe chemical compounds and
target biomolecules, and to be used for ligand-based and protein-based
approaches. NMR can also provide important information about the interactions in
a protein-ligand complex, such as structure, dynamics, and affinity, even when
the interaction is too weak to be detected by ELISA or fluorescence resonance
energy transfer (FRET)-based high-throughput screening (HTS) or to be
crystalized. In this study, we reviewed current NMR techniques. We focused on
recent progress in NMR measurement and sample preparation techniques that have
expanded the potential of NMR-based SBDD, such as fluorine NMR (19F-NMR)
screening, structure modeling of weak complexes, and site-specific isotope
labeling of challenging targets.
PMID- 29329230
TI - Metagenomic Virome Analysis of Culex Mosquitoes from Kenya and China.
AB - Many blood-feeding arthropods are known vectors of viruses that are a source of
unprecedented global health concern. Mosquitoes are an integral part of these
arthropod vectors. Advancements in next-generation sequencing and bioinformatics
has expanded our knowledge on the richness of viruses harbored by arthropods. In
the present study, we applied a metagenomic approach to determine the
intercontinental virome diversity of Culex quinquefasciatus and Culex
tritaeniorhynchus in Kwale, Kenya and provinces of Hubei and Yunnan in China. Our
results showed that viromes from the three locations were strikingly diverse and
comprised 30 virus families specific to vertebrates, invertebrates, plants, and
protozoa as well as unclassified group of viruses. Though sampled at different
times, both Kwale and Hubei mosquito viromes were dominated by vertebrate
viruses, in contrast to the Yunnan mosquito virome, which was dominated by insect
specific viruses. However, each virome was unique in terms of virus proportions
partly influenced by type of ingested meals (blood, nectar, plant sap,
environment substrates). The dominant vertebrate virus family in the Kwale virome
was Papillomaviridae (57%) while in Hubei it was Herpesviridae (30%) and the
Yunnan virome was dominated by an unclassified viruses group (27%). Given that
insect-specific viruses occur naturally in their hosts, they should be the basis
for defining the viromes. Hence, the dominant insect-specific viruses in Kwale,
Hubei, and Yunnan were Baculoviridae, Nimaviridae and Iflaviridae, respectively.
Our study is preliminary but contributes to growing and much needed knowledge, as
mosquito viromes could be manipulated to prevent and control pathogenic
arboviruses.
PMID- 29329231
TI - Development of a Cytocompatible Scaffold from Pig Immature Testicular Tissue
Allowing Human Sertoli Cell Attachment, Proliferation and Functionality.
AB - Cryopreservation of immature testicular tissue before chemo/radiotherapy is the
only option to preserve fertility of cancer-affected prepubertal boys. To avoid
reintroduction of malignant cells, development of a transplantable scaffold by
decellularization of pig immature testicular tissue (ITT) able to support
decontaminated testicular cells could be an option for fertility restoration in
these patients. We, therefore, compared decellularization protocols to produce a
cytocompatible scaffold. Fragments of ITT from 15 piglets were decellularized
using three protocols: sodium dodecyl sulfate (SDS)-Triton (ST), Triton-SDS
Triton (TST) and trypsin 0.05%/ethylenediaminetetraacetic acid (EDTA) 0.02%
Triton (TET) with varying detergent concentrations. All protocols were able to
lower DNA levels. Collagen retention was demonstrated in all groups except ST 1%,
and a significant decrease in glycosaminoglycans was observed in the TST 1% and
TET 1% groups. When Sertoli cells (SCs) were cultured with decellularized tissue,
no signs of cytotoxicity were detected. A higher SC proliferation rate and
greater stem cell factor secretion were observed than with SCs cultured without
scaffold. ST 0.01% and TET 3% conditions offered the best compromise in terms of
DNA elimination and extracellular matrix (ECM) preservation, while ensuring good
attachment, proliferation and functionality of human SCs. This study demonstrates
the potential of using decellularized pig ITT for human testicular tissue
engineering purposes.
PMID- 29329232
TI - Novel 6- and 7-Substituted Coumarins with Inhibitory Action against Lipoxygenase
and Tumor-Associated Carbonic Anhydrase IX.
AB - A series of carboxamide derivatives of 6- and 7-substituted coumarins have been
prepared by an original procedure starting from the corresponding 6- or 7
hydroxycoumarins which were alkylated with ethyl iodoacetate, and the obtained
ester was converted to the corresponding carboxylic acids which were thereafter
reacted with a series of aromatic/aliphatic/heterocyclic amines leading to the
desired amides. The new derivatives were investigated as inhibitors of two
enzymes, human carbonic anhydrases (hCAs) and soy bean lipoxygenase (LOX).
Compounds 4a and 4b were potent LOX inhibitors, whereas many effective hCA IX
inhibitors (KIs in the range of 30.2-30.5 nM) were detected in this study. Two
compounds, 4b and 5b, showed the phenomenon of dual inhibition. Furthermore,
these coumarins did not significantly inhibit the widespread cytosolic isoforms
hCA I and II, whereas they were weak hCA IV inhibitors, making them hCA IX
selective inhibitors. As hCA IX and LOX are validated antitumor targets, these
results are promising for the investigation of novel drug targets involved in
tumorigenesis.
PMID- 29329234
TI - Poor People Are Hospitalized Three Times More for Mental Health Services than the
Non-Poor in Central Valley California.
AB - Introduction: Providing health insurance to the poor has become a standard policy
response to health disparities between the poor and the non-poor. It is often
assumed that if the poor people are given health insurance, they will use
preventative care, which will prevent more expensive emergency visits and
inpatient hospitalization, and in turn, it will save healthcare cost in the long
run. This paper presents the findings from our study in California about what
happens to the poor when they are given health insurance. The purpose of the
study was to understand how the healthcare system in California treats the poor
patients differently than the non-poor. Method: Using multivariate logistic
regressions, this study analyzed a large patient discharge data (PDD) from the
California Office of Statewide Planning and Development (OSHPD) for eight
counties in the Central Valley California (N = 423,640). First, utilizing
International Classification of Diseases (ICD 10) as diagnostic criteria, mental
health vs. non-mental health hospitalization rates were estimated. Second, health
insurance status was used as a proxy measure of poverty of the patients. Using
chi-Square, the probability of hospitalization for mental health services was
estimated based on their insurance types. Finally, using step-wise logistic
regression, the odds of mental health hospitalization was estimated conditional
on individual characteristics, health insurance types, and geographic
characteristics. Findings: When the poor people were given health insurance, they
were three times more likely to be hospitalized for mental health services than
the non-poor. The more than three-fold variation in mental health hospitalization
was not driven by demographic or geographic characteristics. The findings are new
and have important implications for the healthcare policies for the poor. Further
studies are needed to understand the extent to which the disproportionately high
rate of mental health hospitalizations of the poor are driven by the provider
induced needs.
PMID- 29329233
TI - Dose-Dependent Effects of Randomized Intraduodenal Whey-Protein Loads on Glucose,
Gut Hormone, and Amino Acid Concentrations in Healthy Older and Younger Men.
AB - Protein-rich supplements are used widely for the prevention and management of
malnutrition in older people. We have reported that healthy older, compared to
younger, adults have less suppression of energy intake by whey-protein-effects on
appetite-related hormones are unknown. The objective was to determine the effects
of intraduodenally administered whey-protein on glucose, gut hormone, and amino
acid concentrations, and their relation to subsequent ad libitum energy intake at
a buffet meal, in healthy older and younger men. Hydrolyzed whey-protein (30
kcal, 90 kcal, and 180 kcal) and a saline control (~0 kcal) were infused
intraduodenally for 60 min in 10 younger (19-29 years, 73 +/- 2 kg, 22 +/- 1
kg/m2) and 10 older (68-81 years, 79 +/- 2 kg, 26 +/- 1 kg/m2) healthy men in a
randomized, double-blind fashion. Plasma insulin, glucagon, gastric inhibitory
peptide (GIP), glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY),
and amino acid concentrations, but not blood glucose, increased, while ghrelin
decreased during the whey-protein infusions. Plasma GIP concentrations were
greater in older than younger men. Energy intake correlated positively with
plasma ghrelin and negatively with insulin, glucagon, GIP, GLP-1, PYY, and amino
acids concentrations (p < 0.05). In conclusion, intraduodenal whey-protein
infusions resulted in increased GIP and comparable ghrelin, insulin, glucagon,
GIP, GLP-1, PYY, and amino acid responses in healthy older and younger men, which
correlated to subsequent energy intake.
PMID- 29329236
TI - Gender-Associated Impact of Early Leucine Supplementation on Adult Predisposition
to Obesity in Rats.
AB - Early nutrition plays an important role in development and may constitute a
relevant contributor to the onset of obesity in adulthood. The aim of this study
was to evaluate the long-term impact of maternal leucine (Leu) supplementation
during lactation on progeny in rats. A chow diet, supplemented with 2% Leu, was
supplied during lactation (21 days) and, from weaning onwards, was replaced by a
standard chow diet. Then, at adulthood (6 months of age), this was replaced with
hypercaloric diets (either with high-fat (HF) or high-carbohydrate (HC) content),
for two months, to induce obesity. Female offspring from Leu-supplemented dams
showed higher increases in body weight and in body fat (62%) than their
respective controls; whereas males were somehow protected (15% less fat than the
corresponding controls). This profile in Leu-females was associated with altered
neuronal architecture at the paraventricular nucleus (PVN), involving
neuropeptide Y (NPY) fibers and impaired expression of neuropeptides and factors
of the mTOR signaling pathway in the hypothalamus. Interestingly, leptin and
adiponectin expression in adipose tissue at weaning and at the time before the
onset of obesity could be defined as early biomarkers of metabolic disturbance,
predisposing towards adult obesity under the appropriate environment.
PMID- 29329235
TI - A Review of the Biological Activities of Microalgal Carotenoids and Their
Potential Use in Healthcare and Cosmetic Industries.
AB - Carotenoids are natural pigments that play pivotal roles in many physiological
functions. The characteristics of carotenoids, their effects on health, and the
cosmetic benefits of their usage have been under investigation for a long time;
however, most reviews on this subject focus on carotenoids obtained from several
microalgae, vegetables, fruits, and higher plants. Recently, microalgae have
received much attention due to their abilities in producing novel bioactive
metabolites, including a wide range of different carotenoids that can provide for
health and cosmetic benefits. The main objectives of this review are to provide
an updated view of recent work on the health and cosmetic benefits associated
with carotenoid use, as well as to provide a list of microalgae that produce
different types of carotenoids. This review could provide new insights to
researchers on the potential role of carotenoids in improving human health.
PMID- 29329237
TI - mTOR Pathways in Cancer and Autophagy.
AB - TOR (target of rapamycin), an evolutionarily-conserved serine/threonine kinase,
acts as a central regulator of cell growth, proliferation and survival in
response to nutritional status, growth factor, and stress signals. It plays a
crucial role in coordinating the balance between cell growth and cell death,
depending on cellular conditions and needs. As such, TOR has been identified as a
key modulator of autophagy for more than a decade, and several deregulations of
this pathway have been implicated in a variety of pathological disorders,
including cancer. At the molecular level, autophagy regulates several survival or
death signaling pathways that may decide the fate of cancer cells; however, the
relationship between autophagy pathways and cancer are still nascent. In this
review, we discuss the recent cellular signaling pathways regulated by TOR, their
interconnections to autophagy, and the clinical implications of TOR inhibitors in
cancer.
PMID- 29329239
TI - Fine Regulation of Neutrophil Oxidative Status and Apoptosis by Ceruloplasmin and
Its Derivatives.
AB - Timely neutrophil apoptosis is an essential part of the resolution phase of acute
inflammation. Ceruloplasmin, an acute-phase protein, which is the predominant
copper-carrying protein in the blood, has been suggested to have a marked effect
on neutrophil life span. The present work is a comparative study on the effects
of intact holo-ceruloplasmin, its copper-free (apo-) and partially proteolyzed
forms, and synthetic free peptides RPYLKVFNPR (883-892) and RRPYLKVFNPRR (882
893) on polymorphonuclear leukocyte (PMNL, neutrophil) oxidant status and
apoptosis. The most pronounced effect on both investigated parameters was found
with copper-containing samples, namely, intact and proteolyzed proteins. Both
effectively reduced spontaneous and tumor necrosis factor-alpha (TNF-alpha)
induced extracellular and intracellular accumulation of superoxide radicals, but
induced a sharp increase in the oxidation of intracellular 2',7'
dichlorofluorescein upon short exposure. Therefore, intact and proteolyzed
ceruloplasmin have both anti- and pro-oxidant effects on PMNLs wherein the latter
effect is diminished by TNF-alpha and lactoferrin. Additionally, all compounds
investigated were determined to be inhibitors of delayed spontaneous apoptosis.
Intact enzyme retained its pro-survival activity, whereas proteolytic degradation
converts ceruloplasmin from a mild inhibitor to a potent activator of TNF-alpha
induced neutrophil apoptosis.
PMID- 29329240
TI - Effective Data-Driven Calibration for a Galvanometric Laser Scanning System Using
Binocular Stereo Vision.
AB - A new solution to the problem of galvanometric laser scanning (GLS) system
calibration is presented. Under the machine learning framework, we build a single
hidden layer feedforward neural network (SLFN)to represent the GLS system, which
takes the digital control signal at the drives of the GLS system as input and the
space vector of the corresponding outgoing laser beam as output. The training
data set is obtained with the aid of a moving mechanism and a binocular stereo
system. The parameters of the SLFN are efficiently solved in a closed form by
using extreme learning machine (ELM). By quantitatively analyzing the regression
precision with respective to the number of hidden neurons in the SLFN, we
demonstrate that the proper number of hidden neurons can be safely chosen from a
broad interval to guarantee good generalization performance. Compared to the
traditional model-driven calibration, the proposed calibration method does not
need a complex modeling process and is more accurate and stable. As the output of
the network is the space vectors of the outgoing laser beams, it costs much less
training time and can provide a uniform solution to both laser projection and 3D
reconstruction, in contrast with the existing data-driven calibration method
which only works for the laser triangulation problem. Calibration experiment,
projection experiment and 3D reconstruction experiment are respectively conducted
to test the proposed method, and good results are obtained.
PMID- 29329241
TI - Sino-Austrian High-Tech Acupuncture Network: Annual Report 2017.
AB - The Sino-Austrian High-Tech Acupuncture Research Network was founded in 2005 and
has been growing ever since. The network comprises many partners from China and
is highly involved in research and education activities. This report introduces
the network's activities in the year 2017.
PMID- 29329238
TI - Long-Chain Metabolites of Vitamin E: Metabolic Activation as a General Concept
for Lipid-Soluble Vitamins?
AB - Vitamins E, A, D and K comprise the class of lipid-soluble vitamins. For vitamins
A and D, a metabolic conversion of precursors to active metabolites has already
been described. During the metabolism of vitamin E, the long-chain metabolites
(LCMs) 13'-hydroxychromanol (13'-OH) and 13'-carboxychromanol (13'-COOH) are
formed by oxidative modification of the side-chain. The occurrence of these
metabolites in human serum indicates a physiological relevance. Indeed, effects
of the LCMs on lipid metabolism, apoptosis, proliferation and inflammatory
actions as well as tocopherol and xenobiotic metabolism have been shown.
Interestingly, there are several parallels between the actions of the LCMs of
vitamin E and the active metabolites of vitamin A and D. The recent findings that
the LCMs exert effects different from that of their precursors support their
putative role as regulatory metabolites. Hence, it could be proposed that the
mode of action of the LCMs might be mediated by a mechanism similar to vitamin A
and D metabolites. If the physiological relevance and this concept of action of
the LCMs can be confirmed, a general concept of activation of lipid-soluble
vitamins via their metabolites might be deduced.
PMID- 29329242
TI - Absorption and Metabolism of Phenolics from Digests of Polyphenol-Rich Potato
Extracts Using the Caco-2/HepG2 Co-Culture System.
AB - The bioactivity of dietary polyphenols depends upon gastrointestinal and hepatic
metabolism of secondary microbial phenolic metabolites generated via colonic
microbiota-mediated biotransformation. A polyphenol-rich potato extract (PRPE)
containing chlorogenic, caffeic, and ferulic acids and rutin was digested in a
dynamic multi-reactor gastrointestinal simulator of the human intestinal
microbial ecosystem (GI model). Simulated digestion showed extensive degradation
of the parent compounds and the generation of microbial phenolic metabolites. To
characterize the transport and metabolism of microbial phenolic metabolites
following digestion, a co-culture of intestinal Caco-2 and hepatic HepG2 cells
was exposed to the PRPE-derived digests obtained from the colonic vessels.
Following a 2 h incubation of the digesta with the Caco-2/HepG2 co-cultures,
approximately 10-15% of ferulic, dihydrocaffeic, and dihydroferulic acids and 3
5% of 3-hydroxybenzoic, 3-hydroxyphenylpropionic, and coumaric acids were
observed in the basolateral side, whereas 3-hydroxyphenylacetic acid,
phenylpropanoic acid, and cinnamic acid were not detected. Subsequent HepG2
cellular metabolism led to major increases in ferulic, dihydrocaffeic, 3
hydroxyphenylpropionic, and coumaric acids ranging from 160-370%. These findings
highlight the importance of hepatic metabolism towards the generation of
secondary metabolites of polyphenols despite low selective Caco-2 cellular uptake
of microbial phenolic metabolites.
PMID- 29329243
TI - Characteristics of BeiDou Navigation Satellite System Multipath and Its
Mitigation Method Based on Kalman Filter and Rauch-Tung-Striebel Smoother.
AB - Global Navigation Satellite System (GNSS) carrier phase measurement for short
baseline meets the requirements of deformation monitoring of large structures.
However, the carrier phase multipath effect is the main error source with double
difference (DD) processing. There are lots of methods to deal with the multipath
errors of Global Position System (GPS) carrier phase data. The BeiDou navigation
satellite System (BDS) multipath mitigation is still a research hotspot because
the unique constellation design of BDS makes it different to mitigate multipath
effects compared to GPS. Multipath error periodically repeats for its strong
correlation to geometry of satellites, reflective surface and antenna which is
also repetitive. We analyzed the characteristics of orbital periods of BDS
satellites which are consistent with multipath repeat periods of corresponding
satellites. The results show that the orbital periods and multipath periods for
BDS geostationary earth orbit (GEO) and inclined geosynchronous orbit (IGSO)
satellites are about one day but the periods of MEO satellites are about seven
days. The Kalman filter (KF) and Rauch-Tung-Striebel Smoother (RTSS) was
introduced to extract the multipath models from single difference (SD) residuals
with traditional sidereal filter (SF). Wavelet filter and Empirical mode
decomposition (EMD) were also used to mitigate multipath effects. The
experimental results show that the three filters methods all have obvious effect
on improvement of baseline accuracy and the performance of KT-RTSS method is
slightly better than that of wavelet filter and EMD filter. The baseline vector
accuracy on east, north and up (E, N, U) components with KF-RTSS method were
improved by 62.8%, 63.6%, 62.5% on day of year 280 and 57.3%, 53.4%, 55.9% on day
of year 281, respectively.
PMID- 29329245
TI - Underwater Object Segmentation Based on Optical Features.
AB - Underwater optical environments are seriously affected by various optical inputs,
such as artificial light, sky light, and ambient scattered light. The latter two
can block underwater object segmentation tasks, since they inhibit the emergence
of objects of interest and distort image information, while artificial light can
contribute to segmentation. Artificial light often focuses on the object of
interest, and, therefore, we can initially identify the region of target objects
if the collimation of artificial light is recognized. Based on this concept, we
propose an optical feature extraction, calculation, and decision method to
identify the collimated region of artificial light as a candidate object region.
Then, the second phase employs a level set method to segment the objects of
interest within the candidate region. This two-phase structure largely removes
background noise and highlights the outline of underwater objects. We test the
performance of the method with diverse underwater datasets, demonstrating that it
outperforms previous methods.
PMID- 29329244
TI - Infant Development at the Age of 6 Months in Relation to Feeding Practices, Iron
Status, and Growth in a Peri-Urban Community of South Africa.
AB - BACKGROUND: Evidence on the association between feeding practices, iron
deficiency, anaemia, stunting, and impaired psychomotor development during
infancy is limited. This study assessed the association between psychomotor
development with early feeding practices, growth, iron status, and anaemia.
METHODS: This was cross-sectional baseline data of a randomised controlled trial
which included 6-month-old infants and their mothers or primary caregivers (n =
750) in a peri-urban community in the North West province of South Africa. The
Kilifi Developmental Inventory and a parent rating scale were used to assess
psychomotor development. Feeding practices and anthropometric measurements were
based on the World Health Organisation (WHO) guidelines. Anaemia and iron status
were determined by blood sample analysis. RESULTS: Prevalence of anaemia and
stunting for the infants were 36.4% and 28.5%, respectively. Multiple regression
analysis showed that birth weight was related to combined psychomotor scores
(beta = -3.427 (-4.603, 1.891), p < 0.001), as well as parent rating scores (beta
= -0.843 (-1.507, -0.180), p = 0.013). Length-for-age z-scores were associated
with combined psychomotor scores (beta = -1.419 (-2.466, 0.373), p = 0.008), as
well as parent rating scores (beta = -0.747 (-1.483, -0.010), p = 0.047).
CONCLUSIONS: In this setting, with high prevalence of anaemia and stunting,
important associations between lower psychomotor development scores and
birthweight as well as length-for-age z-scores in 6-month-old infants were found.
These findings warrant further investigation to develop a greater understanding
of factors influencing the association between child growth and psychomotor
development within the first 1000 days of life.
PMID- 29329246
TI - Socioeconomic Inequalities in the Use of Healthcare Services: Comparison between
the Roma and General Populations in Spain.
AB - This paper explores whether the principles of horizontal and vertical equity in
healthcare are met by the Spanish national health system in the case of the Roma
and general populations. The 2011/2012 Spanish National Health Survey (n =
21,650) and the 2014 National Health Survey of the Spanish Roma Population (n =
1167) were analyzed. Use of healthcare services was measured in terms of visits
to a general practitioner (GP), visits to an emergency department, and
hospitalizations. Healthcare need was measured using (a) self-rated health and
(b) the reported number of chronic diseases. The Roma reported worse self-rated
health and a higher prevalence of chronic diseases. A redistributive effect
(increased healthcare service use among Roma and those in lower socio-economic
classes) was found for hospitalizations and emergency visits. This effect was
also observed in GP visits for women, but not for men. Vertical inequity was
observed in the general population but not in the Roma population for GP visits.
The results suggest the existence of horizontal inequity in the use of GP
services (Roma women), emergency department visits (Roma and general population),
and hospitalizations (Roma population) and of vertical inequity in the use of GP
services among the general population.
PMID- 29329248
TI - Performance Analysis of Millimeter-Wave Multi-hop Machine-to-Machine Networks
Based on Hop Distance Statistics.
AB - As an intrinsic part of the Internet of Things (IoT) ecosystem, machine-to
machine (M2M) communications are expected to provide ubiquitous connectivity
between machines. Millimeter-wave (mmWave) communication is another promising
technology for the future communication systems to alleviate the pressure of
scarce spectrum resources. For this reason, in this paper, we consider multi-hop
M2M communications, where a machine-type communication (MTC) device with the
limited transmit power relays to help other devices using mmWave. To be specific,
we focus on hop distance statistics and their impacts on system performances in
multi-hop wireless networks (MWNs) with directional antenna arrays in mmWave for
M2M communications. Different from microwave systems, in mmWave communications,
wireless channel suffers from blockage by obstacles that heavily attenuate line
of-sight signals, which may result in limited per-hop progress in MWNs. We
consider two routing strategies aiming at different types of applications and
derive the probability distributions of their hop distances. Moreover, we provide
their baseline statistics assuming the blockage-free scenario to quantify the
impact of blockages. Based on the hop distance analysis, we propose a method to
estimate the end-to-end performances (e.g., outage probability, hop count, and
transmit energy) of the mmWave MWNs, which provides important insights into
mmWave MWN design without time-consuming and repetitive end-to-end simulation.
PMID- 29329247
TI - A Simple Method to Measure Renal Function in Swine by the Plasma Clearance of
Iohexol.
AB - There is no simple method to measure glomerular filtration rate (GFR) in swine,
an established model for studying renal disease. We developed a protocol to
measure GFR in conscious swine by using the plasma clearance of iohexol. We used
two groups, test and validation, with eight animals each. Ten milliliters of
iohexol (6.47 g) was injected into the marginal auricular vein and blood samples
(3 mL) were collected from the orbital sinus at different points after injection.
GFR was determined using two models: two-compartment (CL2: all samples) and one
compartment (CL1: the last six samples). In the test group, CL1 overestimated CL2
by ~30%: CL2 = 245 +/- 93 and CL1 = 308 +/- 123 mL/min. This error was corrected
by a first-order polynomial quadratic equation to CL1, which was considered the
simplified method: SM = -47.909 + (1.176xCL1) - (0.00063968xCL12). The SM showed
narrow limits of agreement with CL2, a concordance correlation of 0.97, and a
total deviation index of 14.73%. Similar results were obtained for the validation
group. This protocol is reliable, reproducible, can be performed in conscious
animals, uses a single dose of the marker, and requires a reduced number of
samples, and avoids urine collection. Finally, it presents a significant
improvement in animal welfare conditions and handling necessities in experimental
trials.
PMID- 29329250
TI - Blood Flow and Continuous EEG Changes during Symptomatic Plateau Waves.
AB - Benign meningiomas uncommonly lead to significant cerebral edema, with only a few
cases previously reported in the medical literature. The present study describes
the case of a 49-year-old female who had a meningioma resection. She subsequently
developed malignant cerebral edema and had episodes that were initially
concerning for seizure activity. However, transient blood flow changes concerning
for intracranial pressure (ICP) crises, were demonstrated on electroencephalogram
(EEG) as well as noninvasive cerebral blood flow monitoring. The present case
highlights the importance of close monitoring in patients with post meningioma
resection cerebral edema because of the possibility of ICP crises.
PMID- 29329249
TI - Scaffolding for Repair: Understanding Molecular Functions of the SMC5/6 Complex.
AB - Chromosome organization, dynamics and stability are required for successful
passage through cellular generations and transmission of genetic information to
offspring. The key components involved are Structural maintenance of chromosomes
(SMC) complexes. Cohesin complex ensures proper chromatid alignment, condensin
complex chromosome condensation and the SMC5/6 complex is specialized in the
maintenance of genome stability. Here we summarize recent knowledge on the
composition and molecular functions of SMC5/6 complex. SMC5/6 complex was
originally identified based on the sensitivity of its mutants to genotoxic stress
but there is increasing number of studies demonstrating its roles in the control
of DNA replication, sister chromatid resolution and genomic location-dependent
promotion or suppression of homologous recombination. Some of these functions
appear to be due to a very dynamic interaction with cohesin or other repair
complexes. Studies in Arabidopsis indicate that, besides its canonical function
in repair of damaged DNA, the SMC5/6 complex plays important roles in regulating
plant development, abiotic stress responses, suppression of autoimmune responses
and sexual reproduction.
PMID- 29329251
TI - Pharmacological Investigation of the Anti-Inflammation and Anti-Oxidation
Activities of Diallyl Disulfide in a Rat Emphysema Model Induced by Cigarette
Smoke Extract.
AB - Diallyl disulfide (DADS) is the main organosulfur ingredient in garlic, with
known antioxidant and anti-inflammatory activities. The aim of the present study
was to investigate the effect of DADS on reducing the inflammation and redox
imbalance in a rat emphysema model that was induced by intraperitoneal injection
of cigarette smoke extract (CSE). Briefly, DADS exerted an anti-inflammation
effect on emphysema rats through decreasing cell influx in the bronchoalveolar
lavage fluid (BALF) and suppressing pro-inflammation cytokine production
including tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta),
interleukin-6 (IL-6) via inhibiting the NF-kappaB pathway. In addition, levels of
oxidative stress markers including malondialdehyde (MDA) and myeloperoxidase
(MPO) were reduced, while the activities of glutathione (GSH), glutathione
peroxidase (GSH-PX), superoxide dismutase (SOD) and total antioxidant capacity (T
AOC) were markedly enhanced by DADS. Moreover, MMP-9 and TIMP-1 expression were
down-regulated by DADS. Furthermore, the regulation effects of DADS on CD4+ and
CD8+ T cells were observed. In conclusion, these encouraging findings suggest
that DADS could be considered as a promising anti-inflammation and antioxidative
agent for the treatment of emphysema.
PMID- 29329255
TI - Peri-Implant Behavior of Sloped Shoulder Dental Implants Used for All-On-Four
Protocols: An Histomorphometric Analysis in Dogs.
AB - The aim of this study was to evaluate the soft tissue thickness and marginal bone
loss around dental implants with sloped micro-threaded shoulder (35 degrees
angle) in comparing with conventional design, inserted 35 degrees degrees
angulated in post extraction sockets and immediate loaded with temporary
prosthesis simulating the all-on-four protocol. Materials and Methods: Six fox
hound dogs received forty-eight post extraction dental implants with the same
diameter and length (Medentika, Germany), but with different neck configurations.
Two group of implants were inserted 1mm subcrestal. Control group has a micro
threaded neck and the Test group has a sloped microthreaded neck. Immediate
loading was applied using a constructed metallic structure. After three months,
soft and hard tissue levels were assessed by histomorphometric analysis. Results:
The mean soft tissue thickness (STT) was 2.5 +/- 0.2 mm for the Control group and
3.3 +/- 0.3 mm for Test group (p = 0.036), meanwhile the mean marginal bone loss
(MBL) was 1.53 +/- 0.34 mm for Control group and, 1.62 +/- 0.22 mm for Test group
(p > 0.05). Conclusions: Within the limitations of this experimental model in
dogs, the findings showed that dental implants with microthreaded and
microthreaded sloped necks installed in immediate post extraction sites with
immediate load, presented a comparable perimplant tissue behavior.
PMID- 29329254
TI - Low-Carbohydrate, High-Protein, High-Fat Diets Rich in Livestock, Poultry and
Their Products Predict Impending Risk of Type 2 Diabetes in Chinese Individuals
that Exceed Their Calculated Caloric Requirement.
AB - The evidence on the association between long-term low-carbohydrate, high-fat and
high-protein diets and type 2 diabetes (T2D) is controversial. Until now, data is
limited for Chinese populations, especially in considering the influence of extra
energy intake. In this paper, we aimed to investigate the association of low
carbohydrate, high-fat and high-protein diets with type 2 diabetes (T2D) risk in
populations consuming extra calories and those with normal caloric intake, We
also determined whether the association is mediated by insulin resistance (IR) or
beta-cell dysfunction. A total of 3644 subjects in the Harbin People's Health
Study (Cohort 1, 2008-2012) and 7111 subjects in the Harbin Cohort Study on Diet,
Nutrition and Chronic Non-Communicable Diseases (Cohort 2, 2010-2015) were
analyzed, with a median follow-up of 4.2 and 5.3 years, respectively.
Multivariate relative risks (RRs) and their 95% confidence intervals (95% CIs)
were calculated to estimate the association between low-carbohydrate, high-fat
and high-protein diet and T2D in logistic regression models. The multivariate RRs
(95% CIs) were 1.00, 2.24 (1.07, 4.72) and 2.29 (1.07, 4.88) (Ptrend = 0.04), and
1.00, 1.45 (0.91, 2.31) and 1.64 (1.03, 2.61) (Ptrend = 0.04) across tertiles of
low-carbohydrate, high-fat and high-protein diet scores in the population
consuming extra calories in Cohort 1 and Cohort 2, respectively. The association
was no longer significant after adjustment for livestock and its products, or
poultry and its products. The mediation analysis discovered that this association
in the population consuming extra calories was insulin resistance mediated, in
both Cohort 1 and Cohort 2. However, the association was not significant among
participants overall and participants with normal caloric intake. Our results
indicated that long-term low-carbohydrate, high-fat and high-protein diets were
associated with increased T2D risk among the population consuming extra calories,
which may be caused by higher intake of animal-origin fat and protein as well as
lower intake of vegetables, fruit and fiber. Additionally, the association was
mediated by IR. In the population consuming extra calories, reducing the intake
of livestock, poultry and their products and increasing the intake of vegetables,
fruit and fiber might protect this population from developing T2D.
PMID- 29329256
TI - Personalized Antidepressant Selection and Pathway to Novel Treatments: Clinical
Utility of Targeting Inflammation.
AB - Major depressive disorder (MDD) is a chronic condition that affects one in six
adults in the US during their lifetime. The current practice of antidepressant
medication prescription is a trial-and-error process. Additionally, over a third
of patients with MDD fail to respond to two or more antidepressant treatments.
There are no valid clinical markers to personalize currently available
antidepressant medications, all of which have similar mechanisms targeting
monoamine neurotransmission. The goal of this review is to summarize the recent
findings of immune dysfunction in patients with MDD, the utility of inflammatory
markers to personalize treatment selection, and the potential of targeting
inflammation to develop novel antidepressant treatments. To personalize
antidepressant prescription, a c-reactive protein (CRP)-matched treatment
assignment can be rapidly implemented in clinical practice with point-of-care
fingerstick tests. With this approach, 4.5 patients need to be treated for 1
additional remission as compared to a CRP-mismatched treatment assignment. Anti
cytokine treatments may be effective as novel antidepressants. Monoclonal
antibodies against proinflammatory cytokines, such as interleukin 6, interleukin
17, and tumor necrosis factor alpha, have demonstrated antidepressant effects in
patients with chronic inflammatory conditions who report significant depressive
symptoms. Additional novel antidepressant strategies targeting inflammation
include pharmaceutical agents that block the effect of systemic inflammation on
the central nervous system. In conclusion, inflammatory markers offer the
potential not only to personalize antidepressant prescription but also to guide
the development of novel mechanistically-guided antidepressant treatments.
PMID- 29329259
TI - Extreme Overvalued Beliefs: How Violent Extremist Beliefs Become "Normalized".
AB - Extreme overvalued beliefs (EOB) are rigidly held, non-deusional beliefs that are
the motive behind most acts of terrorism and mass shootings. EOBs are
differentiated from delusions and obsessions. The concept of an overvalued idea
was first described by Wernicke and later applied to terrorism by McHugh. Our
group of forensic psychiatrists (Rahman, Resnick, Harry) refined the definition
as an aid in the differential diagnosis seen in acts of violence. The form and
content of EOBs is discussed as well as group effects, conformity, and obedience
to authority. Religious cults such as The People's Temple, Heaven's Gate, Aum
Shinrikyo, and Islamic State (ISIS) and conspiracy beliefs such as
assassinations, moon-hoax, and vaccine-induced autism beliefs are discussed using
this construct. Finally, some concluding thoughts on countering violent
extremism, including its online presence is discussed utilizing information
learned from online eating disorders and consumer experience.
PMID- 29329258
TI - Association between Haem and Non-Haem Iron Intake and Serum Ferritin in Healthy
Young Women.
AB - Iron is an essential micronutrient for human health and inadequate intake may
result in iron deficiency (ID) or iron deficiency anaemia (IDA). Unlike other
recent studies investigating iron status in young women, this cross-sectional
study analysed dietary intake and biochemical data from healthy young (18-35
years) women (n = 299) to determine the association between both haem iron (HI)
and non-haem iron (NHI) intakes and serum ferritin (SF). Dietary restraint and
possible inflammation secondary to obesity were also measured and accounted for,
and energy intake was adjusted for using the residuals method. Independent
samples t-tests and chi-squared tests were performed, and factors found to be
significantly different between iron replete (IR) and ID/IDA participants were
analysed using general linear modelling. ID/IDA participants consumed
significantly lower total energy than iron replete (IR) (p = 0.003). Lower energy
intake was also associated with higher levels of dietary restraint (p = 0.001).
Both HI and NHI were positively associated with SF with HI was found to be a
stronger predictor (beta = 0.128, p = 0.009) than NHI (beta = 0.037, p = 0.028).
The study demonstrates that intake of both HI and NHI, as well as adequate
dietary energy, are associated with normal iron status levels in young women, and
that restrained eaters may be at greater risk of low iron status.
PMID- 29329260
TI - Effects of Zr Addition on Strengthening Mechanisms of Al-Alloyed High-Cr ODS
Steels.
AB - Oxide dispersion strengthened (ODS) steels with different contents of zirconium
(denoted as 16Cr ODS, 16Cr-0.3Zr ODS and 16Cr-0.6Zr ODS) were fabricated to
investigate the effects of Zr on strengthening mechanism of Al-alloyed 16Cr ODS
steel. Electron backscatter diffraction (EBSD) results show that the mean grain
size of ODS steels could be decreased by Zr addition. Transmission electron
microscope (TEM) results indicate that Zr addition could increase the number
density but decrease the mean diameter and inter-particle spacing of oxide
particles. Furthermore, it is also found that in addition to Y-Al-O
nanoparticles, Y-Zr-O oxides with finer size were observed in 16Cr-0.3Zr ODS and
16Cr-0.6Zr ODS steels. These changes in microstructure significantly increase the
yield strength (YS) and ultimate tensile strength (UTS) of ODS steels through
mechanisms of grain boundary strengthening and dispersion strengthening.
PMID- 29329261
TI - Sitting Posture Monitoring System Based on a Low-Cost Load Cell Using Machine
Learning.
AB - Sitting posture monitoring systems (SPMSs) help assess the posture of a seated
person in real-time and improve sitting posture. To date, SPMS studies reported
have required many sensors mounted on the backrest plate and seat plate of a
chair. The present study, therefore, developed a system that measures a total of
six sitting postures including the posture that applied a load to the backrest
plate, with four load cells mounted only on the seat plate. Various machine
learning algorithms were applied to the body weight ratio measured by the
developed SPMS to identify the method that most accurately classified the actual
sitting posture of the seated person. After classifying the sitting postures
using several classifiers, average and maximum classification rates of 97.20% and
97.94%, respectively, were obtained from nine subjects with a support vector
machine using the radial basis function kernel; the results obtained by this
classifier showed a statistically significant difference from the results of
multiple classifications using other classifiers. The proposed SPMS was able to
classify six sitting postures including the posture with loading on the backrest
and showed the possibility of classifying the sitting posture even though the
number of sensors is reduced.
PMID- 29329257
TI - Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review.
AB - Pyrazole and its derivatives are considered a pharmacologically important active
scaffold that possesses almost all types of pharmacological activities. The
presence of this nucleus in pharmacological agents of diverse therapeutic
categories such as celecoxib, a potent anti-inflammatory, the antipsychotic
CDPPB, the anti-obesity drug rimonabant, difenamizole, an analgesic, betazole, a
H2-receptor agonist and the antidepressant agent fezolamide have proved the
pharmacological potential of the pyrazole moiety. Owing to this diversity in the
biological field, this nucleus has attracted the attention of many researchers to
study its skeleton chemically and biologically. This review highlights the
different synthesis methods and the pharmacological properties of pyrazole
derivatives. Studies on the synthesis and biological activity of pyrazole
derivatives developed by many scientists around the globe are reported.
PMID- 29329262
TI - Contamination and Risk Assessment of Estrogens in Livestock Manure: A Case Study
in Jiangsu Province, China.
AB - This study investigated the occurrence and contamination risk of estrogens in
livestock manure in Jiangsu Province, China. Four estrogens-estriol (E3), 17beta
estradiol (17beta-E2), bisphenol A (BPA), and 17alpha-ethinyloestradiol (EE2)
were detected in livestock manure from hens, ducks, swine, and cows. The
respective mean concentrations of each estrogen found in these manures were
289.8, 334.1, 330.3, and 33.7 MUg/kg for E3; 38.6, 10.9, 52.9, and 38.8 MUg/kg
for 17beta-E2; 63.6, 48.7, 51.9, and 11.7 MUg/kg for BPA; and 14.3, 11.3, 25.1,
and 21.8 MUg/kg for EE2. Estrogens were most frequently detected at high
concentrations in the manure of finishing pigs, followed by the manure of growing
pigs and piglets. Estrogens can be partially degraded after banking up for seven
days; yet, great quantities of estrogens remain in livestock manure. The total
estradiol equivalent quantity (EEQt) estimated to be present in aquatic
environments but originating from livestock waste was 10.5 ng/L, which was
greater than the hazard baseline value (1 ng/L) and also higher than the proposed
lowest observable effect concentration (10 ng/L) of E2 in aquatic environments.
The results of our study demonstrate that livestock waste is an important source
of estrogens, which may potentially affect the hormonal metabolism of aquatic
organisms.
PMID- 29329263
TI - Effect of Radiological Countermeasures on Subjective Well-Being and Radiation
Anxiety after the 2011 Disaster: The Fukushima Health Management Survey.
AB - After the Fukushima Daiichi Nuclear Power Station accident in 2011, concerns
about radiation exposure and decline in subjective well-being have been reported.
To tackle these problems, various countermeasures in relation to radiation have
been implemented. In this study, we comprehensively evaluated the effects of
radiological countermeasures on subjective well-being (e.g., satisfaction with
life (SWL) and emotional well-being) and radiation anxiety, through a
questionnaire survey targeting Fukushima residents (N = 1023). Propensity scores
matching was applied to evaluate significant effects of radiological
countermeasures on subjective well-being and radiation anxiety. Among the
radiological countermeasures, thyroid examination, whole body counter, and air
dose monitoring showed the highest proportions of participation, utilization, and
useful evaluation, suggesting a high degree of public attention focused on these
countermeasures. The basic survey was associated with significant increases in
SWL and self-rated health (SH). Thyroid examination was significantly associated
with not only a reduction in radiation anxiety but also an increase of emotional
stress, suggesting the importance of careful design of system and detailed
communication. Food inspection was associated with deterioration in SH. Those who
utilized explanatory meetings showed increases in sadness, worry, and radiation
anxiety, indicating that additional attention is required of the experts and
authorities involved in explanatory meetings.
PMID- 29329264
TI - Engineering Ru@Pt Core-Shell Catalysts for Enhanced Electrochemical Oxygen
Reduction Mass Activity and Stability.
AB - Improving the performance of oxygen reduction reaction (ORR) electrocatalysts is
essential for the commercial efficacy of many renewable energy technologies,
including low temperature polymer electrolyte fuel cells (PEFCs). Herein, we
report highly active and stable carbon-supported Ru@Pt core-shell nanoparticles
(Ru@Pt/C) prepared by a wet chemical synthesis technique. Through rotating disc
electrode testing, the Ru@Pt/C achieves an ORR Pt mass-based activity of 0.50 A
mgPt-1 at 0.9 V versus the reversible hydrogen electrode (RHE), which exceeds the
activity of the state-of-the-art commercial Pt/C catalyst as well as the
Department of Energy 2020 PEFC electrocatalyst activity targets for
transportation applications. The impact of various synthetic parameters,
including Pt to Ru ratios and catalyst pretreatments (i.e., annealing) are
thoroughly explored. Pt-based mass activity of all prepared Ru@Pt/C catalysts was
found to exceed 0.4 mgPt-1 across the range of compositions investigated, with
the maximum activity catalyst having a Ru:Pt ratio of 1:1. This optimized
composition of Ru@Pt/C catalyst demonstrated remarkable stability after 30,000
accelerated durability cycles (0.6 to 1.0 V vs. RHE at 125 mV s-1), maintaining
85% of its initial mass activity. Scanning transmission electron microscopy
energy dispersive spectroscopy (STEM-EDS) analysis at various stages of
electrochemical testing demonstrated that the Pt shell can provide sufficient
protection against the dissolution of the otherwise unstable Ru core.
PMID- 29329265
TI - Multiple-Octave-Spanning Vibration Sensing Based on Simultaneous Vector
Demodulation of 499 Fizeau Interference Signals from Identical Ultra-Weak Fiber
Bragg Gratings Over 2.5 km.
AB - Multi-point vibration sensing at the low frequency range of 0.5-100 Hz is of
vital importance for applications such as seismic monitoring and underwater
acoustic imaging. Location-resolved multi-point sensing using a single fiber and
a single demodulation system can greatly reduce system deployment and maintenance
costs. We propose and demonstrate the demodulation of a fiber-optic system
consisting of 500 identical ultra-weak Fiber Bragg gratings (uwFBGs), capable of
measuring the amplitude, frequency and phase of acoustic signals from 499 sensing
fibers covering a total range of 2.5 km. For demonstration purposes, we
arbitrarily chose six consecutive sensors and studied their performance in
detail. Using a passive demodulation method, we interrogated the six sensors
simultaneously, and achieved a high signal-to-noise ratio of 22.1 dB, excellent
linearity, phase sensitivity of around 0.024 rad/Pa, and a dynamic range of about
38 dB. We demonstrated a frequency response flatness of <1.2 dB in the range of
0.5-100 Hz. Compared to the prior state-of-the-art demonstration using a similar
method, we have increased the sensing range from 1 km to 2.5 km, and increased
the frequency range from 0.4 octaves to 7.6 octaves, in addition to achieving
sensing in the very challenging low-frequency range of 0.5-100 Hz.
PMID- 29329266
TI - Relative Validity of a 24-h Recall in Assessing Intake of Key Nutrients in a
Cohort of Australian Toddlers.
AB - There is limited information concerning the dietary intake of toddlers in
Australia. Consequently, there is a need for studies investigating toddler intake
that use dietary assessment measures that are valid and place a low participant
burden on caregivers. The aim of this study was to determine the relative
validity of a single 24-h dietary recall (24HR) in measuring the intake of five
nutrients in a cohort of Australian toddlers compared to a combined 24HR and 2
day estimated food record (2DFR). A single 24HR and a 2DFR were collected from a
cohort of Australian toddlers (n = 699) at approximately 12 months of age as part
of the Study of Mothers' and Infants' Life Events affecting oral health (SMILE)
project. Relative validity of one day of dietary data (24HR) in assessing intake
of energy, protein, calcium, iron, and added sugars was tested against three days
of dietary data (24HR + 2DFR) using paired t-tests, Bland-Altman analysis, cross
classification, and weighted Kappa statistic. Classification analysis found good
agreement between the 24HR and 24HR + 2DFR for all nutrients with the percentage
classified in the same tertile at 57.9% and above. The weighted Kappa statistic
found acceptable agreement for all nutrients. This study suggests that a 24HR is
a valid assessment tool for estimating the relative intake of energy, protein,
calcium, iron, and added sugars among Australian toddlers at the individual
level.
PMID- 29329267
TI - A Mild Aqueous Sonogashira Reaction as a Fluorescent Labeling Strategy for 5
Bromide-2'-Deoxyuridine.
AB - C5-modified uridines are a valuable class of nucleoside analogues, both as potent
chemotherapy agents and through their use as the conjunction site in DNA labeling
strategies. As an important C5-modified uridine, BrdU has been used in cell
proliferation assays since the 1980s. Currently, the detection of BrdU relies on
traditional immunostaining; however, this approach has its limitations. Thus, it
is desirable, albeit difficult, to develop chemistry methods to fluorescently
label BrdU in a cellular context. In the present study, we report our efforts
toward developing a robust chemistry methodology for BrdU fluorescent labeling.
The Sonogashira reaction was chosen as the key reaction, and various alkynyl
groups (aliphatic or aryl) containing fluorescent dyes were synthesized to cross
couple with BrdU. Various bases and catalyst systems were screened to evaluate
the optimum conditions. A mild aqueous Sonogashira reaction (K2PdCl4, S-Phos, n
Bu4N+OH-, Sodium d-isoascorbate, EtOH/H2O = 1:1, 37 degrees C, Ar) was obtained
to enable high-yielding BrdU fluorescent labeling.
PMID- 29329268
TI - Anomaly Detection in Nanofibrous Materials by CNN-Based Self-Similarity.
AB - Automatic detection and localization of anomalies in nanofibrous materials help
to reduce the cost of the production process and the time of the post-production
visual inspection process. Amongst all the monitoring methods, those exploiting
Scanning Electron Microscope (SEM) imaging are the most effective. In this paper,
we propose a region-based method for the detection and localization of anomalies
in SEM images, based on Convolutional Neural Networks (CNNs) and self-similarity.
The method evaluates the degree of abnormality of each subregion of an image
under consideration by computing a CNN-based visual similarity with respect to a
dictionary of anomaly-free subregions belonging to a training set. The proposed
method outperforms the state of the art.
PMID- 29329269
TI - Design, Synthesis, and Safener Activity of Novel Methyl (R)-N
Benzoyl/Dichloroacetyl-Thiazolidine-4-Carboxylates.
AB - A series of novel methyl (R)-N-benzoyl/dichloroacetyl-thiazolidine-4-carboxylates
were designed by active substructure combination. The title compounds were
synthesized using a one-pot route from l-cysteine methyl ester hydrochloride,
acyl chloride, and ketones. All compounds were characterized by IR, 1H NMR, 13C
NMR, and HRMS. The structure of 4q was determined by X-ray crystallography. The
biological tests showed that the title compounds protected maize from chlorimuron
ethyl injury to some extent. The ALS activity assay showed that the title
compounds increased the ALS activity of maize inhibited by chlorimuron-ethyl.
Molecular docking modeling demonstrated that Compound 4e competed against
chlorimuron-ethyl to combine with the herbicide target enzyme active site,
causing the herbicide to be ineffective.
PMID- 29329270
TI - Toxicity Evaluation of Individual and Mixtures of Nanoparticles Based on Algal
Chlorophyll Content and Cell Count.
AB - The toxic effects of individual and binary mixtures of five metal oxide
nanoparticles (NPs) were evaluated based on changes in two endpoints of algal
growth: the cell count and chlorophyll content. Various effects were observed
according to the concentration tested and type of NPs, and there were no
significant differences in findings for the two endpoints. In general, ZnO NPs
caused the greatest inhibition of algal growth, and Fe2O3 NPs the least. The EC50
for ZnO was 2.0 mg/L for the cell count and 2.6 mg/L for the chlorophyll content,
and it was 76 and 90 mg/L, respectively, for Fe2O3. The EC50 values were in the
order ZnO > NiO > CuO > TiO2 > Fe2O3. Subsequently, the effects of 30 binary
mixture combinations on the chlorophyll content were evaluated. Comparisons were
made between the observed and the expected toxicities calculated based on the
individual NP toxicities. Overall, additive action (67%) was mainly observed,
followed by antagonistic (16.5%) and synergistic (16.5%) actions. These results
suggest that environmental exposure to NP mixtures may cause toxicity levels
similar to the sum of those of the constituent NPs.
PMID- 29329271
TI - Transketolase Is Identified as a Target of Herbicidal Substance alpha-Terthienyl
by Proteomics.
AB - alpha-terthienyl is a natural phytotoxin isolated originally from Flaveria
bidentis (L.) Kuntze. The bioassay presented here shows the strong herbicidal
activity of alpha-terthienyl on Digitaria sanguinalis, Arabidopsis thaliana and
Chlamydomonas reinhardtii. The alpha-terthienyl-induced response of A. thaliana
at the protein level was analyzed at different times. Changes in the protein
expression profiles were analyzed by two-dimensional gel electrophoresis and
liquid chromatography tandem mass spectrometry (LC-MS/MS) mass spectrometry.
Sixteen protein spots were identified that showed reproducible changes in the
expression of at least 2-fold when compared to the control. Among these 16 spots,
three were up-regulated and 13 were down-regulated. The decreased expression of
several proteins associated with energy production and carbon metabolism
suggested that these processes were affected by alpha-terthienyl. To search for
the candidate proteins in this screen, A. thaliana T-DNA mutants of the candidate
proteins were used to test their susceptibility to alpha-terthienyl. Amongst the
others, attkl1, a mutant of transketolase, exhibited a significantly lower
sensitivity to alpha-terthienyl when hit compared with Col-0. Based on the
identification of the proteins associated with the response to alpha-terthienyl
by proteomics, a candidate target protein transketolase was identified.
PMID- 29329272
TI - Rapid Screening and Identification of Daidzein Metabolites in Rats Based on UHPLC
LTQ-Orbitrap Mass Spectrometry Coupled with Data-Mining Technologies.
AB - Daidzein, the main bioactive soy isoflavone in Nature, has been found to possess
many biological functions. It has been investigated in particular as a
phytoestrogen owing to the similarity of its structure with that of the human
hormone estrogen. Due to the lack of comprehensive studies on daidzein
metabolism, further research is still required to clarify its in vivo metabolic
fate and intermediate processes. In this study, an efficient strategy was
established using UHPLC-LTQ-Orbitrap mass spectrometry to profile the metabolism
of daidzein in rats. Meanwhile, multiple data-mining methods including high
resolution extracted ion chromatogram (HREIC), multiple mass defect filtering
(MMDF), neutral loss fragment (NLF), and diagnostic product ion (DPI) were
utilized to investigate daidzein metabolites from the HR-ESI-MS1 to ESI-MSn stage
in both positive and negative ion modes. Consequently, 59 metabolites, including
prototype compounds, were positively or tentatively elucidated based on reference
standards, accurate mass measurements, mass fragmentation behaviors,
chromatographic retention times, and corresponding calculated ClogP values. As a
result, dehydration, hydrogenation, methylation, dimethylation, glucuronidation,
glucosylation, sulfonation, ring-cleavage, and their composite reactions were
ascertained to interpret its in vivo biotransformation. Overall, our results not
only revealed the potential pharmacodynamics forms of daidzein, but also aid in
establishing a practical strategy for rapid screening and identifying metabolites
of natural compounds.
PMID- 29329273
TI - Transcriptomics Evidence for Common Pathways in Human Major Depressive Disorder
and Glioblastoma.
AB - Depression as a common complication of brain tumors. Is there a possible common
pathogenesis for depression and glioma? The most serious major depressive
disorder (MDD) and glioblastoma (GBM) in both diseases are studied, to explore
the common pathogenesis between the two diseases. In this article, we first rely
on transcriptome data to obtain reliable and useful differentially expressed
genes (DEGs) by differential expression analysis. Then, we used the
transcriptomics of DEGs to find out and analyze the common pathway of MDD and GBM
from three directions. Finally, we determine the important biological pathways
that are common to MDD and GBM by statistical knowledge. Our findings provide the
first direct transcriptomic evidence that common pathway in two diseases for the
common pathogenesis of the human MDD and GBM. Our results provide a new reference
methods and values for the study of the pathogenesis of depression and
glioblastoma.
PMID- 29329275
TI - Chitosan-Starch Films with Natural Extracts: Physical, Chemical, Morphological
and Thermal Properties.
AB - The aim of this study is to analyze the properties of a series of polysaccharide
composite films, such as apparent density, color, the presence of functional
groups, morphology, and thermal stability, as well as the correlation between
them and their antimicrobial and optical properties. Natural antioxidants such as
anthocyanins (from cranberry; blueberry and pomegranate); betalains (from
beetroot and pitaya); resveratrol (from grape); and thymol and carvacrol (from
oregano) were added to the films. Few changes in the position and intensity of
the FTIR spectra bands were observed despite the low content of extract added to
the films. Due to this fact, the antioxidants were extracted and identified by
spectroscopic analysis; and they were also quantified using the Folin-Denis
method and a gallic acid calibration curve, which confirmed the presence of
natural antioxidants in the films. According to the SEM analysis, the presence of
natural antioxidants has no influence on the film morphology because the stretch
marks and white points that were observed were related to starch presence. On the
other hand, the TGA analysis showed that the type of extract influences the total
weight loss. The overall interpretation of the results suggests that the use of
natural antioxidants as additives for chitosan-starch film preparation has a
prominent impact on most of the critical properties that are decisive in making
them suitable for food-packing applications.
PMID- 29329274
TI - Current Technologies of Electrochemical Immunosensors: Perspective on Signal
Amplification.
AB - An electrochemical immunosensor employs antibodies as capture and detection means
to produce electrical charges for the quantitative analysis of target molecules.
This sensor type can be utilized as a miniaturized device for the detection of
point-of-care testing (POCT). Achieving high-performance analysis regarding
sensitivity has been one of the key issues with developing this type of biosensor
system. Many modern nanotechnology efforts allowed for the development of
innovative electrochemical biosensors with high sensitivity by employing various
nanomaterials that facilitate the electron transfer and carrying capacity of
signal tracers in combination with surface modification and bioconjugation
techniques. In this review, we introduce novel nanomaterials (e.g., carbon
nanotube, graphene, indium tin oxide, nanowire and metallic nanoparticles) in
order to construct a high-performance electrode. Also, we describe how to
increase the number of signal tracers by employing nanomaterials as carriers and
making the polymeric enzyme complex associated with redox cycling for signal
amplification. The pros and cons of each method are considered throughout this
review. We expect that these reviewed strategies for signal enhancement will be
applied to the next versions of lateral-flow paper chromatography and
microfluidic immunosensor, which are considered the most practical POCT biosensor
platforms.
PMID- 29329277
TI - Synthesis, Structural Characterization, Antimicrobial Activity, and In Vitro
Biocompatibility of New Unsaturated Carboxylate Complexes with 2,2'-Bipyridine.
AB - The synthesis, structural characterization, cytotoxicity, and antimicrobial
properties of four new complexes formed by employing acrylate anion and 2,2'
bipyridine are reported herein. X-ray crystallography revealed the trinuclear
nature of [Mn3(2,2'-bipy)2(C3H3O2)6] (1), meanwhile complexes with general
formula [M(2,2'-bipy)(C3H3O2)2(H2O)x]?yH2O ((2) M: Ni, x = 1, y = 0; (3) M: Cu, x
= 1, y = 0; (4) M: Zn, x = 0, y = 1; 2,2'-bipy: 2,2'-bipyridine; C3H3O2: acrylate
anion) were shown to be mononuclear. The lowest minimum inhibitory concentration
(MIC) of 128 MUg mL-1 was recorded for all four tested complexes against Candida
albicans, for complex (3) against Escherichia coli, and for complex (4) against
Staphylocococcus aureus. Compounds (3) and (4) were also potent efflux pumps
activity inhibitors (EPI), proving their potential for use in synergistic
combinations with antibiotics. Complexes (1)-(4) revealed that they were not
cytotoxic to HCT-8 cells. They also proved to interfere with the cellular cycle
of tumour HCT-8 cells by increasing the number of cells found in the S and G2/M
phases. Taken together, these results demonstrate the potential of zinc and
copper complexes for use in the development of novel antimicrobial and anti
proliferative agents.
PMID- 29329276
TI - The Safety of the Neighborhood Environment and Physical Activity in Czech and
Polish Adolescents.
AB - (1) Background: An increase in or at least the sustainment of walking activities
across a wide section of the population is a crucial health-related task for
Central and East European countries. The aim of this study was to assess the
associations between adolescents' walking activities and various levels of
perceived safety of the built environment in differing socio-demographic
backgrounds of Poland and the Czech Republic. Furthermore, we aimed to determine
major moderators affecting the walking habits of adolescents in areas with
different levels of walkability. (2) Methods: The surveys were conducted during
the 2008-2009 and 2013-2014 school years in 24 Polish and 35 Czech secondary
schools, with a sample of 2001 adolescents. All participants completed the
International Physical Activity Questionnaire-Long Form and the NEWS-Abbreviated.
Selected students took part in objective weekly monitoring of physical activity
(PA). (3) Results: Boys and girls who perceived their neighborhood environment as
the safest were significantly more likely to meet the recommendations for leisure
time walking. Adolescents from the safest environment achieved 11,024 steps/day
on average, while those from the least safe environment achieved 9686 steps/day.
(4) Conclusions: A safe neighborhood environment significantly predicts walking
activities among girls. Environmental safety improvement can support the active
transport and better use of leisure time PA.
PMID- 29329278
TI - T-DNA Tagging-Based Gain-of-Function of OsHKT1;4 Reinforces Na Exclusion from
Leaves and Stems but Triggers Na Toxicity in Roots of Rice Under Salt Stress.
AB - The high affinity K+ transporter 1;4 (HKT1;4) in rice (Oryza sativa), which shows
Na+ selective transport with little K+ transport activity, has been suggested to
be involved in reducing Na in leaves and stems under salt stress. However,
detailed physiological roles of OsHKT1;4 remain unknown. Here, we have
characterized a transfer DNA (T-DNA) insertion mutant line of rice, which
overexpresses OsHKT1;4, owing to enhancer elements in the T-DNA, to gain an
insight into the impact of OsHKT1;4 on salt tolerance of rice. The homozygous
mutant (the O/E line) accumulated significantly lower concentrations of Na in
young leaves, stems, and seeds than the sibling WT line under salt stress.
Interestingly, however, the mutation rendered the O/E plants more salt sensitive
than WT plants. Together with the evaluation of biomass of rice lines,
rhizosphere acidification assays using a pH indicator bromocresol purple and
22NaCl tracer experiments have led to an assumption that roots of O/E plants
suffered heavier damages from Na which excessively accumulated in the root due to
increased activity of Na+ uptake and Na+ exclusion in the vasculature.
Implications toward the application of the HKT1-mediated Na+ exclusion system to
the breeding of salt tolerant crop cultivars will be discussed.
PMID- 29329279
TI - Diosgenin Protects Rats from Myocardial Inflammatory Injury Induced by Ischemia
Reperfusion.
AB - BACKGROUND Diosgenin, a phytosteroid sapogenin, has anti-inflammatory properties
shown to reduce myocardial ischemia-reperfusion injury (MIRI). However, the
specific mechanism by which this is achieved is not clear. This study
investigated the protective effects of diosgenin on myocardial
ischemia/reperfusion (I/R) and the potential anti-inflammatory mechanisms.
MATERIAL AND METHODS Healthy adult male SD rats, body weight (b.w.) 250-280 g,
were used to model ischemia-reperfusion injury (IRI) and were administered
diosgenin (50 mg/kg and 100 mg/kg b.w.) intragastrically for 4 consecutive weeks
before surgery. The left anterior descending artery (LAD) was ligated to induce
myocardial ischemia for 30 min and reperfusion for 30 min, 60 min, and 120 min
while relevant indicators were detected. RESULTS Both 50 mg and 100 mg diosgenin
oral administration increased left ventricular developed pressure (LVDP) and
maximum changing rate of ventricular pressure (+/-dp/dtmax), decreased left
ventricular end-diastolic pressure (LVEDP), and myocardial enzyme markers. TTC
staining suggested that diosgenin reduced myocardial infarct size in the rat
model. Pathological results showed that myocardial ischemia and inflammation were
alleviated by diosgenin. In addition, the increased expression of tumor necrosis
factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta) in serum, and
myeloperoxidase (MPO) in myocardium were significantly suppressed by diosgenin
administration. Diosgenin further inhibited the phosphorylation of transcription
factor NF-kappaB and modulated the expression of downstream inflammatory
cytokines by regulating the activation of p38-MAPK and JNK pathways. CONCLUSIONS
Results demonstrate diosgenin plays an anti-inflammatory role in the protection
of MIRI through regulation of p38-MAPK and JNK pathways and phosphorylation of NF
kappaB.
PMID- 29329281
TI - Early career investigator highlight: April.
PMID- 29329280
TI - Status of HIV Epidemic Control Among Adolescent Girls and Young Women Aged 15-24
Years - Seven African Countries, 2015-2017.
AB - In 2016, an estimated 1.5 million females aged 15-24 years were living with human
immunodeficiency virus (HIV) infection in Eastern and Southern Africa, where the
prevalence of HIV infection among adolescent girls and young women (3.4%) is more
than double that for males in the same age range (1.6%) (1). Progress was
assessed toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 2020
targets for adolescent girls and young women in sub-Saharan Africa (90% of those
with HIV infection aware of their status, 90% of HIV-infected persons aware of
their status on antiretroviral treatment [ART], and 90% of those on treatment
virally suppressed [HIV viral load <1,000 HIV RNA copies/mL]) (2) using data from
recent Population-based HIV Impact Assessment (PHIA) surveys in seven countries.
The national prevalence of HIV infection in adolescent girls and young women aged
15-24 years, the percentage who were aware of their status, and among those
persons who were aware, the percentage who had achieved viral suppression were
calculated. The target for viral suppression among all persons with HIV infection
is 73% (the product of 90% x 90% x 90%). Among all seven countries, the
prevalence of HIV infection among adolescent girls and young women was 3.6%;
among those in this group, 46.3% reported being aware of their HIV-positive
status, and 45.0% were virally suppressed. Sustained efforts by national HIV and
public health programs to diagnose HIV infection in adolescent girls and young
women as early as possible to ensure rapid initiation of ART should help achieve
epidemic control among adolescent girls and young women.
PMID- 29329282
TI - Induction of high-mobility group Box-1 in vitro and in vivo by respiratory
syncytial virus.
AB - BackgroundDespite decades that have passed since its discovery, accurate
biomarkers of respiratory syncytial virus (RSV) disease activity and effective
therapeutic strategies are still lacking. The high-mobility group box type 1
(HMGB1) protein has been proposed as a possible link between RSV and immune
system, but only limited information is currently available to support this
hypothesis.MethodsExpression of HMGB1 gene and protein was analyzed by
quantitative PCR, enzyme-linked immunosorbent assay (ELISA), western blot,
immunocytochemistry, and confocal microscopy in immortalized and primary human
bronchial epithelial cells, as well as in rat pup lungs. The role of HMGB1 in RSV
infection was explored using glycyrrhizin, a selective HMGB1 inhibitor.ResultsRSV
infection strongly induced HMGB1 expression both in vitro and in vivo.
Glycyrrhizin dose-dependently inhibited HMGB1 upregulation in both RSV-infected
immortalized and primary human bronchial epithelial cells, and this effect was
associated with significant reduction of viral replication.ConclusionOur data
suggest that HMGB1 expression increases during RSV replication. This seems to
have a critical pathogenic role as its selective inhibition virtually modified
the infection. These observations provide further insight into the
pathophysiology of RSV infection and uncover a potential biomarker and
therapeutic target for the most common respiratory infection of infancy.
PMID- 29329283
TI - Modeling the assembly order of multimeric heteroprotein complexes.
AB - Protein-protein interactions are the cornerstone of numerous biological
processes. Although an increasing number of protein complex structures have been
determined using experimental methods, relatively fewer studies have been
performed to determine the assembly order of complexes. In addition to the
insights into the molecular mechanisms of biological function provided by the
structure of a complex, knowing the assembly order is important for understanding
the process of complex formation. Assembly order is also practically useful for
constructing subcomplexes as a step toward solving the entire complex
experimentally, designing artificial protein complexes, and developing drugs that
interrupt a critical step in the complex assembly. There are several experimental
methods for determining the assembly order of complexes; however, these
techniques are resource-intensive. Here, we present a computational method that
predicts the assembly order of protein complexes by building the complex
structure. The method, named Path-LzerD, uses a multimeric protein docking
algorithm that assembles a protein complex structure from individual subunit
structures and predicts assembly order by observing the simulated assembly
process of the complex. Benchmarked on a dataset of complexes with experimental
evidence of assembly order, Path-LZerD was successful in predicting the assembly
pathway for the majority of the cases. Moreover, when compared with a simple
approach that infers the assembly path from the buried surface area of subunits
in the native complex, Path-LZerD has the strong advantage that it can be used
for cases where the complex structure is not known. The path prediction accuracy
decreased when starting from unbound monomers, particularly for larger complexes
of five or more subunits, for which only a part of the assembly path was
correctly identified. As the first method of its kind, Path-LZerD opens a new
area of computational protein structure modeling and will be an indispensable
approach for studying protein complexes.
PMID- 29329284
TI - Identification of an elaborate NK-specific system regulating HLA-C expression.
AB - The HLA-C gene appears to have evolved in higher primates to serve as a dominant
source of ligands for the KIR2D family of inhibitory MHC class I receptors. The
expression of NK cell-intrinsic MHC class I has been shown to regulate the murine
Ly49 family of MHC class I receptors due to the interaction of these receptors
with NK cell MHC in cis. However, cis interactions have not been demonstrated for
the human KIR and HLA proteins. We report the discovery of an elaborate NK cell
specific system regulating HLA-C expression, indicating an important role for HLA
C in the development and function of NK cells. A large array of alternative
transcripts with differences in intron/exon content are generated from an
upstream NK-specific HLA-C promoter, and exon content varies between HLA-C
alleles due to SNPs in splice donor/acceptor sites. Skipping of the first coding
exon of HLA-C generates a subset of untranslatable mRNAs, and the proportion of
untranslatable HLA-C mRNA decreases as NK cells mature, correlating with
increased protein expression by mature NK cells. Polymorphism in a key Ets
binding site of the NK promoter has generated HLA-C alleles that lack significant
promoter activity, resulting in reduced HLA-C expression and increased functional
activity. The NK-intrinsic regulation of HLA-C thus represents a novel mechanism
controlling the lytic activity of NK cells during development.
PMID- 29329285
TI - A direct interaction of cholesterol with the dopamine transporter prevents its
out-to-inward transition.
AB - Monoamine transporters (MATs) carry out neurotransmitter reuptake from the
synaptic cleft, a key step in neurotransmission, which is targeted in the
treatment of neurological disorders. Cholesterol (CHOL), a major component of the
synaptic plasma membrane, has been shown to exhibit a modulatory effect on MATs.
Recent crystal structures of the dopamine transporter (DAT) revealed the presence
of two conserved CHOL-like molecules, suggesting a functional protein-CHOL direct
interaction. Here, we present extensive atomistic molecular dynamics (MD)
simulations of DAT in an outward-facing conformation. In the absence of bound
CHOL, DAT undergoes structural changes reflecting early events of dopamine
transport: transition to an inward-facing conformation. In contrast, in the
presence of bound CHOL, these conformational changes are inhibited, seemingly by
an immobilization of the intracellular interface of transmembrane helix 1a and 5
by CHOL. We also provide evidence, from coarse grain MD simulations that the CHOL
sites observed in the DAT crystal structures are preserved in all human monoamine
transporters (dopamine, serotonin and norepinephrine), suggesting that our
findings might extend to the entire family.
PMID- 29329286
TI - Is the proportional recovery rule applicable to the lower limb after a first-ever
ischemic stroke?
AB - OBJECTIVE: To investigate (a) the applicability of the proportional recovery rule
of spontaneous neurobiological recovery to motor function of the paretic lower
extremity (LE); and (b) the presence of fitters and non-fitters of this
prognostic rule poststroke. When present, the clinical threshold for fitting nor
non-fitting would be determined, as well as within-subject generalizability to
the paretic upper extremity (UE). METHODS: Prospective cohort study in which the
Fugl-Meyer Assessment (FMA)-LE and FMA-UE were measured <72 hours and 6 months
poststroke. Predicted maximum potential recovery was defined as [FMA-LEmax-FMA
LEinitial = 34 -FMA-LEinitial]. Hierarchical clustering in 202 first-ever
ischemic stroke patients distinguished between fitting and not fitting the rule.
Descriptive statistics determined whether fitters and non-fitters for LE were the
same persons as for UE. RESULTS: 175 (87%) patients fitted the FMA-LE recovery
rule. The observed average improvement of the fitters was ~64% of the predicted
maximum potential recovery. In the non-fitter group, the maximum initial FMA-LE
score was 13 points. Fifty-one out of 78 patients (~65%) who scored below the
identified 14-point threshold at baseline fitted the FMA-LE rule. Non-fitters
were more severely affected than fitters. All non-fitters of the FMA-LE rule did
also not fit the proportional recovery rule for FMA-UE. CONCLUSIONS: Proportional
recovery seems to be consistent within subjects across LE and UE motor impairment
at the hemiplegic side in first-ever ischemic hemispheric stroke subjects. Future
studies should investigate prospectively distinguishing between fitters and not
fitters within the subgroup of patients who have initial low FMA-LE scores.
Subsequently, patients could be stratified based on fitting or not fitting the
recovery rule as this would impact rehabilitation management and trial design.
PMID- 29329287
TI - Isolation and complete genome analysis of neurotropic dengue virus serotype 3
from the cerebrospinal fluid of an encephalitis patient.
AB - Although neurological manifestations associated with dengue viruses (DENV)
infection have been reported, there is very limited information on the genetic
characteristics of neurotropic DENV. Here we describe the isolation and complete
genome analysis of DENV serotype 3 (DENV-3) from cerebrospinal fluid of an
encephalitis paediatric patient in Jakarta, Indonesia. Next-generation sequencing
was employed to deduce the complete genome of the neurotropic DENV-3 isolate.
Based on complete genome analysis, two unique and nine uncommon amino acid
changes in the protein coding region were observed in the virus. A phylogenetic
tree and molecular clock analysis revealed that the neurotropic virus was a
member of Sumatran-Javan clade of DENV-3 genotype I and shared a common ancestor
with other isolates from Jakarta around 1998. This is the first report of
neurotropic DENV-3 complete genome analysis, providing detailed information on
the genetic characteristics of this virus.
PMID- 29329288
TI - Soil-transmitted helminth infection, loss of education and cognitive impairment
in school-aged children: A systematic review and meta-analysis.
AB - BACKGROUND: Evidence of an adverse influence of soil transmitted helminth (STH)
infections on cognitive function and educational loss is equivocal. Prior meta
analyses have focused on randomized controlled trials only and have not
sufficiently explored the potential for disparate influence of STH infection by
cognitive domain. We re-examine the hypothesis that STH infection is associated
with cognitive deficit and educational loss using data from all primary
epidemiologic studies published between 1992 and 2016. METHODS: Medline, Biosis
and Web of Science were searched for original studies published in the English
language. Cognitive function was defined in four domains (learning, memory,
reaction time and innate intelligence) and educational loss in two domains
(attendance and scholastic achievement). Pooled effect across studies were
calculated as standardized mean differences (SMD) to compare cognitive and
educational measures for STH infected/non-dewormed children versus STH uninfected
/dewormed children using Review Manager 5.3. Sub-group analyses were implemented
by study design, risk of bias (ROB) and co-prevalence of Schistosoma species
infection. Influential studies were excluded in sensitivity analysis to examine
stability of pooled estimates. FINDINGS: We included 36 studies of 12,920
children. STH infected/non-dewormed children had small to moderate deficits in
three domains-learning, memory and intelligence (SMD: -0.44 to -0.27, P<0.01
0.03) compared to STH-uninfected/dewormed children. There were no differences by
infection/treatment status for reaction time, school attendance and scholastic
achievement (SMD: -0.26 to -0.16, P = 0.06-0.19). Heterogeneity of the pooled
effects in all six domains was high (P<0.01; I2 = 66-99%). Application of outlier
treatment reduced heterogeneity in learning domain (P = 0.12; I2 = 33%) and
strengthened STH-related associations in all domains but intelligence (SMD:
0.20, P = 0.09). Results varied by study design and ROB. Among experimental
intervention studies, there was no association between STH treatment and
educational loss/performance in tests of memory, reaction time and innate
intelligence (SMD: -0.27 to 0.17, P = 0.18-0.69). Infection-related deficits in
learning persisted within design/ROB levels (SMD: -0.37 to -52, P<0.01) except
for pre-vs post intervention design (n = 3 studies, SMD = -0.43, P = 0.47).
Deficits in memory, reaction time and innate intelligence persisted within
observational studies (SMD: -0.23 to -0.38, all P<0.01) and high ROB strata (SMD:
0.37 to -0.83, P = 0.07 to <0.01). Further, in Schistosoma infection co-prevalent
settings, associations were generally stronger and statistically robust for STH
related deficits in learning, memory and reaction time tests(SMD:-0.36 to -0.55,
P = 0.003-0.02). STH-related deficits in school attendance and scholastic
achievement was noted in low (SMD:-0.57, P = 0.05) and high ROB strata
respectively. INTERPRETATION: We provide evidence of superior performance in five
of six educational and cognitive domains assessed for STH uninfected/dewormed
versus STH infected/not-dewormed school-aged children from helminth endemic
regions. Cautious interpretation is warranted due to high ROB in some of the
primary literature and high between study variability in most domains.
Notwithstanding, this synthesis provides empirical support for a cognitive and
educational benefit of deworming. The benefit of deworming will be enhanced by
strategically employing, integrated interventions. Thus, multi-pronged inter
sectoral strategies that holistically address the environmental and structural
roots of child cognitive impairment and educational loss in the developing world
may be needed to fully realize the benefit of mass deworming programs.
PMID- 29329289
TI - Burkholderia pseudomallei modulates host iron homeostasis to facilitate iron
availability and intracellular survival.
AB - BACKGROUND: The control over iron homeostasis is critical in host-pathogen
interaction. Iron plays not only multiple roles for bacterial growth and
pathogenicity, but also for modulation of innate immune responses. Hepcidin is a
key regulator of host iron metabolism triggering degradation of the iron exporter
ferroportin. Although iron overload in humans is known to increase susceptibility
to Burkholderia pseudomallei, it is unclear how the pathogen competes with the
host for the metal during infection. This study aimed to investigate whether B.
pseudomallei, the causative agent of melioidosis, modulates iron balance and how
regulation of host cell iron content affects intracellular bacterial
proliferation. PRINCIPAL FINDINGS: Upon infection of primary macrophages with B.
pseudomallei, expression of ferroportin was downregulated resulting in higher
iron availability within macrophages. Exogenous modification of iron export
function by hepcidin or iron supplementation by ferric ammonium citrate led to
increased intracellular iron pool stimulating B. pseudomallei growth, whereas the
iron chelator deferoxamine reduced bacterial survival. Iron-loaded macrophages
exhibited a lower expression of NADPH oxidase, iNOS, lipocalin 2, cytokines and
activation of caspase-1. Infection of mice with the pathogen caused a diminished
hepatic ferroportin expression, higher iron retention in the liver and lower iron
levels in the serum (hypoferremia). In vivo administration of ferric ammonium
citrate tended to promote the bacterial growth and inflammatory response, whereas
limitation of iron availability significantly ameliorated bacterial clearance,
attenuated serum cytokine levels and improved survival of infected mice.
CONCLUSIONS: Our data indicate that modulation of the cellular iron balance is
likely to be a strategy of B. pseudomallei to improve iron acquisition and to
restrict antibacterial immune effector mechanisms and thereby to promote its
intracellular growth. Moreover, we provide evidence that changes in host iron
homeostasis can influence susceptibility to melioidosis, and suggest that iron
chelating drugs might be an additional therapeutic option.
PMID- 29329290
TI - MORC2B is essential for meiotic progression and fertility.
AB - The microrchidia (MORC) family proteins are chromatin-remodelling factors and
function in diverse biological processes such as DNA damage response and
transposon silencing. Here, we report that mouse Morc2b encodes a functional germ
cell-specific member of the MORC protein family. Morc2b arose specifically in the
rodent lineage through retrotransposition of Morc2a during evolution.
Inactivation of Morc2b leads to meiotic arrest and sterility in both sexes.
Morc2b-deficient spermatocytes and oocytes exhibit failures in chromosomal
synapsis, blockades in meiotic recombination, and increased apoptosis. Loss of
MORC2B causes mis-regulated expression of meiosis-specific genes. Furthermore, we
find that MORC2B interacts with MORC2A, its sequence paralogue. Our results
demonstrate that Morc2b, a relatively recent gene, has evolved an essential role
in meiosis and fertility.
PMID- 29329294
TI - A two-stage flow-based intrusion detection model for next-generation networks.
AB - The next-generation network provides state-of-the-art access-independent services
over converged mobile and fixed networks. Security in the converged network
environment is a major challenge. Traditional packet and protocol-based intrusion
detection techniques cannot be used in next-generation networks due to slow
throughput, low accuracy and their inability to inspect encrypted payload. An
alternative solution for protection of next-generation networks is to use network
flow records for detection of malicious activity in the network traffic. The
network flow records are independent of access networks and user applications. In
this paper, we propose a two-stage flow-based intrusion detection system for next
generation networks. The first stage uses an enhanced unsupervised one-class
support vector machine which separates malicious flows from normal network
traffic. The second stage uses a self-organizing map which automatically groups
malicious flows into different alert clusters. We validated the proposed approach
on two flow-based datasets and obtained promising results.
PMID- 29329291
TI - Ovule identity mediated by pre-mRNA processing in Arabidopsis.
AB - Ovules are fundamental for plant reproduction and crop yield as they are the
precursors of seeds. Therefore, ovule specification is a critical developmental
program. In Arabidopsis thaliana, ovule identity is redundantly conferred by the
homeotic D-class genes SHATTERPROOF1 (SHP1), SHP2 and SEEDSTICK (STK),
phylogenetically related to the MADS-domain regulatory gene AGAMOUS (AG),
essential in floral organ specification. Previous studies have shown that the HUA
PEP activity, comprised of a suite of RNA-binding protein (RBP) encoding genes,
regulates AG pre-mRNA processing and thus flower patterning and organ identity.
Here, we report that the HUA-PEP activity additionally governs ovule
morphogenesis. Accordingly, in severe hua-pep backgrounds ovules transform into
flower organ-like structures. These homeotic transformations are most likely due
to the dramatic reduction in SHP1, SHP2 and STK activity. Our molecular and
genome-wide profiling strategies revealed the accumulation of prematurely
terminated transcripts of D-class genes in hua-pep mutants and reduced amounts of
their respective functional messengers, which points to pre-mRNA processing
misregulation as the origin of the ovule developmental defects in such
backgrounds. RNA processing and transcription are coordinated by the RNA
polymerase II (RNAPII) carboxyl-terminal domain (CTD). Our results show that HUA
PEP activity members can interact with the CTD regulator C-TERMINAL DOMAIN
PHOSPHATASE-LIKE1 (CPL1), supporting a co-transcriptional mode of action for the
HUA-PEP activity. Our findings expand the portfolio of reproductive developmental
programs in which HUA-PEP activity participates, and further substantiates the
importance of RNA regulatory mechanisms (pre-mRNA co-transcriptional regulation)
for correct gene expression during plant morphogenesis.
PMID- 29329292
TI - Transcriptome profiling with focus on potential key genes for wing development
and evolution in Megaloprepus caerulatus, the damselfly species with the world's
largest wings.
AB - The evolution, development and coloration of insect wings remains a puzzling
subject in evolutionary research. In basal flying insects such as Odonata,
genomic research regarding bauplan evolution is still rare. Here we focus on the
world's largest odonate species-the "forest giant" Megaloprepus caerulatus, to
explore its potential for looking deeper into the development and evolution of
wings. A recently discovered cryptic species complex in this genus previously
considered monotypic is characterized by morphological differences in wing shape
and color patterns. As a first step toward understanding wing pattern divergence
and pathways involved in adaptation and speciation at the genomic level, we
present a transcriptome profiling of M. caerulatus using RNA-Seq and compare
these data with two other odonate species. The de novo transcriptome assembly
consists of 61,560 high quality transcripts and is approximately 93% complete.
For almost 75% of the identified transcripts a possible function could be
assigned: 48,104 transcripts had a hit to an InterPro protein family or domain,
and 28,653 were mapped to a Gene Ontology term. In particular, we focused on
genes related to wing development and coloration. The comparison with two other
species revealed larva-specific genes and a conserved 'core' set of over 8,000
genes forming orthologous clusters with Ischnura elegans and Ladona fulva. This
transcriptome may provide a first point of reference for future research in
odonates addressing questions surrounding the evolution of wing development, wing
coloration and their role in speciation.
PMID- 29329293
TI - Cognitive deficits and educational loss in children with schistosome infection-A
systematic review and meta-analysis.
AB - BACKGROUND: By means of meta-analysis of information from all relevant
epidemiologic studies, we examined the hypothesis that Schistosoma infection in
school-aged children (SAC) is associated with educational loss and cognitive
deficits. METHODOLOGY/PRINCIPAL FINDINGS: This review was prospectively
registered in the PROSPERO database (CRD42016040052). Medline, Biosis, and Web of
Science were searched for studies published before August 2016 that evaluated
associations between Schistosoma infection and cognitive or educational outcomes.
Cognitive function was defined in four domains-learning, memory, reaction time,
and innate intelligence. Educational outcome measures were defined as attendance
and scholastic achievement. Risk of bias (ROB) was evaluated using the Newcastle
Ottawa quality assessment scale. Standardized mean differences (SMD) and 95%
confidence intervals (CI) were calculated to compare cognitive and educational
measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children.
Sensitivity analyses by study design, ROB, and sequential exclusion of individual
studies were implemented. Thirty studies from 14 countries, including 38,992 SAC
between 5-19 years old, were identified. Compared to uninfected children and
children dewormed with praziquantel, the presence of Schistosoma infection and/or
non-dewormed status was associated with deficits in school attendance (SMD =
0.36, 95%CI: -0.60, -0.12), scholastic achievement (SMD = -0.58, 95%CI: -0.96,
0.20), learning (SMD = -0.39, 95%CI: -0.70, -0.09) and memory (SMD = -0.28,
95%CI: -0.52, -0.04) tests. By contrast, Schistosoma-infected/non-dewormed and
uninfected/dewormed children were similar with respect to performance in tests of
reaction time (SMD = -0.06, 95%CI: -0.42, 0.30) and intelligence (SMD = -0.25,
95%CI: -0.57, 0.06). Schistosoma infection-associated deficits in educational
measures were robust among observational studies, but not among interventional
studies. The significance of infection-associated deficits in scholastic
achievement was sensitive to ROB. Schistosoma infection-related deficits in
learning and memory tests were invariant by ROB and study design.
CONCLUSION/SIGNIFICANCE: Schistosoma infection/non-treatment was significantly
associated with educational, learning, and memory deficits in SAC. Early
treatment of children in Schistosoma-endemic regions could potentially mitigate
these deficits. TRIAL REGISTRATION: ClinicalTrials.gov CRD42016040052.
PMID- 29329295
TI - Novel signature fatty acid profile of the giant manta ray suggests reliance on an
uncharacterised mesopelagic food source low in polyunsaturated fatty acids.
AB - Traditionally, large planktivorous elasmobranchs have been thought to
predominantly feed on surface zooplankton during daytime hours. However, the
recent application of molecular methods to examine long-term assimilated diets,
has revealed that these species likely gain the majority from deeper or demersal
sources. Signature fatty acid analysis (FA) of muscle tissue was used to examine
the assimilated diet of the giant manta ray Mobula birostris, and then compared
with surface zooplankton that was collected during feeding and non-feeding events
at two aggregation sites off mainland Ecuador. The FA profiles of M. birostris
and surface zooplankton were markedly different apart from similar proportions of
arachidonic acid, which suggests daytime surface zooplankton may comprise a small
amount of dietary intake for M. birostris. The FA profile of M. birostris muscle
was found to be depleted in polyunsaturated fatty acids, and instead comprised
high proportions of 18:1omega9 isomers. While 18:1omega9 isomers are not
explicitly considered dietary FAs, they are commonly found in high proportions in
deep-sea organisms, including elasmobranch species. Overall, the FA profile of M.
birostris suggests a diet that is mesopelagic in origin, but many mesopelagic
zooplankton species also vertically migrate, staying deep during the day and
moving to shallower waters at night. Here, signature FA analysis is unable to
resolve the depth at which these putative dietary items were consumed and how
availability of this prey may drive distribution and movements of this large
filter-feeder.
PMID- 29329297
TI - Automated multivariate analysis of multi-sensor data submitted online: Real-time
environmental monitoring.
AB - A pilot study demonstrating real-time environmental monitoring with automated
multivariate analysis of multi-sensor data submitted online has been performed at
the cabled LoVe Ocean Observatory located at 258 m depth 20 km off the coast of
Lofoten-Vesteralen, Norway. The major purpose was efficient monitoring of many
variables simultaneously and early detection of changes and time-trends in the
overall response pattern before changes were evident in individual variables. The
pilot study was performed with 12 sensors from May 16 to August 31, 2015. The
sensors provided data for chlorophyll, turbidity, conductivity, temperature
(three sensors), salinity (calculated from temperature and conductivity), biomass
at three different depth intervals (5-50, 50-120, 120-250 m), and current speed
measured in two directions (east and north) using two sensors covering different
depths with overlap. A total of 88 variables were monitored, 78 from the two
current speed sensors. The time-resolution varied, thus the data had to be
aligned to a common time resolution. After alignment, the data were interpreted
using principal component analysis (PCA). Initially, a calibration model was
established using data from May 16 to July 31. The data on current speed from two
sensors were subject to two separate PCA models and the score vectors from these
two models were combined with the other 10 variables in a multi-block PCA model.
The observations from August were projected on the calibration model
consecutively one at a time and the result was visualized in a score plot.
Automated PCA of multi-sensor data submitted online is illustrated with an
attached time-lapse video covering the relative short time period used in the
pilot study. Methods for statistical validation, and warning and alarm limits are
described. Redundant sensors enable sensor diagnostics and quality assurance. In
a future perspective, the concept may be used in integrated environmental
monitoring.
PMID- 29329296
TI - Identification and in silico analysis of functional SNPs of human TAGAP protein:
A comprehensive study.
AB - Genetic polymorphisms in TAGAP gene have been associated with many diseases
including rheumatoid arthritis, multiple sclerosis and other autoimmune
disorders. Identifying functional SNPs in such disease associated genes is an
uphill task hence before planning larger population study, it is better to
scrutinize putative functional SNPs. In this study we used various computational
approaches to identify nsSNPs which are deleterious to the structure and/or
function of TAGAP protein that might be causing these diseases. Computational
analysis was performed by five different in silico tools including SIFT, PROVEAN,
PolyPhen-2, PhD-SNP and SNPs&GO. The study concludes that mutations of Glycine ->
Glutamic Acid at position 120, Glycine -> Tryptophan at position 141 and Valine
> Methionine at position 151 are major mutations in native TAGAP protein which
might contribute to its malfunction and ultimately causing disease. The study
also proposed 3D structures of native TAGAP protein and its three mutants. Future
studies should consider these nsSNPs as main target mutations in various diseases
involving TAGAP malfunction. This is the first comprehensive study, where TAGAP
gene variants were analyzed using in silico tools hence will be of great help
while considering large scale studies and also in developing precision medicines
for cure of diseases related to these polymorphisms. Furthermore, animal models
of various autoimmune diseases and having these mutations might be of help in
exploring their precise roles.
PMID- 29329298
TI - Single image super-resolution based on approximated Heaviside functions and
iterative refinement.
AB - One method of solving the single-image super-resolution problem is to use
Heaviside functions. This has been done previously by making a binary
classification of image components as "smooth" and "non-smooth", describing these
with approximated Heaviside functions (AHFs), and iteration including l1
regularization. We now introduce a new method in which the binary classification
of image components is extended to different degrees of smoothness and non
smoothness, these components being represented by various classes of AHFs. Taking
into account the sparsity of the non-smooth components, their coefficients are l1
regularized. In addition, to pick up more image details, the new method uses an
iterative refinement for the residuals between the original low-resolution input
and the downsampled resulting image. Experimental results showed that the new
method is superior to the original AHF method and to four other published
methods.
PMID- 29329299
TI - Multi-drug resistant non-typhoidal Salmonella associated with invasive disease in
western Kenya.
AB - Non-typhoidal Salmonella (NTS) is a leading cause of bloodstream infections in
Africa, but the various contributions of host susceptibility versus unique
pathogen virulence factors are unclear. We used data from a population-based
surveillance platform (population ~25,000) between 2007-2014 and NTS genome
sequencing to compare host and pathogen-specific factors between individuals
presenting with NTS bacteremia and those presenting with NTS diarrhea. Salmonella
Typhimurium ST313 and Salmonella Enteritidis ST11 were the most common isolates.
Multi-drug resistant strains of NTS were more commonly isolated from patients
presenting with NTS bacteremia compared to NTS diarrhea. This relationship was
observed in patients under age five [aOR = 15.16, 95% CI (2.84-81.05), P =
0.001], in patients five years and older, [aOR = 6.70 95% CI (2.25-19.89), P =
0.001], in HIV-uninfected patients, [aOR = 21.61, 95% CI (2.53-185.0), P =
0.005], and in patients infected with Salmonella serogroup B [aOR = 5.96, 95% CI
(2.28-15.56), P < 0.001] and serogroup D [aOR = 14.15, 95% CI (1.10-182.7), P =
0.042]. Thus, multi-drug-resistant NTS was strongly associated with bacteremia
compared to diarrhea among children and adults. This association was seen in HIV
uninfected individuals infected with either S. Typhimurium or S. Enteritidis.
Risk of developing bacteremia from NTS infection may be driven by virulence
properties of the Salmonella pathogen.
PMID- 29329300
TI - Symmetric dimeric bisbenzimidazoles DBP(n) reduce methylation of RARB and PTEN
while significantly increase methylation of rRNA genes in MCF-7 cancer cells.
AB - BACKGROUND: Hypermethylation is observed in the promoter regions of suppressor
genes in the tumor cancer cells. Reactivation of these genes by demethylation of
their promoters is a prospective strategy of the anticancer therapy. Previous
experiments have shown that symmetric dimeric bisbenzimidazoles DBP(n) are able
to block DNA methyltransferase activities. It was also found that DBP(n) produces
a moderate effect on the activation of total gene expression in HeLa-TI
population containing epigenetically repressed avian sarcoma genome. PRINCIPAL
FINDINGS: It is shown that DBP(n) are able to penetrate the cellular membranes
and accumulate in breast carcinoma cell MCF-7, mainly in the mitochondria and in
the nucleus, excluding the nucleolus. The DBP(n) are non-toxic to the cells and
have a weak overall demethylation effect on genomic DNA. DBP(n) demethylate the
promoter regions of the tumor suppressor genes PTEN and RARB. DBP(n) promotes
expression of the genes RARB, PTEN, CDKN2A, RUNX3, Apaf-1 and APC "silent" in the
MCF-7 because of the hypermethylation of their promoter regions. Simultaneously
with the demethylation of the DNA in the nucleus a significant increase in the
methylation level of rRNA genes in the nucleolus was detected. Increased rDNA
methylation correlated with a reduction of the rRNA amount in the cells by 20
30%. It is assumed that during DNA methyltransferase activity inhibition by the
DBP(n) in the nucleus, the enzyme is sequestered in the nucleolus and provides
additional methylation of the rDNA that are not shielded by DBP(n).
CONCLUSIONS/SIGNIFICANCE: It is concluded that DBP (n) are able to accumulate in
the nucleus (excluding the nucleolus area) and in the mitochondria of cancer
cells, reducing mitochondrial potential. The DBP (n) induce the demethylation of
a cancer cell's genome, including the demethylation of the promoters of tumor
suppressor genes. DBP (n) significantly increase the methylation of ribosomal RNA
genes in the nucleoli. Therefore the further study of these compounds is needed;
it could lead to the creation of new anticancer agents.
PMID- 29329301
TI - Estimated mortality on HIV treatment among active patients and patients lost to
follow-up in 4 provinces of Zambia: Findings from a multistage sampling-based
survey.
AB - BACKGROUND: Survival represents the single most important indicator of successful
HIV treatment. Routine monitoring fails to capture most deaths. As a result, both
regional assessments of the impact of HIV services and identification of hotspots
for improvement efforts are limited. We sought to assess true mortality on
treatment, characterize the extent under-reporting of mortality in routine health
information systems in Zambia, and identify drivers of mortality across sites and
over time using a multistage, regionally representative sampling approach.
METHODS AND FINDINGS: We enumerated all HIV infected adults on antiretroviral
therapy (ART) who visited any one of 64 facilities across 4 provinces in Zambia
during the 24-month period from 1 August 2013 to 31 July 2015. We identified a
probability sample of patients who were lost to follow-up through selecting
facilities probability proportional to size and then a simple random sample of
lost patients. Outcomes among patients lost to follow-up were incorporated into
survival analysis and multivariate regression through probability weights. Of
165,464 individuals (64% female, median age 39 years (IQR 33-46), median CD4 201
cells/mm3 (IQR 111-312), the 2-year cumulative incidence of mortality increased
from 1.9% (95% CI 1.7%-2.0%) to a corrected rate of 7.0% (95% CI 5.7%-8.4%) (all
ART users) and from 2.1% (95% CI 1.8%-2.4%) to 8.3% (95% CI 6.1%-10.7%) (new ART
users). Revised provincial mortality rates ranged from 3-9 times higher than
naive rates for new ART users and were lowest in Lusaka Province (4.6 per 100
person-years) and highest in Western Province (8.7 per 100 person-years) after
correction. Corrected mortality rates varied markedly by clinic, with an IQR of
3.5 to 7.5 deaths per 100 person-years and a high of 13.4 deaths per 100 person
years among new ART users, even after adjustment for clinical (e.g., pretherapy
CD4) and contextual (e.g., province and clinic size) factors. Mortality rates
(all ART users) were highest year 1 after treatment at 4.6/100 person-years (95%
CI 3.9-5.5), 2.9/100 person-years (95% CI 2.1-3.9) in year 2, and approximately
1.6% per year through 8 years on treatment. In multivariate analysis, patient
level factors including male sex and pretherapy CD4 levels and WHO stage were
associated with higher mortality among new ART users, while male sex and HIV
disclosure were associated with mortality among all ART users. In both cases,
being late (>14 days late for appointment) or lost (>90 days late for an
appointment) was associated with deaths. We were unable to ascertain the vital
status of about one-quarter of those lost and selected for tracing and did not
adjudicate causes of death. CONCLUSIONS: HIV treatment in Zambia is not optimally
effective. The high and sustained mortality rates and marked under-reporting of
mortality at the provincial-level and unexplained heterogeneity between regions
and sites suggest opportunities for the use of corrected mortality rates for
quality improvement. A regionally representative sampling-based approach can
bring gaps and opportunities for programs into clear epidemiological focus for
local and global decision makers.
PMID- 29329302
TI - Phylogeography and conservation genetics of the rare and relict Bretschneidera
sinensis (Akaniaceae).
AB - Bretschneidera sinensis, a class-I protected wild plant in China, is a relic of
the ancient Tertiary tropical flora endemic to Asia. However, little is known
about its genetics and phylogeography. To elucidate the current phylogeographic
patterns and infer the historical population dynamics of B. sinensis, and to make
recommendations for its conservation, three non-coding regions of chloroplast DNA
(trnQ-rps16, rps8-rps11, and trnT-trnL) were amplified and sequenced across 256
individuals from 23 populations of B. sinensis, spanning 10 provinces of China.
We recognized 13 haplotypes, demonstrating relatively high total haplotype
diversity (hT = 0.739). Almost all of the variation existed among populations
(98.09%, P < 0.001), but that within populations was low (1.91%, P < 0.001).
Strong genetic differentiation was detected among populations (GST = 0.855, P <
0.001) with limited estimations of seed flow (Nm = 0.09), indicating that
populations were strongly isolated from one another. According to SAMOVA
analysis, populations of B. sinensis in China could be divided into five
geographic groups: (1) eastern Yunnan to western Guangxi; (2) Guizhou-Hunan
Hubei; (3) central Guangdong; (4) northwestern Guangdong; and (5) the Luoxiao
Nanling-Wuyi -Yangming Mountain. Network analysis showed that the most ancestral
haplotypes were located in the first group, i.e., the eastern Yungui Plateau and
in eastern Yunnan, which is regarded as a putative glacial refugia for B.
sinensis in China. B. sinensis may have expanded its range eastward from these
refugia and experienced bottleneck or founder effects in southeastern China.
Populations in Liping (Guizhou Province), Longsheng (Guangxi Province), Huizhou
(Guangdong Province), Chongyi (Jiangxi Province), Dong-an (Hunan Province),
Pingbian (Yunnan Province) and Xinning (Hunan Province) are proposed as the
priority protection units.
PMID- 29329303
TI - Efficacy of lateral- versus medial-approach hip joint capsule denervation as
surgical treatments of the hip joint pain; a neuronal tract tracing study in the
sheep.
AB - OBJECTIVE: To evaluate efficacy of denervation of the of the hip joint capsule
(HJC), as a treatment of hip joint pain. Specifically, we tested the hypothesis
that HJC denervation will significantly reduce the number of sensory neurons
innervating the capsule. STUDY DESIGN: Denervation of the HJC from a medial or
lateral approach was followed by retrograde tracing of sensory neurons
innervating the capsule. ANIMALS: Twenty adult male sheep (30-40 kg of body
weight; Polish merino breed) were used in the study. METHODS: The hip joint was
denervated from medial (n = 5) or lateral (n = 5) surgical approaches.
Immediately after denervation, the retrograde neural tract tracer Fast Blue (FB)
was injected into the HJC. An additional ten animals (n = 5 for medial and n = 5
for lateral approach) received the same treatment without HJC denervation to
provide the appropriate controls. RESULTS: Results of the study revealed that the
vast majority of retrogradely labelled sensory neurons innervating the HJC
originate from fifth lumbar to second sacral dorsal root ganglia. Both the medial
and the lateral denervations significantly reduced the number of sensory neurons
innervating the HJC (39.2% and 69.0% reduction respectively). CONCLUSIONS: These
results show that denervation of the HJC is an effective surgical procedure for
reduction of the sensory neuronal input to the HJC. Moreover, the lateral
approach was found to be significantly more effective for reducing sensory
innervation as compared to the medial one.
PMID- 29329304
TI - A novel method to test associations between a weighted combination of phenotypes
and genetic variants.
AB - Many complex diseases like diabetes, hypertension, metabolic syndrome, et cetera,
are measured by multiple correlated phenotypes. However, most genome-wide
association studies (GWAS) focus on one phenotype of interest or study multiple
phenotypes separately for identifying genetic variants associated with complex
diseases. Analyzing one phenotype or the related phenotypes separately may lose
power due to ignoring the information obtained by combining phenotypes, such as
the correlation between phenotypes. In order to increase statistical power to
detect genetic variants associated with complex diseases, we develop a novel
method to test a weighted combination of multiple phenotypes (WCmulP). We perform
extensive simulation studies as well as real data (COPDGene) analysis to evaluate
the performance of the proposed method. Our simulation results show that WCmulP
has correct type I error rates and is either the most powerful test or comparable
to the most powerful test among the methods we compared. WCmulP also has an
outstanding performance for identifying single-nucleotide polymorphisms (SNPs)
associated with COPD-related phenotypes.
PMID- 29329305
TI - Evaluating the efficacy of switching from lamivudine plus adefovir to tenofovir
disoproxil fumarate monotherapy in lamivudine-resistant stable hepatitis B
patients.
AB - BACKGROUND: The efficacy of switching to tenofovir disoproxil fumarate (TDF)
monotherapy from lamivudine (LAM) plus adefovir dipivoxil (ADV) combination
therapy (stable switching) in patients with LAM-resistant chronic hepatitis B
(CHB) and undetectable hepatitis B virus (HBV) DNA is not clear. METHODS: In this
non-inferiority trial, patients with LAM-resistant CHB and undetectable serum HBV
DNA (<20 IU/mL) for >6 months after initiating LAM+ADV combination therapy were
randomized (1:2) either to continue the combination therapy (LAM+ADV group, n =
58) or switched to TDF monotherapy (TDF group, n = 111). They were followed-up
with serum biochemistry tests and HBV DNA measurement at 12-week intervals for 96
weeks. The primary endpoint of this study was the proportion of patients with
viral reactivation at week 96. RESULTS: Patients with CHB enrolled in this study
(n = 169) included 74 patients with compensated liver cirrhosis. In total, 9
patients (4 in the LAM+ADV group and 5 in the TDF group) dropped-out from the
study. After a mean follow-up period of 96 weeks, the proportion of HBV
reactivation observed was 6.8% (4/58) in the LAM+ADV group and 4.5% (5/111) in
the TDF group by using intention-to-treat analysis (difference, -2.3%; 95% CI,
9.84-5.24%). None of the subjects in either group experienced viral reactivation
based on per protocol analysis. No serious adverse reactions were observed. In
the subgroup analysis for estimated glomerular filtration rate (eGFR) before and
after treatment, decreased eGFR was observed only in the TDF group with cirrhosis
(85.22 vs. 79.83 mL/min/1.73 m2, p = 0.000). CONCLUSIONS: Stable switching to TDF
monotherapy yielded non-inferior results at 96 weeks compared to the results
obtained with LAM+ADV combination therapy in patients with LAM-resistant CHB and
undetectable HBV DNA. However, TDF monotherapy in patients with cirrhosis
requires close attention with respect to renal function. TRIAL REGISTRATION:
ClinicalTrials.gov NCT01732367.
PMID- 29329306
TI - Lifespan extension without fertility reduction following dietary addition of the
autophagy activator Torin1 in Drosophila melanogaster.
AB - Autophagy is a highly conserved mechanism for cellular repair that becomes
progressively down-regulated during normal ageing. Hence, manipulations that
activate autophagy could increase lifespan. Previous reports show that
manipulations to the autophagy pathway can result in longevity extension in
yeast, flies, worms and mammals. Under standard nutrition, autophagy is inhibited
by the nutrient sensing kinase Target of Rapamycin (TOR). Therefore,
manipulations of TOR that increase autophagy may offer a mechanism for extending
lifespan. Ideally, such manipulations should be specific and minimise off-target
effects, and it is important to discover additional methods for 'clean' lifespan
manipulation. Here we report an initial study into the effect of up-regulating
autophagy on lifespan and fertility in Drosophila melanogaster by dietary
addition of Torin1. Activation of autophagy using this selective TOR inhibitor
was associated with significantly increased lifespan in both sexes. Torin1
induced a dose-dependent increase in lifespan in once-mated females. There was no
evidence of a trade-off between longevity and fecundity or fertility. Torin1-fed
females exhibited significantly elevated fecundity, but also elevated egg
infertility, resulting in no net change in overall fertility. This supports the
idea that lifespan can be extended without trade-offs in fertility and suggest
that Torin1 may be a useful tool with which to pursue anti-ageing research.
PMID- 29329307
TI - Response time scores on a reflexive attention task predict a child's inattention
score from a parent report.
AB - Compared to sustained attention, only a small proportion of studies examine
reflexive attention as a component of everyday attention. Understanding the
significance of reflexive attention to everyday attention may inform better
treatments for attentional disorders. Children from a general population
(recruited when they were from 9-16 years old) completed an exogenously-cued task
measuring the extent to which attention is captured by peripheral cue-target
conditions. Parents completed a questionnaire reporting their child's day-to-day
attention. A general linear model indicated that parent-rated inattention
predicted the increase in response time over baseline when a bright cue preceded
the target (whether it was valid or invalid) but not when a dim cue preceded the
target. More attentive children had more pronounced response time increases from
baseline. Our findings suggest a link between a basic measure of cognition
(response time difference scores) and parent observations. The findings have
implications for increased understanding of the role of reflexive attention in
the everyday attention of children.
PMID- 29329309
TI - Time series sightability modeling of animal populations.
AB - Logistic regression models-or "sightability models"-fit to detection/non
detection data from marked individuals are often used to adjust for visibility
bias in later detection-only surveys, with population abundance estimated using a
modified Horvitz-Thompson (mHT) estimator. More recently, a model-based
alternative for analyzing combined detection/non-detection and detection-only
data was developed. This approach seemed promising, since it resulted in similar
estimates as the mHT when applied to data from moose (Alces alces) surveys in
Minnesota. More importantly, it provided a framework for developing flexible
models for analyzing multiyear detection-only survey data in combination with
detection/non-detection data. During initial attempts to extend the model-based
approach to multiple years of detection-only data, we found that estimates of
detection probabilities and population abundance were sensitive to the amount of
detection-only data included in the combined (detection/non-detection and
detection-only) analysis. Subsequently, we developed a robust hierarchical
modeling approach where sightability model parameters are informed only by the
detection/non-detection data, and we used this approach to fit a fixed-effects
model (FE model) with year-specific parameters and a temporally-smoothed model
(TS model) that shares information across years via random effects and a temporal
spline. The abundance estimates from the TS model were more precise, with
decreased interannual variability relative to the FE model and mHT abundance
estimates, illustrating the potential benefits from model-based approaches that
allow information to be shared across years.
PMID- 29329308
TI - Modeling the effect of boost timing in murine irradiated sporozoite prime-boost
vaccines.
AB - Vaccination with radiation-attenuated sporozoites has been shown to induce CD8+ T
cell-mediated protection against pre-erythrocytic stages of malaria. Empirical
evidence suggests that successive inoculations often improve the efficacy of this
type of vaccines. An initial dose (prime) triggers a specific cellular response,
and subsequent inoculations (boost) amplify this response to create a robust CD8+
T cell memory. In this work we propose a model to analyze the effect of T cell
dynamics on the performance of prime-boost vaccines. This model suggests that
boost doses and timings should be selected according to the T cell response
elicited by priming. Specifically, boosting during late stages of clonal
contraction would maximize T cell memory production for vaccines using lower
doses of irradiated sporozoites. In contrast, single-dose inoculations would be
indicated for higher vaccine doses. Experimental data have been obtained that
support theoretical predictions of the model.
PMID- 29329310
TI - Medication discrepancies across multiple care transitions: A retrospective
longitudinal cohort study in Italy.
AB - PURPOSE: Medication discrepancies are defined as unexplained differences among
regimens across different sites of care. The problem of medication discrepancies
that occur during the entire care pathway from hospital admission to a local care
setting discharge (namely all types of settings dedicated to formal care other
than hospitals) has received little attention in the medical literature. The
present study aims to (1) determine the prevalence of medication discrepancies
that occur during the entire care pathway from hospital admission to local care
setting discharge, (2) describe the discrepancy and medication type, and (3)
identify potential risk factors for experiencing medication discrepancies in
patient care transitions. Evidence from an integrated health care system, such as
the Italian one, may explain results from other studies in different healthcare
systems. METHODS: A retrospective longitudinal cohort study of patients admitted
from July 2015 to July 2016 to the Giovanni Bosco Hospital serving Turin, Italy
and its surrounding territory was performed. Discrepancies were recorded at the
following four care transitions: T1: Hospital admission; T2: Hospital discharge;
T3: Admission into local care settings; T4: Discharge from local care settings.
All evaluations were based on documented regimens and were performed by a team
(doctor, nurse and pharmacists). RESULTS: Of 366 included patients, 25.68% had at
least one discrepancy. The most frequent type of discrepancy was from medication
omission (N = 74; 71.15%). Only discharge from a long-stay care setting (T4) was
significantly associated with the onset of discrepancies (p = 0.045). When
considering a lack of adequate documentation, not as missing data but as a
discrepancy, 43.72% of patients had at least one discrepancy. CONCLUSIONS: This
study suggests that an integrated health care system, such as Italian system, may
influence the prevalence of discrepancies, thus highlighting the need for
structured multidisciplinary and, if possible, computerized medication
reconciliation to prevent medication discrepancies and improve the quality of
medical documentation.
PMID- 29329311
TI - Harmonized clinical trial methodologies for localized cutaneous leishmaniasis and
potential for extensive network with capacities for clinical evaluation.
AB - INTRODUCTION: Progress with the treatment of cutaneous leishmaniasis (CL) has
been hampered by inconsistent methodologies used to assess treatment effects. A
sizable number of trials conducted over the years has generated only weak
evidence backing current treatment recommendations, as shown by systematic
reviews on old-world and new-world CL (OWCL and NWCL). MATERIALS AND METHODS:
Using a previously published guidance paper on CL treatment trial methodology as
the reference, consensus was sought on key parameters including core eligibility
and outcome measures, among OWCL (7 countries, 10 trial sites) and NWCL (7
countries, 11 trial sites) during two separate meetings. RESULTS: Findings and
level of consensus within and between OWCL and NWCL sites are presented and
discussed. In addition, CL trial site characteristics and capacities are
summarized. CONCLUSIONS: The consensus reached allows standardization of future
clinical research across OWCL and NWCL sites. We encourage CL researchers to
adopt and adapt as required the proposed parameters and outcomes in their future
trials and provide feedback on their experience. The expertise afforded between
the two sets of clinical sites provides the basis for a powerful consortium with
potential for extensive, standardized assessment of interventions for CL and
faster approval of candidate treatments.
PMID- 29329312
TI - A computational study of the impact of inhomogeneous internodal lengths on
conduction velocity in myelinated neurons.
AB - Age-related decreases in the conduction velocity (CV) of action potentials along
myelinated axons have been linked to morphological changes in the myelin sheath.
In particular, evidence suggests the presence of segmental demyelination and
remyelination of axons. In remyelinated segments, the distance between adjacent
nodes of Ranvier is typically shorter, and myelin sheaths are thinner. Both
experimental and computational evidence indicates that shortened internodes slows
CV. In this computational study, we determine the impact of progressive segmental
demyelination and remyelination, modeled by shorter internodes with thinner
myelin sheaths interspersed with normal ones, upon the CV. We find that CV
progressively decreases as the number of remyelinated segments increases, but
this decrease is greater than one would expect from an estimate of the CV based
merely upon the number of short and long internodes. We trace the additional
suppression of the CV to transitions between long and short internodes. Our study
presents an important consideration for the precise modeling of neural circuits
with remyelinated neurons.
PMID- 29329313
TI - Development of a field testing protocol for identifying Deepwater Horizon oil
spill residues trapped near Gulf of Mexico beaches.
AB - The Deepwater Horizon (DWH) accident, one of the largest oil spills in U.S.
history, contaminated several beaches located along the Gulf of Mexico (GOM)
shoreline. The residues from the spill still continue to be deposited on some of
these beaches. Methods to track and monitor the fate of these residues require
approaches that can differentiate the DWH residues from other types of petroleum
residues. This is because, historically, the crude oil released from sources such
as natural seeps and anthropogenic discharges have also deposited other types of
petroleum residues on GOM beaches. Therefore, identifying the origin of these
residues is critical for developing effective management strategies for
monitoring the long-term environmental impacts of the DWH oil spill. Advanced
fingerprinting methods that are currently used for identifying the source of oil
spill residues require detailed laboratory studies, which can be cost
prohibitive. Also, most agencies typically use untrained workers or volunteers to
conduct shoreline monitoring surveys and these worker will not have access to
advanced laboratory facilities. Furthermore, it is impractical to routinely
fingerprint large volumes of samples that are collected after a major oil spill
event, such as the DWH spill. In this study, we propose a simple field testing
protocol that can identify DWH oil spill residues based on their unique physical
characteristics. The robustness of the method is demonstrated by testing a
variety of oil spill samples, and the results are verified by characterizing the
samples using advanced chemical fingerprinting methods. The verification data
show that the method yields results that are consistent with the results derived
from advanced fingerprinting methods. The proposed protocol is a reliable, cost
effective, practical field approach for differentiating DWH residues from other
types of petroleum residues.
PMID- 29329314
TI - Influence of monsoonal winds on chlorophyll-alpha distribution in the Beibu Gulf.
AB - The influence of seasonal, monsoonal winds on the temporal and spatial
variability of chlorophyll-a (chl-a) in the Beibu Gulf is studied based on long
term satellite data of sea surface winds, chl-a concentration and sea surface
temperature (SST) and in-situ observations for the years from 2002 to 2014. The
analysis results indicated that under northeasterly monsoonal winds, chl-a
concentrations were substantially elevated in most area of the Beibu Gulf, with a
high chl-a concentration (>2 mg m-3) patch extending southwestward from the
coastal water of the northeastern Gulf, consistent with the winter wind pattern.
Meanwhile, the spatial distribution of high chl-a concentration is correlated
with low SST in the northeastern Gulf. In the southern Gulf, there was generally
low chl-a, except in the coastal waters southwest of Hainan Island. Here, the
upwelling cold water prevails outside the mouth of the Beibu Gulf, driven by the
southwesterly monsoonal winds and the runoff from the Changhua River, as implied
by low observed SST. Correlation analysis indicated the chl-a concentration was
strongly modulated by wind speed (r = 0.63, p<0.001), particularly in the middle
of the northern Gulf and southern Hainan Island (r>0.7, p<0.001). Integrated
analysis also showed that stratification is weak and mixing is strong in winter
as affected by the high wind speed, which suggests that the wind-induced mixing
is a dominant mechanism for entrainment of nutrients and the spatial distribution
of chl-a in winter.
PMID- 29329315
TI - Role of N-glycosylation in activation of proMMP-9. A molecular dynamics
simulations study.
AB - Human matrix metalloproteinase proMMP-9 is secreted as latent zymogen, which
requires two-steps proteolytic activation. The secreted proMMP-9 is glycosylated
at two positions: Asn38 and Asn120 located in the prodomain and catalytic domain,
respectively. It has been demonstrated that glycosylation at Asn120 is required
for secretion of the enzyme, while the role of Asn38 glycosylation is not well
understood, but is usually linked to the activation process. One hypothesis
stated that the Asn38 glycosylation might protect against proteolytic activation.
However, the activation process occurs with or without the presence of this
glycosylation. We conducted molecular dynamics (MD) simulations on the
glycosylated and non-glycosylated proMMP-9 to elucidate the effect of Asn38
glycosylation on this two-step activation process. The simulation results suggest
that Asn38 glycosylation does not hinder the activation process directly, but
induces conformational changes in the vicinity of the first proteolytic region in
such a way that E59-M60 cleavage is processed before R106-F107. These results
correlate with analysis provided by Boon et al. and experimental data from Ogata
et al. who attempted to determine the order of events in activation of proMMP-9.
Results from additional MD simulations for the model of glycosylated proMMP-9
bound to galectin-8 N-domain suggest that Gal-8 by interacting with Asn38 glycan
might further facilitate processing of the first cleavage between E59-M60. Thus,
our simulation results suggest that both Asn38 glycosylation and interaction with
Gal-8N may be involved in facilitating and the temporal order of the activation
process of pro-MMP9. The aim of this report is to provide an inspiration for
future detailed experiments aimed at explaining the role of N-glycosylation in
the activation process of prodomain of MMP-9.
PMID- 29329316
TI - Electroencephalography power and coherence changes with age and motor skill
development across the first half year of life.
AB - Existing research in infants has correlated electroencephalography (EEG) measures
of power and coherence to cognitive development and to locomotor experience, but
only in infants older than 5 months of age. Our goal was to explore the
relationship between EEG measures of power and coherence and motor skill
development in younger infants who are developing reaching skill. Twenty-one
infants with typical development between 38 and 203 days of age participated.
Longitudinal EEG recording sessions were recorded in monthly increments, with 3-5
sessions acquired for 19 participants and 1 session for 2 participants, resulting
in 71 sessions in total. EEG variables of interest were relative power in the 6-9
Hz range and coherence between selected electrode pairs. We describe the
development of the peak in relative power in the 6-9 Hz frequency band of EEG; it
is not present around 1 month of age and starts to appear across the following
months. Coherence generally increased in the bilateral frontal-parietal networks,
while the interhemispheric connectivity in motor cortices generally decreased.
The results of this relatively small pilot study provide a foundational
description of neural function changes observed as motor skills are changing
across the first half year of life. This is a first step in understanding
experience-dependent plasticity of the infant brain and has the potential to aid
in the early detection of atypical brain development.
PMID- 29329317
TI - Oxidative stress caused by activation of NADPH oxidase 4 promotes contrast
induced acute kidney injury.
AB - Contrast-induced acute kidney injury (CIAKI) is a leading cause of acute kidney
injury following radiographic procedures. Intrarenal oxidative stress plays a
critical role in CIAKI. Nicotinamide adenine dinucleotide 3-phosphate (NADPH)
oxidases (Noxs) are important sources of reactive oxygen species (ROS). Among the
various types of Noxs, Nox4 is expressed predominantly in the kidney in rodents.
Here, we evaluated the role of Nox4 and benefit of Nox4 inhibition on CIAKI using
in vivo and in vitro models. HK-2 cells were treated with iohexol, with or
without Nox4 knockdown, or the most specific Nox1/4 inhibitor (GKT137831).
Effects of Nox4 inhibition on CIAKI mice were examined. Expression of Nox4 in HK
2 cells was significantly increased following iohexol exposure. Silencing of Nox4
rescued the production of ROS, downregulated pro-inflammatory markers
(particularly phospho-p38) implicated in CIAKI, and reduced Bax and caspase 3/7
activity, which resulted in increased cellular survival in iohexol-treated HK-2
cells. Pretreatment with GKT137831 replicated these effects by decreasing levels
of phospho-p38. In a CIAKI mouse model, even though the improvement of plasma
blood urea nitrogen was unclear, pretreatment with GKT137831 resulted in
preserved structure, reduced expression of 8-hydroxy-2'-deoxyguanosine (8OHdG)
and kidney injury molecule-1 (KIM-1), and reduced number of TUNEL (terminal
deoxynucleotidyl transferase dUTP nick end labeling)-positive cells. These
results suggest Nox4 as a key source of reactive oxygen species responsible for
CIAKI and provide a novel potential option for prevention of CIAKI.
PMID- 29329318
TI - Erythrocyte Inosine triphosphatase activity: A potential biomarker for adverse
events during combination antiretroviral therapy for HIV.
AB - The purine analogues tenofovir and abacavir are precursors of potential
substrates for the enzyme Inosine 5'-triphosphate pyrophosphohydrolase (ITPase).
Here, we investigated the association of ITPase activity and ITPA genotype with
the occurrence of adverse events (AEs) during combination antiretroviral therapy
(cART) for human immunodeficiency virus (HIV) infection. In 393 adult HIV
seropositive patients, AEs were defined as events that led to stop of cART
regimen. ITPase activity >=4 mmol IMP/mmol Hb/hour was considered as normal. ITPA
genotype was determined by testing two ITPA polymorphisms: c.94C>A (p.Pro32Thr,
rs1127354) and c.124+21A>C (rs7270101). Logistic regression analysis determined
odds ratios for developing AEs. In tenofovir-containing regimens decreased ITPase
activity was associated with less AEs (p = 0.01) and longer regimen duration (p =
0.001). In contrast, in abacavir-containing regimens decreased ITPase activity
was associated with more AEs (crude p = 0.02) and increased switching of
medication due to AEs (p = 0.03). ITPA genotype wt/wt was significantly
associated with an increase in the occurrence of AEs in tenofovir-containing
regimens. Decreased ITPase activity seems to be protective against occurrence of
AEs in tenofovir-containing cART, while it is associated with an increase in AEs
in abacavir-containing regimens.
PMID- 29329319
TI - Comparative analysis of uranium bioassociation with halophilic bacteria and
archaea.
AB - Rock salt represents a potential host rock formation for the final disposal of
radioactive waste. The interactions between indigenous microorganisms and
radionuclides, e.g. uranium, need to be investigated to better predict the
influence of microorganisms on the safety assessment of the repository. Hence,
the association process of uranium with two microorganisms isolated from rock
salt was comparatively studied. Brachybacterium sp. G1, which was isolated from
the German salt dome Gorleben, and Halobacterium noricense DSM15987T, were
selected as examples of a moderately halophilic bacterium and an extremely
halophilic archaeon, respectively. The microorganisms exhibited completely
different association behaviors with uranium. While a pure biosorption process
took place with Brachybacterium sp. G1 cells, a multistage association process
occurred with the archaeon. In addition to batch experiments, in situ attenuated
total reflection Fourier-transform infrared spectroscopy was applied to
characterize the U(VI) interaction process. Biosorption was identified as the
dominating process for Brachybacterium sp. G1 with this method. Carboxylic
functionalities are the dominant interacting groups for the bacterium, whereas
phosphoryl groups are also involved in U(VI) association by the archaeon H.
noricense.
PMID- 29329320
TI - Atypical E2f functions are critical for pancreas polyploidization.
AB - The presence of polyploid cells in the endocrine and exocrine pancreas has been
reported for four decades. In rodents, pancreatic polyploidization is initiated
after weaning and the number of polyploid cells increases with age. Surprisingly
the molecular regulators and biological functions of polyploidization in the
pancreas are still unknown. We discovered that atypical E2f activity is essential
for polyploidization in the pancreas, using an inducible Cre/LoxP approach in new
born mice to delete ubiquitously the atypical E2f transcription factors, E2f7 and
E2f8. In contrast to its critical role in embryonic survival, conditional
deletion of both of both atypical E2fs in newborn mice had no impact on postnatal
survival and mice lived until old age. However, deficiency of E2f7 or E2f8 alone
was sufficient to suppress polyploidization in the pancreas and associated with
only a minor decrease in blood serum levels of glucose, insulin, amylase and
lipase under 4 hours starvation condition compared to wildtype littermates. In
mice with fewer pancreatic polyploid cells that were fed ad libitum, no major
impact on hormones or enzymes levels was observed. In summary, we identified
atypical E2fs to be essential for polyploidization in the pancreas and discovered
that postnatal induced loss of both atypical E2fs in many organs is compatible
with life until old age.
PMID- 29329321
TI - Impact of lipopolysaccharide-induced acute inflammation on baroreflex-controlled
sympathetic arterial pressure regulation.
AB - BACKGROUND: Lipopolysaccharide (LPS) induces acute inflammation, activates
sympathetic nerve activity (SNA) and alters hemodynamics. Since the arterial
baroreflex is a negative feedback system to stabilize arterial pressure (AP),
examining the arterial baroreflex function is a prerequisite to understanding
complex hemodynamics under LPS challenge. We investigated the impact of LPS
induced acute inflammation on SNA and AP regulation by performing baroreflex open
loop analysis. METHODS: Ten anesthetized Sprague-Dawley rats were used. Acute
inflammation was induced by an intravenous injection of LPS (60 MUg/kg). We
isolated the carotid sinuses from the systemic circulation and controlled carotid
sinus pressure (CSP) by a servo-controlled piston pump. We matched CSP to AP to
establish the baroreflex closed-loop condition, whereas we decoupled CSP from AP
to establish the baroreflex open-loop condition and changed CSP stepwise to
evaluate the baroreflex open-loop function. We recorded splanchnic SNA and
hemodynamic parameters under baroreflex open- and closed-loop conditions at
baseline and at 60 and 120 min after LPS injection. RESULTS: In the baroreflex
closed-loop condition, SNA continued to increase after LPS injection, reaching
three-fold the baseline value at 120 min (baseline: 94.7 +/- 3.6 vs. 120 min:
283.9 +/- 31.9 a.u.). In contrast, AP increased initially (until 75 min), then
declined to the baseline level. In the baroreflex open-loop condition, LPS reset
the neural arc (CSP-SNA relationship) upward to higher SNA, while shifted the
peripheral arc (SNA-AP relationship) downward at 120 min after the injection. As
a result, the operating point determined by the intersection between function
curves of neural arc and peripheral arc showed marked sympatho-excitation without
substantial changes in AP. CONCLUSIONS: LPS-induced acute inflammation markedly
increased SNA via resetting of the baroreflex neural arc, and suppressed the
peripheral arc. The balance between the augmented neural arc and suppressed
peripheral arc determines SNA and hemodynamics in LPS-induced acute inflammation.
PMID- 29329322
TI - Methylene-tetrahydrofolate reductase contributes to allergic airway disease.
AB - RATIONALE: Environmental exposures strongly influence the development and
progression of asthma. We have previously demonstrated that mice exposed to a
diet enriched with methyl donors during vulnerable periods of fetal development
can enhance the heritable risk of allergic airway disease through epigenetic
changes. There is conflicting evidence on the role of folate (one of the primary
methyl donors) in modifying allergic airway disease. OBJECTIVES: We hypothesized
that blocking folate metabolism through the loss of methylene-tetrahydrofolate
reductase (Mthfr) activity would reduce the allergic airway disease phenotype
through epigenetic mechanisms. METHODS: Allergic airway disease was induced in
C57BL/6 and C57BL/6Mthfr-/- mice through house dust mite (HDM) exposure. Airway
inflammation and airway hyperresponsiveness (AHR) were measured between the two
groups. Gene expression and methylation profiles were generated for whole lung
tissue. Disease and molecular outcomes were evaluated in C57BL/6 and C57BL/6Mthfr
/- mice supplemented with betaine. MEASUREMENTS AND MAIN RESULTS: Loss of Mthfr
alters single carbon metabolite levels in the lung and serum including elevated
homocysteine and cystathionine and reduced methionine. HDM-treated C57BL/6Mthfr-/
mice demonstrated significantly less airway hyperreactivity (AHR) compared to
HDM-treated C57BL/6 mice. Furthermore, HDM-treated C57BL/6Mthfr-/- mice compared
to HDM-treated C57BL/6 mice have reduced whole lung lavage (WLL) cellularity,
eosinophilia, and Il-4/Il-5 cytokine concentrations. Betaine supplementation
reversed parts of the HDM-induced allergic airway disease that are modified by
Mthfr loss. 737 genes are differentially expressed and 146 regions are
differentially methylated in lung tissue from HDM-treated C57BL/6Mthfr-/- mice
and HDM-treated C57BL/6 mice. Additionally, analysis of methylation/expression
relationships identified 503 significant correlations. CONCLUSION: Collectively,
these findings indicate that the loss of folate as a methyl donor is a modifier
of allergic airway disease, and that epigenetic and expression changes correlate
with this modification. Further investigation into the mechanisms that drive this
observation is warranted.
PMID- 29329323
TI - Stroke risk and outcomes in patients with chronic kidney disease or end-stage
renal disease: Two nationwide studies.
AB - BACKGROUND AND AIMS: Because the risk and outcomes of stroke in patients with
chronic kidney disease (CKD) or end-stage renal disease (ESRD) were unclear, we
evaluated these risks using a retrospective cohort study and a nested cohort
study. METHODS: We used Taiwan's National Health Insurance Research Database to
identify 1378 patients aged >=20 years who had ESRD in 2000-2004. An age- and sex
matched CKD cohort (n = 5512) and a control cohort (n = 11,024) were selected for
comparison. Events of incident stroke were considered as outcome during the
follow-up period in 2000-2013, and we calculated adjusted hazard ratios (HR) and
95% CIs of stroke associated with CKD or ESRD. We further used matching procedure
with propensity score to estimate the risk of stroke for control group, CKD
patients, and EDRD patients. A nested cohort study of 318,638 hospitalized stroke
patients between 2000 and 2010 also was conducted to analyze the impact of CKD
and ESRD on post-stroke mortality. RESULTS: Before propensity-score matching, the
incidences of stroke for controls, CKD patients and ESRD patients were 6.57,
13.3, and 21.7 per 1000 person-years, respectively. Compared with control group,
the adjusted HRs of stroke were 1.49 (95% CI, 1.32-1.68) and 2.39 (95% CI, 1.39
2.87) for people with CKD or ESRD respectively, and were significantly higher in
both sexes and every age group. After propensity-score matching, the HRs of
stroke for patients with CKD and ESRD were 1.51 (95% CI 1.24-1.85) and 2.08 (95%
CI 1.32-3.26), respectively, during the follow-up period. Among hospitalized
stroke patients, adjusted rate ratio (RR) of post-stroke mortality in CKD and
ESRD cohorts were 1.44 (95% CI, 1.33-1.56) and 2.62 (95% CI, 2.43-2.82)
respectively compared with control. CONCLUSIONS: CKD and ESRD patient groups thus
faced significantly higher risk of stroke and post-stroke mortality. Risk factor
identification and preventive strategies are needed to minimize stroke risk and
post-stroke mortality in these vulnerable patient groups.
PMID- 29329325
TI - Classification of patients with knee osteoarthritis in clinical phenotypes: Data
from the osteoarthritis initiative.
AB - OBJECTIVES: The existence of phenotypes has been hypothesized to explain the
large heterogeneity characterizing the knee osteoarthritis. In a previous
systematic review of the literature, six main phenotypes were identified: Minimal
Joint Disease (MJD), Malaligned Biomechanical (MB), Chronic Pain (CP),
Inflammatory (I), Metabolic Syndrome (MS) and Bone and Cartilage Metabolism
(BCM). The purpose of this study was to classify a sample of individuals with
knee osteoarthritis (KOA) into pre-defined groups characterized by specific
variables that can be linked to different disease mechanisms, and compare these
phenotypes for demographic and health outcomes. METHODS: 599 patients were
selected from the OAI database FNIH at 24 months' time to conduct the study. For
each phenotype, cut offs of key variables were identified matching the results
from previous studies in the field and the data available for the sample. The
selection process consisted of 3 steps. At the end of each step, the subjects
classified were excluded from the further classification stages. Patients meeting
the criteria for more than one phenotype were classified separately into a
'complex KOA' group. RESULTS: Phenotype allocation (including complex KOA) was
successful for 84% of cases with an overlap of 20%. Disease duration was shorter
in the MJD while the CP phenotype included a larger number of Women (81%). A
significant effect of phenotypes on WOMAC pain (F = 16.736 p <0.001) and WOMAC
physical function (F = 14.676, p < 0.001) was identified after controlling for
disease duration. CONCLUSION: This study signifies the feasibility of a
classification of KOA subjects in distinct phenotypes based on subgroup-specific
characteristics.
PMID- 29329324
TI - Variability and cost implications of three generations of the Roche
LightCycler(r) 480.
AB - Real time PCR has become a dominant method for the highly sensitive detection of
pathogens in clinical material. Real time PCR can generate a fluorescence signal
by using fluorescence labelled probes, allowing us to detect and semi quantify
the amount of amplified DNA. Here we test the variability of the detection system
and cost implications of three different versions of the LightCycler(r) 480
(LC480), focusing on the intensity of fluorescence and Cq in monoplex and
multiplex rtPCRs. For gastro-intestinal pathogens there was no correlation
between the intensity of fluorescence and the Cq value in the different LC480
types. For probes with the dyes FAMTM, HEXTM, Cy5 and Red610 a higher
fluorescence intensity was seen in LC480 type II and III compared to LC480 type
I. After lowering the probe concentration for the Cy5 dye three-fold (from 0.3MUM
to 0.1MUM) the Cq value remains the same and the intensity of fluorescence
decreases. For the LC480 type II and III the difference in fluorescence intensity
was much more extreme. The concentration of the different labelled probes can be
lowered at least six-fold in LC480 type II and III cyclers while maintaining a
fluorescence intensity as high as achieved in the LC480 type I with undiluted
probe. In conclusion, the strength of the fluorescence signal of the
LightCycler(r) 480 type III is superior to that of LightCycler(r) 480 types I and
II, allowing the use of lower probe concentrations for all dyes, particularly for
the dyes Red610 and Cy5. This results in a two thirds reduction in PCR probe
costs. Switching to these newer machines for real-time PCR can reduce dye
labelled probe consumption and thus reduce costs significantly.
PMID- 29329326
TI - Utilization of peptide phage display to investigate hotspots on IL-17A and what
it means for drug discovery.
AB - To date, IL-17A antibodies remain the only therapeutic approach to correct the
abnormal activation of the IL-17A/IL-17R signaling complex. Why is it that
despite the remarkable success of IL-17 antibodies, there is no small molecule
antagonist of IL-17A in the clinic? Here we offer a unique approach to address
this question. In order to understand the interaction of IL-17A with its
receptor, we combined peptide discovery using phage display with HDX,
crystallography, and functional assays to map and characterize hot regions that
contribute to most of the energetics of the IL-17A/IL-17R interaction. These
functional maps are proposed to serve as a guide to aid in the development of
small molecules that bind to IL-17A and block its interaction with IL-17RA.
PMID- 29329327
TI - Selection of housekeeping genes and demonstration of RNAi in cotton leafhopper,
Amrasca biguttula biguttula (Ishida).
AB - Amrasca biguttula biguttula (Ishida) commonly known as cotton leafhopper is a
severe pest of cotton and okra. Not much is known on this insect at molecular
level due to lack of genomic and transcriptomic data. To prepare for functional
genomic studies in this insect, we evaluated 15 common housekeeping genes (Tub, B
Tub, EF alpha, GADPH, UbiCF, RP13, Ubiq, G3PD, VATPase, Actin, 18s, 28s, TATA,
ETF, SOD and Cytolytic actin) during different developmental stages and under
starvation stress. We selected early (1st and 2nd), late (3rd and 4th) stage
nymphs and adults for identification of stable housekeeping genes using geNorm,
NormFinder, BestKeeper and RefFinder software. Based on the different algorithms,
RP13 and VATPase are identified as the most suitable reference genes for
quantification of gene expression by reverse transcriptase quantitative PCR (RT
qPCR). Based on RefFinder which comprehended the results of three algorithms,
RP13 in adults, Tubulin (Tub) in late nymphs, 28S in early nymph and UbiCF under
starvation stress were identified as the most stable genes. We also developed
methods for feeding double-stranded RNA (dsRNA) incorporated in the diet. Feeding
dsRNA targeting Snf7, IAP, AQP1, and VATPase caused 56.17-77.12% knockdown of
targeted genes compared to control and 16 to 48% mortality of treated insects
when compared to control.
PMID- 29329328
TI - Early occurrence of inspiratory muscle weakness in Parkinson's disease.
AB - INTRODUCTION: In Parkinson's disease (PD), respiratory insufficiency (including
functional and muscle disorders) can impact dysarthria and swallowing. Most
studies of this topic have been performed retrospectively in populations of
patients with advanced PD. The objective of the present study was to characterize
lung function (under off-drug conditions) in early-stage PD patients at baseline
and then again two years later. METHODS: Forty-one early-stage PD patients (mean
+/- SD age: 61.7 +/- 7.7; mean +/- SD disease duration: 1.9 +/- 1.7 years) were
prospectively enrolled and compared with 36 age-matched healthy controls.
Neurological evaluations and pulmonary function testing were performed in the off
drug condition at the inclusion visit and then two years later. RESULTS:
Pulmonary function testing did not reveal any restrictive or obstructive
disorders; at baseline, inspiratory muscle weakness was the only abnormality
observed in the PD group (in 53.7% of the patients, vs. 25% in controls; p =
0.0105). The PD patients had a lower mean maximal inspiratory mouth pressure than
controls and a lower sniff nasal inspiratory pressure. Two years after the
initiation of chronic treatment with antiparkinsonian medications, the maximal
inspiratory mouth pressure and the sniff nasal inspiratory pressure tended to be
higher. Lastly, overall motor outcomes were not significantly worse in patients
with inspiratory muscle weakness than in patients without inspiratory muscle
weakness. CONCLUSION: Inspiratory muscle weakness seems to be common in patients
with early-stage PD, and was seen to be stable over a two-year period. Additional
long-term follow-up studies are required to specify the impact of this new
feature of PD.
PMID- 29329329
TI - Prevalence, risk factors and molecular evaluation of hepatitis E virus infection
among pregnant women resident in the northern shores of Persian Gulf, Iran.
AB - BACKGROUND: Although Iran is reported to be an endemic country for hepatitis E
virus (HEV), data on the prevalence of HEV infection among pregnant women are
scarce and the epidemiology of HEV is unknown in most parts of the country.
Therefore, this study was conducted to elucidate the prevalence, risk factors and
genotypic pattern of HEV infection among pregnant women resident in the northern
shores of Persian Gulf. This is the first report on the epidemiology of HEV
infection among pregnant women in this territory. METHODS: From October 2016 to
May 2017, 1331 pregnant women participated in this study. The mean age +/- SD of
participants was 27.93+/-5.7 years with a range of 14-45 years. Serum samples of
pregnant women were screened for the presence of anti-HEV total antibodies, anti
HEV IgG and anti-HEV IgM using commercially available ELISA kits (DIA.PRO, Milan,
Italy). All anti-HEV IgG and anti-HEV IgM positive samples were tested for HEV
RNA using two independent reverse transcriptase polymerase chain reaction (RT
PCR) assays, targeting ORF2 and ORF3 of HEV genome. In addition, 92 anti-HEV
seronegative samples as well as 50 pooled seronegative samples were evaluated by
two independent RT-PCR assays for validation of results. RESULTS: Of the 1331
pregnant women, 84 women (6.3%, 95% CI: 5.1%-7.7%) were positive for anti-HEV
antibodies, of which 83 women had anti-HEV IgG, and 11 women (0.83%, 95% CI:
0.47%-1.47%) had anti-HEV IgM. The highest rate of HEV seroprevalence was
observed among Afghan immigrants (68.0%), uneducated pregnant women (46.51%) and
those residents in Bushehr city (8.75%). All anti-HEV IgG and/or IgM positive
samples were found to be negative for HEV RNA. In addition, all of the evaluated
anti-HEV seronegative samples were negative for HEV RNA. HEV seropositivity among
pregnant women was statistically associated with age, ethnicity, place of
residence, number of pregnancies, and level of education. So that, low education
levels, Afghan, residence in Bushehr city, age group >34 years, and more parities
were risk factors for exposure to HEV. In contrast, HEV seropositivity was not
associated with stage of gestation, history of abortion, and time of sampling.
CONCLUSION: The northern shores of Persian Gulf in Iran, with HEV seroprevalence
of 6.3%, can be classified as an endemic geographical region for hepatitis E, and
residents of Bushehr city, Afghan immigrants and uneducated women are the main at
risk populations in this territory.
PMID- 29329330
TI - Obesity and abnormal glucose tolerance in offspring of diabetic mothers: A
systematic review and meta-analysis.
AB - BACKGROUND: Rising prevalence of childhood obesity and type 2 diabetes mellitus
(T2DM) is an emerging public health issue. OBJECTIVES: To investigate the
association of maternal hyperglycemia exposure during pregnancy with obesity and
abnormal glucose tolerance in offspring, and the age at occurrence. METHODS: We
searched MEDLINE and EMBASE for observational studies on obesity and diabetes in
offspring of diabetic mothers (gestational diabetes mellitus (GDM), type 1
diabetes mellitus (T1DM) and T2DM), and those on non-diabetic mothers. We
performed fixed effect meta-analysis for all studies except when heterogeneity
was detected. The quality of studies was evaluated using the Risk of Bias
Assessment Tool for Nonrandomized Studies (RoBANS). RESULTS: Twenty observational
studies were included involving a total of 26,509 children. Offspring of GDM
mother had higher BMI z-score in childhood (pooled MD: 0.14, 95%CI: 0.04-0.24,
seven studies, 21,691children, low quality of evidence). Offspring of T1DM
mothers had higher BMI z-score from prepubertal to adolescent (pooled MD: 0.35,
95% CI: 0.13-0.58, three studies, 844 children, low quality of evidence) compared
with control. After adjustment for maternal pre-pregnancy BMI, this association
remained in offspring of T1DM, but disappeared in those of GDM mothers. Offspring
of GDM mother had higher 2-hour plasma glucose from prepubertal to early
adulthood (pooled MD: 0.43 mmol/L, 95% CI: 0.18-0.69, five studies, 890
children), while those of T1DM mothers had higher rate of T2DM in 2-5 years old
to early adulthood (pooled odds ratio [OR], 6.10: 95% CI: 1.23-30.37, two
studies, 448 children, very low quality of evidence) compared with control. As
there was only one study with offspring of T2DM mothers, evidence is sparse.
LIMITATIONS: Only observational studies were included, with a few adequately
adjusted for covariables. CONCLUSIONS: Exposure to maternal hyperglycemia was
associated with offspring obesity and abnormal glucose tolerance especially in
offspring of T1DM mothers, but the evidence relies on observational studies with
low quality of evidence only.
PMID- 29329331
TI - Performance similarities predict collective benefits in dyadic and triadic joint
visual search.
AB - When humans perform tasks together, they may reach a higher performance in
comparison to the best member of a group (i.e., a collective benefit). Earlier
research showed that interindividual performance similarities predict collective
benefits for several joint tasks. Yet, researchers did not test whether this is
the case for joint visuospatial tasks. Also, researchers did not investigate
whether dyads and triads reach a collective benefit when they are forbidden to
exchange any information while performing a visuospatial task. In this study,
participants performed a joint visual search task either alone, in dyads, or in
triads, and were not allowed to exchange any information while doing the task. We
found that dyads reached a collective benefit. Triads did outperform their best
individual member and dyads-yet, they did not outperform the best dyad pairing
within the triad. In addition, similarities in performance significantly
predicted the collective benefit for dyads and triads. Furthermore, we find that
the dyads' and triads' search performances closely match a simulated performance
based on the individual search performances, which assumed that members of a
group act independently. Overall, the present study supports the view that
performance similarities predict collective benefits in joint tasks. Moreover, it
provides a basis for future studies to investigate the benefits of exchanging
information between co-actors in joint visual search tasks.
PMID- 29329332
TI - Co-delivery of a laminin-111 supplemented hyaluronic acid based hydrogel with
minced muscle graft in the treatment of volumetric muscle loss injury.
AB - Minced muscle autografting mediates de novo myofiber regeneration and promotes
partial recovery of neuromuscular strength after volumetric muscle loss injury
(VML). A major limitation of this approach is the availability of sufficient
donor tissue for the treatment of relatively large VMLs without inducing donor
site morbidity. This study evaluated a laminin-111 supplemented hyaluronic acid
based hydrogel (HA+LMN) as a putative myoconductive scaffolding to be co
delivered with minced muscle grafts. In a rat tibialis anterior muscle VML model,
delivery of a reduced dose of minced muscle graft (50% of VML defect) within
HA+LMN resulted in a 42% improvement of peak tetanic torque production over
unrepaired VML affected limbs. However, the improvement in strength was not
improved compared to a 50% minced graft-only control group. Moreover,
histological analysis revealed that the improvement in in vivo functional
capacity mediated by minced grafts in HA+LMN was not accompanied by a
particularly robust graft mediated regenerative response as determined through
donor cell tracking of the GFP+ grafting material. Characterization of the
spatial distribution and density of macrophage and satellite cell populations
indicated that the combination therapy damps the heightened macrophage response
while re-establishing satellite content 14 days after VML to a level consistent
with an endogenously healing ischemia-reperfusion induced muscle injury.
Moreover, regional analysis revealed that the combination therapy increased
satellite cell density mostly in the remaining musculature, as opposed to the
defect area. Based on the results, the following salient conclusions were drawn:
1) functional recovery mediated by the combination therapy is likely due to a
superposition of de novo muscle fiber regeneration and augmented repair of muscle
fibers within the remaining musculature, and 2) The capacity for VML therapies to
augment regeneration and repair within the remaining musculature may have
significant clinical impact and warrants further exploration.
PMID- 29329334
TI - Ensemble learning method for the prediction of new bioactive molecules.
AB - Pharmacologically active molecules can provide remedies for a range of different
illnesses and infections. Therefore, the search for such bioactive molecules has
been an enduring mission. As such, there is a need to employ a more suitable,
reliable, and robust classification method for enhancing the prediction of the
existence of new bioactive molecules. In this paper, we adopt a recently
developed combination of different boosting methods (Adaboost) for the prediction
of new bioactive molecules. We conducted the research experiments utilizing the
widely used MDL Drug Data Report (MDDR) database. The proposed boosting method
generated better results than other machine learning methods. This finding
suggests that the method is suitable for inclusion among the in silico tools for
use in cheminformatics, computational chemistry and molecular biology.
PMID- 29329333
TI - Wide-range screening of anti-inflammatory compounds in tomato using LC-MS and
elucidating the mechanism of their functions.
AB - Obesity-induced chronic inflammation is a key factor in type 2 diabetes. A
vicious cycle involving pro-inflammatory mediators between adipocytes and
macrophages is a common cause of chronic inflammation in the adipose tissue.
Tomato is one of the most popular vegetables and is associated with a reduced
risk of diabetes. However, the molecular mechanism underlying the effect of
tomato on diabetes is unclear. In this study, we focused on anti-inflammatory
compounds in tomato. We found that the extract of tomato reduced plasma glucose
and inflammatory markers in mice. We screened anti-inflammatory fractions in
tomato using lipopolysaccharide-stimulated RAW264.7 macrophages, and active
compounds were estimated by liquid chromatography-mass spectrometry over a wide
range. Surprisingly, a large number of compounds including oxylipin and coumarin
derivatives were estimated as anti-inflammatory compounds. Especially, 9-oxo
octadecadienoic acid and daphnetin suppressed pro-inflammatory cytokines in
RAW264.7 macrophages inhibiting mitogen-activated protein kinase phosphorylation
and inhibitor of kappa B alpha protein degradation. These findings suggest that
tomato containing diverse anti-inflammatory compounds ameliorates chronic
inflammation in obese adipose tissue.
PMID- 29329336
TI - Effective dispersal and density-dependence in mesophotic macroalgal forests:
Insights from the Mediterranean species Cystoseira zosteroides.
AB - Dispersal and recruitment are fundamental processes for population recovery
following disturbances in sessile species. While both processes are well
understood for many terrestrial species, they still remain poorly resolved for
some macroalgal species. Here we experimentally investigated the effective
dispersal and recruit survival of a mesophotic Mediterranean fucoid, Cystoseira
zosteroides. In three isolated populations, four sets of settlement collectors
were placed at increasing distances (from 0 to 10 m) and different orientations
(North, South, East and West). We observed that effective dispersal was
restricted to populations' vicinity, with an average of 6.43 m and not further
than 13.33 m, following a Weibull distribution. During their first year of life,
survival was up to 50%, but it was lower underneath the adult canopy, suggesting
a negative density-dependence. To put our results in a broader context we
compared the effective dispersal of other fucoid and kelp species reported in the
literature, which confirmed the low dispersal ability of brown algae, in
particular for fucoids, with an effective dispersal of few meters. Given the
importance of recruitment for the persistence and recovery of populations after
disturbances, these results underline the vulnerability of C. zosteroides and
other fucoid species to escalating threats.
PMID- 29329335
TI - Immunization with gingipain A hemagglutinin domain of Porphyromonas gingivalis
induces IgM antibodies binding to malondialdehyde-acetaldehyde modified low
density lipoprotein.
AB - Treatment of periodontitis has beneficial effects on systemic inflammation
markers that relate to progression of atherosclerosis. We aimed to investigate
whether immunization with A hemagglutinin domain (Rgp44) of Porphyromonas
gingivalis (Pg), a major etiologic agent of periodontitis, would lead to an
antibody response cross-reacting with oxidized low-density lipoprotein (OxLDL)
and how it would affect the progression of atherosclerosis in low-density
lipoprotein receptor-deficient (LDLR-/-) mice. The data revealed a prominent IgM
but not IgG response to malondialdehyde-acetaldehyde modified LDL (MAA-LDL) after
Rgp44 and Pg immunizations, implying that Rgp44/Pg and MAA adducts may share
cross-reactive epitopes that prompt IgM antibody production and consequently
confer atheroprotection. A significant negative association was observed between
atherosclerotic lesion and plasma IgA to Rgp44 in Rgp44 immunized mice,
supporting further the anti-atherogenic effect of Rgp44 immunization. Plasma IgA
levels to Rgp44 and to Pg in both Rgp44- and Pg-immunized mice were significantly
higher than those in saline control, suggesting that IgA to Rgp44 could be a
surrogate marker of immunization in Pg-immunized mice. Distinct antibody
responses in plasma IgA levels to MAA-LDL, to Pg lipopolysaccharides (Pg-LPS),
and to phosphocholine (PCho) were observed after Rgp44 and Pg immunizations,
indicating that different immunogenic components between Rpg44 and Pg may behave
differently in regard of their roles in the development of atherosclerosis.
Immunization with Rgp44 also displayed atheroprotective features in modulation of
plaque size through association with plasma levels of IL-1alpha whereas whole Pg
bacteria achieved through regulation of anti-inflammatory cytokine levels of IL-5
and IL-10. The present study may contribute to refining therapeutic approaches
aiming to modulate immune responses and inflammatory/anti-inflammatory processes
in atherosclerosis.
PMID- 29329337
TI - Mitochondrial DNA ancestry, HPV infection and the risk of cervical cancer in a
multiethnic population of northeastern Argentina.
AB - BACKGROUND: Misiones Province in northeastern Argentina is considered to be a
region with a high prevalence of HPV infection and a high mortality rate due to
cervical cancer. The reasons for this epidemiological trend are not completely
understood. To gain insight into this problem, we explored the relationship
between mitochondrial DNA (mtDNA) ancestry, HPV infection, and development of
cervical lesions/cancer in women from the city of Posadas in Misiones Province.
METHODS: Two hundred and sixty-one women, including 92 cases of patients
diagnosed with cervical lesions and 169 controls, were analyzed. mtDNA ancestry
was assessed through HVS1 sequencing, while the detection and typing of HPV
infection was conducted through nested multiplex PCR analysis. Multivariate
logistic regression was conducted with the resulting data to estimate the odds
ratios (ORs) adjusted by socio-demographic variables. RESULTS: The study
participants showed 68.6% Amerindian, 26.1% European and 5.3% African mtDNA
ancestry, respectively. Multiple regression analysis showed that women with
African mtDNAs were three times more likely to develop a cervical lesion than
those with Native American or European mtDNAs [OR of 3.8 (1.2-11.5) for ancestry
and OR of 3.5 (1.0-12.0) for L haplogroups], although the associated p values
were not significant when tested under more complex multivariate models. HPV
infection and the development of cervical lesions/cancer were significant for all
tested models, with the highest OR values for HPV16 [OR of 24.2 (9.3-62.7)] and
HPV-58 [OR of 19.0 (2.4-147.7)]. CONCLUSION: HPV infection remains a central risk
factor for cervical cancer in the Posadas population. The potential role of
African mtDNA ancestry opens a new avenue for future medical association studies
in multiethnic populations, and will require further confirmation in large-scale
studies.
PMID- 29329338
TI - Pharmacoepidemiological assessment of adherence and influencing co-factors among
primary open-angle glaucoma patients-An observational cohort study.
AB - The goal of this study was to assess the adherence of primary open-angle glaucoma
(POAG) patients to medication, and to determine co-factors influencing adherence,
using a representative sample of members of the largest German public health
insurer. The observational cohort study was based on a longitudinal data set from
2010-2013 and included 250,000 insured persons aged 50 and older with 10,120
diagnosed POAG patients. Uni- and multivariate analysis was performed to
investigate several aspects of glaucoma, such as prevalence, adherence, and co
factors influencing adherence. The main outcome measured adherence with
prescriptions filled within a year. Multivariate panel regression analysis was
used to determine the co-factors influencing this adherence. Prevalence of POAG
was 3.36% [CI: 3.28-3.43%], with 2.91% [CI: 2.81-3.01%] for males and 3.71% [CI:
3.61-3.81%] for females, increasing with age. The mean level of adherence in
terms of prescriptions filled was 66.5% [CI: 65.50-67.60%]. The results of this
analysis revealed a significant influence of age, duration of the disease, care
need, distance to death, and multimorbidity as co-factors of non-adherence,
whereas gender had no influence. The analysis provided detailed information about
POAG health care aspects concerning prevalence and adherence. The most endangered
risk groups for non-adherence were patients aged 50-59, patients older than 80
years, patients with a longer duration of POAG, patients with care needs, and
patients with three or more severe diseases in addition to glaucoma. To know the
predictors responsible for an increased risk to develop POAG is of importance for
all persons involved in health care management. Therefore effective strategies to
increase awareness of patients and medical care personnel about non-adherence and
the importance of a regular and continuous medication to avoid further nerve
fiber damage and possible blindness have to be developed.
PMID- 29329341
TI - Correction: A century of changing flows: Forest management changed flow
magnitudes and warming advanced the timing of flow in a southwestern US river.
AB - [This corrects the article DOI: 10.1371/journal.pone.0187875.].
PMID- 29329340
TI - Cognitive control moderates parenting stress effects on children's diurnal
cortisol.
AB - This study investigated associations between parenting stress in parents and self
reported stress in children with children's diurnal cortisol secretion and
whether these associations are moderated by known stress-regulating capacities,
namely child cognitive control. Salivary cortisol concentrations were assessed
from awakening to evening on two weekend days from 53 6-to-7-year-old children.
Children completed a cognitive control task and a self-report stress
questionnaire with an experimenter, while parents completed a parenting stress
inventory. Hierarchical, linear mixed effects models revealed that higher
parenting stress was associated with overall reduced cortisol secretion in
children, and this effect was moderated by cognitive control. Specifically,
parenting stress was associated with reduced diurnal cortisol levels in children
with lower cognitive control ability and not in children with higher cognitive
control ability. There were no effects of self-reported stress in children on
their cortisol secretion, presumably because 6-to-7-year-old children cannot yet
self-report on stress experiences. Our results suggest that higher cognitive
control skills may buffer the effects of parenting stress in parents on their
children's stress regulation in middle childhood. This could indicate that
training cognitive control skills in early life could be a target to prevent
stress-related disorders.
PMID- 29329339
TI - Accessibility and contribution to glucan masking of natural and genetically
tagged versions of yeast wall protein 1 of Candida albicans.
AB - Yeast wall protein 1 (Ywp1) is an abundant glycoprotein of the cell wall of the
yeast form of Candida albicans, the most prevalent fungal pathogen of humans.
Antibodies that bind to the polypeptide backbone of isolated Ywp1 show little
binding to intact yeast cells, presumably because the Ywp1 epitopes are masked by
the polysaccharides of the mannoproteins that form the outer layer of the cell
wall. Rare cells do exhibit much greater anti-Ywp1 binding, however, and one of
these was isolated and characterized. No differences were seen in its Ywp1, but
it exhibited greater adhesiveness, sensitivity to wall perturbing agents, and
exposure of its underlying beta-1,3-glucan layer to external antibodies. The
molecular basis for this greater epitope accessibility has not been determined,
but has facilitated exploration of how these properties change as a function of
cell growth and morphology. In addition, previously engineered strains with
reduced quantities of Ywp1 in their cell walls were also found to have greater
beta-1,3-glucan exposure, indicating that Ywp1 itself contributes to the masking
of wall epitopes, which may be important for understanding the anti-adhesive
effect of Ywp1. Ectopic production of Ywp1 by hyphae, which reduces the
adhesivity of these filamentous forms of C. albicans, was similarly found to
reduce exposure of the beta-1,3-glucan in their walls. To monitor Ywp1 in the
cell wall irrespective of its accessibility, green fluorescent protein (Gfp) was
genetically inserted into wall-anchored Ywp1 using a bifunctional cassette that
also allowed production from a single transfection of a soluble, anchor-free
version. The wall-anchored Ywp1-Gfp-Ywp1 accumulated in the wall of the yeast
forms but not hyphae, and appeared to have properties similar to native Ywp1,
including its adhesion-inhibiting effect. Some pseudohyphal walls also detectably
accumulated this probe. Strains of C. albicans with tandem hemagglutinin (HA)
epitopes inserted into wall-anchored Ywp1 were previously created by others, and
were further explored here. As above, rare cells with much greater accessibility
of the HA epitopes were isolated, and also found to exhibit greater exposure of
Ywp1 and beta-1,3-glucan. The placement of the HA cassette inhibited the normal N
glycosylation and propeptide cleavage of Ywp1, but the wall-anchored Ywp1-HA-Ywp1
still accumulated in the cell wall of yeast forms. Bifunctional transformation
cassettes were used to additionally tag these molecules with Gfp, generating
soluble Ywp1-HA-Gfp and wall-anchored Ywp1-HA-Gfp-Ywp1 molecules. The former
revealed unexpected electrophoretic properties caused by the HA insertion, while
the latter further highlighted differences between the presence of a tagged Ywp1
molecule (as revealed by Gfp fluorescence) and its accessibility in the cell wall
to externally applied antibodies specific for HA, Gfp and Ywp1, with
accessibility being greatest in the rapidly expanding walls of budding daughter
cells. These strains and results increase our understanding of cell wall
properties and how C. albicans masks itself from recognition by the human immune
system.
PMID- 29329342
TI - Ternary copper(II) complex: NCI60 screening, toxicity studies, and evaluation of
efficacy in xenograft models of nasopharyngeal carcinoma.
AB - Copper(II) ternary complex, [Cu(phen)(C-dmg)(H2O)]NO3 was evaluated against a
panel of cell lines, tested for in vivo efficacy in nasopharyngeal carcinoma
xenograft models as well as for toxicity in NOD scid gamma mice. The Cu(II)
complex displayed broad spectrum cytotoxicity against multiple cancer types,
including lung, colon, central nervous system, melanoma, ovarian, and prostate
cancer cell lines in the NCI-60 panel. The Cu(II) complex did not cause
significant induction of cytochrome P450 (CYP) 3A and 1A enzymes but moderately
inhibited CYP isoforms 1A2, 2C9, 2C19, 2D6, 2B6, 2C8 and 3A4. The complex
significantly inhibited tumor growth in nasopharyngeal carcinoma xenograft
bearing mice models at doses which were well tolerated without causing
significant or permanent toxic side effects. However, higher doses which resulted
in better inhibition of tumor growth also resulted in toxicity.
PMID- 29329343
TI - Effect of freeze-thaw cycling on grain size of biochar.
AB - Biochar may improve soil hydrology by altering soil porosity, density, hydraulic
conductivity, and water-holding capacity. These properties are associated with
the grain size distributions of both soil and biochar, and therefore may change
as biochar weathers. Here we report how freeze-thaw (F-T) cycling impacts the
grain size of pine, mesquite, miscanthus, and sewage waste biochars under two
drainage conditions: undrained (all biochars) and a gravity-drained experiment
(mesquite biochar only). In the undrained experiment plant biochars showed a
decrease in median grain size and a change in grain-size distribution consistent
with the flaking off of thin layers from the biochar surface. Biochar grain size
distribution changed from unimodal to bimodal, with lower peaks and wider
distributions. For plant biochars the median grain size decreased by up to 45.8%
and the grain aspect ratio increased by up to 22.4% after 20 F-T cycles. F-T
cycling did not change the grain size or aspect ratio of sewage waste biochar. We
also observed changes in the skeletal density of biochars (maximum increase of
1.3%), envelope density (maximum decrease of 12.2%), and intraporosity (porosity
inside particles, maximum increase of 3.2%). In the drained experiment, mesquite
biochar exhibited a decrease of median grain size (up to 4.2%) and no change of
aspect ratio after 10 F-T cycles. We also document a positive relationship
between grain size decrease and initial water content, suggesting that, biochar
properties that increase water content, like high intraporosity and pore
connectivity large intrapores, and hydrophilicity, combined with undrained
conditions and frequent F-T cycles may increase biochar breakdown. The observed
changes in biochar particle size and shape can be expected to alter hydrologic
properties, and thus may impact both plant growth and the hydrologic cycle.
PMID- 29329344
TI - Maintenance of muscle strength retains a normal metabolic cost in simulated
walking after transtibial limb loss.
AB - Recent studies on relatively young and fit individuals with limb loss suggest
that maintaining muscle strength after limb loss may mitigate the high metabolic
cost of walking typically seen in the larger general limb loss population.
However, these data are cross-sectional and the muscle strength prior to limb
loss is unknown, and it is therefore difficult to draw causal inferences on
changes in strength and gait energetics. Here we used musculoskeletal modeling
and optimal control simulations to perform a longitudinal study (25 virtual
"subjects") of the metabolic cost of walking pre- and post-limb loss (unilateral
transtibial). Simulations of walking were first performed pre-limb loss on a
model with two intact biological legs, then post-limb loss on a model with a
unilateral transtibial prosthesis, with a cost function that minimized the
weighted sum of gait deviations plus metabolic cost. Metabolic costs were
compared pre- vs. post-limb loss, with systematic modifications to the muscle
strength and prosthesis type (passive, powered) in the post-limb loss model. The
metabolic cost prior to limb loss was 3.44+/-0.13 J/m/kg. After limb loss, with a
passive prosthesis the metabolic cost did not increase above the pre-limb loss
cost if pre-limb loss muscle strength was maintained (mean -0.6%, p = 0.17, d =
0.17). With 10% strength loss the metabolic cost with the passive prosthesis
increased (mean +5.9%, p < 0.001, d = 1.61). With a powered prosthesis, the
metabolic cost was at or below the pre-limb loss cost for all subjects with
strength losses of 10% and 20%, but increased for all subjects with strength loss
of 30% (mean +5.9%, p < 0.001, d = 1.59). The results suggest that maintaining
muscle strength may prevent an increase in the metabolic cost of walking
following unilateral transtibial limb loss, and that a gait with minimal
deviations can be achieved when muscle strength is sufficiently high, even when
using a passive prosthesis.
PMID- 29329345
TI - Survival benefit associated with metformin use in inoperable non-small cell lung
cancer patients with diabetes: A population-based retrospective cohort study.
AB - OBJECTIVE: To evaluate the effects of metformin use on the survival of inoperable
non-small cell lung cancer (NSCLC) patients with diabetes using the Taiwanese
National Health Insurance Research Database. RESEARCH DESIGN AND METHODS: In
total, 7,620 patients were eligible in this study, among them, 3,578 patients
were metformin users and 4,042 were non-users. Propensity score matching was used
to reduce possible confounding factors. In total, 4,182 patients (2,091 matched
pairs) were included in the matched cohort. Cox proportional hazard model with
time-dependent covariate were also applied to evaluate the association between
metformin use and overall survival (OS). RESULTS: A total of 3,578 patients were
metformin users at the time of diagnosis of NSCLC. Cox proportional hazard model
with time-dependent covariate revealed that metformin use was associated with a
significantly longer OS (HR: 0.85, 95.0% CI: 0.80-0.90). The survival benefit of
metformin use was maintained after propensity score matching at a ratio of 1:1
(HR: 0.90, 95.0% CI: 0.84-0.97). CONCLUSIONS: Metformin use is associated with
longer OS in inoperable NSCLC patients with diabetes, suggesting a potential anti
tumorigenic effect for metformin. Further research is needed to investigate the
actual role of metformin in the treatment of NSCLC patients with diabetes.
PMID- 29329346
TI - Evaluation of bloodstream infections, Clostridium difficile infections, and gut
microbiota in pediatric oncology patients.
AB - Bloodstream infections (BSI) and Clostridium difficile infections (CDI) in
pediatric oncology/hematology/bone marrow transplant (BMT) populations are
associated with significant morbidity and mortality. The objective of this study
was to explore possible associations between altered microbiome composition and
the occurrence of BSI and CDI in a cohort of pediatric oncology patients. Stool
samples were collected from all patients admitted to the pediatric oncology floor
from Oct.-Dec. 2012. Bacterial profiles from patient stools were determined by
bacterial 16S rRNA gene profiling. Differences in overall microbiome composition
were assessed by a permutation-based multivariate analysis of variance test,
while differences in the relative abundances of specific taxa were assessed by
Kruskal-Wallis tests. At admission, 9 of 42 patients (21%) were colonized with C.
difficile, while 6 of 42 (14%) subsequently developed a CDI. Furthermore, 3
patients (7%) previously had a BSI and 6 patients (14%) subsequently developed a
BSI. Differences in overall microbiome composition were significantly associated
with disease type (p = 0.0086), chemotherapy treatment (p = 0.018), BSI following
admission from any cause (p < 0.0001) or suspected gastrointestinal organisms (p
= 0.00043). No differences in baseline microbiota were observed between
individuals who did or did not subsequently develop C. difficile infection.
Additionally, multiple bacterial groups varied significantly between subjects
with post-admission BSI compared with no BSI. Our results suggest that
differences in gut microbiota not only are associated with type of cancer and
chemotherapy, but may also be predictive of subsequent bloodstream infection.
PMID- 29329348
TI - Correction: Risk of thromboembolism in cisplatin versus carboplatin-treated
patients with lung cancer.
AB - [This corrects the article DOI: 10.1371/journal.pone.0189410.].
PMID- 29329347
TI - Salivary proteomics of healthy dogs: An in depth catalog.
AB - OBJECTIVE: To provide an in-depth catalog of the salivary proteome and endogenous
peptidome of healthy dogs, evaluate proteins and peptides with antimicrobial
properties, and compare the most common salivary proteins and peptides between
different breed phylogeny groups. METHODS: 36 healthy dogs without evidence of
periodontal disease representing four breed phylogeny groups, based upon single
nucleotide polymorphism haplotypes (ancient, herding/sighthound, and two
miscellaneous groups). Saliva collected from dogs was pooled by phylogeny group
and analyzed using nanoscale liquid chromatography-tandem mass spectrometry.
Resulting tandem mass spectra were compared to databases for identification of
endogenous peptides and inferred proteins. RESULTS: 2,491 proteins and endogenous
peptides were found in the saliva of healthy dogs with no periodontal disease.
All dog phylogeny groups' saliva was rich in proteins and peptides with
antimicrobial functions. The ancient breeds group was distinct in that it
contained unique proteins and was missing many proteins and peptides present in
the other groups. CONCLUSIONS AND CLINICAL RELEVANCE: Using a sophisticated
nanoscale liquid chromatography-tandem mass spectrometry, we were able to
identify 10-fold more salivary proteins than previously reported in dogs. Seven
of the top 10 most abundant proteins or peptides serve immune functions and many
more with various antimicrobial mechanisms were found. This is the most
comprehensive analysis of healthy canine saliva to date, and will provide the
groundwork for future studies analyzing salivary proteins and endogenous peptides
in disease states.
PMID- 29329349
TI - Natural wind variability triggered drop in German redispatch volume and costs
from 2015 to 2016.
AB - Avoiding dangerous climate change necessitates the decarbonization of electricity
systems within the next few decades. In Germany, this decarbonization is based on
an increased exploitation of variable renewable electricity sources such as wind
and solar power. While system security has remained constantly high, the
integration of renewables causes additional costs. In 2015, the costs of grid
management saw an all time high of about ? 1 billion. Despite the addition of
renewable capacity, these costs dropped substantially in 2016. We thus
investigate the effect of natural climate variability on grid management costs in
this study. We show that the decline is triggered by natural wind variability
focusing on redispatch as a main cost driver. In particular, we find that 2016
was a weak year in terms of wind generation averages and the occurrence of
westerly circulation weather types. Moreover, we show that a simple model based
on the wind generation time series is skillful in detecting redispatch events on
timescales of weeks and beyond. As a consequence, alterations in annual
redispatch costs in the order of hundreds of millions of euros need to be
understood and communicated as a normal feature of the current system due to
natural wind variability.
PMID- 29329350
TI - Incidence and risk factors for postoperative lingual neuropraxia following airway
instrumentation: A retrospective matched case-control study.
AB - BACKGROUND: Lingual nerve injury or neuropraxia is a rare but potentially serious
perioperative complication following airway instrumentation during general
anesthesia. This study explored the the incidence and perioperative risk factors
for lingual nerve injury in patients receiving laryngeal mask (LMA) or
endotracheal (ETGA) general anesthesia in a single center experience. METHODS AND
RESULTS: All surgical patients in our hospital who received LMA or ETGA from 2009
to 2013 were included, and potential perioperative risk factors were compared.
Matched controls were randomly selected (in 1:5 ratio) from the same database in
non-case patients. A total of 36 patients in the records had reported
experiencing tongue numbness after anesthesia in this study. Compared with the
non-case surgical population (n = 54314), patients with tongue numbness were
significantly younger (52.2+/-19.5 vs 42.0+/-14.5; P = 0.002) and reported lower
ASA physical statuses (2.3+/-0.7 vs 1.6+/-0.6; P<0.001). Patient gender,
anesthesia technique used, and airway device type (LMA or ETGA) did not differ
significantly across the two groups. A significantly higher proportion of
patients underwent operations of the head-and-neck region (38.9 vs 15.6%; P =
0.002) developed tongue numbness after anesthesia. Multivariate logistic
regression analysis indicated that head-and-neck operations remained the most
significant independent risk factor for postoperative lingual nerve injury (AOR
7.63; 95% CI 2.03-28.70). CONCLUSION: The overall incidence rate of postoperative
lingual neuropraxy was 0.066% in patients receiving general anesthesia with
airway device in place. Young and generally healthy patients receiving head-and
neck operation are at higher risk in developing postoperative lingual neuropraxy.
Attention should be particularly exercised to reduce the pressure of endotracheal
tube or laryngeal mask on the tongue during head-and-neck operation to avert the
occurrence of postoperative lingual neuropraxy.
PMID- 29329351
TI - Educational gradients in the use of electronic cigarettes and heat-not-burn
tobacco products in Japan.
AB - OBJECTIVES: In addition to electronic cigarettes (e-cigarettes), tobacco
companies have recently begun to sell heat-not-burn tobacco products, Ploom and
iQOS in Japan. Previous research has reported an inverse association between
combustible cigarette smoking and educational attainment, but little is known
about the association for e-cigarettes, especially heat-not-burn tobacco
products. Our objective was to analyze the relationship between educational
attainment and e-cigarette and heat-not-burn tobacco use. SETTING: An internet
survey (randomly sampled research agency panelists) in Japan. PARTICIPANTS: A
total of 7338 respondents aged 18-69 years in 2015 (3632 men and 3706women).
PRIMARY MEASURES: Adjusted odds ratios (ORs) of educational attainment for
current smoking (combustible cigarettes), e-cigarette ever-use, and heat-not-burn
ever-use were calculated by multivariable logistic regression models using
covariates including socio-demographic factors. Stratified analyses according to
smoking status (combustible cigarettes) were additionally performed for e
cigarette ever-use and heat-not-burn tobacco product ever-use. RESULTS:
Associations between educational attainment and e-cigarette ever-use or heat-not
burn tobacco ever-use are not straightforward, although these associations are
not statistically significant except for one cell. For example, using "graduate
school" education as a reference category, adjusted ORs for "high school" were
1.44 (95% confidence interval [CI]: 0.85-2.44) for e-cigarettes ever-use and 0.75
(95% CI:0.19-2.97) for heat-not-burn tobacco product ever-use. Among current
smokers, compared with "graduate school" (reference), those with lower
educational attainment showed 0.6 to 0.7 ORs for e-cigarette ever-use: e.g.,"4
year university"(OR = 0.54, 95% CI:0.24-1.24) and "high school" (OR = 0.69, 95%
CI: 0.30-1.60). Among former smokers, lower education indicated higher ORs for
both e-cigarettes and heat-not-burn tobacco ever-use. CONCLUSIONS: This study
provides baseline information on educational gradients of e-cigarette and heat
not-burn tobacco products, ever-use. As heat-not-burn tobacco products are
increasing their market share in Japan, continuous monitoring of these products
will be necessary.
PMID- 29329353
TI - Estimating the responses of winter wheat yields to moisture variations in the
past 35 years in Jiangsu Province of China.
AB - Jiangsu is an important agricultural province in China. Winter wheat, as the
second major grain crop in the province, is greatly affected by moisture
variations. The objective of this study was to investigate whether there were
significant trends in changes in the moisture conditions during wheat growing
seasons over the past decades and how the wheat yields responded to different
moisture levels by means of a popular drought index, the Standardized
Precipitation Evapotranspiration Index (SPEI). The study started with a trend
analysis and quantification of the moisture conditions with the Mann-Kendall test
and Sen's Slope method, respectively. Then, correlation analysis was carried out
to determine the relationship between de-trended wheat yields and multi-scalar
SPEI. Finally, a multivariate panel regression model was established to reveal
the quantitative yield responses to moisture variations. The results showed that
the moisture conditions in Jiangsu were generally at a normal level, but this
century appeared slightly drier in because of the relatively high temperatures.
There was a significant correlation between short time scale SPEI values and
wheat yields. Among the three critical stages of wheat development, the SPEI
values in the late growth stage (April-June) had a closer linkage to the yields
than in the seedling stage (October-November) and the over-wintering stage
(December-February). Moreover, the yield responses displayed an asymmetric
characteristic, namely, moisture excess led to higher yield losses compared to
moisture deficit in this region. The maximum yield increment could be obtained
under the moisture level of slight drought according to the 3-month SPEI at the
late growth stage, while extreme wetting resulted in the most severe yield
losses. The moisture conditions in the first 15 years of the 21st century were
more favorable than in the last 20 years of the 20th century for wheat production
in Jiangsu.
PMID- 29329352
TI - Interpersonal trauma moderates the relationship between personality factors and
suicidality of individuals with posttraumatic stress disorder.
AB - Individuals with posttraumatic stress disorder (PTSD) are more prone to suicidal
ideation and behavior. While those who have experienced interpersonal trauma
exhibit more suicidality than those who have experienced non-interpersonal
trauma, it is unclear how the traumatic effects are related to an individual's
personality characteristics. This study examined the association between
interpersonal trauma and personality factors with suicidality, and elucidated the
moderating role of interpersonal trauma in individuals with PTSD. The study
included 6,022 participants from the Korean Epidemiologic Catchment Area Study
2011. The Korean Version of Composite International Diagnostic Interview was used
for the survey, including the participants' history of suicidality, the traumas
they have experienced, and their PTSD symptoms. The 11-item version of the Big
Five Inventory (BFI-11) was used to assess the participants' personality factors.
76 individuals were diagnosed with PTSD, while 810 had been exposed to trauma but
were not diagnosed with any DSM-IV mental disorder. Among the individuals with
PTSD, those who had experienced interpersonal trauma were more likely to have
suicidal ideation than those who had experienced non-interpersonal trauma (p =
.020; odds ratio [OR] = 3.643; 95% confidence interval of OR = [1.226, 10.825]).
High agreeableness and conscientiousness predicted less suicidality in those
exposed to non-interpersonal trauma, while predicting more suicidality in those
exposed to interpersonal trauma. Clinicians examining individuals with PTSD
should pay closer attention to the trauma that they have experienced, as well as
their personality factors, to provide appropriate treatment.
PMID- 29329354
TI - Palmitate-induced ER stress and inhibition of protein synthesis in cultured
myotubes does not require Toll-like receptor 4.
AB - Saturated fatty acids, such as palmitate, are elevated in metabolically
dysfunctional conditions like type 2 diabetes mellitus. Palmitate has been shown
to impair insulin sensitivity and suppress protein synthesis while upregulating
proteolytic systems in skeletal muscle. Increased sarco/endoplasmic reticulum
(ER) stress and subsequent activation of the unfolded protein response may
contribute to the palmitate-induced impairment of muscle protein synthesis. In
some cell types, ER stress occurs through activation of the Toll-like receptor 4
(TLR4). Given the link between ER stress and suppression of protein synthesis, we
investigated whether palmitate induces markers of ER stress and protein synthesis
by activating TLR4 in cultured mouse C2C12 myotubes. Myotubes were treated with
vehicle, a TLR4-specific ligand (lipopolysaccharides), palmitate, or a
combination of palmitate plus a TLR4-specific inhibitor (TAK-242). Inflammatory
indicators of TLR4 activation (IL-6 and TNFalpha) and markers of ER stress were
measured, and protein synthesis was assessed using puromycin incorporation.
Palmitate substantially increased the levels of IL-6, TNF-alpha, CHOP, XBP1s, and
ATF 4 mRNAs and augmented the levels of CHOP, XBP1s, phospho-PERK and phospho
eIF2alpha proteins. The TLR4 antagonist attenuated both acute palmitate and LPS
induced increases in IL-6 and TNFalpha, but did not reduce ER stress signaling
with either 6 h or 24 h palmitate treatment. Similarly, treating myotubes with
palmitate for 6 h caused a 43% decline in protein synthesis consistent with an
increase in phospho-eIF2alpha, and the TLR4 antagonist did not alter these
responses. These results suggest that palmitate does not induce ER stress through
TLR4 in muscle, and that palmitate impairs protein synthesis in skeletal muscle
in part by induction of ER stress.
PMID- 29329357
TI - Mineralocorticoid Receptor Antagonists Treatment in Resistant Hypertension and
HFpEF: Evidence and Courage.
PMID- 29329356
TI - Prognostic factors of noninvasive mechanical ventilation in lung cancer patients
with acute respiratory failure.
AB - INTRODUCTION: Few studies have reported outcomes of lung cancer patients with
acute respiratory failure (RF) using noninvasive positive pressure ventilation
(NIPPV). The aim of this study was to investigate the prognostic factors in these
patients. MATERIALS AND METHODS: This retrospective observational study included
all hospitalized lung cancer patients who received NIPPV for acute RF. It was
conducted at a tertiary medical center in Taiwan from 2005 to 2010. The primary
outcome was all cause mortality at 28 days after the initiation of NIPPV.
Secondary outcomes included all-cause in-hospital mortality, weaning from NIPPV,
intubation rate, tracheostomy rate, duration of NIPPV, hospital stay and
intensive care unit stay. RESULTS: The all-cause mortality rate at day 28 of the
enrolled 58 patients was 39.66%. The 90-day and 1-year mortality rates were
63.79% and 86.21%, respectively. NIPPV as the first line therapy for RF had
higher 28-day mortality rate than it used for post-extubation RF (57.6% versus
16.0%, p<0.05). Independent predictors of mortality at 28 days were progressive
disease or newly diagnosed lung cancer (OR 14.02 95% CI 1.03-191.59, p = 0.048),
combined with other organ failure (OR 18.07 95% CI 1.87-172.7, p = 0.012), and
NIPPV as the first line therapy for RF (OR 35.37 95% CI 3.30-378.68, p = 0.003).
CONCLUSION: Lung cancer patients using NIPPV with progressive or newly diagnosed
cancer disease, combined with other organ failure, or NIPPV as the first line
therapy for respiratory failure have a poor outcome.
PMID- 29329355
TI - When the brain changes its mind: Oscillatory dynamics of conflict processing and
response switching in a flanker task during alcohol challenge.
AB - Despite the subjective experience of being in full and deliberate control of our
actions, our daily routines rely on a continuous and interactive engagement of
sensory evaluation and response preparation streams. They unfold automatically
and unconsciously and are seamlessly integrated with cognitive control which is
mobilized by stimuli that evoke ambiguity or response conflict. Methods with high
spatio-temporal sensitivity are needed to provide insight into the interplay
between automatic and controlled processing. This study used anatomically
constrained MEG to examine the underlying neural dynamics in a flanker task that
manipulated S-R incongruity at the stimulus (SI) and response levels (RI). Though
irrelevant, flankers evoked automatic preparation of motor plans which had to be
suppressed and reversed following the target presentation on RI trials. Event
related source power estimates in beta (15-25 Hz) frequency band in the
sensorimotor cortex tracked motor preparation and response in real time and
revealed switching from the incorrectly-primed to the correctly-responding
hemisphere. In contrast, theta oscillations (4-7 Hz) were sensitive to the levels
of incongruity as the medial and ventrolateral frontal cortices were especially
activated by response conflict. These two areas are key to cognitive control and
their integrated contributions to response inhibition and switching were revealed
by phase-locked co-oscillations. These processes were pharmacologically
manipulated with a moderate alcohol beverage or a placebo administered to healthy
social drinkers. Alcohol selectively decreased accuracy to response conflict. It
strongly attenuated theta oscillations during decision making and partly re
sculpted relative contributions of the frontal network without affecting the
motor switching process subserved by beta band. Our results indicate that motor
preparation is initiated automatically even when counterproductive but that it is
monitored and regulated by the prefrontal cognitive control processes under
conflict. They further confirm that the regulative top-down functions are
particularly vulnerable to alcohol intoxication.
PMID- 29329358
TI - Modulating Role of Ang1-7 in Control of Blood Pressure and Renal Function in
AngII-infused Hypertensive Rats.
AB - BACKGROUND: Indirect evidence suggests that angiotensin 1-7 (Ang1-7) may
counterbalance prohypertensive actions of angiotensin II (AngII), via activation
of vascular and/or renal tubular receptors to cause vasodilation and
natriuresis/diuresis. We examined if Ang1-7 would attenuate the development of
hypertension, renal vasoconstriction, and decreased natriuresis in AngII-infused
rats and evaluated the mechanisms involved. METHODS: AngII, alone or with Ang1-7,
was infused to conscious Sprague-Dawley rats for 13 days and systolic blood
pressure (SBP) and renal excretion were repeatedly determined. In anesthetized
rats, acute actions of Ang1-7 and effects of blockade of angiotensin AT1 or Mas
receptors (candesartan or A-779) were studied. RESULTS: Chronic AngII infusion
increased SBP from 143 +/- 4 to 195 +/- 6 mm Hg. With Ang1-7 co-infused, SBP
increased from 133 +/- 5 to 161 +/- 5 mm Hg (increase reduced, P < 0.002);
concurrent increases in urine flow (V) and sodium excretion (UNaV) were greater.
In anesthetized normotensive or AngII-induced hypertensive rats, Ang1-7 infusion
transiently increased mean arterial pressure (MABP), transiently decreased renal
blood flow (RBF), and caused increases in UNaV and V. In normotensive rats,
candesartan prevented the Ang1-7-induced increases in MABP and UNaV and the
decrease in RBF. In anesthetized normotensive, rats intravenous A-779 increased
MABP (114 +/- 5 to 120 +/- 5 mm Hg, P < 0.03) and urine flow. Surprisingly, these
changes were not observed with A-779 applied during background Ang1-7 infusion.
CONCLUSIONS: The results suggest that in AngII-dependent hypertension, Ang1-7
deficit contributes to sodium and fluid retention and thereby to BP elevation; a
correction by Ang1-7 infusion seems mediated by AT1 and not Mas receptors.
PMID- 29329360
TI - Tumor suppressor miR-128-3p inhibits metastasis and epithelial-mesenchymal
transition by targeting ZEB1 in esophageal squamous-cell cancer.
AB - MicroRNAs (miRNAs) are some short RNAs that regulate multiple biological
functions at post-transcriptional levels, such as tumorigenic processes,
inflammatory lesions and cell apoptosis. Zinc finger E-box binding homeobox
factor 1 (ZEB1) is a crucial mediator of epithelial-mesenchymal transition (EMT).
It induces malignant progression of various cancers including human esophageal
squamous-cell carcinoma (ESCC). In this study, we found that miR-128-3p was
downregulated in ESCC tissues and cells by using PCR. Moreover, down-regulated
expression of miR-128-3p was testified to be associated with poor prognosis of
ESCC patients and might be regarded as an independent prognostic factor. Then, we
examined the role of miR-128-3p in ESCC cells, and found that miR-128-3p could
suppress the cell migration and invasion in vitro. Furthermore, ZEB1 was
confirmed to be a direct target of miR-128-3p by luciferase reporter assay.
Rescue experiments proved that EMT was regulated by miR-128-3p via suppression of
ZEB1. Taken all together, we conclude that miR-128-3p suppresses EMT and
metastasis via ZEB1, and miR-128-3p may be a critical mediator in ESCC.
PMID- 29329359
TI - Effectiveness of Mass Media Campaigns to Reduce Alcohol Consumption and Harm: A
Systematic Review.
AB - Aims: To assess the effectiveness of mass media messages to reduce alcohol
consumption and related harms using a systematic literature review. Methods:
Eight databases were searched along with reference lists of eligible studies.
Studies of any design in any country were included, provided that they evaluated
a mass media intervention targeting alcohol consumption or related behavioural,
social cognitive or clinical outcomes. Drink driving interventions and college
campus campaigns were ineligible. Studies quality were assessed, data were
extracted and a narrative synthesis conducted. Results: Searches produced 10,212
results and 24 studies were included in the review. Most campaigns used TV or
radio in combination with other media channels were conducted in developed
countries and were of weak quality. There was little evidence of reductions in
alcohol consumption associated with exposure to campaigns based on 13 studies
which measured consumption, although most did not state this as a specific aim of
the campaign. There were some increases in treatment seeking and information
seeking and mixed evidence of changes in intentions, motivation, beliefs and
attitudes about alcohol. Campaigns were associated with increases in knowledge
about alcohol consumption, especially where levels had initially been low. Recall
of campaigns was high. Conclusion: Mass media health campaigns about alcohol are
often recalled by individuals, have achieved changes in knowledge, attitudes and
beliefs about alcohol but there is little evidence of reductions in alcohol
consumption. Short summary: There is little evidence that mass media campaigns
have reduced alcohol consumption although most did not state that they aimed to
do so. Studies show recall of campaigns is high and that they can have an impact
on knowledge, attitudes and beliefs about alcohol consumption.
PMID- 29329361
TI - pyHVis3D: visualising molecular simulation deduced H-bond networks in 3D:
application to T-cell receptor interactions.
AB - Motivation: Hydrogen bonds (H-bonds) play an essential role for many molecular
interactions but are also often transient, making visualising them in a flexible
system challenging. Results: We provide pyHVis3D which allows for an easy to
interpret 3D visualisation of H-bonds resulting from molecular simulations. We
demonstrate the power of pyHVis3D by using it to explain the changes in
experimentally measured binding affinities for three T-cell receptor/peptide/MHC
complexes and mutants of each of these complexes. Availability and
implementation: pyHVis3D can be downloaded for free from
http://opig.stats.ox.ac.uk/resources. Contact: science.bernhard.knapp@gmail.com.
Supplementary information: Supplementary data are available at Bioinformatics
online.
PMID- 29329362
TI - Clostridium butyricum regulates visceral hypersensitivity of irritable bowel
syndrome by inhibiting colonic mucous low grade inflammation through its action
on NLRP6.
AB - Visceral hypersensitivity induced by stress is quite common in irritable bowel
syndrome (IBS) patients. Probiotics play an important role in reducing visceral
hypersensitivity in IBS patients. However, the mechanism has not been clearly
elucidated. In this study, we investigated the role of nod-like receptor pyrin
domain-containing protein 6 (NLRP6) in Clostridium butyricum-regulated IBS
induced by stress. Our results showed that NLRP6 was down-regulated in IBS group
colon tissues. In addition, IL-18, IL-1beta, myeloperoxidase (MPO), d-lactic acid
(D-LA), and CD172a were up-regulated in the IBS group of colonic mucous. IL-18
and IL-1beta were also increased after the NLRP6 gene was silenced. Pathological
score suggested low inflammation of colonic mucous rather than terminal ileum.
Water-avoidance stress (WAS) showed visceral hypersensitivity to colonic
distension. However, treatment with Clostridium butyricum reversed these results,
exerting a beneficial effect. In conclusion, Clostridium butyricum may exert a
beneficial action on visceral hypersensitivity of IBS by inhibiting low grade
inflammation of colonic mucous through its action on NLRP6.
PMID- 29329363
TI - Validity of Teleneuropsychological Assessment in Older Patients with Cognitive
Disorders.
AB - Objective: The feasibility and reliability of neuropsychological assessment at a
distance have been demonstrated, but the validity of this testing medium has not
been adequately demonstrated. The purpose of this study was to determine the
ability of video teleconferencing administration of neuropsychological measures
(teleneuropsychology) in discriminating cognitively impaired from non-impaired
groups of older adults. It was predicted that measures administered via video
teleconference would distinguish groups and that the magnitude of differences
between impaired and non-impaired groups would be similar to group differences
achieved in traditional administration. Methods: The sample consisted of 197
older subjects, separated into two groups, with and without cognitive impairment.
The cognitive impairment group included 78 individuals with clinical diagnoses of
mild cognitive impairment or Alzheimer's disease. All participants completed
counterbalanced neuropsychological testing using alternate test forms in both a
teleneuropsychology and a traditional face-to-face (FTF) administration
condition. Tests were selected based upon their common use in dementia
evaluations, brevity, and assessment of multiple cognitive domains. Results from
FTF and teleneuropsychology test conditions were compared using individual
repeated measures ANCOVA, controlling for age, education, gender, and depression
scores. Results: All ANCOVA models revealed significant main effects of group and
a non-significant interaction between group and administration condition. All
ANCOVA models revealed non-significant main effects for administration condition,
except category fluency. Conclusions: Results derived from
teleneuropsychologically administered tests can distinguish between cognitively
impaired and non-impaired individuals similar to traditional FTF assessment. This
adds to the growing teleneuropsychology literature by supporting the validity of
remote assessments in aging populations.
PMID- 29329365
TI - A Formative Evaluation of Two FASD Prevention Communication Strategies.
AB - Aims: To evaluate the feasibility, acceptability and effectiveness of placing
FASD prevention messages in the women's restrooms of establishments serving
alcohol in Alaska and the Yukon, regions with high rates of FASD. Methods: Our
team placed an FASD educational poster, and posters affixed to a pregnancy test
dispenser, in women's restrooms of bars and restaurants. We compared drinking
behaviors and knowledge and beliefs about FASD among participants at baseline and
at follow-up. Results: Respondents consisted of 2132 women who completed a
baseline survey and 1182 women who completed both a baseline and a follow-up
survey. Women in both groups showed improvement in knowledge of FASD; the
dispenser group scored higher than participants in the poster group on the FASD
Health Belief questions at both baseline and follow-up. Forty-three women learned
they were pregnant from our pregnancy tests and alcohol consumption among
pregnant women was lower at follow-up than at baseline. Conclusions: FASD
prevention messages, particularly paired with pregnancy test dispensers, in the
women's restrooms of establishments that serve alcohol can effectively promote
informed alcohol consumption decisions among women who are, or may become,
pregnant. Short Summary: In this FASD prevention feasibility study, we found that
FASD prevention messages, particularly paired with pregnancy test dispensers,
placed in the women's restrooms of establishments that serve alcohol can
effectively promote informed alcohol consumption decisions among women who are,
or may become, pregnant.
PMID- 29329366
TI - Delineating differential regulatory signatures of the human transcriptome in the
choriodecidua and myometrium at term labor.
AB - Preterm deliveries remain the leading cause of neonatal morbidity and mortality.
Current therapies target only myometrial contractions and are largely
ineffective. As labor involves multiple coordinated events across maternal and
fetal tissues, identifying fundamental regulatory pathways of normal term labor
is vital to understanding successful parturition and consequently labor
pathologies. We aimed to identify transcriptomic signatures of human normal term
labor of two tissues: in the fetal-facing choriodecidua and the maternal
myometrium. Microarray transcriptomic data from choriodecidua and myometrium
following term labor were analyzed for functional hierarchical networks, using
Cytoscape 2.8.3. Hierarchically high candidates were analyzed for their
regulatory casual relationships using Ingenuity Pathway Analysis. Selected master
regulators were then chemically inhibited and effects on downstream targets were
assessed using real-time quantitative PCR (RT-qPCR). Unbiased network analysis
identified upstream molecular components in choriodecidua including vimentin,
TLR4, and TNFSF13B. In the myometrium, candidates included metallothionein 2
(MT2A), TLR2, and RELB. These master regulators had significant differential gene
expression during labor, hierarchically high centrality in community cluster
networks, interactions amongst the labor gene set, and strong causal
relationships with multiple downstream effects. In vitro experiments highlighted
MT2A as an effective regulator of labor-associated genes. We have identified
unique potential regulators of the term labor transcriptome in uterine tissues
using a robust sequence of unbiased mathematical and literature-based in silico
analyses. These findings encourage further investigation into the efficacy of
predicted master regulators in blocking multiple pathways of labor processes
across maternal and fetal tissues, and their potential as therapeutic approaches.
PMID- 29329364
TI - Downregulation of Drp1, a fission regulator, is associated with human lung and
colon cancers.
AB - Dynamin-related protein 1 (Drp1), a dynamin-related GTPase, is a key regulator of
mitochondrial fission. Although recent studies have shown that Drp1 plays
important roles in various important cellular processes, such as maintaining
proper mitochondrial function, apoptosis and necrosis, the potential involvement
of Drp1 in cancer development has not been fully addressed. To explore the role
of Drp1 in cancer, we examined Drp1 levels in various human cancer tissues.
Tissue array analysis showed that the level of Drp1 was decreased significantly
in malignant colon and lung cancer tissues, whereas no change in Drp1 was
observed in breast and prostate tumors. Pairwise comparisons of cancer tissue and
adjacent normal tissue from colon and lung cancer patients further confirmed
decreases in Drp1 expression of 75% in colon cancer patients and 78% in lung
cancer patients. Moreover, Drp1 levels were decreased further with advanced grade
in both colon and lung cancers, suggesting that loss of Drp1 is associated with
the progression of human lung and colon cancer. Consistent with this observation,
knockdown of Drp1 increased cellular migration activity in human lung cancer
cells and tumor formation in a xenograft tumor model. Taken together, these
results suggest that the loss of Drp1 expression could contribute to the
development of human lung and colon cancers.
PMID- 29329367
TI - Effects of Anodal Transcranial Direct Current Stimulation Over the Ventrolateral
Prefrontal Cortex on Episodic Memory Formation and Retrieval.
AB - In the past decade, several studies have investigated the effects of transcranial
direct current stimulation (tDCS) on episodic memory abilities. However, the
specific conditions under which tDCS affects memory remain largely unclear. Here,
we report data from 4 experiments aimed at investigating the effects of anodal
tDCS over the left ventrolateral prefrontal cortex (VLPFC) on verbal episodic
memory. We evaluated tDCS-induced effects as a function of time of
administration, nature of the memory encoding task, and age of the participants.
A robust enhancement of memory performance was only found when anodal tDCS was
delivered during intentional memorization. This enhancement was evident in young
and older adults. tDCS applied during incidental memorization or during retrieval
did not induce any modulation of memory performance, and memory was unaffected by
offline administration before encoding or retrieval. These results show that the
modulation of episodic memory functions by anodal tDCS over the left VLPFC is
dependent upon the time of administration and the nature of the memory task. The
findings may help profile the optimal stimulation protocols for
neurorehabilitation interventions on individuals with memory decline.
PMID- 29329368
TI - Discovering personalized driver mutation profiles of single samples in cancer by
network control strategy.
AB - Motivation: It is a challenging task to discover personalized driver genes that
provide crucial information on disease risk and drug sensitivity for individual
patients. However, few methods have been proposed to identify the personalized
sample driver genes from the cancer omics data due to the lack of samples for
each individual. To circumvent this problem, here we present a novel single
sample controller strategy (SCS) to identify personalized driver mutation
profiles from network controllability perspective. Results: SCS integrates
mutation data and expression data into a reference molecular network for each
patient to obtain the driver mutation profiles in a personalized-sample manner.
This is the first such a computational framework, to bridge the personalized
driver mutation discovery problem and the structural network controllability
problem. The key idea of SCS is to detect those mutated genes which can achieve
the transition from the normal state to the disease state based on each
individual omics data from network controllability perspective. We widely
validate the driver mutation profiles of our SCS from three aspects: (i) the
improved precision for the predicted driver genes in the population compared with
other driver-focus methods; (ii) the effectiveness for discovering the
personalized driver genes and (iii) the application to the risk assessment
through the integration of the driver mutation signature and expression data,
respectively, across the five distinct benchmarks from The Cancer Genome Atlas.
In conclusion, our SCS makes efficient and robust personalized driver mutation
profiles predictions, opening new avenues in personalized medicine and targeted
cancer therapy. Availability and implementation: The MATLAB-package for our SCS
is freely available from http://sysbio.sibcb.ac.cn/cb/chenlab/software.htm.
Contact: zhangsw@nwpu.edu.cn or zengtao@sibs.ac.cn or lnchen@sibs.ac.cn.
Supplementary information: Supplementary data are available at Bioinformatics
online.
PMID- 29329369
TI - A network approach to exploring the functional basis of gene-gene epistatic
interactions in disease susceptibility.
AB - Motivation: Individual genetic variants explain only a small fraction of
heritability in some diseases. Some variants have weak marginal effects on
disease risk, but their joint effects are significantly stronger when occurring
together. Most studies on such epistatic interactions have focused on methods for
identifying the interactions and interpreting individual cases, but few have
explored their general functional basis. This was due to the lack of a
comprehensive list of epistatic interactions and uncertainties in associating
variants to genes. Results: We conducted a large-scale survey of published
research articles to compile the first comprehensive list of epistatic
interactions in human diseases with detailed annotations. We used various methods
to associate these variants to genes to ensure robustness. We found that these
genes are significantly more connected in protein interaction networks, are more
co-expressed and participate more often in the same pathways. We demonstrate
using the list to discover novel disease pathways. Contact:
kevinyip@cse.cuhk.edu.hk. Supplementary information: Supplementary data are
available at Bioinformatics online.
PMID- 29329370
TI - Defining Normal Parameters for the Male Nipple-Areola Complex: A Prospective
Observational Study and Recommendations for Placement on the Chest Wall.
AB - Background: The nipple-areola complex (NAC) is important aesthetically and
functionally for both sexes. Methods for positioning the NAC in males are less
well established in the literature compared to females but are just as important.
Objectives: This study aims to determine the normal parameters for the male NAC,
to review literature, and to present a reliable method for preoperative
placement. Methods: Normal male patients, with no prior chest wall conditions,
were prospectively recruited to participate. General demographics and chest wall
dimensions were recorded-sternal notch to nipple (SNND), internipple (IND),
anterior axillary folds distances (AFD), NAC, and chest circumference were
measured. Comparisons were made using t test and ANOVA. Results: One hundred and
fifty-eight patients were recruited (age range, 18-90 years); mostly (86.7%) with
normal or overweight BMI. The IND averaged 249.4 mm, the SNND averaged 204.2 mm,
and the AFD averaged 383.8 mm. Areola diameter averaged 26.6 mm and for the
nipple, 6.9 mm. The IND:AFD ratio was 0.65. There was no statistical difference
in the IND:AFD ratio, SNND, or NAC parameters comparing different ethnic groups.
The SNND increased with greater BMI (P <= 0.001). Using these data, we suggest
ideal NAC dimensions and devised a simple method for positioning of the NAC on
the male chest wall. Conclusions: This is the largest study, with the widest
range in age and BMI, to date on this topic. Although fewer men than women
undergo surgery to the breast, there is a growing awareness for enhancing the
appearance of the male chest wall. Level of Evidence 4:
PMID- 29329372
TI - Enrichment analysis with EpiAnnotator.
AB - Motivation: Deciphering relevant biological insights from epigenomic data can be
a challenging task. One commonly used approach is to perform enrichment analysis.
However, finding, downloading and using the publicly available functional
annotations require time, programming skills and IT infrastructure. Here we
describe the online tool EpiAnnotator for performing enrichment analyses on
epigenomic data in a fast and user-friendly way. Results: EpiAnnotator is an R
Package accompanied by a web interface. It contains regularly updated annotations
from 4 public databases: Blueprint, RoadMap, GENCODE and the UCSC Genome Browser.
Annotations are hosted locally or in a server environment and automatically
updated by scripts of our own design. Thousands of tracks are available,
reflecting data on a variety of tissues, cell types and cell lines from the human
and mouse genomes. Users need to upload sets of selected and background regions.
Results are displayed in customizable and easily interpretable figures.
Availability and implementation: The R package and Shiny app are open source and
available under the GPL v3 license. EpiAnnotator's web interface is accessible at
http://computational-epigenomics.com/en/epiannotator. Contact:
epiannotator@computational-epigenomics.com.
PMID- 29329371
TI - Alcohol Use in Adolescence and Later Working Memory: Findings From a Large
Population-Based Birth Cohort.
AB - Aims: The study aimed to examine the association between adolescent alcohol use
and working memory (WM) using a large population sample. Methods: Data from the
Avon Longitudinal Study of Parents and Children were used to investigate the
association between alcohol use at age 15 years and WM 3 years later, assessed
using the N-back task (N ~ 3300). A three-category ordinal variable captured
mutually exclusive alcohol groupings ranging in order of severity (i.e. low
alcohol users, frequent drinkers and frequent/binge drinkers). Differential
dropout was accounted for using multiple imputation and inverse probability
weighting. Adjustment was made for potential confounders. Results: There was
evidence of an association between frequent/binge drinking (compared to the low
alcohol group) and poorer performance on the 3-back task after adjusting for
sociodemographic confounding variables, WM at age 11 years, and experience of a
head injury/unconsciousness before age 11 years (beta = -0.23, 95% CI = -0.37 to
0.09, P = 0.001). However, this association was attenuated (beta = -0.12, 95% CI
= -0.27 to 0.03, P = 0.11) when further adjusted for baseline measures of weekly
cigarette tobacco and cannabis use. Weaker associations were found for the less
demanding 2-back task. We found no evidence to suggest frequent drinking was
associated with performance on either task. Conclusions: We found weak evidence
of an association between sustained heavy alcohol use in mid-adolescence and
impaired WM 3 years later. Although we cannot fully rule out the possibility of
reverse causation, several potential confounding variables were included to
address the directionality of the relationship between WM and alcohol use
problems.
PMID- 29329374
TI - SimulaTE: simulating complex landscapes of transposable elements of populations.
PMID- 29329373
TI - Co-existing Hepatitis C and Alcoholic Liver Disease: A Diminishing Indication for
Liver Transplantation?
AB - Aims: To provide an overview of published literature on the interaction of
alcohol and hepatitis C virus (HCV) in the accelerated progression of liver
disease to cirrhosis as relates to decision-making for the management of the
liver transplant candidate and recipient. Methods: General PubMed search was
employed along with expert input to identify the relevant articles on the topic.
The authors also utilized both backward and forward citation review of the
relevant articles and reviews to identify articles on identified topic. Results:
In HCV cases, heavy alcohol use has been associated with more severe fibrosis,
but even low rates of use may have deleterious effects. Patients with chronic
hepatitis C and alcoholic liver disease can be cured of the HCV-theoretically
positively impacting outcome and reducing the need for liver transplantation.
Current antiviral therapy achieves virologic cure or sustained viral response
(SVR) in over 90% of cases. Antiviral therapy is so effective that most liver
transplant candidates or recipients can be cured of HCV either prior to or after
transplantation. However, despite successful antiviral therapy, liver disease may
progress after SVR due to the effects of ongoing alcohol use. Conclusion:
Antiviral therapy in patients with HCV plus alcohol should improve pre- and post
transplant outcomes, but providers must remain firm in limiting use of alcohol to
avoid progression of liver disease post HCV cure. Short Summary: Abusive alcohol
use and chronic hepatitis C virus (HCV) commonly co-exist and both need to be
addressed in liver disease. With high rates of HCV cure with new therapies,
attention needs to turn toward ongoing abusive alcohol patterns that may
determinately impact liver health both before and after liver transplant.
PMID- 29329375
TI - Heterogeneous Redistribution of Facial Subcategory Information Within and Outside
the Face-Selective Domain in Primate Inferior Temporal Cortex.
AB - The inferior temporal cortex (ITC) contains neurons selective to multiple levels
of visual categories. However, the mechanisms by which these neurons collectively
construct hierarchical category percepts remain unclear. By comparing decoding
accuracy with simultaneously acquired electrocorticogram (ECoG), local field
potentials (LFPs), and multi-unit activity in the macaque ITC, we show that low
frequency LFPs/ECoG in the early evoked visual response phase contain sufficient
coarse category (e.g., face) information, which is homogeneous and enhanced by
spatial summation of up to several millimeters. Late-induced high-frequency LFPs
additionally carry spike-coupled finer category (e.g., species, view, and
identity of the face) information, which is heterogeneous and reduced by spatial
summation. Face-encoding neural activity forms a cluster in similar cortical
locations regardless of whether it is defined by early evoked low-frequency
signals or late-induced high-gamma signals. By contrast, facial subcategory
encoding activity is distributed, not confined to the face cluster, and
dynamically increases its heterogeneity from the early evoked to late-induced
phases. These findings support a view that, in contrast to the homogeneous and
static coarse category-encoding neural cluster, finer category-encoding clusters
are heterogeneously distributed even outside their parent category cluster and
dynamically increase heterogeneity along with the local cortical processing in
the ITC.
PMID- 29329377
TI - Endometrial stem cell-derived granulocyte-colony stimulating factor attenuates
endometrial fibrosis via sonic hedgehog transcriptional activator Gli2.
AB - Intrauterine adhesion (IUA) is characterized by endometrial fibrosis, which
ultimately leads to menstrual abnormalities, infertility, and recurrent
miscarriages. The Shh/Gli2 pathway plays a critical role in tissue fibrogenesis
and regeneration; Gli2 activation induces profibrogenic effects in various
tissues, such as the liver and kidney. However, the role of Gli2 in endometrial
fibrosis remains unknown. The purpose of this study was to test the hypothesis
that activated Gli2 promotes endometrial fibrosis. Endometrial samples from
moderate and severe IUA patients exhibited significantly enhanced expression of
Gli2 compared with normal endometrial samples and mild IUA samples. Transfection
with overactive Gli2 plasmids induced higher fibrosis-related protein expression,
while blocking Gli2 signaling with cyclopamine caused the opposite effect in
endometriotic stromal cells (ESCs), including inducing cell-cycle arrest.
Menstrual-derived stem cell conditioned medium (MenSCs-CM) reduced endometrial
fibrosis by reducing Gli2 protein levels and causing cell-cycle arrest in ESCs
through granulocyte-colony stimulating factor (G-CSF). The effect was weakened
after neutralization with a G-CSF antibody. Gli2 overexpression reduced the
effects of MenSC-CM and G-CSF on fibrosis and cell-cycle progression in vitro.
The antifibrotic effect of G-CSF was also observed in murine model. These
findings demonstrate that Gli2 signaling promotes endometrial fibrosis, and the
inhibition of Gli2 through MenSCs-secreted G-CSF may be of therapeutic value for
managing endometrial fibrosis.
PMID- 29329376
TI - Soil microbial species loss affects plant biomass and survival of an introduced
bacterial strain, but not inducible plant defences.
AB - Background and Aims: Plant growth-promoting rhizobacteria (PGPR) strains can
influence plant-insect interactions. However, little is known about the effect of
changes in the soil bacterial community in general and especially the loss of
rare soil microbes on these interactions. Here, the influence of rare soil
microbe reduction on induced systemic resistance (ISR) in a wild ecotype of
Arabidopsis thaliana against the aphid Myzus persicae was investigated. Methods:
To create a gradient of microbial abundances, soil was inoculated with a serial
dilution of a microbial community and responses of Arabidopsis plants that
originated from the same site as the soil microbes were tested. Plant biomass,
transcription of genes involved in plant defences, and insect performance were
measured. In addition, the effects of the PGPR strain Pseudomonas fluorescens
SS101 on plant and insect performance were tested under the influence of the
various soil dilution treatments. Key Results: Plant biomass showed a hump-shaped
relationship with soil microbial community dilution, independent of aphid or
Pseudomonas treatments. Both aphid infestation and inoculation with Pseudomonas
reduced plant biomass, and led to downregulation of PR1 (salicylic acid
responsive gene) and CYP79B3 (involved in synthesis of glucosinolates). Aphid
performance and gene transcription were unaffected by soil dilution. Conclusions:
Neither the loss of rare microbial species, as caused by soil dilution, nor
Pseudomonas affect the resistance of A. thaliana against M. persicae. However,
both Pseudomonas survival and plant biomass respond to rare species loss. Thus,
loss of rare soil microbial species can have a significant impact on both above-
and below-ground organisms.
PMID- 29329378
TI - Historical crossroads in the conceptual delineation of apathy in Parkinson's
disease.
PMID- 29329379
TI - Asymptomatic Bacteriuria.
PMID- 29329381
TI - The winding path towards rationale anti-thrombotic therapy to prevent stroke in
patients with atrial fibrillation.
PMID- 29329380
TI - Circulating microRNAs as potential biomarkers of disease activity and structural
damage in ankylosing spondylitis patients.
AB - Ankylosing spondylitis (AS) remains difficult to diagnose before irreversible
damage to sacroiliac joint is noticeable. Circulating microRNAs have demonstrated
to serve as diagnostic tools for several human diseases. Here, we analysed plasma
microRNAs to identify potential AS biomarkers. Higher expression levels of
microRNA (miR)-146a-5p, miR-125a-5p, miR-151a-3p and miR-22-3p, and lower
expression of miR-150-5p, and miR-451a were found in AS versus healthy donors.
Interestingly, higher miR-146a-5p, miR-125a-5p, miR-151a-3p, miR-22-3p and miR
451a expression was also observed in AS than psoriatic arthritis patients. The
areas under the curve, generated to assess the accuracy of microRNAs as
diagnostic biomarkers for AS, ranged from 0.614 to 0.781; the six-microRNA
signature reached 0.957. Bioinformatics analysis revealed that microRNAs targeted
inflammatory and bone remodeling genes, underlying their potential role in this
pathology. Indeed, additional studies revealed an association between these six
microRNAs and potential target proteins related to AS pathophysiology.
Furthermore, miR-146a-5p, miR-125a-5p and miR-22-3p expression was increased in
active versus non-active patients. Moreover, miR-125a-5p, miR-151a-3p, miR-150-5p
and miR-451a expression was related to the presence of syndesmophytes in AS
patients. Overall, this study identified a six-plasma microRNA signature that
could be attractive candidates as non-invasive biomarkers for the AS diagnosis,
and may help to elucidate the disease pathogenesis.
PMID- 29329383
TI - Reply to Johnson.
PMID- 29329382
TI - Adolescent Synthetic Cannabinoid Exposure Produces Enduring Changes in Dopamine
Neuron Activity in a Rodent Model of Schizophrenia Susceptibility.
AB - Background: Epidemiological studies recognize cannabis intake as a risk factor
for schizophrenia, yet the majority of adolescents who use marijuana do not
develop psychosis. Similarly, the abuse of synthetic cannabinoids poses a risk
for psychosis. For these reasons, it is imperative to understand the effects of
adolescent cannabinoid exposure in susceptible individuals. Methods: We recently
developed a novel rodent model of schizophrenia susceptibility, the F2
methylazoxymethanol acetate rat, where only a proportion (~40%) of rats display a
schizophrenia-like phenotype. Using this model, we examined the effects of
adolescent synthetic cannabinoid exposure (0.2 mg/kg WIN55, 212-2, i.p.) or
adolescent endocannabinoid upregulation (0.3 mg/kg URB597, i.p.) on dopamine
neuron activity and amphetamine sensitivity in adulthood. Results: Adolescent
synthetic cannabinoid exposure significantly increased the proportion of
susceptible rats displaying a schizophrenia-like hyperdopaminergic phenotype
after puberty without producing any observable alterations in control rats.
Furthermore, this acquired phenotype appears to correspond with alterations in
parvalbumin interneuron function within the hippocampus. Endocannabinoid
upregulation during adolescence also increased the proportion of susceptible rats
developing an increase in dopamine neuron activity; however, it did not alter the
behavioral response to amphetamine, further emphasizing differences between
exogenous and endogenous cannabinoids. Conclusions: Taken together, these studies
provide experimental evidence that adolescent synthetic cannabinoid exposure may
contribute to psychosis in susceptible individuals.
PMID- 29329384
TI - Plaque erosion: a new in vivo diagnosis and a potential major shift in the
management of patients with acute coronary syndromes.
AB - Pathology and in vivo imaging studies have identified superficial plaque erosion
as a frequent and important mechanism underlying acute coronary syndromes (ACS).
In contrast with plaque rupture, the pathophysiological mechanisms leading to
plaque erosion remain poorly understood. The advent of intravascular imaging
techniques, particularly optical coherence tomography, has aided understanding of
this mode of ACS in vivo by complementing previous insights from pathology
studies. Appreciation of the distinct biological and clinical mechanisms of
plaque erosion points to the possibility of tailored management strategies for
patients presenting with ACS.
PMID- 29329385
TI - Reassessing the Evidence for Capacity Limits in Neural Signals Related to Working
Memory.
AB - In 2004, two landmark studies described the discovery of brain imaging
(functional magnetic resonance imaging and electroencephalography) signals that
increase with the number of items held in visual working memory (WM). These
studies claimed that the signals leveled off (plateaued) once the number of
memoranda reached the capacity of WM, as estimated by the prevailing model of the
time. However, alternative models were not considered, and changing concepts of
WM in the more than a decade since these studies were published necessitate a re
evaluation of their findings; newer models that provide the most accurate account
of behavioral data do not incorporate a fixed limit on the number of items
stored. Furthermore, an important claim made about the original studies, that
signals plateau at each individual's estimated capacity, has never been tested.
Here, we pit the plateau model of signal strength against an alternative,
saturation model, a biophysically plausible account in which signals increase
continuously without plateau. We show that the saturation model provides a better
description of the original data, challenging the assumption that imaging results
provide evidence for a fixed item limit in WM.
PMID- 29329386
TI - The role of service readiness and health care facility factors in attrition from
Option B+ in Haiti: a joint examination of electronic medical records and service
provision assessment survey data.
AB - Background: Option B+ is a strategy wherein pregnant or breastfeeding women with
HIV are enrolled in lifelong antiretroviral therapy (ART) for prevention of
mother-to-child transmission (PMTCT) of HIV. In Haiti, attrition from Option B+
is problematic and variable across health care facilities. This study explores
service readiness and other facility factors as predictors of Option B+ attrition
in Haiti. Methods: This analysis used longitudinal data from 2012 to 2014 from
the iSante electronic medical record system and cross-sectional data from Haiti's
2013 Service Provision Assessment. Predictors included Service Availability and
Readiness Assessment (SARA) measures for antenatal care (ANC), PMTCT, HIV care
services and ART services; general facility characteristics and patient-level
factors. Multivariable Cox proportional hazards models modelled the time to first
attrition. Results: Analysis of data from 3147 women at 63 health care facilities
showed no significant relationships between SARA measures and attrition. Having
integrated ANC/PMTCT care and HIV-related training were significant protective
factors. Being a public-sector facility, having a greater number of quality
improvement activities and training in ANC were significant risk factors.
Conclusion: Several facility-level factors were associated with Option B+
attrition. Future research is needed to explore unmeasured facility factors,
clarify causal relationships, and incorporate community-level factors into the
analysis of Option B+ attrition.
PMID- 29329387
TI - Patients with acephalic spermatozoa syndrome linked to SUN5 mutations have a
favorable pregnancy outcome from ICSI.
AB - STUDY QUESTION: Are Sad1 and UNC84 domain containing 5 (SUN5) mutations
associated with the outcomes of ICSI in patients with acephalic spermatozoa
syndrome (ASS)? SUMMARY ANSWER: Despite highly abnormal sperm morphology, ASS
patients with SUN5 mutations have a favorable pregnancy outcome following ICSI.
WHAT IS KNOWN ALREADY: ASS is a rare cause of infertility characterized by the
production of a majority of headless spermatozoa, along with a small proportion
of intact spermatozoa with an abnormal head-tail junction. Previous studies have
demonstrated that SUN5 mutations may cause ASS. Several studies showed that ICSI
could help patients with ASS father children. STUDY DESIGN, SIZE, DURATION: This
retrospective cohort study included 11 infertile ASS males with SUN5 mutations.
Five of them underwent five ICSI cycles. Their ICSI results were compared to men
with ASS without SUN5 mutations (n = 3) and to men with multiple morphological
abnormalities of the sperm flagella (MMAF) (n = 9). All ICSI treatments were
completed between Jan 2011 and May 2017. PARTICIPANTS/MATERIALS, SETTING,
METHODS: Sanger DNA sequencing was used to detect mutations in SUN5. Clinical and
biological data were collected from patients at the fertility center. MAIN
RESULTS AND THE ROLE OF CHANCE: Sanger sequencing validated 11 patients with SUN5
mutations. Three novel mutations in SUN5 (c.829C>T [p.Q277*]; c.1067G>A
[p.R356H]; c.211+1 insGT [p.S71Cfs11*]) were identified in three patients. The
rates of fertilization, good-quality embryos and pregnancy for five patients with
SUN5 mutations following ICSI were 81.5%, 81.8% and 100%, respectively. The rates
of fertilization and good-quality embryos in patients with MMAF were
significantly lower compared with ASS patients (65.6 versus 82.4%, P = 0.039 and
53.6 versus 85.2%, P = 0.031, respectively). There were no differences in ICSI
results between ASS patients with and without SUN5 mutations. LIMITATIONS,
REASONS FOR CAUTION: Only a small number patients with SUN5 mutations was
available because of its rare incidence. WIDER IMPLICATIONS OF THE FINDINGS:
Patients with ASS can be effectively treated with ICSI. SUN5 mutations may be one
of the genetic causes of ASS. STUDY FUNDING/COMPETING INTEREST(S): This study was
supported by the National Natural Science Foundation of China (81401251,
81370754, and 81170559), the Jiangsu Province Special Program of Medical Science
(BL2012009, ZX201110, FXK201221) and a project funded by PAPD of the Priority
Academic Program Development of Jiangsu High Education Institutions (JX10231802).
None of the authors have any competing interests.
PMID- 29329388
TI - A Series of Deaths Involving Carfentanil in the UK and Associated Post-mortem
Blood Concentrations.
AB - The potent opioid and veterinary drug, carfentanil has recently entered the
illicit drug market, especially in relation to heroin and cocaine. Recent
publications have reported carfentanil concentrations found in fatalities
occurring in the USA. This article presents the toxicological findings in seven
heroin/cocaine cases occurring in the UK within a short period of time where
carfentanil was detected and measured. Carfentanil was detected along with other
drugs in all cases with no alcohol detected in the post-mortem blood in any of
the cases. Of the other drugs detected, of particular note, cannabinoids were
detected in three, cocaine in four, other opioids (methadone, dihydrocodeine and
tramadol) in four and benzodiazepines were detected in four of the seven
fatalities. A high concentration of ketamine and norketamine was found in one
case. Morphine and its glucuronide metabolites were also measured where detected
in six of the seven cases. The carfentanil concentrations were found to be
between 0.22 and 3.3 ng/mL (mean 0.93, median 0.66 ng/mL) in post-mortem femoral
blood. In one case where aortic and ventricular post-mortem blood was submitted
for analysis in addition to femoral blood, comparative concentrations of 1.05
(aortic), 0.57 (ventricular) and 0.50 (femoral) ng/mL were found. The
concentrations support the necessity to ensure laboratory detection methods for
carfentanil and subsequent measurement are appropriate as concentrations below
0.3 ng/mL may be present in post-mortem blood. The concentrations also support
the notion that there is no particular "toxic" or "fatal" post-mortem blood
carfentanil concentration associated with its use.
PMID- 29329389
TI - In vivo daptomycin efficacy against experimental vancomycin-resistant
Enterococcus faecium endocarditis.
AB - Objectives: Daptomycin has become a first-line therapeutic option for vancomycin
resistant Enterococcus faecium infective endocarditis (IE). Although high doses
(>=8 mg/kg) are often recommended, optimal doses, particularly for strains with
MICs close to the susceptibility breakpoint (4 mg/L), are still debated. Methods:
Daptomycin efficacy at doses equivalent to 8 mg/kg daptomycin (DAP8) and 12 mg/kg
daptomycin (DAP12) in humans was evaluated in a rabbit model of aortic valve IE
induced by 108 cfu of E. faecium reference strain Aus0004 (daptomycin MIC = 2
mg/L) or its in vitro mutant strain Mut4 (daptomycin MIC = 4 mg/L). Treatment
began 48 h post-inoculation and lasted 5 days. Results: With Aus0004, the median
log10 cfu/g of vegetations was significantly lower after DAP8 and DAP12 versus
controls [6.05 (n = 12) and 2.15 (n = 10) versus 9.14 (n = 11), respectively; P <
0.001], with DAP12 being more effective than DAP8 concerning vegetation bacterial
load (P < 0.001) and percentages of sterile vegetations (100% versus 0%,
respectively; P < 0.001). Daptomycin-resistant Aus0004 mutants were detected in
8.3% of DAP8-treated vegetations. With Mut4, the median log10 cfu/g of
vegetations was significantly lower after DAP8 and DAP12 versus controls [7.7 (n
= 11) and 6.95 (n = 10) versus 9.59 (n = 11), respectively; P = 0.001 and P =
0.002], without any between-dose difference, but no vegetation was sterile.
Moreover, 7 of 11 (63.6%) and 7 of 9 (77.8%) vegetations contained resistant
mutants after DAP8 and DAP12, respectively. Conclusions: DAP12 was the most
successful strategy against IE due to a WT E. faecium strain (daptomycin MIC = 2
mg/L). To treat IE strains with MIC = 4 mg/L, DAP8 or DAP12 monotherapy was
poorly effective with the risk of resistant mutant emergence. Reassessment of the
daptomycin susceptibility breakpoint for enterococci seems necessary.
PMID- 29329390
TI - Human oocyte calcium analysis predicts the response to assisted oocyte activation
in patients experiencing fertilization failure after ICSI.
AB - STUDY QUESTION: Can human oocyte calcium analysis predict fertilization success
after assisted oocyte activation (AOA) in patients experiencing fertilization
failure after ICSI? SUMMARY ANSWER: ICSI-AOA restores the fertilization rate only
in patients displaying abnormal Ca2+ oscillations during human oocyte activation.
WHAT IS KNOWN ALREADY: Patients capable of activating mouse oocytes and who
showed abnormal Ca2+ profiles after mouse oocyte Ca2+ analysis (M-OCA), have
variable responses to ICSI-AOA. It remains unsettled whether human oocyte Ca2+
analysis (H-OCA) would yield an improved accuracy to predict fertilization
success after ICSI-AOA. STUDY DESIGN, SIZE, DURATION: Sperm activation potential
was first evaluated by MOAT. Subsequently, Ca2+ oscillatory patterns were
determined with sperm from patients showing moderate to normal activation
potential based on the capacity of human sperm to generate Ca2+ responses upon
microinjection in mouse and human oocytes. Altogether, this study includes a
total of 255 mouse and 122 human oocytes. M-OCA was performed with 16 different
sperm samples before undergoing ICSI-AOA treatment. H-OCA was performed for 11
patients who finally underwent ICSI-AOA treatment. The diagnostic accuracy to
predict fertilization success was calculated based on the response to ICSI-AOA.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients experiencing low or total
failed fertilization after conventional ICSI were included in the study. All
participants showed moderate to high rates of activation after MOAT. Metaphase II
(MII) oocytes from B6D2F1 mice were used for M-OCA. Control fertile sperm samples
were used to obtain a reference Ca2+ oscillation profile elicited in human
oocytes. Donated human oocytes, non-suitable for IVF treatments, were collected
and vitrified at MII stage for further analysis by H-OCA. MAIN RESULTS AND THE
ROLE OF CHANCE: M-OCA and H-OCA predicted the response to ICSI-AOA in 8 out of 11
(73%) patients. Compared to M-OCA, H-OCA detected the presence of sperm
activation deficiencies with greater sensitivity (75 vs 100%, respectively). ICSI
AOA never showed benefit to overcome fertilization failure in patients showing
normal capacity to generate Ca2+ oscillations in H-OCA and was likely to be
beneficial in cases displaying abnormal H-OCA Ca2+ oscillations patterns.
LIMITATIONS, REASONS FOR CAUTION: The scarce availability of human oocytes
donated for research purposes is a limiting factor to perform H-OCA. Ca2+ imaging
requires specific equipment to monitor fluorescence changes over time. WIDER
IMPLICATIONS OF THE FINDINGS: H-OCA is a sensitive test to diagnose gamete-linked
fertilization failure. H-OCA allows treatment counseling for couples experiencing
ICSI failures to either undergo ICSI-AOA or to participate in gamete donation
programs. The present data provide an important template of the Ca2+ signature
observed during human fertilization in cases with normal, low and failed
fertilization after conventional ICSI. STUDY FUNDING/COMPETING INTEREST(S): This
work was supported by the Flemish fund for scientific research (FWO-Vlaanderen,
G060615N). The authors have no conflict of interest to declare.
PMID- 29329391
TI - Oxidative burst and Dectin-1-triggered phagocytosis affected by norepinephrine
and endocannabinoids: implications for fungal clearance under stress.
AB - A prolonged stress burden is known to hamper the efficiency of both the innate
and the adaptive immune systems and to attenuate the stress responses by the
catecholaminergic and endocannabinoid (EC) systems. Key mechanisms of innate
immunity are the eradication of pathogens through phagocytosis and the
respiratory burst. We tested the concentration-dependent, spontaneous and
stimulated (via TNFalpha and N-formylmethionine-leucyl-phenylalanine) release of
reactive oxygen species (ROS) by human polymorphonuclear leukocytes (PMNs) in
vitro in response to norepinephrine (NE) and AM1241, a pharmacological ligand for
the EC receptor CB2. We evaluated phagocytosis of Dectin-1 ligating zymosan
particles and tested the cytokine response against Candida antigen in an in vitro
cytokine release assay. Increasing concentrations of NE did not affect
phagocytosis, yet stimulated ROS release was attenuated gradually reaching
maximum suppression at 500 nM. Adrenergic receptor (AR) mechanisms using non-AR
selective (labetalol) as well as specific alpha-(prazosin) and beta-(propranolol)
receptor antagonists were tested. Results show that only labetalol and
propranolol were able to recuperate cytotoxicity in the presence of NE,
evidencing a beta-receptor-mediated effect. The CB2 agonist, AM1241, inhibited
phagocytosis at 10 uM and spontaneous peroxide release by PMNs. Use of the
inverse CB2 receptor agonist SR144528 led to partial recuperation of ROS
production, confirming the functional role of CB2. Additionally, AM1241 delayed
early activation of monocytes and induced suppression of IL-2 and IL-6 levels in
response to Candida via lower activity of mammalian target of rapamycin (mTOR).
These findings provide new insights into key mechanisms of innate immunity under
stressful conditions where ligands to the sympatho-adrenergic and EC system are
released.
PMID- 29329393
TI - TGF-beta-mediated NADPH oxidase 4-dependent oxidative stress promotes colistin
induced acute kidney injury.
AB - Background: Colistin (polymyxin E) is an important constituent of the polymyxin
class of cationic polypeptide antibiotics. Intrarenal oxidative stress can
contribute to colistin-induced nephrotoxicity. Nicotinamide adenine dinucleotide
3-phosphate oxidases (Noxs) are important sources of reactive oxygen species.
Among the various types of Noxs, Nox4 is predominantly expressed in the kidney.
Objectives: We investigated the role of Nox4 and benefit of Nox4 inhibition in
colistin-induced acute kidney injury using in vivo and in vitro models. Methods:
Human proximal tubular epithelial (HK-2) cells were treated with colistin with or
without NOX4 knockdown, or GKT137831 (most specific Nox1/4 inhibitor). Effects of
Nox4 inhibition on colistin-induced acute kidney injury model in Sprague-Dawley
rats were examined. Results: Nox4 expression in HK-2 cells significantly
increased following colistin exposure. SB4315432 (transforming growth factor
beta1 receptor I inhibitor) significantly inhibited Nox4 expression in HK-2
cells. Knockdown of NOX4 transcription reduced reactive oxygen species
production, lowered the levels of pro-inflammatory markers (notably mitogen
activated protein kinases) implicated in colistin-induced nephrotoxicity and
attenuated apoptosis by altering Bax and caspase 3/7 activity. Pretreatment with
GKT137831 replicated these effects mediated by downregulation of mitogen
activated protein kinase activities. In a rat colistin-induced acute kidney
injury model, administration of GKT137831 resulted in attenuated colistin-induced
acute kidney injury as indicated by attenuated impairment of glomerulus function,
preserved renal structures, reduced expression of 8-hydroxyguanosine and fewer
apoptotic cells. Conclusions: Collectively, these findings identify Nox4 as a key
source of reactive oxygen species responsible for kidney injury in colistin
induced nephrotoxicity and highlight a novel potential way to treat drug-related
nephrotoxicity.
PMID- 29329392
TI - Risk of pancreatic cancer associated with family history of cancer and other
medical conditions by accounting for smoking among relatives.
AB - Background: Family history (FH) of pancreatic cancer (PC) has been associated
with an increased risk of PC, but little is known regarding the role of
inherited/environmental factors or that of FH of other comorbidities in PC risk.
We aimed to address these issues using multiple methodological approaches.
Methods: Case-control study including 1431 PC cases and 1090 controls and a
reconstructed-cohort study (N = 16 747) made up of their first-degree relatives
(FDR). Logistic regression was used to evaluate PC risk associated with FH of
cancer, diabetes, allergies, asthma, cystic fibrosis and chronic pancreatitis by
relative type and number of affected relatives, by smoking status and other
potential effect modifiers, and by tumour stage and location. Familial
aggregation of cancer was assessed within the cohort using Cox proportional
hazard regression. Results: FH of PC was associated with an increased PC risk
[odds ratio (OR) = 2.68; 95% confidence interval (CI): 2.27-4.06] when compared
with cancer-free FH, the risk being greater when >= 2 FDRs suffered PC (OR =
3.88; 95% CI: 2.96-9.73) and among current smokers (OR = 3.16; 95% CI: 2.56-5.78,
interaction FHPC*smoking P-value = 0.04). PC cumulative risk by age 75 was 2.2%
among FDRs of cases and 0.7% in those of controls [hazard ratio (HR) = 2.42; 95%
CI: 2.16-2.71]. PC risk was significantly associated with FH of cancer (OR =
1.30; 95% CI: 1.13-1.54) and diabetes (OR = 1.24; 95% CI: 1.01-1.52), but not
with FH of other diseases. Conclusions: The concordant findings using both
approaches strengthen the notion that FH of cancer, PC or diabetes confers a
higher PC risk. Smoking notably increases PC risk associated with FH of PC.
Further evaluation of these associations should be undertaken to guide PC
prevention strategies.
PMID- 29329395
TI - Open-Access Physical Activity Programs for Older Adults: A Pragmatic and
Systematic Review.
AB - Background and Objectives: Open-access, community-based programs are recommended
to assist older adults in meeting physical activity guidelines, but the
characteristics, impact, and scalability of these programs is less understood.
The Land-Grant University Cooperative Extension System, an organization providing
education through county-based educators, functions as a delivery system for
these programs. A systematic review was conducted to determine characteristics of
effective older adult physical activity programs and the extent to which programs
delivered in Extension employ these characteristics. Research Design and Methods:
A systematic review of peer-reviewed and grey literature was conducted from
August 2016 to February 2017. The review was limited to open-access (available to
all), community-based physical activity interventions for older adults (>=65
years of age). The peer-reviewed literature search was conducted in PubMed and
EBSCOhost; the grey literature search for Extension interventions was conducted
through Extension websites, Land-Grant Impacts, and the Journal of Extension.
Results: Sixteen peer-reviewed studies and 17 grey literature sources met
inclusion criteria and were analyzed. Peer-reviewed and Extension programs were
similar in their limited use of behavioral theories and group-based strategies.
Compared to Extension programs, those in the peer-reviewed literature were more
likely to use a combination of physical activity components and be delivered by
trained professionals. Discussion and Implications: The results indicate notable
differences between peer-reviewed literature and Extension programs and present
an opportunity for Extension programs to more effectively use evidence-based
program characteristics, including behavioral theories and group dynamics, a
combination of physical activity components, and educator/agent-trained delivery
agents.
PMID- 29329394
TI - Analysis of the Aedes albopictus C6/36 genome provides insight into cell line
utility for viral propagation.
AB - Background: The 50-year-old Aedes albopictus C6/36 cell line is a resource for
the detection, amplification, and analysis of mosquito-borne viruses including
Zika, dengue, and chikungunya. The cell line is derived from an unknown number of
larvae from an unspecified strain of Aedes albopictus mosquitoes. Toward improved
utility of the cell line for research in virus transmission, we present an
annotated assembly of the C6/36 genome. Results: The C6/36 genome assembly has
the largest contig N50 (3.3 Mbp) of any mosquito assembly, presents the sequences
of both haplotypes for most of the diploid genome, reveals independent null
mutations in both alleles of the Dicer locus, and indicates a male-specific
genome. Gene annotation was computed with publicly available mosquito transcript
sequences. Gene expression data from cell line RNA sequence identified enrichment
of growth-related pathways and conspicuous deficiency in aquaporins and inward
rectifier K+ channels. As a test of utility, RNA sequence data from Zika-infected
cells were mapped to the C6/36 genome and transcriptome assemblies. Host
subtraction reduced the data set by 89%, enabling faster characterization of
nonhost reads. Conclusions: The C6/36 genome sequence and annotation should
enable additional uses of the cell line to study arbovirus vector interactions
and interventions aimed at restricting the spread of human disease.
PMID- 29329396
TI - Patient-level benefits associated with decentralization of antiretroviral therapy
services to primary health facilities in Malawi and Uganda.
AB - Background: The Lablite project captured information on access to antiretroviral
therapy (ART) at larger health facilities ('hubs') and lower-level health
facilities ('spokes') in Phalombe district, Malawi and in Kalungu district,
Uganda. Methods: We conducted a cross-sectional survey among patients who had
transferred to a spoke after treatment initiation (Malawi, n=54; Uganda, n=33),
patients who initiated treatment at a spoke (Malawi, n=50; Uganda, n=44) and
patients receiving treatment at a hub (Malawi, n=44; Uganda, n=46). Results: In
Malawi, 47% of patients mapped to the two lowest wealth quintiles (Q1-Q2);
patients at spokes were poorer than at a hub (57% vs 23% in Q1-Q2; p<0.001). In
Uganda, 7% of patients mapped to Q1-Q2; patients at the rural spoke were poorer
than at the two peri-urban facilities (15% vs 4% in Q1-Q2; p<0.001). The median
travel time one way to a current ART facility was 60 min (IQR 30-120) in Malawi
and 30 min (IQR 20-60) in Uganda. Patients who had transferred to the spokes
reported a median reduction in travel time of 90 min in Malawi and 30 min in
Uganda, with reductions in distance and food costs. Conclusions: Decentralizing
ART improves access to treatment. Community-level access to treatment should be
considered to further minimize costs and time.
PMID- 29329397
TI - MINAR1 is a Notch2-binding protein that inhibits angiogenesis and breast cancer
growth.
AB - Intrinsically disordered proteins (IDPs)/intrinsically unstructured proteins are
characterized by the lack of fixed or stable tertiary structure, and are
increasingly recognized as an important class of proteins with major roles in
signal transduction and transcriptional regulation. In this study, we report the
identification and functional characterization of a previously uncharacterized
protein (UPF0258/KIAA1024), major intrinsically disordered Notch2-associated
receptor 1 (MINAR1). While MINAR1 carries a single transmembrane domain and a
short cytoplasmic domain, it has a large extracellular domain that shares no
similarity with known protein sequences. Uncharacteristically, MINAR1 is a highly
IDP with nearly 70% of its amino acids sequences unstructured. We demonstrate
that MINAR1 physically interacts with Notch2 and its binding to Notch2 increases
its stability and function. MINAR1 is widely expressed in various tissues
including the epithelial cells of the breast and endothelial cells of blood
vessels. MINAR1 plays a negative role in angiogenesis as it inhibits angiogenesis
in cell culture and in mouse matrigel plug and zebrafish angiogenesis models.
Furthermore, while MINAR1 is highly expressed in the normal human breast, its
expression is significantly downregulated in advanced human breast cancer and its
re-expression in breast cancer cells inhibited tumor growth. Our study
demonstrates that MINAR1 is an IDP that negatively regulates angiogenesis and
growth of breast cancer cells.
PMID- 29329398
TI - LeNup: learning nucleosome positioning from DNA sequences with improved
convolutional neural networks.
AB - Motivation: Nucleosome positioning plays significant roles in proper genome
packing and its accessibility to execute transcription regulation. Despite a
multitude of nucleosome positioning resources available on line including
experimental datasets of genome-wide nucleosome occupancy profiles and
computational tools to the analysis on these data, the complex language of
eukaryotic Nucleosome positioning remains incompletely understood. Results: Here,
we address this challenge using an approach based on a state-of-the-art machine
learning method. We present a novel convolutional neural network (CNN) to
understand nucleosome positioning. We combined Inception-like networks with a
gating mechanism for the response of multiple patterns and long term association
in DNA sequences. We developed the open-source package LeNup based on the CNN to
predict nucleosome positioning in Homo sapiens, Caenorhabditis elegans,
Drosophila melanogaster as well as Saccharomyces cerevisiae genomes. We trained
LeNup on four benchmark datasets. LeNup achieved greater predictive accuracy than
previously published methods. Availability and implementation: LeNup is freely
available as Python and Lua script source code under a BSD style license from
https://github.com/biomedBit/LeNup. Contact: jhzhang@bit.edu.cn. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 29329399
TI - Yield Losses in Transgenic Cry1Ab and Non-Bt Corn as Assessed Using a Crop-Life
Table Approach.
AB - In this study, we constructed crop life tables for Bacillus thuringiensis
Berliner (Bt) Cry1Ab and non-Bt corn hybrids, in which yield-loss factors and
abundance of predaceous arthropods were recorded during 2 yr at two locations.
Corn kernel/grain was the yield component that had the heaviest losses and that
determined the overall yield loss in the corn hybrids across years and locations.
Yield losses in both corn hybrids were primarily caused by kernel-destroying
insects. Helicoverpa zea (Boddie) and Spodoptera frugiperda (Smith) (Lepidoptera:
Noctuidae) were the key loss factors at one location, while at the other, the key
loss factor was the silk fly larvae, Euxesta spp. (Diptera: Ulidiidae). Although
the realized yield of corn grains was not different (P > 0.05) between Cry1Ab and
non-Bt corn hybrids, the Bt corn hybrid reduced (P < 0.05) the damage by H. zea
and S. frugiperda in three of the four field trials, particularly at the location
where Lepidoptera were the key loss factors. As expected, no reduction in the
abundance of predaceous arthropods was observed in Cry1Ab corn fields. Various
species of natural enemies were recorded, particularly the earwig Doru luteipes
(Scudder) (Dermaptera: Forficulidae), which was the most abundant and frequent
predaceous insect. These results indicate that integration of pest management
practices should be pursued to effectively minimize losses by kernel-destroying
insects during corn reproductive stages when growing non-Bt or certain low-dose
Bt corn cultivars for fall armyworm and corn earworm, such as those producing
Cry1Ab or other Cry toxins.
PMID- 29329400
TI - The decision to work after state pension age and how it affects quality of life:
evidence from a 6-year English panel study.
AB - Background: despite an increasing proportion of older people working beyond State
Pension Age (SPA), little is known about neither the motivations for this
decision nor whether, and to what extent, working beyond SPA affects quality of
life (QoL). Methods: QoL was measured using the CASP-19 scale. Respondents in
paid work beyond SPA were distinguished based on whether they reported financial
constraints as the main reason for continuing in work. Linear regression models
were used to assess the associations between paid work beyond SPA and CASP-19
scores among men aged 65-74 and women aged 60-69 (n = 2,502) cross-sectionally
and over time using Wave 4 and Wave 7 of the English Longitudinal Study of
Ageing. Results: approximately, one in five respondents were in paid work beyond
SPA, one-third of whom reported financial issues as the main reason. These
individuals reported significantly lower CASP-19 scores (beta = -1.21) compared
with those who retired at the expected/usual age. Respondents who declared being
in paid work beyond SPA because they enjoyed their work or wanted to remain
active, reported significantly higher QoL (beta = 1.62). Longitudinal analyses
suggest that those who were working post-SPA by choice, but who had stopped
working at follow-up, also reported marginally (P < 0.10) higher CASP-19 scores.
Conclusions: potential QoL benefits of working beyond SPA need to be considered
in light of individual motivations for extending working life. Given the trend
towards working longer and the abolishment of mandatory retirement ages, it is
important that older people maintain control over their decision to work in later
life.
PMID- 29329402
TI - Discovering foodborne illness in online restaurant reviews.
AB - Objective: We developed a system for the discovery of foodborne illness mentioned
in online Yelp restaurant reviews using text classification. The system is used
by the New York City Department of Health and Mental Hygiene (DOHMH) to monitor
Yelp for foodborne illness complaints. Materials and Methods: We built
classifiers for 2 tasks: (1) determining if a review indicated a person
experiencing foodborne illness and (2) determining if a review indicated multiple
people experiencing foodborne illness. We first developed a prototype classifier
in 2012 for both tasks using a small labeled dataset. Over years of system
deployment, DOHMH epidemiologists labeled 13 526 reviews selected by this
classifier. We used these biased data and a sample of complementary reviews in a
principled bias-adjusted training scheme to develop significantly improved
classifiers. Finally, we performed an error analysis of the best resulting
classifiers. Results: We found that logistic regression trained with bias
adjusted augmented data performed best for both classification tasks, with F1
scores of 87% and 66% for tasks 1 and 2, respectively. Discussion: Our error
analysis revealed that the inability of our models to account for long phrases
caused the most errors. Our bias-adjusted training scheme illustrates how to
improve a classification system iteratively by exploiting available biased
labeled data. Conclusions: Our system has been instrumental in the identification
of 10 outbreaks and 8523 complaints of foodborne illness associated with New York
City restaurants since July 2012. Our evaluation has identified strong
classifiers for both tasks, whose deployment will allow DOHMH epidemiologists to
more effectively monitor Yelp for foodborne illness investigations.
PMID- 29329403
TI - Host-Tree Selection by the Invasive Argentine Ant (Hymenoptera: Formicidae) in
Relation to Honeydew-Producing Insects.
AB - The Argentine ant, Linepithema humile (Mayr; Hymenoptera: Formicidae), is one of
the world's most hazardous invasive species, and thus its eradication from Japan
is important. Physical and chemical controls can be expensive and cause strong
adverse effects on local terrestrial ecosystems regardless of their high
efficacy. Here, presence/absence of host-tree selection by Argentine ants was
investigated to understand the ant-honeydew-producing insects interactions in
order to develop new cultural controls compatible with biodiversity conservation.
Abundance of Argentine ants and their tree utilization ratio was measured among
dominant roadside trees (Cinnamomum camphora, Myrica rubra, Nerium indicum,
Rhaphiolepis indica var. umbellata, Juniperus chinensis var. kaizuka) in two
areas around Kobe, Japan. Almost all ants collected were Argentine ants
suggesting that native ants would have been competitively excluded. Tree
utilization of Argentine ants clearly differed among host trees. Abundance of
both Argentine ants and honeydew-producing insects and tree utilization rate of
the ants were significantly lower in especially C. camphora and J. chinensis. Few
Argentine ants were observed trailing on C. camphora, J. Chinensis, and N.
indicum, most probably due to low abundance of honeydew-producing insects on
these trees with the toxic and repellent chemical components. On the other hand,
high abundance of both Argentine ants and homopterans were found in M. rubra and
especially R. indica. We suggest that reductions of R. indica and M. rubra would
lead to a decrease in abundance of honeydew-producing insects, and thus
effectively control populations of Argentine ants. At the same time, planting of
C. camphora, J. Chinensis, and N. indicum may also play a role in restraint
efficacy against invasion of the invasive ants.
PMID- 29329404
TI - Response.
PMID- 29329401
TI - Morphological and Functional Characterization of Non-fast-Spiking GABAergic
Interneurons in Layer 4 Microcircuitry of Rat Barrel Cortex.
AB - GABAergic interneurons are notorious for their heterogeneity, despite
constituting a small fraction of the neuronal population in the neocortex.
Classification of interneurons is crucial for understanding their widespread
cortical functions as they provide a complex and dynamic network, balancing
excitation and inhibition. Here, we investigated different types of non-fast
spiking (nFS) interneurons in Layer 4 (L4) of rat barrel cortex using whole-cell
patch-clamp recordings with biocytin-filling. Based on a quantitative analysis on
a combination of morphological and electrophysiological parameters, we identified
5 distinct types of L4 nFS interneurons: 1) trans-columnar projecting
interneurons, 2) locally projecting non-Martinotti-like interneurons, 3) supra
granular projecting Martinotti-like interneurons, 4) intra-columnar projecting
VIP-like interneurons, and 5) locally projecting neurogliaform-like interneurons.
Trans-columnar projecting interneurons are one of the most striking interneuron
types, which have not been described so far in Layer 4. They feature extensive
axonal collateralization not only in their home barrel but also in adjacent
barrels. Furthermore, we identified that most of the L4 nFS interneurons express
somatostatin, while few are positive for the transcription factor Prox1. The
morphological and electrophysiological characterization of different L4 nFS
interneuron types presented here provides insights into their synaptic
connectivity and functional role in cortical information processing.
PMID- 29329405
TI - Solanaceous exocyst subunits are involved in immunity to diverse plant pathogens.
AB - The exocyst, a multiprotein complex consisting of eight subunits, plays an
essential role in many biological processes by mediating secretion of post-Golgi
derived vesicles towards the plasma membrane. In recent years, roles for plant
exocyst subunits in pathogen defence have been uncovered, largely based on
studies in the model plant Arabidopsis. Only a few studies have been undertaken
to assign the role of exocyst subunits in plant defence in other plants species,
including crops. In this study, predicted protein sequences from exocyst subunits
were retrieved by mining databases from the Solanaceous plants Nicotiana
benthamiana, tomato, and potato. Subsequently, their evolutionary relationship
with Arabidopsis exocyst subunits was analysed. Gene silencing in N. benthamiana
showed that several exocyst subunits are required for proper plant defence
against the (hemi-)biotrophic plant pathogens Phytophthora infestans and
Pseudomonas syringae. In contrast, some exocyst subunits seem to act as
susceptibility factors for the necrotrophic pathogen Botrytis cinerea.
Furthermore, the majority of the exocyst subunits were found to be involved in
callose deposition, suggesting that they play a role in basal plant defence. This
study provides insight into the evolution of exocyst subunits in Solanaceous
plants and is the first to show their role in immunity against multiple unrelated
pathogens.
PMID- 29329406
TI - Judgement of Breath Alcohol Concentration Levels Among Pedestrians in the Night
Time Economy-A Street-Intercept Field Study.
AB - Aims: To evaluate how well people in the night-time economy can assess their own
breath alcohol concentration (BrAC), in the context of a change in breath alcohol
limits for driving. Methods: We conducted a field study of 242 participants over
5 nights in the central business district of a university town in New Zealand.
Participants completed a short survey, which included questions on their self
reported level of intoxication and the self-estimated BrAC. At the conclusion of
the interview each participant was breath-tested. We compared actual and self
estimated BrAC using a scatter plot and multiple regression methods. Results: The
average BrAC error was 61.7 MUg/l, meaning that on average participants
overestimate their BrAC. Participants with a BrAC below 487 MUg/l tended to
overestimate their BrAC on average, and those with a BrAC above 487 MUg/l tended
to underestimate their BrAC on average. Regression results supported this
observation, but also found that men who are not 'out on a typical night'
overestimate their BrAC by more. Conclusions: Drinkers in this naturalistic
setting have little idea of their level of intoxication, as measured by BrAC.
However, this uncertainty may be advantageous to public health outcomes, since if
drinkers are uncertain about their level of intoxication relative to the legal
limit, this may lead them to avoid drunk driving. Short Summary: A field study of
drinkers in the night-time economy of a New Zealand university town was conducted
to evaluate how well drinkers can assess their breath alcohol concentration
(BrAC). Drinkers in this setting inaccurately estimate their intoxication, and
those with higher BrAC tended to underestimate their BrAC on average.
PMID- 29329407
TI - Transplant Buccaneers: P.K. Sen and India's First Heart Transplant, February
1968.
AB - On 17 February 1968, Bombay surgeon Prafulla Kumar Sen transplanted a human
heart, becoming the fourth surgeon in the world to attempt the feat. Even though
the patient survived just three hours, the feat won Sen worldwide acclaim. The
ability of Sen's team to join the ranks of the world's surgical pioneers raises
interesting questions. How was Sen able to transplant so quickly? He had to train
a team of collaborators, import or reverse engineer technologies and techniques
that had been developed largely in the United States, and begin conversations
with Indian political authorities about the contested concept of brain death. The
effort that this required raises questions of why. Sen, who worked at a city
hospital in Bombay that could not provide basic care for all its citizens, sought
a technology that epitomized high-risk high-cost, health care. To accomplish his
feat, Sen navigated Cold War tensions and opportunities, situating his interests
into those of his hospital, municipal authorities, Indian nationalism, Soviet and
American authorities, the Rockefeller Foundation, and others. The many contexts
and interests that made Sen's work possible created opportunities for many
different judgments about the success or failure of medical innovation.
PMID- 29329408
TI - An Orientation Map for Disparity-Defined Edges in Area V4.
AB - Binocular disparity information is an important source of 3D perception. Neurons
sensitive to binocular disparity are found in almost all major visual areas in
nonhuman primates. In area V4, disparity processes are suggested for the purposes
of 3D-shape representation and fine disparity perception. However, whether
neurons in V4 are sensitive to disparity-defined edges used in shape
representation is not clear. Additionally, a functional organization for
disparity edges has not been demonstrated so far. With intrinsic signal optical
imaging, we studied functional organization for disparity edges in the monkey
visual areas V1, V2, and V4. We found that there is an orientation map in V4
activated by edges purely defined by binocular disparity. This map is consistent
with the orientation map obtained with regular luminance-defined edges,
indicating a cue-invariant edge representation in this area. In contrast, such a
map is much weaker in V2 and totally absent in V1. These findings reveal a
hierarchical processing of 3D shape along the ventral pathway and the important
role that V4 plays in shape-from-disparity detection.
PMID- 29329409
TI - Recent development of Ori-Finder system and DoriC database for microbial
replication origins.
AB - DNA replication begins at replication origins in all three domains of life.
Identification and characterization of replication origins are important not only
in providing insights into the structure and function of the replication origins
but also in understanding the regulatory mechanisms of the initiation step in DNA
replication. The Z-curve method has been used in the identification of
replication origins in archaeal genomes successfully since 2002. Furthermore, the
Web servers of Ori-Finder and Ori-Finder 2 have been developed to predict
replication origins in both bacterial and archaeal genomes based on the Z-curve
method, and the replication origins with manual curation have been collected into
an online database, DoriC. Ori-Finder system and DoriC database are currently
used in the research field of DNA replication origins in prokaryotes, including:
(i) identification of oriC regions in bacterial and archaeal genomes; (ii)
discovery and analysis of the conserved sequences within oriC regions; and (iii)
strand-biased analysis of bacterial genomes.Up to now, more and more predicted
results by Ori-Finder system were supported by subsequent experiments, and Ori
Finder system has been used to identify the replication origins in > 100 newly
sequenced prokaryotes in their genome reports. In addition, the data in DoriC
database have been widely used in the large-scale analyses of replication origins
and strand bias in prokaryotic genomes. Here, we review the development of Ori
Finder system and DoriC database as well as their applications. Some future
directions and aspects for extending the application of Ori-Finder and DoriC are
also presented.
PMID- 29329411
TI - RE: Long-term Safety of Pregnancy Following Breast Cancer According to Estrogen
Receptor Status.
PMID- 29329410
TI - 1918 H1N1 Influenza Virus Replicates and Induces Proinflammatory Cytokine
Responses in Extrarespiratory Tissues of Ferrets.
AB - Background: The 1918 Spanish H1N1 influenza pandemic was the most severe recorded
influenza pandemic with an estimated 20-50 million deaths worldwide. Even though
it is known that influenza viruses can cause extrarespiratory tract complications
which are often severe or even fatal-the potential contribution of
extrarespiratory tissues to the pathogenesis of 1918 H1N1 virus infection has not
been studied comprehensively. Methods: Here, we performed a time-course study in
ferrets inoculated intranasally with 1918 H1N1 influenza virus, with special
emphasis on the involvement of extrarespiratory tissues. Respiratory and
extrarespiratory tissues were collected after inoculation for virological,
histological, and immunological analysis. Results: Infectious virus was detected
at high titers in respiratory tissues and, at lower titers in most
extrarespiratory tissues. Evidence for active virus replication, as indicated by
the detection of nucleoprotein by immunohistochemistry, was observed in the
respiratory tract, peripheral and central nervous system, and liver.
Proinflammatory cytokines were up-regulated in respiratory tissues, olfactory
bulb, spinal cord, liver, heart, and pancreas. Conclusions: 1918 H1N1 virus
spread to and induced cytokine responses in tissues outside the respiratory
tract, which likely contributed to the severity of infection. Moreover, our data
support the suggested link between 1918 H1N1 infection and central nervous system
disease.
PMID- 29329413
TI - Mapping a Filoviral Serologic Footprint in the Democratic Republic of the Congo:
Who Goes There?
PMID- 29329412
TI - Lhx8 ablation leads to massive autophagy of mouse oocytes associated with DNA
damage.
AB - Following proliferation of oogonia in mammals, great numbers of germ cells are
discarded, primarily by apoptosis, while the remainder form primordial follicles
(the ovarian reserve) that determine fertility and reproductive lifespan. More
massive, rapid, and essentially total loss of oocytes, however, occurs when the
transcription factor Lhx8 is ablated-though the cause and mechanism of germ cell
loss from the Lhx8-/- ovaries has been unknown. We found that Lhx8-/- ovaries
maintain the same number of germ cells throughout embryonic development; rapid
decrease in the pool of oocytes starts shortly before birth. The loss results
from activation of autophagy, which becomes overwhelming within the first
postnatal week, with extracellular matrix proteins filling the space previously
occupied by follicles to produce a fibrotic ovary. Associated with this process,
as early as a few days before birth, Lhx8-/- oocytes failed to repair DNA damage
which normally occurs when meiosis is initiated during embryonic development; and
DNA damage repair genes were downregulated throughout the oocyte short lifespan.
Based on gene expression analyses and morphological changes, we propose a model
in which lineage-restricted failure of DNA repair triggers germ cell autophagy,
causing premature depletion of the ovarian reserve in Lhx8-/- mice.
PMID- 29329414
TI - Is big bad or bearable? Long-term renal transplant outcomes in obese recipients.
AB - Background: The global obesity epidemic has implications for kidney
transplantation. There are conflicting reports regarding the impact of obesity on
long-term post-transplant outcomes. Aim: To explore the impact of body mass index
(BMI) on long-term outcomes after kidney transplantation. Design: The association
between BMI and cardiovascular disease, cancer, post-transplant diabetes
mellitus, graft and recipient survival was investigated in recipients who had
been transplanted at least ten years previously. Methods: All consecutive adult
renal transplant recipients who received first, deceased donor, transplants
between 1986 and 2005 in Northern Ireland were followed-up until 2016. Results: A
total of 328 patients were eligible. Of them, 96 were overweight with a BMI 25.0
29.9 kg/m2, and 56 were obese with a BMI exceeding 29.9 kg/m2. Median follow-up
time was 16.7 years. In multivariate analysis recipient BMI was associated with
the development of post-transplant diabetes mellitus (P=0.003), but not with new
cardiovascular disease (P=0.78). Cancer was less common in recipients with a
higher BMI (hazard ratio (HR) 0.58, P < 0.001). BMI at the time of
transplantation did not significantly influence graft (P=0.28) or recipient
survival (P=0.13). Conclusions: Increased BMI at time of transplantation is
associated with an increased risk of post-transplant diabetes mellitus but not
new cardiovascular disease or malignancy. Long-term graft and recipient survival
is not impacted. Potential recipients should not be excluded from transplantation
solely on the basis of obesity, rather it should be considered as one part of an
individualized risk stratification, based on comorbidity and considering the risk
of death on maintenance dialysis.
PMID- 29329415
TI - Establishment of a three-dimensional model to study human uterine angiogenesis.
AB - STUDY QUESTION: Can primary human uterine microvascular endothelial cells
(UtMVECs) be used as a model to study uterine angiogenic responses in vitro that
are relevant in pregnancy? SUMMARY ANSWER: UtMVECs demonstrated angiogenic
responses when stimulated with proangiogenic factors, including sphingosine 1
phosphate (S1P), vascular endothelial growth factor (VEGF), basic fibroblast
growth factor (bFGF), physiological levels of wall shear stress (WSS), human
chorionic gonadotropin (hCG) and various combinations of estrogen and
progesterone. WHAT IS KNOWN ALREADY: During sprouting angiogenesis, signaling
from growth factors and cytokines induces a monolayer of quiescent endothelial
cells (ECs) lining the vasculature to degrade the extracellular matrix and invade
the surrounding tissue to form new capillaries. During pregnancy and the female
reproductive cycle, the uterine endothelium becomes activated and undergoes
sprouting angiogenesis to increase the size and number of blood vessels in the
endometrium. STUDY DESIGN, SIZE, DURATION: The study was designed to examine the
angiogenic potential of primary human UtMVECs using the well-characterized human
umbilical vein EC (HUVEC) line as a control to compare angiogenic potential. ECs
were seeded onto three-dimensional (3D) collagen matrices, supplemented with
known proangiogenic stimuli relevant to pregnancy and allowed to invade for 24 h.
Sprouting responses were analyzed using manual and automated methods for
quantification. PARTICIPANTS/MATERIALS, SETTING, METHODS: RT-PCR, Western blot
analysis and immunostaining were used to characterize UtMVECs. Angiogenic
responses were examined using 3D invasion assays. Western blotting was used to
confirm signaling responses after proangiogenic lipid, pharmacological inhibitor,
and recombinant lentiviral treatments. All experiments were repeated at least
three times. MAIN RESULTS AND THE ROLE OF CHANCE: After ensuring that UtMVECs
expressed the proper endothelial markers, we found that UtMVECs invade 3D
collagen matrices dose-dependently in response to known proangiogenic stimuli
(e.g. S1P, VEGF, bFGF, hCG, estrogen, progesterone and WSS) present during early
pregnancy. Invasion responses were positively correlated with phosphorylation of
phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and p42/p44 mitogen
activated protein kinase (ERK). Inhibition of these second messengers
significantly impaired sprouting (P < 0.01). Gene silencing of membrane type 1
matrix metalloproteinase using multiple approaches completely abrogated sprouting
(P < 0.001). Finally, UtMVECs displayed a unique ability to undergo sprouting in
response to hCG, and combined estrogen and progesterone treatment. LARGE SCALE
DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: The study of uterine
angiogenesis in vitro has limitations and any findings many not fully represent
the in vivo state. However, these experiments do provide evidence for the ability
of UtMVECs to be used in functional sprouting assays in a 3D environment,
stimulated by physiological factors that are produced locally within the uterus
during early pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: We show that UtMVECs
can be used reliably to investigate how growth factors, hormones, lipids and
other factors, such as flow, affect angiogenesis in the uterus. STUDY
FUNDING/COMPETING INTERESTS: This work was supported by NIH award HL095786 to
K.J.B. The authors have no conflicts of interest.
PMID- 29329416
TI - Automatic, electrocardiographic-based detection of autonomic arousals and their
association with cortical arousals, leg movements, and respiratory events in
sleep.
AB - Study Objectives: The current definition of sleep arousals neglects to address
the diversity of arousals and their systemic cohesion. Autonomic arousals (AA)
are autonomic activations often associated with cortical arousals (CA), but they
may also occur in relation to a respiratory event, a leg movement event or
spontaneously, without any other physiological associations. AA should be
acknowledged as essential events to understand and explore the systemic
implications of arousals. Methods: We developed an automatic AA detection
algorithm based on intelligent feature selection and advanced machine learning
using the electrocardiogram. The model was trained and tested with respect to CA
systematically scored in 258 (181 training size/77 test size) polysomnographic
recordings from the Wisconsin Sleep Cohort. Results: A precision value of 0.72
and a sensitivity of 0.63 were achieved when evaluated with respect to CA.
Further analysis indicated that 81% of the non-CA-associated AAs were associated
with leg movement (38%) or respiratory (43%) events. Conclusions: The presented
algorithm shows good performance when considering that more than 80% of the false
positives (FP) found by the detection algorithm appeared in relation to either
leg movement or respiratory events. This indicates that most FP constitute
autonomic activations that are indistinguishable from those with cortical
cohesion. The proposed algorithm provides an automatic system trained in a
clinical environment, which can be utilized to analyze the systemic and clinical
impacts of arousals.
PMID- 29329418
TI - Variability of Late-Night Salivary Cortisol in Cushing Disease: A Prospective
Study.
AB - Background: The frequency of variable hormonogenesis in patients with Cushing
disease (CD) but without cyclical symptoms is unclear. Aim: To assess the
frequency of variable hormonogenesis in patients presenting with CD. Methods:
Over a 6-month period, patients with confirmed or suspected CD provided late
night salivary samples for up to 42 consecutive nights. Results: Of 19 patients
confirmed to have CD, 16 provided at least 7 consecutive salivary samples, and 13
provided at least 21; these 16 patients are the subjects of this report. Twelve
patients had at least three peak and two trough levels of late-night salivary
cortisol (LNSC) but in only two patients were strict criteria for cyclical
hormonogenesis fulfilled; variation was assessed as random in the others. Eight
patients had de novo CD, and eight had recurrent/persistent disease. All patients
with recurrent/persistent CD had two or more normal results, and in four of these
patients, >50% of LNSC were normal. In six patients with de novo disease with at
least one normal LNSC level, the maximum levels ranged from 1.55 to 15.5 times
the upper limit of normal. Conclusions: Extreme fluctuations of cortisol
production, measured by sequential LNSC, are common in CD. In newly diagnosed
disease, this may only occasionally impair diagnostic ability, whereas in most
patients with recurrent/persistent disease after pituitary surgery, LNSC is
frequently within the reference range, with potential to cause diagnostic
problems.
PMID- 29329417
TI - Effects of Alcohol Cues on MRS Glutamate Levels in the Anterior Cingulate.
AB - Growing evidence suggests that glutamate neurotransmission plays a critical role
in alcohol addiction. Cue-induced change of glutamate has been observed in animal
studies but never been investigated in humans. This work investigates cue-induced
change in forebrain glutamate in individuals with alcohol use disorder (AUD). A
total of 35 subjects (17 individuals with AUD and 18 healthy controls)
participated in this study. The glutamate concentration was measured with single
voxel 1H-MR spectroscopy at the dorsal anterior cingulate. Two MRS sessions were
performed in succession, the first to establish basal glutamate levels and the
second to measure the change in response to alcohol cues. The changes in
glutamate were quantified for both AUD subjects and controls. A mixed model ANOVA
and t-tests were performed for statistical analysis. ANOVA revealed a main effect
of cue-induced decrease of glutamate level in the anterior cingulate cortex
(ACC). A significant interaction revealed that only AUD subjects showed
significant decrease of glutamate in the ACC. There were no significant group
differences in the level of basal glutamate. However, a negative correlation was
found between the basal glutamate level and the number of drinking days in the
past 2 weeks for the AUD subjects. Collectively, our results indicate that
glutamate in key areas of the forebrain reward circuit is modulated by alcohol
cues in early alcohol dependence.
PMID- 29329419
TI - A Single Mutation Unlocks Cascading Exaptations in the Origin of a Potent
Pitviper Neurotoxin.
AB - Evolutionary innovations and complex phenotypes seemingly require an improbable
amount of genetic change to evolve. Rattlesnakes display two dramatically
different venom phenotypes. Type I venoms are hemorrhagic with low systemic
toxicity and high expression of tissue-destroying snake venom metalloproteinases.
Type II venoms are highly neurotoxic and lack snake venom metalloproteinase
expression and associated hemorrhagic activity. This dichotomy hinges on Mojave
toxin (MTx), a phospholipase A2 (PLA2) based beta-neurotoxin expressed in Type II
venoms. MTx is comprised of a nontoxic acidic subunit that undergoes extensive
proteolytic processing and allosterically regulates activity of a neurotoxic
basic subunit. Evolution of the acidic subunit presents an evolutionary challenge
because the need for high expression of a nontoxic venom component and the
proteolytic machinery required for processing suggests genetic changes of
seemingly little immediate benefit to fitness. We showed that MTx evolved through
a cascading series of exaptations unlocked by a single nucleotide change. The
evolution of one new cleavage site in the acidic subunit unmasked buried cleavage
sites already present in ancestral PLA2s, enabling proteolytic processing. Snake
venom serine proteases, already present in the venom to disrupt prey hemostasis,
possess the requisite specificities for MTx acidic subunit proteolysis. The
dimerization interface between MTx subunits evolved by exploiting a latent, but
masked, hydrophobic interaction between ancestral PLA2s. The evolution of MTx
through exaptation of existing functional and structural features suggests
complex phenotypes that depend on evolutionary innovations can arise from minimal
genetic change enabled by prior evolution.
PMID- 29329421
TI - Beta-2 microglobulin clearance in high-flux dialysis and convective dialysis
modalities: a meta-analysis of published studies.
PMID- 29329420
TI - Pyrrolidine dithiocarbamate reverses Bcl-xL-mediated apoptotic resistance to
doxorubicin by inducing paraptosis.
AB - Elevated Bcl-xL expression in cancer cells contributes to doxorubicin (DOX)
resistance, leading to failure in chemotherapy. In addition, the clinical use of
high-dose doxorubicin (DOX) in cancer therapy has been limited by issues with
cardiotoxicity and hepatotoxicity. Here, we show that co-treatment with
pyrrolidine dithiocarbamate (PDTC) attenuates DOX-induced apoptosis in Chang-L
liver cells and human hepatocytes, but overcomes DOX resistance in Bcl-xL
overexpressing Chang-L cells and several hepatocellular carcinoma (HCC) cell
lines with high Bcl-xL expression. Additionally, combined treatment with DOX and
PDTC markedly retarded tumor growth in a Huh-7 HCC cell xenograft tumor model,
compared to either mono-treatment. These results suggest that DOX/PDTC co
treatment may provide a safe and effective therapeutic strategy against malignant
hepatoma cells with Bcl-xL-mediated apoptotic defects. We also found that
induction of paraptosis, a cell death mode that is accompanied by dilation of the
endoplasmic reticulum and mitochondria, is involved in this anti-cancer effect of
DOX/PDTC. The intracellular glutathione levels were reduced in Bcl-xL
overexpressing Chang-L cells treated with DOX/PDTC, and DOX/PDTC-induced
paraptosis was effectively blocked by pretreatment with thiol-antioxidants, but
not by non-thiol antioxidants. Collectively, our results suggest that disruption
of thiol homeostasis may critically contribute to DOX/PDTC-induced paraptosis in
Bcl-xL-overexpressing cells.
PMID- 29329422
TI - Proscriptive vs. Prescriptive Health Recommendations to Drink Alcohol Within
Recommended Limits: Effects on Moral Norms, Reactance, Attitudes, Intentions and
Behaviour Change.
AB - Aims: Health advice can be framed in terms of prescriptive rules (what people
should do, e.g. you should drink alcohol within recommended limits) or
proscriptive rules (what people should not do, e.g. you should not drink alcohol
above recommended limits). The current research examines the differing effect
that these two types of injunction have on participants' moral norms, reactance,
attitudes and intentions to consume alcohol within moderation, and their
subsequent alcohol consumption. Methods: Participants (N = 529) completed an
online questionnaire which asked them to report their previous 7 days' alcohol
consumption. They then read either a proscriptive or a prescriptive health
message and completed measures of moral norms, reactance, attitudes and
intentions to drink alcohol only within recommended limits. Subsequent alcohol
consumption was reported 7 days later. Results: The results showed that across
all participants, the proscriptive message elicited stronger moral norms than did
the prescriptive message, which in turn were associated with more positive
attitudes and intentions to drink within recommended limits. For male
participants who reported drinking more alcohol than recommended at baseline, the
proscriptive message elicited more reported alcohol consumption over the
subsequent 7 days. Conclusions: Proscriptive messages may be effective at
eliciting stronger moral norms to drink within government recommended guidelines.
However, reactance may occur for high relevance groups. Practical and theoretical
implications are discussed.
PMID- 29329423
TI - Development and early validation of a patient-reported outcome measure to assess
sleep amongst people experiencing problems with alcohol or other drugs.
AB - Study Objectives: To develop a patient-reported outcome measure to assess sleep
amongst people experiencing problems with alcohol or other drugs. Methods: Item
development included secondary analyses of qualitative interviews with drug or
alcohol users in residential treatment, a review of validated sleep measures,
focus groups with drug or alcohol users in residential treatment, and feedback
from drug or alcohol users recruited from community and residential settings. An
initial version of the measure was completed by 549 current and former drug or
alcohol users (442 in person and 107 online). Analyses comprised classical test
theory methods, exploratory and confirmatory factor analysis, measurement
invariance assessment, and item response theory (IRT). Results: The initial
measure (30 items) had good content and face validity and was named the Substance
Use Sleep Scale (SUSS) by addiction service users. After seven items were removed
due to low item-factor loadings, two factors were retained and labeled: "Mind and
Body Sleep Problems" (14 items) and "Substance-Related Sleep Problems" (nine
items). Measurement invariance was confirmed with respect to gender, age, and
administration format. IRT (information) and classical test theory (internal
consistency and stability) indicated measure reliability. Standard parametric and
nonparametric techniques supported convergent and discriminant validity.
Conclusions: SUSS is an easy-to-complete patient-reported outcome measure of
sleep for people with drug or alcohol problems. It can be used by those concerned
about their own sleep, and by treatment providers and researchers seeking to
better understand, assess, and potentially treat sleep difficulties amongst this
population. Further validity testing with larger and more diverse samples is now
required.
PMID- 29329424
TI - Brassinosteroids regulate pavement cell growth by mediating BIN2-induced
microtubule stabilization.
AB - Brassinosteroids (BRs), a group of plant steroid hormones, play important roles
in regulating plant development. The cytoskeleton also affects key developmental
processes and a deficiency in BR biosynthesis or signaling leads to abnormal
phenotypes similar to those of microtubule-defective mutants. However, how BRs
regulate microtubule and cell morphology remains unknown. Here, using liquid
chromatography-tandem mass spectrometry, we identified tubulin proteins that
interact with Arabidopsis BRASSINOSTEROID INSENSITIVE2 (BIN2), a negative
regulator of BR responses in plants. In vitro and in vivo pull-down assays
confirmed that BIN2 interacts with tubulin proteins. High-speed co-sedimentation
assays demonstrated that BIN2 also binds microtubules. The Arabidopsis genome
also encodes two BIN2 homologs, BIN2-LIKE 1 (BIL1) and BIL2, which function
redundantly with BIN2. In the bin2-3 bil1 bil2 triple mutant, cortical
microtubules were more sensitive to treatment with the microtubule-disrupting
drug oryzalin than in wild-type, whereas in the BIN2 gain-of-function mutant bin2
1, cortical microtubules were insensitive to oryzalin treatment. These results
provide important insight into how BR regulates plant pavement cell and leaf
growth by mediating the stabilization of microtubules by BIN2.
PMID- 29329426
TI - A Practical Guide to Estimating the Heritability of Pathogen Traits.
AB - Pathogen traits, such as the virulence of an infection, can vary significantly
between patients. A major challenge is to measure the extent to which genetic
differences between infecting strains explain the observed variation of the
trait. This is quantified by the trait's broad-sense heritability, H2. A recent
discrepancy between estimates of the heritability of HIV-virulence has opened a
debate on the estimators' accuracy. Here, we show that the discrepancy originates
from model limitations and important lifecycle differences between sexually
reproducing organisms and transmittable pathogens. In particular, current
quantitative genetics methods, such as donor-recipient regression (DR) of
surveyed serodiscordant couples and the phylogenetic mixed model (PMM), are prone
to underestimate H2, because they neglect or do not fit to the loss of
resemblance between transmission partners caused by within-host evolution. In a
phylogenetic analysis of 8,483 HIV patients from the UK, we show that the
phenotypic correlation between transmission partners decays with the amount of
within-host evolution of the virus. We reproduce this pattern in toy-model
simulations and show that a phylogenetic Ornstein-Uhlenbeck model (POUMM)
outperforms the PMM in capturing this correlation pattern and in quantifying H2.
In particular, we show that POUMM outperforms PMM even in simulations without
selection - as it captures the mentioned correlation pattern - which has not been
appreciated until now. By cross-validating the POUMM estimates with ANOVA on
closest phylogenetic pairs (ANOVA-CPP), we obtain H2~0.2, meaning about 20% of
the variation in HIV-virulence is explained by the virus genome both for European
and African data.
PMID- 29329425
TI - Comparison of Hepatic 2D Sandwich Cultures and 3D Spheroids for Long-term
Toxicity Applications: A Multicenter Study.
AB - Primary human hepatocytes (PHHs) are commonly used for in vitro studies of drug
induced liver injury. However, when cultured as 2D monolayers, PHH lose crucial
hepatic functions within hours. This dedifferentiation can be ameliorated when
PHHs are cultured in sandwich configuration (2Dsw), particularly when cultures
are regularly re-overlaid with extracellular matrix, or as 3D spheroids. In this
study, the 6 participating laboratories evaluated the robustness of these 2 model
systems made from cryopreserved PHH from the same donors considering both inter
donor and inter-laboratory variability and compared their suitability for use in
repeated-dose toxicity studies using 5 different hepatotoxins with different
toxicity mechanisms. We found that expression levels of proteins involved in drug
absorption, distribution, metabolism, and excretion, as well as catalytic
activities of 5 different CYPs, were significantly higher in 3D spheroid
cultures, potentially affecting the exposure of the cells to drugs and their
metabolites. Furthermore, global proteomic analyses revealed that PHH in 3D
spheroid configuration were temporally stable whereas proteomes from the same
donors in 2Dsw cultures showed substantial alterations in protein expression
patterns over the 14 days in culture. Overall, spheroid cultures were more
sensitive to the hepatotoxic compounds investigated, particularly upon long-term
exposures, across testing sites with little inter-laboratory or inter-donor
variability. The data presented here suggest that repeated-dosing regimens
improve the predictivity of in vitro toxicity assays, and that PHH spheroids
provide a sensitive and robust system for long-term mechanistic studies of drug
induced hepatotoxicity, whereas the 2Dsw system has a more dedifferentiated
phenotype and lower sensitivity to detect hepatotoxicity.
PMID- 29329427
TI - Ozone-Induced Vascular Contractility and Pulmonary Injury Are Differentially
Impacted by Diets Enriched With Coconut Oil, Fish Oil, and Olive Oil.
AB - Fish, olive, and coconut oil dietary supplementation have several
cardioprotective benefits, but it is not established if they protect against air
pollution-induced adverse effects. We hypothesized that these dietary supplements
would attenuate ozone-induced systemic and pulmonary effects. Male Wistar Kyoto
rats were fed either a normal diet, or a diet supplemented with fish, olive, or
coconut oil for 8 weeks. Animals were then exposed to air or ozone (0.8 ppm), 4
h/day for 2 days. Ozone exposure increased phenylephrine-induced aortic
vasocontraction, which was completely abolished in rats fed the fish oil diet.
Despite this cardioprotective effect, the fish oil diet increased baseline levels
of bronchoalveolar lavage fluid (BALF) markers of lung injury and inflammation.
Ozone-induced pulmonary injury/inflammation were comparable in rats on normal,
coconut oil, and olive oil diets with altered expression of markers in animals
fed the fish oil diet. Fish oil, regardless of exposure, led to enlarged, foamy
macrophages in the BALF that coincided with decreased pulmonary mRNA expression
of cholesterol transporters, cholesterol receptors, and nuclear receptors. Serum
microRNA profile was assessed and demonstrated marked depletion of a variety of
microRNAs in animals fed the fish oil diet, several of which were of splenic
origin. No ozone-specific changes were noted. Collectively, these data indicate
that although fish oil offered vascular protection from ozone exposure, it
increased pulmonary injury/inflammation and impaired lipid transport mechanisms
resulting in foamy macrophage accumulation, demonstrating the need to be
cognizant of potential off-target pulmonary effects that might offset the overall
benefit of this vasoprotective supplement.
PMID- 29329428
TI - Perceived environmental barriers to physical activity in young adults in Dhaka
City, Bangladesh-does gender matter?
AB - Background: Physical activity (PA) has demonstrated health benefits, but
participation is low in many countries. Little is known about environmental
barriers to PA among young Asian adults. The purpose of this study was to
identify common perceived environmental barriers to PA in young adults in Dhaka,
Bangladesh and to examine if these barriers differed by gender. Methods: This was
a cross-sectional study with a self-administered survey and data collected from a
convenience sample of 573 students aged 20.71+/-1.35 years (female 45%) in Dhaka.
Binary logistic regression analysis was used to examine the association between
environmental barriers and gender, adjusting for potential confounders. Results:
Poor street lighting at night (62%) and a lack of convenient places to do PA
(56%) were the most frequently reported environmental barriers to PA. Females
were more likely than males to identify a lack of neighbourhood safety (OR 4.65
[95% CI 3.09-7.00]), poor street lighting (OR 2.82 [95% CI 1.95-4.11]), lack of
convenient places (OR 2.04 [95% CI 1.39-3.00]), unclean and untidy neighbourhood
(OR 1.84 [95% CI 1.25-2.72]) and poor weather (OR 1.61 [95% CI 1.11-2.33]) as
barriers to PA, after adjusting for a set of confounders. Conclusions: Findings
suggest that environmental barriers to PA are particularly salient to young
females in urban Bangladesh. This study underscores the need for safe and
convenient options for PA that are also female friendly.
PMID- 29329429
TI - How to convene an international health or development commission: ten key steps.
AB - The Commission on Investing in Health (CIH), an international group of 25
economists and global health experts, published its Global Health 2035 report in
The Lancet in December 2013. The report laid out an ambitious investment
framework for achieving a "grand convergence" in health-a universal reduction in
deaths from infectious diseases and maternal and child health conditions-within a
generation. This article captures ten key elements that the CIH found important
to its process and successful outcomes. The elements are presented in
chronological order, from inception to post-publication activities. The starting
point is to identify the gap that a new commission could help to narrow. A
critical early step is to choose a chair who can help to set the agenda, motivate
the commissioners, frame the commission's analytic work, and run the commission
meetings in an effective way. In selecting commissioners, important
considerations are their technical expertise, ensuring diversity of people and
viewpoints, and the connections that commissioners have with the intended policy
audience. Financial and human resources need to be secured, typically from
universities, foundations, and development agencies. It is important to set a
clear end date, so that the commission's work program, the timing of its meetings
and its interim deadlines can be established. In-person meetings are usually a
more effective mechanism than conference calls for gaining commissioners' inputs,
surfacing important debates, and 'reality testing' the commission's key findings
and messages. To have policy impact, the commission report should ideally say
something new and unexpected and should have simple messages. Generating new
empirical data and including forward-looking recommendations can also help
galvanize policy action. Finally, the lifespan of a commission can be extended if
it lays the foundation for a research agenda that is then taken up after the
commission report is published.
PMID- 29329431
TI - A Validated Method for the Screening of 320 Forensically Significant Compounds in
Blood by LC/QTOF, with Simultaneous Quantification of Selected Compounds.
AB - A broad drug screening method for toxicologically significant drugs and
metabolites in whole blood using liquid chromatography time-of-flight mass
spectrometry (LC/QTOF) was developed and comprehensively validated. The method
qualitatively screens for 320 compounds while simultaneously quantifying 39.
Compounds were extracted from the blood using alkaline liquid/liquid extraction
and chromatographic separation was achieved in 12 min. The QTOF was operated
using positive mode electrospray ionization using data dependent acquisition.
Qualitative validation was performed for all 320 compounds, and included
selectivity, recovery, limit of detection, matrix effects, carryover and extract
stability. The limits of detection were in the low to sub ng/mL range for the
majority of compounds. Full quantitative validation was performed for 39
compounds and accuracy and precision were within 15 and 18%, respectively. The
qualitative data processing method uses an in-house retention time, accurate mass
and MSMS spectral database, which can be easily updated with new compounds of
interest as they emerge onto the market, without affecting method performance.
The use of a non-targeted data acquisition method coupled with targeted data
processing has proven to be a highly versatile, efficient and robust approach to
screening, well suited to meet the needs of the modern toxicology laboratory
involved in systematic toxicological analysis.
PMID- 29329432
TI - Cardiac surgical strategy for extremely low-birthweight infants with pulmonary
overcirculation.
AB - OBJECTIVES: This study aimed to review the clinical outcomes of staged cardiac
surgery in extremely low-birthweight infants with congenital heart disease and
pulmonary overcirculation. METHODS: Six extremely low-birthweight infants with
congenital heart disease and pulmonary overcirculation underwent staged cardiac
surgery between 2005 and 2017. The median birthweight was 895 g (range 620-990
g), and the median gestational age was 28 weeks (range 23-31 weeks). Clinical
outcomes were evaluated, and we focused on pulmonary haemodynamics. RESULTS:
Pulmonary artery banding or bilateral pulmonary artery banding was performed as
the initial palliation at a median age of 23 days with a median body weight of
880 g. Corrective surgery was performed at a median age of 187 days with a median
body weight of 3.9 kg. All of the patients successfully underwent corrective
surgery and survived to date. Pulmonary hypertension regressed after corrective
surgery in all of the patients, except for 1 patient with severe bronchopulmonary
dysplasia. CONCLUSIONS: Acceptable outcomes can be obtained by staged cardiac
surgery in extremely low-birthweight infants with congenital heart disease and
pulmonary overcirculation. While early pulmonary artery banding can lead to
regression of pulmonary hypertension after corrective surgery, close follow-up is
required.
PMID- 29329430
TI - Increases in IGF-1 After Anti-TNF-alpha Therapy Are Associated With Bone and
Muscle Accrual in Pediatric Crohn Disease.
AB - Context: Low levels of insulinlike growth factor 1 (IGF-1) in pediatric and
adolescent Crohn disease (CD) likely contribute to bone and muscle deficits.
Objective: Assess changes in IGF-1 levels and associations with bone and muscle
accrual following initiation of anti-tumor necrosis factor alpha (TNF-alpha)
therapy in pediatric and adolescent CD. Design and Participants: Participants (n
= 75, age 5 to 21 years) with CD were enrolled in a prospective cohort study; 63
completed the 12-month visit. Main Outcome Measures: IGF-1 levels at baseline and
10 weeks, as well as dual-energy x-ray absorptiometry (DXA) and tibia peripheral
quantitative computed tomography (pQCT) measures of bone and muscle at baseline
and 12 months after initiation of anti-TNF-alpha therapy. Outcomes were expressed
as sex-specific z scores. Results: IGF-1 z scores increased from a median
(interquartile range) of -1.0 (-1.58 to -0.17) to -0.36 (-1.04 to 0.36) over 10
weeks (P < 0.001). Lesser disease severity and systemic inflammation, as well as
greater estradiol z scores (in girls), was significantly associated with greater
IGF-1 z scores over time. DXA whole-body bone mineral content, leg lean mass, and
total hip and femoral neck bone mineral density (BMD) z scores were low at
baseline (P < 0.0001 vs reference data) and increased significantly (P < 0.001)
over 12 months. Greater increases in IGF-1 z scores over 10 weeks predicted
improvement in DXA bone and muscle outcomes and pQCT trabecular BMD and cortical
area. Adjustment for changes in muscle mass markedly attenuated the associations
between IGF-1 levels and bone outcomes. Conclusions: Short-term improvements in
IGF-1 z scores predicted recovery of bone and muscle outcomes following
initiation of anti-TNF-alpha therapy in pediatric CD. These data suggest that
disease effects on growth hormone metabolism contribute to musculoskeletal
deficits in CD.
PMID- 29329433
TI - RAGE mediates Abeta accumulation in a mouse model of Alzheimer's disease via
modulation of beta- and gamma-secretase activity.
AB - Receptor for Advanced Glycation End products (RAGE) has been implicated in
amyloid beta-peptide (Abeta)-induced perturbation relevant to the pathogenesis of
Alzheimer's disease (AD). However, whether and how RAGE regulates Abeta
metabolism remains largely unknown. Abeta formation arises from aberrant cleavage
of amyloid pre-cursor protein (APP) by beta- and gamma-secretase. To investigate
whether RAGE modulates beta- and gamma-secretase activity potentiating Abeta
formation, we generated mAPP mice with genetic deletion of RAGE (mAPP/RO). These
mice displayed reduced cerebral amyloid pathology, inhibited aberrant APP-Abeta
metabolism by reducing beta- and gamma-secretases activity, and attenuated
impairment of learning and memory compared with mAPP mice. Similarly, RAGE signal
transduction deficient mAPP mice (mAPP/DN-RAGE) exhibited the reduction in
Abeta40 and Abeta42 production and decreased beta-and gamma-secretase activity
compared with mAPP mice. Furthermore, RAGE-deficient mAPP brain revealed
suppression of activation of p38 MAP kinase and glycogen synthase kinase 3beta
(GSK3beta). Finally, RAGE siRNA-mediated gene silencing or DN-RAGE-mediated
signaling deficiency in the enriched human APP neuronal cells demonstrated
suppression of activation of GSK3beta, accompanied with reduction in Abeta levels
and decrease in beta- and gamma-secretases activity. Our findings highlight that
RAGE-dependent signaling pathway regulates beta- and gamma-secretase cleavage of
APP to generate Abeta, at least in part through activation of GSK3beta and p38
MAP kinase. RAGE is a potential therapeutic target to limit aberrant APP-Abeta
metabolism in halting progression of AD.
PMID- 29329434
TI - Effect of mechanical stress on magnetic resonance imaging of the sacroiliac
joints: assessment of military recruits by magnetic resonance imaging study.
PMID- 29329435
TI - Expanding a radiology lexicon using contextual patterns in radiology reports.
AB - Objective: Distributional semantics algorithms, which learn vector space
representations of words and phrases from large corpora, identify related terms
based on contextual usage patterns. We hypothesize that distributional semantics
can speed up lexicon expansion in a clinical domain, radiology, by unearthing
synonyms from the corpus. Materials and Methods: We apply word2vec, a
distributional semantics software package, to the text of radiology notes to
identify synonyms for RadLex, a structured lexicon of radiology terms. We
stratify performance by term category, term frequency, number of tokens in the
term, vector magnitude, and the context window used in vector building. Results:
Ranking candidates based on distributional similarity to a target term results in
high curation efficiency: on a ranked list of 775 249 terms, >50% of synonyms
occurred within the first 25 terms. Synonyms are easier to find if the target
term is a phrase rather than a single word, if it occurs at least 100* in the
corpus, and if its vector magnitude is between 4 and 5. Some RadLex categories,
such as anatomical substances, are easier to identify synonyms for than others.
Discussion: The unstructured text of clinical notes contains a wealth of
information about human diseases and treatment patterns. However, searching and
retrieving information from clinical notes often suffer due to variations in how
similar concepts are described in the text. Biomedical lexicons address this
challenge, but are expensive to produce and maintain. Distributional semantics
algorithms can assist lexicon curation, saving researchers time and money.
PMID- 29329436
TI - Development of the place-based Adelante social marketing campaign for prevention
of substance use, sexual risk and violence among Latino immigrant youth.
AB - Immigrant Latino youth represent a high-risk subgroup that should be targeted
with health promotion efforts. However, there are considerable barriers to
engagement in health-related programming. Little is known about the engagement
possibilities of social marketing campaigns and digital strategies for
traditionally 'hard-to-reach' immigrants, underscoring the importance of testing
these techniques with immigrant Latino adolescents. We developed and piloted a
place-based social marketing campaign in coordination with the branded, Positive
Youth Development-based (PYD) Adelante intervention targeting risk factors for co
occurring youth substance abuse, sexual risk and violence. Building on prior
research, we conducted a four-phase formative research process, and planned the
Adelante social marketing campaign based on findings from one group interview and
ongoing consultation with Adelante staff (n=8) and four focus groups with youth
(n=35). Participants identified four overarching campaign themes, and suggested
portrayal of resilient, proud youth who achieved goals despite adversity. Youth
guided selection of campaign features and engagement strategies, including
message/visual content, stylistic elements, and a mixed language approach. We
developed a 12-month campaign to be delivered via print ads, multi-platform
social media promotion, contests, youth-generated videos, blog posts, and text
messaging. We describe the process and outcome of campaign development and make
recommendations for future campaigns.
PMID- 29329437
TI - Association of extracellular dNTP utilization with a GmPAP1-like protein
identified in cell wall proteomic analysis of soybean roots.
AB - Plant root cell walls are dynamic systems that serve as the first plant
compartment responsive to soil conditions, such as phosphorus (P) deficiency. To
date, evidence for the regulation of root cell wall proteins (CWPs) by P
deficiency remains sparse. In order to gain a better understanding of the roles
played by CWPs in the roots of soybean (Glycine max) in adaptation to P
deficiency, we conducted an iTRAQ (isobaric tag for relative and absolute
quantitation) proteomic analysis. A total of 53 CWPs with differential
accumulation in response to P deficiency were identified. Subsequent qRT-PCR
analysis correlated the accumulation of 21 of the 27 up-regulated proteins, and
eight of the 26 down-regulated proteins with corresponding gene expression
patterns in response to P deficiency. One up-regulated CWP, purple acid
phosphatase 1-like (GmPAP1-like), was functionally characterized. Phaseolus
vulgaris transgenic hairy roots overexpressing GmPAP1-like displayed an increase
in root-associated acid phosphatase activity. In addition, relative growth and P
content were significantly enhanced in GmPAP1-like overexpressing lines compared
to control lines when deoxy-ribonucleotide triphosphate (dNTP) was applied as the
sole external P source. Taken together, the results suggest that the modulation
of CWPs may regulate complex changes in the root system in response to P
deficiency, and that the cell wall-localized GmPAP1-like protein is involved in
extracellular dNTP utilization in soybean.
PMID- 29329438
TI - Patient perspectives on how physicians communicate diagnostic uncertainty: An
experimental vignette study.
AB - Objective: We evaluated the effects of three different strategies for
communicating diagnostic uncertainty on patient perceptions of physician
competence and visit satisfaction. Design/Setting: Experimental vignette-based
study design involving pediatric cases presented to a convenience sample of
parents living in a large US city. Participants/Intervention(s): Three vignettes
were developed, each describing one of three different ways physicians
communicated diagnostic uncertainty to parents-(i) explicit expression of
uncertainty ('not sure' about diagnosis), (ii) implicit expression of uncertainty
using broad differential diagnoses and (iii) implicit expression of uncertainty
using 'most likely' diagnoses. Participants were randomly assigned to one of the
three vignettes and then answered a 37-item web-based questionnaire. Main Outcome
Measure(s): Outcome variables included parent-perceived technical competence of
physician, trust and confidence, visit satisfaction and adherence to physician
instructions. Differences between the three groups were compared using analysis
of variance, followed by individual post hoc analyses with Bonferroni correction.
Results: Seventy-one participants completed the vignette questions. Demographic
characteristics and scores on activation (parent activation measure [PAM]) and
intolerance to uncertainty were similar across the three groups. Explicit
expression of uncertainty was associated with lower perceived technical
competence, less trust and confidence, and lower patient adherence as compared to
the two groups with implicit communication. These latter two groups had
comparable outcomes. Conclusion: Parents may react less negatively in terms of
perceived competence, physician confidence and trust, and intention to adhere
when diagnostic uncertainty is communicated using implicit strategies, such as
using broad differential diagnoses or most likely diagnoses. Evidence-based
strategies to communicate diagnostic uncertainty to patients need further
development.
PMID- 29329440
TI - Executive Function and Internalizing Symptoms in Adolescents and Young Adults
With Congenital Heart Disease: The Role of Coping.
AB - Objective: Executive functioning deficits have been documented among congenital
heart disease (CHD) survivors and may contribute to emotional distress. Little
research has investigated the role of coping in this association. This study
examined the role of coping in accounting for the association between self
reported executive function problems and internalizing symptoms among adolescents
and emerging adults (AEAs), as well as young adults (YAs) with CHD. Methods:
Participants included 74 AEA (Mage = 19.32 +/- 3.47 years, range 15-25 years) and
98 YA CHD survivors (Mage = 32.00 +/- 3.69 years, range 26-39 years), recruited
from pediatric and adult outpatient cardiology clinics. Participants completed
self-report measures of executive function problems, coping (primary control,
secondary control, and disengagement coping), and internalizing symptoms. Lesion
severity classification and functional impairment due to symptoms of heart
failure were determined from medical chart review. Results: Significant problems
in executive function were reported by 5% of AEA and 13% of YA. Coping was not
associated with executive function problems or internalizing symptoms for AEA.
However, among YA, less use of adaptive coping strategies and more maladaptive
coping responses was associated with both more executive function problems and
internalizing symptoms. An indirect effect of executive function problems on
internalizing symptoms via secondary control coping emerged for YA. Conclusions:
Executive function problems may disrupt the ability to use important adaptive
coping skills, such as cognitive reappraisal, positive thinking, and acceptance,
thereby resulting in greater emotional distress among YA CHD survivors.
PMID- 29329441
TI - Aging and the Social Ecology of Everyday Interpersonal Perception: What is
Perceived, in Whom, and Where?
AB - Objectives: Despite a proliferation of research in interpersonal perception and
aging, no research has identified the nature of the social and emotional
perceptions made by aging individuals in everyday life. In this study, we aimed
to identify the social ecological features that characterize everyday
interpersonal perception across the adult lifespan. Method: Three studies were
conducted. Study 1 identified and compared the targets and locations of young,
middle-age, and older adults' everyday interpersonal perceptions; these
perceptions were categorized into types in Study 2. Study 3 applied these
categorizations to identify and compare the social ecology surrounding aging
individuals' interpersonal perceptions. Results: Everyday interpersonal
perceptions were directed toward familiar others and occurred in familiar
locations, although the specific familiar targets and locations sometimes varied
significantly with age. However, the types of perceptions made in everyday life
did not vary significantly between age groups. Discussion: Aging individuals make
similar types of interpersonal judgments, but the targets and locations of these
judgments may change with age. Future studies on interpersonal perception and
aging will need to account for these features of the aging individual's social
ecology to provide an accurate assessment of the aging process.
PMID- 29329439
TI - Conserved Proteins of the RNA Interference System in the Arbuscular Mycorrhizal
Fungus Rhizoglomus irregulare Provide New Insight into the Evolutionary History
of Glomeromycota.
AB - Horizontal gene transfer (HGT) is an important mechanism in the evolution of many
living organisms particularly in Prokaryotes where genes are frequently dispersed
between taxa. Although, HGT has been reported in Eukaryotes, its accumulative
effect and its frequency has been questioned. Arbuscular mycorrhizal fungi (AMF)
are an early diverged fungal lineage belonging to phylum Glomeromycota, whose
phylogenetic position is still under debate. The history of AMF and land plant
symbiosis dates back to at least 460 Ma. However, Glomeromycota are estimated to
have emerged much earlier than land plants. In this study, we surveyed genomic
and transcriptomic data of the model arbuscular mycorrhizal fungus Rhizoglomus
irregulare (synonym Rhizophagus irregularis) and its relatives to search for
evidence of HGT that occurred during AMF evolution. Surprisingly, we found a
signature of putative HGT of class I ribonuclease III protein-coding genes that
occurred from autotrophic cyanobacteria genomes to R. irregulare. At least one of
two HGTs was conserved among AMF species with high levels of sequence similarity.
Previously, an example of intimate symbiosis between AM fungus and cyanobacteria
was reported in the literature. Ribonuclease III family enzymes are important in
small RNA regulation in Fungi together with two additional core proteins
(Argonaute/piwi and RdRP). The eukaryotic RNA interference system found in AMF
was conserved and showed homology with high sequence similarity in
Mucoromycotina, a group of fungi closely related to Glomeromycota. Prior to this
analysis, class I ribonuclease III has not been identified in any eukaryotes. Our
results indicate that a unique acquisition of class I ribonuclease III in AMF is
due to a HGT event that occurred from cyanobacteria to Glomeromycota, at the
latest before the divergence of the two Glomeromycota orders Diversisporales and
Glomerales.
PMID- 29329442
TI - Conventional Radiofrequency Thermocoagulation vs Pulsed Radiofrequency
Neuromodulation of Ganglion Impar in Chronic Perineal Pain of Nononcological
Origin.
AB - Background: Chronic nononcological perineal pain has been effectively managed by
ganglion Impar block. Chemical neurolysis, cryoablation, and radiofrequency
ablation have been the accepted methods of blockade. Recently, pulsed
radiofrequency, a novel variant of conventional radiofrequency, has been used for
this purpose. Study Design: This was a prospective, randomized, double-blind
study. Setting: Two different interventional pain management centers in India.
Objective: To compare the efficacy of conventional radiofrequency and pulsed
radiofrequency for gangliom Impar block. Methods: The patients were randomly
allocated to one of two groups. In the conventional radiofrequency (CRF) group (N
= 34), conventional radiofrequency ablation was done, and in the PRF pulsed
radiofrequency (PRF) group (N = 31), pulsed radiofrequency ablation was done.
After informed and written consent, fluoroscopy-guided ganglion Impar block was
performed through the first intracoccygeal approach. The extent of pain relief
was assessed by visual analog scale (VAS) at 24 hours, and at the first, third,
and sixth weeks following the intervention. A questionnaire to evaluate
subjective patient satisfaction was also used at each follow-up visit. Results:
In the CRF group, the mean VAS score decreased significantly from the baseline
value at each follow-up visit. But in the PRF group, this decrease was
insignificant except at 24-hour follow-up. Intergroup comparison also showed
significantly better pain relief in the CRF group as compared with the PRF group.
At the end of follow-up, 28 patients (82%) in the CRF group and four patients
(13%) in the PRF group had excellent results, as assessed by the subjective
patient satisfaction questionnaire. There was no complication in any patient of
either study group, except for short-lived infection at the site of skin puncture
in a few. Conclusion: Ganglion Impar block by conventional radiofrequency
provided a significantly better quality of pain relief with no major side effects
in patients with chronic nononcological perineal pain as compared with pulsed
radiofrequency. Limitations: The short-term follow-up period of only six weeks
was a major drawback associated with this study.
PMID- 29329444
TI - Prevention of IVR: a need for investigation.
AB - Intravesical recurrence (IVR) after RNU for UTUC is a frequent event, occurring
in 20-50% of patients, mostly in the first postoperative year. Several
retrospective studies have shown that predictors of IVR include clinical
characteristics, surgical features and as well pathological characteristics
(previous history of bladder cancer, pathological stage, lymph node involvement,
cis, endoscopic distal ureter, etc.) management. Two prospective studies provide
level I evidence for the safety and efficacy of intravesical single postoperative
chemotherapy for patients treated with radical nephroureterectomy (RNU) for UTUC
in order to prevent IVR. However, some questions remain unanswered. Yamashita et
al. in the current issue of the journal have shown that early ureteral ligation
during RNU decreases the risk of IVR in patients with pelvycalyceal upper tract
urothelial carcinoma. This study despite its limitations represent a step towards
improved outcomes for our patients with UTUC, the relatively low morbidity of the
procedure added to the potential benefit associated with this early ligation make
it an easy implementation in daily practice.
PMID- 29329445
TI - Author's reply to 'Prevention of IVR: a need for investigation'.
PMID- 29329443
TI - Bone formation in ankylosing spondylitis during anti-tumour necrosis factor
therapy imaged by 18F-fluoride positron emission tomography.
AB - Objectives: Excessive bone formation is an important hallmark of AS. Recently it
has been demonstrated that axial bony lesions in AS patients can be visualized
using 18F-fluoride PET-CT. The aim of this study was to assess whether 18F
fluoride uptake in clinically active AS patients is related to focal bone
formation in spine biopsies and is sensitive to change during anti-TNF treatment.
Methods: Twelve anti-TNF-naive AS patients [female 7/12; age 39 years (SD 11);
BASDAI 5.5 +/- 1.1] were included. 18 F-fluoride PET-CT scans were performed at
baseline and in two patients, biopsies were obtained from PET-positive and PET
negative spine lesions. The remaining 10 patients underwent a second 18F-fluoride
PET-CT scan after 12 weeks of anti-TNF treatment. PET scans were scored visually
by two blinded expert readers. In addition, 18F-fluoride uptake was quantified
using the standardized uptake value corrected for individual integrated whole
blood activity concentration (SUVAUC). Clinical response to anti-TNF was defined
according to a ? 20% improvement in Assessment of SpondyloArthritis international
Society criteria at 24 weeks. Results: At baseline, all patients showed at least
one axial PET-positive lesion. Histological analysis of PET-positive lesions in
the spine confirmed local osteoid formation. PET-positive lesions were found in
the costovertebral joints (43%), facet joints (23%), bridging syndesmophytes
(20%) and non-bridging vertebral lesions (14%) and in SI joints (75%). After 12
weeks of anti-TNF treatment, 18F-fluoride uptake in clinical responders decreased
significantly in the costovertebral (mean SUVAUC -1.0; P < 0.001) and SI joints
(mean SUVAUC -1.2; P = 0.03) in contrast to non-responders. Conclusions: 18F
fluoride PET-CT identified bone formation, confirmed by histology, in the spine
and SI joints of AS patients and demonstrated alterations in bone formation
during anti-TNF treatment.
PMID- 29329446
TI - Standardisation of the in vitro comet assay: influence of lysis time and lysis
solution composition on the detection of DNA damage induced by X-rays.
AB - The alkaline comet assay, in vivo and in vitro, is currently used in several
areas of research and in regulatory genotoxicity testing. Several efforts have
been made in order to decrease the inter-experimental and inter-laboratory
variability and increase the reliability of the assay. In this regard, lysis
conditions are considered as one of the critical variables and need to be further
studied. Here, we tested different times of lysis (from no lysis to 1 week) and
two different lysis solutions in human lymphoblast (TK6) cells unexposed or
exposed to X-rays. Similar % tail DNA values were obtained independently of the
time of lysis employed for every X-ray dose tested and both lysis solutions.
These results, taken together with our previous ones with methyl methanesulfonate
and H2O2, which showed clear lysis-time dependence, support that the influence of
the lysis time in the comet assay results depends on the type of lesion being
detected; some DNA lesions may spontaneously give rise to apurinic or
apyrimidinic (AP) sites during the lysis period, which can be converted into
strand breaks detectable with the comet assay. Testing different times of lysis
would be useful to increase the sensitivity of the comet assay and to ensure the
detection of DNA lesions of an unknown compound, thereby providing some insight
into the chemical nature of the lesions induced. However, the same lysis
conditions (i.e. lysis time and lysis solution) should be used when comparing
results between different experiments or laboratories.
PMID- 29329447
TI - Congenital Hyperinsulinism and Hypopituitarism Attributable to a Mutation in
FOXA2.
AB - Context: Persistent hypoglycemia in the newborn period most commonly occurs as a
result of hyperinsulinism. The phenotype of hypoketotic hypoglycemia can also
result from pituitary hormone deficiencies, including growth hormone and
adrenocorticotropic hormone deficiency. Forkhead box A2 (Foxa2) is a
transcription factor shown in mouse models to influence insulin secretion by
pancreatic beta cells. In addition, Foxa2 is involved in regulation of pituitary
development, and deletions of FOXA2 have been linked to panhypopituitarism.
Objective: To describe an infant with congenital hyperinsulinism and
hypopituitarism as a result of a mutation in FOXA2 and to determine the
functional impact of the identified mutation. Main Outcome Measure: Difference in
wild-type (WT) vs mutant Foxa2 transactivation of target genes that are critical
for beta cell function (ABCC8, KNCJ11, HADH) and pituitary development (GLI2,
NKX2-2, SHH). Results: Transactivation by mutant Foxa2 of all genes studied was
substantially decreased compared with WT. Conclusions: We report a mutation in
FOXA2 leading to congenital hyperinsulinism and hypopituitarism and provide
functional evidence of the molecular mechanism responsible for this phenotype.
PMID- 29329449
TI - Lack of Receptor for Advanced Glycation End Products Leads to Less Severe
Staphylococcal Skin Infection but More Skin Abscesses and Prolonged Wound
Healing.
AB - Background: Lack of receptor for advanced glycation end products (RAGE)
ameliorates several infections including Staphylococcus aureus pneumonia. We
sought to investigate the role of RAGE in staphylococcal skin infection in mice.
Methods: Wild-type (WT) and RAGE deficient (RAGE-/-) mice were subcutaneously
inoculated with S. aureus SH1000 strain in abscess-forming dose or necrotic dose.
Clinical signs of dermatitis, along with histopathological changes, were compared
between the groups. Results: The skin lesion size was smaller in RAGE-/- mice.
Infected RAGE-/- mice expressed lower proinflammatory cytokines in local skins
compared to control mice. Low dose of bacteria caused more abscess formation in
RAGE-/- mice compared to skin necrosis that was more often observed in WT mice.
As a result of more abscess formation, the wound healing was prolonged in RAGE-/-
mice. Importantly, RAGE-/- mice had lower bacterial loads in the skin than
controls, which is correlated with higher local levels of myeloperoxidase before
skin infection. In vitro, enhanced phagocytic capacity of neutrophils and
macrophages obtained from RAGE-/- mice compared to control mice was observed.
Conclusions: RAGE deficiency up-regulates phagocytic capacity of phagocytes,
resulting in lower bacterial burden in local skin and milder skin lesions in mice
with staphylococcal skin infection.
PMID- 29329448
TI - The Prevalence and Management of Dehydration amongst Neonatal Admissions to
General Paediatric Wards in Kenya-A Clinical Audit.
AB - An audit of randomly selected case records of 810 patients admitted to 13
hospitals between December 2015 and November 2016 was done. Prevalence of
dehydration was 19.7% (2293 of 11 636) [95% CI: 17.1-22.6%], range across
hospitals was 9.4% to 27.0%. Most cases with dehydration were clinically
diagnosed (82 of 153; 53.6%), followed by excessive weight loss (54 of 153;
35.3%) and abnormal urea/electrolytes/creatinine (23 of 153; 15.0%).
Documentation of fluids prescribed was poor but, where data were available,
Ringers lactate (30 of 153; 19.6%) and 10% dextrose (18 of 153; 11.8%) were
mostly used. Only 17 of 153 (11.1%) children had bolus fluid prescription, and
Ringer's lactate was most commonly used for bolus at a median volume per kilogram
body weight of 20 ml/kg (interquartile range, 12-30 ml/kg). Neonatal dehydration
is common, but current documentation may underestimate the burden. Heterogeneity
in practice likely reflects the absence of guidelines that in turn reflects a
lack of research informing practical treatment guidelines.
PMID- 29329450
TI - DEVELOPMENT OF HETEROGENEOUS PROPORTIONAL COUNTERS FOR NEUTRON DOSIMETRY.
AB - The use of a custom-made cylindrical graphite proportional counter (Cy-GPC) along
with a cylindrical tissue equivalent proportional counter (TEPC) for neutron
gamma mixed-field dosimetry has been studied in the following steps: first, the
consistency of the gamma dose measurement between the Cy-TEPC and the Cy-GPC was
investigated over a range of 20 keV (X-ray) to 0.661 MeV (Cs-137 gamma ray).
Then, with both the counters used simultaneously, the neutron and gamma ray doses
produced by a P385 Neutron Generator (Thermo Fisher Scientific) together with a
Cs-137 gamma source were determined.
PMID- 29329452
TI - Comment on "Response assessment in medulloblastoma and leptomeningeal seeding
tumors: recommendations from the Response Assessment in Pediatric Neuro-Oncology
Committee".
PMID- 29329453
TI - Response to Harreld re: "Response assessment in medulloblastoma and
leptomeningeal seeding tumors: recommendations from the Response Assessment in
Pediatric Neuro-Oncology Committee".
PMID- 29329451
TI - Epidermal Growth Factor Receptor Signaling Disruption by Endocrine and Metabolic
Disrupting Chemicals.
AB - The purpose of this study is to identify an environmentally relevant shared
receptor target for endocrine and metabolism disrupting chemical pollutants. A
feature of the tested chemicals was that they induced Cyp2b10 in vivo implicating
activation of the constitutive androstane receptor (CAR). Recent studies suggest
that these compounds could be indirect CAR activators via epidermal growth factor
receptor (EGFR) inhibition. Assays included a CAR activity reporter assay, EGF
endocytosis assay, and EGFR phosphorylation assay. Docking simulations were used
to identify putative binding sites for environmental chemicals on the EGFR. Whole
weight and lipid-adjusted serum mean pollutant exposures were determined using
data from the National Health and Examination Survey (NHANES) and compared with
the IC50 values determined in vitro. Chlordane, trans-nonachlor, PCB-126, PCB
153, and atrazine were the most potent EGFR inhibitors tested. PCB-126, PCB-153,
and trans-nonachlor appeared to be competitive EGFR antagonists as they displaced
bound EGF from EGFR. However, atrazine acted through a different mechanism and
could be an EGFR tyrosine kinase inhibitor. EGFR inhibition relative effect
potencies were determined for these compounds. In NHANES, serum concentrations of
trans-nonachlor, PCB-126, and PCB-153 greatly exceeded their calculated IC50
values. A common mechanism of action through EGFR inhibition for three diverse
classes of metabolic disrupting chemicals was characterized by measuring
inhibition of EGFR phosphorylation and EGF-EGFR endocytosis. Based on NHANES
data, EGFR inhibition may be an environmentally relevant mode of action for some
PCBs, pesticides, and herbicides.
PMID- 29329454
TI - A change at the helm of Neuro-Oncology.
PMID- 29329455
TI - Serologic Evidence of Ebolavirus Infection in a Population With No History of
Outbreaks in the Democratic Republic of the Congo.
AB - Background: Previous studies suggest that cases of Ebola virus disease (EVD) may
go unreported because they are asymptomatic or unrecognized, but evidence is
limited by study designs and sample size. Methods: A large population-based
survey was conducted (n = 3415) to assess animal exposures and behaviors
associated with Ebolavirus antibody prevalence in rural Kasai Oriental province
of the Democratic Republic of Congo (DRC). Fourteen villages were randomly
selected and all healthy individuals >=1 year of age were eligible. Results:
Overall, 11% of subjects tested positive for Zaire Ebolavirus (EBOV)
immunoglobulin G antibodies. Odds of seropositivity were higher for study
participants older than 15 years of age and for males. Those residing in Kole
(closer to the outbreak site) tested positive at a rate 1.6* higher than Lomela,
with seropositivity peaking at a site located between Kole and Lomela.
Multivariate analyses of behaviors and animal exposures showed that visits to the
forest or hunting and exposure to rodents or duikers predicted a higher
likelihood of EBOV seropositivity. Conclusions: These results provide serologic
evidence of Ebolavirus exposure in a population residing in non-EBOV outbreak
locations in the DRC and define statistically significant activities and animal
exposures that associate with EBOV seropositivity.
PMID- 29329456
TI - Designing and evaluating an automated system for real-time medication
administration error detection in a neonatal intensive care unit.
AB - Background: Timely identification of medication administration errors (MAEs)
promises great benefits for mitigating medication errors and associated harm.
Despite previous efforts utilizing computerized methods to monitor medication
errors, sustaining effective and accurate detection of MAEs remains challenging.
In this study, we developed a real-time MAE detection system and evaluated its
performance prior to system integration into institutional workflows. Methods:
Our prospective observational study included automated MAE detection of 10 high
risk medications and fluids for patients admitted to the neonatal intensive care
unit at Cincinnati Children's Hospital Medical Center during a 4-month period.
The automated system extracted real-time medication use information from the
institutional electronic health records and identified MAEs using logic-based
rules and natural language processing techniques. The MAE summary was delivered
via a real-time messaging platform to promote reduction of patient exposure to
potential harm. System performance was validated using a physician-generated gold
standard of MAE events, and results were compared with those of current practice
(incident reporting and trigger tools). Results: Physicians identified 116 MAEs
from 10 104 medication administrations during the study period. Compared to
current practice, the sensitivity with automated MAE detection was improved
significantly from 4.3% to 85.3% (P = .009), with a positive predictive value of
78.0%. Furthermore, the system showed potential to reduce patient exposure to
harm, from 256 min to 35 min (P < .001). Conclusions: The automated system
demonstrated improved capacity for identifying MAEs while guarding against alert
fatigue. It also showed promise for reducing patient exposure to potential harm
following MAE events.
PMID- 29329457
TI - A novel application of RNase H2-dependent quantitative PCR for detection and
quantification of Grosmannia clavigera, a mountain pine beetle fungal symbiont,
in environmental samples.
AB - Mountain pine beetle (Dendroctonus ponderosae Hopkins; MPB) is an economically
and ecologically important pest of pine species in western North America.
Mountain pine beetles form complex multipartite relationships with microbial
partners, including the ophiostomoid fungi Grosmannia clavigera (Robinson-Jeffrey
and Davidson) Zipfel, de Beer and Wingfield, Ophiostoma montium (Rumbold) von
Arx, Grosmannia aurea (Robinson-Jeffrey and Davidson) Zipfel, de Beer and
Wingfield, Leptographium longiclavatum (Lee, Kim, and Breuil) and Leptographium
terebrantis (Barras and Perry). These fungi are vectored by MPB to new pine
hosts, where the fungi overcome host defenses to grow into the sapwood. A tree's
relative susceptibility to these fungi is conventionally assessed by measuring
lesions that develop in response to fungal inoculation. However, these lesions
represent a symptom of infection, representing both fungal growth and tree
defense capacity. In order to more objectively assess fungal virulence and host
tree susceptibility in studies of host-pathogen interactions, a reliable,
consistent, sensitive method is required to accurately identify and quantify MPB
associated fungal symbionts in planta. We have adapted RNase H2-dependent PCR, a
technique originally designed for rare allele discrimination, to develop a novel
RNase H2-dependent quantitative PCR (rh-qPCR) assay that shows greater
specificity and sensitivity than previously published PCR-based methods to
quantify MPB fungal symbionts in pine xylem and MPB whole beetles. Two sets of
assay probes were designed: one that amplifies a broad range of ophiostomoid
species, and a second that amplifies G. clavigera but not other MPB-associated
ophiostomoid species. Using these primers to quantify G. clavigera in pine stems,
we provide evidence that lesion length does not accurately reflect the extent of
fungal colonization along the stem nor the quantity of fungal growth within this
colonized portion of stem. The sensitivity, specificity, reproducibility, cost
effectiveness and high-throughput potential of the rh-qPCR assay makes the
technology suitable for identification and quantification of a wide array of
pathogenic and beneficial microbes that form associations with plants and other
organisms, even when the microbial partner is present in low abundance.
PMID- 29329459
TI - Using Pool-seq to Search for Genomic Regions Affected by Hybrid Inviability in
the copepod T. californicus.
AB - The formation of reproductive barriers between allopatric populations involves
the accumulation of incompatibilities that lead to intrinsic postzygotic
isolation. The evolution of these incompatibilities is usually explained by the
Dobzhansky-Muller model, where epistatic interactions that arise within the
diverging populations, lead to deleterious interactions when they come together
in a hybrid genome. These incompatibilities can lead to hybrid inviability,
killing individuals with certain genotypic combinations, and causing the
population's allele frequency to deviate from Mendelian expectations.
Traditionally, hybrid inviability loci have been detected by genotyping
individuals at different loci across the genome. However, this method becomes
time consuming and expensive as the number of markers or individuals increases.
Here, we test if a Pool-seq method can be used to scan the genome of F2 hybrids
to detect genomic regions that are affected by hybrid inviability. We survey the
genome of hybrids between 2 populations of the copepod Tigriopus californicus,
and show that this method has enough power to detect even small changes in allele
frequency caused by hybrid inviability. We show that allele frequency estimates
in Pool-seq can be affected by the sampling of alleles from the pool of DNA
during the library preparation and sequencing steps and that special
considerations must be taken when aligning hybrid reads to a reference when the
populations/species are divergent.
PMID- 29329458
TI - Three Fatty Acyl-Coenzyme A Reductases, BdFAR1, BdFAR2 and BdFAR3, are Involved
in Cuticular Wax Primary Alcohol Biosynthesis in Brachypodium distachyon.
AB - Plant cuticular wax is a heterogeneous mixture of very long chain fatty acids
(VLCFAs) and their derivatives. Primary alcohols are the dominant wax components
throughout leaf development of Brachypodium distachyon (Brachypodium). However,
the genes involved in primary alcohol biosynthesis have not been investigated and
their exact biological function remains unclear in Brachypodium to date. Here, we
monitored the leaf wax profile and crystal morphology during Brachypodium leaf
morphogenesis, and isolated three Brachypodium fatty acyl-CoA reductase (FAR)
genes, named BdFAR1, BdFAR2 and BdFAR3, then analyzed their biochemical
activities, substrate specificities, expression patterns, subcellular
localization and stress induction. Transgenic expression of BdFAR genes in yeast
(Saccharomyces cerevisiae), tomato (Solanum lycopersicum), Arabidopsis
(Arabidopsis thaliana) and Brachypodium increased the production of primary
alcohols. The three BdFAR genes were preferentially expressed in Brachypodium
aerial tissues, consistent with known sites of wax primary alcohol deposition,
and localized in the endoplasmic reticulum (ER) in Arabidopsis protoplasts.
Finally, expression of the BdFAR genes was induced by drought, cold and ABA
treatments, and drought stress significantly increased cuticular wax accumulation
in Brachypodium. Taken together, these results indicate that the three BdFAR
genes encode active FARs involved in the biosynthesis of Brachypodium wax primary
alcohols and respond to abiotic stresses.
PMID- 29329460
TI - Survey of Parasitic Bacteria in Bat Bugs, Colorado.
AB - Bat bugs (Cimex adjunctus Barber) (Hemiptera: Cimicidae) collected from big brown
bats (Eptesicus fuscus Palisot de Beauvoir) in Colorado, United States were
assessed for the presence of Bartonella, Brucella, and Yersinia spp. using
molecular techniques. No evidence of Brucella or Yersinia infection was found in
the 55 specimens collected; however, 4/55 (7.3%) of the specimens were positive
for Bartonella DNA. Multi-locus characterization of Bartonella DNA shows that
sequences in bat bugs are phylogenetically related to other Bartonella isolates
and sequences from European bats.
PMID- 29329461
TI - High heritability of adolescent sleep-wake behavior on free, but not school days:
a long-term twin study.
AB - Adolescence development is characterized by significant changes in sleep biology.
Despite an overall decline in sleep duration and a delay in bedtime, significant
interindividual variation in sleep has been reported. The aim of the current
study was to examine genetic and environmental influences on sleep in adolescence
using long-term (6 month) actigraphy measurements, differentiating between school
and free days. Sixteen monozygotic (n = 32) and 10 dizygotic (n = 20) twin pairs
(mean age 12.8 +/- 1.0 years; 25 females) participated in the study. Structural
equation modeling was used to compute genetic, shared environmental and unique
environmental contributors to sleep behavior. We found significantly more genetic
influence on sleep timing (sleep midpoint; school: 14%, free: 90%) and duration
(school: 15%; free: 68%) on free compared with school days. On the other hand,
the genetic influence on measures of sleep quality (sleep efficiency and sleep
onset latency) was high (>60%) and less dependent on the day of measurement. Only
wake after sleep onset (WASO) exhibited a strong shared environmental influence
(> 52%) on both school and free days, suggesting that behavioral/environmental
interventions may help reduce WASO. In addition, self-reported chronotype was
also highly genetically influenced (75%). Disrupted, ill-timed, and insufficient
sleep in adolescence is associated with poor mental and physical health outcomes.
Our findings of a strong genetic contribution to sleep in adolescence suggest
that sleep may mark a genetic vulnerability to poor outcomes.
PMID- 29329462
TI - Silibinin from Silybum marianum Stimulates Embryonic Stem Cell Vascular
Differentiation via the STAT3/PI3-K/AKT Axis and Nitric Oxide.
AB - Silibinin, the bioactive compound of milk thistle (Silybum marianum), exerts
tissue protective and regenerative effects that may include stem cell
differentiation toward vascular cells. The purpose of the present study was to
investigate whether silibinin stimulates blood vessel formation from mouse
embryonic stem (ES) cells and to unravel the underlying signaling cascade.
Vascular branching points were assessed by confocal laser scanning microscopy and
computer-assisted image analysis of CD31-positive cell structures. Protein
expression of vascular markers and activation of protein kinases were determined
by western blot. Nitric oxide (NO) generation was investigated by use of the
fluorescent dye 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate.
Silibinin dose-dependently increased CD31-positive vascular branching points in
embryoid bodies cultivated from ES cells. This was paralleled by increase of
protein expression levels for the endothelial-specific markers vascular
endothelial cadherin (VE-cadherin), vascular endothelial growth factor receptor
2, and hypoxia-inducible factor-1alpha. Moreover, silibinin increased activation
of endothelial nitric oxide synthase (eNOS), which boosted generation of NO in
embryoid bodies and enhanced phosphorylation of signal transducer and activator
of transcription 3 (STAT3) as well as phosphoinositide 3-kinase (PI3-K) and AKT.
Vasculogenesis, VE-cadherin expression, STAT3 and AKT phosphorylation, NO
generation, and eNOS phosphorylation were inhibited by the small molecule STAT3
inhibitor Stattic, AKT inhibitor VIII, the PI3-K inhibitor LY294002, or the NOS
inhibitor Nomega-Nitro-L-arginine methyl ester hydrochloride. In conclusion, our
findings indicate that silibinin induces vasculogenesis of ES cells via
activation of STAT3, PI3-K, and AKT, which regulate NO generation by eNOS.
PMID- 29329464
TI - [The Use of Social Networks and Physical Activity Patterns of Adolescents in
Obesity Therapy - A Sociodemographic Stratified Analysis].
AB - The improvement of existing obesity treatment for children and adolescents
requires knowledge about social and personal conditions, individual needs, and
life style. From particular importance are information about physical activity
and media use, in order to target and adjust content and methods of therapy
interventions. In 2013, 510 adolescents aged 11 to 17 years participated in a
survey on above named factors. Physical activities were conducted with friends
(64%) and in sport clubs (43%). Girls (OR 0.55) and children of unemployed
parents (OR 0.28) had reduced chances to participate in sports clubs. Through
social media social networks, primarily Facebook, were widely used. The use of
the network functions differed among socio-demographic groups. Participants who
completed obesity treatments expressed their desire to share their experience
with other treatment participants (79%) and with the therapy team (37%). The
results indicate the need for individualised treatment approaches.
PMID- 29329463
TI - Ginsenoside Rh1: A Systematic Review of Its Pharmacological Properties.
AB - Ginsenoside Rh1 is one of major bioactive compounds extracted from red ginseng,
which has been increasingly used for enhancing cognition and physical health
worldwide. The objective of this study was to review the pharmacological effects
of ginsenoside Rh1 in a systematic manner. We performed searches on eight
electronic databases including MEDLINE (Pubmed), Scopus, Google Scholar, POPLINE,
Global Health Library, Virtual Health Library, the System for Information on Grey
Literature in Europe, and the New York Academy of Medicine Grey Literature Report
to select the original research publications reporting the biological and
pharmacological effects of ginsenoside Rh1 from in vitro and in vivo studies
regardless of publication language and study design. Upon applying the inclusion
and exclusion criteria, we included a total of 57 studies for our systemic
review. Ginsenoside Rh1 exhibited the potent characteristics of anti
inflammatory, antioxidant, immunomodulatory effects, and positive effects on the
nervous system. The cytotoxic effects of ginsenoside Rh1 were dependent on
different types of cell lines. Other pharmacological effects including
estrogenic, enzymatic, anti-microorganism activities, and cardiovascular effects
have been mentioned, but the results were considerably diverged. A higher quality
of evidence on clinical trial studies is highly recommended to confirm the
consistent efficacy of ginsenoside Rh1.
PMID- 29329466
TI - Association Between Body Weight Change Before and After Delivery and Development
of Nonmetabolic Syndrome: A Prospective Study.
AB - The aim of the work was to investigate the association between body weight change
before and after delivery and development of nonmetabolic syndrome in Chinese
females aged >=40 years. We selected 789 participants without metabolic syndrome
randomly from a baseline survey performed in Luzhou, China in 2011. We took the
group with decreasing or no increasing body mass index difference during a
pregnancy as "R-Body Mass Index 1" (n=286) and divided the group with increasing
body mass index difference during a pregnancy into "R-Body Mass Index 2" (n=254)
and "R-Body Mass Index 3" (n=249) based upon P50. All study participants were
followed up every year, and a questionnaire, physical examination, and
biochemical detection were administered after 3 years. Of 789 participants, 82
nonmetabolic syndrome women developed metabolic syndrome during 3-year follow-up.
The morbidity of metabolic syndrome in the R-BMI1, R-BMI2, and R-BMI3 groups was
5.2%, 11.8%, and 14.9%, respectively. Compared to the R-BMI1 group, the relative
risk for R-BMI2 was 1.92 (95% confidence interval: 1.03-3.58, p=0.040) and for R
BMI3 was 2.20 (95% confidence interval: 1.20-4.03, p=0.011). After adjusting for
age, BMI, WHR, baseline blood glucose, HbA1c, TG, HDL-C, SBP, DBP, age of
menarche and menopause, and delivery times, the relative risks were similar to
the unadjusted relative risks. In conclusion, body weight change after delivery
was associated with metabolic syndrome: the higher the weight gain, the higher
the risk of metabolic syndrome.
PMID- 29329468
TI - Closure of an Intraoperatively Enlarged Macular Hole by Revision Surgery with
Free ILM Flaps.
PMID- 29329467
TI - Low Aromatase Activity and Estradiol/Sex Hormone Binding Globulin Ratio are
Associated with Total Hip Bone Mineral Density and the Presence of Osteoporosis:
A Study in Chinese Postmenopausal Women.
AB - Several groups have reported the important role of estradiol (E2) and
testosterone (T) in postmenopausal osteoporosis (PMOP). Because aromatase
catalyzes the conversion of T to E2, the purpose of this study was to determine
the influence of aromatase activity on the bone mineral density (BMD) in
postmenopausal women. A total of 344 postmenopausal women were selected for this
study. Serum E2, T, sex hormone-binding globulin (SHBG), calcium (Ca), alkaline
phosphatase (ALP), C-terminal telopeptide of type I collagen (CTX), and
procollagen type I amino-terminal propeptide (PINP) were examined. The E2/T was
positively associated with total hip BMD and PINP (p<0.05). When E2/T was divided
into quartiles, participants in lower quartiles of E2/T were likely to have
higher PINP and lower BMD (p<0.05). The prevalence of osteoporosis significantly
increased as E2/T ratio decreased. The receiver operating characteristic (ROC)
curves were constructed for serum E2, free E2 index (FEI), and E2/T, to assess
their diagnostic accuracy in PMOP. The overall area under the curve (AUC) were
0.83 (95% CI=0.77-0.88) for E2, 0.87 (95% CI=0.82-0.92) for FEI, and 0.89 (95%
CI=0.85-0.94), respectively. In conclusion, the study suggests that in
postmenopausal women, aromatase activity could be an important determinant of
skeletal health. The women with lower aromatase activity may have greater
likelihood of PMOP and the E2/T was expected to be a valuable indicator for the
prediction of PMOP and to monitor the process of osteoporosis.
PMID- 29329469
TI - Pigment Dispersion Syndrome Mimicking Congenital Horner Syndrome.
PMID- 29329470
TI - [The Epidemiology of Pressure Ulcer in Germany: Systematic Review].
AB - BACKROUND: Pressure ulcers are considered as indicators of the quality of care.
The aim of this study was to provide a systematic review of the incidence and
prevalence of pressure ulcers in Germany between 2010 and 2015. METHODS: The
databases PubMed, CINAHL, DIMDI, Web of Science, LIVIVO, Google, Google Scholar,
as well as the publishers Springer and the Thieme were searched until the end of
February 2016. The extracted data were monitored by two reviewers. A risk of bias
assessment was conducted. RESULTS: 219 epidemiologic figures were found in 67
studies and documents. Most data were identified for the hospital setting. The
majority of figures in long-term care was based on primary research. Considering
sources of high methodological quality, prevalence in long-term care varied
between 2% and 5% and between 2% to 4% in hospitals (category 2 and above).
Routine data collections showed heterogeneous results from the hospital settings
with prevalence from 0.07% to 4.37%. No incidence figures and no routine data
collections were identified for ambulatory settings. Prevalence varied between 2
and 4% (including category 1). CONCLUSION: Review results indicate that pressure
ulcers are frequent within all health care settings in Germany. Disregarding
methodological limitations, pressure ulcer prevalence is between 2% and 5% in
long-term care patients. Due to the heterogeneity of the available data,
generalizable statements are not possible for the hospital settings. Pressure
ulcer prevalence is most likely at least 2%. Results indicate that pressure ulcer
preventive measures need to be improved in Germany.
PMID- 29329471
TI - Diagnosing Meniscal Pathology and Understanding How to Evaluate a Postoperative
Meniscus Based on the Operative Procedure.
AB - Magnetic resonance imaging (MRI) represents the preferred noninvasive imaging
technique to diagnose meniscal pathology in the pre- and postoperative setting.
Furthermore, characterization of meniscal tissue MR properties has been possible
by the development of advanced MRI techniques. Suspected meniscal tears are a
frequent indication for MRI and the International Society of Arthroscopy, Knee
Surgery and Orthopaedic Sports Medicine (ISAKOS) classification system has been
developed to facilitate accurate and uniform reporting of such meniscal tears.
Partial meniscectomy and meniscal suture repair are among the commonly performed
procedures and several signs have been described to detect postoperative
recurrent tears on MRI. Other techniques that have proven useful for meniscal
assessment are ultrasound (US) and computed tomography (CT) arthrography. In
recent years, US is being increasingly used in the selective assessment of some
meniscal pathology such as tears, parameniscal cysts and meniscal extrusion as it
is a relatively inexpensive, accessible, and safe technique. CT arthrography has
been advocated as an acceptable alternative in patients with contraindications
for MRI, with comparable diagnostic performance.
PMID- 29329473
TI - Intrabiliary argon plasma coagulation hemostasis by direct cholangioscopy for a
tricky post-ERCP bleeding.
PMID- 29329472
TI - Impact of Thrombus Sidedness on Presentation and Outcomes of Patients with
Proximal Lower Extremity Deep Vein Thrombosis.
AB - Small studies have suggested differences in demographics and outcomes between
left- and right-sided deep vein thrombosis (DVT), and also unilateral versus
bilateral DVT. We investigated the clinical presentation and outcomes of patients
with DVT based on thrombus sidedness. The authors used the data from the Registro
Informatizado Enfermedad TromboEmbolica (RIETE) database (2001-2016) to identify
patients with symptomatic proximal lower-extremity DVT. Main outcomes included
cumulative 90-day symptomatic pulmonary embolism (PE) and 1-year mortality.
Overall, 30,445 patients were included. The majority of DVTs occurred in the left
leg (16,421 left-sided, 12,643 right-sided, and 1,390 bilateral; p < 0.001 for
chi-squared test comparing all three groups). Comorbidities were relatively
similar in those with left-sided and right-sided DVT. Compared with those with
left-sided DVT, patients with right-sided DVT had higher relative frequency of PE
(26% versus 23%, p < 0.001) and 1-year mortality (odds ratio [OR]: 1.08; 95%
confidence interval [CI]: 1.00-1.18). This difference in mortality did not
persist after multivariable adjustment (OR: 1.01; 95% CI: 0.93-1.1). Patients
with bilateral DVT had a greater burden of comorbidities such as heart failure,
and recent surgery compared with those with unilateral DVT (p < 0.001), and
higher relative frequency of PE (48%), and 1-year mortality (24.1%). Worse
outcomes in patients with bilateral DVT were attenuated but persisted after
multivariable adjustment for demographics and risk factors (OR: 1.64; 95% CI:
1.43-1.87). Patients with bilateral DVT had worse outcomes during and after
discontinuation of anticoagulation. There is a left-sided preponderance for
proximal lower-extremity DVT. Compared with those with left-sided DVT, patients
with right-sided DVT have slightly higher rates of PE. Bilateral DVT is
associated with markedly worse short-term and 1-year outcomes.
PMID- 29329474
TI - Immediate retrieval of a maldeployed lumen-apposing metal stent from a walled-off
cavity.
PMID- 29329476
TI - Pay attention to a "window-blind" appearance of the distal rectal muscle layer
during endoscopic submucosal dissection.
PMID- 29329475
TI - Endoscopic ultrasound-guided sclerosant injection and coil embolization of
bleeding gastric varices.
PMID- 29329477
TI - Colorectal endoscopic submucosal dissection using the "dental floss with rubber
band method".
PMID- 29329478
TI - Migrated endoclip removal after cholecystectomy under digital single-operator
cholangioscopy guidance.
PMID- 29329479
TI - Individual endoscopic management of anastomotic insufficiency after esophagectomy
for esophageal squamous cell carcinoma and creation of a neostomach.
PMID- 29329480
TI - Direct endoscopy and diagnosis of adenocarcinoma following metal stent-based
drainage of a pancreatic cyst.
PMID- 29329481
TI - Antibiotics Development and the Emergence of Resistance: Clinical Pharmacology to
the Rescue.
PMID- 29329483
TI - Recognizing elevated blood pressure in pediatrics: the value of repeated
measures.
PMID- 29329482
TI - Pharmacokinetics of Rolapitant in Patients With Mild to Moderate Hepatic
Impairment.
AB - Rolapitant is a selective and long-acting neurokinin-1 receptor antagonist
approved in an oral formulation in combination with other antiemetic agents for
the prevention of delayed chemotherapy-induced nausea and vomiting in adults.
This was a phase 1 open-label, parallel-group pharmacokinetic and safety study of
a single oral dose of 180 mg of rolapitant and its major active metabolite, M19,
in subjects with mild and moderate hepatic impairment compared with healthy
matched controls. Pharmacokinetics were assessed by a mixed-model analysis of
variance of log-transformed values for maximum observed plasma concentration
(Cmax ), observed time at Cmax (tmax ), area under the plasma concentration-time
curve (AUC) from time 0 to the time of the last quantifiable concentration (AUC0
t ), and AUC from time 0 to 120 hours (AUC0-120 ), with hepatic group as a fixed
effect. Mean rolapitant Cmax , AUC0-t , and AUC0-120 were similar in the mild
hepatic impairment and healthy control groups. In subjects with moderate hepatic
impairment, AUC0-t was similar and Cmax was 25% lower than in healthy controls.
Mean M19 Cmax and AUC0-t were similar in the mild hepatic impairment group and
healthy controls, but <20% lower in those with moderate hepatic impairment versus
healthy controls. Fraction of unbound rolapitant was comparable in all groups for
rolapitant and M19. Rolapitant was well tolerated in all groups, without serious
adverse events. Pharmacokinetic differences between healthy subjects and those
with mild or moderate hepatic impairment are unlikely to pose a safety risk and
do not warrant predefined dosage adjustment in the presence of hepatic
impairment.
PMID- 29329484
TI - Effects of Teriparatide Compared with Risedronate on the Risk of Fractures in
Subgroups of Postmenopausal Women with Severe Osteoporosis: The VERO Trial.
AB - The 2-year, randomized, double-blind, active-controlled fracture endpoint VERO
study included postmenopausal women with established osteoporosis, who had at
least 2 moderate or 1 severe baseline vertebral fractures (VFx), and bone mineral
density (BMD) T-score <=-1.5. Patients were treated with either s.c. daily
teriparatide 20 MUg or oral weekly risedronate 35 mg. As previously reported, the
risk of new VFx and clinical fractures (a composite of clinical VFx and
nonvertebral fragility fractures [NVFFx]) was statistically significantly reduced
with teriparatide compared with risedronate. Here we present the prospectively
planned subgroup analyses of fracture data across subgroups, which were
predefined by the following baseline characteristics: age, number and severity of
prevalent VFx, prevalent nonvertebral fractures (NVFx), glucocorticoid use, prior
osteoporosis drugs, recent bisphosphonate use, clinical VFx in the year before
study entry, and baseline BMD. Heterogeneity of the treatment effect on the
primary endpoint (new VFx), and the four key secondary endpoints (including
clinical fractures and NVFFx) were investigated by logistic and Cox proportional
hazards regression models. A total of 1360 women were randomized and treated (680
per group). Mean age was 72.1 years, mean (SD) number of prevalent VFx was 2.7
(2.1), 55.4% had a BMD T-score <-2.5, 36.5% had a recent clinical VFx, 28.3% had
a prior major NVFx, 43.2% were osteoporosis drug-naive, 39.3% were recent
bisphosphonate users, and 9.3% were taking glucocorticoids at a prednisone
equivalent dose of >5 mg/d. For most fracture endpoints, the risk reduction of
teriparatide versus risedronate did not significantly differ in any of the
subgroups analyzed (treatment-by-subgroup interaction p > 0.1), with most
subgroups mirroring results from the total study population. In conclusion, in
postmenopausal women with severe osteoporosis, the antifracture efficacy of
teriparatide compared with risedronate was consistent in a wide range of patient
settings, including treatment-naive and previously treated patients. (c) 2018 The
Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
PMID- 29329485
TI - Photo-Initiated Reduction of CO2 by H2 on Silica Surface.
AB - The reduction of CO2 is a promising route to produce valuable chemicals or fuels
and create C-neutral resource cycles. Many different approaches to CO2 reduction
have been investigated, but the ability of vacuum UV (VUV) irradiation to cleave
C-O bonds has remained largely unexplored for use in processes that convert CO2
into useful products. Compared with other photo-driven CO2 conversion processes,
VUV-initiated CO2 reduction can achieve much greater conversion under common
photochemical reaction conditions when H2 and non-reducible oxides are present.
Infrared spectroscopy provides evidence for a chain reaction initiated by VUV
induced CO2 splitting, which is enhanced in the presence of H2 and silica. When
the reaction is carried out in the presence of silica or alumina surfaces, CO
yields are increased and CH4 is formed as the only other detected product. CH4
production is not promoted by traditional photocatalysts such as TiO2 under these
conditions. Assuming improvements in lamp and reactor efficiencies with scale up,
or coupling with other available CO/CO2 hydrogenation techniques, these results
reveal a potential, simple strategy by which CO2 could be valorized.
PMID- 29329487
TI - A History of Pivotal Advances in Clinical Research into Bone and Mineral
Diseases.
PMID- 29329486
TI - Cost effectiveness of guided Internet-based interventions for depression in
comparison with control conditions: An individual-participant data meta-analysis.
AB - BACKGROUND: There is limited evidence on the cost effectiveness of Internet-based
treatments for depression. The aim was to evaluate the cost effectiveness of
guided Internet-based interventions for depression compared to controls. METHODS:
Individual-participant data from five randomized controlled trials (RCT),
including 1,426 participants, were combined. Cost-effectiveness analyses were
conducted at 8 weeks, 6 months, and 12 months follow-up. RESULTS: The guided
Internet-based interventions were more costly than the controls, but not
statistically significant (12 months mean difference = ?406, 95% CI: - 611 to
1,444). The mean differences in clinical effects were not statistically
significant (12 months mean difference = 1.75, 95% CI: - .09 to 3.60 in Center
for Epidemiologic Studies Depression Scale [CES-D] score, .06, 95% CI: - .02 to
.13 in response rate, and .00, 95% CI: - .03 to .03 in quality-adjusted life
years [QALYs]). Cost-effectiveness acceptability curves indicated that high
investments are needed to reach an acceptable probability that the intervention
is cost effective compared to control for CES-D and response to treatment (e.g.,
at 12-month follow-up the probability of being cost effective was .95 at a
ceiling ratio of 2,000 ?/point of improvement in CES-D score). For QALYs, the
intervention's probability of being cost effective compared to control was low at
the commonly accepted willingness-to-pay threshold (e.g., at 12-month follow-up
the probability was .29 and. 31 at a ceiling ratio of 24,000 and 35,000 ?/QALY,
respectively). CONCLUSIONS: Based on the present findings, guided Internet-based
interventions for depression are not considered cost effective compared to
controls. However, only a minority of RCTs investigating the clinical
effectiveness of guided Internet-based interventions also assessed cost
effectiveness and were included in this individual-participant data meta
analysis.
PMID- 29329488
TI - Genetic and Molecular Insights Into Genotype-Phenotype Relationships in
Osteopathia Striata With Cranial Sclerosis (OSCS) Through the Analysis of Novel
Mouse Wtx Mutant Alleles.
AB - The X-linked WTX/AMER1 protein constitutes an important component of the beta
catenin destruction complex that can both enhance and suppress canonical beta
catenin signaling. Somatic mutations in WTX/AMER1 have been found in a proportion
of the pediatric kidney cancer Wilms' tumor. By contrast, germline mutations
cause the severe sclerosing bone dysplasia osteopathia striata congenita with
cranial sclerosis (OSCS), a condition usually associated with fetal or perinatal
lethality in male patients. Here we address the developmental and molecular
function of WTX by generating two novel mouse alleles. We show that in addition
to the previously reported skeletal abnormalities, loss of Wtx causes severe
midline fusion defects including cleft palate and ectopic synostosis at the base
of the skull. By contrast, deletion of the C-terminal part of the protein results
in only mild developmental abnormalities permitting survival beyond birth. Adult
analysis, however, revealed skeletal defects including changed skull morphology
and an increased whole-body bone density, resembling a subgroup of male patients
carrying a milder, survivable phenotype. Molecular analysis in vitro showed that
while beta-catenin fails to co-immunoprecipitate with the truncated protein,
partial recruitment appears to be achieved in an indirect manner using AXIN/AXIN2
as a molecular bridge. Taken together our analysis provides a novel model for WTX
caused bone diseases and explains on the molecular level how truncation mutations
in this gene may retain some of WTX-protein functions. (c) 2018 American Society
for Bone and Mineral Research.
PMID- 29329489
TI - Mycophenolic Acid and Its Metabolites in Kidney Transplant Recipients: A
Semimechanistic Enterohepatic Circulation Model to Improve Estimating Exposure.
AB - Mycophenolic acid (MPA) is an approved immunosuppressive agent widely prescribed
to prevent rejection after kidney transplantation. Wide between-subject
variability (BSV) in MPA exposure exists which in part may be due to variability
in enterohepatic recirculation (EHC). Several modeling strategies were developed
to evaluate EHC as part of MPA pharmacokinetics, however mechanistic
representation of EHC is limited. These models have not provided a satisfactory
representation of the physiology of EHC in their modeling assumptions. The aim of
this study was i) to develop an integrated model of MPA (total and unbound) and
its metabolites (MPAG and acyl-MPAG) in kidney recipients, where this model
provides a more physiological representation of EHC process, and ii) to evaluate
the effect of donor and recipient clinical covariates and genotypes on MPA
disposition. A five-compartment model with first-order input into an unbound MPA
compartment connected to the MPAG, acyl-MPAG, and gallbladder compartment best
fit the data. To represent the EHC process, the model was built based on the
physiological concepts related to the hepatobiliary system and the gallbladder
filling and emptying processes. The effect of cyclosporine versus tacrolimus on
clearance of unbound MPA was included in the base model. Covariate analysis
showed creatinine clearance to be significant on oral clearance of unbound MPA.
The hepatic nuclear factor 1 alpha (HNF1A) genetic single nucleotide polymorphism
(SNP) (rs2393791) in the recipient significantly affected the fraction of
enterohepatically-circulated drug. Oral clearance of MPAG was affected by
recipient IMPDH1 SNP (rs2288553), diabetes at the time of transplant, and donor
sex.
PMID- 29329490
TI - Nematode eggs observed in cytology of cerebrospinal fluid diagnostic for
intramedullary Spirocerca lupi spinal cord migration.
AB - Spinal spirocercosis due to aberrant Spirocerca lupi nematode migration is an
emerging etiology for acute myelitis in dogs in Israel, causing severe, mostly
nonsymmetrical hind limb paresis or paralysis, and sometimes tetraparesis or
tetraparalysis. So far, incidental identification of parasites during spinal
surgery or at necropsy provides the only definite diagnosis, while antemortem
diagnosis of this condition has been uncertain. Specifically, antemortem
diagnosis is based on the typical clinical presentation of acute, progressive,
asymmetrical hind limb paresis or paralysis, with moderate to severe eosinophilic
to mixed cerebrospinal fluid (CSF) pleocytosis and increased CSF protein
concentration. Exclusion of other differential diagnoses also requires using
spinal cord imaging. In this novel report, we document a case of an intradural
spinal spirocercosis in a dog, diagnosed antemortem, by detecting S lupi eggs in
the CSF, and subsequent treatment, resulting in the resolution of the clinical
signs.
PMID- 29329492
TI - Failure to confirm high blood pressures in pediatric care-quantifying the risks
of misclassification.
AB - Pediatric practice guidelines call for repeating an elevated office blood
pressure (BP) at the same visit, but there are few data available to support this
recommendation. We compared the visit results in children aged 3 to 17 years with
a BP reading >=95th percentile (n = 186 732) based on the initial BP and the mean
of two BP readings, using electronic medical records from 2012-2015. Failure to
repeat an initial BP reading >=95th percentile would lead to a false
"hypertensive" visit result in 54.1% of children who would require follow-up
visits. After an initial visit result indicating hypertension, hypertension stage
I or stage II was sustained in 2.3% and 11.3% of youth during their next visits,
respectively. In conclusion, only approximately half of the pediatric patients
would be correctly classified based on their initial BP. The recommendation to
repeat high BP during the same visit needs to be emphasized because it saves
unnecessary follow-up visits.
PMID- 29329493
TI - A Randomized Double-Blind Controlled Trial of Intravenous Meloxicam in the
Treatment of Pain Following Dental Impaction Surgery.
AB - : This randomized, controlled phase 2 study was conducted to evaluate the
analgesic efficacy, safety, and tolerability of single intravenous (IV) doses of
15 mg, 30 mg, and 60 mg meloxicam compared with oral ibuprofen 400 mg and placebo
after dental impaction surgery. The primary efficacy end point was the sum of
time-weighted pain intensity differences for 0-24 hours postdose. Among 230
evaluable subjects, meloxicam IV 60 mg produced the greatest reduction in pain,
followed by the 30-mg and 15-mg doses. Statistically significant differences in
summed pain intensity differences over 24 hours were demonstrated for each active
treatment group vs placebo (favoring active treatment) and for meloxicam IV 30 mg
and 60 mg vs ibuprofen 400 mg (favoring meloxicam IV). Moreover, there was a
statistically significant dose response for meloxicam IV 15 mg to 60 mg. The
onset of action for meloxicam IV was rapid and sustained; significant differences
in pain intensity differences were detected as early as 10 minutes postdose and
lasted through the 24-hour postdose period. Subjects in the meloxicam IV groups
were more likely than placebo recipients to achieve perceptible and meaningful
pain relief and were less likely to use rescue medication. Patient-reported
global evaluation showed that meloxicam IV 60 mg had the highest rating. There
were no deaths, serious adverse events, or discontinuations due to adverse
events. The incidence of subjects with >=1 treatment-emergent adverse event was
greatest in the placebo group, followed by the groups that received ibuprofen,
meloxicam IV 15 mg, 30 mg, and 60 mg. Nausea was the most commonly reported
treatment-emergent adverse event. CLINICAL TRIAL REGISTRATION NUMBER:
NCT00945763.
PMID- 29329494
TI - Contraceptive Use over Five Years After Receipt Or Denial of Abortion Services.
AB - CONTEXT: Nonuse and inconsistent use of contraceptives contribute to a high
incidence of unintended pregnancy and abortion among U.S. women. Little is known,
however, about how these outcomes shape women's subsequent contraceptive use and
unintended pregnancy risk. METHODS: Contraceptive use was examined among 880
participants in the Turnaway Study, a five-year longitudinal study of women who
sought abortions at 30 U.S. facilities in 2008-2010. Multivariable mixed-effects
logistic and multinomial regression models assessed differences in use by whether
women received the abortion; results were used to calculate predicted percentages
of women using each method. The main groups of interest were 415 women who had an
abortion at a gestation near their facility's limit and 160 who were denied
abortion because they were beyond the limit, and who consequently gave birth.
RESULTS: During each of the approximately five years of follow-up, the predicted
percentage using any contraceptive method was 86% among women who had the
abortion and 81% among those denied it. Over the entire period, the former women
were more likely than the latter to use any method (odds ratio, 1.8). However,
they were less likely to rely on female sterilization, rather than no method
(risk ratio, 0.5), and more likely to use barrier methods (1.7) or short-acting
reversible contraceptives (2.6). CONCLUSION: Women's elevated risk of unintended
pregnancy after abortion is likely due at least partly to reliance on methods
with relatively low effectiveness. Factors affecting contraceptive access
postabortion, as well as individual characteristics such as fecundability,
require research attention.
PMID- 29329495
TI - Organometallic-Mediated Radical Polymerization of Vinylidene Fluoride.
AB - An unprecedented level of control for the radical polymerization of vinylidene
fluoride (VDF), yielding well-defined PVDF (at least up to 14 500 g mol-1 ) with
low dispersity (<=1.32), was achieved using organometallic-mediated radical
polymerization (OMRP) with an organocobalt compound as initiator. The high chain
end fidelity was demonstrated by the synthesis of PVDF- and PVAc-containing di
and triblock copolymers. DFT calculations rationalize the efficient reactivation
of both head and tail chain end dormant species.
PMID- 29329496
TI - Positive-Feedback Regulation of Subchondral H-Type Vessel Formation by
Chondrocyte Promotes Osteoarthritis Development in Mice.
AB - Vascular-invasion-mediated interactions between activated articular chondrocytes
and subchondral bone are essential for osteoarthritis (OA) development. Here, we
determined the role of nutrient sensing mechanistic target of rapamycin complex 1
(mTORC1) signaling in the crosstalk across the bone cartilage interface and its
regulatory mechanisms. Then mice with chondrocyte-specific mTORC1 activation
(Tsc1 CKO and Tsc1 CKOER ) or inhibition (Raptor CKOER ) and their littermate
controls were subjected to OA induced by destabilization of the medial meniscus
(DMM) or not. DMM or Tsc1 CKO mice were treated with bevacizumab, a vascular
endothelial growth factor (VEGF)-A antibody that blocks angiogenesis. Articular
cartilage degeneration was evaluated using the Osteoarthritis Research Society
International score. Immunostaining and Western blotting were conducted to detect
H-type vessels and protein levels in mice. Primary chondrocytes from mutant mice
and ADTC5 cells were treated with interleukin-1beta to investigate the role of
chondrocyte mTORC1 in VEGF-A secretion and in vitro vascular formation. Clearly,
H-type vessels were increased in subchondral bone in DMM-induced OA and aged
mice. Cartilage mTORC1 activation stimulated VEGF-A production in articular
chondrocyte and H-type vessel formation in subchondral bone. Chondrocyte mTORC1
promoted OA partially through formation of VEGF-A-stimulated subchondral H-type
vessels. In particular, vascular-derived nutrients activated chondrocyte mTORC1,
and stimulated chondrocyte activation and production of VEGF, resulting in
further angiogenesis in subchondral bone. Thus a positive-feedback regulation of
H-type vessel formation in subchondral bone by articular chondrocyte nutrient
sensing mTORC1 signaling is essential for the pathogenesis and progression of OA.
(c) 2018 American Society for Bone and Mineral Research.
PMID- 29329497
TI - Pharmacokinetic Interactions Between Elbasvir/Grazoprevir and Immunosuppressant
Drugs in Healthy Volunteers.
AB - Elbasvir (EBR)/grazoprevir (GZR) may be coadministered with immunosuppressant
drugs in posttransplant people who are infected with hepatitis C virus. The aim
of the present study was to assess the safety and pharmacokinetic interactions
between EBR and GZR and single doses of cyclosporine, tacrolimus, mycophenolate
mofetil (MMF), and prednisone. This was a 4-part, open-label study in 58 healthy
volunteers. Participants received single doses of cyclosporine 400 mg, tacrolimus
2 mg, MMF 1 g, or prednisone 40 mg alone or in the presence of once-daily EBR 50
mg/GZR 200 mg. Multiple oral doses of EBR + GZR had no significant effect on
cyclosporine. However, in the presence of cyclosporine, the 24-hour area under
the concentration-time curve of GZR was increased by approximately 15-fold
(geometric mean ratio [90%CI] 15.21 [12.83; 18.04]); the concentration of EBR was
increased approximately 2-fold in the presence of cyclosporine. Coadministration
of EBR/GZR and tacrolimus did not affect the pharmacokinetics of EBR or GZR, but
resulted in an increase in tacrolimus AUC (geometric mean ratio [90%CI] 1.43
[1.24; 1.64]). There were no clinically relevant interactions between EBR/GZR and
either MMF or prednisone. Data from the present study indicate that EBR/GZR may
be coadministered in people receiving tacrolimus, MMF, and prednisolone. EBR/GZR
is contraindicated in people receiving cyclosporine because the significantly
higher concentrations of GZR may increase the risk of transaminase elevations.
PMID- 29329498
TI - Treatment outcomes of acute bipolar depressive episode with psychosis.
AB - BACKGROUND: The impact of psychosis on the treatment of bipolar depression is
remarkably understudied. The primary aim of this study was to compare treatment
outcomes of bipolar depressed individuals with and without psychosis. The
secondary aim was to compare the effect of lithium and quetiapine, each with
adjunctive personalized treatments (APTs), in the psychotic subgroup. METHODS: We
assessed participants with DSM-IV bipolar depression included in a comparative
effectiveness study of lithium and quetiapine with APTs (the Bipolar CHOICE
study). Severity was assessed by the Bipolar Inventory of Symptoms Scale (BISS)
and by the Clinical Global Impression Scale-Severity-Bipolar Version (CGI-S-BP).
Mixed models were used to assess the course of symptom change, and Cox regression
survival analysis was used to assess the time to remission. RESULTS: Psychotic
features were present in 10.6% (n = 32) of the depressed participants (n = 303).
Those with psychotic features had higher scores on the BISS before (75.2 +/- 17.6
vs. 54.9 +/- 16.3; P < .001) and after (37.2 +/- 19.7 vs. 26.3 +/- 18.0; P =
.003) 6-month treatment. The CGI-S-BP yielded similar results. Participants with
and without psychosis had similar course of symptom improvement and similar time
to remission. There was no significant difference in the treatment outcomes of
lithium (n = 11) and quetiapine (n = 21) among the psychotic subgroup.
CONCLUSION: Bipolar depressive episodes with psychotic features are more severe,
and compared to nonpsychotic depressions, present a similar course of
improvement. Given the small number of participants presenting psychosis, the
lack of statistically significant difference between lithium- and quetiapine
based treatment of psychotic bipolar depressive episodes needs replication in a
larger sample.
PMID- 29329499
TI - A pilot study of the comparative efficacy of 100 Hz magnetic seizure therapy and
electroconvulsive therapy in persistent depression.
AB - BACKGROUND: Magnetic seizure therapy (MST) is a novel brain stimulation technique
that uses a high-powered transcranial magnetic stimulation device to produce
therapeutic seizures. Preliminary MST studies have found antidepressant effects
in the absence of cognitive side effects but its efficacy compared to
electroconvulsive therapy (ECT) remains unclear. The aim of this study was to
investigate the therapeutic efficacy and cognitive profile of MST compared to
standard right unilateral ECT treatment. METHODS: Thirty-seven patients completed
a course of at least nine ECT or MST treatments in a randomized double-blind
protocol. Assessments of depression severity and cognition were performed before
and after treatment. RESULTS: No difference in the antidepressant effectiveness
between the treatments was seen across any of the clinical outcome measures,
although the overall response rates in both groups were quite low. In regards to
cognition, following MST there were significant improvements in tests of
psychomotor speed, verbal memory, and cognitive inhibition, with no reductions in
cognitive performance. Following ECT there was significant improvement in only
one of the cognitive inhibition tasks. With respect to the between-group
comparisons, the MST group showed a significantly greater improvement on
psychomotor speed than ECT. CONCLUSIONS: MST showed similar efficacy to right
unilateral ECT in patients with treatment-resistant depression without cognitive
side effects but in a sample that was only of sufficient size to demonstrate
relatively large differences in response between the two groups. Future research
should aim to optimize the methods of MST administration and compare its efficacy
to ECT in large randomized controlled trials.
PMID- 29329500
TI - A C=O???Isothiouronium Interaction Dictates Enantiodiscrimination in Acylative
Kinetic Resolutions of Tertiary Heterocyclic Alcohols.
AB - A combination of experimental and computational studies have identified a
C=O???isothiouronium interaction as key to efficient enantiodiscrimination in the
kinetic resolution of tertiary heterocyclic alcohols bearing up to three
potential recognition motifs at the stereogenic tertiary carbinol center. This
discrimination was exploited in the isothiourea-catalyzed acylative kinetic
resolution of tertiary heterocyclic alcohols (38 examples, s factors up to >200).
The reaction proceeds at low catalyst loadings (generally 1 mol %) with either
isobutyric or acetic anhydride as the acylating agent under mild conditions.
PMID- 29329502
TI - Energetic Costs, Precision, and Transport Efficiency of Molecular Motors.
AB - An efficient molecular motor would deliver cargo to the target site at a high
speed and in a punctual manner while consuming a minimal amount of energy.
According to a recently formulated thermodynamic principle, referred to as the
thermodynamic uncertainty relation, the travel distance of a motor and its
variance are, however, constrained by the free energy being consumed. Here we use
the principle underlying the uncertainty relation to quantify the transport
efficiency of molecular motors for varying ATP concentration ([ATP]) and applied
load (f). Our analyses of experimental data find that transport efficiencies of
the motors studied here are semioptimized under the cellular condition. The
efficiency is significantly deteriorated for a kinesin-1 mutant that has a longer
neck-linker, which underscores the importance of molecular structure. It is
remarkable to recognize that, among many possible directions for optimization,
biological motors have evolved to optimize the transport efficiency in
particular.
PMID- 29329503
TI - Chemical imaging of aggressive basal cell carcinoma using time-of-flight
secondary ion mass spectrometry.
AB - A set of basal cell carcinoma samples, removed by Mohs micrographic surgery and
pathologically identified as having an aggressive subtype, have been analyzed
using time-of-flight secondary ion mass spectrometry (SIMS). The SIMS analysis
employed a gas cluster ion beam (GCIB) to increase the sensitivity of the
technique for the detection of intact lipid species. The GCIB also allowed these
intact molecular signals to be maintained while surface contamination and
delocalized chemicals were removed from the upper tissue surface. Distinct mass
spectral signals were detected from different regions of the tissue (epidermis,
dermis, hair follicles, sebaceous glands, scar tissue, and cancerous tissue)
allowing mass spectral pathology to be performed. The cancerous regions of the
tissue showed a particular increase in sphingomyelin signals that were detected
in both positive and negative ion mode along with increased specific
phosphatidylserine and phosphatidylinositol signals observed in negative ion
mode. Samples containing mixed more and less aggressive tumor regions showed
increased phosphatidylcholine lipid content in the less aggressive areas similar
to a punch biopsy sample of a nonaggressive nodular lesion.
PMID- 29329504
TI - Expression of vitamin D receptor in the subsynovial connective tissue in women
with carpal tunnel syndrome.
AB - : Studies suggest that low vitamin D levels are associated with carpal tunnel
syndrome. We aimed to evaluate whether level of vitamin D receptor expression in
the endothelial cells of the subsynovial connective tissue is associated with
clinical features of carpal tunnel syndrome. We obtained the subsynovial
connective tissue from 52 women with carpal tunnel syndrome during surgery and
performed immunohistochemical analysis of vitamin D receptors in the endothelial
cells of the subsynovial connective tissue. We explored correlation of vitamin D
receptor expression with clinical features of carpal tunnel syndrome, such as
age, symptom duration, symptom severity and electrophysiological severity.
Diverse range of vitamin D receptor expression was observed. Vitamin D receptor
expression was independently associated with distal motor latency. This suggests
that vitamin D receptor expression may be associated with disease progression, as
prolonged distal motor latency reflects severity of the disease. Further studies
are necessary to explore the role of vitamin D and vitamin D receptors in
patients with carpal tunnel syndrome. LEVEL OF EVIDENCE: IV.
PMID- 29329501
TI - Sustained plasma hepcidin suppression and iron elevation by Anticalin-derived
hepcidin antagonist in cynomolgus monkey.
AB - BACKGROUND AND PURPOSE: Anaemia of chronic disease (ACD) has been linked to iron
restricted erythropoiesis imposed by high circulating levels of hepcidin, a 25
amino acid hepatocyte-derived peptide that controls systemic iron homeostasis.
Here, we report the engineering of the human lipocalin-derived, small protein
based anticalin PRS-080 hepcidin antagonist with high affinity and selectivity.
EXPERIMENTAL APPROACH: Anticalin- and hepcidin-specific pharmacokinetic
(PK)/pharmacodynamic modelling (PD) was used to design and select the suitable
drug candidate based on t1/2 extension and duration of hepcidin suppression. The
development of a novel free hepcidin assay enabled accurate analysis of bioactive
hepcidin suppression and elucidation of the observed plasma iron levels after PRS
080-PEG30 administration in vivo. KEY RESULTS: PRS-080 had a hepcidin-binding
affinity of 0.07 nM and, after coupling to 30 kD PEG (PRS-080-PEG30), a t1/2 of
43 h in cynomolgus monkeys. Dose-dependent iron mobilization and hepcidin
suppression were observed after a single i.v. dose of PRS-080-PEG30 in cynomolgus
monkeys. Importantly, in these animals, suppression of free hepcidin and
subsequent plasma iron elevation were sustained during repeated s.c. dosing.
After repeated dosing and followed by a treatment-free interval, all iron
parameters returned to pre-dose values. CONCLUSIONS AND IMPLICATIONS: In
conclusion, we developed a dose-dependent and safe approach for the direct
suppression of hepcidin, resulting in prolonged iron mobilization to alleviate
iron-restricted erythropoiesis that can address the root cause of ACD. PRS-080
PEG30 is currently in early clinical development.
PMID- 29329505
TI - Tips to avoid complications related to direct cannulation of the axillary artery.
PMID- 29329506
TI - Response to 'Finding the perfect sclerosant - is it possible?'
PMID- 29329507
TI - Differences in salaries of physician assistants in the USA by race, ethnicity and
sex.
AB - Objectives Data from the Academy of American Physician Assistants have suggested
there are no differences in salaries by race and ethnic group. Our objective was
to compare salaries of physician assistants for different racial and ethnic
groups and sexes using another data source. Methods Data from the American
Community Surveys (2010-2012) to examine pay differentials of physician
assistants. Ordinary least squares regression analysis to compare the salaries of
males and females, and those of racial and ethnic groups. Results The majority of
physician assistants in recent decades have been women. Their salaries are
substantially below those of their male counterparts. The number from racial and
ethnic minorities remains low. American Community Surveys data show salaries to
be lower than that reported by the American Academy of Physician Assistants. The
salaries of Black and Hispanic physician assistants lag significantly behind the
salaries of those who are White. Conclusions American Community Surveys data
suggest that previously published Academy of American Physician Assistants survey
data may have been biased with a low percentage of physician assistants from
racial and ethnic minorities which suggests that the Academy of American
Physician Assistants need to focus on recruiting greater numbers of minorities.
PMID- 29329508
TI - Hospital readmissions and the day of the week.
AB - Objectives Patients discharged from hospitals on a Friday (Friday discharges) are
readmitted sooner (a shorter time-to-emergency-readmission) than those discharged
on any other day of the week. To evaluate the cost-effectiveness of increasing
weekend capacity, the effect estimate of Friday discharge on time-to-emergency
readmission needs to be precise. However, precise effect estimation is
complicated by the confounding effect of differing healthcare-seeking behaviour
and admission practices, and therefore different admission probability, by day of
the week. The objective of this research was to examine how differing admission
probability by day of the week influences the effect of discharge day on time-to
emergency-readmission. Methods We used a Markov model to determine how day of the
week admission probability would theoretically affect the time-to-emergency
readmission for Friday and Wednesday discharges. We tested this in a cohort of
patients who have had a history of respiratory illness, using a Cox proportional
hazards model to fit the time-to-emergency-readmission to any Quebec hospital as
a function of the day of the week of discharge and admission. We fitted another
Cox model with an additional time-varying covariate for the current day of the
week, to model differing admission probabilities by day of the week. Results Our
Markov model showed that if admission probability is lower on the weekends,
Friday discharges will be readmitted later (longer time-to-emergency-readmission)
than Wednesday discharges. Using hospital admission data, we found that Friday
discharges were readmitted slightly earlier than Wednesday discharges (HR: 1.03,
95% CI: (1.02, 1.05)). After adding a time-varying covariate for the current day
of the week, the length of time-to-emergency-readmission for a Friday discharge
increased, but it was still earlier than a Wednesday discharge (HR: 1.04, 95% CI:
(1.01, 1.07)). Conclusions The lower admission probabilities on the weekend
confound the effect of Friday discharge on time-to-emergency-readmission by
increasing the time-to-emergency-readmission. This confounding effect causes an
underestimate of the effect of Friday discharge on time-to-emergency-readmission.
PMID- 29329509
TI - Audit of submissions: July 2016-June 2017.
PMID- 29329510
TI - The predictive value of hunger score on gastric evacuation after oral intake of
carbohydrate solution.
AB - BACKGROUND: Surgical patients are asked to fast for a sufficient duration to
ensure that the amount of residual liquid in the stomach is within the safe
range, thereby reducing the risk of gastric reflux perioperatively. The authors
hypothesized that subjective hunger numerical rating scale (NRS) score could also
help assess the process of gastric emptying and determine the amount of fluid
remaining in the stomach. METHODS: The current study consisted of healthy
volunteers recruited by advertisement and mutual introduction. Participants were
asked to rate their subjective hunger feeling every 30 min after oral
administration of 8 mL/kg carbohydrate nutrient solution that contained 10%
maltodextrin and 2.5% sucrose. Consecutively, the gastric residual fluid was
measured by magnetic resonance imagining (MRI). The Spearman's correlation
coefficient, the ROC curves and the stepwise regression were used to analyze the
predictive value of NRS for the gastric emptying process. RESULTS: The cohort
consisted of 29 healthy volunteers enrolled in this study. The area under ROC
curves estimated by the NRS score for the gastric residual volume of 2 mL/kg, 1
mL/kg, and 0.5 mL/kg were AUC2.0 = 0.78, AUC1.0 = 0.76, and AUC0.5 = 0.72,
respectively. The correlation coefficient between the NRS score and the residual
liquid in the stomach was -0.57 (P < 0.01). The correlation coefficient between
the increase of the NRS score and the decrease of gastric liquid residual volume
was 0.46 (P < 0.01). The standardized estimate of NRS score for the residual
volume was -0.18 (P < 0.01) and the standardized estimate of fasting time was
0.73 (P < 0.01). CONCLUSIONS: The subjective hunger NRS score can not accurately
predict the gastric residual volume, but it can provide a reference for
clinicians to judge the gastric emptying process and it should be used as a
second check after oral intake of clear fluids before surgery according to the
new fasting protocol.
PMID- 29329511
TI - Classifying and characterizing the development of adaptive behavior in a
naturalistic longitudinal study of young children with autism.
AB - BACKGROUND: Adaptive behavior, or the ability to function independently in ones'
environment, is a key phenotypic construct in autism spectrum disorder (ASD). Few
studies of the development of adaptive behavior during preschool to school-age
are available, though existing data demonstrate that the degree of ability and
impairment associated with ASD, and how it manifests over time, is heterogeneous.
Growth mixture models are a statistical technique that can help parse this
heterogeneity in trajectories. METHODS: Data from an accelerated longitudinal
natural history study (n = 105 children with ASD) were subjected to growth
mixture model analysis. Children were assessed up to four times between the ages
of 3 to 7.99 years. RESULTS: The best fitting model comprised two classes of
trajectory on the Adaptive Behavior Composite score of the Vineland Adaptive
Behavior Scale, Second Edition-a low and decreasing trajectory (73% of the
sample) and a moderate and stable class (27%). CONCLUSIONS: These results
partially replicate the classes observed in a previous study of a similarly
characterized sample, suggesting that developmental trajectory may indeed serve
as a phenotype. Further, the ability to predict which trajectory a child is
likely to follow will be useful in planning for clinical trials.
PMID- 29329512
TI - Landscape and rodent community composition are associated with risk of
hemorrhagic fever with renal syndrome in two cities in China, 2006-2013.
AB - BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne
disease caused by hantaviruses. Landscape can influence the risk of hantavirus
infection for humans, mainly through its effect on rodent community composition
and distribution. It is important to understand how landscapes influence
population dynamics for different rodent species and the subsequent effect on
HFRS risk. METHODS: To determine how rodent community composition influenced
human hantavirus infection, we monitored rodent communities in the prefecture
level cities of Loudi and Shaoyang, China, from 2006 to 2013. Land use data were
extracted from satellite images and rodent community diversity was analyzed in 45
trapping sites, in different environments. Potential contact matrices,
determining how rodent community composition influence HFRS infection among
different land use types, were estimated based on rodent community composition
and environment type for geo-located HFRS cases. RESULTS: Apodemus agrarius and
Rattus norvegicus were the predominant species in Loudi and Shaoyang,
respectively. The major risk of HFRS infection was concentrated in areas with
cultivated land and was associated with A. agrarius, R. norvegicus, and Rattus
flavipectus. In urban areas in Shaoyang, Mus musculus was related to risk of
hantavirus infection. CONCLUSIONS: Landscape features and rodent community
dynamics may affect the risk of human hantavirus infection. Results of this study
may be useful for the development of HFRS prevention initiatives that are
customized for regions with different geographical environments.
PMID- 29329513
TI - The behavioural phenotype of Potocki-Lupski syndrome: a cross-syndrome
comparison.
AB - BACKGROUND: Potocki-Lupski syndrome (PTLS) and Smith-Magenis syndrome (SMS) are
related genomic disorders, as duplication 17p11.2 (associated with PTLS) is the
reciprocal recombination product of the SMS microdeletion. While SMS has a
relatively well-delineated behavioural phenotype, the behavioural profile in PTLS
is less well defined, despite purported associations with autism spectrum
disorder (ASD) and the suggestion that some behaviours may be diametric to those
seen in SMS. METHODS: Caregivers of individuals with PTLS (N = 34; M age = 12.43,
SD = 6.78) completed online behavioural questionnaires, including the Challenging
Behaviour Questionnaire (CBQ), the Activity Questionnaire (TAQ), the Repetitive
Behaviour Questionnaire (RBQ), the Mood, Interest and Pleasure Questionnaire
Short Form (MIPQ-S) and the Social Communication Questionnaire (SCQ), which
assesses behaviours associated with ASD. Individuals with PTLS were matched on
age and adaptive functioning to individuals with SMS (N = 31; M age = 13.61, SD =
6.85) and individuals with idiopathic ASD (N = 33; M age = 12.04, SD = 5.85) from
an existing dataset. RESULTS: Individuals with PTLS and SMS were less impaired
than those with idiopathic ASD on the communication and reciprocal social
interaction subscales of the SCQ, but neither syndrome group differed from
idiopathic ASD on the restricted, repetitive and stereotyped behaviours subscale.
On the repetitive behaviour measure, individuals with PTLS and idiopathic ASD
scored higher than individuals with SMS on the compulsive behaviour subscale.
Rates of self-injury and property destruction were significantly lower in PTLS
and idiopathic ASD than in SMS. No between-syndrome differences were found in
relation to overactivity or mood; however, impulsivity was greater in SMS than in
PTLS. CONCLUSIONS: Findings suggest some overlap in the behavioural phenotype of
PTLS and features of ASD symptomatology; however, the overall profile of
behaviours in PTLS appears to be divergent from both idiopathic ASD and SMS.
Relative to idiopathic ASD, PTLS is not characterised by communication or social
interaction deficits. However, restricted and repetitive behaviours were evident
in PTLS, and these may be characterised specifically by compulsive behaviours.
While several behavioural differences were identified between PTLS and SMS, there
was little evidence of diametric behavioural phenotypes, particularly in relation
to social behaviour.
PMID- 29329514
TI - Correction to: Short- and long-term outcomes in infective endocarditis patients:
a systematic review and meta-analysis.
AB - CORRECTION: Unfortunately, after publication of this article [1], it was noticed
that the name of the fifth author was incorrectly displayed as Akshaya Srikanth
Bahagavathula. The correct name is Akshaya Srikanth Bhagavathula and can be seen
in the corrected author list above. The original article has also been updated to
correct this error.
PMID- 29329516
TI - Bilateral giant retinal tears in Osteogenesis Imperfecta.
AB - BACKGROUND: Osteogenesis imperfecta (OI) is a rare primarily autosomal dominant
condition in which the connective tissues of bones, ligaments and sclerae do not
form properly. Typically, mutations in COL1A1 and COL1A2 genes lead to the
defective formation or quantity of type I collagen, the principle matrix in these
tissues. Molecular genetic studies have now elucidated multiple genetic subtypes
of the disorder but little literature exists on the risk of retinal tears and
detachments in OI. CASE PRESENTATION: We report the first case of a child with a
rare recessive type of OI, subtype VIII, resulting from a P3H1 (also known as
LEPRE1) gene mutation presenting with bilateral giant retinal tears and the
surgical challenges encountered in performing retinal detachment repair due to
scleral thinning. The P3H1 gene encodes for prolyl 3-hydroxylase 1 which is
involved in the post-translational modification of not only collagen type I but
also types II and V which when mutated may result in pathological posterior
vitreous detachment (PVD) and giant retinal tear detachments. CONCLUSIONS:
Genetic analyses are increasingly important in such cases and may guide patient
monitoring and potential prophylactic treatment, known to significantly reduce
the probability of giant retinal tear detachments in other high-risk
collagenopathies such as Stickler Syndrome Type I.
PMID- 29329515
TI - Engaging clinicians and patients to assess and improve frailty measurement in
adults with end stage renal disease.
AB - BACKGROUND: The Fried frailty phenotype, a measure of physiologic reserve defined
by 5 components (exhaustion, unintentional weight loss, low physical activity,
slow walking speed, and poor grip strength), is associated with poor outcomes
among ESRD patients. However, these 5 components may not fully capture
physiologic reserve in this population. We aimed to ascertain opinions of ESRD
clinicians and patients about the usefulness of the Fried frailty phenotype and
interventions to improve frailty in ESRD patients, and to identify novel
components to further characterize frailty in ESRD. METHODS: Clinicians who treat
adults with ESRD completed a 2-round Delphi study (n = 41 and n = 36,
respectively; response rate = 87%). ESRD patients completed a survey at
transplant evaluation (n = 460; response rate = 81%). We compared clinician and
patient opinions on the constituent components of frailty. RESULTS: Clinicians
were more likely than patients to say that ESRD makes patients frail (97.6% vs.
60.2%). There was consensus among clinicians that exhaustion, low physical
activity, slow walking speed, and poor grip strength characterize frailty in ESRD
patients; however, 29% of clinicians thought weight loss was not relevant.
Patients were less likely than clinicians to say that the 5 Fried frailty
components were relevant. Clinicians identified 10 new ESRD-specific potential
components including falls (64%), physical decline (61%), and cognitive
impairment (39%). Clinicians (83%) and patients (80%) agreed that intradialytic
foot-peddlers might make ESRD patients less frail. CONCLUSIONS: There was
consensus among clinicians and moderate consensus among patients that frailty is
more common in ESRD. Weight loss was not seen as relevant, but new components
were identified. These findings are first steps in refining the frailty phenotype
and identifying interventions to improve physiologic reserve specific to ESRD
patients.
PMID- 29329517
TI - Genome-wide analyses of direct target genes of four rice NAC-domain transcription
factors involved in drought tolerance.
AB - BACKGROUND: Plant stress responses and mechanisms determining tolerance are
controlled by diverse sets of genes. Transcription factors (TFs) have been
implicated in conferring drought tolerance under drought stress conditions, and
the identification of their target genes can elucidate molecular regulatory
networks that orchestrate tolerance mechanisms. RESULTS: We generated transgenic
rice plants overexpressing the 4 rice TFs, OsNAC5, 6, 9, and 10, under the
control of the root-specific RCc3 promoter. We showed that they were tolerant to
drought stress with reduced loss of grain yield under drought conditions compared
with wild type plants. To understand the molecular mechanisms underlying this
tolerance, we here performed chromatin immunoprecipitation (ChIP)-Seq and RNA-Seq
analyses to identify the direct target genes of the OsNAC proteins using the
RCc3:6MYC-OsNAC expressing roots. A total of 475 binding loci for the 4 OsNAC
proteins were identified by cross-referencing their binding to promoter regions
and the expression levels of the corresponding genes. The binding loci were
distributed among the promoter regions of 391 target genes that were directly up
regulated by one of the OsNAC proteins in four RCc3:6MYC-OsNAC transgenic lines.
Based on gene ontology (GO) analysis, the direct target genes were related to
transmembrane/transporter activity, vesicle, plant hormones, carbohydrate
metabolism, and TFs. The direct targets of each OsNAC range from 4.0-8.7% of the
total number of up-regulated genes found in the RNA-Seq data sets. Thus, each
OsNAC up-regulates a set of direct target genes that alter root system
architecture in the RCc3:OsNAC plants to confer drought tolerance. Our results
provide a valuable resource for functional dissection of the molecular mechanisms
of drought tolerance. CONCLUSIONS: Many of the target genes, including
transmembrane/transporter, vesicle related, auxin/hormone related, carbohydrate
metabolic processes, and transcription factor genes, that are up-regulated by
OsNACs act as the cellular components which would alter the root architectures of
RCc3:OsNACs for drought tolerance.
PMID- 29329518
TI - The use of eculizumab in gemcitabine induced thrombotic microangiopathy.
AB - BACKGROUND: Thrombotic microangiopathy (TMA) secondary to gemcitabine therapy
(GiTMA) is a very rare pathology that carries a poor prognosis, with nearly half
of the cases progressing to end stage renal disease. GiTMA is most commonly
associated with adenocarcinomas, most notably pancreatic cancers. The mainstay of
management is withdrawal of the offending drug and supportive care.
Plasmapheresis has a limited role and hemodialysis may help in the management of
fluid overload secondary to renal failure. Furthermore, a C5 inhibitor,
eculizumab, has been successfully used in the treatment of GiTMA. CASE
PRESENTATION: A 64-year-old Caucasian female with history of pancreatic
adenocarcinoma on gemcitabine chemotherapy presented with signs and symptoms of
fluid overload and was found to have abnormal kidney function. Her BP was 195/110
mmHg, serum creatinine 4.48 mg/dl, hemoglobin 8.2 g/dl, platelets 53 * 103/cmm,
lactate dehydrogenase 540 IU/L, and was found to have schistocytes on blood film.
A diagnosis of TMA secondary to gemcitabine therapy was suspected. Hemodialysis
for volume overload and daily plasmapheresis were initiated. After six days of
plasmapheresis, renal function did not improve. Further work up revealed ADAMTS
13 activity >15%, low C3, and stool culture and Shiga-toxin PCR were negative.
Renal biopsy was consistent with TMA. Gemcitabine was discontinued, but renal
function failed to improve and eculizumab therapy was considered due to suspicion
of aHUS. Serum creatinine >2.26 mg/dl and a platelet count of >/= 30 * 109/L is
highly suggestive of aHUS, while TTP is more likely when creatinine is <2.26
mg/dl and platelet count of <30 * 109/L. She received intravenous eculizumab for
eight months, which resulted in significant improvement of renal function. Other
markers of hemolysis, namely LDH and bilirubin, also rapidly improved following
eculizumab therapy. Plasmapheresis and hemodialysis were discontinued after two
and eight weeks of initiation respectively. CONCLUSION: Chemotherapy induced TMA
is very rare and requires a high index of clinical suspicion for timely
diagnosis. Discontinuation of the offending drug and supportive care is the main
stay of treatment; however, eculizumab has been shown to be beneficial in GiTMA.
Further research is required to validate this approach.
PMID- 29329519
TI - Eikenella corrodens endocarditis and liver abscess in a previously healthy male,
a case report.
AB - BACKGROUND: Eikenella corrodens is one of the HACEK bacteria constituting part of
the normal flora of the oropharynx, however, still an uncommon pathogen. We
report a case of a large Eikenella corrodens liver abscess with simultaneously
endocarditis in a previously healthy male. CASE PRESENTATION: A 49-year-old
Danish man was admitted because of one-month malaise, fever, cough and
unintentional weight loss. On admission there was elevated white blood cell count
and C-reactive protein, as well as affected liver function tests. Initially
pneumonia was suspected, but due to lack of improvement on pneumonia treatment, a
PET-CT scan was performed, which showed a large multiloculated abscess in the
liver. The abscess was drained using ultrasound guidance. Culture demonstrated
Eikenella corrodens. Transesophageal echocardiography revealed aortic
endocarditis. The patient was treated with antibiotics and abscess drainage, on
which he slowly improved. He was discharged after 1.5 months of hospitalisation.
On follow-up 2 months later, the patient was asymptomatic with normalized
biochemistry and ultrasound showed complete regression of the abscess.
CONCLUSIONS: This is the first case of documented Eikenella corrodens concurrent
liver abscess and endocarditis. The case report highlights that Eikenella
corrodens should be considered as a cause of liver abscess. Empirical treatment
of pyogenic liver abscess will most often cover Eikenella corrodens, but the
recommended treatment is a third generation cephalosporin or a fluoroquinolon. A
multiloculated liver abscess may require drainage several times during treatment.
The finding of Eikenella corrodens should elicit an echocardiography to diagnose
endocarditis even in patients without clinical signs of endocarditis.
PMID- 29329520
TI - Effects of primary care clinician beliefs and perceived organizational
facilitators on the delivery of preventive care to individuals with mental
illnesses.
AB - BACKGROUND: Although many studies have documented patient-, clinician-, and
organizational barriers/facilitators of primary care among people with mental
illnesses, few have examined whether these factors predict actual rates of
preventive service use. We assessed whether clinician behaviors, beliefs,
characteristics, and clinician-reported organizational characteristics, predicted
delivery of preventive services in this population. METHODS: Primary care
clinicians (n = 247) at Kaiser Permanente Northwest (KPNW) or community health
centers and safety-net clinics (CHCs), in six states, completed clinician surveys
in 2014. Using electronic health record data, we calculated preventive care-gap
rates for patients with mental illnesses empaneled to survey respondents (n =
37,251). Using separate multi-level regression models for each setting, we tested
whether survey responses predicted preventive service care-gap rates. RESULTS:
After controlling for patient-level characteristics, patients of clinicians who
reported a greater likelihood of providing preventive care to psychiatrically
asymptomatic patients experienced lower care-gap rates (KPNW gamma= - .05, p =
.041; CHCs gamma= - .05, p = .033). In KPNW, patients of female clinicians had
fewer care gaps than patients of male clinicians (gamma= - .07, p = .011). In
CHCs, patients of clinicians who had practiced longer had fewer care gaps (gamma=
- .004, p = .010), as did patients whose clinicians believed that organizational
quality goals facilitate preventive service provision (gamma= - .06, p = .006).
Case manager availability in CHCs was associated with higher care-gap rates
(gamma=.06, p = .028). CONCLUSIONS: Clinicians who report they are likely to
address preventive concerns when their mentally ill patients present without
apparent psychiatric symptoms had patients with fewer care gaps. In CHCs, care
quality goals may facilitate preventive care whereas case managers may not.
PMID- 29329521
TI - Treating C3 glomerulopathy with eculizumab.
AB - BACKGROUND: C3 glomerulopathy (C3G) is a rare, but severe glomerular disease with
grim prognosis. The complex pathogenesis is just unfolding, and involves acquired
as well as inherited dysregulation of the alternative pathway of the complement
cascade. Currently, there is no established therapy. Treatment with the C5
complement inhibitor eculizumab may be a therapeutic option. However, due to
rarity of the disease, parameters predicting treatment response remain largely
unknown. METHODS: Seven patients with C3G (five with C3 glomerulonephritis and
two with dense deposit disease) were treated with eculizumab. Subjects underwent
biopsy before enrollment. The histopathology, clinical data, and response to
eculizumab treatment were analyzed. The key parameters to determine outcome were
changes of serum creatinine and urinary protein over time. RESULTS: After
treatment with eculizumab, four subjects showed significantly improved or stable
renal function and urinary protein. A positive response occurred between 2 weeks
and 6 months after therapy initiation. One subject (with allograft recurrent C3
glomerulonephritis) initially showed a positive response, but relapsed when
eculizumab was discontinued, and did not respond after re-initiation of
treatment. Two subjects showed impaired renal function and increasing urinary
protein despite therapy with eculizumab. CONCLUSIONS: Eculizumab may be a
therapeutic option for a subset of C3G patients. The response to eculizumab is
heterogeneous, and early as well as continuous treatment may be necessary to
prevent disease progression. These findings emphasize the need for studies
identifying genetic and functional complement abnormalities that may help to
guide eculizumab treatment and predict response.
PMID- 29329522
TI - A-GAME: improving the assembly of pooled functional metagenomics sequence data.
AB - BACKGROUND: Expression screening of environmental DNA (eDNA) libraries is a
popular approach for the identification and characterization of novel microbial
enzymes with promising biotechnological properties. In such "functional
metagenomics" experiments, inserts, selected on the basis of activity assays, are
sequenced with high throughput sequencing technologies. Assembly is followed by
gene prediction, annotation and identification of candidate genes that are
subsequently evaluated for biotechnological applications. RESULTS: Here we
present A-GAME (A GAlaxy suite for functional MEtagenomics), a web service
incorporating state of the art tools and workflows for the analysis of eDNA
sequence data. We illustrate the potential of A-GAME workflows using real
functional metagenomics data, showing that they outperform alternative
metagenomics assemblers. Dedicated tools available in A-GAME allow efficient
analysis of pooled libraries and rapid identification of candidate genes,
reducing sequencing costs and saving the need for laborious manual annotation.
CONCLUSION: In conclusion, we believe A-GAME will constitute a valuable resource
for the functional metagenomics community. A-GAME is publicly available at
http://beaconlab.it/agame.
PMID- 29329523
TI - Early commitment of cardiovascular autonomic modulation in Brazilian patients
with congenital generalized lipodystrophy.
AB - BACKGROUND: Metabolic abnormalities in congenital generalized lipodystrophy (CGL)
are associated with microvascular complications. However, the evaluation of
different types of neuropathy in these patients, including the commitment of
cardiovascular autonomic modulation, is scarce. The objective of the present
study was to determine the prevalence of cardiovascular autonomic neuropathy
(CAN) in patients with CGL compared with individuals with type 1 diabetes and
healthy subjects. METHODS: Ten patients with CGL, 20 patients with type 1
diabetes and 20 healthy subjects were included in the study. Controls were paired
1:2 for age, gender, BMI and pubertal stage. Heart rate variability (HRV) was
analyzed using cardiovascular autonomic reflex tests, including postural
hypotension test, Valsalva (VAL), respiratory (E/I) and orthostatic (30/15)
coefficients, and spectral analysis of the HRV, determining very low (VLF), low
(LF) and high (HF) frequencies components. The diagnosis of CAN was defined as
the presence of at least two altered tests. RESULTS: CAN was detected in 40% of
the CGL patients, 5% in type 1 diabetes patients and was absent in healthy
individuals (p < 0.05). We observed a significant reduction in the E/I, VLF, LF
and HF in CGL cases vs. type 1 diabetes and healthy individuals and lower levels
of 30/15 and VAL in CGL vs. healthy individuals. A significant positive
correlation was observed between leptin and 30/15 coefficient (r = 0.396; p =
0.036) after adjusting for insulin resistance and triglycerides. Autonomic
cardiovascular tests were associated with HbA1c, HOMA-IR, triglycerides and
albumin/creatinine ratio in CGL cases. CONCLUSIONS: We observed a high prevalence
of CAN in young patients with CGL, suggesting that insulin resistance,
hypertriglyceridemia and hypoleptinemia, may have been involved in early CAN
development. Additional studies are needed to evaluate the role of leptinemia in
the physiopathogenesis of the condition.
PMID- 29329524
TI - Uncovering the evolutionary history of neo-XY sex chromosomes in the grasshopper
Ronderosia bergii (Orthoptera, Melanoplinae) through satellite DNA analysis.
AB - BACKGROUND: Neo-sex chromosome systems arose independently multiple times in
evolution, presenting the remarkable characteristic of repetitive DNAs
accumulation. Among grasshoppers, occurrence of neo-XY was repeatedly noticed in
Melanoplinae. Here we analyzed the most abundant tandem repeats of R. bergii (2n
= 22, neo-XY?) using deep Illumina sequencing and graph-based clustering in order
to address the neo-sex chromosomes evolution. RESULTS: The analyses revealed ten
families of satDNAs comprising about ~1% of the male genome, which occupied
mainly C-positive regions of autosomes. Regarding the sex chromosomes, satDNAs
were recorded within centromeric or interstitial regions of the neo-X chromosome
and four satDNAs occurred in the neo-Y, two of them being exclusive (Rber248 and
Rber299). Using a combination of probes we uncovered five well-defined
cytological variants for neo-Y, originated by multiple paracentric inversions and
satDNA amplification, besides fragmented neo-Y. These neo-Y variants were
distinct in frequency between embryos and adult males. CONCLUSIONS: The genomic
data together with cytogenetic mapping enabled us to better understand the neo
sex chromosome dynamics in grasshoppers, reinforcing differentiation of neo-X and
neo-Y and revealing the occurrence of multiple additional rearrangements involved
in the neo-Y evolution of R. bergii. We discussed the possible causes that led to
differences in frequency for the neo-Y variants between embryos and adults.
Finally we hypothesize about the role of DNA satellites in R. bergii as well as
putative historical events involved in the evolution of the R. bergii neo-XY.
PMID- 29329525
TI - Reporting of heterogeneity of treatment effect in cohort studies: a review of the
literature.
AB - BACKGROUND: This article corresponds to a literature review and analyze how
heterogeneity of treatment (HTE) is reported and addressed in cohort studies and
to evaluate the use of the different measures to HTE analysis. METHODS:
prospective cohort studies, in English language, measuring the effect of a
treatment (pharmacological, interventional, or other) published among 119 core
clinical journals (defined by the National Library of Medicine) in the last 16
years were selected in the following data source: Medline. One reviewer randomly
sampled journal articles with 1: 1 stratification by journal type: high impact
journals (the New England Journal of Medicine, JAMA, LANCET, Annals of Internal
Medicine, BMJ and Plos Medicine) and low impact journal (the remaining journals)
to identify 150 eligible studies. Two reviewers independently and in duplicate
used standardized piloted forms to screen study reports for eligibility and to
extract data. They also used explicit criteria to determine whether a cohort
study reported HTE analysis. Logistic regression was used to examine the
association of prespecified study characteristics with reporting versus not
reporting of heterogeneity of treatment effect. RESULTS: One hundred fifty cohort
studies were included of which 88 (58%) reported HTE analysis. High impact
journals (Odds Ratio: 3.5, 95% CI: 1.78-7.5; P < 0.001), pharmacological studies
(Odds Ratio: 0.26, 95% CI: 0.13-0.51; P < 0.001) and studies published after 2014
(Odds Ratio: 0.5, 95% CI: 0.25-0.97; P = 0.004) were associated with more
frequent reporting of HTE. 27 (31%) studies which reported HTE used an
interaction test. CONCLUSION: More than half cohort studies report some measure
of heterogeneity of treatment effect. Prospective cohort studies published in
high impact journals, with large sample size, or studying a pharmacological
treatment are associated with more frequent HTE reporting. The source of funding
was not associated with HTE reporting. There is a need for guidelines on how to
perform HTE analyses in cohort studies.
PMID- 29329527
TI - Emotional and cognitive experiences during the time of diagnosis and decision
making following a prenatal diagnosis: a qualitative study of males presented
with congenital heart defect in the fetus carried by their pregnant partner.
AB - BACKGROUND: Expectant fathers consider the second-trimester obstetric ultrasound
examination as an important step towards parenthood, but are ill prepared for a
detection of a fetal anomaly. Inductive research is scarce concerning their
experiences and needs for support. Consequently, the aim of this study was to
explore the emotional and cognitive experiences, during the time of diagnosis and
decision-making, among males presented with congenital heart defect in the fetus
carried by their pregnant partner. METHODS: Twelve expectant fathers were
consecutively recruited through two tertiary referral centers for fetal
cardiology in Sweden, after they had been presented with a prenatal diagnosis of
congenital heart defect in the fetus carried by their pregnant partner. The
respondents were interviewed via telephone, and the interviews were analyzed
using inductive qualitative content analysis. RESULTS: The respondents
experienced an intense emotional shock in connection with detection. However,
they set their own needs aside to attend to the supportive needs of their
pregnant partner, and stressed the importance of an informed joint decision
regarding whether to continue or terminate the pregnancy. When terminating the
pregnancy, they experienced a loss of a wanted child, an emotionally intense
termination procedure, needs of support neglected by professionals, and worries
about the risk of recurrence in future pregnancies. When continuing the
pregnancy, they tried to keep a positive attitude about the coming birth, but
were simultaneously worried about the postnatal situation. CONCLUSIONS: The
findings illustrate the importance of inclusive care and adequate follow-up
routines for both expectant parents following a prenatal diagnosis. This includes
the initial emotional shock, the decisional process, and depending on decision
reached, the termination or continuation of the pregnancy. Expectant fathers
presented with a fetal anomaly need adequate follow-up routines to address
worries about risk of recurrence in future pregnancies and worries about the
postnatal situation.
PMID- 29329526
TI - Definitions, measurements and prevalence of fear of childbirth: a systematic
review.
AB - BACKGROUND: Fear of Childbirth (FOC) is a common problem affecting women's health
and wellbeing, and a common reason for requesting caesarean section. The aims of
this review were to summarise published research on prevalence of FOC in
childbearing women and how it is defined and measured during pregnancy and
postpartum, and to search for useful measures of FOC, for research as well as for
clinical settings. METHODS: Five bibliographic databases in March 2015 were
searched for published research on FOC, using a protocol agreed a priori. The
quality of selected studies was assessed independently by pairs of authors.
Prevalence data, definitions and methods of measurement were extracted
independently from each included study by pairs of authors. Finally, some of the
country rates were combined and compared. RESULTS: In total, 12,188 citations
were identified and screened by title and abstract; 11,698 were excluded and full
text of 490 assessed for analysis. Of these, 466 were excluded leaving 24 papers
included in the review, presenting prevalence of FOC from nine countries in
Europe, Australia, Canada and the United States. Various definitions and
measurements of FOC were used. The most frequently-used scale was the W-DEQ with
various cut-off points describing moderate, severe/intense and extreme/phobic
fear. Different 3-, 4-, and 5/6 point scales and visual analogue scales were also
used. Country rates (as measured by seven studies using W-DEQ with >=85 cut-off
point) varied from 6.3 to 14.8%, a significant difference (chi-square = 104.44,
d.f. = 6, p < 0.0001). CONCLUSIONS: Rates of severe FOC, measured in the same
way, varied in different countries. Reasons why FOC might differ are unknown, and
further research is necessary. Future studies on FOC should use the W-DEQ tool
with a cut-off point of >=85, or a more thoroughly tested version of the FOBS
scale, or a three-point scale measurement of FOC using a single question as 'Are
you afraid about the birth?' In this way, valid comparisons in research can be
made. Moreover, validation of a clinical tool that is more focussed on FOC alone,
and easier than the longer W-DEQ, for women to fill in and clinicians to
administer, is required.
PMID- 29329528
TI - Transmission of measles among healthcare Workers in Hospital W, Xinjiang
Autonomous Region, China, 2016.
AB - BACKGROUND: As China approaches the elimination of measles, outbreaks of measles
continue to occur. Healthcare workers (HCWs) are known to be at high risk of
infection and transmission of measles virus. A measles outbreak occurred in a
hospital in Xinjiang Uighur Autonomous Region of the People's Republic of China.
We report an investigation of this outbreak and its implications for measles
elimination and outbreak preparedness. METHODS: We conducted a retrospective
search for measles cases using hospital records. Information on cases was
collected by interview, and was used to determine epidemiological linkages. We
surveyed HCWs to determine their demographic characteristics, disease history and
vaccination status, and knowledge about measles. RESULTS: We identified 19 cases,
ages 18 to 45 years, in Hospital W between December 2015 and January 2016; 14
were laboratory-confirmed, and 5 were epidemiologically linked. The primary case
was a 25-year-old neurology department nurse who developed a rash on 22 December
2015 that was reported on 11 January 2016. She continued working and living with
her workmates in a dormitory during her measles transmission period. Among the 19
infected HCWs, 2 had received a dose of measles-containing vaccine (MCV) before
the outbreak, and 16 had unknown vaccination status. Outbreak response
immunization activities were started on 8 January in a non-selective manner by
offering vaccine regardless of vaccination history; 605(68%) of 890 HCWs were
vaccinated. The HCW survey had a 73% response rate (646/890); 41% of HCWs
reported that they had received MCV before outbreak, and 56% exhibited good
knowledge of measles symptoms, transmission, complications, and vaccination.
CONCLUSIONS: Low MCV coverage, low measles knowledge among HCWs, delayed
reporting of measles cases, and absence of proper case management were associated
with this outbreak. Training and vaccinating HCWs against measles are essential
activities to prevent measles virus transmission among HCWs.
PMID- 29329529
TI - Resilience and well-being of university nursing students in Hong Kong: a cross
sectional study.
AB - BACKGROUND: University nursing students experience higher levels of academic
stress than those of other disciplines. Academic stress leads to psychological
distress and has detrimental effects on well-being. The ability to overcome such
adversity and learn to be stronger from the experience is regarded as resilience.
Resilience is found to have an impact on learning experience, academic
performance, course completion and, in the longer term, professional practice.
Resilience and positive coping strategies can resist stress and improve personal
well-being. However, the relationship between resilience and well-being remains
unexplored in nursing students, which are significant attributes to their
academic success and future career persistence. METHODS: The study was a cross
sectional descriptive correlational design. Inclusion criteria for recruitment
was students studying pre-registration nursing programmes at both undergraduate
and postgraduate levels. The 10-item Connor-Davidson Resilience Scale (CD-RISC
10) and World Health Organisation-5 Well-Being Index (WHO-5) were used to measure
resilience and psychological well-being respectively. RESULTS: A convenience
sample of 678 university nursing students was recruited from a university. The
mean score of CD-RISC-10 was 24.0. When comparing the resilience levels of
undergraduate and postgraduate students, the total scores were found to be 23.8
and 24.9 respectively. There was a statistically significant difference between
the groups (p = .020). With regard to perceived well-being, the mean score of WHO
5 was 15.5. There was no significant difference between undergraduates and
postgraduates (p = .131). Bivariate analysis showed that self-reported resilience
had a medium, positive correlation with perceived well-being (r = .378, p =
.000), and senior students had significantly higher level of perceived well-being
than junior students (16.0 vs 15.1, p = .003). Multivariable regression analysis
on perceived well-being indicated that self-reported resilience emerged as a
significant predictor of perceived well-being (regression coefficient B = 0.259;
p < .001). CONCLUSIONS: The results demonstrate that nursing students with a high
level of resilience have better perceived well-being, and the level of resilience
of postgraduates was significantly higher than that of undergraduates. Therefore,
educational strategies should be developed in the nursing curriculum and a
supportive learning environment should be created to foster resilience in the
students.
PMID- 29329530
TI - Design and evaluation of a mobile application to assist the self-monitoring of
the chronic kidney disease in developing countries.
AB - BACKGROUND: The chronic kidney disease (CKD) is a worldwide critical problem,
especially in developing countries. CKD patients usually begin their treatment in
advanced stages, which requires dialysis and kidney transplantation, and
consequently, affects mortality rates. This issue is faced by a mobile health
(mHealth) application (app) that aims to assist the early diagnosis and self
monitoring of the disease progression. METHODS: A user-centered design (UCD)
approach involving health professionals (nurse and nephrologists) and target
users guided the development process of the app between 2012 and 2016. In-depth
interviews and prototyping were conducted along with healthcare professionals
throughout the requirements elicitation process. Elicited requirements were
translated into a native mHealth app targeting the Android platform. Afterward,
the Cohen's Kappa coefficient statistics was applied to evaluate the agreement
between the app and three nephrologists who analyzed test results collected from
60 medical records. Finally, eight users tested the app and were interviewed
about usability and user perceptions. RESULTS: A mHealth app was designed to
assist the CKD early diagnosis and self-monitoring considering quality attributes
such as safety, effectiveness, and usability. A global Kappa value of 0.7119
showed a substantial degree of agreement between the app and three nephrologists.
Results of face-to-face interviews with target users indicated a good user
satisfaction. However, the task of CKD self-monitoring proved difficult because
most of the users did not fully understand the meaning of specific biomarkers
(e.g., creatinine). CONCLUSION: The UCD approach provided mechanisms to develop
the app based on the real needs of users. Even with no perfect Kappa degree of
agreement, results are satisfactory because it aims to refer patients to
nephrologists in early stages, where they may confirm the CKD diagnosis.
PMID- 29329531
TI - Chemical genomic guided engineering of gamma-valerolactone tolerant yeast.
AB - BACKGROUND: Gamma valerolactone (GVL) treatment of lignocellulosic bomass is a
promising technology for degradation of biomass for biofuel production; however,
GVL is toxic to fermentative microbes. Using a combination of chemical genomics
with the yeast (Saccharomyces cerevisiae) deletion collection to identify
sensitive and resistant mutants, and chemical proteomics to monitor protein
abundance in the presence of GVL, we sought to understand the mechanism toxicity
and resistance to GVL with the goal of engineering a GVL-tolerant, xylose
fermenting yeast. RESULTS: Chemical genomic profiling of GVL predicted that this
chemical affects membranes and membrane-bound processes. We show that GVL causes
rapid, dose-dependent cell permeability, and is synergistic with ethanol.
Chemical genomic profiling of GVL revealed that deletion of the functionally
related enzymes Pad1p and Fdc1p, which act together to decarboxylate cinnamic
acid and its derivatives to vinyl forms, increases yeast tolerance to GVL.
Further, overexpression of Pad1p sensitizes cells to GVL toxicity. To improve GVL
tolerance, we deleted PAD1 and FDC1 in a xylose-fermenting yeast strain. The
modified strain exhibited increased anaerobic growth, sugar utilization, and
ethanol production in synthetic hydrolysate with 1.5% GVL, and under other
conditions. Chemical proteomic profiling of the engineered strain revealed that
enzymes involved in ergosterol biosynthesis were more abundant in the presence of
GVL compared to the background strain. The engineered GVL strain contained
greater amounts of ergosterol than the background strain. CONCLUSIONS: We found
that GVL exerts toxicity to yeast by compromising cellular membranes, and that
this toxicity is synergistic with ethanol. Deletion of PAD1 and FDC1 conferred
GVL resistance to a xylose-fermenting yeast strain by increasing ergosterol
accumulation in aerobically grown cells. The GVL-tolerant strain fermented sugars
in the presence of GVL levels that were inhibitory to the unmodified strain. This
strain represents a xylose fermenting yeast specifically tailored to GVL produced
hydrolysates.
PMID- 29329532
TI - Functionality of hospital information systems: results from a survey of quality
directors at Turkish hospitals.
AB - BACKGROUND: We aimed to determine availability of core Hospital Information
Systems (HIS) functions implemented in Turkish hospitals and the perceived
importance of these functions on quality and patient safety. METHODS: We surveyed
quality directors (QDs) at civilian hospitals in the nation of Turkey. Data were
collected via web survey using an instrument with 50 items describing core
functionality of HIS. We calculated mean availability of each function, mean and
median values of perceived impact on quality, and we investigated the
relationship between availability and perceived importance. RESULTS: We received
responses from 31% of eligible institutions, representing all major geographic
regions of Turkey. Mean availability of 50 HIS functions was 65.6%, ranging from
19.6% to 97.4%. Mean importance score was 7.87 (on a 9-point scale) ranging from
7.13 to 8.41. Functions related to result management (89.3%) and decision support
systems (52.2%) had the highest and lowest reported availability respectively.
Availability and perceived importance were moderately correlated (r = 0.52).
CONCLUSION: QDs report high importance of the HIS functions surveyed as they
relate to quality and patient safety. Availability and perceived importance of
HIS functions are generally correlated, with some interesting exceptions. These
findings may inform future investments and guide policy changes within the
Turkish healthcare system. Financial incentives, regulations around certified
HIS, revisions to accreditation manuals, and training interventions are all
policies which will help integrate HIS functions to support quality and patient
safety in Turkish hospitals.
PMID- 29329533
TI - Nutritional status of in-school children and its associated factors in
Denkyembour District, eastern region, Ghana: comparing schools with feeding and
non-school feeding policies.
AB - BACKGROUND: Childhood malnutrition still remains a major public health problem
impacting negatively on the academic aptitude of school-aged children (SAC)
particularly in limited resource countries. The Government of Ghana in
collaboration with the Dutch Government introduced the school feeding programme
(SFP) to boost the nutritional status of SAC in the country. This study sought to
compare the nutritional status of SAC enrolled in schools with the SFP and SAC
enrolled in schools without the SFP in place for the purpose of identifying which
group has the higher rate of malnutrition. METHODS: A multi-stage sampling was
used to select 359 SAC between 5 and 12 years who are enrolled in primary one to
six. Twelve public schools were selected, of which 6 schools benefit from the SFP
and the other six do not. Anthropometric measurements were conducted for the
subjects and SPSS version 20.0 was used for data entry and analysis. Chi square
test was carried out to determine the difference between the two groups of
schools. RESULTS: Of the total of 359 subjects, 55.1% were from schools that do
not implement the SFP and 44.9% were from schools that implement the SFP. The
prevalence of stunting among children in schools on the SFP was 16.2% compared
with 17.2% among children in schools that do not implement the SFP. The
prevalence of thinness was two times higher (9.3%) among children in schools on
the SFP than in children in schools that do not implement the SFP (4.6%) (p =
0.028). The prevalence of overweight among children in schools on the SFP was
1.9% and 0.0% for children in schools that do not implement the SFP. Sub
district, sex, age of pupil, area of residence and community type were
significantly associated with stunting (p = 0.002), (p = 0.008), (p = 0.008), (p
< 0.001) and (p = 0.007) respectively. CONCLUSION: Overweight and thinness were
higher among children in schools on SFP than in children in schools without SFP.
An evaluation of the implementation of the school feeding programme is
recommended for future studies.
PMID- 29329534
TI - A large-scale study of a poultry trading network in Bangladesh: implications for
control and surveillance of avian influenza viruses.
AB - BACKGROUND: Since its first report in 2007, avian influenza (AI) has been endemic
in Bangladesh. While live poultry marketing is widespread throughout the country
and known to influence AI dissemination and persistence, trading patterns have
not been described. The aim of this study is to assess poultry trading practices
and features of the poultry trading networks which could promote AI spread, and
their potential implications for disease control and surveillance. Data on
poultry trading practices was collected from 849 poultry traders during a cross
sectional survey in 138 live bird markets (LBMs) across 17 different districts of
Bangladesh. The quantity and origins of traded poultry were assessed for each
poultry type in surveyed LBMs. The network of contacts between farms and LBMs
resulting from commercial movements of live poultry was constructed to assess its
connectivity and to identify the key premises influencing it. RESULTS: Poultry
trading practices varied according to the size of the LBMs and to the type of
poultry traded. Industrial broiler chickens, the most commonly traded poultry,
were generally sold in LBMs close to their production areas, whereas ducks and
backyard chickens were moved over longer distances, and their transport involved
several intermediates. The poultry trading network composed of 445 nodes (73.2%
were LBMs) was highly connected and disassortative. However, the removal of only
5.6% of the nodes (25 LBMs with the highest betweenness scores), reduced the
network's connectedness, and the maximum size of output and input domains by more
than 50%. CONCLUSIONS: Poultry types need to be discriminated in order to
understand the way in which poultry trading networks are shaped, and the level of
risk of disease spread that these networks may promote. Knowledge of the network
structure could be used to target control and surveillance interventions to a
small number of LBMs.
PMID- 29329535
TI - Measurement of the potential geographic accessibility from call to definitive
care for patient with acute stroke.
AB - BACKGROUND: The World Health Organization refers to stroke, the second most
frequent cause of death in the world, in terms of pandemic. Present treatments
are only effective within precise time windows. Only 10% of thrombolysis patients
are eligible. Late assessment of the patient resulting from admission and lack of
knowledge of the symptoms is the main explanation of lack of eligibility.
METHODS: The aim is the measurement of the time of access to treatment facilities
for stroke victims, using ambulances (firemen ambulances or EMS ambulances) and
private car. The method proposed analyses the potential geographic accessibility
of stroke care infrastructure in different scenarios. The study allows better
considering of the issues inherent to an area: difficult weather conditions,
traffic congestion and failure to respect the distance limits of emergency
transport. RESULTS: Depending on the scenario, access times vary considerably
within the same commune. For example, between the first and the second scenario
for cities in the north of Rhone county, there is a 10 min difference to the
nearest Primary Stroke Center (PSC). For the first scenario, 90% of the
population is 20 min away of the PSC and 96% for the second scenario. Likewise,
depending on the modal vector (fire brigade or emergency medical service),
overall accessibility from the emergency call to admission to a Comprehensive
Stroke Center (CSC) can vary by as much as 15 min. CONCLUSIONS: The setting up of
the various scenarios and modal comparison based on the calculation of overall
accessibility makes this a new method for calculating potential access to care
facilities. It is important to take into account the specific pathological
features and the availability of care facilities for modelling. This method is
innovative and recommendable for measuring accessibility in the field of health
care. This study makes possible to highlight the patients' extension of care
delays. Thus, this can impact the improvement of patient care and rethink the
healthcare organization. Stroke is addressed here but it is applicable to other
pathologies.
PMID- 29329536
TI - Dietary flavonoid intake in older adults: how many days of dietary assessment are
required and what is the impact of seasonality?
AB - BACKGROUND: Within- and between-person variation in nutrient intake is well
established, but little is known about variability in dietary flavonoid intake,
including the effect of seasonality. METHODS: Within- and between-individual
variability of flavonoid intake, and intake of flavonoid subclasses was examined
in older adults (n = 79; mean age 70.1 y (range: 60y-80y)), using three separate
4-day weighed food records (WFR) collected approximately 4 months apart. The
effects of seasonality were also examined. Mixed-effects linear regression models
were used to estimate within- and between-individual variance components for
flavonoids and subclasses. The number of days of dietary assessment required for
a high level of hypothetical accuracy was calculated from variance ratios.
RESULTS: Within- and between-individual variability was high for flavonoid
intake, and intake of flavonoid subclasses, with variance ratios > 1. It was
calculated that six days of WFR data are required for total flavonoid intake, and
between 6 and 10 days was required for flavonoid subclasses. There was no effect
of seasonality for total flavonoid intake or intake of flavonoid subclasses, with
the exception that flavan-3-ol and flavanone intakes which were relatively low in
summer, and in summer and winter, respectively. CONCLUSION: While the effects of
seasonality on total flavonoid intake may be small, within- and between
individual variation associated with flavonoid intake assessment appears to be
substantial across 12 days of WFR data in older adults. It is recommended that a
minimum of 6 days of weighed food records are collected to minimise the impact of
within- and between-individual variability on total flavonoid intake assessments
in this population.
PMID- 29329538
TI - Peripheral blood gene expression signatures which reflect smoking and aspirin
exposure are associated with cardiovascular events.
AB - BACKGROUND: Cardiovascular disease and its sequelae are major causes of global
mortality, and better methods are needed to identify patients at risk for future
cardiovascular events. Gene expression analysis can inform on the molecular
underpinnings of risk factors for cardiovascular events. Smoking and aspirin have
known opposing effects on platelet reactivity and MACE, however their effects on
each other and on MACE are not well described. METHODS: We measured peripheral
blood gene expression levels of ITGA2B, which is upregulated by aspirin and
correlates with platelet reactivity on aspirin, and a 5 gene validated smoking
gene expression score (sGES) where higher expression correlates with smoking
status, in participants from the previously reported PREDICT trial (NCT
00500617). The primary outcome was a composite of death, myocardial infarction,
and stroke/TIA (MACE). We tested whether selected genes were associated with MACE
risk using logistic regression. RESULTS: Gene expression levels were determined
in 1581 subjects (50.5% female, mean age 60.66 +/-11.46, 18% self-reported
smokers); 3.5% of subjects experienced MACE over 12 months follow-up. Elevated
sGES and ITGA2B expression were each associated with MACE (odds ratios [OR] =1.16
[95% CI 1.10-1.31] and 1.42 [95% CI 1.00-1.97], respectively; p < 0.05). ITGA2B
expression was inversely associated with self-reported smoking status and the
sGES (p < 0.001). A logistic regression model combining sGES and ITGA2B showed
better performance (AIC = 474.9) in classifying MACE subjects than either alone
(AIC = 479.1, 478.2 respectively). CONCLUSION: Gene expression levels associated
with smoking and aspirin are independently predictive of an increased risk of
cardiovascular events.
PMID- 29329537
TI - The HIV-1 accessory proteins Nef and Vpu downregulate total and cell surface CD28
in CD4+ T cells.
AB - BACKGROUND: The HIV-1 accessory proteins Nef and Vpu alter cell surface levels of
multiple host proteins to modify the immune response and increase viral
persistence. Nef and Vpu can downregulate cell surface levels of the co
stimulatory molecule CD28, however the mechanism of this function has not been
completely elucidated. RESULTS: Here, we provide evidence that Nef and Vpu
decrease cell surface and total cellular levels of CD28. Moreover, using
inhibitors we implicate the cellular degradation machinery in the downregulation
of CD28. We shed light on the mechanisms of CD28 downregulation by implicating
the Nef LL165 and DD175 motifs in decreasing cell surface CD28 and Nef DD175 in
decreasing total cellular CD28. Moreover, the Vpu LV64 and S52/56 motifs were
required for cell surface CD28 downregulation, while, unlike for CD4
downregulation, Vpu W22 was dispensable. The Vpu S52/56 motif was also critical
for Vpu-mediated decreases in total CD28 protein level. Finally, the ability of
Vpu to downregulate CD28 is conserved between multiple group M Vpu proteins and
infection with viruses encoding or lacking Nef and Vpu have differential effects
on activation upon stimulation. CONCLUSIONS: We report that Nef and Vpu
downregulate cell surface and total cellular CD28 levels. We identified
inhibitors and mutations within Nef and Vpu that disrupt downregulation, shedding
light on the mechanisms utilized to downregulate CD28. The conservation and
redundancy between the abilities of two HIV-1 proteins to downregulate CD28
highlight the importance of this function, which may contribute to the
development of latently infected cells.
PMID- 29329539
TI - State-dependent domicile leaving rates in Anopheles gambiae.
AB - BACKGROUND: Transmission of Plasmodium greatly depends on the foraging behaviour
of its mosquito vector (Anopheles spp.). The accessibility of blood hosts and
availability of plant sugar (i.e., nectar) sources, together with mosquito energy
state, have been shown to modulate blood feeding (and thus biting rates) of
anopheline mosquitoes. In this study, the influence of mosquito starvation status
and availability of nectar on the decision of female Anopheles gambiae mosquitoes
to leave a bed net-protected blood host was examined. METHODS: Two small-scale
mesocosm experiments were conducted using female mosquitoes starved for 0, 24 or
48 h, that were released inside a specially constructed hut with mesh-sealed
exits and containing a bed net-protected human volunteer. Floral cues were
positioned on one side of the hut or the other. Several biologically plausible
exponential decay models were developed that characterized the emigration rates
of mosquitoes from the huts. These varied from simple random loss to leaving
rates dependent upon energy state and time. These model fits were evaluated by
examining their fitted parameter estimates and comparing Akaike information
criterion. RESULTS: Starved mosquitoes left domiciles at a higher rate than
recently fed individuals however, there was no difference between 1- and 2-day
starved mosquitoes. There was also no effect of floral cue placement. The best
fitting emigration model was one based on both mosquito energy state and time
whereas the worst fitting model was one based on the assumption of constant
leaving rates, independent of time and energy state. CONCLUSIONS: The results
confirm that mosquito-leaving behaviour is energy-state dependent, and provide
some of the first evidence of state-dependent domicile emigration in An. gambiae,
which may play a role in malarial transmission dynamics. Employment of simple,
first-principle, mechanistic models can be very useful to our understanding of
why and how mosquitoes leave domiciles.
PMID- 29329540
TI - Children with albinism in African regions: their rights to 'being' and 'doing'.
AB - BACKGROUND: Albinism is an inherited condition with a relatively high prevalence
in populations throughout sub-Saharan Africa. People with oculocutaneous albinism
have little or no pigment in their hair, skin and eyes; thus they are visually
impaired and extremely sensitive to the damaging effect of the sun on their skin.
Aside from the health implications of oculocutaneous albinism, there are also
significant sociocultural risks. The impacts of albinism are particularly serious
in areas that associate albinism with legend and folklore, leading to
stigmatisation and discrimination. In regions of Africa those with albinism may
be assaulted and sometimes killed for their body parts for use in witchcraft
related rites or to make 'lucky' charms. There is a dearth of research on the
psychosocial aspects of albinism and particularly on how albinism impacts on the
everyday lives of people with albinism. DISCUSSION: There is a growing
recognition and acceptance in Africa that people with albinism should be
considered disabled. Thomas's social-relational model of disability proposes it
is essential to understand both the socio-structural barriers and restrictions
that exclude disabled people (barriers to doing); and the social processes and
practices which can negatively affect their psycho-emotional wellbeing (barriers
to being). In this article, we combine a social model of disability with
discussion on human rights to address the lacuna surrounding the psychosocial and
daily experiences of people with albinism. CONCLUSION: Through using this
combined framework we conclude that the rights of people with albinism in some
regions of Africa are not being enacted. Our debate highlights the need to
develop a holistic concept of rights for children and young people with albinism
which sees human rights as indivisible. We illuminate some of the specific ways
in which the lives of children with albinism could be improved by addressing
'barriers to being' and 'barriers to doing', at the heart of which requires a
shift in attitude and action to address discrimination.
PMID- 29329541
TI - A role for endothelial nitric oxide synthase in intestinal stem cell
proliferation and mesenchymal colorectal cancer.
AB - BACKGROUND: Nitric oxide (NO) has been highlighted as an important agent in
cancer-related events. Although the inducible nitric oxide synthase (iNOS)
isoform has received most attention, recent studies in the literature indicate
that the endothelial isoenzyme (eNOS) can also modulate different tumor processes
including resistance, angiogenesis, invasion, and metastasis. However, the role
of eNOS in cancer stem cell (CSC) biology and mesenchymal tumors is unknown.
RESULTS: Here, we show that eNOS was significantly upregulated in VilCre ERT2 Apc
fl/+ and VilCre ERT2 Apc fl/fl mouse intestinal tissue, with intense
immunostaining in hyperproliferative crypts. Similarly, the more invasive VilCre
ERT2 Apc fl/+ Pten fl/+ mouse model showed an overexpression of eNOS in
intestinal tumors whereas this isoform was not expressed in normal tissue.
However, none of the three models showed iNOS expression. Notably, when 40 human
colorectal tumors were classified into different clinically relevant molecular
subtypes, high eNOS expression was found in the poor relapse-free and overall
survival mesenchymal subtype, whereas iNOS was absent. Furthermore, Apc fl/fl
organoids overexpressed eNOS compared with wild-type organoids and NO depletion
with the scavenger carboxy-PTIO (c-PTIO) decreased the proliferation and the
expression of stem-cell markers, such as Lgr5, Troy, Vav3, and Slc14a1, in these
intestinal organoids. Moreover, specific NO depletion also decreased the
expression of CSC-related proteins in human colorectal cancer cells such as beta
catenin and Bmi1, impairing the CSC phenotype. To rule out the contribution of
iNOS in this effect, we established an iNOS-knockdown colorectal cancer cell
line. NO-depleted cells showed a decreased capacity to form tumors and c-PTIO
treatment in vivo showed an antitumoral effect in a xenograft mouse model.
CONCLUSION: Our data support that eNOS upregulation occurs after Apc loss,
emerging as an unexpected potential new target in poor-prognosis mesenchymal
colorectal tumors, where NO scavenging could represent an interesting therapeutic
alternative to targeting the CSC subpopulation.
PMID- 29329542
TI - Relative validity of a web-based food frequency questionnaire for Danish
adolescents.
AB - BACKGROUND: With increased focus on dietary intake among youth and risk of
diseases later in life, it is of importance, prior to assessing diet-disease
relationships, to examine the validity of the dietary assessment tool. This
study's objective was to evaluate the relative validity of a self-administered
web-based FFQ among Danish children aged 12 to 15 years. METHODS: From a nested
sub-cohort within the Danish National Birth Cohort, 124 adolescents participated.
Four weeks after completion of the FFQ, adolescents were invited to complete
three telephone-based 24HRs; administered 4 weeks apart. Mean or median intakes
of nutrients and food groups estimated from the FFQ were compared with the mean
of 3x24HRs. To assess the level of ranking we calculated the proportion of
correctly classified into the same quartile, and the proportion of misclassified
(into the opposite quartile). Spearman's correlation coefficients and de
attenuated coefficients were calculated to assess agreement between the FFQ and
24HRs. RESULTS: The mean percentage of all food groups, for adolescents
classified into the same and opposite quartile was 35 and 7.5%, respectively.
Mean Spearman's correlation was 0.28 for food groups and 0.35 for nutrients,
respectively. Adjustment for energy and within-person variation in the 24HRs had
little effect on the magnitude of the correlations for food groups and nutrients.
We found overestimation by the FFQ compared with the 24HRs for fish, fruits,
vegetables, oils and dressing and underestimation by the FFQ for meat/poultry and
sweets. Median intake of beverages, dairy, bread, cereals, the mean total energy
and carbohydrate intake did not differ significantly between the two methods.
CONCLUSION: The relative validity of the FFQ compared with the 3x24HRs showed
that the ranking ability differed across food groups and nutrients with best
ranking for estimated intake of dairy, fruits, and oils and dressing. Larger
variation was observed for fish, sweets and vegetables. For nutrients, the
ranking ability was acceptable for fatty acids and iron. When evaluating
estimates from the FFQ among Danish adolescents these findings should be
considered.
PMID- 29329543
TI - STAT3-induced lncRNA HAGLROS overexpression contributes to the malignant
progression of gastric cancer cells via mTOR signal-mediated inhibition of
autophagy.
AB - BACKGROUND: Long noncoding RNAs (lncRNAs) are an important class of functional
regulators involved in human cancers development, including gastric cancer (GC).
Studying aberrantly expressed lncRNAs may provide us with new insights into the
occurrence and development of gastric cancer by acting as oncogenes or tumor
suppressors. In this study, we aim to examine the expression pattern of lncRNA
HAGLROS in GC and its clinical significance as well as its biological role in
tumor progression. METHODS: Bioinformatics analysis and qRT-PCR were performed to
detect the relative expression of HAGLROS in GC tissues and cell lines. Gain or
loss of function approaches were used to investigate the biological functions of
HAGLROS. The effect of HAGLROS on proliferation was evaluated by MTT, colony
formation assay and nude mouse xenograft model. Wound healing and Transwell
assays were used to study the invasion and migration of GC cells. FISH, RIP, RNA
seq, Luciferase report assays, RNA pulldown and Western blot were fulfilled to
measure molecular mechanisms. Results are shown as means +/- S.D. and differences
were tested for significance using Student's t-test (two-tailed). RESULTS: We
screened out HAGLROS, whose expression was significantly increased and correlated
with outcomes of GC patients by publicly available lncRNAs expression profiling
and integrating analyses. Exogenous down-regulation of HAGLROS expression
significantly suppressed the cell proliferation, invasion and migration.
Mechanistic investigations showed that HAGLROS was a direct target of
transcriptional factor STAT3. Moreover, HAGLROS knockdown decreased mTOR
expression and increased autophagy-related genes ATG9A and ATG9B expression.
Further investigation showed that HAGLROS regulated mTOR signals in two manners.
In the one hand, HAGLROS competitively sponged miR-100-5p to increase mTOR
expression by antagonizing miR-100-5p-mediated mTOR mRNA inhibition. On the other
hand, HAGLROS interacted with mTORC1 components to activate mTORC1 signaling
pathway which was known to be an important negative signal of autophagy. Here
activation of mTORC1 signaling pathway by HAGLROS inhibited autophagy, thereby
promoted excessive proliferation and maintained the malignant phenotype of GC
cells. CONCLUSION: The present study demonstrates that HAGLROS overexpression
contributes to GC development and poor prognosis and will be a target for GC
therapy and further develop as a potential prognostic biomarker.
PMID- 29329544
TI - The importance of drug checking outside the context of nightlife in Slovenia.
AB - BACKGROUND: The main purpose of the research was to evaluate the implementation
of the drug checking service in Slovenia and to obtain the opinion of users
included in harm reduction programmes for high-risk drug users and of drug users
in nightlife settings on drug checking, the reasons for drug checking, and their
attitude towards adulterants in the drugs that they use. METHODS: The two final
unrepresentative research samples included 102 respondents from harm reduction
programmes and 554 respondents from the online sample. The questionnaire was
designed based on analysis of the interviews conducted with professionals from
the programmes, who took part in the drug checking project, and based on previous
research on drug use in nightlife. RESULTS: The main findings related to users'
opinions on the drug checking service are that users from both samples perceive
drug checking as a contribution to risk reduction and that they find providing
information for them about the harmful adulterants and substances that they use
very important. In addition, users from both samples considered accessibility of
the drug checking service as very important and would be in favour of brief
counselling at the collection of the drug sample. One of the salient differences
between samples was that nightlife drug users found it more important to
recognise substances in the drugs that they use. CONCLUSIONS: Drug users from two
different samples attach a relatively high importance to the drug checking
service, and they consider it to be a contribution to risk reduction. As well as
drug users in nightlife settings, high-risk drug users also perceive the drug
checking service to be important, which is relevant in the phase of planning drug
checking services outside the context of nightlife and for the act of
incorporating these services into contemporary harm reduction policy.
PMID- 29329545
TI - Use of epidemiological and entomological tools in the control and elimination of
malaria in Ethiopia.
AB - Malaria is the leading public health problem in Ethiopia where over 75% of the
land surface is at risk with varying intensities depending on altitude and
season. Although the mortality because of malaria infection has declined much
during the last 15-20 years, some researchers worry that this success story may
not be sustainable. Past notable achievements in the reduction of malaria disease
burden could be reversed in the future. To interrupt, or even to eliminate
malaria transmission in Ethiopia, there is a need to implement a wide range of
interventions that include insecticide-treated bed nets, indoor residual
spraying, improved control of residual malaria transmission, and improved
diagnostics, enhanced surveillance, and methods to deal with the emergence of
resistance both to drugs and to insecticides. Developments during the past years
with increasing awareness about the role of very low levels of malaria prevalence
can sustain infections, may also demand that tools not used in the routine
control efforts to reduce or eliminate malaria, should now be made available in
places where malaria transmission occurs.
PMID- 29329546
TI - Whole-genome sequencing of genotype VI Newcastle disease viruses from formalin
fixed paraffin-embedded tissues from wild pigeons reveals continuous evolution
and previously unrecognized genetic diversity in the U.S.
AB - BACKGROUND: Newcastle disease viruses (NDV) are highly contagious and cause
disease in both wild birds and poultry. A pigeon-adapted variant of genotype VI
NDV, often termed pigeon paramyxovirus 1, is commonly isolated from columbids in
the United States and worldwide. Complete genomic characterization of these
genotype VI viruses circulating in wild columbids in the United States is
limited, and due to the genetic variability of the virus, failure of rapid
diagnostic detection has been reported. Therefore, in this study, formalin-fixed
paraffin-embedded (FFPE) samples were subjected to next-generation sequencing
(NGS) to identify and characterize these circulating viruses, providing valuable
genetic information. NGS enables multiple samples to be deep-sequenced in
parallel. When used on FFPE samples, this methodology allows for retrospective
studies of infectious organisms. METHODS: FFPE wild pigeon tissue samples
(kidney, liver and spleen) from 10 mortality events in the U.S. between 2010 and
2016 were analyzed using NGS to detect and sequence NDV genomes from randomly
amplified total RNA. Results were compared to the previously published
immunohistochemistry (IHC) results conducted on the same samples. Additionally,
phylogenetic analyses were conducted on the complete and partial fusion gene and
complete genome coding sequences. RESULTS: Twenty-three out of 29 IHC-positive
FFPE pigeon samples were identified as positive for NDV by NGS. Positive samples
produced an average genome coverage of 99.6% and an average median depth of 199.
A previously described sub-genotype (VIa) and a novel sub-genotype (VIn) of NDV
were identified as the causative agent of 10 pigeon mortality events in the U.S.
from 2010 to 2016. The distribution of these viruses from the North American
lineages match the distribution of the Eurasian collared-doves and rock pigeons
in the U.S. CONCLUSIONS: This work reports the first successful evolutionary
study using deep sequencing of complete NDV genomes from FFPE samples of wild
bird origin. There are at least two distinct U.S. lineages of genotype VI NDV
maintained in wild pigeons that are continuously evolving independently from each
other and have no evident epidemiological connections to viruses circulating
abroad. These findings support the hypothesis that columbids are serving as
reservoirs of virulent NDV in the U.S.
PMID- 29329547
TI - Microfluidic co-culture of pancreatic tumor spheroids with stellate cells as a
novel 3D model for investigation of stroma-mediated cell motility and drug
resistance.
AB - BACKGROUND: Pancreatic stellate cells (PSCs), a major component of the tumor
microenvironment in pancreatic cancer, play roles in cancer progression as well
as drug resistance. Culturing various cells in microfluidic (microchannel)
devices has proven to be a useful in studying cellular interactions and drug
sensitivity. Here we present a microchannel plate-based co-culture model that
integrates tumor spheroids with PSCs in a three-dimensional (3D) collagen matrix
to mimic the tumor microenvironment in vivo by recapitulating epithelial
mesenchymal transition and chemoresistance. METHODS: A 7-channel microchannel
plate was prepared using poly-dimethylsiloxane (PDMS) via soft lithography. PANC
1, a human pancreatic cancer cell line, and PSCs, each within a designated
channel of the microchannel plate, were cultured embedded in type I collagen.
Expression of EMT-related markers and factors was analyzed using
immunofluorescent staining or Proteome analysis. Changes in viability following
exposure to gemcitabine and paclitaxel were measured using Live/Dead assay.
RESULTS: PANC-1 cells formed 3D tumor spheroids within 5 days and the number of
spheroids increased when co-cultured with PSCs. Culture conditions were optimized
for PANC-1 cells and PSCs, and their appropriate interaction was confirmed by
reciprocal activation shown as increased cell motility. PSCs under co-culture
showed an increased expression of alpha-SMA. Expression of EMT-related markers,
such as vimentin and TGF-beta, was higher in co-cultured PANC-1 spheroids
compared to that in mono-cultured spheroids; as was the expression of many other
EMT-related factors including TIMP1 and IL-8. Following gemcitabine exposure, no
significant changes in survival were observed. When paclitaxel was combined with
gemcitabine, a growth inhibitory advantage was prominent in tumor spheroids,
which was accompanied by significant cytotoxicity in PSCs. CONCLUSIONS: We
demonstrated that cancer cells grown as tumor spheroids in a 3D collagen matrix
and PSCs co-cultured in sub-millimeter proximity participate in mutual
interactions that induce EMT and drug resistance in a microchannel plate.
Microfluidic co-culture of pancreatic tumor spheroids with PSCs may serve as a
useful model for studying EMT and drug resistance in a clinically relevant
manner.
PMID- 29329548
TI - The cost of a pediatric neurocritical care program for traumatic brain injury: a
retrospective cohort study.
AB - BACKGROUND: Inpatient care for children with severe traumatic brain injury (sTBI)
is expensive, with inpatient charges averaging over $70,000 per case (Hospital
Inpatient, Children Only, National Statistics. Diagnoses- clinical classification
software (CCS) principal diagnosis category 85 coma, stupor, and brain damage,
and 233 intracranial injury. Diagnoses by Aggregate charges [
https://hcupnet.ahrq.gov/#setup ]). This ranks sTBI in the top quartile of
pediatric conditions with the greatest inpatient costs (Hospital Inpatient,
Children Only, National Statistics. Diagnoses- clinical classification software
(CCS) principal diagnosis category 85 coma, stupor, and brain damage, and 233
intracranial injury. Diagnoses by Aggregate charges [
https://hcupnet.ahrq.gov/#setup ]). The Brain Trauma Foundation developed sTBI
intensive care guidelines in 2003, with revisions in 2012 (Kochanek, Carney, et.
al. PCCM 3:S1-S2, 2012). These guidelines have been widely disseminated, and are
associated with improved health outcomes (Pineda, Leonard. et. al. LN 12:45-52,
2013), yet research on the cost of associated hospital care is limited. The
objective of this study was to assess the costs of providing hospital care to
sTBI patients through a guideline-based Pediatric Neurocritical Care Program
(PNCP) implemented at St. Louis Children's Hospital, a pediatric academic medical
center in the Midwest United States. METHODS: This is a retrospective cohort
study. We used multi-level regression to estimate pre-/post-implementation
effects of the PNCP program on inflation adjusted total cost of in-hospital sTBI
care. The study population included 58 pediatric patient discharges in the pre
PNCP implementation group (July 15, 1999 - September 17, 2005), and 59 post
implementation patient discharges (September 18, 2005 - January 15, 2012).
RESULTS: Implementation of the PNCP was associated with a non-significant
difference in the cost of care between the pre- and post-implementation periods
(ebeta = 1.028, p = 0.687). CONCLUSIONS: Implementation of the PNCP to support
delivery of guideline-based care for children with sTBI did not change the total
per-patient cost of in-hospital care. A key strength of this study was its use of
hospital cost data rather than charges. Future research should consider the
longitudinal post-hospitalization costs of this approach to sTBI care.
PMID- 29329549
TI - Near-infrared dye marking for thoracoscopic resection of small-sized pulmonary
nodules: comparison of percutaneous and bronchoscopic injection techniques.
AB - BACKGROUND: Minimally invasive video-assisted thoracoscopic surgery for small
sized pulmonary nodules is challenging, and image-guided preoperative
localisation is required. Near-infrared indocyanine green fluorescence is capable
of deep tissue penetration and can be distinguished regardless of the background
colour of the lung; thus, indocyanine green has great potential for use as a near
infrared fluorescent marker in video-assisted thoracoscopic surgery. METHODS:
Thirty-seven patients with small-sized pulmonary nodules, who were scheduled to
undergo video-assisted thoracoscopic wedge resection, were enrolled in this
study. A mixture of diluted indocyanine green and iopamidol was injected into the
lung parenchyma as a marker, using either computed tomography-guided percutaneous
or bronchoscopic injection techniques. Indications and limitations of the
percutaneous and bronchoscopic injection techniques for marking nodules with
indocyanine green fluorescence were examined and compared. RESULTS: In the
computed tomography-guided percutaneous injection group (n = 15), indocyanine
green fluorescence was detected in 15/15 (100%) patients by near-infrared
thoracoscopy. A small pneumothorax occurred in 3/15 (20.0%) patients, and
subsequent marking was unsuccessful after a pneumothorax occurred. In the
bronchoscopic injection group (n = 22), indocyanine green fluorescence was
detected in 21/22 (95.5%) patients. In 6 patients who underwent injection marking
at 2 different lesion sites, 5/6 (83.3%) markers were successfully detected.
CONCLUSION: Either computed tomography-guided percutaneous or bronchoscopic
injection techniques can be used to mark pulmonary nodules with indocyanine green
fluorescence. Indocyanine green is a safe and easily detectable fluorescent
marker for video-assisted thoracoscopic surgery. Furthermore, the bronchoscopic
injection approach enables surgeons to mark multiple lesion areas with less risk
of causing a pneumothorax. TRIAL REGISTRATION: UMIN-CTR R000027833 accepted by
ICMJE. Registered 5 January 2013.
PMID- 29329550
TI - Systematic quantitative analysis of H2A and H2B variants by targeted proteomics.
AB - BACKGROUND: Histones organize DNA into chromatin through a variety of processes.
Among them, a vast diversity of histone variants can be incorporated into
chromatin and finely modulate its organization and functionality. Classically,
the study of histone variants has largely relied on antibody-based assays.
However, antibodies have a limited efficiency to discriminate between highly
similar histone variants. RESULTS: In this study, we established a mass
spectrometry-based analysis to address this challenge. We developed a targeted
proteomics method, using selected reaction monitoring or parallel reaction
monitoring, to quantify a maximum number of histone variants in a single
multiplexed assay, even when histones are present in a crude extract. This
strategy was developed on H2A and H2B variants, using 55 peptides corresponding
to 25 different histone sequences, among which a few differ by a single amino
acid. The methodology was then applied to mouse testis extracts in which almost
all histone variants are expressed. It confirmed the abundance profiles of
several testis-specific histones during successive stages of spermatogenesis and
the existence of predicted H2A.L.1 isoforms. This methodology was also used to
explore the over-expression pattern of H2A.L.1 isoforms in a mouse model of male
infertility. CONCLUSIONS: Our results demonstrate that targeted proteomics is a
powerful method to quantify highly similar histone variants and isoforms. The
developed method can be easily transposed to the study of human histone variants,
whose abundance can be deregulated in various diseases.
PMID- 29329551
TI - Efficacy and safety of combined treatment of miniscalpel acupuncture and non
steroidal anti-inflammatory drugs: an assessor-blinded randomized controlled
pilot study.
AB - BACKGROUND: Chronic neck pain is a common musculoskeletal disease during the
lifespan of an individual. With an increase in dependence on computer technology,
the prevalence of chronic neck pain is expected to rise and this can lead to
socioeconomic problems. We have designed the current pilot study to evaluate the
efficacy and safety of miniscalpel acupuncture treatment combined with non
steroidal anti-inflammatory drugs (NSAIDs) in patients with chronic neck pain.
METHODS: This seven-week clinical trial has been designed as an assessor-blinded,
randomized controlled trial with three parallel arms. Thirty-six patients will be
recruited and randomly allocated to three treatment groups: miniscalpel
acupuncture treatment; NSAIDs; and miniscalpel acupuncture treatment combined
with NSAIDs. Patients in the miniscalpel acupuncture and combined treatment
groups will receive three sessions of miniscalpel acupuncture over a three-week
period. Patients in the NSAIDs and combined treatment groups will receive
zaltoprofen (one oral tablet, three times a day for three weeks). Primary and
secondary outcomes will be measured at weeks 0 (baseline), 1, 2, 3 (primary end
point), and 7 (four weeks after treatment completion) using the visual analogue
scale and the Neck Disability Index, EuroQol 5-dimension questionnaire, and
Patients' Global Impression of Change scale, respectively. Adverse events will
also be recorded. DISCUSSION: This pilot study will provide a basic foundation
for a future large-scale trial as well as information about the feasibility of
miniscalpel acupuncture treatment combined with NSAIDs for chronic neck pain.
TRIAL REGISTRATION: Korean Clinical Research Information Service registry,
KCT0002258 . Registered on 9 March 2017.
PMID- 29329552
TI - Correction to: Linkage, whole genome sequence, and biological data implicate
variants in RAB10 in Alzheimer's disease resilience.
AB - CORRECTION: The original version of this article [1] unfortunately contained a
typographical error. The 'Alzheimer's Disease Neuroimaging Initiative' was
erroneously included as 'Alzheimer's Disease Neuroimaging Initative' in the
author list of the article.
PMID- 29329554
TI - Correction to: Detection and full genome characterization of two beta CoV viruses
related to Middle East respiratory syndrome from bats in Italy.
AB - CORRECTION: After Publication of the article [1], it has been brought to our
attention that an author's name has been spelt incorrectly. The correct spelling
should be "Massimo Ciccozzi", but it was previously included as "Massimo
Cicozzi". The original version has now been revised to reflect this.
PMID- 29329553
TI - Inhibitors of the integrase-transportin-SR2 interaction block HIV nuclear import.
AB - BACKGROUND: Combination antiretroviral therapy efficiently suppresses HIV
replication in infected patients, transforming HIV/AIDS into a chronic disease.
Viral resistance does develop however, especially under suboptimal treatment
conditions such as poor adherence. As a consequence, continued exploration of
novel targets is paramount to identify novel antivirals that do not suffer from
cross-resistance with existing drugs. One new promising class of targets are HIV
protein-cofactor interactions. Transportin-SR2 (TRN-SR2) is a beta-karyopherin
that was recently identified as an HIV-1 cofactor. It has been implicated in
nuclear import of the viral pre-integration complex and was confirmed as a direct
binding partner of HIV-1 integrase (IN). Nevertheless, consensus on its mechanism
of action is yet to be reached. RESULTS: Here we describe the development and use
of an AlphaScreen-based high-throughput screening cascade for small molecule
inhibitors of the HIV-1 IN-TRN-SR2 interaction. False positives and nonspecific
protein-protein interaction inhibitors were eliminated through different
counterscreens. We identified and confirmed 2 active compound series from an
initial screen of 25,608 small molecules. These compounds significantly reduced
nuclear import of fluorescently labeled HIV particles. CONCLUSIONS: Alphascreen
based high-throughput screening can allow the identification of compounds
representing a novel class of HIV inhibitors. These results corroborate the role
of the IN-TRN-SR2 interaction in nuclear import. These compounds represent the
first in class small molecule inhibitors of HIV-1 nuclear import.
PMID- 29329555
TI - Exercise during and after neoadjuvant rectal cancer treatment (the EXERT trial):
study protocol for a randomized controlled trial.
AB - BACKGROUND: Standard treatment for locally advanced rectal cancer includes 5-6
weeks of neoadjuvant chemoradiotherapy (NACRT) followed by total mesorectal
excision 6-8 weeks later. NACRT improves local disease control and surgical
outcomes but also causes side effects including fatigue, diarrhea, hand-foot
syndrome, and physical deconditioning that may impede quality of life (QoL),
treatment completion, treatment response, and long-term prognosis. Interventions
to improve treatment outcomes and manage side effects that are safe, tolerable
and low-cost are highly desirable. Exercise has been shown to improve some of
these outcomes in other cancer patient groups but no study to date has examined
the potential benefits (and harms) of exercise training during and after NACRT
for rectal cancer. METHODS/DESIGN: The Exercise During and After Neoadjuvant
Rectal Cancer Treatment (EXERT) trial is a single-center, prospective, two-armed,
phase II randomized controlled trial designed to test the preliminary efficacy of
exercise training in this clinical setting and to further evaluate its
feasibility and safety. Participants will be 60 rectal cancer patients scheduled
to receive long-course NACRT followed by total mesorectal excision. Participants
will be randomly assigned to exercise training or usual care. Participants in the
exercise training group will be asked to complete three supervised, high
intensity interval training sessions/week during NACRT and >= 150 min/week of
unsupervised, moderate-to-vigorous-intensity, continuous exercise training after
NACRT prior to surgery. Participants in the usual care group will be asked not to
increase their exercise from baseline. Assessments will be completed pre NACRT,
post NACRT, and pre surgery. The primary endpoint will be cardiorespiratory
fitness (VO2 peak) at the post-NACRT time point assessed by a graded exercise
test. Secondary endpoints will include functional fitness assessed by the
Senior's Fitness Test, QoL assessed by the European Organisation of Research and
Treatment of Cancer, and symptom management assessed by the M.D. Anderson Symptom
Inventory. Exploratory clinical endpoints will include treatment toxicities,
treatment completion, treatment response, and surgical complications. DISCUSSION:
If the preliminary findings of EXERT are positive, additional research will be
warranted to confirm whether exercise is an innovative treatment to maintain QoL,
manage side effects, and/or improve treatment outcomes in rectal cancer patients.
TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03082495 . Registered on 9
February, 2017.
PMID- 29329556
TI - Cancer immunotherapy beyond immune checkpoint inhibitors.
AB - Malignant cells have the capacity to rapidly grow exponentially and spread in
part by suppressing, evading, and exploiting the host immune system.
Immunotherapy is a form of oncologic treatment directed towards enhancing the
host immune system against cancer. In recent years, manipulation of immune
checkpoints or pathways has emerged as an important and effective form of
immunotherapy. Agents that target cytotoxic T lymphocyte-associated molecule-4
(CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death
ligand-1 (PD-L1) are the most widely studied and recognized. Immunotherapy,
however, extends beyond immune checkpoint therapy by using new molecules such as
chimeric monoclonal antibodies and antibody drug conjugates that target malignant
cells and promote their destruction. Genetically modified T cells expressing
chimeric antigen receptors are able to recognize specific antigens on cancer
cells and subsequently activate the immune system. Native or genetically modified
viruses with oncolytic activity are of great interest as, besides destroying
malignant cells, they can increase anti-tumor activity in response to the release
of new antigens and danger signals as a result of infection and tumor cell lysis.
Vaccines are also being explored, either in the form of autologous or allogenic
tumor peptide antigens, genetically modified dendritic cells that express tumor
peptides, or even in the use of RNA, DNA, bacteria, or virus as vectors of
specific tumor markers. Most of these agents are yet under development, but they
promise to be important options to boost the host immune system to control and
eliminate malignancy. In this review, we have provided detailed discussion of
different forms of immunotherapy agents other than checkpoint-modifying drugs.
The specific focus of this manuscript is to include first-in-human phase I and
phase I/II clinical trials intended to allow the identification of those drugs
that most likely will continue to develop and possibly join the immunotherapeutic
arsenal in a near future.
PMID- 29329557
TI - One-year risk of serious infection in patients treated with certolizumab pegol as
compared with other TNF inhibitors in a real-world setting: data from a national
U.S. rheumatoid arthritis registry.
AB - BACKGROUND: Registry studies provide a valuable source of comparative safety data
for tumor necrosis factor inhibitors (TNFi) used in rheumatoid arthritis (RA),
but they are subject to channeling bias. Comparing safety outcomes without
accounting for channeling bias can lead to inaccurate comparisons between TNFi
prescribed at different stages of the disease. In the present study, we examined
the incidence of serious infection and other adverse events during certolizumab
pegol (CZP) use vs other TNFi in a U.S. RA cohort before and after using a
methodological approach to minimize channeling bias. METHODS: Patients with RA
enrolled in the Corrona registry, aged >= 18 years, initiating CZP or other TNFi
(etanercept, adalimumab, golimumab, or infliximab) after May 1, 2009 (n = 6215
initiations), were followed for <= 12 months. A propensity score (PS) model was
used to control for baseline characteristics associated with the probability of
receiving CZP vs other TNFi. Incidence rate ratios (IRRs) of serious infectious
events (SIEs), malignancies, and cardiovascular events (CVEs) in the CZP group vs
other TNFi group were calculated with 95% CIs, before and after PS matching.
RESULTS: Patients were more likely to initiate CZP later in the course of therapy
than those initiating other TNFi. CZP initiators (n = 975) were older and had
longer disease duration, more active disease, and greater disability than other
TNFi initiators (n = 5240). After PS matching, there were no clinically important
differences between CZP (n = 952) and other TNFi (n = 952). Before PS matching,
CZP was associated with a greater incidence of SIEs (IRR 1.53 [95% CI 1.13,
2.05]). The risk of SIEs was not different between groups after PS matching (IRR
1.26 [95% CI 0.84, 1.90]). The 95% CI of the IRRs for malignancies or CVEs
included unity, regardless of PS matching, suggesting no difference in risk
between CZP and other TNFi. CONCLUSIONS: After using PS matching to minimize
channeling bias and compare patients with a similar likelihood of receiving CZP
or other TNFi, the 1-year risk of SIEs, malignancies, and CVEs was not
distinguishable between the two groups.
PMID- 29329558
TI - Quality of life and problems associated with obturators of patients with
maxillectomies.
AB - BACKGROUND: Maxillary defects predispose patients to different undesirable
effects. The aim of this study was to assess the quality of life (QoL) of
patients with maxillary defects (acquired/congenital) wearing obturators.
METHODS: The study comprised 30 patients aged between 16 and 78 years. Interviews
were conducted to collect information pertaining to patients; sociodemographic,
self-reported function of obturator using Obturator Functioning Scale (OFS), self
evaluation of general health using Visual Analogue Scale (VAS), radiotherapy
treatment, salivary gland removal, reconstructive surgery, neck dissection and
length of time obturators were worn. Clinical examination included type of
maxillectomy, Aramany classification of the defect, and evaluation of obturator
function using the Kapur retention and stability scoring system. RESULT: Quality
of life was affected significantly by marital status (P = 0.026). Married
patients had better quality of life 61.3%, followed by divorced patients 38.8%,
widowed 37.3% and the least QoL was detected in single patients 36.5%.
Significant association between the type of maxillectomy and QoL was detected (P
= 0.002). Retention of obturator prosthesis had a highly significant association
with QoL (P < 0.001). Type of maxillectomy had a significant relation with
obturator retention (P = 0.005). Stability had a significant correlation with QoL
(P = 0.022). Obturator wearers who were treated with radiotherapy had lower QoL
than those who were not treated with radiotherapy. CONCLUSION: Rehabilitation of
patients with maxillary defects using obturator prosthesis is an appropriate and
not invasive treatment modality. Results support that good obturators contribute
to a better life quality.
PMID- 29329559
TI - SImplification of Medications Prescribed to Long-tErm care Residents (SIMPLER):
study protocol for a cluster randomised controlled trial.
AB - BACKGROUND: Complex medication regimens are highly prevalent in residential aged
care facilities (RACFs). Strategies to reduce unnecessary complexity may be
valuable because complex medication regimens can be burdensome for residents and
are costly in terms of nursing time. The aim of this study is to investigate
application of a structured process to simplify medication administration in
RACFs. METHODS: SImplification of Medications Prescribed to Long-tErm care
Residents (SIMPLER) is a non-blinded, matched-pair, cluster randomised controlled
trial of a single multidisciplinary intervention to simplify medication regimens.
Trained study nurses will recruit English-speaking, permanent residents from
eight South Australian RACFs. Medications taken by residents in the intervention
arm will be assessed once using a structured tool (the Medication Regimen
Simplification Guide for Residential Aged CarE) to identify opportunities to
reduce medication regimen complexity (e.g. by administering medications at the
same time, or through the use of longer-acting or combination formulations).
Residents in the comparison group will receive routine care. Participants will be
followed for up to 36 months after study entry. The primary outcome measure will
be the total number of charted medication administration times at 4 months after
study entry. Secondary outcome measures will include time spent administering
medications, medication incidents, resident satisfaction, quality of life, falls,
hospitalisation and mortality. Individual-level analyses that account for
clustering will be undertaken to determine the impact of the intervention on the
study outcomes. DISCUSSION: Ethical approval has been obtained from the Monash
University Human Research Ethics Committee and the aged care provider
organisation. Research findings will be disseminated through conference
presentations and peer-reviewed publications. SIMPLER will enable an improved
understanding of the burden of medication use in RACFs and quantify the impact of
regimen simplification on a range of outcomes important to residents and care
providers. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry,
ACTRN12617001060336 . Retrospectively registered on 20 July 2017.
PMID- 29329562
TI - Granular cell tumors of the tongue: fibroma or schwannoma.
AB - BACKGROUND: Granular cell tumors are benign lesions that typically occur in the
oral cavity, but can also be found in other sites. However, the characteristics
of these tumors are unclear. Thus, the present study aimed to investigate the
immunohistological characteristics of these tumors of the tongue. METHODS: Seven
patients were treated for granular cell tumors of the tongue at our institution
during 2003-2017. Paraffin-embedded specimens were available for all cases; thus,
retrospective immunohistochemical analyses were performed. RESULTS: All cases
exhibited cytoplasmic acidophilic granules in the muscle layer of the tumor. Both
the normal nerve cells and tumor cells also stained positive for PGP9.5, NSE,
calretinin, and GFAP. A nucleus of tumor cells was typically present in the
margin. The PAS-positive granules were also positive for CD68 (a lysozyme
glycoprotein marker). Various sizes of nerve fibers were observed in each tumor,
and granular cells were observed in the nerve fibers of a representative case.
CONCLUSIONS: Based on our immunohistological findings, granular cell tumors may
be derived from Schwann cells, and the presence of CD68 indicates that Wallerian
degeneration after nerve injury may be a contributor to tumor formation. Thus, a
safe surgical margin is needed to detect the infiltrative growth of granular cell
tumors.
PMID- 29329561
TI - Strongyloides stercoralis and hookworm co-infection: spatial distribution and
determinants in Preah Vihear Province, Cambodia.
AB - BACKGROUND: Strongyloides stercoralis and hookworm are two soil-transmitted
helminths (STH) that are highly prevalent in Cambodia. Strongyloides stercoralis
causes long-lasting infections and significant morbidity but is largely
neglected, while hookworm causes the highest public health burden among STH. The
two parasites have the same infection route, i.e. skin penetration. The extent of
co-distribution, which could result in potential high co-morbidities, is unknown
in highly endemic settings like Cambodia. The aim of this study was to predict
the spatial distribution of S. stercoralis-hookworm co-infection risk and to
investigate determinants of co-infection in Preah Vihear Province, North
Cambodia. METHODS: A cross-sectional survey was conducted in 2010 in 60 villages
of Preah Vihear Province. Diagnosis was performed on two stool samples, using
combined Baermann technique and Koga agar culture plate for S. stercoralis and
Kato-Katz technique for hookworm. Bayesian multinomial geostatistical models were
used to assess demographic, socioeconomic, and behavioural determinants of S.
stercoralis-hookworm co-infection and to predict co-infection risk at non
surveyed locations. RESULTS: Of the 2576 participants included in the study,
48.6% and 49.0% were infected with S. stercoralis and hookworm, respectively;
43.8% of the cases were co-infections. Females, preschool aged children, adults
aged 19-49 years, and participants who reported regularly defecating in toilets,
systematically boiling drinking water and having been treated with anthelmintic
drugs had lower odds of co-infection. While S. stercoralis infection risk did not
appear to be spatially structured, hookworm mono-infection and co-infection
exhibited spatial correlation at about 20 km. Co-infection risk was positively
associated with longer walking distances to a health centre and exhibited a small
clustering tendency. The association was only partly explained by climatic
variables, suggesting a role for underlying factors, such as living conditions
and remoteness. CONCLUSIONS: Both parasites were ubiquitous in the province, with
co-infections accounting for almost half of all cases. The high prevalence of S.
stercoralis calls for control measures. Despite several years of school-based de
worming programmes, hookworm infection levels remain high. Mebendazole efficacy,
as well as coverage of and compliance to STH control programmes should be
investigated.
PMID- 29329560
TI - Overexpression of the double homeodomain protein DUX4c interferes with
myofibrillogenesis and induces clustering of myonuclei.
AB - BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is associated with DNA
hypomethylation at the 4q35 D4Z4 repeat array. Both the causal gene DUX4 and its
homolog DUX4c are induced. DUX4c is immunodetected in every myonucleus of
proliferative cells, while DUX4 is present in only 1/1000 of myonuclei where it
initiates a gene deregulation cascade. FSHD primary myoblasts differentiate into
either atrophic or disorganized myotubes. DUX4 expression induces atrophic
myotubes and associated FSHD markers. Although DUX4 silencing normalizes the FSHD
atrophic myotube phenotype, this is not the case for the disorganized phenotype.
DUX4c overexpression increases the proliferation rate of human TE671
rhabdomyosarcoma cells and inhibits their differentiation, suggesting a normal
role during muscle differentiation. METHODS: By gain- and loss-of-function
experiments in primary human muscle cells, we studied the DUX4c impact on
proliferation, differentiation, myotube morphology, and FSHD markers. RESULTS: In
primary myoblasts, DUX4c overexpression increased the staining intensity of KI67
(a proliferation marker) in adjacent cells and delayed differentiation. In
differentiating cells, DUX4c overexpression led to the expression of some FSHD
markers including beta-catenin and to the formation of disorganized myotubes
presenting large clusters of nuclei and cytoskeletal defects. These were more
severe when DUX4c was expressed before the cytoskeleton reorganized and
myofibrils assembled. In addition, endogenous DUX4c was detected at a higher
level in FSHD myotubes presenting abnormal clusters of nuclei and cytoskeletal
disorganization. We found that the disorganized FSHD myotube phenotype could be
rescued by silencing of DUX4c, not DUX4. CONCLUSION: Excess DUX4c could disturb
cytoskeletal organization and nuclear distribution in FSHD myotubes. We suggest
that DUX4c up-regulation could contribute to DUX4 toxicity in the muscle fibers
by favoring the clustering of myonuclei and therefore facilitating DUX4 diffusion
among them. Defining DUX4c functions in the healthy skeletal muscle should help
to design new targeted FSHD therapy by DUX4 or DUX4c inhibition without
suppressing DUX4c normal function.
PMID- 29329563
TI - PM2.5-induced oxidative stress increases intercellular adhesion molecule-1
expression in lung epithelial cells through the IL-6/AKT/STAT3/NF-kappaB
dependent pathway.
AB - BACKGROUND: Epidemiological studies have shown that ambient air pollution is
closely associated with increased respiratory inflammation and decreased lung
function. Particulate matters (PMs) are major components of air pollution that
damages lung cells. However, the mechanisms remain to be elucidated. This study
examines the effects of PMs on intercellular adhesion molecule-1 (ICAM-1)
expression and the related mechanisms in vitro and in vivo. RESULT: The
cytotoxicity, reactive oxygen species (ROS) generation, and monocyte adherence to
A549 cells were more severely affected by treatment with O-PMs (organic solvent
extractable fraction of SRM1649b) than with W-PMs (water-soluble fraction of
SRM1649b). We observed a significant increase in ICAM-1 expression by O-PMs, but
not W-PMs. O-PMs also induced the phosphorylation of AKT, p65, and STAT3.
Pretreating A549 cells with N-acetyl cysteine (NAC), an antioxidant, attenuated O
PMs-induced ROS generation, the phosphorylation of the mentioned kinases, and the
expression of ICAM-1. Furthermore, an AKT inhibitor (LY294002), NF-kappaB
inhibitor (BAY11-7082), and STAT3 inhibitor (Stattic) significantly down
regulated O-PMs-induced ICAM-1 expression as well as the adhesion of U937 cells
to epithelial cells. Interleukin-6 (IL-6) was the most significantly changed
cytokine in O-PMs-treated A549 cells according to the analysis of the cytokine
antibody array. The IL-6 receptor inhibitor tocilizumab (TCZ) and small
interfering RNA for IL-6 significantly reduced ICAM-1 secretion and expression as
well as the reduction of the AKT, p65, and STAT3 phosphorylation in O-PMs-treated
A549 cells. In addition, the intratracheal instillation of PMs significantly
increased the levels of the ICAM-1 and IL-6 in lung tissues and plasma in WT
mice, but not in IL-6 knockout mice. Pre-administration of NAC attenuated those
PMs-induced adverse effects in WT mice. Furthermore, patients with chronic
obstructive pulmonary disease (COPD) had higher plasma levels of ICAM-1 and IL-6
compared to healthy subjects. CONCLUSION: These results suggest that PMs increase
ICAM-1 expression in pulmonary epithelial cells in vitro and in vivo through the
IL-6/AKT/STAT3/NF-kappaB signaling pathway.
PMID- 29329564
TI - Phytochemical analysis, antioxidant and anti-inflammatory potential of FERETIA
APODANTHERA root bark extracts.
AB - BACKGROUND: Inflammation has been implicated in many disorders, including cancer
and available therapies elicit adverse effects. Plants of the family Rubiaceae
have shown potency against inflammation. The anti-inflammatory and anti-oxidant
potential of Feretia apodanthera was investigated in this study to evaluate its
effectiveness. METHODS: The phytochemical, antioxidant and anti-inflammatory
potential of root bark (n-Hexane, diethyl ether, ethanol and aqueous) extracts of
Feretia apodanthera was investigated in this study. The extracts were subjected
to various chemical tests for phytochemical constituents; their antioxidant
activity was determined using in-vitro DPPH radical scavenging activity assay and
their anti-inflammatory activity was determined using carrageenan induced paw
oedema model. FTIR and GCMS analysis was done to determine the compounds present.
RESULTS: Phytochemical screening of extracts revealed the presence of unsaturated
steroids, triterpenes, cardiac glycosides, tannins, saponin and alkaloids.
Vitamin C had a median inhibitory concentration (IC50) of 0.038 mg/ml which was
lower than IC50 of all the extracts. Of all the extracts, ethanol extract had the
lowest IC50 (0.044 mg/ml) which is comparable to vitamin C. Anti-inflammatory
studies showed that the inflammation inhibition potential of 400 mg/kg body
weight of all the extracts was significantly lower (p < 0.05) than the standard
ketoprofen (50 mg/kg) at the first three hours but significantly higher (p <
0.05) at the fourth hour. At the fifth hour, the inflammation inhibition
potential of diethyl ether, ethanol and aqueous extracts were significantly
higher (p < 0.05) than that of the standard. FTIR analysis showed the presence of
ketones, amines, alkenes and carboxylic groups. GCMS analysis revealed compounds
that are potential anti-inflammatory agents. CONCLUSION: This study revealed that
extracts of Feretia apodanthera possess anti-inflammatory effects against right
hind paw oedema of albino rats and can act as an effective antioxidant.
PMID- 29329565
TI - Correction to: Current research into brain barriers and the delivery of
therapeutics for neurological diseases: a report on CNS barrier congress London,
UK, 2017.
AB - After publication of the article [1], it has been brought to our attention that
there are some errors in the formatting of names in the final version of the
article.
PMID- 29329566
TI - General and erosive tooth wear of 16-year-old adolescents in Kuantan, Malaysia:
prevalence and association with dental caries.
AB - BACKGROUND: The objective of this study was to determine the prevalence and
severity of general tooth wear (GTW), i.e. tooth wear irrespective of etiology
and erosive tooth wear (ETW), i.e. tooth wear predominantly due to erosion; and
also to investigate the relationship between ETW and dental caries experience in
16-year-old adolescents in Kuantan, Malaysia. METHODS: A multi-staged cluster
sampling method was employed. A total of 598 16-year-old adolescents participated
in this study. Participants' demographic profile was assessed through a self
administered questionnaire. Clinical examinations were carried out under
standardized conditions by a single examiner. The level of GTW was recorded using
the modified Smith and Knight's Tooth Wear Index (TWI) whilst ETW were recorded
using the Basic Erosive Wear Examination (BEWE) index. This index was developed
to record clinical findings and assist in the decision-making process for the
management of erosive tooth wear. Dental caries was recorded using the D3MFT
index whereby D3 denotes obvious dental decay into dentine detected visually.
RESULTS: The prevalence of GTW, ETW and dental caries, i.e. percentage of
individuals found to have at least one lesion, was 99.8%, 45.0% and 27.8%
respectively. Two thirds of affected teeth with GTW were observed to have a TWI
score of 1 whereas almost all of the affected teeth with ETW had a BEWE score of
2. The mean D3MFT was 0.62 (95% CI 0.50, 0.73) with Decayed (D) teeth being the
largest component, mean D3T was 0.36 (95% CI 0.30, 0.43). There was no
significant association between socio-demographic factors and prevalence of ETW.
Logistic regression analysis also showed no significant relationship between the
prevalence of ETW and D3MFT (p > 0.05). CONCLUSIONS: Almost all adolescents
examined had GTW but they were mainly early lesions. However, nearly half were
found to have ETW of moderate severity (BEWE score 2). No significant
relationship between the occurrence of erosive tooth wear and caries was observed
in this population.
PMID- 29329567
TI - Modified Pilates as an adjunct to standard physiotherapy care for urinary
incontinence: a mixed methods pilot for a randomised controlled trial.
AB - BACKGROUND: Urinary incontinence (UI) is a distressing condition affecting at
least 5 million women in England and Wales. Traditionally, physiotherapy for UI
comprises pelvic floor muscle training, but although evidence suggests this can
be effective it is also recognised that benefits are often compromised by patient
motivation and commitment. In addition, there is increasing recognition that
physical symptoms alone are poor indicators of the impact of incontinence on
individuals' lives. Consequently, more holistic approaches to the treatment of
UI, such as Modified Pilates (MP) have been recommended. This study aimed to
provide preliminary findings about the effectiveness of a 6-week course of MP
classes as an adjunct to standard physiotherapy care for UI, and to test the
feasibility of a randomised controlled trial (RCT) design. METHODS: The study
design was a single centre pilot RCT, plus qualitative interviews. 73 women
referred to Women's Health Physiotherapy Services for UI at Colchester Hospital
University NHS Foundation Trust were randomly assigned to two groups: a 6-week
course of MP classes in addition to standard physiotherapy care (intervention) or
standard physiotherapy care only (control). Main outcome measures were self
reported UI, quality of life and self-esteem at baseline (T1), completion of
treatment (T2), and 5 months after randomisation (T3). Qualitative interviews
were conducted with a subgroup at T2 and T3. Due to the nature of the
intervention blinding of participants, physiotherapists and researchers was not
feasible. RESULTS: Post-intervention data revealed a range of benefits for women
who attended MP classes and who had lower symptom severity at baseline: improved
self-esteem (p = 0.032), decreased social embarrassment (p = 0.026) and lower
impact on normal daily activities (p = 0.025). In contrast, women with higher
symptom severity showed improvement in their personal relationships (p = 0.017).
Qualitative analysis supported these findings and also indicated that MP classes
could positively influence attitudes to exercise, diet and wellbeing.
CONCLUSIONS: A definitive RCT is feasible but will require a large sample size to
inform clinical practice. TRIAL REGISTRATION: ISRCTN74075972 Registered 12/12/12
(Retrospectively registered).
PMID- 29329568
TI - Prospective longitudinal quality of life and survival outcomes in patients with
advanced infiltrative hepatocellular carcinoma and portal vein thrombosis treated
with Yttrium-90 radioembolization.
AB - BACKGROUND: To determine the effect of Yttrium-90 (Y90) radioembolization on
health-related quality of life (HRQOL) and its effect on overall survival
advanced, unresectable infiltrative hepatocellular carcinoma (HCC) patients with
concurrent portal vein thrombosis (PVT). METHODS: Consecutive patients with
unresectable infiltrative HCC and PVT were recruited. The Short-Form 36 (SF-36)
questionnaire was used to assess HRQOL for consecutive patients treated with
glass-based Y90 based on a prospective phase II trial. MR imaging was used to
determine tumor progression every 3 months post-treatment. Overall survival (OS)
from treatment and time to progression (TTP) was analyzed using Kaplan-Meier
estimation and log-rank test. RESULTS: Thirty patients were treated and followed
for 17.4 months; physical and mental component summary scores (PCS & MCS)
remained unchanged at one, three, and six months. While no difference was
observed in baseline SF-36 scores for patients with prolonged TTP (>=4 months)
and OS (>= 6 months), corresponding 1-month PCS were significantly higher than
those with TTP < 4 months and OS < 6 months. At 1 month, patients with normalized
Physical Function (PF), Role Physical (RP) and PCS within 2 standard deviations
(SD) of US normalized baseline scores had a significantly prolonged median OS
(15.7 vs. 3.7 months; p < 0.001) and TTP (12.4 vs. 1.8 mo; p < 0.001) compared
those with physical component scores greater than 2SD below normalized US
population values. CONCLUSION: Y90 radioembolization for HCC demonstrated long
term preservation of HRQOL. Lower baseline HRQOL scores were predictive of poorer
OS. Early (1 month post-treatment) significant decreases in PCS were independent
predictors of poorer OS and TTP. TRIAL REGISTRATION: ClinicalTrials.gov
identifier NCT01556282 , registered March 16, 2012.
PMID- 29329569
TI - Effect of total number of harvested lymph nodes on survival outcomes after
curative resection for gastric adenocarcinoma: findings from an eastern high
volume gastric cancer center.
AB - BACKGROUND: Greater lymph node retrieval in gastric cancer improves staging
accuracy and may improve survival from increased clearance of nodal
micrometastasis. This retrospective cohort study investigated if more lymph nodes
removed in gastric cancer increases survival and if such effect is stage-specific
due to differential risks of nodal micrometastasis and systemic disease. METHODS:
The prospectively collected database of curatively resected gastric cancer
patients in National Cancer Center, South Korea between 2000 and 2009 was
reviewed. Disease-free survival (DFS) and overall survival (OS) for all patients
and for each stage according to number of lymph nodes examined (1-30, 31-45, >
45) were analyzed. RESULTS: Of 4049 patients, 96.6% and 98.4% underwent D2
(perigastric and extragastric) lymphadenectomy and had >= 15 lymph nodes
examined. Mean number of nodes examined was 43. Five-year OS & DFS rates were
83.3% and 80.7%. Patients with > 45 nodes examined had significantly lower DFS (p
= 0.002) and OS (p = 0.007) compared to those with 1-30 and 31-45 nodes. However,
proportion of patients with > 45 nodes examined increased with stage (p =
0.0005). Per stage, there was no significant difference in DFS and OS according
to number of nodes examined except for stage IIIA favoring more nodes (p = 0.018
and p = 0.044, respectively). Similar trend was seen in stage IIB. Number of
examined nodes positively correlated with number of pathologic nodes for all
patients (r = 0.144, p < .001) but not for stage IIB and IIIA. Number of nodes
examined was a significant survival predictor in stage IIIA. CONCLUSION: Greater
lymph node harvest showed improved survival in intermediate-stage gastric cancer.
PMID- 29329570
TI - Exophthalmos in a young woman with no graves' disease - a case report of IgG4
related orbitopathy.
AB - BACKGROUND: Immunoglobulin G4-related disease (IgG4-rd) is characterized by
lymphoplasmacytic infiltration and tissue fibrosis. Orbital manifestations of
IgG4-rd may include unilateral or bilateral proptosis, cicatricial extraocular
muscle myopathy, orbital inflammation and pain which may mimic ophthalmic Graves'
disease. CASE PRESENTATION: A 25-year-old woman has been referred to the
endocrinology clinic, 4 months after delivery, with suspected Graves'
orbitopathy. She has had bronchial asthma and recurrent skin rashes of unknown
aetiology for the last 10 years and was treated for dacryoadenitis with steroid
containing eye drops 5 years ago. During pregnancy she developed eyelid swelling.
After delivery, eyelid redness and retrobulbar pain evolved. Proptosis was
demonstrated by Hertel's exophthalmometry. Orbital magnetic resonance imaging
showed enlarged lateral and superior rectus muscles in both orbits. Thyroid
function tests were in the normal range and no thyroid stimulating hormone (TSH)
receptor autoantibodies were present. The eye muscle involvement pattern raised
suspicion, and the high IgG4 level with positive histology of the lacrimal gland
confirmed the diagnosis of immunoglobulin G4-related orbitopathy. Rapid
improvement was observed following oral methylprednisolone. CONCLUSIONS: IgG4
related orbitopathy may mimic Graves' orbitopathy. Euthyroid patients with no TSH
receptor autoantibodies should be evaluated for immunoglobulin G4-related
orbitopathy. Once IgG4-related orbitopathy is proven, other manifestations of
IgG4-related disease have to be searched for; lifelong follow-up is warranted.
PMID- 29329571
TI - Environmental exposures and fetal growth: the Haifa pregnancy cohort study.
AB - BACKGROUND: The developing fetus is susceptible to environmental insults.
Studying the effects of environmental exposures on fetal growth is essential for
understanding the causal pathway between prenatal exposures and pregnancy
outcomes. Here we describe the Haifa Pregnancy Cohort Study (HPCS) and discuss
challenges and opportunities in applying "big data" paradigm. METHODS: Maccabi
Healthcare Services (MHS), is the second largest Israeli health maintenance
organization (HMO) providing care services to two million beneficiaries. The HPCS
cohort potentially includes ~750,000 newborns born between 1998 and 2017. We will
estimate daily exposures to air pollutants, temperature and greenness, using
satellite-based data and models. We hypothesize that residents of Haifa have
higher exposures to environmental pollutants and that in pregnant women this
higher exposure is associated with poorer fetal growth. We will evaluate outcomes
such as birth-weight, head-circumference and gestational age at birth. We will
adjust for pregnancy complications such as pre-eclampsia and gestational diabetes
and parental variables, such as maternal weight, age and smoking habits as
potential confounders. In addition, we will conduct a multi-tiered field study,
nested within this population, among 150 pregnant women residing in two
geographical regions-one in the polluted Haifa area, and one in a relatively
unpolluted area in central Israel. Blood and urinary samples will be collected,
as well as personal and indoor exposure to air pollution. DISCUSSION: Evaluating
environmental exposures of pregnant women and assessing in utero growth over the
course of the pregnancy during different exposure windows, is of great scientific
and public health interest. Recent advances in data collection and analysis pose
great promise to provide insights into contribution of environment to the health
of the developing fetus, but also pose major challenges and pitfalls, such as
data management, proper statistical framework and integration of data in the
population-based study and selectiveness in the nested field study. Yet the
continuing follow-up of the study cohort, integrating data from different
services, health-promotion, and eventually, application later in real life of our
main promises. Our study aims to meet these challenges and to provide evidence of
the environmental exposures associated with fetal growth.
PMID- 29329572
TI - Socio-demographic and lifestyle determinants of dietary patterns in French
speaking Switzerland, 2009-2012.
AB - BACKGROUND: Food intake is a complex behaviour which can be assessed using
dietary patterns. Our aim was to characterize dietary patterns and associated
factors in French-speaking Switzerland. METHODS: Cross-sectional study conducted
between 2009 and 2012 in the city of Lausanne, Switzerland, including 4372
participants (54% women, 57.3 +/- 10.3 years). Food consumption was assessed
using a validated food frequency questionnaire. Dietary patterns were assessed by
principal components analysis. RESULTS: Three patterns were identified: "Meat &
fries"; "Fruits & Vegetables" and "Fatty & sugary". The "Meat & fries" pattern
showed the strongest correlations with total and animal protein and cholesterol
carbohydrates, dietary fibre and calcium. The "Fruits & Vegetables" pattern
showed the strongest correlations with dietary fibre, carotene and vitamin D. The
"Fatty & sugary" pattern showed the strongest correlations with total energy and
saturated fat. On multivariate analysis, male gender, low educational level and
sedentary status were positively associated with the "Meat & fries" and the
"Fatty & sugary" patterns, and negatively associated with the "Fruits &
Vegetables" pattern. Increasing age was inversely associated with the "Meat &
fries" pattern; smoking status was inversely associated with the "Fruits &
Vegetables" pattern. Being born in Portugal or Spain was positively associated
with the "Meat & fries" and the "Fruits & Vegetables" patterns. Increasing body
mass index was positively associated with the "Meat & fries" pattern and
inversely associated with the "Fatty & sugary" pattern. CONCLUSIONS: Three
dietary patterns, one healthy and two unhealthy, were identified in the Swiss
population. Several associated modifiable behaviours were identified; the
information on socio- demographic determinants allows targeting of the most
vulnerable groups in the context of public health interventions.
PMID- 29329573
TI - Female genital mutilation/cutting in Italy: an enhanced estimation for first
generation migrant women based on 2016 survey data.
AB - BACKGROUND: Migration flows of women from Female Genital Mutilation/Cutting
practicing countries have generated a need for data on women potentially affected
by Female Genital Mutilation/Cutting. This paper presents enhanced estimates for
foreign-born women and asylum seekers in Italy in 2016, with the aim of
supporting resource planning and policy making, and advancing the methodological
debate on estimation methods. METHODS: The estimates build on the most recent
methodological development in Female Genital Mutilation/Cutting direct and
indirect estimation for Female Genital Mutilation/Cutting non-practicing
countries. Direct estimation of prevalence was performed for 9 communities using
the results of the survey FGM-Prev, held in Italy in 2016. Prevalence for
communities not involved in the FGM-Prev survey was estimated using to the
'extrapolation-of-FGM/C countries prevalence data method' with corrections
according to the selection hypothesis. RESULTS: It is estimated that 60 to 80
thousand foreign-born women aged 15 and over with Female Genital
Mutilation/Cutting are present in Italy in 2016. We also estimated the presence
of around 11 to 13 thousand cut women aged 15 and over among asylum seekers to
Italy in 2014-2016. Due to the long established presence of female migrants from
some practicing communities Female Genital Mutilation/Cutting is emerging as an
issue also among women aged 60 and over from selected communities. Female Genital
Mutilation/Cutting is an additional source of concern for slightly more than 60%
of women seeking asylum. CONCLUSIONS: Reliable estimates on Female Genital
Mutilation/Cutting at country level are important for evidence-based policy
making and service planning. This study suggests that indirect estimations cannot
fully replace direct estimations, even if corrections for migrant socioeconomic
selection can be implemented to reduce the bias.
PMID- 29329574
TI - Microcephaly epidemic related to the Zika virus and living conditions in Recife,
Northeast Brazil.
AB - BACKGROUND: Starting in August 2015, there was an increase in the number of cases
of neonatal microcephaly in Northeast Brazil. These findings were identified as
being an epidemic of microcephaly related to Zika virus (ZIKV) infection. The
present study aims to analyse the spatial distribution of microcephaly cases in
Recife (2015-2016), which is in Northeast Brazil, and its association with the
living conditions in this city. METHODS: This was an ecological study that used
data from reported cases of microcephaly from the State Health Department of
Pernambuco (August 2015 to July 2016). The basic spatial unit of analysis was the
94 districts of Recife. The case definition of microcephaly was: neonates with a
head circumference of less than the cut-off point of -2 standard deviations below
the mean value from the established Fenton growth curve. As an indicator of the
living conditions of the 94 districts, the percentage of heads of households with
an income of less than twice the minimum wage was calculated. The districts were
classified into four homogeneous strata using the K-means clustering algorithm.
We plotted the locations of each microcephaly case over a layer of living
conditions. RESULTS: During the study period, 347 microcephaly cases were
reported, of which 142 (40.9%) fulfilled the definition of a microcephaly case.
Stratification of the 94 districts resulted in the identification of four strata.
The highest stratum in relation to the living conditions presented the lowest
prevalence rate of microcephaly, and the overall difference between this rate and
the rates of the other strata was statistically significant. The results of the
Kruskal-Wallis test demonstrated that there was a strong association between a
higher prevalence of microcephaly and poor living conditions. After the first 6
months of the study period, there were no microcephaly cases recorded within the
population living in the richest socio-economic strata. CONCLUSION: This study
showed that those residing in areas with precarious living conditions had a
higher prevalence of microcephaly compared with populations with better living
conditions.
PMID- 29329575
TI - MicroRNA-200a confers chemoresistance by antagonizing TP53INP1 and YAP1 in human
breast cancer.
AB - BACKGROUND: Emerging evidence suggests molecular and phenotypic association
between treatment resistance and epithelial-mesenchymal transition (EMT) in
cancer. Compared with the well-defined molecular events of miR-200a in EMT, the
role of miR-200a in therapy resistance remains to be elucidated. METHODS: Breast
cancer cells transfected with mimic or inhibitor for miR-200a was assayed for
chemoresistance in vitro. miR-200a expression was assessed by quantitative real
time PCR (qRT-PCR) in breast cancer patients treated with preoperative
chemotherapy. Luciferase assays, cell proliferation assay were performed to
identify the targets of miR-200a and the mechanism by which it promotes treatment
resistance. Survival analysis was used to evaluate the prognosis value of miR
200a. RESULTS: In this study, our results showed ectopic expression of miR-200a
promotes chemoresistance in breast cancer cell lines to several chemotherapeutic
agents, whereas inhibition of miR-200a enhances gemcitabine chemosensitivity in
resistance cancer cells. We found overexpression of miR-200a was closely
associated with poor response to preoperative chemotherapy and poor prognosis in
breast cancer patients. Furthermore, knockdown of YAP1 and TP53INP1 phenocopied
the effects of miR-200a overexpression, and confirmed that TP53INP1 is a novel
target of miR-200a. Remarkably, TP53INP1 expression is inversely correlated with
miR-200a expression in Breast cancer cell lines. Taken together, these clinical
and experimental results demonstrate that miR-200a is a determinant of
chemoresistance of breast cancer. CONCLUSIONS: Upregulated miR-200a enhances
treatment resistance via antagonizing TP53INP1 and YAP1 in breast cancer.
PMID- 29329576
TI - Spontaneous prematurity in fetuses with congenital diaphragmatic hernia: a
retrospective cohort study about prenatal predictive factors.
AB - BACKGROUND: To evaluate possible predictive factors of spontaneous prematurity in
fetuses with congenital diaphragmatic hernia (CDH). METHODS: A retrospective
cohort study was performed. Inclusion criteria were presence of CDH; absence of
fetoscopy; absence of karyotype abnormality; maximum of one major malformation
associated with diaphragmatic hernia; ultrasound monitoring at the Obstetrics
Clinic of Clinicas Hospital at the University of Sao Paulo School of Medicine,
from January 2001 to October 2014. The data were obtained through the electronic
records and ultrasound system of our fetal medicine service. The following
variables were analyzed: maternal age, primiparity, associated maternal diseases,
smoking, previous spontaneous preterm birth, fetal malformation associated with
hernia, polyhydramnios, fetal growth restriction, presence of intrathoracic
liver, invasive procedures performed, side of hernia and observed-to- expected
lung to head ratio (o/e LHR). On individual analysis, variables were assessed
using the Chi-square test and the Mann-Whitney test. A multiple logistic
regression model was applied to select variables independently influencing the
prediction of preterm delivery. A ROC curve was constructed with the significant
variable, identifying the values with best sensitivity and specificity to be
suggested for use in clinical practice. RESULTS: Eighty fetuses were evaluated,
of which, 21 (26.25%) were premature. O/e LHR was the only factor associated with
prematurity (p = 0.020). The ROC curve showed 93% sensitivity with 48.4%
specificity for the cutoff of 40%. CONCLUSION: O/e LHR was the only predictor of
prematurity in this sample.
PMID- 29329577
TI - Respiratory explants as a model to investigate early events of contagious bovine
pleuropneumonia infection.
AB - Contagious bovine pleuropneumonia (CBPP) is a severe disease caused by Mycoplasma
mycoides subsp. mycoides (Mmm). Knowledge on CBPP pathogenesis is fragmented and
hampered by the limited availability of laboratory animal and in vitro models of
investigation. The purpose of the present study is to assess respiratory explants
as useful tools to study the early stages of CBPP. Explants were obtained from
trachea, bronchi and lungs of slaughtered cattle, tested negative for Mycoplasma
spp. and for the major bacterial and viral respiratory pathogens. The interaction
of Mmm with explant cells was studied by immunohistochemistry (IHC), double
labelling indirect immunofluorescence (DLIIF) and laser scanning confocal
microscopy (LSCM). Mmm capability to survive and proliferate within the explants
was evaluated by standard microbiological procedures. Finally, the putative
cellular internalization of Mmm was further investigated by the gentamicin
invasion assay. IHC and DLIIF indicated that Mmm can colonize explants, showing a
marked tropism for lower airways. Specifically, Mmm was detected on/inside the
bronchiolar and alveolar epithelial cells, the alveolar macrophages and the
endothelial cells. The interaction between Mmm and explant cells was abolished by
the pre-incubation of the pathogen with bovine anti-Mmm immune sera. Mmm was able
to survive and proliferate in all tracheal, bronchial and lung explants, during
the entire time course of the experiments. LSCM and gentamicin invasion assay
both confirmed that Mmm can enter non-phagocytic host cells. Taken together, our
data supports bovine respiratory explants as a promising tool to investigate
CBPP, alternative to cattle experimental infection.
PMID- 29329578
TI - Guideline-based quality indicators-a systematic comparison of German and
international clinical practice guidelines: protocol for a systematic review.
AB - BACKGROUND: Quality indicators (QIs) are used in assessing the quality of
healthcare. Evidence-based clinical practice guidelines (CPGs) are relevant
sources for generating QIs. In this context, QIs are important tools to assess
the implementation of guideline recommendations. However, the methodological
approaches to guideline-based QI development vary considerably. In Germany, the
guideline classification scheme of the AWMF (German Association of the Scientific
Medical Societies) differentiates between S1-, S2k-, S2e-, and S3-CPGs depending
on the methodological approach. Thus, S3-CPGs are consensus- and evidence-based
CPGs and have the highest methodological standard in Germany. An analysis of the
status quo of reported QIs in S3-CPGs found 35 current S3-CPGs, which report 372
different QIs. Currently, there is no gold standard for the development of
guideline-based QIs. To our knowledge, no studies have investigated to what
extent guideline-based QIs from different CPGs that are related to the same topic
are consistent. The objective of this study is to compare guideline-based QIs and
their underlying methodological approaches of German S3-CPGs with those of topic
related international CPGs. METHODS: Based on the previous identified German S3
CPGs (n = 35), which report quality indicators, we will conduct systematic
searches in the guidelines databases of G-I-N (Guidelines International Network)
and NGC (National Guideline Clearinghouse) to identify international CPGs
matching the topics of the S3-CPGs. If necessary, we will search additionally the
websites of the particular CPG providers for separate documents with regard to
QIs. We will include evidence-based CPGs which report QIs. Reported QIs as well
as methods of development and the rationale for QIs will be extracted and
compared with those of the S3-CPGs. DISCUSSION: This study will be part of the
project "Systematic analysis of the translation of guideline recommendations into
quality indicators and development of an evidence- and consensus-based standard,"
supported by the German Research Association (DFG). The results of this analysis
will feed into a subsequent qualitative study, which will consist of structured
interviews with developers of international CPGs. Further, the results will be
considered in a consensus study on standards of the translation of guideline
recommendations into quality indicators in Germany.
PMID- 29329579
TI - Prevalence and incidence of major depressive disorders among people living with
HIV residing in Africa: a systematic review and meta-analysis protocol.
AB - BACKGROUND: Depression represents one of the most frequent neuro-psychiatric
diseases; it seems to be more prevalent in people living with HIV compared to the
general population. However, summarized data in the African setting on the topic
are scarce. This systematic review and meta-analysis aims at assessing the
prevalence and incidence of major depressive disorders (MDD) in HIV-infected
African populations residing in Africa. METHODS AND DESIGN: This review will
include observational studies conducted among HIV-infected people residing in
Africa, which have reported either the prevalence or incidence of MDD or enough
data for its appraisal. Relevant records will be searched using PubMed/Medline,
EMBASE, African Journals Online, and Africa Index Medicus. In addition, reference
lists of eligible papers and relevant review articles will be screened. Published
studies from inception Jan 1, 2000 to Dec 31, 2017 will be considered regardless
of language of publication. Two review authors will independently screen, select
studies, and extract data, with discrepancies resolved by consensus or
arbitration by a third review author. Methodological quality of included studies
will be assessed using the scale developed by Hoy and colleagues. Funnel-plots
and Egger's test will be used to determine publication bias. The study-specific
estimates will be pooled through a random-effects meta-analysis model to obtain
an overall summary estimate. The heterogeneity will be evaluated by the chi2 test
on Cochrane's Q statistic. Results will be presented by geographical region and
antiretroviral therapy status. DISCUSSION: This study is based on published data;
therefore, ethical approval is not a requirement. The final report of this study
in the form of a scientific paper will be published in a peer-reviewed journal
and presented at scientific conferences. This review will help to have an
overview of the burden of MDD among HIV-infected people residing in Africa.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42017058118 .
PMID- 29329580
TI - Evidence for the activation of pyroptotic and apoptotic pathways in RPE cells
associated with NLRP3 inflammasome in the rodent eye.
AB - BACKGROUND: Age-related macular degeneration (AMD) is a devastating eye disease
causing irreversible vision loss in the elderly. Retinal pigment epithelium
(RPE), the primary cell type that is afflicted in AMD, undergoes programmed cell
death in the late stages of the disease. However, the exact mechanisms for RPE
degeneration in AMD are still unresolved. The prevailing theories consider that
each cell death pathway works independently and without regulation of each other.
Building upon our previous work in which we induced a short burst of inflammasome
activity in vivo, we now investigate the effects of prolonged inflammasome
activity on RPE cell death mechanisms in rats. METHODS: Long-Evans rats received
three intravitreal injections of amyloid beta (Abeta), once every 4 days, and
were sacrificed at day 14. The vitreous samples were collected to assess the
levels of secreted cytokines. The inflammasome activity was evaluated by both
immunohistochemistry and western blot. The types of RPE cell death mechanisms
were determined using specific cell death markers and morphological
characterizations. RESULTS: We found robust inflammasome activation evident by
enhanced caspase-1 immunoreactivity, augmented NF-kappaB nuclear
translocalization, increased IL-1beta vitreal secretion, and IL-18 protein
levels. Moreover, we observed elevated proteolytic cleavage of caspase-3 and
gasdermin D, markers for apoptosis and pyroptosis, respectively, in RPE-choroid
tissues. There was also a significant reduction in the anti-apoptotic factor, X
linked inhibitor of apoptosis protein, consistent with the overall changes of RPE
cells. Morphological analysis showed phenotypic characteristics of pyroptosis
including RPE cell swelling. CONCLUSIONS: Our data suggest that two cell death
pathways, pyroptosis and apoptosis, were activated in RPE cells after exposure to
prolonged inflammasome activation, induced by a drusen component, Abeta. The
involvement of two distinct cell death pathways in RPE sheds light on the
potential interplay between these pathways and provides insights on the future
development of therapeutic strategies for AMD.
PMID- 29329581
TI - MicroRNA-124 regulates the expression of MEKK3 in the inflammatory pathogenesis
of Parkinson's disease.
AB - BACKGROUND: Parkinson's disease (PD) is the most prevalent neurodegenerative
disorder that is characterised by selective loss of midbrain dopaminergic (DA)
neurons. Chronic inflammation of the central nervous system is mediated by
microglial cells and plays a critical role in the pathological progression of PD.
Brain-specific microRNA-124 (miR-124) expression is significantly downregulated
in lipopolysaccharide (LPS)-treated BV2 cells and in the 1-methyl-4-phenyl
1,2,3,6-tetrahydropyridine (MPTP) model of PD. However, whether abnormal miR-124
expression could regulate the activation of microglia remains poorly understood.
METHODS: BV2 cells were activated by exposure to LPS, and the expression levels
of miR-124, mitogen-activated protein kinase kinase kinase 3 (MEKK3), and the
nuclear factor of kappaB (NF-kappaB) p-p65 were analysed. Over-expression and
knockdown studies of miR-124 were performed to observe the effects on MEKK3/NF
kappaB signalling pathways, and the induction of pro-inflammatory and neurotoxic
factors was assessed. In addition, a luciferase reporter assay was conducted to
confirm whether MEKK3 is a direct target of miR-124. Meanwhile, production of miR
124, MEKK3, and p-p65; midbrain DA neuronal death; or activation of microglia
were analysed when treated with or without miR-124 in the MPTP-induced model of
PD. RESULTS: We found that the knockdown of MEKK3 could inhibit the activation of
microglia by regulating NF-kappaB expression. Over-expression of miR-124 could
effectively attenuate the LPS-induced expression of pro-inflammatory cytokines
and promote the secretion of neuroprotective factors. We also first identified a
unique role of miR-124 in mediating the microglial inflammatory response by
targeting MEKK3/NF-kappaB signalling pathways. In the microglial culture
supernatant (MCS) transfer model, over-expression of the miR-124 or knockdown of
MEKK3 in BV2 cells prevented SH-SY5Y from apoptosis and death. Moreover, MEKK3
and p-p65 were abundantly expressed in the midbrain. Furthermore, their
expression levels increased and microglial activation was observed in the MPTP
induced model of PD. In addition, exogenous delivery of miR-124 could suppress
MEKK3 and p-p65 expression and attenuate the activation of microglia in the
substantia nigra pars compacta of MPTP-treated mice. miR-124 also could prevent
MPTP-dependent apoptotic midbrain DA cell death in a MPTP-induced PD model.
CONCLUSIONS: Taken together, our data suggest that miR-124 can inhibit
neuroinflammation in the development of PD by regulating the MEKK3/NF-kappaB
signalling pathways and implicate miR-124 as a potential therapeutic target for
regulating the inflammatory response in PD.
PMID- 29329582
TI - When do patient reported quality of life indicators become prognostic in breast
cancer?
AB - BACKGROUND: Various patient reported quality-of-life indicators are independently
prognostic for survival in metastatic breast cancer and other cancers. The same
measures recorded at first diagnosis of early breast cancer carry no
corresponding prognostic information. The present study aims to assess at what
time in the disease evolution the prognostic association appears. METHODS: Among
8024 patients enrolled in one of seven randomized controlled trials in early
stage breast cancer 3247 had a breast cancer relapse after a median follow-up of
12.1 years. Of these 677 had completed QL indicator assessments within defined
windows 1, 2 or 3 months prior to relapse. We performed Cox regression analyses
using these assessments and using identical instruments after relapse. All
analyses were stratified by trial and adjusted for baseline clinicopathologic
factors. RESULTS: QL indicators in the months before relapse were not
significantly prognostic for subsequent survival with the possibly chance
exception of mood at the second month before relapse. After relapse, physical
well-being was statistically significantly associated with survival (P < 0.001).
This prognostic significance increased in later post-relapse assessments. Similar
findings were observed using patient-reported indicators for nausea and vomiting,
appetite, coping effort, and health perception. CONCLUSIONS: Before cancer
relapse, QL indicators were not generally prognostic for subsequent survival.
After relapse, QL indicators substantially predicted OS, with a stronger
association later in the course of relapsed disease. Simple patient perception of
disease burden seems unlikely to explain this sudden change: rather the patient's
awareness of disease relapse must contribute.
PMID- 29329583
TI - Correction to: Dendrimer-mediated delivery of N-acetyl cysteine to microglia in a
mouse model of Rett syndrome.
AB - After publication of the article [1], it has been brought to our attention that
an author's name has been formatted incorrectly.
PMID- 29329584
TI - Validity of the school setting interview for students with special educational
needs in regular high school - a Rasch analysis.
AB - BACKGROUND: Participation in education is a vital component of adolescents'
everyday life and a determinant of health and future opportunities in adult life.
The School Setting Interview (SSI) is an instrument which assesses student
environment fit and reflects the potential needs for adjustments to enhance
students' participation in school activities. The aim of the study was to
investigate the psychometric properties of the SSI for students with special
educational needs in regular high school. METHODS: A sample of 509 students with
special educational needs was assessed with the SSI. The polytomous unrestricted
Rasch model was used to analyze the psychometric properties of the SSI regarding
targeting, model fit, differential item functioning (DIF), response category
functioning and unidimensionality. RESULTS: The SSI generally confirmed fit to
assumptions of the Rasch model. Reliability was acceptable (0.73) and the SSI
scale was able to separate students into three different levels of student
environment fit. DIF among gender was detected in item "Remember things" and in
item "Homework" DIF was detected among students with or without diagnosis. All
items had disordered thresholds. The SSI demonstrated unidimensionality and no
response dependence was present among items. CONCLUSION: The results suggest that
the SSI is valid for use among students with special educational needs in order
to provide and evaluate environmental adjustments. However, the items with the
detected DIF and the SSI rating scale with its disordered thresholds needs to be
further scrutinized.
PMID- 29329585
TI - Involvement of hedgehog pathway in early onset, aggressive molecular subtypes and
metastatic potential of breast cancer.
AB - BACKGROUND: Dysregulation of hedgehog pathway is observed in numerous cancers.
Relevance of hedgehog pathway genes in cancer cohort and inhibition of its
downstream effector (GLI1) towards metastasis in cell lines are explored in the
study. METHOD: One hundred fifty fresh tumours of breast cancer patients were
collected for the study. Based on differential expression, panel of 6 key
regulators of the pathway (SHH, DHH, IHH, PTCH1, SMO and GLI1) in microarray
datasets were identified. Expressional profiles of aforementioned genes were
later correlated with clinico-pathological parameters in Pakistani breast cancer
cohort at transcript and protein levels. In addition, GLI1 over expressing breast
cancer cell lines (MDA-MB-231 and MCF-7) were treated with GANT61 to explore its
probable effects on metastasis. RESULT: SHH, DHH, PTCH1 and GLI1 were
significantly over-expressed in tumours as compared with respective normal
mammary tissues. A significant correlation of SHH, DHH and GLI1 expression with
advanced tumour size, stages, grades, nodal involvement and distant metastasis
was observed (p < 0.05). Over-expression of SHH, DHH and GLI1 was significantly
related with patients having early onset and pre-menopausal status. Of note,
hedgehog pathway was frequently up regulated in luminal B and triple negative
breast cancer affected women. In addition, positive correlations were observed
among aforementioned members of pathway and Ki67 (r-value: 0.63-0.78) emphasizing
their role towards disease progression. Exposure of GANT61 (inhibitor for GLI1)
significantly restricted cell proliferation, reduced cell motility and invasion.
CONCLUSION: Role of activated hedgehog pathway in breast cancer metastasis
provides a novel target for cancer therapy against aggressive cancer subtypes.
PMID- 29329586
TI - IL-33/ST2 signaling contributes to radicular pain by modulating MAPK and NF
kappaB activation and inflammatory mediator expression in the spinal cord in rat
models of noncompressive lumber disk herniation.
AB - BACKGROUND: Immune and inflammatory responses occurring in the spinal cord play a
pivotal role in the progression of radicular pain caused by intervertebral disk
herniation. Interleukin-33 (IL-33) orchestrates inflammatory responses in a wide
range of inflammatory and autoimmune disorders of the nervous system. Thus, the
purpose of this study is to investigate the expression of IL-33 and its receptor
ST2 in the dorsal spinal cord and to elucidate whether the inhibition of spinal
IL-33 expression significantly attenuates pain-related behaviors in rat models of
noncompressive lumbar disc herniation. METHODS: Lentiviral vectors encoding short
hairpin RNAs that target IL-33 (LV-shIL-33) were constructed for gene silencing.
Rat models of noncompressive lumber disk herniation were established, and the
spines of rats were injected with LV-shIL-33 (5 or 10 MUl) on the first day after
the operation. Mechanical thresholds were evaluated during an observation period
of 21 days. Moreover, the expression levels of spinal tumor necrosis factor-alpha
(TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and
cyclooxygenase 2 (COX-2) and the activation of the mitogen-activated protein
kinases (MAPK) and nuclear factor-kappaB (NF-kappaB) pathways were evaluated to
gain insight into the mechanisms related to the contribution of IL-33/ST2
signaling to radicular pain. RESULTS: The application of nucleus pulposus (NP) to
the dorsal root ganglion (DRG) induced an increase in IL-33 and ST2 expression in
the spinal cord, mainly in the dorsal horn neurons, astrocytes, and
oligodendrocytes. Spinally delivered LV-shIL-33 knocked down the expression of IL
33 and markedly attenuated mechanical allodynia. In addition, spinal
administration of LV-shIL-33 reduced the overexpression of spinal IL-1beta, TNF
alpha, and COX-2 and attenuated the activation of C-Jun N-terminal kinase (JNK),
extracellular signal-regulated kinase (ERK), and NF-kappaB/p65 but not p38.
CONCLUSIONS: This study indicates that spinal IL-33/ST2 signaling plays an
important role in the development and progression of radicular pain in rat models
of noncompressive lumber disk herniation. Thus, the inhibition of spinal IL-33
expression may provide a potential treatment to manage radicular pain caused by
intervertebral disk herniation.
PMID- 29329587
TI - The effectiveness of a web 2.0 physical activity intervention in older adults - a
randomised controlled trial.
AB - BACKGROUND: Interactive web-based physical activity interventions using Web 2.0
features (e.g., social networking) have the potential to improve engagement and
effectiveness compared to static Web 1.0 interventions. However, older adults may
engage with Web 2.0 interventions differently than younger adults. The aims of
this study were to determine whether an interaction between intervention (Web 2.0
and Web 1.0) and age group (<55y and >=55y) exists for website usage and to
determine whether an interaction between intervention (Web 2.0, Web 1.0 and
logbook) and age group (<55y and >=55y) exists for intervention effectiveness
(changes in physical activity). METHODS: As part of the WALK 2.0 trial, 504
Australian adults were randomly assigned to receive either a paper logbook (n =
171), a Web 1.0 (n = 165) or a Web 2.0 (n = 168) physical activity intervention.
Moderate to vigorous physical activity was measured using ActiGraph monitors at
baseline 3, 12 and 18 months. Website usage statistics including time on site,
number of log-ins and number of step entries were also recorded. Generalised
linear and intention-to-treat linear mixed models were used to test interactions
between intervention and age groups (<55y and >=55y) for website usage and
moderate to vigorous physical activity changes. RESULTS: Time on site was higher
for the Web 2.0 compared to the Web 1.0 intervention from baseline to 3 months,
and this difference was significantly greater in the older group (OR = 1.47,
95%CI = 1.01-2.14, p = .047). Participants in the Web 2.0 group increased their
activity more than the logbook group at 3 months, and this difference was
significantly greater in the older group (moderate to vigorous physical activity
adjusted mean difference = 13.74, 95%CI = 1.08-26.40 min per day, p = .03). No
intervention by age interactions were observed for Web 1.0 and logbook groups.
CONCLUSIONS: Results partially support the use of Web 2.0 features to improve
adults over 55 s' engagement in and behaviour changes from web-based physical
activity interventions. TRIAL REGISTRATION: ACTRN ACTRN12611000157976 ,
Registered 7 March 2011.
PMID- 29329588
TI - Accuracy of four mononucleotide-repeat markers for the identification of DNA
mismatch-repair deficiency in solid tumors.
AB - BACKGROUND: To screen tumors with microsatellite instability (MSI) arising due to
DNA mismatch repair deficiency (dMMR), a panel of five quasi-monomorphic
mononucleotide-repeat markers amplified in a multiplex PCR (Pentaplex) are
commonly used. In spite of its several strengths, the pentaplex assay is not
robust at detecting the loss of MSH6-deficiency (dMSH6). In order to overcome
this challenge, we designed this study to develop and optimize a panel of four
quasi-monomorphic mononucleotide-repeat markers (Tetraplex) for identifying solid
tumors with dMMR, especially dMSH6. METHODS: To improve the sensitivity for
tumors with dMMR, we established a quasi-monomorphic variant range (QMVR) of 3-4
bp for the four Tetraplex markers. Thereafter, to confirm the accuracy of this
assay, we examined 317 colorectal cancer (CRC) specimens, comprising of 105 dMMR
[45 MutL homolog (MLH)1-deficient, 45 MutS protein homolog (MSH)2-deficient, and
15 MSH6-deficient tumors] and 212 MMR-proficient (pMMR) tumors as a test set. In
addition, we analyzed a cohort of 138 endometrial cancers (EC) by
immunohistochemistry to determine MMR protein expression and validation of our
new MSI assay. RESULTS: Using the criteria of >= 1 unstable markers as MSI
positive tumor, our assay resulted in a sensitivity of 97.1% [95% confidence
interval (CI) = 91.9-99.0%] for dMMR, and a specificity of 95.3% (95% CI = 91.5
97.4%) for pMMR CRC specimens. Among the 138 EC specimens, 41 were dMMR according
to immunohistochemistry. Herein, our Tetraplex assay detected dMMR tumors with a
sensitivity of 92.7% (95% CI = 80.6-97.5%) and a specificity of 97.9% (95% CI =
92.8-99.4%) for pMMR tumors. With respect to tumors with dMSH6, in the CRC
validation set, Tetraplex detected dMSH6 tumors with a sensitivity of 86.7% (13
of 15 dMSH6 CRCs), which was subsequently validated in the EC test set as well
(sensitivity, 75.0%; 6 of 8 dMSH6 ECs). CONCLUSIONS: Our newly optimized
Tetraplex system will help offer a robust and highly sensitive assay for the
identification of dMMR in solid tumors.
PMID- 29329589
TI - Enhanced metastatic capacity of breast cancer cells after interaction and hybrid
formation with mesenchymal stroma/stem cells (MSC).
AB - BACKGROUND: Fusion of breast cancer cells with tumor-associated populations of
the microenvironment including mesenchymal stroma/stem-like cells (MSC)
represents a rare event in cell communication whereby the metastatic capacity of
those hybrid cells remains unclear. METHODS: Functional changes were investigated
in vitro and in vivo following spontaneous fusion and hybrid cell formation
between primary human MSC and human MDA-MB-231 breast cancer cells. Thus,
lentiviral eGFP-labeled MSC and breast cancer cells labeled with mcherry resulted
in dual-fluorescing hybrid cells after co-culture. RESULTS: Double FACS sorting
and single cell cloning revealed two different aneuploid male hybrid populations
(MDA-hyb1 and MDA-hyb2) with different STR profiles, pronounced telomerase
activities, and enhanced proliferative capacities as compared to the parental
cells. Microarray-based mRNA profiling demonstrated marked regulation of genes
involved in epithelial-mesenchymal transition and increased expression of
metastasis-associated genes including S100A4. In vivo studies following
subcutaneous injection of the breast cancer and the two hybrid populations
substantiated the in vitro findings by a significantly elevated tumor growth of
the hybrid cells. Moreover, both hybrid populations developed various distant
organ metastases in a much shorter period of time than the parental breast cancer
cells. CONCLUSION: Together, these data demonstrate spontaneous development of
new tumor cell populations exhibiting different parental properties after close
interaction and subsequent fusion of MSC with breast cancer cells. This formation
of tumor hybrids contributes to continuously increasing tumor heterogeneity and
elevated metastatic capacities.
PMID- 29329590
TI - Frequent overexpression of AMAP1, an Arf6 effector in cell invasion, is
characteristic of the MMTV-PyMT rather than the MMTV-Neu human breast cancer
model.
AB - BACKGROUND: The small GTPase Arf6 and its downstream effector AMAP1 (also called
ASAP1/DDEF1) constitute a signaling pathway promoting cell invasion, in which
AMAP1 interacts with several different proteins, including PRKD2, EPB41L5,
paxillin, and cortactin. Components of this pathway are often overexpressed in
human breast cancer cells, to be correlated with poor prognosis of the patients,
whereas overexpression of the Arf6 pathway did not correlate with the four main
molecular classes of human breast tumors. In this pathway, receptor tyrosine
kinases, including EGFR and Her2, activate Arf6 via GEP100. MMTV-PyMT mice and
MMTV-Neu mice are well-established models of human breast cancer, and exhibit the
early dissemination and the lung metastasis, by utilizing protein tyrosine
phosphorylation for oncogenesis. PyMT-tumors and Neu-tumors are known to have
overlapping gene expression profiles, which primarily correspond to the luminal B
type of human mammary tumors, although they differ in the time necessary for
tumor onset and metastasis. Given the common usage of protein tyrosine
phosphorylation, as well as the frequent use of these animal models for studying
breast cancer at the molecular level, we here investigated whether mammary tumors
in these mouse models utilize the Arf6-based pathway for invasion. METHODS:
Expression levels of Arf6, AMAP1, and GEP100 were analyzed in PyMT-tumors and Neu
tumors by western blotting. Expression of Arf6 and AMAP1 was also analyzed by
immunohistochemistry. The involvement of AMAP1 in invasion, and the possible
correlation of its high expression levels with cancer mesenchymal properties were
also investigated. RESULTS: We found that PyMT-tumors, but not Neu-tumors,
frequently overexpress AMAP1 and use it for invasion, whereas both types of
tumors expressed Arf6 and GEP100 at different levels. High levels of the AMAP1
expression among PyMT-tumor cells were frequently correlated with loss of the
epithelial marker CK8 and also with expression of the mesenchymal marker vimentin
both at the primary sites and at sites of the lung metastases. CONCLUSIONS: PyMT
tumors appear to frequently utilize the Arf6-based invasive machinery, whereas
Neu-tumors do not. Our results suggest that MMTV-PyMT mice, rather than MMTV-Neu
mice, are useful to study the Arf6-based mammary tumor malignancies, as a
representative model of human breast cancer.
PMID- 29329592
TI - The eXtensible ontology development (XOD) principles and tool implementation to
support ontology interoperability.
AB - Ontologies are critical to data/metadata and knowledge standardization, sharing,
and analysis. With hundreds of biological and biomedical ontologies developed, it
has become critical to ensure ontology interoperability and the usage of
interoperable ontologies for standardized data representation and integration.
The suite of web-based Ontoanimal tools (e.g., Ontofox, Ontorat, and Ontobee)
support different aspects of extensible ontology development. By summarizing the
common features of Ontoanimal and other similar tools, we identified and proposed
an "eXtensible Ontology Development" (XOD) strategy and its associated four
principles. These XOD principles reuse existing terms and semantic relations from
reliable ontologies, develop and apply well-established ontology design patterns
(ODPs), and involve community efforts to support new ontology development,
promoting standardized and interoperable data and knowledge representation and
integration. The adoption of the XOD strategy, together with robust XOD tool
development, will greatly support ontology interoperability and robust ontology
applications to support data to be Findable, Accessible, Interoperable and
Reusable (i.e., FAIR).
PMID- 29329591
TI - Prospects for chimeric antigen receptor-modified T cell therapy for solid tumors.
AB - The potential for adoptive cell immunotherapy as a treatment against cancers has
been demonstrated by the remarkable response in some patients with hematological
malignancies using autologous T cells endowed with chimeric antigen receptors
(CARs) specific for CD19. Clinical efficacy of CAR-T cell therapy for the
treatment of solid tumors, however, is rare due to physical and biochemical
factors. This review focuses on different aspects of multiple mechanisms of
immunosuppression in solid tumors. We characterize the current state of CAR
modified T cell therapy and summarize the various strategies to combat the
immunosuppressive microenvironment of solid tumors, with the aim of promoting T
cell cytotoxicity and enhancing tumor cell eradication.
PMID- 29329593
TI - Targeting ectodysplasin promotor by CRISPR/dCas9-effector effectively induces the
reprogramming of human bone marrow-derived mesenchymal stem cells into sweat
gland-like cells.
AB - BACKGROUND: Patients with a deep burn injury are characterized by losing the
function of perspiration and being unable to regenerate the sweat glands. Because
of their easy accession, multipotency, and lower immunogenicity, bone marrow
derived mesenchymal stem cells (BM-MSCs) represent as an ideal biological source
for cell therapy. The aim of this study was to identify whether targeting the
promotor of ectodysplasin (EDA) by CRISPR/dCas9-effector (dCas9-E) could induce
the BM-MSCs to differentiate into sweat gland-like cells (SGCs). METHODS:
Activation of EDA transcription in BM-MSCs was attained by transfection of naive
BM-MSCs with the lenti-CRISPR/dCas9-effector and single-guide RNAs (sgRNAs). The
impact of dCas9-E BM-MSCs on the formation of SGCs and repair of burn injury was
identified and evaluated both in vitro and in a mouse model. RESULTS: After
transfection with sgRNA-guided dCas9-E, the BM-MSCs acquired significantly higher
transcription and expression of EDA by doxycycline (Dox) induction. Intriguingly,
the specific markers (CEA, CK7, CK14, and CK19) of sweat glands were also
positive in the transfected BM-MSCs, suggesting that EDA plays a critical role in
promoting BM-MSC differentiation into sweat glands. Furthermore, when the dCas9-E
BM-MSCs with Dox induction were implanted into a wound in a laboratory animal
model, iodine-starch perspiration tests revealed that the treated paws were
positive for perspiration, while the paws treated with saline showed a negative
manifestation. For the regulatory mechanism, the expression of downstream genes
of NF-kappaB (Shh and cyclin D1) was also enhanced accordingly. CONCLUSIONS:
These results suggest that EDA is a pivotal factor for sweat gland regeneration
from BM-MSCs and may also offer a new approach for destroyed sweat glands and
extensive deep burns.
PMID- 29329594
TI - Modelling the structure of a ceRNA-theoretical, bipartite microRNA-mRNA
interaction network regulating intestinal epithelial cellular pathways using R
programming.
AB - OBJECTIVE: We report a method using functional-molecular databases and network
modelling to identify hypothetical mRNA-miRNA interaction networks regulating
intestinal epithelial barrier function. The model forms a data-analysis component
of our cell culture experiments, which produce RNA expression data from
Nanostring Technologies nCounter(r) system. The epithelial tight-junction (TJ)
and actin cytoskeleton interact as molecular components of the intestinal
epithelial barrier. Upstream regulation of TJ-cytoskeleton interaction is
effected by the Rac/Rock/Rho signaling pathway and other associated pathways
which may be activated or suppressed by extracellular signaling from growth
factors, hormones, and immune receptors. Pathway activations affect epithelial
homeostasis, contributing to degradation of the epithelial barrier associated
with osmotic dysregulation, inflammation, and tumor development. The complexity
underlying miRNA-mRNA interaction networks represents a roadblock for prediction
and validation of competing-endogenous RNA network function. RESULTS: We
developed a network model to identify hypothetical co-regulatory motifs in a
miRNA-mRNA interaction network related to epithelial function. A mRNA-miRNA
interaction list was generated using KEGG and miRWalk2.0 databases. R-code was
developed to quantify and visualize inherent network structures. We identified a
sub-network with a high number of shared, targeting miRNAs, of genes associated
with cellular proliferation and cancer, including c-MYC and Cyclin D.
PMID- 29329595
TI - Human umbilical cord mesenchymal stem cell conditioned medium attenuates renal
fibrosis by reducing inflammation and epithelial-to-mesenchymal transition via
the TLR4/NF-kappaB signaling pathway in vivo and in vitro.
AB - BACKGROUND: Renal fibrosis is characterized by infiltration of interstitial
inflammatory cells and release of inflammatory mediators, activation and
proliferation of fibroblasts, and deposition of excessive extracellular matrix
(ECM). The aim of this study was to evaluate the effect of human umbilical cord
derived mesenchymal stem cell (hucMSC) conditioned medium (CM) on renal
tubulointerstitial inflammation and fibrosis. METHODS: Renal interstitial
fibrosis was prepared in vivo using the unilateral ureteral obstruction (UUO).
Rats were divided randomly into Sham group, Sham group with CM, UUO group, and
UUO group with CM. The effect of hucMSC-CM on kidney injury induced by UUO was
assessed by detecting kidney histopathology, serum creatinine (SCr), and blood
urea nitrogen (BUN). The levels of TNF-alpha, IL-6, and IL-1beta in serum and
kidney tissues were detected by ELISA. The expression of proteins associated with
fibrosis and renal inflammation was investigated using immunohistochemical
staining and western blotting. The effects of hucMSC-CM on the TGF-beta1-induced
epithelial-mesenchymal transition (EMT) process and on inflammation in NRK-52E
cells were investigated by immunofluorescent staining, ELISA, and western
blotting. RESULTS: hucMSC-CM reduced extracellular matrix deposition and
inflammatory cell infiltration as well as release of inflammatory factors in UUO
induced renal fibrosis. Furthermore, hucMSC-CM markedly attenuated the EMT
process and proinflammatory cytokines in rats with UUO and TGF-beta1-induced NRK
52E cells. hucMSC-CM also inhibited the TLR4/NF-kappaB signaling pathway in vivo
and in vitro. CONCLUSIONS: Our results suggest that hucMSC-CM has protective
effects against UUO-induced renal fibrosis and that hucMSC-CM exhibits its anti
inflammatory effects through inhibiting TLR4/NF-kappaB signaling pathway
activation.
PMID- 29329596
TI - The epidemiology of psoriatic arthritis in Israel - a population-based study.
AB - BACKGROUND: There is limited information on the epidemiology of psoriatic
arthritis (PsA) in general and in Middle Eastern populations in particular. The
aims of this study were to estimate the prevalence and incidence rates of PsA and
their temporal trends in the general population in Israel. METHODS: In this
study, a cohort of adult patients with PsA was derived from the database of
Clalit Health Services (CHS), Israel's largest health fund, with over 4.4 million
members. The crude and age- and sex-standardized prevalence and incidence rates
of PsA from 2006 to 2015 in the general population were calculated. The variation
in PsA prevalence was assessed in relation to several demographic factors.
RESULTS: Among the 2,931,199 individuals aged 18 years and older registered in
the CHS database in 2015, 4490 patients had a diagnosis of PsA (322 incident
cases), resulting in overall crude prevalence and incidence rates of 0.153% (95%
CI 0.149%, 0.158%) and 10.9 (95% CI 9.8, 12.3) per 100,000 population,
respectively. The reported prevalence of PsA in Israel has doubled between 2006
and 2015 (from 0.073% to 0.153%). In contrast, the global incidence rate remained
stable, with a gradual increase in incidence among individuals aged 51 to 70
years. PsA is associated with Jewish ethnicity, high socioeconomic status, and
higher body mass index. CONCLUSIONS: The prevalence and incidence of PsA in
Israel are within the range of previous estimates from Southern European
populations. An increase in the reported prevalence of PsA was observed over the
past decade in the general population in Israel.
PMID- 29329597
TI - Does cognitive behavioral therapy alter mental defeat and cognitive flexibility
in patients with panic disorder?
AB - OBJECTIVE: Mental defeat and cognitive flexibility have been studied as
explanatory factors for depression and posttraumatic stress disorder. This study
examined mental defeat and cognitive flexibility scores in patients with panic
disorder (PD) before and after cognitive behavioral therapy (CBT), and compared
them to those of a gender- and age-matched healthy control group. RESULTS:
Patients with PD (n = 15) received 16 weekly individual CBT sessions, and the
control group (n = 35) received no treatment. Patients completed the Mental
Defeat Scale and the Cognitive Flexibility Scale before the intervention,
following eight CBT sessions, and following 16 CBT sessions, while the control
group did so only prior to receiving CBT (baseline). The patients' pre-CBT Mental
Defeat and Cognitive Flexibility Scale scores were significantly higher on the
Mental Defeat Scale and lower on the Cognitive Flexibility Scale than those of
the control group participants were. In addition, the average Mental Defeat Scale
scores of the patients decreased significantly, from 22.2 to 12.4, while their
average Cognitive Flexibility Scale scores increased significantly, from 42.8 to
49.5. These results suggest that CBT can reduce mental defeat and increase
cognitive flexibility in patients with PD Trial registration The study was
registered retrospectively in the national UMIN Clinical Trials Registry on June
10, 2016 (registration ID: UMIN000022693).
PMID- 29329598
TI - Treatment outcome of anti-angiogenesis through VEGF-pathway in the management of
gastric cancer: a systematic review of phase II and III clinical trials.
AB - OBJECTIVES: Advanced gastric cancer poses a therapeutic challenge worldwide. In
randomised clinical trials, anti-VEGF has been reported as an essential agent for
the treatment of advanced gastric cancer. This review aims at assessing the
treatment outcome of anti-angiogenesis therapy through the VEGF pathway in the
management of patients with advanced gastric cancer. RESULTS: During this review,
38 clinical trials were identified. Of these, 30 clinical trials were excluded,
leaving eight trials of phase II and III. Ramucirumab, as a second line treatment
of advanced gastric cancer, decreases the risk of disease progression (37-52%)
and death (19-22%). Compare ramucirumab and bevacizumab in combination with
traditional chemotherapy; ramucirumab has shown to improve progression-free
survival and overall survival. Apatinib tyrosine kinase inhibitor combined with
traditional chemotherapy has shown to improve overall response rate and
progression-free survival with marginal improvements in overall survival.
Chemotherapy, in combination with anti-VEGF drugs, in the management of advanced
gastric cancer significantly improves the outcome of overall response rate,
progression-free survival and overall survival when compared to chemotherapy
alone. Therefore, we recommend that anti-VEGF drugs are the drugs of choice in
the management of patients with advanced gastric cancer.
PMID- 29329599
TI - Gallbladder ascariasis in Kosovo - focus on ultrasound and conservative therapy:
a case series.
AB - BACKGROUND: Ascaris lumbricoides is one of the most common intestinal infections
in developing countries, including Kosovo. In contrast to migration to the bile
duct, migration of the worm to the gallbladder, due to the narrow and tortuous
nature of the cystic duct, is rare. When it does occur, it incites acalculous
cholecystitis. CASE PRESENTATIONS: This case series describes a 16-month-old
Albanian girl, a 22-month-old Albanian girl, a 4-year-old Albanian girl, and a 10
year-old Albanian boy. Here we report our experience with gallbladder ascariasis
including clinical manifestations, diagnostic procedures, and treatment. Fever,
diarrhea and vomiting, dehydration, pale appearance, and weakness were the
manifestations of the primary disease. In all patients, a physical examination
revealed reduced turgor and elasticity of the skin. Abdomen was at the level of
the chest, soft, with minimal palpatory pain. The liver and spleen were not
palpable. A laboratory examination was not specific except for eosinophilia.
There were no pathogenic bacteria in coproculture but Ascaris was found in all
patients. At an ultrasound examination in all cases we found single, long, linear
echogenic structure without acoustic shadowing containing a central, longitudinal
anechoic tube with characteristic movement within the gallbladder. Edema of the
gallbladder wall was suggestive of associated inflammation. There were no other
findings on adjacent structures and organs. All patients received mebendazole 100
mg twice a day for 3 days. They also received symptomatic therapy for
gastroenteritis. Because of elevated markers of inflammation all patients were
treated with antibiotics, assuming acute cholecystitis, although ultrasound was
able to confirm cholecystitis in only two of our four patients. Since the length
of stay was dependent on the primary pathology it was 7 to 10 days. At control
ultrasounds on 14th day, third and sixth month, all patients were free of
ascariasis. CONCLUSIONS: Gallbladder ascariasis should be considered in all
patients presenting with abdominal pain, distension, colic, nausea, anorexia, and
intermittent diarrhea associated with jaundice, nausea, vomiting, fever, and
severe radiating pain. Eosinophilia, ova, and parasites on stool examination as
well as an anechogenic tube with characteristic movement within the bile duct
found on abdominal ultrasound are conclusive for diagnosis. Mebendazole is an
effective drug for the treatment. Surgical treatment is rarely needed.
PMID- 29329600
TI - Optimal waist circumference cut-off points for predicting metabolic syndrome
among low-income black South African adults.
AB - OBJECTIVE: Waist circumference has been identified as one of the strongest
predictive tool for metabolic syndrome. This study determines the optimal cut-off
point of waist circumference for metabolic syndrome among low-income earning
South African black population, in Eastern Cape, South Africa. The optimal waist
circumference cut-off point was determined through receiver operating
characteristics analysis using the maximum Youden index. RESULTS: Among men,
waist circumference at a cut-off value of 95.25 cm yielded the highest Youden
index of 0.773 (sensitivity = 98%, specificity = 79%, area under curve 0.893).
For women, waist circumference of 89.45 cm yielded the highest Youden index of
0.339 (sensitivity = 88%, specificity = 46%, area under curve 0.713). The
prevalence of metabolic syndrome among men, women and both sexes using the new
cut-off points were: 17.8, 20.8 and 17.7%, respectively, compared to; 15.6, 24.8
and 21.8%, using the traditional cut-off values of 94 and 80 cm for men and
women, respectively. The traditional waist circumference value slightly under
estimated the prevalence of metabolic syndrome among men and over-estimated among
women and the overall population. A specific waist circumference cut-off point
for South African blacks is needed for correct identification of the metabolic
state of the populace in order to develop appropriate interventions.
PMID- 29329601
TI - Nicotiana glauca whole-genome investigation for cT-DNA study.
AB - OBJECTIVE: Nicotiana glauca (tree tobacco) is a naturally transgenic plant,
containing sequences acquired from Agrobacterium rhizogenes by horizontal gene
transfer. Besides, N. glauca contains a wide profile of alkaloids of medical
interest. DATA DESCRIPTION: We report a high-depth sequencing and de novo
assembly of N. glauca full genome and analysis of genome elements with bacterial
origin. The draft genome assembly is 3.2 Gb, with N50 size of 31.1 kbp.
Comparative analysis confirmed the presence of single, previously described gT
insertion. No evidence was acquired to support idea of multiple T-DNA insertions
in the N. glauca genome. Our data is the first comprehensive de novo assembly of
tree tobacco and provide valuable information for researches in pharmacological
and in phylogenetic fields.
PMID- 29329602
TI - Abatacept used in combination with non-methotrexate disease-modifying
antirheumatic drugs: a descriptive analysis of data from interventional trials
and the real-world setting.
AB - BACKGROUND: Methotrexate (MTX) remains the anchor drug in rheumatoid arthritis
(RA) treatment, but is poorly tolerated or contraindicated in some patients.
There is a wealth of data supporting the use of abatacept in combination with
MTX, but data on alternative conventional synthetic disease-modifying
antirheumatic drug (csDMARD) combinations with abatacept are scarce. METHODS: In
this post-hoc exploratory analysis, efficacy and safety data were extracted from
abatacept RA studies in which combination with csDMARDs other than MTX was
permitted: three interventional trials (ATTAIN, ASSURE, and ARRIVE) and one real
world study (ACTION). Patients with moderate-to-severe RA received abatacept in
combination with MTX, hydroxychloroquine, sulfasalazine, azathioprine, or
leflunomide for 6 months to 2 years according to the study design. Change from
baseline in physical function (Health Assessment Questionnaire-Disability Index
(HAQ-DI); all studies) and 28-joint Disease Activity Score (C-reactive protein)
(DAS28 (CRP); ATTAIN, ARRIVE, and ACTION), American College of Rheumatology
response rates (ATTAIN), and safety were assessed for individual and pooled
csDMARD combinations for each trial. A meta-analysis was also performed on pooled
data for HAQ-DI and DAS28 (CRP) across interventional trials. RESULTS: Across all
four studies, 731 patients received abatacept plus one non-MTX csDMARD
(hydroxychloroquine n = 152; sulfasalazine n = 123; azathioprine n = 59; and
leflunomide n = 397) and 2382 patients received abatacept plus MTX. Mean changes
from baseline in HAQ-DI scores for abatacept plus MTX (all csDMARDs pooled) vs
abatacept plus a non-MTX csDMARD were -0.54 vs -0.44 (ATTAIN), -0.43 vs -0.43
(ASSURE), and -0.39 vs -0.36 (ARRIVE). Mean changes from baseline in DAS28 (CRP)
and ACR response rates were also similar with abatacept plus MTX or non-MTX
csDMARDs. Data for individual non-MTX csDMARDs (pooled across studies) and real
world data were consistent with these findings. Rates of treatment-related
adverse events and serious adverse events, respectively, for abatacept plus one
non-MTX csDMARD vs abatacept plus MTX were 35.7% vs 41.7% and 2.4% vs 2.3%
(ATTAIN), 58.0% vs 55.9% and 4.2% vs 1.7% (ASSURE), and 38.1% vs 44.3% and 0.6%
vs 2.9% (ARRIVE). CONCLUSIONS: Abatacept in combination with non-MTX csDMARDs is
clinically effective and well tolerated in patients with moderate-to-severe RA,
providing similar benefits to those seen with abatacept plus MTX. TRIAL
REGISTRATION: ClinicalTrials.gov NCT00048581 . Registered 2 November 2002.
ClinicalTrials.gov NCT00048932 . Registered 11 November 2002. ClinicalTrials.gov
NCT00124982 . Registered 30 June 2005. ClinicalTrials.gov NCT02109666 .
Registered 8 April 2014.
PMID- 29329603
TI - Green Tobacco Sickness among Brazilian farm workers and genetic polymorphisms.
AB - OBJECTIVE: Green Tobacco Sickness (GTS) is an occupational illness caused by
dermal absorption of nicotine from tobacco leaves. It affects thousands of farm
workers worldwide. Brazil is the second tobacco producer in the world; despite
this, there are few studies on GTS among Brazilian harvesters. This study aimed
to determine the prevalence of GTS among a population of tobacco workers from a
producing area in northeastern Brazil and investigate whether the occurrence of
the disease was influenced by factors such age, gender and smoking status. In
addition, it was investigated if there was association between the onset of GTS
and genetic polymorphisms in genes that encode some detoxification enzymes. A
semi-structured questionnaire was used to collect demographic, behavioral and
occupational data from the referred workers. Polymorphisms were tested through
the Polymerase Chain Reaction technique. RESULTS: The total prevalence of GTS
found was 56.9%, with a significant difference between genders (71.7% for women
and 35.3% for men, p < 0.0001). No association was identified between the
investigated polymorphisms and GTS. This study confirms the occurrence of GTS
among tobacco harvesters in Brazil with high prevalence. The investigation
suggests the need to take preventive measures to protect tobacco workers against
this disease.
PMID- 29329607
TI - The genus Liriope: Phytochemistry and pharmacology.
AB - Liriope (Liliaceae) species have been used as folk medicines in Asian countries
since ancient times. From Liriope plants (8 species), a total of 132 compounds
(except polysaccharides) have been isolated and identified, including steroidal
saponins, flavonoids, phenols, and eudesmane sesquiterpenoids. The crude extracts
or monomeric compounds from this genus have been shown to exhibit anti-tumor,
anti-diabetic, anti-inflammatory, and neuroprotective activities. The present
review summarizes the results on phytochemical and biological studies on Liriope
plants. The chemotaxonomy of this genus is also discussed.
PMID- 29329608
TI - Polyphenols isolated from Acacia mearnsii bark with anti-inflammatory and
carbolytic enzyme inhibitory activities.
AB - The present study was designed to characterize the polyphenols isolated from
Acacia mearnsii bark crude extract (B) and fractions (B1-B7) obtained by high
speed counter-current chromatography (HSCCC) and evaluate their anti-inflammatory
and carbolytic enzymes (alpha-glucosidase and alpha-amylase) inhibitory
activities. Fractions B4, B5, B6, B7 (total phenolics 850.3, 983.0, 843.9, and
572.5 mg.g-1, respectively; proanthocyanidins 75.7, 90.5, 95.0, and 44.8 mg.g-1,
respectively) showed significant activities against reactive oxygen species
(ROS), nitric oxide (NO) production, and expression of pro-inflammatory genes
interleukin-1beta (IL-1beta) and inducible nitric oxide synthase (iNOS) in a
lipopolysaccharide (LPS)-stimulated mouse macrophage cell line RAW 264.7. All the
extracts suppressed alpha-glucosidase and alpha-amylase activities, two primary
enzymes responsible for carbohydrate digestion. A. mearnsii bark samples
possessed significantly stronger inhibitory effects against alpha-glucosidase
enzyme (IC50 of 0.4-1.4 MUg.mL-1) than the pharmaceutical acarbose (IC50 141.8
MUg.mL-1). B6 and B7 (IC50 17.6 and 11.7 MUg.mL-1, respectively) exhibited alpha
amylase inhibitory activity as efficacious as acarbose (IC50 15.4 MUg.mL-1).
Moreover, B extract, at 25 ug.mL-1, significantly decreased the non-mitochondrial
oxidative burst that is often associated with inflammatory response in human
monocytic macrophages.
PMID- 29329609
TI - Garcinia xanthochymus extract protects PC12 cells from H2O2-induced apoptosis
through modulation of PI3K/AKT and NRF2/HO-1 pathways.
AB - The aim of the present study was to investigate the protective effects and
underlying mechanisms of Garcinia xanthochymus, a perennial medicinal plant
native to Yunnan, China, against H2O2-induced oxidative damage in rat
pheochromacytoma PC12 cells. Preincubation of PC12 cells with fruit EtOAc
fraction (fruit-EFr., 12.5-50 umol.L-1) of G. xanthochymus for 24 h prior to H2O2
exposure markedly improved cell viability and increased the activities of
antioxidant enzymes (superoxide dismutase, catalase, and heme oxygenase-1 [HO
1]), prevented lactate dehydrogenase release and lipid peroxidation
malondialdehyde production, attenuated the decrease of matrix metalloproteinases
(MMP), and scavenged reactive oxygen species (ROS). Fruit-EFr. also reduced BAX
and cytochrome C expression and improved BCL-2 expression, thereby decreasing the
ratio of BAX to BCL-2. Fruit-EFr. activated the nuclear translocation of NRF2 to
increase HO-1 and induced the phosphorylation of AKT. Its cytoprotective effect
was abolished by LY294002, a specific inhibitor of PI3K. Taken together, the
above findings suggested that fruit-EFr.of G. xanthochymus could enhance cellular
antioxidant defense capacity, at least in part, through upregulating HO-1
expression and activating the PI3K/AKT pathway and that it could suppress H2O2
induced oxidative damage via PI3K/AKT and NRF2/HO-1 signaling pathways.
PMID- 29329610
TI - Bacopa monnieri extracts prevent hydrogen peroxide-induced oxidative damage in a
cellular model of neuroblastoma IMR32 cells.
AB - Neurodegenerative diseases are the consequences of imbalance between the
production of oxidative stress and its nullification by cellular defense
mechanisms. Hydrogen peroxide (H2O2), a precursor of deleterious reactive oxygen
species, elicits oxidative stress, resulting in severe brain injuries. Bacopa
monnieri is well known for its nerve relaxing and memory enhancing properties.
The present study was designed to evaluate the protective effects of extracts
from Bacopa monnieri against H2O2 induced oxidative stress using a cellular
model, neuroblastoma IMR32 cell line. The protective potential of methanolic,
ethanolic, and water extracts of B. monnieri (BM-MEx, BM-EEx, and BM-WEx) was
evaluated using MTT assay. Although, all the B. monnieri extracts were found to
protect cells against H2O2-mediated stress but BM-MEx showed significantly
greater protection. UPLC analysis of BM-MEx revealed various polyphenols,
including quercetin, catechin, umbelliferone, and caffeic acid predominance.
Further, BM-MEx was found to possess considerable greater neuroprotective
potential in comparison to the standard polyphenols such as quercetin, catechin,
umbelliferone, and caffeic acid. The levels of antioxidant enzymes were
significantly elevated after the pretreatment of BM-MEx and quercetin. The
expression levels of oxidative stress markers, such as NF200, HSP70, and
mortalin, were significantly alleviated after the pretreatment of BM-MEx as shown
by immunofluorescence and RT-PCR. In conclusion, the present study demonstrated
the protective effects of BM-MEx, suggesting that it could be a candidate for the
development of neuropathological therapeutics.
PMID- 29329611
TI - Early intervention with Didang decoction delays macrovascular lesions in diabetic
rats through regulating AMP-activated protein kinase signaling pathway.
AB - The study aimed to investigate the intervening role of Didang decoction (DDD) at
different times in macrovascular endothelial defense function, focusing on its
effects on the AMP-activated protein kinase (AMPK) signaling pathway. The effects
of DDD on mitochondrial energy metabolism were also investigated in rat aortic
endothelial cells (RAECs). Type 2 diabetes were induced in rats by streptozotocin
(STZ) combined with high fat diet. Rats were randomly divided into non
intervention group, metformin group, simvastatin group, and early-, middle-, late
stage DDD groups. Normal rats were used as control. All the rats received 12
weeks of intervention or control treatment. Western blots were used to detect the
expression of AMP-activated protein kinase alpha1 (AMPKalpha1) and peroxisome
proliferator-activated receptor 1alpha (PGC-1alpha). Changes in the intracellular
AMP and ATP levels were detected with ELISA. Real-time-PCR was used to detect the
mRNA level of caspase-3, endothelial nitric oxide synthase (eNOS), and Bcl-2.
Compared to the diabetic non-intervention group, a significant increase in the
expression of AMPKalpha1 and PGC-1alpha were observed in the early-stage, middle
stage DDD groups and simvastatin group (P < 0.05). The levels of Bcl-2, eNOS, and
ATP were significantly increased (P < 0.05), while the level of AMP and caspase-3
were decreased (P < 0.05) in the early-stage DDD group and simvastatin group.
Early intervention with DDD enhances mitochondrial energy metabolism by
regulating the AMPK signaling pathway and therefore may play a role in
strengthening the defense function of large vascular endothelial cells and
postpone the development of macrovascular diseases in diabetes.
PMID- 29329612
TI - Clavuridins A and B, two new trinor-guaiane sesquiterpenes isolated from the
Xisha soft coral Clavularia viridis.
AB - In the present study, two new trinor-guaiane sesquiterpenes, named clavuridins B
(1), and A (2), along with three known sesquiterpenes (3-5), were isolated from
the Xisha soft coral Clavularia viridis. Their structures and absolute
configurations were determined on the basis of spectroscopic analysis, X-ray
diffraction analysis with Cu Kalpha radiation and by comparison with related
model compounds. Compounds 1 and 3-5 were evaluated for their cytotoxic activity.
PMID- 29329613
TI - New diterpenoids isolated from Leonurus japonicus and their acetylcholinesterase
inhibitory activity.
AB - Three new labdane diterpenoids, leojaponicone A (1), isoleojaponicone A (2) and
methylisoleojaponicone A (3), were isolated from the herb of Leonurus japonicus.
The chemical structures of these secondary metabolites were elucidated on the
basis of 1D and 2D NMR, including HMQC, and HMBC spectroscopic techniques. All
the new compounds were tested in vitro for their acetylcholinesterase and alpha
glucosidase inhibitory activity. Compounds 1-3 exhibited low inhibitory effects
on alpha-glucosidase with respect to acarbose and exhibited high inhibitory
effects on acetylcholinesterase with respect to huperzine A.
PMID- 29329614
TI - Bioassay-guided isolation of novel and selective urease inhibitors from Diospyros
lotus.
AB - Two new dimeric naphthoquinones, 5',8'-dihydroxy-6,6'-dimethyl-7,3'-binaphthyl
1,4,1',4'-tetraone (1; Di-naphthodiospyrol D) and 5',8'-dihydroxy-5,8-dimethoxy
6,6'-dimethyl-7,3'-binaphthyl-1,4,1',4'-tetraone (2; Di-naphthodiospyrol E),
along with known naphthoquinones diospyrin (3) and 8-hydroxy diospyrin (4) were
isolated from the chloroform fraction of extract of Diospyros lotus roots. Their
structures were elucidated by advanced spectroscopic analyses, including HSQC,
HMBC, NOESY, and J-resolved NMR experiments. The fractions and compounds 1-4 were
evaluated for urease activity and phosphodiesterase-I, carbonic anhydrase-II and
alpha-chymotrypsin enzyme inhibitory activities. Compounds 1 and 2 and their
corresponding fractions showed significant and selective inhibitory effects on
urease activities. The IC50 values of 1 and 2 were 260.4 +/- 6.37 and 381.4 +/-
4.80 umol.L-1, respectively, using thiourea (IC50 = 21 +/- 0.11 umol.L-1) as the
standard inhibitor. This was the first report demonstrating that the
naphthoquinones class showed urease inhibition.
PMID- 29329615
TI - Synthesis and cytotoxicity evaluation of 3-amino-2-hydroxypropoxygenistein
derivatives.
AB - Soy isoflavones exhibit various biological activities, such as antioxidant, anti
tumor, anti-inflammatory, and cardiovascular protective effects. The present
study was designed to investigate the effects of sixteen synthesized 3-amino-2
hydroxypropoxy genistein derivatives on cell proliferation and activation of Nrf2
(Nuclear factor erythroid 2-related factor 2)/ARE (antioxidant response elements)
pathway in human cancer cell lines. Most of the tested compounds exerted greater
cytotoxic activity than genistein, as measured by MTT assay. Moreover, compound
8c showed the highest ARE-luciferase reporter activity among the test compounds.
It strongly promoted Nrf2 nuclear translocation and up-regulated the expression
of total Nrf2 and downstream targets NQO-1 and HO-1 at protein level. The present
study may provide a basis for the application of isoflavone derivatives as
Nrf2/ARE pathway inducers for cancer therapy and cancer prevention.
PMID- 29329616
TI - Scientific integrity includes the rigour of the methods.
PMID- 29329617
TI - DNA detection of Trypanosoma evansi: Diagnostic validity of a new assay based on
loop-mediated isothermal amplification (LAMP).
AB - Trypanosoma evansi (T. evansi) is the most widely spread pathogenic trypanosome
in the world. The control of trypanosomiasis depends on accurate diagnosis and
effective treatment. Focusing on the presence of T. evansi in Asia, we developed
a detection assay based on tracing phosphate ions (Pi) generated during LAMP
targeting the variant surface glycoprotein (VSG) gene of Rode Trypanozoon
antigenic type 1.2 (RoTat 1.2 VSG). The diagnostic potential as well as the use
of the assay as a test-of-cure method after berenil treatment, was assessed in
mice at different time points of infection. In addition, 67 buffalo blood
collected from Tongling county, Anhui province, as well as 42 cattle sera from
the Shanghai area, were used to evaluate the diagnostic validity of the test. The
detection limit of the novel LAMP assay was determined to be as low as 1 fg of T.
evansi DNA, while the reaction time for the test was only 30min. Hence it
outperforms both microscopy and PCR. In the test-of-cure assessment, successful
berenil mediated cure could be confirmed within 48h after treatment. This offers
a tremendous advantage over conventional antibody-based diagnostic tools in which
successful cure only can be confirmed after months. In the cattle and buffalo
screening, the LAMP was able to detect a false-negative determined sample,
wrongly classified in a conventional microscopy and PCR screening. Finally, no
cross-reactivity was observed with other zoonotic parasites, such as T. evansi
type B, T. congolense, T. brucei, Schistosoma japonicum, Plasmodium falciparum,
Leishmania donovani, Toxoplasma gondii and Angiostrongylus cantonensis. We
conclude that the novel LAMP assay is sensitive, specific and convenient for
field use, particularly in areas where infection incidence has become extremely
low. The LAMP assay could be used as a tool for trypanosomiasis control and
elimination strategies in areas where T. evansi Type A infections are causing a
threat to livestock farming.
PMID- 29329618
TI - Vaccination against Fasciola hepatica using cathepsin L3 and B3 proteases
delivered alone or in combination.
AB - No licensed vaccine is currently available for prevention of Fasciola hepatica
infections. However, considering the alarming increase in drug resistance, there
is an urgent need for a safe and fully effective vaccine against fasciolosis.
Here, we tested if cathepsins L (FhCL3-1, FhCL3-2) and B (FhCB3) secreted by
juvenile liver flukes are viable vaccine targets when delivered alone or in
combination in a rat model. Since control over the early immune response is
crucial for parasite's establishment in its host, it was hypothesised that
targeting fluke juvenile stages may prove beneficial. Moreover, it was assumed
that selected antigens will act in a cumulative manner to interfere with liver
fluke migration and thereby will reduce F. hepatica infection. Recombinant FhCL3
1 and FhCL3-2 delivered alone reduced liver fluke burdens by 47 % and 63 %,
respectively. A trivalent vaccine containing rFhCL3-1/CL3-2/CB3 did not increase
the protective vaccine efficacy compared to the rFhCL3-2 vaccinated group (53 %),
although, reductions in liver fluke wet weight (statistically significant) and
liver damage score were most pronounced. Further, the highest IgG1 and IgG2a
levels were seen in rFhCL3-2 vaccinated rats, the group for which the highest
reduction in worm burden was demonstrated. Moreover, IgG1 and IgG2a levels in
vaccinated rats were significantly elevated compared to those reported for
control groups up to 4 week post-infection. While the mechanism of protection
remains unknown, it appears that it depends on vaccine-induced antibodies
directed against cathepsins. The obtained results imply that F. hepatica juvenile
specific cathepsins are promising vaccine candidates that induce responses that
successfully target early migratory liver fluke stages. Now, the challenge is to
evaluate these juvenile-specific cathepsins for use in livestock.
PMID- 29329619
TI - Hepatic fibropoiesis in dogs naturally infected with Leishmania (Leishmania)
infantum treated with liposome-encapsulated meglumine antimoniate and
allopurinol.
AB - Hepatic fibropoiesis in canine visceral leishmaniasis (CVL) were evaluated by
histological (morphometrical collagen deposition) and immunohistochemical assays
characterizing alpha-actin (alpha-SMA), vimentin, calprotectin (L1 antigen), and
TGF-beta in 46 naturally infected dogs with Leishmania infantum treated with
liposome-encapsulated meglumine antimoniate and allopurinol separately and in
combination. Six treatment groups were defined: meglumine antimoniate
encapsulated in nanometric liposomes (LMA), allopurinol (ALLOP); liposome
encapsulated meglumine antomoniate combined with allopurinol (LMA+ALLOP); empty
liposomes (LEMP); empty liposomes combined with allopurinol (LEMP+ALLOP) and
saline. Relative liver weight was lower in LMA, LMA+ALLOP, and ALLOP groups
compared to the LEMP control. Significantly lower granulomatous chronic
inflammatory reaction was seen in the ALLOP group compared to a control group.
Calprotectin was lowest in liver of those dogs showing lower numbers of
intralobular hepatic granulomas. Collagen deposits were significantly higher in
LMA compared to ALLOP, LEMP+ALLOP, and Saline groups. LMA+ALLOP group collagen
deposition was higher than dogs treated only with allopurinol.
Immunohistochemical analysis showed significant higher alpha-SMA in hepatic
stellate cells (HSCs), hepatic perisinusoidal cells, in control groups than
LMA+ALLOP and LEMP+ALLOP. Alpha-actin and Vimentin positive cells were diffusely
distributed throughout the liver parenchyma in the hepatic lobule, mainly in
HSCs. Vimentin expression was significantly higher in the saline group than in
the ALLOP group. Our data suggest that allopurinol inhibits HSC and results in
lower collagen deposits in liver during CVL progression, as supported by the
significantly lower expression of TGF-beta in the ALLOP group compared to other
groups. Results demonstrated that treatment with allopurinol inhibited chronic
granulomatous inflammatory reaction and hepatic fibrosis in CVL.
PMID- 29329621
TI - First parasitological, histopathological and molecular characterization of
Echinococcus vogeli Rausch and Bernstein, 1972 from Cuniculus paca Linnaeus, 1766
in the Cerrado biome (Mato Grosso do Sul, Brazil).
AB - Polycystic echinococcosis (PE) is caused by Echinococcus vogeli metacestodes
(larval stage) in Neotropical countries. E. vogeli is trophically-transmitted
between predators bush dogs (Speothos venaticus) and prey pacas (Cuniculus paca).
In Brazil, reported PE cases are restricted to the Amazon biome. In this study,
metacestodes from a paca hunted in Mato Grosso do Sul state (Cerrado biome) were
identified morphological and histopathological techniques and further confirmed
by molecular testing (sequencing of cytochrome C oxidase subunit I (cox1) gene)
for the first time. Images of the whole liver showed superficial bubble-like
hepatic masses. The parasitological analysis revealed large hooks (41.3 +/- 1.2
MUm length/12.8 +/- 0.8 MUm width) and small hooks (33.0 +/- 1.5 MUm length/11.1
+/- 1.2 MUm width), consistent with E. vogeli. Microscopically, the liver showed
protoscoleces, a thick laminated layer, fibrosis, and inflammatory infiltrate in
the adventitial layer. The DNA sequencing confirmed E. vogeli with 99% homology
with sequences deposited in the GenBank. In addition, this finding greatly
extends the geographic range of animal polycystic echinococcosis into the
Cerrado. It is likely to occur in new biomes, where bush dogs and pacas share a
given area in a trophic relationship.
PMID- 29329620
TI - Determination and validation of discriminating concentration of ivermectin
against Rhipicephalus microplus.
AB - Rhipicephalus microplus, the major cattle tick species of India is prevalent all
over the country and causes huge economic loss directly or indirectly to the
dairy industries. Chemical acaricides are playing an important role in managing
tick infestations on livestock for many years and consequently, resistance to
commonly used organophosphate (OP) and synthetic pyrethroid (SP) compounds has
been reported. Subsequently, ivermectin (IVM) has been emerged as an alternative
to manage OP and SP resistant ticks. However, with the increase of use during the
last 5-8 years, there is a possibility of development of resistance and thus
there is an urgent need to develop a robust resistance monitoring tool to
safeguard the drug. Lethal concentrations for 50 and 95% mortality of treated
ticks were determined to work out discriminating concentration (DC) in order to
diagnose resistance in the field situation. The DC (2 x LC95) was determined as
93.54 ppm using an established reference susceptible IVRI-1 line of R. microplus
adopting adult immersion test. For validation of DC, the resistance status was
checked in seven tick isolates of R. microplus collected from northern and
eastern regions of India. The RR50 and RR95 values of the field isolates against
ivermectin were determined and were in the range of 1.56-8.25 and 1.93-27.58,
respectively. All the collected isolates were found to have higher lethal
concentration and resistance ratio in comparison to reference susceptible IVRI-1
tick line (LC50 = 21.68, LC95 = 46.77 ppm, RR = 1.0). Amongst the field isolates,
the isolate collected from Fatehgarh Sahib district (FTG) of Punjab state showed
highest RR50 of 8.25 indicating high level of resistance to IVM. The generated DC
will be used for IVM resistance characterization of ticks infesting cattle in
different parts of the country.
PMID- 29329622
TI - Prevalence and molecular characterization of Giardia duodenalis in cattle and
sheep from the Qinghai-Tibetan Plateau Area (QTPA), northwestern China.
AB - Giardia duodenalis is an important intestinal protozoan parasite with a wide
range of hosts, including humans, livestock and wildlife. The purpose of this
study was to determine the prevalence of G. duodenalis infections among cattle
and sheep in the Qinghai-Tibetan Plateau Area (QTPA) and to assess the potential
risk of the zoonotic transmission of this pathogen. A total of 454 stool
specimens were collected and examined using the nested PCR method based on the G.
duodenalis SSUrRNA gene fragment. Thirty-nine out of 389 cattle specimens
examined were positive (10%) for the G. duodenalis infection. After the sequence
analysis of the SSUrRNA gene, all detected G. duodenalis belong to assemblage E.
No G. duodenalis infections were found in the 65 investigated samples from sheep.
Our data therefore indicates that G. duodenalis is a common parasite in cattle in
the QTPA, China and that cattle appear to be a reservoir of G. duodenalis for
other animals and the environmental water supplies in the area.
PMID- 29329623
TI - Parasite control strategies used by equine owners in the United States: A
national survey.
AB - The widespread occurrence of anthelmintic resistance in equine parasites across
the world has led to recommendations of fecal egg count-based parasite programs
to reduce treatment intensity and thereby delay further development of resistance
as much as possible. The most recent study describing equine parasite control in
the United States was conducted 20 years ago, and little is known about current
strategies employed. This study was part of the National Animal Health Monitoring
Systems (NAHMS) Equine 2015 Study, and aimed to describe equine parasite control
strategies in the U.S. and evaluate to which extent respondents were in
compliance with current guidelines. The study was carried out in 28 states,
representing 70.9% of all equine operations with at least five equids present.
Two questionnaires were administered, either by mail or delivered in person by
veterinary medical officers. Participants provided specific details of their
operation and were asked questions about strategies for anthelmintic therapy and
diagnostic testing. A total of 380 operations provided data regarding their
parasite control practices. Most respondents dewormed 2-3 times a year with
ivermectin being the most commonly used anthelmintic. About 22% of respondents
used fecal egg counts (FEC) in some form, with less than 10% using them on a
regular basis. Less than 5% made use of fecal egg count reduction tests (FECRT).
These results suggest little change since the last nationwide survey was
conducted in 1998, as the majority of respondents did not report using FECs. This
is in stark contrast to recent European surveys, where 50-60% of respondents were
using FECs routinely. However, the anthelmintic treatment intensity appears to
have been lowered compared to 1998. Taken together, these results suggest a
continuing need for education and outreach regarding sustainable parasite
control.
PMID- 29329624
TI - Apparent prevalence of and risk factors for infection with Ostertagia ostertagi,
Fasciola hepatica and Dictyocaulus viviparus in Swiss dairy herds.
AB - Infections with helminth parasites can negatively affect performance of dairy
cows. Knowledge on infection intensity, spatial distributions and risk factors
are key to develop targeted treatment strategies. Canada and most EU countries
have conducted large investigations, but respective data for Switzerland were
missing. We now performed a bulk tank milk serosurvey for Ostertagia ostertagi,
Fasciola hepatica, and Dictyocaulus viviparus on a total of 1036 voluntarily
participating dairy herds that were sampled at confinement periods, i.e. in
winter 2014/15 or 2015/16, respectively. All samples were analyzed with
commercial ELISAs for antibodies (AB) against O. ostertagi and F. hepatica, and
those of the first sampling period additionally with an in-house ELISA for AB
against D. viviparus. Testing for the latter parasite was not done in the second
year of the study, as the sampling period might have missed infections due to the
short lived nature of specific antibodies. The possible influence of geographic,
climatic, and farm management variables on AB levels were assessed for each
parasite using scanning cluster and multiple regression analysis. Overall
seroprevalence for O. ostertagi was 95.5% (95% C.I.: 94.0-96.6), with a mean
optical density ratio (ODR) of 0.83, for F. hepatica 41.3% (95% C.I.: 38.3-44.4),
and for D. viviparus 2.9% (95% C.I.: 1.6-4.7). There were no significant
differences between the two sampling periods. For all parasites, significant
geographic clusters of higher AB levels could be established. Furthermore, AB
levels against all three parasites were positively correlated with each other,
indicating either cross-reactions or co-infections. For O. ostertagi, herd size
and percentage of pasture in the ration were positively correlated with AB
levels. For F. hepatica, altitude above sea level (a.s.l.) positively, and milk
production per cow and year was negatively correlated with AB levels. This work
provides baseline data for further studies performing in-depth risk factor
analysis and investigating management as well as targeted treatment options to
control the parasites.
PMID- 29329625
TI - Immune development and performance characteristics of Romney sheep selected for
either resistance or resilience to gastrointestinal nematodes.
AB - Immunological and performance characteristics were explored in Romney sheep from
lines selected for either resistance or resilience to parasite infection. At a
mean 78 days-of-age, twin lambs from a line selected for resistance (RT) and
lambs from a line selected for resilience (RL) were infected with the intestinal
nematode Trichostrongylus colubriformis for 100 days (I) while their twin
remained as an uninfected control (C). Compared with RL, RT animals had lower
levels of circulating CD4+ T-cells (P = 0.003) but a greater proportion of these
were activated (CD4+CD25+) in response to infection (P = 0.007). Differences
between the lines in humoral immune responses to nematode infection varied with
higher levels of T. colubriformis specific immunoglobulin (Ig) E in RT-I than RL
I (P = 0.002) but similar levels of both IgG (P = 0.926) and IgA (P = 0.321)
responses. Temporal differences in the immune response also existed between the
lines with RT-I animals displaying an earlier peak and more rapid reduction in
FEC and an earlier peak in T. colubriformis specific IgA. In addition, compared
with their RT-C and RL-C counterparts, infection caused a 22% reduction in feed
intake from day 56 (P = 0.001) with total feed intake reduced by 15% and 9% for
RT-I and RL-I, respectively. Cumulative liveweight gain was greatest for RL
animals (P = 0.026) and relative to RT-C and RL-C was reduced by 5.8 kg and 4.9
kg for RT-I and RL-I, respectively. Overall, the selection lines appear to have
differences in immunological characteristics that are both dependent on, and
independent of parasite infection. Further, the difference in growth in the
uninfected animals coupled with the similar cost of infection suggests the lower
liveweight gain of RT-I compared with RL-I may be due to inherent differences
between the lines in their growth potential, rather than a greater cost of
infection in animals selected for resistance.
PMID- 29329626
TI - Applicability of FLOTAC(r) technique in recovering equine strongyle larvae in the
pasture: A comparison study.
AB - The FLOTAC(r) technique represents a highly sensitive method for the isolation of
oocysts, eggs, and larvae of parasites in faeces. This assay could be used for
detecting free-living stages of nematodes in the pasture but no attempt has been
assessed so far. Therefore, the performance of FLOTAC(r) technique for isolating
infective larvae of nematodes in the environment was investigated and compared
with the spontaneous sedimentation (SST) and centrifugal sedimentation (CST)
techniques. The study was conducted in a horse farm located in northeastern
Brazil, where the occurrence of strongyle larvae had been previously reported.
Pasture samplings were collected monthly from January to May 2016 in a 376 m2
crop area harvested with the Guinea grass Panicum cultivar Massai. The recovery
of third-stage larvae (L3) was performed using the FLOTAC(r), SST and CST
techniques. Values of Cohen's kappa coefficient, sensitivity, specificity,
positive and negative predictive values, and accuracy of each technique were
assessed. Although strongyle larvae were evenly detected, with the FLOTAC(r)
technique yielded the highest number of positive samples (i.e., 41%, 41/100, p <
.0001). The main parasites isolated belonged to the Cyathostominae and
Strongylinae subfamilies. Based on these results, the FLOTAC(r) technique should
be considered as practical and safe method for the isolation of nematode larvae
in the pasture, thus opening a new potential use for this tool in the field.
PMID- 29329627
TI - Comparative efficacy of curcumin and paromomycin against Cryptosporidium parvum
infection in a BALB/c model.
AB - Cryptosporidium is a ubiquitous protozoan parasite causing gastrointestinal
disorder in various hosts worldwide. The disease is self-limiting in the
immunocompetent but life-threatening in immunodeficient individuals.
Investigations to find an effective drug for the complete elimination of the
Cryptosporidium infection are ongoing and urgently needed. The current study was
undertaken to examine the anti-cryptosporidial efficacy of curcumin in
experimentally infected mice compared with that of paromomycin. Oocysts were
isolated from a pre-weaned dairy calf and identified as Cryptosporidium parvum
using a nested- polymerase chain reaction (PCR) on Small subunit ribosomal
ribonucleic acid (SSU rRNA) gene and sequencing analysis. One hundred and ten
female BALB/c mice were divided into five groups. Group 1 was infected and
treated with curcumin; Group 2 infected and treated with paromomycin; Group 3
infected without treatment; Group 4 included uninfected mice treated with
curcumin, and Group 5 included uninfected mice treated with distilled water for
11 successive days, starting on the first day of oocyst shedding. The oocyst
shedding was recorded daily. At days 0, 3, 7, and 11 of post treatments, five
mice from each group were killed humanly; jejunum and ileum tissue samples were
processed for histopathological evaluation and counting of oocyst on villi,
simultaneously. Furthermore, total antioxidant capacity (TAC) and malondialdehyde
(MDA) concentrations in affected tissues were also measured in different groups.
By treatments, tissue lesions and the number of oocyst on villi of both jejunum
and ileum were decreased with a time-dependent manner. In comparison with Group
3, oocyst shedding was stopped at the end of treatment period in both groups 1
and 2 without recurrence at 10days after drug withdrawal. Also, TAC was increased
and the MDA concentrations were decreased in Group 1. Moreover, paromomycin
showed acceptable treatment outcomes during experiment and its anti
cryptosporidial activity was faster than curcumin. The results confirmed the anti
cryptosporidial and antioxidant activity of curcumin against C. parvum and
further evaluation of immunosuppressed animal models needs to be carried out.
PMID- 29329628
TI - Spirocerca lupi induced oesophageal neoplasia: Predictors of surgical outcome.
AB - Canine spirocercosis is caused by the nematode Spirocerca lupi. Migration results
in oesophageal fibro-inflammatory nodules that may undergo neoplastic
transformation. No studies have assessed pre- or post-surgical prognostic
indicators in dogs that undergo intervention for S. lupi induced oesophageal
neoplasia. This observational, multi-center study aimed to assess the outcome of
dogs with Spirocerca induced sarcoma undergoing endoscopic-guided ablation (n =
12) or surgery (n = 18), and identify prognostic indicators. Parameters evaluated
included: age, weight, gender, presenting complaints, duration of clinical signs,
complete blood count, serum biochemistry, neoplasia size, placement of
percutaneous endoscopically-placed gastrostomy tube, histopathological mitotic
indices, days to discharge and chemotherapy administration. Kaplan-Meier survival
curves showed no difference in survival between ablation and surgery {(median:
73.5 days (range: 0-1511) vs. 108 days (range: 0-1550), respectively (p =
0.982)}. Reduced survival was documented in patients presenting with weight loss
(P = 0.027), hypochromasia (MCHC <33 g/dL, P = 0.023) or leucocytosis (>15 *
109/L, P = 0.017) with a hazard ratio of 2.51 (CI95% = 1.071-6.018, P = 0.034),
2.71 (CI95% = 1.10-6.65, P = 0.03) and 4.39 (CI95%: 1.21-15.97, P = 0.025)
respectively. In the dogs surviving more than 21 days, Ht <36% and leucocytosis
>15.0 * 109/L at presentation were associated with reduced survival (p = 0.016, p
= 0.021 respectively) and hazard ratio of 3.29 (CI95% = 1.18-9.2, P = 0.023) and
3.81 (CI95% = 1.15-12.55, P = 0.028) respectively. Intra-intervention-group
survival analysis identified increased survival time in dogs receiving
chemotherapy, but only within the surgical group (P = 0.02).The hospitalisation
time of dogs undergoing ablation (median: 0 days, range: 0-4) was significantly
shorter than dogs undergoing surgery (9 days, 1-21) (P < 0.001). In this study,
no clear benefit was identified for surgery, thus when ablation is technically
possible it should be considered advantageous, as hospitalisation time is
significantly shorter. Weight loss, hypochromasia and leucocytosis were
identified as long-term prognostic indicators at presentation.
PMID- 29329629
TI - Estimates of repeatability and correlations of hemoparasites infection levels for
cattle reared in endemic areas for Rhipicephalus microplus.
AB - Rhipicephalus microplus is a vector of cattle tick fever, a disease caused by the
protozoans Babesia bovisand B. bigemina, and also anaplasmosis, produced by the
Rickettsiales Anaplasma marginale. These tick-borne pathogens cause considerable
losses to Brazilian livestock breeders and represent an obstacle to the expanded
use of taurine breeds due to their higher sensitivity to ticks and hemoparasites
compared to zebu breeds. Differences in the susceptibility to hemoparasites were
also verified within breeds, suggesting that may be possible to select a most
resistant phenotype. Therefore, repeatability of R. microplus counts and copy
number of hemoparasites DNA were estimated, along with correlations between
themselves, aiming to verify if those measures can be used as parameters to
classify animals according to their parasite resistance degrees. Forty-two
Canchim females kept on pastures naturally infested by ticks were evaluated for
the level of infestation by R. microplus and infection by B. bovis, B. bigemina,
and A. marginale. Twenty-four evaluations were performed once a month, for adult
female ticks counts and blood samplings. The experimental period was divided into
four phases, according to the animals age range: Phase 1: 8 to 13 months
(collections 1 to 6); phase 2: 14 to 19 months (collections 7 to 12); phase 3: 20
to 25 months (collections 13 to 18), and phase 4: 26 to 31 months (collections 19
to 24). Blood samples were submitted to absolute quantification of hemoparasites
DNA sequences using qPCR. The hemoparasite and tick counts data were transformed
for normalization and were analyzed using mixed models. Among three species of
hemoparasites studied, A. marginale presented the highest level of infection.
During phase 3, B. bigemina presented higher infection levels (p < 0.05) compared
to B. bovis, whereas no differences were observed in other phases. Estimated
repeatabilities for parasite infection levels varied from low to moderate during
our experiment. There were low correlations between tick counts and parasite
infection levels, and between parasite infection levels from different species by
themselves. Based on these results, under conditions of the present study, we
suggest that it is possible to identify animals presenting a most resistant
phenotype against infection by both hemoparasites and ticks. Moreover, the animal
age may be an important factor related to resistance against these pathogens. The
data obtained shed more light on the resistance to hemoparasites studied.
PMID- 29329630
TI - Reply.
PMID- 29329631
TI - Comments on: Walsh and Tobias, "Low-Pressure Pericardial Tamponade: Case Report
and Review of the Literature".
PMID- 29329633
TI - Pediatric Adnexal Torsion: Not Just a Postmenarchal Problem.
PMID- 29329634
TI - Pediatric Adnexal Torsion.
PMID- 29329635
TI - Converting the Easy Internal Jugular (IJ) to a Central Line.
PMID- 29329636
TI - The Unique Environmental Influences of Acute Care Settings on Patient and
Physician Well-Being: A Call to Action.
PMID- 29329638
TI - Role of the IL-33/ST2L axis in colorectal cancer progression.
AB - Interleukin-33 (IL-33) has been identified as a natural ligand of ST2L. IL-33
primarily acts as a key regulator of Th2 responses through binding to ST2L, which
is antagonized by soluble ST2 (sST2). The IL-33/ST2L axis is involved in various
inflammatory pathologies, including ulcerative colitis (UC). Several recent
investigations have also suggested that the IL-33/ST2L axis plays a role in
colorectal cancer (CRC) progression. In CRC, tumor- and stroma-derived IL-33 may
activate ST2L on various cell types in an autocrine and paracrine manner.
Although several findings support the hypothesis that the IL-33/ST2L axis
positively regulates CRC progression, other reports do not; hence, this
hypothesis remains controversial. At any rate, recent studies have provided
overwhelming evidence that the IL-33/ST2L axis plays important roles in CRC
progression. This review summarizes the role of the IL-33/ST2L axis in the UC and
CRC microenvironments.
PMID- 29329639
TI - Vestibular stimulation makes people more egocentric.
PMID- 29329637
TI - Transcriptomic evidence of immune activation in macroscopically normal-appearing
and scarred lung tissues in idiopathic pulmonary fibrosis.
AB - Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease manifested by overtly
scarred peripheral and basilar regions and more normal-appearing central lung
areas. Lung tissues from macroscopically normal-appearing (IPFn) and scarred
(IPFs) areas of explanted IPF lungs were analyzed by RNASeq and compared with
healthy control (HC) lung tissues. There were profound transcriptomic changes in
IPFn compared with HC tissues, which included elevated expression of numerous
immune-, inflammation-, and extracellular matrix-related mRNAs, and these changes
were similar to those observed with IPFs compared to HC. Comparing IPFn directly
to IPFs, elevated expression of epithelial mucociliary mRNAs was observed in the
IPFs tissues. Thus, despite the known geographic tissue heterogeneity in IPF, the
entire lung is actively involved in the disease process, and demonstrates
pronounced elevated expression of numerous immune-related genes. Differences
between normal-appearing and scarred tissues may thus be driven by deranged
epithelial homeostasis or possibly non-transcriptomic factors.
PMID- 29329640
TI - Capturing real-life forgetting in transient epileptic amnesia via an incidental
memory test.
AB - Transient epileptic amnesia (TEA) is an epileptic syndrome characterized by
recurrent, brief episodes of amnesia. Patients with TEA often complain of
interictal (between attacks) retention deficits, characterised by an
'evaporation' of memories for recent events over days to weeks. Clinical tests of
anterograde memory often fail to corroborate these complaints as TEA patients
commonly perform within the normal range after the standard 10-30-min delay
period. Modified laboratory tests that include a 1-3 week delay period frequently
reveal clear evidence of 'accelerated long-term forgetting' (ALF). However, they
are not used routinely and lack ecological validity. In the present study we
examined whether 'real-life' ALF can be captured via a controlled incidental
memory test in TEA patients. To this end, the experimenter told 27 TEA patients
and 32 controls a well-rehearsed amusing story, apparently as a way of making
light conversation before starting a set of research experiments. Without prior
warning, the experimenter subsequently probed the participants' memory of this
story via tests of free recall and forced choice recognition after 30 min or 1
week. After 30 min retention was comparable in TEA patients and controls. After 1
week TEA patients retained significantly less story material than controls, and
significant ALF was revealed in the TEA patients in the recognition test. Our
data show that ALF in a 'real-life' situation can occur even when standard memory
tests indicate normal memory function. Moreover, our data suggest that incidental
memory tests can capture real-life ALF, and that forced-choice recognition tests
might be more sensitive than free recall tests for the detection of real-life
ALF.
PMID- 29329641
TI - Discussion of "Nonatherosclerotic vascular causes of acute abdominal pain".
PMID- 29329643
TI - IgA nephropathy and IgA vasculitis with nephritis have a shared feature involving
galactose-deficient IgA1-oriented pathogenesis.
AB - Galactose-deficient IgA1 has been proposed as an important effector molecule in
IgA nephropathy (IgAN). We previously showed that the galactose-deficient IgA1
specific monoclonal antibody KM55 can detect circulating galactose-deficient IgA1
in patients with IgAN, enabling us to study the molecular roles of galactose
deficient IgA1. Herein, we further examined the pathophysiological significance
of galactose-deficient IgA1 in glomerular deposits of patients with IgAN by
immunohistochemistry using KM55. Immunostaining of galactose-deficient IgA1 with
KM55 was performed in paraffin-embedded sections of renal biopsy specimens from
48 patients with IgAN and 49 patients with other renal diseases such as lupus
nephritis, HCV-related nephropathy, IgA vasculitis with nephritis (IgA-VN), and
membranous nephropathy. Glomerular galactose-deficient IgA1 was specifically
detected in IgAN and IgA-VN but not in the other renal diseases. Galactose
deficient IgA1 was localized predominantly in the mesangial region as IgA
deposition. However, galactose-deficient IgA1 was not detected in patients with
lupus nephritis accompanied by glomerular IgA deposition. Thus, our study
strongly suggests that IgAN and IgA-VN have a shared feature regarding galactose
deficient IgA1-oriented pathogenesis.
PMID- 29329644
TI - Anticancer carbazole alkaloids and coumarins from Clausena plants: A review.
AB - Pharmaceutical research has focused on the discovery and development of
anticancer drugs. Clinical application of chemotherapy drugs is limited due to
their severe side effects. In this regard, new naturally occurring anticancer
drugs have gained increasing attention because of their potential effectiveness
and safety. Fruits and vegetables are promising sources of anticancer remedy.
Clausena (family Rutaceae) is a genus of flowering plants and includes several
kinds of edible fruits and vegetables. Phytochemical and pharmacological studies
show that carbazole alkaloids and coumarins from Clausena plants exhibit
anticancer activity. This review summarizes research progresses made in the
anticancer properties of plants belonging to Clausena; in particular, compounds
with direct cytotoxicity, cell cycle arrest, apoptosis induction, and immune
potentiation effects are discussed. This review reveals the potential use of
plants from Clausena in preventing and treating cancer and provides a basis for
development of relevant therapeutic agents.
PMID- 29329642
TI - Mesenchymal stem cell-macrophage crosstalk and bone healing.
AB - Recent research has brought about a clear understanding that successful fracture
healing is based on carefully coordinated cross-talk between inflammatory and
bone forming cells. In particular, the key role that macrophages play in the
recruitment and regulation of the differentiation of mesenchymal stem cells
(MSCs) during bone regeneration has been brought to focus. Indeed, animal studies
have comprehensively demonstrated that fractures do not heal without the direct
involvement of macrophages. Yet the exact mechanisms by which macrophages
contribute to bone regeneration remain to be elucidated. Macrophage-derived
paracrine signaling molecules such as Oncostatin M, Prostaglandin E2 (PGE2), and
Bone Morphogenetic Protein-2 (BMP2) have been shown to play critical roles;
however the relative importance of inflammatory (M1) and tissue regenerative (M2)
macrophages in guiding MSC differentiation along the osteogenic pathway remains
poorly understood. In this review, we summarize the current understanding of the
interaction of macrophages and MSCs during bone regeneration, with the emphasis
on the role of macrophages in regulating bone formation. The potential
implications of aging to this cellular cross-talk are reviewed. Emerging
treatment options to improve facture healing by utilizing or targeting MSC
macrophage crosstalk are also discussed.
PMID- 29329645
TI - Polysaccharides extracted from the roots of Bupleurum chinense DC modulates
macrophage functions.
AB - The present study aimed to investigate the effects of polysaccharides extracted
from Bupleurum chinense DC (BCPs) on macrophage functions. In the in vivo
experiment, 1 mL of 5% sodium thioglycollate was injected into the abdomen of the
mice on Day 0 and macrophages were harvested on Day 4. The macrophages were
cultured in plates and treated with different concentrations of BCPs and
stimulus. Effects of BCPs on macrophage functions were assessed by chemotaxis
assay, phagocytosis assay and Enzyme-Linked Immunosorbent Assay (ELISA). Our
results showed the enhanced chemotaxis, phagocytosis and secretion of nitric
oxide (NO) and inflammatory cytokines by macrophages when treated with BCPs.
However, when chemotaxis and phagocytosis were up-regulated by complement
components or opsonized particles, BCPs inhibited these effects. Also, the NO
production induced by lipopolysaccharides (LPS) was suppressed by BCPs mildly.
Moreover, BCPs had an inhibitory effect on the [Ca2+]i elevation of macrophages.
These results suggested that BCPs exerted modulatory effects on macrophage
functions, which may contribute to developing novel approaches to treating
inflammatory diseases.
PMID- 29329646
TI - Effects of Gardenia jasminoides extracts on cognition and innate immune response
in an adult Drosophila model of Alzheimer's disease.
AB - Herbal extracts have been extensively used worldwide for their application on
memory improvement, especially among aged and memory-deficit populations. In the
present study, the memory loss induced by human Abeta protein over-expression in
fruitfly Alzheimer's disease (AD) model was rescued by multiple extracts from
Gardenia jasminoides. Three extracts that rich with gardenia yellow, geniposide,
and gardenoside components showed distinct rescue effect on memory loss. Further
investigation on adding gardenoside into a formula of Ganoderma lucidum, Panax
notoginseng and Panax ginseng (GPP) also support its therapeutic effects on
memory improvement. Interestingly, the application of GPP and gardenoside did not
alter the accumulation of Abeta proteins but suppressed the expression of immune
related genes in the brain. These results revealed the importance and relevancy
of anti-inflammation process and the underlying mechanisms on rescuing memory
deficits, suggesting the potential therapeutic use of the improved GPP
formulation in improving cognition in defined population in the future.
PMID- 29329647
TI - Atractylodes lancea rhizome water extract reduces triptolide-induced toxicity and
enhances anti-inflammatory effects.
AB - The present study was designed to explore the influence of water extracts of
Atractylodes lancea rhizomes on the toxicity and anti-inflammatory effects of
triptolide (TP). A water extract was prepared from A. lancea rhizomes and co
administered with TP in C57BL/6 mice. The toxicity was assayed by determining
serum biochemical parameters and visceral indexes and by liver histopathological
analysis. The hepatic CYP3A expression levels were detected using Western
blotting and RT-PCR methods. The data showed that the water extract of A. lancea
rhizomes reduced triptolide-induced toxicity, probably by inducing the hepatic
expression of CYP3A. The anti-inflammatory effects of TP were evaluated in mice
using a xylene-induced ear edema test. By comparing ear edema inhibition rates,
we found that the water extract could also increase the anti-inflammatory effects
of TP. In conclusion, our results suggested that the water extract of A. lancea
rhizomes, used in combination with TP, has a potential in reducing TP-induced
toxicity and enhancing its anti-inflammatory effects.
PMID- 29329648
TI - Preparation and physicochemical characterization of T-OA PLGA microspheres.
AB - As the carrier of water-insoluble drugs, microspheres can play a role in
increasing solubility and delaying releasing essence. The objective of this study
was to improve the solubility and to delay the release of a newly discovered
antitumor compound 3beta-hydroxyolea-12-en-28-oic acid-3, 5, 6-trimethylpyrazin-2
methyl ester (T-OA). Early-stage preparation discovery concept (EPDC) was
employed in the present study. The preparation, physicochemical characterization,
and drug release properties of PLGA microspheres were evaluated. T-OA-loaded PLGA
microspheres were prepared by an oil-in-water (O/W) emulsification solvent
evaporation method. Characterization and release behaviors of the T-OA PLGA
microspheres were evaluated by X-ray diffract (XRD), differential scanning
calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), scanning
electron microscopy (SEM), and high performance liquid chromatography (HPLC). The
results demonstrated that T-OA-loaded PLGA microspheres could be successfully
obtained through solvent evaporation method with appropriate morphologic
characteristics and high encapsulation efficiency. The XRD analysis showed that T
OA would be either molecularly dispersed in the polymer or distributed in an
amorphous form. The DSC and FTIR analysis proved that there were interactions
between T-OA and PLGA polymer. SEM observations displayed the morphology of the
microspheres was homogeneous and the majority of the spheres ranged between 50
and 150 MUm. The drug release behavior of the microspheres in the phosphate
buffered saline medium exhibited a sustained release and the duration of the
release lasted for more than 23 days, which was fit with zero-order release
pattern with r2 = 0.9947. In conclusion, TOA-loaded PLGA microspheres might hold
great promise for using as a drug-delivery system in biomedical applications.
PMID- 29329649
TI - HPPR encodes the hydroxyphenylpyruvate reductase required for the biosynthesis of
hydrophilic phenolic acids in Salvia miltiorrhiza.
AB - Salvia miltiorrhiza is a medicinal plant widely used in the treatment of
cardiovascular and cerebrovascular diseases. Hydrophilic phenolic acids,
including rosmarinic acid (RA) and lithospermic acid B (LAB), are its primary
medicinal ingredients. However, the biosynthetic pathway of RA and LAB in S.
miltiorrhiza is still poorly understood. In the present study, we accomplished
the isolation and characterization of a novel S. miltiorrhiza
Hydroxyphenylpyruvate reductase (HPPR) gene, SmHPPR, which plays an important
role in the biosynthesis of RA. SmHPPR contained a putative catalytic domain and
a NAD(P)H-binding motif. The recombinant SmHPPR enzyme exhibited high HPPR
activity, converting 4-hydroxyphenylpyruvic acid (pHPP) to 4-hydroxyphenyllactic
acid (pHPL), and exhibited the highest affinity for substrate 4
hydroxyphenylpyruvate. SmHPPR expression could be induced by various treatments,
including SA, GA3, MeJA and Ag+, and the changes in SmHPPR activity were
correlated well with hydrophilic phenolic acid accumulation. SmHPPR was localized
in cytoplasm, most likely close to the cytosolic NADPH-dependent hydroxypyruvate
reductase active in photorespiration. In addition, the transgenic S. miltiorrhiza
hairy roots overexpressing SmHPPR exhibited up to 10-fold increases in the
products of hydrophilic phenolic acid pathway. In conclusion, our findings
provide a new insight into the synthesis of active pharmaceutical compounds at
molecular level.
PMID- 29329650
TI - Synthesis and anti-hepatocellular carcinoma activity of novel O2-vinyl
diazeniumdiolate-based nitric oxide-releasing derivatives of oleanolic acid.
AB - Considering that high levels of nitric oxide (NO) exert anti-cancer effect and
the derivatives of oleanolic acid (OA) have shown potent anti-cancer activity,
new O2-vinyl diazeniumdiolate-based NO releasing derivatives (5a-l, 11a-l) of OA
were designed, synthesized, and biologically evaluated in the present study.
These derivatives could release different amounts of NO in liver cells. Among
them, 5d, 5i, 5j, 11g, 11h, and 11j released more NO in SMMC-7721 cells and
displayed stronger proliferative inhibition against SMMC-7721 and HepG2 cells
than OA and other tested compounds. The most active compound 5j showed almost 20
fold better solubility than OA in aqueous solution, released larger amounts of NO
in liver cancer cells than that in normal ones, and exhibited potent anti
hepatocellular carcinoma activity but little effect on the normal liver cells.
The inhibitory activity against the cancer cells was significantly diminished
upon addition of an NO scavenger, suggesting that NO may contribute, at least in
part, to the activity of 5j.
PMID- 29329651
TI - Lignans and diterpenes isolated from Tirpitzia ovoidea and their biological
activities.
AB - A new lignan, tirpitzin A (17) together with 20 known compounds (1-16, and 18-21)
were isolated from the ethyl acetate soluble fraction of ethanol extract of the
aerial parts of Tirpitzia ovoidea. The structure of new compound was elucidated
by means of spectroscopic analysis. Of the known compounds, 7-21 were isolated
from Linaceae family for the first time. The pharmacological activity of the
crude extracts was tested using a mouse inflammation model induced by dimethyl
benzene. The results demonstrated that the ethyl acetate soluble fraction had
anti-inflammatory activity. Moreover, the cytotoxic and anti-inflammatory
activities of some compounds were studied. The new compound 17 showed moderate
cytotoxic effect against BxPC-3 cell line (IC50 = 19.51MUmol.L-1) and Compound 10
showed significant cytotoxicity against HepG2, HL-60, U87 and BxPC-3 cell lines
with IC50 values in the range 4.2-8.3MUmol.L-1. Additionally, Compounds 2, 10,
11, and 13 exhibited potent inhibitory effects on LPS-induced nitric oxide
production in RAW 264.7 macrophages at the concentration of 50MUmol.L-1.
PMID- 29329652
TI - Three new anthraquinone derivatives isolated from Symplocos racemosa and their
antibiofilm activity.
AB - Three new alkyl substituted anthraquinone derivatives, trivially named as
symploquinones A-C (Compounds 1-3) were isolated from Symplocos racemosa. The
structures of these compounds were determined on the basis of extensive
spectroscopic analyses (UV, IR, Mass, 1H- and 13C-NMR, and two-dimensional (2D)
NMR techniques). The resulting data were also compared with the reported
literature. These compounds were then subjected to antibacterial or antibiofilm
testing. Compounds 1 and 3 exhibited good antibacterial activity in the
concentration range of 160-83 MUg.mL-1 against Streptococcus mutans, methicillin
resistant Staphylococcus aureus and Proteus mirabilis. Both compounds were
further screened for anti-biofilm activity, which revealed promising activities
at sub-MIC concentrations. None of the compounds were found to be active against
Klebsiella pneumoniae.
PMID- 29329653
TI - Cycloartane triterpenoid and its glucoside isolated from Cassia occidentalis.
AB - In the present study, one new cycloartane triterpenoid, named cycloccidentalic
acid C (1) and its glucoside, cycloccidentaliside VI (2) were isolated from the
whole plant of Cassia occidentalis. Their structures were elucidated by a
combinational analyses of 1D and 2D NMR data and HRMS. Compound 2 showed modest
anti-HIV-1 activity with EC50 value of 1.44 MUmol.L-1 and TI (Therapeutic Index)
value of 15.59.
PMID- 29329654
TI - UHPLC-LTQ-Orbitrap-based metabolomics coupled with metabolomics pathway analysis
method for exploring the protection mechanism of Kudiezi injection in a rat anti
ischemic cerebral reperfusion damage model.
AB - Kudiezi injection has been used extensively in the treatment of cerebrovascular
and cardiovascular diseases. However, its therapeutic effects and underlying
mechanism of action are not fully understood. The aim of the present study was to
clarify the protective mechanisms of Kudiezi injection on cerebral ischemic
injury, using metabolomics methods. Middle cerebral artery occlusion (MCAO) was
introduced in rats to build the cerebral ischemic damage. UHPLC-LTQ-Orbitrap
based analytical method was established for analysis of the metabolites. The raw
mass data of all samples were normalized with Sieve 2.2 software and then
introduced to orthogonal partial least squares discriminant analysis (OPLS-DA)
model. Finally, 23 metabolites in plasma (15 were tentatively identified) were
chosen as potential biomarkers, according to accurate mass measurements (< 5
ppm), MS/MS fragmentation patterns, and diagnostic product ions. Furthermore, on
the basis of metabolic pathway analysis via metabolomics pathway analysis
(MetPA), we first discovered that the protection mechanism in anti-ischemic
cerebral reperfusion damage of Kudiezi injection was possibly related to the
biosynthesis of phenylalanine, tyrosine, and tryptophan. The present study
provided a useful approach for exploring the mechanism of ischemic stroke and
evaluating the efficacy of Kudiezi injection or other traditional medicines.
PMID- 29329655
TI - [Erratum to "Cervical lift: An update" [Annales de chirurgie plastique esthetique
2017;62:461-73. DOI: 10.1016/j.anplas.2017.08.002]].
PMID- 29329656
TI - Techno-economic performance indicators of municipal solid waste collection
strategies.
AB - Several indicators for the evaluation of the MSW collection systems have been
proposed in the literature. These evaluation tools consider only some of the
aspects that influence the operational efficiency of the collection service. The
aim of this paper is to suggest a set of (easy to calculate) indicators that
overcomes this limitation, taking into account both the characteristics of
collected waste and the operational - economic performance. The main components
of the collection system (labour, vehicles and containers) are separately
considered so that it is possible to quantify and compare their role within the
whole process. As an example of application, the proposed approach was used for
comparing the MSW collection strategies adopted in four towns in Northern Italy.
Results are discussed and a comparison with alternative assessment methods
available in the scientific literature is reported.
PMID- 29329657
TI - The development and trial of an unmanned aerial system for the measurement of
methane flux from landfill and greenhouse gas emission hotspots.
AB - This paper describes the development of a new sampling and measurement method to
infer methane flux using proxy measurements of CO2 concentration and wind data
recorded by Unmanned Aerial Systems (UAS). The flux method described and trialed
here is appropriate to the spatial scale of landfill sites and analogous
greenhouse gas emission hotspots, making it an important new method for low-cost
and rapid case study quantification of fluxes from currently uncertain (but
highly important) greenhouse gas sources. We present a case study using these UAS
based measurements to derive instantaneous methane fluxes from a test landfill
site in the north of England using a mass balance model tailored for UAS sampling
and co-emitted CO2 concentration as a methane-emission proxy. Methane flux (and
flux uncertainty) during two trials on 27 November 2014 and 5 March 2015, were
found to be 0.140 kg s-1 (+/-61% at 1sigma), and 0.050 kg s-1 (+/-54% at 1sigma),
respectively. Uncertainty contributing to the flux was dominated by ambient
variability in the background (inflow) concentration (>40%) and wind speed
(>10%); with instrumental error contributing only ~1-2%. The approach described
represents an important advance concerning the challenging problem of greenhouse
gas hotspot flux calculation, and offers transferability to a wide range of
analogous environments. This new measurement solution could add to a toolkit of
approaches to better validate source-specific greenhouse emissions inventories -
an important new requirement of the UNFCCC COP21 (Paris) climate change
agreement.
PMID- 29329659
TI - Discovery of Mcl-1 inhibitors based on a thiazolidine-2,4-dione scaffold.
AB - Inspired by a rhodanine-based dual inhibitor of Bcl-xL and Mcl-1, a focused
library of analogues was prepared wherein the rhodanine core was replaced with a
less promiscuous thiazolidine-2,4-dione scaffold. Compounds were initially
evaluated for their abilities to inhibit Mcl-1. The most potent compound 12b
inhibited Mcl-1 with a Ki of 155 nM. Further investigation revealed comparable
inhibition of Bcl-xL (Ki = 90 nM), indicating that the dual inhibitory profile of
the initial rhodanine lead had been retained upon switching the heterocycle core.
PMID- 29329658
TI - Novel compounds with potent CDK9 inhibitory activity for the treatment of
myeloma.
AB - Cyclin-dependent kinases (CDKs) and Polo-like kinases (PLKs) play key role in the
regulation of the cell cycle. The aim of our study was originally the further
development of our recently discovered polo-like kinase 1 (PLK1) inhibitors. A
series of new 2,4-disubstituted pyrimidine derivatives were synthesized around
the original hit, but their PLK1 inhibitory activity was very poor. However the
novel compounds showed nanomolar CDK9 inhibitory activity and very good
antiproliferative effect on multiple myeloma cell lines (RPMI-8226).
PMID- 29329660
TI - Cochlea CT radiomics predicts chemoradiotherapy induced sensorineural hearing
loss in head and neck cancer patients: A machine learning and multi-variable
modelling study.
AB - OBJECTIVES: Immediately or after head-and-neck (H&N) cancer chemoradiotherapy
(CRT), patients may undergone significant sensorineural hearing loss (SNHL) which
could affect their quality of life. Radiomic feature analysis is proposed to
predict SNHL induced by CRT. MATERIAL AND METHODS: 490 image features of 94
cochlea from 47 patients treated with three dimensional conformal RT (3DCRT) for
different H&N cancers were extracted from CT images. Different machine learning
(ML) algorithms and also least absolute shrinkage and selection operator (LASSO)
penalized logistic regression were implemented on radiomic features for feature
selection, classification and prediction. Also, LASSO penalized logistic model
was used for outcome modelling. RESULTS: The predictive power of ten ML methods
was more than 70% (in accuracy, precision and area under the curve of receiver
operating characteristic curve (AUC)). According to the LASSO penalized logistic
modelling, 10 of the 490 radiomic features selected as the associated features
with SNHL status. All of the 10 features were statistically associated with SNHL
(all of adjusted P-values < .001). CONCLUSION: CT radiomic analysis proposed in
this study, could help in the prediction of hearing loss induced by
chemoradiation. Our study also, demonstrates that combination of radiomic
features with clinical and dosimetric variables can model radiotherapy outcome
such as SNHL.
PMID- 29329661
TI - The Meshed Autologous Vein.
PMID- 29329662
TI - A Summation Analysis of Compliance and Complications of Compression Hosiery for
Patients with Chronic Venous Disease or Post-thrombotic Syndrome.
AB - OBJECTIVES: Compression stockings are commonly prescribed for patients with a
range of venous disorders, but are difficult to don and uncomfortable to wear.
This study aimed to investigate compliance and complications of compression
stockings in patients with chronic venous disease (CVD) and post-thrombotic
syndrome (PTS). METHODS: A literature search of the following databases was
carried out: MEDLINE (via PubMed), EMBASE (via OvidSP, 1974 to present), and
CINAHL (via EBSCOhost). Studies evaluating the use of compression stockings in
patients with CVD (CEAP C2-C5) or for the prevention or treatment of PTS were
included. After scrutinising full text articles, compliance with compression and
associated complications were assessed. Compliance rates were compared based on
study type and degree of compression. Good compliance was defined as patients
wearing compression stockings for >50% of the time. RESULTS: From an initial
search result of 4303 articles, 58 clinical studies (37 randomised trials and 21
prospective studies) were selected. A total of 10,245 limbs were included, with
compression ranging from 15 to 40 mmHg (not stated in 12 studies) and a median
follow-up of 12 months (range 1-60 months). In 19 cohorts, compliance was not
assessed and in a further nine, compliance was poorly specified. Overall, good
compliance with compression was reported for 5371 out of 8104 (66.2%) patients.
The mean compliance, weighted by study size, appeared to be greater for
compression <=25 mmHg (77%) versus > 25 mmHg (65%) and greater in the randomised
studies (74%) than in prospective observational studies (64%). Complications of
stockings were not mentioned in 43 out of 62 cohorts reviewed. Where
complications were considered, skin irritation was a common event. CONCLUSIONS:
In published trials, good compliance with compression is reported in around two
thirds of patients, with inferior compliance in those given higher degrees of
compression. Further studies are required to identify predictors of non
compliance, to help inform the clinical management of these patients.
Complications of compression are not documented in many studies and should be
given more consideration in the future.
PMID- 29329663
TI - Reintroducing Pazopanib Reverses the Primary Resistance of Nivolumab in a Patient
With Metastatic Clear-cell Renal Cell Carcinoma.
PMID- 29329664
TI - The impact of mental health disorders on 30-day readmission after bariatric
surgery.
AB - BACKGROUND: Mental health disorders are common among bariatric surgery patients.
Mental health disorders, particularly depression, have been associated with
poorer surgical outcomes, indicating the bariatric surgery patient population
warrants special clinical attention. OBJECTIVE: Our study sought to examine the
effect of diagnosed mental health disorders on 30-day readmission for those
undergoing bariatric surgery in hospitals across Pennsylvania from 2011 to 2014.
METHODS: We used Pennsylvania Healthcare Cost Containment Council data to perform
this analysis. Inclusion criteria encompassed patients aged>18 years who
underwent bariatric surgery at any hospital or freestanding surgical facility in
Pennsylvania between 2011 and 2014. Mental health disorders were identified using
predetermined International Classification of Disease, Ninth Revision codes.
Logistic regression was used to model the risk of 30-day readmission and estimate
the effect of mental health disorders on 30-day readmission. RESULTS: Of the
19,259 patients who underwent bariatric surgery, 40.3% had a diagnosed mental
health disorder; 6.51% of all patients were readmitted within 30 days. Patients
with a diagnosed mental health disorder had 34% greater odds of readmission (odds
ratio = 1.34, 95% confidence interval: 1.19-1.51) relative to patients with no
diagnosed mental health disorder. Patients with major depressive disorder/bipolar
disorder had 46% greater odds of being readmitted compared with patients with no
major depressive disorder/bipolar disorder diagnosis. CONCLUSION: Study findings
imply the need for risk assessment of patients before postoperative discharge.
Given that patients with mental health diagnoses are at increased risk of 30-day
readmission after bariatric surgery, they may benefit from additional discharge
interventions designed to attenuate potential readmissions.
PMID- 29329666
TI - Advances in self-healing materials based on vascular networks with mechanical
self-repair characteristics.
AB - Here, we review the state-of-the-art in the field of engineered self-healing
materials. These materials mimic the functionalities of various natural materials
found in the human body (e.g., the healing of skin and bones by the vascular
system). The fabrication methods used to produce these "vascular-system-like"
engineered self-healing materials, such as electrospinning (including co
electrospinning and emulsion spinning) and solution blowing (including coaxial
solution blowing and emulsion blowing) are discussed in detail. Further, a few
other approaches involving the use of hollow fibers are also described. In
addition, various currently used healing materials/agents, such as
dicyclopentadiene and Grubbs' catalyst, poly(dimethyl siloxane), and bisphenol-A
based epoxy, are described. We also review the characterization methods employed
to verify the physical and chemical aspects of self-healing, that is, the methods
used to confirm that the healing agent has been released and that it has resulted
in healing, as well as the morphological changes induced in the damaged material
by the healing agent. These characterization methods include different
visualization and spectroscopy techniques and thermal analysis methods. Special
attention is paid to the characterization of the mechanical consequences of self
healing. The effects of self-healing on the mechanical properties such as
stiffness and adhesion of the damaged material are evaluated using the tensile
test, double cantilever beam test, plane strip test, bending test, and adhesion
test (e.g., blister test). Finally, the future direction of the development of
these systems is discussed.
PMID- 29329665
TI - Bioactivation of 1-chloro-2-hydroxy-3-butene, an in vitro metabolite of 1,3
butadiene, by rat liver microsomes.
AB - 1-Chloro-2-hydroxy-3-butene (CHB) is an in vitro metabolite of 1,3-butadiene, a
rodent/human carcinogen. To search for an approach detecting CHB in vivo, it is
vital to obtain a full understanding of CHB metabolism. Previously, we
demonstrated that CHB was bioactivated to 1-chloro-3-buten-2-one (CBO) by alcohol
dehydrogenase. However, CHB metabolism by cytochrome P450s has not been reported.
Thus, in the present study, CHB metabolism by rat liver microsomes was
investigated. The results showed that CHB was converted to 1-chloro-3,4-epoxy-2
butanol (CEB) and CBO. 4-Methylpyrazole, a cytochrome P450 2E1-specific
inhibitor, inhibited the formation of both CEB and CBO, while 1-benzylimidazole,
a generic cytochrome P450 inhibitor, completely abolished the formation of CEB
and CBO, suggesting that CHB metabolism was mediated by cytochrome P450s. Because
the molecules have two chiral centers, CEB was detected as two stereoisomers,
which were designated D-CEB and M-CEB, and were characterized as (2S,3R)-/(2R,3S)
CEB and (2R,3R)-/(2S,3S)-CEB, respectively. The amounts of M-CEB were more than
those of D-CEB by 50-80%. The amounts of CEB and CBO increased linearly over time
from 10 (or 20 min for CBO) to 50 min. CHB metabolism followed Michaelis-Menten
kinetics; the Km and Vmax values were determined to be 6.4 +/- 0.7 mM and 0.10 +/
0.01 nmol/min/mg protein for D-CEB, 4.2 +/- 0.5 mM and 0.16 +/- 0.01 nmol/min/mg
protein for M-CEB, and 4.0 +/- 0.5 mM and 4.6 +/- 0.5 nmol/min/mg protein for
CBO, respectively. Thus, CBO was the dominant product of CHB metabolism.
Moreover, CEB was genotoxic at >= 50 MUM as evaluated by the comet assay.
Collectively, the data showed that CHB could be bioactivated to CEB and CBO by
cytochrome P450s with CBO being the predominant product. Thus, the formation of
CEB and CBO can be used as evidence of CHB production. The products may also play
a role in toxicity of CHB.
PMID- 29329667
TI - Gel-forming mucin interactome drives mucus viscoelasticity.
AB - Mucus is a hydrogel that constitutes the first innate defense in all mammals. The
main organic component of mucus, gel-forming mucins, forms a complex network
through both reversible and irreversible interactions that drive mucus gel
formation. Significant advances in the understanding of irreversible gel-forming
mucins assembly have been made using recombinant protein approaches. However,
little is known about the reversible interactions that may finely modulate mucus
viscoelasticity, which can be characterized using rheology. This approach can be
used to investigate both the nature of gel-forming mucins interactions and
factors that influence hydrogel formation. This knowledge is directly relevant to
the development of new drugs to modulate mucus viscoelasticity and to restore
normal mucus functions in diseases such as in cystic fibrosis. The aim of the
present review is to summarize the current knowledge about the relationship
between the mucus protein matrix and its functions, with emphasis on mucus
viscoelasticity.
PMID- 29329669
TI - Prevalence and Predictors of Symptom Resolution and Functional Restoration in the
Index Knee After Knee Arthroplasty: A Longitudinal Study.
AB - OBJECTIVES: To determine the prevalence of a 1- to 2-year postsurgical pain-free
state and pain plus symptom-free state as well as functional restoration after
knee arthroplasty (KA) and to identify predictors of these outcomes. DESIGN:
Cohort study. SETTING: Communities of 4 sites. PARTICIPANTS: Consecutive
participants (N=383) who underwent KA on at least 1 knee during the first 8 years
of the study (mean age, 67.95+/-8.5y; 61.4% women; n=235). INTERVENTIONS: Not
applicable. MAIN OUTCOME MEASURES: A composite pain score included the Western
Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain scale and 2
generic pain rating scales. Composite pain plus other symptoms scores included 3
pain scales, a stiffness scale, and, in addition, the Knee injury and
Osteoarthritis Outcome Score Symptoms scale. The WOMAC Function scale was used to
quantify functional status. Prevalence estimates and predictors of a pain-free
state, symptom-free state, and a fully functioning state were determined.
RESULTS: A sample of 383 participants with KA was studied, and of these, 34.1%
(95% confidence interval [CI], 29.3%-39.2%; n=131) had a composite score of 0 for
pain. A total of 14.1% (95% CI, 10.8%-18.1%; n=54) had a composite score of 0,
indicating a symptom-free state, whereas 29.0% (95% CI, 24.4%-34.0%; n=111)
achieved a score of 0 on the WOMAC Function scale. CONCLUSIONS: The prevalence of
complete pain relief was 34%, the prevalence of complete pain and symptom relief
was 14%, and the prevalence of complete functional restoration was 29% after KA.
Participants who are older and with lower (better) WOMAC Pain scores were more
likely to be pain-free after surgery. These data collected from a community-based
sample have the potential to inform clinicians screening patients for KA
consultation in a shared decision-making discussion to better align patient
expectations with the most likely outcome.
PMID- 29329670
TI - Motor Skill Interventions in Children With Developmental Coordination Disorder: A
Systematic Review and Meta-Analysis.
AB - OBJECTIVES: To determine the characteristics and effectiveness of motor skill
interventions in children with developmental coordination disorder (DCD) and to
identify potential moderators of training effects using meta-analysis. DATA
SOURCES: A search was conducted in 6 databases (CINAHL Plus, Cochrane Library,
Embase, ERIC, PsycINFO, and PubMed) for articles published between 1995 and
August 2017 using search items which were grouped into 3 components (motor skill
interventions, DCD, and age group of interest). STUDY SELECTION: Studies were
included if they recruited children 3 to 17 years of age with DCD, reported
performance of motor-related skills as outcomes, were published in peer-reviewed
journals, and were written in English. Qualitative synthesis was conducted for
all included studies. Quantitative synthesis (meta-analysis) was only conducted
for studies using a (quasi) randomized controlled trial design. DATA EXTRACTION:
Methodology, participant characteristics, intervention components, outcomes, and
statistically significant training effects of each included study were extracted.
DATA SYNTHESIS: Sixty-six studies met the inclusion criteria with 18 of the
studies eligible for meta-analysis. Motor performance and cognitive, emotional,
and other psychological factors were the most common outcomes. Other 3 outcome
categories included perceptions and/or satisfaction regarding the children's
improvement from significant others, physical fitness, and physical activity and
participation. Immediate and moderate training effects were found for motor
performance (Hedges g=.63; 95% confidence interval [CI], .31-.94; P<.001) and
cognitive, emotional, and other psychological factors (Hedges g=0.65; 95% CI,
0.25-1.04; P=.001). Additionally, dose (minutes in total) and frequency of the
intervention were significant moderators of training effect on motor performance.
CONCLUSIONS: Motor skill interventions are effective in improving motor
competence and performance on cognitive, emotional, and other psychological
aspects in children with DCD in the short term. These effects are more robust in
interventions using a large training dose and a practicing schedule of high
frequency.
PMID- 29329668
TI - Helicobacter pylori induces direct activation of the lymphotoxin beta receptor
and non-canonical nuclear factor-kappa B signaling.
AB - The pathogen Helicobacter pylori, which infects half of the world's population,
is a major risk factor for the development of gastric diseases including chronic
gastritis and gastric cancer. Among H. pylori's virulence factors is the
cytotoxin-associated gene pathogenicity island (cagPAI), which encodes for a type
IV secretion system (T4SS). The T4SS induces fast canonical nuclear factor-kappa
B (NF-kappaB) signaling, a major factor increasing inflammation, supressing
apoptotic cell death and thereby promoting the development of neoplasia. However,
H. pylori's capability to mediate fast non-canonical NF-kappaB signaling is
unresolved, despite a contribution of non-canonical NF-kappaB signaling to
gastric cancer has been suggested. We analyzed signaling elements within non
canonical NF-kappaB in response to H. pylori in epithelial cell lines by
immunoprecipitation, immunoblot, electrophoretic mobility shift assay and RNA
interference knockdown. In addition, tissue samples of H. pylori-infected
patients were investigated by immunohistochemistry. Here, we provide evidence for
a T4SS-dependent direct activation of non-canonical NF-kappaB signaling. We
identified the lymphotoxin beta receptor (LTbetaR) to elicit the fast release of
NF-kappaB inducing kinase (NIK) from the receptor complex leading to non
canonical NF-kappaB signaling. Further, NIK expression was increased in human
biopsies of H. pylori-associated gastritis. Thus, NIK could represent a novel
target to reduce Helicobacter pylori-induced gastric inflammation and pathology.
PMID- 29329671
TI - Localizing two acoustic emission sources simultaneously using beamforming and
singular value decomposition.
AB - Aiming at the issue that the weak AE source is easy to be lost when localizing
simultaneous two acoustic emission (AE) sources by the beamforming method (BFM),
a novel method is developed based on beamforming and singular value decomposition
(SVD). Firstly, the AE data and propagation characteristics of the two
simultaneous AE sources with different frequency, different magnitude and
different positions are obtained, and localization results by directly using the
beamforming are investigated. Then SVD method is introduced to pre-process the
signals from AE sources and solve the problem of missing location. Finally, the
method is verified on a steel plate by AE experiment. The results show that the
localization method based on SVD-beamforming method (SVD-BFM) can effectively
locate the simultaneous double AE sources.
PMID- 29329672
TI - There are probably no differences in arrest of white-spot lesions and plaque
composition between remineralizing and nonfluoridated toothpastes.
PMID- 29329673
TI - Use of naproxen before in-office tooth bleaching may result in a small decrease
in tooth sensitivity during and immediately after the procedure.
PMID- 29329674
TI - Long-term esthetic outcomes of patients with cleft lip and palate have improved
over time.
PMID- 29329675
TI - Root canal retreatment with Thermafil as an obturator seems to have acceptable
survival after 5 years.
PMID- 29329676
TI - A mixed linear model controlling for case underascertainment across multiple
cancer registries estimated time trends in survival.
AB - OBJECTIVES: Large temporal and geographical variation in survival rates estimated
from epidemiological cancer registries coupled with heterogeneity in death
certificate only (DCO) notifications makes it difficult to interpret trends in
survival. The aim of our study is to introduce a method for estimating such
trends while accounting for heterogeneity in DCO notifications in a cancer site
specific manner. STUDY DESIGN AND SETTING: We used the data of 4.0 million cancer
cases notified in 14 German epidemiological cancer registries. Annual 5-year
relative survival rates from 2002 through 2013 were estimated, and proportions of
DCO notifications were recorded. "DCO-excluded" survival rates were regressed on
DCO proportions and calendar years using a mixed linear model with cancer
registry as a random effect. Based on this model, trends in survival rates were
estimated for Germany at 0% DCO. RESULTS: For most cancer sites and age groups,
we estimated significant positive trends in survival. Age-standardized survival
for all cancers combined increased by 7.1% units for women and 10.8% units for
men. CONCLUSION: The described method could be used to estimate trends in cancer
survival based on the data from epidemiological cancer registries with differing
DCO proportions and with changing DCO proportions over time.
PMID- 29329677
TI - Living systematic reviews, not only for clinical (placebo) research.
PMID- 29329678
TI - Apelin-13 ameliorates cognitive impairments in 6-hydroxydopamine-induced
substantia nigra lesion in rats.
AB - Although Parkinson's disease (PD) is well known with its motor deficits, the
patients often suffer from cognitive dysfunction. Apelin, as the endogenous
ligand of the APJ receptor, is found in several brain regions such as substantia
nigra and mesolimbic pathway. However, the role of apelin in cognition and
cognitive disorders has not been fully clarified. In this study the effects of
apelin-13 were investigated on cognitive disorders in rat Parkinsonism
experimental model. 6-hydroxydopamine (6-OHDA) was administrated into the
substantia nigra. Apelin-13 (1, 2 and 3MUg/rat) was administered into the
substantia nigra one week after the 6-OHDA injection. Morris water maze (MWM),
object location and novel object recognition tests were performed one month after
the apelin injection. 6-OHDA-treated animals showed a significant impairment in
cognitive functions which was revealed by the increased in the escape latency and
traveled distance in MWM test and decreased in the exploration index in novel
object recognition and object location tasks. Apelin-13 (3MUg/rat) significantly
attenuates the mentioned cognitive impairments in 6-OHDA-treated animals. In
conclusion, the data support the pro-cognitive property of apelin-13 in 6-OHDA
induced cognitive deficit and provided a new pharmacological aspect of the
neuropeptide apelin.
PMID- 29329679
TI - Standardization of a fast and effective method for the generation and detection
of platelet-derived microparticles by a flow cytometer.
AB - The Flow Cytometry is the principal method used to measure platelet-derived
microparticles (PDMPs), by fluorescent properties analysis. PDMPs (0.1-1.0 MUm)
are abundant in circulation, accounting for approximately 90% of the
microparticles and are associated with Cardiovascular Disease, the leading cause
of death in the world.
PMID- 29329680
TI - Correlation of severity of chronic obstructive pulmonary disease with potential
biomarkers.
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a non-specific
inflammation, which involves the airways, lung parenchyma and pulmonary vessels.
The inflammation causes the activation of inflammatory cells and the release of
various inflammatory mediators such as interleukin-1 beta, interleukin-6 and
tumor necrosis factor alpha (TNF-a). The present study was designed to assess the
serum cytokines [Interleukin-1beta (IL-1beta), Interleukin-6 (IL-6), Tumor
necrosis factor-alpha (TNF-alpha)] levels in chronic obstructive pulmonary
disease (COPD) patients and they were correlated with severity of disease by
spirometric measurements. MATERIALS AND METHODS: A total of 384 COPD patients and
50 healthy controls were enrolled in this study. The COPD patients were divided
according to gold stages ie: mild, moderate, severe and very severe. 5 ml of
venous blood samples were taken from all participants and it was collected in a
test tube containing anticoagulant and then centrifuged at 3000 rpm for 10 min.
Serum was separated and used to measure the amount of TNF-alpha, il-1beta, and IL
6. Spirometry was performed according to the criteria set by the Gold 2012
RESULTS: Tnf-alpha (pg/ml), IL-6 (pg/ml), IL-1beta (pg/ml) serum levels in COPD
patients and healthy controls subjects were measured. Tnf-alpha and IL-6 serum
levels were significantly (<0.001) higher in COPD patients compared to healthy
control subjects. Likewise, IL-1 beta levels were also significantly (p-value =
0.022) higher in COPD patients compared to healthy control subjects. The
distribution of Tnf-alpha, IL-6, IL-1beta (pg/ml) serum levels in COPD patients
in relation to GOLD grading. There was a significant (p < 0.001) difference in
the level of TNF-alpha, IL-6 and IL-1beta (pg/ml) among the severity of COPD. The
posthoc analysis revealed that the TNF-alpha was significantly (p < 0.05) higher
among the than mild, moderate, severe and very severe COPD patients. A similar
observation was also found for IL-6. However, IL-6 was significantly (p < 0.05)
higher among mild, moderate, severe and very severe COPD patients. There was
significant (p = < 0.0001) difference in the level of IL-1beta in the different
severity of COPD. The posthoc comparison test showed that IL-1beta levels were
significantly (p < 0.05) higher among the mild, moderate, severe and very severe
COPD patients. CONCLUSION: The present study signifies that the levels of TNF
alpha, IL-1beta, and IL-6 are directly proportional to the post-bronchodilator
FEV1 percentage. Results provide population-based evidence that COPD is
independently associated with low-grade systemic inflammation, with a different
inflammatory pattern than that observed in healthy subjects. Overall, these
results identify a novel systemic inflammatory COPD phenotype that may be the
target of specific research and treatment.
PMID- 29329681
TI - Expanding the genetic profile of Hay-Wells syndrome.
PMID- 29329682
TI - Feline coronavirus: Insights into viral pathogenesis based on the spike protein
structure and function.
AB - Feline coronavirus (FCoV) is an etiological agent that causes a benign enteric
illness and the fatal systemic disease feline infectious peritonitis (FIP). The
FCoV spike (S) protein is considered the viral regulator for binding and entry to
the cell. This protein is also involved in FCoV tropism and virulence, as well as
in the switch from enteric disease to FIP. This regulation is carried out by
spike's major functions: receptor binding and virus-cell membrane fusion. In this
review, we address important aspects in FCoV genetics, replication and
pathogenesis, focusing on the role of S. To better understand this, FCoV S
protein models were constructed, based on the human coronavirus NL63 (HCoV-NL63)
S structure. We describe the specific structural characteristics of the FCoV S,
in comparison with other coronavirus spikes. We also revise the biochemical
events needed for FCoV S activation and its relation to the structural features
of the protein.
PMID- 29329683
TI - Respiratory disease in ball pythons (Python regius) experimentally infected with
ball python nidovirus.
AB - Circumstantial evidence has linked a new group of nidoviruses with respiratory
disease in pythons, lizards, and cattle. We conducted experimental infections in
ball pythons (Python regius) to test the hypothesis that ball python nidovirus
(BPNV) infection results in respiratory disease. Three ball pythons were
inoculated orally and intratracheally with cell culture isolated BPNV and two
were sham inoculated. Antemortem choanal, oroesophageal, and cloacal swabs and
postmortem tissues of infected snakes were positive for viral RNA, protein, and
infectious virus by qRT-PCR, immunohistochemistry, western blot and virus
isolation. Clinical signs included oral mucosal reddening, abundant mucus
secretions, open-mouthed breathing, and anorexia. Histologic lesions included
chronic-active mucinous rhinitis, stomatitis, tracheitis, esophagitis and
proliferative interstitial pneumonia. Control snakes remained negative and free
of clinical signs throughout the experiment. Our findings establish a causal
relationship between nidovirus infection and respiratory disease in ball pythons
and shed light on disease progression and transmission.
PMID- 29329685
TI - Association of provider recommendation and offer and influenza vaccination among
adults aged >=18 years - United States.
AB - BACKGROUND: Influenza vaccination has been recommended for all persons aged >=6
months since 2010. METHODS: Data from the 2016 National Internet Flu Survey were
analyzed to assess provider vaccination recommendations and early influenza
vaccination during the 2016-17 season among adults aged >=18 years. Predictive
marginals from a multivariable logistic regression model were used to identify
factors independently associated with early vaccine uptake by provider
vaccination recommendation status. RESULTS: Overall, 24.0% visited a provider who
both recommended and offered influenza vaccination, 9.0% visited a provider who
only recommended but did not offer, 25.1% visited a provider who neither
recommended nor offered, and 41.9% did not visit a doctor from July 1 through
date of interview. Adults who reported that a provider both recommended and
offered vaccine had significantly higher vaccination coverage (66.6%) compared
with those who reported that a provider only recommended but did not offer
(48.4%), those who neither received recommendation nor offer (32.0%), and those
who did not visit a doctor during the vaccination period (28.8%). Results of
multivariable logistic regression indicated that having received a provider
recommendation, with or without an offer for vaccination, was significantly
associated with higher vaccination coverage after controlling for demographic and
access-to-care factors. CONCLUSIONS: Provider recommendation was significantly
associated with influenza vaccination. However, overall, 67.0% of adults did not
visit a doctor during the vaccination period or did visit a doctor but did not
receive a provider recommendation. Evidence-based strategies such as client
reminder/recall, standing orders, provider reminders, or health systems
interventions in combination should be undertaken to improve provider
recommendation and influenza vaccination coverage. Other factors significantly
associated with a higher level of influenza vaccination included age >=50 years,
being Hispanic, having a college or higher education, having a usual place for
medical care, and having public health insurance.
PMID- 29329684
TI - Impact of seasonal influenza vaccination in the presence of vaccine interference.
AB - BACKGROUND: Annual influenza vaccination is a key to preventing widespread
influenza infections. Recent reports of influenza vaccine effectiveness (VE)
indicate that vaccination in prior years may reduce VE in the current season,
suggesting vaccine interference. The purpose of this study is to evaluate the
potential effect of repeat influenza vaccinations in the presence of vaccine
interference. METHODS: Using literature-based parameters, an age-structured
influenza equation-based transmission model was used to determine the optimal
vaccination strategy, while considering the effect of varying levels of
interference. RESULTS: The model shows that, even in the presence of vaccine
interference, revaccination reduces the influenza attack rate and provides
individual benefits. Specifically, annual vaccination is a favored strategy over
vaccination in alternate years, as long as the level of residual protection is
less than 58% or vaccine interference effect is minimal. Furthermore, the
negative impact of vaccine interference may be offset by increased vaccine
coverage levels. CONCLUSIONS: Even in the presence of potential vaccine
interference, our work provides a population-level perspective on the potential
merits of repeated influenza vaccination. This is because repeat vaccination
groups had lower attack rates than groups that omitted the second vaccination
unless vaccine interference was at very high, perhaps implausible, levels.
PMID- 29329686
TI - Highlighting priority areas for bovine viral diarrhea control in Italy: A
phylogeographic approach.
AB - The prevalence and genetic diversity of bovine viral diarrhea virus (BVDV) in a
geographic area are largely influenced by live animal trade and management
practices. Despite control and eradication programs currently underway in several
European countries, the risk of BVDV spread within and among countries is still
present. BVDV-1 is the predominant type circulating in European cattle
population. In this study, a phylogeographic analysis was applied to the BVDV-1
highest prevalent subtypes in Italy to reconstruct the origin and spatial
temporal distribution and to trace main viral flows between different locations
to highlight priority areas for BVDV control. A comprehensive dataset of BVDV-1b
(n = 173) and 1e (n = 172) 5' UTR sequences was analysed, including both novel
and published sequences from Italy and from European countries bordering and/or
with commercial cattle flows with Italy. A common phylogeographic pattern was
observed for BVDV-1b and 1e subtypes: interspersion from multiple Italian areas
and European countries was widespread until the end of the last century, whereas
significant local clusters were observed starting from 2000. These findings
support a continuous viral flow among different areas over long time scales with
no evidence of significant geographical structure, while local transmission
networks are limited to more recent years. Northern Italy has been confirmed as
the area of origin of the main clades of both BVDV subtypes at national level,
acting both as a crucial area for introduction and a maintenance source for other
areas. Piedmont, Central and Southern Italian regions contributed to limited
geographical distribution and local BVDV-1b and 1e persistence. On the whole,
priority control measures for BVDV-1b and 1e in Italy should be focused on: i)
implementation of BVDV systematic control in all Northern Italian regions to
break the viral flow from larger to smaller animal populations; and ii) breaking
the dynamics of infections in regions with self-maintenance of BVDV by voluntary
control programs.
PMID- 29329688
TI - Motorizing and Optimizing Ultrasound Strain Elastography for Detection of
Intrauterine Growth Restriction Pregnancies.
AB - Intrauterine growth restriction is a prevalent disease in pregnancy in which
placental insufficiency leads to 5 to 10 times higher mortality and lifelong
morbidities. The current detection rate is poor, and recently, ultrasound strain
elastography (USEL) was proposed as a new diagnostic technique. Currently,
placental USEL uses maternal subcutaneous fat as the reference layer, but this is
not ideal as fat tissue stiffness can vary widely between subjects. Current USEL
also uses manual palpation, and under different compression depths and rates,
viscoelastic tissues such as placenta can yield different stiffness results. In
the study described here, we strove to improve placental USEL by (i) using an
external polymeric pad of known stiffness as the reference layer and (ii)
adopting motorized control of the transducer during USEL to standardize palpation
motion. Results indicated that motorized USEL reduced measurement variability by
67% compared with freehand USEL. Satisfactory and statistically significant
correlations between USEL measurements and mechanical testing validation results
were obtained for our new USEL protocol. Placental tissues were found to be non
linear and viscoelastic in nature and, thus, differed in stiffness at different
compression rates and depths. Our study also revealed that there was a specific
compression depth and rate during USEL that provided better correlation to
mechanical testing, and should be considered in clinical placental USEL.
PMID- 29329690
TI - Author's Response.
PMID- 29329689
TI - Pediatric obesity: Current concepts.
AB - This discussion reflects on concepts of obesity in children and adolescents in
the early 21st century. It includes reflections on its history, definition,
epidemiology, diagnostic perspectives, psychosocial considerations,
musculoskeletal complications, endocrine complications and principles of
management. In addition to emphasis on diet and exercise, research and clinical
applications in the second decade of the 21st century emphasize the increasing
use of pharmacotherapy and bariatric surgery for adolescent and adult populations
with critical problems of overweight and obesity. We conclude with a discussion
of future directions in pediatric obesity management.
PMID- 29329691
TI - Communication Disparity Between the Bereaved and Others: What Hurts Them and What
Is Unhelpful? A Nationwide Study of the Cancer Bereaved.
AB - CONTEXT: The importance of communication between the cancer bereaved and others
has been emphasized, but little is known about the more problematic aspects of
this communication such as "unhelpful communication." OBJECTIVES: The aim of this
study was to establish which types of communication are perceived by the bereaved
to be unhelpful. METHODS: We conducted a cross-sectional, anonymous, nationwide
survey at 103 certified hospice facilities/palliative care units in Japan.
RESULTS: A total of 630 (63%) bereaved responded. Over 60% of the bereaved
experiencing such communication considered it to be unhelpful, with the most
unhelpful communication being "They emphasized the positive aspects of death."
Thirteen items related to communication were separated into two factors ("advice
for recovery" and "comments on cancer") by factor analysis. "Comments on cancer"
were more unhelpful to them and were more often provided by those around them.
With regard to "advice for recovery," losing a spouse was a stronger predictor
with a higher odds ratio for communication distress than losing a parent (odds
ratio, 5.34; 95% CI, 1.63-17.57). CONCLUSION: A number of the bereaved have
experienced unhelpful communication regarding advice on dealing with bereavement
and cancer. To prevent putting an unnecessary burden on the bereaved with such
unhelpful communication, it is essential to understand problematic aspects. Even
when people have no intention of hurting the bereaved, some communication may do
so. Communication with the bereaved is also a core clinical skill required by
health professionals, and further efforts are required to support the grieving
process.
PMID- 29329692
TI - Potential psychological & neural mechanisms in binge eating disorder:
Implications for treatment.
AB - Binge Eating Disorder (BED) is a newly-established eating disorder diagnosis in
the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM
5). Although systematic research on BED is in its infancy and many studies
feature small samples, several observations emerge. First, we review diagnostic,
developmental, and socio-demographic features of BED. Next, although BED and
obesity are linked and frequently co-occur, we review data suggesting that BED is
a distinct phenotype. Importantly, we take a mechanism-focused approach and
propose four psychological processes with neurobiological bases that may uniquely
differentiate BED from obesity: emotion reactivity, food-cue reactivity, food
craving, and cognitive control. Further, we propose that interactions between
impairments in cognitive control and increased emotional reactivity, food-cue
reactivity, and craving may underlie emotion dysregulation and promote binge
eating. Consistently, neuroimaging studies point towards neural alterations in
the response to rewards and to food specifically, and suggest preliminary links
between impaired cognitive-control-related neural activity and binge eating.
However, additional systematic work is required in this area. We conclude with a
detailed review of treatment approaches to BED; specifically, we suggest that
psychological and pharmacological treatments that target core mechanisms -
including cognitive control and emotion/craving dysregulation - may be
particularly effective.
PMID- 29329693
TI - BOLD fMRI signal in stroke patients and its importance for prognosis in the
subacute disease period - Preliminary report.
AB - : Functional magnetic resonance imaging (fMRI) allows for the assessment of
neuronal activity through the blood-level-dependent signal. The purpose of study
was to evaluate the pattern of brain activity in fMRI in patients with ischemic
stroke and to assess the potential relationship between the activity pattern and
the neurological/functional status. METHODS: The fMRI was performed in patients
up to 4th day of stroke. All the patients were analyzed according to NIHSS on 1st
day and mRankin scale on 14th day of stroke, followed by analyzing of fMRI
signal. RESULTS: The study enrolled 13 patients at a mean age of 64.3years. Eight
(61.5%) showed cerebellar activation and 2 (15.38%)- insular activation. In those
who scored 0-2 on mRankin scale, the most frequently observed activity was
located in the regions: the M1, SMA and PMC in the stroke hemisphere and the
cerebellum. In those cases, the non-stroke hemisphere was more frequently
involved in the areas: the M1 and PMC. There was a tendency for a better
prognosis in relation to age <65years and activation of the SMA in the stroke
hemisphere. CONCLUSION: There are differences observed in the activation areas of
the cerebral cortex both in the stroke and non-stroke hemispheres. More than half
of the patients with hemispheric stroke but all with good outcome showed
cerebellar activation. There is probable positive correlation between the BOLD
signal size, young age, activation of supplementary motor area in stroke
hemisphere and good functional status of patients in the subacute period of
stroke.
PMID- 29329687
TI - Bubble-Induced Color Doppler Feedback Correlates with Histotripsy-Induced
Destruction of Structural Components in Liver Tissue.
AB - Bubble-induced color Doppler (BCD) is a histotripsy-therapy monitoring technique
that uses Doppler ultrasound to track the motion of residual cavitation nuclei
that persist after the collapse of the histotripsy bubble cloud. In this study,
BCD is used to monitor tissue fractionation during histotripsy tissue therapy,
and the BCD signal is correlated with the destruction of structural and non
structural components identified histologically to further understand how BCD
monitors the extent of treatment. A 500-kHz, 112-element phased histotripsy array
is used to generate approximately 6- * 6- * 7-mm lesions within ex vivo bovine
liver tissue by scanning more than 219 locations with 30-1000 pulses per
location. A 128-element L7-4 imaging probe is used to acquire BCD signals during
all treatments. The BCD signal is then quantitatively analyzed using the time-to
peak rebound velocity (tprv) metric. Using the Pearson correlation coefficient,
the tprv is compared with histologic analytics of lesions generated by various
numbers of pulses using a significance level of 0.001. Histologic analytics in
this study include viable cell count, reticulin-stained type III collagen area
and trichrome-stained type I collagen area. It is found that the tprv metric has
a statistically significant correlation with the change in reticulin-stained type
III collagen area with a Pearson correlation coefficient of -0.94 (p <0.001),
indicating that changes in BCD are more likely because of destruction of the
structural components of tissue.
PMID- 29329694
TI - Management of Refractory Vasodilatory Shock.
AB - Refractory shock is a lethal manifestation of cardiovascular failure defined by
an inadequate hemodynamic response to high doses of vasopressor medications.
Approximately 7% of critically ill patients will develop refractory shock, with
short-term mortality exceeding 50%. Refractory vasodilatory shock develops from
uncontrolled vasodilation and vascular hyporesponsiveness to endogenous
vasoconstrictors, causing failure of physiologic vasoregulatory mechanisms.
Standard approaches to the initial management of shock include fluid
resuscitation and initiation of norepinephrine. When these measures are
inadequate to restore BP, vasopressin or epinephrine can be added. Few randomized
studies exist to guide clinical management and hemodynamic stabilization in
patients who do not respond to this standard approach. Adjunctive therapies, such
as hydrocortisone, thiamine, and ascorbic acid, may increase BP in severe shock
and should be considered when combination vasopressor therapy is needed. Novel
vasopressor agents, such as synthetic human angiotensin II, can increase BP and
reduce the need for high doses of catecholamine vasopressors in severe or
refractory vasodilatory shock. Few effective rescue therapies exist for
established refractory shock, which emphasizes the importance of aggressive
intervention before refractory shock develops, including the earlier initiation
of rational combination vasopressor therapy. The present review discusses the
diagnosis and management of refractory shock to offer guidance for management of
this important clinical problem and to provide a framework for future research.
PMID- 29329695
TI - A patient with pembrolizumab-induced fatal polymyositis.
PMID- 29329696
TI - Pharmacokinetics partly explains the relationship between carcinoembryonic
antigen level and survival of colorectal cancer patients treated with
ramucirumab.
PMID- 29329698
TI - Effect of combined exercise training on serum brain-derived neurotrophic factor,
suppressors of cytokine signaling 1 and 3 in patients with multiple sclerosis.
AB - BACKGROUND: Suppressors of cytokine signaling (SOCS) and brain-derived
neurotrophic factor (BDNF) are important immunologic, and neurotrophic factors
for MS pathogenesis. The impact of exercise on these factors is yet to be fully
elucidated in patients with MS. OBJECTIVE: The primary aim of this study is to
investigate the effect of 8-week combined exercise training on serum
concentrations of SOCS1, SOCS3, and BDNF. The secondary aim is to determine the
effects of combined exercise training on balance, functional exercise capacity,
and fatigue in patients with MS. METHODS: Serum SOCS1, SOCS3, and BDNF levels
were assessed in 36 MS patients and 18 healthy individuals. In addition, balance,
functional exercise capacity, and fatigue were assessed in the patients with MS.
The patients were randomly divided into the combined exercise group (MS-EX, n:18)
and the control group (MS-C, n:18). MS-EX received an 8-week combined exercise
training. RESULTS: The serum SOCS1, SOCS3, and BDNF levels were similar in the MS
patients and healthy control (HC). In MS-EX, the serum BDNF level, balance,
functional exercise capacity, and fatigue improved after 8weeks (p<0.05), but the
serum SOCS1, and SOCS3 levels did not change significantly (p>0.05). In MS-C, the
serum SOCS1 level, and fatigue increased significantly after 8weeks (p<0.05), but
serum SOCS3, BDNF, balance and functional exercise capacity did not change
(p>0.05). CONCLUSIONS: In summary, the combined exercise training improved BDNF,
and physical performance in patients with MS. But, future studies are needed to
clarify the role of SOCS proteins in MS pathogenesis and the effect of exercise
on SOCS.
PMID- 29329697
TI - Ageing perceptions and non-adherence to aromatase inhibitors among breast cancer
survivors.
AB - PURPOSE: Aromatase inhibitors (AIs) are a potentially life-saving treatment for
breast cancer survivors, yet poor adherence to treatment is a prevalent problem.
A common adverse effect of AI treatment is arthralgia, which is identified by
survivors as a major reason for treatment discontinuation. Women who experience
arthralgia on AIs often report feeling they have aged rapidly while on the
treatment. In the present study, we examined whether arthralgia-associated ageing
perceptions predicted non-adherence. PATIENTS AND METHODS: We conducted a
prospective cohort study among women with stage I-III breast cancer, who were on
an AI and completed the Penn Arthralgia Aging Scale within 2 years of AI
initiation. Adherence data were abstracted from medical charts by trained raters.
Cox proportional hazard analysis was used to determine the relationship between
ageing perceptions and time to non-adherence. All analyses included adjustments
for joint pain severity. RESULTS: Among 509 participants, 144 (28.3%) were non
adherent. As hypothesised, women with high levels of ageing perceptions were at
greater risk of non-adherence than women with low levels of ageing perceptions
(adjusted hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.10-2.67; p =
.02). High levels of depressive symptoms were also uniquely associated with
increased risk of non-adherence (adjusted HR, 1.63; 95% CI, 1.03-2.59; p = .04).
CONCLUSION: Perceptions of ageing related to arthralgia and depressive symptoms
predicted non-adherence to AIs. These findings suggest that interventions that
address negative beliefs about ageing due to AI-related arthralgia and depressive
mood can potentially improve rates of adherence to AIs.
PMID- 29329699
TI - Soluble CD40 ligand disrupts the blood-brain barrier and exacerbates inflammation
in experimental autoimmune encephalomyelitis.
AB - Serum soluble CD40 ligand (sCD40L) has been reported to positively correlate with
the albumin quotient, a marker of blood-brain barrier (BBB) breakdown, in
patients with multiple sclerosis (MS). To clarify the mechanisms of sCD40L in MS
pathophysiology, sCD40L was administered to experimental autoimmune
encephalomyelitis (EAE) mice and a human brain microvascular endothelial cell
(HBMEC)-based BBB model. The high-dose sCD40L group showed a worse EAE score than
the low-dose and control groups. BBB permeability was increased by administering
sCD40L in a HBMEC-based BBB model. Thus, sCD40L induces more severe inflammation
in the central nervous system by disrupting the BBB.
PMID- 29329700
TI - [A Listeria breast abscess in a man].
AB - INTRODUCTION: Listeriosis is a food-borne illness leading to bacteriemia or
central nervous system infection especially in pregnant women or high-risk
patients. It is rarely a localized infection. Breast contamination has rarely
been reported in lactating women. We report a breast abscess in man. CASE REPORT:
A 80 year old man, hypertensive and arrhythmic, was explored for weakness and
dehydration. Type 2 diabetes and chronic lymphocytic leukemia were diagnosed.
Clinical examination disclosed a breast abcess related to L monocytogenes
infection. Histopathological study also revealed a breast subcutaneous
infiltration by chronic lymphocytic leukemia. CONCLUSION: Listeriosis sometimes
uncover an unknown immunosuppression, especially in the elderly. Breast is a non
sterile tissue containing a stable microbiome partly from digestive origin. It
can thereby be contaminated by Listeria. The specific cutaneous infiltrate of
chronic lymphocytic leukemia can create the conditions for a local infection.
PMID- 29329701
TI - Automatic information extraction from unstructured mammography reports using
distributed semantics.
AB - To date, the methods developed for automated extraction of information from
radiology reports are mainly rule-based or dictionary-based, and, therefore,
require substantial manual effort to build these systems. Recent efforts to
develop automated systems for entity detection have been undertaken, but little
work has been done to automatically extract relations and their associated named
entities in narrative radiology reports that have comparable accuracy to rule
based methods. Our goal is to extract relations in a unsupervised way from
radiology reports without specifying prior domain knowledge. We propose a hybrid
approach for information extraction that combines dependency-based parse tree
with distributed semantics for generating structured information frames about
particular findings/abnormalities from the free-text mammography reports. The
proposed IE system obtains a F1-score of 0.94 in terms of completeness of the
content in the information frames, which outperforms a state-of-the-art rule
based system in this domain by a significant margin. The proposed system can be
leveraged in a variety of applications, such as decision support and information
retrieval, and may also easily scale to other radiology domains, since there is
no need to tune the system with hand-crafted information extraction rules.
PMID- 29329702
TI - Ten factors to consider when developing usability scenarios and tasks for health
information technology.
AB - The quality of usability testing is highly dependent upon the associated
usability scenarios. To promote usability testing as part of electronic health
record (EHR) certification, the Office of the National Coordinator (ONC) for
Health Information Technology requires that vendors test specific capabilities of
EHRs with clinical end-users and report their usability testing process -
including the test scenarios used - along with the results. The ONC outlines
basic expectations for usability testing, but there is little guidance in
usability texts or scientific literature on how to develop usability scenarios
for healthcare applications. The objective of this article is to outline key
factors to consider when developing usability scenarios and tasks to evaluate
computer-interface based health information technologies. To achieve this goal,
we draw upon a decade of our experience conducting usability tests with a variety
of healthcare applications and a wide range of end-users, to include healthcare
professionals as well as patients. We discuss 10 key factors that influence
scenario development: objectives of usability testing; roles of end-user(s);
target performance goals; evaluation time constraints; clinical focus; fidelity;
scenario-related bias and confounders; embedded probes; minimize risks to end
users; and healthcare related outcome measures. For each factor, we present an
illustrative example. This article is intended to aid usability researchers and
practitioners in their efforts to advance health information technologies. The
article provides broad guidance on usability scenario development and can be
applied to a wide range of clinical information systems and applications.
PMID- 29329703
TI - Highly-sensitive microRNA detection based on bio-bar-code assay and catalytic
hairpin assembly two-stage amplification.
AB - Herein, a highly-sensitive microRNA (miRNA) detection strategy was developed by
combining bio-bar-code assay (BBA) with catalytic hairpin assembly (CHA). In the
proposed system, two nanoprobes of magnetic nanoparticles functionalized with DNA
probes (MNPs-DNA) and gold nanoparticles with numerous barcode DNA (AuNPs-DNA)
were designed. In the presence of target miRNA, the MNP-DNA and AuNP-DNA
hybridized with target miRNA to form a "sandwich" structure. After "sandwich"
structures were separated from the solution by the magnetic field and
dehybridized by high temperature, the barcode DNA sequences were released by
dissolving AuNPs. The released barcode DNA sequences triggered the toehold strand
displacement assembly of two hairpin probes, leading to recycle of barcode DNA
sequences and producing numerous fluorescent CHA products for miRNA detection.
Under the optimal experimental conditions, the proposed two-stage amplification
system could sensitively detect target miRNA ranging from 10 pM to 10 aM with a
limit of detection (LOD) down to 97.9 zM. It displayed good capability to
discriminate single base and three bases mismatch due to the unique sandwich
structure. Notably, it presented good feasibility for selective multiplexed
detection of various combinations of synthetic miRNA sequences and miRNAs
extracted from different cell lysates, which were in agreement with the
traditional polymerase chain reaction analysis. The two-stage amplification
strategy may be significant implication in the biological detection and clinical
diagnosis.
PMID- 29329704
TI - A detailed electrochemical impedance spectroscopy study of a bismuth-film glassy
carbon electrode for trace metal analysis.
AB - A systematic electrochemical impedance spectroscopy (EIS) analysis at different
potentials of an in situ-prepared bismuth-film glassy carbon electrode (BiFE) in
0.1 M acetate buffer solution is reported. This electrode is employed in the
square-wave anodic stripping voltammetry (SWASV) technique for the determination
of trace amounts of the heavy metals Zn, Cd, and Pb. The method was first
validated for detection limit, linear range, sensitivity, precision and accuracy
to clearly prove the superior action of BiFE compared with the bare glassy carbon
electrode (GCE). Next, in order to investigate the characteristics of this
sensor, EIS measurements were carried out at slightly more negative potentials
than the potentials at which each individual stripping signal is detected, after
the deposition step at different deposition potentials. For comparison, EIS
measurements were also performed at open circuit potential. The studied trace
metal concentration range (5-20 ppb) did not significantly influence the
capacitive and resistive behaviour of the BiFE which explains why the performance
of this sensor is superior compared with the bare GCE. The higher sensitivity of
the SWASV method for BiFE compared with the bare GCE was explained by the lower
polarisation resistance values of the former. Moreover, the potential of zero
charge was also determined, and an explanation whether the system is under
kinetic- and/or diffusion-controlled process is given.
PMID- 29329706
TI - Unattended reaction monitoring using an automated microfluidic sampler and on
line liquid chromatography.
AB - In-process sampling and analysis is an important aspect of monitoring kinetic
profiles and impurity formation or rejection, both in development and during
commercial manufacturing. In pharmaceutical process development, the technology
of choice for a substantial portion of this analysis is high-performance liquid
chromatography (HPLC). Traditionally, the sample extraction and preparation for
reaction characterization have been performed manually. This can be time
consuming, laborious, and impractical for long processes. Depending on the
complexity of the sample preparation, there can be variability introduced by
different analysts, and in some cases, the integrity of the sample can be
compromised during handling. While there are commercial instruments available for
on-line monitoring with HPLC, they lack capabilities in many key areas. Some do
not provide integration of the sampling and analysis, while others afford limited
flexibility in sample preparation. The current offerings provide a limited number
of unit operations available for sample processing and no option for workflow
customizability. This work describes development of a microfluidic automated
program (MAP) which fully automates the sample extraction, manipulation, and on
line LC analysis. The flexible system is controlled using an intuitive Microsoft
Excel based user interface. The autonomous system is capable of unattended
reaction monitoring that allows flexible unit operations and workflow
customization to enable complex operations and on-line sample preparation. The
automated system is shown to offer advantages over manual approaches in key areas
while providing consistent and reproducible in-process data.
PMID- 29329705
TI - Low-cost and disposable sensors for the simultaneous determination of coenzyme
Q10 and alpha-lipoic acid using manganese (IV) oxide-modified screen-printed
graphene electrodes.
AB - In this work, for the first time, manganese (IV) oxide-modified screen-printed
graphene electrodes (MnO2/SPGEs) were developed for the simultaneous
electrochemical detection of coenzyme Q10 (CoQ10) and alpha-lipoic acid (ALA).
This sensor exhibits attractive benefits such as simplicity, low production
costs, and disposability. Cyclic voltammetry (CV) was used to characterize the
electrochemical behavior of the analyte and investigate the capacitance and
electroactive surface area of the unmodified and modified electrode surfaces. The
electrochemical behavior of CoQ10 and ALA on MnO2/SPGEs was also discussed.
Additionally, square wave anodic stripping voltammetry (SWASV) was used for the
quantitative determination of CoQ10 and ALA. Under optimal conditions, the
obtained signals are linear in the concentration range from 2.0 to 75.0 MUg mL-1
for CoQ10 and 0.3-25.0 MUg mL-1 for ALA. The low limits of detection (LODs) were
found to be 0.56 MUg mL-1 and 0.088 MUg mL-1 for CoQ10 and ALA, respectively.
Moreover, we demonstrated the utility and applicability of the MnO2/SPGE sensor
through simultaneous measurements of CoQ10 and ALA in dietary supplements. The
sensor provides high accuracy measurements, exhibiting its high potential for
practical applications.
PMID- 29329707
TI - Simultaneous determination of 117 pesticides and 30 mycotoxins in raw coffee,
without clean-up, by LC-ESI-MS/MS analysis.
AB - This paper describes the optimization and validation of an acetonitrile based
method for simultaneous extraction of multiple pesticides and mycotoxins from raw
coffee beans followed by LC-ESI-MS/MS determination. Before extraction, the raw
coffee samples were milled and then slurried with water. The slurried samples
were spiked with two separate standard solutions, one containing 131 pesticides
and a second with 35 mycotoxins, which were divided into 3 groups of different
relative concentration levels. Optimization of the QuEChERS approach included
performance tests with acetonitrile acidified with acetic acid or formic acid,
with or without buffer and with or without clean-up of the extracts before LC-ESI
MS/MS analysis. For the clean-up step, seven d-SPE sorbents and their various
mixtures were evaluated. After method optimization a complete validation study
was carried out to ensure adequate performance of the extraction and
chromatographic methods. The samples were spiked at 3 concentrations levels with
both mycotoxins and pesticides (with 6 replicates at each level, n = 6) and then
submitted to the extraction procedure. Before LC-ESI-MS/MS analysis, the
acetonitrile extracts were diluted 2-fold with methanol, in order to improve the
chromatographic performance of the early-eluting polar analytes. Calibration
standard solutions were prepared in organic solvent and in blank coffee extract
at 7 concentration levels and analyzed 6 times each. The method was assessed for
accuracy (recovery %), precision (RSD%), selectivity, linearity (r2), limit of
quantification (LOQ) and matrix effects (%).
PMID- 29329709
TI - Characterization of singly and multiply PEGylated insulin isomers by reversed
phase ultra-performance liquid chromatography interfaced with ion mobility mass
spectrometry.
AB - Conjugation of poly(ethylene glycol) (PEG) to protein drugs (PEGylation) is
increasingly utilized in the biotherapeutics field because it improves
significantly the drugs' circulatory half-life, solubility, and shelf-life. The
activity of a PEGylated drug depends on the number, size, and location of the
attached PEG chain(s). This study introduces a 2D separation approach, including
reversed-phase ultra-performance liquid chromatography (RP-UPLC) and ion mobility
mass spectrometry (IM-MS), in order to determine the structural properties of the
conjugates, as demonstrated for a PEGylated insulin sample that was prepared by
random amine PEGylation. The UPLC dimension allowed separation based on polarity.
Electrospray ionization (ESI) of the eluates followed by in-source dissociation
(ISD) truncated the PEG chains and created insulin fragments that provided site
specific information based on whether they contained a marker at the potential
conjugation sites. Separation of the latter fragments by size and charge in the
orthogonal IM dimension (pseudo-4D UPLC-ISD-IM-MS approach) enabled clear
detection and identification of the positional isomers formed upon PEGylation.
The results showed a highly heterogeneous mixture of singly and multiply
conjugated isomers plus unconjugated material. PEGylation was observed on all
three possible attachment sites (epsilon-NH2 of LysB29, A- and B-chain N
termini). Each PEGylation site was validated by analysis of the same product
after disulfide bond cleavage, so that the PEGylated A- and B- chain could be
individually characterized with the same pseudo-4D UPLC-ISD-IM-MS method.
PMID- 29329708
TI - Detection of native proteins using solid-substrate electrospray ionization mass
spectrometry with nonpolar solvents.
AB - Detection of native proteins, particularly directly from raw biological samples,
has been a challenging task for mass spectrometry. In this study, we demonstrated
that solid-substrate electrospray ionization mass spectrometry with nonpolar
solvents such as n-hexane could allow detection of native proteins and protein
complexes directly from raw biological samples. Mechanistic study revealed that
the process involved rapid vaporization of the nonpolar solvent, temperature
reduction of substrate surface, condensation of water from the ambient air, and
spray ionization of the condensed water with analytes under the electric field.
The fine spray with water at low temperature allowed the technique to detect
native proteins, even directly from viscous samples (e.g., egg white) and solid
samples (e.g., bone marrow). This study sheds new insight into the sampling and
ionization process of mass spectrometry and provides a technique of great
potential for characterization of proteins.
PMID- 29329710
TI - Hydride generation coupled with thioglycolic acid coated gold nanoparticles as
simple and sensitive headspace colorimetric assay for visual detection of
Sb(III).
AB - Antimony (Sb) is a toxic element which causes different health problems including
cardiac problems and lung cancer in humans, and its levels in surface water can
be noticeably increased to 100 MUg/L typically in the proximity of anthropogenic
sources. Thus, besides instrumental techniques, it is of great significance to
develop a simple, sensitive and selective analytical method for direct analysis
of Sb(III) at trace level without the need of any expensive and/or complicated
instrumentations and sample preparation processes. Herein, a simple and sensitive
headspace colorimetric assay was developed for the detection of Sb(III) by
hydride generation coupled with thioglycolic acid functionalized gold
nanoparticles (TGA-AuNPs). Sb(III) in the 30 mL sample solution was converted
into its volatile form (SbH3) through hydride generation reaction and headspace
extracted into 100 MUL chromogenic reagent, which contains methanol as extractant
and TGA-AuNPs as nanosensors, leading to aggregation of TGA-AuNPs and therefore a
red-to-blue color change. Parameters influencing the chromogenic and hydride
generation reactions were optimized. Addition of 300 MUM ethylenediamine
tetraacetic acid (EDTA) as masking agent largely suppressed the inferences from
mercury and arsenic. The proposed method can tolerate at least 10-fold As(III)
and 100-fold other metal ions including Hg(II). The detection limits were 6.0 and
1.2 MUg/L Sb(III) by naked-eye and UV-Vis spectrometer, respectively, which meet
the maximum admissible level in drinking water (6 MUg/L) set by the United States
Environmental Protection Agency. The feasibility of the proposed method was
demonstrated by rapid detection of Sb(III) in river water, lake water, ground
water and sea water samples by naked-eye at a spiking level of 6 MUg/L Sb(III).
PMID- 29329711
TI - Colorimetric logic gate for alkaline phosphatase based on copper (II)-based metal
organic frameworks with peroxidase-like activity.
AB - Nanozymes have been extensively exploited in the construction of colorimetric
sensors in the past decade. However, as lack of specific recognition element,
these sensors are mostly limited in the detection of hydrogen peroxide and its
related agents. In this work, a colorimetric assay for the detection of alkaline
phosphatase (ALP) activity was developed by employing copper (II)-based metal
organic frameworks (Cu-MOFs) as peroxidase mimic and pyrophosphate (PPi) as
recognition element. Benefiting from its intrinsic porosity, Cu-MOFs built from
one-step self-assembly showed a superior catalytic activity over horseradish
peroxidase. It was found that, in the presence of PPi, the catalytic activity of
Cu-MOFs was greatly inhibited due to the ultrastrong binding ability of Cu2+ with
PPi, and no colorimetric signal was recorded. However, after incubation with ALP,
such negative behavior of PPi can be suppressed as the hydrolysis of PPi into
orthophosphates (Pi) with low affinity to Cu2+, producing a colorimetric signal
depending on ALP level. On this basis, a way for quantitative analysis of ALP
activity was paved accordingly. Compared with previously reported ALP assays
based on nanomaterials, this assay is simple, cost-effective and visualized,
which not only allows highly sensitive analysis of ALP activity with a detection
limit of 0.19 U/L, but also exhibits a good sensing performance in serum samples.
Furthermore, based on the distinct colorimetric signals induced by PPi and ALP,
an IMPLICATION logic gate was constructed. We hope that this study could provide
a new insight for designing nanozyme-based highly specific colorimetric sensors.
PMID- 29329712
TI - Risk Factors and Frequency of Ingrown Nails in Adult Diabetic Patients.
AB - The present study evaluated the properties of nails, frequency of ingrown nails
in patients with type 2 diabetes mellitus (DM), risk factors for developing
ingrown nails, and effect of diabetic polyneuropathy and vasculopathy on the
development and outcome of ingrown nails. Our 6-month epidemiologic prospective
study included 300 patients with type 2 DM attending a DM outpatient clinic for
routine examinations. The general characteristics and foot changes of the study
population were investigated. Diabetic polyneuropathy and vasculopathy were
evaluated using a biothesiometer, monofilament tests, and arterial Doppler
ultrasonography. The frequency of ingrown nails was 13.6%. Multivariate analysis
with logistic regression showed that body mass index (odds ratio [OR] 1.077, 95%
confidence interval [CI] 1.007 to 1.15; p = .03), previous trauma (OR 2.828, 95%
CI 1.017 to 7,867, p = .042), a weak dorsalis pedis pulse (OR 2.72, 95% CI 1.17
to 6.30, p = .02), trimming type (OR 2.3, 95 CI 1.06 to 4.98), p = .35),
onychogryphosis (OR 9.036, 95% CI 2.34 to 34.87, p = .001), and subungual
hyperkeratosis (OR 4.3, 95% CI 1.99 to 9.3, p = .001) were predictive variables
for ingrown nails in our population. The incidence of onychomycosis was
significantly greater in patients with ingrown nails (p = .032) than in patients
without ingrown nails. The nail curvature ratio was greater in the patients with
ingrown nails than in the group with normal nails. Arterial Doppler ultrasound
examinations showed peripheral arterial disease in 19 patients (46.9%) with
ingrown nails. The prevalence of ingrown nails was greater in the patients with
DM than in the healthy population. Our results indicate that nail type, nail
morphology, and diabetic vasculopathy affect the formation and evolution of
ingrown nails.
PMID- 29329713
TI - Baseline and pre-operative 1-year mortality risk factors in a cohort of 509 hip
fracture patients consecutively admitted to a co-managed orthogeriatric unit
(FONDA Cohort).
AB - INTRODUCTION: The aim of this study was to determine the patient characteristics
that predict 1-year mortality after a hip fracture (HF). METHODS: All patients
admitted consecutively with fragility HF during 1 year in a co-managed
orthogeriatric unit of a university hospital (FONDA cohort) were assesed.
Baseline and admission demographic, clinical, functional, analytical and body
composition variables were collected in the first 72 h after admission. A
protocol designed to minimize the consequences of the HF was applied. One year
after the fracture patients or their carers were contacted by telephone to
ascertain their vital status. RESULTS: A total of 509 patients with a mean age of
85.6 years were included. One-year mortality was 23.2%. The final multivariate
model included 8 independent mortality risk factors: age >85 years, baseline
functional impairment in basic activities of daily living, low body mass index,
cognitive impairment, heart disease, low hand-grip strength, anaemia at
admission, and secondary hyperparathyroidism associated with vitamin D
deficiency. The association of several of these factors greatly increased
mortality risk, with an OR (95% confidence interval [CI]) of 5.372 (3.227-8.806)
in patients with 4 to 5 factors, and an OR (95% CI) of 11.097 (6.432-19.144) in
those with 6 or more factors. CONCLUSIONS: In addition to previously known
factors (such as age, impairment in basic activities of daily living, cognitive
impairment, malnutrition and anaemia at admission), other factors, such as muscle
strength and hyperparathyroidism associated with vitamin D deficiency, are
associated with greater 1-year mortality after a HF.
PMID- 29329714
TI - Mutation burden profile in familial Alzheimer's disease cases from India.
AB - This study attempts to identify coding risk variants in genes previously
implicated in Alzheimer's disease (AD) pathways, through whole-exome sequencing
of subjects (N = 17) with AD, with a positive family history of dementia
(familial AD). We attempted to evaluate the mutation burden in genes encoding
amyloid precursor protein metabolism and previously linked to risk of dementias.
Novel variants were identified in genes involved in amyloid precursor protein
metabolism such as PSEN1 (chr 14:73653575, W161C, tgg > tgT), PLAT (chr
8:42039530,G272R), and SORL1 (chr11:121414373,G601D). The mutation burden
assessment of dementia-related genes for all 17 cases revealed 45 variants, which
were either shared across subjects, or were present in just the 1 patient. The
study shows that the clinical characteristics, and genetic correlates, obtained
in this sample are broadly comparable to the other studies that have investigated
familial forms of AD. Our study identifies rare deleterious genetic variations,
in the coding region of genes involved in amyloid signaling, and other dementia
associated pathways.
PMID- 29329715
TI - Ten questions you should consider before submitting an article to a scientific
journal.
AB - Investigating involves not only knowing the research methods and designs; it
involves knowing the strategies for disseminating and publishing the results in
scientific journals. An investigation is considered complete when it is published
and is disclosed to the scientific community. The publication of a manuscript is
not simple, since it involves examination by a rigorous editorial process
evaluator to ensure the scientific quality of the proposal. The objective of this
article is to communicate to potential authors the main errors or deficiencies
that typically and routinely explain the decision by the referees of scientific
journals not to accept a scientific article. Based on the experience of the
authors as referees of national and international journals in the field of
nursing and health sciences, we have identified a total of 10 types or groups,
which cover formulation errors, inconsistencies between different parts of the
text, lack of structuring, imprecise language, information gaps, and the
detection of relevant inaccuracies. The identification and analysis of these
issues enables their prevention, and is of great use to future researchers in the
dissemination of the results of their work to the scientific community. In short,
the best publishing strategy is one that ensures the scientific quality of the
work and spares no effort in avoiding the errors or deficiencies that referees
routinely detect in the articles they evaluate.
PMID- 29329716
TI - Gelatin- hydroxyapatite- calcium sulphate based biomaterial for long term
sustained delivery of bone morphogenic protein-2 and zoledronic acid for
increased bone formation: In-vitro and in-vivo carrier properties.
AB - In this study, a novel macroporous composite biomaterial consisting of gelatin
hydroxyapatite-calcium sulphate for delivery of bone morphogenic protein-2 (rhBMP
2) and zoledronic acid (ZA) has been developed. The biomaterial scaffold has a
porous structure and functionalization of the scaffold with rhBMP-2 induces
osteogenic differentiation of MC3T3-e1 cells seen by a significant increase in
biochemical and genetic markers of osteoblastic differentiation. In-vivo muscle
pouch experiments showed higher mineralization using scaffold+rhBMP-2 when
compared to an approved absorbable collagen sponge (ACS)+rhBMP-2 as verified by
micro-CT. Co-delivery of rhBMP-2+ZA via the novel scaffold enabled a reduction in
the effective rhBMP-2 doses. The presence of tartrate resistant acid phosphatase
staining in the rhBMP-2 group indicates osteoclastic resorption, which could be
stalled by adding ZA, which by speculation could explain the net increase in
mineralization. The new scaffold allowed for slow release of rhBMP-2 in-vitro
(3.3+/-0.1%) after 4weeks. Using single photon emission computed tomography
(SPECT), the release kinetics of 125I-rhBMP-2 in-vivo was followed for 4weeks and
a total of 65.3+/-15.2% 125I-rhBMP-2 was released from the scaffolds. In-vitro
14C-ZA release curve shows an initial burst release on day 1 (8.8+/-0.7%)
followed by a slow release during the following 4weeks (13+/-0.1%). In-vivo, an
initial release of 43.2+/-7.6% of 14C-ZA was detected after 1day, after which the
scaffold retained the remaining ZA during 4-weeks. Taken together, our results
show that the developed biomaterial is an efficient carrier for spatio-temporal
delivery of rhBMP-2 and ZA leading to increased bone formation compared to
commercially available carrier for rhBMP-2.
PMID- 29329717
TI - Erratum.
PMID- 29329718
TI - Erratum.
PMID- 29329719
TI - Regulatory Potential of the RNA Processing Machinery: Implications for Human
Disease.
AB - Splicing and nuclear export of mRNA are critical steps in the gene expression
pathway. While RNA processing factors can perform general, essential functions
for intron removal and bulk export of mRNA, emerging evidence highlights that the
core RNA splicing and export machineries also display regulatory potential. Here,
we discuss recent insights into how this regulatory potential can selectively
alter gene expression and regulate important biological processes. We also
highlight the participation of RNA processing pathways in the cellular response
to DNA damage at multiple levels. These findings have important implications for
the contribution of selective mRNA processing and export to the development of
human cancers and neurodegenerative disorders.
PMID- 29329721
TI - Quantifying fluctuation in glucose levels to identify early changes in glucose
homeostasis in cystic fibrosis.
AB - BACKGROUND: Cystic fibrosis related diabetes (CFRD) is associated with increased
morbidity in CF. Variability in physiological systems is associated with
dysfunctional homeostasis. We examined whether fluctuation in glucose is a marker
of CFRD or "pre-diabetes". METHODS: Using a machine learning approach, we
compared glucose IQR to current diagnostic criteria in a review of continuous
glucose monitoring data. RESULTS: Analysis was performed on 248 studies from 142
children. Calculated IQR (cIQR) was increased between children with CFRD, normal
glucose homeostasis and indeterminate status (p<0.0001) and impaired glucose
tolerance (p<0.05, Kruskal-Wallis test). In subjects who developed CFRD (n=20),
cIQR increased between baseline and diagnosis (1.4mmol/L versus 2.4mmol/L,
p<0.0001, Wilcoxon test). Area under the curve for CFRD on the basis of cIQR was
0.865 (p<0.0001). Neither episodes of hypoglycaemia nor cIQR at baseline
predicted CFRD. CONCLUSIONS: Glucose fluctuation on CGMS can be quantified by
calculating the IQR. This information may improve early recognition of abnormal
glucose homeostasis.
PMID- 29329722
TI - Long-term Average Speech Spectra of Postlingual Cochlear Implant Users.
PMID- 29329720
TI - Discoveries of Extrachromosomal Circles of DNA in Normal and Tumor Cells.
AB - While the vast majority of cellular DNA in eukaryotes is contained in long linear
strands in chromosomes, we have long recognized some exceptions like
mitochondrial DNA, plasmids in yeasts, and double minutes (DMs) in cancer cells
where the DNA is present in extrachromosomal circles. In addition, specialized
extrachromosomal circles of DNA (eccDNA) have been noted to arise from repetitive
genomic sequences like telomeric DNA or rDNA. Recently eccDNA arising from unique
(nonrepetitive) DNA have been discovered in normal and malignant cells, raising
interesting questions about their biogenesis, function and clinical utility.
Here, we review recent results and future directions of inquiry on these new
forms of eccDNA.
PMID- 29329723
TI - Prolonged Grief and Cognitive Decline: A Prospective Population-Based Study in
Middle-Aged and Older Persons.
AB - OBJECTIVE: Bereavement can result in unresolved and prolonged grief, often termed
prolonged grief disorder (PGD). The impact of PGD on cognitive functioning is
poorly understood. The aim of the study was to compare the cognitive decline,
assessed by repeated measures of different cognition domains, between persons
with normal and PGD and a non-grieving reference population in a 7-year follow-up
study. METHODS: The study sample comprised 3126 non-demented persons, mean age:
64 years, of the Rotterdam Study. Participants were classified into three groups:
no grief (reference group, N = 2,582), normal grief (N = 418), and prolonged
grief disorder (N = 126). Participants were assessed with the Complicated Grief
Inventory and underwent cognitive testing (Mini-Mental State Examination [MMSE],
Letter-Digit Substitution test, Stroop test, Word fluency task, Word learning
test). Analyses were adjusted for baseline cognition and depressive symptoms;
persons with major depressive disorders were excluded. RESULTS: Compared with the
reference group, participants with PGD showed a decrease in global cognitive
function, MMSE scores, and World learning test (immediate and delayed) over time.
Participants with normal grief did not show a stronger cognitive decline in any
of cognitive tests than the reference group. CONCLUSIONS: Participants with PGD
showed a stronger cognitive decline than the reference group during 7 years of
follow-up. This suggests that PGD is a risk factor for cognitive decline, but
this study cannot detect the psychobiological mechanism underlying this
longitudinal association.
PMID- 29329724
TI - The Potential of Cold Plasma for Safe and Sustainable Food Production.
AB - Cold plasma science and technology is increasingly investigated for translation
to a plethora of issues in the agriculture and food sectors. The diversity of the
mechanisms of action of cold plasma, and the flexibility as a standalone
technology or one that can integrate with other technologies, provide a rich
resource for driving innovative solutions. The emerging understanding of the
longer-term role of cold plasma reactive species and follow-on effects across a
range of systems will suggest how cold plasma may be optimally applied to
biological systems in the agricultural and food sectors. Here we present the
current status, emerging issues, regulatory context, and opportunities of cold
plasma with respect to the broad stages of primary and secondary food production.
PMID- 29329725
TI - Aquagenic urticaria: Severe extra-cutaneous symptoms following cold water
exposure.
PMID- 29329726
TI - Patient-centered communication of community treatment assistants in Tanzania
predicts coverage of future mass drug administration for trachoma.
AB - OBJECTIVE: Prevention of Trachoma, the leading cause of infectious blindness,
requires community treatment assistants (CTAs) to perform mass drug
administration (MDA) of azithromycin. Previous research has shown that female
CTAs have higher MDA coverage, but no studies have focused on the content of
conversation. We hypothesize that female CTAs had more patient-centered
communication and higher MDA coverage. METHODS: In 2011, CTAs from 23
distribution sites undergoing MDA as part of the Partnership for Rapid
Elimination of Trachoma were selected. CTA - villager interactions were audio
recorded. Audio was analyzed using an adaptation of the Roter Interaction
Analysis System. The outcome of interest was the proportion of adults receiving
MDA in 2011 who returned in 2012. RESULTS: 58 CTAs and 3122 interactions were
included. Sites with female CTAs had significantly higher patient-centeredness
ratio (0.548 vs 0.400) when compared to sites with male CTAs. Sites with more
patient-centered interactions had higher proportion of patients return (p =
0.009). CONCLUSION: Female CTAs had higher proportion of patient-centered
communication. Patient centered communication was associated with higher rates of
return for MDA. PRACTICE IMPLICATIONS: Greater patient-centered connection with
health care providers affects participation in public health efforts, even when
those providers are lay health workers.
PMID- 29329727
TI - Parent activation in the pediatric emergency department: Theory vs. reality.
AB - OBJECTIVE: To measure parent activation and test for its associations with
sociodemographics, clinical factors, and short-term outcomes. METHODS: By
convenience sampling, 246 parents of children treated in an emergency department
(ED) of a children's hospital completed the Parent-Patient Activation Measure (P
PAM) and answered sociodemographic questions. Clinical information was abstracted
from medical records. Phone calls to parents and primary care physician offices
were conducted within one-month post-ED visit for information about short-term
outcomes. RESULTS: We discovered higher than expected activation among our sample
(mean = 73), higher activation scores by Spanish language and child chronic
illness status, and associations between activation scores and ED visit and
discharge instruction comprehension and filling prescriptions (short-term
outcomes). However, the theory of parent activation did not adequately fit the
data. CONCLUSION: Before the P-PAM in pediatric clinical care becomes widespread,
further research is necessary to better understand parent activation and its
associations with pediatric outcomes. PRACTICE IMPLICATIONS: Although the PAM has
shown promise in accurately measuring patient activation across various
populations and disease processes, the same is not yet true of the P-PAM. To
date, pediatric studies using the P-PAM have called its psychometric properties
into question. Further research is needed to understand and measure parent
activation.
PMID- 29329728
TI - Gene expression patterns associated with human placental trophoblast
differentiation.
AB - Cell fusion is a hallmark of placental trophoblast cell differentiation and the
mature syncytiotrophoblasts play essential roles for fetal-maternal exchange and
production of pregnancy-related hormones. Using a well-established in vitro
trophoblast differentiation model, we performed a microarray analysis on mRNA
expression in trophoblast and syncytiotrophoblast cell cultures. Dramatic changes
in gene expression patterns were detected during trophoblast differentiation.
Real-time PCR analysis confirmed the reliability of the microarray data. As many
as 3524 novel and known genes have been found to be up- or down-regulated for >2
fold. A number of cell cycle regulator including CDC6, CDC20, Cyclins B2, L1 and
E2, were down-regulated in the syncytiotrophoblast, providing a mechanism for the
loss of mitotic activity during trophoblast differentiation. Further
characterization on the identified genes may lead to better understanding of
placental patho-physiology in obstetric diseases such as preeclampsia.
PMID- 29329729
TI - Elevated neuron-specific enolase and S100 calcium-binding protein B
concentrations in cerebrospinal fluid of patients with anti-N-methyl-d-aspartate
receptor encephalitis.
AB - BACKGROUND: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a
relatively common autoimmune neurological disease of the central nervous system
(CNS). Neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B)
are structural proteins of the central nervous system (CNS). In patients with CNS
injury accompanied by nervous tissue and cellular damage, these structural
proteins are released from cells; their extracellular concentrations, including
those in cerebrospinal fluid (CSF) and blood, subsequently increase. METHODS:
Thirty-six patients with anti-NMDAR encephalitis were prospectively recruited.
The CSF NSE and S100B concentrations were measured in 19 and 17 patients,
respectively. The CSF NSE and S100B concentrations were measured in 21 patients
with noninflammatory neurological disease as controls. All measurements were
performed using enzyme-linked immunosorbent assays. RESULTS: The CSF NSE and
S100B concentrations were remarkably higher in the patients with anti-NMDAR
encephalitis than in the controls. The early NSE or S100B concentrations in CSF
were associated with the mRS. CONCLUSION: CSF NSE and S100B concentration in
patients with anti-NMDAR encephalitis is higher than in patients with non
inflammatory neurological disease. The early NSE or S100B concentrations in CSF
were associated with the mRS and we can use it to determine the prognosis of the
disease.
PMID- 29329730
TI - Mechanical thrombectomy in acute ischaemic stroke: a review of the different
techniques.
AB - Endovascular mechanical thrombectomy (MT) is reserved for acute ischaemic stroke
secondary to large vessel occlusion. The various MT techniques employed in the
treatment of hyperacute strokes are constantly evolving with new devices and
improvisation of existing technology (Wahlgren, et al 2016). In this review, we
describe a variety of MT techniques gained from our experience of performing over
350 procedures in 7 years of providing a 24/7 service within the national
framework of a hyperacute stroke centre. We outline a number of endovascular
techniques, procedure limitations, and potential complications.
PMID- 29329731
TI - Multimodality imaging evaluation before transcatheter aortic valve implantation:
incidence of contrast medium-induced acute kidney injury, risk factors and
prognosis.
AB - AIM: To evaluate the incidence, risk factors, and prognostic implications of
contrast medium-induced acute kidney injury (CI-AKI) in patients undergoing
transcatheter aortic valve implantation (TAVI) evaluation. MATERIALS AND METHODS:
Datasets from 98 out of 207 consecutive patients referred for multidetector
computed tomography (MDCT) for TAVI evaluation were eligible for evaluation and
were analysed retrospectively. The incidence of CI-AKI was correlated to outcome
and to potential risk factors: kidney function (estimated glomerular filtration
rate [eGFR]), heart failure, diabetes, amount of contrast medium, and duration of
examination period. RESULTS: CI-AKI occurred in 67 patients (68.4%) and mainly
correlated with eGFR (p=0.01) and the amount of contrast medium as a function of
eGFR (p=0.04). CI-AKI occurred before TAVI in 36 (53.7%) patients of which 13
(19.4%) did not undergo TAVI. In-hospital all-cause mortality was 21.4%, and of
those 21 patients, 18 (85.7%) had CI-AKI and nine (42.9%) did not undergo TAVI.
One-year all-cause mortality was 39.8%, and of those 39 patients who died within
1 year, 31 (79.5%) had CI-AKI. CONCLUSION: CI-AKI mostly occurs already before
TAVI as a consequence of pre-procedural imaging, which therefore represents the
main contributor for CI-AKI in relation to TAVI. Regarding the observation that
some patients will ultimately have no benefit because TAVI is not performed and
the poor prognosis linked to CI-AKI should encourage improvement in patient
selection when referring to pre-procedural imaging.
PMID- 29329732
TI - Changes in quantitative CT image features of ground-glass nodules in
differentiating invasive pulmonary adenocarcinoma from benign and in situ
lesions: histopathological comparisons.
AB - AIM: To evaluate progressive changes in quantitative CT features of the non-solid
component of ground-glass nodules (GGNs) from baseline to follow-up to
differentiate invasive (minimally invasive adenocarcinoma [MIA] and invasive
adenocarcinoma [IA]) GGNs from benign or pre-invasive (adenocarcinoma in situ
[AIS]) lesions. MATERIALS AND METHODS: Patients with a GGN detected at baseline
and follow-up computed tomography (CT), examined by tissue sampling were included
in the study. The diameter and mean, maximum, minimum CT density and density
deviation from the non-solid component of whole GGNs were measured. Progression
of these features over time was analysed by linear regression analysis.
Multivariate receiver operating characteristics analyses of combined measures
created by a logistic regression model were performed to evaluate diagnostic
performance for invasive GGNs. RESULTS: Sixty-one patients (24 males) with 70
GGNs were included. Fifteen GGNs were benign, six AIS, 38 MIA, and 11 IA. The
mean diameter of all histological subtypes increased from baseline to follow-up,
the largest increase was found in the MIA group (p<0.001). For MIA and IA, the
mean, maximum, minimum density, and density deviation had a positive correlation
over time, whilst benign and pre-invasive GGNs showed a negative correlation for
these features. A diagnostic model based on three GGN features (increasing in
diameter, mean density, and density deviation) identified invasive GGNs with a
sensitivity, specificity and area under the receiver operating characteristic
(ROC) curve (AUC) of 83.7%, 61.9%, and 0.786, respectively (p<0.001). CONCLUSION:
In GGN follow-up, the diameter of benign and AIS, and invasive GGNs significantly
increased. Additional analysis of mean density and density deviation in the non
solid component may help to identify invasive GGNs.
PMID- 29329733
TI - Association between leukoaraiosis and cerebral blood flow territory alteration in
asymptomatic internal carotid artery stenosis.
AB - AIM: To test the hypothesis that leukoaraiosis (also known as white matter
lesion) is associated with cerebral blood flow territory change as revealed by
territorial arterial spin-labeling (TASL) magnetic resonance imaging (MRI) in
patients with asymptomatic internal carotid artery stenosis (aICAS). MATERIALS
AND METHODS: The institutional review board approved this study. Thirty-three
patients with aICAS were included prospectively and divided into high-grade
(ultrasonographic stenosis >=70%, n=17) and low-grade (n=16) groups; 16 healthy
subjects were also included. Cerebral flow territory was delineated for left ICA,
right ICA, and vertebral arteries using TASL MRI and fuzzy clustering. Two
licensed neuroradiologists independently and dichotomously rated the
hemispherical asymmetry of flow territories. Flow territories were finalised by
consensus, and when asymmetry was present, these were divided into normal and
abnormal areas where the raters separately assessed leukoaraiosis based on fluid
attenuated inversion recovery images and the Fazekas scale. RESULTS: The inter
rater agreement in the evaluation of flow territory asymmetry with TASL imaging
in conjunction with time-of-flight angiogram is substantial (Cohen's kappa=0.82).
Multinomial logistic regression (reference group=healthy subjects) indicates that
global leukoaraiosis is not a predictor of aICAS after controlling for age,
whereas in high-grade patients, the deep white matter lesion is more severe in
the area receiving collateral circulation than in the area with normal flow
territory (Wilcoxon signed-rank test, p=0.03). CONCLUSION: TASL MRI is clinically
feasible in aICAS and shows that more severe deep white matter lesions are
associated with collateral circulation in high-grade patients.
PMID- 29329734
TI - The morphological changes of bronchovascular bundles within subsolid nodules on
HRCT correlate with the new IASLC classification of adenocarcinoma.
AB - AIM: To observe the morphological changes of bronchovascular bundles within
subsolid nodules on high-resolution (HR) computed tomography (CT) and analyse the
correlation with the new adenocarcinoma classification. MATERIALS AND METHODS:
Two hundred and sixteen lesions (absent consolidation on mediastinal window) were
reviewed retrospectively. CT features including dimensions, contour,
morphological changes of the blood vessels, and bronchi/bronchioles, vacuole
signs, and their correlation with histopathology were evaluated. RESULTS:
Excluding nine non-cancerous lesions, 34 pre-invasive lesions (PILs) including 15
atypical adenomatous hyperplasias (AAHs) and 19 adenocarcinomas in situ (AISs),
21 minimally invasive adenocarcinomas (MIAs), and 152 invasive adenocarcinomas
(IACs) were analysed. Lepidic, acinar, and papillary patterns were identified in
this cohort of adenocarcinomas. IACs were grouped into three types: type I
(lepidic pattern >=80%, n=47), type II (lepidic pattern >=50%, <80%, n=67), and
type III (lepidic pattern <50%, n=38). The contour of lesions, and morphological
changes in vessels and bronchi/bronchioles significantly correlated with the
classification of PIL, MIA, and IACs (p=0.000, p=0.000, and p=0.017,
respectively). In IACs, the prevalence of vascular abnormalities on HRCT
significantly correlated with (p=0.000) the proportion of non-lepidic pattern
(23.40% in type I, 58.21% in type II, and 76.32% in type III); the prevalence of
bronchial/bronchiolar abnormalities was higher (p=0.008) in type II/III (20.95%)
compared with type I (6.38%). CONCLUSIONS: The morphological changes of vessels
and bronchi/bronchioles within the subsolid nodules on HRCT help to differentiate
IAC from PIL and MIA, and are more common in non-lepidic predominant
adenocarcinomas.
PMID- 29329736
TI - Research on Adolescent Sexuality Should Be Inclusive of Disability.
PMID- 29329737
TI - The Authors reply.
PMID- 29329735
TI - Diagnostic value of early postoperative MRI and diffusion-weighted imaging
following trans-sphenoidal resection of non-functioning pituitary macroadenomas.
AB - AIM: To establish the value of early contrast-enhanced magnetic resonance imaging
(MRI) and diffusion-weighted imaging (DWI) in differentiating residual pituitary
adenoma from postoperative surgical changes. MATERIALS AND METHODS: Thirty
patients with non-functioning pituitary macroadenomas, who were undergoing trans
sphenoidal adenomectomy, were prospectively studied. Patients were imaged with
both MRI and DWI in the early postoperative period, as well as 6-months post
surgery. Patterns of postoperative contrast enhancement were described (non
enhancement, peripheral enhancement, and nodular enhancement). Apparent diffusion
coefficient (ADC) maps were utilised to select the region of interest (ROI) for
ADC calculations. RESULTS: Seventeen patients had postoperative surgical
granulation tissue and 13 had residual adenoma based on the 6 months follow-up
imaging. Mean ADC values of postoperative granulation tissue and residual adenoma
were 1.476+/-0.476*10-3 mm2/s and 0.855+/-0.190*10-3 mm2/s, respectively, in the
early postoperative period, and 1.357+/-0.416*10-3 mm2/s and 0.829+/-0.201*10-3
mm2/s, respectively, at the 6-month follow-up. ADC values of granulation tissue
were significantly different from that of residual adenoma at both time points
(p<0.001). Sensitivity, specificity, positive and negative predictive values of
early MRI were 84.6%, 94.1%, 91.7%, and 88.9% respectively, and of early DWI were
91%, 97%, 94.3%, and 93%, respectively. CONCLUSION: Early postoperative DWI after
trans-sphenoidal resection of pituitary macroadenomas may be more helpful than
early MRI in differentiating residual adenoma from post-surgical changes.
PMID- 29329738
TI - Relationship Between Proprioception and Endurance Functionality of the Cervical
Flexor Muscles in Chronic Neck Pain and Asymptomatic Participants.
AB - OBJECTIVE: The purpose of this study was to compare the relationship between
flexion endurance capacity and joint position error in participants with or
without chronic neck pain (CNP). METHODS: Sixty-one CNP and 60 asymptomatic
volunteers participated in this cross-sectional, case-control, and correlational
analysis study. The measured variables included absolute and constant joint
repositioning errors in the sagittal and horizontal directions, clinical flexor
endurance test score, pain intensity, and neck disability index. RESULTS: The
groups did not statistically differ in flexion endurance (P > .05). The CNP group
had a smaller absolute error on the right (P < .01) and left (P = .01) rotation
and an overshooting error pattern in the flexion direction (P < .05). But the
asymptomatic group did not exhibit any over-/undershooting pattern tendency (P >
.05). Although flexion endurance was not correlated with any of the joint
repositioning error components in either group, pain and disability scores were
significantly correlated with left rotation absolute error (r = -0.34 and rho =
0.37, respectively). CONCLUSION: The clinical cervical flexor endurance test,
ignoring the relative contribution of the deep and superficial groups of muscles,
may not efficiently characterize CNP patients.
PMID- 29329739
TI - Association Between Symptoms of Central Sensitization and Cognitive Behavioral
Factors in People With Chronic Nonspecific Low Back Pain: A Cross-sectional
Study.
AB - OBJECTIVE: The objective of this cross-sectional study was to analyze the
relationship between symptoms of central sensitization (CS) and important
cognitive behavioral and psychosocial factors in a sample of patients with
chronic nonspecific low back pain. METHODS: Participants with chronic nonspecific
low back pain for at least 3 months were included in the study. They completed
several questionnaires and a functional test. Pearson's correlation was used to
analyze associations between symptoms of CS and pain behavior, functioning, pain,
pain catastrophizing, kinesiophobia, and illness perceptions. Additionally, a
between-group analysis was performed to compare patients with and without
clinically relevant symptoms of CS. RESULTS: Data from 38 participants were
analyzed. Significant associations were found between symptoms of CS and all
other outcomes, especially current pain (r = 0.510, P = .001), mean pain during
the past 7 days (r = 0.505, P = .001), and pain catastrophizing (r = 0.518, P =
.001). Patients with clinically relevant symptoms of CS scored significantly
worse on all outcomes compared with persons without relevant symptoms of CS,
except on functioning (P = .128). CONCLUSIONS: Symptoms of CS were significantly
associated with psychosocial and cognitive behavioral factors. Patients
exhibiting a clinically relevant degree of symptoms of CS scored significantly
worse on most outcomes, compared with the subgroup of the sample with fewer
symptoms of CS.
PMID- 29329740
TI - Criteria to Screen for Traumatic Cervical Spine Instability: A Consensus of
Chiropractic Radiologists.
AB - OBJECTIVE: The purpose of this study was to establish consensus on a radiographic
definition for cervical instability for routine use in chiropractic patients who
sustain trauma to the cervical spine. METHOD: We conducted a modified Delphi
study with a panel of chiropractic radiologists. Panelists were asked to rate
potential screening criteria for traumatic cervical spine instability when
assessing cervical spine radiographs. Items rated as important for inclusion by
at least 60% of participants in round 1 were submitted for a second round of
voting in round 2. Items rated for inclusion by at least 75% of the participants
in round 2 were used to create the consensus-based list of screening criteria.
Participants were asked to vote and reach agreement on the final screening
criteria list in round 3. RESULTS: Twenty-nine chiropractic radiologists
participated in round 1. After 3 rounds of survey, 85% of participants approved
the final consensus-based list of criteria for traumatic cervical spine
instability screening, including 6 clinical signs and symptoms and 5 radiographic
criteria. Participants agreed that the presence of 1 or more of these clinical
signs and symptoms and/or 1 or more of the 5 radiographic criteria on routine
static radiographic studies suggests cervical instability. CONCLUSION: The
consensus-based radiographic definition of traumatic cervical spine instability
includes 6 clinical signs and symptoms and 5 radiographic criteria that doctors
of chiropractic should apply to their patients who sustain trauma to the cervical
spine.
PMID- 29329741
TI - Sex differences of hippocampal structure in bipolar disorder.
AB - Although differential patterns in clinical characteristics have been consistently
noted between male and female patients with bipolar disorder (BD), the effect of
sex on the hippocampal structure remains unclear. To address this, the present
study investigated the effects of BD and sex on the hippocampal structure, and
the relationship between the hippocampal structure and cognitive performance.
Morphometric and neurocognitive analyses were performed in 91 subjects (patients
with BD: male/female = 33/19; normal controls: male/female = 22/17). Patients had
significantly decreased left parahippocampal gyrus area and left/right
hippocampal volume compared to normal controls. Within the BD group only, female
patients presented with smaller right hippocampal volume than males. In the
Spatial Span (SS) test (used to assess working memory capacity) and the Maze test
(used to evaluate the ability to anticipate), patients demonstrated decreased
performance compared to normal controls, with a significant main effect of sex.
Left parahippocampal gyrus area and right hippocampal volume were positively
correlated with SS and Maze in patients; moreover, right hippocampal volume
predicted 17.4% of SS performance variance. These results suggest that there may
be a difference between male and female patients with regard to right hippocampal
volume, and that female patients may need more attention than males.
PMID- 29329742
TI - Frontal activity measured by near-infrared spectroscopy in patients taking
different atypical antipsychotic drugs: A cross-sectional study.
AB - Using near-infrared spectroscopy, we examined changes in the concentration of
oxygenated hemoglobin ([oxy-Hb]) in the frontal lobe during a verbal fluency task
in 20 patients with schizophrenia (10 patients each receiving olanzapine [OLZ]
and risperidone [RIS]) and 10 healthy controls. We found that [oxy-Hb] levels in
the prefrontal region were higher in the patients receiving OLZ than in those
receiving RIS. These results suggest that antipsychotic drugs have different
effects on cerebral hemodynamic patterns, which may reflect frontal lobe
function. Further studies with a larger sample size are needed to verify our
preliminary findings.
PMID- 29329744
TI - Letter to the Editor regarding "Use of both anterograde and retrograde internal
mammary vessels in the bipedicled deep inferior epigastric perforator flap for
unilateral breast reconstruction".
PMID- 29329743
TI - GABA and glutamate in children with Tourette syndrome: A 1H MR spectroscopy study
at 7T.
AB - Tourette syndrome (TS) is characterized by presence of chronic, fluctuating motor
and phonic tics. The underlying neurobiological basis for these movements is
hypothesized to involve cortical-striatal-thalamo-cortical (CSTC) pathways. Two
major neurotransmitters within these circuits are gamma-aminobutyric acid (GABA)
and glutamate. Seventy-five participants (32 with TS, 43 controls) ages 5-12
years completed 1H MRS at 7T. GABA and glutamate were measured in dorsolateral
prefrontal cortex (DLPFC), ventromedial prefrontal cortex (VMPFC), premotor
cortex (PMC), and striatum, and metabolites quantified using LCModel.
Participants also completed neuropsychological assessment emphasizing inhibitory
control. Scans were well tolerated by participants. Across ROIs combined,
glutamate was significantly higher in the TS group, compared to controls, with no
significant group differences in GABA observed. ROI analyses revealed
significantly increased PMC glutamate in the TS group. Among children with TS,
increased PMC glutamate was associated with improved selective motor inhibition;
however, no significant associations were identified between levels of glutamate
or GABA and tic severity. The dopaminergic system has long been considered to
have a dominant role in TS. Accumulating evidence, however, suggests involvement
of other neurotransmitter systems. Data obtained using 1H MRS at 7T supports
alteration of glutamate within habitual behavior-related CSTC pathways of
children with TS.
PMID- 29329745
TI - Poly(methyl methacrylate) salt as film forming material to design orodispersible
films.
AB - This work aims to evaluate the possible use of a poly(sodium methacrylate, methyl
methacrylate) (NaPMM2) plasticized by PEG400 in the design of orodispersible
films (ODF). Placebo ODF prepared by solvent casting were intended to study the
impact of the polymer/plasticizer ratio and residual moisture on disintegration
time, stickiness and mechanical properties. The drug loading capacity was
assessed using ketoprofen and paracetamol. Placebo ODF containing PEG400 in the
10-30% w/w range and 10-15% of residual moisture content were easy-to-handle,
packed without failures and completely dissolved within 30 s. NaPMM2/PEG400 in
80/20 ratio allowed up to 70% of paracetamol loading, which appeared as the
largest value described in literature. This ODF showed good mechanical properties
and disintegration time. The same formulation loaded with 25% or 50% ketoprofen
(pKa = 4.45) swelled without disintegrating, because of a partial protonation of
NaPMM2, as verified by ATR-FTIR spectroscopy. However, the addition of 5%
surfactants allowed the formulation of ODF containing 25% ketoprofen that
disintegrated within one minute and guaranteed the complete drug dissolution
within 5 min. All the presented data, discussed in the framework of information
available on such copolymer, highlighted its versatility in the design of
orodispersible dosage forms.
PMID- 29329746
TI - Evaluation of a transtympanic delivery system in Mus musculus for extended
release steroids.
AB - OBJECTIVE: The current investigation evaluated a novel extended release delivery
system for treating inner ear diseases. The platform technology consists of a
film forming agent (FFA) and microsphere component to localize and extend drug
delivery within the ear. STUDY DESIGN: Studies evaluated dissolution kinetics of
microspheres with multiple encapsulates, testing of a variety of FFAs, and
ability to localize to the round window membrane in mice in vivo. SETTING:
Studies were completed at Orbis Biosciences and The University of Kansas Medical
Center. SUBJECTS: In conjunction with in vitro characterization, an infrared dye
containing microsphere formulation was evaluated for round window membrane (RWM)
localization and general tolerability in C57/BL6 Mus musculus for 35 days.
METHODS: In vitro characterization was performed using upright diffusion cells on
cellulose acetate membranes, with drug content quantified by high performance
liquid chromatography. Mus musculus dosing of infrared dye-containing
microspheres was performed under anesthesia with a 27 GA needle and 2.0 MUL
injection volume RESULTS: In vitro dissolution demonstrates the ability of the
FFA with microsphere platform to release steroids, proteins, peptides, and
nucleic acids for at least one month, while necroscopy shows the ability of the
FFA with dye-loaded microspheres to remain localized to Mus musculus RWM for the
same period of time, with favorable tolerability. CONCLUSIONS: Combining FFA and
microsphere for localized drug delivery may enable cost-effective, extended
release local delivery to the inner ear of new and existing small molecules,
proteins, peptides, and nucleic acids.
PMID- 29329747
TI - Antibacterial properties of Latarcin 1 derived cell-penetrating peptides.
AB - Cell-penetrating peptides (CPPs) and antimicrobial peptides (AMPs) share certain
physicochemical parameters such as amphipathicity, hydrophobicity, cationicity
and pI, due to which these two groups of peptides also exhibit overlapping
functional characteristics. In our current work, we have evaluated antimicrobial
properties of cell-penetrating peptides derived from Latarcin1. Latarcin derived
peptide (LDP) exhibited antimicrobial activity against representative
microorganisms tested and bactericidal effect against methicillin resistant
Staphylococcus aureus (MRSA), which was used as model organism of study in the
present work. However, LDP exhibited cytotoxicity against HeLa cells. Further,
nuclear localization sequence (NLS) was fused to LDP and interestingly, LDP-NLS
showed antimicrobial effect against bacteria, showed bactericidal effect against
MRSA and also did not exhibit cytotoxicity in HeLa cells till the highest
concentrations tested. Thus, our results inferred that fusion of NLS to LDP
significantly reduced cytotoxicity of LDP against HeLa cells (Ponnappan and
Chugh, 2017) and exhibited significantly higher cell-penetrating activity in MRSA
in comparison to LDP alone. Consolidated results of uptake assays, time-kill
assays and PI membrane damage assays show that LDP killed MRSA mainly by membrane
damage, where as LDP-NLS might have intracellular targets. Owing to its cell
penetrating activity in HeLa cells and antimicrobial activity against MRSA, LDP
NLS efficiently inhibited intracellular infection of MRSA in HeLa cells as
observed in invasion assays. Hence, our results suggest that LDP-NLS is a dual
action peptide with AMP and CPP activity and could be potential candidate as
peptide antibiotic and drug delivery vector in both mammalian and bacterial
cells.
PMID- 29329748
TI - Oral Bifidobacterium longum expressing GLP-2 improves nutrient assimilation and
nutritional homeostasis in mice.
AB - Bifidobacterium has been developed for the oral delivery of peptides and has the
added beneficial effect on our bodies through its probiotic properties. Here, we
utilize Bifidobacterium as a delivery system to orally deliver Glucagon like
peptide-2 (GLP-2). We constructed vector derived from pET-31b(+) to construct a
Bifidobacterium longum expressing GLP-2. We then determined the bioactivity of
recombinant Bifidobacterium in Caco-2 cells. Finally, we quantified newly
synthesized ApoB48 and chylomicron production in mice infused with exogenous GLP
2 or Bifidobacterium expressing GLP-2. Results based on secretion of the
triglyceride (TG)-rich lipoprotein (TRL)-ApoB48 and secretion of chylomicron
revealed that recombinant Bifidobacterium was efficient in treating intestinal
dysfunction,suggesting an alternative way to use Bifidobacterium as a delivery
system to deliver GLP-2 for gastrointestinal nutrition coordination.
PMID- 29329749
TI - Assessment of the diagnostic performance of four methods for the detection of
Giardia duodenalis in fecal samples from human, canine and feline carriers.
AB - Enteric parasitic diseases including giardiasis are of public health concern.
Different methods are available for the diagnosis of this parasitic infection in
fecal samples such as the identification of protozoan cysts and trophozoites by
light microscopy, detection of specific antigens by ELISA, and amplification of
DNA fragments by PCR. The present study aimed at assessing the performance of
four laboratory tests for the detection of Giardia duodenalis in fecal specimens
from three different host species with a previous diagnosis of giardiasis;
canine, feline and human patients provided new stool samples to be retested for
Giardia before initiating treatment with antiprotozoal drugs. For this purpose,
triplicate fecal specimens from 54 humans, 24 dogs and 18 cats living in the city
of Niteroi, RJ, southeast Brazil, were analysed by light microscopy, ELISA,
immunochromatography, and nested PCR. The centrifugal-flotation method detected
Giardia cysts in 89.6% (86/96) of the fecal samples. The protozoan parasite was
detected via immunochromatography in 87.5% (84/96) of these samples. Giardia was
detected by ELISA in 69.8% (67/96) of the stool specimens from carriers with a
previous diagnosis of Giardia infection. Giardia was detected by PCR in only
39.6% (38/96) of the fecal specimens. Based on these findings, we suggest that,
among the four assays that were used in this study, the zinc sulphate flotation
technique (Faust et al., 1939) is the best diagnostic assay in terms of
sensitivity and specificity to detect G. duodenalis on serially collected samples
from dogs, cats and humans.
PMID- 29329750
TI - Women and the Experience of Pain and Opioid Use Disorder: A Literature-based
Commentary.
AB - It is generally understood that pain experience and opioid abuse have relied on
male-dominated models. However, sex and gender play a role in both pain
experience and opioid use disorder. Using the previously validated Texas Tech
University Health Sciences Center Sex and Gender Specific Health PubMed Advanced
Search Tool, the authors used pertinent literature to develop this literature
based commentary on sex and gender differences in pain experience and opioid use
disorder. Women report their experience of pain more frequently, have increased
rates of diagnoses related to pain, have increased pain sensitivity, and have a
variable response to pain and analgesia. This variable response is due to
anatomic, physiologic, hormonal, psychological, and social factors that differ by
sex and gender. Women have been found to be at greater risk for opioid abuse in
all age groups. This may be due to the differences in pain experience, as well as
sex and gender differences in prescribing patterns, cultural norms, and the
increased likelihood to experience dependency and withdrawal. Approaches to the
treatment of opioid use disorder are also subject to sex and gender differences
an area in need of further investigation.
PMID- 29329751
TI - Progress in the neurosciences and the training of medical students.
PMID- 29329752
TI - Role of frozen section in sentinel lymph node biopsy for breast cancer in the era
of the ACOSOG Z0011 and IBCSG 23-10 trials.
AB - BACKGROUND: Intraoperative frozen sections (FS) of sentinel lymph nodes (SLN)
were evaluated to avoid the need for deferred axillary lymph node dissection
(ALND) in patients with early breast cancer (EBC). However, FS has low
sensitivity for detecting micro-metastases (<2 mm), resulting in patients who
later undergo deferred ALND. The aim of the study was to determine the best
clinical approach for selecting patients who would derive real benefit from ALND,
as well as to minimize the functional and psychological damage caused by delayed
surgery, and the risk of undertreating EBC patients. METHODS: This study
evaluated 1453 patients with early breast cancer (EBC) who underwent SLN biopsy,
FS and definitive evaluation. Causes of discrepancies between SLN biopsy and FS
results and the need for further surgery were evaluated. RESULTS: A total of 1226
(86%) patients underwent FS; of these patients, 146 (11.9%) were false negatives.
The global sensitivity of FS in detecting both macro and micrometastases was
53.7%. Although ACOSOG Z0011 criteria found that ALND could be avoided in 236
patients, 40 (17%) of these had >3 positive axillary lymph nodes. In contrast,
application of the IBCSG 23-10 trial criteria, found that only three patients
(3.1%) had >3 positive axillary lymph nodes. CONCLUSIONS: FS has a low
sensitivity in detecting micrometastases (19%), but a reasonable sensitivity for
macrometastases (75%). Most false negatives were smaller metastases (mean 2.1 mm)
and more likely in patients with infiltrating lobular carcinoma. Retrospective
modelling of the IBCSG 23-10 criteria reduced the percentage of patients
requiring deferred surgery from 12% to 4%. Guidelines recommend irradiation of
lymph node drainage stations in patients with >=4 axillary metastatic lymph
nodes. Omission of ALND from 40% of patients who met Z0011 criteria would have
resulted in their undertreatment. This risk decreases to 3% by omitting axillary
clearing only in patients with micrometastases.
PMID- 29329753
TI - Does social context matter? An ecological momentary assessment study of marijuana
use among college students.
AB - INTRODUCTION: Past research has shown that marijuana use occurs commonly in
social situations for young adults, though few studies have examined the
association between immediate social context and marijuana use patterns and
associated problems. The current study examined the impact of demographics,
marijuana use and problem use, alcohol use, craving, and social context on the
likelihood of using marijuana with others via ecological momentary assessment
(EMA). METHODS: College-student marijuana users (N=56) were recruited and
completed a baseline assessment and training on the two-week signal-contingent
EMA protocol. Participants were sent text messages three times per day randomly
for two weeks. RESULTS: Of the 1131 EMA instances during which participants
reported using marijuana, 862 (76.22%) were labeled as being with others. Forty
five participants (80.36%) reported marijuana use with others present during at
least half of the times they used marijuana. Findings from a multilevel logistic
regression model showed a significant positive association between the
probability of using with others and minutes spent using marijuana (b=0.047,
p<0.001), social facilitation (b=0.138, p<0.001), and DSM-IV diagnosis
(dependence versus no diagnosis, b=1.350, p=0.047). CONCLUSIONS: Cannabis
dependence, more time using marijuana in the moment, and using for social
facilitation purposes were positively associated with using marijuana in the
context of being with others. Daily users had more variability in terms of the
social context of their use. This study illustrates the complex relationship
between social context and marijuana use.
PMID- 29329754
TI - Comparison of Cepheid(r) Xpert Flu and Roche RealTime Ready Influenza A/H1N1
Detection Set for detection of influenza A/H1N1.
AB - OBJECTIVE: To compare two influenza polymerase chain reaction (PCR) methods.
METHODS: A total of 749 suspected MERS-CoV patients presenting at Johns Hopkins
Aramco Healthcare, Saudi Arabia, each submitted a clinical sample for influenza A
reflex testing using the on-site Cepheid(r) Xpert Flu assay and at the Ministry
of Health laboratory by the Roche PCR assay. RESULTS: There was 92.12% overall
agreement between the two methods. Specificity of the Cepheid(r) Xpert Flu was
95.8% for H1N1 and 94.4% for total influenza A. Cepheid(r) Xpert Flu sensitivity
for influenza A was 100% for younger patients (0-19-year age group) but
significantly lower both for older patients (68.2% for 60-79-year and 50% for
>=80-year age groups) and overall for males compared to females (72.6% and 94.0%,
respectively). CONCLUSIONS: Specificity of the Cepheid(r) Xpert Flu test was
high; however, sensitivity for total influenza A was lower particularly in males
and older patients.
PMID- 29329755
TI - Detection of "Xisco" gene for identification of Streptococcus pneumoniae
isolates.
AB - We describe a PCR-assay differentiating Streptococcus pneumoniae from closely
related species of the Mitis group of the genus Streptococcus and identification
of pneumococcus clinical isolates, based on the "Xisco" gene discriminatory
marker. The complete "Xisco" gene sequence was observed in all S. pneumoniae
genomes analyzed and absent in all non-pneumococcus genomes.
PMID- 29329756
TI - Phospholipid composition of the outer membrane of Escherichia coli influences its
susceptibility against antimicrobial peptide apidaecin 1b.
AB - Proline-rich antimicrobial peptides (PrAMPs) kill bacteria in a multimodal
mechanism by inhibiting the 70S ribosome (i.e., protein translation) as dominant
lethal mechanism besides inhibition of several other proteins, such as chaperone
DnaK. PrAMPs pass the outer membrane of Gram-negative bacteria, probably by a
self-promoted uptake followed by a transporter-mediated uptake from the
periplasm. Mutation of transporter protein SbmA is a well-studied resistance
mechanism observed in vitro by resistance induction with PrAMPs. Here, we
compared the membrane compositions of Escherichia coli BL21AI and BL21AI Apir,
which was obtained by resistance induction with PrAMP apidaecin 1b. Lipid A was
partially modified by phosphatidylethanolamine, 4-aminoarabinose, or both groups,
but the relative contents of these and further unidentified species did not
differ much between wild-type and resistant strains, indicating that resistance
was not related to lipid A modifications. The same was true for 20
glycerophospholipids identified, i.e., 11 phosphatidylethanolamines and 9
phosphatidylglycerols. However, glycerophospholipids in BL21AI Apir contained
much lower levels of cyclopropane-modified acyl groups, which probably alter the
biophysical properties of the inner membrane and the inner leaflet of the outer
membrane. Indeed, when cyclopropane-fatty-acyl-phospholipid synthase was knocked
out in E. coli BW25113, the resulting BW25113 Deltacfa was less susceptible
against apidaecin 1b.
PMID- 29329758
TI - Real-time RT-PCR, a necessary tool to support the diagnosis and surveillance of
rotavirus in Mexico.
AB - Rotavirus produces diarrhea in children under 5 years old. Most of those
conventional methods such as polyacrylamide gel electrophoresis (PAGE) and
reverse transcription-polymerase chain reaction (RT-PCR) have been used for
rotavirus detection. However, these techniques need a multi-step process to get
the results. In comparison with conventional methods, the real-time RT-PCR is a
highly sensitive method, which allows getting the results in only one day. In
this study a real-time RT-PCR assay was tested using a panel of 440 samples from
patients with acute gastroenteritis, and characterized by PAGE and RT-PCR. The
results show that the real-time RT-PCR detected rotavirus from 73% of rotavirus
negative samples analyzed by PAGE and RT-PCR; thus, the percentage of rotavirus
positive samples increased to 81%. The results indicate that this real-time RT
PCR should be part of a routine analysis, and as a support of the diagnosis of
rotavirus in Mexico.
PMID- 29329759
TI - Treatment outcomes of macrolide-susceptible Mycobacterium abscessus lung disease.
AB - Mycobacterium abscessus lung disease is difficult to treat due to inducible
resistance to macrolides. However, 15%-20% of isolates are macrolide susceptible.
In 14 patients with macrolide-susceptible M. abscessus lung disease, all isolates
had nonfunctional erm(41) gene, and sputum culture conversion rate was achieved
in 93% (13/14) following antibiotic therapy.
PMID- 29329757
TI - Challenges of Francisella classification exemplified by an atypical clinical
isolate.
AB - The accumulation of sequenced Francisella strains has made it increasingly
apparent that the 16S rRNA gene alone is not enough to stratify the Francisella
genus into precise and clinically useful classifications. Continued whole-genome
sequencing of isolates will provide a larger base of knowledge for targeted
approaches with broad applicability. Additionally, examination of genomic
information on a case-by-case basis will help resolve outstanding questions
regarding strain stratification. We report the complete genome sequence of a
clinical isolate, designated here as F. novicida-like strain TCH2015, acquired
from the lymph node of a 6-year-old male. Two features were atypical for F.
novicida: exhibition of functional oxidase activity and additional gene content,
including proposed virulence determinants. These differences, which could
potentially impact virulence and clinical diagnosis, emphasize the need for more
comprehensive methods to profile Francisella isolates. This study highlights the
value of whole-genome sequencing, which will lead to a more robust database of
environmental and clinical genomes and inform strategies to improve detection and
classification of Francisella strains.
PMID- 29329760
TI - Sodium-glucose transporter as a novel therapeutic target in disease.
AB - Glucose is the primary energy fuel of life. A glucose transporter, the sodium
glucose transporter (SGLT), is receiving attention as a novel therapeutic target
in disease. This review summarizes the physiological role of SGLT in cerebral
ischemia, cancer, cardiac disease, and intestinal ischemia, which has encouraged
analysis of SGLT function. In cerebral ischemia and cardiomyopathy, SGLT-1 is
involved in worsening of the injury. In addition, SGLT-1 promotes the development
of cancer. On the other hand, SGLT-1 has a protective effect against cardiac and
intestinal ischemia. Interestingly, SGLT-1 expression levels are increased in
some diseased tissue, such as in cerebral ischemia and cancer. This suggests that
SGLT-1 may have an important role in many diseases. This review discusses the
potential of SGLT as a target for novel therapeutic agents.
PMID- 29329761
TI - N-terminal pro-B-type natriuretic peptide for monitoring after balloon pulmonary
angioplasty for chronic thromboembolic pulmonary hypertension.
AB - BACKGROUND: Balloon pulmonary angioplasty (BPA) is an emerging interventional
treatment option for chronic thromboembolic pulmonary hypertension (CTEPH). The
non-invasive monitoring of CTEPH patients is a clinical challenge. In this study
we examined changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) in
patients undergoing BPA for inoperable CTEPH and related them to peri-procedural
success. METHODS: In this study we analyzed a total of 51 consecutive patients
who underwent BPA treatment and completed a 6-month follow-up (6-MFU) between
March 2014 and March 2017. Serum samples for NT-proBNP measurement were collected
before every BPA and at 6-MFU. RESULTS: The 51 patients underwent 265
interventions involving angioplasty of a total of 410 vessels. The 6-month
survival rate was 96.1%. The baseline (BL) mean pulmonary artery pressure (PAP)
was 39.5 +/- 12.1 mm Hg, pulmonary vascular resistance (PVR) was 515.8 +/- 219.2
dynes/s/cm5 and the median NT-proBNP level was 820 (153 to 1,871.5) ng/liter. At
BL, World Health Organization functional class (FC) was >=III in 96.1% of the
patients, whereas, at 6-MFU, 11.8% were in WHO FC >=III. At 6-MFU, mean PAP (32.6
+/- 12.6 mm Hg; p < 0.001), PVR (396.9 +/- 182.6 dynes/s/cm5; p < 0.001) and NT
proBNP (159.3 [84.4 to 464.3] ng/liter; p < 0.001) levels were reduced. The
decrease in NT-proBNP levels correlated with the decrease in mean PAP (rrs =
0.43, p = 0.002) and PVR (rrs = 0.50, p = 0.001). A reduction in the NT-proBNP
level of 46% indicated a decrease in mean PAP of >=25% (area under the curve
[AUC] = 0.71) and a reduction of 61% indicated a decrease in PVR of >=35% (AUC
0.77). CONCLUSIONS: Our results demonstrate that NT-proBNP levels decrease after
BPA, providing valuable evidence of procedural success. NT-proBNP measurement
allows identification of patients who are BPA non-responders and may thus be a
valuable adjunct in therapy monitoring.
PMID- 29329762
TI - Smoking and HIV: confronting the epidemic.
PMID- 29329764
TI - [Analysis of mortality and hospital stay in cardiac surgery in Mexico 2015: Data
from the National Cardiology Institute].
AB - OBJECTIVE: To analyse hospital mortality in patients subjected to cardiac surgery
in Mexico during the year 2015, and identify the mortality risks factors, and its
correlation with days of hospital stay in the cardiovascular intensive care unit.
METHOD: The database of Cardiovascular Intensive Care of the National Institute
of Cardiology was examined for this cases and controls study that included only
adult patients subjected to cardiac surgery during the year 2015. RESULTS: A
total of 571 patients were subjected to a surgical procedure. The predominant
indication was single or multiple valve replacement surgery, followed by coronary
revascularisation surgery, and correction of adult congenital heart disease.
Overall mortality was 9.2, and 8% died in intensive care. The main risk factors
for death were preoperative organ failure or pulmonary hypertension, and
prolonged time with extracorporeal circulation. The primary cause of death was
secondary to cardiogenic shock. The hospital mortality observed in this
population was higher for patients undergoing pulmonary thromboendarterectomy,
complex aortic disease surgery, and valvular surgery. CONCLUSIONS: The mortality
of patients undergoing cardiac surgery in Mexico differs slightly from that
reported in the world literature, primarily because there were more multivalvular
surgeries and mixed complex procedures performed.
PMID- 29329765
TI - Usefulness of the Trabecular Bone Score for assessing the risk of osteoporotic
fracture.
AB - INTRODUCTION AND OBJECTIVES: The trabecular bone score (TBS) is an imaging
technique that assesses the condition of the trabecular microarchitecture.
Preliminary results suggest that TBS, along with the bone mineral density
assessment, could improve the calculation of the osteoporotic fracture risk. The
aim of this study was to analyse TBS values and their relationship with the
clinical characteristics, bone mineral density and history of fractures of a
cohort of posmenopausal women. MATERIAL AND METHODS: We analysed 2,257
posmenopausal women from the FRODOS cohort, which was created to determine the
risk factors for osteoporotic fracture through a clinical survey and bone
densitometry with vertebral morphometry. TBS was applied to the densitometry
images. TBS values <=1230 were considered indicative of degraded
microarchitecture. We performed a simple and multiple linear regression to
determine the factors associated with this index. RESULTS: The mean TBS value in
L1-L4 was 1.203+/-0.121. Some 55.3% of the women showed values indicating
degraded microarchitecture. In the multiple linear regression analysis, the
factors associated with low TBS values were age, weight, height, spinal T-score,
glucocorticoid treatment, presence of type 2 diabetes and a history of fractures
due to frailty. CONCLUSIONS: TBS showed microarchitecture degradation values in
the participants of the FRODOS cohort and was associated with anthropometric
factors, low bone mineral density values, the presence of fractures, a history of
type 2 diabetes mellitus and the use of glucocorticoids.
PMID- 29329766
TI - 77-year-old woman with pulse abnormalities.
PMID- 29329763
TI - Efficacy and safety of varenicline for smoking cessation in people living with
HIV in France (ANRS 144 Inter-ACTIV): a randomised controlled phase 3 clinical
trial.
AB - BACKGROUND: Tobacco smoking is common in people living with HIV, but high-quality
evidence on interventions for smoking cessation is not available in this
population. We aimed to assess the efficacy and safety of varenicline with
counselling to aid smoking cessation in people living with HIV. METHODS: The ANRS
144 Inter-ACTIV randomised, parallel, double-blind, multicentre, placebo
controlled phase 3 trial was done at 30 clinical hospital sites in France. People
living with HIV who had smoked at least ten cigarettes per day for 1 year or
longer, were motivated to stop smoking, were not dependent on another
psychoactive substance, and had no history of depression or suicide attempt were
eligible. Using a computer-generated randomisation sequence, we allocated (1:1)
the patients to receive either varenicline titrated to two 0.5 mg doses twice
daily or placebo twice daily for 12 weeks, plus face-to-face counselling.
Patients and investigators were masked to treatment group allocation. Patients
who were not abstinent at week 24 were offered open-label varenicline for 12
additional weeks. The primary outcome was the proportion of smokers continuously
abstinent from week 9 to week 48. Smoking status was confirmed by carbon monoxide
in exhaled air. Primary analyses were done in both the intention-to-treat (ITT)
population and modified ITT (mITT) population, which comprised all patients who
took at least one tablet of their assigned study treatment. The safety analyses
were done in the mITT population. The trial is registered at ClinicalTrials.gov,
number NCT00918307. The trial status is complete. FINDINGS: From Oct 26, 2009, to
Dec 20, 2012, of 303 patients assessed for eligibility, 248 patients were
randomly assigned to the varenicline group (n=123) or the placebo group (n=125).
After randomisation, one participant initially assigned to the placebo group was
excluded from the ITT analysis for a regulatory reason (no French health-care
coverage). 102 patients in the varenicline group and 111 patients in the placebo
group received at least one dose of their assigned treatment and were included in
the mITT analysis. In the ITT analysis, varenicline was associated with a higher
proportion of patients achieving continuous abstinence over the study period
(week 9-48): 18 (15%, 95% CI 8-21) of 123 in the varenicline group versus eight
(6%, 2-11) of 124 in the placebo group, adjusted odds ratio (OR) 2.5 (95% CI 1.0
6.1; p=0.041). In the mITT analysis, varenicline was also associated with higher
continuous abstinence: 18 (18%, 95% CI 10-25) of 102 versus eight (7%, 2-12) of
111 in the placebo group (adjusted OR 2.7, 95% CI 1.1-6.5; p=0.029). The
incidence of depression was 2.4 per 100 person-years (95% CI 0.6-9.5; two [2%] of
102) in the varenicline group and 12.4 per 100 person-years (95% CI 6.9-22.5; 11
[10%] of 111) in the placebo group. 14 (7%) of 213 participants had 18
cardiovascular events: six (6%) of 102 people in the varenicline group and eight
(7%) of 111 people in the placebo group. INTERPRETATION: Varenicline is safe and
efficacious for smoking cessation in people living with HIV and should be
recommended as the standard of care. FUNDING: The French National Institute for
Health and Medical Research (INSERM)-French National Agency for Research on AIDS
and Viral Hepatitis (ANRS) and Pfizer.
PMID- 29329767
TI - Discussion.
PMID- 29329768
TI - Management of pediatric ovarian torsion: evidence of follicular development after
ovarian preservation.
AB - PURPOSE: This study reviews contemporary management and follow-up of pediatric
ovarian torsion. METHODS: This is a retrospective series of patients from birth
to 19 years undergoing operative management of ovarian torsion from 2012 to 2016.
RESULTS: We studied 43 girls who underwent 51 operations for ovarian torsion. The
median age was 8.3 years. Ultrasound was utilized for diagnosis in 24/29 patients
(83%) evaluated in a children's hospital. In contrast, computed tomography was
used initially in 7 cases (50%) in children imaged at non-children's hospitals
before transfer. Initial operation for ovarian torsion was completed
laparoscopically in 38 (88%). Overall, ovarian preservation was performed in 37
(86%) patients, while 6 (13%) underwent oophorectomy. Indications for
oophorectomy included 5 infants with in utero torsion and an 18-year-old with a
suspected malignancy. In girls with acute ovarian torsion, the oophorectomy rate
was reduced to 2%. Postoperatively, 1 patient developed a small bowel obstruction
requiring operation after laparoscopic ovarian detorsion. Recurrent torsion
occurred in 3 patients (7%). In total, 34 patients underwent postoperative
ovarian imaging. A total of 25 (74%) had follicles visualized in the previously
torsed ovary. CONCLUSION: Ovarian-sparing operations for acute torsion are safe
and result in ovarian salvage and preservation of follicular development in more
than 70% of children and adolescents.
PMID- 29329769
TI - Erratum to "Absorption, liver first-pass effect, pharmacokinetics and tissue
distribution of calycosin-7-O-beta-d-glucopyranoside (C7G) and its major active
metabolite, calycosin, following oral administration of C7G in rats by LC-MS/MS"
[J. Pharm. Biomed. Anal. 148 (2018) 350-354].
PMID- 29329770
TI - Yield of family screening in patients with isolated bicuspid aortic valve in a
general hospital.
AB - AIM: To determine the prevalence of unidentified bicuspid aortic valve (BAV) or
aortic dilatation (>40mm) in first degree relatives (FDR) of patients with
isolated BAV in a general hospital. METHODS AND RESULTS: Patients with isolated
BAV received information advising cardiac screening of their FDR. Referred and
screened were 134 FDR of 54 adult index patients with isolated BAV (median 2 per
index patient). FDR's mean age was 49years (range 16-83years) and 41% were male.
They comprised 5 parents (3.7%), 52 siblings (39%) and 77 offspring (57%). Among
these FDR, the prevalence of BAV was 6.0% (8 patients). In FDR without BAV, 10
(7.5%) had aortic dilatation. 'Familial BAV' was present in 9/54 families (17%).
CONCLUSION: In a general hospital, screening of FDR of patients with isolated BAV
resulted in a substantial yield of 13% new cases with BAV or aortic dilatation
without BAV.
PMID- 29329771
TI - Low rate of revascularization procedures and poor prognosis particularly in male
patients with peripheral artery disease - A propensity score matched analysis.
AB - BACKGROUND: Few data discuss the impact of sex on diagnostic and therapeutic
procedures and outcome of patients with peripheral artery disease (PAD). METHODS:
We obtained data on 41,873 PAD patients between 2009 and 2011 (including a 4-year
follow-up) from the largest German public health insurance (BARMER GEK).
Propensity Score Matching (PSM) was performed to evaluate the impact of sex on
treatment, complications, in-hospital and long-term outcome. RESULTS: Of 41,873
PAD patients, there were 23,282 (55.6%) male and 18,591 (44.4%) female. Male
patients were younger (69+/-11years vs. 75+/-12years in females; p<0.001) but had
higher obesity (8.0% vs 6.5%), dyslipidemia (33.2% vs 28.1%), smoking (12.9% vs
9.2%), coronary artery disease (29.4% vs 19.5%), or diabetes rates (35.8% vs
28.1%; each p<0.001). Almost three in five revascularizations applied to minor
clinical stages, revascularization rate in critical limb ischemia (CLI) was 49%
at in-hospital and 58.8% inc. follow-up in both sexes (Rutherford 6). PSM
accounting for risk factors and PAD stages showed lower use of endovascular and
higher use of surgical revascularization in males compared to females. Male sex
was associated with higher in-hospital amputation and was an independent risk
factor during follow-up for both amputation (HR 1.284; p<0.001) and death (HR
1.155; p<0.001). CONCLUSIONS: Data show low rates of revascularization procedures
particularly at advanced PAD stages (CLI). Male sex is associated with higher use
of surgical, but lower use of endovascular and overall procedures, and higher
amputation and mortality during follow-up.
PMID- 29329772
TI - Robust decentralized controller for minimizing coupling effect in single inductor
multiple output DC-DC converter operating in continuous conduction mode.
AB - This paper describes a novel robust decentralized control design methodology for
a single inductor multiple output (SIMO) DC-DC converter. Based on a nominal
multiple input multiple output (MIMO) plant model and performance requirements, a
pairing input-output analysis is performed to select the suitable input to
control each output aiming to attenuate the loop coupling. Thus, the plant
uncertainty limits are selected and expressed in interval form with parameter
values of the plant model. A single inductor dual output (SIDO) DC-DC buck
converter board is developed for experimental tests. The experimental results
show that the proposed methodology can maintain a desirable performance even in
the presence of parametric uncertainties. Furthermore, the performance indexes
calculated from experimental data show that the proposed methodology outperforms
classical MIMO control techniques.
PMID- 29329774
TI - Enzymatic saccharification of lignocellulosic biorefinery: Research focuses.
AB - To realize lignocellulosic biorefinery is of global interest, with enzymatic
saccharification presenting an essential stage to convert polymeric sugars to
mono-sugars for fermentation use. This mini-review summarizes qualitatively the
research focuses discussed the review articles presented in the past 22 months
and other relevant papers. The research focuses on pretreatment with improved
efficiency, enhanced enzyme production with high yields and high extreme
tolerance, feasible combined saccharification and fermentation processes,
detailed mechanisms corresponding to the enzymatic saccharification in
lignocellulosic biorefinery, and the costs are discussed.
PMID- 29329773
TI - Total energy expenditure and body composition of children with developmental
disabilities.
AB - BACKGROUND: Obesity prevalence is increased in children with developmental
disabilities, specifically in children with spina bifida and Down syndrome.
Energy expenditure, a critical aspect of weight management, has been extensively
studied in the typically developing population, but not adequately studied in
children with developmental disabilities. OBJECTIVE: Determine energy
expenditure, fat-free mass and body fat percentile and the impact of these
findings on recommended caloric intake in children with spina bifida and Down
syndrome. METHODS/MEASURES: This pilot study included 36 children, 18 with spina
bifida, 9 with Down syndrome and 9 typically developing children. Half of the
children with spina bifida were non-ambulatory. Doubly labeled water was used to
measure energy expenditure and body composition. Descriptive statistics described
the sample and MANOVA and ANOVA methods were used to evaluate differences between
groups. RESULTS: Energy expenditure was significantly less for children with
spina bifida who primarily used a wheelchair (p = .001) and children with Down
syndrome (p = .041) when compared to children without a disability when adjusted
for fat-free mass. However, no significant difference was detected in children
with spina bifida who ambulated without assistance (p = .072). CONCLUSIONS:
Children with spina bifida and Down syndrome have a significantly decreased
energy expenditure which directly impacts recommended caloric intake. No
significant difference was detected for children with spina bifida who ambulated,
although the small sample size of this pilot study may have limited these
findings. Validating these results in a larger study is integral to supporting
successful weight management of these children.
PMID- 29329775
TI - Recent advances and strategies in process and strain engineering for the
production of butyric acid by microbial fermentation.
AB - Butyric acid is an important platform chemical, which is widely used in the
fields of food, pharmaceutical, energy, etc. Microbial fermentation as an
alternative approach for butyric acid production is attracting great attention as
it is an environmentally friendly bioprocessing. However, traditional
fermentative butyric acid production is still not economically competitive
compared to chemical synthesis route, due to the low titer, low productivity, and
high production cost. Therefore, reduction of butyric acid production cost by
utilization of alternative inexpensive feedstock, and improvement of butyric acid
production and productivity has become an important target. Recently, several
advanced strategies have been developed for enhanced butyric acid production,
including bioprocess techniques and metabolic engineering methods. This review
provides an overview of advances and strategies in process and strain engineering
for butyric acid production by microbial fermentation. Additionally, future
perspectives on improvement of butyric acid production are also proposed.
PMID- 29329776
TI - Sequential dark and photo fermentation hydrogen production from hydrolyzed corn
stover: A pilot test using 11 m3 reactor.
AB - Pilot tests of sequential dark and photo fermentation H2 production were for the
first time conducted in a 11 m3 reactor (3 m3 for dark and 8 m3 for photo
compartments). A combined solar and light-emitting diode illumination system and
a thermal controlling system was installed and tested. With dark fermentation
unit maintained at pH 4.5 and 35 degrees C and photo fermentation unit at pH 7.0
and 30 degrees C, the overall biogas production rate using hydrolyzed corn
stover as substrate reached 87.8 +/- 3.8 m3/d with 68% H2 content, contributed by
dark unit at 7.5 m3-H2/m3-d and by photo unit at 4.7 m3/m3-d. Large variation was
noted for H2 production rate in different compartments of the tested units,
revealing the adverse effects of poor mixing, washout, and other inhomogeneity
associated with large reactor operations.
PMID- 29329777
TI - Dietary intake by food group of individuals with type 2 diabetes mellitus: A
systematic review.
AB - AIMS: To synthesize peer-reviewed literature that investigates the dietary intake
by food group of individuals with type 2 diabetes mellitus (T2DM) and compare
intakes to national and international dietary guidelines. METHODS: Four
electronic databases (MEDLINE, EMBASE, CINAHL and Web of Sciences) were searched
for studies that investigated the dietary intake of adults (>=18 years) with T2DM
using the five main food groups (fruit, vegetables, dairy, grains and meat/meat
alternatives). Food group intake in serves was compared against national
guidelines and fruit and vegetable intake in grams was compared against the World
Health Organization (WHO) guidelines. RESULTS: After screening 13,662
publications, 11 studies were included. All reported cross-sectional data.
Majority of participants were consuming less than the recommended serves of
fruit, vegetables, grains and dairy and were meeting or exceeding the recommended
serves for meat/meat alternatives. Two of six studies reported fruit and
vegetable recommendations were being met, two reported dairy recommendations were
being met and two reported grain recommendations were being met. Of the five
studies reporting intake in grams, four met the WHO minimum intake for fruit and
vegetables. CONCLUSIONS: Individuals with T2DM do not comply with food group
recommendations; particularly for fruit, vegetables, dairy and grains.
Longitudinal research is required to better understand how food group intake
changes over time after diagnosis.
PMID- 29329778
TI - High-intensity interval training versus continuous training on physiological and
metabolic variables in prediabetes and type 2 diabetes: A meta-analysis.
AB - AIMS: To compare the effects of high-intensity interval training (HIIT) versus
moderate-intensity continuous training (MICT) on functional capacity and
cardiometabolic markers in individuals prediabetes and type 2 diabetes (T2D).
METHODS: The search was performed in PubMed (MEDLINE), EMBASE, PEDro, CENTRAL,
Scopus, LILACS database, and Clinical Trials from the inception to July 2017,
included randomized clinical trials that compared the use of HIIT and MICT in
prediabetes and T2D adults. The risk of bias was defined by Cochrane Handbook and
quality of evidence by GRADE. RESULTS: From 818 relevant records, seven studies
were included in systematic review (64 prediabetes and 120 T2D patients) and five
with T2D were meta-analyzed. HIIT promoted significantly increased of 3.02
mL/kg/min (CI95% 1.42-4.61) of VO2max, measured for functional capacity, compared
to MICT. No differences were found between two modalities of exercises
considering the outcomes HbA1c, systolic and diastolic blood pressure, total
cholesterol, HDL and LDL cholesterol, triglycerides, BMI, and waist-to-hip ratio.
Most of the studies presented unclear risk of bias, and low and very low quality
of evidence. CONCLUSION: HIIT induces cardiometabolic adaptations similar to
those of MICT in prediabetes and T2D, and provides greater benefits to functional
capacity in patients with T2D. PROSPERO: CRD42016047151.
PMID- 29329779
TI - Receptor- and cellular compartment-specific activation of the cAMP/PKA pathway by
alpha1-adrenergic and ETA endothelin receptors.
AB - The signalling functions of many G protein-coupled receptors (GPCRs) expressed in
the myocardium are incompletely understood. Among these are the endothelin
receptor (ETR) family and alpha1-adrenergic receptor (alpha1-AR), which are
thought to couple to the G protein Galphaq. In this study, we used transcriptome
analysis to compare the signalling networks downstream of these receptors in
primary neonatal rat cardiomyocytes. This analysis indicated increased expression
of target genes of cAMP responsive element modulator (CREM) after 24 h treatment
with the alpha1-AR agonist phenylephrine, but not the ETR agonist endothelin-1,
suggesting a specific role for the alpha1-AR in promoting cAMP production in
cardiomyocytes. To validate the difference observed between these two GPCRs, we
used heterologous expression of the receptors and genetically encoded biosensors
in HEK 293 cell lines. We validated that both alpha1A- and alpha1B-AR subtypes
were able to lead to the accumulation of cAMP in response to phenylephrine in
both the nucleus and cytoplasm in a Galphas-dependent manner. However, the ETR
subtype ETA did not affect cAMP levels in either compartment. All three receptors
were coupled to Galphaq signalling as expected. Further, we showed that
activation of PKA in different compartments was alpha1-AR subtype specific, with
alpha1B-AR able to activate PKA in the cytoplasm and nucleus and alpha1A-AR only
able to in the nucleus. We provide evidence for a pathway downstream of the
alpha1-AR, and show that distinct pools of a receptor lead to differential
activation of downstream effector proteins dependent on their cellular
compartment.
PMID- 29329780
TI - Oncogenic RAC1 and NRAS drive resistance to endoplasmic reticulum stress through
MEK/ERK signalling.
AB - Cancer cells are able to survive under conditions that cause endoplasmic
reticulum stress (ER-stress), and can adapt to this stress by upregulating cell
survival signalling pathways and down-regulating apoptotic pathways. The cellular
response to ER-stress is controlled by the unfolded protein response (UPR). Small
Rho family GTPases are linked to many cell responses including cell growth and
apoptosis. In this study, we investigate the function of small GTPases in cell
survival under ER-stress. Using siRNA screening we identify that RAC1 promotes
cell survival under ER-stress in cells with an oncogenic N92I RAC1 mutation. We
uncover a novel connection between the UPR and N92I RAC1, whereby RAC1 attenuates
phosphorylation of EIF2S1 under ER-stress and drives over-expression of ATF4 in
basal conditions. Interestingly, the UPR connection does not drive resistance to
ER-stress, as knockdown of ATF4 did not affect this. We further investigate
cancer-associated kinase signalling pathways and show that RAC1 knockdown reduces
the activity of AKT and ERK, and using a panel of clinically important kinase
inhibitors, we uncover a role for MEK/ERK, but not AKT, in cell viability under
ER-stress. A known major activator of ERK phosphorylation in cancer is oncogenic
NRAS and we show that knockdown of NRAS in cells, which bear a Q61 NRAS mutation,
sensitises to ER-stress. These findings highlight a novel mechanism for
resistance to ER-stress through oncogenic activation of MEK/ERK signalling by
small GTPases.
PMID- 29329781
TI - Dopamine transporter trafficking is regulated by neutral sphingomyelinase
2/ceramide kinase.
AB - Dopamine (DA) reuptake is the primary mechanism to terminate dopaminergic
transmission in the synaptic cleft. The dopamine transporter (DAT) has an
important role in the regulation of DA reuptake. This study provides anatomical
and physiological evidence that DAT recycling is regulated by ceramide kinase via
the sphingomyelin pathway. First, the results show that DAT and neutral
sphingomyelinase 2 (nSMase2) were successfully co-precipitated from striatal
samples and were colocalized in the mouse striatum or PC12 cells. We also
identified a protein-protein interaction between nSMase2 and DAT through in situ
proximity ligation assay experiments in the mouse striatum. Second, dopamine (DA)
stimulated the formation of ceramide and increased nSMase activity in PC12 cells,
while treatment with a cell-permeable ceramide-1-phosphate (C1P) increased DA
uptake. Third, we used inhibitors and siRNA to inhibit nSMase2 and ceramide
kinase and observed the effects on DAT recycling in PC12 cells. Treatment with
ceramide kinase inhibitor K1, or nSMase inhibitor GW4869, decreased DA uptake in
PC12 cells, although the application of FB1, a ceramide synthase inhibitor, did
not affect DA uptake. Transfection of nSMase2 and CERK siRNA decreased DAT
surface level in PC12 cells. These results suggested that SM-derived C1P affects
cell surface levels of DAT.
PMID- 29329782
TI - LPA-induced migration of ovarian cancer cells requires activation of ERM proteins
via LPA1 and LPA2.
AB - Lysophosphatidic acid (LPA) has been implicated in the pathology of human ovarian
cancer. This phospholipid elicits a wide range of cancer cell responses, such as
proliferation, trans-differentiation, migration, and invasion, via various G
protein-coupled LPA receptors (LPARs). Here, we explored the cellular signaling
pathway via which LPA induces migration of ovarian cancer cells. LPA induced
robust phosphorylation of ezrin/radixin/moesin (ERM) proteins, which are membrane
cytoskeleton linkers, in the ovarian cancer cell line OVCAR-3. Among the LPAR
subtypes expressed in these cells, LPA1 and LPA2, but not LPA3, induced
phosphorylation of ERM proteins at their C-termini. This phosphorylation was
dependent on the Galpha12/13/RhoA pathway, but not on the Galphaq/Ca2+/PKC or
Galphas/adenylate cyclase/PKA pathway. The activated ERM proteins mediated
cytoskeletal reorganization and formation of membrane protrusions in OVCAR-3
cells. Importantly, LPA-induced migration of OVCAR-3 cells was completely
abolished not only by gene silencing of LPA1 or LPA2, but also by overexpression
of a dominant negative ezrin mutant (ezrin-T567A). Taken together, this study
demonstrates that the LPA1/LPA2/ERM pathway mediates LPA-induced migration of
ovarian cancer cells. These findings may provide a potential therapeutic target
to prevent metastatic progression of ovarian cancer.
PMID- 29329783
TI - Comparative genome based cis-elements analysis in the 5' upstream and 3'
downstream region of cell wall invertase and Phenylalanine ammonia lyase in
Nicotiana benthamiana.
AB - Plant secondary metabolites are widely used in human disease treatment; though
primary metabolism provides precursors for secondary metabolism, not much has
been studied to unravel the link connecting both the processes. Most common form
of gene regulation interconnecting diverse metabolism occurs at the
transcriptional and/or posttranscriptional level mediated by regulatory cis
elements. The present study aims at understanding the common cis-elements network
connecting the major primary metabolic enzyme, cell wall invertase (CWIN) and
secondary metabolism genes in Nicotiana benthamiana (N. benthamiana). The CWIN
and thirty one other gene sequences were extracted from N. benthamiana genome,
followed by cis-element analysis of their 5' upstream and 3' downstream region
using different programs (Genomatix software suite; PLACE and PlantCARe).
Comparative cis-element analysis of CWIN (N. benthamiana and other plant species)
and other primary, secondary metabolism and transcription factor genes (N.
benthamiana) revealed the occurrence of common stress associated cis-elements.
Predominantly, AHBP, L1BX, MYBL, MADS, MYBS, GTBX, DOFF and CCAF were found in
the 5' upstream region of all genes, whereas AHBP, MYBL, L1BX, HEAT, CCAF and
KAN1 were largely occurring in the 3' downstream region of all genes; indicating
common function of these elements in transcriptional and posttranscriptional gene
regulation. Further, genomic analysis using FGENESH, GenScan and homology based
methods (BlastX and BlastN) was performed on the N. benthamiana contigs harboring
CWIN and PAL, in an attempt to identify genomic neighborhood genes. The 5'
upstream and 3' downstream region of genes in the genomic neighborhood of CWIN
and PAL were also subjected to similar cis-element analysis, and the results
indicated cis-elements profile similar to CWIN, PAL and other primary, secondary
metabolism and transcription factor genes. The results of evolutionary studies
confirmed that the 5' upstream region of NbCWINs significantly showed more
proximity to secondary metabolism genes 4CL and the redox gene SOD, followed by
the phenylpropanoid pathway gene CHI. The 3' downstream regions of NbCWINs were
more closely related to other plant CWINs, followed by the redox gene, SOD and
primary metabolism gene FBA. Thus, the commonly found stress responsive cis
elements in our study can play a vital role in modulating key pathways of both
primary and secondary metabolism; thereby postulating their role in regulating
plant growth and metabolisms under unfavourable growth conditions.
PMID- 29329784
TI - Regulatory Science - An Underappreciated Component of Translational Research.
AB - Translational science refers to translating basic scientific findings to
practical application (i.e., 'bench-to-bedside'). An underappreciated aspect of
translational science is regulatory science. Herein, we focus on the importance
of regulatory science to facilitate development of innovative new drugs and
optimize use of approved drugs, with a call for community participation.
PMID- 29329785
TI - A relapsing fever group Borrelia sp. is widely distributed among wild deer in
Japan.
AB - A relapsing fever group Borrelia sp. was detected from the blood of wild deer
(Cervus nippon) in Japan. The Borrelia sp. was distributed nationwide among deer
with an overall prevalence of 26% in blood samples. The prevalence of infection
was significantly higher in fawns (48.4%) compared to adult deer (23.6%).
Sequencing analysis reveals that this Borrelia sp. belongs to the hard tick-borne
relapsing fever borreliae, and that it forms a single lineage based on sequences
of the flagellin and glycerophosphodiester phosphodiesterase genes. Borrelial
genome copy number was estimated at 8.8 * 103 genome copies/MUl of blood. Other
hard tick-borne relapsing fever borrelia (e.g. Borrelia miyamotoi) were not
detected in deer blood in this study. These findings suggest that wild deer may
act as reservoirs for this Borrelia sp. in Japan.
PMID- 29329786
TI - Clinicopathological and prognostic significance of lymphocyte to monocyte ratio
in patients with gastric cancer: A meta-analysis.
AB - BACKGROUND: Recently, the lymphocyte-to-monocyte ratio (LMR) has been reported to
be a prognostic factor in multiple malignancies. The current study was designed
to assess the prognostic value of pretreatment LMR in gastric cancer (GC).
METHODS: MEDLINE, EMBASE, Cochrane, and CNKI databases were searched until April
2017. Eligible articles were defined as studies assessing the prognostic role of
pretreatment LMR in GC. Pooled hazard ratios (HRs) for overall survival (OS),
disease-free survival (DFS), and recurrence-free survival (RFS) were calculated
using fixed-effects or random-effects models. RESULTS: A total of six studies
comprising 4908 patients were included in the study. Pooled results showed that
low LMR was significantly associated with decreased OS (HR: 0.66, 95% confidence
interval [CI]: 0.54-0.82, p < .001), but not with poor DFS/RFS (HR: 0.71, 95% CI:
0.38-1.32, p = .004). The unfavorable prognostic impact of low LMR on OS was
observed in patients of different disease stages and cut-off values. Moreover,
low LMR was significantly related to age (>median), gender (male), CEA (>5
ng/ml), tumor size (>3 cm), TNM stage (III-IV), lymph node metastasis, and
distant metastasis. CONCLUSIONS: Low pretreatment LMR may be a significant
prognostic biomarker for poor OS in patients with GC.
PMID- 29329787
TI - Outcomes of multisegmental transforaminal enlarged decompression plus posterior
pedicle screw fixation for multilevel lumbar spinal canal stenosis associated
with lumbar instability.
AB - PURPOSE: The aim of this study was to evaluate the clinical and radiologic
results of multisegmental transforaminal enlarged decompression (TED) plus
posterior pedicle screw fixation in the treatment of multilevel lumbar spinal
canal stenosis (LSCS) with lumbar instability (MLSCSI). METHODS: 113 patients
with MLSCSI underwent surgery were recruited in this study. All patients were
suffering from symptoms typical of degenerative LSCS and treated with either TED
plus fusion (TEDF group) or conventional laminectomy plus fusion (CLF group).
Clinical and radiologic parameters were evaluated. The clinical data, including
Visual Analog Scale (VAS) for back and leg pain, Oswestry Disability Index (ODI),
operative time, intraoperative blood loss, postoperative drainage, hospital stay,
and the rate of postoperative complications, were assessed. With respect to
radiologic parameters, mean disc height (MDH) and lumbar lordotic angle (LLA)
were measured using plain radiographs. Patient satisfaction was evaluated
according to the North American Spine Society (NASS) Outcome Questionnaire.
RESULTS: No serious complications occurred during the follow-up. The operative
time was significantly shorter for TEDF group than for CLF group, and similar
results were found with regard to the blood loss and postoperative drainage (p <
.05). The improvements in ODI, leg and back VAS scores were observed in both
groups after surgery and follow-up (P < .05). In the last follow-up, ODI and back
VAS scores in TEDF group were significantly higher than those in CLF group (P <
.05). Regarding radiologic variants, MDH and LLA were improved after operation
for 3 months (P > .05) and were all well maintained in the final follow-up in
both groups. Patients in TEDF group were more satisfied than patients in the CLF
group (85.2% vs 76.9%, p = .092). CONCLUSIONS: Satisfactory clinical and
radiological outcomes can be achieved with the use of multisegmental TED plus
lumbar fusion for the treatment of MLSCSI. This technique can reduce surgically
induced instability and obviously improve the symptoms and signs of the patients,
suggesting a safe and effective therapeutic procedure for MLSCSI.
PMID- 29329788
TI - Effect of individualized distal femoral valgus resection angle in primary total
knee arthroplasty: A systematic review and meta-analysis involving 1300 subjects.
AB - BACKGROUND: Proper limb alignment and implant positioning are important for
successful total knee arthroplasty (TKA). Whether any differences exist in
restoration of limb alignment for valgus knees between fixed and individual
femoral valgus correction angle (VCA) for distal femoral resection remains
unknown. METHODS: The PubMed, Medline, Embase, and Wangfang databases were
searched to identify studies comparing individualized VCA and fixed VCA in the
distal femoral valgus resection. The primary outcomes were the mechanical
femorotibial angle (MFT angle) and the proportion of postoperative alignment
deviation within +/-3 degrees . The secondary outcomes were femoral valgus
correction angle (VCA), component angle (alpha angle and beta angle). RESULTS:
Six studies with 1167 TKAs were analyzed quantitatively. The coronal limb
alignments in individualized group were closer to neutral than fixed group with a
mean 0.77 degrees difference (95% CI, -1.43 to -0.11; P = .022; I2 = 71.0%).
Moreover, there were more patients' postoperative alignment deviation within
neutral +/-3 degrees in the individualized group (RR, 1.23; 95% CI, 1.09 to
1.38; P = .00; I2 = 36.4%). The alpha angle were closer to neutral in the
individualized group, and there's 1.2 degrees more deviation from neutral in the
fixed group (95% CI, 0.99 to 1.41; P = .00; I2 = 0%). No difference was found in
the beta angle between groups (WMD, 0.85; 95% CI, -0.09 to 1.78; P = .075; I2 =
88.3%). CONCLUSIONS: This systematic review and meta-analysis demonstrated that
the individualized VCA for distal femoral resection could enhance the accuracy of
postoperative limb alignment and femoral component alignment in the coronal
plane. However, further high-quality RCTs and well-designed trials are still
needed.
PMID- 29329789
TI - Lateral lymph node metastasis in papillary thyroid carcinoma: A systematic review
and meta-analysis for prevalence, risk factors, and location.
AB - BACKGROUND: Lymph node metastasis (LNM) is frequent in papillary thyroid
carcinoma (PTC) and is associated with a poor prognosis. Unlike central LNM
(CLNM), there are few studies focusing on LLNM. We aimed to investigate the
prevalence and the risk factors for LLNM, with its most prevalent sites. METHODS:
We performed a comprehensive literature search using the PubMed and EMBASE
databases for relevant studies published prior to November 2016 that examined the
risk factors for LLNM. RESULTS: Twenty-three studies, including 18,741 patients,
were included. The prevalence of LLNM was 20.9% in all patients. CLNM (pooled OR
= 7.84, 95% CI = 6.13-10.02, p < .0001), extrathyroidal extension (pooled OR =
3.22, 95% CI = 2.21-4.70, p < .0001), tumor multifocality (pooled OR = 2.19, 95%
CI = 1.67-2.89, p < .0001), male sex (pooled OR = 1.72, 95% CI = 1.50-1.98, p <
.0001), upper pole location (pooled OR = 2.96, 95% CI = 1.93-4.53, p < .0001),
tumor size >=1.0 cm (pooled OR = 2.49, 95% CI = 1.71-3.61, p < .0001),
lymphovascular invasion (pooled OR = 3.96, 95% CI = 2.61-6.03, p < .0001) and
tumor bilaterality (pooled OR = 1.31, 95% CI = 1.12-1.53, p = .0006) were
significantly associated with LLNM. Most frequently affected areas were levels
III and IV. CONCLUSIONS: The prevalence of LLNM was high although the prognostic
impact is unknown. The significant risk factors for LLNM were not much different
from known risk factors for CLNM.
PMID- 29329790
TI - Plant-derived mPGES-1 inhibitors or suppressors: A new emerging trend in the
search for small molecules to combat inflammation.
AB - Inflammation comprises the reaction of the body to injury, in which a series of
changes of the terminal vascular bed, blood, and connective tissue tends to
eliminate the injurious agent and to repair the damaged tissue. It is a complex
process, which involves the release of diverse regulatory mediators. The current
anti-inflammatory agents are challenged by multiple side effects and thus, new
effective therapies are highly needed. The aim of this review is to summarize the
described microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors or
transcriptional suppressors from medicinal plants, which could be an ideal
approach in the management of inflammatory disorders, but need further clinical
trials in order to be ultimately validated.
PMID- 29329791
TI - Corrigendum to "Bcl xL deamidation and cancer: Charting the fame trajectories of
legitimate child and hidden siblings." [Biochim. Biophys. Acta 1864/10 (2017)
1734-1745].
PMID- 29329792
TI - [Implementation of a health promotion programme for women in social exclusion in
the city of Seville (Spain)].
AB - Health promotion can contribute towards reducing inequality and ensuring equal
opportunities, providing the means to enable the entire population to develop its
maximum health possibilities. Women living in areas with social transformation
needs (ASTN) are an especially vulnerable group due to the situation of material
deprivation and social exclusion in which they live. Health promotion programmes
for this group can bring about an improvement in their health. This paper
describes the health promotion programme Socio-educational Groups of Primary Care
for Women (SEGPC-W), and evaluates its implementation in ASTN in the city of
Seville (Spain), as well as the benefits and difficulties of its development
through a documentary analysis and interviews with participating professionals.
PMID- 29329793
TI - Drug use, family support and related factors in university students. A cross
sectional study based on the uniHcos Project data.
AB - OBJECTIVE: To assess the prevalence of illegal drug use in college students on
any previous occasion, during the previous year and the previous month, and to
analyze the relationship between illegal drug use and family support and other
factors. METHODS: A cross-sectional study using data from students participating
in the uniHcos project (n = 3767) was conducted. The prevalence and age of onset
of consumption of cannabis, non-prescription sedatives, stimulants and
depressants was evaluated. Polyconsumption was also assessed. The independent
variables were: family support, age, residence, and employment status. To
determine the factors related to drug use multivariate logistic regression models
stratified by gender were fitted. RESULTS: Differences between men and women in
prevalence of illegal drug use except non-prescription sedatives were observed.
In both genders, less family support was associated with higher consumption of
all drugs, except depressants, and with polyconsumption. To be studying and
looking for work was related to cannabis and stimulant use and to polyconsumption
among women, but only to cannabis use among men. CONCLUSIONS: These results
support the notion that the start of university studies is a particularly
relevant stage in the onset of illegal drug use and its prevention, and that
consumption may be especially associated with family support.
PMID- 29329794
TI - Redox-signals and macrophage biology.
AB - Macrophages are known for their versatile role in biology. They sense and clear
structures that contain exogenous or endogenous pathogen-associated molecular
patterns. This process is tightly linked to the production of a mixture of
potentially harmful oxidants and cytokines. Their inherent destructive behavior
is directed against foreign material or structures of 'altered self', which
explains the role of macrophages during innate immune reactions and inflammation.
However, there is also another side of macrophages when they turn into a tissue
regenerative, pro-resolving, and healing phenotype. Phenotype changes of
macrophages are termed macrophage polarization, representing a continuum between
classical and alternative activation. Macrophages as the dominating producers of
superoxide/hydrogen peroxide and nitric oxide are not only prone to oxidative
modifications but also to more subtle signaling properties of redox-active
molecules conveying redox regulation. We review basic concepts of the enzymatic
nitric oxide and superoxide production within macrophages, refer to their unique
chemical reactions and outline biological consequences not only for macrophage
biology but also for their communication with cells in the microenvironment.
These considerations link hypoxia to the NO system, addressing feedforward as
well as feedback circuits. Moreover, we summarize the role of redox-signaling
affecting epigenetics and reflect the central role of mitochondrial-derived
oxygen species in inflammation. To better understand the diverse functions of
macrophages during initiation as well as resolution of inflammation and to decode
their versatile roles during innate and adaptive immunity with the entire
spectrum of cell protective towards cell destructive activities we need to
appreciate the signaling properties of redox-active species. Herein we discuss
macrophage responses in terms of nitric oxide and superoxide formation with the
modulating impact of hypoxia.
PMID- 29329795
TI - Omega-3 fatty acids and adipose tissue biology.
AB - This review provides evidence for the importance of white and brown adipose
tissue (i.e. WAT and BAT) function for the maintenance of healthy metabolic
phenotype and its preservation in response to omega-3 polyunsaturated fatty acids
(omega-3 PUFA), namely in the context of diseased states linked to aberrant
accumulation of body fat, systemic low-grade inflammation, dyslipidemia and
insulin resistance. More specifically, the review deals with (i) the concept of
immunometabolism, i.e. how adipose-resident immune cells and adipocytes affect
each other and define the immune-metabolic interface; and (ii) the characteristic
features of "healthy adipocytes" in WAT, which are relatively small fat cells
endowed with a high capacity for mitochondrial oxidative phosphorylation,
triacylglycerol/fatty acid (TAG/FA) cycling and de novo lipogenesis (DNL). The
intrinsic metabolic features of WAT and their flexible regulations, reflecting
the presence of "healthy adipocytes", provide beneficial local and systemic
effects, including (i) protection against in situ endoplasmic reticulum stress
and related inflammatory response during activation of adipocyte lipolysis; (ii)
prevention of ectopic fat accumulation and dyslipidemia caused by increased
hepatic VLDL synthesis, as well as prevention of lipotoxic damage of insulin
signaling in extra-adipose tissues; and also (iii) increased synthesis of anti
inflammatory and insulin-sensitizing lipid mediators with pro-resolving
properties, including the branched fatty acid esters of hydroxy fatty acids
(FAHFAs), also depending on the activity of DNL in WAT. The "healthy adipocytes"
phenotype can be induced in WAT of obese mice in response to various stimuli
including dietary omega-3 PUFA, especially when combined with moderate calorie
restriction, and possibly also with other life style (e.g. physical activity) or
pharmacological (e.g. thiazolidinediones) interventions. While omega-3 PUFA could
exert beneficial systemic effects by improving immunometabolism of WAT without a
concomitant induction of BAT, it is currently not clear whether the metabolic
effects of the combined intervention using omega-3 PUFA and calorie restriction
or thiazolidinediones depend also on the activation of BAT function and/or the
induction of brite/beige adipocytes in WAT. It remains to be established why
omega-3 PUFA intervention in type 2 diabetic subjects does not improve insulin
sensitivity and glucose homeostasis despite inducing various anti-inflammatory
mediators in WAT, including the recently discovered docosahexaenoyl esters of
hydroxy linoleic acid, the lipokines from the FAHFA family, as well as several
endocannabinoid-related anti-inflammatory lipids. To answer the question whether
and to which extent omega-3 PUFA supplementation could promote the formation of
"healthy adipocytes" in WAT of human subjects, namely in the obese insulin
resistant patients, represents a challenging task that is of great importance for
the treatment of some serious non-communicable diseases.
PMID- 29329796
TI - The Evolving Face of Myocardial Reperfusion in Acute Coronary Syndromes: A Primer
for the Internist.
AB - Acute coronary syndromes (ACSs) account for a large proportion of disease burden
in the United States and worldwide, and our understanding of ACS management
continues to evolve. In this review we take a practical approach to evaluating
and treating a patient with ACS, focusing on the optimal timing and methods of
coronary reperfusion. Beginning with initial assessment and risk stratification,
a provider managing the patient with ACS must be able to expeditiously decide on
and implement the correct guideline-directed pathway to optimize outcomes. With
an ever-growing body and weight of knowledge in this field, the clinician is
tasked with several challenges. First, there are a variety of pathways of care to
be considered; second, adjunctive medical therapies are expanding; and third,
when coupled with the multiple combinations of adjunctive supportive therapies
for revascularization, the variety of potential therapeutic options can be
overwhelming and confusing. Herein, we carefully review all the relevant
guidelines and the contributing literature, taking a 4-step approach: (1) review
the importance of risk stratification before engaging in a particular strategy of
care, (2) define the reperfusion strategies available, (3) review the specific
agents (antiplatelet and anticoagulant) that support reperfusion strategies, and
(4) apply the strategies of care in the context of the clinical presentation.
PMID- 29329797
TI - Reducing Risk of Dementia in AF-Is Oral Anticoagulation the Key?
PMID- 29329799
TI - Cardiac surgery combined with bypass from the ascending aorta to the bilateral
femoral arteries for severe aorto-iliac occlusion: A case series.
PMID- 29329800
TI - Surgery for extensive, chronic aortic dissection: What about the elephant
(trunks) in the room?
PMID- 29329798
TI - Efficacy of Warfarin Anticoagulation and Incident Dementia in a Community-Based
Cohort of Atrial Fibrillation.
AB - OBJECTIVE: To study the association between time in therapeutic range (TTR)
during warfarin therapy and risk of dementia in a population-based cohort of
incident atrial fibrillation (AF). PATIENTS AND METHODS: We conducted an
observational population-based study of 2800 nondemented patients with incident
AF from January 1, 2000, through December 31, 2010. The association of incident
dementia with warfarin therapy and TTR was examined using Cox proportional
hazards regression models. RESULTS: Mean patient age was 71.2 years; 53% were men
(n=1495), and warfarin was prescribed to 50.5% (n=1414) within 90 days of AF
diagnosis. Incident dementia diagnosis occurred in 357 patients (12.8%) over a
mean +/- SD follow-up of 5.0+/-3.7 years. After adjusting for confounders,
warfarin therapy was associated with a reduced incidence of dementia (hazard
ratio [HR], 0.80; 95% CI, 0.64-0.99). However, only those in the 2 highest
quartiles of TTR were associated with lower risk of dementia. A 10% increase in
TTR with a 10% reduction in time spent in the subtherapeutic (HR, 0.71; 95% CI,
0.64-0.79) and supratherapeutic (HR, 0.67; 95% CI, 0.57-0.79) ranges were
associated with decreased risk of dementia. CONCLUSION: In the community,
warfarin therapy for AF is associated with a 20% reduction in risk of dementia.
Increasing TTR on warfarin is associated with reduced risk of dementia. The risk
of dementia was reduced with a reduction in time spent in subtherapeutic and
supratherapeutic international normalized ratio range. Effective anticoagulation
may prevent cognitive impairment in patients with AF.
PMID- 29329801
TI - More than just numbers: Counting thoracic aortic disease just isn't that simple.
PMID- 29329802
TI - Can use of an administrative database improve accuracy of hospital-reported
readmission rates?
AB - OBJECTIVES: Readmission rates after cardiac surgery are being used as a quality
indicator; they are also being collected by Medicare and are tied to
reimbursement. Accurate knowledge of readmission rates may be difficult to
achieve because patients may be readmitted to different hospitals. In our area,
81 hospitals share administrative claims data; 28 of these hospitals (from 5
different hospital systems) do cardiac surgery and share Society of Thoracic
Surgeons (STS) clinical data. We used these 2 sources to compare the readmissions
data for accuracy. METHODS: A total of 45,539 STS records from January 2008 to
December 2016 were matched with the hospital billing data records. Using the
index visit as the start date, the billing records were queried for any
subsequent in-patient visits for that patient. The billing records included date
of readmission and hospital of readmission data and were compared with the data
captured in the STS record. RESULTS: We found 1153 (2.5%) patients who had STS
records that were marked "No" or "missing," but there were billing records that
showed a readmission. The reported STS readmission rate of 4796 (10.5%)
underreported the readmission rate by 2.5 actual percentage points. The true rate
should have been 13.0%. Actual readmission rate was 23.8% higher than reported by
the clinical database. Approximately 36% of readmissions were to a hospital that
was a part of a different hospital system. CONCLUSIONS: It is important to know
accurate readmission rates for quality improvement processes and institutional
financial planning. Matching patient records to an administrative database showed
that the clinical database may fail to capture many readmissions. Combining data
with an administrative database can enhance accuracy of reporting.
PMID- 29329803
TI - Explant of a ball and cage valve 42 years after initial implant.
PMID- 29329804
TI - A rapid and sensitive fluorometric method for determination of aldehyde oxidase
activity.
AB - Previous research has characterized the important role of aldehyde oxidases (AOX)
in biotransformation of N-heterocyclic therapeutic drugs and environmental
contaminants in mammals. Research pertaining to AOX activity in non-mammalian
vertebrates, however, is scarce, despite its biological role as a potentially
important metabolic pathway for xenobiotics. One of the limiting factors of
research on AOX is that available photometric methods are relatively insensitive,
limited in throughput, and prone to cross-reactivity from other enzymes.
Therefore, this study aimed to develop a novel and improved fluorometric AOX
assay. This assay is based on the conversion of the exogenous aldehyde substrate
4-(dimethyl)amino cinnamaldehyde to its corresponding fluorescent acid by AOX,
and was evaluated using partially purified hepatic cytosol from rat, human, and
rainbow trout. Purification of native cytosol by heat treatment and ammonium
sulfate precipitation resulted in increased specific activity of AOX. Michaelis
Menten kinetic parameters (Kmand Vmax) were comparable to values previously
generated by photometric methods. Furthermore, effects of the inhibitor
hydralazine on AOX activity revealed half maximal inhibitory concentrations
comparable to those generated using conventional methods. Product identity was
confirmed by liquid chromatography and mass spectrometry. In summary, this study
successfully developed a rapid and sensitive assay for determination of AOX
activity in across different vertebrate species that is 4- to 10-fold more
sensitive compared to conventional absorbance-based methods. It can be applied in
environmental, toxicological, and pharmacological studies relating to
identification of AOX substrates, as well as the induction of AOX expression
through drugs and environmental contaminants.
PMID- 29329805
TI - Preparative expression and purification of a nacreous protein N16 and testing its
effect on osteoporosis rat model.
AB - N16, a nacreous protein isolated from Pinctada martensii, is related to nacreous
layer formation. Our previous study indicated that N16 showed dual regulatory
effects by inducing osteoblast biomineralization as well as inhibiting osteoclast
formation. In order to obtain large quantity of N16 for animal experiment and
clinical trial, a fermentation and preparative purification method was
established. The N16 cDNA was cloned to a BL21(DE3)plysE-pET32a vector and grown
in a 20 L fermenter. The medium, temperature, pH and dissolved oxygen (DO) were
optimized. N16 was expressed in inclusion bodies. It was denatured and refolded
in 8 M urea buffer and purified to 97% purity by passing through a gel filtration
column. The glucocorticoid induced osteoporosis (GIO) rat model was used to
investigate the anti-osteoporosis activity of N16 in vivo. Results showed that
the decrease of the bone mineral density (BMD) and the ultimate load was
significantly relieved after N16 treatment. N16 displayed dual regulatory effects
by promoting osteogenesis as well as inhibiting bone resorption in vivo. Our work
will contribute to further clinical studies on N16 for osteoporosis treatment.
PMID- 29329806
TI - Effect of different animal fat and plant oil additives on physicochemical,
mechanical, antimicrobial and antioxidant properties of chitosan films.
AB - Practical application of chitosan-essential oil blend films is limited due to the
uneconomical extraction procedure of essential oils from plants. This study aimed
to produce chitosan films blended with low cost and commercially available oils
and fats consumed in daily human diet (olive, corn and sunflower oils, butter and
animal fats). The study also focused on how physicochemical, biological and
mechanical properties of chitosan blend films were influenced by the
incorporation of oils and fats with varying unsaturation degrees. Possible
interactions of chitosan film matrix with incorporated oils or fats were
investigated. Chitosan-olive oil film showed better surface morphology and higher
thermal stability than the films with other unsaturated oils. Tensile strength,
Young's modulus and elongation at break were improved by 57.2%, 25.1% and 31.7%
for chitosan-olive oil film, respectively. Chitosan-olive oil blend film had the
highest antibacterial activity (almost equal to that of commercial antibiotic
gentamicin). Edible films obtained from by incorporation of natural oils and fats
into chitosan can help produce an environmentally friendly packaging material
that is low cost and easily manufactured.
PMID- 29329807
TI - Nasal adhesive patches - Approach for topical application for dry nasal syndrome.
AB - This present study intended to provide nasal adhesive formulations for the
topical treatment of dry nasal syndrome. Mucoadhesive films were prepared
according to solvent evaporation method consisting of well-known polymers such as
gellan and carboxymethyl cellulose. Mucoadhesive films (A-E) were evaluated in
respect to their physicochemical properties, stability, disintegration behavior
and tensile strength. Moreover, uptake capacity of adhesive films was
investigated according to three assays vapor uptake/ permeability and water
uptake. Mucoadhesive assessment was carried out on porcine nasal mucosa in terms
of adhesion time, wash off resistance and spreadability. Obtained finings
indicated 4.2 (B) > 2.55 (A) > 1.8 (D) > 1.3 (C) > 1(E) fold vapor uptake
ranking. The bioadhesive results indicated a 60-fold (B) > 8.58-fold (C) > 7.42
fold (E) > 1.3-fold (D) improvement in comparison to formulation A. A variety of
humectants such as urea, Aloe vera, allantoin and hyaluronic acid was
incorporated in the formulations. Taken together, nasal adhesive films convinced
with their proficiency of mucoadhesiveness and stability to be suitable in the
management of dry nasal syndrome.
PMID- 29329808
TI - Structural and energetic basis for the molecular recognition of dual synthetic
vs. natural inhibitors of EGFR/HER2.
AB - Activation of EGFR starts by ligand binding at the extracellular domain which
results in homo and heterodimerization, leading to phosphorylation, activation of
downstream signaling pathways which upregulate expression of genes, proliferation
and angiogenesis. Abnormalities in the expression of EGFR play a critical role in
the development of different types of cancer. HER2 is the preferred
heterodimerization partner for EGFR; this biological characteristic together with
the high percentage of structural homology has been exploited in the design of
dual synthetic inhibitors against EGFR/HER2. Herein we combined structural data
and molecular dynamics (MD) simulations coupled to an MMGBSA approach to provide
insight into the binding mechanism between two dual synthetics (lapatinib and TAK
285) and one dual natural inhibitor (EGCG) which target EGFR/HER2. In addition,
we proposed some EGCG derivatives which were filtered through in silico
screening. Structural analysis demonstrated that the coupling of synthetic,
natural or newly designed compounds impacts the conformational space of EGFR and
HER2 differently. Energetic analysis points out that lapatinib and TAK-285 have
better affinity for inactive EGFR than the active EGFR state or HER2, whereas
some EGCG derivatives seem to form binding affinities similar to those observed
for lapatinib or TAK-285.
PMID- 29329809
TI - New N-guanidinium chitosan/silica ionic microhybrids as efficient adsorbent for
dye removal from waste water.
AB - N-guanidinium chitosan acetate, a new chitosan derivative, was prepared via
direct guanylation reaction between chitosan and cyanamide in the presence of
scandium (III) triflate. Treatment of N-guanidinium chitosan acetate with 3
(trihydroxysilyl)-1-propanesulphonic acid followed by sol-gel reaction allowed
accessing N-guanidinium chitosan silica hybrid material. The new ionic
microhybrid was characterized using 13C and 29Si solid state NMR, IR
spectroscopy, scanning electron microscopy and thermogravimetry. Further studies
in the area of separation indicated very high adsorption capacity for cationic
dyes such as methylene blue (MB), with capacities up to 935 mg/g. The adsorption
kinetics can accurately be described by pseudo second-order model. Equilibrium
adsorption data showed a better fit with Langmuir adsorption isotherm model.
Recycling test showed that the ionic microhybrid can be reused in at least five
adsorption-desorption cycles. These results open new perspectives and
possibilities for the design of novel hybrid adsorbents for industrial and
environmental applications.
PMID- 29329810
TI - Facile microencapsulation of olive oil in porous starch granules: Fabrication,
characterization, and oxidative stability.
AB - In this study, starch with porous structures derived from purple sweet potato was
prepared and used as a food-grade polymer for the microencapsulation of olive
oil. The optimal reaction conditions for preparing porous starch were determined
to improve its adsorption capacity as effective microcapsule-wall materials.
Olive oil was then impregnated in microspheres, and loading ratio was optimized
by investigating the restrictive factors, including the mass ratio of olive oil
to porous starch, as well as the embedding temperature and time. The presence of
olive oil in the starch matrix was confirmed by SEM, FTIR, and TGA. Results
demonstrated that the porous starch-based microencapsulation exhibit a stable
olive oil loading ratio and a significant improvement in oxidative stability
compared with free olive oil. The newly-proposed process used in this work was
easy to scale up for developing a new and attractive method for oil protection in
the food industry.
PMID- 29329811
TI - Cardioprotection activity and mechanism of Astragalus polysaccharide in vivo and
in vitro.
AB - Astragalus polysaccharides (ASP) is extracted from Astragalus, and is the main
active ingredient of Astragalus membranaceus. The purpose of this study was to
investigate the protective effect of ASP on rat cardiomyocytes damage induced by
myocardial ischemia and reperfusion injury (MVRI) and isoprenaline(ISO) in vivo
and in vitro. The model of cardiomyocytes damage was induced using MVRI in a rat
in vivo and also using ISO in cell. After ASP intervention, the protective effect
of ASP on cardiomyocytes was evaluated by animal experimental and cell
experimental. The results show that ASP can relieve the increase of cell volume
in myocardium, reduce the apoptosis of cell in myocardial tissue caused by MVRI
in vivo. At the cellular level, ASP can reverse the decrease of cell activity
induced by ISO, inhibit the apoptosis, and decrease the levels of intracellular
reactive oxygen species. Mechanistically at the molecular level, these effects
are elicited via down-regulation of the protein levels of caspase-3 and bax and
up-regulation of the protein levels of bcl-2 in both in vivo and in vitro. These
results demonstrate that ASP has a protective efficacy in MVRI/ISO-treated
cardiomyocytes by inhibiting the apoptosis.
PMID- 29329812
TI - Synergistic effect of polysaccharides, betalain pigment and phenolic compounds of
red prickly pear (Opuntia stricta) in the stabilization of salami.
AB - The aim of this work is to try to substitute some synthetic additives by a
natural extract from red prickly pear (Opuntia stricta) which known by its
richness on bioactive polysaccharides mainly consisting of galactose, rhamnose
and galacturonic acid. This natural fruit has a high content of carbohydrates
above 18.81% FM. It contains also a high level of polyphenols 152.25 +/- 0.26 MUg
QE/mg PPE and flavonoids about 370.60 +/- 0.12 MUg GAE/mg of PPE. In addition,
prickly pear extract (PPE) displayed a strong antioxidant and antimicrobial
activities. These activities are likely due to its phenolic, flavonoid and
carbohydrate contents. Moreover, the addition of 2.5% of PPE, as a natural
colorant and antimicrobial agent in salami formulation, causes a decrease in
hardness and chewiness of the formulated salami. Interestingly, PPE inhibited
bacterial growth in salami stored at 4 degrees C over 30 days. Sensorial
analysis shows that the color, taste and texture of salami prepared with 2.5% of
PPE are markedly more appreciated by panelists. Our results suggest that the
betalain pigment, carbohydrate and phenolic compounds present in PPE could be
used as a natural colorant, antioxidant and antimicrobial agent without change of
the sensory characteristics.
PMID- 29329814
TI - Interaction between structurally different heteroexopolysaccharides and beta
lactoglobulin studied by solution scattering and analytical ultracentrifugation.
AB - Despite a very large number of bacterial exopolysaccharides have been reported,
detailed knowledge on their molecular structures and associative interactions
with proteins is lacking. Small-angle X-ray scattering, dynamic light scattering
and analytical ultracentrifugation (AUC) were used to characterize the
interactions of six lactic acid bacterial heteroexopolysaccharides (HePS-1-HePS
6) with beta-lactoglobulin (BLG). Compared to free HePSs, a large increase in the
X-ray radius of gyration RG, maximum length L and hydrodynamic diameter dH of
HePS-1-HePS-4 mixed with BLG revealed strong aggregation, the extent of which
depended on the compact conformation and degree of branching of these HePSs. No
significant effects were observed with HePS-5 and HePS-6. Turbidity and AUC
analyses showed that both soluble and insoluble BLG-HePS complexes were formed.
The findings provide new insights into the role of molecular structures in
associative interactions between HePSs and BLG which has relevance for various
industrial applications.
PMID- 29329813
TI - Effects of metal ions in tea polysaccharides on their in vitro antioxidant
activity and hypoglycemic activity.
AB - Total tea polysaccharides (TTPS) were extracted from two kinds of pruning leaves
of tea plant and fractionated into neutral tea polysaccharides (TPSI) and acidic
tea polysaccharides (TPSII) by anion exchange resin D315. Some physicochemical
properties, including structure, monosaccharide composition, and molecular weight
distribution, as well as the 4 in vitro antioxidant activities and inhibitory
effects on alpha-glucosidase of above polysaccharides before and after removing
metal ions were investigated. By comparing TTPS and TPSII, we found that they
exhibited different antioxidant activities and inhibitory actions against alpha
glucosidase after their metal ions were removed. However, the in vitro
antioxidant activities and inhibitory effects on alpha-glucosidase of TPSI were
substantially improved. The study can be a certain reference for tea and soil
selection. At the same time, we suggested that pruning leaves of tea plant could
be treated as a potential resource for the development of polysaccharide
antioxidants and hypoglycemic products.
PMID- 29329815
TI - Exploring molecular insights into the interaction mechanism of cholesterol
derivatives with the Mce4A: A combined spectroscopic and molecular dynamic
simulation studies.
AB - Mammalian cell entry protein (Mce4A) is a member of MCE-family, and is being
considered as a potential drug target of Mycobacterium tuberculosis infection
because it is required for invasion and latent survival of pathogen by utilizing
host's cholesterol. In the present study, we performed molecular docking followed
by 100 ns MD simulation studies to understand the mechanism of interaction of
Mce4A to the cholesterol derivatives and probucol. The selected ligands,
cholesterol, 25-hydroxycholesterol, 5-cholesten-3beta-ol-7-one and probucol bind
to the predicted active site cavity of Mce4A, and complexes remain stable during
entire simulation of 100 ns. In silico studies were further validated by
fluorescence-binding studies to calculate actual binding affinity and number of
binding site(s). The non-toxicity of all ligands was confirmed on human monocytic
cell (THP1) by MTT assay. This work provides a deeper insight into the mechanism
of interaction of Mce4A to cholesterol derivatives, which may be further
exploited to design potential and specific inhibitors to ameliorate the
Mycobacterium pathogenesis.
PMID- 29329816
TI - Structural polymorphism of a cytosine-rich DNA sequence forming i-motif
structure: Exploring pH based biosensors.
AB - Sequence recognition and conformational polymorphism enable DNA to emerge out as
a substantial tool in fabricating the devices within nano-dimensions. These DNA
associated nano devices work on the principle of conformational switches, which
can be facilitated by many factors like sequence of DNA/RNA strand, change in pH
or temperature, enzyme or ligand interactions etc. Thus, controlling these DNA
conformational changes to acquire the desired function is significant for
evolving DNA hybridization biosensor, used in genetic screening and molecular
diagnosis. For exploring this conformational switching ability of cytosine-rich
DNA oligonucleotides as a function of pH for their potential usage as biosensors,
this study has been designed. A C-rich stretch of DNA sequence (5'
TCCCCCAATTAATTCCCCCA-3'; SG20c) has been investigated using UV-Thermal
denaturation, poly-acrylamide gel electrophoresis and CD spectroscopy. The SG20c
sequence is shown to adopt various topologies of i-motif structure at low pH.
This pH dependent transition of SG20c from unstructured single strand to
unimolecular and bimolecular i-motif structures can further be exploited for its
utilization as switching on/off pH-based biosensors.
PMID- 29329817
TI - Isothermal chemical denaturation as a complementary tool to overcome limitations
of thermal differential scanning fluorimetry in predicting physical stability of
protein formulations.
AB - Various stability indicating techniques find application in the early stage
development of novel therapeutic protein candidates. Some of these techniques are
used to select formulation conditions that provide high protein physical
stability. Such approach is highly dependent on the reliability of the stability
indicating technique used. In this work, we present a formulation case study in
which we evaluate the ability of differential scanning fluorimetry (DSF) and
isothermal chemical denaturation (ICD) to predict the physical stability of a
model monoclonal antibody during accelerated stability studies. First, we show
that a thermal denaturation technique like DSF can provide misleading physical
stability rankings due to buffer specific pH shifts during heating. Next, we
demonstrate how isothermal chemical denaturation can be used to tackle the above
mentioned challenge. Subsequently, we show that the concentration dependence of
the Gibbs free energy of unfolding determined by ICD provides better predictions
for the protein physical stability in comparison to the often-used Tm (melting
temperature of the protein determined with DSF) and Cm (concentration of
denaturant needed to unfold 50% of the protein determined with ICD). Finally, we
give a suggestion for a rational approach which includes a combination of DSF and
ICD to obtain accurate and reliable protein physical stability ranking in
different formulations.
PMID- 29329818
TI - Hybrid Imaging in Ischemic Heart Disease.
AB - Hybrid imaging for ischemic heart disease refers to the fusion of information
from a single or usually from multiple cardiovascular imaging modalities enabling
synergistic assessment of the presence, the extent, and the severity of coronary
atherosclerotic disease along with the hemodynamic significance of lesions and/or
with evaluation of the myocardial function. A combination of coronary computed
tomography angiography with myocardial perfusion imaging, such as single-photon
emission computed tomography and positron emission tomography, has been adopted
in several centers and implemented in international coronary artery disease
management guidelines. Interest has increased in novel hybrid methods including
coronary computed tomography angiography-derived fractional flow reserve and
computed tomography perfusion and these techniques hold promise for the imminent
diagnostic and management approaches of patients with coronary artery disease. In
this review, we discuss the currently available hybrid noninvasive imaging
modalities used in clinical practice, research approaches, and exciting potential
future technological developments.
PMID- 29329819
TI - The effect of continuous positive airway pressure on spectral encephalogram
characteristics in stroke patients with obstructive sleep apnea.
AB - OBJECTIVES: To evaluate if treatment with continuous positive airway pressure
(CPAP) compared to usual care in stroke patients with obstructive sleep apnea
(OSA) over one month reduces delta and alpha oscillations on quantitative
electroencephalography (EEG) in association with improvements in cognitive or
functional outcomes. METHODS: Spectral EEG analysis was performed in patients
with subacute stroke and OSA randomized to usual care or CPAP treatment from a
previous study. RESULTS: A total of 23 subjects were included. Compared to CPAP
(n = 14), those in the control (n = 9) group demonstrated a significant increase
in alpha power (p = 0.042). There was no between group differences for delta,
theta or beta power. No significant correlation was demonstrated between the
change in alpha power and indices of OSA severity or sleepiness. The increase in
alpha power did not correlate with improvements in outcomes. CONCLUSION: Contrary
to expectations CPAP treatment of OSA did not significantly decrease alpha and
delta oscillations in stroke subjects.
PMID- 29329820
TI - Increased testicular estradiol during the neonatal interval reduces Sertoli cell
numbers.
AB - Previous studies have demonstrated that reducing endogenous testicular estradiol
in neonatal boars would stimulate increased proliferation of Sertoli cells during
the neonatal interval. The objective of this experiment was to determine if
increasing testicular estradiol would have the opposite effect of reducing
Sertoli cell numbers during the neonatal interval. Five littermate pairs of boars
were evaluated with one littermate receiving a silastic implant containing
estradiol and the second receiving only silastic at 1.5 weeks of age. Testes were
recovered at 6.5 weeks of age and Sertoli cell numbers determined. Littermates
treated with exogenous estradiol had approximately two-thirds as many Sertoli
cells as their control littermates (P < 0.001). This is additional evidence for
regulation of Sertoli cell numbers during the neonatal interval by intra
testicular estradiol.
PMID- 29329821
TI - Diminished activation of the right Inferior Parietal Lobule as a neural substrate
of impaired cartoon-jokes comprehension in schizophrenia outpatients.
PMID- 29329822
TI - Lymphoma following clozapine exposure: More information needed.
PMID- 29329823
TI - Atypical presentation of CMV pneumonia in a heart transplant patient.
PMID- 29329824
TI - Total hysterectomy as hematocolpos treatment following bone marrow transplant. A
rare complication of chronic graft-versus-host disease.
PMID- 29329825
TI - Effectiveness and Safety of Transcatheter Aortic Valve Implantation in Patients
With Pure Aortic Regurgitation and Advanced Heart Failure.
AB - Results of transcatheter aortic valve implantation (TAVI) for treatment of severe
noncalcific isolated aortic regurgitation (AR) complicated by advanced heart
failure or cardiogenic shock has been previously reported only in isolated case
reports. Current self-expanding transcatheter aortic valves are designed to treat
aortic valve stenosis, and have also been implanted in cases of severe AR due to
degenerated bioprosthesis and in very few cases of native aortic valves. We
report 13 consecutive inoperable patients with noncalcific, pure AR, and advanced
heart failure treated with emergency percutaneous transfemoral implantation with
self-expandable CoreValves at our institution between July 2012 and September
2017. The immediate and long-term clinical outcome was prospectively assessed
according to the Valve Academic Research Consortium-2 criteria for device success
and safety. All but 3 patients had previous surgery of the aortic root, including
2 implants of Heart Mate-II left ventricle assist device; none had surgical
aortic bioprosthesis at the time of the TAVI. Valve implantation was successful
in 12 of 13 patients (92%) and 1 patient required a second unplanned valve
procedure within 18 hours. Oversizing the prosthesis by approximately 15% yielded
better results with 1 valve. Two patients with left ventricle assist device died
within 30 days of TAVI. All patients who survived to hospital discharge had none
or just mild residual AR, improved their cardiac function, and survived at long
term without recurrence of clinical events. In conclusion, implanting self
expandable transcatheter valves in patients pure AR in this small study was safe
and effective, and represented an important option for inoperable patients with
noncalcific severe AR.
PMID- 29329826
TI - Gender Differences in Presentation, Treatment, and In-Hospital Outcome of
Patients Admitted With Heart Failure Complicated by Atrial Fibrillation (from the
Get With the Guidelines-Heart Failure [GWTG-HF] Registry).
AB - Almost 25% of patients with heart failure (HF) have coexisting atrial
fibrillation (AF), the latter of which may increase morbidity and mortality.
Despite the high prevalence of HF with concomitant AF, this subgroup of patients
remains understudied. This study examines gender differences in presentation,
treatment and in-hospital outcome of patients with HF and AF. The Get With the
Guidelines-Heart Failure (GWTG-HF) database enrolled 6,496 patients with HF who
presented to Cooper University Hospital from 2005 to 2012. Twenty-four percent
(1,561 patients) had concomitant AF. Pearson chi-square tests and the Student T
tests were used to compare patient characteristics by gender. Multivariate
logistic regression was used to predict in-hospital mortality. Six hundred sixty
nine (42.8%) patients with HF and AF were women. Women were older (p <0.001), had
a higher ejection fraction (p <0.001), had systolic hypertension (p <0.001), and
were more likely to have health insurance (p <0.001). Despite a higher CHADS2
score in women (p = 0.007), there was no gender difference in percent of
anticoagulation medications prescribed before admission. Women were less likely
to present with dizziness, lightheadedness, or syncope, and were more likely to
be compliant with medications and diet recommendations before admission. Despite
differences in presentation, co-morbidities, and therapy, in-hospital mortality
was similar between men and women. Decreased appetite or early satiety predicted
in-hospital mortality in women, whereas age, chest pain on admission, and
decreased appetite or early satiety predicted in-hospital mortality in men. In
conclusion, women presenting with HF complicated by AF clinically differ from
men, but despite these differences, both groups shared similar symptom
presentation and in-hospital mortality rates.
PMID- 29329828
TI - Frequency and Prognostic Significance of Acute Kidney Recovery in Patients Who
Underwent Transcatheter Aortic Valve Implantation.
AB - Acute kidney injury (AKI) after transcatheter aortic valve implantation (TAVI) is
associated with increased mortality. As significant hemodynamic improvement may
occur with relief of aortic stenosis, we hypothesized that TAVI patients may
demonstrate the opposite phenomena: acute kidney recovery (AKR). We studied the
incidence and predictors of AKR in post-TAVI patients. A total of 366 consecutive
patients underwent TAVI (January 2012 to January 2017) at a single center. We
defined AKR as a 25% improvement in glomerular filtration rate (GFR) at 48 hours
after TAVI. AKI-creatinine (Cr) was defined as an increase in Cr of >=0.3 mg/dl
at 48 hours. Patients were categorized in 3 groups: AKR (>=25% increase in GFR),
unchanged GFR, and AKI-GFR (inverse definition of AKR, >=25% decrease in GFR).
Multivariable logistic regression defined independent predictors of AKR. AKR
occurred in 1/3 of patients. AKI-Cr occurred in 13% of patients, whereas AKI-GFR
occurred similarly in 15%. AKR and AKI occurred most frequently in patients with
chronic kidney disease (CKD: GFR <= 60 ml/min/1.73 m2). Independent predictors of
AKR-GFR by multivariable analysis were male gender, lack of chronic beta-blocker
utilization, and presence of CKD. Notably, left ventricular dysfunction and
contrast volume were not predictive of AKR. Transfusion occurred less frequently
among patients with AKR compared with patients with AKI-GFR (11% vs 26%, p =
0.03). Death occurred in 0% of AKR patients versus 9.3% of AKI-GFR patients (p
<0.01). In conclusion, this is the first report of AKR after TAVI. Patients with
CKD, male gender, and lack of pre-TAVI beta blockade were more likely to
demonstrate AKR.
PMID- 29329827
TI - Effect of Serum Adiponectin Levels on the Association Between Childhood Body Mass
Index and Adulthood Carotid Intima-Media Thickness.
AB - Childhood obesity predicts adult cardiovascular risk. We hypothesized that the
association between childhood body mass index (BMI) and adult carotid intima
media thickness (CIMT) may be modified by levels of adiponectin, an adipocytokine
that connects body fatness with cardiovascular risk. The study sample included
1,052 adults (71% white and 29% black, 57% female) aged 23.8 to 43.5 years who
were previously examined as children in the Bogalusa Heart Study cohort, with an
average follow-up period of 26.5 (range 14.1 to 29.6) years. Childhood BMI, low
density lipoprotein cholesterol, high-density lipoprotein cholesterol,
triglycerides, and systolic blood pressure were standardized to age-specific z
scores. General linear models were used for data analyses. Childhood BMI (p =
0.034), low-density lipoprotein cholesterol (p <0.001), and systolic blood
pressure (p = 0.005), along with adult adiponectin levels (p = 0.002) were
associated with adult CIMT, adjusted for race, sex, adult age, and cigarette
smoking. Further, adult adiponectin levels significantly modified the association
between childhood BMI and adult CIMT (P for interaction = 0.0003) such that a
significant association between childhood BMI and adult CIMT (p <0.0001) was only
observed in those with adiponectin levels below the median. In conclusion, these
results suggest that serum adiponectin levels modify the association between
childhood obesity and adult atherosclerosis, which has implications for risk
stratification and targeted intervention for obese children with low levels of
adiponectin.
PMID- 29329829
TI - Effectiveness and safety of foam sclerotherapy with 5% ethanolamine oleate in the
treatment of low-flow venous malformations in the head and neck region: a case
series.
AB - The aim of this study was to evaluate the effectiveness and safety of 5%
ethanolamine oleate (EO) foam in the treatment of low-flow venous malformations
in the head and neck region. Seventeen consecutive patients (six male, 11 female)
and 34 low-flow venous malformations were enrolled. The vascular anomalies ranged
between 20mm and 80mm in size. The typical clinical indication was a swelling
(88.2%) with a purple colour (85.3%); the most frequent location was the tongue
(23.5%). Ethanolamine oleate foam was produced via the Tessari method and applied
at 10mg per 1cm to the vascular anomalies. This process resulted in the highest
clinical healing score in 64.7% of cases, and half of the patients reported a
high level of satisfaction (score >9). In the majority of cases (88.2%), the
patients reported that the pain immediately postoperative was mild or moderate.
There were direct relationships between vascular anomaly size and the volume of
EO applied, the number of sessions, and healing (P<0.05). No recurrence was
observed during 6 months of follow-up. This case series showed the effectiveness
and safety of 5% EO foam for the treatment of venous malformations in the head
and neck region.
PMID- 29329830
TI - Theoretical research in structure characteristics of different inhibitors and
differences of binding modes with CBP bromodomain.
AB - The CBP (CREB (cAMP responsive element binding protein) binding protein)
bromodomain (BRD) could recognize and bind with acetyl K382 of human tumor
suppressor protein p53 which the mutation of encoding gene might cause human
cancers. CBP-BRD serves as a promising drug target for several disease pathways
and a series of effective drug have been discovered. In this study, molecular
dynamics (MD) simulations and molecular mechanics generalized born surface area
(MM-GB/SA) approaches were performed to investigate the different binding modes
between five inhibitors with CBP-BRD. Based on the energy and conformation
analyses, a potent core fragment is chosen to act as the starting point for new
inhibitor design by means of LUDI and rational drug design approaches. Then,
T.E.S.T and molinspirition were applied to evaluate oral bioavailability and drug
promiscuity of the new molecules. These results shed light on the idea for
further inhibitor design.
PMID- 29329831
TI - Physicochemical properties, nutritional value and techno-functional properties of
goldenberry (Physalis peruviana) waste powder concise title: Composition of
goldenberry juice waste.
AB - Goldenberry waste powder, contained 5.87% moisture, 15.89% protein, 13.72% fat,
3.52% ash, 16.74% dietary fiber and 61% carbohydrates. Potassium (560 mg/100 g)
was the predominant element followed by sodium (170 mg/100 g) and phosphorus (130
mg/100 g). Amino acid analysis gave high levels of cystine/methionine, histidine
and tyrosine/phenylalanine. Goldenberry waste powder had good levels of the
techno-functional properties including water absorption index, swelling index,
foaming capacity and stability (3.38 g/g, 5.24 ml/g, 4.09 and 72.0%,
respectively). Fatty acids profile showed that linoleic acid was the predominant
fatty acid followed by oleic, palmitic and stearic acids. Iodine value (109.5
g/100 g of oil), acid value (2.36 mg KOH/g of oil), saponification value (183.8
mg KOH/g of oil), peroxide value (8.2 meq/kg of oil) and refractive index
(1.4735) were comparable to those of soybean and sunflower oils. Goldenberry
waste oil exhibited absorbance in the UV range at 100-400 nm.
PMID- 29329832
TI - Effects of cluster thinning on vine photosynthesis, berry ripeness and flavonoid
composition of Cabernet Sauvignon.
AB - Cluster thinning is a common practice for regulating vine yield and grape
quality. The effects of cluster thinning on vine photosynthesis, berry ripeness
and flavonoid composition of V. vinifera L. Cabernet Sauvignon were evaluated
during two seasons. Half of the clusters were removed at pea-size and veraison
relative to two controls, respectively. Both cluster thinning treatments
significantly increased pruning weight and decreased yield. No effects of cluster
thinning on berry growth, ripeness and flavonol composition were observed. Early
cluster thinning decreased the photosynthetic rate at pea-size, but the effect
diminished at post-veraison. Early cluster thinning significantly promoted the
biosynthesis of anthocyanins but decreased the proportion of 3'5'-hydroxylated
and acylated anthocyanins at veraison. Late cluster thinning decreased the
proportions of 3'5'-hydroxylated and acylated anthocyanins. Additionally, Cluster
thinning showed inconsistent effects on flavan-3-ol composition over the two
seasons.
PMID- 29329833
TI - Effect of brewing time and temperature on antioxidant capacity and phenols of
white tea: Relationship with sensory properties.
AB - White tea is highly consumed due to its sensory properties and health benefits,
although most scientific reports don't include the analysis of both properties.
Therefore, the objective of the present study was to unravel the best brewing
conditions for optimal extraction of the bioactive compounds and antioxidant
capacity, while realising the best sensory properties. Infusions of eighty
commercial teas (sold in bags or leaves) were obtained at different time
temperature ratios, studying bioactive compounds (caffeine and individual
catechins), antioxidant capacity and sensory analysis. Brewing at 98 degrees C
for 7 min was the best condition to obtain a high content of antioxidant
polyphenols and pleasant sensory properties. Those teas sold in bags give rise to
tea brews with almost double antioxidant capacity. In conclusion, it is very
important to link sensory and chemical data to obtain optimal sensorial quality
and the highest healthy properties in white tea infusions.
PMID- 29329834
TI - Heterospectral two-dimensional correlation analysis with near-infrared
hyperspectral imaging for monitoring oxidative damage of pork myofibrils during
frozen storage.
AB - Near-infrared (NIR) spectra contain abundant data, heterospectral two-dimensional
correlation (H2D-CS) analysis offers a good way to interpret these data. For the
first time, H2D-CS was used to correlate the NIR hyperspectral imaging (HSI) data
with mid-infrared spectra and to identify feature-related wavebands for
developing models for monitoring the oxidative damage of pork myofibrils during
frozen storage. The HSI images were acquired at frozen state without thawing and
the oxidative damage of myofibrils was assessed by carbonyl content. Results
showed that the simplified PLSR model based on H2D-CS identified feature
wavebands obtained determination coefficient in prediction (R2P) of 0.896 and
root mean square error in prediction (RMSEP) of 0.177 nmol/mg protein, which was
better than the partial least square regression (PLSR) model based on full
wavebands (R2P = 0.856, RMSEP = 0.209 nmol/mg protein). Therefore, H2D-CS was
effective in selecting feature-related wavebands of NIR HSI.
PMID- 29329835
TI - In depth chemical investigation of Glycyrrhiza triphylla Fisch roots guided by a
preliminary HPLC-ESIMSn profiling.
AB - Chemical investigations on Glycyrrhiza spp. have mostly been focused on G. glabra
(typically cultivated in Europe, henceforth called European licorice), G.
uralensis and G. inflata (known as Chinese licorice) with little information on
the constituents of other Glycyrrhiza species. According to the growing interest
in further Glycyrrhiza spp. to be used as sweeteners, the roots of G. triphylla
have been investigated. The LC-ESI/LTQOrbitrap/MS profile of the methanolic
extract of G. triphylla roots guided the isolation of 21 compounds, of which the
structures were elucidated by 1D- and 2D-NMR experiments. Based on this approach,
6 previously unreported compounds including two isoflavones 7,5'-dihydroxy-6,3'
dimethoxy-isoflavone-7-O-beta-d-glucopyranoside (4) and 7,5'-dihydroxy-6,3'
dimethoxy-isoflavone-7-O-(7,8-dihydro-p-hydroxycinnamoyl)-beta-d-glucopyranoside
(7) and four saponins, named licoricesaponins M3 (13), N2 (14), O2 (16) and P2
(18), have been characterized. It is to be noted that the accurate masses of some
compounds here reported for the first time corresponded to those of compounds
previously described in Glycyrrhiza spp. Thus an approach based only on MS
analysis could be misleading; only isolation followed by NMR analysis allowed us
to unambiguously assign the structures of these previously unreported compounds.
PMID- 29329836
TI - Fermented Apulian table olives: Effect of selected microbial starters on
polyphenols composition, antioxidant activities and bioaccessibility.
AB - The effects of fermentation by autochthonous microbial starters on phenolics
composition of Apulian table olives, Bella di Cerignola (BDC), Termite di Bitetto
(TDB) and Cellina di Nardo (CEL) were studied, highlighting also the cultivars
influence. In BDC with starter, polyphenols amount doubled compared with
commercial sample, while in TDB and CEL, phenolics remain almost unchanged. The
main phenolics were hydroxytyrosol, tyrosol, verbascoside and luteolin, followed
by hydroxytyrosol-acetate detected in BDC and cyanidine-3-glucoside and quercetin
in CEL. Scavenger capacity in both DPPH and CAA assays, assessed the highest
antioxidant effect for CEL with starters (21.7 mg Trolox eq/g FW; 8.5 MUmol
hydroxytyrosol eq/100 g FW). The polyphenols were highly in vitro bioaccessible
(>60%), although modifications in their profile, probably for combined effect of
environment and microorganisms, were noted. Finally, fermented table olives are
excellent source of health promoting compounds, since hydroxytyrosol and tyrosol
are almost 8 times more than in olive oil.
PMID- 29329837
TI - The fate and enantioselective behavior of zoxamide during wine-making process.
AB - The fate of zoxamide and its enantiomers were evaluated in detail during wine
making process. The enantiomers of zoxamide were separated and determined by
ultra-high-performance liquid chromatography coupled with tandem mass
spectrometry (UHPLC-MS/MS) after each processing procedure including washing,
peeling, fermentation and clarification. Significant enantioselectivity was
observed in all three treatments with the half-lives of R-zoxamide and S-zoxamide
estimated to be 45.6 and 52.9 h in Group A, 45.0 and 52.1 h in Group B, 56.8 and
70.7 h in Group C, respectively. The results indicated that R-zoxamide degraded
faster than S-zoxamide during the fermentation process. The processing factors
(PFs) of each procedure were generally less than 1, and the PF of the overall
process ranged from 0.019 to 0.051, which indicated that the whole process can
reduce the zoxamide residue in red and white wine obviously. The results could
help facilitate more accurate risk assessments of zoxamide during wine-making
process.
PMID- 29329838
TI - Effect of extraction methods on the chemical components and taste quality of
green tea extract.
AB - The physicochemical properties of tea extracts are significantly affected by the
extraction method. The aim of this study was to compare the effects of static and
dynamic extractions on the concentrations of chemical components and taste
quality of green tea extracts. Our results show that extraction of chemical
components using static extraction follows a pseudo-second-order reaction, while
that of dynamic extraction follows a first-order reaction. The concentrations of
the solids, polyphenols, and free amino acids in green tea extract prepared by
dynamic extraction were much higher, although the overall yields were not
significantly different between the two extraction methods. Green tea extracts
obtained via dynamic extraction were of lower bitterness and astringency, as well
and higher intensities of umami and overall acceptability. These results suggest
that dynamic extraction is more suitable for the processing of green tea
concentrate because of the higher concentration of green tea extract.
PMID- 29329839
TI - Bioaccessibility and potential bioavailability of phenolic compounds from achenes
as a new target for strawberry breeding programs.
AB - Strawberry is a major natural source of bioactive compounds. Botanically,
strawberry is an aggregate fruit consisting of a fleshy floral receptacle that
bears a cluster of real dry fruits (achenes). Existing knowledge on the phenolic
composition of achenes and its contribution to that of the whole fruit is
limited. Also, the gastric and intestinal bioavailability of phenols is poorly
known. In this work, a combination of spectrophotometric and HPLC-DAD methods was
used to analyse the phenolic composition of whole fruits and achenes before and
after in vitro digestion. Five different phenol families were identified. Also,
achenes were found to contribute a sizeable fraction of phenolic acids and
hydrolysable tannins in the whole fruit. Because the mere presence of phenolic
compounds in a food matrix does not ensure their ready absorption and
bioavailability, polyphenol potential bioavailability could be an effective
selection criterion for strawberry breeding programs aimed at improving dietary
healthiness.
PMID- 29329840
TI - Determination of colistin in animal tissues, egg, milk, and feed by ultra-high
performance liquid chromatography-tandem mass spectrometry.
AB - A confirmatory method for the determination of colistin in animal tissues, egg,
milk, and feed was developed and validated. Colistin A and colistin B were
extracted from samples with the mixture of 10% trichloroacetic acid-acetonitrile
and isolated with mixed-mode weak cation exchange cartridge. Analytes were
separated from matrix components using ultra-high performance liquid
chromatography, and detected with electrospray ionization on a triple quadrupole
mass spectrometer. Mean recoveries ranged from 78.0% to 115.6% with intra-day and
inter-day relative standard deviation lower than 8.4% and 12.4%, respectively.
The quantitation limits for different matrices were between 5 and 30 MUg/kg,
which was satisfactory for surveillance monitoring. The developed method was
applied to the analysis of real samples collected from different provinces of
China, and 19 out of 348 samples were found to be contaminated, with the highest
concentration of approximately 12,000 MUg/kg colistin A and 10,000 MUg/kg
colistin B in feed.
PMID- 29329841
TI - Effects of radio frequency assisted blanching on polyphenol oxidase, weight loss,
texture, color and microstructure of potato.
AB - This paper is focused on the effects of radio frequency (RF) heating on the
relative activity of polyphenol oxidase (PPO), weight loss, texture, color, and
microstructure of potatoes. The results showed that pure mushroom PPO was almost
completely inactivated at 80 degrees C by RF heating. The relative activity of
potato PPO reduced to less than 10% with increasing temperature (25-85 degrees
C). Enzyme extract showed the lowest PPO relative activity at 85 degrees C after
RF treatment, followed by the potato cuboids and mashed potato, about 0.19 +/-
0.017%, 3.24 +/- 0.19%, and 3.54 +/- 0.04%, respectively. Circular dichroism
analysis indicated that RF heating changed the secondary structure of PPO, as
alpha-helix content decreased. Both electrode gap and temperature had significant
effect (P < .05) on weight loss, color, and texture of the potato cuboids.
Microstructure analysis showed the changes of potato cell and starch during RF
heating.
PMID- 29329842
TI - Optimization of microwave assisted extraction of Morus nigra L. fruits maximizing
tyrosinase inhibitory activity with isolation of bioactive constituents.
AB - Morus nigra L. is a beneficial food due to rich phenolic components. While aiming
higher yields for bioactive constituents, reduction in terms of raw material,
solvent, time and energy gained more importance to provide a sustainable life for
human and nature. Microwave assisted extraction (MAE) of Morus nigra fruits was
optimized in order to elicit process parameters maximizing bioactive metabolites
and tyrosinase inhibitory activity. Spectrophotometry and UPLC-DAD-ESI-MS/MS
systems were utilized for quantitative analysis of total phenol, flavonoid and
anthocyanin contents. Optimum conditions for MAE were determined as 500 W, 35%
ethanol, 10 min yielding 12.63 mg/g cya-3-glu equiv. anthocyanin and IC50 value
of 1.60 mg/ml for tyrosinase inhibitory activity. Microwave extracts prevailed
better outcomes compared to conventional extraction methods (10.93 mg/g content
with IC50 of 2.81 mg/ml). MAE could be considered as an advanced technique to
obtain extracts from Morus nigra fruits with higher bioactive content and
activity.
PMID- 29329843
TI - Partial substitution of NaCl by KCl and addition of flavor enhancers on probiotic
Prato cheese: A study covering manufacturing, ripening and storage time.
AB - Cheese is a suitable matrix to deliver probiotic strains but it contains a high
amount of sodium. The effect of partial substitution of NaCl by KCl and the
addition of flavor enhancers (l-arginine, yeast and oregano extract) on probiotic
Prato cheese was investigated after 1, 30, and 60 d of refrigerated storage
(immediately after manufacturing, and during ripening and storage).
Microbiological (lactic acid bacteria and probiotic Lactobacillus casei 01 counts
and survival under gastrointestinal conditions), physicochemical (pH,
proteolysis, fatty acids), bioactivity (antioxidant effect and angiotensin I
converting enzyme inhibitory activity), rheological, and water mobility by means
of time domain low-field nuclear magnetic resonance were investigated.
Significant changes in probiotic survival were observed; however, the sodium
reduction and the addition of flavor enhancers did not constitute an obstacle to
L. casei 01 (>108 CFU/g) during storage. Slight changes were observed in
proteolysis, bioactivity, water mobility, texture profile, and fatty acids of the
cheeses as a function of the flavor enhancer added. The sodium reduction and the
supplementation of Prato cheese with probiotic cultures may be an effective
alternative to the production of a potentially functional cheese.
PMID- 29329844
TI - Use of an isoelectric solubilization/precipitation process to modify the
functional properties of PSE (pale, soft, exudative)-like chicken meat protein: A
mechanistic approach.
AB - The functionality of pale, soft, exudative (PSE)-like chicken protein was
improved by isoelectric solubilization/precipitation (ISP) treatment. PSE-like
chicken proteins were solubilized at an acidic pH 3.5 or an alkaline pH 11.0,
followed by precipitating at pH 5.5 and 6.2. PSE-like meat paste was treated as
control (CON). Precipitated at pH 6.2 led to a more elastic gel than at pH 5.5.
Water distribution of ISP-isolated protein was affected by precipitation pH. More
tryptophan residues exposed and -SH was partially oxidized to disulfide bond
after ISP treatment, which led to large aggregates formation and higher viscosity
of ISP isolated proteins than of CON. Absolute zeta potential of alkali-treated
protein was higher than other counterparts, indicating stronger electric
repulsion. ISP treatments could convert alpha-helix structure to relatively
irregular structures. Overall, solubilizing at pH 11.0, combined with a
precipitation pH 6.2 ISP treatment offers a potential for enhanced functionality
of PSE-like chicken protein.
PMID- 29329845
TI - Viscoelastic behaviour of masa from corn flours obtained by nixtamalization with
different calcium sources.
AB - The viscoelastic characteristics of nixtamalized corn masa were assessed by the
dynamic oscillatory test. Masa samples were prepared with flours obtained by
nixtamalization with different calcium sources: Ca(OH)2 (traditional), wood ashes
(classic), CaCO3 (ecological), CaSO4 (ecological), CaCl2 (ecological), and
Ca(C2H5COO)2 (ecological). A sample cooking without calcium source was used as
control. Storage (G') and loss (G'') moduli were higher in masa from traditional
and classic processes indicating a more elastic and viscous masa. Masa of flours
from CaCl2 and Ca(C2H5COO)2 had the lowest values of G' and G''. Viscoelastic
properties were explained in terms of the degree of starch gelatinization, the
hydrolysis of pericarp and fibre content, the calcium-starch and calcium-zein
interactions, as well as the presence of amylose-lipid complexes. Nixtamalization
with Ca(OH)2 and wood ashes gave the best viscoelastic characteristics of masa.
PMID- 29329846
TI - Nutritionally enriched 1,3-diacylglycerol-rich oil: Low calorie fat with
hypolipidemic effects in rats.
AB - An enzymatic process was developed for the preparation of a nutritionally
enriched 1,3-diacylglycerol(DAG)-rich oil from a blend of refined sunflower and
rice bran oils. The process involves hydrolysis of vegetable oil blend using
Candida cylindracea followed by esterification with glycerol using Lipozyme RM1M.
The resultant DAG-rich oil contains 84% of DAG (66% of 1,3-DAG, 18% of 1,2-DAG)
and 16% of triacylglycerol (TAG) along with micro nutrients like gamma-oryzanol,
tocotrienols, tocopherols and phytosterols. Nutritional studies of the DAG-rich
oil were conducted in Wistar rats and compared with sunflower oil (SFO). The
calorific value of the DAG-rich oil was estimated to be 6.45 Kcals/g as against
9.25 Kcals/g for SFO. The serum and liver cholesterol and TAG levels in rats fed
with 1,3-DAG-rich oil were found to be significantly reduced as compared to rats
fed diet containing SFO. We conclude that 1,3-DAG-rich oil is a low calorie fat
and exhibits hypolipidemic effects.
PMID- 29329847
TI - Encapsulation of anthocyanins from bilberries - Effects on bioavailability and
intestinal accessibility in humans.
AB - Anthocyanins are flavonoids that have been suggested to provide beneficial health
effects. The biological activity of anthocyanins is influenced by their
pharmacokinetic properties, but anthocyanins are associated with limited
bioavailability in humans. In the presented study, we investigated how the
encapsulation of bilberry extract (BE), a source of anthocyanins, with either
whey protein or citrus pectin influences the bioavailability and intestinal
accessibility of anthocyanins in humans. We performed an intervention study that
analyzed anthocyanins and their degradation products in the urine, plasma, and
ileal effluent of healthy volunteers and ileostomists (subjects without an intact
colon). We were able to show, that whey protein encapsulation modulated short
term bioavailability and that citrus pectin encapsulation increased intestinal
accessibility during passage through the small intestine and modulated the
formation of the degradation product phloroglucinol aldehyde (PGAL) in human
plasma.
PMID- 29329849
TI - Thermal degradation of chloramphenicol in model solutions, spiked tissues and
incurred samples.
AB - This study investigated the thermal degradation of a veterinary drug,
chloramphenicol, in model solutions (water), as well as in spiked and incurred
mussel tissues to understand its fate in the food supply chain. Thermal
degradation kinetics followed a first-order model in water (e.g. degradation
rate: 0.0018-0.0025 min-1 at 100 degrees C). After 1 h at 100 degrees C, the
percentage degradation in spiked tissues (28.1 +/- 7.1%) was significantly
different (p < .05) from the values in water (14.2 +/- 1.6%) and incurred mussel
tissues (19.0 +/- 4.1%). Using liquid chromatography coupled to high-resolution
accurate mass tandem mass spectrometry, the resulting degradation products of
chloramphenicol were identified in water, spiked and incurred tissues, and were
all different. Therefore, although the use of water models and spiking food
samples may provide some information, our data confirm that "incurred models"
should be systematically implemented to provide reliable information about
veterinary drug residue stability for food safety risk assessments.
PMID- 29329848
TI - Utilization of mixed adsorbents to extend frying oil life cycle in poultry
processing.
AB - The effects were studied of two different adsorbent combinations (com I;
bentonite: activated carbon: celite = 3:4:1 and com II; bentonite: activated
clay: celite = 3:4:1 + 1% citric acid) on the physico-chemical changes of oil
used continuously for deep-fat frying of chicken drumsticks. The results showed
that the % FFA was reduced by 44.3, PV by 50.2, and FOS reading by 40.1% in com I
whereas reductions of 41.6, 44.9, and 32.8%, respectively, were found in com II.
The oil treated with com II exhibited a lighter color than with com I. The
changes of oil color in com I were L* 30.7, a* 1.7, and b* 31.9%; in com II they
were 53.2, 19.1, and 39.5% respectively. The higher the L* observed, the better
the oil quality obtained because of the bleaching ability of adsorbents.
Therefore, the use of such adsorbents is recommended for poultry processing.
PMID- 29329850
TI - GC-MS profiling, descriptive sensory analysis, and consumer acceptance of Costa
Rican papaya (Carica papaya L.) fruit purees.
AB - Volatiles of papaya purees from four Costa Rican cultivars were analysed by solid
phase microextraction and gas chromatography-mass spectrometry. A total of 83
volatiles was assigned in the purees, of which 19 were detected for the first
time as papaya constituents. As revealed by multivariate statistics, i.e.,
principal component analysis (PCA) and partial least squares discriminant
analysis (PLS-DA), the purees may be allocated to terpene- and lactone-rich ('SH
5'), ester-containing ('Criolla'), and intermediate chemotypes ('Pococi' and
'Silvestre'). Descriptive sensory analysis and a consumer acceptance test were
additionally performed. Floral, fruity, and honey-like notes were perceived at
significantly higher intensities in 'SH-5' puree. The latter descriptors strongly
correlated with volatiles discriminating 'SH-5' in the PCA and PLS-DA,
respectively. Consumer acceptance of the papaya purees differed significantly.
'Pococi' and 'SH-5' purees appear to be suitable for improving the nutritional
value of blended fruit juices without impairing their sensory quality.
PMID- 29329851
TI - Chemical characterization of Myrciaria floribunda (H. West ex Willd) fruit.
AB - M. floribunda fruit was studied to characterize its chemical composition. The
chemical composition, bioactive compounds, antioxidant activity and volatiles of
the fruit were determined. The chemical composition was determined according to
AOAC and AOCS, the bioactive compounds by HPLC, the volatiles by GCMS and the
antioxidant activity by ABTS+ and DPPH methods. The chemical composition of the
freeze-dried fruit was 1.89 g.100 g-1, 2.43 g.100 g-1, 4.78 g.100 g-1 and 90.89
g.100 g-1 of ashes, lipids, proteins and total carbohydrates on a dry base,
respectively. The concentration of the carotenoids was 52.22 mg.100 g-1 and for
the flavonoid rutin was 78.56 mg.100 g-1. The gallic and ellagic acid contents
were 5.45 mg.g-1 and 2.21 mg.g-1, respectively. The cis-beta-ocimene corresponded
to 50.90% of the volatiles. The antioxidant activity by ABTS+ method was 550.14
umol Trolox.g-1 and by the DPPH method the EC50 was 85.68 g.g-1. The fruits
presented relevant antioxidant activity, a high concentration of carotenoids and
of rutin.
PMID- 29329852
TI - An integrated in silico/in vitro approach to assess the xenoestrogenic potential
of Alternaria mycotoxins and metabolites.
AB - Xenoestrogenic mycotoxins may contaminate food and feed posing a public health
issue. Besides the zearalenone group, the Alternaria toxin alternariol (AOH) has
been described as a potential mycoestrogen. However, the estrogenicity of
Alternaria toxins is still largely overlooked and further data are needed to
better describe the group toxicity. In the frame of risk assessment, mixed in
silico/in vitro approaches already proved to be effective first-line analytical
tools. An integrated in silico/in vitro approach was used to investigate the
effects of metabolic and chemical modifications on the estrogenicity of AOH.
Among the considered modifications, methylation was found critical for enhancing
estrogenicity (as seen for alternariol monomethyl ether (AME)) while
hydroxylation and glucuronidation had the opposite effect (as seen for 4-hydroxy
AOH and 4-hydroxy AME). The structure-activity relationship analysis provided the
structural rationale. Our results provide insights to design more efficient risk
assessment studies expanding knowledge over the group toxicity.
PMID- 29329853
TI - pH-controlled fermentation in mild alkaline conditions enhances bioactive
compounds and functional features of lentil to ameliorate metabolic disturbances.
AB - Lentil fermentation has a promising potential as a strategy for development of
multifunctional ingredients targeting metabolic syndrome (MetS). Response surface
methodology was applied to optimize lentil fermentation and study its effects on
generation of peptides, soluble phenolics and bioactivities. Fermentation using
Lactobacillus plantarum and Savinase(r) 16 L was carried out at different pH (6.5
8.5) and times (5.5-30 h). Analysis of variance was performed to evaluate linear,
quadratic and interaction effects between fermentation parameters. pH positively
affected peptides, soluble phenolic compounds and antioxidant activity whereas a
negative impact on lipase inhibitory activity was observed (p < .0001). Time
showed positive effect on proteolysis and negatively affected angiotensin I
converting enzyme inhibitory activity of fermented lentil (p < .0001).
Multivariate optimization led to high levels of peptides, soluble phenolics and
bioactivity of fermented lentil at pH 8.5 and 11.6 h. In conclusion, this study
might contribute to the development of functional ingredients from lentil for
MetS management.
PMID- 29329854
TI - Enzymatic preparation of "functional oil" rich in feruloylated structured lipids
with solvent-free ultrasound pretreatment.
AB - In this study, a series of functional oils rich in feruloylated structured lipids
(FSLs) was prepared by enzymatic transesterification of ethyl ferulate (EF) with
triglycerides under ultrasound pretreatment. A conversion of more than 92.7% and
controllable FSLs (3.1%-26.3%) can be obtained under the following conditions:
16% enzyme, substrate ratio 1:5 (oil/EF, mol/mol), 85 degrees C, ultrasound 1 h,
pulse mode 3 s/3s (working/waiting), and 17.0 W/mL. Compared to conventional
mechanical stirring, the activation energy decreased from 50.0 kJ/mol to 40.7
kJ/mol. The apparent kinetic constant increased by more than 13 times, and the
time required for the maximum conversion reduced sharply from 20-60 h to 4-6h,
which was the fastest rate for enzymatic synthesis of FSLs. The antioxidant
activities of the functional oil significantly increased 1.0- to 8.1-fold more
than that of the raw oil. The functional oil could be widely applied in various
fields of functional foods.
PMID- 29329855
TI - Production of three types of krill oils from krill meal by a three-step solvent
extraction procedure.
AB - In this study, a three-step extraction method (separately use acetone, hexane,
and ethanol as extraction solvent in each step) was conducted to selectively
extract three types of krill oils with different compositions. The lipid yields
were 5.08% in step 1, 4.80% in step 2, and 9.11% in step 3, with a total of
18.99%. The krill oil extracted with acetone in step 1 (A-KO) contained the
lowest contents of phospholipids (PL) (2.32%) and n-3 polyunsaturated fatty acids
(PUFA) (16.63%), but the highest levels of minor components (505.00 mg/kg of
astaxanthin, 29.39 mg/100 g of tocopherols, 34.32 mg/100 g of vitamin A and 27.95
mg/g of cholesterol). By contrast, despite having traces of minor components, the
krill oil extracted using ethanol in step 3 (E-KO) was the most abundant in PL
(59.52%) and n-3 PUFA (41.74%). The krill oil extracted using hexane in step 2 (H
KO) expressed medium contents of all the testing indices. The oils showed
significant differences in the antioxidant capacity (E-KO > H-KO > A-KO) which
exhibited positive correlation with the PL content. These results could be used
for further development of a wide range of krill oil products with tailor-made
functions.
PMID- 29329856
TI - Effect of tyrosinase-aided crosslinking on the IgE binding potential and
conformational structure of shrimp (Metapenaeus ensis) tropomyosin.
AB - The present study was performed to determine crosslinking and oxidative reactions
catalyzed by tyrosinase (Tyr), caffeic acid (CA) and their combination with
respect to IgE binding potential and conformational structure of shrimp
tropomyosin (TM). Cross-links and IgE binding potentials were analyzed by SDS
PAGE, western blot and indirect ELISA. While structural changes were
characterized using surface hydrophobicity, ultraviolet (UV), fluorescence and
circular dichroism (CD) spectroscopies. Maximum reduction in the IgG (37.19%) and
IgE binding potentials (49.41%) were observed when treated with 2000 nkat/g Tyr +
CA, as indicated by ELISA analyses. These findings correlated well with the
denaturation of protein, as evident by slight blue shift and alterations in the
ellipticities observed via structural analyses. The results demonstrated that
addition of CA mediator with Tyr pronouncedly enhanced crosslinking, and altered
the conformational structure, thereby mitigated allergenicity of TM, thus showing
promise in developing novel food structures with reduced allergenic potential.
PMID- 29329857
TI - Meat species identification using DNA-luminol interaction and their slow
diffusion onto the biochip surface.
AB - Recently, there has been a growing concern of consumers on the authenticity of
food ingredients including adulteration with porcine and/or its derivatives.
Therefore, this work reports on the development of a novel, simple, sensitive and
rapid luminol-based electrochemiluminescence (ECL) technique for Sus scrofa
(Porcine) DNA detection. Porcine DNA was firstly amplified using loop-mediated
isothermal amplification (LAMP) method and subsequently added to luminol solution
for further ECL analysis for quantification. The DNA-luminol complexes were
formed causing the diffusion of luminol towards the electrode surface to be
slowed down and hindered that resulted in low luminol intensity. The LAMP-ECL
sensor is shown to be highly specific, sensitive (>=0.1 pg/MUL) and rapid (~5 min
for detection). Hence, by employing this principle with carbon screen-printed
electrode (SPE), this technique has a potential to be developed further into a
compact biosensor for the verifying food authenticity.
PMID- 29329858
TI - Mechanical wheat flour modification and its effect on protein network structure
and dough rheology.
AB - Mechanical flour modification is frequently associated with a reduced bread
volume due to changed structural and functional properties of protein and starch.
To clarify the effect of mechanical flour treatment on the protein network
formation at the optimum kneading time (Peaktime), dough was produced with
various mechanical starch modification (MSM) levels and visualized by confocal
laser scanning microscope before being characterized by protein network analysis
(PNA). Dough produced with high MSM showed a reduced branching rate (-14%), a
high end-point rate (+25%) and an increased lacunarity (+139%), indicating a poor
network connectivity with network interruptions. Alterations of the protein
microstructure were closely related to the rheological dough properties. In this
regard, reduced extensibility and resistance to extension of dough produced with
high MSM levels were responsible for decreased dough height (Hm) during
fermentation and thus might be the cause for lower baking volume of bread
produced with high MSM.
PMID- 29329859
TI - Effect of high pressure on structural modifications and enzymatic activity of a
purified X-prolyl dipeptidyl aminopeptidase from Streptococcus thermophilus.
AB - PepX aminopeptidase from Streptococcus thermophilus ACA DC 0022, used in Greek
Feta cheese manufacturing, was purified. PepX comprises two subunits of equal
molecular mass estimated, using SDS-PAGE and native-PAGE electrophoresis, to be
86 kDa. The effects of high pressure processing (100-450 MPa, combined with 20-40
degrees C) on purified PepX activity and structure were studied. Activation of
the enzyme was observed after processing at 100-200 MPa and 20-30 degrees C.
More intense processing conditions led to enzyme inactivation. PepX HP-induced
conformational changes were also investigated through application of Circular
Dichroism spectroscopy (CD). Pressures up to 200 MPa resulted in a structurally
molten globule-like state where PepX maintained its secondary structure but the
tertiary structure was substantially affected and enzyme activity increased. Both
secondary and tertiary structures were affected severely by higher pressures (450
MPa), which reduced enzyme activity.
PMID- 29329860
TI - Ethyl carbamate: An emerging food and environmental toxicant.
AB - Ethyl carbamate (EC), a chemical substance widely present in fermented food
products and alcoholic beverages, has been classified as a Group 2A carcinogen by
the International Agency for Research on Cancer (IARC). New evidence indicates
that long-term exposure to EC may cause neurological disorders. Formation of EC
in food and its metabolism have therefore been studied extensively and analytical
methods for EC in various food matrices have been established. Due to the
potential threat of EC to human health, mitigation strategies for EC in food
products by physical, chemical, enzymatic, and genetic engineering methods have
been developed. Natural products are suggested to provide protection against EC
induced toxicity through the modulation of oxidative stress. This review
summarizes knowledge on the formation and metabolism of EC, detection of EC in
food products, toxic effects of EC on various organs, and mitigation strategies
including prevention of EC-induced tumorigenesis and genotoxicity by natural
products.
PMID- 29329861
TI - In situ characterization of acidic and thermal protein denaturation by infrared
microspectroscopy.
AB - Foods meet acid pH during gastric digestion after cooking. An in situ infrared
microspectroscopy approach was developed to detect the effects of heat and acid
treatments on protein structure separately. Infrared spectra were obtained from
meat samples treated with heat and/or acid, and wavenumbers accounting
independently for the treatments were extracted by principal component
regression. Extreme-acid treatment (pHinitial 2.0) was well predicted (0.5%
error) by a simple ratio of as-observed spectral intensities at 1211 and 1396 cm
1, reflecting a perturbation in the vibration of amino acid residues
(phenylalanine, tyrosine and aspartic acid) by protein unfolding and protonation.
Using the imaging mode of an IR microscope, meat protein acidification was
evidenced with high spatial resolution. The heat effect was well discriminated
from the acid effect by the ratio of as-observed intensities at 1666 and 1697 cm
1 (0.9% error), indicating content of aggregated beta-sheets relative to alpha
helix structure.
PMID- 29329862
TI - Active compounds, antioxidant activity and alpha-glucosidase inhibitory activity
of different varieties of Chaenomeles fruits.
AB - Chaenomeles is an important source for food industry in China, and its planting
area is expanding year by year. This study was conducted to evaluate different
varieties of Chaenomeles by comparing the chemical compositions, antioxidant
activity and alpha-glucosidase inhibitory activity of peels and fleshes from
twelve varieties of Chaenomeles. In the results, peels of Chaenomeles contain
more phenolics, flavonoids and triterpenes, and show better antioxidant activity
and alpha-glucosidase inhibitory activity than their fleshes. All varieties of
Chaenomeles perform different depend on cultivar and climatic conditions.
Oleanolic acid, ursolic acid, protocatechuic acid, rutin, catechin, caffeic acid,
syringic acid, epicatechin, hyperin, quercetin, kaempferol and chlorogenic acid
are main active compounds in Chaenomeles. Zheng'an, Liufu, Zimugua1, Qijiang and
Changjun get Top five scores. This is the first study on the peels and fleshes of
twelve varieties of Chaenomeles, and it gives insights into variety selection in
the planting and production of Chaenomeles.
PMID- 29329863
TI - Preparation of gentiooligosaccharides using Trichoderma viride beta-glucosidase.
AB - The recombinant plasmid pPIC9K-bgl1 containing beta-glucosidase bgl1 from
Trichoderma viride was constructed by overlapping PCR and integrated into Pichia
pastoris KM71. In order to assist the formation of disulfide bonds and thus
improve protein folding efficiency, protein disulfide isomerase pdi was co
expressed in the P. pastoris KM71/pPIC9K-bgl1/pPICZ-A-pdi strain, and
fermentation in flasks resulted in enzyme activity of 143 U/ml. The enzyme
activity of beta-glucosidase reached 1402 U/ml following optimisation of
fermentation conditions in a 3.6 l bioreactor. With 80% glucose as substrate,
gentiooligosaccharides were synthesised by beta-glucosidase-based reverse
hydrolysis. A yield of 130 g/l was achieved with a conversion rate of 16.25%.
With 20% glucose and 40% cellobiose as substrates, gentiooligosaccharides were
synthesised by transglycosylation with a yield of 116 g/l and a conversion rate
of 19.4%.
PMID- 29329864
TI - Antioxidant and anti-freezing peptides from salmon collagen hydrolysate prepared
by bacterial extracellular protease.
AB - Extracted salmon skin collagen was hydrolysed with the free or immobilized
extracellular protease of Vibrio sp. SQS2-3. The hydrolysate exhibited anti
freezing activity (>3 kDa) and antioxidant activity (<3000 Da) after
ultrafiltration. The antioxidant peptide was further purified by size-exclusion
chromatography and found to scavenge DPPH (73.29 +/- 1.03%), OH (72.73 +/-
3.34%,), and intracellular ROS in HUVECs; protect DNA against oxidation-induced
damage; and have an ORAC of 2.78 +/- 0.28 mmol TE/g. The antioxidant peptide
fraction was identified using mass spectrometry, and nineteen salmon collagen
sourced peptides were obtained. Of these, the peptide Pro-Met-Arg-Gly-Gly-Gly-Gly
Tyr-His-Tyr is a novel sequence and was the major component; this peptide was
shown to have antioxidant activity via the ORAC assay (2.51 +/- 0.14 mmol TE/g).
These results suggested that the protease from Vibrio sp. SQS2-3 is suitable for
preparation of anti-freezing peptides and antioxidant peptides in a single step
and represents a comprehensive use of fish skin collagen.
PMID- 29329865
TI - In vitro evaluation of dietary compounds to reduce mercury bioavailability.
AB - Mercury in foods, in inorganic form [Hg(II)] or as methylmercury (CH3Hg), can
have adverse effects. Its elimination from foods is not technologically viable.
To reduce human exposure, possible alternatives might be based on reducing its
intestinal absorption. This study evaluates the ability of 23 dietary components
to reduce the amount of mercury that is absorbed and reaches the bloodstream
(bioavailability). We determined their effect on uptake of mercury in Caco-2
cells, a model of intestinal epithelium, exposed to Hg(II) and CH3Hg standards
and to swordfish bioaccessible fractions. Cysteine, homocysteine, glutathione,
quercetin, albumin and tannic reduce bioavailability of both mercury species.
Fe(II), lipoic acid, pectin, epigallocatechin and thiamine are also effective for
Hg(II). Some of these strategies also reduce Hg bioavailability in swordfish
(glutathione, cysteine, homocysteine). Moreover, extracts and supplements rich in
these compounds are also effective. This knowledge may help to define dietary
strategies to reduce in vivo mercury bioavailability.
PMID- 29329866
TI - Corrigendum to "Effects of chemical composition and baking on in vitro
digestibility of proteins in breads made from selected gluten-containing and
gluten-free flours" [Food Chem. 233 (2017) 514-524].
PMID- 29329867
TI - Corrigendum to "Characterization and screening of pyrrolizidine alkaloids and N
oxides from botanicals and dietary supplements using UHPLC-high resolution mass
spectrometry" [Food Chem. 178 (2015) 136-148].
PMID- 29329868
TI - A procedure for the measurement of Oxygen Consumption Rates (OCRs) in red wines
and some observations about the influence of wine initial chemical composition.
AB - The rates at which wine consumes oxygen are important technological parameters
for whose measurement there are not accepted procedures. In this work, volumes of
8 wines are contacted with controlled volumes of air in air-tight tubes
containing oxygen-sensors and are further agitated at 25 degrees C until O2
consumption is complete. Three exposure levels of O2 were used: low (10 mg/L) and
medium or high (18 or 32 mg/L plus the required amount to oxidize all wine SO2).
In each oxygen level, 2-4 independent segments following pseudo-first order
kinetics were identified, plus an initial segment at which wine consumed O2 very
fast. Overall, multivariate data techniques identify six different Oxygen
Consumption-Rates (OCRs) as required to completely define wine O2 consumption.
Except the last one, all could be modeled from the wine initial chemical
composition. Total acetaldehyde, Mn, Cu/Fe, blue and red pigments and gallic acid
seem to be essential to determine these OCRs.
PMID- 29329869
TI - A new equation for converting the parameter EC50 into the total antioxidant
capacity TEAC and vice versa.
AB - A new equation for converting EC50 into TEAC values and TEAC into EC50 is
presented in this paper. The model was fitted to 180 data points of electron
paramagnetic resonance (EPR) spectroscopy measurements of various food products.
The model was tested basing on 75 EPR spectroscopy measurements. Moreover, the
equation was tested on literature data. The determination coefficient between
EC50cal and EC50exp was found to be R2 = 0.9762, while the determination
coefficient between TEACcal and TEACexp was found to be R2 = 0.9686. Based on
obtained results it can be concluded that the proposed model for converting EC50
into TEAC values and TEAC into EC50 values works properly. This will enable a
comparison of the antioxidant properties of products identified in literature
through the use of different parameters (TEAC, EC50).
PMID- 29329870
TI - 16-O-methylcafestol is present in ground roast Arabica coffees: Implications for
authenticity testing.
AB - High-field and low-field proton NMR spectroscopy were used to analyse lipophilic
extracts from ground roast coffees. Using a sample preparation method that
produced concentrated extracts, a small marker peak at 3.16 ppm was observed in
30 Arabica coffees of assured origin. This signal has previously been believed
absent from Arabicas, and has been used as a marker for detecting adulteration
with robusta. Via 2D 600 MHz NMR and LC-MS, 16-O-methylcafestol and 16-O
methylkahweol were detected for the first time in Arabica roast coffee and shown
to be responsible for the marker peak. Using low-field NMR, robusta in Arabica
could be detected at levels of the order of 1-2% w/w. A surveillance study of
retail purchased "100% Arabica" coffees found that 6 out of 60 samples displayed
the 3.16 ppm marker signal to a degree commensurate with adulteration at levels
of 3-30% w/w.
PMID- 29329871
TI - Isolation of proanthocyanidins from red wine, and their inhibitory effects on
melanin synthesis in vitro.
AB - The red wines made from Vitis vinifera were identified as skin-whitening
effectors by using in vitro assays. OPCs in the wine were evaluated for
tyrosinase activity and melanogenesis. Strong tyrosinase inhibitory activity was
observed in fractions with high oligomeric proanthocyanidin (OPC) content. Among
OPC dimers, a strong inhibitory effect on tyrosinase was observed with OPCs which
contain (+)-catechin as an upper unit. Melanogenesis inhibitory effect was
observed with OPCs which have (-)-epicatechin as upper units. Also, OPC trimers,
upper and middle units joined with 4 -> 8 bonds, showed stronger effects compared
to trimers with 4 -> 6 linkages. Interestingly, (-)-epicatechin-(4beta -> 8)-(-)
epicatechin 3-O-gallate, which is a unique component of grapes has potent
inhibitory effects on both tyrosinase and melanogenesis. Our data provide
structural information about such active compounds. These results suggest that
red wines containing OPC, have high melanogenesis inhibitory effect and are
supposed to have skin-whitening effect.
PMID- 29329872
TI - Development and validation of a HILIC-UV method for the determination of
nucleotides in fish samples.
AB - The aim of this work was the development of a simple, novel and accurate method
for the determination of adenosine triphosphate (ATP) and its first five
catabolites: adenosine diphosphate (ADP), adenosine monophosphate (AMP), inosine
monophosphate (IMP), inosine (Ino) and hypoxanthine (Hx), in fish tissue, based
on hydrophilic interaction liquid chromatography (HILIC). For this purpose, a
stationary phase for polar and hydrophilic compounds (ZIC-pHILIC) was used. The
effect of different chromatographic parameters and the molecular mechanism based
on the van't Hoff plot were examined. The t-test and Dixon's Q-test were applied
in order to examine statistical differences and outlier values. The recovery of
the method ranged between 82.7% and 127% and the %RSD values were lower than 10%
for all analytes determined. The method was applied in frozen sea bream samples
stored at 0-4 degrees C. The Ki-, G-, H- and F values were calculated for the
estimation of the level of fish freshness.
PMID- 29329873
TI - Preparation and characterization of citral-loaded solid lipid nanoparticles.
AB - Citral-loaded solid lipid nanoparticles (citral-SLNs) were prepared via a high
pressure homogenization method, using glyceryl monostearate (GMS) as the solid
lipid and a mixture of Tween 80 (T-80) and Span 80 (S-80) at a weight ratio of
1:1 as the surfactant. The microstructure and properties of the citral-SLNs were
characterized by dynamic light scattering (DLS), scanning electron microscopy
(SEM), differential scanning calorimetry (DSC), Fourier-transform infrared
spectroscopy (FTIR), X-ray diffraction (XRD) and thermal gravimetric analysis
(TGA). The chemical stability of citral in the citral-SLNs was analyzed by solid
phase microextraction gas chromatography (SPME-GC). The GC results showed that
67.0% of the citral remained in the citral-SLN suspensions after 12 days, while
only 8.22% remained in the control. Therefore, the encapsulation of citral in the
solid lipid can enhance its stability in acidic surroundings.
PMID- 29329874
TI - A survey of free glutamic acid in foods using a robust LC-MS/MS method.
AB - An effective and simultaneous liquid chromatography-tandem mass spectrometry (LC
MS/MS) method was used with the aim of quantifying monosodium glutamate (MSG) in
foodstuffs, such as chips, taste cubes, sauces and soups. The results were linear
(R2 = 1), with very low LOD and LOQ values, 1.0 ug/kg, 5.0 ug/kg, respectively.
Excellent repeatability and reproducibility were also achieved. This highly
sensitive and robust LC-MS/MS technique was applied successfully for the
detection and quantification of MSG in a wide variety of foodstuffs. MSG contents
ranged from 0.01 g/100 g to 15.39 g/100 g in food samples. Importantly,
determination of free glutamic acid in the daily diet could also prevent various
side effects associated with consumption of excess free glutamic acid.
PMID- 29329875
TI - Hydrolysers of modified mycotoxins in maize: alpha-Amylase and cellulase induce
an underestimation of the total aflatoxin content.
AB - Aflatoxins are the most potent genotoxic and carcinogenic mycotoxins. To date,
research has only focused on the presence of free aflatoxins in agricultural
commodities. Therefore, the main objective of this study was to investigate the
occurrence of possible modified aflatoxins in maize. Different hydrolysis methods
were applied to convert modified mycotoxins into their free aflatoxins. Eighteen
aflatoxin-contaminated maize samples were incubated with potassium hydroxide,
trifluoromethanesulfonic acid and several enzymes to induce hydrolysis. Potassium
hydroxide caused a total reduction of aflatoxins, while trifluoromethanesulfonic
acid did not lead to an increase in free aflatoxins, neither did treatment with a
protease. However, alpha-amylase and cellulase incubation caused significant
increases in the total free aflatoxin content, 15 +/- 8% and 13 +/- 5%,
respectively. These results show that a small proportion of aflatoxins could be
associated to matrix substances in plants. Consequently, hydrolysis could occur
during food processing and during mammalian digestion, leading to an
underestimation of the total aflatoxin content.
PMID- 29329876
TI - Discrimination of processing grades of olive oil and other vegetable oils by
monochloropropanediol esters and glycidyl esters.
AB - In this study, the processing derived contaminants 2- and 3-monochloropropanediol
(2- and 3-MCPD) esters and glycidyl esters (GEs) were analysed in 84 oil samples
by GC-MS/MS for the discrimination of processing grades of olive oils as a
potential authentication tool. Concentrations of 2- and 3-MCPD esters and GEs
varied in the ranges 0-6 mg/kg, 0-1.5 mg/kg, and 0-1 mg/kg oil, respectively. The
concentrations of the three compounds in lower grade olive oils were
significantly higher (P < .001) than that in EVOO. A similar difference was
observed for other refined and cold-pressed vegetable oils. The limit of fraud
detection of lower grade oils in EVOO was 2% when using 3-MCPD esters, 5% for 2
MCPD esters, and 13-14% for GEs based on calculations of virtual mixtures of the
current sample set. Especially the MCPD esters appear very specific and promising
for the detection of lower processing grade oils in EVOO.
PMID- 29329877
TI - [Attitudes towards cow's milk protein allergy management by spanish
gastroenterologist].
AB - INTRODUCTION: Food allergy is an increasing health problem in the developed
world. Cow's milk protein is the main cause of food allergy in infants. Without
an appropriate diagnostic workup, there is a high risk of both over- and
underdiagnosis and therefore, over and undertreatment. The objective of our study
was to analyze the variability in cow's milk protein allergy (CMPA) management by
pediatric gastroenterologists in Spain. METHODS: A fifty item questionnaire,
including open and closed items in a Likert's scale from 0 to 5, was drafted and
distributed through the Spanish Society for Pediatric Gastroenterology,
Hepatology and Nutrition (SEGHNP) e-mail list. RESULTS: Seventy-three
questionnaires were received back out of 321. Only 3 of the items achieved
concordance greater than 90%. Thirty-three percent considered oral challenge to
be necessary for the diagnosis of CMPA under any circumstance. Twenty-five
percent considered that symptom improvement after cow's milk removal was enough
for the diagnosis. Oral challenge was performed at home by 83.5% in non-IgE
mediated cases. Extensively hydrolyzed casein formulas were the treatment of
choice for 69.9%. Soy formulas were the last option. Almost all respondents were
aware of the existence of clinical guidelines on CMPA, being European Society of
Pediatric Gastroenterology, Hepatology and Nutrition guidelines the most followed
(64.4%). Twenty-three percent considered that their knowledge about allergy was
inadequate. CONCLUSIONS: Although CMPA is a prevalent condition that pediatric
gastroenterologists have been treating for decades, we found a huge variability
on its management. There is potential for improvement in this field among
pediatric gastroenterologist in the future.
PMID- 29329878
TI - Course-, dose-, and stage-dependent toxic effects of prenatal dexamethasone
exposure on fetal articular cartilage development.
AB - Dexamethasone, a synthetic long-acting glucocorticoid, is routinely used for
treating mothers at risk for preterm delivery. However, intrauterine overexposure
to glucocorticoids induces low birth weight and cartilage dysplasia in offspring.
Also, the "critical window" and safe dose of this treatment are largely unknown.
This study investigated the course-, dose-, and stage-dependent toxic effects and
the possible mechanisms of prenatal dexamethasone exposure (PDE) on fetal
development and articular cartilage development. Pregnant mice (C57BL/6) received
subcutaneous injection of dexamethasone (0.8 mg/kg d) once on gestational day
(GD) 15 or once a day from GD 15 to 17, or received various doses of
dexamethasone (0, 0.2, 0.8, and 1.2 mg/kg d) on GD 15-17, or received
dexamethasone (0.8 mg/kg d) at early stage (GD 12-14) or late stage of pregnancy
(GD 15-17). Offspring's knee joints were harvested at birth for morphological
analyses and detection of gene expression. Repeated PDE significantly suppressed
fetal and articular cartilage development, which were characterized by decreased
body weight and body length, coarse articular cartilage surfaces, and reduced
gene and protein expression of Col2a1 and aggrecan. For those newborns treated
with repeated PDE at different doses, the toxic effects on fetal and articular
cartilage development were observed at doses of 0.8 and 1.2 mg/kg d, whereas no
obvious toxic effects were observed at the dose of 0.2 mg/kg d. Moreover, PDE at
0.8 mg/kg d during the early embryonic stage induced stronger toxic effects on
fetal and articular cartilage development, compared with PDE during the late
embryonic stage. Detection of gene expression showed that the TGFbeta signaling
pathway in the articular cartilage was down-regulated after PDE. Taken together,
PDE induces fetal developmental toxicity and articular cartilage developmental
toxicity in a course-, dose-, and stage-dependent manner.
PMID- 29329879
TI - MiR-134 modulates chronic stress-induced structural plasticity and depression
like behaviors via downregulation of Limk1/cofilin signaling in rats.
AB - Increasing evidence has suggested that depression is a neuropsychiatric condition
associated with neuroplasticity within specific brain regions. However, the
mechanisms by which neuroplasticity exerts its effects in depression remain
largely uncharacterized. In the present study we show that chronic stress
effectively induces depression-like behaviors in rats, an effect which was
associated with structural changes in dendritic spines and synapse abnormalities
within neurons of the ventromedial prefrontal cortex (vmPFC). Moreover,
unpredictable chronic mild stress (UCMS) exposure significantly increased the
expression of miR-134 within the vmPFC, an effect which was paralleled with a
decrease in the levels of expression and phosphorylation of the synapse
associated proteins, LIM-domain kinase 1 (Limk1) and cofilin. An intracerebral
infusion of the adenovirus associated virus (AAV)-miR-134-sponge into the vmPFC
of stressed rats, which blocks mir-134 function, significantly ameliorated
neuronal structural abnormalities, biochemical changes and depression-like
behaviors. Chronic administration of ginsenoside Rg1 (40 mg/kg, 5 weeks), a
potential neuroprotective agent extracted from ginseng, significantly ameliorated
the behavioral and biochemical changes induced by UCMS exposure. These results
suggest that miR-134-mediated dysregulation of structural plasticity may be
related to the display of depression-like behaviors in stressed rats. The
neuroprotective effects of ginsenoside Rg1, which produces an antidepressant like
effect in this model of depression, appears to result from modulation of the miR
134 signaling pathway within the vmPFC.
PMID- 29329880
TI - Novel expression of CD11b in epithelial ovarian cancer: Potential therapeutic
target.
AB - OBJECTIVE: The objective of this study was to determine the expression, and
effect of targeting CD11b with a monoclonal antibody in ovarian cancer cells.
METHODS: CD11b expression was determined in epithelial ovarian cancer (EOC) cell
lines and tissues by immunofluorescence and flow cytometry. Cytotoxicity of the
CD11b antibody and synergism with chemothearapeutic drugs were determined by the
MTT Cell Proliferation Assay in human macrophages, normal ovarian epithelial
cells, and in both sensitive and chemoresistant EOC cell lines. Cell migration
was assessed with a scratch assay and in vivo effects of the CD11b antibody was
assessed with a nude mouse ovarian cancer xenograft model. Data was analyzed with
either t-tests or one-way ANOVA. RESULTS: CD11b was unexpectedly expressed in
several EOC lines and tissues, but not normal tissues. Targeting CD11b with its
monoclonal antibody resulted in intriguing cytotoxic effects in sensitive and
chemoresistant EOC lines, while surprisingly not affecting normal cells. More
importantly, the cytotoxicity of the CD11b antibody when combined with
chemotherapeutic drugs (cisplatin or docetaxel) was significantly synergistic, in
both sensitive and chemoresistant EOC cells. The anti-tumorigenic effect of the
CD11b antibody was confirmed in an ovarian cancer nude mouse xenograft model.
CONCLUSION: Here we identify CD11b as a novel target, which selectively induces
cytotoxicity in ovarian cancer cells.
PMID- 29329881
TI - Defining and mitigating the challenges of an older and obese population in
minimally invasive gynecologic cancer surgery.
AB - The incidence of endometrial cancer (EC) is steadily increasing due in large part
to an aging world population and rise in rates of obesity. Patients with obesity
and advancing age can be seen as vulnerable populations, as they are both often
subject to physician bias regarding surgical choices and assumptions regarding
long-term outcomes. As we operate on an older and/or obese patient population, it
is increasingly important that we adopt peri-operative management strategies and
surgical techniques to best serve this complex patient population. Careful
orchestration pre-, intra- and postoperatively is key to successful outcomes in
robotic and laparoscopic surgery. Here, we review existing literature regarding
EC in women with older age and/or obesity, outline recommendations for peri
operative management and common intra-operative issues-specifically common
anesthetic issues surrounding cardiovascular, respiratory and neuromuscular
systems-that are of heightened importance in women with older age and/or obesity.
The goal of this review is to help define and mitigate common complications for
these vulnerable patients with an EC diagnosis who, in accordance with carefully
assessed health risks, can and should be offered standard of care surgery and
treatment.
PMID- 29329882
TI - Prognostic significance of residual lymph node status after definitive
chemoradiotherapy in patients with node-positive cervical cancer.
AB - OBJECTIVE: Lymph node involvement is an important prognostic factor in patients
with cervical cancer. However, the prognostic significance of lymph node response
to chemoradiotherapy remains unclear. We retrospectively analyzed the
relationship between residual lymph node status after definitive
chemoradiotherapy and survival. METHODS: We enrolled 117 patients with node
positive cervical cancer. All patients were treated with definitive
chemoradiotherapy in our institution, from 2006 to 2016. The median follow-up
period was 41months (range, 6-128months). The criterion for a positive lymph node
was defined as a maximum short axis diameter of >=8mm on pretreatment magnetic
resonance imaging (MRI)/computed tomography (CT) scans. Posttreatment pelvic MRI
was obtained 3months after the completion of chemoradiotherapy. Residual primary
tumor was defined as any residual lesion identified upon clinical examination
and/or MRI. Residual lymph node was defined as any lymph node with a short axis
diameter of >=8mm posttreatment, according to MRI/CT. RESULTS: At follow-up,
3months after chemoradiotherapy, we observed residual primary tumor in 30
patients (25.6%), and residual lymph node in 31 patients (26.5%). The presence of
residual lymph node was associated with worse overall survival according to
multivariate analysis (hazard ratio, 3.04; 95% confidence interval, 1.43-6.44;
p=0.004). In the 5-year time-dependent ROC analysis of survival prediction, the
presence of residual lymph node showed an AUC value of 0.72. CONCLUSIONS: The
presence of residual lymph node after chemoradiotherapy was associated with worse
survival in patients with node-positive cervical cancer.
PMID- 29329883
TI - Oxidation, Damage Mechanisms, and Reasons for Revision of Sequentially Annealed
Highly Crosslinked Polyethylene in Total Knee Arthroplasty.
AB - BACKGROUND: Sequentially annealed, highly crosslinked polyethylene (HXLPE) has
been used clinically in total knee arthroplasty (TKA) for over a decade. However,
little is known about the revision reasons; its surface damage mechanisms; or its
in vivo oxidative stability relative to conventional polyethylene. We asked
whether retrieved HLXPE tibial inserts exhibited: (1) similar revision reasons;
(2) improved resistance to surface damage; and (3) improved oxidative stability,
when compared with conventional gamma inert sterilized polyethylene inserts.
METHODS: A total of 456 revised tibial inserts were collected in a multicenter
retrieval program between 2000 and 2016. The implantation time for the HXLPE
components was 1.8 +/- 1.8 years, and for the control inserts it was 3.4 +/- 2.7
years. Revision reasons were assessed based on medical records, radiographs, and
examinations of the retrieved components. Surface damage was assessed using a
semi-quantitative scoring method. Oxidation was measured using Fourier transform
infrared spectroscopy. RESULTS: The tibial inserts in both cohorts were revised
most frequently for loosening, infection, and instability. The most commonly
observed surface damage modes were burnishing, pitting, and scratching. Oxidation
of the HXLPE inserts was, on average, low and similar to the control inserts at
the bearing surface and the stabilizing post. CONCLUSIONS: We observed evidence
of in vivo oxidation in both HXLPE and control tibial inserts. We found no
association between the levels of oxidation and the clinical performance of the
HXLPE tibial components. The findings of this study document the revision
reasons, surface damage modes, and oxidative behavior of sequentially annealed
HXLPE for TKA.
PMID- 29329884
TI - Impurity profiling of drug candidates: Analytical strategies using reversed-phase
and mixed-mode high-performance liquid chromatography methods.
AB - The development of new active pharmaceutical ingredients (API) requires accurate
impurity profiling. Nowadays, reversed-phase HPLC (RPLC) on C18 stationary phase
is the method of first choice for this task and usually employed in generic
screening methods. However, this method sometimes fails, especially when the
target analyte is not sufficiently retained, making impurity analysis difficult
or even impossible. In such cases, a second method must be available. In the
present paper, we compare the merits of RPLC on C18 phase to those of previously
optimized alternative methods, based on the analysis of a large and diverse set
of small-molecule drug candidates. Various strategies are considered: RPLC on C18
phase but with different mobile phase composition (acidic or basic), RPLC with a
pentafluorophenyl stationary phase, or mixed-mode HPLC with both bimodal and
trimodal stationary phases. First, method performances were compared in terms of
response rate (proportion of compounds eluted) and peak shapes for a large set of
synthetic drugs (140) with structural diversity and their orthogonality was
evaluated. Then a subset of compounds (25) containing varied impurity profiles
was used to compare the methods based on the capability to detect impurities and
evaluate the relative purity of the API.
PMID- 29329885
TI - InnOscent system: Advancing flavor analysis using an original gas chromatographic
analytical device.
AB - Despite continuous advances in analytical and physiological knowledge, the
comprehension of an aroma is still a challenge. Gas chromatography coupled to
olfactometry (GC-O) is an efficient method to identify and estimate individual
potential of odorants, but there is a gap between this individual
characterization and the effective contribution of compounds in the mixture,
which is due to complex chemical and perceptual interactions. Therefore,
recombination and omission experiments are often performed to achieve an
understanding of food aromas. In this study, a chromatographic device, developed
to facilitate aroma analysis, is presented. It was configured to perform both (1)
conventional analyses by GC coupled with a mass spectrometer, olfactometric
port(s), and a flame ionization detector (FID), and (2) omission or recombination
experiments. This dual capability is due to the singular configuration of the
system using an ingenious combination of splitter and Deans switch microfluidics
transfer modules, and the existence of multiple outlets. The operational status
of the system was tested using a purposely simple mixture of compounds. The
similarity of retention times (RT) and FID peak areas obtained for each outlet
demonstrates that the multiple outlets of the system are equivalent. The
reproducibility of retention times (RT) and FID peak areas obtained in switching
and non-switching conditions, also demonstrates the efficiency of switching
operations. The validation of the system enables multiple detectors to be
connected to the outlets and complementary information can be obtained from the
eluate. The connection of recovery disposals to the outlets provides fraction
collection and recombination possibilities, which contribute much to the
understanding of aroma-aroma interactions. As an illustration of the InnOscent
system relevance for the comprehension of more complex aromas, the device was
used to study the aroma of a wine made from Cabernet Franc grape variety. An
olfactometric profile was efficiently produced with the device configured as a GC
MS coupled to a dual olfactometric port. The main odorant active compounds were
identified. The omission approach, carried out with the system on isopropyl- and
isobutyl-methoxypyrazines, demonstrates the significant contribution of these
compounds to the aroma of the wine studied, despite an individual perception
among the weakest of the aromagram. A similar approach can be used to evaluate
the contribution of any compound to any aroma. This approach overcomes
constraints of current methodologies associated to reconstituted model solutions
and paves the way for a better understanding of aroma construction.
PMID- 29329886
TI - Solid-phase extraction of chlorophenols in seawater using a magnetic ionic liquid
molecularly imprinted polymer with incorporated silicon dioxide as a sorbent.
AB - A type of magnetic ionic liquid based molecularly imprinted polymer coated on
SiO2 (Fe3O4@SiO2@IL-MIPs) was prepared with 1-vinyl-3-ethylimidazole ionic liquid
as functional monomer, and 1,4-butane-3,3'-bis-1-ethylimidazole ionic liquid as
cross linker, 4-Chlorophenol as template was successfully applied as a selective
adsorbent for selective extraction of 5 chlorophenols in seawater samples by
using the magnetic solid-phase extraction (MSPE) method. 11 types of
Fe3O4@SiO2@IL-MIPs were synthesized and investigated for their different
compositions of functional monomer (such as [C2min][Br], [C2min][BF4],
[C2min][PF6], acrylamide, methacrylic acid and 4-vinyl pyridine) and cross-linker
(such as [C4min2][Br], [C4min2][BF4], [C4min2][PF6], divinylbenzene, and ethylene
glycol dimethacrylate), respectively. The [C2min][BF4] and [C4min2][PF6] based
Fe3O4@SiO2@IL-MIP with the highest extraction efficiencies was applied to the
optimization experiment of MSPE process (including extraction time, adsorbent
mass and desorption solvents). Good linearity was obtained with correlation
coefficients (R2) over 0.9990 and the relative standard deviations for the intra
day and inter-day determination were less than 3.10% with the extraction
recoveries ranged from 85.0% to 98.4%. The results indicated that the proposed
Fe3O4@SiO2@IL-MIPs possesses great identification and adsorption properties, and
could be used as a good sorbent for selective extraction of CPs in environment
waters.
PMID- 29329887
TI - Determination of N-glycans by high performance liquid chromatography using 6
aminoquinolyl-N-hydroxysuccinimidyl carbamate as the glycosylamine labeling
reagent.
AB - Robust, efficient identification and accurate quantification of N-glycans are of
great significance in N-glycomics analysis. Here, a simple and rapid
derivatization method, based on the combination of microwave-assisted
deglycosylation and 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC)
labeling, was developed for the analysis of N-glycan by high performance liquid
chromatography with fluorescence detection (HPLC-FLD). After optimizing various
parameters affecting deglycosylation and derivatization by RNase B, the time for
N-glycan labeling was shortened to 50 min with ~10-fold enhancement in detection
sensitivity comparing to conventional 2-aminobenzoic acid (2-AA) labeling method.
Additionally, the method showed good linearity (correlation coefficients > 0.991)
and reproducibility (RSD < 8.7%). These advantages of the proposed method were
further validated by the analysis of complex samples, including fetuin and human
serum. Investigation of serum N-glycome for preliminary diagnosis of human lung
cancer was conducted, where significant changes of several N-glycans
corresponding to core-fucosylated, mono- and disialylated glycans have been
evidenced by a series of statistical analysis.
PMID- 29329888
TI - Associations between cartilage proteoglycan density and patient outcomes 12months
following anterior cruciate ligament reconstruction.
AB - BACKGROUND: Lower proteoglycan density (PGD) of the articular cartilage may be an
early marker of osteoarthritis following anterior cruciate ligament (ACL)
reconstruction (ACL-R). The purpose this study was to determine associations
between the Knee Injury and Osteoarthritis Outcomes Score (KOOS) and PGD of the
articular cartilage in the femur and tibia 12-months following ACL-R. METHODS: We
evaluated KOOS pain, symptoms, function in activities of daily living (ADL),
function in sport and recreation (Sport), and quality of life (QOL), as well as
PGD using T1rho magnetic resonance imaging in 18 individuals 12.50+/-0.70months
(these are all mean+/-standard deviation) following unilateral ACL-R (10 females,
eight males; 22.39+/-4.19years; Marx Score=10.93+/-3.33). Medial and lateral load
bearing portions of the femoral and tibial condyles were sectioned into three
(anterior, central and posterior) regions of interest (ROIs). T1rho relaxation
times in the ACL-R knee were normalized to the same regions of interest in the
non-surgical knees. Alpha levels were set at P<=0.05. RESULTS: Worse KOOS
outcomes were significantly associated with greater T1rho relaxation time ratios
in the posterior-lateral femoral condyle [pain (r=-0.54), ADL (r=-0.56), Sport
(r=-0.62) and QOL (r=-0.59)] central-lateral femoral condyle [Sport (r=-0.48) and
QOL (r=-0.42)], and the anterior-medial femoral condyle [Sport (r=-0.46) and QOL
(r=-0.40)]. There were no significant associations between the KOOS and T1rho
outcomes for tibial ROI. CONCLUSIONS: Lower PGD of the femoral cartilage in the
ACL-R knees was associated with worse patient-reported outcomes.
PMID- 29329889
TI - Exploring individual adaptations to an anterior cruciate ligament injury
prevention programme.
AB - BACKGROUND: Individual responses to anterior cruciate ligament injury prevention
programmes (ACL IPPs) have received little attention. This study examined the
effects of an ACL IPP on neuromuscular control and lower limb biomechanics during
landing at the group and individual levels. METHODS: Sixteen female athletes were
randomly allocated to training (n=8) or control (n=8) groups. Electromyography,
and three-dimensional kinematic and kinetic data were collected during landing at
two testing sessions. Repeated measures ANOVA and effect sizes (Cohen's d)
examined the effect of the IPP at the group and individual levels. A sub-group
analysis comparing the effect of the IPP on 'high-' (i.e. large peak knee
abduction moment at baseline) versus 'low-risk' individuals was also conducted.
RESULTS: At the group level; the IPP increased activation of the medial
hamstrings prior to landing (p<0.001; d=0.264) and the medial gastrocnemius at
landing (p<0.001; d=0.426), and increased hip external rotation early after
initial contact (p<0.001; d=0.476). Variable adaptations were seen across
individuals within the training group for all variables (p<0.001). The IPP had a
large effect in reducing frontal plane knee moments for 'high-risk' individuals
(d>0.91), however these results did not reach statistical significance (p>0.05).
CONCLUSIONS: The IPP induced adaptations during landing, however, individual data
revealed dissimilar responses to the programme. Individuals displaying a pre
existing high-risk strategy may incur greater benefits from IPPs, yet only if the
programme targets the relevant high-risk strategy.
PMID- 29329890
TI - Pain, motion and function comparison of two exercise protocols for the rotator
cuff and scapular stabilizers in patients with subacromial syndrome.
AB - STUDY DESIGN: Randomized clinical trial. INTRODUCTION: Eccentric exercise (EE)
was shown to be an effective treatment in tendinopathies. However, the evidence
of its effectiveness in subacromial syndrome (SS) is scarce. Moreover, consensus
has not been reached on whether best results for SS are obtained by means of EE
with or without pain. PURPOSE OF THE STUDY: The purpose of this is to compare the
effect on pain, active range of motion (AROM), and shoulder function of an
exercise protocol performed with pain <40 mm Visual Analog Scale (VAS) and
without pain, in patients with SS. METHODS: Twenty-two subjects (mean age: 59
years [Q1 = 48.50-Q3 = 70], 54.5% women) were randomized into a not-painful EE
group (NPEE; G0: n = 11) and a painful EE group (PEE; G1: n = 11). The
intervention lasted 4 weeks. Pain was recorded using VAS; AROM was measured using
a goniometer; and shoulder function using the modified Constant-Murley Score
(CMS) before and after intervention. RESULTS: All dependent variables improved
significantly in both groups (P < .05): NPEE VAS median: pretest = 55.0 posttest
= 28.0; CMS median: pretest = 36.0 posttest = 65.0. PEE VAS median: pretest =
37.0 posttest = 12.0; CMS median: pretest = 35.0 posttest = 59.0. The comparison
between groups showed no significant differences, with small effect size values
(VAS = 0.09; CMS = 0.21; AROM = 0.12-0.43). DISCUSSION: In contrast to the
previous findings, our results suggest that PEE do not add benefit in SS patients
compared to NPEE. CONCLUSION: Our results suggest that both interventions are
effective in terms of pain, function, and shoulder AROM. Furthermore, PEE does
not provide greater benefits. Further studies are needed with long-term follow-up
to reinforce these results.
PMID- 29329891
TI - Medical use of cannabis and cannabinoids containing products - Regulations in
Europe and North America.
AB - In 1937, the United States of America criminalized the use of cannabis and as a
result its use decreased rapidly. In recent decades, there is a growing interest
in the wide range of medical uses of cannabis and its constituents; however, the
laws and regulations are substantially different between countries. Laws
differentiate between raw herbal cannabis, cannabis extracts, and cannabinoid
based medicines. Both the European Medicines Agency (EMA) and the United States
Food and Drug Administration (FDA) do not approve the use of herbal cannabis or
its extracts. The FDA approved several cannabinoid-based medicines, so did 23
European countries and Canada. However, only four of the reviewed countries have
fully authorized the medical use of herbal cannabis - Canada, Germany, Israel and
the Netherlands, together with more than 50% of the states in the United States.
Most of the regulators allow the physicians to decide what specific indications
they will prescribe cannabis for, but some regulators dictate only specific
indications. The aim of this article is to review the current (as of November
2017) regulations of medical cannabis use in Europe and North America.
PMID- 29329892
TI - Pressure to publish in the biomedical scientific field: Ethical conflicts or a
possible obsessive-compulsive disorder?
PMID- 29329893
TI - Effect of short- and long-term diabetes control on in-hospital and one year
mortality rates in hospitalized patients with diabetic foot.
AB - INTRODUCTION: It remains unclear whether diabetic patients with diabetic foot
complications benefit from strict glycemic control during hospitalization The
present study investigates the effect of short- and long-term diabetes control on
hospital outcomes including: in-hospital and one year mortality rates, length of
hospital stay and the rate of repeated admissions. METHODS: Type 2 diabetic
patients (n = 341) were hospitalized for diabetic foot complications at Wolfson
Medical Center over a 5 year period (2008-2012). The adequate short-term glycemic
control was defined as average glucose levels between 110 and 180 mg/dL. HbA1c
values below 7% were defined as adequate long-term glycemic control. RESULTS: The
average glucose levels during hospitalization were 179 +/- 45 mg/dL and 40% of
the measurements were between 110 and 180 mg/dL. Mean admission HBA1c levels were
8.43% +/- 2.26%, and 31% of the values were below 7%. The mean length of hospital
stay was 24.3 +/- 22.6 days, 15.0% of the patients needed surgical intervention
during admission, the in-hospital mortality rate was 10.3%, and the rate of 1
year readmission was 25.1%. Adequate diabetes control during hospitalization was
not significantly associated with reduced in-hospital mortality (hazard ratio,
0.454, 95% confidence interval 0.186-1.103, p = 0.081). However, adequate
diabetes control during hospitalization lead to significantly decreased one year
mortality (hazard ratio, 0.269, 95% confidence interval 0.707-0.101, p = 0.009).
Adequate diabetes control during hospitalization did not affect the length of
hospital stay or the rate of repeated admission. CONCLUSIONS: Improved glucose
control during hospital admission (levels between 110 and 180 mg/dL) was
associated with reduction of one year mortality.
PMID- 29329894
TI - Neoadjuvant Dose Dense MVAC versus Gemcitabine and Cisplatin in Patients with cT3
4aN0M0 Bladder Cancer Treated with Radical Cystectomy.
AB - PURPOSE: Level I evidence supports the usefulness of neoadjuvant cisplatin based
chemotherapy for muscle invasive bladder cancer. Since dose dense MVAC
(methotrexate, vinblastine, doxorubicin and cisplatin) has mostly replaced
traditional MVAC, we compared pathological response and survival rates in
patients with locally advanced bladder cancer who received neoadjuvant
chemotherapy with dose dense MVAC vs gemcitabine and cisplatin. MATERIALS AND
METHODS: We retrospectively reviewed the records of patients with urothelial
cancer who received neoadjuvant chemotherapy and underwent cystectomy at a total
of 20 contributing institutions from 2000 to 2015. Patients with cT3-4aN0M0
disease were selected for this analysis. The rates of ypT0N0 and ypT1N0 or less
were compared between the gemcitabine and cisplatin, and dose dense MVAC
regimens. Two multivariable Cox proportional hazards regression models of overall
mortality were generated using preoperative and postoperative data. RESULTS: Of
the patients who underwent neoadjuvant chemotherapy and radical cystectomy during
the study period 319 met our inclusion criteria. A significantly lower rate of
ypT0N0 was observed in the gemcitabine and cisplatin arm than in the dose dense
MVAC arm (14.6% vs 28.0%, p = 0.005). The rate of ypT1N0 or less was 30.1% for
gemcitabine and cisplatin compared to 41.0% for dose dense MVAC (p = 0.07). The
mean Kaplan-Meier estimates of overall survival in the gemcitabine and cisplatin,
and dose dense MVAC groups were 4.2 and 7.0 years, respectively (p = 0.001). On
multivariable cox regression analysis based on preoperative data patients who
received gemcitabine and cisplatin were at higher risk for death than patients
who received dose dense MVAC (HR 2.07, 95% CI 1.25-3.42, p = 0.003). Lymph node
invasion (HR 1.97, 95% CI 1.15-3.36, p = 0.01) and hydronephrosis (HR 2.18, 95%
CI 1.43-3.30, p <0.001) were also associated with higher risk of death.
CONCLUSIONS: In our retrospective cohort of patients with locally advanced
bladder cancer dose dense MVAC was associated with higher complete pathological
response and improved survival rates compared to gemcitabine and cisplatin. A
clinical trial is warranted to validate these hypothesis generating results to
test the superiority of neoadjuvant dose dense MVAC in patients with locally
advanced bladder cancer.
PMID- 29329895
TI - Long-Term Outcomes of Laser Prostatectomy for Storage Symptoms: Comparison of
Serial 5-Year Followup Data between High Performance System Photoselective
Vaporization and Holmium Laser Enucleation of the Prostate.
AB - PURPOSE: We compared long-term storage symptom outcomes between photoselective
laser vaporization of the prostate with a 120 W high performance system and
holmium laser enucleation of the prostate. We also determined factors influencing
postoperative improvement of storage symptoms in the long term. MATERIALS AND
METHODS: Included in our study were 266 men, including 165 treated with prostate
photoselective laser vaporization using a 120 W high performance system and 101
treated with holmium laser enucleation of the prostate, on whom 60-month followup
data were available. Outcomes were assessed serially 6, 12, 24, 36, 48 and 60
months postoperatively using the International Prostate Symptom Score,
uroflowmetry and the serum prostate specific antigen level. Postoperative
improvement in storage symptoms was defined as a 50% or greater reduction in the
subtotal storage symptom score at each followup visit after surgery compared to
baseline. RESULTS: Improvements in frequency, urgency, nocturia, subtotal storage
symptom scores and the quality of life index were maintained up to 60 months
after photoselective laser vaporization or holmium laser enucleation of the
prostate. There was no difference in the degree of improvement in storage
symptoms or the percent of patients with postoperative improvement in storage
symptoms between the 2 groups throughout the long-term followup. However, the
holmium laser group showed greater improvement in voiding symptoms and quality of
life than the laser vaporization group. On logistic regression analysis a higher
baseline subtotal storage symptom score and a higher BOOI (Bladder Outlet
Obstruction Index) were the factors influencing the improvement in storage
symptoms 5 years after prostate photoselective laser vaporization or holmium
laser enucleation. CONCLUSIONS: Our serial followup data suggest that storage
symptom improvement was maintained throughout the long-term postoperative period
for prostate photoselective laser vaporization with a 120 W high performance
system and holmium laser enucleation without any difference between the 2
surgeries. Also, more severe storage symptoms at baseline and a more severe BOOI
predicted improved storage symptoms in the long term after each surgery.
PMID- 29329896
TI - Open prostatectomy versus 180-W XPS GreenLight laser vaporization: Long-term
functional outcome for prostatic adenomas>80 g.
AB - INTRODUCTION: GreenLight photoselective vaporisation of the prostate (PVP) offers
an endoscopic alternative to open prostatectomy (OP) for treatment of large
adenomas. This study compares long-term functional outcome of both techniques in
patients with Benign prostatic obstruction (BPO)>80g. MATERIAL AND METHOD: Data
from patients who underwent surgical treatment for BPO>80g from January 2010 to
February 2015 at our institution were retrospectively collected and compared
according to surgical technique. Patient's demographics, surgeon's experience,
operative data and long-term functional results were analyzed, using IPSS and
International continence society (ICS) male questionnaire associated with Quality
of life scores (IPSS-QL and ICS-QL). Predictors of long-term outcome were also
assessed. RESULTS: In total, 111 consecutive patients, 57 PVP and 54 OP, were
included in the study with a mean follow-up of 24 and 33 month respectively.
Patient's age, Charlson score, preoperative IPSS and urinary retention rates were
similar. Mean prostatic volume was superior in the OP group (142 versus 103g,
P<0.001). Transfusion rate was lower after PVP (P=0.02), despite a more frequent
anticoagulant use. Length of hospital stay and urinary catheterization were
shorter after PVP (P<0.001), with however a higher rate of recatheterization
(RR=4.74) and rehospitalization (RR=10.42). Long-term scores were better after OP
for IPSS (1 versus 5, P<0.001), IPSS-QL, ICS, ICS-QL. On multivariate analysis,
prostatic residual volume was the only predictor of long-term IPSS but not ICS.
CONCLUSION: Long-term functional outcome are better after OP compared to PVP.
However, PVP offers good results, allowing to safely operate patients taking
anticoagulants, regardless of prostatic volume. Endoscopic enucleation may the
compromise between both techniques. LEVEL OF EVIDENCE: 4.
PMID- 29329897
TI - [Botulinium toxin and idiopathic overactive bladder: Multicentric contempory
management in Bourgogne].
AB - INTRODUCTION: Since 2014, OnabotulinumtoxinA Botox(r) (Allergan, Inc., Irvine,
USA) represents a new therapeutic option for second-line treatment of idiopathic
overactive bladder. The purpose of the current study was to evaluate practices of
surgeons using onabotulinium toxin (BoNTA) in this indication. MATERIAL AND
METHODS: All urogynecology centers of the country were asked in order to list all
patients who were treated since marketing autorisation. Patient symptoms,
previous treatments, paraclinic evaluations, data of surgery and the
characteristics of the follow up were collected and analyzed. RESULTS: Six
centers used BoNTA and five have accepted to participate. Ninety-seven patients
have been identified. Sixty-eight first injections (70 %) were carried out with
the strict frameworf of the marketing autorisation (urinary frequency, urinary
urgency, urinary incontinence). All patients had at least two symptoms. In 69 %,
Botulinum toxin was a second-line treatment after the failure of tibial
neuromodulation or sacral neuromodulation. Urodynamic evaluation was carried out
for 91 % of patients. The search for a post-void residual volume was observed for
59 % of patients during the follow up. CONCLUSION: In our country, BoNTA
injections for idiopathic overactive bladder are mainly effected after tibial
neuromodulation or sacral neuromodulation failure. Diagnostic, operating and
outcome evaluation practices are still very heterogeneous pleading for a greater
standardization of this new therapy in this indication. LEVEL OF EVIDENCE: 3.
PMID- 29329898
TI - [Prognostic of older age for patients with invasive-muscle-bladder cancer and
treated by radical cystectomy].
AB - INTRODUCTION: Bladder tumor is a disease of older persons, but can also occur in
young adults, because certainly an influence of environmental factors and a
change of lifestyle. The aim of our retrospective analysis is to assess and
evaluate the extent of the prognostic impact of age on the carcinological
prognosis of invasive-muscle-bladder cancer treated by total cystotomy. METHODS:
To evaluate the association of patient age with pathological characteristics and
recurrence-free and disease survival, we retrospectively reviewed 345 patients
with invasive bladder cancer between January 2000 and January 2015. RESULTS: We
divided our patients into two groups: patients under 65 years of age=150 cases
(group 1), patients aged 65 years and over=195 cases (group 2). The 3-year
survival rates for patients according to the age groups were 88% and 64%
respectively, end the recurrence-free survival 66% and 28%. When age was analysed
as a categorical variable, was associated with hydronephrosis (P=0.001), advanced
pathological stage (P=0.034), high grade (P=0.026), nodal involvement (P=0.011)
and lymphovascular invasion (P=0.008). The multivariate Cox model analysis showed
that hydronephrosis and pathological stage was prognostic factors of survival
(P=0.012 and P=0.035, respectively). Higher age is significantly associated with
the risk of pathologically advanced disease and poorer global survival.
CONCLUSION: This work allowed us to assert that advanced chronological age is
significantly associated with an advanced pathological stage of the disease
(volume, pT, grade, lymph nodes) and a low overall survival rate. This could be
useful for selecting subjects who would require adjuvant therapy, as well as for
planning early complementary therapies. LEVEL OF EVIDENCE: 3.
PMID- 29329899
TI - Reply.
PMID- 29329900
TI - The call for considering follicular helper T cells in IgG4-related disease.
PMID- 29329901
TI - Effects of orthokeratology on axial length growth in myopic anisometropes.
AB - PURPOSE: To investigate the effect of orthokeratology (ortho-k) lens wear on
axial length (AL) growth in juvenile myopic anisometropes. METHODS: This
retrospective study consisted of two parts. In Part One, 25 anisometropic
participants (mean age, 11.2 +/- 1.9 years; 11 females and 14 males) were fitted
with ortho-k lenses in the more myopic eye only, and the rate of AL growth was
compared between the ortho-k lens wearing eye and the untreated contralateral eye
over an average period of 23.1 +/- 8.3 months. In Part Two, 8 participants who
developed myopia in the contralateral eye received ortho-k treatment in both eyes
for an average of 12 months; the rate of AL growth before and after ortho-k
treatment in the newly developed myopic eye was compared. RESULTS: In Part One,
the rate of AL elongation in the ortho-k treated eye (0.08 +/- 0.15 mm/year) was
significantly slower than in the contralateral eye (0.39 +/- 0.32 mm/year) (P <
0.001). At the completion of Part One, 16 out of 25 participants (64%) developed
myopia in the initially non-myopic eye. In Part Two, the rate of AL elongation
after ortho-k treatment in the newly developed myopic eye (0.20 mm/year) was
significantly slower than that before ortho-k treatment in the same eye (0.49
mm/year) (P = 0.012). CONCLUSION: Ortho-k treatment slows AL growth in the more
myopic eye of anisometropic patients; should the contralateral eye develop myopia
in the future, ortho-k is capable of slowing down AL growth in that eye as well.
PMID- 29329902
TI - Impact of vertical and horizontal malrotation on measurements of anteroposterior
radiographs of the scapula: need for standardized images in modern omometry.
AB - BACKGROUND: An increasing number of parameters measured on anteroposterior
radiographs are used for the evaluation of the bony geometry of the scapula.
Inhomogeneous acquisition of images is common because of the lack of
standardization in radiographic positioning. Images with malrotation around the
horizontal axis of the scapula are particularly frequent. We hypothesized that
malrotated images would result in large variations in measured radiographic
parameters and that image standardization using qualitative and semiquantitative
"omometric" criteria would decrease these variations in measurements. "Omometry"
is a newly introduced umbrella term that contains all standardized measurements
on plain radiographs of the shoulder, analogous to the term "coxometry," which is
widely used for the radiographic assessment of the osseous pelvis and hip.
METHODS: In this experimental, cadaveric radiographic study, 7 dry-bone human
scapula cadaveric specimens from anonymous donors were used to obtain 210
radiographs. We incrementally rotated (steps of 3 degrees ) every scapula around
its horizontal and vertical axis, with a total range of 42 degrees per each
axis. Then, we measured 5 radiographic parameters on every image and observed
their change with malrotation. Furthermore, we introduced 4 omometric criteria
defining an appropriate (presence of >=3 criteria) radiographic image to improve
standardization of scapular image acquisition. RESULTS: Overall, measured values
remained stable within a narrow range of +/-9 degrees of malrotation. Beyond
this range, values of all parameters significantly deviated (>+/-2 degrees ) from
the initial value. Measurements on appropriate images were significantly less
prone to deviation. Within the appropriate images, those with 4 criteria showed a
higher specificity than those with 3 criteria. CONCLUSION: There is significant
variation in values of measured radiographic parameters on anteroposterior
radiographs of the scapula with substantially malrotated images. With the use of
the 4 newly introduced semiquantitative and qualitative omometric criteria, which
define an appropriate image, reliability of the measured parameters can be
significantly improved.
PMID- 29329903
TI - Response to Laumonerie et al regarding: "Rare implant-specific complications of
the MoPyC radial head prosthesis".
PMID- 29329904
TI - Assembly, maturation, and degradation of the supraspinatus enthesis.
AB - The development of the rotator cuff enthesis is still poorly understood. The
processes in the early and late developmental steps are gradually elucidated, but
it is still unclear how cell activities are coordinated during development and
maturation of the structured enthesis. This review summarizes current knowledge
about development and age-related degradation of the supraspinatus enthesis.
Healing and repair of an injured and degenerated supraspinatus enthesis also
remain a challenge, as the original graded transitional tissue of the
fibrocartilaginous insertion is not re-created after the tendon is surgically
reattached to bone. Instead, mechanically inferior and disorganized tissue forms
at the healing site because of scar tissue formation. Consequently, the enthesis
never reaches mechanical properties comparable to those of the native enthesis.
So far, no novel biologic healing approach has been successful in enhancing
healing of the injured enthesis. The results revealed in this review imply the
need for further research to pave the way for better treatment of patients with
rotator cuff disorder.
PMID- 29329905
TI - Consensus Recommendations for Evaluation, Interpretation, and Utilization of
Computed Tomography and Magnetic Resonance Enterography in Patients With Small
Bowel Crohn's Disease.
AB - Computed tomography and magnetic resonance enterography have become routine small
bowel imaging tests to evaluate patients with established or suspected Crohn's
disease, but the interpretation and use of these imaging modalities can vary
widely. A shared understanding of imaging findings, nomenclature, and utilization
will improve the utility of these imaging techniques to guide treatment options,
as well as assess for treatment response and complications. Representatives from
the Society of Abdominal Radiology Crohn's Disease-Focused Panel, the Society of
Pediatric Radiology, the American Gastroenterological Association, and other
experts, systematically evaluated evidence for imaging findings associated with
small bowel Crohn's disease enteric inflammation and established recommendations
for the evaluation, interpretation, and use of computed tomography and magnetic
resonance enterography in small bowel Crohn's disease. This work makes
recommendations for imaging findings that indicate small bowel Crohn's disease,
how inflammatory small bowel Crohn's disease and its complications should be
described, elucidates potential extra-enteric findings that may be seen at
imaging, and recommends that cross-sectional enterography should be performed at
diagnosis of Crohn's disease and considered for small bowel Crohn's disease
monitoring paradigms. A useful morphologic construct describing how imaging
findings evolve with disease progression and response is described, and standard
impressions for radiologic reports that convey meaningful information to
gastroenterologists and surgeons are presented.
PMID- 29329906
TI - Development of a quick bioassay for the evaluation of transmission properties of
acquired prion diseases.
AB - Evaluation of transmission properties is important for the differential diagnosis
of a subgroup of acquired Creutzfeldt-Jakob disease (CJD) with methionine
homozygosity at polymorphic codon 129 of the PRNP gene, an intermediate type
abnormal prion protein (PrP), and kuru plaques, denoted as acquired CJD-MMiK. The
present study aimed to develop a quick evaluation system of the transmission
properties of acquired CJD-MMiK. In the PrP-humanized mice intraperitoneally
inoculated with brain homogenates from an acquired CJD-MMiK patient, accumulation
of abnormal PrP was observed in follicular dendritic cells of the spleen at 75
days post-inoculation. The transmission properties of acquired CJD-MMiK were
quite different from those of sporadic CJD with the same PRNP codon 129 genotype.
Moreover, even at 14 days post-inoculation, the characteristic transmission
properties of acquired CJD-MMiK could be detected. These findings suggest that
the bioassay using follicular dendritic cells of the spleen, named as a FDC
assay, can be an easy, time-saving, and useful method to distinguish acquired CJD
MMiK from sporadic CJD.
PMID- 29329907
TI - Influence of motor imagery on spinal reflex excitability of multiple muscles.
AB - The effects of motor imagery on spinal reflexes such as the H-reflex are unclear.
One reason for this is that the muscles that can be used to record spinal
reflexes are limited to traditional evoking methods Recently, transcutaneous
spinal cord stimulation has been used for inducing spinal reflexes from multiple
muscles and we aimed to examine the effect of motor imagery on spinal reflexes
from multiple muscles. Spinal reflexes evoked by transcutaneous spinal cord
stimulation were recorded from six muscles from lower limbs during motor imagery
of right wrist extension and ankle plantarflexion with maximum isometric
contraction. During both imaginary tasks, facilitation of spinal reflexes was
detected in the ankle ipsilateral plantarflexor and dorsiflexor muscles, but not
in thigh, toe or contralateral lower limb muscles. These results suggest that
motor imagery of isometric contraction facilitates spinal reflex excitability in
muscles of the ipsilateral lower leg and the facilitation does not correspond to
the imaginary involved muscles.
PMID- 29329908
TI - Anatomical evidence for lateral hypothalamic innervation of the pontine A7
catecholamine cell group in rat.
AB - Substantial behavioral evidence exists to support the idea that the lateral
hypothalamus (LH) makes axonal connection with spinally-projecting noradrenergic
neurons of the A7 catecholamine cell group in the pons. Through this putative
projection, the LH modulates nociception via alpha1- and alpha2-adrenoceptors in
the dorsal horn. We used double-label immunocytochemistry to demonstrate that
axons from the LH labeled with the anterograde tracer biotinylated dextran amine
(BDA) appose tyrosine hydroxylase-immunoreactive (TH-ir) neuron profiles in the
A7 area. Other pontine areas labeled with BDA included the dorsomedial tegmental
area, the pontine reticular nucleus, oral part, the caudal aspect of the dorsal
raphe, the periaqueductal grey and the A6 area. To confirm the findings of the
brightfield experiment, we used confocal microscopy to identify axons from the LH
labeled with the anterograde tracer Fluoro-Ruby co-localized with TH-ir dendrites
and cell bodies in the A7 cell group. These findings provide an anatomical
substrate for behavioral studies in which stimulation of the LH modifies
nociception in the spinal cord via norepinephrine.
PMID- 29329911
TI - mRNA expression and metabolic regulation of npy and agrp1/2 in the zebrafish
brain.
AB - Neuropeptide Y (NPY) is an evolutionarily conserved neuropeptide implicated in
feeding regulation in vertebrates. In mammals, NPY neurons coexpress Agouti
related protein (AgRP) in the arcuate nucleus of the hypothalamus, and NPY/AgRP
neurons activate orexigenic signaling to increase food intake. Zebrafish express
npy and two agrp genes, agrp1 and agrp2, in the brain. Similar to mammals, NPY
and AgRP1 act as orexigenic factors in zebrafish, but the exact distribution of
NPY and AgRP neurons in the zebrafish brain and the regulation of these genes by
metabolic states remain unclear. In this study, we analyzed the tissue
distribution of npy, agrp1, and agrp2 mRNA in the brain of larval and adult
zebrafish. We detected the expression of agrp1, but not npy, in the hypothalamus
of larval zebrafish. In the adult zebrafish brain, npy mRNA expression was
detected in the dorsal area of the periventricular and lateral hypothalamus, but
fasting induced upregulation of npy only in the lateral hypothalamus, indicating
that NPY neurons in this area are implicated in feeding regulation. However,
consistent with the findings in larval zebrafish, NPY neurons in the hypothalamus
did not coexpress AgRP1. In contrast, fasting resulted in a dramatic increase in
AgRP1 neurons in the ventral periventricular hypothalamus, which do not coexpress
NPY. In addition, we found for the first time that npy- and agrp1-expressing
neurons function as GABAergic inhibitory neurons in zebrafish, as they do in
mammals. Taken together, our results show that the zebrafish NPY/AgRP system is
involved in appetite regulation. In addition, our data suggest that although npy
and agrp1 were initially expressed in distinct neurons, evolution has resulted in
their coexpression in mammalian hypothalamic neurons.
PMID- 29329910
TI - The effects of exercise intensity and post-exercise recovery time on cortical
activation as revealed by EEG alpha peak frequency.
AB - Acute physical exercise (APE) induces an increase in the individual alpha peak
frequency (iAPF), a cortical parameter associated with neural information
processing speed. The aim of this study was to further scrutinize the influence
of different APE intensities on post-exercise iAPF as well as its time course
after exercise cessation. 95 healthy young (18-35 years) subjects participated in
two randomized controlled experiments (EX1 and EX2). In EX1, all participants
completed a graded exercise test (GXT) until exhaustion and were randomly
allocated into different delay groups (immediately 0, 30, 60 and 90 min after
GXT). The iAPF was determined before, immediately after as well as after the
group-specific delay following the GXT. In EX2, participants exercised for 35 min
at either 45-50%, 65-70% or 85-90% of their maximum heart rate (HRmax). The iAPF
was determined before, immediately after as well as 20 min after exercise
cessation. In EX1, the iAPF was significantly increased immediately after the GXT
in all groups. This effect was not any more detectable after 30 min following
exercise cessation. In EX2, a significant increase of the iAPF was found only
after high-intensity (85-90% HRmax) exercise. The results indicate intense or
exhaustive physical exercise is required to induce a transient increase in the
iAPF that persists about 30 min following exercise cessation. Based on these
findings, further research will have to scrutinize the behavioral implications
associated with iAPF modulations following exercise.
PMID- 29329913
TI - Predicting Extubation Outcomes-A Model Incorporating Heart Rate Characteristics
Index.
AB - OBJECTIVE: To test the hypothesis that in neonates on mechanical ventilation,
heart rate characteristics index (HRCi) can be combined with a clinical model for
predicting extubation outcomes in neonates. STUDY DESIGN: HRCi and clinical data
for all intended intubation-extubation events (episodes) were retrospectively
analyzed between June 2014 and January 2015. Each episode started 6 hours pre
extubation or at the time of primary intubation if ventilation duration was
shorter than 6 hours (baseline). The episodes ended at 72 hours postextubation
for successful extubations or at reintubation for failed extubations. Mean of 6
hourly epoch HRCi-scores (baseline) or fold-changes (postextubation) were
analyzed. Results are expressed as medians (IQR) for continuous data and
proportions for categorical data. Multivariable logistic regression mixed model
was used for statistical analysis. RESULTS: Sixty-six infants contributed to 96
episodes (18 failed extubations, 78 successful extubations) in the study. Failed
extubations had significantly longer duration of ventilation (65.3 hours, 19.94
158.2 vs 38.4, 16.5-71.3) and more culture positive sepsis (33.3% vs 3.8%) than
successful extubations. Baseline HRCi scores (1.68, 1.29-2.45 vs 0.95, 0.54-1.86)
and postextubation epoch-1 fold changes (1.25, 0.94-1.55 vs 0.94, 0.82-1.11) were
higher in failed extubations compared with successful extubations. Multivariable
linear mixed-effects regression was used to create prediction models for success
of extubation, using relevant variables. CONCLUSIONS: The baseline and
postextubation HRCi were significantly higher in neonates with extubation failure
compared with those who succeeded. Models using HRCi and clinical variables to
predict extubation success may add to the confidence of clinicians considering
extubation.
PMID- 29329914
TI - Never Forget the Optic Fundi in Tuberculosis!
PMID- 29329912
TI - Identification and fate mapping of the pancreatic mesenchyme.
AB - The murine pancreas buds from the ventral embryonic endoderm at approximately
8.75 dpc and a second pancreas bud emerges from the dorsal endoderm by 9.0 dpc.
Although it is clear that secreted signals from adjacent mesoderm-derived sources
are required for both the appropriate emergence and further refinement of the
pancreatic endoderm, neither the exact signals nor the requisite tissue sources
have been defined in mammalian systems. Herein we use DiI fate mapping of
cultured murine embryos to identify the embryonic sources of both the early
inductive and later condensed pancreatic mesenchyme. Despite being capable of
supporting pancreas induction from dorsal endoderm in co-culture experiments, we
find that in the context of the developing embryo, the dorsal aortae as well as
the paraxial, intermediate, and lateral mesoderm derivatives only transiently
associate with the dorsal pancreas bud, producing descendants that are decidedly
anterior to the pancreas bud. Unlike these other mesoderm derivatives, the axial
(notochord) descendants maintain association with the dorsal pre-pancreatic
endoderm and early pancreas bud. This fate mapping data points to the notochord
as the likely inductive source in vivo while also revealing dynamic morphogenetic
movements displayed by individual mesodermal subtypes. Because none of the
mesoderm examined above produced the pancreatic mesenchyme that condenses around
the induced bud to support exocrine and endocrine differentiation, we also sought
to identify the mesodermal origins of this mesenchyme. We identify a portion of
the coelomic mesoderm that contributes to the condensed pancreatic mesenchyme. In
conclusion, we identify a portion of the notochord as a likely source of the
signals required to induce and maintain the early dorsal pancreas bud,
demonstrate that the coelomic mesothelium contributes to the dorsal and ventral
pancreatic mesenchyme, and provide insight into the dynamic morphological
rearrangements of mesoderm-derived tissues during early organogenesis stages of
mammalian development.
PMID- 29329909
TI - The signaling role for chloride in the bidirectional communication between
neurons and astrocytes.
AB - It is well known that the electrical signaling in neuronal networks is modulated
by chloride (Cl-) fluxes via the inhibitory GABAA and glycine receptors. Here, we
discuss the putative contribution of Cl- fluxes and intracellular Cl- to other
forms of information transfer in the CNS, namely the bidirectional communication
between neurons and astrocytes. The manuscript (i) summarizes the generic
functions of Cl- in cellular physiology, (ii) recaps molecular identities and
properties of Cl- transporters and channels in neurons and astrocytes, and (iii)
analyzes emerging studies implicating Cl- in the modulation of neuroglial
communication. The existing literature suggests that neurons can alter astrocytic
Cl- levels in a number of ways; via (a) the release of neurotransmitters and
activation of glial transporters that have intrinsic Cl- conductance, (b) the
metabotropic receptor-driven changes in activity of the electroneutral cation-Cl-
cotransporter NKCC1, and (c) the transient, activity-dependent changes in glial
cell volume which open the volume-regulated Cl-/anion channel VRAC. Reciprocally,
astrocytes are thought to alter neuronal [Cl-]i through either (a) VRAC-mediated
release of the inhibitory gliotransmitters, GABA and taurine, which open neuronal
GABAA and glycine receptor/Cl- channels, or (b) the gliotransmitter-driven
stimulation of NKCC1. The most important recent developments in this area are the
identification of the molecular composition and functional heterogeneity of brain
VRAC channels, and the discovery of a new cytosolic [Cl-] sensor - the Wnk family
protein kinases. With new work in the field, our understanding of the role of Cl-
in information processing within the CNS is expected to be significantly updated.
PMID- 29329915
TI - Observed variation in N95 respirator use by nurses demonstrating isolation care.
AB - Video review and scoring was used to evaluate the behaviors of nurses wearing N95
filtering face piece respirators while providing isolation care in a simulated
patient care environment. This study yielded a detailed description of behaviors
related to N95 respirator use in a health care setting. Developing a more robust
and systematic behavior analysis tool for use in demonstration, simulation, and
clinical care would allow for improved respiratory protection of health care
workers.
PMID- 29329917
TI - Comments on incidence and risk factors for infection in spine surgery: A
prospective multicenter study of 1,764 instrumented spine procedures.
PMID- 29329916
TI - Impact of the International Nosocomial Infection Control Consortium's
multidimensional approach on rates of ventilator-associated pneumonia in 14
intensive care units in 11 hospitals of 5 cities within Argentina.
AB - BACKGROUND: To analyze the impact of the International Nosocomial Infection
Control Consortium (INICC) multidimensional approach (IMA) on ventilator
associated pneumonia (VAP) rates in 11 hospitals within 5 cities of Argentina
from January 2014-April 2017. METHODS: A multicenter, prospective, before-after
surveillance study was conducted through the use of International Nosocomial
Infection Control Consortium Surveillance Online System. During baseline, we
performed outcome surveillance of VAP applying the definitions of the Centers for
Disease Control andPrevention's National Healthcare Safety Network. During
intervention, we implemented the IMA, which included a bundle of infection
prevention practice interventions, education, outcome surveillance, process
surveillance, feedback on VAP rates and consequences, and performance feedback of
process surveillance. Bivariate and multivariate regression analyses were
performed using a logistic regression model to estimate the effect of the
intervention. RESULTS: We recorded 3,940 patients admitted to 14 intensive care
units. At baseline, there were 19.9 VAPs per 1,000 mechanical ventilator (MV)
days-with 2,920 MV-days and 58 VAPs, which was reduced during intervention to 9.4
VAPs per 1,000 MV-days-with 9,261 MV-days and 103 VAPs. This accounted for a 52%
rate reduction (incidence density rate, 0.48; 95% confidence interval, 0.3-0.7; P
.001). CONCLUSIONS: Implementing the IMA was associated with significant
reductions in VAP rates in intensive care units within Argentina.
PMID- 29329918
TI - Trends in incidence of long-term-care facility onset Clostridium difficile
infections in 10 US geographic locations during 2011-2015.
AB - During 2011-2015, the adjusted long-term-care facility onset Clostridium
difficile infection incidence rate in persons aged >=65 years decreased annually
by 17.45% (95% confidence interval, 14.53%-20.43%) across 10 US sites. A
concomitant decline in inpatient fluoroquinolone use and the C difficile epidemic
strain NAP1/027 among persons aged >=65 years may have contributed to the
decrease in long-term-care facility-onset C difficile infection incidence rate.
PMID- 29329919
TI - Comments on risk factors for health care-associated infections: From better
knowledge to better prevention.
PMID- 29329920
TI - Comments on decreased mortality in patients prescribed vancomycin after
implementation of an antimicrobial stewardship program.
PMID- 29329921
TI - Assessment of test methods for evaluating effectiveness of cleaning flexible
endoscopes.
AB - BACKGROUND: Strict adherence to each step of reprocessing is imperative to
removing potentially infectious agents. Multiple methods for verifying proper
reprocessing exist; however, each presents challenges and limitations, and best
practice within the industry has not been established. Our goal was to evaluate
endoscope cleaning verification tests with particular interest in the evaluation
of the manual cleaning step. The results of the cleaning verification tests were
compared with microbial culturing to see if a positive cleaning verification test
would be predictive of microbial growth. METHODS: This study was conducted at 2
high-volume endoscopy units within a multisite health care system. Each of the 90
endoscopes were tested for adenosine triphosphate, protein, microbial growth via
agar plate, and rapid gram-negative culture via assay. The endoscopes were tested
in 3 locations: the instrument channel, control knob, and elevator mechanism.
RESULTS: This analysis showed substantial level of agreement between protein
detection postmanual cleaning and protein detection post-high-level disinfection
at the control head for scopes sampled sequentially. CONCLUSIONS: This study
suggests that if protein is detected postmanual cleaning, there is a significant
likelihood that protein will also be detected post-high-level disinfection. It
also infers that a cleaning verification test is not predictive of microbial
growth.
PMID- 29329922
TI - A multistate investigation of health care-associated Burkholderia cepacia complex
infections related to liquid docusate sodium contamination, January-October 2016.
AB - BACKGROUND: Outbreaks of health care-associated infections (HAIs) caused by
Burkholderia cepacia complex (Bcc) have been associated with medical devices and
water-based products. Water is the most common raw ingredient in nonsterile
liquid drugs, and the significance of organisms recovered from microbiologic
testing during manufacturing is assessed using a risk-based approach. This
incident demonstrates that lapses in manufacturing practices and quality control
of nonsterile liquid drugs can have serious unintended consequences. METHODS: An
epidemiologic and laboratory investigation of clusters of Bcc HAIs that occurred
among critically ill, hospitalized, adult and pediatric patients was performed
between January 1, 2016, and October 31, 2016. RESULTS: One hundred and eight
case patients with Bcc infections at a variety of body sites were identified in
12 states. Two distinct strains of Bcc were obtained from patient clinical
cultures. These strains were found to be indistinguishable or closely related to
2 strains of Bcc obtained from cultures of water used in the production of liquid
docusate, and product that had been released to the market by manufacturer X.
CONCLUSIONS: This investigation highlights the ability of bacteria present in
nonsterile, liquid drugs to cause infections or colonization among susceptible
patients. Prompt reporting and thorough investigation of potentially related
infections may assist public health officials in identifying and removing
contaminated products from the market when lapses in manufacturing occur.
PMID- 29329923
TI - Different protein composition of low-calorie diet differently impacts adipokine
profile irrespective of weight loss in overweight and obese women.
AB - BACKGROUND AND AIMS: High-protein (HP) diets have shown benefits in
cardiometabolic markers such as insulin or triglycerides but the responsible
mechanisms are not known. We aimed to assess the effect of three energy
restricted diets with different protein contents (20%, 27%, and 35%; ~80% coming
from animal source) on plasma adipokine concentration and its association with
changes in cardiometabolic markers. METHODS: Seventy-six women (BMI 32.8 +/-
2.93) were randomized to one of three calorie-reduced diets, with protein, 20%,
27%, or 35%; carbohydrates, 50%, 43%, or 35%; and fat, 30%, for 3 months. Plasma
adipokine (leptin, resistin, adiponectin, and retinol-binding protein 4; RBP4)
levels were assessed. RESULTS: After 3 months, leptin concentration decreased in
all groups without differences among them, while resistin levels remained
unchanged. Adiponectin concentration heterogeneously changed in all groups (P for
trend = 0.165) and resistin concentration did not significantly change. RPB4
significantly decreased by -17.5% (-31.7, -3.22) in 35%-protein diet (P for trend
= 0.024 among diets). Triglycerides improved in women following the 35%-protein
diet regardless of weight loss; RBP4 variation significantly influenced
triglyceride concentration change by 24.9% and 25.9% when comparing 27%- and 35%-
with 20%-protein diet, respectively. CONCLUSIONS: A 35%-protein diet induced a
decrease in RBP4 regardless of weight loss, which was directly associated with
triglyceride concentration improvement. These findings suggest that HP diets
improve the cardiometabolic profile, at least in part, through changes in
adipokine secretion. Whether this beneficial effect of HP diet is due to
improvements in hepatic or adipose tissue functionality should be elucidated.
CLINICAL TRIAL REGISTRATION: The clinical trial has been registered in
ClinicalTrials.gov (Identifier: NCT02160496).
PMID- 29329924
TI - Effects of dark chocolate on endothelial function in patients with non-alcoholic
steatohepatitis.
AB - BACKGROUND AND AIM: Oxidative stress plays a pivotal role in inducing endothelial
dysfunction and progression from simple fatty liver steatosis (FLD) to non
alcoholic steatohepatitis (NASH). Polyphenols could reduce oxidative stress and
restore endothelial function by inhibiting the nicotinamide-adenine-dinucleotide
phosphate (NADPH) oxidase isoform Nox2. The aim of this study was to assess
endothelial function and oxidative stress in a population affected by simple FLD
and NASH. Furthermore, we analysed the effect of high vs low content of cocoa
polyphenols on endothelial function and oxidative stress in patients with NASH.
METHODS: In a cross-sectional study we analysed endothelial function, as assessed
by flow-mediated dilation (FMD), and oxidative stress, as assessed by Nox2
activation, serum isoprostanes and nitric oxide bioavailability (NOx), in
patients with NASH (n = 19), FLD (n = 19) and controls (n = 19). Then, we
performed a randomized, cross-over study in 19 subjects with NASH comparing the
effect of 14-days administration of 40 g of chocolate at high (dark chocolate,
cocoa >85%) versus low content (milk chocolate, cocoa <35%) of polyphenols on FMD
and oxidative stress. Compared to controls, NASH and FLD patients had higher Nox2
activity and isoprostanes levels and lower FMD and NOx, with a significant
gradient between FLD and NASH. The interventional study showed that, compared to
baseline, FMD and NOx increased (from 2.9 +/- 2.4 to 7.2 +/- 3.0% p < 0.001 and
from 15.9 +/- 3.6 to 20.6 +/- 4.9 MUM, p < 0.001, respectively) in subjects given
dark but not in those given milk chocolate. A simple linear regression analysis
showed that Delta (expressed by difference of values between before and after 14
days of chocolate assumption) of FMD was associated with Delta of Nox2 activity
(Rs = -0.323; p = 0.04), serum isoprostanes (Rs: -0.553; p < 0.001) and NOx (Rs:
0.557; p < 0.001). CONCLUSIONS: Cocoa polyphenols improve endothelial function
via Nox2 down-regulation in NASH patients.
PMID- 29329925
TI - Phenotypic and molecular characterization of a serum-free miniature erythroid
differentiation system suitable for high-throughput screening and single-cell
assays.
AB - In vitro erythroid differentiation systems are used to study the mechanisms
underlying normal and abnormal erythropoiesis and to test the effects of various
extracellular factors on erythropoiesis. The use of serum or conditioned medium
in liquid cultures and the seeding of cultures with heterogeneous peripheral
blood mononuclear cells confound the reproducibility of these systems. Newer
erythroid differentiation culture systems have overcome some of these limitations
by using a fully defined, serum-free medium and initiating cultures using
purified CD34+ cells. Although widely used in bulk cultures, these protocols have
not been rigorously tested in high-throughput or single-cell assays. Here, we
describe a serum-free erythroid differentiation system suitable for small-scale
and single-cell experiments. This system generates large numbers of terminally
differentiated erythroid cells of very high purity. Here we have adapted this
culture system to a 96-well format and have developed a protocol to grow
erythroid colonies from single erythroid progenitors in minute culture volumes.
PMID- 29329926
TI - Characterization of Selenoprotein P cDNA of the Antarctic toothfish Dissostichus
mawsoni and its role under cold pressure.
AB - Our previous study using comparative genome analysis revealed a significant gene
copy number gain of Dissostichus mawsoni selenoprotein P (Dm-SEPP) during the
evolutionary radiation of Antarctic notothenioids, suggesting that Dm-SEPP
contribute to this process, but the detailed structure and function of this gene
product remain unclear. In the present study, the Dm-SEPP cDNA was cloned and
characterized. The Dm-SEPP cDNA contains 17 selenocysteines (Sec) encoded by TGA
codons and 2 typical SECIS elements located in the 3'-UTR. Evolutionary analysis
of the Dm-SEPP gene revealed that it's closely related to the SEPP gene of
zebrafish (Danio rerio), showing 51% amino acid similarity. Over-expression of Dm
SEPP could protect mammalian cells under cold pressure, probably via eliminating
ROS. Further study showed an increase of endogenous SEPP in zebrafish ZF4 cells
under cold pressure, and knockdown of SEPP decreased cell viability, accompanied
with increased ROS. Our results suggested a protective role of Dm-SEPP in cold
adaptation in Antarctic notothenioids.
PMID- 29329927
TI - Systems biomarkers in psoriasis: Integrative evaluation of computational and
experimental data at transcript and protein levels.
AB - Psoriasis is a complex autoimmune disease with multiple genes and proteins being
involved in its pathogenesis. Despite the efforts performed to understand
mechanisms of psoriasis pathogenesis and to identify diagnostic and prognostic
targets, disease-specific and effective biomarkers were still not available. This
study is compiled regarding clinical validation of computationally proposed
biomarkers at gene and protein expression levels through qRT-PCR and ELISA
techniques using skin biopsies and blood plasma. We identified several gene and
protein clusters as systems biomarkers and presented the importance of gender
difference in psoriasis. A gene cluster comprising of PI3, IRF9, IFIT1 and NMI
were found as positively correlated and differentially co-expressed for women,
whereas SUB1 gene was also included in this cluster for men. The differential
expressions of IRF9 and NMI in women and SUB1 in men were validated at gene
expression level via qRT-PCR. At protein level, PI3 was abundance in disease
states of both genders, whereas PC4 protein and WIF1 protein were significantly
higher in healthy states than disease states of male group and female group,
respectively. Regarding abundancy of PI3 and WIF1 proteins in women, and PI3 and
PC4 in men may be assumed as systems biomarkers at protein level.
PMID- 29329928
TI - Cloning and characterization of ?6/?5 fatty acyl desaturase (Fad) gene promoter
in the marine teleost Siganus canaliculatus.
AB - The rabbitfish Siganus canaliculatus was the first marine teleost demonstrated to
have the ability of biosynthesizing long-chain polyunsaturated fatty acids (LC
PUFA) from C18 PUFA precursors, and all genes encoding the key enzymes for LC
PUFA biosynthesis have been cloned and functionally characterized, which provides
us a potential model to study the regulatory mechanisms of LC-PUFA biosynthesis
in teleosts. As the primary step to clarify such mechanisms, present research
focused on promoter analysis of gene encoding ?6/?5 fatty acyl desaturase (Fad),
a rate-limiting enzyme catalyzing the first step in the conversion of C18 PUFA to
LC-PUFA. First, 2044 bp promoter sequence was cloned by genome walking, and the
sequence from -456 bp to +51 bp was determined as core promoter by progressive
deletion mutation. Moreover, binding sites of transcription factors (TF) such as
CCAAT enhancer binding protein (C/EBP), nuclear factor 1 (NF-1), stimulatory
protein 1 (Sp1), nuclear factor Y (NF-Y), activated protein 1 (AP1), sterol
regulatory element (SRE), hepatocyte nuclear factor 4alpha (HNF4alpha) and
peroxisome proliferator activated receptor gamma (PPARgamma) were identified in
the core promoter by site-directed mutation and functional assays. Moreover, NF-1
and HNF4alpha were confirmed to interact with the core promoter region by gel
shift assay and mass spectrometry. This is the first report of the promoter
structure of a ?6/?5 Fad in a marine teleost, and a novel discovery of NF-1 and
HNF4alpha binding to the ?6/?5 Fad promoter.
PMID- 29329929
TI - Detoxification genes polymorphisms in SIDS exposed to tobacco smoke.
AB - The best hypothesis to explain Sudden Infant Death Syndrome (SIDS) pathogenesis
is offered by the "triple risk model", which suggests that an interaction of
different variables related to exogenous stressors and infant vulnerability may
lead to the syndrome. Environmental factors are triggers that act during a
particular sensible period, modulated by intrinsic genetic characteristics.
Although literature data show that one of the major SIDS risk factors is smoking
exposure, a specific involvement of molecular components has never been
highlighted. Starting from these observations and considering the role of GSTT1
and GSTM1 genes functional polymorphisms in the detoxification process, we
analyzed GSTM1 and GSTT1 null genotype frequencies in 47 SIDS exposed to tobacco
smoke and 75 healthy individuals. A significant association (p < .0001) between
the GSTM1 null genotype and SIDS exposed to smoke was found. On the contrary, no
association between GSTT1 polymorphism and SIDS was determined. Results indicated
the contribution of the GSTM1 -/- genotype resulting in null detoxification
activity in SIDS cases, and led to a better comprehension of the triple risk
model, highlighting smoking exposure as a real SIDS risk factor on a biochemical
basis.
PMID- 29329930
TI - Ketamine is a good first-line option for severely agitated patients in the
prehospital environment.
PMID- 29329931
TI - Red blood cell distribution width in sepsis.
PMID- 29329933
TI - Combined Hepatic and Pulmonary Metastasectomies From Colorectal Carcinoma. Data
From the Prospective Spanish Registry 2008-2010.
AB - INTRODUCTION: Resection of both liver and lung metastases from colorectal
carcinoma (CRC) is a standard of care in selected patients with oligometastatic
disease. We present here the analysis of the subgroup of patients undergoing
combined surgery from the Spanish Group of Surgery of Pulmonary Metastases (PM)
from Colorectal Carcinoma (GECMP-CCR-SEPAR). METHODS: We analyze characteristics,
survival and prognostic factors of patients undergoing combined resection from
March-2008 to February-2010 and followed-up during at least 3 years, from the
prospective multicenter Spanish Registry. RESULTS: A total of 138 patients from a
whole series of 543 cases from 32 thoracic surgery units underwent both
procedures. Seventy-seven (43.8%) resected liver metastases were synchronic with
colorectal tumor. Median disease specific survival (DSS) from first pulmonary
metastasectomy was 48.9 months, being three and 5-year DSS 65.1% and 41.7%,
respectively. From CRC-surgery median DSS was 97.2 months, with 3 and 5-year DSS
rates of 96.7% and 77%, respectively. Five-year DSS from pulmonary metastasectomy
was 41.7% for patients with combined resection and 52.4% for those without
hepatic involvement (P=.04). Differences disappeared when considering DSS from
colorectal surgery. Carcinoembrionary antigen (CEA) before lung surgery over
10mg/dl and bilateral PM were independent prognostic factors for survival (hazard
ratio 2.4 and 2.5, respectively). CONCLUSIONS: Patients with resection of PM of
CRC with history of resected hepatic metastases presented significantly lower
disease specific survival rates than those undergoing pulmonary metastasectomy
alone. CEA before lung surgery and bilateral PM associated worse prognosis.
PMID- 29329932
TI - Development of the Human Fetal Kidney from Mid to Late Gestation in Male and
Female Infants.
AB - BACKGROUND: During normal human kidney development, nephrogenesis (the formation
of nephrons) is complete by term birth, with the majority of nephrons formed late
in gestation. The aim of this study was to morphologically examine nephrogenesis
in fetal human kidneys from 20 to 41weeks of gestation. METHODS: Kidney samples
were obtained at autopsy from 71 infants that died acutely in utero or within 24h
after birth. Using image analysis, nephrogenic zone width, the number of
glomerular generations, renal corpuscle cross-sectional area and the cellular
composition of glomeruli were examined. Kidneys from female and male infants were
analysed separately. FINDINGS: The number of glomerular generations formed within
the fetal kidneys was directly proportional to gestational age, body weight and
kidney weight, with variability between individuals in the ultimate number of
generations (8 to 12) and in the timing of the cessation of nephrogenesis (still
ongoing at 37weeks gestation in one infant). There was a slight but significant
(r2=0.30, P=0.001) increase in renal corpuscle cross-sectional area from mid
gestation to term in females, but this was not evident in males. The proportions
of podocytes, endothelial and non-epithelial cells within mature glomeruli were
stable throughout gestation. INTERPRETATION: These findings highlight spatial and
temporal variability in nephrogenesis in the developing human kidney, whereas the
relative cellular composition of glomeruli does not appear to be influenced by
gestational age.
PMID- 29329935
TI - Tick-borne pathogen detection: what's new?
AB - Ticks and the pathogens they transmit constitute a growing burden for human and
animal health worldwide. Traditionally, tick-borne pathogen detection has been
carried out using PCR-based methods that rely in known sequences for specific
primers design. This approach matches with the view of a 'single-pathogen'
epidemiology. Recent results, however, have stressed the importance of
coinfections in pathogen ecology and evolution with impact in pathogen
transmission and disease severity. New approaches, including high-throughput
technologies, were then used to detect multiple pathogens, but they all need a
priori information on the pathogens to search. Thus, those approaches are biased,
limited and conceal the complexity of pathogen ecology. Currently, next
generation sequencing (NGS) is applied to tick-borne pathogen detection as well
as to study the interactions between pathogenic and non-pathogenic microorganisms
associated to ticks, the pathobiome. The use of NGS technologies have surfaced
two major points: (i) ticks are associated to complex microbial communities and
(ii) the relation between pathogens and microbiota is bidirectional. Notably, a
new challenge emerges from NGS experiments, data analysis. Discovering
associations among a high number of microorganisms is not trivial and therefore
most current NGS studies report lists of microorganisms without further insights.
An alternative to this is the combination of NGS with analytical tools such as
network analysis to unravel the structure of microbial communities associated to
ticks in different ecosystems.
PMID- 29329936
TI - Child-onset paroxysmal exercise-induced dystonia as the initial manifestation of
hereditary Parkinson's disease.
PMID- 29329934
TI - Application of our understanding of pathogenesis of herpetic stromal keratitis
for novel therapy.
AB - HSV-1 ocular infection can cause herpes stromal keratitis (SK), an
immunopathological lesion. Frequent recurrences can lead to progressive corneal
scaring which can result in vision impairment if left untreated. Currently, the
acute and epithelial forms of SK are usually controlled using anti-viral drugs.
However, chronic forms of SK which are inflammatory in nature, require the
addition of a topical corticosteroid to the anti-viral treatment regimen. In this
review, we highlight the essential events involved in SK pathogenesis which can
be targeted for improved therapy. We also examine some approaches which can be
combined with the current treatments to effectively control SK.
PMID- 29329937
TI - Isolated hemifacial spasm presenting as unilateral, involuntary ear movements.
PMID- 29329938
TI - Pipeline to gene discovery - Analysing familial Parkinsonism in the Queensland
Parkinson's Project.
AB - INTRODUCTION: Family based study designs provide an informative resource to
identify disease-causing mutations. The Queensland Parkinson's Project (QPP) has
been involved in numerous genetic screening studies; however, details of the
families enrolled into the register have not been comprehensively reported. This
article characterises the families enrolled in the QPP and summarises monogenic
forms of hereditary Parkinsonism found in the register. METHOD: The presence of
pathogenic point mutations and copy number variations (CNVs) were, generally,
screened in a sample of over 1000 PD patients from the total of 1725. Whole exome
sequencing (WES) was performed on eighteen probands from multiplex families.
RESULTS: The QPP contains seventeen incidences of confirmed monogenic forms of
PD, including LRRK2 p.G2019S, VPS35 p.D620N, SNCA duplications and PARK2 p.G430D
(hom) & exon 4 deletion (hom). Of these seventeen, five belong to multi-incident
families, while another eight have a family history of at least one other case of
PD. In additional families, WES did not identify known forms of monogenic
Parkinsonism; however, three heterozygous mutations in PARK2, p.R275W, p.Q34fs,
and a 40bp deletion in exon 3 were identified. Of these three mutations, only the
40bp deletion segregated with disease in a dominant inheritance pattern.
CONCLUSION: Eighteen probands have screened negative for known CNVs and mutations
that cause clear monogenic forms of PD. Each family is a candidate for further
genetic analysis to identify genetic variants segregating with disease. The
families enrolled in the QPP provide a useful resource to aid in identifying
novel forms of monogenic PD.
PMID- 29329939
TI - Enhanced mobility of non aqueous phase liquid (NAPL) during drying of wet sand.
AB - Enhanced upward mobility of a non aqueous phase liquid (NAPL) present in wet sand
during natural drying, and in the absence of any external pressure gradients, is
reported for the first time. This mobility was significantly higher than that
expected from capillary rise. Experiments were performed in a glass column with a
small layer of NAPL-saturated sand trapped between two layers of water-saturated
sand. Drying of the wet sand was induced by flow of air across the top surface of
the wet sand. The upward movement of the NAPL, in the direction of water
transport, commenced when the drying effect reached the location of the NAPL and
continued as long as there was significant water evaporation in the vicinity of
NAPL, indicating a clear correlation between the NAPL rise and water evaporation.
The magnitude and the rate of NAPL rise was measured at different water
evaporation rates, different initial locations of the NAPL, different grain size
of the sand and the type of NAPL (on the basis of different NAPL-glass contact
angle, viscosity and density). A positive correlation was observed between
average rate of NAPL rise and the water evaporation while a negative correlation
was obtained between the average NAPL rise rate and the NAPL properties of
contact angle, viscosity and density. There was no significant correlation of
average NAPL rise rate with variation of sand grain size between 0.1 to 0.5mm.
Based on these observations and on previous studies reported in the literature,
two possible mechanisms are hypothesized -a) the effect of the spreading
coefficient resulting in the wetting of NAPL on the water films created and b) a
moving water film due to evaporation that "drags" the NAPL upwards. The NAPL rise
reported in this paper has implications in fate and transport of chemicals in
NAPL contaminated porous media such as soils and exposed dredged sediment
material, which are subjected to varying water saturation levels due to drying
and rewetting.
PMID- 29329940
TI - Cardiovascular Risk Reduction in Persons Living With HIV: Treatment Development,
Feasibility, and Preliminary Results.
AB - Persons living with HIV (PLWH) have elevated risks for cardiovascular disease
(CVD). Our goal was to develop and pilot test a tailored intervention to improve
CVD risk perception and the adoption of heart-healthy behaviors. In-depth
qualitative interviews were conducted with 30 PLWH participants to examine
learning needs and preferences. An intervention manual was developed and tested
in an open pilot with eight participants. Participants were stable on
antiretroviral therapy and were recruited from two urban HIV clinics in the
northeastern United States. Thematic analysis identified five major themes: (a)
tailored structure and design for PLWH, (b) learning needs (specific to HIV), (c)
desire for prompts/reminders (to exercise), (d) importance of participant
resources, and (e) need for personal evaluation and goal setting. Feasibility and
acceptability of the intervention were demonstrated with high session attendance
and treatment satisfaction. Further testing is warranted.
PMID- 29329941
TI - Analysis of refuse-to-file policy for generic drug application in Taiwan.
AB - Generic drugs are accounted for majority of medicinal products. To reduce the
unnecessary review for incomplete dossiers of generic drugs, Taiwanese government
launched a refuse-to-file (RTF) process since 2017. The present study aimed to
examine the outcome of RTF process by analyzing application characteristic, RTF
rate and deficiencies found in the submitted dossiers. Descriptive analyses of
administrative information, chemistry, manufacturing and controls, bioequivalence
study, and comparative dissolution testing were presented during the first 6
months after the implementation of RTF policy. The results showed that the source
of application was likely a determinant to the RTF outcome, i.e., foreign rather
than domestic applications were more liable to be RTF. It is possibly that (i)
RTF applications were mainly due to incomplete dossiers regarding bioequivalence
study and comparative dissolution testing, and (ii) the studies (bioequivalence
and dissolution) of domestic applications conducted locally are exempted from the
RTF process because they are allowed to submit for review before generic drug
applications. Finally, the dossier integrity appeared not improved during the
period of analysis as the number of RTF did not reduce by month. Results of the
present study may help pharmaceutical industry to improve the dossiers' quality
by fixing the deficiencies of generic drug submission.
PMID- 29329942
TI - Variational neuroethology: Answering further questions: Reply to comments on
"Answering Schrodinger's question: A free-energy formulation".
PMID- 29329943
TI - Experience versus diagnosis as the appropriate basis for assessment of
depression: A reply to the commentary from Kirmayer et al. (2017).
PMID- 29329944
TI - Use of SuperARMS EGFR Mutation Detection Kit to Detect EGFR in Plasma Cell-free
DNA of Patients With Lung Adenocarcinoma.
AB - BACKGROUND: The SuperARMS EGFR Mutation Detection Kit (SuperARMS) is highly
selective and sensitive and able to detect 41 of the most common somatic
mutations in exons 18 to 21 of the epidermal growth factor receptor gene (EGFR).
It allows for the detection of 0.2% to 0.8% mutant DNA in a background of 99.8%
to 99.2% normal DNA. The present study assessed the performance of SuperARMS in
detecting EGFR mutations in cell-free DNA (cfDNA) samples derived from plasma in
patients with advanced lung adenocarcinoma. MATERIALS AND METHODS: A total of 180
patients with advanced clinical stage lung adenocarcinoma were retrospectively
registered. The concordance between the EGFR mutations detected by SuperARMS and
ARMS (AmoyDx EGFR 29 Mutations Detection Kit) was analyzed. RESULTS: Of the 180
samples, 57 (31.7%) were positive for EGFR mutations using SuperARMS, with 38
(21.1%) positive using ARMS. For the entire cohort, the positive, negative, and
overall concordance rates were 97.3% (95% confidence interval [CI], 86.2%-99.5%),
85.3% (95% CI, 78.6%-90.2%), and 87.8% (95% CI, 82.2%-91.8%), respectively. The
kappa value was 0.69 (95% CI, 0.57-0.81). For the 61 treatment-naive patients and
119 previously treated patients, the kappa values were 0.59 (95% CI, 0.37-0.79)
and 0.74 (95% CI, 0.60-0.87), respectively. SuperARMS identified 9 samples
harboring the T790M mutation; of these, only 1 (11.1%) was detected using ARMS.
CONCLUSION: SuperARMS is a promising plasma-based assay for EGFR mutations,
including T790M. It might be useful in advanced-stage lung adenocarcinoma
patients whose tissue biopsy samples are insufficient for a traditional
diagnostic EGFR assay or for patients with a poor performance status.
PMID- 29329945
TI - Model of acetic acid-affected growth and poly(3-hydroxybutyrate) production by
Cupriavidus necator DSM 545.
AB - Acetic acid, a potential growth inhibitor, commonly occurs in lignocellulosic
hydrolysates. The growth of Cupriavidus necator DSM 545 and production of poly(3
hydroxybutyrate) (PHB) by this bacterium in a glucose-based medium supplemented
with various initial concentrations of acetic acid are reported. The bacterium
could use both glucose and acetic acid to grow and produce PHB, but acetic acid
inhibited growth once its initial concentration exceeded 0.5 g/L. As acetic acid
is an unavoidable contaminant in hydrolysates used as sugar sources in commercial
fermentations, a mathematical model was developed to describe its impact on
growth and the production of PHB. The model was shown to satisfactorily apply to
growth and PHB production data obtained in media made with acetic-acid-containing
hydrolysates of Napier grass and oil palm trunk as carbon substrates.
PMID- 29329946
TI - A primer on caspase mechanisms.
AB - Caspases belong to a diverse clan of proteolytic enzymes known as clan CD with
highly disparate functions in cell signaling. The caspase members of this clan
are only found in animals, and most of them orchestrate the demise of cells by
the highly distinct regulated cell death phenotypes known as apoptosis and
pyroptosis. This review looks at the mechanistic distinctions between the
activity and activation mechanisms of mammalian caspases compared to other
members of clan CD. We also compare and contrast the role of different caspase
family members that program anti-inflammatory and pro-inflammatory cell death
pathways.
PMID- 29329947
TI - [Pseudoexfoliation syndrome and pseudoexfoliation glaucoma].
AB - Pseudoexfoliation syndrome is an age-related systemic disease that mainly affects
the anterior structures of the eye. Despite a worldwide distribution, reported
incidence and prevalence of this syndrome vary widely between ethnicities and
geographical areas. The exfoliative material is composed mainly of abnormal cross
linked fibrils that accumulate progressively in some organs such as the heart,
blood vessels, lungs or meninges, and particularly in the anterior structures of
the eye. The exact pathophysiological process still remains unclear but the
association of genetic and environmental factors are thought to play a role in
the development and progressive extracellular accumulation of exfoliative
material. Hence, LOXL1 gene polymorphisms, responsible for metabolism of some
components of elastic fibers and extracellular matrix, and increased natural
exposure to ambient ultraviolet or caffeine consumption have been associated with
pseudoexfoliation syndrome. Ophthalmological manifestations are commonly
bilateral with an asymmetric presentation and can lead to severe visual
impairment and blindness more frequently than in the general population, mainly
related to glaucoma and cataract. Pseudoexfoliation glaucoma is a major
complication of pseudoexfoliation syndrome and represents the main cause of
identifiable glaucoma worldwide. Visual field progression is more rapid than that
observed in primary open angle glaucoma, and filtering surgery is more frequently
required. Nuclear cataract is more frequent and occurs earlier than in the
general population. Owing to poorer pupil dilation and increased zonular
instability, cataract surgery with pseudoexfoliation is associated with a 5- to
10-fold increase in surgical complications compared to cataract surgery without
pseudoexfoliation. Some specific treatments targeting production, formation or
accumulation of exfoliative material could improve the prognosis of this
syndrome.
PMID- 29329949
TI - Running Out of Success in HF Therapy ?
PMID- 29329948
TI - NKp46 Receptor-Mediated Interferon-gamma Production by Natural Killer Cells
Increases Fibronectin 1 to Alter Tumor Architecture and Control Metastasis.
AB - Natural killer (NK) cells are innate lymphoid cells, and their presence within
human tumors correlates with better prognosis. However, the mechanisms by which
NK cells control tumors in vivo are unclear. Here, we used reflectance confocal
microscopy (RCM) imaging in humans and in mice to visualize tumor architecture in
vivo. We demonstrated that signaling via the NK cell receptor NKp46 (human) and
Ncr1 (mouse) induced interferon-gamma (IFN-gamma) secretion from intratumoral NK
cells. NKp46- and Ncr1-mediated IFN-gamma production led to the increased
expression of the extracellular matrix protein fibronectin 1 (FN1) in the tumors,
which altered primary tumor architecture and resulted in decreased metastases
formation. Injection of IFN-gamma into tumor-bearing mice or transgenic
overexpression of Ncr1 in NK cells in mice resulted in decreased metastasis
formation. Thus, we have defined a mechanism of NK cell-mediated control of
metastases in vivo that may help develop NK cell-dependent cancer therapies.
PMID- 29329950
TI - Dual Vasopressin V1a/V2 Antagonism: The Next Step in Neurohormonal Modulation in
Patients With Heart Failure?
AB - Stimulation of the V1a receptor for arginine vasopressin produces myocardial and
vascular effects similar to those of angiotensin II while stimulation of the V2
receptor causes fluid retention. There are no data with sustained blockade of the
V1a receptor while single-dose experiments suggest benefit. Acute and chronic
administration of selective V2 receptor antagonists reliably relieves dyspnea and
produces diuresis without adverse effects on renal function or neurohormonal
stimulation, either as adjunctive or alternative therapy to loop diuretics, but
has not been shown to improve outcomes as adjunctive therapy. Combined antagonism
has been tried only in single-dose studies in stable patients or over the short
term in acute heart failure, with encouraging results. Based on the both the
pathophysiologic rationale for additional neurohormonal blockade and these
results, chronically blocking both receptors, particularly in more congested
patients, may offer significant benefit either as adjunctive or alternative
therapy to standard diuretics.
PMID- 29329951
TI - Medical and health risks associated with communicable diseases of Rohingya
refugees in Bangladesh 2017.
AB - Complex emergencies remain major threats to human well-being in the 21st century.
More than 300000 Rohingya people from Myanmar, one of the most forgotten
minorities globally, have fled to neighboring countries over the past decades. In
the recent crisis, the sudden influx of Rohingya people over a 3-month period
almost tripled the accumulated displaced population in Bangladesh. Using the
Rohingya people in Bangladesh as a case context, this perspective article
synthesizes evidence in the published literature regarding the possible key
health risks associated with the five main health and survival supporting
domains, namely water and sanitation, food and nutrition, shelter and non-food
items, access to health services, and information, for the displaced living in
camp settlements in Asia.
PMID- 29329952
TI - Molecular characterization and expression of complement factor I in Pelteobagrus
vachellii during Aeromonas hydrophila infection.
AB - Complement factor I (CFI) is a novel regulatory serine protease that plays an
important role in resistance to pathogen infection. In this study, the CFI gene
of Pelteobagrus vachellii (Pv-CFI) was sequenced and characterized. The full
length cDNA of 2320 bp includes a 155 bp 5'-untranslated region (UTR), a 164 bp
3'-UTR, and a 2001 bp open reading frame (ORF) encoding a 667 amino acids.
Multiple sequence alignment revealed five highly conserved domains with a typical
modular architecture and identical active sites in vertebrates, indicating a
conserved function. Pv-CFI mRNA was constitutively expressed in all examined
tissues and most abundant in liver. During infection with Aeromonas hydrophila,
Pv-CFI mRNA expression was significantly up-regulated in liver at 3-24 h, spleen
at 3-48 h and head kidney at 3-48 h. The results suggest Pv-CFI plays an
important role in resistance to pathogenic bacteria in P. vachellii.
PMID- 29329953
TI - Canine macrophages can like human macrophages be in vitro activated toward the
M2a subtype relevant in allergy.
AB - The M2a subtype of macrophages plays an important role in human immunoglobulin E
(IgE-mediated allergies) and other Th2 type immune reactions. In contrast, very
little is known about these cells in the dog. Here we describe an in vitro method
to activate canine histiocytic DH82 cells and primary canine monocyte-derived
macrophages (MDMs) toward the M2a macrophages using human cytokines. For a side
by-side comparison, we compared the canine cells to human MDMs, and the human
monocytic cell line U937 activated towards M1 and M2a cells on the cellular and
molecular level. In analogy to activated human M2a cells, canine M2a,
differentiated from both DH82 and MDMs, showed an increase in CD206 surface
receptor expression compared to M1. Interestingly, canine M2a, but not M1 derived
from MDM, upregulated the high-affinity IgE receptor (FcepsilonRI). Transcription
levels of M2a-associated genes (IL10, CCL22, TGFbeta, CD163) showed a diverse
pattern between the human and dog species, whereas M1 genes (IDO1, CXCL11, IL6,
TNF-alpha) were similarly upregulated in canine and human M1 cells (cell lines
and MDMs). We suggest that our novel in vitro method will be suitable in
comparative allergology studies focussing on macrophages.
PMID- 29329954
TI - Comparative myology of the ankle of Leopardus wiedii and L. geoffroyi (Carnivora:
Felidae): functional consistency with osteology, locomotor habits and hunting in
captivity.
AB - Leopardus wiedii (margay) is the only arboreal Neotropical felid able to climb
head-first down trees, due to its ability to rotate its tarsal joint 180 degrees
. A closely related, similar-sized species, L. geoffroyi (Geoffroy's cat)
exhibits more typical terrestrial habits and lacks the arboreal capabilities of
L. wiedii. There is osteological evidence that supports a mechanical
specialization of L. wiedii's tarsal joint for inversion, but there have been no
studies on the myology of this specialization. Based on comparative gross-anatomy
dissections of zeugo- and autopodial muscles related to the ankle joint of one
margay specimen and two Geoffroys cats, we identified myological specializations
of L. wiedii that support its arboreal abilities. In addition, we documented both
species hunting the same prey (domestic pigeon Columba livia, Aves: Columbidae)
in captivity, to complement. We report differences in the origin, insertion and
belly in 8 of the 10 dissected muscles. At least 3 of these interspecific
variations can be associated with strengthening of the main muscles that command
inversion/eversion movements of the tarsal joint and support the body weight in
the head-down climbing position typical of L. wiedii. Frame-by-frame video
reconstructions depict the sequence of movements in these species while hunting
and highlight the advantages of the arboreal abilities of L. wiedii.
PMID- 29329955
TI - Longitudinal predictors of early language in infants with Down syndrome: A
preliminary study.
AB - PURPOSE: Children with Down syndrome (DS) typically have marked delays in
language development relative to their general cognitive development, with
particular difficulties in expressive compared to receptive language. Although
early social communication skills, including gestures and joint attention, have
been shown to be related to later language outcomes in DS, knowledge is limited
as to whether these factors exclusively predict outcomes, or whether other
factors (e.g. perceptual and non-verbal skills) are involved. This study
addressed this question. METHOD: Longitudinal data for a group of infants with DS
(n = 14) and a group of typically-developing (TD) infants (n = 35) were collected
on measures that have been shown to predict language in TD infants and/or those
with developmental delays. These included: non-verbal mental ability, speech
segmentation skills, and early social communication skills (initiating and
responding to joint attention, initiating behavioural requests). RESULTS: Linear
regression analyses showed that speech segmentation and initiating joint
attention were the strongest predictors of later language in the TD group,
whereas non-verbal mental ability and responding to joint attention were the
strongest predictors of later language for infants with DS. CONCLUSIONS: Speech
segmentation ability may not determine language outcomes in DS, and language
acquisition may be more constrained by social communication and general cognitive
skills.
PMID- 29329956
TI - Herd immunity: hyperimmune globulins for the 21st century.
PMID- 29329957
TI - Safety and tolerability of a novel, polyclonal human anti-MERS coronavirus
antibody produced from transchromosomic cattle: a phase 1 randomised, double
blind, single-dose-escalation study.
AB - BACKGROUND: Middle East respiratory syndrome (MERS) is a severe respiratory
illness with an overall mortality of 35%. There is no licensed or proven
treatment. Passive immunotherapy approaches are being developed to prevent and
treat several human medical conditions where alternative therapeutic options are
absent. We report the safety of a fully human polyclonal IgG antibody (SAB-301)
produced from the hyperimmune plasma of transchromosomic cattle immunised with a
MERS coronavirus vaccine. METHODS: We did a phase 1 double-blind, placebo
controlled, single-dose escalation trial at the National Institutes of Health
Clinical Center. We recruited healthy participants aged 18-60 years who had
normal laboratory parameters at enrolment, a body-mass index of 19-32 kg/m2, and
a creatinine clearance of 70 mL/min or more, and who did not have any chronic
medical problems that required daily oral medications, a positive rheumatoid
factor (>=15 IU/mL), IgA deficiency (<7 mg/dL), or history of allergy to
intravenous immunoglobulin or human blood products. Participants were randomly
assigned by a computer-generated table, made by a masked pharmacist, to one of
six cohorts (containing between three and ten participants each). Cohorts 1 and 2
had three participants, randomly assigned 2:1 to receive active drug SAB-301
versus normal saline placebo; cohorts 3 and 4 had six participants randomised
2:1; and cohorts 5 and 6 had ten participants, randomised 4:1. Participants
received 1 mg/kg, 2.5 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg, or 50 mg/kg of SAB-301,
or equivalent volume placebo (saline control), on day 0, and were followed up by
clinical, laboratory, and pharmacokinetic assessments on days 1, 3, 7, 21, 42,
and 90. The primary outcome was safety, and immunogenicity was a secondary
outcome. We analysed the intention-to-treat population. This trial is registered
with ClinicalTrials.gov, number NCT02788188. FINDINGS: Between June 2, 2016, and
Jan 4, 2017, we screened 43 participants, of whom 38 were eligible and randomly
assigned to receive SAB-301 (n=28) or placebo (n=10). 97 adverse events were
reported: 64 adverse events occurred in 23 (82%) of 28 participants receiving SAB
301 (mean 2.3 adverse events per participant). 33 adverse events occurred in all
ten participants receiving placebo (mean 3.3 adverse events per participant). The
most common adverse events were headache (n=6 [21%] in participants who received
SAB-301 and n=2 [20%] in those receiving placebo), albuminuria (n=5 [18%] vs n=2
[20%]), myalgia (n=3 [11%] vs n=1 [10%]), increased creatine kinase (n=3 [11%] vs
1 [10%]), and common cold (n=3 [11%] vs n=2 [20%]). There was one serious adverse
event (hospital admission for suicide attempt) in one participant who received 50
mg/kg of SAB-301. The area under the concentration-time curve (AUC) in the 50
mg/kg dose (27 498 MUg * days per mL) is comparable to the AUC that was
associated with efficacy in a preclinical model. INTERPRETATION: Single infusions
of SAB-301 up to 50 mg/kg appear to be safe and well tolerated in healthy
participants. Human immunoglobulin derived from transchromosomic cattle could
offer a new platform technology to produce fully human polyclonal IgG antibodies
for other medical conditions. FUNDING: National Institute of Allergy and
Infectious Diseases, National Institutes of Health, and Biomedical Advanced
Research and Development Authority.
PMID- 29329958
TI - Contact tracing for the control of infectious disease epidemics: Chronic Wasting
Disease in deer farms.
AB - Contact tracing is a crucial component of the control of many infectious
diseases, but is an arduous and time consuming process. Procedures that increase
the efficiency of contact tracing increase the chance that effective controls can
be implemented sooner and thus reduce the magnitude of the epidemic. We
illustrate a procedure using Graph Theory in the context of infectious disease
epidemics of farmed animals in which the epidemics are driven mainly by the
shipment of animals between farms. Specifically, we created a directed graph of
the recorded shipments of deer between deer farms in Pennsylvania over a
timeframe and asked how the properties of the graph could be exploited to make
contact tracing more efficient should Chronic Wasting Disease (a prion disease of
deer) be discovered in one of the farms. We show that the presence of a large
strongly connected component in the graph has a significant impact on the number
of contacts that can arise.
PMID- 29329959
TI - miR-21 suppression prevents cardiac alterations induced by d-galactose and
doxorubicin.
AB - d-galactose (d-gal)-induced cardiac alterations and Doxorubicin (Dox)-induced
cardiomyocyte senescence are commonly used models to study cardiac aging.
Accumulating evidence has suggested that microRNAs (miRNAs, miRs) are critically
involved in the regulation of cellular and organismal aging and age-related
diseases. However, little has been revealed about the roles of miRNAs in cardiac
alterations induced by d-gal and Dox. In this study, we used miRNA arrays to
investigate the dysregulated miRNAs in heart samples from 15month-old versus
2month-old male C57BL/6 mice and further validated them in d-gal-induced pseudo
aging mouse model and Dox-induced cardiomyocyte senescence in vitro model. We
confirmed a significant increase of miR-21 in all these models by quantitative
reverse transcription polymerase chain reactions. We further demonstrated that
miR-21 was able to promote Dox-induced cardiomyocyte senescence whereas
suppression of miR-21 could prevent that, as determined by percentage of beta-gal
positive cells and gene markers of aging. Phosphatase and tensin homolog (PTEN)
was identified as a target gene of miR-21, mediating its effect in increasing
cardiomyocyte senescence. Finally, we found that miR-21 knockout mice were
resistant to d-gal-induced alterations in aging-markers and cardiac function.
Collectively, this study provides direct evidence that inhibition of miR-21 is
protective against d-gal-induced cardiac alterations and Dox-induced
cardiomyocyte senescence via targeting PTEN. Inhibition of miR-21 might be a
novel strategy to combat cardiac aging.
PMID- 29329960
TI - The Future of LGBT Cancer Care: Practice and Research Implications.
AB - OBJECTIVES: To synthesize state of the knowledge collected in this volume and
propose future directions for lesbian, gay, bisexual and transgender (LGBT)
cancer practice, education, research, and advocacy. DATA SOURCES: Current and
extant literature. CONCLUSION: Health care disparities that are known but not yet
fully elucidated in the LGBT population carry into the cancer arena.
Substantially more effort is required in the domains of patient care, nursing
practice, nursing and patient-facing services provider education, patient
education, nursing and interprofessional research, governmental commitment,
professional organization action, and patient advocacy. IMPLICATIONS FOR NURSING
PRACTICE: Professional nurses are committed to the uniqueness of each individual
and respect and value the health and well-being of each individual. To that
commitment, oncology nurses are positioned to advance the research in the field,
which will help to clarify the issues and concerns related to LGBT cancer,
address the health care inequities in this important population, and lead to
improved outcomes for all.
PMID- 29329961
TI - [Personalised health services: Suggestions for their effective implementation].
AB - A strategy of customisation, and its subsequent practical implementation as part
of personalised treatment pathways, is an appropriate approach to increase
benefits for patients and to strengthen the competitive position of the provider
of health services. This requires restructuring and/or reorganising measures to
enable variants within the treatment pathway as a value creation process to be
adapted to each individual patient and his illness, living conditions and
preferences. This 'mass customisation' approach allows us to achieve the
objective of a constructive interconnection of customisation and standardisation
of health services. Major, rapid progress in information and communication
technology plays a key part in this process. Focused design tools for mass
customisation are the integration of patients into the service delivery process
and the modularisation of processes and organisation. By taking into account the
specificities of health services as a confidence good these design tools are
featured and supported by operational and organisational tools in order to
develop variants. This approach allows for high-quality health services that are
perfectly tailored to individual patients' needs and, at the same time, delivered
in an economic way. On this basis, customised approaches for personalised health
diagnosis and therapy provide patient-focused health services that manage to
apply the concept of value-based healthcare in a sophisticated and effective
form.
PMID- 29329962
TI - Reported contraceptive use in the month of becoming pregnant among U.S. abortion
patients in 2000 and 2014.
AB - OBJECTIVES: The objective was to determine whether types of contraceptive methods
used by abortion patients in the month they became pregnant changed between 2000
and 2014. STUDY DESIGN: We used secondary data from the 2000 (n=10,015) and 2014
(8177) Abortion Patient Surveys. Patients were asked which contraceptive methods
they had last used and when they had stopped or if they were still using them.
The main outcome variable was type of contraceptive method used in the month the
pregnancy began. We used bivariate logistic regressions to assess changes in the
demographic and contraceptive use profiles of abortion patients. RESULTS: In both
years, slightly more than half of patients reported that they had used a
contraceptive method in the month they became pregnant, though the decline from
54% in 2000 to 51% in 2014 was statistically significant (p=.011). The methods
most commonly reported to have been used in the month the pregnancy began were
condoms (28% and 24% in 2000 and 2014, p<.001) followed by the pill (14% and 13%,
p=.12). There was a statistically significant increase in the proportion of
abortion patients who reported using long-acting reversible methods in the month
they got pregnant (0.1% in 2000 vs. 1% in 2014, p<.001), and the estimated number
of abortions attributed to these users was greater in 2014 than in 2000 (9500 vs.
1800). CONCLUSIONS: Contraceptive use patterns of abortion patients were similar
in both time periods, and changes in method use mirrored changes in contraceptive
use among the larger population of women. IMPLICATIONS: Postabortion
contraception counseling has the potential to help nonusers find methods that
meet their preferences and to help women better use their current methods.
PMID- 29329963
TI - Switch to Ticagrelor in critical limb ischemia antiplatelet study (STT-CLIPS).
AB - OBJECTIVE: To investigate platelet reactivity in patients with critical limb
ischemia (CLI) after switching from clopidogrel to ticagrelor. BACKGROUND: High
on-treatment platelet reactivity (HPR) is highly prevalent in patients with CLI
treated with clopidogrel. The effect of ticagrelor in patients with CLI is not
known, however. METHODS: We performed P2Y12 platelet receptor inhibition studies
(VASP and VerifyNow) in 50 patients with CLI. Tests were performed before and 6+/
1h after daily 75mg clopidogrel dose. Patients were then switched to ticagrelor
90mg twice daily for two weeks and platelet assays repeated. Patients were
divided based on VerifyNow P2Y12 reaction units (PRU). Group 1: HPR defined as
PRU >=208 and Group 2: Appropriate platelet inhibition (API), PRU <208. RESULTS:
After two weeks of uninterrupted antiplatelet therapy, mean PRU results were 173
PRU and 71 PRU at baseline (p<0.0001) and 140 PRU and 63 PRU after 6h (p<0.0001)
for clopidogrel and ticagrelor, respectively. Before daily clopidogrel dose, 36%
of patients (n=18) demonstrated HPR and after 6h, 30% (n=15). One patient (2%)
had HPR on ticagrelor. Ninety-four percent of patients with HPR on clopidogrel
demonstrated appropriate platelet inhibition after switching to ticagrelor and
all patients with API on clopidogrel remained with API after switching to
ticagrelor. Six hours after daily dosing, VASP-PRI >50% was found in 42% of
clopidogrel and 2% of ticagrelor treated patients. CONCLUSIONS: Among patients
with CLI, ticagrelor achieved greater platelet inhibition than clopidogrel during
maintenance treatment and at 6h after daily dosing. High on-treatment platelet
reactivity to clopidogrel in patients with CLI can be overcome by switching to
ticagrelor.
PMID- 29329964
TI - Is quality of registry treatment data related to registrar experience and
workload? A study of Taiwan cancer registry data.
AB - BACKGROUND: Although cancer treatment information has been collected through the
Cancer Registry system in Taiwan for more than 10 years, the accuracy of such
data has never been evaluated. This study examined the accuracy rate between
registrar experience and on-site chart review for the first course of cancer
treatment. METHODS: In this retrospective chart review study, 392 randomly
selected medical records from 14 hospitals were re-abstracted by experienced
abstractors. The kappa coefficients of accuracy for the abstracting data were
calculated against the gold standard. Correlations between registrar background
and workload were then identified through regression analysis. RESULTS: Regarding
surgery type, low accuracy rates were noted for gastric cancer (84.0%), oral
cavity cancer (84.6%), and bladder cancer (88.9%). For chemotherapy, low accuracy
rates were observed for hematopoietic diseases (81.3%) and esophageal cancer
(88.0%). For radiotherapy, low accuracy rates were noted for esophageal cancer
(80.0%), cervical cancer (81.8%), and lymphoma (85.7%). When stratifying by
surgery type after adjustment for hospital caseload, a high accuracy rate was
found for cancer registrars who had progressed from basic to advanced licenses
within 5 years of graduating. CONCLUSION: The accuracy rate for the first course
of cancer treatment was affected by the cancer type and the experience of cancer
registrars, but it was not affected by the workload of cancer registrars. We
recommend that cancer registrars with basic licenses upgrade to advanced licenses
as soon as possible. Medical record collaboration should establish documentation
for checklist of radiotherapy and surgical operation records.
PMID- 29329965
TI - Migration of inferior vena cava filter during the surgery of tibial shaft
fracture: A case report.
PMID- 29329966
TI - [Overview of the knowledge and attitudes of physicians in Brazzaville on
obstructive sleep apnea syndrome].
AB - INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is the leading sleep
related breathing disorder. Its complications and its repercussions on the
quality of life of patients make the OSAS a real public health problem. The
objective of this study is to both asses physicians knowledge of OSAS and
describe their attitudes towards suspect subjects in Brazzaville. MATERIAL AND
METHOD: This was a cross-sectional study of 230 doctors practicing in various
hospitals in the city of Brazzaville. The data collection was done by a self
questionnaire developed after a bibliographic analysis on the OSAS. The
questionnaire was completed without recourse to a source of information. RESULTS:
Our sample consisted of 141 (70.50%) general practitioners and 59 (29.50%)
specialist physicians. The average of the knowledge score was 9.34 points+/-3.03
points. The general level of physician knowledge about SAS was good in 2% of
cases, average in 44% of cases and low in 54% of cases. The level of knowledge
was related to the number of times the OSAS diagnosis was mentioned by the
physician in his practice (P<0.001), to the doctor's grade (P=0.003); to his
university of origin and to the quantity of sources of information. When faced
with suspects OSAS subjects, the doctor, the doctor directed the patient in 62%
of the cases in ENT and in 49% in the pulmonology. CONCLUSION: The knowledge of
the doctors on the OSAS are weak; this results in poor management of this
pathology in the Congo.
PMID- 29329967
TI - [Prevalence of HIV-Tuberculosis co-infection and HIV impact on patients with
tuberculosis in the Lubumbashi Health Zone from 2014 to 2015].
AB - BACKGROUND: Tuberculosis and HIV/AIDS are a dangerous couple in sub-Saharan
Africa. The aim of this paper is to evaluate the prevalence of the co-infection
tuberculosis/HIV/AIDS and its impact on issues of tuberculosis patients treated
in Lubumbashi Heath Zone (LHZ). MATERIALS AND METHODS: A retrospective and
transversal study was conducted through the analysis of tuberculosis patients'
data admitted in the tuberculosis Health Centers for Diagnosis and treatment
(HCDT) in the LHZ from January 2014 to December 2015. TB-HIV co-infection cases
will be identified and the outcome will be analyzed. RESULTS: Data of 1368
patients were noted from three HCDT of the TB of the Lubumbashi ZS and among them
334 cases of co-infections were recorded. The most incriminated age range is 40
50 years. The mean of age of our patients is 32.84+/-15.32 years and the
man/women sex ratio is 1.70. The most predominant clinical tuberculosis form is
the extra pulmonary [EPT (52.70 %)]. Among co-infected patients, the predominant
form is pulmonary (TPM-). Out of the 51 cases of deaths recorded, 23 (45.10 %)
also had HIV while 28 (54.90 %) were HIV-negative. There was an increase of 11.6
% in TB-HIV/AIDS co-infection from 2014 to 2015. CONCLUSION: TB-HIV/AIDS co
infection is a reality in the LHZ, especially in patients with negative bacterial
TB (TPM-) and we have to pay a particular attention on the impact of HIV on the
death of tuberculosis patients.
PMID- 29329968
TI - Reexamining unconscious response priming: A liminal-prime paradigm.
AB - Research on the limits of unconscious processing typically relies on the
subliminal-prime paradigm. However, this paradigm is limited in the issues it can
address. Here, we examined the implications of using the liminal-prime paradigm,
which allows comparing unconscious and conscious priming with constant
stimulation. We adapted an iconic demonstration of unconscious response priming
to the liminal-prime paradigm. On the one hand, temporal attention allocated to
the prime and its relevance to the task increased the magnitude of response
priming. On the other hand, the longer RTs associated with the dual task inherent
to the paradigm resulted in response priming being underestimated, because
unconscious priming effects were shorter-lived than conscious-priming effects.
Nevertheless, when the impact of long RTs was alleviated by considering the
fastest trials or by imposing a response deadline, conscious response priming
remained considerably larger than unconscious response priming. These findings
suggest that conscious perception strongly modulates response priming.
PMID- 29329969
TI - Inattentional blindness on the full-attention trial: Are we throwing out the baby
with the bathwater?
AB - When attention is otherwise engaged, observers may experience inattentional
blindness, failing to notice objects or events that are presented in plain sight.
In an inattentional blindness experiment, an unexpectedstimulus ispresented
alongside primary-task stimuli, and its detection is probed. We evaluate a
criterion that is commonly used to exclude observers from the data analysis. On
the final experimental trial, observers do not perform the primary task, but
instead look for anything new. Observers who fail to report the unexpected
stimulus on thisfull-attention trialare excluded. On the basis of 4 hypothetical
experiments and a review of 128 actual experiments from the literature, we
demonstrate some potentially problematic consequences of implementing the full
attention-trial exclusion criterion. Excluded observers may cluster in
experimental conditions and the exclusion criterion may lead researchers to
understate the pervasiveness of inattentional blindness. It may even render
usblindto inattentional blindness on the full-attention trial.
PMID- 29329970
TI - A prospective study on the association of sleep duration with grip strength among
middle-aged and older Chinese.
AB - BACKGROUND: Longitudinal studies on sleep duration and grip strength decline are
limited. This study aimed to evaluate the associations of baseline sleep duration
with follow-up grip strength and grip strength changeover time among a large
sample of middle-aged and older Chinese. METHODS: Data from China Health and
Retirement Longitudinal Study, CHARLS (2011-2015), were analyzed. Hand grip
strength was measured by dynamometers twice with 4 years interval. Baseline self
reported nighttime sleep duration was collected by questionnaire. Basic
demographics, life habits and health status were considered as potential
confounders. Multivariate linear regression models with quadratic function and
mixed-effects regression models were fitted. RESULTS: Inverted U-shaped
associations occurred between baseline sleep duration and follow-up grip strength
for both males (betalinear = 1.011, plinear = 0.002; betaquadratic = -0.061,
pquadratic = 0.014) and females (betalinear = 0.605, plinear = 0.005,
betaquadratic = -0.041, pquadratic = 0.019). Compared to the sleep duration of 7
h, significant interactions of <5 hours-by-time (gamma= - 0.966 with SEE = 0.442,
p = .029) in males as well as 5-7 hours-by-time (gamma= - 0.717 with SEE = 0.294,
p = .015), 7-9 hours-by-time (gamma= - 0.632 with SEE = 0.311, p = .042) and >9
hours-by-time (gamma= - 1.567 with SEE = 0.560, p = .005) in females were found.
CONCLUSION: For both males and females, compared to the intermediate sleep
duration, shorter or longer sleep may predict the weaker follow-up grip strength
and the faster rate of hand grip strength decline over time.
PMID- 29329971
TI - Muscle quality is associated with dynamic balance, fear of falling, and falls in
older women.
PMID- 29329972
TI - Enhanced production of lactate-based polyesters in Escherichia coli from a
mixture of glucose and xylose by Mlc-mediated catabolite derepression.
AB - Lignocellulose-utilizing biorefinery is a promising strategy for the sustainable
production of value-added products such as bio-based polymers. Simultaneous
consumption of glucose and xylose in Escherichia coli was achieved by
overexpression of the gene encoding Mlc, a multiple regulator of glucose and
xylose uptake. This catabolite derepression gave the enhancement in the
production of poly (15 mol% lactate-co-3-hydroxybutyrate), up to 65% from 50%
(wild-type strain) in the cellular contents, of the Mlc-overexpressing strain of
E. coli on a mixture of glucose and xylose as carbon sources. Microscopic
analysis indicated that the Mlc-overexpressing strain showed the enlargement of
cell volume in the presence and absence of polymer production, consequently
making an expanded volumetric space available for enhanced polymer accumulation.
The enhanced polymer production by the catabolite derepression was also
reproducible using the biomass, Miscanthus*giganteus (hybrid Miscanthus), which
was cultivated in the farm of Hokkaido University.
PMID- 29329974
TI - Bariatric surgery: many benefits, but emerging risks.
PMID- 29329973
TI - Altered gene expression in tree shrew retina and retinal pigment epithelium
produced by short periods of minus-lens wear.
AB - Hyperopic refractive error is detected by retinal neurons, which generate GO
signals through a direct emmetropization signaling cascade: retinal pigment
epithelium (RPE) into choroid and then into sclera, thereby increasing axial
elongation. To examine signaling early in this cascade, we measured gene
expression in the retina and RPE after short exposure to hyperopia produced by
minus-lens wear. Gene expression in each tissue was compared with gene expression
in combined retina + RPE. Starting 24 days after normal eye opening, three groups
of juvenile tree shrews (n = 7 each) wore a monocular -5 D lens. The untreated
fellow eye served as a control. The "6h" group wore the lens for 6 h; the "24h"
group wore the lens for 24 h; each group provided separate retina and RPE
tissues. Group "24hC" wore the lens for 24 h and provided combined retina + RPE
tissue. Quantitative PCR was used to measure the relative differences (treated
eye vs. control eye) in mRNA levels for 66 candidate genes. In the retina after 6
h, mRNA levels for seven genes were significantly regulated: EGR1 and FOS (early
intermediate genes) were down-regulated in the treated eyes. Genes with secreted
protein products, BMP2 and CTGF, were down-regulated, whilst FGF10, IL18, and SST
were up-regulated. After 24 h the pattern changed; only one of the seven genes
still showed differential expression; BMP2 was still down-regulated. Two new
genes with secreted protein products, IGF2 and VIP, were up-regulated. In the
RPE, consistent with its role in receiving, processing, and transmitting GO
signaling, differential expression was found for genes whose protein products are
at the cell surface, intracellular, in the nucleus, and are secreted. After 6 h,
mRNA levels for 17 genes were down-regulated in the treated eyes, whilst four
genes (GJA1, IGF2R, LRP2, and IL18) were up-regulated. After 24 h the pattern was
similar; mRNA levels for 14 of the same genes were still down-regulated; only
LRP2 remained up-regulated. mRNA levels for six genes no longer showed
differential expression, whilst nine genes, not differentially expressed at 6 h,
now showed differential expression. In the combined retina + RPE after 24 h, mRNA
levels for only seven genes were differentially regulated despite the
differential expression of many genes in the RPE. Four genes showed the same
expression in combined tissue as in retina alone, including up-regulation of VIP
despite significant VIP down-regulation in RPE. Thus, hyperopia-induced GO
signaling, as measured by differential gene expression, differs in the retina and
the RPE. Retinal gene expression changed between 6 h and 24 h of treatment,
suggesting evolution of the retinal response. Gene expression in the RPE was
similar at both time points, suggesting sustained signaling. The combined retina
+ RPE does not accurately represent gene expression in either retina or,
especially, RPE. When gene expression signatures were compared with those in
choroid and sclera, GO signaling, as encoded by differential gene expression,
differs in each compartment of the direct emmetropization signaling cascade.
PMID- 29329976
TI - Therapeutic potential of spinal GLP-1 receptor signaling.
AB - GLP-1 signaling pathway has been well studied for its role in regulating glucose
homeostasis, as well as its beneficial effects in energy and nutrient metabolism.
A number of drugs based on GLP-1 have been used to treat type 2 diabetes
mellitus. GLP-1R is expressed in multiple organs and numerous experimental
studies have demonstrated that GLP-1 signaling pathway exhibits pro-survival
functions in various disorders. In the central nervous system, stimulation of GLP
1R produces neuroprotective effects in specific neurodegenerative disorders, such
as Alzheimer's disease and Parkinson's disease. The preproglucagon neurons
located in the brainstem can also produce GLP-1. GLP-1 analogs have a long-acting
effect and are able to pass the blood-brain barrier, which probably extends the
therapeutic efficacy of GLP-1R activation. Neurodegenerative or traumatic
conditions can damage the spinal cord and result in motor and sensory
dysfunction. Evidence supports that GLP-1R activation in the spinal cord
possesses beneficial effects and significant therapeutic potential. Herein, we
review studies that have focused on GLP-1 and the spinal cord, and summarize the
expression of GLP-1R and the innervation of PPG neurons in the spinal cord, as
well as the potential therapeutic benefits of GLP-1R activation.
PMID- 29329977
TI - Recent insights in the use of nanocarriers for the oral delivery of bioactive
proteins and peptides.
AB - Bioactive proteins and peptides have been used with either prophylactic or
therapeutic purposes, presenting inherent advantages as high specificity and
biocompatibility. Nanocarriers play an important role in the stabilization of
proteins and peptides, offering enhanced buccal permeation and protection while
crossing the gastrointestinal tract. Moreover, preparation of nanoparticles as
oral delivery systems for proteins/peptides may include tailored formulation
along with functionalization aiming bioavailability enhancement of carried
proteins or peptides. Oral delivery systems, namely buccal delivery systems,
represent an interesting alternative route to parenteric delivery systems to
carry proteins and peptides, resulting in higher comfort of administration and,
therefore, compliance to treatment. This paper outlines an extensive overview of
the existing publications on proteins/peptides oral nanocarriers delivery
systems, with special focus on buccal route. Manufacturing aspects of most
commonly used nanoparticles for oral delivery (e.g. polymeric nanoparticles using
synthetic or natural polymers and lipid nanoparticles) advantages and limitations
and potential applications of nanoparticles as proteins/peptides delivery systems
will also be thoroughly addressed.
PMID- 29329975
TI - Risk of suicide and non-fatal self-harm after bariatric surgery: results from two
matched cohort studies.
AB - BACKGROUND: Bariatric surgery reduces mortality, but might have adverse effects
on mental health. We assessed the risk of suicide and self-harm after bariatric
surgery compared with non-surgical obesity treatment. METHODS: Suicide and non
fatal self-harm events retrieved from nationwide Swedish registers were examined
in two cohorts. The non-randomised, prospective Swedish Obese Subjects (SOS)
study compared bariatric surgery (n=2010; 1369 vertical-banded gastroplasty, 376
gastric banding, and 265 gastric bypass) with usual care (n=2037; recruitment
1987-2001). The second cohort consisted of individuals from the Scandinavian
Obesity Surgery Registry (SOReg; n=20 256 patients who had gastric bypass)
matched to individuals treated with intensive lifestyle modification (n=16 162;
intervention 2006-13) on baseline BMI, age, sex, education level, diabetes,
cardiovascular disease, history of self-harm, substance misuse, antidepressant
use, anxiolytics use, and psychiatric health-care contacts. FINDINGS: During 68
528 person-years (median 18; IQR 14-21) in the SOS study, suicides or non-fatal
self-harm events were higher in the surgery group (n=87) than in the control
group (n=49; adjusted hazard ratio [aHR] 1.78, 95% CI 1.23-2.57; p=0.0021); of
these events, nine and three were suicides, respectively (3.06, 0.79-11.88;
p=0.11). In analyses by primary procedure type, increased risk of suicide or non
fatal self-harm was identified for gastric bypass (3.48, 1.65-7.31; p=0.0010),
gastric banding (2.43, 1.23-4.82; p=0.011), and vertical-banded gastroplasty
(2.25, 1.37-3.71; p=0.0015) compared with controls. Out of nine deaths by suicide
in the SOS surgery group, five occurred after gastric bypass (two primary and
three converted procedures). During 149 582 person-years (median 3.9; IQR 2.8
5.2), more suicides or non-fatal self-harm events were reported in the SOReg
gastric bypass group (n=341) than in the intensive lifestyle group (n=84; aHR
3.16, 2.46-4.06; p<0.0001); of these events, 33 and five were suicides,
respectively (5.17, 1.86-14.37; p=0.0017). In SOS, substance misuse during follow
up was recorded in 48% (39/81) of patients treated with surgery and 28% (13/47)
of controls with non-fatal self-harm events (p=0.023). Correspondingly, substance
misuse during follow-up was recorded in 51% (162/316) of participants in the
SOReg gastric bypass group and 29% (23/80) of participants in the intensive
lifestyle group with non-fatal self-harm events (p=0.0003). The risk of suicide
and self-harm was not associated with poor weight loss outcome. INTERPRETATION:
Bariatric surgery was associated with suicide and non-fatal self-harm. However,
the absolute risks were low and do not justify a general discouragement of
bariatric surgery. The findings indicate a need for thorough preoperative
psychiatric history assessment along with provision of information about
increased risk of self-harm following surgery. Moreover, the findings call for
postoperative surveillance with particular attention to mental health. FUNDING:
US National Institutes of Health and Swedish Research Council.
PMID- 29329978
TI - Data quality over data quantity in computational cognitive neuroscience.
AB - We analyzed factors that may hamper the advancement of computational cognitive
neuroscience (CCN). These factors include a particular statistical mindset, which
paves the way for the dominance of statistical power theory and a preoccupation
with statistical replicability in the behavioral and neural sciences. Exclusive
statistical concerns about sampling error occur at the cost of an inadequate
representation of the problem of measurement error. We contrasted the
manipulation of data quantity (sampling error, by varying the number of subjects)
against the manipulation of data quality (measurement error, by varying the
number of data per subject) in a simulated Bayesian model identifiability study.
The results were clear-cut in showing that - across all levels of signal-to-noise
ratios - varying the number of subjects was completely inconsequential, whereas
the number of data per subject exerted massive effects on model identifiability.
These results emphasize data quality over data quantity, and they call for the
integration of statistics and measurement theory.
PMID- 29329979
TI - How acute stress may enhance subsequent memory for threat stimuli outside the
focus of attention: DLPFC-amygdala decoupling.
AB - Stress-related disorders, e.g., anxiety and depression, are characterized by
decreased top-down control for distracting information, as well as a memory bias
for threatening information. However, it is unclear how acute stress biases
mnemonic encoding and leads to prioritized storage of threat-related information
even if outside the focus of attention. In the current study, healthy adults (N =
53, all male) were randomly assigned to stress induction using the socially
evaluated cold-pressor test (SECPT) or a control condition. Participants
performed a task in which they were required to identify a target letter within a
string of letters that were either identical to the target and thereby
facilitating detection (low distractor load) or mixed with other letters to
complicate the search (high load). Either a fearful or neutral face was presented
on the background, outside the focus of attention. Twenty-four hours later,
participants were asked to perform a surprise recognition memory test for those
background faces. Stress induction resulted in increased cortisol and negative
subjective mood ratings. Stress did not affect visual search performance,
however, participants in the stress group showed stronger memory compared to the
control group for fearful faces in the low attentional load condition.
Critically, the stress induced memory bias was accompanied by decoupling between
amygdala and DLFPC during encoding, which may represent a mechanism for decreased
ability to filter task-irrelevant threatening background information. The current
study provides a potential neural account for how stress can produce a negative
memory bias for threatening information even if presented outside the focus of
attention. Despite of an adaptive advantage for survival, such tendencies may
ultimately also lead to generalized fear, a possibility requiring additional
investigation.
PMID- 29329980
TI - A mass spectrometry imaging approach for investigating how drug-drug interactions
influence drug blood-brain barrier permeability.
AB - There is a high need to develop quantitative imaging methods capable of providing
detailed brain localization information of several molecular species
simultaneously. In addition, extensive information on the effect of the blood
brain barrier on the penetration, distribution and efficacy of neuroactive
compounds is required. Thus, we have developed a mass spectrometry imaging method
to visualize and quantify the brain distribution of drugs with varying blood
brain barrier permeability. With this approach, we were able to determine blood
brain barrier transport of different drugs and define the drug distribution in
very small brain structures (e.g., choroid plexus) due to the high spatial
resolution provided. Simultaneously, we investigated the effect of drug-drug
interactions by inhibiting the membrane transporter multidrug resistance 1
protein. We propose that the described approach can serve as a valuable
analytical tool during the development of neuroactive drugs, as it can provide
physiologically relevant information often neglected by traditional imaging
technologies.
PMID- 29329981
TI - Molecular cloning and characterization of leucine aminopeptidase gene from Taenia
pisiformis.
AB - Leucine aminopeptidase (LAP, EC: 3.4.11.1) is an important metalloexopeptidase
that catalyze the hydrolysis of amino-terminal leucine residues from polypeptides
and proteins. In this study, a full length of cDNA encoding leucine
aminopeptidase of Taenia pisiformis (TpLAP) was cloned by rapid amplification of
cDNA-ends using the polymerase chain reaction (RACE-PCR) method. The full-length
cDNA of the TpLAP gene is 1823 bp and contains a 1569 bp ORF encoding 533 amino
acids with a putative mass of 56.4 kDa. TpLAP contains two characteristic motifs
of the M17LAP family in the C-terminal sequence: the metal binding site 265
[VGKG]-271 and the catalytic domain motif 351-[NTDAEGRL]-357. The soluble GST
TpLAP protein was expressed in Escherichia coli Transetta (DE3) and four specific
anti-TpLAP monoclonal antibodies (mAbs) were prepared. In enzymatic assays, the
optimal activity was observed at pH 9.5 at 45 degrees C. GST-TpLAP displayed a
hydrolyzing activity for the Leu-pNA substrate with a maximum activity of 46
U/ml. The enzymatic activity was significantly enhanced by Mn2+ and completely
inhibited by 20 nM bestatin and 0.15 mM EDTA. The native TpLAP was detected
specifically in ES components of adult T. pisiformis by western blotting using
anti-TpLAP mAb as a probe. Quantitative real-time PCR revealed that the TpLAP
gene was expressed at a high level in adult worm tissues, especially in the
gravid proglottids (50.71-fold). Immunolocalization analysis showed that TpLAP
was located primarily in the subtegumental parenchyma zone and the uterine wall
of adult worms. Our results indicate that TpLAP is a new member of the M17LAP
family and can be considered as a stage-differentially expressed protein. These
findings might provide new insights into the study of the mechanisms of growth,
development and survival of T. pisiformis in the final host and have potential
value as an attractive target for drug therapy or vaccine intervention.
PMID- 29329982
TI - Gongylonema pulchrum infection in the human oral cavity: A case report and
literature review.
AB - Gongylonema infection is a zoonotic disease occurring throughout the world and is
mainly caused by consumption of contaminated water and raw food. Adult
Gongylonema worms can exist as parasites in the human body for up to 10 years and
cause symptoms of local irritation in the oral cavity, esophagus, and pharynx.
Herein, we report a rare case in which live Gongylonema pulchrum was detected and
extracted from the oral cavity of a woman. The pathogen was confirmed as G.
pulchrum on the basis of microscopic examination and morphologic analysis. The
patient's symptoms resolved immediately after surgical removal of the parasite,
and the patient has been advised not to drink water that has not been boiled and
to avoid consuming unwashed raw vegetables.
PMID- 29329984
TI - Infralimbic dopamine D2 receptors mediate glucocorticoid-induced facilitation of
auditory fear memory extinction in rats.
AB - The infralimbic (IL) cortex of the medial prefrontal cortex plays an important
role in the extinction of fear memory. Also, it has been showed that both brain
glucocorticoid and dopamine receptors are involved in many processes such as fear
extinction that drive learning and memory; however, the interaction of these
receptors in the IL cortex remains unclear. We examined a putative interaction
between the effects of glucocorticoid and dopamine receptors stimulation in the
IL cortex on fear memory extinction in an auditory fear conditioning paradigm in
male rats. Corticosterone (the endogenous glucocorticoid receptor ligand), or
RU38486 (the synthetic glucocorticoid receptor antagonist) microinfusion into the
IL cortex 10 min before test 1 attenuated auditory fear expression at tests 1-3,
suggesting as an enhancement of fear extinction. The effect of corticosterone,
but not RU38486 was counteracted by the dopamine D2 receptor antagonist sulpiride
pre-treatment administered into the IL (at a dose that failed to alter freezing
behavior on its own). In contrast, intra-IL infusion of the dopamine D1 receptor
antagonist SCH23390 pre-treatment failed to alter freezing behavior. These
findings provide evidence for the involvement of the IL cortex D2 receptors in
CORT-induced facilitation of fear memory extinction.
PMID- 29329983
TI - Attenuation of noise-induced hyperactivity in the dorsal cochlear nucleus by pre
treatment with MK-801.
AB - It has previously been hypothesized that hyperactivity of central auditory
neurons following exposure to intense noise is a consequence of synaptic
alterations. Recent studies suggest the involvement of NMDA receptors in the
induction of this hyperactive state. NMDA receptors can mediate long term changes
in the excitability of neurons through their involvement in excitotoxic injury
and long term potentiation and depression. In this study, we examined the effect
of administering an NMDA receptor blocker on the induction of hyperactivity in
the dorsal cochlear nucleus (DCN) following intense sound exposure. Our
prediction was that if hyperactivity induced by intense sound exposure is
dependent on NMDA receptors, then blocking these receptors by administering an
NMDA receptor antagonist just before animals are exposed to intense sound should
reduce the degree of hyperactivity that subsequently emerges. We compared the
levels of hyperactivity that develop in the DCN after intense sound exposure to
activity recorded in control animals that were not sound exposed. One group of
animals to be sound exposed received intraperitoneal injection of MK-801 twenty
minutes preceding the sound exposure, while the other group received injection of
saline. Recordings performed in the DCN 26-28 days post-exposure revealed
increased response thresholds and widespread increases in spontaneous activity in
the saline-treated animals that had been sound exposed, consistent with earlier
studies. The animals treated with MK-801 preceding sound exposure showed
similarly elevated thresholds but an attenuation of hyperactivity in the DCN; the
attenuation was most robust in the high frequency half of the DCN, but lower
levels of hyperactivity were also found in the low frequency half. These findings
suggest that NMDA receptors are an important component of the hyperactivity
inducing mechanism following intense sound exposure. They further suggest that
blockade of NMDA receptors may offer a useful therapeutic approach to preventing
induction of noise-induced hyperactivity-related hearing disorders, such as
tinnitus and hyperacusis.
PMID- 29329985
TI - The scavenger activity of the human P2X7 receptor differs from P2X7 pore function
by insensitivity to antagonists, genetic variation and sodium concentration:
Relevance to inflammatory brain diseases.
AB - Activation of P2X7 receptors is widely recognised to initiate proinflammatory
responses. However P2X7 also has a dual function as a scavenger receptor which is
active in the absence of ATP and plasma proteins and may be important in central
nervous system (CNS) diseases. Here, we investigated both P2X7 pore formation and
its phagocytic function in fresh human monocytes (as a model of microglia) by
measuring ATP-induced ethidium dye uptake and fluorescent bead uptake
respectively. This was studied in monocytes expressing various polymorphic
variants as well as in the presence of different P2X7 antagonists and ionic
media. P2X7-mediated phagocytosis was found to account for about half of
Latrunculin (or Cytochalasin D)-sensitive bead engulfment by fresh human
monocytes. Monocytes harbouring P2X7 Ala348Thr or Glu496Ala polymorphic variants
showed increase or loss of ethidium uptake respectively, but these changes in
pore formation did not always correspond to the changes in phagocytosis of YG
beads. Unlike pore function, P2X7-mediated phagocytosis was not affected by three
potent selective P2X7 antagonists and remained identical in Na+ and K+ media.
Taken together, our results show that P2X7 is a scavenger receptor with important
function in the CNS but its phagocytic function has features distinct from its
pore function. Both P2X7 pore formation and P2X7-mediated phagocytosis should be
considered in the design of new P2X7 antagonists for the treatment of CNS
diseases.
PMID- 29329986
TI - Prospects in non-invasive assessment of liver fibrosis: Liquid biopsy as the
future gold standard?
AB - Liver fibrosis is the result of persistent liver injury, and is characterized by
sustained scar formation and disruption of the normal liver architecture. The
extent of fibrosis is considered as an important prognostic factor for the
patient outcome, as an absence of (early) treatment can lead to the development
of liver cirrhosis and hepatocellular carcinoma. Till date, the most sensitive
and specific way for the diagnosis and staging of liver fibrosis remains liver
biopsy, an invasive diagnostic tool, which is associated with high costs and
discomfort for the patient. Over time, non-invasive scoring systems have been
developed, of which the measurements of serum markers and liver stiffness are
validated for use in the clinic. These tools lack however the sensitivity and
specificity to detect small changes in the progression or regression of both
early and late stages of fibrosis. Novel non-invasive diagnostic markers with the
potential to overcome these limitations have been developed, but often lack
validation in large patient cohorts. In this review, we will summarize novel
trends in non-invasive markers of liver fibrosis development and will discuss
their (dis-)advantages for use in the clinic.
PMID- 29329987
TI - Quantitative proteomics in Friedreich's ataxia B-lymphocytes: A valuable approach
to decipher the biochemical events responsible for pathogenesis.
AB - Friedreich's ataxia (FRDA) represents the most frequent type of autosomal
recessively inherited ataxia and is caused by the deficiency of frataxin, a
mitochondrial protein. It is known that frataxin-deficiency leads to alterations
in cellular and mitochondrial iron metabolism and impacts in the cell physiology
at several levels. Frataxin is thought to play a role in iron-sulfur cluster
biogenesis and heme synthesis. Currently, cellular antioxidant defense is
dysregulated when frataxin is deficient, which exacerbates oxidative damage in
FRDA. Moreover, alterations in lipid metabolism have been observed in several
models of the disease. To better understand the biochemical sequelae of frataxin
reduction, global protein expression analysis was performed using quantitative
proteomic experiments in Friedreich's ataxia patient-derived B-lymphocytes as
compared to controls. We were able to confirm a subset of changes in these cells
and importantly, we observed previously unreported signatures of protein
expression. Among the novel protein signatures that we have identified, the
decrease in CHCHD4 might partly explain some aspects of the molecular
pathogenesis of FRDA. The identification of a core set of proteins changing in
the FRDA pathogenesis is a useful tool in trying to decipher the function(s) of
frataxin in order to clarify the mitochondrial metabolic disease process.
PMID- 29329989
TI - Reassessment of Right Middle Lobe Lung Cancer: Comparison of Segments 4 and 5
Tumors.
AB - BACKGROUND: The purpose of this study was to elucidate the clinical behavior of
right middle lobe lung cancer, with focus on the tumor location. METHODS: We
reviewed retrospectively 711 patients who underwent lobectomy or bilobectomy for
clinical stage I non-small cell lung cancer (upper lobe, 346; middle lobe, 82;
lower lobe, 283). Factors affecting survival were assessed by log rank tests and
Cox regression analyses. RESULTS: The prognosis of patients with segment 5 tumors
(n = 39) was significantly worse than that of patients with segment 4 tumors (n =
43; 5-year overall survival rates, 69.8% versus 87.6%, p = 0.040; and 5-year
recurrence-free survival rates, 58.4% versus 73.0%, p = 0.029). Segment 5 tumors
were an independent factor for poor prognosis in multivariable Cox regression
analysis, and tended to cause more pathologic mediastinal lymph node metastases
than segment 4 tumors (12.8% versus 2.3%, p = 0.097). Compared with tumors in the
other lobes, patients with segment 4 tumors demonstrated no significant
difference in prognosis; however, patients with segment 5 tumors demonstrated a
significantly and outstandingly worse prognosis than patients with other lobe
tumors (5-year overall survival rates, 69.8% versus 82.2%, p = 0.020; and 5-year
recurrence-free survival rates, 58.4% versus 71.4%, p = 0.0071). CONCLUSIONS:
Patients with segment 5 tumors had a worse prognosis than patients with segment 4
and other lobe tumors. We speculate that is because segment 5 tumors cause more
metastases to the mediastinal lymph nodes. Tumor location was an important
prognostic factor for patients with right middle lobe lung cancer.
PMID- 29329988
TI - Rethinking Medicaid Coverage and Payment Policy to Promote High Value Care: The
Case of Long-Acting Reversible Contraception.
AB - CONTEXT: Long-acting reversible contraception (LARC) is the most effective
reversible method to prevent unplanned pregnancies. Variability in state-level
policies and the high cost of LARC could create substantial inconsistencies in
Medicaid coverage, despite federal guidance aimed at enhancing broad access. This
study surveyed state Medicaid payment policies and outreach activities related to
LARC to explore the scope of services covered. METHODS: Using publicly available
information, we performed a content analysis of state Medicaid family planning
and LARC payment policies. Purposeful sampling led to a selection of nine states
with diverse geographic locations, political climates, Medicaid expansion status,
and the number of women covered by Medicaid. RESULTS: All nine states' Medicaid
programs covered some aspects of LARC. However, only a single state's payment
structure incorporated all core aspects of high-quality LARC service delivery,
including counseling, device, insertion, removal, and follow-up care. Most states
did not explicitly address counseling, device removal, or follow-up care. Some
states had strategies to enhance access, including policies to increase device
reimbursement, stocking and delivery programs to remove cost barriers, and
covering devices and insertion after an abortion. CONCLUSIONS: Although Medicaid
policy encourages LARC methods, state payment policies frequently fail to address
key aspects of care, including counseling, follow-up care, and removal, resulting
in highly variable state-level practices. Although some states include payment
policy innovations to support LARC access, significant opportunities remain.
PMID- 29329990
TI - Transcatheter Aortic Valve Implantation in Morphologically Complex Root
Aneurysms.
AB - Performing transcatheter aortic valve implantation in the presence of
aneurysmatic aortopathy is widely contraindicated but needs to be taken into
account as a bailout strategy in selected patients. Deliberate preoperative
assessment of measurements becomes the crucial key element in this context. After
meticulous valve selection, retrograde access is obtained through the right
subclavian artery additionally serving as a backup arterial cannulation site in
case of conversion. Transcatheter aortic valve implantation is then performed
through the transapical route. Transcatheter aortic valve implantation in complex
aneurysmatic aortic morphology is feasible in highly selected patients after
comprehensive preoperative evaluation. The present article describes our initial
experience, safeguards, and technical details.
PMID- 29329991
TI - Dynamic contrast-enhanced EUS for quantification of tumor perfusion in colonic
cancer: a prospective cohort study.
AB - BACKGROUND AND AIMS: Dynamic contrast-enhanced EUS (CE-EUS) for quantification of
perfusion in colonic tumors has not previously been reported in the literature.
The aim of this study was to investigate correlations between perfusion
parameters and vessel density assessed by immunohistochemical staining with
antibodies toward CD31 and CD105. METHODS: We conducted a prospective clinical
study of 28 patients with left-sided colonic adenocarcinoma who underwent CE-EUS
and left-sided hemicolectomy within 2 weeks. CE-EUS recordings were analyzed in 2
regions of interest: the entire tumor and the most enhanced area.
Immunohistochemical staining with CD31 and CD105 was performed on tumor tissue
sections. The slides were manually scanned for highly vascularized areas, and
counting of vessels was performed in hotspots within the tumor and invasive
front. New vasculature was assessed by CD105. Associations between CE-EUS and
CD31 and CD105 were investigated using Spearman correlation. RESULTS: We found
significant P values for the correlation between CD31 and rise time (rho = .603
[95% confidence interval (95% CI), .238-.816]; P = .001) in tumor tissue and for
the correlation between CD31 and rise time (rho = .50 [95% CI, .201-.695]; P =
.008) and fall time (rho = .52 [95% CI, .204-.723]; P = .006) corresponding to
the invasive front. We found no correlations between perfusion values evaluated
by CE-EUS and CD105. CONCLUSIONS: Our results show a significant correlation for
vessel density evaluated by CD31 and perfusion parameters evaluated by CE-EUS.
This may be the first step toward using real-time CE-EUS for monitoring
antiangiogenic therapies in colonic cancer. (Clinical trial registration number:
NCT02324023.).
PMID- 29329993
TI - Pulmonary arterial hypertension in four patients treated by leflunomide.
AB - Pulmonary arterial hypertension (PAH) is a rare disorder that can be drug
induced, mostly following treatment by appetite-suppressant drugs. We report four
cases of patients who developed PAH following a treatment by leflunomide for
rheumatoid arthritis, psoriatic arthritis or undetermined connective tissue
disease. All patients described a progressive dyspnea from grade II to IV of NYHA
classification; clinical examination found signs of heart failure. PAH was
finally diagnosed and confirmed by right heart catheterisation. Haemodynamic
explorations found pre-capillary pulmonary hypertension with mean pulmonary
arterial pressure above 25mmHg, and pulmonary capillary wedge pressure under
15mmHg. Explorations of this pre-capillary pulmonary hypertension were conducted
according to international guidelines: pulmonary or chronic thromboembolic
aetiologies were excluded after ventilation/perfusion lung scan and high
resolution computed tomography. All other etiologic explorations were negative.
Imputability of leflunomide was finally retained. Leflunomide was stopped for all
patients; three of them received specific PAH treatments. A favourable clinical
and/or haemodynamic evolution was observed for all patients. The conclusions of
the investigations conducted by our pharmacovigilance centre were communicated to
the European Medicines Agency, leading to the addition of "pulmonary
hypertension" in the paragraph "special warning and precautions of use" of the
package leaflet of leflunomide.
PMID- 29329992
TI - EUS elastography (strain ratio) and fractal-based quantitative analysis for the
diagnosis of solid pancreatic lesions.
AB - BACKGROUND AND AIMS: EUS elastography is useful in characterizing solid
pancreatic lesions (SPLs), and fractal analysis-based technology has been used to
evaluate geometric complexity in oncology. The aim of this study was to evaluate
EUS elastography (strain ratio) and fractal analysis for the characterization of
SPLs. METHODS: Consecutive patients with SPLs were prospectively enrolled between
December 2015 and February 2017. Elastographic evaluation included parenchymal
strain ratio (pSR) and wall strain ratio (wSR) and was performed with a new
compact US processor. Elastographic images were analyzed using a computer program
to determine the 3-dimensional histogram fractal dimension. A composite
cytology/histology/clinical reference standard was used to assess sensitivity,
specificity, positive predictive value, negative predictive value, and area under
the receiver operating curve. RESULTS: Overall, 102 SPLs from 100 patients were
studied. At final diagnosis, 69 (68%) were malignant and 33 benign. At
elastography, both pSR and wSR appeared to be significantly higher in malignant
as compared with benign SPLs (pSR, 24.5 vs 6.4 [P < .001]; wSR, 56.6 vs 15.3 [P <
.001]). When the best cut-off levels of pSR and wSR at 9.10 and 16.2,
respectively, were used, sensitivity, specificity, positive predictive value,
negative predictive value, and area under the receiver operating curve were
88.4%, 78.8%, 89.7%, 76.9%, and 86.7% and 91.3%, 69.7%, 86.5%, 80%, and 85.7%,
respectively. Fractal analysis showed a significant statistical difference (P =
.0087) between the mean surface fractal dimension of malignant lesions (D = 2.66
+/- .01) versus neuroendocrine tumor (D = 2.73 +/- .03) and a statistical
difference for all 3 channels red, green, and blue (P < .0001). CONCLUSIONS: EUS
elastography with pSR and fractal-based analysis are useful in characterizing
SPLs. (Clinical trial registration number: NCT02855151.).
PMID- 29329994
TI - Authors' response to the comments to "Structured pharmacist-led intervention
programme to improve medication adherence in COPD patients: A randomized
controlled study".
PMID- 29329995
TI - Multifunctional hybrid graphene oxide for circulating tumor cell isolation and
analysis.
AB - Even in 21st century, >90% cancer-associated deaths are caused by metastatic
disease. Circulating tumor cells (CTCs), which circulate in the blood stream
after release from primary tumors, extravasate and form fatal metastases in
different organs. Several clinical trials indicate that CTCs can be used as a
liquid biopsy of tumors for early diagnosis of cancers. Since CTCs are extremely
rare and exhibit heterogeneous biology due to epithelial-mesenchymal transition
(EMT), oncologists continue to face enormous challenges in using CTCs as a true
"liquid biopsy" for cancer patients. Recent advancements in nanoscience allow us
to design nano-architectures with the capability of targeted CTCs isolation and
identification. In the current review, we discuss contribution from different
groups on the development of graphene oxide based nanoarchitecture for effective
isolation and accurate identification of CTCs from whole blood. In the last few
years, using zero-dimensional (0D), two dimensional (2D) and three dimensional
(3D) multifunctional hybrid graphene oxide (GO), different types of
nanoarchitectures have been designed. These nanoarchitectures represent a highly
powerful platform for CTC diagnosis. We discuss the major design criteria that
have been used to develop hybrid GO nanoarchitectures for selective capture and
accurate identification of heterogeneous CTCs from whole blood. At the end, we
conclude with the promises, major challenges, and prospect to clinically
translate the identification of CTCs using GO based nanotechnology.
PMID- 29329996
TI - To prep or not to prep - that is the question: A randomized trial on the use of
antiflatulent medication as part of bowel preparation for patients having image
guided external beam radiation therapy to the prostate.
AB - INTRODUCTION: Radiation therapy is a standard treatment option for prostate
cancer. With growing use of escalated doses and tighter margins, procedures to
limit rectal size variation are needed to reduce prostate motion, increase
treatment accuracy, and minimize rectal toxicity. This prospective study was done
to determine whether the introduction of an antiflatulent medication would
decrease rectal distention at computed tomography (CT) simulation and throughout
a course of radiation therapy. METHODS AND MATERIALS: Patients undergoing a
radical course of radiation therapy to the prostate/prostate bed were eligible to
participate. Participants were randomly assigned to the intervention arm
(antiflatulent medication) or the control arm (no medication). For each
participant, the number of CT simulation rescans was recorded. Rectal diameters
were measured on CT simulation and treatment cone beam CT scans. Acute rectal
toxicities were assessed at baseline and weekly using National Cancer Institute
Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0. A chi2
analysis was used to compare the number of participants requiring a rescan in
each study arm. Change in rectal diameter over time was assessed using repeated
measures analysis of variance. RESULTS: A total of 78 patients participated, with
equal numbers assigned to each study arm. There was no significant difference
between arms in the number of participants requiring a CT simulation rescan (P =
.5551). There was no significant variation in rectal diameter between arms (P =
.8999); however, there was a significant effect of time (P = .0017) and a
significant interaction effect between study arm and time on rectal diameter (P =
.0141). No acute rectal toxicities above grade 2 were reported. CONCLUSIONS: The
addition of antiflatulent medication did not affect the frequency of CT
simulation rescans. Both time and the interaction between study arm and time had
a statistically significant effect on rectal diameter, although neither finding
was clinically significant. Instead, standardized bowel preparation education
developed for this study may have been sufficient to limit rectal size variation.
PMID- 29329997
TI - Clinical log data analysis for assessing the accuracy of the CyberKnife fiducial
free lung tumor tracking system.
AB - PURPOSE: The CyberKnife Xsight Lung Tracking (XLT) and 1-View tracking systems
can synchronize beam targeting to a visible lung tumor with respiratory motion
during irradiation without requiring internal fiducial markers. The systems use a
correlation model that relates external marker positions to tumor positions as
well as a prediction model that predicts the target's future position. In this
study, the correlation and prediction model uncertainties related to the
CyberKnife fiducial-free tumor tracking system were evaluated using clinical log
data. METHODS AND MATERIALS: Data from 211 fractions in 42 patients with lung
tumors were analyzed. Log files produced by the CyberKnife Synchrony system were
acquired after each treatment; the mean correlation and prediction errors for
each patient were calculated. Additionally, we examined the tracking tumor
related parameters and analyzed the relationships between the model errors and
tracking tumor-related parameters. RESULTS: The overall means +/- standard
deviations (SDs) of the correlation errors were 0.70 +/- 0.43 mm, 0.36 +/- 0.16
mm, 0.44 +/- 0.22 mm, and 0.95 +/- 0.43 mm for the superoinferior (SI), left
right (LR), anteroposterior (AP), and radial directions, respectively. The
overall means +/- SDs of the prediction errors were 0.13 +/- 0.11 mm, 0.03 +/-
0.02 mm, 0.03 +/- 0.02 mm, and 0.14 +/- 0.11 mm for the SI, LR, AP, and radial
directions, respectively. There were no significant differences in these errors
between the XLT and 1-View tracking methods. The tumor motion amplitude was
moderately associated with the correlation error and strongly related to the
prediction error in the SI and radial directions. CONCLUSIONS: Clinical log data
analysis can be used to determine the necessary margin sizes in treatment plans
to compensate for correlation and prediction errors in the CyberKnife fiducial
free lung tumor tracking system. The tumor motion amplitude may facilitate margin
determination.
PMID- 29329998
TI - Common error pathways seen in the RO-ILS data that demonstrate opportunities for
improving treatment safety.
AB - PURPOSE: The Radiation Oncology Incident Learning System (RO-ILS) receives event
reports from facilities across the country. This effort extracted common error
pathways seen in the data. These pathways, expressed as fault trees, demonstrate
the need for, and opportunities for, preventing these errors and/or limiting
their propagation to treatment. METHODS AND MATERIALS: As of the third quarter of
2016, 2344 event reports had been submitted to RO-ILS and reviewed. A total of
396 of the reports judged highest priority were rereviewed and assigned up to 3
keywords to classify events. Based on patterns among the keyword assignments, the
data were further aggregated into pathways leading to 3 general error types:
"problematic plan approved for treatment," "wrong shift instructions given to
therapists," and "wrong shift performed at treatment." Fault trees were created
showing how different errors at different stages in the treatment process combine
to flow into these general error types. RESULTS: A total of 173 of the 396 (44%)
events were characterized as belonging to 1 of these 3 general error types.
Ninety-nine events were defined as "problematic plan approved for treatment," 40
as "wrong shift instructions given to therapists," and 34 as "wrong shift
performed at treatment." Seventy-six of these events (44%) resulted in
incorrectly delivered treatment. Event discovery was by therapists (n = 76),
physicists (n = 45), physicians (n = 23), dosimetrists (n = 15), or not
identified (n = 9); 5 events were found as a result of the patient questioning
the staff. For the event type "problematic plan approved for treatment," 64 of
the 99 (65%) events were attributable to physician error: incorrect target or
dosing pattern prescribed. CONCLUSIONS: Data extracted from RO-ILS event reports
demonstrate common error pathways in radiation oncology that propagate all the
way to treatment. Additional study and coordination of efforts is needed to
develop and share best practices to address the sources of these errors and
curtail their propagation.
PMID- 29329999
TI - Understanding melanocortin-4 receptor control of neuronal circuits: Toward novel
therapeutics for obesity syndrome.
AB - It is well known that melanocortin-4 receptors (MC4Rs) and central melanocortin
pathways regulate food intake, energy expenditure, and glucose homeostasis.
Importantly, MC4R deficiency is the most common monogenic cause of human obesity.
Interestingly, MC4Rs expressed by distinct central nuclei are responsible for the
different physiological function of MC4R stimulation. In addition, MC4Rs activate
multiple intracellular and/or synaptic signaling molecules for the regulation of
neuronal circuits. Therefore, MC4Rs and the downstream signal molecules are
plausible targets for development of novel therapeutics against obesity and
obesity-related metabolic disorders. In this review, we discuss recent findings
on the neuronal circuits and signaling molecules that are responsible for MC4R
control energy balance and autonomic function. Further, we review status of MC4R
agonists as novel therapeutics for obesity syndrome. We believe that
comprehensive understanding of signaling molecules involved in MC4R control of
neuronal circuits will help to design MC4R agonists as safe and effective anti
obesity drugs.
PMID- 29330000
TI - Histotripsy Treatment of Benign Prostatic Enlargement Using the Vortx Rx System:
Initial Human Safety and Efficacy Outcomes.
AB - OBJECTIVE: To assess clinical safety (primary) and efficacy (secondary) of
histotripsy for treatment of symptomatic benign prostatic enlargement in a first
in human study. METHODS: Twenty-five male subjects with moderate to severe lower
urinary tract symptoms, prostate size between 30 and 80 g, and no evidence of
prostate cancer were enrolled at 2 sites in a prospective, single-arm study.
Treatment consisted of acoustic energy delivery through the perineum with
integrated real-time transrectal ultrasound monitoring using the Vortx Rx system.
Follow-up evaluations were performed on postoperative day 1 and 1, 3, and 6
months. RESULTS: Twenty-five men underwent histotripsy treatment with no serious
intraoperative adverse events. Postoperatively, 3 cases of transient urinary
retention (<3 days), 1 case of urinary retention (8 days in duration, defined as
serious), a minor anal abrasion, and microscopic hematuria were considered device
related adverse events. Debulking of targeted prostate tissue was not observed
with transrectal ultrasound imaging or with endoscopic visualization, and
clinically meaningful improvement in uroflow or postvoid residual urine (PVR) did
not occur. However, International Prostate Symptom Score improvement at 1 month
was 12.5 (52.4%) +/- 6.6 points (n = 25), at 3 months was 11.9 (50.8%) +/- 7.6
points (n = 24), and at 6 months was 10.4 (44.0%) +/- 7.6 points (n = 24) (P
<.001). CONCLUSION: Prostate histotripsy was safe and well tolerated in this
pilot human trial with improvement in lower urinary tract symptoms.
PMID- 29330001
TI - In-bore 3.0-T Magnetic Resonance Imaging-guided Transrectal Targeted Prostate
Biopsy in a Repeat Biopsy Population: Diagnostic Performance, Complications, and
Learning Curve.
AB - OBJECTIVE: To evaluate the diagnostic performance and complication rate of the in
bore magnetic resonance imaging-guided transrectal targeted prostate biopsy
(MRGB) in a repeat biopsy population on the basis of a nearly 4-year learning
curve (2014-2017). MATERIALS AND METHODS: A total of 142 consecutive males with
previous biopsies and persistent suspicion of prostate cancer (PCa) due to high
prostate-specific antigen level initially underwent MRGB in the case of prostate
imaging reporting and data system (PI-RADS) 3-5 lesions. Cancer detection rate
(CDR), number and length of cores, biopsy time, operator experience,
complications, and prediction of clinically significant (cs) PCa (Gleason score
>=7) were investigated. RESULTS: PCa was found in 57% of patients. CDR in PI-RADS
3, 4, and 5 lesions were 46%, 52%, and 74%, respectively. csPCa was found in 9%,
25%, and 48% of patients. In univariate analysis the PI-RADS score (P = .0067)
was a significant predictor of csPCa. In the multivariate logistic regression,
age (P = .0007), number of previous biopsies (P = .0236), and prostate-specific
antigen density (P = .0250) were significant predictors of csPCa. Location and
size of the index lesion, number and length of cores obtained, and operator
experience did not affect CDR. Concerning learning curve, biopsy time and number
of cores obtained improved significantly after 10 procedures. Complications
requiring medical intervention were seen in 6% (infections 2%). CONCLUSION: In a
re-biopsy setting the MRGB showed sufficient diagnostic performance in detecting
csPCa in PI-RADS 3-5 lesions, with low complication rate. The skill of performing
biopsy is quickly acquired, and location of index lesion did not have an impact
on CDR.
PMID- 29330002
TI - Choosing a healthy and sustainable diet: A three-level approach for understanding
the drivers of the Italians' dietary regime over time.
AB - Dietary patterns play key roles in health promotion and in preserving the
environment. A growing number of studies show the importance of individual
factors on food consumption choices, such as socio-economic status, lifestyle
variables and contextual and social factors that characterize the geographical
area in which individuals reside. The Mediterranean Diet is a sustainable diet
that respects the environment, thus reducing per capita emissions from food
production in respect to less sustainable diet. The aim of this paper is to
determine the Italians' prevailing food patterns using a composite indicator and
to identify which factors determine a higher adherence to the Mediterranean Diet
in Italy. By using 15 waves of the ISTAT "Aspect of Daily Life" survey, we
constructed an original data set and referred to the multilevel approach which
enabled us to distinguish between temporal and cross-sectional effects thus
providing valuable insights to policy makers and stakeholders in order to promote
the Mediterranean Diet and reap environmental and public health. The results show
that education plays an important role in determining food consumption behavior
while the tendency to practice sports on a regular basis and to have breakfast
and lunch at home positively influence people's adherence to this diet.
PMID- 29330003
TI - Effects of 5-HT5A receptor blockade on amnesia or forgetting.
AB - Previously the effects (0.01-3.0 mg/kg) of post-training SB-699551 (a 5-HT5A
receptor antagonist) were reported in the associative learning task of
autoshaping, showing that SB-699551 (0.1 mg/kg) decreased lever-press conditioned
responses (CR) during short-term (STM; 1.5-h) or (3.0 mg/kg) long-term memory
(LTM; 24-h); relative to the vehicle animals. Moreover, as pro-cognitive efficacy
of SB-699551 was reported in the ketamine-model of schizophrenia. Hence, firstly
aiming improving performance (conditioned response, CR), in this work autoshaping
lever-press vs. nose-poke response was compared; secondly, new set of animals
were randomly assigned to SB-699551 plus forgetting or amnesia protocols. Results
show that the nose-poke operandum reduced inter-individual variance, increased CR
and produced a progressive CR until 48-h. After one week of no training/testing
sessions (i.e., interruption of 216 h), the forgetting was observed; i.e., the
CR% of control-saline group significantly decreased. In contrast, SB-699551 at
0.3 and 3.0 mg/kg prevents forgetting. Additionally, as previously reported the
non-competitive NMDA receptor antagonist dizocilpine (0.2 mg/kg) or the non
selective cholinergic antagonist scopolamine (0.3 mg/kg) decreased CR in STM. SB
699551 (0.3 mg/kg) alone also produced amnesia-like effect. Co-administration of
SB-699551-dizocilpine or SB-699551-scopolamine reversed the SB-699551 induced
amnesic effects in LTM (24-h). Nose-poke seems to be a reliable operandum. The
anti-amnesic and anti-forgetting mechanisms of amnesic SB-699551-dose remain
unclear. The present findings are consistent with the notion that low doses of 5
HT5A receptor antagonists might be useful for reversing memory deficits
associated to forgetting and amnesia. Of course, further experiments are
necessary.
PMID- 29330005
TI - A Phase I Study of Irinotecan, Capecitabine (Xeloda), and Oxaliplatin in Patients
With Advanced Colorectal Cancer.
AB - BACKGROUND: The objective of the present phase I study was to define the dose
limiting toxicities (DLTs) and maximum tolerated dose (MTD) of irinotecan,
capecitabine, and oxaliplatin given in combination (IXO regimen) to patients with
previously untreated, unresectable advanced or metastatic colorectal cancer
(CRC). PATIENTS AND METHODS: Patients received oxaliplatin followed by irinotecan
as intravenous infusions on day 1, with oral capecitabine taken twice daily (BID)
on days 2 to 15 of a 3-week cycle. The dose ranges were explored as follows:
oxaliplatin, 75 to 120 mg/m2; irinotecan, 160 to 230 mg/m2; capecitabine, 750 to
1000 mg/m2 BID. Dose escalation was performed individually for each drug at each
dose level according to the type and severity of toxicity encountered in the
previous cohort. RESULTS: A total of 39 patients were enrolled at 7 dose levels
and the MTD. The recommended doses for phase II evaluation were oxaliplatin 100
mg/m2, irinotecan 160 mg/m2, and capecitabine 950 mg/m2 BID. Diarrhea and febrile
neutropenia were DLTs. Of the 39 enrolled patients, 26 (67%) had confirmed
objective responses. The median progression-free survival was 11 months, and the
median overall survival was 25 months. The survival rate at 5 years was 23%.
CONCLUSION: The IXO regimen has a manageable toxicity profile with promising
antitumor activity as first-line treatment of advanced and metastatic CRC.
PMID- 29330004
TI - Recovery of stress-impaired social behavior by an antagonist of the CRF binding
protein, CRF6-33, in the bed nucleus of the stria terminalis of male rats.
AB - Social stress is recognized to promote the development of neuropsychiatric and
mood disorders. Corticotropin releasing factor (CRF) is an important neuropeptide
activated by social stress, and it contributes to neural and behavioral
adaptations, as indicated by impaired social interactions and anhedonic effects.
Few studies have focused on the role of the CRF binding protein (CRFBP), a
component of the CRF system, and its activity in the bed nucleus of stria
terminalis (BNST), a limbic structure connecting amygdala and hypothalamus. In
this study, animals' preference for sweet solutions was examined as an index of
stress-induced anhedonic responses in Wistar rats subjected to four brief
intermittent episodes of social defeat. Next, social approach was assessed after
local infusions of the CRFBP antagonist, CRF fragment 6-33 (CRF6-33) into the
BNST. The experience of brief episodes of social defeat impaired social approach
behaviors in male rats. However, intra-BNST CRF6-33 infusions restored social
approach in stressed animals to the levels of non-stressed rats. CRF6-33 acted
selectively on social interaction and did not alter general exploration in nether
stressed nor non-stressed rats. These findings suggest that BNST CRFBP is
involved in the modulation of anxiety-like responses induced by social stress.
PMID- 29330006
TI - Cue and context conditioning to respiratory threat: Effects of suffocation fear
and implications for the etiology of panic disorder.
AB - Interoceptive threats play a crucial role in the etiology of panic disorder (PD).
While body sensations may become conditioned stimuli (CS) when paired with such
interoceptive threats (cue conditioning), the environment in which such
interoceptive threats occur may also be learned as a predictor of threat (context
conditioning). Suffocation fear (SF) might facilitate these associative learning
processes if threats of suffocation become relevant as unconditioned stimuli
(US). To investigate whether SF affects associative learning during such
respiratory threat, we used mild dyspnea as CS that predicted the occurrence of
strong dyspnea (US) in one context (predictable), was not related to the
occurrence of the US in another context (unpredictable) or was presented in a
different context (safe) in which no US was delivered. Startle eyeblink responses
and subjective reports were assessed in 34 participants during learning.
Individuals reporting high SF showed a clear potentiation of the startle response
during the interoceptive CS predicting the occurrence of interoceptive threat
(US). Such startle potentiation was not observed when the CS remained unpaired
(safe or unpredictable context). Moreover, high SF persons also showed a
significant startle potentiation to the threatening context, when the CS did not
predict the onset of the US. No such learning effects were observed for low SF
individuals. The data support the view that defensive response mobilization can
be triggered by cues but also by contexts that predict the occurrence of
interoceptive threats if these threats are relevant for the individuals,
supporting learning accounts for the development of PD.
PMID- 29330008
TI - Electrophysiological brain indices of risk behavior modification induced by
contingent feedback.
AB - The main aim of this research was to study the effects of response feedback on
risk behavior and the neural and cognitive mechanisms involved, as a function of
the feedback contingency. Sixty drivers were randomly assigned to one of three
feedback groups: contingent, non-contingent and no feedback. The participants'
task consisted of braking or not when confronted with a set of risky driving
situations, while their electroencephalographic activity was continuously
recorded. We observed that contingent feedback, as opposed to non-contingent
feedback, promoted changes in the response bias towards safer decisions. This
behavioral modification implied a higher demand on cognitive control, reflected
in a larger amplitude of the N400 component. Moreover, the contingent feedback,
being predictable and entailing more informative value, gave rise to smaller SPN
and larger FRN scores when compared with non-contingent feedback. Taken together,
these findings provide a new and complex insight into the neurophysiological
basis of the influence of feedback contingency on the processing of decision
making under risk. We suggest that response feedback, when contingent upon the
risky behavior, appears to improve the functionality of the brain mechanisms
involved in decision-making and can be a powerful tool for reducing the tendency
to choose risky options in risk-prone individuals.
PMID- 29330009
TI - The ALMANACH Project: Preliminary results and potentiality from Afghanistan.
AB - INTRODUCTION: ALMANACH (ALgorithms for the MANagement of Acute CHildhood
illnesses) is an electronic version of IMCI (Integrated Management of Childhood
Illness) running on tablets. ALMANACH enhances its concept, it integrates well
into health staff's daily consultation work and facilitates diagnosis and
treatment. ALMANACH informs when to refer a child or to perform a rapid
diagnostic test (RDT), recommends the right treatment dosage and synchronizes
collected data real time with a Health Management Information System (DHIS2) for
epidemiological evaluation and decision making. OBJECTIVES: Since May 2016,
ALMANACH is under investigational deployment in three primary health care
facilities in Afghanistan with the goal to improve the quality of care provided
to children between 2 months and 5 years old. METHODS: IMCI's algorithms were
updated in considering latest scientific publications, national guidelines,
innovations in RDTs, the target population's epidemiological profile and the
local resources available. Before the implementation of the project, a direct
observation of 599 consultations was carried out to assess the daily performance
at three selected health facilities in Kabul. RESULTS: The baseline survey showed
that nutritional screening, vitamin A supplementation and deworming were not
systematically performed: few patients were diagnosed for malnutrition (1.8%),
received vitamin A (2.7%) or deworming (7.5%). Physical examination was
appropriate only for 23.8% of the diagnoses of respiratory or gastrointestinal
diseases, ear infection and sore throat. Respiratory rate was checked only in
33.5% of the children with fever and cough, dehydration status was assessed in
only 16.5% of the diarrhoea cases. Forty-seven percent of patients received
incorrect treatment. Sixty-four percent of the children, before the introduction
of ALMANACH, received at least one antibiotic, although for 87.1% antibiotic
therapy was unnecessary. The review of 8'047 paediatric consultations between May
2016 and September 2017 showed that with ALMANACH, malnutrition detection,
deworming and Vitamin A supplementation increased respectively to 4.4%, 50.2% and
27.5%. Antibiotic prescription decreased to 21.83% and all children were examined
and treated in compliance with the protocols. CONCLUSION: A survey will be
conducted one year after the implementation to validate these initial promising
results. If the efficacy of the approach is confirmed, ALMANACH could establish
as a powerful innovation for primary health care.
PMID- 29330007
TI - Lost connections: Oxytocin and the neural, physiological, and behavioral
consequences of disrupted relationships.
AB - In humans and rodent animal models, the brain oxytocin system is paramount for
facilitating social bonds, from the formation and consequences of early-life
parent-infant bonds to adult pair bond relationships. In social species, oxytocin
also mediates the positive effects of healthy social bonds on the partners' well
being. However, new evidence suggests that the negative consequences of early
neglect or partner loss may be mediated by disruptions in the oxytocin system as
well. With a focus on oxytocin and its receptor, we review studies from humans
and animal models, i.e. mainly from the biparental, socially monogamous prairie
vole (Microtus ochrogaster), on the beneficial effects of positive social
relationships both between offspring and parents and in adult partners. The
abundance of social bonds and benevolent social relationships, in general, are
associated with protective effects against psycho- and physiopathology not only
in the developing infant, but also during adulthood. Furthermore, we discuss the
negative effects on well-being, emotionality and behavior, when these bonds are
diminished in quality or are disrupted, for example through parental neglect of
the young or the loss of the partner in adulthood. Strikingly, in prairie voles,
oxytocinergic signaling plays an important developmental role in the ability to
form bonds later in life in the face of early-life neglect, while disruption of
oxytocin signaling following partner loss results in the emergence of depressive
like behavior and physiology. This review demonstrates the translational value of
animal models for investigating the oxytocinergic mechanisms that underlie the
detrimental effects of developmental parental neglect and pair bond disruption,
encouraging future translationally relevant studies on this topic that is so
central to our daily lives.
PMID- 29330010
TI - Nasopharyngeal Lactobacillus is associated with a reduced risk of childhood
wheezing illnesses following acute respiratory syncytial virus infection in
infancy.
AB - BACKGROUND: Early life acute respiratory infection (ARI) with respiratory
syncytial virus (RSV) has been strongly associated with the development of
childhood wheezing illnesses, but the pathways underlying this association are
poorly understood. OBJECTIVE: To examine the role of the nasopharyngeal
microbiome in the development of childhood wheezing illnesses following RSV ARI
in infancy. METHODS: We conducted a nested cohort study of 118 previously
healthy, term infants with confirmed RSV ARI by RT-PCR. We used next-generation
sequencing of the V4 region of the 16S ribosomal RNA gene to characterize the
nasopharyngeal microbiome during RSV ARI. Our main outcome of interest was 2-year
subsequent wheeze. RESULTS: Of the 118 infants, 113 (95.8%) had 2-year outcome
data. Of these, 46 (40.7%) had parental report of subsequent wheeze. There was no
association between the overall taxonomic composition, diversity, and richness of
the nasopharyngeal microbiome during RSV ARI with the development of subsequent
wheeze. However, the nasopharyngeal detection and abundance of Lactobacillus was
consistently higher in infants who did not develop this outcome. Lactobacillus
also ranked first among the different genera in a model distinguishing infants
with and without subsequent wheeze. CONCLUSIONS: The nasopharyngeal detection and
increased abundance of Lactobacillus during RSV ARI in infancy are associated
with a reduced risk of childhood wheezing illnesses at age 2 years.
PMID- 29330012
TI - Basophil testing with CD63 in pollen-sensitized patients is independent of the
circadian clock.
PMID- 29330011
TI - Mutations in PI3K110delta cause impaired natural killer cell function partially
rescued by rapamycin treatment.
AB - BACKGROUND: Heterozygous gain-of-function mutations in PI3K110delta lead to
lymphadenopathy, lymphoid hyperplasia, EBV and cytomegalovirus viremia, and
sinopulmonary infections. OBJECTIVE: The known role of natural killer (NK) cell
function in the control of EBV and cytomegalovirus prompted us to investigate the
functional and phenotypic effects of PI3K110delta mutations on NK cell subsets
and cytotoxic function. METHODS: Mutations in patients were identified by using
whole-exome or targeted sequencing. We performed NK cell phenotyping and
functional analysis of patients' cells using flow cytometry, standard Cr51
cytotoxicity assays, and quantitative confocal microscopy. RESULTS: PI3K110delta
mutations led to an altered NK cell developmental phenotype and cytotoxic
dysfunction. Impaired NK cell cytotoxicity was due to decreased conjugate
formation with susceptible target cells and abrogated activation of cell
machinery required for target cell killing. These defects were restored partially
after initiation of treatment with rapamycin in 3 patients. CONCLUSION: We
describe novel NK cell functional deficiency caused by PI3K110delta mutation,
which is a likely contributor to the severe viremia observed in these patients.
Rapamycin treatment partially restores NK cell function, providing a further
rationale for its use in patients with this disease.
PMID- 29330014
TI - Frequency of red blood cell genotypes in multi-transfused patients and blood
donors from Minas Gerais, Southeast Brazil.
AB - BACKGROUND AND OBJECTIVES: The frequency of red blood cell (RBC) antigens in
Brazil varies due to differences in the ethnic groups in different regions;
however, these studies have not been performed in Minas Gerais, where African
admixture is more prevalent in comparison with other states. Due to these facts,
this study aimed to determine the frequency of RBC genotypes on Rh, Kell, Duffy
and Kidd systems in blood donors and multi-transfused patients from Minas Gerais,
Southeast Brazil. METHODS: Blood samples were collected from 170 donors and 117
patients with different diagnosis and at least three RBC transfusions. DNA was
extracted from leukocytes and genotyped by PCR-SSP, Multiplex or RFLP to alleles
of the referred systems. The results were compared by the Chi-Square test, with a
significance level of 5%. RESULTS: The most frequent genotypes were: RHD+,
RHCE*ce/RHCE*ce, KEL*2/KEL*2, FY*B-67T/FY*B-67T and JK*A/JK*B. FY*B-67C/FY*B-67C,
RHD*Psi and JK*A/JK*A genotypes were more prevalent in sickle cell disease (SCD)
patients than in donors. Many differences in RBC genotype frequencies were
observed in comparison with studies from other states and countries. CONCLUSION:
The results reinforce the importance of determining RBC genotypes of blood donors
and patients in different regions of Brazil and the world, improving the
transfusion safety of individuals requiring chronic RBC transfusions, especially
those with SCD, due to ethnic differences in relation to donors.
PMID- 29330013
TI - A functional splice variant associated with decreased asthma risk abolishes the
ability of gasdermin B to induce epithelial cell pyroptosis.
AB - BACKGROUND: Genetic variants in the chromosomal region 17q21 are consistently
associated with asthma. However, mechanistic studies have not yet linked any of
the associated variants to a function that could influence asthma, and as a
result, the identity of the asthma gene(s) remains elusive. OBJECTIVES: We sought
to identify and characterize functional variants in the 17q21 locus. METHODS: We
used the Exome Aggregation Consortium browser to identify coding (amino acid
changing) variants in the 17q21 locus. We obtained asthma association measures
for these variants in both the Genetic Epidemiology Research in Adult Health and
Aging (GERA) cohort (16,274 cases and 38,269 matched controls) and the EVE
Consortium study (5,303 asthma cases and 12,560 individuals). Gene expression and
protein localization were determined by quantitative RT-PCR and fluorescence
immunostaining, respectively. Molecular and cellular studies were performed to
determine the functional effects of coding variants. RESULTS: Two coding variants
(rs2305480 and rs11078928) of the gasdermin B (GSDMB) gene in the 17q21 locus
were associated with lower asthma risk in both GERA (odds ratio, 0.92; P = 1.01 *
10-6) and EVE (odds ratio, 0.85; joint PEVE = 1.31 * 10-13). In GERA, rs11078928
had a minor allele frequency (MAF) of 0.45 in unaffected (nonasthmatic) controls
and 0.43 in asthma cases. For European Americans in EVE, the MAF of rs2305480 was
0.45 for controls and 0.39 for cases; for all EVE subjects, the MAF was 0.32 for
controls and 0.27 for cases. GSDMB is highly expressed in differentiated airway
epithelial cells, including the ciliated cells. We found that, when the GSDMB
protein is cleaved by inflammatory caspase-1 to release its N-terminal fragment,
potent pyroptotic cell death is induced. The splice variant rs11078928 deletes
the entire exon 6, which encodes 13 amino acids in the critical N-terminus, and
abolishes the pyroptotic activity of the GSDMB protein. CONCLUSIONS: Our study
identified a functional asthma variant in the GSDMB gene of the 17q21 locus and
implicates GSDMB-mediated epithelial cell pyroptosis in pathogenesis.
PMID- 29330015
TI - Mother-to-child transmission of extended-spectrum-beta-lactamase-producing
Enterobacteriaceae.
AB - BACKGROUND: Preterm infants are at high risk for extended-spectrum-beta-lactamase
producing Enterobacteriaceae (ESBL-E) sepsis and neonatal intensive care unit
(NICU) outbreaks. Maternal colonization with ESBL-E may be precursory to mother
to-child transmission. However, there is no consensus regarding surveillance of
pregnant women for ESBL-E colonization. AIM: To identify pairs of mothers and
infants harbouring same-strain ESBL-E colonization and to determine whether
maternal transmission may play a role in increasing ESBL-E carriage in preterm
infants. METHODS: This was a one-year analysis from an ongoing, prospective ESBL
E surveillance of mothers of premature infants and their offspring. Mother-infant
pairs colonized with the same bacteria underwent strain analysis using pulsed
field gel electrophoresis (PFGE). Clinical parameters were collected from the
hospital computerized records. FINDINGS: Between January 2015 and January 2016,
313/409 (76.5%) mothers and all 478 (100%) infants were screened for ESBL-E
colonization; carriage rates were 21.5% and 14.8%, respectively. Four (5.6%)
colonized infants developed late-onset sepsis and two (2.8%) died. Twenty-five
mother-infant pairs colonized with the same bacterial strain were identified; a
subgroup of 10 pairs of isolates underwent PFGE, and 70% displayed an identical
PFGE fingerprint. No similarities were found between isolates recovered from
unrelated neonates and mothers. ESBL-E colonization was found significantly
earlier in infants of mothers colonized at birth (P<0.001) compared with infants
of non-colonized mothers. CONCLUSIONS: ESBL-E carriage rates in mothers and NICU
infants with non-negligible maternal-neonatal ESBL-E transmission in the study
region indicate that maternal colonization surveillance and/or further infection
control interventions should be considered.
PMID- 29330016
TI - Clinical impact of delayed catheter removal for patients with central-venous
catheter-related Gram-negative bacteraemia.
AB - BACKGROUND: Gram-negative bacteria are increasingly the cause of catheter-related
bloodstream infection (CRBSI), and the prevalence of multi-drug-resistant strains
is rising rapidly. This study evaluated the impact of delayed central venous
catheter (CVC) removal on clinical outcomes in patients with Gram-negative CRBSI.
METHODS: Between January 2007 and December 2016, patients with Gram-negative
bacteraemia and CVC placement, from two tertiary care hospitals, were included
retrospectively. Cases with CVC removal more than three days after onset of
bacteraemia or without CVC removal were classified as having delayed CVC removal.
RESULTS: In total, 112 patients were included. Of these, 78 had CRBSI (43
definite and 35 probable) and 34 had Gram-negative bacteraemia from another
source (non-CRBSI). Enterobacteriaceae were less common pathogens in patients
with CRBSI than in patients with non-CRBSI (11.5% vs 41.3%; P<0.001). Delayed CVC
removal was associated with increased 30-day mortality (40.5% vs 11.8%; P=0.01)
in patients with Gram-negative CRBSI; this was not seen in patients with non
CRBSI (25.0% vs 14.3%; P>0.99). Delayed CVC removal [odds ratio (OR) 6.8], multi
drug-resistant (MDR) Gram-negative bacteraemia (OR 6.3) and chronic renal failure
(OR 11.1) were associated with 30-day mortality in patients with CRBSI. The
protective effect of early CVC removal on mortality was evident in the MDR group
(48.3% vs 18.2%; P=0.03), but not in the non-MDR group (11.1% vs 0%; P=0.43).
CONCLUSION: CVCs should be removed early to improve clinical outcomes in patients
with Gram-negative CRBSI, especially in settings where MDR isolates are
prevalent.
PMID- 29330017
TI - A wrapped multi-label classifier for the automatic diagnosis and prognosis of
Alzheimer's disease.
AB - BACKGROUND: AD is the most frequent neurodegenerative disease, severely impacting
our society. Early diagnosis and prognosis are challenging tasks in the
management of AD patients. NEW METHOD: We implemented a machine-learning
classifier for the automatic early diagnosis and prognosis of AD by means of
features extracted, selected and optimized from structural MRI brain images. The
classifier was designed to perform multi-label automatic classification into the
following four classes: HC, ncMCI, cMCI, and AD. RESULTS: From our analyses, it
emerged that MMSE and hippocampus-related measures must be included as primary
measures in automatic-classification systems for both the early diagnosis and the
prognosis of AD. The voting scheme mainly based on the binary-classification
performances on the different four groups is the best choice to model the multi
label decision function for AD, when compared with a simple majority-vote scheme
or with a scheme aimed at discriminating patients with high vs low risk of
conversion to AD and therapy addressing. COMPARISON WITH EXISTING METHOD(S): The
accuracies of our binary classifications were higher than or comparable to
previously published methods. An improvement is needed on the approach we used to
combine binary-classification outputs to obtain the final multi-label
classification. CONCLUSIONS: The performance of multi-label automatic
classification systems strongly depends on the choice of the voting scheme used
for combining binary-classification labels.
PMID- 29330018
TI - Testicular adrenal rest tumor screening and fertility counseling among males with
congenital adrenal hyperplasia.
AB - BACKGROUND: Reduced fertility is a common potential problem among males with
congenital adrenal hyperplasia (CAH), with nearly half experiencing impaired
sperm production. The major cause of oligo/azoospermia in CAH is testicular
adrenal rest tumors (TARTs). Studies indicate that ultrasound screening for TARTs
should begin during childhood, yet it remains unclear whether boys with CAH are
routinely screened for TARTs and/or counseled about infertility risk and
potential interventions such as fertility testing and/or preservation. OBJECTIVE:
The purpose of this study was to examine TART screening and fertility counseling
practices among boys with CAH. STUDY DESIGN: An IRB-approved retrospective chart
review was conducted of all males with ICD-9/10 codes for CAH (2007-2016) at a
large pediatric academic center to examine: age and indication for diagnosis; age
at first and last documented pediatric endocrinology and urology visit; history
of ultrasound examinations; and documentation of fertility counseling. RESULTS:
Forty-six patients were included, of whom 38 had 21-hydroxylase deficiency.
Median age at diagnosis was 2 weeks (range 7 days-10 years). Median age at the
most recent pediatric endocrinology clinic visit was 14 years (range 2-42 years).
Twenty-nine patients were >11 years old (63% of the sample) at the time of the
study and 14 of these were >18 years old (30% of the sample). Seven patients
(15%) had a screening ultrasound at some point in their care, of whom three had
TARTs. Fertility was mentioned in the records of six subjects (13% of the
sample). Six of the subjects (13%) had any mention of fertility in their records.
None of the patients had biochemical testing or semen analysis to assess gonadal
function, and none were offered fertility preservation. Only one patient was seen
by a pediatric urologist. DISCUSSION: Despite the limitations of a single-center
retrospective design, our findings highlight that TART screening and fertility
counseling remain underutilized in boys with CAH. There is a need for increased
awareness and development of practice guidelines within pediatric urology and
endocrinology to address this common and understudied problem. CONCLUSION: In
addition to a screening ultrasound in puberty and consideration of semen analysis
after puberty, these boys may benefit from seeing a pediatric urologist
independently or in an interdisciplinary program. Boys with CAH and their
families should be educated about infertility risk and potential interventions,
with the goal of improving reproductive outcomes in this population.
PMID- 29330019
TI - Parental decisional regret and views about optimal timing of female genital
restoration surgery in congenital adrenal hyperplasia.
AB - PURPOSE: The role of female genital restoration surgery (FGRS) in girls with
congenital adrenal hyperplasia (CAH) is controversial, with no long-term parent
reported outcomes available. Decisional regret (DR) affects most parents after
their children's treatment of pediatric conditions, including hypospadias. We
aimed to assess parental DR after FGRS in infancy or toddlerhood and explore
optimal timing for surgery. MATERIALS AND METHODS: One-hundred and six parents of
females with CAH undergoing FGRS before 3 years old and followed at our
institution (1999-2017) were invited to enroll online. Higher Decision Regret
Scale (DRS) scores indicated greater DR (range 0-100). Participants also reported
preferred FGRS timing relative to their surgery (earlier, same, later/delayed).
Non-parametric statistical tests were used. RESULTS: Thirty-nine parents (median
4.4 years after FGRS) participated (36.8% response rate). Median age at FGRS was
9 months. Median DRS score was 0 (mean: 5.0). Overall, 20.5% of parents reported
some regret (all mild-moderate) (Figure). Fewer parents reported DR after FGRS
compared with published DR after hypospadias repair (50-92%, p <= 0.001) or
adenotonsillectomy (41-45%, p <= 0.03). No parent preferred delayed FGRS. Seven
parents (18.1%) preferred earlier surgery, especially when performed after
birthday (80.0% vs. 8.8%, p = 0.004). DISCUSSION: We present the first report of
validated long-term parent-reported outcomes after FGRS in infant and toddler
girls with CAH. One limitation is that this is largely a single surgeon series.
Reasons for the observed low levels of DR are likely multifactorial. Far from a
definitive study, we aimed to provide parents willing to share about their
experience an opportunity to do so. For that reason, selection bias may exist in
our study. While parents with higher DR were potentially less likely to
participate because of mistrust of the medical establishment, those with a
negative experience may in fact be more likely to voice their opinions. A low
participation rate was likely a result of the sensitive nature of FGRS, a desire
for privacy, and inability to locate parents. A larger study will be required to
assess how DR is affected by sexual function, genital appearance and
complications, and DR among women with CAH. CONCLUSIONS: Parents of females with
CAH report low levels of DR after FGRS in infancy and toddlerhood. This appears
to be lower than after other genital and non-genital pediatric procedures. When
present, parental DR is usually mild. No parents preferred delayed surgery, even
among those with DR. Some preferred earlier surgery.
PMID- 29330020
TI - Predictors of deep brain stimulation outcome in tremor patients.
AB - BACKGROUND: Deep brain stimulation of the ventro-intermedius nucleus of the
thalamus is an established treatment for tremor of differing etiologies but
factors that may predict the short- and especially long-term outcome of surgery
are still largely unknown. METHODS: We retrospectively investigated the clinical,
pharmacological, electrophysiological and anatomical features that might predict
the initial response and preservation of benefit in all patients who underwent
deep brain stimulation for tremor. Data were collected at the following time
points: baseline (preoperative), one-year post-surgery, and most recent visit.
Tremor severity was recorded using the Fahn-Tolosa-Marin Tremor Rating Scale
and/or the Unified Parkinson's Disease Rating Scale. RESULTS: A total of 52
patients were included in the final analysis: 31 with essential tremor, 15 with
cerebellar tremor of different etiologies, and 6 with Parkinson's disease. Long
term success (mean follow-up duration 34.7 months, range 1.7-121.1 months) was
reported in 63.5%. Predictors of long-term benefit were: underlying tremor
etiology (best outcome in Parkinson's disease, worst outcome in cerebellar
tremor); age at surgery (the older the better); baseline tremor severity (the
greater the better); lack of response to benzodiazepines; a more anterior
electrode placement and single-unit beta power (the greater the better).
CONCLUSIONS: Specific patients' features (including single unit beta activity)
and electrode locations may predict the short- and long-term benefit of thalamic
stimulation for tremor. Future prospective studies enrolling a much larger sample
of patients are needed to substantiate the associations detected by this
retrospective study.
PMID- 29330022
TI - Extracellular matrix contribution to skin wound re-epithelialization.
AB - The ability of skin to act as a barrier is primarily determined by cells that
maintain the continuity and integrity of skin and restore it after injury.
Cutaneous wound healing in adult mammals is a complex multi-step process that
involves overlapping stages of blood clot formation, inflammation, re
epithelialization, granulation tissue formation, neovascularization, and
remodeling. Under favorable conditions, epidermal regeneration begins within
hours after injury and takes several days until the epithelial surface is intact
due to reorganization of the basement membrane. Regeneration relies on numerous
signaling cues and on multiple cellular processes that take place both within the
epidermis and in other participating tissues. A variety of modulators are
involved, including growth factors, cytokines, matrix metalloproteinases,
cellular receptors, and extracellular matrix components. Here we focus on the
involvement of the extracellular matrix proteins that impact epidermal
regeneration during wound healing.
PMID- 29330021
TI - CCN4/WISP1 controls cutaneous wound healing by modulating proliferation,
migration and ECM expression in dermal fibroblasts via alpha5beta1 and TNFalpha.
AB - Understanding the mechanisms that control cutaneous wound healing is crucial to
successfully manage repair of damaged skin. The goal of the current study was to
uncover novel extracellular matrix (ECM) components that control the wound
healing process. Full thickness skin defects were created in mice and used to
show CCN4 up-regulation during wound-healing as early as 1 day after surgery,
suggesting a role in inflammation and subsequent dermal migration and
proliferation. To determine how CCN4 could regulate wound healing we used Ccn4-KO
mice and showed they had delayed wound closure accompanied by reduced expression
of Col1a1 and Fn mRNA. Boyden chamber assays using Ccn4-deficient dermal
fibroblasts showed they have reduced migration and proliferation compared to WT
counterparts. To confirm CCN4 has a role in proliferation and migration of dermal
cells, siRNA knockdown and transduction of CCN4 adenoviral transduction were used
and resulted in reduced or enhanced migration of human adult dermal fibroblast
(hADF) cells respectively. The induced migration of the dermal fibroblasts by
CCN4 appears to work via alpha5beta1 integrin receptors that further stimulates
down-stream ERK/JNK signaling. The regulation of CCN4 by TNF-alpha prompted us
look further at their potential relationship. Treatment of hADFs with CCN4 and
TNF-alpha alone or together showed CCN4 counteracted the inhibition of TNF-alpha
on COL1A1 and FN mRNA expression and the stimulation of TNF-alpha on MMP-1 and
MMP3 mRNA expression. CCN4 appeared to counterbalance the effects of TNF-alpha by
inhibiting downstream NF-kappaB/p-65 signaling. Taken together we show CCN4
stimulates dermal fibroblast cell migration, proliferation and inhibits TNF-alpha
stimulation, all of which could regulate wound healing.
PMID- 29330023
TI - Unraveling the differential structural stability and dynamics features of T7
endolysin partially folded conformations.
AB - BACKGROUND: Characterization of partially collapsed protein conformations at
atomic level is a daunting task due to their inherent flexibility and
conformational heterogeneity. T7 bacteriophage endolysin (T7L) is a single-domain
amidase that facilitates the lysis of Gram-negative bacteria. T7L exhibits a pH
dependent structural transition from native state to partially folded (PF)
conformation. In the pH range 5-3, T7L PF states display differential ANS binding
characteristics. METHODS: CD, fluorescence, NMR spectroscopy and lysis assays
were used to investigate the structure-stability- dynamics relationships of T7L
PF conformations. RESULTS: Structural studies indicated a partial loss of
secondary/tertiary structures compared to its native state. The loss in the
tertiary structure and the hydrophobic core opening increases upon decrease of pH
from 5 to 3. Thermal denaturation experiments delineated that the pH 5
conformation is thermally irreversible in contrast to pH 3, depicting that
hydrophobic core opening is essential for thermal reversibility. Further, urea
dependent unfolding features of PF state at pH 5 and 4 evidenced for a collapsed
conformation at intermediate urea concentrations. Residue level studies revealed
that alpha1-helix and beta3-beta4 segment of T7L are the major contributors for
such a structural collapse and inherent dynamics. CONCLUSIONS: The results
suggested that the low pH PF states of T7L are heterogeneous and exhibits
differential structural, unfolding, thermal reversibility, and dynamic features.
GENERAL SIGNIFICANCE: Unraveling the structure-stability characteristics of
different endolysin conformations is essential for designing novel chimeric and
engineered phage endolysins as broadband antimicrobial agents over a varied pH
range.
PMID- 29330025
TI - The role of extracellular and intracellular Nicotinamide phosphoribosyl
transferase in cancer: Diagnostic and therapeutic perspectives and challenges.
AB - Nicotinamide phosphoribosyl-transferase (Nampt) or pre-B cell colony-enhancing
factor or visfatin represents a pleiotropic molecule acting as an enzyme, a
cytokine and a growth factor. Intracellular Nampt plays an important role in
cellular bioenergetics and metabolism, particularly NAD biosynthesis. NAD
biosynthesis is critical in DNA repair, oncogenic signal transduction,
transcription, genomic integrity and apoptosis. Although its insulin-mimetic
function remains a controversial issue, extracellular Nampt presents
proliferative, anti-apoptotic, pro-inflammatory, pro-angiogenic and metastatic
properties. Nampt is upregulated in many malignancies, including obesity
associated cancers, and is associated with worse prognosis. Serum Nampt may be a
potential diagnostic and prognostic biomarker in cancer. Pharmacologic agents
that neutralize Nampt or medications that decrease Nampt levels or downregulate
signaling pathways downstream of Nampt may prove to be useful anti-cancer
treatments. In particular, Nampt inhibitors as monotherapy or in combination
therapy have displayed anti-cancer activity in vivo and in vitro. The aim of this
review is to explore the role of Nampt in cancer pathophysiology as well as to
synopsize the mechanisms underlying the association between extracellular and
intracellular Nampt, and malignancy. Exploring the interplay of cellular
bioenergetics, inflammation and adiposopathy is expected to be of importance in
the development of preventive and therapeutic strategies against cancer.
PMID- 29330024
TI - Nucleophosmin-1 regions associated with acute myeloid leukemia interact
differently with lipid membranes.
PMID- 29330026
TI - Sound shock response in larval zebrafish: A convenient and high-throughput
assessment of auditory function.
AB - Given that hearing ability can be challenged in diverse ways, it is necessary to
develop an easily conducted, high-throughput method for assessing potential
auditory risks. Measuring the acoustic startle response (ASR) has become a
critical behavioral method in hearing research using zebrafish (Danio rerio). In
this study, changes in the activity of zebrafish larvae (10 days post
fertilization (dpf)) due to exposure to a sudden easily-generated broad-band
noise were automatically and objectively recorded and analyzed without building
sophisticated equipments. A significant increase in activity was induced by the
noise stimulation and the alterations were impaired by gentamicin. In addition, a
clear dose-response trend was observed between gentamicin exposure and the
impaired activity, and a similar phenomenon was observed between gentamicin
exposure and damage to hair cells. Our results suggested that alterations in the
activity induced by a broad-band noise can potentially be used as an efficient
assay for assessing hearing ability.
PMID- 29330027
TI - Selective estrogen receptor modulator ormeloxifene suppresses embryo implantation
via inducing miR-140 and targeting insulin-like growth factor 1 receptor in rat
uterus.
AB - Ormeloxifene, the non-steroidal SERM contraceptive, inhibits endometrial
receptivity and embryo implantation via countering nidatory estrogen. However,
the molecular mechanism of ormeloxifene action responsible for its contraceptive
efficacy still remains unclear. Herein, we aimed to identify the miRNAs modulated
under the influence of ormeloxifene and to explore their role in endometrial
receptivity and embryo implantation. By doing microRNA sequencing analysis, a
total of 168 miRNAs were found to be differentially expressed in uterine tissue
of ormeloxifene-treated rats, on day 5 (10:00 h) of pregnancy i.e. peri
implantation period. Out of differentially expressed miRNAs, miR-140 expression
was found to be elevated in ormeloxifene administered groups and was selected for
detailed investigation. In-vivo gain-of-function of miR-140 resulted in a
significant reduction of implantation sites indicating its role in embryo
implantation. The experiment on delayed implantation showed that estradiol caused
down-regulation of miR-140. It also suppressed the attachment and outgrowth of
BeWo spheroids to RL95-2 endometrial cells. In transwell migration assay, miR-140
was found to be involved in suppression of migration and invasion of endometrial
epithelial cells. The ormeloxifene treatment caused up-regulation of miR-140
along with down-regulated expression of its target IGF1R in endometrial
epithelial and stromal cells which also led to the suppression of downstream
effectors integrin beta3 and FAK. In mimic miR-140 receiving horn, the reduced
expression of IGF1R was observed along with suppressed downstream integrin beta3
and FAK similar to that observed in uteri of ormeloxifene- treated rats. Taken
together, these findings suggest that ormeloxifene-induced inhibition of embryo
implantation occurs via inducing miR-140 and altering its target IGF1R in rat
uterus.
PMID- 29330028
TI - Perceptions of the relative harmfulness of marijuana and alcohol among adults in
Oregon.
AB - This study documents perceptions of the relative harmfulness of marijuana and
alcohol to a person's health among adults in Oregon just before the first legal
sales of marijuana for recreational use. We surveyed 1941 adults in Oregon in
September 2015. Respondents were recruited using an address-based sampling (ABS)
frame (n = 1314) and social media advertising (n = 627). Respondents completed
paper surveys (ABS-mail, n = 388) or online surveys (ABS-online, n = 926; social
media, n = 627). We used descriptive statistics and logistic regression models to
examine perceptions of the relative harmfulness of marijuana and alcohol by
sample characteristics, including substance use. About half of adults in Oregon
(52.5%) considered alcohol to be more harmful to a person's health than
marijuana. A substantial proportion considered the substances equally harmful
(40.0%). Few considered marijuana to be more harmful than alcohol (7.5%). In
general, respondents who were younger, male, and not Republican were more likely
than others to consider alcohol more harmful than marijuana. Respondents who were
older, female, and Republican were more likely to consider marijuana and alcohol
equally harmful. Most individuals who reported using both marijuana and alcohol
(67.7%) and approximately half of those who used neither substance (48.2%)
considered alcohol to be more harmful than marijuana. Perceptions about the
relative harmfulness of marijuana and alcohol may have implications for public
health. As state lawmakers develop policies to regulate marijuana, it may be
helpful to consider the ways in which those policies may also affect use of
alcohol and co-use of alcohol and marijuana.
PMID- 29330029
TI - Association of 100% fruit juice consumption and 3-year weight change among
postmenopausal women in the in the Women's Health Initiative.
AB - The association between drinking 100% fruit juice and long-term weight gain is
controversial and has been investigated in few studies. We examined whether 100%
fruit juice consumption was associated with weight change in a large prospective
cohort of postmenopausal women. We analyzed data from 49,106 postmenopausal women
in the United States enrolled in the Women's Health Initiative between 1993 and
1998. Food frequency questionnaires at baseline and year 3 assessed food and
beverage intake. Body weight was measured at in-person clinic visits. We used
linear mixed effects modeling to determine the association between change in 100%
fruit juice consumption and 3-year weight change over the same time period.
Covariates of interest included age, demographic factors, smoking, body mass
index, hormone replacement therapy, lifestyle factors, change in whole fruit
intake, and change in sugar-sweetened beverage intake. The mean weight change was
3.2 lbs. over 3 years. In multivariable adjusted analyses, each 1 serving/day
increase in 100% fruit juice intake was associated with a 3-year weight gain of
0.39 lbs. (95% confidence interval: 0.10, 0.69). In conclusion, an increase in
100% fruit juice consumption was associated with a small amount of long-term
weight gain in postmenopausal women.
PMID- 29330030
TI - Health impact assessment of cycling network expansions in European cities.
AB - We conducted a health impact assessment (HIA) of cycling network expansions in
seven European cities. We modeled the association between cycling network length
and cycling mode share and estimated health impacts of the expansion of cycling
networks. First, we performed a non-linear least square regression to assess the
relationship between cycling network length and cycling mode share for 167
European cities. Second, we conducted a quantitative HIA for the seven cities of
different scenarios (S) assessing how an expansion of the cycling network [i.e.
10% (S1); 50% (S2); 100% (S3), and all-streets (S4)] would lead to an increase in
cycling mode share and estimated mortality impacts thereof. We quantified
mortality impacts for changes in physical activity, air pollution and traffic
incidents. Third, we conducted a cost-benefit analysis. The cycling network
length was associated with a cycling mode share of up to 24.7% in European
cities. The all-streets scenario (S4) produced greatest benefits through
increases in cycling for London with 1,210 premature deaths (95% CI: 447-1,972)
avoidable annually, followed by Rome (433; 95% CI: 170-695), Barcelona (248; 95%
CI: 86-410), Vienna (146; 95% CI: 40-252), Zurich (58; 95% CI: 16-100) and
Antwerp (7; 95% CI: 3-11). The largest cost-benefit ratios were found for the 10%
increase in cycling networks (S1). If all 167 European cities achieved a cycling
mode share of 24.7% over 10,000 premature deaths could be avoided annually. In
European cities, expansions of cycling networks were associated with increases in
cycling and estimated to provide health and economic benefits.
PMID- 29330031
TI - Mental health disorders mediate association of sexual minority identity with
cardiovascular disease.
AB - BACKGROUND: Little is known about cardiovascular health disparities for lesbian,
gay, or bisexual (LGB) persons and whether these disparities are mediated by
mental health disorders due to sexual minority stress. We hypothesize LGB
identity is associated with an increased risk of cardiovascular disease (CVD) and
that major depressive disorder (MDD) and generalized anxiety disorders (GAD) may
mediate this association. METHODS: The National Epidemiologic Survey on Alcohol
and Related Conditions is a longitudinal, nationally-representative study of non
institutionalized U.S. adults. We cross-sectionally analyzed the second wave data
(2004-2005) comparing 577 self-identified LGB persons to 33,598 heterosexuals.
Multiple logistic regression modeling and mediation analysis (the product of
coefficients approach) were performed. RESULTS: LGB persons had significantly
higher CVD prevalence [adjusted odds ratio (AOR): 1.5, 95% CI: 1.2-1.9], and were
more likely to be diagnosed with MDD (AOR: 1.9, 1.8-2.1), GAD (AOR: 2.2, 1.9
2.4), or co-occurring MDD and GAD (AOR: 2.2, 2.0-2.5). MDD, GAD, and co
occurrence of MDD and GAD significantly mediated 14.3%, 22.2%, and 33.3% of the
association of LGB status with increased CVD prevalence, respectively.
CONCLUSIONS: Our findings identified a 50% increased CVD prevalence among LGB
persons and this increased risk was mediated in part by MDD and GAD, both being
more prevalent in sexual minority adults.
PMID- 29330032
TI - A free sugars daily value (DV) identifies more "less healthy" prepackaged foods
and beverages than a total sugars DV.
AB - Regulatory changes in Canada will require food labels to have a benchmark [%
Daily Value, %DV] for total sugars, based on 100 g/day, while US labels will
require a %DV for added sugars, based on 50 g/day. The objective of this study
was to compare two labelling policies, a total sugars DV (100 g/day) and a free
sugars DV (50 g/day) on food labels. This cross-sectional analysis of the Food
Label Information Program database focussed on top sources of total sugars intake
in Canada (n = 6924 foods). Products were categorized as "less healthy" using two
sets of criteria: a) free sugars levels exceeding the WHO guidelines (>=10%
energy from free sugars); and b) exceeding healthfulness cut-offs of the Food
Standards Australia New Zealand Nutrient Profiling Scoring Criterion (FSANZ
NPSC). The proportion of "less healthy" products with >=15%DV (defined as "a lot"
of sugars i.e. high in sugars, based on Health Canada's %DV labelling footnote
and educational message for dietary guidance) were compared for each sugar
labelling scenario. The free sugars DV showed better alignment with both methods
for assessing "healthfulness" than the total sugars DV. The free sugars DV
identified a greater proportion of "less healthy" foods with >=15%DV, based on
both the FSANZ-NPSC (70% vs. 45%, p < .0001) and WHO guidelines (82% vs. 55%, p <
.0001); particularly in sweet baked goods, sugars and preserves, chocolate bars,
confectionery, and frozen desserts categories. Compared to total sugars DV
labelling, using a free sugars DV identified more "less healthy" foods. Findings
support the adoption of free sugars labelling.
PMID- 29330033
TI - Service quality and parents' willingness to get adolescents HPV vaccine from
pharmacists.
AB - We sought to examine whether pharmacy service quality was associated with
parents' willingness to have immunizing pharmacists administer human
papillomavirus (HPV) vaccine to their adolescent children. Participants were a
national sample of 1504 US parents of adolescents ages 11 to 17 who completed an
online survey in 2014. Analyses used structural equation modeling. Parents rated
service quality and feelings of satisfaction with their pharmacies as moderate to
high. Many (44%) were willing to get HPV vaccine from immunizing pharmacists for
their adolescent children. Compared with parents who went to chain pharmacies,
parents who went to independent pharmacies gave higher ratings of service quality
(professionalism, confidentiality, milieu, all p < .001). Parents who went to
clinic pharmacies, compared with parents who went to chain pharmacies gave lower
ratings for milieu (p < .01). Parents who went to independent pharmacies had
lower willingness to get HPV vaccine from pharmacists compared to parents who
went to chain pharmacies (p = .001), but there was no difference in willingness
for parents who went to clinic versus chain pharmacies. Service quality and
satisfaction partially mediated the effect between independent pharmacies
compared to chain pharmacies and willingness (p < .05). Parents who knew their
pharmacists or expressed more confidence in HPV vaccine also had higher
willingness to get their children HPV vaccine from pharmacist. Many parents were
willing to go to immunizing pharmacists for their children's HPV vaccination.
Pharmacies that are considering offering HPV vaccine may be able to improve
vaccine uptake by increasing perception of service quality.
PMID- 29330034
TI - Successful treatment of a penicillin-intermediate and ceftriaxone-resistant
Granulicatella adiacens presumed prosthetic valve endocarditis with vancomycin.
AB - Advancements in rapid diagnostics have helped to identify nutritionally variant
streptococci (NVS) as an increasing cause of infective endocarditis (IE). This
case report highlights the challenges in susceptibility testing and the
importance of appropriate empiric treatment for Granulicatella adiacens, and
provides considerations for future practice guideline recommendations. Guidelines
for treatment of IE caused by NVS are currently limited to patients with native
valve disease. We present a patient with presumed prosthetic valve endocarditis
caused by G. adiacens, with clinically relevant resistance to recommended first
line agents (penicillin and ceftriaxone), who was successfully treated with 8
weeks of intravenous (IV) vancomycin. Vancomycin is currently recommended as an
alternate therapy for patients intolerant of penicillins, but we believe
vancomycin should be considered a first-line empiric treatment option for IE when
the identified organism is G. adiacens and susceptibility testing is not readily
available.
PMID- 29330036
TI - Regulation of fibrotic changes by the synergistic effects of cytokines,
dimensionality and matrix: Towards the development of an in vitro human dermal
hypertrophic scar model.
AB - : Current therapeutic strategies to reduce scarring in full thickness skin defect
offer limited success due to poor understanding of scar tissue formation and the
underlying signaling pathways. There is an urgent need to develop human cell
based in vitro scar tissue models as animal testing is associated with ethical
and logistic complications and inter-species variations. Pro-inflammatory
cytokines play critical role in regulating scar development through complex
interplay and interaction with the ECM and corresponding signaling pathways. In
this context, we assessed the responses of cultured fibroblasts with respect to
their differentiation into myofibroblasts using optimised cytokines (TGF-beta1,
IL-6 and IL-8) for scar formation in 2D (tissue culture plate, collagen type I
coated plate) vs 3D collagen type I gel based constructs. We attempted to deduce
the role of dimensionality of cell culture matrix in modulating differentiation,
function and phenotype of cultured fibroblasts. Validation of the developed model
showed similarity to etiology and pathophysiology of in vivo hypertrophic scar
with respect to several features: 1) transition of fibroblasts to myofibroblasts
with convincing expression of alpha-SMA stress fibers; 2) contraction; 3)
excessive collagen and fibronectin secretion; 4) expression of fibrotic ECM
proteins (SPARC and Tenascin); 5) low MMP secretion. Most importantly, we
elucidated the involvement of TGF-beta/SMAD and Wnt/beta-catenin pathways in
developing in vitro dermal scar. Hence, this relatively simple in vitro human
scar tissue equivalent may serve as an alternative for testing and designing of
novel therapeutics and help in extending our understanding of the complex
interplay of cytokines and related dermal scar specific signaling. STATEMENT OF
SIGNIFICANCE: Scarring of the skin affects almost millions of people per year in
the developed world alone, nevertheless the complex pathophysiology and the
precise signaling mechanisms responsible for this phenomenon of skin scarring are
still unknown. A number of anti-scar drugs are being developed and being tested
on animals and monolayer models. However, testing the efficacy of these drugs on
lab based 3D in vitro models may prove extremely useful in recapitulating the 3D
microenvironment of the native scar tissue. In that context in this study we have
demonstrated the development of 3D in vitro dermal scar model, by optimizing a
constellation of factors, such as combination of cytokines (TGF-beta1,IL-6,IL-8)
and cellular dimensionality in inducing the differentiation of dermal fibroblasts
to myofibroblasts. This in vitro scar model was successful in replicating
hallmark features of hypertrophic scar such as excessive synthesis of fibrotic
extracellular matrix, perturbed matrix homeostasis, contraction, diminished MMP
synthesis. The study also highlighted significant involvement of TGF-beta/SMAD
and Wnt/beta-catenin signaling pathways in in vitro scar formation.
PMID- 29330035
TI - Harmine enhances GABAergic transmission onto basoamygdala projection neurons in
mice.
AB - Emerging evidence indicates that loss of inhibitory tone in amygdala with its
subsequent overactivation contributes to the development of multiple mental
disorders such as anxiety disorders and post-traumatic stress disorder (PTSD).
Harmine is a member of natural beta-carboline alkaloids which can readily cross
the blood brain barrier and displays significant antidepressant and anxiolytic
effects in rodents. However, the underlying neurobiological mechanisms are
largely unknown. Here, by using whole-cell patch clamp recordings in in vitro
amygdala slices, we examined the effect of harmine on glutamatergic and GABAergic
transmission onto basal amygdala (BA) projection neurons (PNs). Our results
showed that harmine affected neither the amplitude nor the frequency of
spontaneous and miniature excitatory postsynaptic currents (sEPSCs/mEPSCs) of
PNs. By contrast, it markedly increased both the amplitude and frequency of the
spontaneous inhibitory postsynaptic currents (sIPSCs). For mIPSCs, only an
increase of their frequency but not amplitude was observed following harmine
perfusion, suggesting that harmine might act through presynaptic mechanism. In
parallel, a reduction of paired-pulse ratio of evoked IPSCs emerged in the
presence of harmine. Furthermore, the intrinsic excitability of PNs was
dramatically decreased upon harmine treatment. Together, our study suggests that
harmine selectively potentiates the inhibitory but not excitatory transmission
onto BA PNs, which may contribute to its antidepressant and anxiolytic influence.
PMID- 29330037
TI - Sustained delivery of glial cell-derived neurotrophic factors in collagen
conduits for facial nerve regeneration.
AB - : Facial nerve injury caused by traffic accidents or operations may reduce the
quality of life in patients, and recovery following the injury presents unique
clinical challenges. Glial cell-derived neurotrophic factor (GDNF) is important
in nerve regeneration; however, soluble GDNF rapidly diffuses into body fluids,
making it difficult to achieve therapeutic efficacy. In this work, we developed a
rat tail derived collagen conduit to connect nerve defects in a simple and safe
manner. GDNF was immobilized in the collagen conduits via chemical conjugation to
enable controlled release of GDNF. The GDNF delivery system prevented rapid
diffusion from the site without impacting bioactivity of GDNF; degradation of the
collagen conduit was inhibited owing to the chemical conjugation. The artificial
nerve conduit was then used to examine facial nerve regeneration across a facial
nerve defect. Following transplantation, the artificial nerve conduits degraded
gradually without causing dislocations and serious inflammation, with good
integration into the host tissue. Functional and histological tests indicated
that the artificial nerve conduits were able to guide the axons to grow through
the defect, reaching the distal stumps. The degree of nerve regeneration in the
group that was treated with the artificial nerve conduit approached that of the
autograft group, and exceeded that of the other conduit grafted groups. STATEMENT
OF SIGNIFICANCE: In this study, we developed artificial nerve conduits consisting
of GDNF immobilized on collagen, with the aim of providing an environment for
nerve regeneration. Our results show that the artificial nerve conduits guided
the regeneration of axons to the distal nerve segment. GDNF was immobilized
stably in the artificial nerve conduits, and therefore retained a sufficient
concentration at the target site to effectively promote the regeneration process.
The artificial nerve conduits exhibited good biocompatibility and facilitated
nerve regeneration and functional recovery with an efficacy that was close to
that of an autograft, and better than that of the other conduit grafted groups.
Our approach provides an effective delivery system that overcomes the rapid
diffusion of GDNF in body fluids, promoting peripheral nerve regeneration. The
artificial nerve conduit therefore qualifies as a putative candidate material for
the fabrication of peripheral nerve reconstruction devices.
PMID- 29330038
TI - Asthmatic/wheezing phenotypes in preschool children: Influential factors, health
care and urban-rural differences.
AB - BACKGROUND: Different wheezing and asthmatic phenotypes turned out to indicate
differences in etiology, risk factors and health care. We examined influential
factors and urban-rural differences for different phenotypes. METHODS: Parents of
4732 children filled out a questionnaire concerning children's health and
environmental factors administered within the Health Monitoring Units (GME) in a
cross-sectional study in Bavaria, Germany (2014/2015). To classify respiratory
symptoms, five phenotype groups were built: episodic, unremitting and frequent
wheeze, ISAAC (International Study of Asthma and Allergies in Children) - asthma
and physician-diagnosed asthma (neither of the groups are mutually exclusive).
For each phenotype, health care variables were presented and stratified for
residence. Urban-rural differences were tested by Pearson's chi-squared tests.
Multivariable logistic regression was performed to analyze associations between
influential factors and belonging to a phenotype group, and to compare groups
with regard to health care variables as outcome. RESULTS: Risk factors for
wheezing phenotypes were male gender (OR = 2.02, 95%-CI = [1.65-2.48]), having
older siblings (OR = 1.24, 95%-CI = [1.02-1.51]), and preterm delivery (OR =
1.61, 95%-CI = [1.13-2.29]) (ORs for unremitting wheeze). 57% of children with
ISAAC asthma and 74% with physician-diagnosed asthma had performed allergy tests.
Medication intake among all groups was more frequent in rural areas, and
physician's asthma diagnoses were more frequent in urban areas. CONCLUSIONS: In
accordance with previous research this study confirms that male gender, older
siblings and preterm delivery are associated with several wheezing phenotypes.
Overall, low numbers of allergy tests among children with physician's diagnoses
highlight a discrepancy between common practice and current knowledge and
guidelines. Residential differences in health care might encourage further
research and interventions strategies.
PMID- 29330039
TI - Age as a prognostic indicator for adjuvant therapy in patients who underwent
pancreatic resections for cancer.
AB - PURPOSE: In pancreatic cancer, the greatest increase in survival is attained by
surgical resection followed by adjuvant chemotherapy. Although surgical
complications and functional status are recognized as independent factors for
halting adjuvant therapy in patients that undergo pancreatic resections, other
elements may play a role in deciding which patients get treated postoperatively.
Here we determined demographic and clinical characteristics of patients receiving
adjuvant chemotherapy, with the primary intent to investigate if age alone
affects rates of adjuvant therapy. METHODS/MATERIALS: National Cancer Database
(NCDB) was queried for patients that underwent surgery for pancreatic cancer.
Groups were divided into: adjuvant chemotherapy (n=17,924) and no adjuvant
chemotherapy (n=12,947). Basic demographics and treatment characteristics were
analyzed. Age was compared with an independent means test; other comparisons used
Chi-square test of independence. RESULTS: There was a statistical difference in
age (adjuvant therapy 64.86+/-9.89 vs. no therapy 67.78+/-11.22, p<0.001),
insurance type, facility type, and cancer stage for patients that received
adjuvant therapy and those that did not. Average age of patients not receiving
chemotherapy was significantly older at each pathologic stage. Subset analysis of
patients treated with chemotherapy showed that the majority of patients received
single agent regimens (62%), at an average of 59days following surgery, and at
academic cancer programs (52%). CONCLUSIONS: Regardless of postoperative
complications and functional status, age alone appears to affect rates of
adjuvant therapy in patients with resected pancreatic cancer. Older patients
should be offered tailored regimens that would allow them to complete the
intended extent of treatment.
PMID- 29330040
TI - YOD1 attenuates neurogenic proteotoxicity through its deubiquitinating activity.
AB - Ubiquitination, a fundamental post-translational modification of intracellular
proteins, is enzymatically reversed by deubiquitinase enzymes (deubiquitinases).
>90 deubiquitinases have been identified. One of these enzymes, YOD1, possesses
deubiquitinase activity and is similar to ovarian tumor domain-containing protein
1, which is associated with regulation of the endoplasmic reticulum (ER)
associated degradation pathway. Indeed, YOD1 is reported to be involved in the ER
stress response induced by mislocalization of unfolded proteins in mammalian
cells. However, it has remained unclear whether YOD1 is associated with
pathophysiological conditions such as mitochondrial damage, impaired
proteostasis, and neurodegeneration. We demonstrated that YOD1 possesses
deubiquitinating activity and exhibits preference for K48- and K63-linked
ubiquitin. Furthermore, YOD1 expression levels increased as a result of various
stress conditions. We demonstrated that the neurogenic proteins that cause
Huntington disease and Parkinson's disease induced upregulation of YOD1 level. We
observed that YOD1 reduced disease cytotoxicity through efficient degradation of
mutant proteins, whereas this activity was abolished by catalytically inactive
YOD1. Additionally, YOD1 localized to Lewy bodies in Parkinson's disease
patients. Collectively, these data suggest that the deubiquitinase YOD1
contributes to pathogenesis of neurodegenerative disease by decreasing
ubiquitination of abnormal proteins and their subsequent degradation.
PMID- 29330041
TI - Acute epileptiform activity induced by gabazine involves proteasomal rather than
lysosomal degradation of KCa2.2 channels.
AB - Voltage-independent, Ca2+-activated K+ channels (KCa2.2, previously named SK2)
are typically activated during a train of action potentials, and hence, are
powerful regulators of cellular excitability by generating an
afterhyperpolarizing potential (AHP) following prolonged excitation. In the acute
in vitro epilepsy model induced in hippocampal brain slice preparations by
exposure to the GABAA receptor blocker gabazine (GZ), the AHP was previously
shown to be significantly decreased. Here, we asked the question whether KCa2.2
protein degradation occurs in this model and which pathways are involved. To this
end, we applied either gabazine alone or gabazine together with inhibitors of
proteasomal and lysosomal protein degradation pathways, Z-Leu-Leu-Leu-CHO (MG132)
and chloroquine (CQ), respectively. Western blot analysis showed a significant
decrease of total KCa2.2 protein content in GZ-treated slices which could be
rescued by concomitant incubation with MG132 and CQ. Using HEK293 cells
transfected with a green fluorescent protein-tagged KCa2.2 construct, we
demonstrated that proteasomal rather than lysosomal degradation was involved in
KCa2.2 reduction. We then recorded epileptiform afterdischarges at hippocampal
Schaffer collateral-CA1 synapses and confirmed that the GZ-induced increase was
significantly attenuated by both MG132 and CQ, with MG132 being significantly
more effective than CQ. Epileptiform afterdischarges were almost prevented by co
application of protein degradation inhibitors. Furthermore, epileptiform
afterdischarges could be re-established by using the KCa2.2 blocker UCL 1684
suggesting involvement of KCa2.2. We conclude that in GZ-induced acute epilepsy,
KCa2.2 degradation by proteasomal rather than lysosomal pathways plays a major
role in the generation of epileptiform afterdischarges.
PMID- 29330043
TI - HALT - A pause for anticoagulation consideration after bioprosthetic valves.
PMID- 29330042
TI - Differences in the CT findings between vulnerable plaque and culprit lesions in
acute coronary syndrome.
AB - BACKGROUND: The CT finding of "vulnerable plaque" is widely regarded as similar
to that of a culprit lesion in an acute coronary syndrome (ACS). However, this
hypothesis may not be accurate, since "vulnerable plaques" may substantially
change their morphology when they rupture to cause an ACS. METHODS: We
retrospectively evaluated coronary CT angiography data sets of 25 patients with
ACS who had vulnerable (n = 10) or culprit plaques (n = 15). We analyzed CT
features including positive remodeling (PR), low attenuation plaque (LAP), the
napkin ring sign (NRS), degree of stenosis (normal, <50%, 50-99%, 100%), and
myocardial hypoperfusion in the left ventricle. RESULTS: There was no difference
in the prevalence of PR, NRS, or LAP between vulnerable and culprit plaques. In
contrast, a majority (80%, 8/10) of vulnerable plaques were associated with <50%
luminal stenosis while total occlusion was identified in 47% (7/15) of culprit
plaques (p = .037). In all patients with occlusion, myocardial hypoperfusion was
demonstrated in the corresponding arterial territory on CT. CONCLUSION: CT
features of vulnerable and culprit plaques differ in cases with thrombotic
occlusion reflecting dynamic plaque changes related to the episode of ACS.
PMID- 29330044
TI - Effects of acupuncture on the heart rate variability, cortisol levels and
behavioural response induced by thunder sound in beagles.
AB - Sound stimuli such as fireworks, firearms, and claps of thunder have been used as
a stress reactivity model for dogs. Acupuncture has been widely used to treat and
prevent physiological and behavioural disorders induced by stress. Our study aims
to evaluate the effects of acupuncture on cardiac autonomic modulation (heart
rate variability - HRV), behavioural (reactivity) and endocrine (cortisol levels)
responses in dogs exposed to sounds of thunder. Twenty-four laboratory beagles
(12 males and 12 females, 1-6years old) with no history of phobia to thunder were
subjected to a sound stimulus that consisted of a standardized recording of
thunder over a 150s period with a maximum intensity of 103-104dB. Before the
sound, the dogs underwent a 20-minute session of needle insertion at acupuncture
points Yintang, GV20, HT7, PC6 and ST36 (ACUP), in non-points (NP) or left
undisturbed (CTL). Cardiac intervals were recorded using a frequency meter (RS
800cx, Polar, Kempele, Finland) to evaluate the HRV, and the data were later
analysed using CardioSeries v2.4.1 software. Acupuncture (ACUP) changed the
sympathovagal balance with a shift towards parasympathetic modulation, reducing
the prompt sound-induced increase in LF/HF (low frequency/high frequency) ratio
and in the power of the LF band of the cardiac interval spectrum, and decreased
the power of the HF band of the cardiac interval spectrum (p<0.05); however there
was no change in the heart rate. Acupuncture reduced the behavioural response
induced by sounds of thunder (when all behavioural parameters were considered
together) and the behaviours hiding, restlessness, bolting and running around
(when the parameters were analysed separately (p<0.05). There were no changes in
cortisol levels due to the sound stimulus or acupuncture. Our results demonstrate
that a session of acupuncture prior to sound stimulus can reduce cardiac
autonomic and behavioural responses, without changing cortisol levels in beagles.
PMID- 29330045
TI - Management of graves myopathy: Thyroid-associated orbitopathy: when should we
operate?
AB - Thyroid-associated orbitopathy (TAO) is an autoimmune disorder that affects
multiple periocular tissues. In TAO, an active immunologic inflammatory phase is
typically followed by a cicatrizing recovery phase. Management in the
inflammatory phase is supportive, and surgical rehabilitation should generally be
deferred until the patient is stable. We review current treatment concepts, with
a focus on the timing and sequence of surgical procedures to address proptosis,
motility restriction, and eyelid malposition in patients with TAO. A stepwise
surgical approach maximizes the predictability of surgical outcomes and minimizes
reoperations.
PMID- 29330046
TI - Dermoid cysts: clinical predictors of complex lesions and surgical complications.
PMID- 29330047
TI - An intrinsically disordered domain in Polaribacter irgensii KOPRI 22228 CspB
confers extraordinary freeze-tolerance.
AB - Organisms living in extremely cold environments possess mechanisms to survive low
temperatures. Among the known cold-induced genes, cold-shock proteins (Csps) are
the most prominent. A csp-homologous gene, cspBPi, has been cloned from the
Arctic bacterium Polaribacter irgensii KOPRI 22228, and overexpression of this
gene greatly increased the freezing tolerance of its host. This protein consists
of a unique N-terminal domain and a well conserved C-terminal cold shock domain.
To elucidate the detailed mechanisms involved in the extraordinary freeze
tolerance conferred by CspBPi, we identified the responsible domain by mutational
analysis. Changes of residues in the cold shock domain that are crucial for
binding RNA or single-stranded DNA did not impair the ability of the host to
survive freezing stress. All domain-shuffled CspBPi variants containing the N
terminal domain retained the ability to confer superior freeze-tolerance. Slow
electrophoretic mobility and far-UV circular dichroism spectra of the N-terminal
domain suggested an intrinsically disordered structure for this region. The N
terminal domain also bound to lipid vesicles in vitro. This lipid vesicle binding
characteristic is shared with other intrinsically disordered proteins, such as
alpha-synuclein and plant dehydrins, known to confer cold-tolerance when
overexpressed, suggesting a mechanism for cold-survival through membrane binding.
PMID- 29330048
TI - B cell activation in the cecal patches during the development of an experimental
colitis model.
AB - Although previous studies have suggested that appendix seems to be involved in
the colitis, the role of this in the pathogenesis remains unclear. In this study,
we assessed the importance of appendiceal lymphoid follicles, specifically the
cecal patches (CP) in mice, using an experimental colitis model. Treatment with
oxazolone resulted in ulcerations particularly at CP with follicular expansion as
well as colitis. The colitis was attenuated by either appendectomy or the absence
of mature B cells. We therefore established an intravital imaging system
accompanied by the fluorescence resonance energy transfer technology to analyze
the dynamic immune response of CP B cells. Our observation revealed frequent Ca2+
signaling in CP B cells during the early phase of colitis development. These
findings suggested that the CP B cells may be involved in the pathogenesis of
colitis including inflammatory bowel diseases in humans.
PMID- 29330049
TI - The histone demethylase PHF8 promotes adult acute lymphoblastic leukemia through
interaction with the MEK/ERK signaling pathway.
AB - Adult acute lymphoblastic leukemia (ALL) is a malignant disorder of lymphoid
progenitor cells that is associated with a high risk of relapse and poor
prognosis. Thus, novel pathogenic mechanisms and therapeutic targets need to be
explored. Histone methylation is one of the most significant chromatin post
translational modifications. Here, we show that the histone demethylase PHF8 is
highly expressed in a large number of ALL clinical specimens and that PHF8
expression is associated with ALL progression. PHF8 knockdown inhibits
proliferation and promotes the apoptosis of ALL cells in vitro as well as
attenuates tumor growth in vivo. PHF8 transcriptionally upregulates MEK1, a key
molecule in the MEK/ERK pathway, at least partially by directly binding to its
promoter, thereby activating the MEK/ERK pathway. In addition, we found that an
inhibitor of the MEK/ERK pathway, PD184352, subsequently suppresses PHF8
expression. Thus, PHF8 forms a positive feedback loop with the MEK/ERK pathway,
and PHF8 knockdown enhances the lethality of PD184352 in ALL cells. In
conclusion, this study identifies oncogenic functions of PHF8 in adult ALL and
suggests a novel epigenetic strategy for disease intervention.
PMID- 29330050
TI - Production and characterization of a novel site-specific-modifiable anti-OX40
receptor single-chain variable fragment for targeted drug delivery.
AB - OX40 receptor (tumor necrosis factor receptor superfamily, member 4; CD134) is a
T-cell co-stimulatory molecule that plays an important role in T-cell activation
and survival. OX40 receptor is activated by its ligand, OX40L; and modulation of
the OX40-OX40L interaction is a promising target for the treatment of autoimmune
diseases and cancers. Here, we generated a high-affinity anti-OX40 single-chain
variable fragment carrying a C-terminal cysteine residue (scFvC). Physicochemical
and functional analyses revealed that the scFvC bound to OX40-expressing cells
and was internalized via OX40-mediated endocytosis without inducing
phosphorylation of IkappaBalpha (nuclear factor of kappa light polypeptide gene
enhancer in B-cells inhibitor, alpha), an important complex in the classical
NFkappaB (nuclear factor kappa-light-chain-enhancer of activated B cells)
signaling pathway. In addition, mutation of the 36th cysteine residue in variable
region of light chain enabled site-specific chemical modification to carboxy
terminal cysteine and improved the thermal stability of the scFvC. These results
suggest that this novel high-affinity anti-OX40 scFvC may be useful as a
transporter for targeted delivery of small compounds, proteins, peptides,
liposomes, and nanoparticles, into OX40-expressing cells for the treatment of
autoimmune diseases and cancers.
PMID- 29330051
TI - Anti-tumor effects of triptolide on angiogenesis and cell apoptosis in
osteosarcoma cells by inducing autophagy via repressing Wnt/beta-Catenin
signaling.
AB - Osteosarcoma is a common malignant bone tumor occurring in adolescents and
children. The poor prognosis and low 5-year survival rate of osteosarcoma partly
due to high metastasis of osteosarcoma. Triptolide (TPL), an extract from
Tripterygium wilfordii, is widely used in cancer treatment. In our present study,
we aimed to study the effect of TPL in osteosarcoma treatment and explore the
associated regulation mechanism. Our study revealed that TPL inhibited
angiogenesis by suppressing the expression of hypoxia inducible factor-1alpha
(HIF-1alpha) and vascular endothelial growth factor (VEGF) in dose dependent
manner. Besides, cell apoptosis was induced by TPL obviously in dose dependent
manner. Further study demonstrated that TPL induced obvious cell autophagy with
increased concentration. The cooperation of autophagy inhibitor 3-MA abolished
the effect of TPL on anti-angiogenesis and apoptosis promoting. Moreover, we
found that Wnt/beta-Catenin signaling was inactivated by TPL and the adding of
pathway inducer Licl neutralized the effect of TPL on autophagy induction, anti
angiogenesis and apoptosis promoting. Taken together, we suggested that TPL
inhibited angiogenesis and induced cell apoptosis in osteosarcoma cells by
inducing autophagy via repressing Wnt/beta-Catenin signaling.
PMID- 29330053
TI - Clinical challenges of antimicrobial photodynamic therapy for bovine mastitis.
PMID- 29330052
TI - ESCO2 knockdown inhibits cell proliferation and induces apoptosis in human
gastric cancer cells.
AB - Establishment of cohesion 1 homolog 2 (ESCO2), an essential gene for cohesion
regulation and genomic stability, has not been studied in human gastric cancer
(GC). We found that ESCO2 knockdown in human GC cell lines dramatically inhibited
cell proliferation and induced cell apoptosis in vitro and suppressed tumor
xenograft development in vivo. Furthermore, adenosine monophosphate-activated
protein kinase (AMPK) was activated following the suppression of its downstream
targets, including mammalian target of rapamycin (mTOR) and p70 ribosomal S6
kinase 1 (p70S6K1), and this result was consistent with p53 activation.
Significantly, co-immunoprecipitation (Co-IP) analyses indicated that ESCO2 can
interact with p53 in GC cells. Taken together, our data demonstrate that ESCO2 is
essential for the development of GC and might be a potential therapeutic target
for treating GC.
PMID- 29330054
TI - Deterministic stability regimes and noise-induced quasistable behavior in a pair
of reciprocally inhibitory neurons.
AB - Reciprocal inhibition is a common motif exploited by neuronal networks; an
intuitive and tractable way to examine the behaviors produced by reciprocal
inhibition is to consider a pair of neurons that synaptically inhibit each other
and receive constant or noisy excitatory driving currents. In this work, we
examine reciprocal inhibition using two models (a voltage-based and a current
based integrate-and-fire model with instantaneous or temporally structured
input), and we use analytic and computational tools to examine the bifurcations
that occur and study the various possible monostable, bistable, and tristable
regimes that can exist; we find that, depending on system parameters (and on
choice of neuron model), there can exist up to 3 distinct monostable regimes
(denoted M0, M1, M2), 3 distinct bistable regimes (denoted B, B1, B2), and a
single tristable regime (denoted T). We also find that synaptic inhibition exerts
independent control over the two neurons - inhibition from neuron 1 to neuron 2
governs the spiking behavior of neuron 2 but has no impact on the spiking
behavior of neuron 1 (and vice versa). The excitatory driving current, however,
does not exhibit this property - the excitatory current to neuron 1 affects the
spiking behavior of both neurons 1 and 2 (as does the excitatory current to
neuron 2). Furthermore, we develop a methodology to examine the behavior of the
system when the excitatory driving currents are allowed to be noisy, and we
investigate the relationship between the behavior of the noisy system with the
stability regime of the corresponding deterministic system.
PMID- 29330055
TI - Tissue geometry may govern lung branching mode selection.
AB - Lung branching morphogenesis proceeds in three stereotyped modes (domain, planar,
and orthogonal branching). Much is known about the molecular players, including
growth factors such as fibroblast growth factor 10 but it is unknown how these
signals could actuate the different branching patterns. With the aim of
identifying mechanisms that may determine the different branching modes, we
developed a computational model of the epithelial lung bud and its surrounding
mesenchyme. We studied transport of morphogens and localization of morphogen flux
at lobe surfaces and lobe edges. We find that a single simple mechanism is
theoretically capable of directing an epithelial tubule to elongate, bend,
flatten, or bifurcate, depending solely on geometric ratios of the tissues in the
vicinity of a growing tubule tip. Furthermore, the same simple mechanism is
capable of generating orthogonal or planar branching, depending only on the same
geometric ratios.
PMID- 29330056
TI - Growth scaling for the early dynamics of HIV/AIDS epidemics in Brazil and the
influence of socio-demographic factors.
AB - The early dynamics of an infectious disease outbreak can be affected by various
factors including the transmission mode of the disease and host-specific factors.
While recent works have highlighted the presence of sub-exponential growth
patterns during the early phase of epidemics, empirical studies examining the
contribution of different factors to early epidemic growth dynamics are lacking.
Here we aim to characterize and explain the early incidence growth patterns of
local HIV/AIDS epidemics in Brazil as a function of socio-demographic factors.
For this purpose, we accessed annual AIDS incidence series and state-level socio
demographic variables from publicly available databases. To characterize the
early growth dynamics of the HIV/AIDS epidemic, we employed the generalized
growth model to estimate with quantified uncertainty the scaling of growth
parameter (p) which captures growth patterns ranging from constant incidence
(p=0) to sub-exponential (0 < p < 1) and exponential growth dynamics (p=1) at
three spatial scales: national, regional, and state levels. We evaluated the
relationship between socio-demographic variables and epidemic growth patterns
across 27 Brazilian states using mixed-effect regression analyses. We found wide
variation in the early dynamics of the AIDS epidemic in Brazil, displaying sub
exponential growth patterns with the p parameter estimated substantially below
1.0. The mean p was estimated to be 0.81 at the national level, with a range of
0.72-0.85 at the regional level, and a range of 0.28-0.96 at the state level. Our
findings support the notion that socio-demographic factors contribute to shaping
the early growth dynamics of the epidemic at the local level. Gini index and
socio-demographic index were negatively associated with the parameter p, whereas
urbanicity was positively associated with p. The results could have theoretical
significance in understanding differences in growth scaling across different
sexually transmitted disease systems, and have public health implications to
guide control.
PMID- 29330057
TI - Fixation and absorption in a fluctuating environment.
AB - A fundamental problem in the fields of population genetics, evolution, and
community ecology, is the fate of a single mutant, or invader, introduced in a
finite population of wild types. For a fixed-size community of N individuals,
with Markovian, zero-sum dynamics driven by stochastic birth-death events, the
mutant population eventually reaches either fixation or extinction. The classical
analysis, provided by Kimura and his coworkers, is focused on the neutral case,
[where the dynamics is only due to demographic stochasticity (drift)], and on
time-independent selective forces (deleterious/beneficial mutation). However,
both theoretical arguments and empirical analyses suggest that in many cases the
selective forces fluctuate in time (temporal environmental stochasticity). Here
we consider a generic model for a system with demographic noise and fluctuating
selection. Our system is characterized by the time-averaged (log)-fitness s0 and
zero-mean fitness fluctuations. These fluctuations, in turn, are parameterized by
their amplitude gamma and their correlation time delta. We provide asymptotic
(large N) formulas for the chance of fixation, the mean time to fixation and the
mean time to absorption. Our expressions interpolate correctly between the
constant selection limit gamma -> 0 and the time-averaged neutral case s0=0.
PMID- 29330058
TI - Haptoglobin and serum amyloid A as putative biomarker candidates of naturally
occurring bovine respiratory disease in dairy calves.
AB - Bovine respiratory disease (BRD) is one of the leading causes of morbidity and
mortality in dairy calves. Identification of reliable biomarkers of naturally
occurring BRD is essential for ensuring early diagnosis and treatment of calves
and monitoring treatment efficacy. This need is punctuated, especially in mild to
moderate cases that would greatly help to decrease recurrence and the overall
prevalence of BRD. The present study was conducted to investigate the changes in
serum concentrations of haptoglobin (Hpt) and serum amyloid A (SAA) and
association between oxidative stress and acute phase proteins (APPs) in BRD. Hpt
and SAA levels significantly increased (P < .01) in BRD stressed calves as
compared to healthy subjects. There was a significant decrease (P < .01) in serum
albumin (Alb) concentration of infected calves as compared to controls. The
oxidative stress markers revealed a significant (P < .01) increase in lipid
peroxidation (LPO) and a concurrent decrease in activities of superoxide
dismutase (SOD), reduced glutathione (R-GSH) and catalase (CAT) in BRD. A
significant correlation among APPs, extent of oxidative stress and clinical score
(CS) of calves was depicted. A stepwise decrease in Hpt and SAA and increase in
Alb was observed in infected calves post-treatment. These results suggest
implication of oxidative stress in enhancing APPs and monitoring of APPs as a
potential complement to clinical assessment of treatment in calves with naturally
occurring BRD. Hpt may be useful as the most sensitive biomarker in BRD. However,
the combined use of Hpt and oxidative stress biomarkers would greatly improve the
diagnostic accuracy.
PMID- 29330059
TI - Biosynthesis, characterization and antimicrobial activities of zinc oxide
nanoparticles from leaf extract of Glycosmis pentaphylla (Retz.) DC.
AB - Biosynthesized nanoparticles have an incredible application in biomedicine owing
to its simplicity, eco-friendly properties and low cost. The present study aims
to determine the green synthesized zinc oxide nanoparticles from methanolic leaf
extract of Glycosmis pentaphylla. The synthesized nanoparticles were
characterized using UV-VIS Spectroscopy, Fluorescence spectrometer, FT-IR, XRD,
SEM with EDAX and TEM. The confirmations of synthesized nanoparticles were
characterized by peak at 351 and 410 nm in the UV-VIS spectrum and
photoluminescence spectrum respectively. FT-IR studies revealed the functional
group of the nanoparticles. The XRD data showed the crystalline nature of the
nanoparticles and EDAX measurements indicated the 20.70% of highly pure zinc
oxide metal. The morphological characterization of synthesized zinc oxide
nanoparticles was analyzed by SEM and TEM and size of the particles were ranging
from 32 to 36 nm. The synthesized zinc oxide nanoparticles exhibited interesting
antimicrobial activity against pathogenic organisms. In addition, this is the
first report on leaf mediated synthesis of zinc oxide (ZnO) nanoparticles from
Glycosmis pentaphylla.
PMID- 29330060
TI - Induction of innate immune response following introduction of infectious
bronchitis virus (IBV) in the trachea and renal tissues of chickens.
AB - Infectious bronchitis (IB) is a highly contagious respiratory disease of
chickens, which is caused by the infectious bronchitis virus (IBV). The innate
immune response is crucial for antiviral infections and revealing the pathogenic
mechanisms of IBV. In this study, we presents an evaluation of interferon (I, II
and III IFNs) in renal and tracheal samples from chickens experimentally infected
previously vaccinated or not. The results suggest differential expression of
chicken interferon, among them type I IFN elaborate a major role in fighting off
virus. And vaccine confers greater induction ability of innate immunity thereby
vaccination prior infection occurs might be necessary. Above all, we found that
IFN-lambda also have an effect on IBV infection in trachea besides many other
respiratory virus. This study provides the first comprehensive analysis of host
virus interactions of IBV with chicken innate immune response mediated by
interferon in various groups.
PMID- 29330061
TI - Forsythoside A inhibited S. aureus stimulated inflammatory response in primary
bovine mammary epithelial cells.
AB - Forsythoside A (FTA), the major bioactive component extracted from Forsythiae
fructus, has multiple biological properties especially anti-inflammatory
property. Staphylococcus aureus (S. aureus), a Gram-positive organism, is one of
most common pathogens that cause bovine mastitis. This study evaluated the anti
inflammatory effect of FTA in S. aureus-stimulated primary bovine mammary
epithelial cells (bMEC). Primary bovine mammary epithelial cells were isolated
from the mammary tissue of lactating cows and identified as bMEC. The cell
viability of bMEC was analyzed by MTT. The bMEC were stimulated with S. aureus in
the presence or absence of FTA. Subsequently, the expression level of pro
inflammatory cytokines was determined by quantitative real-time polymerase chain
reaction (qRT-PCR). Nuclear factor-kappaB (NF-kappaB), inhibitor protein of NF
kappaB (IkappaBalpha), p38, extracellular signal-regulated protein kinase (ERK),
and c-JunN-terminal kinase (JNK) were measured by western blotting. The results
showed that the cell viability was not affected by the FTA. FTA markedly down
regulated the expressions of TNF-alpha, IL-1beta and IL-6 in S. aureus-stimulated
bMEC. In addition, FTA was found to suppress S. aureus-induced NF-kappaB and
MAPKs activation in a dose-dependent manner. These results indicated that FTA
exerted anti-inflammatory property in S. aureus-stimulated bMEC by interfering
the activation of NF-kappaB and MAPKs signaling pathways. Thereby, FTA may be a
potential therapeutic agent against inflammatory disease.
PMID- 29330062
TI - Fundus Densitometry Findings Suggest Optic Disc Hemorrhages in Primary Open-Angle
Glaucoma Have an Arterial Origin.
AB - PURPOSE: To analyze optic disc hemorrhages (DH) associated with primary open
angle glaucoma by quantifying their geometric profile and comparing their
densitometry with hemorrhages from retinal vein occlusions (RVO) and retinal
macroaneurysms (MA), which have venous and arterial sources of bleeding,
respectively. DESIGN: Retrospective cross-sectional study. METHODS: Setting:
Massachusetts Eye & Ear. POPULATION: Fundus images of DH (n = 40), MA (n = 14),
and RVO (n = 25) were identified. Patient clinical backgrounds and demographics
were obtained. MAIN OUTCOME MEASURES: Grayscale pixel intensity units of
hemorrhages and adjacent arteriole and venule over the same background tissue
were measured. Densitometry differentials (arteriole or venule minus hemorrhage
[DeltaA and DeltaV, respectively]) were calculated. The ratios of length (radial)
to midpoint width for DH were calculated. Mean DeltaA and DeltaV between groups
were compared with t tests. Multiple linear regression assessed the relation of
retinal hemorrhage diagnosis to DeltaA and DeltaV and of DH shape to DeltaA and
DeltaV. RESULTS: Mean (+/- standard deviation) DeltaA and DeltaV for DH (6.9 +/-
7.1 and -4.7 +/- 8.0 pixel intensity units, respectively) and MA (5.3 +/- 5.9 and
-6.0 +/- 4.6, respectively) were comparable (P >= .43). Mean DeltaA (14.6 +/-
7.7) and DeltaV (6.4 +/- 6.3) for RVO were significantly higher compared to DH
and MA (P < .0001) and remained significant in multivariable analyses. A unit
increase in DH length-to-width ratio was associated with 1.2 (0.5) and 1.3 (0.5)
pixel intensity unit (standard error) decrease in DeltaA and DeltaV, respectively
(P <= .014). CONCLUSIONS: DH have densitometry profiles comparable to MA and
different from RVO, suggesting that DH in glaucoma have an arterial origin.
PMID- 29330063
TI - Risk of Ischemic Kidney Injury in Patients With Nonarteritic Anterior Ischemic
Optic Neuropathy: A Nationwide Population-based Study.
AB - PURPOSE: To investigate the risk of acute tubular necrosis (ATN) in patients with
nonarteritic anterior ischemic optic neuropathy (NAION). DESIGN: Population-based
cohort study. METHODS: This is a nationwide, population-based, retrospective
study using data from the Korean national health claims database from 2011
through 2015. Patients with NAION and randomly selected control subjects from the
entire population of South Korea were enrolled. A log-rank analysis was used to
evaluate a risk of ATN in the group of patients with NAION (study group) compared
to an age-, sex-, and comorbidities-matched control group. Comorbidities included
diabetes, chronic lung disease, congestive heart failure, ischemic stroke,
anemia, septic shock, and antibiotic use. A Cox proportional hazards regression
analysis with cluster effect was performed to calculate the adjusted hazard ratio
(aHR) of ATN. RESULTS: A total of 22 498 patients were included in the study
group and 31 475 in the control group. Twenty-six cases of ATN were observed in
the NAION group and 11 in the control group. The study group was more likely to
have ATN (aHR = 2.55, 95% confidence interval: 1.50-5.91, P = .029) than the
control group. Among the 26 newly developed cases of ATN, 13 (50%) occurred in
the 0-6 months before/after NAION. CONCLUSIONS: We demonstrated that subjects
with NAION are at increased risk of ATN and suggested a possible common
mechanistic link between the 2 diseases. These results provide significant
evidence that proper patient education and further systemic evaluation of the
possibility of ATN development are required in patients with NAION.
PMID- 29330065
TI - Stargazin differentially modulates ampakine gating kinetics and pharmacology.
AB - It was previously reported that Stargazin (STG) enhances the surface expression
of AMPA receptors, controls receptor gating and slows channel desensitization as
an auxiliary subunit of the receptors. Ampakines are a class of AMPA receptor
positive allosteric modulators that modify rates of transmitter binding, channel
activity and desensitization parameters. As such, they have shown efficacy in
animal models of neurodegenerative diseases, where excitatory synaptic
transmission is compromised. Given the functional similarities between STG and
ampakines, the current study sought to probe interactions between STG and
ampakine gating properties. The effects of the high impact ampakines, CX614 and
cyclothiazide (CTZ), were compared with homomeric GluR1-flip (Glur1i) and GluR2
flop (Glur2o) receptors expressed in HEK293 cells by transient transfection with
or without STG gene. STG dramatically enhanced the surface expression of AMPA
receptors and increased glutamate-induced steady-state currents during
desensitization. STG also increased ratios of 500 MUM kainate and 500 MUM
glutamate activated steady-state currents. STG reduced association rates of
ampakines and differentially affected the dissociation rates for both CX614 and
CTZ on desensitized receptors. The estimated Kd value for CX614 was lowered from
340 MUM to 70 MUM, whereas that for CTZ was lowered from 170 MUM to 6 MUM by STG.
The data suggest that Stargazin can dramatically alter the conformation of the
receptor dimer interface where CX614 and CTZ are known to bind. This work also
demonstrates the importance of considering STG interactions when developing
ampakines to treat neurodegenerative diseases in which AMPAergic signaling is
compromised.
PMID- 29330064
TI - Antiplatelet and Anticoagulant Drugs Do Not Affect Visual Outcome in Neovascular
Age-Related Macular Degeneration in the BRAMD Trial.
AB - PURPOSE: To determine if use of antiplatelet or anticoagulant (AP/AC) medication
influences visual acuity in patients with active neovascular age-related macular
degeneration (N-AMD). DESIGN: Retrospective analysis of data from a randomized
controlled trial. METHODS: Setting: Multicenter. STUDY POPULATION: Total of 330
patients with active N-AMD from the BRAMD study, a comparative trial between
bevacizumab and ranibizumab in the Netherlands. OBSERVATION PROCEDURES: Patients
underwent an extensive ophthalmic examination. Visual acuity was categorized into
functional vision (best-corrected visual acuity [BCVA] >= 0.5), visual impairment
(BCVA < 0.5), and severe visual impairment (BCVA < 0.3). Fundus photographs were
graded for presence of retinal or subretinal hemorrhages. Information on AP/AC
medication was obtained through interview. Logistic regression analysis was used
to determine associations between AP/AC medication and outcomes. Frequency of
hemorrhages in users and non-users stratified for visual acuity categories was
analyzed with ANCOVA. MAIN OUTCOME MEASURES: BCVA and presence of hemorrhages.
RESULTS: In total, 40.9% of the patients used AP/AC medication, of which 73.3%
was aspirin. AP/AC use was not associated with visual impairment (adjusted odds
ratio [OR] 0.79; 95% confidence interval [CI] 0.43-1.44) or severe visual
impairment (adjusted OR 0.75; 95% CI 0.40-1.43). Patients on AP/AC presented with
comparable frequencies of hemorrhages (27% vs 32%, P = .32, respectively).
Similar results were found when analyses were restricted to aspirin users only.
CONCLUSION: In our study, use of AP/AC medication was associated neither with
visual decline nor with the occurrence of hemorrhages in patients with active N
AMD.
PMID- 29330067
TI - Protein complexes as psychiatric and neurological drug targets.
AB - The need for improved medications for psychiatric and neurological disorders is
clear. Difficulties in finding such drugs demands that all strategic means be
utilized for their invention. The discovery of forebrain specific AMPA receptor
antagonists, which selectively block the specific combinations of principal and
auxiliary subunits present in forebrain regions but spare targets in the
cerebellum, was recently disclosed. This discovery raised the possibility that
other auxiliary protein systems could be utilized to help identify new medicines.
Discussion of the TARP-dependent AMPA receptor antagonists has been presented
elsewhere. Here we review the diversity of protein complexes of neurotransmitter
receptors in the nervous system to highlight the broad range of protein/protein
drug targets. We briefly outline the structural basis of protein complexes as
drug targets for G-protein-coupled receptors, voltage-gated ion channels, and
ligand-gated ion channels. This review highlights heterodimers, subunit-specific
receptor constructions, multiple signaling pathways, and auxiliary proteins with
an emphasis on the later. We conclude that the use of auxiliary proteins in
chemical compound screening could enhance the detection of specific, targeted
drug searches and lead to novel and improved medicines for psychiatric and
neurological disorders.
PMID- 29330068
TI - Engineering of hydroxymandelate synthases and the aromatic amino acid pathway
enables de novo biosynthesis of mandelic and 4-hydroxymandelic acid with
Saccharomyces cerevisiae.
AB - Mandelic acid (MA) and 4-hydroxymandelic acid (HMA) are valuable specialty
chemicals used as precursors for flavors as well as for cosmetic and
pharmaceutical purposes. Today they are mainly synthesized chemically. Their
synthesis through microbial fermentation would allow for environmentally
sustainable production. In this work, we engineered the yeast Saccharomyces
cerevisiae for high-level production of MA and HMA. Expressing the
hydroxymandelate synthase from Amycolatopsis orientalis in a yeast wild type
strain resulted in the production of 119mg/L HMA from glucose. As the enzyme also
accepts phenylpyruvate as a substrate aside from its native substrate 4
hydroxyphenylpyruvate, 0.7mg/L MA was also produced. Preventing binding of 4
hydroxyphenylpyruvate to the hydroxymandelate synthase by introducing a S201V
replacement in its substrate binding site nearly completely prevented HMA
production but increased MA production only 3.5-fold. To further increase HMA and
MA production, the aromatic amino acid pathway was engineered. We increased the
precursor supply by introducing modifications in the shikimic acid pathway
(ARO1?, ARO3K222L?, ARO4K220L?) and reducing flux into the Ehrlich pathway
(aro10Delta), and thereby enhanced the HMA titer to 465mg/L and the MA titer to
2.9mg/L. A further increase in HMA and MA titers was achieved by replacing the
hydroxymandelate synthase from A. orientalis with the corresponding enzyme from
Nocardia uniformis. Subsequently, we introduced additional deletions to block the
competing tryptophan branch (trp2Delta), to further decrease flux into the
Ehrlich pathway (pdc5Delta) and to avoid transamination of phenylpyruvate and 4
hydroxyphenylpyruvate (aro8Delta, aro9Delta). We achieved more than 1g/L 4
hydroxymandelate when additionally preventing formation of phenylpyruvate by
deleting PHA2. When deleting TYR1 to prevent formation of 4-hydroxyphenylpyruvate
instead, an MA titer of 236mg/L was achieved. This is a more than 200-fold
increase in MA production compared to the wild type strain expressing the
hydroxymandelate synthase from A. orientalis. Finally, we showed that S.
cerevisiae tolerates HMA and MA to concentrations as high as 3g/L and 7.5g/L,
respectively. Our results demonstrate that S. cerevisiae is a promising host for
sustainable MA and HMA production.
PMID- 29330070
TI - Neutropenia as a Complication of Tumefactive Demyelinating Disease: A Case
Report.
AB - : Tumefactive demyelination is an aggressive, localized, generally solitary area
of demyelination that often mimics a neoplasm. We present a case of a 13-year-old
female patient who presented with sudden-onset progressive hemiplegia and
hemianopsia. Magnetic resonance imaging of the brain showed tumefactive
demyelination with partial rim of enhancement. During inpatient rehabilitation,
she developed myalgias, rash, and abdominal and mouth pain with evidence for
severe neutropenia. The neutropenia was determined to be a secondary complication
of the tumefactive disease process. This scenario may be concerning in an
inpatient rehabilitation setting, as patients share common areas, increasing the
risk of acquired infection while neutropenic. LEVEL OF EVIDENCE: V.
PMID- 29330069
TI - Conformation and Trimer Association of the Transmembrane Domain of the
Parainfluenza Virus Fusion Protein in Lipid Bilayers from Solid-State NMR:
Insights into the Sequence Determinants of Trimer Structure and Fusion Activity.
AB - Enveloped viruses enter cells by using their fusion proteins to merge the virus
lipid envelope and the cell membrane. While crystal structures of the water
soluble ectodomains of many viral fusion proteins have been determined, the
structure and assembly of the C-terminal transmembrane domain (TMD) remains
poorly understood. Here we use solid-state NMR to determine the backbone
conformation and oligomeric structure of the TMD of the parainfluenza virus 5
fusion protein. 13C chemical shifts indicate that the central leucine-rich
segment of the TMD is alpha-helical in POPC/cholesterol membranes and POPE
membranes, while the Ile- and Val-rich termini shift to the beta-strand
conformation in the POPE membrane. Importantly, lipid mixing assays indicate that
the TMD is more fusogenic in the POPE membrane than in the POPC/cholesterol
membrane, indicating that the beta-strand conformation is important for fusion by
inducing membrane curvature. Incorporation of para-fluorinated Phe at three
positions of the alpha-helical core allowed us to measure interhelical distances
using 19F spin diffusion NMR. The data indicate that, at peptide:lipid molar
ratios of ~1:15, the TMD forms a trimeric helical bundle with inter-helical
distances of 8.2-8.4A for L493F and L504F and 10.5A for L500F. These data provide
high-resolution evidence of trimer formation of a viral fusion protein TMD in
phospholipid bilayers, and indicate that the parainfluenza virus 5 fusion protein
TMD harbors two functions: the central alpha-helical core is the trimerization
unit of the protein, while the two termini are responsible for inducing membrane
curvature by transitioning to a beta-sheet conformation.
PMID- 29330071
TI - OnabotulinumtoxinA for the Treatment of Poststroke Distal Lower Limb Spasticity:
A Randomized Trial.
AB - BACKGROUND: Poststroke distal lower limb spasticity impairs mobility, limiting
activities of daily living and requiring additional caregiver time. OBJECTIVE: To
evaluate the efficacy, safety, and sustained benefit of onabotulinumtoxinA in
adults with poststroke lower limb spasticity (PSLLS). DESIGN: A multicenter,
randomized, double-blind, phase 3, placebo-controlled trial (NCT01575054).
SETTING: Sixty study centers across North America, Europe, Russia, the United
Kingdom, and South Korea. PATIENTS: Adult patients (18-65 years of age) with
PSLLS (Modified Ashworth Scale [MAS] >=3) of the ankle plantar flexors and the
most recent stroke >=3 months before study enrollment. INTERVENTIONS: During the
open-label phase, patients received <=3 onabotulinumtoxinA treatments (<=400 U)
or placebo at approximately 12-week intervals. Treatments were into the ankle
plantar flexors (onabotulinumtoxinA 300 U into ankle plantar flexors; <=100 U,
optional lower limb muscles). MAIN OUTCOME MEASUREMENTS: The double-blind primary
endpoint was MAS change from baseline (average score at weeks 4 and 6). Secondary
measures included physician-assessed Clinical Global Impression of Change (CGI),
MAS change from baseline in optional muscles, Goal Attainment Scale (GAS), and
pain scale. RESULTS: Of 468 patients enrolled, 450 (96%) completed the double
blind phase and 413 (88%) completed the study. Small improvements in MAS observed
with onabotulinumtoxinA during the double-blind phase (onabotulinumtoxinA, -0.8;
placebo, -0.6, P = .01) were further enhanced with additional treatments through
week 6 of the third open-label treatment cycle
(onabotulinumtoxinA/onabotulinumtoxinA, -1.2; placebo/onabotulinumtoxinA, -1.4).
Small improvements in CGI observed during the double-blind phase
(onabotulinumtoxinA, 0.9; placebo, 0.7, P = .01) were also further enhanced
through week 6 of the third open-label treatment cycle
(onabotulinumtoxinA/onabotulinumtoxinA, 1.6; placebo/onabotulinumtoxinA, 1.6).
Physician- and patient-assessed GAS scores improved with each subsequent
treatment. No new safety signals emerged. CONCLUSIONS: OnabotulinumtoxinA
significantly improved ankle MAS, CGI, and GAS scores compared with placebo;
improvements were consistent and increased with repeated treatments of
onabotulinumtoxinA over 1 year in patients with PSLLS. LEVEL OF EVIDENCE: I.
PMID- 29330072
TI - Chronic Thigh Pain in a Young Adult Diagnosed as Synovial Sarcoma: A Case Report.
AB - : Synovial sarcoma is a slow-growing, intermediate- to high-grade neoplasm with
extensive metastatic potential. Accurate diagnosis of synovial sarcoma may pose a
challenge to providers because of its indolent growth and variable presentation.
The findings of a soft-tissue, periarticular mass with calcifications in a young
patient are highly suggestive of synovial sarcoma. Although different imaging
modalities can aid in the diagnosis of synovial sarcoma, diagnostic certainty is
typically only confirmed by biopsy and histologic analysis. We present a case
describing the diagnostic workup of synovial sarcoma with an emphasis on imaging
findings in a patient with increasing symptomatology spanning more than a decade.
LEVEL OF EVIDENCE: V.
PMID- 29330074
TI - A nonlinear continuous-time model for a semelparous species.
AB - Periodical semelparous insects such as cicadas and May beetles exhibit
synchronization in age classes such that only one age class is present at any
point of time. This leads to outbreaks of adults as they all reach maturity
around the same time. Discrete-time models of semelparous species have shown that
this type of synchronous cycling can occur as a result of greater between-class
competition relative to within-class competition. However, relatively few studies
have examined continuous-time models of semelparous species. Here we develop a
continuous-time model for a semelparous species using a technique called the
linear chain trick to convert a non-linear McKendrick partial differential
equation into a finite system of ordinary differential equations. We represent
semelparity by a birth function whose age distribution can be made arbitrarily
narrow. We show that a Hopf bifurcation may occur in this model as a result of
competition between reproducing and non-reproducing classes. This bifurcation
leads to stable cycles in which the two classes are out of phase, thus providing
a continuous-time counterpart to the synchronous cycles that occur in discrete
time models.
PMID- 29330073
TI - The Association of Clinic-Based Mobility Tasks and Measures of Community
Performance and Risk.
AB - INTRODUCTION: Gait speed is recognized as an important predictor of adverse
outcomes in older people. However, it is unknown whether other more complex
mobility tasks are better predictors of such outcomes. OBJECTIVE: To examine a
range of clinic-based mobility tests and determine which were most strongly
associated with measures of community performance and risk (CP&R). DESIGN: Cross
sectional study. SETTING: Central Control Mobility and Aging Study, Westchester
County, New York. PARTICIPANTS: Aged >=65 years (n = 424). METHODS: Clinic-based
mobility measures included gait speed measured during normal and dual-task
conditions, the Floor Maze Immediate and Delay tasks, and stair ascending and
descending. CP&R measures were self-reported by the use of standardized
questionnaires and classified into measures of performance (distance walked,
travel outside one's home [life space], activities of daily living, and
participation in cognitive leisure activities) or risk (balance confidence, fear
of falling, and past falls). Linear and logistic regression were used to examine
associations between the clinic-based mobility measures and CP&R measures
adjusting for covariates. RESULTS: The mean age of the sample was 77.8 (SD 6.4)
years, and 55.2% (n = 234) were female. In final models, faster normal walking
speed was most strongly associated with 5 of the 7 community measures (greater
distance walked, greater life space, better activities of daily living function,
higher balance confidence, and less fear of falling; all P < .05). More complex
tasks (walking while talking and maze immediate) were associated with cognitive
leisure activity (P < .05), and ascending stairs was the only measure associated
with a history of falls (P < .05). CONCLUSION: Normal walking speed is a simple
and inexpensive clinic-based mobility test that is associated with a wide range
of CP&R measures. In addition, poorer performance ascending stairs may assist in
identifying those at risk of falls. Poorer performance in more complex mobility
tasks (walking while talking and maze immediate) may suggest inability to
participate in cognitive leisure activities. LEVEL OF EVIDENCE: III.
PMID- 29330066
TI - Regulation of vascular tone homeostasis by NO and H2S: Implications in
hypertension.
AB - Nitric oxide (NO) and hydrogen sulfide (H2S) are two gasotransmitters that are
produced in the vasculature and contribute to the regulation of vascular tone. NO
and H2S are synthesized in both vascular smooth muscle and endothelial cells; NO
functions primarily through the sGC/cGMP pathway, and H2S mainly through
activation of the ATP-dependent potassium channels; both leading to relaxation of
vascular smooth muscle cells. A deficit in the NO/H2S homeostasis is involved in
the pathogenesis of various cardiovascular diseases, especially hypertension. It
is now becoming increasingly clear that there are important interactions between
NO and H2S and that have a profound impact on vascular tone and this may provide
insights into the new therapeutic interventions. The aim of this review is to
provide a better understanding of individual and interactive roles of NO and H2S
in vascular biology. Overall, available data indicate that both NO and H2S
contribute to vascular (patho)physiology and in regulating blood pressure. In
addition, boosting NO and H2S using various dietary sources or donors could be a
hopeful therapeutic strategy in the management of hypertension.
PMID- 29330075
TI - The epidemic model based on the approximation for third-order motifs on networks.
AB - The spread of an infectious disease may depend on the structure of the network.
To study the influence of the structure parameters of the network on the spread
of the epidemic, we need to put these parameters into the epidemic model. The
method of moment closure introduces structure parameters into the epidemic model.
In this paper, we present a new moment closure epidemic model based on the
approximation of third-order motifs in networks. The order of a motif defined in
this paper is determined by the number of the edges in the motif, rather than by
the number of nodes in the motif as defined in the literature. We provide a
general approach to deriving a set of ordinary differential equations that
describes, to a high degree of accuracy, the spread of an infectious disease.
Using this method, we establish a susceptible-infected-recovered (SIR) model. We
then calculate the basic reproduction number of the SIR model, and find that it
decreases as the clustering coefficient increases. Finally, we perform some
simulations using the proposed model to study the influence of the clustering
coefficient on the final epidemic size, the maximum number of infected, and the
peak time of the disease. The numerical simulations based on the SIR model in
this paper fit the stochastic simulations based on the Monte Carlo method well at
different levels of clustering. Our results show that the clustering coefficient
poses impediments to the spread of disease under an SIR model.
PMID- 29330076
TI - Frontoethmoidal Schwannoma with Exertional Cerebrospinal Fluid Rhinorrhea: Case
Report and Review of Literature.
AB - BACKGROUND: Frontoethmoidal schwannomas are rare. No case manifesting exertional
cerebrospinal fluid (CSF) rhinorrhea has ever been reported to the best of our
knowledge. CASE DESCRIPTION: In this report, we describe an extremely rare case
of frontoethmoidal schwannoma extending through the olfactory groove with
exertional CSF rhinorrhea as the initial symptom. A 50-year-old woman was
presented to our clinic for frequent nasal discharge on exertion. A postcontrast
computed tomographic scan demonstrated heterogeneously enhanced tumor from the
anterior cranial fossa to the anterior ethmoid sinus. A gadolinium-enhanced T1
weighted magnetic resonance image revealed a well-defined heterogeneously
enhanced tumor situated in the midline anterior cranial fossa and anterior
ethmoid sinus. After the resection, the defect of the right anterior skull base
was reconstructed with a fascia graft and adipose tissue taken from the abdomen,
as well as a pedicle periosteum flap. A histologic examination revealed the tumor
as schwannoma. Her rhinorrhea completely resolved. She regained her sense of
smell and taste 1 month after the operation. CONCLUSION: According to previous
reports, olfactory groove, and paraolfactory groove/periolfactory groove
schwannomas can be divided into 4 types: subfrontal, nasoethmoidal,
frontoethmoidal, and ethmofrontal. Among them, a frontoethmoidal schwannoma can
manifest exertional CSF rhinorrhea as an initial symptom.
PMID- 29330078
TI - Intraoperative Flow Cytometry Enables the Differentiation of Primary Central
Nervous System Lymphoma from Glioblastoma.
AB - OBJECTIVE: Accurate preoperative and intraoperative differentiation between
primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) is
sometimes difficult. Distinguishing between these tumors during surgery is
important because surgical treatment is different between the 2 tumors. In this
study, we established a new method of intraoperative differentiation between
PCNSL and GBM using intraoperative flow cytometry (iFC), and we retrospectively
tested whether iFC was useful for the intraoperative diagnosis of PCNSL and GBM.
METHODS: We analyzed the iFC data of 250 patients (28 with PCNSL and 222 with
GBM) and then evaluated aneuploidy and S-phase population. RESULTS: Aneuploidy
was detected in 54.5% of GBM cases but in only 7.14% of PCNSL cases. Aneuploidy
indicated GBM, but it was difficult to distinguish PCNSL from GBM when a tumor
had a diploid pattern. Thus, for tumors without aneuploidy, we evaluated the S
phase population: S2, the ratio of the average height of the S-phase to the
height of the diploid peak. S2 was significantly higher in PCNSL than in GBM.
Based on these results, we established an algorithm for differentiating between
PCNSL and GBM using DNA aneuploidy and S2. Comparing this new iFC algorithm and
the permanent pathologic diagnosis, the sensitivity was 89.3%, the specificity
was 93.7%, and the accuracy was 93.2%. CONCLUSIONS: iFC is useful for the
intraoperative differentiation between PCNSL and GBM and it aids in
intraoperative decision making within a short time. The accuracy of
intraoperative diagnosis of these tumors seems to be higher with the combination
of iFC and intraoperative rapid pathologic diagnosis.
PMID- 29330077
TI - Blood Ethanol Levels Are Not Related to Coagulation Changes, as Measured by
Thromboelastography, in Traumatic Brain Injury Patients.
AB - BACKGROUND: Brain injury is a leading cause of death and disability in trauma
patients. Ethanol (EtOH) use near the time of injury may contribute to worse
outcomes in these patients by exacerbating coagulopathy. There are limited data
regarding the effects of EtOH on coagulation and progression of traumatic
intracranial hemorrhage (TICH). METHODS: We performed a retrospective analysis of
a prospective observational study of 168 trauma patients with TBI at an urban
level 1 trauma center. Thromboelastography (TEG) was performed on admission and
over the subsequent 48 hours. Demographic, physiologic, and outcomes data were
collected. Computed tomography imaging of the head performed within the first 48
hours of admission was analyzed for progression of TICH. RESULTS: Thirty-six
percent of patients (n = 61) had positive blood EtOH on admission (median EtOH
level = 198 mg/dL [range, 16-376 mg/dL]). EtOH-positive patients were less
severely injured than EtOH-negative patients (P = 0.01). Other admission
demographic and physiologic variables were similar between groups. There were no
significant differences in TEG values between EtOH-positive and EtOH-negative
patients on admission or during the subsequent 48 hours. There were no
differences in radiographic progression of hemorrhage, the need for neurosurgical
procedure, or mortality between EtOH-positive and EtOH-negative patients.
CONCLUSIONS: EtOH use near the time of traumatic injury was not associated with
alterations in coagulation, as measured by traditional coagulation tests or by
TEG, in patients with TICH. Furthermore, a positive blood alcohol at admission
was not associated with increased mortality or need for neurosurgical procedure
these patients.
PMID- 29330079
TI - Impact of Platelet Transfusion on Intracerebral Hemorrhage in Patients on
Antiplatelet Therapy-An Analysis Based on Intracerebral Hemorrhage Score.
AB - OBJECTIVE: Platelet transfusions for patients with intracerebral hemorrhage (ICH)
on antiplatelet therapy (APT) remain controversial. Diverging past research and
differences in platelet preparation warrant further investigation of this topic.
In this study, the association between platelet transfusion and clinical outcomes
of ICH is investigated in patients matched by ICH score, a validated predictor of
mortality. METHODS: A consecutive review of all patients from 2012 to 2015 with
nontraumatic ICH was performed. Risk factors including demographics, medical
comorbidities, APT use, and ICH score were reviewed. Standardized differences
were used to assess baseline characteristics; logistic regression models were
performed to determine whether platelet transfusions were associated with adverse
outcomes, both before and after matching for ICH score. RESULTS: A total of 538
patients with nontraumatic ICH were investigated. Of these, 168 were on APT; 71
were excluded. Thirty-nine patients (40%) received platelet transfusions and 58
(60%) did not. An overall mortality of 9.3% was measured, with 29.9% of patients
enduring complications. In the unmatched cohort, patients who received platelet
transfusions were more likely to deteriorate (odds ratio [OR], 4.7), undergo
surgical intervention during their hospital stay (OR, 7.2), be discharged with a
worse modified Rankin Scale score (OR, 3.6), or die (OR, 6.1). After matching by
ICH score, platelet transfusion was not a significant predictor for any negative
outcome. CONCLUSIONS: This is the first analysis of platelet transfusions in
patients with ICH based on ICH score. For patients on APT, platelet transfusion
is not associated with clinical outcomes in an ICH score-matched sample.
PMID- 29330080
TI - Use of Pulsed Radiofrequency Energy Device (PEAK Plasmablade) in Neuromodulation
Implant Revisions.
AB - BACKGROUND: Battery replacement or revision surgery for neuromodulation implants
is conventionally performed using sharp dissection. Meticulous dissection within
thick scar tissue is vital to avoid damage to surrounding lead(s), which could
result in more extensive revision surgery. Traditional electrosurgery devices are
contraindicated as the emitted energy can be transferred to the hardware,
resulting in implant or tissue damage with severe consequent complications.
OBJECTIVE: We report our experience and potential applications of a novel, pulsed
monopolar radiofrequency energy device (PEAK PlasmaBlade, Medtronic PLC,
Minneapolis, Minnesota, USA), which facilitates dissection around implants
without the risk of damaging or transmitting energy through the system. METHODS:
We conducted a 2-center retrospective study to review the indications, safety,
and efficacy of the PlasmaBlade in 57 cases requiring either neuromodulation
system replacement or revision. Deep brain stimulator (DBS) battery replacements
were undertaken in 45 cases, 8 vagal nerve stimulator battery revisions, 2
intrathecal baclofen system revision, 1 DBS extension revision, and 1 DBS scar
revision around the cranial portion of the lead. RESULTS: All cases proceeded
without adverse event or damage to lead/generator and with a subjective and
objective impression of significant time savings. Average operating times for
battery replacements were reduced from 37 to 26 minutes (P = 0.015). CONCLUSION:
In our experience, the PlasmaBlade is safe to use in revising/replacing
neuromodulation implants. We observed no damage or transmission of energy to the
implants or leads; additional advantages of the system include reduced operating
times, less damage to surrounding tissue, and the potential to facilitate
revision procedures in awake patients under local anesthesia.
PMID- 29330082
TI - Clinical trials recruitment planning: A proposed framework from the Clinical
Trials Transformation Initiative.
AB - Patient recruitment is widely recognized as a key determinant of success for
clinical trials. Yet a substantial number of trials fail to reach recruitment
goals-a situation that has important scientific, financial, ethical, and policy
implications. Further, there are important effects on stakeholders who directly
contribute to the trial including investigators, sponsors, and study
participants. Despite efforts over multiple decades to identify and address
barriers, recruitment challenges persist. To advance a more comprehensive
approach to trial recruitment, the Clinical Trials Transformation Initiative
(CTTI) convened a project team to examine the challenges and to issue actionable,
evidence-based recommendations for improving recruitment planning that extend
beyond common study-specific strategies. We describe our multi-stakeholder effort
to develop a framework that delineates three areas essential to strategic
recruitment planning efforts: (1) trial design and protocol development, (2)
trial feasibility and site selection, and (3) communication. Our recommendations
propose an upstream approach to recruitment planning that has the potential to
produce greater impact and reduce downstream barriers. Additionally, we offer
tools to help facilitate adoption of the recommendations. We hope that our
framework and recommendations will serve as a guide for initial efforts in
clinical trial recruitment planning irrespective of disease or intervention
focus, provide a common basis for discussions in this area and generate targets
for further analysis and continual improvement.
PMID- 29330081
TI - Optimization of a technology-supported physical activity intervention for breast
cancer survivors: Fit2Thrive study protocol.
AB - Fit2Thrive is a theory-guided physical activity promotion trial using the
Multiphase Optimization Strategy (MOST) to test efficacy for improving physical
activity of five technology-supported physical activity promotion intervention
components among breast cancer survivors. This trial will recruit 256 inactive
breast cancer survivors nationwide. All participants will receive the core
intervention which includes a Fitbit and standard self-monitoring Fit2Thrive
smartphone application which will be downloaded to their personal phone. Women
will be randomized to one of 32 conditions in a factorial design involving five
factors with two levels: support calls (No vs. Yes), app type (standard vs.
deluxe), text messaging (No vs. Yes), online gym (No vs. Yes) and Fitbit Buddy
(No vs. Yes). The proposed trial examines the effects of the components on
physical activity at 12 and 24weeks. Results will support the selection of a
final package of intervention components that has been optimized to maximize
physical activity and is subject to an upper limit of cost. The optimized
intervention will be tested in a future trial. Fit2Thrive is the first trial to
use the MOST framework to develop and test a physical activity promotion
intervention in breast cancer survivors and will lead to an improved
understanding of how to effectively change survivors' physical activity. These
findings could result in more scalable, effective physical activity interventions
for breast cancer survivors, and, ultimately, improve health and disease
outcomes.
PMID- 29330083
TI - Rationale and design of the Clinic and Community Approaches to Healthy Weight
Randomized Trial.
AB - BACKGROUND: Recent studies have demonstrated the effectiveness of family
centered, pediatric weight management programs in reducing childhood obesity.
Yet, programs to optimize the care of low-income children with obesity are
needed. We sought to examine the comparative effectiveness of two, potentially
scalable pediatric weight management programs delivered to low-income children in
a clinical or community setting. MATERIALS AND METHODS: The Clinic and Community
Approaches to Healthy Weight Trial is a randomized trial in two communities in
Massachusetts that serve a large population of low-income children and families.
The two-arm trial compares the effects of a pediatric weight management program
delivered in the Healthy Weight Clinics of two federally qualified health centers
(FQHC) to the Healthy Weight and Your Child programs delivered in two YMCAs.
Eligible children are 6 to 12 years old with a body mass index (BMI) >= 85th
percentile seen in primary care at the two FQHCs. Both programs are one-year in
duration and have at least 30 contact hours throughout the year. Measures are
collected at baseline, 6 months, and 1 year. The main outcome is 1-year change in
BMI (kg/m2) and percent change of the 95th percentile (%BMIp95). CONCLUSION: The
Clinic and Community Approaches to Healthy Weight Trial seeks to 1) examine the
comparative effects of a clinical and community based intervention in improving
childhood obesity, and 2) inform the care of >7 million children with obesity
covered by the Children's Health Insurance Program or Medicaid.
PMID- 29330084
TI - Real-time reverse transcription recombinase polymerase amplification assay for
rapid detection of porcine epidemic diarrhea virus.
AB - Porcine epidemic diarrhea (PED), which is caused by porcine epidemic diarrhea
virus (PEDV), is an acute, highly contagious enteric disease characterized by
severe watery diarrhea, vomiting, dehydration, and high mortality in suckling
piglets. A real-time reverse-transcription recombinase polymerase amplification
assay (RT-RPA) was developed based on the nucleocapsid gene of PEDV. RT-RPA assay
was performed at 40 degrees C for 20 min. The assay could detect both the
classical and variant PEDV strains, and there was no cross-reaction with other
pathogens tested. Using the in vitro transcribed PEDV RNA as template, the
analytical sensitivity was 23 copies per reaction. The assay performance was
evaluated by testing 76 clinical samples. PEDV RNA positive rate was 55.3%
(42/76) by RT-RPA and 59.2% (45/76) by real-time RT-PCR. The diagnostic agreement
between the two assays was 96.1% (73/76), and the R2 value of the two assays was
0.903 by linear regression analysis. The developed RT-RPA assay provides a useful
alternative tool for simple, rapid and reliable detection of PEDV in resource
limited diagnostic laboratories and on-site facilities.
PMID- 29330086
TI - Learning profitable habitat types by juvenile crayfish.
AB - Habitat selection is fundamentally important to animal ecology, and animals that
can learn about habitats can increase the probability of avoiding detection by
predators or quickly finding food. Here, we tested whether juveniles of the red
swamp crayfish, Procambarus clarkii, can learn preference for habitat types based
on experience with food availability. Crayfish were housed in arenas with two
habitat types, half leaf habitat and half rock habitat. Over several days,
crayfish were fed consistently in one of the habitat types. Initial tests
revealed that crayfish had an innate preference for the leaf habitat, but
conditioning over 2-3 weeks was sufficient to shift this preference to the rock
habitat based on habitat cues rather than other spatial cues in their
environment. The ability to learn the relevance of habitat features may be an
important trait for the colonization success, and subsequent impact, of
introduced species.
PMID- 29330087
TI - Comparing the antipredator behaviour of two sympatric, but not syntopic,
Liolaemus lizards.
AB - The microhabitat preferences of prey animals can modulate how they perceive
predation risk, and therefore, their antipredator behaviour. We tested under
standardized conditions how microhabitat preferences of two Liolaemus lizards
affected their responses when confronted with two types of ambush predators
(raptor vs. snake), under two levels of predation risk (low vs. high). These
lizard species are sympatric, but not syntopic; L. chiliensis basks on bushes, a
complex microhabitat that may provide protection against visual predators, while
L. nitidus prefers open microhabitats, basking on the top of large bare rocks,
highly exposed to visual predators. If microhabitat complexity modulates the
antipredator response, L. chiliensis may perceive lower predation risk,
exhibiting lower intensity of antipredator responses than L. nitidus. Both
species reduced their activity after being exposed to both predators, but lizards
differed in the assessment of predation risk; L. nitidus reduced its activity
independently of the predation risk experienced, while L. chiliensis only reduced
its activity in the high-risk condition. The microhabitat preferences shaped
during the evolution of these species seem to modulate their perception of
predation risk, which may cause interspecific differences in the associated costs
of their antipredator responses.
PMID- 29330088
TI - The flight of the locus of selection: Some intricate relationships between
evolutionary elements.
AB - Selection has enriched our understanding of the world since it was first applied
to the evolution of species. Selection stands as an alternative to essentialist
thinking, as a generalized and multiply applicable concept, and as a causal
explanation for current forms within biology and behavior. Attempts to describe
selection processes in a generalizable way have provided clarity about their
minimal elements, such as replicators and interactors. This paper discusses the
interconnectedness among different levels of selection using evidence garnered
from evolutionary biology, development, epigenetics, neuroscience, and behavior
analysis. Currently, it appears that replicators and interactors may be more
fluid than previously supposed and that selection for particular traits may rely
on both multiple levels of interaction and multiple levels of replication.
Replicators, interactors, and environment share influence on one another, and
different replicators may exchange critical control over similar interactor
variation as evolution proceeds. Our current understanding of selection continues
to undergo revision, and reference to a number of disparate fields can help to
account for the complexity of these processes. An understanding of their
interconnectedness may help resolve some mysteries that develop in fields that
exclusively focus on one or a few, such as the focused study of behavior.
PMID- 29330089
TI - Grouping promotes risk-taking in unfamiliar settings.
AB - Acting collectively in a group provides risk-reducing benefits. Yet individuals
differ in how they take risks, with some being more willing than others to
approach dangerous or unfamiliar settings. Therefore, individuals may need to
adjust their behaviour when in groups, either as a result of perceiving greater
safety or to coordinate collective responses, the latter of which may rely on
within-group dynamics biased by group composition. In zebrafish we explored how
these aspects of grouping affect risk-taking behaviour by comparing solitary to
group conditions and testing the ability of group-member solitary responses to
predict collective responses. We focused on approach-latency towards a novel
object and an unusual food to test this, for shoals of five fish. There was no
indication that collective latencies are predicted by how each fish responded
when alone in terms of the extremes, the variance or the mean of group-member
latency towards the unusual food and the novel-object. However, fish were overall
faster and less variable in their approach when shoaling. This indicates lower
risk aversion by individuals in groups, presumably as a result of group safety.
An interesting consequence of the overall low risk-aversion in shoals is that
more risk-aversive fish adjust their behaviour more than less risk averse fish.
PMID- 29330085
TI - Inflammation following acute myocardial infarction: Multiple players, dynamic
roles, and novel therapeutic opportunities.
AB - Acute myocardial infarction (AMI) and the heart failure that often follows, are
major causes of death and disability worldwide. As such, new therapies are
required to limit myocardial infarct (MI) size, prevent adverse left ventricular
(LV) remodeling, and reduce the onset of heart failure following AMI. The
inflammatory response to AMI, plays a critical role in determining MI size, and a
persistent pro-inflammatory reaction can contribute to adverse post-MI LV
remodeling, making inflammation an important therapeutic target for improving
outcomes following AMI. In this article, we provide an overview of the multiple
players (and their dynamic roles) involved in the complex inflammatory response
to AMI and subsequent LV remodeling, and highlight future opportunities for
targeting inflammation as a therapeutic strategy for limiting MI size, preventing
adverse LV remodeling, and reducing heart failure in AMI patients.
PMID- 29330090
TI - Evaluation of the confusion matrix method in the validation of an automated
system for measuring feeding behaviour of cattle.
AB - The aim of the present study was to evaluate empirically confusion matrices in
device validation. We compared the confusion matrix method to linear regression
and error indices in the validation of a device measuring feeding behaviour of
dairy cattle. In addition, we studied how to extract additional information on
classification errors with confusion probabilities. The data consisted of 12 h
behaviour measurements from five dairy cows; feeding and other behaviour were
detected simultaneously with a device and from video recordings. The resulting
216 000 pairs of classifications were used to construct confusion matrices and
calculate performance measures. In addition, hourly durations of each behaviour
were calculated and the accuracy of measurements was evaluated with linear
regression and error indices. All three validation methods agreed when the
behaviour was detected very accurately or inaccurately. Otherwise, in the
intermediate cases, the confusion matrix method and error indices produced
relatively concordant results, but the linear regression method often disagreed
with them. Our study supports the use of confusion matrix analysis in validation
since it is robust to any data distribution and type of relationship, it makes a
stringent evaluation of validity, and it offers extra information on the type and
sources of errors.
PMID- 29330091
TI - CDC42EP4, a perisynaptic scaffold protein in Bergmann glia, is required for
glutamatergic tripartite synapse configuration.
AB - Configuration of tripartite synapses, comprising the pre-, post-, and peri
synaptic components (axon terminal or bouton, dendritic spine, and astroglial
terminal process), is a critical determinant of neurotransmitter kinetics and
hence synaptic transmission. However, little is known about molecular basis for
the regulation of tripartite synapse morphology. Previous studies showed that
CDC42EP4, an effector protein of a cell morphogenesis regulator CDC42, is
expressed exclusively in Bergmann glia in the cerebellar cortex, that it forms
tight complex with the septin heterooligomer, and that it interacts indirectly
with the glutamate transporter GLAST and MYH10/nonmuscle myosin IotaIotaB.
Scrutiny of Cdc42ep4-/- mice had revealed that the CDC42EP4-septins-GLAST
interaction facilitates glutamate clearance, while the role for CDC42EP4-septins
MYH10 interaction has remained unsolved. Here, we find anomalous configuration of
the tripartite synapses comprising the parallel fiber boutons, dendritic spines
of Purkinje cells, and Bergmann glial processes in Cdc42ep4-/- mice. The complex
anomalies include 1) recession of Bergmann glial membranes from the nearest
active zones, and 2) extension of nonactive synaptic contact around active zone.
In line with the recession of Bergmann glial membranes by the loss of CDC42EP4,
overexpression of CDC42EP4 in heterologous cells promotes cell spreading and
partitioning of MYH10 to insoluble (i.e., active) fraction. Paradoxically,
however, Cdc42ep4-/- cerebellum contained significantly more MYH10 and N
cadherin, which is attributed to secondary neuronal response mainly in Purkinje
cells. Given cooperative actions of N-cadherin and MYH10 for adhesion between
neurons, we speculate that their augmentation may reflect the extension of
nonactive synaptic contacts in Cdc42ep4-/- cerebellum. Transcellular mechanism
that links the absence of CDC42EP4 in Bergmann glia to the augmentation of N
cadherin and MYH10 in neurons is currently unknown, but the phenotypic similarity
to GLAST-null mice indicates involvement of the glutamate intolerance. Together,
the unique phenotype of Cdc42ep4-/- mice provides a clue to novel molecular
network underlying tripartite synapse configuration.
PMID- 29330092
TI - A novel double-antigen sandwich ELISA for the species-independent detection of
Crimean-Congo hemorrhagic fever virus-specific antibodies.
AB - Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease in humans caused
by the CCHF virus (CCHFV). The detection of anti-CCHFV antibodies in animals is
used to reveal infection risk areas. Therefore a simple, quick and reliable
multispecies assay for the detection of CCHFV-specific antibodies is needed. This
work presents the development and validation of a novel CCHF double-antigen ELISA
for the detection of anti-CCHFV nucleoprotein antibodies. The test requires 30
MUl of serum, and results are obtained within 90 min. As the ELISA is based on
recombinant N-protein of the IbAr10200 virus, it can be run under standard
biosafety conditions. For assay validation, sera from 95 cattle and 176 small
ruminants from CCHF-endemic regions (origin: Albania, Cameroon, Kosovo, Former
Yugoslav Republic of Macedonia, Mauritania, Pakistan, Turkey) served as a
positive reference serum panel. The CCHF antibody status of the positive
reference samples had been previously confirmed by two serological assays
(species-adapted VectorBest ELISA and Euroimmun IFA). CCHFV strains belonging to
three different clades are known to circulate in the countries where the positive
samples originated. Sera from 402 cattle and 804 small ruminants from Germany and
France served as the negative serum panel, as both countries are considered
outside of the CCHFV endemic zone. Sera from monkeys, camels, rats, ferrets,
raccoon dogs, raccoons, foxes, hares, pigs and humans were also tested, to
determine the suitability of this novel ELISA for these species. All negative
reference sera were confirmed by the CCHF double-antigen ELISA, indicating a
specificity of 100%. 268 of 271 positive reference sera tested positive for CCHFV
specific antibodies, 8sensitivity of 99%9. Further analysis are needed to ensure
a recognition of the IbAr10200 nucleoprotein by antibodies directed against all
known CCHFV clades. This is planned to be realized with sera from other regions
covering the three missing clades.
PMID- 29330094
TI - P21 activated kinase signaling in cancer.
AB - The p21 Activated Kinases (PAKs) are a family of serine threonine kinases, that
consist of 6 members, PAKs 1-6, which are positioned at an intersection of
multiple signaling pathways implicated in oncogenesis. The PAKs were originally
identified as protein kinases that function downstream of the Ras related Rho
GTPases Cdc42 and Rac. PAK1 and PAK4, which belong to Group I and Group II PAKs,
respectively, are most often associated with tumorigenesis. On account of their
well characterized roles in cancer, several small molecule inhibitors are being
developed to inhibit the PAKs, and there is interest in investigating their
efficacy as either first line or adjuvant treatments for cancer. Studies to
delineate PAK regulated signaling pathways as well as the long term effects of
PAK overexpression on gene expression are beginning to shed light on the
mechanism by which PAK proteins may lead to cancer when they are overexpressed or
activated. This review will describe the association between PAK expression in
cancer, with a focus on PAK1 and PAK4, which are most often associated with the
disease. The current understanding of the molecular mechanisms by which the PAKs
operate in cancer will be discussed. We will also review some of the potential
drug candidates, and discuss which of them are currently being tested for their
efficacy in cancer treatments.
PMID- 29330093
TI - Designing improved active peptides for therapeutic approaches against infectious
diseases.
AB - Infectious diseases are one of the main causes of human morbidity and mortality.
In the last few decades, pathogenic microorganisms' resistance to conventional
drugs has been increasing, and it is now pinpointed as a major worldwide health
concern. The need to search for new therapeutic options, as well as improved
treatment outcomes, has therefore increased significantly, with biologically
active peptides representing a new alternative. A substantial research effort is
being dedicated towards their development, especially due to improved
biocompatibility and target selectivity. However, the inherent limitations of
peptide drugs are restricting their application. In this review, we summarize the
current status of peptide drug development, focusing on antiviral and
antimicrobial peptide activities, highlighting the design improvements needed,
and those already being used, to overcome the drawbacks of the therapeutic
application of biologically active peptides.
PMID- 29330095
TI - Crosstalk between Rac1-mediated actin regulation and ROS production.
AB - The small RhoGTPase Rac1 is implicated in a variety of events related to actin
cytoskeleton rearrangement. Remarkably, another event that is completely
different from those related to actin regulation has the same relevance; the Rac1
mediated production of reactive oxygen species (ROS) through NADPH oxidases
(NOX). Each outcome involves different Rac1 downstream effectors; on one hand,
events related to the actin cytoskeleton require Rac1 to bind to WAVEs proteins
and PAKs that ultimately promote actin branching and turnover, on the other, NOX
derived ROS production demands active Rac1 to be bound to a cytosolic activator
of NOX. How Rac1-mediated signaling ends up promoting actin-related events, NOX
derived ROS, or both is poorly understood. Rac1 regulators, including scaffold
proteins, are known to exert tight control over its functions. Hence, evidence of
Rac1 regulatory events leading to both actin remodeling and NOX-mediated ROS
generation are discussed. Moreover, cellular functions linked to physiological
and pathological conditions that exhibit crosstalk between Rac1 outcomes are
analyzed, while plausible roles in neuronal functions (and dysfunctions) are
highlighted. Together, discussed evidence shed light on cellular mechanisms which
requires Rac1 to direct either actin- and/or ROS-related events, helping to
understand crucial roles of Rac1 dual functionality.
PMID- 29330096
TI - Selenoprotein H controls cell cycle progression and proliferation of human
colorectal cancer cells.
AB - Selenoprotein H (SELENOH) is supposed to be involved in redox regulation as well
as in tumorigenesis. However, its role in healthy and transformed cells of the
gastrointestinal tract remains elusive. We analyzed SELENOH expression in cells
depending on their selenium supply and differentiation status and found that
SELENOH expression was increased in tumor tissue, in undifferentiated epithelial
cells from mice and in colorectal cancer lines as compared to more differentiated
ones. Knockdown studies in human colorectal cancer cells revealed that repression
of SELENOH decreased cellular differentiation and increased proliferation and
migration. In addition, SELENOH knockdown cells have a higher competence to form
colonies or tumor xenografts. In parallel, they show a faster cell cycle
transition. The high levels of SELENOH in tumors as well as in undifferentiated,
proliferative cells together with its inhibitory effects on proliferation and
G1/S phase transition suggest SELENOH as a key regulator for cell cycle
progression and for prevention of uncontrolled proliferation. As SELENOH
expression is highly dependent on the selenium status, effects of selenium
supplementation on cancer initiation and progression appear to involve SELENOH.
PMID- 29330098
TI - Missed Opportunities in Colorectal Cancer Prevention in Patients With Inadequate
Bowel Preparations.
PMID- 29330099
TI - Confusion for Fifteen Years: A Case of Abernethy Malformation.
PMID- 29330097
TI - Learning situated emotions.
AB - From the perspective of constructivist theories, emotion results from learning
assemblies of relevant perceptual, cognitive, interoceptive, and motor processes
in specific situations. Across emotional experiences over time, learned
assemblies of processes accumulate in memory that later underlie emotional
experiences in similar situations. A neuroimaging experiment guided participants
to experience (and thus learn) situated forms of emotion, and then assessed
whether participants tended to experience situated forms of the emotion later.
During the initial learning phase, some participants immersed themselves in
vividly imagined fear and anger experiences involving physical harm, whereas
other participants immersed themselves in vividly imagined fear and anger
experiences involving negative social evaluation. In the subsequent testing
phase, both learning groups experienced fear and anger while their neural
activity was assessed with functional magnetic resonance imaging (fMRI). A
variety of results indicated that the physical and social learning groups
incidentally learned different situated forms of a given emotion. Consistent with
constructivist theories, these findings suggest that learning plays a central
role in emotion, with emotion adapted to the situations in which it is
experienced.
PMID- 29330100
TI - Osteoarthritis year in review 2017: updates on imaging advancements.
AB - OBJECTIVE: This narrative review covers original research publications related to
imaging advancements in osteoarthritis (OA) published in the English language
between 1st April 2016 and 30th April 2017. METHODS: Relevant human studies
(excluding pre-clinical and in vitro studies), were searched and selected from
PubMed database using the search terms of "osteoarthritis (OA)" in combination
with "radiography", "magnetic resonance imaging (MRI)", "computed tomography
(CT)", "ultrasound", "positron emission tomography (PET)," "single-photon
emission computed tomography (SPECT)," and "scintigraphy". The included studies
were sorted according to their relevance, novelty, and impact. Original research
articles with both imaging advancements and novel clinical information were
discussed in this review. RESULTS: A large portion of the published studies were
focused on MRI-based semi-quantitative and quantitative (morphological and
structural) metrics of the knee joint to assess OA-related structural damages.
New imaging technologies, such as PET, have been investigated for OA diagnosis
and characterization, the delineation of predictive factors for OA progression,
and to monitor the treatment responses. CONCLUSION: Advanced imaging modalities
play a pivotal role in OA research, and make a significant contribution to our
understanding of OA diagnosis, pathogenesis, risk stratification, and prognosis.
PMID- 29330101
TI - Telephone-based weight loss support for patients with knee osteoarthritis: a
pragmatic randomised controlled trial.
AB - OBJECTIVE: To determine the effectiveness of telephone-based weight loss support
in reducing the intensity of knee pain in patients with knee osteoarthritis, who
are overweight or obese, compared to usual care. DESIGN: We conducted a parallel
randomised controlled trial (RCT), embedded within a cohort multiple RCT of
patients on a waiting list for outpatient orthopaedic consultation at a tertiary
referral hospital in NSW, Australia. Patients with knee osteoarthritis,
classified as overweight or obese [body mass index (BMI) between >=27 kg/m2 and
<40 kg/m2] were randomly allocated to receive referral to an existing non-disease
specific government funded 6-month telephone-based weight management and healthy
lifestyle service or usual care. The primary outcome was knee pain intensity
measured using an 11-point numerical rating scale (NRS) over 6-month follow-up. A
number of secondary outcomes, including self-reported weight were measured. Data
analysis was by intention-to-treat according to a pre-published analysis plan.
RESULTS: Between May 19 and June 30 2015, 120 patients were randomly assigned to
the intervention (59 analysed, one post-randomisation exclusion) or usual care
(60 analysed). We found no statistically significant between group differences in
pain intensity [area under the curve (AUC), mean difference 5.4, 95%CI: -13.7 to
24.5, P = 0.58] or weight change at 6 months (self-reported; mean difference
0.4, 95%CI: -2.6 to 1.8, P = 0.74). CONCLUSIONS: Among patients with knee
osteoarthritis who are overweight, telephone-based weight loss support, provided
using an existing 6-month weight management and healthy lifestyle service did not
reduce knee pain intensity or weight, compared with usual care. TRIAL
REGISTRATION NUMBER: ACTRN12615000490572.
PMID- 29330102
TI - Bisphosphonates intake and its association with changes of periarticular bone
area and three-dimensional shape: data from the Osteoarthritis Initiative (OAI).
AB - OBJECTIVE: To determine the association between bisphosphonate treatment with the
change of periarticular bone area and three-dimensional (3D) shape in
participants of the Osteoarthritis Initiative (OAI) study. DESIGN: Using
propensity score (PS) matching method in females, 48 bisphosphonate users and 105
non-users, who were matched for osteoarthritis (OA) and osteoporosis (OP) related
factors were included. Baseline and 24-month magnetic resonance imaging (MRI)
based periarticular bone area and 3D shape measurements were used. The
association between bisphosphonate intake and 24-month interval changes of the
periarticular bone area and 3D shape were evaluated using paired Wilcoxon signed
rank test. We used conditional logistic regression models for determining the
association between bisphosphonate intake and periarticular bone change, defined
using the standard deviation of difference (SDD) and reliable change index (RCI)
methods. P-values have been adjusted for multiple comparisons using Benjamini &
Hochberg procedure and false discovery rate (FDR)-adjusted P-values were
reported. RESULTS: The 24-month interval increases in the periarticular bone area
in medial side of tibia were significantly greater in non-users than users (FDR
adjusted P-value: 0.002). There was an approaching significance trend for lower
medial tibial periarticular bone area expansion in bisphosphonate users in
comparison with non-users (For 1SDD change, odds ratio 95% confidence interval
(OR (95% CI)): 0.514 (0.271-0.975), FDR-adjusted P-value: 0.085) (For 1.96RCI
change, OR (95% CI): 0.552 (0.309-0.986), FDR-adjusted P-value: 0.085).
CONCLUSIONS: Bisphosphonate intake was associated with a reduction in the odds
(approaching but not achieving significance) of expansion periarticular bone
area, specifically in the medial tibial sub-region.
PMID- 29330103
TI - Osteoarthritis year in review 2017: rehabilitation and outcomes.
AB - OBJECTIVE: The purpose of this systematic review was to describe studies
examining rehabilitation for people with osteoarthritis (OA) and to summarize
findings from selected key systematic reviews (SRs) and randomized controlled
trials (RCTs). DESIGN: A systematic search was performed using Pubmed, Embase and
Cochrane databases from April 1st 2016 to May 15th 2017 using the terms
'osteoarthritis', 'randomized controlled trial', and 'systematic review'.
Inclusion criteria were: clinically or radiologically diagnosed patients with OA,
rehabilitation treatment, RCT or SRs. A selection of the included studies is
discussed based on study quality and perceived importance to the field; including
those that are innovative, inform the direction of the field or generate
controversy. Methodological quality of the included studies was assessed using
the PEDro-scale for RCTs and the Amstar guideline for SRs. RESULTS: From 1211
articles, 80 articles met the eligibility criteria including 21 SRs and 61 RCTs.
The median of the methodological quality of the SRs and RCTs was 7 (2-9) and 6 (3
10), respectively. The studies were grouped into several themes, covering the
most important rehabilitation fields. CONCLUSIONS: Striking is the small number
of studies investigating another joint (18%) than the knee (82%). Exercise is the
most common treatment evaluated and should be accompanied with education to
effectuate a behavioural change in physical activity of people with OA. No new
insights in the field of braces (or orthoses) and in the field of acupuncture
were found.
PMID- 29330104
TI - Circular RNA: An emerging non-coding RNA as a regulator and biomarker in cancer.
AB - Circular RNA (circRNA) is a type of covalently closed non-coding RNA that may
regulate gene expression in eukaryotes. The recent application of high-throughput
RNA sequencing and bioinformatics approaches has revealed a large number of
circRNAs in human cells. Emerging evidence indicates that many circRNAs have cell
type specific expression and are linked to physiological development and various
diseases. Specially, circRNAs can either serve as oncogenic stimuli or tumor
suppressors in cancer. circRNAs have also been shown to be enriched and stable in
extracellular fluid, indicating the potential of circRNAs as cancer biomarkers.
Here, we summarize the current knowledge of circRNAs, including their
classification, biogenesis, properties, and databases, as well as their function
and clinical implications in cancer.
PMID- 29330105
TI - Redox regulation of microRNAs in cancer.
AB - Dysregulation of microRNAs (miRNAs) has long been implicated in tumorigenesis,
whereas the underlying mechanisms remain largely unknown. Oxidative stress is a
hallmark of cancer that involved in multiple pathophysiological processes,
including the aberrant regulation of miRNAs. Compelling evidences have implied
complicated interplay between reactive oxygen species (ROS) and miRNAs. Indeed,
ROS induces carcinogenesis through either reducing or increasing the miRNA level,
leading to the activation of oncogenes or silence of tumor suppressors,
respectively. In turn, miRNAs target ROS productive genes or antioxidant
responsive elements to affect cellular redox balance, which contributes to
establishing a microenvironment favoring cancer cell growth and metastasis. Both
miRNAs and ROS have been identified as potential biomarkers and therapeutic
targets in human malignancies, and comprehensive understanding of the molecular
events herein will facilitate the development of novel cancer therapeutic
strategies.
PMID- 29330106
TI - Featuring the special issue Guest Editor.
PMID- 29330107
TI - Prostate cancer-associated lncRNAs.
AB - Long non-coding RNA (LncRNA) is defined as an RNA transcript that does not encode
any protein, with a length longer than 200 nt. Based on the recent advances in
high-throughput sequencing techniques, a large number of lncRNAs have been
characterized as functional transcripts that play important roles in various
biological processes as well as pathologic states. In a research field of
prostate cancer, several key lncRNAs have been identified as new players that
contribute to the pathophysiology of the disease, which is primarily regulated by
androgen and its cognate receptor. This review sheds light on the history and
future perspective of these prostate cancer-associated lncRNAs.
PMID- 29330108
TI - Membrane-lipid associated lncRNA: A new regulator in cancer signaling.
AB - Long noncoding RNAs (LncRNAs) are one of the emerging regulators which are
involved in diverse biological processes. LncRNAs can participate in the
regulation of gene expression via various ways in the cytoplasm and the nucleus.
The function of the nuclear lncRNAs has been studied a lot. Recent studies have
shown that the regulatory roles of cytoplasmic lncRNA, including membrane lipid
associated lncRNA, which may open an unexplored mechanistic territory. LncRNA
dysregulated expression represents a common event in pathogenesis of a variety of
human genetic diseases including cancer. Lipid-associated lncRNA is capable of
modulating critical cellular functions by directly interacting with phospholipids
on the plasma membrane. Besides, it also could be a predictor for the poor
prognosis of cancer. In this review, we sum up the roles of cytoplasmic lncRNA,
especially lipid-associated lncRNA in cancer.
PMID- 29330109
TI - Friend or Foe: MicroRNAs in the p53 network.
AB - The critical tumor suppressor gene TP53 is either lost or mutated in more than
half of human cancers. As an important transcriptional regulator, p53 modulates
the expression of many microRNAs. While wild-type p53 uses microRNAs to suppress
cancer development, microRNAs that are activated by gain-of-function mutant p53
confer oncogenic properties. On the other hand, the expression of p53 is tightly
controlled by a fine-tune machinery including microRNAs. MicroRNAs can target the
TP53 gene directly or other factors in the p53 network so that expression and
function of either the wild-type or the mutant forms of p53 is downregulated.
Therefore, depending on the wild-type or mutant p53 context, microRNAs contribute
substantially to suppress or exacerbate tumor development.
PMID- 29330110
TI - Epigenetics and pathogenesis of systemic sclerosis; the ins and outs.
AB - The pathogenesis of many diseases is influenced by environmental factors which
can affect human genome and be inherited from generation to generation. Adverse
environmental stimuli are recognized through the epigenetic regulatory complex,
leading to gene expression alteration, which in turn culminates in disease
outcomes. Three epigenetic regulatory mechanisms modulate the manifestation of a
gene, namely DNA methylation, histone changes, and microRNAs. Both epigenetics
and genetics have been implicated in the pathogenesis of systemic sclerosis (SSc)
disease. Genetic inheritance rate of SSc is low and the concordance rate in both
monozygotic (MZ) and dizygotic (DZ) twins is little, implying other possible
pathways in SSc pathogenesis scenario. Here, we provide an extensive overview of
the studies regarding different epigenetic events which may offer insights into
the pathology of SSc. Furthermore, epigenetic-based interventions to treat SSc
patients were discussed.
PMID- 29330111
TI - Soluble Major Histocompatibility Complex Class I related Chain A (sMICA) levels
influence graft outcome following Renal Transplantation.
AB - BACKGROUND: Since soluble isoforms of MICA play an important role in modulating
the immune response, we evaluated a possible correlation between their levels and
development of acute rejection following renal transplantation. METHODS: Serum
samples collected at pre- and different time points post-transplant from 137 live
related donor renal transplant recipients were evaluated retrospectively for
sMICA levels and for the presence of MICA antibodies. Samples from 30 healthy
volunteers were also tested as controls. RESULTS: Significantly higher levels of
sMICA were observed in the pretransplant sera of allograft recipients as compared
to healthy controls. Patients with acute cellular rejection experienced a
significant fall in their levels at the time of diagnosis as compared to their
pretransplant values and posttransplant follow up time points (p = .01, .003,
.005 and .04 respectively at pre vs biopsy (Bx), POD7 vs Bx, POD 30 vs Bx, POD 90
vs Bx). However, no such difference was noted in patients undergoing antibody
mediated rejection. Further the study did not reveal any correlation on the
presence/absence of MICA antibodies with either an increase or decrease in sMICA
levels. CONCLUSIONS: Estimating circulating levels of soluble MICA could provide
useful information of prognostic importance in assessing graft outcome following
renal transplantation.
PMID- 29330113
TI - Runt-related transcription factor 1 (RUNX1) deficiency attenuates inflammation
induced pro-inflammatory and pro-labour mediators in myometrium.
AB - Identifying new targets that regulate myometrial activation are required to
develop effective treatments to stop preterm labor. Inflammation, which can be
induced by sterile or infective insults, plays a role in initiating and
maintaining uterine contractions. Several high throughput transcription screening
studies have identified an upregulation of runt-related transcription factor 1
(RUNX1) mRNA expression in myometrium with labor. The role of RUNX1 in labor,
however, is not known. We report increased RUNX1 during late gestation which was
further augmented in labor, suggesting that RUNX1 may be involved in the
transition of the myometrium from a quiescent into a contractile state in
preparation for labor. By inhibiting the expression of RUNX1, we have established
that RUNX1 induces the expression of pro-inflammatory cytokines, chemokines,
adhesion molecules, contraction-associated proteins OXR and PTGFR, the uterotonic
PGF2alpha, and the ECM remodelling enzyme MMP9. Targeting RUNX1 may be a novel
approach to prevent preterm labor.
PMID- 29330112
TI - Macrochimerism and clinical transplant tolerance.
AB - Current theory holds that macrochimerism is essential to the development of
transplant tolerance. Hematopoietic cell transplantation from the solid organ
donor is necessary to achieve macrochimerism. Over the last 10-20 years, trials
of tolerance induction with combined kidney and hematopoietic cell
transplantation have moved from the preclinical to the clinical arena. The
achievement of macrochimerism in the clinical setting is challenging, and
potentially toxic due to the conditioning regimen necessary to hematopoietic cell
transplantation and due to the risk of graft-versus-host disease. There are
differences in chimerism goals and methods of the three major clinical stage
tolerance induction strategies in both HLA-matched and HLA-mismatched living
donor kidney transplantation, with consequent differences in efficacy and safety.
The Stanford protocol has proven efficacious in the induction of tolerance in HLA
matched kidney transplantation, allowing cessation of immunosuppressive drug
therapy in 80% of study participants, with the safety profile of conventional
transplantation. In HLA-mismatched transplantation, multi-lineage macrochimerism
of over a year's duration can now be consistently achieved with the Stanford
protocol, with complete withdrawal of immunosuppressive drug therapy during the
second post-transplant year as the next experimental step and test of tolerance.
PMID- 29330114
TI - Human CD4+ CD25+ CD127hi cells and the Th1/Th2 phenotype.
AB - CD4+ T cells that co-express CD25 and CD127 (CD25+CD127+) make up around 20% of
all circulating CD4+ memory T cells in healthy people. The clinical significance
of these cells is that in children with type 1 diabetes their relative frequency
at diagnosis is significantly and directly correlated with rate of disease
progression. The purpose of this study was to further characterize the
CD25+CD127hi cells. We show that they are a mix of Th1 and Th2 cells however,
they have a significantly higher relative frequency of pre-committed and
committed Th2 cells, and secrete significantly higher levels of Th2-type
cytokines than CD25- memory T cells. Further, these cells are neither exhausted
nor senescent and proliferate to the same extent as CD25- memory cells. Thus,
CD25+CD127hi cells are a highly active subset of memory T cells that might play a
role in controlling inflammation via anti-inflammatory Th2-type deviation.
PMID- 29330115
TI - Pediatric-onset Evans syndrome: Heterogeneous presentation and high frequency of
monogenic disorders including LRBA and CTLA4 mutations.
AB - Evans syndrome (ES) is defined by the combination of autoimmune hemolytic anemia
and immune thrombocytopenia. Clinical presentation includes manifestations of
immune dysregulation, found in primary immune deficiencies, autoimmune
lymphoproliferative syndrome with FAS (ALPS-FAS), Cytotoxic T Lymphocyte Antigen
4 (CTLA-4) and Lipopolysaccharide-Responsive vesicle trafficking Beige-like and
Anchor protein (LRBA) defects. We report the clinical history and genetic results
of 18 children with ES after excluding ALPS-FAS. Thirteen had organomegaly, five
lymphocytic infiltration of non-lymphoid organs, nine hypogammaglobulinemia and
fifteen anomalies in lymphocyte phenotyping. Seven patients had genetic defects:
three CTLA4 mutations (c.151C>T; c.109+1092_568-512del; c.110-2A>G) identified by
Sanger sequencing and four revealed by Next Generation Sequencing: LRBA
(c.2450+1C>T), STAT3 gain-of-function (c.2147C>T; c.2144C>T) and KRAS (c.37G>T).
No feature emerged to distinguish patients with or without genetic diagnosis. Our
data on pediatric-onset ES should prompt physicians to perform extensive
screening for mutations in the growing pool of genes involved in primary immune
deficiencies with autoimmunity.
PMID- 29330116
TI - TNF-alpha increases Staphylococcus aureus-induced death of human alveolar
epithelial cell line A549 associated with RIP3-mediated necroptosis.
AB - AIM: To explore the role of tumor necrosis factor-alpha (TNF-alpha) on
Staphylococcus aureus-induced necroptosis in alveolar epithelial cells. MAIN
METHODS: The A549 alveolar epithelial cell line was pretreated with small
interfering RNA (siRNA) against receptor interacting protein-3 (RIP3) and then
stimulated by S. aureus, where some cells were pretreated with TNF-alpha or TNF
alpha with anti-TNF-alpha antibody simultaneously. A549 cell death was assessed
using lactate dehydrogenase (LDH) leakage and flow cytometry analyses. The
protein expressions of RIP1, RIP3, cleaved caspase-1, and cleaved caspase-8 were
analyzed by western blot. KEY FINDINGS: S. aureus-induced LDH release was
increased significantly by TNF-alpha. In addition, flow cytometry showed that TNF
alpha increased A549 cell apoptosis and necrosis in S. aureus-infected cell
cultures. Levels of RIP3 and cleaved caspase-1 protein in A549 cells infected
with S. aureus increased at 12 h post-infection, as shown by western blot.
Significant additional increases in RIP3 expression were observed following the
addition of TNF-alpha. Decreasing RIP3 levels by siRNA significantly suppressed
the release of LDH induced by TNF-alpha and S. aureus. RIP3 siRNA also
significantly suppressed A549 cell necrosis induced by S. aureus and TNF-alpha at
6 and 12 h post-infection as shown by flow cytometry analysis. SIGNIFICANCE: TNF
alpha enhances the damage of S. aureus on lung epithelial cells, and its
mechanism is associated with RIP3 mediated necroptosis.
PMID- 29330118
TI - Using the Ribodeblur pipeline to recover A-sites from yeast ribosome profiling
data.
AB - Ribosome profiling has emerged as a powerful technique to study mRNA translation.
Ribosome profiling has the potential to determine the relative quantities and
locations of ribosomes on mRNA genome wide. Taking full advantage of this
approach requires accurate measurement of ribosome locations. However,
experimental inconsistencies often obscure the positional information encoded in
ribosome profiling data. Here, we describe the Ribodeblur pipeline, a
computational analysis tool that uses a maximum likelihood framework to infer
ribosome positions from heterogeneous datasets. Ribodeblur is simple to install,
and can be run on an average modern Mac or Linux-based laptop. We detail the
process of applying the pipeline to high-coverage ribosome profiling data in
yeast, and discuss important considerations for potential extension to other
organisms.
PMID- 29330117
TI - RIFM fragrance ingredient safety assessment phenethyl isovalerate, CAS Registry
Number 140-26-1.
PMID- 29330119
TI - Temporal changes of the bacterial community colonizing wheat straw in the cow
rumen.
AB - This study used Miseq pyrosequencing and scanning electron microscopy to
investigate the temporal changes in the bacterial community tightly attached to
wheat straw in the cow rumen. The wheat straw was incubated in the rumens and
samples were recovered at various times. The wheat straw degradation exhibited
three phases: the first degradation phase occurred within 0.5 h, and the second
degradation phase occurred after 6 h, with a stalling phase occurring between 0.5
and 6 h. Scanning electron microscopy revealed the colonization of the
microorganisms on the wheat straw over time. The bacterial communities at 0.5, 6,
24, and 72 h were determined, corresponding to the degradation phases. Firmicutes
and Bacteroidetes were the two most dominant phyla in the bacterial communities
at the four time points. Principal coordinate analysis (PCoA) showed that the
bacterial communities at the four time points were distinct from each other. The
wheat straw-associated bacteria stabilized at the phylum level after 0.5 h of
rumen incubation, and only modest phylum-level and family-level changes were
observed for most taxa between 0.5 h and 72 h. The relative abundance of the
dominant genera, Butyrivibrio, Coprococcus, Ruminococcus, Succiniclasticum,
Clostridium, Prevotella, YRC22, CF231, and Treponema, changed significantly over
time (P < .05). However, at the genus level, unclassified taxa accounted for
70.3% +/- 6.1% of the relative abundance, indicating their probable importance in
the degradation of wheat straw as well as in the temporal changes of the
bacterial community. Thus, understanding the function of these unclassified taxa
is of great importance for targeted improvement of forage use efficiency in
ruminants. Collectively, our results revealed distinct degradation phases of
wheat straw and corresponding changes in the colonized bacterial community.
PMID- 29330120
TI - An update on the role of nanovehicles in nose-to-brain drug delivery.
AB - A quantitative analysis has cast doubt over the limited advantages provided by
particles for nose-to-brain (NTB) drug delivery. Thus, it is imperative to
identify the role of nanovehicles in NTB drug delivery. If nanocarriers are used
merely as an option to improve various properties of the drugs or the
formulations, it is difficult for them to outperform conventional formulations,
such as solutions or gels. However, nanovehicles bring about special features,
such as maintenance of the solubilized state of drugs, sustained or delayed
release, and enhanced penetration because of surface modifications, all of which
lead to enhanced NTB delivery efficiency.
PMID- 29330121
TI - Using network-based expert engagement to advance pharmaceutical research and
development.
PMID- 29330122
TI - Privileged portal metastasis of hepatocellular carcinoma in light of the
coevolution of a visceral portal system and liver in the chordate lineage: a
search for therapeutic targets.
AB - Hepatocellular carcinoma (HCC) disseminates systemically, but metastases occur in
distant organs only in minority of patients, whereas HCC routinely metastasizes
to liver and its vessels. HCC cells disseminate via hepatic veins, but portal
veins are affected by metastasis more frequently than are hepatic veins, and
correlates with poor prognosis. In this review, I suggest that privileged HCC
portal metastasis occurs because of high levels of pancreatic family hormones and
growth factors (PHGFs) in the portal blood. The analysis suggests that the
appearance of the portal system carrying PHGFs in the evolution of invertebrate
chordate (Amphioxus) led to the evolution of the liver in vertebrate; given that
the portal pattern of HCC metastasis and selection of more-aggressive clones are
PHGF dependent, PHGFs and their ligands constitute therapeutic targets.
PMID- 29330124
TI - Manipulating the epigenome for the treatment of disorders with thrombotic
complications.
AB - The haemostatic system is tightly regulated to maintain homeostasis to avoid
unwanted bleeding or thrombotic complications. Recent research has highlighted
the importance of epigenetic changes, such as DNA methylation, histone
modifications, and miRNA-based mechanisms, that alter gene expression. This can
give rise to dysregulated haemostatic or vascular expressed molecules
contributing to the development of thrombotic complications. Targeting these
epigenetic changes could provide a new avenue for the treatment of pathological
blood clots. However, the lack of tissue specificity warrants high-resolution
genomic studies of the transcriptome and methylome that will reveal explicit
epigenetic targets for the design of superior drugs with minimum off-target
effects.
PMID- 29330125
TI - The hitchhiker's guide to the chemical-biological galaxy.
AB - We are used to considering chemical and biological spaces as two different
entities; although they represent a more-interconnected world, in fact they
represent a Yin-Yang concept in drug discovery. Chemical-biological space is as
vast as the universe and, as Douglas Adams famously said, 'Space is big. You just
won't believe how vastly, hugely, mind-bogglingly big it is'. However, many
researchers are convinced that it is not so infinite, and are designing
computational and experimental tools to help identify and explore all possible
chemical-biological space. Here, we provide an analysis of their approaches and
discuss possible future research studies.
PMID- 29330123
TI - A bibliometric review of drug repurposing.
AB - We have conducted a bibliometric review of drug repurposing by scanning >25
million papers in PubMed and using text-mining methods to gather, count and
analyze chemical-disease therapeutic relationships. We find that >60% of the
~35,000 drugs or drug candidates identified in our study have been tried in more
than one disease, including 189 drugs that have been tried in >300 diseases each.
Whereas in the majority of cases these drugs were applied in therapeutic areas
close to their original use, there have been striking, and perhaps instructive,
successful attempts of drug repurposing for unexpected, novel therapeutic areas.
PMID- 29330126
TI - Recent progress in the discovery of myeloid differentiation 2 (MD2) modulators
for inflammatory diseases.
AB - Myeloid differentiation protein 2 (MD2), together with Toll-like receptor 4
(TLR4), binds lipopolysaccharide (LPS) with high affinity, inducing the formation
of the activated homodimer LPS-MD2-TLR4. MD2 directly recognizes the Lipid A
domain of LPS, leading to the activation of downstream signaling of cytokine and
chemokine production, and initiation of inflammatory and immune responses.
However, excessive activation and potent host responses generate severe
inflammatory syndromes such as acute sepsis and septic shock. MD2 is increasingly
being considered as an attractive pharmacological target for the development of
potent anti-inflammatory agents. In this Keynote review, we provide a
comprehensive overview of the recent advances in the structure and biology of
MD2, and present MD2 modulators as promising agents for anti-inflammatory
intervention.
PMID- 29330127
TI - Present drug-likeness filters in medicinal chemistry during the hit and lead
optimization process: how far can they be simplified?
AB - During the past decade, decreasing the attrition rate of drug development
candidates reaching the market has become one of the major challenges in
pharmaceutical research and drug development (R&D). To facilitate the decision
making process, and to increase the probability of rapidly finding and developing
high-quality compounds, a variety of multiparametric guidelines, also known as
rules and ligand efficiency (LE) metrics, have been developed. However, what are
the 'best' descriptors and how far can we simplify these drug-likeness prediction
tools in terms of the numerous, complex properties that they relate to?
PMID- 29330128
TI - Exploiting ion channel structure to assess rare variant pathogenicity.
AB - BACKGROUND: A 27-year-old woman was seen for long QT syndrome. She was found to
be a carrier of 2 variants, KCNQ1 Val162Met and KCNH2 Ser55Leu, and both were
classified as "pathogenic" by a diagnostic laboratory, in part because of
sequence proximity to other known pathogenic variants. OBJECTIVE: The purpose of
this study was to assess the relationship between both the KCNQ1 and KCNH2
variants and clinical significance using protein structure, in vitro functional
assays, and familial segregation. METHODS: We used co-segregation analysis of
family, patch clamp in vitro electrophysiology, and structural analysis using
recently released cryo-electron microscopy structures of both channels. RESULTS:
The structural analysis indicates that KCNQ1 Val162Met is oriented away from
functionally important regions while Ser55Leu is positioned at domains critical
for KCNH2 fast inactivation. Clinical phenotyping and electrophysiology study
further support the conclusion that KCNH2 Ser55Leu is correctly classified as
pathogenic but KCNQ1 Val162Met is benign. CONCLUSION: Proximity in sequence space
does not always translate accurately to proximity in 3-dimensional space.
Emerging structural methods will add value to pathogenicity prediction.
PMID- 29330129
TI - Estradiol up-regulates L-type Ca2+ channels via membrane-bound estrogen
receptor/phosphoinositide-3-kinase/Akt/cAMP response element-binding protein
signaling pathway.
AB - BACKGROUND: In long QT syndrome type 2, women are more prone than men to the
lethal arrhythmia torsades de pointes. We previously reported that 17beta
estradiol (E2) up-regulates L-type Ca2+ channels and current (ICa,L) (~30%) in
rabbit ventricular myocytes by a classic genomic mechanism mediated by estrogen
receptor-alpha (ERalpha). In long QT syndrome type 2 (IKr blockade or
bradycardia), the higher Ca2+ influx via ICa,L causes Ca2+ overload, spontaneous
sarcoplasmic reticulum Ca2+ release, and reactivation of ICa,L that triggers
early afterdepolarizations and torsades de pointes. OBJECTIVE: The purpose of
this study was to investigate the molecular mechanisms whereby E2 up-regulates
ICa,L, which are poorly understood. METHODS: H9C2 and rat myocytes were incubated
with E2 +/- ER antagonist, or inhibitors of downstream transcription factors, for
24 hours, followed by western blots of Cav1.2alpha1C and voltage-clamp
measurements of ICa,L. RESULTS: Incubation of H9C2 cells with E2 (10-100 nM)
increased ICa,L density and Cav1.2alpha1C expression, which were suppressed by
the ER antagonist ICI182,780 (1 MUM). Enhanced ICa,L and Cav1.2alpha1C expression
by E2 was suppressed by inhibitors of phosphoinositide-3-kinase (Pi3K) (30 MUM
LY294002; P <.05) and Akt (5 MUM MK2206) but not of mitogen-activated protein
kinase (5 MUM U0126) or protein kinase A (1 MUM KT5720). E2 incubation increased
p-CREB via the Pi3K/Akt pathway, reached a peak in 20 minutes (3-fold), and
leveled off to 1.5-fold 24 hours later. Furthermore, a CREB decoy oligonucleotide
inhibited E2-induced Cav1.2alpha1C expression, whereas membrane-impermeable E2
(E2-bovine serum albumin) was equally effective at Cav1.2alpha1C up-regulation as
E2. CONCLUSION: Estradiol up-regulates Cav1.2alpha1C and ICa,L via plasma
membrane ER and by activating Pi3K, Akt, and CREB signaling. The promoter regions
of the CACNA1C gene (human-rabbit-rat) contain adjacent/overlapping binding sites
for p-CREB and ERalpha, which suggests a synergistic regulation by these
pathways.
PMID- 29330130
TI - Perioperative electrophysiology study in patients with tetralogy of Fallot
undergoing pulmonary valve replacement will identify those at high risk of
subsequent ventricular tachycardia.
AB - BACKGROUND: Ventricular tachyarrhythmias are the most common cause of death in
patients with repaired tetralogy of Fallot (TOF), but predicting those at risk
remains a challenge. An electrophysiology study (EPS) has been proposed to risk
stratify patients with TOF. OBJECTIVE: We sought to evaluate a perioperative EPS
guided approach to risk stratify patients with TOF undergoing pulmonary valve
replacement (PVR) and guide concomitant cryoablation. METHODS: A prospective
cohort study of patients with TOF undergoing an EPS at the time of PVR from 2006
to 2017 was conducted at 2 centers. Patients inducible at the time of pre-PVR had
undergone concomitant cryoablation in addition to PVR. A repeat post-PVR EPS was
performed in those initially inducible to guide implantable cardioverter
defibrillator (ICD) implantation. RESULTS: Of 70 patients who underwent a pre-PVR
EPS, 34 (49%) had inducible sustained ventricular tachycardia (VT): 25
monomorphic VT and 9 polymorphic VT. Among patients undergoing cryoablation, 14
(45%) had inducible VT and underwent ICD implantation. During a mean follow-up
period of 6.1 +/- 3.2 years, 3 patients (21%) had appropriate ICD shocks for
symptomatic VT. There was an average of 2.3 shocks (range 1-4 shocks), and the
mean time to first shock post-device implantation was 3.6 years (range 2.9-4.3
years). Among patients with negative pre- or post-PVR EPS results, 2 had VT
requiring radiofrequency ablation and/or subsequent ICD implantation. There were
no arrhythmic deaths. CONCLUSION: A pre-PVR EPS identified patients with higher
risk TOF undergoing PVR. Despite empirical VT cryoablation at the time of PVR, a
high percentage of patients remained inducible for VT. In this high-risk cohort,
post-PVR EPS evaluation is important to identify patients at risk of VT despite
cryoablation.
PMID- 29330131
TI - Response of human induced pluripotent stem cell-derived cardiomyocytes to several
pharmacological agents when intrinsic syncytial pacing is overcome by acute
external stimulation.
AB - We challenged human induced pluripotent stem cell-derived cardiomyocyte (hiPSC
CM) syncytia, mainly, CDI iCells with several classes of well-characterized
pharmacological agents (including hERG blocker, Nav1.5 blocker, Cav1.2 blocker
and opener, beta-adrenergic agonist, and If blocker) under pacing conditions,
utilizing the Cardio-ECR instrument, a non-invasive platform featuring
simultaneous and continuous measurement of synchronized beating rate and
contractility (both signals were acquired simultaneously and well aligned). We
found that: 1) with increasing acute stimulation rates (no pacing; 1, 1.5, and
2Hz), beat interval was gradually shortened mainly in the relaxation phase of
each beat cycle; 2) typical responses of iCells hiPSC-CMs to all tested
pharmacological agents were either attenuated or even eliminated by pacing, in a
concentration- and stimulation rate-dependent manner; and 3) when iCells were
influenced by pharmacological agents and cannot follow pacing rates, they still
beat regularly at exactly 1/2 or 1/3 of pacing rates. We concluded that when
intrinsic syncytial pacing was overcome by faster, external stimulations, beat
intervals of hiPSC-CMs were mainly shortened in the relaxation phase, instead of
proportionally in each beat cycle, with increasing pacing rates. In addition, in
response to pharmacological agents upon pacing, hiPSC-CMs exhibited distinct
patterns of refractoriness, manifested by skipped beats in pacing-rate dependent
manner, and attenuation (or even abolition) of the typical response evoked under
spontaneous beating.
PMID- 29330132
TI - An overview of the safety pharmacology society strategic plan.
AB - Safety Pharmacology studies are conducted to characterize the confidence by which
biologically active new chemical entities (NCE) may be anticipated as safe. Non
clinical safety pharmacology studies aim to detect and characterize potentially
undesirable pharmacodynamic activities using an array of in silico, in vitro and
in vivo animal models. While a broad spectrum of methodological innovation and
advancement of the science occurs within the Safety Pharmacology Society, the
society also focuses on partnerships with health authorities and technology
providers and facilitates interaction with organizations of common interest such
as pharmacology, physiology, neuroscience, cardiology and toxicology. Education
remains a primary emphasis for the society through content derived from regional
and annual meetings, webinars and publication of its works it seeks to inform the
general scientific and regulatory community. In considering the future of safety
pharmacology the society has developed a strategy to successfully navigate
forward and not be mired in stagnation of the discipline. Strategy can be defined
in numerous ways but generally involves establishing and setting goals,
determining what actions are needed to achieve those goals, and mobilizing
resources within the society to accomplish the actions. The discipline remains in
rapid evolution and its coverage is certain to expand to provide better guidance
for more systems in the next few years. This overview from the Safety
Pharmacology Society will outline the strategic plan from 2016 to 2018 and beyond
and provide insight into the future of the discipline which builds upon a
previous strategic plan established in 2009.
PMID- 29330133
TI - The evaluation of drug-induced changes in left ventricular function in
pentobarbital-anesthetized dogs.
AB - INTRODUCTION: The goal of this study was to determine whether assessment of
myocardial contractility and hemodynamics in an anesthetized dog model, could
consistently detect drug-induced changes in the inotropic state of the heart
using drugs known to have clinically relevant positive and negative effects on
myocardial contractility. METHODS: Derived parameters included: diastolic,
systolic and mean arterial BP, peak systolic LVP, HR, end-diastolic LVP, and
LVdP/dtmax as the primary contractility index. RESULTS: These results demonstrate
that statistically significant increases (amrinone and pimobendan) and decreases
(atenolol and itraconazole) in left ventricular dP/dtmax were observed at
clinically relevant exposures. DISCUSSION: The analysis from the current study
supports the strategic use of the anesthetized dog model early in the drug
Discovery process for a comprehensive cardiovascular evaluation that can include
left ventricular dP/dtmax with good translation to human.
PMID- 29330134
TI - A supplementary functional connectivity microstate attached to the default mode
network in depression revealed by resting-state magnetoencephalography.
AB - Default mode network (DMN) has discernable involvement in the representation of
negative, self-referential information in depression. Both increased and
decreased resting-state functional connectivity between the anterior and
posterior DMN have been observed in depression. These conflicting connectivity
differences necessitated further exploration of the resting-state DMN dysfunction
in depression. Hence, we investigated the time-varying dynamic interactions
within the DMN via functional connectivity microstates in a sub-second level. 25
patients with depression and 25 matched healthy controls were enrolled in the MEG
analysis. Spherical K-means algorithms embedded within an iterative optimization
frame were applied to sliding windowed correlation matrices, resulting in sub
second alternations of two functional connectivity microstates for groups and
highlighting the presence of functional variability. In the power dominant state,
depressed patients showed a transient decreased pattern that reflected
inter/intra-subnetwork deregulation. A supplementary negatively correlated state
simultaneously presented with increased connectivity between the ventromedial
prefrontal cortex (vmPFC) and the posterior cingulate cortex (PCC), two core
nodes for the anterior and posterior DMN respectively. Additionally, depressed
patients stayed longer in the supplementary microstate compared to healthy
controls. During the time spent in the supplementary microstate, an attempt to
compensate for the aberrant effect of vmPFC on PCC across DMN subnetworks was
possibly made to balance the self-related processes disturbed by the dominant
pattern. The functional compensation mechanism of the supplementary microstate
attached to the dominant disrupted one provided a possible explanation to the
existing inconsistent findings between the anterior and posterior DMN in
depression.
PMID- 29330135
TI - APBB2 is associated with amphetamine use and plasma beta-amyloids in patients
receiving methadone maintenance treatment.
AB - APBB2, amyloid beta (A4) precursor protein-binding family B member 2, has been
reported to be associated with opioid dependence. In this study, we reported the
first time that the genetic variants in the APBB2 gene were associated with use
of amphetamine in opioid dependent patients undergoing methadone maintenance
treatment (MMT). 344 heroin-dependent patients undergoing MMT were recruited and
assessed for use of amphetamine and opioids by urine toxicology, withdrawal
severity, and side effects. DNAs were genome-widely genotyped for all patients.
Single nucleotide polymorphisms (SNPs) in APBB2 were selected for association
analyses for methadone treatment responses. Gene expression levels of APBB2 were
measured by real-time polymerase chain reaction (PCR) in the EBV-transformed
lymphoblastoids from patients. MMT patients who used amphetamine showed a
significantly higher percentage of positive results in the urine morphine test
(P=0.005), and insomnia (P=0.018). In single locus association analyses, SNPs
rs3935357 and rs4861075 located at intron 6 were significantly associated with
amphetamine use in both genotype and allele type (general linear model (GLM),
P=0.0003, and 0.0002 for genotype, and 0.0003, and 0.002 for allele type,
respectively). The major allele type carriers had twice risk of amphetamine use
compared to the minor allele type carriers. Subjects with the TT genotype of
rs4861075 showed significantly higher levels of APBB2 gene expression in both
total (P=0.02) and long-form (P=0.037) than those with CC genotype. Detailed
mechanisms underlying the association of APBB2 with amphetamine use and level of
plasma amyloid beta in MMT patients require further investigation.
PMID- 29330136
TI - White matter volume loss in amyotrophic lateral sclerosis: A meta-analysis of
voxel-based morphometry studies.
AB - Structural neuroimaging studies of white matter (WM) volume in amyotrophic
lateral sclerosis (ALS) using voxel-based morphometry (VBM) have yielded
inconsistent findings. This study aimed to perform a quantitative voxel-based
meta-analysis using effect-size signed differential mapping (ES-SDM) to establish
a statistical consensus between published studies for WM volume alterations in
ALS. The pooled meta-analysis revealed significant WM volume losses in the
bilateral supplementary motor areas (SMAs), bilateral precentral gyri (PGs), left
middle cerebellar peduncle and right cerebellum in patients with ALS, involving
the corticospinal tract (CST), interhemispheric fibers, subcortical arcuate
fibers, projection fibers to the striatum and cortico-ponto-cerebellar tract. The
meta-regression showed that the ALS functional rating scale-revised (ALSFRS-R)
was positively correlated with decreased WM volume in the bilateral SMAs, whereas
illness duration was negatively correlated with WM volume reduction in the right
SMA. This study provides a thorough profile of WM volume loss in ALS and robust
evidence that ALS is a multisystem neurodegenerative disease that involves a
variety of subcortical WM tracts extending beyond motor cortex involvement.
PMID- 29330137
TI - The intersection of stress and reward: BNST modulation of aversive and appetitive
states.
AB - The bed nucleus of the stria terminalis (BNST) is widely acknowledged as a brain
structure that regulates stress and anxiety states, as well as aversive and
appetitive behaviours. The diverse roles of the BNST are afforded by its highly
modular organisation, neurochemical heterogeneity, and complex intrinsic and
extrinsic circuitry. There has been growing interest in the BNST in relation to
psychopathologies such as anxiety and addiction. Although research on the human
BNST is still in its infancy, there have been extensive preclinical studies
examining the molecular signature and hodology of the BNST and their involvement
in stress and reward seeking behaviour. This review examines the neurochemical
phenotype and connectivity of the BNST, as well as electrophysiological
correlates of plasticity in the BNST mediated by stress and/or drugs of abuse.
PMID- 29330138
TI - A biogeographic and ecological perspective to the evolution of reproductive
behaviour in the family Salamandridae.
AB - Amphibians have a complex reproductive behaviour, which shows the highest
diversity among tetrapodes. The family Salamandridae, distributed across the
entire Holarctic, is one of the most diverse groups of extant salamanders
comprising 114 species in 21 genera. The family has a remarkable diversity of
courtship modes, amplexus and sperm transfer. It is often hypothesised that this
diversity has evolved in adaptation to a specific mating and/or breeding habitat.
We test this hypothesis based upon a phylogenetic reconstruction using the
complete mitochondrial genome sequences of 45 Salamandridae species, representing
all existing genera. We used ancestral character state reconstruction methods and
geographic range models and applied relaxed Bayesian molecular clock models to
discuss the results in a temporal framework of Salamandridae evolution. Our
results show that the family Salamandridae started to diversify in the Late
Cretaceous (ca. 87 mya) and is of Western Palearctic origin. Ancestral character
state reconstruction predicts that its common ancestor was oviparous, mated on
land without amplexus and probably showed a pin wheel spermatophore transfer,
which is still found in the Italian endemic Salamandrina terdigidata. Our results
suggest that several colonization of continents with subsequent radiations took
place, once to the Nearctic and twice into Eastern Asian realms. However, these
events were only in one case associated with a change in mating behaviour (dorsal
amplexus in Nearctic newts). Around the Cretaceous-Paleogene boundary (K-Pg
boundary) several Salamandridae lineages further diverged, again with no obvious
changes in mating behaviour. Overall, there is no significant signal for mating
character evolution being caused by changes in habitat type, with only a slight
tendency that changes in mating habitat might have led to changes in the type of
sperm transfer which in turn was associated with changes in the presence or
absence of amplexus.
PMID- 29330139
TI - Phylogenomics offers resolution of major tunicate relationships.
AB - Tunicata, a diverse clade of approximately 3000 described species of marine,
filter-feeding chordates, is of great interest to researchers because tunicates
are the closest living relatives of vertebrates and they facilitate comparative
studies of our own biology. The group also includes numerous invasive species
that cause considerable economic damage and some species of tunicates are edible.
Despite their diversity and importance, relationships among major lineages of
Tunicata are not completely resolved. Here, we supplemented public data with
transcriptomes from seven species spanning the diversity of Tunicata and
conducted phylogenomic analyses on data sets of up to 798 genes. Sensitivity
analyses were employed to examine the influences of reducing compositional
heterogeneity and branch-length heterogeneity. All analyses maximally supported a
monophyletic Tunicata within Olfactores (Vertebrata + Tunicata). Within Tunicata,
all analyses recovered Appendicularia sister to the rest of Tunicata and
confirmed (with maximal support) that Thaliacea is nested within Ascidiacea.
Stolidobranchia is the sister taxon to all other tunicates except Appendicularia.
In most analyses, phlebobranch tunicates were recovered paraphyletic with respect
to Aplousobranchia. Support for this topology varied but was strong in some
cases. However, when only the 50 best genes based on compositional heterogeneity
were analysed, we recovered Phlebobranchia and Aplousobranchia reciprocally
monophyletic with strong support, consistent with most traditional morphology
based hypotheses. Examination of internode certainty also cast doubt on results
of phlebobranch paraphyly, which may be due to limited taxon sampling. Taken
together, these results provide a higher-level phylogenetic framework for our
closest living invertebrate relatives.
PMID- 29330140
TI - Exploring Entertainment Medicine and Professionalization of Self-Care: Interview
Study Among Doctors on the Potential Effects of Digital Self-Tracking.
AB - BACKGROUND: Nowadays, digital self-tracking devices offer a plethora of
possibilities to both healthy and chronically ill users who want to closely
examine their body. This study suggests that self-tracking in a private setting
will lead to shifting understandings in professional care. To provide more
insight into these shifts, this paper seeks to lay bare the promises and
challenges of self-tracking while staying close to the everyday professional
experience of the physician. OBJECTIVE: The aim of this study was to (1) offer an
analysis of how medical doctors evaluate self-tracking methods in their practice
and (2) explore the anticipated shifts that digital self-care will bring about in
relation to our findings and those of other studies. METHODS: A total of 12 in
depth semistructured interviews with general practitioners (GPs) and
cardiologists were conducted in Flanders, Belgium, from November 2015 to November
2016. Thematic analysis was applied to examine the transcripts in an iterative
process. RESULTS: Four major themes arose in our body of data: (1) the patient as
health manager, (2) health obsession and medicalization, (3) information
management, and (4) shifting roles of the doctors and impact on the health care
organization. Our research findings show a nuanced understanding of the
potentials and pitfalls of different forms of self-tracking. The necessity of
contextualization of self-tracking data and a professionalization of self-care
through digital devices come to the fore as important overarching concepts.
CONCLUSIONS: This interview study with Belgian doctors examines the potentials
and challenges of self-monitoring while focusing on the everyday professional
experience of the physician. The dialogue between our dataset and the existing
literature affords a fine-grained image of digital self-care and its current
meaning in a medical-professional landscape.
PMID- 29330141
TI - Novel Care Pathway for Patients Presenting to the Emergency Department With
Atrial Fibrillation.
PMID- 29330142
TI - Checklists and Circulation: Cardiovascular Quality and Outcomes.
PMID- 29330143
TI - Breast Cancer Targeting through Inhibition of the Endoplasmic Reticulum-Based
Apoptosis Regulator Nrh/BCL2L10.
AB - Drug resistance and metastatic relapse remain a top challenge in breast cancer
treatment. In this study, we present preclinical evidence for a strategy to
eradicate advanced breast cancers by targeting the BCL-2 homolog Nrh/BCL2L10,
which we discovered to be overexpressed in >45% of a large cohort of breast
invasive carcinomas. Nrh expression in these tumors correlated with reduced
metastasis-free survival, and we determined it to be an independent marker of
poor prognosis. Nrh protein localized to the endoplasmic reticulum. Mechanistic
investigations showed that Nrh made BH4 domain-dependent interactions with the
ligand-binding domain of the inositol-1,4,5-triphosphate receptor (IP3R), a type
1/3 Ca2+ channel, allowing Nrh to negatively regulate ER-Ca2+ release and to
mediate antiapoptosis. Notably, disrupting Nrh/IP3R complexes by BH4 mimetic
peptides was sufficient to inhibit the growth of breast cancer cells in vitro and
in vivo Taken together, our results highlighted Nrh as a novel prognostic marker
and a candidate therapeutic target for late stage breast cancers that may be
addicted to Nrh.Significance: These findings offer a comprehensive molecular
model for the activity of Nrh/BCL2L10, a little studied antiapoptotic molecule,
prognostic marker, and candidate drug target in breast cancer. Cancer Res; 78(6);
1404-17. (c)2018 AACR.
PMID- 29330145
TI - MBD2 Ablation Impairs Lymphopoiesis and Impedes Progression and Maintenance of T
ALL.
AB - Aberrant DNA methylation patterns in leukemia might be exploited for therapeutic
targeting. In this study, we employed a genetically deficient mouse model to
explore the role of the methylated DNA binding protein MBD2 in normal and
malignant hematopoiesis. MBD2 ablation led to diminished lymphocytes. Functional
defects of the lymphoid compartment were also observed after in vivo
reconstitution of MBD2-deficient hematopoietic stem cells (HSC). In an
established model of Notch1-driven T-cell acute lymphoblastic leukemia (T-ALL),
MBD2 ablation impeded malignant progression and maintenance by attenuating the
Wnt signaling pathway. In clinical specimens of human T-ALL, Wnt signaling
pathway signatures were significantly enhanced and positively correlated with the
expression and function of MBD2. Furthermore, a number of typical Wnt signaling
inhibitory genes were abnormally hypermethylated in primary human T-ALL. Abnormal
activation of Wnt signaling in T-ALL was switched off by MBD2 deletion, partially
by reactivating epigenetically silenced Wnt signaling inhibitors. Taken together,
our results define essential roles for MBD2 in lymphopoiesis and T-ALL and
suggest MBD2 as a candidate therapeutic target in T-ALL.Significance: This study
highlights a methylated DNA binding protein as a candidate therapeutic target to
improve the treatment of T-cell acute lymphoblastic leukemias, as a new starting
point for developing epigenetic therapy in this and other lymphoid malignancies.
Cancer Res; 78(7); 1632-42. (c)2018 AACR.
PMID- 29330146
TI - Demethylation-Induced Overexpression of Shc3 Drives c-Raf-Independent Activation
of MEK/ERK in HCC.
AB - Invasion and intrahepatic metastasis are major factors of poor prognosis in
patients with hepatocellular carcinoma (HCC). In this study, we show that
increased Src homolog and collagen homolog 3 (Shc3) expression in malignant HCC
cell lines associate with HCC invasion and metastasis. Shc3 (N-Shc) was
significantly upregulated in tumors of 33 HCC patient samples as compared with
adjacent normal tissues. Further analysis of 52 HCC patient samples showed that
Shc3 expression correlated with microvascular invasion, cancer staging, and poor
prognosis. Shc3 interacted with major vault protein, resulting in activation of
MEK1/2 and ERK1/2 independently of Shc1 and c-Raf; this interaction consequently
induced epithelial-mesenchymal transition and promoted HCC cell proliferation and
metastasis. The observed increase in Shc3 levels was due to demethylation of its
upstream promoter, which allowed c-Jun binding. In turn, Shc3 expression promoted
c-Jun phosphorylation in a positive feedback loop. Analysis of metastasis using a
tumor xenograft mouse model further confirmed the role of Shc3 in vivo Taken
together, our results indicate the importance of Shc3 in HCC progression and
identify Shc3 as a novel biomarker and potential therapeutic target in
HCC.Significance: Ectopic expression of Shc3 forms a complex with MVP/MEK/ERK to
potentiate ERK activation and plays an important role in sorafinib resistance in
HCC. Cancer Res; 78(9); 2219-32. (c)2018 AACR.
PMID- 29330144
TI - Kindlin-1 Promotes Pulmonary Breast Cancer Metastasis.
AB - In breast cancer, increased expression of the cytoskeletal adaptor protein
Kindlin-1 has been linked to increased risks of lung metastasis, but the
functional basis is unknown. Here, we show that in a mouse model of polyomavirus
middle T antigen-induced mammary tumorigenesis, loss of Kindlin-1 reduced early
pulmonary arrest and later development of lung metastasis. This phenotype relied
on the ability of Kindlin-1 to bind and activate beta integrin heterodimers.
Kindlin-1 loss reduced alpha4 integrin-mediated adhesion of mammary tumor cells
to the adhesion molecule VCAM-1 on endothelial cells. Treating mice with an anti
VCAM-1 blocking antibody prevented early pulmonary arrest. Kindlin-1 loss also
resulted in reduced secretion of several factors linked to metastatic spread,
including the lung metastasis regulator tenascin-C, showing that Kindlin-1
regulated metastatic dissemination by an additional mechanism in the tumor
microenvironment. Overall, our results show that Kindlin-1 contributes
functionally to early pulmonary metastasis of breast cancer.Significance: These
findings provide a mechanistic proof in mice that Kindin-1, an integrin-binding
adaptor protein, is a critical mediator of early lung metastasis of breast
cancer. Cancer Res; 78(6); 1484-96. (c)2018 AACR.
PMID- 29330147
TI - Genetic Ablation of Rbm38 Promotes Lymphomagenesis in the Context of Mutant p53
by Downregulating PTEN.
AB - Mutant p53 exerts gain-of-function effects that drive metastatic progression and
therapeutic resistance, but the basis for these effects remain obscure. The RNA
binding protein RBM38 limits translation of mutant p53 and is often altered in
tumors harboring it. Here we show how loss of Rbm38 significantly alters cancer
susceptibility in mutant p53 knock-in mice by shortening lifespan, altering tumor
incidence, and promoting T-cell lymphomagenesis. Loss of Rbm38 enhanced mutant
p53 expression and decreased expression of the tumor suppressor Pten, a key
regulator of T-cell development. Furthermore, Rbm38 was required for Pten
expression via stabilization of Pten mRNA through an AU-rich element in its
3'UTR. Our results suggest that Rbm38 controls T-cell lymphomagenesis by jointly
modulating mutant p53 and Pten, with possible therapeutic implications for
treating T-cell malignancies.Significance: An RNA-binding protein controls T-cell
lymphomagenesis by jointly modulating mutant p53 and PTEN, with possible
therapeutic implications for treating T-cell malignancies. Cancer Res; 78(6);
1511-21. (c)2018 AACR.
PMID- 29330148
TI - Correction.
PMID- 29330149
TI - Voluntary exercise and depression-like behavior in rodents: are we running in the
right direction?
AB - Acute or chronic exposure to stress can increase the risk to develop major
depressive disorder, a severe, recurrent and common psychiatric condition.
Depression places an enormous social and financial burden on modern society.
Although many depressed patients are treated with antidepressants, their efficacy
is only modest, underscoring the necessity to develop clinically effective
pharmaceutical or behavioral treatments. Exercise training produces beneficial
effects on stress-related mental disorders, indicative of clinical potential. The
pro-resilient and antidepressant effects of exercise training have been
documented for several decades. Nonetheless, the underlying molecular mechanisms
and the brain circuitries involved remain poorly understood. Preclinical
investigations using voluntary wheel running, a frequently used rodent model that
mimics aspects of human exercise training, have started to shed light on the
molecular adaptations, signaling pathways and brain nuclei underlying the
beneficial effects of exercise training on stress-related behavior. In this
review, I highlight several neurotransmitter systems that are putative mediators
of the beneficial effects of exercise training on mental health, and review
recent rodent studies that utilized voluntary wheel running to promote our
understanding of exercise training-induced central adaptations. Advancements in
our mechanistic understanding of how exercise training induces beneficial
neuronal adaptations will provide a framework for the development of new
strategies to treat stress-associated mental illnesses.
PMID- 29330150
TI - Dysfunctional signaling underlying endometriosis: current state of knowledge.
AB - Endometriosis is defined as the presence of endometrial tissue outside the
uterine cavity. It affects approximately 5-10% of women of reproductive age.
Endometriosis is associated with dysmenorrhea, dyspareunia and, often, severe
pelvic pain. In addition to pain, women with endometriosis often experience
infertility. Defining the molecular etiology of endometriosis is a significant
challenge for improving the quality of women's lives. Unfortunately, the
pathophysiology of endometriosis is not well understood. Here, we summarize the
potential causative factors of endometriosis in the following three categories:
(1) dysregulation of immune cells in the peritoneal fluid and endometriotic
lesions; (2) alteration of apoptotic signaling in retrograde menstrual tissue and
cytotoxic T cells involved in endometriosis progression and (3) dysregulation of
oxidative stress. Determining the molecular etiology of these dysregulated
cellular signaling pathways should provide crucial clues for understanding
initiation and progression of endometriosis. Moreover, improved understanding
should suggest new molecular therapeutic targets that could improve the
specificity of endometriosis treatments and reduce the side effects associated
with current approaches.
PMID- 29330151
TI - Interleukin-22 reverses human islet dysfunction and apoptosis triggered by
hyperglycemia and LIGHT.
AB - Interleukin (IL)-22 has recently been suggested as an anti-inflammatory cytokine
that could protect the islet cells from inflammation- and glucose-induced
toxicity. We have previously shown that the tumor necrosis factor family member,
LIGHT, can impair human islet function at least partly via pro-apoptotic effects.
Herein, we aimed to investigate the protective role of IL-22 on human islets
exposed to the combination of hyperglycemia and LIGHT. First, we found
upregulation of LIGHT receptors (LTbetaR and HVEM) in engrafted human islets
exposed to hyperglycemia (>11 mM) for 17 days post transplantation by using a
double islet transplantation mouse model as well as in human islets cultured with
high glucose (HG) (20 mM glucose) + LIGHT in vitro, and this latter effect was
attenuated by IL-22. The effect of HG + LIGHT impairing glucose-stimulated
insulin secretion was reversed by IL-22. The harmful effect of HG + LIGHT on
human islet function seemed to involve enhanced endoplasmic reticulum stress
evidenced by upregulation of p-IRE1alpha and BiP, elevated secretion of pro
inflammatory cytokines (IL-6, IL-8, IP-10 and MCP-1) and the pro-coagulant
mediator tissue factor (TF) release and apoptosis in human islets, whereas all
these effects were at least partly reversed by IL-22. Our findings suggest that
IL-22 could counteract the harmful effects of LIGHT/hyperglycemia on human islet
cells and potentially support the strong protective effect of IL-22 on impaired
islet function and survival.
PMID- 29330152
TI - Risk of Infection in Type 1 and Type 2 Diabetes Compared With the General
Population: A Matched Cohort Study.
AB - OBJECTIVE: We describe in detail the burden of infections in adults with diabetes
within a large national population cohort. We also compare infection rates
between patients with type 1 and type 2 diabetes mellitus (T1DM and T2DM).
RESEARCH DESIGN AND METHODS: A retrospective cohort study compared 102,493
English primary care patients aged 40-89 years with a diabetes diagnosis by 2008
(n = 5,863 T1DM and n = 96,630 T2DM) with 203,518 age-sex-practice-matched
control subjects without diabetes. Infection rates during 2008-2015, compiled
from primary care and linked hospital and mortality records, were compared across
19 individual infection categories. These were further summarized as any
requiring a prescription or hospitalization or as cause of death. Poisson
regression was used to estimate incidence rate ratios (IRRs) between 1) people
with diabetes and control subjects and 2) T1DM and T2DM adjusted for age, sex,
smoking, BMI, and deprivation. RESULTS: Compared with control subjects without
diabetes, patients with diabetes had higher rates for all infections, with the
highest IRRs seen for bone and joint infections, sepsis, and cellulitis. IRRs for
infection-related hospitalizations were 3.71 (95% CI 3.27-4.21) for T1DM and 1.88
(95% CI 1.83-1.92) for T2DM. A direct comparison of types confirmed higher
adjusted risks for T1DM versus T2DM (death from infection IRR 2.19 [95% CI 1.75
2.74]). We estimate that 6% of infection-related hospitalizations and 12% of
infection-related deaths were attributable to diabetes. CONCLUSIONS: People with
diabetes, particularly T1DM, are at increased risk of serious infection,
representing an important population burden. Strategies that reduce the risk of
developing severe infections and poor treatment outcomes are under-researched and
should be explored.
PMID- 29330153
TI - Heart Failure in Pregnant Women: A Concern Across the Pregnancy Continuum.
AB - BACKGROUND: Heart failure (HF) is a leading cause of maternal morbidity and
mortality in the United States, but prevalence, correlates, and outcomes of HF
related hospitalization during antepartum, delivery, and postpartum periods
remain unknown. The objective was to examine HF prevalence, correlates, and
outcomes among pregnancy-related hospitalizations among women 13 to 49 years of
age. METHODS AND RESULTS: We used the 2001 to 2011 Nationwide Inpatient Sample.
Rates of HF were calculated by patient and hospital characteristics. Survey
logistic regression was used to estimate adjusted odds ratios representing the
association between HF and each outcome, stratified by antepartum, delivery, and
postpartum periods. Joinpoint regression was used to describe temporal trends in
HF and in-hospital mortality. Over 50 million pregnancy-related hospitalizations
were analyzed. The overall rate of HF was 112 cases per 100 000 pregnancy-related
hospitalizations. Although postpartum encounters represented only 1.5% of
pregnancy-related hospitalizations, ~60% of HF cases occurred postpartum,
followed by delivery (27.3%) and antepartum (13.2%). Among postpartum
hospitalizations, there was a significant 7.1% (95% confidence interval, 4.4-9.8)
annual increase in HF from 2001 to 2006, followed by a steady rate through 2011.
HF rates among antepartum hospitalizations increased on average 4.9% (95%
confidence interval, 3.0-6.8) annually from 2001 to 2011. Women with a diagnosis
of HF were more likely to experience adverse maternal outcomes, as reflected by
outcome-specific adjusted odds ratios during antepartum (2.7-25), delivery (6
195), and postpartum (1.5-6.6) periods. CONCLUSIONS: HF is associated with
increased risk of maternal mortality and morbidities. During hospitalization,
high-risk mothers need to be identified and surveillance programs developed
before discharge.
PMID- 29330154
TI - Novel Wearable Seismocardiography and Machine Learning Algorithms Can Assess
Clinical Status of Heart Failure Patients.
AB - BACKGROUND: Remote monitoring of patients with heart failure (HF) using wearable
devices can allow patient-specific adjustments to treatments and thereby
potentially reduce hospitalizations. We aimed to assess HF state using wearable
measurements of electrical and mechanical aspects of cardiac function in the
context of exercise. METHODS AND RESULTS: Patients with compensated (outpatient)
and decompensated (hospitalized) HF were fitted with a wearable ECG and
seismocardiogram sensing patch. Patients stood at rest for an initial recording,
performed a 6-minute walk test, and then stood at rest for 5 minutes of recovery.
The protocol was performed at the time of outpatient visit or at 2 time points
(admission and discharge) during an HF hospitalization. To assess patient state,
we devised a method based on comparing the similarity of the structure of
seismocardiogram signals after exercise compared with rest using graph mining
(graph similarity score). We found that graph similarity score can assess HF
patient state and correlates to clinical improvement in 45 patients (13
decompensated, 32 compensated). A significant difference was found between the
groups in the graph similarity score metric (44.4+/-4.9 [decompensated HF] versus
35.2+/-10.5 [compensated HF]; P<0.001). In the 6 decompensated patients with
longitudinal data, we found a significant change in graph similarity score from
admission (decompensated) to discharge (compensated; 44+/-4.1 [admitted] versus
35+/-3.9 [discharged]; P<0.05). CONCLUSIONS: Wearable technologies recording
cardiac function and machine learning algorithms can assess compensated and
decompensated HF states by analyzing cardiac response to submaximal exercise.
These techniques can be tested in the future to track the clinical status of
outpatients with HF and their response to pharmacological interventions.
PMID- 29330155
TI - Amlexanox Inhibits Cerebral Ischemia-Induced Delayed Astrocytic High-Mobility
Group Box 1 Release and Subsequent Brain Damage.
AB - High-mobility group box 1 (HMGB1) is increased in the cerebrospinal fluid (CSF)
and serum during the early and late phases of brain ischemia and is known to
contribute to brain damage. However, detailed characterization underlying cell
type-specific HMGB1 release and pathophysiological roles of extracellularly
released HMGB1 in ischemic brain remain unclear. Here, we examined cell type
specific HMGB1 release and the therapeutic potential of amlexanox, an inhibitor
of nonclassical release, and of an anti-HMGB1 antibody against ischemic brain
damage. HMGB1 depletion from neuronal nuclei was observed within 3 hours after
transient middle cerebral artery occlusion (tMCAO), whereas the
intracerebroventricular (i.c.v.) pretreatment with amlexanox blocked HMGB1
release from neurons, resulting in HMGB1 redistribution in the nuclei and
cytoplasm. HMGB1 was selectively released from astrocytes 27 hours after tMCAO
and this HMGB1 release was blocked by late treatment with amlexanox (i.c.v.) 24
hours after tMCAO. Proximity extension assay revealed that the HMGB1 level was
elevated in the CSF at 3 and 27 hours after tMCAO. This late treatment with
amlexanox significantly protected the brain from ischemic damage, but its
pretreatment 30 minutes before tMCAO failed to show any protection. The late
treatment (i.c.v.) with anti-HMGB1 antibody 24 hours after tMCAO also ameliorated
ischemic brain damage 48 hours after tMCAO. Thus, the inhibition of brain damage
by late treatment with amlexanox or anti-HMGB1 antibody indicates that late HMGB1
release plays a role in the maintenance of stroke-induced brain damage, and the
inhibition of this release would be a novel therapeutic target for protection of
ischemic brain damage.
PMID- 29330157
TI - Measuring the prevention of harm due to minimum alcohol pricing.
PMID- 29330156
TI - Application of Receptor Theory to the Design and Use of Fixed-Proportion Mu
Opioid Agonist and Antagonist Mixtures in Rhesus Monkeys.
AB - Receptor theory predicts that fixed-proportion mixtures of a competitive,
reversible agonist (e.g., fentanyl) and antagonist (e.g., naltrexone) at a common
receptor [e.g., mu-opioid receptors (MORs)] will result in antagonist proportion
dependent decreases in apparent efficacy of the agonist/antagonist mixtures and
downward shifts in mixture dose-effect functions. The present study tested this
hypothesis by evaluating behavioral effects of fixed-proportion
fentanyl/naltrexone mixtures in a warm-water tail-withdrawal procedure in rhesus
monkeys (n = 4). Fentanyl (0.001-0.056 mg/kg) alone, naltrexone (0.032-1.0 mg/kg,
i.m.) alone, and fixed-proportion mixtures of fentanyl/naltrexone (1:0.025,
1:0.074, and 1:0.22) were administered in a cumulative-dosing procedure, and the
proportions were based on published fentanyl and naltrexone Kd values at MOR in
monkey brain. Fentanyl alone produced dose-dependent antinociception at both 50
and 54 degrees C thermal intensities. Up to the largest dose tested, naltrexone
alone did not alter nociception. Consistent with receptor theory predictions,
naltrexone produced a proportion-dependent decrease in the effectiveness of
fentanyl/naltrexone mixtures to produce antinociception. The maximum effects of
fentanyl, naltrexone, and each mixture were also used to generate an efficacy
effect scale for antinociception at each temperature, and this scale was
evaluated for its utility in quantifying 1) efficacy requirements for
antinociception at 50 and 54 degrees C and 2) relative efficacy of six MOR
agonists that vary in their efficacies to produce agonist-stimuated GTPgammaS
binding in vitro (from lowest to highest efficacy: 17-cyclopropylmethyl-3,14beta
dihyroxy-4,5alpha-epoxy-6alpha-[(3'-isoquinolyl)acetamindo]morphine, nalbuphine,
buprenorphine, oxycodone, morphine, and methadone). These results suggest that
fixed-proportion agonist/antagonist mixtures may offer a useful strategy to
manipulate apparent drug efficacy for basic research or therapeutic purposes.
PMID- 29330159
TI - Commercial influence in control of non-communicable diseases.
PMID- 29330160
TI - US is the most dangerous wealthy nation for a child to be born into, study
concludes.
PMID- 29330163
TI - Affective stimuli in behavioural interventions soliciting for health check-up
services and the service users' socioeconomic statuses: a study at Japanese
pachinko parlours.
AB - : Editor's note The study reported in this article examines a health intervention
that uses gendered stereotypes of the nursing profession and suggestive uniforms
that play on women's sexuality to encourage people to engage in health checkups.
The intervention was not under the control of the authors and the study was
approved by an institutional research ethics board. The Journal of Epidemiology &
Community Health condemns the use of sexism, gender and professional stereotypes
and other forms of discriminatory or exploitative behaviour for any purpose,
including health promotion programs. In light of concerns raised about this paper
(see eLetters with this paper), we are conducting an audit of our review process
and will put in place measures to ensure that the material we publish condemns
sexism, racism and other forms of discrimination and embodies principles of
inclusion and non-discrimination. BACKGROUND: Socioeconomically vulnerable people
are likely to have more health risks because of inadequate behaviour choices
related to chronic social stresses. Brain science suggests that stress causes
cognitively biased automatic decision making, preferring instant stress relief
and pleasure (eg, smoking, alcohol use and drug abuse) as opposed to reflectively
seeking health-maintenance services (eg, health check-ups). As such, hedonic
stimuli that nudge people towards preventive actions could reduce health
behaviour disparities. The purpose of this intervention study was to test this
hypothesis. METHODS: An instant health check-up service company had 320 health
check-up sessions at pachinko (Japanese gambling) parlours; 1721 persons in
intervention sessions and 6507 persons in control sessions received the service.
The stimuli the company used in the intervention sessions were young women
wearing mildly erotic nurse costumes, who solicited the pachinko players for
health check-up services. We compared the prevalence of socioeconomically
vulnerable individuals between the intervention and control sessions, adjusting
for individual-level and parlour-level potential confounders. RESULTS: Even
adjusting for health risks and within-parlour clustering, the intervention
sessions gathered more socioeconomically vulnerable customers than the regular
sessions. Compared with control sessions, in intervention sessions the adjusted
prevalence ratios were 1.15 (95% CI 0.99 to 1.35) for not having a job (vs having
a job) and 1.36 (95% CI 1.00 to 1.86) for holders of National Health Insurance
(which includes more socially vulnerable people than other insurance programmes).
CONCLUSION: The results supported our hypothesis. Offering health check-up
opportunities equipped with 'tricks' that nudge people to act might be effective
for anyone but is potentially more valuable for socially vulnerable people.
Ethical discussions are needed to further consider the use of erotic stimuli and
other essential drivers of human behaviour.
PMID- 29330162
TI - Transcriptome Analyses of Mosaic (MSC) Mitochondrial Mutants of Cucumber in a
Highly Inbred Nuclear Background.
AB - Cucumber (Cucumis sativus L.) has a large, paternally transmitted mitochondrial
genome. Cucumber plants regenerated from cell cultures occasionally show
paternally transmitted mosaic (MSC) phenotypes, characterized by slower growth,
chlorotic patterns on the leaves and fruit, lower fertility, and rearrangements
in their mitochondrial DNAs (mtDNAs). MSC lines 3, 12, and 16 originated from
different cell cultures all established using the highly inbred, wild-type line
B. These MSC lines possess different rearrangements and under-represented regions
in their mtDNAs. We completed RNA-seq on normalized and non-normalized cDNA
libraries from MSC3, MSC12, and MSC16 to study their nuclear gene-expression
profiles relative to inbred B. Results from both libraries indicated that gene
expression in MSC12 and MSC16 were more similar to each other than MSC3. Forty
one differentially expressed genes (DEGs) were upregulated and one downregulated
in the MSC lines relative to B. Gene functional classifications revealed that
more than half of these DEGs are associated with stress-response pathways.
Consistent with this observation, we detected elevated levels of hydrogen
peroxide throughout leaf tissue in all MSC lines compared to wild-type line B.
These results demonstrate that independently produced MSC lines with different
mitochondrial polymorphisms show unique and shared nuclear responses. This study
revealed genes associated with stress response that could become selection
targets to develop cucumber cultivars with increased stress tolerance, and
further support of cucumber as a model plant to study nuclear-mitochondrial
interactions.
PMID- 29330161
TI - Production of BMP4 by endothelial cells is crucial for endogenous thymic
regeneration.
AB - The thymus is not only extremely sensitive to damage but also has a remarkable
ability to repair itself. However, the mechanisms underlying this endogenous
regeneration remain poorly understood, and this capacity diminishes considerably
with age. We show that thymic endothelial cells (ECs) comprise a critical pathway
of regeneration via their production of bone morphogenetic protein 4 (BMP4) ECs
increased their production of BMP4 after thymic damage, and abrogating BMP4
signaling or production by either pharmacologic or genetic inhibition impaired
thymic repair. EC-derived BMP4 acted on thymic epithelial cells (TECs) to
increase their expression of Foxn1, a key transcription factor involved in TEC
development, maintenance, and regeneration, and its downstream targets such as
Dll4, a key mediator of thymocyte development and regeneration. These studies
demonstrate the importance of the BMP4 pathway in endogenous tissue regeneration
and offer a potential clinical approach to enhance T cell immunity.
PMID- 29330164
TI - Public health guide to field developments linking ecosystems, environments and
health in the Anthropocene.
AB - The impacts of global environmental change have precipitated numerous approaches
that connect the health of ecosystems, non-human organisms and humans. However,
the proliferation of approaches can lead to confusion due to overlaps in
terminology, ideas and foci. Recognising the need for clarity, this paper
provides a guide to seven field developments in environmental public health
research and practice: occupational and environmental health; political ecology
of health; environmental justice; ecohealth; One Health; ecological public
health; and planetary health. Field developments are defined in terms of their
uniqueness from one another, are historically situated, and core texts or
journals are highlighted. The paper ends by discussing some of the intersecting
features across field developments, and considers opportunities created through
such convergence. This field guide will be useful for those seeking to build a
next generation of integrative research, policy, education and action that is
equipped to respond to current health and sustainability challenges.
PMID- 29330165
TI - Survival in relation to multimorbidity patterns in older adults in primary care
in Barcelona, Spain (2010-2014): a longitudinal study based on electronic health
records.
AB - BACKGROUND: Several studies have analysed the characteristics of multimorbidity
patterns but none have evaluated the relationship with survival. The purpose of
this study was to compare survival across older adults with different chronic
multimorbidity patterns (CMPs). METHODS: Prospective longitudinal observational
study using electronic health records for 190 108 people aged >=65 years in
Barcelona, Spain (2009-2014). CMPs were identified by cluster analysis. Mortality
rates were estimated using the Catalan population structure and individual time
at risk. Survival according to CMP (Cox regression) was analysed using hazard
ratios (HRs) and 95% confidence intervals (CIs) with stratification by sex and
age group (65-79, 80-94) and adjustment for age at onset, deprivation index,
number of chronic conditions and invoiced drugs. RESULTS: The highest mortality
rates were observed in men, adults aged 80-94 years, socially disadvantaged
quintiles and people prescribed more drugs and with fewer conditions. Using the
musculoskeletal pattern as the reference category, men with the digestive
respiratory pattern had a higher risk of death, with adjusted HRs of 6.16 (95% CI
5.37 to 7.06) in the 65-79 age group and 2.62 (95% CI 2.31 to 2.97) in the 80-94
age group. In women, the cardiovascular pattern was associated with the highest
risk, with adjusted HRs of 6.34 (95% CI 5.28 to 7.61) in the 65-79 age group and
3.05 (95% CI 2.73 to 3.41) in the 80-94 age group. These patterns were also
associated with the highest mortality rates. CONCLUSIONS: Mortality and survival
vary according to CMPs in older adults stratified by sex and age. Our findings
are useful for guiding the design and implementation of clinical management
strategies.
PMID- 29330166
TI - Impact of free access to leisure facilities and community outreach on
inequalities in physical activity: a quasi-experimental study.
AB - BACKGROUND: There are large inequalities in levels of physical activity in the
UK, and this is an important determinant of health inequalities. Little is known
about the effectiveness of community-wide interventions to increase physical
activity and whether effects differ by socioeconomic group. METHODS: We conducted
interrupted time series and difference-in-differences analyses using local
administrative data and a large national survey to investigate the impact of an
intervention providing universal free access to leisure facilities alongside
outreach and marketing activities in a deprived local authority area in the
northwest of England. Outcomes included attendances at swimming and gym sessions,
self-reported participation in gym and swim activity and any physical activity.
RESULTS: The intervention was associated with a 64% increase in attendances at
swimming and gym sessions (relative risk 1.64, 95% CI 1.43 to 1.89, P<0.001), an
additional 3.9% of the population participating in at least 30 min of moderate
intensity gym or swim sessions during the previous four weeks (95% CI 3.6 to 4.1)
and an additional 1.9% of the population participating in any sport or active
recreation of at least moderate intensity for at least 30 min on at least 12 days
out of the last four weeks (95% CI 1.7 to 2.1). The effect on gym and swim
activity and overall levels of participation in physical activity was
significantly greater for the more disadvantaged socioeconomic group.
CONCLUSIONS: The study suggests that removing user charges from leisure
facilities in combination with outreach and marketing activities can increase
overall population levels of physical activity while reducing inequalities.
PMID- 29330167
TI - Differences in declining mortality rates due to coronary heart disease by
neighbourhood deprivation.
AB - BACKGROUND: Cardiovascular disease (CVD) is the main cause of death in most
industrialised countries, including those in Europe. The mortality rates due to
coronary heart disease (CHD), one of the most serious CVD conditions, have been
decreasing in most European countries during the last decades. However, whether
the trends over time in CHD mortality rates differ depending on neighbourhood
deprivation has rarely been investigated. METHODS: For each year of the study
period, 1988-2012, in Sweden, age-standardised mortality rates were calculated
for three different types of neighbourhoods, characterised by a Neighbourhood
Deprivation Index. Joinpoint regression was used to investigate potential changes
in age-standardised mortality rates by neighbourhood deprivation and over time.
RESULTS: Over the study period, age-standardised mortality rates due to CHD were
consistently the highest in the deprived neighbourhoods and the lowest in the
affluent neighbourhoods. We observed a statistically significant overall decline,
ranging from 67% to 59%, in the age-standardised CHD mortality rates for each
level of neighbourhood deprivation. Furthermore, the decline for the affluent
neighbourhoods was significantly higher compared with the decline in the deprived
neighbourhoods. CONCLUSION: Age-standardised CHD mortality rates decreased
significantly in Sweden between 1988 and 2012. This decline was more pronounced
in the affluent neighbourhoods, which indicates that the improvements in
prevention and treatment of CHD have not benefited individuals residing in
deprived neighbourhoods to an equal extent. Knowledge of time trends in CHD
mortality by level of neighbourhood deprivation may help guide decision-makers in
the development of appropriate healthcare policies for deprived neighbourhoods.
PMID- 29330169
TI - Inter-rater reliability in the Paediatric Observation Priority Score (POPS).
AB - OBJECTIVE: The primary objective of this study was to determine the level of
inter-rater reliability between nursing staff for the Paediatric Observation
Priority Score (POPS). DESIGN: Retrospective observational study. SETTING: Single
centre paediatric emergency department. PARTICIPANTS: 12 participants from a
convenience sample of 21 nursing staff. INTERVENTIONS: Participants were shown
video footage of three pre-recorded paediatric assessments and asked to record
their own POPS for each child. The participants were blinded to the original, in
person POPS. Further data were gathered in the form of a questionnaire to
determine the level of training and experience the candidate had using the POPS
score prior to undertaking this study. MAIN OUTCOME MEASURES: Inter-rater
reliability among participants scoring of the POPS. RESULTS: Overall kappa value
for case 1 was 0.74 (95% CI 0.605 to 0.865), case 2 was 1 (perfect agreement) and
case 3 was 0.66 (95% CI 0.58 to 0.744). CONCLUSION: This study suggests there is
good inter-rater reliability between different nurses' use of POPS in assessing
sick children in the emergency department.
PMID- 29330170
TI - Retrospective review of Synacthen testing in infants.
AB - BACKGROUND: A subnormal cortisol response (30 min level (C30min)<550 nmol/L) to
synthetic adrenocorticotrophic hormone/Synacthen test (SDST) in all infants does
not necessarily indicate underlying or persistent hypothalamic-pituitary-adrenal
axis pathology. METHODS: We retrospectively evaluated the diagnoses and outcomes
in 68 infants who had a SDST at age <6 months from 2011 to 2014. RESULTS: 29
(43%) infants had a subnormal SDST. Causative pathology was identified in 9/29
(31%). In 20/29 (69%) with no identified pathology, repeat SDST was normal in
18/20 (90%) at median age 0.6 (range 0.1-3.2) years but persistently subnormal in
2. Those with a transient abnormality were more likely to be small for
gestational age (P=0.03) and had higher initial SDST C30min (390 nmol/L vs 181
nmol/L, P=0.01) than those with pathology. CONCLUSION: Specific aetiology can be
identified in a third of infants with a subnormal SDST. When the aetiology
remains elusive, adrenal function should be reassessed as the problem can be
transient.
PMID- 29330168
TI - MRB7260 is essential for productive protein-RNA interactions within the RNA
editing substrate binding complex during trypanosome RNA editing.
AB - The trypanosome RNA editing substrate binding complex (RESC) acts as the platform
for mitochondrial uridine insertion/deletion RNA editing and facilitates the
protein-protein and protein-RNA interactions required for the editing process.
RESC is broadly comprised of two subcomplexes: GRBC (guide RNA binding complex)
and REMC (RNA editing mediator complex). Here, we characterize the function and
position in RESC organization of a previously unstudied RESC protein, MRB7260. We
show that MRB7260 forms numerous RESC-related complexes, including a novel, small
complex with the guide RNA binding protein, GAP1, which is a canonical GRBC
component, and REMC components MRB8170 and TbRGG2. RNA immunoprecipitations in
MRB7260-depleted cells show that MRB7260 is critical for normal RNA trafficking
between REMC and GRBC. Analysis of protein-protein interactions also reveals an
important role for MRB7260 in promoting stable association of the two
subcomplexes. High-throughput sequencing analysis of RPS12 mRNAs from MRB7260
replete and depleted cells demonstrates that MRB7260 is critical for gRNA
exchange and early gRNA utilization, with the exception of the initiating gRNA.
Together, these data demonstrate that MRB7260 is essential for productive protein
RNA interactions with RESC during RNA editing.
PMID- 29330171
TI - Historic child sexual abuse: have we got it right?
PMID- 29330172
TI - Origins of tobacco harm reduction in the UK: the 'Product Modification Programme'
(1972-1991).
AB - OBJECTIVE: To better understand the current embrace of long-term nicotine
maintenance by British governmental agencies and tobacco harm reduction by
several leading British public health organisations, describe the context and
deliberations of the UK's first formal tobacco risk reduction programme: 'Product
Modification'. METHODS: Analysis of previously secret tobacco industry documents,
news archives and Parliamentary debate records. RESULTS: From 1972 to 1991, the
British government sought to investigate safer smoking through the 'product
modification programme'. The Independent Scientific Committee on Smoking and
Health (ISCSH) advised the British government on these efforts and collaborated
with the tobacco industry, with which government then negotiated to determine
policy. The ISCSH operated from four industry-backed premises, which contributed
to the ISCSH's support of safer smoking: (1) reduced toxicity indicates reduced
risk; (2) collaboration with the tobacco industry will not undermine tobacco
control; (3) nicotine addiction is unavoidable; (4) to curtail cigarette use,
solutions must be consumer-approved (ie, profitable). These premises often
undermined tobacco control efforts and placed the ISCSH at odds with broader
currents in public health. The product modification programme was abandoned in
1991 as the European Community began requiring members to adopt upper tar limits,
rendering the ISCSH redundant. POLICY IMPLICATIONS: Endorsements of reduced harm
tobacco products share the same four premises that supported the product
modification programme. Current tobacco harm reduction premises and policies
supported by the British government and leading British public health
organisations may reflect the historical influence of the tobacco industry.
PMID- 29330173
TI - Seasonal variations in tuberculosis diagnosis among HIV-positive individuals in
Southern Africa: analysis of cohort studies at antiretroviral treatment
programmes.
AB - OBJECTIVES: Seasonal variations in tuberculosis diagnoses have been attributed to
seasonal climatic changes and indoor crowding during colder winter months. We
investigated trends in pulmonary tuberculosis (PTB) diagnosis at antiretroviral
therapy (ART) programmes in Southern Africa. SETTING: Five ART programmes
participating in the International Epidemiology Database to Evaluate AIDS in
South Africa, Zambia and Zimbabwe. PARTICIPANTS: We analysed data of 331 634 HIV
positive adults (>15 years), who initiated ART between January 2004 and December
2014. PRIMARY OUTCOME MEASURE: We calculated aggregated averages in monthly
counts of PTB diagnoses and ART initiations. To account for time trends, we
compared deviations of monthly event counts to yearly averages, and calculated
correlation coefficients. We used multivariable regressions to assess
associations between deviations of monthly ART initiation and PTB diagnosis
counts from yearly averages, adjusted for monthly air temperatures and
geographical latitude. As controls, we used Kaposi sarcoma and extrapulmonary
tuberculosis (EPTB) diagnoses. RESULTS: All programmes showed monthly variations
in PTB diagnoses that paralleled fluctuations in ART initiations, with recurrent
patterns across 2004-2014. The strongest drops in PTB diagnoses occurred in
December, followed by April-May in Zimbabwe and South Africa. This corresponded
to holiday seasons, when clinical activities are reduced. We observed little
monthly variation in ART initiations and PTB diagnoses in Zambia. Correlation
coefficients supported parallel trends in ART initiations and PTB diagnoses
(correlation coefficient: 0.28, 95% CI 0.21 to 0.35, P<0.001). Monthly
temperatures and latitude did not substantially change regression coefficients
between ART initiations and PTB diagnoses. Trends in Kaposi sarcoma and EPTB
diagnoses similarly followed changes in ART initiations throughout the year.
CONCLUSIONS: Monthly variations in PTB diagnosis at ART programmes in Southern
Africa likely occurred regardless of seasonal variations in temperatures or
latitude and reflected fluctuations in clinical activities and changes in health
seeking behaviour throughout the year, rather than climatic factors.
PMID- 29330174
TI - Views and experiences of seeking information and help for vitiligo: a qualitative
study of written accounts.
AB - OBJECTIVES: Vitiligo is a relatively common autoimmune condition causing loss of
skin pigment. Around 1 in 100 people in the UK develop vitiligo. It can have a
significant impact on quality of life for many of those affected. How people
access information and help for vitiligo may influence how they manage such
impact. We aimed to explore people's views and experiences of seeking health
information and help for vitiligo. DESIGN: Qualitative analysis of free-text
responses to four open-ended questions in an online survey. SETTING: Online
survey conducted in the UK between February and March 2016. PARTICIPANTS: A
survey link was emailed to 675 members of The Vitiligo Society, a UK-based
charity providing information and support for people with vitiligo. One hundred
and sixty-one members responded to the survey (24%). RESULTS: Many participants
wrote extensive free text, often reporting frustration with help-seeking. They
perceived general practitioners (GP) as their primary source of advice but felt
that GPs had low awareness of available treatments. Where GPs appeared
sympathetic or signposted towards further information this was appreciated, even
where people felt their GP had not seemed knowledgeable. Many felt that vitiligo
was dismissed by health professionals including GPs and dermatologists as
'cosmetic', which upset those who experienced substantial impact. Participants
expressed concerns about the credibility of online information on vitiligo and
the need for reliable, detailed information, as well as a desire for support with
managing its psychosocial impact. CONCLUSIONS: Information and help-seeking needs
of people with vitiligo currently appear to be poorly met, even among members of
The Vitiligo Society, who are likely to have received more information than
others. People with vitiligo would welcome greater health professional awareness
of available vitiligo treatments. Acknowledging the psychosocial impacts of
vitiligo and signposting towards credible information are also welcomed.
PMID- 29330175
TI - Development and validation of an instrument for measuring the burden of medicine
on functioning and well-being: the Medication-Related Burden Quality of Life (MRB
QoL) tool.
AB - OBJECTIVE: Medication-related burden (MRB) is a negative experience with
medicine, which may impact on psychological, social, physical and financial well
being of an individual. This study describes the development and initial
validation of an instrument specifically designed to measure MRB on functioning
and well-being-the Medication-Related Burden Quality of Life (MRB-QoL) tool.
METHODS: An initial pool of 76-items for MRB-QoL was generated. The link to MRB
QoL survey was sent to a sample of consumers living with at least one chronic
medical condition and taking >=3 prescription medicines on a regular basis.
Exploratory factor analysis (EFA) was used to determine the underlining factor
structure. Internal consistency (Cronbach's alpha) and construct validity were
examined. The latter was examined through correlation with Medication Regimen
Complexity Index (MRCI), Drug Burden Index (DBI) and Charlson's Comorbidity Index
(CCI). RESULTS: 367 consumers completed the survey (51.2% male). EFA resulted in
a 31-item, five-factor solution explaining 72% of the total variance. The five
subscales were labelled as 'Routine and Regimen Complexity' (11 items),
'Psychological Burden' (six items), 'Functional and Role Limitation' (seven
items), 'Therapeutic Relationship' (three items) and 'Social Burden' (four
items). All subscales showed good internal consistency (Cronbach's alpha 0.87 to
0.95). Discriminant validity of MRB-QoL was demonstrated via its correlations
with MRCI (Spearman's r -0.16 to 0.08), DBI (r 0.12 to 0.28) and CCI (r -0.23 to
0.15). Correlation between DBI and 'Functional and Role Limitation' subscale (r
0.36) indicated some evidence of convergent validity. Patients with polypharmacy,
multiple morbidity and DBI >0 had higher median scores of MRB-QoL providing
evidence for known group validity. CONCLUSIONS: The MRB-QoL V.1 has good
construct validity and internal consistency. The MRB-QoL may be a useful
humanistic measure for evaluating the impact of pharmaceutical care interventions
on patients' quality of life. Future research is warranted to further examine
additional psychometric properties of MRB-QoL V.1 and its utility in patient
care.
PMID- 29330176
TI - Therapists' experiences with a new treatment combining physical exercise and
dietary therapy (the PED-t) for eating disorders: an interview study in a
randomised controlled trial at the Norwegian School of Sport Sciences.
AB - OBJECTIVES: The aim of the current study is to explore how therapists running a
guided physical exercise and dietary therapy programme (PED-t) experience their
contribution to the treatment of patients with bulimia nervosa and binge eating
disorder. METHODS: Ten therapists running the PED-t were semistructurally
interviewed and the transcribed interviews were analysed using a systematic text
condensation approach. SETTING: The study was run within the context of a
randomised controlled trial at the Norwegian School of Sport Sciences. RESULTS:
The therapists experienced their knowledge about physical exercise and nutrition
as important and useful, and that they could share their knowledge with the
patients in different ways and with confidence in their own role. They also
believed that their knowledge could serve as tools for the patients' post
treatment recovery and management of their daily lives. Moreover, the therapists
put much effort in adjusting their teaching to fit each individual participant.
Finally, they reported their personal qualities as important to build trust and
therapeutic alliance. CONCLUSIONS: The terms 'clinical confidence' and 'alliance'
may stand out as the overarching 'metacategories' covering the experiences
revealed in this study. The clinical implication is that new groups of
professionals may have an important role in the treatment of eating disorders.
TRIAL REGISTRATION NUMBER: NCTO2079935; Results.
PMID- 29330177
TI - Incidence of Facultative Bacterial Endosymbionts in Spider Mites Associated with
Local Environments and Host Plants.
AB - Spider mites are frequently associated with multiple endosymbionts whose
infection patterns often exhibit spatial and temporal variation. However, the
association between endosymbiont prevalence and environmental factors remains
unclear. Here, we surveyed endosymbionts in natural populations of the spider
mite, Tetranychus truncatus, in China, screening 935 spider mites from 21
localities and 12 host plant species. Three facultative endosymbiont lineages,
Wolbachia, Cardinium, and Spiroplasma, were detected at different infection
frequencies (52.5%, 26.3%, and 8.6%, respectively). Multiple endosymbiont
infections were observed in most local populations, and the incidence of
individuals with the Wolbachia-Spiroplasma coinfection was higher than expected
from the frequency of each infection within a population. Endosymbiont infection
frequencies exhibited associations with environmental factors: Wolbachia
infection rates increased at localities with higher annual mean temperatures,
while Cardinium and Spiroplasma infection rates increased at localities from
higher altitudes. Wolbachia was more common in mites from Lycopersicon esculentum
and Glycine max compared to those from Zea mays This study highlights that host
endosymbiont interactions may be associated with environmental factors, including
climate and other geographically linked factors, as well as the host's food
plant.IMPORTANCE The aim of this study was to examine the incidence of
endosymbiont distribution and the infection patterns in spider mites. The main
findings are that multiple endosymbiont infections were more common than expected
and that endosymbiont infection frequencies were associated with environmental
factors. This work highlights that host-endosymbiont interactions need to be
studied within an environmental and geographic context.
PMID- 29330178
TI - Development of an Efficient Genome Editing Tool in Bacillus licheniformis Using
CRISPR-Cas9 Nickase.
AB - Bacillus strains are important industrial bacteria that can produce various
biochemical products. However, low transformation efficiencies and a lack of
effective genome editing tools have hindered its widespread application.
Recently, clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9
techniques have been utilized in many organisms as genome editing tools because
of their high efficiency and easy manipulation. In this study, an efficient
genome editing method was developed for Bacillus licheniformis using a CRISPR
Cas9 nickase integrated into the genome of B. licheniformis DW2 with
overexpression driven by the P43 promoter. The yvmC gene was deleted using the
CRISPR-Cas9n technique with homology arms of 1.0 kb as a representative example,
and an efficiency of 100% was achieved. In addition, two genes were
simultaneously disrupted with an efficiency of 11.6%, and the large DNA fragment
bacABC (42.7 kb) was deleted with an efficiency of 79.0%. Furthermore, the
heterologous reporter gene aprN, which codes for nattokinase in Bacillus
subtilis, was inserted into the chromosome of B. licheniformis with an efficiency
of 76.5%. The activity of nattokinase in the DWc9nDelta7/pP43SNT-SsacC strain
reached 59.7 fibrinolytic units (FU)/ml, which was 25.7% higher than that of
DWc9n/pP43SNT-SsacC Finally, the engineered strain DWc9nDelta7 (Deltaepr
DeltawprA Deltampr DeltaaprE Deltavpr DeltabprA DeltabacABC), with multiple
disrupted genes, was constructed using the CRISPR-Cas9n technique. Taken
together, we have developed an efficient genome editing tool based on CRISPR
Cas9n in B. licheniformis This tool could be applied to strain improvement for
future research.IMPORTANCE As important industrial bacteria, Bacillus strains
have attracted significant attention due to their production of biological
products. However, genetic manipulation of these bacteria is difficult. The
CRISPR-Cas9 system has been applied to genome editing in some bacteria, and
CRISPR-Cas9n was proven to be an efficient and precise tool in previous reports.
The significance of our research is the development of an efficient, more
precise, and systematic genome editing method for single-gene deletion, multiple
gene disruption, large DNA fragment deletion, and single-gene integration in
Bacillus licheniformis via Cas9 nickase. We also applied this method to the
genetic engineering of the host strain for protein expression.
PMID- 29330179
TI - Influence of type-I fimbriae and fluid shear stress on bacterial behavior and
multicellular architecture of early Escherichia coli biofilms at single-cell
resolution.
AB - Biofilm formation on abiotic surfaces in food and medical industry can cause
severe contamination and infection, yet how biological and physical factors
determine cellular architecture of early biofilms and bacterial behavior of the
constituent cells remains largely unknown. In this study we examine the specific
role of type-I fimbriae in nascent stages of biofilm formation and the response
of micro-colonies to environmental flow shear at single-cell resolution. The
results show that type-I fimbriae are not required for reversible adhesion from
plankton, but critical for irreversible adhesion of Escherichia coli (E.coli)
MG1655 forming biofilms on polyethylene terephthalate (PET) surfaces. Besides
establishing a firm cell-surface contact, the irreversible adhesion seems
necessary to initiate the proliferation of E.coli on the surface. After
application of shear stress, bacterial retention is dominated by the 3D
architecture of colonies independent of the population and the multi-layered
structure could protect the embedded cells from being insulted by fluid shear,
while cell membrane permeability mainly depends on the biofilm population and the
duration time of the shear stress.ImportanceBacterial biofilms could lead to
severe contamination problems in medical devices and food processing equipment.
However, biofilms are usually studied at a rough macroscopic level, thus little
is known about how individual bacterial behavior within biofilms and
multicellular architecture are influenced by bacterial appendages (e.g.
pili/fimbriae) and environmental factors during early biofilm formation. We apply
Confocal Laser Scanning Microscopy (CLSM) to visualize E.coli micro-colonies at
single-cell resolution. Our findings suggest that type-I fimbriae are vital to
the initiation of bacterial proliferation on surfaces and that the responses of
biofilm architecture and cell membrane permeability of constituent bacteria to
fluid shear stress are different, which are respectively regulated by the 3D
morphology and the population of micro-colonies.
PMID- 29330180
TI - Intraclade Variability in Toxin Production and Cytotoxicity of Bacillus cereus
Group Type Strains and Dairy-Associated Isolates.
AB - While some species in the Bacillus cereus group are well-characterized human
pathogens (e.g., B. anthracis and B. cereus sensu stricto), the pathogenicity of
other species (e.g., B. pseudomycoides) either has not been characterized or is
presently not well understood. To provide an updated characterization of the
pathogenic potential of species in the B. cereus group, we classified a set of 52
isolates, including 8 type strains and 44 isolates from dairy-associated sources,
into 7 phylogenetic clades and characterized them for (i) the presence of toxin
genes, (ii) phenotypic characteristics used for identification, and (iii)
cytotoxicity to human epithelial cells. Overall, we found that B. cereus toxin
genes are broadly distributed but are not consistently present within individual
species and/or clades. After growth at 37 degrees C, isolates within a clade did
not typically show a consistent cytotoxicity phenotype, except for isolates in
clade VI (B. weihenstephanensis/B. mycoides), where none of the isolates were
cytotoxic, and isolates in clade I (B. pseudomycoides), which consistently
displayed cytotoxic activity. Importantly, our study highlights that B.
pseudomycoides is cytotoxic toward human cells. Our results indicate that the
detection of toxin genes does not provide a reliable approach to predict the
pathogenic potential of B. cereus group isolates, as the presence of toxin genes
is not always consistent with cytotoxicity phenotype. Overall, our results
suggest that isolates from multiple B. cereus group clades have the potential to
cause foodborne illness, although cytotoxicity is not always consistently found
among isolates within each clade.IMPORTANCE Despite the importance of the
Bacillus cereus group as a foodborne pathogen, characterizations of the
pathogenic potential of all B. cereus group species were lacking. We show here
that B. pseudomycoides (clade I), which has been considered a harmless
environmental microorganism, produces toxins and exhibits a phenotype consistent
with the production of pore-forming toxins. Furthermore, B. mycoides/B.
weihenstephanensis isolates (clade VI) did not show cytotoxicity when grown at 37
degrees C, despite carrying multiple toxin genes. Overall, we show that the
current standard methods to characterize B. cereus group isolates and to detect
the presence of toxin genes are not reliable indicators of species, phylogenetic
clades, or an isolate's cytotoxic capacity, suggesting that novel methods are
still needed for differentiating pathogenic from nonpathogenic species within the
B. cereus group. Our results also contribute data that are necessary to
facilitate risk assessments and a better understanding as to which B. cereus
group species are likely to cause foodborne illness.
PMID- 29330181
TI - A Novel Corynebacterium glutamicum l-Glutamate Exporter.
AB - Besides metabolic pathways and regulatory networks, transport systems are also
pivotal for cellular metabolism and hyperproduction of biochemicals using
microbial cell factories. The identification and characterization of transporters
are therefore of great significance for the understanding and engineering of
transport reactions. Herein, a novel l-glutamate exporter, MscCG2, which exists
extensively in Corynebacterium glutamicum strains but is distinct from the only
known l-glutamate exporter, MscCG, was discovered in an industrial l-glutamate
producing C. glutamicum strain. MscCG2 was predicted to possess three
transmembrane helices in the N-terminal region and located in the cytoplasmic
membrane, which are typical structural characteristics of the mechanosensitive
channel of small conductance. MscCG2 has a low amino acid sequence identity (23%)
to MscCG and evolved separately from MscCG with four transmembrane helices.
Despite the considerable differences between MscCG2 and MscCG in sequence and
structure, gene deletion and complementation confirmed that MscCG2 also
functioned as an l-glutamate exporter and an osmotic safety valve in C.
glutamicum Besides, transcriptional analysis showed that MscCG2 and MscCG genes
were transcribed in similar patterns and not induced by l-glutamate-producing
conditions. It was also demonstrated that MscCG2-mediated l-glutamate excretion
was activated by biotin limitation or penicillin treatment and that constitutive
l-glutamate excretion was triggered by a gain-of-function mutation of MscCG2
(A151V). Discovery of MscCG2 will enrich the understanding of bacterial amino
acid transport and provide additional targets for exporter engineering.IMPORTANCE
The exchange of matter, energy, and information with surroundings is fundamental
for cellular metabolism. Therefore, studying transport systems that are essential
for these processes is of great significance. Besides, transport systems of
bacterial cells are usually related to product excretion as well as product
reuptake, making transporter engineering a useful strategy for strain
improvement. The significance of our research is in identifying and
characterizing a novel l-glutamate exporter from the industrial workhorse
Corynebacterium glutamicum, which will enrich the understanding of l-glutamate
excretion and provide a new target for studying bacterial amino acid transport
and engineering transport reactions.
PMID- 29330182
TI - Fluorescence Recovery Allows the Implementation of a Fluorescence Reporter Gene
Platform Applicable for the Detection and Quantification of Horizontal Gene
Transfer in Anoxic Environments.
AB - The study of horizontal gene transfer (HGT) in microbial communities has been
revolutionized by significant advances in cultivation-independent methods based
on fluorescence reporter gene technologies. Recently, the combination of these
novel approaches with flow cytometry has presented itself as one of the most
powerful tools to study the spread of mobile genetic elements (MGEs) in the
environment. However, the use of fluorescent markers, like green fluorescent
protein (GFP) and mCherry, is limited by environmental constraints, such as
oxygen availability and pH levels, that affect the correct maturation of their
fluorophores. Few studies have characterized the effects of such environmental
conditions in a systematic way, and the sheer amount of distinct protein variants
requires each system to be examined in an individual fashion. The lack of
efficient and reliable markers to monitor HGT in anaerobic environments, coupled
to the abundance of ecologically and clinically relevant oxygen-deprived niches
in which bacteria thrive, calls for the urgent development of suitable tools that
permit its study. In an attempt to devise a process that allows the
implementation of the mentioned dual-labeling system to anoxic milieus, the
aerobic fluorescence recovery of mCherry and GFPmut3, as well as the effect of pH
on their fluorescence intensities, was studied. The findings present a solution
to an intrinsic problem that has long hampered the utilization of this system,
highlight its pH limitations, and provide experimental tools that will help
broaden its horizon of application to other fields.IMPORTANCE Many anaerobic
environments, like the gastrointestinal tract, anaerobic digesters, and the
interiors of dense biofilms, have been shown to be hotspots for horizontal gene
transfer (HGT). Despite the increasing wealth of reports warning about the
alarming spread of antibiotic resistance determinants, to date, HGT studies
mainly rely on cultivation-based methods. Unfortunately, the relevance of these
studies is often questionable, as only a minor fraction of bacteria can be
cultivated. A recently developed approach to monitoring the fate of plasmids in
microbial communities is based on a fluorescence dual-labeling system and allows
the bypassing of cultivation. However, the fluorescent proteins on which it is
founded are constrained by pH levels and by their strict dependence on oxygen for
the maturation of their fluorophores. This study focused on the development and
validation of an appropriate aerobic fluorescence recovery (AFR) method for this
platform, as this embodies the missing technical link impeding its implementation
in anoxic environments.
PMID- 29330183
TI - Campylobacter jejuni Colonization in the Crow Gut Involves Many Deletions within
the Cytolethal Distending Toxin Gene Cluster.
AB - Campylobacter spp. are major causes of gastroenteritis worldwide. The virulence
potential of Campylobacter shed in crow feces obtained from a roost area in
Bothell, Washington, was studied and compared with that from isolates from other
parts of Washington and from a different crow species 7,000 miles away in
Kolkata, India. Campylobacter organisms were isolated from 61% and 69% of the
fecal samples obtained from Washington and Kolkata, respectively, and were
confirmed to be C. jejuni The cytolethal distending toxin (CDT) gene cluster from
these isolates revealed a truncated sequence of approximately 1,350 bp.
Sequencing of the gene cluster revealed two types of mutations: a 668-bp deletion
across cdtA and cdtB and a 51-bp deletion within cdtB Some strains had additional
20-bp deletions in cdtB In either case, a functional toxin is not expected; a
functional toxin is produced by the expression of three tandem genes, cdtA, cdtB,
and cdtC Reverse transcriptase PCR with total RNA extracted from the isolates
showed no expression of cdtB A toxin assay performed with these isolates on HeLa
cells failed to show cytotoxic effects on the cells. However, the isolates were
able to colonize the chicken ceca for a period of at least 4 weeks, similar to
that of a clinical isolate. Other virulence gene markers, flagellin A and CadF,
were present in 100% of the isolates. Our study suggests that crows carry the
bacterium C. jejuni but with a dysfunctional toxin protein that is expected to
drastically reduce its potential to cause diarrhea.IMPORTANCE Campylobacters are
a major cause of gastroenteritis in humans. Since outbreaks have most often been
correlated with poultry or unpasteurized dairy products, contact with farm
animals, or contaminated water, historically, the majority of the studies have
been with campylobacter isolates from poultry, domestic animals, and human
patients. However, the bacterium has a broad host range that includes birds.
These reservoirs need to be investigated, because the identification of the
source and a determination of the transmission routes for a pathogen are
important for the development of evidence-based disease control programs. In this
study, two species of the human-commensal crow, from two different geographical
regions separated by 7,000 miles of land and water, have been examined for their
ability to cause disease by shedding campylobacters. Our results show that the
crow may not play a significant role in campylobacteriosis, because the
campylobacter organisms they shed produce a nonfunctional toxin.
PMID- 29330184
TI - Microbiomes in Dishwashers: Analysis of the microbial diversity and putative
opportunistic pathogens in dishwasher biofilm communities.
AB - Extreme habitats are not only limited to natural environments, but also apply to
man-made systems, for instance household appliances such as dishwashers. Limiting
factors, such as high temperatures, high and low pH, high NaCl concentrations,
presence of detergents and shear force from water during washing cycles define
the microbial survival in this extreme system. Fungal and bacterial diversity in
biofilms isolated from rubber seals of 24 different household dishwashers were
investigated using next generation sequencing. Bacterial genera such as
Pseudomonas, Escherichia and Acinetobacter, known to include opportunistic
pathogens, were represented in most samples. The most frequently encountered
fungal genera in these samples belonged to Candida, Cryptococcus and Rhodotorula,
also known to include opportunistic pathogenic representatives. This study showed
how specific conditions of the dishwashers impact the abundance of microbial
groups, and investigated on the inter- and intra-kingdom interactions that shape
these biofilms. The age, the usage frequency and hardness of incoming tap water
of dishwashers had significant impact on bacterial and fungal composition.
Representatives of Candida spp. were found at highest prevalence (100%) in all
dishwashers and are assumingly one of the first colonizers in recent dishwashers.
Pairwise correlations in tested microbiome showed that certain bacterial groups
co-occur and so did the fungal groups. In mixed bacterial-fungal biofilms, early
adhesion, contact and interactions were vital in the process of biofilm
formation, where mixed complexes of the two, bacteria and fungi, could provide a
preliminary biogenic structure for the establishment of these biofilms.IMPORTANCE
Worldwide demand for household appliances, such as dishwashers and washing
machines, is increasing, as well as the number of immune-compromised individuals.
The harsh conditions in household dishwashers should prevent growth of most
microorganisms. However, our research shows that persisting poly-extremotolerant
groups of microorganisms in household appliances are well established under these
unfavourable conditions, supported by the biofilm mode of growth. The
significance of our research is in identifying the microbial composition of
biofilms formed on dishwasher rubber seals, how diverse abiotic conditions
affects microbiota and which key members were represented in early colonisation
and contamination of dishwashers, as these appliances can present a source of
domestic cross-contamination leading to broader medical impacts.
PMID- 29330185
TI - MgtE Homolog FicI Acts as a Secondary Ferrous Iron Importer in Shewanella
oneidensis Strain MR-1.
AB - The transport of metals into and out of cells is necessary for the maintenance of
appropriate intracellular concentrations. Metals are needed for incorporation
into metalloproteins but become toxic at higher concentrations. Many metal
transport proteins have been discovered in bacteria, including the Mg2+
transporter E (MgtE) family of passive Mg2+/Co2+ cation-selective channels. Low
sequence identity exists between members of the MgtE family, indicating that
substrate specificity may differ among MgtE transporters. Under anoxic
conditions, dissimilatory metal-reducing bacteria, such as Shewanella and
Geobacter species, are exposed to high levels of soluble metals, including Fe2+
and Mn2+ Here we characterize SO_3966, which encodes an MgtE homolog in
Shewanella oneidensis that we name FicI (ferrous iron and cobalt importer) based
on its role in maintaining metal homeostasis. A SO_3966 deletion mutant exhibits
enhanced growth over that of the wild type under conditions with high Fe2+ or
Co2+ concentrations but exhibits wild-type Mg2+ transport and retention
phenotypes. Conversely, deletion of feoB, which encodes an energy-dependent Fe2+
importer, causes a growth defect under conditions of low Fe2+ concentrations but
not high Fe2+ concentrations. We propose that FicI represents a secondary, less
energy-dependent mechanism for iron uptake by S. oneidensis under high Fe2+
concentrations.IMPORTANCEShewanella oneidensis MR-1 is a target of microbial
engineering for potential uses in biotechnology and the bioremediation of heavy
metal-contaminated environments. A full understanding of the ways in which S.
oneidensis interacts with metals, including the means by which it transports
metal ions, is important for optimal genetic engineering of this and other
organisms for biotechnology purposes such as biosorption. The MgtE family of
metal importers has been described previously as Mg2+ and Co2+ transporters. This
work broadens that designation with the discovery of an MgtE homolog in S.
oneidensis that imports Fe2+ but not Mg2+ The research presented here also
expands our knowledge of the means by which microorganisms have adapted to take
up essential nutrients such as iron under various conditions.
PMID- 29330186
TI - Effect of Plasmid Design and Type of Integration Event on Recombinant Protein
Expression in Pichia pastoris.
AB - Pichia pastoris (syn. Komagataella phaffii) is one of the most common eukaryotic
expression systems for heterologous protein production. Expression cassettes are
typically integrated in the genome to obtain stable expression strains. In
contrast to Saccharomyces cerevisiae, where short overhangs are sufficient to
target highly specific integration, long overhangs are more efficient in P.
pastoris and ectopic integration of foreign DNA can occur. Here, we aimed to
elucidate the influence of ectopic integration by high-throughput screening of
>700 transformants and whole-genome sequencing of 27 transformants. Different
vector designs and linearization approaches were used to mimic the most common
integration events targeted in P. pastoris Fluorescence of an enhanced green
fluorescent protein (eGFP) reporter protein was highly uniform among
transformants when the expression cassettes were correctly integrated in the
targeted locus. Surprisingly, most nonspecifically integrated transformants
showed highly uniform expression that was comparable to specific integration,
suggesting that nonspecific integration does not necessarily influence
expression. However, a few clones (<10%) harboring ectopically integrated
cassettes showed a greater variation spanning a 25-fold range, surpassing
specifically integrated reference strains up to 6-fold. High-expression strains
showed a correlation between increased gene copy numbers and high reporter
protein fluorescence levels. Our results suggest that for comparing expression
levels between strains, the integration locus can be neglected as long as a
sufficient numbers of transformed strains are compared. For expression
optimization of highly expressible proteins, increasing copy number appears to be
the dominant positive influence rather than the integration locus, genomic
rearrangements, deletions, or single-nucleotide polymorphisms (SNPs).IMPORTANCE
Yeasts are commonly used as biotechnological production hosts for proteins and
metabolites. In the yeast Saccharomyces cerevisiae, expression cassettes carrying
foreign genes integrate highly specifically at the targeted sites in the genome.
In contrast, cassettes often integrate at random genomic positions in
nonconventional yeasts, such as Pichia pastoris (syn. Komagataella phaffii).
Hence, cells from the same transformation event often behave differently, with
significant clonal variation necessitating the screening of large numbers of
strains. The importance of this study is that we systematically investigated the
influence of integration events in more than 700 strains. Our findings provide
novel insight into clonal variation in P. pastoris and, thus, how to avoid
pitfalls and obtain reliable results. The underlying mechanisms may also play a
role in other yeasts and hence could be generally relevant for recombinant yeast
protein production strains.
PMID- 29330187
TI - Acquisition of a Novel Sulfur-Oxidizing Symbiont in the Gutless Marine Worm
Inanidrilus exumae.
AB - Gutless phallodrilines are marine annelid worms without a mouth or gut, which
live in an obligate association with multiple bacterial endosymbionts that supply
them with nutrition. In this study, we discovered an unusual symbiont community
in the gutless phallodriline Inanidrilus exumae that differs markedly from the
microbiomes of all 22 of the other host species examined. Comparative 16S rRNA
gene sequence analysis and fluorescence in situ hybridization revealed that I.
exumae harbors cooccurring gamma-, alpha-, and deltaproteobacterial symbionts,
while all other known host species harbor gamma- and either alpha- or
deltaproteobacterial symbionts. Surprisingly, the primary chemoautotrophic sulfur
oxidizer "Candidatus Thiosymbion" that occurs in all other gutless phallodriline
hosts does not appear to be present in I. exumae Instead, I. exumae harbors a
bacterial endosymbiont that resembles "Ca Thiosymbion" morphologically and
metabolically but originates from a novel lineage within the class
Gammaproteobacteria This endosymbiont, named Gamma 4 symbiont here, had a 16S
rRNA gene sequence that differed by at least 7% from those of other free-living
and symbiotic bacteria and by 10% from that of "Ca Thiosymbion." Sulfur globules
in the Gamma 4 symbiont cells, as well as the presence of genes characteristic
for autotrophy (cbbL) and sulfur oxidation (aprA), indicate that this symbiont is
a chemoautotrophic sulfur oxidizer. Our results suggest that a novel lineage of
free-living bacteria was able to establish a stable and specific association with
I. exumae and appears to have displaced the "Ca Thiosymbion" symbionts originally
associated with these hosts.IMPORTANCE All 22 gutless marine phallodriline
species examined to date live in a highly specific association with
endosymbiotic, chemoautotrophic sulfur oxidizers called "Ca Thiosymbion." These
symbionts evolved from a single common ancestor and represent the ancestral trait
for this host group. They are transmitted vertically and assumed to be in
transition to becoming obligate endosymbionts. It is therefore surprising that
despite this ancient, evolutionary relationship between phallodriline hosts and
"Ca Thiosymbion," these symbionts are apparently no longer present in Inanidrilus
exumae They appear to have been displaced by a novel lineage of sulfur-oxidizing
bacteria only very distantly related to "Ca Thiosymbion." Thus, this study
highlights the remarkable plasticity of both animals and bacteria in establishing
beneficial associations: the phallodriline hosts were able to acquire and
maintain symbionts from two very different lineages of bacteria, while sulfur
oxidizing bacteria from two very distantly related lineages were able to
independently establish symbiotic relationships with phallodriline hosts.
PMID- 29330188
TI - Germination, Outgrowth, and Vegetative-Growth Kinetics of Dry-Heat-Treated
Individual Spores of Bacillus Species.
AB - DNA damage kills dry-heated spores of Bacillus subtilis, but dry-heat-treatment
effects on spore germination and outgrowth have not been studied. This is
important, since if dry-heat-killed spores germinate and undergo outgrowth, toxic
proteins could be synthesized. Here, Raman spectroscopy and differential
interference contrast microscopy were used to study germination and outgrowth of
individual dry-heat-treated B. subtilis and Bacillus megaterium spores. The major
findings in this work were as follows: (i) spores dry-heat-treated at 140 degrees
C for 20 min lost nearly all viability but retained their Ca2+-dipicolinic acid
(CaDPA) depot; (ii) in most cases, dry-heat treatment increased the average times
and variability of all major germination events in B. subtilis spore germination
with nutrient germinants or CaDPA, and in one nutrient germination event with B.
megaterium spores; (iii) B. subtilis spore germination with dodecylamine, which
activates the spore CaDPA release channel, was unaffected by dry-heat treatment;
(iv) these results indicate that dry-heat treatment likely damages spore proteins
important in nutrient germinant recognition and cortex peptidoglycan hydrolysis,
but not CaDPA release itself; and (v) analysis of single spores incubated on
nutrient-rich agar showed that while dry-heat-treated spores that are dead can
complete germination, they cannot proceed into outgrowth and thus not to
vegetative growth. The results of this study provide new information on the
effects of dry heat on bacterial spores and indicate that dry-heat sterilization
regimens should produce spores that cannot outgrow and thus cannot synthesize
potentially dangerous proteins.IMPORTANCE Much research has shown that high
temperature dry heat is a promising means for the inactivation of spores on
medical devices and spacecraft decontamination. Dry heat is known to kill
Bacillus subtilis spores by DNA damage. However, knowledge about the effects of
dry-heat treatment on spore germination and outgrowth is limited, especially at
the single spore level. In the current work, Raman spectroscopy and differential
interference contrast microscopy were used to analyze CaDPA levels in and
kinetics of nutrient- and non-nutrient germination of multiple individual dry
heat-treated B. subtilis and Bacillus megaterium spores that were largely dead.
The outgrowth and subsequent cell division of these germinated but dead dry-heat
treated spores were also examined. The knowledge obtained in this study will help
understand the effects of dry heat on spores both on Earth and in space, and
indicates that dry heat can be safely used for sterilization purposes.
PMID- 29330189
TI - Targeted Synthesis and Characterization of a Gene Cluster Encoding NAD(P)H
Dependent 3alpha-, 3beta-, and 12alpha-Hydroxysteroid Dehydrogenases from
Eggerthella CAG:298, a Gut Metagenomic Sequence.
AB - Gut metagenomic sequences provide a rich source of microbial genes, the majority
of which are annotated by homology or unknown. Genes and gene pathways that
encode enzymes catalyzing biotransformation of host bile acids are important to
identify in gut metagenomic sequences due to the importance of bile acids in gut
microbiome structure and host physiology. Hydroxysteroid dehydrogenases (HSDHs)
are pyridine nucleotide-dependent enzymes with stereospecificity and
regiospecificity for bile acid and steroid hydroxyl groups. HSDHs have been
identified in several protein families, including medium-chain and short-chain
dehydrogenase/reductase families as well as the aldo-keto reductase family. These
protein families are large and contain diverse functionalities, making prediction
of HSDH-encoding genes difficult and necessitating biochemical characterization.
We located a gene cluster in Eggerthella sp. CAG:298 predicted to encode three
HSDHs (CDD59473, CDD59474, and CDD59475) and synthesized the genes for
heterologous expression in Escherichia coli We then screened bile acid substrates
against the purified recombinant enzymes. CDD59475 is a novel 12alpha-HSDH, and
we determined that CDD59474 (3alpha-HSDH) and CDD59473 (3beta-HSDH) constitute
novel enzymes in an iso-bile acid pathway. Phylogenetic analysis of these HSDHs
with other gut bacterial HSDHs and closest homologues in the database revealed
predictable clustering of HSDHs by function and identified several likely HSDH
sequences from bacteria isolated or sequenced from diverse mammalian and avian
gut samples.IMPORTANCE Bacterial HSDHs have the potential to significantly alter
the physicochemical properties of bile acids, with implications for
increased/decreased toxicity for gut bacteria and the host. The generation of oxo
bile acids is known to inhibit host enzymes involved in glucocorticoid metabolism
and may alter signaling through nuclear receptors such as farnesoid X receptor
and G-protein-coupled receptor TGR5. Biochemical or similar approaches are
required to fill in many gaps in our ability to link a particular enzymatic
function with a nucleic acid or amino acid sequence. In this regard, we have
identified a novel 12alpha-HSDH and a novel set of genes encoding an iso-bile
acid pathway (3alpha-HSDH and 3beta-HSDH) involved in epimerization and
detoxification of harmful secondary bile acids.
PMID- 29330190
TI - Influence of pig farming on the human's nasal microbiota: The key role of the
airborne microbial communities.
AB - It has been hypothesized that the environment can influence the composition of
the nasal microbiota. However, the direct influence of pig farming on the
anterior and posterior nasal microbiota is unknown. Using a cross-sectional
design, pig farms (n=28) were visited in 2014-2015 and nasal swabs from 43 pig
farmers and 56 pigs as well as 27 air samples taken in the vicinity of pig
enclosure were collected. As controls, nasal swabs from 17 cow farmers and 26 non
animal exposed individuals were also included. Analyses of the microbiota were
performed based on 16S rRNA amplicon sequencing and the DADA2 pipeline to define
sequence variants (SVs). We found that pig farming is strongly associated with
specific microbial signatures (including alpha- and beta-diversity), which are
reflected in the microbiota of the human nose. Furthermore, the microbial
communities were more similar within the same farm as compared to between the
different farms, indicating a specific microbiota pattern for each pig farm. In
total, there were 82 SVs that occurred significantly more abundantly in samples
from pig farms than from cow farmers and non-exposed (i.e. the core pig farm
microbiota). Of those, nine SVs were significantly associated with the posterior
part of the humans' nose. The results strongly indicate that pig farming is
associated with a distinct human nose microbiota. Finally, the community
structures derived by the DADA2 pipeline showed an excellent agreement with the
outputs of the mothur pipeline which was revealed by procrustes
analyses.Importance The knowledge about the influence of animal keeping on the
human microbiome is important. Previous research shows that pets are
significantly affecting the microbial communities of humans. However, the effect
of animal farming on the human microbiome is less clear although it is known that
the air in farms, and in particular pig farms, is charged with high amounts of
dust, bacteria and fungi. In this study we have simultaneously investigated the
nasal microbiota of pigs, humans and the environment in pig farms. We reveal an
enormous impact of pig farming on the human nasal microbiota which is far more
pronounced as compared to cow farming. In addition, we have analyzed the airborne
microbiota and found significant associations suggesting an animal-human
transmission of the microbiota within pig farms. We also reveal that microbial
patterns are farm-specific suggesting that the environment influences animals and
humans in a similar manner.
PMID- 29330192
TI - NHS data show A&E patients waiting longer and big rise in GP flu consultations.
PMID- 29330191
TI - Thermophilic Alkaline Fermentation Followed by Mesophilic Anaerobic Digestion for
Efficient Hydrogen and Methane Production from Waste-Activated Sludge: Dynamics
of Bacterial Pathogens as Revealed by the Combination of Metagenomic and
Quantitative PCR Analyses.
AB - Thermophilic alkaline fermentation followed by mesophilic anaerobic digestion
(TM) for hydrogen and methane production from waste-activated sludge (WAS) was
investigated. The TM process was also compared to a process with mesophilic
alkaline fermentation followed by a mesophilic anaerobic digestion (MM) and one
stage mesophilic anaerobic digestion (M) process. The results showed that both
hydrogen yield (74.5 ml H2/g volatile solids [VS]) and methane yield (150.7 ml
CH4/g VS) in the TM process were higher than those (6.7 ml H2/g VS and 127.8 ml
CH4/g VS, respectively) in the MM process. The lowest methane yield (101.2 ml
CH4/g VS) was obtained with the M process. Taxonomic results obtained from
metagenomic analysis showed that different microbial community compositions were
established in the hydrogen reactors of the TM and MM processes, which also
significantly changed the microbial community compositions in the following
methane reactors compared to that with the M process. The dynamics of bacterial
pathogens were also evaluated. For the TM process, the reduced diversity and
total abundance of bacterial pathogens in WAS were observed in the hydrogen
reactor and were further reduced in the methane reactor, as revealed by
metagenomic analysis. The results also showed not all bacterial pathogens were
reduced in the reactors. For example, Collinsella aerofaciens was enriched in the
hydrogen reactor, which was also confirmed by quantitative PCR (qPCR) analysis.
The study further showed that qPCR was more sensitive for detecting bacterial
pathogens than metagenomic analysis. Although there were some differences in the
relative abundances of bacterial pathogens calculated by metagenomic and qPCR
approaches, both approaches demonstrated that the TM process was more efficient
for the removal of bacterial pathogens than the MM and M processes.IMPORTANCE
This study developed an efficient process for bioenergy (H2 and CH4) production
from WAS and elucidates the dynamics of bacterial pathogens in the process, which
is important for the utilization and safe application of WAS. The study also made
an attempt to combine metagenomic and qPCR analyses to reveal the dynamics of
bacterial pathogens in anaerobic processes, which could overcome the limitations
of each method and provide new insights regarding bacterial pathogens in
environmental samples.
PMID- 29330193
TI - Structure of the human myostatin precursor and determinants of growth factor
latency.
AB - Myostatin, a key regulator of muscle mass in vertebrates, is biosynthesised as a
latent precursor in muscle and is activated by sequential proteolysis of the pro
domain. To investigate the molecular mechanism by which pro-myostatin remains
latent, we have determined the structure of unprocessed pro-myostatin and
analysed the properties of the protein in its different forms. Crystal structures
and SAXS analyses show that pro-myostatin adopts an open, V-shaped structure with
a domain-swapped arrangement. The pro-mature complex, after cleavage of the furin
site, has significantly reduced activity compared with the mature growth factor
and persists as a stable complex that is resistant to the natural antagonist
follistatin. The latency appears to be conferred by a number of distinct features
that collectively stabilise the interaction of the pro-domains with the mature
growth factor, enabling a regulated stepwise activation process, distinct from
the prototypical pro-TGF-beta1. These results provide a basis for understanding
the effect of missense mutations in pro-myostatin and pave the way for the design
of novel myostatin inhibitors.
PMID- 29330194
TI - Telotristat ethyl in carcinoid syndrome: safety and efficacy in the TELECAST
phase 3 trial.
AB - Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well
tolerated in the phase 3 TELESTAR study in patients with carcinoid syndrome (CS)
experiencing >=4 bowel movements per day (BMs/day) while on somatostatin analogs
(SSAs). TELECAST, a phase 3 companion study, assessed the safety and efficacy of
telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea
or elevated urinary 5-hydroxyindoleacetic acid (u5-HIAA)) with <4 BMs/day on SSAs
(or >=1 symptom or >=4 BMs/day if not on SSAs) during a 12-week double-blind
treatment period followed by a 36-week open-label extension (OLE). The primary
safety and efficacy endpoints were incidence of treatment-emergent adverse events
(TEAEs) and percent change from baseline in 24-h u5-HIAA at week 12. Patients (N
= 76) were randomly assigned (1:1:1) to receive placebo or telotristat ethyl 250
mg or 500 mg 3 times per day (tid); 67 continued receiving telotristat ethyl 500
mg tid during the OLE. Through week 12, TEAEs were generally mild to moderate in
severity; 5 (placebo), 1 (telotristat ethyl 250 mg) and 3 (telotristat ethyl 500
mg) patients experienced serious events, and the rate of TEAEs in the OLE was
comparable. At week 12, significant reductions in u5-HIAA from baseline were
observed, with Hodges-Lehmann estimators of median treatment differences from
placebo of -54.0% (95% confidence limits, -85.0%, -25.1%, P < 0.001) and -89.7%
(95% confidence limits, -113.1%, -63.9%, P < 0.001) for telotristat ethyl 250 mg
and 500 mg. These results support the safety and efficacy of telotristat ethyl
when added to SSAs in patients with CS diarrhea (ClinicalTrials.gov identifier:
Nbib2063659).
PMID- 29330195
TI - DICER1 gene mutations in endocrine tumors.
AB - In this review, the importance of the DICER1 gene in the function of endocrine
cells is discussed. There is conclusive evidence that DICER1 mutations play a
crucial role in the development, progression, cell proliferation, therapeutic
responsiveness and behavior of several endocrine tumors. We review the literature
of DICER1 gene mutations in thyroid, parathyroid, pituitary, pineal gland,
endocrine pancreas, paragangliomas, medullary, adrenocortical, ovarian and
testicular tumors. Although significant progress has been made during the last
few years, much more work is needed to fully understand the significance of
DICER1 mutations.
PMID- 29330197
TI - Diplomatic impasse prevents cardiologists from attending conference in Qatar.
PMID- 29330196
TI - Higher prevalence of lymph node metastasis in prostate cancer in patients with
diabetes.
PMID- 29330198
TI - Systematic review of drowning in India: assessment of burden and risk.
AB - AIM: To examine the burden and risk factors for fatal and non-fatal drowning in
India. METHODS: Relevant literature was identified through a systematic search of
19 electronic databases and 19 national and global, institutional, organisational
and government sources of injury data. Search terms used pertained to drowning,
injury, trauma, morbidity and mortality in India. RESULTS: A total of 16 research
articles and five data sources were included in the review. Three national data
sources provided counts of drowning deaths, reporting a range of 1348-62 569
drowning deaths per year. A further three national data sources provided
information on drowning-related morbidity; however, each source presented
different outcome measures making comparison difficult. Ten research studies
investigated risk factors associated with drowning in India. Key risk factors
reported were male gender, young age (0-5 years) and individuals residing in the
North-Eastern part of the country who have high exposure to water sources within
community settings. CONCLUSION: Drowning-related morbidity and mortality have a
significant impact on India, with risk factors identified for this setting
similar to those within other low-income and middle-income countries. Regional
data which look beyond routinely collected data are required to accurately
investigate the burden and impact of drowning, to inform targeted, context
specific approaches for drowning reduction initiatives.
PMID- 29330199
TI - Association between community socioeconomic characteristics and access to youth
flag football.
AB - BACKGROUND: The American Academy of Pediatrics has recommended that opportunities
for non-tackling American football (e.g., flag football) be expanded, given
concerns about the risks of brain trauma from tackle football. This study tested
the hypothesis that flag football would be more accessible in communities
characterised by higher socioeconomic status residents. METHODS: In July 2017,
the locations of community-based organisations offering youth flag and tackle
football for youth between the ages of 6 and 13 in two US states (Georgia and
Washington) were aggregated (n=440). Organisations were coded in terms of the
availability of tackle and/or flag football teams for youth at each year of age
between 6 and 13. Multivariate logistic regression analyses were used to assess
the odds of a community-based football organisation offering flag football, by
community socioeconomic and demographic characteristics. RESULTS: In both states,
communities with more educated residents were more likely to offer flag football
for youth aged 6-12. For example, among 6 year-olds every 10% increase in the
number of adult residents with a college education was associated with 1.51 times
the odds of flag football availability (95% CI 1.22 to 1.86, P<0.001).
CONCLUSION: These results suggest that youth living in communities characterised
by low educational attainment are less likely than other youth to have the option
of a lower contact alternative to tackle football. Relying on voluntary community
level adoption of lower contact alternatives to tackle football may result in
inequitable access to such sport options. This may contribute to an inequitable
burden of brain trauma from youth sport.
PMID- 29330201
TI - CORRECTION.
PMID- 29330200
TI - PWWP-DOMAIN INTERACTOR OF POLYCOMBS1 Interacts with Polycomb-Group Proteins and
Histones and Regulates Arabidopsis Flowering and Development.
AB - Polycomb-group (PcG) proteins mediate epigenetic gene regulation by setting
H3K27me3 via Polycomb Repressive Complex 2 (PRC2). In plants, it is largely
unclear how PcG proteins are recruited to their target genes. Here, we identified
the PWWP-DOMAIN INTERACTOR OF POLYCOMBS1 (PWO1) protein, which interacts with all
three Arabidopsis thaliana PRC2 histone methyltransferases and is required for
maintaining full H3 occupancy at several Arabidopsis genes. PWO1 localizes and
recruits CURLY LEAF to nuclear speckles in Nicotiana benthamiana nuclei,
suggesting a role in spatial organization of PcG regulation. PWO1 belongs to a
gene family with three members having overlapping activities: pwo1 pwo2 pwo3
triple mutants are seedling lethal and show shoot and root meristem arrest, while
pwo1 single mutants are early flowering. Interestingly, the PWWP domain of PWO1
confers binding to histones, which is reduced by a point mutation in a highly
conserved residue of this domain and blocked by phosphorylation of H3S28. PWO1
carrying this mutation is not able to fully complement the pwo1 pwo2 pwo3 triple
mutant, indicating the requirement of this domain for PWO1 in vivo activity.
Thus, the PWO family may present a novel class of histone readers that are
involved in recruiting PcG proteins to subnuclear domains and in promoting
Arabidopsis development.
PMID- 29330202
TI - High-Risk TP53 Mutations Are Associated with Extranodal Extension in Oral Cavity
Squamous Cell Carcinoma.
AB - Purpose: Development of extranodal extension (ENE) has been associated with poor
survival in patients with oral cavity squamous cell carcinoma (OSCC). Here, we
sought to confirm the role of ENE as a poor prognostic factor, and identify
genomic and epigenetic markers of ENE in order to develop a predictive model and
improve treatment selection.Experimental Design: An institutional cohort (The
University of Texas MD Anderson Cancer Center) was utilized to confirm the impact
of ENE on clinical outcomes and evaluate the genomic signature of primary and ENE
containing tissue. OSCC data from The Cancer Genome Atlas (TCGA) were analyzed
for the presence of molecular events associated with nodal and ENE
status.Results: ENE was associated with decreased overall and disease-free
survival. Mutation of the TP53 gene was the most common event in ENE+ OSCC. The
frequency of TP53 mutation in ENE+ tumors was higher compared with ENE- tumors
and wild-type (WT) TP53 was highly represented in pN0 tumors. pN+ENE+ patients
had the highest proportion of high-risk TP53 mutations. Both primary tumors (PT)
and lymph nodes with ENE (LN) exhibited a high rate of TP53 mutations (58.8% and
58.8%, respectively) with no significant change in allele frequency between the
two tissue sites.Conclusions: ENE is one of the most significant markers of OSCC
OS and DFS. There is a shift toward a more aggressive biological phenotype
associated with high-risk mutations of the TP53 gene. Prospective clinical trials
are required to determine whether TP53 mutational status can be used for
personalized treatment decisions. Clin Cancer Res; 24(7); 1727-33. (c)2018 AACR.
PMID- 29330203
TI - Personalized RNA Medicine for Pancreatic Cancer.
AB - Purpose: Since drug responses vary between patients, it is crucial to develop pre
clinical or co-clinical strategies that forecast patient response. In this study,
we tested whether RNA-based therapeutics were suitable for personalized medicine
by using patient-derived-organoid (PDO) and patient-derived-xenograft (PDX)
models.Experimental Design: We performed microRNA (miRNA) profiling of PDX
samples to determine the status of miRNA deregulation in individual pancreatic
ductal adenocarcinoma (PDAC) patients. To deliver personalized RNA-based-therapy
targeting oncogenic miRNAs that form part of this common PDAC miRNA over
expression signature, we packaged antimiR oligonucleotides against one of these
miRNAs in tumor-penetrating nanocomplexes (TPN) targeting cell surface proteins
on PDAC tumors.Results: As a validation for our pre-clinical strategy, the
therapeutic potential of one of our nano-drugs, TPN-21, was first shown to
decrease tumor cell growth and survival in PDO avatars for individual patients,
then in their PDX avatars.Conclusions: This general approach appears suitable for
co-clinical validation of personalized RNA medicine and paves the way to
prospectively identify patients with eligible miRNA profiles for personalized RNA
based therapy. Clin Cancer Res; 24(7); 1734-47. (c)2018 AACR.
PMID- 29330204
TI - Pazopanib Exposure Relationship with Clinical Efficacy and Safety in the Adjuvant
Treatment of Advanced Renal Cell Carcinoma.
AB - Purpose: PROTECT, a phase III, randomized, placebo-controlled study, evaluated
pazopanib efficacy and safety in the adjuvant renal cell carcinoma setting. The
relationship between pazopanib exposure (Ctrough) and efficacy and safety was
evaluated.Patients and Methods: Evaluable steady-state blood trough
concentrations were collected from 311 patients at week 3 or 5 (early Ctrough)
and 250 patients at week 16 or 20 (late Ctrough). Pazopanib pharmacokinetic (PK)
data were analyzed via a population model approach. Relationship between Ctrough
or dose intensity and disease-free survival (DFS) was explored via Kaplan-Meier
and multivariate analysis. Adverse events (AE) and AE-related treatment
discontinuation proportions were summarized by Ctrough quartiles.Results: Most
(>90%) patients with early or late Ctrough data started on 600 mg. Mean early and
late Ctrough overlapped across dose levels. Patients with higher early Ctrough
quartiles achieved longer DFS (adjusted HR, 0.58; 95% confidence interval, 0.42
0.82; P = 0.002). Patients achieving early or late Ctrough >20.5 MUg/mL had
significantly longer DFS: not estimable (NE) versus 29.5 months, P = 0.006, and
NE versus 29.9 months, P = 0.008, respectively. Dose intensity up to week 8 did
not correlate with DFS, consistent with population PK model-based simulations
showing overlapping pazopanib exposure with 600 and 800 mg doses. The proportion
of AE-related treatment discontinuation and grade 3/4 AEs, with the exception of
hypertension, was not correlated to CtroughConclusions: In the adjuvant setting,
higher pazopanib Ctrough was associated with improved DFS and did not increase
treatment discontinuations or grade 3/4 AEs, with the exception of hypertension.
Clin Cancer Res; 24(13); 3005-13. (c)2018 AACRSee related commentary by Rini, p.
2979.
PMID- 29330205
TI - Clinical Utility of a STAT3-Regulated miRNA-200 Family Signature with Prognostic
Potential in Early Gastric Cancer.
AB - Purpose: The majority of gastric cancer patients are diagnosed with late-stage
disease, for which distinct molecular subtypes have been identified that are
potentially amenable to targeted therapies. However, there exists no molecular
classification system with prognostic power for early-stage gastric cancer (EGC)
because the molecular events promoting gastric cancer initiation remain ill
defined.Experimental Design: miRNA microarrays were performed on gastric tissue
from the gp130F/F preclinical EGC mouse model, prior to tumor initiation.
Computation prediction algorithms were performed on multiple data sets and
independent gastric cancer patient cohorts. Quantitative real-time PCR expression
profiling was undertaken in gp130F/F-based mouse strains and human gastric cancer
cells genetically engineered for suppressed activation of the oncogenic latent
transcription factor STAT3. Human gastric cancer cells with modulated expression
of the miR-200 family member miR-429 were also assessed for their proliferative
response.Results: Increased expression of miR-200 family members is associated
with both tumor initiation in a STAT3-dependent manner in gp130F/F mice and EGC
(i.e., stage IA) in patient cohorts. Overexpression of miR-429 also elicited
contrasting pro- and antiproliferative responses in human gastric cancer cells
depending on their cellular histologic subtype. We also identified a miR-200
family-regulated 15-gene signature that integrates multiple key current
indicators of EGC, namely tumor invasion depth, differentiation, histology, and
stage, and provides superior predictive power for overall survival compared with
each EGC indicator alone.Conclusions: Collectively, our discovery of a STAT3
regulated, miR-200 family-associated gene signature specific for EGC, with
predictive power, provides a molecular rationale to classify and stratify EGC
patients for endoscopic treatment. Clin Cancer Res; 24(6); 1459-72. (c)2018 AACR.
PMID- 29330206
TI - Evolution of Cytogenetically Normal Acute Myeloid Leukemia During Therapy and
Relapse: An Exome Sequencing Study of 50 Patients.
AB - Purpose: To study mechanisms of therapy resistance and disease progression, we
analyzed the evolution of cytogenetically normal acute myeloid leukemia (CN-AML)
based on somatic alterations.Experimental Design: We performed exome sequencing
of matched diagnosis, remission, and relapse samples from 50 CN-AML patients
treated with intensive chemotherapy. Mutation patterns were correlated with
clinical parameters.Results: Evolutionary patterns correlated with clinical
outcome. Gain of mutations was associated with late relapse. Alterations of
epigenetic regulators were frequently gained at relapse with recurring
alterations of KDM6A constituting a mechanism of cytarabine resistance. Low KDM6A
expression correlated with adverse clinical outcome, particularly in male
patients. At complete remission, persistent mutations representing preleukemic
lesions were observed in 48% of patients. The persistence of DNMT3A mutations
correlated with shorter time to relapse.Conclusions: Chemotherapy resistance
might be acquired through gain of mutations. Insights into the evolution during
therapy and disease progression lay the foundation for tailored approaches to
treat or prevent relapse of CN-AML. Clin Cancer Res; 24(7); 1716-26. (c)2018
AACR.
PMID- 29330207
TI - Early Assessment of Lung Cancer Immunotherapy Response via Circulating Tumor DNA.
AB - Purpose: Decisions to continue or suspend therapy with immune checkpoint
inhibitors are commonly guided by tumor dynamics seen on serial imaging. However,
immunotherapy responses are uniquely challenging to interpret because tumors
often shrink slowly or can appear transiently enlarged due to inflammation. We
hypothesized that monitoring tumor cell death in real time by quantifying changes
in circulating tumor DNA (ctDNA) levels could enable early assessment of
immunotherapy efficacy.Experimental Design: We compared longitudinal changes in
ctDNA levels with changes in radiographic tumor size and with survival outcomes
in 28 patients with metastatic non-small cell lung cancer (NSCLC) receiving
immune checkpoint inhibitor therapy. CtDNA was quantified by determining the
allele fraction of cancer-associated somatic mutations in plasma using a
multigene next-generation sequencing assay. We defined a ctDNA response as a >50%
decrease in mutant allele fraction from baseline, with a second confirmatory
measurement.Results: Strong agreement was observed between ctDNA response and
radiographic response (Cohen's kappa, 0.753). Median time to initial response
among patients who achieved responses in both categories was 24.5 days by ctDNA
versus 72.5 days by imaging. Time on treatment was significantly longer for ctDNA
responders versus nonresponders (median, 205.5 vs. 69 days; P < 0.001). A ctDNA
response was associated with superior progression-free survival [hazard ratio
(HR), 0.29; 95% CI, 0.09-0.89; P = 0.03], and superior overall survival (HR,
0.17; 95% CI, 0.05-0.62; P = 0.007).Conclusions: A drop in ctDNA level is an
early marker of therapeutic efficacy and predicts prolonged survival in patients
treated with immune checkpoint inhibitors for NSCLC. Clin Cancer Res; 24(8); 1872
80. (c)2018 AACR.
PMID- 29330209
TI - Cognitive Computing to Guide Molecular-Based Therapy Selection: Steps Forward
amid Abundant Need.
PMID- 29330208
TI - Neuroendocrine Tumor Heterogeneity Adds Uncertainty to the World Health
Organization 2010 Classification: Real-World Data from the Spanish Tumor Registry
(R-GETNE).
AB - BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a
complex family of tumors of widely variable clinical behavior. The World Health
Organization (WHO) 2010 classification provided a valuable tool to stratify
neuroendocrine neoplasms (NENs) in three prognostic subgroups based on the
proliferation index. However, substantial heterogeneity remains within these
subgroups, and simplicity sometimes entails an ambiguous and imprecise prognostic
stratification. The purpose of our study was to evaluate the prognostic impact of
histological differentiation within the WHO 2010 grade (G) 1/G2/G3 categories,
and explore additional Ki-67 cutoff values in GEP-NENs. SUBJECTS, MATERIALS, AND
METHODS: A total of 2,813 patients from the Spanish National Tumor Registry
(RGETNE) were analyzed. Cases were classified by histological differentiation as
NETs (neuroendocrine tumors [well differentiated]) or NECs (neuroendocrine
carcinomas [poorly differentiated]), and by Ki-67 index as G1 (Ki-67 <2%), G2 (Ki
67 3%-20%), or G3 (Ki-67 >20%). Patients were stratified into five cohorts: NET
G1, NET-G2, NET-G3, NEC-G2, and NEC-G3. RESULTS: Five-year survival was 72%. Age,
gender, tumor site, grade, differentiation, and stage were all independent
prognostic factors for survival. Further subdivision of the WHO 2010 grading
improved prognostic stratification, both within G2 (5-year survival: 81% [Ki-67
3%-5%], 72% [Ki-67 6%-10%], 52% [Ki-67 11%-20%]) and G3 NENs (5-year survival:
35% [Ki-67 21%-50%], 22% [Ki-67 51%-100%]). Five-year survival was significantly
greater for NET-G2 versus NEC-G2 (75.5% vs. 58.2%) and NET-G3 versus NEC-G3
(43.7% vs. 25.4%). CONCLUSION: Substantial clinical heterogeneity is observed
within G2 and G3 GEP-NENs. The WHO 2010 classification can be improved by
including the additive effect of histological differentiation and the
proliferation index. IMPLICATIONS FOR PRACTICE: Gastroenteropancreatic
neuroendocrine neoplasms are tumors of widely variable clinical behavior, roughly
stratified by the World Health Organization (WHO) 2010 classification into three
subgroups based on proliferation index. Real-world data from 2,813 patients of
the Spanish Registry RGETNE demonstrated substantial clinical heterogeneity
within grade (G) 2 and G3 neuroendocrine neoplasms. Tumor morphology and further
subdivision of grading substantially improves prognostic stratification of these
patients and may help individualize therapy. This combined, additive effect shall
be considered in future classifications of neuroendocrine tumors and incorporated
for stratification purposes in clinical trials.
PMID- 29330210
TI - Trastuzumab Plus Pertuzumab Resistance Does Not Preclude Response to Lapatinib
Plus Trastuzumab in HER2-Amplified Colorectal Cancer.
AB - Human epidermal growth factor 2 (HER2) amplification represents a distinct
molecular subgroup of colorectal cancers that is associated with anti-epidermal
growth factor receptor resistance and sensitivity to dual HER2 targeting.
Although clinical trials have reported activity for trastuzumab/pertuzumab and
trastuzumab/lapatinib combinations, there are no reports on lapatinib plus
trastuzumab activity after resistance to trastuzumab plus pertuzumab. Presented
are three cases of HER2 amplified colorectal cancer that developed acquired
refractoriness to trastuzumab pertuzumab with subsequent clinical benefit to
lapatinib plus trastuzumab, highlighting the potential for HER2 tyrosine kinase
inhibition plus trastuzumab in overcoming trastuzumab/pertuzumab resistance.
PMID- 29330211
TI - Olanzapine-Based Triple Regimens Versus Neurokinin-1 Receptor Antagonist-Based
Triple Regimens in Preventing Chemotherapy-Induced Nausea and Vomiting Associated
with Highly Emetogenic Chemotherapy: A Network Meta-Analysis.
AB - BACKGROUND: The current antiemetic prophylaxis for patients treated with highly
emetogenic chemotherapy (HEC) included the olanzapine-based triplet and
neurokinin-1 receptor antagonists (NK-1RAs)-based triplet. However, which one
shows better antiemetic effect remained unclear. MATERIALS AND METHODS: We
systematically reviewed 43 trials, involving 16,609 patients with HEC, which
compared the following antiemetics at therapeutic dose range for the treatment of
chemotherapy-induced nausea and vomiting: olanzapine, aprepitant, casopitant,
fosaprepitant, netupitant, and rolapitant. The main outcomes were the proportion
of patients who achieved no nausea, complete response (CR), and drug-related
adverse events. A Bayesian network meta-analysis was performed. RESULTS:
Olanzapine-based triple regimens showed significantly better no-nausea rate in
overall phase and delayed phase than aprepitant-based triplet (odds ratios 3.18,
3.00, respectively), casopitant-based triplet (3.78, 4.12, respectively),
fosaprepitant-based triplet (3.08, 4.10, respectively), rolapitant-based triplet
(3.45, 3.20, respectively), and conventional duplex regimens (4.66, 4.38,
respectively). CRs of olanzapine-based triplet were roughly equal to different NK
1RAs-based triplet but better than the conventional duplet. Moreover, no
significant drug-related adverse events were observed in olanzapine-based triple
regimens when compared with NK-1RAs-based triple regimens and duplex regimens.
Additionally, the costs of olanzapine-based regimens were obviously much lower
than the NK-1RA-based regimens. CONCLUSION: Olanzapine-based triplet stood out in
terms of nausea control and drug price but represented no significant difference
of CRs in comparison with NK-1RAs-based triplet. Olanzapine-based triple regimens
should be an optional antiemetic choice for patients with HEC, especially those
suffering from delayed phase nausea. IMPLICATIONS FOR PRACTICE: According to the
results of this study, olanzapine-based triple antiemetic regimens were superior
in both overall and delayed-phase nausea control when compared with various
neurokinin-1 receptor antagonists-based triple regimens in patients with highly
emetogenic chemotherapy (HEC). Olanzapine-based triplet was outstanding in terms
of nausea control and drug price. For cancer patients with HEC, especially those
suffering from delayed-phase nausea, olanzapine-based triple regimens should be
an optional antiemetic choice.
PMID- 29330212
TI - Early and Locally Advanced Metaplastic Breast Cancer: Presentation and Survival
by Receptor Status in Surveillance, Epidemiology, and End Results (SEER) 2010
2014.
AB - BACKGROUND: Metaplastic breast cancer (MBC) is a rare disease subtype
characterized by an aggressive clinical course. MBC is commonly triple negative
(TN), although hormone receptor (HR) positive and human epidermal growth receptor
2 (HER2) positive cases do occur. Previous studies have reported similar outcomes
for MBC with regard to HR status. Less is known about outcomes for HER2 positive
MBC. MATERIALS AND METHODS: Surveillance, Epidemiology, and End Results Program
data were used to identify women diagnosed 2010-2014 with MBC or invasive ductal
carcinoma (IDC). Kaplan-Meier curves estimated overall survival (OS) and
multivariate Cox models were fitted. For survival analyses, only first cancers
were included, and 2014 diagnoses were excluded to allow for sufficient follow
up. RESULTS: Our MBC sample included 1,516 women. Relative to women with IDC,
women with MBC were more likely to be older (63 vs. 61 years), black (16.0% vs.
11.1%), and present with stage III disease (15.6% vs. 10.8%). HER2 positive and
HER2 negative/HR positive MBC tumors represented 5.2% and 23.0% of cases. For MBC
overall, 3-year OS was greatest for women with HER2 positive MBC (91.8%),
relative to women with TN (75.4%) and HER2 negative/HR positive MBC (77.1%). This
difference was more pronounced for stage III MBC, for which 3-year OS was 92.9%,
47.1%, and 42.2% for women with HER2 positive, TN, and HER2 negative/HR positive
MBC, respectively. A multivariate Cox model of MBC demonstrated that HER2
positive tumors (relative to TN) were associated with improved survival (hazard
ratio = 0.32, 95% confidence interval [CI] 0.13-0.79). In a second Cox model of
exclusively HER2 positive tumors, OS did not differ between MBC and IDC disease
subtypes (hazard ratio = 1.16, 95% CI 0.48-2.81). CONCLUSION: In this
contemporary, population-based study of women with MBC, HER2 but not HR status
was associated with improved survival. Survival was similar between HER2 positive
MBC and HER2 positive IDC. This suggests HER2 positive MBC is responsive to HER2
directed therapy, a finding that may offer insights for additional therapeutic
approaches to MBC. IMPLICATIONS FOR PRACTICE: This population-based study reports
recent outcomes, by receptor status, for women with metaplastic breast cancer.
Survival in metaplastic breast cancer is not impacted by hormone receptor status.
To the authors' knowledge, this is the first report indicating that women with
human epidermal growth receptor 2 (HER2) positive metaplastic breast cancer have
survival superior to women with HER2 negative metaplastic breast cancer and
survival similar to women with HER2 positive invasive ductal carcinoma. This
information can be used for counseling patients diagnosed with metaplastic breast
cancer. Further understanding of HER2 positive metaplastic breast cancer could
offer insights for the development of therapeutic approaches to metaplastic
breast cancer more broadly.
PMID- 29330214
TI - Association of Statin Dose With Amputation and Survival in Patients With
Peripheral Artery Disease.
AB - BACKGROUND: Statin dose guidelines for patients with peripheral artery disease
(PAD) are largely based on coronary artery disease and stroke data. The aim of
this study is to determine the effect of statin intensity on PAD outcomes of
amputation and mortality. METHODS: Using an observational cohort study design and
a validated algorithm, we identified patients with incident PAD (2003-2014) in
the national Veterans Affairs data. Highest statin intensity exposure (high
intensity versus low-to-moderate-intensity versus antiplatelet therapy but no
statin use) was determined within 1 year of diagnosis of PAD. Outcomes of
interest were lower extremity amputations and death. The association of statin
intensity with incident amputation and mortality was assessed with Kaplan-Meier
plots, Cox proportional hazards modeling, propensity score-matched analysis, and
sensitivity and subgroup analyses, as well, to reduce confounding. RESULTS: In
155 647 patients with incident PAD, more than a quarter (28%) were not on
statins. Use of high-intensity statins was lowest in patients with PAD only
(6.4%) in comparison with comorbid coronary/carotid disease (18.4%). Incident
amputation and mortality risk declined significantly with any statin use in
comparison with the antiplatelet therapy-only group. In adjusted Cox models, the
high-intensity statin users were associated with lower amputation risk and
mortality in comparison with antiplatelet therapy-only users (hazard ratio, 0.67;
95% confidence interval, 0.61-0.74 and hazard ratio, 0.74; 95% confidence
interval, 0.70-0.77, respectively). Low-to-moderate-intensity statins also had
significant reductions in the risk of amputation and mortality (hazard ratio
amputation, 0.81; 95% confidence interval, 0.75- 0.86; hazard ratio death, 0.83;
95% confidence interval, 0.81-0.86) in comparison with no statins (antiplatelet
therapy only), but effect size was significantly weaker than the high-intensity
statins (P<0.001). The association of high-intensity statins with lower
amputation and death risk remained significant and robust in propensity score
matched, sensitivity, and subgroup analyses. CONCLUSIONS: Statins, especially
high-intensity formulations, are underused in patients with PAD. This is the
first population-based study to show that high-intensity statin use at the time
of PAD diagnosis is associated with a significant reduction in limb loss and
mortality in comparison with low-to-moderate-intensity statin users, and patients
treated only with antiplatelet medications but not with statins, as well.
PMID- 29330215
TI - MicroRNA-195 Regulates Metabolism in Failing Myocardium Via Alterations in
Sirtuin 3 Expression and Mitochondrial Protein Acetylation.
AB - BACKGROUND: Heart failure leads to mitochondrial dysfunction and metabolic
abnormalities of the failing myocardium coupled with an energy-depleted state and
cardiac remodeling. The mitochondrial deacetylase sirtuin 3 (SIRT3) plays a
pivotal role in the maintenance of mitochondrial function through regulating the
mitochondrial acetylome. It is interesting to note that unique cardiac and
systemic microRNAs have been shown to play an important role in cardiac
remodeling by modulating key signaling elements in the myocardium. METHODS:
Cellular signaling was analyzed in human cardiomyocyte-like AC16 cells, and
acetylation levels in rodent models of SIRT3-/-and transgenic microRNA-195 (miR
195) overexpression were compared with wild type. Luciferase assays, Western
blotting, immunoprecipitation assays, and echocardiographic analysis were
performed. Enzymatic activities of pyruvate dehydrogenase (PDH) and ATP synthase
were measured. RESULTS: In failing human myocardium, we observed induction of miR
195 along with decreased expression of the mitochondrial deacetylase SIRT3 that
was associated with increased global protein acetylation. We further investigated
the role of miR-195 in SIRT3-mediated metabolic processes and its impact on
regulating enzymes involved in deacetylation. Proteomic analysis of the total
acetylome showed increased overall acetylation, and specific lysine acetylation
of 2 central mitochondrial metabolic enzymes, PDH and ATP synthase, as well. miR
195 downregulates SIRT3 expression through direct 3'-untranslated region
targeting. Treatments with either sirtuin inhibitor nicotinamide, small
interfering RNA-mediated SIRT3 knockdown or miR-195 overexpression enhanced
acetylation of PDH complex and ATP synthase. This effect diminished PDH and ATP
synthase activity and impaired mitochondrial respiration.SIRT3-/- and miR-195
transgenic mice consistently showed enhanced global protein acetylation,
including PDH complex and ATP synthase, associated with decreased enzymatic
activity. CONCLUSIONS: Altogether, these data suggest that increased levels of
miR-195 in failing myocardium regulate a novel pathway that involves direct SIRT3
suppression and enzymatic inhibition via increased acetylation of PDH and ATP
synthase that are essential for cardiac energy metabolism.
PMID- 29330216
TI - Is placebo response in antidepressant trials rising or not? A reanalysis of
datasets to conclude this long-lasting controversy.
AB - It had long been believed that placebo response rates in antidepressant trials
have been increasing and that they were responsible for rising numbers of so
called failed antidepressant trials. Two recent systematic reviews examined this
issue and reached completely opposite findings. Furukawa and colleagues in a
paper published in 2016 found that the placebo response rates are stable since
1991 and the apparent increase up to 2000 was confounded by changes in trial
design features. By contrast, Khan and colleagues more recently concluded that
placebo response rates had grown steadily in the past 30 years. The two reviews
differed in the datasets they used, definitions of placebo response and
statistical analyses. In this perspective article, we examined if such
differences were responsible for the two reviews' contrasting conclusions. Our
reanalyses confirmed our previous results. We found that in any dataset and for
any placebo response definition, there was no increase in placebo response over
the years when the analysis was adjusted for the confounders related to study
design features or when it was limited to studies published after 1990s. We
conclude that placebo response in antidepressant trials has remained stable for
the past 25 years, during which time the large majority of the studies have come
to share similar design features.
PMID- 29330217
TI - A systematic review of network meta-analyses for pharmacological treatment of
common mental disorders.
AB - QUESTION: Network meta-analyses (NMAs) of treatment efficacy across different
pharmacological treatments help inform clinical decision-making, but their
methodological quality may vary a lot depending also on the quality of the
included primary studies. We therefore conducted a systematic review of NMAs of
pharmacological treatment for common mental disorders in order to assess the
methodological quality of these NMAs, and to relate study characteristics to the
rankings of efficacy and tolerability. STUDY SELECTION AND ANALYSIS: We searched
three databases for NMAs of pharmacological treatment used in major depression,
generalised anxiety disorder (GAD), social anxiety disorder (SAD), post-traumatic
stress disorder (PTSD), obsessive-compulsive disorder (OCD) and specific
phobia.Studies were appraised using the International Society for
Pharmacoeconomics and Outcomes Research checklist of good research practices for
indirect-treatment-comparison and network-meta-analysis studies. FINDINGS: Twenty
NMAs were eligible for inclusion. The number of randomised controlled trials per
NMA ranged from 11 to 234, and included between 801 to more than 26 000
participants. Overall, antidepressants were found to be efficacious and tolerable
agents for several disorders based on rankings (45%) or statistical significance
(55%). The majority of NMAs in this review adhered to guidelines by including a
network diagram (70%), assessing consistency (75%), making use of a random
effects model (75%), providing information on the model used to fit the data
(75%) and adjusting for covariates (75%). CONCLUSIONS: The 20 NMAs of depression
and anxiety disorders, PTSD and/or OCD included in this review demonstrate some
methodological strengths in comparison with the larger body of published NMAs for
medical disorders, support current treatment guidelines and help inform clinical
decision-making.
PMID- 29330218
TI - A Study on Pharmacokinetics of Bosentan with Systems Modeling, Part 1:
Translating Systemic Plasma Concentration to Liver Exposure in Healthy Subjects.
AB - Understanding liver exposure of hepatic transporter substrates in clinical
studies is often critical, as it typically governs pharmacodynamics, drug-drug
interactions, and toxicity for certain drugs. However, this is a challenging task
since there is currently no easy method to directly measure drug concentration in
the human liver. Using bosentan as an example, we demonstrate a new approach to
estimate liver exposure based on observed systemic pharmacokinetics from clinical
studies using physiologically based pharmacokinetic modeling. The prediction was
verified to be both accurate and precise using sensitivity analysis. For
bosentan, the predicted pseudo steady-state unbound liver-to-unbound systemic
plasma concentration ratio was 34.9 (95% confidence interval: 4.2, 50). Drug-drug
interaction (i.e., CYP3A and CYP2B6 induction) and inhibition of hepatic
transporters (i.e., bile salt export pump, multidrug resistance-associated
proteins, and sodium-taurocholate cotransporting polypeptide) were predicted
based on the estimated unbound liver tissue or plasma concentrations. With
further validation and refinement, we conclude that this approach may serve to
predict human liver exposure and complement other methods involving tissue biopsy
and imaging.
PMID- 29330219
TI - A Study on Pharmacokinetics of Bosentan with Systems Modeling, Part 2:
Prospectively Predicting Systemic and Liver Exposure in Healthy Subjects.
AB - Predicting human pharmacokinetics of novel compounds is a critical step in drug
discovery and clinical study design but continues to be a challenging task for
hepatic transporter substrates, particularly in predicting their liver exposures.
In this study, using bosentan as an example, we prospectively predicted systemic
exposure and the (pseudo) steady-state unbound liver-to-unbound plasma ratio
(Kpuu) in healthy subjects using 1) a mechanistic approach solely based on in
vitro hepatocyte assays and 2) an approach based on hepatic process rates from
monkey in vivo data but Michaelis-Menten constants from in vitro data. Both
methods reasonably match the observed human systemic time course data, but the
second method leads to better prediction accuracy. In addition, the second method
can predict a human Kpuu value that is close to the value deduced using clinical
data. We also generated rat and monkey liver Kpuu values in terminal studies.
However, these directly measured animal values are different from the deduced
human value.
PMID- 29330220
TI - Regulation of Drug Metabolism by the Interplay of Inflammatory Signaling,
Steatosis, and Xeno-Sensing Receptors in HepaRG Cells.
AB - Nonalcoholic fatty liver disease (NAFLD), which is characterized by triglyceride
deposition in hepatocytes resulting from imbalanced lipid homeostasis, is of
increasing concern in Western countries, along with progression to nonalcoholic
steatohepatitis (NASH), liver fibrosis, and cirrhosis. Previous studies suggest a
complex, mutual influence of hepatic fat accumulation, NASH-related inflammatory
mediators, and drug-sensing receptors regulating xenobiotic metabolism. Here, we
investigated the suitability of human HepaRG hepatocarcinoma cells as a model for
NAFLD and NASH. Cells were incubated for up to 14 days with an oleate/palmitate
mixture (125 uM each) and/or with 10 ng/ml of the inflammatory mediator
interleukin-6 (IL-6). Effects of these conditions on the regulation of drug
metabolism were studied using xenobiotic agonists of the aryl hydrocarbon
receptor (AHR), pregnane X receptor (PXR), constitutive androstane receptor
(CAR), nuclear factor (erythroid-derived 2)-like 2, and peroxisome proliferator
activated receptor alpha (PPARalpha). Results underpin the suitability of HepaRG
cells for NAFLD- and NASH-related research and constitute a broad-based analysis
of the impact of hepatic fatty acid accumulation and inflammation on drug
metabolism and its inducibility by xenobiotics. IL-6 exerted pronounced negative
regulatory effects on basal as well as on PXR-, CAR-, and PPARalpha-, but not AHR
dependent induction of drug-metabolizing enzymes. This inhibition was related to
diminished transactivation potential of the respective receptors rather than to
reduced transcription of nuclear receptor-encoding mRNAs. The most striking
effects of IL-6 and/or fatty acid treatment were observed in HepaRG cells after
14 days of treatment, making these cultures appear a suitable model for studying
the relationship of fatty acid accumulation, inflammation, and xenobiotic-induced
drug metabolism.
PMID- 29330221
TI - Minimal/measurable residual disease in AML: a consensus document from the
European LeukemiaNet MRD Working Party.
AB - Measurable residual disease (MRD; previously termed minimal residual disease) is
an independent, postdiagnosis, prognostic indicator in acute myeloid leukemia
(AML) that is important for risk stratification and treatment planning, in
conjunction with other well-established clinical, cytogenetic, and molecular data
assessed at diagnosis. MRD can be evaluated using a variety of multiparameter
flow cytometry and molecular protocols, but, to date, these approaches have not
been qualitatively or quantitatively standardized, making their use in clinical
practice challenging. The objective of this work was to identify key clinical and
scientific issues in the measurement and application of MRD in AML, to achieve
consensus on these issues, and to provide guidelines for the current and future
use of MRD in clinical practice. The work was accomplished over 2 years, during 4
meetings by a specially designated MRD Working Party of the European LeukemiaNet.
The group included 24 faculty with expertise in AML hematopathology, molecular
diagnostics, clinical trials, and clinical medicine, from 19 institutions in
Europe and the United States.
PMID- 29330222
TI - Increased sympathovagal imbalance evaluated by heart rate variability is
associated with decreased T2* MRI and left ventricular function in transfusion
dependent thalassemia patients.
AB - Early detection of iron overload cardiomyopathy is an important strategy for
decreasing the mortality rate of patients with transfusion-dependent thalassemia
(TDT). Although cardiac magnetic resonance (CMR) T2* is effective in detecting
cardiac iron deposition, it is costly and not generally available. We
investigated whether heart rate variability (HRV) can be used as a screening
method of iron overload cardiomyopathy in TDT patients. HRV, evaluated by 24-h
Holter monitoring, non-transferrin bound iron (NTBI), serum ferritin, left
ventricular (LV) ejection fraction (LVEF), and CMR-T2* were determined. Patients
with a cardiac iron overload condition had a significantly higher low
frequency/high frequency (LF/HF) ratio than patients without a cardiac iron
overload condition. Log-serum ferritin (r = -0.41, P=0.008), serum NTBI (r =
0.313, P=0.029), and LF/HF ratio (r = -0.286, P=0.043) showed a significant
correlation with CMR-T2*, however only the LF/HF ratio was significantly
correlated with LVEF (r = -0.264, P=0.043). These significant correlations
between HRV and CMR-T2* and LVEF in TDT confirmed the beneficial role of HRV as a
potential early screening tool of cardiac iron overload in thalassemia patients,
especially in a medical center in which CMR T2* is not available. A larger number
of TDT patients with cardiac iron overload are needed to confirm this finding.
PMID- 29330223
TI - The antioxidant xanthorrhizol prevents amyloid-beta-induced oxidative
modification and inactivation of neprilysin.
AB - Activity of neprilysin (NEP), the major protease which cleaves amyloid-beta
peptide (Abeta), is reportedly reduced in the brains of patients with Alzheimer's
disease (AD). Accumulation of Abeta generates reactive oxygen species (ROS) such
as 4-hydroxynonenal (HNE), and then reduces activities of Abeta-degrading enzymes
including NEP. Xanthorrhizol (Xan), a natural sesquiterpenoid, has been reported
to possess antioxidant and anti-inflammatory properties. The present study
examined the effects of Xan on HNE- or oligomeric Abeta42-induced oxidative
modification of NEP protein. Xan was added to the HNE- or oligomeric Abeta42
treated SK-N-SH human neuroblastoma cells and then levels, oxidative modification
and enzymatic activities of NEP protein were measured. Increased HNE levels on
NEP proteins and reduced enzymatic activities of NEP were observed in the HNE- or
oligomeric Abeta42-treated cells. Xan reduced HNE levels on NEP proteins and
preserved enzymatic activities of NEP in HNE- or oligomeric Abeta42-treated
cells. Xan reduced Abeta42 accumulation and protected neurones against oligomeric
Abeta42-induced neurotoxicity through preservation of NEP activities. These
findings indicate that Xan possesses therapeutic potential for the treatment of
neurodegenerative diseases, including AD, and suggest a potential mechanism for
the neuroprotective effects of antioxidants for the prevention of AD.
PMID- 29330224
TI - Vitamin D ameliorates impaired wound healing in streptozotocin-induced diabetic
mice by suppressing NF-kappaB-mediated inflammatory genes.
AB - Diabetic wounds are characterized by delayed wound healing due to persistent
inflammation and excessive production of reactive oxygen species. Vitamin D,
which is well acknowledged to enhance intestinal calcium absorption and increase
in plasma calcium level, has recently been shown to display beneficial effects in
various vascular diseases by promoting angiogenesis and inhibiting inflammatory
responses. However, the role of Vitamin D in diabetic wound healing is still
unclear. In the present study, we investigated the role of Vitamin D in cutaneous
wound healing in streptozotocin (STZ)-induced diabetic mice. Four weeks after
injection of STZ, a full thickness excisional wound was created with a 6-mm
diameter sterile biopsy punch on the dorsum of the mice. Vitamin D was given
consecutively for 14 days by intraperitoneal injection. Vitamin D supplementation
significantly accelerated wound healing in diabetic mice and improved the healing
quality as assessed by measuring the wound closure rate and histomorphometric
analyses. By monitoring the level of pro-inflammatory cytokines tumor necrosis
factor-alpha (TNF-alpha), interleukin (IL) 6 (IL-6), IL-1beta) in the wounds,
reduced inflammatory response was found in VD treatment group. Furthermore,
nuclear factor kappaB (NF-kappaB) pathway was found to be involved in the process
of diabetic wound healing by assessing the relative proteins in diabetic wounds.
Vitamin D supplementation obviously suppressed NF-kappaB pathway activation.
These results demonstrated that Vitamin D improves impaired wound healing in STZ
induced diabetic mice through suppressing NF-kappaB-mediated inflammatory gene
expression.
PMID- 29330225
TI - GENETICS IN ENDOCRINOLOGY: Genetic counseling for congenital hypogonadotropic
hypogonadism and Kallmann syndrome: new challenges in the era of oligogenism and
next-generation sequencing.
AB - Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are
rare, related diseases that prevent normal pubertal development and cause
infertility in affected men and women. However, the infertility carries a good
prognosis as increasing numbers of patients with CHH/KS are now able to have
children through medically assisted procreation. These are genetic diseases that
can be transmitted to patients' offspring. Importantly, patients and their
families should be informed of this risk and given genetic counseling. CHH and KS
are phenotypically and genetically heterogeneous diseases in which the risk of
transmission largely depends on the gene(s) responsible(s). Inheritance may be
classically Mendelian yet more complex; oligogenic modes of transmission have
also been described. The prevalence of oligogenicity has risen dramatically since
the advent of massively parallel next-generation sequencing (NGS) in which tens,
hundreds or thousands of genes are sequenced at the same time. NGS is medically
and economically more efficient and more rapid than traditional Sanger sequencing
and is increasingly being used in medical practice. Thus, it seems plausible that
oligogenic forms of CHH/KS will be increasingly identified making genetic
counseling even more complex. In this context, the main challenge will be to
differentiate true oligogenism from situations when several rare variants that do
not have a clear phenotypic effect are identified by chance. This review aims to
summarize the genetics of CHH/KS and to discuss the challenges of oligogenic
transmission and also its role in incomplete penetrance and variable expressivity
in a perspective of genetic counseling.
PMID- 29330226
TI - Mitotane treatment in patients with metastatic testicular Leydig cell tumor
associated with severe androgen excess.
AB - Mitotane (o,p'DDD) is established in the adjuvant and advanced-stage treatment of
adrenocortical carcinoma and counteracts both tumor growth and tumor-related
steroid production. Both the adrenal glands and the gonads are steroidogenically
active organs and share a common embryogenic origin. Here, we describe the
effects of mitotane in two patients with metastatic Leydig cell tumor (LCT) of
the testes and associated severe androgen excess (serum testosterone 93 and 88
nmol/L, respectively; male reference range 7-27 nmol/L). Both men suffered from
severe restlessness, insomnia and irritability, which they described as
intolerable and disrupting normal life activities. Urinary steroid profiling by
gas chromatography-mass spectrometry (GC-MS) confirmed excess androgen production
and revealed concurrent overproduction of glucocorticoids and glucocorticoid
precursors, which under physiological conditions are produced only by the adrenal
glands but not by the gonads. In a palliative approach, they were commenced on
mitotane, which achieved swift control of the hormone excess and the debilitating
clinical symptoms, restoring normal quality of life. GC-MS demonstrated
normalization of steroid production and decreased 5alpha-reductase activity,
resulting in decreased androgen activation, and imaging demonstrated disease
stabilization for 4-10 months. In conclusion, mitotane can be highly effective in
controlling steroid excess in metastatic LCTs, with anti-tumor activity in some
cases.
PMID- 29330227
TI - Earlier post-operative hypocortisolemia may predict durable remission from
Cushing's disease.
AB - CONTEXT: Achievement of hypocortisolemia following transsphenoidal surgery (TSS)
for Cushing's disease (CD) is associated with successful adenoma resection.
However, up to one-third of these patients recur. OBJECTIVE: We assessed whether
delay in reaching post-operative cortisol nadir may delineate patients at risk of
recurrence for CD following TSS. METHODS: A retrospective review of 257 patients
who received 291 TSS procedures for CD at NIH, between 2003 and 2016. Early
biochemical remission (serum cortisol nadir <5 MUg/dL) was confirmed with
endocrinological and clinical follow-up. Recurrence was detected by laboratory
testing, clinical stigmata or medication dependence during a median follow-up of
11 months. RESULTS: Of the 268 unique admissions, remission was recorded in 241
instances. Recurrence was observed in 9% of these cases with cortisol nadir <=5
MUg/dL and 6% of cases with cortisol nadir <=2 MUg/dL. The timing of
hypocortisolemia was critical in detecting late recurrences. Morning POD-1
cortisol <3.3 MUg/dL was 100% sensitive in predicting durable remission and
morning POD-3 cortisol >=18.5 MUg/dL was 98.6% specific in predicting remote
recurrence. AUROC analysis revealed that hypocortisolemia <=5 ug/dL before 15 h
(post-operative) had 95% sensitivity and an NPV of 0.98 for durable remission.
Serum cortisol level <=2 ug/dL, when achieved before 21 h, improved sensitivity
to 100%. CONCLUSIONS: In our cohort, early, profound hypocortisolemia could be
used as a clinical prediction tool for durable remission. Achievement of
hypocortisolemia <=2 ug/dL before 21 post-operative hours appeared to accurately
predict durable remission in the intermediate term.
PMID- 29330229
TI - Determining the educational impact of the introduction of practice-based small
group learning within an intraprofessional group of doctors.
AB - INTRODUCTION: Practice-Based Small Group Learning (PBSGL) is a system for
continuing professional development introduced into Wessex Region Defence Primary
Healthcare (DPHC) as the Salisbury Plain PBSGL group in 2012. This is a mixed
intraprofessional group comprising general practitioners (GPs), GP trainers,
general practice specialist registrars (GPSTs) and general duties medical
officers (GDMOs). METHODS: An anonymised online questionnaire and thematic
analysis was undertaken to assess the educational impact of PBSGL in such a mixed
role group reflecting military general practice. RESULTS: A positive effect of
PBSGL was demonstrated and further enhanced by the intraprofessional composition.
Positive peer support effects were demonstrated for all members of the cohort
regardless of role. CONCLUSION: PBSGL is an essential pillar for supporting all
doctors working within DPHC. Further qualitative evaluation of cohorts of GDMOs,
GPSTs and mixed-role groups as well as the development of standardised
questionnaires is recommended.
PMID- 29330230
TI - Reducing sedentary behaviour to decrease chronic low back pain: the stand back
randomised trial.
AB - OBJECTIVE: The Stand Back study evaluated the feasibility and effects of a
multicomponent intervention targeting reduced prolonged sitting and pain self
management in desk workers with chronic low back pain (LBP). METHODS: This
randomised controlled trial recruited 27 individuals with chronic LBP, Oswestry
Disability Index (ODI) >10% and desk jobs (sitting >=20 hours/week). Participants
were randomised within strata of ODI (>10%-<20%, >=20%) to receive bimonthly
behavioural counselling (in-person and telephone), a sit-stand desk attachment, a
wrist-worn activity-prompting device and cognitive behavioural therapy for LBP
self-management or control. Self-reported work sitting time, visual analogue
scales (VAS) for LBP and the ODI were assessed by monthly, online questionnaires
and compared across intervention groups using linear mixed models. RESULTS:
Baseline mean (SD) age was 52 (11) years, 78% were women, and ODI was 24.1
(10.5)%. Across the 6-month follow-up in models adjusted for baseline value, work
sitting time was 1.5 hour/day (P<0.001) lower comparing intervention to controls.
Also across follow-up, ODI was on average 8 points lower in intervention versus
control (P=0.001). At 6 months, the relative decrease in ODI from baseline was
50% in intervention and 14% in control (P=0.042). LBP from VAS was not
significantly reduced in intervention versus control, though small-to-moderate
effect sizes favouring the intervention were observed (Cohen's d ranged from 0.22
to 0.42). CONCLUSION: An intervention coupling behavioural counselling targeting
reduced sedentary behaviour and pain self-management is a translatable treatment
strategy that shows promise for treating chronic LBP in desk-bound employees.
TRIAL REGISTRATION NUMBER: NCT0224687; Pre-results.
PMID- 29330231
TI - Some clues for studying long-term health effects of oil spills.
PMID- 29330228
TI - Treatment of aggressive pituitary tumours and carcinomas: results of a European
Society of Endocrinology (ESE) survey 2016.
AB - OBJECTIVE: To collect outcome data in a large cohort of patients with aggressive
pituitary tumours (APT)/carcinomas (PC) and specifically report effects of
temozolomide (TMZ) treatment. DESIGN: Electronic survey to ESE members Dec 2015
Nov 2016. RESULTS: Reports on 166 patients (40 PC, 125 APT, 1 unclassified) were
obtained. Median age at diagnosis was 43 (range 4-79) years. 69% of the tumours
were clinically functioning, and the most frequent immunohistochemical subtype
were corticotroph tumours (45%). Ki-67 index did not distinguish APT from PC,
median 7% and 10% respectively. TMZ was first-line chemotherapy in 157 patients.
At the end of the treatment (median 9 cycles), radiological evaluation showed
complete response (CR) in 6%, partial response (PR) in 31%, stable disease (SD)
in 33% and progressive disease in 30%. Response was more frequent in patients
receiving concomitant radiotherapy and TMZ. CR was seen only in patients with low
MGMT expression. Clinically functioning tumours were more likely to respond than
non-functioning tumours, independent of MGMT status. Of patients with CR, PR and
SD, 25, 40 and 48% respectively progressed after a median of 12-month follow-up.
Other oncological drugs given as primary treatment and to TMZ failures resulted
in PR in 20%. CONCLUSION: This survey confirms that TMZ is established as first
line chemotherapeutic treatment of APT/PC. Clinically functioning tumours, low
MGMT and concurrent radiotherapy were associated with a better response. The
limited long-term effect of TMZ and the poor efficacy of other drugs highlight
the need to identify additional effective therapies.
PMID- 29330232
TI - Interventions Must Be Realistic to Be Useful and Completed in Family Medicine.
AB - Being realistic while helping our patients is this issue's theme. Given the
volume of tasks required in family medicine, recommendations for improvements in
direct care or care measurement cannot just be evidence-based but must also be
realistic. On the list of realistic: ordering antipsychotics for symptoms of
dementia in the elderly, despite recommendations to not do so; ordering
antidepressants without fear that the patient could develop hypertension; mental
health care providers in primary care offices; forced choice for opioid
management; plus agenda setting for visit efficiency. Not yet realistic: trigger
tools to identify adverse events, and pharmacist recommendations related to pain
management before opioid visits. Pneumococcal vaccine compliance is only
realistic if recommendations are not recurrently changed, are paid for, and if
prior immunizations are known. Increasing task delegation to prevent clinician
burnout is not realistic if it burns out the nurses, or if the helpful scribes
cannot be afforded. Helpful, yet questionably realistic: Primary care clinician
involvement for patients in intensive care units and their families, and problem
solving therapy by family physicians. And, let us add 'frightening': few
international medical school graduates to serve the underserved. The most
frequent diagnoses and most critical diagnoses in family medicine are elucidated.
PMID- 29330233
TI - A State Chapter Perspective on Burnout and Resiliency.
PMID- 29330234
TI - Burnout in Young Family Physicians: Variation Across States.
AB - Family physicians 3 years out of training report high rates of emotional
exhaustion and depersonalization, symptoms of burnout, with considerable
variation between states. High rates of burnout among new family physicians is
concerning and significant state-level variation suggests that state-related
factors may contribute to or reduce burnout.
PMID- 29330235
TI - Primary Care Physician Perspectives about Antipsychotics and Other Medications
for Symptoms of Dementia.
AB - BACKGROUND: Guidelines, policies, and warnings have been applied to reduce the
use of medications for behavioral and psychological symptoms of dementia (BPSD).
Because of rare dangerous side effects, antipsychotics have been singled out in
these efforts. However, antipsychotics are still prescribed "off label" to
hundreds of thousands of seniors residing in nursing homes and communities. Our
objective was to evaluate how and why primary-care physicians (PCPs) employ
nonpharmacologic strategies and drugs for BPSD. METHODS: Semi-structured
interviews analyzed via template, immersion and crystallization, and thematic
development of 26 PCPs (16 family practice, 10 general internal medicine) in full
time primary-care practice for at least 3 years in Northwestern Virginia.
RESULTS: PCPs described 4 major themes regarding BPSD management: (1)
nonpharmacologic methods have substantial barriers; (2) medication use is not
constrained by those barriers and is perceived as easy, efficacious, reasonably
safe, and appropriate; (3) pharmacologic policies decrease the use of targeted
medications, including antipsychotics, but also have unintended consequences such
as increased use of alternative risky medications; and (4) PCPs need practical
evidence-based guidelines for all aspects of BPSD management. CONCLUSIONS: PCPs
continue to prescribe medications because they meet patient-oriented goals and
because PCPs perceive drugs, including antipsychotics and their alternatives, to
be more effective and less dangerous than evidence suggests. To optimally treat
BPSD, PCPs need supportive verified prescribing guidelines and access to
nonpharmacologic modalities that are as affordable, available, and efficacious as
drugs; these require and deserve significant additional research and payer
support. Community PCPs should be included in BPSD policy and guideline
development.
PMID- 29330236
TI - Antidepressants and Incident Hypertension in Primary Care Patients.
AB - OBJECTIVE: Many ADMs can alter blood pressure (BP), but the research on the
effect of antidepressant medication (ADMs) on incident hypertension is mixed. We
investigated whether the use of ADMs was associated with the subsequent
development of hypertension. METHODS: A retrospective cohort study was conducted
using electronic medical record data from 6224 patients with primary care visits
from 2008 to 2015. Prescription orders were used to identify ADM use, and
hypertension was defined by medical record diagnosis. Using package insert
warnings, a 3-level ADM exposure variable was created: ADMs that increase BP (ADM
BP+), ADMs that do not increase BP, and no ADM. Unadjusted and adjusted Cox
proportional hazard models were computed to estimate the association between the
ADM exposure and incident hypertension. RESULTS: Unadjusted results revealed that
ADM BP+ use compared with the no ADM group was significantly associated with
incident hypertension (hazard ratio, 1.30; 95% confidence interval, 1.08-1.57).
After adjusting for covariates, ADM BP+ use was no longer significantly
associated with incident hypertension (hazard ratio, 1.20; 95% confidence
interval, 0.97-1.49). CONCLUSIONS: Commonly used ADMs were not associated with
incident hypertension after controlling for other factors associated with ADM use
and hypertension. Research on potential dose and duration effects is warranted.
PMID- 29330237
TI - 'The Hand on the Doorknob': Visit Agenda Setting by Complex Patients and Their
Primary Care Physicians.
AB - BACKGROUND: Choosing which issues to discuss in the limited time available during
primary care visits is an important task for complex patients with chronic
conditions. DESIGN, SETTING, AND PARTICIPANTS: We conducted sequential interviews
with complex patients (n = 40) and their primary care physicians (n = 17) from 3
different health systems to investigate how patients and physicians prepare for
visits, how visit agendas are determined, and how discussion priorities are
established during time-limited visits. KEY RESULTS: Visit flow and alignment
were enhanced when both patients and physicians were effectively prepared before
the visit, when the patient brought up highest-priority items first, the
physician and patient worked together at the beginning of the visit to establish
the visit agenda, and other team members contributed to agenda setting. A range
of factors were identified that undermined the ability of patient and physicians
to establish an efficient working agenda: the most prominent were time pressure
and short visit lengths, but also included differing visit expectations, patient
hesitancy to bring up embarrassing concerns, electronic medical
record/documentation requirements, differences balancing current symptoms versus
future medical risk, nonactionable items, differing philosophies about
medications and lifestyle interventions, and difficulty by patients in
prioritizing their top concerns. CONCLUSIONS: Primary care patients and their
physicians adopt a range of different strategies to address the time constraints
during visits. The primary factor that supported well-aligned visits was the
ability for patients and physicians to proactively negotiate the visit agenda at
the beginning of the visit. Efforts to optimize care within time-constrained
systems should focus on helping patients more effectively prepare for visits.
Physicians should ask for the patient's agenda early, explain visit parameters,
establish a reasonable number of concerns that can be discussed, and collaborate
on a plan to deal with concerns that cannot be addressed during the visit.
PMID- 29330238
TI - Changing Patterns of Mental Health Care Use: The Role of Integrated Mental Health
Services in Veteran Affairs Primary Care.
AB - OBJECTIVE: Aiming to foster timely, high-quality mental health care for Veterans,
VA's Primary Care-Mental Health Integration (PC-MHI) embeds mental health
specialists in primary care and promotes care management for depression. PC-MHI
and patient-centered medical home providers work together to provide the bulk of
mental health care for primary care patients with low-to-moderate-complexity
mental health conditions. This study examines whether increasing primary care
clinic engagement in PC-MHI services is associated with changes in patient health
care utilization and costs. METHODS: We performed a retrospective longitudinal
cohort study of primary care patients with identified mental health needs in 29
Southern California VA clinics from October 1, 2008 to September 30, 2013, using
electronic administrative data (n = 66,638). We calculated clinic PC-MHI
engagement as the proportion of patients receiving PC-MHI services among all
primary care clinic patients in each year. Capitalizing on variation in PC-MHI
engagement across clinics, our multivariable regression models predicted annual
patient use of 1) non-primary care based mental health specialty (MHS) visits, 2)
total mental health visits (ie, the sum of MHS and PC-MHI visits), and 3) health
care utilization and costs. We controlled for year- and clinic-fixed effects,
other clinic interventions, and patient characteristics. RESULTS: Median clinic
PC-MHI engagement increased by 8.2 percentage points over 5 years. At any given
year, patients treated at a clinic with 1 percentage-point higher PC-MHI
engagement was associated with 0.5% more total mental health visits (CI, 0.18% to
0.90%; P = .003) and 1.0% fewer MHS visits (CI, -1.6% to -0.3%; P = .002); this
is a substitution rate, at the mean, of 1.5 PC-MHI visits for each MHS visit.
There was no PC-MHI effect on other health care utilization and costs.
CONCLUSIONS: As intended, greater clinic engagement in PC-MHI services seems to
increase realized accessibility to mental health care for primary care patients,
substituting PC-MHI for MHS visits, without increasing acute care use or total
costs. Thus, PC-MHI services within primary care clinics may improve mental
health care value at the patient population level. More research is needed to
understand the relationship between clinic PC-MHI engagement and clinical quality
of mental health care.
PMID- 29330239
TI - One Year of Family Physicians' Observations on Working with Medical Scribes.
AB - PURPOSE: The immense clerical burden felt by physicians is one of the leading
causes of burnout. Scribes are increasingly being used to help alleviate this
burden, yet few published studies investigate how scribes affect physicians'
daily work, attitudes and behaviors, and relationships with patients and the
workplace. METHODS: Using a longitudinal observational design, data were
collected, over 1 year, from 4 physicians working with 2 scribes at a single
academic family medicine practice. Physician experience was measured by open
ended written reflections requested after each 4-hour clinic session. A data
driven codebook was generated using a constant comparative method with grounded
theory approach. RESULTS: A total of 361 physician reflections were completed,
yielding 150 distinct excerpts; 289 codes were assigned. The 11 themes that
emerged were further categorized under 4 domains. The most frequently recurring
domain was clinic operations, which comprised 51.6% of the codes. Joy of
practice, quality of care, and patient experience comprised 22.1%, 16.3%, and
10.0% of the codes, respectively. CONCLUSIONS: Our study suggests that
integrating scribes into a primary care clinic can produce positive outcomes that
go beyond reducing clerical burden for physicians. Scribes may benefit patient
experience, quality of care, clinic operations, and joy of practice.
PMID- 29330240
TI - Structured Management of Chronic Nonmalignant Pain with Opioids in a Rural
Primary Care Office.
AB - INTRODUCTION: The use of opioid medication for nonmalignant chronic pain (NMCP)
increased dramatically during the last 20 years. There have been regulatory
changes implemented to reduce the risk of harm to both patients and society. Much
of the burden of monitoring these patients is falling on primary care physicians
(PCPs), who do not have the time or resources to handle what is entailed in a
best-practice approach to NMCP. METHODS: A retrospective study was conducted with
all patients on opioid medication for NMCP who were enrolled onto an individual
PCP's practice. All were required to engage with a new care system. Patients had
the option to remain on opioids, to wean opioids, or to transfer care. Patients
who remained in the practice on opioids were required to have an office visit on
a day dedicated solely to NMCP every 3 months. Each visit involved verifying the
controlled substance contract, a urine drug screen, board of pharmacy monitoring,
pain-targeted history and physical, calculation of the average morphine
equivalents used, and evaluations of pain, functional status, and mood.
Characteristics more likely to lead to weaning from opioids were monitored, as
was the program effect on the patients remaining on opioids. RESULTS: With this
practice model, 32 patients treated with opioids for NMCP were enrolled. Of
these, 38% (n = 12) elected to wean opioids, 53% (n = 17) continued opioid
medication, and 9% (n = 3) transferred care. Mean morphine equivalent mg/day was
the prime determinant for ability to wean (17.01 mg/day) compared with
maintaining (30.61 mg/day) (P = .0397; CI, 0.68 to 26.51). Patients maintaining
opioid treatment showed no statistically significant change in any measured data
point from beginning until end of the evaluation period. CONCLUSION: Given the
choice of following a specific structured care system of opioid medication
management or leaving the practice, most patients agreed to the structured
system. This approach provided a high degree of compliance with controlled
substance regulations and is associated with a reduced number of opioid
prescriptions. Patients who were on lower doses of opioid medication are more
likely to wean their use with this model.
PMID- 29330241
TI - Primary Care Physician Involvement in Shared Decision Making for Critically Ill
Patients and Family Satisfaction with Care.
AB - PURPOSE: An intensive care unit (ICU) patient's primary care physician (PCP) may
be able to assist family with certain ICU shared medical decisions. We explored
whether families of patients in nonopen ICUs who nevertheless report involvement
of a patient's PCP in medical decision making are more satisfied with ICU shared
decision making than families who do not. METHODS: Between March 2013 and
December 2015, we administered the Family Satisfaction in the ICU 24 survey to
family members of adult neuroscience ICU patients. We compared the mean score for
the survey subsection regarding shared decision making (graded on a 100-point
scale), as well as individual survey items, between those who reported the
patient's PCP involvement in any medical decision making versus those who did
not. RESULTS: Among 263 respondents, there was no difference in mean overall
decision-making satisfaction scores for those who reported involvement (81.1; SD
= 15.2) versus those who did not (80.1; SD = 12.8; P = .16). However, a higher
proportion reporting involvement felt completely satisfied with their 1)
inclusion in the ICU decision making process (75.9% vs 61.4%; P = .055), and 2)
control over the care of the patient (73.6% vs 55.6%; P = .02), with no
difference regarding consistency of clinical information provided by the medical
team (64.8% vs 63.5%; P = 1.00). CONCLUSIONS: Families who report involvement of
a patient's PCP in medical decision making for critically ill patients may be
more satisfied than those who do not with regard to specific aspects of ICU
decision making. Further research would help understand how best to engage PCPs
in shared decisions.
PMID- 29330242
TI - Patient Perspectives on Discussions of Electronic Cigarettes in Primary Care.
AB - PURPOSE: Patient preferences regarding the role of the primary care provider
(PCP) in discussing electronic cigarette (e-cigarette) use are unknown. METHODS:
We administered a cross-sectional survey to 568 adult patients in a family
medicine clinic to explore e-cigarette use, sources of information on e
cigarettes, perceived knowledge about e-cigarette health effects, views regarding
PCP knowledge of e-cigarettes, interest in discussing e-cigarettes with PCPs and
preferred format for e-cigarette information. We performed chi2 testing with a 2
tailed P < .05 to assess associations between e-cigarette use and these measures.
RESULTS: The prevalence of e-cigarette use was 10% for recent (<=30 days) use and
29% for nonrecent (>30 days) use. Prevalence was significantly higher among those
who were younger, less educated, or smoked cigarettes, but did not vary by sex or
self-reported health status. Roughly one quarter of participants believed they
were knowledgeable about the health effects of e-cigarettes, secondhand smoke,
and quitting cigarettes. Sources of e-cigarette information included television
advertisements (56.6%), friends and family (49.9%), or e-cigarette shops (25.5%),
but included physician offices much less frequently (6.0%). Although 30.2%
disagreed that their PCP knew a lot about e-cigarettes, 62.0% were comfortable
discussing e-cigarettes with their PCP. However, only 25% of all patients wanted
their PCP to discuss e-cigarettes with them, but 62.0% of recent e-cigarette
users wanted such a discussion. Most preferred a brief discussion or handout to a
lengthy discussion. CONCLUSION: PCPs were infrequent sources of information for
patients regarding e-cigarette use. PCPs need evidence-based strategies to help
them address e-cigarettes in primary care.
PMID- 29330243
TI - Task Delegation and Burnout Trade-offs Among Primary Care Providers and Nurses in
Veterans Affairs Patient Aligned Care Teams (VA PACTs).
AB - PURPOSE: Appropriate delegation of clinical tasks from primary care providers
(PCPs) to other team members may reduce employee burnout in primary care.
However, (1) the extent to which delegation occurs within multidisciplinary
teams, (2) factors associated with greater delegation, and (3) whether delegation
is associated with burnout are all unknown. METHODS: We performed a national
cross-sectional survey of Veterans Affairs (VA) PCP-nurse dyads in Department of
VA primary care clinics, 4 years into the VA's patient-centered medical home
initiative. PCPs reported the extent to which they relied on other team members
to complete 15 common primary care tasks; paired nurses reported how much they
were relied on to complete the same tasks. A composite score of task
delegation/reliance was developed by taking the average of the responses to the
15 questions. We performed multivariable regression to explore predictors of task
delegation and burnout. RESULTS: Among 777 PCP-nurse dyads, PCPs reported
delegating tasks less than nurses reported being relied on (PCP mean +/- standard
deviation composite delegation score, 2.97+/- 0.64 [range, 1-4]; nurse composite
reliance score, 3.26 +/- 0.50 [range, 1-4]). Approximately 48% of PCPs and 35% of
nurses reported burnout. PCPs who reported more task delegation reported less
burnout (odds ratio [OR], 0.62 per unit of delegation; 95% confidence interval
[CI], 0.49-0.78), whereas nurses who reported being relied on more reported more
burnout (OR, 1.83 per unit of reliance; 95% CI, 1.33-2.5). CONCLUSIONS: Task
delegation was associated with less burnout for PCPs, whereas task reliance was
associated with greater burnout for nurses. Strategies to improve work life in
primary care by increasing PCP task delegation must consider the impact on
nurses.
PMID- 29330245
TI - Impact of Pharmacist Previsit Input to Providers on Chronic Opioid Prescribing
Safety.
AB - INTRODUCTION: Primary care providers (PCPs) account for half of opioid
prescriptions, often feel chronic pain patients are challenging to manage, and
there is wide variability in practice patterns. The purpose of this pilot study
was to evaluate the impact of a previsit pharmacist review of high-risk patients
treated with opioids for chronic pain on compliance to guideline recommendations
at a family medicine residency clinic. METHODS: All adult patients with an
appointment for chronic pain who were prescribed >50 morphine milligram
equivalents (MMEs)/day had charts reviewed by a pharmacist before each
appointment; recommendations were sent electronically to the provider before the
appointment. After 4 months of implementation, each patient's chart was manually
reviewed to gather outcome variables. The primary outcomes were the mean MMEs/day
and pain scores. RESULTS: Pharmacist previsit recommendations were provided for
45 patients. When comparing outcomes before and after intervention, the mean
MMEs/day decreased by 14% (P < .001), with no change in pain scores (P = .783).
Statistically significant improvements were noted in multiple other secondary
opioid safety outcomes. CONCLUSION: Clinical pharmacists providing previsit
recommendations was associated with decreased opioid utilization with no
corresponding increase in pain scores and increased compliance to guideline
recommendations.
PMID- 29330244
TI - Primary Care Physicians' Struggle with Current Adult Pneumococcal Vaccine
Recommendations.
AB - INTRODUCTION: In 2012, the Advisory Committee on Immunization Practices
recommended 13-valent pneumococcal conjugate vaccine (PCV13) in series with 23
valent pneumococcal polysaccharide vaccine (PPSV23) for at-risk adults >=19; in
2014, it expanded this recommendation to adults >=65. Primary care physicians'
practice, knowledge, attitudes, and beliefs regarding these recommendations are
unknown. METHODS: Primary care physicians throughout the U.S. were surveyed by E
mail and post from December 2015 to January 2016. RESULTS: Response rate was 66%
(617 of 935). Over 95% of respondents reported routinely assessing adults'
vaccination status and recommending both vaccines. A majority found the current
recommendations to be clear (50% "very clear," 38% "somewhat clear"). Twenty
percent found the upfront cost of purchasing PCV13, lack of insurance coverage,
inadequate reimbursement, and difficulty determining vaccination history to be
"major barriers" to giving these vaccines. Knowledge of recommendations varied,
with 83% identifying the PCV13 recommendation for adults >=65 and only 21%
identifying the recommended interval between PCV13 and PPSV23 in an individual
<65 at increased risk. CONCLUSIONS: Almost all surveyed physicians reported
recommending both pneumococcal vaccines, but a disconnect seems to exist between
perceived clarity and knowledge of the recommendations. Optimal implementation of
these recommendations will require addressing knowledge gaps and reported
barriers.
PMID- 29330246
TI - The Accuracy of Trigger Tools to Detect Preventable Adverse Events in Primary
Care: A Systematic Review.
AB - PURPOSE: To understand the ability of trigger tools to detect preventable adverse
events (pAEs) in the primary care outpatient setting using the Institute for
Healthcare Improvement's (IHI) Outpatient Adverse Event Trigger Tool (IHI Tool).
METHODS: The OVID MEDLINE and OVID MEDLINE In-process and non-Indexed citations
databases were queried using controlled vocabulary and Medical Subject Headings
related to the concepts "primary care" and "adverse events." Included articles
were conducted in the outpatient setting, used at least 1 of the triggers
identified in the IHI Tool, and identified pAEs of any type. Articles were
selected for inclusion based first on assessment of titles then abstracts by 2
trained reviewers independently, followed by full text review by 2 authors.
RESULTS: Our search identified 6435 unique articles, and we included 15 in our
review. The most common studied trigger was laboratory abnormalities. The most
common pAEs were medication errors followed by unplanned hospitalizations. The
effectiveness of triggers in identifying AEs varied widely. CONCLUSION: There is
insufficient data on the IHI Tool and its use to identify pAEs in the general
real-world outpatient setting. Health care providers of the primary care setting
may benefit from better trigger tools and other methods to help them detect pAEs.
More research is needed to further evaluate the effectiveness of trigger tools to
reduce barriers of cost and time and improve patient safety.
PMID- 29330247
TI - Frequency and Criticality of Diagnoses in Family Medicine Practices: From the
National Ambulatory Medical Care Survey (NAMCS).
AB - BACKGROUND: Family medicine is a specialty of breadth, providing comprehensive
health care for the individual and the family that integrates the broad scope of
clinical, social, and behavioral sciences. As such, the scope of practice (SOP)
for family medicine is extensive; however, over time many family physicians
narrow their SOP. We sought to provide a nationally representative description of
the most common and the most critical diagnoses that family physicians see in
their practice. METHODS: Data were extracted from the 2012 National Ambulatory
Medical Care Survey (NAMCS) to select all ICD-9 codes reported by family
physicians. A panel of family physicians then reviewed 1893 ICD-9 codes to place
each code into an American Board of Family Medicine Family Medicine Certification
Examination test plan specifications (TPS) category and provide a rating for an
Index of Harm (IoH). RESULTS: An analysis of all 1893 ICD-9 codes seen by family
physicians in the 2012 NAMCS found that 198 ICD-9 codes could not be assigned a
TPS category, leaving 1695 ICD-9 codes in the dataset. Top 10 lists of ICD-9
codes by TPS category were created for both frequency and IoH. CONCLUSIONS: This
study provides a nationally representative description of the most common
diagnoses that family physicians are seeing in their practice and the criticality
of these diagnoses. These results provide insight into the domain of the
specialty of family medicine. Medical educators may use these results to better
tailor education and training to practice.
PMID- 29330248
TI - The Effectiveness of Problem-Solving Therapy for Primary Care Patients'
Depressive and/or Anxiety Disorders: A Systematic Review and Meta-Analysis.
AB - BACKGROUND: There is increasing demand for managing depressive and/or anxiety
disorders among primary care patients. Problem-solving therapy (PST) is a brief
evidence- and strength-based psychotherapy that has received increasing support
for its effectiveness in managing depression and anxiety among primary care
patients. METHODS: We conducted a systematic review and meta-analysis of clinical
trials examining PST for patients with depression and/or anxiety in primary care
as identified by searches for published literature across 6 databases and manual
searching. A weighted average of treatment effect size estimates per study was
used for meta-analysis and moderator analysis. RESULTS: From an initial pool of
153 primary studies, 11 studies (with 2072 participants) met inclusion criteria
for synthesis. PST reported an overall significant treatment effect for primary
care depression and/or anxiety (d = 0.673; P < .001). Participants' age and sex
moderated treatment effects. Physician-involved PST in primary care, despite a
significantly smaller treatment effect size than mental health provider only PST,
reported an overall statistically significant effect (d = 0.35; P = .029).
CONCLUSIONS: Results from the study supported PST's effectiveness for primary
care depression and/or anxiety. Our preliminary results also indicated that
physician-involved PST offers meaningful improvements for primary care patients'
depression and/or anxiety.
PMID- 29330249
TI - Is It Idiopathic Pulmonary Fibrosis or Not?
AB - Pulmonary fibrosis is not uncommon. Usual interstitial pneumonitis
(UIP)/idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic
pulmonary fibrotic diseases and has the worst prognosis with a mean life
expectancy of 3.8 years. The American Thoracic Society has provided guidelines
for the accurate diagnosis of IPF.In 2014, 2 antifibrotic medications were
approved in the United States that target the multiple fibrotic pathways of UIP,
which increased the need for early and accurate diagnosis of IPF. The early and
correct diagnosis is hampered by mimickers that include nonspecific interstitial
pneumonitis, chronic hypersensitivity pneumonitis, and fibrotic sarcoidosis.
Careful history taking, serologic testing, and Computer Tomography (CT)
inspection can frequently make the correct diagnosis without need of invasive
procedure. The purpose of this article is to share the most important aspects of
the clinical and radiology presentation of IPF and its mimickers to enhance
primary care clinician's ability to correctly and noninvasively diagnose UIP/IPF.
PMID- 29330250
TI - The Intersection of National Immigration and Healthcare Policy.
AB - Immigration policy and health care policy remain principal undertakings of the
federal government. The two have recently been pursued independently in the
judicial and legislative arenas. Unbeknownst to many policymakers, however,
national immigration policy and health care policy are linked in ways that, if
unattended, could undermine the well-being of a significant portion of the US
population, specifically medically underserved rural and urban populations. Using
current data from a workforce report of the Association of American Colleges and
the published literature, we demonstrate the significant impact that contemporary
immigration policy directives may have on the number and distribution of
international medical graduates who currently provide-and by the year 2025 will
provide-a significant portion of primary health care in the United States,
especially in underserved small urban and rural communities.
PMID- 29330251
TI - Diplomate Status: A Matter of Distinction.
PMID- 29330252
TI - The Numbers Quandary in Family Medicine Obstetrics.
PMID- 29330253
TI - Re: The Numbers Quandary in Family Medicine Obstetrics.
PMID- 29330254
TI - Increased Levels of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 in
Ischemic Stroke and Transient Ischemic Attack.
AB - BACKGROUND: Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX
1) has been shown to be increased in patients with acute ischemic stroke. Here,
we evaluated plasma sLOX-1 levels and vascular carotid plaque LOX-1 (ie, OLR1)
gene expression in patients with ischemic stroke and transient ischemic attack
(TIA) with particular focus on their relation to time since symptom onset.
METHODS AND RESULTS: Plasma sLOX-1 (n=232) and carotid plaque OLR1 gene
expression (n=146) were evaluated in patients who were referred to evaluation for
carotid endarterectomy, as well as in healthy control plasma (n=81). Patients
were categorized according to presence of acute ischemic stroke or transient
ischemic attack (n=35) <=7 days, >7 days <=3 months (n=90), >3 months (n=40), or
no reported symptoms before study inclusion (n=67). Our major findings were the
following: (1) Patients with carotid atherosclerosis had increased plasma sLOX-1
levels as compared with controls. (2) Plaque OLR1 mRNA levels were increased in
carotid plaques (n=146) compared with nonatherosclerotic vessels (ie, common
iliac arteries of organ donors, n=10). (3) There were no differences in sLOX
plasma levels or OLR1 gene expression when analyzed according to the time since
relevant cerebral ischemic symptoms. (4) Also patients with severe carotid
atherosclerosis without any previous ischemic events had raised sLOX-1 levels.
(5) Immunostaining showed colocalization between LOX-1 and macrophages within the
carotid plaques. (6) Also patients with acute stroke (within 7 days) caused by
atrial fibrillation (n=22) had comparable raised sLOX-1 levels. CONCLUSIONS: sLOX
1 levels are elevated in patients with ischemic stroke and transient ischemic
attack independent of cause and time since the ischemic event.
PMID- 29330255
TI - High-Intensity Cigarette Smoking Is Associated With Incident Diabetes Mellitus In
Black Adults: The Jackson Heart Study.
AB - BACKGROUND: Previous reports on whether smoking is associated with insulin
resistance and diabetes mellitus have yielded inconsistent findings. We aimed to
evaluate the relationship between cigarette smoking and incident diabetes
mellitus in the Jackson Heart Study. METHODS AND RESULTS: Jackson Heart Study
participants enrolled at baseline without prevalent diabetes mellitus (n=2991)
were classified by self-report as current smokers, past smokers (smoked >=400
cigarettes/life and no longer smoking), or never smokers. We quantified smoking
intensity by number of cigarettes smoked daily; we considered >=20 cigarettes per
day (1 pack) "high-intensity." We defined diabetes mellitus as fasting glucose
>=126 mg/dL, hemoglobin A1c >=6.5% or International Federation of Clinical
Chemistry units HbA1c 48 mmol/mol, or use of diabetes mellitus medication. We
estimated the adjusted associations of smoking status, intensity, and dose (pack
years) with incident diabetes mellitus using Poisson regression models. At
baseline there were 361 baseline current (1-10 cigarettes per day [n=242]; >=20
[n=119]), 502 past, and 2128 never smokers. From Visit 1 to Visit 3 (mean 8.0+/
0.9 years), 479 participants developed incident diabetes mellitus. After
adjustment for covariates, baseline current smokers who smoked less than a pack/d
and past smokers had similar rates of incident diabetes mellitus compared with
never smokers (incidence rate ratios 1.04, 95% confidence interval, 0.69-1.58 and
1.08, 95% confidence interval, 0.82-1.42, respectively). Baseline current high
intensity smokers had a 79% (95% confidence interval, 1.14-2.81) higher incidence
of diabetes mellitus compared with never smokers. Smoking dose (per 10 pack
years) was also associated with a higher incidence of diabetes mellitus
(incidence rate ratios 1.10, 95% confidence interval, 1.03-1.19) in adjusted
models. CONCLUSIONS: High-intensity cigarette smoking and smoking pack-years are
associated with an increased risk of developing diabetes mellitus in blacks.
PMID- 29330256
TI - Osteoprotegerin Is Associated With Major Bleeding But Not With Cardiovascular
Outcomes in Patients With Acute Coronary Syndromes: Insights From the PLATO
(Platelet Inhibition and Patient Outcomes) Trial.
AB - BACKGROUND: Elevated levels of osteoprotegerin, a secreted tumor necrosis factor
related molecule, might be associated with adverse outcomes in patients with
coronary artery disease. We measured plasma osteoprotegerin concentrations on
hospital admission, at discharge, and at 1 and 6 months after discharge in a
predefined subset (n=5135) of patients with acute coronary syndromes in the PLATO
(Platelet Inhibition and Patient Outcomes) trial. METHODS AND RESULTS: The
associations between osteoprotegerin and the composite end point of
cardiovascular death, nonprocedural spontaneous myocardial infarction or stroke,
and non-coronary artery bypass grafting major bleeding during 1 year of follow-up
were assessed by Cox proportional hazards models. Event rates of the composite
end point per increasing quartile groups at baseline were 5.2%, 7.5%, 9.2%, and
11.9%. A 50% increase in osteoprotegerin level was associated with a hazard ratio
(HR) of 1.31 (95% confidence interval [CI], 1.21-1.42) for the composite end
point but was not significant in adjusted analysis (ie, clinical characteristics
and levels of C-reactive protein, troponin T, NT-proBNP [N-terminal pro-B-type
natriuretic peptide], and growth differentiation factor-15). The corresponding
rates of non-coronary artery bypass grafting major bleeding were 2.4%, 2.2%,
3.8%, and 7.2%, with an unadjusted HR of 1.52 (95% CI, 1.36-1.69), and a fully
adjusted HR of 1.26 (95% CI, 1.09-1.46). The multivariable association between
the osteoprotegerin concentrations and the primary end point after 1 month
resulted in an HR of 1.09 (95% CI, 0.89-1.33); for major bleeding after 1 month,
the HR was 1.33 (95% CI, 0.91-1.96). CONCLUSIONS: In patients with acute coronary
syndrome treated with dual antiplatelet therapy, osteoprotegerin was an
independent marker of major bleeding but not of ischemic cardiovascular events.
Thus, high osteoprotegerin levels may be useful in increasing awareness of
increased bleeding risk in patients with acute coronary syndrome receiving
antithrombotic therapy. CLINICAL TRIAL REGISTRATION: URL:
http://www.clinicaltrials.gov. Unique identifier: NCT00391872.
PMID- 29330257
TI - Hemoglobin, Albuminuria, and Kidney Function in Cardiovascular Risk: The ARIC
(Atherosclerosis Risk in Communities) Study.
AB - BACKGROUND: Reduced estimated glomerular filtration rate (eGFR) and elevated
urinary albumin-to-creatinine ratio (ACR) individually increase risk of
cardiovascular disease (CVD). We hypothesized that these associations are
stronger among people with abnormal (both low and high) hemoglobin levels.
METHODS AND RESULTS: Using 5801 participants with available hemoglobin measures
of the ARIC (Atherosclerosis Risk in Community) study in 1996-1998, we explored
the cross-sectional association of eGFR and ACR with hemoglobin levels and their
longitudinal associations with CVD (heart failure, coronary heart disease, and
stroke) risk through 2013. At baseline, 8.8% had anemia (<13 g/dL in men and <12
g/dL in women) and 7.2% had high hemoglobin (>=16 g/dL in men and >=15 g/dL in
women). The adjusted prevalence ratio of anemia was 2.12 (95% confidence
interval, 1.59-2.82) for eGFR 30 to 59 compared with >=90 mL/min per 1.73 m2 and
1.45 (1.07-1.95) for ACR >=30 compared with <10 mg/g. ACR >=30 mg/g was also
associated with high hemoglobin (prevalence ratio, 1.57 [1.12-2.19] compared with
<10 mg/g). During follow-up, there were 1069 incident CVDs among 5098 CVD-free
participants at baseline. In multivariable Cox models, lower eGFR, higher ACR,
and anemia were each independently associated with CVD risk, with the association
of low eGFR being slightly stronger in anemia (P-for-interaction, 0.072). There
was no hemoglobin-ACR interaction; however, when CVD subtypes were analyzed
separately, risk of coronary heart disease and stroke associated with high ACR
was slightly stronger in high hemoglobin (P-for-interaction, 0.074). CONCLUSIONS:
Kidney function, albuminuria, and anemia were correlated and independently
associated with CVD risk. Correlation and potential interaction for
atherosclerotic CVD between albuminuria and high hemoglobin deserve further
investigation.
PMID- 29330259
TI - Limited Accuracy of Administrative Data for the Identification and Classification
of Adult Congenital Heart Disease.
AB - BACKGROUND: Administrative data sets utilize billing codes for research and
quality assessment. Previous data suggest that such codes can accurately identify
adults with congenital heart disease (CHD) in the cardiology clinic, but their
use has yet to be validated in a larger population. METHODS AND RESULTS: All
administrative codes from an entire health system were queried for a single year.
Adults with a CHD diagnosis code (International Classification of Diseases, Ninth
Revision, (ICD-9) codes 745-747) defined the cohort. A previously validated
hierarchical algorithm was used to identify diagnoses and classify patients. All
charts were reviewed to determine a gold standard diagnosis, and comparisons were
made to determine accuracy. Of 2399 individuals identified, 206 had no CHD by the
algorithm or were deemed to have an uncertain diagnosis after provider review. Of
the remaining 2193, only 1069 had a confirmed CHD diagnosis, yielding overall
accuracy of 48.7% (95% confidence interval, 47-51%). When limited to those with
moderate or complex disease (n=484), accuracy was 77% (95% confidence interval,
74-81%). Among those with CHD, misclassification occurred in 23%. The
discriminative ability of the hierarchical algorithm (C statistic: 0.79; 95%
confidence interval, 0.77-0.80) improved further with the addition of age,
encounter type, and provider (C statistic: 0.89; 95% confidence interval, 0.88
0.90). CONCLUSIONS: ICD codes from an entire healthcare system were frequently
erroneous in detecting and classifying CHD patients. Accuracy was higher for
those with moderate or complex disease or when coupled with other data. These
findings should be taken into account in future studies utilizing administrative
data sets in CHD.
PMID- 29330258
TI - Chronic Total Occlusion Percutaneous Coronary Intervention: Evidence and
Controversies.
PMID- 29330261
TI - Conscientious objection in abortion care.
PMID- 29330260
TI - Race and Socioeconomic Status Independently Affect Risk of Major Amputation in
Peripheral Artery Disease.
AB - BACKGROUND: Black race has been shown to be a risk factor for amputation in
peripheral artery disease (PAD); however, race has been argued to be a marker for
socioeconomic status (SES) rather than true disparity. The aim of this study is
to study the impact of race and SES on amputation risk in PAD patients. METHODS
AND RESULTS: Patients with incident PAD in the national Veterans Affairs
Corporate Data Warehouse were identified from 2003 to 2014 (N=155 647). The
exposures were race and SES (measured by median income in residential ZIP codes).
The outcome was incident major amputation. Black veterans were significantly more
likely to live in low-SES neighborhoods and to present with advanced PAD. Black
patients had a higher amputation risk in each SES stratum compared with white
patients. In Cox models (adjusting for covariates), black race was associated
with a 37% higher amputation risk compared with white race (hazard ratio: 1.37;
95% confidence interval, 1.30-1.45), whereas low SES was independently predictive
of increased risk of amputation (hazard ratio: 1.12; 95% confidence interval,
1.06-1.17) and showed no evidence of interaction with race. In predicted
amputation risk analysis, black race and low SES continued to be significant risk
factors for amputation regardless of PAD presentation. CONCLUSIONS: Black race
significantly increases the risk of amputation within the same SES stratum
compared with white race and has an independent effect on limb loss after
controlling for comorbidities, severity of PAD at presentation, and use of
medications.
PMID- 29330263
TI - Senescence-Associated Chromatin Remodeling Promotes Cancer Stemness.
AB - Treatment-induced senescence is associated with stem-cell reprogramming of non
stem cancer cells.
PMID- 29330262
TI - Coffee consumption and health: umbrella review of meta-analyses of multiple
health outcomes.
PMID- 29330264
TI - Ependymoma Superenhancer Profiling Reveals Potential Therapeutic Targets.
AB - Ependymoma superenhancer landscapes delineate molecular subgroups and define
transcriptional circuitries.
PMID- 29330265
TI - FGFR3-TACC3 Activates Mitochondrial Respiration via PIN4 Phosphorylation.
AB - PIN4 is a FGFR3-TACC3 substrate required for ROS-mediated induction of PGCIalpha
and tumor growth.
PMID- 29330266
TI - HIF2alpha Antagonism Has Antitumor Activity in Advanced ccRCC.
AB - The HIF2alpha antagonist PT2385 achieved responses in 14% of patients with
heavily pretreated ccRCC.
PMID- 29330267
TI - Case of acute severe postpartum urinary incontinence: an extravesical
subsphincteric prolapsed ureterocoele.
AB - A 32-year-old woman presents to outpatients 10 days postpartum, with symptoms of
an intermittent vaginal lump and urinary incontinence. Vaginal examination
revealed no demonstrable prolapse or stress incontinence. A swelling in the
bladder was noted during an antenatal scan suggesting a ureterocoele. She was
referred for pelvic floor physiotherapy in the first instance. Forty-eight hours
later, she represented to casualty with discomforting vaginal lump symptoms and
continuous urinary incontinence. At this stage on vaginal inspection, there was
an evident dusky lump emerging from the urethra with continuous incontinence. An
extravesical subsphincteric prolapsed ureterocoele was evident, 5 cm beyond the
external urethral meatus. The diagnosis was confirmed with an MRI scan which
demonstrated the prolapsed obstructing ureterocoele causing significant left
sided hydroureteronephrosis. The ureterocoele was managed with a cystoscopy and
transurethral incision of the ureterocoele under anaesthesia, which facilitated
drainage and resolution. At 3-month postoperatively, the patient remains
continent and satisfied.
PMID- 29330268
TI - Pelvic and buttock hypoplasia reconstructed with anatomical breast implants.
AB - Radiation therapy is used in the management of a number of childhood cancers and
can have significant effects on skeletal growth. We present the case of a 35-year
old woman who developed a hypoplastic pelvis and buttocks following radiotherapy
for rhabdomyosarcoma of the vagina at the age of 2. At the age of 25, the patient
underwent bilateral buttock augmentation with a two-stage reconstruction using
tissue expansion followed by definitive augmentation with anatomical breast
implant insertion. The patient continues to have a satisfactory outcome 10 years
following reconstruction, having undergone a single uplift procedure and exchange
of implants through the original incision 9 years postoperatively. This case
represents a unique reconstructive challenge to plastic surgeons and was
successfully managed with a novel approach.
PMID- 29330269
TI - Central nervous system graft-versus-host disease (CNS-GvHD) after allogeneic
haematopoietic stem cell transplantation.
AB - A 60-year-old man presented with impaired consciousness and psychomotor agitation
after a second allogeneic haematopoietic stem cell transplantation (HSCT) from a
matched unrelated donor for acute myeloid leukaemia. Clinical, biological and
radiological evidence suggested a diagnosis of central nervous system graft
versus-host disease (CNS-GvHD). After intrathecal infusion of methylprednisolone,
the clinical symptoms as well as the radiological abnormalities disappeared. The
present report illustrates the difficulties in the diagnosis and the management
of CNS-GvHD, a very rare and still challenging neurological complication that can
occur after allogeneic HSCT.
PMID- 29330270
TI - Cutis marmorata telangiectatica congenita and major lower limb asymmetry.
AB - A 39-week-old male newborn presented at birth with atrophic erythematous and
purpuric skin lesions, in a typical right-sided segmental distribution. Lesions
were persistent and unaffected by rewarming in the postpartum period. Postnatal
echocardiogram showed a predominance of the right cavities and an upper atrial
septal defect. Cerebral and abdominal ultrasound were normal along with
ophthalmological examination. On follow-up, lower limbs asymmetry was noted. The
right lower limb was shorter in length and had a smaller diameter. At 6 months,
the right lower limb was 1.5 cm shorter than the left, most likely related to
nutritive vessels malformations. The discrepancy was even more pronounced at the
age of 9 months. This leg-length asymmetry can lead to severe functional
limitations in the future.
PMID- 29330271
TI - Vitamin B12 deficiency: unusual cause of jaundice in an adolescent.
AB - Vitamin B12 deficiency in vegans is a known cause of megaloblastic anaemia. We
report an adolescent girl who presented with jaundice and weight loss for 6
months secondary to vitamin B12 deficiency, leading to megaloblastic anaemia.
Replacement with vitamin B12 reversed her symptoms, resulting in weight gain, and
normalised her haemoglobin, red blood cell morphology, bilirubin levels and serum
vitamin B12 levels.
PMID- 29330272
TI - Spontaneous splenic rupture as a rare complication of G-CSF injection.
AB - Splenic rupture is an infrequent and underdiagnosed side effect of granylocyte
colony-stimulating factor (G-CSF). We report the case of a 54-year-old woman with
brain and bone metastasis in a lung adenocarcinoma who was admitted for faintness
28 days after a G-CSF injection. Abdominal CT scan confirmed the diagnosis of
splenic rupture. A conservative treatment was chosen using a peritoneal cleansing
during laparoscopic surgery. Clinicians should be aware of this rare toxicity as
it could be severe, but easily reversible using appropriate surgical treatment.
Even if prognosis remains poor for patients with lung cancer, invasive procedures
could be considered in this rapidly evolving setting, especially in case of
reversible adverse event.
PMID- 29330273
TI - Rheumatoid disease: an unusual cause of relapsing meningoencephalitis.
AB - A 73-year-old man presented with three episodes of dysphasia and disinhibited
behaviour, a single seizure and transient ischaemic attack-like events
characterised by right arm and/or leg weakness. These episodes were separated by
month-long asymptomatic intervals. Medical history included rheumatoid arthritis,
which was clinically quiescent on leflunomide.Repeated cerebrospinal fluid
examination showed a persistent lymphocytosis with mildly reduced glucose and
elevated protein; oligoclonal bands and viral PCR were negative. MRI of the brain
was initially normal, but 7 months after initial presentation revealed meningeal
enhancement with bifrontal cortical hyperintensities on T2/fluid-attenuated
inversion recovery. Brain biopsy demonstrated necrotising granulomatous
meningitis with mixed T cell and B cell infiltrates and without evidence of
vasculitis or infection. Serum anticyclic citrullinated peptide antibodies were
strongly positive.The diagnosis of rheumatoid meningoencephalitis was made on the
basis of brain biopsy findings and serological evidence of active rheumatoid
disease. Steroids and rituximab therapy were started leading to clinical
stabilisation.
PMID- 29330274
TI - Cerebrofacial arteriovenous metameric syndrome with hypopituitarism: a rare
association.
AB - Case of cerebrofacial arteriovenous metameric syndrome (CAMS) in a 9-year-old boy
is described with arteriovenous malformation simultaneously involving the brain
and face, with characteristic CAMS type 1 and 2 involvement. This patient
demonstrates the wide spectrum of clinical manifestations of CAMS, and in this
particular case, the patient exhibits features of hypopituitarism-an association
that was not previously described in the literature to our knowledge. Awareness
of the underlying embryological abnormality and recognition of resultant clinical
and radiological presentations are paramount for diagnosis and treatment.
PMID- 29330275
TI - Case of chest pain in a young man.
AB - A young man with a history of smoking presented with acute-onset chest pain after
lifting weights. He also noticed a change in his voice, tightness in his neck and
difficulty breathing. A chest radiograph showed soft tissue emphysema in the
neck. A CT scan of the chest revealed moderate amount of pneumomediastinum
tracking into the neck and down to the diaphragm. He was haemodynamically stable
and had no hypoxia or dysphagia. He was monitored for 48 hours and discharged
home after resolution of his symptoms. A chest radiograph repeated after 6 weeks
was normal.
PMID- 29330276
TI - Cutaneous Mycobacterium massiliense infection from tattooing: a common yet under
reported and persistent epidemic hazard for dermatologists.
AB - Tattoo popularity continues to rise, with 3 in 10 Americans bearing at least one.
Among tattoo complications, non-tuberculous mycobacteria (NTM) has emerged as a
global public health concern. NTM infections associated with tattooing of
immunocompetent individuals have occurred as sporadic cases and community
outbreaks. Water sources are considered the major pathogenic reservoirs. Tattoo
related inoculation has been linked to contamination of ink, either during the
manufacturing process or during dilution of black ink using non-sterile water.
NTM infections have also been documented in a number of cosmetic and surgical
procedures, including cutaneous surgery, Mohs micrographic surgery, mesotherapy,
liposuction and laser resurfacing. NTM inoculation through exposure to
contaminated water or non-sterile instruments remains a challenge for
dermatologists and risk to patients. We reported a case of cutaneous
Mycobacterium massiliense infection following tattoo placement. This report
underscores the importance of clinicians to consider NTM infections in the
differential diagnosis of procedure-related reactions.
PMID- 29330277
TI - Bancroftian filariasis associated with male sterility.
PMID- 29330278
TI - Multiple cranial nerve palsies secondary to a recurrence of Hansen's disease.
PMID- 29330279
TI - Rare cause of isolated severe coagulation failure in cirrhosis: traditional
healing with fenugreek.
AB - Patients with cirrhosis develop decompensation events during the natural history
of the disease that encompass ascites, variceal bleeding, hepatic encephalopathy
and jaundice. Coagulation failure, defined using the international normalised
ratio, even though not a decompensation event, is important in patients with
stratifying cirrhosis into those who require liver transplantation for long-term
survival. Isolated coagulation failure in cirrhosis is rare and usually occurs
with use of anticoagulants in the setting of vascular diseases. We reported the
case of a patient with compensated cirrhosis in whom, isolated severe coagulation
failure was found to be due to excessive use of fenugreek milk porridge as part
of traditional healing. The coagulation failure was promptly reversed with
avoidance of fenugreek and supplementation with vitamin K.
PMID- 29330280
TI - Cutaneous larva migrans with pulmonary involvement.
PMID- 29330281
TI - Hepatic portal venous gas after diving.
PMID- 29330282
TI - Population-dependent Intron Retention and DNA Methylation in Breast Cancer.
AB - Regulation of gene expression by DNA methylation in gene promoter regions is well
studied; however, the effects of methylation in the gene body (exons and introns)
on gene expression are comparatively understudied. Recently, hypermethylation has
been implicated in the inclusion of alternatively spliced exons; moreover, exon
recognition can be enhanced by recruiting the methyl-CpG-binding protein (MeCP2)
to hypermethylated sites. This study examines whether the methylation status of
an intron is correlated with how frequently the intron is retained during
splicing using DNA methylation and RNA sequencing data from breast cancer tissue
specimens in The Cancer Genome Atlas. Interestingly, hypomethylation of introns
is correlated with higher levels of intron expression in mRNA and the methylation
level of an intron is inversely correlated with its retention in mRNA from the
gene in which it is located. Furthermore, significant population differences were
observed in the methylation level of retained introns. In African-American
donors, retained introns were not only less methylated compared to European
American donors, but also were more highly expressed. This underscores the need
for understanding epigenetic differences in populations and their correlation
with breast cancer is an important step toward achieving personalized cancer
care.Implications: This research contributes to the understanding of how
epigenetic markers in the gene body communicate with the transcriptional
machinery to control transcript diversity and differential biological response to
changes in methylation status could underlie some of the known, yet unexplained,
disparities in certain breast cancer patient populations. Mol Cancer Res; 16(3);
461-9. (c)2018 AACR.
PMID- 29330284
TI - Novel Intergenically Spliced Chimera, NFATC3-PLA2G15, Is Associated with
Aggressive T-ALL Biology and Outcome.
AB - Leukemias are frequently characterized by the expression of oncogenic fusion
chimeras that normally arise due to chromosomal rearrangements. Intergenically
spliced chimeric RNAs (ISC) are transcribed in the absence of structural genomic
changes, and aberrant ISC expression is now recognized as a potential driver of
cancer. To better understand these potential oncogenic drivers, high-throughput
RNA sequencing was performed on T-acute lymphoblastic leukemia (T-ALL) patient
specimens (n = 24), and candidate T-ALL-related ISCs were identified (n = 55; a
median of 4/patient). In-depth characterization of the NFATC3-PLA2G15 chimera,
which was variably expressed in primary T-ALL, was performed. Functional
assessment revealed that the fusion had lower activity than wild-type NFATC3 in
vitro, and T-ALLs with elevated NFATC3-PLA2G15 levels had reduced transcription
of canonical NFAT pathway genes in vivo Strikingly, high expression of the NFATC3
PLA2G15 chimera correlated with aggressive disease biology in murine patient
derived T-ALL xenografts, and poor prognosis in human T-ALL patients. Mol Cancer
Res; 16(3); 470-5. (c)2018 AACR.
PMID- 29330283
TI - Centriole Overduplication is the Predominant Mechanism Leading to Centrosome
Amplification in Melanoma.
AB - Centrosome amplification (CA) is common in cancer and can arise by centriole
overduplication or by cell doubling events, including the failure of cell
division and cell-cell fusion. To assess the relative contributions of these two
mechanisms, the number of centrosomes with mature/mother centrioles was examined
by immunofluorescence in a tissue microarray of human melanomas and benign nevi
(n = 79 and 17, respectively). The centrosomal protein 170 (CEP170) was used to
identify centrosomes with mature centrioles; this is expected to be present in
most centrosomes with cell doubling, but on fewer centrosomes with
overduplication. Using this method, it was determined that the majority of CA in
melanoma can be attributed to centriole overduplication rather than cell doubling
events. As Polo-like kinase 4 (PLK4) is the master regulator of centriole
duplication, the hypothesis that PLK4 overexpression contributes to centriole
overduplication was evaluated. PLK4 is significantly overexpressed in melanoma
compared with benign nevi and in a panel of human melanoma cell lines (A375,
Hs294T, G361, WM35, WM115, 451Lu, and SK-MEL-28) compared with normal human
melanocytes. Interestingly, although PLK4 expression did not correlate with CA in
most cases, treatment of melanoma cells with a selective small-molecule PLK4
inhibitor (centrinone B) significantly decreased cell proliferation. The
antiproliferative effects of centrinone B were also accompanied by induction of
apoptosis.Implications: This study demonstrates that centriole overduplication is
the predominant mechanism leading to centrosome amplification in melanoma and
that PLK4 should be further evaluated as a potential therapeutic target for
melanoma treatment. Mol Cancer Res; 16(3); 517-27. (c)2018 AACR.
PMID- 29330285
TI - Foxo-dependent Par-4 Upregulation Prevents Long-term Survival of Residual Cells
Following PI3K-Akt Inhibition.
AB - Tumor recurrence is a leading cause of death and is thought to arise from a
population of residual cells that survive treatment. These residual cancer cells
can persist, locally or at distant sites, for years or decades. Therefore,
understanding the pathways that regulate residual cancer cell survival may
suggest opportunities for targeting these cells to prevent recurrence.
Previously, it was observed that the proapoptotic protein (PAWR/Par-4) negatively
regulates residual cell survival and recurrence in mice and humans. However, the
mechanistic underpinnings on how Par-4 expression is regulated are unclear. Here,
it is demonstrated that Par-4 is transcriptionally upregulated following
treatment with multiple drugs targeting the PI3K-Akt-mTOR signaling pathway, and
identify the Forkhead family of transcription factors as mediators of this
upregulation. Mechanistically, Foxo3a directly binds to the Par-4 promoter and
activates its transcription following inhibition of the PI3K-Akt pathway. This
Foxo-dependent Par-4 upregulation limits the long-term survival of residual cells
following treatment with therapeutics that target the PI3K-Akt pathway. Taken
together, these results indicate that residual breast cancer tumor cell survival
and recurrence requires circumventing Foxo-driven Par-4 upregulation and suggest
that approaches to enforce Par-4 expression may prevent residual cell survival
and recurrence. Mol Cancer Res; 16(4); 599-609. (c)2018 AACR.
PMID- 29330287
TI - Targeted AKT Inhibition in Prostate Cancer Cells and Spheroids Reduces Aerobic
Glycolysis and Generation of Hyperpolarized [1-13C] Lactate.
AB - The PI3K/AKT/mTOR (PAM) signaling pathway is frequently mutated in prostate
cancer. Specific AKT inhibitors are now in advanced clinical trials, and this
study investigates the effect of MK2206, a non-ATP-competitive inhibitor, on the
cellular metabolism of prostate cancer cells. We observed a reduction in cell
motility and aerobic glycolysis in prostate cancer cells with treatment. These
changes were not accompanied by a reduction in the ratio of high-energy
phosphates or a change in total protein levels of enzymes and transporters
involved in glycolysis. However, a decreased ratio of NAD+/NADH was observed,
motivating the use of hyperpolarized magnetic resonance spectroscopy (HP-MRS) to
detect treatment response. Spectroscopic experiments were performed on tumor
spheroids, 3D structures that self-organize in the presence of an extracellular
matrix. Treated spheroids showed decreased lactate production with on-target
inhibition confirmed using IHC, demonstrating that HP-MRS can be used to probe
treatment response in prostate cancer spheroids and can provide a biomarker for
treatment response. Mol Cancer Res; 16(3); 453-60. (c)2018 AACR.
PMID- 29330286
TI - Agonist-induced CXCR4 and CB2 Heterodimerization Inhibits Galpha13/RhoA-mediated
Migration.
AB - G-protein-coupled receptor (GPCR) heterodimerization has emerged as a means by
which alternative signaling entities can be created; yet, how receptor
heterodimers affect receptor pharmacology remains unknown. Previous observations
suggested a biochemical antagonism between GPCRs, CXCR4 and CB2 (CNR2), where
agonist-bound CXCR4 and agonist-bound CB2 formed a physiologically nonfunctional
heterodimer on the membrane of cancer cells, inhibiting their metastatic
potential in vitro However, the reduced signaling entities responsible for the
observed functional outputs remain elusive. This study now delineates the
signaling mechanism whereby heterodimeric association between CXCR4 and CB2,
induced by simultaneous agonist treatment, results in decreased CXCR4-mediated
cell migration, invasion, and adhesion through inhibition of the Galpha13/RhoA
signaling axis. Activation of CXCR4 by its cognate ligand, CXCL12, stimulates
Galpha13 (GNA13), and subsequently, the small GTPase RhoA, which is required for
directional cell migration and the metastatic potential of cancer cells. These
studies in prostate cancer cells demonstrate decreased protein expression levels
of Galpha13 and RhoA upon simultaneous CXCR4/CB2 agonist stimulation.
Furthermore, the agonist-induced heterodimer abrogated RhoA-mediated cytoskeletal
rearrangement resulting in the attenuation of cell migration and invasion of an
endothelial cell barrier. Finally, a reduction was observed in the expression of
integrin alpha5 (ITGA5) upon heterodimerization, supported by decreased cell
adhesion to extracellular matrices in vitro Taken together, the data identify a
novel pharmacologic mechanism for the modulation of tumor cell migration and
invasion in the context of metastatic disease.Implications: This study
investigates a signaling mechanism by which GPCR heterodimerization inhibits
cancer cell migration. Mol Cancer Res; 16(4); 728-39. (c)2018 AACR.
PMID- 29330288
TI - Epigenetically Regulated Chromosome 14q32 miRNA Cluster Induces Metastasis and
Predicts Poor Prognosis in Lung Adenocarcinoma Patients.
AB - Most lung cancer deaths are related to metastases, which indicates the necessity
of detecting and inhibiting tumor cell dissemination. Here, we aimed to identify
miRNAs involved in metastasis of lung adenocarcinoma as prognostic biomarkers and
therapeutic targets. To that end, lymph node metastasis-associated miRNAs were
identified in The Cancer Genome Atlas lung adenocarcinoma patient cohort
(sequencing data; n = 449) and subsequently validated by qRT-PCR in an
independent clinical cohort (n = 108). Overexpression of miRNAs located on
chromosome 14q32 was associated with metastasis in lung adenocarcinoma patients.
Importantly, Kaplan-Meier analysis and log-rank test revealed that higher
expression levels of individual 14q32 miRNAs (mir-539, mir-323b, and mir-487a)
associated with worse disease-free survival of never-smoker patients. Epigenetic
analysis including DNA methylation microarray data and bisulfite sequencing
validation demonstrated that the induction of 14q32 cluster correlated with
genomic hypomethylation of the 14q32 locus. CRISPR activation technology, applied
for the first time to functionally study the increase of clustered miRNA levels
in a coordinated manner, showed that simultaneous overexpression of 14q32 miRNAs
promoted tumor cell migratory and invasive properties. Analysis of individual
miRNAs by mimic transfection further illustrated that miR-323b-3p, miR-487a-3p,
and miR-539-5p significantly contributed to the invasive phenotype through the
indirect regulation of different target genes. In conclusion, overexpression of
14q32 miRNAs, associated with the respective genomic hypomethylation, promotes
metastasis and correlates with poor patient prognosis in lung
adenocarcinoma.Implications: This study points to chromosome 14q32 miRNAs as
promising targets to inhibit tumor cell dissemination and to predict patient
prognosis in lung adenocarcinoma. Mol Cancer Res; 16(3); 390-402. (c)2018 AACR.
PMID- 29330289
TI - BRCA1 through Its E3 Ligase Activity Regulates the Transcription Factor Oct1 and
Carbohydrate Metabolism.
AB - The tumor suppressor BRCA1 regulates the DNA damage response (DDR) and other
processes that remain incompletely defined. Among these, BRCA1 heterodimerizes
with BARD1 to ubiquitylate targets via its N-terminal E3 ligase activity. Here,
it is demonstrated that BRCA1 promotes oxidative metabolism by degrading Oct1
(POU2F1), a transcription factor with proglycolytic and tumorigenic effects.
BRCA1 E3 ubiquitin ligase mutation skews cells toward a glycolytic metabolic
profile while elevating Oct1 protein. CRISPR-mediated Oct1 deletion reverts the
glycolytic phenotype. RNA sequencing (RNAseq) confirms deregulation of metabolic
genes downstream of Oct1. BRCA1 mediates Oct1 ubiquitylation and degradation, and
mutation of two ubiquitylated Oct1 lysines insulates the protein against BRCA1
mediated destabilization. Oct1 deletion in MCF-7 breast cancer cells does not
perturb growth in standard culture, but inhibits growth in soft agar and
xenograft assays. In primary breast cancer clinical specimens, Oct1 protein
levels correlate positively with tumor aggressiveness and inversely with BRCA1.
These results identify BRCA1 as an Oct1 ubiquitin ligase that catalyzes Oct1
degradation to promote oxidative metabolism and restrict tumorigenicity. Mol
Cancer Res; 16(3); 439-52. (c)2018 AACR.
PMID- 29330290
TI - Dual Inhibition of CDK4 and CDK2 via Targeting p27 Tyrosine Phosphorylation
Induces a Potent and Durable Response in Breast Cancer Cells.
AB - Cyclin-dependent kinase 4/6 (CDK4/6)-specific inhibitors, such as palbociclib,
have shown clinical efficacy, but primary or secondary resistance has emerged as
a problem. To develop more effective therapeutic approaches, investigation is
needed into the mechanisms of resistance or adaption. Here, it is demonstrated
that CDK2 compensates for loss of CDK4 activity to rescue palbociclib-arrested
breast cancer cells, suggesting that inhibition of both kinases is required to
achieve durable response. In addition, a novel strategy is described to inhibit
tyrosine phosphorylation of p27Kip1 (CDKN1B) and simultaneously inhibit both CDK2
and CDK4. p27Kip1 is a required assembly factor for cyclin-CDK4 complexes, but it
must be phosphorylated on residue Y88 to open or activate the complex. The Brk
SH3 peptide, ALT, blocks p27 Y88 phosphorylation, inhibiting CDK4.
Nonphosphorylated p27 is no longer a target for ubiquitin-mediated degradation
and this stabilized p27 now also inhibits CDK2 activity. Thus, ALT induction
inhibits both the kinase that drives proliferation (CDK4) and the kinase that
mediates resistance (CDK2), causing a potent and long-lasting cell-cycle arrest.
ALT arrests growth of all breast cancer subgroups and synergizes with palbociclib
to increase cellular senescence and to cause tumor regression in breast cancer
xenograft models. The use of ALT demonstrates that both CDK4 and CDK2 need to be
inhibited if long-term efficacy is to be achieved and represents a novel modality
to inhibit breast cancer cells.Implications: Modulating tyrosine phosphorylation
of p27 impacts both proliferative (CDK4) and resistance (CDK2) mechanisms in
breast cancer and suggests that phospho-p27 status may serve as a biomarker for
patients that are responsive to CDK4/6 inhibition. Mol Cancer Res; 16(3); 361-77.
(c)2018 AACR.
PMID- 29330291
TI - Keap1 Inhibits Metastatic Properties of NSCLC Cells by Stabilizing Architectures
of F-Actin and Focal Adhesions.
AB - Low expression of the tumor suppressor Kelch-like ECH-associated protein 1
(KEAP1) in non-small cell lung cancer (NSCLC) often results in higher malignant
biological behavior and poor prognosis; however, the underlying mechanism remains
unclear. The present study demonstrates that overexpression of Keap1
significantly suppresses migration and invasion of three different lung cancer
cells (A549, H460, and H1299). Highly expressed Keap1, compared with the control,
promotes formation of multiple stress fibers with larger mature focal adhesion
complexes in the cytoplasm where only fine focal adhesions were observed in the
membrane under control conditions. RhoA activity significantly increased when
Keap1 was overexpressed, whereas Myosin 9b expression was reduced but could be
rescued by proteasome inhibition. Noticeably, mouse tumor xenografts with Keap1
overexpression were smaller in size and less metastatic relative to the control
group. Taken together, these results demonstrate that Keap1 stabilizes F-actin
cytoskeleton structures and inhibits focal adhesion turnover, thereby restraining
the migration and invasion of NSCLC. Therefore, increasing Keap1 or targeting its
downstream molecules might provide potential therapeutic benefits for the
treatment of patients with NSCLC.Implications: This study provides mechanistic
insight on the metastatic process in NSCLC and suggests that Keap1 and its
downstream molecules may be valuable drug targets for NSCLC patients. Mol Cancer
Res; 16(3); 508-16. (c)2018 AACR.
PMID- 29330292
TI - Microenvironment-Derived Regulation of HIF Signaling Drives Transcriptional
Heterogeneity in Glioblastoma Multiforme.
AB - The evolving and highly heterogeneous nature of malignant brain tumors underlies
their limited response to therapy and poor prognosis. In addition to genetic
alterations, highly dynamic processes, such as transcriptional and metabolic
reprogramming, play an important role in the development of tumor heterogeneity.
The current study reports an adaptive mechanism in which the metabolic
environment of malignant glioma drives transcriptional reprogramming.
Multiregional analysis of a glioblastoma patient biopsy revealed a metabolic
landscape marked by varying stages of hypoxia and creatine enrichment. Creatine
treatment and metabolism was further shown to promote a synergistic effect
through upregulation of the glycine cleavage system and chemical regulation of
prolyl-hydroxylase domain. Consequently, creatine maintained a reduction of
reactive oxygen species and change of the alpha-ketoglutarate/succinate ratio,
leading to an inhibition of HIF signaling in primary tumor cell lines. These
effects shifted the transcriptional pattern toward a proneural subtype and
reduced the rate of cell migration and invasion in vitroImplications:
Transcriptional subclasses of glioblastoma multiforme are heterogeneously
distributed within the same tumor. This study uncovered a regulatory function of
the tumor microenvironment by metabolism-driven transcriptional reprogramming in
infiltrating glioma cells. Mol Cancer Res; 16(4); 655-68. (c)2018 AACR.
PMID- 29330294
TI - Establishment of the First Well-differentiated Human Pancreatic Neuroendocrine
Tumor Model.
AB - Clinical options for systemic therapy of neuroendocrine tumors (NET) are limited.
Development of new drugs requires suitable representative in vitro and in vivo
model systems. So far, the unavailability of a human model with a well
differentiated phenotype and typical growth characteristics has impaired
preclinical research in NET. Herein, we establish and characterize a lymph node
derived cell line (NT-3) from a male patient with well-differentiated pancreatic
NET. Neuroendocrine differentiation and tumor biology was compared with existing
NET cell lines BON and QGP-1. In vivo growth was assessed in a xenograft mouse
model. The neuroendocrine identity of NT-3 was verified by expression of multiple
NET-specific markers, which were highly expressed in NT-3 compared with BON and
QGP-1. In addition, NT-3 expressed and secreted insulin. Until now, this well
differentiated phenotype is stable since 58 passages. The proliferative labeling
index, measured by Ki-67, of 14.6% +/- 1.0% in NT-3 is akin to the original tumor
(15%-20%), and was lower than in BON (80.6% +/- 3.3%) and QGP-1 (82.6% +/- 1.0%).
NT-3 highly expressed somatostatin receptors (SSTRs: 1, 2, 3, and 5). Upon
subcutaneous transplantation of NT-3 cells, recipient mice developed tumors with
an efficient tumor take rate (94%) and growth rate (139% +/- 13%) by 4 weeks.
Importantly, morphology and neuroendocrine marker expression of xenograft tumors
resembled the original human tumor.Implications: High expression of somatostatin
receptors and a well-differentiated phenotype as well as a slow growth rate
qualify the new cell line as a relevant model to study neuroendocrine tumor
biology and to develop new tumor treatments. Mol Cancer Res; 16(3); 496-507.
(c)2018 AACR.
PMID- 29330295
TI - Epigenetic Reprogramming of Pericentromeric Satellite DNA in Premalignant and
Malignant Lesions.
AB - Repression of repetitive DNA is important for maintaining genomic stability, but
is often perturbed in cancer. For instance, the megabase satellite domain at
chromosome 1q12 is a common site of genetic rearrangements, such as
translocations and deletions. Polycomb-group proteins can be observed as large
subnuclear domains called polycomb bodies, the composition and cellular function
of which has remained elusive. This study demonstrates that polycomb bodies are
canonical subunits of the multiprotein polycomb repressive complex 1 deposited on
1q12 pericentromeric satellite DNA, which are normally maintained as constitutive
heterochromatin by other mechanisms. Furthermore, the data reveal that polycomb
bodies are exclusive to premalignant and malignant cells, being absent in normal
cells. For instance, polycomb bodies are present in melanocytic cells of nevi and
conserved in primary and metastatic melanomas. Deposition of polycomb on the 1q12
satellite DNA in melanoma development correlated with reduced DNA methylation
levels. In agreement with this, inhibition of DNA methyltransferases, with the
hypomethylating agent guadecitabine (SGI-110), was sufficient for polycomb body
formation on pericentromeric satellites in primary melanocytes. This suggests
that polycomb bodies form in cancer cells with global DNA demethylation to
control the stability of pericentromeric satellite DNA. These results reveal a
novel epigenetic perturbation specific to premalignant and malignant cells that
may be used as an early diagnostic marker for detection of precancerous changes
and a new therapeutic entry point.Implications: Pericentromeric satellite DNA is
epigenetically reprogrammed into polycomb bodies as a premalignant event with
implications for transcriptional activity and genomic stability. Mol Cancer Res;
16(3); 417-27. (c)2018 AACR.
PMID- 29330293
TI - Differential Regulation of LET-7 by LIN28B Isoform-Specific Functions.
AB - The RNA-binding protein LIN28B plays an important role in development, stem cell
biology, and tumorigenesis. LIN28B has two isoforms: the LIN28B-long and -short
isoforms. Although studies have revealed the functions of the LIN28B-long isoform
in tumorigenesis, the role of the LIN28B-short isoform remains unclear and
represents a major gap in the field. The LIN28B-long and -short isoforms are
expressed in a subset of human colorectal cancers and adjacent normal colonic
mucosa, respectively. To elucidate the functional and mechanistic aspects of
these isoforms, colorectal cancer cells (Caco-2 and LoVo) were generated to
either express no LIN28B or the -short or -long isoform. Interestingly, the long
isoform suppressed LET-7 expression and activated canonical RAS/ERK signaling,
whereas the short isoform did not. The LIN28B-long isoform-expressing cells
demonstrated increased drug resistance to 5-fluorouracil and cisplatin through
the upregulation of ERCC1, a DNA repair gene, in a LET-7-dependent manner. The
LIN28B-short isoform preserved its ability to bind pre-let-7, without inhibiting
the maturation of LET-7, and competed with the LIN28B-long isoform for binding to
pre-let-7 Coexpression of the short isoform in the LIN28B-long isoform-expressing
cells rescued the phenotypes induced by the LIN28B-long isoform.Implications:
This study demonstrates the differential antagonistic functions of the LIN28B
short isoform against the LIN28B-long isoform through an inability to degrade LET
7, which leads to the novel premise that the short isoform may serve to
counterbalance the long isoform during normal colonic epithelial homeostasis, but
its downregulation during colonic carcinogenesis may reveal the protumorigenic
effects of the long isoform. Mol Cancer Res; 16(3); 403-16. (c)2018 AACR.
PMID- 29330296
TI - Tumor Progression Is Mediated by Thymosin-beta4 through a TGFbeta/MRTF Signaling
Axis.
AB - Although enhanced thymosin beta4 (TMSB4X/Tbeta4) expression is associated with
tumor progression and metastasis, its tumor-promoting functions remain largely
unknown. Here, it is demonstrated that TGFbeta facilitates Tbeta4 expression and
leads to the activation of myocardin-related transcription factors (MRTF), which
are coactivators of serum response factor (SRF) and regulate the expression of
genes critical for the epithelial-mesenchymal transition (EMT) and tumor
metastasis. In murine mammary gland cells (NMuMG), Tbeta4 upregulation is
required for full induction of a MRTF-regulated EMT gene expression program after
TGFbeta stimulation. Tbeta4 levels are transcriptionally regulated via the novel
cis-acting element AGACAAAG, which interacts with Smad and T-cell factor/lymphoid
enhancer factor (TCF/LEF) to synergistically activate the Tbeta4 promoter
downstream of TGFbeta. Murine skin melanoma cells (B16F0 and B16F1) also show the
expression regulation of Tbeta4 by Smad and TCF/LEF. Tbeta4-knockout B16F1
(Tbeta4 KO) clones show significantly diminished expression level of tumor
associated genes, which is regulated by the TGFbeta/MRTFs pathway. In multiple
human cancers, Tbeta4 levels correlate positively with TGFbeta1 and the tumor
associated gene expression levels through processes that respectively depend on
TGFbeta receptor 1 (TGFBR1) and MRTF expression. Kaplan-Meier survival analyses
demonstrate that high Tbeta4 expression associates with poor prognosis in an SRF
expression-dependent manner in several cancers. In mice, Tbeta4 KO clones show
significantly decreased experimental metastatic potential; furthermore, ectopic
expression of constitutively active MRTF-A fully restores the diminished
metastatic activity. In conclusion, the TGFbeta/Tbeta4/MRTF/SRF pathway is
critical for metastasis and tumor progression.Implications: These findings define
a molecular mechanism underlying a tumor-promoting function of thymosin beta4
through activation of MRTF/SRF signaling. Mol Cancer Res; 16(5); 880-93. (c)2018
AACR.
PMID- 29330298
TI - Stemness Is Enhanced in Gastric Cancer by a SET/PP2A/E2F1 Axis.
AB - Gastric cancer is the fifth most common malignancy and the third leading cause of
cancer-related deaths worldwide. Chemotherapies against gastric cancer often
fail, with cancer recurrence due potentially to the persistence of cancer stem
cells. This unique subpopulation of cells in tumors possesses the ability to self
renew and dedifferentiate. These cancer stem cells are critical for initiation,
maintenance, metastasis, and relapse of cancers; however, the molecular
mechanisms supporting cancer stemness remain largely unknown. Increased kinase
and decreased phosphatase activity are hallmarks of oncogenic signaling. Protein
phosphatase 2A (PP2A) functions as a tumor-suppressor enzyme, and elevated levels
of SET/I2PP2A, an endogenous PP2A protein inhibitor, are correlated with poor
prognosis of several human cancers. Here, it was determined that SET expression
was elevated in tumor tissue in a gastric cancer mouse model system, and SET
expression was positively correlated with poor survival of human gastric cancer
patients. Mechanistically, SET knockdown decreased E2F1 levels and suppressed the
stemness of cancer cell lines. Immunoprecipitations show SET associated with the
PP2A-B56 complex, and the B56 subunit interacted with the E2F1 transcription
factor. Treatment of gastric cancer cells with the SET-targeting drug OP449
increased PP2A activity, decreased E2F1 protein levels, and suppressed stemness
of cancer cells. These data indicate that a SET/PP2A/E2F1 axis regulates cancer
cell stemness and is a potential target for gastric cancer therapy.Implications:
This study highlights the oncogenic role of SET/I2PP2A in gastric cancer and
suggests that SET maintains cancer cell stemness by suppressing PP2A activity and
stabilizing E2F1. Mol Cancer Res; 16(3); 554-63. (c)2018 AACR.
PMID- 29330297
TI - Characterization and Evidence of the miR-888 Cluster as a Novel Cancer Network in
Prostate.
AB - Prostate cancer afflicts 1 in 7 men and is the second leading cause of male
cancer-related deaths in the United States. MicroRNAs (miRNAs), an extensive
class of approximately 22 nucleotide noncoding RNAs, are often aberrantly
expressed in tissues and fluids from prostate cancer patients, but the mechanisms
of how specific miRNAs regulate prostate tumorigenesis and metastasis are poorly
understood. Here, miR-888 was identified as a novel prostate factor that promotes
proliferation and migration. miR-888 resides within a genomic cluster of 7 miRNA
genes (mir-892c, mir-890, mir-888, mir-892a, mir-892b, mir-891b, mir-891a) on
human chromosome Xq27.3. Moreover, as miR-888 maps within HPCX1, a locus
associated with susceptibility and/or hereditary prostate cancer, it was
hypothesized that additional miRNA cluster members also play functional roles in
the prostate. Expression analysis determined that cluster members were similarly
elevated in metastatic PC3-ML prostate cells and their secreted exosomes, as well
as enriched in expressed prostatic secretions urine-derived exosomes obtained
from clinical patients with high-grade prostate cancer. In vitro assays revealed
that miR-888 cluster members selectively modulated PC3-derived and LNCaP cell
proliferation, migration, invasion, and colony formation. Mouse xenograft studies
verified miR-888 and miR-891a as pro-oncogenic factors that increased prostate
tumor growth in vivo Further analysis validated RBL1, KLF5, SMAD4, and TIMP2 as
direct miR-888 targets and that TIMP2 is also coregulated by miR-891a. This study
provides the first comprehensive analysis of the entire miR-888 cluster and
reveals biological insight.Implications: This work reveals a complex noncoding
RNA network in the prostate that could be developed as effective diagnostic and
therapeutic tools for advanced prostate cancer. Mol Cancer Res; 16(4); 669-81.
(c)2018 AACR.
PMID- 29330299
TI - Effects of allelic variations in the human myxovirus resistance protein A on its
antiviral activity.
AB - Only a minority of patients infected with seasonal influenza A viruses exhibit a
severe or fatal outcome of infection, but the reasons for this inter-individual
variability in influenza susceptibility are unclear. To gain further insights
into the molecular mechanisms underlying this variability, we investigated
naturally occurring allelic variations of the myxovirus resistance 1 (MX1) gene
coding for the influenza restriction factor MxA. The interferon-induced dynamin
like GTPase consists of an N-terminal GTPase domain, a bundle signaling element,
and a C-terminal stalk responsible for oligomerization and viral target
recognition. We used online databases to search for variations in the MX1 gene.
Deploying in vitro approaches, we found that non-synonymous variations in the
GTPase domain cause the loss of antiviral and enzymatic activities. Furthermore,
we showed that these amino acid substitutions disrupt the interface for GTPase
domain dimerization required for the stimulation of GTP hydrolysis. Variations in
the stalk were neutral or slightly enhanced or abolished MxA antiviral function.
Remarkably, two other stalk variants altered MxA's antiviral specificity.
Variations causing the loss of antiviral activity were found only in heterozygous
carriers. Interestingly, the inactive stalk variants blocked the antiviral
activity of WT MxA in a dominant-negative way, suggesting that heterozygotes are
phenotypically MxA-negative. In contrast, the GTPase-deficient variants showed no
dominant-negative effect, indicating that heterozygous carriers should remain
unaffected. Our results demonstrate that naturally occurring mutations in the
human MX1 gene can influence MxA function, which may explain individual
variations in influenza virus susceptibility in the human population.
PMID- 29330300
TI - Real-time imaging of yeast cells reveals several distinct mechanisms of curing of
the [URE3] prion.
AB - The [URE3] yeast prion is the self-propagating amyloid form of the Ure2 protein.
[URE3] is cured by overexpression of several yeast proteins, including Ydj1,
Btn2, Cur1, Hsp42, and human DnaJB6. To better understand [URE3] curing, we used
real-time imaging with a yeast strain expressing a GFP-labeled full-length Ure2
construct to monitor the curing of [URE3] over time. [URE3] yeast cells exhibited
numerous fluorescent foci, and expression of the GFP-labeled Ure2 affected
neither mitotic stability of [URE3] nor the rate of [URE3] curing by the curing
proteins. Using guanidine to cure [URE3] via Hsp104 inactivation, we found that
the fluorescent foci are progressively lost as the cells divide until they are
cured; the fraction of cells that retained the foci was equivalent to the [URE3]
cell fraction measured by a plating assay, indicating that the foci were the
prion seeds. During the curing of [URE3] by Btn2, Cur1, Hsp42, or Ydj1
overexpression, the foci formed aggregates, many of which were 0.5 MUm or greater
in size, and [URE3] was cured by asymmetric segregation of the aggregated seeds.
In contrast, DnaJB6 overexpression first caused a loss of detectable foci in
cells that were still [URE3] before there was complete dissolution of the seeds,
and the cells were cured. We conclude that GFP labeling of full-length Ure2
enables differentiation among the different [URE3]-curing mechanisms, including
inhibition of severing followed by seed dilution, seed clumping followed by
asymmetric segregation between mother and daughter cells, and seed dissolution.
PMID- 29330301
TI - Genetic control of predominantly error-free replication through an acrolein
derived minor-groove DNA adduct.
AB - Acrolein, an alpha,beta-unsaturated aldehyde, is generated in vivo as the end
product of lipid peroxidation and from metabolic oxidation of polyamines, and it
is a ubiquitous environmental pollutant. The reaction of acrolein with the N2 of
guanine in DNA leads to the formation of gamma-hydroxy-1-N2-propano-2'
deoxyguanosine (gamma-HOPdG), which can exist in DNA in a ring-closed or a ring
opened form. Here, we identified the translesion synthesis (TLS) DNA polymerases
(Pols) that conduct replication through the permanently ring-opened reduced form
of gamma-HOPdG ((r) gamma-HOPdG) and show that replication through this adduct is
mediated via Rev1/Poleta-, Poliota/Polkappa-, and Poltheta-dependent pathways,
respectively. Based on biochemical and structural studies, we propose a role for
Rev1 and Poliota in inserting a nucleotide (nt) opposite the adduct and for Pols
eta and kappa in extending synthesis from the inserted nt in the respective TLS
pathway. Based on genetic analyses and biochemical studies with Poltheta, we
infer a role for Poltheta at both the nt insertion and extension steps of TLS.
Whereas purified Rev1 and Poltheta primarily incorporate a C opposite (r) gamma
HOPdG, Poliota incorporates a C or a T opposite the adduct; nevertheless, TLS
mediated by the Poliota-dependent pathway as well as by other pathways occurs in
a predominantly error-free manner in human cells. We discuss the implications of
these observations for the mechanisms that could affect the efficiency and
fidelity of TLS Pols.
PMID- 29330302
TI - Controlled dimerization of insulin-like growth factor-1 and insulin receptors
reveals shared and distinct activities of holo and hybrid receptors.
AB - Breast cancer development and progression are influenced by insulin-like growth
factor receptor 1 (IGF1R) and insulin receptor (InsR) signaling, which drive
cancer phenotypes such as cell growth, proliferation, and migration. IGF1R and
InsR form IGF1R/InsR hybrid receptors (HybRs) consisting of one molecule of IGF1R
and one molecule of InsR. The specific signaling and functions of HybR are
largely unknown, as HybR is activated by both IGF1 and insulin, and no cellular
system expresses HybR in the absence of holo-IGF1R or holo-InsR. Here we studied
the role of HybR by constructing inducible chimeric receptors and compared HybR
signaling with that of holo-IGF1R and holo-InsR. We cloned chemically inducible
chimeric IGF1R and InsR constructs consisting of the extracellular domains of the
p75 nerve growth factor receptor fused to the intracellular beta subunit of IGF1R
or InsR and a dimerization domain. Dimerization with the drugs AP20187 or AP21967
allowed specific and independent activation of holo-IGF1R, holo-InsR, or HybR,
resulting in activation of the PI3K pathway. Holo-IGF1R and HybR both promoted
cell proliferation and glucose uptake, whereas holo-InsR only promoted glucose
uptake, and only holo-IGF1R showed anti-apoptotic effects. We also found that the
three receptors differentially regulated gene expression: holo-IGF1R and HybR up
regulated EGR3; holo-InsR specifically down-regulated JUN and BCL2L1; holo-InsR
down-regulated but HybR up-regulated HK2; and HybR specifically up-regulated
FHL2, ITGA6, and PCK2. Our findings suggest that, when expressed and activated in
mammary epithelial cells, HybR acts in a manner similar to IGF1R and support
further investigation of the role of HybR in breast cancer.
PMID- 29330303
TI - Mammalian amyloidogenic proteins promote prion nucleation in yeast.
AB - Fibrous cross-beta aggregates (amyloids) and their transmissible forms (prions)
cause diseases in mammals (including humans) and control heritable traits in
yeast. Initial nucleation of a yeast prion by transiently overproduced prion
forming protein or its (typically, QN-rich) prion domain is efficient only in the
presence of another aggregated (in most cases, QN-rich) protein. Here, we
demonstrate that a fusion of the prion domain of yeast protein Sup35 to some non
QN-rich mammalian proteins, associated with amyloid diseases, promotes nucleation
of Sup35 prions in the absence of pre-existing aggregates. In contrast, both a
fusion of the Sup35 prion domain to a multimeric non-amyloidogenic protein and
the expression of a mammalian amyloidogenic protein that is not fused to the
Sup35 prion domain failed to promote prion nucleation, further indicating that
physical linkage of a mammalian amyloidogenic protein to the prion domain of a
yeast protein is required for the nucleation of a yeast prion. Biochemical and
cytological approaches confirmed the nucleation of protein aggregates in the
yeast cell. Sequence alterations antagonizing or enhancing amyloidogenicity of
human amyloid-beta (associated with Alzheimer's disease) and mouse prion protein
(associated with prion diseases), respectively, antagonized or enhanced
nucleation of a yeast prion by these proteins. The yeast-based prion nucleation
assay, developed in our work, can be employed for mutational dissection of
amyloidogenic proteins. We anticipate that it will aid in the identification of
chemicals that influence initial amyloid nucleation and in searching for new
amyloidogenic proteins in a variety of proteomes.
PMID- 29330304
TI - Efficient prion disease transmission through common environmental materials.
AB - Prion diseases are a group of fatal neurodegenerative diseases associated with a
protein-based infectious agent, termed prion. Compelling evidence suggests that
natural transmission of prion diseases is mediated by environmental contamination
with infectious prions. We hypothesized that several natural and man-made
materials, commonly found in the environments of wild and captive animals, can
bind prions and may act as vectors for disease transmission. To test our
hypothesis, we exposed surfaces composed of various common environmental
materials (i.e. wood, rocks, plastic, glass, cement, stainless steel, aluminum,
and brass) to hamster-adapted 263K scrapie prions and studied their attachment
and retention of infectivity in vitro and in vivo Our results indicated that
these surfaces, with the sole exception of brass, efficiently bind, retain, and
release prions. Prion replication was studied in vitro using the protein
misfolding cyclic amplification technology, and infectivity of surface-bound
prions was analyzed by intracerebrally challenging hamsters with contaminated
implants. Our results revealed that virtually all prion-contaminated materials
transmitted the disease at high rates. To investigate a more natural form of
exposure to environmental contamination, we simply housed animals with large
contaminated spheres made of the different materials under study. Strikingly,
most of the hamsters developed classical clinical signs of prion disease and
typical disease-associated brain changes. Our findings suggest that prion
contamination of surfaces commonly present in the environment can be a source of
disease transmission, thus expanding our understanding of the mechanisms for
prion spreading in nature.
PMID- 29330305
TI - Restricted processing of CD16a/Fc gamma receptor IIIa N-glycans from primary
human NK cells impacts structure and function.
AB - CD16a/Fc gamma receptor IIIa is the most abundant antibody Fc receptor expressed
on human natural killer (NK) cells and activates a protective cytotoxic response
following engagement with antibody clustered on the surface of a pathogen or
diseased tissue. Therapeutic monoclonal antibodies (mAbs) with greater Fc
mediated affinity for CD16a show superior therapeutic outcome; however, one
significant factor that promotes antibody-CD16a interactions, the asparagine
linked carbohydrates (N-glycans), remains undefined. Here, we purified CD16a from
the primary NK cells of three donors and identified a large proportion of hybrid
(22%) and oligomannose N-glycans (23%). These proportions indicated restricted N
glycan processing and were unlike those of the recombinant CD16a forms, which
have predominantly complex-type N-glycans (82%). Tethering recombinant CD16a to
the membrane by including the transmembrane and intracellular domains and via
coexpression with the Fc epsilon receptor gamma-chain in HEK293F cells was
expected to produce N-glycoforms similar to NK cell-derived CD16a but yielded N
glycoforms different from NK cell-derived CD16a and recombinant soluble CD16a. Of
note, these differences in CD16a N-glycan composition affected antibody binding:
CD16a with oligomannose N-glycans bound IgG1 Fc with 12-fold greater affinity
than did CD16a having primarily complex-type and highly branched N-glycans. The
changes in binding activity mirrored changes in NMR spectra of the two CD16a
glycoforms, indicating that CD16a glycan composition also affects the
glycoprotein's structure. These results indicated that CD16a from primary human
NK cells is compositionally, and likely also functionally, distinct from commonly
used recombinant forms. Furthermore, our study provides critical evidence that
cell lineage determines CD16a N-glycan composition and antibody-binding affinity.
PMID- 29330306
TI - An Rb family-independent E2F3 transcription factor variant impairs STAT5
signaling and mammary gland remodeling during pregnancy in mice.
AB - E2F transcription factors are regulated by binding to the retinoblastoma (Rb)
tumor suppressor family of proteins. Previously, we reported an E2FLQ mutation
that disrupts the binding with Rb proteins without affecting the transcriptional
activity of E2F. We also showed that mouse embryonic fibroblasts with an E2F3LQ
mutation exhibit increased E2F activity and more rapid cell proliferation. In
this report, we analyzed E2F3LQ mice to further characterize the in vivo
consequences of Rb family-independent E2F3 activity. We found that homozygous
E2F3LQ mice were viable and had no obvious developmental defects or tumor growth.
Our results also indicated that E2F3LQ cells largely retain normal control of
cell proliferation in vivo However, female E2F3LQ mice had partial nursing
defects. Examination of the E2F3LQ mammary glands revealed increased caveolin-1
(CAV1) expression, reduced prolactin receptor/Stat5 signaling, and impaired
pregnancy-induced cell proliferation and differentiation. Of note, ChIP
experiments disclosed that E2F3 binds the CAV1 promoter. Furthermore, E2F3
overexpression induced CAV1 expression, and CRISPR/CAS9-mediated E2F3 knockout
reduced CAV1 levels and also increased prolactin receptor-induced Stat5 signaling
in mammary epithelial cells. Our results suggest that the Rb family-independent
E2F3 LQ variant inhibits pregnancy-induced mammary gland cell proliferation and
differentiation by up-regulating CAV1 expression and inhibiting Stat5 signaling.
PMID- 29330307
TI - Evidence suggests that germline RNF43 mutations are a rare cause of serrated
polyposis.
PMID- 29330308
TI - Survival outcomes of primary cutaneous T-cell lymphoma in HIV-infected patients:
a national population-based study.
AB - This study aimed to investigate clinical characteristics and survival outcomes of
primary cutaneous T-cell lymphoma (CTCL) in HIV-infected and non-HIV-infected
patients. All data were from the Surveillance, Epidemiology, and End Results
program, 1973-2013, of the U.S. National Cancer Institute. Data of 318 HIV
infected patients and 1272 non-HIV-infected patients with primary CTCL were
analyzed. Endpoints were overall survival and cancer-specific mortality.
Independent variables included demographics, pre-existing malignancy, treatments,
and environmental factors. Among 8823 patients with CTCL, 318 (3.60 per cent)
were HIV-infected and 8505 (96.40 per cent) were not. 318 HIV-infected patients
and 1272 non-HIV-infected patients selected by matching diagnosis dates were
analyzed, including 941 (59.2 per cent) males and 649 (40.8 per cent) females
with mean age 58.8 years. HIV-infected patients with CTCL had higher survival and
significantly lower risk of overall mortality than non-HIV-infected patients
(adjusted HR 0.37, 95 per cent CI 0.24 to 0.59, P<0.001). Non-HIV-infected, age
and black race were significant risk factors for overall mortality. Age and race
are independent risk factors for overall mortality in primary CTCL individuals,
and HIV-infected status is an independent protective factor, suggesting that
advanced antiretroviral therapy restores immunity and prolongs survival in HIV
infected patients with CTCL.
PMID- 29330309
TI - Poverty, a risk factor overlooked: a cross-sectional cohort study comparing
poverty rate and cardiovascular disease outcomes in the state of Florida.
AB - The purpose of this study is to examine the relationship between poverty rate and
heart disease in our state. A cross-sectional data analysis was performed using
figures provided by the Center for Disease Control's Interactive Atlas of Heart
Disease and Stroke Tables. Spearman's correlations and simple regressions were
used to determine if there was a relationship between poverty and cardiovascular
hospitalization rate and cardiovascular death rate. There was a positive
monotonic correlation between poverty rate and cardiovascular hospitalization
rate (Rho=0.384, P=0.001). There was a positive monotonic correlation between
poverty rate and cardiovascular death rate (Rho=0.646, P<0.0001). County poverty
rate had a statistically significant positive relationship with cardiovascular
hospitalization and cardiovascular mortality in the state of Florida.
PMID- 29330310
TI - Social determinants of community-level human papillomavirus vaccination coverage
in aschool-based vaccination programme.
AB - OBJECTIVE: To assess social patterns in human papillomavirus (HPV) vaccine
coverage in a school-based, government-funded vaccination programme located
within a single-payer universal healthcare system. DESIGN: We conducted a cross
sectional analysis of HPV vaccine uptake data for the 2013-2014 school year for
131 local authorities in England, and then evaluated the association between
vaccine uptake and socioeconomic status at the aggregate level. DATA SOURCES: HPV
vaccination coverage data from Public Health England's vaccine uptake guidance
and the UK's March 2011 Census. MAIN OUTCOME MEASURES: We measured three-dose
local authority-level vaccine series initiation to completion. RESULTS: We found
that in local authorities where there are more high-income families, the
vaccination rate is lower than in local authorities with more low-income
families. Local authorities with a higher percentage of whites, compared with non
whites, had higher HPV vaccination rates. Additionally, local authorities with
more non-migrants had higher rates of vaccination. Local authorities with more
education deprivation had higher rates of vaccination. Local authorities' higher
proportions of high-status occupations had worse vaccination coverage. In
bivariate analyses across all the socioeconomic indicators, a 1 SD change in the
indicators was associated with about a 2.25 percentage point decrease (for
income, education and occupation) or increase (for race and migrant composition)
in HPV dose coverage in the local authority. In multivariable analyses, only race
remained as a significant predictor of HPV coverage at the local authority level.
CONCLUSIONS: Across all three doses, there are notable variations by
socioeconomic status, with steep reverse gradients in three socioeconomic
indicators. More quantitative and qualitative research needs to be conducted to
determine the effects of the 2014 transition from a three-dose regimen to two
dose regimen on vaccination coverage, especially in groups that experience lower
rates of vaccination.
PMID- 29330311
TI - Necrosis in anti-SRP+ and anti-HMGCR+myopathies: Role of autoantibodies and
complement.
AB - OBJECTIVE: To characterize muscle fiber necrosis in immune-mediated necrotizing
myopathies (IMNM) with anti-signal recognition particle (SRP) or anti-3-hydroxy-3
methylglutarylcoenzyme A reductase (HMGCR) antibodies and to explore its
underlying molecular immune mechanisms. METHODS: Muscle biopsies from patients
with IMNM were analyzed and compared to biopsies from control patients with
myositis. In addition to immunostaining and reverse transcription PCR on muscle
samples, in vitro immunostaining on primary muscle cells was performed. RESULTS:
Creatine kinase levels and muscle regeneration correlated with the proportion of
necrotic fibers (r = 0.6, p < 0.001). CD68+iNOS+ macrophages and a Th-1 immune
environment were chiefly involved in ongoing myophagocytosis of necrotic fibers.
T-cell densities correlated with necrosis but no signs of cytotoxicity were
detected. Activation of the classical pathway of the complement cascade,
accompanied by deposition of sarcolemmal immunoglobulins, featured involvement of
humoral immunity. Presence of SRP and HMGCR proteins on altered myofibers was
reproduced on myotubes exposed to purified patient-derived autoantibodies.
Finally, a correlation between sarcolemmal complement deposits and fiber necrosis
was observed (r = 0.4 and p = 0.004). Based on these observations, we propose to
update the pathologic criteria of IMNM. CONCLUSION: These data further
corroborate the pathogenic role of anti-SRP and anti-HMGCR autoantibodies in
IMNM, highlighting humoral mechanisms as key players in immunity and myofiber
necrosis.
PMID- 29330313
TI - C-reactive protein and efficacy of antiplatelet therapy in (intracranial)
atherosclerosis.
PMID- 29330314
TI - Developmental Disability at School Age and Difficulty Obtaining Follow-up Data.
AB - BACKGROUND: The relationship of developmental disability rates with difficulty
obtaining follow-up data is unclear. With this study, we aimed to determine if
children who attended research follow-up assessments with more difficulty had
more disability at school age, compared with those who attended with less
difficulty, and to establish the relationship between follow-up and disability
rates. METHODS: Two groups, comprising 219 consecutive survivors born at <28
weeks' gestation or at <1000 g birth weight in the state of Victoria, Australia,
in 2005, and 218 term-born, normal birth weight controls were assessed at 8 years
of age for neurodevelopmental disability (any of IQ <-1 SD, cerebral palsy,
blindness, or deafness). Children were classified as either more or less
difficult to get to attend by research nurses involved in the study. RESULTS: The
follow-up rate was 87% for both groups. Overall, children who attended with more
difficulty had higher rates of neurodevelopmental disability (42%; 19 of 45) than
those who attended with less difficulty (20%; 66 of 328) (odds ratio: 3.09, 95%
confidence interval: 1.58 to 6.01; P = .001). As the follow-up rate rose among
the 3 individual hospitals involved in the assessments, so did the rate of
neurodevelopmental disability (P = .025). CONCLUSIONS: Children who attend with
more difficulty have higher rates of neurodevelopmental disability at school age
than those who attend with less difficulty, and disability rates rise with higher
follow-up rates. Rates of neurodevelopmental disability will be underestimated if
researchers are not persistent enough to obtain high follow-up rates.
PMID- 29330312
TI - High-sensitive C-reactive protein and dual antiplatelet in intracranial arterial
stenosis.
AB - OBJECTIVE: To determine the relationship of high-sensitive C-reactive protein
(hsCRP) and the efficacy and safety of dual antiplatelet therapy in patients with
and without intracranial arterial stenosis (ICAS) in the Clopidogrel in High-Risk
Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. METHODS:
A subgroup of 807 patients with both magnetic resonance angiography images and
hsCRP measurement was analyzed. Cox proportional hazards models were used to
assess the interaction of hsCRP levels with the effects of dual and single
antiplatelet therapy. RESULTS: A total of 358 (44.4%) patients had ICAS and 449
(55.6%) did not. The proportion of patients with elevated hsCRP levels was higher
in the ICAS group than in the non-ICAS group (40.2% vs 30.1%, p = 0.003). There
was significant interaction between hsCRP and the 2 antiplatelet therapy groups
in their effects on recurrent stroke after adjustment for confounding factors in
the patients with ICAS (p = 0.012), but not in those without (p = 0.256).
Compared with aspirin alone, clopidogrel plus aspirin significantly reduced the
risk of recurrent stroke only in the patients with ICAS and nonelevated hsCRP
levels (adjusted hazard ratio 0.27; 95% confidence interval 0.11 to 0.69; p =
0.006). Similar results were observed for composite vascular events. No
significant difference in bleeding was found. CONCLUSIONS: Presence of both ICAS
and nonelevated hsCRP levels may predict better response to dual antiplatelet
therapy in reducing new stroke and composite vascular events in minor stroke or
high-risk TIA patients. Further large-scale randomized and controlled clinical
trials are needed to confirm this finding.
PMID- 29330315
TI - Outcome of Preterm Infants With Postnatal Cytomegalovirus Infection.
AB - OBJECTIVES: To assess whether preterm infants with postnatal cytomegalovirus
infection develop neurologic sequelae in early childhood. METHODS: Infants <32
weeks' gestation were prospectively screened for cytomegalovirus (CMV) at term
equivalent age. Neurodevelopment was compared between CMV-positive and CMV
negative infants by using the Griffiths Mental Development Scales (GMDS) at 16
months' corrected age (CA); the Bayley Scales of Infant and Toddler Development,
Third Edition or the GMDS at 24 to 30 months' CA; and the Wechsler Preschool and
Primary Scale of Intelligence, Third Edition and Movement Assessment Battery for
Children, Second Edition at 6 years of age. At 6 years old, hearing was assessed
in CMV-positive children. RESULTS: Neurodevelopment was assessed in 356 infants
at 16 months' CA, of whom 49 (14%) were infected and 307 (86%) were noninfected.
Infected infants performed significantly better on the GMDS locomotor scale.
There were no differences at 24 to 30 months' CA on the Bayley Scales of Infant
and Toddler Development, Third Edition or GMDS. At 6 years of age, infected
children scored lower on the Wechsler Preschool and Primary Scale of
Intelligence, Third Edition, but mean scores were within normal range, reaching
significance only in verbal IQ (96 [SD 17] vs 103 [SD 15] points; P = .046).
Multiple regression indicated no impact of CMV status but significant influence
of maternal education and ethnicity on verbal IQ. No significant differences in
motor development were found and none of the infected children developed
sensorineural hearing loss. CONCLUSIONS: In this cohort study, postnatal
cytomegalovirus infection in preterm children did not have an adverse effect on
neurodevelopment within the first 6 years of life.
PMID- 29330316
TI - Myosin-1C uses a novel phosphoinositide-dependent pathway for nuclear
localization.
AB - Accurate control of macromolecule transport between nucleus and cytoplasm
underlines several essential biological processes, including gene expression.
According to the canonical model, nuclear import of soluble proteins is based on
nuclear localization signals and transport factors. We challenge this view by
showing that nuclear localization of the actin-dependent motor protein Myosin-1C
(Myo1C) resembles the diffusion-retention mechanism utilized by inner nuclear
membrane proteins. We show that Myo1C constantly shuttles in and out of the
nucleus and that its nuclear localization does not require soluble factors, but
is dependent on phosphoinositide binding. Nuclear import of Myo1C is preceded by
its interaction with the endoplasmic reticulum, and phosphoinositide binding is
specifically required for nuclear import, but not nuclear retention, of Myo1C.
Our results therefore demonstrate, for the first time, that membrane association
and binding to nuclear partners is sufficient to drive nuclear localization of
also soluble proteins, opening new perspectives to evolution of cellular protein
sorting mechanisms.
PMID- 29330317
TI - tRNA production links nutrient conditions to the onset of sexual differentiation
through the TORC1 pathway.
AB - Target of rapamycin (TOR) kinase controls cell growth and metabolism in response
to nutrient availability. In the fission yeast Schizosaccharomyces pombe, TOR
complex 1 (TORC1) promotes vegetative growth and inhibits sexual differentiation
in the presence of ample nutrients. Here, we report the isolation and
characterization of mutants with similar phenotypes as TORC1 mutants, in that
they initiate sexual differentiation even in nutrient-rich conditions. In most
mutants identified, TORC1 activity is downregulated and the mutated genes are
involved in tRNA expression or modification. Expression of tRNA precursors
decreases when cells undergo sexual differentiation. Furthermore, overexpression
of tRNA precursors prevents TORC1 downregulation upon nitrogen starvation and
represses the initiation of sexual differentiation. Based on these observations,
we propose that tRNA precursors operate in the S. pombe TORC1 pathway to switch
growth mode from vegetative to reproductive.
PMID- 29330318
TI - Shifting meiotic to mitotic spindle assembly in oocytes disrupts chromosome
alignment.
AB - Mitotic spindles assemble from two centrosomes, which are major microtubule
organizing centers (MTOCs) that contain centrioles. Meiotic spindles in oocytes,
however, lack centrioles. In mouse oocytes, spindle microtubules are nucleated
from multiple acentriolar MTOCs that are sorted and clustered prior to completion
of spindle assembly in an "inside-out" mechanism, ending with establishment of
the poles. We used HSET (kinesin-14) as a tool to shift meiotic spindle assembly
toward a mitotic "outside-in" mode and analyzed the consequences on the fidelity
of the division. We show that HSET levels must be tightly gated in meiosis I and
that even slight overexpression of HSET forces spindle morphogenesis to become
more mitotic-like: rapid spindle bipolarization and pole assembly coupled with
focused poles. The unusual length of meiosis I is not sufficient to correct these
early spindle morphogenesis defects, resulting in severe chromosome alignment
abnormalities. Thus, the unique "inside-out" mechanism of meiotic spindle
assembly is essential to prevent chromosomal misalignment and production of
aneuploidy gametes.
PMID- 29330319
TI - Correction: A Plant-Derived Nucleic Acid Reconciles Type I IFN and a Pyroptotic
like Event in Immunity against Respiratory Viruses.
PMID- 29330320
TI - Cutting Edge: Homeostasis of Innate Lymphoid Cells Is Imbalanced in Psoriatic
Arthritis.
AB - Innate lymphoid cells (ILC) have a high potency for cytokine production
independent of specific Ag stimulation. Imbalance of ILC subsets may influence
cytokine production in humans and hence be associated with the development of
inflammatory disease. Evidence for an imbalance of ILC homeostasis in human
disease, however, is very limited to date. In this study we show that psoriatic
arthritis (PsA), a severe disease of the joints depending on the activation of
the IL-23/IL-17 pathway, is characterized by a skewed ILC homeostasis.
Circulating ILC3s as potent source of IL-17/IL-22 were elevated in active PsA,
whereas ILC2s, which produce proresolving cytokines, were decreased. The
ILC2/ILC3 ratio was significantly correlated with clinical disease activity
scores and the presence of imaging signs of joint inflammation and bone damage.
Multivariable analysis showed that a high ILC2/ILC3 ratio is associated with
remission in PsA, suggesting that specific alterations of ILC homeostasis control
disease activity in PsA.
PMID- 29330321
TI - Osteopontin Promotes Protective Antigenic Tolerance against Experimental Allergic
Airway Disease.
AB - In the context of inflammation, osteopontin (Opn) is known to promote effector
responses, facilitating a proinflammatory environment; however, its role during
antigenic tolerance induction is unknown. Using a mouse model of asthma, we
investigated the role of Opn during antigenic tolerance induction and its effects
on associated regulatory cellular populations prior to disease initiation. Our
experiments demonstrate that Opn drives protective antigenic tolerance by
inducing accumulation of IFN-beta-producing plasmacytoid dendritic cells, as well
as regulatory T cells, in mediastinal lymph nodes. We also show that, in the
absence of TLR triggers, recombinant Opn, and particularly its SLAYGLR motif,
directly induces IFN-beta expression in Ag-primed plasmacytoid dendritic cells,
which renders them extra protective against induction of allergic airway disease
upon transfer into recipient mice. Lastly, we show that blockade of type I IFNR
prevents antigenic tolerance induction against experimental allergic asthma.
Overall, we unveil a new role for Opn in setting up a tolerogenic milieu boosting
antigenic tolerance induction, thus leading to prevention of allergic airway
inflammation. Our results provide insight for the future design of
immunotherapies against allergic asthma.
PMID- 29330322
TI - Cutting Edge: Piezo1 Mechanosensors Optimize Human T Cell Activation.
AB - TCRs recognize peptides on MHC molecules and induce downstream signaling, leading
to activation and clonal expansion. In addition to the strength of the
interaction of TCRs with peptides on MHC molecules, mechanical forces contribute
to optimal T cell activation, as reflected by the superior efficiency of
immobilized TCR-cross-linking Abs compared with soluble Abs in TCR triggering,
although a dedicated mechanotransduction module is not identified. We found that
the professional mechanosensor protein Piezo1 is critically involved in human T
cell activation. Although a deficiency in Piezo1 attenuates downstream events on
ex vivo TCR triggering, a Piezo1 agonist can obviate the need to immobilize TCR
cross-linking Abs. Piezo1-driven Ca2+ influx, leading to calpain activation and
organization of cortical actin scaffold, links this mechanosensor to optimal TCR
signaling. Thus, we discovered a hitherto unknown regulatory mechanism for human
T cell activation and provide the first evidence, to our knowledge, for the
involvement of Piezo1 mechanosensors in immune regulation.
PMID- 29330324
TI - Betaine Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibiting
Dendritic Cell-Derived IL-6 Production and Th17 Differentiation.
AB - IL-17-secreting T cells (Th17 cells) play a pathogenic role in multiple
autoimmune diseases, including multiple sclerosis (MS), and dendritic cell (DC)
derived cytokines play pivotal roles in promoting the differentiation of naive
CD4+ T cells into Th cell subsets (Th1 and Th17). Therefore, small molecules
blocking the key cytokines produced by DCs will be beneficial in MS. In this
article, we report that betaine treatment ameliorates MS pathogenesis by
inhibiting DC-derived IL-6 production and Th17 differentiation. Using
experimental autoimmune encephalomyelitis, a widely used mouse model of MS, we
found that, compared with the vehicle-treated group, betaine-treated mice
exhibited less severe experimental autoimmune encephalomyelitis symptoms,
including lower clinical scores, reduced leukocyte infiltration, and less
extensive demyelination in the CNS. Moreover, a significantly lower percentage of
Th17 cells, one of the major pathogenic effector cells in MS progression, was
observed in the peripheral immune system and in the CNS. Interestingly, in the in
vitro Th17-differentiation assay, no significant change in Th17 cells was
observed between the vehicle- and betaine-treated groups, whereas in the in vitro
DC culture experiment, betaine treatment significantly decreased DC-derived IL-6
production. In the DC-T cell coculture experiment, a significantly decreased Th17
differentiation was observed upon betaine treatment. All of these data
demonstrated that betaine inhibited Th17 differentiation indirectly by reducing
IL-6 production by DCs. In brief, our findings demonstrated the pivotal roles of
betaine in modulating MS pathogenesis and suggested that it may serve as a
potential novel drug candidate for the treatment of MS.
PMID- 29330323
TI - IL-10 Deficiency Reveals a Role for TLR2-Dependent Bystander Activation of T
Cells in Lyme Arthritis.
AB - T cells predominate the immune responses in the synovial fluid of patients with
persistent Lyme arthritis; however, their role in Lyme disease remains poorly
defined. Using a murine model of persistent Lyme arthritis, we observed that
bystander activation of CD4+ and CD8+ T cells leads to arthritis-promoting IFN
gamma, similar to the inflammatory environment seen in the synovial tissue of
patients with posttreatment Lyme disease. TCR transgenic mice containing
monoclonal specificity toward non-Borrelia epitopes confirmed that bystander T
cell activation was responsible for disease development. The microbial pattern
recognition receptor TLR2 was upregulated on T cells following infection,
implicating it as marker of bystander T cell activation. In fact, T cell
intrinsic expression of TLR2 contributed to IFN-gamma production and arthritis,
providing a mechanism for microbial-induced bystander T cell activation during
infection. The IL-10-deficient mouse reveals a novel TLR2-intrinsic role for T
cells in Lyme arthritis, with potentially broad application to immune
pathogenesis.
PMID- 29330325
TI - Cutting Edge: Plasmodium falciparum Induces Trained Innate Immunity.
AB - Malarial infection in naive individuals induces a robust innate immune response.
In the recently described model of innate immune memory, an initial stimulus
primes the innate immune system to either hyperrespond (termed training) or
hyporespond (tolerance) to subsequent immune challenge. Previous work in both
mice and humans demonstrated that infection with malaria can both serve as a
priming stimulus and promote tolerance to subsequent infection. In this study, we
demonstrate that initial stimulation with Plasmodium falciparum-infected RBCs or
the malaria crystal hemozoin induced human adherent PBMCs to hyperrespond to
subsequent ligation of TLR2. This hyperresponsiveness correlated with increased
H3K4me3 at important immunometabolic promoters, and these epigenetic
modifications were also seen in Kenyan children naturally infected with malaria.
However, the use of epigenetic and metabolic inhibitors indicated that the
induction of trained immunity by malaria and its ligands may occur via a
previously unrecognized mechanism(s).
PMID- 29330326
TI - Loss of Balance between Striatal Feedforward Inhibition and Corticostriatal
Excitation Leads to Tremor.
AB - Fast-spiking interneurons (FSIs) exert powerful inhibitory control over the
striatum and are hypothesized to balance the massive excitatory cortical and
thalamic input to this structure. We recorded neuronal activity in the
dorsolateral striatum and globus pallidus (GP) concurrently with the detailed
movement kinematics of freely behaving female rats before and after selective
inhibition of FSI activity using IEM-1460 microinjections. The inhibition led to
the appearance of episodic rest tremor in the body part that depended on the
somatotopic location of the injection within the striatum. The tremor was
accompanied by coherent oscillations in the local field potential (LFP).
Individual neuron activity patterns became oscillatory and coherent in the tremor
frequency. Striatal neurons, but not GP neurons, displayed additional temporal,
nonoscillatory correlations. The subsequent reduction in the corticostriatal
input following muscimol injection to the corresponding somatotopic location in
the primary motor cortex led to disruption of the tremor and a reduction of the
LFP oscillations and individual neuron's phase-locked activity. The breakdown of
the normal balance of excitation and inhibition in the striatum has been shown
previously to be related to different motor abnormalities. Our results further
indicate that the balance between excitatory corticostriatal input and
feedforward FSI inhibition is sufficient to break down the striatal decorrelation
process and generate oscillations resulting in rest tremor typical of multiple
basal ganglia disorders.SIGNIFICANCE STATEMENT Fast-spiking interneurons (FSIs)
play a key role in normal striatal processing by exerting powerful inhibitory
control over the network. FSI malfunctions have been associated with abnormal
processing of information within the striatum that leads to multiple movement
disorders. Here, we study the changes in neuronal activity and movement
kinematics following selective inhibition of these neurons. The injections led to
the appearance of episodic rest tremor, accompanied by coherent oscillations in
neuronal activity, which was reversed following corticostriatal inhibition. These
results suggest that the balance between corticostriatal excitation and
feedforward FSI inhibition is crucial for maintaining the striatal decorrelation
process, and that its breakdown leads to the formation of oscillations resulting
in rest tremor typical of multiple basal ganglia disorders.
PMID- 29330327
TI - Signal Complexity of Human Intracranial EEG Tracks Successful Associative-Memory
Formation across Individuals.
AB - Memory performance is highly variable among individuals. Most studies examining
human memory, however, have largely focused on the neural correlates of
successful memory formation within individuals, rather than the differences among
them. As such, what gives rise to this variability is poorly understood. Here, we
examined intracranial EEG (iEEG) recordings captured from 43 participants (23
male) implanted with subdural electrodes for seizure monitoring as they performed
a paired-associates verbal memory task. We identified three separate but related
signatures of neural activity that tracked differences in successful memory
formation across individuals. High-performing individuals consistently exhibited
less broadband power, flatter power spectral density slopes, and greater
complexity in their iEEG signals. Furthermore, within individuals across three
separate time scales ranging from seconds to days, successful recall was
positively associated with these same metrics. Our data therefore suggest that
memory ability across individuals can be indexed by increased neural signal
complexity.SIGNIFICANCE STATEMENT We show that participants whose intracranial
EEG exhibits less low-frequency power, flatter power spectrums, and greater
sample entropy overall are better able to memorize associations, and that the
same metrics track fluctuations in memory performance across time within
individuals. These metrics together signify greater neural signal complexity,
which may index the brain's ability to flexibly engage with information and
generate separable memory representations. Critically, the current set of results
provides a unique window into the neural markers of individual differences in
memory performance, which have hitherto been underexplored.
PMID- 29330328
TI - Assembling a Cellular User Manual for the Brain.
AB - For many years, efforts to decipher the various cellular components that comprise
the CNS were stymied by a lack of technical strategies for isolating and
profiling the brain's resident cell types. The advent of transcriptional
profiling, combined with powerful new purification schemes, changed this reality
and transformed our understanding of the macroglial populations within the brain.
Here, we chronicle the historical context and scientific setting for our efforts
to transcriptionally profile neurons, astrocytes, and oligodendrocytes, and
highlight some of the profound discoveries that were cultivated by these
data.Following a lengthy battle with pancreatic cancer, Ben Barres passed away
during the writing of this Progression piece. Among Ben's innumerable
contributions to the greater scientific community, his addition of publicly
available transcriptome databases of CNS cell types will forever remain a relic
of his generous spirit and boundless scientific curiosity. Although he had
impressively committed a majority of these enormous gene lists to memory, Ben
could oftentimes be spotted at meetings buried in his cell phone on the Barres
RNAseq database. Perhaps the only thing he enjoyed more than exploring these data
himself, was knowing how useful these contributions had been (and will hopefully
continue to be) to his scientific peers.
PMID- 29330329
TI - Large genomic insertion at the Shh locus results in hammer toes through enhancer
adoption.
PMID- 29330330
TI - Greening up the mountain.
PMID- 29330331
TI - Molecular pathways to nonbiting mosquitoes.
PMID- 29330332
TI - Identification and Characterization of Sites Where Persistent Atrial Fibrillation
Is Terminated by Localized Ablation.
AB - BACKGROUND: The mechanisms by which persistent atrial fibrillation (AF)
terminates via localized ablation are not well understood. To address the
hypothesis that sites where localized ablation terminates persistent AF have
characteristics identifiable with activation mapping during AF, we systematically
examined activation patterns acquired only in cases of unequivocal termination by
ablation. METHODS AND RESULTS: We recruited 57 patients with persistent AF
undergoing ablation, in whom localized ablation terminated AF to sinus rhythm or
organized tachycardia. For each site, we performed an offline analysis of
unprocessed unipolar electrograms collected during AF from multipolar basket
catheters using the maximum -dV/dt assignment to construct isochronal activation
maps for multiple cycles. Additional computational modeling and phase analysis
were used to study mechanisms of map variability. At all sites of AF termination,
localized repetitive activation patterns were observed. Partial rotational
circuits were observed in 26 of 57 (46%) cases, focal patterns in 19 of 57 (33%),
and complete rotational activity in 12 of 57 (21%) cases. In computer
simulations, incomplete segments of partial rotations coincided with areas of
slow conduction characterized by complex, multicomponent electrograms, and
variations in assigning activation times at such sites substantially altered
mapped mechanisms. CONCLUSIONS: Local activation mapping at sites of termination
of persistent AF showed repetitive patterns of rotational or focal activity. In
computer simulations, complete rotational activation sequence was observed but
was sensitive to assignment of activation timing particularly in segments of slow
conduction. The observed phenomena of repetitive localized activation and the
mechanism by which local ablation terminates putative AF drivers require further
investigation.
PMID- 29330333
TI - Standard Ablation Versus Magnetic Resonance Imaging-Guided Ablation in the
Treatment of Ventricular Tachycardia.
PMID- 29330334
TI - Detection of heterozygous mutation in hook microtubule-tethering protein 1 in
three patients with decapitated and decaudated spermatozoa syndrome.
AB - BACKGROUND: The mechanism of intramanchette transport is crucial to the
transformation of sperm tail and the nuclear condensation during spermiogenesis.
Although few dysfunctional proteins could result in abnormal junction between the
head and tail of spermatozoon, little is known about the genetic cues in this
process. OBJECTIVE: Based on patients with severe decapitated and decaudated
spermatozoa (DDS) syndrome, the study aimed to validate whether new mutation
exists on their Hook microtubule-tethering protein 1 (HOOK1) genes and follow
their results of assisted reproduction treatment (ART). METHODS: 7 severe
teratozoospermia patients with DDS (proportion >95%) and three relative members
in one pedigree were collected to sequence the whole genomic DNA. The
fertilisation rates (FRs) of these patients were followed. Morphological
observation and interspecies intracytoplasmic sperm injection (ICSI) assays were
applied. RESULTS: A novel missense mutation of A to G (p.Q286R) in patients with
DDS (n=3/7) was found in the HOOK1 gene, which was inherited from the mother in
one patient. This variant was absent in 160 fertile population-matched control
individuals. Morphological observation showed that almost all the DDS broke into
decaudated heads and headless tails at the implantation fossa or the basal plate.
The clinical studies indicated that the mutation might cause reduced FRs on both
ART (FR=18.07%) and interspecies ICSI (FR=16.98%). CONCLUSIONS: An unreported
mutation in HOOK1 gene was identified, which might be responsible to some
patients with DDS. Further studies need to uncover the molecular mechanism of
spermiogenesis for genomic therapy.
PMID- 29330335
TI - Fabry Disease: prevalence of affected males and heterozygotes with pathogenic GLA
mutations identified by screening renal, cardiac and stroke clinics, 1995-2017.
AB - BACKGROUND: Fabry Disease (FD), an X linked lysosomal storage disease due to
pathogenic alpha-galactosidase A (GLA) mutations, results in two major subtypes,
the early-onset Type 1 'Classic' and the Type 2 'Later-Onset' phenotypes. To
identify previously unrecognised patients, investigators screened cardiac, renal
and stroke clinics by enzyme assays. However, some screening studies did not
perform confirmatory GLA mutation analyses, and many included recently recognised
'benign/likely-benign' variants, thereby inflating prevalence estimates. METHODS:
Online databases were searched for all FD screening studies in high-risk clinics
(1995-2017). Studies reporting GLA mutations were re-analysed for pathogenic
mutations, sex and phenotype. Phenotype-specific and sex-specific prevalence
rates were determined. RESULTS: Of 67 studies, 63 that screened 51363patients
(33943M and 17420F) and provided GLA mutations were reanalysed for disease
causing mutations. Of reported GLA mutations, benign variants occurred in 47.9%
of males and 74.1% of females. The following were the revised prevalence
estimates: among 36820 (23954M and 12866F) haemodialysis screenees, 0.21% males
and 0.15% females; among 3074 (2031M and 1043F) renal transplant screenees, 0.25%
males and no females; among 5491 (4054M and 1437F) cardiac screenees, 0.94% males
and 0.90% females; and among 5978 (3904M and 2074F) stroke screenees, 0.13% males
and 0.14% females. Among male and female screenees with pathogenic mutations, the
type 1 Classic phenotype was predominant (~60%), except more male cardiac
patients (75%) had type 2 Later-Onset phenotype. CONCLUSIONS: Compared with
previous findings, reanalysis of 63 studies increased the screenee numbers (~3.4
fold), eliminated 20 benign/likely benign variants, and provided more accurate
sex-specific and phenotype-specific prevalence estimates, ranging from ~0.13% of
stroke to ~0.9% of cardiac male or female screenees.
PMID- 29330336
TI - Risk factors for survival in patients with von Hippel-Lindau disease.
AB - BACKGROUND: Historically, von Hippel-Lindau (VHL) disease is characterised by a
poor survival. Although genotype-phenotype correlation has been described in many
studies, the risk factors for VHL survival remain unclear. This study aims to
evaluate the median survival of Chinese patients with VHL disease and explore
whether VHL survival is influenced by genetic and clinical factors. METHODS: In
this retrospective study, we recruited 340 patients from 127 VHL families. Kaplan
Meier plot and Cox regression model were used to evaluate the median survival and
assess how survival was influenced by birth year, birth order, sex, family
history, mutation type, onset age and first presenting symptom. RESULTS: The
estimated median life expectancy for Chinese patients with VHL disease was 62
years. Patients with early-onset age, positive family history and truncating
mutation types had poorer overall and VHL-related survival. Patients with
haemangioblastoma as their first presenting symptom were related to a higher risk
of death from central nervous system haemangioblastoma than those with abdominal
lesions (HR 8.84, 95% CI 2.04 to 38.37, P=0.004). CONCLUSIONS: This largest VHL
survival analysis indicates that onset age, family history, mutation type and
first presenting symptom have an effect on the survival of patients with VHL
disease, which is helpful to genetic counselling and clinical decision-making.
PMID- 29330337
TI - Role of germline aberrations affecting CTNNA1, MAP3K6 and MYD88 in gastric cancer
susceptibility.
AB - BACKGROUND: In approximately 10% of all gastric cancer (GC) cases, a heritable
cause is suspected. A subset of these cases have a causative germline CDH1
mutation; however, in most cases the cause remains unknown. Our objective was to
assess to what extent these remaining cases may be explained by germline
mutations in the novel candidate GC predisposing genes CTNNA1, MAP3K6 or MYD88.
METHODS: We sequenced a large cohort of unexplained young and/or familial
patients with GC (n=286) without a CDH1germline mutation for germline variants
affecting CTNNA1, MAP3K6 and MYD88 using a targeted next-generation sequencing
approach based on single-molecule molecular inversion probes. RESULTS: Predicted
deleterious germline variants were not encountered in MYD88, but recurrently
observed in CTNNA1 (n=2) and MAP3K6 (n=3) in our cohort of patients with GC. In
contrast to deleterious variants in CTNNA1, deleterious variants in MAP3K6 also
occur frequently in the general population. CONCLUSIONS: Based on our results
MAP3K6 should no longer be considered a GC predisposition gene, whereas
deleterious CTNNA1 variants are confirmed as an infrequent cause of GC
susceptibility. Biallelic MYD88 germline mutations are at most a very rare cause
of GC susceptibility as no additional cases were identified.
PMID- 29330339
TI - HIV-Positive Kidney Donor Selection for HIV-Positive Transplant Recipients.
AB - The risks associated with transplanting HIV-positive kidneys into HIV-positive
recipients have not been well studied. Since 2008, 43 kidneys from 25 HIV
positive deceased donors have been transplanted into patients who are HIV
positive in Cape Town, South Africa. Among the donors, 19 (76%) died secondary to
trauma. The average age for donors was 34 (interquartile range, 19-52) years old.
In some donors, only one kidney was used because of a limited number of suitable
recipients on the waiting list. Only two donors had been previously exposed to
antiretroviral triple therapy. In 23 of the deceased organ donors, the HIV status
was not known before the time of death. Initial concerns about transplanting HIV
positive allografts into HIV-positive recipients in this clinic revolved around
the possibility of HIV superinfection. However, all recipients remained virally
suppressed several years after the transplant. Only one recipient experienced an
increased viral load after the transplant, which was related to a period of
noncompliance on her medication. After counseling and improved compliance, the
viral load decreased and became suppressed again. Herein, we discuss the findings
of this study and review the literature available on this crucial topic.
PMID- 29330338
TI - Diagnosis, management, histology and genetics of sporadic primary
hyperparathyroidism: old knowledge with new tricks.
AB - Primary hyperparathyroidism (pHPT) is a common endocrinopathy resulting from
inappropriately high PTH secretion. It usually results from the presence of a
single gland adenoma, multiple gland hyperplasia or rarely parathyroid carcinoma.
All these conditions require different management, and it is important to be able
to differentiate the underlined pathology, in order for the clinicians to provide
the best therapeutic approach. Elucidation of the genetic background of each of
these clinical entities would be of great interest. However, the molecular
factors that control parathyroid tumorigenesis are poorly understood. There are
data implicating the existence of specific genetic pathways involved in the
emergence of parathyroid tumorigenesis. The main focus of the present study is to
present the current optimal diagnostic and management protocols for pHPT as well
as to review the literature regarding all molecular and genetic pathways that are
to be involved in the pathophysiology of sporadic pHPT.
PMID- 29330340
TI - The Adiponectin Receptor Agonist AdipoRon Ameliorates Diabetic Nephropathy in a
Model of Type 2 Diabetes.
AB - Adiponectin exerts renoprotective effects against diabetic nephropathy (DN) by
activating the AMP-activated protein kinase (AMPK)/peroxisome proliferative
activated receptor-alpha (PPARalpha) pathway through adiponectin receptors
(AdipoRs). AdipoRon is an orally active synthetic adiponectin receptor agonist.
We investigated the expression of AdipoRs and the associated intracellular
pathways in 27 patients with type 2 diabetes and examined the effects of AdipoRon
on DN development in male C57BLKS/J db/db mice, glomerular endothelial cells
(GECs), and podocytes. The extent of glomerulosclerosis and tubulointerstitial
fibrosis correlated with renal function deterioration in human kidneys.
Expression of AdipoR1, AdipoR2, and Ca2+/calmodulin-dependent protein kinase
kinase-beta (CaMKKbeta) and numbers of phosphorylated liver kinase B1 (LKB1)- and
AMPK-positive cells significantly decreased in the glomeruli of early stage human
DN. AdipoRon treatment restored diabetes-induced renal alterations in db/db mice.
AdipoRon exerted renoprotective effects by directly activating intrarenal AdipoR1
and AdipoR2, which increased CaMKKbeta, phosphorylated Ser431LKB1, phosphorylated
Thr172AMPK, and PPARalpha expression independently of the systemic effects of
adiponectin. AdipoRon-induced improvement in diabetes-induced oxidative stress
and inhibition of apoptosis in the kidneys ameliorated relevant intracellular
pathways associated with lipid accumulation and endothelial dysfunction. In high
glucose-treated human GECs and murine podocytes, AdipoRon increased intracellular
Ca2+ levels that activated a CaMKKbeta/phosphorylated Ser431LKB1/phosphorylated
Thr172AMPK/PPARalpha pathway and downstream signaling, thus decreasing high
glucose-induced oxidative stress and apoptosis and improving endothelial
dysfunction. AdipoRon further produced cardioprotective effects through the same
pathway demonstrated in the kidney. Our results show that AdipoRon ameliorates
GEC and podocyte injury by activating the intracellular Ca2+/LKB1-AMPK/PPARalpha
pathway, suggesting its efficacy for treating type 2 diabetes-associated DN.
PMID- 29330341
TI - Biomechanics of coupled motion in the cervical spine during simulated whiplash in
patients with pre-existing cervical or lumbar spinal fusion: A Finite Element
Study.
AB - OBJECTIVES: Loss of motion following spine segment fusion results in increased
strain in the adjacent motion segments. However, to date, studies on the
biomechanics of the cervical spine have not assessed the role of coupled motions
in the lumbar spine. Accordingly, we investigated the biomechanics of the
cervical spine following cervical fusion and lumbar fusion during simulated
whiplash using a whole-human finite element (FE) model to simulate coupled
motions of the spine. METHODS: A previously validated FE model of the human body
in the driver-occupant position was used to investigate cervical hyperextension
injury. The cervical spine was subjected to simulated whiplash exposure in
accordance with Euro NCAP (the European New Car Assessment Programme) testing
using the whole human FE model. The coupled motions between the cervical spine
and lumbar spine were assessed by evaluating the biomechanical effects of
simulated cervical fusion and lumbar fusion. RESULTS: Peak anterior longitudinal
ligament (ALL) strain ranged from 0.106 to 0.382 in a normal spine, and from
0.116 to 0.399 in a fused cervical spine. Strain increased from cranial to caudal
levels. The mean strain increase in the motion segment immediately adjacent to
the site of fusion from C2-C3 through C5-C6 was 26.1% and 50.8% following single-
and two-level cervical fusion, respectively (p = 0.03, unpaired two-way t-test).
Peak cervical strains following various lumbar-fusion procedures were 1.0% less
than those seen in a healthy spine (p = 0.61, two-way ANOVA). CONCLUSION:
Cervical arthrodesis increases peak ALL strain in the adjacent motion segments.
C3-4 experiences greater changes in strain than C6-7. Lumbar fusion did not have
a significant effect on cervical spine strain.Cite this article: H. Huang, R. W.
Nightingale, A. B. C. Dang. Biomechanics of coupled motion in the cervical spine
during simulated whiplash in patients with pre-existing cervical or lumbar spinal
fusion: A Finite Element Study. Bone Joint Res 2018;7:28-35. DOI: 10.1302/2046
3758.71.BJR-2017-0100.R1.
PMID- 29330342
TI - Are the patient-rated wrist evaluation (PRWE) and the disabilities of the arm,
shoulder and hand (DASH) questionnaire used in distal radial fractures truly
valid and reliable?
AB - OBJECTIVES: The patient-rated wrist evaluation (PRWE) and the Disabilities of the
Arm, Shoulder and Hand (DASH) questionnaire are patient-reported outcome measures
(PROMs) used for clinical and research purposes. Methodological high-quality
clinimetric studies that determine the measurement properties of these PROMs when
used in patients with a distal radial fracture are lacking. This study aimed to
validate the PRWE and DASH in Dutch patients with a displaced distal radial
fracture (DRF). METHODS: The intraclass correlation coefficient (ICC) was used
for test-retest reliability, between PROMs completed twice with a two-week
interval at six to eight months after DRF. Internal consistency was determined
using Cronbach's alpha for the dimensions found in the factor analysis. The
measurement error was expressed by the smallest detectable change (SDC). A semi
structured interview was conducted between eight and 12 weeks after DRF to assess
the content validity. RESULTS: A total of 119 patients (mean age 58 years (sd
15)), 74% female, completed PROMs at a mean time of six months (sd 1) post
fracture. One overall meaningful dimension was found for the PRWE and the DASH.
Internal consistency was excellent for both PROMs (Cronbach's alpha 0.96 (PRWE)
and 0.97 (DASH)). Test-retest reliability was good for the PRWE (ICC 0.87) and
excellent for the DASH (ICC 0.91). The SDC was 20 for the PRWE and 14 for the
DASH. No floor or ceiling effects were found. The content validity was good for
both questionnaires. CONCLUSION: The PRWE and DASH are valid and reliable PROMs
in assessing function and disability in Dutch patients with a displaced DRF.
However, due to the high SDC, the PRWE and DASH are less useful for individual
patients with a distal radial fracture in clinical practice.Cite this article: Y.
V. Kleinlugtenbelt, R. G. Krol, M. Bhandari, J. C. Goslings, R. W. Poolman, V. A.
B. Scholtes. Are the patient-rated wrist evaluation (PRWE) and the disabilities
of the arm, shoulder and hand (DASH) questionnaire used in distal radial
fractures truly valid and reliable? Bone Joint Res 2018;7:36-45. DOI:
10.1302/2046-3758.71.BJR-2017-0081.R1.
PMID- 29330343
TI - Treatment of osteomyelitis defects by a vancomycin-loaded gelatin/beta-tricalcium
phosphate composite scaffold.
AB - OBJECTIVE: In the present study, we aimed to assess whether gelatin/beta
tricalcium phosphate (beta-TCP) composite porous scaffolds could be used as a
local controlled release system for vancomycin. We also investigated the
efficiency of the scaffolds in eliminating infections and repairing osteomyelitis
defects in rabbits. METHODS: The gelatin scaffolds containing differing amounts
of of beta-TCP (0%, 10%, 30% and 50%) were prepared for controlled release of
vancomycin and were labelled G-TCP0, G-TCP1, G-TCP3 and G-TCP5, respectively. The
Kirby-Bauer method was used to examine the release profile. Chronic osteomyelitis
models of rabbits were established. After thorough debridement, the osteomyelitis
defects were implanted with the scaffolds. Radiographs and histological
examinations were carried out to investigate the efficiency of eliminating
infections and repairing bone defects. RESULTS: The prepared gelatin/beta-TCP
scaffolds exhibited a homogeneously interconnected 3D porous structure. The G
TCP0 scaffold exhibited the longest duration of vancomycin release with a release
duration of eight weeks. With the increase of beta-TCP contents, the release
duration of the beta-TCP-containing composite scaffolds was decreased. The
complete release of vancomycin from the G-TCP5 scaffold was achieved within three
weeks. In the treatment of osteomyelitis defects in rabbits, the G-TCP3 scaffold
showed the most efficacious performance in eliminating infections and repairing
bone defects. CONCLUSIONS: The composite scaffolds could achieve local
therapeutic drug levels over an extended duration. The G-TCP3 scaffold possessed
the optimal porosity, interconnection and controlled release performance.
Therefore, this scaffold could potentially be used in the treatment of chronic
osteomyelitis defects.Cite this article: J. Zhou, X. G. Zhou, J. W. Wang, H.
Zhou, J. Dong. Treatment of osteomyelitis defects by a vancomycin-loaded
gelatin/beta-tricalcium phosphate composite scaffold. Bone Joint Res 2018;7:46
57. DOI: 10.1302/2046-3758.71.BJR-2017-0129.R2.
PMID- 29330344
TI - Parathyroid hormone-related protein exhibits antioxidant features in osteoblastic
cells through its N-terminal and osteostatin domains.
AB - OBJECTIVES: Oxidative stress plays a major role in the onset and progression of
involutional osteoporosis. However, classical antioxidants fail to restore
osteoblast function. Interestingly, the bone anabolism of parathyroid hormone
(PTH) has been shown to be associated with its ability to counteract oxidative
stress in osteoblasts. The PTH counterpart in bone, which is the PTH-related
protein (PTHrP), displays osteogenic actions through both its N-terminal PTH-like
region and the C-terminal domain. METHODS: We examined and compared the
antioxidant capacity of PTHrP (1-37) with the C-terminal PTHrP domain comprising
the 107-111 epitope (osteostatin) in both murine osteoblastic MC3T3-E1 cells and
primary human osteoblastic cells. RESULTS: We showed that both N- and C-terminal
PTHrP peptides at 100 nM decreased reactive oxygen species production and
forkhead box protein O activation following hydrogen peroxide (H2O2)-induced
oxidation, which was related to decreased lipid oxidative damage and caspase-3
activation in these cells. This was associated with their ability to restore the
deleterious effects of H2O2 on cell growth and alkaline phosphatase activity, as
well as on the expression of various osteoblast differentiation genes. The
addition of Rp-cyclic 3',5'-hydrogen phosphorothioate adenosine triethylammonium
salt (a cyclic 3',5'-adenosine monophosphate antagonist) and calphostin C (a
protein kinase C inhibitor), or a PTH type 1 receptor antagonist, abrogated the
effects of N-terminal PTHrP, whereas protein phosphatase 1 (an Src kinase
activity inhibitor), SU1498 (a vascular endothelial growth factor receptor 2
inhibitor), or an anti osteostatin antiserum, inhibited the effects of C-terminal
PTHrP. CONCLUSION: These findings indicate that the antioxidant properties of
PTHrP act through its N- and C-terminal domains and provide novel insights into
the osteogenic action of PTHrP.Cite this article: S. Portal-Nunez, J. A. Ardura,
D. Lozano, I. Martinez de Toda, M. De la Fuente, G. Herrero-Beaumont, R. Largo,
P. Esbrit. Parathyroid hormone-related protein exhibits antioxidant features in
osteoblastic cells through its N-terminal and osteostatin domains. Bone Joint Res
2018;7:58-68. DOI: 10.1302/2046-3758.71.BJR-2016-0242.R2.
PMID- 29330345
TI - A computational simulation study to determine the biomechanical influence of
posterior condylar offset and tibial slope in cruciate retaining total knee
arthroplasty.
AB - OBJECTIVES: Posterior condylar offset (PCO) and posterior tibial slope (PTS) are
critical factors in total knee arthroplasty (TKA). A computational simulation was
performed to evaluate the biomechanical effect of PCO and PTS on cruciate
retaining TKA. METHODS: We generated a subject-specific computational model
followed by the development of +/- 1 mm, +/- 2 mm and +/- 3 mm PCO models in the
posterior direction, and -3 degrees , 0 degrees , 3 degrees and 6 degrees PTS
models with each of the PCO models. Using a validated finite element (FE) model,
we investigated the influence of the changes in PCO and PTS on the contact stress
in the patellar button and the forces on the posterior cruciate ligament (PCL),
patellar tendon and quadriceps muscles under the deep knee-bend loading
conditions. RESULTS: Contact stress on the patellar button increased and
decreased as PCO translated to the anterior and posterior directions,
respectively. In addition, contact stress on the patellar button decreased as PTS
increased. These trends were consistent in the FE models with altered PCO. Higher
quadriceps muscle and patellar tendon force are required as PCO translated in the
anterior direction with an equivalent flexion angle. However, as PTS increased,
quadriceps muscle and patellar tendon force reduced in each PCO condition. The
forces exerted on the PCL increased as PCO translated to the posterior direction
and decreased as PTS increased. CONCLUSION: The change in PCO alternatively
provided positive and negative biomechanical effects, but it led to a reduction
in a negative biomechanical effect as PTS increased.Cite this article: K-T. Kang,
Y-G. Koh, J. Son, O-R. Kwon, J-S. Lee, S. K. Kwon. A computational simulation
study to determine the biomechanical influence of posterior condylar offset and
tibial slope in cruciate retaining total knee arthroplasty. Bone Joint Res
2018;7:69-78. DOI: 10.1302/2046-3758.71.BJR-2017-0143.R1.
PMID- 29330346
TI - Underestimation of Staphylococcus aureus (MRSA and MSSA) carriage associated with
standard culturing techniques: One third of carriers missed.
AB - OBJECTIVES: Nasal carriers of Staphylococcus (S.) aureus (MRSA and MSSA) have an
increased risk for healthcare-associated infections. There are currently limited
national screening policies for the detection of S. aureus despite the World
Health Organization's recommendations. This study aimed to evaluate the
diagnostic performance of molecular and culture techniques in S. aureus
screening, determine the cause of any discrepancy between the diagnostic
techniques, and model the potential effect of different diagnostic techniques on
S. aureus detection in orthopaedic patients. METHODS: Paired nasal swabs for
polymerase chain reaction (PCR) assay and culture of S. aureus were collected
from a study population of 273 orthopaedic outpatients due to undergo joint
arthroplasty surgery. RESULTS: The prevalence of MSSA nasal colonization was
found to be between 22.4% to 35.6%. The current standard direct culturing methods
for detecting S. aureus significantly underestimated the prevalence (p = 0.005),
failing to identify its presence in approximately one-third of patients
undergoing joint arthroplasty surgery. CONCLUSION: Modelling these results to
national surveillance data, it was estimated that approximately 5000 to 8000 S.
aureus surgical site infections could be prevented, and approximately $140
million to $950 million (approximately L110 million to L760 million) saved in
treatment costs annually in the United States and United Kingdom combined, by
using alternative diagnostic methods to direct culture in preoperative S. aureus
screening and eradication programmes.Cite this article: S. T. J. Tsang, M. P.
McHugh, D. Guerendiain, P. J. Gwynne, J. Boyd, A. H. R. W. Simpson, T. S. Walsh,
I. F. Laurenson, K. E. Templeton. Underestimation of Staphylococcus aureus (MRSA
and MSSA) carriage associated with standard culturing techniques: One third of
carriers missed. Bone Joint Res 2018;7:79-84. DOI: 10.1302/2046-3758.71.BJR-2017
0175.R1.
PMID- 29330347
TI - Performance of candidates disclosing dyslexia with other candidates in a UK
medical licensing examination: cross-sectional study.
AB - PURPOSE OF THE STUDY: The aim of this study was to compare performance of
candidates who declared an expert-confirmed diagnosis of dyslexia with all other
candidates in the Applied Knowledge Test (AKT) of the Membership of the Royal
College of General Practitioners licensing examination. STUDY DESIGN: We used
routinely collected data from candidates who took the AKT on one or more
occasions between 2010 and 2015. Multivariate logistic regression was used to
analyse performance of candidates who declared dyslexia with all other
candidates, adjusting for candidate characteristics known to be associated with
examination success including age, sex, ethnicity, country of primary medical
qualification, stage of training, number of attempts and time spent completing
the test. RESULTS: The analysis included data from 14 examinations involving 14
801 candidates of which 2.6% (379/14 801) declared dyslexia. The pass rate for
candidates who declared dyslexia was 83.6% compared with 95.0% for other
candidates. After adjusting for covariates linked to examination success
including age, sex, ethnicity, country of primary medical qualification, stage of
training, number of attempts and time spent completing the test dyslexia was not
significantly associated with pass rates in the AKT. Candidates declaring
dyslexia after initially failing the AKT were more likely to have a primary
medical qualification outside the UK. CONCLUSIONS: Performance was similar in AKT
candidates disclosing dyslexia with other candidates once covariates associated
with examination success were adjusted for. Candidates declaring dyslexia after
initially failing the AKT were more likely to have a primary medical
qualification outside the UK.
PMID- 29330348
TI - Weak Epistasis May Drive Adaptation in Recombining Bacteria.
AB - The impact of epistasis on the evolution of multi-locus traits depends on
recombination. While sexually reproducing eukaryotes recombine so frequently that
epistasis between polymorphisms is not considered to play a large role in short
term adaptation, many bacteria also recombine, some to the degree that their
populations are described as "panmictic" or "freely recombining." However,
whether this recombination is sufficient to limit the ability of selection to act
on epistatic contributions to fitness is unknown. We quantify homologous
recombination in five bacterial pathogens and use these parameter estimates in a
multilocus model of bacterial evolution with additive and epistatic effects. We
find that even for highly recombining species (e.g., Streptococcus pneumoniae or
Helicobacter pylori), selection on weak interactions between distant mutations is
nearly as efficient as for an asexual species, likely because homologous
recombination typically transfers only short segments. However, for strong
epistasis, bacterial recombination accelerates selection, with the dynamics
dependent on the amount of recombination and the number of loci. Epistasis may
thus play an important role in both the short- and long-term adaptive evolution
of bacteria, and, unlike in eukaryotes, is not limited to strong effect sizes,
closely linked loci, or other conditions that limit the impact of recombination.
PMID- 29330349
TI - Pharmacologic inhibition of phospholipase C in the brain attenuates early memory
formation in the honeybee (Apis mellifera L.).
AB - Although the molecular mechanisms involved in learning and memory in insects have
been studied intensively, the intracellular signaling mechanisms involved in
early memory formation are not fully understood. We previously demonstrated that
phospholipase C epsilon (PLCe), whose product is involved in calcium signaling,
is almost selectively expressed in the mushroom bodies, a brain structure
important for learning and memory in the honeybee. Here, we pharmacologically
examined the role of phospholipase C (PLC) in learning and memory in the
honeybee. First, we identified four genes for PLC subtypes in the honeybee genome
database. Quantitative reverse transcription-polymerase chain reaction revealed
that, among these four genes, three, including PLCe, were expressed higher in the
brain than in sensory organs in worker honeybees, suggesting their main roles in
the brain. Edelfosine and neomycin, pan-PLC inhibitors, significantly decreased
PLC activities in homogenates of the brain tissues. These drugs injected into the
head of foragers significantly attenuated memory acquisition in comparison with
the control groups, whereas memory retention was not affected. These findings
suggest that PLC in the brain is involved in early memory formation in the
honeybee. To our knowledge, this is the first report of a role for PLC in
learning and memory in an insect.
PMID- 29330350
TI - Selection against BALB/c strain cells in mouse chimaeras.
AB - It has been shown previously that BALB/c strain embryos tend to contribute poorly
to mouse aggregation chimaeras. In the present study we showed that BALB/c cells
were not preferentially allocated to any extraembryonic lineages of mouse
aggregation chimaeras, but their contribution decreased during the early
postimplantation period and they were significantly depleted by E8.5. The
development of BALB/c strain preimplantation embryos lagged behind embryos from
some other strains and the contribution that BALB/c and other embryos made to
chimaeras correlated with their developmental stage at E2.5. This relationship
suggests that the poor contribution of BALB/c embryos to aggregation chimaeras is
at least partly a consequence of generalised selection related to slow or delayed
preimplantation development. The suitability of BALB/c embryos for maximising the
ES cell contribution to mouse ES cell chimaeras is also discussed.
PMID- 29330351
TI - The VEGFA156b isoform is dysregulated in senescent endothelial cells and may be
associated with prevalent and incident coronary heart disease.
AB - Coronary heart disease (CHD) is a leading cause of morbidity in people over 65
years of age; >40% of all deaths are due to this condition. The association
between increasing age and CHD is well documented; the accumulation of senescent
cells in cardiac and vascular tissues may represent one factor underpinning this
observation. We aimed to identify senescence-related expression changes in
primary human senescent cardiomyocytes and endothelial cells and to relate
transcript expression in peripheral blood leucocytes to prevalent and incident
CHD in the InCHIANTI study of aging. We quantified splicing factor expression and
splicing patterns of candidate transcripts in proliferative and senescent later
passage endothelial cells and cardiomyocytes using qRTPCR. Senescence-associated
isoforms also expressed in peripheral blood leucocytes were then examined for
associations with CHD status in 134 pairs of age, sex and BMI-matched CHD cases
and controls. Splicing factor expression was dysregulated in senescent
cardiomyocytes, as previously reported for endothelial cells, as was the
expression of alternatively expressed cardiac and vascular candidate genes in
both cell types. We found nominal associations between the expression of
VEGFA156b and FNI-EIIIIA isoforms in peripheral blood mRNA and CHD status.
Dysregulated splicing factor expression is a key feature of senescent
cardiomyocytes and endothelial cells. Altered splicing of key cardiac or
endothelial genes may contribute to the risk of CHD in the human population.
PMID- 29330352
TI - Dbf4 recruitment by forkhead transcription factors defines an upstream rate
limiting step in determining origin firing timing.
AB - Initiation of eukaryotic chromosome replication follows a spatiotemporal program.
The current model suggests that replication origins compete for a limited pool of
initiation factors. However, it remains to be answered how these limiting factors
are preferentially recruited to early origins. Here, we report that Dbf4 is
enriched at early origins through its interaction with forkhead transcription
factors Fkh1 and Fkh2. This interaction is mediated by the Dbf4 C terminus and
was successfully reconstituted in vitro. An interaction-defective mutant,
dbf4DeltaC, phenocopies fkh alleles in terms of origin firing. Remarkably, genome
wide replication profiles reveal that the direct fusion of the DNA-binding domain
(DBD) of Fkh1 to Dbf4 restores the Fkh-dependent origin firing but interferes
specifically with the pericentromeric origin activation. Furthermore, Dbf4
interacts directly with Sld3 and promotes the recruitment of downstream limiting
factors. These data suggest that Fkh1 targets Dbf4 to a subset of noncentromeric
origins to promote early replication in a manner that is reminiscent of the
recruitment of Dbf4 to pericentromeric origins by Ctf19.
PMID- 29330353
TI - Afadin and RhoA control pancreatic endocrine mass via lumen morphogenesis.
AB - Proper lumen morphogenesis during pancreas development is critical to endocrine
and exocrine cell fate. Recent studies showed that a central network of lumens
(termed core), but not the surrounding terminal branches (termed periphery),
produces most islet endocrine cells. To date, it remains unclear how pancreatic
lumens form and remodel and which aspects of lumen morphogenesis influence cell
fate. Importantly, models testing the function of the central lumen network as an
endocrine niche are lacking. Here, we identify mechanisms underlying lumen
formation and remodeling and show that central lumen network morphogenesis
impacts pancreatic endocrine mass. We show that loss of the scaffolding protein
Afadin disrupts de novo lumenogenesis and lumen continuity in the tip epithelium.
Codepletion of the actomyosin regulator RhoA and Afadin results in defects in the
central lumens and arrests lumen remodeling. This arrest leads to prolonged
perdurance of the central lumen network over developmental time and expansion of
the endocrine progenitor population and, eventually, endocrine mass. Our study
uncovers essential roles of Afadin and RhoA in pancreatic central lumen
morphogenesis, which subsequently determines endocrine cell mass.
PMID- 29330354
TI - The RES complex is required for efficient transformation of the precatalytic B
spliceosome into an activated Bact complex.
AB - The precise function of the trimeric retention and splicing (RES) complex in pre
mRNA splicing remains unclear. Here we dissected the role of RES during the
assembly and activation of yeast spliceosomes. The efficiency of pre-mRNA
splicing was significantly lower in the absence of the RES protein Snu17, and the
recruitment of its binding partners, Pml1 (pre-mRNA leakage protein 1) and Bud13
(bud site selection protein 13), to the spliceosome was either abolished or
substantially reduced. RES was not required for the assembly of spliceosomal B
complexes, but its absence hindered efficient Bact complex formation. DeltaRES
spliceosomes were no longer strictly dependent on Prp2 activity for their
catalytic activation, suggesting that they are structurally compromised. Addition
of Prp2, Spp2, and UTP to affinity-purified DeltaRES B or a mixture of B/Bact
complexes formed on wild-type pre-mRNA led to their disassembly. However, no
substantial disassembly was observed with DeltaRES spliceosomes formed on a
truncated pre-mRNA that allows Prp2 binding but blocks its activity. Thus, in the
absence of RES, Prp2 appears to bind prematurely, leading to the disassembly of
the DeltaRES B complexes to which it binds. Our data suggest that Prp2 can
dismantle B complexes with an aberrant protein composition, suggesting that it
may proofread the spliceosome's RNP structure prior to activation.
PMID- 29330356
TI - Metabolic and molecular changes associated with the increased skeletal muscle
insulin action 24-48 h after exercise in young and old humans.
AB - The molecular and metabolic mechanisms underlying the increase in insulin
sensitivity (i.e. increased insulin-stimulated skeletal muscle glucose uptake,
phosphorylation and storage as glycogen) observed from 12 to 48 h following a
single bout of exercise in humans remain unresolved. Moreover, whether these
mechanisms differ with age is unclear. It is well established that a single bout
of exercise increases the translocation of the glucose transporter, GLUT4, to the
plasma membrane. Previous research using unilateral limb muscle contraction
models in combination with hyperinsulinaemia has demonstrated that the increase
in insulin sensitivity and glycogen synthesis 24 h after exercise is also
associated with an increase in hexokinase II (HKII) mRNA and protein content,
suggesting an increase in the capacity of the muscle to phosphorylate glucose and
divert it towards glycogen synthesis. Interestingly, this response is altered in
older individuals for up to 48 h post exercise and is associated with molecular
changes in skeletal muscle tissue that are indicative of reduced lipid oxidation,
increased lipogenesis, increased inflammation and a relative inflexibility of
changes in intramyocellular lipid (IMCL) content. Reduced insulin sensitivity
(insulin resistance) is generally related to IMCL content, particularly in the
subsarcolemmal (SSL) region, and both are associated with increasing age. Recent
research has demonstrated that ageing per se appears to cause an exacerbated
lipolytic response to exercise that may result in SSL IMCL accumulation. Further
research is required to determine if increased IMCL content affects HKII
expression in the days after exercise in older individuals, and the effect of
this on skeletal muscle insulin action.
PMID- 29330355
TI - Fatty acids and related lipid mediators in the regulation of cutaneous
inflammation.
AB - Human skin has a distinct profile of fatty acids and related bioactive lipid
mediators that regulate many aspects of epidermal and dermal homeostasis,
including immune and inflammatory reactions. Sebum lipids act as effective
antimicrobial agents, shape immune cell communications and contribute to the
epidermal lipidome. The essential fatty acid linoleic acid is crucial for the
structure of the epidermal barrier, while polyunsaturated fatty acids act as
precursors to eicosanoids, octadecanoids and docosanoids through cyclooxygenase,
lipoxygenase and cytochrome P450 monooxygenase-mediated reactions, and
endocannabinoids and N-acyl ethanolamines. Cross-communication between these
families of bioactive lipids suggests that their cutaneous activities should be
considered as part of a wider metabolic network that can be targeted to maintain
skin health, control inflammation and improve skin pathologies.
PMID- 29330357
TI - Knockdown of Phospholipase Cepsilon (PLCepsilon) Inhibits Cell Proliferation via
Phosphatase and Tensin Homolog Deleted on Chromosome 10 (PTEN)/AKT Signaling
Pathway in Human Prostate Cancer.
AB - BACKGROUND Phospholipase Cepsilon (PLCepsilon), a member of the plc family, has
been extensively studied to reveal its role in the regulation of different cell
functions, but understanding of the underlying mechanisms remains limited. In the
present study, we explored the effects of PLCepsilon on PTEN (phosphatase and
tensin homolog deleted on chromosome 10) in cell proliferation in prostate cancer
cells. MATERIAL AND METHODS We assessed PLCepsilon and PTEN expression in human
benign prostate tissues compared to prostate cancer tissues by
immunohistochemistry. Lentivirus-shPLCepsilon (LV-shPLCepsilon) was designed to
silence PLCepsilon expression in DU145 and PC3 cell lines, and the effectiveness
was tested by qRT-PCR and Western blotting. MTT assay and colony formation assay
were conducted to observe cell proliferation. Western blotting and
immunofluorescence assays were used to detect changed PTEN expression in DU145.
RESULTS We observed that PLCepsilon expression was reduced in human benign
prostate tissues compared to prostate cancer tissues, while PTEN expression
showed the opposite trend. Silencing of the PLCepsilon gene significantly
inhibited cell proliferation in DU145 and PC3 cell lines. DU145 is a PTEN
expressing cell, while PC3 is PTEN-deficient. After infection by LV-shPLCepsilon,
we noticed that PTEN expression was up-regulated in DU145 cells but not in PC3
cells. Furthermore, we found that PLCepsilon gene knockdown decreased P-AKT
protein levels, but AKT protein levels were not affected. Immunofluorescence
assays showed that PTEN expression had an intracellular distribution change in
the DU145 cell line, and Western blot analysis showed that PTEN was obviously up
regulated in cell nucleus and cytoplasm. CONCLUSIONS PLCepsilon is an oncogene,
and knockdown of expression of PLCe inhibits PCa cells proliferation via the
PTEN/AKT signaling pathway.
PMID- 29330358
TI - Pathogenesis of bone disease in multiple myeloma: from bench to bedside.
AB - Osteolytic bone disease is the hallmark of multiple myeloma, which deteriorates
the quality of life of myeloma patients, and it affects dramatically their
morbidity and mortality. The basis of the pathogenesis of myeloma-related bone
disease is the uncoupling of the bone-remodeling process. The interaction between
myeloma cells and the bone microenvironment ultimately leads to the activation of
osteoclasts and suppression of osteoblasts, resulting in bone loss. Several
intracellular and intercellular signaling cascades, including RANK/RANKL/OPG,
Notch, Wnt, and numerous chemokines and interleukins are implicated in this
complex process. During the last years, osteocytes have emerged as key regulators
of bone loss in myeloma through direct interactions with the myeloma cells. The
myeloma-induced crosstalk among the molecular pathways establishes a positive
feedback that sustains myeloma cell survival and continuous bone destruction,
even when a plateau phase of the disease has been achieved. Targeted therapies,
based on the better knowledge of the biology, constitute a promising approach in
the management of myeloma-related bone disease and several novel agents are
currently under investigation. Herein, we provide an insight into the underlying
pathogenesis of bone disease and discuss possible directions for future studies.
PMID- 29330359
TI - Strong grain neighbour effects in polycrystals.
AB - Anisotropy in single-crystal properties of polycrystals controls both the overall
response of the aggregates and patterning of local stress/strain distributions,
the extremes of which govern failure processes. Improving the understanding of
grain-grain interactions has important consequences for in-service performance
limits. Three-dimensional synchrotron X-ray diffraction was used to study the
evolution of grain-resolved stresses over many contiguous grains in Zr and Ti
polycrystals deformed in situ. In a significant fraction of grains, the stress
along the loading axis was found to decrease during tensile plastic flow just
beyond the macroscopic yield point; this is in the absence of deformation
twinning and is a surprising behaviour. It is shown that this phenomenon is
controlled by the crystallographic orientation of the grain and its immediate
neighbours, particularly those adjacent along the loading axis.
PMID- 29330360
TI - Fibre-optic metadevice for all-optical signal modulation based on coherent
absorption.
AB - Recently, coherent control of the optical response of thin films in standing
waves has attracted considerable attention, ranging from applications in
excitation-selective spectroscopy and nonlinear optics to all-optical image
processing. Here, we show that integration of metamaterial and optical fibre
technologies allows the use of coherently controlled absorption in a fully
fiberized and packaged switching metadevice. With this metadevice, which controls
light with light in a nanoscale plasmonic metamaterial film on an optical fibre
tip, we provide proof-of-principle demonstrations of logical functions XOR, NOT
and AND that are performed within a coherent fibre network at wavelengths between
1530 and 1565 nm. The metadevice has been tested at up to 40 gigabits per second
and sub-milliwatt power levels. Since coherent absorption can operate at the
single-photon level and with 100 THz bandwidth, we argue that the demonstrated
all-optical switch concept has potential applications in coherent and quantum
information networks.
PMID- 29330361
TI - Discovery of microRNA-target modules of African rice (Oryza glaberrima) under
salinity stress.
AB - Oryza glaberrima is the second edible rice in the genus Oryza. It is grown in the
African countries. miRNAs are regulatory molecules that are involved in every
domains of gene expression including salinity stress response. Although several
miRNAs have been reported from various species of Oryza, yet none of them are
from this species. Salt treated (200 mM NaCl for 48 h) and control smallRNA
libraries of RAM-100, a salt tolerant genotype, each with 2 replications
generated 150 conserve and 348 novel miRNAs. We also used smallRNAseq data of
NCBI of O. glaberrima to discover additional 246 known miRNAs. Totally, 29 known
and 32 novel miRNAs were differentially regulated under salinity stress. Gene
ontology and KEGG analysis indicated several targets were involved in vital
biological pathways of salinity stress tolerance. Expression of selected miRNAs
as indicated by Illumina data were found to be coherent with real time-PCR
analysis. However, target gene expression was inversely correlated with their
corresponding miRNAs. Finally based upon present results as well as existing
knowledge of literature, we proposed the miRNA-target modules that were induced
by salinity stress. Therefore, the present findings provide valuable information
about miRNA-target networks in salinity adaption of O. glaberrima.
PMID- 29330362
TI - Dynamic modelling of the mTOR signalling network reveals complex emergent
behaviours conferred by DEPTOR.
AB - The mechanistic Target of Rapamycin (mTOR) signalling network is an
evolutionarily conserved network that controls key cellular processes, including
cell growth and metabolism. Consisting of the major kinase complexes mTOR Complex
1 and 2 (mTORC1/2), the mTOR network harbours complex interactions and feedback
loops. The DEP domain-containing mTOR-interacting protein (DEPTOR) was recently
identified as an endogenous inhibitor of both mTORC1 and 2 through direct
interactions, and is in turn degraded by mTORC1/2, adding an extra layer of
complexity to the mTOR network. Yet, the dynamic properties of the DEPTOR-mTOR
network and the roles of DEPTOR in coordinating mTORC1/2 activation dynamics have
not been characterised. Using computational modelling, systems analysis and
dynamic simulations we show that DEPTOR confers remarkably rich and complex
dynamic behaviours to mTOR signalling, including abrupt, bistable switches,
oscillations and co-existing bistable/oscillatory responses. Transitions between
these distinct modes of behaviour are enabled by modulating DEPTOR expression
alone. We characterise the governing conditions for the observed dynamics by
elucidating the network in its vast multi-dimensional parameter space, and
develop strategies to identify core network design motifs underlying these
dynamics. Our findings provide new systems-level insights into the complexity of
mTOR signalling contributed by DEPTOR.
PMID- 29330363
TI - Disulfide isomerization reactions in titin immunoglobulin domains enable a mode
of protein elasticity.
AB - The response of titin to mechanical forces is a major determinant of the function
of the heart. When placed under a pulling force, the unstructured regions of
titin uncoil while its immunoglobulin (Ig) domains unfold and extend. Using
single-molecule atomic force microscopy, we show that disulfide isomerization
reactions within Ig domains enable a third mechanism of titin elasticity.
Oxidation of Ig domains leads to non-canonical disulfide bonds that stiffen titin
while enabling force-triggered isomerization reactions to more extended states of
the domains. Using sequence and structural analyses, we show that 21% of titin's
I-band Ig domains contain a conserved cysteine triad that can engage in disulfide
isomerization reactions. We propose that imbalance of the redox status of
myocytes can have immediate consequences for the mechanical properties of the
sarcomere via alterations of the oxidation state of titin domains.
PMID- 29330364
TI - Polypharmacy through Phage Display: Selection of Glucagon and GLP-1 Receptor Co
agonists from a Phage-Displayed Peptide Library.
AB - A promising emerging area for the treatment of obesity and diabetes is
combinatorial hormone therapy, where single-molecule peptides are rationally
designed to integrate the complementary actions of multiple endogenous
metabolically-related hormones. We describe here a proof-of-concept study on
developing unimolecular polypharmacy agents through the use of selection methods
based on phage-displayed peptide libraries (PDL). Co-agonists of the glucagon
(GCG) and GLP-1 receptors were identified from a PDL sequentially selected on
GCGR- and GLP1R-overexpressing cells. After two or three rounds of selection,
7.5% of randomly picked clones were GLP1R/GCGR co-agonists, and a further 1.53%
were agonists of a single receptor. The phages were sequenced and 35
corresponding peptides were synthesized. 18 peptides were potent co-agonists, 8
of whom showed EC50 <= 30 pM on each receptor, comparable to the best rationally
designed co-agonists reported in the literature. Based on literature examples,
two sequences were engineered to stabilize against dipeptidyl peptidase IV
cleavage and prolong the in vivo half-life: the engineered peptides were
comparably potent to the parent peptides on both receptors, highlighting the
potential use of phage-derived peptides as therapeutic agents. The strategy
described here appears of general value for the discovery of optimized
polypharmacology paradigms across several metabolically-related hormones.
PMID- 29330365
TI - Engineered nanointerfaces for microfluidic isolation and molecular profiling of
tumor-specific extracellular vesicles.
AB - Extracellular vesicles (EVs) carry RNA, DNA, proteins, and lipids. Specifically,
tumor-derived EVs have the potential to be utilized as disease-specific
biomarkers. However, a lack of methods to isolate tumor-specific EVs has limited
their use in clinical settings. Here we report a sensitive analytical
microfluidic platform (EVHB-Chip) that enables tumor-specific EV-RNA isolation
within 3 h. Using the EVHB-Chip, we achieve 94% tumor-EV specificity, a limit of
detection of 100 EVs per MUL, and a 10-fold increase in tumor RNA enrichment in
comparison to other methods. Our approach allows for the subsequent release of
captured tumor EVs, enabling downstream characterization and functional studies.
Processing serum and plasma samples from glioblastoma multiforme (GBM) patients,
we can detect the mutant EGFRvIII mRNA. Moreover, using next-generation RNA
sequencing, we identify genes specific to GBM as well as transcripts that are
hallmarks for the four genetic subtypes of the disease.
PMID- 29330366
TI - Each protomer of a dimeric YidC functions as a single membrane insertase.
AB - The membrane insertase YidC catalyzes the entrance of newly synthesized proteins
into the lipid bilayer. As an integral membrane protein itself, YidC can be found
as a monomer, a dimer or also as a member of the holotranslocase SecYEGDF-YajC
YidC. To investigate whether the dimeric YidC is functional and whether two
copies cooperate to insert a single substrate, we constructed a fusion protein
where two copies of YidC are connected by a short linker peptide. The 120 kDa
protein is stable and functional as it supports the membrane insertion of the M13
procoat protein, the C-tailed protein SciP and the fusion protein Pf3-Lep.
Mutations that inhibit either protomer do not inactivate the insertase and rather
keep it functional. When both protomers are defective, the substrate proteins
accumulate in the cytoplasm. This suggests that the dimeric YidC operates as two
insertases. Consistent with this, we show that the dimeric YidC can bind two
substrate proteins simultaneously, suggesting that YidC indeed functions as a
monomer.
PMID- 29330367
TI - Characterization of human small heat shock protein HSPB1 alpha-crystallin domain
localized mutants associated with hereditary motor neuron diseases.
AB - Congenital mutations in human small heat shock protein HSPB1 (HSP27) have been
linked to Charcot-Marie-Tooth disease, a commonly occurring peripheral
neuropathy. Understanding the molecular mechanism of such mutations is
indispensable towards developing future therapies for this currently incurable
disorder. Here we describe the physico-chemical properties of the autosomal
dominant HSPB1 mutants R127W, S135F and R136W. Despite having a nominal effect on
thermal stability, the three mutations induce dramatic changes to quaternary
structure. At high concentrations or under crowding conditions, the mutants form
assemblies that are approximately two times larger than those formed by the wild
type protein. At low concentrations, the mutants have a higher propensity to
dissociate into small oligomers, while the dissociation of R127W and R135F
mutants is enhanced by MAPKAP kinase-2 mediated phosphorylation. Specific
differences are observed in the ability to form hetero-oligomers with the
homologue HSPB6 (HSP20). For wild-type HSPB1 this only occurs at or above
physiological temperature, whereas the R127W and S135F mutants form hetero
oligomers with HSPB6 at 4 degrees C, and the R136W mutant fails to form hetero
oligomers. Combined, the results suggest that the disease-related mutations of
HSPB1 modify its self-assembly and interaction with partner proteins thus
affecting normal functioning of HSPB1 in the cell.
PMID- 29330368
TI - Evidence of subtle genetic structure in the sympatric species Mullus barbatus and
Mullus surmuletus (Linnaeus, 1758) in the Mediterranean Sea.
AB - Using thirteen microsatellite loci for Mullus barbatus and Mullus surmuletus
collected in the Mediterranean Sea, the biogeographic boundaries, genetic
distribution among and within basins and the impact of prolonged exploitation in
both species were investigated as a basis for understanding their population
dynamics and for improving Mullus spp. stock management. Different level of
diversity indices among these co-occurring species were obtained, with M.
barbatus showing higher allele richness and higher mean observed and expected
heterozygosity than M. surmuletus. Reduced contemporary effective population size
(Ne) and M-ratio values found in both species likely reflects recent demographic
changes, due to a combination of high fishing pressures, habitat fragmentation
and naturally occurring fluctuations in population size. Different patterns of
genetic connectivity among populations sampled within the Mediterranean were
observed for both species. Higher genetic structure was found for M. barbatus as
opposed to a more homogenous pattern observed in M. surmuletus samples. Adriatic
populations, previously considered panmictic and isolated from other
Mediterranean regions, showed geographical partitioning within the basin but also
population connectivity with the northern Ionian and Tyrrhenian Seas. Our results
highlight the need for temporal sampling in understanding the complex pattern of
population connectivity in the Mediterranean, particularly for management
purposes.
PMID- 29330369
TI - Bio-templated fabrication of three-dimensional network activated carbons derived
from mycelium pellets for supercapacitor applications.
AB - In this work, a three-dimensional porous mycelium-derived activated carbon (3D
MAC) was fabricated via a facile bio-templating method using mycelium pellets as
both the carbon source and the bio-template. After ZnCl2 activation and high
temperature carbonization, the specific thread-like chain structure of mycelium
in the pellets can be maintained effectively. The hyphae and junctions of the
cross-linking hyphae form nanowires and carbon nanoparticles that link with the
neighboring nanoparticles to form a network structure. By adding NH4Cl, foreign
nitrogen element doped (N-doped) 3D-MAC was obtained, which has a hierarchical
porous structure composed of micropores and macropores. And the multiple pore
size distribution benefits from ZnCl2 activation, the specific 3D structure and
gas blowing. Meanwhile, the introduction of some hydrophilic groups and abundant
N-containing functional groups in extrinsic N-doped 3D-MAC contributes to
improving the Faradaic pseudocapacitance, respectively. A specific capacitance of
237.2 F g-1 at 10 mV s-1 was displayed, which is more than 1.5 times that of 3D
MAC. Even at the large scan rate of 500 mV s-1, N-doped 3D-MAC still reveals a
nearly symmetric rectangular shape, demonstrating great potential as a high
performance supercapacitor electrode material due to the synergistic effects of
its 3D hierarchical porous structure and various functional groups.
PMID- 29330370
TI - A RNA-Sequencing approach for the identification of novel long non-coding RNA
biomarkers in colorectal cancer.
AB - Long non-coding RNAs (lncRNAs) have been implicated in human pathology, however,
their role in colorectal carcinogenesis have not been fully elucidated. In the
current study, whole-transcriptome analysis was performed in 3 pairs of
colorectal cancer (CRC) and matched normal mucosa (NM) by RNA sequencing (RNA
seq). Followed by confirmation using the Cancer Genome Atlas (TCGA) dataset, we
identified 27 up-regulated and 22 down-regulated lncRNAs in CRC. Up-regulation of
four lncRNAs, hereby named colorectal cancer associated lncRNA (CRCAL)-1
[AC021218.2], CRCAL-2 [LINC00858], CRCAL-3 [RP11-138J23.1] and CRCAL-4 [RP11
435O5.2], was further validated by real-time RT-PCR in 139 colorectal neoplasms
and matched NM tissues. Knockdown of CRCAL-3 and CRCAL-4 in colon cancer cells
reduced cell viability and colony formation ability, and induced cell cycle
arrest. TCGA dataset supported the associations of CRCAL-3 and CRCAL-4 with cell
cycle and revealed a co-expression network comprising dysregulated lncRNAs
associated with protein-coding genes. In conclusion, RNA-seq identified numbers
of novel lncRNAs dysregulated in CRC. In vitro experiments and GO term enrichment
analysis indicated the functional relevance of CRCAL-3 and CRCAL-4 in association
with cell cycle. Our data highlight the capability of RNA-seq to discover novel
lncRNAs involved in human carcinogenesis, which may serve as alternative
biomarkers and/or molecular treatment targets.
PMID- 29330371
TI - Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA
synthesis fidelity between retroviral reverse transcriptases.
AB - In M13mp2 lacZalpha forward mutation assays measuring intrinsic fidelity of DNA
dependent DNA synthesis, wild-type human immunodeficiency virus type 1 (HIV-1)
RTs of group M/subtype B previously showed >10-fold higher error rates than
murine leukaemia virus (MLV) and avian myeloblastosis virus (AMV) RTs. An adapted
version of the assay was used to obtain error rates of RNA-dependent DNA
synthesis for several RTs, including wild-type HIV-1BH10, HIV-1ESP49, AMV and MLV
RTs, and the high-fidelity mutants of HIV-1ESP49 RT K65R and K65R/V75I. Our
results showed that there were less than two-fold differences in fidelity between
the studied RTs with error rates ranging within 2.5 * 10-5 and 3.5 * 10-5. These
results were consistent with the existence of a transcriptional inaccuracy
threshold, generated by the RNA polymerase while synthesizing the RNA template
used in the assay. A modest but consistent reduction of the inaccuracy threshold
was achieved by lowering the pH and Mg2+ concentration of the transcription
reaction. Despite assay limitations, we conclude that HIV-1BH10 and HIV-1ESP49
RTs are less accurate when copying DNA templates than RNA templates. Analysis of
the RNA-dependent mutational spectra revealed a higher tendency to introduce
large deletions at the initiation of reverse transcription by all HIV-1 RTs
except the double-mutant K65R/V75I.
PMID- 29330373
TI - The Association of Fit-Fat Index with Incident Diabetes in Japanese Men: A
Prospective Cohort Study.
AB - Type 2 diabetes is increasing globally and in Asia. The purpose of this study was
to examine the association of a fit-fat index (FFI) with diabetes incidence among
Japanese men. In total 5,014 men aged 18-64 years old, who had an annual health
check up with no history of major chronic disease at baseline from 2002 to 2009
were observed. CRF was estimated via cycle ergometry. Overall, 7.6% of the men
developed diabetes. The mean follow-up period was 5.3 years. Hazard ratios, 95%
confidence intervals and P trend for diabetes incidence were obtained using the
Cox proportional hazards model while adjusting for confounding variables. High
FFI demonstrated lower risk 0.54 (0.36-0.82) compared to low BMI 0.63 (0.44
0.90), low WHtR 0.64 (0.41-1.02), and High CRF 0.72 (0.51-1.03). FFI showed a
marginally stronger dose response relationship across quartiles (P (trend)
=0.001) compared to BMI (P (trend) =0.002), WHtR (P (trend) =0.055), and CRF (P
(trend) =0.005). Overall, both fitness and fatness play independent roles in
determining diabetes incidence in Japanese men. FFI may be a more advantageous
physical fitness measure because it can account for changes in fitness and/or
fatness.
PMID- 29330374
TI - Predicting Fibrosis Progression in Renal Transplant Recipients Using Laser-Based
Infrared Spectroscopic Imaging.
AB - Renal transplants have not seen a significant improvement in their 10-year graft
life. Chronic damage accumulation often leads to interstitial fibrosis and
tubular atrophy (IF/TA) and thus graft function loss over time. For this reason,
IF/TA has been the chief suspect for a potential prognostic marker for long term
outcomes. In this study, we have used infrared spectroscopic (IR) imaging to
interrogate the biochemistry of regions of fibrosis from renal transplant
biopsies to identify a biochemical signature that can predict rapid progression
of fibrosis. IR imaging represents an approach that permits label-free
biochemical imaging of human tissues towards identifying novel biomarkers for
disease diagnosis or prognosis. Two cohorts were identified as progressors (n =
5, > 50% fibrosis increase between time points) and non-progressors (n = 5, < 5%
increase between time points). Each patient had an early time point and late time
point biopsy. Collagen associated carbohydrate moieties (nu(C-O), 1035 cm-1 and
nu(C-O-C),1079 cm-1) spectral ratios demonstrated good separation between the two
cohorts (p = 0.001). This was true for late and early time point biopsies
suggesting the regions of fibrosis are biochemically altered in cases undergoing
progressive fibrosis. Thus, IR imaging can potentially predict rapid progression
of fibrosis using histologically normal early time point biopsies.
PMID- 29330372
TI - Non-estrogenic Xanthohumol Derivatives Mitigate Insulin Resistance and Cognitive
Impairment in High-Fat Diet-induced Obese Mice.
AB - Xanthohumol (XN), a prenylated flavonoid from hops, improves dysfunctional
glucose and lipid metabolism in animal models of metabolic syndrome (MetS).
However, its metabolic transformation into the estrogenic metabolite, 8
prenylnaringenin (8-PN), poses a potential health concern for its use in humans.
To address this concern, we evaluated two hydrogenated derivatives, alpha,beta
dihydro-XN (DXN) and tetrahydro-XN (TXN), which showed negligible affinity for
estrogen receptors alpha and beta, and which cannot be metabolically converted
into 8-PN. We compared their effects to those of XN by feeding C57BL/6J mice a
high-fat diet (HFD) containing XN, DXN, or TXN for 13 weeks. DXN and TXN were
present at higher concentrations than XN in plasma, liver and muscle. Mice
administered XN, DXN or TXN showed improvements of impaired glucose tolerance
compared to the controls. DXN and TXN treatment resulted in a decrease of HOMA-IR
and plasma leptin. C2C12 embryonic muscle cells treated with DXN or TXN exhibited
higher rates of uncoupled mitochondrial respiration compared to XN and the
control. Finally, XN, DXN, or TXN treatment ameliorated HFD-induced deficits in
spatial learning and memory. Taken together, DXN and TXN could ameliorate the
neurocognitive-metabolic impairments associated with HFD-induced obesity without
risk of liver injury and adverse estrogenic effects.
PMID- 29330375
TI - Intra-Specific Latitudinal Clines in Leaf Carbon, Nitrogen, and Phosphorus and
their Underlying Abiotic Correlates in Ruellia Nudiflora.
AB - While plant intra-specific variation in the stoichiometry of nutrients and carbon
is well documented, clines for such traits have been less studied, despite their
potential to reveal the mechanisms underlying such variation. Here we analyze
latitudinal variation in the concentration of leaf nitrogen (N), phosphorus (P),
carbon (C) and their ratios across 30 populations of the perennial herb Ruellia
nudiflora. In addition, we further determined whether climatic and soil variables
underlie any such latitudinal clines in leaf traits. The sampled transect spanned
5 degrees latitude (ca. 900 km) and exhibited a four-fold precipitation gradient
and 2 degrees C variation in mean annual temperature. We found that leaf P
concentration increased with precipitation towards lower latitudes, whereas N and
C did not exhibit latitudinal clines. In addition, N:P and C:P decreased towards
lower latitudes and latitudinal variation in the former was weakly associated
with soil conditions (clay content and cation exchange capacity); C:N did not
exhibit a latitudinal gradient. Overall, these results emphasize the importance
of addressing and disentangling the simultaneous effects of abiotic factors
associated with intra-specific clines in plant stoichiometric traits, and
highlight the previously underappreciated influence of abiotic factors on plant
nutrients operating under sharp abiotic gradients over smaller spatial scales.
PMID- 29330376
TI - Layer number identification of CVD-grown multilayer graphene using Si peak
analysis.
AB - Since the successful exfoliation of graphene, various methodologies have been
developed to identify the number of layers of exfoliated graphene. The optical
contrast, Raman G-peak intensity, and 2D-peak line-shape are currently widely
used as the first level of inspection for graphene samples. Although the
combination analysis of G- and 2D-peaks is powerful for exfoliated graphene
samples, its use is limited in chemical vapor deposition (CVD)-grown graphene
because CVD-grown graphene consists of various domains with randomly rotated
crystallographic axes between layers, which makes the G- and 2D-peaks analysis
difficult for use in number identification. We report herein that the Raman Si
peak intensity can be a universal measure for the number identification of
multilayered graphene. We synthesized a few-layered graphene via the CVD method
and performed Raman spectroscopy. Moreover, we measured the Si-peak intensities
from various individual graphene domains and correlated them with the
corresponding layer numbers. We then compared the normalized Si-peak intensity of
the CVD-grown multilayer graphene with the exfoliated multilayer graphene as a
reference and successfully identified the layer number of the CVD-grown graphene.
We believe that this Si-peak analysis can be further applied to various 2
dimensional (2D) materials prepared by both exfoliation and chemical growth.
PMID- 29330378
TI - Mechanisms controlling the impact of multi-year drought on mountain hydrology.
AB - Mountain runoff ultimately reflects the difference between precipitation (P) and
evapotranspiration (ET), as modulated by biogeophysical mechanisms that intensify
or alleviate drought impacts. These modulating mechanisms are seldom measured and
not fully understood. The impact of the warm 2012-15 California drought on the
heavily instrumented Kings River basin provides an extraordinary opportunity to
enumerate four mechanisms that controlled the impact of drought on mountain
hydrology. Two mechanisms intensified the impact: (i) evaporative processes have
first access to local precipitation, which decreased the fractional allocation of
P to runoff in 2012-15 and reduced P-ET by 30% relative to previous years, and
(ii) 2012-15 was 1 degrees C warmer than the previous decade, which increased ET
relative to previous years and reduced P-ET by 5%. The other two mechanisms
alleviated the impact: (iii) spatial heterogeneity and the continuing supply of
runoff from higher elevations increased 2012-15 P-ET by 10% relative to that
expected for a homogenous basin, and iv) drought-associated dieback and wildfire
thinned the forest and decreased ET, which increased 2016 P-ET by 15%. These
mechanisms are all important and may offset each other; analyses that neglect one
or more will over or underestimate the impact of drought and warming on mountain
runoff.
PMID- 29330377
TI - Phenotypic and Functional Characterization of Peripheral Sensory Neurons derived
from Human Embryonic Stem Cells.
AB - The dorsal root ganglia (DRG) consist of a multitude of sensory neuronal subtypes
that function to relay sensory stimuli, including temperature, pressure, pain and
position to the central nervous system. Our knowledge of DRG sensory neurons have
been predominantly driven by animal studies and considerably less is known about
the human DRG. Human embryonic stem cells (hESC) are valuable resource to help
close this gap. Our previous studies reported an efficient system for deriving
neural crest and DRG sensory neurons from hESC. Here we show that this
differentiation system gives rise to heterogeneous populations of sensory
neuronal subtypes as demonstrated by phenotypic and functional analyses.
Furthermore, using microelectrode arrays the maturation rate of the hESC-derived
sensory neuronal cultures was monitored over 8 weeks in culture, showing their
spontaneous firing activities starting at about 12 days post-differentiation and
reaching maximum firing at about 6 weeks. These studies are highly valuable for
developing an in vitro platform to study the diversity of sensory neuronal
subtypes found within the human DRG.
PMID- 29330380
TI - Automatic segmentation of the solid core and enclosed vessels in subsolid
pulmonary nodules.
AB - Subsolid pulmonary nodules are commonly encountered in lung cancer screening and
clinical routine. Compared to other nodule types, subsolid nodules are associated
with a higher malignancy probability for which the size and mass of the nodule
and solid core are important indicators. However, reliably measuring these
characteristics on computed tomography (CT) can be hampered by the presence of
vessels encompassed by the nodule, since vessels have similar CT attenuation as
solid cores. This can affect treatment decisions and patient management. We
present a method based on voxel classification to automatically identify vessels
and solid cores in given subsolid nodules on CT. Three experts validated our
method on 170 screen-detected subsolid nodules from the Multicentric Italian Lung
Disease trial. The agreement between the proposed method and the observers was
substantial for vessel detection and moderate for solid core detection, which was
similar to the inter-observer agreement. We found a relatively high variability
in the inter-observer agreement and low method-observer agreements for
delineating the borders of vessels and solid cores, illustrating the difficulty
of this task. However, 92.4% of the proposed vessel and 80.6% of the proposed
solid core segmentations were labeled as usable in clinical practice by the
majority of experts.
PMID- 29330379
TI - Identification of shared genetic variants between schizophrenia and lung cancer.
AB - Epidemiology studies suggest associations between schizophrenia and cancer.
However, the underlying genetic mechanisms are not well understood, and difficult
to identify from epidemiological data. We investigated if there is a shared
genetic architecture between schizophrenia and cancer, with the aim to identify
specific overlapping genetic loci. First, we performed genome-wide enrichment
analysis and second, we analyzed specific loci jointly associated with
schizophrenia and cancer by the conjunction false discovery rate. We analyzed the
largest genome-wide association studies of schizophrenia and lung, breast,
prostate, ovary, and colon-rectum cancer including more than 220,000 subjects,
and included genetic association with smoking behavior. Polygenic enrichment of
associations with lung cancer was observed in schizophrenia, and weak enrichment
for the remaining cancer sites. After excluding the major histocompatibility
complex region, we identified three independent loci jointly associated with
schizophrenia and lung cancer. The strongest association included nicotinic
acetylcholine receptors and is an established pleiotropic locus shared between
lung cancer and smoking. The two other loci were independent of genetic
association with smoking. Functional analysis identified downstream pleiotropic
effects on epigenetics and gene-expression in lung and brain tissue. These
findings suggest that genetic factors may explain partly the observed
epidemiological association of lung cancer and schizophrenia.
PMID- 29330381
TI - Paper-based inkjet bioprinting to detect fluorescence resonance energy transfer
for the assessment of anti-inflammatory activity.
AB - For the first time, a paper-based fluorescence resonance energy transfer (FRET)
determination with cyclic AMP (cAMP)-specific phosphodiesterase 4B (PDE4B)
inhibitory assay using an inkjet-printing technique is proposed. Non-fabricated
parchment paper is found to constitute a unique substrate to measure fluorescent
energy transfer, due to its insignificant self-absorption, and enables efficient
sample interaction. Here, we report the responsive FRET signals generated on
paper, upon sequentially printing reaction components on parchment paper using a
conventional inkjet printer equipped with four cartridges. After printing, the
energy emitted by Eu chelate was transferred by FRET to ULight molecule on paper,
detected at 665 nm. In the absence of free cAMP, a maximum FRET signal was
achieved on paper, while a decrease in FRET signals was recorded when free cAMP
produced by PDE4B inhibitors compete with Eu-cAMP, binding with ULight-mAb. The
IM50 value was determined as 2.46 * 10-13 mole for roliparm and 1.86 * 10-13 mole
for roflumilast, to effectively inhibit PDE4B activity. Inkjet printing-based
FRET signal determination utilizes components that are less than the femtomole
range, which was four-orders less than the standard assay method. The methodology
reported here constitutes an innovative approach towards the determination of
FRET signals generated on paper.
PMID- 29330382
TI - SESN2 facilitates mitophagy by helping Parkin translocation through ULK1 mediated
Beclin1 phosphorylation.
AB - Mitophagy, the selective degradation of mitochondria by autophagy, is crucial for
the maintenance of healthy mitochondrial pool in cells. The critical event in
mitophagy is the translocation of cytosolic Parkin, a ubiquitin ligase, to the
surface of defective mitochondria. This study elucidates a novel role of
SESN2/Sestrin2, a stress inducible protein, in mitochondrial translocation of
PARK2/Parkin during mitophagy. The data demonstrates that SESN2 downregulation
inhibits BECN1/Beclin1 and Parkin interaction, thereby preventing optimum
mitochondrial accumulation of Parkin. SESN2 interacts with ULK1 (unc-51 like
kinase 1) and assists ULK1 mediated phosphorylation of Beclin1 at serine-14
position required for binding with Parkin prior to mitochondrial translocation.
The trigger for SESN2 activation and regulation of Parkin translocation is the
generation of mitochondrial superoxide. Scavenging of mitochondrial superoxide
lower the levels of SESN2, resulting in retardation of Parkin translocation.
Importantly, we observe that SESN2 mediated cytosolic interaction of Parkin and
Beclin1 is PINK1 independent but mitochondrial translocation of Parkin is PINK1
dependent. Together, these findings suggest the role of SESN2 as a positive
regulator of Parkin mediated mitophagy.
PMID- 29330384
TI - Detection of Apparent Cell-free M. tuberculosis DNA from Plasma.
AB - New diagnostics are needed to improve clinicians' ability to detect tuberculosis
(TB) disease in key populations such as children and persons living with HIV and
to rapidly detect drug resistance. Circulating cell-free DNA (ccfDNA) in plasma
is a diagnostic target in new obstetric and oncologic applications, but its
utility for diagnosing TB is not known. Here we show that Mycobacterium
tuberculosis complex DNA can be detected in plasma of persons with sputum smear
positive TB, even in the absence of mycobacteremia. Among 40 participants with
bacteriologically-confirmed smear-positive TB disease who had plasma tested by
quantitative PCR (qPCR), 18/40 (45%) had a positive result on at least one
triplicate reaction. Our results suggest that plasma DNA may be a useful target
for improving clinicians' ability to diagnose TB. We anticipate these findings to
be the starting point for optimized methods of TB ccfDNA testing and sequence
based diagnostic applications such as molecular detection of drug resistance.
PMID- 29330385
TI - Docking, thermodynamics and molecular dynamics (MD) studies of a non-canonical
protease inhibitor, MP-4, from Mucuna pruriens.
AB - Sequence and structural homology suggests that MP-4 protein from Mucuna pruriens
belongs to Kunitz-type protease inhibitor family. However, biochemical assays
showed that this protein is a poor inhibitor of trypsin. To understand the basis
of observed poor inhibition, thermodynamics and molecular dynamics (MD)
simulation studies on binding of MP-4 to trypsin were carried out. Molecular
dynamics simulations revealed that temperature influences the spectrum of
conformations adopted by the loop regions in the MP-4 structure. At an optimal
temperature, MP-4 achieves maximal binding while above and below the optimum
temperature, its functional activity is hampered due to unfavourable flexibility
and relative rigidity, respectively. The low activity at normal temperature is
due to the widening of the conformational spectrum of the Reactive Site Loop
(RSL) that reduces the probability of formation of stabilizing contacts with
trypsin. The unique sequence of the RSL enhances flexibility at ambient
temperature and thus reduces its ability to inhibit trypsin. This study shows
that temperature influences the function of a protein through modulation in the
structure of functional domain of the protein. Modulation of function through
appearance of new sequences that are more sensitive to temperature may be a
general strategy for evolution of new proteins.
PMID- 29330387
TI - Intravesical cidofovir application in BK virus cystitis after allogeneic
hematopoetic stem cell transplantation (HSCT) is safe and highly effective.
PMID- 29330383
TI - Development of a PET radioligand for potassium channels to image CNS
demyelination.
AB - Central nervous system (CNS) demyelination represents the pathological hallmark
of multiple sclerosis (MS) and contributes to other neurological conditions.
Quantitative and specific imaging of demyelination would thus provide critical
clinical insight. Here, we investigated the possibility of targeting axonal
potassium channels to image demyelination by positron emission tomography (PET).
These channels, which normally reside beneath the myelin sheath, become exposed
upon demyelination and are the target of the MS drug, 4-aminopyridine (4-AP). We
demonstrate using autoradiography that 4-AP has higher binding in non-myelinated
and demyelinated versus well-myelinated CNS regions, and describe a fluorine
containing derivative, 3-F-4-AP, that has similar pharmacological properties and
can be labeled with 18F for PET imaging. Additionally, we demonstrate that [18F]3
F-4-AP can be used to detect demyelination in rodents by PET. Further evaluation
in Rhesus macaques shows higher binding in non-myelinated versus myelinated areas
and excellent properties for brain imaging. Together, these data indicate that
[18F]3-F-4-AP may be a valuable PET tracer for detecting CNS demyelination
noninvasively.
PMID- 29330388
TI - Donor HSCs with a preexisting ASXL1-mutation led to the development of FLT3-ITD
positive AML in the donor and FLT3-ITD negative AML in the recipient after
unrelated transplant.
PMID- 29330389
TI - Accuracy and usability of the eGVHD app in assessing the severity of graft-versus
host disease at the 2017 EBMT annual congress.
PMID- 29330386
TI - On the detection of cerebral metabolic depression in experimental traumatic brain
injury using Chemical Exchange Saturation Transfer (CEST)-weighted MRI.
AB - Metabolic abnormalities are commonly observed in traumatic brain injury (TBI)
patients exhibiting long-term neurological deficits. This study investigated the
feasibility and reproducibility of using chemical exchange saturation transfer
(CEST) MRI to detect cerebral metabolic depression in experimental TBI. Phantom
and in vivo CEST experiments were conducted at 9.4 Tesla to optimize the
selective saturation for enhancing the endogenous contrast-weighting of the
proton exchanges over the range of glucose proton chemical shifts (glucoCEST) in
the resting rat brain. The optimized glucoCEST-weighted imaging was performed on
a closed-head model of diffuse TBI in rats with 2-deoxy-D-[14C]-glucose (2DG)
autoradiography validation. The results demonstrated that saturation duration of
1-2 seconds at pulse powers 1.5-2uT resulted in an improved contrast-to-noise
ratio between the gray and white matter comparable to 2DG autoradiographs. The
intrasubject (n = 4) and intersubject (n = 3) coefficient of variations for
repeated glucoCEST acquisitions (n = 4) ranged between 8-16%. Optimization for
the TBI study revealed that glucoCEST-weighted images with 1.5MUT power and 1 s
saturation duration revealed the greatest changes in contrast before and after
TBI, and positively correlated with 2DG autoradiograph (r = 0.78, p < 0.01, n =
6) observations. These results demonstrate that glucoCEST-weighted imaging may be
useful in detecting metabolic abnormalities following TBI.
PMID- 29330390
TI - Freezing the graft is not necessary for autotransplants for plasma cell myeloma
and lymphomas.
AB - We studied rates of granulocyte and platelets recovery in 359 consecutive
subjects receiving blood cell infusions in the context of autotransplants for
plasma cell myeloma (N = 216) and lymphomas (N = 143). Blood cells were mobilised
with filgrastim given for 4-5 days and collected after a median of 2 (range, 1-2)
apheresis. Apheresis products were stored at 4 degrees C for a median of 3 days
(range, 2-6 days). Most subjects received carmustine, etoposide, cytarabine and
melphalan (BEAM), cyclophosphamide, carmustine and etoposide (CBV) or high-dose
melphalan. Filgrastim was given post transplant to 319 subjects. Median numbers
of mononuclear cells collected was 31 * 10E + 6/kg (interquartile range (IQR) 37
* 10E + 6 cells/kg). Median numbers of CD34-positive cells collected was 3.6 *
10E + 6/kg (IQR 3.8 * 10E + 6/Kg). Median viability after collection was 90% (IQR
7%) after storage, 88% (IQR 12%). A total of 255 of 256 evaluable subjects
recovered bone marrow function and there was no late bone marrow failure. Median
interval to neutrophils >0.5 * E + 9/L was 13 days (range, 9-39 days) and to
platelets >20 * 10E + 9/L, 16 days (range, 7-83 days). These rates and ranges
seem comparable to those reported after autotransplants of frozen blood cells.
There was no correlation between numbers of storage days at 4 degrees C and
viability afte storage (r = -0.018, p = 0.14)) nor rates of recovery of
neutrophils (r = -0.054, p = 0.52) or platelets (r = 0.116, p = 0.14). Blood
cells collected for autotransplant can be stored at 4 degrees C for 6 d. This
method is simple, inexpensive and widely applicable.
PMID- 29330391
TI - Impact of antithymocyte globulin doses in reduced intensity conditioning before
allogeneic transplantation from matched sibling donor for patients with acute
myeloid leukemia: a report from the acute leukemia working party of European
group of Bone Marrow Transplantation.
AB - Antithymocyte globulin (ATG) is commonly used for graft-vs.-host disease (GVHD)
prophylaxis in unrelated donor allogeneic transplantation (Allo-HSCT). However,
its use is still controversial in matched sibling donor (MSD) Allo-HSCT, notably
after reduced intensity conditioning (RIC). ATG dose may influence the outcome,
explaining in part the discordant conclusions in MSD Allo-HSCT. We, therefore,
analyzed the impact of ATG doses in patients with acute myeloid leukemia in first
complete remission undergoing RIC Allo-HSCT from a MSD. We analyzed 234 patients
from the EBMT registry and compared outcome according to given ATG dose (high
dose: >= 6 mg/kg, n = 39 or low dose: < 6 mg/kg, n = 195). No difference was
found in the cumulative incidence of acute (grade 2-4: high dose vs. low dose:
21% vs. 13%, p = 0.334; adjusted hazard ratio (HR): 1.20, p = 0.712) and chronic
GVHD (extensive: high dose vs. low dose: 19% vs. 18%, p = 0.897; adjusted HR:
1.01, p = 0.980). In contrast, high dose of ATG significantly increased the
incidence of relapse (52% vs. 26%, p = 0.011; adjusted HR: 1.31, p = 0.001)
leading to impaired outcome (HR progression-free survival (PFS): 1.23, p = 0.002;
HR overall survival (OS): 1.17, p = 0.029; HR GVHD and relapse-free survival
(GRFS): 1.20, p = 0.005). We conclude that an ATG dose <6 mg/kg is sufficient for
GVHD prophylaxis, while higher doses impair disease control and outcome.
PMID- 29330392
TI - Haploidentical hematopoietic SCT using helical tomotherapy for total-body
irradiation and targeted dose boost in patients with high-risk/refractory acute
lymphoblastic leukemia.
AB - A novel conditioning regimen using helical tomotherapy (HT) was developed to
deliver 10 Gy for total body irradiation (TBI) and simultaneously augment dose to
12 Gy for targeted dose boost to total marrow, central nervous system leukemia,
and extramedullary disease sites in patients with high-risk or
relapsed/refractory acute lymphoblastic leukemia (ALL) receiving haploidentical
allogeneic hematopoietic stem cell transplantation (allo-HSCT). Fourteen patients
were included, eight of these patients were in first complete remission (CR1),
one was in CR2, one had a partial response and four patients had refractory
disease at transplantation. The median delivered average dose was 11.395 Gy
(range 10.06-12.17). The median planning target volume D95 was 8.2 Gy (range 7.52
9.01). The median delivered dose to skeleton bone with active bone marrow sites
was 12.685 Gy (range 11.12-13.52). The results of this trial suggest that using
HT TBI confers satisfactory immunosuppression and excellent eradication of
malignant cells in patients with high-risk ALL undergoing allo-HSCT, especially
in those with refractory ALL. After a median follow-up of 14.6 months (range 4
28), four patients experienced non-relapse mortality, ten patients are alive in
durable CR including remission of extramedullary leukemic infiltration. One-year
overall survival and disease-free survival rates post-transplantation were both
70.7%.
PMID- 29330393
TI - Haploidentical bone marrow transplantation with post transplant cyclophosphamide
for patients with X-linked adrenoleukodystrophy: a suitable choice in an urgent
situation.
AB - Allogeneic hematopoietic stem cell transplantation (HSCT) is the only treatment
that enhances survival and stabilizes neurologic symptoms in X-linked
adrenoleukodystrophy (X-ALD) with cerebral involvement, a severe demyelinating
disease of childhood. Patients with X-ALD who lack a well-matched HLA donor need
a rapid alternative. Haploidentical HSCT using post transplant cyclophosphamide
(PT/Cy) has been performed in patients with malignant and nonmalignant diseases
showing similar outcomes compared to other alternative sources. We describe the
outcomes of transplants performed for nine X-ALD patients using haploidentical
donors and PT/Cy. Patients received conditioning regimen with fludarabine 150
mg/m2, cyclophosphamide 29 mg/kg and 2 Gy total body irradiation (TBI) with or
without antithymocyte globulin. Graft-vs.-host disease prophylaxis consisted of
cyclophosphamide 50 mg/kg/day on days +3 and +4, tacrolimus or cyclosporine A and
mycophenolate mofetil. One patient had a primary graft failure and was not
eligible for a second transplant. Three patients had secondary graft failure and
were successfully rescued with second haploidentical transplants. Trying to
improve engraftment, conditioning regimen was changed, substituting 2 Gy TBI for
4 Gy total lymphoid irradiation. Eight patients are alive and engrafted (17-37
months after transplant). Haploidentical HSCT with PT/Cy is a feasible
alternative for X-ALD patients lacking a suitable matched donor. Graft failure
has to be addressed in further studies.
PMID- 29330394
TI - Impact of pretransplant leukemic blast% in bone marrow and peripheral blood on
transplantation outcomes of patients with acute myeloid leukemia undergoing
allogeneic stem cell transplantation in non-CR.
PMID- 29330395
TI - Predicting failure of hematopoietic stem cell mobilization before it starts: the
predicted poor mobilizer (pPM) score.
AB - Predicting mobilization failure before it starts may enable patient-tailored
strategies. Although consensus criteria for predicted PM (pPM) are available,
their predictive performance has never been measured on real data. We
retrospectively collected and analyzed 1318 mobilization procedures performed for
MM and lymphoma patients in the plerixafor era. In our sample, 180/1318 (13.7%)
were PM. The score resulting from published pPM criteria had sufficient
performance for predicting PM, as measured by AUC (0.67, 95%CI: 0.63-0.72). We
developed a new prediction model from multivariate analysis whose score (pPM
score) resulted in better AUC (0.80, 95%CI: 0.76-0.84, p < 0001). pPM-score
included as risk factors: increasing age, diagnosis of NHL, positive bone marrow
biopsy or cytopenias before mobilization, previous mobilization failure, priming
strategy with G-CSF alone, or without upfront plerixafor. A simplified version of
pPM-score was categorized using a cut-off to maximize positive likelihood ratio
(15.7, 95%CI: 9.9-24.8); specificity was 98% (95%CI: 97-98.7%), sensitivity 31.7%
(95%CI: 24.9-39%); positive predictive value in our sample was 71.3% (95%CI: 60
80.8%). Simplified pPM-score can "rule in" patients at very high risk for PM
before starting mobilization, allowing changes in clinical management, such as
choice of alternative priming strategies, to avoid highly likely mobilization
failure.
PMID- 29330396
TI - Comparable survival using a CMV-matched or a mismatched donor for CMV+ patients
undergoing T-replete haplo-HSCT with PT-Cy for acute leukemia: a study of behalf
of the infectious diseases and acute leukemia working parties of the EBMT.
AB - The role of donor CMV serostatus in the setting of non T-cell depleted haplo-HSCT
with post-transplant cyclophosphamide (PT-Cy) has not been specifically addressed
so far. Here we analyzed the impact of the donor CMV serological status on the
outcome of 983 CMV seropositive (CMV+), acute leukemia patients receiving a
first, non T-cell depleted haplo-HSCT registered in the EBMT database. The 1-year
NRM was 21.3% (95% CI: 18.4-24.8) and 18.8% (95% CI: 13.8-25.5) in the CMV D+/R+
and D-/R+ pairs, respectively (p = 0.40). Similarly, 1-year OS was 55.1% (95% CI:
50.1-58.0) and 55.7% (95% CI: 48.0-62.8) in the same groups (p = 0.50). The other
main outcomes were comparable. No difference in NRM nor OS was observed after
stratification for the intensity of conditioning and multivariate anaysis
confirmed the lack of significant association with NRM or OS. In conclusion, the
choice of a CMV-seronegative donor did not impair early survival of CMV
seropositive patients with acute leukemia after a first, non T-cell depleted
haploidentical HSCT and PT-Cy among this series of 983 consecutive patients.
Future research may focus on the assessment of the hierarchy of all the donor
variables.
PMID- 29330397
TI - Safety and efficacy of haploidentical stem cell transplantation for multiple
myeloma.
PMID- 29330398
TI - Management of important adverse events associated with inotuzumab ozogamicin:
expert panel review.
PMID- 29330399
TI - Geriatric assessment and quality of life in older patients considered for
allogeneic hematopoietic cell transplantation: a prospective risk factor and
serial assessment analysis.
AB - Allogeneic hematopoietic cell transplantation (alloHCT) in older patients
requires the weighing of risks and benefits for this potentially curative
treatment while facing age-related limitations. Comprehensive geriatric and
quality of life (EORTC QLQ C-30) assessements (CGA/QOL) in addition to disease
specific data were obtained in 108 consecutive patients (>=60 years) pre-HCT, at
day +30, +100, and +180. Median follow-up of 106 patients alive at alloHCT was
43.5 months, median age 66 years (range 60-78). Eighty-six (81.2%) had advanced
disease risk at HCT and 99 (91.7%) patients received reduced intensity
conditioning (RIC). Median PFS was 13.4 months with 38.3% (95% CI: 28.6-47.4)
alive and in remission at 2 years; median OS was 15.6 months with 43.9% (95% CI:
34.3-53.4) alive at 2 years. Prognostic factors for PFS were: age: HR 1.084 (95%
CI: 1.032-1.137, p = 0.0011); HCT-CI: HR 1.13 (95% CI: 1.001-1.274, p = 0.048);
for OS: age: HR 1.08 (95% CI: 1.031-1.139, p = 0.0017), Karnofsky Index: HR 0.97
(95% CI: 0.954-0.996, p = 0.02); EORTC QLQ C-30 fatigue: HR 1.09 (95% CI: 1.004
1.185, p = 0.039); Up-and-Go: HR 3.26 (95% CI: 1.001-10.6, p = 0.049). Follow-up
assessments as time-dependent covariates were highly prognostic for OS and PFS.
CGA/QOL confer additional prognostic utility in older alloHCT recipients.
PMID- 29330400
TI - Acute kidney injury following haplo stem cell transplantation: incidence, risk
factors and outcome.
PMID- 29330401
TI - Successful management of concurrent acquired hemophilia A and a lupus
anticoagulant in a pediatric hematopoietic stem cell transplant patient.
PMID- 29330402
TI - Chronic graft-versus-host disease features in double unit cord blood
transplantation according to National Institutes of Health 2005 cGVHD Consensus
criteria.
PMID- 29330403
TI - Ruxolitinib in steroid-refractory chronic graft-versus-host disease: experience
of a single center.
PMID- 29330404
TI - Association analysis between SUFU polymorphism rs17114808 and acute graft versus
host disease after hematopoietic stem cell transplantation.
PMID- 29330405
TI - Better outcome with haploidentical over HLA-matched related donors in patients
with Hodgkin's lymphoma undergoing allogeneic haematopoietic cell transplantation
a study by the Francophone Society of Bone Marrow Transplantation and Cellular
Therapy.
AB - The question of the best donor type between haploidentical (HAPLO) and matched
related donors (MRD) for patients with advanced HL receiving an allogeneic
hematopoietic cell transplantation (allo-HCT) is still debated. Given the lack of
data comparing these two types of donor in the setting of non-myeloablative (NMA)
or reduced-intensity (RIC) allo-HCT, we performed a multicentre retrospective
study using graft-vs.-host disease-free relapse-free survival (GRFS) as our
primary endpoint. We analysed the data of 151 consecutive HL patients who
underwent NMA or RIC allo-HCT from a HAPLO (N = 61) or MRD (N = 90) between
January 2011 and January 2016. GRFS was defined as the probability of being alive
without evidence of relapse, grade 3-4 acute GVHD or chronic GVHD. In
multivariable analysis, MRD donors were independently associated with lower GRFS
compared to HAPLO donors (HR = 2.95, P < 0.001). Disease status at transplant
other than CR was also associated with lower GRFS in multivariable analysis (HR
= 1.74, P = 0.01). In addition, the administration of ATG was independently
linked to higher GRFS (HR = 0.52, P = 0.009). In summary, we observed
significantly higher GRFS in HL patients receiving an allo-HCT using the HAPLO PT
Cy platform compared to MRD.
PMID- 29330406
TI - Adjuvant role of SeptiFast to improve the diagnosis of sepsis in a large cohort
of hematological patients.
AB - Febrile neutropenia and sepsis are common and life-threatening complications in
hematological diseases. This study was performed retrospectively in 514 patients
treated for febrile neutropenia at our institute, to investigate the clinical
usefulness of a molecular tool, LightCycler(r) SeptiFast test (SF), to promptly
recognize pathogens causing sepsis in hematological patients. We collected 1837
blood samples of 514 consecutive hematological patients. The time of processing
is short. Overall, 757 microorganisms in 663 episodes were detected by molecular
test and standard blood cultures (BC): 73.6% Gram-positive bacteria, 23.9% Gram
negative bacteria, and 2.5% fungal species. This large analysis demonstrated a
significant episode-to episode agreement (71.9%) between the two methods, higher
in negative samples (89.14%), and a specificity of 75.89%. Clinical variables
that gave a statistically significant contribution to their concordance were
absolute neutrophil count, ongoing antimicrobial therapy, timing of test
execution, and organ localization of infection. The large analysis highlights the
potential of molecular-based assays directly performed on blood samples,
especially if implementing the detection of antibiotic resistance genes, which
was lacking in the used study.
PMID- 29330407
TI - Multiscale and luminescent, hollow microspheres for gas phase thermometry.
AB - Recently developed laser-based measurement techniques are used to image the
temperatures and velocities in gas flows. They require new phosphor materials
with an unprecedented combination of properties. A novel synthesis procedure is
described here; it results in hierarchically structured, hollow microspheres of
Eu3+-doped Y2O3, with unusual particle sizes and very good characteristics
compared to full particles. Solution-based precipitation on polymer microballoons
produces very stable and luminescent, ceramic materials of extremely low density.
As a result of the - compared to established template-directed syntheses -
reduced mass of polymer that is lost upon calcination, micron-sized particles are
obtained with mesoporous walls, low defect concentrations, and nanoscale wall
thicknesses. They can be produced with larger diameters (~25 um) compared to
known hollow spheres and exhibit an optimized flow behavior. Their temperature
sensing properties and excellent fluidic follow-up behavior are shown by
determining emission intensity ratios in a specially designed heating chamber.
Emission spectroscopy and imaging, electron microscopy and X-ray diffraction
results are presented for aerosolizable Y2O3 with an optimized dopant
concentration (8%). Challenges in the field of thermofluids can be addressed by
combined application of thermometry and particle image velocimetry with such
hollow microparticles.
PMID- 29330408
TI - Collagen Type 1 Accelerates Healing of Ruptured Fetal Membranes.
AB - Preterm premature rupture of membranes (pPROM) is a major cause of preterm birth.
Recently, extracellular matrix-directed treatment is applied for wound healing.
Here, we used a pregnant mouse model to test the efficacy of collagen type 1 gel
for healing of the prematurely ruptured fetal membranes. Although injection of
PBS into the ruptured fetal membranes resulted in 40% closure, injection of
collagen type 1 improved closure rates to 90% within 72 h. Macrophages of the M2
wound healing phenotype were entrapped in the collagen layer. In primary human
amnion mesenchymal cells, collagen type 1 gels activated collagen receptor
discoidin domain receptor 2 (DDR2) to induce myosin light chain phosphorylation
and migration of injured amnion mesenchymal cells. These findings define the
mechanisms for matrix-directed therapeutics for pPROM.
PMID- 29330409
TI - Induction of ferroptosis and mitochondrial dysfunction by oxidative stress in
PC12 cells.
AB - Neurodegenerative diseases (NDD) are typically associated with neuron loss in
nervous system areas. Interventions with related death mechanisms may ameliorate
NDD progression. Oxidative stress plays an important role in NDD cell death
routines. However, tert-butylhydroperoxide (t-BHP), a widely used oxidative
stress stimulus, induces neural cell death through a mechanism that remains
elusive. In our study, the ferroptosis marker events occurred after co-treatment
with 100 MUM t-BHP for 1 h, all of which were reversed in the presence of the
ferroptosis inhibitor ferrostatin-1 (Fer-1) and the iron chelator deferoxamine,
implying the occurrence of ferroptosis. Moreover, mitochondrial dysfunction
accompanied by a decreased in membrane potential and ATP production, increased
mitochondrial ROS generation. Furthermore, this mitochondrial dysfunction could
be reversed by Fer-1. In addition, JNK1/2 and ERK1/2 were activated upstream of
the ferroptosis and mitochondrial dysfunction. In summary, these data suggest
that ferroptosis, coupled with mitochondrial dysfunction, was involved in t-BHP
induced PC12 death. JNK1/2 and ERK1/2 played important roles in t-BHP-induced
cell death. Overall, this study might provide clues to the oxidative stress-based
strategies for cell protection in NDD.
PMID- 29330411
TI - X-ray-induced Scintillation Governed by Energy Transfer Process in Glasses.
AB - The efficiency of X-ray-induced scintillation in glasses roughly depends on both
the effective atomic number Zeff and the photoluminescence quantum efficiency
Qeff of glass, which are useful tools for searching high-performance phosphors.
Here, we demonstrate that the energy transfer from host to activators is also an
important factor for attaining high scintillation efficiency in Ce-doped oxide
glasses. The scintillation intensity of glasses with coexisting fractions of Ce3+
and Ce4+ species is found to be higher than that of a pure-Ce3+-containing glass
with a lower Zeff value. Values of total attenuation of each sample indicate that
there is a non-linear correlation between the scintillation intensity and the
product of total attenuation and Qeff. The obtained results illustrate the
difficulty in understanding the luminescence induced by ionizing radiation,
including the energy absorption and subsequent energy transfer. Our findings may
provide a new approach for synthesizing novel scintillators by tailoring the
local structure.
PMID- 29330410
TI - The Impact of COMT and Childhood Maltreatment on Suicidal Behaviour in Affective
Disorders.
AB - The inconsistent findings on the association between COMT (catecholamine-O-methyl
transferase) and suicidal behaviour gave reason to choose a clear phenotype
description of suicidal behaviour and take childhood maltreatment as
environmental factor into account. The aim of this candidate-gene-association
study was to eliminate heterogeneity within the sample by only recruiting
affective disorder patients and find associations between COMT polymorphisms and
defined suicidal phenotypes. In a sample of 258 affective disorder patients a
detailed clinical assessment (e.g. CTQ, SCAN, HAMD, SBQ-R, VI-SURIAS, LPC) was
performed. DNA of peripheral blood samples was genotyped using TaqMan(r) SNP
Genotyping Assays. We observed that the haplotype GAT of rs737865, rs6269, rs4633
is significantly associated with suicide attempt (p = 0.003 [pcorr = 0.021]), and
that there is a tendency towards self-harming behaviour (p = 0.02 [pcorr = 0.08])
and also NSSI (p = 0.03 [pcorr = 0.08]), though the p values did not resist
multiple testing correction. The same effect we observed with the 4-marker slide
window haplotype, GATA of rs737865, rs6269, rs4633, rs4680 (p = 0.009 [pcorr =
0.045]). The findings support an association between the COMT gene and suicidal
behaviour phenotypes with and without childhood maltreatment as environmental
factor.
PMID- 29330412
TI - High expression of Endogenous Retroviruses from intrauterine life to adulthood in
two mouse models of Autism Spectrum Disorders.
AB - Retroelements, such as Human Endogenous Retroviruses (HERVs), have been
implicated in many complex diseases, including neurological and neuropsychiatric
disorders. Previously, we demonstrated a distinctive expression profile of
specific HERV families in peripheral blood mononuclear cells from Autistic
Spectrum Disorders (ASD) patients, suggesting their involvement in ASD. Here we
used two distinct ASD mouse models: inbred BTBR T+tf/J mice and CD-1 outbred mice
prenatally exposed to valproic acid. Whole embryos, blood and brain samples from
the offspring were collected at different ages and the expression of several ERV
families (ETnI, ETnII-alpha, ETnII-beta, ETnII-gamma, MusD and IAP),
proinflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) and Toll-like receptors
(TLR3 and TLR4) was assessed. In the two distinct mouse models analysed, the
transcriptional activity of the ERV families was significant higher in comparison
with corresponding controls, in whole embryos, blood and brain samples. Also the
expression levels of the proinflammatory cytokines and TLRs were significantly
higher than controls. Current results are in agreement with our previous findings
in ASD children, supporting the hypothesis that ERVs may serve as biomarkers of
atypical brain development. Moreover, the changes in ERVs and proinflammatory
cytokines expression could be related with the autistic-like traits acquisition
in the two mouse models.
PMID- 29330413
TI - Nerve wrap after end-to-end and tension-free neurorrhaphy attenuates neuropathic
pain: A prospective study based on cohorts of digit replantation.
AB - The repair of injured peripheral nerve is still challenging for surgeons. The end
to-end and tension-free neurorrhaphy is the current gold standard for
reconstruction after complete nerve transection without significant defect. The
main objective of this study neurorrhaphy in digit replantation affects the
sensory recovery and neuropathic pain in replanted digit. Total 101 patients who
received replantation of single completely amputated digit were included for
analysis in this study. In group I (n = 49), the digital nerves were repaired
with end-to-end and tension-free neurorrhaphy and then wrapped into a tendon
derived collagen nerve conduit. In group II (n = 52), the digital nerves were
repaired with end-to-end and tension-free neurorrhaphy only. The static two-point
discrimination (s2PD) was performed to evaluate sensory recovery. Visual analog
scale (VAS) scores of pain at rest and with exertion were measured respectively.
The s2PD tests at three and six months after surgery did not show any significant
difference between the two groups. The VAS scores at rest and with exertion of
group I were significantly reduced compared with those of group II at three and
six months after surgery. Thus, we concluded that nerve wrap into a collagen
conduit after end-to-end and tension-free neurorrhaphy could attenuate
neuropathic pain after digit replantation but have no benefit for sensory
recovery.
PMID- 29330414
TI - Partially oxidized polyvinyl alcohol conduitfor peripheral nerve regeneration.
AB - Surgical reconstruction of peripheral nerves injuries with wide substance-loss is
still a challenge. Many studies focused on the development of artificial nerve
conduits made of synthetic or biological materials but the ideal device has not
yet been identified. Here, we manufactured a conduit for peripheral nerve
regeneration using a novel biodegradable hydrogel we patented that is oxidized
polyvinyl alcohol (OxPVA). Thus, its characteristics were compared with neat
polyvinyl alcohol (PVA) and silk-fibroin (SF) conduits, through in vitro and in
vivo analysis. Unlike SF, OxPVA and neat PVA scaffolds did not support SH-SY5Y
adhesion and proliferation in vitro. After implantation in rat model of sciatic
nerve transection, the three conduits sustained the regeneration of the injured
nerve filling a gap of 5 mm in 12 weeks. Implanted animals showed a good gait
recovery. Morphometric data related to the central portion of the explanted
conduit interestingly highlighted a significantly better outcome for OxPVA
scaffolds compared to PVA conduits in terms of axon density, also with respect to
the autograft group. This study suggests the potential of our novel biomaterial
for the development of conduits for clinical use in case of peripheral nerve
lesions with substance loss.
PMID- 29330415
TI - Unusual multiscale mechanics of biomimetic nanoparticle hydrogels.
AB - Viscoelastic properties are central for gels and other materials. Simultaneously,
high storage and loss moduli are difficult to attain due to their contrarian
requirements to chemical structure. Biomimetic inorganic nanoparticles offer a
promising toolbox for multiscale engineering of gel mechanics, but a conceptual
framework for their molecular, nanoscale, mesoscale, and microscale engineering
as viscoelastic materials is absent. Here we show nanoparticle gels with
simultaneously high storage and loss moduli from CdTe nanoparticles. Viscoelastic
figure of merit reaches 1.83 MPa exceeding that of comparable gels by 100-1000
times for glutathione-stabilized nanoparticles. The gels made from the smallest
nanoparticles display the highest stiffness, which was attributed to the drastic
change of GSH configurations when nanoparticles decrease in size. A computational
model accounting for the difference in nanoparticle interactions for variable GSH
configurations describes the unusual trends of nanoparticle gel viscoelasticity.
These observations are generalizable to other NP gels interconnected by
supramolecular interactions and lead to materials with high-load bearing
abilities and energy dissipation needed for multiple technologies.
PMID- 29330416
TI - Virtual Genome Walking across the 32 Gb Ambystoma mexicanum genome; assembling
gene models and intronic sequence.
AB - Large repeat rich genomes present challenges for assembly using short read
technologies. The 32 Gb axolotl genome is estimated to contain ~19 Gb of
repetitive DNA making an assembly from short reads alone effectively impossible.
Indeed, this model species has been sequenced to 20* coverage but the reads could
not be conventionally assembled. Using an alternative strategy, we have assembled
subsets of these reads into scaffolds describing over 19,000 gene models. We call
this method Virtual Genome Walking as it locally assembles whole genome reads
based on a reference transcriptome, identifying exons and iteratively extending
them into surrounding genomic sequence. These assemblies are then linked and
refined to generate gene models including upstream and downstream genomic, and
intronic, sequence. Our assemblies are validated by comparison with previously
published axolotl bacterial artificial chromosome (BAC) sequences. Our analyses
of axolotl intron length, intron-exon structure, repeat content and synteny
provide novel insights into the genic structure of this model species. This
resource will enable new experimental approaches in axolotl, such as ChIP-Seq and
CRISPR and aid in future whole genome sequencing efforts. The assembled sequences
and annotations presented here are freely available for download from
https://tinyurl.com/y8gydc6n . The software pipeline is available from
https://github.com/LooseLab/iterassemble .
PMID- 29330417
TI - High STAP1 expression in DUX4-rearranged cases is not suitable as therapeutic
target in pediatric B-cell precursor acute lymphoblastic leukemia.
AB - Approximately 25% of the pediatric B-cell precursor acute lymphoblastic leukemia
(BCP-ALL) cases are genetically unclassified. More thorough elucidation of the
pathobiology of these genetically unclassified ('B-other') cases may identify
novel treatment options. We analyzed gene expression profiles of 572 pediatric
BCP-ALL cases, representing all major ALL subtypes. High expression of STAP1, an
adaptor protein downstream of the B-cell receptor (BCR), was identified in BCR
ABL1-like and non-BCR-ABL1-like B-other cases. Limma analysis revealed an
association between high expression of STAP1 and BCR signaling genes. However,
STAP1 expression and pre-BCR signaling were not causally related: cytoplasmic
IgMU levels were not abnormal in cases with high levels of STAP1 and stimulation
of pre-BCR signaling did not induce STAP1 expression. To elucidate the role of
STAP1 in BCP-ALL survival, expression was silenced in two human BCP-ALL cell
lines. Knockdown of STAP1 did not reduce the proliferation rate or viability of
these cells, suggesting that STAP1 is not a likely candidate for precision
medicines. Moreover, high expression of STAP1 was not predictive for an
unfavorable prognosis of BCR-ABL1-like and non-BCR-ABL1-like B-other cases.
Remarkably, DUX4-rearrangements and intragenic ERG deletions, were enriched in
cases harboring high expression of STAP1.
PMID- 29330418
TI - HLA-B, HLA-C and KIR improve the predictive value of IFNL3 for Hepatitis C
spontaneous clearance.
AB - IFNL3 is the strongest predictor of spontaneous resolution (SR) of hepatitis C
virus (HCV), however, consideration of IFNL3 genotype alone is of limited
clinical value for the prediction of SR or chronic HCV infection. The objective
of this study was to analyze the impact of HLA-B, HLA-C and KIRs on SR, as well
as their additive effects on the predictive value of the IFNL3 genotype. We
conducted a retrospective study of HIV patients that included both SR and chronic
HCV patients. In our study, 61.6% of patients with IFNL3 CC achieved SR, and
81.5% with non-CC genotypes did not achieve SR. HLA-B*44, HLA-C*12, and KIR3DS1
were identified as predictive factors for SR, with percentages of 77.4%, 85.7%
and 86.2%, respectively, for patients who did not experience SR. The presence of
at least one of these three markers, defined as a genetically unfavorable profile
(GUP), combined with the IFNL3 non-CC genotype showed a value of 100% for non-SR.
The absence of the three markers, defined as a genetically favorable profile
(GFP), in addition to the IFNL3 CC genotype showed a percentage of 74.1% for SR.
The combination of these markers in addition to the IFNL3 genotype improves the
predictive value of IFNL3 for SR of acute HCV infection in HIV patients, which
would be clinically valuable.
PMID- 29330419
TI - Parkinson disease with constipation: clinical features and relevant factors.
AB - Constipation is one of the most frequent non-motor symptoms of Parkinson disease
(PD) and it may be ignored by PD patients, leading to this problem not to be
reported in time. The relationships between constipation and demographic
variables, motor symptoms and other non-motor symptoms of PD are still unknown.
PD patients were evaluated by diagnostic criteria of functional constipation in
Rome III and divided into PD with constipation (PD-C) and PD with no constipation
(PD-NC) groups. PD patients were assessed by rating scales of motor symptoms and
other non-motor symptoms, activity of daily living and quality of life. The
frequency of constipation in PD patients was 61.4%, and 24.5% of PD patients had
constipation before the onset of motor symptoms. PD-C group had older age and age
of onset, longer disease duration, more advanced disease stage, and more severe
motor symptoms and non-motor symptoms, including worse cognition and emotion,
poorer sleep quality, severer autonomic symptoms, fatigue and apathy. Binary
Logistic regression analysis showed that the age, H-Y stage, depression, anxiety
and autonomic dysfunction increased the risk of constipation in PD patients.
Constipation exerted serious impact on the activity of daily living and quality
of life in PD patients.
PMID- 29330420
TI - Left ventricular hypertrophy and cognitive function: a systematic review.
AB - Cognitive impairment is common in patients with hypertension. Left ventricular
hypertrophy (LVH) is recognised as a marker of hypertension-related organ damage
and is a strong predictor of coronary artery disease, heart failure and stroke.
There is evidence that LVH is independently associated with cognitive impairment,
even after adjustment for the presence of hypertension. We conducted a systematic
review that examined cognitive impairment in adults with LVH. Independent
searches were performed in Ovid MEDLINE, Ovid psycInfo and PubMed with the terms
left ventricular hypertrophy and cognition. Seventy-three studies were identified
when both searches were combined. After limiting the search to studies that were:
(1) reported in English; (2) conducted in humans; (3) in adults aged 50 years and
older; and (4) investigated the relationship between LVH and cognitive
performance, nine papers were included in this systematic review. The majority of
studies found an association between LVH and cognitive performance. Inspection of
results indicated that individuals with LVH exhibited a lower performance in
cognitive tests, when compared to individuals without LVH. Memory and executive
functions were the cognitive domains that showed a specific vulnerability to the
presence of LVH. A possible mechanism for the relationship between LVH and
cognition is the presence of cerebral white matter damage. White matter lesions
occur frequently in patients with LVH and may contribute to cognitive
dysfunction. Together, the results of this review suggest that memory impairment
and executive dysfunction are the cognitive domains that showed a particular
association with the presence of LVH.
PMID- 29330421
TI - Premature recruitment of oocyte pool and increased mTOR activity in Fmr1 knockout
mice and reversal of phenotype with rapamycin.
AB - While mutations in the fragile X mental retardation-1 (FMR1) gene are associated
with varying reproductive outcomes in females, the effects of a complete lack of
FMR1 expression are not known. Here, we studied the ovarian and reproductive
phenotypes in an Fmr1 knockout (KO) mouse model and the role of mammalian target
of rapamycin (mTOR) signaling. Breeding, histologic and mTOR signaling data were
obtained at multiple time points in KO and wild type (WT) mice fed a control or
rapamycin (mTOR inhibitor) diet. KO mice showed an earlier decline in ovarian
reserve than WT mice with an increased proportion of activated follicles. mTOR
and phosphorylated S6 kinase (p-S6K) levels, a measure of downstream mTOR
signaling, were elevated in the KO ovaries. Rapamycin blocked these effects in KO
mice, and increased the primordial follicle pool and age of last litter in WT
mice. Our data demonstrates an early decline in reproductive capacity in Fmr1 KO
mice and proposes that premature recruitment of the primordial pool via altered
mTOR signaling may be the mechanism. Reversal of phenotypes and protein levels in
rapamycin-treated KO mice, as well as increased reproductive lifespan of
rapamycin-fed WT mice, suggest the mTOR pathway as a potential therapeutic
target.
PMID- 29330422
TI - Seabirds fighting for land: phenotypic consequences of breeding area constraints
at a small remote archipelago.
AB - Identifying associations between phenotypes and environmental parameters is
crucial for understanding how natural selection acts at the individual level. In
this context, genetically isolated populations can be useful models for
identifying the forces selecting fitness-related traits. Here, we use a
comprehensive dataset on a genetically and ecologically isolated population of
the strictly marine bird, the brown booby Sula leucogaster, at the tropical and
remote Saint Peter and Saint Paul Archipelago, mid-Atlantic Ocean, in order to
detect phenotypic adjustments from interindividual differences in diet, foraging
behaviour, and nest quality. For this, we took biometrics of all individuals of
the colony breeding in 2014 and 2015 and tested their associations with nest
quality, diet parameters, and foraging behaviour. While body size was not related
to the foraging parameters, the body size of the females (responsible for nest
acquisition and defence) was significantly associated with the nest quality, as
larger females occupied high-quality nests. Our findings suggest that the small
breeding area, rather than prey availability, is a limiting factor, emphasizing
the role of on-land features in shaping phenotypic characteristics and fitness in
land-dependent marine vertebrates.
PMID- 29330425
TI - Formation and dynamics of a solar eruptive flux tube.
AB - Solar eruptions are well-known drivers of extreme space weather, which can
greatly disturb the Earth's magnetosphere and ionosphere. The triggering process
and initial dynamics of these eruptions are still an area of intense study. Here
we perform a magnetohydrodynamic simulation taking into account the observed
photospheric magnetic field to reveal the dynamics of a solar eruption in a real
magnetic environment. In our simulation, we confirmed that tether-cutting
reconnection occurring locally above the polarity inversion line creates a
twisted flux tube, which is lifted into a toroidal unstable area where it loses
equilibrium, destroying the force-free state, and driving the eruption.
Consequently, a more highly twisted flux tube is built up during this initial
phase, which can be further accelerated even when it returns to a stable area. We
suggest that a nonlinear positive feedback process between the flux tube
evolution and reconnection is the key to ensure this extra acceleration.
PMID- 29330424
TI - Metagenomic and metabolomic analyses unveil dysbiosis of gut microbiota in
chronic heart failure patients.
AB - Previous studies suggested a possible gut microbiota dysbiosis in chronic heart
failure (CHF). However, direct evidence was lacking. In this study, we
investigated the composition and metabolic patterns of gut microbiota in CHF
patients to provide direct evidence and comprehensive understanding of gut
microbiota dysbiosis in CHF. We enrolled 53 CHF patients and 41 controls.
Metagenomic analyses of faecal samples and metabolomic analyses of faecal and
plasma samples were then performed. We found that the composition of gut
microbiota in CHF was significantly different from controls. Faecalibacterium
prausnitzii decrease and Ruminococcus gnavus increase were the essential
characteristics in CHF patients' gut microbiota. We also observed an imbalance of
gut microbes involved in the metabolism of protective metabolites such as
butyrate and harmful metabolites such as trimethylamine N-oxide in CHF patients.
Metabolic features of both faecal and plasma samples from CHF patients also
significantly changed. Moreover, alterations in faecal and plasma metabolic
patterns correlated with gut microbiota dysbiosis in CHF. Taken together, we
found that CHF was associated with distinct gut microbiota dysbiosis and
pinpointed the specific core bacteria imbalance in CHF, along with correlations
between changes in certain metabolites and gut microbes.
PMID- 29330423
TI - T cell immunity to Zika virus targets immunodominant epitopes that show cross
reactivity with other Flaviviruses.
AB - Zika virus (ZIKV) Infection has several outcomes from asymptomatic exposure to
rash, conjunctivitis, Guillain-Barre syndrome or congenital Zika syndrome.
Analysis of ZIKV immunity is confounded by the fact that several related
Flaviviruses infect humans, including Dengue virus 1-4, West Nile virus and
Yellow Fever virus. HLA class II restricted T cell cross-reactivity between ZIKV
and other Flaviviruses infection(s) or vaccination may contribute to protection
or to enhanced immunopathology. We mapped immunodominant, HLA class II
restricted, CD4 epitopes from ZIKV Envelope (Env), and Non-structural (NS) NS1,
NS3 and NS5 antigens in HLA class II transgenic mice. In several cases, ZIKV
primed CD4 cells responded to homologous sequences from other viruses, including
DENV1-4, WNV or YFV. However, cross-reactive responses could confer immune
deviation - the response to the Env DENV4 p1 epitope in HLA-DR1 resulted in IL
17A immunity, often associated with exacerbated immunopathogenesis. This
conservation of recognition across Flaviviruses, may encompass protective and/or
pathogenic components and poses challenges to characterization of ZIKV protective
immunity.
PMID- 29330427
TI - Three-Dimensional Speckle Light Self-Healing-Based Imaging System.
AB - Recently new methodologies for imaging have been achieved making use of multiple
light scattering. Here we present the self-healing effect using a speckled light
field. We present an experiment that constitutes a useful application for a three
dimensional light sheet-based imaging system through an inhomogeneous medium.
Each layer can be imaged independently of the others. The axial resolution
basically depends on the coherence length, which can be sub-wavelength and
controllable. This allows for a simple and direct technique for imaging through
scattering layers with axial resolution improvement. Our results may find
applications not only in bio-microscopy systems but also in data transmission.
PMID- 29330426
TI - Glucose-independent segmental phase angles from multi-frequency bioimpedance
analysis to discriminate diabetes mellitus.
AB - We investigated segmental phase angles (PAs) in the four limbs using a multi
frequency bioimpedance analysis (MF-BIA) technique for noninvasively diagnosing
diabetes mellitus. We conducted a meal tolerance test (MTT) for 45 diabetic and
45 control subjects stratified by age, sex and body mass index (BMI). HbA1c and
the waist-to-hip-circumference ratio (WHR) were measured before meal intake, and
we measured the glucose levels and MF-BIA PAs 5 times for 2 hours after meal
intake. We employed a t-test to examine the statistical significance and the area
under the curve (AUC) of the receiver operating characteristics (ROC) to test the
classification accuracy using segmental PAs at 5, 50, and 250 kHz. Segmental PAs
were independent of the HbA1c or glucose levels, or their changes caused by the
MTT. However, the segmental PAs were good indicators for noninvasively screening
diabetes In particular, leg PAs in females and arm PAs in males showed best
classification accuracy (AUC = 0.827 for males, AUC = 0.845 for females). Lastly,
we introduced the PA at maximum reactance (PAmax), which is independent of
measurement frequencies and can be obtained from any MF-BIA device using a Cole
Cole model, thus showing potential as a useful biomarker for diabetes.
PMID- 29330428
TI - Structural insights into two distinct binding modules for Lys63-linked
polyubiquitin chains in RNF168.
AB - The E3 ubiquitin (Ub) ligase RNF168 plays a critical role in the initiation of
the DNA damage response to double-strand breaks (DSBs). The recruitment of RNF168
by ubiquitylated targets involves two distinct regions, Ub-dependent DSB
recruitment module (UDM) 1 and UDM2. Here we report the crystal structures of the
complex between UDM1 and Lys63-linked diUb (K63-Ub2) and that between the C
terminally truncated UDM2 (UDM2DeltaC) and K63-Ub2. In both structures, UDM1 and
UDM2DeltaC fold as a single alpha-helix. Their simultaneous bindings to the
distal and proximal Ub moieties provide specificity for Lys63-linked Ub chains.
Structural and biochemical analyses of UDM1 elucidate an Ub-binding mechanism
between UDM1 and polyubiquitylated targets. Mutations of Ub-interacting residues
in UDM2 prevent the accumulation of RNF168 to DSB sites in U2OS cells, whereas
those in UDM1 have little effect, suggesting that the interaction of UDM2 with
ubiquitylated and polyubiquitylated targets mainly contributes to the RNF168
recruitment.
PMID- 29330429
TI - Tissue and serum microRNA profile of oral squamous cell carcinoma patients.
AB - Head and neck cancer is characterized by malignant tumors arising from the
epithelium covering the upper aerodigestive tract, and the majority of these
epithelial malignancies are squamous cell carcinomas (SCCs) of the oral cavity
(OSCCs). The aim of the current work was to identify miRNAs regulated in OSCC
cancerous tissue when compared to a healthy adjacent tissue and to verify the
presence of the same miRNAs in the circulation of these patients. For that serum
samples and biopsies of healthy and tumor tissues were collected from five
patients diagnosed with OSCC of the oral cavity, RNA was extracted from these
samples and microRNAs libraries were prepared and sequenced. A total 255 miRNAs
were identified in tissue and 381 different miRNAs were identified in serum
samples. When comparing the miRNA expression between tumor and healthy tissue we
identified 48 miRNAs (25 down- and 23 up-regulated) that were differentially
expressed (FDR < 0.05). From these 48 differentially expressed miRNAs in tissue,
30 miRNAs were also found in the serum of the same patients. hsa-miR-32-5p was up
regulated in tumor compared to healthy tissue in our study, and was previously
shown to be up-regulated in the serum of OSCC patients. Therefore, this suggests
that miRNAs can be used as potential non-invasive biomarkers of OSCC.
PMID- 29330430
TI - Carbon-doped SnS2 nanostructure as a high-efficiency solar fuel catalyst under
visible light.
AB - Photocatalytic formation of hydrocarbons using solar energy via artificial
photosynthesis is a highly desirable renewable-energy source for replacing
conventional fossil fuels. Using an L-cysteine-based hydrothermal process, here
we synthesize a carbon-doped SnS2 (SnS2-C) metal dichalcogenide nanostructure,
which exhibits a highly active and selective photocatalytic conversion of CO2 to
hydrocarbons under visible-light. The interstitial carbon doping induced
microstrain in the SnS2 lattice, resulting in different photophysical properties
as compared with undoped SnS2. This SnS2-C photocatalyst significantly enhances
the CO2 reduction activity under visible light, attaining a photochemical quantum
efficiency of above 0.7%. The SnS2-C photocatalyst represents an important
contribution towards high quantum efficiency artificial photosynthesis based on
gas phase photocatalytic CO2 reduction under visible light, where the in situ
carbon-doped SnS2 nanostructure improves the stability and the light harvesting
and charge separation efficiency, and significantly enhances the photocatalytic
activity.
PMID- 29330431
TI - Gyrotropic Zener tunneling and nonlinear IV curves in the zero-energy Landau
level of graphene in a strong magnetic field.
AB - We have investigated tunneling current through a suspended graphene Corbino disk
in high magnetic fields at the Dirac point, i.e. at filling factor nu = 0. At the
onset of the dielectric breakdown the current through the disk grows
exponentially before ohmic behaviour, but in a manner distinct from thermal
activation. We find that Zener tunneling between Landau sublevels dominates,
facilitated by tilting of the source-drain bias potential. According to our
analytic modelling, the Zener tunneling is strongly affected by the gyrotropic
force (Lorentz force) due to the high magnetic field.
PMID- 29330432
TI - Developing genome-wide SNPs and constructing an ultrahigh-density linkage map in
oil palm.
AB - Oil palm (Elaeis guineensis Jacq.) is the leading oil-producing crops and the
most important edible oil resource worldwide. DNA markers and genetic linkage
maps are essential resources for marker-assisted selection to accelerate genetic
improvement. We conducted RAD-seq on an Illumina NextSeq500 to discover genome
wide SNPs, and used the SNPs to construct a linkage map for an oil palm (Tenera)
population derived from a cross between a Deli Dura and an AVROS Pisifera. The
RAD-seq produced 1,076 million single-end reads across the breeding population
containing 155 trees. Mining this dataset detected 510,251 loci. After filtering
out loci with low accuracy and more than 20% missing data, 11,394 SNPs were
retained. Using these SNPs, in combination with 188 anchor SNPs and 123
microsatellites, we constructed a linkage map containing 10,023 markers covering
16 chromosomes. The map length is 2,938.2 cM with an average marker space of 0.29
cM. The large number of SNPs will supply ample choices of DNA markers in
analysing the genetic diversity, population structure and evolution of oil palm.
This high-density linkage map will contribute to mapping quantitative trait loci
(QTL) for important traits, thus accelerating oil palm genetic improvement.
PMID- 29330434
TI - Targeting melanoma stem cells with the Vitamin E derivative delta-tocotrienol.
AB - The prognosis of metastatic melanoma is very poor, due to the development of drug
resistance. Cancer stem cells (CSCs) may play a crucial role in this mechanism,
contributing to disease relapse. We first characterized CSCs in melanoma cell
lines. We observed that A375 (but not BLM) cells are able to form melanospheres
and show CSCs traits: expression of the pluripotency markers SOX2 and KLF4,
higher invasiveness and tumor formation capability in vivo with respect to
parental adherent cells. We also showed that a subpopulation of autofluorescent
cells expressing the ABCG2 stem cell marker is present in the A375 spheroid
culture. Based on these data, we investigated whether delta-TT might target
melanoma CSCs. We demonstrated that melanoma cells escaping the antitumor
activity of delta-TT are completely devoid of the ability to form melanospheres.
In contrast, cells that escaped vemurafenib treatment show a higher ability to
form melanospheres than control cells. delta-TT also induced disaggregation of
A375 melanospheres and reduced the spheroidogenic ability of sphere-derived
cells, reducing the expression of the ABCG2 marker. These data demonstrate that
delta-TT exerts its antitumor activity by targeting the CSC subpopulation of A375
melanoma cells and might represent a novel chemopreventive/therapeutic strategy
against melanoma.
PMID- 29330436
TI - Blood transcriptomics of captive forest musk deer (Moschus berezovskii) and
possible associations with the immune response to abscesses.
AB - Forest musk deer (Moschus berezovskii; FMD) are both economically valuable and
highly endangered. A problem for FMD captive breeding programs has been the
susceptibility of FMD to abscesses. To investigate the mechanisms of abscess
development in FMD, the blood transcriptomes of three purulent and three healthy
individuals were generated. A total of ~39.68 Gb bases were generated using
Illumina HiSeq 4000 sequencing technology and 77,752 unigenes were identified
after assembling. All the unigenes were annotated, with 63,531 (81.71%) mapping
to at least one database. Based on these functional annotations, 45,798 coding
sequences (CDS) were detected, along with 12,697 simple sequence repeats (SSRs)
and 65,536 single nucleotide polymorphisms (SNPs). A total of 113 unigenes were
found to be differentially expressed between healthy and purulent individuals.
Functional annotation indicated that most of these differentially expressed genes
were involved in the regulation of immune system processes, particularly those
associated with parasitic and bacterial infection pathways.
PMID- 29330433
TI - Effect of atorvastatin on the gut microbiota of high fat diet-induced
hypercholesterolemic rats.
AB - The aim of the present study was to investigate alterations in gut microbiota
associated with hypercholesterolemia and treatment with atorvastatin, a commonly
prescribed cholesterol-lowering drug. In this study, seven experimental groups of
rats were developed based on diets [high-fat diet (HFD) and normal chow diet
(NCD)] and various doses of atorvastatin in HFD and NCD groups. 16S rRNA amplicon
sequencing was used to analyze the gut microbiota. Atorvastatin significantly
reduced the cholesterol level in treated rats. Bacterial diversity was decreased
in the drug-treated NCD group compared to the NCD control, but atorvastatin
treated HFD groups showed a relative increase in biodiversity compared to HFD
control group. Atorvastatin promoted the relative abundance of Proteobacteria and
reduced the abundance of Firmicutes in drug-treated HFD groups. Among the
dominant taxa in the drug-treated HFD groups, Oscillospira, Parabacteroides,
Ruminococcus, unclassified CF231, YRC22 (Paraprevotellaceae), and SMB53
(Clostridiaceae) showed reversion in population distribution toward NCD group
relative to HFD group. Drug-treated HFD and NCD groups both showed an increased
relative abundance of Helicobacter. Overall, bacterial community composition was
altered, and diversity of gut microbiota increased with atorvastatin treatment in
HFD group. Reversion in relative abundance of specific dominant taxa was observed
with drug treatment to HFD rats.
PMID- 29330435
TI - Beta-catenin cleavage enhances transcriptional activation.
AB - Nuclear activation of Wnt/beta-catenin signaling is required for cell
proliferation in inflammation and cancer. Studies from our group indicate that
beta-catenin activation in colitis and colorectal cancer (CRC) correlates with
increased nuclear levels of beta-catenin phosphorylated at serine 552 (pbeta
Cat552). Biochemical analysis of nuclear extracts from cancer biopsies revealed
the existence of low molecular weight (LMW) pbeta-Cat552, increased to the
exclusion of full size (FS) forms of beta-catenin. LMW beta-catenin lacks both
termini, leaving residues in the armadillo repeat intact. Further experiments
showed that TCF4 predominantly binds LMW pbeta-Cat552 in the nucleus of inflamed
and cancerous cells. Nuclear chromatin bound localization of LMW pbeta-Cat552 was
blocked in cells by inhibition of proteasomal chymotrypsin-like activity but not
by other protease inhibitors. K48 polyubiquitinated FS and LMW beta-catenin were
increased by treatment with bortezomib. Overexpressed in vitro double truncated
beta-catenin increased transcriptional activity, cell proliferation and growth of
tumor xenografts compared to FS beta-catenin. Serine 552-> alanin substitution
abrogated K48 polyubiquitination, beta-catenin nuclear translocation and tumor
xenograft growth. These data suggest that a novel proteasome-dependent
posttranslational modification of beta-catenin enhances transcriptional
activation. Discovery of this pathway may be helpful in the development of
diagnostic and therapeutic tools in colitis and cancer.
PMID- 29330437
TI - A Computational Assay of Estrogen Receptor alpha Antagonists Reveals the Key
Common Structural Traits of Drugs Effectively Fighting Refractory Breast Cancers.
AB - Somatic mutations of the Estrogen Receptor alpha (ERalpha) occur with an up to
40% incidence in ER sensitive breast cancer (BC) patients undergoing prolonged
endocrine treatments. These polymorphisms are implicated in acquired resistance,
disease relapse, and increased mortality rates, hence representing a current
major clinical challenge. Here, multi-microseconds (12.5 us) molecular dynamics
simulations revealed that recurrent ERalpha polymorphisms (i. e. L536Q, Y537S,
Y537N, D538G) (mERalpha) are constitutively active in their apo form and that
they prompt the selection of an agonist (active)-like conformation even upon
antagonists binding. Interestingly, our simulations rationalize, for the first
time, the efficacy profile of (pre)clinically used Selective Estrogen Receptor
Modulators/Downregulators (SERMs/SERDs) against these variants, enlightening, at
atomistic level of detail, the key common structural traits needed by drugs able
to effectively fight refractory BC types. This knowledge represents a key
advancement for mechanism-based therapeutics targeting resistant ERalpha
isoforms, potentially allowing the community to move a step closer to 'precision
medicine' calibrated on patients' genetic profiles and disease progression.
PMID- 29330438
TI - Improved Resolution Optical Time Stretch Imaging Based on High Efficiency In
Fiber Diffraction.
AB - Most overlooked challenges in ultrafast optical time stretch imaging (OTSI) are
sacrificed spatial resolution and higher optical loss. These challenges are
originated from optical diffraction devices used in OTSI, which encode image into
spectra of ultrashort optical pulses. Conventional free-space diffraction
gratings, as widely used in existing OTSI systems, suffer from several inherent
drawbacks: limited diffraction efficiency in a non-Littrow configuration due to
inherent zeroth-order reflection, high coupling loss between free-space gratings
and optical fibers, bulky footprint, and more importantly, sacrificed imaging
resolution due to non-full-aperture illumination for individual wavelengths. Here
we report resolution-improved and diffraction-efficient OTSI using in-fiber
diffraction for the first time to our knowledge. The key to overcome the existing
challenges is a 45 degrees tilted fiber grating (TFG), which serves as a compact
in-fiber diffraction device offering improved diffraction efficiency (up to 97%),
inherent compatibility with optical fibers, and improved imaging resolution
owning to almost full-aperture illumination for all illumination wavelengths. 50
million frames per second imaging of fast moving object at 46 m/s with improved
imaging resolution has been demonstrated. This conceptually new in-fiber
diffraction design opens the way towards cost-effective, compact and high
resolution OTSI systems for image-based high-throughput detection and
measurement.
PMID- 29330440
TI - Evidence of s-wave superconductivity in the noncentrosymmetric La7Ir3.
AB - Superconductivity in noncentrosymmetric compounds has attracted sustained
interest in the last decades. Here we present a detailed study on the transport,
thermodynamic properties and the band structure of the noncentrosymmetric
superconductor La 7 Ir 3 (T c ~ 2.3 K) that was recently proposed to break the
time-reversal symmetry. It is found that La7Ir3 displays a moderately large
electronic heat capacity (Sommerfeld coefficient gamma n ~ 53.1 mJ/mol K2) and a
significantly enhanced Kadowaki-Woods ratio (KWR ~32 MUOmega cm mol2 K2 J-2) that
is greater than the typical value (~10 MUOmega cm mol2 K2 J-2) for strongly
correlated electron systems. The upper critical field Hc2 was seen to be nicely
described by the single-band Werthamer-Helfand-Hohenberg model down to very low
temperatures. The hydrostatic pressure effects on the superconductivity were also
investigated. The heat capacity below T c reveals a dominant s-wave gap with the
magnitude close to the BCS value. The first-principles calculations yield the
electron-phonon coupling constant lambda = 0.81 and the logarithmically averaged
frequency omega ln = 78.5 K, resulting in a theoretical T c = 2.5 K, close to
the experimental value. Our calculations suggest that the enhanced electronic
heat capacity is more likely due to electron-phonon coupling, rather than the
electron-electron correlation effects. Collectively, these results place severe
constraints on any theory of exotic superconductivity in this system.
PMID- 29330439
TI - Induction of protein citrullination and auto-antibodies production in murine
exposed to nickel nanomaterials.
AB - Citrullination, or the post-translational deimination of polypeptide-bound
arginine, is involved in several pathological processes in the body, including
autoimmunity and tumorigenesis. Recent studies have shown that nanomaterials can
trigger protein citrullination, which might constitute a common pathogenic link
to disease development. Here we demonstrated auto-antibody production in serum of
nanomaterials-treated mice. Citrullination-associated phenomena and PAD levels
were found to be elevated in nanomaterials -treated cell lines as well as in the
spleen, kidneys and lymph nodes of mice, suggesting a systemic response to
nanomaterials injection, and validated in human pleural and pericardial malignant
mesothelioma (MM) samples. The observed systemic responses in mice exposed to
nanomaterials support the evidence linking exposure to environmental factors with
the development of autoimmunity responses and reinforces the need for
comprehensive safety screening of nanomaterials. Furthermore, these nanomaterials
induce pathological processes that mimic those observed in Pleural MM, and
therefore require further investigations into their carcinogenicity.
PMID- 29330441
TI - Pathway design using de novo steps through uncharted biochemical spaces.
AB - Existing retrosynthesis tools generally traverse production routes from a source
to a sink metabolite using known enzymes or de novo steps. Generally, important
considerations such as blending known transformations with putative steps,
complexity of pathway topology, mass conservation, cofactor balance,
thermodynamic feasibility, microbial chassis selection, and cost are largely
dealt with in a posteriori fashion. The computational procedure we present here
designs bioconversion routes while simultaneously considering any combination of
the aforementioned design criteria. First, we track and codify as rules all
reaction centers using a prime factorization-based encoding technique (rePrime).
Reaction rules and known biotransformations are then simultaneously used by the
pathway design algorithm (novoStoic) to trace both metabolites and molecular
moieties through balanced bio-conversion strategies. We demonstrate the use of
novoStoic in bypassing steps in existing pathways through putative
transformations, assembling complex pathways blending both known and putative
steps toward pharmaceuticals, and postulating ways to biodegrade xenobiotics.
PMID- 29330442
TI - Competition among the attentional networks due to resource reduction in Tibetan
indigenous residents: evidence from event-related potentials.
AB - This study used the attention network test (ANT) to evaluate the alerting,
orienting, and executive network efficiencies of attention related to indigenous
residents who were born and raised until early adulthood in different high
altitude areas (2900-m, 3700-m, and 4200-m) at the same location (3700-m) where
these residents had been living for approximately 2 years in Tibet. We further
applied the event-related potential (ERP) method to identify the underlying
neurophysiological basis. Based on the ANT, we found that, in the 4200-m
residents, executive function was increased but the orienting function was
decreased, and the executive and orienting network scores were oppositely
correlated. The behavioral findings were supported by the ERP data, showing that
the P3 amplitude changes indicated that the executive function was over-active
under conflict conditions and that the N1 amplitude change indicated a decreased
orienting function in the 4200-m residents. In addition, the changed P3
amplitudes were significantly correlated with intelligence performance across the
residents only in the 4200-m group. The present study provided evidence for
competition among the attentional networks due to high-altitude exposure in
indigenous residents, and showed the existence of a threshold of the influence of
high altitudes on attentional function in the brain.
PMID- 29330443
TI - An insight into intestinal mucosal microbiota disruption after stroke.
AB - Recent work from our laboratory has provided evidence that indicates selective
bacterial translocation from the host gut microbiota to peripheral tissues (i.e.
lung) plays a key role in the development of post-stroke infections. Despite
this, it is currently unknown whether mucosal bacteria that live on and interact
closely with the host intestinal epithelium contribute in regulating bacterial
translocation after stroke. Here, we found that the microbial communities within
the mucosa of gastrointestinal tract (GIT) were significantly different between
sham-operated and post-stroke mice at 24 h following surgery. The differences in
microbiota composition were substantial in all sections of the GIT and were
significant, even at the phylum level. The main characteristics of the stroke
induced shift in mucosal microbiota composition were an increased abundance of
Akkermansia muciniphila and an excessive abundance of clostridial species.
Furthermore, we analysed the predicted functional potential of the altered
mucosal microbiota induced by stroke using PICRUSt and revealed significant
increases in functions associated with infectious diseases, membrane transport
and xenobiotic degradation. Our findings revealed stroke induces far-reaching and
robust changes to the intestinal mucosal microbiota. A better understanding of
the precise molecular events leading up to stroke-induced mucosal microbiota
changes may represent novel therapy targets to improve patient outcomes.
PMID- 29330444
TI - Lidocaine enhances the effects of chemotherapeutic drugs against bladder cancer.
AB - This study aimed to investigate whether lidocaine, alone or in combination with
other chemotherapeutic agents, inhibits the growth of human bladder cancer cells
in vitro and orthotopically transplanted bladder tumors in vivo. The effects of
lidocaine (1.25, 2.5 or 5 mg/mL), mitomycin C (MMC, 0.66 mg/mL), pirarubicin
(0.75 mg/mL) and Su Fu'ning lotion (SFN, 0.0625 mg/mL) on the proliferation of
human bladder cancer (BIU-87) cells were studied using the MTT assay. A Balb/c
nude mouse model of bladder cancer was developed by orthotopic transplantation of
BIU-87 cells, and the effects of intravesical instillation of lidocaine and MMC
on bladder wet weight (a measure of tumor size) and survival (over 60 days) were
studied. Lidocaine inhibited proliferation of BIU-87 cells in a concentration
dependent manner and (when given in combination) enhanced the actions of each of
the other antiproliferative agents. In tumor-bearing mice, MMC alone had no
effect on mean survival or bladder wet weight. However, the combination of 0.66
mg/mL MMC and 5 mg/mL lidocaine prolonged survival (from 34.62 +/- 6.49 to 49.30
+/- 6.72 days; n = 8, P < 0.05) and reduced bladder wet weight (from 68.94 +/-
53.61 to 20.26 +/- 6.07; n = 8, P < 0.05). Intravesical instillation of lidocaine
combined with other chemotherapeutic agents potentially could be an effective
therapy for bladder cancer.
PMID- 29330445
TI - A novel approach for correction of crosstalk effects in pathway analysis and its
application in osteoporosis research.
AB - Osteoporosis is a prevalent bone metabolic disease and peripheral blood monocytes
represent a major systemic cell type for bone metabolism. To identify the key
dysfunctional pathways in osteoporosis, we performed pathway analyses on
microarray data of monocytes from subjects with extremely high/low hip bone
mineral density. We first performed a traditional pathway analysis for which
different pathways were treated as independent. However, genes overlap among
pathways will lead to "crosstalk" phenomenon, which may lead to false
positive/negative results. Therefore, we applied correction techniques including
a novel approach that considers the correlation among genes to adjust the
crosstalk effects in the analysis. In traditional analysis, 10 pathways were
found to be significantly associated with BMD variation. After correction for
crosstalk effects, three of them remained significant. Moreover, the MAPK
signaling pathway, which has been shown to be important for osteoclastogenesis,
became significant only after the correction for crosstalk effects. We also
identified a new module mainly consisting of genes present in mitochondria to be
significant. In summary, we describe a novel method to correct the crosstalk
effect in pathway analysis and found five key independent pathways involved in
BMD regulation, which may provide a better understanding of biological functional
networks in osteoporosis.
PMID- 29330446
TI - Effect of puerarin in promoting fatty acid oxidation by increasing mitochondrial
oxidative capacity and biogenesis in skeletal muscle in diabetic rats.
AB - BACKGROUND: Type 2 diabetes is characterized by dyslipidemia and the accumulation
of lipids in non-adipose tissue, including skeletal muscle. Puerarin, which is a
natural isoflavonoid isolated from the root of the plant Pueraria lobata, has
been shown to have antidiabetic activity. However, the lipid-reducing effect of
puerarin, in particular in skeletal muscle, has not yet been addressed. METHODS:
We examined the effect of puerarin on mitochondrial function and the oxidation of
fatty acids in the skeletal muscle of high-fat diet/streptozotocin-induced
diabetic rats. RESULTS: Puerarin effectively alleviated dyslipidemia and
decreased the accumulation of intramyocellular lipids by upregulating the
expression of a range of genes involved in mitochondrial biogenesis, oxidative
phosphorylation, the detoxification of reactive oxygen species, and the oxidation
of fatty acids in the muscle of diabetic rats. Also, the effect of puerarin on
mitochondrial biogenesis might partially involve the function of the MU-opioid
receptor. In addition, puerarin decreased the trafficking of fatty acid
translocase/CD36 to the plasma membrane to reduce the uptake of fatty acids by
myocytes. In vitro studies confirmed that puerarin acted directly on muscle cells
to promote the oxidation of fatty acids in insulin-resistant myotubes treated
with palmitate. CONCLUSIONS: Puerarin improved the performance of mitochondria in
muscle and promoted the oxidation of fatty acids, which thus prevented the
accumulation of intramyocellular lipids in diabetic rats. Our findings will be
beneficial both for elucidating the mechanism of the antidiabetic activity of
puerarin and for promoting the therapeutic potential of puerarin in the treatment
of diabetes.
PMID- 29330447
TI - Human Placental-Derived Adherent Stromal Cells Co-Induced with TNF-alpha and IFN
gamma Inhibit Triple-Negative Breast Cancer in Nude Mouse Xenograft Models.
AB - Culturing 3D-expanded human placental-derived adherent stromal cells (ASCs) in
the presence of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN
gamma) transiently upregulated the secretion of numerous anti-proliferative, anti
angiogenic and pro-inflammatory cytokines. In a 3D-spheroid screening assay,
conditioned medium from these induced-ASCs inhibited proliferation of cancer cell
lines, including triple-negative breast cancer (TNBC) lines. In vitro co-culture
studies of induced-ASCs with MDA-MB-231 human breast carcinoma cells, a model
representing TNBC, supports a mechanism involving immunomodulation and
angiogenesis inhibition. In vivo studies in nude mice showed that intramuscular
administration of induced-ASCs halted MDA-MB-231 cell proliferation, and
inhibited tumor progression and vascularization. Thirty percent of treated mice
experienced complete tumor remission. Murine serum concentrations of the tumor
supporting cytokines Interleukin-6 (IL-6), Vascular endothelial growth factor
(VEGF) and Granulocyte-colony stimulating factor (G-CSF) were lowered to naive
levels. A somatic mutation analysis identified numerous genes which could be
screened in patients to increase a positive therapeutic outcome. Taken together,
these results show that targeted changes in the secretion profile of ASCs may
improve their therapeutic potential.
PMID- 29330449
TI - Lithium chloride effectively kills the honey bee parasite Varroa destructor by a
systemic mode of action.
AB - Honey bees are increasingly important in the pollination of crops and wild
plants. Recent reports of the weakening and periodical high losses of managed
honey bee colonies have alarmed beekeeper, farmers and scientists. Infestations
with the ectoparasitic mite Varroa destructor in combination with its associated
viruses have been identified as a crucial driver of these health problems.
Although yearly treatments are required to prevent collapses of honey bee
colonies, the number of effective acaricides is small and no new active compounds
have been registered in the past 25 years. RNAi-based methods were proposed
recently as a promising new tool. However, the application of these methods
according to published protocols has led to a surprising discovery. Here, we show
that the lithium chloride that was used to precipitate RNA and other lithium
compounds is highly effective at killing Varroa mites when fed to host bees at
low millimolar concentrations. Experiments with caged bees and brood-free
artificial swarms consisting of a queen and several thousand bees clearly
demonstrate the potential of lithium as miticidal agent with good tolerability in
worker bees providing a promising basis for the development of an effective and
easy-to-apply control method for mite treatment.
PMID- 29330452
TI - Assessment of the responses of soil pore properties to combined soil structure
amendments using X-ray computed tomography.
AB - Soil amendments, such as straw mulch, organic fertilizers and superabsorbent
polymer (SAP), are extensively applied to improve soil structure and porosity,
and we reported the functional consequences of the individual application of
these amendments in our previous study. However, whether combined amendments are
more effective than their individual applications for improving soil pore
structure is unknown. Here, we conducted X-ray computed tomography (CT) scanning
on undisturbed soil columns to investigate the efficiency of two-amendment
application, including straw mulch and organic manure, SAP and organic manure, or
SAP and straw mulch, for improving soil pore properties and pore distribution.
The X-ray CT technique allows us to accurately determine the number, morphology,
and location of macropores (>1 mm in diameter) and smaller pores (0.13-1.0 mm).
Compared to the control treatment, which showed the lowest increase in soil
porosity, all the combined treatments led to an increase in the numbers of both
macropores and smaller soil pores, causing a significant improvement in soil
structure and porosity. Among these treatments, the application of both straw
mulch and organic manure was the most effective for improving soil porosity and
soil physical structure.
PMID- 29330450
TI - C-terminal short arginine/serine repeat sequence-dependent regulation of Y14
(RBM8A) localization.
AB - Y14 (RBM8A) is an RNA recognition motif-containing protein that forms
heterodimers with MAGOH and serves as a core factor of the RNA surveillance
machinery for the exon junction complex (EJC). The role of the Y14 C-terminal
serine/arginine (RS) repeat-containing region, which has been reported to undergo
modifications such as phosphorylation and methylation, has not been sufficiently
investigated. Thus, we aimed to explore the functional significance of the Y14 C
terminal region. Deletion or dephosphorylation mimic mutants of the C-terminal
region showed a shift in localization from the nucleoplasmic region; in addition,
the C-terminal RS repeat-containing sequence itself exhibited the potential for
nucleolar localization. Additionally, the regulation of Y14 localization by the C
terminal region was further found to be exquisitely controlled by MAGOH binding.
Cumulatively, our findings, which demonstrated that Y14 localization is regulated
not only by the previously reported N-terminal localization signal but also by
the C-terminal RS repeat-containing region through phosphorylation and MAGOH
binding to Y14, provide new insights for the mechanism of localization of short
RS repeat-containing proteins.
PMID- 29330448
TI - Visual field loss and vision-related quality of life in the Italian Primary Open
Angle Glaucoma Study.
AB - The aim of this study was to examine the relationship between visual field (VF)
loss, vision-related quality of life (QoL) and glaucoma-related symptoms in a
large cohort of primary open angle glaucoma (POAG) patients. POAG patients with
or without VF defects or "glaucoma suspect" patients were considered eligible.
QoL was assessed using the validated versions of the 25-item National Eye
Institute Visual Function Questionnaire (NEI-VFQ-25) and glaucoma-related
symptoms were assessed using the Glaucoma Symptom Scale (GSS). Patients were
classified as having VF damage in one eye (VFD-1), both eyes (VFD-2), or neither
eye (VFD-0). 3227 patients were enrolled and 2940 were eligible for the analysis.
13.4% of patients were classified in the VFD-0, 23.7% in the VFD-1, and 62.9% in
the VFD-2 group. GSS visual symptoms domain (Func-4) and GSS non-visual symptoms
domain (Symp-6) scores were similar for the VFD-0 and VFD-1 groups (p = 0.133 and
p = 0.834 for Func-4 and Symp-6, respectively). VFD-0 group had higher scores
than VFD-2 both in Func-4 (p < 0.001) and Symp-6 domains (p = 0.035). Regarding
the NEI-VFQ-25, our data demonstrated that bilateral VF defects are associated
with vision-related QoL deterioration, irrespective of visual acuity.
PMID- 29330451
TI - Tracheophyte genomes keep track of the deep evolution of the Caulimoviridae.
AB - Endogenous viral elements (EVEs) are viral sequences that are integrated in the
nuclear genomes of their hosts and are signatures of viral infections that may
have occurred millions of years ago. The study of EVEs, coined paleovirology,
provides important insights into virus evolution. The Caulimoviridae is the most
common group of EVEs in plants, although their presence has often been overlooked
in plant genome studies. We have refined methods for the identification of
caulimovirid EVEs and interrogated the genomes of a broad diversity of plant
taxa, from algae to advanced flowering plants. Evidence is provided that almost
every vascular plant (tracheophyte), including the most primitive taxa
(clubmosses, ferns and gymnosperms) contains caulimovirid EVEs, many of which
represent previously unrecognized evolutionary branches. In angiosperms, EVEs
from at least one and as many as five different caulimovirid genera were
frequently detected, and florendoviruses were the most widely distributed,
followed by petuviruses. From the analysis of the distribution of different
caulimovirid genera within different plant species, we propose a working
evolutionary scenario in which this family of viruses emerged at latest during
Devonian era (approx. 320 million years ago) followed by vertical transmission
and by several cross-division host swaps.
PMID- 29330453
TI - Calcium sulfate induced versus PMMA-induced membrane in a critical-sized femoral
defect in a rat model.
AB - Aimed to investigate the characteristics of CS-induced membrane in comparison
with the PMMA-induced membrane. Cellular components, histological changes, growth
factor expressions of IL-6, VEGF, BMP-2, and TGF-beta1 in the two induced
membranes were compared at 2, 4, 6 and 8 weeks, respectively. We also compared
the histological changes at the bone defects between CS and PMMA groups. The
structural characteristics of induced membrane were similar between CS and PMMA.
Endochondral ossification took place in the CS-induced membrane at 8 week. Levels
of VEGF, BMP-2 and TGF-beta1 in CS-induced membrane were insignificantly higher
than those in PMMA-induced membrane at different time points. The expression of
IL-6 was significantly higher in PMMA-induced membranes at 2nd week. In addition,
osteogenic and neovascular activities of induced membranes increased with time
and peaked at 6 weeks. CS promoted endochondral ossification at the broken ends
of the bone defect than PMMA did. CS-induced membrane has a better capacity of
generating VEGF, BMP-2 and TGF-beta1.osteogenic and neovascular activities
achieve highest level at 6 week. CS may have the potential to replace PMMA as a
novel spacer in Masquelet technique.
PMID- 29330454
TI - Dynamic malaria hotspots in an open cohort in western Kenya.
AB - Malaria hotspots, defined as areas where transmission intensity exceeds the
average level, become more pronounced as transmission declines. Targeting
hotspots may accelerate reductions in transmission and could be pivotal for
malaria elimination. Determinants of hotspot location, particularly of their
movement, are poorly understood. We used spatial statistical methods to identify
foci of incidence of self-reported malaria in a large census population of 64,000
people, in 8,290 compounds over a 2.5-year study period. Regression models
examine stability of hotspots and identify static and dynamic correlates with
their location. Hotspot location changed over short time-periods, rarely
recurring in the same area. Hotspots identified in spring versus fall season
differed in their stability. Households located in a hotspot in the fall were
more likely to be located in a hotspot the following fall (RR = 1.77, 95% CI:
1.66-1.89), but the opposite was true for compounds in spring hotspots (RR =
0.15, 95% CI: 0.08-0.28). Location within a hotspot was related to environmental
and static household characteristics such as distance to roads or rivers. Human
migration into a household was correlated with risk of hotspot membership, but
the direction of the association differed based on the origin of the migration
event.
PMID- 29330455
TI - Towards Electrotuneable Nanoplasmonic Fabry-Perot Interferometer.
AB - Directed voltage-controlled assembly and disassembly of plasmonic nanoparticles
(NPs) at electrified solid-electrolyte interfaces (SEI) offer novel opportunities
for the creation of tuneable optical devices. We apply this concept to propose a
fast electrotuneable, NP-based Fabry-Perot (FP) interferometer, comprising two
parallel transparent electrodes in aqueous electrolyte, which form the
polarizable SEI for directed assembly-disassembly of negatively charged NPs. An
FP cavity between two reflective NP-monolayers assembled at such interfaces can
be formed or deconstructed under positive or negative polarization of the
electrodes, respectively. The inter-NP spacing may be tuned via applied
potential. Since the intensity, wavelength, and linewidth of the reflectivity
peak depend on the NP packing density, the transmission spectrum of the system
can thus be varied. A detailed theoretical model of the system's optical response
is presented, which shows excellent agreement with full-wave simulations. The
tuning of the peak transmission wavelength and linewidth is investigated in
detail. Design guidelines for such NP-based FP systems are established, where
transmission characteristics can be electrotuned in-situ, without mechanically
altering the cavity length.
PMID- 29330456
TI - 20-HETE promotes glucose-stimulated insulin secretion in an autocrine manner
through FFAR1.
AB - The long-chain fatty acid receptor FFAR1 is highly expressed in pancreatic beta
cells. Synthetic FFAR1 agonists can be used as antidiabetic drugs to promote
glucose-stimulated insulin secretion (GSIS). However, the physiological role of
FFAR1 in beta-cells remains poorly understood. Here we show that 20-HETE
activates FFAR1 and promotes GSIS via FFAR1 with higher potency and efficacy than
dietary fatty acids such as palmitic, linoleic, and alpha-linolenic acid. Murine
and human beta-cells produce 20-HETE, and the omega-hydroxylase-mediated
formation and release of 20-HETE is strongly stimulated by glucose.
Pharmacological inhibition of 20-HETE formation and blockade of FFAR1 in islets
inhibits GSIS. In islets from type-2 diabetic humans and mice, glucose-stimulated
20-HETE formation and 20-HETE-dependent stimulation of GSIS are strongly reduced.
We show that 20-HETE is an FFAR1 agonist, which functions as an autocrine
positive feed-forward regulator of GSIS, and that a reduced glucose-induced 20
HETE formation contributes to inefficient GSIS in type-2 diabetes.
PMID- 29330457
TI - Spatially selective responses to Kanizsa and occlusion stimuli in human visual
cortex.
AB - Early visual cortex responds to illusory contours in which abutting lines or
collinear edges imply the presence of an occluding surface, as well as to
occluded parts of an object. Here we used functional magnetic resonance imaging
(fMRI) and population receptive field (pRF) analysis to map retinotopic responses
in early visual cortex using bar stimuli defined by illusory contours, occluded
parts of a bar, or subtle luminance contrast. All conditions produced retinotopic
responses in early visual field maps even though signal-to-noise ratios were very
low. We found that signal-to-noise ratios and coherence with independent high
contrast mapping data increased from V1 to V2 to V3. Moreover, we found no
differences of signal-to-noise ratios or pRF sizes between the low-contrast
luminance and illusion conditions. We propose that all three conditions mapped
spatial attention to the bar location rather than activations specifically
related to illusory contours or occlusion.
PMID- 29330458
TI - Architecture of a mammalian glomerular domain revealed by novel volume
electroporation using nanoengineered microelectrodes.
AB - Dense microcircuit reconstruction techniques have begun to provide ultrafine
insight into the architecture of small-scale networks. However, identifying the
totality of cells belonging to such neuronal modules, the "inputs" and "outputs,"
remains a major challenge. Here, we present the development of nanoengineered
electroporation microelectrodes (NEMs) for comprehensive manipulation of a
substantial volume of neuronal tissue. Combining finite element modeling and
focused ion beam milling, NEMs permit substantially higher stimulation
intensities compared to conventional glass capillaries, allowing for larger
volumes configurable to the geometry of the target circuit. We apply NEMs to
achieve near-complete labeling of the neuronal network associated with a
genetically identified olfactory glomerulus. This allows us to detect sparse
higher-order features of the wiring architecture that are inaccessible to
statistical labeling approaches. Thus, NEM labeling provides crucial
complementary information to dense circuit reconstruction techniques. Relying
solely on targeting an electrode to the region of interest and passive
biophysical properties largely common across cell types, this can easily be
employed anywhere in the CNS.
PMID- 29330459
TI - A Novel Ultra-Stable, Monomeric Green Fluorescent Protein For Direct Volumetric
Imaging of Whole Organs Using CLARITY.
AB - Recent advances in thick tissue clearing are enabling high resolution, volumetric
fluorescence imaging of complex cellular networks. Fluorescent proteins (FPs)
such as GFP, however, can be inactivated by the denaturing chemicals used to
remove lipids in some tissue clearing methods. Here, we solved the crystal
structure of a recently engineered ultra-stable GFP (usGFP) and propose that the
two stabilising mutations, Q69L and N164Y, act to improve hydrophobic packing in
the core of the protein and facilitate hydrogen bonding networks at the surface,
respectively. usGFP was found to dimerise strongly, which is not desirable for
some applications. A point mutation at the dimer interface, F223D, generated
monomeric usGFP (muGFP). Neurons in whole mouse brains were virally transduced
with either EGFP or muGFP and subjected to Clear Lipid-exchanged Acrylamide
hybridized Rigid Imaging/Immunostaining/In situ hybridization-compatible Tissue
hYdrogel (CLARITY) clearing. muGFP fluorescence was retained after CLARITY
whereas EGFP fluorescence was highly attenuated, thus demonstrating muGFP is a
novel FP suitable for applications where high fluorescence stability and minimal
self-association are required.
PMID- 29330461
TI - Comparing olive oil and C4-dietary oil, a prodrug for the GPR119 agonist, 2
oleoyl glycerol, less energy intake of the latter is needed to stimulate incretin
hormone secretion in overweight subjects with type 2 diabetes.
AB - BACKGROUND/OBJECTIVE: After digestion, dietary triacylglycerol stimulates
incretin release in humans, mainly through generation of 2-monoacylglycerol, an
agonist for the intestinal G protein-coupled receptor 119 (GPR119). Enhanced
incretin release may have beneficial metabolic effects. However, dietary fat may
promote weight gain and should therefore be restricted in obesity. We designed C4
dietary oil (1,3-di-butyryl-2-oleoyl glycerol) as a 2-oleoyl glycerol (2-OG)
generating fat type, which would stimulate incretin release to the same extent
while providing less calories than equimolar amounts of common triglycerides,
e.g., olive oil. SUBJECTS AND METHODS: We studied the effect over 180 min of (a)
19 g olive oil plus 200 g carrot, (b) 10.7 g C4 dietary oil plus 200 g carrot and
(c) 200 g carrot, respectively, on plasma responses of gut and pancreatic
hormones in 13 overweight patients with type 2 diabetes (T2D). Theoretically,
both oil meals result in formation of 7.7 g 2-OG during digestion. RESULTS: Both
olive oil and C4-dietary oil resulted in greater postprandial (P <= 0.01)
glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide
(GIP) responses (incremental area under curve (iAUC)): iAUCGLP-1: 645 +/- 194 and
702 +/- 97 pM * min; iAUCGIP: 4,338 +/- 764 and 2,894 +/- 601 pM * min) compared
to the carrot meal (iAUCGLP-1: 7 +/- 103 pM * min; iAUCGIP: 266 +/- 234 pM *
min). iAUC for GLP-1 and GIP were similar for C4-dietary oil and olive oil,
although olive oil resulted in a higher peak value for GIP than C4-dietary oil.
CONCLUSION: C4-dietary oil enhanced secretion of GLP-1 and GIP to almost the same
extent as olive oil, in spite of liberation of both 2-OG and oleic acid, which
also may stimulate incretin secretion, from olive oil. Thus, C4-dietary oil is
more effective as incretin releaser than olive oil per unit of energy and may be
useful for dietary intervention.
PMID- 29330460
TI - Enhanced skeletal muscle ribosome biogenesis, yet attenuated mTORC1 and ribosome
biogenesis-related signalling, following short-term concurrent versus single-mode
resistance training.
AB - Combining endurance training with resistance training (RT) may attenuate skeletal
muscle hypertrophic adaptation versus RT alone; however, the underlying
mechanisms are unclear. We investigated changes in markers of ribosome
biogenesis, a process linked with skeletal muscle hypertrophy, following
concurrent training versus RT alone. Twenty-three males underwent eight weeks of
RT, either performed alone (RT group, n = 8), or combined with either high
intensity interval training (HIT+RT group, n = 8), or moderate-intensity
continuous training (MICT+RT group, n = 7). Muscle samples (vastus lateralis)
were obtained before training, and immediately before, 1 h and 3 h after the
final training session. Training-induced changes in basal expression of the 45S
ribosomal RNA (rRNA) precursor (45S pre-rRNA), and 5.8S and 28S mature rRNAs,
were greater with concurrent training versus RT. However, during the final
training session, RT further increased both mTORC1 (p70S6K1 and rps6
phosphorylation) and 45S pre-rRNA transcription-related signalling (TIF-1A and
UBF phosphorylation) versus concurrent training. These data suggest that when
performed in a training-accustomed state, RT induces further increases mTORC1 and
ribosome biogenesis-related signalling in human skeletal muscle versus concurrent
training; however, changes in ribosome biogenesis markers were more favourable
following a period of short-term concurrent training versus RT performed alone.
PMID- 29330462
TI - miR-143-3p inhibits the proliferation, migration and invasion in osteosarcoma by
targeting FOSL2.
AB - Osteosarcoma (OS) is the most common type of primary malignant bone tumor and
mainly occurs in children and adolescent. Because of its early migration and
invasion, OS has a poor prognosis. It has been reported that mircoRNAs (miRNAs)
play a crucial role in the occurrence and development of multiple tumors. In this
study, we identified the aberrant-expression of miR-143-3p in osteosarcoma and
examined the role of miR-143-3p in OS development. Further, we searched the miR
143-3p target gene and verified its accuracy by luciferase experiments. Finally,
we explored the relationship between miR-143-3p and FOS-Like antigen 2 (FOSL2).
Our data indicated that miR-143-3p expression was substantially lower in OS
tissues and cell-line compared with normal tissues, and was lower in patients
with poor prognosis. In addition miR-143-3p inhibited OS cell proliferation and
metastasis while promoting apoptosis. We next showed that FOSL2 was directly
targeted by miR-143-3p and could reverse the inhibition caused by miR-143-3p.
Finally, we found FOSL2 expression in OS cells was significantly higher compared
with normal cells and negatively correlated with miR-143-3p. Thus, miR-143-3p
directly and negatively targets FOSL2 to affect OS characteristics. This provides
a new target for the treatment of OS and deserves further study.
PMID- 29330463
TI - Effective photo-enhancement of cellular activity of fluorophore-octaarginine
antisense PNA conjugates correlates with singlet oxygen formation, endosomal
escape and chromophore lipophilicity.
AB - Photochemical internalization (PCI) is a cellular drug delivery method based on
the generation of light-induced reactive oxygen species (ROS) causing damage to
the endosomal membrane and thereby resulting in drug release to the cytoplasm. In
our study a series of antisense fluorophore octaarginine peptide nucleic acid
(PNA) conjugates were investigated in terms of PCI assisted cellular activity. It
is found that tetramethylrhodamine and Alexa Fluor 555 conjugated octaarginine
PNA upon irradiation exhibit more than ten-fold increase in antisense activity in
the HeLa pLuc705 luciferase splice correction assay. An analogous fluorescein
conjugate did not show any significant enhancement due to photobleaching, and
neither did an Alexa Fluor 488 conjugate. Using fluorescence microscopy a
correlation between endosomal escape and antisense activity was demonstrated, and
in parallel a correlation to localized formation of ROS assigned primarily to
singlet oxygen was also observed. The results show that tetramethylrhodamine (and
to lesser extent Alexa Fluor 555) conjugated octaarginine PNAs are as effectively
delivered to the cytosol compartment by PCI as by chloroquine assisted delivery
and also indicate that efficient photodynamic endosomal escape is strongly
dependent on the quantum yield for photochemical singlet oxygen formation,
photostability as well as the lipophilicity of the chromophore.
PMID- 29330465
TI - Insulin Resistance is Associated with Cognitive Decline Among Older Koreans with
Normal Baseline Cognitive Function: A Prospective Community-Based Cohort Study.
AB - We evaluated whether metabolic factors were associated with cognitive decline,
compared to baseline cognitive function, among geriatric population. The present
study evaluated data from an ongoing prospective community-based Korean cohort
study. Among 1,387 participants who were >65 years old, 422 participants were
evaluated using the Korean mini-mental status examination (K-MMSE) at the
baseline and follow-up examinations. The mean age at the baseline was 69.3 +/-
2.9 years, and 222 participants (52.6%) were men. The mean duration of education
was 7.1 +/- 3.6 years. During a mean follow-up of 5.9 +/- 0.1 years, the K-MMSE
score significantly decreased (-1.1 +/- 2.7 scores), although no significant
change was observed in the homeostasis model assessment of insulin resistance
(HOMA-IR) value. Participants with more decreased percent changes in K-MMSE
scores had a shorter duration of education (p = 0.001), older age (p = 0.022),
higher baseline K-MMSE score (p < 0.001), and increased insulin resistance (?HOMA
IR, p = 0.002). The correlation between the percent changes in K-MMSE and ?HOMA
IR values remained significant after multivariable adjustment (B = -0.201, p =
0.002). During a 6-year follow-up of older Koreans with normal baseline cognitive
function, increased insulin resistance was significantly correlated with
decreased cognitive function.
PMID- 29330464
TI - Eltrombopag versus romiplostim in treatment of children with persistent or
chronic immune thrombocytopenia: a systematic review incorporating an indirect
comparison meta-analysis.
AB - In absence of direct comparison, we conducted an indirect-comparison meta
analysis to evaluate the efficacy and safety of thrombopoietin-receptor
agonists(TPO-RAs) in treatment of pediatric persistent or chronic immune
thrombocytopenia(ITP). PubMed, Embase, Cochrane Library, Clinical Trials.gov,
China National Knowledge Infrastructure, and Chinese Biomedical Literature
Database were searched from their earliest records to May 2017. Randomized
controlled trials comparing the TPO-RAs with placebo in pediatric ITP were
included. Outcomes included overall response rate(primary), durable response,
overall or clinically significant bleeding, the proportion of patients receiving
rescue medication, and safety. Five randomized placebo-controlled studies(N =
261) were analyzed. The overall response[Risk Ratio(RR) 0.57, 95% confidence
interval(CI) 0.21-1.56], the incidence of adverse events (RR 0.96, 95%CI 0.66
1.39), durable response(RR 2.48, 95%CI 0.31-19.97), and the proportion of
patients receiving rescue treatment(RR 0.73, 95%CI 0.20-2.73) were similar
between eltrombopag and romiplostim group. Nevertheless, eltrombopag might have
lower risk of overall bleeding(RR 0.43, 95%CI 0.23-0.80) and clinically
significant bleeding(RR 0.33, 95%CI 0.12-0.89) than romiplostim. This meta
analysis suggests that eltrombopag might be similar to romiplostim in efficacy
and safety, but seems to reduce the risk of bleeding compared to romiplostim.
Furthermore, cost of the treatment, comorbidity of patients and drug compliance
should also be considered in clinical decision making.
PMID- 29330466
TI - Target engagement imaging of PARP inhibitors in small-cell lung cancer.
AB - Insufficient chemotherapy response and rapid disease progression remain concerns
for small-cell lung cancer (SCLC). Oncologists rely on serial CT scanning to
guide treatment decisions, but this cannot assess in vivo target engagement of
therapeutic agents. Biomarker assessments in biopsy material do not assess
contemporaneous target expression, intratumoral drug exposure, or drug-target
engagement. Here, we report the use of PARP1/2-targeted imaging to measure target
engagement of PARP inhibitors in vivo. Using a panel of clinical PARP inhibitors,
we show that PARP imaging can quantify target engagement of chemically diverse
small molecule inhibitors in vitro and in vivo. We measure PARP1/2 inhibition
over time to calculate effective doses for individual drugs. Using patient
derived xenografts, we demonstrate that different therapeutics achieve similar
integrated inhibition efficiencies under different dosing regimens. This imaging
approach to non-invasive, quantitative assessment of dynamic intratumoral target
inhibition may improve patient care through real-time monitoring of drug
delivery.
PMID- 29330467
TI - Evidence for sparse synergies in grasping actions.
AB - Converging evidence shows that hand-actions are controlled at the level of
synergies and not single muscles. One intriguing aspect of synergy-based action
representation is that it may be intrinsically sparse and the same synergies can
be shared across several distinct types of hand-actions. Here, adopting a
normative angle, we consider three hypotheses for hand-action optimal-control:
sparse-combination hypothesis (SC) - sparsity in the mapping between synergies
and actions - i.e., actions implemented using a sparse combination of synergies;
sparse-elements hypothesis (SE) - sparsity in synergy representation - i.e., the
mapping between degrees-of-freedom (DoF) and synergies is sparse; double-sparsity
hypothesis (DS) - a novel view combining both SC and SE - i.e., both the mapping
between DoF and synergies and between synergies and actions are sparse, each
action implementing a sparse combination of synergies (as in SC), each using a
limited set of DoFs (as in SE). We evaluate these hypotheses using hand kinematic
data from six human subjects performing nine different types of reach-to-grasp
actions. Our results support DS, suggesting that the best action representation
is based on a relatively large set of synergies, each involving a reduced number
of degrees-of-freedom, and that distinct sets of synergies may be involved in
distinct tasks.
PMID- 29330468
TI - Alteration in yield and oil quality traits of winter rapeseed by lodging at
different planting density and nitrogen rates.
AB - Lodging is a factor that negatively affects yield, seed quality, and harvest
ability in winter rapeseed (Brassica napus L.). In this study, we quantified the
lodging-induced yield losses, changes in fatty acid composition, and oil quality
in rapeseed under different nitrogen application rates and planting densities.
Field experiments were conducted in 2014-2017 for studying the effect of manually
induced lodging angles (0 degrees , 30 degrees , 60 degrees , and 90 degrees ),
10, 20 and 30 d post-flowering at different densities and nitrogen application
rates. The fertilization/planting density combination N270D45 produced the
maximum observed yield and seed quality. Timing and angle of lodging had
significant effects on yield. Lodging at 90 degrees induced at 10 d post
flowering caused the maximum reduction in yield, biomass, and silique
photosynthesis. Seed yield losses were higher at high N application rates, the
maximum being at N360D45. Lodging decreased seed oil content and altered its
fatty acid composition by increasing stearic and palmitic acid content, while
decreasing linoleic and linolenic acid content, and deteriorating oil quality by
increasing erucic acid and glucosinolate content. Therefore, lodging-induced
yield loss and reduction in oil content might be reduced by selecting optimum N
level and planting density.
PMID- 29330470
TI - beta-Ecdysterone protects SH-SY5Y cells against beta-amyloid-induced apoptosis
via c-Jun N-terminal kinase- and Akt-associated complementary pathways.
AB - Recently, the significantly higher incidence of Alzheimer's disease (AD) in women
than in men has been attributed to the loss of neuroprotective estrogen after
menopause. Does phytoestrogen have the ability to protect against amyloid-beta
(Abeta) toxicity? The aim of this study was to evaluate hypothesis that beta
ecdysterone (beta-Ecd) protects SH-SY5Y cells from Abeta-induced apoptosis by
separate signaling pathways involving protein kinase B (Akt) and c-Jun N-terminal
kinase (JNK). Here, we demonstrate that phytoestrogen beta-Ecd inhibits Abeta
triggered mitochondrial apoptotic pathway, as indicated by Bcl-2/Bax ratio
elevation, cytochrome c (cyt c) release reduction, and caspase-9 inactivation.
Interestingly, beta-Ecd upregulates Bcl-2 expression in SH-SY5Y cells under both
basal and Abeta-challenged conditions, but downregulates Bax expression only in
Abeta-challenged conditions. Subsequently, Akt-dependent NF-kappaB activation is
required for Bcl-2 upregulation, but not Bax downregulation, in response to beta
Ecd, which was validated by the use of LY294002 and Bay11-7082. Notably, beta-Ecd
attenuates the Abeta-evoked reactive oxygen species (ROS) production, apoptosis
signal-regulating kinase 1 (ASK1) phosphorylation and JNK activation without
altering the basal ASK1 phosphorylation and JNK activation. ROS-scavenging by
diphenyleneiodonium (DPI) abrogated the ability of beta-Ecd to alter the
activation of ASK1. Simultaneously, inhibition of JNK by SP600125 abolished beta
Ecd-induced Bax downregulation in Abeta-challenged SH-SY5Y cells, whereas
LY294002 failed to do so. Consequently, beta-Ecd possesses neuroprotection by
different and complementary pathways, which together promote a Bcl-2/Bax ratio.
These data support our hypothesis and suggest that beta-Ecd is a promising
candidate for the treatment of AD.
PMID- 29330469
TI - Mycobacterium tuberculosis Exploits a Molecular Off Switch of the Immune System
for Intracellular Survival.
AB - Mycobacterium tuberculosis (M. tuberculosis) survives and multiplies inside human
macrophages by subversion of immune mechanisms. Although these immune evasion
strategies are well characterised functionally, the underlying molecular
mechanisms are poorly understood. Here we show that during infection of human
whole blood with M. tuberculosis, host gene transcriptional suppression, rather
than activation, is the predominant response. Spatial, temporal and functional
characterisation of repressed genes revealed their involvement in pathogen
sensing and phagocytosis, degradation within the phagolysosome and antigen
processing and presentation. To identify mechanisms underlying suppression of
multiple immune genes we undertook epigenetic analyses. We identified
significantly differentially expressed microRNAs with known targets in suppressed
genes. In addition, after searching regions upstream of the start of
transcription of suppressed genes for common sequence motifs, we discovered novel
enriched composite sequence patterns, which corresponded to Alu repeat elements,
transposable elements known to have wide ranging influences on gene expression.
Our findings suggest that to survive within infected cells, mycobacteria exploit
a complex immune "molecular off switch" controlled by both microRNAs and Alu
regulatory elements.
PMID- 29330471
TI - SLC26A3 (DRA) prevents TNF-alpha-induced barrier dysfunction and dextran sulfate
sodium-induced acute colitis.
AB - SLC26A3 encodes a Cl-/HCO3- ion transporter that is also known as downregulated
in adenoma (DRA) and is involved in HCO3-/mucus formation. The role of DRA in the
epithelial barrier has not been previously established. In this study, we
investigated the in vivo and in vitro mechanisms of DRA in the colon epithelial
barrier. Immunofluorescence (IF) and co-immunoprecipitation (co-IP) studies
reveal that DRA binds directly to tight junction (TJ) proteins and affects the
expression of TJ proteins in polarized Caco-2BBe cells. Similarly, DRA
colocalizes with ZO-1 in the intestinal epithelium. Knockdown or overexpression
of DRA leads to alterations in TJ proteins and epithelial permeability. In
addition, TNF-alpha treatment downregulates DRA by activating NF-kB and
subsequently affecting intestinal epithelial barrier integrity. Furthermore,
overexpression of DRA partly reverses the TNF-alpha-induced damage by stabilizing
TJ proteins. Neutralization of TNF-alpha in dextran sulfate sodium (DSS)-induced
colitis mice demonstrates improved the outcomes, and the therapeutic effect of
the TNF-alpha neutralizing mAb is mediated in part by the preservation of DRA
expression. These data suggest that DRA may be one of the therapeutic targets of
TNF-alpha. Moreover, DRA delivered by adenovirus vector significantly prevents
the exacerbation of colitis and improves epithelial barrier function by promoting
the recovery of TJ proteins in DSS-treated mice. In conclusion, DRA plays a role
in protecting the epithelial barrier and may be a therapeutic target in gut
homeostasis.
PMID- 29330472
TI - Amyloid deposition in a mouse model humanized at the transthyretin and retinol
binding protein 4 loci.
AB - Familial amyloidotic polyneuropathy is an autosomal dominant disorder caused by a
point mutation in the transthyretin (TTR) gene. The process of TTR
amyloidogenesis begins with rate-limiting dissociation of the TTR tetramer. Thus,
the TTR stabilizers, such as Tafamidis and Diflunisal, are now in clinical
trials. Mouse models will be useful to testing the efficacy of these drugs.
Although several mouse models have been generated, they all express mouse Rbp4.
Thus, human TTR associates with mouse RBP4, resulting in different kinetic and
thermodynamic stability profiles of TTR tetramers. To overcome this problem, we
previously produced humanized mouse strains at both the TTR and Rbp4 loci (Ttr
hTTRVal30 , Ttr hTTRMet30 , and Rbp4 hRBP4 ). By mating these mice, we produced
double-humanized mouse strains, Ttr hTTRVal30/hTTRVal30 :Rbp4 hRBP4/hRBP4 and Ttr
hTTRVal30/Met30 :Rbp4 hRBP4/hRBP4 . We used conventional transgenic mouse strains
on a wild-type (Ttr +/+ :Tg[6.0hTTRMet30]) or knockout Ttr background (Ttr-/
:Tg[6.0hTTRMet30]) as reference strains. The double-humanized mouse showed 1/25
of serum hTTR and 1/40 of serum hRBP4 levels. However, amyloid deposition was
more pronounced in Ttr hTTRVal30/Met30 :Rbp4 hRBP4/hRBP4 than in conventional
transgenic mouse strains. In addition, a similar amount of amyloid deposition was
also observed in Ttr hTTRVal30/ hTTRVal30 :Rbp4 hRBP4/ hRBP4 mice that carried
the wild-type human TTR gene. Furthermore, amyloid deposition was first observed
in the sciatic nerve without any additional genetic change. In all strains, anti
TTR antibody-positive deposits were found in earlier age and at higher percentage
than amyloid fibril deposition. In double-humanized mice, gel filtration analysis
of serum revealed that most hTTR was free of hRBP4, suggesting importance of free
TTR for amyloid deposition.
PMID- 29330473
TI - Endothelial heparan sulfate deficiency reduces inflammation and fibrosis in
murine diabetic nephropathy.
AB - Inflammation plays a vital role in the development of diabetic nephropathy, but
the underlying regulatory mechanisms are only partially understood. Our previous
studies demonstrated that, during acute inflammation, endothelial heparan sulfate
(HS) contributes to the adhesion and transendothelial migration of leukocytes
into perivascular tissues by direct interaction with L-selectin and the
presentation of bound chemokines. In the current study, we aimed to assess the
role of endothelial HS on chronic renal inflammation and fibrosis in a diabetic
nephropathy mouse model. To reduce sulfation of HS specifically in the
endothelium, we generated Ndst1 f/f Tie2Cre + mice in which N-deacetylase/N
sulfotransferase-1 (Ndst1), the gene that initiates HS sulfation modifications in
HS biosynthesis, was expressly ablated in endothelium. To induce diabetes, age
matched male Ndst1 f/f Tie2Cre - (wild type) and Ndst1 f/f Tie2Cre + mice on a
C57Bl/6J background were injected intraperitoneally with streptozotocin (STZ) (50
mg/kg) on five consecutive days (N = 10-11/group). Urine and plasma were
collected. Four weeks after diabetes induction the animals were sacrificed and
kidneys were analyzed by immunohistochemistry and qRT-PCR. Compared to healthy
controls, diabetic Ndst1 f/f Tie2Cre - mice showed increased glomerular
macrophage infiltration, mannose binding lectin complement deposition and
glomerulosclerosis, whereas these pathological reactions were prevented
significantly in the diabetic Ndst1 f/f Tie2Cre + animals (all three p < 0.01).
In addition, the expression of the podocyte damage marker desmin was
significantly higher in the Ndst1 f/f Tie2Cre - group compared to the Ndst1 f/f
Tie2Cre + animals (p < 0.001), although both groups had comparable numbers of
podocytes. In the cortical tubulo-interstitium, similar analyses show decreased
interstitial macrophage accumulation in the diabetic Ndst1 f/f Tie2Cre + animals
compared to the diabetic Ndst1 f/f Tie2Cre - mice (p < 0.05). Diabetic Ndst1 f/f
Tie2Cre + animals also showed reduced interstitial fibrosis as evidenced by
reduced density of alphaSMA-positive myofibroblasts (p < 0.01), diminished
collagen III deposition (p < 0.001) and reduced mRNA expression of collagen I (p
< 0.001) and fibronectin (p < 0.001). Our studies indicate a pivotal role of
endothelial HS in the development of renal inflammation and fibrosis in diabetic
nephropathy in mice. These results suggest that HS is a possible target for
therapy in diabetic nephropathy.
PMID- 29330475
TI - Recent enhanced high-summer North Atlantic Jet variability emerges from three
century context.
AB - A recent increase in mid-latitude extreme weather events has been linked to
Northern Hemisphere polar jet stream anomalies. To put recent trends in a
historical perspective, long-term records of jet stream variability are needed.
Here we combine two tree-ring records from the British Isles and the northeastern
Mediterranean to reconstruct variability in the latitudinal position of the high
summer North Atlantic Jet (NAJ) back to 1725 CE. We find that northward NAJ
anomalies have resulted in heatwaves and droughts in northwestern Europe and
southward anomalies have promoted wildfires in southeastern Europe. We further
find an unprecedented increase in NAJ variance since the 1960s, which co-occurs
with enhanced late twentieth century variance in the Central and North Pacific
Basin. Our results suggest increased late twentieth century interannual
meridional jet stream variability and support more sinuous jet stream patterns
and quasi-resonant amplification as potential dynamic pathways for Arctic warming
to influence mid-latitude weather.
PMID- 29330474
TI - A De Novo FOXP1 Truncating Mutation in a Patient Originally Diagnosed as C
Syndrome.
AB - De novo FOXP1 mutations have been associated with intellectual disability (ID),
motor delay, autistic features and a wide spectrum of speech difficulties. C
syndrome (Opitz C trigonocephaly syndrome) is a rare and genetically
heterogeneous condition, characterized by trigonocephaly, craniofacial anomalies
and ID. Several different chromosome deletions and and point mutations in
distinct genes have been associated with the disease in patients originally
diagnosed as Opitz C. By whole exome sequencing we identified a de novo splicing
mutation in FOXP1 in a patient, initially diagnosed as C syndrome, who suffers
from syndromic intellectual disability with trigonocephaly. The mutation (c.1428
+ 1 G > A) promotes the skipping of exon 16, a frameshift and a premature STOP
codon (p.Ala450GLyfs*13), as assessed by a minigene strategy. The patient
reported here shares speech difficulties, intellectual disability and autistic
features with other FOXP1 syndrome patients, and thus the diagnosis for this
patient should be changed. Finally, since trigonocephaly has not been previously
reported in FOXP1 syndrome, it remains to be proved whether it may be associated
with the FOXP1 mutation.
PMID- 29330476
TI - High-performance flexible supercapacitors based on electrochemically tailored
three-dimensional reduced graphene oxide networks.
AB - A simple approach for growing porous electrochemically reduced graphene oxide
(pErGO) networks on copper wire, modified with galvanostatically deposited copper
foam is demonstrated. The as-prepared pErGO networks on the copper wire are
directly used to fabricate solid-state supercapacitor. The pErGO-based
supercapacitor can deliver a specific capacitance (Csp) as high as 81+/-3 F g-1
at 0.5 A g-1 with polyvinyl alcohol/H3PO4 gel electrolyte. The Csp per unit
length and area are calculated as 40.5 mF cm-1 and 283.5 mF cm-2, respectively.
The shape of the voltammogram retained up to high scan rate of 100 V s-1. The
pErGO-based supercapacitor device exhibits noticeably high charge-discharge
cycling stability, with 94.5% Csp retained even after 5000 cycles at 5 A g-1.
Nominal change in the specific capacitance, as well as the shape of the
voltammogram, is observed at different bending angles of the device even after
5000 cycles. The highest energy density of 11.25 W h kg-1 and the highest power
density of 5 kW kg-1 are also achieved with this device. The wire-based
supercapacitor is scalable and highly flexible, which can be assembled
with/without a flexible substrate in different geometries and bending angles for
illustrating promising use in smart textile and wearable device.
PMID- 29330477
TI - Labile organic carbon pools and enzyme activities of Pinus massoniana plantation
soil as affected by understory vegetation removal and thinning.
AB - The effects of forest management on carbon (C) sequestration are poorly
understood, particularly in the Three Gorges Reservoir area. We aimed to identify
the effects of forest management on C sequestration in Pinus massoniana
plantations. An intact control forest (CK), a site undergoing regular shrub
cutting with the simultaneous removal of residues (SC), a site under low
intensity thinning (LIT), and a site under high-intensity thinning (HIT) were
compared for soil labile organic carbon (LOC), related enzyme activities, and
soil characteristics. Soil organic carbon (SOC) significantly decreased in the
HIT treatment as compared with that in the CK treatment. Soil EOC, DOC, MBC
contents in treated plots were higher than those in the CK treatment;
particularly, the HIT treatment significantly increased those values in 0-10 cm
layer. Thinning resulted in a decrease in cellulase and amylase activities, but
an increase in invertase activity. In addition, the SOC content was significantly
correlated with four enzymes activities and LOC components, which suggested that
the soil LOC components and enzymes activities were sensitive to the changes of
SOC. Our results suggest that high-intensity thinning treatment in Pinus
massoniana plantation could significantly decrease the SOC content and lead to an
increase of LOC components.
PMID- 29330479
TI - Titania (TiO2) nanoparticles enhance the performance of growth-promoting
rhizobacteria.
AB - A novel use of nanotitania (TNs) as agents in the nanointerface interaction
between plants and colonization of growth promoting rhizobacteria (PGPR) is
presented. The effectiveness of PGPRs is related to the effectiveness of the
technology used for their formulation. TNs produced by the Captigel patented
SolGel approach, characterized by the transmission and scanning electron
microscopy were used for formulation of the harsh environment PGPR strains.
Changes in the biomass of wheat seedlings and in the density of single and double
inoculants with and without TNs were monitored during two weeks of stress induced
by drought salt and by the pathogen Fusarium culmorum. We show that double
inoculants with TNs can attach stably to plant roots. Regression analysis
indicates that there is a positive interaction between seedling biomass and TN
treated second inoculant colonization. We conclude that TN treatment provides an
effectual platform for PGPR rational application via design of root microbial
community. Our studies illustrate the importance of considering natural soil
nanoparticles for PGPR application and thereby may explain the generally observed
inconsistent behavior of PGPRs in the field. These new advancements importantly
contribute towards solving food security issues in changing climates. The model
systems established here provide a basis for new PGPR nanomaterials research.
PMID- 29330478
TI - Interaction of suppressor of cytokine signalling 3 with cavin-1 links SOCS3
function and cavin-1 stability.
AB - Effective suppression of JAK-STAT signalling by the inducible inhibitor
"suppressor of cytokine signalling 3" (SOCS3) is essential for limiting
signalling from cytokine receptors. Here we show that cavin-1, a component of
caveolae, is a functionally significant SOCS3-interacting protein. Biochemical
and confocal imaging demonstrate that SOCS3 localisation to the plasma membrane
requires cavin-1. SOCS3 is also critical for cavin-1 stabilisation, such that
deletion of SOCS3 reduces the expression of cavin-1 and caveolin-1 proteins,
thereby reducing caveola abundance in endothelial cells. Moreover, the
interaction of cavin-1 and SOCS3 is essential for SOCS3 function, as loss of
cavin-1 enhances cytokine-stimulated STAT3 phosphorylation and abolishes SOCS3
dependent inhibition of IL-6 signalling by cyclic AMP. Together, these findings
reveal a new functionally important mechanism linking SOCS3-mediated inhibition
of cytokine signalling to localisation at the plasma membrane via interaction
with and stabilisation of cavin-1.
PMID- 29330480
TI - Anti-correlated cortical networks arise from spontaneous neuronal dynamics at
slow timescales.
AB - In the highly interconnected architectures of the cerebral cortex, recurrent
intracortical loops disproportionately outnumber thalamo-cortical inputs. These
networks are also capable of generating neuronal activity without feedforward
sensory drive. It is unknown, however, what spatiotemporal patterns may be solely
attributed to intrinsic connections of the local cortical network. Using high
density microelectrode arrays, here we show that in the isolated, primary
somatosensory cortex of mice, neuronal firing fluctuates on timescales from
milliseconds to tens of seconds. Slower firing fluctuations reveal two spatially
distinct neuronal ensembles, which correspond to superficial and deeper layers.
These ensembles are anti-correlated: when one fires more, the other fires less
and vice versa. This interplay is clearest at timescales of several seconds and
is therefore consistent with shifts between active sensing and anticipatory
behavioral states in mice.
PMID- 29330482
TI - Normal karyotype in myelofibrosis: is prognostic integrity affected by the number
of metaphases analyzed?
PMID- 29330481
TI - FDXR is a biomarker of radiation exposure in vivo.
AB - Previous investigations in gene expression changes in blood after radiation
exposure have highlighted its potential to provide biomarkers of exposure. Here,
FDXR transcriptional changes in blood were investigated in humans undergoing a
range of external radiation exposure procedures covering several orders of
magnitude (cardiac fluoroscopy, diagnostic computed tomography (CT)) and
treatments (total body and local radiotherapy). Moreover, a method was developed
to assess the dose to the blood using physical exposure parameters. FDXR
expression was significantly up-regulated 24 hr after radiotherapy in most
patients and continuously during the fractionated treatment. Significance was
reached even after diagnostic CT 2 hours post-exposure. We further showed that no
significant differences in expression were found between ex vivo and in vivo
samples from the same patients. Moreover, potential confounding factors such as
gender, infection status and anti-oxidants only affect moderately FDXR
transcription. Finally, we provided a first in vivo dose-response showing dose
dependency even for very low doses or partial body exposure showing good
correlation between physically and biologically assessed doses. In conclusion, we
report the remarkable responsiveness of FDXR to ionising radiation at the
transcriptional level which, when measured in the right time window, provides
accurate in vivo dose estimates.
PMID- 29330483
TI - Neural Correlates of Sexual Orientation in Heterosexual, Bisexual, and Homosexual
Women.
AB - We used fMRI to investigate neural correlates of responses to erotic pictures and
videos in heterosexual (N = 26), bisexual (N = 26), and homosexual (N = 24)
women, ages 25-50. We focused on the ventral striatum, an area of the brain
associated with desire, extending previous findings from the sexual
psychophysiology literature in which homosexual women had greater category
specificity (relative to heterosexual and bisexual women) in their responses to
male and female erotic stimuli. We found that homosexual women's subjective and
neural responses reflected greater bias towards female stimuli, compared with
bisexual and heterosexual women, whose responses did not significantly differ.
These patterns were also suggested by whole brain analyses, with homosexual women
showing category-specific activations of greater extents in visual and auditory
processing areas. Bisexual women tended to show more mixed patterns, with
activations more responsive to female stimuli in sensory processing areas, and
activations more responsive to male stimuli in areas associated with social
cognition.
PMID- 29330484
TI - Single-cell RNA-sequencing resolves self-antigen expression during mTEC
development.
AB - The crucial capability of T cells for discrimination between self and non-self
peptides is based on negative selection of developing thymocytes by medullary
thymic epithelial cells (mTECs). The mTECs purge autoreactive T cells by
expression of cell-type specific genes referred to as tissue-restricted antigens
(TRAs). Although the autoimmune regulator (AIRE) protein is known to promote the
expression of a subset of TRAs, its mechanism of action is still not fully
understood. The expression of TRAs that are not under the control of AIRE also
needs further characterization. Furthermore, expression patterns of TRA genes
have been suggested to change over the course of mTEC development. Herein we have
used single-cell RNA-sequencing to resolve patterns of TRA expression during mTEC
development. Our data indicated that mTEC development consists of three distinct
stages, correlating with previously described jTEC, mTEChi and mTEClo phenotypes.
For each subpopulation, we have identified marker genes useful in future studies.
Aire-induced TRAs were switched on during jTEC-mTEC transition and were expressed
in genomic clusters, while otherwise the subsets expressed largely overlapping
sets of TRAs. Moreover, population-level analysis of TRA expression frequencies
suggested that such differences might not be necessary to achieve efficient
thymocyte selection.
PMID- 29330485
TI - The Structure of Metal Binding Domain 1 of the Copper Transporter ATP7B Reveals
Mechanism of a Singular Wilson Disease Mutation.
AB - Copper-transporter ATP7B maintains copper homeostasis in the human cells and
delivers copper to the biosynthetic pathways for incorporation into the newly
synthesized copper-containing proteins. ATP7B is a target of several hundred
mutations that lead to Wilson disease, a chronic copper toxicosis. ATP7B contains
a chain of six cytosolic metal-binding domains (MBDs), the first four of which
(MBD1-4) are believed to be regulatory, and the last two (MBD5-6) are required
for enzyme activity. We report the NMR structure of MBD1, the last unsolved metal
binding domain of ATP7B. The structure reveals the disruptive mechanism of G85V
mutation, one of the very few disease causing missense mutations in the MBD1-4
region of ATP7B.
PMID- 29330486
TI - New generation of drug delivery systems based on ginsenoside Rh2-, Lysine- and
Arginine-treated highly porous graphene for improving anticancer activity.
AB - In this study, Rh2-treated graphene oxide (GO-Rh2), lysine-treated highly porous
graphene (Gr-Lys), arginine-treated Gr (Gr-Arg), Rh2-treated Gr-Lys (Gr-Lys-Rh2)
and Rh2-treated Gr-Arg (Gr-Arg-Rh2) were synthesized. MTT assay was used for
evaluation of cytotoxicity of samples on ovarian cancer (OVCAR3), breast cancer
(MDA-MB), Human melanoma (A375) and human mesenchymal stem cells (MSCs) cell
lines. The percentage of apoptotic cells was determined by terminal
deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. The
hemolysis and blood coagulation activity of nanostructures were performed.
Interestingly, Gr-Arg, Gr-Lys, Gr-Arg-Rh2, and Gr-Lys-Rh2 were more active
against cancer cell lines in comparison with their cytotoxic activity against
normal cell lines (MSCs) with IC50 values higher than 100 MUg/ml. The results of
TUNEL assay indicates a significant increase in the rates of TUNEL positive cells
by increasing the concentrations of nanomaterials. Results were also shown that
aggregation and changes of RBCs morphology were occurred in the presence of GO,
GO-Rh2, Gr-Arg, Gr-Lys, Gr-Arg-Rh2, and Gr-Lys-Rh2. Note that all the samples had
effect on blood coagulation system, especially on PTT. All nanostrucure act as
antitumor drug so that binding of drugs to a nostructures is irresolvable and the
whole structure enter to the cell as a drug.
PMID- 29330487
TI - A Biomarker Characterizing Neurodevelopment with applications in Autism.
AB - Despite great advances in neuroscience and genetic studies, our understanding of
neurodevelopmental disorders is still quite limited. An important reason is not
having objective psychiatric clinical tests. Here we propose a quantitative
neurodevelopment assessment by studying natural movement outputs. Movement is
central to behaviors: It involves complex coordination, temporal alterations, and
precise dynamic controls. We carefully analyzed the continuous movement output
data, collected with high definition electromagnetic sensors at millisecond time
scales. We unraveled new metrics containing striking physiological information
that was unseen neither by using traditional motion assessments nor by naked eye
observations. Our putative biomarker leads to precise individualized
classifications. It illustrates clear differences between Autism Spectrum
Disorder (ASD) subjects from mature typical developing (TD) individuals. It
provides an ASD complementary quantitative classification, which closely agrees
with the clinicaly assessed functioning levels in the spectrum. It also
illustrates TD potential age-related neurodevelopmental trajectories. Applying
our movement biomarker to the parents of the ASD individuals studied in the
cohort also shows a novel potential familial signature ASD tie. This paper
proposes a putative behavioral biomarker to characterize the level of
neurodevelopment with high predicting power, as illustrated in ASD subjects as an
example.
PMID- 29330488
TI - Motor skill learning and reward consumption differentially affect VTA activation.
AB - Dopamine release from the ventral tegmental area (VTA) terminals in the primary
motor cortex (M1) enables motor skill acquisition. Here, we test the hypothesis
that dopaminergic VTA neurons projecting to M1 are activated when rewards are
obtained during motor skill acquisition, but not during task execution at plateau
performance, or by rewards obtained without performing skilled movements. Rats
were trained to perform a skilled reaching task for 3 days (acquisition) or 7
days (plateau). In combination with retrograde labelling of VTA-to-M1 projection
neurons, double immunofluorescence for c-fos and tyrosine hydroxylase (TH) was
used to assess activation of dopaminergic and non-dopaminergic VTA neurons.
Dopaminergic VTA-to-M1 projection neurons were indeed activated during successful
motor skill acquisition, but not when rats failed to learn or had reached plateau
performance, nor by food rewards alone. By contrast, dopaminergic VTA neurons
that did not project to M1 were activated by both skilled reaching and food
rewards. Non-dopaminergic neurons were found to be activated by motor task
performance at plateau, but not during skill acquisition. These results indicate
that distinct populations of VTA neurons are activated by motor skill acquisition
and task performance. Moreover, this activation is not merely related to
consumption of food rewards.
PMID- 29330489
TI - Decoding hind limb kinematics from neuronal activity of the dorsal horn neurons
using multiple level learning algorithm.
AB - Decoding continuous hind limb joint angles from sensory recordings of neural
system provides a feedback for closed-loop control of hind limb movement using
functional electrical stimulation. So far, many attempts have been done to
extract sensory information from dorsal root ganglia and sensory nerves. In this
work, we examine decoding joint angles trajectories from the single-electrode
extracellular recording of dorsal horn gray matter of the spinal cord during
passive limb movement in anesthetized cats. In this study, a processing framework
based on ensemble learning approach is propose to combine firing rate (FR) and
interspike interval (ISI) information of the neuronal activity. For this purpose,
a stacked generalization approach based on recurrent neural network is proposed
to enhance decoding accuracy of the movement kinematics. The results show that
the high precision neural decoding of limb movement can be achieved even with a
single electrode implanted in the spinal cord gray matter.
PMID- 29330491
TI - Application of Hydrazine-Embedded Heterocyclic Compounds to High Voltage
Rechargeable Lithium Organic Batteries.
AB - Hydrazine-embedded heterocyclic compounds with dimeric dimethylacridine (1b),
carbazole (2b), and phenothiazine (3b) skeletons were applied to cathode active
materials of rechargeable lithium organic batteries, and the performance of the
batteries was evaluated. The charge/discharge curves exhibited clear plateaus in
the high voltage range of 3.3-3.7 V. The capacities of the plateau regions were
comparable to the calculated capacities corresponding to the one-electron redox
of the molecules. The amount of the active compound 3b could be increased up to
30 wt% in the electrode composite, and fast charge/discharge performance was also
observed.
PMID- 29330490
TI - Differentially expressed microRNAs between cattleyak and yak testis.
AB - Cattleyak are interspecific hybrids between cattle and yak, exhibiting the same
prominent adaptability as yak and much higher performances than yak. However,
male infertility of cattleyak resulted from spermatogenic arrest has greatly
restricted their effective utilization in yak breeding. In past decades, much
work has been done to investigate the mechanisms of spermatogenic arrest, but
little is known about the differences of the post-transcriptional regulators
between cattleyak and yak, which may contribute to the impaired spermatogenesis.
MiRNAs, a class of endogenous non-coding small RNA, were revealed to play crucial
roles in regulating gene expression at post-transcriptional level. In the present
study, we identified 50 differentially expressed (DE) known miRNAs and 11 novel
miRNAs by using Illumina HISeq and bioinformatic analysis. A total of 50 putative
target sites for the 13 DE known miRNAs and 30 for the 6 DE novel miRNAs were
identified, respectively. GO and KEGG analyses were performed to reveal the
functions of target genes for DE miRNAs. In addition, RT-qPCR was performed to
validate the expression of the DE miRNAs and its targets. The identification of
these miRNAs may provide valuable information for a better understanding of
spermatogenic arrest in cattleyak.
PMID- 29330492
TI - Turning a normal microscope into a super-resolution instrument using a scanning
microlens array.
AB - We report dielectric microsphere array-based optical super-resolution microscopy.
A dielectric microsphere that is placed on a sample is known to generate a
virtual image with resolution better than the optical diffraction limit. However,
a limitation of such type of super-resolution microscopy is the restricted field
of-view, essentially limited to the central area of the microsphere-generated
image. We overcame this limitation by scanning a micro-fabricated array of
ordered microspheres over the sample using a customized algorithm that moved step
by-step a motorized stage, meanwhile the microscope-mounted camera was taking
pictures at every step. Finally, we stitched together the extracted central parts
of the virtual images that showed super-resolution into a mosaic image. We
demonstrated 130 nm lateral resolution (~lambda/4) and 5 * 105 um2 scanned
surface area using a two by one array of barium titanate glass microspheres in
oil-immersion environment. Our findings may serve as a basis for widespread
applications of affordable optical super-resolution microscopy.
PMID- 29330493
TI - Development of versatile non-homologous end joining-based knock-in module for
genome editing.
AB - CRISPR/Cas9-based genome editing has dramatically accelerated genome engineering.
An important aspect of genome engineering is efficient knock-in technology. For
improved knock-in efficiency, the non-homologous end joining (NHEJ) repair
pathway has been used over the homology-dependent repair pathway, but there
remains a need to reduce the complexity of the preparation of donor vectors. We
developed the versatile NHEJ-based knock-in module for genome editing (VIKING).
Using the consensus sequence of the time-honored pUC vector to cut donor vectors,
any vector with a pUC backbone could be used as the donor vector without
customization. Conditions required to minimize random integration rates of the
donor vector were also investigated. We attempted to isolate null lines of the
VDR gene in human HaCaT keratinocytes using knock-in/knock-out with a selection
marker cassette, and found 75% of clones isolated were successfully knocked-in.
Although HaCaT cells have hypotetraploid genome composition, the results suggest
multiple clones have VDR null phenotypes. VIKING modules enabled highly efficient
knock-in of any vectors harboring pUC vectors. Users now can insert various
existing vectors into an arbitrary locus in the genome. VIKING will contribute to
low-cost genome engineering.
PMID- 29330495
TI - Large unexplained suite of chemically reactive compounds present in ambient air
due to biomass fires.
AB - Biomass fires impact global atmospheric chemistry. The reactive compounds emitted
and formed due to biomass fires drive ozone and organic aerosol formation,
affecting both air quality and climate. Direct hydroxyl (OH) Reactivity
measurements quantify total gaseous reactive pollutant loadings and comparison
with measured compounds yields the fraction of unmeasured compounds. Here, we
quantified the magnitude and composition of total OH reactivity in the north-west
Indo-Gangetic Plain. More than 120% increase occurred in total OH reactivity (28
s-1 to 64 s-1) and from no missing OH reactivity in the normal summertime air,
the missing OH reactivity fraction increased to ~40 % in the post-harvest
summertime period influenced by large scale biomass fires highlighting presence
of unmeasured compounds. Increased missing OH reactivity between the two
summertime periods was associated with increased concentrations of compounds with
strong photochemical source such as acetaldehyde, acetone, hydroxyacetone,
nitromethane, amides, isocyanic acid and primary emissions of acetonitrile and
aromatic compounds. Currently even the most detailed state-of-the art atmospheric
chemistry models exclude formamide, acetamide, nitromethane and isocyanic acid
and their highly reactive precursor alkylamines (e.g. methylamine, ethylamine,
dimethylamine, trimethylamine). For improved understanding of atmospheric
chemistry-air quality-climate feedbacks in biomass-fire impacted atmospheric
environments, future studies should include these compounds.
PMID- 29330494
TI - Characterizing the bacterial microbiota in different gastrointestinal tract
segments of the Bactrian camel.
AB - The bacterial community plays important roles in the gastrointestinal tracts
(GITs) of animals. However, our understanding of the microbial communities in the
GIT of Bactrian camels remains limited. Here, we describe the bacterial
communities from eight different GIT segments (rumen, reticulum, abomasum,
duodenum, ileum, jejunum, caecum, colon) and faeces determined from 11 Bactrian
camels using 16S rRNA gene amplicon sequencing. Twenty-seven bacterial phyla were
found in the GIT, with Firmicutes, Verrucomicrobia and Bacteroidetes
predominating. However, there were significant differences in microbial community
composition between segments of the GIT. In particular, a greater proportion of
Akkermansia and Unclassified Ruminococcaceae were found in the large intestine
and faecal samples, while more Unclassified Clostridiales and Unclassified
Bacteroidales were present in the in forestomach and small intestine. Comparative
analysis of the microbiota from different GIT segments revealed that the
microbial profile in the large intestine was like that in faeces. We also
predicted the metagenomic profiles for the different GIT regions. In forestomach,
there was enrichment associated with replication and repair and amino acid
metabolism, while carbohydrate metabolism was enriched in the large intestine and
faeces. These results provide profound insights into the GIT microbiota of
Bactrian camels.
PMID- 29330496
TI - Framing Continental Shelf Waves in the southern Adriatic Sea, a further flushing
factor beyond dense water cascading.
AB - Continental Shelf Waves (CSWs) are oscillatory phenomena migrating along the
continental margins, controlled by the interplay of rotation and bathymetric
gradients. Here we combine observational data from five moored current meters and
high-resolution hydrodynamic model fields for describing the generation and
propagation of CSWs along the Southern Adriatic Margin (SAM, eastern
Mediterranean Sea), where the possibility of their occurrence has been
theoretically hypothesised but not experimentally observed up to now. Results
show that in spring 2012 a train of CSWs with 35-87 km wavelength and 2-4 day
period was generated on the northern sectors of the SAM and propagated southwards
along its western slope. Along their path, CSWs modify their apparent frequency
and oscillation mode as an effect of the background current and scattering caused
by changes in the continental margin morphology. This signal appears as a
persistent feature triggered by the inflow of a dense water vein formed in the
northern Adriatic Sea, propagating upwelling and downwelling patterns along broad
sectors of the continental slope. CSWs thus appear as an additional remote
controlled mechanism for cross-shelf exchange of water, sediment and nutrients in
the SAM, besides the well-acknowledged dense water downflow along preferential
pathways driven by local topographic constraints.
PMID- 29330498
TI - Replication of biocompatible, nanotopographic surfaces.
AB - The ability of cells to sense and respond to nanotopography is being implicated
as a key element in many physiological processes such as cell differentiation,
immune response, and wound healing, as well as in pathologies such as cancer
metastasis. To understand how nanotopography affects cellular behaviors, new
techniques are required for the mass production of biocompatible, rigid
nanotopographic surfaces. Here we introduce a method for the rapid and
reproducible production of biocompatible, rigid, acrylic nanotopographic
surfaces, and for the functionalization of the surfaces with adhesion-promoting
molecules for cell experiments. The replica surfaces exhibit high optical
transparency, which is advantageous for high-resolution, live-cell imaging. As a
representative application, we demonstrate that epithelial cells form focal
adhesions on surfaces composed of nanoscale ridges and grooves, and that the
focal adhesions prefer to localize on the nanoridges. We further demonstrate that
both F-actin and microtubules align along the nanoridges, but only F-actin aligns
along the nanogrooves. The mass production of nanotopographic surfaces opens the
door to the investigation of the effect of physical cues on the spatial
distribution and the dynamics of intracellular proteins, and to the study of the
mechanism of mechanosensing in processes such as cell migration, phagocytosis,
division, and differentiation.
PMID- 29330497
TI - Visual learning with reduced adaptation is eccentricity-specific.
AB - Visual learning is known to be specific to the trained target location, showing
little transfer to untrained locations. Recently, learning was shown to transfer
across equal-eccentricity retinal-locations when sensory adaptation due to
repetitive stimulation was minimized. It was suggested that learning transfers to
previously untrained locations when the learned representation is location
invariant, with sensory adaptation introducing location-dependent
representations, thus preventing transfer. Spatial invariance may also fail when
the trained and tested locations are at different distance from the center of
gaze (different retinal eccentricities), due to differences in the corresponding
low-level cortical representations (e.g. allocated cortical area decreases with
eccentricity). Thus, if learning improves performance by better classifying
target-dependent early visual representations, generalization is predicted to
fail when locations of different retinal eccentricities are trained and tested in
the absence sensory adaptation. Here, using the texture discrimination task, we
show specificity of learning across different retinal eccentricities (4-8 degrees
) using reduced adaptation training. The existence of generalization across equal
eccentricity locations but not across different eccentricities demonstrates that
learning accesses visual representations preceding location independent
representations, with specificity of learning explained by inhomogeneous sensory
representation.
PMID- 29330499
TI - Three-Dimensional Physical Model-Assisted Planning and Navigation for
Laparoscopic Partial Nephrectomy in Patients with Endophytic Renal Tumors.
AB - Resection of completely endophytic renal tumors is a huge challenge for surgeons
due to a lack of definite visual clues, especially in the laparoscopic approach.
Three-dimensional (3D) kidney models, which can illustrate the clear relationship
between renal masses and surrounding health tissues, were considered as reliable
tools for understanding renal tumor characteristics in previous studies. We
hypothesized that 3D kidney models can be used not only for planning but also for
navigating laparoscopic partial nephrectomy (LPN) in patients with completely
endophytic renal tumors. In this study, we successfully constructed five cases of
3D kidney models for assisted planning and navigation for LPN in endophytic renal
tumors. The renal masses and surrounding normal parenchyma of the patient
specific 3D models were dyed by different colorants for clear illustration. All
patients experienced acceptable perioperative outcomes, and no patient suffered
serious relative complications. The 3D kidney models were considered as a
reliable tool based on clinical outcome and postoperative questionnaire results.
This study is the first report of 3D kidney models for patients with completely
endophytic tumors. 3D kidney models can aid surgeons in understanding the
characteristics of renal tumors and potentially support assisted planning and
performance of LPN in endophytic tumor cases.
PMID- 29330501
TI - Novel endogenous simian retroviral integrations in Vero cells: implications for
quality control of a human vaccine cell substrate.
AB - African green monkey (AGM)-derived Vero cells have been utilized to produce
various human vaccines. The Vero cell genome harbors a variety of simian
endogenous type D retrovirus (SERV) sequences. In this study, a transcriptome
analysis showed that DNA hypomethylation released the epigenetic repression of
SERVs in Vero cells. Moreover, comparative genomic analysis of three Vero cell
sublines and an AGM reference revealed that the genomes of the sublines have ~80
SERV integrations. Among them, ~60 integrations are present within all three cell
sublines and absent from the reference sequence. At least several of these
integrations consist of complete SERV proviruses. These results strongly suggest
that SERVs integrated in the genome of Vero cells did not retrotranspose after
the establishment of the cell lineage as far as cells were maintained under
standard culture and passage conditions, providing a scientific basis for
controlling the quality of pharmaceutical cell substrates and their derived
biologics.
PMID- 29330500
TI - Integration of GWAS, pathway and network analyses reveals novel mechanistic
insights into the synthesis of milk proteins in dairy cows.
AB - The quantities and proportions of protein fractions have notable effects on the
nutritional and technological value of milk. Although much is known about the
effects of genetic variants on milk proteins, the complex relationships among the
set of genes and pathways regulating the different protein fractions synthesis
and secretion into milk in dairy cows are still not completely understood. We
conducted genome-wide association studies (GWAS) for milk nitrogen fractions in a
cohort of 1,011 Brown Swiss cows, which uncovered 170 significant single
nucleotide polymorphism (SNPs), mostly located on BTA6 and BTA11. Gene-set
analysis and the network-based Associated Weight Matrix approach revealed that
the milk proteins associated genes were involved in several biological functions,
particularly ion and cation transmembrane transporter activity and neuronal and
hormone signalling, according to the structure and function of casein micelles.
Deeper analysis of the transcription factors and their predicted target genes
within the network revealed that GFI1B, ZNF407 and NR5A1 might act as master
regulators of milk protein synthesis and secretion. The information acquired
provides novel insight into the regulatory mechanisms controlling milk protein
synthesis and secretion in bovine mammary gland and may be useful in breeding
programmes aimed at improving milk nutritional and/or technological properties.
PMID- 29330503
TI - Effects of larvae density and food concentration on Crown-of-Thorns seastar
(Acanthaster cf. solaris) development in an automated flow-through system.
AB - Coral-eating Crown-of-Thorns Sea stars (Acanthaster spp.) are major contributors
to coral reef loss in the Indo-Pacific region. A release from food limitation of
their planktotrophic larvae through enhanced pelagic productivity is one of the
main hypothesis explaining population outbreaks ('nutrient limitation
hypothesis'). To improve the understanding of these outbreaks we developed an
automated flow- through larvae rearing system that maintained food (microalgae)
at set levels over the course of four 15d experiments. This resulted in stable
food concentrations in experimental tanks. Increased algae concentrations had a
significant positive effect on larval development and size at 10 and 15 days post
fertilization (dpf). Larvae densities had no effect at 10 dpf. At 15 dpf greater
larvae densities were associated with declines in larvae size. Larval development
was slowed under higher larvae densities. Thus, the effects of algae
concentration and larvae density were additive at 15 dpf, with larvae under low
densities at a given algae concentration being further developed than those under
higher densities. The development of a flow-through system gives greater insight
into the effect of algae and larvae concentrations on Acanthaster development,
and the system can be applied to further test the nutrient-limitation hypothesis
for present and future outbreaks.
PMID- 29330502
TI - Targeting Insulin-Like Growth Factor-I and Extracellular Matrix Interactions in
Melanoma Progression.
AB - Insulin-like growth factor (IGF)-I binds to the ECM protein vitronectin (VN)
through IGF binding proteins (IGFBPs) to enhance proliferation and migration of
skin keratinocytes and fibroblasts. Although evidence exists for the role of
individual components of the complex (IGF-I, IGFBP-3 and VN), the cellular
functions stimulated by these proteins together as a complex remains un
investigated in melanoma cells. We report here that the IGF-I:IGFBP-3:VN trimeric
complex stimulates a dose-dependent increase in the proliferation and migration
of WM35 and Sk-MEL28 melanoma cells. In 3D MatrigelTM and hydrogel cultures, both
cell lines formed primary tumor-like spheroids, which increased in size in a dose
dependent manner in response to the trimeric complex. Furthermore, we reveal
IGFBP-3:VN protein complexes in malignant melanoma and squamous cell carcinoma
patient tissues, where the IGFBP-3:VN complex was seen to be predominantly tumor
cell-associated. Peptide antagonists designed to target the binding of IGF
I:IGFBP-3 to VN were demonstrated to inhibit IGF-I:IGFBP-3:VN-stimulated cell
migration, invasion and 3D tumor cell growth of melanoma cells. Overall, this
study provides new data on IGF:ECM interactions in skin malignancies and
demonstrates the potential usefulness of a growth factor:ECM-disrupting strategy
for abrogating tumor progression.
PMID- 29330504
TI - Unique Roles of beta-Arrestin in GPCR Trafficking Revealed by Photoinducible
Dimerizers.
AB - Intracellular trafficking of G protein-coupled receptors (GPCRs) controls their
localization and degradation, which affects a cell's ability to adapt to
extracellular stimuli. Although the perturbation of trafficking induces important
diseases, these trafficking mechanisms are poorly understood. Herein, we
demonstrate an optogenetic method using an optical dimerizer, cryptochrome (CRY)
and its partner protein (CIB), to analyze the trafficking mechanisms of GPCRs and
their regulatory proteins. Temporally controlling the interaction between beta
arrestin and beta2-adrenergic receptor (ADRB2) reveals that the duration of the
beta-arrestin-ADRB2 interaction determines the trafficking pathway of ADRB2.
Remarkably, the phosphorylation of ADRB2 by G protein-coupled receptor kinases is
unnecessary to trigger clathrin-mediated endocytosis, and beta-arrestin
interacting with unphosphorylated ADRB2 fails to activate mitogen-activated
protein kinase (MAPK) signaling, in contrast to the ADRB2 agonist isoproterenol.
Temporal control of beta-arrestin-GPCR interactions will enable the investigation
of the unique roles of beta-arrestin and the mechanism by which it regulates beta
arrestin-specific trafficking pathways of different GPCRs.
PMID- 29330505
TI - Over-expression of a retinol dehydrogenase (SRP35/DHRS7C) in skeletal muscle
activates mTORC2, enhances glucose metabolism and muscle performance.
AB - SRP-35 is a short-chain dehydrogenase/reductase belonging to the DHRS7C
dehydrogenase/ reductase family 7. Here we show that its over-expression in mouse
skeletal muscles induces enhanced muscle performance in vivo, which is not
related to alterations in excitation-contraction coupling but rather linked to
enhanced glucose metabolism. Over-expression of SRP-35 causes increased
phosphorylation of AktS473, triggering plasmalemmal targeting of GLUT4 and higher
glucose uptake into muscles. SRP-35 signaling involves RARalpha and RARgamma (non
genomic effect), PI3K and mTORC2. We also demonstrate that all-trans retinoic
acid, a downstream product of the enzymatic activity of SRP-35, mimics the effect
of SRP-35 in skeletal muscle, inducing a synergistic effect with insulin on
AKTS473 phosphorylation. These results indicate that SRP-35 affects skeletal
muscle metabolism and may represent an important target for the treatment of
metabolic diseases.
PMID- 29330506
TI - Impact of wave whitecapping on land falling tropical cyclones.
AB - Predicting tropical cyclone structure and evolution remains challenging.
Particularly, the surface wave interactions with the continental shelf and their
impact on tropical cyclones have received very little attention. Through a series
of state-of-the-art high-resolution, fully-coupled ocean-wave and atmosphere
ocean-wave experiments, we show here, for the first time, that in presence of
continental shelf waves can cause substantial cooling of the sea surface. Through
whitecapping there is a transfer of momentum from the surface which drives deeper
vertical mixing. It is the waves and not just the wind which become the major
driver of stratified coastal ocean ahead-of-cyclone cooling. In the fully-coupled
atmosphere-ocean-wave model a negative feedback is found. The maximum wind speed
is weaker and the damaging footprint area of hurricane-force winds is reduced by
up to 50% due to the strong wave induced ocean cooling ahead. Including wave
ocean coupling is important to improve land falling tropical cyclone intensity
predictions for the highly populated and vulnerable coasts.
PMID- 29330508
TI - Picometer polar atomic displacements in strontium titanate determined by resonant
X-ray diffraction.
AB - Physical properties of crystalline materials often manifest themselves as atomic
displacements either away from symmetry positions or driven by external fields.
Especially the origin of multiferroic or magnetoelectric effects may be hard to
ascertain as the related displacements can reach the detection limit. Here we
present a resonant X-ray crystal structure analysis technique that shows enhanced
sensitivity to minute atomic displacements. It is applied to a recently found
crystalline modification of strontium titanate that forms in single crystals
under electric field due to oxygen vacancy migration. The phase has demonstrated
unexpected properties, including piezoelectricity and pyroelectricity, which can
only exist in non-centrosymmetric crystals. Apart from that, the atomic structure
has remained elusive and could not be obtained by standard methods. Using
resonant X-ray diffraction, we determine atomic displacements with sub-picometer
precision and show that the modified structure of strontium titanate corresponds
to that of well-known ferroelectrics such as lead titanate.
PMID- 29330507
TI - Uncovering the anticancer mechanism of Compound Kushen Injection against HCC by
integrating quantitative analysis, network analysis and experimental validation.
AB - Compound Kushen Injection (CKI) is a Traditional Chinese Medicine (TCM)
preparation that has been clinically used in China to treat various types of
solid tumours. Although several studies have revealed that CKI can inhibit the
proliferation of hepatocellular carcinoma (HCC) cell lines, the active compounds,
potential targets and pathways involved in these effects have not been
systematically investigated. Here, we proposed a novel idea of "main active
compound-based network pharmacology" to explore the anti-cancer mechanism of CKI.
Our results showed that CKI significantly suppressed the proliferation and
migration of SMMC-7721 cells. Four main active compounds of CKI (matrine,
oxymatrine, sophoridine and N-methylcytisine) were confirmed by the integration
of ultra-performance liquid chromatography/mass spectrometry (UPLC-MS) with cell
proliferation assays. The potential targets and pathways involved in the anti-HCC
effects of CKI were predicted by a network pharmacology approach, and some of the
crucial proteins and pathways were further validated by western blotting and
metabolomics approaches. Our results indicated that CKI exerted anti-HCC effects
via the key targets MMP2, MYC, CASP3, and REG1A and the key pathways of
glycometabolism and amino acid metabolism. These results provide insights into
the mechanism of CKI by combining quantitative analysis of components, network
pharmacology and experimental validation.
PMID- 29330509
TI - Transcriptome analysis reveals carbohydrate-mediated liver immune responses in
Epinephelus akaara.
AB - As the cheapest energy source, carbohydrates are used in fish feeds to improve
physical quality and reduce catabolism of proteins and lipids. The liver is the
primary organ for metabolism and is also an important site of immune regulation.
Here, we investigated the effect of different dietary carbohydrate levels on
growth and health by evaluating the liver transcriptome of Epinephelus akaara. In
this study, E. akaara juveniles were fed diets containing few (0% corn starch),
moderate (18% corn starch), and high (30% corn starch) levels of dietary
carbohydrate. After an 8-week feeding trial, E. akaara fed 30% dietary
carbohydrates exhibited poor growth performance compared with those fed 0% and
18% dietary carbohydrates (P > 0.05). Genes related to the immune system,
including IL8, TLR9, CXCR4, CCL4, and NFkappaB inhibitor alpha, were over
expressed in E. akaara fed the highest level of carbohydrate (30%). This general
over-expression could indicate activation of inflammatory processes in the liver.
The liver transcriptome data of E. akaara reported here indicate that high
carbohydrate level of diet can lead to poor growth and inflammatory immune
response in E. akaara.
PMID- 29330510
TI - Shaping and Controlled Fragmentation of Liquid Metal Droplets through Cavitation.
AB - Targeting micrometer sized metal droplets with near-infrared sub-picosecond laser
pulses generates intense stress-confined acoustic waves within the droplet.
Spherical focusing amplifies their pressures. The rarefaction wave nucleates
cavitation at the center of the droplet, which explosively expands with a
repeatable fragmentation scenario resulting into high-speed jetting. We predict
the number of jets as a function of the laser energy by coupling the cavitation
bubble dynamics with Rayleigh-Taylor instabilities. This provides a path to
control cavitation and droplet shaping of liquid metals in particular for their
use as targets in extreme-UV light sources.
PMID- 29330511
TI - Testing density-functional approximations on a lattice and the applicability of
the related Hohenberg-Kohn-like theorem.
AB - We present a metric-space approach to quantify the performance of approximations
in lattice density-functional theory for interacting many-body systems and to
explore the regimes where the Hohenberg-Kohn-type theorem on fermionic lattices
is applicable. This theorem demonstrates the existence of one-to-one mappings
between particle densities, wave functions and external potentials. We then focus
on these quantities, and quantify how far apart in metric space the approximated
and exact ones are. We apply our method to the one-dimensional Hubbard model for
different types of external potentials, and assess the regimes where it is
applicable to one of the most used approximations in density-functional theory,
the local density approximation (LDA). We find that the potential distance may
have a very different behaviour from the density and wave function distances, in
some cases even providing the wrong assessments of the LDA performance trends. We
attribute this to the systems reaching behaviours which are borderline for the
applicability of the one-to-one correspondence between density and external
potential. On the contrary the wave function and density distances behave
similarly and are always sensitive to system variations. Our metric-based method
correctly predicts the regimes where the LDA performs fairly well and the regimes
where it fails. This suggests that our method could be a practical tool for
testing the efficiency of density-functional approximations.
PMID- 29330512
TI - Inactivated rotavirus vaccine by parenteral administration induces mucosal
immunity in mice.
AB - To improve the safety and efficacy of oral rotavirus vaccines, we developed an
inactivated rotavirus vaccine (IRV) for parenteral administration. Since it
remains unknown whether parenteral vaccination can induce mucosal immunity, we
performed a comprehensive assessment of immune responses to IRV in mice with an
adjuvant-free dissolving polymer MN patch or by alum-adjuvanted IM injection. We
demonstrated that IRV induced the expression of the gut homing receptor LPAM-1 on
T and B cells in spleen and mLN of vaccinated mice. MN patch IRV vaccination
induced a slight Th1 phenotype while IM vaccination induced a balanced Th1/Th2
phenotype. In addition, a dose-sparing effect was seen for rotavirus-specific
serum IgG and neutralizing activity for both vaccination routes. Our study is the
first to show that parenterally administered IRV can induce mucosal immunity in
the gut, in addition to strong serum antibody response, and is a promising
candidate vaccine in achieving global immunization against rotavirus.
PMID- 29330513
TI - Magnetic and structural properties of glass-coated Heusler-type microwires
exhibiting martensitic transformation.
AB - We have studied magnetic and structural properties of the Heusler-type Ni-Mn-Ga
glass-coated microwires prepared by Tailor-Ulitovsky technique. As-prepared
sample presents magnetoresistance effect and considerable dependence of
magnetization curves (particularly magnetization values) on magnetic field
attributed to the magnetic and atomic disorder. Annealing strongly affects the
temperature dependence of magnetization and Curie temperature of microwires.
After annealing of the microwires at 973 K, the Curie temperature was enhanced to
about 280 K which is beneficial for the magnetic solid state refrigeration. The
observed hysteretic anomalies on the temperature dependences of resistance and
magnetization in the as-prepared and annealed samples are produced by the
martensitic transformation. The magnetoresistance and magnetocaloric effects have
been investigated to illustrate a potential technological capability of studied
microwires.
PMID- 29330514
TI - A comparison of static and dynamic cerebral autoregulation during mild whole-body
cold stress in individuals with and without cervical spinal cord injury: a pilot
study.
AB - STUDY DESIGN: Experimental study. OBJECTIVES: To characterize static and dynamic
cerebral autoregulation (CA) of individuals with cervical spinal cord injury
(SCI) compared to able-bodied controls in response to moderate increases in mean
arterial pressure (MAP) caused by mild whole-body cold stress. SETTING: Japan
METHODS: Five men with complete autonomic cervical SCI (sustained > 5 y) and six
age-matched able-bodied men participated in hemodynamic, temperature,
catecholamine and respiratory measurements for 60 min during three consecutive
stages: baseline (10 min; 33 degrees C water through a thin-tubed whole-body
suit), mild cold stress (20 min; 25 degrees C water), and post-cold recovery (30
min; 33 degrees C water). Static CA was determined as the ratio between mean
changes in middle cerebral artery blood velocity and MAP, dynamic CA as transfer
function coherence, gain, and phase between spontaneous changes in MAP to middle
cerebral artery blood velocity. RESULTS: MAP increased in both groups during cold
and post-cold recovery (mean differences: 5-10 mm Hg; main effect of time: p =
0.001). Static CA was not different between the able-bodied vs. the cervical SCI
group (mean (95% confidence interval (CI)) of between-group difference: -4 (-11
to 3) and -2 (-5 to 1) cm/s/mm Hg for cold (p = 0.22) and post-cold (p = 0.24),
respectively). At baseline, transfer function phase was shorter in the cervical
SCI group (mean (95% CI) of between-group difference: 0.6 (0.2 to 1.0) rad; p =
0.006), while between-group differences in changes in phase were not different in
response to the cold stress (interaction term: p = 0.06). CONCLUSIONS: This pilot
study suggests that static CA is similar between individuals with cervical SCI
and able-bodied controls in response to moderate increases in MAP, while dynamic
CA may be impaired in cervical SCI because of disturbed sympathetic control.
PMID- 29330515
TI - HyphaTracker: An ImageJ toolbox for time-resolved analysis of spore germination
in filamentous fungi.
AB - The dynamics of early fungal development and its interference with physiological
signals and environmental factors is yet poorly understood. Especially
computational analysis tools for the evaluation of the process of early spore
germination and germ tube formation are still lacking. For the time-resolved
analysis of conidia germination of the filamentous ascomycete Fusarium fujikuroi
we developed a straightforward toolbox implemented in ImageJ. It allows for
processing of microscopic acquisitions (movies) of conidial germination starting
with drift correction and data reduction prior to germling analysis. From the
image time series germling related region of interests (ROIs) are extracted,
which are analysed for their area, circularity, and timing. ROIs originating from
germlings crossing other hyphae or the image boundaries are omitted during
analysis. Each conidium/hypha is identified and related to its origin, thus
allowing subsequent categorization. The efficiency of HyphaTracker was proofed
and the accuracy was tested on simulated germlings at different signal-to-noise
ratios. Bright-field microscopic images of conidial germination of rhodopsin
deficient F. fujikuroi mutants and their respective control strains were analysed
with HyphaTracker. Consistent with our observation in earlier studies the CarO
deficient mutant germinated earlier and grew faster than other, CarO expressing
strains.
PMID- 29330516
TI - Drinking by amphibious fish: convergent evolution of thirst mechanisms during
vertebrate terrestrialization.
AB - Thirst aroused in the forebrain by angiotensin II (AngII) or buccal drying
motivates terrestrial vertebrates to search for water, whereas aquatic fish can
drink surrounding water only by reflex swallowing generated in the hindbrain.
Indeed, AngII induces drinking through the hindbrain even after removal of the
whole forebrain in aquatic fish. Here we show that AngII induces thirst also in
the amphibious mudskipper goby without direct action on the forebrain, but
through buccal drying. Intracerebroventricular injection of AngII motivated
mudskippers to move into water and drink as with tetrapods. However, AngII
primarily increased immunoreactive c-Fos at the hindbrain swallowing center where
AngII receptors were expressed, as in other ray-finned fish, and such direct
action on the forebrain was not found. Behavioural analyses showed that loss of
buccal water on land by AngII-induced swallowing, by piercing holes in the
opercula, or by water-absorptive gel placed in the cavity motivated mudskippers
to move to water for refilling. Since sensory detection of water at the bucco
pharyngeal cavity like 'dry mouth' has recently been noted to regulate thirst in
mammals, similar mechanisms seem to have evolved in distantly related species in
order to solve osmoregulatory problems during terrestrialization.
PMID- 29330517
TI - Iron-induced calcification in human aortic vascular smooth muscle cells through
interleukin-24 (IL-24), with/without TNF-alpha.
AB - In CKD patients, arteriosclerotic lesions, including calcification, can occur in
vascular smooth muscle cells in a process called Moenckeberg's medial
arteriosclerosis. Iron overload induces several complications, including the
acceleration of arteriosclerosis. However, the relationship between Moenckeberg's
arteriosclerosis in vascular smooth muscle cells and iron accumulation has
remained unknown. We tested the accelerated effect of iron on calcification in
cultured human aortic vascular smooth muscle cells (HASMCs). After establishment
of this model, we performed a microarray analysis using mRNA from early stage
culture HASMCs after iron stimulation with or without TNF-alpha stimulation. The
role of interleukin-24 (IL-24) was confirmed from candidate genes that might
contribute to calcification. HASMCs demonstrated calcification induced by iron
and TNF-alpha. Calcification of HASMCs was synergistically enhanced by
stimulation with both iron and TNF-alpha. In the early phase of calcification,
microarray analysis revealed up-regulation of IL-24. Stimulation of HASMCs by IL
24 instead of iron induced calcification. The anti-IL-24 antibody reversed the
effect of IL-24, supporting the important role of IL-24 in HASMCs calcification.
In conclusion, iron-induced calcification in vascular smooth muscle cells
occurred via IL-24, IL-24 was increased during the calcification process induced
by iron, and IL-24 itself caused calcification in the absence of iron.
PMID- 29330518
TI - Spartina alterniflora invasion affects soil carbon in a C3 plant-dominated tidal
marsh.
AB - The carbon cycle is significantly affected by Spartina alterniflora invasion
through its impact on blue carbon in many salt marshes. To determine the impacts
on soil organic carbon (SOC), we studied the vertical and horizontal distribution
of SOC. And stable carbon isotopes were used to explore the impact of the age of
S. alterniflora invasion on SOC in Chongming Dongtan wetland located in the
Yangtze River estuary, China. The results showed that the SOC concentration was
higher in the S. alterniflora community than that in the native Phragmites
australis community. The age of invasion and the SOC concentration increased with
increasing elevation, while the SOC concentration decreased with increasing soil
depth. The delta13C value became less negative at greater depth, which was
related to the contribution from 13C- enriched carbon sources after 3 years of
invasion. After 7 and 10 years, the delta13C value became more negative at
greater depth in both communities. S. alterniflora had a positive effect on the
soil carbon pool, and its contribution was related to soil depth. In the low
tidal marshes, the contribution of S. alterniflora was negatively correlated with
soil depth, while it was positively correlated with soil depth in the high tidal
marshes. The results from this study will contribute to improved understanding of
future ecological consequences.
PMID- 29330519
TI - Large-scale aggregation analysis of eukaryotic proteins reveals an involvement of
intrinsically disordered regions in protein folding.
AB - A subset of the proteome is prone to aggregate formation, which is prevented by
chaperones in the cell. To investigate whether the basic principle underlying the
aggregation process is common in prokaryotes and eukaryotes, we conducted a large
scale aggregation analysis of ~500 cytosolic budding yeast proteins using a
chaperone-free reconstituted translation system, and compared the obtained data
with that of ~3,000 Escherichia coli proteins reported previously. Although the
physicochemical properties affecting the aggregation propensity were generally
similar in yeast and E. coli proteins, the susceptibility of aggregation in yeast
proteins were positively correlated with the presence of intrinsically disordered
regions (IDRs). Notably, the aggregation propensity was not significantly changed
by a removal of IDRs in model IDR-containing proteins, suggesting that the
properties of ordered regions in these proteins are the dominant factors for
aggregate formation. We also found that the proteins with longer IDRs were
disfavored by E. coli chaperonin GroEL/ES, whereas both bacterial and yeast
Hsp70/40 chaperones have a strong aggregation-prevention effect even for proteins
possessing IDRs. These results imply that a key determinant to discriminate the
eukaryotic proteomes from the prokaryotic proteomes in terms of protein folding
would be the attachment of IDRs.
PMID- 29330520
TI - Association of Homocysteine with Aysmptomatic Intracranial and Extracranial
Arterial Stenosis in Hypertension Patients.
AB - Elevated plasma homocysteine (Hcy) is suggested as an independent risk factor for
stroke. We aimed to investigate the association of Hcy concentration with
intracranial atherosclerosis (ICAS) and extracranial AS (ECAS) in hypertensive
patients without stroke in Chinese population and to explore modified effect of
methylenetetrahydrofolate reductase (MTHFR) C677T on their relationship. The
stenosis of intracranial and extracranial arteries were evaluated in a total of
929 subjects through computerized tomographic angiography (CTA) from aortic arch
to the skull base. Hcy concentration showed significantly association with both
ICAS (OR: 1.105; 95% CI: 1.057-1.155) and ECAS (OR: 1.096; 95% CI: 1.047-1.146)
for 1 umol/L increment in Hcy. Meanwhile, hyperhomocysteinemia (>=15 umol/L) was
also displayed association with ICAS (OR: 1.587; 95% CI: 1.029-2.446) and ECAS
(OR: 2.164; 95% CI: 1.392-3.364) after fully adjustment. Furthermore, in the
subgroup analysis, such association remained significant only in the subjects
that were younger, with normal renal function and with MTHFR 677 C allele. Our
study showed the significant association of Hcy with ECAS and ICAS in
asymptomatic hypertension patients. Hcy played a universal effect on the cervico
cerebral atherosclerosis. Such association was modified by the MTHFR C677T
genotype.
PMID- 29330521
TI - RGS7 is recurrently mutated in melanoma and promotes migration and invasion of
human cancer cells.
AB - Analysis of 501 melanoma exomes revealed RGS7, which encodes a GTPase
accelerating protein (GAP), to be a tumor-suppressor gene. RGS7 was mutated in
11% of melanomas and was found to harbor three recurrent mutations (p.R44C,
p.E383K and p.R416Q). Structural modeling of the most common recurrent mutation
of the three (p.R44C) predicted that it destabilizes the protein due to the loss
of an H-bond and salt bridge network between the mutated position and the serine
and aspartic acid residues at positions 58 as 61, respectively. We experimentally
confirmed this prediction showing that the p.R44C mutant protein is indeed
destabilized. We further show RGS7 p.R44C has weaker catalytic activity for its
substrate Galphao, thus providing a dual mechanism for its loss of function. Both
of these effects are expected to contribute to loss of function of RGS7 resulting
in increased anchorage-independent growth, migration and invasion of melanoma
cells. By mutating position 56 in the R44C mutant from valine to cysteine,
thereby enabling the formation of a disulfide bridge between the two mutated
positions, we slightly increased the catalytic activity and reinstated protein
stability, leading to the rescue of RGS7's function as a tumor suppressor. Our
findings identify RGS7 as a novel melanoma driver and point to the clinical
relevance of using strategies to stabilize the protein and, thereby, restore its
function.
PMID- 29330522
TI - The RacGAP beta-Chimaerin is essential for cerebellar granule cell migration.
AB - During mammalian cerebellar development, postnatal granule cell progenitors
proliferate in the outer part of the External Granule Layer (EGL). Postmitotic
granule progenitors migrate tangentially in the inner EGL before switching to
migrate radially inward, past the Purkinje cell layer, to achieve their final
position in the mature Granule Cell Layer (GCL). Here, we show that the RacGAP
beta-chimaerin is expressed by a small population of late-born, premigratory
granule cells. beta-chimaerin deficiency causes a subset of granule cells to
become arrested in the EGL, where they differentiate and form ectopic neuronal
clusters. These clusters of granule cells are able to recruit aberrantly
projecting mossy fibers. Collectively, these data suggest a role for beta
chimaerin as an intracellular mediator of Cerebellar Granule Cell radial
migration.
PMID- 29330523
TI - Closed-loop control of zebrafish behaviour in three dimensions using a robotic
stimulus.
AB - Robotics is continuously being integrated in animal behaviour studies to create
customizable, controllable, and repeatable stimuli. However, few systems have
capitalized on recent breakthroughs in computer vision and real-time control to
enable a two-way interaction between the animal and the robot. Here, we present a
"closed-loop control" system to investigate the behaviour of zebrafish, a popular
animal model in preclinical studies. The system allows for actuating a
biologically-inspired 3D-printed replica in a 3D workspace, in response to the
behaviour of a zebrafish. We demonstrate the role of closed-loop control in
modulating the response of zebrafish, across a range of behavioural and
information-theoretic measures. Our results suggest that closed-loop control
could enhance the degree of biomimicry of the replica, by increasing the
attraction of live subjects and their interaction with the stimulus. Interactive
experiments hold promise to advance our understanding of zebrafish, offering new
means for high throughput behavioural phenotyping.
PMID- 29330526
TI - Relationship among land surface temperature and LUCC, NDVI in typical karst area.
AB - Land surface temperature (LST) can reflect the land surface water-heat exchange
process comprehensively, which is considerably significant to the study of
environmental change. However, research about LST in karst mountain areas with
complex topography is scarce. Therefore, we retrieved the LST in a karst mountain
area from Landsat 8 data and explored its relationships with LUCC and NDVI. The
results showed that LST of the study area was noticeably affected by altitude and
underlying surface type. In summer, abnormal high-temperature zones were observed
in the study area, perhaps due to karst rocky desertification. LSTs among
different land use types significantly differed with the highest in construction
land and the lowest in woodland. The spatial distributions of NDVI and LST
exhibited opposite patterns. Under the spatial combination of different land use
types, the LST-NDVI feature space showed an obtuse-angled triangle shape and
showed a negative linear correlation after removing water body data. In summary,
the LST can be retrieved well by the atmospheric correction model from Landsat 8
data. Moreover, the LST of the karst mountain area is controlled by altitude,
underlying surface type and aspect. This study provides a reference for land use
planning, ecological environment restoration in karst areas.
PMID- 29330524
TI - NF-kappaB inducing kinase is a therapeutic target for systemic lupus
erythematosus.
AB - NF-kappaB-inducing kinase (NIK) mediates non-canonical NF-kappaB signaling
downstream of multiple TNF family members, including BAFF, TWEAK, CD40, and OX40,
which are implicated in the pathogenesis of systemic lupus erythematosus (SLE).
Here, we show that experimental lupus in NZB/W F1 mice can be treated with a
highly selective and potent NIK small molecule inhibitor. Both in vitro as well
as in vivo, NIK inhibition recapitulates the pharmacological effects of BAFF
blockade, which is clinically efficacious in SLE. Furthermore, NIK inhibition
also affects T cell parameters in the spleen and proinflammatory gene expression
in the kidney, which may be attributable to inhibition of OX40 and TWEAK
signaling, respectively. As a consequence, NIK inhibition results in improved
survival, reduced renal pathology, and lower proteinuria scores. Collectively,
our data suggest that NIK inhibition is a potential therapeutic approach for SLE.
PMID- 29330525
TI - Distinct modulation of inactivation by a residue in the pore domain of voltage
gated Na+ channels: mechanistic insights from recent crystal structures.
AB - Inactivation of voltage-gated Na+ channels (VGSC) is essential for the regulation
of cellular excitability. The molecular rearrangement underlying inactivation is
thought to involve the intracellular linker between domains III and IV serving as
inactivation lid, the receptor for the lid (domain III S4-S5 linker) and the pore
lining S6 segements. To better understand the role of the domain IV S6 segment in
inactivation we performed a cysteine scanning mutagenesis of this region in rNav
1.4 channels and screened the constructs for perturbations in the voltage
dependence of steady state inactivation. This screen was performed in the
background of wild-type channels and in channels carrying the mutation K1237E,
which profoundly alters both permeation and gating-properties. Of all tested
constructs the mutation I1581C was unique in that the mutation-induced gating
changes were strongly influenced by the mutational background. This suggests that
I1581 is involved in specific short-range interactions during inactivation. In
recently published crystal structures VGSCs the respective amino acids homologous
to I1581 appear to control a bend of the S6 segment which is critical to the
gating process. Furthermore, I1581 may be involved in the transmission of the
movement of the DIII voltage-sensor to the domain IV S6 segment.
PMID- 29330527
TI - Aquaglyceroporin PbAQP is required for efficient progression through the liver
stage of Plasmodium infection.
AB - The discovery of aquaglyceroporins (AQP) has highlighted a new mechanism of
membrane solute transport that may hold therapeutic potential for controlling
parasitic infections, including malaria. Plasmodium parasites express a single
AQP at the plasma membrane that functions as a channel for water, nutrients and
waste into and out cells. We previously demonstrated that Plasmodium berghei
targeted for PbAQP deletion are deficient in glycerol import and less virulent
than wild-type parasites during the blood developmental stage. Here, we have
examined the contribution of PbAQP to the infectivity of P. berghei in the liver.
PbAQP is expressed in the sporozoite mosquito stage and is detected at low levels
in intrahepatic parasites at the onset of hepatocyte infection. As the parasites
progress to late hepatic stages, PbAQP transcription increases and PbAQP
localizes to the plasma membrane of hepatic merozoites. Compared to wild-type
parasites, PbAQP-null sporozoites exhibit a delay in blood stage infection due to
slower replication in hepatocytes, resulting in retardation of merosome
production. Furthermore, PbAQP disruption results in a significant reduction in
erythrocyte infectivity by hepatocyte-derived merozoites. Hepatic merozoites
incorporate exogenous glycerol into glycerophospholipids and PbAQP-null
merozoites contain less phosphatidylcholine than wild-type merozoites,
underlining the contribution of Plasmodium AQP to phospholipid syntheses.
PMID- 29330528
TI - Application of Weighted Gene Co-expression Network Analysis for Data from Paired
Design.
AB - Investigating how genes jointly affect complex human diseases is important, yet
challenging. The network approach (e.g., weighted gene co-expression network
analysis (WGCNA)) is a powerful tool. However, genomic data usually contain
substantial batch effects, which could mask true genomic signals. Paired design
is a powerful tool that can reduce batch effects. However, it is currently
unclear how to appropriately apply WGCNA to genomic data from paired design. In
this paper, we modified the current WGCNA pipeline to analyse high-throughput
genomic data from paired design. We illustrated the modified WGCNA pipeline by
analysing the miRNA dataset provided by Shiah et al. (2014), which contains forty
oral squamous cell carcinoma (OSCC) specimens and their matched non-tumourous
epithelial counterparts. OSCC is the sixth most common cancer worldwide. The
modified WGCNA pipeline identified two sets of novel miRNAs associated with OSCC,
in addition to the existing miRNAs reported by Shiah et al. (2014). Thus, this
work will be of great interest to readers of various scientific disciplines, in
particular, genetic and genomic scientists as well as medical scientists working
on cancer.
PMID- 29330530
TI - Estimation of lean body mass by creatinine kinetics increases the prevalence of
muscle wasting in peritoneal dialysis patients compared to bioimpedance.
AB - Dialysis patients are at increased risk for muscle wasting, and time efficient
screening tests are required for to allow for early detection. Creatinine
kinetics have been advocated to estimate lean body mass (LBM) in peritoneal
dialysis (PD) patients, and can be readily calculated in clinical practice from
peritoneal dialysate effluent and urine collections. Bioimpedance is increasingly
available, and we compared methods in 434 PD patients (55% men, 33.3% diabetics),
mean age 55.2 +/- 16.2 years. LBM was lower by creatinine kinetics (47.8 +/- 16.6
kg men, 37.8 +/- 11.2 kg women) vs. bioimpedance (53.2 +/- 11.5 kg men, 39.2 +/-
7.2 kg women), p < 0.01. The prevalence of muscle wasting was much greater using
creatinine kinetics (72.4% men, 52.4% women) vs. bioimpedance (55.2% men, 37.3%),
p < 0.05. Estimates of LBM were much lower using creatinine kinetics compared to
bioimpedance. Studies reporting the prevalence of muscle loss in PD patients will
differ depending upon the method used to estimate muscle mass.
PMID- 29330529
TI - The interaction network of the YidC insertase with the SecYEG translocon, SRP and
the SRP receptor FtsY.
AB - YidC/Oxa1/Alb3 are essential proteins that operate independently or cooperatively
with the Sec machinery during membrane protein insertion in bacteria, archaea and
eukaryotic organelles. Although the interaction between the bacterial SecYEG
translocon and YidC has been observed in multiple studies, it is still unknown
which domains of YidC are in contact with the SecYEG translocon. By in vivo and
in vitro site-directed and para-formaldehyde cross-linking we identified the
auxiliary transmembrane domain 1 of E. coli YidC as a major contact site for SecY
and SecG. Additional SecY contacts were observed for the tightly packed globular
domain and the C1 loop of YidC, which reveals that the hydrophilic cavity of YidC
faces the lateral gate of SecY. Surprisingly, YidC-SecYEG contacts were only
observed when YidC and SecYEG were present at about stoichiometric
concentrations, suggesting that the YidC-SecYEG contact in vivo is either very
transient or only observed for a very small SecYEG sub-population. This is
different for the YidC-SRP and YidC-FtsY interaction, which involves the C1 loop
of YidC and is efficiently observed even at sub-stoichiometric concentrations of
SRP/FtsY. In summary, our data provide a first detailed view on how YidC
interacts with the SecYEG translocon and the SRP-targeting machinery.
PMID- 29330531
TI - Low density neutrophils (LDN) in postoperative abdominal cavity assist the
peritoneal recurrence through the production of neutrophil extracellular traps
(NETs).
AB - Many types of immune cells appear in peritoneal cavity after abdominal surgery.
In patients who underwent laparotomy due to gastric cancer, peritoneal lavages
were obtained before and after surgical procedure. Cells were recovered from
intermediate layer after Ficoll-Hypaque centrifugation and analyzed for
phenotypes and functions, especially focused on low density neutrophils (LDN).
The number of CD66b (+) LDN with mature phenotype was markedly elevated in
postoperative as compared with preoperative lavages. Short term culture of the
purified LDN produced many threadlike structures positive for SYTOX, nucleic acid
staining, as well as histone and myeloperoxidase, suggesting the NETs formation.
Human gastric cancer cells, MKN45, OCUM-1 and NUGC-4, were selectively attached
on the NETs, which was totally abolished by the pretreatment of DNAse I.
Intraperitoneal (IP) co-transfer of the LDN with MKN45 in nude mice strongly
augments the metastasis formation on peritoneum, which was strongly suppressed by
the following IP administration of DNAse I. Many NETs-like structures were
detected on the surface of human omental tissue resected by gastrectomy. NETs on
peritoneal surface can assist the clustering and growth of free tumor cells
disseminated in abdomen. Disruption of the NETs by DNAse might be useful to
prevent the peritoneal recurrence after abdominal surgery.
PMID- 29330532
TI - Methanobactin from Methylosinus trichosporium OB3b inhibits N2O reduction in
denitrifiers.
AB - Methanotrophs synthesize methanobactin, a secondary metabolite that binds copper
with an unprecedentedly high affinity. Such a strategy may provide methanotrophs
a "copper monopoly" that can inhibit the activity of copper-containing enzymes of
other microbes, e.g., copper-dependent N2O reductases. Here, we show that
methanobactin from Methylosinus trichosporium OB3b inhibited N2O reduction in
denitrifiers. When Pseudomonas stutzeri DCP-Ps1 was incubated in cocultures with
M. trichosporium OB3b or with purified methanobactin from M. trichosporium OB3b,
stoichiometric N2O production was observed from NO3- reduction, whereas no
significant N2O accumulation was observed in cocultures with a mutant defective
in methanobactin production. Copper uptake by P. stutzeri DCP-Ps1 was inhibited
by the presence of purified methanobactin, leading to a significant
downregulation of nosZ transcription. Similar findings were observed with three
other denitrifier strains. These results suggest that in situ stimulation of
methanotrophs can inadvertently increase N2O emissions, with the potential for
increasing net greenhouse gas emissions.
PMID- 29330533
TI - Soil contamination alters the willow root and rhizosphere metatranscriptome and
the root-rhizosphere interactome.
AB - Phytoremediation using willows is thought to be a sustainable alternative to
traditional remediation techniques involving excavation, transport, and
landfilling. However, the complexity of the interaction between the willow and
its associated highly diverse microbial communities makes the optimization of
phytoremediation very difficult. Here, we have sequenced the rhizosphere
metatranscriptome of four willow species and the plant root metatranscriptome for
two willow species growing in petroleum hydrocarbon-contaminated and non
contaminated soils on a former petroleum refinery site. Significant differences
in the abundance of transcripts related to different bacterial and fungal taxa
were observed between willow species, mostly in contaminated soils. When
comparing transcript abundance in contaminated vs. non-contaminated soil for each
willow species individually, transcripts for many microbial taxa and functions
were significantly more abundant in contaminated rhizosphere soil for Salix
eriocephala, S. miyabeana and S. purpurea, in contrast to what was observed in
the rhizosphere of S. caprea. This agrees with the previously reported
sensitivity of S. caprea to contamination, and the superior tolerance of S.
miyabeana and S. purpurea to soil contamination at that site. The root
metatranscriptomes of two species were compared and revealed that plants
transcripts are mainly influenced by willow species, while microbial transcripts
mainly responded to contamination. A comparison of the rhizosphere and root
metatranscriptomes in the S. purpurea species revealed a complete reorganization
of the linkages between root and rhizosphere pathways when comparing willows
growing in contaminated and non-contaminated soils, mainly because of large
shifts in the rhizosphere metatranscriptome.
PMID- 29330534
TI - When increasing population density can promote the evolution of metabolic
cooperation.
AB - Microbial cooperation drives ecological and epidemiological processes and is
affected by the ecology and demography of populations. Population density
influences the selection for cooperation, with spatial structure and the type of
social dilemma, namely public-goods production or self-restraint, shaping the
outcome. While existing theories predict that in spatially structured
environments increasing population density can select either for or against
cooperation, experimental studies with both public-goods production and self
restraint systems have only ever shown that increasing population density favours
cheats. We suggest that the disparity between theory and empirical studies
results from experimental procedures not capturing environmental conditions
predicted by existing theories to influence the outcome. Our study resolves this
issue and provides the first experimental evidence that high population density
can favour cooperation in spatially structured environments for both self
restraint and public-goods production systems. Moreover, using a multi-trait
mathematical model supported by laboratory experiments we extend this result to
systems where the self-restraint and public-goods social dilemmas interact. We
thus provide a systematic understanding of how the strength of interaction
between the two social dilemmas and the degree of spatial structure within an
environment affect selection for cooperation. These findings help to close the
current gap between theory and experiments.
PMID- 29330535
TI - The stoichiometry of coral-dinoflagellate symbiosis: carbon and nitrogen cycles
are balanced in the recycling and double translocation system.
AB - Symbioses between microalgae and animal hosts have the advantage of acquiring and
sharing autotrophically produced organic carbon (C) as their energy source.
However, the stoichiometry and turnover rates of biological elements in symbioses
are not fully understood because of complicated metabolic interactions. We report
the first comprehensive and simultaneous measurement of C and nitrogen (N) flows
through coral-dinoflagellate symbiosis by using the unique approach of dual
isotope labeling with 13C and 15N, in situ chasing, and isotope-mixing models.
The coral autotrophy occurred with much lower C:N ratios than previously thought,
and the autotrophically produced N-rich organic matter was efficiently
transferred to the animal host through two different pathways. In contrast to the
dynamic N cycles within the symbiosis, the N uptake from the ambient seawater was
extremely limited, which enabled the coral symbiosis to sustain N with a long
turnover time (1 year). These findings suggest that coral endosymbionts are not
under N limitation but are actively producing organic N and driving microscale N
cycles in the reef ecosystem. The present techniques could be applied to further
quantify the C and N cycles in other symbiotic interactions and reveal their
ecological advantages.
PMID- 29330537
TI - Tracing the role of human civilization in the globalization of plant pathogens.
PMID- 29330536
TI - Carbon limitation drives GC content evolution of a marine bacterium in an
individual-based genome-scale model.
AB - An important unanswered question in evolutionary genomics is the source of
considerable variation of genomic base composition (GC content) even among
organisms that share one habitat. Evolution toward GC-poor genomes has been
considered a major adaptive pathway in the oligotrophic ocean, but GC-rich
bacteria are also prevalent and highly successful in this environment. We
quantify the contribution of multiple factors to the change of genomic GC content
of Ruegeria pomeroyi DSS-3, a representative and GC-rich member in the globally
abundant Roseobacter clade, using an agent-based model. The model simulates 2 *
108 cells, which allows random genetic drift to act in a realistic manner. Each
cell has a whole genome subject to base-substitution mutation and recombination,
which affect the carbon and nitrogen requirements of DNA and protein pools.
Nonsynonymous changes can be functionally deleterious. Together, these factors
affect the growth and fitness. Simulations show that experimentally determined
mutation bias toward GC is not sufficient to build the GC-rich genome of DSS-3.
While nitrogen availability has been repeatedly hypothesized to drive the
evolution of GC content in marine bacterioplankton, our model instead predicts
that DSS-3 and its ancestors have been evolving in environments primarily limited
by carbon.
PMID- 29330538
TI - Flux of the biogenic volatiles isoprene and dimethyl sulfide from an oligotrophic
lake.
AB - Biogenic volatile organic compounds (BVOCs) affect atmospheric chemistry, climate
and regional air quality in terrestrial and marine atmospheres. Although isoprene
is a major BVOC produced in vascular plants, and marine phototrophs release
dimethyl sulfide (DMS), lakes have been widely ignored for their production. Here
we demonstrate that oligotrophic Lake Constance, a model for north temperate deep
lakes, emits both volatiles to the atmosphere. Depth profiles indicated that
highest concentrations of isoprene and DMS were associated with the chlorophyll
maximum, suggesting that their production is closely linked to phototrophic
processes. Significant correlations of the concentration patterns with taxon
specific fluorescence data, and measurements from algal cultures confirmed the
phototrophic production of isoprene and DMS. Diurnal fluctuations in lake
isoprene suggested an unrecognised physiological role in environmental
acclimation similar to the antioxidant function of isoprene that has been
suggested for marine biota. Flux estimations demonstrated that lakes are a
currently undocumented source of DMS and isoprene to the atmosphere. Lakes may be
of increasing importance for their contribution of isoprene and DMS to the
atmosphere in the arctic zone where lake area coverage is high but terrestrial
sources of BVOCs are small.
PMID- 29330540
TI - Author Correction: REST regulates the cell cycle for cardiac development and
regeneration.
AB - The original version of this Article contained an error in the spelling of the
author Jianyun Yan, which was incorrectly given as Jiangyun Yan. This has now
been corrected in both the PDF and HTML versions of the Article.
PMID- 29330539
TI - Missing Value Imputation Approach for Mass Spectrometry-based Metabolomics Data.
AB - Missing values exist widely in mass-spectrometry (MS) based metabolomics data.
Various methods have been applied for handling missing values, but the selection
can significantly affect following data analyses. Typically, there are three
types of missing values, missing not at random (MNAR), missing at random (MAR),
and missing completely at random (MCAR). Our study comprehensively compared eight
imputation methods (zero, half minimum (HM), mean, median, random forest (RF),
singular value decomposition (SVD), k-nearest neighbors (kNN), and quantile
regression imputation of left-censored data (QRILC)) for different types of
missing values using four metabolomics datasets. Normalized root mean squared
error (NRMSE) and NRMSE-based sum of ranks (SOR) were applied to evaluate
imputation accuracy. Principal component analysis (PCA)/partial least squares
(PLS)-Procrustes analysis were used to evaluate the overall sample distribution.
Student's t-test followed by correlation analysis was conducted to evaluate the
effects on univariate statistics. Our findings demonstrated that RF performed the
best for MCAR/MAR and QRILC was the favored one for left-censored MNAR. Finally,
we proposed a comprehensive strategy and developed a public-accessible web-tool
for the application of missing value imputation in metabolomics (
https://metabolomics.cc.hawaii.edu/software/MetImp/ ).
PMID- 29330541
TI - 19F-perfluorocarbon-labeled human peripheral blood mononuclear cells can be
detected in vivo using clinical MRI parameters in a therapeutic cell setting.
AB - A 19Fluorine (19F) perfluorocarbon cell labeling agent, when employed with an
appropriate cellular MRI protocol, allows for in vivo cell tracking. 19F cellular
MRI can be used to non-invasively assess the location and persistence of cell
based cancer vaccines and other cell-based therapies. This study was designed to
determine the feasibility of labeling and tracking peripheral blood mononuclear
cells (PBMC), a heterogeneous cell population. Under GMP-compliant conditions
human PBMC were labeled with a 19F-based MRI cell-labeling agent in a manner safe
for autologous re-injection. Greater than 99% of PBMC labeled with the 19F cell
labeling agent without affecting functionality or affecting viability. The 19F
labeled PBMC were detected in vivo in a mouse model at the injection site and in
a draining lymph node. A clinical cellular MR protocol was optimized for the
detection of PBMC injected both at the surface of a porcine shank and at a depth
of 1.2 cm, equivalent to depth of a human lymph node, using a dual 1H/19F dual
switchable surface radio frequency coil. This study demonstrates it is feasible
to label and track 19F-labeled PBMC using clinical MRI protocols. Thus, 19F
cellular MRI represents a non-invasive imaging technique suitable to assess the
effectiveness of cell-based cancer vaccines.
PMID- 29330542
TI - Regulation of metabolism in Escherichia coli during growth on mixtures of the non
glucose sugars: arabinose, lactose, and xylose.
AB - Catabolite repression refers to the process where the metabolism of one sugar
represses the genes involved in metabolizing another sugar. While glucose
provides the canonical example, many other sugars are also known to induce
catabolite repression. However, less is known about the mechanism for catabolite
repression by these non-glucose sugars. In this work, we investigated the
mechanism of catabolite repression in the bacterium Escherichia coli during
growth on lactose, L-arabinose, and D-xylose. The metabolism of these sugars is
regulated in a hierarchical manner, where lactose is the preferred sugar,
followed by L-arabinose, and then D-xylose. Previously, the preferential
utilization of L-arabinose over D-xylose was found to result from transcriptional
crosstalk. However, others have proposed that cAMP governs the hierarchical
regulation of many non-glucose sugars. We investigated whether lactose-induced
repression of L-arabinose and D-xylose gene expression is due to transcriptional
crosstalk or cAMP. Our results demonstrate that it is due to cAMP and not
transcriptional crosstalk. In addition, we found that repression is reciprocal,
where both L-arabinose and D-xylose also repress the lactose gene expression,
albeit to a lesser extent and also through a mechanism involving cAMP.
Collectively, the results further our understanding of metabolism during growth
on multiple sugars.
PMID- 29330544
TI - Perceptions of legislation relating to the sharing of genomic biobank results
with donors-a survey of BBMRI-ERIC biobanks.
AB - Biobanks accumulate huge amounts of research findings, including participants'
genomic data. Increasingly this leads to biobanks receiving research results that
could be of clinical significance to biobank participants. The EU Horizon 2020
Project 'Genetics Clinic of the Future' surveyed European biobanks' perceptions
of the legal and regulatory requirements for communicating individual research
results to donors. The goal was to gain background knowledge for possible future
guidelines, especially relating to the consent process. The Survey was
implemented using a web-based Webropol tool. The questionnaire was sent at the
end of 2015 to 351 European biobanks in 13 countries that are members of BBMRI
ERIC (Biobanking and Biomolecular Resources Research Infrastructure-European
Research Infrastructure Consortium). Seventy-two biobanks responded to the
survey, representing each of the 13 BBMRI Member States. Respondents were mainly
individuals responsible for the governance of biobanks. The replies indicate that
the majority of the respondents thought that their national legislation allowed
them to contact participants to communicate results, and that research
participants had the right to request their results. However, respondents'
understanding of their national legislation varied even within member states. Our
results indicate that legislation applied to biobanks in many countries may be
scattered and difficult to interpret. In BBMRI-ERIC, there is an ongoing
discussion about the need for European recommendations on sharing genomic biobank
results with donors, which may pave the way for more coherent global guidelines.
Our results form a basis for this work.
PMID- 29330543
TI - CUGC for Duchenne muscular dystrophy (DMD).
PMID- 29330545
TI - De novo BK channel variant causes epilepsy by affecting voltage gating but not
Ca2+ sensitivity.
AB - Epilepsy is one of the most common neurological diseases and it causes profound
morbidity and mortality. We identified the first de novo variant in KCNMA1
(c.2984 A > G (p.(N995S)))-encoding the BK channel-that causes epilepsy, but not
paroxysmal dyskinesia, in two independent families. The c.2984 A > G (p.(N995S))
variant markedly increased the macroscopic potassium current by increasing both
the channel open probability and channel open dwell time. The c.2984 A > G
(p.(N995S)) variant did not affect the calcium sensitivity of the channel. We
also identified three other variants of unknown significance (c.1554 G > T
(p.(K518N)), c.1967A > C (p.(E656A)), and c.3476 A > G (p.(N1159S))) in three
separate patients with divergent epileptic phenotypes. However, these variants
did not affect the BK potassium current, and are therefore unlikely to be disease
causing. These results demonstrate that BK channel variants can cause epilepsy
without paroxysmal dyskinesia. The underlying molecular mechanism can be
increased activation of the BK channel by increased sensitivity to the voltage
dependent activation without affecting the sensitivity to the calcium-dependent
activation. Our data suggest that the BK channel may represent a drug target for
the treatment of epilepsy. Our data highlight the importance of functional
electrophysiological studies of BK channel variants in distinguishing whether a
genomic variant of unknown significance is a disease-causing variant or a benign
variant.
PMID- 29330546
TI - Older mothers and increased impact of prenatal screening: stable livebirth
prevalence of trisomy 21 in the Netherlands for the period 2000-2013.
AB - In the Netherlands, there is no registry system regarding the livebirth
prevalence of trisomy 21 (T21). In 2007, a national screening programme was
introduced for all pregnant women, which may have changed the livebirth
prevalence of T21. The aim of this study is to analyse trends in factors that
influence livebirth prevalence of T21 and to estimate the livebirth prevalence of
T21 for the period of 2000-2013. National data sets were used on the following:
(1) livebirths according to maternal age and (2) prenatal testing and termination
of pregnancy (ToP) following diagnosis of T21. These data are combined in a model
that uses maternal age-specific risk on T21 and correction factors for natural
foetal loss to assess livebirth prevalence of T21. The proportion of mothers aged
>= 36 years has increased from 12.2% in 2000 to 16.6% in 2009, to gradually
decrease afterwards to 15.2% in 2013. The number of invasive tests performed
adjusted for total livebirths decreased (5.9% in 2000 vs. 3.2% in 2013) with
0.18% a year (95% CI: -0.21 to -0.15; p < 0.001). Following invasive testing, a
higher proportion of foetuses was diagnosed with T21 (1.6% in 2000 vs. 4.8% in
2013) with a significant increase of 0.22% a year (95% CI: 0.18-0.26; p < 0.001).
The proportion of ToP subsequent to T21 diagnosis was on average 85.7%, with no
clear time trend. This resulted in a stable T21 livebirth prevalence of 13.6 per
10,000 livebirths (regression coefficient -0.025 (95% CI: -0.126 to 0.77; p =
0.60).
PMID- 29330547
TI - Recessive loss of function PIGN alleles, including an intragenic deletion with
founder effect in La Reunion Island, in patients with Fryns syndrome.
AB - Fryns syndrome (FS) is a multiple malformations syndrome with major features of
congenital diaphragmatic hernia, pulmonary hypoplasia, craniofacial dysmorphic
features, distal digit hypoplasia, and a range of other lower frequency
malformations. FS is typically lethal in the fetal or neonatal period.
Inheritance is presumed autosomal recessive. Although no major genetic cause has
been identified for FS, biallelic truncating variants in PIGN, encoding a
component of the glycosylphosphatidylinositol (GPI)-anchor biosynthesis pathway,
have been identified in a limited number of cases with a phenotype compatible
with FS. Biallelic variants in PIGN, typically missense or compound missense with
truncating, also cause multiple congenital anomalies-hypotonia-seizures syndrome
1 (MCAHS1). Here we report six further patients with FS with or without
congenital diaphragmatic hernia and recessive loss of function PIGN alleles,
including an intragenic deletion with a likely founder effect in La Reunion and
other Indian Ocean islands. Our results support the hypothesis that a spectrum of
phenotypic severity is associated with recessive PIGN variants, ranging from FS
at the extreme end, caused by complete loss of function, to MCAHS1, in which some
residual PIGN function may remain. Our data add FS resulting from PIGN variants
to the catalog of inherited GPI deficiencies caused by the disruption of the GPI
anchor biosynthesis pathway.
PMID- 29330549
TI - Excellent room temperature deformability in high strain rate regimes of magnesium
alloy.
AB - Magnesium and its alloys have the lowest density among structural metallic
materials; thus, this light-weight metal has great potential for reducing the
weight, for example, of vehicles and trains. However, due to its crystal
structure, deformability is poor; in particular, under compressive stress. In
this study, we modified magnesium with bismuth as an alloying element, which has
the characteristics of being likely to form precipitates instead of grain
boundary segregation. The Mg-Bi binary alloy showed excellent deformability and
high absorption of energy in high-strain rate regimes at room temperature via
contribution of grain boundary sliding. These properties, which are closely
comparable to those of conventional middle-strength aluminum alloys (Al-Mg and Al
Mg-Si series alloys), have never been observed before in magnesium alloys. The
development of such properties opens the door for not only academic but also
industrial research in magnesium.
PMID- 29330548
TI - SHOX haploinsufficiency presenting with isolated short long bones in the second
and third trimester.
AB - Haploinsufficiency of the transcription factor short stature homeobox (SHOX)
manifests as a spectrum of clinical phenotypes, ranging from disproportionate
short stature and Madelung deformity to isolated short stature. Here, we describe
five infants with molecularly confirmed diagnoses of SHOX haploinsufficiency who
presented in utero with short long bones during routine antenatal scanning from
as early as 19 weeks gestation. Other foetal growth parameters were normal. The
molecular basis of SHOX haploinsufficiency was distinct in each case. In four
cases, SHOX haploinsufficiency was inherited from a previously undiagnosed
parent. In our de novo case, SHOX haploinsufficiency reflected the formation of a
derivative sex chromosome during paternal meiosis. Final adult height in the SHOX
deficient parents ranged from -1.9 to -1.2 SDS. All affected parents had
disproportionately short limbs and two affected mothers had bilateral Madelung
deformity. To our knowledge, SHOX haploinsufficiency has not previously been
reported to present in utero. Our experience illustrates that SHOX deficiency
should form part of the differential diagnosis of foetal short long bones and
suggests a low threshold for genetic testing. This should be particularly
targeted at, but not limited to, families with a history of features suggestive
of SHOX deficiency. Data on the postnatal growth of our index cases is presented
which demonstrates that antenatal presentation of SHOX haploinsufficiency is not
indicative of severe postnatal growth restriction. Early identification of SHOX
deficiency will enable accurate genetic counselling reflecting a good postnatal
outcome and facilitate optimal initiation of growth hormone therapy.
PMID- 29330553
TI - Remote Microphone System Use at Home: Impact on Caregiver Talk.
AB - Purpose: The purpose of this study was to investigate the effects of home use of
a remote microphone system (RMS) on the spoken language production of caregivers
with young children who have hearing loss. Method: Language Environment Analysis
recorders were used with 10 families during 2 consecutive weekends (RMS weekend
and No-RMS weekend). The amount of talk from a single caregiver that could be
made accessible to children with hearing loss when using an RMS was estimated
using Language Environment Analysis software. The total amount of caregiver talk
(close and far talk) was also compared across both weekends. In addition,
caregivers' perceptions of RMS use were gathered. Results: Children, with the use
of RMSs, could potentially have access to approximately 42% more words per day.
In addition, although caregivers produced an equivalent number of words on both
weekends, they tended to talk more from a distance when using the RMS than when
not. Finally, caregivers reported positive perceived communication benefits of
RMS use. Conclusions: Findings from this investigation suggest that children with
hearing loss have increased access to caregiver talk when using an RMS in the
home environment. Clinical implications and future directions for research are
discussed.
PMID- 29330551
TI - Autapses promote synchronization in neuronal networks.
AB - Neurological disorders such as epileptic seizures are believed to be caused by
neuronal synchrony. However, to ascertain the causal role of neuronal
synchronization in such diseases through the traditional approach of
electrophysiological data analysis remains a controversial, challenging, and
outstanding problem. We offer an alternative principle to assess the
physiological role of neuronal synchrony based on identifying structural
anomalies in the underlying network and studying their impacts on the collective
dynamics. In particular, we focus on autapses - time delayed self-feedback links
that exist on a small fraction of neurons in the network, and investigate their
impacts on network synchronization through a detailed stability analysis. Our
main finding is that the proper placement of a small number of autapses in the
network can promote synchronization significantly, providing the computational
and theoretical bases for hypothesizing a high degree of synchrony in real
neuronal networks with autapses. Our result that autapses, the shortest possible
links in any network, can effectively modulate the collective dynamics provides
also a viable strategy for optimal control of complex network dynamics at minimal
cost.
PMID- 29330552
TI - Dosimetry Prediction for Clinical Translation of 64Cu-Pembrolizumab ImmunoPET
Targeting Human PD-1 Expression.
AB - The immune checkpoint programmed death 1 receptor (PD-1) expressed on some tumor
infiltrating lymphocytes, and its ligand (PD-L1) expressed on tumor cells, enable
cancers to evade the immune system. Blocking PD-1 with the monoclonal antibody
pembrolizumab is a promising immunotherapy strategy. Thus, noninvasively
quantifying the presence of PD-1 expression in the tumor microenvironment prior
to initiation of immune checkpoint blockade may identify the patients likely to
respond to therapy. We have developed a 64Cu-pembrolizumab radiotracer and
evaluated human dosimetry. The tracer was utilized to image hPD-1 levels in two
subcutaneous mouse models: (a) 293 T/hPD-1 cells xenografted into NOD-scid IL
2Rgammanull mice (NSG/293 T/hPD-1) and (b) human peripheral blood mononuclear
cells engrafted into NSG bearing A375 human melanoma tumors (hNSG/A375). In each
mouse model two cohorts were evaluated (hPD-1 blockade with pembrolizumab [blk]
and non-blocked [nblk]), for a total of four groups (n = 3-5/group). The
xenograft-to-muscle ratio in the NSG/293 T/hPD-1 model at 24 h was significantly
increased in the nblk group (7.0 +/- 0.5) compared to the blk group (3.4 +/-
0.9), p = 0.01. The radiotracer dosimetry evaluation (PET/CT ROI-based and ex
vivo) in the hNSG/A375 model revealed the highest radiation burden to the liver.
In summary, we validated the 64Cu-pembrolizumab tracer's specific hPD-1 receptor
targeting and predicted human dosimetry.
PMID- 29330550
TI - A Metabolomics Pilot Study on Desmoid Tumors and Novel Drug Candidates.
AB - Desmoid tumors (aggressive fibromatosis) are locally invasive soft tissue tumors
that lack the ability to metastasize. There are no directed therapies or standard
treatment plan, and chemotherapeutics, radiation, and surgery often have
temporary effects. The majority of desmoid tumors are related to T41A and S45F
mutations of the beta-catenin encoding gene (CTNNB1). Using broad spectrum
metabolomics, differences were investigated between paired normal fibroblast and
desmoid tumor cells from affected patients. There were differences identified,
also, in the metabolomics profiles associated with the two beta-catenin
mutations, T41A and S45F. Ongoing drug screening has identified currently
available compounds which inhibited desmoid tumor cellular growth by more than
50% but did not affect normal fibroblast proliferation. Two drugs were
investigated in this study, and Dasatinib and FAK Inhibitor 14 treatments
resulted in unique metabolomics profiles for the normal fibroblast and desmoid
tumor cells, in addition to the T41A and S45F. The biochemical pathways that
differentiated the cell lines were aminoacyl-tRNA biosynthesis in mitochondria
and cytoplasm and signal transduction amino acid-dependent mTORC1 activation.
This study provides preliminary understanding of the metabolic differences of
paired normal and desmoid tumors cells, their response to desmoid tumor
therapeutics, and new pathways to target for therapy.
PMID- 29330554
TI - Accuracy of a Screening Tool for Early Identification of Language Impairment.
AB - Purpose: A screening tool called the VTO Language Screening Instrument (VTO-LSI)
was developed to enable more uniform and earlier detection of language
impairment. This report, consisting of 2 retrospective studies, focuses on the
effects of using the VTO-LSI compared to regular detection procedures. Method:
Study 1 retrospectively compared VTO-LSI with regular detection procedures.
Outcome measure was the detection rate of language impairment among 24-month-old
children. Data were retrieved from medical records of children attending a youth
health care center. Study 2 retrospectively compared the effects of VTO-LSI and
regular detection procedures on the age at referral for diagnostic investigations
and the influence of sex. Data were retrieved from medical records from the
speech and hearing center and analyzed with multivariate analysis of variance.
Results: With the VTO-LSI, significantly more cases with language impairment were
identified compared with the regular detection procedure (2.4% vs. 0.4%). In
regions where the VTO-LSI was used, girls were almost 2 years younger, and boys
were 1 year younger when referred to diagnostic investigations than in regions
with regular detection procedures. Conclusion: The VTO-LSI was more effective
than regular detection procedures.
PMID- 29330555
TI - Performance of Low-Income Dual Language Learners Attending English-Only Schools
on the Clinical Evaluation of Language Fundamentals-Fourth Edition, Spanish.
AB - Purpose: The aim of this study was to examine the performance of a group of
Spanish-speaking, dual language learners (DLLs) who were attending English-only
schools and came from low-income and low-parental education backgrounds on the
Clinical Evaluation of Language Fundamentals-Fourth Edition, Spanish (CELF-4S;
Semel, Wiig, & Secord, 2006). Method: Spanish-speaking DLLs (N = 656), ages 5;0
(years;months) to 7;11, were tested for language impairment (LI) using the core
language score of the CELF-4S and the English Structured Photographic Expressive
Language Test (Dawson, Stout, & Eyer, 2003). A subsample (n = 299) was
additionally tested using a Spanish language sample analysis and a newly
developed Spanish morphosyntactic measure, for identification of children with LI
and to conduct a receiver operating characteristics curve analysis. Results: Over
50% of the sample scored more than 1 SD below the mean on the core language
score. In our subsample, the sensitivity of the CELF-4S was 94%, and specificity
was 65%, using a cutoff score of 85 as suggested in the manual. Using an
empirically derived cutoff score of 78, the sensitivity was 86%, and the
specificity was 80%. Conclusions: Results suggest that the CELF-4S overidentifies
low-income Spanish-English DLLs attending English-only schools as presenting with
LI. For this sample, 1 in every 3 Latino children from low socioeconomic status
was incorrectly identified with LI. Clinicians should be cautious when using the
CELF-4S to evaluate low-income Spanish-English DLLs and ensure that they have
converging evidence before making diagnostic decisions.
PMID- 29330556
TI - Evolution of the Phosphatidylcholine Biosynthesis Pathways in Green Algae:
Combinatorial Diversity of Methyltransferases.
AB - Phosphatidylcholine (PC) is one of the most common phospholipids in eukaryotes,
although some green algae such as Chlamydomonas reinhardtii are known to lack PC.
Recently, we detected PC in four species in the genus Chlamydomonas: C. applanata
NIES-2202, C. asymmetrica NIES-2207, C. debaryana NIES-2212, and C. sphaeroides
NIES-2242. To reveal the PC biosynthesis pathways in green algae and the
evolutionary scenario involved in their diversity, we analyzed the PC
biosynthesis genes in these four algae using draft genome sequences. Homology
searches suggested that PC in these species is synthesized by phosphoethanolamine
N-methyltransferase (PEAMT) and/or phosphatidylethanolamine-N-methyltransferase
(PEMT), both of which are absent in C. reinhardtii. Recombinant PEAMTs from these
algae showed methyltransferase activity for phosphoethanolamine but not for
monomethyl phosphoethanolamine in vitro, in contrast to land plant PEAMT, which
catalyzes the three methylations from phosphoethanolamine to phosphocholine. This
suggested an involvement of other methyltransferases in PC biosynthesis. Here, we
characterized the putative phospholipid-N-methyltransferase (PLMT) genes of these
species by genetic and phylogenetic analysis. Complementation assays using a PC
biosynthesis-deficient yeast suggested that the PLMTs of these algae can
synthesize PC from phosphatidylethanolamine. These results indicated that the PC
biosynthesis pathways in green algae differ from those of land plants, although
the enzymes involved are homologous. Phylogenetic analysis suggested that the
PEAMTs and PLMTs in these algae were inherited from the common ancestor of green
algae. The absence of PC biosynthesis in many Chlamydomonas species is likely a
result of parallel losses of PEAMT and PLMT in this genus.
PMID- 29330557
TI - Linear doggybone DNA vaccine induces similar immunological responses to
conventional plasmid DNA independently of immune recognition by TLR9 in a pre
clinical model.
AB - Vaccination with DNA that encodes cancer antigens is a simple and convenient way
to raise immunity against cancer and has already shown promise in the clinical
setting. Conventional plasmid DNA is commonly used which together with the
encoded antigen also includes bacterial immunostimulatory CpG motifs to target
the DNA sensor Toll-like receptor 9. Recently DNA vaccines using doggybone DNA
(dbDNATM), have been developed without the use of bacteria. The cell-free process
relies on the use of Phi29 DNA polymerase to amplify the template followed by
protelomerase TelN to complete individual closed linear DNA. The resulting DNA
contains the required antigenic sequence, a promoter and a poly A tail but lacks
bacterial sequences such as an antibiotic resistance gene, prompting the question
of immunogenicity. Here we compared the ability of doggybone DNA vaccine with
plasmid DNA vaccine to induce adaptive immunity using clinically relevant
oncotargets E6 and E7 from HPV. We demonstrate that despite the inability to
trigger TLR9, doggybone DNA was able to induce similar levels of cellular and
humoral immunity as plasmid DNA, with suppression of established TC-1 tumours.
PMID- 29330558
TI - Variant of a persistent hypoglossal artery supplying only the posterior inferior
cerebellar artery diagnosed by magnetic resonance angiography: a case report.
AB - Very rarely, a persistent hypoglossal artery supplies only the posterior inferior
cerebellar artery without connection to the basilar artery. Few cases diagnosed
by catheter angiography have been reported. We diagnosed a case using magnetic
resonance angiography.
PMID- 29330559
TI - A post-translational balancing act: the good and the bad of SUMOylation in
pancreatic islets.
AB - Post-translational modification of proteins contributes to the control of cell
function and survival. The balance of these in insulin-producing pancreatic beta
cells is important for the maintenance of glucose homeostasis. Protection from
the damaging effects of reactive oxygen species is required for beta cell
survival, but if this happens at the expense of insulin secretory function then
the ability of islets to respond to changing metabolic conditions may be
compromised. In this issue of Diabetologia, He et al (
https://doi.org/10.1007/s00125-017-4523-9 ) show that post-translational
attachment of small ubiquitin-like modifier (SUMO) to target lysine residues
(SUMOylation) strikes an important balance between the protection of beta cells
from oxidative stress and the maintenance of insulin secretory function. They
show that SUMOylation is required to stabilise nuclear factor erythroid 2-related
factor 2 (NRF2) and increase antioxidant gene expression. Decreasing SUMOylation
in beta cells impairs their antioxidant capacity, causes cell death,
hyperglycaemia, and increased sensitivity to streptozotocin-induced diabetes,
while increasing SUMOylation is protective. However, this protection from overt
diabetes occurs in concert with glucose intolerance due to impaired beta cell
function. A possible role for SUMOylation as a key factor balancing beta cell
protection vs beta cell responsiveness to metabolic cues is discussed in this
Commentary.
PMID- 29330562
TI - Influence of genetic polymorphisms of IL23R, STAT3, IL12B, and STAT4 on the risk
of aplastic anemia and the effect of immunosuppressive therapy.
AB - Studies have suggested that IL-23/STAT3 and IL-12/STAT4 signaling pathways
associate with aplastic anemia (AA) occurrence. Polymorphisms in pathway-related
genes may contribute to AA risk. In the current study, we investigated the
association between polymorphisms in genes of IL23R, STAT3, IL12B, and STAT4 and
occurrence, severity, and immunosuppressive outcome of AA in the Han population
in southwest China. In the current 164 AA cases and 211 controls study, we found
T allele and TT genotype of rs7574865 were more frequent in the cases than that
in the controls. In the additive model, individual carrying rs7574865 T allele
demonstrated a 37% (OR (95% CI) = 1.37 (1.02-1.85), Pper = 0.036) increased AA
risk. In the recessive model, carrier with rs7574865 TT genotype showed a 2.08
fold increased AA risk (OR (95% CI) = 2.08 (1.14-3.70), Pper = 0.017).
Additionally, we showed that G allele and GG genotype of rs11209032 were more
frequent in the 88 non-severe AA cases than that in the 76 severe AA ones. Our
study also found G allele and GG genotype of rs11209032, and GG-genotype of
rs744166 associated with the immunosuppressive therapy outcome in AA patients.
Current study results support that functional STAT4 (rs7574865), IL23R
(rs11209032), and STAT3 (rs744166) variants may associate with occurrence,
severity, and immunosuppressive outcome of AA in the Han population in southwest
China.
PMID- 29330563
TI - Serious concerns on the inability of FDG-PET in excluding residual viable
lymphoma.
PMID- 29330560
TI - Altered Bone Remodeling in Psoriatic Disease: New Insights and Future Directions.
AB - Psoriatic arthritis (PsA) is an inflammatory rheumatic disorder that occurs in
patients with psoriasis and predominantly affects musculoskeletal structures,
skin, and nails. The etiology of PsA is not well understood but evidence supports
an interplay of genetic, immunologic, and environmental factors which promote
pathological bone remodeling and joint damage in PsA. Localized and systemic bone
loss due to increased activity of osteoclasts is well established in PsA based on
animal models and translational studies. In contrast, the mechanisms responsible
for pathological bone remodeling in PsA remain enigmatic although new candidate
molecules and pathways have been identified. Recent reports have revealed novel
findings related to bone erosion and pathologic bone formation in PsA. Many
associated risk factors and contributing molecular mechanisms have also been
identified. In this review, we discuss new developments in the field, point out
unresolved questions regarding the pathogenetic origins of the wide array of bone
phenotypes in PsA, and discuss new directions for investigation.
PMID- 29330561
TI - Salvage therapy post pomalidomide-based regimen in relapsed/refractory myeloma.
AB - The combination of pomalidomide and low-dose dexamethasone (Pom-Dex) has proved
effective and safe in patients with end-stage relapsed/refractory multiple
myeloma (RRMM), otherwise characterized by a very poor outcome. MM remains an
incurable disease with unavoidable relapses, and the outcome after pomalidomide
is still dismal. However, some patients demonstrate prolonged survival even
beyond pomalidomide therapy.We sought to analyze the treatment of RRMM patients
following Pom-Dex therapy and the response and survival after this next treatment
line.We studied 134 patients treated with Pom-Dex until progression across two
IFM studies. Seventy percent of these patients received further therapy after Pom
Dex. Among the treated patients, one third responded and one third maintained
stable disease. The median OS for treated patients was 12 months (6.5;17), with
22 and 12.5% of patients surviving beyond 2 and 3 years, respectively. The
factors associated with a better outcome were exposure to a triplet-based regimen
containing a novel agent, response to therapy, absence of adverse cytogenetic,
and a longer time from diagnosis to post pomalidomide therapy.This study suggests
that patients relapsing after Pom-Dex therapy can still benefit from a further
line of treatment. A subset of these treated patients even displayed a prolonged
OS, while the prognosis remained very poor without treatment. An active approach
could therefore be recommended even in this adverse situation, however guided by
the patients' prognosis factors.
PMID- 29330571
TI - Impact of motor task execution on an individual's ability to mirror forearm
positions.
AB - This work is motivated by our goal of determining why individuals with stroke are
impaired when locating their arms in space. We assessed the ability of
individuals without neurological impairments to mirror their forearms during
various motor tasks so that we could identify baseline performance in an
unimpaired population. Nine right-hand dominant participants without neurological
impairments mirrored forearm positions bi-directionally (i.e., right forearm
mirrors left forearm, vice versa) for three motor tasks (i.e., passive,
passive/active, and active) and two position identification modes (i.e.,
mirroring to a position stored in working memory versus concurrently felt by the
opposite arm). During each trial, the participant's reference forearm moved to a
flexion ([Formula: see text]) or extension ([Formula: see text]) position, and
then, their opposite forearm mirrored the position of their reference forearm.
The main finding across all tested conditions is that participants mirrored
forearm positions with an average magnitude of error [Formula: see text]. When
controlling their forearms' movements (active motor task), participants mirrored
forearm positions more accurately by up to, on average, [Formula: see text] at
the flexion location than at the extension location. Moreover, participants
mirrored forearm positions more accurately by up to, on average, [Formula: see
text] when their forearms were moved for them rather than when they controlled
their forearms' movements. Task directionality and position identification mode
did not significantly affect participant arm mirroring accuracy. These findings
are relevant for interpreting in future work the reason why impairments occur, on
similar tasks, in individuals with altered motor commands, working memory, and
arm impedance, e.g., post-stroke hemiparesis.
PMID- 29330570
TI - Open-door laminoplasty : What can the unilateral approach offer?
AB - OBJECTIVE: Multilevel posterior decompression of subaxial cervical spinal canal
stenosis through a less-invasive unilateral approach. INDICATIONS: Degenerative
cervical myelopathy due to multilevel subaxial spinal canal stenosis.
CONTRAINDICATIONS: Cervical kyphosis or instability, bilateral radiculopathy due
to foraminal stenosis, involvement of C2 or C7. SURGICAL TECHNIQUE: Unilateral
subaxial approach with detachment of muscles only on one side. The ipsilateral
laminae C6 to C3 are cut at the laminofacet junction and opened up. The loss of
resistance is usually due to a greenstick fracture in the proximity of the
contralateral laminofacet junction. The opened laminae are fixed with Z-shaped
thin titanium plates. If necessary, the laminoplasty can be combined with a
unilateral fixation and fusion by the same approach. POSTOPERATIVE MANAGEMENT:
Early mobilization 4-6 h postoperatively. No orthosis necessary. RESULTS: A total
of 131 patients (77 men, mean age 67 years) with a multilevel cervical
spondylotic myelopathy (CSM) underwent surgery using a posterior approach. In 52
patients (40%), a unilateral approach was performed (laminoplasty: n = 30;
laminoplasty/fusion: n = 22). In this group, the mean operation time was less
compared with two other techniques (unilateral approach: 110 min;
laminectomy/fusion: 150 min; 360 degrees approach: 210 min). The postoperative
European myelopathy score (EMS) improved from 12.8 to 15.2. The overall
complication rate was 17% (unilateral approach: 9%; laminectomy/fusion: 18%; 360
degrees approach: 27%).
PMID- 29330572
TI - Effects of whole-body vibration on muscle strength, bone mineral content and
density, and balance and body composition of children and adolescents with Down
syndrome: a systematic review.
AB - The aim of this study is to verify the effects of whole-body vibration (WBV)
training on the muscle strength of children and adolescents with Down syndrome.
We searched MEDLINE, Cochrane, SciELO, Lilacs and PUBMED databases and included
manual searches to identify randomised controlled trials to investigate the
effects of WBV on the structure and body function of children and adolescents
with Down syndrome. Two reviewers independently selected the studies and
performed statistical analysis. In total, five studies with 171 patients that
compared WBV with exercise and/or control were included. Two studies demonstrated
a significant difference between the muscle strength of children and adolescents
with Down syndrome who received WBV training and that of those who did not
receive the intervention. The studies included in this systematic review showed
that WBV training has positive effects on bone mineral density (BMD), body
composition and balance. Results of this study showed that WBV training improves
muscle strength, BMD, body composition and balance of children and adolescents
with Down syndrome, and a more in-depth analysis of its effects on other
variables in this population is required, as well as of parameters to be used.
PMID- 29330573
TI - Tocotrienol supplementation suppressed bone resorption and oxidative stress in
postmenopausal osteopenic women: a 12-week randomized double-blinded placebo
controlled trial.
AB - : Tocotrienols have shown bone-protective effect in animals. This study showed
that a 12-week tocotrienol supplementation decreased concentrations of bone
resorption biomarker and bone remodeling regulators via suppressing oxidative
stress in postmenopausal osteopenic women. INTRODUCTION: Tocotrienols (TT) have
been shown to benefit bone health in ovariectomized animals, a model of
postmenopausal women. The purpose of this study was to evaluate the effect of 12
week TT supplementation on bone markers (serum bone-specific alkaline phosphatase
(BALP), urine N-terminal telopeptide (NTX), serum soluble receptor activator of
nuclear factor-kappaB ligand (sRANKL), and serum osteoprotegerin (OPG)), urine
calcium, and an oxidative stress biomarker (8-hydroxy-2'-deoxyguanosine (8-OHdG))
in postmenopausal women with osteopenia. METHODS: Eighty-nine postmenopausal
osteopenic women (59.7 +/- 6.8 year, BMI 28.7 +/- 5.7 kg/m2) were randomly
assigned to three groups: (1) placebo (430 mg olive oil/day), (2) low TT (430 mg
TT/day, 70% purity), and (3) high TT (860 mg TT/day, 70% purity). TT, an extract
from annatto seed with 70% purity, consisted of 90% delta-TT and 10% gamma-TT.
Overnight fasting blood and urine samples were collected at baseline, 6, and 12
weeks for biomarker analyses. Eighty-seven subjects completed the 12-week study.
RESULTS: Relative to the placebo group, there were marginal decreases in serum
BALP level in the TT-supplemented groups over the 12-week study period.
Significant decreases in urine NTX levels, serum sRANKL, sRANKL/OPG ratio, and
urine 8-OHdG concentrations and a significant increase in BALP/NTX ratio due to
TT supplementation were observed. TT supplementation did not affect serum OPG
concentrations or urine calcium levels throughout the study period. There were no
significant differences in NTX level, BALP/NTX ratio, sRANKL level, and
sRANKL/OPG ratio between low TT and high TT groups. CONCLUSIONS: Twelve-week
annatto-extracted TT supplementation decreased bone resorption and improved bone
turnover rate via suppressing bone remodeling regulators in postmenopausal women
with osteopenia. Such osteoprotective TT's effects may be, in part, mediated by
an inhibition of oxidative stress. TRIAL REGISTRATION: ClinicalTrials.gov
identifier: NCT02058420. TITLE: Tocotrienols and bone health of postmenopausal
women.
PMID- 29330574
TI - Ectomycorrhizal fungal communities in alpine relict forests of Pinus pumila on
Mt. Norikura, Japan.
AB - Ectomycorrhizal (ECM) symbioses are indispensable for the establishment of host
trees, yet available information of ECM symbiosis in alpine forests is scarce.
Pinus pumila is a typical ice age relict tree species in Japan and often forms
monodominant dwarf vegetation above the tree line in mountains. We studied ECM
fungi colonizing P. pumila on Mt. Norikura, Japan, with reference to host
developmental stages, i.e., from current-year seedlings to mature trees. ECM
fungal species were identified based on rDNA ITS sequences. Ninety-two ECM fungal
species were confirmed from a total of 2480 root tips examined. Species in
/suillus-rhizopogon and /wilcoxina were dominant in seedling roots. ECM fungal
diversity increased with host development, due to the addition of species-rich
fungal lineages (/cenococcum, /cortinarius, and /russula-lactarius) in late
successional stages. Such successional pattern of ECM fungi is similar to those
in temperate pine systems, suggesting the predominant role of /suillus-rhizopogon
in seedling establishment, even in relict alpine habitats fragmented and isolated
for a geological time period. Most of the ECM fungi detected were also recorded
in Europe or North America, indicating their potential Holarctic distribution and
the possibility of their comigration with P. pumila through land bridges during
ice ages. In addition, we found significant effects of soil properties on ECM
fungal communities, which explained 34.1% of the total variation of the fungal
communities. While alpine vegetation is regarded as vulnerable to the ongoing
global warming, ECM fungal communities associated with P. pumila could be altered
by the edaphic change induced by the warming.
PMID- 29330575
TI - A new technique for minimal invasive complete spinal cord injury in minipigs.
AB - BACKGROUND: The aim of this study was to develop a minimal invasive complete
spinal cord injury (SCI) minipig model for future research applications. The
minipig is considered a translationally relevant model for SCI research. However,
a standardized minimal invasive complete SCI model for pigs has not yet been
established. METHODS: Adult Gottingen minipigs were anesthetized and placed in
extended prone position. After initial computed tomography (CT) scan, the skin
was incised, a needle placed in the epidural fatty tissue. Using the Seldinger
technique, a guidewire and dilators were introduced to insert the balloon
catheter to Th12. After confirmation of the level Th11/Th12, the balloon was
inflated to 2 atm for 30 min. The severity of the lesion was followed by CT and
by MRI, and by immunohistochemistry. Function was assessed at the motor and
sensory level. RESULTS: Duration of procedure was about 60 min including the 30
min compression time. The balloon pressure of 2 atm was maintained without
losses. The lesion site was clearly discernible and no intradural bleeding was
observed by CT. Neurological assessments during the 4-month follow-up time showed
consistent, predictable, and stable neurological deficits. Magnetic resonance
imaging analyses at 6 h and 4 weeks post SCI with final immunohistochemical
analyses of spinal cord tissue underlined the neurological outcomes and proved
SCI completeness. CONCLUSIONS: We have established a new, minimal invasive,
highly standardized, CT-guided spinal cord injury procedure for minipigs. All
risks of the open surgery can be excluded using this technique. This CT-guided SC
compression is an excellent technique as it avoids long surgery and extensive
trauma and allows a feasible inter-animal comparison.
PMID- 29330576
TI - Xipho-pubic angle (XPA) correlates with patient's reported outcomes in a
population of adult spinal deformity: results from a multi-center cohort study.
AB - STUDY DESIGN: Retrospective multi-center cohort study. PURPOSE: Sagittal
misalignment causes changes in the abdominal shape. Xipho-pubic angle (XPA) has
been previously described to radiographically evaluate the shape of the abdominal
cavity in patients with spine deformity. The aims of this study are to evaluate
the correlation of XPA-to-spinopelvic sagittal parameters and to patients' health
related quality-of-life (HRQoL) scores. METHODS: 278 patients from a multi-center
database with diagnosis adult spinal deformity (ASD) (one or more of: coronal
Cobb angle > 20 degrees , sagittal vertical axis (SVA) > 50 mm, pelvic tilt (PT)
> 25 degrees , and thoracic kyphosis > 60 degrees ) were included. Cut-off values
for moderate and severe disability (ODI-Oswestry Disability Index-20 and 40%)
were calculated. Pearson's correlation was tested between XPA and spinopelvic
parameters and between XPA and HRQoL scores. RESULTS: The cut-off value of XPA to
identify ODI severe disability (40/100) was identified with XPA smaller than 103
degrees ; minimal (20/100) disability was identified by XPA greater than 113
degrees . XPA showed strong correlation to sagittal spinopelvic parameters-PT,
SVA, lumbar lordosis (LL), pelvic incidence (PI) minus LL-and to HRQoL scores
ODI, SF-36 PCS and SRS-22 activity and pain. XPA was the parameter with the
strongest correlation to HRQoL scores. CONCLUSIONS: Xipho-pubic angle reflects
changes in spinal changes and has strong correlation to HRQoL and spinopelvic
parameters. It can discriminate between patients with minimal, moderate, and
severe disability as measured by ODI scores. These slides can be retrieved under
Electronic Supplementary Material.
PMID- 29330578
TI - [Lichenoid diseases].
PMID- 29330577
TI - Asymptomatic population reference values for three knee patient-reported outcomes
measures: evaluation of an electronic data collection system and implications for
future international, multi-centre cohort studies.
AB - OBJECTIVES: The aim was to assess whether the Knee Society Score, Oxford Knee
Score (OKS) and Knee Injury and Osteoarthritis Outcome Score (KOOS) were
comparable in asymptomatic, healthy, individuals of different age, gender and
ethnicity, across two remote continents. The purpose of this study was to
establish normal population values for these scores using an electronic data
collection system. HYPOTHESIS: There is no difference in clinical knee scores in
an asymptomatic population when comparing age, gender and ethnicity, across two
remote continents. METHODS: 312 Australian and 314 Canadian citizens, aged 18-94
years, with no active knee pain, injury or pathology in the ipsilateral knee
corresponding to their dominant arm, were evaluated. A knee examination was
performed and participants completed an electronically administered questionnaire
covering the subjective components of the knee scores. The cohorts were age- and
gender-matched. Chi-square tests, Fisher's exact test and Poisson regression
models were used where appropriate, to investigate the association between knee
scores, age, gender, ethnicity and nationality. RESULTS: There was a significant
inverse relationship between age and all assessment tools. OKS recorded a
significant difference between gender with females scoring on average 1% lower
score. There was no significant difference between international cohorts when
comparing all assessment tools. CONCLUSIONS: An electronic, multi-centre data
collection system can be effectively utilized to assess remote international
cohorts. Differences in gender, age, ethnicity and nationality should be taken
into consideration when using knee scores to compare to pathological patient
scores. This study has established an electronic, normal control group for future
studies using the Knee society, Oxford, and KOOS knee scores. LEVEL OF EVIDENCE:
Diagnostic Level II.
PMID- 29330579
TI - [Initially undetected de novo psoriasis triggered by nivolumab for metastatic
base of the tongue carcinoma].
AB - Nivolumab is a monoclonal antibody that binds to the PD-1 receptor on T cells and
inhibits the interaction with the PD-L1 and PD-L2 ligands on cancer cells. Thus,
nivolumab has immunostimulatory properties. The known side effects of this
therapy include fatigue, skin rash, dysfunction of the thyroid gland and colitis,
which are explained by the immunoregulatory mechanisms of the drug. Here we
report on the case of a 58-year-old man with metastatic base of tongue carcinoma
who developed de novo psoriasis triggered by nivolumab. The patient was treated
for months with the diagnosis of a generalized mycosis. This case highlights the
importance of vigilance for unexpected cutaneous side effects during immune
stimulating therapy with checkpoint inhibitors.
PMID- 29330580
TI - [Lichen ruber planus : Better understanding, better treatment!]
AB - Lichen ruber, also called lichen ruber planus or lichen planus (LP), is a
noncontagious inflammatory skin disease. LP is the main representative and
namesake of the group of lichenoid diseases, which are characterized by small
papules often accompanied by severe itching. With 65% of cases, LP is primarily a
disease of the mucous membranes. In 20% of the cases, the disease is found on the
skin and mucous membranes; skin involvement alone is seen in only about 10% of
cases. Cutaneous LP has a very favorable 1-year prognosis of almost 80% healing
as opposed to the mucosa and the adnexal organs. Histologically, keratinocytes
with vacuolar degeneration, leaving behind apoptotic Kamino bodies and the
characteristic band-shaped lymphocytic infiltrate at the dermatoepithelial
junction, are common to lichenoid diseases. The horny layer is firm and compact
and the stratum granulosum is thickened as a correlate of the Wickham stripes.
The molecular pathogenesis, still partially hypothetical, assumes trigger factors
leading to the presentation of intrinsic or foreign antigens. The triggered
inflammation becomes independent in the sense of a classical cell-mediated
autoimmune disease. Other autoimmune diseases are often associated with LP.
Classical anti-inflammatory-immunosuppressive therapeutic concepts dominate with
systemic retinoids ranking first in the highest evidence class for cutaneous LP
with limitations in treatment of both mucosal and adnexal LP. More recently,
interesting and new complementary phototherapeutics have been identified.
PMID- 29330581
TI - [Liposuction].
AB - Liposuction began in the 1920s when the Parisian surgeon Charles Dujarier became
interested in body shaping and fat removal. Today, it is estimated that 1,453,000
liposuctions are annually performed worldwide. In Germany, 45,000 liposuctions
are performed annually. The majority of liposuctions are performed as self-pay
services. The aim of this article is to outline the development of liposuction,
to explain the various liposuction procedures and methods, to clarify the
indications for treatment, and point out the complications and pitfalls described
in the literature.
PMID- 29330583
TI - Utilization of Active Surveillance and Watchful Waiting for localized prostate
cancer in the daily practice.
AB - PURPOSE: To analyze the utilization of Active Surveillance (AS) and Watchful
Waiting (WW) in the daily routine setting, since both are non-invasive treatment
options for localized prostate cancer (PCa), which are used in a curative (AS) or
palliative (WW) setting. Since differentiation of both strategies is not always
clear, patients were compared with respect to the inclusion criteria, frequency
of follow-up examinations (Prostate Specific Antigen = PSA tests, rebiopsies),
and initiation of a deferred treatment. METHODS: HAROW is a non-interventional,
health-service research study on the management of localized PCa in the community
setting. Of 3169 patients, prospectively enrolled from 2008 to 2013 with a mean
follow-up of 28.2 months, 468 chose AS and 126 WW. Treating urologists reported
clinical variables, information on therapy and clinical course of disease.
RESULTS: AS patients were significantly younger and had more low-risk tumors. No
differences were seen in the number of PSA tests during follow-up: mean number of
PSA tests was 6.08 for AS- and 5.18 for WW patients, more than four PSA tests
were reported in 63.9% AS- and 59.5% WW patients (p = 0.136). At least one re
biopsy was performed in 39.7% AS- and 9.5% WW patients (p < 0.001).
Discontinuation rates were 23.9% (n = 112) for AS and 11.9% (n = 15) for WW. Most
of the AS patients opted for a curative treatment (prostatectomy = 65,
radiotherapy = 30), whereas 12 WW patients received a palliative hormone therapy
and three patients received radiotherapy. CONCLUSIONS: Physicians seem to
distinguish clearly between AS and WW in terms of inclusion criteria and deferred
therapy, whereas this differentiation tends to become indistinct in terms of
follow-up examinations.
PMID- 29330582
TI - Nano-silicon alters antioxidant activities of soybean seedlings under salt
toxicity.
AB - Materials with a particle size less than 100 nm are classified as nano-materials.
The physical and chemical properties of nano-materials can vary considerably from
those of bulk materials of the same composition. Silicon (Si) still fails to get
recognized as an essential nutrient for plant growth and development, however the
beneficial effects in terms of growth, biotic and abiotic stress resistance have
been indicated in a variety of plant species for their growth. The aim of this
study was to investigate the effects of different nano-silicon rates on the
growth and antioxidant activities of soybean (Glycine max L. cv. M7) under salt
stress. The results showed that salinity decreased shoot and root dry weight,
potassium (K+) concentration in the root and leaf; however, increased sodium
(Na+) concentration, catalase, peroxidase, ascorbate peroxidase and superoxide
dismutase activities, phenolic components, ascorbic acid and alpha-tocopherol
contents, lipid peroxidation, hydrogen peroxide, and oxygen radical's
concentration. Between the treatments, 0.5 and 1 mM of nanosilicon oxide (nano
SiO2) improved shoot and root growth of seedlings. In contrast, a foliar
application of SiO2 at 2 mM reduced the soybean growth. Overall, exogenous nano
silicon alleviated the salt stress by increase in K+ concentration, antioxidant
activities, non-enzymatic compounds and decreasing of Na+ concentration, lipid
peroxidation, and reactive oxygen species production.
PMID- 29330584
TI - A dedicated neurologist at the emergency department during out-of-office hours
decreases patients' length of stay and admission percentages.
AB - BACKGROUND: Emergency departments (EDs) worldwide face crowding, which hampers
patient flow. In this study, the impact of a dedicated neurologist present at the
ED on patient flow during out-of-office hours was assessed. METHODS: A cross
sectional, mixed methods study was undertaken at a Dutch ED, including a pre-post
analysis of data of patients who had a primary neurological disease (n = 458) and
staff surveys (n = 152). Descriptive statistics and content analysis were used
for analyses. RESULTS: Despite a 36% increase in the number of neurological
patients (control period: n = 194, intervention period n = 264), a 30 min per
patient decrease in ED median length of stay (LOS) was reached during the
intervention period. Furthermore, the admission percentage decreased
significantly (57.7% in the control period vs. 47.7% in the intervention period,
p = 0.03). During half of the shifts neurologists stated that their presence had
been valuable. Perceived reasons for this added value mentioned were improved
quality of care, enhanced throughput of patients, and quicker consultations with
other medical specialists. CONCLUSIONS: In our hypothesis-generating study, a
dedicated neurologist present at the ED during out-of-office hours was associated
with decreased patients' LOS and a decreased admission percentage, indicating
increased decisiveness when the neurologist is present at the ED.
PMID- 29330586
TI - Hydrocephalus recurrence and intestinal obstruction due to giant CSF pseudocyst.
PMID- 29330585
TI - Potentially inappropriate medications in community-dwelling older adults
undertaken as a comprehensive geriatric risk assessment.
AB - PURPOSE: The prescription of potentially inappropriate medications (PIMs) is
associated with an increase in adverse events, prescribing cascades, high health
care costs, morbidity, and mortality in the elderly. The overarching objective of
this study is to examine the prevalence of PIMs in the elderly, applying the 2012
American Geriatrics Society Beers criteria for the study period 2012-2014, and
the updated 2015 Beers criteria for 2015. METHODS: The study population (N =
70,479) included a continuously recruited national cohort of community-dwelling
older (aged >= 65 years) New Zealanders who had undertaken the International
Resident Assessment Instrument-Home Care (interRAI-HC) assessments between
September 2012 and October 2015. Exposure of PIMs 90 days before and after
assessment, and 90-180 days after assessment are reported. RESULTS: Exposure to
PIMs was highest in individuals aged over 95 years and in males. The average
number of PIMs prescribed 90 days before assessment during the period 2015 was
marginally higher compared to 2012-2014 (0.19 versus 0.04), and a greater number
of individuals were exposed to one or more PIMs in 2015 compared to 2012-2014
(7.13 versus 2.17%). The prevalence of PIMs 90 days before and after assessment
was 2.17 and 6.92% for 2012-2014, and 7.13 and 24.7% for 2015, respectively. The
percent change in PIMs in 2012-2014 and 2015 after 90 days of assessment were
4.70% (confidence interval (CI) 4.50%, 5.00%, p < 0.001) and 17.60% (95% CI
16.80%, 18.30%, p < 0.001), respectively. The majority of PIMs prescribed
belonged to the therapeutic class of medications acting on the central nervous
system and the gastrointestinal system. CONCLUSION: Geriatric risk assessments
may provide a vital opportunity to review medication lists by multidisciplinary
teams with a view to reducing PIMs and unnecessary polypharmacy in older adults.
Comprehensive geriatric risk assessment has the potential to reduce adverse
medication outcomes and costs associated with inappropriate prescribing in a
vulnerable population of older adults.
PMID- 29330587
TI - Posterior reversible encephalopathy syndrome with spinal cord involvement (PRES
SCI) as a rare complication of severe diabetic ketoacidosis: a case report and
review of the literature.
AB - INTRODUCTION: In addition to diffuse brain oedema, diabetic ketoacidosis (DKA)
can lead to ischaemic or haemorrhagic stroke, extrapontine myelinolysis, and
sinovenous thrombosis. However, posterior reversible encephalopathy syndrome
(PRES) and spinal cord oedema are rarely reported in patients with DKA. METHODS:
We present a case of a 17-year-old-girl who developed headache, blurred vision,
and paraplegia after her DKA was controlled. Sequential magnetic resonance (MR)
scans of the brain and spinal cord were performed. RESULTS: Brain MR showed large
patchy lesions in the bilateral white matter of the parieto-occipital lobes,
which had high T2 signal intensity and low T1 signal intensity. MR scanning of
the spinal cord showed longitudinal confluent central spinal cord T2
hyperintensity spanning seven thoracic spinal segments. With symptomatic
treatment, the patient's headache and vision disturbance subsided within 1 week.
Subsequent MR scans demonstrated that the lesion in the spinal cord had decreased
significantly in 10 days, and the large patchy lesions in the brain disappeared
completely in 2 months. Her paraplegia improved gradually without obvious sequela
3 months later. The evolution of the disease and radiological findings supported
the diagnosis of PRES with spinal cord involvement. CONCLUSION: To the best of
our knowledge, this is the first case report describing PRES with spinal cord
involvement as a complication of DKA. PRES is a rare complication that should be
considered along with other neurological complications of DKA when focal deficits
appear.
PMID- 29330588
TI - Whole-body 3D kinematics of bird take-off: key role of the legs to propel the
trunk.
AB - Previous studies showed that birds primarily use their hindlimbs to propel
themselves into the air in order to take-off. Yet, it remains unclear how the
different parts of their musculoskeletal system move to produce the necessary
acceleration. To quantify the relative motions of the bones during the
terrestrial phase of take-off, we used biplanar fluoroscopy in two species of
birds, diamond dove (Geopelia cuneata) and zebra finch (Taeniopygia guttata). We
obtained a detailed 3D kinematics analysis of the head, the trunk and the three
long bones of the left leg. We found that the entire body assisted the production
of the needed forces to take-off, during two distinct but complementary phases.
The first one, a relatively slow preparatory phase, started with a movement of
the head and an alignment of the different groups of bones with the future take
off direction. It was associated with a pitch down of the trunk and a flexion of
the ankle, of the hip and, to a lesser extent, of the knee. This crouching
movement could contribute to the loading of the leg muscles and store elastic
energy that could be released in the propulsive phase of take-off, during the
extension of the leg joints. Combined with the fact that the head, together with
the trunk, produced a forward momentum, the entire body assisted the production
of the needed forces to take-off. The second phase was faster with mostly
horizontal forward and vertical upward translation motions, synchronous to an
extension of the entire lower articulated musculoskeletal system. It led to the
propulsion of the bird in the air with a fundamental role of the hip and ankle
joints to move the trunk upward and forward. Take-off kinematics were similar in
both studied species, with a more pronounced crouching movement in diamond dove,
which can be related to a large body mass compared to zebra finch.
PMID- 29330589
TI - Impact of valve-less vs. standard insufflation on pneumoperitoneum volume,
inflammation, and peritoneal physiology in a laparoscopic sigmoid resection
experimental model.
AB - BACKGROUND: Standard insufflators compensate for intra-abdominal pressure
variations with pressure spikes. Our aim was to evaluate the impact of a stable,
low-pressure pneumoperitoneum induced by a valve-less insufflator, on working
space, hemodynamics, inflammation, and peritoneal physiology, in a model of
laparoscopic sigmoid resection. MATERIALS AND METHODS: Twelve pigs (47 +/- 3.3
kg) were equipped for invasive hemodynamic monitoring and randomly assigned to
Standard (n = 6) vs. valve-less (n = 6) insufflation. Animals were positioned in
a 30 degrees Trendelenburg on a CT scan bed. A low-pressure pneumoperitoneum (8
mmHg) was started and duration was set for 180 min. Abdominal CT scans were
performed, under neuromuscular blockade, before, immediately after, and 1 and 3 h
after insufflation. Pneumoperitoneum volumes were calculated on 3D reconstructed
CT scans. After creation of a mesenteric window, capillary blood was obtained by
puncturing the sigmoid serosa and local lactatemia (mmol/L) was measured using a
handheld analyzer. Surgical resection was performed according to the level of
lactates, in order to standardize bowel stump perfusion. IL-1 and IL-6 (ng/mL)
were measured repeatedly. The peritoneum was sampled close to the surgical site
and distantly for the oxygraphic assessment of mitochondrial respiration. A
pathologist applied a semi-quantitative score to evaluate the anastomosis.
RESULTS: Mean arterial pressure, pulse, body temperature, oximetry, systemic
lactatemia, and local lactates were similar. IL-6 was lower in the valve-less
group, reaching a statistically significant difference after 3 h of insufflation
(64.85 +/- 32.5 vs. 133.95 +/- 59.73; p = 0.038) and 48 h (77.53 +/- 68.4 vs.
190.74 +/- 140.79; p = 0.029). Peritoneal mitochondrial respiration was
significantly increased after the survival period, with no difference among the
groups. The anastomoses in the valve-less group demonstrated a lower acute (p =
0.04) inflammatory infiltration. The mean anterior posterior thickness was
slightly, yet significantly higher in the valve-less group, on all post
insufflation CT scans. CONCLUSIONS: Valve-less insufflation achieved a slightly
higher working space and a lower systemic and localized inflammatory response in
this experimental setting.
PMID- 29330590
TI - A meta-analysis of pesticide loss in runoff under conventional tillage and no
till management.
AB - Global agricultural intensification has led to increased pesticide use (37-fold
from 1960 to 2005) and soil erosion (14% since 2000). Conservation tillage,
including no-till (NT), has been proposed as an alternative to conventional plow
till (PT) to mitigate soil erosion, but past studies have reported mixed results
on the effect of conservation tillage on pesticide loss. To explore the
underlying factors of these differences, a meta-analysis was conducted using
published data on pesticide concentration and load in agricultural runoff from NT
and PT fields. Peer-reviewed articles (1985-2016) were compiled to build a
database for analysis. Contrary to expectations, results showed greater
concentration of atrazine, cyanazine, dicamba, and simazine in runoff from NT
than PT fields. Further, we observed greater load of dicamba and metribuzin, but
reduced load of alachlor from NT fields. Overall, the concentration and the load
of pesticides were greater in runoff from NT fields, especially pesticides with
high solubility and low affinity for solids. Thus, NT farming affects soil
properties that control pesticide retention and interactions with soils, and
ultimately their mobility in the environment. Future research is needed for a
more complete understanding of pesticide-soil interactions in NT systems. This
research could inform the selection of pesticides by farmers and improve the
predictive power of pesticide transport models.
PMID- 29330592
TI - Genomic characterization of key bacteriophages to formulate the potential
biocontrol agent to combat enteric pathogenic bacteria.
AB - Combating bacterial pathogens has become a global concern especially when the
antibiotics and chemical agents are failing to control the spread due to its
resistance. Bacteriophages act as a safe biocontrol agent by selectively lysing
the bacterial pathogens without affecting the natural beneficial microflora. The
present study describes the screening of prominent enteric pathogens NDK1, NDK2,
NDK3, and NDK4 (Escherichia, Klebsiella, Enterobacter, and Serratia) mostly
observed in domestic wastewater; against which KNP1, KNP2, KNP3, and KNP4 phages
were isolated. To analyze their potential role in eradicating enteric pathogens
and toxicity issue, these bacteriophages were sequenced using next-generation
sequencing and characterized based on its genomic content. The isolated
bacteriophages were homologous to Escherichia phage (KNP1), Klebsiella phage
(KNP2), Enterobacter phage (KNP3), Serratia phage (KNP4), and belonged to
Myoviridae family of Caudovirales except for the unclassified KNP4 phage. Draft
genome analysis revealed the presence of lytic enzymes such as holing and
lysozyme in KNP1 phage, endolysin in KNP2 phage, and endopeptidase with holin in
KNP3 phage. The absence of any lysogenic and virulent genes makes this
bacteriophage suitable candidate for preparation of phage cocktail to combat the
pathogens present in wastewater. However, KNP4 contained a virulent gene
rendering it unsuitable to be used as a biocontrol agent. These findings make the
phages (KNP1-KNP3) as a promising alternative for the biocontrol of pathogens in
wastewater which is the main culprit to spread these dominated pathogens in
different natural water bodies. This study also necessitates for genomic
screening of bacteriophages for lysogenic and virulence genes prior to its use as
a biocontrol agent.
PMID- 29330593
TI - The Pathophysiological Basis and Surgical Management of Ranula are Established:
Reply.
PMID- 29330591
TI - Changes in the lipopolysaccharide of Proteus mirabilis 9B-m (O11a) clinical
strain in response to planktonic or biofilm type of growth.
AB - The impact of planktonic and biofilm lifestyles of the clinical isolate Proteus
mirabilis 9B-m on its lipopolysaccharide (O-polysaccharide, core region, and
lipid A) was evaluated. Proteus mirabilis bacteria are able to form biofilm and
lipopolysaccharide is one of the factors involved in the biofilm formation.
Lipopolysaccharide was isolated from planktonic and biofilm cells of the
investigated strain and analyzed by SDS-PAGE with silver staining, Western
blotting and ELISA, as well as NMR and matrix-assisted laser desorption
ionization time-of-flight mass spectrometry techniques. Chemical and NMR
spectroscopic analyses revealed that the structure of the O-polysaccharide of P.
mirabilis 9B-m strain did not depend on the form of cell growth, but the full
length chains of the O-antigen were reduced when bacteria grew in biofilm. The
study also revealed structural modifications of the core region in the
lipopolysaccharide of biofilm-associated cells-peaks assigned to compounds absent
in cells from the planktonic culture and not previously detected in any of the
known Proteus core oligosaccharides. No differences in the lipid A structure were
observed. In summary, our study demonstrated for the first time that changes in
the lifestyle of P. mirabilis bacteria leads to the modifications of their
important virulence factor-lipopolysaccharide.
PMID- 29330594
TI - Coding valence in touchscreen interactions: hand dominance and lateral movement
influence valence appraisals of emotional pictures.
AB - The Body-Specificity Hypothesis postulates that the space surrounding the
dominant hand is perceived as positive due to the motor fluency of this hand,
whereas the space surrounding the non-dominant hand is perceived as negative.
Experimental studies based on this theoretical framework also revealed
associations between affective valence and hand dominance (i.e., dominant hand
positive; non-dominant hand-negative), or lateral movements of the hands (i.e.,
right hand toward the right space-positive; left hand toward the left space
positive). Interestingly, these associations have not been examined with regard
to how lateral actions of the hands may influence affective experiences as, for
example, in valence appraisals of affective objects that have been manipulated.
The study presented here has considered this question in light of the emerging
interest of embodied cognition approaches to interactive technologies,
particularly in affective experiences with touchscreen interfaces. Accordingly,
right-handed participants evaluated the valence of positive and negative
emotional pictures after interacting with them either with the dominant right or
with the non-dominant left hand. Specifically, they moved the pictures either
from left to right or from right to left sides of a touchscreen monitor. The
results indicated that a valence matching between the hand used for the
interactions, the picture's valence category, and the movement's starting side
reinforced the valence appraisals of the pictures (i.e., positive/negative
pictures were more positively/negatively evaluated). The findings are discussed
against the background of the Theory of Event Coding, which accounts for both the
affective properties of the stimuli and the affective connotation of the related
action.
PMID- 29330595
TI - Consistency, not speed: temporal regularity as a metacognitive cue.
AB - We examined the hypothesis that skilled performance is monitored on the basis of
fluency, where fluency is operationally defined as temporal regularity or
rhythmicity rather than speed. Since error is often associated with variable
timing, we tested the possibility that people use varied timing as a
metacognitive cue. Using a sequential counting task, which may be representative
of the broader class of skilled, multi-step tasks, we found that shifting between
irregular and regular timing led to greater confidence ratings when the timing
associated with the task was regular. We argue that regular, consistent timing,
when compared directly to irregular timing, produced feelings of fluent task
performance, leading to increased confidence. In the first experiment, we
demonstrated that both accuracy and confidence were higher when participants
completed a task presented with regular timing. In the second experiment, we
found a dissociation between accuracy and confidence, strengthening the argument
that individuals relied on monitoring of fluency to support their metacognitive
judgments. In Study 3 and an assessment of naive beliefs, we ruled out
alternative explanations for these findings.
PMID- 29330596
TI - Cognitive functioning: is it all or none?
AB - Under various circumstances, the cognitive system operates in a global manner
that is not very precise and barely discriminatory. This form of operating has
been described via a general principal that Diamond (Developmental Psychology
45:130-138, 2009) has denominated the All or None Hypothesis. This author has
described a set of corollaries derived from this hypothesis that make it possible
to verify it in each one of these domains. Although there is evidence of the
global and non-discriminate way in which the cognitive system operates in
populations of children, to date, there are no studies that have examined whether
this mode of operation is also present in populations of adults. Researchers have
yet to determine whether these corollaries apply to middle-aged adults. For this
reason, this is the current study's principal objective. A sample of 73
participants with ages ranging from 18 to 57 of both genders was evaluated. A
modified version of the arrows test in Davidson et al. (Neuropsychologia 44:2037
2078, 2006) was used to analyze the three corollaries. The results obtained in
this study can be interpreted as evidence in favor of the corollaries analyzed
herein. Furthermore, they indicate that adult populations have a global response
mode that is barely differentiated and that is activated by default in the face
of problems and situations that demand behaviors and/or thoughts that are not
very analytical and differentiated. However, in contexts that demand greater
discrimination, this global mode is substituted by a controlled mode that
requires greater cognitive effort and more differentiated processing.
PMID- 29330597
TI - Inpatient treatment of patients with idiopathic sudden sensorineural hearing
loss: a population-based healthcare research study.
AB - PURPOSE: The aim was to determine inpatient treatment rates of idiopathic sudden
sensorineural hearing loss (ISSNHL) with focus on diagnostics, treatment, and
outcome. METHODS: A retrospective population-based study in the federal state
Thuringia in 2011 and 2012 was performed on all 490 inpatients (51% females,
median age: 60 years) treated for ISSNHL (Median duration: 7 days). The
association between analyzed parameters and the probability of recovery was
tested using univariable and multivariable statistics. RESULTS: The inpatient
treatment rate for ISSNHL was 11.23 per 100,000. 172 patients (35%) had an
outpatient treatment prior to inpatient treatment. For pure-tone audiometry of
the three most affected frequencies (3PTAmax), the initial median hearing loss
was 66.67 dB, the median absolute hearing gain DeltaPTAabs was 10.0 dB, and the
median relative hearing gain in relation with the contralateral side DeltaPTArel
contral was 30.86%. 51% of the patients reached a DeltaPTAabs of >= 10 dB. About
2 of 5 patients recovered to a DeltaPTArel contral >= 50% or reached <= 10 dB of
contralateral ear. The multivariate analysis revealed that an ISSNHL on the left
side [Hazard ratio (HR) = 1.6.88; confidence interval (CI) = 1.161-2.454], no
down-sloping audiogram type (HR = 2.016; CI = 1.391-2.921), and no prior
outpatient prednisolone treatment (HR = 2.374; CI = 1.505-3.745) were independent
factors associated with better recovery (DeltaPTAabs >= 10 dB). CONCLUSION:
Inpatient treatment of ISSNHL is variable in daily practice. The population-based
recovery rate was worse than reported in clinical trials. More standardization
and clearer criteria for outpatient, inpatient, and salvage therapy are needed.
PMID- 29330598
TI - Satisfaction in rhinoplasty: the possible impact of anxiety and functional
outcome.
AB - BACKGROUND: Rhinoplasty is a complex but commonly applied surgical procedure.
Patient satisfaction is the least discussed but one of the most important
determinants of surgical success. OBJECTIVES: Evaluation of the patient
satisfaction together with surgeon satisfaction were the main goals of this
study. The roles of anxiety, gender, age and follow-up period were also studied.
PATIENTS AND METHODS: 53 eligible patients operated by the first two authors
within the previous 2 years were enrolled in the study. The medical records were
reviewed for demographic data as well as the details of the surgical procedure.
Functional and esthetic satisfactions of the patients were evaluated by VAS and
ROE respectively. Surgeon satisfaction was evaluated by VAS in crosswise manner.
Anxiety was measured by STAI_s and STAI_t scales. RESULTS: The analysis
concerning esthetic results as well as functional results did not reveal any
significant difference between the two surgeons (p = 0.132, p = 0.43
respectively). ROE scores were significantly different among patients with "good"
and "very good" functional results. The difference between surgeon satisfaction
and patient satisfaction was found to be insignificant (p = 0.273). Correlation
analysis yielded a positive correlation between STAI_I and STAI_II (Pearson r =
0.335, p = 0.014) but not between STAI scores and ROE scores. Moreover, there was
no relation between anxiety scores and the functional results. Likely, gender as
well as age, follow-up, and surgical technique were not found to have any effect
on patient satisfaction either. CONCLUSION: Patient satisfaction is preferential
in rhinoplasty. In our patient series, patient satisfaction was shown to be
correlated with functional outcome but not with surgeon satisfaction. Anxiety was
not found to have a significant impact on results of rhinoplasty. Our results
should be interpreted cautiously keeping in mind that our patients' primary drive
for rhinoplasty was functional.
PMID- 29330599
TI - Infraorbital foramen localization in orbitozygomatic fractures: a CT study with
intraoperative finding.
AB - OBJECTIVE: The aim of this study was to assess the infraorbital foramen (IOF)
using CT in patients with Zygomaticomaxillary complex (ZMC) fractures (midface
fracture). PATIENTS AND METHODS: This prospective study was carried out on 49
patients had ZMC fractures (98 sides) and 27 patients (54 sides) with
craniomaxillofacial fractures rather than fractured ZMC as a control. Using CT,
position of IOF was documented on 3D view in relation to inferior orbital rim,
tooth root relation and finally with a novel imaginary line passing between
anterior nasal spine and whitnall tubercle. RESULTS: Position of IOF had fixed
anatomical landmark: just lateral to a line drawn between the anterior nasal
spine to whitnall tubercle (clinically between nasal tip-lateral canthal
ligament) and lateral to vertical plane to root of maxillary canine also with
variable distance from inferior orbital rim ranged from 4.56 to 18.03 mm with a
mean of 7.9 +/- 2.447 mm. CONCLUSION: Even though ZMC fractures disturb the
anatomical location of the ZMC bones, there are still preserved reliable fixed
landmarks maxillofacial surgeons can depend on to identify and preserve ION.
PMID- 29330600
TI - The impact of acoustic neuroma on long-term quality-of-life outcomes in the
United Kingdom.
AB - OBJECTIVE: To quantify the impact of acoustic neuroma on the quality-of-life
(QOL) patients in the United Kingdom. STUDY DESIGN: Online questionnaire survey.
PATIENTS: Members of the British Acoustic Neuroma Association received PANQOL
questionnaires. RESULTS: Of the 880 BANA members contacted, 397 (45.1%)
responded, although only 359 had complete datasets for analysis. Composite QOL
scores were as follows: for microsurgery 58 (SD 35), for radiotherapy 56 (SD18),
for combination of surgery and radiotherapy 49 (SD 14), and for the observation
group 54 (SD 20). No statistical significance with ANOVA (p = 0.532). Mean (SD)
composite QOL scores were as follows: for follow-up < 6 52 (SD 18), for follow-up
6-10 55 (SD 20) and follow-up > 10 years 65 (SD 45). Overall, these values were
significantly different compared by ANOVA (p < 0.001). Patients with facial
paralysis showed no statistical significant differences between the different
treatment groups. CONCLUSIONS: Short- (< 6 years) and long-term (> 10 years) QOL
outcomes show no significant differences between the different treatment groups.
PMID- 29330602
TI - Ecosystem carbon emissions from 2015 forest fires in interior Alaska.
AB - BACKGROUND: In the summer of 2015, hundreds of wildfires burned across the state
of Alaska, and consumed more than 1.6 million ha of boreal forest and wetlands in
the Yukon-Koyukuk region. Mapping of 113 large wildfires using Landsat satellite
images from before and after 2015 indicated that nearly 60% of this area was
burned at moderate-to-high severity levels. Field measurements near the town of
Tanana on the Yukon River were carried out in July of 2017 in both unburned and
2015 burned forested areas (nearly adjacent to one-another) to visually verify
locations of different Landsat burn severity classes (low, moderate, or high;
LBS, MBS, HBS). RESULTS: Field measurements indicated that the loss of surface
organic layers in boreal ecosystem fires is a major factor determining post-fire
soil temperature changes, depth of thawing, and carbon losses from the mineral
topsoil layer. Measurements in forest sites showed that soil temperature profiles
to 30 cm depth at burned forest sites were higher by an average of 8-10 degrees
C compared to unburned forest sites. Sampling and laboratory analysis indicated a
65% reduction in soil carbon content and a 58% reduction in soil nitrogen content
in severely burned sample sites compared to soil mineral samples from nearby
unburned spruce forests. CONCLUSIONS: Combined with nearly unprecedented forest
areas severely burned in the Interior region of Alaska in 2015, total ecosystem
fire-related losses of carbon to the atmosphere exceeded most previous estimates
for the state, owing mainly to inclusion of potential "mass wasting" and
decomposition in the mineral soil carbon layer in the 2 years following these
forest fires.
PMID- 29330601
TI - Assessment of vestibular-evoked myogenic potentials and video head impulse test
in type 2 diabetes mellitus patients with or without polyneuropathy.
AB - This study aimed to compare cervical vestibular-evoked myogenic potentials
(cVEMP), ocular vestibular-evoked myogenic potentials (oVEMP) and video head
impulse test (vHIT) results between patients with type 2 diabetes mellitus (DM)
or diabetic polyneuropathy (DPN) and healthy controls to determine vestibular end
organ pathologies. The participants in the present study consisted of three
groups: the type 2 DM group (n = 33 patients), the DPN group (n = 33 patients),
and the age- and sex-matched control group (n = 35). Cervical VEMP, oVEMP and
vHIT were performed for each participant in the study and test results were
compared between the groups. Peak-to-peak amplitudes of cVEMP (p13-n21) and oVEMP
(n10-p15) were significantly lower in the DM and DPN groups than the control
group. The values of vHIT were not statistically different between the groups. To
our knowledge, the present study is the first report investigating oVEMP and
cVEMP responses combined with vHIT findings in patients with DM and DPN.
Vestibular end-organ pathologies can be determined via clinical vestibular
diagnostic tools in spite of prominent vestibular symptoms in patients with type
2 DM as well as patients with DPN.
PMID- 29330603
TI - Magnetic covalent triazine-based frameworks as magnetic solid-phase extraction
adsorbents for sensitive determination of perfluorinated compounds in
environmental water samples.
AB - Covalent organic frameworks (COFs), which are a new type of carbonaceous
polymeric material, have attracted great interest because of their large surface
area and high chemical and thermal stability. However, to the best of our
knowledge, no work has reported the use of magnetic COFs as adsorbents for
magnetic solid-phase extraction (MSPE) to enrich and determine environmental
pollutants. This work aims to investigate the feasibility of using covalent
triazine-based framework (CTF)/Fe2O3 composites as MSPE adsorbents to enrich and
analyze perfluorinated compounds (PFCs) at trace levels in water samples. Under
the optimal conditions, the method developed exhibited low limits of detection
(0.62-1.39 ng.L-1), a wide linear range (5-4000 ng L-1), good repeatability (1.12
9.71%), and good reproducibility (2.45-7.74%). The new method was successfully
used to determine PFCs in actual environmental water samples. MSPE based on
CTF/Fe2O3 composites exhibits potential for analysis of PFCs at trace levels in
environmental water samples. Graphical abstract Magnetic covalent triazine-based
frameworks (CTFs) were used as magnetic solid-phase extraction adsorbents for the
sensitive determination of perfluorinated compounds in environmental water
samples. PFBA perfluorobutyric acid, PFBS perfluorobutane sulfonate, PFDA
perfluorodecanoic acid, PFDoA perfluorododecanoic acid, PFHpA perfluoroheptanoic
acid, PFHxA perfluorohexanoic acid, PFHxS perfluorohexane sulfonate, PFNA
perfluorononanoic acid, PFOA perfluorooctanoic acid, PFPeA perfluoropentanoic
acid, PFUdA Perfluoroundecanoic acid.
PMID- 29330605
TI - Membrane-Ion Interactions.
AB - Biomembranes assemble and operate at the interface with electrolyte solutions.
Interactions between ions in solutions and the lipid affect the membrane
structure, dynamics and electrostatic potential. In this article, I review some
of the experimental and computational methods that are used to study membrane
ions interactions. Experimental methods that account for membrane-ion
interactions directly and indirectly are presented first. Then, studies in which
molecular dynamics simulations were used to gain an understanding of membrane-ion
interactions are surveyed. Finally, the current view on membrane-ion interactions
and their significance is briefly discussed.
PMID- 29330604
TI - Driving Forces of Translocation Through Bacterial Translocon SecYEG.
AB - This review focusses on the energetics of protein translocation via the Sec
translocation machinery. First we complement structural data about SecYEG's
conformational rearrangements by insight obtained from functional assays. These
include measurements of SecYEG permeability that allow assessment of channel
gating by ligand binding and membrane voltage. Second we will discuss the power
stroke and Brownian ratcheting models of substrate translocation and the role
that the two models assign to the putative driving forces: (i) ATP (SecA) and GTP
(ribosome) hydrolysis, (ii) interaction with accessory proteins, (iii) membrane
partitioning and folding, (iv) proton motive force (PMF), and (v) entropic
contributions. Our analysis underlines how important energized membranes are for
unravelling the translocation mechanism in future experiments.
PMID- 29330606
TI - The associations of poor psychiatric well-being among incarcerated men with
injecting drug use histories in Victoria, Australia.
AB - BACKGROUND: Dual substance dependence and psychiatric and psychological
morbidities are overrepresented in prison populations and associated with
reoffending. In the context of an increasing prison population in Australia,
investigating the needs of vulnerable people in prison with a dual diagnosis can
help inform in-prison screening and treatment and improve prison and community
service integration and continuation of care. In this study we quantified
psychiatric well-being in a sample of people in prison with a history of
injecting drug use in Victoria, Australia, and identified factors associated with
this outcome. METHODS AND RESULTS: Data for this paper come from baseline
interviews undertaken in the weeks prior to release as part of a prospective
cohort study of incarcerated men who reported regular injecting drug use prior to
their current sentence. Eligible participants completed a researcher-administered
structured questionnaire that canvassed a range of issues. Psychiatric well-being
was assessed using the 12-item General Health Questionnaire (GHQ-12) and
potential correlates were included based on a review of the literature. Of the
317 men included for analyses, 139 were classified as experiencing current poor
psychiatric well-being. In the multivariate model using modified logistic
regression, history of suicide attempt (aOR = 1.36, 95%CI 1.03-1.78), two or more
medical conditions (aOR = 1.87, 95%CI 1.30-2.67) and use of crystal
methamphetamine in the week prior to their current sentence (aOR = 1.52, 95%CI
1.05-2.22) were statistically significantly associated with current poor
psychiatric well-being. CONCLUSIONS: Comprehensively addressing the health
related needs for this vulnerable population will require a multidisciplinary
approach and enhancing opportunities to screen and triage people in prison for
mental health and other potential co-occurring health issues will provide
opportunities to better address individual health needs and reoffending risk.
PMID- 29330607
TI - River Continuity Restoration and Diadromous Fishes: Much More than an Ecological
Issue.
AB - Ecosystem fragmentation is a serious threat to biodiversity and one of the main
challenges in ecosystem restoration. River continuity restoration (RCR) has often
targeted diadromous fishes, a group of species supporting strong cultural and
economic values and especially sensitive to river fragmentation. Yet it has
frequently produced mixed results and diadromous fishes remain at very low levels
of abundance. Against this background, this paper presents the main challenges
for defining, evaluating and achieving effective RCR. We first identify
challenges specific to disciplines. In ecology, there is a need to develop
quantitative and mechanistic models to support decision making, accounting for
both direct and indirect impacts of river obstacles and working at the river
catchment scale. In a context of dwindling abundances and reduced market value,
cultural services provided by diadromous fishes are becoming increasingly
prominent. Methods for carrying out economic quantification of non-market values
of diadromous fishes become ever more urgent. Given current challenges for rivers
to meet all needs sustainably, conflicts arise over the legitimate use of water
resources for human purposes. Concepts and methods from political science and
geography are needed to develop understandings on how the political work of
public authorities and stakeholders can influence the legitimacy of restoration
projects. Finally, the most exciting challenge is to combine disciplinary
outcomes to achieve a multidisciplinary approach to RCR. Accordingly, the co
construction of intermediary objects and diagrams of flows of knowledge among
disciplines can be first steps towards new frameworks supporting restoration
design and planning.
PMID- 29330608
TI - Environmental Performance Information Use by Conservation Agency Staff.
AB - Performance-based conservation has long been recognized as crucial to improving
program effectiveness, particularly when environmental conditions are dynamic.
Yet few studies have investigated the use of environmental performance
information by staff of conservation organizations. This article identifies
attitudinal, policy and organizational factors influencing the use of a type of
performance information-water quality information-by Soil and Water Conservation
District staff in the Upper Mississippi River Basin region. An online survey (n =
277) revealed a number of important variables associated with greater information
use. Variables included employees' prosocial motivation, or the belief that they
helped people and natural resources through their job, the perceived
trustworthiness of data, the presence of a U.S. Clean Water Act Total Maximum
Daily Load standard designation, and staff discretion to prioritize programs
locally. Conservation programs that retain motivated staff and provide them the
resources and flexibility to plan and evaluate their work with environmental data
may increase conservation effectiveness under changing conditions.
PMID- 29330609
TI - Determination of Appropriate Service Delivery Level for Quantitative Attributes
of Household Toilets in Rural Settlements of India from Users' Perspective.
AB - Improvement of quality of sanitation services in rural settlements is an
important development goal in developing countries including India and
accordingly several strategies are adopted which promote the demand and use of
household toilets through creating awareness and providing subsidies to poor
people for construction of household toilets with service-level standards
specified from experts' perspective. In many cases, users are unsatisfied with
the quality of toilets constructed using subsidies and the same remain unused.
Users' satisfaction depends on their perceptions of service quality of individual
attributes and overall service quality of the household toilets, which is an
important determinant of sustainability and sustained use of toilets. This study
aims to assess and benchmark the appropriate service delivery level for
quantitative attributes of rural household toilets based on user perception. The
service quality is determined with the help of level of service (LOS) scales
developed using successive interval scaling technique, the zone of tolerance
(ZOT), and users satisfaction level (USL) which relates service delivery levels
with user satisfaction directly. The study finds that the service quality of most
of the attributes of household toilets constructed using subsidies is perceived
as poor. The results also suggest that most of the users expect to have a toilet
with the service level of attributes ranging between LOS A and LOS B.
PMID- 29330610
TI - Nutrition delivery of a model-based ICU glycaemic control system.
AB - BACKGROUND: Hyperglycaemia is commonplace in the adult intensive care unit (ICU),
associated with increased morbidity and mortality. Effective glycaemic control
(GC) can reduce morbidity and mortality, but has proven difficult. STAR is a
proven, effective model-based ICU GC protocol that uniquely maintains normo
glycaemia by changing both insulin and nutrition interventions to maximise
nutrition in the context of GC in the 4.4-8.0 mmol/L range. Hence, the level of
nutrition it provides is a time-varying estimate of the patient-specific ability
to take up glucose. METHODS: First, the clinical provision of nutrition by STAR
in Christchurch Hospital, New Zealand (N = 221 Patients) is evaluated versus
other ICUs, based on the Cahill et al. survey of 158 ICUs. Second, the inter- and
intra- patient variation of nutrition delivery with STAR is analysed. Nutrition
rates are in terms of percentage of caloric goal achieved. RESULTS: Mean
nutrition rates clinically achieved by STAR were significantly higher than the
mean and best ICU surveyed, for the first 3 days of ICU stay. There was large
inter-patient variation in nutrition rates achieved per day, which reduced
overtime as patient-specific metabolic state stabilised. Median intra-patient
variation was 12.9%; however, the interquartile range of the mean per-patient
nutrition rates achieved was 74.3-98.2%, suggesting patients do not deviate much
from their mean patient-specific nutrition rate. Thus, the ability to tolerate
glucose intake varies significantly between, rather than within, patients.
CONCLUSIONS: Overall, STAR's protocol-driven changes in nutrition rate provide
higher nutrition rates to hyperglycaemic patients than those of 158 ICUs from 20
countries. There is significant inter-patient variability between patients to
tolerate and uptake glucose, where intra-patient variability over stay is much
lower. Thus, a best nutrition rate is likely patient specific for patients
requiring GC. More importantly, these overall outcomes show high nutrition
delivery and safe, effective GC are not exclusive and that restricting nutrition
for GC does not limit overall nutritional intake compared to other ICUs.
PMID- 29330611
TI - A comparison of different sealants preventing demineralization around brackets.
AB - AIM: Aim of the study was to compare how six different sealants resisted thermal,
mechanical, and chemical loading in vitro. MATERIALS AND METHODS: In all, 120
extracted human, nondecayed molars were divided into six groups (20 samples each)
and embedded in resin blocks. The buccal surfaces of the tooth samples were
polished and divided into three areas. Area A contained the product to be
analyzed, area B was covered with colorless nail varnish (negative control), and
area C remained untreated (positive control). The samples were stored in 0.1%
thymol solution. To simulate a 3-month thermomechanical load, the samples were
subjected to thermal cycling and a cleaning device. After 7 days incubation in a
ten Cate demineralization solution (pH value: 4.6), the samples were dissected
using a band saw and the lesion depths and demineralization areas were evaluated
and compared microscopically. RESULTS: The tooth surfaces treated with PRO
SEAL(r) showed no demineralization. Mean lesion depths of 108.1, 119.9, 154.9,
149.2, and 184.5 MUm were found with Alpha-Glaze(r), Seal&Protect(r),
Tiefenfluorid(r), Protecto(r), and Fluor Protector, respectively. There was a
significant difference between PRO SEAL(r) and the other products (p > 0.0001).
There was no significant difference between the other products. CONCLUSION: PRO
SEAL(r) resisted thermal, mechanical, and chemical loading in vitro, providing
protection against white spot lesions.
PMID- 29330613
TI - [Bone replacement materials and antibiotics in revision surgery].
PMID- 29330612
TI - Analysis of the stomatognathic system of children according orthodontic treatment
needs.
AB - PURPOSE: The present study evaluated electromyographic activity (EMG),
masticatory performance, and tongue strength in children without and with
orthodontic treatment needs. PATIENTS AND METHODS: A total of 90 children were
screened and divided into the following groups: Group I (no treatment needed;
mean age: 8.00 +/- 0.43 years; n = 26), Group II (few malocclusions, treatment
needed; mean age: 8.89 +/- 0.43 years; n = 28), and Group III (slight-to
borderline treatment needed; mean age: 8.44 +/- 0.22 years; n = 36). Orthodontic
treatment need was classified on the basis of IOTN-DHC (Index of Orthodontic
Treatment Need - Dental Health Component). The electromyographic Trigno EMG
Systems was used for muscle analysis and the Iowa Oral Pressure Instrument (IOPI)
was used to measure tongue strength. Data were analyzed using normality tests and
one-way analysis of variance with a Bonferroni post hoc test (p <= 0.05).
RESULTS: EMG in almost all mandibular movements was higher in Group III with
statistically significant differences compared to position at rest: right
masseter (p = 0.03); protrusion: left temporal (p = 0.02); saliva swallowing:
left temporal (p = 0.05) and water swallowing: orbicularis oris mouth, right
upper segment (p = 0.05). Lower masticatory performance was found in Group III,
but the difference compared to Group I and II was not significant. There were no
significant differences between the groups in terms of tongue strength.
CONCLUSIONS: Children with borderline orthodontic treatment needs show functional
disorders of the stomatognathic system.
PMID- 29330615
TI - The parameter identification problem for SIR epidemic models: identifying
unreported cases.
AB - A SIR epidemic model is analyzed with respect to identification of its
parameters, based upon reported case data from public health sources. The
objective of the analysis is to understand the relation of unreported cases to
reported cases. In many epidemic diseases the ratio of unreported to reported
cases is very high, and of major importance in implementing measures for
controlling the epidemic. This ratio can be estimated by the identification of
parameters for the model from reported case data. The analysis is applied to
three examples: (1) the Hong Kong seasonal influenza epidemic in New York City in
1968-1969, (2) the bubonic plague epidemic in Bombay, India in 1906, and (3) the
seasonal influenza epidemic in Puerto Rico in 2016-2017.
PMID- 29330616
TI - [Magnetic resonance cisternography].
AB - CLINICAL/METHODICAL ISSUE: Conventional MRI can be insufficient to depict certain
pathologies of the cerebrospinal fluid (CSF)-filled spaces. STANDARD RADIOLOGICAL
METHODS: 3-D T2-weighted sequences and phase-contrast imaging have a high
sensitivity for pathologies of the CSF-filled spaces, but are susceptible to
artifacts in some cases. METHODICAL INNOVATIONS/PERFORMANCE: Magnetic resonance
(MR) cisternography directly depicts the connection between CSF-filled spaces.
PMID- 29330614
TI - Effect of ancymidol on cell wall metabolism in growing maize cells.
AB - MAIN CONCLUSION: Ancymidol inhibits the incorporation of cellulose into cell
walls of maize cell cultures in a gibberellin-independent manner, impairing cell
growth; the reduction in the cellulose content is compensated with xylans.
Ancymidol is a plant growth retardant which impairs gibberellin biosynthesis. It
has been reported to inhibit cellulose synthesis by tobacco cells, based on its
cell-malforming effects. To ascertain the putative role of ancymidol as a
cellulose biosynthesis inhibitor, we conducted a biochemical study of its effect
on cell growth and cell wall metabolism in maize cultured cells. Ancymidol
concentrations <= 500 uM progressively reduced cell growth and induced globular
cell shape without affecting cell viability. However, cell growth and viability
were strongly reduced by ancymidol concentrations >= 1.5 mM. The I50 value for
the effect of ancymidol on FW gain was 658 uM. A reversal of the inhibitory
effects on cell growth was observed when 500 uM ancymidol-treated cultures were
supplemented with 100 uM GA3. Ancymidol impaired the accumulation of cellulose in
cell walls, as monitored by FTIR spectroscopy. Cells treated with 500 uM
ancymidol showed a ~ 60% reduction in cellulose content, with no further change
as the ancymidol concentration increased. Cellulose content was partially
restored by 100 uM GA3. Radiolabeling experiments confirmed that ancymidol
reduced the incorporation of [14C]glucose into alpha-cellulose and this reduction
was not reverted by the simultaneous application of GA3. RT-PCR analysis
indicated that the cellulose biosynthesis inhibition caused by ancymidol is not
related to a downregulation of ZmCesA gene expression. Additionally, ancymidol
treatment increased the incorporation of [3H]arabinose into a hemicellulose
enriched fraction, and up-regulated ZmIRX9 and ZmIRX10L gene expression,
indicating an enhancement in the biosynthesis of arabinoxylans as a compensatory
response to cellulose reduction.
PMID- 29330617
TI - Characterizing genomic differences of human cancer stratified by the TP53
mutation status.
AB - The key roles of the TP53 mutation in cancer have been well established. TP53 is
the most frequently mutated gene, and its inactivation is widespread among human
cancer types. However, the landscape of genomic alterations in human cancers
stratified by the TP53 mutation has not yet been described. We obtained somatic
mutation and copy number change data of 6551 regular-mutated samples from the
Cancer Genome Atlas (TCGA) and compared significantly mutated genes (SMGs), copy
number alterations, mutational signatures and mutational strand asymmetries
between cancer samples with and without the TP53 mutation. We identified 126
SMGs, 30 of which were statistically significant in both the TP53 mutant and wild
type groups. Several SMGs, such as VHL, SMAD4 and PTEN, showed a mutation bias
towards the TP53 wild-type group, whereas ATRX, IDH1 and RB1 were more prevalent
in the TP53 mutant group. Five mutational signatures were extracted from the
combined TCGA dataset on which mutational asymmetry analysis was performed,
revealing that the TP53 mutant group exhibited substantially greater replication
and transcription biases. Furthermore, we found that alterations of multiple
genes in a merged mutually exclusive network composed of BRAF, EGFR, PAK1,
PIK3CA, PTEN, APC and TERT were related to shortened survival in the TP53 wild
type group. In summary, we characterized the genomic differences and similarities
underlying human cancers stratified by the TP53 mutation and identified multi
gene alterations of a merged mutually exclusive network to be a poor prognostic
factor for the TP53 wild-type group.
PMID- 29330618
TI - Oleic acid chlorohydrin, a new early biomarker for the prediction of acute
pancreatitis severity in humans.
AB - BACKGROUND: The early prediction of the severity of acute pancreatitis still
represents a challenge for clinicians. Experimental studies have revealed the
generation of specific halogenated lipids, in particular oleic acid chlorohydrin,
in the early stages of acute pancreatitis. We hypothesized that the levels of
circulating oleic acid chlorohydrin might be a useful early prognostic biomarker
in acute pancreatitis in humans. METHODS: In a prospective, multicenter cohort
study, plasma samples collected within 24 h after presentation in the emergency
room from 59 patients with acute pancreatitis and from 9 healthy subjects were
assessed for oleic acid chlorohydrin levels. RESULTS: Pancreatitis was mild in 30
patients, moderately severe in 16 and severe in 13. Oleic acid chlorohydrin
levels within 24 h after presentation were significantly higher in patients that
later progressed to moderate and severe acute pancreatitis. Using 7.49 nM as the
cutoff point, oleic acid chlorohydrin distinguished mild from moderately severe
to-severe pancreatitis with high sensitivity/specificity (96.6/90.0%) and
positive/negative predictive values (90.3/96.4%). Using 32.40 nM as the cutoff
value sensitivity, specificity, positive and negative predictive values were all
100% for severe acute pancreatitis. It was found to be a better prognostic marker
than BISAP score, hematocrit at 48 h, SIRS at admission, persistent SIRS or C
reactive protein at 48 h. CONCLUSIONS: Oleic acid chlorohydrin concentration in
plasma is elevated in patients with acute pancreatitis on admission and
correlates with a high degree with the final severity of the disease, indicating
that it has potential to serve as an early prognostic marker for acute
pancreatitis severity.
PMID- 29330619
TI - MR arthrography of the hip: diagnostic performance and image quality of 3D-steady
state free precession versus 2D turbo spin echo sequences.
AB - OBJECTIVE: To retrospectively compare the diagnostic performance of isotropic 3D
steady-state free precession (3D-SSFP) sequences with 2D turbo spin-echo proton
density-weighted fat-saturated (2D-TSE-PD fs) images in hip magnetic resonance
arthrography; arthroscopy was a standard of reference. METHODS: Eighty-one
patients with suspected labral tears who underwent hip MR arthrography (3-T
scanner) were included. 2D-TSE-PD fs sequences were acquired in three planes and
a singular sagittal 3D-SSFP. Labral tears, cartilage pathology and bone marrow
were independently assessed by two blinded radiologists using a 5-point Likert
scale. Accuracy was determined in 39 patients using invasive arthroscopy.
RESULTS: Diagnostic confidence of labral and cartilaginous pathologies based on
image quality was rated higher for 3D-SSFP (4.5 +/- 0.8; 4.35 +/- 0.7; p <
0.0001), but inferior for bone marrow pathology (3.9 +/- 0.7; 4.0 +/- 0.7; p <
0.0001). In the arthroscopy patients, similar sensitivity (85.9%) but higher
specificity (74.4vs.42.9%) and higher positive and negative predictive values
were found in 3D-SSFP of labral and cartilage pathologies. CONCLUSIONS: 3D-SSFP
in hip magnetic resonance arthrography offers increased accuracy in detecting
labral and cartilage pathologies compared with 2D-TSE-PD, while reducing the
acquisition time. A drawback of 3D-SSFP was the inferior diagnostic confidence
for bone marrow evaluation; thus, 3D-SSFP should be combined with conventional 2D
TSE sequences.
PMID- 29330621
TI - Nonuniversal behaviour of helical two-dimensional three-component turbulence.
AB - The dynamics of two-dimensional three-component (2D3C) flows is relevant to
describe the long-time evolution of strongly rotating flows and/or of conducting
fluids with a strong mean magnetic field. We show that in the presence of a
strong helical forcing, the out-of-plane component ceases to behave as a passive
advected quantity and develops a nontrivial dynamics which deeply changes its
large-scale properties. We show that a small-scale helicity injection correlates
the input on the 2D component with the one on the out-of-plane component. As a
result, the third component develops a nontrivial energy transfer. The latter is
mediated by homochiral triads, confirming the strong 3D nature of the leading
dynamical interactions. In conclusion, we show that the out-of-plane component in
a 2D3C flow enjoys strong nonuniversal properties as a function of the degree of
mirror symmetry of the small-scale forcing.
PMID- 29330620
TI - Impact of sirtuin-1 expression on H3K56 acetylation and oxidative stress: a
double-blind randomized controlled trial with resveratrol supplementation.
AB - AIMS: Sirtuin-1 (SIRT-1) down-regulation in type 2 diabetes mellitus (T2DM) has
been associated with epigenetic markers of oxidative stress. We herein aim to
evaluate whether an increase in SIRT-1 expression affects histone 3 acetylation
at the 56 lysine residue (H3K56ac) in T2DM patients randomly selected to receive
either resveratrol (40 mg or 500 mg) or a placebo for 6 months. The primary
outcome is changes in the H3K56ac level by variation in SIRT-1 expression and the
secondary outcome is the evidence of association between SIRT-1 level,
antioxidant markers (TAS), and metabolic variables. METHODS AND RESULTS: At
baseline, peripheral blood mononuclear cell H3K56ac values among the SIRT-1
tertiles did not differ. At trial end, SIRT-1 levels were significantly higher in
patients receiving 500 mg resveratrol. At follow-up, patients were divided into
tertiles of delta (trial end minus baseline) SIRT-1 value. Significant reductions
in H3K56ac and body fat percentage were found in the highest tertile as were
increased TAS levels. A multiple logistic regression model showed that the
highest delta SIRT-1 tertile was inversely associated with variations in H3K56ac
(OR = 0.66; 95% CI 0.44-0.99), TAS (OR = 1.01; 95% CI 1.00-1.02), and body fat
percentage (OR = 0.75; 95% CI 0.58-0.96). CONCLUSIONS: We provide new knowledge
on H3K56ac and SIRT-1 association in T2DM. These data suggest that boosting SIRT
1 expression/activation may impact redox homeostasis in these patients.
ClinicalTrials.gov Identifier NCT02244879.
PMID- 29330622
TI - Association of soil potassium and sodium concentrations with spatial disparities
of prevalence and mortality rates of hypertensive diseases in the USA.
AB - Crop available soil potassium is generally low and on the decline in the
southeastern states of the USA because of the increasing crop and runoff removal
and decreasing application of potassium fertilizer. Hypertension-related
mortality rates are also high in the southeastern states and are on the rise.
Among 41 elements analyzed from 4856 sites across all 48 states, potassium is
identified as the only independent element whose soil concentration has
significant association with spatial disparities of essential hypertension and
hypertension-related mortality rates in the 48 states between 1999 and 2014.
Essential hypertension and hypertension-related mortality rates of the 6 states
with the lowest soil potassium concentration are about 50-26% higher than that of
the 6 states with the highest soil potassium concentration in the 48 states (RR:
1.50, 1.26, low CI 95% 1.47, 1.25 and upper CI 95% 1.53, 1.27, respectively).
Though sodium was not identified as an independent factor, an apparent
significant inverse correlation exists between hypertension prevalence rates and
soil sodium concentration in the 48 states (r = - 0.66, p = 0.00). There likely
has been a decline of potassium in USA produces per unit weight over time and a
likely association between this decline and increasing hypertension rate,
particularly in the southeastern states. Hence, results of this study suggest the
need of increasing potassium intakes for reducing hypertension-related mortality
rates in the southeastern states. Results of this study also support further
examination of potential benefits of sodium from mixture of non-chloride salts in
natural produces.
PMID- 29330623
TI - Comment on a meta-analysis evaluating the cardiac toxicity of lapatinib in
patients with breast cancer and other HER2-positive cancers.
PMID- 29330624
TI - Functional transcriptomic annotation and protein-protein interaction network
analysis identify NEK2, BIRC5, and TOP2A as potential targets in obese patients
with luminal A breast cancer.
AB - PURPOSE: Although obesity is a risk factor for breast cancer, little effort has
been made in the identification of druggable molecular alterations in obese
breast cancer patients. Tumors are controlled by their surrounding
microenvironment, in which the adipose tissue is a main component. In this work,
we intended to describe molecular alterations at a transcriptomic and protein
protein interaction (PPI) level between obese and non-obese patients. METHODS AND
RESULTS: Gene expression data of 269 primary breast tumors were compared between
normal-weight (BMI < 25, n = 130) and obese (IMC > 30, n = 139) patients. No
significant differences were found for the global breast cancer population.
However, within the luminal A subtype, upregulation of 81 genes was observed in
the obese group (FC >= 1.4). Next, we explored the association of these genes
with patient outcome, observing that 39 were linked with detrimental outcome.
Their PPI map formed highly compact cluster and functional annotation analyses
showed that cell cycle, cell proliferation, cell differentiation, and cellular
response to extracellular stimuli were the more altered functions. Combined
analyses of genes within the described functions are correlated with poor
outcome. PPI network analyses for each function were to search for druggable
opportunities. We identified 16 potentially druggable candidates. Among them,
NEK2, BIRC5, and TOP2A were also found to be amplified in breast cancer,
suggesting that they could act as strategic players in the obese-deregulated
transcriptome. CONCLUSION: In summary, our in silico analysis describes molecular
alterations of luminal A tumors and proposes a druggable PPI network in obese
patients with potential for translation to the clinical practice.
PMID- 29330625
TI - Facilitating adherence to endocrine therapy in breast cancer: stability and
predictive power of treatment expectations in a 2-year prospective study.
AB - PURPOSE: To identify modifiable factors predictive of long-term adherence to
adjuvant endocrine therapy (AET). METHODS: As part of a 2-year cohort study in
primary care (n = 116), we investigated whether initial treatment expectations
predict adherence at 24 months after controlling for demographic, medical, and
psychosocial variables. Treatment expectations were measured as necessity-concern
beliefs, expected side-effect severity, and expected coping with side effects.
Their stability over time and differences of trajectories between the adherent
and nonadherent group were examined. RESULTS: Nonadherence at 24 months was 14.7%
(n = 17). Side-effect severity at 3 months [OR 0.25, 95% CI (0.08, 0.81), p =
0.02] and necessity-concern beliefs [OR 2.03, 95% CI (1.11, 3.72), p = 0.02] were
the sole predictors of adherence. Necessity-concern beliefs remained stable over
2 years, whereas expected side-effect severity (p = 0.01, eta p2 = 0.07) and
expected coping with side effects became less optimistic over time (p < 0.001,
eta p2 = 0.19), the latter particularly among nonadherers (p < 0.01, eta p2 =
0.10). CONCLUSIONS: Patients' initial necessity-concern beliefs about the AET and
early severity of side effects affect long-term adherence. Expecting poor
management of side effects may also facilitate nonadherence. We suggest that
discussing benefits, addressing concerns of AET, and providing side-effect coping
strategies could constitute a feasible and promising option to improve adherence
in clinical practice.
PMID- 29330626
TI - Low-frequency rTMS in the superior parietal cortex affects the working memory in
horizontal axis during the spatial task performance.
AB - Spatial working memory has been extensively investigated with different tasks,
treatments, and analysis tools. Several studies suggest that low frequency of the
repetitive transcranial magnetic stimulation (rTMS) applied to the parietal
cortex may influence spatial working memory (SWM). However, it is not yet known
if after low-frequency rTMS applied to the superior parietal cortex, according to
Pz electroencephalography (EEG) electrode, would change the orientation
interpretation about the vertical and horizontal axes coordinates in an SWM task.
The current study aims at filling this gap and obtains a better understanding of
the low-frequency rTMS effect in SWM. In this crossover study, we select 20
healthy subjects in two conditions (control and 1-Hz rTMS). The subjects
performed an SWM task with two random coordinates. Our results presented that low
frequency rTMS applied over the superior parietal cortex may influence the SWM to
lead to a larger distance of axes interception point (p < 0.05). We conclude that
low-frequency rTMS over the superior parietal cortex (SPC) changes the SWM
performance, and it has more predominance in horizontal axis.
PMID- 29330628
TI - Clinical and CN-SFEMG evaluation of neostigmine test in myasthenia gravis.
AB - Neostigmine test (NT) is a pharmacological test, demonstrating a clinical
improvement in patients affected by myasthenia gravis (MG). We aim to compare
clinical evaluation and neurophysiological recordings by concentric-needle single
fiber electromyography (CN-SFEMG) in response to acute administration of
neostigmine in ocular and generalized MG patients. Twenty-three MG patients (10
with ocular MG and 13 with generalized MG) were evaluated before and after 90 min
neostigmine 0.5-mg administration. Clinical responsiveness was assessed by MG
composite (MGC) scale. Neurophysiological evaluation by CN-SFEMG considered
analysis of mean value of consecutive differences (MCD), single-pair jitter, and
blocks. MGC scores significantly improved after NT in generalized MG patients
(MGC 11.1 +/- 7.6 vs 9.1 +/- 6.7, p = 0.02), whereas the improvement was not
significant in the ocular group. CN-SFEMG recordings significantly improved after
NT in generalized MG patients (MCD 58.9 +/- 18.8 vs 45.9 +/- 23.2 MUs, p = 0.003;
single-pair jitter 49.8 +/- 26.9 vs 24.1 +/- 26.7%, p = 0.0001; blocks 6.2 +/-
9.5 vs 2.6 +/- 7.4%, p = 0.03) as well as in ocular MG patients (MCD 50.8 +/-
22.7 vs 40.1 +/- 22.9 MUs, p = 0.01; single-pair jitter 35.9 +/- 23.7 vs 20.0 +/-
25.1%, p = 0.001). CN-SFEMG is a reliable tool to evaluate responsiveness to
acute administration of neostigmine in MG. Moreover, neurophysiological
modifications to NT could show subclinical improvement in ocular MG better than
that of the clinical scale.
PMID- 29330629
TI - Giant left atrial myxoma causing acute ischemic stroke in a child.
AB - Ischemic stroke is uncommon in pediatric populations and is sometimes caused by
cardiac myxoma. In such cases, neurological deficits initially present in
ischemic stroke due to emboli or thrombi of the myxoma. Echocardiography is
helpful to diagnose myxoma in a timely manner and allows urgent surgical
resection of the myxoma. We report a successful case of myxoma in a 7-year-old
boy who initially presented with left-sided hemiparesis.
PMID- 29330630
TI - Evaluation of pain during high-intensity focused ultrasound ablation of benign
thyroid nodules.
AB - OBJECTIVE: To assess severity and factors of pain during high-intensity focused
ultrasound (HIFU) ablation of benign thyroid nodules. METHODS: 128 patients who
underwent a HIFU ablation for a benign thyroid nodule were analysed. All patients
received a bolus of intravenous pethidine and diazepam before treatment. After
treatment, patients were asked to rate their overall pain experience on a visual
analogue scale (0-100) (0 = no pain; 100 = worse possible pain) during treatment,
2 h after treatment and the following morning. Binary logistic regression was
performed to evaluate associated factors for pain including patient demographics,
nodule size, body mass index (BMI) and treatment parameters. RESULTS: At T1,
median (range) pain score was 65.0 (0.00-100.00). Only 16 (12.5 %) patients had a
pain score of zero. In multivariate analysis, only lower BMI (OR 1.265, 95 % CI
1.102-1.452, p=0.001) and longer nodule diameter (OR 1.462, 95 % CI 1.071-1.996,
p=0.017) were independent factors for pain score at T1 <= 65.0. CONCLUSIONS: A
moderate to severe amount of pain was reported during ablation of benign thyroid
nodules in over 50 % of patients. Patients' BMI and length of nodule diameter
were independent variables for pain during HIFU ablation. KEY POINTS: * Pain was
moderate to severe during HIFU ablation of thyroid nodules. * Only one in eight
patients reported no pain during ablation. * Level of energy per pulse did not
affect pain. * Patients with lower BMI and larger nodules had less pain.
PMID- 29330632
TI - Inate immunity in rosacea. Langerhans cells, plasmacytoid dentritic cells, Toll
like receptors and inducible oxide nitric synthase (iNOS) expression in skin
specimens: case-control study.
AB - Rosacea is a chronic inflammatory condition with predominant facial involvement.
Because of that, many patients sense that rosacea affects quality of life. The
etiology of rosacea remains unknown. Recent studies have suggested that aberrant
innate immunity is central to this disease. The aim of this study was to examine
the presence of Langerhans cells, plasmacytoid dentritic cells (PDC), the
expression of Toll-like receptors (TLR) and inducible oxide nitric synthase
(iNOS) in skin of patients with rosacea, to highlight the participation of innate
immunity in its pathogenesis. 28 biopsy specimens were taken from patients with
clinical and histopathological findings of rosacea. Immunohistochemical
demonstration of Langerhans cells (anti-CD1a antibody), PDC (anti-CD 123
antibody), TLR2, TLR4 and iNOS was performed in skin samples and compared with
normal skin controls. The expression of Langerhans cells was lower in rosacea
group than in control group. PDC were found in skin samples of rosacea as
isolated cells and forming small clusters. Expression of TLR2, TLR4 and iNOS was
higher in rosacea samples than in normal skin controls. This research
demonstrates early and late stage components of innate immunity in specimens of
rosacea ratifying the existence of an altered innate immunity in its
pathogenesis.
PMID- 29330631
TI - Apparent diffusion coefficient mapping using diffusion-weighted MRI: impact of
background parenchymal enhancement, amount of fibroglandular tissue and
menopausal status on breast cancer diagnosis.
AB - OBJECTIVES: To investigate the impact of background parenchymal enhancement
(BPE), amount of fibroglandular tissue (FGT) and menopausal status on apparent
diffusion coefficient (ADC) values in differentiation between malignant and
benign lesions. METHODS: In this HIPAA-compliant study, mean ADC values of 218
malignant and 130 benign lesions from 288 patients were retrospectively
evaluated. The differences in mean ADC values between benign and malignant
lesions were calculated within groups stratified by BPE level (high/low), amount
of FGT (dense/non-dense) and menopausal status (premenopausal/postmenopausal).
Sensitivities and specificities for distinguishing malignant from benign lesions
within different groups were compared for statistical significance. RESULTS: The
mean ADC value for malignant lesions was significantly lower compared to that for
benign lesions (1.07+/-0.21 x 10-3 mm2/s vs. 1.53+/-0.26 x 10-3 mm2/s)
(p<0.0001). Using the optimal cut-off point of 1.30 x 10-3 mm2/s, an area under
the curve of 0.918 was obtained, with sensitivity and specificity both of 87 %.
There was no statistically significant difference in sensitivities and
specificities of ADC values between different groups stratified by BPE level,
amount of FGT or menopausal status. CONCLUSIONS: Differentiation between benign
and malignant lesions on ADC values is not significantly affected by BPE level,
amount of FGT or menopausal status. KEY POINTS: * ADC allows differentiation
between benign and malignant lesions. * ADC is useful for breast cancer diagnosis
despite different patient characteristics. * BPE, FGT or menopause do not
significantly affect sensitivity and specificity.
PMID- 29330633
TI - A seven-center examination of the relationship between monthly volume and
mortality in trauma: a hypothesis-generating study.
AB - INTRODUCTION: The relationship between trauma volumes and patient outcomes
continues to be controversial, with limited data available regarding the effect
of month-to-month trauma volume variability on clinical results. This study
examines the relationship between monthly trauma volume variations and patient
mortality at seven Level I Trauma Centers located in the Eastern United States.
We hypothesized that higher monthly trauma volumes may be associated with lower
corresponding mortality. METHODS: Monthly patient volume data were collected from
seven Level I Trauma Centers. Additional information retrieved included monthly
mortality, demographics, mean monthly injury severity (ISS), and trauma mechanism
(blunt versus penetrating). Mortality was utilized as the primary study outcome.
Statistical corrections for mean age, gender distribution, ISS, and mechanism of
injury were made using analysis of co-variance (ANCOVA). Center-specific,
annually-adjusted median monthly volumes (CSAA-MMV) were calculated to
standardize patient volume differences across participating institutions.
Statistical significance was set at alpha < 0.05. RESULTS: A total of 604 months
of trauma admissions, encompassing 122,197 patients, were analyzed. Controlling
for patient age, gender, ISS, and mechanism of injury, aggregate data suggested
that monthly trauma volumes < 100 were associated with significantly greater
mortality (3.9%) than months with volumes > 400 (mortality 2.9%, p < 0.01). To
account for differences in monthly volumes between centers, as well as for
temporal bias associated with potential differences over the entire study
duration period, data were normalized using CSAA-MMV as a standardized reference
point. Monthly volumes <= 33% of the CSAA-MMV were associated with adjusted
mortality of 5.0% whereas monthly volumes >= 134% CSAA-MMV were associated with
adjusted mortality of 2.7% (p < 0.01). CONCLUSIONS: This hypothesis-generating
study suggests that greater monthly trauma volumes appear to be associated with
lower mortality. In addition, our data also suggest that across all participating
centers mortality may be a function of relative month-to-month volume variation.
When normalized to institution-specific, annually-adjusted "median" monthly
trauma contacts, we show that months with patient volumes <= 33% median may be
associated with subtly but not negligibly (1.4-2.3%) higher mortality than months
with patient volumes >= 134% median.
PMID- 29330634
TI - Corrective osteotomies using patient-specific 3D-printed guides: a critical
appraisal.
AB - INTRODUCTION: Over the last decade, the technique of 3D planning has found its
way into trauma surgery. The use of this technique in corrective osteotomies for
treatment of malunions provides the trauma surgeon with a powerful tool. However,
this technique is not entirely straightforward. We aimed to define potential
pitfalls of this technique and possible solutions to overcome these shortcomings.
MATERIALS AND METHODS: Ten patients with either a uni-, bi- or triplanar malunion
of the long bones were included in this study. These patients were divided into
three groups: a weight-bearing group and a non-weight-bearing group, the latter
was divided into the humerus group and the forearm group, subsequently. 2D
correction parameters were defined and compared within every group, as well as
the interpretations of 3D visualization. RESULTS: The weight-bearing group
revealed an undercorrection for almost all clinical measurements of the femur and
tibia, while there was adequate matching of the osteotomies and of screw entry
points in all cases. In the humerus group, coronal correction angles were nearly
perfect in all cases, while axial and sagittal correction rates, however,
differed substantially. Screw entry points and osteotomies were all at the level
as planned. The forearm group showed undercorrection in multiple planes while
there were good matching entry points for the screw trajectories. DISCUSSION:
Four major pitfalls were encountered using the 3D printing technique: (1) careful
examination of the planned guide positioning is mandatory, since suboptimal intra
operative guide positioning is most likely the main cause of the incomplete
correction; (2) the use of pre-drilled screw holes do not guarantee adequate
screw positioning; (3) translation of bone fragments over the osteotomy planes in
case of an oblique osteotomy is a potential hazard; (4) the depth of the
osteotomy is hard to estimate, potentially leading to extensive cartilage damage.
PMID- 29330635
TI - Hypotension due to spinal anesthesia influences fetal circulation in primary
caesarean sections.
AB - PURPOSE: Hypotension due to spinal anesthesia is a well-known side effect in
pregnant women receiving caesarean section. Little is known about its impact on
fetal blood circulation. METHODS: 40 women with uncomplicated singleton term
pregnancies prepared for caesarean section were prospectively evaluated by
Doppler sonography before and immediately after spinal anesthesia. RESULTS: In
90% of the women, blood pressure significantly decreased after spinal anesthesia
and 42.5% of the patients suffered from severe hypotension. We found a
significant negative correlation between maternal blood pressure change and the
resistant index (RI) of the umbilical artery (rs = - 0.376, p = 0.017) and a
significant positive correlation between maternal blood pressure and fetal middle
cerebral artery. CONCLUSION: Healthy fetuses seem to compensate well in
situations with decreased uteroplacental blood flow due to maternal hypotension
measured by means of RI changes in the fetal umbilical and middle cerebral
artery. This raises the question if growth-restricted and/or preterm fetuses are
able to compensate similarly or if general anesthesia would be a method of
choice.
PMID- 29330636
TI - A randomised trial comparing the pharmacokinetics and safety of the biosimilar CT
P6 with reference trastuzumab.
AB - PURPOSE: Access to trastuzumab, a valuable anti-cancer treatment, can be limited
by cost. The primary aim of this study was to evaluate and compare the PK
profiles of CT-P6, a biosimilar of trastuzumab, and US-licensed reference
trastuzumab (Herceptin(r)) in healthy subjects. Secondary study aims included
comparison of the safety and immunogenicity of CT-P6 and reference trastuzumab in
these subjects. METHODS: We performed a single-dose, randomised, double-blind,
parallel group study (NCT02665637) comparing CT-P6 with reference trastuzumab (6
mg/kg, 90 min intravenous infusion) in 70 healthy adult males. Pharmacokinetics,
safety and immunogenicity were evaluated up to 10 weeks post-dose. Primary
endpoints were area under the serum concentration-time curve (AUC) from time 0 to
infinity (AUCinf); AUC from time 0 to last quantifiable concentration (AUClast);
and observed maximum serum concentration (Cmax). The pre-determined equivalence
criterion was a 90% confidence interval of 80-125% for ratios of geometric least
squares (LS) means. RESULTS: Equivalence of CT-P6 and reference trastuzumab was
demonstrated. Ratios (CT-P6/reference trastuzumab) of geometric LS means (90%
confidence interval) were: AUCinf 99.05 (93.00, 105.51); AUClast 99.30 (92.85,
106.20); Cmax 96.58 (90.93, 102.59). Safety profiles were similar; treatment
emergent adverse events occurred in ten subjects (28.6%) in the CT-P6 group and
11 (31.4%) in the reference trastuzumab group. No serious adverse events or
deaths occurred. No subjects tested positive for anti-drug antibodies.
CONCLUSIONS: These data add to the totality of evidence required to demonstrate
biosimilarity. A phase III study of CT-P6-in which equivalent neoadjuvant
efficacy to reference trastuzumab has been demonstrated-is ongoing.
PMID- 29330637
TI - Assessment of the permeability properties of cryopreservation outer bags used in
NHSBT.
AB - This study was carried out to investigate leakage/transport across the bag
material of six outer cryopreservation bags in common use within NHS Blood and
Transplant. In order to do this two different leak testing procedures; coloured
dye and hydrogen tracer gas, were used. The data obtained show that a coloured
dye cannot permeate through the materials both at room temperature and following
storage at liquid nitrogen temperature (- 196 degrees C). In addition, when
filled with the smallest elemental molecule, hydrogen, in the form of a tracer
gas, all of the bags only allowed trace amounts of hydrogen to escape, either
through the seal or the bag material. The data indicated that each of the bag
materials tested would be capable of preventing bacterial or viral cross
contamination as long as the material remained intact.
PMID- 29330638
TI - Predictors of severe postoperative hyperglycemia after cardiac surgery in
infants: a single-center, retrospective, observational study.
AB - PURPOSE: Hyperglycemia is a common issue in infants after cardiac surgery for
congenital heart disease. Poor glycemic control is suspected to be associated
with adverse postoperative outcomes. This study was performed to investigate
clinical factors contributing to hyperglycemia in the perioperative period in
infats. METHODS: A total of 69 infants (aged 1-12 months) who were admitted to
Yokohama City University Hospital Intensive Care Unit (ICU) after surgical repair
of congenital heart diseases with cardiopulmonary bypass (CPB) were
retrospectively analysed. Hyperglycemia was defined as blood glucose >= 250 mg/dL
on ICU admission. Clinical background, operative factors, and postoperative
factors were compared between the hyperglycemic and non-hyperglycemic groups.
Additionally, multivariate analysis was performed to identify factors
contributing to hyperglycemia. RESULTS: Nineteen (27.5%) and 50 (72.5%) infants
were classified into the hyperglycemic and non-hyperglycemic groups,
respectively. Hyperglycemic infants were significantly younger, shorter, and
weighed less, with a higher rate of chromosomal abnormalities. Intraoperatively,
they also experienced longer CPB and surgery times and had higher peak lactate
levels and higher inotropic requirements. Hyperglycemia was related to longer
mechanical ventilation and longer ICU stays. Multivariate analysis detected
intraoperative hyperglycemia, longer CPB time, younger age and chromosomal
abnormality as significant factors. CONCLUSION: Adding to hyperglycemia during
the operation, longer CPB time younger age and chromosomal abnormality were
identified as predictors of high blood glucose levels at ICU admission.
PMID- 29330639
TI - Changes in tissue and cerebral oxygenation following spinal anesthesia in
infants: a prospective study.
AB - Use of spinal anesthesia (SA) in children may address concerns about potential
neurocognitive effects of general anesthesia. We used near-infrared spectroscopy
(NIRS) to assess the effects of SA on cerebral and tissue oxygenation in 19
patients aged 7 +/- 3 months. Prior to SA placement, NIRS monitors were placed on
the forehead (cerebral) and the thigh (tissue). Intraoperative cerebral and
tissue saturation were 73 +/- 7 and 80 +/- 11%, respectively, before SA
placement. NIRS measurements were monitored every minute for 30 min after SA
placement and modeled using mixed-effects linear regression. Regression estimates
showed that cerebral saturation remained stable from 67% [95% confidence interval
(CI) 63, 71%] after SA placement to 68% (95% CI 65, 72%) at the conclusion of
monitoring. After SA placement, tissue saturation was elevated compared to
baseline values; but further change [from 91% (95% CI 89, 93%) to 93% (95% CI 91,
95%) at the end of monitoring] was clinically non-significant. All patients
breathed spontaneously on room air without changes in oxygen saturation. Blood
pressure and heart rate decreased after SA placement, but no changes in
hemodynamic parameters required treatment. These data provide further evidence of
the neutral effect of SA on cerebral oxygenation 30 min after block placement.
PMID- 29330640
TI - Is Contact with Children Related to Legitimizing Beliefs Toward Sex with Children
Among Men with Pedophilia?
AB - Among pedophilic men, social contact with children has been discussed as creating
a risk situation for sexual abuse. Also, pedophilic men searching for such
contact are seen as harboring more beliefs legitimizing sexual contact with
children. However, social contact may also decrease false beliefs. We tested
these competing views in an anonymous Internet survey with a non-forensic, non
clinical sample of 104 self-classified pedophilic men. Results showed that both
increased social and physical contact were significantly linked to fewer
legitimizing beliefs toward sex with children, even when controlling for past
psychotherapy, educational level, social desirability, and age. Controlling for
previous conviction for child sexual offenses reduced the effect for physical
contact, but not for social contact. Exploratory analyses showed that either type
of contact had no significant effect on total self-perceived risk of offending.
However, pedophilic men with physical contact with children perceived a higher
risk of more direct (i.e., child abuse) than indirect offenses (i.e., child
pornography offenses) compared to pedophilic men without physical contact.
Despite limitations of the correlational design and the only small to moderate
effects, the results challenge the assumption that complete avoidance of contact
with children is necessary for persons with pedophilia to reduce the risk of
abusive behavior.
PMID- 29330641
TI - Characteristics of MUTYH variants in Japanese colorectal polyposis patients.
AB - BACKGROUND: The base excision repair gene MUTYH is the causative gene of
colorectal polyposis syndrome, which is an autosomal recessive disorder
associated with a high risk of colorectal cancer. Since few studies have
investigated the genotype-phenotype association in Japanese patients with MUTYH
variants, the aim of this study was to clarify the clinicopathological findings
in Japanese patients with MUTYH gene variants who were detected by screening
causative genes associated with hereditary colorectal polyposis. METHODS: After
obtaining informed consent, genetic testing was performed using target enrichment
sequencing of 26 genes, including MUTYH. RESULTS: Of the 31 Japanese patients
with suspected hereditary colorectal polyposis, eight MUTYH variants were
detected in five patients. MUTYH hotspot variants known for Caucasians, namely
p.G396D and p.Y179D, were not among the detected variants.Of five patients, two
with biallelic MUTYH variants were diagnosed with MUTYH-associated polyposis,
while two others had monoallelic MUTYH variants. One patient had the p.P18L and
p.G25D variants on the same allele; however, supportive data for considering
these two variants 'pathogenic' were lacking. CONCLUSIONS: Two patients with
biallelic MUTYH variants and two others with monoallelic MUTYH variants were
identified among Japanese colorectal polyposis patients. Hotspot variants of the
MUTYH gene for Caucasians were not hotspots for Japanese patients.
PMID- 29330642
TI - Meta-analysis of randomized clinical trials in the era of individual patient data
sharing.
AB - BACKGROUND: Individual patient data (IPD) meta-analysis is considered to be a
gold standard when the results of several randomized trials are combined. Recent
initiatives on sharing IPD from clinical trials offer unprecedented opportunities
for using such data in IPD meta-analyses. METHODS: First, we discuss the evidence
generated and the benefits obtained by a long-established prospective IPD meta
analysis in early breast cancer. Next, we discuss a data-sharing system that has
been adopted by several pharmaceutical sponsors. We review a number of
retrospective IPD meta-analyses that have already been proposed using this data
sharing system. Finally, we discuss the role of data sharing in IPD meta-analysis
in the future. RESULTS: Treatment effects can be more reliably estimated in both
types of IPD meta-analyses than with summary statistics extracted from published
papers. Specifically, with rich covariate information available on each patient,
prognostic and predictive factors can be identified or confirmed. Also, when
several endpoints are available, surrogate endpoints can be assessed
statistically. CONCLUSIONS: Although there are difficulties in conducting,
analyzing, and interpreting retrospective IPD meta-analysis utilizing the
currently available data-sharing systems, data sharing will play an important
role in IPD meta-analysis in the future.
PMID- 29330643
TI - Antihypertensive Medication and Dementia Risk in Older Adult African Americans
with Hypertension: A Prospective Cohort Study.
AB - BACKGROUND: African Americans are especially at risk of hypertension and
dementia. Antihypertensive medications reduce the risk of cardiovascular events,
but may also reduce the risk of dementia. OBJECTIVE: To assess the longitudinal
effects of antihypertensive medications and blood pressure on the onset of
incident dementia in a cohort of African Americans. DESIGN: Prospective cohort.
PARTICIPANTS: 1236 community-dwelling patients from an inner-city public health
care system, aged 65 years and older, with a history of hypertension but no
history of dementia, and who had at least three primary care visits and a
prescription filled for any medication. MAIN MEASURES: Blood pressure was the
average of three seated measurements. Dementia was diagnosed using a two-stage
design, with a screening evaluation every 2 to 3 years followed by a
comprehensive in-home clinical evaluation for those with a positive screen.
Laboratory, inpatient and outpatient encounter data, coded diagnoses and
procedures, and medication records were derived from a health information
exchange. KEY RESULTS: Of the 1236 hypertensive participants without dementia at
baseline, 114 (9%) developed incident dementia during follow-up. Individuals
prescribed any antihypertensive medication (n = 816) were found to have a
significantly reduced risk of dementia (HR = 0.57, 95% CI 0.37-0.88, p = 0.0114)
compared to untreated hypertensive participants (n = 420). When this analysis was
repeated including a variable indicating suboptimally treated blood pressure (>
140 mmHg systolic or >90 mmHg diastolic), the effect of antihypertensive
medication was no longer statistically significant (HR = 0.65, 95% CI 0.32-1.30,
p = 0.2217). CONCLUSIONS: Control of blood pressure in older adult African
American patients with hypertension is a key intervention for preventing
dementia, with similar benefits from most of the commonly available
antihypertensive medications.
PMID- 29330644
TI - Hydrocarbon Stapled Antimicrobial Peptides.
AB - Antimicrobial peptides are promising candidates for anti-infective
pharmaceuticals. Unfortunately, because of their low proteolytic and chemical
stability, their usage is generally narrowed down to topical formulations. Until
now, numerous approaches to increase peptide stability have been proposed. One of
them, peptide hydrocarbon stapling, a modification based on stabilizing peptide
secondary structure with a side-chain covalent hydrocarbon bridge, have been
successfully applied to many peptides. Moreover, constraining secondary structure
of peptides have also been proven to increase their biological activity. This
review article describes studies on hydrocarbon stapled antimicrobial peptides
with respect to improved drug-like properties.
PMID- 29330645
TI - Delayed leptomeningeal metastasis of an adult anaplastic pilocytic astrocytoma.
PMID- 29330646
TI - Potential impact of SGLT2 inhibitors on left ventricular diastolic function in
patients with diabetes mellitus.
AB - The pathogenesis of diabetes mellitus (DM)-related cardiac dysfunction is thought
to be multifactorial, and possibly a key factor for the development of heart
failure with preserved ejection fraction (HFpEF) in patients with DM and
preserved left ventricular (LV) ejection fraction. Currently, there is no
effective treatment for HFpEF, which is presented as LV diastolic dysfunction.
Furthermore, it is well known that, in addition to DM, hypertension and
overweight/obesity are also important factors associated with HFpEF. Sodium
glucose cotransporter 2 (SGLT2) inhibitors are a new class of diabetic
medications indicated only for the treatment of type 2 DM, and a recent clinical
trial showed that patients with this disease and at high risk for cardiovascular
events attained cardiovascular benefits from SGLT2 inhibitor in comparison with
placebo efficacy. In addition to reduction of glycated hemoglobin levels in
patients with type 2 DM, SGLT2 inhibitors are associated with weight loss and
reductions in blood pressure. However, despite such intriguing results, it
remains uncertain whether SGLT2 inhibitors are beneficial for LV diastolic
function in patients with DM. This review deals with the impact of SGLT2
inhibitors on LV diastolic function in patients with DM and their current
potential for prevention of the future development of HFpEF in such patients.
PMID- 29330647
TI - Absence of the Nitrous Oxide Reductase Gene Cluster in Commercial Alfalfa
Inoculants Is Probably Due to the Extensive Loss of Genes During Rhizobial
Domestication.
AB - As other legume crops, alfalfa cultivation increases the emission of the
greenhouse gas nitrous oxide (N2O). Since legume-symbiotic nitrogen-fixing
bacteria play a crucial role in this emission, it is important to understand the
possible impacts of rhizobial domestication on the evolution of denitrification
genes. In comparison with the genomes of non-commercial strains, those of
commercial alfalfa inoculants exhibit low total genome size, low number of ORFs
and high numbers of both frameshifted genes and pseudogenes, suggesting a
dramatic loss of genes during bacterial domestication. Genomic analysis focused
on denitrification genes revealed that commercial strains have perfectly
conserved the nitrate (NAP), nitrite (NIR) and nitric (NOR) reductase clusters
related to the production of N2O from nitrate but completely lost the nitrous
oxide (NOS) reductase cluster (nosRZDFYLX genes) associated with the reduction of
N2O to gas nitrogen. Based on these results, we propose future screenings for
alfalfa-nodulating isolates containing both nitrogen fixation and N2O reductase
genes for environmental sustainability of alfalfa production.
PMID- 29330648
TI - Cloning, expression and characterization of the esterase estUT1 from Ureibacillus
thermosphaericus which belongs to a new lipase family XVIII.
AB - A new esterase gene from thermophilic bacteria Ureibacillus thermosphaericus was
cloned into the pET32b vector and expressed in Escherichia coli BL21(DE3).
Alignment of the estUT1 amino acid sequence revealed the presence of a novel
canonical pentapeptide (GVSLG) and 41-47% identity to the closest family of the
bacterial lipases XIII. Thus the esterase estUT1 from U. thermosphaericus was
assigned as a member of the novel family XVIII. It also showed a strong activity
toward short-chain esters (C2-C8), with the highest activity for C2. When p
nitrophenyl butyrate is used as a substrate, the temperature and pH optimum of
the enzyme were 70-80 degrees C and 8.0, respectively. EstUT1 showed high
thermostability and 68.9 +/- 2.5% residual activity after incubation at 70
degrees C for 6 h. Homology modeling of the enzyme structure showed the presence
of a putative catalytic triad Ser93, Asp192, and His222. The activity of estUT1
was inhibited by PMSF, suggesting that the serine residue is involved in the
catalytic activity of the enzyme. The purified enzyme exhibited high stability in
organic solvents. EstUT1 retained 85.8 +/- 2.4% residual activity in 30% methanol
at 50 degrees C for 6 h. Stability at high temperature and tolerance to organic
solvents make estUT1 a promising enzyme for biotechnology application.
PMID- 29330649
TI - Growth of Leptospirillum ferriphilum in sulfur medium in co-culture with
Acidithiobacillus caldus.
AB - Leptospirillum ferriphilum and Acidithiobacillus caldus are both thermotolerant
acidophilic bacteria that frequently co-exist in natural and man-made
environments, such as biomining sites. Both are aerobic chemolithotrophs; L.
ferriphilum is known only to use ferrous iron as electron donor, while A. caldus
can use zero-valent and reduced sulfur, and also hydrogen, as electron donors. It
has recently been demonstrated that A. caldus reduces ferric iron to ferrous when
grown aerobically on sulfur. Experiments were carried out which demonstrated that
this allowed L. ferriphilum to be sustained for protracted periods in media
containing very little soluble iron, implying that dynamic cycling of iron
occurred in aerobic mixed cultures of these two bacteria. In contrast, numbers of
viable L. ferriphilum rapidly declined in mixed cultures that did not contain
sulfur. Data also indicated that growth of A. caldus was partially inhibited in
the presence of L. ferriphilum. This was shown to be due to greater sensitivity
of the sulfur-oxidizer to ferric than to ferrous iron, and to highly positive
redox potentials, which are characteristic of cultures containing Leptospirillum
spp. The implications of these results in the microbial ecology of extremely
acidic environments and in commercial bioprocessing applications are discussed.
PMID- 29330650
TI - A cold-adapted endoglucanase from camel rumen with high catalytic activity at
moderate and low temperatures: an anomaly of truly cold-adapted evolution in a
mesophilic environment.
AB - Endoglucanases are important enzymes in plant biomass degradation. They have
current and potential applications in various industrial sectors including human
and animal food processing, textile, paper, and renewable biofuel production. It
is assumed that the cold-active endoglucanases, with high catalytic rates in
moderate and cold temperatures, can improve the cost-effectiveness of industrial
processes by lowering the need for heating and, thus, energy consumption. In this
study, the endoglucanase CelCM3 was procured from a camel rumen metagenome via
gene cloning and expression in Escherichia coli BL21 (DE3). The maximum activity
of the enzyme on carboxymethyl cellulose (CMC) was obtained at pH 5 and 30
degrees C with a Vmax and Km of 339 U/mg and 2.57 mg/ml, respectively. The enzyme
with an estimated low melting temperature of 45 degrees C and about 50% activity
at 4 degrees C was identified to be cold-adapted. A thermodynamic analysis
corroborated that CelCM3 with an activation energy (Ea), enthalpy of activation
(DeltaH), and Gibb's free energy (DeltaG) of, respectively, 18.47 kJ mol-1, 16.12
kJ mol-1, and 56.09 kJ mol-1 is a cold-active endoglucanase. In addition, CelCM3
was tolerant of metal ions, non-ionic detergents, urea, and organic solvents.
Given these interesting characteristics, CelCM3 shows promise to meet the
requirements of industrial applications.
PMID- 29330651
TI - 3D-computed tomography to compare the dimensions of the left atrial appendage in
patients with normal sinus rhythm and those with paroxysmal atrial fibrillation.
AB - Although paroxysmal atrial fibrillation (PAF) is an important cause of
cardioembolic stroke, in contrast to chronic AF patients, the anatomical features
of the left atrial appendage (LAA) in PAF patients remain unknown. Here, we
investigated differences in LAA structures in patients with PAF and those with
normal sinus rhythms (NSR) using 3D-computed tomography (3D-CT), which allows us
to visualize complicated LAA structures at high spatial resolution. Study
subjects were 30 consecutive PAF and 30 NSR patients with complete enhanced
cardiac 3D-CT images available. After reconstruction of 3D LAA images, anatomical
parameters of the LAA were measured and compared according to three proposed
definitions of the LAA orifice plane determined by the following anatomical
landmarks: DEF#1, center of warfarin ridge and centerline of proximal left
circumflex artery; DEF#2, slope of warfarin ridge and mitral valve annulus;
DEF#3, observers' discretion by progressive rotation using the observers' best
estimate without the use of landmarks. The LAA volumes of the PAF groups were
significantly greater than the NSR group according to all 3 definitions (DEF#1:
1.43 times, DEF#2: 1.44 times, and DEF#3: 1.36 times greater). The LAA orifice
area was significantly larger in PAF than in NSR according to DEF#2, but was
similar by DEF#1 and DEF#3. Intra-observer and inter-observer variations for any
LAA measurements were very low. In conclusion, 3D-CT-based quantitative
assessment of the LAA provides highly reproducible and detailed measurements,
which can successfully discriminate differences of LAA volume between patients
with NSR and those with PAF, suggesting significantly greater volumes in the
latter.
PMID- 29330653
TI - Aurora D. Pryor, M.D.
PMID- 29330652
TI - Dietary Management in the Immediate Preoperative Period of Bariatric Surgery: a
National Overview : Bariatric Preoperative Diets.
AB - BACKGROUND: Although widely applied, there is no consensus about the
characteristics of the diets prescribed in the immediate preoperative period of
bariatric surgery (BS). The objective of this study was to perform a survey on
preoperative dietary management in BS centers. METHODS: This was a cross
sectional study with BS Brazilian centers. Only BS centers with certificate of
excellence by Surgical Review Corporation were included. An electronic
questionnaire was applied to assess details about the dietary management in the
immediate preoperative period of BS. RESULTS: Of the 15 centers invited, 80% (n =
12) answered the questionnaire. Preoperative weight loss was required to patients
in all 12 centers. For 8.3% (n = 1), this request was applied to all patients;
91.7% (n = 11) of the centers requested weight loss in specific cases. Ten
(83.3%) centers prescribed restrictive diets; none of these adopted a standard
dietary protocol. The caloric value of the diets ranged from 800 to 2000
kcal/day. The duration of the diet ranged from 10 to 20 days in 40% (n = 4) of
the centers and from 20 to 90 days in 60% (n = 6) of the centers. Dietary
prescription was based on team consensus in 100% (n = 12) of the centers. In
33.3% (n = 4) of the centers, scientific evidence supporting dietary prescription
was cited. CONCLUSION: This study identified the frequent practice of requesting
preoperative weight loss and the diversity of diets used in the immediate
preoperative period by Brazilian BS centers. Future guideline proposal is needed
on preoperative BS diets.
PMID- 29330654
TI - Risk Prediction Model for Severe Postoperative Complication in Bariatric Surgery.
AB - BACKGROUND: Factors associated with risk for adverse outcome are important
considerations in the preoperative assessment of patients for bariatric surgery.
As yet, prediction models based on preoperative risk factors have not been able
to predict adverse outcome sufficiently. OBJECTIVE: This study aimed to identify
preoperative risk factors and to construct a risk prediction model based on
these. METHODS: Patients who underwent a bariatric surgical procedure in Sweden
between 2010 and 2014 were identified from the Scandinavian Obesity Surgery
Registry (SOReg). Associations between preoperative potential risk factors and
severe postoperative complications were analysed using a logistic regression
model. A multivariate model for risk prediction was created and validated in the
SOReg for patients who underwent bariatric surgery in Sweden, 2015. RESULTS:
Revision surgery (standardized OR 1.19, 95% confidence interval (CI) 1.14-0.24, p
< 0.001), age (standardized OR 1.10, 95%CI 1.03-1.17, p = 0.007), low body mass
index (standardized OR 0.89, 95%CI 0.82-0.98, p = 0.012), operation year
(standardized OR 0.91, 95%CI 0.85-0.97, p = 0.003), waist circumference
(standardized OR 1.09, 95%CI 1.00-1.19, p = 0.059), and dyspepsia/GERD
(standardized OR 1.08, 95%CI 1.02-1.15, p = 0.007) were all associated with risk
for severe postoperative complication and were included in the risk prediction
model. Despite high specificity, the sensitivity of the model was low.
CONCLUSION: Revision surgery, high age, low BMI, large waist circumference, and
dyspepsia/GERD were associated with an increased risk for severe postoperative
complication. The prediction model based on these factors, however, had a
sensitivity that was too low to predict risk in the individual patient case.
PMID- 29330655
TI - Effectiveness for dentin hypersensitivity treatment of non-carious cervical
lesions: a meta-analysis.
AB - OBJECTIVE: The aim of this review is to conduct a systematic review and meta
analysis comparing the effectiveness of in-home or in-office treatments for
dentin hypersensitivity. MATERIALS AND METHODS: An electronic search without
restriction on dates or languages was performed in four electronic databases
until March 2017. In addition, hand-searches in regular journals and in the gray
literature were also conducted. To develop the search strategy, clinical
questions were formulated using the PICOS method. Eligibility criteria included
randomized clinical trials (RCTs) that compared the effectiveness of different
agents for the treatment of dentin hypersensitivity through chemical occlusion,
physical occlusion, nerve desensitization, or photobiomodulation (low-level light
therapy). This systematic review was registered in PROSPERO under number
CRD42016039394. RESULTS: Twenty-five RCTs (16 parallel; 9 split-mouth), published
from 1992 to 2016, were included. The results of the meta-analysis showed that in
office subgroups treated with chemical or physical occlusion of dentin tubules
and nerve desensitization had a statistically significant difference from
placebo, with P < 0.00001, P < 0.00001, and P = 0.02, respectively. For in-home
treatments, the results of the meta-analysis showed that only those subgroups
treated with chemical occlusion of dentin tubules and nerve desensitization
exhibited a statistically significant difference from placebo, with P < 0.00001
and P = 0.03, respectively. CONCLUSIONS: The results of pairwise meta-analysis
suggest that among in-office treatments, dentinal tubule occlusion (whether
chemical or physical) and nerve desensitization provide the best outcomes for
treatment of dentin hypersensitivity. For in-home treatments, only chemical
occlusion of dentin tubules and nerve desensitization showed a greater treatment
efficacy than placebo and the difference was statistically significant.
PMID- 29330657
TI - The T1 shine through effect on susceptibility weighted imaging: an under
recognized phenomenon.
PMID- 29330656
TI - 3D imaging, 3D printing and 3D virtual planning in endodontics.
AB - The adoption and adaptation of recent advances in digital technology, such as
three-dimensional (3D) printed objects and haptic simulators, in dentistry have
influenced teaching and/or management of cases involving implant, craniofacial,
maxillofacial, orthognathic and periodontal treatments. 3D printed models and
guides may help operators plan and tackle complicated non-surgical and surgical
endodontic treatment and may aid skill acquisition. Haptic simulators may assist
in the development of competency in endodontic procedures through the acquisition
of psycho-motor skills. This review explores and discusses the potential
applications of 3D printed models and guides, and haptic simulators in the
teaching and management of endodontic procedures. An understanding of the
pertinent technology related to the production of 3D printed objects and the
operation of haptic simulators are also presented.
PMID- 29330658
TI - Patient-specific model-based segmentation of brain tumors in 3D intraoperative
ultrasound images.
AB - PURPOSE: Intraoperative ultrasound (iUS) imaging is commonly used to support
brain tumor operation. The tumor segmentation in the iUS images is a difficult
task and still under improvement because of the low signal-to-noise ratio. The
success of automatic methods is also limited due to the high noise sensibility.
Therefore, an alternative brain tumor segmentation method in 3D-iUS data using a
tumor model obtained from magnetic resonance (MR) data for local MR-iUS
registration is presented in this paper. The aim is to enhance the visualization
of the brain tumor contours in iUS. METHODS: A multistep approach is proposed.
First, a region of interest (ROI) based on the specific patient tumor model is
defined. Second, hyperechogenic structures, mainly tumor tissues, are extracted
from the ROI of both modalities by using automatic thresholding techniques.
Third, the registration is performed over the extracted binary sub-volumes using
a similarity measure based on gradient values, and rigid and affine
transformations. Finally, the tumor model is aligned with the 3D-iUS data, and
its contours are represented. RESULTS: Experiments were successfully conducted on
a dataset of 33 patients. The method was evaluated by comparing the tumor
segmentation with expert manual delineations using two binary metrics: contour
mean distance and Dice index. The proposed segmentation method using local and
binary registration was compared with two grayscale-based approaches. The
outcomes showed that our approach reached better results in terms of
computational time and accuracy than the comparative methods. CONCLUSION: The
proposed approach requires limited interaction and reduced computation time,
making it relevant for intraoperative use. Experimental results and evaluations
were performed offline. The developed tool could be useful for brain tumor
resection supporting neurosurgeons to improve tumor border visualization in the
iUS volumes.
PMID- 29330659
TI - Coffee with a high content of chlorogenic acids and low content of
hydroxyhydroquinone improves postprandial endothelial dysfunction in patients
with borderline and stage 1 hypertension.
AB - PURPOSE: The purpose of this study was to evaluate acute effects of coffee with a
high content of chlorogenic acids and different hydroxyhydroquinone contents on
postprandial endothelial dysfunction. METHODS: This was a single-blind,
randomized, placebo-controlled, crossover-within-subject clinical trial. A total
of 37 patients with borderline or stage 1 hypertension were randomized to two
study groups. The participants consumed a test meal with a single intake of the
test coffee. Subjects in the Study 1 group were randomized to single intake of
coffee with a high content of chlorogenic acids and low content of
hydroxyhydroquinone or coffee with a high content of chlorogenic acids and a high
content of hydroxyhydroquinone with crossover. Subjects in the Study 2 group were
randomized to single intake of coffee with a high content of chlorogenic acids
and low content of hydroxyhydroquinone or placebo coffee with crossover.
Endothelial function assessed by flow-mediated vasodilation and plasma
concentration of 8-isoprostanes were measured at baseline and at 1 and 2 h after
coffee intake. RESULTS: Compared with baseline values, single intake of coffee
with a high content of chlorogenic acids and low content of hydroxyhydroquinone,
but not coffee with a high content of chlorogenic acids and high content of
hydroxyhydroquinone or placebo coffee, significantly improved postprandial flow
mediated vasodilation and decreased circulating 8-isoprostane levels.
CONCLUSIONS: These findings suggest that a single intake of coffee with a high
content of chlorogenic acids and low content of hydroxyhydroquinone is effective
for improving postprandial endothelial dysfunction. CLINICAL TRIAL REGISTRATION:
URL for Clinical Trial: https://upload.umin.ac.jp ; Registration Number for
Clinical Trial: UMIN000013283.
PMID- 29330660
TI - Theobromine consumption does not improve fasting and postprandial vascular
function in overweight and obese subjects.
AB - BACKGOUND: Theobromine, a component of cocoa, may favorably affect conventional
lipid-related cardiovascular risk markers, but effects on flow-mediated dilation
(FMD) and other vascular function markers are not known. OBJECTIVE: To evaluate
the effects of 4-week theobromine consumption (500 mg/day) on fasting and
postprandial vascular function markers. DESIGN: In a randomized, double-blind
crossover study, 44 apparently healthy overweight (N = 30) and obese (N = 14) men
and women with low HDL-C concentrations, consumed daily 500 mg theobromine or
placebo for 4 weeks. After 4 weeks, FMD, peripheral arterial tonometry (PAT),
augmentation index (AIx), pulse wave velocity (PWV), blood pressure (BP) and
retinal microvasculature measurements were performed. These measurements were
carried out under fasting conditions and 2.5 h after a high-fat mixed meal
challenge. RESULTS: 4-week theobromine consumption did not change fasting
vascular function markers, except for a decrease in central AIx (cAIx, - 1.7 pp,
P = 0.037) and a trend towards smaller venular calibers (- 2 um, P = 0.074).
Consuming a high-fat mixed meal decreased FMD (0.89 pp, P = 0.002), reactive
hyperemia index (RHI, - 0.30, P < 0.001), peripheral systolic BP (SBP, - 3 mmHg,
P <= 0.001), peripheral diastolic BP (DBP, - 2 mmHg, P <= 0.001), central SBP (-
6 mmHg, P <= 0.001) and central DBP (- 2 mmHg, P <= 0.001), but increased heart
rate (HR, 2 bpm, P < 0.001). Theobromine did not modify these postprandial
effects, but increased postprandially the brachial artery diameter (0.03 cm, P =
0.015), and decreased the cAIx corrected for a HR of 75 (cAIx75, - 5.0 pp, P =
0.004) and peripheral AIx (pAIx, - 6.3 pp, P = 0.017). CONCLUSION: Theobromine
consumption did not improve fasting and postprandial endothelial function, but
increased postprandial peripheral arterial diameters and decreased the AIx. These
findings do not suggest that theobromine alone contributes to the proposed
cardioprotective effects of cocoa. This trial was registered on
clinicaltrials.gov under study number NCT02209025.
PMID- 29330661
TI - Adipose tissue fatty acids present in dairy fat and risk of stroke: the Danish
Diet, Cancer and Health cohort.
AB - PURPOSE: The role of dairy fat for the risk of stroke is not yet clear. Adipose
tissue reflects long-term fatty acid intake and metabolism. We, therefore,
investigated associations for percentages of adipose tissue fatty acids, for
which dairy products are a major source (12:0, 14:0, 14:1 cis-9, 15:0, 17:0, 18:1
trans-11 and 18:2 cis-9, trans-11), with incident total stroke and stroke
subtypes. METHODS: We conducted a case-cohort study within the Danish Diet,
Cancer and Health cohort, including all incident stroke cases (n = 2108) and a
random sample of the total cohort (n = 3186). The fatty acid composition of
adipose tissue biopsies was determined by gas chromatography and specific fatty
acids were expressed as percentage of total fatty acids. Stroke cases were
identified in the Danish National Patient Registry and the diagnoses were
individually verified. RESULTS: We recorded 2108 stroke cases of which 1745 were
ischemic, 249 were intracerebral hemorrhages and 102 were subarachnoid
hemorrhages. We observed a lower rate of ischemic stroke for a higher adipose
tissue percentage of 12:0, 14:0, 15:0, 17:0, 18:1 trans-11 and 18:2 cis-9, trans
11. Adipose tissue percentages of 15:0 and 18:1 trans-11 were also inversely
associated with intracerebral hemorrhage, whereas no associations between the
adipose tissue fatty acids and subarachnoid hemorrhage were observed. No
associations between 14:1 cis-9 and ischemic or hemorrhagic stroke were found.
CONCLUSIONS: Our results suggest that a larger percentage in adipose tissue of
fatty acids for which dairy products are a major source is associated with a
lower rate of ischemic stroke.
PMID- 29330662
TI - Yogurt consumption is associated with higher nutrient intake, diet quality and
favourable metabolic profile in children: a cross-sectional analysis using data
from years 1-4 of the National diet and Nutrition Survey, UK.
AB - PURPOSE: Yogurt consumption has been associated with higher nutrient intakes,
better diet quality and improved metabolic profiles in adults. Few studies have
investigated these associations in children. This study investigated the
association of yogurt consumption with nutrient intakes, diet quality and
metabolic profile in British children. METHODS: Data from 1687 children aged 4
10 and 11-18 years of the National Diet and Nutrition Survey (NDNS) years 1-4
were analysed. Yogurt consumption was determined using a 4-day diet diary. Diet
quality was assessed by the Healthy Eating Index 2010 (HEI-2010). Anthropometric
measures, blood pressure, pulse pressure, plasma glucose, HbA1c, C-reactive
protein, triacylglycerol, total cholesterol, high-and low-density cholesterol
from NDNS were used. RESULTS: The highest tertile of yogurt consumption (T3) was
associated with higher nutrient intakes, particularly for calcium (children 4-10
years: P < 0.0001; children 11-18 years P = 0.001), iodine (both age groups P <
0.0001) and riboflavin (both age groups P < 0.0001), and HEI-2010 score (both age
groups P < 0.0001) in children aged 4-10 years (mean +/- SD: 98.4 +/- 35.7 g
yogurt/day) and 11-18 years (mean +/- SD: 105.4 +/- 37.5 g yogurt/day) compared
with non-consumers (0 g yogurt/d). Yogurt consumption was associated with
significantly lower pulse pressure in children aged 4-10 years and lower HbA1c
concentration, being shorter and having a larger hip circumference in children
aged 11-18 years, compared with non-yogurt consumers. CONCLUSION: This study
suggests that British children who are yogurt consumers (> 60 g/day) have higher
overall diet quality, nutrient intakes and adequacy, lower pulse pressure
(children aged 4-10 years) and HbA1c concentrations (children aged 11-18 years),
were shorter and had a smaller hip circumference (children aged 11-18 years).
PMID- 29330663
TI - Human cytomegalovirus-encoded miR-UL112 contributes to HCMV-mediated vascular
diseases by inducing vascular endothelial cell dysfunction.
AB - Human cytomegalovirus (HCMV) infection has been linked to the pathogenesis of
vasculopathy by inducing dysfunction of vascular cells such as endothelial cells.
Hcmv-miR-UL112 is the most well-characterized HCMV-encoded microRNA occurring in
the plasma of patients with cardiovascular diseases such as hypertension, while
the specific underlying pathophysiological mechanisms are yet to be defined. The
current study investigated the effect of hcmv-miR-UL112 on the growth and
proliferation of human umbilical vascular endothelial cells (HUVECs); it might
also be associated with signaling pathways. An adenovirus vector was designed and
synthesized to stably express hcmv-miR-UL112 in HUVECs. Cell Counting Kit-8
results showed that ectopically expressed hcmv-miR-UL112 can significantly
increase the proliferation of HUVECs (p < 0.05). Flow cytometry revealed that the
S-phase fraction in the cell cycle analysis was raised significantly after
overexpression of hcmv-miR-UL112 (p < 0.05). Gene expression profile analysis,
using the microarray technology, revealed 303 up-regulated and 62 down-regulated
genes in HUVECs by comparing the AD-hcmv-miR-UL112-infected and control groups (p
< 0.05 and > 2 fold change). Kyoto Encyclopedia of Genes and Genomes and Reactome
Pathway, chosen as the functional annotation categories, were affected by hcmv
miR-UL112 adenovirus vector. The significantly altered pathways mainly include
the mitogen-activated protein kinase signaling pathway, cell adhesion molecules,
chemokine signaling pathway, cytokine-cytokine receptor interaction, circadian
rhythm-mammal, mineral absorption, protein processing in the endoplasmic
reticulum, proximal tubule bicarbonate reclamation, vasopressin-regulated water
reabsorption, and arachidonic acid metabolism. In conclusion, hcmv-miR-UL112
could serve as a potential biomarker, and the miRNA-mediated regulation of
signaling pathways might play significant roles in the physiological effects of
hcmv-associated diseases.
PMID- 29330664
TI - An Iranian genomic sequence of Beet mosaic virus provides insights into diversity
and evolution of the world population.
AB - Beet mosaic virus (BtMV), the only Potyvirus known to infect sugar beet, occurs
worldwide in beet crops. The full genome sequencing of a BtMV isolate from Iran
(Ir-VRU), enabled us to better understand the evolutionary history of this virus.
Selection analysis suggested that BtMV evolution is mainly under negative
selection but its strength varies in different proteins with the multifunctional
proteins under strongest selection. Recombination has played a major role in the
evolution of the BtMVs; only the Ir-VRU and USA isolates show no evidence of
recombination. The ML phylogenies of BtMVs from coat protein and full sequences
were completely congruent. The primary divergence of the BtMV phylogeny is into
USA and Eurasian lineages, and the latter then divides to form a cluster only
found in Iran, and a sister cluster that includes all the European and Chinese
isolates. A simple patristic dating method estimated that the primary divergence
of the BtMV population was only 360 (range 260-490) years ago, suggesting an
emergence during the development of sugar beet as a crop over the past three
centuries rather than with the use of leaf beet as a vegetable for at least 2000
years.
PMID- 29330665
TI - A synthetic pathway for the production of 2-hydroxyisovaleric acid in Escherichia
coli.
AB - Synthetic biology, encompassing the design and construction of novel artificial
biological pathways and organisms and the redesign of existing natural biological
systems, is rapidly expanding the number of applications for which biological
systems can play an integral role. In the context of chemical production, the
combination of synthetic biology and metabolic engineering approaches continues
to unlock the ability to biologically produce novel and complex molecules from a
variety of feedstocks. Here, we utilize a synthetic approach to design and build
a pathway to produce 2-hydroxyisovaleric acid in Escherichia coli and demonstrate
how pathway design can be supplemented with metabolic engineering approaches to
improve pathway performance from various carbon sources. Drawing inspiration from
the native pathway for the synthesis of the 5-carbon amino acid L-valine, we
exploit the decarboxylative condensation of two molecules of pyruvate, with
subsequent reduction and dehydration reactions enabling the synthesis of 2
hydroxyisovaleric acid. Key to our approach was the utilization of an
acetolactate synthase which minimized kinetic and regulatory constraints to
ensure sufficient flux entering the pathway. Critical host modifications enabling
maximum product synthesis from either glycerol or glucose were then examined,
with the varying degree of reduction of these carbons sources playing a major
role in the required host background. Through these engineering efforts, the
designed pathway produced 6.2 g/L 2-hydroxyisovaleric acid from glycerol at 58%
of maximum theoretical yield and 7.8 g/L 2-hydroxyisovaleric acid from glucose at
73% of maximum theoretical yield. These results demonstrate how the combination
of synthetic biology and metabolic engineering approaches can facilitate bio
based chemical production.
PMID- 29330666
TI - Heidegger, communication, and healthcare.
AB - Communication between medical professionals and patients is an important aspect
of therapy and patient satisfaction. Common barriers that get in the way of
effective communication in this sphere include: (1) gender, age, and cultural
differences; (2) physical or psychological discomfort or pain; (3) medical
literacy; and (4) distraction due to technological factors or simply being
overworked. The author examines these communicative barriers from a philosophical
lens and then utilizes Martin Heidegger's phenomenology and hermeneutics to
provide guidance for medical professional-patient interactions. The
phenomenological approach espoused emphasizes the particular, contextual nature
of such interactions, and thus is opposed to abstract, theoretical principles.
Heidegger's hermeneutics provides a philosophical approach to communication that
may guide the back-and-forth interpretation that should happen between medical
professionals and patients to achieve effective communication.
PMID- 29330667
TI - Diversity and Phenology of Wild Bees in a Highly Disturbed Tropical Dry Forest
"Desierto de la Tatacoa", Huila-Colombia.
AB - Colombian tropical dry forest is considered the most endangered tropical biome
due to anthropic activities. Desierto de la Tatacoa (DsT) is an example of high
disturbed tropical dry forest which still maintains a high biodiversity. The
objective of the study was to record the diversity and phenology of wild bees in
this place by monthly sampling between December 2014 and December 2016 in a 9-km2
area. During the study, there was a prolonged El Nino-Southern Oscillation
period. Bees were collected by entomological nets, malaise traps, eugenol scent
trapping, and nest traps. Shannon index was calculated to estimate diversity and
Simpson index to determine dominance of a species. The effect of environmental
conditions (wet and dry season) in richness and abundance was analyzed by paired
T tests. A total of 3004 bee specimens were collected, belonging to 80 species
from Apidae, Megachilidae, Halictidae, and Colletidae. Apidae was the most
diverse. Shannon index value was 2.973 (discarding Apis mellifera Linnaeus 1758
data); thus, DsT can be considered as a zone of high wild bee diversity. Dry and
rainy season showed differences in diversity (p < 0.05). Rainy season showed
larger blooming periods and higher bee diversity than dry season. In both
seasons, social species were dominant (e.g., A. mellifera or Trigona fulviventris
Guerin 1844). Although DsT is a highly disturbed ecosystem, this study found it
has the second highest number of genera and the fourth highest number of species
reported in Colombia.
PMID- 29330669
TI - Hip and Groin Injuries in Baseball Players.
AB - PURPOSE OF REVIEW: To discuss the clinical significance of the most common hip
and groin injuries in baseball players, as well as an algorithmic approach to
diagnosis and treatment of these injuries. RECENT FINDINGS: (a) Limitations in
throwing velocity, pitch control, and bat swing speed may be secondary to
decreased mobility and strength within the proximal kinetic chain, which must
harness power from the lower extremities and core. (b) Approximately 5.5% of all
baseball injuries per year involve the hip/groin and may lead to a significant
amount of time spent on the disabled list. Injuries involving the hip and groin
are relatively common in baseball players. Our knowledge of the mechanics of
overhead throwing continues to evolve, as does our understanding of the
contribution of power from the lower extremities and core. It is paramount that
the team physician be able to accurately diagnose and treat injuries involving
the hip/groin, as they may lead to significant disability and inability to return
to elite levels of play. This review focuses on hip- and groin-related injuries
in the baseball player, including femoroacetabular impingement, core muscle
injury, and osteitis pubis.
PMID- 29330668
TI - Impact of duplicate CT scan rate after implementation of transfer image
repository system at a level 1 trauma center.
AB - PURPOSE: The regionalization of trauma in the USA results in frequent transfers
of patients from a primary hospital ED to a higher level trauma facility. While
many hospitals have a Picture Archive Communication System (PACS) which captures
digital radiological images, these are often not available to the receiving
institution resulting in duplicate imaging. The state of Arkansas instituted a
trauma image repository (TIR) in July 2013. We examined whether implementation of
this repository would impact CT scan duplication in the trauma system. METHODS:
This was a retrospective analysis of trauma patients transferred from outlying
hospitals in Arkansas and Missouri to a single level 1 trauma hospital in
Missouri between July 2012 and June 2015. We compared the duplicate CT rate for
patients transferred from Arkansas and Missouri hospitals before and after the
repository was implemented for Arkansas. RESULTS: Prior to implementation (July
2012-June 2013) of Arkansas TIR, duplicate CT rates were similar for patients
transferred from Arkansas (11.5% +/- 2.8) or Missouri (16.3% +/- 7.5). Following
implementation (July 2013-June 2014), the duplicate CT rate for patients
transferred from Arkansas was significantly lower (Arkansas = 10.1% vs. Missouri
16.2%; CI 95%, p = 0.02), and significance continued (Arkansas = 9.0% vs.
Missouri = 17.8%; CI 95%, p = 0.02) during follow-up (July 2014-June 2015).
CONCLUSION: Fewer patients received duplicated scans within the Arkansas as
compared with the Missouri-based trauma referral systems regardless of Injury
Severity Scores (ISS). Our findings suggest that TIR adoption coupled with PACS
improved transferability of radiographic studies and could improve patient care
while reducing costs in trauma transfers.
PMID- 29330670
TI - Treatment of Partial Thickness Rotator Cuff Tears in Overhead Athletes.
AB - PURPOSE OF REVIEW: To review the etiology, classification, presentation,
evaluation, treatment strategy, and outcomes in overhead athletes with partial
thickness rotator cuff tears. RECENT FINDINGS: Despite advances in surgical
repair techniques, return to play following surgical repair of partial rotator
cuff tears remains modest at best. Overhead athletes may be particularly prone to
rotator cuff pathology due to the supraphysiological strains within the tendon
during the throwing motion, as well as mechanical stress with contact between the
undersurface of the rotator cuff and the glenoid. The true prevalence of partial
tears may be underestimated given the high incidence of asymptomatic tears. Both
dynamic ultrasound and enhanced contrast MRI have improved our understanding of
this pathology. For most overhead athletes, nonoperative management is the most
common course. Despite advances in imaging, diagnosis, and surgical techniques,
our ability to return these patients to their elite level is modest at best when
nonoperative management fails and surgical treatment is performed. If a surgical
route is needed, debridement alone is the most frequent procedure given concerns
of over constraint and poor return to play with surgical repair of the partial
thickness rotator cuff tear.
PMID- 29330672
TI - [Obituary for Prof. Dr. med. D. Sc. h.c. Robert F. Schmidt, Ph.D.]
PMID- 29330671
TI - Internalizing and Externalizing Behaviors Share a Common Predictor: the Effects
of Early Maladaptive Schemas Are Mediated by Coping Responses and Schema Modes.
AB - We investigated the relationships of adolescents' internalizing and externalizing
behaviors with their early maladaptive schemas (EMS), coping responses, and
schema modes. We focused on EMS related to experiences of disconnection and
rejection that comprise vulnerable emotions, such as shame, mistrust,
deprivation, abandonment, and isolation/alienation. This cross-sectional study
included a total of 699 adolescents (combined clinical and non-referred sample)
who were 11 to 18 years old (M = 14.6; SD = 1.6), and of which 45% was male. All
participants completed self-report questionnaires on EMS, coping responses,
schema modes, and behavior problems. We aimed to clarify the relationships
between these variables by testing mediation, moderation, and moderated mediation
models. In general, coping responses functioned as mediators rather than
moderators in the relationships between EMS and schema modes. Furthermore, EMS
regarding experiences of disconnection and rejection were related to both
internalizing and externalizing behavior problems, and coping responses and
schema modes mediated these effects. In conclusion, although adolescent
internalizing and externalizing behavior problems manifest quite differently,
they seem related to the same EMS.
PMID- 29330673
TI - Vacuum-assisted closure therapy of paradoxical reaction in tuberculous
lymphadenopathy caused by Mycobacterium africanum.
AB - A 26-year-old HIV-negative male from Ghana was treated for cervical,
intrathoracic and abdominal lymph node tuberculosis (TB) and tuberculous
hepatitis. Penetration of the thoracic trachea by a mediastinal lymph node had
caused bronchomucosal TB. Sputum culture grew M. africanum, sensitive to all
first-line antituberculous drugs. Four weeks after the beginning of directly
observed treatment with isoniazid, rifampin, pyrazinamide and ethambutol, the
right cervical lymph node increased in size, liquefied and caused a spontaneous
fistula. A biopsy of the necrotized lymph node revealed rare acid-fast bacilli
with a positive PCR for Mycobacterium tuberculosis complex. After debridement,
vacuum-assisted closure therapy was performed for 6 weeks. Five months after the
beginning of antituberculous therapy, a second paradoxical reaction occurred,
with painful swelling of two contralateral supraclavicular lymph nodes.
Extirpation of one node yielded a positive PCR for M. tuberculosis complex; the
culture was negative. Antituberculous treatment was continued, and additional
treatment with oral prednisolone 20 mg daily for 1 month tapering over 10 weeks
was introduced, resulting in a decrease in lymphadenopathy. Antituberculous
treatment was continued for a total of 9 months. The outcome was favorable, no
further lymphadenopathy occurred over the following 6 months.
PMID- 29330675
TI - Recognizing conserved non-canonical localization patterns of toll-like receptors
in tissues and across species.
AB - Toll-like receptors (TLR) 1, 2, 4, 5 and 6 were originally characterized as
exclusively expressed on the cell surface and TLR 3, 7, 8 and 9 were said to be
localized to the endosomes. However, continued research in this area shows that
TLR localization may be altered across cell-types, and in response to
stimulation, age or disease. Mucosal surfaces must remain tolerant to the
commensal flora and thus intracellular or basal lateral localization of TLRs at
mucosal surfaces may be necessary to prevent induction of an inflammatory
response to commensal flora while still allowing the possibility for the
receptors to prime an immune response when a pathogen has crossed the epithelial
barrier. Here, we highlight the research specifying 'non-canonical' localization
of TLRs in human and animal mucosal tissues and blood-derived cells, while
excluding cultured polarized immortalized cells. Reports that only indicate TLR
gene/protein expression and/or responsiveness to agonists have been excluded
unless the report also indicates surface/intracellular distribution in the cell.
Understanding the tissue- and species-specific localization of these specific
pattern recognition receptors will lead to a greater appreciation of the way in
which TLR ligands promote innate immunity and influence the adaptive immune
response. A more comprehensive understanding of this information will potentially
aid in the exploitation of the therapeutic or adjuvant potential of selectively
localized TLRs and in opening new perspectives in understanding the basis of
immunity.
PMID- 29330674
TI - Advances in serological, imaging techniques and molecular diagnosis of Toxoplasma
gondii infection.
AB - BACKGROUND: Toxoplasmosis is worldwide distributed zoonotic infection disease
with medical importance in immunocompromised patients, pregnant women and
congenitally infected newborns. Having basic information on the traditional and
new developed methods is essential for general physicians and infectious disease
specialists for choosing a suitable diagnostic approach for rapid and accurate
diagnosis of the disease and, consequently, timely and effective treatment.
METHODS: We conducted English literature searches in PubMed from 1989 to 2016
using relevant keywords and summarized the recent advances in diagnosis of
toxoplasmosis. RESULTS: Enzyme-linked immunosorbent assay (ELISA) was most used
method in past century. Recently advanced ELISA-based methods including
chemiluminescence assays (CLIA), enzyme-linked fluorescence assay (ELFA),
immunochromatographic test (ICT), serum IgG avidity test and immunosorbent
agglutination assays (ISAGA) have shown high sensitivity and specificity. Recent
studies using recombinant or chimeric antigens and multiepitope peptides method
demonstrated very promising results to development of new strategies capable of
discriminating recently acquired infections from chronic infection. Real-time PCR
and loop-mediated isothermal amplification (LAMP) are two recently developed PCR
based methods with high sensitivity and specificity and could be useful to early
diagnosis of infection. Computed tomography, magnetic resonance imaging, nuclear
imaging and ultrasonography could be useful, although their results might be not
specific alone. CONCLUSION: This review provides a summary of recent developed
methods and also attempts to improve their sensitivity for diagnosis of
toxoplasmosis. Serology, molecular and imaging technologies each has their own
advantages and limitations which can certainly achieve definitive diagnosis of
toxoplasmosis by combining these diagnostic techniques.
PMID- 29330677
TI - Evaluating Efficacy of Landsat-Derived Environmental Covariates for Predicting
Malaria Distribution in Rural Villages of Vhembe District, South Africa.
AB - Malaria in South Africa is still a problem despite existing efforts to eradicate
the disease. In the Vhembe District Municipality, malaria prevalence is still
high, with a mean incidence rate of 328.2 per 100,0000 persons/year. This study
aimed at evaluating environmental covariates, such as vegetation moisture and
vegetation greenness, associated with malaria vector distribution for better
predictability towards rapid and efficient disease management and control. The
2005 malaria incidence data combined with Landsat 5 ETM were used in this study.
A total of nine remotely sensed covariates were derived, while pseudo-absences in
the ratio of 1:2 (presence/absence) were generated at buffer distances of 0.5-20
km from known presence locations. A stepwise logistic regression model was
applied to analyse the spatial distribution of malaria in the area. A buffer
distance of 10 km yielded the highest classification accuracy of 82% at a
threshold of 0.9. This model was significant (rho < 0.05) and yielded a deviance
(D2) of 36%. The significantly positive relationship (rho < 0.05) between the
soil-adjusted vegetation index and malaria distribution at all buffer distances
suggests that malaria vector (Anopheles arabiensis) prefer productive and greener
vegetation. The significant negative relationship between water/moisture index
(a1 index) and malaria distribution in buffer distances of 0.5, 10, and 20 km
suggest that malaria distribution increases with a decrease in shortwave
reflectance signal. The study has shown that suitable habitats of malaria vectors
are generally found within a radius of 10 km in semi-arid environments, and this
insight can be useful to aid efforts aimed at putting in place evidence-based
preventative measures against malaria infections. Furthermore, this result is
important in understanding malaria dynamics under the current climate and
environmental changes. The study has also demonstrated the use of Landsat data
and the ability to extract environmental conditions which favour the distribution
of malaria vector (An. arabiensis) such as the canopy moisture content in
vegetation, which serves as a surrogate for rainfall.
PMID- 29330679
TI - ?
PMID- 29330676
TI - Quantitative Outcomes of a One Health approach to Study Global Health Challenges.
AB - Having gained momentum in the last decade, the One Health initiative promotes a
holistic approach to address complex global health issues. Before recommending
its adoption to stakeholders, however, it is paramount to first compile
quantitative evidence of the benefit of such an approach. The aim of this scoping
review was to identify and summarize primary research that describes monetary and
non-monetary outcomes following adoption of a One Health approach. An extensive
literature search yielded a total of 42,167 references, of which 85 were included
in the final analysis. The top two biotic health issues addressed in these
studies were rabies and malaria; the top abiotic health issue was air pollution.
Most studies described collaborations between human and animal (n = 42), or human
and environmental disciplines (n = 41); commonly reported interventions included
vector control and animal vaccination. Monetary outcomes were commonly expressed
as cost-benefit or cost-utility ratios; non-monetary outcomes were described
using disease frequency or disease burden measurements. The majority of the
studies reported positive or partially positive outcomes. This paper illustrates
the variety of health challenges that can be addressed using a One Health
approach, and provides tangible quantitative measures that can be used to
evaluate future implementations of the One Health approach.
PMID- 29330678
TI - [Quality indicators with reference values and threshold limits in general and
visceral surgery : For obesity and metabolic, pancreatic, colon carcinoma and
rectal carcinoma surgery].
PMID- 29330680
TI - The illusion of control: Sequential dependencies underlie contingent attentional
capture.
AB - The degree to which humans have top-down control over which information they
process remains a central debate within the attention literature. Most of the
evidence supporting the top-down control of visuospatial attention has come from
cueing paradigms in which target stimuli are preceded by cues that are similar or
dissimilar from the target. These studies find that the cues similar to targets
capture attention, but dissimilar cues do not, suggesting the top-down control of
attention. Here, we used a modified cueing paradigm to investigate an alternative
possibility that the cue type differences are due to sequential dependency
effects occurring between cue and target processing rather than the top-down
control of attention. When individuals searched for color targets, we replicated
contingent capture effects in RTs, which are susceptible to sequential
dependencies, but memory performance was always best at the cued locations,
regardless of the cue's identity. When individuals searched for onset targets, we
observed contingent capture in both tasks. These results demonstrate the utility
of the memory probe paradigm and suggest an asymmetry between how strongly onsets
and color defined cues capture attention.
PMID- 29330681
TI - Verification of nonwords: The baseword frequency effect in children's
pseudohomophone reading.
AB - In this study, we investigated the baseword frequency effect in children and its
implications for models of visual word recognition. The baseword frequency effect
reflects the finding that response latencies in the lexical decision task to
nonwords derived from high-frequency basewords (e.g., GREAN derived from GREEN)
are shorter than for those derived from low-frequency basewords (e.g., SLEAT
derived from SLEET). Importantly, the baseword frequency effect presents a
challenge to current activation-based models of visual word recognition. One
explanation for this effect is that the orthographic representations of high
frequency basewords are easier to access. This allows a quick progression to a
verification stage in which the exact spelling of a stimulus is checked, upon
which the lexicality decision is then based. The main goal of this study was to
investigate whether such a verification mechanism is specifically modulated by
the quality of the orthographic lexicon. We tested whether the baseword frequency
effect was evident in children's lexical decisions to pseudohomophones (PsH) and
whether verification accuracy varied as a function of children's orthographic
knowledge. The baseword frequency effect in response latency was observed in both
German-speaking adults and children. Children's spelling skills significantly
influenced the accuracy of the verification stage in their responses to PsH.
These findings imply that verification is an integral part of word reading and
thus should be included in computational models of visual word recognition.
PMID- 29330682
TI - Life-Threatening Reaction with Topical 5-Fluorouracil.
AB - A 67-year-old man developed a suspected adverse drug reaction during treatment
with topical 5-fluorouracil (5-FU) for multiple actinic keratosis of the face,
neck, and forearms. The man received topical 5-FU at a dosage of 0.5% for the
actinic keratoses. After 1 week, he developed extreme lethargy, fatigue, fever,
and mouth erosions. Several days later, and after discontinuation of 5-FU,
painful mucositis and systemic side effects occurred, meeting criteria for
hospitalization because of dehydration and a 6.8 kg weight loss.
Hematology/oncology was consulted, and a possible systemic 5-FU reaction, similar
to reactions to intravenous chemotherapy seen with a dihydropyrimidine
dehydrogenase deficiency was suggested. The patient was not taking any concurrent
medications, and he refused dihydropyrimidine dehydrogenase deficiency testing.
PMID- 29330683
TI - Cardiac function during weaning failure: the role of diastolic dysfunction.
AB - BACKGROUND: Cardiac dysfunction is a common cause of weaning failure. Weaning
shares some similarities with a cardiac stress test and may challenge active
phases of the cardiac cycle-like ventricular contractility and relaxation. This
study aimed at assessing systolic and diastolic function during the weaning
process and scrutinizing their dynamics during weaning trials. METHODS:
Echocardiography was performed during baseline ventilator settings to assess
cardiac function at the initiation of the weaning process and at the start and
the end of consecutive weaning trials (performed at day-1, day-2, and before
extubation if applicable) to explore the evolution of left ventricle
contractility and relaxation in a subset of patients. RESULTS: Among 67 patients
included, weaning was prolonged (>= 7 days) in 18 (27%) patients and short (< 7
days) in 49 (73%). Prevalence of systolic dysfunction and isolated diastolic
dysfunction before the initiation of weaning process were 37 and 17%,
respectively. Isolated diastolic dysfunction was more frequent in patients with
prolonged weaning as compared to their counterparts. Thirty-one patients were
explored by echocardiography during consecutive weaning trials. An increase in
filling pressures with an alteration of ventricular relaxation (as assessed by a
decrease in tissue Doppler early mitral diastolic wave velocity) was found during
failed weaning trials. CONCLUSIONS: Isolated diastolic dysfunction was associated
with a prolongation of weaning. Increased filling pressures with left ventricle
relaxation impairment may be a key mechanism of weaning trial failure.
PMID- 29330684
TI - Investigation of Mature BDNF and proBDNF Signaling in a Rat Photothrombotic
Ischemic Model.
AB - Treatment with mature brain-derived neurotrophic factor (mBDNF) promotes
functional recovery after ischemia in animal trials but the possible role of its
precursor protein proBDNF and its receptors or the factors responsible for the
conversion of proBDNF to mBDNF in ischemic stroke are not known. The main aim of
this study was to characterize the time-dependent expression of genes and/or
proteins related to BDNF processing and signaling after ischemia as well as the
sensorimotor behavioral dysfunction in a photothrombotic ischemic model in rats.
Characterization of different genes and proteins related to BDNF processing and
signaling was performed using qPCR, immunoblotting and enzyme-linked
immunosorbent assays. We showed in this study that some sensory and motor
functional deficiencies appeared in the ischemic group at day 1 and persisted
until day 14. Most changes in gene expression of BDNF and its processing enzymes
occurred within the first 24 h in the ipsilateral cortex, but not in the
contralateral cortex. At the protein level, proBDNF expression was increased at 6
h, mBDNF expression was increased between 15 h and 1 day while p75 receptor
protein expression was increased between 6 h and 3 days in the ipsilateral
cortex, but not in the contralateral cortex. Therefore, cerebral ischemia in rats
led to the up-regulation of genes and/or proteins of BDNF, proBDNF and their
processing enzymes and receptors in a time-dependent manner. We propose that the
balance between BDNF and proBDNF and their associated proteins may play an
important role in the pathogenesis and recovery from ischemia.
PMID- 29330685
TI - Do we understand the rationale behind driving restrictions in patients with an
implantable cardioverter defibrillator?
PMID- 29330686
TI - Attentional influences on memory formation: A tale of a not-so-simple story.
AB - Is there a learning mechanism triggered by mere expectation violation? Is there
some form of memory enhancement inherent to an event mismatching our predictions?
Across seven experiments, we explore this issue by means of a validity paradigm.
Although our manipulation clearly succeeded in generating an expectation and
breaking it, the memory consequences of that expectation mismatch are not so
obvious. We report here evidence of a null effect of expectation on memory
formation. Our results (1) show that enhanced memory for unexpected events is not
easily achieved and (2) call for a reevaluation of previous accounts of memory
enhancements based on prediction error or difficulty of processing. Limitations
of this study and possible implications for the field are discussed in detail.
PMID- 29330687
TI - Evaluation of the Mitochondria-Related Redox and Bioenergetics Effects of
Gastrodin in SH-SY5Y Cells Exposed to Hydrogen Peroxide.
AB - Mitochondrion is the main site of ATP production in animal cells and also
orchestrates signaling pathways associated with cell survival and death.
Mitochondrial dysfunction has been linked to bioenergetics and redox impairment
in human diseases, such as neurodegeneration and cardiovascular disease.
Protective agents able to attenuate mitochondrial impairment are of
pharmacological interest. Gastrodin (GAS; 4-hydroxybenzyl alcohol 4-O-beta-D
glucoside) is a phenolic glucoside obtained from the Chinese herbal medicine
Gastrodia elata Blume and exhibits antioxidant, anti-inflammatory, and
antiapoptotic effects in several cell types. GAS is able to cross the blood-brain
barrier, reducing the impact of different stressors on the cognition of
experimental animals. In the present work, we investigated whether GAS would
protect mitochondria of human SH-SY5Y neuroblastoma cells against an exposure to
a pro-oxidant agent. The cells were treated with GAS at 25 MUM for 30 min before
the administration of hydrogen peroxide (H2O2) at 300 MUM for an additional 3 or
24 h, depending on the assay. We evaluated both mitochondrial redox state and
function parameters and analyzed the mechanism by which GAS protected
mitochondria in this experimental model. Silencing of the nuclear factor
erythroid 2-related factor 2 (Nrf2) transcription factor suppressed the GAS
induced mitochondrial protection seen here. Moreover, Nrf2 knockdown abrogated
the effects of GAS on cell viability, indicating a potential role for Nrf2 in
both mitochondrial and cellular protection promoted by GAS. Further research
would be necessary to investigate whether GAS would be able to induce similar
effects in in vivo experimental models.
PMID- 29330688
TI - Hepatocyte nuclear factors as possible C-reactive protein transcriptional inducer
in the liver and white adipose tissue of rats with experimental chronic renal
failure.
AB - Inflammation related to chronic kidney disease (CKD) is an important clinical
problem. We recently determined that hepatocyte nuclear factor 1alpha (HNF1alpha)
was upregulated in the livers of chronic renal failure (CRF) rats-experimental
model of CKD. Considering that the promoter region of gene encoding C-reactive
protein (CRP) contains binding sites for HNF1alpha and that the loss-of-function
mutation in the Hnfs1alpha leads to significant reduction in circulating CRP
levels, we hypothesized that HNF1alpha can activate the Crp in CRF rats. Here, we
found coordinated upregulation of genes encoding CRP, interleukin-6 (IL-6),
HNF1alpha, and HNF4alpha in the livers and white adipose tissue (WAT) of CRF
rats, as compared to the pair-fed and control animals. This was accompanied by
elevated serum levels of CRP and IL-6. CRP and HNFs' mRNA levels correlated
positively with CRP and HNFs' protein levels in the liver and WAT. Similar
upregulation of the Crp, Il-6, and Hnfs in the liver and WAT and increased serum
CRP and IL-6 concentrations were found in lipopolysaccharide (LPS)-induced
systemic inflammation in rats. Moreover, silencing HNF1alpha in HepG2 cells by
small interfering RNA led to decrease in CRP mRNA levels. Our results suggests
that (a) HNFs act in concert with IL-6 in the upregulation of CRP production by
the liver and WAT, leading to an increase in circulating CRP concentration in CRF
rats and (b) CRF-related inflammation plays an important role in the upregulation
of genes that encode HNFs and CRP in the liver and WAT of CRF rats.
PMID- 29330689
TI - The efficiency of acoustic radiation force impulse (ARFI) elastography in the
diagnosis and staging of carpal tunnel syndrome.
AB - OBJECTIVES: The aim of the present study was to quantify the stiffness of the
median nerve (MN) at the carpal tunnel inlet by acoustic radiation force impulse
(ARFI) elastography and to evaluate whether ARFI can be used in diagnosis and
staging of carpal tunnel syndrome (CTS). METHODS: Sonographic examinations of 96
wrists in 50 patients were included in the study. The cross-sectional area and
stiffness of the MN were quantitatively measured by B-mode ultrasonography (USG)
and ARFI. The findings of CTS were assigned to four groups: (I) normal (n = 21),
(II) mild (n = 39), (III) moderate (n = 38), and (IV) severe (n = 19). The
differences between CTS patients and controls and the differences in
electrodiagnostic tests among subgroups were statistically compared. ROC analysis
was performed to determine the cut-off values between subgroups. RESULTS:
Bilateral CTS was present in 46 patients (92 wrists) and unilateral CTS in four
patients. Of the 96 nerves in the 50 symptomatic "idiopathic CTS" patients (48
women, 2 men; mean age 45.9 years, range 23-73 years), 39 (40.4%) were mild, 38
(39.8%) were moderate, and 19 (19.8%) were severely affected. When compared to
controls, MN stiffness was significantly higher in the CTS group (P < 0.001);
furthermore, it was higher in the severe or extreme severity group than the mild
or moderate severity group (P < 0.001). A 3.250 m/s cut-off value on ARFI
revealed sensitivity, specificity, positive predictive value, negative predictive
value, and accuracy of 81, 82, 95.1, 50, and 82%, respectively. CONCLUSION: The
MN stiffness measured by ARFI elastography is significantly higher in patients
with CTS then in controls. ARFI elastography appears to be a highly efficient
imaging modality for the diagnosis and staging of these patients.
PMID- 29330690
TI - Extracorporeal membrane oxygenation for severe Middle East respiratory syndrome
coronavirus.
AB - BACKGROUND: Middle East respiratory syndrome (MERS) is caused by a coronavirus
(MERS-CoV) and is characterized by hypoxemic respiratory failure. The objective
of this study is to compare the outcomes of MERS-CoV patients before and after
the availability of extracorporeal membrane oxygenation (ECMO) as a rescue
therapy in severely hypoxemic patients who failed conventional strategies.
METHODS: We collected data retrospectively on MERS-CoV patients with refractory
respiratory failure from April 2014 to December 2015 in 5 intensive care units
(ICUs) in Saudi Arabia. Patients were classified into two groups: ECMO versus
conventional therapy. Our primary outcome was in-hospital mortality; secondary
outcomes included ICU and hospital length of stay. RESULTS: Thirty-five patients
were included; 17 received ECMO and 18 received conventional therapy. Both groups
had similar baseline characteristics. The ECMO group had lower in-hospital
mortality (65 vs. 100%, P = 0.02), longer ICU stay (median 25 vs. 8 days,
respectively, P < 0.01), and similar hospital stay (median 41 vs. 31 days, P =
0.421). In addition, patients in the ECMO group had better PaO2/FiO2 at days 7
and 14 of admission to the ICU (124 vs. 63, and 138 vs. 36, P < 0.05), and less
use of norepinephrine at days 1 and 14 (29 vs. 80%; and 36 vs. 93%, P < 0.05).
CONCLUSIONS: ECMO use, as a rescue therapy, was associated with lower mortality
in MERS patients with refractory hypoxemia. The results of this, largest to date,
support the use of ECMO as a rescue therapy in patients with severe MERS-CoV.
PMID- 29330691
TI - Bis-guanylhydrazones as efficient anti-Candida compounds through DNA interaction.
AB - Candida spp. are leading causes of opportunistic mycoses, including life
threatening hospital-borne infections, and novel antifungals, preferably aiming
targets that have not been used before, are constantly needed. Hydrazone- and
guanidine-containing molecules have shown a wide range of biological activities,
including recently described excellent antifungal properties. In this study, four
bis-guanylhydrazone derivatives (BG1-4) were generated following a previously
developed synthetic route. Anti-Candida (two C. albicans, C. glabrata, and C.
parapsilosis) minimal inhibitory concentrations (MICs) of bis-guanylhydrazones
were between 2 and 15.6 MUg/mL. They were also effective against preformed 48-h
old C. albicans biofilms. In vitro DNA interaction, circular dichroism, and
molecular docking analysis showed the great ability of these compounds to bind
fungal DNA. Competition with DNA-binding stain, exposure of phosphatidylserine at
the outer layer of the cytoplasmic membrane, and activation of metacaspases were
shown for BG3. This pro-apoptotic effect of BG3 was only partially due to the
accumulation of reactive oxygen species in C. albicans, as only twofold MIC and
higher concentrations of BG3 caused depolarization of mitochondrial membrane
which was accompanied by the decrease of the activity of fungal mitochondrial
dehydrogenases, while the activity of oxidative stress response enzymes
glutathione reductase and catalase was not significantly affected. BG3 showed
synergistic activity with amphotericin B with a fractional inhibitory
concentration index of 0.5. It also exerted low cytotoxicity and the ability to
inhibit epithelial cell (TR146) invasion and damage by virulent C. albicans
SC5314. With further developments, BG3 may further progress in the antifungal
pipeline as a DNA-targeting agent.
PMID- 29330692
TI - A new method for the in vitro determination of the bile tolerance of potentially
probiotic lactobacilli.
AB - A new in vitro method was developed to determine the bile tolerance of
potentially probiotic lactobacilli. The overnight culture of various lactobacilli
strains was inoculated into sterile, half-strength MRS broth supplemented with
and without 0.3% (wt/vol) oxgall, buffered with 0.1 M sodium phosphate buffer at
a final pH of 7.3, and incubated at 37 degrees C for 12 h under anaerobic
conditions. The bile tolerance ability of the lactobacilli strains was expressed
as the percentage of the propagation generations of the bacterial cells in the
presence of oxgall to those in the absence of oxgall. The bile tolerance ability
of 11 strains of 8 Lactobacillus species, including 3 bile salt hydrolase (BSH)
negative strains and 8 BSH-positive strains, was analyzed using the newly
developed method and two traditional methods. The results showed that bile
tolerance ability of the strains was considerably different depending on the
analysis method used. The newly developed method mimics the physiological
environment of the human small intestine, and avoids changes in pH and bile salt
composition during the incubation period, which are drawbacks of the traditional
bile tolerance test methods. Therefore, the analysis method developed in this
study is more suitable to screen or compare the bile tolerance ability of
lactobacilli strains.
PMID- 29330693
TI - The enhanced biomass and lipid accumulation in Coccomyxa subellipsoidea with an
integrated treatment strategy initiated by brewery effluent and phytohormones.
AB - Brewery effluent (BE) as an appreciable and sustainable resource presented new
possibilities in low-cost algal biomass production, whereas the relatively low
essential macronutrients hindered extensive applications as growth medium for
microalgae cultivation. The objective of this study was to investigate the
feasibility of an integrated treatment strategy initiated by BE coupling
phytohormones in augmenting biomass and lipid accumulation in Coccomyxa
subellipsoidea. Results revealed that BE coupling synthetic 1-naphthaleneacetic
acid (NAA) accomplished the favorable lipid productivity of 481.76 mg/L/days,
representing 6.80- to 9.71-fold more than that of single BE as well as standard
Basal media. BE coupling NAA feeding also heightened the proportions of C16-C18
fatty acids (over 96%) and mono-unsaturated C18:1 (approximate 45%) which were
prone to high-quality biofuels-making. Such profound lipids accumulation might be
attributable to that BE coupling NAA treatment drove most of metabolic flux (i.e.
acetyl-CoA) derived from TCA cycle and glycolysis flowing into lipid accumulation
pathway. Concurrently, the complete removal of total nitrogen and total
phosphorus by C. subellipsoidea with assistance of NAA were easily complied with
the permissible dischargeable limits for BE. These present results strongly
demonstrated that BE coupling NAA was a potential feeding strategy in boosting
algal lipid productivity and further provided great possibilities in linking
affordable algal biomass production with high-efficient biological contaminants
removal.
PMID- 29330694
TI - Volatile compounds from beneficial or pathogenic bacteria differentially regulate
root exudation, transcription of iron transporters, and defense signaling
pathways in Sorghum bicolor.
AB - KEY MESSAGE: Our results show that Sorghum bicolor is able to recognize bacteria
through its volatile compounds and differentially respond to beneficial or
pathogens via eliciting nutritional or defense adaptive traits. Plants establish
beneficial, harmful, or neutral relationships with bacteria. Plant growth
promoting rhizobacteria (PGPR) emit volatile compounds (VCs), which may act as
molecular cues influencing plant development, nutrition, and/or defense. In this
study, we compared the effects of VCs produced by bacteria with different
lifestyles, including Arthrobacter agilis UMCV2, Bacillus methylotrophicus M4-96,
Sinorhizobium meliloti 1021, the plant pathogen Pseudomonas aeruginosa PAO1, and
the commensal rhizobacterium Bacillus sp. L2-64, on S. bicolor. We show that VCs
from all tested bacteria, except Bacillus sp. L2-64, increased biomass and
chlorophyll content, and improved root architecture, but notheworthy A. agilis
induced the release of attractant molecules, whereas P. aeruginosa activated the
exudation of growth inhibitory compounds by roots. An analysis of the expression
of iron-transporters SbIRT1, SbIRT2, SbYS1, and SbYS2 and genes related to plant
defense pathways COI1 and PR-1 indicated that beneficial, pathogenic, and
commensal bacteria could up-regulate iron transporters, whereas only beneficial
and pathogenic species could induce a defense response. These results show how S.
bicolor could recognize bacteria through their volatiles profiles and highlight
that PGPR or pathogens can elicit nutritional or defensive traits in plants.
PMID- 29330695
TI - Glucosuria and all-cause mortality among general screening participants.
AB - BACKGROUND: Dipstick urine tests are used for general health screening in Japan,
but how the test results (e.g., glucosuria) relate to mortality is unknown.
METHODS: Subjects participated in a nationwide screening in 2008 in six districts
in Japan. We identified those who might have died using the national database of
death certificates from 2008 to 2012 (total registered ~ 6 million) and verified
candidates with the regional National Health Insurance Agency and public health
nurses. Diabetes mellitus (DM) was defined as HbA1c >= 6.5%, fasting blood
glucose >= 126 mg/dl, or medicated for DM. Hazard ratio (HR) and 95% confidence
interval (CI) were calculated by Cox proportional hazard analysis. Glucosuria was
defined as dipstick >= 1 +. RESULTS: Among 209,060 subjects, we identified 2714
fatalities (median follow-up 3.57 years). Crude mortality rates were 1.2% for
those without glucosuria and 3.4% for those with glucosuria. After adjusting for
sex, age, body mass index, comorbidity (DM, hypertension, and dyslipidemia),
history (stroke, heart disease, and kidney disease), and lifestyle (smoking,
drinking, walking, and exercise), the HR (95% CI) for dipstick glucosuria was
1.475 (1.166-1.849, P < 0.001). DM subjects with glucosuria (N = 4655) had a
higher HR [1.302 (1.044-1.613, P = 0.020)] than DM subjects without glucosuria (N
= 20,245), and non-DM subjects with glucosuria (N = 470) had a higher HR [2.511
(1.539-3.833, P < 0.001)] than non-DM subjects without glucosuria (N = 183,690).
CONCLUSION: Dipstick glucosuria significantly affected mortality in Japanese
community-based screening participants.
PMID- 29330696
TI - Migrant Live-in Caregivers Mental Health in Canada.
AB - Empirical evidence suggests rapid health decline among temporary migrant workers
but there is limited knowledge about their mental health. This study explored
live-in care givers' (LCs) mental health and its determinants. Using a mixed
methods design, a purposeful sample of 30 LCs was recruited. Data were collected
through a selfcompleted questionnaire. A third of participants reported their
mental health as poor or fair. Almost half experienced major depression. The poor
mental health was associated with the average working hours and living
accommodation. The average resiliency scores was moderately high and appeared to
function as a protective factor against mental illness. Our findings suggest LCs
are at risk of compromised mental health associated to their substandard working
and living conditions. These conditions originates from violation of employment
contracts, unfair employment practices, and the lack of enforcement of LCs' legal
and human rights.
PMID- 29330697
TI - Implementation of Dialectical Behavior Therapy in Residential Treatment Programs:
A Process Evaluation Model for a Community-Based Agency.
AB - Dialectical behavior therapy (DBT) can be challenging to implement in community
based settings. Little guidance is available on models to evaluate the
effectiveness or sustainability of training and implementation efforts.
Residential programs have much to gain from introduction of evidence-based
practices, but present their own challenges in implementation. This paper
presents a low-cost process evaluation model to assess DBT training piloted in
residential programs. The model targets staff and organizational factors
associated with successful implementation of evidence-based practices and matches
data collection to the four stages of the DBT training model. The strengths and
limitations of the evaluation model are discussed.
PMID- 29330699
TI - Accounting of GHG emissions and removals from forest management: a long road from
Kyoto to Paris.
AB - BACKGROUND: Forests have always played an important role in agreeing on
accounting rules during the past two decades of international climate policy
development. Starting from activity-based gross-net accounting of selected
forestry activities to mandatory accounting against a baseline-rules have changed
quite rapidly and with significant consequences for accounted credits and debits.
Such changes have direct consequences on incentives for climate-investments in
forestry. There have also been strong arguments not to include forests into the
accounting system by considering large uncertainties, procedural challenges and a
fear of unearned credits corrupting the overall accounting system, among others.
This paper reflects the development of respective accounting approaches and
reviews the progress made on core challenges and resulting incentives. MAIN TEXT:
The historic development of forest management accounting rules is analysed in the
light of the Paris Agreement. Pros and cons of different approaches are discussed
with specific focus on the challenge to maintain integrity of the accounting
approach and on resulting incentives for additional human induced investments to
increase growth for future substitution and increased C storage by forest
management. The review is solely based on scientific publications and official
IPCC and UNFCC documents. Some rather political statements of non-scientific
stakeholders are considered to reflect criticism. Such sources are indicated
accordingly. Remaining and emerging requirements for an accounting system for
post 2030 are highlighted. CONCLUSIONS: The Paris Agreement is interpreted as a
"game changer" for the role of forests in climate change mitigation. Many
countries rely on forests in their NDCs to achieve their self-set targets. In
fact, the agreement "to achieve a balance between anthropogenic emissions by
sources and removals by sinks of greenhouse gases in the second half of this
century" puts pressure on the entire land sector to contribute to overall GHG
emission reductions. This also concerns forests as a resource for the bio-based
economy and wood products, and for increasing carbon reservoirs. By discussing
the existing elements of forest accounting rules and conditions for establishing
an accounting system post 2030, it is concluded that core requirements like
factoring out direct human-induced from indirect human-induced and natural
impacts on managed lands, a facilitation of incentives for management changes and
providing safeguards for the integrity of the accounting system are not
sufficiently secured by currently discussed accounting rules. A responsibility to
fulfil these basic requirements is transferred to Nationally Determined
Contributions. Increased incentives for additional human induced investments are
not stipulated by the accounting approach but rather by the political decision to
make use of the substitution effect and potential net removals from LULUCF to
contribute to self-set targets.
PMID- 29330698
TI - Circulating Hormones and Mammographic Density in Premenopausal Women.
AB - Prior research suggests that several endogenous hormones in premenopausal women
are associated with breast cancer risk; however, few studies have evaluated
associations of endogenous hormones with mammographic density (MD) in
premenopausal women. We conducted a cross-sectional study of plasma hormone
levels in relation to MD among 634 cancer-free premenopausal women in the Nurses'
Health Study II. We measured percent MD from screening mammograms using a
computer-assisted method. We assayed estradiol, estrone, and estrone sulfate in
blood samples timed in early follicular and mid-luteal phases of the menstrual
cycle as well as testosterone, androstenedione, progesterone,
dehydroepiandrosterone (DHEA), DHEA sulfate, sex hormone-binding globulin (SHBG),
and anti-Mullerian hormone in luteal or untimed samples. We used multivariable
linear regression to quantify the association of %MD with quartiles of each
hormone, adjusting for age, body mass index, and breast cancer risk factors.
Women in the highest quartile of follicular estradiol levels had significantly
greater %MD compared to those in the lowest quartile [difference, 6.7 percentage
points; 95% confidence interval (CI) 2.2, 11.3; p-trend < 0.001]. Similar
associations were observed for follicular free estradiol but not luteal-phase
estradiol. Also, women in the top (vs. bottom) quartile of free testosterone had
significantly lower %MD (difference, - 4.7; 95% CI - 8.7, - 0.8; p-trend = 0.04).
Higher SHBG was significantly associated with higher percent MD (difference, 4.8;
95% CI 1.1, 8.6; p-trend = 0.002). Percent MD was not strongly associated with
other measured hormones. Results were similar in analyses that excluded women
with anovulatory cycles. Our findings suggest that follicular estradiol and SHBG
may play an important role in premenopausal percent MD.
PMID- 29330700
TI - Relation between internalizing behaviors, externalizing behaviors, and peer
victimization among children with and without ADHD.
AB - The current study explored the concurrent and longitudinal association between
internalizing behaviors, externalizing behaviors, and peer victimization among
children with and without ADHD. Eighty children (42 ADHD, 38 non-ADHD) ages 8-12
participated in the present study conducted over a 6-month period. During the
baseline session, parents completed a structured diagnostic interview and the
Vanderbilt ADHD Parent Rating Scale to determine whether their child met criteria
for ADHD, and the Child Behavior Checklist (CBCL) to assess their child's
internalizing and externalizing behaviors; children completed the Perception of
Peer Support Scale (PPSS) to assess experiences of peer victimization. At the 6
month follow-up session, parents completed the CBCL and children completed the
PPSS. Concurrently, internalizing behaviors were associated with peer
victimization among children with and without ADHD; ADHD moderated this relation,
such that internalizing behaviors were more strongly related to peer
victimization among children with ADHD. Longitudinally, internalizing behaviors
at baseline predicted peer victimization at 6-month follow-up; however, further
analyses demonstrated there was a covarying change in internalizing behaviors and
peer victimization. These findings suggest internalizing behaviors are related to
peer victimization concurrently, and over time, and are associated with increased
risk for peer victimization in the presence of ADHD. Additionally, internalizing
behaviors and peer victimization appear to share a dynamic relationship; that is,
decreases in internalizing behaviors predict similar decreases in peer
victimization. No significant relations were observed between externalizing
behaviors and peer victimization. Implications and limitations are discussed.
PMID- 29330701
TI - ?
PMID- 29330702
TI - pTAC10, an S1-domain-containing component of the transcriptionally active
chromosome complex, is essential for plastid gene expression in Arabidopsis
thaliana and is phosphorylated by chloroplast-targeted casein kinase II.
AB - In higher plant chloroplasts, the plastid-encoded RNA polymerase (PEP) consists
of four catalytic subunits and numerous nuclear-encoded accessory proteins,
including pTAC10, an S1-domain-containing protein. In this study, pTAC10 knockout
lines were characterized. Two ptac10 mutants had an albino phenotype and severely
impaired chloroplast development. The pTAC10 genomic sequence fused to a four
tandem MYC tag driven by its own promoter functionally complemented the ptac10-1
mutant phenotype. pTAC10 was present in both the chloroplast stroma and
thylakoids. Two-dimensional blue native polyacrylamide gel electrophoresis (BN
PAGE), and immunoblotting assays showed that pTAC10:MYC co-migrates with one of
the PEP core subunits, RpoB. A comprehensive investigation of the plastid gene
expression profiles by quantitative RT-PCR revealed that, compared with wild-type
plants, the abundance of PEP-dependent plastid transcripts is severely decreased
in the ptac10-1 mutant, while the amount of plastid transcripts exclusively
transcribed by NEP either barely changes or even increases. RNA blot analysis
confirmed that PEP-dependent chloroplast transcripts, including psaB, psbA and
rbcL, substantially decrease in the ptac10-1 mutant. Immunoblotting showed
reduced accumulation of most chloroplast proteins in the ptac10 mutants. These
data indicate the essential role of pTAC10 in plastid gene expression and plastid
development. pTAC10 interacts with chloroplast-targeted casein kinase 2 (cpCK2)
in vitro and in vivo and can be phosphorylated by Arabidopsis cpCK2 in vitro at
sites Ser95, Ser396 and Ser434. RNA-EMSA assays showed that pTAC10 is able to
bind to the psbA, atpE and accD transcripts, suggesting a non-specific RNA
binding activity of pTAC10. The RNA affinity of pTAC10 was enhanced by
phosphorylation and decreased by the amino acid substitution Ser434-Ala of
pTAC10. These data show that pTAC10 is essential for plastid gene expression in
Arabidopsis and that it can be phosphorylated by cpCK2.
PMID- 29330703
TI - Association Between Atrial, Ventricular and Vascular Morphofunctional Alterations
in Rheumatoid Arthritis.
AB - INTRODUCTION: Rheumatoid arthritis (RA) represents a risk of non-fatal and
cardiovascular events. The aim of the present study was to evaluate
simultaneously left and right atrial and ventricular function, as well as
arterial stiffness, in RA patients. METHODS: This cross-sectional study included
55 consecutive RA patients and 55 healthy age and gender-matched controls. Blood
pressure and arterial stiffness were assessed in all participants, who also
underwent a complete echocardiographic examination. RESULTS: RA patients were
treated with steroid therapy (52.7%), methotrexate (66.6%) and biological therapy
(54.5%). Disease activity score revealed low average RA activity. Augmentation
index was significantly higher in RA patients (32.2 +/- 8.6 vs. 28.4 +/- 8.9%, P
= 0.02). Left atrial volume was also higher among RA patients (23.1 +/- 8.2 vs.
20.1 +/- 7.1 ml/m2, P = 0.04), whereas mitral and tricuspid E/A ratios were
significantly lower in RA individuals (0.90 +/- 0.24 vs. 1.03 +/- 0.35, P = 0.02;
1.07 +/- 0.31 vs. 1.27 +/- 0.35, P = 0.003, respectively). Tissue Doppler
systolic and diastolic velocities were similar between the observed groups.
Arterial stiffness index showed significant correlation with disease duration (r
= 0.29; P = 0.03). Tissue Doppler-derived transmitral late diastolic velocity
(A') showed significant correlation with index of disease activity in the RA
patients. CONCLUSIONS: Our results showed that left and right ventricular
diastolic function and arterial stiffness were significantly deteriorated in the
RA patients comparing with controls. The assessment of left and right ventricular
diastolic function, as well as vascular function, should be an essential part of
clinical evaluation in the RA patients.
PMID- 29330704
TI - The Effects of Coenzyme Q10 Supplementation on Blood Pressures Among Patients
with Metabolic Diseases: A Systematic Review and Meta-analysis of Randomized
Controlled Trials.
AB - INTRODUCTION: Although several trials have assessed the effect of coenzyme Q10
(CoQ10) supplementation on blood pressures among patients with metabolic
diseases, findings are controversial. AIM: This review of randomized controlled
trials (RCTs) was performed to summarize the evidence on the effects of CoQ10
supplementation on blood pressures among patients with metabolic diseases.
METHODS: Randomized-controlled trials (RCTs) published in PubMed, EMBASE, Web of
Science and Cochrane Library databases up to 10 August 2017 were searched. Two
review authors independently assessed study eligibility, extracted data, and
evaluated risk of bias of included studies. Heterogeneity was measured with a Q
test and with I2 statistics. Data were pooled by using the fix or random-effect
model based on the heterogeneity test results and expressed as standardized mean
difference (SMD) with 95% confidence interval (CI). RESULTS: A total of seventeen
randomized controlled trials (684 participants) were included. Results showed
that CoQ10 supplementation significantly decreased systolic blood pressure (SBP)
(SMD - 0.30; 95% CI - 0.52, - 0.08). However, CoQ10 supplementation decreased
diastolic blood pressure (DBP), but this was not statistically significant (SMD -
0.08; 95% CI - 0.46, 0.29). CONCLUSIONS: CoQ10 supplementation may result in
reduction in SBP levels, but did not affect DBP levels among patients with
metabolic diseases. Additional prospective studies regarding the effect of CoQ10
supplementation on blood pressure in patients with metabolic diseases are
necessary.
PMID- 29330705
TI - Association between skeletal morphology and agenesis of all four third molars in
Japanese orthodontic patients.
AB - The purpose of this study was to clarify differences in skeletal morphologies
between male and female orthodontic patients with and without agenesis of all
four third molars. A total of 64 patients (32 males and 32 females) with agenesis
of all four third molars without agenesis of other teeth were selected as the
third molars agenesis group (group 1). In addition, 64 patients (32 males and 32
females) with all these teeth were selected as controls (group 2). Lateral
cephalograms taken between the ages of 14 and 30 years were used to compare
skeletal morphology between groups 1 and 2 and between sexes. Maxillary length (P
< 0.001), lower facial height (P < 0.05), gonial angle (P < 0.001) and mandibular
plane angle (P < 0.001) were significantly smaller in group 1 than in group 2.
Irrespective of the presence or absence of all four third molars, males had
significantly smaller lower facial height (P < 0.01) and mandibular plane angle
(P < 0.001) and significantly greater total mandibular length (P < 0.001),
mandibular body length (P < 0.001) and mandibular ramus height (P < 0.001) than
females. Japanese orthodontic patients with agenesis of all four third molars had
significantly small maxillary length, lower facial height, gonial angle and
mandibular plane angle.
PMID- 29330706
TI - Color stability of different composite resins after polishing.
AB - The goals of the present study were to evaluate, in vitro, the staining of
different composite resins submitted to different common beverages, and to
compare the staining effect of each of these solutions. A total of 288 specimens
were randomly divided into six groups and immersed for 4 weeks in five staining
solutions represented by red wine, orange juice, coke, tea and coffee or in
artificial saliva as a control group. When analyzed over a black background, mean
DeltaE00 values varied from 0.8 for Venus Diamond, Saremco Microhybrid and ELS in
saliva and Estelite Posterior in coke to 37.6 for Filtek Supreme in red wine.
When analyzed over a white background, mean DeltaE00 values varied from 0.5 for
Saremco Microhybrid in saliva to 51.1 for Filtek Supreme in red wine. All
materials showed significant changes in color after 4 weeks of immersion in
staining solutions. Significant differences were found between the tested
composite resins and also between the staining solutions.
PMID- 29330707
TI - Effects of periodontal treatment on carotid intima-media thickness in patients
with lifestyle-related diseases: Japanese prospective multicentre observational
study.
AB - Atherosclerosis, a chronic inflammatory disease in arterial blood vessels, is one
of the major causes of death in worldwide. Meanwhile, periodontal disease is a
chronic inflammatory disease caused by infection with periodontal pathogens such
as P. gingivalis (Porphyromonas gingivalis). Several studies have reported
association between periodontal infection and atherosclerosis, but direct
investigation about the effects of periodontal treatment on atherosclerosis has
not been reported. We have planned Japanese local clinics to determine the
relationship between periodontal disease and atherosclerosis under collaborative
with medical and dental care. A prospective, multicentre, observational study was
conducted including 38 medical patients with lifestyle-related diseases in the
stable period under consultation at participating medical clinics and 92
periodontal patients not undergoing medical treatment but who were consulting at
participating dental clinics. Systemic and periodontal examinations were
performed before and after periodontal treatment. At baseline, LDL-C (low-density
lipoprotein cholesterol) levels and percentage (%) of mobile teeth were
positively related to plasma IgG (immunoglobulin) antibody titer against P.
gingivalis with multivariate analysis. Corresponding to improvements in
periodontal clinical parameters after treatment, right and left max IMT (maximum
intima-media thickness) levels were decreased significantly after treatment (SPT
S: start of supportive periodontal therapy, SPT-1y: at 1 year under SPT, and SPT
3y: at 3 years under SPT). The present study has clarified our previous
univariate analysis results, wherein P. gingivalis infection was positively
associated with progression of atherosclerosis. Thus, routine screening using
plasma IgG antibody titer against P. gingivalis and periodontal treatment under
collaborative with medical and dental care may prevent cardiovascular accidents
caused by atherosclerosis.
PMID- 29330708
TI - Living with lymphoedema-the perspective of cancer patients: a qualitative study.
AB - PURPOSE: The aim of this study was to describe the lived experience of
lymphoedema and the barriers faced by cancer sufferers receiving physiotherapy
outpatient treatment. METHODS: A qualitative, phenomenological study was
performed. Purposeful sampling method was used. Data collection methods included
unstructured and semi-structured interviews and researcher field notes. A
thematic analysis was used. The study was conducted following the Consolidated
Criteria for Reporting Qualitative Research guidelines. RESULTS: Eleven patients
(62.18 +/- 10.14 years) (90.91% women) participated. One theme was identified
with different subgroups. The main theme 'Living a life with multiple barriers'
formed by the subthemes 'Discovering physical and psychological barriers',
'Searching information', 'Building relationships' and 'Controlling expenses'
displays the daily difficulties they must face in areas such as work. The
patients reported that lymphoedema is a constant emotional and physical
challenge. They need to adapt their lives to their new situation, learning how to
manage the lymphoedema. CONCLUSIONS: Patients considered lymphoedema as a
clinical situation with multiple barriers and they found that it does alter their
quality of life. These results can be applied in onco-haematology units to
develop specific protocols for customers.
PMID- 29330710
TI - Glycogen Production in Marine Cyanobacterial Strain Synechococcus sp. NKBG
15041c.
AB - An important feature offered by marine cyanobacterial strains over freshwater
strains is the capacity to grow in seawater, replacing the need for often-limited
freshwater. However, there are only limited numbers of marine cyanobacteria that
are available for genetic manipulation and bioprocess applications. The marine
unicellular cyanobacteria Synechococcus sp. strain NKBG 15041c (NKBG15041c) has
been extensively studied. Recombinant DNA technologies are available for this
strain, and its genomic information has been elucidated. However, an
investigation of carbohydrate production, such as glycogen production, would
provide information for inevitable biofuel-related compound production, but it
has not been conducted. In this study, glycogen production by marine
cyanobacterium NKBG15041c was investigated under different cultivation
conditions. NKBG15041c yielded up to 399 MUg/ml/OD730 when cells were cultivated
for 168 h in nitrogen-depleted medium (marine BG11DeltaN) after medium
replacement (336 h after inoculation). Cultivation under nitrogen-limited
conditions also yielded an accumulation of glycogen in NKBG15041c cells (1 mM
NaNO3, 301 MUg/ml/OD730; 3 mM NaNO3, 393 MUg/ml/OD730; and 5 mM NaNO3, 328
MUg/ml/OD730) under ambient conditions. Transcriptional analyses were carried out
for 13 putative genes responsible for glycogen synthesis and catabolism that were
predicted based on homology analyses with Synechocystis sp. PCC 6803 (PCC6803)
and Synechococcus sp. PCC7002 (PCC7002). The transcriptional analyses revealed
that glycogen production in NKBG15041c under nitrogen-depleted conditions can be
explained by the contribution of both increased carbon flux towards glycogen
synthesis, similar to PCC6803 and PCC7002, and increased transcriptional levels
of genes responsible for glycogen synthesis, which is different from the
conventionally reported phenomenon, resulting in a relatively high amount of
glycogen under ambient conditions compared to PCC6803 and PCC7002.
PMID- 29330712
TI - Correction to: Pre-existing Small Vessel Disease in Patients with Acute Stroke
from the Middle East, Southeast Asia, and Philippines.
AB - The author names "Dr. Pablo Garcia Bermejo" and "Dr. Muhammad Faisal Wadiwala"
needed to be added as the 6th and 7th authors, respectively. The authors regret
this error.
PMID- 29330709
TI - In vitro and in vivo activity of iclaprim, a diaminopyrimidine compound and
potential therapeutic alternative against Pneumocystis pneumonia.
AB - Pneumocystis pneumonia is a serious complication that may affect immunosuppressed
patients. The absence of reliable and safe therapeutic alternatives to
trimethoprim-sulfamethoxazole (TMP/SMX) justifies the search for more effective
and less toxic agents. In this study, the in vitro and in vivo anti-Pneumocystis
jirovecii activity of iclaprim, a diaminopyrimidine compound that exerts its
antimicrobial activity through the inhibition of dihydrofolate reductase (DHFR),
as does TMP, was evaluated alone or in combination with SMX. The antimicrobial
activity of iclaprim was tested in vitro using an efficient axenic culture
system, and in vivo using P. carinii endotracheally inoculated corticosteroid
treated rats. Animals were orally administered iclaprim (5, 25, 50 mg/kg/day),
iclaprim/SMX (5/25, 25/125, 50/250 mg/kg/day), TMP (50 mg/kg/day), or TMP/SMX
(50/250 mg/kg/day) once a day for ten consecutive days. The in vitro maximum
effect (Emax) and the drug concentrations needed to reach 50% of Emax (EC50) were
determined, and the slope of the dose-response curve was estimated by the Hill
equation (Emax sigmoid model). The iclaprim EC50 value was 20.3 MUg/mL. This
effect was enhanced when iclaprim was combined with SMX (EC50: 13.2/66 MUg/mL) (p
= 0.002). The TMP/SMX EC50 value was 51.4/257 MUg/mL. In vivo, the iclaprim/SMX
combination resulted in 98.1% of inhibition compared to TMP/SMX, which resulted
in 86.6% of inhibition (p = 0.048). Thus, overall, the iclaprim/SMX combination
was more effective than TMP/SMX both in vitro and in vivo, suggesting that it
could be an alternative therapy to the TMP/SMX combination for the treatment of
Pneumocystis pneumonia.
PMID- 29330713
TI - Low-field magnetic resonance imaging offers potential for measuring tibial
component migration.
AB - BACKGROUND: Roentgen stereophotogrammetric analysis (RSA) is used to measure
early prosthetic migration and to predict future implant failure. RSA has several
disadvantages, such as the need for perioperatively inserted tantalum markers.
Therefore, this study evaluates low-field MRI as an alternative to RSA. The use
of traditional MRI with prostheses induces disturbing metal artifacts which are
reduced by low-field MRI. The purpose of this study is to assess the feasibility
to use low-field (0.25 Tesla) MRI for measuring the precision of zero motion.
This was assessed by calculating the virtual prosthetic motion of a zero-motion
prosthetic reconstruction in multiple scanning sessions. Furthermore, the effects
of different registration methods on these virtual motions were tested. RESULTS:
The precision of zero motion for low-field MRI was between 0.584 mm and 1.974 mm
for translation and 0.884 degrees and 3.774 degrees for rotation. The manual
registration method seemed most accurate, with MU <= 0.13 mm (sigma <= 0.931 mm)
for translation and MU <= 0.15 degrees (sigma <= 1.63 degrees ) for rotation.
CONCLUSION: Low-field MRI is not yet as precise as today's golden standard
(marker based RSA) as reported in the literature. However, low-field MRI is
feasible of measuring the relative position of bone and implant with comparable
precision as obtained with marker-free RSA techniques. Of the three registration
methods tested, manual registration was most accurate. Before starting clinical
validation further research is necessary and should focus on improving scan
sequences and registration algorithms.
PMID- 29330711
TI - Boosting tendon repair: interplay of cells, growth factors and scaffold-free and
gel-based carriers.
AB - BACKGROUND: Tendons are dense connective tissues and critical components for the
integrity and function of the musculoskeletal system. Tendons connect bone to
muscle and transmit forces on which locomotion entirely depends. Due to trauma,
overuse and age-related degeneration, many people suffer from acute or chronic
tendon injuries. Owing to their hypovascularity and hypocellularity,
tendinopathies remain a substantial challenge for both clinicians and
researchers. Surgical treatment includes suture or transplantation of autograft,
allograft or xenograft, and these serve as the most common technique for rescuing
tendon injuries. However, the therapeutic efficacies are limited by drawbacks
including inevitable donor site morbidity, poor graft integration, adhesion
formations and high rates of recurrent tearing. This review summarizes the
literature of the past 10 y concerning scaffold-free and gel-based approaches for
treating tendon injuries, with emphasis on specific advantages of such modes of
application, as well as the obtained results regarding in vitro and in vivo
tenogenesis. RESULTS: The search was focused on publications released after 2006
and 83 articles have been analysed. The main results are summarizing and
discussing the clear advantages of scaffold-free and hydrogels carriers that can
be functionalized with cells alone or in combination with growth factors.
CONCLUSION: The improved understanding of tissue resident adult stem cells has
made a significant progress in recent years as well as strategies to steer their
fate toward tendon lineage, with the help of growth factors, have been
identified. The field of tendon tissue engineering is exploring diverse models
spanning from hard scaffolds to gel-based and scaffold-free approaches seeking
easier cell delivery and integration in the site of injury. Still, the field
needs to consider a multifactorial approach that is based on the combination and
fine-tuning of chemical and biomechanical stimuli. Taken together, tendon tissue
engineering has now excellent foundations and enters the period of precision and
translation to models with clinical relevance on which better treatment options
of tendon injuries can be shaped up.
PMID- 29330714
TI - Evidence-Based Recommendations to Improve the Safe Use of Drugs in Patients with
Liver Cirrhosis.
AB - INTRODUCTION: The presence of liver cirrhosis can have a major impact on
pharmacodynamics and pharmacokinetics, but guidance for prescribing is lacking.
OBJECTIVE: The aim of this study is to provide an overview of evidence-based
recommendations developed for the safe use of drugs in liver cirrhosis. METHODS:
Recommendations were based on a systematic literature search combined with expert
opinion from a panel of 10 experts. The safety of each drug was classified as
safe, no additional risks known, additional risks known, unsafe, unknown or the
safety class was dependent on the severity of liver cirrhosis (Child-Pugh
classification). If applicable, drug-specific dosing advice was provided. All
recommendations were implemented in clinical decision support systems and on a
website. RESULTS: We formulated 218 recommendations for a total of 209 drugs. For
nine drugs, two recommendations were formulated for different administration
routes or indications. Drugs were classified as 'safe' in 29 recommendations
(13.3%), 'no additional risks known' in 60 (27.5%), 'additional risks known' in 3
(1.4%), and 'unsafe' in 30 (13.8%). In 57 (26.1%) of the recommendations, safety
depended on the severity of liver cirrhosis and was 'unknown' in 39 (17.9%)
recommendations. Large alterations in pharmacodynamics were the main reason for
classifying a drug as 'unsafe'. For 67 drugs (31%), a dose adjustment was needed.
CONCLUSIONS: Over 200 recommendations were developed for the safe use of drugs in
patients with liver cirrhosis. Implementing these recommendations into clinical
practice can possibly enhance medication safety in this vulnerable patient group.
PMID- 29330715
TI - Case Series Analysis of New Zealand Reports of Rapid Intense Potentiation of
Warfarin by Roxithromycin.
AB - INTRODUCTION: We undertook an analysis of all the reports to the New Zealand
Centre for Adverse Reactions Monitoring of a roxithromycin/warfarin interaction
after two recent reports described intense rapid warfarin potentiation. The
interaction was first published in 1995. Cytochrome P450 3A4 inhibition has been
the proposed mechanism but has limited biologic plausibility. There are
suggestions that the clinical significance of the interaction may be increased by
severe illness, polypharmacy, renal dysfunction, older age and increased warfarin
sensitivity. METHODS: To investigate the potentiating effect of warfarin on
roxithromycin in this New Zealand case series, the reports were reviewed to
identify patients at risk, compare the reporting pattern with published
Australian data and evaluate the appropriateness of current prescribing advice.
RESULTS: Thirty patient reports were identified. The age range was 23-88 years,
mean 66.8, median 73.0 (standard deviation 17.7) and the international normalised
ratios after roxithromycin commencement ranged from 3.6 to 16.7 (mean 7.6, median
7.6, standard deviation 3.6). For eight patients with measurements on day 3,
international normalised ratios were 4.3-16.7 (mean 10.4, median 8.8, standard
deviation 4.4). Four patients had serious haemorrhage. Indications for
roxithromycin were a range of respiratory tract infections. Anticoagulation was
stable for most patients prior to acute infection. Serious infection occurred in
54.5% (12 of 22 patients with information). Polypharmacy (five or more medicines
daily) was used by 36.7% of patients long term, increasing acutely to 83.3%,
including additional potentially interacting medicines. Warfarin daily dose (1.5
13.0 mg, mean 4.4, median 4.0, standard deviation 2.2) was moderate to low. Pre
roxithromycin international normalised ratio values ranged from 1.4 to 3.7, mean
and median 2.5, standard deviation 0.5. A high proportion of interactions were
observed between warfarin and roxithromycin compared with other macrolides and
compared with cytochrome P450 3A4-related macrolide interactions. The pattern was
similar to published Australian data. CONCLUSION: In this case series, the high
prevalence of acute polypharmacy, including potentially interacting medicines,
and serious infection suggests that they may have contributed to warfarin
potentiation and increased the clinical significance of a roxithromycin/warfarin
interaction.
PMID- 29330716
TI - Long-Term Survival of Patients with Thin (T1) Cutaneous Melanomas: A Breslow
Thickness Cut Point of 0.8 mm Separates Higher-Risk and Lower-Risk Tumors.
AB - BACKGROUND: Counterintuitively, more deaths from melanoma occur among patients
with thin (T1) primary melanomas (<= 1 mm) than among those with thick primary
melanoma because the great majority present with T1 tumors. Therefore, it is
important to stratify their risk as accurately as possible to guide their
management and follow-up. This study sought to explore the relationship between
tumor thickness and prognosis for patients with thin primary melanomas. METHODS:
A retrospective, single-institution study investigated 6263 patients with
cutaneous melanoma (including 2117 T1 cases) who had a minimum follow-up period
of 10 years. RESULTS: For the entire patient cohort, the 10-year melanoma
specific survival (MSS) rate ranged between 92% for the patients with primary
melanomas up to 0.3 mm thick and 32% for those with melanomas thicker than 8 mm.
When divided into 25-quantile-thickness groups there was a significant difference
in 10-year MSS between the two consecutive groups 0.8 and 0.9 mm; the differences
in survival were not significantly different for any other consecutive cut points
within the less than or equal to 1 mm thickness range, indicating a biologically
relevant difference in outcome above and below 0.8 mm. For the patients treated
initially at the authors' institution, the 10- and 20-year MSS rates for those
with tumors up to 0.8 mm thick were respectively 93.4 and 85.7%, and for tumors
0.9 to 1.0 mm, the rates were respectively 81.1 and 71.4%. Only 29.3% of the T1
patients who died of melanoma were deceased within 5 years. CONCLUSIONS: A
naturally occurring thickness cut point of 0.8 mm predicts higher or lower risk
for patients with thin primary cutaneous melanomas. Long-term follow-up
assessment of patients with T1 melanoma is important because late mortality due
to melanoma is more common than early mortality.
PMID- 29330717
TI - Posterior Retroperitoneoscopic Resection of Extra-adrenal Paraganglioma Located
in the Aorto-caval Space.
AB - BACKGROUND: The posterior retroperitoneoscopic adrenalec tomy has several
advantages compared with the transperitoneal approach such as a shorter and more
direct route to the target organ, no breach of the intraperitoneal space, and no
required retraction of the adjacent organs. It also is a safe procedure with a
short learning curve.1-5 This report presents a challenging case of an extra
adrenal paraganglioma located in the aorto-caval space and managed using the
retroperitoneal approach. METHODS: A 39-year-old man was placed in the prone
jackknife position, and three incisions were made in the right posterior
abdominal wall for placement of the laparoscopic ports. The retroperitoneal space
was entered with diathermy and blunt finger dissection, and retropneumoperitoneum
was achieved with carbon dioxide insufflation pressure up to 18 mmHg. After
identification of the right kidney and vessels, the tumor was meticulously
dissected and excised with an energy device. The specimen was removed using a
laparoscopic specimen retrieval bag, and the port sites were closed in layers.
RESULTS: The operative time was 130 min, and the total blood loss was 30 ml. The
tumor was diagnosed as a moderately differentiated extra-adrenal paraganglioma.
The Von Hippel-Lindau gene mutation was detected using next-generation
sequencing. CONCLUSIONS: The posterior retroperitoneoscopic approach is a safe,
feasible, and effective method for excising an extra-adrenal paraganglioma even
in the aorto-caval space. The authors suggest that this procedure is a useful
surgical option for treatment of an aorto-caval paraganglioma for selected
patients and by experienced surgeons.
PMID- 29330718
TI - SPECT/CT Adds Distinct Lymph Node Basins and Influences Radiologic Findings and
Surgical Approach for Sentinel Lymph Node Biopsy in Head and Neck Melanoma.
AB - BACKGROUND: Planar lymphoscintigraphy (PL) has a lower detection rate of sentinel
lymph nodes (SLNs) in head and neck melanoma compared with other sites. We
assessed situations when single-photon emission computed tomography/computed
tomography (SPECT/CT) identified nodes not seen by PL. We also evaluated the
impact of SPECT/CT on surgical approach and oncologic outcomes. METHODS: Patients
who underwent SLN biopsy (SLNB) for head and neck melanoma with PL and SPECT/CT
between November 2011 and December 2016 were included. Surgeons and radiologists
completed a real-time survey inquiring about the utility of SPECT/CT. Patients
were divided into two groups: patients with nodal basins identified by both PL
and SPECT/CT ('PL + SPECT/CT'), and patients in whom SPECT/CT identified
additional nodal basins not seen on PL ('SPECT/CT only'). Patient demographics
and long-term outcomes including follow-up duration, recurrence, and survival are
described. RESULTS: In the PL + SPECT/CT group, 73 (61.9%) patients were included
and 45 (38.1%) patients were included in the SPECT/CT-only group. SPECT/CT added
51 basins to those seen on PL, primarily in the supraclavicular region (43.1%).
Eighteen patients had positive node(s) in the PL + SPECT/CT group compared with
two patients in the SPECT/CT-only group. Surgeons reported that 81% of the time,
SPECT/CT influenced the location of incision for SLNB. CONCLUSIONS: SPECT/CT
influences the location of incision and contributes most to identification of
nodes in the supraclavicular region. It also detects additional SLN basins when
compared with PL. Further studies are necessary to determine when these
additional basins require sampling.
PMID- 29330719
TI - Prognostic Value of Tumor-Infiltrating Lymphocyte Density Assessed Using a
Standardized Method Based on Molecular Subtypes and Adjuvant Chemotherapy in
Invasive Breast Cancer.
AB - BACKGROUND: This study investigated the prognostic value of tumor-infiltrating
lymphocyte (TIL) density as determined by molecular subtype and receipt of
adjuvant chemotherapy in invasive breast cancer (IBC). METHODS: Stromal TIL
densities were evaluated in 1489 IBC samples using recommendations proposed by
the International TILs Working Group. Cases were allocated to high- and low-TIL
density groups using a cutoff of 10%. RESULTS: Of the 1489 IBC patients, 427
(28.7%) were assigned to the high-TIL group and 1062 (71.3%) to the low-TIL
group. High TIL density was found to be significantly associated with large tumor
size (p = 0.001), high histologic grade (p < 0.001), and high Ki-67 labeling
index (p < 0.001). Triple-negative and human epidermal growth factor receptor 2
(HER2)-positive subtypes had significantly higher TIL densities than luminal A or
B (HER2-negative) subtypes (p < 0.001). High TIL density was significantly
associated with prolonged disease-free survival (DFS) by univariate (p < 0.001)
and multivariate (p < 0.001) analyses. In the low-TIL-density group, the patients
who did not receive adjuvant chemotherapy showed better DFS (p < 0.001), but no
such survival difference was observed in the high-TIL group (p = 0.222). For the
patients who received adjuvant anthracycline, high-TIL density was found to be an
independent prognostic factor of favorable DFS in the luminal B (HER2-negative; p
= 0.003), HER2-positive (p = 0.019), and triple-negative (p = 0.017) subtypes.
CONCLUSION: Measurements of TIL density in routine clinical practice could give
useful prognostic information for the triple-negative, HER2-positive, and luminal
B (HER2-negative) IBC subtypes, especially for patients administered adjuvant
anthracycline.
PMID- 29330720
TI - Dialysis Increases the Risk of Bladder Recurrence in Patients with Upper Tract
Urothelial Cancer: A Population-Based Study.
AB - BACKGROUND: The relation of dialysis to tumor recurrence in patients with upper
tract urothelial cancer (UTUC) is unknown; however, a limited number of small
scale studies suggest that patients with renal diseases prior to UTUC are more
likely to exhibit bladder recurrence. We performed a population-based analysis to
determine the effect of dialysis on bladder recurrence for patients with UTUC.
METHODS: This retrospective cohort study included patients diagnosed with UTUC
(2002-2007) from the Taiwan National Cancer Registry and divided them into two
groups-dialysis and non-dialysis groups. These patients were followed up until
bladder recurrence, death, or the end of 2010. Competing risk analyses adjusting
covariates and death were applied to determine the relation of dialysis and
bladder recurrence. RESULTS: Of the 5141 eligible patients, 548 (10.7%) were
undergoing dialysis. The cumulative bladder recurrence was significantly higher
in the dialysis group than in the non-dialysis group (29% vs. 21%, modified log
rank p < 0.001). In the multivariable analysis, the dialysis group exhibited a
64% increased bladder recurrence risk (cause-specific hazard ratio 1.64, 95%
confidence interval 1.34-2.01, p < 0.001), which was confirmed using
stratification and propensity score weighting methods. The other prognostic
factors for bladder recurrence were sex, diabetes, cardiac disorder, Charlson
Comorbidity Index, and tumor grade. CONCLUSIONS: Despite unknown reasons,
approximately one-tenth of patients with UTUC have experienced dialysis
treatment. Patients undergoing dialysis have a higher risk of bladder recurrence.
Various treatment and screening strategies should be developed for dialysis and
non-dialysis patients.
PMID- 29330721
TI - Transcriptomic analysis and discovery of genes in the response of Arachis
hypogaea to drought stress.
AB - The peanut (Arachis hypogaea) is an important crop species that is threatened by
drought stress. The genome sequences of peanut, which was officially released in
2016, may help explain the molecular mechanisms that underlie drought tolerance
in this species. We report here a gene expression profiling of A. hypogaea to
gain a global view of its drought resistance. Using whole-transcriptome
sequencing, we analysed differential gene expression in response to drought
stress in the drought-resistant peanut cultivar J11. Pooled samples obtained at
6, 12, 18, 24, and 48 h were compared with control samples at 0 h. In total,
51,554 genes were found, including 49,289 known genes and 2265 unknown genes. We
identified 224 differentially expressed transcription factors, 296,335 SNPs and
28,391 InDELs. In addition, we detected significant differences in the gene
expression profiles of the treatment and control groups. After comparing the two
groups, 4648 genes were identified. An in-depth analysis of the data revealed
that a large number of genes were associated with drought stress, including
transcription factors and genes involved in photosynthesis-antenna proteins,
carbon metabolism and the citrate cycle. The results of this study provide
insights into the diverse mechanisms that underlie the successful establishment
of drought resistance in the peanut, thereby facilitating the identification of
important genes in the peanut related to drought management. Transcriptome
analysis based on RNA-Seq is a powerful approach for gene discovery and molecular
marker development for this species.
PMID- 29330722
TI - Location of low copy genes in chromosomes of Brachiaria spp.
AB - Repetitive DNA sequences have been widely used in cytogenetic analyses. The use
of gene sequences with a low-copy-number, however, is little explored especially
in plants. To date, the karyotype details in Brachiaria spp. are limited to the
location of rDNA sites. The challenge lies in developing new probes based on
incomplete sequencing data for the genus or complete sequencing of related
species, since there are no model species with a sequenced genome in Brachiaria
spp. The present study aimed at the physical location of conserved genes in
chromosomes of Brachiaria ruziziensis, Brachiaria brizantha, and Brachiaria
decumbens using RNAseq data, as well as sequences of Setaria italica and Sorghum
bicolor through the fluorescent in situ hybridization technique. Five out of
approximately 90 selected sequences generated clusters in the chromosomes of the
species of Brachiaria studied. We identified genes in synteny with 5S and 45S
rDNA sites, which contributed to the identification of chromosome pairs carrying
these genes. In some cases, the species of Brachiaria evaluated had syntenic
segments conserved across the chromosomes. The use of genomic sequencing data is
essential for the enhancement of cytogenetic analyses.
PMID- 29330723
TI - Association Between the Incidence of Pancreatic Fistula After
Pancreaticoduodenectomy and the Degree of Pancreatic Fibrosis.
AB - OBJECTIVE: The objective of this study is to investigate the association between
the incidence of pancreatic fistula after pancreaticoduodenectomy (PD) and the
degree of pancreatic fibrosis. METHOD: Between January 2013 and December 2016,
the analysis of the clinical data of 529 cases of pancreaticoduodenectomy
patients of our hospital was performed in a retrospective fashion. The univariate
analysis and multivariate analysis were done using the Pearson chi-squared test
and binary logistic regression analysis model; correlations were analyzed by
Spearman rank correlation analysis. The value of the degree of pancreatic
fibrosis to predict the incidence of pancreatic fistula after
pancreaticoduodenectomy was evaluated by the area under the receiver operating
characteristic (ROC) curve. RESULTS: The total incidence of pancreatic fistula
after pancreaticoduodenectomy was 28.5% (151/529). Univariate analysis and
multivariate analysis showed that BMI >= 25 kg/m2, pancreatic duct size <= 3 mm,
pancreatic CT value< 30, the soft texture of the pancreas (judged during the
operation), and the percent of fibrosis of pancreatic lobule <= 25% are
prognostic factors of pancreatic fistula after pancreaticoduodenectomy (P <
0.05); the pancreatic CT value and the percent of fibrosis of pancreatic lobule
in pancreatic fistula group were both lower than those in non-pancreatic fistula
group (P < 0.05). Results indicated that there is a negative correlation between
the severity of pancreatic fistula and the pancreatic CT value or the percent of
fibrosis of pancreatic lobule (r = - 0.297, - 0.342, respectively). The areas
under the ROC curve of the percent of fibrosis of pancreatic lobule and the
pancreatic CT value were 0.756 and 0.728, respectively. CONCLUSION: The degree of
pancreatic fibrosis is a prognostic factor which can influence the pancreatic
texture and the incidence of pancreatic fistula after pancreaticoduodenectomy.
The pancreatic CT value can be used as a quantitative index of the degree of
pancreatic fibrosis to predict the incidence of pancreatic fistula after
pancreaticoduodenectomy.
PMID- 29330725
TI - Cytologic Diagnosis of Biliary Strictures: FISH or Cut the Sensitivity Rate?
PMID- 29330724
TI - A Novel Nomogram for Predicting Postsurgical Intra-abdominal Infection in Gastric
Cancer Patients: a Prospective Study.
AB - BACKGROUND: This study aimed to determine the relationship between intra
abdominal infection (IAI) and sarcopenia prospectively and to construct a
nomogram to identify patients at a high risk of IAI. METHODS: We conducted a
prospective study of 682 consecutive patients with gastric cancer who underwent
radical gastrectomy. The sarcopenia elements, including lumbar skeletal muscle
index, handgrip strength, and gait speed, were measured before surgery. Factors
contributing to IAI were determined through univariate and multivariate analysis.
A nomogram consisting of the independent risk factors was constructed to quantify
the individual risk of IAI. RESULTS: Of the 682 patients enrolled in this study,
132 patients were diagnosed with sarcopenia and 61 were diagnosed with IAI.
Logistic analysis revealed that sarcopenia, tumor size, pathological type, and
multivisceral resection were independent prognostic factors for IAI. The nomogram
model for IAI was able to reliably quantify the risk of IAI with a strong
optimism-adjusted discrimination (concordance index, 0.736). CONCLUSIONS:
Sarcopenia is an independent predictor of IAI. Our nomogram was a simple and
practical instrument to quantify the individual risk of IAI and could be used to
identify patients at a high risk.
PMID- 29330727
TI - Gastroenterology Fellowship Match: An Inside Look.
PMID- 29330726
TI - Ultra-Deep Genomic Sequencing of HCV NS5A Resistance-Associated Substitutions in
HCV/HIV Coinfected Patients.
AB - BACKGROUND AND AIMS: The prevalence of naturally occurring HCV-NS5A resistance
associated substitutions (RAS) to DAA drugs might affect the response to
treatment in HCV/HIV coinfected subjects. There are limited data on the frequency
of HCV-NS5A naturally occurring drug-RAS at baseline in HCV/HIV coinfected
patients when ultra-deep sequencing methodologies are applied. METHODS: HCV-NS5A
RAS were evaluated among 25 subjects in each group. Patients were matched by age,
gender, and hepatic fibrosis stage category to control for selection bias.
RESULTS: Within subtype 1a, RAS were observed in 28% of HCV monoinfected and 48%
of HCV/HIV coinfected subjects. More patients in the HCV/HIV coinfected group had
clinically relevant mutations to DAA directed at NS5A. CONCLUSION: While the
clinical significance of this observation may be limited in highly drug adherent
populations, some HCV/HIV coinfected persons may be at greater risk of viral
resistance if suboptimal dosing occurs.
PMID- 29330729
TI - Revenge of the NERDs: Cadherin Fragments Differentiate Functional Heartburn from
Non-erosive Reflux Disease.
PMID- 29330728
TI - Analysis of Plasma Tenascin-C in Post-HCV Cirrhosis: A Prospective Study.
AB - BACKGROUND AND AIM: Hepatitis C virus (HCV)-related cirrhosis, one of the most
common etiologies of liver cirrhosis in the Western world, is a risk factor for
hepatocellular carcinoma. To confirm and improve current effectiveness of
screening and prognosis of patients with established cirrhosis, a credible,
simple plasma biomarker is needed. Hepatic stellate cell activation, a pivotal
event in cirrhosis development, results in increased secretion of extracellular
matrix proteins, including tenascin-C (TnC). Herein, we tested TnC as a simple
biomarker to identify cirrhotic patients with active HCV infection from those
with HCV eradication. METHODS: A prospective study of subjects with HCV-related
cirrhosis, stratified into two groups, HCV or virologic cure, was conducted.
Plasma TnC expression was measured by ELISA and Western blots. TnC values were
correlated with markers of liver injury and ROC analyses performed between
groups. RESULTS: The HCV cirrhotic cohort, consisting mostly of men (56%),
Caucasians (76%), and genotype 1a or 1b (84%), was compared to healthy controls
(HCs). Plasma TnC was significantly higher in HCV cirrhotic patients with active
infection compared to HCs (P < 0.0001) and virologic cure (P < 0.0001). TnC
concentrations in virologic cure subjects were not statistically different from
HCs. TnC levels correlated with AST, platelets, MELD, APRI, FIB-4, and Child-Pugh
score. TnC and AST together were significantly better indicators of cirrhosis in
patients with active HCV infection than other markers tested. CONCLUSIONS: TnC
and AST provided the best model for discriminating HCV cirrhotics with active
infection from HC and virologic cure cohorts over current liver injury markers,
suggesting TnC as a potential indicator of ongoing hepatic injury and
inflammation.
PMID- 29330730
TI - Scaffold-free tissue engineering for injured joint surface restoration.
AB - Articular cartilage does not heal spontaneously due to its limited healing
capacity, and thus effective treatments for cartilage injuries has remained
challenging. Since the first report by Brittberg et al. in 1994, autologous
chondrocyte implantation (ACI) has been introduced into the clinic. Recently, as
an alternative for chondrocyte-based therapy, mesenchymal stem cell (MSC)-based
therapy has received considerable research attention because of the relative ease
in handling for tissue harvest, and subsequent cell expansion and
differentiation. In this review, we discuss the latest developments regarding
stem cell-based therapies for cartilage repair, with special focus on recent
scaffold-free approaches.
PMID- 29330731
TI - Human Plant Exposures Reported to a Regional (Southwestern) Poison Control Center
Over 8 Years.
AB - BACKGROUND: There is little published data about human plant exposures reported
to US poison control centers (PCCs). METHODS: A retrospective chart review of all
reported plant exposures to a single regional PCC between January 1, 2003 and
December 31, 2010 was done to understand better the characteristics of plant
exposure cases. Specific generic plant codes were used to identify cases.
Recorded variables included patient demographics, plant involved, exposure
variables, symptoms, management site, treatments, and outcome. Univariate and
multivariate regression was used to identify outcome predictors. RESULTS: A total
of 6492 charts met inclusion criteria. The average age was 16.6 years (2 months
94 years); 52.4% were male. The most common exposure reason was unintentional
(98%), and the majority (92.4%) occurred at the patient's home. Ingestions
(58.3%) and dermal exposures (34.3%) accounted for most cases. Cactus (27.5%),
oleander (12.5%), Lantana (5.7%), and Bougainvillea (3.8%) were most commonly
involved. Symptoms developed in 47.1% of patients, and were more likely to occur
following Datura (66.7%), and Morning Glory or Milkweed (25% each) exposures.
Almost 94% of patients were managed onsite (home) and only 5.2% involved
evaluation in a health care facility (HCF). Only 37 (0.6%) patients required
hospital admission, and 2.9% of cases resulted in more than minimal effects.
Exposures resulting in more than minimal clinical effects were predicted by
several variables: abnormal vital signs (OR = 35.62), abnormal labs (OR = 14.87),
and management at a HCF (OR = 7.37). Hospital admissions were increased for
patients already at a HCF (OR = 54.01), abnormal vital signs (OR = 23.28), and
intentional exposures (OR = 14.7). CONCLUSION: Plant exposures reported to our
poison control center were typically unintentional ingestions occurring at home.
Most patients were managed onsite and few developed significant symptoms.
PMID- 29330732
TI - Touching the Spirit: Re-enchanting the Person in the Body.
AB - In this essay, we argue that touch constitutes a sacred connection between the
patient and practitioner. When touch is avoided or overlooked, the enigmatic
inner workings of the body are ignored as those aspects of the body that can be
quantified and ultimately controlled are emphasized. In utilizing touch as a
fundamental way of opening up space for the sacred, the practitioner affirms the
humanity for both the patient and herself. Only by returning to the senses can
practitioners resist the dehumanizing effects of machinery and re-enchant the
health-care profession in caring for persons they have sworn to serve.
PMID- 29330734
TI - How does School Experience Relate to Adolescent Identity Formation Over Time?
Cross-Lagged Associations between School Engagement, School Burnout and Identity
Processing Styles.
AB - The existing research findings still do not provide a clear understanding of the
links between adolescent school experience and their identity formation. To
address this gap, we analyzed the dynamic links between adolescent school
experiences and identity formation by exploring the cross-lagged associations
between school engagement, school burnout and identity processing styles
(information-oriented, normative and diffuse-avoidant) over a 2-year period
during middle-to-late adolescence. The sample of this school-based study included
916 adolescents (51.4% females) in the 9th to 12th grades from diverse socio
economic and family backgrounds. The results from the cross-lagged analyses with
three time points revealed that (a) school engagement positively predicted
information-oriented identity processing over a 2-year period; (b) school burnout
positively predicted the reliance on normative and diffuse-avoidant identity
styles across the three measurements; (c) the effects were stable over the three
time points and across different gender, grade, and socio-economic status groups.
The unidirectional effects identified in our study support the general prediction
that active engagement in learning at school can serve as a resource for
adolescent identity formation, while school burnout, in contrast, can hinder the
formation of adolescent identity. This points to the importance of taking
developmental identity-related needs of adolescents into account when planning
the school curriculum.
PMID- 29330736
TI - Study on the Multi-level Resistance-Switching Memory and Memory-State-Dependent
Photovoltage in Pt/Nd:SrTiO3 Junctions.
AB - Pt/Nd:SrTiO3 (STO)/In devices were fabricated by depositing Schottky-contact Pt
and Ohmic-contact In electrodes on a single crystal STO with Nd doping. The
Pt/Nd:STO/In devices show multi-level resistance-switching (RS) memory and memory
state-dependent photovoltage (PV) effects, which can be controlled by the applied
pulse width or magnitude. Both the RS and PV are related to the bias-induced
modulation of the interface barrier, both in height and width, at the Pt/Nd:STO
interface. The results establish a strong connection between the RS/PV effects
and the modulation of the Nd:STO interface triggered by applied electric field
and provide a new route by using an open-circuit voltage for non-destructively
sensing multiple non-volatile memory states.
PMID- 29330733
TI - Intergenerational Continuity in Depression: The Importance of Time-Varying
Effects, Maternal Co-morbid Health Risk Behaviors and Child's Gender.
AB - Intergenerational continuity in depressive symptoms is well established between
mother and child, but there are still important facets of this relationship that
are underexplored. We examine intergenerational continuity in depressive symptoms
between mother-child dyads as a flexible function of child age and account for
the potential moderating role of maternal co-morbid health risk behaviors. Using
prospective, self-report data collected yearly from 413 mother-child dyads (210
mother-son dyads and 203 mother-daughter dyads) between child ages 12-17, the
results indicate that the effect of maternal depressive symptoms on daughters'
depressive symptoms steadily increases throughout adolescence whereas the effect
of maternal depressive symptoms on sons' depressive symptoms is relatively small,
stable, and non-significant during mid-adolescence before increasing in effect in
later adolescence. A positive interactive effect between maternal depressive
symptoms and intimate partner violence is observed for sons and maternal
depressive symptoms and substance use for daughters. A negative interactive
effect of maternal depressive symptoms and substance use is observed among sons.
Overall, this study identifies particular subgroups for whom intervention
programming is most beneficial and suggests targeting health risk behaviors of
mothers to lessen the impact of maternal depressive symptoms on offspring.
PMID- 29330737
TI - Letter to the editor.
PMID- 29330738
TI - A video review of multiple concussion signs in National Rugby League match play.
AB - BACKGROUND: Video review has been introduced in many professional sports
worldwide to help recognize concussions. However, to date, there has been very
little research on the accuracy of using video analysis to identify signs of
concussion and the various combinations of observed signs. METHODS: The objective
of the study is to determine the accuracy of combinations of clinical signs of
concussion identified using video analysis to identify concussions in the
National Rugby League (NRL). Incidences of players using of the concussion
interchange rule (CIR) (n = 156), including those where athletes were diagnosed
with a concussion (n = 60), were used to calculate sensitivity and specificity of
various combinations of concussion signs (unresponsiveness, slow to get up,
clutching/shaking head, gait ataxia, vacant stare, and apparent seizure) and
their independent association with an eventual diagnosis of concussion. RESULTS:
Using video analysis, players who were diagnosed with a concussion showed a
significantly greater total number of signs at the time of injury (mean = 3.4, SD
= 1.3) than those who were removed from play but not diagnosed with a concussion
(mean = 3.0, SD = 0.9 signs; p = .046). Players who did not return to play during
the same game demonstrated a significantly greater number of total signs than
those who did return to play in the same game following CIR activation (mean =
3.4, SD = 1.2 versus mean = 2.9, SD = 0.9; p = 0.002). The most common
combination of signs that was observed was clutching/shaking the head and
slowness in getting up (17.3%). The sensitivity of the total number of signs
observed decreased as the number of signs increased (range = 0.13-0.62), while
the specificity increased as more signs were observed (range = 0.29-0.90). Most
of the combinations of different observed signs at the time of potential injury
were highly specific (> 0.80), but not sensitive to an eventual diagnosis of
concussion. When considering all potential predictor variables in a logistic
regression model, anticipating the oncoming collision (OR = 3.92, 95% CI = 1.28
12.03), fewer number of defenders involved in the tackle (OR = 0.58, 95% CI =
0.36-0.92), and the presence of a blank or vacant stare (OR = 2.97, 95% CI = 1.26
7.01) were each significantly associated with concussion diagnoses. CONCLUSIONS:
The use of video review in the NRL is challenging, but being aware of the
combinations of possible concussion signs and the likelihood that various
presentations result in a concussion diagnosis can provide a useful addition to
sideline concussion identification and removal from play decisions.
PMID- 29330739
TI - Patterns and outcomes of prescribing venous thromboembolism prophylaxis in
hospitalized older adults: a retrospective cohort study.
AB - Venous thromboembolism (VTE) is a major cause of morbidity and mortality in the
United States. Hospitalized, medically ill older adults have increased risk;
despite guidelines, data suggest suboptimal pharmacologic prophylaxis rates.
Factors influencing provider prescribing non-compliance are unclear. We aimed to
describe VTE prophylaxis practices and identify risk factors for, and outcomes
of, prescribing non-compliance. A retrospective study was conducted of
hospitalized adults aged >= 75 years, admitted to the medicine service of a large
academic tertiary center from May 1, 2014 to June 30, 2015. The primary outcome
was non-compliance, defined as the absence of an order for VTE prophylaxis for
the duration of hospitalization or an interruption of prophylaxis exceeding 24 h.
Secondary measures included in-hospital mortality, length of stay (LOS), and 30
day readmissions. Of 3751 patients (mean age 84.7 years), 97.6% of charts had
prophylaxis orders; 11.0% showed non-compliance. Pharmacologic prophylaxis was
prescribed in 83.3% of patients and mechanical prophylaxis alone in 14.3%.
Factors associated with non-compliance included: higher body mass index (BMI) (p
= 0.04), myocardial infarction (p = 0.01), congestive heart failure (p = 0.001),
metastatic tumor (p = 0.01). Low mobility was not significantly associated with
compliance. Subcutaneous unfractionated heparin was associated with compliance (p
< 0.0001); warfarin (p < 0.0001), heparin infusion (p < 0.0001) and low-molecular
weight heparin (p < 0.0001) with non-compliance. Non-compliance was associated
with increased mortality (p = 0.01), LOS (p < 0.0001), readmissions (p = 0.0004).
Known VTE risk factors (mobility, BMI, comorbidities) were not associated with
prescriber compliance patterns. Integrating risk assessment models into provider
practice may improve compliance.
PMID- 29330740
TI - 3D reconstruction of dynamic liquid film shape by optical grid deflection method.
AB - In this paper, we describe the optical grid deflection method used to reconstruct
the 3D profile of liquid films deposited by a receding liquid meniscus. This
technique uses the refractive properties of the film surface and is suitable for
liquid thickness from several microns to millimeter. This method works well for
strong interface slopes and changing in time film shape; it applies when the
substrate and fluid media are transparent. The refraction is assumed to be
locally unidirectional. The method is particularly appropriate to follow the
evolution of parameters such as dynamic contact angle, triple liquid-gas-solid
contact line velocity or dewetting ridge thickness.
PMID- 29330741
TI - Coronary artery aneurysm regression after Kawasaki disease and associated risk
factors: a 3-year follow-up study in East China.
AB - Kawasaki disease (KD) is the leading cause of acquired heart disease due to its
complicated coronary artery lesions. Up to now, few studies were focused on the
status of persistent coronary artery aneurysms (CAA) in KD patients. The present
study was designed to identify the coronary artery outcomes and seek the risk
factors associated with the regression of CAA in KD patients. One hundred and
twenty KD patients with CAA hospitalized in Children's Hospital of Soochow
University from Jan 2008 to Dec 2013 were prospectively studied by a 3-year
follow-up. Data regarding demographic, clinical, laboratory, and
echocardiographic characteristics were documented and further analyzed. It was
estimated that 39.2% of the patients had complete regression of CAA within 4
weeks, 59.2% within 8 weeks, and 70.0% within 16 weeks. No fatal cardiac events
occurred. We found patients who aged <= 1 year, received initial intravenous
immunoglobulin (IVIG) treatment after the 10th day of illness, and IVIG non
responders were associated with the regression of persistent CAA. The relative
risks were 1.55, 1.87, and 1.88, respectively. Age, initial IVIG treatment, and
IVIG response were risk factors of persistent CAA, and more attention should be
paid on these patients.
PMID- 29330742
TI - Henoch-Schonlein purpura nephritis: initial risk factors and outcomes in a Latin
American tertiary center.
AB - The objective of this study was to evaluate prevalence, initial risk factors, and
outcomes in Henoch-Schonlein purpura nephritis (HSPN) patients in Latin America.
Two hundred ninety-six patients (validated EULAR/PRINTO/PRES HSP criteria) were
assessed by demographic data, clinical/laboratorial involvements, and treatments
in the first 3 months after diagnosis. They were followed-up in a Latin American
tertiary center and were divided in two groups: with and without nephritis.
Persistent non-nephrotic proteinuria, nephrotic proteinuria, and acute/chronic
kidney injury were also systematically evaluated at 1, 5, 10, and 15 years after
diagnosis. HSPN was evidenced in 139/296 (47%) in the first 3 months. The median
age at diagnosis was significantly higher in HSPN patients compared without renal
involvement [6.6 (1.5-17.7) vs. 5.7 (0.9-13.5) years, p = 0.022]. The frequencies
of persistent purpura (31 vs. 10%, p < 0.0001), recurrent abdominal pain (16 vs.
7%, p = 0.011), gastrointestinal bleeding (25 vs. 10%, p < 0.0001), and
corticosteroid use (54 vs. 41%, p = 0.023) were significantly higher in the
former group. Logistic regression demonstrated that the independent variables
associated with HSNP were persistent purpura (OR = 3.601; 95% CI (1.605-8.079); p
= 0.002) and gastrointestinal bleeding (OR = 2.991; 95% CI (1.245-7.183); p =
0.014). Further analysis of patients without HSPN in the first 3 months revealed
that 29/118 (25%) had persistent non-nephrotic proteinuria and/or hematuria in 1
year, 19/61 (31%) in 5 years, 6/17 (35%) in 10 years and 4/6 (67%) in 15 years
after diagnosis. None of them had chronic kidney injury or were submitted to
renal replacement therapy. The present study observed HSPN in almost one half of
patients in the first months of disease, and HSPN was associated with persistent
purpura and gastrointestinal bleeding. One fourth of patients had nephritis only
evidenced during follow-up without severe renal manifestations.
PMID- 29330743
TI - Acute downregulation of miR-155 leads to a reduced collagen synthesis through
attenuating macrophages inflammatory factor secretion by targeting SHIP1.
AB - Fibrosis, tightly associated with fibroblasts collagen synthesis, is related
closely with inflammatory response. Our previously study found that acute
downregulation of miR-155 at wound sites leads to a reduced fibrosis, however its
particular mechanism is unclear. Herein, we aimed to explore the mechanism of miR
155 in reducing fibrosis. We first found that down-regulation of miR-155
inhibited macrophages transforming growth factor-beta1 (TGF-beta1) and IL-1beta
secretion. Next, we found that co-cultured with macrophages increased the
proliferation and collagen synthesis of fibroblasts, and downregulation of miR
155 in macrophages could effectively attenuate the accelerative effects. We
further identified SH2 domain containing inositol-5-phosphatase 1 (SHIP1) as a
direct target of miR-155 in macrophages, and the expression of SHIP1 was
negatively correlated with the level of miR-155. We further confirmed that
PI3K/Akt pathway was involved in this process. Last, we found that downregulation
of miR-155 leads to a reduced fibrosis in sever burn rat. Taken together, these
results indicate that down-regulation of miR-155 leads to a reduced fibroblasts
proliferation and collagen synthesis through attenuating macrophages TGF-beta1
and IL-1beta secretion by targeting SHIP1 via PI3K/Akt pathway, suggesting its
potential therapeutic effects on the treatment of skin fibrosis.
PMID- 29330744
TI - c-Fos downregulation positively regulates EphA5 expression in a congenital
hypothyroidism rat model.
AB - The EphA5 receptor is well established as an axon guidance molecule during neural
system development and plays an important role in dendritic spine formation and
synaptogenesis. Our previous study has showed that EphA5 is decreased in the
developing brain of congenital hypothyroidism (CH) and the EphA5 promoter
methylation modification participates in its decrease. c-Fos, a well-kown
transcription factor, has been considered in association with brain development.
Bioinformatics analysis showed that the EphA5 promoter region contained five
putative c-fos binding sites. The chromatin immunoprecipitation (ChIP) assays
were used to assess the direct binding of c-fos to the EphA5 promoter.
Furthermore, dual-luciferase assays showed that these three c-fos protein binding
sites were positive regulatory elements for EphA5 expression in PC12 cells.
Moreover, We verified c-fos positively regulation for EphA5 expression in CH
model. Q-PCR and Western blot showed that c-fos overexpression could upregulate
EphA5 expression in hippocampal neurons of rats with CH. Our results suggest that
c-fos positively regulates EphA5 expression in CH rat model.
PMID- 29330745
TI - [Treatment of rotational malalignment of the lower leg].
AB - BACKGROUND: Rotational malalignment after intramedullary nailing of tibial shaft
fractures is not uncommon. In-toeing and out-toeing conditions in children are
often the reason for orthopedic and traumatological medical consultation.
OBJECTIVE: Evaluation of diagnostic modalities and therapeutic options for
rotational malalignment in relationship to the patient's age. Surgical
indications and efficacy of specific surgical techniques. MATERIAL AND METHODS:
Systematic literature search in the German Institute for Medical Documentation
and Information (DIMDI) and MEDLINE and evaluation of the currently published
articles. RESULTS: In adults computed tomography (CT) scanning is the gold
standard for measuring the rotational alignment of the lower leg. To avoid
exposure to ionizing radiation, magnetic resonance imaging (MRI) is currently the
preferred modality in children and adolescents. The indications for corrective
osteotomy are dependent on the functional complaints as well as the rotation
angle measured by CT or MRI. Presently, there is no published study which
demonstrates a correlation between rotation of the lower leg and the development
of arthrosis in the knee or ankle joint. When a rotational osteotomy above the
tibial tubercle is performed, correction of the rotation and the distance between
the tibial tuberosity and the trochlear groove (TT-TG) and therefore
patellofemoral imbalance can be effectively treated. Treatment of rotational
malalignment after tibial shaft fractures is performed by diaphyseal osteotomy
with intramedullary nail stabilization. In children, supramalleolar rotational
osteotomy with subsequent locking plate osteosynthesis or stabilization using
external fixation is performed for torsion correction. CONCLUSION: If there is a
suspicion of rotational malalignment in the lower leg, a CT scan can be performed
in adults and MRI in children and adolescents. Surgical indications for
corrective osteotomy are dependent on functional complaints as well as the CT and
MRI measurements. The CT and MRI reference values are only published according to
the method of Waidelich et al. and Jend et al.
PMID- 29330747
TI - Recent Advances in Screening for Barrett's Esophagus.
AB - OPINION STATEMENT: PURPOSE OF REVIEW: There is a pressing need for effective
strategies to halt the increase in both the incidence and mortality of esophageal
adenocarcinoma (EAC). Screening for Barrett's esophagus, which is the only known
precursor of EAC, remains a ripe area for research, particularly with regard to
identifying the target population, screening tools, and management of screen
detected populations. This review aims to explore in depth the rationale for
screening for Barrett's esophagus, recent biotechnological advances which may
have the potential of making screening feasible, and also highlight the
challenges which will have to be overcome in order make screening for BE a
realistic prospect. RECENT FINDINGS: Imaging techniques such as portable
transnasal endoscopy have the advantage of providing an immediate diagnosis of
Barrett's esophagus as well as other significant pathologies such as reflux
esophagitis and cancer; however, larger studies in non-enriched community
screening populations are required to evaluate their feasibility. The capsule
sponge is a cell-sampling device coupled with a biomarker, which has been most
extensively evaluated with very promising results as regards feasibility,
acceptability, accuracy, and cost-effectiveness. Its effectiveness in increasing
the detection of Barrett's esophagus in primary care is currently being
evaluated. Several Barrett's esophagus risk prediction scores have been developed
with variable degrees of accuracy. Several minimally and non-invasive screening
techniques have been studied including imaging and cell-sampling devices.
Barrett's risk assessment models need to be further validated in independent,
relevant screening populations with clear cut-offs for recommending screening to
be defined.
PMID- 29330748
TI - Surgery in elderly patients with intracranial meningioma: neuropsychological
functioning during a long term follow-up.
AB - Surgical treatment of elderly patients with meningioma is has proved to be safe,
especially when patients are selected using dedicated surgical scores. These
scores take into account tumor size, edema, location and patient's co
morbidities. Neuropsychological functioning (NPF) of this kind of patients has
been poorly studied in literature and it is not taken into account by these
scores. Aim of our study was to describe the long-term outcome in terms of NPF of
elderly patients undergoing surgery. Patients older than 70 years of age affected
by intracranial meningioma and selected with the Clinical-Radiological Grading
Score were included in our study. Neuropsychological testing was performed using
a dedicated battery of tests before surgery, 3 and 12 months after surgery.
Clinical, neurological and radiological outcomes were studied as well. Forty-one
patients with a median age of 74 years were included in this study.
Preoperatively only 1/41 patients showed a normal NPF with all tests scoring
normally. Four out of 39 patients showed a complete neuropsychological recovery
after 3 months; while 10/37 patients had a complete recovery after 12 months. NPF
showed a trend of progressive improvement after surgery. Our study is the first
experience reported in literature describing a long term follow-up in elderly
patients after surgery for intracranial meningioma. In our series, surgery
determined an improvement of NPF over time; especially with a low complication
rate related to the selection of patients obtained through the CRGS. Further
studies need to be performed in order to understand how brain edema, tumor size,
volume and tumor location affect NPF in both short and long term.
PMID- 29330749
TI - Toxicity and efficacy of lomustine and bevacizumab in recurrent glioblastoma
patients.
AB - The combination of lomustine and bevacizumab is a commonly used salvage treatment
for recurrent glioblastoma (GBM). We investigated the toxicity and efficacy of
lomustine plus bevacizumab (lom-bev) in a community-based patient cohort and made
a comparison to another frequently used combination therapy consisting of
irinotecan plus bevacizumab (iri-bev). Seventy patients with recurrent GBM were
treated with lomustine 90 mg/m2 every 6 weeks and bevacizumab 10 mg/kg every 2
weeks. Toxicity was registered and compared to the toxicity observed in 219
recurrent GBM patients who had previously been treated with irinotecan 125 mg/m2
and bevacizumab 10 mg/kg every 2 weeks. The response rate was 37.1% for lom-bev
and 30.1% for iri-bev. Median progression-free survival (PFS) was 23 weeks for
lom-bev and 21 weeks for iri-bev (p = 0.9). Overall survival (OS) was 37 weeks
for lom-bev and 32 weeks for iri-bev (p = 0.5). Lom-bev caused a significantly
higher frequency of thrombocytopenia (11.4% grade 3-4) compared to iri-bev (3.5%
grade 3-4). Iri-bev patients had more gastrointestinal toxicity with regard to
nausea, vomiting, diarrhea, constipation and stomatitis. Within the limitations
of the study lom-bev is a well-tolerated treatment for recurrent GBM, although
hematological toxicity may be a dose limiting factor. No significant differences
between lom-bev and iri-bev were observed with regard to PFS or OS. The
differences in toxicity profiles between lom-bev and iri-bev could guide
treatment decision in recurrent GBM therapy as efficacy is equal and no
predictive factors for efficacy exist.
PMID- 29330746
TI - Risk-stratified therapy for children with FLT3-ITD-positive acute myeloid
leukemia: results from the JPLSG AML-05 study.
AB - Acute myeloid leukemia harboring internal tandem duplication of FMS-like tyrosine
kinase 3 (AMLFLT3-ITD) is associated with poor prognosis. We evaluated the
results of the AML-05 study, in which all AMLFLT3-ITD patients were assigned to
receive hematopoietic stem cell transplantation (HSCT) in the first remission
(1CR). We also investigated the effects of additional genetic alterations on FLT3
ITD. The 5-year overall survival (OS) and event-free survival (EFS) rates among
the 47 AMLFLT3-ITD patients were 42.2 and 36.8%, respectively. The 5-year disease
free survival rate among 29 patients without induction failure was 58.4%. We
defined the allelic ratio (AR) of FLT3-ITD to WT > 0.7 as high. Significant
differences were found in OS (AR-high, 20% vs. AR-low, 66%, p < 0.001) and EFS
(13 vs. 50%, p = 0.004). All five patients with concurrent NPM1 mutations
survived, while seven of eight patients who expressed the NUP98-NSD1 chimera
failed to achieve 1CR and died. Multivariate analysis revealed that AR > 0.7 and
expression of the NUP98-NSD1 chimera strongly impacted OS and EFS. Although all
the AMLFLT3-ITD patients received HSCT at 1CR, the treatment outcome of AMLFLT3
ITD patients did not improve compared with those in a previous study.
Heterogeneity was observed among AMLFLT3-ITD patients.
PMID- 29330750
TI - Immunologic and gene expression profiles of spontaneous canine
oligodendrogliomas.
AB - Malignant glioma (MG), the most common primary brain tumor in adults, is
extremely aggressive and uniformly fatal. Several treatment strategies have shown
significant preclinical promise in murine models of glioma; however, none have
produced meaningful clinical responses in human patients. We hypothesize that
introduction of an additional preclinical animal model better approximating the
complexity of human MG, particularly in interactions with host immune responses,
will bridge the existing gap between these two stages of testing. Here, we
characterize the immunologic landscape and gene expression profiles of
spontaneous canine glioma and evaluate its potential for serving as such a
translational model. RNA in situ hybridization, flowcytometry, and RNA sequencing
were used to evaluate immune cell presence and gene expression in healthy and
glioma-bearing canines. Similar to human MGs, canine gliomas demonstrated
increased intratumoral immune cell infiltration (CD4+, CD8+ and CD4+Foxp3+ T
cells). The peripheral blood of glioma-bearing dogs also contained a relatively
greater proportion of CD4+Foxp3+ regulatory T cells and plasmacytoid dendritic
cells. Tumors were strongly positive for PD-L1 expression and glioma-bearing
animals also possessed a greater proportion of immune cells expressing the immune
checkpoint receptors CTLA-4 and PD-1. Analysis of differentially expressed genes
in our canine populations revealed several genetic changes paralleling those
known to occur in human disease. Naturally occurring canine glioma has many
characteristics closely resembling human disease, particularly with respect to
genetic dysregulation and host immune responses to tumors, supporting its use as
a translational model in the preclinical testing of prospective anti-glioma
therapies proven successful in murine studies.
PMID- 29330751
TI - Prospective trial evaluating the sensitivity and specificity of 3,4-dihydroxy-6
[18F]-fluoro-L-phenylalanine (18F-DOPA) PET and MRI in patients with recurrent
gliomas.
AB - Treatment-related changes can be difficult to differentiate from progressive
glioma using MRI with contrast (CE). The purpose of this study is to compare the
sensitivity and specificity of 18F-DOPA-PET and MRI in patients with recurrent
glioma. Thirteen patients with MRI findings suspicious for recurrent glioma were
prospectively enrolled and underwent 18F-DOPA-PET and MRI for neurosurgical
planning. Stereotactic biopsies were obtained from regions of concordant and
discordant PET and MRI CE, all within regions of T2/FLAIR signal hyperintensity.
The sensitivity and specificity of 18F-DOPA-PET and CE were calculated based on
histopathologic analysis. Receiver operating characteristic curve analysis
revealed optimal tumor to normal (T/N) and SUVmax thresholds. In the 37 specimens
obtained, 51% exhibited MRI contrast enhancement (M+) and 78% demonstrated 18F
DOPA-PET avidity (P+). Imaging characteristics included M-P- in 16%, M-P+ in 32%,
M+P+ in 46% and M+P- in 5%. Histopathologic review of biopsies revealed grade II
components in 16%, grade III in 43%, grade IV in 30% and no tumor in 11%. MRI CE
sensitivity for recurrent tumor was 52% and specificity was 50%. PET sensitivity
for tumor was 82% and specificity was 50%. A T/N threshold > 2.0 altered
sensitivity to 76% and specificity to 100% and SUVmax > 1.36 improved sensitivity
and specificity to 94 and 75%, respectively. 18F-DOPA-PET can provide increased
sensitivity and specificity compared with MRI CE for visualizing the spatial
distribution of recurrent gliomas. Future studies will incorporate 18F-DOPA-PET
into re-irradiation target volume delineation for RT planning.
PMID- 29330752
TI - Evaluation of the iron regulatory protein-1 interactome.
AB - The interactions of iron regulatory proteins (IRPs) with mRNAs containing an iron
responsive element (IRE) is a major means through which intracellular iron
homeostasis is maintained and integrated with cellular function. Although IRE-IRP
interactions have been proposed to modulate the expression of a diverse number of
mRNAs, a transcriptome analysis of the interactions that form within the native
mRNA structure and cellular environment has not previously been described. An RNA
CLIP study is described here that identified IRP-1 interactions occurring within
a primary cell line expressing physiologically relevant amounts of mRNA and
protein. The study suggests that only a small subset of the previously proposed
IREs interact with IRP-1 in situ. Identifying authentic IRP interactions is not
only important to a greater understanding of iron homeostasis and its integration
with cell biology but also to the development of novel therapeutics that can
compensate for iron imbalances.
PMID- 29330753
TI - Transfer of critically ill adults-assessing the need for training.
AB - BACKGROUND: Transfer of critically ill patients within the hospital is commonly
associated with adverse incidents, but, despite this, no standardised training
exists on how to carry out this task. Very little information is published in the
literature on the learning needs of staff undertaking these transfers, and this
limits our ability to provide a focused and appropriate educational intervention.
AIMS: This study aimed to explore the organisational, environmental and
individual issues that increase risk to patients during intrahospital transport
(IHT) and to explore the potential educational solutions to these issues as
articulated by these practitioners. METHODS: This qualitative descriptive study
was conducted in an Irish tertiary hospital critical care unit. Semi-structured
interviews were conducted on critical care practitioners until data saturation
was achieved. After manual transcription of the data, they were then analysed to
identify themes. RESULTS: Two themes emerged: challenges related to intrahospital
transport and plans to improve intrahospital transport. CONCLUSIONS:
Organisational, communication and individual issues need to be considered when
addressing problems associated with IHT. A multifaceted approach is needed, with
a focus on organisational solutions in the form of checklists as well as
educational interventions such as interprofessional education initiatives.
Further studies on implementation of educational initiatives will add to the
findings we report here.
PMID- 29330754
TI - Systematic Review of Mammography Screening Educational Interventions for Hispanic
Women in the United States.
AB - In the United States (U.S.), Hispanics experience breast cancer disparities.
Breast cancer is the leading cause of cancer-related death among Hispanic women,
and Hispanic women receive mammography screening at lower rates than some other
ethnic groups. This low rate of screening mammography is associated with
increased risk for possible late-stage diagnosis and lower survival rates.
Educational interventions could play a role in increasing screening mammography
rates among Hispanic women. This systematic review synthesized the current
literature on educational interventions to increase mammography screening among
Hispanic women. The review included studies published between May 2003 and
September 2017 with experimental and quasi-experimental interventions to increase
mammography screening among Hispanics in the U.S. Five studies out of an initial
269 studies met inclusion criteria for the review. All studies employed an
interpersonal intervention strategy with community health workers, or promotoras,
to deliver the mammography screening intervention. For each study, odds ratios
(OR) were calculated to estimate intervention effectiveness based on similar
follow-up time periods. The study ORs resulted in a narrow range between 1.02 and
2.18, indicating a low to moderate intervention effect for these types of
interpersonal cancer education interventions. The summary OR for the random
effects model was 1.67 (CI 1.24-2.26). Hispanics exhibit lower levels of
adherence to screening mammography than non-Hispanic whites. Interpersonal cancer
education interventions such as the use of promotoras may help to mediate the
impact of barriers to receiving a mammogram such as low health literacy, deficits
in knowledge about the benefits of screening, and low awareness of the
availability of screening services.
PMID- 29330755
TI - [Lymphoma in rheumatic diseases].
AB - Various systemic inflammatory diseases, such as rheumatoid arthritis (RA),
Sjogren's syndrome and systemic lupus erythematosus (SLE) are associated with an
increased risk for the development of lymphomas. Studies on patients with RA and
Sjogren's syndrome have shown that there is a clear association of the incidence
of lymphoma with the severity and activity of the disease and lymphomas in
particular are diseases which preferentially occur in immunosuppressed patients;
therefore, knowledge of the different lymphoma subtypes, their prognosis and
treatment options are important for rheumatologists. Currently, there is no
evidence for an increased risk of lymphoma with the available conventional basis
therapies or biologic disease-modifying antirheumatic drugs (DMARDs). The
decision on how to treat a patient with previous lymphoma who requires
antirheumatic treatment is more difficult as patients with previous malignancies
are not included in clinical studies and in registries a bias with respect to
patient selection must be taken into consideration. Decisions on the treatment
approach, therefore need to be individualized and interdisciplinary management
together with the treating hematologist is warranted.
PMID- 29330756
TI - [Rheumatoid symptoms in patients with hematologic neoplasms].
AB - Paraneoplastic syndromes in lymphatic or myeloid neoplasms can present with
musculoskeletal symptoms, vasculitis-like or febrile symptoms. Hematologic
diseases are also associated with rheumatic diseases whereas inflammatory
rheumatic diseases are often associated with an increased risk for
lymphoproliferative disease. Atypical disease characteristics, lack of disease
specific antibodies or therapeutic response are red flags for diagnosing
paraneoplastic or coexistent malignant diseases. New onset of systemic symptoms,
worsening of general condition, night sweats or weight loss need to be considered
during follow-up and differential diagnostics. This article focuses on
musculoskeletal, vasculitis-like and systemic signs of lymphatic or myeloid
neoplasms either because of coexistency, tumor association or paraneoplastic
disease.
PMID- 29330757
TI - [Myelodysplastic syndrome, acute leukemia and stem cell transplantation].
AB - Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal
hematopoietic stem cell disorders. They are characterized by inefficient
hematopoiesis leading to peripheral cytopenia of one or more lineages and a
variable risk of transformation into acute myeloid leukemia. They may either
arise de novo as well as following exposition to environmental toxins, previous
radiotherapy or chemotherapy or in the context of autoinflammatory diseases and
related therapy. Characteristic cytogenetic abnormalities, along with the numbers
of hematopoietic lineages affected and bone marrow blasts, enable an assessment
of the risk of leukemic transformation. Acute leukemias are characterized by an
accumulation of immature myeloid or lymphatic progenitor cells with limited
differentiation capacity in the bone marrow. Proliferation of blast cells leads
to suppression of normal hematopoiesis resulting in peripheral pancytopenia or
leukocytosis associated with anemia and thrombocytopenia. Acute leukemias
following MDS are defined as high-risk diseases. Intensive induction therapy
followed by allogeneic stem cell transplantation is currently regarded as the
only potentially curative treatment strategy. In this article the basic aspects
of current diagnostics and treatment strategies for MDS and acute leukemia are
outlined. Because of similarities with rheumatic inflammatory diseases,
manifestations and treatment of graft versus host disease (GvHD) are also
included.
PMID- 29330758
TI - [Monoclonal gammopathy of undetermined significance and multiple myeloma].
AB - In rheumatological practice monoclonal gammopathy of undetermined significance
(MGUS) is a common incidental finding. Several rheumatic inflammatory diseases
are known to have an elevated risk of MGUS, which can evolve into multiple
myeloma or other lymphatic malignancies. The relevant definitions of disease
entities are described, as well as algorithms for further diagnostic work-up and
follow-up for monoclonal gammopathy, depending on the risk of progression.
Therapeutic strategies against multiple myeloma are presented. Some of these
therapeutic modalities could play a future role in treating plasma cell-dominated
autoimmune diseases.
PMID- 29330759
TI - [Autoimmune reactions to immune checkpoint inhibitors].
AB - Immune checkpoint inhibitors (ICI) have dramatically changed the face of cancer
treatment and are gaining in importance. The ICIs have now been approved for the
treatment of advanced cancers, including melanoma, non-small-cell and small cell
lung cancers, renal cell carcinoma, Hodgkin's lymphoma, head and neck cancers and
urothelial carcinoma and further indications are to be expected. The organs most
affected by an autoimmune reaction are the intestines, the musculoskeletal
system, skin, endocrine organs, the liver and the lungs. As the indications for
immune checkpoint blockade expand and ICIs are used in combination, it becomes
increasingly more important for rheumatologists to recognize immune-related
adverse events (irAEs), their connection to cancer immunotherapy and how to treat
these events appropriately. The role of rheumatologists will take on growing
importance as immunotherapies become more common as standard treatment of cancer
and when used earlier in the course of the disease. Previously controlled
autoimmune diseases can deteriorate when using ICIs, so this is a consideration
when evaluating patients. Increased awareness of inflammatory arthritis, as well
as other rheumatic manifestations as an adverse association with cancer
immunotherapies, is imperative for making the diagnosis. Treatment algorithms are
based on the severity of symptoms but in the case of rheumatic disease, treatment
often needs to be tailored to the individual. The general strategy for evaluation
and management of irAEs includes a thorough evaluation for infections. Mild irAE
may be self-limiting, while more severe reactions are generally steroid
responsive, albeit with potentially high dosage requirements.
PMID- 29330761
TI - Correction to: Scientific white paper on concentration-QTc modeling.
AB - The original version of this article unfortunately contained an error in Equation
1 under the section "Pre-specified linear mixed effects model". The correct
equation has given below.
PMID- 29330760
TI - Oxidized phospholipids stimulate production of stem cell factor via NRF2
dependent mechanisms.
AB - Receptor tyrosine kinase c-Kit and its ligand stem cell factor (SCF) regulate
resident vascular wall cells and recruit circulating progenitors. We tested
whether SCF may be induced by oxidized palmitoyl-arachidonoyl-phosphatidylcholine
(OxPAPC) known to accumulate in atherosclerotic vessels. Gene expression analysis
demonstrated OxPAPC-induced upregulation of SCF mRNA and protein in different
types of endothelial cells (ECs). Elevated levels of SCF mRNA were observed in
aortas of ApoE-/- knockout mice. ECs produced biologically active SCF because
conditioned medium from OxPAPC-treated cells stimulated activation
(phosphorylation) of c-Kit in naive ECs. Induction of SCF by OxPAPC was inhibited
by knocking down transcription factor NRF2. Inhibition or stimulation of NRF2 by
pharmacological or molecular tools induced corresponding changes in SCF
expression. Finally, we observed decreased levels of SCF mRNA in aortas of NRF2
knockout mice. We characterize OxPLs as a novel pathology-associated stimulus
inducing expression of SCF in endothelial cells. Furthermore, our data point to
transcription factor NRF2 as a major mediator of OxPL-induced upregulation of
SCF. This mechanism may represent one of the facets of pleiotropic action of NRF2
in vascular wall.
PMID- 29330762
TI - How honest are the signals? A protocol for validating wearable sensors.
AB - There is growing interest among organizational researchers in tapping into
alternative sources of data beyond self-reports to provide a new avenue for
measuring behavioral constructs. Use of alternative data sources such as wearable
sensors is necessary for developing theory and enhancing organizational practice.
Although wearable sensors are now commercially available, the veracity of the
data they capture is largely unknown and mostly based on manufacturers' claims.
The goal of this research is to test the validity and reliability of data
captured by one such wearable badge (by Humanyze) in the context of structured
meetings where all individuals wear a badge for the duration of the encounter. We
developed a series of studies, each targeting a specific sensor of this badge
that is relevant for structured meetings, and we make specific recommendations
for badge data usage based on our validation results. We have incorporated the
insights from our studies on a website that researchers can use to conduct
validation tests for their badges, upload their data, and assess the validity of
the data. We discuss this website in the corresponding studies.
PMID- 29330764
TI - The failing measurement of attitudes: How semantic determinants of individual
survey responses come to replace measures of attitude strength.
AB - The traditional understanding of data from Likert scales is that the
quantifications involved result from measures of attitude strength. Applying a
recently proposed semantic theory of survey response, we claim that survey
responses tap two different sources: a mixture of attitudes plus the semantic
structure of the survey. Exploring the degree to which individual responses are
influenced by semantics, we hypothesized that in many cases, information about
attitude strength is actually filtered out as noise in the commonly used
correlation matrix. We developed a procedure to separate the semantic influence
from attitude strength in individual response patterns, and compared these
results to, respectively, the observed sample correlation matrices and the
semantic similarity structures arising from text analysis algorithms. This was
done with four datasets, comprising a total of 7,787 subjects and 27,461,502
observed item pair responses. As we argued, attitude strength seemed to account
for much information about the individual respondents. However, this information
did not seem to carry over into the observed sample correlation matrices, which
instead converged around the semantic structures offered by the survey items.
This is potentially disturbing for the traditional understanding of what survey
data represent. We argue that this approach contributes to a better understanding
of the cognitive processes involved in survey responses. In turn, this could help
us make better use of the data that such methods provide.
PMID- 29330763
TI - Safe and sensible preprocessing and baseline correction of pupil-size data.
AB - Measurement of pupil size (pupillometry) has recently gained renewed interest
from psychologists, but there is little agreement on how pupil-size data is best
analyzed. Here we focus on one aspect of pupillometric analyses: baseline
correction, i.e., analyzing changes in pupil size relative to a baseline period.
Baseline correction is useful in experiments that investigate the effect of some
experimental manipulation on pupil size. In such experiments, baseline correction
improves statistical power by taking into account random fluctuations in pupil
size over time. However, we show that baseline correction can also distort data
if unrealistically small pupil sizes are recorded during the baseline period,
which can easily occur due to eye blinks, data loss, or other distortions.
Divisive baseline correction (corrected pupil size = pupil size/baseline) is
affected more strongly by such distortions than subtractive baseline correction
(corrected pupil size = pupil size - baseline). We discuss the role of baseline
correction as a part of preprocessing of pupillometric data, and make five
recommendations: (1) before baseline correction, perform data preprocessing to
mark missing and invalid data, but assume that some distortions will remain in
the data; (2) use subtractive baseline correction; (3) visually compare your
corrected and uncorrected data; (4) be wary of pupil-size effects that emerge
faster than the latency of the pupillary response allows (within +/-220 ms after
the manipulation that induces the effect); and (5) remove trials on which
baseline pupil size is unrealistically small (indicative of blinks and other
distortions).
PMID- 29330766
TI - Simulaaneous ethanol and cellobiose inhibition of cellulose hydrolysis studied
with integrated equations assuming constant or variable substrate concentration.
AB - The integrated forms of the Michaelis-Menten equation assuming variable substrate
(depletion) or constant substrate concentration were used to study the effect of
the simultaneous presence of two exoglucanase Cel7A inhibitors (cellobiose and
ethanol) on the kinetics of cellulose hydrolysis. The kinetic parameters
obtained, assuming constant substrate (K m =21 mM, K ic =0.035 mM; K icl
=1.5*1015mM; kcat=12 h-1) or assuming variable substrate (K m =16 mM, K ic =0.037
mM; K icl =5.8*1014 mM; kcat=9 h-1), showed a good similarity between these two
alternative methodologies and pointed out that bothethanol and cellobiose are
competitive inhibitors. Nevertheless, ethanol is a very weak inhibitor, as shown
by the large value estimated for the kinetic constant K icl . In addition,
assuming different concentrations of initial accessible substrate present in the
reaction, both inhibition and velocity constants are at the same order of
magnitude, which is consistent with the obtained values. The possibility of using
this kind of methodology to determine kinetic constants in general kinetic
studies is discussed, and several integrated equations of different Michaelis
Menten kinetic models are presented. Also examined is the possibility of
determining inhibition constants without knowledge of the true accessible
substrate concentration.
PMID- 29330765
TI - Pudendal nerve terminal motor latency testing does not provide useful information
in guiding therapy for fecal incontinence.
AB - PURPOSE: Pudendal nerve terminal motor latency (PNTML) testing is a standard
recommendation for the evaluation of fecal incontinence. Its role in guiding
therapy for fecal incontinence has been previously questioned. The aim of this
study was to evaluate the relationship between PNTML testing and anorectal
dysfunction. METHODS: This was a retrospective analysis of data collected
prospectively from patients who presented to a pelvic floor disorder center from
2007 to 2015. The relationship between PNTML (normal versus delayed) and
anorectal manometry, fecal incontinence severity, and fecal incontinence-related
quality of life scores was assessed using the Wilcoxon-Mann-Whitney test.
RESULTS: Two hundred sixty-nine patients underwent PNTML testing, and 91.1% were
female (N = 245) (median age 62.2 years). Normal PNTML was seen in 234 (87.0%)
patients. Among 268 patients who underwent anorectal manometry, delayed PNTML was
only significantly associated with median maximum anal squeeze pressure (P =
0.04). Delayed PNTML was not associated with a decrease in median fecal
incontinence severity or fecal incontinence-related quality of life scores (N =
99). CONCLUSIONS: PNTML was only associated with median maximum anal squeeze
pressure, and it was not associated with patient-reported severity of symptoms of
fecal incontinence, changes in quality of life attributable to fecal
incontinence, median mean resting anal pressure, or median maximum resting anal
pressure. PNTML testing may not be relevant to current therapeutic algorithms for
fecal incontinence and its routine use should be questioned.
PMID- 29330767
TI - Ivabradine for the Treatment of Postural Orthostatic Tachycardia Syndrome: A
Systematic Review.
AB - INTRODUCTION: Postural orthostatic tachycardia syndrome (POTS) impacts millions
of patients, but there is currently no gold standard treatment for this
condition. Ivabradine is a novel heart rate (HR) lowering agent that acts on the
sinoatrial node cells by selectively inhibiting the If-current. OBJECTIVE: The
objective of this systematic review is to evaluate the evidence for the efficacy
and safety of ivabradine for the treatment of POTS. METHODS: MEDLINE (from 1956
to August 2017) and EMBASE (from 1957 to August 2017) were queried with the
following search term: "postural orthostatic tachycardia syndrome" OR "postural
tachycardia syndrome" OR "chronic orthostatic intolerance" AND "ivabradine."
Articles in English with clinical outcomes of human patient(s) treated with
ivabradine for POTS were included. RESULTS: The initial search identified 73
articles. After screening, 13 articles were included. Two prospective open-label
trials, three retrospective cohort studies, and eight case reports evaluated the
safety and efficacy of ivabradine in a total of 132 patients with postural
tachycardia. Overall, ivabradine lowered HR and provided symptomatic relief of
POTS without blood pressure lowering. Dizziness, nausea, headache, and fatigue
were the most common side effects and often did not lead to discontinuation of
treatment. CONCLUSION: Based on this small sample, ivabradine appears to be a
reasonable option for patients with POTS who have failed or are unable to
tolerate other treatment options, however, but a randomized controlled trial in
this population is needed.
PMID- 29330768
TI - Comorbid insomnia symptoms predict lower 6-month adherence to CPAP in US veterans
with obstructive sleep apnea.
AB - PURPOSE: There is limited information on the association between pre-treatment
insomnia symptoms and dysfunctional sleep beliefs with continuous positive airway
pressure (CPAP) adherence in veterans with obstructive sleep apnea (OSA). Our
aims were to describe demographic and sleep characteristics of veterans with and
without comorbid insomnia and determine whether pre-treatment insomnia symptoms
and dysfunctional sleep beliefs predict CPAP use after 6 months of therapy.
METHODS: Hispanic veterans attending the Miami VA sleep clinic were recruited and
completed the insomnia severity index, the dysfunctional sleep belief and
attitude scale (DBAS), and other questionnaires. Participants were asked to
return after 7 days and 1 and 6 months to repeat questionnaires and for objective
CPAP adherence download. Hierarchical regression models were performed to
determine adjusted associations of pre-treatment insomnia symptoms and DBAS sub
scores on 6-month mean daily CPAP use. RESULTS: Fifty-three participants
completed the 6-month follow-up visit with a mean CPAP use of 3.4 +/- 1.9 h.
Veterans with comorbid insomnia had lower mean daily CPAP use (168 +/- 125 vs 237
+/- 108 min, p = 0.04) and lower percent daily CPAP use >= 4 h (32 +/- 32 vs 51
+/- 32%, p = 0.05) compared to participants without insomnia. In adjusted
analyses, pre-treatment insomnia symptoms (early, late, and aggregated nocturnal
symptoms) and sleep dissatisfaction were predictive of lower CPAP use at 6
months. Pre-treatment dysfunctional sleep beliefs were not associated with CPAP
adherence. CONCLUSIONS: Pre-treatment nocturnal insomnia symptoms and sleep
dissatisfaction predicted poorer 6- month CPAP use. Insomnia treatment preceding
or concurrent with CPAP initiation may eliminate a barrier to regular use.
PMID- 29330769
TI - Comorbid insomnia and sleep apnea in Veterans with post-traumatic stress
disorder.
AB - PURPOSE: The purpose of this study was to determine the impact of insomnia in
Veterans with post-traumatic stress disorder (PTSD) and obstructive sleep apnea
(OSA) on health-related outcomes before and after 12 weeks of continuous positive
airway pressure (CPAP) treatment. METHODS: We conducted a prospective cohort
study of Veterans with PTSD and documented apnea hypopnea index (AHI) >= 5 with
and without clinically significant insomnia as determined by the Insomnia
Severity Index (ISI). Health-related outcomes including PTSD checklist (PCL-M),
SF-36, and Pittsburgh Sleep Quality Index (PSQI) were assessed at baseline and 12
weeks after initiation of OSA treatment. CPAP adherence was retrieved at each
visit. RESULTS: Seventy-two Veterans including 36 with comorbid insomnia and OSA
(COMISA) and 36 OSA-only were enrolled. Veterans with COMISA were younger (p =
0.03), had lower BMI (p < 0.001), and were more likely to report depression than
those with OSA-only (p = 0.004). Although AHI was higher in the COMISA (p =
0.01), both groups expressed comparable daytime sleepiness (p = 0.16). The COMISA
group had no significant change in SF-36 and PSQI after 12 weeks of treatment and
used CPAP much less frequently than OSA-only group (p = 0.001). CONCLUSIONS:
COMISA in Veterans with PTSD is associated with worse quality of life than those
with OSA-only. Insomnia should be assessed in Veterans with PTSD who are not
adherent to CPAP treatment.
PMID- 29330770
TI - Decoding Selection Bias Imparted by Unpaired Cysteines: a Tug of War Between
Expression and Affinity.
AB - In a recombinant antibody scFv format, the presence of an unpaired cysteine (Cys)
is implicated in reduced soluble expression and inefficient presentation in phage
display. Compared to other species, antibodies derived from rabbits are more
likely to contain this unpaired Cys residue at position 80 (Cys80), when
generated in a scFv format. In a screening campaign to isolate rabbit scFv
against cardiac troponin I (cTnI), it was found that, a large proportion of
isolated cTnI-specific clones contained unpaired Cys80. To analyze the factors
that led to the selection of anti-cTnI Cys80 scFv, after five rounds of
biopanning, the biopanning experiments were repeated with a Cys80 scFv (MG4Cys),
its alanine variant (MG4Ala), and an irrelevant high expressing scFv control. It
was found that the selection and subsequent enrichment of MG4Cys scFv was ousted
by the superior expressing variant MG4Ala, indicating that the Cys80 scFv was
selected primarily due to its affinity. It is evident that phage-based selection
is influenced by specific sequence characteristics affecting the expression as
well as the binding specificity and this needs to be taken into account for
selection of optimal antibody derivatives.
PMID- 29330771
TI - Inhibition of Human Immunodeficiency Type 1 Virus (HIV-1) Life Cycle by Different
Egg White Lysozymes.
AB - Lysozyme is a relatively small enzyme with different biological activities, which
is found in tears, saliva, egg white, and human milk. In the study, the anti-HIV
1 activity of lysozymes purified from quail, Meleagris, and hen egg white has
been determined. For this end, a time-of-drug-addition assay was performed to
identify the target of anti-HIV-1 agents and for determination of probable anti
HIV-1 mechanism of the studied lysozyme, the binding affinity of the lysozymes to
the human CD4 receptor was studied by molecular docking method. To define
structural differences between studied lysozymes, structural motifs of them were
predicted by MEME tool. Quail, hen, and Meleagris lysozymes showed potent anti
HIV-1 activity with EC50 of 7.5, 10, and 55 nM, respectively. The time-of-drug
addition study demonstrated that the inhibitory effect of all purified lysozymes
is before HIV-1 infection. The frequency and intensity of CD4 expression in PBMCs
decreased in the presence of all mentioned lysozymes. Also, the expression level
of C-C chemokine receptor type 5 (CCR5) and chemokine receptor type 4 (CXCR4) on
CD4+ T cells was not changed in cells treated with these lysozymes. The results
of in silico study confirmed that the binding energy of quail lysozyme with CD4
was more than that of other studied lysozymes. The results revealed that these
lysozymes restrict HIV-1 attachment to host cell CD4.
PMID- 29330772
TI - Rice WRKY11 Plays a Role in Pathogen Defense and Drought Tolerance.
AB - BACKGROUND: Plants are frequently subjected to abiotic and biotic stresses, and
WRKY proteins play a pivotal role in the response to such stress. OsWRKY11 is
induced by pathogens, drought, and heat, suggesting a function in biotic and
abiotic stress responses. RESULTS: This study identified OsWRKY11, a member of
WRKY group IIc. It is a transcriptional activator that localized to the nucleus.
Ectopic expression of OsWRKY11 resulted in enhanced resistance to a bacterial
pathogen, Xanthomonas oryzae pv. oryzae; resistance was compromised in transgenic
lines under-expressing OsWRKY11. Ectopic expression of OsWRKY11 resulted in
constitutive expression of defense-associated genes, whereas knock-down (kd) of
OsWRKY11 reduced expression of defense-associated genes during pathogen attack,
suggesting that OsWRKY11 activates defense responses. OsWRKY11 bound directly to
the promoter of CHITINASE 2, a gene associated with defense, and activated its
transcription. In addition, ectopic expression of OsWRKY11 enhanced tolerance to
drought stress and induced constitutive expression of drought-responsive genes.
Induction of drought-responsive genes was compromised in OsWRKY11-kd plants.
OsWRKY11 also bound directly to the promoter of a drought-responsive gene, RAB21,
activating its transcription. In addition, OsWRKY11 protein levels were
controlled by the ubiquitin-proteasome system. CONCLUSION: OsWRKY11 integrates
plant responses to pathogens and abiotic stresses by positively modulating the
expression of biotic and abiotic stress-related genes.
PMID- 29330774
TI - A collection of XY female cell lines.
AB - Discordance between sexual phenotype and the 46,XY sex chromosome complement may
be found in certain disorders of sexual development (DSD). Many of these DSD
patients with female external genitalia and secondary sex characteristics have
undescended testes and male internal genitalia. Causative mutations involving
genes of the sex determining pathway, including the androgen receptor, SRY and
the 5-alpha-reductase genes, are well-known, but the origin of other cases remain
unresolved. In this report, we introduce our collection of lymphoblastoid lines
derived from female patients with a 46,XY karyotype. These cell lines have been
deposited and registered with the JCRB Cell Bank. They are available for
comparison with other DSD cases and for further characterization of genetic loci
involved in the mammalian sex determining pathway.
PMID- 29330773
TI - Mechanistic regulation of epithelial-to-mesenchymal transition through RAS
signaling pathway and therapeutic implications in human cancer.
AB - RAS effector signaling instead of being simple, unidirectional and linear
cascade, is actually recognized as highly complex and dynamic signaling network.
RAF-MEK-ERK cascade, being at the center of complex signaling network, links to
multiple scaffold proteins through feed forward and feedback mechanisms and
dynamically regulate tumor initiation and progression. Three isoforms of Ras
harbor mutations in a cell and tissue specific manner. Besides mutations, their
epigenetic silencing also attributes them to exhibit oncogenic activities. Recent
evidences support the functions of RAS oncoproteins in the acquisition of tumor
cells with Epithelial-to-mesenchymal transition (EMT) features/ epithelial
plasticity, enhanced metastatic potential and poor patient survival. Google
Scholar electronic databases and PubMed were searched for original papers and
reviews available till date to collect information on stimulation of EMT core
inducers in a Ras driven cancer and their regulation in metastatic spread.
Improved understanding of the mechanistic basis of regulatory interactions of
microRNAs (miRs) and EMT by reprogramming the expression of targets in Ras
activated cancer, may help in designing effective anticancer therapies. Apparent
lack of adverse events associated with the delivery of miRs and tissue response
make 'drug target miRNA' an ideal therapeutic tool to achieve progression free
clinical response.
PMID- 29330777
TI - Focus on Novel Instrumentation in Mass Spectrometry and Ion Mobility
Spectrometry.
PMID- 29330775
TI - A PEG-based method for the isolation of urinary exosomes and its application in
renal fibrosis diagnostics using cargo miR-29c and miR-21 analysis.
AB - PURPOSE: To assess a new and highly specific, but low-cost, easily performed and
suitable for large-scale applications method for renal fibrosis (RF) diagnostics.
METHODS: Thirty-five RF and twenty non-RF patients were enrolled in the study. An
appropriate polyethylene glycol (PEG) was used to isolate urinary exosomes. The
efficiency of isolation process was evaluated by the morphology and size
observation, as well as the detection of specific markers (CD63, CD9). The
expression level of exosomal miR-29c, miR-21 and the endogenous control snRNA-U6
were detected by qRT-PCR. The diagnostic potency of urinary exosomal miR-29c and
miR-21 was estimated by the ROC method. Spearman's rank-order correlations
analysis was used to assess the correlation between the miRNAs and clinical
parameters, including pathological index. RESULTS: PEG-based method for isolation
urinary exosome was effective and could be completed with a relatively low-speed
centrifugal machine. Exosomal miR-29c and miR-21 were detected in all samples.
The analysis of miRNAs in urinary exosomes revealed significant dys-regulation of
miR-29c and miR-21 associated with RF. Exosomal miR-29c and miR-21 could predict
degree of RF with AUC of 0.8333 and 0.7639 (P < 0.05). Correlation analysis
showed that the level of miR-29c had a significant negative relationship with
eGFR and the interstitial relative area. CONCLUSIONS: The PEG-based method for
isolation urinary exosome is an inexpensive and easily performed approach. The
application for cargo miRNA analysis is feasible. Urinary exosomal miR-29c may
present a promising diagnostic approach.
PMID- 29330776
TI - Second-Hand Exposure of Staff Administering Vaporised Cannabinoid Products to
Patients in a Hospital Setting.
AB - BACKGROUND: In many health settings, administration of medicinal cannabis poses
significant implementation barriers including drug storage and safety for
administering staff and surrounding patients. Different modes of administration
also provide different yet potentially significant issues. One route that has
become of clinical interest owing to the rapid onset of action and patient
control of the inhaled amount (via breath timing and depth) is that of
vaporisation of cannabinoid products. Although requiring a registered therapeutic
device for administration, this is a relatively safe method of intrapulmonary
administration that may be particularly useful for patients with difficulty
swallowing, and for those in whom higher concentrations of cannabinoids are
needed quickly. A particular concern expressed to researchers undertaking
clinical trials in the hospital is that other patients, nurses, and clinical or
research staff may be exposed to second-hand vapours in the course of
administering vaporised products to patients. OBJECTIVE: The objective of this
study was to take samples from two research staff involved in administering
vaporised Delta9-tetrahydrocannabinol to participants in a clinical trial, to
examine and quantitate cannabinoid presence. METHODS: Blood samples from two
research staff were taken during the exposure period for three participants
(cannabis users) over the course of approximately 2.5 h and analysed using tandem
mass spectrometry. RESULTS: Blood samples taken over a vaporised period revealed
exposure below the limit of detection for Delta9-tetrahydrocannabinol and two
metabolites, using tandem mass spectrometry analytical methods. CONCLUSIONS:
These results are reassuring for hospital and clinical trial practices with staff
administering vaporised cannabinoid products, and helpful to ethics committees
wishing to quantify risk.
PMID- 29330778
TI - Isotopic Exchange HPLC-HRMS/MS Applied to Cyclic Proanthocyanidins in Wine and
Cranberries.
AB - Cyclic B-type proanthocyanidins in red wines and grapes have been discovered
recently. However, proanthocyanidins of a different chemical structure (non
cyclic A-type proanthocyanidins) already known to be present in cranberries and
wine possess an identical theoretical mass. As a matter of fact, the retention
times and the MS/MS fragmentations found for the proposed novel cyclic B-type
tetrameric proanthocyanidin in red wine and the known tetrameric proanthocyanidin
in a cranberry extract are herein shown to be identical. Thus, hydrogen/deuterium
(H/D) exchange was applied to HPLC-HRMS/MS to confirm the actual chemical
structure of the new oligomeric proanthocyanidins. The comparison of the results
in water and deuterium oxide and between wine and cranberry extract indicates
that the cyclic B-type tetrameric proanthocyanidin is the actual constituent of
the recently proposed novel tetrameric species ([C60H49O24]+, m/z 1153.2608).
Surprisingly, the same compound was also identified as the main tetrameric
proanthocyanidin in cranberries. Finally, a totally new cyclic B-type hexameric
proanthocyanidin ([C90H73O36]+, m/z 1729.3876) belonging to this novel class was
identified for the first time in red wine. Graphical Abstract ?.
PMID- 29330779
TI - Correction to: Age at disease onset and peak ammonium level rather than
interventional variables predict the neurological outcome in urea cycle
disorders.
AB - Due to an unfortunate error during the typesetting process, the collaborators
were presented incorrectly.
PMID- 29330780
TI - Safety in Mixed Martial Arts: a 7-Year Review of Cancelled MMA Bouts in Calgary,
Alberta, During the Pre-bout Medical Examination Period.
AB - BACKGROUND: Presently, there is no literature that examines the reasons for the
cancellation of amateur or professional mixed martial arts (MMA) bouts. The
purpose of this study was to review the circumstances that lead to the
cancellation of MMA bouts by Calgary ringside physicians during the pre-bout
examination period and to identify any emerging patterns that may guide the
regulatoin of this sport. METHODS: The case-series was constructed from the
Calgary Combative Sports Commission pre-bout examination records and the medical
records submitted by each athlete from January 2010 to December 2016. RESULTS:
Cancelled bouts in the pre-bout examination periods represented 5.4% of all MMA
bouts in Calgary. A total of 25 reasons lead to bout cancellation and included
the following: failure to obtain required neuroimaging (28.0%), neuroimaging
abnormalities (24.0%), incomplete routine screening investigations (16.0%),
exceeding maximum weight differential between the two athletes (16.0%), injury in
the pre-competition period (8.0%), dehydration (4.0%), and ECG abnormalities
(4.0%). The abnormalities on neuroimaging (n of 6) included the following: post
traumatic gliosis on MRI (n = 1, 16.7%), flares diffusely and findings consistent
with microhemorrhage on MRI (n = 1, 16.7%), chronic orbital fracture with fat pad
extrusion on CT (n = 2, 33.3%), lacunar infarct on MRI (1), and unspecified MRI
abnormality (n = 1, 16.7%). Twenty-two athletes had bouts cancelled and of these
three athletes had their bouts stopped for two reasons. CONCLUSIONS: The
following recommendations are presented and include: the creation of guidelines
regarding pre- and post-bout neuroimaging, the implementation of industry-wide
minimum medical screening standards, the adoption of a longitudinal approach to
weight monitoring, the development of competent ringside physician groups, and
active oversight by the Combative Sports Commission during the matchmaking
process.
PMID- 29330781
TI - A Review of the Methods and Associated Mathematical Models Used in the
Measurement of Fat-Free Mass.
AB - Fat-free mass (FFM) represents the lean component of the body devoid of fat. It
has been shown to be a useful predictor of drug dose requirements, particularly
in obesity where the excess fat mass does not contribute to drug clearance.
However, measuring FFM involves complex and/or expensive experimental
methodologies that preclude their use in routine clinical practice. Thus, models
to predict FFM from readily measurable variables, such as body weight and height,
have been developed and are used in both population pharmacokinetic modelling and
clinical practice. In this review, methods used to measure FFM are explained and
compared in terms of their assumptions, precision, and limitations. These methods
are broadly classified into six different principles: densitometry, hydrometry,
bioimpedance, whole-body counting, dual energy X-ray absorptiometry, and medical
imaging. They vary in their processes and key biological assumptions that are
often not applicable in certain populations (e.g. children, elderly, and certain
disease states). This review provides a summary of the various methods of FFM
measurement and estimation, and links these methods to a scientific framework to
help clinicians and researchers understand the usefulness and potential
limitations of these methods.
PMID- 29330782
TI - Characterization of the Pharmacokinetics of Vilaprisan: Bioavailability,
Excretion, Biotransformation, and Drug-Drug Interaction Potential.
AB - BACKGROUND AND OBJECTIVES: In-vitro data suggest that clearance of vilaprisan is
mediated by cytochrome P450 3A4 (oxidation) and aldoketoreductases (reduction).
To fully understand the elimination and biotransformation pathways of vilaprisan,
a selective progesterone receptor modulator, and to quantify the impact of
cytochrome P450 3A4 inhibition on the pharmacokinetics of vilaprisan, two
clinical studies in healthy postmenopausal women were conducted. METHODS: In
study 1, pharmacokinetics, mass balance, and metabolite patterns were determined
after single oral administration of 5 mg of [14C]-labeled vilaprisan in six
subjects. In study 2, pharmacokinetics were determined after single oral
administration of 4 mg of vilaprisan without and with concomitant administration
of the strong cytochrome P450 3A4 inhibitor itraconazole (200 mg/day) in 14
subjects. In addition, a microtracer dose of vilaprisan was given intravenously
to determine absolute bioavailability, clearance, and volume of distribution.
RESULTS: The dominant single compound in plasma was vilaprisan. No plasma
metabolites exceeding 10% of total drug-related area under the concentration-time
curve were detected. The absolute oral bioavailability of vilaprisan was ~ 60%.
The mean clearance was ~ 7 L/h and the volume of distribution at steady state was
~ 360 L. Excretion occurred primarily via feces (73.5 +/- 3.70% of dose; urine:
13.1 +/- 1.71%; total recovery: 86.6 +/- 2.81%), mostly in a metabolized form.
Only small amounts of the parent drug were found in excreta. When vilaprisan was
administered together with itraconazole, exposure to vilaprisan was increased 6.2
fold (90% confidence interval 5.4-7.2). CONCLUSIONS: Vilaprisan is predominantly
metabolized in the liver to a complex variety of metabolites, which are mainly
excreted with feces. The pivotal role of cytochrome P450 3A4 in the metabolism of
vilaprisan was confirmed. CLINICAL TRIAL REGISTRATION: EudraCT numbers 2013
000707-16 (mass balance study) and 2014-004929-41 (drug-drug
interaction/microtracer study); NCT02456129 (drug-drug interaction/microtracer
study).
PMID- 29330783
TI - Clinical Pharmacokinetics and Pharmacodynamics of Infliximab in the Treatment of
Inflammatory Bowel Disease.
AB - Infliximab was the first monoclonal antibody to be approved for the treatment of
pediatric and adult patients with moderately to severely active Crohn's disease
(CD) and ulcerative colitis (UC). It has been shown to induce and maintain both
clinical remission and mucosal healing in pediatric and adult patients with
inflammatory bowel disease (IBD) who are unresponsive or refractory to
conventional therapies. The administration of infliximab is weight-based and the
drug is administered intravenously. The volume of distribution of infliximab is
low and at steady state ranges from 4.5 to 6 L. Therapeutic monoclonal
antibodies, such as immunoglobulins, are cleared from the circulation primarily
by catabolism. Median infliximab half-life is approximately 14 days. Infliximab
concentration-time data in patients with CD and UC have been shown to be highly
variable within an individual patient over time and between individuals by
multiple population pharmacokinetic models. Covariates that have been identified
to account for a part of the observed inter- and intra-individual variability in
clearance are the presence of antidrug antibodies, use of concomitant
immunomodulators, degree of systemic inflammation, serum albumin concentration,
and body weight, which can affect the pharmacodynamic response. This article
provides a comprehensive review of the clinical pharmacokinetics and
pharmacodynamics of infliximab, as well as the role of therapeutic drug
monitoring in the treatment of IBD.
PMID- 29330784
TI - Tacrolimus Concentration in Saliva of Kidney Transplant Recipients: Factors
Influencing the Relationship with Whole Blood Concentrations.
AB - OBJECTIVE: The objective of this study was to examine the association between
tacrolimus concentration in oral fluids and in whole blood and to investigate the
various factors that influence this relationship. PATIENTS AND METHODS: Forty-six
adult kidney transplant recipients were included in the study. Study A (ten
patients) included the collection of several paired oral fluid samples by passive
drool over a 12-h post-dose period. Study B (36 patients) included the collection
of oral fluids pre-dose and at 2 h after the tacrolimus dose under three
conditions: un-stimulated, after stimulation with a tart candy, and after mouth
rinsing. The tacrolimus concentration in oral fluids was measured by a specially
developed sensitive and specific liquid chromatography mass spectrometry method.
A salivary transferrin concentration of >1 mg/dL was used as a cut-off value for
oral fluid blood contamination. RESULTS: Rinsing the oral cavity before sampling
proved to provide the most suitable sampling strategy giving a correlation
coefficient value of 0.71 (p = 0.001) between the tacrolimus concentration in
oral fluids and the tacrolimus concentration in whole blood at trough. Mean and
95% confidence interval of tacrolimus concentration in oral fluids at the pre
dose concentration for samples collected after mouth rinsing was 584 (436, 782)
pg/mL. The ratio of the tacrolimus concentration in oral fluids to the tacrolimus
concentration in whole blood (*100) was 11% (95% confidence interval 9-13) for
all sampling times. Oral fluid pH or weight of a saliva sample did not influence
the tacrolimus concentration in oral fluids. Tacrolimus distribution into oral
fluids exhibited a delay with a pronounced counter-clockwise hysteresis with
respect to the time after dose. A multivariate analysis of variance revealed that
the tacrolimus concentration in oral fluids is related to the tacrolimus
concentration in whole blood and tacrolimus plasma-binding proteins including
albumin and cholesterol. CONCLUSION: An optimal sampling strategy for the
determination of the tacrolimus concentration in oral fluids was established.
Measuring the tacrolimus concentration in oral fluids appears to be a feasible
and non-invasive method for predicting the concentration of tacrolimus in whole
blood.
PMID- 29330785
TI - Genetic Knockdown and Pharmacologic Inhibition of Hypoxia-Inducible Factor (HIF)
Hydroxylases.
AB - Reduced oxygen supply that does not satisfy tissue and cellular demand (hypoxia)
regularly occurs both in health and disease. Hence, the capacity for cellular
oxygen sensing is of vital importance for each cell to be able to alter its
energy metabolism and promote adaptation to hypoxia. The hypoxia-inducible factor
(HIF) prolyl hydroxylases 1-3 (PHD1-3) and the asparagine hydroxylase factor
inhibiting HIF (FIH) are the primary cellular oxygen sensors, which confer
cellular oxygen-dependent sensitivity upon HIF as well as other hypoxia-sensitive
pathways, such as nuclear factor kappaB (NF-kappaB). Studying these enzymes
allows us to understand the oxygen-dependent regulation of cellular processes and
has led to the development of several putative novel therapeutics, which are
currently in clinical trials for the treatment of anemia associated with kidney
disease. Pharmacologic inhibition and genetic knockdown are commonly established
techniques in protein biochemistry and are used to investigate the activity and
function of proteins. Here, we describe specific protocols for the knockdown and
inhibition of the HIF prolyl hydroxylases 1-3 (PHD1-3) and the asparagine
hydroxylase factor-inhibiting HIF (FIH) using RNA interference (RNAi) and
hydroxylase inhibitors, respectively. These techniques are essential tools for
the analysis of the function of the HIF hydroxylases, allowing the investigation
and discovery of novel functions and substrates of these enzymes.
PMID- 29330786
TI - Kinetic Analysis of HIF Prolyl Hydroxylases.
AB - Kinetic analyses of HIF prolyl 4-hydroxylases (HIF-P4Hs) allow determination of
substrate, cosubstrate and cofactor requirements, analysis of the reaction rate,
and inhibitory properties of the isoenzymes in vitro. Here we describe an assay
measuring the substrate hydroxylation-coupled decarboxylation of radioactive 2
oxoglutarate to radioactive carbon dioxide as a fast, efficient, and diverse
method to analyze the enzyme kinetics of HIF-P4Hs.
PMID- 29330787
TI - Mass Spectrometry and Bioinformatic Analysis of Hydroxylation-Dependent Protein
Protein Interactions.
AB - Characterization of how a stimulus regulates the dynamics of protein-protein
interaction is critical for understanding how a particular protein is regulated
in an intracellular signaling network. Protein hydroxylation, which is a
posttranslational modification catalyzed by oxygen-dependent enzymes, is a
crucial regulator of protein-protein interactions. Under low oxygen conditions,
the activity of many hydroxylases is inhibited, which results in a reduction of
substrate hydroxylation. These changes alter the interactome of the substrate,
and this dynamic rewiring of signaling networks explains crucial aspects of the
adaptive response to hypoxia. In order to fully understand the systemic role of
hydroxylation, it is necessary to identify a comprehensive set of substrates, as
well as to determine which residues are hydroxylated. In addition, hydroxylation
dependent changes in the interactome of the substrates are indicative of the
molecular function of the modification. To identify new substrates of
hydroxylases, we have developed an approach involving the use of a
pharmacological substrate-trap strategy followed by label-free quantitative mass
spectrometry. An overview is provided for the sample preparation, mass
spectrometry techniques, and statistical analysis used for detection of new
substrates, hydroxylated residue, and hydroxylation-dependent protein-protein
interaction changes.
PMID- 29330788
TI - Acquisition of Temporal HIF Transcriptional Activity Using a Secreted Luciferase
Assay.
AB - Here we describe a simple method based on secreted luciferase driven by a hypoxia
inducible factor (HIF) response element (HRE) that allows the acquisition of
dynamic and high-throughput data on HIF transcriptional activity during hypoxia
and pharmacological activation of HIF. The sensitivity of the assay allows for
the secreted luciferase to be consecutively sampled (as little as 1% of the total
supernatant) over an extended time period, thus allowing the acquisition of time
resolved HIF transcriptional activity.
PMID- 29330790
TI - Transcriptional Profiling Using RNA-Seq to Study Hypoxia-Mediated Gene
Regulation.
AB - Exposing cells to a hypoxic environment leads to significant physiological and
molecular alterations. Most of the hypoxic responses are regulated by the
transcription factors known as hypoxia-inducible factors (HIFs). HIF1, a
heterodimer of hypoxia-stabilized subunit HIF-1alpha and a constitutively
expressed subunit HIF-1beta, serves as a key transcription factor that regulates
gene expressions which are involved in cell growth, metabolism, and
proliferation. The global expression patterns can be analyzed by utilizing RNA
Seq to understand the cellular alterations in hypoxia. This technique enables us
to understand the comprehensive regulation of gene expression by specific factors
or environmental stimuli. Here, we describe the complete process of studying
hypoxia-mediated gene expression by using RNA-Seq, including the hypoxic
treatment of cells, RNA isolation, RNA quality check, cDNA library preparation,
and library quality check.
PMID- 29330789
TI - Fluorescence Lifetime Imaging Microscopy (FLIM) as a Tool to Investigate Hypoxia
Induced Protein-Protein Interaction in Living Cells.
AB - Fluorescence resonance energy transfer (FRET) is widely used as a method to
investigate protein-protein interactions in living cells. A FRET pair donor
fluorophore in close proximity to an appropriate acceptor fluorophore transfers
emission energy to the acceptor, resulting in a shorter lifetime of the donor
fluorescence. When the respective FRET donor and acceptor are fused with two
proteins of interest, a reduction in donor lifetime, as detected by fluorescence
lifetime imaging microscopy (FLIM), can be taken as proof of close proximity
between the fluorophores and therefore interaction between the proteins of
interest. Here, we describe the usage of time-domain FLIM-FRET in hypoxia-related
research when we record the interaction of the hypoxia-inducible factor-1 (HIF-1)
subunits HIF-1alpha and HIF-1beta in living cells in a temperature- and CO2
controlled environment under the microscope.
PMID- 29330791
TI - Chromatin Immunoprecipitation of HIF-alpha in Breast Tumor Cells Using Wild Type
and Loss of Function Models.
AB - Chromatin immunoprecipitation (ChIP) is a powerful method to determine whether a
protein of interest binds to specific regulatory elements of the genome. Herein,
we outline protocols optimized to detect binding of Hypoxia-Inducible Factor
(HIF)-1alpha or HIF-2alpha to putative hypoxia response elements (HREs) within
HIF target genes expressed in breast tumor epithelial cells.
PMID- 29330792
TI - Evaluating the Metabolic Impact of Hypoxia on Pancreatic Cancer Cells.
AB - Hypoxia is frequently observed in human cancers and induces global metabolic
reprogramming that includes an increase in glucose uptake and glycolysis,
alterations in NAD(P)H/NAD(P)+ and intracellular ATP levels, and increased
utilization of glutamine as the major precursor for fatty acid synthesis. In this
chapter, we describe in detail various physiological assays that have been
adopted to study the metabolic shift propagated by exposure to hypoxic conditions
in pancreatic cell culture model that includes glucose uptake, glutamine uptake,
and lactate release by pancreatic cancer cell lines. We have also elaborated the
assays to evaluate the ratio of NAD(P)H/NAD(P)+ and intracellular ATP estimation
using the commercially available kit to assess the metabolic state of cancer
cells.
PMID- 29330793
TI - Hypoxia-Induced Metabolomic Alterations in Pancreatic Cancer Cells.
AB - Hypoxic conditions in the pancreatic tumor microenvironment lead to the
stabilization of hypoxia-inducible factor-1 alpha (HIF-1alpha), which acts as the
master regulator of cancer cell metabolism. HIF-1alpha-mediated metabolic
reprogramming results in large-scale metabolite perturbations. Characterization
of the metabolic intermediates and the corresponding metabolic pathways altered
by HIF-1alpha would facilitate the identification of therapeutic targets for
hypoxic microenvironments prevalent in pancreatic ductal adenocarcinoma and other
solid tumors. Targeted metabolomic approaches are versatile in quantifying
multiple metabolite levels in a single platform and, thus, enable the
characterization of multiple metabolite alterations regulated by HIF-1alpha. In
this chapter, we describe a detailed metabolomic approach for characterizing the
hypoxia-induced metabolomic alterations using pancreatic cancer cell lines
cultured in normoxic and hypoxic conditions. We elaborate the methodology of cell
culture, hypoxic exposure, metabolite extraction, and relative quantification of
polar metabolites from normoxia- and hypoxia-exposed cell extracts, using a
liquid chromatography-coupled tandem mass spectrometry approach. Herein, using
our metabolomic data, we also present the methods for metabolomic data
representation.
PMID- 29330794
TI - Hypoxia-Mediated In Vivo Tumor Glucose Uptake Measurement and Analysis.
AB - Most solid tumors are hypoxic in nature due to the limited supply of oxygen to
internal tissues. Hypoxia plays an important role in metabolic adaptations of
tumors that contribute significantly to cancer pathogenesis. Among the several
metabolic alterations induced by hypoxia, hypoxia-mediated increased glucose
uptake serves as the hallmark of metabolic reprogramming. Hypoxia-mediated
stabilization of hypoxia-inducible factor-1 alpha (HIF-1alpha) transcription
factor leads to altered expression of several glycolytic genes and glucose
transporters, which results in increased glucose uptake by tumor cells. Here we
describe an easy and simple way of measuring the hypoxia-mediated tumor glucose
uptake in vivo. The method is based on fluorescent imaging probe, RediJect 2-DG,
which is a nonradioactive fluorescent-tagged glucose molecule. We have discussed
orthotopic tumor implantation of HIF-1alpha knockdown and control pancreatic
cancer cells and glucose uptake measurement in vivo by using IVIS imaging system
along with reagent preparations.
PMID- 29330795
TI - Measurement of Sensory Nerve Activity from the Carotid Body.
AB - Carotid bodies are sensory organs for monitoring chemical composition of the
arterial blood, especially the O2 levels. Carotid bodies are located bilaterally
at the bifurcation of the common carotid artery. Hypoxia increases sensory nerve
activity of the carotid body, which is transmitted to the brainstem neurons
triggering reflex stimulation of breathing and blood pressure. Measurement of
action potentials from the carotid sinus nerve is a widely used approach for
understanding the mechanisms of hypoxic sensing by the carotid body. Here, we
describe the detailed methodology for recording action potential signals from the
carotid sinus nerve from in vivo and ex vivo carotid bodies from rats.
PMID- 29330796
TI - Monitoring Functional Responses to Hypoxia in Single Carotid Body Cells.
AB - The carotid body is the main arterial chemoreceptor in mammals that mediates the
cardiorespiratory reflexes activated by acute hypoxia. Here we describe the
protocols followed in our laboratory to study responsiveness to hypoxia of
single, enzymatically dispersed, glomus cells monitored by microfluorimetry and
the patch-clamp technique.
PMID- 29330797
TI - Testing Acute Oxygen Sensing in Genetically Modified Mice: Plethysmography and
Amperometry.
AB - Monitoring responsiveness to acute hypoxia of whole animals and single cells is
essential to investigate the nature of the mechanisms underlying oxygen (O2)
sensing. Here we describe the protocols followed in our laboratory to evaluate
the ventilatory response to hypoxia in normal and genetically modified animals.
We also describe the amperometric technique used to monitor single-cell
catecholamine release from chemoreceptor cells in carotid body and adrenal
medulla slices.
PMID- 29330798
TI - Immunohistochemistry of the Carotid Body.
AB - Immunohistochemistry (IHC) enables the detection and distribution of proteins in
cells of tissues. IHC has become an indispensable approach for studying oxygen
sensing by the carotid body (CB). This chapter provides a detailed description of
IHC of CB tissue and isolated CB cells.
PMID- 29330799
TI - Hypoxia Signaling and Placental Adaptations.
AB - Oxygen is an essential nutrient for cells. Oxygen is delivered to tissues via red
blood cells through the vasculature. Molecular mechanisms mediating cellular
responses to low oxygen tension have been identified. Hypoxia-inducible factors
(HIFs) are activated by low oxygen and promote transcriptional regulation of
downstream effector genes, which lead to cellular adaptations. Controlled hypoxia
exposure is utilized as an experimental tool to investigate biological processes,
regulating cellular adaptations. Here we describe detailed protocols for hypoxia
exposure of pregnant rodent models and low oxygen exposure of trophoblast stem
cells, utilizing gas-regulated chamber systems. The presentation also includes
phenotypic analyses of the manipulated animal models and cells.
PMID- 29330800
TI - Evaluation of Erythrocyte Changes After Normoxic Return from Hypoxia.
AB - Hypoxia increases erythropoiesis by hypoxia-inducible factors (HIF), principally
by HIF-2, which upregulates erythropoietin transcription. This results in an
increase of red blood cell (RBC) production and delivery of more oxygen to
tissues. Upon rapid return to normoxia, hypoxia-induced polycythemia is
overcorrected by neocytolysis, a transient destruction of preferentially young
RBCs bearing low catalase (downregulated by hypoxia-stimulated microRNA(miR)-21)
caused by reactive oxygen species (ROS) from expanded mitochondria. In order to
study molecular mechanism of neocytolysis, it is critical to differentiate life
span of young and old RBCs and to measure the hematological changes before and
after hypoxia treatment. Here we describe the methodological aspects of these
measurements.
PMID- 29330801
TI - Hypoxic Treatment of Zebrafish Embryos and Larvae.
AB - Zebrafish has emerged as an informative animal model to study the biological
impact and molecular mechanisms of hypoxia. Here we describe a simple method to
induce hypoxia in zebrafish embryos and larvae. This protocol is easy and
reproducible and does not require expensive equipment or specialized devices. It
can be adapted in large, medium, and small scales. This protocol is also well
suited for experiments requiring chemical drug treatment and can be applied to
other fish and amphibian species.
PMID- 29330802
TI - Microinjection of Antisense Morpholinos, CRISPR/Cas9 RNP, and RNA/DNA into
Zebrafish Embryos.
AB - In this chapter, we describe a stepwise protocol of microinjection. Using this
method, antisense morpholinos, CRISPR-Cas9 ribonucleoprotein complexes, capped
mRNA, and DNA can be delivered into fertilized zebrafish eggs to manipulate gene
expression during development. This protocol can also be adapted for
microinjection in other fish and amphibian species.
PMID- 29330803
TI - Western Blot Analysis of C. elegans Proteins.
AB - C. elegans has been widely used as a model organism for basic biological research
and is particularly amenable for molecular genetic studies using a broad
repertoire of techniques. Biochemical approaches, including Western blot
analysis, have emerged as a powerful tool in C. elegans biology for understanding
molecular mechanisms that link genotypes to phenotypes. Here, we provide a
protocol for Western blot analysis using protein extracts obtained from C.
elegans samples.
PMID- 29330804
TI - In Vivo Manipulation of HIF-1alpha Expression During Glioma Genesis.
AB - Hypoxia has long been recognized as a driving force of tumor progression and
therapeutic resistance, and the transcription factor HIF-1alpha is believed to
play a crucial role in these processes. Here we describe an efficient RCAS/Nes
TVA system that allows for in vivo manipulation of HIF-1alpha expression in the
mouse neural progenitor cells. Simple production of the recombinant avian virus
RCAS enables quick delivery of gene of interest through injection into the neural
progenitors of transgenic mice expressing the viral cognate receptor TVA under
the nestin promoter. By crossing with various commercially available genetically
engineered mouse strains, a repertoire of mouse models can be created to study
gene-specific effects on glioma genesis. This chapter provides details of plasmid
construction, viral production, and intracranial delivery of transgenes, a
methodology that can be easily adapted to a specific purpose.
PMID- 29330805
TI - In Vitro Assays of Breast Cancer Stem Cells.
AB - Aldehyde dehydrogenase and mammosphere assays enable the cost-effective
quantification and characterization of cancer stem cells (CSCs) from cancer cell
lines as well as cancer tissue. Here we describe the quantification of CSCs in
breast cancer cell lines using aldehyde dehydrogenase and mammosphere assays
under hypoxic (1% O2) and non-hypoxic (20% O2) culture conditions. Using this
method, a significant enrichment of CSCs compared to bulk populations is observed
when breast cancer cells are exposed to 1% O2 for 72 h.
PMID- 29330806
TI - Fluorescence-Activated Cell Sorting of Murine Mammary Cancer Stem-Like Cell
Subpopulations with HIF Activity.
AB - Fluorescence-activated cell sorting (FACS) is a common method to identify and to
isolate subpopulations within a complex mixture of cells based on their light
scatter and fluorescent staining profiles. FACS is widely used to enrich for
normal tissue and tumor cells that have stem cell potential. Whereas FACS
protocols using conventional breast cancer cell lines are relatively routine,
additional technical challenges are encountered when sorting for cell populations
from freshly digested solid tumors, particularly for use in downstream cancer
stem cell (CSC) assays. First, it is more difficult to isolate live, single cells
from whole tumors, and second, single tumor cells prepared from enzymatically
digested tumors are typically more sensitive to cell death following the physical
stresses of digestion, pipetting, and sorting. Herein methods are described that
have been optimized to harvest and to FACS profile viable tumor epithelial cells
digested from late-stage mammary tumors originating in the mouse mammary tumor
virus (MMTV)-polyomavirus middle T antigen (PyMT) transgenic mouse. Protocols
were designed to enrich for single, viable, MMTV-PyMT tumor cell populations
sorted by FACS and to facilitate the collection of sorted cell subpopulations
suitable for head-to-head comparison of CSC activity by tumorsphere assays in
vitro or limiting dilution transplantation in vivo.
PMID- 29330807
TI - Evaluation of Macrophage Polarization in Pancreatic Cancer Microenvironment Under
Hypoxia.
AB - Hypoxic microenvironment found in pancreatic ductal adenocarcinoma and other
solid tumors is central to physiological and metabolic alterations of immune
cells that significantly impact tumor growth dynamics. Hypoxic adaptations in the
immune cells are primarily mediated by the stabilization of hypoxia-inducible
factor-1 alpha (HIF-1alpha), which regulates cellular metabolism by modulating
glycolysis and other interconnected metabolic pathways. HIF-1alpha plays distinct
roles in M1 and M2 macrophage polarization, which, in turn, regulates tumor cell
immune escape and growth. In this chapter, we describe a real-time PCR-based
assay to monitor the transcript levels of Arg1 and Nos2 to assess the status of
tumor-induced macrophage polarization under hypoxic conditions. This method can
be effectively utilized to delineate the genes critical for M1/M2 polarization in
the hypoxic tumor microenvironment and would provide opportunities to develop
immunomodulating therapies to regulate the tumor growth, progression, and
metastatic dissemination.
PMID- 29330808
TI - Detection of Hypoxia and HIF in Paraffin-Embedded Tumor Tissues.
AB - Hypoxia (insufficient O2 availability) is involved in various biological
processes, such as tumorigenesis and inflammation. Hypoxia results in
stabilization of hypoxia-inducible factors (HIFs) including HIF1alpha and
HIF2alpha. Here we describe a protocol to detect mouse and human tissue hypoxia
by using Hypoxyprobe and immunohistochemical staining for HIF1alpha and
HIF2alpha.
PMID- 29330809
TI - Analysis of Hypoxia and the Hypoxic Response in Tumor Xenografts.
AB - Solid tumors are often characterized by insufficient oxygen supply (hypoxia), as
a result of inadequate vascularization, which cannot keep up with the rapid
growth rate of the tumor. Tumor hypoxia is a negative prognostic and predictive
factor and is associated with a more aggressive phenotype in various tumor
entities. Activation of the hypoxic response in tumors, which is centered around
the hypoxia-inducible transcription factors (HIFs), has been causally linked to
neovascularization, increased radio- and chemoresistance, altered cell
metabolism, genomic instability, increased metastatic potential, and tumor stem
cell characteristics. Thus, the hypoxic tumor microenvironment represents a main
driving force for tumor progression and a potential target for therapeutic
interventions. Here, we describe several methods for the analysis of tumor
hypoxia and the hypoxic response in vivo in tumor xenograft models. These methods
can be applied to various tumor models, including brain tumor xenotransplants,
and allow simultaneously determining the extent and distribution of hypoxia
within the tumor, analyzing HIF levels by immunohistochemistry and immunoblot,
and quantifying the expression of HIF target genes in tumor tissue. The
combination of these approaches provides an important tool to assess the role of
the hypoxic tumor microenvironment in vivo.
PMID- 29330810
TI - Correlation of Glioma Proliferation and Hypoxia by Luciferase, Magnetic
Resonance, and Positron Emission Tomography Imaging.
AB - Gliomas are the most common type of primary, malignant brain tumor and
significantly impact patients, who have a median survival of ~1 year depending on
mutational background. Novel imaging modalities such as luciferase
bioluminescence, micro-magnetic resonance imaging (micro-MRI), micro-computerized
tomography (micro-CT), and micro-positron emission tomography (micro-PET) have
expanded the portfolio of tools available to study this disease. Hypoxia, a key
oncogenic driver of glioma and mechanism of resistance, can be studied in vivo by
the concomitant use of noninvasive MRI and PET imaging. We present a protocol
involving stereotactic injection of syngenic F98 luciferase-expressing glioma
cells generated by our laboratory into Fischer 344 rat brains and imaging using
luciferase. In addition, 18-F-fludeoxyglucose, 18F-fluoromisonidazole, and 18F
fluorothymidine PET imaging are compared with quantified luciferase flux. These
tools can potentially be used for assessing tumor growth characteristics,
hypoxia, mutational effects, and treatment effects.
PMID- 29330811
TI - A nationwide survey of factors influencing adherence to ocular hypotensive
eyedrops in Japan.
AB - INTRODUCTION: Few reports have investigated the status of adherence in Japan on a
large scale. We aimed to investigate the status of adherence to topical glaucoma
treatment and its associated factors. METHODS: A nationwide survey was conducted
as a prospective fashion. Participants in this survey were subjects with primary
open-angle glaucoma, normal-tension glaucoma, or ocular hypertension or
pseudoexfoliation glaucoma who had been prescribed anti-glaucoma ophthalmic
eyedrops and whose ophthalmologist considered prescribing any fixed combination
of ocular hypotensive eyedrops for the first time between 2011 and 2012. Subjects
and their attending ophthalmologists independently completed a questionnaire by
utilizing a fixed combination of ocular hypotensive eyedrops. RESULTS: A total of
1358 ophthalmologists from 1071 medical institutions participated in this survey.
We registered 4430 subjects (2049 males and 2381 females). In total, data from
3853 subjects (87.6%) were analyzed after inclusion of subjects based on
inclusion and exclusion criteria. Good adherence was defined as not forgetting
instillation during the past week. Rates of good adherence reported by subjects
and ophthalmologists were 72.4 and 78.5%, respectively (P < 0.0001). The
consistency of adherence evaluation between subjects and ophthalmologists was
moderate [kappa score 0.5025 (95% confidence interval 0.4740-0.5309)].
Significant factors associated with adherence were size of clinic, age, gender,
number of types of ocular hypotensive eyedrops, ease of instillation, preferred
number of eyedrops, preferred frequency of instillation of eyedrops, and
knowledge of glaucoma. CONCLUSION: Adherence to ocular hypotensive eyedrops among
Japanese subjects was relatively good. Concordance of adherence between subjects'
reports and ophthalmologists' responses was moderate. Size of clinic, number of
types of ocular hypotensive eyedrops, ease of instillation, preferred number of
eyedrops, preferred frequency of instillation of eyedrops, and knowledge of
glaucoma were associated with adherence among Japanese glaucoma subjects.
PMID- 29330813
TI - Characteristics of Elderly Patients Initiating Sitagliptin or Non-DPP-4-Inhibitor
Oral Antihyperglycemic Agents: Analysis of a Cross-Sectional US Claims Database.
AB - INTRODUCTION: Previous analyses concluded that patients initiating treatment with
sitagliptin are older and have more comorbidities than patients initiating
treatment with other oral antihyperglycemic agents (OAHAs). However, these
studies focused on the general population or subjects <= 65 years of age. We
sought to compare differences in baseline characteristics of elderly patients (>=
65 years of age) with T2DM initiating sitagliptin vs. non-DPP-4 inhibitor (non
DPP-4i) OAHA in the MarketScan(r) Medicare Supplemental Database. METHODS:
Relevant patients were identified in the MarketScan(r) Medicare Supplemental
Database and categorized according to the complexity of their antihyperglycemic
treatment: initiating monotherapy, escalating to dual combination therapy, or
escalating to triple combination therapy. Within each category, the comparison
between patients initiating use of sitagliptin or non-DPP-4i OAHA was made within
three age groups: 65-74, 75-84, and >= 85 years. Gender and comorbidity recorded
within the 12 months prior to the index date (date of initiation/escalation of
treatment) were assessed as baseline characteristics in each group. Between
treatment group differences in each covariate were compared using standardized
differences. RESULTS: Patients with T2DM who initiated treatment with sitagliptin
tended to be older and were more likely to have a pre-treatment history of
arrhythmia, congestive heart failure, peripheral vascular disease, renal failure,
and stroke than those initiating non-DPP-4i OAHAs, with the most pronounced
differences observed between patients initiating monotherapy in all three age
groups. As treatment complexity advanced to dual combination therapy, the
differences were attenuated and mostly observed in the 75-84 and >= 85 age
groups. In patients aged 65-74 years initiating triple therapy, no differences
were observed between groups. CONCLUSION: Patients >= 65 years with T2DM
initiating sitagliptin tend to be older and have more comorbidities than those
prescribed other classes of OAHA. Appropriate adjustment is required to minimize
the impact of potential confounding and channeling bias in any comparative
analyses including users of sitagliptin. FUNDING: Merck & Co., Inc., Kenilworth,
NJ, USA.
PMID- 29330812
TI - Evaluation of the Effect of Alogliptin on Tissue Characteristics of the Carotid
Wall: Subanalysis of the SPEAD-A Trial.
AB - INTRODUCTION: Ultrasonic tissue characterization of the carotid wall using gray
scale median (GSM) reflects its composition and low-GSM plaque is considered to
be unstable. The present study evaluated the effect of alogliptin, a dipeptidyl
peptidase-4 inhibitor, on the longitudinal change in GSM, an index of the tissue
characteristics of the carotid wall, in patients with type 2 diabetes (T2DM).
METHODS: This is a post hoc subanalysis using data obtained from the SPEAD-A
trial, a randomized controlled trial that demonstrated the beneficial effect of
alogliptin treatment on the progression of carotid intima-media thickness in
patients with T2DM with no past history of apparent cardiovascular disease. A
total of 322 subjects (161 in the alogliptin treatment group and 161 in the
conventional treatment group) were enrolled. The primary outcome was the change
from baseline in mean GSM-CCA (common carotid artery) during the 104-week
observation period. RESULTS: Both alogliptin treatment and conventional treatment
significantly increased the mean GSM-CCA (from 60.7 +/- 12.3 to 65.9 +/- 10.1, p
< 0.001 and 58.8 +/- 14.4-65.2 +/- 12.2, p < 0.001, respectively) and there was
no significant difference in changes in mean GSM-CCA between the treatment groups
(p = 0.95). Additionally, there were no differences in the changes in the left
and right GSM-CCA between the groups. CONCLUSIONS: A post hoc subanalysis
revealed an improvement of tissue characteristics in the carotid arterial wall in
both the alogliptin treatment group and the conventional treatment group during
the 104-week treatment period and that there was no significant difference
between the treatment groups. CLINICAL TRIAL REGISTRATION: UMIN000019951.
PMID- 29330814
TI - Contrasting effects of alkaline amendments on the bioavailability and uptake of
Cd in rice plants in a Cd-contaminated acid paddy soil.
AB - Reducing cadmium (Cd) concentrations in rice grains is important for food safety,
particularly in acid paddy fields in South China where the soils have been
previously contaminated with Cd. A field experiment was conducted to evaluate the
effects of four alkaline amendments, i.e., lime, compost, biochar, and carbide
slag on soil bioavailability and uptake of Cd in plants of two rice cultivars
(Oryza sativa L.) in a Cd-contaminated acid paddy soil. The addition of these
amendments significantly decreased the concentrations of CaCl2-extractable Cd by
13-41%. Cd in the acid-soluble fraction was decreased in these amended soils
while it increased in the residual fraction. The amendments also decreased the
uptake of Cd in the plants at the tillering and mature growth stages. The
concentrations of Cd in plant tissues at maturity were in the order: root > shoot
> bran > polished rice > husk. The amendment of carbide slag decreased Cd
concentration in rice grains the most, followed by lime, biochar, and compost.
The increases in soil pH and the decreases in the acid-soluble fraction of Cd (F1
Cd) indicated that these amendments can directly transform the highly
availability fraction of Cd to a more stable fraction (residual Cd fraction) in
soils. Furthermore, the Cd concentrations in polished rice grains of the two rice
cultivars used were reduced by 66-67% by treatment with carbide slag. Our study
suggests that carbide slag has a great potential to reduce the bioavailability
and uptake of Cd in rice plants in Cd-contaminated acid paddy field soils.
PMID- 29330815
TI - Supplementing dietary rosemary (Rosmarinus officinalis L.) powder and vitamin E
in broiler chickens: evaluation of humoral immune response, lymphoid organs, and
blood proteins.
AB - The aim of the present study was to evaluate the effect rosemary (Rosmarinus
officinalis L.) powder (RP) and vitamin E (VE) at different levels on humoral
immunity of broilers during a 42-day production cycle. A total of 270 1-day-old
male chicks were assigned to nine groups with three replicates of ten birds each,
and diets were supplemented with 0, 0.5, or 1.0% RP and 0, 100, or 200 mg/kg VE,
respectively. Commercial-inactivated vaccines against avian influenza (AI) and
Newcastle disease (ND) viruses, and living infectious bronchitis virus (IBV)
vaccine were administered by spray method. Sheep red blood cells (SRBC) were
administered subcutaneously. Blood samples were collected from birds 1 week after
each vaccination to determine antibody titers. At the 42nd day, blood samples
were also assessed for globulin level, and lymphoid tissues (thymus, spleen, and
bursa) were weighed. Neither antibody titers against viruses nor lymphoid tissues
weight were affected by RP and/or VE (P > 0.05) treatments. However, broilers
supplemented with 0 mg/kg of VE had lower antibody titers against SRBC than those
fed 100 mg/kg of VE (P < 0.05) at the 24th day. A significant RP * VE interaction
effect (P < 0.05) on plasma globulin level was observed. The findings of our
study suggest that dietary RP and VE additives can interact and modulate the
humoral immunity of broilers, but not sufficiently to improve antibody titers
against specific virus during a 42-day production cycle.
PMID- 29330816
TI - Testing the role of external debt in environmental degradation: empirical
evidence from Turkey.
AB - This study investigates the role of external debt stock in Turkey, which has
suffered from heavy (external and domestic) debt stock for many years. Annual
data from 1960 to 2013 was analyzed using time series analysis in order to study
this. The results confirm the validity of the conventional environmental Kuznets
curve (EKC) in the case of Turkey. However, this study also found that Turkey's
external debt stock did not influence the Turkish economy's long-term EKC
behavior. Fortunately, the results suggest that there are important interactions
among external debt stock, CO2 emissions, energy consumption, and real income;
that is, changes in external debt volume precede changes in these aggregates'
volumes.
PMID- 29330817
TI - Effect of levofloxacin, pazufloxacin, enrofloxacin, and meloxicam on the
immunolocalization of ABCG-2 transporter protein in rabbit retina.
AB - Adenosine triphosphate-binding cassette (ABC) sub-family G member-2 (ABCG-2) is a
transporter protein, implicated for multi-drug efflux from tissues. This study
evaluated the effect of fluoroquinolones; levofloxacin, pazufloxacin and
enrofloxacin, and non-steroidal anti-inflammatory drug, meloxicam; on the
immunolocalization of ABCG-2 transporter protein of rabbit retinas. Thirty-two
male rabbits were randomly divided in to eight groups. Control group was gavaged,
2% benzyl alcohol in 5% dextrose since these chemicals are excipients of the drug
preparations used in the treatment groups of this study. Four groups were
exclusively gavaged, levofloxacin hemihydrate (10 mg/kg body weight b.i.d 12 h),
pazufloxacin mesylate (10 mg/kg body weight b.i.d 12 h), enrofloxacin (20 mg/kg
body weight o.d.), and meloxicam (0.2 mg/kg body weight o.d.), respectively.
Three other groups were co-gavaged meloxicam with above fluoroquinolones,
respectively. These drugs were administered for 21 days. ABCG-2
immunolocalization was mild in the retinas of control and levofloxacin-alone
treated groups. The immunolocalization intensity was significantly higher in
meloxicam-alone-treated group when compared to control and levofloxacin-alone
treated groups. Immunolocalization of this transporter increased in the
levofloxacin-meloxicam co-treated group when compared to the levofloxacin-alone
treated group. Highest immunolocalization was observed in the enrofloxacin
meloxicam co-treated group although the immunolocalization of all treatment
groups, except the levofloxacin-alone-treated group, was significantly higher
than the control and levofloxacin-alone-treated groups.
PMID- 29330818
TI - Trace elements in four freshwater fish from a mine-impacted river: spatial
distribution, species-specific accumulation, and risk assessment.
AB - The concentrations of 16 elements (Mg, Al, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As,
Sr, Cd, Ba, and Pb) were determined in four fish species (Carassius auratus,
Squaliobarbus curriculus, Pelteobagrus fulvidraco, and Silurus asotus) collected
in the Xiang River, a mine-impacted river in Southern China. The mean values of
the elements analyzed in fish muscles were in the decreasing order of Mg > Ca >
Zn > Fe > Sr > Al > Cu > Mn > Ba > As > Cr > Pb > Ni > V > Co > Cd. The
concentrations of Mg, Ca, Sr, Ba, and Cu in omnivorous species were found to be
significantly higher (p < 0.05) than those in carnivorous species. Negative
correlations observed between most element concentrations and fish sizes
indicated the younger individuals accumulated more elements than the older ones.
Principle component analysis and orthogonal partial least squares discriminant
analysis were employed to characterize the effects on element bioaccumulation
using the element concentration matrix. The elemental profiles preferred to
cluster according to differences in fish species rather than in sampling sites.
The potential health risk evaluated through Monte Carlo simulation showed no
appreciable adverse impact on human health from exposure to trace elements in
fish muscles through consumption.
PMID- 29330819
TI - Preparation of a synthetic seed for the common reed harboring an endophytic
bacterium promoting seedling growth under cadmium stress.
AB - Bacterial seed endophytes can facilitate germination and early plant development.
Therefore, the introduction of seed-borne endophytes may improve selected plant
characteristics across generations. In this study, regenerated plantlets of
common reed (Phragmites australis) were inoculated with activated sludge to
obtain a specific functional endophytic bacterium. Denaturing gradient gel
electrophoresis demonstrated that abundant endophytic bacteria could be enriched
in the roots. A siderophore-producing endophytic bacterium was isolated from the
roots and identified as Herbaspirillum frisingense RE3-3 based on 16S rRNA
sequences. This endophyte secrets indole-3-acetic acid to promote plant growth
and cadmium-binding siderophores. The strain was successfully colonized into
synthetic seeds using bacterium-propagule co-cultivation and transmitted to
regenerated seedlings. These seedlings exhibited improved growth under cadmium
stress. This study identifies Herbaspirillum colonization and transmission as a
potentially valuable strategy to improve the phytotoxin resistance of reeds for
constructed wetlands.
PMID- 29330820
TI - Effect of ion exchange on the rate of aerobic microbial oxidation of ammonium in
hyporheic zone sediments.
AB - Microbially mediated ammonium oxidation is a major process affecting nitrogen
transformation and cycling in natural environments. This study investigated
whether ion exchange process can affect microbially mediated aerobic oxidation of
ammonium in a hyporheic zone (HZ) sediments from the Columbia River at US
Department of Energy's Hanford site, Washington State. Experiments were conducted
using synthetic groundwater and river water to investigate their effect on
ammonium oxidation. Results indicated that ammonium sorption through ion exchange
reactions decreased the rate of ammonium oxidation, apparently resulting from the
influence of the ion exchange on dissolved ammonium concentration, thus
decreasing the bioavailability of ammonium for microbial oxidation. However, with
the decrease in dissolved ammonium concentration, the sorbed ammonium released
back to aqueous phase, and became bioavailable so that all the ammonium in the
suspensions were oxidized. Our results implied a dynamic change in ammonium
oxidation rates in an environment such as at HZ where river water and groundwater
with different chemical compositions exchange frequently that can affect ammonium
sorption and desorption through ion exchange reactions.
PMID- 29330821
TI - Effects of ferrous sulfate amendment and water management on rice growth and
metal(loid) accumulation in arsenic and lead co-contaminated soil.
AB - Arsenic (As) and lead (Pb) commonly co-exist with high concentrations in paddy
soil mainly due to human activities in south of China. This study investigates
the effect of ferrous sulfate (FeSO4) amendment and water management on rice
growth and arsenic (As) and lead (Pb) accumulation in rice plants. A paddy soil
co-contaminated with As and Pb was chosen for the pot experiment with three FeSO4
levels (0, 0.25, and 1%, on a dry weight basis) and two water managements
(flooded, non-flooded). The concentrations of As and Pb in iron plaques and rice
plants were determined. Application of FeSO4 and non-flooded conditions
significantly accelerated the growth of rice plants. With the addition of FeSO4,
iron plaques were significantly promoted and most of the As and Pb were
sequestered in the iron plaques. The addition of 0.25% FeSO4 and non-flooded
conditions did not significantly change the accumulation of As and Pb in rice
grains. The practice also significantly decreased the translocation factor (TF)
of As and Pb from roots to above-ground parts which might have been aided by the
reduction of As and Pb availability in soil, the preventing effect of rice roots,
and the formation of more reduced glutathione (GSH). Flooded conditions decreased
the Pb concentration in rice plants, but increased As accumulation. Moreover,
rice grew thin and weak and even died under flooded conditions. Overall, an
appropriate FeSO4 dose and non-flooded conditions might be feasible for rice
cultivation, especially addressing the As issue in the co-contaminated soil.
However, further detailed studies to decrease the accumulation of Pb in edible
parts and the field application in As and Pb co-contaminated soil are
recommended.
PMID- 29330822
TI - Biochemical changes in mussels submitted to different time periods of air
exposure.
AB - Intertidal species face multiple stressors on a daily basis due to their
particular habitat. The submergence at high tide in the aquatic environment and
emergence at low tide to the aerial environment, associated with a wide variation
of abiotic parameters, along with anthropogenic contamination are some of the
daily stresses that these organisms are exposed to. With such a dynamic
environment, organisms developed strategies that allow them to avoid or tolerate
these stressors. Among these species, bivalves are some of the most hypoxia
tolerant, being commonly used as a biomonitoring tool due to their capacity to
accumulate pollutants from the environment and reflect the imposed toxic impacts.
However, when evaluating the response ability of organisms to different stressors
under laboratory conditions, it is not common to consider the fact that exposure
to tides can act as a confounding factor. The present study assessed the effects
of air exposure on the biochemical (metabolic capacity, energy reserves, and
oxidative stress related biomarkers) performance of intertidal Mytilus
galloprovincialis mussels. Specimens of M. galloprovincialis were submitted once
every 24 h to different periods of air exposure (3 and 6 h) for 14 days, under
constant air and seawater temperature (19 +/- 1 degrees C). Results obtained
revealed that air exposure can cause biochemical changes in mussels. The present
findings demonstrated that individuals exposed to air induced superoxide
dismutase (SOD) and catalase (CAT) activity as mechanisms to withstand the
abiotic changes while mobilizing lipid content as the principal source of energy,
and increasing protein content possibly as a result of an increase in the number
of antioxidant defense enzymes. Moreover, individuals under air exposure suffered
higher oxidative damage while showing higher metabolic rate. Results demonstrated
that longer periods of air exposure induced more injuries, since individuals
emerged during 6 h presented higher oxidative stress than individuals under 3 h
of air exposure.
PMID- 29330824
TI - Colonic fistula caused by remaining inflow cannula 14 years after left
ventricular assist device explantation.
AB - Intestinal complication associated with left ventricular assist device (LVAD)
implantation is not rare, and sometimes results in serious condition of patients,
if occurred. We report a rare case in which remaining foreign body after LVAD
explantation resulted in colonic fistula 14 years after LVAD explantation.
PMID- 29330823
TI - Metal Concentrations in Tissues of Gadwall and Common Teal from Miankaleh and
Gomishan International Wetlands, Iran.
AB - Miankaleh and Gomishan International Wetlands are important wintering areas for
waterbirds in the Caspian Sea region. Previous studies revealed increased
exposure to metals in some species of waterbirds using these wetlands. In this
study, we examined concentrations of cadmium (Cd), chromium (Cr), iron (Fe), lead
(Pb), and zinc (Zn) in kidneys, liver, and pectoral muscle of wintering Gadwall
(Anas strepera) and Common Teal (Anas crecca) collected in 2012. In addition, we
measured concentrations of these elements in water and sediments from the
collection sites. The genders differed in only one element/tissue combination,
i.e., concentrations of Fe were greater in the livers of males. Concentrations of
elements observed in Gadwall were generally higher than in Common Teal; only
renal Cr and muscle Zn did not differ between species. Mean Cd concentrations in
Gadwall exceeded background levels, reaching 1.94 MUg/g ww in kidneys and 1.09
MUg/g ww in liver. Similarly, Pb concentrations in Gadwall were also elevated
(4.14 MUg/g ww in kidneys, 3.22 MUg/g ww in liver). Concentrations of other
metals were within ranges commonly found in waterfowl. Concentrations of elements
in the environment were elevated above background and comparable with the data
obtained for this region by other scientists. However, these levels were deemed
to not be great enough to pose an acute health risk to waterfowl. Given increased
concentrations of some metals in duck tissues, further inquiry into the source of
the exposure is needed for this area.
PMID- 29330825
TI - Poststimulation time interval-dependent effects of motor cortex anodal tDCS on
reaction-time task performance.
AB - Anodal transcranial direct current stimulation (tDCS) induces long-term
potentiation-like plasticity, which is associated with long-lasting effects on
different cognitive, emotional, and motor performances. Specifically, tDCS
applied over the motor cortex is considered to improve reaction time in simple
and complex tasks. The timing of tDCS relative to task performance could
determine the efficacy of tDCS to modulate performance. The aim of this study was
to compare the effects of a single session of anodal tDCS (1.5 mA, for 15 min)
applied over the left primary motor cortex (M1) versus sham stimulation on
performance of a go/no-go simple reaction-time task carried out at three
different time points after tDCS-namely, 0, 30, or 60 min after stimulation.
Performance zero min after anodal tDCS was improved during the whole course of
the task. Performance 30 min after anodal tDCS was improved only in the last
block of the reaction-time task. Performance 60 min after anodal tDCS was not
significantly different throughout the entire task. These findings suggest that
the motor cortex excitability changes induced by tDCS can improve motor
responses, and these effects critically depend on the time interval between
stimulation and task performance.
PMID- 29330828
TI - Endorsement of the HerniaSurge guidelines by the Australasian Hernia Society.
PMID- 29330829
TI - Endorsement of the HerniaSurge guidelines by the Americas Hernia Society.
PMID- 29330826
TI - Antibody response to polyomavirus primary infection: high seroprevalence of
Merkel cell polyomavirus and lymphoid tissue involvement.
AB - Human polyomaviruses (HPyVs) asymptomatically infect the human population
establishing latency in the host, and their seroprevalence can reach 90% in
healthy adults. Few studies have focused on the pediatric population, and there
are no reports regarding the seroprevalence of all the newly isolated HPyVs among
Italian children. Therefore, we investigated the frequency of serum antibodies
against 12 PyVs in 182 immunocompetent children from Northeast Italy, by means of
a multiplex antibody detection system. Additionally, secondary lymphoid tissues
were collected to analyze the presence of HPyV DNA sequences using a specific
real-time PCRs or PCRs. Almost 100% of subjects were seropositive for at least
one PyV. Seropositivity ranged from 3% for antibodies against simian virus 40
(SV40) in children from 0 to 3 years, to 91% for antibodies against WU
polyomavirus (WUPyV) and HPyV10 in children from 8 to 17 years. The mean number
of PyV for which children were seropositive increased with the increasing of age:
4 standard deviations (SD) 1.8 in the 0-3-year group, 5 (SD 1.9) in the 4-7-year
group, and 6 (SD 2.2) in the 8-17-year group. JC polyomavirus (JCPyV) DNA was
detected in 1% of the adenoids, WUPyV in 12% of the tonsils, and 28% of the
adenoids, and Merkel cell polyomavirus (MCPyV) was present in 6 and 2% of the
tonsils and adenoids, respectively. Our study gives new insights on the
serological evidence of exposure to PyVs during childhood, and on their possible
respiratory route of transmission.
PMID- 29330830
TI - Endorsement of the HerniaSurge guidelines by the Afro Middle East Hernia Society.
PMID- 29330827
TI - Profiling Online Poker Players: Are Executive Functions Correlated with Poker
Ability and Problem Gambling?
AB - Poker playing and responsible gambling both entail the use of the executive
functions (EF), which are higher-level cognitive abilities. This study
investigated if online poker players of different ability showed different
performances in their EF and if so, which functions were the most discriminating
for their playing ability. Furthermore, it assessed if the EF performance was
correlated to the quality of gambling, according to self-reported questionnaires
(PGSI, SOGS, GRCS). Three poker experts evaluated anonymized poker hand history
files and, then, a trained professional administered an extensive
neuropsychological test battery. Data analysis determined which variables of the
tests correlated with poker ability and gambling quality scores. The highest
correlations between EF test results and poker ability and between EF test
results and gambling quality assessment showed that mostly different clusters of
executive functions characterize the profile of the strong(er) poker player and
those ones of the problem gamblers (PGSI and SOGS) and the one of the cognitions
related to gambling (GRCS). Taking into consideration only the variables
overlapping between PGSI and SOGS, we found some key predictive factors for a
more risky and harmful online poker playing: a lower performance in the emotional
intelligence competences (Emotional Quotient inventory Short) and, in particular,
those grouped in the Intrapersonal scale (emotional self-awareness,
assertiveness, self-regard, independence and self-actualization).
PMID- 29330831
TI - Endorsement of the HerniaSurge guidelines by the International Endohernia
Society.
PMID- 29330832
TI - Endorsement of the HerniaSurge guidelines by the Asia Pacific Hernia Society.
PMID- 29330833
TI - Endorsement of the HerniaSurge guidelines by the European Association of
Endoscopic Surgery.
PMID- 29330834
TI - Endorsement of the Herniasurge guidelines by the European Hernia Society.
PMID- 29330837
TI - Computer simulated modeling of healthy and diseased right ventricular and
pulmonary circulation.
AB - We have previously developed a simulated cardiovascular physiology model for in
silico testing and validation of novel closed-loop controllers. To date, a
detailed model of the right heart and pulmonary circulation was not needed, as
previous controllers were not intended for use in patients with cardiac or
pulmonary pathology. With new development of controllers for vasopressors, and
looking forward, for combined vasopressor-fluid controllers, modeling of right
sided and pulmonary pathology is now relevant to further in-silico validation, so
we aimed to expand our existing simulation platform to include these elements.
Our hypothesis was that the completed platform could be tuned and stabilized such
that the distributions of a randomized sample of simulated patients' baseline
characteristics would be similar to reported population values. Our secondary
outcomes were to further test the system in representing acute right heart
failure and pulmonary artery hypertension. After development and tuning of the
right-sided circulation, the model was validated against clinical data from
multiple previously published articles. The model was considered 'tuned' when
100% of generated randomized patients converged to stability (steady,
physiologically-plausible compartmental volumes, flows, and pressures) and
'valid' when the means for the model data in each health condition were contained
within the standard deviations for the published data for the condition. A fully
described right heart and pulmonary circulation model including non-linear
pressure/volume relationships and pressure dependent flows was created over a 6
month span. The model was successfully tuned such that 100% of simulated patients
converged into a steady state within 30 s. Simulation results in the healthy
state for central venous volume (3350 +/- 132 ml) pulmonary blood volume (405 +/-
39 ml), pulmonary artery pressures (systolic 20.8 +/- 4.1 mmHg and diastolic 9.4
+/- 1.8 mmHg), left atrial pressure (4.6 +/- 0.8 mmHg), PVR (1.0 +/- 0.2 wood
units), and CI (3.8 +/- 0.5 l/min/m2) all met criteria for acceptance of the
model, though the standard deviations of LAP and CI were somewhat narrower than
published comparators. The simulation results for right ventricular infarction
also fell within the published ranges: pulmonary blood volume (727 +/- 102 ml),
pulmonary arterial pressures (30 +/- 4 mmHg systolic, 12 +/- 2 mmHg diastolic),
left atrial pressure (13 +/- 2 mmHg), PVR (1.6 +/- 0.3 wood units), and CI (2.0
+/- 0.4 l/min/m2) all fell within one standard deviation of the reported
population values and vice-versa. In the pulmonary hypertension model, pulmonary
blood volume of 615 +/- 90 ml, pulmonary arterial pressures of 80 +/- 14 mmHg
systolic, 36 +/- 7 mmHg diastolic, and the left atrial pressure of 11 +/- 2 mmHg
all met criteria for acceptance. For CI, the simulated value of 2.8 +/- 0.4
l/min/m2 once again had a narrower spread than most of the published data, but
fell inside of the SD of all published data, and the PVR value of 7.5 +/- 1.6
wood units fell in the middle of the four published studies. The right
ventricular and pulmonary circulation simulation appears to be a reasonable
approximation of the right-sided circulation for healthy physiology as well as
the pathologic conditions tested.
PMID- 29330836
TI - Pathogenesis of non-alcoholic fatty liver disease mediated by YAP.
AB - OBJECTIVE: This study aimed to investigate the mechanism of the interaction
between Yes-associated protein (YAP) and transforming growth factor-beta (TGF
beta)/Smad signaling pathways in the development of non-alcoholic fatty liver
disease (NAFLD). METHODS: Serum samples of monkeys with biopsy-proven NAFLD and
healthy normal monkeys were used to measure fasting plasma glucose (FPG), low
density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG) and
albumin (ALB) with the BECKMAN CX5 PRO. Hematoxylin-eosin staining (H&E) was used
for pathologic analysis, Masson trichrome staining was used to assess for
fibrosis staging, and Oil Red O staining was used to detect lipid droplet
deposition. According to an NAFLD activity score of < 4 points and > 4 points,
the samples were divided into groups: the steatosis group and fibrosing NASH
group. Furthermore, monkeys with a fibrosis stage < 2 were assigned to the mild
fibrosis group, while monkeys with fibrosis stage >= 2 were assigned to the
significant fibrosis group. Moreover, the fibrosis stage was subdivided as
follows: stages 1a, 1c and 2-3. Immunohistochemistry and real-time quantitative
PCR were used to quantify protein and gene expression, respectively. RESULTS: In
the present study, 54 monkeys with NAFLD and 23 normal monkeys were recruited.
Serum FPG and TG levels were higher in fibrosing NASH monkeys compared with
simple steatosis and normal monkeys, and differences between simple steatosis and
normal monkeys were not statistically significant (p > 0.05). YAP increased in
NAFLD, which mainly localized in the nuclei of hepatocytes, perivascular cells
and bile duct cells; the accumulation of YAP correlated with the severity of
hepatocyte injury. Compared with normal monkeys, the expression of TGF-beta,
alpha-smooth muscle actin (alpha-SMA), Drosophila mothers against decapentaplegic
protein 3 (Smad3) and connective tissue growth factor (CTGF) in the liver of
simple steatosis monkeys significantly increased (p < 0.01). Compared with simple
steatosis monkeys, the expression of TGF-beta, alpha-SMA, Smad3 and CTGF in
fibrosing NASH significantly increased (p < 0.01). However, the expression of
Drosophila mothers against decapentaplegic protein 7 (Smad7) in the liver of
fibrosing NASH monkeys significantly decreased (p < 0.01). With the severity of
liver fibrosis, the expression of TGF-beta, alpha-SMA, Smad3 and CTGF gradually
increased, and the difference was statistically significant (p < 0.01). However,
there was no significant difference in the expression of Smad3 between fibrosis
stage 1a and 1c. Compared with normal monkeys, the expression of Smad7 in the
liver of monkeys with fibrosis significantly decreased (p < 0.01), but was
significantly higher at fibrosis stage 1c than at fibrosis stage 1a and 2.
CONCLUSION: The YAP and TGF-beta signaling pathways and the interaction between
them promote the development and progression of NAFLD.
PMID- 29330838
TI - The potential impact of multidimesional geriatric assessment in the social
security system.
AB - AIM: To evaluate the efficacy of multidimensional geriatric assessment (MGA/CGA)
in patients over 65 years old in predicting the release of the accompaniment
allowance (AA) indemnity by a Local Medico-Legal Committee (MLC-NHS) and by the
National Institute of Social Security Committee (MLC-INPS). METHODS: In a
longitudinal observational study, 200 Italian elder citizens requesting AA were
first evaluated by MLC-NHS and later by MLC-INPS. Only MLC-INPS performed a
MGA/CGA (including SPMSQ, Barthel Index, GDS-SF, and CIRS). This report was
written according to the STROBE guidelines. RESULTS: The data analysis was
performed on January 2016. The evaluation by the MLC-NHS and by the MLC-INPS was
in agreement in 66% of cases. In the 28%, the AA benefit was recognized by the
MLC-NHS, but not by the MLC-INPS. By the multivariate analysis, the best
predictors of the AA release, by the MLC-NHS, were represented by gender and the
Barthel Index score. The presence of carcinoma, the Barthel Index score, and the
SPMQ score were the best predictors for the AA release by MLC-INPS. CONCLUSIONS:
MGA/CGA could be useful in saving financial resources reducing the risk of
incorrect indemnity release. It can improve the accuracy of the impairment
assessment in social security system.
PMID- 29330840
TI - Clinical assessment of class II resin-based composites versus preformed metal
crowns performed on primary molars in patients at high risk of caries.
AB - AIM: To compare class II resin composite with preformed metal crowns (PMC) in the
treatment of proximal dentinal caries in high caries-risk patients. METHODS: The
charts (270) of paediatric patients with proximal caries of their primary molars
were reviewed. Success or failure of a procedure was assessed using the dental
notes. Survival analysis was used to calculate the mean survival time (MST) for
both procedures. The influence of variables on the mean survival time was
investigated. RESULTS: A total of 593 class II resin composites and 243 PMCs were
placed in patients ranging between 4-13 years of age. The failure percentage of
class II resin composites was 22.6% with the majority having been due to
recurrent caries, while the failure percentage of PMCs was 15.2% with the
majority due to loss of the crown. There was no significant difference between
the MST of class II resin composites and PMCs, 41.3 and 45.6 months respectively
(p value = 0.06). In class II resin composites, mesial restorations were
associated with lower MST compared to distal restorations (p-value < 0.001).
CONCLUSIONS: The MST of resin composites and PMCs were comparable when performed
on high caries-risk patients.
PMID- 29330841
TI - Delayed replantation of an avulsed immature permanent incisor and apexification
using a novel fast-setting calcium silicate cement containing fluoride: a 3-year
follow-up case report.
AB - BACKGROUND: Traumatic tooth avulsion requires an urgent intervention to replant
the tooth. Prolonged post-injury dry extra-oral conditions worsen the prognosis
and increase the risk of root resorption. Fluoride has the potential to delay
replacement resorption. Calcium silicate cements (CSC) are used to seal the root
canal system and to stimulate periapical regeneration in immature open apex teeth
(apexification). This report suggests the application of a novel fast-setting CSC
with fluoride for apexification in an attempt to hinder root resorption. CASE
REPORT: A delayed replantation of an avulsed open apex permanent central incisor
after 75 h of storage in a dry condition in a 6-year-old girl. Standard treatment
guidelines for avulsed immature permanent teeth were followed. After tooth
replantation a novel fast-setting, CSC containing fluoride was used for
apexification. FOLLOW-UP: The radiographic and clinical evaluations over a period
of 3 years demonstrated periodontal bone healing without root resorption,
mobility, and ankylosis and an acceptable periapical tissue tolerance to the
novel CSC. However, a longer follow-up period is needed. CONCLUSIONS: Delayed
replantation of the avulsed open apex permanent incisor after 75 h of storage
under dry conditions and apexification with a novel fast-setting CSC showed a
successful outcome after 3 years. Novel CSC with fluoride demonstrated an
acceptable biocompatibility and tissue tolerance.
PMID- 29330843
TI - Clinical guideline and recommendations on pre-operative exercise training in
patients awaiting major non-cardiac surgery.
AB - Despite calls for the routine implementation of pre-operative exercise programmes
to optimise patient fitness before elective major surgery, there is no practical
guidance for providing safe and effective exercise in this specific context. The
following clinical guideline was developed following a review of the evidence on
the effects of pre-operative exercise interventions. We developed a series of
best-practice and, where possible, evidence-based statements to advise on patient
care with respect to exercise training in the peri-operative period. These
statements cover: patient selection for exercise training in surgical patients;
integration of exercise training into multi-modal prehabilitation programmes; and
advice on exercise prescription factors and follow-up. Although we acknowledge
that further research is needed to identify the optimal exercise prescription in
different clinical scenarios, we urge peri-operative teams to make use of these
recommendations.
PMID- 29330842
TI - Self-perceived long-term transfer of learning after postpartum hemorrhage
simulation training.
AB - OBJECTIVE: To explore long-term transfer (application of acquired knowledge and
skills on the job) after postpartum hemorrhage simulation training based on
either instructional design (ID) principles or conventional best practice.
METHODS: In this qualitative study, semi-structured interviews with obstetrics
and gynecology healthcare practitioners were conducted between August 7 and
September 26, 2015, in Recife, Brazil. The participants were randomly selected
from each of two postpartum hemorrhage simulations attended 2 years earlier (one
ID and one conventional best practice). Thematic analysis was used to explore (1)
residents' perceptions of long-term transfer of learning, (2) ID elements
influencing the perceived long-term transfer, and (3) differences in the
participants' perceptions according to the type of simulation attended. RESULTS:
There were 12 interview participants. After either simulation format, residents
perceived long-term transfer effects. Training design factors influencing
transfer were, in their opinion, related to trainees' characteristics, simulation
design, and workplace environment. Trainees who participated in the ID-based
simulation perceived better communication skills and better overall situational
awareness: "I didn't do that before." CONCLUSION: All residents perceived long
term transfer after simulation training for postpartum hemorrhage. Those who
attended the ID format additionally perceived improvements in communication
skills and situational awareness, which are fundamental factors in the management
of postpartum hemorrhage.
PMID- 29330839
TI - Peripheral Blood Brain-Derived Neurotrophic Factor as a Biomarker of Alzheimer's
Disease: Are There Methodological Biases?
AB - Mounting evidence that alterations in brain-derived neurotrophic factor (BDNF)
levels and signaling may be involved in the etiopathogenesis of Alzheimer's
disease (AD) has suggested that its blood levels could be used as a biomarker of
the disease. However, higher, lower, or unchanged circulating BDNF levels have
all been described in AD patients compared to healthy controls. Although the
reasons for such different findings are unclear, methodological issues are likely
to be involved. The heterogeneity of participant recruitment criteria and the
lack of control of variables that influence circulating BDNF levels regardless of
dementia (depressive symptoms, medications, lifestyle, lack of overlap between
serum and plasma, and experimental aspects) are likely to bias result and prevent
study comparability. The present work reviews a broad panel of factors, whose
close control could help reduce the inconsistency of study findings, and offers
practical advice on their management. Research directed at elucidating the weight
of each of these variables and at standardizing analytical methodologies is
urgently needed.
PMID- 29330844
TI - Bradykinin mediates the association of collecting duct cells to form migratory
colonies, through B2 receptor activation.
AB - It is known that bradykinin (BK) B2 receptor (B2R) is expressed in the collecting
duct (CD) cells of the newborn rat kidney, but little is known about its role
during early postnatal life. Therefore, we hypothesize that BK could participate
in the mechanisms that mediate CD formation during the postnatal renal
development. Performing primary cultures, combined with biochemical,
immunocytochemical, and time-lapse analysis, we studied the role of BK in CD cell
behavior isolated from renal papilla of neonatal rats. A reverse relationship was
observed between B2R expression and the degree of CD epithelial cell sheet
maturation. BK stimulation induced CD cell association upon B2R activation. The
lack of B2R expression in cells showing mature adherens junctions suggested that
BK is mostly involved in early adhesive events, thus favoring the initial
formation of CD during development. Time-lapse analysis revealed that BK induced
a high protrusive activity of CD cells, denoted by ruffle formation and
lamellipodia extension. PI3K was involved in the BK-induced CD cell-cell
association and the acquisition of the migratory phenotype since, when inhibited,
membrane ruffles, and filopodia between cells diminished. Results indicate that
the actions of BK mediated by PI3K activation were due to the downstream Akt and
Rac pathways. This study, performed with CD cells that were not genetically
manipulated, provides new experimental evidence supporting a novel role of BK in
rat renal CD organization. As B2R blockade results in abnormal tubular
differentiation, our results contribute to better understanding the etiology of
human congenital renal malformation and diseases.
PMID- 29330846
TI - Oral propranolol for infantile haemangioma may be associated with transient gross
motor delay.
PMID- 29330847
TI - Interchangeability of Generic Drugs: A Nonparametric Pharmacokinetic Model of
Gabapentin Generic Drugs.
AB - Substitution by generic drugs is allowed when bioequivalence to the originator
drug has been established. However, it is known that similarity in exposure may
not be achieved at every occasion for all individual patients when switching
between formulations. The ultimate aim of our research is to investigate if
pharmacokinetic subpopulations exist when subjects are exposed to bioequivalent
formulations. For that purpose, we developed a pharmacokinetic model for
gabapentin, based on data from a previously conducted bioavailability study
comparing gabapentin exposure following administration of the gabapentin
originator and three generic gabapentin formulations in healthy subjects. Both
internal and external validation confirmed that the optimal model for description
of the gabapentin pharmacokinetics in this comparative bioavailability study was
a two-compartment model with absorption constant, an absorption lag time, and
clearance adjusted for renal function, in which each model parameter was
separately estimated per administered formulation.
PMID- 29330848
TI - Cultured allogeneic fibroblast injection vs. fibroblasts cultured on amniotic
membrane scaffold for dystrophic epidermolysis bullosa treatment.
AB - BACKGROUND: Different methods of fibroblast application have been examined to
treat recessive dystrophic epidermolysis bullosa (RDEB). OBJECTIVES: To compare
the effects of intradermal injection of cultured allogeneic fibroblasts in
healing RDEB wounds with those of fibroblasts seeded on amniotic membrane
scaffolds (FAMS) or standard wound care (SWC) with Vaseline(r) gauze as controls.
METHODS: Seven patients were recruited, and seven wounds were assessed in each
patient: three wounds were treated with injection of intradermal fibroblasts,
three were treated with FAMS and one was dressed with SWC. Changes in wound size
were assessed after 2 and 12 weeks of treatment. Qualitative wound scores (QWS)
were used to assess wound severity. Additionally, biopsies and antigen mapping
were performed to detect type VII collagen in the dermoepidermal junction.
RESULTS: In both treated areas, the QWS and wound size were significantly
decreased (P < 0.001), whereas there were no changes in the control group (P =
0.29). After 2 and 12 weeks of treatment, the wound size was significantly
decreased in wounds that were treated with fibroblast injection compared with
those treated with FAMS (P < 0.001); but no significant changes were found in the
control group. CONCLUSIONS: Fibroblast injection has been shown to promote
healing of RDEB wounds and is superior to FAMS or the control treatment.
PMID- 29330849
TI - Expression of YAP and TAZ in molluscum contagiosum virus infected skin.
PMID- 29330850
TI - How I Do It: Examining the value of an otology multidisciplinary team meeting.
PMID- 29330845
TI - The association between smoking and cancer incidence in BRCA1 and BRCA2 mutation
carriers.
AB - Tobacco smoke is an established carcinogen, but the association between tobacco
smoking and cancer risk in BRCA mutation carriers is not clear. The aim of this
study was to evaluate prospectively the association between tobacco smoking and
cancer incidence in a cohort of BRCA1 and BRCA2 mutation carriers. The study
population consisted of unaffected BRCA mutation carriers. Information on
lifestyle including smoking histories, reproductive factors, and past medical
histories was obtained through questionnaires. Incident cancers were updated
biennially via follow-up questionnaires. Hazard ratios (HRs) and 95% confidence
intervals (CIs) were estimated using time-dependent Cox regression models. There
were 700 incident cancers diagnosed over 26,711 person-years of follow-up. The
most frequent cancers seen in BRCA mutation carriers were breast (n = 428; 61%)
and ovarian (n = 109; 15%) cancer. Compared to nonsmokers, (ever) smoking was
associated with a modest increased risk of all cancers combined (HR = 1.17; 95%CI
1.01-1.37). Women in the highest group of total pack-years (4.3-9.8) had an
increased risk of developing any cancer (HR = 1.27; 95%CI 1.04-1.56), breast
cancer (HR = 1.33, 95%CI 1.02-1.75), and ovarian cancer (HR = 1.68; 95%CI 1.06
2.67) compared to never smokers. The associations between tobacco smoking and
cancer did not differ by BRCA mutation type or by age at diagnosis. This
prospective study suggests that tobacco smoking is associated with a modest
increase in the risks of breast and ovarian cancer among women with BRCA1 or
BRCA2 mutation.
PMID- 29330851
TI - A case of xeroderma pigmentosum complementation group C with diverse clinical
features.
PMID- 29330852
TI - Characteristics and intestinal immunomodulating activities of water-soluble
pectic polysaccharides from Chenpi with different storage periods.
AB - BACKGROUND: The traditional view considers that Chenpi (dried citrus peel) stored
over the long-term has better health efficacies compared to fresh Chenpi,
although the detailed mechanism responsible for this remains obscure. RESULTS:
The three water-soluble pectic polysaccharides (CPP1, CPP5 and CPP10) were
obtained from 1-, 5- and 10-year Chenpi, respectively, and their physicochemical
characteristics and intestinal immunomodulating activities were investigated and
compared. The results obtained showed that CPP5 and CPP10 demonstrated a lower
dynamic viscosity and degree of methylesterification, as well as a higher
molecular heterogeneity, compared to CPP1. Monosaccharide composition analysis
indicated that CPP1 was composed of arabinose, galacturonic acid and galactose,
and a small amount of rhamnose; however, CPP5 and CPP10 consisted of arabinose,
galacturonic acid, galactose, glucose and xylose, and a small amount of rhamnose.
With the extension of storage period of Chenpi, the content of soluble conjugate
phenolic acids increased in the pectic polysaccharide. Furthermore, it was
confirmed that the pectic polysaccharides extracted from the 5-year and 10-year
Chenpi could significantly enhance the proliferation of bone marrow cells via
activating the Peyer's patch cells in vitro. CONCLUSION: The present study
demonstrates the differences in the pectic polysaccharides from Chenpi with
different storage periods and also confirms that the pectic polysaccharides
extracted from Chenpi stored over the long-term had more significant intestinal
activities compared to that obtained from the fresh Chenpi. This phenomenon might
partly explain why the Chenpi stored over the long-term has better healthcare
effects. (c) 2018 Society of Chemical Industry.
PMID- 29330853
TI - Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) vs.
facemask breathing pre-oxygenation for rapid sequence induction in adults: a
prospective randomised non-blinded clinical trial.
AB - Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) can
prolong apnoea time in adults. Therefore, THRIVE used for pre-oxygenation in
rapid sequence induction of anaesthesia could extend safe apnoea time during
prolonged laryngoscopy and intubation. In this randomised controlled trial, we
compared the lowest peripheral oxygen saturation (SpO2 ) during intubation when
pre-oxygenating with either traditional facemask or THRIVE. Eighty adult
patients, undergoing rapid sequence induction of anaesthesia for emergency
surgery, were randomly allocated to pre-oxygenation with 100% oxygen with
facemask or with THRIVE. Median (IQR [range]) lowest SpO2 until 1 min after
intubation was 99% (97-100 [70-100]%) for the facemask group vs. 99% (99-100 [96
100]%) for the THRIVE group (p = 0.097). Five patients (12.5%) desaturated below
93% when pre-oxygenated with the facemask vs. none in the THRIVE group (p =
0.019). There were no differences in intubation time or apnoea time between the
groups. Median intubation time was 51 (34-66 [22-261]) s in the facemask group
vs. 48 (38-63 [10-146]) s in the THRIVE group (p = 0.99). Median apnoea time was
109 (86-142 [37-291]) s and 116 (92-146 [63-249]) s when using facemask and
THRIVE, respectively (p = 0.49). No signs of regurgitation of gastric content
were detected. The data on desaturation indicate potential benefits of
oxygenation with THRIVE for rapid sequence induction compared with facemask pre
oxygenation.
PMID- 29330854
TI - Combined spinal-epidural vs. spinal anaesthesia for caesarean section: meta
analysis and trial-sequential analysis.
AB - Combined spinal-epidural and single-shot spinal anaesthesia are both used for
caesarean section. It has been claimed in individual trials that combined spinal
epidural is associated with higher sensory spread and greater cardiovascular
stability. We set out to gather all available evidence. We performed: a
systematic literature search to identify randomised controlled trials comparing
combined spinal-epidural with spinal anaesthesia for caesarean section:
conventional meta-analysis; trial-sequential analysis; and assessment of trial
quality using the Grading of Recommendations Assessment, Development, and
Evaluation (GRADE) system. Fifteen trials with high heterogeneity, including 1015
patients, were analysed. There was no significant difference between combined
spinal-epidural and spinal anaesthesia for our primary outcomes maximum sensory
height and vasopressor use (mg ephedrine equivalents). However, trial-sequential
analysis suggested insufficient data and the GRADE scores showed 'very low'
quality of evidence for these outcomes. The secondary outcomes hypotension, time
for sensory block to recede to the level of T10, and the combined outcome of
nausea and vomiting, did not differ significantly between the interventions. The
block times were statistically significantly longer for combined spinal-epidural
in individual trials, but only one trial showed a clinically meaningful
difference (11 min). Based on this analysis, and taking into consideration all
comparisons irrespective of whether drugs had been applied via the epidural
route, there is not enough evidence to postulate any advantage compared with the
spinal technique. Future analyses and studies need to examine the potential
advantages of the combined spinal-epidural technique by using the epidural route
intra- and/or postoperatively.
PMID- 29330855
TI - Getting Innovative Therapies Faster to Patients at the Right Dose: Impact of
Quantitative Pharmacology Towards First Registration and Expanding Therapeutic
Use.
AB - Quantitative pharmacology (QP) applications in translational medicine, drug
development, and therapeutic use were crowd-sourced by the ASCPT Impact and
Influence initiative. Highlighted QP case studies demonstrated faster access to
innovative therapies for patients through 1) rational dose selection for pivotal
trials; 2) reduced trial-burden for vulnerable populations; or 3) simplified
posology. Critical success factors were proactive stakeholder engagement,
alignment on the value of model-informed approaches, and utilizing foundational
clinical pharmacology understanding of the therapy.
PMID- 29330857
TI - Reduction of hyaluronan and increased expression of HYBID (alias CEMIP and
KIAA1199) correlate with clinical symptoms in photoaged skin.
AB - BACKGROUND: Hyaluronan (HA) metabolism in skin fibroblasts is mediated by HYBID
(hyaluronan binding protein involved in hyaluronan depolymerization, alias CEMIP
and KIAA1199) and the HA synthases HAS1 and HAS2. However, photoageing-dependent
changes in HA and their molecular mechanisms, and the relationship between HA
metabolism and clinical symptoms in photoaged skin remain elusive. OBJECTIVES: We
examined the amount, size and tissue distribution of HA and expression levels of
HYBID, HAS1 and HAS2 in photoaged skin, and analysed their relationship with the
degree of photoageing. METHODS: Photoageing-dependent changes of HA were
investigated by studying skin biopsies isolated from photoprotected and
photoexposed areas of the same donors, and the relationships between HA and
photoageing symptoms such as skin wrinkling and sagging were examined. RESULTS:
Skin biopsy specimens showed that the amount and size of HA are decreased in
photoexposed skin compared with photoprotected skin, and this was accompanied by
increased expression of HYBID and decreased expression of HAS1 and HAS2.
Histologically, HA staining in the papillary dermis was decreased in photoexposed
skin, showing reverse correlation with HYBID expression. HYBID expression in the
photoexposed skin directly correlated with skin roughness and sagging parameters,
and the reduced HA staining in the papillary dermis in the photoexposed skin
positively correlated with these symptoms. CONCLUSIONS: These data demonstrate
that imbalance between HYBID-mediated HA degradation and HAS-mediated HA
synthesis may contribute to enhanced HA catabolism in photoaged skin, and suggest
that HYBID-mediated HA reduction in the papillary dermis is related to skin
wrinkling and sagging of photoaged skin.
PMID- 29330856
TI - Reproductive history, breast-feeding and risk of triple negative breast cancer:
The Breast Cancer Etiology in Minorities (BEM) study.
AB - Few risk factors have been identified for triple negative breast cancer (TNBC)
which lacks expression of estrogen receptor (ER), progesterone receptor (PR) and
human epidermal growth factor receptor 2 (HER2). This more aggressive subtype
disproportionately affects some racial/ethnic minorities and is associated with
lower survival. We pooled data from three population-based studies (558 TNBC and
5,111 controls) and examined associations of TNBC risk with reproductive history
and breast-feeding. We estimated odds ratios (ORs) and 95% confidence intervals
(CIs) using multivariable logistic regression. For younger women, aged <50 years,
TNBC risk was increased two-fold for parous women who never breast-fed compared
to nulliparous women (OR = 2.02, 95% CI = 1.12-3.63). For younger parous women,
longer duration of lifetime breast-feeding was associated with a borderline
reduced risk (>=24 vs. 0 months: OR = 0.52, 95% CI = 0.26-1.04, Ptrend = 0.06).
Considering the joint effect of parity and breast-feeding, risk was increased two
fold for women with >=3 full-term pregnancies (FTPs) and no or short-term (<12
months) breast-feeding compared to women with 1-2 FTPs and breast-feeding >=12
months (OR = 2.56, 95% CI = 1.22-5.35). None of these associations were observed
among older women (>=50 years). Differences in reproductive patterns possibly
contribute to the ethnic differences in TNBC incidence. Among controls aged <50
years, the prevalence of no or short-term breast-feeding and >=3 FTPs was highest
for Hispanics (22%), followed by African Americans (18%), Asian Americans (15%)
and non-Hispanic whites (6%). Breast-feeding is a modifiable behavioral factor
that may lower TNBC risk and mitigate the effect of FTPs in women under age 50
years.
PMID- 29330858
TI - Long-term outcomes of cochlear implantation in patients with high-frequency
hearing loss.
AB - OBJECTIVE: To demonstrate the long-term benefits of implantation in patients with
high-frequency sensorineural hearing loss, this report provides 5-year follow-up
on a group of implant recipients who were subjects of the CochlearTM Nucleus(r)
HybridTM L24 Implant System pivotal clinical study. METHODS: The results of three
related clinical studies were compiled to provide outcome data after 1, 3, and 5
years of implant use in a group of subjects who presented with preoperative high
frequency hearing loss and were implanted with a Nucleus Hybrid L24 (Cochlear
Ltd., Sydney, Australia) cochlear implant. A subset of the 50 adult subjects (N =
32) who participated in the Hybrid L24 pivotal Investigational Device Exemption
(IDE) completed comprehensive evaluations at 12 months postactivation, 3 years
postactivation, and then as part of a postapproval study at 5 years
postactivation. Testing included audiometric, speech perception, and subjective
satisfaction measures. RESULTS: Mean unilateral speech perception performance was
significantly improved at all postoperative intervals compared to preoperative
best-aided results and has remained stable to 5 years postactivation. Ninety-four
percent of subjects had measurable hearing, and 72% continued to use electric
acoustic stimulation in the implanted ear after 5 years of implant use.
Subjective satisfaction results support objective performance improvements.
CONCLUSION: Results demonstrate long-term success of patients with high-frequency
hearing loss following Hybrid L24 (Cochlear) cochlear implantation. Benefits
include speech perception abilities significantly better than those in the
preoperative best-aided condition, with additional benefit in those using
electric-acoustic stimulation in the implanted ear. LEVEL OF EVIDENCE: 2b.
Laryngoscope, 1939-1945, 2018.
PMID- 29330859
TI - Differential effects of phototherapy, adalimumab and betamethasone-calcipotriol
on effector and regulatory T cells in psoriasis.
AB - BACKGROUND: Psoriasis is a chronic T-cell-mediated skin disease with marked
social and economic burdens. Current treatments are unsatisfactory, with
unpredictable remission times and incompletely understood modes of action. Recent
advances in our understanding of the pathogenesis of psoriasis have identified
the imbalance between CD4+ T effector cells, particularly the T helper (Th)17
subset, and regulatory T cells (Tregs) as key to the development of psoriatic
lesions, and therefore a novel therapeutic target. OBJECTIVES: To quantify in
patients the effects of three commonly used psoriasis treatment modalities on the
Th1, Th2, Th17 and Treg subsets, and to test whether any change correlates with
clinical response. METHODS: Flow cytometry was used to enumerate Th1, Th2, Th17
and Treg subsets in blood and skin of patients with psoriasis before and after
receiving any of the following treatments: narrowband ultraviolet B (NB-UVB),
adalimumab and topical betamethasone-calcipotriol combination (Dovobet(r) )
RESULTS: All patients responded clinically to the treatments. NB-UVB
significantly increased the numbers of circulating and skin Tregs, while, by
contrast, adalimumab reduced Th17 cells in these compartments, and Dovobet had
dual effects by both increasing Tregs and reducing Th17 cells. CONCLUSIONS: The
differential effects reported here for the above-mentioned treatment modalities
could be exploited to optimize or design therapeutic strategies to overcome the
inflammatory drivers more effectively and restore the Th17-Treg balance in
psoriasis.
PMID- 29330860
TI - Sudden death in sport and riding horses during and immediately after exercise: A
case series.
AB - BACKGROUND: Sudden death affects the health of horses, the safety of riders and
the public perception of animal welfare during equestrian events. OBJECTIVES: To
describe the signalment, clinical history, sudden death episode, rider injuries
and causes of sudden death during exercise or closely thereafter in sport and
pleasure riding horses. STUDY DESIGN: Retrospective case series based on an
online questionnaire. METHODS: An online questionnaire was distributed to the
veterinary and equestrian community. Connections of animals reported in the press
to have died suddenly were sent the survey. Responses were analysed to obtain
information. RESULTS: Fifty-seven cases met inclusion criteria with enough
information to be analysed. The most common discipline was eventing (n = 23,
40.4%), and the most common breed involved was Thoroughbred (n = 23, 40.4%).
Forty-one (71.9%) horses collapsed during exercise, and 16 (28.1%) shortly
thereafter. Twenty-four (42.1%) horses died during or near the time of
competition and 33 (57.9%) during or near the time of training or a pleasure
ride. In 16 (28.1%) horses, the cause of death was known or strongly suspected
based on a post-mortem result, and a cardiovascular origin was reported in 13 of
these 16 cases. Riders were injured in 13 (22.8%) cases, and injuries to their
extremities were the most frequent. MAIN LIMITATIONS: There is potential for
misdiagnosis and recall and selection bias, and in the absence of data on the
total number of horses engaged in equestrian sports and riding, prevalence cannot
be calculated. CONCLUSIONS: Sudden death occurred in many types of equestrian
sports and in riding horses. Death outside competition was more common suggesting
that registries based on reports from official veterinarians underestimate the
magnitude of this problem. Rider injuries were not uncommon when ridden horses
collapsed and died. A definitive diagnosis for the cause of death was not
commonly achieved and cardiovascular origin was the most common where a diagnosis
was proposed by survey respondents.
PMID- 29330861
TI - Validity evidence as a key marker of quality of technical skill assessment in OTL
HNS.
AB - OBJECTIVE: Quality monitoring of assessment practices should be a priority in all
residency programs. Validity evidence is one of the main hallmarks of assessment
quality and should be collected to support the interpretation and use of
assessment data. Our objective was to identify, synthesize, and present the
validity evidence reported supporting different technical skill assessment tools
in otolaryngology-head and neck surgery (OTL-HNS). METHODS: We performed a
secondary analysis of data generated through a systematic review of all published
tools for assessing technical skills in OTL-HNS (n = 16). For each tool, we coded
validity evidence according to the five types of evidence described by the
American Educational Research Association's interpretation of Messick's validity
framework. Descriptive statistical analyses were conducted. RESULTS: All 16 tools
included in our analysis were supported by internal structure and relationship to
variables validity evidence. Eleven articles presented evidence supporting
content. Response process was discussed only in one article, and no study
reported on evidence exploring consequences. CONCLUSION: We present the validity
evidence reported for 16 rater-based tools that could be used for work-based
assessment of OTL-HNS residents in the operating room. The articles included in
our review were consistently deficient in evidence for response process and
consequences. Rater-based assessment tools that support high-stakes decisions
that impact the learner and programs should include several sources of validity
evidence. Thus, use of any assessment should be done with careful consideration
of the context-specific validity evidence supporting score interpretation, and we
encourage deliberate continual assessment quality-monitoring. LEVEL OF EVIDENCE:
NA. Laryngoscope, 128:2296-2300, 2018.
PMID- 29330862
TI - Dermatomyositis: Histopathologic findings of parakeratosis and dermal edema
revisited.
AB - The cutaneous manifestations of dermatomyositis range from classical in the case
of heliotrope rash and Gottron papules to less common papulosquamous and
edematous/vesiculobullous lesions; histopathologic descriptions are dominated by
interface dermatitis. We present a case of dermatomyositis with a combination of
common and rare skin findings, both clinically and histologically. Increased
awareness of papulosquamous and edematous lesions of dermatomyositis can help
direct patient care. Although uncommon, confluent parakeratosis and dermal edema
can be manifestations of dermatomyositis.
PMID- 29330864
TI - Allergy-Committed to progress in allergy and immunology.
PMID- 29330863
TI - Hyoepiglottic ligament collagen and elastin fiber composition and changes
associated with aging.
AB - OBJECTIVE: The epiglottis may contribute to upper airway obstruction in
approximately 10% of patients with obstructive sleep apnea. Clinical experience
indicates that older patients may be more likely to have epiglottis-related
obstruction. This study was designed to examine tissue characteristics of the
hyoepiglottic ligament as a possible factor in epiglottis-related obstruction
based on previous research suggesting that older adults have fewer collagen,
elastin, and muscle fibers in the hyoepiglottic ligament. METHODS: This is a
cross-sectional study of 25 human cadaver hyoepiglottic ligaments. Specimens were
stained using Masson's trichrome and Picrosirius red for collagen fibers and with
Verhoeff-Van Gieson for elastin fibers. Percentage of collagen and elastin fiber
staining for each specimen was calculated and averaged over three regions of each
ligament section. Regression analysis was used to determine the association
between age, smoking history, and collagen and elastin composition of the
hyoepiglottic ligament. RESULTS: The average age of the specimens was 68.4 +/-
15.1 years (range 30-90 years). Increasing age was associated with a lower
percentage of collagen and elastin fibers. When accounting for tobacco use, each
1-year increase in age was associated with a 0.53% decrease in Masson's trichrome
staining (P = 0.004), a 0.35% decrease in Picrosirius red staining (P = 0.023),
and a 0.33% decrease in Verhoeff-Van Gieson staining (P = 0.008). CONCLUSION:
Increasing age is associated with decreases in the collagen and elastin content
of the hyoepiglottic ligament. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:1245
1248, 2018.
PMID- 29330865
TI - A case of radiation-induced osteosarcoma of the skull presenting as a cutaneous
epidermotropic tumor with a short latent period.
AB - Radiation-induced sarcoma (RIS) is an unusual but well documented tumor. The
frequency of RIS of the head and neck region has been reported as 0.143%. In the
literature the median interval between irradiation and development of sarcoma is
11 years. Cases of RIS with a short latent period, that is, less than 4 years are
rare. We report a case of a 34-year-old female who developed an osteosarcoma of
the scalp, over a previous craniotomy scar, 3 years after excision of a frontal
anaplastic oligodendroglioma which had been followed by a course of 6 weeks
radiotherapy (58 Gy) and 6 cycles of temozolomide. The histological features were
those of a high-grade osteosarcoma with epidermotropism of tumor cells. Lymph
nodes were partially replaced by high-grade metastatic osteosarcoma, with extra
nodal lymphatic tumor thrombi. To our knowledge the only other case report of
post-radiation osteosarcoma with a short latency period was a case of
osteosarcoma in the craniofacial bone 3 years after radiotherapy for maxillary
squamous cell carcinoma. The histological finding of prominent replacement of the
epidermis by osteosarcoma has not been reported before.
PMID- 29330866
TI - Enteric viruses' dissemination in a private reserve of natural heritage.
AB - : This study aimed to assess anthropogenic impact of surrounding population in
the Private Reserve of Natural Heritage at Pantanal, the world's largest
freshwater wetland ecosystem located in the centre of South America. Viral
aetiological agents of acute gastroenteritis as rotavirus A (RVA), noroviruses,
human adenoviruses, klassevirus and of hepatitis, as hepatitis A virus, were
investigated in different aquatic matrices. Annual collection campaigns were
carried out from 2009 to 2012, alternating dry and rainy seasons. Viral particles
present in the samples were concentrated by the adsorption-elution method, with
negatively charged membranes, and detected by qualitative and quantitative PCR.
From a total of 43 samples at least one virus was detected in 65% (28) of them.
Viruses were detected in all matrices with concentrations ranging from 2 * 102 to
8.3 * 104 genome copies per litre. A significant higher RVA frequency was
observed in the dry season. Our data revealing dissemination of human enteric
viruses in water matrices both inside and outside the reserve could be useful to
trace faecal contamination in the environment and to minimize the risk of
infection by exposure of susceptible individuals. SIGNIFICANCE AND IMPACT OF THE
STUDY: This study is part of a collaborative project designed to investigate the
environmental and health conditions of the Private Reserve of Natural Heritage at
Pantanal, the largest seasonally flooded wetland in the world. The project aimed
to promote health and quality of human and wildlife extending technical
scientific knowledge about pathogens present in the region. By assessing the
occurrence of human enteric viruses in different water matrices we demonstrated
the anthropogenic impact of surrounding population and pointed out the potential
risk of infection by exposure of susceptible individuals.
PMID- 29330868
TI - Insulin resistance and the increased risk for smell dysfunction in US adults.
AB - OBJECTIVE: Over 24% of older American adults (approximately 14 million) are
estimated to have reduced olfactory sensitivity. Previous studies have provided
evidence that patients with diabetes mellitus (DM) or its complications are at
increased risk of olfactory dysfunction. We therefore investigated whether smell
dysfunction was associated with DM-related biomarkers, including fasting blood
glucose, glycohemoglobin, serum insulin, and homeostasis model assessment of
insulin sensitivity (HOMA-IR), in older US adults. METHODS: Data from 9,678 older
adults who had participated in the 2013 to 2014 National Health and Nutrition
Examination Survey were available for this study. We used the eight-item, self
administered scratch-and-sniff smell test (Sensonics, Inc., Haddon Heights, NJ)
for assessing smell. Smell dysfunction was defined as the condition with an odor
identification score of <= 5. RESULTS: Of the 978 participants, 20% of older
adults (n = 193) were defined as having smell dysfunction. After adjustment for
potential confounding variables, participants in the highest HOMA-IR quintile had
approximately two-fold increased odds (odds ratio = 2.25; 95% confidence
interval: 1.25-4.05) of smell dysfunction compared with those in the lowest HOMA
IR quintile. In contrast, the odds of smell dysfunction were not associated with
the quintiles for fasting blood glucose, glycohemoglobin (HbA1c), or serum
insulin levels. CONCLUSION: We found a significant association between smell
dysfunction and severe insulin resistance in older US adults. Our data suggests
that insulin resistance may be mechanistically linked to loss of smell function.
LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1992-1996, 2018.
PMID- 29330867
TI - Preferential cholinergic excitation of corticopontine neurons.
AB - KEY POINTS: Phasic activation of M1 muscarinic receptors generates transient
inhibition followed by longer lasting excitation in neocortical pyramidal
neurons. Corticopontine neurons in the mouse prefrontal cortex exhibit weaker
cholinergic inhibition, but more robust and longer lasting excitation, than
neighbouring callosal projection neurons. Optogenetic release of endogenous ACh
in response to single flashes of light (5 ms) preferentially enhances the
excitability of corticopontine neurons for many tens of seconds. Cholinergic
excitation of corticopontine neurons involves at least three ionic mechanisms:
suppression of KV 7 currents, activation of the calcium-dependent non-specific
cation conductance underlying afterdepolarizations, and activation of what
appears to be a calcium-sensitive but calcium-permeable non-specific cation
conductance. Preferential cholinergic excitation of prefrontal corticopontine
neurons may facilitate top-down attentional processes and behaviours. ABSTRACT:
Pyramidal neurons in layer 5 of the neocortex comprise two broad classes of
projection neurons: corticofugal neurons, including corticopontine (CPn) neurons,
and intratelencephalic neurons, including commissural/callosal (COM) neurons.
These non-overlapping neuron subpopulations represent discrete cortical output
channels contributing to perception, decision making and behaviour. CPn and COM
neurons have distinct morphological and physiological characteristics, and
divergent responses to modulatory transmitters such as serotonin and
acetylcholine (ACh). To better understand how ACh regulates cortical output, in
slices of mouse prefrontal cortex (PFC) we compared the responsivity of CPn and
COM neurons to transient exposure to exogenous or endogenous ACh. In both neuron
subtypes, exogenous ACh generated qualitatively similar biphasic responses in
which brief hyperpolarization was followed by longer lasting enhancement of
excitability. However, cholinergic inhibition was more pronounced in COM neurons,
while excitatory responses were larger and longer lasting in CPn neurons.
Similarly, optically triggered release of endogenous ACh from cholinergic
terminals preferentially and persistently (for ~40 s) enhanced the excitability
of CPn neurons, but had little impact on COM neurons. Cholinergic excitation of
CPn neurons involved at least three distinct ionic mechanisms: suppression of KV
7 channels (the 'M-current'), activation of the calcium-dependent non-specific
cation conductance underlying afterdepolarizations, and activation of what
appears to be a calcium-sensitive but calcium-permeable non-specific cation
conductance. Our findings demonstrate projection-specific selectivity in
cholinergic signalling in the PFC, and suggest that transient release of ACh
during behaviour will preferentially promote corticofugal output.
PMID- 29330835
TI - International guidelines for groin hernia management.
AB - INTRODUCTION: Worldwide, more than 20 million patients undergo groin hernia
repair annually. The many different approaches, treatment indications and a
significant array of techniques for groin hernia repair warrant guidelines to
standardize care, minimize complications, and improve results. The main goal of
these guidelines is to improve patient outcomes, specifically to decrease
recurrence rates and reduce chronic pain, the most frequent problems following
groin hernia repair. They have been endorsed by all five continental hernia
societies, the International Endo Hernia Society and the European Association for
Endoscopic Surgery. METHODS: An expert group of international surgeons (the
HerniaSurge Group) and one anesthesiologist pain expert was formed. The group
consisted of members from all continents with specific experience in hernia
related research. Care was taken to include surgeons who perform different types
of repair and had preferably performed research on groin hernia surgery. During
the Group's first meeting, evidence-based medicine (EBM) training occurred and
166 key questions (KQ) were formulated. EBM rules were followed in complete
literature searches (including a complete search by The Dutch Cochrane database)
to January 1, 2015 and to July 1, 2015 for level 1 publications. The articles
were scored by teams of two or three according to Oxford, SIGN and Grade
methodologies. During five 2-day meetings, results were discussed with the
working group members leading to 136 statements and 88 recommendations.
Recommendations were graded as "strong" (recommendations) or "weak" (suggestions)
and by consensus in some cases upgraded. In the Results and summary section
below, the term "should" refers to a recommendation. The AGREE II instrument was
used to validate the guidelines. An external review was performed by three
international experts. They recommended the guidelines with high scores. The risk
factors for inguinal hernia (IH) include: family history, previous contra-lateral
hernia, male gender, age, abnormal collagen metabolism, prostatectomy, and low
body mass index. Peri-operative risk factors for recurrence include poor surgical
techniques, low surgical volumes, surgical inexperience and local anesthesia.
These should be considered when treating IH patients. IH diagnosis can be
confirmed by physical examination alone in the vast majority of patients with
appropriate signs and symptoms. Rarely, ultrasound is necessary. Less commonly
still, a dynamic MRI or CT scan or herniography may be needed. The EHS
classification system is suggested to stratify IH patients for tailored
treatment, research and audit. Symptomatic groin hernias should be treated
surgically. Asymptomatic or minimally symptomatic male IH patients may be managed
with "watchful waiting" since their risk of hernia-related emergencies is low.
The majority of these individuals will eventually require surgery; therefore,
surgical risks and the watchful waiting strategy should be discussed with
patients. Surgical treatment should be tailored to the surgeon's expertise,
patient- and hernia-related characteristics and local/national resources.
Furthermore, patient health-related, life style and social factors should all
influence the shared decision-making process leading up to hernia management.
Mesh repair is recommended as first choice, either by an open procedure or a
laparo-endoscopic repair technique. One standard repair technique for all groin
hernias does not exist. It is recommended that surgeons/surgical services provide
both anterior and posterior approach options. Lichtenstein and laparo-endoscopic
repair are best evaluated. Many other techniques need further evaluation.
Provided that resources and expertise are available, laparo-endoscopic techniques
have faster recovery times, lower chronic pain risk and are cost effective. There
is discussion concerning laparo-endoscopic management of potential bilateral
hernias (occult hernia issue). After patient consent, during TAPP, the contra
lateral side should be inspected. This is not suggested during unilateral TEP
repair. After appropriate discussions with patients concerning results tissue
repair (first choice is the Shouldice technique) can be offered. Day surgery is
recommended for the majority of groin hernia repair provided aftercare is
organized. Surgeons should be aware of the intrinsic characteristics of the
meshes they use. Use of so-called low-weight mesh may have slight short-term
benefits like reduced postoperative pain and shorter convalescence, but are not
associated with better longer-term outcomes like recurrence and chronic pain.
Mesh selection on weight alone is not recommended. The incidence of erosion seems
higher with plug versus flat mesh. It is suggested not to use plug repair
techniques. The use of other implants to replace the standard flat mesh in the
Lichtenstein technique is currently not recommended. In almost all cases, mesh
fixation in TEP is unnecessary. In both TEP and TAPP it is recommended to fix
mesh in M3 hernias (large medial) to reduce recurrence risk. Antibiotic
prophylaxis in average-risk patients in low-risk environments is not recommended
in open surgery. In laparo-endoscopic repair it is never recommended. Local
anesthesia in open repair has many advantages, and its use is recommended
provided the surgeon is experienced in this technique. General anesthesia is
suggested over regional in patients aged 65 and older as it might be associated
with fewer complications like myocardial infarction, pneumonia and
thromboembolism. Perioperative field blocks and/or subfascial/subcutaneous
infiltrations are recommended in all cases of open repair. Patients are
recommended to resume normal activities without restrictions as soon as they feel
comfortable. Provided expertise is available, it is suggested that women with
groin hernias undergo laparo-endoscopic repair in order to decrease the risk of
chronic pain and avoid missing a femoral hernia. Watchful waiting is suggested in
pregnant women as groin swelling most often consists of self-limited round
ligament varicosities. Timely mesh repair by a laparo-endoscopic approach is
suggested for femoral hernias provided expertise is available. All complications
of groin hernia management are discussed in an extensive chapter on the topic.
Overall, the incidence of clinically significant chronic pain is in the 10-12%
range, decreasing over time. Debilitating chronic pain affecting normal daily
activities or work ranges from 0.5 to 6%. Chronic postoperative inguinal pain
(CPIP) is defined as bothersome moderate pain impacting daily activities lasting
at least 3 months postoperatively and decreasing over time. CPIP risk factors
include: young age, female gender, high preoperative pain, early high
postoperative pain, recurrent hernia and open repair. For CPIP the focus should
be on nerve recognition in open surgery and, in selected cases, prophylactic
pragmatic nerve resection (planned resection is not suggested). It is suggested
that CPIP management be performed by multi-disciplinary teams. It is also
suggested that CPIP be managed by a combination of pharmacological and
interventional measures and, if this is unsuccessful, followed by, in selected
cases (triple) neurectomy and (in selected cases) mesh removal. For recurrent
hernia after anterior repair, posterior repair is recommended. If recurrence
occurs after a posterior repair, an anterior repair is recommended. After a
failed anterior and posterior approach, management by a specialist hernia surgeon
is recommended. Risk factors for hernia incarceration/strangulation include:
female gender, femoral hernia and a history of hospitalization related to groin
hernia. It is suggested that treatment of emergencies be tailored according to
patient- and hernia-related factors, local expertise and resources. Learning
curves vary between different techniques. Probably about 100 supervised laparo
endoscopic repairs are needed to achieve the same results as open mesh surgery
like Lichtenstein. It is suggested that case load per surgeon is more important
than center volume. It is recommended that minimum requirements be developed to
certify individuals as expert hernia surgeon. The same is true for the
designation "Hernia Center". From a cost-effectiveness perspective, day-case
laparoscopic IH repair with minimal use of disposables is recommended. The
development and implementation of national groin hernia registries in every
country (or region, in the case of small country populations) is suggested. They
should include patient follow-up data and account for local healthcare
structures. A dissemination and implementation plan of the guidelines will be
developed by global (HerniaSurge), regional (international societies) and local
(national chapters) initiatives through internet websites, social media and
smartphone apps. An overarching plan to improve access to safe IH surgery in low
resource settings (LRSs) is needed. It is suggested that this plan contains
simple guidelines and a sustainability strategy, independent of international
aid. It is suggested that in LRSs the focus be on performing high-volume
Lichtenstein repair under local anesthesia using low-cost mesh. Three chapters
discuss future research, guidelines for general practitioners and guidelines for
patients. CONCLUSIONS: The HerniaSurge Group has developed these extensive and
inclusive guidelines for the management of adult groin hernia patients. It is
hoped that they will lead to better outcomes for groin hernia patients wherever
they live. More knowledge, better training, national audit and specialization in
groin hernia management will standardize care for these patients, lead to more
effective and efficient healthcare and provide direction for future research.
PMID- 29330869
TI - Three-year analysis of zirconia implants used for single-tooth replacement and
three-unit fixed dental prostheses: A prospective multicenter study.
AB - AIM: The aim of the present investigation was to evaluate clinically and
radiographically the outcome of zirconia oral implants after 3 years in function.
MATERIALS AND METHODS: In 60 patients in need of either a single-tooth
replacement or a three-unit fixed dental prosthesis (FDP), a total of 71 one
piece zirconia implants were placed and immediately restored with temporary fixed
prostheses. After a period of at least 2 months in the mandible and at least 4
months in the maxilla, zirconia-based reconstructions were cemented. The implants
were clinically and radiologically examined at implant insertion, prosthetic
delivery, at 6 months and then yearly up to 3 years. A linear mixed model was
used to analyze statistically the influence of prognostic factors on changes in
the marginal bone level. RESULTS: Seventy-one implants (48 in the mandible, 23 in
the maxilla) inserted in 60 patients were restored with 49 crowns and 11 FDP. One
patient lost his implant after 5 weeks. Five patients with one implant each could
not be evaluated after 3 years. Based on 55 patients with a total of 66 implants,
the mean survival rate was 98.5% after 3 years in function. A statistically
significant mean marginal bone loss (0.70 mm +/- 0.72 mm) has been detected from
implant insertion to the 3-year follow-up. The largest marginal bone loss
occurred between implantation and prosthetic delivery (0.67 mm +/- 0.56 mm).
After delivery, no statistically significant bone level change was observed (0.02
mm +/- 0.59 mm). None of the investigated prognostic factors had a significant
influence on changes in the marginal bone level. CONCLUSIONS: After 3 years in
function, the investigated one-piece zirconia implant showed a high survival rate
and a low marginal bone loss. The implant system was successful for single-tooth
replacement and three-unit FDPs. Further investigations with long-term data are
needed to confirm these findings.
PMID- 29330870
TI - Cell therapy for spinal cord injury with olfactory ensheathing glia cells (OECs).
AB - The prospects of achieving regeneration in the central nervous system (CNS) have
changed, as most recent findings indicate that several species, including humans,
can produce neurons in adulthood. Studies targeting this property may be
considered as potential therapeutic strategies to respond to injury or the
effects of demyelinating diseases in the CNS. While CNS trauma may interrupt the
axonal tracts that connect neurons with their targets, some neurons remain alive,
as seen in optic nerve and spinal cord (SC) injuries (SCIs). The devastating
consequences of SCIs are due to the immediate and significant disruption of the
ascending and descending spinal pathways, which result in varying degrees of
motor and sensory impairment. Recent therapeutic studies for SCI have focused on
cell transplantation in animal models, using cells capable of inducing axon
regeneration like Schwann cells (SchCs), astrocytes, genetically modified
fibroblasts and olfactory ensheathing glia cells (OECs). Nevertheless, and
despite the improvements in such cell-based therapeutic strategies, there is
still little information regarding the mechanisms underlying the success of
transplantation and regarding any secondary effects. Therefore, further studies
are needed to clarify these issues. In this review, we highlight the properties
of OECs that make them suitable to achieve neuroplasticity/neuroregeneration in
SCI. OECs can interact with the glial scar, stimulate angiogenesis, axon
outgrowth and remyelination, improving functional outcomes following lesion.
Furthermore, we present evidence of the utility of cell therapy with OECs to
treat SCI, both from animal models and clinical studies performed on SCI
patients, providing promising results for future treatments.
PMID- 29330872
TI - Repair of high-grade posterior glottic stenosis: A novel criocarytenoid joint
release technique.
PMID- 29330871
TI - Multi-site N-Glycan mapping study 2: UHPLC.
AB - In the first part of this publication, the results from an international study
evaluating the precision (i.e., repeatability and reproducibility) of N
glycosylation analysis using capillary electrophoresis of APTS-labeled N-glycans
were presented. The corresponding results from ultra-high performance liquid
chromatography (UHPLC) with fluorescence detection are presented here from 12
participating sites. All participants used the same lot of samples, reagents, and
columns to perform the assays. Elution time, peak area and peak area percent
values were determined for all peaks >=0.1% peak area, and statistical analysis
was performed following ISO 5725-2 guideline principles. The results demonstrated
adequate reproducibility, within any given site as well across all sites,
indicating that standard UHPLC-based N-glycan analysis platforms are appropriate
for general use.
PMID- 29330874
TI - Safety of high-current stimulation for intermittent intraoperative neural
monitoring in thyroid surgery: A porcine model.
AB - OBJECTIVES: During monitored thyroidectomy, displacement of the recurrent
laryngeal nerve (RLN) or vagus nerve (VN) in some complicated cases can increase
the risk of injury. Although increasing the stimulus current can facilitate nerve
mapping and localization, the safety of a high-current stimulus remains unknown.
Therefore, this study evaluated the safety of a high-current stimulus in a
porcine model. METHODS: Short-duration (1 minute), high-current (3, 5, 10, 15,
20, 25, and 30 mA at 4Hz) stimulus pulses were repeatedly applied to the RLN or
VN in six anesthetized piglets. The safety of the high-current stimulus pulses
was assessed in terms of hemodynamic stability during VN stimulation and in terms
of nerve function integrity after VN and RLN stimulation. RESULTS: During VN
stimulation with a high-current stimulus pulse, sinus rhythms in all six piglets
showed stable heart rates, and mean arterial pressure was unaffected. High
current stimulation of the VN and the RLN did not affect electromyography
amplitude or latency. CONCLUSION: This porcine study showed that applying a short
duration, high-current stimulus pulse to the VN or RLN during monitored
thyroidectomy has no harmful effects. In clinical practice, a short duration of
high-current stimulus can be applied to facilitate neural mapping, especially in
patients with disoriented nerve positions. LEVEL OF EVIDENCE: NA. Laryngoscope,
128:2206-2212, 2018.
PMID- 29330875
TI - Performance of the Early Access AmpliSeqTM Mitochondrial Panel with degraded DNA
samples using the Ion TorrentTM platform.
AB - The Early Access AmpliSeqTM Mitochondrial Panel amplifies whole mitochondrial
genomes for phylogenetic and kinship identifications, using Ion TorrentTM
technology. There is currently limited information on its performance with
degraded DNA, a common occurrence in forensic samples. This study evaluated the
performance of the Panel with DNA samples degraded in vitro, to mimic conditions
commonly found in forensic investigations. Purified DNA from five individuals was
heat-treated at five time points each (125 degrees C for 0, 30, 60, 120, and 240
min; total n = 25). The quality of DNA was assessed via a real-time DNA assay of
genomic DNA and prepared for massively parallel sequencing on the Ion TorrentTM
platform. Mitochondrial sequences were obtained for all samples and had an
amplicon coverage averaging between 66X to 2803X. Most amplicons (157/162)
displayed high coverages (452 +/- 333X), while reads with less than 100X coverage
were recorded in five amplicons only (90 +/- 5X). Amplicon coverage was decreased
with prolonged heating. At 72% strand balance, reads were well balanced between
forward and reverse strands. Using a coverage threshold of ten reads per SNP,
complete sequences were recovered in all samples and resolved kinship and,
haplogroup relations. Additionally, the HV1 and HV2 regions of the reference and
240-min heat-treated samples (n = 10) were Sanger-sequenced for concordance.
Overall, this study demonstrates the efficacy of a novel forensic Panel that
recovers high quality mitochondrial sequences from degraded DNA samples.
PMID- 29330873
TI - Coupling colloidal forces with yield stress of charged inorganic particle
suspension: A review.
AB - This paper aims to summarize the series of investigations on coupling suspension
yield stress and DLVO (Derjaguin-Landau-Verwey-Overbeek) forces, i.e. van der
Waals and electrical double layer forces. This summary provides a better
understanding of the basic phenomena associated, historical development and
current status of this useful coupling, and also discusses the applicability and
limitations/variations of such coupling applied to different types of
concentrated aqueous particle suspensions. Aqueous suspensions discussed are
composed of charged inorganic fine particles, including metal oxide colloidal
particles, mineral fine particles, and clays. The research gaps are identified
and specific future perspectives are discussed to further enhance the use of this
unique and useful coupling, and to aim for the transition from the modelling of
similar particle suspension systems to its dissimilar/mix particle suspension
systems that fit more with the current and future industry needs in particle
processing.
PMID- 29330876
TI - A rare case of topical methazolamide ophthalmic solution causing death due to
toxic epidermal necrolysis.
PMID- 29330877
TI - Characterization of biologic response modifiers in the supernatant of
conventional, refrigerated, and cryopreserved platelets.
AB - BACKGROUND: Alternatives to room temperature storage of platelets (PLTs) are of
interest to support blood banking logistics. The aim of this study was to compare
the presence of biologic response modifiers (BRMs) in PLT concentrates stored
under conventional room temperature conditions with refrigerated or cryopreserved
PLTs. STUDY DESIGN AND METHODS: A three-arm pool-and-split study was carried out
using buffy coat-derived PLTs stored in 30% plasma/70% SSP+. The three matched
treatment arms were as follows: room temperature (20-24 degrees C), cold (2-6
degrees C), and cryopreserved (-80 degrees C with DMSO). Liquid-stored PLTs were
tested over a 21-day period, while cryopreserved PLTs were tested immediately
after thawing and reconstitution in 30% plasma/70% SSP+ and after storage at room
temperature. RESULTS: Coagulation factor activity was comparable between room
temperature and cold PLTs, with the exception of protein S, while cryopreserved
PLTs had reduced Factor (F)V and FVIII activity. Cold-stored PLTs retained alpha
granule proteins better than room temperature or cryopreserved PLTs.
Cryopreservation resulted in 10-fold higher microparticle generation than cold
stored PLTs, but both groups contained significantly more microparticles than
those stored at room temperature. The supernatant from both cold and
cryopreserved PLTs initiated faster clot formation and thrombin generation than
room temperature PLTs. CONCLUSION: Cold storage and cryopreservation alter the
composition of the soluble fraction of stored PLTs. These differences in
coagulation proteins, cytokines, and microparticles likely influence both the
hemostatic capacity of the components and the auxiliary functions.
PMID- 29330878
TI - Identification of tentative marker in Corvina and Primitivo wines with CMC-se.
AB - This paper introduces CMC-se-a program for computer-assisted structure
elucidation. In the experimental part, the combination of modern analytical
methods (LC-SPE-NMR/MS) and structure elucidation software is used for the
identification of tentative markers in red wines.
PMID- 29330879
TI - Biotechnological conversion of spent coffee grounds into lactic acid.
AB - : This work investigates the potential bioconversion of spent coffee grounds
(SCG) into lactic acid (LA). SCG were hydrolysed by a combination of dilute acid
treatment and subsequent application of cellulase. The SCG hydrolysate contained
a considerable amount of reducing sugars (9.02 +/- 0.03 g l-1 , glucose; 26.49 +/
0.10 g l-1 galactose and 2.81 +/- 0.07 g l-1 arabinose) and it was used as a
substrate for culturing several lactic acid bacteria (LAB) and LA-producing
Bacillus coagulans. Among the screened micro-organisms, Lactobacillus rhamnosus
CCM 1825 was identified as the most promising producer of LA on a SCG
hydrolysate. Despite the inhibitory effect exerted by furfural and phenolic
compounds in the medium, reasonably high LA concentrations (25.69 +/- 1.45 g l-1
) and yields (98%) were gained. Therefore, it could be demonstrated that SCG is a
promising raw material for the production of LA and could serve as a feedstock
for the sustainable large-scale production of LA. SIGNIFICANCE AND IMPACT OF THE
STUDY: Spent coffee grounds (SCG) represent solid waste generated in millions of
tonnes by coffee-processing industries. Their disposal represents a serious
environmental problem; however, SCG could be valorized within a biorefinery
concept yielding various valuable products. Herein, we suggest that SCG can be
used as a complex carbon source for the lactic acid production.
PMID- 29330880
TI - Concise Review: Optimized Strategies for Stem Cell-Based Therapy in Myocardial
Repair: Clinical Translatability and Potential Limitation.
AB - Ischemic heart diseases (IHDs) remain major public health problems with high
rates of morbidity and mortality worldwide. Despite significant advances, current
therapeutic approaches are unable to rescue the extensive and irreversible loss
of cardiomyocytes caused by severe ischemia. Over the past 16 years, stem cell
based therapy has been recognized as an innovative strategy for cardiac
repair/regeneration and functional recovery after IHDs. Although substantial
preclinical animal studies using a variety of stem/progenitor cells have shown
promising results, there is a tremendous degree of skepticism in the clinical
community as many stem cell trials do not confer any beneficial effects. How to
accelerate stem cell-based therapy toward successful clinical application
attracts considerate attention. However, many important issues need to be fully
addressed. In this Review, we have described and compared the effects of
different types of stem cells with their dose, delivery routes, and timing that
have been routinely tested in recent preclinical and clinical findings. We have
also discussed the potential mechanisms of action of stem cells, and explored the
role and underlying regulatory components of stem cell-derived
secretomes/exosomes in myocardial repair. Furthermore, we have critically
reviewed the different strategies for optimizing both donor stem cells and the
target cardiac microenvironments to enhance the engraftment and efficacy of stem
cells, highlighting their clinical translatability and potential limitation. Stem
Cells 2018;36:482-500.
PMID- 29330882
TI - Rate of Cough During Treatment With Angiotensin-Converting Enzyme Inhibitors: A
Meta-Analysis of Randomized Placebo-Controlled Trials.
AB - Use of protective angiotensin-converting enzyme inhibitors (ACE-I) in patients
with cardiovascular disease (CVD) is sometimes limited by incident coughing. In
clinical trials, cough occurred also on placebo. We performed a meta-analysis
including randomized, placebo-controlled trials reporting cough on ACE-I in
patients with CVD. We evaluated the attributable fraction of cough on ACE-I
accounting rate on placebo: placebo-adjusted ACE-I (%) = (ACE-I (%) - Placebo
(%)) / ACE-I (%). In total, 65,054 patients from 22 included studies were
analyzed. Placebo-adjusted ACE-I cough was 37% of 13.5% reported cases on ACE-I,
while 8.5% reported cases on placebo were equivalent to 63% of cases on ACE-I,
indicating potential other factors for cough than ACE-I in a substantial number
of cough cases on ACE-I. Placebo-adjusted ACE-I cough had the highest rates of
arterial hypertension (85%) and the lowest of heart failure (29%). Therefore,
other causes of cough, particularly in heart failure, should be excluded before
ACE-I withdrawal.
PMID- 29330881
TI - Cocaine and HIV-1 Tat disrupt cholesterol homeostasis in astrocytes: Implications
for HIV-associated neurocognitive disorders in cocaine user patients.
AB - Cholesterol synthesis and clearance by astrocytes are tightly regulated to
maintain constant levels within the brain. In this context, liver X receptors
(LXRs) are the master regulators of cholesterol homeostasis in the central
nervous system (CNS). Increasing levels of cholesterol in astrocytes trigger LXR
activation leading to the transcription of target genes involved in cholesterol
trafficking and efflux, including apolipoprotein E, cytochrome P450 enzymes,
sterol regulatory binding protein, and several ATP-binding cassette transporter
proteins. The disturbance of LXR signaling in the brain can lead to significant
dysfunctions in cholesterol homeostasis, and disruptions in this pathway have
been implicated in numerous neurological diseases including Alzheimer's disease
and Huntington's disease. HIV infection of the CNS in combination with cocaine
use is associated with astrocyte and neuronal energy deficit and damage. We
propose that dysregulation in CNS cholesterol metabolism may be involved in the
progression of HIV-associated neurocognitive disorders (HAND) and in cocaine
mediated neurocognitive impairments. We hypothesize that exposure of astrocytes
to cocaine and the HIV protein Tat will disrupt LXR signaling. Alterations in
these pathways will in turn, affect cholesterol bioavailability for neurons. Our
data show that exposure of astrocytes to cocaine and HIV-Tat significantly
decreases LXRbeta levels, downstream signaling and bioavailability of
cholesterol. Taken together, these data uncover novel alterations in a
bioenergetic pathway in astrocytes exposed to cocaine and the HIV protein Tat.
Results from these studies point to a new pathway in the CNS that may contribute
to HAND in HIV+ cocaine user individuals.
PMID- 29330884
TI - Synapsin III is a key component of alpha-synuclein fibrils in Lewy bodies of PD
brains.
AB - Lewy bodies (LB) and Lewy neurites (LN), which are primarily composed of alpha
synuclein (alpha-syn), are neuropathological hallmarks of Parkinson's disease
(PD) and dementia with Lewy bodies (DLB). We recently found that the neuronal
phosphoprotein synapsin III (syn III) controls dopamine release via cooperation
with alpha-syn and modulates alpha-syn aggregation. Here, we observed that LB and
LN, in the substantia nigra of PD patients and hippocampus of one subject with
DLB, displayed a marked immunopositivity for syn III. The in situ proximity
ligation assay revealed the accumulation of numerous proteinase K-resistant
neuropathological inclusions that contained both alpha-syn and syn III in tight
association in the brain of affected subjects. Most strikingly, syn III was
identified as a component of alpha-syn-positive fibrils in LB-enriched protein
extracts from PD brains. Finally, a positive correlation between syn III and
alpha-syn levels was detected in the caudate putamen of PD subjects.
Collectively, these findings indicate that syn III is a crucial alpha-syn
interactant and a key component of LB fibrils in the brain of patients affected
by PD.
PMID- 29330883
TI - Genotype-phenotype correlations in individuals with pathogenic RERE variants.
AB - Heterozygous variants in the arginine-glutamic acid dipeptide repeats gene (RERE)
have been shown to cause neurodevelopmental disorder with or without anomalies of
the brain, eye, or heart (NEDBEH). Here, we report nine individuals with NEDBEH
who carry partial deletions or deleterious sequence variants in RERE. These
variants were found to be de novo in all cases in which parental samples were
available. An analysis of data from individuals with NEDBEH suggests that point
mutations affecting the Atrophin-1 domain of RERE are associated with an
increased risk of structural eye defects, congenital heart defects, renal
anomalies, and sensorineural hearing loss when compared with loss-of-function
variants that are likely to lead to haploinsufficiency. A high percentage of RERE
pathogenic variants affect a histidine-rich region in the Atrophin-1 domain. We
have also identified a recurrent two-amino-acid duplication in this region that
is associated with the development of a CHARGE syndrome-like phenotype. We
conclude that mutations affecting RERE result in a spectrum of clinical
phenotypes. Genotype-phenotype correlations exist and can be used to guide
medical decision making. Consideration should also be given to screening for RERE
variants in individuals who fulfill diagnostic criteria for CHARGE syndrome but
do not carry pathogenic variants in CHD7.
PMID- 29330885
TI - Prolonged duration of persistent cell-free fetal DNA from vanishing twin.
PMID- 29330886
TI - Surgery and magnetic resonance imaging increase the risk of hypothermia in
infants.
AB - AIM: Maintaining normothermia is a tenet of neonatal care. However, neonatal
thermal care guidelines applicable to intra-hospital transport beyond the
neonatal intensive care unit (NICU) and during surgery or magnetic resonance
imaging (MRI) are lacking. The aim of this study is to determine the proportion
of infants normothermic (36.5-37.5 degrees C) on return to NICU after management
during surgery and MRI, and during standard clinical care in both environments.
METHODS: Sixty-two newborns requiring either surgery in the operating theatre
(OT) (n = 41) or an MRI scan (n = 21) at the Royal Children's Hospital
(Melbourne) NICU were prospectively studied. Core temperature, along with
cardiorespiratory parameters, was continuously measured from 15 min prior to
leaving the NICU until 60 min after returning. Passive and active warming (intra
operatively) was at clinician discretion. RESULTS: The study reported 90% of
infants were normothermic before leaving NICU: 86% (MRI) and 93% (OT). Only 52%
of infants were normothermic on return to NICU (relative risk (RR) 1.75; 95%
confidence interval (CI) 1.39-2.31; number needed to harm (NNH) 2.6). Between
departure from the NICU and commencement of surgery, core temperature decreased
by mean 0.81 degrees C (95% CI 0.30-1.33; P = 0.0001, analysis of variance), with
only 24% of infants normothermic when surgery began (P < 0.0001; RR 3.80 (95% CI
2.33-6.74); NNH 1.5). After an MRI, infants were a mean 0.41 degrees C (95% CI
0.16-0.67) colder than immediately before entering the scanner (P = 0.001,
analysis of variance), with only 43% being normothermic (P = 0.003; RR 2.11 (95%
CI 1.35-3.74); NNH 2.1). CONCLUSION: Unintentional hypothermia is a common
occurrence during surgery in the OT and MRI in neonates, indicating that evidence
based warming strategies to prevent hypothermia should be developed.
PMID- 29330888
TI - McRoberts' maneuver increases fetal head angle of progression in second stage of
labor.
PMID- 29330887
TI - Loss of VAMP5 in mice results in duplication of the ureter and insufficient
expansion of the lung.
AB - BACKGROUND: Vesicle-associated membrane protein 5 (VAMP5) is a member of the
SNARE protein family, which regulates the docking and fusion of membrane vesicles
within cells. Previously, we reported ubiquitous expression of VAMP5 proteins in
various organs except the brain and small intestine. However, the precise roles
of VAMP5 in each organ remain unclear. To explore the roles of VAMP5 in vivo, we
generated VAMP5 knockout (KO) mice. RESULTS: VAMP5 KO mice showed low birth rate
and low body weight. KO embryos grew normally in the uterus, and tended to die
around birth. Anatomical analysis revealed that viable KO mice often exhibited
duplication of the ureter, and dead KO mice showed insufficient expansion of the
lung. VAMP5 was localized in the epithelial cells of the ureter and terminal
bronchiole. CONCLUSIONS: VAMP5 KO mice showed a low birth rate and abnormalities
of the urinary and respiratory systems. VAMP5 KO mice died around birth, possibly
due to defects in vesicoureteral flow and breathing. The results presented could
provide a basis for future studies to understand the roles of VAMP5 protein.
Developmental Dynamics 247:754-762, 2018. (c) 2018 Wiley Periodicals, Inc.
PMID- 29330889
TI - Exercise desaturation and oxygen therapy in ILD and COPD: Similarities,
differences and therapeutic relevance.
PMID- 29330890
TI - Audit of referrals for concern regarding labial appearance at the Royal
Children's Hospital: 2000-2012.
AB - AIM: To audit the clinical features and outcomes for all patients referred to our
centre with concerns regarding labial appearance. METHODS: Young females referred
to a paediatric/adolescent gynaecology tertiary centre between 2000 and 2012 with
concerns regarding their labial appearance were retrospectively identified.
Adolescents presenting with anomalies were excluded. Retrospective chart review
was undertaken to identify reasons for referral, patient characteristics, outcome
of referral and concurrent health problems. RESULTS: In total, 46 females
presenting with concerns about labial appearance were identified. Five were
excluded. Median age of the study population was 14.5 years (range 5-21 years).
Only four (9.8%) underwent surgery after a minimum of five consultations each,
with mental health review in three of four cases prior to surgery. None of the 41
patients had documented abnormal labia; however, 6 patients had asymmetry, and 3
had a labial width of >5 cm. Of mothers, 24% (n = 10) raised the initial concern
regarding labial appearance to a physician, of whom, 50% of patients had a
comorbid condition. In total, 70.7% initially reported interference with daily
activities, and 87.8% were reassured following discussion. CONCLUSIONS: With
appropriate education and counselling, the majority of girls with concerns
regarding labial appearance can be managed without surgery. Overall, our data
support current international policy that female cosmetic genital surgery not be
performed in mature minors unless there are specific indications. More research
about characteristics of patients referred with labial concerns, definition of
labial size and long-term satisfaction of conservative versus surgical methods is
necessary to determine the best approach.
PMID- 29330891
TI - Why do African Americans have a higher risk for cerebral disease?
PMID- 29330892
TI - Ophthalmic artery Doppler for prediction of pre-eclampsia: systematic review and
meta-analysis.
AB - OBJECTIVE: To determine the accuracy of ophthalmic artery Doppler in pregnancy
for the prediction of pre-eclampsia (PE). METHODS: MEDLINE, EMBASE, CINAHL and
The Cochrane Library were searched for relevant citations without language
restrictions. Two reviewers independently selected studies that evaluated the
accuracy of ophthalmic artery Doppler to predict the development of PE and
extracted data to construct 2 * 2 tables. Individual patient data were obtained
from the authors if available. A bivariate random-effects model was used for the
quantitative synthesis of data. Logistic regression analysis was employed to
generate receiver-operating characteristics (ROC) curves and obtain optimal cut
offs for each investigated parameter, and a bivariate analysis was employed using
predetermined cut-offs to obtain sensitivity and specificity values and generate
summary ROC curves. RESULTS: A total of 87 citations matched the search criteria
of which three studies, involving 1119 pregnancies, were included in the
analysis. All included studies had clear description of the index and reference
tests, avoidance of verification bias and adequate follow-up. Individual patient
data were obtained for all three included studies. First diastolic peak velocity
of ophthalmic artery Doppler at a cut-off of 23.3 cm/s showed modest sensitivity
(61.0%; 95% CI, 44.2-76.1%) and specificity (73.2%; 95% CI, 66.9-78.7%) for the
prediction of early-onset PE (area under the ROC curve (AUC), 0.68; 95% CI, 0.61
0.76). The first diastolic peak velocity had a much lower sensitivity (39.0%; 95%
CI, 20.6-61.0%), a similar specificity (73.2%; 95% CI, 66.9-78.7%) and a lower
AUC (0.58; CI, 0.52-0.65) for the prediction of late-onset PE. The pulsatility
index of the ophthalmic artery did not show a clinically useful sensitivity or
specificity at any cut-off for early- or late-onset PE. Peak ratio above 0.65
showed a similar diagnostic accuracy to that of the first diastolic peak velocity
with an AUC of 0.67 (95% CI, 0.58-0.77) for early-onset PE and 0.57 (95% CI, 0.51
0.63) for late-onset disease. CONCLUSIONS: Ophthalmic artery Doppler is a simple,
accurate and objective technique with a standalone predictive value for the
development of early-onset PE equivalent to that of uterine artery Doppler
evaluation. The relationship between ophthalmic Doppler indices and PE cannot be
a consequence of trophoblast invasion and may be related to maternal hemodynamic
adaptation to pregnancy. The findings of this review justify efforts to elucidate
the effectiveness and underlying mechanism whereby two seemingly unrelated
maternal vessels can be used for the prediction of a disease considered a
'placental disorder'. Copyright (c) 2018 ISUOG. Published by John Wiley & Sons
Ltd.
PMID- 29330893
TI - Mitogenomic differences between the normal and tumor cells of colorectal cancer
patients.
AB - So far, a reliable spectrum of mitochondrial DNA mutations in colorectal cancer
cells is still unknown, and neither is their significance in carcinogenesis.
Indeed, it remains debatable whether mtDNA mutations are "drivers" or
"passengers" of colorectal carcinogenesis. Thus, we analyzed 200 mitogenomes from
normal and cancer tissues of 100 colorectal cancer patients. Minority variant
mutations were detected at the 1% level. We showed that somatic mutations
frequently occur in colorectal cancer cells (75%) and are randomly distributed
across the mitochondrial genome. Mutational signatures of somatic mitogenome
mutations suggest that they might arise through nucleotide deamination due to
oxidative stress. The majority of somatic mutations localized within the coding
region (in positions not known from the human phylogeny) and was potentially
pathogenic to cell metabolism. Further analysis suggested that the relaxation of
negative selection in the mitogenomes of colorectal cancer cells may allow
accumulation of somatic mutations. Thus, a shift in glucose metabolism from
oxidative phosphorylation to glycolysis may create advantageous conditions for
accumulation of mtDNA mutations. Considering the fact that the presence of
somatic mtDNA mutations was not associated with any clinicopathological features,
we suggested that mtDNA somatic mutations are "passengers" rather than the cause
of colorectal carcinogenesis.
PMID- 29330894
TI - Structure, function and evolution of the hemerythrin-like domain superfamily.
AB - Hemerythrin-like proteins have generally been studied for their ability to
reversibly bind oxygen through their binuclear nonheme iron centers. However, in
recent years, it has become increasingly evident that some members of the
hemerythrin-like superfamily also participate in many other biological processes.
For instance, the binuclear nonheme iron site of YtfE, a hemerythrin-like protein
involved in the repair of iron centers in Escherichia coli, catalyzes the
reduction of nitric oxide to nitrous oxide, and the human F-box/LRR-repeat
protein 5, which contains a hemerythrin-like domain, is involved in intracellular
iron homeostasis. Furthermore, structural data on hemerythrin-like domains from
two proteins of unknown function, PF0695 from Pyrococcus furiosus and NMB1532
from Neisseria meningitidis, show that the cation-binding sites, typical of
hemerythrin, can be absent or be occupied by metal ions other than iron. To
systematically investigate this functional and structural diversity of the
hemerythrin-like superfamily, we have collected hemerythrin-like sequences from a
database comprising fully sequenced proteomes and generated a cluster map based
on their all-against-all pairwise sequence similarity. Our results show that the
hemerythrin-like superfamily comprises a large number of protein families which
can be classified into three broad groups on the basis of their cation
coordinating residues: (a) signal-transduction and oxygen-carrier hemerythrins (H
HxxxE-HxxxH-HxxxxD); (b) hemerythrin-like (H-HxxxE-H-HxxxE); and, (c) metazoan F
box proteins (H-HExxE-H-HxxxE). Interestingly, all but two hemerythrin-like
families exhibit internal sequence and structural symmetry, suggesting that a
duplication event may have led to the origin of the hemerythrin domain.
PMID- 29330896
TI - Goodbye to neuromuscular images.
PMID- 29330895
TI - Effect of local scrotal heating on the expression of tight junction-associated
molecule Occludin in boar testes.
AB - The aim of this study was to determine whether local scrotal heating (42 degrees
C, for 1 hr) had an effect on the expression of tight junction (TJ)-associated
molecule Occludin in boar testes. Adult boars (Landrace, n = 6) were used and
randomly divided into two groups (n = 3 each). Three boars were given local
scrotal exposure to 42 degrees C for approximately 1 h with a home-made electric
blanket of controlled temperature as local scrotal heating group, the other three
boars received no heat treatment and were left at standard room temperature as
control group. After 6 hr, all boars were castrated and the testes were
harvested. qRT-PCR, Western blotting and immunohistochemistry were used to
explore the expression and localization of Occludin. qRT-PCR and Western blotting
showed that the protein and mRNA levels of Occludin significantly decreased in
local scrotal heating group as compared to the control. Furthermore,
immunoreactivity staining of Occludin was localized at the sites of the blood
testis barrier (BTB) and formed an almost consecutive and strong immunoreactivity
strand in the control, while Occludin was limited to Sertoli cells (SCs) and no
obvious immunoreactivity strand was present in local scrotal heating group. These
data indicated that local scrotal heating decreased the expression of TJ
associated molecule Occludin, which may be involved in heat-induced
spermatogenesis damage.
PMID- 29330897
TI - Cyclodextrin-assisted dispersive liquid-liquid microextraction for the
preconcentration of carbamazepine and clobazam with subsequent sweeping micellar
electrokinetic chromatography.
AB - A new version of dispersive liquid-liquid microextraction, namely, cyclodextrin
assisted dispersive liquid-liquid microextraction, with subsequent sweeping
micellar electrokinetic chromatography has been developed for the
preconcentration and sensitive detection of carbamazepine and clobazam. alpha
Cyclodextrin and chloroform were used as the dispersive agent and extraction
solvent, respectively. After the extraction, carbamazepine and clobazam were
analyzed using micellar electrokinetic chromatography with ultraviolet detection.
The detection sensitivity was further enhanced using the sweeping technique.
Under optimal extraction and stacking conditions, the calibration curves of
carbamazepine and clobazam were linear over a concentration range of 2.0-200.0
ng/mL. The method detection limits at a signal-to-noise ratio of 3 were 0.6 and
0.5 ng/mL with sensitivity enhancement factors of 3575 and 4675 for carbamazepine
and clobazam, respectively. This developed method demonstrated high sensitivity
enhancement factors and was successfully applied to the determination of
carbamazepine and clobazam in human urine samples. The precision and accuracy for
urine samples were less than 4.2 and 6.9%, respectively.
PMID- 29330898
TI - Determination of phthalate esters in soil using a quick, easy, cheap, effective,
rugged, and safe method followed by GC-MS.
AB - A quick, easy, cheap, effective, rugged, and safe procedure was designed to
extract pesticide residues from fruits and vegetables with a high percentage of
water. It has not been used extensively for the extraction of phthalate esters
from sediments, soils, and sludges. In this work, this procedure was combined
with gas chromatography with mass spectrometry to determine 16 selected phthalate
esters in soil. The extraction efficiency of the samples was improved by
ultrasonic extraction and dissolution of the soil samples in ultra-pure water,
which promoted the dispersion of the samples. Furthermore, we have simplified the
extraction step and reduced the risk of organic solvent contamination by
minimizing the use of organic solvents. Different extraction solvents and clean
up adsorbents were compared to optimize the procedure. Dichloromethane/n-hexane
(1:1, v/v) and n-hexane/acetone (1:1, v/v) were selected as the extractants from
the six extraction solvents tested. C18/primary secondary amine (1:1, m/m) was
selected as the sorbent from the five clean-up adsorbents tested. The recoveries
from the spiked soils ranged from 70.00 to 117.90% with relative standard
deviation values of 0.67-4.62%. The proposed approach was satisfactorily applied
for the determination of phthalate esters in 12 contaminated soil samples.
PMID- 29330899
TI - Retrograde transmitral paravalvular leak closure through an antegrade transseptal
approach: A novel technique.
AB - Mitral paravalvular leak (PVL) remains a well-known complication after mitral
valve replacement. Since the first report over 25 years ago, several catheter
based PVL closure techniques have been described. Most of these comprise of
either an antegrade transseptal approach, or a retrograde transaortic or
transapical approach. We herein report a novel percutaneous mitral PVL closure
technique that was safely and successfully performed after failed attempt using a
conventional antegrade approach.
PMID- 29330900
TI - Overexpression of microRNA408 enhances photosynthesis, growth, and seed yield in
diverse plants.
AB - The ability of a plant to produce grain, fruit, or forage depends ultimately on
photosynthesis. There have been few attempts, however, to study microRNAs, which
are a class of endogenous small RNAs post-transcriptionally programming gene
expression, in relation to photosynthetic traits. We focused on miR408, one of
the most conserved plant miRNAs, and overexpressed it in parallel in Arabidopsis,
tobacco, and rice. The transgenic plants all exhibited increased copper content
in the chloroplast, elevated abundance of plastocyanin, and an induction of
photosynthetic genes. By means of gas exchange and optical spectroscopy analyses,
we showed that higher expression of miR408 leads to enhanced photosynthesis
through improving efficiency of irradiation utilization and the capacity for
carbon dioxide fixation. Consequently, miR408 hyper-accumulating plants exhibited
higher rate of vegetative growth. An enlargement of seed size was also observed
in all three species overproducing miR408. Moreover, we conducted a 2-year-two
location field trial and observed miR408 overexpression in rice significantly
increased yield, which was primarily attributed to an elevation in grain weight.
Taken together, these results demonstrate that miR408 is a positive regulator of
photosynthesis and that its genetic engineering is a promising route for
enhancing photosynthetic performance and yield in diverse plants.
PMID- 29330901
TI - Floral contrivances and specialised pollination mechanism strongly influence
mixed mating in Wrightia tomentosa (Apocynaceae).
AB - Reproductive success of a plant species is largely influenced by the outcome of
mating pattern in a population. It is believed that a significantly larger
proportion of animal-pollinated plants have evolved a mixed-mating strategy, the
extent of which may vary among species. It is thus pertinent to investigate the
key contributors to mating success, especially to identify the reproductive
constraints in depauperate populations of threatened plant species. We examined
the contribution of floral architecture, pollination mechanism and breeding
system on the extent of outcrossing rate in a near-threatened tree species,
Wrightia tomentosa. The breeding system was ascertained from controlled
pollination experiments. In order to determine outcrossing rate, 60 open
pollinated progeny were analysed using an AFLP markers. Although the trees are
self-compatible, herkogamy and compartmentalisation of pollen and nectar in
different chambers of the floral tube effectively prevent spontaneous autogamy.
Pollination is achieved through specialised interaction with moths. Differential
foraging behaviour of settling moths and hawkmoths leads to different proportions
of geitonogamous and xenogamous pollen on the stigma. However, most open
pollinated progeny were the result of xenogamy (outcrossing rate, tm = 0.68). The
study shows that floral contrivances and pollination system have a strong
influence on mating pattern. The differential foraging behaviour of the
pollinators causes deposition of a mixture of self- and cross-pollen to produce a
mixed brood. Inbreeding depression and geitonogamy appear to play a significant
role in sustaining mixed mating in this species.
PMID- 29330902
TI - Conformers, properties, and docking mechanism of the anticancer drug docetaxel:
DFT and molecular dynamics studies.
AB - The conformational structures and properties of the anticancer drug docetaxel
(DTX) are studied theoretically. A total of 3888 trial structures were initially
generated by all combinations of internal single-bond rotamers and screened with
the B3LYP/3-21G* method. A total of 31 unique conformers were further optimized
at the B3LYP/6-311G* method. Their relative energies, dipole moments, rotational
constants, and harmonic vibrational frequencies were predicted. Single-point
relative energies were then determined at the M06-L/6-311G(2df,p) level. The UV
spectrum of the lowest-lying DTX conformer in methanol was investigated with the
TD-CAM-B3LYP/6-311 + G(2df,p) method. The 31 unique DTX structures are mainly
docked at three different sites within beta-tubulin. Based on the results of
molecular docking and double-float MD simulations, the lowest-lying DTX conformer
consistently exhibits good docking performance with beta-tubulin. We identified
the residues LYS299, ARG215, GLN294, LEU275, THR216, GLU290, PRO274, and THR276
on beta-tubulin as active sites forming a binding pocket responsible for locking
DTX within beta-tubulin to make the combination more stable. The RMSD values show
that the predicted complexes are favorable, and the SASA analysis shows that the
hydrophilic properties of DTX are better than paclitaxel. (c) 2018 Wiley
Periodicals, Inc.
PMID- 29330903
TI - Lack of correlation between pollen aperture number and environmental factors in
pansies (Viola L., sect. Melanium Ging.) - pollen heteromorphism re-examined.
AB - The development of different pollen morphs by one specimen - pollen
heteromorphism - occurs in ca. one-third species of the genus Viola. Melanium
section species (pansies) stand out in producing the widest range of apertures
among Viola species. Aperture number decreases with elevation increase, and
faster germination of five-aperturate pollen as compared with three-aperturate
has previously been postulated. We re-examined pollen heteromorphism in the
context of its viability, and made correlations with elevation (>1500 m a.s.l.
versus <1500 m a.s.l.), soil type (metalliferous versus non-metalliferous; MET
versus NMET) and chromosome number based on selected study criteria of ca. 20%
karyologically and morphologically strongly differentiated but genetically
closely related pansies. A total of 79% of analysed species were heteromorphic,
forming three- to six-colp or ate pollen per individual flower. Mean aperture
number and pollen viability were not affected by soil type (MET versus NMET).
Mean aperture number was also not influenced by elevation or species chromosome
number. Positive correlations were established between aperture number and pollen
viability, negative between pollen viability and elevation (increasing altitude
of 100 m decreased pollen viability by 0.4%) and lack of correlation between
chromosome number and pollen viability. The varied frequencies of different
pollen morphs among species are not under the general pressure of ecological
conditions, as previously postulated for the species of Melanium section. Rather,
this trait in pansies, similar to other floral characters (e.g. long, curved
nectar spur, 'landing platform', posterior petals with nectar guides), is
adaptive but dependent on the breeding system (inbreeding versus outbreeding) of
the individual species.
PMID- 29330905
TI - Evidence-based consensus on opportunistic infections in inflammatory bowel
disease.
PMID- 29330904
TI - Testing a chemical series inspired by plant stress oxylipin signalling agents for
herbicide safening activity.
AB - BACKGROUND: Herbicide safening in cereals is linked to a rapid xenobiotic
response (XR), involving the induction of glutathione transferases (GSTs). The XR
is also invoked by oxidized fatty acids (oxylipins) released during plant stress,
suggesting a link between these signalling agents and safening. To examine this
relationship, a series of compounds modelled on the oxylipins 12-oxophytodienoic
acid and phytoprostane 1, varying in lipophilicity and electrophilicity, were
synthesized. Compounds were then tested for their ability to invoke the XR in
Arabidopsis and protect rice seedlings exposed to the herbicide pretilachlor, as
compared with the safener fenclorim. RESULTS: Of the 21 compounds tested, three
invoked the rapid GST induction associated with fenclorim. All compounds
possessed two electrophilic carbon centres and a lipophilic group characteristic
of both oxylipins and fenclorim. Minor effects observed in protecting rice
seedlings from herbicide damage positively correlated with the XR, but did not
provide functional safening. CONCLUSION: The design of safeners based on the
characteristics of oxylipins proved successful in deriving compounds that invoke
a rapid XR in Arabidopsis but not in providing classical safening in a cereal.
The results further support a link between safener and oxylipin signalling, but
also highlight species-dependent differences in the responses to these compounds.
(c) 2018 The Authors. Pest Management Science published by John Wiley & Sons Ltd
on behalf of Society of Chemical Industry.
PMID- 29330907
TI - Tubular adenomas with clear cell change in the colorectum: A case with four
lesions and a review of the literature.
PMID- 29330909
TI - Catalytic and Atom-Economic Csp3 -Csp3 Bond Formation: Alkyl Tantalum Ureates for
Hydroaminoalkylation.
AB - Atom-economic and regioselective Csp3 -Csp3 bond formation has been achieved by
rapid C-H alkylation of unprotected secondary arylamines with unactivated
alkenes. The combination of Ta(CH2 SiMe3 )3 Cl2 , and a ureate N,O-chelating
ligand salt gives catalytic systems prepared in situ that can realize high yields
of beta-alkylated aniline derivatives from either terminal or internal alkene
substrates. These new catalyst systems realize C-H alkylation in as little as one
hour and for the first time a 1:1 stoichiometry of alkene and amine substrates
results in high yielding syntheses of isolated amine products by simple
filtration and concentration.
PMID- 29330908
TI - Defining expanded areas in EBUS sampling: EBUS guided trans- and intra-pulmonary
artery needle aspiration, with review of transvascular EBUS.
AB - BACKGROUND: Endobronchial Ultrasound-guided Transbronchial Needle Aspiration
(EBUS-TBNA) has revolutionized the diagnostic approach to mediastinal diseases.
Lesions located lateral to the pulmonary artery (trans-PA, Station 5), or in the
lumen of the PA (intra-PA) are in the 'blind-spot' of EBUS. OBJECTIVES: We
describe a case series where EBUS guided trans-pulmonary or intra-pulmonary
aspiration (EBUS-TIPNA) was used for diagnosis. METHODS: Retrospective analysis
of 10 patients who had EBUS-TIPNA over 3 years in 2 centres. The inclusion
criteria included patients with station 5 lesions, or intrapulmonary artery
lesions, where no other option was possible. RESULTS: The study included 4 males
and 6 females, mean age 52 years, with 7 trans-PA and 3 intra-PA lesions.
Adequacy was seen in 10/10, and a definitive diagnosis was made in 9/10 patients.
There were no procedure-related complications. CONCLUSION: EBUS-TIPNA can be done
as a safe and successful procedure and adds to the armamentarium of Convex Probe
EBUS (CP-EBUS), in carefully selected patients.
PMID- 29330906
TI - Generating retinoic acid gradients by local degradation during craniofacial
development: One cell's cue is another cell's poison.
AB - Retinoic acid (RA) is a vital morphogen for early patterning and organogenesis in
the developing embryo. RA is a diffusible, lipophilic molecule that signals via
nuclear RA receptor heterodimeric units that regulate gene expression by
interacting with RA response elements in promoters of a significant number of
genes. For precise RA signaling, a robust gradient of the morphogen is required.
The developing embryo contains regions that produce RA, and specific
intracellular concentrations of RA are created through local degradation mediated
by Cyp26 enzymes. In order to elucidate the mechanisms by which RA executes
precise developmental programs, the kinetics of RA metabolism must be clearly
understood. Recent advances in techniques for endogenous RA detection and
quantification have paved the way for mechanistic studies to shed light on
downstream gene expression regulation coordinated by RA. It is increasingly
coming to light that RA signaling operates not only at precise concentrations but
also employs mechanisms of degradation and feedback inhibition to self-regulate
its levels. A global gradient of RA throughout the embryo is often found
concurrently with several local gradients, created by juxtaposed domains of RA
synthesis and degradation. The existence of such local gradients has been found
especially critical for the proper development of craniofacial structures that
arise from the neural crest and the cranial placode populations. In this review,
we summarize the current understanding of how local gradients of RA are
established in the embryo and their impact on craniofacial development.
PMID- 29330911
TI - Prognostic significance of arterial stiffness and osteoprotegerin in patients
with stable coronary artery disease.
AB - BACKGROUND: Arterial stiffness and vascular calcification significantly
contribute to coronary atherosclerosis progression. The prognostic value of
increased arterial stiffness and vascular calcification in subjects with stable
coronary artery disease (CAD) after percutaneous coronary intervention(PCI) is
currently under question. MATERIALS AND METHODS: We randomly enrolled 262
patients with stable CAD 1 month after successful PCI. Carotid-femoral pulse wave
velocity (PWV) was measured as a well-established index of central aortic
stiffness. Osteoprotegerin (OPG) plasma levels were measured as a biomarker of
vascular calcification. Patients were followed up prospectively up to 52 months.
The primary endpoint was the composite of death from cardiovascular causes,
myocardial infarction, stroke or hospitalization for cardiovascular causes.
RESULTS: During the follow-up period, 48 patients presented the primary composite
endpoint. Subjects who presented the primary endpoint, compared to subjects free
of cardiovascular events, had significantly increased PWV (9.45 +/- 2.19 m/s vs
8.73 +/- 2.07 m/s, P = .04) and OPG levels (4.21 +/- 2.19 pmol/L vs 3.18 +/- 1.74
pmol/L, P = .003). Survival analysis indicated that PWV predicted adverse cardiac
events MACE (Hazard ratio = 1.29 95%CI: 1.07-1.57, P = .008) independently from
confounders such as age, sex, smoking habits, ejection fraction, extent of
coronary artery disease, hypertension and diabetes mellitus. Interestingly, for
every increase in pulse wave velocity by 1 m/s, there is an anticipated increase
in the risk of major adverse cardiovascular event (MACE) by 29%. CONCLUSIONS:
These findings extend the current knowledge concerning the role of arterial
stiffness as powerful biomarkers in cardiovascular disease. Measurement of PWV
might have a role in ascertaining prognosis and managing treatment in patients
with stable CAD after PCI.
PMID- 29330912
TI - High-capacity protein A affinity chromatography for the fast quantification of
antibodies: Two-wavelength detection expands linear range.
AB - The high-throughput analysis of antibodies from processes can be enhanced when
the linear range is expanded and sample preparation is kept to a minimum. We
developed a fast chromatography method based on a hexameric variant of
staphylococcal protein A immobilized on Toyopearl matrix, TSK 5 PW using two
wavelengths. A protocol with 5 min runtime and a single-wavelength detection at
280 nm yielded an upper limit of quantification of 2.10 mg/mL and a lower limit
of quantification of 0.06 mg/mL. The optimized method with a runtime of 2 min and
two-wavelength detection at 280 and 300 nm allowed us to span a valid
concentration range of 0.01-5.20 mg/mL using two calibration curves. Sample
selectivity was tested using mock supernatant mixed with antibody concentrations
of 0.1-2.1 mg/mL, sample stability in the autosampler was shown for at least 24
h. We also tested the capabilities of the method to determine purity of an
antibody sample by calculating the ratio of peak area of elution to peak area of
flow-through, which correlated well with the expected purity. The method will be
very useful for process development and in-process control, spanning
concentrations from seed fermentation to harvest and purification.
PMID- 29330913
TI - The mechanism of diflufenican resistance and its inheritance in oriental mustard
(Sisymbrium orientale L.) from Australia.
AB - BACKGROUND: An oriental mustard population (P3) collected near Quambatook,
Victoria was identified as being resistant to diflufenican by screening with the
field rate (200 g a.i. ha-1 ) of the herbicide. The mechanism(s) of diflufenican
resistance and its inheritance in this population were therefore investigated.
RESULTS: Dose-response experiments confirmed that population P3 was 140-fold more
resistant to diflufenican than susceptible populations, as determined by the
comparison of 50% lethal (LD50 ) values. The phytoene desaturase (PDS) gene from
five individuals each of the S1 [susceptible (S)] and P3 [resistant (R)]
populations was sequenced, and a substitution of valine for leucine at position
526 (Leu-526-Val) was detected in all five individuals of P3, but not in the S1
population. Inheritance studies showed that diflufenican resistance is encoded in
the nuclear genome and is dominant, as the response to diflufenican at 200 g a.i.
ha-1 of F1 families was equivalent to that of the resistant biotype. The
segregation of F2 phenotypes fitted a 3:1 inheritance model. Segregation of 42 F2
individuals by genotype sequencing fitted a 1:2:1 (ss:Rs:RR) ratio. CONCLUSION:
Resistance to diflufenican in oriental mustard is conferred by the Leu-526-Val
mutation in the PDS gene. Inheritance of resistance is managed by a single gene
with high levels of dominance. (c) 2018 Society of Chemical Industry.
PMID- 29330914
TI - Stereodivergent Synthesis of Tetrahydrofuroindoles through Pd-Catalyzed
Asymmetric Dearomative Formal [3+2] Cycloaddition.
AB - A stereodivergent synthesis of tetrahydrofuroindoles through palladium-catalyzed
asymmetric dearomative formal [3+2] cycloaddition of nitroindoles with
epoxybutenes was developed. The polarity of the solvent was found to play a key
role in the diastereoselectivity. In toluene, good to excellent yields (70-99 %),
diastereoselectivity (87/13->95/5 d.r.), and enantioselectivity (85/15-94/6 e.r.)
were obtained, regardless of the properties of the substituents on nitroindoles.
In acetonitrile, tetrahydrofuroindoles of a different diastereoisomer were
produced with good to excellent yields (75-98 %) and stereoselectivity (78/22
93/7 d.r., 93/7-99/1 e.r.). Mechanistic studies were conducted to illustrate the
origin of the diastereodivergency. The kinetic experiments indicate that the rate
determining step of this reaction is different in different solvents. ESI-MS
experiments also support the existence of key palladium complex intermediates and
the catalytic cycle of the reaction.
PMID- 29330915
TI - Effects of seed mixture sowing with resistant and susceptible rice on population
dynamics of target planthoppers and non-target stemborers and leaffolders.
AB - BACKGROUND: The widespread planting of insect-resistant crops has caused a
dramatic shift in agricultural landscapes, thus raising concerns about the
potential impact on both target and non-target pests worldwide. In this study, we
examined the potential effects of six seed mixture ratios of insect-resistance
dominance [100% (R100), 95% (S05R95), 90% (S10R90), 80% (S20R80), 60% (S40R60),
and 0% (S100)] on target and non-target pests in a 2-year field trial in southern
China. RESULTS: The occurrence of the target pests Nilaparvata lugens and
Sogatella furcifera decreased with an increase in the ratio of resistant rice,
and mixture ratios with >=90% resistant rice significantly increased the pest
suppression efficiency, with the lowest occurrences of the non-target pests
Sesamia inferens, Chilo suppressalis and Cnaphalocrocis medinalis for S100 and
S10R90 seed mixture ratios. Furthermore, there were no significant differences in
the 1000-grain dry weight and grain yield between R100 and other treatments with
>=80% resistant seeds in the mixture (S20R80, S10R90 and S05R95). CONCLUSION:
S10R90 produced a good yield and provided the most effective control of both
target and non-target pests, with the potential to significantly reduce the
application of chemical pesticides for integrated pest management in paddy
fields. It is further presumed that the strategy of seed mixture with resistant
and susceptible rice would be advantageous for rice yield stability. (c) 2018
Society of Chemical Industry.
PMID- 29330916
TI - Separation of three polar compounds from Rheum tanguticum by high-speed
countercurrent chromatography with an ethyl acetate/glacial acetic acid/water
system.
AB - The separation of polar compounds by high-speed countercurrent chromatography is
still regarded as a challenge. In this study, an efficient strategy for the
separation of three polar compounds from Rheum tanguticum has been successfully
conducted by using high-speed countercurrent chromatography. X-5 macroporous
resin chromatography was used for the fast enrichment of the target compounds.
Then, the target fraction was directly introduced into high-speed countercurrent
chromatography for separation using ethyl acetate/glacial acetic acid/water
(100:1:100, v/v/v) as the solvent system. Consequently, three polar compounds
including gallic acid, catechin, and gallic acid 4-O-beta-d-(6'-O-galloyl)
glucoside were obtained with purities higher than 98%. The results showed glacial
acetic acid could be such an appropriate regulator for the ethyl acetate/water
system. This study provides a reference for the separation of polar compounds
from natural products by high-speed countercurrent chromatography.
PMID- 29330917
TI - Mitochondrial respiratory capacity remains stable despite a comprehensive and
sustained increase in insulin sensitivity in obese patients undergoing gastric
bypass surgery.
AB - AIM: It has been proposed, but not yet demonstrated by convincing evidence in
published articles, that insulin resistance and mitochondrial respiratory
function are causally related physiological phenomena. Here, we tested the
prediction that weight loss-induced increase in insulin sensitivity will
correlate with a corresponding change in mitochondrial respiratory capacity over
the same time period. METHODS: Insulin sensitivity was evaluated using the
hyperinsulinaemic-euglycaemic clamp technique, and skeletal muscle mitochondrial
respiratory capacity was evaluated by high-resolution respirometry in 26 patients
with obesity. Each experiment was performed ~2 months and 1-2 weeks before, and
~4 and ~19 months after Roux-en-Y gastric bypass (RYGB) surgery. RESULTS: A
substantial weight loss was observed in all patients, and insulin sensitivity
increased in all patients over the 21-months time period of the study. In
contrast, skeletal muscle mitochondrial respiratory capacity, intrinsic
mitochondrial respiratory capacity and mitochondrial content remained unchanged
over the same time period. CONCLUSION: Among obese patients with and without type
2 diabetes undergoing RYGB surgery, intrinsic mitochondrial respiratory capacity
in skeletal muscle is not correlated with insulin sensitivity before or after the
surgical intervention. Mitochondrial respiratory function may not be germane to
the pathophysiology and/or aetiology of obesity and/or type 2 diabetes.
PMID- 29330918
TI - Leptosphaeria maculans AvrLm9: a new player in the game of hide and seek with
AvrLm4-7.
AB - Blackleg disease of Brassica napus caused by Leptosphaeria maculans (Lm) is
largely controlled by the deployment of race-specific resistance (R) genes.
However, selection pressure exerted by R genes causes Lm to adapt and give rise
to new virulent strains through mutation and deletion of effector genes.
Therefore, a knowledge of effector gene function is necessary for the effective
management of the disease. Here, we report the cloning of Lm effector AvrLm9
which is recognized by the resistance gene Rlm9 in B. napus cultivar Goeland.
AvrLm9 was mapped to scaffold 7 of the Lm genome, co-segregating with the
previously reported AvrLm5 (previously known as AvrLmJ1). Comparison of AvrLm5
alleles amongst the 37 re-sequenced Lm isolates and transgenic complementation
identified a single point mutation correlating with the AvrLm9 phenotype.
Therefore, we renamed this gene as AvrLm5-9 to reflect the dual specificity of
this locus. Avrlm5-9 transgenic isolates were avirulent when inoculated on the B.
napus cultivar Goeland. The expression of AvrLm5-9 during infection was monitored
by RNA sequencing. The recognition of AvrLm5-9 by Rlm9 is masked in the presence
of AvrLm4-7, another Lm effector. AvrLm5-9 and AvrLm4-7 do not interact, and
AvrLm5-9 is expressed in the presence of AvrLm4-7. AvrLm5-9 is the second Lm
effector for which host recognition is masked by AvrLm4-7. An understanding of
this complex interaction will provide new opportunities for the engineering of
broad-spectrum recognition.
PMID- 29330919
TI - Meta-analysis of laparoscopic versus open liver resection for hepatocellular
carcinoma.
AB - AIM: The aim of this study was to evaluate the surgical safety and effectiveness
of laparoscopic hepatectomy (LH) in short- and long-term outcomes compared to
open hepatectomy (OH) in patients treated for hepatocellular carcinoma (HCC).
METHODS: An electronic search of reports published before August 2017 was carried
out to identify comparative studies evaluating LH versus OH for HCC. RESULTS: A
total of 5889 patients (2421 underwent LH; 3468 underwent OH) were included in
our meta-analysis from 47 studies. Laparoscopic hepatectomies were associated
with favorable outcomes in terms of operative blood loss (mean difference [MD],
147.27; 95% confidence interval [CI], -217.00, -77.55), blood transfusion
requirement (odds ratio [OR], 0.51; 95% CI, 0.40, 0.65), pathologic resection
margins (MD, 0.07; 95% CI, 0.02, 0.12; P = 0.01), R0 resection rate (OR, 1.34;
95% CI, 0.98, 1.84; P = 0.07), and length of hospital stay (MD, -5.13; 95%
confidence interval, -6.23, -4.03). There were no differences between the groups
in overall survival (OS) at 1 year (OR, 1.41; 95% CI, 1.00, 1.98), 3 years (OR,
1.12; 95% CI, 0.93, 1.36), or 5 years (OR, 1.18; 95% CI, 0.94, 1.46), in disease
free survival (DFS) at 1 (OR, 1.19; 95% CI, 0.94, 1.51), 3 years (OR, 1.07; 95%
CI, 0.86, 1.33), or 5 years (OR, 1.13; 95% CI, 0.92, 1.40), or in recurrence (OR,
0.90; 95% CI, 0.74, 1.08). CONCLUSION: Compared to OH, LH is superior in terms of
lower intraoperative blood loss and the requirement for blood transfusion, larger
pathologic resection margins, increased R0 resection rates, and shorter length of
hospital stay. Laparoscopic hepatectomy and OH have similar OS, DFS, and
recurrence.
PMID- 29330920
TI - Macronutrient and fibre intake of young Spanish children with reference to their
in utero growth status: Are they eating a healthy diet?
AB - AIM: To compare macronutrient and fibre intake by pre-school children born with
intra-uterine growth restriction (IUGR) or as appropriate for gestational age
(AGA) and to compare their intake with paediatric nutritional recommendations for
identification of potential areas of modification during early life. METHODS: A
parental 3-day dietary record was obtained for children of age 1-6 years, born at
Hospital Clinic, Barcelona, Spain (2002-2007) with IUGR (n = 37) or AGA (n = 53).
Mean nutrient intake (adjusted for body mass index), nutrient adequacy ratios
(NAR) and percentage of energy intake (EI%) were compared. RESULTS: Macronutrient
and fibre intake of the two groups did not differ significantly. However, IUGR
children showed significantly higher than the recommended levels of protein EI%
(18 (95% confidence interval (CI) 16-19)), NAR for saturated fatty acids (SFAs)
(1.2 (95% CI 1.1-1.5)) and NAR for carbohydrate (1.4 (95% CI 1.2-1.6)) and
significantly lower than the recommended levels of NAR for unsaturated fatty
acids (UFAs) (0.6 (95% CI 0.5-0.8)) and for fibre (0.6 (95% CI 0.5-0.8)).
Likewise, children born with AGA showed similar pattern compared to the
recommended levels for protein EI% (17 (95% CI 16-18)), NAR for SFAs (1.3 (95% CI
1.2-1.4)), NAR for UFAs (0.6 (95% CI 0.5-0.7)) and NAR for fibre (0.8 (95% CI 0.7
0.9)). CONCLUSION: Spanish pre-school children consume proteins and SFAs in
abundance and UFAs and fibre in moderation. Reinforcement of healthy eating is
recommended for long-term health benefits, especially for at-risk children born
with IUGR, whose consumption of carbohydrate is additionally greater than that
recommended.
PMID- 29330921
TI - Four and a half domain 2 (FHL2) scaffolding protein is a marker of connective
tissues of developing digits and regulates fibrogenic differentiation of limb
mesodermal progenitors.
AB - Four and a half LIM domain 2 (FHL2) is a multifunctional scaffolding protein of
well-known function regulating cell signalling cascades and gene transcription in
cancer tissues. However, its function in embryonic systems is poorly
characterized. Here, we show that Fhl2 is involved in the differentiation of
connective tissues of developing limb autopod. We show that Fhl2 exhibits
spatially restricted and temporally dynamic expression around the tendons of
developing digits, interphalangeal joint capsules, and fibrous peridigital
tissue. Immunolabelling analysis of the skeletal progenitors identified a
predominant, but not exclusive, cytoplasmic distribution of FHL2 being associated
with focal adhesions and actin cytoskeleton. In the course of chondrogenic
differentiation of cultures of limb skeletal progenitors, the expression of Fhl2
is down-regulated. Furthermore, cultures of skeletal progenitors overexpressing
Fhl2 take on a predominant fibrogenic appearance. Both gain-of-function and loss
of-function experiments in the micromass culture assays revealed a positive
transcriptional influence of Fhl2 in the expression of fibrogenic markers
including Scleraxis, Tenomodulin, Tenascin C, betaig-h3, and Tgif1. We further
show that the expression of Fhl2 is positively regulated by profibrogenic signals
including Tgfbeta2, all-trans-retinoic acid, and canonical Wnt signalling
molecules and negatively regulated by prochondrogenic factors of the bone
morphogenetic protein family. Expression of Fhl2 is also regulated negatively in
immobilized limbs, but this influence appears to be mediated by other connective
tissue markers, such as Tgfbetas and Scleraxis.
PMID- 29330922
TI - 2018 message from the editor in chief-Movement Disorders journal at cruise speed.
PMID- 29330923
TI - Mutant parkin-induced parkinsonism from an electrical point of view: Abnormal
excitatory response to dopamine resolved after substitution.
PMID- 29330924
TI - Erratum.
PMID- 29330925
TI - In Situ Growth of MnO2 Nanosheets on N-Doped Carbon Nanotubes Derived from
Polypyrrole Tubes for Supercapacitors.
AB - Nitrogen-doped porous carbon nanotubes@MnO2 (N-CNTs@MnO2 ) nanocomposites are
prepared through the in situ growth of MnO2 nanosheets on N-CNTs derived from
polypyrrole nanotubes (PNTs). Benefiting from the synergistic effects between N
CNTs (high conductivity and N doping level) and MnO2 nanosheets (high theoretical
capacity), the as-prepared N-CNTs@MnO2 -800 nanocomposites show a specific
capacitance of 219 F g-1 at a current density of 1.0 A g-1 , which is higher than
that of pure MnO2 nanosheets (128 F g-1 ) and PNTs (42 F g-1 ) in 0.5 m Na2 SO4
solution. Meanwhile, the capacitance retention of 86.8 % (after 1000 cycles at 10
A g-1 ) indicates an excellent electrochemical performance of N-CNTs@MnO2
prepared in this work.
PMID- 29330926
TI - Detection of bovine Deltapapillomavirus DNA in peripheral blood of healthy sheep
(Ovis aries).
AB - Blood samples from 65 sheep were tested for the presence of bovine
Deltapapillomavirus (deltaPVs) DNA. The sheep were divided into three groups.
Sheep in groups 1 and 2 were from Sardinia and Campania, respectively, and were
in contact with cattle and grazed on lands contaminated with bracken fern. Sheep
in Group 3 lived in closed pens and had no contact with cattle. These sheep were
fed hay that did not contain bracken fern. Bovine deltaPV E5 DNA was detected in
blood from 24 of 27 (89%) sheep in Group 1. A single bovine deltaPV type was
detected in the blood from nine (33%) sheep, including the detection of bovine
deltaPV-1 DNA in four sheep, bovine deltaPV-2 in four and deltaPV-13 in one
sheep. Two deltaPV types were detected in 33% of the sheep, and three bovine
deltaPV types were detected in 22% of the sheep. Bovine deltaPVs were detected in
17 of 20 (85%) sheep from Group 2. The detection rate by a single deltaPV type
was 40% with just deltaPV-1 DNA amplified from two, just deltaPV-2 DNA from four,
and just deltaPV-13 DNA from two sheep. Two and three deltaPVs were detected in
30% and 15%, respectively. All sequenced amplicons showed a 100% identity with
papillomaviral E5 DNA deposited in GenBank. Bovine deltaPV-14 DNA sequences were
not detected from any sheep. No bovine deltaPV DNA was revealed in blood samples
from sheep in Group 3. The detection of bovine deltaPV DNA in the blood of sheep
means that sheep may be able to be infected by these PVs. This suggests that
bovine deltaPVs could potentially be a previously unrecognized cause of disease
in sheep. Furthermore, it is possible that sheep could act as a reservoir for
these viruses.
PMID- 29330927
TI - Defined Serum-Free Medium for Bioreactor Culture of an Immortalized Human
Erythroblast Cell Line.
AB - Anticipated shortages in donated blood supply have prompted investigation of
alternative approaches for in vitro production of red blood cells (RBCs), such as
expansion of conditional immortalization erythroid progenitors. However, there is
a bioprocessing challenge wherein factors promoting maximal cell expansion and
growth-limiting inhibitory factors are yet to be investigated. The authors use an
erythroblast cell line (ImEry) derived from immortalizing CD71+CD235a+
erythroblast from adult peripheral blood for optimization of expansion culture
conditions. Design of experiments (DOE) is used in media formulation to explore
relationships and interactive effects between factors which affect cell
expansion. Our in-house optimized medium formulation produced significantly
higher cell densities (3.62 +/- 0.055) * 106 cells mL-1 , n = 3) compared to
commercial formulations (2.07 +/- 0.055) * 106 cells mL-1 , n = 3; at 209 h
culture). Culture media costs per unit of blood is shown to have a 2.96-3.09
times cost reduction. As a proof of principle for scale up, ImEry are expanded in
a half-liter stirred-bioreactor under controlled settings. Growth
characteristics, metabolic, and molecular profile of the cells are evaluated.
ImEry has identical O2 binding capacity to adult erythroblasts. Amino acid
supplementation results in further yield improvements. The study serves as a
first step for scaling up erythroblast expansion in controlled bioreactors.
PMID- 29330928
TI - Specific labelling of myonuclei by an antibody against pericentriolar material 1
on skeletal muscle tissue sections.
AB - AIM: Skeletal muscle is a heterogeneous tissue containing several different cell
types, and only about 40%-50% of the cell nuclei within the tissue belong to
myofibres. Existing technology, attempting to distinguish myonuclei from other
nuclei at the light microscopy level, has led to controversies in our
understanding of the basic cell biology of muscle plasticity. This study aims at
demonstrating that an antibody against the protein pericentriolar material 1
(PCM1) can be used to reliably identify myonuclei on histological cross sections
from humans, mice and rats. METHODS: Cryosections were labelled with a polyclonal
antibody against PCM1. The specificity of the labelling for myonuclei was
verified using 3D reconstructions of confocal z-stacks triple-labelled for DNA,
dystrophin and PCM1, and by co-localization with nuclear mCherry driven by the
muscle-specific Alpha-Actin-1 promoter after viral transduction. RESULTS: The
PCM1 antibody specifically labelled all myonuclei, and myonuclei only, in
cryosections of muscles from rats, mice and men. Nuclei in other cell types
including satellite cells were not labelled. Both normal muscles and hypertrophic
muscles after synergist ablation were investigated. CONCLUSION: Pericentriolar
material 1 can be used as a specific histological marker for myonuclei in
skeletal muscle tissue without relying on counterstaining of other structures or
cumbersome and subjective analysis of nuclear positioning.
PMID- 29330929
TI - Adipocytes affect castration-resistant prostate cancer cells to develop the
resistance to cytotoxic action of NK cells with alterations of PD-L1/NKG2D ligand
levels in tumor cells.
AB - BACKGROUND: Obesity affects prostate cancer (PCa) progression, and the
periprostatic adipose tissue adjacent to the prostate is considered a driving
force of disease progression. Adipocytes are the main cell population in adipose
tissues and their paracrine role contributes to PCa progression, however its
implication in modulating immune reactions remains largely unknown. We
investigated the adipocyte role in controlling the susceptibility of castration
resistant PCa (CRPC) cells to the cytotoxic action of natural killer (NK) cells.
METHODS: Using primary NK cells as the NK cell source, NK cell cytotoxicities to
CRPC cells, either control media treated or adipocyte-conditioned media (CM)
treated, were tested in lactate dehydrogenase (LDH) release-based assays. The
levels of programmed death receptor ligand (PD-L1) and NK group 2D (NKG2D)
ligands in adipocyte CM-treated CRPC cells were analyzed in qPCR analyses.
Effects of blocking adipocyte action on altering PD-L1/NKG2D ligand levels and
the susceptibility of CRPC cells to NK cell cytotoxicity were investigated.
RESULTS: We found NK cell cytotoxicity to CRPC cells decreases when tumor cells
are treated with adipocyte CM associated with PD-L1 and NKG2D ligand level
alterations. Further, we discovered that the JAK/Stat3 signaling pathway was
responsible for the adipocyte CM effect. Two adipokine molecules, IL-6 and
leptin, were shown to be important in activation of the JAK/Stat3 signaling in
CRPC cells to modulate the PD-L1/NKG2D ligand level alteration. Adding the
inhibitors of JAK/Stat3 signaling or neutralizing antibodies of IL-6 or leptin
increased the susceptibility of CRPC cells to NK cell action. CONCLUSIONS:
Blocking the adipocyte effect by inhibiting the IL-6/leptin-JAK/Stat3 signaling
axis may enhance NK cell mediated immunity to CRPC cells and this strategy may
help to develop future therapeutics to treat obese PCa patients.
PMID- 29330930
TI - Gender-specific risk factors for androgenetic alopecia in the Korean general
population: Associations with medical comorbidities and general health behaviors.
AB - BACKGROUND: The relationships between androgenetic alopecia (AGA) and various
factors related to metabolic syndrome have been demonstrated in previous studies.
However, it remains unclear because of inconsistent results. We investigated the
associations between AGA and various risk factors related to metabolic syndrome
according to gender. METHODS: We conducted a population-based cross-sectional
survey of 2028 Koreans (1050 men, 978 women). The basic and specific (BASP)
classification was used for diagnosis of AGA. We collected information on risk
factors though questionnaires and medical records. RESULTS: AGA was significantly
associated with age, family history of AGA, hypertension, diabetes mellitus, and
waist circumference in both genders. Female subjects with AGA were more likely to
have cerebrovascular disease, dyslipidemia, and obesity; however, these
associations were not observed in the male subjects. When multiple regression
analysis was applied, there was a significant relationship between hypertension
and AGA in male subjects. However, there was no statistically significant
association in female subjects. CONCLUSION: The different results according to
gender might arise from different mechanisms of AGA. There was a significant
relationship between hypertension and AGA in male subjects. Evaluation of blood
pressure in male patients with AGA might facilitate interventions for
hypertension.
PMID- 29330931
TI - Teaching & Learning Tips 4: Motivation and emotion in learning.
AB - Challenge: Trainees' motivational and emotional states can influence their
learning and career decisions, but historically these "affective" learning
factors have received little attention in medical education. In this "Tips"
piece, we outline strategies to positively influence trainees' intrinsic
motivation and emotion toward their training to ultimately enhance their overall
learning experience.
PMID- 29330932
TI - Influences for gender disparity in dermatology in North America.
AB - BACKGROUND: Despite constituting half the population, women represent a minority
of active physicians and hold a small proportion of faculty leadership positions
in North America. However, dermatology is one of the few specialties where women
comprise a substantial portion of the workforce. This study explores extent and
contributors to gender disparity in academic dermatology faculty positions,
leadership, and research. METHODS: We collected data on academic faculty
including leadership from the websites of accredited U.S. and Canadian
dermatology faculties. We used PubMed and SCOPUS to collect faculty research
information including h-index, number of publications, citations, and years of
active research. RESULTS: Although women constitute almost half of all
dermatologists in the U.S. and Canada (47.9%), only one-fourth (26.1%) of all
faculty heads are women. Furthermore, the proportion of women in higher faculty
ranks (Assistant Professor, Associate Professors, and Professors) is much lower
than males. Female dermatologists also have fewer publications, citations, and
years of active research. Interestingly, having a female in a leadership position
is associated with a higher proportion of female dermatologists in the faculty.
CONCLUSIONS: Gender disparity exists in academic dermatology, and the current
academics fail to account for the enormous social challenges that women face,
which may put them at a disadvantage to career advancement. Among other factors,
better representation of female leadership may encourage and inspire women
joining academic faculties in the future.
PMID- 29330933
TI - To avoid a misleading genetic diagnosis of epidermolysis bullosa.
PMID- 29330934
TI - Melatonin inhibits the proliferation of breast cancer cells induced by bisphenol
A via targeting estrogen receptor-related pathways.
AB - BACKGROUND: Background: Bisphenol A (BPA) is an estrogen-like chemical widely
contained in daily supplies. There is evidence that environmental exposure to BPA
could contribute to the development of hormone-related cancers. As is reported in
numerous studies, melatonin, an endogenous hormone secreted by the pineal gland,
could markedly inhibit estrogen-induced proliferation of breast cancer (BC)
cells. In this study, we intended to reveal the effects of melatonin on BPA
induced proliferation of estrogen receptor-positive BC cells. METHODS: Methods:
We used methyl thiazolyl tetrazolium, luciferase reporter gene and western
blotting assays to testify the effect of melatonin on BPA-mediated proliferation
of MCF-7 and T47D cells. RESULTS: Methyl thiazolyl tetrazolium and colony
formation assays showed that melatonin could significantly abolish BPA-elevated
cell proliferation. Meanwhile, BPA-upregulated phosphorylation of ERK and AKT was
decreased by melatonin treatment. Mechanistically, we found that BPA was capable
of upregulating the protein levels of steroid receptor coactivators (SRC-1, SRC
3), as well as promoting the estrogen response element activity. However, the
addition of melatonin could remarkably block the elevation of steroid receptor
coactivators expression and estrogen response element activity triggered by BPA.
CONCLUSION: Conclusions: Therefore, these results demonstrated that melatonin
could abrogate BPA-induced proliferation of BC cells. Therapeutically, melatonin
could be regarded as a potential medication for BPA-associated BC.
PMID- 29330935
TI - Takotsubo cardiomyopathy in a young adult with transplanted heart: what happened
to denervation?
AB - This manuscript describes the first report of takotsubo cardiomyopathy in a young
heart transplant recipient following angry debate. Our patient is a 21-year-old
woman with cardiac transplant performed owing to right ventricular failure in
congenital heart disease. Positive echocardiography with typical asymmetry of
regional function, positive enzymes, and negative biopsy and angiography met the
criteria for the diagnosis of takotsubo cardiomyopathy. Patient was discharged
after 1 week in good clinical conditions and fully recovered cardiac function.
The development of takotsubo cardiomyopathy in transplanted heart suggests that
re-innervation occurs, thus representing a target for catecholamine-induced
cardiac dysfunction.
PMID- 29330936
TI - Give me a sample of air and I will tell which species are found from your region:
Molecular identification of fungi from airborne spore samples.
AB - Fungi are a megadiverse group of organisms, they play major roles in ecosystem
functioning and are important for human health, food production and nature
conservation. Our knowledge on fungal diversity and fungal ecology is however
still very limited, in part because surveying and identifying fungi is time
demanding and requires expert knowledge. We present a method that allows anyone
to generate a list of fungal species likely to occur in a region of interest,
with minimal effort and without requiring taxonomical expertise. The method
consists of using a cyclone sampler to acquire fungal spores directly from the
air to an Eppendorf tube, and applying DNA barcoding with probabilistic species
identification to generate a list of species from the sample. We tested the
feasibility of the method by acquiring replicate air samples from different
geographical regions within Finland. Our results show that air sampling is
adequate for regional-level surveys, with samples collected >100 km apart varying
but samples collected <10 km apart not varying in their species composition. The
data show marked phenology, and thus obtaining a representative species list
requires aerial sampling that covers the entire fruiting season. In sum, aerial
sampling combined with probabilistic molecular species identification offers a
highly effective method for generating a species list of air-dispersing fungi.
The method presented here has the potential to revolutionize fungal surveys, as
it provides a highly cost-efficient way to include fungi as a part of large-scale
biodiversity assessments and monitoring programs.
PMID- 29330937
TI - First-time detection of porcine reproductive and respiratory syndrome virus
(PRRSV) infection in Uruguay.
AB - Within the last two decades, several high-impact viruses have emerged in the
global swine population, including porcine reproductive and respiratory syndrome
virus (PRRSV). In Uruguay, the more recent serological survey for PRRSV and other
notifiable diseases such as Aujeszky's disease virus (ADV) and classical swine
fever virus (CSFV) dated from year 2000. The main purpose of this study was to
update our information on the infection status of PRRSV, ADV and CSFV in
Uruguayan pig herds, in order to keep informed about the epidemiological
situation of these notifiable infections in the country. For serological testing,
a total of 524 swine serum samples collected during the period 2014-2016 were
assayed by commercial ELISAs. Our results revealed the (unexpected) presence of
PRRSV antibodies in Uruguayan domestic swine herds and confirmed the absence of
ADV and CSFV antibodies in all of the assessed samples. Following such initial
finding, PRRSV antibodies were further investigated in 23 retrospective samples
collected during 2010-2014. Thirteen of these 23 samples resulted seropositive.
Subsequently, a molecular detection approach in frozen serum samples was
implemented to confirm PRRSV infection, and viral RNA was identified by reverse
transcription-nested polymerase chain reaction (RT-nPCR). Fourteen of 86
evaluated 2014-2016 samples resulted positive for viral RNA, while molecular
analysis of four retrospective samples also revealed the presence of PRRSV type
2. Viral isolation of selected samples was carried out in porcine alveolar
macrophages (PAM) and MARC 145 simian kidney cells, and the virus identity was
confirmed by cytopathic effect (CPE) and immunofluorescence assay (IFA) using
specific monoclonal antibodies for PRRSV nucleocapsid. Data reported here
evidence for the first time the circulation of PRRSV type 2 in Uruguay, and
retrospective serology results suggest that the virus has been infecting pigs in
this country at least since 2011.
PMID- 29330938
TI - Predictive value of neutrophil to lymphocyte ratio in long-term outcomes of left
main and/or three-vessel disease in patients with acute myocardial infarction.
AB - OBJECTIVES: We sought to evaluate the independent predictive value of left main
disease (LMD) and/or three-vessel disease (LMD/3VD) in acute myocardial
infarction (AMI) patients. BACKGROUND: Patients with acute coronary syndrome
resulting from LMD and/or three-vessel disease (LMD/3VD) are at the highest risk
of adverse cardiovascular events. Neutrophil to lymphocyte ratio (NLR) has been
proposed as a marker of cardiovascular risk, but the prognostic value of NLR in
patients with LMD/3VD who underwent percutaneous coronary intervention (PCI) is
not clearly defined. METHODS: Patients (n = 806) admitted with LMD/3VD who
underwent PCI between January 2013 and December 2013 were followed up for 2
years. Admission NLR was divided into two sub-groups based on an optimal cut off
value predicting 2-year all-cause mortality. The primary end point was all-cause
death. The secondary end point was long-term major adverse cardiovascular and
cerebrovascular events (MACCE). RESULTS: During follow-up, the high NLR group was
associated with a significantly higher rate of long-term all-cause mortality (6.7
vs. 0.9%, P < .001), and MACCE (24.7 vs. 15.8%, P = .002) compared to the low NLR
group. In multivariate analysis, after adjusting for risk factors, NLR >= 3.39
was determined to be an independent predictor of 2-year all-cause mortality
(hazard ratio[HR] 3.08, 95% confidence interval [CI] 1.06 to 8.97, P = .039) and
MACCE (hazard ratio 1.44, 95% CI 1.01 to 2.05, P = .046) for LMD/3VD.
CONCLUSIONS: The admission NLR as relatively inexpensive marker of inflammation
may aid in the risk stratification and prognosis of patients diagnosed with
LMD/3VD.
PMID- 29330939
TI - Corrigendum.
PMID- 29330940
TI - Extracorporeal shockwave therapy for treatment of keloid scars.
AB - The purpose of this investigation was to study the effectiveness of
extracorporeal shockwave therapy (ESWT) for the treatment of keloid scars, and
compared the results with intralesional steroid injection. Thirty-nine patients
were randomly divided into 22 in ESWT group and 17 in steroid group. The ESWT
group received 3 ESWT treatments in 6 weeks. The steroid group received three
intra-lesional triamcinolone injections in 6 weeks. The evaluations included
gross morphology, functional outcome, local blood flow perfusion, biopsy for
histopathological examination, and immunohistochemical analysis. Both groups
showed significant improvements in appearance with less discoloration, flattening
and softer consistency, and more elasticity of the lesions. There is a
significant reduction in keloid height after treatment in both groups, and
significant differences are noticed between two groups after treatment. The
volume of keloid was decreased after treatment but there is no statistically
significant difference between two groups. Both groups showed comparable
functional scores, POSAS patient, and observer scales. The blood flow perfusion
rates were statistically not significant between two groups before and after
treatments. Histopathological findings revealed no significant difference in cell
count, cell activity, and cell concentration between two groups. After ESWT, the
significant decreases in collagen type I, type III, and Masson Trichrome stain
were observed as compared with steroid group. However, very little changes were
noticed in angiogenesis, inflammatory cytokines, proliferating and regeneration,
and apoptosis, with no statistical significance noticed between two groups before
and after treatment. This study revealed that ESWT showed comparable functional
outcome and POSAS patient and observer scales as compared with steroid injection
for keloid scars. Treatment of keloid scars with ESWT resulted in significant
decreases in collagen fibers and increases in MMP-13 enzyme.
PMID- 29330941
TI - Hydrophobic and hydrophilic effects on water structuring and adhesion in denture
adhesives.
AB - Denture adhesives are designed to be moisture-sensitive through the inclusion of
a blend of polymer salts with varying degrees of water-sensitivity. This enables
the adhesive to mix with saliva in vivo and activate its high tack, through the
formation of a mucilaginous layer. We report for the first time, the use of
differential scanning calorimetry to study a series of hydrophobic and
hydrophilic polymeric systems in order to correlate water-structuring behavior
with adhesion strength. Adhesive bonding of the more hydrophobic variants was
higher than that of a commercial-based control and a more hydrophilic polymer
system in both lap shear and tensile configurations. Water-binding data suggested
that increasing the hydrophobicity of the maleic acid copolymer substituents led
to decreased levels of freezing water. In comparison, increasing the hydrophilic
nature of the polymer backbone gave higher levels of freezing water within the
hydrated samples. The results of this study emphasize the importance of varying
the levels of hydrophobic and hydrophilic components within denture adhesive
formulations, alongside the types of water present within the adhesive systems.
This phenomenon has shown the potential to fine-tune the adhesive properties and
failure mode against poly(methyl methacrylate), surfaces. (c) 2018 Wiley
Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1355-1362, 2018.
PMID- 29330942
TI - Skeletal development in the heterocercal caudal fin of spotted gar (lepisosteus
oculatus) and other lepisosteiformes.
AB - BACKGROUND: The caudal fin of actinopterygians experienced substantial
morphological changes during evolution. In basal actinopterygians, the caudal fin
skeleton supports an asymmetrical heterocercal caudal fin, while most teleosts
have a symmetrical homocercal caudal fin. The transition from the ancestral
heterocercal form to the derived homocercal caudal fin remains poorly understood.
Few developmental studies provide an understanding of derived and ancestral
characters among basal actinopterygians. To fill this gap, we examined the
development of the caudal fin of spotted gar Lepisosteus oculatus, one of only
eight living species of Holostei, the sister group to the teleosts. RESULTS: Our
observations of animals from fertilization to more than a year old provide the
most detailed description of the development of caudal fin skeletal elements in
any Holostean species. We observed two different types of distal caudal radials
replacing two transient plates of connective tissue, identifying two hypaxial
ensembles separated by a space between hypurals 2 and 3. These features have not
been described in any gar species, but can be observed in other gar species, and
thus represent anatomical structures common to lepisosteiformes. CONCLUSIONS: The
present work highlights the power and importance of ontogenic studies and
provides bases for future evolutionary and morphological investigations on
actinopterygians fins. Developmental Dynamics 247:724-740, 2018. (c) 2018 Wiley
Periodicals, Inc.
PMID- 29330943
TI - Epigenetic markers in circulating cell-free DNA as prognostic markers for
survival of castration-resistant prostate cancer patients.
AB - BACKGROUND: Noninvasive biomarkers to guide personalized treatment for castration
resistant prostate cancer (CRPC) are needed. In this study, we analyzed
hypermethylation patterns of two genes (GSTP1 and APC) in plasma cell-free DNA
(cfDNA) of CRPC patients. The aim of this study was to analyze the cfDNA
concentrations and levels of the epigenetic markers and to assess the value of
these biomarkers for prognosis. METHODS: In this prospective study, patients were
included before starting new treatment after developing CRPC. The blood samples
were collected prior to start of the treatment and at three time points
thereafter. cfDNA was extracted from 1.5 mL of plasma and before performing a
methylation-specific PCR, bisulfate modification was carried out. RESULTS: The
median levels of cfDNA, GSTP1, and APC copies in the baseline samples of CRPC
patients (n = 47) were higher than in controls (n = 30). In the survival
analysis, the group with baseline marker levels below median had significant less
PCa-related deaths (P-values <0.02) and did not reach the median survival point.
The survival distributions for the groups were statistically significant for the
cfDNA concentration, GSTP1 and APC copies, as well as PSA combined with GSTP1 +
APC (P-values <0.03). Furthermore, there were strong positive correlations
between PSA and marker response after starting treatment (P-values <0.04).
CONCLUSIONS: In conclusion, this study showed the kinetics of methylated cfDNA
(GSTP1 and APC) in plasma of CRPC patients after starting treatment. Furthermore,
the value of the markers before treatment is prognostic for overall survival.
These results are promising for developing a test to guide treatment-decision
making for CRPC patients.
PMID- 29330944
TI - Improvement of islet function and survival by integration of perfluorodecalin
into microcapsules in vivo and in vitro.
AB - Hypoxic injury of islets is a major obstacle for encapsulated islet
transplantation into the peritoneal cavity. To improve oxygen delivery to
encapsulated islets, we integrated 20% of the oxygen carrier material,
perfluorodecalin (PFD), in alginate capsules mixed with islets (PFD-alginate).
Integration of PFD clearly improved islet viability and decreased reactive oxygen
species production compared to islets encapsulated with alginate only (alginate)
and naked islets exposed to hypoxia in vitro. In PFD-alginate capsules, HIF
1alpha expression was minimal, and insulin expression was well maintained.
Furthermore, the best islet function represented by glucose-stimulated insulin
secretion was observed for the PFD-alginate capsules in hypoxic condition. For
the in vivo study, the same number of naked islets and encapsulated islets
(alginate and PFD-alginate) was transplanted into streptozotocin-induced diabetic
mice. Nonfasting blood glucose levels and the area under the curve for glucose
based on intraperitoneal glucose tolerance tests in the PFD-alginate group were
lower than in the alginate group. The harvested islets stained positive for
insulin in all groups, but the ratio of dead cell area was 4 times higher in the
alginate group than in the PFD-alginate group. In conclusion, integration of PFD
in alginate microcapsules improved islet function and survival by minimizing the
hypoxic damage of islets after intraperitoneal transplantation.
PMID- 29330945
TI - Cyclosporine A induces endothelin-converting enzyme-1: Studies in vivo and in
vitro.
AB - AIM: Cyclosporine A (CsA) induces renal vasoconstriction and hypoxia and enhances
the expression of endothelin-1 (ET-1) pro-hormone (pre-pro-ET-1), plausibly
leading to a feed-forward loop of renal vasoconstriction, hypoxia and enhanced
synthesis of the potent vasoconstrictor ET-1. Endothelin-converting enzyme (ECE)
1 cleaves big endothelin to generate endothelin (ET)-1 and is upregulated by
hypoxia via hypoxia-inducible factor (HIF). We hypothesized that in addition to
the direct induction of ET-1 synthesis, CsA might also intensify renal ECE-1
expression, thus contributing to enhanced ET-1 synthesis following CsA. METHODS:
CsA was administered to Sprague Dawley rats (120 mg/kg/SC) for 4 days, and renal
HIF and ECE-1 expression were assessed with Western blots and immunostaining.
Human umbilical vein endothelial cells (HUVEC) and proximal tubular cell line (HK
2) were subjected to CsA, and ECE-1 induction was evaluated using real-time mRNA
PCR and Western blots. RESULTS: Cyclosporine A intensified renal parenchymal ECE
1 expression in the rat kidney, particularly in distal nephron segments, along
with renal hypoxia (detected by pimonidazole adducts) and HIF expression, in line
with our recent observations showing episodic hypoxia in mice subjected to CsA.
Furthermore, in cultured normoxic HUVEC and HK-2 cells, CsA dose-dependently
induced both pre-pro-ET-1 and ECE-1 mRNA and protein expression, with enhanced ET
1 generation. CONCLUSION: CsA induces ECE-1 via both hypoxic and non-hypoxic
pathways. ECE-1 may contribute to increased renal ET-1 generation following CsA,
participating in a feed-forward loop of renal parenchymal hypoxia and ET
synthesis.
PMID- 29330946
TI - Skull Size and Biomechanics are Good Estimators of In Vivo Bite Force in Murid
Rodents.
AB - Rodentia is a species-rich group with diversified modes of life and diets.
Although rodent skull morphology has been the focus of a voluminous literature,
the functional significance of its variations has yet to be explored in live
animals. Myomorphous rodents, including murids, have been suggested to represent
"high-performance generalists." We measured in vivo bite force in 14 species of
wild and lab-reared murid rodents of various sizes and diets to investigate
potential morphofunctional differences between them. We dissected their skulls
and computed a biomechanical model to estimate bite force. We first tested if our
model allowed good estimation of in vivo data. Then, using morphological, in vivo
and estimated bite force data in a phylogenetic context, we aimed to find the
drivers of bite force differences among species. Estimated and in vivo bite
forces were strongly correlated, which indicates that (a) biomechanical models
allow a good estimation of real performance, and that (b) size and muscular
changes (increased mass, fiber length, and PCSA) are the main drivers of bite
performance differences. Myomorphous rodents, therefore, may have evolved high
bite force through a combination of changes in size and musculature, which gave
them a great versatility in their ability to process food. We found mixed results
at the intraspecific level, with only some species displaying a good fit between
estimated and in vivo measurements. We suggest that limited variation in size and
muscular organization, and increased behavioral variation might decrease the
precision of bite force estimates within species. Anat Rec, 301:256-266, 2018.
(c) 2018 Wiley Periodicals, Inc.
PMID- 29330947
TI - Dietary Correlates of Primate Masticatory Muscle Fiber Architecture.
AB - Analyses of masticatory muscle architecture-specifically fascicle length (FL; a
correlate of muscle stretch and contraction speed) and physiological cross
sectional area (PCSA; a correlate of force)-reveal soft-tissue dietary
adaptations. For instance, consumers of large, soft foods are expected to have
relatively long FL, while consumers of obdurate foods are expected to have
relatively high PCSA. Unfortunately, only a few studies have analyzed these
variables across large primate samples-an order of particular interest because it
is our own. Previous studies found that, in strepsirrhines, force variables (PCSA
and muscle masses; MM) scale with isometry or slight positive allometry, while
the body size corrected FL residuals correlate with food sizes. However, a study
of platyrrhines using different methods (in which the authors physically cut
muscles between fascicles) found very different trends: negative allometry for
both the stretch and force variables. Here, we apply the methods used in the
strepsirrhine study (chemical dissection of fascicles to ensure full length
measurements) to reevaluate these trends in platyrrhines and extend this research
to include catarrhines. Our results conform to the previous strepsirrhine trends:
there is no evidence of negative allometry in platyrrhines. Rather, in primates
broadly and catarrhines specifically, MM and PCSA scale with isometry or positive
allometry. When examining size-adjusted variables, it is clear that fascicle
lengths (especially those of the temporalis muscle) correlate with diet: species
that consume soft, larger, foods have longer masticatory fiber lengths which
would allow them to open their jaws to wider gape angles. Anat Rec, 301:311-324,
2018. (c) 2018 Wiley Periodicals, Inc.
PMID- 29330948
TI - Inferring the Diets of Extinct Giant Lemurs from Osteological Correlates of
Muscle Dimensions.
AB - The jaw adductor muscles of extinct mammals are often reconstructed to elucidate
paleoecological relationships and to make broad comparisons among taxa. Muscle
lever arms, bite load arms, muscle dimensions, and gape are often also
reconstructed to better understand feeding. Several different approaches to these
and related goals are discussed here. A protocol for reconstructing muscle
dimensions and bite force using biomechanically informative skull measurements
and osteological proxies of muscle dimensions is described and applied to a case
study of subfossil Malagasy lemurs. The results of this case study show that most
subfossil lemurs emphasized the masseter and medial pterygoid muscles over the
temporalis. This supports the inference that these extinct lemurs depended
heavily on tough food like leaves. Exceptions include signals of hard-object
feeding in Archaeolemur that vary between A. majori and A. edwardsi.
Reconstructions of soft-tissue and function are important for understanding past
ecological relationships. Even those based on well-supported osteological proxies
from extant analogues have limitations for making precise inferences. Anat Rec,
301:343-362, 2018. (c) 2018 Wiley Periodicals, Inc.
PMID- 29330949
TI - Functional Morphology of Mimetic Musculature in Primates: How Social Variables
and Body Size Stack up to Phylogeny.
AB - Mammalian skeletal muscle is influenced by the functional demands placed upon it.
Functional morphology of facial expression musculature, or mimetic musculature,
is largely unknown. Recently, primate mimetic musculature has been shown to
respond to demands associated with social factors. Body size has also been
demonstrated to affect many aspects of primate functional morphology and
evolutionary morphology. The present study was designed to further examine the
role of social variables and body size in influencing the morphology of primate
mimetic musculature using a broad phylogenetic range of primates, primates with
varying body sizes, and those that exploit differing time of day activity cycles
and social group sizes. Gross data on mimetic musculature morphology were
gathered from tarsiers (Tarsius bancanus), slender lorises (Loris tardigradus),
ring-tailed lemurs (Lemur catta), crowned lemurs (Eulemur coronatus), black
lemurs (E. macaco), owl monkeys (Aotus trivirgatus), and howler monkeys (Alouatta
caraya) and compared to previous results from chimpanzees (Pan troglodytes),
gibbons and siamangs (hylobatids), rhesus macaques (Macaca mulatta), Sulawesi
macaques (M. nigra), common marmosets (Callithrix jacchus), and greater
bushbabies (Otolemur spp.). Mimetic muscle presence/absence was observed and
recorded. Results revealed that phylogenetic position determines the overall
mimetic muscle groundplan, with anthropoids having a high number of muscles in
the superciliary and midface regions, strepsirrhines having a high number of
muscles in the external ear region, and tarsiers displaying an intermediate
condition. Within these broad taxonomic categories body size had an effect on
mimetic musculature, while time of day activity and social group size had smaller
effects. Anat Rec, 301:202-215, 2018. (c) 2018 Wiley Periodicals, Inc.
PMID- 29330950
TI - Comparative Anatomy of Bat Jaw Musculature via Diffusible Iodine-Based Contrast
Enhanced Computed Tomography.
AB - Noctilionoid bats exhibit an extraordinary array of cranial specializations that
match diverse diets, including variation in jaw musculature physiological cross
sectional areas (PCSA), lever arms, and relative contribution to bite force.
Although previous research in this group has linked variation in skull shape and
muscle mechanics to biting performance, there are still important gaps about the
anatomical underpinnings of noctilionoid dietary adaptations, including the
degree of compartmentalization of the jaw musculature, and whether and how muscle
attachment sites have evolved across noctilionoid species that specialize on
derived diets. Here, we paired dissections with Diffusible Iodine-based Contrast
Enhanced Computed Tomography (diceCT) scanning in a comparative anatomical study
of the jaw musculature of 12 noctilionoid species that span all diets found
within the clade. We evaluated changes in jaw muscle attachments across species,
identified differences in muscle compartments, examined scaling relationships,
and compared the power of diceCT and dissections to generate morphological data.
We found that diceCT enables more detailed investigation of muscle compartments
and generates greater PCSA values, but these are strongly correlated with
estimates from dissections. Jaw muscle origin and insertion sites are relatively
conserved across noctilionoids when compared to other species-rich and
ecologically-diverse mammalian groups. However, we found interspecific
differences in the degree of separation of the m. masseter, and in the scaling
relationships of different jaw muscles with body mass, both of which might be
associated with diet and feeding behavior specialization. Our study highlights an
unexplored diversity in the compartmentalization and fiber architecture of bat
jaw muscles. Anat Rec, 301:267-278, 2018. (c) 2018 Wiley Periodicals, Inc.
PMID- 29330952
TI - Jaw-Muscle Fiber Architecture and Leverage in the Hard-Object Feeding Sooty
Mangabey are not Structured to Facilitate Relatively Large Bite Forces Compared
to Other Papionins.
AB - Numerous studies have sought to link craniofacial morphology with behavioral
ecology in primates. Extant hard-object feeders have been of particular interest
because of their potential to inform our understanding about the diets of early
fossil hominins. Sooty mangabeys (Cercocebus atys) are hard-object feeders that
frequently generate what have been described as audibly powerful bites at wide
jaw gapes to process materially stiff and hard seeds. We address the hypothesis
that sooty mangabeys have features of the masticatory apparatus that facilitate
this feeding behavior by comparing fiber architecture and leverage of the
masseter and temporalis muscles between sooty mangabeys and three papionin
primates that do not specialize on hard objects. Contrary to predictions, sooty
mangabeys do not have relatively larger muscle physiologic cross-sectional areas
or weights compared to other papionins, nor do they consistently display improved
leverage. In this regard, sooty mangabeys differ in their morphology from other
hard-object feeders such as tufted capuchins. However, males of all four papionin
species converge on a shared pattern of relatively longer anterior superficial
masseter fibers compared with female conspecifics, suggesting that males are
likely prioritizing muscle stretch to improve gape performance as part of a
behavioral repertoire that includes agonistic social interactions and intense
male-male competition. These findings strengthen support for the hypothesis that
gape display behaviors can exert a strong selective influence throughout the
musculoskeletal masticatory apparatus. Results also raise questions about the
morphological suitability of extant cercopithecines as models for interpreting
feeding behavior and diet in fossil hominins with limited jaw gape capacity. Anat
Rec, 301:325-342, 2018. (c) 2018 Wiley Periodicals, Inc.
PMID- 29330953
TI - Jaw-Dropping: Functional Variation in the Digastric Muscle in Bats.
AB - Diet and feeding behavior in mammals is strongly linked to the morphology of
their feeding apparatus. Cranio-muscular morphology determines how wide,
forcefully, and quickly the jaw can be opened or closed, which limits the size
and material properties of the foods that a mammal can eat. Most studies of
feeding performance in mammals have focused on skull form and jaw muscles
involved in generating bite force, but few explore how jaw abduction is related
to feeding performance. In this study, we explored how the morphology of the
digastric muscle, the primary jaw abducting muscle in mammals, and its jaw lever
mechanics are related to diet in morphologically diverse noctilionoid bats.
Results showed that insectivorous bats have strong digastric muscles associated
with proportionally long jaws, which suggests these species can open their jaws
quickly and powerfully during prey capture and chewing. Short snouted frugivorous
bats exhibit traits that would enable them to open their jaws proportionally
wider to accommodate the large fruits that they commonly feed on. Our results
support the hypothesis that digastric muscle and jaw morphology are correlated
with diet in bats, and that our results may also apply to other groups of
mammals. Anat Rec, 301:279-290, 2018. (c) 2018 Wiley Periodicals, Inc.
PMID- 29330954
TI - Why Muscles Look and Act the Way They Do: Uncovering the Nexus Among Form,
Function, Behavior, and Evolution.
PMID- 29330955
TI - Intrinsic Constraints on the Diversification of Neotropical Cichlid Adductor
Mandibulae Size.
AB - The diversification of functional traits may be constrained by intrinsic factors,
such as structural, mechanical, developmental, or physiological limitations. We
explored the biomechanical and constructional constraints on the size of the
major jaw closing muscles, the adductor mandibulae complex (AM), in a diverse
clade of freshwater fish - the Neotropical cichlids. Using phylogenetic
comparative methods, we contrasted patterns of size variation and diversification
rates of three AM divisions with variables describing head size and biomechanical
coefficients describing force and velocity transmission. We found that all three
AM muscles examined were impacted by constructional constraints, namely, (1) the
space available in the head (head length and width-all AMs), (2) competition with
the eye (AM1 and AM2), (3) competition for space among the three major AM
divisions (e.g., AM1 vs. AM3), and (4) potentially the shape of the lower jaw
(AM2). Only AM2 size was significantly associated with lower jaw biomechanical
coefficients, but opposite predictions based on force transmission (i.e., no
compensation for low mechanical advantage). Diversification rates of the mass of
the divisions of the AM were also not connected to the diversification rates of
their biomechanical coefficients. Previously suggested compensation in AM mass
for reduced force transmission among ram-feeding predators appears to be driven
by overall body plan changes (lengthening of the head in elongate bodies) and
only indirectly to biomechanical trade-offs. Strong constructional constraints on
AM size likely limit potentially functional morphospace occupation, and highlight
the highly integrated nature of ram-suction feeding functional adaptations in
Neotropical cichlids. Anat Rec, 301:216-226, 2018. (c) 2018 Wiley Periodicals,
Inc.
PMID- 29330956
TI - Craniomandibular Variation in Phalangeriform Marsupials: Functional Comparisons
with Primates.
AB - Phalangeriform marsupials have often been compared with primates because of
similarity in the range of external morphology, ecological niches, and body size
between the two radiations. We explore morphological convergence in the
masticatory anatomy of strepsirrhine primates and phalangeriforms, through
osteological measurements of the mandible and facial skeleton, and through
dissection of the masticatory musculature, presenting new data on the arrangement
and proportions of jaw adductors in phalangeriforms. Phalangeriforms and primates
have a large number of shape differences in mandibular morphology. Despite these
differences in shape on phylogenetic lines, dietary groups used to pool species
of phalangeriforms and strepsirrhines also differed from each other in a range of
shape variables. Notably, the striped possum (Dactylopsila), previously described
as convergent with the aye-aye (Daubentonia), shares a number of features of
mandibular shape with Daubentonia, and the exudate-feeding sugar-glider,
Petaurus, shares shape features with gummivorous strepsirrhines. Petaurus also
has long-fibered jaw adductors for its body mass, as would be expected for a
species with a requirement for large gape. Phalangeriform species on the
frugivore-folivore continuum were less clearly comparable to strepsirrhine
species with similar diets. There are a number of significant dietary contrasts
in osteological measurements, but in the masticatory muscles phalangeriforms did
not meet all expectations based on available dietary data, highlighting the
possible complexity of dietary adaptation in phalangeriform folivores. Anat Rec,
301:227-255, 2018. (c) 2018 Wiley Periodicals, Inc.
PMID- 29330951
TI - Dynamic Musculoskeletal Functional Morphology: Integrating diceCT and XROMM.
AB - The tradeoff between force and velocity in skeletal muscle is a fundamental
constraint on vertebrate musculoskeletal design (form:function relationships).
Understanding how and why different lineages address this biomechanical problem
is an important goal of vertebrate musculoskeletal functional morphology. Our
ability to answer questions about the different solutions to this tradeoff has
been significantly improved by recent advances in techniques for quantifying
musculoskeletal morphology and movement. Herein, we have three objectives: (1)
review the morphological and physiological parameters that affect muscle function
and how these parameters interact; (2) discuss the necessity of integrating
morphological and physiological lines of evidence to understand muscle function
and the new, high resolution imaging technologies that do so; and (3) present a
method that integrates high spatiotemporal resolution motion capture (XROMM,
including its corollary fluoromicrometry), high resolution soft tissue imaging
(diceCT), and electromyography to study musculoskeletal dynamics in vivo. The
method is demonstrated using a case study of in vivo primate hyolingual
biomechanics during chewing and swallowing. A sensitivity analysis demonstrates
that small deviations in reconstructed hyoid muscle attachment site location
introduce an average error of 13.2% to in vivo muscle kinematics. The observed
hyoid and muscle kinematics suggest that hyoid elevation is produced by multiple
muscles and that fascicle rotation and tendon strain decouple fascicle strain
from hyoid movement and whole muscle length. Lastly, we highlight current
limitations of these techniques, some of which will likely soon be overcome
through methodological improvements, and some of which are inherent. Anat Rec,
301:378-406, 2018. (c) 2018 Wiley Periodicals, Inc.
PMID- 29330957
TI - Behavioral Correlates of Cranial Muscle Functional Morphology.
AB - This issue of the Anatomical Record is the first of a two-volume set that focuses
on new investigations into behavioral correlates of muscle functional morphology.
Much of the research on functional morphology and adaptation to specific
functional niches focuses on the shapes of hard-tissues-bones and teeth.
Investigations into soft-tissue anatomy tend to be predominantly descriptive with
only brief allusion to ontogenetic or evolutionary origins of structures. When
muscles are included in analyses of functional systems, their function tends to
be oversimplified-usually considered a simple force vector connecting two
osteological points, with the force treated as a constant derived from some
simple calculation of muscle size. The goal of these special issues is to present
a series of studies that take a more elaborate look at how muscles can be viewed
from a functional perspective in studies searching for morphological correlates
of behavior. This first volume focuses on the behavioral correlates of cranial
muscles-starting with a paper about the mimetic musculature of primates and
ending with a series of papers on the masticatory muscles of many lineages of
vertebrates. The next issue of the Anatomical Record (March 2018) includes our
papers on the behavioral correlates of postcranial muscles. Taken together, we
hope you agree that this series presents valuable insights into these
form/function relationships using both traditional approaches+ and cutting-edge
techniques. Anat Rec, 301:197-201, 2018. (c) 2018 Wiley Periodicals, Inc.
PMID- 29330958
TI - Do Muscles Constrain Skull Shape Evolution in Strepsirrhines?
AB - Despite great interest and decades of research, the musculoskeletal relationships
of the masticatory system in primates are still not fully understood. However,
without a clear understanding of the interplay between muscles and bones it
remains difficult to understand the functional significance of morphological
traits of the skeleton. Here, we aim to study the impacts of the masticatory
muscles on the shape of the cranium and the mandible as well as their co
variation in strepsirrhine primates. To do so, we use 3D geometric morphometric
approaches to assess the shape of each bone of the skull of 20 species for which
muscle data are available in the literature. Impacts of the masticatory muscles
on the skull shape were assessed using non-phylogenetic regressions and
phylogenetic regressions whereas co-variations were assessed using two-blocks
partial least square (2B-PLS) and phylogenetic 2B-PLS. Our results show that
there is a phylogenetic signal for skull shape and masticatory muscles. They also
show that there is a significant impact of the masticatory muscles on cranial
shape but not as much as on the mandible. The co-variations are also stronger
between the masticatory muscles and cranial shape even when taking into account
phylogeny. Interestingly, the results of co-variation between the masticatory
muscles and mandibular shape show a more complex pattern in two different
directions to get strong muscles associated with mandibular shape: a folivore way
(with the bamboo lemurs and sifakas) and a hard-object eater one (with the aye
aye). Anat Rec, 301:291-310, 2018. (c) 2018 Wiley Periodicals, Inc.
PMID- 29330959
TI - Non-Destructive Determination of Muscle Architectural Variables Through the Use
of DiceCT.
AB - The fascicular architecture of skeletal muscle dictates functional parameters
such as force production and contractile velocity. Muscle microarchitecture is
typically determined by means of manual dissection, a technique that is
inherently destructive to specimens. Furthermore, fascicle lengths and pennation
angles are commonly assessed at only a limited number of sampling sites per
muscle. We present the results of a digital technique to non-destructively assess
muscle architectural variables for three jaw-adductor muscles within a specimen
of the cercopithecine primate Macaca fascicularis (crab-eating macaque). The
specimen is first subjected to a contrast-enhanced staining protocol to increase
the density of internal soft tissues. High-resolution uCT scans are then
collected and segmented to isolate individual muscles. A textural orientation
algorithm is then applied to each muscle volume to reconstruct constituent muscle
fascicles in three dimensions. Using this technique, we report muscle volume,
fascicle length, angle of pennation, and physiological cross-sectional area
(PCSA) for each muscle. These data are compared to results collected using
traditional dissection of the contralateral muscles. Reconstructions of muscle
volume and pennation angle closely correspond to the dissection results. The
degree of similarity between measurements of fascicle length and PCSA varies
between muscles, with temporalis demonstrating the greatest disparity between
techniques; likely reflecting the complex geometry and fascicular arrangement of
this muscle. The described technique samples a much larger number of fascicles
than had previously been possible and non-destructively investigates the internal
architecture of preserved specimens. We conclude that this approach demonstrates
great potential for quantifying muscle internal architecture. Anat Rec, 301:363
377, 2018. (c) 2018 Wiley Periodicals, Inc.
PMID- 29330960
TI - The Anatomical Record Flexes Its Muscle With a Special Issue Examining Behavioral
Adaptations in Muscle Functional Morphology.
PMID- 29330961
TI - Clinical value of 4-hour delayed gadolinium-Enhanced 3D FLAIR MR Images in Acute
Vestibular Neuritis.
AB - OBJECTIVE: To investigate the clinical significance of 4-hour delayed-enhanced
3.0 Tesla three-dimensional (3D) fluid-attenuated inversion recovery (FLAIR)
magnetic resonance (MR) imaging in acute vestibular neuritis. STUDY DESIGN: A
prospective observational study. METHODS: Twenty-nine vestibular neuritis
patients were enrolled between January 2017 and June 2017. Vestibular function
tests, comprising the caloric and video head impulse tests and vestibular-evoked
myogenic potential measurements, were performed. Precontrast, 10-minute, and 4
hour delayed-enhanced 3D-FLAIR MR images using double-dose IV gadolinium were
obtained. After laterality and extent of inner ear enhancement were defined, the
patients were divided into groups based on the patterns of enhancement, and
clinical parameters were analyzed according to the groups. RESULTS: Twenty
patients (20 of 29, 69.0%) had obviously asymmetric enhancement of the affected
inner ear structures on 4-hour delayed images, whereas only three patients
(10.3%) had marked enhancement on 10-minute delayed images. The duration of
spontaneous nystagmus (DurSN) was significantly longer in the patients with
enhancement, especially with enhancement of the whole inner ear, including the
vestibule and semicircular canals (P < 0.033). Spontaneous nystagmus resolved
within 12 days in patients without laterality of enhancement, and within 16 days
in ipsilesional enhancement confined to the inner auditory canal and fundus.
Other results of vestibular function tests did not reveal any significant
associations with MR enhancement. CONCLUSIONS: Contrast enhancement of the
vestibular nerve and inner ear structures can be identified on 4-hour delayed
enhanced 3T 3D-FLAIR MR images in acute vestibular neuritis. The extent of inner
ear enhancement may be associated with the DurSN. LEVEL OF EVIDENCE: 4.
Laryngoscope, 1946-1951, 2018.
PMID- 29330962
TI - Skin Conformal Polymer Electrodes for Clinical ECG and EEG Recordings.
AB - Preparation-free and skin compliant biopotential electrodes with high recording
quality enable wearables for future healthcare and the Internet of Humans. Here,
super-soft and self-adhesive electrodes are presented for use on dry and hairy
skin without skin preparation or attachment pressure. The electrodes show a skin
contact impedance of 50 kOmega cm2 at 10 Hz that is comparable to clinical
standard gel electrodes and lower than existing dry electrodes. Microstructured
electrodes inspired by grasshopper feet adhere repeatedly to the skin with a
force of up to 0.1 N cm-2 without further attachment even during strong movement
or deformation of the skin. Skin compliance and adhesive properties of the
electrodes result in reduction of noise and motion artifacts superior to other
dry electrodes reaching the performance of commercial gel electrodes. The signal
quality is demonstrated by recording a high-fidelity electrocardiograms of a
swimmer in water. Furthermore, an electrode with soft macropillars is used to
detect alpha activity in the electroencephalograms from the back of the head
through dense hair. Compared to gel electrodes, the soft biopotential electrodes
are nearly imperceptible to the wearer and cause no skin irritations even after
hours of application. The electrodes presented here could combine unobtrusive and
long-term biopotential recordings with clinical-grade signal performance.
PMID- 29330963
TI - Metal-organic framework based in-syringe solid-phase extraction for the on-site
sampling of polycyclic aromatic hydrocarbons from environmental water samples.
AB - In-syringe solid-phase extraction is a promising sample pretreatment method for
the on-site sampling of water samples because of its outstanding advantages of
portability, simple operation, short extraction time, and low cost. In this work,
a novel in-syringe solid-phase extraction device using metal-organic frameworks
as the adsorbent was fabricated for the on-site sampling of polycyclic aromatic
hydrocarbons from environmental waters. Trace polycyclic aromatic hydrocarbons
were effectively extracted through the self-made device followed by gas
chromatography with mass spectrometry analysis. Owing to the excellent adsorption
performance of metal-organic frameworks, the analytes could be completely
adsorbed during one adsorption cycle, thus effectively shortening the extraction
time. Moreover, the adsorbed analytes could remain stable on the device for at
least 7 days, revealing the potential of the self-made device for on-site
sampling of degradable compounds in remote regions. The limit of detection ranged
from 0.20 to 1.9 ng/L under the optimum conditions. Satisfactory recoveries
varying from 84.4 to 104.5% and relative standard deviations below 9.7% were
obtained in real samples analysis. The results of this study promote the
application of metal-organic frameworks in sample preparation and demonstrate the
great potential of in-syringe solid-phase extraction for the on-site sampling of
trace contaminants in environmental waters.
PMID- 29330964
TI - Spectrum of bone marrow pathology and hematological abnormalities in
methylmalonic acidemia.
AB - Patients with isolated methylmalonic acidemia (MMA) may present with a wide range
of hematological complications including anemia, leukopenia, thrombocytopenia,
and pancytopenia. However, there are very limited data on the development of
hemophagocytosis or myelodysplasia in these patients. We report three patients
with isolated MUT related MMA who presented with severe refractory pancytopenia
during acute illness. Their bone marrow examination revealed a wide spectrum of
pathology varying from bone marrow hypoplasia, hemophagocytosis to myelodysplasia
with ring sideroblasts. We discuss their management and outcome. This report
emphasizes the need for bone marrow examination in these patients with refractory
or unexplained severe cytopenia, to confirm bone marrow pathology, and to rule
out other diseases with similar clinical presentation for a better clinical
outcome.
PMID- 29330965
TI - Intrahepatic bile duct primary cilia in biliary atresia.
AB - AIM: The etiopathogenesis of non-syndromic biliary atresia (BA) is obscure. The
primary aim was to investigate intrahepatic bile duct cilia (IHBC) in BA at
diagnosis and its correlation with clinical outcome. The secondary aim was to
analyze IHBC in routine paraffin-embedded liver biopsies using conventional
scanning electron microscopy (SEM). METHODS: Surgical liver biopsies taken at
diagnosis from 22 BA infants (age range, 39-116 days) and from eight children
with non-BA chronic cholestasis (age range, 162 days -16.8 years) were evaluated
for IHBC by immunofluorescence (IF) and SEM. A minimum 18-month follow-up after
surgery was available for all patients. RESULTS: By IF, cilia were present in 6/8
(75%) non-BA but only in 3/22 (14%) BA cases, and cilia were reduced or absent in
19/22 (86%) BA and 2/8 (25%) non-BA livers (P < 0.01). In BA, cilia presence was
found to be associated with clearance of jaundice at 6-month follow-up (P <
0.05). However, high overall survival rates with native liver, >90% at 12 months,
and >70% at 24 months post-surgery, were recorded regardless of cilia
presence/absence at diagnosis. Electron microscopy was able to detect bile ducts
and cilia in routine liver biopsies, revealing significant abnormalities in 100%
BA livers. CONCLUSIONS: The presence of IHBC in BA livers at the diagnosis was
associated with resolution of cholestasis, although was not predictive of short
term survival with native liver. Scanning electron microscopy represents a
powerful new tool to study routine liver biopsies in biliary disorders. Cilia
dysfunction in BA pathogenesis and/or disease progression warrants further
investigation.
PMID- 29330966
TI - Static hyperinflation is associated with ventilatory limitation and exercise
tolerance in adult cystic fibrosis.
AB - INTRODUCTION: Lung hyperinflation is a potential mechanism limiting exercise
tolerance. However, available data on the impact of static hyperinflation on
exercise performance in adult cystic fibrosis are lacking. Furthermore, the
relative contribution of both static and dynamic hyperinflation to exercise
performance is unknown. OBJECTIVES: The aim of this study was to determine the
impact of static hyperinflation on exercise tolerance and lung dynamics in adult
cystic fibrosis. METHODS: Clinical data of 107 adult patients with cystic
fibrosis, including pulmonary function, lung volumes and cardiopulmonary exercise
from the Toronto Cystic Fibrosis database, were collected and analyzed. Patients
were classified as having static hyperinflation with a residual volume to total
lung capacity (RV/TLC) ratio of 30% or greater. RESULTS: Patients with static
hyperinflation demonstrated a significant reduction in exercise performance [peak
oxygen uptake (% predicted) 70 +/- 17 vs 80 +/- 17; P = .006] and were more
likely to experience ventilatory limitation when exercising (Fisher's exact test
P < .001). Correlation analysis showed significant relationships between measures
of static hyperinflation [RV/TLC ratio (%)] and exercise performance [peak oxygen
uptake (% predicted); r = -.38, P < .001] and dynamic hyperinflation (r = -.35, P
< .001). Multiple linear regression showed that the contribution of static
hyperinflation to exercise performance [peak oxygen uptake (% predicted)] was
greater than that of airway obstruction (forced expiratory volume in 1 second).
CONCLUSION: Clinicians working with this patient group in a pulmonary
rehabilitation or health care setting may wish to consider using measures of
static hyperinflation as end points to determine program or treatment efficacy.
PMID- 29330968
TI - Correlation of dynamic contrast-enhanced MRI derived volume transfer constant
with histological angiogenic markers in high-grade gliomas.
AB - INTRODUCTION: To ascertain if the volume transfer constant (Ktrans ) derived from
T1 dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) correlates with
the immunohistological markers of angiogenesis in high-grade gliomas. METHODS:
Fifty-one image-guided biopsy specimens in 34 patients with newly presenting high
grade gliomas (grade III = 16; grade IV = 18) underwent preoperative imaging
(conventional imaging and T1 DCE-MRI). We correlated vascular endothelial growth
factor (VEGF) expression and the microvessel density (MVD) of MRI-guided biopsy
specimens with the corresponding DCE-derived Ktrans . Histological sections were
stained with VEGF and CD34, and examined under light microscopy. These
histological and molecular markers of angiogenesis were correlated with the
Ktrans of the region of interest corresponding to the biopsy specimen. RESULTS:
The Ktrans showed a significant positive correlation with VEGF expression (rho =
0.582, P = 0.001) but not with MVD stained with CD34 antibody (rho = 0.328, P =
0.072). CONCLUSION: The Ktrans derived from DCE-MRI can reflect the VEGF
expression of high-grade gliomas but not the MVD.
PMID- 29330967
TI - The impact of bisphenol S on bovine granulosa and theca cells.
AB - Bisphenol S (BPS) is an endocrine-disrupting chemical with multiple potential
mechanisms of action, including as an oestrogen receptor agonist. BPS is
increasingly used in plastics and thermal receipts as a substitute for bisphenol
A, which has been phased out due to concerns about human health implications. The
ability of BPS to alter female reproductive function in mammals has not been
widely studied, despite the importance of normal hormone signalling for female
reproduction. The aim of this study was to investigate how BPS (in a wide range
of doses, including very low doses) affects granulosa cell and theca cell steroid
hormone production and cell viability in the bovine. Granulosa cell oestradiol
production was stimulated when cells were exposed to 100 MUM BPS under basal
conditions, but there was no effect of BPS when cells were stimulated with
follicle-stimulating hormone (FSH). Additionally, there was no effect of BPS on
granulosa cell progesterone production or cell viability under basal or FSH
stimulated conditions. BPS did not affect theca cell androstenedione or
progesterone production, or theca cell viability under basal or luteinizing
hormone-stimulated conditions. This study suggests for the first time that BPS
may alter oestradiol production by bovine granulosa cells, albeit at a
concentration that is unlikely to be physiologically relevant. Further studies
are needed to determine the effects of BPS on the bovine oocyte and on other
functions of follicular cells.
PMID- 29330969
TI - Is salinity an obstacle for biological invasions?
AB - Invasions of freshwater habitats by marine and brackish species have become more
frequent in recent years with many of those species originating from the Ponto
Caspian region. Populations of Ponto-Caspian species have successfully
established in the North and Baltic Seas and their adjoining rivers, as well as
in the Great Lakes-St. Lawrence River region. To determine if Ponto-Caspian taxa
more readily acclimatize to and colonize diverse salinity habitats than taxa from
other regions, we conducted laboratory experiments on 22 populations of eight
gammarid species native to the Ponto-Caspian, Northern European and Great Lakes
St. Lawrence River regions. In addition, we conducted a literature search to
survey salinity ranges of these species worldwide. Finally, to explore
evolutionary relationships among examined species and their populations, we
sequenced the mitochondrial cytochrome c oxidase subunit I gene (COI) from
individuals used for our experiments. Our study revealed that all tested
populations tolerate wide ranges of salinity, however, different patterns arose
among species from different regions. Ponto-Caspian taxa showed lower mortality
in fresh water, while Northern European taxa showed lower mortality in fully
marine conditions. Genetic analyses showed evolutionary divergence among species
from different regions. Due to the geological history of the two regions, as well
as high tolerance of Ponto-Caspian species to fresh water, whereas Northern
European species are more tolerant of fully marine conditions, we suggest that
species originating from the Ponto-Caspian and Northern European regions may be
adapted to freshwater and marine environments, respectively. Consequently, the
perception that Ponto-Caspian species are more successful colonizers might be
biased by the fact that areas with highest introduction frequency of NIS (i.e.,
shipping ports) are environmentally variable habitats which often include
freshwater conditions that cannot be tolerated by euryhaline taxa of marine
origin.
PMID- 29330971
TI - Pakistan's March Towards Universal Health Coverage.
PMID- 29330970
TI - Gamma-glutamyl transferase activity as a predictive marker for severity of
obstructive sleep apnea syndrome and concomitant hypertension.
AB - BACKGROUND: Chronic intermittent hypia, inflammation and oxidative stress are
involved in resultant obstructive sleep apnea syndrome (OSAS), which may affect
numerous regulatory mechanisms that play a role in the regulation of blood
pressure. Gamma-glutamyl transferase (GGT) is a novel marker in the prediction of
cardiovascular risk. OBJECTIVE: The objective of this study was to investigate
the correlation of serum levels of GGT with hypertension and the degree of the
upper airway obstruction in subjects with OSAS. METHODS: A total of 270 subjects
that met the inclusion criteria were enrolled in the study. The subjects were
divided into four separate groups according to the apnea-hypopnea index (AHI)
scores as the control group (AHI < 5), mild OSAS group (AHI 5-15), moderate OSAS
group (AHI 16-30) and severe OSAS group (AHI >30). A further classification of
the OSAS subjects was made in two groups based on the presence of hypertension.
RESULTS: The study included 43 control individuals and 59 subjects with mild, 54
subjects with moderate and 114 subjects with severe OSAS. The serum levels of GGT
were found to be significantly correlated with OSAS severity (control group: 18
+/- 3.3, mild OSAS: 23.6 +/- 7.3, moderate OSAS: 26.4 +/- 7.5 and severe OSAS:
39.8 +/- 12). Serum levels of GGT were found to be significantly higher in OSAS
subjects with concomitant hypertension than in the group without associated
hypertension (P < .05). The results showed that the adjusted mean GGT under OSA
without hypertension (Madj = 28.76, SE = 0.71) was significantly lower than in
cases with OSA with hypertension (Madj = 42.79, SE = 1.19). CONCLUSION: The
present study indicated a strong correlation between high serum levels of GGT and
concomitant hypertension in subjects with obstructive sleep apnea. This biomarker
may be helpful in grading the severity of obstructive sleep apnea and correlated
with hypertension in this population.
PMID- 29330972
TI - Immunohistochemical Evaluation Of Oestrogen Receptors In Adenoid Cystic Carcinoma
Of Salivary Gland.
AB - Background: Oestrogen has a physiological role throughout the body including oral
cavity. The effects are mediated by binding to two receptors in nucleus alpha and
beta, which are ligand-activated transcription factors. The alpha receptors have
a prognostic significance in cancer of breast while in Adenoid cystic carcinoma
of salivary glands the results are inconsistent. This study was conducted to
determine the oestrogen receptor Alpha staining in adenoid cystic carcinoma of
salivary gland. Methods: Paraffin blocks of thirty cases of adenoid cystic
carcinoma of salivary gland were retrieved and evaluated through
immunohistochemistry by anti-oestrogen antibody clone 1D5.The intensity and
proportion of nuclear staining was scored using Allred scoring system. Results:
From total of thirty cases, 5 cases expressed as mild staining of oestrogen
receptors using Allred scoring system. Three cases of cribriform and two cases
from tubular pattern expressed positivity. In the case series selection of our
study cohort there was no association seen in age, gender, site and histological
type of tumour with the expression of oestrogen receptor. Conclusions: Role of
oestrogen is well established in breast cancers, some of salivary gland adenoid
cystic carcinoma also express these receptors and could be involved in the
pathogenesis. Further studies are recommended to seek possible explanation of
variable staining pattern observed in many other studies, and also to determine
the possible therapeutic use of tamoxifen in such tumours.
PMID- 29330973
TI - The Effect Of Sex Education And Life Skills For Preventive Sexual Risk Behaviours
Among University Of Students In Thailand.
AB - BACKGROUND: Currently, the problem of sexual risk behaviour of adolescents has
increased worldwide, including Thailand. This study compared the effectiveness of
promoting life skills to prevent sexual risk behaviours among university students
in the Phayao Province of Thailand. METHODS: A quasi-experimental design was
employed with a pre- and post-test study for a sample of freshmen university
students. The students were then split into an intervention group comprised of
300 students, with a second group of 250 students from the same faculty as the
control group. The intervention group participated in the integrated life skills
model for preventing sexual risk behaviours and participatory learning. The
educational activities included; lectures, brainstorming, group discussion,
roleplaying, game simulations and naming experiences through six weekly life
skills training sessions of 90 minutes each. Data were collected by self
questionnaires and analysed using descriptive statistics and independent sample t
testing. Three different time periods were examined using ANOVA repeated measures
analysis of variance. RESULTS: Compared between the intervention and control
groups determined that implementation of increased knowledge and improved life
skills was statistically significant (p<0.001) in the intervention group. The
intervention group also showed significantly improved communication skills and
behavioural preventive measures towards sexual risk than the control group
(p<0.001). CONCLUSIONS: The life skills model also effectively reduced the sexual
risk behaviours of students at the university. Therefore, this program was
beneficial for the development of strategies to increase self-efficacy and it
should be integrated into the universities' curriculum. In the long-term sexual
risk behaviour changes must be monitored for programme sustainability.
PMID- 29330974
TI - Nucleic Acid Amplification Test For Detection Of West Nile Virus Infection In
Pakistani Blood Donors.
AB - BACKGROUND: The study was planned to determine the presence of West Nile Virus
(WNV) infection in Pakistani blood donors, using Nucleic Acid Amplification Test
(NAT). METHODS: The blood donors for study were selected on the basis of the
standard questionnaire and routine screening results. Six donors were pooled
using an automated pipettor and NAT for WNV was performed on Roche Cobas s 201
NAT system. The reactive pools were resolved in Individual Donation-NAT (ID-NAT)
format and a sample from FFP bags of reactive donations was retrieved. NAT was
again performed on retrieved plasma bag (RPB) sample to confirm the reactive
donations. The donors were also recalled and interviewed about history of illness
related to recent WNV infection. RESULTS: After serological screening of 1929
donors during the study period, 1860 donors were selected for NAT test for WNV
detection. The mean age of the donors was 28+/-8.77 (range: 18-57 years). 1847
(99.3%) donors were male and 13 (0.7%) were female. NAT for WNV identified six
initially reactive pools (0.32%). On follow-up testing with RPB samples, 4 donors
(0.21%) were found confirmed reactive for WNV RNA (NAT yield of 1 in 465 blood
donors). CONCLUSIONS: WNV is a threat to safety of blood products in Pakistan. A
screening strategy can be implemented after a large-scale study and financial
considerations. One of the reduced cost screening strategies is seasonal
screening of blood donors for WNV, with pooling of samples.
PMID- 29330975
TI - Emergency Inguinal Hernia Repair: Comparison Of Desarda's Versus Darning
Technique.
AB - BACKGROUND: Emergency inguinal hernia repair remains the commonest operation
performed by general surgeons all over the world. The aim of this study was to
compare the mean operative time, post-operative pain, wound infection and early
recurrence between Desarda's and Darning emergency inguinal hernia repair.
METHODS: This is a randomized controlled trial conducted at Jinnah Postgraduate
Medical Centre, Karachi. A total of 186 patients of male gender between ages 20
60 years with incarcerated, obstructed and strangulated inguinal hernia were
enrolled in the study. Patients with primary and recurrent inguinal hernias were
excluded. All patients were randomized to Desarda group (n=93) and Darning group
(n=93). RESULTS: Mean operative time in Desarda group was 55.53+/-6.81 minutes
and mean operative time in darning group was 53.06+/-5.51 minutes (p-value
0.007). Mild to moderate pain was found insignificantly higher in Desarda group
75 (80.6%) as compared to Darning group 66 (71%) (p-value 0.170). Wound infection
was found higher in Desarda group 18 (19.4%) as compared to darning group 9
(9.7%) (p-value 0.061). Recurrence was found significantly higher 15 (55.5%) in
Darning group as compared to Desarda group 2 (7.4%) (p-value <0.001).
CONCLUSIONS: No significant difference was observed in the postoperative pain,
wound infection however, significant differences were observed in the mean
operative time and recurrence rates.
PMID- 29330976
TI - Ranitidine Can Potentiate The Prokinetic Effect Of Itopride At Low Doses- An In
Vitro Study.
AB - BACKGROUND: Gastroparesis and GERD occur concomitantly in 40 percent of the
cases. Prokinetic drugs and acid blockers are employed as the main treatment
modality. Ranitidine is an acid blocker with additional prokinetic activity and
Itopride is a known prokinetic drug. This study was designed to observe the
synergistic potentiating prokinetic effect of Ranitidine on itopride on isolated
duodenum of rabbits. METHODS: Ranitidine (10-5-10-3) and itopride (10-6-10-5)
were added in increasing concentrations to isolated duodenum of rabbits and
contractions were recorded on PowerLab Data acquisition unit AHK/214. Cumulative
dose response curves were constructed. The potentiating prokinetic effect of
Ranitidine on itopride was seen by using a fixed dose of ranitidine and
cumulatively enhancing doses of itopride on iWorx. RESULTS: Ranitidine and
itopride produced a dose dependent reversible contraction of the isolated tissue
of rabbits with ranitidine showing a max response of 0.124mV and itopride showing
a maximum response of 0.131mV. Ranitidine was able to potentiate the prokinetic
effect of itopride at low doses but at high dose the effect began to wane off.
CONCLUSIONS: Ranitidine and itopride produce a statistically significant
synergistic potentiating prokinetic effect at low doses in vitro.
PMID- 29330977
TI - Effectiveness Of Horizontal Peer-Assisted Learning In Physical Examination
Performance.
AB - BACKGROUND: All students cannot be individually trained in physical examination
skills due to faculty and time limitations. Peer-assisted learning (PAL) can
solve this dilemma if it is used in undergraduate curriculum. Empirical
effectiveness of horizontal peer-assisted learning model has not been reported
previously. The objective of this study was to compare horizontal peer-assisted
learning (PAL) with expert-assisted learning (EAL) in teaching of physical
examination skills. METHODS: This is a randomized controlled study (Solomon four
group design) carried out at a medical school. A total of 120 undergraduate year
5 students were randomized into two groups to undergo training in four areas of
physical examination. Stratified random sampling technique was used. Group 1 was
trained by EAL while Group 2 by PAL. Half students from both groups were given a
pre-test to assess the testing effect. Both groups were given a post-test in the
form of an OSCE. Independent samples t-test and paired sample t-test were used as
tests of significance. RESULTS: Group 2 scored significantly higher than Group 1.
There was significant difference (p=.000) in mean post-test scores of Group-1
(69.98+/-5.6) and Group-2 (85.27+/-5.6). Difference in mean scores was not
significant (p=.977) between students who had taken the pre-test and those who
had not. CONCLUSIONS: This study has implications in curriculum development as it
provides quantitative evidence indicating that horizontal PAL as a learning
strategy can actually replace, rather than augment, expert-assisted learning in
teaching clinical skills to undergraduate students.
PMID- 29330978
TI - Intramuscular Diclofenac Vs Periprostatic Lidocaine Injection For Controlling
Pain Undergoing Transrectal Ultrasound Guided Prostatic Biopsy.
AB - BACKGROUND: Transrectal ultrasound (TRUS) technique for getting prostatic tissue
for histopathology is now the standard procedure for malignant lesions of the
prostate and imperative diagnostic investigation of patients with clinical specks
of prostatic neoplasia. During TRUS guided biopsy, pain control has been
important issue therefore, highly potent analgesia before this procedure should
be considered on high priority according to current census. Therefore, we
compared intramuscular diclofenac injection with sensory blockade of injection
lidocaine to abolish pain undergoing prostatic biopsy with TRUS technique.
METHODS: Total 200 patients were selected for this study having raised PSA values
and suspicious nodule on Digital Rectal Examination. These patients were
segregated into two groups by randomization. Group "A" received intramuscular
diclofenac and group "B" were infiltrated with lidocaine injection for sensory
blockade. RESULTS: Patients in group A was having mean age of 64.5+/-5.8 years
while for group B patients was 65.6+/-4.9 years (p=0.16). Both groups have
statistically insignificant difference in their mean PSA values (p=0.24) and mean
prostatic volume (p=0.22). The mean pain scores on visual analogue scale in
groups A was 3.5+/-0.8 and in group B it was 2.4+/-0.8 (p<0.001). 60% group A
patients reported with mild or no pain compared to 90% in group B. (p<0.001)..
CONCLUSIONS: Local blockade with lidocaine injection has better pain control as
compared to patients experienced pain with intramuscular diclofenac used for
prostatic biopsy through TRUS technique..
PMID- 29330979
TI - Early Versus Delayed Laparoscopic Cholecystectomy For Acute Cholecystitis.
AB - BACKGROUND: Laparoscopic cholecystectomy is considered the gold standard for the
management of acute cholecystitis but controversy surrounds the timings of the
surgery. Studies are available favouring both early and delayed laparoscopic
cholecystectomy. The objective of this study was to compare early versus delayed
laparoscopic cholecystectomy for acute cholecystitis. METHODS: This quasi
experimental study included 180 patients irrespective of their age and sex
presented at department of Surgery, Lahore General Hospital between January to
December 2014 with a diagnosis of acute cholecystitis were assigned randomly to
early laparoscopic cholecystectomy within 24 h of admission or to initial
conservative treatment followed by delayed laparoscopic cholecystectomy, 6-12
weeks later. RESULTS: The mean operating time was 64.32 min vs. 58.24 min in the
delayed group, conversion rate (early 15.5% vs. delayed 14.4%). The mean
postoperative hospital stay was 1.67 days in the earlier group and 4.38 days in
the delayed group. Overall mortality was zero. CONCLUSIONS: Early laparoscopic
cholecystectomy for acute cholecystitis is safe, offering economic benefit of
much shorter hospital stay and quick recovery.
PMID- 29330980
TI - Comparison Of Efficacy Of Chloroquine And Artemether/Lumafantrine In Treating
Vivax Malaria In Thall And Surrounding Area.
AB - BACKGROUND: Fever is the main complaint in patients reporting to our hospital and
the most common cause of fever in our set up is malaria. The aim of this study
was to know about the clinical response, efficacy and resistance of vivax malaria
to chloroquine in patients reporting to Thall Scouts Hospital. METHODS: All the
adult male patients reporting to Thall Scouts Hospital with fever and other
symptoms of malaria having slide positive vivax malaria were included in the
study. Both thick and thin slide were used for the diagnosis and species
determination of malaria. Age group of the patients was from 18-40 years old. The
study was conducted for the period of two years. RESULTS: Total number of
patients included in the study was 518. Of the 518 patients, 374 (72.2%)
responded to chloroquine and the remaining 144 (27.8%) were given
Arthemether/Lumafantrine combination. Having positive symptoms of malaria total
374 patients treated with chloroquine 171 (45.72%) were asymptomatic after 24
hours, 98 (26.2%) after 48 hours, 78 (20.86%), after 72 hours of treatment while
27 (7.22%) were found to be resistant to chloroquine. Of the 144 patients having
positive malaria treated with Artemether/Lumafantrine 62 (43.06%) were
asymptomatic after 24 hours, 65 (45.14%) after 48 hours, 13 (9.03%) after 72
hours while 4 (2.78%) had still positive symptoms of malaria. CONCLUSIONS: Vivax
malaria in our set up is sensitive to both Chloroquine and
Arthemether/Lumafantrine. As Chloroquine is a cheap and easily available drug, so
it can be safely given to patients with vivax malaria. It will also decrease the
total cost of the disease.
PMID- 29330981
TI - Comparison Of Ziehl-Neelsen Based Light Microscopy With Led Fluorescent
Microscopy For Tuberculosis Diagnosis: An Insight From A Limited Resource-High
Burden setting.
AB - BACKGROUND: Microscopy is the most widely used tool for Tuberculosis screening.
Conventionally, Ziehl-Neelsen (ZN) staining has been the widely used for staining
Acid-Fast Bacilli (AFB) but with the advent of Fluorescent staining, Auramine O
stain is now being adapted as the preferred method for setups with high workload
as it has the advantage of being less laborious, since bacteria fluoresce in
front of a dark background and are easier to count. This study was performed to
compare the efficiency of the two methods in a high-burden, limited resource
setting to see the magnitude of diagnostic accuracy between ZN and Fluorescent
Microscopy, using culture as the standard.. METHODS: Altogether 987 culturally
confirmed cases were considered from the period 36 months during January 2011 to
December 2013 and data were compiled from the records maintained at the
Provincial Tuberculosis Reference Laboratory at Ojha Institute of Chest Diseases,
Dow University of Health Sciences, Karachi. The results from 523 cases examined
using ZN and 464 cases using Fluorescent staining method were compared for
diagnostic accuracy on the basis of Mycobacterial culture results. Smears are
prepared from the clinical samples obtained from presumptive tuberculosis
patients. RESULTS: The results of ZN method showed 94.23% [95% CI 91.32-96.39%]
sensitivity and 84.91% [95% CI 78.38-90.08%] specificity. While FM showed a
sensitivity of 97.15% [95% CI 94.82-98.63%] and specificity of 83.19% [95% CI
74.99-89.56%].. CONCLUSIONS: The results showed that Fluorescent microscopy was
slightly more sensitive than ZN light Microscopy, while specificity of both the
methods were comparable.
PMID- 29330982
TI - Assessment Of Safety Levels In Operation Rooms At Two Major Tertiary Care Public
Hospitals Of Karachi. "Safe Surgery Saves Life".
AB - BACKGROUND: The objectives of this study are to determine the knowledge and
attitude towards surgical safety among the health care professionals including
surgeons, anaesthetist, hospital administrators, and operation room personnel and
raise awareness towards the importance of safe surgery. METHODS: A pilot cross-
sectional study of 543 healthcare providers working in the operating rooms and
the surgical intensive care units was conducted in two tertiary care hospitals,
within a study period of one month. A structured questionnaire was constructed
and an informed verbal consent was taken. The questionnaire was then distributed;
data collected and analysed on SPSS 20.0.. RESULTS: A total of 543 respondents
participated in the study out of which there were 375 (69%) men and 168 (31%)
women. The ages ranged between 23-58 years, mean 40.5+/-24.74. There were110
(20.25%) surgeons, 58 (10.68%) anaesthetist, 132 (24.30%) trainees, 125 (23.02%)
technicians, and were 118 (21.73%) nurses. The question regarding briefing
operation room personnel is important for patient safety was agreed by 532 (98%)
respondents. Amongst the respondents, 239 (44%) did not feel safe to be operated
in their own setup. Team communication improvement through the check list
implementation was agreed by 483 (89%) respondents. 514 (94.7%) opted for the
checklist to be used while they are being operated. That operation room personnel
frequently disregard established protocols was agreed by 374 (69%) respondents.
193 (35.54%) of the respondents stated that it is difficult for them to speak up
in the OR if they perceive a problem with patient care. CONCLUSIONS: Operation
room personnel were not aware of several important areas related to briefing,
communication, safety attitude, following standard protocols and use of WHO
Surgical Safety check list. A pre-post intervention study should be conducted
after formal introduction of the Checklist. Successful implementation will
require taking all stake holders on board and rigorous training workshops,
reinforcing and revisiting.
PMID- 29330983
TI - Ultrasound And Supine Chest Radiograph In Road Traffic Accident Patients: A
Reliable And Convenient Way To Diagnose Pleural Effusion.
AB - BACKGROUND: Portable bed side ultrasound and supine chest radiograph of 80
traumatic patients excluding very clinically unstable patients who subsequently
underwent CT scan chest was done for traumatic effusion showing that ultrasound
had a higher sensitivity than CXR, 88.23% and 77.94%, respectively, and a similar
specificity of 100% and 100%, respectively. Objective of the study is to compare
the diagnostic accuracy of high resolution ultrasound and supine chest x-ray in
detection of pleural effusion in road traffic accident patients keeping plain CT
chest as gold standard. METHODS: This study was conducted in PIMS and PAEC
General Hospital, Islamabad from 1st January to 15th December 2015. The current
study examined total of 80 trauma (blunt and penetrating) patients coming to
emergency departments of both hospitals specifically those who had road traffic
accident history. Their portable bed side ultrasound and supine chest radiograph
were performed for assessing pleural effusion and subsequently CT scan chest was
done for confirmation as it's a gold standard. RESULTS: Using CT findings as gold
standard the sensitivity, specificity, positive predictive value and negative
predictive value was assessed for both ultrasonography and chest radiography and
found to be 88.23%,100%, 100%, 40% and 77.94%, 100%, 100%, 55.55% respectively
with diagnostic accuracy of ultrasound 90% as compared to 81.25% for supine chest
x-rays when compared with gold standard. CONCLUSIONS: Ultrasound and chest x-ray
can be used as a useful and suitable adjunct to CT in road traffic accident
patients as these are easily available, non-invasive, no contrast required, can
be performed on bed side and carries no or little radiation risk.
PMID- 29330984
TI - Polydioxanone Versus Polypropylene Closure For Midline Abdominal Incisions.
AB - BACKGROUND: Midline laparotomy is the most common technique of abdominal
incisions because it is simple, provides adequate exposure to all four quadrants,
and is rapid to open. A major problem after midline laparotomy remains the
adequate technique of abdominal fascia closure. This study was conducted to see
the role of Polydioxanone and Prolene for midline abdominal closure in terms of
postoperative wound infection and wound pain. METHODS: This study was carried out
at surgical unit II, Federal Government Services Hospital Islamabad. Patients
were equally divided in two groups, i.e., A and B. Groups A and B patients
undergone midline abdominal closure with Polydioxanone number 1 and Polypropylene
number 1 sutures respectively. RESULTS: Total 620 patients were included in this
study. Post-operative wound pain score according to Visual analogue scale (VAS)
was compared in terms of no pain (0), mild pain (1-3), moderate pain (4-6),
severe pain (7-9). In group A (Polydioxanone), the frequency and percentages of
no, mild, moderate and severe pain were 101 (32.6%), 95 (30.6%), 81 (26.1%) and
33 (10.6%) respectively, where as in group B (polypropylene) it was 82 (26.5%),
43 (13.9%), 59 (19%) and 126 (40.6%) respectively. Similarly, the frequency and
percentages of post-operative wound infection in group A (Polydioxanone) and
group B (polypropylene) was 105 (33.9%) and 208 (67.1%) respectively.
CONCLUSIONS: Polydioxanone results in less wound pain and wound infection when
compared to Polypropylene.
PMID- 29330985
TI - Medical Students' Perceptions Of Their Learning Environment At Lahore Medical And
Dental College Lahore.
AB - BACKGROUND: The present study was designed to assess medical students'
perceptions of their learning environment at Lahore Medical and Dental College,
Lahore. METHODS: It was a crosssectional descriptive study conducted at Lahore
Medical and Dental College, Lahore. Five hundred and thirty-three students
participated in this study. A questionnaire was used as a study tool, comprising
of demographic information and the 'Dundee Ready Education Environment Measure'
(DREEM) inventory. Data was entered and analyzed using SPSS 21 package. A
comparison of scores between different MBBS classes was done by using ANOVA.
Comparison of scores between gender and high school education was done by using
Mann-Whitney U tests. RESULTS: Study population included 62% females and 32%
males. About 58% of the participants were between 18-21 years and 42% were
between 22-25 years of age. The mean total DREEM score was 120.27/200. The mean
score of the domains: 'Students' perceptions of learning' was 28.31/48,
'Students' perceptions of teaching' was 26.92/44, 'Students' academic self-
perceptions' was 21.37/32, 'Students' perceptions of atmosphere' was 27.72/48,
and 'Students' social selfperceptions' was 16.40/28. Total DREEM and its
subclasses score was significantly higher in F. Sc. students than the students
with A level/American board (p-value <0.001). When DREEM scores were analyzed
according to gender, perceptions of both male and female were positive. Age had
no significant bearing on the total DREEM scores or scores in its subclasses.
CONCLUSIONS: Overall perceptions or experiences of the MBBS students of their
learning environment at Lahore medical and Dental College, Lahore were more
positive.
PMID- 29330986
TI - Use Of Psychoactive Drugs Among Medical Undergraduates In Abbottabad.
AB - BACKGROUND: Psychoactive substance abuse is prevalent among medical
undergraduates of Pakistan, India & Western countries which can adversely affect
the physical & psychological grooming of a medical undergraduate thus threatening
to compromise their role as future physicians & health-care providers in the
society. The objective of the present cross-sectional study was to explore the
prevalence and patterns of psychoactive substance/drug consumption among
undergraduate students of a public sector medical college in Abbottabad. METHODS:
Seven hundred and eighty participants after informed consent were requested to
fill a questionnaire seeking information about their demographics, patterns &
behaviours regarding ten common psychoactive substances of abuse including
(Cigarettes, Benzodiazepines, naswar, cannabis, alcohol, amphetamine, opium,
cocaine, heroin & organic solvents). RESULTS: Overall students who responded were
698 (89.48%). One hundred and fifty (21.49%) admitted to the use of a
psychoactive substance in past or at present. Majority users (71.33%) were males.
Overall (81.33%) users were living in hostel or a rented apartment. Substance
abuse was more prevalent among senior students, i.e., 30.06% & 24.24% in 4th year
& final year MBBS respectively. Majority of the consumers, i.e., 93 (62%) were
falling in an age group between 15-20 years. Main reasons behind substance abuse
were: psychological stress (49.33%) and pleasure seeking (42.67%).
Substances/drugs used by students in order of preference were Cigarettes 115
(76.67%), Benzodiazepines 48 (32%), naswar 42 (28%), Cannabis 41 (27.33%),
Alcohol 24 (16%), Amphetamine 22 (14.67%), Opium 15 (10%), Cocaine 14 (9.33%),
Heroin 11 (7.33%) & Organic solvents 05 (3.33%). Use of more than one substance
was observed in 70 (46.67%) students. CONCLUSIONS: It is concluded that
prevalence of cigarette smoking, naswar, benzodiazepines, cannabis & alcohol is
high among medical undergraduates in Abbottabad which is a matter of concern.
Efforts are needed to create better awareness among them about the hazards of
substance abuse on their health, upcoming professional career and ailing humanity
under their care.
PMID- 29330987
TI - Pattern Of Dyslipidaemia And Its Association With Hypovitaminosis D In Type 2
Diabetes Mellitus.
AB - BACKGROUND: Macrovascular atherosclerosis is an important long-term complication
of type 2 diabetes mellitus. Concurrent dyslipidaemia acts as an additional risk
factor for these complications. Hypovitaminosis D has been associated with
adverse cardiovascular events. These modifiable risk factors of cardiovascular
disease are inter-related. In the presence of an increasing incidence of type 2
diabetes mellitus and its associated metabolic abnormalities and widespread
vitamin D deficiency in Pakistan, this association needs to be investigated. The
purpose of our study was to determine the pattern of dyslipidaemia and its
association with low vitamin D levels in South Asian diabetics. METHODS: The
study was designed as a quantitative cross-sectional study. It was conducted at
the Department of Medicine, Sir Syed College of Medical Sciences and Hospital,
Karachi from January to June 2014. A total of 168 adult consecutive patients with
type 2 diabetes mellitus of both the genders were included. Data was collected
and analysed using SPSS-20.0. The association of dyslipidaemia with vitamin D
status was computed through Chi-square test. RESULTS: We found that dyslipidaemia
is highly prevalent in patients with type 2 diabetes mellitus in Pakistan. High
total cholesterol, LDL cholesterol and triglycerides show significant association
with vitamin D deficiency. CONCLUSIONS: In order to decrease the development of
diabetic complications aggressive management of hyperglycaemia and dyslipidaemia
is required. Vitamin D supplementation may play a dual role in these situations.
PMID- 29330988
TI - Microbiological Profile From Middle Ear And Nasopharynx In Patients Suffering
From Chronic Active Mucosal Otitis Media.
AB - BACKGROUND: Chronic otitis media is described as a tympanic membrane perforation
and ear discharge for more than six weeks duration. Ascending infection from the
nasopharynx into the middle ear cleft has been attributed to prevent resolution
of chronic otitis media. This research aims to determine the association between
the microbiological flora of the nasopharynx with that of the middle ear in
patients suffering from chronic (active) mucosal otitis media.. METHODS: Our
study is a hospital-based cross-sectional survey. It was conducted from December
2015 to February 2017 at the Department of ENT, Combined Military Hospital,
Abbottabad. Ear and nasopharyngeal swabs were obtained from 65 patients of
chronic active mucosal otitis media and sent for microbiological analysis.
Microbiological culture and sensitivity test was performed to identify the
microbial spectrum of each specimen. Performa bearing the result of otoscopy,
aspirate and swabs were completed for middle ear and the nasopharyngeal culture
with reference to each patient. Descriptive statistics and Pearson's chi square
analysis were performed using SPSS-22. RESULTS: Staphylococcus aureus and
Pseudomonas aeruginosa are foremost microorganisms found in otorrhea culture
isolated from patients of chronic active mucosal otitis media. Majority of the
cultures from nasopharynx of these patients did not reveal any growth after
incubation for 48 hours. CONCLUSIONS: A statistically insignificant association
exists between the microbiological spectrum of the middle ear and the nasopharynx
of patients suffering from chronic active mucosal otitis media. Micro organisms'
exposure from a perforated tympanic membrane remains leading cause of persistent
otorrhea, rather than ascending infection through the Eustachian tube.
PMID- 29330989
TI - Hepatitis B And Hepatitis C Virus In Women With First Pregnancy.
AB - BACKGROUND: Hepatitis B and Hepatitis C are amongst the leading causes of
morbidity and mortality in pregnant women throughout the globe. This study is
aimed at determining the frequency of these infections among primigravid females
and the common factors that make them prone to these infections. METHODS: This
cross-sectional study was conducted at Ayub Teaching Hospital, Abbottabad from
December 2015 to May 2016. A total of 174 jaundiced primigravida patients were
included in the study through non-probability consecutive sampling. Blood samples
were sent for HBsAg and anti-HCV ELISA. Samples were analysed by the pathologist
with more than 5 years clinical experience. All data will be analysed using SPSS
16. RESULTS: The mean age of the subjects was 24+/-5.7 years. Six (3.4%) patients
were HBsAg positive and 13 (7.5%) were anti-HCV positive. About 9% of patients
had undergone surgery in their life and 1.7% reported having received blood
transfusion during their life. Thirty-two of them had history of intravenous or
intramuscular injections. History of piercing of body part mostly ear-piercing
for ornaments was present in 170 (97.7%) respondents. However, the frequency of
blood transfusion, surgery and body piercing was not statistically significantly
between HBsAg positive, HBsAg negative, and anti-HCV positive and negative
patients (p>0.05). CONCLUSIONS: The incidence of these viral infections in our
community is on the rise. It emphasizes the need of routine antenatal screening
in pregnant ladies for these viruses and to educate the public about preventive
measures against these infections.
PMID- 29330990
TI - Association Of Quality Of Sleep With Cognitive Decline Among The Patients Of
Chronic Kidney Disease Undergoing Haemodialysis.
AB - BACKGROUND: This study was conducted to determine the association between the
subjective quality of sleep and cognitive decline among the patients of chronic
kidney disease (CKD) undergoing haemodialysis. METHODS: In this cross-sectional
study 106 patients of chronic kidney disease (CKD) undergoing haemodialysis at a
tertiary care hospital in Rawalpindi, Pakistan were included in the final
analysis. Cognitive decline was measured by British Columbia Cognitive Complaints
Inventory (BC-CCI). Sleep quality was measured by using the Pittsburgh Sleep
Quality Index (PSQI). Relationship of age, gender, marital status, education,
occupation, BMI, duration of dialysis, dialysis count per week, family income,
tobacco smoking and use of naswar was assessed with the cognitive decline..
RESULTS: Out of 106 patients screened through BC-CCI and PSQI, 13.1% had no
cognitive decline while 86.9% had significant cognitive decline. Relationship
between quality of sleep and cognitive decline was significant on binary logistic
regression.. CONCLUSIONS: This study showed significant relationship between the
sleep quality and cognitive decline among the patients of CKD undergoing
haemodialysis. The findings of our study also call for a greater degree of
understanding of the physical and psychological state of patients of CKD
undergoing haemodialysis.
PMID- 29330991
TI - Diaphyseal Nutrient Foramina In Dried Human Adult Long Bones Of Lower Limb In
Pakistan.
AB - BACKGROUND: osteogenesis needs circulation of blood in the bones. Bone growth,
repair of fracture, maintenance of bone vitality and other injures also need
blood circulation in proper way. Blood is allowed to flow via holes in the
diaphysis, which are called as nutrient foramina. METHODS: The crosssectional
study was done in the department of Anatomy, Ayub and Khyber Medical College
(Osteology Sections). The aim was to observe diaphyseal nutrient foramina in the
human long bones of the lower limb. The study was done on 90 long bones of lower
limb consisting of 30 femora, 30 tibiae and 30 fibulae. Of all these bones, sex
was not determined. All the bones were macroscopically observed. For the number
of the foramina, simple counting was done. The foraminae 1 mm away from the
borders were counted. All positions were seen macroscopically. For direction and
obliquity, stiff wire was used. RESULTS: We studied 90 long bones of lower limb.
About 80% of long bones of lower limb showed single nutrient foramina. About 18%
of lower limb long bones showed two nutrient foraminae. In cases of femora
nutrient foraminae were directed proximally. In cases of fibulae and tibiae most
of the foramina were directed distally. CONCLUSIONS: the study has provided
additional information on the foramina index, morphology and topography of the
nutrient foramina. In the lower limb long bones, the anatomical data is important
for the clinicians as the micro-vascular bone transfer is becoming popular. This
morphological data can be used by the forensic experts in identification through
different landmarks in bones development giving an aid in medicolegal work.
PMID- 29330992
TI - Client Satisfaction And Decision Making Amongst Females Visiting Family Planning
Clinics In Hyderabad, Pakistan.
AB - BACKGROUND: Family Planning is the basic right of the human being. It involves
decision regarding the number of children and desired space between children by
the couple themselves. Quality services involving multiple dimensions build the
confidence of the clients and lack of quality is one of the constraints behind
incomplete coverage of family planning. Objectives of the current study were to
determine the client satisfaction, decision-making process and various influences
on clients in adopting family planning methods. METHODS: This cross-sectional
study was conducted at Family Planning Centre of Liaquat University Hospital,
Hyderabad in 2016. Quality of the family planning services and satisfaction with
the services were assessed through responses obtained from women selected
purposively and visiting family planning centre through exit interviews with
structured pretested and reliable questionnaire after taking the written consent.
RESULTS: Access to Family Planning Centre was not an issue in 92% cases but only
31% respondents were appropriately greeted, 77% faced blank expression and 13%
received sufficient privacy. Health problems and socioeconomic conditions were
inquired by 41% and18% providers respectively, while motivating force for service
use was mother in law in most 35% cases. Health workers were successful in
clarifying misinformation (86%) and explaining side effects (71%) but only 21%
respondents were satisfied with services. Respondents are influenced by family
and health care providers while making decision and type of influence was
considered positive by 83% respondents. CONCLUSIONS: Training and monitoring
system be strengthened at family planning centres to improve quality of services
while important influencing relations be focused for family planning education to
improve utilization of services.
PMID- 29330993
TI - Chemical Composition Of Stones In Paediatric Urolithiasis.
AB - BACKGROUND: Chemical composition of stones is one of the important diagnostic
criteria for aetiology of stone formation and treatment to prevent recurrence.
This paper reports composition of stones in children at a tertiary hospital by
Fourier Transformation Infrared Spectroscopy (FTIR). METHODS: Between January
June 2015, 412 urinary stones from children were analysed by FTIR. Chi-square
tests were used for the comparison of categorical measurements between groups.
All reported values were 2-sided and statistical significance was considered at p
value <=0.05. RESULTS: Of the 412 stones, 263 (63.8%) were renal, 101(24.5%)
bladder and 48 (11.7%) ureteric. The mean age of children was 7.15+/-4.13 years
with a M:F ratio 2.4:1. Of the 412 stones, 144(34.9%) were pure stones composed
of one compound and 268(65.1%) were mixtures. Frequency of compound in stones was
Ammonium Acid Urate (AAU) (65%), Calcium Oxalate (CaOx) (76.9%), Uric Acid (5%),
Calcium Phosphate Apatite (7%), Whitlockite (8.4%), Struvite (4%), Cystine
(0.72%) and Xanthine (2.11%). Frequency of compounds analysed in three ages
groups 0-5, 6-10 and 11-15 years showed high frequency of AAU (73%) in 0-5 years
as compared to (60%) in 11-15 years (p<0.018). CaOx (90%) in 11-15 as compared to
(62.5%) in 0-5 years (p<0.001). Bladder stones were more prevalent in children 0
5 years (32%) vs 19% in 11-15 years (p<0.004) while renal were 75% in 11-15 years
and 54% in 0-5 years (p<0.04). CONCLUSIONS: AAU stones known to be associated
with malnutrition and chronic diarrhoea are highly prevalent in paediatric stones
formers in our population in the kidney, bladder and ureter.
PMID- 29330994
TI - Pattern Of Causative Micro-Organisms In Catheter Related Blood Stream Infections
In Dialysis Patients: Experience From Saudi Arabia.
AB - BACKGROUND: Catheter related blood stream infections (CRBSI) are the leading
cause of morbidity in HD patients. The majority of these infections relate to
haemodialysis catheters. There is a paucity of local data on microbial agents
responsible for CRBSI in our region. This prompted our study. METHODS: This
Prospective observatory survey was conducted in Department of Nephrology, King
Fahd Hospital, Hofuf KSA from Nov 2014 to Jan 2017 (26 months). It was performed
on dialysis patients with HD catheters who developed features of CRBSI. Blood
cultures were taken from the patient and cultured microorganisms were observed
and stratified according to type and prevalence in relation to age gender and
comorbidities. RESULTS: There were 210 distinct episodes of CRBSI. 61.5% (n=129)
were due to gram negative microorganisms and 38.5% (n=81) were due to Gram
positive microorganism. Fifty-three events were due to Coagulase Negative
Staphylococcus aureus. Enterobacter cloachae accounted for 28 events. Pseudomonas
19 events, Enterococcus faecalis 13, Klebsiella 11, Acinitobacter accounted for 8
events. CRBSI was observed more frequently in males (n=136), diabetics (n=113)
and in age 40 years+/-19 years(n=97). CONCLUSIONS: Gram negative microorganisms
were more commonly responsible for CRBSI in our settings. Enterobacter cloachae
was most common gram-negative microorganism responsible for CRBSI, a finding not
observed in other studies. There was significant predisposition to diabetics,
male gender and middle age group. We need further studies to observe antibiotics
sensitivity of microorganisms so that we can standardize empirical antibiotics in
cases of CRBSI.
PMID- 29330995
TI - Depression In Myocardial Infarction Patients At Ayub Teaching Hospital
Abbottabad.
AB - BACKGROUND: There is a considerably high prevalence of depression in post
myocardial infarction (MI) patients. This study was designed with an aim to
detect depression in patients with acute MI admitted to the CCU at Ayub Teaching
Hospital Abbottabad.. METHODS: This descriptive crosssectional study enrolled 246
male and female patients with acute MI. The patients were interviewed on the 3rd
day of admission and their answers were marked according to the HADS-D scale.
RESULTS: With a cut-off score of 11, the frequency of depression in study
participants was 27.24% (n=67). No statistically significant association was
found between the age and sex of patients and depression. CONCLUSIONS: Depression
is fairly common following acute MI and the management plans should include a
consultation with psychiatric for individualized management of depression in post
myocardial infarction patients..
PMID- 29330996
TI - Missed Immunization Opportunities Among Children Under 5 Years Of Age Dwelling In
Karachi City.
AB - BACKGROUND: Immunization is the safest and effective measure for preventing and
eradicating various communicable diseases. A glaring immunization gap exists
between developing and industrialized countries towards immunization, because the
developing countries including Pakistan are still striving to provide basic
immunization to their children. The purpose of this study was to access the
prevalence and factors of missing immunization among under 5-year children of
Karachi.. METHODS: A cross sectional study was conducted from June 2015 to
October 2015 among different outpatient clinics of Karachi. Parents who had child
less than 5 year of age were approached by non-probability purposive sampling.
Data was analysed by using Statistical Package of Social Sciences. RESULTS: There
were around 59.09% (n=156) and 64.43% (n=165) parents who have correctly
responded regarding the number of essential immunization visit during the first
and second year of their child life respectively. About 28.12% (n=108) parents
responded that they do not know about the name and number of missed doses of
vaccines. 31.78% (n=122) parents responded that their children have missed either
one or more than one doses of routine immunization vaccines. Of which 34.42%
(n=42) children have missed more than one vaccine. Lack of knowledge regarding
immunization schedule 28.68% (n=34), concern about vaccine side effects 21.31%,
(n=26), child sickness 17.21% (n=21), and lack of trust about government 10.65%,
(n=13) were the major barriers identified by parents for missed immunization
opportunities. CONCLUSIONS: Parents have inadequate knowledge regarding routine
immunization visits, immunization schedule and vaccine doses. The practices of
parents for routine childhood immunization are also poor. Parents refuse to
immunize their child because of lack of immunization visit knowledge and also
because of their doubts regarding vaccine potency and side effects. A proper
system of immunization promotion, advocacy and reminder systems with proper
follow-up mechanism need to be developed by all healthcare centres.
PMID- 29330997
TI - Comparison Of Different Formulations Of Vitamin D.
AB - BACKGROUND: Vitamin D Deficiency (VDD) is responsible for a wide spectrum of
clinical diseases and vitamin D deficiency prevalence is frightening in most
parts of the world including Pakistan. Therefore, supplementations of vitamin D
are used in the population at high risk for the prevention and the treatment of
vitamin D deficiency. Vitamin D supplementation comes in various formulations
both oral and intramuscular. Cholecalciferol is the most commonly used
preparation which is given through these routes of administration. There is need
to study the fact that how much vitamin D levels are raised after administration
of these different formulations as this can be a pivotal factor in determining
dosage and route of vitamin D3. METHODS: This cross-sectional study conducted on
320 cases and compared the efficacy of various Vitamin D3 preparations in raising
Vitamin D levels conducted in Department of Endocrinology and Metabolism,
Services Hospital, Lahore from February to July, 2016. Blood serum was drawn for
vitamin D level in the cases at the time of presentation and after treatment.
RESULTS: Three hundred & twenty patients were enrolled in study and divided into
four groups (A, B, C, D). There was no significant difference between groups (A,
B, C, D) in change in vitamin d levels after 3 months of treatment (p-Value
0.446). CONCLUSIONS: Different preparations of vitamin D are equally effective in
raising vitamin D levels at 12 weeks. However, there is a need to conduct large
scale studies to further validate these results.
PMID- 29330998
TI - Histomorphological Effects Of Hunger Stress On Ovaries.
AB - BACKGROUND: Incidence of stress is on the rise in our daily life involving
various neurobiological, endocrinological and behavioral changes. Hunger stress
has a potent influence on mental, physical, and reproductive health by affecting
the hypothalamic-pituitary gonadal axis. METHODS: It was a laboratory based
randomized control trial. Adult female mice (BALB-c strain) weighing 25-27 grams
on first day of estrous cycle were taken in two groups (ten each). Group A was
kept in normal environment of animal house for one month. Group B was given
hunger stress by restricting the diet to about 50% per day for one month. Right
ovaries of the animals were dissected out and observed for shape, color, and
weight. Histological slides were prepared for the count of primary, secondary,
and tertiary follicles. RESULTS: Statistically significant decrease in animal and
ovary weight with significant fall in ovarian follicles was observed.
CONCLUSIONS: Hunger stress affects the ovaries by reducing its weight and number
of follicles.
PMID- 29330999
TI - Reasons Of Self-Discharge From Nursery Of A Tertiary Care Hospital.
AB - BACKGROUND: Patients who leave against medical advice (LAMA) from a health
facility is a recognized problem. In neonatology practice this issue is
particularly sensitive as repercussions can be severe. The purpose of this study
was to evaluate the factors influencing the decision of parents to self-discharge
their babies against medical advice. METHODS: This descriptive case series was
conducted in the Department of Neonatology, of the Children's Hospital and the
Institute of Child Health, Lahore from January to June 2015. A total of 240
patients who self-discharged/were included. RESULTS: There were (59.6%) males and
(40.4%) females with a male to female ratio of 2:1.5. Term babies constituted
(67.9%), spontaneous vaginal deliveries (59.1%) and (55.8%) were delivered at
hospitals. Seventy seven new-borns (32.2%) had birth asphyxia followed by
neonatal sepsis (27.9%). Sixty four (64.5%) self-discharged within first week of
admission. More babies were signed LAMA at week end (32.1%). Likewise (53.1%)
babies were self- discharged during the night shift. Highest rate of LAMA was
seen in parents belonging to low socioeconomic class (72.1%). Ninety eight
parents (40.8%) had no formal education while well-educated parents were found to
be 35 (14.6%). The commonest reason for selfdischarge was "perceived poor
clinical outcome" (36.7%) by parents. CONCLUSIONS: Multiple factors were
implicated in self-discharges from neonatology unit. Commonest reasons cited by
parents were perception of poor clinical outcome and family pressures. Other
contributory factors were male gender; those delivered vaginally, diagnosis of
birth asphyxia, first week of life, at weekends and night hours. Low
socioeconomic class and education of parents was also a major causative factor.
PMID- 29331000
TI - Evaluation Of Peer Assisted Learning In Evidence Based Medicine Course: A Pilot
Study At University Of Glasgow.
AB - BACKGROUND: Peer Assisted Learning (PAL) is a well-established approach in
learning and is increasingly being utilized in the medical education system. It
is a process where active help of peer group members is taken for learning. This
study aimed to look at the impact of peer assisted learning on the students at
the end of the session. METHODS: Sixteen Postgraduate students attending Evidence
Based Medicine (EBM) course spanning over two semesters (6 months each) were
recruited. It was a cross sectional study and non-probability convenience
sampling technique was used for gathering data. All students enrolled in EBM
course conducted an hour-long PAL session during the coursework. At the end of
the semester a link to an online questionnaire was sent to all the participants.
A set of both open and closed ended questions were included in the questionnaire.
RESULTS: Response rate was 87.5%, 14 out of the 16 students completed the
questionnaire. The results showed an affirmative change in the behaviour and
attitude of the participants' after the workshops. Majority of the respondents
were of the opinion that it was a valuable experience and they benefitted through
involvement in the process. Most of the postgraduate students suggested that it
should be implemented in post graduate studies especially medical education.
CONCLUSIONS: PAL is more interactive and informal way of teaching and it helps in
the professional development, if peers from different specialties are gathered.
However, study with a larger sample size are suggested to prove the
generalizability of this assertion.
PMID- 29331001
TI - Depression And Associated Factors: A Cross-Sectional Study Using Beck Depression
Inventory.
AB - BACKGROUND: Mental health disorders are becoming an increasingly common
occurrence worldwide and present a major public health concern. Depression has
been recognized as a major contributor in mental health disability burden. This
study aims to determine the frequency of depression among individuals presenting
at a rural health facility in Lahore and to identify the risk factors associated
with it.. METHODS: A cross sectional study was conducted at Rural Health Centre
Kahna Nau, Lahore from January to April 2017. A sample of 384 consenting
individuals presenting at the rural health facility were selected through
consecutive sampling technique. Beck Depression Inventory (BDI), was used to
assess the level of depression amongst the respondents. We categorized the BDI
score for this study into BDI >=20 as "depressed" and BDI <20 as "non-depressed".
Data was entered and analysed by using SPSS 16.0. Chi-square test was carried out
to identify factors associated with depression, significant at a p-value of
<=0.05. RESULTS: Out of total, 258 (69.5%) respondents were males with 197 (53%)
in age category of 25-44 years. BDI scale showed 84 (23%) respondents to be
suffering from depression. Age (p=0.002), income (p=0.003), marital status
(p=0.023), educational status (0.011), family structure (p=0.041), history of
hospitalization (p=0.003), smoking status (0.012) and co-morbidity (p=0.001) were
significantly associated with depression. CONCLUSIONS: Our study found a
substantial proportion of patients' who were suffering from depression. Age,
income, marital status, educational qualification, family structure, co-morbidity
and smoking status were significantly associated with depression.
PMID- 29331002
TI - Genetics Of Human Hereditary Hearing Impairment.
AB - Hereditary hearing impairment is heterogeneous type of disorder which can be
caused due to environmental as well as genetical factors. Two distinct types of
hereditary hearing loss are syndromic or non-syndromic. Non-syndromic hearing
loss is further categorized as autosomal recessive, autosomal dominant, X-linked
and mitochondrial deafness. Autosomal recessive occurs more frequently as
compared to autosomal dominant. Mutations in various genes are responsible for
hereditary hearing impairment. To date, about 99 autosomal recessives and 67
autosomal dominant genes for deafness have been discovered. Some of important
genes include GJB2, JGB6, GJB3 which encodes gap junction proteins, MYO7A, MYO15A
encodes myosine proteins, OTOF encodes otoferlin, and SLC26A4 encodes anion
exchanger protein. Up till now, the mutation in GJB2 gene occurs more frequently
in different population of the world and cause autosomal recessive hearing
impairment. The purpose of this review article was to explore the mutation and
function of those muted genes which encode different type of protein and
responsible either for autosomal recessive or autosomal dominant hearing
impairment.
PMID- 29331003
TI - Oral Sildenafil Use In Neonates With Persistent Pulmonary Hypertension Of
Newborn.
AB - BACKGROUND: The prevalence of PPHN has been estimated at 1.9 per 1000 live
births. After the discovery of iNO's, its efficacy and benefit in PPHN is well
established. Even in the best of centers equipped with iNo and ECMO the mortality
is around 20%. Also, iNO is expensive and difficult to administer and monitor
which makes it difficult choice in our part of the world. Furthermore About 40%
of patients do not respond or have rebound pulmonary hypertension after
discontinuation. Owing to these reasons, other treatment modalities like
phosphodiesterase inhibitors such as Sildenafil need to be evaluated. METHODS: We
report a retrospective case series of eighteen patients with PPHN admitted in
NICU and treated with oral sildenafil. RESULTS: Three (17%) babies had mild, 5
(28%) moderate and 10 (55%) severe PPHN based on echocardiography. Sildenafil was
started on all patients on a mean of 1.67 days and stopped on mean 12.6 days.
Initial fio2 was 100%, which after starting sildenafil decreased gradually to 40%
on mean 10 days. Average length of stay in NICU was 13 days. Twelve (67%)
patients survived whereas 6 (33%) expired (Figure 2). No improvement in oxygen
Index after 36 hours (p<0.05) was the independent predicting risk factor for PPHN
related mortality in the expired patients. CONCLUSIONS: Oral sildenafil can be a
used in conjunction with other treatment modalities for PPHN especially in
resource limited settings. However further studies regarding its comparative
efficacy need to be done.
PMID- 29331004
TI - Cholecystectomy For Gall Stones In 26 Months Old Child.
AB - Cholelithiasis is a major cause of morbidity worldwide. The incidence of gall
stone in children in Pakistan has not been sufficiently studied and is
increasingly being detected: the reason may be a true rise in the incidence or an
improvement in diagnosis due to liberal use of diagnostic facilities and thus the
increased opportunity to detect disease. A healthy 2 years and 2 months old male
child presented to outpatient with history of recurrent attacks of pain abdomen
and anorexia. Ultrasonography showed a 0.6 mm stone, inflammation and
pericholecystic fluid. Open cholecystectomy was performed under general
anaesthesia. A distended gall bladder with multiple very small calculi was
removed. Post-operative stay was uneventful and patient was allowed oral feeds
after 24 hours.
PMID- 29331005
TI - Pregnant Lady With Undiagnosed Hodgkin's Disease Presenting As Secondary
Sclerosing Cholangitis.
AB - Hodgkin's lymphoma. A 25 years old lady, 34 weeks primigravida was referred from
the Emergency Department to the Medical Unit Khyber Teaching Hospital-MTI,
Peshawar with four weeks of fever, progressive jaundice, pruritus, night sweats
and weight loss. LFTs showed cholestatic picture, ERCP showed scanty intrahepatic
giving beading and autumn tree appearance typical of sclerosing cholangitis. CBD
was normal. Doppler U/S of hepatic and portal vein reported normal. She was
started on steroids, ursodeoxycholic acid and antibiotics 3rd generation
cephalosporins to which she did not respond well. This prompted a Liver biopsy
which showed Hodgkin's disease having mixed cellularity. She was shifted to
specialized oncology unit for further management where she died of irreversible
liver damage. This is a rare case of secondary sclerosing cholangitis in
Hodgkin's lymphoma of liver and the first case reported to our Hospital.
PMID- 29331006
TI - Outbreak Of Extensively Drug Resistant Stenotrophomonas Maltophilia In Burn Unit.
AB - Stenotrophomonas maltophiliais an emerging cause of nosocomial infections. We
report an outbreak of XDR-Stenotrophomonas maltophilia infection from burn unit
of a tertiary care hospital in July 2016. The strain isolated was resistant to
all antimicrobials tested but colistin. Outbreak investigation was carried out
which subsided after timely intervention. Patients were treated adequately by
Colistin.
PMID- 29331007
TI - Anaesthetic Management Of Nesidioblastosis In Two Infants.
AB - Nesidioblastosis is the most common cause of non-transient, recurrent and
persistent hypoglycaemia in neonates and infants. It is a disorder of diffuse
proliferation of beta cells of the pancreas leading to hyperinsulinemia and
hypoglycaemia. The main aim is to prevent the severe episodes of hypoglycaemia
which can cause damage to the brain and/or mental retardation. In this case
report we present two cases of nesidioblastosis and their perioperative
anaesthetic course for near-total pancreatectomy. First case was a 7 months old
female who had repeated episodes of convulsions since birth. Second case was a 4
month-old female child who again presented with seizures. The challenges faced in
the perioperative period were the management of perioperative blood glucose
levels and haemodynamic stability.
PMID- 29331008
TI - Atypical Presentation Of Rickettsial Spotted Fever.
AB - Acute febrile illness is a common entity in tropics and often is challenging due
a host of pathogenic bacteria, viruses and fungi. Extensive work up is required
for better management. Rickettsiosis is uncommon and hence comes lower down in
the differentials of multiorgan failure being superseded by the more common
diseases as malaria, enteric fever and Dengue. We document a case of young male
presenting with high grade fever, multiorgan dysfunction (hepatic, renal,
neurological and respiratory involvement), conjunctival suffusion, retiform rash
and without lymphadenopathy. The diagnosis was further challenging because the
rashes appeared late at 8th day in the course of illness, unlike the typical
disease where rashes come on early in day 3-6 of the disease. Patient responded
to timely treatment with doxycycline. Thus, a high index of suspicion is needed
to diagnose Rickettsiosis in geographical areas apparently free of the disease.
PMID- 29331009
TI - Cyanoacrylate Injury To The Ear Canal.
AB - This is a case regarding a 35-year-old gentleman who presented to the Accident
and Emergency department at Walsall Manor Hospital. He had mistakenly placed
cyanoacrylate ('superglue') into his right ear canal in the early morning. In
terms of its removal, an initial attempt was made in the Ear, Nose and throat
(ENT) outpatient clinic which proved to be unsuccessful due to the amount of
discomfort it caused the patient. Therefore, it had to be removed under general
anaesthesia.
PMID- 29331010
TI - Implants For Extracapsular Neck Of Femur Fracture Dynamic Hip Screw Versus
Intramedullary Nailing.
AB - Neck of femur fractures are the most prevalent type of injury in elderly trauma
patients. Both intra and extra capsular type of fractures are equally distributed
in the given population. Traditionally, Extra capsular fractures are fixed with
Dynamic Hip screw or Intra medullary nailing based on the type of fracture. NICE
(National Institute of Clinical Excellence) recommends fixing 31-A1 and 31-A2
fractures with DHS (Dynamic Hip Screw) whereas AO recommends fixing 31-A1 with
DHS and 31-A2.1 subtype with DHS and 31-A2.2 and 31-A2.3with IMN (Intra medullary
nail). In regional trauma centre 178 patients, 125 females and 53 males with
extra capsular neck of femur fractures fixed were selected in a retrospective
study. The data was spanning over a period of 1 year. Fractures were classified
as per AO classification by two registrars. The implant selection was analysed in
terms of the short term out come to find out the cost effectiveness of one over
the other. The quality of reduction was assessed as per standard criteria and
consideration of lateral femoral wall thickness was taken into account to assess
the stability of fracture. The study found more risk of peri prosthetic fractures
associated with Intra medullary nailing as compared to Dynamic Hip screw and more
risk of Varus collapse was found to be associated with DHS as compared to IM
Nail. Moreover, despite of Nail being costly as compared to DHS, the study did
not reveal its superiority in terms of inpatient hospital stay. In appropriately
selected patient DHS provides results in terms of hospital stay, revision rate
and wound complications comparable to IM Nail in the short term justifying its
use in the above-mentioned fracture patterns as per the standard National
Institute of clinical Excellence guidelines.
PMID- 29331011
TI - Transfusion-Related Acute Lung Injury In A Paediatric Intensive Care Unit Of
Pakistan.
AB - Background: Transfusion-Related Acute Lung Injury (TRALI) is a major cause of
transfusionrelated morbidity and mortality in the intensive care unit setting.
There is a paucity of such data from Pakistan. The purpose of this study is to
assess the incidence and outcome of TRALI in critically ill children admitted in
a pediatric intensive care unit (PICU) of Pakistan. Methods: This is a
retrospective cohort study of all critically ill or injured children who
developed TRALI or "possible" TRALI after blood transfusion based on Canadian
Conference Consensus criteria in a closed multidisciplinary-cardiothoracic PICU
from January 2012 to June 2016. The demographic, pertinent clinical data,
transfusion-related variables and outcome of all cases of TRALI were recorded.
Results: Of total 2975 admissions in the PICU during study period, 35.8% (1066)
received 5124 blood components. Eleven cases developed TRALI in our cohort. The
incidence of TRALI was 1.03% per patient transfused and 0.19% (19/100,000 per
blood product transfused). Median age was 8 (range 1-14) yr., 70 % (n=8) were
male. Mean PRISM-III score was 16.3+/-6.7. Mean time interval for onset of TRALI
was 2.73+/-1.67 hr. The postoperative cardiac surgical and hematology-oncology
patients were most common categories (63.6%). Plasma and platelets were the most
commomly identified trigger of TRALI. The case-specific mortality was 63.6% and
the overall mortality was 10.7% (p<0.0001). Conclusions: The incidence of TRALI
in critically ill children is low, but is associated with high mortality.
Critically ill children with high PRISM-III score, postoperative cardiac surgical
and hematology-oncology patients are often affected by TRALI.
PMID- 29331012
TI - Capillary Haemangioma Of Lower Lip In An African Patient.
PMID- 29331013
TI - Epiploic Appendagitis.
PMID- 29331014
TI - Biochemical Characterization of Recombinant Thermostable Cohnella sp. A01 beta
Glucanase
AB - Background: Typically, non-cellulytic glucanase, including fungi and yeast cell
wall hydrolyzing enzymes, are released by some symbiotic fungi and plants during
the mycoparasitic fungi attack on plants. These enzymes are known as the defense
mechanisms of plants. This study intends to investigate the biochemical
properties of beta-1,6-glucanase (bg16M) from native thermophilic bacteria,
Cohnella A01. Methods: bg16M gene was cloned and expressed in E. coli BL21 (DE3).
The enzyme was purified utilizing Ni-NTA nikcle sepharose column. Pustulan and
laminarin were selected as substrates in enzyme assay. The purified bg16M enzyme
was treated with different pH, temperature, metal ions, and detergents. Results:
The expressed protein, including 639 amino acids, showed a high similarity with
the hydrolytic glycosylated family 30. The molecular weight of enzyme was 64 kDa,
and purification yield was 46%. The bg16M demonstrated activity as 4.83 U/ml on
laminarin and 2.88 U/ml on pustulan. The optimum pH and temperature of the enzyme
were 8 and 50 degrees C, respectively. The enzyme had an appropriate stability
at high temperatures and in the pH range of 7 to 9, showing acceptable stability,
while it did not lose enzymatic activity completely at acidic or basic pH. None
of the studied metal ions and chemical compounds was the activator of bg16M, and
urea, SDS, and copper acted as enzyme inhibitors. Conclusion: Biochemical
characterization of this enzyme revealed that bg16M can be applied in beverage
industries and medical sectors because of its high activity, as well as thermal
and alkaline stability.
PMID- 29331017
TI - Kv4 channels to kisspeptin neurons: 'Let's (not) go steady'.
PMID- 29331016
TI - A candidate functional SNP rs7074440 in TCF7L2 alters gene expression through C
FOS in hepatocytes.
AB - The SNP rs7903146 at the transcription factor 7-like 2 (TCF7L2) locus is
established as the strongest known genetic marker for type 2 diabetes via genome
wide association studies. However, the functional SNPs regulating TCF7L2
expression remain unclear. Here, we show that the SNP rs7074440 is a candidate
functional SNP highly linked with rs7903146. A reporter plasmid with rs7074440
normal allele sequence exhibited 15-fold higher luciferase activity compared with
risk allele sequence in hepatocytes, demonstrating a strong enhancer activity at
rs7074440. Additionally, we identified C-FOS as an activator binding to the
rs7074440 enhancer using a TFEL genome-wide screen method. Consistently,
knockdown of C-FOS significantly reduced TCF7L2 expression in hepatocytes.
Collectively, a novel enhancer regulating TCF7L2 expression was revealed through
searching for functional SNPs.
PMID- 29331018
TI - Interplay of SpkG kinase and the Slr0151 protein in the phosphorylation of
ferredoxin 5 in Synechocystis sp. strain PCC 6803.
AB - In Synechocystis 6803, the ferredoxin 5 (Fd5) phosphoprotein and the S/T protein
kinase SpkG are encoded by the slr0148 and slr0152 genes, respectively, which
belong to the slr0144-slr0152 cluster. Using a targeted proteomic approach, we
showed that SpkG is responsible for the phosphorylation of Fd5 on residues T18
and T72. Sequence alignments and Fd5 structure modelling suggest that these
phosphorylation events modulate protein-protein interaction. Furthermore, Fd5
phosphorylation is affected by the Slr0151 protein encoded by the gene preceding
spkG in the gene cluster. We propose that Slr0151 functions as an auxiliary
protein in the regulation of the ratio between phosphorylated and
nonphosphorylated forms of Fd5.
PMID- 29331015
TI - Detection of human disease conditions by single-cell morpho-rheological
phenotyping of blood.
AB - Blood is arguably the most important bodily fluid and its analysis provides
crucial health status information. A first routine measure to narrow down
diagnosis in clinical practice is the differential blood count, determining the
frequency of all major blood cells. What is lacking to advance initial blood
diagnostics is an unbiased and quick functional assessment of blood that can
narrow down the diagnosis and generate specific hypotheses. To address this need,
we introduce the continuous, cell-by-cell morpho-rheological (MORE) analysis of
diluted whole blood, without labeling, enrichment or separation, at rates of 1000
cells/sec. In a drop of blood we can identify all major blood cells and
characterize their pathological changes in several disease conditions in vitro
and in patient samples. This approach takes previous results of mechanical
studies on specifically isolated blood cells to the level of application directly
in blood and adds a functional dimension to conventional blood analysis.
PMID- 29331019
TI - Cis-regulator runaway and divergence in asexuals.
AB - With the advent of new sequencing technologies, the evolution of gene expression
is becoming a subject of intensive genomic research, with sparking debates upon
the role played by these kinds of changes in adaptive evolution and speciation.
In this article, we model expression evolution in species differing by their
reproductive systems. We consider different rates of sexual versus asexual
reproduction and the different type of parthenogenesis (apomixis and the various
modes of automixis). We show that competition for expression leads to two
selective processes on cis-regulatory regions that act independently to organism
level adaptation. Coevolution within regulatory networks allows these processes
to occur without strongly modifying expression levels. First, cis-regulatory
regions such as enhancers evolve in a runaway fashion because they automatically
become associated to chromosomes purged from deleterious mutations ("Enhancer
Runaway process"). Second, in clonal or nearly clonal species, homologous cis
regulatory regions tend to diverge, which leads to haploidization of expression,
when they are sufficiently isolated from one another ("Enhancer Divergence
process"). We show how these two processes cooccur and vary depending on the
level of outcrossing, gene conversion, mitotic recombination, or recombination in
automictic species. This study offers thus a baseline to understand patterns of
expression evolution across the diversity of eukaryotic species.
PMID- 29331020
TI - Human phenotypes caused by PIEZO1 mutations; one gene, two overlapping
phenotypes?
AB - PIEZO1 is a large mechanosensitive ion channel protein. Diseases associated with
PIEZO1 include autosomal recessive generalised lymphatic dysplasia of Fotiou
(GLDF) and autosomal dominant dehydrated hereditary stomatocytosis with or
without pseudohyperkalemia and/or perinatal oedema (DHS). The two disorders show
overlapping features, fetal hydrops/perinatal oedema have been reported in both.
Electrophysiological studies suggest opposite mechanisms of action: the mutations
identified in GLDF patients cause a loss-of-function mechanism of disease and
mutations in DHS patients cause gain of function. This raises the question: Is
the pathogenic disease mechanism behind the fetal oedema the same in the two
phenotypes? In this Symposium Review, we will discuss the two conditions and
highlight key questions that remain to be answered. For instance, the perinatal
oedema often resolves soon after birth and we are still at a loss to understand
why. Are there any mechanisms which could compensate for the faulty PIEZO1 in
these patients? Are there physiological changes at birth that are less reliant on
the function of PIEZO1? Thus, there is a clear need for further studies into the
two disorders, in order to fully understand the role of PIEZO1 in health and
disease.
PMID- 29331021
TI - Onset, progression and resolution of experimental peri-implant mucositis at
different abutment surfaces: A randomized controlled two-centre study.
AB - OBJECTIVES: To assess the onset, progression and resolution of experimentally
induced peri-implant mucositis lesions at abutments with different
microstructures in humans. MATERIAL & METHODS: In a randomized, controlled,
interventional two-centre study, a total of 28 patients had received 28 target
implants and were randomly allocated to either partially microgrooved (test) or
machined (control) healing abutments. The study was accomplished in three phases,
including a wound healing period (WH) following implant placement (12 weeks), a
plaque exposure phase (EP-21 days) and a resolution phase (RP-16 weeks). Clinical
(e.g. bleeding on probing-BOP), immunological (MMP-8) and microbiological (DNA
counts for 11 species) parameters were evaluated. RESULTS: The incidence of peri
implant mucositis at EPd21 was comparable in both test and control groups (60.0%
versus 61.5%), but markedly lower at control abutments after a nonsurgical
treatment and reconstitution of oral hygiene measures at RPw16 (46.7% versus
15.4%). At any follow-up visit (i.e. EP and RP), clinical parameters, MMP-8
levels and DNA counts of major bacterial species were not significantly different
between both groups. CONCLUSION: The onset, progression and resolution of
experimental peri-implant mucositis lesions were comparable in both groups.
PMID- 29331022
TI - Open letter to journal editors on: International consensus radiochemistry
nomenclature guidelines.
PMID- 29331023
TI - Temozolomide analog PMX 465 downregulates MGMT expression in HCT116 colorectal
carcinoma cells.
AB - The efficacy of temozolomide (TMZ) treatment for cancers is currently limited by
inherent or the development of resistance, particularly, but not exclusively, due
to the expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase
(MGMT) in a significant proportion of tumors. We have found that TMZ analog C8
methyl imidazole tetrazine (PMX 465) displayed good anticancer activity against
the colorectal carcinoma HCT116 cells which are MGMT-overexpressing and mismatch
repair (MMR)-deficient. In this study, we found that PMX 465 could downregulate
the expression of MGMT in HCT116 cells at the protein and mRNA levels. We found
that PMX 465 could reduce MGMT expression by increasing the binding of wild-type
p53 to the MGMT promoter and reducing the binding of Sp1 to the MGMT promoter.
PMID- 29331025
TI - Multidimensional endotypes of chronic rhinosinusitis and their association with
treatment outcomes.
AB - BACKGROUND: The expression of chronic rhinosinusitis (CRS) is multidimensional.
Disease heterogeneity in patients with CRS remains poorly understood. This study
aimed to identify endotypes of CRS using cluster analysis by integrating
multidimensional characteristics and to explore their association with treatment
outcomes. METHODS: A total of 28 clinical variables and 39 mucosal cellular and
molecular variables were analyzed using principal component analysis. Cluster
analysis was performed on 246 prospectively recruited Chinese CRS patients with
at least 1-year postoperative follow-up. Difficult-to-treat CRS was characterized
in each generated cluster. RESULTS: Seven subject clusters were identified.
Cluster 1 (13.01%) was comparable to the classic well-defined eosinophilic CRS
with polyps, having severe disease and the highest proportion of difficult-to
treat CRS. Patients in cluster 2 (16.26%) and cluster 4 (13.82%) had relatively
lower proportions of presence of polyps and presented mild inflammation with
moderate proportions of difficult-to-treat cases. Subjects in cluster 2 were
highly atopic. Cluster 3 (7.31%) and cluster 6 (21.14%) were characterized by
severe or moderate neutrophilic inflammation, respectively, and with elevated
levels of IL-8 and high proportions of difficult-to-treat CRS. Cluster 5 (4.07%)
was a unique group characterized by the highest levels of IL-10 and lacked
difficult-to-treat cases. Cluster 7 (24.39%) demonstrated the lowest symptom
severity, a low proportion of difficult-to-treat CRS, and low inflammation load.
Finally, we found that difficult-to-treat CRS was associated with distinct
clinical features and biomarkers in the different clusters. CONCLUSIONS: Distinct
clinicopathobiologic clusters of CRS display differences in clinical response to
treatments and characteristics of difficult-to-treat CRS.
PMID- 29331024
TI - Combination therapy of lovastatin and AMP-activated protein kinase activator
improves mitochondrial and peroxisomal functions and clinical disease in
experimental autoimmune encephalomyelitis model.
AB - Recent studies report that loss and dysfunction of mitochondria and peroxisomes
contribute to the myelin and axonal damage in multiple sclerosis (MS). In this
study, we investigated the efficacy of a combination of lovastatin and AMP
activated protein kinase (AMPK) activator (AICAR) on the loss and dysfunction of
mitochondria and peroxisomes and myelin and axonal damage in spinal cords,
relative to the clinical disease symptoms, using a mouse model of experimental
autoimmune encephalomyelitis (EAE, a model for MS). We observed that lovastatin
and AICAR treatments individually provided partial protection of
mitochondria/peroxisomes and myelin/axons, and therefore partial attenuation of
clinical disease in EAE mice. However, treatment of EAE mice with the lovastatin
and AICAR combination provided greater protection of mitochondria/peroxisomes and
myelin/axons, and greater improvement in clinical disease compared with
individual drug treatments. In spinal cords of EAE mice, lovastatin-mediated
inhibition of RhoA and AICAR-mediated activation of AMPK cooperatively enhanced
the expression of the transcription factors and regulators (e.g. PPARalpha/beta,
SIRT-1, NRF-1, and TFAM) required for biogenesis and the functions of
mitochondria (e.g. OXPHOS, MnSOD) and peroxisomes (e.g. PMP70 and catalase). In
summary, these studies document that oral medication with a combination of
lovastatin and AICAR, which are individually known to have immunomodulatory
effects, provides potent protection and repair of inflammation-induced loss and
dysfunction of mitochondria and peroxisomes as well as myelin and axonal
abnormalities in EAE. As statins are known to provide protection in progressive
MS (Phase II study), these studies support that supplementation statin treatment
with an AMPK activator may provide greater efficacy against MS.
PMID- 29331027
TI - MiR-137 functions as a tumor suppressor in pancreatic cancer by targeting MRGBP.
AB - miRNAs are small noncoding RNAs that act as critical epigenetic regulators in
tumor carcinogenesis. In this study, our data showed that miR-137 was
significantly downregulated in 58 pairs of human pancreatic cancer (PanCa)
tissues and PanCa cell lines. Furthermore, the deregulated miR-137 was correlated
with increased tumor size, higher TNM stage, and worse prognosis in pancreatic
cancer. Functional studies demonstrated that overexpression of miR-137
dramatically suppressed cell proliferation and induced cell apoptosis in vitro.
Meanwhile, upregulated miR-137 remarkably inhibited migration and invasion of
pancreatic cancer cells. Further studies indicated that MRGBP was identified as
the direct downstream target gene of miR-137. In addition, MRGBP expression is
significantly downregulated in miR-137-transfected cells. Our previous study
revealed that silencing of MRGBP suppressed the growth of PanCa cells in vitro
and in vivo and also promoted apoptosis, and inhibited migration and invasion of
PanCa cells, which are consistent with the effects of miR-137 overexpression.
Taken together, our findings suggest that miR-137 may function as a novel tumor
promoter through directly targeting MRGBP in PanCa.
PMID- 29331026
TI - The asthma-rhinitis multimorbidity is associated with IgE polysensitization in
adolescents and adults.
AB - BACKGROUND: Children with multimorbid asthma and rhinitis show IgE
polysensitization to several allergen sources. This association remains poorly
studied in adolescents and adults using defined allergen molecules. We
investigated IgE sensitization patterns towards a broad panel of aeroallergen
components in adults and adolescents with a focus on individuals with asthma and
rhinitis multimorbidity. METHODS: IgE reactivity to 64 micro-arrayed aeroallergen
molecules was determined with the MeDALL-chip in samples from the French EGEA
study (n = 840, age = 40.7 +/- 17.1) and the Swedish population-based birth
cohort BAMSE (n = 786, age = 16 +/- 0.26). The age- and sex-adjusted associations
between the number of IgE-reactive allergen molecules (>=0.3 ISU) and the asthma
rhinitis phenotypes were assessed using a negative binomial model. RESULTS:
Groups representing 4 phenotypes were identified: no asthma-no rhinitis (A-R-;
30% in EGEA and 54% in BAMSE), asthma alone (A+R-; 11% and 8%), rhinitis alone (A
R+; 15% and 24%) and asthma-rhinitis (A+R+; 44% and 14%). The numbers of IgE
reactive aeroallergen molecules significantly differed between phenotypes (median
in A-R-, A+R-, A-R+ and A+R+: 0, 1, 2 and 7 in EGEA and 0, 0, 3 and 5 in BAMSE).
As compared to A-R- subjects, the adjusted ratio of the mean number of IgE
reactive molecules was higher in A+R+ than in A+R- or A-R+ (10.0, 5.4 and 5.0 in
EGEA and 7.2, 0.7 and 4.8 in BAMSE). CONCLUSION: The A+R+ phenotype combined the
sensitization pattern of both the A-R+ and A+R- phenotypes. This multimorbid
polysensitized phenotype seems to be generalizable to various ages and allergenic
environments and may be associated with specific mechanisms.
PMID- 29331028
TI - Alteration in microRNA-17-92 dynamics accounts for differential nature of
cellular proliferation.
AB - MicroRNAs associated with the mir-17-92 cluster are crucial regulators of the
mammalian cell cycle, as they inhibit transcription factors related to the E2F
family that tightly control decision-making events for a cell to commit for
active cellular proliferation. Intriguingly, in many solid cancers, these mir-17
92 cluster members are overexpressed, whereas in some hematopoietic cancers they
are down-regulated. Our proposed model of the Myc/E2F/mir-17-92 network
demonstrates that the differential expression pattern of mir-17-92 in different
cell types can be conceived due to having a contrasting E2F dynamics induced by
mir-17-92. The model predicts that by explicitly altering the mir-17-92-related
part of the network, experimentally it is possible to control cellular
proliferation in a cell type-dependent manner for therapeutic intervention.
PMID- 29331029
TI - Characterization of CD34+ hematopoietic cells in systemic mastocytosis: Potential
role in disease dissemination.
AB - BACKGROUND: Recent studies show that most systemic mastocytosis (SM) patients,
including indolent SM (ISM) with (ISMs+) and without skin lesions (ISMs-), carry
the KIT D816V mutation in PB leukocytes. We investigated the potential
association between the degree of involvement of BM hematopoiesis by the KIT
D816V mutation and the distribution of different maturation-associated
compartments of bone marrow (BM) and peripheral blood (PB) CD34+ hematopoietic
precursors (HPC) in ISM and identified the specific PB cell compartments that
carry this mutation. METHODS: The distribution of different maturation-associated
subsets of BM and PB CD34+ HPC from 64 newly diagnosed (KIT-mutated) ISM patients
and 14 healthy controls was analyzed by flow cytometry. In 18 patients, distinct
FACS-purified PB cell compartments were also investigated for the KIT mutation.
RESULTS: ISM patients showed higher percentages of both BM and PB MC-committed
CD34+ HPC vs controls, particularly among ISM cases with MC-restricted KIT
mutation (ISMMC ); this was associated with progressive blockade of maturation of
CD34+ HPC to the neutrophil lineage from ISMMC to multilineage KIT-mutated cases
(ISMML ). Regarding the frequency of KIT-mutated cases and cell populations in
PB, variable patterns were observed, the percentage of KIT-mutated PB CD34+ HPC,
eosinophils, neutrophils, monocytes and T cells increasing from ISMs-MC and
ISMs+MC to ISMML patients. CONCLUSION: The presence of the KIT D816V mutation in
PB of ISM patients is associated with (early) involvement of circulating CD34+
HPC and multiple myeloid cell subpopulations, KIT-mutated PB CD34+ HPC
potentially contributing to early dissemination of the disease.
PMID- 29331030
TI - Single-molecule nucleosome remodeling by INO80 and effects of histone tails.
AB - Genome maintenance and integrity requires continuous alterations of the
compaction state of the chromatin structure. Chromatin remodelers, among others
the INO80 complex, help organize chromatin by repositioning, reshaping, or
evicting nucleosomes. We report on INO80 nucleosome remodeling, assayed by single
molecule Foerster resonance energy transfer on canonical nucleosomes as well as
nucleosomes assembled from tailless histones. Nucleosome repositioning by INO80
is a processively catalyzed reaction. During the initiation of remodeling, probed
by the INO80 bound state, the nucleosome reveals structurally heterogeneous
states for tailless nucleosomes (in contrast to wild-type nucleosomes). We,
therefore, propose an altered energy landscape for the INO80-mediated nucleosome
sliding reaction in the absence of histone tails.
PMID- 29331031
TI - Comparative study of efficacy and safety between bladder body and trigonal
intravesical onabotulinumtoxina injection in the treatment of interstitial
cystitis refractory to conventional treatment-A prospective, randomized, clinical
trial.
AB - PURPOSE: Intravesical onabotulinumtoxinA (BoNT-A) injection can relieve symptoms
of interstitial cystitis/bladder pain syndrome (IC/BPS). However, the therapeutic
efficacy of different injection sites is not well known. This study compared
therapeutic efficacy and safety between bladder body and trigonal BoNT-A
injection. MATERIALS AND METHODS: Patients were randomly treated with 100U of
BoNT-A in 10 mL saline injected into 20 bladder body sites or 10 trigonal sites.
The primary endpoint was changes of Visual Analog Scale (VAS) for Pain at 8th
week after injection. Secondary endpoint included changes of Global Response
Assessment (GRA), urinary frequency episodes, O'Leary-Sant score (OSS), and
urodynamic study. RESULTS: Thirty-nine patients (bladder body, N = 20; trigone, N
= 19) completed the study visits. Patients in both group had significant
improvement in VAS, OSS, and functional bladder capacity after treatment. There
was no significant difference in changes of urinary frequency, voided volume,
post-void residual volume, and bladder capacity from baseline to 8 weeks between
groups. Thirteen (65.0%) patients in bladder body group and 10 (52.6%) patients
in trigone group had decrease of VAS more than 2 points after treatment (P =
0.43). Excellent symptom improvement (GRA >= 2) was noted in 9 (45%) patients
with bladder body injection and 10 (52.6%) patients with trigonal injection (P =
0.63). Nine (45.0%) patients in bladder body group and 10 (52.6%) in trigonal
group experienced dysuria after treatment (P = 0.52). CONCLUSION: No significant
difference in the improvement of IC symptoms and urodynamic parameters after
intravesical BoNT-A injection in the bladder body or trigone. The rate of adverse
events was similar between groups.
PMID- 29331032
TI - A split-body study evaluating the efficacy of a conformable surface cryolipolysis
applicator for the treatment of male pseudogynecomastia.
AB - BACKGROUND: Cryolipolysis is a non-invasive method of body shaping that has been
used for male pseudogynecomastia. However, traditional vacuum suction
cryolipolysis requires a minimum pinchable fat layer which may not always be
present in this area. OBJECTIVE: To evaluate the efficacy and safety of a
conformable surface cryolipolysis applicator for the reduction of male
pseudogynecomastia. MATERIALS AND METHODS: Ten male subjects with
pseudogynecomastia received two cycles of cryolipolysis to the breast 6 weeks
apart. Ultrasound was used to measure the thickness of adipose tissue. RESULTS:
Seven of 10 patients completed the study. Compared to baseline, the mean +/- SD
change in adipose tissue thickness was 8.12 +/- 6.94 mm for the treated versus
1.03 +/- 6.03 mm for the control breast at week 6 (p = 0.014), and 8.71 +/- 7.04
mm for the treated vs. 2.66 +/- 7.04 mm for the control breast at week 12 (P =
0.16). Four (4) of seven (57%) patients were at least slightly satisfied with the
treated breast, and although subject satisfaction was higher in the treated
breast, this did not reach significance (0.085). Adverse events were mild and
transient. CONCLUSION: A conformable surface cryolipolysis applicator was
effective in reducing the mean adipose tissue thickness in subjects with male
pseudogynecomastia. Lasers Surg. Med. (c) 2018 Wiley Periodicals, Inc.
PMID- 29331034
TI - Effects of in situ selenium exposure and maternal transfer on survival and
deformities of brown trout (Salmo trutta) fry.
AB - Offspring of wild adult brown trout exposed to a range of Se concentrations were
reared in a laboratory setting to primarily assess effects on survival and
deformities. Maternal whole-body Se concentrations ranged from 4.7 to 22.6 mg/kg
dry weight for wild fish. Corresponding Se concentrations in embryos ranged from
6.2 to 40.3 mg/kg dry weight. Significant relationships were found between embryo
and whole-body tissue concentrations. Increasing egg Se concentrations were
correlated with decreasing survival; however, hatch success was not significantly
correlated with increasing embryo Se. The best fit effect concentration, 10%
(EC10) for survival in the hatch to swim-up period was 20.6 mg/kg dry weight, and
the EC10 for hatch to test termination at 88 d was 20.5 mg/kg dry weight egg Se.
The best fit model for deformities was based on a baseline-adjusted severity
index and resulted in an EC10 of 21.8 mg/kg dry weight egg Se. Both the best fit
model EC10s represent more sensitive values than the published range of trout
species EC10s. An egg to whole-body tissue conversion factor derived from the
paired data resulted in a conversion factor for brown trout of 1.46, which
resulted in a whole-body tissue EC10 of 14.04 mg/kg dry weight at an egg tissue
EC10 of 20.5 mg/kg dry weight. Environ Toxicol Chem 2018;37:1396-1408. (c) 2018
SETAC.
PMID- 29331033
TI - The efficacy and safety comparison of surgical treatments for stress urinary
incontinence: A network meta-analysis.
AB - AIMS: Stress urinary incontinence (SUI) is a common problem worldwide. Mainstream
surgical procedures include tension-free vaginal tape (TVT), transobturator tape
(TOT), tension-free vaginal tape-obturator (TVT-O), tension-free vaginal tape
SECUR (TVT-S), and adjustable single-incision sling (Ajust). The aim of this
study was to compare the efficacy and safety of these surgical procedures and
assess which surgery is most optimal for SUI by adopting a network meta-analysis
(NMA). METHODS: Electronic databases including PubMed, Cochrance Library, and
Embase database were researched systematically, until March 21, 2017. The
randomized controlled trials (RCTs) that compared the efficacy and safety of TVT,
TOT, TVT-O, TVT-S, and Ajust were identified. The studies were included in the
analysis when met the predefined inclusion criteria. After demographic and
outcome data extraction, a network meta-analysis was conducted with software R
3.3.2 and STATA 14.0. Objective cure rate, subjective cure rate, postoperative
complication rate, bladder perforation, tape erosion, urinary retention, and
postoperative pain were considered as outcomes, and the outcomes were displayed
as odds ratios (ORs) and 95% credible intervals (CrI). The consistency of direct
and indirect evidence was assessed by node splitting. The ranks based on
probabilities of intervention for the different endpoints were performed.
RESULTS: Fourty-five RCTs with 7295 participants were analyzed. The NMA results
revealed that, TVT, TOT, and Ajust had a higher objective cure rate than TVT-O
and TVT-S (TVT-O: OR = 0.76, 95%CI [0.61, 0.94]; TVT-S: OR = 0.41, 95%CI [0.28,
0.60]). TVT, TOT, and TVT-O had a superior subjective cure rate than TVT-S and
Ajust (Ajust: OR = 0.45, 95%CI [0.20, 0.91]; TVT-S: OR = 0.29, 95%CI [0.15,
0.56]). With TVT as the reference, TVT-S had a statistically lower postoperative
complication rate (TVT-S: OR = 0.39, 95%CI [0.16, 0.89]). TVT-O, TVT-S, and TOT
had a significantly lower bladder perforation rate (TOT: OR = 0.076, 95%CI
[0.0060, 0.37]; TVT-O: OR = 4.1e-17, 95%CI [6.1e-48, 0.0032]; TVT-S: OR = 3.8e
17, 95%CI [1.8e-48, 0.0052]). There were no obvious differences between the five
treatments for tape erosion. TVT-O exhibited a less postoperative retention (TVT
O: OR = 0.35, 95%CI [0.16, 0.74]). Probabilities of ranking results indicated
that TOT was the treatment with best ranking in efficacy and a relatively high
safety. CONCLUSIONS: Our study recommend TOT as the optimal regimen for SUI with
high efficacy and moderate safety when compared with TVT, TVT-O, TVT-S, and Ajust
interventions. However, with the limitation of our study, additional high-quality
studies are needed to further evaluate the outcomes.
PMID- 29331035
TI - Noninvasive optical spectroscopy for identification of non-melanoma skin cancer:
Pilot study.
AB - OBJECTIVE: Optical spectroscopy offers a noninvasive alternative to biopsy as a
first-line screening tool for suspicious skin lesions. This study sought to
define several optical parameters across malignant and benign tissue types. STUDY
DESIGN: Prospective pilot trial utilizing the Zenalux IM1 optical spectroscopy
device from April 2016 to February 2017. For each skin lesion, provider pre
biopsy probability of malignancy was compared to histolopathologic diagnosis.
Optical data were characterized across basal cell carcinoma (BCC; n = 9),
squamous cell carcinoma (SCC; n = 5), actinic keratosis (AK; n = 4), scar tissue
(n = 6), nevus (n = 2), and neurofibroma (NF; n = 1). Across all patients,
agreement was determined between control measurements collected adjacent to the
lesion and from the upper extremity. METHODS: Prospective single center pilot
study. The optical properties of 27 cutaneous lesions were collected from 18
adult patients presenting to Otolaryngology and Dermatology clinics with
suspicious skin lesions warranting biopsy. Spectroscopy measurements were
recorded for each lesion: two at the lesion site, two at an adjacent site
(internal control), and one at the central medial upper extremity (arm control).
Variables of interest included absolute oxygenated hemoglobin (Hb), Hb
saturation, total Hb concentration, and Eumelanin concentration. For each lesion,
internal control averages were subtracted from lesion averages to provide delta
parameter values, and lesion averages were divided by internal control averages
to provide ratio parameter values. RESULTS: Mean percent difference between pre
biopsy probability of malignancy and histology was 29%, with a difference of 75%
or greater seen in 5 of 25 lesions. Mean values for BCC, SCC, AK, and scar tissue
varied most between extracted mean reduced scatter estimate (MUa'; cm- ) delta
values (BCC: -2.2 +/- 3.8; SCC: -3.9 +/- 2.0; AK: -3.3 +/- 4.2, Scar: -1.7 +/-
1.2) and total Hb (uM) ratio (BCC: 2.0 +/- 3.3; SCC: 3.0 +/- 1.3; AK: 1.1 +/-
0.6; Scar: 1.4 +/- 1.1). Agreement between local and arm controls was poor.
CONCLUSION: This pilot trial utilizes optical spectroscopy as a noninvasive
method for determining cutaneous lesion histology. Effect sizes observed across
optical parameters for benign and malignant tissue types will guide larger
prospective studies that may ultimately lead to prediction of lesional histology
without need for invasive biopsy. Lasers Surg. Med. 50:246-252, 2018. (c) 2018
Wiley Periodicals, Inc.
PMID- 29331036
TI - Prognostic significance of miR-21 and PDCD4 in patients with stage II esophageal
carcinoma after surgical resection.
AB - Many studies have shown that randomized clinical trial with long-term follow-up
found no improvement in stage II esophageal carcinoma (EC) patients receiving
preoperative neoadjuvant chemoradiotherapy or chemotherapy treatment, this
limitation underscored the urgent need for novel and reliable biomarkers for
prognosis and prediction in stage II EC. miR-21 is frequently over-expressed
while programmed cell death 4 (PDCD4) is often down-regulated in solid tumors.
This study aimed to investigate the clinicopathological and prognostic
significance of miR-21 and PDCD4 expression and to elucidate any correlation
between miR-21 and PDCD4 expression in stage II EC patients. The expression level
of miR-21 was up-regulated while the PDCD4 protein was down-regulated in stage II
EC tissues compared with the adjacent non-cancerous tissues. Analyses of the
clinicopathological parameters indicated that miR-21 expression was associated
with differentiation grade, T stage, and N stage. PDCD4 protein expression was
associated with T stage, N stage, and tumor size. The univariate linear
regression analysis suggested a significant negative correlation between miR-21
and PDCD4 expression. The Kaplan-Meier curve showed that high miR-21 expression
or low PDCD4 expression predicted poor progression-free survival (PFS) and
overall survival (OS) of patients with stag II EC. In conclusion, both up
regulated miR-21 and down-regulated PDCD4 expression were associated with the
aggressive progression and poor prognosis of stage II EC. miR-21 and PDCD4 might
be potential biomarkers of tumor progression and indicators of prognosis of stag
II EC.
PMID- 29331037
TI - Pharmacist Intervention for Blood Pressure Control in Patients with Diabetes
and/or Chronic Kidney Disease.
AB - OBJECTIVES: The objectives of this study were to determine if hypertensive
patients with comorbid diabetes mellitus (DM) and/or chronic kidney disease (CKD)
receiving a pharmacist intervention had a greater reduction in mean blood
pressure (BP) and improved BP control at 9 months compared with those receiving
usual care; and compare Seventh Report of the Joint National Committee on
Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7)
guideline and 2014 guideline (JNC 8) BP control rates in patients with DM and/or
CKD. METHODS: This cluster randomized trial included 32 medical offices in 15
states. Clinical pharmacists made treatment recommendations to physicians at
intervention sites. This post hoc analysis evaluated mean BP and BP control rates
in the intervention and control groups. MAIN RESULTS: The study included 335
patients (227 intervention, 108 control) when mean BP and control rates were
evaluated by JNC 7 inclusion and control criteria. When JNC 8 inclusion and
control criteria were applied, 241 patients (165 intervention, 76 control)
remained and were included in the analysis. The pharmacist-intervention group had
significantly greater mean systolic blood pressure reduction compared with usual
care at 9 months (8.64 mm Hg; 95% confidence interval [CI] -12.8 to -4.49,
p<0.001). The pharmacist-intervention group had significantly higher BP control
at 9 months than usual care by either the JNC 7 or JNC 8 inclusion and control
groups (adjusted odds ratio [OR] 1.97, 95% CI 1.01-3.86, p=0.0470 and OR 2.16,
95% CI 1.21-3.85, p=0.0102, respectively). PRINCIPAL CONCLUSIONS: This study
demonstrated that a physician-pharmacist collaborative intervention was effective
in reducing mean systolic BP and improving BP control in patients with
uncontrolled hypertension with DM and/or CKD, regardless of which BP guidelines
were used.
PMID- 29331038
TI - Modeling strategic sperm allocation: Tailoring the predictions to the species.
AB - Two major challenges exist when empirically testing the predictions of sperm
allocation theory. First, the study species must adhere to the assumptions of the
model being tested. Unfortunately, the common assumption of sperm allocation
models that females mate a maximum of once or twice does not hold for many, if
not most, multiply and sequentially mating animals. Second, a model's parameters,
which dictate its predictions, must be measured in the study species. Common
examples of such parameters, female mating frequency and sperm precedence
patterns, are unknown for many species used in empirical tests. Here, we present
a broadly applicable model, appropriate for multiply, sequentially mating
animals, and test it in three species for which data on all the relevant
parameter values are available. The model predicts that relative allocation to
virgin females, compared to nonvirgins, depends on the interaction between female
mating rate and the sperm precedence pattern: relative allocation to virgins
increases with female mating rate under first-male precedence, while the opposite
is true under later-male precedence. Our model is moderately successful in
predicting actual allocation patterns in the three species, including a cricket
in which we measured the parameter values and performed an empirical test of
allocation.
PMID- 29331039
TI - Expression of chemerin in the synovial fluid of patients with temporomandibular
joint disorders.
AB - The synovial membrane and fluid are significantly involved in the pathogenesis of
temporomandibular joint (TMJ) disorders. This study aimed to investigate the
relation between levels of chemerin in the synovial fluid (SF) of patients with
TMJ disorder and their relationship. Sixty samples of SF were obtained from
patients with an internal derangement (ID) or osteoarthritis (OA). Chemerin in
the SF was examined by enzyme-linked immunosorbent assay (ELISA). The results
showed greater levels of chemerin in the SF of patients with OA than ID. While
chemerin levels were positively correlated with pain scores, they were inversely
correlated with MMO. Chemerin levels increased progressively as the disorder
stage became more severe. The findings of this study suggest that chemerin in SF
may play role as a predisposing factor and may represent a novel potential
prognostic biochemical marker in the pathogenesis of TMJ disorders.
PMID- 29331040
TI - Jun, Gal, Cd74, and C1qb as potential indicator for neuropathic pain.
AB - Neuropathic pain is a kind of pain caused by primary or secondary impairment or
dysfunction of peripheral or central nervous system. Patients with neuropathic
pain were often with poor clinical outcome. We screened the differentially
expressed genes between sciatic nerve injury and dorsal root ganglion gene in the
sham operation model. Microarray and the spared nerve injury module were used to
explore the molecular mechanism of neuropathic pain by injuries and the
differentially expressed genes (DEGs) were identified out. Besides, the
bioinformatics methods were used to figure out the signaling pathways and
expression regulation pattern these DEGs were enriched in, which may provide a
basis for the molecular research and medicine target of therapy. Besides, protein
protein interaction network analysis was performed on these selected intersection
genes. A total of 40 DEGs were screened out and only pctp gene was down
regulated, the left 39 genes were all up-regulated. Then, GO and KEGG enrichment
analysis were performed on these intersection genes by DAVID software.
Furthermore, protein-protein interaction network analysis was used to analyze the
critical genes of neuropathic pain. Finally, four genes, that is, Jun, Gal, Cd74,
and C1qb were identified to have strong interactions with other genes, which may
function as the prognostic and predictive genes of neuropathic pain caused by
peripheral injuries. Our results suggested that four differentially expressed
genes, Jun, Gal, Cd74, and C1qb, had the potential to serve as prognostic or
predictive markers for neuropathic pain, suggesting a potential application in
the improvement of prognostic tools and treatments.
PMID- 29331041
TI - Effect of low-level laser therapy on the healing of sites grafted with coagulum,
deproteinized bovine bone, and biphasic ceramic made of hydroxyapatite and beta
tricalcium phosphate. In vivo study in rats.
AB - OBJECTIVE: The aim of this study was to evaluate the effect of low-level laser
therapy (LLLT) on the healing of biomaterial graft areas (i.e., coagulum,
deproteinized bovine bone, and biphasic ceramics comprising hydroxyapatite and
beta-tricalcium phosphate). MATERIAL AND METHODS: Ninety rats were divided into
two groups according to laser irradiation use (lambda 808 nm, 100 mW, phi ~600
MUm, seven sessions with 28 J of irradiation dose in total): a laser group and a
control group. Each of these groups was divided into three subgroups of 15
animals each according to the type of biomaterial used: Coagulum (COA),
deproteinized bovine bone (DBB), and hydroxyapatite/beta-tricalcium phosphate
(HA/betaTCP). Biomaterials were inserted into Teflon domes, and these domes were
grafted to the lateral aspect of the mandibular branch of the rats. The animals
were sacrificed after 30, 60, and 90 days. Scarring patterns were evaluated by
microtomography and histometry. The expression levels of BMP2, osteocalcin (OCN),
and alkaline phosphatase (ALP) were evaluated by immunohistochemistry. The mRNA
expression levels of ALP, BMP2, Jagged1, Osterix, Runx2, and TGFbeta1 were
determined by RT-qPCR. RESULTS: The animals treated with LLLT exhibited increased
mineralized tissues and bone, particularly after 90 days. These increases were
associated with increased BMP2, OCN, and ALP protein expression and ALP, BMP2,
and Jagged1 mRNA expression. CONCLUSION: LLLT improved the osteoconductive
potential of DBB and HA/betaTCP grafts and bone formation in ungrafted areas.
Lasers Surg. Med. (c) 2018 Wiley Periodicals, Inc.
PMID- 29331042
TI - The effects of social context and food abundance on chimpanzee feeding
competition.
AB - Feeding competition is thought to play a role in primate social organization as
well as cognitive evolution. For chimpanzees (Pan troglodytes), social and
ecological factors can affect competition, yet how these factors interact to
affect feeding behavior is not fully understood; they can be difficult to
disentangle in wild settings. This experiment investigated the differential
effects of food quantity, the presence of a co-feeding partner, and the
contestability of a food patch on feeding rate. We presented tolerant pairs of
chimpanzees from a semi-captive social group with an apparatus comprising a
matrix of transparent tubes between two adjacent rooms, of which, either all
(abundant condition) or only a small proportion (scarce condition) were baited
with peanuts. Dyads were either grouped into the competitive treatment, in which
peanuts were accessible from both sides of the apparatus simultaneously, or the
non-competitive treatment, in which the peanuts were pre-divided; half of the
tubes were accessible to one chimpanzee from one side, and the other half were
accessible only from the opposite side of the apparatus. We compared dyadic
tolerance levels with individual feeding rates across quantity conditions and
between competitive treatments. While tolerance and food quantity had no effect
on feeding rate, partner presence significantly increased feeding rate relative
to individual feeding. This increase was much larger when the dyads directly
competed over the peanuts than when they were co-feeding on a pre-divided set of
peanuts. Thus, in a co-feeding situation, the presence of another individual and,
to an even larger extent, the contestability of the food source play a larger
role in chimpanzee feeding behavior than dyadic tolerance or food quantity. These
findings highlight the relative impact of social facilitation and direct
competition on co-feeding behavior between pairs of chimpanzees.
PMID- 29331043
TI - Role of miR-203 in estrogen receptor-mediated signaling in the rat uterus and
endometrial carcinoma.
AB - The role of microRNAs (miRNA) in estrogen receptor (ER) signaling in the uterus
and in endometrial cancer is not well understood. We therefore analyzed miRNA
expression in uterine samples from a standard 3-day uterotrophic assay using
young female adult rats to identify E2-regulated miRNAs. Microarray analysis
identified 47 E2 down-regulated miRNAs including miR-30a, and 25 E2up-regulated
miRNAs including miR-672, miR-203, and miR-146b. The strongly E2-upregulated miR
203 was selected for further analysis. miR-203 was deleted in the rat endometrial
adenocarcinoma cell line, RUCA-I, using CRISPR/CAS9. Five clones devoid of miR
203 expression were generated. Proliferation was reduced and G2-arrest was
observed in all miR-203 deficient RUCA-I clones. Transfection with a miR-203-3p
mimic partially rescues this effect. Comparison of mRNA expression in three miR
203 knockout clones to wild type RUCA-I cells reveals 566 miR-203-upregulated and
592 miR-203-downregulated genes. 43 of the genes that are upregulated by miR-203
knockout in vitro are downregulated in the uterus by E2. Of these Acer2, Zbtb20,
Ptn, Rcbtb2, Mum1l1, Hmgn3, and Nfat5 possess one or more seed sequence matches
in their 3'-UTR that are predicted to be targets of miR-203. These data
demonstrate the importance of E2 regulated miRNAs in general, and miR-203 in
particular, for E2 regulated gene expression and physiological processes
including proliferation and cell migration, in the uterus as well as in the
etiology of endometrial carcinomas.
PMID- 29331044
TI - Journey of oocyte from metaphase-I to metaphase-II stage in mammals.
AB - In mammals, journey from metaphase-I (M-I) to metaphase-II (M-II) is important
since oocyte extrude first polar body (PB-I) and gets converted into haploid
gamete. The molecular and cellular changes associated with meiotic cell cycle
progression from M-I to M-II stage and extrusion of PB-I remain ill understood.
Several factors drive oocyte meiosis from M-I to M-II stage. The mitogen
activated protein kinase3/1 (MAPK3/1), signal molecules and Rho family GTPases
act through various pathways to drive cell cycle progression from M-I to M-II
stage. The down regulation of MOS/MEK/MAPK3/1 pathway results in the activation
of anaphase-promoting complex/cyclosome (APC/C). The active APC/C destabilizes
maturation promoting factor (MPF) and induces meiotic resumption. Several signal
molecules such as, c-Jun N-terminal kinase (JNK2), SENP3, mitotic kinesin-like
protein 2 (MKlp2), regulator of G-protein signaling (RGS2), Epsin2, polo-like
kinase 1 (Plk1) are directly or indirectly involved in chromosomal segregation.
Rho family GTPase is another enzyme that along with cell division cycle (Cdc42)
to form actomyosin contractile ring required for chromosomal segregation. In the
presence of origin recognition complex (ORC4), eccentrically localized haploid
set of chromosomes trigger cortex differentiation and determine the division site
for polar body formation. The actomyosin contractile activity at the site of
division plane helps to form cytokinetic furrow that results in the formation and
extrusion of PB-I. Indeed, oocyte journey from M-I to M-II stage is coordinated
by several factors and pathways that enable oocyte to extrude PB-I. Quality of
oocyte directly impact fertilization rate, early embryonic development, and
reproductive outcome in mammals.
PMID- 29331045
TI - The urgent need for a harmonized severity scoring system for acute allergic
reactions.
AB - The accurate assessment and communication of the severity of acute allergic
reactions are important to patients, clinicians, researchers, the food industry,
and public health and regulatory authorities. Severity has different meanings to
different stakeholders with patients and clinicians rating the significance of
particular symptoms very differently. Many severity scoring systems have been
generated, most focusing on the severity of reactions following exposure to a
limited group of allergens. They are heterogeneous in format, none has used an
accepted developmental approach, and none has been validated. Their wide range of
outcome formats has led to difficulties with interpretation and application.
Therefore, there is a persisting need for an appropriately developed and
validated severity scoring system for allergic reactions that work across the
range of allergenic triggers and address the needs of different stakeholder
groups. We propose a novel approach to develop and then validate a harmonized
scoring system for acute allergic reactions, based on a data-driven method that
is informed by clinical and patient experience and other stakeholders'
perspectives. We envisage two formats: (i) a numerical score giving a continuum
from mild to severe reactions that are clinically meaningful and are useful for
allergy healthcare professionals and researchers, and (ii) a three-grade-based
ordinal format that is simple enough to be used and understood by other
professionals and patients. Testing of reliability and validity of the new
approach in a range of settings and populations will allow eventual
implementation of a standardized scoring system in clinical studies and routine
practice.
PMID- 29331047
TI - The economic burden of overactive bladder in the United States: A systematic
literature review.
AB - AIMS: Overactive bladder (OAB) affects up to 17% of the United States (US)
population. This study aimed to synthesize estimates of direct and indirect costs
of OAB in the US and compare costs among those with and without OAB. METHODS: A
systematic review was performed using MEDLINE/PubMed and Embase, from 2003 to
2016, following PRISMA guidelines. The target population was adults with
idiopathic OAB or urge urinary incontinence from the US. Data were extracted on
study and patient characteristics, all-cause and OAB-specific direct costs,
resource use, and indirect costs. Costs were inflated to a common price year of
2016 USD. RESULTS: Eighteen studies were included. Mean insurer paid all-cause
total direct healthcare costs ranged from 8168 to 15 569 USD, and OAB-specific
costs ranged from 656 to 860 USD per-patient annually. Estimates of the
incremental costs for OAB patients compared to non-OAB comparators ranged from
43% to 117%. One study estimated total annual indirect costs of OAB at 11 134 USD
per-patient. CONCLUSIONS: The range of direct healthcare costs reported for
managing patients with OAB varied, but was relatively small given the differing
contributing data sources, study designs, and cost definitions. Direct costs were
consistently higher among patients with OAB versus non-OAB comparisons, from a
1.4- to >2-fold increase annually. OAB-specific costs made up a small proportion
of all-cause costs, highlighting the clinical and economic impact of OAB-related
conditions such as falls, urinary tract infection, and depression. Few studies
were identified that examined the indirect costs of OAB in the US.
PMID- 29331046
TI - Prevalence, severity, and risk factors for acute exacerbations of nasal and sinus
symptoms by chronic rhinosinusitis status.
AB - BACKGROUND: Nasal and sinus symptoms (NSS) are common to many health conditions,
including chronic rhinosinusitis (CRS). Few studies have investigated the
occurrence and severity of, and risk factors for, acute exacerbations of NSS
(AENSS) by CRS status (current, past, or never met European Position Paper on
Rhinosinusitis [EPOS] criteria for CRS). METHODS: Four seasonal questionnaires
were mailed to a stratified random sample of Geisinger primary care patients.
Logistic regression was used to identify individual characteristics associated
with AENSS occurrence and severity by CRS status (current long-term, current
recent, past, never) using EPOS subjective symptoms-only (EPOSS ) CRS criteria.
We operationalized 3 AENSS definitions based on prescribed antibiotics or oral
corticosteroids, symptoms, and symptoms with purulence. RESULTS: Baseline and at
least 1 follow-up questionnaires were available from 4736 subjects. Self-reported
NSS severity with exacerbation was worst in the current long-term CRS group.
AENSS was common in all subgroups examined and generally more common among those
with current EPOSS CRS. Seasonal prevalence of AENSS differed by AENSS definition
and CRS status. Associations of risk factors with AENSS differed by definition,
but CRS status, body mass index, asthma, hay fever, sinus surgery history, and
winter season consistently predicted AENSS. CONCLUSIONS: In this first
longitudinal, population-based study of 3 AENSS definitions, NSS and AENSS were
both common, sometimes severe, and differed by EPOSS CRS status. Contrasting
associations of risk factors for AENSS by the different definitions suggest a
need for a standardized approach to definition of AENSS.
PMID- 29331048
TI - Dog bites in a U.S. county: age, body part and breed in paediatric dog bites.
AB - AIM: To compare characteristics of gender, age, body part and breed in dog bites.
METHODS: We reviewed 14 956 dog bites (4195 paediatric) reported to the Allegheny
County Health Department, USA, between 2007 and 2015. Using predefined age
groups, we performed linear regression to assess for subject age and bite
frequency and used binary logistic regression to evaluate for differences in
gender and body part. We used chi-squared test with Bonferroni correction to
evaluate for differences in reported breeds with age. RESULTS: There was a
negative correlation (-0.80, r2 = 0.64) between age and bite frequency. Children
0-3 years had a higher odds ratio (OR) of bites to the face [21.12, 95%
confidence interval (CI): 17.61-25.33] and a lower OR of bites to the upper (OR:
0.14, 95% CI: 0.12-0.18) and lower (OR: 0.19, 95% CI: 0.14-0.27) extremities.
'Pit bulls' accounted for 27.2% of dog bites and were more common in children 13
18 years (p < 0.01). Shih-Tzu bites were more common in children three years of
age and younger (p < 0.01). CONCLUSION: Dog bites occur with higher frequency at
younger ages, and head and neck injuries are more common in younger children. Pit
bull bites are more common in adolescents and Shih-Tzu bites more common in
younger children.
PMID- 29331049
TI - Prenatal maternal psychosocial stress and offspring's asthma and allergic
disease: A systematic review and meta-analysis.
AB - BACKGROUND: Prenatal maternal stress may influence offspring's atopic risk
through sustained cortisol secretion resulting from activation of the
hypothalamic-pituitary axis (HPA), leading to Th2-biased cell differentiation in
the foetus. We undertook a systematic review and meta-analysis investigating the
relationship between prenatal maternal psychosocial stress and risk of asthma and
allergy in the offspring. METHODS: We searched 11 electronic databases from 1960
to 2016, searched the grey literature and contacted experts in the field. Type of
stress indicator included mood disorders, anxiety, exposure to violence,
bereavement and socio-economic problems occurring during pregnancy, both
objectively and subjectively measured. We included all possible asthma and IgE
mediated allergy outcomes. We conducted random-effects meta-analyses to
synthesize the data. RESULTS: We identified 9779 papers of which 30 studies
(enrolling >6 million participants) satisfied inclusion criteria. The quality of
25 studies was moderate, 4 were strong, and one was weak. Maternal exposure to
any type of stressors was associated with an increased risk of offspring atopic
eczema/dermatitis (OR 1.34, 95% CI 1.22-1.47), allergic rhinitis (OR 1.30, 95% CI
1.04-1.62), wheeze (OR 1.34, 95% CI 1.16-1.54) and asthma (OR 1.15, 95% CI 1.04
1.27). Exposure to anxiety and depression had strongest effect compared to other
stressors. Exposure during the third trimester had the greatest impact compared
to first and second trimesters. The increased risk was stronger for early-onset
and persistent than for late-onset wheeze. Bereavement of a child (HR 1.28, 95%
CI 1.10-1.48) or a spouse (HR 1.40, 95% CI 1.03-1.90) increased the risk of
offspring asthma. CONCLUSIONS: Exposure to prenatal maternal psychosocial stress
was associated with increased risk, albeit modestly, of asthma and allergy in the
offspring. The pronounced risk during the third trimester may represent
cumulative stress exposure throughout pregnancy rather than trimester-specific
effect. Our findings may represent a causal effect or a result of inherent biases
in studies, particularly residual confounding.
PMID- 29331050
TI - Exercise counteracts lipotoxicity by improving lipid turnover and lipid droplet
quality.
AB - The incidence of obesity and metabolic disease, such as type 2 diabetes mellitus
(T2D), is rising globally. Dietary lipid over supply leads to lipid accumulation
at ectopic sites, such as skeletal muscle. Ectopic lipid storage is highly
correlated with insulin resistance and T2D, likely due to a loss of metabolic
flexibility - the capacity to switch between fat and glucose oxidation upon
insulin stimulation - and cellular dysfunction because of lipotoxicity. However,
muscle lipid levels are also elevated in endurance-trained athletes, presenting a
paradoxical phenotype of increased intramuscular lipids along with high insulin
sensitivity - the 'athletes' paradox'. This review focuses on recent human data
to characterize intramuscular lipid species in order to elucidate some of the
underlying mechanisms driving skeletal muscle lipotoxicity. There is evidence
that lipotoxicity is characterized by an increase in bioactive lipid species,
such as ceramide. The athletes' paradox supports the notion that regular physical
exercise has health benefits that might originate from the alleviation of
lipotoxicity. Indeed, exercise training alleviates intramuscular ceramide content
in obese individuals without a necessary decrease in ectopic lipid storage.
Furthermore, evidence shows that exercise training elevates markers of lipid
droplet dynamics such as the PLIN proteins, and triglyceride lipases ATGL and
HSL, as well as mitochondrial efficiency, potentially explaining the improved
lipid turnover and a reduction in the accumulation of lipotoxic intermediates
observed with the athelets' paradox.
PMID- 29331051
TI - Fecal incontinence knowledge, attitudes, and help-seeking behaviors among
community-dwelling adults in Korea.
AB - OBJECTIVES: Fecal incontinence (FI) is a common debilitating disorder that tends
to be underreported. Although low health literacy likely contributes to the
underreporting, studies on FI knowledge among the general population remain
scarce. We investigated how FI knowledge is associated with attitudes and help
seeking behaviors. METHODS: We conducted a cross-sectional survey among community
dwelling adults undergoing national health screening in Korea. A structured, self
administered questionnaire was used to assess FI knowledge, attitudes, and help
seeking behaviors. Odds ratios (ORs; 95% confidence intervals, CIs) were
estimated using logistic regression with adjustment for covariables. RESULTS: Of
the 601 participants completing the survey, only 29.8% were aware of the term FI,
and their knowledge levels were insufficient. As for FI-related attitudes, 24.6%
considered FI to be very rare, and 22.3% considered it to be moderately or less
distressing. Individuals who knew the term FI tended to consider FI more common
(OR: 2.45; 95%CI: 1.49-4.02) and distressing (OR: 1.68; 95%CI: 1.07-2.63) than
those without knowledge. Assuming future FI occurrence, those considering FI to
be distressing were less willing to ignore or self-manage the condition (OR:
0.25; 95%CI: 0.11-0.58). Among patients with FI (n = 83), only 30.1% had sought
help and 8.4% had consulted doctors. Knowing the term FI was significantly
associated with overall help-seeking behavior (OR: 9.23; 95%CI: 2.09-40.77).
CONCLUSIONS: FI knowledge levels and help-seeking rates were low among community
dwelling adults. FI knowledge was significantly associated with attitudes and
help-seeking behaviors. Future public education programs are warranted to improve
FI knowledge, attitudes, and help-seeking behaviors.
PMID- 29331052
TI - Flow pattern analysis in type B aortic dissection patients after stent-grafting
repair: Comparison between complete and incomplete false lumen thrombosis.
AB - Endovascular stent graft repair has become a common treatment for complicated
Stanford type B aortic dissection to restore true lumen flow and induce false
lumen thrombosis. Using computational fluid dynamics, this study reports the
differences in flow patterns and wall shear stress distribution in complicated
Stanford type B aortic dissection patients after endovascular stent graft repair.
Five patients were included in this study: 2 have more than 80% false lumen
thrombosis (group 1), while 3 others had less than 80% false lumen thrombosis
(group 2) within 1 year following endovascular repair. Group 1 patients had
concentrated re-entry tears around the abdominal branches only, while group 2
patients had re-entry tears that spread along the dissection line. Blood flow
inside the false lumen which affected thrombus formation increased with the
number of re-entry tears and when only small amounts of blood that entered the
false lumen exited through the branches. In those cases where dissection extended
below the abdominal branches (group 2), patients with fewer re-entry tears and
longer distance between the tears had low wall shear stress contributing to
thrombosis. This work provides an insight into predicting the development of
complete or incomplete false lumen thrombosis and has implications for patient
selection for treatment.
PMID- 29331054
TI - ARTIST: A fully automated artifact rejection algorithm for single-pulse TMS-EEG
data.
AB - Concurrent single-pulse TMS-EEG (spTMS-EEG) is an emerging noninvasive tool for
probing causal brain dynamics in humans. However, in addition to the common
artifacts in standard EEG data, spTMS-EEG data suffer from enormous stimulation
induced artifacts, posing significant challenges to the extraction of neural
information. Typically, neural signals are analyzed after a manual time-intensive
and often subjective process of artifact rejection. Here we describe a fully
automated algorithm for spTMS-EEG artifact rejection. A key step of this
algorithm is to decompose the spTMS-EEG data into statistically independent
components (ICs), and then train a pattern classifier to automatically identify
artifact components based on knowledge of the spatio-temporal profile of both
neural and artefactual activities. The autocleaned and hand-cleaned data yield
qualitatively similar group evoked potential waveforms. The algorithm achieves a
95% IC classification accuracy referenced to expert artifact rejection
performance, and does so across a large number of spTMS-EEG data sets (n = 90
stimulation sites), retains high accuracy across stimulation
sites/subjects/populations/montages, and outperforms current automated
algorithms. Moreover, the algorithm was superior to the artifact rejection
performance of relatively novice individuals, who would be the likely users of
spTMS-EEG as the technique becomes more broadly disseminated. In summary, our
algorithm provides an automated, fast, objective, and accurate method for
cleaning spTMS-EEG data, which can increase the utility of TMS-EEG in both
clinical and basic neuroscience settings.
PMID- 29331053
TI - REnal Flow and Microstructure AnisotroPy (REFMAP) MRI in Normal and Peritumoral
Renal Tissue.
AB - BACKGROUND: Diffusion-weighted imaging (DWI) provides insight into the
pathophysiology underlying renal dysfunction. Variants of DWI include intravoxel
incoherent motion (IVIM), which differentiates between microstructural diffusion
and vascular or tubular flow, and diffusion tensor imaging (DTI), which
quantifies diffusion directionality. PURPOSE: To investigate the reproducibility
of joint IVIM-DTI and compare controls to presurgical renal mass patients. STUDY
TYPE: Prospective cross-sectional. SUBJECTS: Thirteen healthy controls and ten
presurgical renal mass patients were scanned. Ten controls were scanned twice to
investigate reproducibility. FIELD STRENGTH/SEQUENCE: Subjects were scanned on a
3T system using 10 b-values and 20 diffusion directions for IVIM-DTI in a study
approved by the local Institutional Review Board. ASSESSMENT: Retrospective
coregistration and measurement of joint IVIM-DTI parameters were performed.
STATISTICAL ANALYSIS: Parameter reproducibility was defined as intraclass
correlation coefficient (ICC) >0.7 and coefficient of variation (CV) <30%.
Patient data were stratified by lesion side (contralateral/ipsilateral) for
comparison with controls. Corticomedullary differentiation was evaluated.
RESULTS: In controls, the reproducible subset of REnal Flow and Microstructure
AnisotroPy (REFMAP) parameters had average ICC = 0.82 and CV = 7.5%. In renal
mass patients, medullary fractional anisotropy (FA) was significantly lower than
in controls (0.227 +/- 0.072 vs. 0.291 +/- 0.044, P = 0.016 for the kidney
contralateral to the mass and 0.228 +/- 0.070 vs. 0.291 +/- 0.044, P = 0.018 for
the kidney ipsilateral). In the kidney ipsilateral to the mass, cortical
Dp,radial was significantly higher than in controls (P = 0.012). Conversely,
medullary Dp,axial was significantly lower in contralateral than ipsilateral
kidneys (P = 0.027) and normal controls (P = 0.044). DATA CONCLUSION: REFMAP-MRI
parameters provide unique information regarding renal dysfunction. In presurgical
renal mass patients, directional flow changes were noted that were not identified
with IVIM analysis alone. Both contralateral and ipsilateral kidneys in patients
show reductions in structural diffusivities and anisotropy, while flow metrics
showed opposing changes in contralateral vs. ipsilateral kidneys. LEVEL OF
EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.
PMID- 29331055
TI - The challenges and possibilities of public access defibrillation.
AB - Out-of-hospital cardiac arrest (OHCA) is a major health problem that affects
approximately four hundred and thousand patients annually in the United States
alone. It is a major challenge for the emergency medical system as decreased
survival rates are directly proportional to the time delay from collapse to
defibrillation. Historically, defibrillation has only been performed by
physicians and in-hospital. With the development of automated external
defibrillators (AEDs), rapid defibrillation by nonmedical professionals and
subsequently by trained or untrained lay bystanders has become possible. Much
hope has been put to the concept of Public Access Defibrillation with a massive
dissemination of public available AEDs throughout most Western countries.
Accordingly, current guidelines recommend that AEDs should be deployed in places
with a high likelihood of OHCA. Despite these efforts, AED use is in most
settings anecdotal with little effect on overall OHCA survival. The major reasons
for low use of public AEDs are that most OHCAs take place outside high incidence
sites of cardiac arrest and that most OHCAs take place in residential settings,
currently defined as not suitable for Public Access Defibrillation. However, the
use of new technology for identification and recruitment of lay bystanders and
nearby AEDs to the scene of the cardiac arrest as well as new methods for
strategic AED placement redefines and challenges the current concept and
definitions of Public Access Defibrillation. Existing evidence of Public Access
Defibrillation and knowledge gaps and future directions to improve outcomes for
OHCA are discussed. In addition, a new definition of the different levels of
Public Access Defibrillation is offered as well as new strategies for increasing
AED use in the society.
PMID- 29331056
TI - Exploring the advantages of multiband fMRI with simultaneous EEG to investigate
coupling between gamma frequency neural activity and the BOLD response in humans.
AB - We established an optimal combination of EEG recording during sparse multiband
(MB) fMRI that preserves high-resolution, whole-brain fMRI coverage while
enabling broad-band EEG recordings which are uncorrupted by MRI gradient
artefacts (GAs). We first determined the safety of simultaneous EEG recording
during MB fMRI. Application of MB factor = 4 produced <1 degrees C peak heating
of electrode/hardware during 20 min of GE-EPI data acquisition. However, higher
SAR sequences require specific safety testing, with greater heating observed
using PCASL with MB factor = 4. Heating was greatest in the electrocardiogram
channel, likely due to it possessing longest lead length. We investigated the
effect of MB factor on the temporal signal-to-noise ratio for a range of GE-EPI
sequences (varying MB factor and temporal interval between slice acquisitions).
We found that, for our experimental purpose, the optimal acquisition was achieved
with MB factor = 3, 3mm isotropic voxels, and 33 slices providing whole head
coverage. This sequence afforded a 2.25 s duration quiet period (without GAs) in
every 3 s TR. Using this sequence, we demonstrated the ability to record gamma
frequency (55-80 Hz) EEG oscillations, in response to right index finger
abduction, that are usually obscured by GAs during continuous fMRI data
acquisition. In this novel application of EEG-MB fMRI to a motor task, we
observed a positive correlation between gamma and BOLD responses in bilateral
motor regions. These findings support and extend previous work regarding coupling
between neural and hemodynamic measures of brain activity in humans and showcase
the utility of EEG-MB fMRI for future investigations.
PMID- 29331058
TI - Endoscopic band ligation for colonic diverticular bleeding.
PMID- 29331059
TI - Neuroanatomical correlates of grit: Growth mindset mediates the association
between gray matter structure and trait grit in late adolescence.
AB - There is a long-standing interest in exploring the factors related to student
achievement. As a newly explored personality trait, grit is defined as a person's
tendency to pursue long-term goals with continual perseverance and passion, and
grit plays a critical role in student achievement. Increasing evidence has shown
that growth mindset, the belief that one's basic abilities are malleable and can
be developed through effort, is a potential factor for cultivating grit. However,
less is known about the association between grit and the brain and the role of
growth mindset in this association. Here, we utilized voxel-based morphometry to
examine the neuroanatomical correlates of grit in 231 healthy adolescent students
by performing structural magnetic resonance imaging. The whole-brain regression
analyses revealed that the regional gray matter volume (rGMV) in the left
dorsolateral prefrontal cortex (DLPFC) negatively predicted grit. In contrast,
the rGMV in the right putamen positively predicted grit. Furthermore, mediating
analyses suggested that growth mindset served as a mediator in the association
between left DLPFC volume and grit. Our results persisted even after controlling
for the influences of self-control and delayed gratification. Overall, our study
presents novel evidence for the neuroanatomical basis of grit and highlights that
growth mindset might play an essential role in cultivating a student's grit
level.
PMID- 29331060
TI - Regional hippocampal vulnerability in early multiple sclerosis: Dynamic
pathological spreading from dentate gyrus to CA1.
AB - BACKGROUND: Whether hippocampal subfields are differentially vulnerable at the
earliest stages of multiple sclerosis (MS) and how this impacts memory
performance is a current topic of debate. METHOD: We prospectively included 56
persons with clinically isolated syndrome (CIS) suggestive of MS in a 1-year
longitudinal study, together with 55 matched healthy controls at baseline.
Participants were tested for memory performance and scanned with 3 T MRI to
assess the volume of 5 distinct hippocampal subfields using automatic
segmentation techniques. RESULTS: At baseline, CA4/dentate gyrus was the only
hippocampal subfield with a volume significantly smaller than controls (p < .01).
After one year, CA4/dentate gyrus atrophy worsened (-6.4%, p < .0001) and
significant CA1 atrophy appeared (both in the stratum-pyramidale and the stratum
radiatum-lacunosum-moleculare, -5.6%, p < .001 and -6.2%, p < .01, respectively).
CA4/dentate gyrus volume at baseline predicted CA1 volume one year after CIS (R2
= 0.44 to 0.47, p < .001, with age, T2 lesion-load, and global brain atrophy as
covariates). The volume of CA4/dentate gyrus at baseline was associated with MS
diagnosis during follow-up, independently of T2-lesion load and demographic
variables (p < .05). Whereas CA4/dentate gyrus volume was not correlated with
memory scores at baseline, CA1 atrophy was an independent correlate of episodic
verbal memory performance one year after CIS (beta = 0.87, p < .05). CONCLUSION:
The hippocampal degenerative process spread from dentate gyrus to CA1 at the
earliest stage of MS. This dynamic vulnerability is associated with MS diagnosis
after CIS and will ultimately impact hippocampal-dependent memory performance.
PMID- 29331061
TI - Lutolf R, Hughes FM, Jr., Inouye BM, Jin H, McMains JC, Pak ES, Hannan JL, Purves
JT. NLRP3/IL-1beta mediates denervation during bladder outlet obstruction in
rats. Neurourology and urodynamics 2017.
PMID- 29331057
TI - Manifestations and mechanisms of myocardial lipotoxicity in obesity.
AB - Environmental and socioeconomic changes over the past thirty years have
contributed to a dramatic rise in the worldwide prevalence of obesity. Heart
disease is amongst the most serious health risks of obesity, with increases in
both atherosclerotic coronary heart disease and heart failure among obese
individuals. In this review, we focus on primary myocardial alterations in
obesity that include hypertrophic remodelling and diastolic dysfunction. Obesity
associated perturbations in myocardial and systemic lipid metabolism are
important contributors to cardiovascular complications of obesity. Accumulation
of excess lipid in nonadipose cells of the cardiovascular system can cause cell
dysfunction and cell death, a process known as lipotoxicity. Lipotoxicity has
been modelled in mice using high-fat diet feeding, inbred lines with mutations in
leptin receptor signalling, and in genetically engineered mice with enhanced
myocardial fatty acid uptake, altered lipid droplet homoeostasis or decreased
cardiac fatty acid oxidation. These studies, along with findings in cell culture
model systems, indicate that the molecular pathophysiology of lipid overload
involves endoplasmic reticulum stress, alterations in autophagy, de novo ceramide
synthesis, oxidative stress, inflammation and changes in gene expression. We
highlight recent advances that extend our understanding of the impact of obesity
and altered lipid metabolism on cardiac function.
PMID- 29331062
TI - Benefits of increasing transpiration efficiency in wheat under elevated CO2 for
rainfed regions.
AB - Higher transpiration efficiency (TE) has been proposed as a mechanism to increase
crop yields in dry environments where water availability usually limits yield.
The application of a coupled radiation and TE simulation model shows wheat yield
advantage of a high-TE cultivar (cv. Drysdale) over its almost identical low-TE
parent line (Hartog), from about -7 to 558 kg/ha (mean 187 kg/ha) over the
rainfed cropping region in Australia (221-1,351 mm annual rainfall), under the
present-day climate. The smallest absolute yield response occurred in the more
extreme drier and wetter areas of the wheat belt. However, under elevated CO2
conditions, the response of Drysdale was much greater overall, ranging from 51 to
886 kg/ha (mean 284 kg/ha) with the greatest response in the higher rainfall
areas. Changes in simulated TE under elevated CO2 conditions are seen across
Australia with notable increased areas of higher TE under a drier climate in
Western Australia, Queensland and parts of New South Wales and Victoria. This
improved efficiency is subtly deceptive, with highest yields not necessarily
directly correlated with highest TE. Nevertheless, the advantage of Drysdale over
Hartog is clear with the benefit of the trait advantage attributed to TE ranging
from 102% to 118% (mean 109%). The potential annual cost-benefits of this
increased genetic TE trait across the wheat growing areas of Australia (5 year
average of area planted to wheat) totaled AUD 631 MIL (5-year average wheat price
of AUD/260 t) with an average of 187 kg/ha under the present climate. The benefit
to an individual farmer will depend on location but elevated CO2 raises this
nation-wide benefit to AUD 796 MIL in a 2 degrees C warmer climate, slightly
lower (AUD 715 MIL) if rainfall is also reduced by 20%.
PMID- 29331063
TI - Simultaneous pharmacokinetics and stability studies of physalins in rat plasma
and intestinal bacteria culture media using liquid chromatography with mass
spectrometry.
AB - Physalins are the major steroidal constituent of Physalis plants and display a
range of biological activities. For this study, a rapid and sensitive high
performance liquid chromatography with triple quadrupole mass spectrometry method
was developed for the simultaneous quantification of six physalins. Specifically,
it was for the quantification of physalin A, physalin B, physalin D, physalin G,
4,7-didehydroneophysalin B, and isophysalin B in rat plasma and rat intestinal
bacteria. After a solid-phase extraction, analytes and internal standards
(prednisolone) were separated on a Shield reverse-phase C18 column (measuring 3
mm * 150 mm with an internal diameter of 3.5 MUm) and determined using multiple
reactions in a monitoring mode with a positive-ion electrospray ionization
source. The mobile phase was a mixture of 0.1% formic acid in water (A) and
acetonitrile (B) and was used at a flow rate of 0.6 mL/min. The intra- and
interday precisions were within 15% with accuracies ranging from 86.2 to 114%.
The method was validated and successfully applied to pharmacokinetics and
stability studies of six physalins in rat plasma and rat intestinal bacteria,
respectively. The results showed that physalin B and isophysalin B could not be
absorbed by rats, and rat intestinal bacteria could quickly transform physalins.
PMID- 29331064
TI - Controlling the Temporal Structure of Brain Oscillations by Focused Attention
Meditation.
AB - Our focus of attention naturally fluctuates between different sources of
information even when we desire to focus on a single object. Focused attention
(FA) meditation is associated with greater control over this process, yet the
neuronal mechanisms underlying this ability are not entirely understood. Here, we
hypothesize that the capacity of attention to transiently focus and swiftly
change relates to the critical dynamics emerging when neuronal systems balance at
a point of instability between order and disorder. In FA meditation, however, the
ability to stay focused is trained, which may be associated with a more
homogeneous brain state. To test this hypothesis, we applied analytical tools
from criticality theory to EEG in meditation practitioners and meditation-naive
participants from two independent labs. We show that in practitioners-but not in
controls-FA meditation strongly suppressed long-range temporal correlations
(LRTC) of neuronal oscillations relative to eyes-closed rest with remarkable
consistency across frequency bands and scalp locations. The ability to reduce
LRTC during meditation increased after one year of additional training and was
associated with the subjective experience of fully engaging one's attentional
resources, also known as absorption. Sustained practice also affected normal
waking brain dynamics as reflected in increased LRTC during an eyes-closed rest
state, indicating that brain dynamics are altered beyond the meditative state.
Taken together, our findings suggest that the framework of critical brain
dynamics is promising for understanding neuronal mechanisms of meditative states
and, specifically, we have identified a clear electrophysiological correlate of
the FA meditation state.
PMID- 29331065
TI - Component-resolved diagnostics to direct in venom immunotherapy: Important steps
towards precision medicine.
AB - Stings of Hymenoptera can induce IgE-mediated systemic and even fatal allergic
reactions. Venom-specific immunotherapy (VIT) is the only disease-modifying and
curative treatment of venom allergy. However, choosing the correct venom for VIT
represents a necessary prerequisite for efficient protection against further
anaphylactic sting reactions after VIT. In the past, therapeutic decisions based
on the measurement of specific IgE (sIgE) levels to whole venom extracts were not
always straightforward, especially when the patient was not able to identify the
culprit insect. In the last years, the increasing knowledge about the molecular
structure and relevance of important venom allergens and their availability as
recombinant allergens, devoid of cross-reactive carbohydrate determinants,
resulted in the development of an advanced component-resolved diagnostics (CRD)
approach in venom allergy. Already to date, CRD has increased the sensitivity of
sIgE detection and enabled the discrimination between primary sensitization and
cross-reactivity, particularly in patients with sensitization to both honeybee
and vespid venom. Hence, CRD in many patients improves the selection of the
appropriate immunotherapeutic intervention. Moreover, the detailed knowledge
about sensitization profiles on a molecular level might open new options to
identify patients who are at increased risk of side-effects or not to respond to
immunotherapy. Therefore, increasing potential of CRD becomes evident, to direct
therapeutic decisions in a personalized and patient-tailored manner. Reviewed
here are the state of the art options, recent developments and future
perspectives of CRD of Hymenoptera venom allergy.
PMID- 29331068
TI - A fixed partial epithelial-mesenchymal transition (EMT) triggers carcinogenesis,
whereas asymmetrical division of hybrid EMT cells drives cancer progression.
PMID- 29331066
TI - Strong evidence for changing fish reproductive phenology under climate warming on
the Tibetan Plateau.
AB - Phenological responses to climate change have been widely observed and have
profound and lasting effects on ecosystems and biodiversity. However, compared to
terrestrial ecosystems, the long-term effects of climate change on species'
phenology are poorly understood in aquatic ecosystems. Understanding the long
term changes in fish reproductive phenology is essential for predicting
population dynamics and for informing management strategies, but is currently
hampered by the requirement for intensive field observations and larval
identification. In this study, a very low-frequency sampling of juveniles and
adults combined with otolith measurements (long axis length of the first annulus;
LAFA) of an endemic Tibetan Plateau fish (Gymnocypris selincuoensis) was used to
examine changes in reproductive phenology associated with climate changes from
the 1970s to 2000s. Assigning individual fish to their appropriate calendar year
class was assisted by dendrochronological methods (crossdating). The results
demonstrated that LAFA was significantly and positively associated with
temperature and growing season length. To separate the effects of temperature and
the growing season length on LAFA growth, measurements of larval otoliths from
different sites were conducted and revealed that daily increment additions were
the main contributor (46.3%), while temperature contributed less (12.0%). Using
constructed water-air temperature relationships and historical air temperature
records, we found that the reproductive phenology of G. selincuoensis was
strongly advanced in the spring during the 1970s and 1990s, while the increased
growing season length in the 2000s was mainly due to a delayed onset of winter.
The reproductive phenology of G. selincuoensis advanced 2.9 days per decade on
average from the 1970s to 2000s, and may have effects on recruitment success and
population dynamics of this species and other biota in the ecosystem via the food
web. The methods used in this study are applicable for studying reproductive
phenological changes across a wide range of species and ecosystems.
PMID- 29331069
TI - Cellular Membrane Trafficking Machineries Used by the Hepatitis Viruses.
AB - While the life cycles of hepatitis viruses (A, B, C, D, and E) have been modestly
characterized, recent intensive studies have provided new insights. Because these
viruses "hijack" the membrane trafficking of the host cell machinery during
replicative propagation, it is essential to determine and understand these
specific cellular pathways. Hepatitis B virus (HBV) and hepatitis C virus are
well known as leading causes of liver cirrhosis and hepatocellular carcinoma.
While substantial inroads toward treating hepatitis C virus patients have
recently been made, patients with HBV continue to require lifelong treatment,
which makes a thorough understanding of the HBV life cycle essential.
Importantly, these viruses have been observed to "hijack" the secretory and
endocytic membrane trafficking machineries of the hepatocyte. These can include
the canonical clathrin-mediated endocytic process that internalizes virus through
cell surface receptors. While these receptors are encoded by the host genome for
normal hepatocellular functions, they also exhibit virus-specific recognition.
Further, functions provided by the multivesicular body, which include endosomal
sorting complexes required for transport, are now known to envelope a variety of
different hepatitis viruses. In this review, we summarize the recent findings
regarding the cellular membrane trafficking machineries used by HBV in the
context of other hepatitis viruses. (Hepatology 2018; 00:000-000).
PMID- 29331070
TI - How does dose impact on the severity of food-induced allergic reactions, and can
this improve risk assessment for allergenic foods?: Report from an ILSI Europe
Food Allergy Task Force Expert Group and Workshop.
AB - Quantitative risk assessment (QRA) for food allergens has made considerable
progress in recent years, yet acceptability of its outcomes remains stymied
because of the limited extent to which it has been possible to incorporate
severity as a variable. Reaction severity, particularly following accidental
exposure, depends on multiple factors, related to the allergen, the host and any
treatments, which might be administered. Some of these factors are plausibly
still unknown. Quantitative risk assessment shows that limiting exposure through
control of dose reduces the rates of reactions in allergic populations, but its
impact on the relative frequency of severe reactions at different doses is
unclear. Food challenge studies suggest that the relationship between dose of
allergenic food and reaction severity is complex even under relatively controlled
conditions. Because of these complexities, epidemiological studies provide very
limited insight into this aspect of the dose-response relationship. Emerging data
from single-dose challenges suggest that graded food challenges may overestimate
the rate of severe reactions. It may be necessary to generate new data (such as
those from single-dose challenges) to reliably identify the effect of dose on
severity for use in QRA. Success will reduce uncertainty in the susceptible
population and improve consumer choice.
PMID- 29331071
TI - Hepatic PPARalpha function is controlled by polyubiquitination and proteasome
mediated degradation through the coordinated actions of PAQR3 and HUWE1.
AB - : Peroxisome proliferator-activated receptor alpha (PPARalpha) is a key
transcriptional factor that regulates hepatic lipid catabolism by stimulating
fatty acid oxidation and ketogenesis in an adaptive response to nutrient
starvation. However, how PPARalpha is regulated by posttranslational modification
is poorly understood. In this study, we identified that progestin and adipoQ
receptor 3 (PAQR3) promotes PPARalpha ubiquitination through the E3 ubiquitin
ligase HUWE1, thereby negatively modulating PPARalpha functions both in vitro and
in vivo. Adenovirus-mediated Paqr3 knockdown and liver-specific deletion of the
Paqr3 gene reduced hepatic triglyceride levels while increasing fatty acid
oxidation and ketogenesis upon fasting. PAQR3 deficiency enhanced the fasting
induced expression of PPARalpha target genes, including those involved in fatty
acid oxidation and fibroblast growth factor 21, a key molecule that mediates the
metabolism-modulating effects of PPARalpha. PAQR3 directly interacted with
PPARalpha and increased the polyubiquitination and proteasome-mediated
degradation of PPARalpha. Furthermore, the E3 ubiquitin ligase HUWE1 was
identified to mediate PPARalpha polyubiquitination. Additionally, PAQR3 enhanced
the interaction between HUWE1 and PPARalpha. CONCLUSION: Ubiquitination
modification through the coordinated action of PAQR3 with HUWE1 plays a crucial
role in regulating the activity of PPARalpha in response to starvation.
(Hepatology 2018;68:289-303).
PMID- 29331072
TI - Transcranial Ultrasonographic Image Analysis System for Decision Support in
Parkinson Disease.
AB - OBJECTIVES: Transcranial ultrasonography (US) is a relatively new neuroimaging
modality proposed for early diagnostics of Parkinson disease (PD). The main
limitation of transcranial US image-based diagnostics is a high degree of
subjectivity caused by low quality of the transcranial images. The article
presents a developed image analysis system and evaluates the potential of
automated image analysis on transcranial US. METHODS: The system consists of
algorithms for the segmentation and assessment of informative brain regions
(midbrain and substantia nigra) and a decision support subsystem, which is
equipped with 64 classification algorithms. Transcranial US images of 191
participants (118 patients with a clinical PD diagnosis and 73 healthy control
participants) were analyzed. RESULTS: The diagnostic sensitivity and specificity
achieved by the proposed system were 85% and 75%, respectively. CONCLUSIONS:
Digital transcranial US image analysis is challenging, and the application of a
such system as the sole instrument for decisions in clinical practice remains
inconclusive. However, the proposed system could be used as a supplementary tool
for automated assessment of US parameters for decision support in PD diagnostics
and to reduce observer variability.
PMID- 29331073
TI - Cerebrospinal fluid macrophage biomarkers in amyotrophic lateral sclerosis.
AB - OBJECTIVE: The neurodegenerative disease, amyotrophic lateral sclerosis (ALS), is
a heterogeneous clinical syndrome involving multiple molecular pathways. The
development of biomarkers for use in therapeutic trials is a priority. We sought
to use a high-throughput proteomic method to identify novel biomarkers in
individual cerebrospinal fluid (CSF) samples. METHODS: Liquid
chromatography/tandem mass spectrometry with label-free quantification was used
to identify CSF proteins using samples from a well-characterized longitudinal
cohort comprising patients with ALS (n = 43), the upper motor neuron variant,
primary lateral sclerosis (PLS; n = 6), and cross-sectional healthy (n = 20) and
disease controls (Parkinsons' disease, n = 20; ALS mimic disorders, n = 12).
RESULTS: Three macrophage-derived chitinases showed increased abundance in ALS:
chitotriosidase (CHIT1), chitinase-3-like protein 1 (CHI3L1), and chitinase-3
like protein 2 (CHI3L2). Elevated CHI3L1 was common to ALS and PLS, whereas CHIT1
and CHI3L2 levels differed. Chitinase levels correlated with disease progression
rate (CHIT1, r = 0.56, p < 0.001; CHI3L1, r = 0.31; p = 0.028; CHI3L2, r = 0.29,
p = 0.044). CHIT1, CHI3L1, and CHI3L2 levels correlated with phosphorylated
neurofilament heavy chain (pNFH; r = 0.62, p < 0.001; r = 0.49, p < 0.001; r =
0.41, p < 0.001). CHI3L1 levels, but not CHIT1 or CHI3L2, increased over time in
those with low initial levels (gradient = 0.005 log abundance units/month, p =
0.001). High CHIT1 was associated with shortened survival (hazard ratio [HR]
2.84; p = 0.009). Inclusion of pNFH in survival models left only an association
of pNFH and survival (HR 1.26; p = 0.019). INTERPRETATION: Neuroinflammatory
mechanisms have been consistently implicated through various experimental
paradigms. These results support a key role for macrophage activity in ALS
pathogenesis, offering novel target engagement and pharmacodynamic biomarkers for
neuroinflammation-focused ALS therapy. Ann Neurol 2018;83:258-268.
PMID- 29331074
TI - Cryopyrin-associated periodic syndrome in early childhood can be successfully
treated with interleukin-1 blockades.
AB - : Cryopyrin-associated periodic syndrome (CAPS) is caused by a mutation in the
NLRP3 gene encoding cryopyrin production. Overproduction of interleukin-1 (IL-1)
leads to symptoms that are associated with elevated inflammatory markers,
including periodic fever and a rash. We provide a clinical overview of CAPS in
children, including three Finnish case studies. CONCLUSION: When CAPS has been
diagnosed, an IL-1 blockade with biological should be introduced to lessen the
symptoms and to prevent the progression of organ damage.
PMID- 29331075
TI - An examination of the clinical outcomes of adolescents and young adults with
broad autism spectrum traits and autism spectrum disorder and anorexia nervosa: A
multi centre study.
AB - OBJECTIVES: To compare the clinical outcomes of adolescents and young adults with
anorexia nervosa (AN) comorbid with broad autism spectrum disorder (ASD) or ASD
traits. METHOD: The developmental and well-being assessment and social aptitude
scale were used to categorize adolescents and young adults with AN (N = 149) into
those with ASD traits (N = 23), and those who also fulfilled diagnostic criteria
for a possible/probable ASD (N = 6). We compared both eating disorders specific
measures and broader outcome measures at intake and 12 months follow-up. RESULTS:
Those with ASD traits had significantly more inpatient/day-patient service use (p
= .015), as well as medication use (p < .001) at baseline. Both groups had high
social difficulties and poorer global functioning (strengths and difficulties
questionnaire) at baseline, which improved over time but remained higher at 12
months in the ASD traits group (p = .002). However, the improvement in eating
disorder symptoms at 12 months was similar between groups with or without ASD
traits. Treatment completion rates between AN only and ASD traits were similar
(80.1 vs. 86.5%). DISCUSSION: Adolescents with AN and ASD traits show similar
reductions in their eating disorder symptoms. Nevertheless, their social
difficulties remain high suggesting that these are life-long difficulties rather
than starvation effects.
PMID- 29331076
TI - Submental artery island flap with simultaneous level I neck dissection.
AB - BACKGROUND: The purpose of this study was to illustrate the submental island flap
elevation technique with simultaneous level I neck dissection followed by the
inset and reconstruction of an oropharyngeal defect. METHODS: A 63-year-old
patient with a T2N1M0 human papillomavirus-positive squamous cell carcinoma of
the tonsil was treated with concurrent chemoradiotherapy (cisplatin + 66 Gy). A
local recurrence 2.5 years after treatment was treated surgically and
reconstructed with a submental island flap. RESULTS: There were no complications
and oral diet was initiated at 2 weeks and the gastrostomy tube was removed 1
month postoperatively. A video demonstration of the submental island flap
elevation is included with a focus on how levels 1A and 1B can be dissected
safely and this can be viewed online on Head & Neck's home page at
http://onlinelibrary.wiley.com/. CONCLUSION: The submental island flap can be
performed safely with a level I neck dissection for head and neck reconstruction.
PMID- 29331078
TI - Primary biliary cholangitis, DNA, and beyond: The Relative contribution of genes.
PMID- 29331077
TI - Optimized paired-sgRNA/Cas9 cloning and expression cassette triggers high
efficiency multiplex genome editing in kiwifruit.
AB - Kiwifruit is an important fruit crop; however, technologies for its functional
genomic and molecular improvement are limited. The clustered regulatory
interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas)
system has been successfully applied to genetic improvement in many crops, but
its editing capability is variable depending on the different combinations of the
synthetic guide RNA (sgRNA) and Cas9 protein expression devices. Optimizing
conditions for its use within a particular species is therefore needed to achieve
highly efficient genome editing. In this study, we developed a new cloning
strategy for generating paired-sgRNA/Cas9 vectors containing four sgRNAs
targeting the kiwifruit phytoene desaturase gene (AcPDS). Comparing to the
previous method of paired-sgRNA cloning, our strategy only requires the synthesis
of two gRNA-containing primers which largely reduces the cost. We further
compared efficiencies of paired-sgRNA/Cas9 vectors containing different sgRNA
expression devices, including both the polycistronic tRNA-sgRNA cassette (PTG)
and the traditional CRISPR expression cassette. We found the mutagenesis
frequency of the PTG/Cas9 system was 10-fold higher than that of the CRISPR/Cas9
system, coinciding with the relative expressions of sgRNAs in two different
expression cassettes. In particular, we identified large chromosomal fragment
deletions induced by the paired-sgRNAs of the PTG/Cas9 system. Finally, as
expected, we found both systems can successfully induce the albino phenotype of
kiwifruit plantlets regenerated from the G418-resistance callus lines. We
conclude that the PTG/Cas9 system is a more powerful system than the traditional
CRISPR/Cas9 system for kiwifruit genome editing, which provides valuable clues
for optimizing CRISPR/Cas9 editing system in other plants.
PMID- 29331079
TI - LMOD3-Associated Nemaline Myopathy: Prenatal Ultrasonographic, Pathologic, and
Molecular Findings.
AB - To describe the prenatal presentation, including ultrasonographic, histologic,
and molecular findings, in 2 fetuses affected with LMOD3-related nemaline
myopathy. Prenatal ultrasonographic examinations and histopathologic studies were
performed on 2 fetuses with evidence of nemaline myopathy. To establish a
molecular diagnosis, whole-exome sequencing was pursued for the affected fetuses.
Nemaline myopathy is a common form of congenital myopathy manifesting with
nonprogressive generalized muscle weakness, hypotonia, and electron-dense protein
inclusions in skeletal myofibers. Although clinically, nemaline myopathy can be
viewed as a common pathway phenotype, its molecular basis is heterogeneous, with
mutations in 11 identified genes implicated in its pathogenesis so far. Whole
exome sequencing revealed that the affected fetuses were compound heterozygous
for 2 newly reported pathogenic variants in the LMOD3 gene, which encodes
leiomodin 3. To our knowledge, this article is the first report of LMOD3-related
nemaline myopathy since the original reported cohort. We provide a detailed
description of the prenatal imaging of these affected fetuses, which we hope, in
combination with next-generation sequencing, may contribute to further diagnosis
in additional families.
PMID- 29331080
TI - Design, Synthesis and Evaluation of Oxazaborine Inhibitors of the NLRP3
Inflammasome.
AB - The NLRP3 inflammasome is an important regulator of the sterile inflammatory
response, and its activation by host-derived sterile molecules leads to the
intracellular activation of caspase-1, processing of the pro-inflammatory
cytokines interleukin-1beta (IL-1beta)/IL-18, and pyroptotic cell death.
Inappropriate activation of NLRP3 drives a chronic inflammatory response and is
implicated in several non-communicable diseases, including gout, atherosclerosis,
type II diabetes and Alzheimer's disease. In this study, we report the design,
synthesis and biological evaluation of novel boron compounds (NBCs) as NLRP3
inflammasome inhibitors. Structure-activity relationships (SAR) show that 4
fluoro substituents on the phenyl rings retain NLRP3 inhibitory activity, whereas
more steric and lipophilic substituents diminish activity. Loss of inhibitory
activity is also observed if the CCl3 group on the oxazaborine ring is replaced
by a CF3 group. These findings provide additional understanding of the NBC series
and will aid in the development of these NLRP3 inhibitors as tool compounds or
therapeutic candidates for sterile inflammatory diseases.
PMID- 29331081
TI - Quantitative [Fe]MRI determination of the dynamics of PSMA-targeted SPIONs
discriminates among prostate tumor xenografts based on their PSMA expression.
AB - BACKGROUND: There is a need for a quantitative MRI method for iron concentration
magnetic resonance imaging suitable for measuring the delivery of targeted
superparamagnetic iron oxide nanoparticles (SPIONs) to tumors. PURPOSE: To apply
our newly developed [Fe]MRI method to the quantitative imaging in both space and
time of the iron dynamics of anti-prostate specific membrane antigen (PSMA)
conjugated SPIONs within human prostate tumor xenografts in nude mice. STUDY
TYPE: Longitudinal. ANIMAL MODEL: 45 Harlan Sprague Dawley athymic nude mice
bearing xenografts from PSMA-positive LNCaP, C4-2 and PSMA-negative DU145 tumors
from human prostate tumor cell lines. FIELD STRENGTH/SEQUENCE: 1.0 Tesla/ T1 and
T2 weighted spin echo. ASSESSMENT: Image intensity and contrast measurements.
STATISTICAL TESTS: Student's t-test. RESULTS: The SPION diffusion coefficient
within tumors was D = 44.8 +/- 2.4 * 10-6 mm2 /s. The iron taken up by PSMA
positive LNCaP and C4-2 tumors was proportional to the tail-vein injected dose
from 60 nmol to 1.6 MUmol; injection of 1 MUmol of iron in anti-PSMA conjugated
SPIONs resulted in a tumor [Fe] of 76 MUM. Even at the highest iron dose of 1.6
MUmol, the PSMA-negative DU145 tumors took up no significant iron from the anti
PSMA conjugated SPIONs. A similar lack of nonspecific uptake was observed when
the antibodies against PSMA were omitted from the injected SPION preparation. The
fraction of the initial iron dose that was taken up by PSMA-positive tumors was
2.32 +/- 0.75% (n = 10); uptake by the PSMA-negative DU145 tumors and for SPIONs
without anti-PSMA antibodies was 0.16 +/- 0.34% (n = 7) giving a ratio of [Fe] in
PSMA + versus PSMA- tumors greater than 15:1 (P = 0.01). DATA CONCLUSION:
Quantitative [Fe]MRI of anti-PSMA conjugated SPIONs discriminated between PSMA
positive LNCaP and C4-2 and PSMA-negative DU145 human prostate tumor xenografts
in vivo. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging
2017. J. MAGN. RESON. IMAGING 2018;48:469-481.
PMID- 29331083
TI - Variation in reproductive outcomes of women with histories of bulimia nervosa,
anorexia nervosa, or eating disorder not otherwise specified relative to the
general population and closest-aged sisters.
AB - OBJECTIVE: This study seeks to examine the long-term reproductive consequences of
eating disorders (ED), to assess variation in reproductive outcomes by ED type,
and to examine reproductive differences between women with previous ED diagnosis
and their discordant sisters. METHOD: Using a sample of women with previous ED
diagnosis generated by the Utah Population Database, this study compares the
fecundity (parity) and age at first birth of women by ED subtype (bulimia nervosa
[BN], anorexia nervosa [AN], and ED not otherwise specified [EDNOS]) (n = 1,579).
We also employed general population match case-control, and discordant sibling
pair analyses, to estimate the magnitude of association between EDs and
reproductive outcomes. RESULTS: Women previously diagnosed with AN or EDNOS
experienced delayed first birth (HRR = 0.33, HRR = 0.34, respectively) and lower
parity (IRR = 0.19, IRR = 0.22, respectively) relative to BN (p < .05), the
general population (p < .05), and closest-aged sisters (p < .05). Women
previously diagnosed with BN experienced more moderate reductions and delays to
their reproduction, and had similar reproductive outcomes as their discordant
sisters. DISCUSSION: Clinicians should consider ED type and family fertility
histories when addressing the long-term reproductive health needs of women with
prior AN, BN, or EDNOS diagnosis. Women previously diagnosed with AN or EDNOS
likely experience the greatest reductions and delays in reproduction across their
lifespan. Reproductive health screenings may be especially critical for the
wellbeing of women with a history of AN or EDNOS.
PMID- 29331082
TI - Mechanistic target of rapamycin complex 1 and 2 in human temporal lobe epilepsy.
AB - OBJECTIVE: Temporal lobe epilepsy (TLE) is a chronic epilepsy syndrome defined by
seizures and progressive neurological disabilities, including cognitive
impairments, anxiety, and depression. Here, human TLE specimens were investigated
focusing on the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) and
complex 2 (mTORC2) activities in the brain, given that both pathways may
represent unique targets for treatment. METHODS: Surgically resected hippocampal
and temporal lobe samples from therapy-resistant TLE patients were analyzed by
western blotting to quantify the expression of established mTORC1 and mTORC2
activity markers and upstream or downstream signaling pathways involving the two
complexes. Histological and immunohistochemical techniques were used to assess
hippocampal and neocortical structural abnormalities and cell-specific expression
of individual biomarkers. Samples from patients with focal cortical dysplasia
(FCD) type II served as positive controls. RESULTS: We found significantly
increased expression of phospho-mTOR (Ser2448), phospho-S6 (Ser235/236), phospho
S6 (Ser240/244), and phospho-Akt (Ser473) in TLE samples compared to controls,
consistent with activation of both mTORC1 and mTORC2. Our work identified the
phosphoinositide 3-kinase and Ras/extracellular signal-regulated kinase signaling
pathways as potential mTORC1 and mTORC2 upstream activators. In addition, we
found that overactive mTORC2 signaling was accompanied by induction of two
protein kinase B-dependent prosurvival pathways, as evidenced by increased
inhibitory phosphorylation of forkhead box class O3a (Ser253) and glycogen
synthase kinase 3 beta (Ser9). INTERPRETATION: Our data demonstrate that mTOR
signaling is significantly dysregulated in human TLE, offering new targets for
pharmacological interventions. Specifically, clinically available drugs that
suppress mTORC1 without compromising mTOR2 signaling, such as rapamycin and its
analogs, may represent a new group of antiepileptogenic agents in TLE patients.
Ann Neurol 2018;83:311-327.
PMID- 29331084
TI - British Association of Urological Surgeons (BAUS) consensus document for the
management of male genital emergencies - penile amputation.
AB - Male genital emergencies relating to the penis and scrotum are rare and require
prompt investigation and surgical intervention. Clinicians are often unfamiliar
with the management of these conditions and may not work in a specialist centre
with on-site expertise in genitourethral surgery. A series of consensus
statements have been developed by an expert consensus committee comprising
members of the British Association of Urological Surgeons (BAUS) Section of
Andrology and Genitourethral Surgery together with experts from urology units
throughout the UK. Penile amputation is a rare genital emergency, which requires
prompt intervention and microsurgical reconstruction. The consensus statements
will outline the management of these cases for non-specialist units, as well as
recommendations for reconstruction for specialists.
PMID- 29331085
TI - Verification of DNA motifs in Arabidopsis using CRISPR/Cas9-mediated mutagenesis.
AB - Transcription factors (TFs) and chromatin-modifying factors (CMFs) access
chromatin by recognizing specific DNA motifs in their target genes. Chromatin
immunoprecipitation followed by next-generation sequencing (ChIP-seq) has been
widely used to discover the potential DNA-binding motifs for both TFs and CMFs.
Yet, an in vivo method for verifying DNA motifs captured by ChIP-seq is lacking
in plants. Here, we describe the use of clustered regularly interspaced short
palindromic repeat (CRISPR)/CRISPR-associated 9 (Cas9) to verify DNA motifs in
their native genomic context in Arabidopsis. Using a single-guide RNA (sgRNA)
targeting the DNA motif bound by REF6, a DNA sequence-specific H3K27 demethylase
in plants, we generated stable transgenic plants where the motif was disrupted in
a REF6 target gene. We also deleted a cluster of multiple motifs from another
REF6 target gene using a pair of sgRNAs, targeting upstream and downstream
regions of the cluster, respectively. We demonstrated that endogenous genes with
motifs disrupted and/or deleted become inaccessible to REF6. This strategy should
be widely applicable for in vivo verification of DNA motifs identified by ChIP
seq in plants.
PMID- 29331086
TI - Current management of small bowel obstruction in the UK: results from the
National Audit of Small Bowel Obstruction clinical practice survey.
AB - AIM: Small bowel obstruction (SBO) is associated with high rates of morbidity and
mortality. The National Audit of Small Bowel Obstruction (NASBO) is a
collaboration between trainees and specialty associations to improve the care of
patients with SBO through national clinical audit. The aim of this study was to
define current consultant practice preferences in the management of SBO in the
UK. METHOD: A survey was designed to assess practice preferences of consultant
surgeons. The anonymous survey captured demographics, indications for surgery or
conservative management, use of investigations including water-soluble contrast
agents (WSCA), use of laparoscopy and nutritional support strategies. The
questionnaire underwent two pilot rounds prior to dissemination via the NASBO
network. RESULTS: A total of 384 responses were received from 131 NASBO
participating units (overall response rate 29.2%). Abdominal CT and serum urea
and electrolytes were considered essential initial investigations by more than
80% of consultants. Consensus was demonstrated on indications for early surgery
and conservative management. Three hundred and thirty-eight (88%) respondents
would consider use of WSCA; of these, 328 (97.1%) would use it in adhesive SBO.
Two hundred (52.1%) consultants considered a laparoscopic approach when operating
for SBO. Oral nutritional supplements were favoured in operatively managed
patients by 259 (67.4%) respondents compared with conservatively managed patients
(186 respondents, 48.4%). CONCLUSION: This survey demonstrates consensus on
imaging requirements and indications for early surgery in the management of SBO.
Significant variation exists around awareness of the need for nutritional support
in patients with SBO, and on strategies to achieve this support.
PMID- 29331087
TI - Outdoor pollen is a trigger of child and adolescent asthma emergency department
presentations: A systematic review and meta-analysis.
AB - BACKGROUND: In the context of increased asthma exacerbations associated with
climatic changes such as thunderstorm asthma, interest in establishing the link
between pollen exposure and asthma hospital admissions has intensified. Here, we
systematically reviewed and performed a meta-analysis of studies on pollen and
emergency department (ED) attendance. METHODS: A search for studies with
appropriate search strategy in MEDLINE, EMBASE, Web of Science and CINAHL was
conducted. Each study was assessed for quality and risk of bias. The available
evidence was summarized both qualitatively and meta-analysed using random-effects
models when moderate heterogeneity was observed. RESULTS: Fourteen studies were
included. The pollen taxa investigated differed between studies, allowing meta
analysis only of the effect of grass pollen. A statistically significant increase
in the percentage change in the mean number of asthma ED presentations (MPC)
(pooled results from 3 studies) was observed for an increase in 10 grass pollen
grains per cubic metre of exposure 1.88% (95% CI = 0.94%, 2.82%). Time series
studies showed positive correlations between pollen concentrations and ED
presentations. Age-stratified studies found strongest associations in children
aged 5-17 years old. CONCLUSION: Exposure to ambient grass pollen is an important
trigger for childhood asthma exacerbations requiring ED attendance. As pollen
exposure is increasingly a problem especially in relation to thunderstorm asthma,
studies with uniform measures of pollen and similar analytical methods are
necessary to fully understand its impact on human health.
PMID- 29331088
TI - Significance of circulatory DPP4 activity in metabolic diseases.
AB - Dipeptidyl peptidase 4 (DPP4), also known as CD26 is a type II transmembrane
protein that is released from the cell membrane in a nonclassical secretory
mechanism. This exopeptidase selectively degrades varieties of substrates
including incretin hormones, growth factors, and cytokines. A significant
detectable amount of DPP4 activity can be measured in plasma as well as in
different tissues such as intestinal epithelium, vascular endothelium,
lymphocytes, monocytes, kidney, liver, adipose, lung, thymus, spleen, prostate,
etc. Enzymatically active circulatory DPP4 is shed from the plasma membrane via
proteolytic cleavage, a process responsible for the enhanced plasma DPP4 levels
and activity. Elevated circulatory DPP4 activity as well as levels has been found
in wide spectrum of metabolic diseases including diabetes, obesity,
cardiovascular diseases, and nonalcoholic fatty liver diseases. Moreover, recent
preclinical studies have further expanded the repertoire for the usage of DPP4
inhibitors in the treatment of other metabolic diseases and in their consequent
complications. In the present review we highlight the reason behind the elevated
circulatory DPP4 levels in metabolic diseases with a focus on the tissue of
origin. We also underscore the discrepancy of protein levels with enzyme activity
of circulatory DPP4 in metabolic diseases. (c) 2018 IUBMB Life, 70(2):112-119,
2018.
PMID- 29331090
TI - Enhanced chondrogenesis of mesenchymal stem cells over silk fibroin/chitosan
chondroitin sulfate three dimensional scaffold in dynamic culture condition.
AB - Chondroitin sulfate (Ch) is one of the main structural components of cartilage
tissue, therefore, its presence in tissue engineered scaffold is expected to
enhance cartilage regeneration. Previously, silk fibroin/chitosan (SF/CS) blend
was proven to be a potential biomaterial for tissue development. In this study,
the effect of Ch on physicochemical and biological properties of SF/CS blend was
investigated and scaffolds with 0.8 wt% Ch was found to be favorable. The
scaffolds possess pore size of 37-212 um, contact angle 46.2-50.3 degrees ,
showed controlled swelling and biodegradation. The biocompatibility of scaffold
was confirmed by subcutaneous implantation in mouse. Human mesenchymal stem cells
(hMSCs) seeded scaffolds cultured under spinner flask bioreactor promoted cell
attachment, proliferation, distribution, and metabolic activity in vitro. The
histology and immunofluorescence studies revealed that combined effect of Ch and
dynamic condition resulted in higher glycosaminoglycan secretion and native
cartilage type matrix synthesis in comparison to SF/CS scaffolds used as control.
Higher expression of collagen-II, Sox9, aggrecan and decrease in collagen-I
expression represented by quantitative polymerase chain reaction study confirmed
the progression of chondrogenic differentiation. This study successfully
demonstrates the potentiality of SF/CS-Ch scaffold for hMSCs recruitment and
redirecting cartilage tissue regeneration with enhanced chondrogenesis. (c) 2018
Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2576
2587, 2018.
PMID- 29331089
TI - Modification of chrysanthemum odour and taste with chrysanthemol synthase induces
strong dual resistance against cotton aphids.
AB - Aphids are pests of chrysanthemum that employ plant volatiles to select host
plants and ingest cell contents to probe host quality before engaging in
prolonged feeding and reproduction. Changes in volatile and nonvolatile
metabolite profiles can disrupt aphid-plant interactions and provide new methods
of pest control. Chrysanthemol synthase (CHS) from Tanacetum cinerariifolium
represents the first committed step in the biosynthesis of pyrethrin ester
insecticides, but no biological role for the chrysanthemol product alone has yet
been documented. In this study, the TcCHS gene was over-expressed in
Chrysanthemum morifolium and resulted in both the emission of volatile
chrysanthemol (ca. 47 pmol/h/gFW) and accumulation of a chrysanthemol glycoside
derivative, identified by NMR as chrysanthemyl-6-O-malonyl-beta-D-glucopyranoside
(ca. 1.1 mM), with no detrimental phenotypic effects. Dual-choice assays
separately assaying these compounds in pure form and as part of the headspace and
extract demonstrated independent bioactivity of both components against the
cotton aphid (Aphis gossypii). Performance assays showed that the TcCHS plants
significantly reduced aphid reproduction, consistent with disturbance of aphid
probing activities on these plants as revealed by electropenetrogram (EPG)
studies. In open-field trials, aphid population development was very strongly
impaired demonstrating the robustness and high impact of the trait. The results
suggest that expression of the TcCHS gene induces a dual defence system, with
both repellence by chrysanthemol odour and deterrence by its nonvolatile
glycoside, introducing a promising new option for engineering aphid control into
plants.
PMID- 29331091
TI - Terminal spreading depolarization and electrical silence in death of human
cerebral cortex.
AB - OBJECTIVE: Restoring the circulation is the primary goal in emergency treatment
of cerebral ischemia. However, better understanding of how the brain responds to
energy depletion could help predict the time available for resuscitation until
irreversible damage and advance development of interventions that prolong this
span. Experimentally, injury to central neurons begins only with anoxic
depolarization. This potentially reversible, spreading wave typically starts 2 to
5 minutes after the onset of severe ischemia, marking the onset of a toxic
intraneuronal change that eventually results in irreversible injury. METHODS: To
investigate this in the human brain, we performed recordings with either subdural
electrode strips (n = 4) or intraparenchymal electrode arrays (n = 5) in patients
with devastating brain injury that resulted in activation of a Do Not Resuscitate
Comfort Care order followed by terminal extubation. RESULTS: Withdrawal of life
sustaining therapies produced a decline in brain tissue partial pressure of
oxygen (pti O2 ) and circulatory arrest. Silencing of spontaneous electrical
activity developed simultaneously across regional electrode arrays in 8 patients.
This silencing, termed "nonspreading depression," developed during the steep
falling phase of pti O2 (intraparenchymal sensor, n = 6) at 11 (interquartile
range [IQR] = 7-14) mmHg. Terminal spreading depolarizations started to propagate
between electrodes 3.9 (IQR = 2.6-6.3) minutes after onset of the final drop in
perfusion and 13 to 266 seconds after nonspreading depression. In 1 patient,
terminal spreading depolarization induced the initial electrocerebral silence in
a spreading depression pattern; circulatory arrest developed thereafter.
INTERPRETATION: These results provide fundamental insight into the neurobiology
of dying and have important implications for survivable cerebral ischemic
insults. Ann Neurol 2018;83:295-310.
PMID- 29331094
TI - Solvent Impedes CO2 Cycloaddition on Metal-Organic Frameworks.
AB - The catalytic performance of metal-organic frameworks (MOFs) for the synthesis of
cyclic carbonate from carbon dioxide and epoxides has been explored under solvent
and solvent-free conditions, respectively. It was found that MOF catalysts have
significantly improved catalytic activities in solvent-free CO2 cycloaddition
reactions than those in solvent. The mechanism was discussed with regard to the
competition of solvent with substrate to adhere MOF catalysts during the reaction
process.
PMID- 29331092
TI - Deep gray matter volume loss drives disability worsening in multiple sclerosis.
AB - OBJECTIVE: Gray matter (GM) atrophy occurs in all multiple sclerosis (MS)
phenotypes. We investigated whether there is a spatiotemporal pattern of GM
atrophy that is associated with faster disability accumulation in MS. METHODS: We
analyzed 3,604 brain high-resolution T1-weighted magnetic resonance imaging scans
from 1,417 participants: 1,214 MS patients (253 clinically isolated syndrome
[CIS], 708 relapsing-remitting [RRMS], 128 secondary-progressive [SPMS], and 125
primary-progressive [PPMS]), over an average follow-up of 2.41 years (standard
deviation [SD] = 1.97), and 203 healthy controls (HCs; average follow-up = 1.83
year; SD = 1.77), attending seven European centers. Disability was assessed with
the Expanded Disability Status Scale (EDSS). We obtained volumes of the deep GM
(DGM), temporal, frontal, parietal, occipital and cerebellar GM, brainstem, and
cerebral white matter. Hierarchical mixed models assessed annual percentage rate
of regional tissue loss and identified regional volumes associated with time-to
EDSS progression. RESULTS: SPMS showed the lowest baseline volumes of cortical GM
and DGM. Of all baseline regional volumes, only that of the DGM predicted time-to
EDSS progression (hazard ratio = 0.73; 95% confidence interval, 0.65, 0.82; p <
0.001): for every standard deviation decrease in baseline DGM volume, the risk of
presenting a shorter time to EDSS worsening during follow-up increased by 27%. Of
all longitudinal measures, DGM showed the fastest annual rate of atrophy, which
was faster in SPMS (-1.45%), PPMS (-1.66%), and RRMS (-1.34%) than CIS (-0.88%)
and HCs (-0.94%; p < 0.01). The rate of temporal GM atrophy in SPMS (-1.21%) was
significantly faster than RRMS (-0.76%), CIS (-0.75%), and HCs (-0.51%).
Similarly, the rate of parietal GM atrophy in SPMS (-1.24-%) was faster than CIS
(-0.63%) and HCs (-0.23%; all p values <0.05). Only the atrophy rate in DGM in
patients was significantly associated with disability accumulation (beta = 0.04;
p < 0.001). INTERPRETATION: This large, multicenter and longitudinal study shows
that DGM volume loss drives disability accumulation in MS, and that temporal
cortical GM shows accelerated atrophy in SPMS than RRMS. The difference in
regional GM atrophy development between phenotypes needs to be taken into account
when evaluating treatment effect of therapeutic interventions. Ann Neurol
2018;83:210-222.
PMID- 29331093
TI - Sensitivity to audio-visual synchrony and its relation to language abilities in
children with and without ASD.
AB - : Autism Spectrum Disorder (ASD) is often accompanied by deficits in speech and
language processing. Speech processing relies heavily on the integration of
auditory and visual information, and it has been suggested that the ability to
detect correspondence between auditory and visual signals helps to lay the
foundation for successful language development. The goal of the present study was
to examine whether young children with ASD show reduced sensitivity to temporal
asynchronies in a speech processing task when compared to typically developing
controls, and to examine how this sensitivity might relate to language
proficiency. Using automated eye tracking methods, we found that children with
ASD failed to demonstrate sensitivity to asynchronies of 0.3s, 0.6s, or 1.0s
between a video of a woman speaking and the corresponding audio track. In
contrast, typically developing children who were language-matched to the ASD
group, were sensitive to both 0.6s and 1.0s asynchronies. We also demonstrated
that individual differences in sensitivity to audiovisual asynchronies and
individual differences in orientation to relevant facial features were both
correlated with scores on a standardized measure of language abilities. Results
are discussed in the context of attention to visual language and audio-visual
processing as potential precursors to language impairment in ASD. Autism Res
2018, 11: 645-653. (c) 2018 International Society for Autism Research, Wiley
Periodicals, Inc. LAY SUMMARY: Speech processing relies heavily on the
integration of auditory and visual information, and it has been suggested that
the ability to detect correspondence between auditory and visual signals helps to
lay the foundation for successful language development. The goal of the present
study was to explore whether children with ASD process audio-visual synchrony in
ways comparable to their typically developing peers, and the relationship between
preference for synchrony and language ability. Results showed that there are
differences in attention to audiovisual synchrony between typically developing
children and children with ASD. Preference for synchrony was related to the
language abilities of children across groups.
PMID- 29331095
TI - Household food insecurity and its association with morbidity report among school
adolescent in Jimma zone, Ethiopia.
AB - Background Household food insecurity has a substantial contribution to poor
health outcomes among young children and adolescents. Food insecurity also
affects optimal cognitive development and physiological function of these
vulnerable groups. There is a gap of documented data regarding the association of
food insecurity and morbidity among school adolescents in Ethiopia. Objective The
aim of this study is to assess the interrelationship of household food insecurity
and morbidity report among school adolescent in Jimma zone, Ethiopia. Methods A
community based cross-sectional study was done from October to November, 2013.
Data were gathered using structured questionnaires through interview of students
and their caregivers. A total of 1000 students were selected by using simple
random sampling methods using their rosters as a frame. Data were also checked
for missing values and outliers, and analyzed using SPSS version 16.0. Regression
analyses were used to see the strength of association between independent and
dependent variables using odds ratios and 95% of confidence intervals. Results
Adolescents from food insecure households had more reported illness (39.3%) than
adolescents from food secure households (24.7%) (p < 0.001). Adolescents from
food insecure households were two times more exposed to morbidity [AOR =
2.04(1.32, 3.14)] than adolescents from food secure households. This study also
showed that males had 48% less reported illness [AOR = 0.52(0.01, 0.23)] than
females. Adolescents who had attended health education had less reported illness
[AOR = 0.57(0.38, 0.86)] than those who did not ever attend. This study also
showed that having a farmer [AOR = 0.46(0.28, 0.74)] and government employee [AOR
= 0.33 (0.17, 0.64)] father were inversely associated with adolescent morbidity.
Conclusion The findings of this study showed that household food insecurity,
female gender and lack of attending health education had a significant
contribution to adolescent morbidity. Therefore, there is a need to improve
household income earning capacity and strengthen school based health and
nutrition education to prevent adolescent morbidity. The findings of this study
can also be used to lead the development of programs aimed at preventing
adolescent morbidity by notifying policymakers and other stakeholders about the
association of morbidity with household food insecurity.
PMID- 29331096
TI - Promoting physical activity and improving dietary quality of Singaporean
adolescents: effectiveness of a school-based fitness and wellness program.
AB - Limited data are available on the effectiveness of the school-based structured
fitness and wellness program to influence dietary quality and physical activity
levels in Singaporean adolescents. The study examined if a 20-h (over 10 weeks)
school-based structured fitness and wellness module affects the diet quality
indices, energy intakes, physical activity levels and the associated energy
expenditures in a group of healthy, male adolescents with low diet quality and
physical activity levels. Participant demography, anthropometry, dietary intake
and daily physical activity were obtained at the beginning, mid-point and end of
the 10-week program. Physical activity levels were assessed accelerometrically
over a 1-weekday period. Dietary intake were taken using a structured 7-day food
diary, and diet quality assessed using the Diet Quality Index-International (DQI
I). The 31 enrolled participants (age 19.8 +/- 0.6 years) with body mass index
(BMI) (19.8 +/- 0.6 kg/m2) followed diets of low diet quality scores (48.3 +/-
9.6 out of 100) and engaged in 3.87 +/- 2.00 h of physical activity daily before
the start of the intervention. Their dietary quality and physical activity levels
did not change significantly throughout the intervention period. They scored
poorly in the moderation and overall balance components of the diet quality
assessment. The physical activity duration correlated inversely to the diet
quality scores. Our results suggest that the prescribed school-based fitness and
wellness module was ineffective in influencing the diet quality and physical
activity levels of Singaporean male adolescents with low diet quality and
physical activity levels.
PMID- 29331097
TI - Vigorous physical activity, perceived stress, sleep and mental health among
university students from 23 low- and middle-income countries.
AB - Background Vigorous physical activity (VPA) may be beneficial for mental health.
The aim of the study was to investigate cross-sectional associations between VPA,
perceived stress, sleep quality and quantity and mental health among university
students. Methods In a cross-sectional study, using anonymous questionnaires,
data was collected from 15122 (42.1% male and 57.9% female) university students
[mean age 20.6, standard deviation (SD) = 2.0] from 23 countries in the Americas,
Africa and Asia. They were assessed using the International Physical Activity
Questionnaire (short version), and measures of sociodemographic, health status,
health behaviour and anthropometrics. Results Students who met VPA
recommendations were less likely to report perceived stress, more likely to
report subjective good health and depression than students without VPA. There was
no association between VPA and sleep quality and quantity and PTSD symptoms.
Conclusion This study only found partial benefits of VPA in relation to well
being of university students.
PMID- 29331098
TI - Blunted cortisol reactivity and risky driving in young offenders - a pilot study.
AB - Adolescent risky driving is a significant burden on public health. Young
offenders (i.e. under custody and supervision of the criminal justice system) may
be particularly vulnerable, but research is scant. Previous work indicated that
blunted cortisol reactivity to stress is a marker of risk-taking predisposition,
including risky driving. In this study, we hypothesized that young offenders
display higher levels of risky driving than a non-offender comparison group, and
that cortisol reactivity contributes to the variance in risky driving independent
of other associated characteristics (i.e. impulsivity, risk taking, alcohol and
drug use). We found that young offenders (n = 20) showed riskier driving in
simulation than comparison group (n = 9), and blunted cortisol reactivity was
significantly associated with risky driving. The results suggest young offenders
are prone to risky driving, and that individual differences in the cortisol
stress response may be an explanatory factor.
PMID- 29331099
TI - Adaptation and validation of the disruptive behaviour disorders teacher rating
scale as a screening tool for early detection of disruptive behaviour disorders
in schools in a lower-middle income setting.
AB - Background Despite the need to curb the menace resulting from the negative
trajectory of disruptive behaviour disorders (DBD) in societies of the world
today, there is yet a dearth of locally standardised tools for the early
detection of these disorders in Nigeria. This study was aimed at standardising
the DBD teacher rating scale (DBD-TRS) to be culturally specific using teachers'
ratings of their students. Objectives To establish norm scores for the three
categories of DBD on the DBD-TRS, to evaluate the reliability, validity,
predictive power, sensitivity and specificity of DBD-TRS items for identifying
DBD symptoms amongst children/adolescents between the ages of 4 and 16 years.
Methods A cross-sectional survey of the five divisions of Lagos was conducted
using multi-stage sampling technique. A randomly selected sample of teachers from
a selection of regular schools across the five divisions of Lagos retrospectively
rated systematically selected samples of their students in absentia; by referring
to the names in their class registers for the recently concluded school session.
The DBD-TRS and the previously validated strengths and difficulties questionnaire
(SDQ) were used for the ratings. Results Ratings were completed for 1508
children/adolescents by 197 teachers from 30 regular schools. The norm scores for
the three categories of DBD were determined by gender, age, and grade/class.
Satisfactory psychometric properties were established for the DBD rating scale.
All DBD items had high negative predictive power and positive predictive power,
high specificity, and low false positive rates. However, ADHD items had lower PPP
(0.23-0.55). Conclusion The DBD rating scale demonstrated sufficient technical
merits to be used as a preliminary tool for identifying children that may require
further clinical evaluation by mental health experts for behavioural disorders.
PMID- 29331100
TI - Prevalence, associated factors, and control level of asthma symptoms among
adolescents in Northern Jordan.
AB - Objective To investigate the prevalence, associated factors, and control level of
asthma in Jordanian high school students. Methods A descriptive, comparative,
cross sectional design was used and a cluster sample of 2691 students (mean age =
14.5 years, 51.0% girls), drawn from eight randomly selected public high schools
in Northern Jordan, participated in the study. Each student had the International
Study of Asthma and Allergies in Childhood (ISAAC) questionnaire completed in the
classroom between February and May, 2015. Results The prevalence of recent
wheezing in the last 12 months was 11.7% whereas the prevalence of diagnosed
asthma was 6.2%. About 49% of students experienced cough all the time, and 33.5%
experienced waking up at night due to wheezing some of the time. About 30.9% of
students reported moderate to big exercise-induced asthma. The mean total Asthma
Control Test (ACT) score was 5.85 (SD = 3.56) with all of students reporting
uncontrolled asthma during the last month. Higher rates of asthma symptoms were
reported by females, 10th graders, and students with negative family history.
Importantly, students with diagnosed asthma or recent wheezing reported higher
rates of ever smoking tobacco vs. non-asthmatics (p < 0.000); dual (18.6% vs.
9.8%), cigarettes only (11.2% vs. 7.3%), and waterpipe only (18.0% vs. 14.7%).
Conclusion Overall, students with asthma or wheezing had increased rates of
tobacco smoking. Policies need to be set and enforced to provide a better
environment for these youth, especially making all schools smoke-free zones. A
multifaceted, comprehensive awareness and management program is required in
schools to control and manage asthma symptoms.
PMID- 29331101
TI - Theory analysis for Pender's health promotion model (HPM) by Barnum's criteria: a
critical perspective.
AB - Background Analysis of nursing theoretical works and its role in knowledge
development is presented as an essential process of critical reflection. Health
promotion model (HPM) focuses on helping people achieve higher levels of well
being and identifies background factors that influence health behaviors.
Objectives This paper aims to evaluate, and critique HPM by Barnum's criteria.
Methods The present study reviewed books and articles derived from Proquest,
PubMed, Blackwell Databases. The method of evaluation for this model is based on
Barnum's criteria for analysis, application and evaluation of nursing theories.
The criteria selected by Barnum embrace both internal and external criticism.
Internal criticism deals with how theory components fit with each other (internal
construction of theory) and external criticism deals with the way in which theory
relates to the extended world (which considers theory in its relationships to
human beings, nursing, and health). Results The electronic database search
yielded over 27,717 titles and abstracts. Following removal of duplicates, 18,963
titles and abstracts were screened using the inclusion criteria and 1278
manuscripts were retrieved. Of these, 80 were specific to HPM and 23 to analysis
of any theory in nursing relating to the aim of this article. After final
selection using the inclusion criteria for this review, 28 manuscripts were
identified as examining the factors contributing to theory analysis. Evaluation
of health promotion theory showed that the philosophical claims and their content
are consistent and clear. HPM has a logical structure and was applied to diverse
age groups from differing cultures with varying health concerns. Conclusion In
conclusion, among the strategies for theory critique, the Barnum approach is
structured and accurate, considers theory in its relationship to human beings,
community psychiatric nursing, and health. While according to Pender, nursing
assessment, diagnosis and interventions are utilized to operationalize the HPM
through practical application and research.
PMID- 29331102
TI - Opposite-sex relationship questionnaire for female adolescents: development and
psychometric evaluation.
AB - Aim The goal of the present study is to adopt state-of-the-art techniques and
standards to develop and evaluate a measure, called the opposite-sex relationship
questionnaire for female adolescents (OSRQFA), to assess the reasons why
adolescent girls would or would not develop, a relationship with an adolescent
boy. Methods A mixed-method, sequential, exploratory design was adopted. In the
qualitative phase, an in-depth interview approach was used to identify the
properties and dimensions to be included in the OSRQFA. In the quantitative
phase, the psychometric properties of the OSRQFA were evaluated according to
face, content and construct validity. Reliability and stability were assessed
with Cronbach's alpha and test-retest analysis, respectively. Results A
preliminary questionnaire including 86 items which emerged from the qualitative
phase of the study was designed. Based on the impact scores for face validity and
the cutoff points for the content validity ratio (CVR) and content validity index
(CVI), the preliminary questionnaire was reduced to 57 items. The Kaiser criteria
(eigenvalues >1) and scree plot tests demonstrated that 21 items forming six
factors, which were labeled 'innate predilection', 'abstinence', 'peer pressure',
'fear of the relationship consequences', 'family atmosphere' and 'risk taking',
that accounted for an estimated 66.19% of variance provided an optimal fit with
the data. These scales had acceptable levels of internal consistency (alpha =
0.822) and stability (r = 0.871, p < 0.001). Conclusion The OSRQFA with 21 items
and 6 factors demonstrated suitable validity and reliability in a sample of
Iranian female adolescents. The OSRQFA's has good psychometric properties, and
can be used by other researchers in future studies.
PMID- 29331103
TI - Comparison of coronary risk factors and angiographic findings in younger and
older patients with significant coronary artery disease.
AB - BACKGROUND: Coronary artery disease (CAD) is uncommon among young adults and may
have certain characteristics that are different from those in older patients. The
aim of the current study was to determine the risk factors of CAD, important
laboratory data and angiographic findings in young patients with CAD and to
compare them with the old patients. METHODS: Patients with typical chest pain
whose CAD was confirmed by coronary angiography were included in the study. These
patients were divided into 2 groups: >= 45 and < 45 years old; the risk factors
of CAD and angiographic findings were determined in each group and further
compared. RESULTS: Finally, 231 patients with CAD were included in the study.
Thirty-five (30.4%) of patients younger than 45 years and 58 (50.0%) aged >= 45
had diabetes mellitus (P = 0.002). Statistically remarkable differences were
observed between the two groups regarding hypertension (P < 0.001), myocardial
infarction (P < 0.001), Gensini score Median (P < 0.001), ejection fraction in
echocardiography (P < 0.001) and fasting blood sugar in laboratory data (P =
0.006). The older group, compared with the younger one, had higher left anterior
descending (LAD) artery (P < 0.001), right coronary artery (RCA) (P < 0.001), 3
vessel disease (P < 0.001) and 2-vessel disease (P = 0.044); on the other hand, 1
vessel disease was higher in patients aged < 45(P < 0.001). CONCLUSION: The risk
profile and angiographic findings are different in young patients with CAD
compared to older patients. Young patients with CAD tend to be male with a
positive familial history, but with less diabetes or hypertension. The older
patients had higher 3 vessel disease, 2-vessel disease and left anterior
descending (LAD) artery and right coronary artery (RCA) involvements. In
contrast, 1-vessel disease was higher in young patients aged <45.
PMID- 29331105
TI - Dietary Factors Modulate Colonic Tumorigenesis Through the Interaction of Gut
Microbiota and Host Chloride Channels.
AB - SCOPE: In recent decades, the association among diet, gut microbiota, and the
risk of colorectal cancer (CRC) has been established. Gut microbiota and
associated metabolites, such as bile acids and butyrate, are now known to play a
key role in CRC development. The aim of this study is to identify that the
progression to CRC is influenced by cholic acid, sodium butyrate, a high-fat
diet, or different dose of dihydromyricetin (DMY) interacted with gut microbiota.
METHODS AND RESULTS: An AOM/DSS (azoxymethan/dextran sodium sulfate) model is
established to study the gut microbiota compsition before and after tumor
formation during colitis-induced tumorigenesis. All above dietary factors
profoundly influence the composition of gut microbiota and host colonic
tumorigenesis. In addition, mice with DMY-modified initial microbiota display
different degrees of chemically induced tumorigenesis. Mechanism analysis reveals
that gut microbiota-associated chloride channels participated in colon
tumorigenesis. CONCLUSION: Gut microbiota changes occur in the hyperproliferative
stage before tumor formation. Gut microbiota and host chloride channels, both of
which are regulated by dietary factors, are associated with CRC development.
PMID- 29331104
TI - Inhibition of mircoRNA-34a Enhances Survival of Human Bone Marrow Mesenchymal
Stromal/Stem Cells Under Oxidative Stress.
AB - BACKGROUND Mesenchymal stromal/stem cells (MSCs) are broadly used for many
diseases, but the efficacy of MSC engraftment is very low due to low viability
and high cell death rate under a stressful microenvironment. The present study
aimed to investigate whether microRNA-34a (miR-34a), which is a downstream target
of P53, is involved in H2O2-induced MSC cell death. MATERIAL AND METHODS Human
bone marrow MSCs (hMSCs) were purchased from Lonza and were cultured as
previously described. hMSCs were transfected with miR-34a inhibitor and exposed
to H2O2. Cell proliferation assay was used to assess the survival rate of hMSCs.
Real-time PCR and Western blot analysis were used to examine proliferation and
survival ability of hMSCs. RESULTS H2O2 exposure significantly increased miR-34a
expression in human bone marrow MSCs. H2O2 challenge induced massive MSC cell
death along with reduction of expression of proliferation marker Ki67 and
survival-related genes Bcl-2 and Survivin. Transfection of miR-34a inhibitor anti
34a led to a significant protective effect and rescued MSC cell death triggered
by H2O2 exposure by 50%. Moreover, anti-34a dramatically increased Bcl-2 and Ki67
mRNA expression levels by over 10-fold compared to the mock control group under
H2O2 exposure. The protein levels of Bcl-2 and Survivin were also rescued by anti
34a treatment by 50%. CONCLUSIONS Our results suggest that miR-34a plays a key
role in oxidative stress-induced MSC cell death, and targeting miR-34a might be a
promising strategy to enhance the survival rate of engrafted stem cells, which
may improve therapeutic outcome.
PMID- 29331106
TI - Kbtbd2 inhibits the cytotoxic activity of immortalized NK cells through down
regulating mTOR signaling in a mouse hepatocellular carcinoma model.
AB - Natural killer cell (NK cell)-based immunotherapy is a promising therapeutic
strategy for hepatocellular carcinoma (HCC). However, the molecular mechanisms
underlying the regulation of NK cell function in the tumor sites are not
completely elucidated. In this study, we identified the enhanced expression of
kelch repeat and BTB (POZ) domain containing 2 (Kbtbd2) in intratumoral NK cells
in a mouse HCC implantation model as a negative regulator of NK cells. To
investigate this interaction, we used a Tet-on inducible expression system to
control Kbtbd2 expression in an immortalized mouse NK cell line KIL C.2. With
this approach, we found that overexpression of Kbtbd2 reduced KIL C.2 cell
proliferation, decreased expression certain of Ly49 receptor family members, and
substantially impaired cytotoxic activity of KIL C.2 cells in vitro. Moreover,
phosphorylation of mTOR and its target 4E-binding protein 1 was reduced in Kbtbd2
expressing KIL C.2 cells, along with down-regulated phosphorylation of Erk1/2.
Adoptively transferred Kbtbd2-expressing KIL C.2 cells exhibited weaker
tumoricidal effect on hepatocellular carcinoma cells in the HCC implantation
model, in comparison with transferred control KIL C.2 cells. Taken together, our
investigation indicates that Kbtbd2 is an inhibitory molecule for the tumoricidal
activity of KIL C.2 cells and perhaps intratumoral NK cells.
PMID- 29331107
TI - Endoscopic Full-Thickness Resection Combined with Laparoscopic Surgery.
AB - Endoscopic full-thickness resection combined with laparoscopic surgery was
recently developed. These procedures could be categorized as "Cut first and then
suture" and "Suture first and then cut". "Cut first and then suture" includes
laparoscopic and endoscopic cooperative surgery (LECS) and laparoscopy-assisted
endoscopic full-thickness resection (LAEFR). Recent studies have demonstrated the
safety and efficacy of LECS and LAEFR. However, these techniques are limited by
the related exposure of the tumor and gastric mucosa to the peritoneal cavity and
manipulation of these organs, which could lead to viable cancer cell seeding and
the spillage of gastric juice into the peritoneal cavity. In the "Suture first
and then cut" technique, the serosal side of the stomach is sutured to invert the
stomach and subsequently endoscopic resection is performed. In this article,
details of these techniques, including their advantages and limitations, are
described.
PMID- 29331108
TI - Classical molecular dynamics simulation of microwave heating of liquids: The case
of water.
AB - We perform a complete classical molecular dynamics study of the dielectric
heating of water in the microwave (MW) region. MW frequencies ranging from 1.0 to
15.0 GHz are used together with a series of well-known empirical force fields. We
show that the ability of an empirical force field to correctly predict the
dielectric response of liquids to MW radiation should be evaluated on the basis
of a joint comparison of the predicted and experimental static dielectric
constant, frequency-dependent dielectric spectra, and heating profiles. We argue
that this is essential when multicomponent liquids are studied. We find that both
the three-site OPC3 and four-site TIP4P-epsilon empirical force fields of water
are equally superior for reproducing dielectric properties at a range of MW
frequencies. Despite its poor prediction of the static dielectric constant, the
well-known SPCE force field can be used to accurately describe dielectric heating
of water at low MW frequencies.
PMID- 29331109
TI - Interaction of C2H with molecular hydrogen: Ab initio potential energy surface
and scattering calculations.
AB - The potential energy surface (PES) describing the interaction of the ethynyl
(C2H) radical in its ground X2Sigma+ electronic state with molecular hydrogen has
been computed through restricted coupled cluster calculations including single,
double, and (perturbative) triple excitations [RCCSD(T)], with the assumption of
fixed molecular geometries. The computed points were fit to an analytical form
suitable for time-independent quantum scattering calculations of rotationally
inelastic cross sections and rate constants. A representative set of energy
dependent state-to-state cross sections is presented and discussed. The PES and
cross sections for collisions of H2(j = 0) are compared with a previous study [F.
Najar et al., Chem. Phys. Lett. 614, 251 (2014)] of collisions of C2H with H2
treated as a spherical collision partner. Good agreement is found between the two
sets of calculations when the H2 molecule in the present calculation is
spherically averaged.
PMID- 29331110
TI - Random sequential adsorption of cubes.
AB - Random packings built of cubes are studied numerically using a random sequential
adsorption algorithm. To compare the obtained results with previous reports,
three different models of cube orientation sampling were used. Also, three
different cube-cube intersection algorithms were tested to find the most
efficient one. The study focuses on the mean saturated packing fraction as well
as kinetics of packing growth. Microstructural properties of packings were
analyzed using density autocorrelation function.
PMID- 29331111
TI - "Star" morphologies of charged nanodrops comprised of conformational isomers.
AB - We study the spatial distribution of conformational isomers surrounding a central
macroion in a charged droplet with linear dimensions in the nanometer range.
Dimethyl carbonate and formic acid are selected as typical solvents that undergo
isomerization and a charged buckyball (C60) is selected as a representative
example of a macroion. The study is performed by atomistic molecular dynamics
simulations. We find that when the charge of the buckyball is above a threshold
value, it induces the formation of concentric shells of different conformational
isomers surrounding the macroion. The presence of layers with different
dielectric properties necessitates the use of different state equations for the
solvent polarization in each layer. We find that at a high charge state of the
buckyball, the nearest layer to the macroion comprises the conformers with the
highest dipole moment. The interface of the outer layers of conformers is
characterized by "ray"-forming structures of the higher dielectric constant
isomers penetrating into the layer of the lowest dielectric constant isomers. For
high values of the solvent dielectric constant, the charged droplet acquires a
"star"-like global shape. We demonstrate that these distinct droplet structures
are a manifestation of charge-induced instability. We describe this simulation
based phenomenology by an analytical theory that supports this conclusion. The
findings suggest new experimental research venues that may explore the reactivity
and assembly of molecules within regions of different dielectric properties in
droplets.
PMID- 29331112
TI - Effects of dispersion interactions on the structure, polarity, and dynamics of
liquid-vapor interface of an aqueous NaCl solution: Results of first principles
simulations at room temperature.
AB - The effects of dispersion interaction on the structure, polarity, and dynamics of
liquid-vapor interface of a concentrated (5.3M) aqueous NaCl solution have been
investigated through first-principles simulations. Among the structural
properties, we have investigated the inhomogeneous density profiles of molecules,
hydrogen bond distributions, and orientational profiles. On the dynamical side,
we have calculated diffusion, orientational relaxation, hydrogen bond dynamics,
and vibrational spectral diffusion of molecules. The polarity of water molecules
across the interface is also calculated. Our simulation results are compared with
those when no dispersion corrections are included. It is found that the inclusion
of dispersion correction predicts an overall improvement of the structural
properties of liquid water. The current study reveals a faster relaxation of
hydrogen bonds, diffusion, and rotational motion for both interfacial and bulk
molecules compared to the results when no such dispersion corrections are
included. The dynamics of vibrational frequency fluctuations are also calculated
which capture the relaxation of hydrogen bond fluctuations in the bulk and
interfacial regions. Generally, the hydrogen bonds at the interfaces are found to
have longer lifetimes due to reduced cooperative effects.
PMID- 29331114
TI - Hartree-Fock symmetry breaking around conical intersections.
AB - We study the behavior of Hartree-Fock (HF) solutions in the vicinity of conical
intersections. These are here understood as regions of a molecular potential
energy surface characterized by degenerate or nearly degenerate eigenfunctions
with identical quantum numbers (point group, spin, and electron numbers).
Accidental degeneracies between states with different quantum numbers are known
to induce symmetry breaking in HF. The most common closed-shell restricted HF
instability is related to singlet-triplet spin degeneracies that lead to
collinear unrestricted HF solutions. Adding geometric frustration to the mix
usually results in noncollinear generalized HF (GHF) solutions, identified by
orbitals that are linear combinations of up and down spins. Near conical
intersections, we observe the appearance of coplanar GHF solutions that break all
symmetries, including complex conjugation and time-reversal, which do not carry
good quantum numbers. We discuss several prototypical examples taken from the
conical intersection literature. Additionally, we utilize a recently introduced
magnetization diagnostic to characterize these solutions, as well as a solution
of a Jahn-Teller active geometry of H8+2.
PMID- 29331113
TI - Uniform magnetic fields in density-functional theory.
AB - We construct a density-functional formalism adapted to uniform external magnetic
fields that is intermediate between conventional density functional theory and
Current-Density Functional Theory (CDFT). In the intermediate theory, which we
term linear vector potential-DFT (LDFT), the basic variables are the density, the
canonical momentum, and the paramagnetic contribution to the magnetic moment.
Both a constrained-search formulation and a convex formulation in terms of
Legendre-Fenchel transformations are constructed. Many theoretical issues in CDFT
find simplified analogs in LDFT. We prove results concerning N-representability,
Hohenberg-Kohn-like mappings, existence of minimizers in the constrained-search
expression, and a restricted analog to gauge invariance. The issue of additivity
of the energy over non-interacting subsystems, which is qualitatively different
in LDFT and CDFT, is also discussed.
PMID- 29331115
TI - Theoretical analysis of the domain-swapped dimerization of cytochrome c: An MD
and 3D-RISM approach.
AB - The structural stability of a cytochrome c domain-swapped dimer compared with
that of the monomer was investigated by molecular dynamics (MD) simulations and
by three-dimensional reference interaction site model (3D-RISM) theory. The
structural fluctuation and structural energy of cytochrome c were treated by MD
simulations, and the solvation thermodynamics was treated by 3D-RISM theory. The
domain-swapped dimer state is slightly less stable than the monomer state, which
is consistent with experimental observations; the total free energy difference is
calculated as 25 kcal mol-1. The conformational change and
translational/rotational entropy change contribute to the destabilization of the
dimer, whereas the hydration and vibrational entropy contribute to the
stabilization. Further analyses on the residues located at the hinge loop for
swapping were conducted, and the results reveal details at the molecular level of
the structural and interaction changes upon dimerization.
PMID- 29331116
TI - Tensor-decomposed vibrational coupled-cluster theory: Enabling large-scale,
highly accurate vibrational-structure calculations.
AB - A new implementation of vibrational coupled-cluster (VCC) theory is presented,
where all amplitude tensors are represented in the canonical polyadic (CP)
format. The CP-VCC algorithm solves the non-linear VCC equations without ever
constructing the amplitudes or error vectors in full dimension but still formally
includes the full parameter space of the VCC[n] model in question resulting in
the same vibrational energies as the conventional method. In a previous
publication, we have described the non-linear-equation solver for CP-VCC
calculations. In this work, we discuss the general algorithm for evaluating VCC
error vectors in CP format including the rank-reduction methods used during the
summation of the many terms in the VCC amplitude equations. Benchmark
calculations for studying the computational scaling and memory usage of the CP
VCC algorithm are performed on a set of molecules including thiadiazole and an
array of polycyclic aromatic hydrocarbons. The results show that the reduced
scaling and memory requirements of the CP-VCC algorithm allows for performing
high-order VCC calculations on systems with up to 66 vibrational modes
(anthracene), which indeed are not possible using the conventional VCC method.
This paves the way for obtaining highly accurate vibrational spectra and
properties of larger molecules.
PMID- 29331117
TI - Accurate virial coefficients of gaseous krypton from state-of-the-art ab initio
potential and polarizability of the krypton dimer.
AB - We have developed a new krypton-krypton interaction-induced isotropic dipole
polarizability curve based on high-level ab initio methods. The determination was
carried out using the coupled-cluster singles and doubles plus perturbative
triples method with very large basis sets up to augmented correlation-consistent
sextuple zeta as well as the corrections for core-core and core-valence
correlation and relativistic effects. The analytical function of polarizability
and our recently constructed reference interatomic potential [J. M. Waldrop et
al., J. Chem. Phys. 142, 204307 (2015)] were used to predict the thermophysical
and electromagnetic properties of krypton gas. The second pressure, acoustic, and
dielectric virial coefficients were computed for the temperature range of 116 K
5000 K using classical statistical mechanics supplemented with high-order quantum
corrections. The virial coefficients calculated were compared with the generally
less precise available experimental data as well as with values computed from
other potentials in the literature {in particular, the recent highly accurate
potential of Jager et al. [J. Chem. Phys. 144, 114304 (2016)]}. The detailed
examination in this work suggests that the present theoretical prediction can be
applied as reference values in disciplines involving thermophysical and
electromagnetic properties of krypton gas.
PMID- 29331118
TI - Exploration of near the origin and the asymptotic behaviors of the Kohn-Sham
kinetic energy density for two-dimensional quantum dot systems with parabolic
confinement.
AB - The behaviors of the positive definite Kohn-Sham kinetic energy density near the
origin and at the asymptotic region play a major role in designing meta
generalized gradient approximations (meta-GGAs) for exchange in low-dimensional
quantum systems. It is shown that near the origin of the parabolic quantum dot,
the Kohn-Sham kinetic energy differs from its von Weizsacker counterpart due to
the p orbital contributions, whereas in the asymptotic region, the difference
between the above two kinetic energy densities goes as ~rho(r)r2. All these
behaviors have been explored using the two-dimensional isotropic quantum harmonic
oscillator as a test case. Several meta-GGA ingredients are then studied by
making use of the above findings. Also, the asymptotic conditions for the
exchange energy density and the potential at the meta-GGA level are proposed
using the corresponding behaviors of the two kinetic energy densities.
PMID- 29331119
TI - Molecular dynamics investigation of water-exchange reactions on lanthanide ions
in water/1-ethyl-3-methylimidazolium trifluoromethylsufate ([EMIm][OTf]).
AB - We report a kinetic study of the water exchange on lanthanide ions in water/[1
ethyl-3-methylimidazolium][trifluoromethylsufate] (water/[EMIm][OTf]). The
results from 17O-NMR measurements show that the water-exchange rates in
water/[EMIm][OTf] increase with decreasing size of the lanthanide ions. This
trend for water-exchange is similar to the previously reported trend in water/1
ethyl-3-methylimidazolium ethyl sulfate (water/[EMIm][EtSO4]) but opposite to
that in water. To gain atomic-level insight into these water-exchange reactions,
molecular dynamics simulations for lanthanide ions in water/[EMIm][OTf] have been
performed using the atomic-multipole-optimized-energetics-for-biomolecular
application polarizable force field. Our molecular dynamics simulations reproduce
the experimental water-exchange rates in terms of the trend and provide possible
explanations for the observed experimental behavior. The smaller lanthanide ions
in water/[EMIm][OTf] undergo faster water exchange because the smaller lanthanide
ions coordinate to the first shell [OTf]- anions more tightly, resulting in a
stronger screening effect for the second-shell water. The screening effect
weakens the interaction of the lanthanide ions with the second-shell water
molecules, facilitating the dissociation of water from the second-shell and
subsequent association of water molecules from the outer solvation shells.
PMID- 29331120
TI - On the mechanical stability of the body-centered cubic phase and the emergence of
a metastable cI16 phase in classical hard sphere solids.
AB - The stability of the body-centered cubic (bcc) solid phase of classical hard
spheres is of intrinsic interest and is also relevant to the development of
perturbation theories for bcc solids of other model systems. Using canonical
ensemble Monte Carlo, we simulated systems initialized in a perfect bcc lattice
at various densities in the solid region. We observed that the systems rapidly
evolved into one of four structures that then persisted for the duration of the
simulation. Remarkably, one of these structures was identified as cI16, a cubic
crystalline structure with 16 particles in the unit cell, which has recently been
observed experimentally in lithium and sodium solids at high pressures. The other
three structures do not exhibit crystalline order but are characterized by common
patterns in the radial distribution function and bond-orientational order
parameter distribution; we refer to them as bcc-di, with i ranging from 1 to 3.
We found similar outcomes when employing any of the three single occupancy cell
(SOC) restrictions commonly used in the literature. We also ran long constant
pressure simulations with box shape fluctuations initiated from bcc and cI16
initial configurations. At lower pressures, all the systems evolved to defective
face-centered cubic (fcc) or hexagonal close-packed (hcp) structures. At higher
pressures, most of the systems initiated as bcc evolved to cI16 with some
evolving to defective fcc/hcp. High pressure systems initiated from cI16 remained
in that structure. We computed the chemical potential of cI16 using the Einstein
crystal reference method and found that it is higher than that of fcc by ~0.5kT
2.5kT over the pressure range studied, with the difference increasing with
pressure. We find that the undistorted bcc solid, even with constant-volume and
SOC restrictions applied, is so mechanically unstable that it is unsuitable for
consideration as a metastable phase or as a reference system for studying bcc
phases of other systems. On the other hand, cI16 is a mechanically stable
structure that can spontaneously emerge from a bcc starting point but it is
thermodynamically metastable relative to fcc or hcp.
PMID- 29331121
TI - Diffusion of a particle in the spatially correlated exponential random energy
landscape: Transition from normal to anomalous diffusion.
AB - Diffusive transport of a particle in a spatially correlated random energy
landscape having exponential density of states has been considered. We exactly
calculate the diffusivity in the nondispersive quasi-equilibrium transport regime
for the 1D transport model and found that for slow decaying correlation functions
the diffusivity becomes singular at some particular temperature higher than the
temperature of the transition to the true non-equilibrium dispersive transport
regime. It means that the diffusion becomes anomalous and does not follow the
usual ? t1/2 law. In such situation, the fully developed non-equilibrium regime
emerges in two stages: first, at some temperature there is the transition from
the normal to anomalous diffusion, and then at lower temperature the average
velocity for the infinite medium goes to zero, thus indicating the development of
the true dispersive regime. Validity of the Einstein relation is discussed for
the situation where the diffusivity does exist. We provide also some arguments in
favor of conservation of the major features of the new transition scenario in
higher dimensions.
PMID- 29331122
TI - Thermally induced charge current through long molecules.
AB - In this work, we theoretically study steady state thermoelectric transport
through a single-molecule junction with a long chain-like bridge. Electron
transmission through the system is computed using a tight-binding model for the
bridge. We analyze dependences of thermocurrent on the bridge length in unbiased
and biased systems operating within and beyond the linear response regime. It is
shown that the length-dependent thermocurrent is controlled by the lineshape of
electron transmission in the interval corresponding to the HOMO/LUMO transport
channel. Also, it is demonstrated that electron interactions with molecular
vibrations may significantly affect the length-dependent thermocurrent.
PMID- 29331123
TI - The influence of ion hydration on nucleation and growth of LiF crystals in
aqueous solution.
AB - Molecular dynamics (MD) simulations are employed to investigate crystal
nucleation and growth in oversaturated aqueous LiF solutions. Results obtained
for a range of temperatures provide evidence that the rate of crystal growth is
determined by a substantial energy barrier (~49 kJ mol-1) related to the loss of
water from the ion hydration shells. Employing direct MD simulations, we do not
observe spontaneous nucleation of LiF crystals at 300 K, but nucleation is easily
observable in NVT simulations at 500 K. This contrasts with the NaCl case, where
crystal nucleation is directly observed in similar simulations at 300 K. Based on
these observations, together with a detailed analysis of ion clustering in
metastable LiF solutions, we argue that the ion dehydration barrier also plays a
key role in crystal nucleation. The hydration of the relatively small Li+ and F-
ions strongly influences the probability of forming large, crystal-like ion
clusters, which are a necessary precursor to nucleation. This important factor is
not accounted for in classical nucleation theory.
PMID- 29331124
TI - Characterizing protein conformations by correlation analysis of coarse-grained
contact matrices.
AB - We have developed a method to capture the essential conformational dynamics of
folded biopolymers using statistical analysis of coarse-grained segment-segment
contacts. Previously, the residue-residue contact analysis of simulation
trajectories was successfully applied to the detection of conformational
switching motions in biomolecular complexes. However, the application to large
protein systems (larger than 1000 amino acid residues) is challenging using the
description of residue contacts. Also, the residue-based method cannot be used to
compare proteins with different sequences. To expand the scope of the method, we
have tested several coarse-graining schemes that group a collection of
consecutive residues into a segment. The definition of these segments may be
derived from structural and sequence information, while the interaction strength
of the coarse-grained segment-segment contacts is a function of the residue
residue contacts. We then perform covariance calculations on these coarse-grained
contact matrices. We monitored how well the principal components of the contact
matrices is preserved using various rendering functions. The new method was
demonstrated to assist the reduction of the degrees of freedom for describing the
conformation space, and it potentially allows for the analysis of a system that
is approximately tenfold larger compared with the corresponding residue contact
based method. This method can also render a family of similar proteins into the
same conformational space, and thus can be used to compare the structures of
proteins with different sequences.
PMID- 29331125
TI - Diffusion-influenced reaction rates for active "sphere-prolate spheroid" pairs
and Janus dimers.
AB - The purpose of this paper is twofold. First, we provide a concise introduction to
the generalized method of separation of variables for solving diffusion problems
in canonical domains beyond conventional arrays of spheres. Second, as an
important example of its application in the theory of diffusion-influenced
reactions, we present an exact solution of the axially symmetric problem on
diffusive competition in an array of two active particles (including Janus
dumbbells) constructed of a prolate spheroid and a sphere. In particular, we
investigate how the reaction rate depends on sizes of active particles, spheroid
aspect ratio, particles' surface reactivity, and distance between their centers.
PMID- 29331126
TI - Binding branched and linear DNA structures: From isolated clusters to fully
bonded gels.
AB - The proper design of DNA sequences allows for the formation of well-defined
supramolecular units with controlled interactions via a consecution of self
assembling processes. Here, we benefit from the controlled DNA self-assembly to
experimentally realize particles with well-defined valence, namely, tetravalent
nanostars (A) and bivalent chains (B). We specifically focus on the case in which
A particles can only bind to B particles, via appropriately designed sticky-end
sequences. Hence AA and BB bonds are not allowed. Such a binary mixture system
reproduces with DNA-based particles the physics of poly-functional condensation,
with an exquisite control over the bonding process, tuned by the ratio, r,
between B and A units and by the temperature, T. We report dynamic light
scattering experiments in a window of Ts ranging from 10 degrees C to 55
degrees C and an interval of r around the percolation transition to quantify the
decay of the density correlation for the different cases. At low T, when all
possible bonds are formed, the system behaves as a fully bonded network, as a
percolating gel, and as a cluster fluid depending on the selected r.
PMID- 29331127
TI - Molecular hydrodynamics: Vortex formation and sound wave propagation.
AB - In the present study, quantitative feasibility tests of the hydrodynamic
description of a two-dimensional fluid at the molecular level are performed, both
with respect to length and time scales. Using high-resolution fluid velocity data
obtained from extensive molecular dynamics simulations, we computed the
transverse and longitudinal components of the velocity field by the Helmholtz
decomposition and compared them with those obtained from the linearized Navier
Stokes (LNS) equations with time-dependent transport coefficients. By
investigating the vortex dynamics and the sound wave propagation in terms of
these field components, we confirm the validity of the LNS description for times
comparable to or larger than several mean collision times. The LNS description
still reproduces the transverse velocity field accurately at smaller times, but
it fails to predict characteristic patterns of molecular origin visible in the
longitudinal velocity field. Based on these observations, we validate the main
assumptions of the mode-coupling approach. The assumption that the velocity
autocorrelation function can be expressed in terms of the fluid velocity field
and the tagged particle distribution is found to be remarkably accurate even for
times comparable to or smaller than the mean collision time. This suggests that
the hydrodynamic-mode description remains valid down to the molecular scale.
PMID- 29331128
TI - Two-component Gaussian core model: Strong-coupling limit, Bjerrum pairs, and gas
liquid phase transition.
AB - In the present work, we investigate a gas-liquid transition in a two-component
Gaussian core model, where particles of the same species repel and those of
different species attract. Unlike a similar transition in a one-component system
with particles having attractive interactions at long separations and repulsive
interactions at short separations, a transition in the two-component system is
not driven solely by interactions but by a specific feature of the interactions,
the correlations. This leads to extremely low critical temperature, as
correlations are dominant in the strong-coupling limit. By carrying out various
approximations based on standard liquid-state methods, we show that a gas-liquid
transition of the two-component system poses a challenging theoretical problem.
PMID- 29331129
TI - Perspective: Structural fluctuation of protein and Anfinsen's thermodynamic
hypothesis.
AB - The thermodynamics hypothesis, casually referred to as "Anfinsen's dogma," is
described theoretically in terms of a concept of the structural fluctuation of
protein or the first moment (average structure) and the second moment (variance
and covariance) of the structural distribution. The new theoretical concept views
the unfolding and refolding processes of protein as a shift of the structural
distribution induced by a thermodynamic perturbation, with the variance
covariance matrix varying. Based on the theoretical concept, a method to
characterize the mechanism of folding (or unfolding) is proposed. The transition
state, if any, between two stable states is interpreted as a gap in the
distribution, which is created due to an extensive reorganization of hydrogen
bonds among back-bone atoms of protein and with water molecules in the course of
conformational change. Further perspective to applying the theory to the computer
aided drug design, and to the material science, is briefly discussed.
PMID- 29331130
TI - Femtosecond coherent nuclear dynamics of excited tetraphenylethylene: Ultrafast
transient absorption and ultrafast Raman loss spectroscopic studies.
AB - Ultrafast torsional dynamics plays an important role in the photoinduced excited
state dynamics. Tetraphenylethylene (TPE), a model system for the molecular
motor, executes interesting torsional dynamics upon photoexcitation. The
photoreaction of TPE involves ultrafast internal conversion via a nearly planar
intermediate state (relaxed state) that further leads to a twisted zwitterionic
state. Here, we report the photoinduced structural dynamics of excited TPE during
the course of photoisomerization in the condensed phase by ultrafast Raman loss
(URLS) and femtosecond transient absorption (TA) spectroscopy. TA measurements on
the S1 state reveal step-wise population relaxation from the Franck-Condon (FC)
state -> relaxed state -> twisted state, while the URLS study provides insights
on the vibrational dynamics during the course of the reaction. The TA spectral
dynamics and vibrational Raman amplitudes within 1 ps reveal vibrational wave
packet propagating from the FC state to the relaxed state. Fourier transformation
of this oscillation leads to a ~130 cm-1 low-frequency phenyl torsional mode. Two
vibrational marker bands, Cet=Cet stretching (~1512 cm-1) and Cph=Cph stretching
(~1584 cm-1) modes, appear immediately after photoexcitation in the URLS spectra.
The initial red-shift of the Cph=Cph stretching mode with a time constant of ~400
fs (in butyronitrile) is assigned to the rate of planarization of excited TPE. In
addition, the Cet=Cet stretching mode shows initial blue-shift within 1 ps
followed by frequency red-shift, suggesting that on the sub-picosecond time
scale, structural relaxation is dominated by phenyl torsion rather than the
central Cet=Cet twist. Furthermore, the effect of the solvent on the structural
dynamics is discussed in the context of ultrafast nuclear dynamics and solute
solvent coupling.
PMID- 29331131
TI - Combining the ensemble and Franck-Condon approaches for calculating spectral
shapes of molecules in solution.
AB - The correct treatment of vibronic effects is vital for the modeling of absorption
spectra of many solvated dyes. Vibronic spectra for small dyes in solution can be
easily computed within the Franck-Condon approximation using an implicit solvent
model. However, implicit solvent models neglect specific solute-solvent
interactions on the electronic excited state. On the other hand, a
straightforward way to account for solute-solvent interactions and temperature
dependent broadening is by computing vertical excitation energies obtained from
an ensemble of solute-solvent conformations. Ensemble approaches usually do not
account for vibronic transitions and thus often produce spectral shapes in poor
agreement with experiment. We address these shortcomings by combining zero
temperature vibronic fine structure with vertical excitations computed for a room
temperature ensemble of solute-solvent configurations. In this combined approach,
all temperature-dependent broadening is treated classically through the sampling
of configurations and quantum mechanical vibronic contributions are included as a
zero-temperature correction to each vertical transition. In our calculation of
the vertical excitations, significant regions of the solvent environment are
treated fully quantum mechanically to account for solute-solvent polarization and
charge-transfer. For the Franck-Condon calculations, a small amount of frozen
explicit solvent is considered in order to capture solvent effects on the
vibronic shape function. We test the proposed method by comparing calculated and
experimental absorption spectra of Nile red and the green fluorescent protein
chromophore in polar and non-polar solvents. For systems with strong solute
solvent interactions, the combined approach yields significant improvements over
the ensemble approach. For systems with weak to moderate solute-solvent
interactions, both the high-energy vibronic tail and the width of the spectra are
in excellent agreement with experiments.
PMID- 29331132
TI - Detection and characterization of the tin dihydride (SnH2 and SnD2) molecule in
the gas phase.
AB - The SnH2 and SnD2 molecules have been detected for the first time in the gas
phase by laser-induced fluorescence (LIF) and emission spectroscopic techniques
through the A1B1-X1A1 electronic transition. These reactive species were prepared
in a pulsed electric discharge jet using (CH3)4Sn or SnH4/SnD4 precursors diluted
in high pressure argon. Transitions to the electronic excited state of the jet
cooled molecules were probed with LIF, and the ground state energy levels were
measured from single rovibronic level emission spectra. The LIF spectrum of SnD2
afforded sufficient rotational structure to determine the ground and excited
state geometries: r0" = 1.768 A, theta0" = 91.0 degrees , r0' = 1.729 A, theta0'
= 122.9 degrees . All of the observed LIF bands show evidence of a rotational
level-dependent predissociation process which rapidly decreases the fluorescence
yield and lifetime with increasing rotational angular momentum in each excited
vibronic level. This behavior is analogous to that observed in SiH2 and GeH2 and
is suggested to lead to the formation of ground state tin atoms and hydrogen
molecules.
PMID- 29331133
TI - The effect of Pd ensemble structure on the O2 dissociation and CO oxidation
mechanisms on Au-Pd(100) surface alloys.
AB - The reactivity of various Pd ensembles on the Au-Pd(100) alloy catalyst toward CO
oxidation was investigated by using density functional theory (DFT). This study
was prompted by the search for efficient catalysts operating at low temperature
for the CO oxidation reaction that is of primary environmental importance. To
this aim, we considered Pd modified Au(100) surfaces including Pd monomers, Pd
dimers, second neighboring Pd atoms, and Pd chains in a comparative study of the
minimum energy reaction pathways. The effect of dispersion interactions was
included in the calculations of the O2 dissociation reaction pathway by using the
DFT-D3 scheme. The addition of the dispersion interaction strongly improves the
adsorption ability of O2 on the Au-Pd surface but does not affect the activation
energy barriers of the Transitions States (TSs). As for O2 to dissociate, it is
imperative that the TS has lower activation energy than the O2 desorption energy.
DFT-D3 is found to favor, in some cases, O2 dissociation on configurations being
identified from uncorrected DFT calculations as inactive. This is the case of the
second neighboring Pd configuration for which uncorrected DFT predicts positive
Gibbs free energy (DeltaG) of the O2 adsorption, therefore an endergonic
reaction. With the addition of D3 correction, DeltaG becomes negative that
reveals a spontaneous O2 adsorption. Among the investigated Au-Pd (100)
ensembles, the Pd chain dissociates most easily O2 and highly stabilizes the
dissociated O atoms; however, it has an inferior reactivity toward CO oxidation
and CO2 formation. Indeed, CO strongly adsorbs on the palladium bridge sites and
therefore poisoning the surface Pd chain. By contrast, the second neighboring Pd
configuration that shows somewhat lower ability to dissociate O2 turns out to be
more reactive in the CO2 formation step. These results evidence the complex
effect of Pd ensembles on the CO oxidation reaction. Associative CO oxidation
proceeds with high energy barriers on all the considered Pd ensembles and should
be excluded, in agreement with experimental observations.
PMID- 29331134
TI - Coarse-grained model of nanoscale segregation, water diffusion, and proton
transport in Nafion membranes.
AB - We present a coarse-grained model of the acid form of Nafion membrane that
explicitly includes proton transport. This model is based on a soft-core bead
representation of the polymer implemented into the dissipative particle dynamics
(DPD) simulation framework. The proton is introduced as a separate charged bead
that forms dissociable Morse bonds with water beads. Morse bond formation and
breakup artificially mimics the Grotthuss hopping mechanism of proton transport.
The proposed DPD model is parameterized to account for the specifics of the
conformations and flexibility of the Nafion backbone and sidechains; it treats
electrostatic interactions in the smeared charge approximation. The simulation
results qualitatively, and in many respects quantitatively, predict the specifics
of nanoscale segregation in the hydrated Nafion membrane into hydrophobic and
hydrophilic subphases, water diffusion, and proton mobility. As the hydration
level increases, the hydrophilic subphase exhibits a percolation transition from
a collection of isolated water clusters to a 3D network of pores filled with
water embedded in the hydrophobic matrix. The segregated morphology is
characterized in terms of the pore size distribution with the average size
growing with hydration from ~1 to ~4 nm. Comparison of the predicted water
diffusivity with the experimental data taken from different sources shows good
agreement at high and moderate hydration and substantial deviation at low
hydration, around and below the percolation threshold. This discrepancy is
attributed to the dynamic percolation effects of formation and rupture of merging
bridges between the water clusters, which become progressively important at low
hydration, when the coarse-grained model is unable to mimic the fine structure of
water network that includes singe molecule bridges. Selected simulations of water
diffusion are performed for the alkali metal substituted membrane which
demonstrate the effects of the counter-ions on membrane self-assembly and
transport. The hydration dependence of the proton diffusivity reproduces semi
qualitatively the trend of the diverse experimental data, showing a sharp
decrease around the percolation threshold. Overall, the proposed model opens up
an opportunity to study self-assembly and water and proton transport in
polyelectrolytes using computationally efficient DPD simulations, and, with
further refinement, it may become a practical tool for theory informed design and
optimization of perm-selective and ion-conducting membranes with improved
properties.
PMID- 29331135
TI - Erratum: "Communication: Molecular near-infrared transitions determined with sub
kHz accuracy" [J. Chem. Phys. 147, 091103 (2017)].
PMID- 29331136
TI - Zwitterionization of glycine in water environment: Stabilization mechanism and
NMR spectral signatures.
AB - At physiological conditions, myriads of biomolecules (e.g., amino acids,
peptides, and proteins) exist predominantly in the zwitterionic structural form
and their biological functions will result in these conditions. However these
geometrical structures are inaccessible energetically in the gas phase, and at
this point, stabilization of amino-acids in physiological conditions is still
under debate. In this paper, the electronic properties of a glycine molecule in
the liquid environment were studied by performing a relaxation of the glycine
geometry in liquid water using the free energy gradient method combined with a
sequential quantum mechanics/molecular mechanics approach. A series of Monte
Carlo Metropolis simulations of the glycine molecule embedded in liquid water,
followed by only a quantum mechanical calculation in each of them were carried
out. Both the local and global liquid environments were emphasized to obtain
nuclear magnetic resonance (NMR) parameters for the glycine molecule in liquid
water. The results of the equilibrium structure in solution and the systematic
study of the hydrogen bonds were used to discard the direct proton transfer from
the carboxyl group to the ammonium group of the glycine molecule in water
solution. The calculations of the Density Functional Theory (DFT) were performed
to study the polarization of the solvent in the parameters of nuclear magnetic
resonance of the glycine molecule in liquid water. DFT calculations predicted
isotropic chemical changes on the H, C, N, and O atoms of glycine in liquid water
solution which agree with the available experimental data.
PMID- 29331137
TI - Molecular dynamics based enhanced sampling of collective variables with very
large time steps.
AB - Enhanced sampling techniques that target a set of collective variables and that
use molecular dynamics as the driving engine have seen widespread application in
the computational molecular sciences as a means to explore the free-energy
landscapes of complex systems. The use of molecular dynamics as the fundamental
driver of the sampling requires the introduction of a time step whose magnitude
is limited by the fastest motions in a system. While standard multiple time
stepping methods allow larger time steps to be employed for the slower and
computationally more expensive forces, the maximum achievable increase in time
step is limited by resonance phenomena, which inextricably couple fast and slow
motions. Recently, we introduced deterministic and stochastic resonance-free
multiple time step algorithms for molecular dynamics that solve this resonance
problem and allow ten- to twenty-fold gains in the large time step compared to
standard multiple time step algorithms [P. Minary et al., Phys. Rev. Lett. 93,
150201 (2004); B. Leimkuhler et al., Mol. Phys. 111, 3579-3594 (2013)]. These
methods are based on the imposition of isokinetic constraints that couple the
physical system to Nose-Hoover chains or Nose-Hoover Langevin schemes. In this
paper, we show how to adapt these methods for collective variable-based enhanced
sampling techniques, specifically adiabatic free-energy dynamics/temperature
accelerated molecular dynamics, unified free-energy dynamics, and by extension,
metadynamics, thus allowing simulations employing these methods to employ
similarly very large time steps. The combination of resonance-free multiple time
step integrators with free-energy-based enhanced sampling significantly improves
the efficiency of conformational exploration.
PMID- 29331139
TI - Non-iterative triple excitations in equation-of-motion coupled-cluster theory for
electron attachment with applications to bound and temporary anions.
AB - The impact of residual electron correlation beyond the equation-of-motion coupled
cluster singles and doubles (EOM-CCSD) approximation on positions and widths of
electronic resonances is investigated. To establish a method that accomplishes
this task in an economical manner, several approaches proposed for the
approximate treatment of triple excitations are reviewed with respect to their
performance in the electron attachment (EA) variant of EOM-CC theory. The
recently introduced EOM-CCSD(T)(a)* method [D. A. Matthews and J. F. Stanton, J.
Chem. Phys. 145, 124102 (2016)], which includes non-iterative corrections to the
reference and the target states, reliably reproduces vertical attachment energies
from EOM-EA-CC calculations with single, double, and full triple excitations in
contrast to schemes in which non-iterative corrections are applied only to the
target states. Applications of EOM-EA-CCSD(T)(a)* augmented by a complex
absorbing potential (CAP) to several temporary anions illustrate that shape
resonances are well described by EOM-EA-CCSD, but that residual electron
correlation often makes a non-negligible impact on their positions and widths.
The positions of Feshbach resonances, on the other hand, are significantly
improved when going from CAP-EOM-EA-CCSD to CAP-EOM-EA-CCSD(T)(a)*, but the
correct energetic order of the relevant electronic states is still not achieved.
PMID- 29331138
TI - Role of non-equilibrium conformations on driven polymer translocation.
AB - One of the major theoretical methods in understanding polymer translocation
through a nanopore is the Fokker-Planck formalism based on the assumption of
quasi-equilibrium of polymer conformations. The criterion for applicability of
the quasi-equilibrium approximation for polymer translocation is that the average
translocation time per Kuhn segment, ?tau?/NK, is longer than the relaxation time
tau0 of the polymer. Toward an understanding of conditions that would satisfy
this criterion, we have performed coarse-grained three dimensional Langevin
dynamics and multi-particle collision dynamics simulations. We have studied the
role of initial conformations of a polyelectrolyte chain (which were artificially
generated with a flow field) on the kinetics of its translocation across a
nanopore under the action of an externally applied transmembrane voltage V (in
the absence of the initial flow field). Stretched (out-of-equilibrium)
polyelectrolyte chain conformations are deliberately and systematically generated
and used as initial conformations in translocation simulations. Independent
simulations are performed to study the relaxation behavior of these stretched
chains, and a comparison is made between the relaxation time scale and the mean
translocation time (?tau?). For such artificially stretched initial states,
?tau?/NK < tau0, demonstrating the inapplicability of the quasi-equilibrium
approximation. Nevertheless, we observe a scaling of ?tau? ~ 1/V over the entire
range of chain stretching studied, in agreement with the predictions of the
Fokker-Planck model. On the other hand, for realistic situations where the
initial artificially imposed flow field is absent, a comparison of experimental
data reported in the literature with the theory of polyelectrolyte dynamics
reveals that the Zimm relaxation time (tauZimm) is shorter than the mean
translocation time for several polymers including single stranded DNA (ssDNA),
double stranded DNA (dsDNA), and synthetic polymers. Even when these data are
rescaled assuming a constant effective velocity of translocation, it is found
that for flexible (ssDNA and synthetic) polymers with NK Kuhn segments, the
condition ?tau?/NK < tauZimm is satisfied. We predict that for flexible polymers
such as ssDNA, a crossover from quasi-equilibrium to non-equilibrium behavior
would occur at NK ~ O(1000).
PMID- 29331140
TI - Erratum: "An automated nudged elastic band method" [J. Chem. Phys. 145, 094107
(2016)].
PMID- 29331141
TI - Effects of cross-linking on partitioning of nanoparticles into a polymer brush:
Coarse-grained simulations test simple approximate theories.
AB - The effect of cohesive contacts or, equivalently, dynamical cross-linking on the
equilibrium morphology of a polymer brush infiltrated by nanoparticles that are
attracted to the polymer strands is studied for plane-grafted brushes using
coarse-grained molecular dynamics and approximate statistical mechanical models.
In particular, the Alexander-de Gennes (AdG) and Strong Stretching Theory (SST)
mean-field theory (MFT) models are considered. It is found that for values of the
MFT cross-link strength interaction parameter beyond a certain threshold, both
AdG and SST models predict that the polymer brush will be in a compact state of
nearly uniform density packed next to the grafting surface over a wide range of
solution phase nanoparticle concentrations. Coarse grained molecular dynamics
simulations confirm this prediction, for both small nanoparticles (nanoparticle
volume = monomer volume) and large nanoparticles (nanoparticle volume = 27 *
monomer volume). Simulation results for these cross-linked systems are compared
with analogous results for systems with no cross-linking. At the same solution
phase nanoparticle concentration, strong cross-linking results in additional
compression of the brush relative to the non-crosslinked analog and, at all but
the lowest concentrations, to a lesser degree of infiltration by nanoparticles.
For large nanoparticles, the monomer density profiles show clear oscillations
moving outwards from the grafting surface, corresponding to a degree of layering
of the absorbed nanoparticles in the brush as they pack against the grafting
surface.
PMID- 29331142
TI - Kinetic step-growth polymerization: A dissipative particle dynamics simulation
study.
AB - Kinetic step-growth polymerization is studied by dissipative particle dynamics
coupled with our previously developed reaction algorithm on a coarse-grained
level. The simulation result proves that this step-growth polymerization obeys
the second-order reaction kinetics. We apply this algorithm to study the step
growth polymerization using the subunits with different flexibilities or within
confinement. Good agreement of the number fraction distributions with the Flory
distribution is obtained, implying that this algorithm is reasonable to describe
such a kind of step-growth polymerization. This algorithm can further supply a
convenient platform for simulating typical step-growth polymerization in reactive
polymer systems.
PMID- 29331143
TI - Effects of system size and cooling rate on the structure and properties of sodium
borosilicate glasses from molecular dynamics simulations.
AB - Borosilicate glasses form an important glass forming system in both glass science
and technologies. The structure and property changes of borosilicate glasses as a
function of thermal history in terms of cooling rate during glass formation and
simulation system sizes used in classical molecular dynamics (MD) simulation were
investigated with recently developed composition dependent partial charge
potentials. Short and medium range structural features such as boron
coordination, Si and B Qn distributions, and ring size distributions were
analyzed to elucidate the effects of cooling rate and simulation system size on
these structure features and selected glass properties such as glass transition
temperature, vibration density of states, and mechanical properties. Neutron
structure factors, neutron broadened pair distribution functions, and vibrational
density of states were calculated and compared with results from experiments as
well as ab initio calculations to validate the structure models. The results
clearly indicate that both cooling rate and system size play an important role on
the structures of these glasses, mainly by affecting the 3B and 4B distributions
and consequently properties of the glasses. It was also found that different
structure features and properties converge at different sizes or cooling rates;
thus convergence tests are needed in simulations of the borosilicate glasses
depending on the targeted properties. The results also shed light on the complex
thermal history dependence on structure and properties in borosilicate glasses
and the protocols in MD simulations of these and other glass materials.
PMID- 29331144
TI - Communication: Site-selective bond excision of adenine upon electron transfer.
AB - This work demonstrates that selective excision of hydrogen atoms at a particular
site of the DNA base adenine can be achieved in collisions with electronegative
atoms by controlling the impact energy. The result is based on analysing the time
of-flight mass spectra yields of potassium collisions with a series of labeled
adenine derivatives. The production of dehydrogenated parent anions is consistent
with neutral H loss either from selective breaking of C-H or N-H bonds. These
unprecedented results open up a new methodology in charge transfer collisions
that can initiate selective reactivity as a key process in chemical reactions
that are dominant in different areas of science and technology.
PMID- 29331145
TI - Modelling the effect of acoustic waves on the thermodynamics and kinetics of
phase transformation in a solution: Including mass transportation.
AB - Effects of acoustic waves on a phase transformation in a metastable phase were
investigated in our previous work [S. R. Haqshenas, I. J. Ford, and N. Saffari,
"Modelling the effect of acoustic waves on nucleation," J. Chem. Phys. 145,
024315 (2016)]. We developed a non-equimolar dividing surface cluster model and
employed it to determine the thermodynamics and kinetics of crystallisation
induced by an acoustic field in a mass-conserved system. In the present work, we
developed a master equation based on a hybrid Szilard-Fokker-Planck model, which
accounts for mass transportation due to acoustic waves. This model can determine
the kinetics of nucleation and the early stage of growth of clusters including
the Ostwald ripening phenomenon. It was solved numerically to calculate the
kinetics of an isothermal sonocrystallisation process in a system with mass
transportation. The simulation results show that the effect of mass
transportation for different excitations depends on the waveform as well as the
imposed boundary conditions and tends to be noticeable in the case of shock
waves. The derivations are generic and can be used with any acoustic source and
waveform.
PMID- 29331146
TI - Publisher's Note: "The Landau-de Gennes approach revisited: A minimal self
consistent microscopic theory for spatially inhomogeneous nematic liquid
crystals" [J. Chem. Phys. 147, 244505 (2017)].
PMID- 29331147
TI - Direct variational determination of the two-electron reduced density matrix for
doubly occupied-configuration-interaction wave functions: The influence of three
index N-representability conditions.
AB - This work proposes the variational determination of two-electron reduced density
matrices corresponding to the ground state of N-electron systems within the
doubly occupied-configuration-interaction methodology. The P, Q, and G two-index
N-representability conditions have been extended to the T1 and T2 (T2') three
index ones and the resulting optimization problem has been addressed using a
standard semidefinite program. We report results obtained from the doubly
occupied-configuration-interaction method, from the two-index constraint
variational procedure and from the two- and three-index constraint variational
treatment. The discussion of these results along with a study of the
computational cost demanded shows the usefulness of our proposal.
PMID- 29331148
TI - Isolation of anti-extra-cellular vesicle single-domain antibodies by direct
panning on vesicle-enriched fractions.
AB - BACKGROUND: The thorough understanding of the physiological and pathological
processes mediated by extracellular vesicles (EVs) is challenged by purification
methods which are cumbersome, not reproducible, or insufficient to yield
homogeneous material. Chromatography based on both ion-exchange and immune
capture can represent an effective method to improve EV purification and
successive analysis. METHODS: Cell culture supernatant was used as a model sample
for assessing the capacity of anion-exchange chromatography to separate distinct
EV fractions and to isolate nanobodies by direct panning on whole EVs to recover
binders specific for the native conformation of EV-surface epitopes and suitable
to develop EV immune-capture reagents. RESULTS: Anion-exchange chromatography of
cell culture supernatant separated distinct protein-containing fractions and all
of them were positive for CD9, a biomarker associated to some EVs. This suggested
the existence of several EV fractions but did not help in separating EVs from
other contaminants. We further isolated several nanobodies instrumental for
implementing immune-affinity protocols. These were able to immobilize EVs from
both cell culture supernatant and biological samples, to be used in ELISA, flow
cytometry, and immune-purification. CONCLUSIONS: Here we report the first
successful isolation of anti-EV nanobodies for the use in immunoaffinity-based EV
capture by panning a phage library directly on partially purified EVs. This
achievement paves the way for the application of direct EV panning for the
discovery of novel antibody-vesicle surface biomarker pairs and represents the
preliminary requirement for the development of selective immune-capture that, in
combination with anion-exchange chromatography, can simplify the systematic
stratification of EV sub-populations and their individual characterization.
PMID- 29331149
TI - Correction to: Entrapment of an EGFR inhibitor into nanostructured lipid carriers
(NLC) improves its antitumor activity against human hepatocarcinoma cells.
AB - Following publication of our article [1], we became aware that Roberto Di Gesu
had been omitted from the list of authors. The corrected author list and authors'
contribution statement appear below. We apologize for any inconvenience this may
have caused.
PMID- 29331150
TI - Production of eicosapentaenoic acid by application of a delta-6 desaturase with
the highest ALA catalytic activity in algae.
AB - : Dunaliella salina is a unicellular green alga with a high alpha-linolenic acid
(ALA) level, but a low eicosapentaenoic acid (EPA) level. In a previous analysis
of the catalytic activity of delta 6 fatty acid desaturase (FADS6) from various
species, FADS6 from Thalassiosira pseudonana (TpFADS6), a marine diatom, showed
the highest catalytic activity for ALA. In this study, to enhance EPA production
in D. salina, FADS6 from D. salina (DsFADS6) was identified, and substrate
specificities for DsFADS6 and TpFADS6 were characterized. Furthermore, a plasmid
harboring the TpFADS6 gene was constructed and overexpressed in D. salina. Our
results revealed that EPA production reached 21.3 +/- 1.5 mg/L in D. salina
transformants. To further increase EPA production, myoinositol (MI) was used as a
growth-promoting agent; it increased the dry cell weight of D. salina
transformants, and EPA production reached 91.3 +/- 11.6 mg/L. The combination of
12% CO2 aeration with glucose/KNO3 in the medium improved EPA production to 192.9
+/- 25.7 mg/L in the Ds-TpFADS6 transformant. We confirmed that the increase in
ALA was optimal at 8 degrees C; the EPA percentage reached 41.12 +/- 4.78%. The
EPA yield was further increased to 554.3 +/- 95.6 mg/L by supplementation with 4
g/L perilla seed meal (PeSM), 500 mg/L MI, and 12% CO2 aeration with glucose/KNO3
at varying temperatures. EPA production and the percentage of EPA in D. salina
were 343.8-fold and 25-fold higher than those in wild-type D. salina,
respectively. IMPORTANCE: FADS6 from Thalassiosira pseudonana, which demonstrates
high catalytic activity toward alpha-linolenic acid, was used to enhance EPA
production by Dunaliella salina. Transformation of FADS6 from Thalassiosira
pseudonana into Dunaliella salina with myoinositol, CO2, low temperatures, and
perilla seed meal supplementation substantially increased EPA production in
Dunaliella salina to 554.3 +/- 95.6 mg/L. Accordingly, D. salina could be a
potential alternative source of EPA and is suitable for its large-scale
production.
PMID- 29331151
TI - The impact of parental mental illness across the full diagnostic spectrum on
externalising and internalising vulnerabilities in young offspring.
AB - BACKGROUND: The intergenerational risk for mental illness is well established
within diagnostic categories, but the risk is unlikely to respect diagnostic
boundaries and may be reflected more broadly in early life vulnerabilities. We
aimed to establish patterns of association between externalising and
internalising vulnerabilities in early childhood and parental mental disorder
across the full spectrum of diagnoses. METHODS: A cohort of Australian children
(n = 69 116) entering the first year of school in 2009 were assessed using the
Australian Early Development Census, providing measures of externalising and
internalising vulnerability. Parental psychiatric diagnostic status was
determined utilising record-linkage to administrative health datasets. RESULTS:
Parental mental illness, across diagnostic categories, was associated with all
child externalising and internalising domains of vulnerability. There was little
evidence to support interaction by parental or offspring sex. CONCLUSIONS: These
findings have important implications for informing early identification and
intervention strategies in high-risk offspring and for research into the causes
of mental illness. There may be benefits to focusing less on diagnostic
categories in both cases.
PMID- 29331152
TI - Functioning before and after a major depressive episode: pre-existing
vulnerability or scar? A prospective three-wave population-based study.
AB - BACKGROUND: The vulnerability hypothesis suggests that impairments after
remission of depressive episodes reflect a pre-existing vulnerability, while the
scar hypothesis proposes that depression leaves residual impairments that confer
risk of subsequent episodes. We prospectively examined vulnerability and scar
effects in mental and physical functioning in a representative Dutch population
sample. METHODS: Three waves were used from the Netherlands Mental Health Survey
and Incidence Study-2, a population-based study with a 6-years follow-up. Mental
and physical functioning were assessed with the Medical Outcomes Study Short Form
(SF-36). Major depressive disorder (MDD) was assessed with the Composite
International Diagnostic Interview 3.0. Vulnerability effects were examined by
comparing healthy controls (n = 2826) with individuals who developed a first
onset depressive episode during first follow-up but did not have a lifetime
diagnosis of MDD at baseline (n = 181). Scarring effects were examined by
comparing pre- and post-morbid functioning in individuals who developed a
depressive episode after baseline that was remitted at the third wave (n = 108).
RESULTS: Both mental (B = -5.4, s.e. = 0.9, p < 0.001) and physical functioning
(B = -8.2, s.e. = 1.1, p < 0.001) at baseline were lower in individuals who
developed a first depressive episode after baseline compared with healthy
controls. This effect was most pronounced in people who developed a severe
episode. No firm evidence of scarring in mental or physical functioning was
found. In unadjusted analyses, physical functioning was still lowered post
morbidly (B = -5.1, s.e. = 2.1, p = 0.014), but this effect disappeared in
adjusted analyses. CONCLUSIONS: Functional impairments after remission of
depression seem to reflect a pre-existing vulnerability rather than a scar.
PMID- 29331153
TI - Is cognitive impairment associated with antipsychotic dose and anticholinergic
equivalent loads in first-episode psychosis?
AB - BACKGROUND: Cognitive deficits are a core feature of early stages in
schizophrenia. However, the extent to which antipsychotic (AP) have a deleterious
effect on cognitive performance remains under debate. We aim to investigate
whether anticholinergic loadings and dose of AP drugs in first episode of
psychosis (FEP) in advanced phase of remission are associated with cognitive
impairment and the differences between premorbid intellectual quotient (IQ)
subgroups. METHODS: Two hundred and sixty-six patients participated. The primary
outcomes were cognitive dimensions, dopaminergic/anticholinergic load of AP [in
chlorpromazine equivalents (Eq-CPZ) and the Anticholinergic Risk Scale (ARS),
respectively]. RESULTS: Impairments in processing speed, verbal memory and global
cognition were significantly associated with high Eq-CPZ and verbal impairment
with high ARS score. Moreover, this effect was higher in the low IQ subgroup.
CONCLUSIONS: Clinicians should be aware of the potential cognitive impairment
associated with AP in advanced remission FEP, particularly in lower premorbid IQ
patients.
PMID- 29331154
TI - Predicting Multidrug-Resistant Gram-Negative Bacterial Colonization and
Associated Infection on Hospital Admission: Methodological Issues.
PMID- 29331155
TI - Performance of a Novel Antipseudomonal Antibiotic Consumption Metric Among
Academic Medical Centers in the United States.
AB - A metric was developed to identify hospital proportion of carbapenem consumption
(PoCC) among antipseudomonal antibiotics. The PoCC varied significantly among
academic medical centers by Census Bureau geographic division after adjusting for
patient mix. This metric may be useful in identifying disproportionate carbapenem
use and potential carbapenem overuse. Infect Control Hosp Epidemiol 2018;39:229
232.
PMID- 29331156
TI - High Hand Contamination Rates During Norovirus Outbreaks in Long-Term Care
Facilities.
AB - We examined norovirus contamination on hands of ill patients during 12 norovirus
outbreaks in 12 long-term care facilities (LTCFs). The higher frequency and
norovirus titers on hands of residents compared to hands of heathcare workers
highlights the importance of adhering to appropriate hand hygiene practices
during norovirus outbreaks in LTCFs. Infect Control Hosp Epidemiol 2018;39:219
221.
PMID- 29331157
TI - Eccentric placentae have reduced surface area and are associated with lower birth
weight in babies small for gestational age.
AB - Placental structure and function determine birth outcomes. Placental mass does
not always correlate with fetal birth weight (BW) in uncomplicated pregnancies
which raises the possibility of other variables such as placental shape and cord
insertion being the determinants of placental efficiency. In total, 160 women
with singleton pregnancy, recruited into a pregnancy cohort were studied.
Placental weight (PW) was measured and other data were obtained from clinical
records. Birth outcomes were classified as small for gestational age (SGA) and
appropriate for gestational age (AGA) based on fetal gender, gestational age (GA)
and BW. High-resolution images of the chorionic plate were recorded. The shape of
the placenta and the insertion of the cord were measured using eccentricity index
(EI) and cord centrality index (CCI). Only placentae with eccentrically inserted
cords (n=136) were included. The mean BW and PW were 2942 (+/-435) g and 414 (+/
82) g with average GA of 38.6 weeks. The mean CCI and EI was 0.483 (+/-0.17) and
0.482 (+/-0.16). Neither of these correlated with placental efficiency. However,
EI showed negative correlation with placental surface area and breadth. Upon sub
grouping the cohort into SGA (n=32) and AGA (n=104), the SGA babies with the
highest EI (third tertile) had significantly lower BW than those with the least
eccentric placentae (first tertile). Although eccentric-shaped placentae were
present in both SGA and AGA groups, the effect on BW was observed only in the SGA
group.
PMID- 29331158
TI - Dietary sources of energy and nutrients in the contemporary diet of Inuit adults:
results from the 2007-08 Inuit Health Survey.
AB - OBJECTIVE: To characterize the major components of the contemporary Inuit diet
and identify the primary sources of energy and essential nutrients. DESIGN:
Dietary data were derived from the 24 h recall collected by the Inuit Health
Survey (IHS) from 2007 to 2008. The population proportion method was used to
determine the percentage contribution of each group. Unique food
items/preparations (ninety-three country foods and 1591 market foods) were
classified into eight country food groups and forty-one market food groups.
Nutrient composition of each food item was obtained from the Canadian Nutrient
File. SETTING: Thirty-six communities across three Inuit regions of northern
Canada. SUBJECTS: A representative sample (n 2095) of non-pregnant Inuit adults
(>=18 years), selected through stratified random sampling. RESULTS: Despite their
modest contribution to total energy intake (6.4-19.6 %, by region) country foods
represented a major source of protein (23-52 %), Fe (28-54 %), niacin (24-52 %)
and vitamins D (up to 73 %), B6 (18-55 %) and B12 (50-82 %). By contrast, the
three most popular energy-yielding market foods (i.e. sweetened beverages, added
sugar and bread) collectively contributed approximately 20 % of total energy,
while contributing minimally to most micronutrients. A notable exception was the
contribution of these foods to Ca (13-21 %) and vitamins E (17-35 %) and C (as
much as 50 %). Solid fruits were consumed by less than 25 % of participants while
vegetables were reported by 38-59 % of respondents. CONCLUSIONS: Country foods
remain a critical dimension of the contemporary Inuit diet.
PMID- 29331159
TI - Diagnostic Stewardship for Healthcare-Associated Infections: Opportunities and
Challenges to Safely Reduce Test Use.
PMID- 29331160
TI - Reduction in Rate of Nosocomial Respiratory Virus Infections in a Children's
Hospital Associated With Enhanced Isolation Precautions.
AB - OBJECTIVE To determine whether the use of enhanced isolation precautions (droplet
and contact precautions) for inpatients with respiratory tract viral infections
is associated with a reduction in rate of nosocomial viral respiratory
infections. DESIGN Quasi-experimental study with the rate of nosocomial
respiratory virus infection as the primary dependent variable and rate of
nosocomial Clostridium difficile infection as a nonequivalent dependent variable
comparator. SETTING Cohen Children's Medical Center of NY, a tertiary-care
children's hospital attached to a large general hospital. INTERVENTION During
years 1 and 2 (July 2012 through June 2014), the Centers for Disease Control and
Prevention/Healthcare Infection Control Practices Advisory Committee's
recommended isolation precautions for inpatients with selected respiratory virus
infections were in effect. Enhanced isolation precautions were in effect during
years 3 and 4 (July, 2014 through June, 2016), except for influenza, for which
enhanced precautions were in effect during year 4 only. RESULTS During the period
of enhanced isolation precautions, the rate of nosocomial respiratory virus
infections with any of 4 virus categories decreased 39% from 0.827 per 1,000
hospital days prior to enhanced precautions to 0.508 per 1,000 hospital days
(P<.0013). Excluding rhinovirus/enterovirus infections, the rates decreased 58%
from 0.317 per 1,000 hospital days to 0.134 per 1,000 hospital days during
enhanced precautions (P<.0014). During these periods, no significant change was
detected in the rate of nosocomial C. difficile infection. CONCLUSIONS Enhanced
isolation precautions for inpatients with respiratory virus infections were
associated with a reduction in the rate of nosocomial respiratory virus
infections. Infect Control Hosp Epidemiol 2018;39:152-156.
PMID- 29331161
TI - Hormone therapy, gender affirmation surgery, and their association with recent
suicidal ideation and depression symptoms in transgender veterans.
AB - BACKGROUND: Access to transition-related medical interventions (TRMIs) for
transgender veterans has been the subject of substantial public interest and
debate. To better inform these important conversations, the current study
investigated whether undergoing hormone or surgical transition intervention(s)
relates to the frequency of recent suicidal ideation (SI) and symptoms of
depression in transgender veterans. METHODS: This study included a cross
sectional, national sample of 206 self-identified transgender veterans. They self
reported basic demographics, TRMI history, recent SI, and symptoms of depression
through an online survey. RESULTS: Significantly lower levels of SI experienced
in the past year and 2-weeks were seen in veterans with a history of both hormone
intervention and surgery on both the chest and genitals in comparison with those
who endorsed a history of no medical intervention, history of hormone therapy but
no surgical intervention, and those with a history of hormone therapy and surgery
on either (but not both) the chest or genitals when controlling for sample
demographics (e.g., gender identity and annual income). Indirect effect analyses
indicated that lower depressive symptoms experienced in the last 2-weeks mediated
the relationship between the history of surgery on both chest and genitals and SI
in the last 2-weeks. CONCLUSIONS: Results indicate the potential protective
effect that TRMI may have on symptoms of depression and SI in transgender
veterans, particularly when both genitals and chest are affirmed with one's
gender identity. Implications for policymakers, providers, and researchers are
discussed.
PMID- 29331162
TI - Unnecessary Removal of Central Venous Catheters in Cancer Patients with
Bloodstream Infections.
AB - We evaluated the rate of central venous catheter (CVC) removal in 283 cancer
patients with bloodstream infections (BSIs). Removal of CVCs occurred
unnecessarily in 57% of patients with non-central-line-associated BSI (non
CLABSI), which was equivalent to the rate of CVC removal in patients with
CLABSIs. Physician education and safe interventions to salvage the vascular
access are warranted. Infect Control Hosp Epidemiol 2018;39:222-225.
PMID- 29331163
TI - Healthcare Personnel Relationships Related to Coordination of Catheter Care.
PMID- 29331164
TI - Adherence to the Danish food-based dietary guidelines and risk of myocardial
infarction: a cohort study.
AB - OBJECTIVE: A direct way to evaluate food-based dietary guidelines is to assess if
adherence is associated with development of non-communicable diseases. Thus, the
objective was to develop an index to assess adherence to the 2013 Danish food
based dietary guidelines and to investigate the association between adherence to
the index and risk of myocardial infarction (MI). DESIGN: Population-based cohort
study with recruitment of participants in 1993-1997. Information on dietary
intake was collected at baseline using an FFQ and an index ranging from 0 to 6
points was created to assess adherence to the 2013 Danish food-based dietary
guidelines. MI cases were identified by record linkage to the Danish National
Patient Register and the Causes of Death Register. Cox proportional hazards
models were used to estimate hazard ratios (HR) of MI. SETTING: Greater areas of
Aarhus and Copenhagen, Denmark. SUBJECTS: Men and women aged 50-64 years (n 55
021) from the Diet, Cancer and Health study. RESULTS: A total of 3046
participants were diagnosed with first-time MI during a median follow-up of 16.9
years. A higher Danish Dietary Guidelines Index score was associated with a lower
risk of MI. After adjustment for potential confounders, the hazard of MI was 13 %
lower among men with a score of 3-<4 (HR=0.87; 95 % CI 0.78, 0.96) compared with
men with a score of <3. The corresponding HR among women was 0.76 (95 % CI 0.63,
0.93). CONCLUSIONS: Adherence to the 2013 Danish food-based dietary guidelines
was inversely associated with risk of MI.
PMID- 29331165
TI - Investigating the population structure and genetic differentiation of livestock
guard dog breeds.
AB - Livestock guarding dogs are a valuable adjunct to the pastoral community. Having
been traditionally selected for their working ability, they fulfil their function
with minimal interaction or command from their human owners. In this study, the
population structure and the genetic differentiation of three Italian livestock
guardian breeds (Sila's Dog, Maremma and Abruzzese Sheepdog and Mannara's Dog)
and three functionally and physically similar breeds (Cane Corso, Central Asian
Shepherd Dog and Caucasian Shepherd Dog), totalling 179 dogs unrelated at the
second generation, were investigated with 18 autosomal microsatellite markers.
Values for the number of alleles per locus, observed and expected heterozygosity,
Hardy-Weinberg Equilibrium, F stats, Nei's and Reynold's genetic distances,
clustering and sub-population formation abilities and individual genetic
structures were calculated. Our results show clear breed differentiation, whereby
all the considered breeds show reasonable genetic variability despite small
population sizes and variable selection schemes. These results provide meaningful
data to stakeholders in specific breed and environmental conservation programmes.
PMID- 29331166
TI - Institution-wide and Within-Patient Evolution of Daptomycin Susceptibility in
Vancomycin-Resistant Enterococcus faecium Bloodstream Infections.
AB - We report daptomycin minimum inhibitory concentrations (MICs) for vancomycin
resistant Enterococcus faecium isolated from bloodstream infections over a 4-year
period. The daptomycin MIC increased over time hospital-wide for initial isolates
and increased over time within patients, culminating in 40% of patients having
daptomycin-nonsusceptible isolates in the final year of the study. Infect Control
Hosp Epidemiol 2018;39:226-228.
PMID- 29331167
TI - The association between psychotic experiences and traumatic life events: the role
of the intention to harm.
AB - BACKGROUND: Previous work showed traumatic life events (TLE) with intention to
harm, like bullying and abuse, to be more strongly associated with psychotic
experiences (PE) than other types of trauma, like accidents. However, this
association is subject to reporting bias and can be confounded by demographic
characteristics and by differences in dose of exposure across different trauma
categories. We studied the association between TLE with and without intention to
harm and PE, taking into account potential confounders and biases. METHODS: A
total of 2245 children and adolescents aged 6-14 years were interviewed by
psychologists. The interview included the presence of 20 PE (both self-report and
psychologist evaluation). In addition, parents provided information on child
exposure to trauma, mental health and PE. RESULTS: Results showed no significant
association between TLE without intention to harm only and PE for the three
methods of assessment of PE (self-report, parent report and psychologist rating).
On the other hand, there was a positive association between PE and TLE in groups
exposed to traumatic experiences with intention to harm (with intention to harm
only and with and without intention to harm). Results remained significant after
controlling for demographic and clinical confounders, but this positive
association was no longer significant after adjusting for the number of TLE.
CONCLUSIONS: TLE with intention to harm display a stronger association with PE
than TLE without intention to harm, and this difference is likely reducible to a
greater level of traumatic exposure associated with TLE with intention to harm.
PMID- 29331168
TI - Dietary patterns and their associations with home food availability among Finnish
pre-school children: a cross-sectional study.
AB - OBJECTIVE: To study the associations between home food availability and dietary
patterns among pre-school children. DESIGN: Cross-sectional study in which
parents of the participating children filled in an FFQ and reported how often
they had certain foods in their homes. We derived dietary pattern scores using
principal component analysis, and composite scores describing the availability of
fruits and vegetables as well as sugar-enriched foods in the home were created
for each participant. We used multilevel models to investigate the associations
between availability and dietary pattern scores. SETTING: The DAGIS study,
Finland. SUBJECTS: The participants were 864 Finnish 3-6-year-old children
recruited from sixty-six pre-schools. The analyses included 711 children with
sufficient data. RESULTS: We identified three dietary patterns explaining 16.7 %
of the variance. The patterns were named 'sweets-and-treats' (high loadings of
e.g. sweet biscuits, chocolate, ice cream), 'health-conscious' (high loadings of
e.g. nuts, natural yoghurt, berries) and 'vegetables-and-processed meats' (high
loadings of e.g. vegetables, cold cuts, fruit). In multivariate models, the
availability of fruits and vegetables was inversely associated with the sweets
and-treats pattern (beta=-0.05, P<0.01) and positively associated with the health
conscious (beta=0.07, P<0.01) and vegetables-and-processed meats patterns
(beta=0.06, P<0.01). The availability of sugar-enriched foods was positively
associated with the sweets-and-treats pattern (beta=0.10, P<0.01) and inversely
associated with the health-conscious pattern (beta=-0.03, P<0.01). CONCLUSIONS:
Considering dietary patterns, the availability of sugar-enriched foods in the
home seems to have a stronger role than that of fruits and vegetables. Parents
should restrict the availability of unhealthy foods in the home.
PMID- 29331169
TI - The introduction of simple cardiorespiratory fitness testing in overweight/obese
type 2 diabetics: a pilot study.
AB - BACKGROUND: Low level of cardiorespiratory fitness has been recognized as an
important independent and modifiable risk factor of increased morbidity and
mortality. However, in standard outpatient settings, patients are not routinely
screened for fitness and advantages of such testing for the management of type 2
diabetes have not been defined.AimTo describe the toleration of a fast, simple
and practicable fitness test (2-min step-in-place test) by overweight/obese type
2 diabetics and their performance indicated by 2-min step-in-place test score
(STS). To study short-term anthropometric, functional and metabolic changes
following the implementation of the test in the selected population. METHODS: A
total of 33 overweight/obese type 2 diabetics underwent, besides routine
examination at the outpatient clinic, the fitness test (group A). Patients were
asked to increase their regular physical activity with focus on walking without
change in diet and chronic medication. Three to four months later, the subjects
were tested again. An identical number of age- and sex-matched obese diabetics
followed in our outpatient clinic (without fitness testing), was randomly
selected from the Hospital Information System (control group B).FindingsAll
patients subjected to fitness testing completed the protocol successfully. STS
score was found to have a considerable range with differences between males and
females at the borderline of statistical significance. The data are compliant
with lower aerobic endurance of obese diabetics compared with healthy population.
Within study period, the tested group presented with improvements in STS
(referring especially to the males) as well as in several laboratory parameters
of glucose and lipid homeostasis, glomerular function and subclinical
inflammation with no reflection in anthropometry. Group B demonstrated no
significant change. In conclusion, 2-min step-in-place test is fast, undemanding
and well-tolerated by patients and personnel. Following its validation based on
cardiopulmonary exercise testing, the test may prove recommendable for screening
or self-monitoring purposes.
PMID- 29331170
TI - Implementation Lessons Learned From the Benefits of Enhanced Terminal Room (BETR)
Disinfection Study: Process and Perceptions of Enhanced Disinfection with
Ultraviolet Disinfection Devices.
AB - OBJECTIVE To summarize and discuss logistic and administrative challenges we
encountered during the Benefits of Enhanced Terminal Room (BETR) Disinfection
Study and lessons learned that are pertinent to future utilization of ultraviolet
(UV) disinfection devices in other hospitals DESIGN Multicenter cluster
randomized trial SETTING AND PARTICIPANTS Nine hospitals in the southeastern
United States METHODS All participating hospitals developed systems to implement
4 different strategies for terminal room disinfection. We measured compliance
with disinfection strategy, barriers to implementation, and perceptions from
nurse managers and environmental services (EVS) supervisors throughout the 28
month trial. RESULTS Implementation of enhanced terminal disinfection with UV
disinfection devices provides unique challenges, including time pressures from
bed control personnel, efficient room identification, negative perceptions from
nurse managers, and discharge volume. In the course of the BETR Disinfection
Study, we utilized several strategies to overcome these barriers: (1)
establishing safety as the priority; (2) improving communication between EVS, bed
control, and hospital administration; (3) ensuring availability of necessary
resources; and (4) tracking and providing feedback on compliance. Using these
strategies, we deployed ultraviolet (UV) disinfection devices in 16,220 (88%) of
18,411 eligible rooms during our trial (median per hospital, 89%; IQR, 86%-92%).
CONCLUSIONS Implementation of enhanced terminal room disinfection strategies
using UV devices requires recognition and mitigation of 2 key barriers: (1)
timely and accurate identification of rooms that would benefit from enhanced
terminal disinfection and (2) overcoming time constraints to allow EVS cleaning
staff sufficient time to properly employ enhanced terminal disinfection methods.
TRIAL REGISTRATION Clinical trials identifier: NCT01579370 Infect Control Hosp
Epidemiol 2018;39:157-163.
PMID- 29331173
TI - Editorial.
PMID- 29331174
TI - Transcatheter tricuspid repair: The knifeless cutting edge.
PMID- 29331171
TI - The genotypic and phenotypic spectrum of MTO1 deficiency.
AB - BACKGROUND: Mitochondrial diseases, a group of multi-systemic disorders often
characterized by tissue-specific phenotypes, are usually progressive and fatal
disorders resulting from defects in oxidative phosphorylation. MTO1
(Mitochondrial tRNA Translation Optimization 1), an evolutionarily conserved
protein expressed in high-energy demand tissues has been linked to human early
onset combined oxidative phosphorylation deficiency associated with hypertrophic
cardiomyopathy, often referred to as combined oxidative phosphorylation
deficiency-10 (COXPD10). MATERIAL AND METHODS: Thirty five cases of MTO1
deficiency were identified and reviewed through international collaboration. The
cases of two female siblings, who presented at 1 and 2years of life with
seizures, global developmental delay, hypotonia, elevated lactate and complex I
and IV deficiency on muscle biopsy but without cardiomyopathy, are presented in
detail. RESULTS: For the description of phenotypic features, the denominator
varies as the literature was insufficient to allow for complete ascertainment of
all data for the 35 cases. An extensive review of all known MTO1 deficiency cases
revealed the most common features at presentation to be lactic acidosis (LA)
(21/34; 62% cases) and hypertrophic cardiomyopathy (15/34; 44% cases). Eventually
lactic acidosis and hypertrophic cardiomyopathy are described in 35/35 (100%) and
27/34 (79%) of patients with MTO1 deficiency, respectively; with global
developmental delay/intellectual disability present in 28/29 (97%), feeding
difficulties in 17/35 (49%), failure to thrive in 12/35 (34%), seizures in 12/35
(34%), optic atrophy in 11/21 (52%) and ataxia in 7/34 (21%). There are 19
different pathogenic MTO1 variants identified in these 35 cases: one splice-site,
3 frameshift and 15 missense variants. None have bi-allelic variants that
completely inactivate MTO1; however, patients where one variant is truncating
(i.e. frameshift) while the second one is a missense appear to have a more
severe, even fatal, phenotype. These data suggest that complete loss of MTO1 is
not viable. A ketogenic diet may have exerted a favourable effect on seizures in
2/5 patients. CONCLUSION: MTO1 deficiency is lethal in some but not all cases,
and a genotype-phenotype relation is suggested. Aside from lactic acidosis and
cardiomyopathy, developmental delay and other phenotypic features affecting
multiple organ systems are often present in these patients, suggesting a broader
spectrum than hitherto reported. The diagnosis should be suspected on clinical
features and the presence of markers of mitochondrial dysfunction in body fluids,
especially low residual complex I, III and IV activity in muscle. Molecular
confirmation is required and targeted genomic testing may be the most efficient
approach. Although subjective clinical improvement was observed in a small number
of patients on therapies such as ketogenic diet and dichloroacetate, no evidence
based effective therapy exists.
PMID- 29331172
TI - Blood phenylalanine reduction corrects CNS dopamine and serotonin deficiencies
and partially improves behavioral performance in adult phenylketonuric mice.
AB - Central nervous system (CNS) deficiencies of the monoamine neurotransmitters
dopamine and serotonin have been implicated in the pathophysiology of
neuropsychiatric dysfunction in human phenylketonuria (PKU). In this study, we
confirmed the occurrence of brain dopamine and serotonin deficiencies in
association with severe behavioral alterations and cognitive impairments in
hyperphenylalaninemic C57BL/6-Pahenu2/enu2 mice, a model of human PKU.
Phenylalanine-reducing treatments, including either dietary phenylalanine
restriction or liver-directed gene therapy, initiated during adulthood were
associated with increased brain monoamine content along with improvements in
nesting behavior but without a change in the severe cognitive deficits exhibited
by these mice. At euthanasia, there was in Pahenu2/enu2 brain a significant
reduction in the protein abundance and maximally stimulated activities of
tyrosine hydroxylase (TH) and tryptophan hydroxylase 2 (TPH2), the rate limiting
enzymes catalyzing neuronal dopamine and serotonin synthesis respectively, in
comparison to levels seen in wild type brain. Phenylalanine-reducing treatments
initiated during adulthood did not affect brain TH or TPH2 content or maximal
activity. Despite this apparent fixed deficit in striatal TH and TPH2 activities,
initiation of phenylalanine-reducing treatments yielded substantial correction of
brain monoamine neurotransmitter content, suggesting that phenylalanine-mediated
competitive inhibition of already constitutively reduced TH and TPH2 activities
is the primary cause of brain monoamine deficiency in Pahenu2 mouse brain. We
propose that CNS monoamine deficiency may be the cause of the partially
reversible adverse behavioral effects associated with chronic HPA in Pahenu2
mice, but that phenylalanine-reducing treatments initiated during adulthood are
unable to correct the neuropathology and attendant cognitive deficits that
develop during juvenile life in late-treated Pahenu2/enu2 mice.
PMID- 29331175
TI - TRACERx: Tracking tumor evolution to impact the course of lung cancer.
PMID- 29331176
TI - Fontan outcomes: Is being educated as good as being wealthy and healthy?
PMID- 29331177
TI - Trans-diaphragmatic chest surgery: Bringing owls to Athens?
PMID- 29331178
TI - Multiple mechanical support modalities and cardiac transplantation in a young
child with corrected transposition.
PMID- 29331179
TI - Surprises happen all the time.
PMID- 29331180
TI - Oh, father, where art we? Left internal mammary artery with greater saphenous
vein grafts still rules surgical coronary revascularization after 30 years.
PMID- 29331181
TI - Play it again...Dr Gibbon.
PMID- 29331182
TI - The long and winding route.
PMID- 29331183
TI - ?
PMID- 29331185
TI - [Patients and caregivers in the treatment of addictions].
AB - Since the 1980s, risk and harm reduction has been a public health issue in the
area of addictions. A new approach has been adopted with drug users, who are
considered as patients like any other and players in their own health care. The
therapeutic alliance with the caregiver is therefore essential.
PMID- 29331184
TI - ?
PMID- 29331186
TI - [Addictology, promoting users' power to act].
AB - The notion of risk reduction applies to all uses, drinking of alcohol and smoking
including, addictions without drugs likewise. With regard to drugs, mentalities
change. We now talk more of risks than fault or deviance. Following,
collaboration between health professionals and users, sharing and cooperation are
the conditions necessary to develop a modern humanist and social addictology
approach.
PMID- 29331187
TI - [Nursing role and risk reduction for drug users].
AB - The Ithaque association is a drop-in and risk reduction centre for drug users. It
caters for anyone 'overwhelmed' by an addiction with a view to supporting them in
the treatment approach they wish to undertake. Nurses play a key role throughout
the user's care pathway.
PMID- 29331188
TI - [Care pathway and life course of drug-addicted patients].
AB - Placing drug addicts, notably heroin addicts, at the centre of their care
project, itself part of a life project, is the objective of the Le Lac d'Argent
association in Annecy. Caregivers have been able to reflect on their practices
and help to fight against preconceived ideas. This article presents the
experience of a global support approach.
PMID- 29331189
TI - [Day clinic, a gateway towards risk reduction].
AB - The addictology day clinic at Fernand-Widal hospital in Paris caters mainly for
patients suffering from alcohol dependence. The aim is to consolidate the
withdrawal which has taken place, to help reduce risks and harm and to support
people waiting for follow-up care.
PMID- 29331190
TI - ?
PMID- 29331191
TI - [An innovative teleconsultation project in liver transplantation].
AB - The Tours and Bourges hospital teams have developed innovative collaborative
practices in the monitoring of patients having received a liver transplant.
Teleconsultation helps the patient resume their normal life by enabling them to
avoid tiring and time-consuming appointments.
PMID- 29331192
TI - [Psychiatry and palliative care, collaboration for the benefit of the patient].
AB - As palliative care units continue to develop, the provision of end-of-life care
for patients with a chronic mental illness needs to be addressed. Aside from the
somatic comorbidities to which these patients are particularly exposed and in
view of the specificity of psychiatric treatment, the forms of end-of-life
support for a patient with schizophrenia are described here, based on the
experience of a psychiatric unit in the Var region.
PMID- 29331193
TI - [Using connected objects to favour patients' adherence to physical activity].
AB - A study explored the factors which can have an impact on the use of connected
objects to improve patients' adherence to physical activity, when they suffer
from chronic low back pain. The results can be used to adjust the development of
an application aimed at patients with chronic low back pain.
PMID- 29331194
TI - [Specificities of nursing care in neurological intensive care].
AB - In the acute phase of the treatment of patients with brain injuries, the
management of secondary brain injuries of systemic origin is a priority. A
neurosurgical intensive care paramedical team shares their experience of the care
delivered and the constant monitoring carried out to optimise, with the medical
team, the patient's outcome and to innovate practices.
PMID- 29331195
TI - [Educational project for raising awareness of food hygiene in infant schools].
AB - Five students from a nursing training institute designed an educational
initiative aimed at infant school pupils. The objective of this primary
prevention intervention was to raise children's awareness of food hygiene.
PMID- 29331196
TI - ?
PMID- 29331197
TI - Talking about the Impact of Screen-viewing on Health.
AB - Emilia is a young woman admitted to the hospital for pyelonephritis. Sophie finds
out, from the morning reports about her, that she stays awake very late every
night watching television or chatting on her mobile phone.
PMID- 29331198
TI - ?
PMID- 29331199
TI - ?
PMID- 29331200
TI - Saliency modulates affective evaluations but not behavioral responses in the
ultimatum game.
AB - Although numerous studies have demonstrated that the saliency of perceptual
information guides attention, the effect of perceptual saliency in high-level
social situations remains unclear. Here, in a modified ultimatum game that
included both gain and loss sharing, we highlighted either the fairness (fair or
unfair) or the valence (gain or loss) aspect of a proposed offer using salient
background colors with social meanings. The results showed that emotional
responses to proposed offers were influenced by visual saliency. Specifically,
individuals felt more dissatisfied about unfair (as opposed to fair) offers when
fairness was emphasized than when valence was emphasized or no emphasis; and
similarly, individuals felt more dissatisfied about loss situations compared to
gain situations when valence was emphasized than when fairness was emphasized or
no emphasis. However, this attentional modulation of social information led to
changes only on affective responses but not on actual behavioral responses. Our
findings indicate that attentional modulation of social information has a
profound impact on affective evaluation by changing how information is weighed.
PMID- 29331201
TI - Impact of polymer geometry on the interactions of protein-PEG conjugates.
AB - The conjugation of high molecular weight polyethylene glycol (PEG) to an active
pharmaceutical ingredient (API) is an attractive strategy for the modification of
biophysical and biodistribution properties of the API. Indeed, several
therapeutic proteins conjugated to PEG have been safely administered in the
clinic. While there have been studies on the configuration of these conjugates in
solution, investigations on the impact of PEG geometry on protein-PEG conjugate
interactions is limited. In this study, we use dynamic light scattering (DLS),
rheology, and small-angle neutron scattering (SANS) to investigate the
biophysical solution and interaction behavior of a 50kDa Fab protein attached to
either a linear or tetrameric (branched) 40kDa PEG molecule. The hydrodynamic
radii, diffusivity, viscosity and pair distance distribution function (PDDF) were
obtained for the protein-PEG conjugates in solution. An analysis revealed that
interactions between unconjugated proteins were quite attractive, however linear
PEG-protein conjugates exhibited net repulsive interactions, similar to that of
the unconjugated polymer. Tetramer PEG-protein conjugates on the other hand,
exhibited a net weak attractive interaction, indicating a more balanced
distribution of repulsive and attractive interaction states. Further analysis of
the SANS data using geometric models consistent with the PDDF elucidated the
conjugates' equilibrium configuration in solution. Insights gained from
measurements and analysis used here can also be useful in predicting how
conjugate geometries affect viscosity and aggregation behavior, which are
important in determining suitable protein-polymer drug formulations.
PMID- 29331202
TI - New anesthetic considerations in thoracic surgery.
PMID- 29331203
TI - Have we forgotten about forgetting? A critical review of 'accelerated long-term
forgetting' in temporal lobe epilepsy.
AB - Forgetting has been researched for over a century. This literature highlighted
how forgetting rates can vary dependent on factors in the design and method.
Recent interest in forgetting revived with evidence suggesting that seizures
experienced almost immediately after matched learning could accelerate
forgetting. This was followed by a growth in forgetting studies in patients with
temporal lobe epilepsy (TLE), including a subset of those with transient
epileptic amnesia (TEA). These patients have been described as expressing
concerns about memory, yet often perform within 'normal' ranges on standard
neuropsychological memory assessments. It was argued that such patients were
experiencing a phenomenon termed 'accelerated long-term forgetting': apparently
normal learning and initial retention with abnormal forgetting over days to weeks
after learning. In this review, we critically evaluate aspects of this
definition, namely whether learning and initial retention is, in fact, 'normal'
at first, and further what this means in relation to 'when' abnormal forgetting
starts. We propose a shift in the understanding of accelerated forgetting in TLE
from an emphasis on late-onset forgetting to greater focus on early-onset,
progressively greater forgetting. We argue that most evidence from studies to
date could be conceptualized within the latter framework, with differences in
forgetting patterns reflective of a continuum of severity and/or sensitivity.
PMID- 29331204
TI - A cognitive model for multidigit number reading: Inferences from individuals with
selective impairments.
AB - We propose a detailed cognitive model of multi-digit number reading. The model
postulates separate processes for visual analysis of the digit string and for
oral production of the verbal number. Within visual analysis, separate sub
processes encode the digit identities and the digit order, and additional sub
processes encode the number's decimal structure: its length, the positions of 0,
and the way it is parsed into triplets (e.g., 314987 -> 314,987). Verbal
production consists of a process that generates the verbal structure of the
number, and another process that retrieves the phonological forms of each number
word. The verbal number structure is first encoded in a tree-like structure,
similarly to syntactic trees of sentences, and then linearized to a sequence of
number-word specifiers. This model is based on an investigation of the number
processing abilities of seven individuals with different selective deficits in
number reading. We report participants with impairment in specific sub-processes
of the visual analysis of digit strings - in encoding the digit order, in
encoding the number length, or in parsing the digit string to triplets. Other
participants were impaired in verbal production, making errors in the number
structure (shifts of digits to another decimal position, e.g., 3,040 -> 30,004).
Their selective deficits yielded several dissociations: first, we found a double
dissociation between visual analysis deficits and verbal production deficits.
Second, several dissociations were found within visual analysis: a double
dissociation between errors in digit order and errors in the number length; a
dissociation between order/length errors and errors in parsing the digit string
into triplets; and a dissociation between the processing of different digits -
impaired order encoding of the digits 2-9, without errors in the 0 position.
Third, within verbal production, a dissociation was found between digit shifts
and substitutions of number words. A selective deficit in any of the processes
described by the model would cause difficulties in number reading, which we
propose to term "dysnumeria".
PMID- 29331205
TI - Free thyroxine and TSH interact with secreted protein acidic and rich in cysteine
like 1 in ischemic stroke.
AB - The role of the thyroid gland in ischemic stroke pathology is not well
understood. As thyroid hormones modulate the extracellular matrix, we explored
the possible link between them and secreted protein acidic and rich in cysteine
like 1 (SC1) - one of the extracellular matrix molecules. In the 81 patients with
acute ischemic stroke, serum SC1 levels were much higher compared with 30 control
subjects: 4.47 vs 2.43ng/mL (p<0.001). Serum levels of free thyroxine (fT4) were
higher in stroke subjects compared to those of controls (p=0.03). In stroke
patients, TSH concentration was lower than in the control group (p=0.03). SC1
levels positively correlated with fT4 levels (p=0.02) and negatively with TSH
(p=0.03) in stroke patients. Our results confirmed the association between
thyroid hormones and SC1 - extracellular matrix protein.
PMID- 29331206
TI - Mechanical thrombectomy: Determining the proportion of eligible acute ischemic
stroke patients in the cohort of single academic stroke center.
AB - BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is now well-established
treatment method for selected patients with acute ischemic stroke (AIS) and
efforts are being made to incorporate it into the systems of stroke care. Our
objective is to assess the number of AIS individuals eligible for MT in the
cohort of single academic stroke center. METHODS: We retrospectively reviewed
initial non-invasive vascular imaging data of AIS patients presenting within 5h
of symptom onset for the presence of large vessel occlusion (LVO) over 2-year
period (2015-2016). Among subjects confirmed with LVO: time-to-presentation,
premorbid functional and on-admission neurological state, site of occlusion and
initial imaging data were further assessed. Two sets of criteria based on recent
trials and recommendations were used to determine MT eligibility. The onset-to
evaluation time limit was set to 5h allowing <=60min procedure initiation delay.
RESULTS: 895 patients with the final diagnosis of AIS were admitted to our stroke
center as the initial treatment facility. 246 (27.5%) presented within 5h of
symptom onset and had non-invasive imaging performed. Among those 102 (41.5%) had
causative LVO. The number of <=5h presenting patients eligible for MT was 51
(20.7%) when applying restrictive or 80 (32.5%) with more permissive criteria.
CONCLUSION: Among AIS patients, in whom onset-to-arrival time allowed to initiate
the endovascular procedure within 6h of symptom duration, 21% were eligible for
MT treatment according to more and 33% to less restrictive criteria. It accounts
for about 6% and 9% of all AIS cases, respectively.
PMID- 29331207
TI - Cerebral amyloid angiopathy-related inflammation - A case report presenting
diagnostic difficulties.
AB - We describe an 86-year-old woman with a history of hypertension who presented
sudden disturbances of consciousness and left hemiparesis. Brain magnetic
resonance imaging (MRI) revealed diffused hyperintensive changes on T2-weighted
images localized subcortically in the white matter of both cerebral hemispheres,
corresponding to acute vasogenic edema, causing moderate mass effect. Posterior
reversible encephalopathy syndrome was initially diagnosed. After implementation
of anti-edema intravenous steroid treatment and hypotensive therapy the symptoms
began to retire, till the total regression. The successive hospitalizations took
place two and eight months later due to the occurrence of seizures, motor
deficits and the development of mild cognitive impairment. Brain MRI revealed
progression of the white matter changes and diffused subcortical
microhemorrhages. Each time pulse steroid therapy was implemented and the
symptoms improved significantly after several days. Chronic oral steroid
treatment resulted in the stabilization of neurological status. The long-term
observation of clinical symptoms, remission after immunosuppressive therapy and
white matter changes with subcortical microhemorrhages in brain MRI leaded to the
diagnosis of cerebral amyloid angiopathy-related inflammation.
PMID- 29331209
TI - Ethical and end of life considerations for neonates requiring ECMO support.
AB - ECMO has proven to be a life-saving intervention for a variety of disease
entities with a high rate of survival in the neonatal population. However, ECMO
requires clinical teams to engage in many ethical considerations. Even with
ongoing improvements in technology and expertise, some patients will not survive
a course of ECMO. An unsuccessful course of ECMO can be difficult to accept and
cause a great deal of angst. These questions can result in real conflict both
within the care team, and between the care team and the family. Herein we explore
a range of ethical considerations that may be encountered when caring for a
patient on ECMO, with a particular focus on those courses where it appears likely
that the patient will not survive. We then consider how a palliative care
approach may provide a tool set to help engage the team and family in confronting
the difficult decision to discontinue ECMO.
PMID- 29331210
TI - To roll the eyes and snap a bite - function, development and evolution of
craniofacial muscles.
AB - Craniofacial muscles, muscles that move the eyes, control facial expression and
allow food uptake and speech, have long been regarded as a variation on the
general body muscle scheme. However, evidence has accumulated that the function
of head muscles, their developmental anatomy and the underlying regulatory
cascades are distinct. This article reviews the key aspects of craniofacial
muscle and muscle stem cell formation and discusses how this differs from the
trunk programme of myogenesis; we show novel RNAseq data to support this notion.
We also trace the origin of head muscle in the chordate ancestors of vertebrates
and discuss links with smooth-type muscle in the primitive chordate pharynx. We
look out as to how the special properties of head muscle precursor and stem
cells, in particular their competence to contribute to the heart, could be
exploited in regenerative medicine.
PMID- 29331208
TI - WRIST: A WRist Image Segmentation Toolkit for carpal bone delineation from MRI.
AB - Segmentation of the carpal bones from 3D imaging modalities, such as magnetic
resonance imaging (MRI), is commonly performed for in vivo analysis of wrist
morphology, kinematics, and biomechanics. This crucial task is typically carried
out manually and is labor intensive, time consuming, subject to high inter- and
intra-observer variability, and may result in topologically incorrect surfaces.
We present a method, WRist Image Segmentation Toolkit (WRIST), for 3D semi
automated, rapid segmentation of the carpal bones of the wrist from MRI. In our
method, the boundary of the bones were iteratively found using prior known
anatomical constraints and a shape-detection level set. The parameters of the
method were optimized using a training dataset of 48 manually segmented carpal
bones and evaluated on 112 carpal bones which included both healthy participants
without known wrist conditions and participants with thumb basilar osteoarthritis
(OA). Manual segmentation by two expert human observers was considered as a
reference. On the healthy subject dataset we obtained a Dice overlap of 93.0 +/-
3.8, Jaccard Index of 87.3 +/- 6.2, and a Hausdorff distance of 2.7 +/- 3.4 mm,
while on the OA dataset we obtained a Dice overlap of 90.7 +/- 8.6, Jaccard Index
of 83.0 +/- 10.6, and a Hausdorff distance of 4.0 +/- 4.4 mm. The short
computational time of 20.8 s per bone (or 5.1 s per bone in the parallelized
version) and the high agreement with the expert observers gives WRIST the
potential to be utilized in musculoskeletal research.
PMID- 29331211
TI - Emerging Mechanisms in Alzheimer's Disease and Their Therapeutic Implications.
PMID- 29331212
TI - Prion Protein as a Toxic Acceptor of Amyloid-beta Oligomers.
AB - The initial report that cellular prion protein (PrPC) mediates toxicity of
amyloid-beta species linked to Alzheimer's disease was initially treated with
scepticism, but growing evidence supports this claim. That there is a high
affinity interaction is now clear, and its molecular basis is being unraveled,
while recent studies have identified possible downstream toxic mechanisms.
Determination of the clinical significance of such interactions between PrPC and
disease-associated amyloid-beta species will require experimental medicine
studies in humans. Trials of compounds that inhibit PrP-dependent amyloid-beta
toxicity are commencing in humans, and although it is clear that only a fraction
of Alzheimer's disease toxicity could be governed by PrPC, a partial, but still
therapeutically useful, role in human disease may soon be testable.
PMID- 29331213
TI - [Methodology for the development of policy brief in public health].
AB - A policy brief is a document that summarizes research to inform policy. In a
brief and succinct way, it defines a policy problem, presents a synthesis of
relevant evidence, identifies possible courses of action and makes
recommendations or key points. The objective of this note is to describe the
methodology used to produce a policy brief for communicating public health
research. This note is based on the model presented by Eugene Bardach in addition
to the authors' own experiences. We describe six steps: 1) identifying the
audience; 2) defining the problem; 3) gathering information and evidence; 4)
consideration of policy alternatives; 5) projecting results and designing
recommendations; and 6) telling the story. We make a case for the use of policy
briefs as a part of an overall communications strategy for research that aims to
bring together research teams and stakeholders.
PMID- 29331214
TI - The Stockholm-3 Model for Prostate Cancer Detection: Algorithm Update, Biomarker
Contribution, and Reflex Test Potential.
AB - BACKGROUND: It has been shown that the Stockholm-3 model (S3M) outperforms
prostate-specific antigen (PSA) as a screening tool for prostate cancer.
OBJECTIVE: To update the S3M, to give a detailed account of the value of each
predictor in the S3M, and to evaluate the S3M as a reflex test for men with PSA
>=3ng/ml. DESIGN, SETTING, AND PARTICIPANTS: During 2012-2015, the Stockholm-3
study evaluated the S3M relative to PSA as tests for Gleason score >=7 prostate
cancers among men aged 50-69 yr. The participants (n=59 159) underwent both
tests, and biopsy was recommended if at least one was positive. A total of 5073
men had a biopsy because of elevated PSA (>=3ng/ml). OUTCOME MEASUREMENTS AND
STATISTICAL ANALYSIS: Logistic regression was used to update the S3M: intact PSA
was removed, HOXB13 was included, and the model was fitted to data from the
Stockholm-3 training and validation cohorts. To compare S3M with PSA, we fixed
the sensitivity for detection of high-grade cancer and evaluated the performance
as the number of biopsies needed to achieve that sensitivity for each test.
RESULTS AND LIMITATIONS: The updated S3M slightly improved the area under the
receiver operating characteristic curve compared to previously published results
(0.75 vs 0.74). When used as a reflex test for men with PSA >=3ng/ml, S3M reduced
the number of biopsies needed by 34% compared to the use of PSA alone, with equal
sensitivity. A limitation is the ethnically homogeneous population. CONCLUSIONS:
A major problem with PSA screening-too many unnecessary biopsies-can be mitigated
if S3M is used as a reflex test. PATIENT SUMMARY: To find aggressive prostate
cancer with the minimum number of negative biopsies and detection of clinically
insignificant cancers, we evaluated the use of a personalized diagnostic
prediction model as a second test for men with a positive prostate-specific
antigen (PSA) test. We found that this two-step approach could reduce prostate
biopsies by a third compared to using PSA alone.
PMID- 29331215
TI - Re: Zhangqun Ye, Guohua Zeng, Huan Yang, et al. Efficacy and Safety of Tamsulosin
in Medical Expulsive Therapy for Distal Ureteral Stones with Renal Colic: A
Multicenter, Randomized, Double-blind, Placebo-controlled Trial. Eur Urol
2018;73:385-91.
PMID- 29331216
TI - Chemoimmunotherapy in Metastatic Urothelial Carcinoma.
PMID- 29331217
TI - The cost of perioperative complications following pancreaticoduodenectomy: A
systematic review.
AB - BACKGROUND/OBJECTIVES: Pancreaticoduodenectomy (PD), also known as a Whipple
procedure, is commonly performed for a variety of benign and malignant tumours,
including of the pancreatic head and surrounding structures. PD is associated
with low mortality but high morbidity and costs. Our objective was to describe
the financial burden of complications following pancreaticoduodenectomy. METHODS:
We searched for articles using the MEDLINE, EMBASE, Cochrane and EconLit
databases from the year 2000. Additional studies were identified by searching
bibliographies. We included studies reporting on hospital cost or charge of in
hospital complications during the index PD admission. Studies including other
surgeries but specifically reporting inpatient complication costs of PD were also
included. Any type of PD was included. Data was collected using a data extraction
table and a narrative synthesis was performed. RESULTS: We identified 15 eligible
articles. All included articles were retrospective studies. Acceptable evidence
for increased cost due to the presence and grade of complication was found.
Strong evidence demonstrated the high rate of complications. Weak evidence linked
complications with specific constituents of hospital cost. Complication grade was
robustly linked with increased length of stay. Not enough evidence was found to
demonstrate a link between PD complications and mortality or readmissions.
LIMITATIONS: Included studies were heterogeneous in setting, methodology, costing
data, and grading systems. CONCLUSIONS: The presence and grade of PD
complications increase hospital cost across diverse settings. The costing
methodology should be transparent and complication grading systems should be
consistent in future studies. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO
2017:CRD42017058427.
PMID- 29331218
TI - Knowing when to stop: Aberrant precision and evidence accumulation in
schizophrenia.
AB - Predictive coding and active inference formulations of the dysconnection
hypothesis suggest that subjects with schizophrenia (SZ) hold unduly precise
prior beliefs to compensate for a failure of sensory attenuation. This implies
that SZ subjects should both initiate responses prematurely during evidence
accumulation tasks and fail to inhibit their responses at long stop-signal
delays. SZ and healthy control subjects were asked to report the timing of
billiards-ball collisions and were occasionally required to withhold their
responses. SZ subjects showed larger temporal estimation errors, which were
associated with premature responses and decreased response inhibition. To account
for these effects, we used hierarchical (Bayesian) drift-diffusion models (HDDM)
and model selection procedures to adjudicate among four hypotheses. HDDM revealed
that the precision of prior beliefs (i.e., starting point) rather than increased
sensory precision (i.e., drift rate) drove premature responses and impaired
response inhibition in patients with SZ. From the perspective of active
inference, we suggest that premature predictions in SZ are responses that,
heuristically, are traded off against accuracy to ensure action execution. On the
basis of previous work, we suggest that the right insular cortex might mediate
this trade-off.
PMID- 29331219
TI - Polycyclic aromatic hydrocarbons in soils and lichen from the western Tibetan
Plateau: Concentration profiles, distribution and its influencing factors.
AB - The Tibetan Plateau (TP) is a huge area and rarely affected by human activity,
and is regarded as one of the most remote regions on the earth. Many studies
about the long-range atmospheric transport (LRAT) of semi-volatile organic
compounds (SVOCs) were conducted in southern and central TP. However, there are
very limited studies focused on PAHs in the western TP and the concentrations
profiles, distribution and its controlling factors in this area remains unclear.
Thus, to explore this knowledge gap, 37 surface soil samples and 23 lichen
samples were collected and analyzed for PAHs. The total concentration of 16 US
EPA's priority PAHs (?16PAHs) in western TP ranges 14.4-59.5ng/g and 38.0-133ng/g
dry weight (dw) with a mean value of 30.8 and 84.6ng/g dw in soil and lichen,
respectively, which is lower than the concentrations in most remote areas
worldwide. In the western TP, low molecular weight PAHs (2-3 rings) are dominant
(occupied 77.4% and 87.9% on average in soil and lichen, respectively), implying
a significant contribution of LRAT in this area. The significant linear
correlations (R2 = 0.372-0.627, p < 0.05) between longitude and soil
concentration suggest a strong impact of the westerly wind on the distribution of
PAHs in soil. In addition, the concentration ratio of lichen/soil (L/S) was found
to linearly increase with the increasing log KOA of individual PAH, suggesting
lichen has a strong ability in filtering more lipophilic airborne pollutants in
western TP.
PMID- 29331220
TI - [Impact of chronic illness on hospital nursing workloads].
AB - OBJECTIVES: To evaluate the short-term impact of chronic illness in hospital
units and to establish a method that allows nursing workloads to be adapted
according to the care needs of patients. METHODS: A descriptive study of the
evolution of workloads of nursing staff associated with the care needs of
patients between 1 July 2014 and 30 June 2016, in a county hospital. The care
needs of the patients were assessed daily using an adaptation of the Montesinos
scheme. The estimated times of nursing care and auxiliary nursing required by the
patients, based on their level of dependence for time distribution, were based on
the standards and recommendations of the Ministry of Health, Social Services and
Equality. RESULTS: During the study period, there was a change in the patient
care needs, with no increase in activity, which resulted in an increase in the
nursing staffing needs of 1,396 theoretical hours per year. This increase implies
an increase in the workforce of 5 nurses in the second period. CONCLUSIONS: In
the study period, the needs for direct nursing care increased by 7%, this
increase is not related to the increase in activity, but to the level of
dependency of the patients with chronic diseases. This increase occurred in both
medical and surgical units.
PMID- 29331221
TI - Mechanisms of changes in functional mitral regurgitation by preload alterations.
AB - BACKGROUND: This study aimed to investigate the mechanisms of acute changes in
functional mitral regurgitation (FMR) by preload alterations. METHODS: Twenty-two
consecutive patients with left ventricular ejection fraction <40% and at least
mild FMR underwent transthoracic echocardiography. Passive leg lifting and
sublingual administration of nitroglycerin were performed to alter preload.
Mitral regurgitant volume (MRV) was assessed using the Doppler method. RESULTS:
MRV changed in parallel with preload alterations. MRV correlated better with
tenting height (TH) than with mitral annular area (MAA) at baseline, whereas the
difference in the correlate coefficients was not statistically significant
(R=0.69 and R=0.40, respectively; p=0.19). On the other hand, changes in MRV
between each sequential stage correlated better with those in MAA than with those
in TH (R=0.68 and R=0.44, respectively; p=0.043). Multiple regression analysis
revealed that baseline TH was the independent determinant of baseline MRV
(R=0.69, p=0.0004), whereas changes in MAA with preload alteration were the
independent determinant of the changes in MRV (R=0.68, p<0.0001). Changes in left
atrial (LA) volume were the independent determinant of the changes in MAA
(R=0.30, p=0.0063). CONCLUSIONS: Acute changes in FMR with preload alterations
resulted from the transverse changes in MAA rather than the longitudinal changes
in tethering-tenting of mitral geometry, and mitral annular deformation was
determined by changes in LA volume. Preload reduction might help heart failure
treatment through the reduction in FMR resulting from the decrease in LA and
mitral annular size.
PMID- 29331222
TI - On-tubing fluorescence measurements of the band broadening of contemporary
injectors in ultra-high performance liquid chromatography.
AB - We report on a detailed study of the injection contribution to band broadening in
contemporary UHPLC-instruments, using either flow-through needle or fixed loop
injection (full loop). Using on-tubing fluorescence measurements at the outlet of
the injector valve, very localized and undisturbed measurements were obtained.
Varying both the flow rate and the injected volume allowed to split the injection
variance (sigmaV2,inj) in a volumetric component (related to the amount injected)
and a hydrodynamic component (related to the flow rate). For the flow-through
needle injector and for the small injection volumes (<2 MUL) typically used in
UHPLC, it was found that the volumetric contribution (i.e. the part of
sigmaV2,inj, that increases with increasing injection volume) is given by a value
of sigmaV2,inj,vol = 0.8 to 1.Vinj2 rather than by the value of 0.125 to
0.2.Vinj2 that is normally assumed in literature. For the hydrodynamic
contribution to sigmaV2,inj, (i..e, the part which remains present even for very
small injection volumes), a clear increase in dispersion with flow rate is found,
reaching a plateau around 0.8ml/min of 0.6 MUL2 or 1.2 MUL2 for the 75 MUm and
120 MUm needle seat capillaries respectively. The difference between both shows
the clear advantage of using a low dispersion 75 MUm injection needle seat
capillary. For a loop-type injector operated in a full-loop mode, the increase in
peak variance with the injection volume is much less pronounced, leading to a
total injector variance given by sigmaV2,inj = 0.34 MUL2 + 0.12.Vinj2 over the
entire range of investigated injection volumes of 1.1 MUL up to 4.5 MUL when
using 120 MUm or narrower ID loops. This expression was nearly completely
independent of the flow rate. For larger ID sample loops, a clear increase of
peak variance with flow rate at fixed injection volume was observed (sigmaV2,inj
increases with 20% for a 170 MUm ID loop and with 70% for a 220 MUm ID loop from
0.3 to 1 ml/min).
PMID- 29331223
TI - Structure-based design and application of a nucleotide coenzyme mimetic ligand:
Application to the affinity purification of nucleotide dependent enzymes.
AB - In the present study, a structure-based approach was exploited for the in silico
design of a nucleotide coenzyme mimetic ligand. The enzyme formate dehydrogenase
(FDH) was employed as a model in our study. The biomimetic ligand was designed
and synthesized based on a tryptamine/3-aminopropylphosphonic acid bi-substituted
1,3,5-triazine (Trz) scaffold (Tra-Trz-3APP), which potentially mimics the
interactions of NAD+-FDH complex. Molecular docking studies of the biomimetic
ligand predicted that it can occupy the same binding site as the natural
coenzyme. Molecular modeling and dynamics simulations revealed that the ligand
binds in an energetically more stable pose in the FDH binding site, as it adopts
a more twisty conformation, compared to the natural coenzyme. Study of the
FDH/Tra-Trz-3APP-Sepharose interaction, through adsorption equilibrium studies
and site-directed mutagenesis of selected FDH coenzyme binding residues, provided
additional experimental evidences of the specificity of the interaction. The Tra
Trz-3APP-Sepharose biomimetic adsorbent was further evaluated towards a range of
different dehydrogenases and was exploited for the development of a single-step
purification protocol for FDH. The protocol afforded enzyme with high yield and
purity, suitable for analytical and industrial purposes.
PMID- 29331224
TI - Centrifugal partition chromatography enables selective enrichment of trimeric and
tetrameric proanthocyanidins for biomaterial development.
AB - Proanthocyanidins (PACs) find wide applications for human use including food,
cosmetics, dietary supplements, and pharmaceuticals. The chemical complexity
associated with PACs has triggered the development of various chromatographic
techniques, with countercurrent separation (CCS) gaining in popularity. This
study applied the recently developed DESIGNER (Depletion and Enrichment of Select
Ingredients Generating Normalized Extract Resources) approach for the selective
enrichment of trimeric and tetrameric PACs using centrifugal partition
chromatography (CPC). This CPC method aims at developing PAC based biomaterials,
particularly for their application in restoring and repairing dental hard tissue.
A general separation scheme beginning with the depletion of polymeric PACs,
followed by the removal of monomeric flavan-3-ols and a final enrichment step
produced PAC trimer and tetramer enriched fractions. A successful application of
this separation scheme is demonstrated for four polyphenol rich plant sources:
grape seeds, pine bark, cinnamon bark, and cocoa seeds. Minor modifications to
the generic DESIGNER CCS method were sufficient to accommodate the varying
chemical complexities of the individual source materials. The step-wise
enrichment of PAC trimers and tetramers was monitored using normal phase TLC and
Diol-HPLC-UV analyses. CPC proved to be a reliable tool for the selective
enrichment of medium size oligomeric PACs (OPACs). This method plays a key role
in the development of dental biomaterials considering its reliability and
reproducibility, as well as its scale-up capabilities for possible larger-scale
manufacturing.
PMID- 29331225
TI - Influence of pressure on the retention of resorcinarene-based cavitands.
AB - The thermodynamics of the retention mechanism of resorcinarene-based cavitands in
RPLC as well as the nature of the binding sites have been studied recently. In
the present study, the influence of pressure on the retention of the cyclic
tetramers on alkylsilyl and polar-embedded C8 and C18 stationary phases is
investigated using aqueous methanol mobile phase. The pressure effect for cavity
shaped molecules has been scarcely studied so far. We observed that the retention
factors of the analytes increased with the increase of the average column
pressure (1-400 bar) when using restricting capillary tubes. The calculated molar
volume changes were negative, between -DeltaVm = 5-19 mL/mol on all types of
stationary phases. Comparing the different stationary phases, we found that the
molar volume changes for both the apolar and more polar analytes were twice
larger on the Hypersil BDS (base deactivated silica) than on the XTerra columns
and they were independent of the length of the alkyl chains of the stationary
phases.
PMID- 29331226
TI - A low complexity minimum variance beamformer for ultrasound imaging using
dominant mode rejection.
AB - In recent years, high resolution adaptive minimum variance-based beamformers have
been successfully applied to medical ultrasound imaging to improve its resolution
and contrast, simultaneously. However, these improvements come at the cost of
much more computational complexity in comparison to the non-adaptive delay-and
sum beamformer. The computational overhead mainly results from the L*L covariance
matrix inversion needed for computation of the adaptive weights, the complexity
of which is cubic with the subarray size, O(L3). In medical ultrasound imaging
with focusing on the imaging point, we have a limited number of dominant modes
and there is no need for the full matrix inversion. Based on this idea, we have
investigated the application of the dominant mode rejection (DMR) adaptive
beamformer for medical ultrasound imaging, which uses only some largest dominant
modes to approximate the covariance matrix in dominant subspace. We show, using
simulated and experimental data, that this subspace dimension can be selected as
low as two resulting in significant computational complexity reduction while
still achieving performance comparable to that of the minimum variance
beamformer.
PMID- 29331229
TI - Hominin raw material procurement in the Oldowan-Acheulean transition at Olduvai
Gorge.
AB - The lithic assemblages at the Oldowan-Acheulean transition in Bed II of Olduvai
Gorge, Tanzania, represent a wide variety of raw materials reflecting both the
diversity of volcanic, metamorphic, and sedimentary source materials available in
the Olduvai basin and surroundings and the preferences of the tool-makers. A
geochemical and petrographic systematic analysis of lava-derived archaeological
stone tools, combined with textural and mineralogical characterization of
quartzite, chert, and other metamorphic and sedimentary raw materials from two
Middle and Upper Bed II sites, has enabled us to produce a comprehensive dataset
and characterization of the rocks employed by Olduvai hominins, which is used
here to establish a referential framework for future studies on Early Stone Age
raw material provenancing. The use of rounded blanks for most lava-derived
artifacts demonstrates that hominins were accessing lava in local stream
channels. Most quartzite artifacts appear to derive from angular blocks, likely
acquired at the source (predominantly Naibor Soit hill), though some do appear to
be manufactured from stream-transported quartzite blanks. Raw material
composition of the EF-HR assemblage indicates that Acheulean hominins selected
high-quality lavas for the production of Large Cutting Tools. On the other hand,
the HWK EE lithic assemblage suggests that raw material selectivity was not
entirely based on rock texture, and other factors, such as blank shape and
availability of natural angles suitable for flaking, played a major role in
Oldowan reduction sequences.
PMID- 29331230
TI - Lower limb articular scaling and body mass estimation in Pliocene and Pleistocene
hominins.
AB - Previous attempts to estimate body mass in pre-Holocene hominins have relied on
prediction equations derived from relatively limited extant samples. Here we
derive new equations to predict body mass from femoral head breadth and proximal
tibial plateau breadth based on a large and diverse sample of modern humans
(avoiding the problems associated with using diaphyseal dimensions and/or
cadaveric reference samples). In addition, an adjustment for the relatively small
femoral heads of non-Homo taxa is developed based on observed differences in hip
to knee joint scaling. Body mass is then estimated for 214 terminal Miocene
through Pleistocene hominin specimens. Mean body masses for non-Homo taxa range
between 39 and 49 kg (39-45 kg if sex-specific means are averaged), with no
consistent temporal trend (6-1.85 Ma). Mean body mass increases in early Homo
(2.04-1.77 Ma) to 55-59 kg, and then again dramatically in Homo erectus and later
archaic middle Pleistocene Homo, to about 70 kg. The same average body mass is
maintained in late Pleistocene archaic Homo and early anatomically modern humans
through the early/middle Upper Paleolithic (0.024 Ma), only declining in the late
Upper Paleolithic, with regional variation. Sexual dimorphism in body mass is
greatest in Australopithecus afarensis (log[male/female] = 1.54), declines in
Australopithecus africanus and Paranthropus robustus (log ratio 1.36), and then
again in early Homo and middle and late Pleistocene archaic Homo (log ratio 1.20
1.27), although it remains somewhat elevated above that of living and middle/late
Pleistocene anatomically modern humans (log ratio about 1.15).
PMID- 29331231
TI - Successful catheter ablation of atrioventricular reentrant tachycardia with left
lateral bypass tract in a patient with unroofed coronary sinus atrial septal
defect.
PMID- 29331227
TI - The impact of technology on the changing practice of lung SBRT.
AB - Stereotactic body radiotherapy (SBRT) for lung tumours has been gaining wide
acceptance in lung cancer. Here, we review the technological evolution of SBRT
delivery in lung cancer, from the first treatments using the stereotactic body
frame in the 1990's to modern developments in image guidance and motion
management. Finally, we discuss the impact of current technological approaches on
the requirements for quality assurance as well as future technological
developments.
PMID- 29331232
TI - Incorporating behavioral and sensory context into spectro-temporal models of
auditory encoding.
AB - For several decades, auditory neuroscientists have used spectro-temporal encoding
models to understand how neurons in the auditory system represent sound. Derived
from early applications of systems identification tools to the auditory
periphery, the spectro-temporal receptive field (STRF) and more sophisticated
variants have emerged as an efficient means of characterizing representation
throughout the auditory system. Most of these encoding models describe neurons as
static sensory filters. However, auditory neural coding is not static. Sensory
context, reflecting the acoustic environment, and behavioral context, reflecting
the internal state of the listener, can both influence sound-evoked activity,
particularly in central auditory areas. This review explores recent efforts to
integrate context into spectro-temporal encoding models. It begins with a brief
tutorial on the basics of estimating and interpreting STRFs. Then it describes
three recent studies that have characterized contextual effects on STRFs,
emerging over a range of timescales, from many minutes to tens of milliseconds.
An important theme of this work is not simply that context influences auditory
coding, but also that contextual effects span a large continuum of internal
states. The added complexity of these context-dependent models introduces new
experimental and theoretical challenges that must be addressed in order to be
used effectively. Several new methodological advances promise to address these
limitations and allow the development of more comprehensive context-dependent
models in the future.
PMID- 29331233
TI - A biophysical modelling platform of the cochlear nucleus and other auditory
circuits: From channels to networks.
AB - Models of the auditory brainstem have been an invaluable tool for testing
hypotheses about auditory information processing and for highlighting the most
important gaps in the experimental literature. Due to the complexity of the
auditory brainstem, and indeed most brain circuits, the dynamic behavior of the
system may be difficult to predict without a detailed, biologically realistic
computational model. Despite the sensitivity of models to their exact
construction and parameters, most prior models of the cochlear nucleus have
incorporated only a small subset of the known biological properties. This
confounds the interpretation of modelling results and also limits the potential
future uses of these models, which require a large effort to develop. To address
these issues, we have developed a general purpose, biophysically detailed model
of the cochlear nucleus for use both in testing hypotheses about cochlear nucleus
function and also as an input to models of downstream auditory nuclei. The model
implements conductance-based Hodgkin-Huxley representations of cells using a
Python-based interface to the NEURON simulator. Our model incorporates most of
the quantitatively characterized intrinsic cell properties, synaptic properties,
and connectivity available in the literature, and also aims to reproduce the
known response properties of the canonical cochlear nucleus cell types. Although
we currently lack the empirical data to completely constrain this model, our
intent is for the model to continue to incorporate new experimental results as
they become available.
PMID- 29331235
TI - Antimullerian hormone as a predictor of live birth following assisted
reproduction: an analysis of 85,062 fresh and thawed cycles from the Society for
Assisted Reproductive Technology Clinic Outcome Reporting System database for
2012-2013.
AB - OBJECTIVE: To determine if serum antimullerian hormone (AMH) is associated with
and/or predictive of live birth assisted reproductive technology (ART) outcomes.
DESIGN: Retrospective analysis of Society for Assisted Reproductive Technology
Clinic Outcome Reporting System database from 2012 to 2013. SETTING: Not
applicable. PATIENT(S): A total of 69,336 (81.8%) fresh and 15,458 (18.2%) frozen
embryo transfer (FET) cycles with AMH values. INTERVENTION(S): None. MAIN OUTCOME
MEASURE(S): Live birth. RESULT(S): A total of 85,062 out of 259,499 (32.7%) fresh
and frozen-thawed autologous non-preimplantation genetic diagnosis cycles had AMH
reported for cycles over this 2-year period. Of those, 70,565 cycles which had
embryo transfers were included in the analysis. Serum AMH was significantly
associated with live birth outcome per transfer in both fresh and FET cycles.
Multiple logistic regression demonstrated that AMH is an independent predictor of
live birth in fresh transfer cycles and FET cycles when controlling for age, body
mass index, race, day of transfer, and number of embryos transferred. Receiver
operating characteristic (ROC) curves demonstrated that the areas under the curve
(AUC) for AMH as predictors of live birth in fresh cycles and thawed cycles were
0.631 and 0.540, respectively, suggesting that AMH alone is a weak independent
predictor of live birth after ART. Similar ROC curves were obtained also when
elective single-embryo transfer (eSET) cycles were analyzed separately in either
fresh (AUC 0.655) or FET (AUC 0.533) cycles, although AMH was not found to be an
independent predictor in eSET cycles. CONCLUSION(S): AMH is a poor independent
predictor of live birth outcome in either fresh or frozen embryo transfer for
both eSET and non-SET transfers.
PMID- 29331234
TI - Metabolic syndrome, hypertension, and hyperlipidemia in mothers, fathers,
sisters, and brothers of women with polycystic ovary syndrome: a systematic
review and meta-analysis.
AB - OBJECTIVE: To provide an evidence-based assessment of metabolic syndrome,
hypertension, and hyperlipidemia in first-degree relatives of women with
polycystic ovary syndrome (PCOS). DESIGN: Systematic review and meta-analysis.
SETTING: Not applicable. PATIENT(S): Mothers, fathers, sisters, and brothers of
women with and without PCOS. INTERVENTION(S): An electronic-based search with the
use of PubMed from 1960 to June 2015 and cross-checked references of relevant
articles. MAIN OUTCOME MEASURE(S): Metabolic syndrome, hypertension and
dyslipidemia, and surrogate markers, including systolic blood pressure (BP),
diastolic BP, total cholesterol, low-density lipoprotein cholesterol, high
density lipoprotein cholesterol, and triglycerides. RESULT(S): Fourteen of 3,346
studies were included in the meta-analysis. Prevalence of the following was
significantly increased in relatives of women with PCOS: metabolic syndrome (risk
ratio [RR] 1.78 [95% confidence interval 1.37, 2.30] in mothers, 1.43 [1.12,
1.81] in fathers, and 1.50 [1.12, 2.00] in sisters), hypertension (RR 1.93 [1.58,
2.35] in fathers, 2.92 [1.92, 4.45] in sisters), and dyslipidemia (RR 3.86 [2.54,
5.85] in brothers and 1.29 [1.11, 1.50] in fathers). Moreover, systolic BP
(mothers, sisters, and brothers), total cholesterol (mothers and sisters), low
density lipoprotein cholesterol (sisters), and triglycerides (mothers and
sisters) were significantly higher in first-degree relatives of PCOS probands
than in controls. CONCLUSION(S): Our results show evidence of clustering for
metabolic syndrome, hypertension, and dyslipidemia in mothers, fathers, sisters,
and brothers of women with PCOS. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO
2016 CRD42016048557.
PMID- 29331236
TI - Pregnancy-related complications and perinatal outcomes resulting from transfer of
cryopreserved versus fresh embryos in vitro fertilization: a meta-analysis.
AB - OBJECTIVE: To provide an updated comparison of pregnancy-related complications
and adverse perinatal outcomes of pregnancies conceived after frozen embryo
transfer (FET) versus fresh embryo transfer (fresh ET). DESIGN: Meta-analysis.
SETTING: University. PATIENT(S): Pregnancies resulting from FET versus fresh ET.
INTERVENTIONS(S): Pubmed, Embase, Cochrane Library, Google Scholar, and Chinese
databases, including the China National Knowledge Infrastructure Database,
Wanfang, and Chinese Scientific Journals Full-Text Database were searched by two
independent reviewers from January 1980 to September 2017. The results were
expressed as risk ratios with 95% confidence intervals. MAIN OUTCOME MEASURE(S):
Pregnancy-related complications and perinatal outcomes. RESULT(S): Our search
retrieved 1,397 articles, of which 31 studies were included. Pregnancies
resulting from FET were associated with lower relative risks of placenta previa,
placental abruption, low birth weight, very low birth weight, very preterm birth,
small for gestational age, and perinatal mortality compared with fresh ET.
Pregnancies occurring from FET were associated with increased risks of pregnancy
induced hypertension, postpartum hemorrhage, and large for gestational age
compared with fresh ET. The risks of gestational diabetes mellitus, preterm
premature rupture of the membranes, and preterm birth (PTB) showed no differences
between the two groups. CONCLUSION(S): Our analysis demonstrated that FET results
in lower risks of placenta previa, placental abruption, low birth weight, very
low birth weight, very preterm birth, small for gestational age, and perinatal
mortality than fresh ET, some differences that are attributed to the increased
risks of pregnancy-induced hypertension, large for gestational age, and
postpartum hemorrhage. Although cryotechnology keeps improving, for comprehensive
consideration, individual approaches remain appropriate to balance the options of
FET or fresh ET at present.
PMID- 29331237
TI - Time-lapse algorithms and morphological selection of day-5 embryos for transfer:
a preclinical validation study.
AB - OBJECTIVE: To determine the agreement between published time-lapse algorithms in
selecting the best day-5 embryo for transfer, as well as the agreement between
these algorithms and embryologists. DESIGN: Prospective study. SETTING: Private
in vitro fertilization center. PATIENT(S): Four hundred and twenty-eight embryos
from 100 cycles cultured in the EmbryoScope. INTERVENTION(S): None. MAIN OUTCOME
MEASURE(S): Interalgorithm agreement as assessed by the Fleiss kappa coefficient.
RESULT(S): Of seven published algorithms analyzed in this study, only one of the
18 possible pairs showed very good agreement (kappa = 0.867); one pair showed
good agreement (kappa = 0.725), four pairs showed fair agreement (kappa = 0.226
0.334), and the remaining 12 pairs showed poor agreement (kappa = 0.008-0.149).
Even in the best-case scenario, the majority of algorithms showed poor to
moderate kappa scores (kappa = 0.337-0.722) for the assessment of agreement
between the embryo(s) selected as "best" by the algorithms and the embryo that
was chosen by the majority (>5) of embryologists, as well as with the embryo that
was actually selected in the laboratory on the day of transfer (kappa = 0.315
0.802). CONCLUSION(S): The results of this study raise concerns as to whether the
tested algorithms are applicable in different clinical settings, emphasizing the
need for proper external validation before clinical use.
PMID- 29331238
TI - In vitro fertilization twins: acceptable when desired, or iatrogenic complication
preventable through elective single embryo transfer?
PMID- 29331239
TI - Sperm donor anonymity: a concept rendered obsolete by modern technology.
PMID- 29331240
TI - A new predictive parameter for embryo transfer success: a path forward is needed
to implement it in technique training.
PMID- 29331241
TI - Evaluation of MALDI-TOF mass spectrometry for the identification of bacteria
growing as biofilms.
AB - We evaluated MALDI-TOF mass spectrometry to identify bacteria from biofilms. We
compared three sample preparation procedures on biofilms grown in vitro. The
extended direct transfer method was able to identify 13 isolates out of 18 (72%)
at the species level and 15 out of 18 (83%) at the genus level.
PMID- 29331242
TI - Species-specific response to sulfide intrusion in native and exotic Mediterranean
seagrasses under stress.
AB - We explored the sulfur dynamics and the relationships between sediment sulfur and
nutrient pools, seagrass structural and physiological variables and sulfide
intrusion in native (Posidonia oceanica, Cymodocea nodosa) and exotic (Halophila
stipulacea) Mediterranean seagrasses at six sites affected by cumulative
anthropogenic pressures to understand the factors controlling sulfide intrusion
in seagrass. Sensitive indicators of seagrass stress (leaf TN, delta15N, TS,
Fsulfide) were increased at several sites, implying that seagrasses are under
pressure. Sulfide intrusion was not related to sediment TOC but it was negatively
related to shoot size and below-ground biomass. Sulfide intrusion in seagrass
tissue was high in P. oceanica (12-17%) and considerably higher in C. nodosa (27
35%). Intrusion was particularly high in H. stipulacea (30-50%), suggesting that
its possible biogeographical expansion due to warming of the Mediterranean may
result in accumulation of sulfides in the sediments and hypoxia/anoxia with
further implications in ecosystem function.
PMID- 29331243
TI - Tolerance and potential for adaptation of a Baltic Sea rockweed under predicted
climate change conditions.
AB - Climate change is threating species' persistence worldwide. To predict species
responses to climate change we need information not just on their environmental
tolerance but also on its adaptive potential. We tested how the foundation
species of rocky littoral habitats, Fucus vesiculosus, responds to combined
hyposalinity and warming projected to the Baltic Sea by 2070-2099. We quantified
responses of replicated populations originating from the entrance, central, and
marginal Baltic regions. Using replicated individuals, we tested for the presence
of within-population tolerance variation. Future conditions hampered growth and
survival of the central and marginal populations whereas the entrance populations
fared well. Further, both the among- and within-population variation in responses
to climate change indicated existence of genetic variation in tolerance. Such
standing genetic variation provides the raw material necessary for adaptation to
a changing environment, which may eventually ensure the persistence of the
species in the inner Baltic Sea.
PMID- 29331244
TI - Perception of faunal circadian rhythms depends on sampling technique.
AB - Ecologists aim at disentangling how species vary in abundance through spatial and
temporal scales, using a range of sampling techniques. Here, we investigated the
circadian rhythm of seagrass-associated decapod crustaceans through three
sampling techniques. Specifically, we compared the abundance, biomass and
structure of seagrass-associated decapod assemblages between the day and night
using a hand net, an airlift pump and baited traps. At night, the hand-net
consistently collected a larger total abundance and biomass of decapods, what
resulted in significant diel differences, which were detected for the total
biomass, but not for the total abundance, when decapods were sampled through an
airlift pump. Traps, however, collected a larger total abundance, but not total
biomass, of decapods during the night. In summary, our perception of faunal diel
rhythms is notably influence by the way organisms are sampled.
PMID- 29331245
TI - Outsmart HPV: Acceptability and short-term effects of a web-based HPV vaccination
intervention for young adult gay and bisexual men.
AB - BACKGROUND: Effective interventions to promote human papillomavirus (HPV)
vaccination are needed, particularly among populations at increased risk of HPV
related disease. We developed and pilot tested a web-based intervention, Outsmart
HPV, to promote HPV vaccination among young gay and bisexual men (YGBM). METHODS:
In 2016, we recruited a national sample (n = 150) of YGBM ages 18-25 in the
United States who had not received any doses of HPV vaccine. Participants were
randomized to receive either standard HPV vaccination information (control) or
population-targeted, individually-tailored content (Outsmart HPV intervention).
We assessed between group differences in HPV vaccination attitudes and beliefs
immediately following the intervention using multiple linear regression. RESULTS:
There were no differences in HPV vaccination attitudes, beliefs and intentions
between groups at baseline. Compared to participants in the control group,
intervention participants reported: greater perception that men who have sex with
men are at higher risk for anal cancer relative to other men (b = 0.34); greater
HPV vaccination self-efficacy (b = 0.15); and fewer perceived harms of HPV
vaccine (b = -0.34) on posttest surveys (all p < .05). Overall, intervention
participants reported high levels of acceptability and satisfaction with the
Outsmart HPV intervention (all > 4.4 on a 5-point scale). CONCLUSIONS: Findings
from this study provide preliminary support for a brief, tailored web-based
intervention in improving HPV vaccination attitudes and beliefs among YGBM. An
important next step is to determine the effects of Outsmart HPV on HPV vaccine
uptake. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT02835755.
PMID- 29331246
TI - Estimation of expected dengue seroprevalence from passive epidemiological
surveillance systems in selected areas of Argentina: A proxy to evaluate the
applicability of dengue vaccination.
AB - BACKGROUND: Current recommendations about dengue vaccination by the World Health
Organization depend on seroprevalence levels and serological status in
populations and individuals. However, seroprevalence estimation may be difficult
due to a diversity of factors. Thus, estimation through models using data from
epidemiological surveillance systems could be an alternative procedure to achieve
this goal. OBJECTIVE: To estimate the expected dengue seroprevalence in children
of selected areas in Argentina, using a simple model based on data from passive
epidemiological surveillance systems. METHODS: A Markov model using a simulated
cohort of individuals from age 0 to 9 years was developed. Parameters regarding
the reported annual incidence of dengue, proportion of inapparent cases, and
expansion factors for outpatient and hospitalized cases were considered as
transition probabilities. The proportion of immune population at 9 years of age
was taken as a proxy of the expected seroprevalence, considering this age as
targeted for vaccination. The model was used to evaluate the expected
seroprevalence in Misiones and Salta provinces and in Buenos Aires city, three
settings showing different climatic favorability for dengue. RESULTS: The
estimates of the seroprevalence for the group of 9-year-old children for Misiones
was 79% (95%CI:46-100%), and for Salta 22% (95%CI:14-30%), both located in
northeastern and northwestern Argentina, respectively. Buenos Aires city, from
central Argentina, showed a likely seroprevalence of 7% (95%CI: 3-11%). According
to the deterministic sensitivity analyses, the parameter showing the highest
influence on these results was the probability of inapparent cases. CONCLUSIONS:
This model allowed the estimation of dengue seroprevalence in settings where this
information is not available. Particularly for Misiones, the expected
seroprevalence was higher than 70% in a wide range of scenarios, thus in this
province a vaccination strategy directed to seropositive children of >9 years
should be analyzed, including further considerations as safety, cost
effectiveness, and budget impact.
PMID- 29331247
TI - A biopsy of Breast Cancer mobile applications: state of the practice review.
AB - BACKGROUND: Breast cancer is the most common cancer in women. The use of mobile
software applications for health and wellbeing promotion has grown exponentially
in recent years. We systematically reviewed the breast cancer apps available in
today's leading smartphone application stores and characterized them based on
their features, evidence base and target audiences. METHODS: A cross-sectional
study was performed to characterize breast cancer apps from the two major
smartphone app stores (iOS and Android). Apps that matched the keywords "breast
cancer" were identified and data was extracted using a structured form. Reviewers
independently evaluated the eligibility and independently classified the apps.
RESULTS: A total of 1473 apps were a match. After removing duplicates and
applying the selection criteria only 599 apps remained. Inter-rater reliability
was determined using Fleiss-Cohen's Kappa. The majority of apps were free 471
(78.63%). The most common type of application was Disease and Treatment
information apps (29.22%), Disease Management (19.03%) and Awareness Raising apps
(15.03%). Close to 1 out of 10 apps dealt with alternative or homeopathic
medicine. The majority of the apps were intended for patients (75.79%). Only one
quarter of all apps (24.54%) had a disclaimer about usage and less than one fifth
(19.70%) mentioned references or source material. Gamification specialists
determined that 19.36% contained gamification elements. CONCLUSIONS: This study
analyzed a large number of breast cancer-focused apps available to consumers.
There has been a steady increase of breast cancer apps over the years. The breast
cancer app ecosystem largely consists of start-ups and entrepreneurs. Evidence
base seems to be lacking in these apps and it would seem essential that expert
medical personnel be involved in the creation of medical apps.
PMID- 29331249
TI - Digital health: A science at crossroads.
PMID- 29331248
TI - Usability evaluation of a commercial inpatient portal.
AB - OBJECTIVES: Patient portals designed for inpatients have potential to increase
patient engagement. However, little is known about how patients use inpatient
portals. To address this gap, we aimed to understand how users 1) interact with,
2) learn to use, and 3) communicate with their providers through an inpatient
portal. MATERIALS AND METHODS: We conducted a usability evaluation using think
aloud protocol to study user interactions with a commercially available inpatient
portal - MyChart Bedside (MCB). Study participants (n=19) were given a tablet
that had MCB installed. They explored MCB and completed eight assigned tasks.
Each session's recordings were coded and analyzed. We analyzed task completion,
errors, and user feedback. We categorized errors into operational errors, system
errors, and tablet-related errors, and indicated their violations of Nielsen's
ten heuristic principles. RESULTS: Participants frequently made operational
errors with most in navigation and assuming non-existent functionalities. We also
noted that participants' learning styles varied, with age as a potential factor
that influenced how they learned MCB. Also, participants preferred to
individually message providers and wanted feedback on status. CONCLUSION: The
design of inpatient portals can greatly impact how patients navigate and
comprehend information in inpatient portals; poor design can result in a
frustrating user experience. For inpatient portals to be effective in promoting
patient engagement, it remains critical for technology developers and hospital
administrators to understand how users interact with this technology and the
resources that may be necessary to support its use.
PMID- 29331250
TI - Inferred joint multigram models for medical term normalization according to ICD.
AB - BACKGROUND: Electronic Health Records (EHRs) are written using spontaneous
natural language. Often, terms do not match standard terminology like the one
available through the International Classification of Diseases (ICD). OBJECTIVE:
Information retrieval and exchange can be improved using standard terminology.
Our aim is to render diagnostic terms written in spontaneous language in EHRs
into the standard framework provided by the ICD. METHODS: We tackle diagnostic
term normalization employing Weighted Finite-State Transducers (WFSTs). These
machines learn how to translate sequences, in the case of our concern,
spontaneous representations into standard representations given a set of samples.
They are highly flexible and easily adaptable to terminological singularities of
each different hospital and practitioner. Besides, we implemented a similarity
metric to enhance spontaneous-standard term matching. RESULTS: From the 2850
spontaneous DTs randomly selected we found that only 7.71% were written in their
standard form matching the ICD. This WFST-based system enabled matching
spontaneous ICDs with a Mean Reciprocal Rank of 0.68, which means that, on
average, the right ICD code is found between the first and second position among
the normalized set of candidates. This guarantees efficient document exchange
and, furthermore, information retrieval. CONCLUSION: Medical term normalization
was achieved with high performance. We found that direct matching of spontaneous
terms using standard lexicons leads to unsatisfactory results while normalized
hypothesis generation by means of WFST helped to overcome the gap between
spontaneous and standard language.
PMID- 29331251
TI - Bridging clinical researcher perceptions and health IT realities: A case study of
stakeholder creep.
AB - PURPOSE: We present a case report detailing a challenge in health information
technology (HIT) project implementations we term "stakeholder creep": not
thoroughly identifying which stakeholders need to be involved and why before
starting a project, consequently not understanding the true effort, skill sets,
social capital, and time required to complete the project. METHODS: A root cause
analysis was performed post-implementation to understand what led to stakeholder
creep. HIT project stakeholders were given a questionnaire to comment on these
misconceptions and a proposed implementation tool to help mitigate stakeholder
creep. FINDINGS: Stakeholder creep contributed to an unexpected increase in time
(3-month delayed go-live) and effort (68% over expected HIT work hours). Four
main clinician/researcher misconceptions were identified that contributed to the
development of stakeholder creep: 1) that EHR IT is a single group; 2) that all
EHR IT members know the entire EHR functionality; 3) that changes to an EHR need
the input of just a single EHR IT member; and 4) that the technological
complexity of a project mirrors the clinical complexity. HIT project stakeholders
similarly perceived clinicians/researchers to hold these misconceptions. The
proposed stakeholder planning tool was perceived to be feasible and helpful.
CONCLUSIONS: Stakeholder creep can negatively affect HIT project implementations.
Projects may be susceptible to stakeholder creep when clinicians/researchers hold
misconceptions related to HIT organization and processes. Implementation tools,
such as the proposed stakeholder checklist, could be helpful in preempting and
mitigating the effect of stakeholder creep.
PMID- 29331252
TI - Investigating the need for clinicians to use tablet computers with a newly
envisioned electronic health record.
AB - OBJECTIVE: The Veterans Health Administration (VHA) has deployed a large number
of tablet computers in the last several years. However, little is known about how
clinicians may use these devices with a newly planned Web-based electronic health
record (EHR), as well as other clinical tools. The objective of this study was to
understand the types of use that can be expected of tablet computers versus
desktops. METHODS: Semi-structured interviews were conducted with 24 clinicians
at a Veterans Health Administration (VHA) Medical Center. RESULTS: An inductive
qualitative analysis resulted in findings organized around recurrent themes of:
(1) Barriers, (2) Facilitators, (3) Current Use, (4) Anticipated Use, (5) Patient
Interaction, and (6) Connection. CONCLUSIONS: Our study generated several
recommendations for the use of tablet computers with new health information
technology tools being developed. Continuous connectivity for the mobile device
is essential to avoid interruptions and clinician frustration. Also, making a
physical keyboard available as an option for the tablet was a clear desire from
the clinicians. Larger tablets (e.g., regular size iPad as compared to an iPad
mini) were preferred. Being able to use secure messaging tools with the tablet
computer was another consistent finding. Finally, more simplicity is needed for
accessing patient data on mobile devices, while balancing the important need for
adequate security.
PMID- 29331253
TI - Evaluation of three machine learning models for self-referral decision support on
low back pain in primary care.
AB - BACKGROUND: Most people experience low back pain (LBP) at least once in their
life and for some patients this evolves into a chronic condition. One way to
prevent acute LBP from transiting into chronic LBP, is to ensure that patients
receive the right interventions at the right moment. We started research in the
design of a clinical decision support system (CDSS) to support patients with LBP
in their self-referral to primary care. For this, we explored the possibilities
of using supervised machine learning. We compared the performances of the three
classification models - i.e. 1. decision tree, 2. random forest, and 3. boosted
tree - to get insight in which model performs best and whether it is already
acceptable to use this model in real practice. METHODS: The three models were
generated by means of supervised machine learning with 70% of a training dataset
(1288 cases with 65% GP, 33% physio, 2% self-care cases). The cases in the
training dataset were fictive cases on low back pain collected during a vignette
study with primary healthcare professionals. We also wanted to know the
performance of the models on real-life low back pain cases that were not used to
train the models. Therefore we also collected real-life cases on low back pain as
test dataset. These cases were collected with the help of patients and healthcare
professionals in primary care. For each model, the performance was measured
during model validation - with 30% of the training dataset -as well as during
model testing - with the test dataset containing real-life cases. The total
observed accuracy as well as the kappa, and the sensitivity, specificity, and
precision were used as performance measures to compare the models. RESULTS: For
the training dataset, the total observed accuracies of the decision tree, the
random forest and boosted tree model were 70%, 69%, and 72% respectively. For the
test dataset, the total observed accuracies were 71%, 53%, and 71% respectively.
The boosted tree appeared to be the best for predicting a referral advice with a
fair accuracy (Kappa between 0.2 and 0.4). Next to this, the measured evaluation
measures show that all models provided a referral advice better than just a
random guess. This means that all models learned some implicit knowledge of the
provided referral advices in the training dataset. CONCLUSIONS: The study showed
promising results on the possibility of using machine learning in the design of
our CDSS. The boosted tree model performed best on the classification of low back
pain cases, but still has to be improved. Therefore, new cases have to be
collected, especially cases that are classified as self-care cases. This to be
sure that also the self-care advice can be predicted well by the model.
PMID- 29331254
TI - Technology alignment in the presence of regulatory changes: The case of
meaningful use of information technology in healthcare.
AB - OBJECTIVES: Using the context of the healthcare sector, this study examines the
impact of regulatory change on technology implementation and use. Hospitals are
now federally mandated to showcase meaningful use of information technology (IT).
We theorize that IT plan scope structured prior to a regulatory change by means
of a long-term planning horizon, top management involvement, and steering
committee engagement impacts organizations' ability to fulfill meaningful use
requirements three to five years later. Furthermore, we contend that this impact
is contingent on the specific IT adoption strategy. METHODS: Data from the HIMSS
and HITECH Act databases were combined to analyze 688 hospitals. Regression
analyses were used to test the hypotheses. RESULTS: The results of this
longitudinal study show that frequency of steering committee meetings and length
of planning horizon broaden IT plan scope. Broader IT plan scope is positively
associated with the ability of organizations to meaningfully use IT. CONCLUSIONS:
The link between IT plan scope and meaningful use metric is particularly
significant for organizations that adopt a more integrated approach towards IT
adoption. Average reimbursement amount differences are provided and discussed
between the different IT adoption strategies.
PMID- 29331255
TI - An automated and robust image processing algorithm for glaucoma diagnosis from
fundus images using novel blood vessel tracking and bend point detection.
AB - Glaucoma is an ocular disease which can cause irreversible blindness. The disease
is currently identified using specialized equipment operated by optometrists
manually. The proposed work aims to provide an efficient imaging solution which
can help in automating the process of Glaucoma diagnosis using computer vision
techniques from digital fundus images. The proposed method segments the optic
disc using a geometrical feature based strategic framework which improves the
detection accuracy and makes the algorithm invariant to illumination and noise.
Corner thresholding and point contour joining based novel methods are proposed to
construct smooth contours of Optic Disc. Based on a clinical approach as used by
ophthalmologist, the proposed algorithm tracks blood vessels inside the disc
region and identifies the points at which first vessel bend from the optic disc
boundary and connects them to obtain the contours of Optic Cup. The proposed
method has been compared with the ground truth marked by the medical experts and
the similarity parameters, used to determine the performance of the proposed
method, have yield a high similarity of segmentation. The proposed method has
achieved a macro-averaged f-score of 0.9485 and accuracy of 97.01% in correctly
classifying fundus images. The proposed method is clinically significant and can
be used for Glaucoma screening over a large population which will work in a real
time.
PMID- 29331256
TI - Measuring non-administration of ordered medications in the pediatric inpatient
setting.
AB - OBJECTIVE: Medication compliance in inpatient settings shows some significant
gaps for adult patients. In pediatric settings prescribing and other
administration errors have been studied but missed doses have not been
specifically studied in the pediatric inpatient setting. We intended to apply
health information technology and data processing methods to study the medication
compliance for pediatric patients at our institution. STUDY DESIGN: We collected
medication ordering, dispensing, and administration data spanning 42 months
(7/1/2010 through 12/31/2013) for pediatric inpatients admitted to a major
tertiary pediatric hospital. We analyzed the orders for which either the
corresponding administration record was missing or the records indicated non
administration. RESULTS: There were only 596 medication orders without
corresponding administration records, accounting for less than 0.05% of 1.6
Million orders for 56,000 patients. There were 40,999 orders with corresponding
administration records indicating non-administration (or less than 3% of all
orders). Overall order compliance of the nursing staff was 97.35%, with another
2.6% of orders having a documented reason for non-administration The top two
medication classes comprising the missed and non-administered orders were
"Alimentary tract and metabolism drugs" and "Nervous system drugs". CONCLUSION:
Measurement of medication compliance is an important quality measure of patient
safety and quality of care. Our study found a small proportion of non
administered medication orders and discovered corresponding reasons illustrating
how health information technology can help to measure the quality of the
medication process from ordering and dispensing to administration at a major
healthcare institution.
PMID- 29331257
TI - Service provision, pricing, and patient satisfaction in online health
communities.
AB - : Background The emergence of online health communities (OHCs) broadens and
diversifies channels for patient-doctor interaction. In recent times, patient
satisfaction has gained new attention within the context of OHCs where unique
patterns are provided: a variety of services with unique attributes are available
in OHCs for patients and doctors have the options of providing and pricing for
different services. OHCs are given high hopes on improving medical efficiency and
patient satisfaction. Knowing how these patterns in OHCs affect patient
satisfaction is crucial for the development of OHCs and medical practices.
METHODS: An empirical research is conducted to examine the effects of provision
and pricing of online services on patient satisfaction by analyzing data from
2309 doctors in a Chinese OHC. RESULTS: The results from this study provided
empirical support, suggesting that service quantity positively influenced patient
satisfaction. A non-linear correlation between service price and satisfaction was
explored and results suggested an inverted U-shaped relationship. At the low
price level, service price led to an increase in patient satisfaction, whereas
the high price level (over 330 CNY/US$49) could have just the opposite effect.
Importantly, we found that price difference between a doctor's different services
significantly decreased patient satisfaction. A mediating effect was tested in
post-hoc analyses, and results revealed that the impact of price difference on
patient satisfaction was partially mediated by flexibility of service selection,
and the mediating effect accounted for 28.6% of the total effect. CONCLUSIONS:
Our results indicate that patient satisfaction can be improved by effectively
providing and pricing services in OHCs. Specifically, doctors can offer different
type services and charge within a reasonable range.
PMID- 29331258
TI - Clinician user involvement in the real world: Designing an electronic tool to
improve interprofessional communication and collaboration in a hospital setting.
AB - OBJECTIVES: User involvement is vital to the success of health information
technology implementation. However, involving clinician users effectively and
meaningfully in complex healthcare organizations remains challenging. The
objective of this paper is to share our real-world experience of applying a
variety of user involvement methods in the design and implementation of a
clinical communication and collaboration platform aimed at facilitating care of
complex hospitalized patients by an interprofessional team of clinicians.
METHODS: We designed and implemented an electronic clinical communication and
collaboration platform in a large community teaching hospital. The design team
consisted of both technical and healthcare professionals. Agile software
development methodology was used to facilitate rapid iterative design and user
input. We involved clinician users at all stages of the development lifecycle
using a variety of user-centered, user co-design, and participatory design
methods. RESULTS: Thirty-six software releases were delivered over 24 months.
User involvement has resulted in improvement in user interface design,
identification of software defects, creation of new modules that facilitated
workflow, and identification of necessary changes to the scope of the project
early on. CONCLUSION: A variety of user involvement methods were complementary
and benefited the design and implementation of a complex health IT solution.
Combining these methods with agile software development methodology can turn
designs into functioning clinical system to support iterative improvement.
PMID- 29331259
TI - Public and physician's expectations and ethical concerns about electronic health
record: Benefits outweigh risks except for information security.
AB - INTRODUCTION: Electronic Health Record systems (EHRs) offer numerous benefits in
health care but also pose certain risks. As we progress toward the implementation
of EHRs, a more in-depth understanding of attitudes that influence overall levels
of EHR support is required. OBJECTIVES: To record public and physicians'
awareness, expectations for, and ethical concerns about the use of EHRs. METHODS:
A convenience sample was surveyed for both the public and physicians. The
Public's Questionnaire was distributed to the public in a printed and an online
version. The Physicians' Questionnaire was distributed to physicians in an online
version. The questionnaires requested demographic characteristics followed by
close-ended questions enquiring about awareness, perceived impact, perceived
risks, and ethical issues raised by EHR use. RESULTS: In total, 46% of the public
and 91% of physicians were aware of EHRs. Physicians' and public opinions were
comparable concerning the positive impact of EHRs on better, more effective, and
faster decisions on the patients' health, on better coordination between
hospitals/clinics and on quality and reduced cost of health care. However,
physicians were concerned that an EHR system would be a burden for their
finances, for their time concerning training on the system, for their everyday
workload and workflow. The majority of the public generally agreed that they
would worry about the possibility that a non-authorized, third party might gain
access to their personal health information (48.8%), and that they would worry
about future discriminations due to possible disclosure of their health
information (48.8%). Most physicians disagreed that EHRs will disrupt the doctor
patient relationship (58.1%) but they would worry about the safety of their
patients' information (53.1%). Overall, both the public and physicians were in
favor of the implementation of an EHR system, evaluating that possible benefits
are more important than possible risks. The majority of the public believed that
physicians should have full access to an EHR (90.9%), whereas nursing staff,
pharmacists, laboratory staff, and other healthcare professional should have
partial access. CONCLUSIONS: The factors identified in the present study present
actionable insights that may increase awareness about EHRs. The survey
illustrates that both the public and physicians acknowledge the benefits and
support EHRs on the condition that sufficient guarantees are provided about
privacy and security.
PMID- 29331261
TI - Necrotizing Granulomatous Inflammation with Airway Tissue Destruction.
PMID- 29331260
TI - Multifaceted behavior of Meckel's diverticulum in children.
AB - PURPOSE/BACKGROUND: Meckel's diverticulum (MD) is one of the most common
congenital malformations of gastrointestinal tract in children. However, the
nonspecific clinical manifestations of MD often cause a diagnostic as well as
therapeutic challenge to pediatric surgeon. This study aimed to review our
experience in managing this disease while evaluating the management strategies.
METHODS: We retrospectively analyzed the clinical data of all patients diagnosed
with MD admitted to our center between January 2010 and December 2015. Factors
documented including demographic criteria, clinical manifestations, preoperative
examinations, surgical methods, histopathological characteristics, postoperative
complications, and outcomes. RESULTS: The patients included 210 males and 76
females, aged from 1day to 15years. In fifty three patients, the MD was an
incidental finding at laparotomy or laparoscopy. The remaining 233 patients were
symptomatic and presented with various clinical features. Ninety nine patients
presented with episodes of bleeding per rectum or melena. Fifty six patients
demonstrated symptoms of diverticulitis or perforated MD. Forty patients were
diagnosed as intestinal obstruction, and 35 patients with intussusception
requiring surgical reduction. Two cases of Littre hernia and one case of foreign
body trapped in MD were also observed in this group. Six patients misdiagnosed as
appendicitis at another institution were reoperated in our department. Among the
99 patients with bleeding per rectum, 78 underwent a Tc-99m scan that showed a
positive tracer in 55 patients and negative in 23. All patients underwent
resection of the diverticulum, except for 2 cases of postponed resection.
Histology revealed ectopic gastric mucosa or ectopic pancreatic tissue in 154
patients; significant differences were observed between the symptomatic group and
the accidentally found group. One patient died of peritonitis and sepsis
postoperatively; one case of anastomotic leak and one case of adhesive intestinal
obstruction were reoperated. CONCLUSION: Meckel's diverticulum has various
clinical presentations and it is difficult to make a precise diagnosis
preoperatively. It is necessary to maintain a high suspicion of MD in the
pediatric age group with symptoms of abdominal pain, gastrointestinal hemorrhage
or intestinal obstruction. Heterotopic tissue is the main cause of complicated
diverticulum, and it is safe and feasible to remove the incidentally found MD.
Laparoscopy should become the first choice of methods in diagnosis and treatment
of MD. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: Level IV.
PMID- 29331262
TI - Can Interrogation of Tumour Characteristics Lead us to Safely Omit Adjuvant
Radiotherapy in Patients with Early Breast Cancer?
AB - Adjuvant radiotherapy after breast-conserving surgery has been an important
component of the standard of care for early breast cancer. Improvements in breast
cancer care have resulted in a substantial reduction in local relapse rates over
recent decades. Although the proportional benefits of adjuvant radiotherapy are
similar for different prognostic risk groups of patients, the absolute benefits
depend on the risk of relapse and therefore vary considerably between prognostic
groups. Radiotherapy is not without risk and for some patients at very low risk
of relapse the risks of radiotherapy may outweigh the benefit, leading to
potential overtreatment. Randomised controlled trial (RCT) evidence shows that
omission of radiotherapy in low risk early breast cancer does not reduce overall
survival or increase breast cancer mortality and local recurrences are
salvageable. Despite this there has not been a change in practice regarding
omission of radiotherapy. The reasons for this may include challenges in patient
selection. Recent advances in immunohistochemistry and genomic profiling may
improve risk stratification and the development of biomarkers to directed
therapies. Several RCTs have quantified the benefit of radiotherapy in reducing
local relapse. Where a treatment benefit is known but is considered to be so
small not to be clinically relevant then alternatives to RCTs may be considered
to answer the question of need. This is because we can assess risk against a
fixed 'absolute' boundary rather than needing a randomised comparator. The
prospective cohort study is an alternative to the RCT design to answer the
question of need for radiotherapy. The feasibility of recruitment into biomarker
directed de-escalation studies will become apparent as more studies open. The
challenge is to determine if we are able to accurately risk stratify patients and
avoid unnecessary toxicity, thereby tailoring the need for adjuvant breast
radiotherapy on an individual patient basis.
PMID- 29331263
TI - Glial scars are permeable to the neurotoxic environment of chronic stroke
infarcts.
AB - Following stroke, the damaged tissue undergoes liquefactive necrosis, a stage of
infarct resolution that lasts for months although the exact length of time is
currently unknown. One method of repair involves reactive astrocytes and
microglia forming a glial scar to compartmentalize the area of liquefactive
necrosis from the rest of the brain. The formation of the glial scar is a
critical component of the healing response to stroke, as well as other central
nervous system (CNS) injuries. The goal of this study was to evaluate the
toxicity of the extracellular fluid present in areas of liquefactive necrosis and
determine how effectively it is segregated from the remainder of the brain. To
accomplish this goal, we used a mouse model of stroke in conjunction with an
extracellular fluid toxicity assay, fluorescent and electron microscopy,
immunostaining, tracer injections into the infarct, and multiplex immunoassays.
We confirmed that the extracellular fluid present in areas of liquefactive
necrosis following stroke is toxic to primary cortical and hippocampal neurons
for at least 7 weeks following stroke, and discovered that although glial scars
are robust physical and endocytic barriers, they are nevertheless permeable. We
found that molecules present in the area of liquefactive necrosis can leak across
the glial scar and are removed by a combination of paravascular clearance and
microglial endocytosis in the adjacent tissue. Despite these mechanisms, there is
delayed atrophy, cytotoxic edema, and neuron loss in regions adjacent to the
infarct for weeks following stroke. These findings suggest that one mechanism of
neurodegeneration following stroke is the failure of glial scars to impermeably
segregate areas of liquefactive necrosis from surviving brain tissue.
PMID- 29331264
TI - Altered levels of the splicing factor muscleblind modifies cerebral cortical
function in mouse models of myotonic dystrophy.
AB - Myotonic dystrophy (DM) is a progressive, multisystem disorder affecting skeletal
muscle, heart, and central nervous system. In both DM1 and DM2, microsatellite
expansions of CUG and CCUG RNA repeats, respectively, accumulate and disrupt
functions of alternative splicing factors, including muscleblind (MBNL) proteins.
Grey matter loss and white matter changes, including the corpus callosum, likely
underlie cognitive and executive function deficits in DM patients. However,
little is known how cerebral cortical circuitry changes in DM. Here, flavoprotein
optical imaging was used to assess local and contralateral responses to
intracortical motor cortex stimulation in DM-related mouse models. In control
mice, brief train stimulation generated ipsilateral and contralateral homotopic
fluorescence increases, the latter mediated by the corpus callosum. Single pulse
stimulation produced an excitatory response with an inhibitory-like surround
response mediated by GABAA receptors. In a mouse model of DM2 (Mbnl2 KO), we
observed prolonged and increased responsiveness to train stimulation and loss of
the inhibition from single pulse stimulation. Conversely, mice overexpressing
human MBNL1 (MBNL1-OE) exhibited decreased contralateral response to train
stimulation and reduction of inhibitory-like surround to single pulse
stimulation. Therefore, altering levels of two key DM-associated splicing factors
modifies functions of local cortical circuits and contralateral responses
mediated through the corpus callosum.
PMID- 29331266
TI - Human papilloma virus-specific T cells can be generated from naive T cells for
use as an immunotherapeutic strategy for immunocompromised patients.
AB - Human papilloma virus (HPV) is a known cause of cervical cancer, squamous cell
carcinoma and laryngeal cancer. Although treatments exist for HPV-associated
malignancies, patients unresponsive to these therapies have a poor prognosis.
Recent findings from vaccine studies suggest that T-cell immunity is essential
for disease control. Because Epstein-Barr Virus (EBV)-specific T cells have been
highly successful in treating or preventing EBV-associated tumors, we
hypothesized that the development of a manufacturing platform for HPV-specific T
cells from healthy donors could be used in a third-party setting to treat
patients with high-risk/relapsed HPV-associated cancers. Most protocols for
generating virus-specific T cells require prior exposure of the donor to the
targeted virus and, because the seroprevalence of high-risk HPV types varies
greatly by age and ethnicity, manufacturing of donor-derived HPV-specific T cells
has proven challenging. We, therefore, made systematic changes to our current
Good Manufacturing Practice (GMP)-compliant protocols to improve antigen
presentation, priming and expansion for the manufacture of high-efficacy HPV
specific T cells. Like others, we found that current methodologies fail to expand
HPV-specific T cells from most healthy donors. By optimizing dendritic cell
maturation and function with lipopolysaccharide (LPS) and interferon (IFN)gamma,
adding interleukin (IL)-21 during priming and depleting memory T cells, we
achieved reliable expansion of T cells specific for oncoproteins E6 and E7 to
clinically relevant amounts (mean, 578-fold expansion; n = 10), which were
polyfunctional based on cytokine multiplex analysis. In the third-party setting,
such HPV-specific T-cell products might serve as a potent salvage therapy for
patients with HPV-associated diseases.
PMID- 29331265
TI - Mechanisms of Memory Disruption in Depression.
AB - Depressed individuals typically show poor memory for positive events, potentiated
memory for negative events, and impaired recollection. These phenomena are
clinically important but poorly understood. Compelling links between stress and
depression suggest promising candidate mechanisms. Stress can suppress
hippocampal neurogenesis, inhibit dopamine neurons, and sensitize the amygdala.
We argue that these phenomena may impair pattern separation, disrupt the encoding
of positive experiences, and bias retrieval toward negative events, respectively,
thus recapitulating core aspects of memory disruption in depression.
Encouragingly, optogenetic reactivation of cells engaged during the encoding of
positive memories rapidly reduces depressive behavior in preclinical models.
Thus, many memory deficits in depression appear to be downstream consequences of
chronic stress, and addressing memory disruption can have therapeutic value.
PMID- 29331267
TI - Identification and initial optimization of inhibitors of Clostridium difficile
(C. difficile) toxin B (TcdB).
AB - The discovery, synthesis and preliminary structure-activity relationship (SAR) of
a novel class of inhibitors of Clostridium difficile (C. difficile) toxin B
(TcdB) is described. A high throughput screening (HTS) campaign resulted in the
identification of moderately active screening hits 1-5 the most potent of which
was compound 1 (IC50 = 0.77 uM). In silico docking of an early analog offered
suggestions for structural modification which resulted in the design and
synthesis of highly potent analogs 13j(IC50 = 1 nM) and 13 l(IC50 = 7 nM) which
were chosen as leads for further optimization.
PMID- 29331268
TI - The Population Biology and Transmission Dynamics of Loa loa.
AB - Endemic to Central Africa, loiasis - or African eye worm (caused by the filarial
nematode Loa loa) - affects more than 10 million people. Despite causing ocular
and systemic symptoms, it has typically been considered a benign condition, only
of public health relevance because it impedes mass drug administration-based
interventions against onchocerciasis and lymphatic filariasis in co-endemic
areas. Recent research has challenged this conception, demonstrating excess
mortality associated with high levels of infection, implying that loiasis
warrants attention as an intrinsic public health problem. This review summarises
available information on the key parasitological, entomological, and
epidemiological characteristics of the infection and argues for the mobilisation
of resources to control the disease, and the development of a mathematical
transmission model to guide deployment of interventions.
PMID- 29331269
TI - Clinical benefits of autologous haematopoietic stem cell transplantation in type
1 diabetes patients.
AB - : Type 1 diabetes (T1D) is characterized by severe damage to pancreas islet
function through immunological attack; therefore, it is also called 'insulin
dependent diabetes'. The present study aimed to evaluate the safety and clinical
efficacy of autologous haematopoietic stem cell transplantation (AHSCT) in
adolescent patients with newly diagnosed T1D. A phase-II prospective, parallel
assignment, non-randomized trial was conducted from March 2008 to December 2011
with 40 T1D patients, of whom 20 received AHSCT therapy and 20 were treated only
with insulin injections. Of these patients, 14 (70%) in the AHSCT group became
insulin-independent for 1.5 to 48 months compared with only one patient in the
Insulin group. Of these 14 AHSCT patients, 11 relapsed within a median time of
19.5 (range 5.5-1) months and resumed insulin use. By the end of the 4-year
follow-up, the difference in daily insulin dosages between the AHSCT and Insulin
groups had become smaller (0.49+/-0.32IU/kg/day vs. 0.79+/-0.18IU/kg/day,
respectively; P<0.01). C-peptide levels increased significantly at 3 months in
both groups and later decreased, with the insulin group showing more rapid
deterioration. Most of the adverse events in the AHSCT group were transplantation
complications. Our data suggest that AHSCT treatment was well tolerated and
slowed deterioration of islet beta-cell function while significantly decreasing
daily insulin dosages. However, because of the high relapse rate, more
information on longer-term outcomes is needed before AHSCT can be routinely
considered for T1D patients. SIGNIFICANCE: although this was a non-randomized
clinical study, this phase-II trial demonstrated the beneficial effects of AHSCT
in patients with newly diagnosed T1D by increasing C-peptide levels and inducing
insulin independence, while showing its safety and good tolerability compared
with conventional intensive insulin therapy. Thus, these results are helpful for
increasing our understanding of the use of haematopoietic stem cell therapy in
the treatment of T1D and for evaluating whether it can become more widespread in
future.
PMID- 29331271
TI - The durability of operational improvements with rotational patient assignment.
AB - INTRODUCTION: Previous work has suggested that Emergency Department rotational
patient assignment (a system in which patients are algorithmically assigned to
physicians) is associated with immediate (first-year) improvements in operational
metrics. We sought to determine if these improvements persisted over a longer
follow-up period. METHODS: Single-site, retrospective analysis focused on years 2
4 post-implementation (follow-up) of a rotational patient assignment system. We
compared operational data for these years with previously published data from the
last year of physician self-assignment and the first year of rotational patient
assignment. We report data for patient characteristics, departmental
characteristics and facility characteristics, as well as outcomes of length of
stay (LOS), arrival to provider time (APT), and rate of patients who left before
being seen (LBBS). RESULTS: There were 140,673 patient visits during the five
year period; 138,501 (98.7%) were eligible for analysis. LOS, APT, and LBBS
during follow-up remained improved vs. physician self-assignment, with
improvements similar to those noted in the first year of implementation. Compared
with the last year of physician self-assignment, approximate yearly average
improvements during follow-up were a decrease in median LOS of 18min (8%
improvement), a decrease in median APT of 21min (54% improvement), and a decrease
in LBBS of 0.69% (72% improvement). CONCLUSION: In a single facility study,
rotational patient assignment was associated with sustained operational
improvements several years after implementation. These findings provide further
evidence that rotational patient assignment is a viable strategy in front-end
process redesign.
PMID- 29331270
TI - Severe beta blocker and calcium channel blocker overdose: Role of high dose
insulin.
AB - A 54-year-old female presented after taking an overdose of an unknown amount of
hydrochlorothiazide, doxazocin, atenolol and amlodipine. She was initially
refractory to treatment with conventional therapy (intravenous fluids, activated
charcoal, glucagon 5 mg followed with glucagon drip, calcium gluconate 10%, and
atropine). Furthermore, insulin at 4 U/kg was not effective in improving her
hemodynamics. Shortly after high dose insulin was achieved with 10 U/kg, there
was dramatic improvement in hemodynamics resulting in three of five vasopressors
being weaned off in 8 h. She was subsequently off all vasopressors after six
additional hours. The role of high dose insulin has been documented in prior
cases, however it is generally recommended after other conventional therapies
have failed. However, there are other reports that suggest it as initial therapy.
Our patient failed conventional therapies and responded well only with maximum
dose of insulin. Physicians should consider high dose insulin early in severe
beta blocker or calcium channel blocker overdose for improvement in hemodynamics.
This leads to early discontinuation of vasopressors. It is important that
emergency physicians be aware of the beneficial effects of high dose insulin when
initiated early as opposed to waiting for conventional therapy to fail; as these
patients often present first to the emergency department. Early initiation in the
emergency department can be beneficial in these patients.
PMID- 29331272
TI - High-Sensitivity Cardiac Troponin and New-Onset Heart Failure: A Systematic
Review and Meta-Analysis of 67,063 Patients With 4,165 Incident Heart Failure
Events.
AB - OBJECTIVES: The aim of this study was to systematically collate and appraise the
available evidence regarding the association between high-sensitivity cardiac
troponin (hs-cTn) and incident heart failure (HF) and the added value of hs-cTn
in HF prediction. BACKGROUND: Identification of subjects at high risk for HF and
early risk factor modification with medications such as angiotensin-converting
enzyme inhibitors may delay the onset of HF. Hs-cTn has been suggested as a
prognostic marker for the incidence of first-ever HF in asymptomatic subjects.
METHODS: PubMed, Embase, and Web of Science were systematically searched for
prospective cohort studies published before January 2017 that reported
associations between hs-cTn and incident HF in subjects without baseline HF.
Study-specific multivariate-adjusted hazard ratios (HRs) were pooled using random
effects meta-analysis. RESULTS: Data were collated from 16 studies with a total
of 67,063 subjects and 4,165 incident HF events. The average age was 57 years,
and 47% were women. Study quality was high (Newcastle-Ottawa score 8.2 of 9). In
a comparison of participants in the top third with those in the bottom third of
baseline values of hs-cTn, the pooled multivariate-adjusted HR for incident HF
was 2.09 (95% confidence interval [CI]: 1.76 to 2.48; p < 0.001). Between-study
heterogeneity was high, with an I2 value of 80%. HRs were similar in men and
women (2.29 [95% CI: 1.64 to 3.21] vs. 2.18 [95% CI: 1.68 to 2.81]) and for hs
cTnI and hs-cTnT (2.09 [95% CI: 1.53 to 2.85] vs. 2.11 [95% CI: 1.69 to 2.63])
and across other study-level characteristics. Further adjustment for B-type
natriuretic peptide yielded a similar HR of 2.08 (95% CI: 1.64 to 2.65). Assay of
hs-cTn in addition to conventional risk factors provided improvements in the C
index of 1% to 3%. CONCLUSIONS: Available prospective studies indicate a strong
association of hs-cTn with the risk of first-ever HF and significant improvements
in HF prediction.
PMID- 29331273
TI - Meta-Analyses and Interpretation of Troponin Values in Heart Failure.
PMID- 29331274
TI - Clinical outcomes of endoscopic submucosal dissection for large colorectal
laterally spreading tumors in older adults.
AB - BACKGROUND AND AIMS: The colorectal endoscopic submucosal dissection (ESD)
remains technically challenging, especially for older patients who frequently
encounter complex chronic diseases and have a loose colon. However, only limited
number of studies are available for the safety of ESD in older patients with
especially large laterally spreading tumors. Therefore, in this retrospective
study, we compared the outcomes of ESD for laterally spreading tumors (LST)
>=3cm(cm) in older patients to that in younger patients. METHODS: Consecutive
patients with LSTs 3cm or larger were enrolled for from May 2010-2016. These
patients were divided into two groups: the younger group (<65years) and the older
group (>=65years). The clinicopathologic findings and the outcomes of ESD
procedures were compared between the two groups. RESULTS: A total of 70 patients
in the younger group and 73 patients in the older group were treated by ESD for
colorectal LSTs larger than 3cm. No significant differences were observed in the
gender ratio, tumor morphological type, tumor location, and tumor size between
the two groups. The en bloc resection rates were 85.7 and 89.0%, respectively,
without a significant difference. The procedural time was similar between the
younger and older patients (71.8+/-34.7min vs. 70.6+/-29.5min). The duration of
hospital stay was not significantly different between the two groups (4.1+/
2.2days vs. 4.4+/-2.5days). No significant differences were observed between the
two groups with respect to ESD-related complications including delayed bleeding,
perforation, and stricture. CONCLUSIONS: ESD appears to be an effective and safe
method for LSTs larger than 3cm in older patients.
PMID- 29331275
TI - Low-level cadmium exposure and cardiovascular outcomes in elderly Australian
women: A cohort study.
AB - BACKGROUND: Cadmium has been associated with increased risk of cardiovascular
disease (CVD) in observational studies, however there has been a limited focus on
this relationship in women. OBJECTIVES: This study investigated the association
of urinary cadmium (UCd) concentrations with CVD outcomes and all-cause mortality
in elderly Western Australian (WA) women. METHODS: UCd excretion was measured at
baseline in 1359 women, mean age 75.2 +/- 2.7 years and 14.5 years of
atherosclerotic vascular disease (ASVD) hospitalisations and deaths, including
both the principle cause of death and all associated causes of death. Health
outcome data were retrieved from the Western Australian Data Linkage System. Cox
regression analysis was used to estimate hazard ratios of ASVD and all-cause
mortality. UCd was ln-transformed and models were adjusted for demographic and
CVD risk factors. RESULTS: Median (IQR) concentration of UCd was 0.18 (0.09-0.32)
MUg/L. In multivariable-adjusted analyses per ln unit (equivalent to ~2.7 fold)
increase in UCd, there was a 36% increase in the risk of death from heart failure
and 17% increase in the risk of a heart failure event, respectively (HR = 1.36,
95% CI 1.11-1.67; HR = 1.17, 95% CI 1.01-1.35). When analyses were restricted to
never smokers the relationship between UCd and death from heart failure remained
(HR 1.29, 95% CI 1.01-1.63). CONCLUSIONS: This study suggests that even at low
levels of exposure cadmium may be associated with heart failure hospitalisations
and deaths in older women, however given the dilute nature of these urine
samples, the results must be interpreted with caution.
PMID- 29331276
TI - Analyzing recommender systems for health promotion using a multidisciplinary
taxonomy: A scoping review.
AB - BACKGROUND: Recommender systems are information retrieval systems that provide
users with relevant items (e.g., through messages). Despite their extensive use
in the e-commerce and leisure domains, their application in healthcare is still
in its infancy. These systems may be used to create tailored health
interventions, thus reducing the cost of healthcare and fostering a healthier
lifestyle in the population. OBJECTIVE: This paper identifies, categorizes, and
analyzes the existing knowledge in terms of the literature published over the
past 10 years on the use of health recommender systems for patient interventions.
The aim of this study is to understand the scientific evidence generated about
health recommender systems, to identify any gaps in this field to achieve the
United Nations Sustainable Development Goal 3 (SDG3) (namely, "Ensure healthy
lives and promote well-being for all at all ages"), and to suggest possible
reasons for these gaps as well as to propose some solutions. METHODS: We
conducted a scoping review, which consisted of a keyword search of the literature
related to health recommender systems for patients in the following databases:
ScienceDirect, PsycInfo, Association for Computing Machinery, IEEExplore, and
Pubmed. Further, we limited our search to consider only English-language journal
articles published in the last 10 years. The reviewing process comprised three
researchers who filtered the results simultaneously. The quantitative synthesis
was conducted in parallel by two researchers, who classified each paper in terms
of four aspects-the domain, the methodological and procedural aspects, the health
promotion theoretical factors and behavior change theories, and the technical
aspects-using a new multidisciplinary taxonomy. RESULTS: Nineteen papers met the
inclusion criteria and were included in the data analysis, for which thirty-three
features were assessed. The nine features associated with the health promotion
theoretical factors and behavior change theories were not observed in any of the
selected studies, did not use principles of tailoring, and did not assess (cost)
effectiveness. DISCUSSION: Health recommender systems may be further improved by
using relevant behavior change strategies and by implementing essential
characteristics of tailored interventions. In addition, many of the features
required to assess each of the domain aspects, the methodological and procedural
aspects, and technical aspects were not reported in the studies. CONCLUSIONS: The
studies analyzed presented few evidence in support of the positive effects of
using health recommender systems in terms of cost-effectiveness and patient
health outcomes. This is why future studies should ensure that all the proposed
features are covered in our multidisciplinary taxonomy, including integration
with electronic health records and the incorporation of health promotion
theoretical factors and behavior change theories. This will render those studies
more useful for policymakers since they will cover all aspects needed to
determine their impact toward meeting SDG3.
PMID- 29331277
TI - Unplanned reoperation after hepatectomy: an analysis of risk factors and
outcomes.
AB - BACKGROUND/PURPOSE: Reoperation is being increasingly utilized as a metric for
surgical care quality. The aim of this study was to identify the incidence of and
risk factors for unplanned reoperation following index hepatectomy. METHODS: Pre,
intra- and post-operative information of patients who underwent partial
hepatectomy in 435 hospitals participating in the American College of Surgeons
National Surgical Quality Improvement Program from 2011 to 2013 were analyzed.
RESULTS: 343 (4%) of 9195 patients required reoperation within 30 days of index
hepatectomy. The index procedures with the highest incidence of reoperation (%)
were trisectionectomy (7%) and right hepatectomy (5%). Patients who underwent
reoperation had increased index operative duration (323 +/- 174 min versus 243 +/
125 min, p < 0.001), postoperative transfusion (57% versus 23%, p < 0.001),
wound complications, cardiorespiratory, renal, thromboembolic, and infectious
events. Hemorrhage was the most common indication for reoperation (10%). Male
gender, ASA class 4, and right hepatectomy or trisectionectomy were independent
predictors of reoperation (OR 1.4 [1.1-1.7], p = 0.007; 2.0 [1.3-3.1], p = 0.003;
1.6 [1.2-2.0], p = 0.001 and 2.5 [1.8-3.4], p < 0.001, respectively). All
reoperations occurred during index hospitalization and resulted in longer mean
length of stay (19 +/- 17 days versus 7 +/- 7 days, p < 0.001). CONCLUSION:
Reoperation is associated with several patient characteristics and procedural
factors in this national sample. Knowledge of these factors can increase
awareness of patients at risk for reoperation.
PMID- 29331278
TI - Impact of treatment with a Protein Tyrosine Kinase Inhibitor (Genistein) on acute
and chronic experimental Schistosoma mansoni infection.
AB - Schistosomiasis mansoni is considered one of the most common fibrotic diseases
resulting from inflammation and deposition of fibrous tissue around parasitic
eggs trapped in the liver, causing morbidity and mortality. Chemotherapy against
schistosomiasis is largely dependent on Praziquantel (PZQ). Yet, the huge
administration of it in endemic areas and its incompetence towards the immature
stages have raised serious alarms against the development of drug resistance. Few
drugs are directed to reverse schistosomal liver fibrosis, particularly at the
chronic and advanced stages of the disease. Recently, protein tyrosine kinase
(PTK) inhibitors have been identified as potent anti-schistosomal and anti
fibrotic drugs against schistosomes, that may suppress and reverse Schistosoma
mansoni (S. mansoni) induced liver fibrosis. The present study was designed to
assess the anti-schistosomal and antifibrotic activity of Genistein, a PTK
inhibitor, in comparison to PZQ, on both acute and chronic S. mansoni-infected
mice using different parasitological, histopathological and immunohistochemical
studies. Genistein showed a significant reduction (P < .05) in total worm burden,
tissue egg load, mean hepatic granulomas diameter and numbers, percentage of
collagen and expression of transforming growth factor-beta 1 (TGF-beta 1) in the
examined hepatocytes with elevation in percentage of degenerated ova, in
comparison to the control groups, in both acute and chronic stages of infection.
The best results were obtained when Genistein was combined with PZQ. Therefore,
it was concluded that Genistein showed a promising anti-schistosomal and anti
fibrotic properties which could make it one of the new potential targets in
chemotherapy against schistosomiasis.
PMID- 29331279
TI - Dynamics of spatiotemporal distribution of schistosomiasis in Hubei Province,
China.
AB - Schistosomiasis caused by parasitic flatworms of blood flukes, remains a major
public health concern in China. The significant progress in controlling
schistosomiasis in China over the past decades has resulted in the remarkable
reduction in the prevalence and intensity of Schistosoma japonicum infection to
an extremely low level. Therefore, the elimination of schistosomiasis has been
promoted by the Chinese national government. Hubei Province is the major endemic
area, that is, along the middle and low reaches of the Yangtze River in the lake
and marshland regions of southern China. Eliminating the transmission of
schistosomiasis in Hubei Province is challenging. The current issue is to
determine the distributions and clusters of schistosomiasis transmission. In this
study, we assessed the spatial distribution of schistosomiasis and the risk at
the county level in Hubei Province from 2011 to 2015 to provide guidance on the
elimination of schistosomiasis transmission in lake and marshland regions.
Spatial database of human S.japonicum infection from 2011 to 2015 at the county
level in the study area was built based on the annual schistosomias is
surveillance data. Moran's I, the global spatial autocorrelation statistics, was
utilized to describe the spatial autocorrelation of human S. japonicum infection.
In addition, purely spatial scan statistics combined with space-time scan
statistics were used to determine the epidemic clusters. Infection rates of S.
japonicum decreased in each endemic county in Hubei from 2011 to 2015. Human S.
japonicum infection rate showed statistical significance by global
autocorrelation analysis during the study period (Moran's I > 0, P < 0.01). This
result suggested that there were spatial clusters present in the distribution of
S. japonicum infection for the five years. Purely spatial analysis of human S.
japonicum infection showed one most likely cluster and one secondary cluster from
2011 to 2015, which covered four and one counties, respectively. Spatiotemporal
clustering analysis determined one most likely cluster and one secondary cluster
both in 2011-2012, which appeared in 4 and 5 counties, respectively. However, the
number of clustering foci decreased with time, and no cluster was detected after
2013.The clustering foci were both located at the Jianghan Plain, along the
middle reaches of the Yangtze River and its connecting branch Hanbei River.
Spatial distribution of human S. japonicum infections did not change temporally
at the county level in Hubei Province. A declining trend in spatiotemporal
clustering was observed between 2011 and 2015. However, effective control
strategies and integrated prevention should be continuously performed, especially
at the Jianghan Plain area along the Yangtze and Hanbei River Basin. Multivariate
statistical analysis was carried out to investigate the risk of missing
examinations, missing treatment, and unstandardized treatment events. The results
showed that age, education level and Sanitary latrines are risk factors for
missing examinations (b > 0, OR >1), and treatment times in past and feeding
cattle in village group are protective factors (b < 0, OR <1). We also found that
age and education level are risk factors for missing treatment (b > 0, OR >1).
Study of the risk for un-standardized treatment revealed that occupation is risk
factors (b > 0, OR >1), though, education level is protective factors (b < 0, OR
<1). Therefore, precise prevention and control should be mainly targeted at these
special populations.
PMID- 29331280
TI - [Jurisdictions on the reimbursement of new medical technologies by public health
insurance: A systematic review].
AB - BACKGROUND: In Germany reimbursement for new medical technologies is often
enforced before a social court. It is likely that these judicial decisions also
affect the sickness funds' decisions on requests for reimbursement and thus
patient access to new technologies in general. OBJECTIVES: The aim of this study
was to identify the technologies that have repeatedly generated court actions and
whether these actions have been successful. The focus was on differences between
sectors, technology groups and indications. Based on this, we analysed in a case
study whether judicial decisions on the reimbursement of the same technologies
vary across the years. MATERIAL AND METHODS: Based on a systematic review, we
identified judicial decisions of German social courts on new technologies for the
years 2011 to 2016. The analysis included social court decisions on
reimbursements for technologies used in the treatment of individual patients.
RESULTS: 284 judicial decisions on new technologies were considered in the
analysis. In one third of the cases, the sickness funds were required to
reimburse the costs, with a higher percentage in inpatient than in outpatient
care. Technologies used in treatment of diseases of the eyes and the ears were
granted most frequently. In cases involving similar circumstances the social
courts sometimes came to conflicting decisions; these decisions are, in part,
contradictory to subsequent assessments by the Joint Federal Committee (G-BA).
CONCLUSIONS: Decisions as to whether reimbursement for new technologies is
granted or not do not appear to follow a systematic approach. In the context of
the seemingly innovation-friendly policy in inpatient care, there is uncertainty
with regard to the "generally accepted state of medical knowledge." It is
problematic for both patients and their treating physicians that over a number of
years legal proceedings are being initiated for technologies that have not been
subjected to a systematic assessment of their benefit.
PMID- 29331281
TI - [Do online ratings reflect structural differences in healthcare? The example of
German physician-rating websites].
AB - BACKGROUND: Previous surveys have shown that patient satisfaction varies with the
regional supply of physicians. Online ratings on physician-rating websites
represent a relatively new instrument to display patient satisfaction results.
The aim of this study was (1) to assess the current state of online ratings for
two medical disciplines (dermatologists and ear, nose and throat (ENT)
specialists), and (2) to analyze online derived patient satisfaction results
according to the physician density in Germany. METHODS: We collected online
ratings for 420 dermatologists and 450 ear, nose, and throat (ENT) specialists on
twelve German physician-rating websites. We analyzed the online ratings according
to the physician density (low, medium, high physician density). For this purpose,
we collected secondary data from both physician-rating websites and the regional
associations of statutory health insurance physicians. Data analysis was
performed using Median tests and Chi-square tests. RESULTS: In total, 10,239
online ratings for dermatologists and 8,168 online ratings for ENT specialists
were analyzed. Almost all dermatologists (99.3 %) and ENT specialists (98.9 %)
were listed on one of the physician-rating websites. A total of 93.5 % of all
listed dermatologists and 96.9 % of ENT-specialists were rated on at least one of
the physician-rating websites. Significant differences were found in the
distribution (i.e., percentage of listed or rated physicians) of the ratings
according to the regional physician density on only one physician-rating website
(p<0.001). Furthermore, online ratings were shown to be better in regions with a
higher physician density on two physician-rating website. On jameda.de, for
example, dermatologist ratings were better in regions with a higher physician
density compared to regions with a lower number of physicians (average rating:
2.16 vs. 2.67; p<0.001). CONCLUSIONS: Online ratings of dermatologists and ENT
specialists hardly differ in terms of regional physician density. Physician
rating websites thus do not appear to be appropriate to mirror differences in the
health service delivery structure. Our findings thus do not confirm the results
from previously published studies.
PMID- 29331283
TI - The influx of marine debris from the Great Japan Tsunami of 2011 to North
American shorelines.
AB - Marine debris is one of the leading threats to the ocean and the Great East Japan
Earthquake and tsunami on March 11, 2011 washed away an estimated 5million tons
of debris in a single, tragic event. Here we used shoreline surveys, disaster
debris reports and ocean drift models to investigate the temporal and spatial
trends in the arrival of tsunami marine debris. The increase in debris influx to
surveyed North American and Hawaiian shorelines was substantial and significant,
representing a 10 time increase over the baseline in northern Washington State
where a long term dataset was available. The tsunami event brought different
types of debris along the coast, with high-windage items dominant in Alaska and
British Columbia and large, medium-windage items in Washington State and Oregon.
Recorded cumulative debris landings to North America were close to 100,000 items
in the four year study period. The temporal peaks in measured shoreline debris
and debris reports match the ocean drift model solutions. Mitigation and
monitoring activities, such as shoreline surveys, provide crucial data and
monitoring for potential impacts should be continued in the future.
PMID- 29331282
TI - Development, Testing, and Implementation of a Training Curriculum for
Nonphysician Health Workers to Reduce Cardiovascular Disease.
AB - BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death worldwide.
The need to address CVD is greatest in low- and middle-income countries where
there is a shortage of trained health workers in CVD detection, prevention, and
control. OBJECTIVES: Based on the growing evidence that many elements of chronic
disease management can be shifted to nonphysician health care workers (NPHW), the
HOPE-4 (Heart Outcomes Prevention and Evaluation Program) aimed to develop, test,
and implement a training curriculum on CVD prevention and control in Colombia,
Malaysia, and low-resource settings in Canada. METHODS: Curriculum development
followed an iterative and phased approach where evidence-based guidelines,
revised blood pressure treatment algorithms, and culturally relevant risk factor
counseling were incorporated. Through a pilot-training process with high school
students in Canada, the curriculum was further refined. Implementation of the
curriculum in Colombia, Malaysia, and Canada occurred through partner
organizations as the HOPE-4 team coordinated the program from Hamilton, Ontario,
Canada. In addition to content on the burden of disease, cardiovascular system
pathophysiology, and CVD risk factors, the curriculum also included evaluations
such as module tests, in-class exercises, and observed structured clinical
examinations, which were administered by the local partner organizations. These
evaluations served as indicators of adequate uptake of curriculum content as well
as readiness to work as an NPHW in the field. RESULTS: Overall, 51 NPHW
successfully completed the training curriculum with an average score of 93.19% on
module tests and 84.76% on the observed structured clinical examinations. Since
implementation, the curriculum has also been adapted to the World Health
Organization's HEARTS Technical Package, which was launched in 2016 to improve
management of CVD in primary health care. CONCLUSIONS: The robust curriculum
development, testing, and implementation process described affirm that NPHW in
diverse settings can be trained in implementing measures for CVD prevention and
control.
PMID- 29331285
TI - Reply.
PMID- 29331284
TI - Effects of an experimental heat wave on fatty acid composition in two
Mediterranean seagrass species.
AB - Global warming is emerging as one of the most critical threats to terrestrial and
marine species worldwide. This study assessed the effects of simulated warming
events in culture on two seagrass species, Posidonia oceanica and Cymodocea
nodosa, which play a key role in coastal ecosystems of the Mediterranean Sea.
Changes in fatty acids as key metabolic indicators were assessed in specimens
from two geographical populations of each species adapted to different in situ
temperature regimes. Total fatty acid (TFA) content and composition were compared
in C. nodosa and P. oceanica from natural populations and following exposure to
heat stress in culture. After heat exposure, individuals of C. nodosa and P.
oceanica adapted to colder temperatures in situ accumulated significantly more
TFA than controls. For both species, the proportion of polyunsaturated fatty
acids (PUFA) decreased, and the percentage of saturated fatty acids (SFA)
increased significantly after the heat treatment. These results highlight that
populations of both species living at warmest temperatures in situ were more
thermo-tolerant and exhibited a greater capacity to cope with heat stress by
readjusting their lipid composition faster. Finally, exposure of seagrasses to
warmer conditions may induce a decrease in PUFA/SFA ratio which could negatively
affect their nutritional value and generate important consequences in the healthy
state of next trophic levels.
PMID- 29331286
TI - Re: Characteristics of a Mild Traumatic Brain Injury Sample Recruited Using
Amazon's Mechanical Turk.
PMID- 29331287
TI - Characterizing the effects of deep brain stimulation with magnetoencephalography:
A review.
AB - BACKGROUND: Deep brain stimulation (DBS) is an important form of neuromodulation
that is being applied to patients with motor, mood, or cognitive circuit
disorders. Despite the efficacy and widespread use of DBS, the precise mechanisms
by which it works remain unknown. Over the last decade, magnetoencephalography
(MEG) has become an important functional neuroimaging technique used to study
DBS. OBJECTIVE: This review summarizes the literature related to the use of MEG
to characterize the effects of DBS. METHODS: Peer reviewed literature on DBS-MEG
was obtained by searching the publicly accessible literature databases available
on PubMed. The abstracts of all reports were scanned and publications which
combined DBS-MEG in human subjects were selected for review. RESULTS: A total of
32 publications met the selection criteria, and included studies which applied
DBS for Parkinson's disease, dystonia, chronic pain, phantom limb pain, cluster
headache, and epilepsy. DBS-MEG studies provided valuable insights into network
connectivity, pathological coupling, and the modulatory effects of DBS.
CONCLUSIONS: As DBS-MEG research continues to develop, we can expect to gain a
better understanding of diverse pathophysiological networks and their response to
DBS. This knowledge will improve treatment efficacy, reduce side-effects, reveal
optimal surgical targets, and advance the development of closed-loop
neuromodulation.
PMID- 29331288
TI - Hallux Valgus Evaluation on MRI: Can Measurements Validated on Radiographs Be
Used?
AB - Hallux valgus (HV) is a common deformity of the great toe affecting >23% of
adults in the United States. The severity of the deformity is traditionally
analyzed using radiographs to determine measurements such as the HV and
intermetatarsal angles. We sought to determine the relationship between the
radiographic and magnetic resonance imaging (MRI) measurements because this is
not yet known. Two of us analyzed a series of 56 consecutive patients who had had
radiographs and MRI performed on the same foot between April 27, 2015 and March
9, 2016 and who satisfied all other inclusion and exclusion criteria (age 18 to
100 years, no history of recent foot trauma, and no metal hardware in the foot).
We found excellent interreader reliability (intraclass correlation 0.89 to 0.96)
and intermodality agreement (intraclass correlation 0.83 to 0.91). The HV angle
measured 15.0 degrees +/- 8.8 degrees on the MRI scans and 13.8 degrees +/-
8.7 degrees on the radiographs (mean difference -1.15 degrees +/- 3.89 degrees
), and the intermetatarsal angle was 9.0 degrees +/- 3.1 degrees on the MRI
scans and 8.8 degrees +/- 2.9 degrees on the radiographs (mean difference -0.22
degrees +/- 2.10 degrees ). The HV measurements were reliable on both
radiographs and MRI for the range of values tested. Small intermodality
statistically significant differences in HV angle measurements were found;
however, these might not be enough to be clinically significant.
PMID- 29331289
TI - Titanium Scaffolding: An Innovative Modality for Salvage of Failed First Ray
Procedures.
AB - Shortening of the first ray is a potential complication associated with first
metatarsal procedures. Correction of this deformity conventionally has required
the use of a tricortical bone graft to lengthen the bone. Graft complications,
including donor site morbidity, poor graft stability, and graft resorption, have
revealed a need for an alternative procedure. The present report shows that
titanium cage scaffolding has lower extremity applications beyond its previous
uses in the ankle and spine. Two patients underwent surgical correction for
failed first ray procedures using a titanium cage apparatus with a calcaneal
autograft and other biologic agents. The scaffolds were appropriately sized to
fill the defect. Patients remained non-weightbearing until radiographic evidence
of healing appeared. Success was determined by diminished pain, a return to
activity, ambulation, and patient satisfaction. Patients exhibited faster-than
anticipated healing, including a return to protected weightbearing activities and
increased stability within 6 weeks. Titanium cage implants provide long-term
stability and resistance to stress and strain in the forefoot. The implant we
have described, newly applied to the first ray, is analogous to a system used in
salvage of failed ankle replacements. In addition to reducing reliance on the
iliac crest bone graft, the titanium cage apparatus is advantageous because it is
customized to fill a defect using computed tomography scanning, thereby reducing
graft failure secondary to an improper shape. These cases demonstrate the
potential beneficial applications for titanium cages in failed first ray
reconstruction.
PMID- 29331290
TI - The Use of Ultrasonography to Identify the Intersection of the Dorsomedial
Cutaneous Nerve of the Hallux and the Extensor Hallucis Longus Tendon: A
Cadaveric Study.
AB - Terminal branches of the superficial fibular nerve are at risk of iatrogenic
damage during foot surgery, including hallux valgus rigidus correction,
bunionectomy, cheilectomy, and extensor hallucis longus tendon transfer. One
terminal branch, the dorsomedial cutaneous nerve of the hallux, is particularly
at risk of injury at its intersection with the extensor hallucis longus tendon.
Iatrogenic injuries of the dorsomedial cutaneous nerve of the hallux can result
in sensory loss, neuroma formation, and/or debilitating causalgia. Therefore,
preoperative identification of the nerve is of great clinical importance. The
present study used ultrasonography to identify the intersection between the
dorsomedial cutaneous nerve of the hallux and the extensor hallucis longus tendon
in cadavers. On ultrasound identification of the intersection, dissection was
performed to assess the accuracy of the ultrasound screening. The method
successfully pinpointed the nerve in 21 of 28 feet (75%). The sensitivity,
positive likelihood ratio, and positive and negative predictive values of
ultrasound identification of the junction of the dorsomedial cutaneous nerve and
the extensor hallucis longus tendon were 75%, 75%, 100%, and 0%, respectively. We
have described an ultrasound protocol that allows for the preoperative
identification of the dorsomedial cutaneous nerve of the hallux as it crosses the
extensor hallucis longus tendon. The technique could potentially be used to
prevent the debilitating iatrogenic injuries known to occur in association with
many common foot surgeries.
PMID- 29331292
TI - [Ocular melanocytosis].
PMID- 29331291
TI - Global MicroRNA Profiling in Human Bone Marrow Skeletal-Stromal or Mesenchymal
Stem Cells Identified Candidates for Bone Regeneration.
AB - Bone remodeling and regeneration are highly regulated multistep processes
involving posttranscriptional regulation by microRNAs (miRNAs). Here, we
performed a global profiling of differentially expressed miRNAs in bone-marrow
derived skeletal cells (BMSCs; also known as stromal or mesenchymal stem cells)
during in vitro osteoblast differentiation. We functionally validated the
regulatory effects of several miRNAs on osteoblast differentiation and identified
15 miRNAs, most significantly miR-222 and miR-423, as regulators of
osteoblastogenesis. In addition, we tested the possible targeting of miRNAs for
enhancing bone tissue regeneration. Scaffolds functionalized with miRNA nano
carriers enhanced osteoblastogenesis in 3D culture and retained this ability at
least 2 weeks after storage. Additionally, anti-miR-222 enhanced in vivo ectopic
bone formation through targeting the cell-cycle inhibitor CDKN1B (cyclin
dependent kinase inhibitor 1B). A number of additional miRNAs exerted additive
osteoinductive effects on BMSC differentiation, suggesting that pools of miRNAs
delivered locally from an implanted scaffold can provide a promising approach for
enhanced bone regeneration.
PMID- 29331294
TI - [Study of the results scleral-fixated intraocular lenses in the absence of
capsular support].
AB - INTRODUCTION: In the absence of sufficient capsular support, scleral fixation of
the intraocular lens is an interesting alternative. The goal is to evaluate this
implantation technique when traditional implantation is impossible. PATIENTS AND
METHODS: This is an observational, retrospective, monocentric study at the Amiens
university medical center between August 2013 and March 2016. Patients all
underwent scleral fixation of a three-piece implant without suturing of the
haptics, after posterior vitrectomy. All patients requiring implantation in the
absence of stable capsular support were included. Patients with adequate iris or
capsular support were excluded from our study. RESULTS: Eighteen patients were
included, with an average age of 69.3+/-16.9 years. The surgical indications
were: complicated surgery, trauma and endothelial decompensation. The
preoperative mean corrected visual acuity was 1.2+/-0.4 LogMAR while the
postoperative acuity was 0.7+/-0.5 LogMAR. The mean postoperative corneal
astigmatism was 1.9+/-1.9 diopters. The main complications observed were ocular
hypertension, macular edema, retinal detachment, iris incarceration and
exteriorization of the haptic. DISCUSSION: There are two alternatives when faced
with lack of a sufficient capsular support: scleral fixation or iris fixation.
Our technique is the only one achievable in the presence of iris atrophy.
Furthermore, it induces less astigmatism and enables the repositioning of a three
piece implant dislocated into the vitreous. CONCLUSION: Scleral fixation is a
technique allowing both a satisfactory and a lasting functional result and is to
be considered when faced with a lack of sufficient capsular support.
PMID- 29331293
TI - Toric lens implantation in cataract surgery: Automated versus manual horizontal
axis marking, analysis of 50 cases.
AB - SUBJECT: The main objective of our study was to evaluate the contribution of
automated conjunctival registration in the alignment of toric intraocular lenses
by comparing automated registration optimized with Callisto(r) to manual marking
of the horizontal axis. MATERIALS AND METHODS: We performed a prospective,
descriptive, monocentric study on patients undergoing cataract surgery with a
toric intraocular lens (Asphina 709 Zeiss), performed by a surgeon with good
experience in toric implants, between September 2016 and March 2017. We analyzed
the agreement between the manual marking of the 0-180 degrees axis versus the
one automatically generated by the CallistoTM, as well as the alignment of the
IOL and the refractive results at 1 month. RESULTS: We included 50 eyes of 38
patients. The mean corrected astigmatism was 1,9 D. The mean difference between
the 2 axes was 4,7 degrees [0-12.3 degrees ]. Only 50 % of the preoperative
manual markings were consistent with the automated measurement (<5 degrees ). At
one month, the mean rotation recorded was 4,3 degrees [0-29 degrees ]. The
alignment was identical for 70 % (n=35) of the IOLs (<=5 degrees ). As for
residual subjective astigmatism, the mean was 0.58 D. The mean visual acuity
without correction was 8/10 and 55 % saw 10/10 without correction. DISCUSSION:
Refractive performance depends on preoperative measurement, correct alignment of
the IOL and its stability in the bag. Our study shows the value of automated
conjunctival registration in the determination of the intraoperative axis of
alignment, even with an experienced surgeon. This precision is essential for a
good refractive result, especially since residual astigmatism in the case of
misalignment will increase with the power of the implant. CONCLUSION: Our study
shows excellent refractive results, regardless of the initial astigmatism, using
automated alignment. Precision of toric implantation opens the way to toric
multifocal implantation under the best conditions.
PMID- 29331295
TI - Helicopter Mountain Rescue in Slovenia from 2011 to 2015.
AB - INTRODUCTION: The popularity of adventure recreation in wilderness areas across
the world continues to increase. Nevertheless, the risk of injury and illness
remains significant. The purpose of this study is to analyze the mountain rescue
operations performed in Slovenia between 2011 and 2015. METHODS: This
retrospective study reports mountain rescue operations documented by the
Slovenian National Mountain Rescue Association. The annual number of ground-based
and helicopter-based rescues were identified and compared. For 2015, the
indication for rescue and the severity of injury were also analyzed, specifically
for interventions requiring the use of a helicopter. RESULTS: From 2011 through
2015, the number of rescues remained consistent with an annual average of 413 (SD
+/-15; range, 393-434) rescues. However, the percentage of ground-based rescues
varied significantly year by year (P=0.016), with highest rate in 2014 (68%) and
the lowest in 2015 (56%). In 2015, 434 mountain rescue operations were reported
in Slovenia. Injury accounted for 44%, illness for 10%, and fatality for 9% of
the rescues. In 37%, no illness or injury was reported. Helicopter rescue was
used in 190 (44%) of all interventions. Among the 190 helicopter rescues, 49% of
patients had nonfatal injuries, 29% required no medical treatment, 15% had
illness, and 7% had fatal injuries. CONCLUSIONS: A significant number of mountain
rescue operations were conducted in Slovenia from 2011 through 2015. Most of
these were needed for injured, ill, or deceased persons. A notable number of
rescues in 2015 required a helicopter.
PMID- 29331296
TI - A Case of Autosplenectomy in Sickle Cell Trait Following an Exposure to High
Altitude.
AB - A 24-year-old man presented with acute abdominal pain upon ascent to moderate
altitude (3500 m). An immediate evaluation revealed a splenic infarct, and he was
evacuated to sea level. Upon recovery, he was sent back to 3500 m without
detailed etiological evaluation, whereupon he experienced recurrent episodes of
left-side subcostal pain. Imaging suggested autosplenectomy, and workup revealed
a negative thrombophilia profile but was positive for sickle cell trait (SCT).
Individuals with SCT can be asymptomatic until exposure to severe hypoxia, upon
which they can manifest clinically as sickle cell syndrome. We discuss the rare
presentation of autosplenectomy in a patient with previously undiagnosed SCT on
exposure to high altitude.
PMID- 29331297
TI - Elevation 3 mm: A Case of a Cardiac Emergency and Rescue on Mount Monadnock.
PMID- 29331298
TI - Spatiotemporal characterization of microdamage accumulation in rat ulnae in
response to uniaxial compressive fatigue loading.
AB - Repetitive fatigue loading can induce microdamage accumulation in bone matrix,
which results in impaired mechanical properties and increased fracture
susceptibility. However, the spatial distribution and time-variant process of
microdamage accumulation in fatigue-loaded skeleton, especially for linear
microcracks which are known to initiate bone remodeling, remain not fully
understood. In this study, the time-varying process of the morphology and
distribution of microcracks in rat ulnae subjected to uniaxial compressive
fatigue loading was investigated. Right forelimbs of thirty four-month-old male
Sprague-Dawley rats were subjected to one bout of cyclic ramp loading with 0.67
Hz at a normalized peak force of 0.055 N/g body weight for 6000 cycles, and the
contralateral left ulnae were not loaded as the control samples. Ten rats were
randomly euthanized on Days 3, 5, and 7 post fatigue loading. Our findings via
two-dimensional histomorphometric measurements based on basic fuchsin staining
and three-dimensional quantifications using contrast-enhanced micro-computed
tomography (MicroCT) with precipitated BaSO4 staining demonstrated that the
accumulation of linear microcracks (increase in the amount of linear microcracks)
on Day 5 was significantly higher than that on Day 3 and Day 7 post fatigue
loading. Our histological and histomorphometric results revealed that linear
microcrack density (Cr.Dn) in the tensile cortex at Days 3, 5 and 7 post fatigue
loading was significantly higher than that in the compressive side, whereas
linear microcrack length (Cr.Le) in the tensile cortex at Day 3 was significantly
lower than that in the compressive cortex. Our findings revealed that microcrack
accumulation exhibited a non-linear time-varying process at 3, 5 and 7 days post
axial compressive fatigue loading (with observable peak Cr.Dn at Day 5). Our
findings also revealed distinct distribution of microcrack density and morphology
in rat ulnae with tensile and compressive strains, as characterized by more
microcracks accumulated in tensile cortices, and longer cracks shown in
compressive cortices.
PMID- 29331299
TI - The regulatory roles of Notch in osteocyte differentiation via the crosstalk with
canonical Wnt pathways during the transition of osteoblasts to osteocytes.
AB - Osteocytes comprise more than 90% of the cells in bone and are differentiated
from osteoblasts via an unknown mechanism. Recently, it was shown that Notch
signaling plays an important role in osteocyte functions. To gain insights into
the mechanisms underlying the functions of Notch in regulating the transition of
osteoblasts to osteocytes, we performed a luciferase assay by cloning the
proximal E11 and dentin matrix acidic phosphoprotein 1 (DMP1) promotor regions
into pGluc-Basic 2 vectors, which were subsequently transfected into the IDG-SW3
(osteocytes), MC3T3 (osteoblasts) and 293T (non-osteoblastic cells) cell lines.
Two approaches were used to activate Notch signaling in vitro. One was a Notch1
extracellular antibody-coated cell culture plate, and the other was transfection
of a Hairy/Enhancer of Split 1 (Hes1) overexpression vector. The interaction
between the Notch and Wnt signaling pathways was probed by assessing the
expression of a series of phosphorylated proteins involved in the cascade of both
signaling pathways. Our data suggested that Notch signaling regulates E11
expression through Hes1 activity, while Hes1 solely did not initiate the
expression of DMP1. The regulatory function of E11 by Hes1 was not observed in
the 293T cell line, indicating a cell context-dependent manner of the Notch
signaling pathway. Additionally, we found that Notch inhibited Wnt signaling at
the late differentiation stage of osteocytes by both directly repressing
phosphorylated Akt and preventing the nuclear aggregation of beta-catenin. These
findings provide profound understandings of Notch's regulatory function in
osteocyte differentiation.
PMID- 29331300
TI - Cigarette smoking and hip volumetric bone mineral density and cortical volume
loss in older adults: The AGES-Reykjavik study.
AB - This study aimed to explore the relationships of several indicators of cigarette
smoking habits (smoking status, pack-years, age at smoking initiation and smoking
cessation) with quantitative computed tomographic (QCT)-derived proximal femur
bone measures (trabecular vBMD, integral vBMD and the ratio of cortical to total
tissue volume (cvol/ivol)) and with subsequent change in these measures over the
next five years. A total of 2673 older adults (55.9% women), aged 66-92 years at
baseline from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study,
who had two QCT scans of the hip were studied. In multivariable linear regression
models, compared to never-smokers, current smokers had lower cvol/ivol at
baseline and former-smokers had poorer measures on all outcomes (lower trabecular
vBMD, integral vBMD and cvol/ivol), even when adjusted for several potential
confounders. Further, among former smokers, those with higher pack-years had
worse bone outcomes and those with longer duration since smoking cessation had
better bone health at baseline. Analyses of change in bone measures revealed that
compared to never-smokers, current smokers had significantly greater loss of
trabecular vBMD, integral vBMD, and cvol/ivol. The regression models included
adjustment for sex, age, education, and baseline body mass index, creatinine, %
weight change from age 50, 25OHD, physical activity level, high-sensitive C
Reactive protein levels, alcohol and coffee consumption, history of diabetes
mellitus, arthritis, and respiratory diseases. In conclusion, both current and
former smoking showed adverse associations with bone health assessed with QCT.
Results suggest that current smoking in particular may aggravate the rate of bone
loss at older age and highlight implications for targeting this risk factor in
populations that present higher smoking prevalence and vulnerability to bone
fragility.
PMID- 29331302
TI - Bone matrix microdamage and vascular changes characterize bone marrow lesions in
the subchondral bone of knee osteoarthritis.
AB - INTRODUCTION: Bone marrow lesions (BMLs) in the subchondral bone in
osteoarthritis (OA) are suggested to be multifactorial, although the pathogenic
mechanisms are unknown. Bone metabolism and cardiovascular risk factors associate
with BML in epidemiologic studies. However, there are no studies at the tissue
level investigating the relationship between these processes and BML. The aim of
this study was to investigate the relationship between BMLs in the tibial plateau
(TP) of knee OA and bone matrix microdamage, osteocyte density and vascular
changes. METHODS: TP were obtained from 73 patients at total knee replacement
surgery and BMLs were identified ex vivo in TP tissue using MRI. Comparator 'No
BML' tissue was from matched anatomical sites to the BMLs. Quantitative
assessment was made of subchondral bone microdamage, bone resorption indices,
osteocyte cellularity, and vascular features. RESULTS: Several key parameters
were different between BML and No BML tissue. These included increased microcrack
burden (p = .01, p = .0001), which associated positively with bone resorption and
negatively with cartilage volume, and greater osteocyte numerical density (p =
.02, p = .01), in the subchondral bone plate and subchondral trabeculae,
respectively. The marrow tissue within BML zones contained increased arteriolar
density (p = .04, p = .0006), and altered vascular characteristics, in particular
increased wall thickness (p = .007) and wall:lumen ratio (wall thickness over
internal lumen area) (p = .001), compared with No BML bone. CONCLUSIONS:
Increased bone matrix microdamage and altered vasculature in the subchondral bone
of BMLs is consistent with overloading and vascular contributions to the
formation of these lesions. Given the important role of BMLs in knee OA, these
contributing factors offer potential targets for the treatment and prevention of
knee OA.
PMID- 29331303
TI - Clear, professional and accurate communication is key to success in all
activities.
PMID- 29331301
TI - Marrow adipose tissue imaging in humans.
AB - Bone strength is affected not only by bone mineral density (BMD) and bone
microarchitecture but also its microenvironment. Recent studies have focused on
the role of marrow adipose tissue (MAT) in the pathogenesis of bone loss.
Osteoblasts and adipocytes arise from a common mesenchymal stem cell within bone
marrow and many osteoporotic states, including aging, medication use, immobility,
over - and undernutrition are associated with increased marrow adiposity.
Advancements in imaging technology allow the non-invasive quantification of MAT.
This article will review magnetic resonance imaging (MRI)- and computed
tomography (CT)-based imaging technologies to assess the amount and composition
of MAT. The techniques that will be discussed are anatomic T1-weighted MRI, water
fat imaging, proton MR spectroscopy, single energy CT and dual energy CT.
Clinical applications of MRI and CT techniques to determine the role of MAT in
patients with obesity, anorexia nervosa, and type 2 diabetes will be reviewed.
PMID- 29331304
TI - Gender Representation in Urologic Subspecialties.
AB - OBJECTIVE: To examine associations between urologic subspecialization, surgeon
gender and practice patterns among certifying urologists over the last 13 years.
MATERIALS AND METHODS: Demographic data of certifying and recertifying urologists
(2004 to 2015) were obtained from the American Board of Urology. We investigated
gender-specific trends in self-reported practice type (academic practice, private
practice), subspecialization, and employment as a full-time vs part-time
physician, relative to certification year and cycle. RESULTS: Of 9140 urologists
applying for certification or recertification over the study period, 815 (8.9%)
were women. The largest proportion of female surgeon candidates (65.0%) was first
time certifiers. Women represented 16.7% of first-time certifying urologists (P <
.001) and reported practicing in academia more frequently (23.6%) compared with
13.7% of men (P < .001). Female surgeons identified as subspecialists in greater
numbers (46.4%) than their male counterparts (23.4%) across all certification
years and cycle cohorts (P < .001). Women reported subspecializing in female
urology (24.2%) and pediatrics (10.2%) at higher frequencies than their male
colleagues (4.6% and 3.1% respectively, both P < .001). Female and male surgeon
candidates requested certification in equal proportion in andrology and
infertility (P = .83) and endourology (3.6% female vs 5.8% male, P = .13),
however differed in oncology (4.2% female vs 7.2% male, P = .001). CONCLUSION: A
growing proportion of certifying urologists are women, with the greatest
enrichment among those seeking first-time certification. Since 2004, female
surgeons account for a disproportionate volume of urologists who practice in the
academic setting and identify as subspecialists.
PMID- 29331305
TI - TIGAR inhibits ischemia/reperfusion-induced inflammatory response of astrocytes.
AB - The inflammatory response of glial cells contributes to neuronal damage or repair
after brain ischemia/reperfusion insult. We previously demonstrated a protective
role of TP53-induced glycolysis and apoptosis regulator (TIGAR) in ischemic
neuronal injury through increasing the flow of pentose phosphate pathway (PPP).
The present study investigated the possible role of TIGAR in ischemia/reperfusion
induced inflammatory response of astrocytes. Male ICR mice were subjected to
middle cerebral artery occlusion for 2 h followed by 24 h reperfusion and
cultured primary astrocytes were subjected to oxygen glucose deprivation for 9 h
followed by 24 h reoxygenation (OGD/R). Adenoviral vectors were used to alter the
levels of TIGAR protein in brain and in culture primary astrocytes. We showed
that during the OGD/R insult the protein levels of TIGAR were rapidly increased
in astrocytes. Overexpression of TIGAR mediated increased the viability, levels
of NADPH and rGSH, and reduced intracellular reactive oxygen species (ROS) in
cultured primary astrocytes. Overexpression of TIGAR not only significantly
reduced infarct volume after stroke insult but also markedly reduced long-term
mortality and improved recovery of neurological functions. Overexpression of
TIGAR tempered OGD/R- or ischemia/reperfusion-induced the upregulation of
inducible nitric oxide synthase (iNOS), cyclooxygenases COX2 and the release of
pro-inflammatory cytokines interleukin 1 beta (IL-1beta) and tumor necrosis
factor-alpha (TNF-alpha), while TIGAR knockdown produced opposite effects on
these parameters. Moreover, Overexpression of TIGAR suppressed OGD/R-induced
degradation of IkappaBalpha and NF-kappaB nuclear translocation in cultured
primary astrocytes. The present study elucidates a novel mechanism by which TIGAR
protects neurons against ischemia/reperfusion injury.
PMID- 29331306
TI - Primary mucinous eccrine carcinoma of the buccal space: A case report and review
of the literature.
AB - IMPORTANCE: Mucinous eccrine carcinoma is a rare entity that most commonly
affects the head and neck. Due to its low frequency of occurrence, review of its
etiology, histopathology, and treatment strategies is beneficial to all
clinicians who may encounter similar appearing masses. OBSERVATION: An 84-year
old male presented with a blue mass on the left cheek. This mass started as a
small bump and grew significantly over one year. His primary care physician
monitored its growth and ultimately referred to an otolaryngologist. Imaging
findings revealed a multi-lobular solid and cystic left buccal lesion. FNA was
suggestive of low grade mucoepidermoid carcinoma. INTERVENTION: Patient underwent
surgical excision with primary closure of the defect. Frozen section was
consistent with low grade salivary malignancy. Final pathology revealed primary
mucinous eccrine carcinoma of the skin. CONCLUSIONS AND RELEVANCE: Mucinous
eccrine carcinoma is a rare entity commonly seen in the head and neck region.
Mucinous deposits to the skin from primaries elsewhere in the body are much more
common than primary lesions of the skin. Histology is a key component of the
diagnosis but full oncologic workup is required. Treatment typically includes
wide local excision with possible adjuvant chemotherapy or radiation for high
risk features.
PMID- 29331308
TI - A tribute in life to the world icon of the cardiology of heights: Dr. Dante
Penaloza from Peru.
PMID- 29331307
TI - Risk factors of sensorineural hearing loss in patients with unilateral safe
chronic suppurative otitis media.
AB - PURPOSE: Chronic suppurative otitis media (CSOM) is the major cause of hearing
impairment, especially conductive hearing loss. Few patients also had
sensorineural component, the sensorineural hearing loss (SNHL) in CSOM is
controversial, especially for safe mucosal type. This study aims to assess the
relationship between the frequency of SNHL development in patients with safe
mucosal CSOM and its relation to patient's age, sex, duration of disease, size of
perforation and different audiological findings. MATERIAL AND METHODS: This is a
prospective study conducted from June 2016 to June 2017 in a tertiary referral
hospital. 200 patients with unilateral mucosal type of CSOM with normal
contralateral ear were included in the study. The diseased ears were taken as
study ears and normal ears as control ears in all patients. Detailed otologic
history, clinical and audiometric findings were recorded and analyzed. Results
were statistically compared in all patients for both study and control ears using
different parameters. RESULTS: Twenty patients had an average bone conduction
threshold of all frequencies above 25dB, which implies SNHL (10%). The incidence
of SNHL was statistically significant at higher speech frequencies. The incidence
increased with the presence of Diabetes Mellitus, smoking, duration of disease,
presence of active discharge and the increase in size of perforation. However, it
is not age dependent and there was no difference between males and females.
CONCLUSION: Safe mucosal CSOM can cause SNHL with multiple predisposing factors.
PMID- 29331309
TI - What is the predictive value of ST segment depression in inferior leads in first
acute anterior myocardial infarction?
AB - BACKGROUND: Electrical phenomenon and remote myocardial ischemia are the main
factors of ST segment depression in inferior leads in acute anterior myocardial
infarction (AAMI). We investigated the prognostic value of the sum of ST segment
depression amplitudes in inferior leads in patients with first AAMI treated with
primary percutaneous coronary intervention. (PPCI). METHODS: In this prospective
analysis, we evaluated the in-hospital prognostic impact of the sum of ST segment
depression in inferior leads on 206 patients with first AAMI. Patients were
stratified by tertiles of the sum of admission ST segment depression in inferior
leads. Clinical outcomes were compared between those tertiles. RESULTS:
Univariate analysis revealed higher rate of in-hospital death for patients with
ST segment depression in inferior leads in tertile 3, as compared to patients in
tertile 1 (OR 9.8, 95% CI 1.5-78.2, p<0.001). After adjustment for baseline
variables, ST segment depression in inferior leads in tertile 3 was associated
with 5.7-fold hazard of in-hospital death (OR: 5.7, 95% CI 1.2-35.1, p<0.001).
Spearman rank correlation test revealed correlation between the sum of ST segment
depression amplitude in inferior leads and the sum of ST segment elevation
amplitude in V1-6, L1 and aVL. Multivessel disease and additional RCA stenosis
were also detected more often in tertile 3. CONCLUSION: The sum of ST segment
depression amplitude in inferior leads of admission ECG in patients with first
AAMI treated with PPCI provide an independent prognostic marker of in-hospital
outcomes. Our data suggest the sum of ST segment depression amplitude to be a
simple, feasible and clinically applicable tool for rapid risk stratification in
patients with first AAMI.
PMID- 29331310
TI - Blood eosinophil counts as a guide for COPD treatment strategies.
PMID- 29331311
TI - Prediction of mortality in patients with chronic obstructive pulmonary disease
with the new Global Initiative for Chronic Obstructive Lung Disease 2017
classification: a cohort study.
AB - BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD)
2017 classification separates the spirometric 1-4 staging from the ABCD groups
defined by symptoms and exacerbations. Little is known about how this new
classification predicts mortality in patients with chronic obstructive pulmonary
disease (COPD). We aimed to establish the predictive ability of the GOLD 2017
classification, compared with earlier classifications, for all-cause and
respiratory mortality, both when using its main ABCD groups and when further
subdividing according to spirometric 1-4 staging. METHODS: In this nationwide
cohort study, we enrolled patients with COPD with data available in the Danish
registry for COPD. To be included in this registry, individuals must have been
outpatients in hospital-based pulmonary clinics in Denmark. Eligible patients
were aged 30 years or older; had received a primary diagnosis of COPD
(International Classification of Diseases [ICD]-10 J44.X) or acute respiratory
failure (ICD-10 J96.X) in combination with COPD (ICD-10 J44.X) as a secondary
diagnosis; and had complete data on FEV1, body-mass index, modified Medical
Research Council dyspnoea scale score, and smoking status. We categorised
eligible patients with complete data according to the 2007, 2011, and 2017 GOLD
classifications at the first contact with an outpatient clinic. For the GOLD 2017
classification, we further subdivided the patients by spirometry into 16
subgroups (1A to 4D). We calculated adjusted hazard ratios (HRs) for all-cause
and respiratory mortality and compared the predictive ability of the three GOLD
classifications (2007, 2011, and 2017) using receiver operating curves. FINDINGS:
We enrolled 33 765 patients with COPD, who were outpatients in Danish hospitals
between Jan 1, 2008, and Nov 30, 2013, in the main cohort assessed for all-cause
mortality. 22 621 of these patients had data available on cause-specific
mortality (respiratory) and were included in a subcohort followed from Jan 1,
2008, to Dec 31, 2011. For the GOLD 2017 classification, 3 year mortality
increased with increasing exacerbations and dyspnoea from group A (all-cause
mortality 10.0%, respiratory mortality 3.0%) to group D (all-cause mortality
36.9%, respiratory mortality 18.0%). However, 3 year mortality was higher for
group B patients (all-cause mortality 23.8%, respiratory mortality 9.7%) than for
group C patients (all-cause mortality 17.4%, respiratory mortality 6.4%).
Compared with group A, adjusted HRs for all-cause mortality ranged from 2.05 (95%
CI 1.87-2.26) for group B, to 1.47 (1.31-1.65) for group C, and to 3.01 (2.75
3.30) for group D. Area under the curve for all-cause mortality was 0.61 (95% CI
0.60-0.61) for GOLD 2007, 0.61 (0.60-0.62) for GOLD 2011, and 0.63 (0.53-0.73)
for GOLD 2017. Area under the curve for respiratory mortality was 0.64 (0.62
0.65) for GOLD 2007, 0.63 (0.62-0.64) for GOLD 2011, and 0.65 (0.53-0.78) for
GOLD 2017. The GOLD 2017 classification based on ABCD groups only did not predict
mortality better than the earlier 2007 and 2011 GOLD classifications. However,
when 16 subgroups (1A to 4D) were defined, the new classification predicted
mortality more accurately than the previous systems (p<0.0001). INTERPRETATION:
We showed that the new GOLD 2017 ABCD classification does not predict all-cause
and respiratory mortality more accurately than the previous GOLD systems from
2007 and 2011. FUNDING: Danish Lung Association, Program for Clinical Research
Infrastructure.
PMID- 29331312
TI - Brighter than GOLD.
PMID- 29331313
TI - Predictors of exacerbation risk and response to budesonide in patients with
chronic obstructive pulmonary disease: a post-hoc analysis of three randomised
trials.
AB - BACKGROUND: The peripheral blood eosinophil count might help identify those
patients with chronic obstructive pulmonary disease (COPD) who will experience
fewer exacerbations when taking inhaled corticosteroids (ICS). Previous post-hoc
analyses have proposed eosinophil cutoffs that are both arbitrary and limited in
evaluating complex interactions of treatment response. We modelled eosinophil
count as a continuous variable to determine the characteristics that determine
both exacerbation risk and clinical response to ICS in patients with COPD.
METHODS: We analysed data from three AstraZeneca randomised controlled trials of
budesonide-formoterol in patients with COPD with a history of exacerbations and
available blood eosinophil counts. Patients with any history of asthma were
excluded. Negative binomial regression analysis was done using splines for
modelling of continuous variables to study the primary outcome of annual
exacerbation rate adjusted for exposure time and study design. The trials are
registered with ClinicalTrials.gov, NCT00206167, NCT00206154, and NCT00419744.
FINDINGS: 4528 patients were studied. A non-linear increase in exacerbations
occurred with increasing eosinophil count in patients who received formoterol
alone. At eosinophil counts of 0.10 * 109 cells per L or more, a significant
treatment effect was recorded for exacerbation reduction with budesonide
formoterol compared with formoterol alone (rate ratio 0.75, 95% CI 0.57-0.99;
pinteraction=0.015). Interactions were observed between eosinophil count and the
treatment effects of budesonide-formoterol over formoterol on St George's
Respiratory Questionnaire (pinteraction=0.0043) and pre-bronchodilator FEV1
(linear effect p<0.0001, pinteraction=0.067). Only eosinophil count and smoking
history were independent predictors of response to budesonide-formoterol in
reducing exacerbations (eosinophil count, pinteraction=0.013; smoking history,
pinteraction=0.015). INTERPRETATION: In patients with COPD treated with
formoterol, blood eosinophil count predicts exacerbation risk and the clinical
response to ICS. FUNDING: AstraZeneca.
PMID- 29331314
TI - Chloroquine inhibits autophagy and deteriorates the mitochondrial dysfunction and
apoptosis in hypoxic rat neurons.
AB - AIMS: Mitochondrial dysfunction (MD) and apoptosis in the neurons are associated
with neonatal hypoxic-ischemic (HI) encephalopathy (HIE). The present study was
to explore the influence of autophagy on the induction of MD and apoptosis in the
neurons in a neonatal HIE rats and in hypoxia-treated neurons in vitro. MATERIALS
AND METHODS: Ten-day-old HI rat pups were sacrificed for brain pathological
examination and immunohistochemical analysis. The induction of autophagy,
apoptosis and MD were also determined in the neurons under hypoxia, with or
without autophagy inhibitor, chloroquine (CQ) treatment. KEY FINDINGS: HI
treatment caused atrophy and apoptosis of neurons, with a significantly increased
levels of apoptosis- and autophagy-associated proteins, such as cleaved caspase 3
and the B subunit of autophagy-related microtubule-associated protein 1 light
chain 3 (LC3-B). in vitro experiments demonstrated that the hypoxia induced
autophagy in neurons, as was inhibited by CQ. The hypoxia-induced cytochrome c
release, cleaved caspase 3 and cleaved caspase 9 were aggravated by CQ. Moreover,
there were higher levels of reactive oxygen species, more mitochondrial
superoxide and less mitochondrial membrane potential in the CQ-treated neurons
under hypoxia than in the neurons singularly under hypoxia. SIGNIFICANCE:
Apoptosis and autophagy were induced in HI neonatal rat neurons, autophagy
inhibition deteriorates the hypoxia-induced neuron MD and apoptosis. It implies a
neuroprotection of autophagy in the hypoxic-ischemic encephalopathy.
Administration of autophagy inducer agents might be promising in HIE treatment.
PMID- 29331315
TI - Ethnobotany, phytochemistry and pharmacology of Arctotis arctotoides (L.f.) O.
Hoffm.: A review.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Arctotis arctotoides (Asteraceae) is part of the
genus Arctotis. Arctotis is an African genus of approximately 70 species that
occur widely in the African continent with diverse medicinal values. This plant
is used for the treatment of indigestion and catarrh of the stomach, epilepsy,
topical wounds and skin disorders among the ethnic groups in South Africa and
reported to have a wide spectrum of pharmacological properties. AIM OF THE
REVIEW: The aim of the present review is to appraise the botany, traditional
uses, phytochemistry, pharmacological potential, analytical methods and safety
issues of A. arctotoides. Additionally, this review will help to fill the
existing gaps in knowledge and highlight further research prospects in the field
of phytochemistry and pharmacology. MATERIALS AND METHODS: Information on A.
arctotoides was collected from various resources, including books on African
medicinal herbs and Zulu medicinal plants, theses, reports and the internet
databases such as SciFinder, Google Scholar, Pubmed, Scopus, Web of Science, and
Mendeley by using a combination of various meaningful keywords. This review
surveys the available literature of the species from 1962 to April 2017. RESULTS:
In vitro and in vivo studies of the medicinal properties of A. arctotoides were
reviewed. The main isolated and identified compounds were reported as
sesquiterpenes, farnesol derivatives, germacranolide, guaianolides and some
steroids, of which, nine were reported as antimicrobial. Monoterpenoids and
sesquiterpenoids were the predominant essential oil compound classes of the
leaves, flowers, stems and roots. The present review revealed potential
pharmacological properties such as anti-oxidant, antibacterial, antifungal and
anticancer activities of plant extracts as well as isolated compounds. Moreover,
the review reports the safety profile (toxicity) of the crude extracts that had
been screened on brine shrimps, rats and human cell lines. CONCLUSIONS: The
present review has focused on the phytochemistry, botany, ethnopharmacology,
biological activities and toxicological information of A. arctotoides. On the
basis of reported data, A. arctotoides has emerged as a good source of natural
medicine for the treatment of microbial infections, skin diseases, anti
inflammatory and anticancer agents and also provides new insights for further
isolation of new bioactive compounds, especially the discovery of antimicrobial,
anti-inflammatory and anticancer novel therapeutic lead drug molecules.
Additionally, intensive investigations regarding pharmacological properties,
safety assessment and efficacy with their mechanism of action could be future
research interests before starting clinical trials for medicinal practices.
PMID- 29331317
TI - Resting-state quantitative EEG characteristics of insomniac patients with
depression.
AB - Insomnia is known to show hyperarousal in the central nervous system. However,
depression that often coexists with insomnia exhibits hypo-activity in the
frontal lobe, which is very different from insomnia. In the present study, we
examined wake resting state EEG of insomniac patients with depression to
investigate whether they could be conceptualized as spectrum of insomnia or
significantly different from insomnia. We compared the absolute power values of
EEG spectra of three groups: 15 insomniacs with comorbid depression (CD), age-
and sex-matched 15 comorbid-free insomniacs (CFI), and 15 good sleep controls
(GSC). As a result, CD and CFI showed no significant difference in the EEG power
spectrum analysis. Compared with GSC, however, both CD and CFI groups showed
increased high frequency EEG amplitude. From these results, we have confirmed
that CD shows cortical hyperarousal similar to insomnia in the daytime resting
state. In conclusion, it would be reasonable to understood insomniac patients
experiencing depression as a continuum of insomnia patients.
PMID- 29331316
TI - Pharmacological activities of the organic extracts and fatty acid composition of
the petroleum ether extract from Haplophyllum tuberculatum leaves.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Haplophyllum tuberculatum is used in traditional
medicine to treat many disorders including inflammation and pain. The aim of this
study is to investigate the organic extracts from H. tuberculatum leaves against
inflammation, gastric ulcer and pain. MATERIALS AND METHODS: Acute toxicity was
studied in vivo to determine the toxic doses of the organic extracts. Anti
inflammatory activity was also evaluated in vivo using carrageenan-induced paw
edema in Wistar rats. Gastroprotective activity was tested using the HCl/ethanol
induced gastric ulcer test in rats. Peripheral and central analgesic activities
were assessed using the acetic acid-induced writhing test and the hot-plate
method, respectively. The chemical composition of the fatty acids in the
petroleum ether (PE) extract was determined with GC-MS. RESULTS: At 25, 50 and
100mg/kg PE extract was the most active against inflammation. Percentages
inhibition 5h after carrageenan-injection were 51.12; 86.71% and 96.92%,
respectively. The same extract at 100mg/kg showed good analgesic activities using
the acetic acid-induced writhing test and the hot-plate method. The chloroform,
ethyl acetate (EtOAc) and butanolic (n-BuOH) extracts exhibited strong anti
inflammatory, gastroprotective and analgesic activities at 100mg/kg. The GC-FID
analysis revealed that the PE extract was rich in gamma-linolenic acid (45.50%)
followed by palmitic acid (18.48%), linoleic acid (10.73%), erucic acid (4.72),
stearic acid (3.96%) and oleic acid (2.57%). CONCLUSION: The results of the
present study support the traditional use of the leaves of H. tuberculatum and
may possibly serve as prospective material for further development of safe new
phytochemical anti-inflammatory, gastroprotective and/or analgesic agents.
PMID- 29331319
TI - A histopathological and biochemical evaluation of oxidative injury in the sciatic
nerves of male rats exposed to a continuous 900-megahertz electromagnetic field
throughout all periods of adolescence.
AB - The effects on human health of the electromagnetic field (EMF) emitted by mobile
phones, used by approximately 7 billion people worldwide, have become an
important subject for scientific research. Studies have suggested that the EMF
emitted by mobile phones can cause oxidative stress in different tissues and age
groups. Young people in adolescence, a time period when risky behaviors and
dependences increase, use mobile phones more than adults. The EMF emitted by
mobile phones, which are generally carried in the pocket or in bags when not in
use, will very probably affect the sciatic nerve. No previous study has
investigated the effect of mobile phone use in adolescence on peripheral nerve.
This study was planned accordingly. Twenty-four male Sprague Dawley rats aged 21
days were divided equally into control (CGr), Sham (SGr) and EMF (EMFGr) groups.
No procedure was performed on CGr rats. EMFGr were exposed to the effect of a 900
megahertz (MHz) EMF for 1 h at the same time every day between postnatal days 21
59 (the entire adolescent period) inside a cage in the EMF apparatus. SGr rats
were placed inside the cage for 1 h every day without being exposed to EMF. All
rats were sacrificed at the end of the study period, and 1 cm sections of sciatic
nerve were extracted. Malondialdehyde (MDA), glutathione, catalase (CAT)
superoxide dismutase (SOD) values were investigated biochemically in half of the
right sciatic nerve tissues. The other halves of the nerve tissues were subjected
to routine histopathological tissue procedures, sectioned and stained with
hematoxylin and eosin (H&E) and Masson's trichrome. Histopathological evaluation
of slides stained with Masson's trichrome and H&E revealed a normal appearance in
Schwann cells and axons in all groups. However, there was marked thickening in
the epineurium of sciatic nerves from EMFGr rats. MDA, SOD and CAT levels were
higher in EMFGr than in CGr and SGr at biochemical analyses. Apoptotic index (AI)
analysis revealed a significant increase in the number of TUNEL (+) cells when
EMFGr was compared with CGr and SGr. In conclusion, our study results suggest
that continuous exposure to a 900-MHz EMF for 1 h throughout adolescence can
cause oxidative injury and thickening in the epineurium in the sciatic nerve in
male rats.
PMID- 29331318
TI - Developmental changes in the feedback related negativity from 8 to 14 years.
AB - The study examined age related changes in the magnitude of the Feedback Related
Negativity (FRN) in 8-14 year old children performing a variation of a Go/No-Go
task. Participants were presented with four stimuli and tasked with mapping each
of them either to a response or to a "no response" by trial and error guided by
feedback. Feedback was valid for two stimuli (Go and No-Go) and invalid (.5
positive; .5 negative feedback) for the other two stimuli. The amplitude of the
FRN was evaluated as a function of age separately for Go and No-Go trials. The
results indicated that while performance on valid Go trials improved with age,
accuracy on valid No-Go trials remained stable with age. FRN amplitude was found
to be inversely related to age such that smaller FRN amplitudes were observed in
older children even after controlling for variance in learning. Additionally, the
FRN was found as a predictor of post-learning performance on Go trials but not on
No-Go trials, regardless of age. These results do not provide support to the link
between the FRN and inhibition control as measured by No-Go performance, but do
suggest a link with other executive control abilities called for by the Go
condition.
PMID- 29331321
TI - This Month in AJP.
AB - The following highlights summarize research articles that are published in the
current issue of The American Journal of Pathology.
PMID- 29331320
TI - Zika, dengue and yellow fever viruses induce differential anti-viral immune
responses in human monocytic and first trimester trophoblast cells.
AB - Zika virus (ZIKV) is a mosquito-borne flavivirus associated with severe neonatal
birth defects, but the causative mechanism is incompletely understood. ZIKV
shares sequence homology and early clinical manifestations with yellow fever
virus (YFV) and dengue virus (DENV) and are all transmitted in urban cycles by
the same species of mosquitoes. However, YFV and DENV have been rarely reported
to cause congenital diseases. Here, we compared infection with a contemporary
ZIKV strain (FSS13025) to YFV17D and DENV-4 in human monocytic cells (THP-1) and
first-trimester trophoblasts (HTR-8). Our results suggest that all three viruses
have similar tropisms for both cells. Nevertheless, ZIKV induced strong type 1
IFN and inflammatory cytokine and chemokine production in monocytes and
peripheral blood mononuclear cells. Furthermore, ZIKV infection in trophoblasts
induced lower IFN and higher inflammatory immune responses. Placental
inflammation is known to contribute to the risk of brain damage in preterm
newborns. Inhibition of toll-like receptor (TLR)3 and TLR8 each abrogated the
inflammatory cytokine responses in ZIKV-infected trophoblasts. Our findings
identify a potential link between maternal immune activation and ZIKV-induced
congenital diseases, and a potential therapeutic strategy that targets TLR
mediated inflammatory responses in the placenta.
PMID- 29331322
TI - Expression level of risk genes of MHC class II is a susceptibility factor for
autoimmunity: New insights.
AB - To date, the study of the impact of major hystocompatibility complex on
autoimmunity has been prevalently focused on structural diversity of MHC
molecules in binding and presentation of (auto)antigens to cognate T cells.
Recently, a number of experimental evidences suggested new points of view to
investigate the complex relationships between MHC gene expression and the
individual predisposition to autoimmune diseases. Irrespective of the nature of
the antigen, a threshold of MHC-peptide complexes needs to be reached, as well as
a threshold of T cell receptors engaged is required, for the activation and
proliferation of autoantigen-reactive T cells. Moreover, it is well known that
increased expression of MHC class II molecules may alter the T cell receptor
repertoire during thymic development, and affect the survival and expansion of
mature T cells. Many evidences confirmed that the level of both transcriptional
and post-transcriptional regulation are involved in the modulation of the
expression of MHC class II genes and that both contribute to the predisposition
to autoimmune diseases. Here, we aim to focus some of these regulative aspects to
better clarify the role of MHC class II genes in predisposition and development
of autoimmunity.
PMID- 29331323
TI - Regulation of inflammatory factors by double-stranded RNA receptors in breast
cancer cells.
AB - Malignant cells are not the only components of a tumor mass since other cells
(e.g., fibroblasts, infiltrating leukocytes and endothelial cells) are also part
of it. In combination with the extracellular matrix, all these cells constitute
the tumor microenvironment. In the last decade the role of the tumor
microenvironment in cancer progression has gained increased attention and
prompted efforts directed to abrogate its deleterious effects on anti-cancer
therapies. The immune system can detect and attack tumor cells, and tumor
infiltrating lymphocytes (particularly CD8 T cells) have been associated with
improved survival or better response to therapies in colorectal, melanoma,
breast, prostate and ovarian cancer patients among others. Contrariwise, tumor
associated myeloid cells (myeloid-derived suppressor cells [MDSCs], dendritic
cells [DCs], macrophages) or lymphoid cells such as regulatory T cells can
stimulate tumor growth via inhibition of immune responses against the tumor or by
participating in tumor neoangiogenesis. Herewith we analyzed the chemokine
profile of mouse breast tumors regarding their capacity to generate factors
capable of attracting and sequestering DCs to their midst. Chemoattractants from
tumors were investigated by molecular biology and immunological techniques and
tumor infiltrating DCs were investigated for matched chemokine receptors. In
addition, we investigated the inflammatory response of breast cancer cells, a
major component of the tumor microenvironment, to double-stranded RNA
stimulation. By using molecular biology techniques such as qualitative and
quantitative PCR, PCR arrays, and immunological techniques (ELISA, cytokine
immunoarrays) we examined the effects of dsRNA treatment on the cytokine
secretion profiles of mouse and human breast cancer cells and non-transformed
cells. We were able to determine that tumors generate chemokines that are able to
interact with receptors present on the surface of tumor infiltrating DCs. We
observed that PRR signaling is able to modify the production of chemokines by
breast tumor cells and normal breast cells, thereby constituting a possible
player in shaping the profile of the leukocyte population in the TME.
PMID- 29331324
TI - Rectal culture-directed antibiotic prophylaxis before transrectal prostate
biopsy: Reduced infectious complications and healthcare costs.
AB - BACKGROUND: Transrectal ultrasound-guided prostate biopsy (TUPB) is associated
with infectious complications (ICs), which are related to a greater prevalence of
ciprofloxacin-resistant bacteria (CRB) in rectal flora. We examined the ICs that
occurred in 2 groups: A guided antibiotic prophylaxis (GP) group and an empiric
prophylaxis (EP) group. We assessed the financial impact of GP. MATERIAL AND
METHODS: The GP group was studied prospectively (June 2013 to July 2014). We
collected rectal cultures (RCs) before the TUPB, which were seeded on selective
media with ciprofloxacin to determine the presence of CRB. The patients with
sensitive bacteria were administered ciprofloxacin. Patients with resistant
bacteria were administered GP according to the RC antibiogram. The EP group was
studied retrospectively (January 2011 to June 2009). RCs were not performed, and
all patients were treated with ciprofloxacin as prophylaxis. The ICs in both
groups were recorded during a period no longer than 30 days following TUPB
(electronic medical history). RESULTS: Three hundred patients underwent TUPB, 145
underwent GP, and 155 underwent EP. In the GP group, 23 patients (15.86%)
presented CRB in the RCs. Only one patient (0.7%) experienced a UTI. In the EP
group, 26 patients (16.8%) experienced multiple ICs (including 2 cases of sepsis)
(P<.005). The estimated total cost, including the management of the ICs, was
?57,076 with EP versus ?4802.33 with GP. The average cost per patient with EP was
?368.23 versus ?33.11 with GP. GP achieved an estimated total savings of
?52,273.67. Six patients had to undergo GP to prevent an IC. CONCLUSIONS: GP is
associated with a marked decrease in the incidence of ICs caused by CRB and
reduced healthcare costs.
PMID- 29331325
TI - E-Health Care: Promise or Peril for Chronic Illness.
PMID- 29331326
TI - Cryptorchidism in Sweden: A Nationwide Study of Prevalence, Operative Management,
and Complications.
AB - OBJECTIVES: To review the cumulative prevalence, operative management, and
complications of treatment for cryptorchidism in Sweden. STUDY DESIGN: A
nationwide observational study from longitudinal register data of all Swedish
born boys 0-18 years of age, diagnosed with cryptorchidism from 2001 to 2014.
Primary outcomes were occurrence and age at primary surgery. Secondary outcomes
included type of procedure and surgical site infection. RESULTS: Of 20 375 boys
diagnosed with cryptorchidism in 2001-2014, 12 766 were surgically treated. The
cumulative childhood prevalence was 1.8% (95% CI, 1.5-2.0), with a higher
prevalence in boys born prematurely, small for gestational age, or with low birth
weight. The median age at treatment decreased from 6.2 years in 2001 to 3.4 years
in 2014 (P < .001). Still, 94.1% (95% CI, 92.7-95.6) had surgery after the
recommended 1 year of age in 2014. Variations in age at surgery between Swedish
counties were great (range, 2.9-5.9 years of age). There were no deaths within 30
days after surgery and the frequency of surgical site infection was low (1.4%;
95% CI, 1.1-1.6). CONCLUSIONS: The cumulative childhood prevalence of
cryptorchidism was high, and complications were rare. Few boys underwent surgery
in a timely manner according to clinical guidelines, and standards of care varied
considerably across the country. Further research and collective actions are
needed to improve the detection and management of congenital cryptorchidism.
PMID- 29331328
TI - Pilot Clinical Trial of High-Flow Oxygen Therapy in Children with Asthma in the
Emergency Service.
AB - OBJECTIVES: To assess the efficacy of high-flow nasal cannula (HFNC) oxygen
therapy and safety in children with asthma and moderate respiratory failure in
the emergency department (ED). STUDY DESIGN: This was a prospective randomized
pilot trial of children (aged 1-14 years) presenting to a tertiary academic
pediatric ED with moderate-to-severe asthma exacerbations between September 2012
and December 2015. Patients with a pulmonary score (PS) >=6 or oxygen saturation
<94% with a face mask despite initial treatment (salbutamol/ipratropium bromide
and corticosteroids) were randomized to HFNC or to conventional oxygen therapy.
Pharmacologic treatment was at the discretion of attending physicians. The
primary outcome was a decrease in PS >=2 in the first 2 hours. Secondary outcomes
included disposition, length of stay, and need for additional therapies. RESULTS:
We randomly allocated 62 children to receive either HFNC (n = 30) or standard
oxygen therapy (n = 32). Baseline patient characteristics were similar in the 2
groups. At 2 hours after the start of therapy, PS had decreased by >=2 points in
16 patients in the HFNC group (53%) compared with 9 controls (28%) (P = .01).
Between-group differences in disposition, length of stay, and need for additional
therapies were not significant. No side effects were reported. CONCLUSION: HFNC
appears to be superior to conventional oxygen therapy for reducing respiratory
distress within the first 2 hours of treatment in children with moderate-to
severe asthma exacerbation refractory to first-line treatment. Further studies
are needed to demonstrate its overall efficacy in the management of asthma and
respiratory failure in the ED. TRIAL REGISTRATION: EudraCT: 2012-001771-36.
PMID- 29331327
TI - A New Approach to Rare Diseases of Children: The Undiagnosed Diseases Network.
PMID- 29331329
TI - Terra Firma-Forme Dermatosis.
PMID- 29331330
TI - PC-FACS.
AB - PC-FACS (Fast Article Critical Summaries for Clinicians in Palliative Care)
provides hospice and palliative care clinicians with concise summaries of the
most important findings from more than 100 medical and scientific journals. If
you have colleagues who would benefit from receivingPC-FACS, please encourage
them to join the AAHPM at aahpm.org. Comments from readers are welcomed at pc
facs@aahpm.org.
PMID- 29331332
TI - HIV infection and its effects on the development of autoimmune disorders.
AB - More than 35 years have elapsed since the initial outbreak of the HIV/AIDS
epidemic and the status of a considerable number of patients has changed from a
fatal disorder to a chronic one where comorbidities including sarcoidosis and
autoimmune diseases have become relevant and dominant. HIV targets the immune
system leading to a state of immunodeficiency in a setting of immune activation
in which CD4+ T cell depletion plays a critical role. The onset, natural history
and course of HIV-associated autoimmune disease has dramatically changed
according to the stage of HIV infection and since the introduction of combined
anti-retroviral therapy. There are some issues that need further study regarding
therapy, especially when immunosuppressive drugs and biologic agents are under
consideration. Currently, biologic agents and others immunosuppressive agents are
recommended when patients have CD4+ T cell counts above 200 cells/mm3 and the HIV
viral activity is completely suppressed.
PMID- 29331334
TI - The Future of Our Specialty: Elevating Gynecologic Surgery.
PMID- 29331333
TI - Influences of conformations of peptides on stereoinversions and/or isomerizations
of aspartic acid residues.
AB - Recently, non-enzymatic stereoinversions of aspartic acid (Asp) residues in
proteins and peptides have been reported. Here, we performed replica exchange
molecular dynamics (REMD) simulations of model peptides (exon 6, 26A-1, and 26A
2) extracted from elastin to investigate their structural features, thereby
revealing the factor that influences stereoinversions. For REMD trajectories, we
calculated distances between carboxyl carbon in Asp and amide nitrogen in the (n
+ 1) residue (CN distances). Because bond formation between carbon and nitrogen
is indispensable to the formation of a succinimide intermediate the distance
between them seems to play an important role in stereoinversion. Moreover, we
calculated polar surface areas (PSAs) for the trajectories, finding that CN
distances and PSA were different for each peptide, with the longest CN distance
and smallest PSA observed for exon 6 peptide, where stereoinversion of Asp is the
slowest. Although the average CN distance was shorter for exon 26A-1 peptide than
for exon 26A-2 peptide, the number of conformations with CN distances <3.0 A was
greater for exon 26A-2 peptide than for exon 26A-1 peptide. Furthermore, PSA for
amide nitrogen of the (n + 1) residue was larger for exon 26A-2 peptide than for
exon 26A-1 peptide. These results indicated that the flexibility of Asp and (n +
1) residues and hydrophilicity of peptides, especially in the (n + 1) residue,
play important roles in the stereoinversion of Asp. This article is part of a
Special Issue entitled: D-Amino acids: biology in the mirror, edited by Dr.
Loredano Pollegioni, Dr. Jean-Pierre Mothet and Dr. Molla Gianluca.
PMID- 29331331
TI - Interaction of ceramides and tear lipocalin.
AB - The distribution of lipids in tears is critical to their function. Lipids in
human tears may retard evaporation by forming a surface barrier at the air
interface. Lipids complexed with the major lipid binding protein in tears, tear
lipocalin, reside in the bulk (aqueous) and may have functions unrelated to the
surface. Many new lipids species have been revealed through recent mass
spectrometric studies. Their association with lipid binding proteins has not been
studied. Squalene, (O-acyl) omega-hydroxy fatty acids (OAHFA) and ceramides are
examples. Even well-known lipids such as wax and cholesteryl esters are only
presumed to be unbound because extracts of protein fractions of tears were devoid
of these lipids. Our purpose was to determine by direct binding assays if the
aforementioned lipids can bind tear lipocalin. Lipids were screened for ability
to displace DAUDA from tear lipocalin in a fluorescence displacement assay. Di-
and tri-glycerides, squalene, OAHFA, wax and cholesterol esters did not displace
DAUDA from tear lipocalin. However, ceramides displaced DAUDA. Apparent
dissociation constants for ceramide-tear lipocalin complexes using fluorescent
analogs were measured consistently in the submicromolar range with 3 methods,
linear spectral summation, high speed centrifugal precipitation and standard
fluorescence assays. At the relatively small concentrations in tears, all
ceramides were complexed to tear lipocalin. The lack of binding of di- and tri
glycerides, squalene, OAHFA, as well as wax and cholesterol esters to tear
lipocalin is consonant with residence of these lipids near the air interface.
PMID- 29331335
TI - Corrigendum to "A review of postoperative pain assessment records of nurses?"
[Applied Nursing Research 38C (2017) 1-4].
PMID- 29331336
TI - UDP-sugar accumulation drives hyaluronan synthesis in breast cancer.
AB - Increased uptake of glucose, a general hallmark of malignant tumors, leads to an
accumulation of intermediate metabolites of glycolysis. We investigated whether
the high supply of these intermediates promotes their flow into UDP-sugars, and
consequently into hyaluronan, a tumor-promoting matrix molecule. We quantified
UDP-N-Acetylglucosamine (UDP-GlcNAc) and UDP-glucuronic acid (UDP-GlcUA) in human
breast cancer biopsies, the levels of enzymes contributing to their synthesis,
and their association with the hyaluronan accumulation in the tumor. The content
of UDP-GlcUA was 4 times, and that of UDP-GlcNAc 12 times higher in the tumors as
compared to normal glandular tissue obtained from breast reductions. The surge of
UDP-GlcNAc correlated with an elevated mRNA expression of glutamine-fructose-6
phosphate aminotransferase 2 (GFAT2), one of the key enzymes in the biosynthesis
of UDP-GlcNAc, and the expression of GFAT1 was also elevated. The contents of
both UDP-sugars strongly correlated with tumor hyaluronan levels. Interestingly,
hyaluronan content did not correlate with the mRNA levels of the hyaluronan
synthases (HAS1-3), thus emphasizing the role of the UDP-sugar substrates of
these enzymes. The UDP-sugars showed a trend to higher levels in ductal vs.
lobular cancer subtypes. The results reveal for the first time a dramatic
increase of UDP-sugars in breast cancer, and suggest that their high supply
drives the accumulation of hyaluronan, a known promoter of breast cancer and
other malignancies. In general, the study shows how the disturbed glucose
metabolism typical for malignant tumors can influence cancer microenvironment
through UDP-sugars and hyaluronan.
PMID- 29331339
TI - Cardiopulmonary hemodynamics and C-reactive protein as prognostic indicators in
compensated and decompensated cirrhosis.
AB - BACKGROUND & AIMS: The main stages of cirrhosis (compensated and decompensated)
have been sub-staged based on clinical, endoscopic, and portal pressure
(determined by the hepatic venous pressure gradient [HVPG]) features.
Vasodilation leading to a hyperdynamic circulatory state is central in the
development of a late decompensated stage, with inflammation currently considered
a key driver. We aimed to assess hepatic/systemic hemodynamics and inflammation
(by C-reactive protein [CRP]) among the different sub-stages of cirrhosis and to
investigate their interrelationship and prognostic relevance. METHODS: A single
center, prospective cohort of patients with cirrhosis undergoing per protocol
hepatic and right-heart catheterization and CRP measurement, were classified into
recently defined prognostic stages (PS) of compensated (PS1: HVPG >=6 mmHg but
<10 mmHg; PS2: HVPG >=10 mmHg without gastroesophageal varices; PS3: patients
with gastroesophageal varices) and decompensated (PS4: diuretic-responsive
ascites; PS5: refractory ascites) disease. Cardiodynamic states based on cardiac
index (L/min/m2) were created: relatively hypodynamic (<3.2), normodynamic (3.2
4.2) and hyperdynamic (>4.2). RESULTS: Of 238 patients, 151 were compensated (PS1
= 25; PS2 = 36; PS3 = 90) and 87 were decompensated (PS4 = 48; PS5 = 39). Mean
arterial pressure decreased progressively from PS1 to PS5, cardiac index
increased progressively from PS1-to-PS4 but decreased in PS5. HVPG, model for end
stage liver disease (MELD), and CRP increased progressively from PS1-to-PS5.
Among compensated patients, age, HVPG, relatively hypodynamic/hyperdynamic state
and CRP were predictive of decompensation. Among patients with ascites, MELD,
relatively hypodynamic/hyperdynamic state, post-capillary pulmonary hypertension,
and CRP were independent predictors of death/liver transplant. CONCLUSIONS: Our
study demonstrates that, in addition to known parameters, cardiopulmonary
hemodynamics and CRP are predictive of relevant outcomes, both in patients with
compensated and decompensated cirrhosis. LAY SUMMARY: There are two main stages
in cirrhosis, compensated and decompensated, each with a main relevant outcome.
In compensated cirrhosis the main relevant outcome is the development of ascites,
while in decompensated cirrhosis it is death. Major roles of cardiac dysfunction
and systemic inflammation have been hypothesized in the evolution of the disease
in decompensated patients. In this study, we have shown that these factors were
also involved in the progression from compensated to decompensated stage.
PMID- 29331338
TI - Adiponectin levels in Brazilian adolescents: Distribution and associated factors
in ERICA survey.
AB - BACKGROUND: The aim of this study was to evaluate the distribution of adiponectin
and associated factors with low adiponectin levels in a large sample of
adolescents from different Brazilian regions. METHODS: This is a national, school
based, cross-sectional multicenter study of cardiovascular risk factors in
Brazilian adolescents aged 12 to 17 years. Serum adiponectin levels (MUg/ml) were
measured by enzyme-linked immunosorbent assay kit. Given the lack of reference
values, sex-and age-specific median was adopted as the cutoff point, with the
values below the median representing a higher-risk profile. Associated factors
with low levels of adiponectin were investigated using Poisson regression.
RESULTS: The sample consisted of 4546 adolescents, the majority female (61.2%).
The prevalence of overweight/obesity and abdominal obesity was 30% and 13.4%,
respectively. The medians of adiponectin were 13.4 MUg/ml (95%CI: 12.8-14.0) in
males and 14.2 MUg/ml (95%CI: 13.3-15.0) in females. Lower adiponectin levels
were associated with both overweight (Prevalence Ratios (PR) = 1.17; 95%CI 1.01
1.36) and obesity (PR = 1.36; 95%CI 1.16-1.56) in males, while, in females,
adiponectin levels were associated only with obesity (PR = 1.45; 95% CI 1.26
1.66). Increased waist circumference in both males and females was inversely
associated with adiponectin level. CONCLUSIONS: Adiponectin levels were lower
among adolescents with weight excess and abdominal obesity. Male adolescents who
live in rural areas and study at private schools also showed lower adiponectin
concentrations.
PMID- 29331340
TI - Hsp72 protects against liver injury via attenuation of hepatocellular death,
oxidative stress, and JNK signaling.
AB - BACKGROUND & AIMS: Heat shock protein (Hsp) 72 is a molecular chaperone that has
broad cytoprotective functions and is upregulated in response to stress. To
determine its hepatic functions, we studied its expression in human liver
disorders and its biological significance in newly generated transgenic animals.
METHODS: Double transgenic mice overexpressing Hsp72 (gene Hspa1a) under the
control of a tissue-specific tetracycline-inducible system (Hsp72-LAP mice) were
produced. Acute liver injury was induced by a single injection of acetaminophen
(APAP). Feeding with either a methionine choline-deficient (MCD; 8 weeks) or a
3,5-diethoxycarbonyl-1,4-dihydrocollidine-supplemented diet (DDC; 12 weeks) was
used to induce lipotoxic injury and Mallory-Denk body (MDB) formation,
respectively. Primary hepatocytes were treated with palmitic acid. RESULTS:
Patients with non-alcoholic steatohepatitis and chronic hepatitis C infection
displayed elevated HSP72 levels. These levels increased with the extent of
hepatic inflammation and HSP72 expression was induced after treatment with either
interleukin (IL)-1beta or IL-6. Hsp72-LAP mice exhibited robust, hepatocyte
specific Hsp72 overexpression. Primary hepatocytes from these animals were more
resistant to isolation-induced stress and Hsp72-LAP mice displayed lower levels
of hepatic injury in vivo. Mice overexpressing Hsp72 had fewer APAP protein
adducts and were protected from oxidative stress and APAP-/MCD-induced cell
death. Hsp72-LAP mice and/or hepatocytes displayed significantly attenuated Jnk
activation. Overexpression of Hsp72 did not affect steatosis or the extent of MDB
formation. CONCLUSIONS: Our results demonstrate that HSP72 induction occurs in
human liver disease, thus, HSP72 represents an attractive therapeutic target
owing to its broad hepatoprotective functions. LAY SUMMARY: HSP72 constitutes a
stress-inducible, protective protein. Our data demonstrate that it is upregulated
in patients with chronic hepatitis C and non-alcoholic steatohepatitis. Moreover,
Hsp72-overexpressing mice are protected from various forms of liver stress.
PMID- 29331337
TI - Elastin in lung development and disease pathogenesis.
AB - Elastin is expressed in most tissues that require elastic recoil. The protein
first appeared coincident with the closed circulatory system, and was critical
for the evolutionary success of the vertebrate lineage. Elastin is expressed by
multiple cell types in the lung, including mesothelial cells in the pleura,
smooth muscle cells in airways and blood vessels, endothelial cells, and
interstitial fibroblasts. This highly crosslinked protein associates with
fibrillin-containing microfibrils to form the elastic fiber, which is the
physiological structure that functions in the extracellular matrix. Elastic
fibers can be woven into many different shapes depending on the mechanical needs
of the tissue. In large pulmonary vessels, for example, elastin forms continuous
sheets, or lamellae, that separate smooth muscle layers. Outside of the
vasculature, elastic fibers form an extensive fiber network that originates in
the central bronchi and inserts into the distal airspaces and visceral pleura.
The fibrous cables form a looping system that encircle the alveolar ducts and
terminal air spaces and ensures that applied force is transmitted equally to all
parts of the lung. Normal lung function depends on proper secretion and assembly
of elastin, and either inhibition of elastin fiber assembly or degradation of
existing elastin results in lung dysfunction and disease.
PMID- 29331341
TI - Effects of the gut-liver axis on ischaemia-mediated hepatocellular carcinoma
recurrence in the mouse liver.
AB - BACKGROUND & AIMS: There is growing evidence that liver graft ischemia
reperfusion (I/R) is a risk factor for hepatocellular carcinoma (HCC) recurrence,
but the mechanisms involved are unclear. Herein, we tested the hypothesis that
mesenteric congestion resulting from portal blood flow interruption induces
endotoxin-mediated Toll-like receptor 4 (Tlr4) engagement, resulting in elevated
liver cancer burden. We also assessed the role of remote ischemic preconditioning
(RIPC) in this context. METHODS: C57Bl/6j mice were exposed to standardized
models of liver I/R injury and RIPC, induced by occluding the hepatic and femoral
blood vessels. HCC was induced by injecting RIL-175 cells into the portal vein.
We further evaluated the impact of the gut-liver axis (lipopolysaccharide (LPS)
Tlr4 pathway) in this context by studying mice with enhanced (lipopolysaccharide
infusion) or defective (Tlr4-/- mice, gut sterilization, and Tlr4 antagonist)
Tlr4 responses. RESULTS: Portal triad clamping provoked upstream mesenteric
venous engorgement and increased bacterial translocation, resulting in aggravated
tumor burden. RIPC prevented this mechanism by preserving intestinal integrity
and reducing bacterial translocation, thereby mitigating HCC recurrence. These
observations were linked to the LPS-Tlr4 pathway, as supported by the high and
low tumor burden displayed by mice with enhanced or defective Tlr4 responses,
respectively. CONCLUSIONS: Modulation of the gut-liver axis and the LPS-Tlr4
response by RIPC, gut sterilization, and Tlr4 antagonism represents a potential
therapeutic target to prevent I/R lesions, and to alleviate HCC recurrence after
liver transplantation and resection. LAY SUMMARY: Cancer recurrence can occur
after liver resection or liver transplantation for hepatocellular carcinoma
(HCC). This study suggests that intestinal venous congestion, which often occurs
during liver surgery, favors the translocation of gut-derived bacterial products
in the portal vein, thereby facilitating cancer recurrence by enhancing the
signaling of Toll-like receptor 4 in the liver. Using a mouse model of HCC
recurrence, we show that strategies that (i) reduce bacterial translocation (by
gut decontamination, or by protecting the intestine from venous ischemia damage)
or (ii) inhibit Tlr4 signaling in the liver, could reduce cancer recurrence.
PMID- 29331342
TI - Development of a prognostic score to predict response to Yttrium-90
radioembolization for hepatocellular carcinoma with portal vein invasion.
AB - BACKGROUND & AIMS: Yttrium-90 transarterial radioembolization (TARE) has shown
promising efficacy in the treatment of patients with hepatocellular carcinoma
(HCC), associated with portal vein tumor thrombus (PVTT). The aim of this study
is to identify prognostic factors for survival in patients with HCC and PVTT
undergoing TARE, and build a prognostic classification for these patients.
METHODS: This is a single center retrospective study conducted over six years
(2010-2015), on consecutive patients undergoing TARE. Patients were included if
they met the following criteria: presence of at least one measurable HCC,
presence of PVTT not occluding the main portal trunk, absence of extrahepatic
metastases, Child-Pugh score within B7, Eastern Cooperative Oncology Group
performance status 0-1. Uni- and multivariable analysis was used to explore the
variables that showed an independent relationship with survival. A prognostic
score was then derived, and three prognostic categories were identified. RESULTS:
A total of 120 patients were included in the study. Median overall survival (OS)
was 14.1 months (95% CI 10.7-17.5) and median progression-free survival (PFS) was
6.5 months (95% CI 3.8-9.2). The only variables independently correlated with OS
were bilirubin, extension of PVTT and tumor burden. Three prognostic categories
were identified: favourable prognosis (0 points), intermediate prognosis (2-3
points) and dismal prognosis (>3 points). Median OS in the three categories was
32.2 months, 14.9 months and 7.8 months respectively (p <0.0001). PFS (p = 0.045)
and the risk of liver decompensation (p <0.0001) also significantly differed
along the same prognostic categories. CONCLUSIONS: Radioembolization with Yttrium
90 is an effective therapy for patients with HCC and PVTT. The proposed
prognostic stratification may help to better identify good candidates for the
treatment, and those for whom TARE may be futile. LAY SUMMARY: Yttrium-90
transarterial radioembolization (TARE) is a microembolic procedure that minimizes
alterations to hepatic arterial flow, and thus can be safely performed in
patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus
(PVTT). In this study, we retrospectively evaluated the independent predictors of
long-term outcomes in patients with HCC and PVTT treated with TARE. Bilirubin
level, extension of PVTT and tumor burden were independently related to post
treatment survival: the combination of these factors allowed us to build a
prognostic stratification that may help to better identify good candidates for
the treatment, and those for whom TARE may be futile.
PMID- 29331344
TI - Feels Not Right Stabbing a Child.
PMID- 29331343
TI - Irradiation stents vs. conventional metal stents for unresectable malignant
biliary obstruction: A multicenter trial.
AB - BACKGROUND & AIMS: Placement of an irradiation stent has been demonstrated to
offer longer patency and survival than an uncovered self-expandable metallic
stent (SEMS) in patients with unresectable malignant biliary obstruction (MBO).
We aim to further assess the efficacy of an irradiation stent compared to an
uncovered SEMS in those patients. METHODS: We performed a randomized, open-label
trial of participants with unresectable MBO at 20 centers in China. A total of
328 participants were allocated in parallel to the irradiation stent group (ISG)
or the uncovered SEMS group (USG). Endpoints included stent patency (primary),
technical success, relief of jaundice, overall survival, and complications.
RESULTS: The first quartile stent patency time (when 25% of the patients
experienced stent restenosis) was 212 days for the ISG and 104 days for the USG.
Irradiation stents were significantly associated with a decrease in the rate of
stent restenosis (9% vs. 15% at 90 days; 16% vs. 27% at 180 days; 21% vs. 33% at
360 days; p = 0.010). Patients in the ISG obtained longer survival time (median
202 days vs. 140 days; p = 0.020). No significant results were observed in
technical success rate (93% vs. 95%; p = 0.499), relief of jaundice (85% vs. 80%;
p = 0.308), and the incidence of grade 3 and 4 complications (8.5% vs. 7.9%; p =
0.841). CONCLUSIONS: Insertion of irradiation stents instead of uncovered SEMS
could improve patency and overall survival in patients with unresectable MBO. LAY
SUMMARY: For patients with unresectable malignant biliary obstruction (MBO),
placement of a self-expandable metallic stent (SEMS) is a recommended palliative
modality to relieve pruritus, cholangitis, pain, and jaundice. However,
restenosis is a main pitfall after stent placement. Data from this first
multicenter randomized controlled trial showed that insertion of an irradiation
stent provided longer patency and better survival than a conventional metal
stent. ClinicalTrials.gov ID: NCT02001779.
PMID- 29331345
TI - July 14, 2016, Terror Attack in Nice, France.
AB - On July 14, 2016, a terrorist attack by truck occurred in Nice, France, during
the traditional fireworks for Bastille Day. The authors present the point of view
of the doctors from Lenval University Children's Hospital, which is located near
the attack place and which had to manage 47 casualties, including 12 adults.
PMID- 29331346
TI - Predicting Low-Resource-Intensity Emergency Department Visits in Children.
AB - OBJECTIVES: Interventions to reduce frequent emergency department (ED) use in
children are often limited by the inability to predict future risk. We sought to
develop a population-based model for predicting Medicaid-insured children at risk
for high frequency (HF) of low-resource-intensity (LRI) ED visits. METHODS: We
conducted a retrospective cohort analysis of Medicaid-insured children (aged 1-18
years) included in the MarketScan Medicaid database with >=1 ED visit in 2013.
LRI visits were defined as ED encounters with no laboratory testing, imaging,
procedures, or hospitalization; and HF as >=3 LRI ED visits within 365 days of
the initial encounter. A generalized linear regression model was derived and
validated using a split-sample approach. Validity testing was conducted examining
model performance using 3 alternative definitions of LRI. RESULTS: Among 743,016
children with >=1 ED visit in 2013, 5% experienced high-frequency LRI ED use,
accounting for 21% of all LRI visits. Prior LRI ED use (2 visits: adjusted odds
ratio = 3.5; 95% confidence interval, 3.3, 3.7; and >=3 visits: adjusted odds
ratio = 7.7; 95% confidence interval, 7.3, 8.1) and presence of >=3 chronic
conditions (adjusted odds ratio = 1.7; 95% confidence interval, 1.6, 1.8) were
strongly associated with future HF-LRI ED use. A model incorporating patient
characteristics and prior ED use predicted future HF-LRI ED utilization with an
area under the curve of 0.74. CONCLUSIONS: Demographic characteristics and
patterns of prior ED use can predict future risk of HF-LRI ED use in the
following year. Interventions for reducing low-value ED use in these high-risk
children should be considered.
PMID- 29331347
TI - Empowering Post-Surgical Patients to Improve Opioid Disposal: A Before and After
Quality Improvement Study.
AB - BACKGROUND: Our country is in the midst of an opioid epidemic. Although the
problem is multifactorial, one issue is the presence of excess prescription
opioid medications circulating in our communities. Our objective was to determine
whether dissemination of an educational brochure would improve the disposal of
unused opioids after surgery. STUDY DESIGN: Eligible surgery patients from an
upper extremity/peripheral nerve clinic were enrolled into this prospective
before and after study between February 2017 and September 2017. Patients who
reported opioid use preoperatively were excluded from this study. The same survey
was administered to the group of patients who did not receive the intervention
and to those who did receive the intervention. Our primary endpoint was the
proportion of patients who disposed of unused opioid medications. RESULTS: A
total of 334 patients were studied: 164 who did not receive the brochure and 170
who received the brochure. Seventy-six patients were excluded for preoperative
opioid use. After dissemination of the brochure, there was a significant increase
in the proportion of patients who disposed of their unused opioids (11% vs 22%, p
= 0.02). Of those who disposed of their opioids, there was no significant
difference in the proportion of patients from each group who disposed in a manner
that was recommended by the brochure (43% vs 64%, p = 0.19). CONCLUSIONS:
Dissemination of the educational brochure improved disposal of unused opioids
after surgery. This low-cost, easily implemented intervention can improve
disposal of unused opioids and ultimately, decrease the amount of excess opioids
circulating in our communities.
PMID- 29331348
TI - Effects of l-tryptophan on the growth, intestinal enzyme activities and non
specific immune response of sea cucumber (Apostichopus japonicus Selenka) exposed
to crowding stress.
AB - In order to reveal the effects of l-tryptophan (Trp) on the physiology and immune
response of sea cucumber (Apostichopus japonicus Selenka) exposed to crowding
stress, four density groups of sea cucumbers (i.e. 4, 8, 16 and 32 individuals
per 40 L water, represented as L, ML, MH and H) were fed with diets containing 0,
1, 3 and 5% l-tryptophan respectively for 75 days. The results showed that the
specific growth rates (SGR) of the sea cucumber fed with diet with 3% Trp (L,
2.1; ML, 1.76; MH, 1.2; H, 0.7) were significantly higher than those fed with
basal diet without Trp supplementation (P < .05). Peak amylase activity occurred
at H stress density at 3% dietary Trp. Trypsin activity was higher in diet 3% in
ML and MH densities than the controls, which increased by 66.4% and 53.8%.
However, the lipase activity first increased and then decreased from the stocking
density L to H, with highest values of 3% Trp group showed the highest value than
other groups. Compared to those fed with the basal diet, sea cucumber fed diets
with Trp (3%) had significantly higher phagocytic activities (0.28 OD540/106
cells, H) in coelomic fluid and respiratory burst activities (0.105 OD630/106
cells, MH) (P < .05). The results suggested that Trp cannot improve superoxide
dismutase (SOD) activity at L, ML and MH densities. The alkaline phosphatase
activity (AKP) significantly decreased at H stress density. Under the
experimental conditions, the present results confirmed that a diet supplemented
with 3% Trp was able to enhance intestinal enzyme activities, non-specific immune
response and higher growth performance of A. japonicus.
PMID- 29331349
TI - Effect of a LECT2 on the immune response of peritoneal lecukocytes against Vibrio
anguillarum in roughskin sculpin.
AB - Leukocyte cell-derived chemotaxin 2 (LECT2) is a multi-functional protein that is
mainly synthesized by the liver. However, its role in roughskin scalping is less
known. Here, we cloned a leukocyte cell-derived chemotaxin 2 (TfLECT2) genes in
the liver of roughskin scalping, Trachidermus fasciatus, and studied its possible
role involved in the immune response against Vibrio anguillarum (V. anguillarum)
of peritoneal lecukocytes under in vivo conditions. The cDNA sequence of TfLECT2
is 566 bp in size. Its deduced amino acid (aa) sequence comprises 151 residues,
of which the first 16 residues form a putative signal peptide and 101 residues
compose a typical peptidase M23 domain in the C-terminal region. The domain
structure is conserved in all LECT2 proteins, which suggests a close phylogenetic
relationship between TfLECT2 and LECT2 in other fish species. Real-time
quantitative PCR analysis revealed that TfLECT2 gene expression was dramatically
increased in liver after V. anguillarum stimulation. Subsequently, TfLECT2 was
prokaryotic expressed and purified to prepare anti-TfLECT2 antibody. After V.
anguillarum challenge, leukocytes recruitment and LECT2 levels in peritoneal
exudates were increased, and positively correlated with each other. Moreover,
recombinant TfLECT2 administration significantly improved immune responses after
infection, principally in stimulating the recruitment, phagocytosis and
respiratory burst of leukocytes at the site of infection; however, anti-TfLECT2
treatment neutralized these abilities. Therefore, TfLECT2 may trigger the early
immune events of peritoneal leukocytes and it will be useful to induce innate
immune response of fish.
PMID- 29331350
TI - Construction of pOGOduet - An inducible, bicistronic vector for synthesis of
recombinant proteins in Corynebacterium glutamicum.
AB - The Gram-positive Corynebacterium glutamicum is widely known for its application
in the industrial production of amino acids and as a non-pathogenic model
organism for cell wall biosynthesis in the group of CMN bacteria. For
biotechnological and physiological studies often co-expression of recombinant
genes is required, however for C. glutamicum no vector for the independent co
expression of two genes was described. We here created the novel expression
vector pOGOduet for C. glutamicum, which carries the ColE1 replicon of E. coli
and the pBL1 replicon of C. glutamicum and two independently inducible promoters
Ptac and Ptet each followed by unique multiple cloning sites. Functionality of
pOGOduet is tested by coexpression of genes for the fluorescent proteins eCFP and
mVenus; fluorescence of the reporters varies in dependence of the inducer
concentrations present in the culture broth. These experiments demonstrate that
the vector pOGOduet fulfills the task for individually inducible expression of
two genes of interest in C. glutamicum.
PMID- 29331351
TI - Endoscopic surgery of the frontoethmoidal osteomas.
PMID- 29331352
TI - Factors associated with voice disorders among the elderly: a systematic review.
AB - INTRODUCTION: During the aging process, natural modifications occur in the larynx
and the structures involved in phonation which explain the specific
characteristics found in the voices of elderly persons. When, at any moment, a
voice fails and there is interference with communication, a voice disorder has
occurred. This can generate disadvantages in communicative efficiency and have a
negative impact on quality of life, compromising mechanisms of socialization, the
maintenance of autonomy, and the sense of well-being. Nevertheless, there appears
to be little clarity about which factors are associated with voice disorders in
this population, especially from an epidemiological perspective. OBJECTIVE: The
present study is a literature review to identify factors associated with voice
disorders among the elderly described in population-based studies. METHODS: A
systematic review of electronic databases was carried out. The methodological
quality of the studies was analyzed with the Strengthening the Reporting of
Observational Studies in Epidemiology guidelines. The research was conducted
independently by two researchers. RESULTS: Although two articles met the
eligibility criteria, none fulfilled all the criteria for the evaluation of
methodological quality. According to the two studies selected for this review,
factors associated with voice disorders among the elderly included both physical
and psychosocial aspects. However, the methodological discrepancies between the
studies, particularly in relation to sample selection and the instruments used
indicate great variability and compromise the reliability of the results.
CONCLUSION: Further prevalence studies and investigations of factors associated
with voice disorders in the elderly from an epidemiological perspective, and
which involve different cultures, should be carried out.
PMID- 29331353
TI - Mechanisms of Sex Differences in Fear and Posttraumatic Stress Disorder.
AB - Following sexual maturity, females disproportionately have higher rates of
posttraumatic stress disorder (PTSD) and experience greater symptom severity and
chronicity as compared with males. This observation has led many to examine sex
differences in PTSD risk factors. Though relatively few, these studies reveal
that the root causes of PTSD sex differences are complex, and partly represent
interactions between sex-specific nonbiological and biological risk factors,
which differentially shape PTSD vulnerability. Moreover, these studies suggest
that sex-specific PTSD vulnerability is partly regulated by sex differences in
fear systems. Fear, which represents a highly conserved adaptive response to
threatening environmental stimuli, becomes pathological in trauma- and stress
based psychiatric syndromes, such as PTSD. Over the last 30 years, considerable
progress has been made in understanding normal and pathological molecular and
behavioral fear processes in humans and animal models. Thus, fear mechanisms
represent a tractable PTSD biomarker in the study of sex differences in fear. In
this review, we discuss studies that examine nonbiological and biological sex
differences that contribute to normal and pathological fear behaviors in humans
and animal models. This, we hope, will shed greater light on the potential
mechanisms that contribute to increased PTSD vulnerability in females.
PMID- 29331354
TI - Specificity in Etiology of Subtypes of Bipolar Disorder: Evidence From a Swedish
Population-Based Family Study.
AB - BACKGROUND: Uncertainty remains whether bipolar I disorder (BDI) and bipolar II
disorder (BDII) differ etiologically. We used a population-based family sample to
examine the etiological boundaries between BDI and BDII by assessing their
familial aggregation/coaggregation and by assessing the coaggregation between
them and schizophrenia, depression, attention-deficit/hyperactivity disorder,
eating disorders, autism spectrum disorder, substance use disorders, anxiety
disorders, and personality disorders. METHODS: By linking Swedish national
registers, we established a population-based cohort (N = 15,685,511) and
identified relatives with different biological relationships. Odds ratios (ORs)
were used to measure the relative risk of BDI and BDII in relatives of
individuals diagnosed with BDI (n = 4309) and BDII (n = 4178). The heritability
for BDI and BDII and the genetic correlation across psychiatric disorders were
estimated by variance decomposition analysis. RESULTS: Compared with the general
population, the OR of BDI was 17.0 (95% confidence interval [CI] 13.1-22.0) in
first-degree relatives of BDI patients, higher than that of BDII patients (OR
9.8, 95% CI 7.7-12.5). The ORs of BDII were 13.6 (95% CI 10.2-18.2) in first
degree relatives of BDII patients and 9.8 (95% CI 7.7-12.4) in relatives of BDI
patients. The heritabilities for BDI and BDII were estimated at 57% (95% CI 32%
79%) and 46% (95% CI 21%-67%), respectively, with a genetic correlation estimated
as 0.78 (95% CI 0.36-1.00). The familial coaggregation of other psychiatric
disorders, in particular schizophrenia, showed different patterns for BDI and
BDII. CONCLUSIONS: Our results suggest a distinction between BDI and BDII in
etiology, partly due to genetic differences.
PMID- 29331355
TI - Contemporary Procedural Complications, Hospitalizations, and Emergency Visits
After Catheter Ablation for Atrial Fibrillation.
AB - Contemporary data on complications and resource utilization after atrial
fibrillation (AF) ablation are limited. We evaluated rates and risk factors for
procedural complication, rehospitalization, and emergency department visits after
AF ablation. We identified all adult patients who underwent isolated AF ablation
between 2010 and June 2014 in 2 large integrated health-care delivery systems and
evaluated rates of acute inpatient complication, 30-day, and 1-year readmission
and emergency evaluation. We used multivariable logistic regression to identify
predictors of procedural complications, 30-day readmission, or 30-day emergency
department evaluation. In 811 AF ablation patients, procedural complications
occurred in 2.5% of patients, 9.7% of patients were rehospitalized within 30
days, and 19.1% of patients had an emergency visit within 30 days. At 1 year
after AF ablation, 28.9% of patients were readmitted, with 18% of patients
readmitted for AF or atrial flutter. At 1 year, 44.5% of patients were seen in an
emergency department, with 37.1% related to AF or atrial flutter. Vascular
complications and perforation or tamponade were the most common complications,
and Hispanic ethnicity, mitral or aortic valvular disease, and diabetes mellitus
were the strongest risk factors for adverse outcomes at 30 days after AF
ablation. Contemporary rates of acute complication and 1-year readmission after
AF ablation have markedly decreased compared with previous community-based
studies.
PMID- 29331357
TI - Differentiation of Inflammatory From Fibrotic Ileal Strictures among Patients
with Crohn's Disease Based on Visual Analysis: Feasibility Study Combining
Conventional B-Mode Ultrasound, Contrast-Enhanced Ultrasound and Strain
Elastography.
AB - The aim of this pilot study was to assess prospectively the feasibility of
conventional B-mode ultrasound (US) and contrast-enhanced ultrasound (CEUS)
combined with real-time strain elastography (SE) in the differentiation of
inflammatory from fibrotic ileal strictures among patients with Crohn's disease
(CD) based on visual analysis. Twenty non-consecutive patients (15 male and 5
female; mean age +/- standard deviation, 40.2 +/- 10.22 y) with CD and stricture
of the terminal ileal loop were scanned by conventional B-mode US and CEUS and,
subsequently, by real-time SE. Two independent readers visually classified each
bowel stricture as fibrotic or inflammatory based on conventional B-mode US,
CEUS, SE, individually and then for all techniques combined. All techniques
combined had a higher (p <0.05) sensitivity (reader 1, 9/20 [45%]; reader 2, 7/20
[35%]), specificity (reader 1, 5/20 [25%]; reader 2, 8/20 [40%]) and diagnostic
accuracy (reader 1, 14/20 [70%]; reader 2, 15/20 [75%]) and higher (p <0.05) area
under the receiver operating characteristic curve (reader 1, 0.953; reader 2,
0.921) than individual techniques. Inter-reader agreement was fair for
conventional B-mode US (k = 0.46) and CEUS (k = 0.39), moderate for SE (k = 0.6)
and fair for all techniques combined (k = 0.38). Conventional B-mode US and CEUS,
in combination with SE, may improve differentiation of inflammatory from fibrotic
ileal strictures among patients with CD based on visual analysis.
PMID- 29331356
TI - Assessment of Diastolic Function Using Ultrasound Elastography.
AB - Shear wave elasticity imaging (SWEI) is a novel ultrasound elastography technique
for assessing tissue stiffness. In this study, we investigate the potential of
SWEI for providing diastolic functional assessment. In 11 isolated rabbit hearts,
pressure-volume (PV) measurements were recorded simultaneously with SWEI
recordings from the left ventricle free wall before and after induction of global
ischemia. PV-based end diastolic stiffness increased by 100% after ischemia (p
<0.05), and SWEI stiffness showed an increase of 103% (p <0.05). The relaxation
time constant (tau) before and after ischemia derived from pressure and SWEI
curves showed increases of 79% and 76%, respectively (p <0.05). A linear
regression between pressure-derived and SWEI-based (tau) showed a slope of 1.164
with R2 = 0.80, indicating the near equivalence of the two assessments. SWEI can
be used to derive (tau) values and myocardial end diastolic stiffness. In global
conditions, these measurements are consistent with PV measurements of diastolic
function.
PMID- 29331358
TI - Assessing Risk Category of Breast Cancer by Ultrasound Imaging Characteristics.
AB - The purpose of our study was to assess the potential clinical value of ultrasound
imaging in predicting risk category in patients with breast cancer. Three hundred
thirty-six patients were enrolled and divided into a high-risk group (99, 29.5%)
and mid- to low-risk group (237, 70.5%) according to the St. Gallen risk
criteria. All data were retrospectively collected to analyze correlations between
ultrasound features and risk category. The results revealed that the ultrasound
features of irregular shape (p= 0.002), vertical growth orientation (p= 0.002),
angular contour (p= 0.022) and high color Doppler flow imaging grade (p= 0.001)
tended to be present in images of the high-risk group. Therefore, tumor
ultrasound features should be recognized as an ideal option for determination of
risk category in patients with breast cancer.
PMID- 29331359
TI - Quantitative CT Evaluation of Small Pulmonary Vessels in Patients with Acute
Pulmonary Embolism.
AB - RATIONALE AND OBJECTIVES: The objective of this study was to investigate the
correlation between the computed tomography (CT) cross-sectional area (CSA) of
small pulmonary vessels and the CT obstruction index in patients with acute
pulmonary embolism (PE) and the correlation between the changes in these
measurements after anticoagulant therapy. MATERIALS AND METHODS: Fifty-two
patients with acute PE were selected for this study. We measured the CSA less
than 5 mm2 on coronal reconstructed images to obtain the percentage of the CSA
(%CSA < 5). CT angiographic index was obtained based on the Qanadli method for
the evaluation of the degree of pulmonary arterial obstruction. Spearman rank
correlation analysis was used to evaluate the relationship between the initial
and the follow-up values and changes in the %CSA < 5 and the CT obstruction
index. RESULTS: There was no significant correlation between the %CSA < 5 and CT
obstruction index on both initial (rho = -0.03, P = 0.84) and follow-up (rho =
0.03, P = 0.82) assessments. In contrast, there was a significant negative
correlation between the changes in %CSA < 5 and the CT obstruction index (rho =
0.59, P < 0.0001). CONCLUSIONS: Although the absolute %CSA < 5 and CT obstruction
index were not significantly correlated, the changes in the values of the two
parameters had a significant correlation. Changes in %CSA < 5, which can be
obtained easily, can be used as biomarker of therapeutic response in patients
with acute PE.
PMID- 29331360
TI - Fully Automated Segmentation of Polycystic Kidneys From Noncontrast Computed
Tomography: A Feasibility Study and Preliminary Results.
AB - RATIONALE AND OBJECTIVES: Total kidney volume is an important biomarker for the
evaluation of autosomal dominant polycystic kidney disease progression. In this
study, we present a novel approach for automated segmentation of polycystic
kidneys from non-contrast-enhanced computed tomography (CT) images. MATERIALS AND
METHODS: Non-contrast-enhanced CT images were acquired from 21 patients with a
diagnosis of autosomal dominant polycystic kidney disease. Kidney volumes
obtained from the fully automated method were compared to volumes obtained by
manual segmentation and evaluated using linear regression and Bland-Altman
analyses. Dice coefficient was used for performance evaluation. RESULTS: Kidney
volumes from the automated method well correlated with the ones obtained by
manual segmentation. Bland-Altman analysis showed a low percentage bias (-0.3%)
and narrow limits of agreements (11.0%). The overlap between the three
dimensional kidney surfaces obtained with our approach and by manual tracing,
expressed in terms of Dice coefficient, showed good agreement (0.91 +/- 0.02).
CONCLUSIONS: This preliminary study showed the proposed fully automated method
for renal volume assessment is feasible, exhibiting how a correct use of
biomedical image processing may allow polycystic kidney segmentation also in non
contrast-enhanced CT. Further investigation on a larger dataset is needed to
confirm the robustness of the presented approach.
PMID- 29331361
TI - Uterine Artery Embolization: An Analysis of Online Patient Information Quality
and Readability with Historical Comparison.
AB - RATIONALE AND OBJECTIVES: Investigators aimed to assess online information
describing uterine artery embolization (UAE) to examine the quality and
readability of websites patients are accessing. MATERIALS AND METHODS: A list of
applicable, commonly used searchable terms was generated, including "Uterine
Artery Embolization," "Fibroid Embolization," "Uterine Fibroid Embolization," and
"Uterine Artery Embolisation." Each possible term was assessed across the five
most-used English language search engines to determine the most commonly used
term. The most common term was then investigated across each search engine, with
the first 25 pages returned by each engine included for analysis. Duplicate
pages, nontext content such as video or audio, and pages behind paywalls were
excluded. Pages were analyzed for quality and readability using validated tools
including DISCERN score, JAMA Benchmark Criteria, HONcode Certification, Flesch
Reading Ease Score, Flesch-Kincaid Grade Level, and Gunning-Fog Index. Secondary
features such as age, rank, author, and publisher were recorded. RESULTS: The
most common applicable term was "Uterine Artery Embolization" (492,900 results).
Mean DISCERN quality of information provided by UAE websites is "fair"; however,
it has declined since comparative 2012 studies. Adherence to JAMA Benchmark
Criteria has reduced to 6.7%. UAE website readability remains more difficult than
the World Health Organization-recommended 7-8th grade reading levels. HONcode
certified websites (35.6%) demonstrated significantly higher quality than
noncertified websites. CONCLUSIONS: Quality of online UAE information remains
"fair." Adherence to JAMA benchmark criteria is poor. Readability is above
recommended 7-8th grade levels. HONcode certification was predictive of higher
website quality, a useful guide to patients requesting additional information.
PMID- 29331362
TI - Multi-model Analysis of Diffusion-weighted Imaging of Normal Testes at 3.0 T:
Preliminary Findings.
AB - RATIONALE AND OBJECTIVES: This study aimed to establish diffusion quantitative
parameters (apparent diffusion coefficient [ADC], DDC, alpha, Dapp, and Kapp) in
normal testes at 3.0 T. MATERIALS AND METHODS: Sixty-four healthy volunteers in
two age groups (A: 10-39 years; B: >= 40 years) underwent diffusion-weighted
imaging scanning at 3.0 T. ADC1000, ADC2000, ADC3000, DDC, alpha, Dapp, and Kapp
were calculated using the mono-exponential, stretched-exponential, and kurtosis
models. The correlations between parameters and the age were analyzed. The
parameters were compared between the age groups and between the right and the
left testes. RESULTS: The average ADC1000, ADC2000, ADC3000, DDC, alpha, Dapp,
and Kapp values did not significantly differ between the right and the left
testes (P > .05 for all). The following significant correlations were found:
positive correlations between age and testicular ADC1000, ADC2000, ADC3000, DDC,
and Dapp (r = 0.516, 0.518, 0.518, 0.521, and 0.516, respectively; P < .01 for
all) and negative correlations between age and testicular alpha and Kapp (r =
0.363, -0.427, respectively; P < .01 for both). Compared to group B, in group A,
ADC1000, ADC2000, ADC3000, DDC, and Dapp were significantly lower (P < .05 for
all), but alpha and Kapp were significantly higher (P < .05 for both).
CONCLUSIONS: Our study demonstrated the applicability of the testicular mono
exponential, stretched-exponential, and kurtosis models. Our results can help
establish a baseline for the normal testicular parameters in these diffusion
models. The contralateral normal testis can serve as a suitable reference for
evaluating the abnormalities of the other side. The effect of age on these
parameters requires further attention.
PMID- 29331363
TI - Breast Imaging Match Highlights the Need to Unify the Approach to Fellowship.
PMID- 29331364
TI - Picky eating, pressuring feeding, and growth in toddlers.
AB - Several common theoretical frameworks have posited causal pathways between picky
eating, pressuring feeding, and growth in early childhood. The evidence to
support these pathways is limited. This observational cohort study sought to
examine the cross-lagged associations between mother-reported pressuring feeding,
mother-reported child picky eating, and measured weight-for-length z-score (WLZ)
across child ages 21, 27, and 33 months (n = 244). Cross-lagged analysis was used
to evaluate longitudinal associations between these three constructs. The sample
was 50.5% white, 52.3% male and 37.8% of mothers had a high school education or
less. Mean WLZ was 0.52, 0.41, and 0.38 at each age, respectively. Pressuring
feeding, picky eating, and WLZ each tracked strongly from 21 to 33 months. There
were concurrent associations between pressuring feeding and picky eating.
However, there were no prospective associations between pressuring feeding and
future WLZ; WLZ and future pressuring feeding; pressuring feeding and future
picky eating; picky eating and future pressuring feeding; or picky eating and
future WLZ. Our results do not support causal relationships between picky eating,
pressuring feeding, and growth in toddlerhood. Future work that examines
alternative mechanisms shaping growth in early childhood is needed.
PMID- 29331365
TI - Assessment of test-retest reliability of a food choice task among healthy
individuals.
AB - Aberrations in eating patterns constitute a substantial public health burden.
Computer-based paradigms that measure responses to images of foods are
potentially useful tools for assessing food attitudes and characteristics of
eating behavior. In particular, food choice tasks attempt to directly probe
aspects of individuals' decisions about what to eat. In the Food Choice Task
participants rate the healthiness and tastiness of a variety of food items
presented one at a time. Next, participants choose for each food item whether
they prefer to eat the item vs. a neutrally rated reference food item. The goal
of the current study was to assess the stability and reliability of this Food
Choice Task over time and with repeated testing. Secondary analyses were
conducted using data from healthy volunteers in two separate studies that
administered the task at two time points, separated either by several days or
about a month. The overall reliability of the Food Choice Task across multiple
administrations was assessed using intra-class correlation coefficients and the
reliability of ratings of individual food items was assessed using kappa
coefficients. The results indicated that test-retest reliability of the Food
Choice Task in healthy volunteers was high at both shorter and longer test-retest
intervals. In addition, the reliability of individual food item ratings was good
for a majority of items. The proportion of healthy volunteers' high-fat food
choices did not change over time in either of the two studies. Thus, the Food
Choice Task is suitable for measuring food choices in studies with multiple
assessment points. In particular, the task may be well suited to assess
restrictive eating, a construct which it has been difficult to assess in
experimental settings.
PMID- 29331366
TI - Eating in the absence of hunger is related to loss-of-control eating, hedonic
hunger, and short-term weight gain in normal-weight women.
AB - Eating beyond physiological need contributes to obesity onset. Measuring this
behavior could help identify those at risk for weight gain. This study measured
eating in the absence of hunger (EAH) and its relationship with weight change and
self-report measures related to appetite and eating behavior. EAH was assessed in
46 lean young women (69% pre-selected for weight gain proneness) after lunch and
defined as the number of calories subsequently consumed from snacks. Participants
also completed questionnaires, and their body weights were measured regularly
over the next year. Participants consumed a mean 188 calories (+/-140) during the
EAH test. Caloric intake during the EAH test was associated with hedonic hunger
(p < .01, R2 = 0.18), loss of control eating (p < .001, R2 = 0.29), and weight
gain over two months (p < .01, R2 = 0.19), controlling for baseline body mass
index. All were large effect sizes. In contrast, EAH was unrelated to emotional
eating, disinhibition, and longer-term weight change. Amount of the test meal
eaten in a hungry state was unrelated to these variables. While EAH has mainly
been examined in children, these results expand its utility to adults. EAH seems
to reflect naturalistic eating behavior, as shown by its relationship with short
term weight gain, drive to overconsume foods, and loss of control over eating.
EAH may be a useful test to identify young adults at risk for weight gain and/or
disordered eating, and may be a target for intervention.
PMID- 29331367
TI - Molecular characterization and differential expression analysis of interleukin
1beta from Ovis aries.
AB - The interleukin-1 family is an important component of the innate immune system
and plays an important role in regulating immune responses on the invasion of
intracellular parasites in the acquired immune system. Interleukin 1beta (IL
1beta) is one of the members of the IL-1 family that predominantly activates
downstream signaling pathways to play immunological functions of stimulating T
and B lymphocyte activation and promoting the various syntheses of inflammatory
substances in conjunction with other cytokines. Here, a full-length IL-1beta cDNA
(OaIL-1beta) of sheep (Ovis aries) was cloned using rapid amplification of cDNA
ends (RACE), which consists of 1494 bp and contains a 5'-UTR region with a length
of 83 bp, a complete ORF of 801 bp in length, and a 3'-UTR region with a length
of 642 bp. Recombinant protein OaIL-1beta was expressed and purified, and the
monoclonal antibody against IL-1beta of sheep is prepared. Western blotting
results showed that the sheep IL-1beta protein was detected in the heart, liver,
lung, kidney, stomach, intestine, muscle, lymph nodes and leukocytes with the
highest expression in the muscle and the lowest expression in the lung. Different
bacteria treating sheep white blood cells induced differential expression of OaIL
1beta. Compared with the normal sheep, OaIL-1beta in the buffy coat was
differentially expressed in the Brucella melitensis-challenged group and the B.
suis S2 strain-inoculated group. However, whether IL-1beta may be considered as a
molecular biomarker for differing Brucella-infected animals from brucellosis
vaccinated animals or not need to be further studied.
PMID- 29331368
TI - In vitro and in vivo safety analysis of Enterococcus faecium 2C isolated from
human breast milk.
AB - INTRODUCTION: Safety analysis of probiotic bacteria is an obligatory
characteristic to be evaluated prior to application in food or pharmacological
products. This study was designed to evaluate in vitro and in vivo safety
parameters of Enterococcus faecium 2C strain, a probiotic candidate isolated from
human breast milk. MATERIAL AND METHODS: E.faecium 2C was studied for its
hemolytic activity and phenotypic antibiotics resistance profile. In vivo safety
of the mentioned Enterococcus strain was studied by determining acute oral
toxicity in Wistar Male rats. The animals were randomly divided into two groups
of 3 animals each. The test group animals were gavaged daily with bacterial dose
of 1 * 1011 CFU/kg of animal body weight for 21 consecutive days. The animals in
control group received normal basal diet without any supplementations.
Hematological and biochemical parameters, organ weight, body weight and common
health features of the animals were recorded. RESULTS: E.faecium 2C appeared non
hemolytic and sensitive to the majority of the tested antibiotics. The Wistar
male rats fed orally with the mentioned bacterial suspensions survived the test
period, and showed normal growth and development. No adverse effects on the
general health condition, behavior, and growth were seen in the treated animals
compared to control group. Additionally, no significant changes in the
hematological results, blood biochemistry, organ weights and histopathology of
the rats in treatment groups were observed. None of the vital organs of the
treated animals showed signs of bacteremia or infectivity. CONCLUSION: E.faecium
2C strain isolated from human breast milk might be considered safe for use in
probiotic formulations intended for man and animals.
PMID- 29331369
TI - Equisetum telmateia extracts: Chemical compositions, antioxidant activity and
antimicrobial effect on the growth of some pathogenic strain causing poisoning
and infection.
AB - The aerial parts of Equisetum telmateia have been used as a source of
biologically active compounds to treat inflammatory, diarrhea, stomach-ache,
eczema and mouth infections in traditional medicine. The aim of this work is to
evaluate the extraction yield, chemical compositions, antioxidant activity and
antimicrobial activity of E. telmateia extracts on Staphylococcus aureus,
Bacillus cereus, Escherichia coli, Salmonella typhi and Candida albicans.
Chemical compositions E. telmateia was analyzed by high performance liquid
chromatography (HPLC) using a C18 column. Analysis of E. telmateia extract by
HPLC allowed the identification of Kaempferol 3-O-(6"-O-acetylglucoside) as major
compound. The antioxidant activity of extracts was examined by measuring their
ability to sequestrate 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. The results
showed that the DPPH (IC50 = 70.83 +/- 0.2 MUg/ml) were obtained in the case of
supercritical fluid extraction (SFE) extract. MIC microdilution assay were used
to determine the antimicrobial activities. Contrary to lower extraction yield
(9.6 +/- 0.5), the SFE extract exhibited the highest antimicrobial potency with
MIC and MBC values of 32 mg/ml against S. aureus compared to the other extracts.
The results suggest that SFE method is more appropriate for extraction of E.
telmateia biologically active substances with antimicrobial and antioxidant
activity than conventional solvent extraction methods.
PMID- 29331370
TI - Preparation and evaluation of antibacterial potential of Pithecellobium dulce
root extract against Gram positive and Gram negative bacteria.
AB - In the present study hexane, benzene, ethyl acetate and ethanol extracts of
Pithecellobium dulce root were prepared using soxhlet extractor. The extracts
were evaluated for antibacterial activity against one Gram positive
(Staphylococcus aureus) and three Gram negative (Acetobacter aceti, Acetobacter
aceti, Klebsiella pneumoniae) strains. Disc diffusion method revealed promising
antibacterial activity of the extracts prepared in polar solvents (ethyl acetate
and ethanol) compared to non-polar solvents (hexane and benzene). Ethanolic root
extract was found to be most active against Acetobacter aceti, Staphylococcus
aureus, Klebsiella pneumonia and Enterobacter aerogenes bacterial strains. The
zone of inhibition of ethanolic root extract against Acetobacter aceti,
Staphylococcus aureus, Klebsiella pneumonia and Enterobacter aerogenes bacterial
strains was 15.4, 11.0, 19.0 and 13.0 mm, respectively at 100 mg concentration.
Ethyl acetate extract also exhibited good antibacterial activity against
Entrobacter aerogenes, Klebsiella pneumonia and Acetobacter aceti. The zone of
inhibition of ethyl acetate root extracts against Entrobacter aerogenes,
Acetobacter aceti and Klebsiella pneumonia was 10.5, 18.0 and 10.0 mm,
respectively. The benzene extract showed some activity against Acetobacter aceti
with the zone of inhibition 10.0 mm. The antibacterial activity of Pithecellobium
dulce root hexane extract was found to be negligible against all the four tested
strains of bacteria. These findings suggest that ethanolic and ethyl acetate root
extracts of Pithecellobium dulce has potential as effective anti-bacterial agent.
PMID- 29331372
TI - Cancer care delivery research in gynecologic oncology.
PMID- 29331371
TI - Birth weight and the risk of histological subtypes of ovarian and endometrial
cancers: Results from the Copenhagen School Health Records Register.
AB - BACKGROUND: Studies of birth weight associations with ovarian and endometrial
cancer risks are limited with inconsistent results, and none has evaluated
associations by histologic subtype. We utilized prospectively collected birth
weight information to investigate the association with risk of ovarian and
endometrial cancers overall and by histologic subtype. METHODS: 162,559 girls,
born from 1930 to 1989, from the Copenhagen School Health Records Register
(CSHRR) were followed prospectively via linkage with the Danish health registers.
Ovarian (n=666) and endometrial (n=694) cancers were identified from 1978 to
2014. Cox regression was used to estimate hazard ratios (HR) and 95% confidence
intervals (CI). RESULTS: Women with lower (2.0-3.25 vs. 3.26-3.75kg) and higher
(3.75-5.5 vs. 3.26-3.75kg) birth weights had increased risks of ovarian cancer
overall [HR (95% CI): 1.27 (1.06-1.52); 1.51 (1.21-1.87), respectively] and
serous ovarian cancers [1.54 (1.19-1.98); 1.98 (1.47-2.67), respectively]. A
decreased risk of Type II endometrial tumors was suggested per kilogram increase
in birth weight [HR (95% CI): 0.63 (0.40-1.00)]. CONCLUSIONS: Our results suggest
that both lower and higher birth weights were associated with increased ovarian
cancer risk and associations were particularly strong for serous ovarian cancer,
the most common subtype. Birth weight was not associated with most types of
endometrial cancer.
PMID- 29331374
TI - Alternative pathway of H2S and polysulfides production from sulfurated catalytic
cysteine of reaction intermediates of 3-mercaptopyruvate sulfurtransferase.
AB - It has been known that hydrogen sulfide and/or polysulfides are produced from a
(poly)sulfurated sulfur-acceptor substrate of 3-mercaptopyruvate
sulfurtransferase (MST) via thioredoxin (Trx) reduction in vitro. In this study,
we used thiosulfate as the donor substrate and the catalytic reaction was
terminated on the formation of a persulfide or polysulfides. We can present
alternative pathway of production of hydrogen sulfide and/or polysulfides from
(poly)sulfurated catalytic-site cysteine of reaction intermediates of MST via Trx
reduction. Matrix-assisted laser desorption ionization tandem time-of-flight mass
spectrometric analysis revealed that after prolonged incubation of MST with
thiosulfate, a trisulfide adduct becomes predominant at the sulfurated catalytic
site cysteine. When these adducts were reduced by Trx with reducing system
(MST:Escherichia coli Trx:E. coli Trx reductase:NADPH = 1:5:0.02:12.5 molar
ratio), liquid chromatography with tandem mass spectrometric analysis for
monobromobimane-derivatized H2Sn revealed that H2S2 first appeared, and then H2S
and H2S3 did later. The results were confirmed by high-performance liquid
chromatography-fluorescence analysis.
PMID- 29331373
TI - Establishment and characterization of five immortalized human scalp dermal
papilla cell lines.
AB - Dermal papilla (DP) regulates the growth and cycling of hair follicles. Cultured
DP cells are useful for the study of their role in relation to hair growth and
regeneration. However, cultivation of human DP cells is tedious and difficult. In
addition, cultured DP cells possess a relatively short replicative life span,
requiring immortalized human DP cell lines. We previously established an
immortalized human DP cell line, SV40T-hTERT-DPC, by introducing human telomerase
reverse transcriptase (hTERT) gene into the transformed cell line, SV40T-DPC. In
this study, we co-transfected the simian virus 40 large T antigen (SV40T-Ag) and
hTERT into DP cells from scalp hair follicles from a male with androgenetic
alopecia and established five immortalized DP cell lines and named KNU-101, KNU
102, KNU-103, KNU-201 and KNU-202. We then evaluated tumorigenicity, expression
of DP markers, responses to androgen, Wnt3a and BMP4, and expression of DP
signature genes. These cell lines displayed early passage morphology and
maintained responses to androgen, Wnt and BMP. Furthermore, these cell lines
expressed DP markers and DP signature genes. KNU cell lines established in this
study are potentially useful sources for hair research.
PMID- 29331375
TI - Xanthomonas TAL effectors hijack host basal transcription factor IIA alpha and
gamma subunits for invasion.
AB - The Xanthomonas genus includes Gram-negative plant-pathogenic bacteria, which
infect a broad range of crops and wild plant species, cause symptoms with leaf
blights, streaks, spots, stripes, necrosis, wilt, cankers and gummosis on leaves,
stems and fruits in a wide variety of plants via injecting their effector
proteins into the host cell during infection. Among these virulent effectors,
transcription activator-like effectors (TALEs) interact with the gamma subunit of
host transcription factor IIA (TFIIAgamma) to activate the transcription of host
disease susceptibility genes. Functional TFIIA is a ternary complex comprising
alpha, beta and gamma subunits. However, whether TALEs recruit TFIIAalpha,
TFIIAbeta, or both remains unknown. The underlying molecular mechanisms by which
TALEs mediate host susceptibility gene activation require full elucidation. Here,
we show that TALEs interact with the alpha+gamma binary subcomplex but not the
alpha+beta+gamma ternary complex of rice TFIIA (holo-OsTFIIA). The transcription
factor binding (TFB) regions of TALEs, which are highly conserved in Xanthomonas
species, have a dominant role in these interactions. Furthermore, the interaction
between TALEs and the alpha+gamma complex exhibits robust DNA binding activity in
vitro. These results collectively demonstrate that TALE-carrying pathogens hijack
the host basal transcription factors TFIIAalpha and TFIIAgamma, but not
TFIIAbeta, to enhance host susceptibility during pathogen infection. The
uncovered mechanism widens new insights on host-microbe interaction and provide
an applicable strategy to breed high-resistance crop varieties.
PMID- 29331376
TI - MicroRNA-425 facilitates pathogenic Th17 cell differentiation by targeting
forkhead box O1 (Foxo1) and is associated with inflammatory bowel disease.
AB - Inflammatory bowel disease (IBD) is a chronic autoimmune disease, and its
pathogenesis remains mostly unknown. MicroRNAs (miRs) has drawn much attention as
a crucial regulator of autoimmune diseases. In this study, we demonstrated, for
the first time, that miR-425 was significantly up-regulated in peripheral blood
mononuclear cells (PBMC) and mucosa of patients with IBD. In note, T helper (Th)
17 cells were found to be the major source of miR-425 expression. Using gain-of
function approaches, we demonstrated that miR-425 could facilitate the
differentiation of CD4+ T cells into Th17 lineage. In addition, forkhead box O1
(Foxo1) was identified as a novel target gene of miR-425, which was able to
inhibit Th17 cell differentiation, and it was observed to be markedly decreased
in PBMC and mucosa of patients with IBD. Notably, in vivo inhibition of miR-425
significantly alleviated the disease severity of TNBS-induced colitis in mice,
with down-regulated levels of IL-17A. Our data reveal a novel mechanism in which
the elevated miR-425 in IBD mediates pathogenic Th17 cell generation through down
regulation of Foxo1. In vivo blockade of miR-425 may serve as a novel therapeutic
approach in the treatment of IBD.
PMID- 29331377
TI - beta-cellulin promotes the proliferation of corneal epithelial stem cells through
the phosphorylation of erk1/2.
AB - The proliferation of corneal epithelial stem cells (CESCs) is a very important
process in the recovery of corneal wounds. Recent studies have shown that beta
cellulin (BC) is effective in the repair of other tissues. However, its mechanism
of action in corneal wound healing is not yet clear. The purpose of this study
was to investigate how BC accelerates wound healing of the cornea. Here, we
confirmed that the proliferation of CESCs was induced at a specific concentration
(0.2, 2 and 20 ng/mL) by treatment with BC. Markers associated with proliferation
activity (DeltaNp63, bmi-1, abcg2) were also upregulated. In vivo experiments
showed that the corneal wound healing rate was increased in mice. We found that
BC stimulates the phosphorylation of the erk1/2 signaling pathway, which is
triggered during the recovery of mouse corneal wounds. However, the inhibition of
erk1/2 phosphorylation delayed the recovery of mouse corneal wounds in an organ
culture assay. According to these results, BC may be a potential treatment factor
for corneal wound healing.
PMID- 29331379
TI - Effect of histidine on sorafenib-induced vascular damage: Analysis using novel
medaka fish model.
AB - BACKGROUND: Sorafenib (SFN) is an anti-angiogenic chemotherapeutic that prolongs
survival of patients with hepatocellular carcinoma (HCC); its side effects,
including vascular damages such as hand-foot syndrome (HFS), are a major cause of
therapy discontinuation. We previously reported that maintenance of peripheral
blood flow by intake of dried bonito broth (DBB) significantly prevented HFS and
prolonged the administration period. The amino acids contained in DBB probably
contribute to its effects, but the mechanism has not been clarified. We
hypothesized that histidine, the largest component among the amino acids
contained in DBB, has effects on SFN-induced vascular damage, and evaluated this
possibility using a novel medaka fish model. METHODS: The fli::GFP transgenic
medaka fish model has a fluorescently visible systemic vasculature. We fed the
fish with SFN with and without histidine to compare blood flow and vascular
structure among the differently fed models. The vascular cross-sectional area of
each fish was measured to determine vascular diameter changes. RESULTS: Our
results demonstrated that SFN-fed medaka developed a narrower vascular diameter.
In addition, this narrowing was counteracted by addition of histidine to the
medaka diet. We observed no positive effect of histidine on regeneration of cut
vessels or on cell growth of endothelial cells and HCC cell lines. CONCLUSION: We
proved the efficacy of the medaka model to assess vascular changes after
administration of specific chemicals. And our results suggest that SFN causes
vascular damage by narrowing peripheral vessel diameter, and that histidine
effectively counteracts these changes to maintain blood flow.
PMID- 29331380
TI - Eicosapentaenoic acid inhibits oxidation of high density lipoprotein particles in
a manner distinct from docosahexaenoic acid.
AB - The omega-3 fatty acid eicosapentaenoic acid (EPA) reduces oxidation of ApoB
containing particles in vitro and in patients with hypertriglyceridemia. EPA may
produce these effects through a potent antioxidant mechanism, which may
facilitate LDL clearance and slow plaque progression. We hypothesize that EPA
antioxidant effects may extend to ApoA-containing particles like HDL, potentially
preserving certain atheroprotective functions. HDL was isolated from human plasma
and incubated at 37 degrees C in the absence (vehicle) or presence of EPA and/or
DHA; 5.0 or 10.0 MUM each. Samples were then subjected to copper-induced
oxidation (10 MUM). HDL oxidation was inhibited similarly by EPA and DHA up to 1
h. EPA (10 MUM) maintained significant HDL oxidation inhibition of 89% (0.622 +/-
0.066 MUM MDA; p < .001) at 4 h, with continued inhibition of 64% at 14 h, vs.
vehicle (5.65 +/- 0.06 to 2.01 +/- 0.10 MUM MDA; p < .001). Conversely, DHA (10
MUM) antioxidant benefit was lost by 4 h. At a lower concentration (5 MUM), EPA
antioxidant activity remained at 81% (5.53 +/- 0.15 to 1.03 +/- 0.10 MUM MDA; p <
.001) at 6 h, while DHA lost all antioxidant activity by 4 h. The antioxidant
activity of EPA was preserved when combined with an equimolar concentration of
DHA (5 MUM each). EPA pretreatment prevented HDL oxidation in a dose-dependent
manner that was preserved over time. These results suggest unique lipophilic and
electron stabilization properties for EPA as compared to DHA with respect to
inhibition of HDL oxidation. These antioxidant effects of EPA may enhance certain
atheroprotective functions for HDL.
PMID- 29331378
TI - Loss of zebrafish Smyd1a interferes with myofibrillar integrity without
triggering the misfolded myosin response.
AB - Sarcomeric protein turnover needs to be tightly balanced to assure proper
assembly and renewal of sarcomeric units within muscle tissues. The mechanisms
regulating these fundamental processes are only poorly understood, but of great
clinical importance since many cardiac and skeletal muscle diseases are
associated with defective sarcomeric organization. The SET- and MYND domain
containing protein 1b (Smyd1b) is known to play a crucial role in
myofibrillogenesis by functionally interacting with the myosin chaperones Unc45b
and Hsp90alpha1. In zebrafish, Smyd1b, Unc45b and Hsp90alpha1 are part of the
misfolded myosin response (MMR), a regulatory transcriptional response that is
activated by disturbed myosin homeostasis. Genome duplication in zebrafish led to
a second smyd1 gene, termed smyd1a. Morpholino- and CRISPR/Cas9-mediated
knockdown of smyd1a led to significant perturbations in sarcomere structure
resulting in decreased cardiac as well as skeletal muscle function. Similar to
Smyd1b, we found Smyd1a to localize to the sarcomeric M-band in skeletal and
cardiac muscles. Overexpression of smyd1a efficiently compensated for the loss of
Smyd1b in flatline (fla) mutant zebrafish embryos, rescued the myopathic
phenotype and suppressed the MMR in Smyd1b-deficient embryos, suggesting
overlapping functions of both Smyd1 paralogs. Interestingly, Smyd1a is not
transcriptionally activated in Smyd1b-deficient fla mutants, demonstrating lack
of genetic compensation despite the functional redundancy of both zebrafish Smyd1
paralogs.
PMID- 29331381
TI - Clinical Outcomes of First-line Abiraterone Acetate or Enzalutamide for
Metastatic Castration-resistant Prostate Cancer After Androgen Deprivation
Therapy + Docetaxel or ADT Alone for Metastatic Hormone-sensitive Prostate
Cancer.
AB - BACKGROUND: The CHAARTED (ChemoHormonal Therapy Versus Androgen Ablation
Randomized Trial for Extensive Disease in Prostate Cancer) and STAMPEDE (Systemic
Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy)
trials showed that the addition of docetaxel (D) to androgen deprivation therapy
(ADT) prolonged longevity of men with metastatic hormone-sensitive prostate
cancer (mHSPC). However, the impact of upfront D on subsequent therapies is still
unexplored. As abiraterone acetate (AA) and enzalutamide (E) are the most
commonly used first-line treatment for metastatic castration-resistant prostate
cancer (mCRPC), we aimed to assess whether they maintained their efficacy after
ADT+D versus ADT alone. PATIENTS AND METHODS: A cohort of patients with mCRPC
treated between 2014 and 2017 with first-line AA or E for mCRPC was identified
from 3 hospitals' institutional review board-approved databases. Patients were
classified by use of D for mHSPC. This time frame was chosen as ADT+D became a
valid therapeutic option for mHSPC in 2014, and it inherently entailed a short
follow-up time on AA/E. The endpoints included overall survival from ADT start,
overall survival from AA/E start, and time to AA/E start from ADT start.
Differences between groups were assessed using the log-rank test. RESULTS: Of the
102 patients with mCRPC identified, 50 (49%) had previously received ADT alone,
while 52 (51%) had ADT+D. No statistically significant difference in any of the
evaluated outcomes was observed between the 2 cohorts. Yet, deaths in the ADT+D
group were 12 versus 21 in the ADT alone, after a median follow-up of 24.4 and
29.8 months, respectively. CONCLUSION: In a cohort of ADT/ADT+D-treated patients
with mCRPC with short times to first-line AA/E and follow-up, the efficacy of
AA/E is similar regardless of previous use of D.
PMID- 29331382
TI - Improved Human Pharmacokinetic Prediction of Hepatically Metabolized Drugs With
Species-Specific Systemic Clearance.
AB - Accurate prediction of human pharmacokinetics (PK) is important for the choice of
promising compounds in humans. As the predictability of human PK by an empirical
approach is low for drugs with species-specific PK, the utility of a
physiologically based pharmacokinetic (PBPK) model was verified using 16
hepatically metabolized reference drugs. After the prediction method for total
clearance (CLtot) and distribution volume at steady state (Vdss) in the
conventional PBPK model had been optimized, plasma concentrations following a
single oral administration of each reference drug to healthy volunteers were
simulated, and the prediction accuracy for human PK was compared between
empirical approaches and the optimized PBPK model. In the drugs with low species
specific CLtot, there was little difference in predictability for maximum
concentration (Cmax), time to maximum plasma concentration (Tmax), and area under
the curve (AUC) (absolute average fold error: 1.3-2.4). In contrast, the
optimized PBPK model predicted Cmax and AUC of the drugs with high species
specific CLtot with lower absolute average fold error (Cmax and AUC: 2.8 and 3.2,
respectively) than those of the empirical approach (Cmax and AUC: 2.6-4.9 and 3.9
10.7, respectively). Therefore, the optimized PBPK model is useful for human PK
prediction of drugs with species-specific CLtot.
PMID- 29331383
TI - Population Pharmacokinetics of High-Dose Methotrexate in Patients With Primary
Central Nervous System Lymphoma.
AB - The intra- and inter-individual variances of methotrexate (MTX) pharmacokinetics
are extremely large, and the pharmacokinetic property of MTX in patients with
primary central nervous system lymphoma (PCNSL) is unestablished. A total of 701
MTX plasma concentrations from 98 patients with PCNSL under high-dose MTX therapy
were used to develop the population pharmacokinetic (popPK) model of MTX by using
the nonlinear mixed-effects modeling method. A 2-compartment model was employed
to describe the pharmacokinetic property of MTX. In the final popPK model,
inclusion of serum creatinine and body surface area significantly reduced
objective function value for clearance over the base model (p <0.001), and
inclusion of age significantly reduced objective function value for distribution
volume of central compartment (Vc) over the base model (p <0.001). In the final
popPK model, the inter-individual clearance = 6.67 * (SCR/68.1)-0.48 *
(BSA/1.75)1.17; Vc = 24.46 * (age/57.16)0.81. The precision of all parameters was
acceptable (relative standard error <28.61%). Bootstrap and visual predictive
check results indicated that the final popPK model was stable with acceptable
predictive ability. The popPK model may be useful for personalized medication in
PCNSL patients under high-dose MTX therapy. Further studies are warranted to
confirm the results.
PMID- 29331384
TI - Evaluative feedback delivery and the factors that affect success.
AB - This study examines the factors that can affect the credibility, influence, and
utility of evaluative feedback. These factors include the delivery strategy,
accuracy, and type (positive/negative) of feedback provided. In this study over
500 participants were asked to complete a task, and were then randomly assigned
to different conditions with varied feedback delivery methods, feedback accuracy,
and types of feedback (positive/negative). Then they were asked questions about
the feedback's credibility, influence, and utility.
PMID- 29331387
TI - Tumor associated macrophages and angiogenesis dual-recognizable nanoparticles for
enhanced cancer chemotherapy.
AB - Tumor-associated macrophages (TAMs) and angiogenesis are increasingly considered
as the pivotal factors that affect tumor progress. Herein, we developed the
paclitaxel (PTX)-loaded nanoparticles (NP/PTX) and decorated it with an
innovative peptide YI (YINP/PTX) for simultaneously targeting delivery of drug to
TAMs and angiogenesis. We demonstrated that the modification of YI peptide
significantly enhanced the internalization of nanoparticles by cells and
accumulation of nanoparticles in tumor tissues, but down regulated the
distribution of them in normal tissues especially the liver. We also made a
confirmation that the YI peptide decorated nanoparticles had an excellent co
localization with TAMs and angiogenesis in vivo. Finally, in the HT-26 colorectal
tumor-bearing mice, a pharmacodynamic evaluation was performed and results showed
that the YINP/PTX was more effective than other PTX formulations in anti-tumor
growth. These results together suggested that the prepared nanoparticles are
promising in targeting delivery of chemotherapeutics to tumor microenvironment
for enhancing tumor therapy effect.
PMID- 29331385
TI - Guidelines of care for the management of basal cell carcinoma.
AB - Basal cell carcinoma (BCC) is the most common form of human cancer, with a
continually increasing annual incidence in the United States. When diagnosed
early, the majority of BCCs are readily treated with office-based therapy, which
is highly curative. In these evidence-based guidelines of care, we provide
recommendations for the management of patients with BCC, as well as an in-depth
review of the best available literature in support of these recommendations. We
discuss biopsy techniques for a clinically suspicious lesion and offer
recommendations for the histopathologic interpretation of BCC. In the absence of
a formal staging system, the best available stratification based on risk for
recurrence is reviewed. With regard to treatment, we provide recommendations on
treatment modalities along a broad therapeutic spectrum, ranging from topical
agents and superficially destructive modalities to surgical techniques and
systemic therapy. Finally, we review the available literature and provide
recommendations on prevention and the most appropriate follow-up for patients in
whom BCC has been diagnosed.
PMID- 29331386
TI - Guidelines of care for the management of cutaneous squamous cell carcinoma.
AB - Cutaneous squamous cell carcinoma (cSCC) is the second most common form of human
cancer and has an increasing annual incidence. Although most cSCC is cured with
office-based therapy, advanced cSCC poses a significant risk for morbidity,
impact on quality of life, and death. This document provides evidence-based
recommendations for the management of patients with cSCC. Topics addressed
include biopsy techniques and histopathologic assessment, tumor staging, surgical
and nonsurgical management, follow-up and prevention of recurrence, and
management of advanced disease. The primary focus of these recommendations is on
evaluation and management of primary cSCC and localized disease, but where
relevant, applicability to recurrent cSCC is noted, as is general information on
the management of patients with metastatic disease.
PMID- 29331388
TI - E4BP4 inhibits AngII-induced apoptosis in H9c2 cardiomyoblasts by activating the
PI3K-Akt pathway and promoting calcium uptake.
AB - The bZIP transcription factor E4BP4 is a survival factor that is known to be
elevated in diseased heart and promote cell survival. In this study the role of
E4BP4 on angiotensin-II (AngII)-induced apoptosis has been examined in in vitro
cell model. H9c2 cardiomyoblast cells that overexpressed E4BP4 were exposed to
AngII to observe the cardio-protective effects of E4BP4 on hypertension related
apoptosis. The results from TUNEL assays revealed that E4BP4 significantly
attenuated AngII-induced apoptosis. Further analysis by Western blot and RT-PCR
showed that E4BP4 inhibited AngII-induced IGF-II mRNA expression and cleavage of
caspase-3 through the PI3K-Akt pathway. In addition, E4BP4 enhanced calcium
reuptake into the sacroplasmic reticulum by down-regulating PP2A and by up
regulating the phosphorylation of PKA and PLB proteins. Our findings indicate
that E4BP4 functions as a survival factor in cardiomyoblasts by inhibiting IGF-II
transcription and by regulating calcium cycling.
PMID- 29331389
TI - Capn4 promotes colorectal cancer cell proliferation by increasing MAPK7 through
activation of the Wnt/beta-Catenin pathway.
AB - Increasing evidence has suggested that Capn4 is upregulated and functions as a
potential tumor promoter in several human cancer types. However, the potential
biological roles and regulatory mechanisms of Capn4 in colorectal cancer (CRC)
remains unclear. Here, we found that Capn4 expression was elevated in CRC tissues
than adjacent noncancerous tissues. Additionally, we also found that
overexpression of Capn4 is significantly correlated with tumor progression and
poor survival in CRC patients. Furthermore, our experimental data revealed that
increased expression of Capn4 was observed in CRC cell lines and ectopic
expression of Capn4 significantly enhanced in vitro cell proliferation, whereas
knockdown of Capn4 suppressed CRC cells growth in vitro and in vivo. Moreover,
our results indicate that Capn4 promotes cell proliferation by increasing MAPK7
expression, which has been reported to control the proliferation of many cancers.
Mechanistically, Capn4 upregulates MAPK7 expression through activation of the
Wnt/beta-Catenin pathway in CRC cells. Therefore, we identified a tumorigenic
role of Capn4 in CRC and suggested a potential therapeutic target for CRC
patients.
PMID- 29331390
TI - The TET2/E-cadherin/beta-catenin regulatory loop confers growth and invasion in
hepatocellular carcinoma cells.
AB - The poor outcome of hepatocellular carcinoma (HCC) is mainly due to the
development of fast growth, invasion and metastasis. The role of TET2 has been
implicated in some cancer types, but its role and mechanisms in HCC remains
elusive. In this study, our findings indicated that TET2 expression frequently
increased in HCC and that TET2 expressional upregulation correlated with HCC
progression. TET2 knockdown inhibited HCC cells proliferation in vitro and growth
in vivo, and inhibited the invasion potential of HCC cells. Mechanically, TET2
knockdown upregulated E-cadherin expression and then attenuated beta-catenin
transactivation in HCC cells. TET2 repressed E-cadherin expression via recruited
HDAC1 to E-cadherin promoter to reduce the H3K9Ac and H4K16Ac levels. Moreover,
beta-catenin signaling transcriptionally regulated TET2 expression to form a
positive feedback in HCC cells. These findings indicate that the dysregulation of
TET2/E-cadherin/beta-catenin regulatory loop is a critical oncogenic event in HCC
progression.
PMID- 29331391
TI - microRNA-mediated regulation of splicing factors SRSF1, SRSF2 and hnRNP A1 in
context of their alternatively spliced 3'UTRs.
AB - SRSF1, SRSF2 and hnRNP A1 are splicing factors that regulate the expression of
oncogenes and tumor suppressors. SRSF1 and SRSF2 contribute to the carcinogenesis
in the kidney. Despite their importance, the mechanisms regulating their
expression in cancer are not entirely understood. Here, we investigated the
microRNA-mediated regulation of SRSF1, SRSF2 and hnRNP A1 in renal cancer. The
expression of microRNAs predicted to target SRSF1, SRSF2 and hnRNP A1 was
disturbed in renal tumors compared with controls. Using qPCR, Western blot/ICC
and luciferase reporter system assays we identified microRNAs that contribute to
the regulation of expression of SRSF1 (miR-10b-5p, miR-203a-3p), SRSF2 (miR-183
5p, miR-200c-3p), and hnRNP A1 (miR-135a-5p, miR-149-5p). Silencing of SRSF1 and
SRSF2 enhanced the expression of their targeting microRNAs. miR-183-5p and miR
200c-3p affected the expression of SRSF2-target genes, TNFRSF1B, TNFRSF9, CRADD
and TP53. 3'UTR variants of SRSF1 and SRSF2 differed by the presence of miRNA
binding sites. In conclusion, we identified a group of microRNAs that contribute
to the regulation of expression of SRSF1, SRSF2 and hnRNP A1. The microRNAs
targeting SRSF1 and SRSF2 are involved in a regulatory feedback loop. microRNAs
miR-183-5p and miR-200c-3p that target SRSF2, affect the expression of genes
involved in apoptotic regulation.
PMID- 29331392
TI - What gynaecologists need to master: Consensus on medical expertise outcome of pan
European postgraduate training in obstetrics and gynecology.
PMID- 29331395
TI - Tyrosine hydroxylase as a sentinel for central and peripheral tissue responses in
Parkinson's progression: Evidence from clinical studies and neurotoxin models.
AB - Parkinson's disease (PD) is a common neurodegenerative disease worldwide. While
the typical motor symptoms of PD are well known, the lesser known non-motor
symptoms can also greatly impact the patient's quality of life. These symptoms
often appear before motor impairment, therefore identifying biomarkers that may
predict PD risk or pathology has been a major and challenging endeavour. Given
that the loss of dopamine, and its rate-limiting enzyme tyrosine hydroxylase (TH)
occurs in PD, the expression and accompanying post-translational changes in TH
during PD progression could yield insight into the disruption of cellular
signalling occurring in the CNS, and also in peripheral tissues wherein
catecholamine function plays a role. Furthermore, changes in expression and
phosphorylation of TH in the brain and periphery can potentially reveal how TH
stability and function are compromised in PD. As such, these changes can reveal
how catecholamine synthesis capacity is gradually compromised and how changes in
cellular signalling may govern the functional status of remaining
catecholaminergic neurons. This review summarises the findings of clinical PD and
neurotoxin models of PD that assessed TH expression or phosphorylation in
catecholaminergic pathways in the brain and relevant peripheral tissues. We
propose that establishing similar changes in TH expression and function in the
CNS and periphery of established neurotoxin models can be a potential reference
for comparison to changes in TH in human peripheral tissues. These changes in TH
expression and phosphorylation may have predictive validity to estimate risk of
PD progression before motor impairment is evident.
PMID- 29331393
TI - Oral health considerations for pediatric patients with sickle cell disease.
PMID- 29331396
TI - Autophagy in ischemic stroke.
AB - Autophagy is a self-eating cellular catabolic pathway, through which long-lived
proteins, damaged organelles and misfolded proteins are degraded and recycled for
the maintenance of cellular homeostasis and normal cellular functions. Autophagy
plays an important homeostatic role in the regulation of cell survival.
Accumulating evidence shows that autophagy is activated in various cell types in
the brain such as neurons, glia cells, and brain microvascular cells upon
ischemic stroke. However, the exact role and molecular mechanisms of autophagy
process that is implicated in ischemic stroke have yet to be elucidated. This
review aims to provide a comprehensive view of the regulation of autophagy in
neurons, glia cells, and brain microvascular cells in response to ischemia
stress. We also review the recent advance on the understanding of the involvement
of autophagy in the pathological process during cerebral ischemic
preconditioning, perconditioning and postconditioning. We propose a crosstalk
between autophagy, necroptosis, and apoptosis that contribute to ischemic stroke.
In addition, we discuss the interactions between autophagy and oxidative stress,
mitochondrial dysfunction and endoplasmic reticulum stress.
PMID- 29331397
TI - Persistent hyperparathyroidism as a risk factor for long-term graft failure: the
need to discuss indication for parathyroidectomy.
AB - BACKGROUND: Although a successful kidney transplant (KTx) improves most of the
mineral and bone disorders (MBD) produced by chronic kidney disease (CKD),
hyperparathyroidism may persist (pHPT). Current guidelines recommend
parathyroidectomy if serum parathormone is persistently elevated 1 year after
KTx, because pHPT has been recently associated with poor graft outcomes. However,
whether patients with pHPT and adequate renal function are at risk for long-term
graft failure is unknown. METHODS: Longitudinal follow-up of 911 adults submitted
to KTx between January 2005 and December 2014, with estimated glomerular
filtration rate (eGFR) >= 30 mL/min 1 year after surgery. Clinical and laboratory
data were collected from electronic database. Graft failure was defined as return
to dialysis. RESULTS: Overall, 62% of the patients were classified as having pHPT
1 year after KTx. After a mean follow-up time of 47 months, there were 59 graft
failures (49 in pHPT and 10 in non-pHPT group, P = .003). At last follow-up,
death-censored graft survival was lower in the pHPT group (P = .009), even after
adjustment for age at KTx, donor age, donor type, acute rejection,
parathyroidectomy, and eGFR at 1 year after transplantation (odds ratio [OR]
1.99; 1.004-3.971; P = .049). A PTH of 150 pg/mL at 6 months was the best cutoff
to predict pHPT at 1 year (specificity = 92.1%). CONCLUSION: Having pHPT after a
successful KTx increases the long-term risk of death-censored graft failure. This
result highlights the need for better recognition and management of CKD-MBD
before and during the first year after KTx, and opens a discussion on the more
appropriate timing to perform parathyroidectomy.
PMID- 29331399
TI - Discussion.
PMID- 29331398
TI - Critical differences between elective and emergency surgery: identifying domains
for quality improvement in emergency general surgery.
AB - OBJECTIVE: The objective of our study was to characterize providers' impressions
of factors contributing to disproportionate rates of morbidity and mortality in
emergency general surgery to identify targets for care quality improvement.
BACKGROUND: Emergency general surgery is characterized by a high-cost burden and
disproportionate morbidity and mortality. Factors contributing to these observed
disparities are not comprehensively understood and targets for quality
improvement have not been formally developed. METHODS: Using a grounded theory
approach, emergency general surgery providers were recruited through purposive
criterion-based sampling to participate in semi-structured interviews and focus
groups. Participants were asked to identify contributors to emergency general
surgery outcomes, to define effective care for EGS patients, and to describe
operating room team structure. Interviews were performed to thematic saturation.
Transcripts were iteratively coded and analyzed within and across cases to
identify emergent themes. Member checking was performed to establish credibility
of the findings. RESULTS: A total of 40 participants from 5 academic hospitals
participated in either individual interviews (n = 25 [9 anesthesia, 12 surgery, 4
nursing]) or focus groups (n = 2 [15 nursing]). Emergency general surgery was
characterized by an exceptionally high level of variability, which can be
subcategorized as patient-variability (acute physiology and comorbidities) and
system-variability (operating room resources and workforce). Multidisciplinary
communication is identified as a modifier to variability in emergency general
surgery; however, nursing is often left out of early communication exchanges.
CONCLUSION: Critical variability in emergency general surgery may impact
outcomes. Patient-variability and system-variability, with focus on
multidisciplinary communication, represent potential domains for quality
improvement in this field.
PMID- 29331400
TI - Locally advanced pancreas cancer: Staging and goals of therapy.
AB - BACKGROUND: Patients with locally advanced pancreatic cancer have historically
been considered inoperable. The purpose of this report was to determine
resectability rates for patients with locally advanced pancreatic cancer based on
our recently described definitions of type A and type B locally advanced
pancreatic cancer. METHODS: An institutional prospective pancreas cancer database
was queried for consecutive patients with locally advanced pancreatic cancer
treated between January 2009 and June 2017. All pretreatment imaging was re
reviewed and patients were categorized as locally advanced pancreatic cancer type
A or type B. Demographics, induction therapy, resection type, and outcomes were
reviewed. RESULTS: We identified 108 consecutive patients; 12 were excluded from
analysis due to the absence of available pretreatment imaging or they had not yet
completed all intended neoadjuvant therapy. Of the remaining 96 patients (45 type
A, 51 type B), disease progression occurred in 19 (20%) during induction therapy
and 30 (31%) were deemed inoperable at final preoperative restaging. Therefore,
47 (49%) of 96 patients were taken to surgery and 40 (42%) underwent successful
resection (28 [62%] of 45 type A and 12 [24%] of 51 type B); an RO resection was
achieved in 32 (80%). Metastatic disease was found intraoperatively (6 at
laparoscopy, 1 at laparotomy) in 7 (15%) of 47 patients. There were no
mortalities; 6 (15%) patients experienced major postoperative complications.
Resected patients had a median overall survival of 38.9 months. CONCLUSION:
Locally advanced pancreatic cancer can be dichotomized into type A and B with
distinctly different probabilities of completing all therapy to include surgery;
thereby allowing goals of therapy to be established at the time of diagnosis.
Multimodality therapy that includes surgery can be accomplished in selected
patients with locally advanced pancreatic cancer and is associated with a median
overall survival that approximates earlier stages of disease. (Surgery
2017;160:XXX-XXX.).
PMID- 29331401
TI - Preoperative dipstick albuminuria and other urine abnormalities predict acute
kidney injury and patient outcomes.
AB - BACKGROUND: It is unclear whether pathologic findings on preoperative urinalysis
are associated with the risk of postoperative acute kidney injury (AKI).
Therefore, we performed a retrospective review to investigate this association.
METHODS: We assessed the clinical significance of preoperative dipstick
urinalysis in a 10-year surgery cohort from a tertiary hospital in Korea.
Patients without available information on perioperative serum creatinine levels
or kidney injury prior to surgery were excluded. Preoperative dipstick urinalysis
parameters, including albuminuria, hematuria, pyuria, and others were studied.
The primary outcome was postoperative acute kidney injury. Secondary outcomes
were postoperative 1-year mortality and progression of poor kidney function
parameters. RESULTS: We enrolled 40,090 patients. The presence of dipstick
albuminuria was associated with an increased risk of postoperative AKI (adjusted
odds ratio 1.47 [1.29-1.66], P < .001), and the association showed a dose
response relationship. High specific gravity was significantly associated with
increased risk of AKI (adjusted odds ratio 1.30 [1.04-1.63], P = .02).
Furthermore, in patients with postoperative AKI, those with baseline albuminuria
had a worse prognosis with regard to 1-year mortality (adjusted hazard ratio 2.81
[1.56-5.09], P < .001) and persistent renal function impairment (adjusted odds
ratio 2.07 [1.21-3.46], P = .007), independent of estimated glomerular filtration
rate values. Patients with baseline hematuria and pyuria also had an inferior
postoperative AKI prognosis when compared to those without the urinalysis
abnormalities. CONCLUSION: Baseline dipstick urinalysis may predict postoperative
AKI and may be significantly associated with prognosis after surgery. (Surgery
2017;160:XXX-XXX.).
PMID- 29331402
TI - Tailored surgical treatment of duodenal polyposis in familial adenomatous
polyposis syndrome.
AB - BACKGROUND: To review our experience in patients undergoing operative treatment
for duodenal polypoisis associated with familial adenomatous polyposis with an
emphasis on operative approach and long-term outcomes. METHODS: Duodenal
polypoisis associated with familial adenomatous polyposis patients undergoing
operative treatment were studied retrospectively excluding patients with
preoperative duodenal cancer. RESULTS: Of 767 patients in the database, 63 (8.2%)
patients underwent operative treatment: 42 (67%) pancreas-sparing duodenectomy,
15 (24%) pancreatoduodenectomy, and 6 (9.5%) segmental duodenal resection; the
majority for Spigelman stages III and IV polyposis. Overall 9.6% had
adenocarcinoma postoperatively (28.6% in the pancreatoduodenectomy group; P =
.01). The proportion of Spigelman stages III and IV with cancer were 9.5% and
6.5%, respectively. Pathologic upgrade to cancer in patients with low grade
dysplasia and high-grade dysplasia on preoperative biopsy was 5.7% and 6.7%,
respectively (P = .13). At a median follow-up of 16 years, 7.7% needed a second
duodenal polypoisis associated with familial adenomatous polyposis-related
operation. Progression to high grade dysplasia or cancer in the stomach occurred
in 15.4% of patients. Median overall survival and recurrence-free survival was at
least 16 years and 15.6 years. No significant group-based differences were noted
on follow-up. CONCLUSION: The majority of patients with duodenal polypoisis
associated with familial adenomatous polyposis can achieve long-term, cancer-free
survival with organ-preserving approaches (pancreas-sparing-duodenectomy and
segmental-duodenal-resection) with survival not dependent on the type of
resection.
PMID- 29331403
TI - Anatomy of change: a Kodak moment.
PMID- 29331404
TI - Reliability and validity of the adapted Resistance Training Skills Battery for
Children.
AB - OBJECTIVES: Resistance training (RT) is emerging as a training modality to
improve motor function and facilitate physical activity participation in children
across the motor proficiency spectrum. Although RT competency assessments have
been established and validated among adolescent cohorts, the extent to which
these methods are suitable for assessing children's RT skills is unknown. This
project aimed to assess the psychometric properties of the adapted Resistance
Training Skills Battery for Children (RTSBc), in children with varying motor
proficiency. DESIGN: Repeated measures design with 40 participants (M age=8.2+/
1.7years) displaying varying levels of motor proficiency. METHODS: Participants
performed the adapted RTSBc on two occasions, receiving a score for their
execution of each component, in addition to an overall RT skill quotient child
(RTSQc). Cronbach's alpha, intra-class correlation (ICC), Bland-Altman analysis,
and typical error were used to assess test-retest reliability. To examine
construct validity, exploratory factor analysis was performed alongside computing
correlations between participants' muscle strength, motor proficiency, age, lean
muscle mass, and RTSQc. RESULTS: The RTSBc displayed an acceptable level of
internal consistency (alpha=0.86) and test-retest reliability (ICC range=0.86
0.99). Exploratory factor analysis supported internal test structure, with all
six RT skills loading strongly on a single factor (range 0.56-0.89). Analyses of
structural validity revealed positive correlations for RTSQc in relation to motor
proficiency (r=0.52, p<0.001) and strength scores (r=0.61, p<0.001). CONCLUSIONS:
Analyses revealed support for the construct validity and test-retest reliability
of the RTSBc, providing preliminary evidence that the RTSBc is appropriate for
use in the assessment of children's RT competency.
PMID- 29331405
TI - Reliability and Validity of the Turkish Version of the Consensus Auditory
Perceptual Evaluation of Voice (CAPE-V).
AB - OBJECTIVES: The main purpose of this study was to culturally adapt the Consensus
Auditory-Perceptual Evaluation of Voice (CAPE-V) to Turkish and to evaluate its
internal consistency, validity, and reliability. MATERIALS AND METHODS: The
Turkish version of CAPE-V was developed, and with the use of a prospective case
control design, the voice recordings of 130 participants were collected according
to CAPE-V protocol. Auditory-perceptual evaluation was conducted according to
CAPE-V and Grade, Roughness, Breathiness, Asthenia, and Strain (GRBAS) scale by
two ear, nose, and throat specialists and two speech and language therapists. The
different types of voice disorders, classified as organic and functional
disorders, were compared in terms of their CAPE-V scores. RESULTS: The overall
severity parameter had the highest intrarater and inter-reliability values for
all the participants. For all four raters, the differences in the six CAPE-V
parameters between the study and the control groups were found to be
statistically significant. Among the correlations for the comparable parameters
of the CAPE-V and the GRBAS scales, the highest correlation was found between the
overall severity-grade parameters. There was no difference found between the
organic and functional voice disorders in terms of the CAPE-V scores.
CONCLUSIONS: The Turkish version of CAPE-V has been proven to be a reliable and
valid instrument to use in the auditory-perceptual evaluation of voice. For the
future application of this study, it would be important to investigate whether
cepstral measures correlate with the auditory-perceptual judgments of dysphonia
severity collected by a Turkish version of the CAPE-V.
PMID- 29331406
TI - Effect of Auditory-Perceptual Training With Natural Voice Anchors on Vocal
Quality Evaluation.
AB - PURPOSE: To analyze the effects of auditory-perceptual training with anchor
stimuli of natural voices on inter-rater agreement during the assessment of vocal
quality. STUDY DESIGN: This is a quantitative nature study. METHODS: An auditory
perceptual training site was developed consisting of Programming Interface A, an
auditory training activity, and Programming Interface B, a control activity. Each
interface had three stages: pre-training/pre-interval evaluation,
training/interval, and post-training/post-interval evaluation. Two experienced
evaluators classified 381 voices according to the GRBASI scale (G-grade, R
roughness, B-breathiness, A-asthenia, S-strain, I-instability). Voices were
selected that received the same evaluation by both evaluators: 57 voices for
evaluation and 56 for training were selected, with varying degrees of deviation
across parameters. Fifteen inexperienced evaluators were then selected. In the
pre-, post-training, pre-, and postinterval stages, evaluators listened to the
voices and classified them via the GRBASI scale. In the stage interval evaluators
read a text. In the stage training each parameter was trained separately.
Evaluators analyzed the degrees of deviation of the GRBASI parameters based on
anchor stimuli, and could only advance after correctly classifying the voices. To
quantify inter-rater agreement and provide statistical analyses, the AC1
coefficient, confidence intervals, and percentage variation of agreement were
employed. RESULTS: Except for the asthenia parameter, decreased agreement was
observed in the control condition. Improved agreement was observed with auditory
training, but this improvement did not achieve statistical significance.
CONCLUSION: Training with natural voice anchors suggest an increased inter-rater
agreement during perceptual voice analysis, potentially indicating that new
internal references were established.
PMID- 29331407
TI - Decreased health-related quality of life in children and adolescents with
autoimmune hepatitis.
AB - OBJECTIVE: The objective of this study was to evaluate the health-related quality
of life in children and adolescents with autoimmune hepatitis. METHODS: A cross
sectional assessment with the Pediatric Quality of Life Inventory 4.0 (PedsQL
4.0) was completed for 80 patients with autoimmune hepatitis and 45 healthy
controls. Demographic data, prednisone dose, disease remission state, disease
severity, and abdominal pain were also evaluated. RESULTS: Based on the child
self-reports, physical, emotional, school, and total scores were significantly
lower in autoimmune hepatitis patients when compared with controls (p<0.05).
Based on the parental reports, only the physical and total scores were
significantly lower in autoimmune hepatitis patients versus controls (p<0.05).
Further analysis in autoimmune hepatitis patients with abdominal pain in the last
month revealed significantly lower physical, social, and total median scores
(p<0.05). No differences were observed based on disease remission state or
disease severity (p>0.05). Autoimmune hepatitis patients who received a
prednisone dose below 0.16mg/kg/day at the time of the interview showed
significantly higher physical scores than those who received a dose similar to or
above 0.16mg/kg/day (87.5 [50-100] vs. 75 [15.63-100], p=0.006). CONCLUSIONS:
Reduced scores in the physical, emotional, and school domains were observed in
pediatric autoimmune hepatitis patients compared to control patients. Abdominal
pain and corticosteroid dose negatively influenced the health-related quality of
life in children and adolescents with autoimmune hepatitis.
PMID- 29331408
TI - Long-term craniofacial morphology in young adults treated for a non-syndromal
UCLP: A systematic review.
AB - Minimizing mid-facial growth impairment is one of the treatment goals in cleft
lip and palate surgery. As growth of the maxilla extends into young adulthood,
long-term evaluation is essential to make a comprehensive assessment of a
treatment protocol. There are numerous treatment approaches for cleft lip/palate
surgery, and most have the characteristic distinction between either an early or
a late cleft palate closure. PRISMA guidelines were applied to explore the
quality of the current literature and to identify treatment factors influencing
long-term cephalometric outcomes. The literature search was conducted in Pubmed,
The Cochrane Library and Embase. We included studies evaluating cephalometric
outcomes (SNA and ANB values on 2D cephalograms) in UCLP patients with a mean age
of 16 years and older. Studies with an inadequate description of the timing of
surgery were excluded. 17 studies comprising 906 patients were selected and
included for critical appraisal. Treatment protocols differed considerably among
the included studies and inconsistent methodology was common. Eight studies
applied a one-stage procedure, 11 studies performed a two-stage reconstruction,
and five studies made use of a vomer flap. Applying a multivariate model, we did
not identify any treatment factors that significantly influenced growth (SNA/ANB
values), except for the method of inclusion, suggesting the presence of
significant selection bias within the studies. The current literature remains
inadequate for evidence-based decision making and to advise parents if an early
or late palate closure leads to a more favorable maxillary outgrowth. This
manuscript will propose guidelines and recommended quality criteria for future
studies.
PMID- 29331409
TI - Spreader graft placement: Location, location, location.
PMID- 29331410
TI - Implementing CRISPR-Cas technologies in conventional and non-conventional yeasts:
Current state and future prospects.
AB - Within five years, the CRISPR-Cas system has emerged as the dominating tool for
genome engineering, while also changing the speed and efficiency of metabolic
engineering in conventional (Saccharomyces cerevisiae and Schizosaccharomyces
pombe) and non-conventional (Yarrowia lipolytica, Pichia pastoris syn.
Komagataella phaffii, Kluyveromyces lactis, Candida albicans and C. glabrata)
yeasts. Especially in S. cerevisiae, an extensive toolbox of advanced CRISPR
related applications has been established, including crisprTFs and gene drives.
The comparison of innovative CRISPR-Cas expression strategies in yeasts presented
here may also serve as guideline to implement and refine CRISPR-Cas systems for
highly efficient genome editing in other eukaryotic organisms.
PMID- 29331411
TI - Tailoring cyanobacterial cell factory for improved industrial properties.
AB - Photosynthetic biomanufacturing provides a promising solution for sustainable
production of biofuels and biochemicals. Cyanobacteria are among the most
promising microbial platforms for the construction of photosynthetic cell
factories. Metabolic engineering of cyanobacteria has enabled effective
photosynthetic synthesis of diverse natural or non-natural metabolites, while
commercialization of photosynthetic biomanufacturing is usually restricted by
process and economic feasibilities. In actual outdoor conditions, active cell
growth and product synthesis is restricted to narrow light exposure windows of
the day-night cycles and is threatened by diverse physical, chemical, and
biological environmental stresses. For biomass harvesting and bioproduct
recovery, energy and cost consuming processing and equipment is required, which
further decreases the economic and environmental competitiveness of the entire
process. To facilitate scaled photosynthetic biomanufacturing, lots of efforts
have been made to engineer cyanobacterial cell properties required by robust &
continual cultivation and convenient & efficient recovery. In this review, we
specifically summarized recently reported engineering strategies on optimizing
industrial properties of cyanobacterial cells. Through systematically re-editing
the metabolism, morphology, mutualism interaction of cyanobacterial chassis
cells, the adaptabilities and compatibilities of the cyanobacterial cell
factories to the industrial process could be significantly improved. Cell growth
and product synthesis of the tailored cyanobacterial cells could be expanded and
maintained at night and in stressful environments, while convenient biomass
harvesting could also be expected. For developing more feasible cyanobacterial
photosynthetic biomanufacturing in large scale, we here propose the importance of
tailoring industrial properties of cyanobacteria and outline the directions that
should be exploited in the future.
PMID- 29331412
TI - Anti-leukemic effects of PPARgamma ligands.
AB - The peroxisome proliferator-activated receptor (PPAR) gamma, a subtype of PPARs,
is a member of the nuclear receptor family. PPARgamma and its ligands contribute
to various types of diseases including cancer. Given that currently developed
therapies against leukemia are not very effective or safe, PPARgamma ligands have
been shown to be a new class of compounds with the potential to treat hematologic
malignancies, particularly leukemia. The capability of PPARgamma ligands to
induce apoptosis, inhibit proliferation, and promote differentiation of leukemia
cells suggests it has significant potential as a drug against leukemia. However,
the specific mechanisms and molecules involved are not well-understood, although
a number of PPARgamma ligands with anti-leukemic effects have been identified.
This may explain why PPARgamma ligands have not been widely evaluated in clinical
trials. To fill the gaps in the lack of understanding of specific anti-leukemic
processes of PPARgamma ligands and further adapt these molecules as anti-leukemic
agents, this review describes previous studies of the anti-leukemic effects of
PPARgamma ligands.
PMID- 29331413
TI - eEF-2 Kinase-targeted miR-449b confers radiation sensitivity to cancer cells.
AB - The roles of microRNA in regulation of various biological processes and in
modulation of therapeutic effects have been widely appreciated. In this study, we
found a positive correlation between miR-449 b expression and radiation
sensitivity in cancer cells and in tumor specimens from patients. We showed that
eEF-2 kinase, a negative regulator of global protein synthesis, is a target of
miR-449 b. Introducing a miR-449 b mimic into cancer cells led to suppression of
eEF-2 kinase expression, leading to increases of protein synthesis and depletion
of cellular ATP. Further, we demonstrated that the miR-449 b mimic rendered the
cancer cells more sensitive to ionizing radiation both in vitro (cell culture)
and in vivo (animal xenograft model). Moreover, the radiation sensitivity
conferred by miR-449 b could be blunted by cycloheximide, an inhibitor of protein
synthesis, or by direct delivery of ATP liposome, supporting eEF-2 kinase as a
mediator of the radio-sensitizing effects of miR-449 b. These results indicate
that miR-449 b, which is frequently down-regulated in radio-resistant cancers,
may represent a new critical determinant of radio-sensitivity.
PMID- 29331415
TI - Nogo-B receptor promotes epithelial-mesenchymal transition in non-small cell lung
cancer cells through the Ras/ERK/Snail1 pathway.
AB - Nogo-B receptor (NgBR) is a specific receptor of Nogo-B that regulates vascular
remodeling and angiogenesis. Previously, we found that NgBR promotes the membrane
translocation and activation of Ras in breast cancer cells and enhances the
chemoresistance of hepatocellular carcinoma cells to 5-fluorouracil. However, the
role of NgBR in lung cancer has not yet been elucidated. In the present study, we
found that NgBR knockdown inhibited epithelial-mesenchymal transition (EMT) in
non-small cell lung cancer (NSCLC) cells in vitro and metastasis of NSCLC cells
in vivo. In contrast, NgBR overexpression promoted EMT in and lung metastasis of
NSCLC cells. At the molecular level, NgBR modulated the expression of EMT-related
proteins and enhanced the protein expression of Snail1, a crucial transcription
factor that represses epithelial cell protein marker E-cadherin. Moreover, we
found that NgBR overexpression promoted the membrane localization of Ras and
activation of downstream MEK/ERK signaling pathway and that NgBR knockdown by
using a specific shRNA inversely affected the expression of EMT-related proteins
in NSCLC cells. Thus, our results provide novel insights on the regulatory role
of NgBR in the metastasis of NSCLC that should be investigated further for
developing a therapeutic strategy for treating patients with NSCLC.
PMID- 29331414
TI - Inhibition of FASN and ERalpha signalling during hyperglycaemia-induced matrix
specific EMT promotes breast cancer cell invasion via a caveolin-1-dependent
mechanism.
AB - Since disturbed metabolic conditions such as obesity and diabetes can be critical
determinants of breast cancer progression and therapeutic failure, we aimed to
determine the mechanism responsible for their pro-oncogenic effects. Using non
invasive, epithelial-like ERalpha-positive MCF-7 and T47D human breast cancer
cells we found that hyperglycaemia induced epithelial to mesenchymal transition
(EMT), a key programme responsible for the development of metastatic disease.
This was demonstrated by loss of the epithelial marker E-cadherin together with
increases in mesenchymal markers such as vimentin, fibronectin and the
transcription factor SLUG, together with an enhancement of cell growth and
invasion. These phenotypic changes were only observed with cells grown on
fibronectin and not with those plated on collagen. Analyzing metabolic
parameters, we found that hyperglycaemia-induced, matrix-specific EMT promoted
the Warburg effect by upregulating glucose uptake, lactate release and specific
glycolytic enzymes and transporters. We showed that silencing of fatty acid
synthase (FASN) and the downstream ERalpha, which we showed previously to mediate
hyperglycaemia-induced chemoresistance in these cells, resulted in suppression of
cell growth: however, this also resulted in a dramatic enhancement of cell
invasion and SLUG mRNA levels via a novel caveolin-1-dependent mechanism.
PMID- 29331416
TI - Deubiquitinating enzyme PSMD14 promotes tumor metastasis through stabilizing
SNAIL in human esophageal squamous cell carcinoma.
AB - The epithelial-mesenchymal transition (EMT) transcription factor SNAIL is
associated with distant metastasis and poor prognosis of esophageal squamous cell
carcinoma (ESCC) patients. The proteolysis of SNAIL is mediated by the ubiquitin
proteasome system. Several E3 ligases have been characterized to promote SNAIL
ubiquitination and degradation. However, the reverse process - deubiquitination
of SNAIL remains largely unknown. In this study, we performed a mass spectrometry
to examine the interaction between SNAIL and deubiquitinating enzyme(s).
Subsequently, the deubiquitinating enzyme PSMD14 was identified to target SNAIL
for deubiquitination and stabilization. Furthermore, knockdown of PSMD14
significantly blocks SNAIL-induced EMT and then suppresses tumor cell migration
and invasion in vitro and tumor metastasis in vivo. In addition, the high
expression level of PSMD14 predicts poor prognosis for esophageal cancer
patients. These findings suggest PSMD14 as a bona fide deubiquitinating enzyme to
regulate SNAIL at the post-translational level and provide a promising
therapeutic strategy against tumor metastasis of esophageal cancer.
PMID- 29331417
TI - Down-regulation of RIP3 potentiates cisplatin chemoresistance by triggering HSP90
ERK pathway mediated DNA repair in esophageal squamous cell carcinoma.
AB - Receptor interacting protein kinase 3 (RIP3) is a critical regulator of
programmed necrotic cell death. Here, we observed that RIP3 was significantly
down-regulated in esophageal cancer. And its remaining expression was associated
with better response to chemotherapy and prolonged survival. Notably, re
expression of kinase-dead RIP3 also restored cisplatin sensitivity, suggesting
that some roles of RIP3 beyond necroptosis may be involved in cisplatin-based
chemosensitivity. To investigate the mechanisms, a large-scale quantitative
proteomics study was performed after cisplatin treatment in RIP3-knockdown cells.
In total, approximately 7000 protein groups were confidently identified, with a
false discovery rate of 0.21% at the protein level. Of these proteins, 685
displayed RIP3-dependent changes in abundance. Bioinformatics analyses indicated
that DNA repair pathway was stimulated after RIP3 depletion. Functional studies
showed that deficient RIP3 upregulated FOSL1 and POLD1 through activation of the
HSP90/CDC37 complex and ERK phosphorylation in multiple cell lines. Furthermore,
via inhibition of the HSP90/CDC37 complex, ERK and FOSL1 reversed the cisplatin
resistance phenotype. These results suggest that RIP3 regulates cisplatin
sensitivity through both pronecrotic and non-necrotic functions. RIP3 may be a
potential marker for predicting chemosensitivity.
PMID- 29331418
TI - Non-coding RNAs in cancer stem cells.
AB - Cancer stem cells (CSCs) have been shown to play a key role in tumor initiation,
progression, metastasis, and therapy resistance. Despite their potential clinical
importance, the mechanism of CSC regulation is not well understood. Recent
evidence suggests that different types of non-coding RNAs (ncRNA), such as
microRNA (miRNA) and long non-coding RNA (LncRNA), play a role in regulating CSC
growth and replication by modulating transcription factors and downstream
signaling pathways activated in CSCs. Here, we review the recent major findings
about how they affect stem cell quality acquisition and maintenance in CSCs, as
well as metastasis and therapy resistance. Drawing connections between such
discoveries could be conducive to the development of novel ncRNA-based
therapeutics that can selectively target CSCs and reduce rates of cancer
recurrence.
PMID- 29331419
TI - The therapeutic potential of human adipose-derived mesenchymal stem cells
producing CXCL10 in a mouse melanoma lung metastasis model.
AB - Interferon gamma-induced protein 10 kDa (IP-10) is a potent chemoattractant and
has been suggested to enhance antitumor activity and mediate tumor regression
through multiple mechanisms of action. Multiple lines of evidence have indicated
that genetically-modified adult stem cells represent a potential source for cell
based cancer therapy. In the current study, we assessed therapeutic potential of
human adipose derived mesenchymal stem cells (hADSC) genetically-modified to
express IP-10 for the treatment of lung metastasis in an immunocompetent mouse
model of metastatic melanoma. A Piggybac vector encoding IP-10 was employed to
transfect hADSC ex vivo. Expression and bioactivity of the transgenic protein
from hADSCs expressing IP-10 were confirmed prior to in vivo studies. Our results
indicated that hADSCs expressing IP-10 could inhibit the growth of B16F10
melanoma cells and significantly prolonged survival. Immunohistochemistry
analysis, TUNEL assay and western blot analysis indicated that hADSCs expressing
IP-10 inhibited tumor cell growth, hindered tumor infiltration of Tregs,
restricted angiogenesis and significantly prolonged survival. In conclusion, our
results demonstrated that targeting metastatic tumor sites by hADSC expressing IP
10 could reduce melanoma tumor growth and lung metastasis.
PMID- 29331420
TI - Dacomitinib antagonizes multidrug resistance (MDR) in cancer cells by inhibiting
the efflux activity of ABCB1 and ABCG2 transporters.
AB - The development of multidrug resistance (MDR) to chemotherapy remains a major
challenge in the treatment of cancer. Numerous mechanisms have been recognized
that cause MDR, but one of the most important mechanisms is overexpression of
adenosine triphosphate (ATP)-binding cassette (ABC) transporters, through which
the efflux of various anticancer drugs against their concentration gradients is
powered by ATP. In recent years, small molecular tyrosine kinase inhibitors
(TKIs) have been developed for treatment in various human cancers overexpressing
epidermal growth factor receptor (EGFR). At the same time, some TKIs have been
shown to be capable of inhibiting ABC transporter-mediated MDR. Dacomitinib (PF
00299804) is a second generation, irreversible TKI, which has shown positive
anticancer activities in some preclinical and clinical trials. As many TKIs are
substrates or inhibitors of ABC transporters, this study investigates whether
dacomitinib could interact with ABC subfamily members that mediate MDR, including
ABCB1 (P-gp), ABCG2 (BCRP) and ABCC1 (MRP1). The results showed that dacomitinib
at 1.0 MUM significantly reversed drug resistance mediated by ABCB1 and ABCG2,
but not ABCC1, doing so by antagonizing the drug efflux function in ABCB1- and
ABCG2-overexpressing cell lines. The reversal effect on ABCB1-overexpressing
cells is more potent than that on ABCG2-overexpressing cells. In addition,
dacomitinib at reversal concentration affected neither the protein expression
level nor the localization of ABCB1 and ABCG2. Therefore, the mechanisms of this
modulating effect are likely to be the following: first, as an inhibitor of ABCB1
or ABCG2 transporters, dacomitinib binds to drug-substrate site in transmembrane
domains (TMD) stably in a noncompetitive manner; or second, dacomitinib inhibits
ATPase activity and maintains the stability of TMD conformation in a
concentration-dependent manner thereby inhibiting the drug efflux function of
ABCB1 or ABCG2 transporter. This study provides a useful combinational
therapeutic strategy with dacomitinib and substrates of ABCB1 and/or ABCG2
transporters in ABCB1- or ABCG2-overexpressing cancers.
PMID- 29331421
TI - Hyperglycaemia-induced miR-301a promotes cell proliferation by repressing p21 and
Smad4 in prostate cancer.
AB - Hyperglycaemia promotes the development of Prostate cancer (PCa). However, the
roles of miRNAs in this disease process and the underlying mechanisms are largely
unknown. In this study, we recruited 391 PCa patients in China and found that PCa
patients with high level blood glucose (>=100 mg/dL) trended to have high Gleason
score (GS >= 7). miRNA-301a levels were significantly higher in prostate cancer
than that in normal prostate tissues. Hyperglycaemia or high glucose treatment
induced miR-301a expression in prostate tissues or PCa cell lines. miR-301a
suppressed the expression of p21 and Smad4, and subsequently promoted G1/S cell
cycle transition and cell proliferation in vitro and xenograft growth in nude
mice in vivo. Furthermore, knockdown of p21 and Smad4 mimicked the effects of miR
301a overexpression. Restoration of p21 and smad4 could interrupt the effects of
miR-301a overexpression. Importantly, inhibition of miR-301a severely blocked
high glucose-induced PCa cell growth both in vitro and in vivo. These results
revealed a novel molecular link between hyperglycaemia and PCa. The miR-301a
plays an important role in the hyperglycaemia-associated cancer growth, and
represents a novel therapeutic target for PCa.
PMID- 29331422
TI - FePt-Cys nanoparticles induce ROS-dependent cell toxicity, and enhance chemo
radiation sensitivity of NSCLC cells in vivo and in vitro.
AB - FePt-Cys nanoparticles (FePt-Cys NPs) have been well used in many fields, despite
their poor solubility and stability. We synthetized a cysteine surface modified
FePt NPs, which exhibited good solubility, stability and biocompatibility. We
explored the insight mechanisms of the antitumor effects of this new nanoparticle
system in lung cancer cells. In the in vitro study, FePt-Cys NPs induced a
reactive oxygen species (ROS) burst, which suppressed the antioxidant protein
expression and induced cell apoptosis. Furthermore, FePt-Cys NPs prevented the
migration and invasion of H1975 and A549 cells. These changes were correlated
with a dramatic decrease in MMP-2/9 expression and enhanced the cellular
attachment. We demonstrated that FePt-Cys NPs promoted the effects of chemo
radiation through activation of the caspase system and impairment of DNA damage
repair. In the in vivo study, no severe allergies or drug-related deaths were
observed and FePt-Cys NPs showed a synergistic effect with cisplatin and
radiation. In conclusion, with good safety and efficacy, FePt-Cys NPs could
therefore be potential sensitizers for chemoradiotherapy.
PMID- 29331423
TI - Thymidylate synthase prompts metastatic progression through the dTMP associated
EMT process in pancreatic ductal adenocarcinoma.
AB - As a fundamental metabolic enzyme, anti-Thymidylate synthase (TS) strategy has
been shown to be an effective therapy for human cancers. However, the genuine
effects of TS in pancreatic ductal adenocarcinoma (PDA) are still conflicting. We
systemically assessed the prognostic value and whether TS associated with
malignant progression in PDA. Protein and mRNA expression level of TS were
evaluated in en bloc PDA samples, the prognostic effect of TS expressed in
cytoplasm or cytonuclear was determined separately in the first time. The impact
of TS on tumor cell behaviors was assessed in in vitro assays, and the TS
associated metastatic potential was further determined in two different PDA
metastatic models. The retrospective clinical analysis firstly demonstrated that
tumor cytonuclear TS expression was positively correlated with lymphatic
metastasis and negatively correlated with the overall survival (OS) in PDA
patients. The subsequent experiments further confirmed that TS depletion can
effectively abate EMT (epithelial to mesenchymal) process in in vitro and decline
most of the metastatic lesions in two different PDA mice models, and the
deoxythymidine monophosphate (dTMP) biosynthesis malfunction resulted imbalanced
dNTP pools may be the fundamental causation. Collectively, the present study
suggested the prospective strategy of combined anti-TS scheme for metastatic PDA,
and we strongly suggest further clinical standardization research with a large
cohort to verify the prognostic value and the therapeutic potential of TS in PDA.
PMID- 29331424
TI - Ultra-narrow surface lattice resonances in plasmonic metamaterial arrays for
biosensing applications.
AB - When excited over a periodic metamaterial lattice of gold nanoparticles (~
100nm), localized plasmon resonances (LPR) can be coupled by a diffraction wave
propagating along the array plane, which leads to a drastic narrowing of plasmon
resonance lineshapes (down to a few nm full-width-at-half-maximum) and the
generation of singularities of phase of reflected light. These phenomena look
very promising for the improvement of performance of plasmonic biosensors, but
conditions of implementation of such diffractively coupled plasmonic resonances,
also referred to as plasmonic surface lattice resonances (PSLR), are not always
compatible with biosensing arrangement implying the placement of the
nanoparticles between a glass substrate and a sample medium (air, water). Here,
we consider conditions of excitation and properties of PSLR over arrays of glass
substrate-supported single and double Au nanoparticles (~ 100-200nm), arranged in
a periodic metamaterial lattice, in direct and Attenuated Total Reflection (ATR)
geometries, and assess their sensitivities to variations of refractive index (RI)
of the adjacent sample dielectric medium. First, we identify medium (PSLRair,
PSLRwat for air and water, respectively) and substrate (PSLRsub) modes
corresponding to the coupling of individual plasmon oscillations at medium- and
substrate-related diffraction cut-off edges. We show that spectral sensitivity of
medium modes to RI variations is determined by the lattice periodicity in both
direct and ATR geometries (~ 320nm per RIU change in our case), while substrate
mode demonstrates much lower sensitivity. We also show that phase sensitivity of
PSLR can exceed 105 degrees of phase shift per RIU change and thus outperform the
relevant parameter for all other plasmonic sensor counterparts. We finally
demonstrate the applicability of surface lattice resonances in plasmonic
metamaterial arrays to biosensing using standard streptavidin-biotin affinity
model. Combining advantages of nanoscale architectures, including drastic
concentration of electric field, possibility of manipulation at the nanoscale
etc, and high phase and spectral sensitivities, PSLRs promise the advancement of
current state-of-the-art plasmonic biosensing technology toward single molecule
label-free detection.
PMID- 29331425
TI - Low-picomolar, label-free procalcitonin analytical detection with an electrolyte
gated organic field-effect transistor based electronic immunosensor.
AB - Herein a label-free immunosensor based on electrolyte-gated organic field-effect
transistor (EGOFET) was developed for the detection of procalcitonin (PCT), a
sepsis marker. Antibodies specific to PCT were immobilized on the poly-3
hexylthiophene (P3HT) organic semiconductor surface through direct physical
adsorption followed by a post-treatment with bovine serum albumin (BSA) which
served as the blocking agent to prevent non-specific adsorption. Antibodies
together with BSA (forming the whole biorecognition layer) served to selectively
capture the procalcitonin target analyte. The entire immunosensor fabrication
process was fast, requiring overall 45min to be completed before analyte sensing.
The EGOFET immunosensor showed excellent electrical properties, comparable to
those of bare P3HT based EGOFET confirming reliable biosensing with bio
functional EGOFET immunosensor. The detection limit of the immunosensor was as
low as 2.2pM and within a range of clinical relevance. The relative standard
deviation of the individual calibration data points, measured on immunosensors
fabricated on different chips (reproducibility error) was below 7%. The developed
immunosensor showed high selectivity to the PCT analyte which was evident through
control experiments. This report of PCT detection is first of its kind among the
electronic sensors based on EGOFETs. The developed sensor is versatile and
compatible with low-cost fabrication techniques.
PMID- 29331426
TI - Hybrid porous thin films: Opportunities and challenges for sensing applications.
AB - In this paper, the scientific progress in the field of thin film materials and
their associated sensing technologies are described comprehensively to address
the directions for future research and developments as per the need of modern-day
technologies. To begin with, we briefly discussed the fundamental synthesis
approaches for advanced thin films with an emphasis on the properties necessary
for controlled fabrication (e.g., the elemental ratio and spatial arrangement).
Subsequently, we explored the control, characterization, and optimization of
hybrid porous thin films with respect to diverse sensing applications. The
application of hybrid porous thin film materials has also been discussed in
relation to the mechanisms used for biological, optical, electrical, acoustic,
and other advanced sensing techniques (e.g., surface-enhanced Raman scattering
(SERS)). Finally, conclusions are drawn to highlight the current status of thin
film-based sensing technology along with its opportunities and challenges.
PMID- 29331427
TI - Water-soluble mercury ion sensing based on the thymine-Hg2+-thymine base pair
using retroreflective Janus particle as an optical signaling probe.
AB - Herein, we report an optical sensing platform for mercury ions (Hg2+) in water
based on the integration of Hg2+-mediated thymine-thymine (T-T) stabilization, a
biotinylated stem-loop DNA probe, and a streptavidin-modified retroreflective
Janus particle (SA-RJP). Two oligonucleotide probes, including a stem-loop DNA
probe and an assistant DNA probe, were utilized. In the absence of Hg2+, the
assistant DNA probe does not hybridize with the stem-loop probe due to their T-T
mismatch, so the surface-immobilized stem-loop DNA probe remains a closed hairpin
structure. In the presence of Hg2+, the DNA forms a double-stranded structure
with the loop region via Hg2+-mediated T-T stabilization. This DNA hybridization
induces stretching of the stem-loop DNA probe, exposing biotin. To translate
these Hg2+-mediated structural changes in DNA probe into measurable signal, SA
RJP, an optical signaling label, is applied to recognize the exposed biotin. The
number of biospecifically bound SA-RJPs is proportional to the concentration of
Hg2+, so that the concentration of Hg2+ can be quantitatively analyzed by
counting the number of RJPs. Using the system, a highly selective and sensitive
measurement of Hg2+ was accomplished with a limit of detection of 0.027nM.
Considering the simplified optical instrumentation required for retroreflection
based RJP counting, RJP-assisted Hg2+ measurement can be accomplished in a much
easier and inexpensive manner. Moreover, the detection of Hg2+ in real drinking
water samples including tap and commercial bottled water was successfully carried
out.
PMID- 29331428
TI - Heating enhanced sensitive and selective electrochemical detection of Hg2+ based
on T-Hg2+-T structure and exonuclease III-assisted target recycling amplification
strategy at heated gold disk electrode.
AB - A sensitive and selective electrochemical Hg2+ sensor was developed based on T
Hg2+-T structure and exonuclease (Exo) III -assisted target recycling
amplification at heated gold disk electrode (HAuDE). First, a DNA signal probe P1
was for the first time designed and labeled with ferrocene (Fc) near the attached
SH-5'-end, so as to shorten the distance between Fc and the electrode and enhance
the initial current of Fc compared with that labeled at the 3'-end far from the
electrode. Then the signal amplification was achieved by Exo III-assisted Hg2+
recycling. Briefly, the P1 was complementary to the assistant DNA P2 except the T
T mismatches. In the presence of Hg2+, the P1 self-assembled on the HAuDE could
hybridize with P2 and form DNA duplex with blunt end at the 3'- terminus,
triggering Exo III to stepwise digest mononucleotides from the 3'-terminus of P1,
ultimately liberating Hg2+ and P2, which could be "recycled", resulting in the
digestion of a large amount of P1 and significantly decrease the amount of Fc.
The electrochemical signal difference before and after digestion was proportional
to the Hg2+ concentration. Furthermore, during the digestion period, the Exo III
activity could be significantly increased by elevating the electrode temperature,
great improving the sensitivity and efficiency for Hg2+ detection. A detection
limit of 6.2 pM (S/N = 3) could be obtained with an electrode temperature of 40
degrees C during 60min digestion period, which was lower ca. two magnitudes than
that at 0 degrees C and one magnitude than that at 25 degrees C.
PMID- 29331429
TI - Paper-based fluorescent sensor via aggregation induced emission fluorogen for
facile and sensitive visual detection of hydrogen peroxide and glucose.
AB - Hydrogen peroxide (H2O2), an important reactive oxygen species (ROS), is related
to the oxidative stress in organisms, and plays important roles in a variety of
cellular activities as well. So it is of crucial importance to develop sensitive
and accurate sensing strategies to detect H2O2 in biological systems. Herein, by
taking advantage of the unique emission characteristics of aggregation induced
emission (AIE) fluorogens, we proposed a non-enzymatic fluorescence platform for
facile and sensitive detection of H2O2, both in solution state using fluorescence
spectrometer and on paper-based sensor via visual inspection. Through the
reaction between L-cysteine and H2O2, the fluorescence of TPE-M-L, an AIE
fluorogen formed between maleimide-functionalized tetraphenylethene (TPE-M) and L
cysteine, is quenched, and highly sensitive non-enzymatic H2O2 assay is readily
carried out. The limit of detection (LOD) of 10nM in solution state and 2.5MUM on
paper-based sensor were obtained for H2O2 detection, which were superior or
comparable to those previously reported in literature. Moreover, by integrating
glucose oxidase with the AIE fluorogen of TPE-M-L, highly sensitive and selective
glucose detection was also conveniently achieved both in solution state and on
paper-based sensor by the as-proposed strategy, with the LODs of 50nM in solution
state and 10MUM via visual observation, much better than those obtained by other
fluorescence methods. The as-proposed sensing strategy was also successfully
applied to assay glucose in human serum samples. Therefore, the paper-based
fluorescence sensor exhibits the advantages of simple fabrication, high
sensitivity and portability, and has great potential to be applied in on-site
assay of H2O2 and glucose in real samples.
PMID- 29331431
TI - Robust synchronization of master-slave chaotic systems using approximate model:
An experimental study.
AB - Robust synchronization of master slave chaotic systems are considered in this
work. First an approximate model of the error system is obtained using the ultra
local model concept. Then a Continuous Singular Terminal Sliding-Mode (CSTSM)
Controller is designed for the purpose of synchronization. The proposed approach
is output feedback-based and uses fixed-time higher order sliding-mode (HOSM)
differentiator for state estimation. Numerical simulation and experimental
results are given to show the effectiveness of the proposed technique.
PMID- 29331430
TI - Disposable inkjet-printed electrochemical platform for detection of clinically
relevant HER-2 breast cancer biomarker.
AB - Rapidly fabricated, disposable sensor platforms hold tremendous promise for point
of-care detection. Here, we present an inexpensive (< $0.25) fully inkjet printed
electrochemical sensor with integrated counter, reference, and working electrodes
that is easily scalable for commercial fabrication. The electrochemical sensor
platform featured an inkjet printed gold working 8-electrode array (WEA) and
counter electrode (CE), along with an inkjet -printed silver electrode that was
chlorinated with bleach to produce a Ag/AgCl quasi-reference electrode (RE). As
proof of concept, the electrochemical sensor was successfully applied for
detection of clinically relevant breast cancer biomarker Human Epidermal Growth
Factor Receptor 2 (HER-2). Capture antibodies were bound to a chemically modified
surface on the WEA and placed into a microfluidic device. A full sandwich
immunoassay was constructed following a simultaneous injection of target protein,
biotinylated antibody, and polymerized horseradish peroxide labels into the
microfluidic device housing the WEA. With an ultra fast assay time, of only
15mins a clinically relevant limit of detection of 12pgmL-1 was achieved.
Excellent reproducibility and sensitivity were observed through recovery assays
preformed in human serum with recoveries ranging from 76% to 103%. These easily
fabricated and scalable electrochemical sensor platforms can be readily adapted
for multiplex detection following this rapid assay protocol for cancer
diagnostics.
PMID- 29331432
TI - Sliding mode control for a two-joint coupling nonlinear system based on extended
state observer.
AB - A two-joint coupling nonlinear system driven by pneumatic artificial muscles is
introduced in this paper. A sliding mode controller with extended state observer
is proposed to cope with nonlinearities and disturbances for the two-joint
coupling nonlinear system. In addition, convergence of the extended state
observer is presented and stability analysis of the closed-loop system is also
demonstrated with the sliding mode controller. Lastly, some experiments are
carried out to show the reality effectiveness of the proposed method.
PMID- 29331433
TI - Receding horizon Hinfinity guaranteed cost tracking control for microwave heating
medium with temperature-dependent permittivity.
AB - This paper considers the temperature spectrum tracking control of microwave
heating model, in the presence of asymmetrical input saturation, nonhomogeneous
Neumann boundary condition and temperature-dependent permittivity. The sufficient
condition for the existence of receding horizon Hinfinity guaranteed cost control
is proposed based on the derived finite-dimensional ordinary differential
equation (ODE) error model. Furthermore, by on-line updating and solving linear
matrix inequalities (LMIs) optimization problem, the constrained tracking
controller can be obtained in the sense of minimizing Hinfinity norm and
satisfying the quadratic cost performance. The proposed control strategy is
implemented on a one-dimensional cavity heating model and its performance is
evaluated through the simulation.
PMID- 29331434
TI - Fault diagnosis of rolling element bearing using a new optimal scale morphology
analysis method.
AB - Periodic transient impulses are key indicators of rolling element bearing
defects. Efficient acquisition of impact impulses concerned with the defects is
of much concern to the precise detection of bearing defects. However, transient
features of rolling element bearing are generally immersed in stochastic noise
and harmonic interference. Therefore, in this paper, a new optimal scale
morphology analysis method, named adaptive multiscale combination morphological
filter-hat transform (AMCMFH), is proposed for rolling element bearing fault
diagnosis, which can both reduce stochastic noise and reserve signal details. In
this method, firstly, an adaptive selection strategy based on the feature energy
factor (FEF) is introduced to determine the optimal structuring element (SE)
scale of multiscale combination morphological filter-hat transform (MCMFH).
Subsequently, MCMFH containing the optimal SE scale is applied to obtain the
impulse components from the bearing vibration signal. Finally, fault types of
bearing are confirmed by extracting the defective frequency from envelope
spectrum of the impulse components. The validity of the proposed method is
verified through the simulated analysis and bearing vibration data derived from
the laboratory bench. Results indicate that the proposed method has a good
capability to recognize localized faults appeared on rolling element bearing from
vibration signal. The study supplies a novel technique for the detection of
faulty bearing.
PMID- 29331435
TI - Complications of chronic total occlusion percutaneous coronary intervention:
Subepicardial hematoma.
AB - A 67-year-old man with coronary artery disease and previous coronary underwent
successful Guideliner reverse CART percutaneous coronary intervention of a
chronic total occlusion of the right coronary artery. He later developed evidence
of myocardial ischemia, and imaging, including angiogram, echocardiogram, and
cardiac computed tomography revealing active dye extravasation from the
previously normal RV marginal branches, in addition to a large subepicardial
hematoma. Despite these dramatic findings, the patient remained hemodynamically
stable and pain-free, with resolving ECG changes. Thus, with close clinical
observation, the patient did not undergo pericardiocentesis or other invasive
procedures, and was discharged home safely. This review evaluates the
complications of CTO-PCI, with a focus on subepicardial hematomas, discussing
diagnosis and management of this highly morbid complication.
PMID- 29331436
TI - Jetstream Atherectomy System treatment of femoropopliteal arteries: Results of
the post-market JET Registry.
AB - OBJECTIVES: To report on procedural, safety, and effectiveness outcomes of real
world practice with the Jetstream rotational atherectomy system for treatment of
femoropopliteal artery lesions. BACKGROUND: Safety and effectiveness of treatment
with the Jetstream device has been demonstrated in clinical trials, but outcomes
during real-world clinical practice have yet to be examined. METHODS: 241
patients (66% male, mean age 67years, 41% diabetes; Rutherford 1-3) with de novo
or restenotic (non-stent) femoropopliteal lesions >=4cm in length were recruited.
Major adverse events (MAE), defined as amputation, death, target lesion/vessel
revascularization (TLR/TVR), myocardial infarction, or angiographic distal
embolization that required a separate intervention; and binary restenosis were
assessed at 30days and 12months. RESULTS: The mean (+/-SD) lesion length was
16.4+/-13.6cm; 35% of patients received adjunctive stents. Procedural success was
achieved for 98.3% of lesions. The 30-day MAE rate was 2% (5/219; 2 TLR/TVR and 3
distal embolization); there were no deaths, index limb amputations, or myocardial
infarctions. At 12months, the overall estimated freedom from TLR/TVR was 81.7%
and 77.2% (44/57) of patients were free from duplex ultrasound-assessed
restenosis. Efficacy and patency in a diabetic subset were similar to those of
the overall cohort, while maintaining a similar safety profile. CONCLUSION: In a
cohort reflecting real-world practice, the Jetstream Atherectomy System
demonstrated a high procedural success rate with a low rate of complications and
reinterventions, especially given the relatively long lesions studied.
PMID- 29331437
TI - Influence of operator experience and PCI volume on transfemoral access
techniques: A collaboration of international cardiovascular societies.
AB - INTRODUCTION: Transfemoral access (TFA) is widely used for coronary angiography
and percutaneous coronary intervention (PCI). The influence of operator age,
gender, experience, and procedural volume on performance of femoral arterial
access has not been studied. METHODS: A survey instrument was developed and
distributed via e-mail from professional societies to interventional
cardiologists worldwide from March to December 2016. RESULTS: A total of 988
physicians from 88 countries responded to the survey. TFA is the preferred
approach for patients with cardiogenic shock, left main or bifurcation PCI, and
procedures with mechanical circulatory support. Older (<50years: 56.4%;
>=50years: 66.8%, p<0.0039) and high PCI volume operators (<100 PCI: 57.3%; 100
299 PCI: 58.7%; >=300 PCI: 64.3%, p<0.134) preferred palpation only without
imaging (fluoroscopy or ultrasound (US)) for TFA. Most respondents preferred not
to use micropuncture needle to puncture the femoral artery. Older (>=50years:
64.4%; <50years: 71.5%, p<0.04) and high PCI volume operators (>=300 PCI: 64.1%;
100-299 PCI: 72.6%; <100 PCI: 67.9%, p<0.072) tended not to perform femoral
angiography (FA). Of those performing FA, the majority opted to do it at the end
of the procedure. CONCLUSION: Despite best practice guideline recommendations,
older and high PCI volume interventional cardiologists prefer not to use imaging
for femoral access or perform femoral angiography during TF procedures. These
data highlight opportunities to further reduce TFA complications.
PMID- 29331438
TI - Characterization of surface properties of glass vials used as primary packaging
material for parenterals.
AB - The appropriate selection of adequate primary packaging, such as the glass vial,
rubber stopper, and crimp cap for parenteral products is of high importance to
ensure product stability, microbiological quality (integrity) during storage as
well as patient safety. A number of issues can arise when inadequate vial
material is chosen, and sole compliance to hydrolytic class I is sometimes not
sufficient when choosing a glass vial. Using an appropriate pre-treatment, such
as surface modification or coating of the inner vial surface after the vial
forming process the glass container quality is often improved and interactions of
the formulation with the surface of glass may be minimized. This study aimed to
characterize the inner surface of different type I glass vials (Exp33, Exp51,
Siliconized, TopLyoTM and Type I plus(r)) at the nanoscale level. All vials were
investigated topographically by colorimetric staining and Scanning Electron
Microscopy (SEM). Glass composition of the surface was studied by Time-of-Flight
Secondary Ion Mass Spectrometry (ToF-SIMS) and X-ray Photoelectron Spectroscopy
(XPS), and hydrophobicity/hydrophilicity of the inner surface was assessed by dye
tests and surface energy measurements. All containers were studied unprocessed,
as received from the vendor, i.e. in unwashed and non-depyrogenized condition.
Clear differences were found between the different vial types studied. Especially
glass vials without further surface modifications, like Exp33 and Exp51 vials,
showed significant (I) vial-to-vial variations within one vial lot as well as
(II) variations along the vertical axis of a single vial when studying topography
and chemical composition. In addition, differences and heterogeneity in surface
energy were found within a given tranche (circumferential direction) of Exp51 as
well as Type I plus(r) vials. Most consistent quality was achieved with TopLyoTM
vials. The present comprehensive characterization of surface properties of the
different vial types may serve as basis to further guide the selection of
adequate primary packaging based on the desired quality target product profile
and to support studies of glass surface interactions with formulations. The
proposed analytical method panel can be used for characterization of future glass
vials either before delivery to the manufacturer or drug product manufacturing.
PMID- 29331439
TI - Interactions of dimethylaminoethyl methacrylate copolymer with non-acidic drugs
demonstrated high solubilization in vitro and pronounced sustained release in
vivo.
AB - Recent work demonstrated remarkable solubilization effects of methacrylate
copolymer Eudragit EPO (EPO) not only with acidic drugs but interestingly also
with poorly soluble basic compounds. The current work studied EPO-mediated
solubilization effects first in vitro using felodipine (FLP) and tamoxifen (TMX)
as model compounds. EPO-containing solutions were subsequently compared in a rat
pharmacokinetic study against reference solutions and suspensions. Surprisingly,
solution formulations with EPO did not result in an increased relative oral
bioavailability. Exposure was reduced for both drugs and plasma-profiles of the
EPO solutions showed a delayed and lower maximum plasma concentration compared to
the reference formulations. This sustained in vivo release was likely due to
combined effects of strong drug-polymer interactions and pH-dependent
precipitation of the polymer in the rat intestine. Remarkable was that in vitro
drug-polymer coprecipitates did not reveal crystalline drug by polarized light
microscopy. Thus, such a formulation approach provides a rather simple
opportunity to modify drug release in vivo. However, this may be rather an
approach for preclinical formulations, if high peak-to-trough ratios of plasma
levels are problematic regarding adverse effects related to Cmax or if plasma
concentrations drop too fast below required pharmacological concentrations.
PMID- 29331440
TI - The effect of bilateral eye-movements versus no eye-movements on sexual
fantasies.
AB - BACKGROUND AND OBJECTIVES: Bilateral eye-movements (EMs) and visual mental
imagery both require working memory resources. When performed together, they
compete for these resources, which can cause various forms of mental imagery to
become impaired (e.g., less vivid). This study aimed to examine whether EMs
impair sexual fantasies (a form of mental imagery) in the same manner. METHODS:
Eighty undergraduates (40 males, 40 females) took part in four counterbalanced
conditions: (1) EMs and an experience-based sexual fantasy; (2) EMs and an
imagination-based sexual fantasy; (3) experience-based sexual fantasy only; and
(4) imagination-based sexual fantasy only. In each condition, the vividness,
emotionality, and arousability of the sexual fantasy were rated pre- and post
task. All three variables were predicted to decrease in the EM conditions.
RESULTS: Sexual fantasies were reported as less vivid, positive, and arousing
after performing concurrent EMs relative to fantasising only, for both memory-
and imagination-based sexual fantasies. There were no gender differences. Demand
did not appear to account for the effects. LIMITATIONS: Self-report measures were
used rather than objective measures. Working memory taxation and capacity were
not directly assessed. Also, negatively appraised sexual fantasies were not
targeted and a 'no intervention' control was not included. CONCLUSIONS: Bilateral
EMs were effective at impairing the phenomenological properties of sexual mental
imagery, extending the literature on EM effects. Given the potential clinical
implications, future research should focus on validating and extending these
results, for example, by targeting negatively appraised sexual fantasies
(including problematic and offense-related) and incorporating a 'no intervention'
condition.
PMID- 29331441
TI - Poor oral intake in a late preterm twin - usual symptom with an unusual
diagnosis.
AB - BACKGROUND: At three weeks of age, a previous 34 weeks' gestation male infant
(twin A) was transferred to our regional perinatal center (RPC) with complaints
of poor oral feeding and intermittent tachypnea. Twin B was discharged at 37
weeks with an uneventful course. CASE: Twin A briefly required respiratory
support but continued to have difficulty transitioning from gavage to oral
feeding. Initially, his inability to feed orally was thought to be secondary to
nasal congestion and prematurity, but with worsening respiratory distress he was
transferred for further evaluation and management. DIAGNOSIS & CONCLUSION: On
admission to RPC, the examination prompted a cardiac assessment which revealed a
large aortic-pulmonary window type II. After surgery, the infant quickly improved
and went home on-demand oral feeds. Cardiac lesions are more common in
monochorionic twins but should be suspected in dichorionic twins especially if
one twin has a normal course.
PMID- 29331442
TI - Coffee consumption and risk of hypertension in the SUN Project.
AB - BACKGROUND & AIMS: Evidence on coffee consumption and its association with the
incidence of hypertension is still inconsistent. The aim of this study was to
examine the association of regular or decaffeinated coffee consumption with the
risk of developing hypertension in a middle-aged Mediterranean cohort. METHODS:
The SUN Project is a prospective open cohort with more than 22,500 Spanish
university graduates. For the present study, we analyzed data from 13,374
participants initially free of hypertension (mean follow-up 9.1 years). The
consumption of regular and decaffeinated coffee was obtained at baseline using a
previously validated semi-quantitative food frequency questionnaire. Validated,
self-reported medical diagnoses of hypertension were collected biennially. We
used Cox regression models to estimate hazard ratios (HR) and 95% confidence
intervals (95% CI) for incident hypertension according to baseline coffee
consumption. We assessed the interaction with sex and baseline adherence to the
Mediterranean diet. RESULTS: Among 121,397 person-years of follow-up, a total of
1757 participants developed hypertension. Overall, coffee consumption -either
caffeinated or decaffeinated- was not significantly associated with the risk of
hypertension. Only among women, higher consumption of regular coffee was
associated with a 26% lower risk of hypertension (>=2 cups/d vs. never/seldom,
95% CI 9%-39%; p for interaction: 0.0236). Women with a low baseline adherence to
the Mediterranean diet showed the strongest risk reduction (HR >= 2 cups/d vs.
never/seldom 0.58, 95% CI (0.41-0.82) p for interaction = 0.0452). CONCLUSION: In
the SUN project we found an inverse association between regular coffee
consumption and the risk of hypertension in women, which was strongest among
women with a suboptimal food pattern (low adherence to the Mediterranean diet).
PMID- 29331443
TI - Strengthen federal regulation of laboratory-developed and direct-to-consumer
genetic testing.
PMID- 29331444
TI - Call for action: Nurses must play a critical role to enhance health literacy.
PMID- 29331445
TI - The vital role of school nurses in ensuring the health of our nation's youth.
PMID- 29331446
TI - Intolerance of uncertainty: Neural and psychophysiological correlates of the
perception of uncertainty as threatening.
AB - Intolerance of uncertainty (IU) reflects the perception of uncertainty as
threatening, regardless of the true probability of threat. IU is elevated in
various forms of psychopathology, uniquely associated with anxiety and depression
symptoms after controlling for related constructs, and prospectively predicts
symptoms. Given the ubiquity of uncertainty in daily life and the clinical
implications of IU, recent work has begun to investigate the neural and
psychophysiological correlates of IU. This review summarizes the existing
literature and integrates findings within a mechanistic neural model of
responding to uncertainty. IU is associated with heightened reactivity to
uncertainty reflected in greater activity of the anterior insula and amygdala,
alterations in neural responses to rewards and errors evident in event-related
potentials, a mixed pattern of startle responses to uncertain threat, and
deficiencies in safety learning indexed by startle and skin conductance
responding. These findings provide evidence of disruptions in several domains of
responding to uncertainty, threat, and reward associated with IU that may confer
risk for the development of psychopathology. Significant attention is devoted to
recommendations for future research, including consideration of the complex
interplay of IU with emotion regulation, cognitive control, and reward
processing.
PMID- 29331448
TI - Surveillance After Endovascular Treatment for Blunt Thoracic Aortic Injury.
PMID- 29331451
TI - Sporotrichoid non-tuberculous mycobacterial infections following anti-TNF
treatment.
PMID- 29331447
TI - Sharp-wave ripples as a signature of hippocampal-prefrontal reactivation for
memory during sleep and waking states.
AB - It is widely believed that memories that are encoded and retrieved during waking
behavior are consolidated during sleep. Recent studies on the interactions
between the hippocampus and the prefrontal cortex have greatly advanced our
understanding of the physiological bases of these memory processes. Although
hippocampal-prefrontal network activity differs in many aspects during waking and
sleep states, here we review evidence that hippocampal sharp-wave ripples (SWRs)
emerge as a common neurophysiological pattern in both states, facilitating
communication between these two regions via coordinated reactivation of stored
memory information. We further consider whether sleep and awake reactivation
mediate similar memory processes or have different mnemonic functions, and the
mechanistic role of this cross-regional dialogue in learning and memory. Finally,
we provide an integrated view of how these two forms of reactivation might work
together to support spatial learning and memory.
PMID- 29331450
TI - Mapping stimulus feature selectivity in macaque V1 by two-photon Ca2+ imaging:
Encoding-model analysis of fluorescence responses to natural movies.
AB - In vivo calcium (Ca2+) imaging using two-photon microscopy allows activity to be
monitored simultaneously from hundreds of individual neurons within a local
population. While this allows us to gain important insights into how cortical
neurons represent sensory information, factors such as photo-bleaching of the
Ca2+ indicator limit imaging duration (and thus the numbers of stimuli that can
be tested), which in turn hampers the full characterization of neuronal response
properties. Here, we demonstrate that using an encoding model combined with
presentation of natural movies results in detailed characterization of receptive
field (RF) properties despite the relatively short time for data collection.
During presentation of natural movie clips to macaque monkeys, we recorded
fluorescence signals from primary visual cortex (V1) neurons that had been loaded
with a Ca2+ indicator. For each recorded neuron, we constructed an encoding model
that comprised an array of motion-energy filters that tiled over the RFs. We
optimized the weight of each filter's output so that the linear sum of the
outputs across the filters mimicked the neuron's Ca2+-signal responses. These
models were able to predict the neural responses to a different set of natural
movies with a significant degree of accuracy. Moreover, the orientation tunings
of neurons simulated by the model were highly correlated with those
experimentally obtained when grating stimuli were presented to the monkeys. The
model predictions were also consistent with what is known about spatial frequency
tunings, the structure of excitatory subfields of RFs (i.e., classical RFs), and
functional maps for these RF properties in V1. Further analysis revealed a new
aspect of V1 functional architecture; the extent and distribution of suppressive
RF subfields varied among nearby neurons, while those for excitatory subfields
were shared. Thus, applying our encoding-model analysis to two-photon Ca2+
imaging of neuronal responses to natural movies provides a reliable and efficient
means of analyzing a wide range of RF properties in multiple neurons imaged in a
local region.
PMID- 29331449
TI - Quantifying axonal responses in patient-specific models of subthalamic deep brain
stimulation.
AB - Medical imaging has played a major role in defining the general anatomical
targets for deep brain stimulation (DBS) therapies. However, specifics on the
underlying brain circuitry that is directly modulated by DBS electric fields
remain relatively undefined. Detailed biophysical modeling of DBS provides an
approach to quantify the theoretical responses to stimulation at the cellular
level, and has established a key role for axonal activation in the therapeutic
mechanisms of DBS. Estimates of DBS-induced axonal activation can then be coupled
with advances in defining the structural connectome of the human brain to provide
insight into the modulated brain circuitry and possible correlations with
clinical outcomes. These pathway-activation models (PAMs) represent powerful
tools for DBS research, but the theoretical predictions are highly dependent upon
the underlying assumptions of the particular modeling strategy used to create the
PAM. In general, three types of PAMs are used to estimate activation: 1) field
cable (FC) models, 2) driving force (DF) models, and 3) volume of tissue
activated (VTA) models. FC models represent the "gold standard" for analysis but
at the cost of extreme technical demands and computational resources.
Consequently, DF and VTA PAMs, derived from simplified FC models, are typically
used in clinical research studies, but the relative accuracy of these
implementations is unknown. Therefore, we performed a head-to-head comparison of
the different PAMs, specifically evaluating DBS of three different axonal
pathways in the subthalamic region. The DF PAM was markedly more accurate than
the VTA PAMs, but none of these simplified models were able to match the results
of the patient-specific FC PAM across all pathways and combinations of stimulus
parameters. These results highlight the limitations of using simplified
predictors to estimate axonal stimulation and emphasize the need for novel
algorithms that are both biophysically realistic and computationally simple.
PMID- 29331452
TI - Design, synthesis and evaluation of gamma-turn mimetics as LSD1-selective
inhibitors.
AB - Lysine-specific demethylase 1 (LSD1) is an attractive molecular target for cancer
therapy. We have previously reported potent LSD1-selective inhibitors (i.e.,
NCD18, NCD38, and their analogs) consisting of trans-2-phenylcyclopropylamine
(PCPA) or trans-2-arylcyclopropylamine (ACPA) and a lysine moiety that could form
a gamma-turn structure in the active site of LSD1. Herein we report the design,
synthesis and evaluation of gamma-turn mimetic compounds for further improvement
of LSD1 inhibitory activity and anticancer activity. Among a series of gamma-turn
mimetic compounds synthesized by a Mitsunobu-reaction-based amination strategy,
we identified 1n as a potent and selective LSD1 inhibitor. Compound 1n induced
cell cycle arrest and apoptosis through histone methylation in human lung cancer
cells. The gamma-turn mimetics approach should offer new insights into drug
design for LSD1-selective inhibitors.
PMID- 29331454
TI - Reply.
PMID- 29331453
TI - Are privacy-enhancing technologies for genomic data ready for the clinic? A
survey of medical experts of the Swiss HIV Cohort Study.
AB - PURPOSE: Protecting patient privacy is a major obstacle for the implementation of
genomic-based medicine. Emerging privacy-enhancing technologies can become key
enablers for managing sensitive genetic data. We studied physicians' attitude
toward this kind of technology in order to derive insights that might foster
their future adoption for clinical care. METHODS: We conducted a questionnaire
based survey among 55 physicians of the Swiss HIV Cohort Study who tested the
first implementation of a privacy-preserving model for delivering genomic test
results. We evaluated their feedback on three different aspects of our model:
clinical utility, ability to address privacy concerns and system usability.
RESULTS: 38/55 (69%) physicians participated in the study. Two thirds of them
acknowledged genetic privacy as a key aspect that needs to be protected to help
building patient trust and deploy new-generation medical information systems. All
of them successfully used the tool for evaluating their patients'
pharmacogenomics risk and 90% were happy with the user experience and the
efficiency of the tool. Only 8% of physicians were unsatisfied with the level of
information and wanted to have access to the patient's actual DNA sequence.
CONCLUSION: This survey, although limited in size, represents the first
evaluation of privacy-preserving models for genomic-based medicine. It has
allowed us to derive unique insights that will improve the design of these new
systems in the future. In particular, we have observed that a clinical
information system that uses homomorphic encryption to provide clinicians with
risk information based on sensitive genetic test results can offer information
that clinicians feel sufficient for their needs and appropriately respectful of
patients' privacy. The ability of this kind of systems to ensure strong security
and privacy guarantees and to provide some analytics on encrypted data has been
assessed as a key enabler for the management of sensitive medical information in
the near future. Providing clinically relevant information to physicians while
protecting patients' privacy in order to comply with regulations is crucial for
the widespread use of these new technologies.
PMID- 29331455
TI - Femtosecond laser-assisted cataract surgery in pediatric patients.
AB - Pediatric cataract surgery poses a significant challenge for the cataract
surgeon, in part because an elastic anterior capsule can make capsulorhexis
difficult. With the use of femtosecond laser-assisted cataract surgery (FLACS),
however, the continuous curvilinear capsulorhexis can be made with predictable
size, circular shape, centration, and accuracy. In addition, topical anesthesia
can be used for the FLACS docking procedure in cooperative children above 6 years
of age, using transparent adhesive polyurethane film segments.
PMID- 29331456
TI - Vocalization as an indicator of estrus climax in Holstein heifers during natural
estrus and superovulation.
AB - The reliable detection of estrus is an important scientific and practical
challenge in dairy cattle farming. Female vocalization may indicate reproductive
status, and preliminary evidence suggests that this information can be used to
detect estrus in dairy cattle. The aim of this study was to associate the changes
in the vocalization rate of dairy heifers with behavioral estrus indicators as
well as test the influence of the type of estrus (natural estrus vs.
superovulation-induced estrus). We analyzed 6 predefined estrus-related behavior
patterns (standing to be mounted, head-side mounting, active mounting, chin
resting, being mounted while not standing, and active sniffing in the anogenital
region) and vocalization rates in the peri-estrus period (day of estrus +/- 1 d)
of 12 German Holstein heifers using audio-visual recordings. Each heifer was
observed under natural estrus and a consecutive superovulation induced by FSH and
cloprostenol. Estrus was determined by behavioral patterns and confirmed by
clinical examination (vaginoscopy and ultrasound imaging of the ovaries) as well
as by the concentration of peripheral progesterone. Estrus behavior and
vocalization rates were analyzed in 3-h intervals (an average of 19 intervals for
each heifer), and an estrus score was calculated based on the 6 behaviors. The
interval with the highest estrus score (I0) was considered the estrus climax. We
demonstrated similar time courses for the estrus score and vocalization rate
independent of estrus type. However, in natural estrus, the maximum vocalization
rate (+/-SE) occurred in the interval before estrus climax (I-1; 42.58 +/- 21.89)
and was significantly higher than that in any other interval except estrus climax
(I0; 27.58 +/- 9.76). During natural estrus, the vocalization rate was
significantly higher within the interval before estrus climax (I-1; 42.58 +/-
21.89 vs. 11.58 +/- 5.51) than under superovulation. The results underscore the
potential use of vocalization rate as a suitable indicator of estrus climax in
automated estrus detection devices. Further studies and technical development are
required to record and process individual vocalization rates.
PMID- 29331457
TI - Effect of the concentration of circulating prolactin on dairy cows'
responsiveness to domperidone injection.
AB - The objective of this study was to determine whether the responsiveness of the
mammary gland to prolactin (PRL) is affected by the concentration of the hormone.
After 1 pre-experimental week (d -7 to -1), 18 Holstein cows in mid to late
lactation were injected intramuscularly twice daily with either 0.5 mg of
quinagolide (QN) or 2 mL of water (control) for 2 wk (d 1 to 14; treatment
period). After the treatment period, all cows received daily subcutaneous
injections of 300 mg of domperidone (DOMP) for 3 wk (d 15 to 35; DOMP period).
The cows were monitored for an additional 2 wk as a posttreatment period (d 36 to
49). Blood and milk samples were collected 3 times per week. Additionally, blood
samples were collected during the a.m. milking on d -4, 14, and 35. Milk
production was not affected by QN during the treatment period but was increased
during the DOMP and posttreatment periods in the QN cows. With respect to milk
composition, the treatments affected only the protein content, which was greater
in the QN cows during the treatment period. Blood PRL concentration declined
during QN injections and was lower in the QN cows than in the control cows
between d 5 and 14. The basal concentration of PRL was increased by DOMP
injections during the DOMP and posttreatment periods but was not affected by
previous QN injections. Prolactin concentration in milk was not affected by the
QN treatments but was increased by DOMP injections during the DOMP and
posttreatment periods. Milking-induced PRL release was decreased by QN on d 14.
On d 35, milking did not induce a significant release of PRL above the baseline
for both treatments. In conclusion, the results of this experiment support the
contention that the mammary gland's responsiveness to PRL is modulated by the
previous level of the hormone.
PMID- 29331458
TI - Genetic correlations between methane production and fertility, health, and body
type traits in Danish Holstein cows.
AB - Our aim was to investigate the genetic correlations between CH4 production and
body conformation, fertility, and health traits in dairy cows. Data were
collected from 10 commercial Holstein herds in Denmark, including 5,758 cows with
records for body conformation traits, 7,390 for fertility traits, 7,439 for
health traits, and 1,397 with individual CH4 measurements. Methane production was
measured during milking in automatic milking systems, using a sniffer approach.
Correlations between CH4 and several different traits were estimated. These
traits were interval between calving and first insemination, interval between
first and last insemination, number of inseminations, udder diseases, other
diseases, height, body depth, chest width, dairy character, top line, and body
condition score. Bivariate linear models were used to estimate the genetic
parameters within and between CH4 and the other traits. In general, the genetic
correlations between CH4 and the traits investigated were low. The heritability
of CH4 was 0.25, and ranged from 0.02 to 0.07 for fertility and health traits,
and from 0.17 to 0.74 for body conformation traits. Further research with a
larger data set should be performed to more accurately establish how CH4 relates
to fertility, health, and body conformation traits in dairy cattle. This will be
useful in the design of future breeding goals that consider the production of
CH4.
PMID- 29331459
TI - Garlic (Allium sativum L.) fed to dairy cows does not modify the cheese-making
properties of milk but affects the color, texture, and flavor of ripened cheese.
AB - Garlic and garlic components have recently been proposed as ruminal activity
modulators to reduce the enteric methane emissions of ruminants, but little is
known of their influence on milk coagulation properties, nutrient recovery,
cheese yield, and sensorial and rheological characteristics of milk and cheese.
The present study assessed the effects of garlic and diallyl sulfide supplements
on dry matter intake (DMI), productive performance, milk coagulation properties,
cheese yield, milk and cheese sensory profiles, and rheological characteristics.
Four dairy cows were fed a total mixed ration either alone (control) or
supplemented with 100 or 400 g/d of garlic cloves or 2 g/d of diallyl sulfide in
4 consecutive experimental periods in a 4 * 4 Latin square design. The diallyl
sulfide dose was established to provide approximately the same amount of allyl
thiosulfinate compounds as 100 g of fresh garlic cloves. The total mixed ration
was composed of 0.29 corn silage, 0.23 corn-barley mixture, 0.17 sunflower
soybean mixture, 0.12 alfalfa hay, 0.12 grass hay, 0.04 sugar beet pulp, and 0.02
other additives, and contained 0.253 starch, 0.130 crude protein, and 0.375
neutral detergent fiber, on a dry matter basis. Each experimental period
consisted of 7 d of transition and 14 d of treatment. On d 18 and 21 of each
period, milk samples (10 L) were collected from each cow for chemical analysis
and cheese-making. The organoleptic properties of the milk and 63-d-ripened
cheeses were assessed by a panel of 7 trained sensory evaluators. The
experimental treatments had no effects on DMI, milk yield, feed efficiency (milk
yield/DMI), milk coagulation properties, nutrient recovery, or cheese yield.
Garlic-like aroma, taste, and flavor of milk and cheese were significantly
influenced by the treatments, particularly the highest dose of garlic cloves, and
we found close exponential relationships between milk and cheese for garlic-like
aroma (R2 = 0.87) and garlic-like flavor (R2 = 0.79). Diallyl sulfide and 400 g/d
of garlic cloves resulted in lower pH, shear force, and shear work of ripened
cheeses compared with the other treatments. Garlic cloves and diallyl sulfide had
opposite effects on cheese color indices. We conclude that adding 400 g/d of
garlic to the feed of lactating dairy cows highly influences the sensory and
rheological characteristics of cheese.
PMID- 29331460
TI - Inhibition of Shigella sonnei-induced epithelial barrier disruption by surface
layer associated proteins of lactobacilli from Chinese fermented food.
AB - Surface-layer associated proteins (SLAP) of Lactobacillus paracasei ssp.
paracasei M5-L and Lactobacillus casei Q8-L were examined to identify the
functional basis for their protection within intestinal epithelial cells. The
results showed that SLAP of M5-L and Q8-L remained active in a trypsin solution
and retained a 45-kDa protein band, similar to that observed in controls. In
contrast, under conditions of simulated gastric juice, the SLAP were partially
degraded. Inhibitory effects of SLAP on adherence of Shigella sonnei to HT-29
cells were assessed with use of exclusion, competition, and replacement assays.
In response to M5-L at 50 MUg/mL SLAP, an inhibition ratio of 33% was obtained,
while for Q8-L at 400 MUg/mL SLAP, the inhibition ratio was 48%. Hoechst 33258
test results showed that cells infected with S. sonnei and co-incubated with SLAP
of M5-L and Q8-L were only partially apoptotic, with apoptosis rates of 37.67 and
43.67%, respectively. These levels of apoptosis were substantially lower than
that observed with cells infected with S. sonnei alone. In addition, the SLAP of
Q8-L and M5-L reduced downstream caspase-1 activity and further modified
apoptotic cell damage. Finally, SLAP of M5-L and Q8-L were also able to prevent
S. sonnei-induced membrane damage by inhibiting delocalization of zonula
occludens (ZO)-1 and reducing the amount of occludin produced by S. sonnei.
PMID- 29331461
TI - Stabilizing vitamin D3 using the molten globule state of alpha-lactalbumin.
AB - alpha-Lactalbumin (alpha-LA) is the second most abundant bovine whey protein. It
has been intensively studied because of its readiness to populate the molten
globular (MG) state, a partially folded state with native levels of secondary
structure but loss of tertiary structure. The MG state of alpha-LA exposes a
significant number of hydrophobic patches that could be used to bind and
stabilize small hydrophobic molecules such as vitamin D3 (vitD). Accordingly, we
tested the ability of alpha-LA to stabilize vitD in a pH interval from 7.4 to 2;
over this pH interval, alpha-LA transitions from the folded state to the MG
state. The MG state stabilized vitD better than the folded state and was superior
to the major bovine whey protein beta-lactoglobulin (beta-LG), which is known to
stabilize vitD. At pH 7.4, beta-LG and alpha-LA stabilized vitD to the same
extent. Tryptophan fluorescence quenching measurements indicated that alpha-LA
has one binding site at pH 7.4 but acquires an additional binding site when the
pH is lowered to pH 2 to 4. Stability measurements of the vitD in the alpha-LA
vitD complex at different temperatures suggest that UHT processing would lead to
little loss of vitD. This study demonstrates the potential of alpha-LA as a
component in vitD fortification, particularly for low pH applications.
PMID- 29331462
TI - Genetic background of methane emission by Dutch Holstein Friesian cows measured
with infrared sensors in automatic milking systems.
AB - International environmental agreements have led to the need to reduce methane
emission by dairy cows. Reduction could be achieved through selective breeding.
The aim of this study was to quantify the genetic variation of methane emission
by Dutch Holstein Friesian cows measured using infrared sensors installed in
automatic milking systems (AMS). Measurements of CH4 and CO2 on 1,508 Dutch
Holstein Friesian cows located on 11 commercial dairy farms were available.
Phenotypes per AMS visit were the mean of CH4, mean of CO2, mean of CH4 divided
by mean of CO2, and their log10-transformations. The repeatabilities of the log10
transformated methane phenotypes were 0.27 for CH4, 0.31 for CO2, and 0.14 for
the ratio. The log10-transformated heritabilities of these phenotypes were 0.11
for CH4, 0.12 for CO2, and 0.03 for the ratio. These results indicate that
measurements taken using infrared sensors in AMS are repeatable and heritable
and, thus, could be used for selection for lower CH4 emission. Furthermore, it is
important to account for farm, AMS, day of measurement, time of day, and
lactation stage when estimating genetic parameters for methane phenotypes.
Selection based on log10-transformated CH4 instead of the ratio would be expected
to give a greater reduction of CH4 emission by dairy cows.
PMID- 29331463
TI - Discriminating aging and protein-to-fat ratio in Cheddar cheese using sensory
analysis and a potentiometric electronic tongue.
AB - The objectives of this study were to evaluate the flavor and taste attributes of
full-fat Cheddar cheeses with different protein-to-fat ratios (PFR) over aging
time using a descriptive sensory analysis panel and a consumer panel, and to
correlate these attributes with instrumental parameters obtained by the
potentiometric electronic tongue. Three Cheddar cheese formulations (PFR of 0.74,
0.85, and 1.01) were produced in triplicate and composition was verified. Cheese
was aged at 7.2 degrees C and evaluated at 2, 5, 8, 10, 11, and 12 mo by a
trained panel (n = 10) for 8 flavor and 5 taste attributes and using an
electronic tongue for 7 nonvolatile taste attributes. Cheese aged for 12 mo was
also evaluated by a consumer sensory panel for liking and intensity attributes.
Principal component analysis was performed to discriminate cheese based on aging
time and PFR, whereas correlation between sensory and instrumental attributes was
assessed using partial least squares regression. Descriptive sensory analysis of
flavor and taste attributes differentiated Cheddar cheeses over aging time, but
not among PFR formulations. The electronic tongue distinguished changes among
cheese samples due to PFR formulation and aging time. The electronic tongue
proved successful in characterizing the nonvolatile flavor components in Cheddar
cheese and correlated with taste perceptions measured by descriptive sensory
analysis. Consumer evaluations showed distinctive attribute profiles for the 3
PFR Cheddar cheese formulations. Overall, higher fat content was associated with
increased flavor intensities in Cheddar cheese and drove consumer acceptability
and purchase intent ratings. The electronic tongue detected smaller changes in
tastes (bitter, metallic, salty, sour, spicy, sweet, and umami) of the 3 PFR
formulations over time when compared with the trained panelists, who detected no
differences, suggesting that the electronic tongue may be more sensitive to
tastants than humans and may have the capability for early detection or
identification of problems in a batch of cheese during aging. Results suggest
taste quality of cheese may be monitored using the electronic tongue with greater
sensitivity than a trained panel, and may be more objective, rapid, and cost
effective than human panelists.
PMID- 29331464
TI - Somatic cell count-based selection reduces susceptibility to energy shortage
during early lactation in a sheep model.
AB - During the transition from late gestation to early lactation ruminants experience
a negative energy balance (NEB), which is considered to increase susceptibility
to mammary infections. Our previous study in 2 divergent lines of sheep selected
for high and low somatic cell score (SCS) suggested an association between the
response to NEB and genetic susceptibility to mastitis. Forty-eight early
lactation primiparous dairy ewes from the 2 SCS genetic lines were allocated to 2
homogeneous subgroups-an NEB group, which was energy restricted and received 60%
of the energy requirements for 15 d, and a control-fed group-to obtain 4 balanced
groups of 12 ewes: high-SCS positive energy balance, low-SCS positive energy
balance, high-SCS NEB, and low-SCS NEB. High-SCS ewes showed greater weight loss
and increased plasmatic concentrations of beta-hydroxybutyrate and nonesterified
fatty acids than low-SCS ewes when confronted with an induced NEB. The aim of
this study was to further characterize this interaction by combining
transcriptomic and phenotypic data with a generalized partial least squares
discriminant analysis using mixOmics package framework. A preliminary analysis
using 3 blocks of phenotypes (fatty acids, weight and production, blood
metabolites) revealed a high correlation between fat-to-protein ratio, beta
hydroxybutyrate, and nonesterified fatty acids concentrations with milk long
chain fatty acid yields. These phenotypes allowed good discrimination of the
energy-restricted high-SCS ewes and confirmed a high level of adipose tissue
mobilization in this group. A second analysis, which included RNA-seq data,
revealed high correlations between the long-chain fatty acid yields in milk and
PDK4, CPT1A, SLC25A20, KLF10, and KLF11 expression, highlighting the relationship
between mobilization of body reserves and enhanced fatty acids utilization for
energy production in blood cells. Finally, analysis of milk composition measured
in 1,025 ewes from the 2 genetic lines over 10 yr confirmed significant higher
fat-to-protein ratio in high-SCS ewes in early lactation. Altogether, our results
strongly confirmed a genetic link between susceptibility to mastitis and
metabolic adaptation to energy shortage. Improving genetic resistance to mastitis
using SCS should be accompanied by a favorable effect on the response to
metabolic stress, especially in highly stressful early lactation. Moreover, this
study suggests that the fat-to-protein ratio could be used as a low-cost tool for
monitoring energy balance and ketosis during this critical phase of lactation.
PMID- 29331465
TI - Genome-wide association study for milk infrared wavenumbers.
AB - Individual wavenumbers of the infrared (IR) spectra of bovine milk have been
shown to be moderately to highly heritable. The objective of this study was to
identify genomic regions associated with individual milk IR wavenumbers. This is
expected to provide information about the genetic background of milk composition
and give insight in the relation between IR wavenumbers and milk components. For
this purpose, a genome-wide association study was performed for a selected set of
50 individual IR wavenumbers measured on 1,748 Dutch Holstein cows. Significant
associations were detected for 28 of the 50 wavenumbers. In total, 24 genomic
regions distributed over 16 bovine chromosomes were identified. Major genomic
regions associated with milk IR wavenumbers were identified on chromosomes 1, 5,
6, 14, 19, and 20. Most of these regions also showed significant associations
with fat, protein, or lactose percentage. However, we also identified some new
regions that were not associated with any one of these routinely collected milk
composition traits. On chromosome 1, we identified 2 new genomic regions and
hypothesized that they are related to variation in milk phosphorus content and
orotic acid, respectively. On chromosome 20, we identified a new genomic region
that seems to be related to citric acid. Identification of genomic regions
associated with milk phosphorus content, orotic acid, and citric acid suggest
that the milk IR spectra contain direct information on these milk components.
Consequently milk IR analyses probably can be used to predict these milk
components, which have low concentrations in milk; this can lead to novel
applications of milk IR spectroscopy for dairy cattle breeding and herd
management.
PMID- 29331466
TI - High-grain diets supplemented with phytogenic compounds or autolyzed yeast
modulate ruminal bacterial community and fermentation in dry cows.
AB - The feeding of concentrate-rich diets may lead to microbial imbalances and
dysfermentation in the rumen. The main objective of this study was to determine
the effects of supplementing phytogenic compounds (PHY) or autolyzed yeast (AY)
on rumen fermentation and microbial abundance in cows intermittently fed
concentrate-rich diets. The experiment was carried out as an incomplete 3 * 4
Latin square design, with 8 nonlactating rumen-fistulated Holstein-Friesian cows.
The cows were randomly assigned to a concentrate diet that was either not
supplemented (CON), or supplemented with PHY or AY. Each of the 4 consecutive
experimental periods was composed of a 1-wk roughage-only diet (RD), 6-d gradual
concentrate increase, followed by 1 wk of 65% concentrate (dry matter basis; Conc
I), and 1 wk of RD and a final 2-wk 65% concentrate (dry matter basis; Conc II)
phase. Digesta samples were collected from the rumen mat for bacterial 16S rRNA
gene Illumina MiSeq (Illumina, Balgach, Switzerland) sequencing, and samples of
particle-associated rumen liquid were obtained for measuring short-chain fatty
acids, lactate, ammonia, and pH during RD (d 6), Conc I (d 19), and Conc II (d
39). The concentrate feeding caused a decrease of overall bacterial diversity
indices, especially during Conc I. The genera Ruminococcus, Butyrivibrio, and
Coprococcus were decreased, whereas Prevotella, Megasphaera, Lachnospira, and
Bacteroides were increased in abundance. Supplementation of both feed additives
increased the abundance of gram-positive and decreased that of gram-negative
bacteria. Supplementation of AY enhanced cellulolytic bacteria such as
Ruminococcus spp., whereas PHY decreased starch and sugar fermenters including
Bacteroides spp., Shuttleworthia spp., and Syntrophococcus spp. Moreover, PHY
supplementation increased butyrate percentage in the rumen in both concentrate
phases. In conclusion, intermittent high-concentrate feeding altered the digesta
associated rumen bacterial community and rumen fermentation with more significant
alterations found in Conc I than in Conc II. The data also showed that both feed
additives had the most significant modulatory effects on the bacterial community,
and their subsequent fermentation, during periods of low pH.
PMID- 29331468
TI - Symposium review: The influences of heat stress on bovine mammary gland function.
AB - Heat stress reduces cow milk yield and results in a significant economic loss for
the dairy industry. During lactation, heat stress lowers milk production by 25 to
40% with half of the decrease in milk synthesis resulting from the reduced feed
intake. In vitro studies indicate that primary bovine mammary epithelial cells
display greater rates of programmed cell death when exposed to high ambient
temperatures, which may lead to a decrease in the total number of mammary
epithelial cells in the mammary gland, partially explaining the lower milk
production of lactating cows under heat stress. The function of mammary cells is
also altered by heat stress. In response to heat stress, mammary cells display
higher gene expression of heat shock proteins, indicating a need for
cytoprotection from protein aggregation and degradation. Further, heat stress
results in increased gene expression without altering protein expression of
mammary epithelial cell junction proteins, and does not substantially influence
the integrity of mammary epithelium. These data suggest that the mammary gland
strives to maintain cell-to-cell junction integrity by synthesizing more proteins
to compensate for protein losses induced by heat stress. During the dry period,
heat stress negatively affects mammary gland development by reducing mammary cell
proliferation before parturition, resulting in a dramatic decrease in milk
production in the subsequent lactation. In addition to mammary growth, the
mammary gland of the heat-stressed dry cow has reduced protein expression of
autophagic proteins in the early dry period, suggesting heat stress influences
mammary involution. Emerging evidence also indicates that heifers born to cows
that experience late-gestation heat stress have lower milk yield during their
first lactation, implying that the maternal environment may alter mammary gland
development of the offspring. It is not clear if this is due to a direct
epigenetic modification of prenatal mammary gland development by maternal heat
stress. More research is needed to elucidate the effect of heat stress on mammary
gland development and function.
PMID- 29331467
TI - Canadian National Dairy Study: Herd-level milk quality.
AB - The objective of this study was to estimate Canadian national milk quality
parameters and estimate the bulk tank milk (BTM) prevalence of 4 mastitis
pathogens, Staphylococcus aureus, Streptococcus agalactiae, Mycoplasma bovis, and
Prototheca spp., on Canadian dairy farms. A questionnaire was sent to all
Canadian dairy producers. Of the 1,062 producers who completed the questionnaire,
374 producers from across the country were visited and milking hygiene was
assessed. Farm-level milk quality data for all Canadian dairy producers was
collected from the provincial marketing boards and combined with the
questionnaire and farm visit data. In addition, a BTM sample was collected either
during the farm visit or by the marketing board in November of 2015 and was
tested for 4 major mastitis pathogens using the PathoProof Mastitis Major 4 PCR
Assay (Thermo Fisher Scientific Inc., Waltham, MA). Apparent herd-level
prevalence was 46% for S. aureus, 6% for Prototheca spp., 0% for M. bovis, and 0%
for Strep. agalactiae. Due to the low prevalence of M. bovis and Strep.
agalactiae and a lack of significant factors associated with farms testing
positive for Prototheca spp., an association analysis could only be carried out
for Staph. aureus-positive farms. Factors associated with Staph. aureus-positive
farms were not fore-stripping cows before milking (odds ratio = 1.87), milking
with a pipeline system (odds ratio = 2.21), and stall bases made of a rubberized
surface (mats and mattresses), whereas protective factors were using blanket dry
cow therapy (odds ratio = 0.49) and applying a tag or visible mark on cows known
to have chronic mastitis infections (odds ratio = 0.45). The Canadian national
production-weighted geometric mean somatic cell count was determined to be
208,000 cells/mL. This is the first national dairy study conducted in Canada.
Participating farms had higher milk yield; were more likely to have a loose
housing system, parlor, or automated milking system; and had lower weighted mean
BTM somatic cell count than the national level. Sampling larger farms with better
milk quality means the apparent prevalence of the 4 mastitis pathogens likely
underestimates the true levels.
PMID- 29331470
TI - The effect of different precooling rates and cold storage on milk microbiological
quality and composition.
AB - The objective of this study was to measure the effect of different milk cooling
rates, before entering the bulk tank, on the microbiological load and composition
of the milk, as well as on energy usage. Three milk precooling treatments were
applied before milk entered 3 identical bulk milk tanks: no plate cooler (NP),
single-stage plate cooler (SP), and double-stage plate cooler (DP). These
precooling treatments cooled the milk to 32.0 +/- 1.4 degrees C, 17.0 +/- 2.8
degrees C, and 6.0 +/- 1.1 degrees C, respectively. Milk was added to the bulk
tank twice daily for 72 h, and the tank refrigeration temperature was set at 3
degrees C. The blend temperature within each bulk tank was reduced after each
milking event as the volume of milk at 3 degrees C increased simultaneously. The
bacterial counts of the milk volumes precooled at different rates did not differ
significantly at 0 h of storage or at 24-h intervals thereafter. After 72 h of
storage, the total bacterial count of the NP milk was 3.90 +/- 0.09 log10 cfu/mL,
whereas that of the precooled milk volumes were 3.77 +/- 0.09 (SP) and 3.71 +/-
0.09 (DP) log10 cfu/mL. The constant storage temperature (3 degrees C) over 72 h
helped to reduce bacterial growth rates in milk; consequently, milk composition
was not affected and minimal, if any, proteolysis occurred. The DP treatment had
the highest energy consumption (17.6 +/- 0.5 Wh/L), followed by the NP (16.8 +/-
2.7 Wh/L) and SP (10.6 +/- 1.3 Wh/L) treatments. This study suggests that
bacterial count and composition of milk are minimally affected when milk is
stored at 3 degrees C for 72 h, regardless of whether the milk is precooled;
however, milk entering the tank should have good initial microbiological quality.
Considering the numerical differences between bacterial counts, however, the use
of the SP or DP precooling systems is recommended to maintain low levels of
bacterial counts and reduce energy consumption.
PMID- 29331469
TI - Peroxisome proliferator-activated receptor delta regulates lipid droplet
formation and transport in goat mammary epithelial cells.
AB - Even though recent evidence in goat mammary epithelial cells (GMEC) suggest a
role of peroxisome proliferator-activated receptor delta (PPARD) in regulating
lipid homeostasis, its role is not fully understood. Our hypothesis was that
PPARD regulates lipid transport processes in GMEC and, thus, plays a crucial role
in regulating fat formation. The PPARD was overexpressed using an adenovirus
system (Ad-PPARD) with recombinant green fluorescent protein (Ad-GFP) as the
control. Results revealed that overexpression of PPARD markedly upregulated the
mRNA abundance of PPARD. Compared with the control (Ad-GFP+dimethyl sulfoxide),
overexpression of PPARD alone had no effect on mRNA expression of CD36, SCD1,
FABP4, ACSL1, and ADRP. The cultures overexpressing PPARD with the PPARD ligand
GW0742 (GW) upregulated the expression of CD36, FABP3, FABP4, ACSL1, and ADRP.
Overexpression of PPARD in GMEC plus GW increased the concentration of 16:1 and
18:1-trans and was associated with upregulation of SCD1. Compared with the
control (Ad-GFP+dimethyl sulfoxide), the decrease of triacylglycerol
concentration coupled with upregulation of genes related to lipid droplet
secretion (e.g., ADRP and ACSL1) induced by PPARD overexpression suggests a role
in lipid droplet (LD) secretion. Luciferase assay revealed that GW increased the
ADRP promoter activity in a dose-dependent manner. Knockdown of PPARD impaired
the increase of ADRP promoter activity induced by GW, whereas GW enhanced the
activity of ADRP promoter in GMEC overexpressing PPARD. Data with the ADRP 5'
flanking truncated luciferase reporter suggest a core region (-1,444 to -990 bp)
response element for the induction of GW. This core region contains a known PPARG
response element (PPRE) at -1,003 to -990 bp. When the PPRE was mutated, the
overexpression of PPARD had no effect on ADRP promoter activity. Collectively,
these results reveal a novel role for PPARD in lipid homeostasis via promoting
fatty acid transport and LD formation through a mechanism of direct binding to
the promoter of key genes. Hence, PPARD activity may contribute to fatty acid
transport and LD formation during lactation.
PMID- 29331471
TI - Symposium review: Novel strategies to genetically improve mastitis resistance in
dairy cattle.
AB - Mastitis is a disease of major economic importance to the dairy cattle sector
because of the high incidence of clinical mastitis and prevalence of subclinical
mastitis and, consequently, the costs associated with treatment, production
losses, and reduced animal welfare. Disease-recording systems compiling data from
a large number of farms are still not widely implemented around the world; thus,
selection for mastitis resistance is often based on genetically correlated
indicator traits such as somatic cell count (SCC), udder depth, and fore udder
attachment. However, in the past years, several countries have initiated
collection systems of clinical mastitis, based on producers recording data in
most cases. The large data sets generated have enabled researchers to assess
incidence of this disease and to investigate the genetic background of clinical
mastitis itself, as well as its relationships with other traits of interest to
the dairy industry. The genetic correlations between clinical mastitis and its
previous proxies were estimated more accurately and confirmed the strong
relationship of clinical mastitis with SCC and udder depth. New traits deriving
from SCC were also studied, with the most relevant findings being associated with
mean somatic cell score (SCS) in early lactation, standard deviation of SCS, and
excessive test-day SCC pattern. Genetic correlations between clinical mastitis
and other economically important traits indicated that selection for mastitis
resistance would also improve resistance against other diseases and enhance both
fertility and longevity. However, milk yield remains negatively correlated with
clinical mastitis, emphasizing the importance of including health traits in the
breeding objectives to achieve genetic progress for all important traits. These
studies enabled the establishment of new genetic and genomic evaluation models,
which are more efficient for selection to mastitis resistance. Further studies
that are potential keys for future improvement of mastitis resistance are deep
investigation of the bacteriology of mastitis, identification of novel indicator
traits and tools for selection, and development of a larger female reference
population to improve reliability of genomic evaluations. These cutting-edge
studies will result in a better understanding of the genetic background of
mastitis resistance and enable a more accurate phenotyping and genetic selection
to improve mastitis resistance, and consequently, animal welfare and industry
profitability.
PMID- 29331472
TI - Influence of partially demineralized milk proteins on rheological properties and
microstructure of acid gels.
AB - Innovative clean label processes employed in the manufacture of acid gels are
targeted to modify the structure of proteins that contribute to rheological
properties. In the present study, CO2-treated milk protein concentrate powder
with 80% protein in dry matter (TMPC80) was mixed with nonfat dry milk (NDM) in
different ratios for the manufacture of acid gels. Dispersions of NDM and TMPC80
that provided 100, 90, 70, and 40% of protein from NDM were reconstituted to 4.0%
(wt/wt) protein and 12.0% (wt/wt) total solids. Dispersions were adjusted to pH
6.5, followed by heat treatment at 90 degrees C for 10 min. Glucono-delta-lactone
was added and samples were incubated at 30 degrees C, reaching pH 4.5 +/- 0.05
after 4 h of incubation. Glucono-delta-lactone levels were adjusted to compensate
for the lower buffering capacity of samples with higher proportions of TMPC80,
which is attributable to the depletion of buffering minerals from both the serum
and micellar phase during preparation of TMPC80. Sodium dodecyl sulfate-PAGE
analysis indicated a higher amount of caseins in the supernatant of unheated
suspensions with increasing proportions of CO2-treated TMPC80, attributable to
the partial disruption of casein micelles in TMPC80. Heat treatment reduced the
level of whey proteins in the supernatant due to the heat-induced association of
whey proteins with casein micelles, the extent of which was larger in samples
containing more micellar casein (i.e., samples with a lower proportion of
TMPC80). Particle size analysis showed only small differences between nonheated
and heated dispersions. Gelation pH increased from ~5.1 to ~5.3, and the storage
modulus of the gels at pH 4.5 increased from ~300 to ~420 Pa when the proportion
of protein contributed by TMPC80 increased from 0 to 60%. Water-holding capacity
also increased and gel porosity decreased with increasing proportion of protein
contributed by TMPC80. The observed gel properties were in line with
microstructural observations by confocal microscopy, wherein sample gels
containing increasing levels of TMPC80 exhibited smaller, well-connected
aggregates with uniform, homogeneous pore sizes. We concluded that TMPC80 can be
used to partially replace NDM as a protein source to improve rheological and
water-holding properties in acid gels. The resultant gels also exhibited
decreased buffering, which can improve the productive capacity of yogurt
manufacturing plants. Overall, the process can be leveraged to reduce the amount
of hydrocolloids added to improve yogurt consistency and water-holding capacity,
thus providing a path to meet consumer expectations of clean label products.
PMID- 29331473
TI - A Randomized Trial of Itraconazole vs Prednisolone in Acute-Stage Allergic
Bronchopulmonary Aspergillosis Complicating Asthma.
AB - OBJECTIVE: Whether itraconazole monotherapy is effective in the acute stage of
allergic bronchopulmonary aspergillosis (ABPA) remains unknown. The goal of this
study was to compare the efficacy and safety of itraconazole and prednisolone
monotherapy in ABPA. METHODS: Treatment-naive subjects with ABPA complicating
asthma (January 2012 to December 2013) were randomized to receive either oral
itraconazole or prednisolone for 4 months. The study was not blinded. The primary
outcomes were proportion of subjects exhibiting a composite response after 6
weeks, percent decline in IgE after treatment, and numbers of subjects
experiencing exacerbation. The secondary outcomes included the time to first
exacerbation, change in lung function, and treatment-related adverse effects.
RESULTS: A total of 131 subjects (prednisolone group, n = 63; itraconazole group,
n = 68) were included in the study. The number of subjects exhibiting a composite
response was significantly higher in the prednisolone group compared with the
itraconazole group (100% vs 88%; P = .007). The percent decline in IgE after 6
weeks and 3 months and the number of subjects with exacerbations after 1 and 2
years of treatment were similar in the two groups. The time to first exacerbation
(mean: 437 vs 442 days) and the improvement in lung function after 6 weeks was
also similar in the two groups. The occurrence of side effects was significantly
higher in the glucocorticoid arm (P < .001). CONCLUSIONS: Prednisolone was more
effective in inducing response than itraconazole in acute-stage ABPA. However,
itraconazole was also effective in a considerable number and, with fewer side
effects compared with prednisolone, remains an attractive alternative in the
initial treatment of ABPA. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01321827;
URL: www.clinicaltrials.gov).
PMID- 29331474
TI - Clinical Databases for Chest Physicians.
AB - A clinical database is a repository of patient medical and sociodemographic
information focused on one or more specific health condition or exposure.
Although clinical databases may be used for research purposes, their primary goal
is to collect and track patient data for quality improvement, quality assurance,
and/or actual clinical management. This article aims to provide an introduction
and practical advice on the development of small-scale clinical databases for
chest physicians and practice groups. Through example projects, we discuss the
pros and cons of available technical platforms, including Microsoft Excel and
Access, relational database management systems such as Oracle and PostgreSQL, and
Research Electronic Data Capture. We consider approaches to deciding the base
unit of data collection, creating consensus around variable definitions, and
structuring routine clinical care to complement database aims. We conclude with
an overview of regulatory and security considerations for clinical databases.
PMID- 29331475
TI - End-of-Life Care for Patients With Advanced Kidney Disease in the US Veterans
Affairs Health Care System, 2000-2011.
AB - BACKGROUND: Little is known about patterns of end-of-life care for patients with
advanced kidney disease not treated with maintenance dialysis. STUDY DESIGN: Case
series. SETTING & PARTICIPANTS: A sample of 14,071 patients with sustained
estimated glomerular filtration rates < 15mL/min/1.73m2 treated in the US
Veterans Affairs health care system who died during 2000 to 2011. Before death,
12,756 of these patients had been treated with dialysis, 503 had been discussing
and/or preparing for dialysis therapy, and for 812, there had been a decision not
to pursue dialysis therapy. OUTCOMES: Hospitalization and receipt of an intensive
procedure during the final month of life, in-hospital death, and palliative care
consultation and hospice enrollment before death. RESULTS: Compared with
decedents treated with dialysis, those for whom a decision not to pursue dialysis
therapy had been made were less often hospitalized (57.3% vs 76.8%; OR, 0.40 [95%
CI, 0.34-0.46]), less often the recipient of an intensive procedure (3.5% vs
24.6%; OR, 0.15 [95% CI, 0.10-0.22]), more often the recipient of a palliative
care consultation (52.6% vs 21.6%; OR, 4.19 [95% CI, 3.58-4.90]), more often used
hospice services (38.7% vs 18.2%; OR, 3.32 [95% CI, 2.83-3.89]), and died less
frequently in a hospital (41.4% vs 57.3%; OR, 0.78 [95% CI, 0.74-0.82]).
Hospitalization (55.5%; OR, 0.39 [95% CI, 0.32-0.46]), receipt of an intensive
procedure (13.7%; OR, 0.60 [95% CI, 0.46-0.77]), and in-hospital death (39.0%;
OR, 0.47 [95% CI, 0.39-0.56]) were also less common among decedents who had been
discussing and/or preparing for dialysis therapy, but their use of palliative
care and hospice services was similar. LIMITATIONS: Findings may not be
generalizable to groups not well represented in the Veterans Affairs health care
system. CONCLUSIONS: Among decedents, patients not treated with dialysis before
death received less intensive patterns of end-of-life care than those treated
with dialysis. Decedents for whom there had been a decision not to pursue
dialysis therapy before death were more likely to receive palliative care and
hospice.
PMID- 29331476
TI - Factors Associated With Withdrawal From Maintenance Dialysis: A Case-Control
Analysis.
AB - BACKGROUND: Little is known about differences in the clinical course between
patients receiving maintenance dialysis who do and do not withdraw from dialysis
therapy. STUDY DESIGN: Case-control analysis. SETTING & PARTICIPANTS: US patients
with Medicare coverage who received maintenance hemodialysis for 1 year or longer
in 2008 through 2011. PREDICTORS: Comorbid conditions, hospitalizations, skilled
nursing facility stays, and a morbidity score based on durable medical equipment
claims. OUTCOME: Withdrawal from dialysis therapy. MEASUREMENTS: Rates of medical
events, hospitalizations, skilled nursing facility stays, and a morbidity score.
RESULTS: The analysis included 18,367 (7.7%) patients who withdrew and 220,443
(92.3%) who did not. Patients who withdrew were older (mean age, 75.3+/-11.5 [SD]
vs 66.2+/-14.1 years) and more likely to be women and of white race, and had
higher comorbid condition burdens. The odds of withdrawal among women were 7%
(95% CI, 4%-11%) higher than among men. Compared to age 65 to 74 years, age 85
years or older was associated with higher adjusted odds of withdrawal (adjusted
OR, 1.61; 95% CI, 1.54-1.68), and age 18 to 44 years with lower adjusted odds
(adjusted OR, 0.36; 95% CI, 0.32-0.40). Blacks, Asians, and Hispanics were less
likely to withdraw than whites (adjusted ORs of 0.36 [95% CI, 0.35-0.38], 0.47
[95% CI, 0.42-0.53], and 0.46 [95% CI, 0.44-0.49], respectively). A higher
durable medical equipment claims-based morbidity score was associated with
withdrawal, even after adjustment for traditional comorbid conditions and
hospitalization; compared to a score of 0 (lowest presumed morbidity), adjusted
ORs of withdrawal were 3.48 (95% CI, 3.29-3.67) for a score of 3 to 4 and 12.10
(95% CI, 11.37-12.87) for a score >=7. Rates of medical events and
institutionalization tended to increase in the months preceding withdrawal, as
did morbidity score. LIMITATIONS: Results may not be generalizable beyond US
Medicare patients; people who withdrew less than 1 year after dialysis therapy
initiation were not studied. CONCLUSIONS: Women, older patients, and those of
white race were more likely to withdraw from dialysis therapy. The period before
withdrawal was characterized by higher rates of medical events and higher levels
of morbidity.
PMID- 29331477
TI - Atypical Presentation of Pregnancy-Related Hemolytic Uremic Syndrome.
AB - The cause of acute kidney injury during pregnancy and in the postpartum period
can be particularly challenging to diagnose, especially when it is necessary to
differentiate among preeclampsia; eclampsia; hemolysis, elevated liver enzymes
and low platelets (HELLP) syndrome; and thrombotic microangiopathies (TMAs). All
these disease entities can present with kidney failure, microangiopathic
hemolytic anemia, and thrombocytopenia. We present a teaching case of atypical
hemolytic uremic syndrome in the postpartum period in a young woman who was found
to have mutations of uncertain clinical significance in the complement cascade,
including in C3, CFH, and CFI. We use this as an opportunity to review the
clinical presentation and pathophysiology of preeclampsia, eclampsia, and the
TMAs. We focus on diagnostic challenges, especially because many patients with
TMA do not present with thrombocytopenia, which can delay diagnosis. We
additionally review the clinical settings in which administration of eculizumab,
a C5 membrane attack complex inhibitor, is appropriate.
PMID- 29331478
TI - Comprehensive analysis of lncRNAs and mRNAs with associated co-expression and
ceRNA networks in C2C12 myoblasts and myotubes.
AB - Long non-coding RNAs (lncRNAs) are emerging as important regulators in the
modulation of muscle development and muscle-related diseases. To explore
potential regulators of muscle differentiation, we determined the expression
profiles of lncRNAs and mRNAs in C2C12 mouse myoblast cell line using microarray
analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway
enrichment analyses were performed to explore their function. We also constructed
co-expression, cis/trans-regulation, and competing endogenous RNA (ceRNA)
networks with bioinformatics methods. We found that 3067 lncRNAs and 3235 mRNAs
were differentially regulated (fold change >=2.0). Bioinformatics analysis
indicated that the principal functions of the transcripts were related to muscle
structure development and morphogenesis. Co-expression analysis showed 261 co
expression relationships between 233 lncRNAs and 10 mRNAs, and nine lncRNAs
interacted with myog and MEF2C collectively. Cis/trans-regulation prediction
revealed that lncRNA Myh6 could be a valuable gene via cis-regulation, and
lncRNAs such as 2310043L19Ris, V00821, and AK139352 may participate in particular
pathways regulated by transcription factors, including myog, myod1, and foxo1.
The myog-specific ceRNA network covered 10 lncRNAs, 378 miRNAs, and 1960 edges.
The upregulated lncRNAs Filip1, Myl1, and 2310043L19Rik may promote myog
expression by acting as ceRNAs. Our results offer a new perspective on the
modulation of lncRNAs in muscle differentiation.
PMID- 29331479
TI - Molecular characterization and expression of Piwil1 and Piwil2 during gonadal
development and treatment with HCG and LHRH-A2 in Odontobutis potamophila.
AB - Piwi proteins play an important regulatory role in germ cell division during
gametogenesis and gonad development. In order to understand the function of Piwi
genes in the reproductive process of the dark sleeper, we identified and
characterized Piwil1 and Piwil2 from gonad tissue. The tissue distribution
demonstrated that Piwils were highly expressed in the gonad of the dark sleeper.
During gonad development, higher expression was observed in stage I of both the
testes and ovaries than in subsequent stages at mRNA and protein levels. The
results of immunohistochemistry demonstrated that Piwils were predominantly
distributed in the spermatogonia, spermatocytes, and early oocytes. When treated
with the HPG axis hormone (HCG and LHRH-A2), the expression of Piwils was
significantly decreased in the testes and ovaries at mRNA and protein levels. All
of these results indicated that Piwils play a vital role in gonad development and
gametogenesis. Our findings provide valuable evidence to further clarify the
underlying modulation mechanism of Piwils in teleosts.
PMID- 29331480
TI - Human papillomavirus (HPV) 18 genetic variants and cervical cancer risk in
Taizhou area, China.
AB - Human papillomavirus (HPV) type 18 is predominantly associated with the
development of cervical adenocarcinomas, whereas data on HPV18 genetic
variability in China are limited. HPV18 genetic variants were formed phylogenetic
tree, including lineages A, B, and C. We aimed to evaluate the diversity of HPV18
genetic variants by sequencing the entire E6, E7 and L1 genes. Between 2012 and
2015, a total of 138 (0.8%, 138/17669) women with single HPV18 infection were
selected in this study. Finally, we observed 122 HPV18 isolates of the complete
E6-E7-L1 sequences, and obtained 36 distinct variation patterns which the
accession GenBank numbers as KY457805-KY457840. Except KY457805, KY457813,
KY457819, KY457827, KY457829, the rest of HPV18 isolates (81.1%, 31/36) are novel
variants. All of HPV18 variants belong to lineage A, while no lineage B, and C
was found in our population of Taizhou region, Southeast China. Sublineage A1 was
the most common variants (85.2%, 104/122), followed by sublineage A4, A3 and A5,
while no sublineage A2 was obtained. Based on the tree topologies, there were
three newly identified candidates' sublineages A6-A8. Out of 122 women, 67
(54.9%) had diagnosed by biopsy, including 49 women who diagnosed with
cervicitis, 12 with cervical intraepithelial neoplasia (CIN)1, 4 with CIN2/3, and
2 with adenocarcinomas, respectively. Nevertheless, there was no association
between HPV18 (sub) lineages and CIN1 or worse (CIN1+) lesions comparing with
normal biopsies (P = .469). In conclusion, knowledge of the distribution of
geographic/ethnical HPV18 genetic diversity provides critical information for
developing diagnostic probes, epidemiologic correlate of cervical cancer risk and
design of HPV vaccines for targeted populations.
PMID- 29331481
TI - Genetic contribution of SUN5 mutations to acephalic spermatozoa in Fujian China.
AB - Acephalic spermatozoa is an extremely rare disease associated with primary
infertility. A recent study showed that genetic alterations in the SUN5 gene lead
to this disease, and SUN5 mutations could explain the disease in about half of
the patients. Therefore, in the present study, to re-visit the genetic
contribution of SUN5 mutations to acephalic spermatozoa, we recruited 15
unrelated affected individuals and screened the SUN5 gene for mutations by whole
exome sequencing (WES) and Sanger sequencing. Five of the 15 (33.33%) subjects
were found to carry the same homozygous mutation in the SUN5 gene c.381delA
(p.V128Sfs*7). Neither homozygous nor compound heterozygous mutations in SUN5
were found in the other 10 patients. The c.381delA mutation resulted in the
truncation of the SUN5 protein and decreased the expression and altered the
distribution of the outer dense fiber 1 (ODF1) protein. Thus, in our study SUN5
mutations accounted for only one-third of the patients in our cohort, which is
lower than the percentage reported previously. Thus, our study suggests that the
contribution of SUN5 mutations to acephalic spermatozoa might not be as high as
described previously. These results will help in the genetic counseling of
patients with acephalic spermatozoa.
PMID- 29331483
TI - GATA4 is a transcriptional regulator of R-spondin1 in Japanese flounder
(Paralichthys olivaceus).
AB - GATA4 is a well-known transcription factor of the GATA family implicated in
regulation of sex determination and gonadal development in mammals. In this
study, we cloned the full-length cDNA of Paralichthys olivaceus gata4 (Po-gata4).
Phylogenetic, gene structure, and synteny analysis showed that Po-GATA4 is
homologous to GATA4 of teleost and tetrapod. Po-gata4 transcripts were detected
in Sertoli cells, spermatogonia, oogonia and oocytes, with higher transcript
levels overall in the testis than the ovary. The promoter region of P. olivaceus
R-spondin1was found to contain a GATA4-binding motif. Results of CBA (cleaved
amplified polymorphic sequence-based binding assay) indicated that GATA4 could
indeed bind to the promoter sequence of R-spondin1. Moreover, human GATA4
recombinant protein could upregulate R-spondin1 in P. olivaceus ovary cells and
FBCs (flounder brain cell line). In FBCs, overexpression of Po-gata4 resulted in
elevated transcript levels of R-spondin1. Taken together, our results indicate
that Po-GATA4 is involved in gonadal development by regulating R-spondin1
expression.
PMID- 29331484
TI - Novel biomolecular information in rotenone-induced cellular model of Parkinson's
disease.
AB - In order to uncover the remarkable pathogenic genes or molecular pathological
process in Parkinson's disease (PD), we employed a microarray analysis upon the
cellular PD model induced by rotenone. Compared to the control group, 2174 genes
were screened out to be expressed differently in the rotenone-induced group by
certain criterion. GO analysis and the pathways analysis showed the significant
enrichment of genes that were associated with the biological process of cell
cycle, apoptotic process, organelle fusion, mitochondrial lesion, endoplasmic
reticulum stress and so on. Among these significant DE genes, some were sorted
out to be involved in cell cycle and protein processing in endoplasmic reticulum.
As the PPI network analysis showed, the interaction relationship of the DEGs
involved in the process of protein generation in endoplasmic reticulum(ER) was
clearly showed up. As a prediction, we emphasized the genes EDEM1, ATF4, TRAF2
might play central roles in the protein misfolding process during the progression
of Parkinson's disease and these new-found genes might be the future research
focus and therapeutic targets in PD.
PMID- 29331485
TI - Impact of 9p21.3 region and atherosclerosis-related genes' variants on long-term
recurrent hard cardiac events after a myocardial infarction.
AB - Atherosclerotic coronary artery disease (CAD) and myocardial infarction (MI) as
its most severe clinical complication remain the leading causes of mortality in
the majority of countries. Despite the progress in the treatment of MI, quite
often the patients, after the first-time MI, develop subsequently a variety of
adverse cardiovascular events. In this retrospective study we evaluated the
contribution of allelic variations in 9p21.3 locus and in 21 atherogenesis
related genes to the development of hard cardiac events in a cohort of patients
of Russian ethnicity after the first acute MI during long-term follow-up (7-10
years). Death from cardiac causes and recurrent nonfatal MI were considered as
key clinical outcomes. We have shown the association of rs1333049 and rs10757278
in 9p21.3 and MTHFR rs1801133 with recurrent unfavorable events, the latter was
observed in time-dependent manner. Multilocus analysis additionally suggested the
influence of carriage of the CRP and ENOS genes variants at the development of
subsequent adverse events after MI. The composite model built for prediction of
the individual genetic risk of postinfarction hard cardiac events included 9p21.3
rs1333049*GG and MTHFR*TT and was characterized by area under the curve (AUC) =
0.65. Our data show that 9p21.3 locus and MTHFR gene polymorphisms could
influence long-term prognosis of recurrent hard cardiac events in patients who
underwent the first MI. It is possible that addition of genotyping at such loci
to existing clinical scores could improve their predictability.
PMID- 29331482
TI - Genetic basis of hearing loss in Spanish, Hispanic and Latino populations.
AB - Hearing loss (HL) is the most common neurosensory disorder affecting humans. The
screening, prevention and treatment of HL require a better understanding of the
underlying molecular mechanisms. Genetic predisposition is one of the most common
factors that leads to HL. Most HL studies include few Spanish, Hispanic and
Latino participants, leaving a critical gap in our understanding about the
prevalence, impact, unmet health care needs, and genetic factors associated with
hearing impairment among Spanish, Hispanic and Latino populations. The few
studies which have been performed show that the gene variants commonly associated
with HL in non-Spanish and non-Hispanic populations are infrequently responsible
for hearing impairment in Spanish as well as Hispanic and Latino populations
(hereafter referred to as Hispanic). To design effective screening tools to
detect HL in Spanish and Hispanic populations, studies must be conducted to
determine the gene variants that are most commonly associated with hearing
impairment in this racial/ethnic group. In this review article, we summarize gene
variants and loci associated with HL in Spanish and Hispanic populations.
Identifying new genetic variants associated with HL in Spanish and Hispanic
populations will pave the way to develop effective screening tools and
therapeutic strategies for HL.
PMID- 29331486
TI - Prenatal exposure to acetaminophen and children's language development at 30
months.
AB - OBJECTIVE: To examine prenatal APAP exposure in relation to language development
in offspring at 30 months of age. METHOD: A population-based pregnancy cohort
study including 754 women who enrolled in the Swedish Environmental Longitudinal,
Mother and child, Asthma and allergy (SELMA) study in pregnancy week 8-13. Two
exposure measures were used: (1) maternally reported number of APAP tablets taken
between conception and enrollment; (2) APAP urinary concentration at enrollment.
Language development at 30 months was assessed by nurse's evaluation and parental
questionnaire, including the number of words the child used (<25, 25-50 and >50).
Main study outcome; parental report of use of fewer than 50 words, termed
language delay (LD). RESULTS: 59.2% of women enrolled in weeks 8-13 reported
taking APAP between conception and enrollment. APAP was measurable in all urine
samples and urinary APAP was correlated with the number of APAP taken during
pregnancy (P<0.01). Language delay was more prevalent in boys (12.6%) than girls
(4.1%) (8.5% in total). Both the number of APAP tablets and urinary APAP
concentration were associated with greater LD in girls but not in boys. The
adjusted odds ratio (OR) for LD among girls whose mothers reported >6 vs. 0 APAP
tablets was 5.92 (95% confidence interval (CI) 1.10-31.94). The OR for LD in
girls whose mothers' urinary APAP was in the highest compared to the lowest
quartile was 10.34 (95% CI 1.37-77.86). While it cannot be ruled out, our
available data do not support confounding by indication. CONCLUSIONS: Given the
prevalence of prenatal APAP use and the importance of language development, these
findings, if replicated, would suggest that pregnant women should limit their use
of this analgesic during pregnancy.
PMID- 29331487
TI - CureCuma-cationic curcuminoids with improved properties and enhanced
antimicrobial photodynamic activity.
AB - The naturally occurring photosensitizer curcumin has excellent biocompatibility,
but its antimicrobial photodynamic efficacy is limited by (i) weak adherence to
Gram(-) bacteria cell walls, (ii) low (photo-)stability and (iii) limited
solubility in water. In this study novel curcuminoids bearing cationic
substituents were prepared by different synthetic routes. The derivatives exhibit
excellent water solubility, improved photostability and low aggregation. All
novel curcuminoids showed antibacterial photodynamic effects (>3 log10 reduction
of CFU) against Escherichia coli and Staphylococcus aureus upon blue light
illumination. In contrast to natural curcumin, effective photokilling of E. coli
was possible without the addition of permeabilizing agents. Ten micromolar of the
most active compound (8) achieved a 7 log10 decrease of E. coli after light
activation with a fluence of 33.8 J/cm2, whereas S. aureus was inactivated by
more than 4 log10 at a fluence of 5.3 J/cm2. Overall the reduction in bacterial
count was at least 100-fold more effective with these new curcuminoids in
comparison to natural curcumin.
PMID- 29331488
TI - A potential utilization of end-of-life tyres as recycled carbon black in EPDM
rubber.
AB - End-of-life (EOL) tyres and their decomposition present severe environmental
concern due to their resistance to moisture, oxygen, natural degradation, etc.
Pyrolysis is considered to be the most effective and sustainable process for
recycling, due to its eco-friendly process. The current work studied the effect
of recycled carbon black (rCB), obtained from the pyrolysis of EOL tyres, on the
properties of ethylene propylene diene rubber (EPDM). The rCB was characterized
by scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and
chemical methods. rCB was incorporated solely, into a conventional EPDM
formulation and also in combination with N550 carbon black. The physico
mechanical properties of the EPDM vulcanizates, before and after aging, were
succinctly studied by SEM, TGA, Differential Scanning Calorimetry (DSC), tensile
tests and cross-link density. The average particle size of rCB was observed to be
8 um and the ash content was observed to be higher when compared to the
conventional N550 carbon black, which was evident, by the TGA and SEM-EDX
analyses. The reinforcing effect and the cross-link density of the rCB-filled
vulcanizates were found to be marginally inferior in comparison to the
conventional carbon black (N550). The morphology of the tensile- and tear
fractured surfaces were studied by SEM and it was observed that the breaking
mechanism follows the rubber chain detachment from the surface mode.
PMID- 29331489
TI - Modulation of lower extremity joint stiffness, work and power at different
walking and running speeds.
AB - Locomotion task and speed changes affect dynamic joint function. Walking and
running require different coordination patterns of lower extremity joint
mechanics. These coordination differences can result in measurable changes in
kinematic and kinetic patterns. When locomotion speed changes, the functional
role and movement strategy of each joint is altered. A deeper understanding of
joint level mechanics and functional interactions will benefit rehabilitation
programs and assistive device development. In this study, joint stiffness, joint
mechanical work and power were assessed, as they relate to dynamic function of
joints during locomotion. Ten young healthy subjects (5 males, 5 females)
participated in a treadmill walking (0.8-2.0 m/s) and running (1.8-3.8 m/s)
study. When running speed increased, the stiffness of all three joints tended to
increase. The ankle joint played a dominant role during the stance phase of
running, generating more positive work than the knee (p = .003) and hip (p =
.0001). The knee and hip joint were more dominant in walking and running swing
phase energy absorption and generation, respectively. When locomotion speeds
increased, stance phase ankle positive work, swing phase knee negative work, and
hip joint positive work tended to increase. These findings suggest that change of
locomotion speed or task results in definitive changes to lower extremity joint
level mechanics patterns.
PMID- 29331490
TI - Supervised Machine Learning for Population Genetics: A New Paradigm.
AB - As population genomic datasets grow in size, researchers are faced with the
daunting task of making sense of a flood of information. To keep pace with this
explosion of data, computational methodologies for population genetic inference
are rapidly being developed to best utilize genomic sequence data. In this review
we discuss a new paradigm that has emerged in computational population genomics:
that of supervised machine learning (ML). We review the fundamentals of ML,
discuss recent applications of supervised ML to population genetics that
outperform competing methods, and describe promising future directions in this
area. Ultimately, we argue that supervised ML is an important and underutilized
tool that has considerable potential for the world of evolutionary genomics.
PMID- 29331491
TI - Investigating the relationship between cardiac interoception and autonomic
cardiac control using a predictive coding framework.
AB - Predictive coding models, such as the 'free-energy principle' (FEP), have
recently been discussed in relation to how interoceptive (afferent visceral
feedback) signals update predictions about the state of the body, thereby driving
autonomic mediation of homeostasis. This study appealed to 'interoceptive
inference', under the FEP, to seek new insights into autonomic (dys)function and
brain-body integration by examining the relationship between cardiac
interoception and autonomic cardiac control in healthy controls and patients with
forms of orthostatic intolerance (OI); to (i) seek empirical support for
interoceptive inference and (ii) delineate if this relationship was sensitive to
increased interoceptive prediction error in OI patients during head-up tilt
(HUT)/symptom provocation. Measures of interoception and heart rate variability
(HRV) were recorded whilst supine and during HUT in healthy controls (N = 20),
postural tachycardia syndrome (PoTS, N = 20) and vasovagal syncope (VVS, N = 20)
patients. Compared to controls, interoceptive accuracy was reduced in both OI
groups. Healthy controls' interoceptive sensibility positively correlated with
HRV whilst supine. Conversely, both OI groups' interoceptive awareness negatively
correlated with HRV during HUT. Our pilot study offers initial support for
interoceptive inference and suggests OI cohorts share a central pathophysiology
underlying interoceptive deficits expressed across distinct cardiovascular
autonomic pathophysiology. From a predictive coding perspective, OI patients'
data indicates a failure to attenuate/modulate ascending interoceptive prediction
errors, reinforced by the concomitant failure to engage autonomic reflexes during
HUT. Our findings offer a potential framework for conceptualising how the human
nervous system maintains homeostasis and how both central and autonomic processes
are ultimately implicated in dysautonomia.
PMID- 29331492
TI - Prognostic Value of the Expression of DNA Repair-Related Biomarkers Mediated by
Alcohol in Gastric Cancer Patients.
AB - Alcohol consumption likely induces gastric carcinogenesis through deregulation of
RNA polymerase (Pol) III genes and oxidative damage. Transcription factor IIB
related factor 1 (BRF1) overexpression alleviates RNA Pol III transcription
inhibition through breast cancer susceptibility gene 1 (BRCA1). Myeloperoxidase
(MPO) involvement in cancer is induced by alcohol-mediated oxidative damage.
BRCA1/2 and MPO play key roles in DNA repair. BRCA1 and BRCA2 exert different
roles in homologous recombination repair. By using human gastric cancer (GC)
biopsies, we investigated the prognostic value of these proteins upon alcohol
induction. In total, high expression of BRF1 (P = 0.010) and positive cell
infiltration of MPO (P = 0.004) in tumor tissues as well as positive expression
of BRCA1 (P < 0.001) in para-tumor tissues were more frequent in GC patients with
hazardous or harmful alcohol consumption habits. BRF1 (P = 0.021), BRCA2 (P <
0.001), and MPO (P = 0.039) were independent prognostic factors for disease-free
survival. BRCA1 (P = 0.005) and BRCA2 (P < 0.001) also were identified as
independent prognostic factors for overall survival. Furthermore, BRCA2 was an
independent unfavorable prognostic factor for disease-free survival and overall
survival (P < 0.001) in GC patients who underwent platinum-based adjuvant
chemotherapy. BRF1, BRCA1/2, and MPO are DNA repair-related biomarkers, induced
by alcohol with prognostic value in GC patients.
PMID- 29331493
TI - Hip Dislocations in the Emergency Department: A Review of Reduction Techniques.
AB - BACKGROUND: Hip dislocations are a common presentation in the Emergency
Department (ED) and require urgent reduction to reduce the risk of avascular
necrosis. Over 90% of all dislocations can successfully be reduced in the ED and
there is evidence that cases awaiting operative reduction result in significant
delays. DISCUSSION: While there is limited data comparing specific techniques,
the individual success rates of most maneuvers range from 60-90%. Additionally,
each technique has distinct advantages and limitations associated with its use.
CONCLUSIONS: It is important for Emergency Physicians to be familiar with several
different reduction techniques in case the initial reduction attempt is
unsuccessful or patient characteristics limit the use of certain maneuvers. This
article reviews a number of reduction techniques for hip dislocations, variations
on these techniques, and advantages and disadvantages for each approach.
PMID- 29331494
TI - A Novel Difficult-Airway Prediction Tool for Emergency Airway Management:
Validation of the HEAVEN Criteria in a Large Air Medical Cohort.
AB - BACKGROUND: Difficult-airway prediction tools help identify optimal airway
techniques, but were derived in elective surgery patients and may not be
applicable to emergency rapid sequence intubation (RSI). The HEAVEN criteria
(Hypoxemia, Extremes of size, Anatomic abnormalities, Vomit/blood/fluid,
Exsanguination, Neck mobility issues) may be more relevant to emergency RSI
patients. OBJECTIVE: To validate the HEAVEN criteria for difficult-airway
prediction in emergency RSI using a large air medical cohort. METHODS: This was a
retrospective analysis using a large air medical airway registry using data from
160 bases over a 1-year period. Standard test characteristics (sensitivity,
specificity, positive predictive value, negative predictive value [NPV]) for the
HEAVEN criteria were calculated for overall intubation success, first-attempt
success, and first-attempt success without desaturation. In addition,
multivariable logistic regression was used to quantify the independent
association between each of the HEAVEN criteria, as well as the total number of
criteria present and intubation success after adjusting for age, gender, and
clinical category (burn, medical, trauma, nontraumatic shock). RESULTS: A total
of 2419 patients undergoing air medical RSI were included. Excellent NPV was
observed (97% for each of the HEAVEN criteria except "Exsanguination," which had
an NPV of 87% but specificity of 99%). First-attempt success was lower for each
of the HEAVEN criteria, with an inverse relationship observed between total
HEAVEN criteria and intubation success (first-attempt success with no criteria =
94% and with 5 + criteria = 43%). Multivariable logistic regression revealed
independent associations between each of the HEAVEN criteria, as well as total
number of criteria and intubation success. CONCLUSIONS: The HEAVEN criteria seem
to be a useful tool to predict difficult airways in emergency RSI.
PMID- 29331495
TI - Role of BCL2L10 in regulating buffalo (Bubalus bubalis) oocyte maturation.
AB - It has been reported that BCL2L10 is abundantly and specifically expressed in
adult human and mouse oocytes and played a very important role in oocytes
maturation and early embryonic development. This study is to investigate the
expression pattern of BCL2L10 in buffalo ovaries and its effect on the in vitro
maturation of buffalo oocytes, so as to dissect mechanism of oocytes maturation
and provide theoretical guidance for improvement of the in vitro maturation of
buffalo oocytes. The results showed that BCL2L10 gene was enriched in ovary and
the expression of BCL2L10 was oocyte specific and up-regulated during oocyte
maturation. BCL2L10 protein and mRNA were detectable in buffalo early embryos,
upregulated at 2-cell to 8-cell stages and down-regulated in the later stages.
Knockdown of BCL2L10 by RNA interference resulted in a significant decrease in
the maturation rate (33.5%) and cleavage rate (37.52%) of buffalo oocytes coupled
with up-regulation of apoptosis-related gene Caspase-9. We concluded that BCL2L10
is a candidate associated with buffalo oocyte maturation.
PMID- 29331496
TI - Maternal betaine supplementation attenuates glucocorticoid-induced hepatic lipid
accumulation through epigenetic modification in adult offspring rats.
AB - There are lots of reports about alleviation of NAFLD by dietary supplements of
betaine. However, it remains unclear whether maternal betaine supplementation can
also ameliorate NAFLD in offspring. Hence, twenty pregnant rats were fed with a
basal diet with or without betaine (1%), and then the female offspring rats were
raised at 3 months of age followed by 3 weeks of physiological saline or
dexamethasone in a dose of 0.1 mg/kg body mass every day via intraperitoneal
injection. In this study, maternal betaine supplementation significantly (P<.05)
reduced the increase of hepatic triglycerides concentration in dexamethasone
induced rats, which is associated with the expression of hepatic lipogenic genes
(ACC1, FASN and SCD1). Moreover, the hypomethylation of lipogenic genes in
dexamethasone-induced rats were reserved by prenatal betaine exposure.
Furthermore, the increase of hepatic GR or SP1 content in dexamethasone-injected
rats were significantly decreased (P<.05), which were in line with the binding of
GR or SP1 to lipogenic genes, in betaine -exposed rats. Together, these results
suggest that maternal betaine supplementation attenuates dexamethason-induced
fatty liver in the female adult offspring rats, which may be attributed to DNA
methylation and GR or SP1-mediated the regulation of lipogenic genes.
PMID- 29331497
TI - Dietary antioxidant micronutrients alter mucosal inflammatory risk in a murine
model of genetic and microbial susceptibility.
AB - Inflammatory bowel diseases (IBD) are caused by the convergence of microbial,
environmental, and genetic factors. Diet significantly alters these interactions
by affecting both the host and microbiome. Using a mucosal inflammatory model
that resembles the human condition of ileal pouchitis, we investigated the
effects of Control (CONT) or Antioxidant (AOX) diet, containing pharmacologically
relevant levels of 4 micronutrients, on disease risk in wild-type and IL-10-/-
animals following surgical self-filling (SF) ileal blind loop placement. Although
no differences were found in body weight change or survival, IL-10-/- CONT
animals had significantly larger lymphoid organs compared with IL-10-/- AOX or
with WT. SF loops from IL-10-/- CONT loop mucosa demonstrated histological
inflammation, characterized by goblet cell depletion, increased mucosal
myeloperoxidase (MPO), and elevated IFNgamma, TNFalpha, and IL-17alpha gene
expression, which AOX attenuated. AOX elevated luminal IgA in IL-10-/- animals,
but not significantly in WT. In IL-10-/- animals, AOX significantly decreased the
percentage of CD4 + T-bet and CD4 + RORgamma T-cells compared with CONT, with no
changes in CD4 + Foxp3+ Treg cells. 16S rRNA gene sequencing demonstrated AOX
increased microbial alpha diversity compared with CONT in both genotypes.
Notably, colonizing germ-free IL-10-/- hosts with CONT bacterial communities, but
not AOX, recapitulated the inflammatory phenotype. Collectively, these findings
highlight that common dietary antioxidant micronutrients reshape the gut
microbial community to mitigate intestinal inflammatory profiles in genetically
susceptible hosts. Insights into the dietary-immune-microbial nexus may improve
understanding for recurrent inflammatory episodes in susceptible patient
populations and opportunities for practical therapeutics to restore immune and
microbial homeostasis.
PMID- 29331498
TI - Identification of neural transcription factors required for the differentiation
of three neuronal subtypes in the sea urchin embryo.
AB - Correct patterning of the nervous system is essential for an organism's survival
and complex behavior. Embryologists have used the sea urchin as a model for
decades, but our understanding of sea urchin nervous system patterning is
incomplete. Previous histochemical studies identified multiple neurotransmitters
in the pluteus larvae of several sea urchin species. However, little is known
about how, where and when neural subtypes are differentially specified during
development. Here, we examine the molecular mechanisms of neuronal subtype
specification in 3 distinct neural subtypes in the Lytechinus variegatus larva.
We show that these subtypes are specified through Delta/Notch signaling and
identify a different transcription factor required for the development of each
neural subtype. Our results show achaete-scute and neurogenin are proneural for
the serotonergic neurons of the apical organ and cholinergic neurons of the
ciliary band, respectively. We also show that orthopedia is not proneural but is
necessary for the differentiation of the cholinergic/catecholaminergic postoral
neurons. Interestingly, these transcription factors are used similarly during
vertebrate neurogenesis. We believe this study is a starting point for building a
neural gene regulatory network in the sea urchin and for finding conserved
deuterostome neurogenic mechanisms.
PMID- 29331499
TI - Hspb7 is a cardioprotective chaperone facilitating sarcomeric proteostasis.
AB - Small heat shock proteins are chaperones with variable mechanisms of action. The
function of cardiac family member Hspb7 is unknown, despite being identified
through GWAS as a potential cardiomyopathy risk gene. We discovered that
zebrafish hspb7 mutants display mild focal cardiac fibrosis and sarcomeric
abnormalities. Significant mortality was observed in adult hspb7 mutants
subjected to exercise stress, demonstrating a genetic and environmental
interaction that determines disease outcome. We identified large sarcomeric
proteins FilaminC and Titin as Hspb7 binding partners in cardiac cells. Damaged
FilaminC undergoes autophagic processing to maintain sarcomeric homeostasis. Loss
of Hspb7 in zebrafish or human cardiomyocytes stimulated autophagic pathways and
expression of the sister gene encoding Hspb5. Inhibiting autophagy caused
FilaminC aggregation in HSPB7 mutant human cardiomyocytes and developmental
cardiomyopathy in hspb7 mutant zebrafish embryos. These studies highlight the
importance of damage-processing networks in cardiomyocytes, and a previously
unrecognized role in this context for Hspb7.
PMID- 29331500
TI - Peripheral modulation of the endocannabinoid system in metabolic disease.
AB - Dysfunction of the endocannabinoid system (ECS) has been identified in metabolic
disease. Cannabinoid receptor 1 (CB1) is abundantly expressed in the brain but
also expressed in the periphery. Cannabinoid receptor 2 (CB2) is more abundant in
the periphery, including the immune cells. In obesity, global antagonism of
overexpressed CB1 reduces bodyweight but leads to centrally mediated adverse
psychological outcomes. Emerging research in isolated cultured cells or tissues
has demonstrated that targeting the endocannabinoid system in the periphery
alleviates the pathologies associated with metabolic disease. Further, peripheral
specific cannabinoid ligands can reverse aspects of the metabolic phenotype. This
Keynote review will focus on current research on the functionality of peripheral
modulation of the ECS for the treatment of obesity.
PMID- 29331502
TI - Contrast-induced nephropathy - an entity to bear in mind and to prevent: A
nephrological perspective.
PMID- 29331501
TI - Incorporating upper motor neuron health in ALS drug discovery.
AB - Amyotrophic lateral sclerosis (ALS) is a complex disease, that affects the motor
neuron circuitry. After consecutive failures in clinical trials for the past 20
years, edaravone was recently approved as the second drug for ALS. This generated
excitement in the field revealed the need to improve preclinical assays for
continued success. Here, we focus on the importance and relevance of upper motor
neuron (UMN) pathology in ALS, and discuss how incorporation of UMN survival in
preclinical assays will improve inclusion criteria for clinical trials and
expedite the drug discovery effort in ALS and related motor neuron diseases.
PMID- 29331503
TI - Clinical scores in acute coronary syndrome: When and why should we use them?
PMID- 29331504
TI - A Systematic Review of Health Care Provider-Perceived Barriers and Facilitators
to Routine HIV Testing in Primary Care Settings in the Southeastern United
States.
AB - Despite efforts to improve HIV screening and testing, many primary care settings
do not follow established guidelines. The purpose of our systematic review was to
describe health care providers' perceived barriers and facilitators to testing
for HIV at poorly used/novel testing sites in the southeastern United States.
PubMed, CINAHL, and Embase databases were searched for peer-reviewed studies of
providers' perceived barriers and facilitators to routine HIV testing from
January 2016 to April 2017 according to the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses (PRISMA) statement. Of 708 papers retrieved,
12 met inclusion criteria and were analyzed. Barriers to HIV testing in primary
care existed at the societal, organizational, and individual levels. Providers
need continuing sexual health education, including HIV and federal guideline
updates, and students should have clinical experiences to supplement knowledge
about sexual health. Clinic protocols should be updated to meet current policy
guidelines.
PMID- 29331505
TI - Successful Treatment of Anti-angiotensin II Type 1 Receptor Antibody-Associated
Rejection in Kidney Transplantation: A Case Report.
AB - Angiotensin II type 1 receptor (AT1R) antibody, a non-HLA antibody, has been
found to have a detrimental effect on kidney allografts. Similarly to HLA
antibodies, recipients who have AT1R antibodies are at risk for allograft
rejection and poor long-term graft outcome. Besides mediating allograft
rejections via direct effects on endothelial and vascular smooth muscle without
complement activation, AT1R antibodies may lead to accelerated hypertension via
the renin-angiotensin pathway. There has been no definite level of AT1R antibody
that predicts allograft rejection. Because of a low incidence of AT1R antibody
associated rejection, there are few reports on specific treatment. The results of
conventional treatment, which aims to remove these pathologic antibodies
similarly to the treatment of HLA antibody-associated rejection, have been
unsatisfactory. Some studies recommend using angiotensin receptor blocker to
attenuate the adverse effects of AT1R antibody on kidney allograft. Herein we
present a kidney transplant recipient with AT1R antibody-associated refractory
allograft rejection who was successfully treated with the use of steroid,
plasmapheresis, intravenous immunoglobulin, and rituximab.
PMID- 29331506
TI - Hepatocyte estrogen receptor alpha mediates estrogen action to promote reverse
cholesterol transport during Western-type diet feeding.
AB - OBJECTIVE: Hepatocyte deletion of estrogen receptor alpha (LKO-ERalpha) worsens
fatty liver, dyslipidemia, and insulin resistance in high-fat diet fed female
mice. However, whether or not hepatocyte ERalpha regulates reverse cholesterol
transport (RCT) in mice has not yet been reported. METHODS AND RESULTS: Using LKO
ERalpha mice and wild-type (WT) littermates fed a Western-type diet, we found
that deletion of hepatocyte ERalpha impaired in vivo RCT measured by the removal
of 3H-cholesterol from macrophages to the liver, and subsequently to feces, in
female mice but not in male mice. Deletion of hepatocyte ERalpha decreased the
capacity of isolated HDL to efflux cholesterol from macrophages and reduced the
ability of isolated hepatocytes to accept cholesterol from HDL ex vivo in both
sexes. However, only in female mice, LKO-ERalpha increased serum cholesterol
levels and increased HDL particle sizes. Deletion of hepatocyte ERalpha increased
adiposity and worsened insulin resistance to a greater degree in female than male
mice. All of the changes lead to a 5.6-fold increase in the size of early
atherosclerotic lesions in female LKO-ERalpha mice compared to WT controls.
CONCLUSIONS: Estrogen signaling through hepatocyte ERalpha plays an important
role in RCT and is protective against lipid retention in the artery wall during
early stages of atherosclerosis in female mice fed a Western-type diet.
PMID- 29331508
TI - Compartmentalized crosstalk of CFTR and TMEM16A (ANO1) through EPAC1 and ADCY1.
AB - Airway epithelial cells express both Ca2+ activated TMEM16A/ANO1 and cAMP
activated CFTR anion channels. Previous work suggested a significant crosstalk of
intracellular Ca2+ and cAMP signaling pathways, leading to activation of both
chloride channels. We demonstrate that in airway epithelial cells, stimulation of
purinergic or muscarinic G-protein coupled receptors (GPCRs) activates TMEM16A
and CFTR. Additional expression of Gq/11 and phospholipase C coupled GPCRs
strongly enhanced the crosstalk between Ca2+- and cAMP-dependent signaling.
Knockdown of endogenous GRCRs attenuated crosstalk and functional coupling
between TMEM16A and CFTR. The number of receptors did not affect expression or
membrane localization of TMEM16A or CFTR, but controlled assembly of the local
signalosome. GPCRs translocate Ca2+-sensitive adenylate cyclase type 1 (ADCY1)
and exchange protein directly activated by cAMP (EPAC1) to particular plasma
membrane domains containing GPCRs, CFTR and TMEM16A, thereby producing
compartmentalized Ca2+ and cAMP signals and significant crosstalk. While
biosynthesis and membrane trafficking of CFTR requires a functional Golgi
apparatus, maturation and membrane trafficking of TMEM16A may occur independent
of the Golgi. Because Ca2+ activated TMEM16A currents are only transient,
continuous Cl- secretion by airway epithelial cells requires CFTR. The present
data also explain why receptor-dependent activation of TMEM16A is more efficient
than direct stimulation by Ca2+.
PMID- 29331509
TI - Selenolanthionine is the major water-soluble selenium compound in the selenium
tolerant plant Cardamine violifolia.
AB - BACKGROUND: Selenium hyperaccumulation in plants often involves the synthesis of
non-proteinaceous methylated selenoamino acids serving for the elimination of
excess selenium from plant metabolism to protect plant homeostasis. METHODS: Our
study aimed at the identification of the main selenium species of the selenium
hyperaccumulator plant Cardamine violifolia (Brassicaceae) that grows in the wild
in the seleniferous region of Enshi, China. A sample of this plant (3.7 g Se kg-1
d.w.) was prepared with several extraction methods and the extracted selenium
species were identified and quantified with liquid chromatography mass
spectrometry set-ups. RESULTS: The Cardamine violifolia sample did not contain in
considerable amount any of the organic selenium species that are often formed in
hyperaccumulator plants; the inorganic selenium content (mostly as elemental
selenium) accounted only for <20% of total Se. The most abundant selenium
compound, accounting for about 40% of total Se was proved to be
selenolanthionine, a selenium species that has never been unambiguously
identified before from any selenium containing sample. The identification process
was completed with chemical synthesis too. The molar ratio of
lanthionine:selenolanthionine in the water extract was ca. 1:8. CONCLUSIONS:
Finding selenolanthionine as the main organic selenium species in a plant
possibly unearths a new way of selenium tolerance. This article is part of a
Special Issue entitled Selenium research in biochemistry and biophysics - 200
year anniversary issue, edited by Dr. Elias Arner and Dr. Regina Brigelius-Flohe.
PMID- 29331510
TI - Effects of sub-minimum inhibitory concentrations of lemon essential oil on the
acid tolerance and biofilm formation of Streptococcus mutans.
AB - OBJECTIVES: Lemon essential oil (LEO) is a kind of secondary metabolite from
lemon peels and has been found to inhibit cariogenic bacteria for decades.
However, its effects on main cariogenic virulence factors are rarely reported.
The present study aimed to investigate the effects of sub-minimum inhibitory
concentrations (sub-MICs) of LEO on the acid tolerance and biofilm formation of
Streptococcus mutans (S. mutans) and preliminarily reveal the possible underlying
mechanisms. DESIGNS: Effects of LEO on the acid tolerance and biofilm formation
of S. mutans were investigated by the broth dilution method and crystal violet
staining method respectively. The expression of luxS, srtA and spaP gene was also
determined to explore the underlying mechanism. In addition, Tea polyphenols
(TP), a major natural inhibitor of cariogenic virulence factors, and limonene
(LIM), the major component of LEO, were selected as comparisons to evaluate the
effects of LEO. RESULTS: Sub-MICs of LEO, LIM and TP exhibited a dose-dependent
inhibition of growth of S. mutans at pH ranging from 4.0 to 7.0. The formation of
S. mutans biofilm was remarkably inhibited and the inhibitory rates of LEO, LIM
and TP were 97.87%, 94.88% and 96.01% respectively at 1/2 MIC. Similarly, a down
regulation was observed in the expression of luxS, srtA and spaP gene at sub-MIC
levels. CONCLUSIONS: Effects of LEO were similar or slightly stronger than LIM
and TP, suggesting that LEO might represent a novel, natural anticarious agent
that inhibited the specific genes associated with bacterial acid tolerance and
biofilm formation without necessarily affecting the growth of oral bacteria.
PMID- 29331507
TI - Adropin: An endocrine link between the biological clock and cholesterol
homeostasis.
AB - OBJECTIVE: Identify determinants of plasma adropin concentrations, a secreted
peptide translated from the Energy Homeostasis Associated (ENHO) gene linked to
metabolic control and vascular function. METHODS: Associations between plasma
adropin concentrations, demographics (sex, age, BMI) and circulating biomarkers
of lipid and glucose metabolism were assessed in plasma obtained after an
overnight fast in humans. The regulation of adropin expression was then assessed
in silico, in cultured human cells, and in animal models. RESULTS: In humans,
plasma adropin concentrations are inversely related to atherogenic LDL
cholesterol (LDL-C) levels in men (n = 349), but not in women (n = 401). Analysis
of hepatic Enho expression in male mice suggests control by the biological clock.
Expression is rhythmic, peaking during maximal food consumption in the dark
correlating with transcriptional activation by RORalpha/gamma. The nadir in the
light phase coincides with the rest phase and repression by Rev-erb. Plasma
adropin concentrations in nonhuman primates (rhesus monkeys) also exhibit peaks
coinciding with feeding times (07:00 h, 15:00 h). The ROR inverse agonists SR1001
and the 7-oxygenated sterols 7-beta-hydroxysterol and 7-ketocholesterol, or the
Rev-erb agonist SR9009, suppress ENHO expression in cultured human HepG2 cells.
Consumption of high-cholesterol diets suppress expression of the adropin
transcript in mouse liver. However, adropin over expression does not prevent
hypercholesterolemia resulting from a high cholesterol diet and/or LDL receptor
mutations. CONCLUSIONS: In humans, associations between plasma adropin
concentrations and LDL-C suggest a link with hepatic lipid metabolism. Mouse
studies suggest that the relationship between adropin and cholesterol metabolism
is unidirectional, and predominantly involves suppression of adropin expression
by cholesterol and 7-oxygenated sterols. Sensing of fatty acids, cholesterol and
oxysterols by the RORalpha/gamma ligand-binding domain suggests a plausible
functional link between adropin expression and cellular lipid metabolism.
Furthermore, the nuclear receptors RORalpha/gamma and Rev-erb may couple adropin
synthesis with circadian rhythms in carbohydrate and lipid metabolism.
PMID- 29331512
TI - A format for reviewing a research paper.
PMID- 29331511
TI - Maresin 1 regulates autophagy and inflammation in human periodontal ligament
cells through glycogen synthase kinase-3beta/beta-catenin pathway under
inflammatory conditions.
AB - OBJECTIVE: Accumulating lines of evidence suggest that maresin 1 (MaR-1) exerts
anti-inflammatory effects in many cell types and plays beneficial roles in
inflammatory disease, such as peritonitis and colitis. Moreover, it has been
demonstrated that MaR-1 play protective roles against localized aggressive
periodontitis. However, the function and mechanism of MaR-1 in human periodontal
ligament cells (PDL) cells from periodontitis are poorly understood. The present
study aimed to clarify the effects and molecular mechanism of MaR-1 in PDL cell
survival and inflammation. METHODS: PDL cells were isolated from the middle third
of the root surface of premolars from four healthy humans; MTT assay and cell
death detection ELISA assay were used to detect cell survival and apoptosis;
Inflammatory cytokines level was measured by ELISA assay; RT-PCR and western blot
was used to measure the mRNA and protein expression in this study. RESULTS: Here
we found that MaR-1 treatment markedly promotes survival and inhibits apoptosis
in PDL cell treated by LPS. MaR-1 treatment strikingly suppressed the production
of LPS-induced pro-inflammatory cytokines IL-6, IL-8, TNF-alpha and IL-1beta. MaR
1 also promotes autophagy by increasing the ratio of LC3II/LC3I, the level of
beclin-1 and reduced the expression of p62 in LPS treated PDL cells, which is
beneficial to cell survival. Moreover, the results showed that MaR-1-mediated
autophagy is dependent on the glycogen synthase kinase-3beta(GSK-3beta)/beta
catenin signal pathway. The inhibitor of autophagy 3-MA and the inhibitor of the
GSK-3beta/beta-catenin signal pathway LiCL both reverse the effects of MaR-1 on
LPS-treated PDL cell survival and inflammation. CONCLUSION: MaR-1 promotes cell
survival and alleviates cell inflammation by activating GSK-3beta/beta-catenin
dependent autophagy. These results provide new insights into the mechanism of
chronic periodontitis.
PMID- 29331513
TI - Multiple myeloma and a mischievous pacemaker: A teaching case involving
irradiation of a cardiovascular implantable electronic device.
PMID- 29331514
TI - Employment of proteomic and immunological based methods for the identification of
catalase as novel allergen from banana.
AB - : Diagnostic reagents based on food allergen extracts often lack sufficient
sensitivity. The introduction of well characterized food allergens in molecular
allergy diagnosis has been recognized as valid approach to circumvent
unstandardized allergen extracts. Banana fruit (Musa acuminata) is a well
established allergen source which besides six characterized allergens, contains
unidentified IgE reactive proteins whose clinical relevance remains undefined. By
employment of a combinatorial peptide ligand library (CPLL) methodology with 2-D
PAGE, mass spectrometric and 2-D immunoblot analysis, a novel allergen from
banana fruit was detected in banana as catalase. A recombinant homologue of
natural catalase was produced, isolated and biochemically characterized. The
recombinant protein showed IgE reactivity in 7 out of 13 tested patients with
suspected allergy to banana in immunoblot. Novel banana fruit allergens should be
added as components to allergen-microarrays for the diagnosis and the monitoring
of banana allergy. SIGNIFICANCE: By employment of CPLL methodology with 2-D PAGE,
mass spectrometric and 2-D immunoblot analysis catalase from banana fruit is
identified as a novel allergen, with proposed designation as Mus a 7. IgE
reactive recombinant Mus a 7 was produced and should be included in a component
resolved allergy diagnosis.
PMID- 29331516
TI - Simultaneous saccharification and aerobic fermentation of high titer cellulosic
citric acid by filamentous fungus Aspergillus niger.
AB - Simultaneous saccharification and fermentation (SSF) is the most efficient
operation in biorefining conversion, but aerobic SSF under high solids loading
significantly faces the serious oxygen transfer limitation. This study took the
first insight into an aerobic SSF by high oxygen demanding filamentous fungi in
highly viscous lignocellulose hydrolysate. The results show that oxygen
requirement in the aerobic SSF by Aspergillus niger was well satisfied for
production of cellulosic citric acid. The record high citric acid titer of 136.3
g/L and the overall conversion yield of 74.9% of cellulose were obtained by the
aerobic SSF. The advantage of SSF to the separate hydrolysis and fermentation
(SHF) on citric acid fermentation was compared based on the rigorous Aspen Plus
modeling. The techno-economic analysis indicates that the minimum citric acid
selling price (MCSP) of $0.603 per kilogram by SSF was highly competitive with
the commercial citric acid from starch feedstock.
PMID- 29331517
TI - Tofu whey wastewater is a promising basal medium for microalgae culture.
AB - Tofu whey wastewater (TWW) is an abundant, nutrient riched and safety wastewater
and is regarded as an excellent alternative medium in fermentation. In this
study, the feasibility of algal cultivation using TWW as the basal medium was
investigated. Results indicated that through simple pH adjustment, TWW presented
a better culture performance at autotrophic, heterotrophic, and mixotrophic modes
compared with that of regular green algae medium, BG-11. The biomass
productivities of Chlorella pyrenoidosa at each trophic mode were 4.76, 1.97, and
2.08 times higher than that cultured in BG-11 medium, respectively. Although a
comparative or even lower lipid and protein content was obtained, much higher
lipid and protein productivities were obtained in TWW compared to that of BG-11.
The algal biomass accumulated in TWW can be used to produce high-value products.
Therefore, TWW is a better alternative medium for efficient algal culture.
PMID- 29331518
TI - Microwave-assisted ionic liquid-mediated rapid catalytic conversion of non-edible
lignocellulosic Sunn hemp fibres to biofuels.
AB - Sunn hemp fibre - a cellulose-rich crystalline non-food energy crop, containing
75.6% cellulose, 10.05% hemicellulose, 10.32% lignin, with high crystallinity
(80.17%) and degree of polymerization (650) - is identified as a new non-food
substrate for lignocellulosic biofuel production. Microwave irradiation is
employed to rapidly rupture the cellulose's glycosidic bonds and enhance glucose
yield to 78.7% at 160 degrees C in only 46 min. The reactants - long-chain
cellulose, ionic liquid, transition metal catalyst, and water - form a polar
supramolecular complex that rotates under the microwave's alternating polarity
and rapidly dissipates the electromagnetic energy through molecular collisions,
thus accelerating glycosidic bond breakage. In 46 min, 1 kg of Sunn hemp fibres
containing 756 g of cellulose produces 595 g of glucose at 160 degrees C, and
203 g of hydroxymethyl furfural (furanic biofuel precursor) at 180 degrees C.
Yeast mediated glucose fermentation produces 75.6% bioethanol yield at 30
degrees C, and the ionic liquid is recycled for cost-effectiveness.
PMID- 29331515
TI - MHC class I loaded ligands from breast cancer cell lines: A potential HLA-I-typed
antigen collection.
AB - : To build a catalog of peptides presented by breast cancer cells, we undertook
systematic MHC class I immunoprecipitation followed by elution of MHC class I
loaded peptides in breast cancer cells. We determined the sequence of 3196 MHC
class I ligands representing 1921 proteins from a panel of 20 breast cancer cell
lines. After removing duplicate peptides, i.e., the same peptide eluted from more
than one cell line, the total number of unique peptides was 2740. Of the unique
peptides eluted, more than 1750 had been previously identified, and of these,
sixteen have been shown to be immunogenic. Importantly, half of these immunogenic
peptides were shared between different breast cancer cell lines. MHC class I
binding probability was used to plot the distribution of the eluted peptides in
accordance with the binding score for each breast cancer cell line. We also
determined that the tested breast cancer cells presented 89 mutation-containing
peptides and peptides derived from aberrantly translated genes, 7 of which were
shared between four or two different cell lines. Overall, the high throughput
identification of MHC class I-loaded peptides is an effective strategy for
systematic characterization of cancer peptides, and could be employed for design
of multi-peptide anticancer vaccines. SIGNIFICANCE: By employing proteomic
analyses of eluted peptides from breast cancer cells, the current study has built
an initial HLA-I-typed antigen collection for breast cancer research. It was also
determined that immunogenic epitopes can be identified using established cell
lines and that shared immunogenic peptides can be found in different cancer types
such as breast cancer and leukemia. Importantly, out of 3196 eluted peptides that
included duplicate peptides in different cells 89 peptides either contained
mutation in their sequence or were derived from aberrant translation suggesting
that mutation-containing epitopes are on the order of 2-3% in breast cancer
cells. Finally, our results suggest that interfering with MHC class I function is
one of the mechanisms of how tumor cells escape immune system attack.
PMID- 29331519
TI - Understanding and misunderstanding randomized controlled trials.
AB - Randomized Controlled Trials (RCTs) are increasingly popular in the social
sciences, not only in medicine. We argue that the lay public, and sometimes
researchers, put too much trust in RCTs over other methods of investigation.
Contrary to frequent claims in the applied literature, randomization does not
equalize everything other than the treatment in the treatment and control groups,
it does not automatically deliver a precise estimate of the average treatment
effect (ATE), and it does not relieve us of the need to think about (observed or
unobserved) covariates. Finding out whether an estimate was generated by chance
is more difficult than commonly believed. At best, an RCT yields an unbiased
estimate, but this property is of limited practical value. Even then, estimates
apply only to the sample selected for the trial, often no more than a convenience
sample, and justification is required to extend the results to other groups,
including any population to which the trial sample belongs, or to any individual,
including an individual in the trial. Demanding 'external validity' is unhelpful
because it expects too much of an RCT while undervaluing its potential
contribution. RCTs do indeed require minimal assumptions and can operate with
little prior knowledge. This is an advantage when persuading distrustful
audiences, but it is a disadvantage for cumulative scientific progress, where
prior knowledge should be built upon, not discarded. RCTs can play a role in
building scientific knowledge and useful predictions but they can only do so as
part of a cumulative program, combining with other methods, including conceptual
and theoretical development, to discover not 'what works', but 'why things work'.
PMID- 29331520
TI - Vitamin C attenuates biochemical and genotoxic damage in common carp (Cyprinus
carpio) upon joint exposure to combined toxic doses of fipronil and buprofezin
insecticides.
AB - In the present study, potential protective role of Vitamin C (l-ascorbic acid)
was investigated in aquaria acclimated common carp (Cyprinus carpio) following
exposure for 96 h to combined toxic doses of fipronil (FP) and buprofezin (BPFN)
insecticides in combination (FP: 200 MUg/L; 4.57 * 10-7 mol/L and BPFN: 50 mg/L;
1.64 * 10-4 mol/L). At end of 96 h exposure, fish were supplemented with low (25
mg/L) and high (50 mg/L) doses of Vitamin C, added once daily to aquaria water
for continuous three weeks. Appropriate control groups were run in parallel. Fish
behavior was monitored throughout for signs of toxicity. At completion of
experiments, liver, kidney, brain and gills were excised for toxicity assessment
and possible remediation by the Vitamin C through biochemical determination of
reactive oxygen species (ROS), thiobarbituric acid reactive substances or TBARS,
reduced glutathione (GSH) and total protein content, levels of catalase (CAT),
superoxide dismutase (SOD) and peroxidase (POD), and the Comet assay.
Hepatosomatic index (HSI), condition factor (CF), survival rate (SR), and
combination index (CI) were also determined. Data were compared statistically at
p < 0.05. Results showed significant behavioral and biochemical alterations, and
DNA damage in the fish group exposed to FP and BPFN in combination. In fish
groups supplemented with Vitamin C following FP and BPFN treatment, significant
alleviation in tissue damage and toxic effects was represented by substantial
decreases in ROS and TBARS production (p < 0.001), along with a concomitant
significant increase in the survival rate, GSH and total protein content, HSI,
CF, and activities of SOD, CAT and POD enzymes (p < 0.001). Mean tail length of
comet and percent tail DNA decreased significantly (p < 0.001), which indicated
amelioration of DNA damage. The study concludes that Vitamin C is an effective
remedial treatment against FP and BPFN-induced damage in exposed fish.
PMID- 29331521
TI - Increased transcript levels and kinetic function of pyruvate kinase during severe
dehydration in aestivating African clawed frogs, Xenopus laevis.
AB - The African clawed frog, Xenopus laevis, can withstand extremely arid conditions
through aestivation, resulting in dehydration and urea accumulation. Aestivating
X. laevis reduce their metabolic rate, and rely on anaerobic glycolysis to meet
reduced ATP demands. The present study investigated how severe dehydration
affected the transcript levels, kinetic profile, and phosphorylation state of the
key glycolytic enzyme pyruvate kinase (PK) in the liver and skeletal muscle of X.
laevis. Compared to control frogs, severely dehydrated frogs showed an increase
in the transcript abundance of both liver and muscle isoforms of PK. While the
kinetics of muscle PK did not differ between dehydrated and control frogs, PK
from the liver of dehydrated frogs had a lower Km for phosphoenolpyruvate (PEP)
(38%), a lower Ka for fructose-1,6-bisphosphate (F1,6P2) (32%), and a greater
activation of PK via F1,6P2 (1.56-fold). PK from dehydrated frogs also had a
lower phosphorylation-state (25%) in comparison to the enzyme from control frogs
in the liver. Experimental manipulation of the phosphorylation-state of liver PK
taken from control frogs by endogenous protein phosphatases resulted in decreased
phosphorylation, and a similar kinetic profile as seen in dehydrated frogs. The
physiological consequence of dehydration-induced PK modification appears to
adjust PK function to remain active during a metabolically depressed state. This
study provides evidence for the maintenance of PK activity through elevated mRNA
levels and a dephosphorylation event which activates frog liver PK in the
dehydrated state in order to facilitate the production of ATP via anaerobic
glycolysis.
PMID- 29331523
TI - Negative Evidence of Direct Differentiation from Bone-Marrow Cells to
Keratinocytes in Normal and Wounded Skin Using Keratin 5-Specific Reporter Mice.
PMID- 29331522
TI - Nanos3 not nanos1 and nanos2 is a germ cell marker gene in large yellow croaker
during embryogenesis.
AB - In this study, three nanos gene subtypes (Lcnanos1, Lcnanos2 and Lcnanos3) from
Larimichthys crocea, were cloned and characterized. We determined the spatio
temporal expression patterns of each subtype in tissues as well as the cellular
localization of mRNA in embryos. Results showed that deduced Nanos proteins have
two main homology domains: N-terminal CCR4/NOT1 deadenylase interaction domain
and highly conserved carboxy-terminal region bearing two conserved CCHC zinc
finger motifs. The expression levels of Lcnanos1 in testis were significantly
higher than other tissues, followed by heart, brain, eye, and ovary.
Nevertheless, both Lcnanos2 and Lcnanos3 were restrictedly expressed in testis
and ovary, respectively. No signals of Lcnanos1 and Lcnanos2 expression were
detected at any developmental stages during embryogenesis. On the contrary, the
signals of Lcnanos3 were detected in all stages examined. Lcnanos3 transcripts
were firstly localized to the distal end of cleavage furrow at the 2-cell stage.
Subsequently, mounting positive signals started to appear in a small number of
cells as the embryo developed to blastula stage and early-gastrula stage. As
development proceeded, positive signals were found in the primitive gonadal
ridge. These cells of Lcnanos3 positive signals implied the specification of the
future PGCs at this stage. It also suggested that PGCs of croaker originate from
four clusters of cells which inherit maternal germ plasm at blastula stage.
Furthermore, we preliminarily analyzed the migration route of PGCs in embryos of
L. crocea. In short, this study laid the foundation for studies on specification
and development of germ cell from L. crocea during embryogenesis.
PMID- 29331524
TI - Strategies and technical challenges for imaging oligometastatic disease:
Recommendations from the European Organisation for Research and Treatment of
Cancer imaging group.
AB - Patients with oligometastatic disease (OMD) often have controllable symptoms, and
cures are possible. Technical improvements in surgery and radiotherapy have
introduced the option of metastasis-directed ablative therapies as an adjunct or
alternative to standard-of-care systemic therapies. Several clinical trials and
registries are investigating the benefit of these therapeutic approaches across
several cancer sites. This requires that patients are correctly included and
followed with appropriate imaging. This article discusses the evidence and offers
recommendations for the implementation of standard-of-care (Response Evaluation
Criteria in Solid Tumours measurements on computed tomography [CT], magnetic
resonance imaging [MRI] and bone scintigraphy) and advanced imaging modalities
(functional, metabolic and radionuclide targeted) for identifying and following
up patients with OMD. Imaging requirements for recognising OMD vary with tumour
type, metastatic location, and timing of measurement in relation to previous
treatment. At each point in the disease cycle (diagnosis, response assessment and
follow-up), imaging must be tailored to the clinical question and the context of
prior treatment. The differential use of whole-body approaches such as 18F-FDG
positron emission tomography (PET)/CT, diffusion-weighted MRI, 18F-Choline-PET/CT
and 68Ga-prostate specific membrane antigen-PET/CT require rationalisation
depending on clinical risk assessment. Optimal standardised imaging approaches
will enable OMD trials to document patterns of disease progression and outcomes
of treatment. Quality assured and quality controlled imaging data included in
databases such as the European Organisation for Research and Treatment of Cancer
Imaging platform for the Oligocare trial (a prospective, large-scale
observational basket study being set up to collect outcome data from patients
with OMD treated with radiation therapy) will establish a large and high-quality
imaging warehouse for future research.
PMID- 29331525
TI - Production and characterization of ectoine using a moderately halophilic strain
Halomonas salina BCRC17875.
AB - This study attempted to utilize Halomonas salina BCRC17875 to produce ectoine by
optimizing the agitation speed and medium composition. In addition, the chemical
structure of ectoine produced by H. salina BCRC17875 was determined. The results
indicate that ectoine production reached 3.65 g/L at 38 h of cultivation when the
agitation rate and NaCl concentration were fixed at 200 rpm and 2.0 M,
respectively. It reached 9.20 g/L at 44 h of cultivation when the major medium
components were yeast extract (56 g/L), glutamate (74.40 g/L), and ammonium
sulfate (14 g/L). After the nitrogen concentration had been evaluated, evaluation
of the nitrogen concentration revealed that the ectoine production reached 11.80
g/L at 44 h of cultivation when 56 g/L of yeast extract and 28 g/L of ammonium
sulfate were used. Ectoine production reached 13.96 g/L at 44 h of cultivation
when the carbon/nitrogen ratio was fixed at 3/1 using 84 g/L of yeast extract and
28 g/L of ammonium sulfate. Furthermore, the identification of ectoine were
identified and characterized by fast atom bombardment mass spectrometry (FAB-MS)
and 1H NMR. The results demonstrated a fermentation strategy was successful in
increasing ectoine production, and that the fermentation medium of ectoine had
commercialization potential.
PMID- 29331527
TI - Construction of sake yeast with low production of dimethyl trisulfide precursor
by a self-cloning method.
AB - Dimethyl trisulfide (DMTS) is the primary component responsible for "hineka", the
stale aroma of Japanese sake. Deletion of the MRI1 or MDE1 gene of sake yeast,
encoding 5'-methylthioribose-1-phosphate isomerase and 5'-methylthioribulose-1
phosphate dehydratase, respectively, has been reported to greatly reduce the
amount of DMTS precursor (DMTS-P1) in sake and to suppress the formation of DMTS
during storage. In this study, we constructed sake yeast strains lacking MRI1
gene function by a self-cloning method. Two methods were applied: in one, a stop
codon was introduced in the MRI1 ORF by point mutation; in the other, the entire
MRI1 ORF was deleted from the genome. In both methods, a plasmid vector
containing drug-resistance and counter-selectable markers was used to introduce
the mutation. We successfully obtained the strains, which did not contain the
plasmid sequences, by both methods. Small-scale sake brewing tests using these SC
strains (strains obtained by the self-cloning method) found that DMTS-P1 was
hardly detected in sake brewed with SC strains, and DMTS production after sake
storage was greatly reduced as compared with the parent strain. The components of
brewed sake were almost the same between the SC and parent strains. These results
suggest that SC strains can produce sake with higher flavor stability without
changing the sake brewing properties.
PMID- 29331526
TI - Valerate production by Megasphaera elsdenii isolated from pig feces.
AB - Megasphaera elsdenii is able to produce several short-chain fatty acids (SCFAs),
such as acetate, propionate, butyrate, and valerate. These SCFAs serve as an
energy source for host animals and play an important role in gut health. In this
study, M. elsdenii was isolated from pig feces that had been collected from two
farms located in distinct areas of Japan. These M. elsdenii isolates were
genotyped, and 7 representative strains were selected. When these 7 strains and
M. elsdenii JCM 1772T were cultured with lactate for 24 h, all 7 strains produced
valerate as a predominant SCFA. Therefore, the valerate-producing M. elsdenii
inhabits a wide area of Japan. In contrast, M. elsdenii JCM 1772T produced
acetate, propionate, butyrate, and valerate at similar levels. When the Y2
strain, one of the 7 representative strains, was cultured without lactate, low
levels of valerate accumulated. In contrast, in a time course of lactate
fermentation by the Y2 strain, lactate was rapidly consumed, and acetate and
propionate were produced after 6 h of incubation. Thereafter, acetate and
propionate were consumed from 6 to 12 h after the start of the incubation, and
valerate and butyrate were produced. In most of the previously described M.
elsdenii strains, valerate was not a predominant SCFA. Therefore, the M. elsdenii
Y2 strain showed an unique metabolism in which valerate was produced as a primary
end product of lactate fermentation.
PMID- 29331528
TI - Expression of a thermotolerant laccase from Pycnoporus sanguineus in Trichoderma
reesei and its application in the degradation of bisphenol A.
AB - The laccase gene from Pycnoporus sanguineus was cloned and inserted between the
strong Pcbh1 promoter and the Tcbh1 terminator from Trichoderma reesei to form
the recombinant plasmid pCH-lac. Using Agrobacterium-mediated technique, the pCH
lac was integrated into the chromosomes of T. reesei. Twenty positive
transformants were obtained by employing hygromycin B as a selective agent. PCR
was used to confirm that the laccase gene was integrated into the chromosomal DNA
of T. reesei. Laccase production by recombinant transformants was performed in
shaking flasks, and the activity of laccase reached 8.8 IU/mL after 96-h
fermentation under a batch process, and 17.7 IU/mL after 144-h fermentation using
a fed-batch process. SDS-PAGE analysis of the fermentation broth showed that the
molecular mass of the protein was about 68 kDa, almost the same as that of the
laccase produced by P. sanguineus, which indicated that laccase was successfully
expressed in T. reesei and secreted out of the cells. The laccase produced by the
recombinant T. reesei showed good thermal stability, and could degrade the toxic
phenolic material bisphenol A efficiently, after 1-h reaction with 0.06 IU/mL
laccase and 0.5 mmol/L ABTS as the mediator at 60 degrees C and pH 4.5, the
degradation rate reached 95%, which demonstrated that it had great potential
value in treating the household garbage and wastewater containing the bisphenol
A.
PMID- 29331529
TI - Effect of acids produced from carbohydrate metabolism in cryoprotectants on the
viability of freeze-dried Lactobacillus and prediction of optimal initial cell
concentration.
AB - For the industrial production of probiotics powder, various sugars have been used
as cryoprotectants to preserve probiotics during freeze-drying. Some of these
sugars can be metabolized by Lactobacillus with the production of acids during
the mix. In this study, we investigated the effect of acids on ATPase, beta
galactosidase, lactate dehydrogenase (LDH), integrity and fluidity of cell
membrane and the survival rate of Lactobacillus during freeze-drying. In the
presence of Lactobacillus, acids were produced from cryoprotectants containing
fermentable sugars before freezing, resulting in a decrease in the pH of the
bacterial suspension to below 5.0. During freeze-drying, the acids caused a loss
of viability of Lactobacillus due to aggravated damage to ATPase, beta
galactosidase and cell membrane fluidity, but not LDH and cell membrane
integrity. This finding implied that cryoprotectants that do not lead to the
production of acids are effective in improving the survival rate of freeze-dried
Lactobacillus. Here, a new formula was proposed for a protectant containing whey
protein isolate (WPI) and rhamnose, which were not metabolized. In addition,
linear-regression analyses were performed on the proportion of cryoprotectants
(M) against cell paste (m), total cell count (N), total surface area (St) and
total volume (Vt) of bacteria for 100% survival rate. The total surface areas of
bacteria were found to be highly correlated with the amount of proposed
cryoprotectant. The following prediction equation was established for the optimal
initial cell concentration for a 100% survival rate of freeze-dried
Lactobacillus: N (4pir2+2pil)=(0.66+/-0.03)M.
PMID- 29331530
TI - A qualitative synthesis of pharmacist, other health professional and lay
perspectives on the role of community pharmacy in facilitating care for people
with long-term conditions.
AB - BACKGROUND: There is increasing interest in an enhanced role for community
pharmacy (CP) in facilitating care for people with long-term conditions (LTCs).
It is important to understand the perspectives of stakeholders in order to
identify key issues that may impact on future development of the role and related
services. OBJECTIVES: Explore pharmacist, other health professional and lay
perspectives on the role of CP in facilitating care for people with LTCs.
METHODS: Synthesis of qualitative research from UK based studies published
between 2007 and January 2017 using a meta-ethnographic interpretative approach.
RESULTS: Variation in the conceptualisation of the role of CP in facilitating the
care of people with LTCs was apparent across and within lay and health
professional accounts. Despite evidence of positive attitudes and a culture
amenable to change, there remains a lack of clarity about the existing and
potential role of the pharmacist in this area. A theoretical framework is
proposed that highlights the dynamic nature of the process involved in the
development of lay and health professionals' understanding of the role and
engagement with services. Influences on this process include experience and
perceived need, service operationalisation, and ongoing developments within wider
healthcare policy and commercial environments. Perceived integration with
existing professional and peer support structures, views about traditional
medical hierarchies and concerns about potential duplication are important
influences on the value attributed to the role of CP and the services provided.
CONCLUSIONS: There is acknowledged potential for an extended role in CP to
support the care of people with LTCs. To ensure the likelihood of successful
engagement with patients and positive health outcomes, developments should
acknowledge influences within and beyond the CP setting. Potential overlap with
other healthcare services should be explicitly addressed, ensuring this is framed
and delivered as valued reinforcement with clearly defined boundaries of
responsibility.
PMID- 29331531
TI - Profiles of beta-Amyloid Peptides and Key Secretases in Brain Autopsy Samples
Differ with Sex and APOE epsilon4 Status: Impact for Risk and Progression of
Alzheimer Disease.
AB - The APOE epsilon4 allele was originally reported to contribute to risk of
Alzheimer's disease (AD) in women, yet male and female AD patient-derived data
are routinely pooled. Histopathological hallmarks of AD include neurofibrillary
tangles centered on hyperphosphorylated Tau and plaques composed of the beta
amyloid (Abeta) peptide that is derived by sequential secretase-mediated cleavage
of the Amyloid Protein Precursor (APP). We chose to examine profiles of Abeta(1
40), Abeta(1-42), and N-truncated (i.e., p3-related) fragments in the plaque
associated fraction of autopsied cortical and corresponding hippocampal samples
from donors with a diagnosis of early-onset (EOAD) and late-onset (LOAD) AD.
Levels of Abeta(1-40), Abeta(1-42), and the p3 fragment-enriched pool were
increased in EOAD and LOAD samples, and correlated well within -but not between-
regions. Counterintuitively, these increases were similar regardless of the AD
donor's APOE epsilon4 status. Focusing on the donor's sex and APOE epsilon4
status as nominal variables (i.e., omitting diagnosis from the stratification)
revealed that increases in Abeta peptides were specific to female carriers of the
epsilon4 allele and correlated with the proportional expression of BACE1/beta
secretase and ADAM10/alpha-secretase in the cortex and with nicastrin (gamma
secretase) expression in the hippocampus. These data preliminarily support the
possibility that AD follows distinct amyloidogenic processes in males and
females, and that the APOE epsilon4 allele exerts a major influence on the
disease process, particularly in women. This knowledge could significantly impact
the (re)interpretation of unsuccessful outcomes of clinical interventions
targeting either Abeta peptides directly or the secretases implicated in APP
processing.
PMID- 29331532
TI - High-fat Diet Mediates Anxiolytic-like Behaviors in a Time-dependent Manner
Through the Regulation of SIRT1 in the Brain.
AB - The consumption of a high-fat diet (HFD) and obesity have been associated not
only with metabolic diseases but also with neuropsychiatric diseases, such as
depression and anxiety. However, results on the effects of an HFD on anxiety are
controversial, since both anxiogenic and anxiolytic effects have been reported.
In this study, we evaluated the effects of both short- and long-term intake of an
HFD on anxiety-like behaviors. To explore the impact of time on the association
between an HFD and anxiety, mice were fed with an HFD for 4 weeks or 12 weeks.
Compared with control-diet mice, mice given an HFD for 4 weeks displayed
anxiolytic-like behaviors. At the same time, we observed decreased SIRT1
expression in the mPFC and the amygdala of HFD-fed mice. Moreover, resveratrol,
an activator of SIRT1, reversed the anxiolytic-like behaviors in HFD-fed mice.
However, after 12 weeks of consuming a high-fat diet, mice did not exhibit any
anti-anxiety behavior or further decreases in SIRT1 expression in the
aforementioned brain regions compared with CD-fed mice. When EX-527, a SIRT1
inhibitor, was intraperitoneally injected, we observed anxiolytic effects in the
CD-fed mice but not in the 12-week HFD-fed mice. Collectively, our data
demonstrate that exposure to a short-term HFD can induce anxiolytic behaviors,
which may be associated with decreased SIRT1 in the mPFC and the amygdala.
However, this effect is abolished when the high-fat diet is extended to 12 weeks.
Together, these results demonstrate that SIRT1 plays an essential role in
regulating mood-related behaviors in HFD-fed mice.
PMID- 29331533
TI - A woman's hand and a lion's heart: Skills and attributes for rural midwifery
practice in New Zealand and Scotland.
AB - OBJECTIVE: the complex and challenging nature of rural midwifery is a global
issue. New Zealand and Scotland both face similar ongoing challenges in
sustaining a rural midwifery workforce, and understanding the best preparation
for rural midwifery practice. This study aimed to explore the range of skills,
qualities and professional expertise needed for remote and rural midwifery
practice. DESIGN: online mixed methods: An initial questionnaire via a
confidential SurveyMonkey(r) was circulated to all midwives working with rural
women and families in New Zealand and Scotland. A follow-up online discussion
forum offered midwives a secure environment to share their views about the
specific skills, qualities and challenges and how rural midwifery can be
sustained. Data presented were analysed using qualitative descriptive thematic
analysis. SETTING AND PARTICIPANTS: 222 midwives participated in this online
study with 145 from New Zealand and 77 from Scotland. FINDINGS: underpinning
rural midwifery practice is the essence of 'fortitude' which includes having the
determination, resilience, and resourcefulness to deal with the many challenges
faced in everyday practice and to safeguard midwifery care for women within their
rural communities. KEY CONCLUSIONS: rural midwives in New Zealand and Scotland
who work in rural practice specifically enhance skills such as preparedness,
resourcefulness and developing meaningful relationships with women and other
colleagues which enables them to safeguard rural birth. IMPLICATIONS FOR
PRACTICE: findings will inform the preparation of midwives for rural midwifery
practice.
PMID- 29331534
TI - Perinatal palliative care: Integration in a United States nurse midwifery
education program.
AB - Midwifery students with perinatal palliative care education develop a skillset to
provide holistic midwifery care to women and families who are experiencing
stillbirth or life-limiting fetal diagnoses. This paper presents a model of
perinatal palliative care in a United States midwifery education program. By
utilizing evidence based practices and national programs, perinatal palliative
care can be threaded through midwifery curricula to achieve international
standards of practice and competencies. Most importantly, enhancing perinatal
palliative care education will better prepare future midwives for when a birth
outcome is not what was expected at the outset of a pregnancy.
PMID- 29331535
TI - Estrogen deprivation aggravates cardiometabolic dysfunction in obese-insulin
resistant rats through the impairment of cardiac mitochondrial dynamics.
AB - The incidence of cardiovascular disease and metabolic syndrome increases after
the onset of menopause, suggesting estrogen has a vital role in their prevention.
Mitochondrial dynamics are known to play an important role in the maintenance of
cardiac physiological function. However, the effects of estrogen deprivation on
cardiometabolic status and cardiac mitochondrial dynamics under conditions of
obese-insulin resistance have never been investigated. We hypothesized that
estrogen deprivation aggravates cardiac dysfunction through increased cardiac
mitochondrial fission in obese-insulin resistant rats. Female rats were fed on
either a high fat (HFD, 57.60% fat) or normal (ND, 19.77% fat) diet for 13 weeks.
The rats were then divided into 4 groups. Two sham groups (HFS and NDS) and 2
operated or ovariectomized (HFO and NDO) groups (n = 8/group). Six weeks after
surgery, metabolic status, heart rate variability (HRV), left ventricular (LV)
function, cardiac mitochondrial function and dynamics, and metabolic parameters
were determined. Insulin resistance developed in NDO, HFS and HFO rats as
indicated by increased plasma insulin and HOMA index. Although rats in both NDO
and HFS groups had markedly impaired LV function indicated by reduced %LVFS and
impaired cardiac mitochondrial function, rats in the HFO group had the most
severe impairments. Moreover, the estrogen deprived rats (NDO and HFO) had
increased cardiac mitochondrial fission through activation of phosphorylation of
Drp-1 at serine 616. Our findings indicated that estrogen deprivation caused the
worsening of LV dysfunction through increased cardiac mitochondrial fission in
obese-insulin resistant rats.
PMID- 29331536
TI - Chronic inflammation and sarcopenia: A regenerative cell therapy perspective.
AB - Sarcopenia is characterized by reduced skeletal muscle mass and strength in older
individuals. It is one of the leading cause of physical limitation in older
adults, and associated with wide spectrum of adverse events including disability
and mortality. The phenomenon of chronic-inflammation or inflamm-aging with aging
is known to be a major contributor to myriad of geriatric conditions including
sarcopenia. Recent advances in regenerative medicine, in particular cell therapy
have opened up new possibilities to ameliorate broad range of inflammatory
disorders. In this context, we will discuss on possibilities of modulation of the
chronic-inflammatory activation in older adults using regenerative cell therapy
strategies. This review is an effort toward reducing the growing burden of
sarcopenia related disability and dependency in the aging population.
PMID- 29331537
TI - Preparation of acetylated nanofibrillated cellulose from corn stalk
microcrystalline cellulose and its reinforcing effect on starch films.
AB - Acetylated nanofibrillated cellulose (ANFC) with different degrees of
substitution (DS) was prepared from corn-stalk microcrystalline cellulose (MCC)
using chemical-mechanical combined processes. The physicochemical properties of
nanofibrillated cellulose (NFC) and ANFC were investigated together with the
influence of added nanoparticles on the mechanical properties of starch films.
The acetylation reaction was monitored by Fourier transform infrared (FT-IR) and
titration. Particle size and morphological of NFC and ANFC were studied by atomic
force microscope (AFM). The results suggested that NFC had nano-order-unit web
like network with mean diameter of ~24 nm. The thermostability of all samples was
found to decrease as the modification extent rose, and mechanical disposal
revealed no significant influence on the DS and crystalline structure of
cellulose. The ANFC with the DS value of 0.35 demonstrated the best enhancement
effect on starch films, with increased tension strength (TS) by 201%. The tensile
tests confirmed that the web-like network structure of NFC was more conducive to
strength, and proper chemical modification could improve the uniform dispersion
of nano-fillers in starch to result in higher strength performances.
PMID- 29331538
TI - Differential lipid metabolism outcomes associated with ADRB2 gene polymorphisms
in response to two dietary interventions in overweight/obese subjects.
AB - BACKGROUND AND AIMS: A precise nutrigenetic management of hypercholesterolemia
involves the understanding of the interactions between the individual's genotype
and dietary intake. The aim of this study was to analyze the response to two
dietary energy-restricted interventions on cholesterol changes in carriers of two
ADRB2 polymorphisms. METHODS AND RESULTS: A 4-month nutritional intervention was
conducted involving two different hypo-energetic diets based on low-fat (LF) and
moderately high-protein (MHP) dietary patterns. A total of 107 unrelated
overweight/obese individuals were genotyped for two ADRB2 non-synonymous
polymorphisms: Arg16Gly (rs1042713) and Gln27Glu (rs1042714). Genotyping was
performed by next-generation sequencing and haplotypes were phenotypically
screened. Anthropometric measurements and the biochemical profile were assessed
by conventional methods. Both diets induced cholesterol decreases at the end of
both nutritional interventions. Interestingly, phenotypical differences were
observed according to the Arg16Gly polymorphism. Within the MHP group, Gly16Gly
homozygotes had lower reductions in total cholesterol (-6.5 mg/dL vs. -24.2
mg/dL, p = 0.009), LDL-c levels (-1.4 mg/dL vs. -16.5 mg/dL, p = 0.005), and non
HDL-c (-4.5 mg/dL vs. -21.5 mg/dL, p = 0.008) than Arg16 allele carriers.
Conversely, within the LF group, Gly16Gly homozygotes underwent similar falls in
total cholesterol (-18.5 mg/dL vs. -18.7 mg/dL, ns), LDL-c levels (-9.7 mg/dL vs.
-13.1 mg/dL, ns), and non-HDL-c (-15.3 mg/dL vs. -15.7 mg/dL, ns) than Arg16
allele carriers. The Gln27Glu polymorphism and the Gly16/Glu27 haplotype showed
similar, but not greater effects. CONCLUSIONS: An energy-restricted LF diet could
be more beneficial than a MHP diet to reduce serum cholesterol, LDL-c, and non
HDL-c among Gly16Gly genotype carriers. CLINICALTRIALS.GOV: Identifier:
NCT02737267.
PMID- 29331540
TI - Plant Flowering: Imposing DNA Specificity on Histone-Fold Subunits.
AB - CONSTANS (CO) is a master regulator of flowering time, although the mechanisms
underlying its role as a transcriptional regulator are not well understood. The
DNA-binding domain of CO shares homology with that of NUCLEAR FACTOR YA (NF-YA),
a subunit of the CCAAT-binding trimer NF-Y. Recent publications indicate that CO
and its rice homolog HEADING DATE 1 (Hd1) form heterotrimers with the histone
fold subunits of NF-Y to efficiently bind promoter elements in the florigen
genes. Differences in the DNA-binding specificities of NF-Y and NF-CO can be
conceptualized based on our knowledge of the 3D structure of the NF-Y/CCAAT
complex. Here we discuss the modes of assembly of NF-Y-like heterotrimers and
possible models for their activity as flexible sequence-specific transcriptional
regulators.
PMID- 29331541
TI - Perilesional edema in brain cancer: Independent prognosticator or epiphenomenon
of biomolecular signature?
PMID- 29331542
TI - Concurrent chemoradiotherapy alone is feasible for esophageal squamous cell
carcinoma patients not suitable for surgery.
PMID- 29331539
TI - Serum vitamin D deficiency and risk of hospitalization for heart failure:
Prospective results from the Moli-sani study.
AB - BACKGROUND AND AIMS: Evidence indicates that Vitamin D deficiency may be
associated with increased risk of cardiovascular disease, although findings on
risk of heart failure (HF) are controversial. We investigated the relationship
between serum Vitamin D and the incidence of hospitalization for HF in a large
prospective cohort of Italian adults. METHODS AND RESULTS: 19,092 (49% men, age
range 35-99 years) HF-free individuals from the Moli-sani study, with complete
data on serum Vitamin D (25-hydroxyvitamin) levels and incident hospitalized HF,
were analysed. The cohort was followed up for a median of 6.2 years. Baseline
serum Vitamin D levels were categorized in deficient (<10 ng/mL), insufficient
(10-29 ng/mL), and normal (>=30 ng/mL) Incident cases of hospitalization for HF
were identified by linkage with the regional hospital discharge registry. Hazard
ratios (HRs) were calculated using Cox-proportional hazard models. The prevalence
of normal, insufficient or deficient levels of Vitamin D was 12.2%, 79.6% and
8.2%, respectively. During follow-up, 562 admissions to hospital for HF were
identified. The incidence of HF was 1.6%, 2.9% and 5.3%, respectively in subjects
with normal, insufficient and deficient levels of Vitamin D. After multivariable
analysis, individuals with deficiency of Vitamin D had a higher risk of
hospitalization for HF (HR: 1.61, 95%CI: 1.06-2.43) than those with normal
levels. Further adjustment for subclinical inflammation did not substantially
change the association between Vitamin D deficiency and HF. CONCLUSION:
Deficiency of Vitamin D was associated, independently of known HF risk factors,
with an increased risk of hospitalization for HF in an Italian adult population.
PMID- 29331543
TI - Consolidation chemotherapy after definite concurrent chemoradiation in patients
with non-operable esophageal cancer: Is it useful?
PMID- 29331544
TI - Role of bronchoscopy in foreign body aspiration management in adults: A seven
year retrospective study.
PMID- 29331545
TI - Reply by Authors.
PMID- 29331546
TI - Clinically Localized Prostate Cancer: AUA/ASTRO/SUO Guideline. Part II:
Recommended Approaches and Details of Specific Care Options.
AB - PURPOSE: This guideline is structured to provide a clinical framework stratified
by cancer severity to facilitate care decisions and guide the specifics of
implementing the selected management options. The summary presented herein
represents Part II of the two-part series dedicated to Clinically Localized
Prostate Cancer: AUA/ASTRO/SUO Guideline discussing risk stratification and care
options by cancer severity. Please refer to Part I for discussion of specific
care options and outcome expectations and management. MATERIALS AND METHODS: The
systematic review utilized in the creation of this guideline was completed by the
Agency for Healthcare Research and Quality and through additional supplementation
by ECRI Institute. This review included articles published between January 2007
and March 2014 with an update search conducted through August 2016. When
sufficient evidence existed, the body of evidence for a particular treatment was
assigned a strength rating of A (high), B (moderate), or C (low) for support of
Strong, Moderate, or Conditional Recommendations. Additional information is
provided as Clinical Principles and Expert Opinions (table 2 in supplementary
unabridged guideline, http://jurology.com/). RESULTS: The AUA (American
Urological Association), ASTRO, and SUO (Society of Urologic Oncology) formulated
an evidence-based guideline based on a risk stratified clinical framework for the
management of localized prostate cancer. CONCLUSIONS: This guideline attempts to
improve a clinician's ability to treat patients diagnosed with localized prostate
cancer, but higher quality evidence in future trials will be essential to improve
the level of care for these patients. In all cases, patient preferences should be
considered when choosing a management strategy.
PMID- 29331547
TI - Editorial Comment.
PMID- 29331549
TI - Is sequence awareness mandatory for perceptual sequence learning: An assessment
using a pure perceptual sequence learning design.
AB - We examined the role of sequence awareness in a pure perceptual sequence learning
design. Participants had to react to the target's colour that changed according
to a perceptual sequence. By varying the mapping of the target's colour onto the
response keys, motor responses changed randomly. The effect of sequence awareness
on perceptual sequence learning was determined by manipulating the learning
instructions (explicit versus implicit) and assessing the amount of sequence
awareness after the experiment. In the explicit instruction condition (n = 15),
participants were instructed to intentionally search for the colour sequence,
whereas in the implicit instruction condition (n = 15), they were left uninformed
about the sequenced nature of the task. Sequence awareness after the sequence
learning task was tested by means of a questionnaire and the process-dissociation
procedure. The results showed that the instruction manipulation had no effect on
the amount of perceptual sequence learning. Based on their report to have
actively applied their sequence knowledge during the experiment, participants
were subsequently regrouped in a sequence strategy group (n = 14, of which 4
participants from the implicit instruction condition and 10 participants from the
explicit instruction condition) and a no-sequence strategy group (n = 16, of
which 11 participants from the implicit instruction condition and 5 participants
from the explicit instruction condition). Only participants of the sequence
strategy group showed reliable perceptual sequence learning and sequence
awareness. These results indicate that perceptual sequence learning depends upon
the continuous employment of strategic cognitive control processes on sequence
knowledge. Sequence awareness is suggested to be a necessary but not sufficient
condition for perceptual learning to take place.
PMID- 29331548
TI - Effect of outpatient antibiotics for urinary tract infections on antimicrobial
resistance among commensal Enterobacteriaceae: a multinational prospective cohort
study.
AB - OBJECTIVES: We quantified the impact of antibiotics prescribed in primary care
for urinary tract infections (UTIs) on intestinal colonization by ciprofloxacin
resistant (CIP-RE) and extended-spectrum beta-lactamase-producing
Enterobacteriaceae (ESBL-PE), while accounting for household clustering. METHODS:
Prospective cohort study from January 2011 to August 2013 at primary care sites
in Belgium, Poland and Switzerland. We recruited outpatients requiring
antibiotics for suspected UTIs or asymptomatic bacteriuria (exposed patients),
outpatients not requiring antibiotics (non-exposed patients), and one to three
household contacts for each patient. Faecal samples were tested for CIP-RE, ESBL
PE, nitrofurantoin-resistant Enterobacteriaceae (NIT-RE) and any
Enterobacteriaceae at baseline (S1), end of antibiotics (S2) and 28 days after S2
(S3). RESULTS: We included 300 households (205 exposed, 95 non-exposed) with 716
participants. Most exposed patients received nitrofurans (86; 42%) or
fluoroquinolones (76; 37%). CIP-RE were identified in 16% (328/2033) of samples
from 202 (28%) participants. Fluoroquinolone treatment caused transient
suppression of Enterobacteriaceae (S2) and subsequent two-fold increase in CIP-RE
prevalence at S3 (adjusted prevalence ratio (aPR) 2.0, 95% CI 1.2-3.4), with
corresponding number-needed-to-harm of 12. Nitrofurans had no impact on CIP-RE
(aPR 1.0, 95% CI 0.5-1.8) or NIT-RE. ESBL-PE were identified in 5% (107/2058) of
samples from 71 (10%) participants, with colonization not associated with
antibiotic exposure. Household exposure to CIP-RE or ESBL-PE was associated with
increased individual risk of colonization: aPR 1.8 (95% CI 1.3-2.5) and 3.4 (95%
CI 1.3-9.0), respectively. CONCLUSIONS: These findings support avoidance of
fluoroquinolones for first-line UTI therapy in primary care, and suggest
potential for interventions that interrupt household circulation of resistant
Enterobacteriaceae.
PMID- 29331551
TI - Difficult Removal of a Kinked Swan-Ganz Catheter.
PMID- 29331550
TI - Double-Lumen Endotracheal Tube Placement: Knowing Depth of Insertion Firsthand
May Make a Difference.
PMID- 29331552
TI - Malperfusion During Hypothermic Antegrade Cerebral Perfusion: Cerebral Perfusion
Index-An Early Indicator Compared to Cerebral Oximetry.
PMID- 29331553
TI - Unexpected Findings in a Man with a Repaired Type A Aortic Dissection and a New
Stroke.
PMID- 29331554
TI - Potential Role of Transfontanelle Ultrasound for Infants Undergoing Modified
Blalock-Taussig Shunt.
AB - OBJECTIVE: Transfontanelle ultrasound is a noninvasive method for assessing
cerebral blood flow in neonates and infants. The authors applied this technique
as a point-of-care tool, before and after modified Blalock-Taussig shunt
procedure, to evaluate cerebral perfusion. DESIGN: Retrospective, observational
study. SETTING: Tertiary care children's hospital. PARTICIPANTS: Ten infants
undergoing modified Blalock-Taussig shunt procedure. OBSERVATION: Transfontanelle
ultrasound examinations with modified resistive index were analyzed before and
after the modified Blalock-Taussig shunt procedure. MEASUREMENTS AND MAIN
RESULTS: Two infants died and 2 patients required a revision procedure due to
shunt thrombosis. Baseline-modified resistive index and regional cerebral
oxygenation were comparable between the right and left hemisphere. However, after
the procedure, the modified resistive index decreased at both sides of the
internal carotid arteries compared with baseline values (p value right side =
0.012, left side = 0.036) and was greater at the ipsilateral internal carotid
arteries with the shunt (p = 0.012, mean difference = 0.07, 95% confidence
interval [CI] 0.02-0.12). Four infants with the large patent ductus arteriosus
presented diastolic reverse flows at both internal carotid arteries at baseline.
However, the diastolic reverse flow disappeared after the procedure. An infant
who developed diastolic reverse flow after the procedure, died. CONCLUSIONS:
Transfontanelle ultrasound is a feasible tool for assessing the pattern of shunt
flow and cerebral perfusion before and after the modified Blalock-Taussig shunt
procedure. The transfontanelle ultrasound examinations may have potential role in
assessing "over-shunting," but it needs more studies.
PMID- 29331555
TI - Preoperative Thromboelastographic Profile of Patients with Congenital Heart
Disease: Association of Hypercoagulability and Decreased Heparin Response.
AB - OBJECTIVE: To describe the demographic and thromboelastographic characteristics
of patients with congenital heart disease presenting with decreased heparin
response before cardiac surgery. DESIGN: Retrospective, observational study.
SETTING: Single institution, tertiary, academic, university hospital.
PARTICIPANTS: The study comprised 496 pediatric and adult patients undergoing
cardiac surgery for congenital heart disease. INTERVENTIONS: Retrospective review
of medical records. MEASUREMENTS AND MAIN RESULTS: Data on preoperative
thromboelastography (TEG), demographics, and response to heparin were collected
retrospectively. Logistic regression analysis was used to study the association
between TEG and response to heparin. Decreased heparin response (defined as
activated clotting time <480 s initial bolus of 300 U/kg heparin) was observed in
23.6% of patients presenting for surgery. Age distribution and preoperative
coagulation profiles were similar for both nonresponders and responders to
heparin. Preoperatively, nonresponders demonstrated all thromboelastrographic
characteristics consistent with a hypercoagulable profile (shorter reaction time,
K value, wider angle, and maximum amplitude). Univariate logistic regression
identified all TEG variables significantly associated with decreased heparin
response. After adjustment for age, procedure type, and the presence of cyanosis,
a multivariate logistic regression model identified the TEG variable K (<=1.3
min) as being significantly associated with decreased heparin response (odds
ratio 3.7; confidence interval 2.3-5.8; p < 0.0001). CONCLUSIONS: Decreased
response to heparin before cardiac surgery in patients with congenital heart
disease is associated with preoperative hypercoagulability identified using a
viscoelastic test. Additional studies are needed to better understand the
etiology of decreased heparin response and potential clinical strategies to
improve anticoagulation management.
PMID- 29331556
TI - Polypoidal Choroidal Vasculopathy: Definition, Pathogenesis, Diagnosis, and
Management.
AB - Polypoidal choroidal vasculopathy (PCV) is an age-related macular degeneration
(AMD) subtype and is seen particularly in Asians. Previous studies have suggested
disparity in response to intravitreal injections of anti-vascular endothelial
growth factor (VEGF) agents between PCV and typical AMD, and thus, the preferred
treatment for PCV has remained unclear. Recent research has provided novel
insights into the pathogenesis of PCV, and imaging studies based on OCT suggest
that PCV belongs to a spectrum of conditions characterized by pachychoroid, in
which disturbance in the choroidal circulation seems to be central to its
pathogenesis. Advances in imaging, including enhanced depth imaging, swept-source
OCT, en face OCT, and OCT angiography, have facilitated the diagnosis of PCV.
Importantly, 2 large, multicenter randomized clinical trials evaluating the
safety and efficacy of anti-VEGF monotherapy and combination with photodynamic
therapy (PDT) recently reported initial first-year outcomes, providing level I
evidence to guide clinicians in choosing the most appropriate therapy for PCV. In
this review, we summarize the latest updates in the epidemiologic features,
pathogenesis, and advances in imaging and treatment trials, with a focus on the
most recent key clinical trials. Finally, we propose current management
guidelines and recommendations to help clinicians manage patients with PCV.
Remaining gaps in current understanding of PCV, such as significance of polyp
closure, high recurrence rate, and heterogeneity within PCV, are highlighted
where further research is needed.
PMID- 29331557
TI - Soil-to-plant transfer factors of natural radionuclides (226Ra and 40K) in
selected Thai medicinal plants.
AB - A soil-to-plant transfer factor (TF) is an important parameter that could be used
to estimate radionuclides levels in medicinal plants. This work reports
concentrations of natural radionuclides (226Ra and 40K) and TFs in six Thai
medicinal plants grown in central Thailand using an HPGe gamma ray spectrometer.
Either root, leaf, or flower parts of each medicinal plant were selected for use
in the investigation according to their practical uses in traditional medicine.
The results showed that due to K being essential in plants, 40K had higher
arithmetic means of activity concentrations and geometric means of TFs (geometric
standard deviations in parentheses) of 610 +/- 260 Bq kg-1 dry weight (DW) and
2.0 (1.4), respectively, than 226Ra, which had the activity concentrations and
TFs of 4.8 +/- 2.6 Bq kg-1 DW and 0.17 (1.8), respectively. The results also
showed that the leaves of medicinal plants had higher activity concentrations and
TFs than root and flower parts, probably due to higher metabolic activities in
leaves. Furthermore, there was good agreement between the results from the
current work and other similar reports on medicinal plants. The information
obtained from this work could strengthen knowledge of natural radionuclides in
plants and particularly increase available TF data on Thai medicinal plants.
PMID- 29331558
TI - High-resolution 129I bomb peak profile in an ice core from SE-Dome site,
Greenland.
AB - 129I in natural archives, such as ice cores, can be used as a proxy for human
nuclear activities, age marker, and environmental tracer. Currently, there is
only one published record of 129I in ice core (i.e., from Fiescherhorn Glacier,
Swiss Alps) and its limited time resolution (1-2 years) prevents the full use of
129I for the mentioned applications. Here we show 129I concentrations in an ice
core from SE-Dome, Greenland, covering years 1956-1976 at a time resolution of ~6
months, the most detailed record to date. Results revealed 129I bomb peaks in
years 1959, 1962, and 1963, associated to tests performed by the former Soviet
Union, one year prior, in its Novaya Zemlya test site. All 129I bomb peaks were
observed in winter (1958.9, 1962.1, and 1963.0), while tritium bomb peaks,
another prominent radionuclide associated with nuclear bomb testing, were
observed in spring or summer (1959.3, and 1963.6; Iizuka et al., 2017). These
results indicate that 129I bomb peaks can be used as annual and seasonal age
markers for these years. Furthermore, we found that 129I recorded nuclear fuel
reprocessing signals and that these can be potentially used to correct timing of
estimated 129I releases during years 1964-1976. Comparisons with other published
records of 129I in natural archives showed that 129I can be used as common age
marker and tracer for different types of records. Most notably, the 1963 129I
bomb peak can be used as common age marker for ice and coral cores, providing the
means to reconcile age models and associated trends from the polar and tropical
regions, respectively.
PMID- 29331559
TI - Experience of on-site disposal of production uranium-graphite nuclear reactor.
AB - The paper reported the experience gained in the course of decommissioning EI-2
Production Uranium-Graphite Nuclear Reactor. EI-2 was a production Uranium
Graphite Nuclear Reactor located on the Production and Demonstration Center for
Uranium-Graphite Reactors JSC (PDC UGR JSC) site of Seversk City, Tomsk Region,
Russia. EI-2 commenced its operation in 1958, and was shut down on December 28,
1990, having operated for the period of 33 years all together. The extra pure
grade graphite for the moderator, water for the coolant, and uranium metal for
the fuel were used in the reactor. During the operation nitrogen gas was passed
through the graphite stack of the reactor. In the process of decommissioning the
PDC UGR JSC site the cavities in the reactor space were filled with clay-based
materials. A specific composite barrier material based on clays and minerals of
Siberian Region was developed for the purpose. Numerical modeling demonstrated
the developed clay composite would make efficient geological barriers preventing
release of radionuclides into the environment.
PMID- 29331560
TI - The effects of sediment transport on temporal variation in radiocesium
concentrations in very shallow water off the southern coast of Fukushima, Japan.
AB - We studied the very shallow coastal water off Iwaki City, Fukushima Prefecture,
and investigated: (1) temporal variation in 137Cs concentrations; (2) particle
size distribution of sediments; and (3) the effect on variation by waves,
component-fractionated concentration of radiocesium and mineral composition at
three sampling stations (Yotsukura, Ena rocky reef and Ena sandy station). There
was a decline in 137Cs concentrations in sediment samples at all sampling
stations between 425 and 1173 days after the accident. All stations had
fluctuations in 137Cs concentrations between 425 and 800 days. At Ena sandy
station and Ena rocky reef stations the declines in 137Cs concentrations slowed
from about 800 days after the accident. Fluctuations in particle median diameters
were seen, as well as in 137Cs concentrations. At Yotsukura, where the
fluctuation in median diameter was small, a constant decrease in 137Cs
concentrations was observed. We considered that bioturbation may contribute the
constant decrease. At Ena sandy station, where the fluctuation of the median
diameter was large, the fluctuation in 137Cs concentrations was also large. The
movement of sediments was evaluated by the Shields parameter, and results
indicated that at any station where the sediment was moved more frequently, the
fluctuation in 137Cs concentrations was also large. The highly contaminated small
particles moved from our stations due to wave action between 425 and 800 days
after the accident. The remaining relatively large particles might contribute to
the slowing down in reduction of 137Cs concentrations from 800 days after the
accident. However, the 137Cs concentrations in sediments in very shallow water
off the southern coast of Fukushima may continue to decline over time.
PMID- 29331561
TI - Long-term outcome of neurological Wilson's disease.
AB - INTRODUCTION: Aim of the study was to characterize the clinical spectrum of long
term treated patients with Wilson's disease (WD) and to identify risk factors
influencing long-term outcome. METHODS: In a cross-sectional study 30 WD-patients
being treated for at least 2.5 and up to 31 years underwent a detailed clinical
investigation, scoring of clinical findings yielding 7 motor and 3 non-motor
subscores as well as laboratory testing. A factor analysis of these subscores and
laboratory parameters was performed to detect those items with the highest
influence on outcome, an ANOVA and subgroup analysis tested the influence of age,
age at onset of diagnosis and duration of treatment on outcome. A correlation
analysis was performed between clinical subscores and laboratory findings.
RESULTS: Three factors (F1-F3) characterized the clinical outcome (F1: tremor and
pathological reflexes; F2: dystonia and dysarthria; F3: cerebellar abnormalities
and gait), and three factors the laboratory findings (LF1: serum level of
ceruloplasmin; LF2: liver enzymes; LF3: INR). Mildly affected patients had an
elevated 24 h urinary copper excretion, more affected patients presented with
elevated liver enzymes. Six of the 7 motor subscores did not change with duration
of treatment, whereas tremor (p < .04), the total score (p < .02) and especially
the non-motor items (p < .001) significantly increased with duration of
treatment. The outcome of patients with neuropsychiatric abnormalities was
significantly worse (p < .01) compared to the rest of the patients. CONCLUSIONS:
Long-term outcome in WD is influenced by patient's compliance and neurological
comorbidity.
PMID- 29331562
TI - NADPH oxidases 2 activation in patients with Parkinson's disease.
PMID- 29331563
TI - Trends in Premature Mortality Due to Heart Failure by Autonomous Community in
Spain: 1999 to 2013.
AB - INTRODUCTION AND OBJECTIVES: Heart failure (HF) is a major public health problem,
and the prevalence increases with age. In Spain, there are considerable
differences between autonomous communities. The aim of this study was to analyze
trends in premature mortality due to HF between 1999 and 2013 in Spain by
autonomous community. METHODS: We analyzed data on mortality due to HF in Spanish
residents aged 0 to 75 years by autonomous community between 1999 and 2013. Data
were collected from files provided by the Spanish Statistics Office. Age-adjusted
mortality rates were analyzed and the average annual percentage rate was
estimated by Poisson models. RESULTS: Mortality due to HF represented 10.9% of
total mortality. In 2013, the national age-adjusted rate was 2.98 deaths in men
and 1.29 deaths in women per 100 000 inhabitants, with an annual mean reduction
of 2.27% and 4.53%, respectively. In men, average mortality showed the greatest
reduction in Castile-La-Mancha (6.30%). In Cantabria, average mortality
significantly increased (3.97%). In women, average mortality showed the greatest
decrease in the Chartered Community of Navarre (15.17%). CONCLUSIONS: During the
study period, mortality due to HF showed an overall average decrease, both
nationally and by autonomous community. This decrease was more pronounced in
women than in men. Premature mortality significantly decreased in most-but not
all-autonomous communities.
PMID- 29331564
TI - Direct renin inhibition is not enough to prevent reactive oxygen species
generation and vascular dysfunction in renovascular hypertension.
AB - Renin-angiotensin system activation promotes oxidative stress and endothelial
dysfunction. However, no previous study has examined the effects of the renin
inhibitor aliskiren, either alone or combined with angiotensin II type 1
antagonists on alterations induced by two-kidney, one-clip (2K1C) hypertension.
We compared the vascular effects of aliskiren (50mg/kg/day), losartan
(10mg/kg/day), or both by gavage for 4 weeks in 2K1C and control rats. Treatment
with losartan, aliskiren, or both exerted similar antihypertensive effects.
Aliskiren lowered plasma Ang I concentrations in sham rats and in hypertensive
rats treated with aliskiren or with both drugs. Aliskiren alone or combined with
losartan decreased plasma angiotensin II concentrations measured by high
performance liquid chromatography, whereas losartan alone had no effects. In
contrast, losartan alone or combined with aliskiren abolished hypertension
induced increases in aortic angiotensin II concentrations, whereas aliskiren
alone exerted no such effects. While hypertension enhanced aortic oxidative
stress assessed by dihydroethidium fluorescence and by lucigenin
chemiluminescence, losartan alone or combined with aliskiren, but not aliskiren
alone, abolished this alteration. Hypertension impaired aortic relaxation induced
by acetylcholine, and losartan alone or combined with aliskiren, but not
aliskiren alone, reversed this alteration. Losartan alone or combined with
aliskiren, but not aliskiren alone, increased plasma nitrite concentrations in
2K1C rats. These findings show that antihypertensive effects of aliskiren do not
prevent hypertension-induced vascular oxidative stress and endothelial
dysfunction. These findings contrast those found with losartan and suggest that
renin inhibition is not enough to prevent hypertension-induced impaired redox
biology and vascular dysfunction.
PMID- 29331565
TI - Saroglitazar reduces obesity and associated inflammatory consequences in murine
adipose tissue.
AB - Prevailing knowledge links chronic low-grade inflammation in the adipose tissue
to obesity and its associated metabolic complications. In this study, we
evaluated immunometabolic effects of a recently launched dual peroxisome
proliferator-activated receptor (PPAR) alpha & gamma agonist 'Saroglitazar' in a
mouse model of diet-induced obesity (DIO). Body composition analysis revealed
that saroglitazar treatment promoted hepatic weight gain, while attenuated
epididymal white adipose tissue (eWAT) mass in DIO. In the eWAT of saroglitazar
treated mice, histological analysis showed reduced adipocyte hypertrophy and
matrix deposition (picrosirius red staining). Immunological profiling of stromal
vascular fraction isolated from eWAT showed decreased pro-inflammatory cells (M1
macrophages, CD4 and CD8 T-cells) and increased anti-inflammatory M2 macrophages.
Gene expression and western blot analysis suggested that saroglitazar promoted
energy expenditure machinery and attenuated inflammatory as well as fibrotic
markers in eWAT during DIO. In conclusion, for the first time we are reporting
immunometabolic effects of dual PPARalpha & gamma agonist saroglitazar in DIO and
insulin resistance (IR). Saroglitazar exerted its beneficial effects on adipose
tissue by limiting, diet-induced adipose tissue dysfunction, adipocyte
hypertrophy, adipocyte cell damage and extracellular matrix deposition in
obesity.
PMID- 29331566
TI - Editorial Comment.
PMID- 29331567
TI - Author Reply.
PMID- 29331569
TI - Salinivibrio kushneri sp. nov., a moderately halophilic bacterium isolated from
salterns.
AB - Ten Gram-strain-negative, facultatively anaerobic, moderately halophilic
bacterial strains, designated AL184T, IB560, IB563, IC202, IC317, MA421, ML277,
ML318, ML328A and ML331, were isolated from water ponds of five salterns located
in Spain. The cells were motile, curved rods and oxidase and catalase positive.
All of them grew optimally at 37 degrees C, at pH 7.2-7.4 and in the presence of
7.5% (w/v) NaCl. Based on phylogenetic analyses of the 16S rRNA, the isolates
were most closely related to Salinivibrio sharmensis BAGT (99.6-98.2% 16S rRNA
gene sequence similarity) and Salinivibrio costicola subsp. costicola ATCC 35508T
(99.0-98.1%). According to the MLSA analyses based on four (gyrB, recA, rpoA and
rpoD) and eight (ftsZ, gapA, gyrB, mreB, pyrH, recA, rpoA and topA) concatenated
gene sequences, the most closely relatives were S. siamensis JCM 14472T (96.8
95.4% and 94.9-94.7%, respectively) and S. sharmensis DSM 18182T (94.0-92.6% and
92.9-92.7%, respectively). In silico DNA-DNA hybridization (GGDC) and average
nucleotide identity (ANI) showed values of 23.3-44.8% and 80.2-91.8%,
respectively with the related species demonstrating that the ten isolates
constituted a single novel species of the genus Salinivibrio. Its pangenome and
core genome consist of 6041 and 1230 genes, respectively. The phylogeny based on
the concatenated orthologous core genes revealed that the ten strains form a
coherent phylogroup well separated from the rest of the species of the genus
Salinivibrio. The major cellular fatty acids of strain AL184T were C16:0 and
C18:1. The DNA G+C content range was 51.9-52.5mol% (Tm) and 50.2-50.9mol%
(genome). Based on the phylogenetic-phylogenomic, phenotypic and chemotaxonomic
data, the ten isolates represent a novel species of the genus Salinivibrio, for
which the name Salinivibrio kushneri sp. nov. is proposed. The type strain is
AL184T (=CECT 9177T=LMG 29817T).
PMID- 29331568
TI - Overall survival and oncological outcomes after partial nephrectomy and radical
nephrectomy for cT2a renal tumors: A collaborative international study from the
French kidney cancer research network UroCCR.
AB - BACKGROUND: Partial nephrectomy (PN) is recommended as first-line treatment for
cT1 stage kidney tumors because of a better renal function and probably a better
overall survival than radical nephrectomy (RN). For larger tumors, PN has a
controversial position due to lack of evidence showing good cancer control. The
aim of this study was to compare the results of PN and RN in cT2a stage on
overall survival and oncological results. METHOD: A retrospective international
multicenter study was conducted in the frame of the French kidney cancer research
network (UroCCR). We considered all patients aged>=18 years who underwent
surgical treatment for localized renal cell carcinoma (RCC) stage cT2a (7.1-10cm)
between 2000 and 2014. Cox and Fine-Gray models were performed to analyze overall
survival (OS), cancer specific survival (CSS) and cancer-free survival (CFS).
Comparison between PN and RN was realized after an adjustment by propensity score
considering predefined confounding factors: age, sex, tumor size, pT stage of the
TNM classification, histological type, ISUP grade, ASA score. RESULTS: A total of
267 patients were included. OS at 3 and 5 years was 93.6% and 78.7% after PN and
88.0% and 76.2% after RN, respectively. CSS at 3 and 5 years was 95.4% and 80.2%
after PN and 91.0% and 85.0% after RN. No significant difference between groups
was found after propensity score adjustment for OS (HR 0.87, 95% CI: 0.37-2.05,
P=0.75), CSS (HR 0.52, 95% CI: 0.18-1.54, P=0.24) and CFS (HR 1.02, 95% CI: 0.50
2.09, P=0.96). CONCLUSION: PN seems equivalent to RN for OS, CSS and CFS in cT2a
stage kidney tumors. The risk of recurrence is probably more related to
prognostic factors than the surgical technique. The decision to perform a PN
should depend on technical feasibility rather than tumor size, both to imperative
and elective situation. LEVEL OF EVIDENCE: 4.
PMID- 29331570
TI - Meningeal marginal zone B-cell lymphoma: The meningioma trap.
AB - OBJECTIVE: To report a case of marginal zone MALT lymphoma of the temporal dura
mater, initially mistaken for temporal meningioma. CASE REPORT: A 60-year-old
immunocompetent woman, followed for more than 10 years for temporal meningioma
causing vertigo and mixed hearing loss, presented with cervical lymphadenopathy,
revealing marked progression of an intracranial lesion, leading to a diagnosis of
marginal zone MALT lymphoma based on histological examination of a cervical lymph
node. Treatment with 6 cycles of rituximab and bendamustine allowed complete
remission of cervical lymph node and intracranial lesions, confirming the
diagnosis of temporal dural mater lymphoma. CONCLUSION: Primary dural lymphoma
must be part of the differential diagnosis of meningioma. Long-term follow-up
allows correction of the diagnosis.
PMID- 29331571
TI - Interdepartmental imaging protocol for clinically based three-dimensional
computed tomography can provide accurate measurement of glenoid version.
AB - BACKGROUND: Conventional computed tomography (CT) is not accurate for glenoid
version measurement. This study sought to examine the feasibility of an
interdepartmental protocol implemented between orthopedic surgery and radiology
departments for acquisition of anatomic axial CT images and to validate the
glenoid version measured through such a protocol. MATERIALS AND METHODS: Data of
30 conventional CT scans of 10 normal and 20 osteoarthritic glenoids were
transferred to clinical 3-dimensional imaging software by a radiology technician
trained for the study. The technician independently reoriented the scapulae to
generate anatomic CT images. A separate team of orthopedic researchers used
laboratory-based 3-dimensional reconstruction software (Mimics; Materialise,
Leuven, Belgium) to generate anatomic axial images. Three independent examiners
measured glenoid version on the conventional CT, reoriented anatomic CT, and
Mimics images at the superior, middle, and inferior levels. Data were analyzed
using the Mimics data as the "gold standard." RESULTS: Reoriented anatomic CT
images generated by the technician resulted in almost identical version
measurements to the Mimics images in both normal and arthritic glenoids. The
conventional CT images had poor agreement with the Mimics images in normal
glenoids but had good agreement in arthritic glenoids. Both normal and arthritic
glenoids had increased retroversion superiorly (P < .05), and this phenomenon was
significantly exaggerated on the conventional CT images (P < .05). CONCLUSIONS:
This study demonstrated that an interdepartmental protocol can produce reoriented
anatomic axial CT images on which true glenoid version can be accurately
measured. Such an institutional protocol would help surgeons accurately evaluate
glenoid version preoperatively with reduced workload and expense.
PMID- 29331572
TI - Comments on "Low-dose-rate prostate brachytherapy: 4-8 week postimplant prostate
specific antigen a novel predictor of biochemical failure-free survival".
PMID- 29331573
TI - Deformable image registration-based contour propagation yields clinically
acceptable plans for MRI-based cervical cancer brachytherapy planning.
AB - PURPOSE: To study the dosimetric impact of deformable image registration-based
contour propagation on MRI-based cervical cancer brachytherapy planning. METHODS
AND MATERIALS: High-risk clinical target volume (HRCTV) and organ-at-risk (OAR)
contours were delineated on MR images of 10 patients who underwent ring and
tandem brachytherapy. A second set of contours were propagated using a
commercially available deformable registration algorithm. "Manual-contour" and
"propagated-contour" plans were optimized to achieve a maximum dose to the most
minimally exposed 90% of the volume (D90) (%) of 6 Gy/fraction, respecting
minimum dose to the most exposed 2cc of the volume (D2cc) OAR constraints of 5.25
Gy and 4.2 Gy/fraction for bladder and rectum/sigmoid (86.5 and 73.4 Gy
equivalent dose in 2 Gy fractions [EQD2] for external beam radiotherapy [EBRT] +
brachytherapy, respectively). Plans were compared using geometric and dosimetric
(total dose [EQD2] EBRT + brachytherapy) parameters. RESULTS: The differences
between the manual- and propagated-contour plans with respect to the HRCTV D90
and bladder, rectum, and sigmoid D2cc were not statistically significant (per
fraction basis). For the EBRT + brachytherapy course, the D2cc delivered to the
manually contoured OARs by the propagated-contour plans ranging 98-107%, 95-105%,
and 92-108% of the dose delivered by the manual-contour plans (max 90.4, 70.3,
and 75.4 Gy for the bladder, rectum, and sigmoid, respectively). The HRCTV dose
in the propagated-contour plans was 97-103% of the dose in the manual-contour
plans (maximum difference 2.92 Gy). Increased bladder filling resulted in
increased bladder dose in manual- and propagated-contour plans. CONCLUSIONS: When
deformable image registration-propagated contours are used for cervical
brachytherapy planning, the HRCTV dose is similar to the dose delivered by manual
contour plans and the doses delivered to the OARs are clinically acceptable,
suggesting that our algorithm can replace manual contouring for appropriately
selected cases that lack major interfractional anatomical changes.
PMID- 29331574
TI - A Medicare cost analysis of MRI- versus CT-based high-dose-rate brachytherapy of
the cervix: Can MRI-based planning be less costly?
AB - PURPOSE: While some institutions deliver multiple fractions per implant for MRI
based planning, it is common for only one fraction to be delivered per implant
with CT-based cervical brachytherapy. The purpose of this study was to compare
physician costs, hospital costs, and overall costs for cervical cancer patients
treated with either CT-based or MRI-based high-dose-rate (HDR) cervical
brachytherapy to determine if MRI-based brachytherapy as described can be
financially feasible. METHODS AND MATERIALS: We identified 40 consecutive
patients treated with curative intent cervical brachytherapy. Twenty patients
underwent CT-based HDR brachytherapy with five fractions delivered in five
implants on nonconsecutive days in an outpatient setting with the first implant
placed with a Smit sleeve under general anesthesia. Twenty patients received MRI
based HDR brachytherapy with four fractions delivered in two implants, each with
MRI-based planning, performed 1-2 weeks apart with an overnight hospital
admission for each implant. We used Medicare reimbursements to assess physician
costs, hospital costs, and overall cost. RESULTS: The median cost of MRI-based
brachytherapy was $14,248.75 (interquartile range [IQR]: $13,421.32-$15,539.74),
making it less costly than CT-based brachytherapy with conscious sedation (i.e.,
$18,278.85; IQR: $17,323.13-$19,863.03, p < 0.0001) and CT-based brachytherapy
with deep sedation induced by an anesthesiologist (i.e., $27,673.44; IQR:
$26,935.14-$29,511.16, p < 0.0001). CT-based brachytherapy with conscious
sedation was more costly than CT-based brachytherapy with deep sedation (p <
0.001). CONCLUSIONS: MRI-based brachytherapy using the described treatment course
was less costly than both methods of CT-based brachytherapy. Cost does not need
to be a barrier for MRI-based cervical brachytherapy, especially when delivering
multiple fractions with the same application.
PMID- 29331575
TI - Validation of MRI to TRUS registration for high-dose-rate prostate brachytherapy.
AB - PURPOSE: The objective of this study was to develop and validate an open-source
module for MRI to transrectal ultrasound (TRUS) registration to support tumor
targeted prostate brachytherapy. METHODS AND MATERIALS: In this study, 15
patients with prostate cancer lesions visible on multiparametric MRI were
selected for the validation. T2-weighted images with 1-mm isotropic voxel size
and diffusion weighted images were acquired on a 1.5T Siemens imager. Three
dimensional (3D) TRUS images with 0.5-mm slice thickness were acquired. The
investigated registration module was incorporated in the open-source 3D Slicer
platform, which can compute rigid and deformable transformations. An extension of
3D Slicer, SlicerRT, allows import of and export to DICOM-RT formats. For
validation, similarity indices, prostate volumes, and centroid positions were
determined in addition to registration errors for common 3D points identified by
an experienced radiation oncologist. RESULTS: The average time to compute the
registration was 35 +/- 3 s. For the rigid and deformable registration,
respectively, Dice similarity coefficients were 0.87 +/- 0.05 and 0.93 +/- 0.01
while the 95% Hausdorff distances were 4.2 +/- 1.0 and 2.2 +/- 0.3 mm. MRI
volumes obtained after the rigid and deformable registration were not
statistically different (p > 0.05) from reference TRUS volumes. For the rigid and
deformable registration, respectively, 3D distance errors between reference and
registered centroid positions were 2.1 +/- 1.0 and 0.4 +/- 0.1 mm while
registration errors between common points were 3.5 +/- 3.2 and 2.3 +/- 1.1 mm.
Deformable registration was found significantly better (p < 0.05) than rigid
registration for all parameters. CONCLUSIONS: An open-source MRI to TRUS
registration platform was validated for integration in the brachytherapy
workflow.
PMID- 29331576
TI - Normative distribution of substance P and its tachykinin neurokinin-1 receptor in
the medullary serotonergic network of the human infant during postnatal
development.
AB - Substance P (SP) and its tachykinin NK1 receptor (NK1R) function within key
medullary nuclei to regulate cardiorespiratory and autonomic control. We examined
the normative distribution of SP and NK1R in the serotonergic (5
Hydroxytryptamine, [5-HT]) network of the human infant medulla during postnatal
development, to provide a baseline to facilitate future analysis of the SP/NK1R
system and its interaction with 5-HT within pediatric brainstem disorders in
early life. [125I] labelled Bolton Hunter SP (BH-SP) tissue receptor
autoradiography (n = 15), single label immunohistochemistry (IHC) and double
label immunofluorescence (IF) (n = 10) were used to characterize the normative
distribution profile of SP and NK1R in the 5-HT network of the human infant
medulla during postnatal development. Tissue receptor autoradiography revealed
extensive distribution of SP and NK1R in nuclei intimately related to
cardiorespiratory function and autonomic control, with significant co
distribution and co-localization with 5-HT in the medullary network in the normal
human infant during development. A trend for NK1R binding to decrease with age
was observed with significantly higher binding in premature and male infants. We
provide further evidence to suggest a significant role for SP/NK1R in the early
postnatal period in the modulation of medullary cardiorespiratory and autonomic
control in conjunction with medullary 5-HT mediated pathways and provide a
baseline for future analysis of the potential consequences of abnormalities in
these brainstem neurotransmitter networks during development.
PMID- 29331577
TI - A novel encystation specific protein kinase regulates chitin synthesis in
Entamoeba invadens.
AB - Phosphorylation is an important post-translational modification of proteins and
is involved in the regulation of a variety of cellular events. The proteome of
Entamoeba invadens, the reptilian counterpart of Entamoeba histolytica consists
of an overwhelming number of putative protein kinases, and some may have a role
to play in Entamoeba encystation. In this study, we have identified a novel
protein kinase named as EiCSpk (Entamoeba invadenscyst specific protein kinase)
which expressed almost exclusively during encystation. It is an active Protein
kinase C with a characteristic substrate phosphorylation and auto-phosphorylation
property. Gene silencing study has unveiled its role as a regulator of chitin
synthesis through transcriptional activation of the chitin synthesis pathway
genes along with glycogen phosphorylases that are involved in the influx of
glucose from glycogen breakdown for chitin synthesis.
PMID- 29331579
TI - Corrections.
PMID- 29331578
TI - Molecular detection and characterisation of Babesia and Theileria in Australian
hard ticks.
AB - Babesia and Theileria are intraerythrocytic protozoans of the phylum Apicomplexa.
These species are capable of infecting wild and domestic animals and have
historically caused great economic loss in the agricultural industry. In recent
years human babesiosis has been deemed an emerging zoonosis in North America,
Europe and Asia. The first locally acquired case of babesiosis in Australia,
caused by Babesia microti, was reported in March 2012. A number of native Babesia
and Theileria species have been identified in Australian marsupials, however
their associated tick vectors and threat to human health is unknown. In the
present study DNA was extracted from 1154 ticks collected from across Australia.
PCR was used to amplify a Babesia and Theileria-specific partial region of the
18S ribosomal RNA gene. Positive samples were sequenced and phylogenetic analysis
was performed. Twenty-nine sequences were obtained from ticks belonging to the
genera Ixodes, Haemaphysalis and Bothriocroton. The sequences were closely
related to Babesia macropus, and Theileria recently identified in marsupials and
monotremes. Bayesian inference and maximum likelihood methods showed that
Australian Babesia and Theileria species form monophyletic groups.
PMID- 29331580
TI - Local delivery of mometasone furoate from an eluting endotracheal tube.
AB - Laryngeal and tracheal morbidity is a common complication of endotracheal tube
(ETT)-based airway management, and manifests as local irritation, inflammation,
and edema. Systemic corticosteroids are commonly administered to manage these
conditions; however, their efficacy is inadequate and limited by potential severe
side effects. In the present study, a steroid delivery system for local therapy
was developed to generate relatively high local drug concentrations and to
improve drug efficacy. ETTs were coated with electrospun poly (lactic-co-glycolic
acid) (PLGA) nanofibers loaded with mometasone furoate (MF), creating a
microscale thick layer. MF exhibited sustained release from coated ETTs over
14days in vitro. An in vivo efficacy study in rats demonstrated the therapeutic
benefit of MF-coated ETTs over bare ETTs, as measured by reduced laryngeal
mucosal thickness and submucosal laryngeal edema. The fiber coating remained
intact during tube intubation and extubation, demonstrating good adhesion to the
tubes even after 24h in aqueous solution at 37 degrees C. These findings
demonstrate the potential of drug-loaded ETTs to revolutionize the standard of
care for endotracheal intubation.
PMID- 29331581
TI - Identification and characterization of arginine finger-like motifs, and endosome
lysosome basolateral sorting signals within the Coxiella burnetii type IV
secreted effector protein CirA.
AB - Coxiella burnetii is an obligate intracellular pathogen that replicates in an
endolysosome-like compartment termed the Coxiella-containing vacuole (CCV).
Formation of this unique replicative niche requires delivery of bacterial
effector proteins into the host cytosol where they mediate crucial interactions
with the host. We previously identified an essential Dot/Icm effector, CirA that
is required for intracellular replication and CCV formation. Furthermore, CirA
was shown to stimulate the GTPase activity of RhoA in vitro. In the current
study, we used a bioinformatics-guided approach and identified three arginine
finger-like motifs, often found in Rho GTPase-activating proteins (GAPs) and
endosome-lysosome basolateral sorting signals associated with vesicle
trafficking. When expressed in mammalian cells, mutation of either endosome
lysosome-basolateral sorting signals or the arginine finger-like motifs rescued
stress phenotypes and decreased plasma membrane localization of ectopically
expressed CirA. We further demonstrate that endosome-lysosome sorting signals are
required for co-localization with Rab5 and Rab7. Collectively our data indicate
that arginine finger-like motifs and endosome-lysosome-basolateral sorting
signals within CirA are essential for interaction with the host cytoskeleton.
PMID- 29331582
TI - Inositol polyphosphates contribute to cellular circadian rhythms: Implications
for understanding lithium's molecular mechanism.
AB - Most living organisms maintain cell autonomous circadian clocks that synchronize
critical biological functions with daily environmental cycles. In mammals, the
circadian clock is regulated by inputs from signaling pathways including glycogen
synthase kinase 3 (GSK3). The drug lithium has actions on GSK3, and also on
inositol metabolism. While it is suspected that lithium's inhibition of GSK3
causes rhythm changes, it is not known if inositol polyphosphates can also affect
the circadian clock. We examined whether the signaling molecule inositol
hexaphosphate (IP6) has effects on circadian rhythms. Using a bioluminescent
reporter (Per2::luc) to measure circadian rhythms, we determined that IP6
increased rhythm amplitude and shortened period in NIH3T3 cells. The IP6 effect
on amplitude was attenuated by selective siRNA knockdown of GSK3B and
pharmacological blockade of AKT kinase. However, unlike lithium, IP6 did not
induce serine-9 phosphorylation of GSK3B. The synthesis of IP6 involves the
enzymes inositol polyphosphate multikinase (IPMK) and inositol pentakisphosphate
2-kinase (IPPK). Knockdown of Ippk had effects opposite to those of IP6,
decreasing rhythm amplitude and lengthening period. Ipmk knockdown had few
effects on rhythm alone, but attenuated the effects of lithium on rhythms.
However, lithium did not change the intracellular content of IP6 in NIH3T3 cells
or neurons. Pharmacological inhibition of the IP6 kinases (IP6K) increased rhythm
amplitude and shortened period, suggesting secondary effects of inositol
pyrophosphates may underlie the period shortening effect, but not the amplitude
increasing effect of IP6. Overall, we conclude that inositol phosphates, in
particular IP6 have effects on circadian rhythms. Manipulations affecting IP6 and
related inositol phosphates may offer a novel means through which circadian
rhythms can be regulated.
PMID- 29331583
TI - Importins alpha and beta signaling mediates endothelial cell inflammation and
barrier disruption.
AB - Nucleocytoplasmic shuttling via importins is central to the function of
eukaryotic cells and an integral part of the processes that lead to many human
diseases. In this study, we addressed the role of alpha and beta importins in the
mechanism of endothelial cell (EC) inflammation and permeability, important
pathogenic features of many inflammatory diseases such as acute lung injury and
atherosclerosis. RNAi-mediated knockdown of importin alpha4 or alpha3 each
inhibited NF-kappaB activation, proinflammatory gene (ICAM-1, VCAM-1, and IL-6)
expression, and thereby endothelial adhesivity towards HL-60 cells, upon thrombin
challenge. The inhibitory effect of alpha4 and alpha3 knockdown was associated
with impaired nuclear import and consequently, DNA binding of RelA/p65 subunit of
NF-kappaB and occurred independently of IkappaBalpha degradation. Intriguingly,
knockdown of importins alpha4 and alpha3 also inhibited thrombin-induced RelA/p65
phosphorylation at Ser536, showing a novel role of alpha importins in regulating
transcriptional activity of RelA/p65. Similarly, knockdown of importin beta1, but
not beta2, blocked thrombin-induced activation of RelA/p65 and its target genes.
In parallel studies, TNFalpha-mediated inflammatory responses in EC were
refractory to knockdown of importins alpha4, alpha3 or beta1, indicating a
stimulus-specific regulation of RelA/p65 and EC inflammation by these importins.
Importantly, alpha4, alpha3, or beta1 knockdown also protected against thrombin
induced EC barrier disruption by inhibiting the loss of VE-cadherin at adherens
junctions and by regulating actin cytoskeletal rearrangement. These results
identify alpha4, alpha3 and beta1 as critical mediators of EC inflammation and
permeability associated with intravascular coagulation.
PMID- 29331585
TI - Cathepsin L promotes ionizing radiation-induced U251 glioma cell migration and
invasion through regulating the GSK-3beta/CUX1 pathway.
AB - Cathepsin L (CTSL) is a lysosomal cysteine protease overexpressed and secreted by
tumor cells. Our previous study found that CTSL was involved in ionizing
radiation (IR)-induced epithelial-mesenchymal transition (EMT) and the increase
of glioma invasion and migration. However, the mechanisms by which CTSL promoted
this IR-induced glioma migration and invasion remained unclear. In this study, we
demonstrated that IR reduced glycogen synthase kinase-3beta (GSK-3beta) activity,
via the CTSL-mediated phosphorylation of its serine-9 residue, in U251 cells.
Moreover, inhibition of p-GSK-3betaSer9 in overexpressing CTSL cells attenuated
EMT and decreased the expression of snail, an EMT-related transcription factor.
As a result, U251 cell migration and invasion was inhibited compared to over-CTSL
cells. Alternatively, when CTSL was activated by IR or exogenously overexpressed,
CTSL promoted EMT by processing homeobox protein cut-like1 (CUX1) to produce the
physiologically active p110 isoform. In brief, this study revealed that IR
induced EMT as well as migration and invasion of glioma cells are mediated by
CTSL through the Akt/GSK-3beta/snail and CUX1 pathways. Consequently, this
research also led to the identification of a potential novel target for
therapeutic intervention of glioma.
PMID- 29331586
TI - Positive effects of total recovery period on anti- and pro-inflammatory cytokines
are not linked to performance re-establishment in overtrained mice.
AB - The association between excessive training sessions (i.e., overtraining/OT) and
periods of inadequate recovery is linked to the nonfunctional overreaching (NFOR)
state, which is defined as an unexplained decrement or stagnation of performance.
The cytokine hypothesis of OT considers that pro-inflammatory cytokines are
responsible by the NFOR state-induced performance decrement. Investigations using
rodent models of OT verified increased levels of pro-inflammatory cytokines in
hypothalamus, liver, serum and skeletal muscle samples. Recently, our research
group observed that a 2-week total recovery period was not able to re-establish
the NFOR state-induced performance decrement. As the responses of anti- and pro
inflammatory cytokines were not measured, we aimed to investigate the effects of
2-week total recovery period on the protein contents of IL-1beta, IL-6, IL-10, IL
15, TNF-alpha and SOCS-3 in serum and skeletal muscle samples of overtrained
mice. Also, a bioinformatics analysis was performed to investigate the
correlations of IL-1beta, IL-6, IL-10, IL-15, TNF-alpha and SOCS-3 in skeletal
muscle with locomotor activity. In summary, the 2-week total recovery period
upregulated the anti-inflammatory cytokines and normalized the pro-inflammatory
cytokines without a concomitant re-establishment of performance.
PMID- 29331587
TI - IL-23/IL-17 immune axis in Guillain Barre Syndrome: Exploring newer vistas for
understanding pathobiology and therapeutic implications.
AB - Guillain Barre Syndrome (GBS) is a severe disorder of the peripheral nervous
system with an inadequately known etiopathology. It is a post infectious immune
mediated disorder, characterized by autoantibody production, complement
activation as well as T reactivity against gangliosides. However, the precise
etiopathogenesis remains poorly understood in a majority of the patients. Th17
cells, a recently identified lineage of Th cells have emerged as a predominant
inducer of autoimmunity and inflammation in various immunological disorders.
Pathobiological role of Th17 pathway is also becoming increasingly apparent in
the nervous system disorders. Two cytokines, such as IL-23, known to determine
the pathogenic potential of Th17 cells and IL-17, a prototype effector cytokine
of Th17 pathway can form IL-23/IL-17 immune axis. Aberrant functioning of this
immune axis has been implicated in many autoimmune diseases. Therapeutic
strategies that potentially target this immune axis have shown encouraging
results in diseases with immunological underpinnings. Preliminary data obtained
both from animal and clinical studies indicate a possible role of this immune
axis in GBS. Herein, we explore and highlight the relevance and functional
implications of IL-23/IL-17 immune axis in GBS. Understanding this immune axis
may shed important insights into the etiology and treatment of GBS.
PMID- 29331588
TI - Antagonism of cysteinyl leukotriene receptor 1 (cysLTR1) by montelukast
suppresses cell senescence of chondrocytes.
AB - Aging is closely associated with osteoarthritis (OA). Although its underlying
mechanisms remain unknown, cellular senescence in chondrocytes has become an
important therapeutic target for the treatment of OA. Cysteinyl leukotriene
receptors (cysLTRs) mediate the pathobiological function of cysteinyl
leukotrienes (cysLTs). However, the roles of cysLTRs in the pathogenesis of OA
have not been reported before. In the current study, we found that cysLTR1 but
not cysLTR2 is expressed in human primary chondrocytes. In addition, stimulation
with tumor necrosis factor alpha (TNF-alpha) resulted in a significant increase
in the expression of cysLTR1. Interestingly, montelukast, a specific cysLTR1
antagonist, attenuated TNF-alpha-induced up-regulation of the activity of
senescence-associated beta-galactosidase (SA-beta-Gal). In addition, TNF-alpha
led to cell cycle arrest at the G0/G1 phase, which was prevented by treatment
with montelukast. Notably, montelukast reduced expression of the senescence
markers p53, p21 and PAI-1. In addition, montelukast ameliorated TNF-alpha
induced K382 acetylation of p53 by promoting the expression of SIRT1. Silencing
of SIRT1 using SIRT1 siRNA broke the inhibitory effects of montelukast on K382
acetylation of p53. Importantly, silencing of cysLTR1 reversed the reduction of
SIRT1 expression as well as the K382 acetylation of p53. Our findings strongly
implicate that cysLTR1 has the capacity to regulate cellular senescence in
chondrocytes. It is suggested that montelukast may be a potential therapeutic
agent for chondro-protective therapy.
PMID- 29331584
TI - Protein neddylation and its alterations in human cancers for targeted therapy.
AB - Neddylation, a post-translational modification that conjugates an ubiquitin-like
protein NEDD8 to substrate proteins, is an important biochemical process that
regulates protein function. The best-characterized substrates of neddylation are
the cullin subunits of Cullin-RING ligases (CRLs), which, as the largest family
of E3 ubiquitin ligases, control many important biological processes, including
tumorigenesis, through promoting ubiquitylation and subsequent degradation of a
variety of key regulatory proteins. Recently, increasing pieces of experimental
evidence strongly indicate that the process of protein neddylation modification
is elevated in multiple human cancers, providing sound rationale for its
targeting as an attractive anticancer therapeutic strategy. Indeed, neddylation
inactivation by MLN4924 (also known as pevonedistat), a small molecule inhibitor
of E1 NEDD8-activating enzyme currently in phase I/II clinical trials, exerts
significant anticancer effects by inducing cell cycle arrest, apoptosis,
senescence and autophagy in a cell-type and context dependent manner. Here, we
summarize the latest progresses in the field with a major focus on preclinical
studies in validation of neddylation modification as a promising anticancer
target.
PMID- 29331589
TI - The iridocorneal endothelial syndrome.
AB - The iridocorneal endothelial syndrome represents a unique group of ocular
pathologies (Chandler syndrome, progressive iris atrophy, and Cogan-Reese
syndrome) characterized by the proliferation of corneal endothelial cells that
migrate toward the iridocorneal angle and iris surface causing, to a degree
varying according to the subtype, corneal edema and decompensation and secondary
glaucoma, whether by obstructing the angle or producing peripheral anterior
synechiae by contraction of the basement membrane of the migrating cells over the
surface of the iris. A triggering factor, possibly viral, induces the corneal
endothelial cells to proliferate and behave like epithelial cells. Diagnosis is
made based on typical ocular findings on the cornea and iris. Iridocorneal
endothelial syndrome is more frequent in young women, with unilateral involvement
in most cases. In vivo confocal microscopy is an excellent diagnostic tool,
especially in borderline presentations like early cases of Chandler syndrome,
which affects the cornea predominantly. Typical clinical management consists of
treating the corneal edema and decompensation, where endothelial keratoplasty
techniques have replaced in many cases the need for a penetrating keratoplasty
and treating the secondary glaucoma, which usually requires surgical
intervention.
PMID- 29331590
TI - Setting mechanism of a new injectable Dicalcium Phosphate Dihydrate (DCPD)
forming cement.
AB - We previously described the gelation mechanism of calcium polyphosphate (CPP) in
the presence of water. In this study, we developed novel and injectable poly
dicalcium phosphate dihydrate (P-DCPD) forming cement by the reaction of acidic
CPP gel with alkali tetracalcium phosphate (TTCP). The setting reaction mechanism
of P-DCPD is due to the intermolecular interaction between CPP gel and TTCP that
was supported by XRD, AFM, Raman spectra analysis and SEM. The setting mechanism
of P-DCPD is completely different from the classical calcium phosphate cement
(CPC) that achieves crystallization by monophosphates reaction. P-DCPD represents
a new type of poly-CPCs with significant advantages, including strong mechanical
strength, excellent cohesion and easy of handling. More extensive experiments are
currently underway to further evaluate the performance of P-DCPD cements,
including biocompatibility, degradation behavior and bone defect hearing
efficacy, among others.
PMID- 29331593
TI - Latent class analysis of the health of the nation outcome scales: A comparison of
Swiss and English profiles and exploration of their predictive utility.
PMID- 29331592
TI - Combined creatinine-cystatin C CKD-EPI equation significantly underestimates
measured glomerular filtration rate in people with type 2 diabetes mellitus.
AB - AIM: To evaluate the accuracy of creatinine and cystatin C (cysC) equations to
estimate glomerular filtration rate (GFR) in type 2 diabetes mellitus (DM)
patients and healthy adults. METHODS: Case-control study including 84 patients
with type 2 DM and 100 healthy adults with measured GFR (mGFR)>=60mL/min/1.73m2.
GFR was measured by 51Cr-EDTA and estimated (eGFR) by the following equations
using creatinine, cysC or both markers: Chronic Kidney Disease Epidemiology
Collaboration (CKD-EPI), Caucasian Asian Pediatrics and Adults (CAPA), CKD-EPI
creatinine-cystatin C (CKDEPI-CC), and CKD-EPI cystatin C (CKDEPIcysC). Agreement
was evaluated by Bland & Altman analysis. RESULTS: Healthy individuals were 66%
females, aged 38+/-14years; they presented mGFR 112+/-19mL/min/1.73m2 and eGFR by
CKD-EPI, CKDEPI-CC, CKDEPIcysC and CAPA equations, respectively, 108+/-17, 102+/
15, 97+/-16 and 93+/-16mL/min/1.73m2. DM group were 50% females, aged 59+/
19years and presented mGFR 104+/-27 and eGFR 87+/-19, 80+/-18, 74+/-20 and 73+/
18mL/min/1.73m2, respectively. All equations significantly underestimated mGFR,
excepting creatinine-based CKD-EPI in the healthy group. The performance was
considerably worse for GFRs above 120mL/min/1.73m2. CONCLUSION: In both healthy
and type 2 DM patients, cystatin C-based equations, including the combined CKD
EPI creatinine-cystatin equation, failed to improve the accuracy of GFR
estimation, especially for normal and high normal GFR values.
PMID- 29331591
TI - Brochosomins and other novel proteins from brochosomes of leafhoppers (Insecta,
Hemiptera, Cicadellidae).
AB - Brochosomes (BS) are secretory granules resembling buckyballs, produced
intracellularly in specialized glandular segments of the Malpighian tubules and
forming superhydrophobic coatings on the integuments of leafhoppers (Hemiptera,
Cicadellidae). Their composition is poorly known. Using a combination of SDS
PAGE, LC-MS/MS, next-generation sequencing (RNAseq) and bioinformatics we
demonstrate that the major structural component of BS of the leafhopper
Graphocephala fennahi Young is a novel family of 21-40-kDa secretory proteins,
referred to herein as brochosomins (BSM), apparently cross-linked by disulfide
bonds. At least 28 paralogous BSM were identified in a transcriptome assembly of
this species, most of which were detected in BS. Multiple additional BS
associated proteins (BSAP), possibly loosely attached to the outer and inner
surfaces of BS, were also identified; some of these were glycine-, tyrosine- and
proline-rich. BSM and BSAP together accounted for half of the 100 most expressed
transcripts in the Malpighian tubules of G. fennahi. Except for several minor
BSAP possibly related to cyclases, BSM and BSAP had no homologs among known
proteins, thus representing taxonomically restricted gene families (orphans).
Searching in 50 whole-body transcriptome assemblies of Hemiptera found homologs
of BSM in representatives of all five families of the superfamily Membracoidea
(Cicadellidae, Myerslopiidae, Aetalionidae, Membracidae, and Melizoderidae), but
not in other lineages. Among the identified proteins only BSM were shared in
common between all 17 surveyed leafhoppers known to produce BS. Combined CHN
elemental and aminoacid analyses estimated the total protein content of BS from
the integument of G. fennahi to be 60-70%.
PMID- 29331594
TI - Effects of physical activity on the symptoms of Tourette syndrome: A systematic
review.
AB - There is irrefutable evidence that routine physical activity or exercise can
offer considerable health benefits to individuals living with various mental
disorders. However, it is not clear what effect physical activity has on the
symptoms of Tourette syndrome. Despite a paucity of evidence, physical activity
or exercise has already been recommended by various health organizations for the
management of tics. We provide a systematic review of the effects of physical
activity or exercise on tic symptomology in individuals with Tourette syndrome.
Major electronic databases were searched for all available publications before
August 2017. Keywords and MeSH terms included "physical activity" or "exercise"
or "exercise therapy" or "physical exertion" or "sports" and "tics" or "tic
disorders" or "Tourette." Eight studies were included, the majority of which were
case reports. Despite a number of methodological limitations of the included
studies, the review points to a trend that the effects of acute physical activity
are intensity-dependent, where light intensity may alleviate and vigorous
intensity may exacerbate tics. Chronic physical activity, however, appears to
reduce the severity of tics even at higher intensity. Several physiological
mechanisms may explain the differential effects of acute and chronic physical
activity in Tourette syndrome. Future randomized controlled studies should better
characterize the effects of different intensities and types of physical activity
in Tourette syndrome.
PMID- 29331595
TI - The interaction between neurocognitive functioning, subthreshold psychotic
symptoms and pharmacotherapy in 22q11.2 deletion syndrome: A longitudinal
comparative study.
AB - BACKGROUND: The 22q11.2 deletion syndrome (22q11DS) is the most common genetic
syndrome associated with schizophrenia. The goal of this study was to evaluate
longitudinally the interaction between neurocognitive functioning, the presence
of subthreshold psychotic symptoms (SPS) and conversion to psychosis in
individuals with 22q11DS. In addition, we attempted to identify the specific
neurocognitive domains that predict the longitudinal evolution of positive and
negative SPS, as well as the effect of psychiatric medications on 22q11DS
psychiatric and cognitive developmental trajectories. METHODS: Forty-four
participants with 22q11DS, 19 with Williams syndrome (WS) and 30 typically
developing (TD) controls, age range 12-35years, were assessed at two time points
(15.2+/-2.1months apart). Evaluation included the Structured Interview for
Prodromal Symptoms (SIPS), structured psychiatric evaluation and the Penn
Computerized Neurocognitive Battery (CNB). RESULTS: 22q11DS individuals with SPS
had a yearly conversion rate to psychotic disorders of 8.8%, compared to none in
both WS and TD controls. Baseline levels of negative SPS were associated with
global neurocognitive performance (GNP), executive function and social cognition
deficits, in individuals with 22q11DS, but not in WS. Deficits in GNP predicted
negative SPS in 22q11DS and the emergence or persistence of negative SPS. 22q11DS
individuals treated with psychiatric medications showed significant improvement
in GNP score between baseline and follow-up assessments, an improvement that was
not seen in untreated 22q11DS. CONCLUSIONS: Our results highlight the time
dependent interplay among positive and negative SPS symptoms, neurocognition and
pharmacotherapy in the prediction of the evolution of psychosis in 22q11DS.
PMID- 29331596
TI - Problem-solving therapy for adult depression: An updated meta-analysis.
AB - BACKGROUND: Problem-solving therapy (PST) is one of the best examined types of
psychotherapy for adult depression. No recent meta-analysis has examined the
effects of PST compared to control groups or to other treatments. We wanted to
verify whether PST is effective, whether effects are comparable to those of other
treatments, and whether we could identify the possible sources of high
heterogeneity that was found in earlier meta-analyses. METHODS: We conducted
systematic searches in bibliographical databases, including PubMed, PsycInfo,
Embase and the Cochrane database of randomized trials. RESULTS: We included 30
randomized controlled trials on PST (with 3530 patients), in which PST was
compared to control conditions, with other therapies, and with pharmacotherapy.
We could compare these 30 trials on PST also with 259 trials on other
psychotherapies for adult depression. The effect size of PST versus control
groups was g=0.79 (0.57-1.01) with very high heterogeneity (I2=84; 95% CI: 77
88). The effect size from the 9 studies with low risk of bias was g=0.34 (95% CI:
0.22-0.46) with low heterogeneity (I2=32; 95% CI: 0-68), which is comparable to
the effects of other psychotherapies. PST was a little more effective than other
therapies in direct comparisons, but that may be explained by the considerable
number of studies with researcher allegiance towards PST. In meta-regression
analyses of all controlled studies, no significant difference between PST and
other therapies was found. CONCLUSION: PST is probably an effective treatment for
depression, with effect sizes that are small, but comparable to those found for
other psychological treatments of depression.
PMID- 29331597
TI - Variation of genes involved in oxidative and nitrosative stresses in depression.
AB - The dominating hypothesis among numerous hypotheses explaining the pathogenesis
of depressive disorders (DD) is the one involving oxidative and nitrosative
stress. In this study, we examined the association between single-nucleotide
polymorphisms of the genes encoding SOD2 (superoxide dismutase 2), CAT
(catalase), GPx4 (glutathione peroxidase 4), NOS1 (nitric oxide synthase 1), NOS2
(nitric oxide synthase 2), and the development of depressive disorders. Our study
was carried out on the DNA isolated from peripheral blood collected from 281
depressed patients and 229 controls. Using TaqMan probes, we genotyped the
following six polymorphisms: c.47T>C (p.Val16Ala) (rs4880) in SOD2, c.-89A>T
(rs7943316) in CAT, c.660T>C (rs713041) in GPx4, c.-420-34221G>A (rs1879417) in
NOS1, c.1823C>T (p.Ser608Leu) (rs2297518), and c.-227G>C (rs10459953) in NOS2. We
found that the T/T genotype of the c.47T>C polymorphism was linked with an
increased risk of depression. Moreover, the T/T genotype and T allele of c.660T>C
increased the risk of DD occurrence, while the heterozygote and C allele
decreased this risk. On the other hand, we discovered that the A/A genotype of c.
89A>T SNP was associated with a reduced risk of DD, while the A/T genotype
increased this risk. We did not find any correlation between the
genotypes/alleles of c.-420-34221G>A, c.1823C>T, and c.-227G>C, and the
occurrence of DD. In addition, gene-gene and haplotype analyses revealed that
combined genotypes and haplotypes were connected with the disease. Moreover, we
found that sex influenced the impact of some SNPs on the risk of depression.
Concluding, the studied polymorphisms of SOD2, CAT and GPx4 may modulate the risk
of depression. These results support the hypothesis that oxidative and
nitrosative stresses are involved in the pathogenesis of depressive disorders.
PMID- 29331598
TI - Commentary on "Motor system dysfunction in the schizophrenia diathesis: Neural
systems to neurotransmitters".
PMID- 29331599
TI - Long-term reduction of seclusion and forced medication on a hospital-wide level:
Implementation of an open-door policy over 6 years.
AB - BACKGROUND: Psychiatric inpatient treatment is increasingly performed in settings
with locked doors. However, locked wards have well-known disadvantages and are
ethically problematic. In addition, recent data challenges the hypothesis that
locked wards provide improved safety over open-door settings regarding suicide,
absconding and aggression. Furthermore, there is evidence that the introduction
of an open-door policy may lead to short-term reductions in involuntary measures.
The aim of this study was to assess if the introduction of an open-door policy is
associated with a long-term reduction of the frequency of seclusion and forced
medication. METHOD: In this 6-year, hospital-wide, longitudinal, observational
study, we examined the frequency of seclusion and forced medication in 17,359
inpatient cases admitted to the Department of Adult Psychiatry, Universitare
Psychiatrische Kliniken (UPK) Basel, University of Basel, Switzerland. In an
approach to enable a less restrictive policy, six previously closed psychiatric
wards were permanently opened beginning from August 2011. During this process, a
systematic change towards a more patient-centered and recovery-oriented care was
applied. Statistical analysis consisted of generalized estimating equations (GEE)
models. RESULTS: In multivariate analyses controlling for potential confounders,
the implementation of an open-door policy was associated with a continuous
reduction of seclusion (from 8.2 to 3.5%; etap2=0.82; odds ratio: 0.88) and
forced medication (from 2.4 to 1.2%; etap2=0.70; odds ratio: 0.90). CONCLUSION:
This underlines the potential of the introduction of an open-door policy to
attain a long-term reduction in involuntary measures.
PMID- 29331600
TI - A real world study on the genetic, cognitive and psychopathological differences
of obese patients clustered according to eating behaviours.
AB - BACKGROUND: Considering that specific genetic profiles, psychopathological
conditions and neurobiological systems underlie human behaviours, the phenotypic
differentiation of obese patients according to eating behaviours should be
investigated. The aim of this study was to classify obese patients according to
their eating behaviours and to compare these clusters in regard to
psychopathology, personality traits, neurocognitive patterns and genetic
profiles. METHODS: A total of 201 obese outpatients seeking weight reduction
treatment underwent a dietetic visit, psychological and psychiatric assessment
and genotyping for SCL6A2 polymorphisms. Eating behaviours were clustered through
two-step cluster analysis, and these clusters were subsequently compared.
RESULTS: Two groups emerged: cluster 1 contained patients with predominantly
prandial hyperphagia, social eating, an increased frequency of the long allele of
the 5-HTTLPR and low scores in all tests; and cluster 2 included patients with
more emotionally related eating behaviours (emotional eating, grazing, binge
eating, night eating, post-dinner eating, craving for carbohydrates),
dysfunctional personality traits, neurocognitive impairment, affective disorders
and increased frequencies of the short (S) allele and the S/S genotype.
CONCLUSIONS: Aside from binge eating, dysfunctional eating behaviours were useful
symptoms to identify two different phenotypes of obese patients from a
comprehensive set of parameters (genetic, clinical, personality and
neuropsychology) in this sample. Grazing and emotional eating were the most
important predictors for classifying obese patients, followed by binge eating.
This clustering overcomes the idea that 'binging' is the predominant altered
eating behaviour, and could help physicians other than psychiatrists to identify
whether an obese patient has an eating disorder. Finally, recognising different
types of obesity may not only allow a more comprehensive understanding of this
illness, but also make it possible to tailor patient-specific treatment pathways.
PMID- 29331601
TI - Predictors of length of stay in psychiatric inpatient units: Does their effect
vary across countries?
AB - BACKGROUND: Previous studies in individual countries have identified inconsistent
predictors of length of stay (LoS) in psychiatric inpatient units. This may
reflect methodological inconsistencies across studies or true differences of
predictors. In this study we assessed predictors of LoS in five European
countries and explored whether their effect varies across countries. METHODS:
Prospective cohort study. All patients admitted over 14 months to 57 psychiatric
inpatient units in Belgium, Germany, Italy, Poland and United Kingdom were
screened. Putative predictors were collected from medical records and in face-to
face interviews and tested for their association with LoS. RESULTS: Average LoS
varied from 17.9days in Italy to 55.1days in Belgium. In the overall sample being
homeless, receiving benefits, social isolation, diagnosis of psychosis, greater
symptom severity, substance use, history of previous admission and being
involuntarily admitted predicted longer LoS. Several predictors showed
significant interaction effects with countries in predicting LoS. One variable,
homelessness, predicted a different LoS even in opposite directions, whilst for
other predictors the direction of the association was the same, but the strength
of the association with LoS varied across countries. CONCLUSIONS: The same
patient characteristics have a different impact on LoS in different contexts.
Thus, although some predictor variables related to clinical severity and social
dysfunction appear of generalisable relevance, national studies on LoS are
required to understand the complex influence of different patient characteristics
on clinical practice in the given contexts.
PMID- 29331602
TI - A cross-continental analysis of weight gain, psychiatric diagnoses and medication
use during inpatient psychiatric treatment. The international study on physical
illness in mentally ill.
AB - Weight gain among psychiatric inpatients is a widespread phenomenon. This change
in body mass index (BMI) can be caused by several factors. Based on recent
research, we assume the following factors are related to weight gain during
psychiatric inpatient treatment: psychiatric medication, psychiatric diagnosis,
sex, age, weight on admission and geographic region of treatment. 876 of
originally recruited 2328 patients met the criteria for our analysis. Patients
were recruited and examined in mental health care centres in Nigeria (N = 265),
Japan (N = 145) and Western-Europe (Denmark, Germany and Switzerland; N = 466).
There was a significant effect of psychiatric medication, psychiatric diagnoses
and geographic region, but not age and sex, on BMI changes. Geographic region had
a significant effect on BMI change, with Nigerian patients gaining significantly
more weight than Japanese and Western European patients. Moreover, geographic
region influenced the type of psychiatric medication prescribed and the
psychiatric diagnoses. The diagnoses and psychiatric medication prescribed had a
significant effect on BMI change. In conclusion, we consider weight gain as a
multifactorial phenomenon that is influenced by several factors. One can discuss
a number of explanations for our findings, such as different clinical practices
in the geographical regions (prescribing or admission strategies and access-to
care aspects), as well as socio-economic and cultural differences.
PMID- 29331603
TI - Metabolic risk factors in schizophrenia and bipolar disorder: The effect of
comedication with selective serotonin reuptake inhibitors and antipsychotics.
AB - BACKGROUND: The aim of this observational study was to investigate the
relationship between metabolic factors and use of selective serotonin reuptake
inhibitors (SSRIs) combined with olanzapine, quetiapine or risperidone. METHODS:
Data from the Norwegian Thematically Organized Psychosis study, a cross-sectional
study on 1301 patients with schizophrenia (n=868) or bipolar disorder (n=433),
were analyzed. As exposure variables in the linear regression model were included
the dose or serum concentration of SSRIs (n=280) and of olanzapine (n=398),
quetiapine (n=234) or risperidone (n=128). The main outcome variables were levels
of total cholesterol, low and high density lipoprotein (LDL and HDL) cholesterol,
triglycerides and glucose. RESULTS: One defined daily dose (DDD) per day of an
SSRI in addition to olanzapine was associated with an increase in total
cholesterol of 0.16 (CI 0.01 to 0.32) mmol/L (P=0.042) and an increase in LDL
cholesterol of 0.17 (CI 0.02 to 0.31) mmol/L (P=0.022). An SSRI serum
concentration in the middle of the reference interval in addition to quetiapine
was associated with an increase in total cholesterol of 0.39 (CI 0.10 to 0.68)
mmol/L (P=0.011) and an increase in LDL-cholesterol of 0.29 (0.02 to 0.56) mmol/L
(P=0.037). There were no such effects when combined with risperidone.
CONCLUSIONS: The findings indicate only minor deteriorations of metabolic
variables associated with treatment with an SSRI in addition to olanzapine and
quetiapine, and none when combined with risperidone. These results suggest that
SSRIs can be used in combination with antipsychotics, and that the possible
increase in cardiovascular risk is negligible.
PMID- 29331606
TI - Editorial.
PMID- 29331604
TI - Efficacy of intravenous lidocaine on pain relief in patients undergoing
laparoscopic cholecystectomy: A meta-analysis from randomized controlled trials.
AB - OBJECTIVE: Whether intravenous lidocaine has a beneficial role in controlling
acute pain after a laparoscopic cholecystectomy (LC) in currently unknown. We
performed a meta-analysis from randomized controlled trials (RCTs) to determine
the efficacy and safety of intravenous lidocaine for the treatment of acute
postoperative pain after LC. METHODS: In November 2017, a systematic search was
performed in PubMed, EMBASE, Web of Science, ScienceDirect, and the Cochrane
Library. RCTs comparing lidocaine and placebo in patients undergoing LC were
retrieved. The primary endpoint was the visual analogue scale (VAS) score and
opioid requirements at 12 h, 24 h and 48 h. The secondary endpoint was the length
of hospital stay and opioid-related adverse effect. Stata 12.0 was used for the
data analysis. RESULTS: Finally, six RCTs were included in the meta-analysis.
Results indicated that intravenous lidocaine was associated with reduced pain
scores and cumulative opioid consumption at 12 h, 24 h, and 48 h following a LC.
Similarly, lidocaine was associated with a reduction in the incidence of nausea
and vomiting, ileus and pruritus. CONCLUSION: Intravenous use of lidocaine was
able to reduce acute postoperative pain, total opioid requirements and opioid
related adverse effects following a LC. Further studies should determine whether
lidocaine has a positive role in improving the postoperative function after a LC.
PMID- 29331607
TI - Solid dispersions to enhance the delivery of a potential drug candidate LPSF/FZ4
for the treatment of schistosomiasis.
AB - Drug candidate LPSF/FZ4 with promising schistosomicidal properties in vitro was
previously synthesized. However, LPSF/FZ4 has limited aqueous solubility (<1
MUg/mL), leading to ineffective dissolution and, therefore, no meaningful in vivo
comparative studies could be pursued. This study was aimed to develop a proper
amorphous solid dispersion (SD) to enhance the solubility and dissolution rate of
LPSF/FZ4 such that its biological activity could be investigated. To better
understand its physiological behavior, the pKa of LPSF/FZ4, a monoprotic weak
acid with NH group at the imidazolidine ring, was first determined to be 8.13
using an automated SiriusT3. The development of SD systems for LPSF/FZ4 involved
the evaluation of various water-soluble polymer carriers such as PVP K-29/32, PVP
K-90, HPMC K4M, PVPVA 64 and SOLUPLUS(r). The most promising SD systems were
selected through in vitro dissolution studies under nonsink conditions, together
with physicochemical characterization as well as accelerated stability study. It
was shown that SD of 10% LPSF/FZ4 in SOLUPLUS(r) and PVP K-90 could significantly
increase the area-under-the-curve value of the nonsink dissolution profile (AUC
values of the SD in SOLUPLUS(r) and PVP K-90 were 1381.03 and 1342.34 MUL/mL.min,
respectively, and that of the pure crystalline drug was 0.02 MUL/mL.min), a
useful surrogate for the in vivo bioavailability. Cmax values for the SD in
SOLUPLUS(r) (12.50 MUL/mL) and PVP K-90 (25.86 MUL/mL) were also higher than the
one of the crystalline drug (0.02 MUL/mL). The SD system of LPSF/FZ4 in
SOLUPLUS(r) showed a significant increase in schistosomicidal activity in an
animal model as compared with the conventional treatment using crystalline drug,
consistent with the AUC trend from the nonsink dissolution. Thus this SD system
of LPSF/FZ4 could be useful as a potential formulation for treating
schistosomiasis.
PMID- 29331608
TI - Allosteric effects in bacteriophage HK97 procapsids revealed directly from
covariance analysis of cryo EM data.
AB - The information content of cryo EM data sets exceeds that of the electron
scattering potential (cryo EM) density initially derived for structure
determination. Previously we demonstrated the power of data variance analysis for
characterizing regions of cryo EM density that displayed functionally important
variance anomalies associated with maturation cleavage events in Nudaurelia Omega
Capensis Virus and the presence or absence of a maturation protease in
bacteriophage HK97 procapsids. Here we extend the analysis in two ways. First,
instead of imposing icosahedral symmetry on every particle in the data set during
the variance analysis, we only assume that the data set as a whole has
icosahedral symmetry. This change removes artifacts of high variance along
icosahedral symmetry axes, but retains all of the features previously reported in
the HK97 data set. Second we present a covariance analysis that reveals
correlations in structural dynamics (variance) between the interior of the HK97
procapsid with the protease and regions of the exterior (not seen in the absence
of the protease). The latter analysis corresponds well with hydrogen deuterium
exchange studies previously published that reveal the same correlation.
PMID- 29331610
TI - Pseudomonas putida modulates the expression of miRNAs and their target genes in
response to drought and salt stresses in chickpea (Cicer arietinum L.).
AB - MicroRNAs are small non-coding regulatory RNA molecules that play an important
role in the modulation of gene expression during various environmental stresses.
Pseudomonas putida RA, a plant growth promoting rhizobacteria (PGPR) colonizes
the root surface of plants improving their growth and development during abiotic
stresses modulating the expression of stress-responsive genes; however, the
impact of RA on stress responsive-miRNA remains elusive. The present study was an
attempt to delineate the role of PGPR in modulating stress responsive-miRNAs in a
tolerant desi chickpea genotype exposed to drought and salt stresses. The
existence of variable expression patterns of individual miRNAs and their target
genes under these stresses at different time points indicate a distinct miRNA
mediated perception and response mechanisms operating under these stresses in the
presence or absence of RA in chickpea.
PMID- 29331609
TI - Structure of the Bacillus anthracis dTDP-l-rhamnose biosynthetic pathway enzyme:
dTDP-alpha-d-glucose 4,6-dehydratase, RfbB.
AB - Many bacteria require l-rhamnose as a key cell wall component. This sugar is
transferred to the cell wall using an activated donor dTDP-l-rhamnose, which is
produced by the dTDP-l-rhamnose biosynthetic pathway. We determined the crystal
structure of the second enzyme of this pathway dTDP-alpha-d-glucose 4,6
dehydratase (RfbB) from Bacillus anthracis. Interestingly, RfbB only crystallized
in the presence of the third enzyme of the pathway RfbC; however, RfbC was not
present in the crystal. Our work represents the first complete structural
characterization of the four proteins of this pathway in a single Gram-positive
bacterium.
PMID- 29331611
TI - Resistance to peer influence moderates the relationship between perceived (but
not actual) peer norms and binge drinking in a college student social network.
AB - INTRODUCTION: Adolescent and young adult binge drinking is strongly associated
with perceived social norms and the drinking behavior that occurs within peer
networks. The extent to which an individual is influenced by the behavior of
others may depend upon that individual's resistance to peer influence (RPI).
METHODS: Students in their first semester of college (N=1323; 54.7% female, 57%
White, 15.1% Hispanic) reported on their own binge drinking, and the perceived
binge drinking of up to 10 important peers in the first-year class. Using network
autocorrelation models, we investigated cross-sectional relationships between
participant's binge drinking frequency and the perceived and actual binge
drinking frequency of important peers. We then tested the moderating role of RPI,
expecting that greater RPI would weaken the relationship between perceived and
actual peer binge drinking on participant binge drinking. RESULTS: Perceived and
actual peer binge drinking were statistically significant predictors of
participant binge drinking frequency in the past month, after controlling for
covariates. RPI significantly moderated the association between perceptions of
peer binge drinking and participant's own binge drinking; this association was
weaker among participants with higher RPI compared to those with lower RPI. RPI
did not interact with the actual binge drinking behavior of network peers.
CONCLUSIONS: RPI may function to protect individuals from the effect of their
perceptions about the binge drinking of peers, but not from the effect of the
actual binge drinking of peers.
PMID- 29331612
TI - Arterial Spin Labeling Cerebral Perfusion Magnetic Resonance Imaging in Migraine
Aura: An Observational Study.
AB - BACKGROUND: Changes in cerebral perfusion during migraine with aura (MA) have
been assessed mainly using dynamic susceptibility contrast (DSC) magnetic
resonance perfusion imaging. A contrast agent-free method to assess these changes
would be desirable. We assessed changes in cerebral perfusion during MA using
arterial spin labeling (ASL) perfusion magnetic resonance imaging. METHODS: We
investigated 4 patients with a standardized protocol including ASL perfusion
imaging during MA (n = 2) or early headache phase (n = 2) and asymptomatic follow
up. Semiquantitative evaluation was done using a region of interest (ROI) within
hypoperfused or hyperperfused areas and corresponding ROIs in the contralateral
hemisphere. Relative ratios of mean perfusion in the corresponding ROIs were
calculated. DSC imaging was done at initial time points and compared visually
with ASL findings. RESULTS: In all patients, regional perfusion changes were
detected in the acute phase. These abnormalities did not respect the boundaries
of major cerebral vascular territories but overlapped onto adjoining regions.
During MA, adjacent hypoperfused and hyperperfused areas were found, whereas
during headache, regional hyperperfusion only was observed. Perfusion
abnormalities normalized on follow-up. CONCLUSIONS: ASL perfusion imaging is a
contrast agent-free method suitable for assessment of reversible perfusion
changes during or immediately after MA.
PMID- 29331613
TI - Internal Carotid Artery Web as the Cause of Recurrent Cryptogenic Ischemic
Stroke.
AB - Carotid artery web is considered an exceptional cause of recurrent ischemic
strokes in the affected arterial territory. The underlying pathology proposed for
this entity is an atypical fibromuscular dysplasia. We present the case of a 43
year-old woman with no cardiovascular risk factors who had experienced 2
cryptogenic ischemic strokes in the same arterial territory within an 11-month
period. Although all diagnostic tests initially yielded normal results, detailed
analysis of the computed tomography angiography images revealed a carotid web;
catheter angiography subsequently confirmed the diagnosis. Carotid surgery was
performed, since which time the patient has remained completely asymptomatic. The
histological finding of intimal hyperplasia is consistent with previously
reported cases of carotid artery web. Carotid artery web is an infrequent cause
of stroke, and this diagnosis requires a high level of suspicion plus a detailed
analysis of vascular imaging studies.
PMID- 29331614
TI - The Burden of Stroke Mimics: Present and Future Projections.
AB - BACKGROUND AND PURPOSE: An increasing proportion of patients presenting with
suspected stroke prove to have other conditions, often referred to as stroke
mimics. The aim of this study was to present a projection of the number of
hospitalized strokes, transient ischemic attacks (TIAs), and stroke mimics in
Norway up to the year 2050 based on expected demographic changes, to estimate the
burden of stroke mimics in the coming decades. MATERIALS AND METHODS: This
prospective study included all admissions to the stroke unit of Akershus
University Hospital from March 1, 2012, to February 28, 2013. Relevant resource
use was recorded. Based on the age- and sex-specific absolute incidences for the
study period, the expected numbers of strokes, TIAs, and stroke mimics in the
entire Norwegian population were computed for every fifth year for the period
2020-2050. RESULTS: We included 1881 admissions, of which 38.2% were stroke
mimics. With constant age- and sex-dependent incidence rates, we estimated that
the number of strokes and stroke mimics will respectively increase by 121.3% and
88.7% (men) and 97.6% and 71.7% (women). For hospital admission levels to stay
constant at the 2013 level, an annual reduction of 2.1% and 1.7% (men) and 1.8%
and 1.5% (women) must take place for strokes and mimics, respectively.
CONCLUSIONS: A significant proportion of stroke unit admissions prove to have
other conditions than stroke. With constant age- and sex-dependent incidence
rates, the number of stroke mimics admissions will increase substantially over
the next decades.
PMID- 29331615
TI - Increased brain glucocorticoid actions following social defeat in rats
facilitates the long-term establishment of social subordination.
AB - Social rank is frequently established through aggressive encounters between new
conspecifics. Despite increasing evidence suggesting that social rank is critical
for the well-being of both humans and animals, knowledge about the factors
influencing social rank remain scarce. Stress was previously shown to affect the
establishment and maintenance of social hierarchies in rats. Likewise, increasing
systemic corticosterone levels post-encounter in the emerging subordinate rat
facilitates the long-term establishment of social subordination. Here, we
investigated whether central corticosterone actions are sufficient to mediate
this effect. Our data shows that, indeed, an intracerebroventricular
corticosterone injection given to the emerging subordinate rat facilitates the
long-term maintenance of the subordinate rank. Next, we attempted to identify a
particular brain region in which enhancement of corticosterone actions could be
sufficient to exert the facilitation of a long-term maintenance in the emerging
subordinate brain. However, post-encounter administration of corticosterone into
the basolateral amygdala, medial amygdala, lateral septum and the nucleus
accumbens, brain regions selected for their implication in social rank
establishment and emotional modulation of memory, did not affect long-term social
subordination. Our study highlights the involvement of intracerebral
corticosterone actions on the facilitation of long-lasting subordinate behavior,
likely by having a modulatory role in the neurobehavioral plasticity engaged in
the shaping of social subordination.
PMID- 29331616
TI - Paediatric video laryngoscopy and airway management: What's the clinical
evidence?
AB - The major complications of paediatric airway management are uncommon, but the
outcomes are often severe. Over the last decade, additions and advancements in
the devices and technology have significantly improved our ability to manage
difficult paediatric airways safely. Videolaryngoscopy involves the use of video
and optical technology to facilitate indirect visualisation of the larynx during
intubation and has been seen as an evolutionary step in intubation technology.
Over the past few years, videolaryngoscopes have been receiving plenty of
attention as new airway devices for use in paediatric patients. The objective of
this narrative review is to specify the existing clinical evidence regarding the
efficiency and safety of videolaryngoscopy in paediatric airway management.
PMID- 29331617
TI - Asthma predictive index in relation to respiratory mechanics by impulse
oscillometry in recurrent wheezers.
AB - BACKGROUND: The identification of children who will have persistent asthma has
become a focus of recent research. The aim of this study was to assess whether
impulse oscillometry (IOS) has a diagnostic value to predict modified API (asthma
predictive index) in pre-schoolers with recurrent wheezing. METHODS: Pre-school
children aged 3-6 years with recurrent wheezing were enrolled. The study
population was divided into two groups based on mAPI criteria. Lung function was
assessed by IOS. RESULTS: 115 children were assessed; 75 (65.2%) of them were
male. The median age was 39 months (min: 36, max: 68 months). 64 (55.6%) of the
children were mAPI positive. The R5-R20% levels of children with positive mAPI
were significantly higher compared to negative mAPI. Also, R5-R20% levels of
children with parental asthma and R20% pred and resonant frequency (Fres) levels
of children with inhalant sensitization were higher than those without. No
significant differences were found in IOS indices between groups based on the
presence of atopic dermatitis, food sensitization, eosinophilia, inhaled
corticosteroid usage or wheezing without colds. R5-R20% and total IgE values were
found to be significantly related to positive mAPI (aOR: 1.40, p=0.022 and aOR:
1.02, p=0.001, respectively). In the ROC analysis, R5-R20% levels >14.4 had a
sensitivity of 75% and specificity of 53% for predicting a positive mAPI
(p=0.003). CONCLUSION: IOS may help clinicians to identify the pre-school
wheezers with a high risk of asthma.
PMID- 29331618
TI - Efficacy and safety of sublingual immunotherapy with Dermatophagoides farinae
drops in pre-school and school-age children with allergic rhinitis.
AB - BACKGROUND: The safety and efficacy of sublingual immunotherapy (SLIT) have been
confirmed by many studies. However, in China, the research on efficacy and safety
in young and older children with allergic rhinitis (AR) is still rare. OBJECTIVE:
The aim of this retrospective study is to evaluate the efficacy and safety of
SLIT with Dermatophagoides farinae drops in pre-school and school-age children
with AR. METHODS: A total of 282 subjects aged 2-13 years with AR received a two
year course of sublingual immunotherapy along with pharmacotherapy. According to
the age, patients were defined as the pre-school group (2-6 years old, n=116) and
school-age group (7-13 years old, n=166). Total nasal rhinitis symptom scores
(TNSS), visual analogue score (VAS) and total medication scores (TMS) were
evaluated at four time points: baseline, after SLIT for half a year, one year and
two years. The adverse events (AEs) were evaluated at each visit. RESULTS: After
two-year SLIT, the four rhinitis symptom scores, TNSS, VAS and TMS scores were
significantly lower than baseline (all P<0.05). The comparison of efficacy
between one and two-year duration showed no significant difference in global
clinical outcomes (all P>0.05). In addition, there were no significant
differences between the pre-school and school-age group in TNSS (all P>0.05), VAS
(all P>0.05) and TMS scores (P>0.05) after SLIT for half a year, one year and two
years. No severe systemic AEs were reported. CONCLUSION: SLIT with D. farinae
drops is clinically effective and safe in pre-school and school-age patients with
house dust mites (HDMs)-induced AR.
PMID- 29331619
TI - Mycoplasma pneumoniae and toll-like receptors: A mutual avenue.
AB - Mycoplasma pneumoniae is an intracellular bacterium leading to several
complications in humans. M. pneumoniae is cleared in some cases and induces
complications in others. The main responsible mechanisms regarding the
controversy are yet to be cleared. Toll-like receptors (TLRs) are the important
cell membrane and intracellular receptors which recognize a wide range of
microbial macromolecules. The roles of TLRs in the eradication of several
pathogens and also induction of their related complications have been
demonstrated. This review article presents recent data about the roles of TLRs in
the induction of immune responses which lead to M. pneumoniae eradication and
related complications.
PMID- 29331620
TI - Antagonistic effect of nano-ZnO and cetyltrimethyl ammonium chloride on the
growth of Chlorella vulgaris: Dissolution and accumulation of nano-ZnO.
AB - The interaction of nanoparticles with coexisting chemicals affects the fate and
transport of nanoparticles, as well as their combined effects on aquatic
organisms. Here, we evaluated the joint effect of ZnO nanoparticle (nano-ZnO) and
cetyltrimethyl ammonium chloride (CTAC) on the growth of Chlorella vulgaris and
explored the possible mechanism. Results showed that an antagonistic effect of
nano-ZnO and CTAC (0.1, 0.2 and 0.3 mg L-1) was found because CTAC stop nano-ZnO
being broken down into solution zinc ions (Zn2+). In the presence of CTAC, the
zinc (including nano-ZnO and released Zn2+) showed a higher adsorption on bound
extracellular polymeric substances (B-EPS) but lower accumulation in the algal
cells. Moreover, we directly demonstrated that nano-ZnO was adsorbed on the algal
B-EPS and entered into the algal cells by transmission electron microscope
coupled with energy dispersive X-ray (TEM-EDX). Hence, these results suggested
that the combined system of nano-ZnO and CTAC exhibited an antagonistic effect
due to the inhibition of CTAC on dissolution of nano-ZnO and accumulation of the
zinc in the algal cells.
PMID- 29331621
TI - Silver ion-enhanced particle-specific cytotoxicity of silver nanoparticles and
effect on the production of extracellular secretions of Phanerochaete
chrysosporium.
AB - This study investigated the influence of silver ions (Ag+) on the cytotoxicity of
silver nanoparticles (AgNPs) in Phanerochaete chrysosporium and noted the degree
of extracellular secretions in response to the toxicant's stress. Oxalate
production was elicited with moderate concentrations of 2,4-dichlorophenol (2,4
DCP) and AgNPs reaching a plateau at 10 mg/L and 10 MUM, respectively. Increased
oxalate accumulation was accompanied by higher activities of manganese peroxidase
(MnP) and lignin peroxidase (LiP). However, the secretion of oxalate, MnP and LiP
was significantly inhibited owing to Ag+ incorporation into AgNP solution.
Production of extracellular polymeric substances (EPS) significantly elevated
with an increase in 2,4-DCP concentrations; however, after 24 h of exposure to
100 mg/L 2,4-DCP, an obvious decrease in EPS occurred, indicating that part of
EPS could be consumed as carbon and energy sources to ameliorate biological
tolerance to toxic stress. Furthermore, AgNP-induced "particle-specific"
cytotoxicity was substantially enhanced with additional Ag+ as evidenced by its
significant negative impact on cellular growth, plasma membrane integrity, and
morphological preservation compared with AgNPs at equal Ag concentration.
PMID- 29331622
TI - Value of Serial Multiparametric Magnetic Resonance Imaging and Magnetic Resonance
Imaging-guided Biopsies in Men with Low-risk Prostate Cancer on Active
Surveillance After 1 Yr Follow-up.
AB - BACKGROUND: Active surveillance (AS) aims to reduce overtreatment of low-risk
prostate cancer (PC). Incorporating multiparametric magnetic resonance imaging
(mp-MRI) and MR-guided biopsy (MRGB) in an AS protocol might contribute to more
accurate identification of AS candidates. OBJECTIVE: To evaluate the value of 3T
mp-MRI and MRGB in PC patients on AS at inclusion and after 12-mo follow-up.
DESIGN, SETTING, AND PARTICIPANTS: Patients with cT1c-cT2 PC, prostate-specific
antigen (PSA) <=10ng/ml, PSA density <0.2ng/ml/ml, and Gleason scores (GSs) of
<=6 and <=2 positive biopsy cores were included and followed in an AS protocol
including mp-MRI and MRGB. The mp-MRI and MRGB were performed at <3 and 12 mo
after diagnosis. Reclassification was defined as GS >6, >2 positive cores at
repeat transrectal ultrasound-guided biopsy (TRUSGB), presence of PC in >3
separate cancer foci upon both MRGB and TRUSGB, or cT3 tumor on mp-MRI. OUTCOME
MEASUREMENTS AND STATISTICAL ANALYSIS: Reclassification rates, treatment after
discontinuation, and outcome on radical prostatectomy after discontinuing AS were
reported. Uni- and multivariate analyses were performed to identify predictors of
reclassification after 1 yr. RESULTS AND LIMITATIONS: From 2009 to 2013, a total
of 111 of 158 patients were consecutively and prospectively included. Around
initial diagnosis, 36 patients were excluded from the study protocol; mp-MRI+MRGB
reclassified 25/111 (23%) patients, and 11 patients were excluded at own request.
Reasons for reclassification were as follows: GS upgrade (15/25, 60%); cT3
disease (3/25, 12%); suspicion of bone metastases (1/25, 4%); and multifocal
disease upon MRGB (6/25, 24%). Repeat examinations after 1 yr showed
reclassification in 33/75 patients (44%). Reasons were the following: GS upgrade
upon TRUSGB (9/33, 27%); volume progression upon TRUSGB (9/33, 27%); cT3 disease
upon mp-MRI (1/33, 3%); GS upgrade upon MRGB (1/33, 3%); volume progression upon
MRGB (1/33, 3%); multifocal disease upon MRGB (2/33, 6%); and upgrade or upstage
upon both TRUSGB and MRGB (10/33, 30%). On logistic regression analysis, the
presence of cancer at initial mp-MRI and MRGB examinations was the only predictor
of reclassification after 1 yr (odds ratio 5.9, 95% confidence interval 2.0
17.6). CONCLUSIONS: Although mp-MRI and MRGB are of additional value in the
evaluation of PC patients on AS, the value of mp-MRI after 1 yr was limited. As a
considerable percentage of GS >=7 PC after 1 yr was detected only by TRUSGB,
TRUSGB cannot be omitted yet. PATIENT SUMMARY: More aggressive tumors are
detected if low-risk prostate cancer patients are additionally monitored by
magnetic resonance imaging. However, some high-grade tumors are detected only by
transrectal ultrasound-guided biopsy.
PMID- 29331623
TI - Male Sexual Dysfunction and Hypogonadism Guidelines for the Aging Male.
AB - Cognitive and somatiform changes occur with ageing and are often attributed to
late-onset hypogonadism. Testosterone replacement in older men remains
controversial despite increasing evidence of symptomatic and clinical benefit in
relation to improvements in sexual dysfunction, muscle mass, and diabetic
control. The controversial areas related to cardiovascular safety and risk of
prostate cancer need to be considered.
PMID- 29331624
TI - Comprehensive Geriatric Assessment in the Older Adult with Cancer: A Review.
AB - CONTEXT: The number of older adults with cancer is expected to increase rapidly
in the upcoming decades. Aging is heterogeneous and chronological age is often
not reflective of biological age. A comprehensive geriatric assessment (CGA) is
an in-depth assessment of multiple domains of health that results in better
assessment of a patient's overall health and fitness and allows directed
intervention to improve patient outcomes. OBJECTIVE: To review the value of CGA
for older adults with cancer, CGA composition and tools that can be utilized, and
the feasibility of including CGA in oncologic practice. EVIDENCE ACQUISITION: The
currently available evidence on CGA for older adults with cancer was reviewed.
EVIDENCE SYNTHESIS: A CGA can highlight unidentified health problems and identify
patients at higher risk of mortality, functional decline, surgical complications,
chemotherapy intolerance, and chemotherapy toxicity. It has been shown that CGA
is feasible in the oncology clinic, but geriatric screening tools may be useful
to specifically identify patients who would benefit from a full CGA. CONCLUSIONS:
CGA is feasible and can identify patients at higher risk of adverse events such
as mortality, functional decline, surgical complications, and chemotherapy
toxicity. Clinicians should consider incorporating CGA when assessing and caring
for older adults with cancer. PATIENT SUMMARY: In this report, we review the
benefits of a comprehensive geriatric assessment (CGA), a detailed in-depth
assessment that identifies health problems not typically identified during
routine assessments, for older adults with cancer. We describe the different
domains of the CGA and suggest tools to utilize, as well as ways to incorporate
CGA into the cancer care setting.
PMID- 29331625
TI - Proposing priorities of intervention for the recovery of native fish populations
using hierarchical ranking of environmental and exotic species impact.
AB - The freshwater populations of native fish species (Ns) have reached critical
levels in many parts of the world due to combined habitat deterioration by human
interventions and exotic fish species (Es) invasions. These alarming conditions
require combined and well-designed interventions for restoring environmental
quality and restricting Es invasion. The aim of the study is to propose a method
to design spatially explicit priorities of intervention for the recovery of Ns
populations in highly impacted freshwater systems by exotic multi-species
invasion and water quality (WQ) degradation. WQ and Es are used as Ns
descriptors, which require intervention. The method uses gradient analysis
(ordination method of Canonical Correspondence Analysis) for assessing the
weights of Ns descriptors' effects, which are further used to develop weighted
severity indices; the severity index of WQ (Swq) and Es invasion (Se),
respectively. Swq and Se are further merged to one combined total severity index
St. The proposed method provides a) a ranking of the sites, based on the values
of St, which denotes the priority for combined intervention in space and can be
visualized in maps, b) a ranking of the most important Ns descriptors for each
site to perform site-specific interventions, and c) Es rankings based on their
potential threat on Ns for species-specific interventions. WQ, Es and Ns data
from 208 sampling sites located in the Emilia-Romagna Region (Northern Italy)
were used as a case study for the presentation of the proposed method. The
application of the method showed that the north and northwestern lowland areas of
Emilia-Romagna region presented the higher priority for intervention since the Ns
of these areas are the most impacted from combined Es invasions and WQ
degradation. Specific Es belonging to cyprinids, which are mostly responsible for
the decline of aquatic vegetation and the increase of water turbidity, and a top
Es predator (Wels catfish) were mostly present in these areas. Additionally, the
most important WQ stressors of Ns were found to be COD, BOD and temperature that
are all connected to oxygen depletion. The aforementioned conditions in the areas
described by high priority for intervention can be used as a basis for the
development of specific Ns conservation practices targeting the containment of
the most harmful Es, the restoration of aquatic vegetation and the improvement of
oxygen conditions.
PMID- 29331626
TI - Implicit individual discount rate in China: A contingent valuation study.
AB - Two contingent valuation (CV) surveys were conducted in Kunming, China, to
estimate households' willingness to pay (WTP) for the Panlong River
rehabilitation project. The two surveys were conducted using the same procedures
and questionnaires except for the payment schedule arrangements, which permitted
a calculation of respondents' implicit discount rate. The surveys provided two
estimates of WTP, one with a mean of 23 Yuan in monthly payment over 5 years and
the other with a mean of 311 Yuan in a lump-sum payment that will cover all the
expenses for a period of 5 years. The results produce an estimate of monthly
discount rate of 7.6%-12.6% or annual discount rate of 141-315%. The estimates
are higher than that reported from those studies conducted in the U.S., but are
compatible with that of some other studies. This study also shows that both mean
individual WTP and implicit individual discount rates are closely related to
household demographic and economic characteristics and environment-related
perceptions, as reported in the studies conducted in other countries.
PMID- 29331627
TI - Use of interactive data visualization in multi-objective forest planning.
AB - Common to multi-objective forest planning situations is that they all require
comparisons, searches and evaluation among decision alternatives. Through these
actions, the decision maker can learn from the information presented and thus
make well-justified decisions. Interactive data visualization is an evolving
approach that supports learning and decision making in multidimensional decision
problems and planning processes. Data visualization contributes the formation of
mental image data and this process is further boosted by allowing interaction
with the data. In this study, we introduce a multi-objective forest planning
decision problem framework and the corresponding characteristics of data. We
utilize the framework with example planning data to illustrate and evaluate the
potential of 14 interactive data visualization techniques to support multi
objective forest planning decisions. Furthermore, broader utilization
possibilities of these techniques to incorporate the provisioning of ecosystem
services into forest management and planning are discussed.
PMID- 29331628
TI - Getting into the Swing of things: An investigation into rhythmic unimanual
coordination in typically developing children.
AB - Unimanual coordination is a vital component of everyday life and underpins
successful engagement of many activities of daily living and physical activity
participation. The ability to coordinate with environmental stimuli has been
extensively studied in adults in a variety of situations. However, we know little
about these processes in children and even less about how these processes change
as age increases. This paper examines children's performance in a rhythmic
unimanual coordination task using a handheld pendulum. Participants (aged 6, 9
and 11 years) manipulated the pendulum at 3 frequencies (preferred frequency,
+20% of preferred and -20% of preferred frequency) in coordination with 3 stimuli
(Visual, Auditory and Visual-Auditory combined). Results showed that children's
coordination levels and movement variability improved with age, however still
fell below those observed in adults. In addition children demonstrated
preferences for visual stimuli or multisensory stimuli compared to auditory
stimuli on their own Interestingly, children were found to demonstrate different
movement amplitudes for -20%, preferred and +20% frequency conditions. In
conclusion, children's unimanual coordination levels were found to follow the
typical maturation process and improve with age. Further to this, findings
suggest the potential benefit of multisensory information for uni manual
coordination in children.
PMID- 29331629
TI - Growth and maturity: A quantitative systematic review and network analysis in
anthropometric history.
AB - This paper reviews the current wealth of anthropometric history since the early
efforts of Robert Fogel in the 1970s. The survey is based on a quantitative
systematic review of the literature and counts a total of 447 peer-reviewed
articles being published in the main leading journals in economic history,
economics and biology. Data are analysed using network analysis by journal and
author and the main contributions of anthropometric history are highlighted,
pointing to future areas of inquiry. The contributions of books and book chapters
are also quantified and analysed.
PMID- 29331630
TI - mRNA function after intracellular delivery and release.
AB - Nanocarrier-mediated mRNA delivery and release into the cells with subsequent
translation to protein is of interest in the context of the development of a new
generation of drugs. In particular, this protein can play a role of a
transcription factor and be used as a tool to regulate temporarily the genetic
networks. The corresponding transient kinetics of gene expression are expected to
depend on the mechanism and duration of mRNA release. Assuming the release to be
rapid on the time scale of other steps, the author shows theoretically the mRNA
related transient features of gene expression occurring in stable, bistable, and
oscillatory regimes in a single cell. Qualitatively, the results obtained are
found to be fairly similar to those reported earlier for the situation when the
release is slow. Thus, the features of the transient kinetics under consideration
appear to be less sensitive to the duration of mRNA release compared to what one
might expect.
PMID- 29331632
TI - CT scanning to diagnose CAA: back to the future?
PMID- 29331631
TI - The Edinburgh CT and genetic diagnostic criteria for lobar intracerebral
haemorrhage associated with cerebral amyloid angiopathy: model development and
diagnostic test accuracy study.
AB - BACKGROUND: Identification of lobar spontaneous intracerebral haemorrhage
associated with cerebral amyloid angiopathy (CAA) is important because it is
associated with a higher risk of recurrent intracerebral haemorrhage than
arteriolosclerosis-associated intracerebral haemorrhage. We aimed to develop a
prediction model for the identification of CAA-associated lobar intracerebral
haemorrhage using CT features and genotype. METHODS: We identified adults with
first-ever intracerebral haemorrhage diagnosed by CT, who died and underwent
research autopsy as part of the Lothian IntraCerebral Haemorrhage, Pathology,
Imaging and Neurological Outcome (LINCHPIN) study, a prospective, population
based, inception cohort. We determined APOE genotype and radiologists rated CT
imaging appearances. Radiologists were not aware of clinical, genetic, and
histopathological features. A neuropathologist rated brain tissue for small
vessel diseases, including CAA, and was masked to clinical, radiographic, and
genetic features. We used CT and APOE genotype data in a logistic regression
model, which we internally validated using bootstrapping, to predict the risk of
CAA-associated lobar intracerebral haemorrhage, derive diagnostic criteria, and
estimate diagnostic accuracy. FINDINGS: Among 110 adults (median age 83 years
[IQR 76-87], 49 [45%] men) included in the LINCHPIN study between June 1, 2010
and Feb 10, 2016, intracerebral haemorrhage was lobar in 62 (56%) participants,
deep in 41 (37%), and infratentorial in seven (6%). Of the 62 participants with
lobar intracerebral haemorrhage, 36 (58%) were associated with moderate or severe
CAA compared with 26 (42%) that were associated with absent or mild CAA, and were
independently associated with subarachnoid haemorrhage (32 [89%] of 36 vs 11
[42%] of 26; p=0.014), intracerebral haemorrhage with finger-like projections (14
[39%] of 36 vs 0; p=0.043), and APOE E4 possession (18 [50%] of 36 vs 2 [8%] of
26; p=0.0020). A prediction model for CAA-associated lobar intracerebral
haemorrhage using these three variables had excellent discrimination (c statistic
0.92, 95% CI 0.86-0.98), confirmed by internal validation. For the rule-out
criteria, neither subarachnoid haemorrhage nor APOE E4 possession had 100%
sensitivity (95% CI 88-100). For the rule-in criteria, subarachnoid haemorrhage
and either APOE E4 possession or finger-like projections had 96% specificity (95%
CI 78-100). INTERPRETATION: The CT and APOE genotype prediction model for CAA
associated lobar intracerebral haemorrhage shows excellent discrimination in this
cohort, but requires external validation. The Edinburgh rule-in and rule-out
diagnostic criteria might inform prognostic and therapeutic decisions that depend
on identification of CAA-associated lobar intracerebral haemorrhage. FUNDING: UK
Medical Research Council, The Stroke Association, and The Wellcome Trust.
PMID- 29331633
TI - Organ donation in the ICU: A document analysis of institutional policies,
protocols, and order sets.
AB - OBJECTIVE: To better understand how local policies influence organ donation
rates. RESEARCH METHODOLOGY/DESIGN: We conducted a document analysis of our ICU
organ donation policies, protocols and order sets. We used a systematic search of
our institution's policy library to identify documents related to organ donation.
We used Mindnode software to create a publication timeline, basic statistics to
describe document characteristics, and qualitative content analysis to extract
document themes. SETTING: Documents were retrieved from Hamilton Health Sciences,
an academic hospital system with a high volume of organ donation, from database
inception to October 2015. FINDINGS: We retrieved 12 active organ donation
documents, including six protocols, two policies, two order sets, and two
unclassified documents, a majority (75%) after the introduction of donation after
circulatory death in 2006. Four major themes emerged: organ donation process,
quality of care, patient and family-centred care, and the role of the
institution. These themes indicate areas where documented institutional standards
may be beneficial. CONCLUSION: Further research is necessary to determine the
relationship of local policies, protocols, and order sets to actual organ
donation practices, and to identify barriers and facilitators to improving
donation rates.
PMID- 29331634
TI - Of blood and bone: the sotatercept adventure.
PMID- 29331636
TI - Cell wall damage and oxidative stress in Candida albicans ATCC10231 and
Aspergillus niger caused by palladium nanoparticles.
AB - In this work the toxic effect of Palladium nanoparticles (PdNPs) was investigated
in two eukaryotic cell models, Candida albicans and Aspergillus niger. PdNPs were
synthesized by chemical reduction method, obtaining spherical NPs with a primary
size ranging from 3 to 15 nm. PdNPs showed a hydrodynamic size of 1548 nm in
Lee's minimum media. Minimal inhibitory concentration was determined at 200 and
250 ppm for Candida albicans and Aspergillus niger respectively, revealing a
significant cell growth inhibition (ANOVA and tukey analysis, alpha = 0.5).
Reactive Oxygen Species levels were increased in both microorganisms. Confocal,
scanning and transmission electron microscopy studies revealed cell wall damage
and cellular morphology changes, induced by the interaction of PdNPs, in both
microorganisms.
PMID- 29331635
TI - Sotatercept with long-term extension for the treatment of anaemia in patients
with lower-risk myelodysplastic syndromes: a phase 2, dose-ranging trial.
AB - BACKGROUND: Myelodysplastic syndromes are characterised by ineffective
erythropoiesis leading to anaemia. Sotatercept (ACE-011) is a novel activin
receptor type IIA fusion protein that acts as a ligand trap to neutralise
negative regulators of late-stage erythropoiesis. The aim of the study was to
establish a safe and effective dose of sotatercept for the treatment of anaemia
in patients with lower-risk myelodysplastic syndromes. METHODS: This open-label,
multicentre, dose-ranging, phase 2 trial took place at 11 treatment centres in
the USA and France. Eligible patients were aged 18 years or older, had
International Prognostic Scoring System-defined low-risk or intermediate-1-risk
myelodysplastic syndromes, had anaemia requiring red blood cell (RBC)
transfusions, and were ineligible for, or refractory to, erythropoiesis
stimulating agents (ESAs). Patients were not eligible if they had chromosome 5q
deletion myelodysplastic syndromes without documented failure of lenalidomide.
Patients were randomly assigned to receive either 0.1 or 0.3 mg/kg sotatercept
subcutaneously, using a permuted-block method with stratification for serum
erythropoietin concentration and transfusion burden. Patients were assigned to
0.5, 1.0, and 2.0 mg/kg groups in a non-randomised fashion. The primary efficacy
endpoint was the proportion of patients who achieved haematological improvement
erythroid (HI-E), according to International Working Group 2006 criteria.
Efficacy and safety analyses were done in the intention-to-treat population. This
trial is registered at ClinicalTrials.gov, number NCT01736683 and at EU Clinical
Trials Register, number 2012-002601-22, and is ongoing. FINDINGS: Between Dec 5,
2012, and July 22, 2015, 74 patients were enrolled into the study (seven to
receive 0.1 mg/kg sotatercept, six to 0.3 mg/kg, 21 to 0.5 mg/kg, 35 to 1.0
mg/kg, and five to 2.0 mg/kg). 36 (49%; 95% CI 38-60) of 74 patients achieved HI
E; 29 (47%; 95% CI 35-59) of 62 patients with a high transfusion burden achieved
HI-E (RBC-transfusion reduction from baseline of 4 or more units for at least 56
days), and seven (58%; 95% CI 32-81) of 12 patients with a low transfusion burden
achieved HI-E (haemoglobin increase of 1.5 g/dL or more sustained for at least 56
days in the absence of transfusions). The most commonly reported adverse events
were fatigue in 19 (26%) of 74 patients and peripheral oedema in 18 (24%) of 74
patients. Grade 3-4 treatment-emergent adverse events (TEAEs) were reported in 25
(34%) of 74 patients; four (5%) patients had grade 3-4 TEAEs that were considered
to be treatment related. The most common grade 3-4 TEAEs were lipase increase and
anaemia, which each occurred in three (4%) of 74 patients. 17 (23%) of 74
patients had at least one serious TEAE, and one patient died from a treatment
emergent subdural haematoma due to a fall. INTERPRETATION: Sotatercept, a novel
activin-receptor fusion protein, was well tolerated and effective for the
treatment of anaemia in patients with lower-risk myelodysplastic syndromes in
whom previous ESA treatment had failed. Treatment with sotatercept could be
beneficial for these patients who have few available treatment options. FUNDING:
Celgene Corporation.
PMID- 29331637
TI - Development of a multi-dimensional scale to measure trauma associated with child
sexual abuse (MSCSA) and its ramifying impacts on children: A pilot study.
AB - BACKGROUND: With the rising incidence of CSA in India and absence of culturally
competent tool to assess the impact of trauma, there is a dire need for
development of a comprehensive scale to assess the impact of trauma on children.
Thus, the present study aims to develop a multi-dimensional CSA tool for children
aged between 7 and 13 years. METHOD: Qualitative research method of FGD/Key
Interviews with 4 group participants (Parents, counsellors, mental health and
medical professionals) and in-depth interview with children having history of CSA
was conducted along with item pooling from existing scales. Scale domain and sub
constructs were identified through thematic analysis of the qualitative data and
statements extracted through item pooling. Face and content validity was obtained
followed by the administration of the scale on pilot sample of 30 children
meeting selection criteria of the study. RESULTS: 6 domains of the multi
dimensional impact of trauma was identified (i.e. Behavioral, Emotional,
Cognition, Biological, Psychopathology and Social Functioning) which was
constructed in the form of 85 scale statements across 6 domains and 48 sub
constructs on a 3-point Likert scale of response in both Hindi as well as English
language. The scale was found to be having high reliability and average inter
item and inter-domain correlation. Modification of scale items based on pilot
study findings and expert feedback analysis done to obtain a final scale
containing 78 items. DISCUSSION: Discussion done primarily in terms of scale's
psychometric properties, its clinical & research implications, especially
focusing on cultural competency of the scale.
PMID- 29331638
TI - Comparative analysis of membrane protein structure databases.
AB - BACKGROUND: Membrane proteins play important roles in cell survival and cell
communication, as they function as transporters, receptors, anchors and enzymes.
They are also potential targets for drugs that block receptors or inhibit enzymes
related to diseases. Although the number of known structures of membrane proteins
is still small relative to the size of the proteome as a whole, many new membrane
protein structures have been determined recently. SCOPE OF THE ARTICLE: We
compared and analyzed the widely used membrane protein databases, mpstruc,
Orientations of Proteins in Membranes (OPM), and PDBTM, as well as the extended
dataset of mpstruc based on sequence similarity, the PDB structures whose
classification field indicates that they are "membrane proteins" and the proteins
with Structural Classification of Proteins (SCOP) class-f domains. We evaluated
the relationships between these databases or datasets based on the overlap in
their contents and the degree of consistency in the structural, topological, and
functional classifications and in the transmembrane domain assignment. MAJOR
CONCLUSIONS: The membrane databases differ from each other in their coverage, and
in the criteria that they use for annotation and classification. To ensure the
efficient use of these databases, it is important to understand their differences
and similarities. The establishment of more detailed and consistent annotations
for the sequence, structure, membrane association, and function of membrane
proteins is still required. GENERAL SIGNIFICANCE: Considering the recent growth
of experimentally determined structures, a broad survey and cumulative analysis
of the sum of knowledge as presented in the membrane protein structure databases
can be helpful to elucidate structures and functions of membrane proteins. We
also aim to provide a framework for future research and classification of
membrane proteins.
PMID- 29331639
TI - Identification of the disinfection byproducts of bisphenol S and the disrupting
effect on peroxisome proliferator-activated receptor gamma (PPARgamma) induced by
chlorination.
AB - Bisphenol S (BPS), an alternative product to bisphenol A (BPA), has been the
focus of increasing public concern due to its potential endocrine disrupting
effect and its adverse effects related to metabolic disorders such as obesity.
The detection of its residue in drinking water supply systems suggests that BPS
can be chlorinated; however, whether its endocrine disrupting effect can be
disrupted by this chlorination remains unclear. In the present study, we
identified the byproducts of the reaction of BPS with chlorine and assessed the
effect of the main byproducts on peroxisome proliferator-activated receptor gamma
(PPARgamma). BPS was chlorinated in a simulation experiment. The chlorination
reaction in this study was chlorine and pH dependent, and the pseudo-first-order
reaction rate constant was controlled by the chlorine concentration and pH. The
reaction rate at pH 8.5 was 7 times faster than that at pH 6.5. Twenty-two
byproducts were putatively identified by liquid chromatography quadrupole time-of
flight mass spectrometry (LC-ESI-Q-ToF-MS), and five main byproducts were
purified and characterized by 1H and 13C nuclear magnetic resonance (NMR)
spectroscopy. The PPARgamma effects of the byproducts were assayed, revealing a2
to4-fold enhancement in their activities in comparison with the parent compound.
PMID- 29331640
TI - Recent advances in application of UV light-emitting diodes for degrading organic
pollutants in water through advanced oxidation processes: A review.
AB - Over the last decade, ultraviolet light-emitting diodes (UV LEDs) have attracted
considerable attention as alternative mercury-free UV sources for water treatment
purposes. This review is a comprehensive analysis of data reported in recent
years (mostly, post 2014) on the application of UV LED-induced advanced oxidation
processes (AOPs) to degrade organic pollutants, primarily dyes, phenols,
pharmaceuticals, insecticides, estrogens and cyanotoxins, in aqueous media.
Heterogeneous TiO2-based photocatalysis in lab grade water using UVA LEDs is the
most frequently applied method for treating organic contaminants. The effects of
controlled periodic illumination, different TiO2-based nanostructures and reactor
types on degradation kinetics and mineralization are discussed. UVB and UVC LEDs
have been used for photo-Fenton, photo-Fenton-like and UV/H2O2 treatment of
pollutants, primarily, in model aqueous solutions. Notably, UV LED-activated
persulfate/peroxymonosulfate processes were capable of providing degradation in
DOC-containing waters. Wall-plug efficiency, energy-efficiency of UV LEDs and the
energy requirements in terms of Electrical Energy per Order (EEO) are discussed
and compared. Despite the overall high degradation efficiency of the UV LED-based
AOPs, practical implementation is still limited and at lab scale. More research
on real water matrices at more environmentally relevant concentrations, as well
as an estimation of energy requirements providing fluence-based kinetic data are
required.
PMID- 29331641
TI - Enzymes from piezophiles.
AB - The discovery of microbial communities in extreme conditions that would seem
hostile to life leads to the question of how the molecules making up these
microbes can maintain their structure and function. While microbes that live
under extremes of temperature have been heavily studied, those that live under
extremes of pressure, or "piezophiles", are now increasingly being studied
because of advances in sample collection and high-pressure cells for biochemical
and biophysical measurements. Here, adaptations of enzymes in piezophiles against
the effects of pressure are discussed in light of recent experimental and
computational studies. However, while concepts from studies of enzymes from
temperature extremophiles can provide frameworks for understanding adaptations by
piezophile enzymes, the effects of temperature and pressure on proteins differ in
significant ways. Thus, the state of the knowledge of adaptation in piezophile
enzymes is still in its infancy and many more experiments and computational
studies on different enzymes from a variety of piezophiles are needed.
PMID- 29331642
TI - Protein adaptations in extremophiles: An insight into extremophilic connection of
mycobacterial proteome.
AB - The biological paradox about how extremophiles persist at extreme ecological
conditions throws a fascinating picture of the enormous potential of a single
cell to adapt to homeostatic conditions in order to propagate. Unicellular
organisms face challenges from both environmental factors and the ecological
niche provided by the host tissue. Although the existence of extremophiles and
their physiological properties were known for a long time, availability of whole
genome sequence has catapulted the study on mechanisms of adaptation and the
underlying principles that have enabled these unique organisms to withstand
evolutionary and environmental pressures. Comparative genomics has shown that
extremophiles possess the unique set of genes and proteins that empower them with
biochemical machinery necessary to thrive in extreme environments. The presence
of these proteins safeguards the cell against a wide array of extreme conditions
such as temperature, pressure, radiations, chemicals, drugs etc. An insight into
these adaptive mechanisms in extremophiles may help us to devise strategies to
alter the genes and proteins that may have therapeutic potential and commercial
value. Here we present an overview of the various adaptations in extremophiles.
We also try to explain how mycobacterium channelizes its proteome to survive in
stress conditions posed by host immune system.
PMID- 29331643
TI - Glucagon-like peptide 1 signaling inhibits allergen-induced lung IL-33 release
and reduces group 2 innate lymphoid cell cytokine production in vivo.
AB - BACKGROUND: IL-33 is one of the most consistently associated gene candidates for
asthma identified by using a genome-wide association study. Studies in mice and
in human cells have confirmed the importance of IL-33 in inducing type 2 cytokine
production from both group 2 innate lymphoid cells (ILC2s) and TH2 cells.
However, there are no pharmacologic agents known to inhibit IL-33 release from
airway cells. OBJECTIVE: We sought to determine the effect of glucagon-like
peptide 1 receptor (GLP-1R) signaling on aeroallergen-induced airway IL-33
production and release and on innate type 2 airway inflammation. METHODS: BALB/c
mice were challenged intranasally with Alternaria extract for 4 consecutive days.
GLP-1R agonist or vehicle was administered starting either 2 days before the
first Alternaria extract challenge or 1 day after the first Alternaria extract
challenge. RESULTS: GLP-1R agonist treatment starting 2 days before the first
Alternaria extract challenge decreased IL-33 release in the bronchoalveolar
lavage fluid and dual oxidase 1 (Duox1) mRNA expression 1 hour after the first
Alternaria extract challenge and IL-33 expression in lung epithelial cells 24
hours after the last Alternaria extract challenge. Furthermore, GLP-1R agonist
significantly decreased the number of ILC2s expressing IL-5 and IL-13, lung
protein expression of type 2 cytokines and chemokines, the number of perivascular
eosinophils, mucus production, and airway responsiveness compared with vehicle
treatment. GLP-1R agonist treatment starting 1 day after the first Alternaria
extract challenge also significantly decreased eosinophilia and type 2 cytokine
and chemokine expression in the airway after 4 days of Alternaria extract
challenge. CONCLUSION: These results reveal that GLP-1R signaling might be a
therapy to reduce IL-33 release and inhibit the ILC2 response to protease
containing aeroallergens, such as Alternaria.
PMID- 29331644
TI - Ozone exposure induces respiratory barrier biphasic injury and inflammation
controlled by IL-33.
AB - BACKGROUND: IL-33 plays a critical role in regulation of tissue homeostasis,
injury, and repair. Whether IL-33 regulates neutrophil recruitment and functions
independently of airways hyperresponsiveness (AHR) in the setting of ozone
induced lung injury and inflammation is unclear. OBJECTIVE: We sought to examine
the role of the IL-33/ST2 axis in lung inflammation on acute ozone exposure in
mice. METHODS: ST2- and Il33-deficient, IL-33 citrine reporter, and C57BL/6 (wild
type) mice underwent a single ozone exposure (1 ppm for 1 hour) in all studies.
Cell recruitment in lung tissue and the bronchoalveolar space, inflammatory
parameters, epithelial barrier damage, and airway hyperresponsiveness (AHR) were
determined. RESULTS: We report that a single ozone exposure causes rapid
disruption of the epithelial barrier within 1 hour, followed by a second phase of
respiratory barrier injury with increased neutrophil recruitment, reactive oxygen
species production, AHR, and IL-33 expression in epithelial and myeloid cells in
wild-type mice. In the absence of IL-33 or IL-33 receptor/ST2, epithelial cell
injury with protein leak and myeloid cell recruitment and inflammation are
further increased, whereas the tight junction proteins E-cadherin and zonula
occludens 1 and reactive oxygen species expression in neutrophils and AHR are
diminished. ST2 neutralization recapitulated the enhanced ozone-induced
neutrophilic inflammation. However, myeloid cell depletion using GR-1 antibody
reduced ozone-induced lung inflammation, epithelial cell injury, and protein
leak, whereas administration of recombinant mouse IL-33 reduced neutrophil
recruitment in Il33-deficient mice. CONCLUSION: Data demonstrate that ozone
causes an immediate barrier injury that precedes myeloid cell-mediated
inflammatory injury under the control of the IL-33/ST2 axis. Thus IL-33/ST2
signaling is critical for maintenance of intact epithelial barrier and
inflammation.
PMID- 29331645
TI - Realising the potential of various inhaled airway challenge agents through
improved delivery to the lungs.
AB - Inhaled airway challenges provoke bronchoconstriction in susceptible subjects and
are a pivotal tool in the diagnosis and monitoring of obstructive lung diseases,
both in the clinic and in the development of new respiratory medicines. This
article reviews the main challenge agents that are in use today (methacholine,
mannitol, adenosine, allergens, endotoxin) and emphasises the importance of
controlling how these agents are administered. There is a danger that the optimal
value of these challenge agents may not be realised due to suboptimal inhaled
delivery; thus considerations for effective and reproducible challenge delivery
are provided. This article seeks to increase awareness of the importance of
precise delivery of inhaled agents used to challenge the airways for diagnosis
and research, and is intended as a stepping stone towards much-needed
standardisation and harmonisation in the administration of inhaled airway
challenge agents.
PMID- 29331646
TI - Progress in the Management of Advanced Thoracic Malignancies in 2017.
AB - The treatment paradigm of NSCLC underwent a major revolution during the course of
2017. Immune checkpoint inhibitors (ICIs) brought remarkable improvements in
response and overall survival both in unselected pretreated patients and in
untreated patients with programmed death ligand 1 expression of 50% or more.
Furthermore, compelling preliminary results were reported for new combinations of
anti-programmed cell death 1/programmed death ligand 1 agents with chemotherapy
or anti-cytotoxic T-lymphocyte associated protein 4 inhibitors. The success of
the ICIs appeared to extend to patients with SCLC, mesothelioma, or thymic
tumors. Furthermore, in SCLC, encouraging activity was reported for an
experimental target therapy (rovalpituzumab teserine) and a new chemotherapeutic
agent (lurbinectedin). For oncogene-addicted NSCLC, next-generation tyrosine
kinase inhibitors (TKIs) (such as osimertinib or alectinib) have demonstrated
increased response rates and progression-free survival compared with first
generation TKIs in patients with both EGFR-mutated and ALK receptor tyrosine
kinase gene (ALK)-rearranged NSCLC. However, because of the lack of mature
overall survival data and considering the high efficacy of these drugs in
patients with NSCLC previously exposed to first- or second-generation TKIs,
definitive conclusions concerning the best treatment sequence cannot yet be
drawn. In addition, new oncogenes such as mutant BRAF, tyrosine-protein kinase
met gene (MET) and erb-b2 receptor tyrosine kinase 2 gene (HER2), and ret proto
oncogene (RET) rearrangements have joined the list of potential targetable
drivers. In conclusion, the field of thoracic oncology is on the verge of a
breakthrough that will open up many promising new therapeutic options for
physicians and patients. The characterization of biomarkers predictive of
sensitivity or resistance to immunotherapy and the identification of the optimal
therapeutic combinations (for ICIs) and treatment sequence (for oncogene-addicted
NSCLC) represent the toughest upcoming challenges in the domain of thoracic
oncology.
PMID- 29331647
TI - The implant effect after intracranial electrode placement: Is transient clinical
improvement explained by post-implantation electrophysiological changes?
PMID- 29331648
TI - Lung Ultrasound to Detect Residual Pneumothorax After Chest Drain Removal in Lung
Resections.
AB - BACKGROUND: Indication for postdrain removal imaging after lung resection is
debated. Chest roentgenogram (CR) is widely used to confirm lung expansion but
not evidence based. We propose to introduce lung ultrasound (LUS) as alternative
to exclude significant pneumothorax (PTx) in this setting. METHODS: The study
enrolled 50 patients undergoing lung resections. Inclusion criteria were complete
expansion of the lung at postoperative CR, pleural effusion of less than 300
mL/24 h, air leak of 10 to 20 mL/min for 6 hours. Two hours after chest drain
removal, LUS was performed at the second and third intercostal spaces to assess
pleural sliding. Patients with no detected PTx or with apical PTx were considered
for discharge. The same patients were blindly evaluated with CR by a second
operator, and a comparison between the two methods was performed. Clinical
decisions were taken based on CR results. RESULTS: LUS confirmed large PTxs in 7
patients, apical PTxs in 10 patients, and no PTx in 33 patients. CR confirmed 5
of 7 significant PTxs (1 chest drain reinserted, 4 patients observed), and 2 of 7
PTx were considered irrelevant. Apical PTxs were confirmed in 8 of 10 patients,
and in 2 patients there was no PTx at CR. The 33 patients with no PTx at LUS had
full lung expansion at CR. LUS has a negative predictive value of 100% in
excluding large PTxs and a positive predictive value of 71%. CONCLUSIONS: In this
subgroup of patients with air leak of 10 to 20 mL/min, performing an imaging
study to verify the absence of PTx is desirable; however, when LUS confirms lung
expansion or the presence of apical PTx, CR does not seem to be needed.
PMID- 29331649
TI - Friend or foe? Reactive oxygen species production, scavenging and signaling in
plant response to environmental stresses.
AB - In the natural environment, plants are exposed to a variety of biotic and abiotic
stress conditions that trigger rapid changes in the production and scavenging of
reactive oxygen species (ROS). The production and scavenging of ROS is
compartmentalized, which means that, depending on stimuli type, they can be
generated and eliminated in different cellular compartments such as the apoplast,
plasma membrane, chloroplasts, mitochondria, peroxisomes, and endoplasmic
reticulum. Although the accumulation of ROS is generally harmful to cells, ROS
play an important role in signaling pathways that regulate acclimatory and
defense responses in plants, such as systemic acquired acclimation (SAA) and
systemic acquired resistance (SAR). However, high accumulations of ROS can also
trigger redox homeostasis disturbance which can lead to cell death, and in
consequence, to a limitation in biomass and yield production. Different ROS have
various half-lifetimes and degrees of reactivity toward molecular components such
as lipids, proteins, and nucleic acids. Thus, they play different roles in intra-
and extra-cellular signaling. Despite their possible damaging effect, ROS should
mainly be considered as signaling molecules that regulate local and systemic
acclimatory and defense responses. Over the past two decades it has been proven
that ROS together with non-photochemical quenching (NPQ), hormones, Ca2+ waves,
and electrical signals are the main players in SAA and SAR, two physiological
processes essential for plant survival and productivity in unfavorable
conditions.
PMID- 29331650
TI - Echocardiographic patterns of postresuscitation myocardial dysfunction.
AB - BACKGROUND: Postresuscitation myocardial dysfunction (PRMD) can develop after
successful resuscitation from cardiac arrest. However, echocardiographic patterns
of PRMD remain unknown. This study aimed to investigate PRMD manifestations with
serial echocardiography during the post-cardiac arrest period. METHODS: We
enrolled non-traumatic out-of-hospital cardiac arrest patients older than 19
years who underwent successful cardiopulmonary resuscitation (CPR). We excluded
patients with myocardial infarction or pre-existing cardiac disease, including
heart failure or myocardial disease. Transthoracic echocardiography (TTE) was
performed within 24 h, between 24 and 48 h, and between 72 and 96 h after
restoration of spontaneous circulation (ROSC). RESULTS: Of 280 patients, 138 (93
men) were analysed. PRMD was observed in 45 patients (33%), including global
dysfunction in 28 patients (20%), regional wall motion abnormalities (RWMA) in 10
(7%), and Takotsubo pattern in 7 (5%). There were no differences in clinical
characteristics, laboratory findings, or hospital mortality according to PRMD
pattern. Global left ventricular (LV) systolic function gradually improved with
time and had recovered to normal by Day 3 in all patients except one with the
Takotsubo pattern, which remained on follow-up echocardiography two weeks after
ROSC. CONCLUSIONS: PRMD occurs in about one-third of patients resuscitated from
cardiac arrest. Echocardiographic patterns of post-cardiac arrest LV dysfunction
include global hypokinesia, regional wall motion abnormalities, and Takotsubo
pattern.
PMID- 29331651
TI - Activation of p62-keap1-Nrf2 antioxidant pathway in the early stage of
acetaminophen-induced acute liver injury in mice.
AB - Acetaminophen (APAP) overdose can cause severe liver failure even death. Nearly
half of drug-induced liver injury is attributed to APAP in the US and many
European countries. Oxidative stress has been validated as a critical event
involved in APAP-induced liver failure. p62/SQSTM1, a selective autophagy adaptor
protein, is reported to regulate Nrf2-ARE antioxidant pathway in response to
oxidative stress. However, the exact role of p62-keap1-Nrf2 antioxidant pathway
in APAP-induced hepatotoxicity remains unknown. In the present study, the dose
response and time-course model in C57/BL6 mice were established by
intraperitoneal injection of APAP. The results of serum alanine/aspartate
aminotransferases (ALT/AST) and histological examination demonstrated that APAP
overdose resulted in the severe liver injury. In the meantime, the levels of p62,
phospho-p62 and nuclear Nrf2 were significantly increased by APAP in mice liver,
suggesting an activation of p62-keap1-Nrf2 pathway. In addition, the expression
of GSTA1 mRNA was increased in a dose-dependent manner, while the mRNA levels of
HO-1 and GCLC were decreased with the increase of APAP dose. Our further
investigation found that expression of HO-1 and GCLC peaked at 3 h~6 h, and then
were decreased gradually. Taken together, these results indicated that p62-keap1
Nrf2 antioxidant pathway was primarily activated in the early stage of APAP
hepatotoxicity, which might play a protective role in the process of APAP-induced
acute liver injury.
PMID- 29331652
TI - Salinomycin induces primary chicken cardiomyocytes death via mitochondria
mediated apoptosis.
AB - Salinomycin, as a polyether ionophore antibiotic, is extensively used as a feed
additive against coccidiosis in poultry and as a growth promoter of ruminants
worldwide. Owing to its narrow therapeutic index, numerous intoxication have been
reported in target/non-target animals by overdosage, misuse or drug interactions
as well as human who consumed salinomycin accidently. Salinomycin-induced
cardiotoxicity in chicken and non-target animals is considered as a major
contributor to animal death. In the current study, we aim to elucidate the
underlying mechanism of its myocardial toxicity using primary chicken myocardial
cell as an in vitro model. The results showed that salinomycin altered cellular
morphology and induced cell death in a concentration-dependent manner.
Salinomycin treatment elevated the permeability of the cell membrane and leaded
to the efflux of enzymes, including creatine kinase (CK) and lactate
dehydrogenase (LDH). Flow cytometry analysis indicated the number of apoptotic
cells increased significantly by salinomycin exposure. Furthermore, caspase-3 and
caspase-9 were activated at gene and protein level rather than caspase-8, along
with the up-regulation of apoptosis genes Bax, Cytochrome C, Apoptotic peptidase
activating factor 1 (Apaf-1) and the down-regulation of Bcl-2. Salinomycin
induced mitochondrial dysfunction was accompanied by the significant decrease of
mitochondrial membrane potential (MMP) and the severe ultrastructure damage. In
conclusion, these findings suggest that the toxic dose of salinomycin induces
severe cardiomyocytes death through mitochondria mediated apoptosis pathway.
PMID- 29331653
TI - Gallic acid attenuates type I diabetic nephropathy in rats.
AB - Literature suggests that TGF-beta1 has a central role in the progression of
diabetic nephropathy and its down regulation can improve the disease condition.
Oxidative stress, generation of advanced glycation end products and activation of
renin angiotensin system are the connecting links between hyperglycemia and TGF
beta1 over expression. Gallic acid is a phytochemical having wide range of
biological activities. Gallic acid is reported to have antioxidant and advanced
glycation inhibitory activity. It has also shown inhibitory effects on
angiotensin converting enzyme. Gallic acid qualifies as a drug candidate to be
tested in the diabetic nephropathy, one of the important complication of
diabetes. Streptozotocin (55 mg/kg body weight, i.p.) induced diabetic
nephropathy was used as an experimental model. Gallic acid was evaluated for its
possible effect at the dose of 20 and 40 mg/kg body weight. Gallic acid treatment
significantly lowered plasma levels of the creatinine and blood urea nitrogen and
elevated the levels of the protein and albumin. Gallic acid also improved
creatinine clearance. Determination of oxidative stress parameters showed that
the oxidative stress in kidney tissues was reduced significantly in gallic acid
treated animals. Results of the plasma, urine and oxidative stress parameters
were also reflected in the histopathological evaluation showing improvement in
kidney pathophysiology. ELISA assay for circulating TGF-beta1 evaluation and
immunohistochemical study for determination of kidney expression of TGF-beta1
revealed that gallic acid significantly lowered both the circulating and tissue
levels of TGF-beta1. Results support the hypothesis that gallic acid can be
effectively used in the treatment of diabetic nephropathy.
PMID- 29331654
TI - In vitro and in vivo metabolic activation of rhein and characterization of
glutathione conjugates derived from rhein.
AB - Rhein (RH), 4,5-dihydroxyanthrauinone-2-carboxylic acid, is found in rhubarb
(Dahuang), a traditional herbal medicine. RH has reportedly demonstrated multiple
pharmacologic properties. Previous studies have also shown that RH induced
hepatotoxicity, but the mechanisms of the adverse effect remain unknown. The
major objective of the present study was to study the metabolic pathways of RH in
order to identify potential reactive metabolites. One mono-hydroxylation
metabolite (M1) was detected in urine and bile of rats given RH. M1 was also
observed in rat and human liver microsomal incubations after exposure to RH. A
total of three (GSH) conjugates (M2, M3 and M5) were detected in bile of rats
treated with RH. We concluded that M2-M3 were directly derived from parent
compound RH through spontaneous reaction with GSH. M5 was derived from M1 by
reaction with GSH, which required cytoslic GSTs. M5 was further metabolized to
the corresponding NAC conjugate (mercapturic acid) and was excreted in urine.
P450 2C9 was mainly involved in the oxidation of RH.
PMID- 29331655
TI - What makes it so difficult for nurses to coach patients in shared decision
making? A process evaluation.
AB - BACKGROUND: Primary care nurses play a crucial role in coaching patients in
shared decision making about goals and actions. This presents a challenge to
practice nurses, who are frequently used to protocol-based working routines.
Therefore, an approach was developed to support nurses to coach patients in
shared decision making. OBJECTIVES: To investigate how the approach was
implemented and experienced by practice nurses and patients. DESIGN: A process
evaluation was conducted using quantitative and qualitative methods.
SETTINGS/PARTICIPANTS: Fifteen female practice nurses (aged between 28 and 55
years), working with people suffering from diabetes, COPD, asthma and/or
cardiovascular diseases, participated. Nurses were asked to apply the approach to
their chronically ill patients and to recruit patients (n = 10) willing to
participate in an interview or an audio-recording of a consultation (n = 13);
patients (13 women, 10 men) were aged between 41 and 88 years and suffered from
diabetes, COPD or cardiovascular diseases. METHODS: The approach involved a
framework for shared decision making about goals and actions, a tool to explore
the patient perspective, a patient profiles model and a training course.
Interviews (n = 15) with nurses, a focus group with nurses (n = 9) and interviews
with patients (n = 10) were conducted. Nurses filled in a questionnaire about
their work routine before, during and after the training course. They were asked
to deliver audiotapes of their consultations (n = 13). RESULTS: Overall, nurses
felt that the approach supported them to coach patients in shared decision
making. Nurses had become more aware of their own attitudes and learning needs
and reported to have had more in-depth discussions with patients. The on-the-job
coaching was experienced as valuable. However, nurses struggled to integrate the
approach in routine care. They experienced the approach as different to their
protocol-based routines and expressed the importance of receiving support and the
need for integration of the approach into the family physician practice.
CONCLUSION: This study shows that changing practice nurses' role from medical
experts to coaches in shared decision making is very complex and requires paying
attention to skills and attitudes, as well as to contextual factors. Our results
indicate that more time and training might be needed for this role transition.
Moreover, it might be worthwhile to focus on organizational learning, in order to
increase an organization's capacity to change work routines in a collaborative
process. Future research into the development and evaluation of health coaching
approaches, focusing on shared decision making, is necessary.
PMID- 29331656
TI - Effect of a wearable patient sensor on care delivery for preventing pressure
injuries in acutely ill adults: A pragmatic randomized clinical trial (LS-HAPI
study).
AB - IMPORTANCE: Though theoretically sound, studies have failed to demonstrate the
benefit of routine repositioning of at-risk patients for the prevention of
hospital acquired pressure injuries. OBJECTIVE: To assess the clinical
effectiveness of a wearable patient sensor to improve care delivery and patient
outcomes by increasing the total time with turning compliance and preventing
pressure injuries in acutely ill patients. DESIGN: Pragmatic, investigator
initiated, open label, single site, randomized clinical trial. SETTING: Two
Intensive Care Units in a large Academic Medical Center in California.
PARTICIPANTS: Consecutive adult patients admitted to one of two Intensive Care
Units between September 2015 to January 2016 were included (n = 1564). Of the
eligible patients, 1312 underwent randomization. INTERVENTION: Patients received
either turning care relying on traditional turn reminders and standard practices
(control group, n = 653), or optimal turning practices, influenced by real-time
data derived from a wearable patient sensor (treatment group, n = 659). MAIN
OUTCOME(S) AND MEASURE(S): The primary and secondary outcomes of interest were
occurrence of hospital acquired pressure injury and turning compliance.
Sensitivity analysis was performed to compare intention-to-treat and per-protocol
effects. RESULTS: The mean age was 60 years (SD, 17 years); 55% were male. We
analyzed 103,000 h of monitoring data. Overall the intervention group had
significantly fewer Hospital Acquired Pressure Injuries during Intensive Care
Unit admission than the control group (5 patients [0.7%] vs. 15 patients [2.3%]
(OR = 0.33, 95%CI [0.12, 0.90], p = 0.031). The total time with turning
compliance was significantly different in the intervention group vs. control
group (67% vs 54%; difference 0.11, 95%CI [0.08, 0.13], p < 0.001). Turning
magnitude (21 degrees , p = 0.923) and adequate depressurization time (39%, p =
0.145) were not statistically different between groups. CONCLUSIONS AND
RELEVANCE: Among acutely ill adult patients requiring Intensive Care Unit
admission, the provision of optimal turning was greater with a wearable patient
sensor, increasing the total time with turning compliance and demonstrated a
statistically significant protective effect against the development of hospital
acquired pressure injuries. These are the first quantitative data on turn quality
in the Intensive Care Unit and highlight the need to reinforce optimal turning
practices. Additional clinical trials leveraging technologies like wearable
sensors are needed to establish the appropriate frequency and dosing of
individualized turning protocols to prevent pressure injuries in at-risk
hospitalized patients.
PMID- 29331657
TI - Views of teenage children about the effects of a Parent's mobility disability.
AB - BACKGROUND: Few U.S. studies have explored how children experience a parent's
mobility disability and its effects on their daily lives. OBJECTIVE: We aimed to
engage youth ages 13-17 who had at least one parent with mobility disability in
describing their perceptions of their parent's disability and its consequences
for their daily and family life. METHODS: Participants videoed and photographed
their experiences following general guidelines from the researchers about topics
of interest. Participants made their own choices about what they submitted. We
used conventional content analysis to identify broad themes. RESULTS: The mean
(standard deviation) age of the 10 participants was 15.2 (1.9) years; 5 were
male; 9 participants were white. All 5 girls submitted multiple self-focused
(selfie) videos made in their bedrooms; the 5 boys submitted more diverse data
files. Several broad themes or topics emerged including: the effects of timing
and trajectory of the parent's disability; perceptions of early maturity and
responsibility; fears and frustrations relating to the parent's disability;
support and emerging resilience; and sense of social justice. Participants
generally felt their parents' disability made them become - compared to their
peers - more mature, responsible, capable of performing household tasks, and
aware of disability civil rights. CONCLUSIONS: Participants raised many issues
that health care providers should be aware of when youth have parents with
mobility disability. A parent's mobility disability may be associated with
resilience but also may pose challenges for youth. More research is needed to
understand better adolescents' experiences and how clinicians might best assist
these youth.
PMID- 29331659
TI - Mindfulness-related differences in neural response to own infant negative versus
positive emotion contexts.
AB - Mindfulness is thought to promote well-being by shaping the way people respond to
challenging social-emotional situations. Current understanding of how this occurs
at the neural level is based on studies of response to decontextualized emotion
stimuli that may not adequately represent lived experiences. In this study, we
tested relations between mothers' dispositional mindfulness and neural responses
to their own infant in different emotion-eliciting contexts. Mothers (n = 25)
engaged with their 3-month-old infants in videorecorded tasks designed to elicit
negative (arm restraint) or positive (peekaboo) emotion. During a functional MRI
session, mothers were presented with 15-s clips from these recordings, and
dispositional mindfulness scores were used to predict their neural responses to
arm restraint > peekaboo videos. Mothers higher in nonreactivity showed
relatively lower activation to their infants' arm restraint compared to peekaboo
videos in hypothesized regions-insula and dorsal prefrontal cortex-as well as non
hypothesized regions. Other mindfulness dimensions were associated with more
limited areas of lower (nonjudgment) and higher (describing) activation in this
contrast. Mothers who were higher in mindfulness generally activated more to the
positive emotion context and less to the negative emotion context in perceptual
and emotion processing areas, a pattern that may help to explain mindfulness
related differences in well-being.
PMID- 29331658
TI - Sulforaphene Enhances The Efficacy of Photodynamic Therapy In Anaplastic Thyroid
Cancer Through Ras/RAF/MEK/ERK Pathway Suppression.
AB - Sulforaphene (SFE), a natural isothiocyanate from cruciferous vegetables has
shown a potential anticancer effect against cervical and lung cancer. Palliative
treatments like photodynamic therapy (PDT) are being implemented for a long time
however, the results are still not promising in case of aggressive cancers like
anaplastic thyroid cancer. The objective of this work is to establish an
alternative method with the combination of photofrin-PDT and sulforaphene, a
natural isothiocyanate from cruciferous vegetables, against human anaplastic
thyroid cancer to enhance the efficacy of PDT. In this study, cell viability of
FRO cells due to combination treatment was analyzed by MTT assay, Cell cycle
arrest, MMP depolarization and ROS generation, analyzed by flow cytometry.
Western blot analysis of various proliferative proteins was performed to assess
the activity of combination treatment against FRO cells. From the results,
sulforaphene alone showed no cytotoxicity against normal cells, however,
combination of sulforaphene and photofrin mediated PDT showed a noticeable
decrease in cell proliferation against FRO cells. Combination treatment
synergistically caused cell cycle arrest via ROS generation and MMP
depolarization. The expressions of Ras, MEK, ERK, B-Raf proteins significantly
modulated due to combination treatment. PDT and SFE can induce apoptosis in
anaplastic thyroid cancer cells individually but while treated in combination, it
enhanced the apoptotic and anti-proliferative effect, much higher than the
individual doses. In summary, our work designates sulforaphene as a unique
natural enhancer of efficacy with PDT against anaplastic thyroid cancer.
PMID- 29331660
TI - Persistent contamination of heater-cooler units for extracorporeal circulation
cured by chlorhexidine-alcohol in water tanks.
AB - Recently, surgical site infections due to non-tuberculous mycobacteria (NTM) have
been linked to heater-cooler unit contamination. The European Centre for Disease
Prevention and Control and manufacturers now recommend the use of hydrogen
peroxide in filtered water to fill heater-cooler unit tanks. After implementation
of these measures in our hospital, heater-cooler units became heavily
contaminated by opportunistic waterborne pathogens such as Pseudomonas aeruginosa
and Stenotrophomonas maltophilia. No NTM were detected but fast-growing resistant
bacteria could impair their detection. The efficiency of hydrogen peroxide and
chlorhexidine-alcohol was compared in situ. Chlorhexidine-alcohol treatment
stopped waterborne pathogen contamination and NTM were not cultured whereas their
detection efficiency was probably improved.
PMID- 29331661
TI - Effect of LaF3: Ag fluorescent nanoparticles on photodynamic efficiency and
cytotoxicity of Protoporphyrin IX photosensitizer.
AB - LaF3: Ag nanoparticles (NPs) were synthesized by the co-precipitation method. The
produced NPs were characterized by X-ray diffraction (XRD) pattern, scanning
electron microscope (SEM), dynamic light scattering (DLS) and Fourier transform
infrared spectroscopy (FTIR). The emission spectrum of LaF3:Ag NPs is mostly
overlapped with the absorption band of protoporphyrin IX (PpIX) and their
conjugation was confirmed by studying fluorescence resonance energy transfer
(FRET) from LaF3:Ag donor to protoporphyrin IX acceptor. The energy transfers
from LaF3:Ag NPs to photosensitizer molecules is very efficient. So, the produced
LaF3:Ag NPs can be recommended as light source for photodynamic therapy (PDT).
The thiol group of cysteine was bound to LaF3:Ag NPs in order to conjugate
LaF3:Ag NPs and protoporphyrin IX. UVC light source was used to excite
fluorescent LaF3:Ag NPs. The reactive oxygen species (ROS) produced by
photosensitizer was identified using special fluorescent probes (anthracene,
methylene blue and methyl orange) as detectors.
PMID- 29331662
TI - Exposure to natural environments, and photographs of natural environments,
promotes more positive body image.
AB - Five studies were conducted to understand the impact of nature exposure on body
image. In three studies using different designs and outcome measures, British
university students were exposed to photographs of natural or built environments.
Results indicated that exposure to images of natural, but not built, environments
resulted in improved state body image. In Study 4, British community participants
went on a walk in a natural or built environment, with results indicating that
the walk in a natural environment resulted in significantly higher state body
appreciation, whereas the walk in a built environment resulted in significantly
lower scores. In Study 5, British participants were recruited as they were
entering a designed green space on their own volition. Results indicated that
spending time in the green space led to improved state body appreciation. These
results indicate that exposure to isomorphic or in-situ natural environments has
positive effects on state body image.
PMID- 29331663
TI - A Multicenter Randomized Trial to Evaluate Hematologic Toxicities after
Hyperthermic Intraperitoneal Chemotherapy with Oxaliplatin or Mitomycin in
Patients with Appendiceal Tumors.
AB - BACKGROUND: Appendiceal cancer is a rare disease that has proven difficult to
study in prospective trials. Cytoreductive surgery with hyperthermic
intraperitoneal chemotherapy (HIPEC) is an established therapy for peritoneal
dissemination from appendiceal cancer. The optimal chemotherapeutic agent to use
in the HIPEC is not clear. Mitomycin has long been used, however, our previous
phase I experience and European retrospective studies suggest oxaliplatin as an
alternative. Therefore, we initiated a multicenter randomized trial to compare
mitomycin with oxaliplatin HIPEC for appendiceal cancer. STUDY DESIGN: Patients
with mucinous appendiceal neoplasms with evidence of peritoneal dissemination
underwent cytoreductive surgery and HIPEC using a closed technique for 120
minutes. Patients were randomized intraoperatively to HIPEC using mitomycin (40
mg) or oxaliplatin (200 mg/M2). Follow-up included daily blood counts and
toxicity assessments. RESULTS: One hundred and twenty-one analytic patients were
accrued to the trial during 6 years at 3 sites. The patients were 57% female,
with a mean age of 55.3 years (range 22 to 82 years). The disease was low grade
in 77% and high grade in 23%. There were no significant differences in hemoglobin
or platelet counts. The WBC was significantly lower in the mitomycin group
between postoperative days 5 and 10. Overall and disease-free survival rates at 3
years were similar at 83.7% and 66.8% for mitomycin and 86.9% and 64.8% for
oxaliplatin. CONCLUSIONS: This represents the first completed prospective
randomized trial for cancer of the appendix, and shows that multicenter trials
for this disease are feasible. Both mitomycin and oxaliplatin are associated with
minor hematologic toxicity. However, mitomycin has slightly higher hematologic
toxicity and lower quality of life than oxaliplatin in HIPEC. Consequently,
oxaliplatin might be preferred in patients with leukopenia and mitomycin
preferred in patients with thrombocytopenia due to earlier chemotherapy.
PMID- 29331664
TI - Children exhibit different performance patterns in explicit and implicit theory
of mind tasks.
AB - Three studies tested scope and limits of children's implicit and explicit theory
of mind. In Studies 1 and 2, three- to six-year-olds (N = 84) were presented with
closely matched explicit false belief tasks that differed in whether or not they
required an understanding of aspectuality. Results revealed that children
performed equally well in the different tasks, and performance was strongly
correlated. Study 3 tested two-year-olds (N = 81) in implicit interactive
versions of these tasks and found evidence for dis-unity: children performed
competently only in those tasks that did not require an understanding of
aspectuality. Taken together, the present findings suggest that early implicit
and later explicit theory of mind tasks may tap different forms of cognitive
capacities.
PMID- 29331665
TI - Blocking LPA-dependent signaling increases ovarian cancer cell death in response
to chemotherapy.
AB - The paradoxical role of reactive oxygen species in cell death versus cell
survival establishes a delicate balance between chemotherapy efficacy and
management of detrimental side effects. Normal proliferative signaling requires
that cells remain inside a redox range that allows reversible protein oxidation
to occur. Shifting the redox environment toward highly reducing or oxidizing
states leads to cellular stress and cell death. Reactive oxygen species produced
in response to Taxol and cisplatin treatment are necessary for effective cancer
cell killing but the same ROS leads to damaging side effects in normal tissues.
Combining antioxidants with chemotherapeutics to alleviate the unwanted side
effects produces variable and often undesirable effects on cancer treatment.
Here, we describe a more targeted method to improve ovarian cancer cell killing
without the need for antioxidants. In ovarian cancer cells, lysophosphatidic acid
(LPA) is a prominent growth factor that contributes to tumor survival and
proliferation. We find that blocking LPA-dependent signaling with a specific
receptor antagonist consistently increases cell death in response to both Taxol
and cisplatin. We propose that inhibiting the upregulated growth factor-dependent
signaling in cancer cells will target chemo-insensitivity, potentially lowering
the necessary dose of the drugs and preventing harmful side effects.
PMID- 29331667
TI - Vitamin D suppresses macrophage infiltration by down-regulation of TREM-1 in
diabetic nephropathy rats.
AB - This study intends to investigate the effect of active vitamin D (VD) on the
expression of triggering receptor expressed on myeloid cells-1 (TREM-1) in the
renal tissues of diabetic nephropathy (DN) rats and to explore the impact of TREM
1 on macrophage adhesion and migration. We find that the expressions of TREM-1
and CD68 protein are higher in DN rats compared with rats in the normal control
group and that these changes are decreased in the DN + VD group. In vitro, the
capacity for macrophage adhesion and migration and the expression of TREM-1 are
increased under high-glucose conditions, but VD inhibits this progress. TREM-1
siRNA decreases high-glucose-induced macrophage adhesion and migration, whereas
over-expression of TREM-1 inhibits its action. However, VD cannot suppress high
glucose-induced TREM-1 expression and macrophage adhesion and migration when TREM
1 is over-expressed. These results demonstrate that VD can suppress macrophage
adhesion and migration by reducing the expression of TREM-1.
PMID- 29331668
TI - Earlier and enhanced rehabilitation of mechanically ventilated patients in
critical care: A feasibility randomised controlled trial.
AB - BACKGROUND: Systematic reviews of early rehabilitation within intensive care
units have highlighted the need for robust multi-centre randomised controlled
trials with longer term follow up. This trial aims to explore the feasibility of
earlier and enhanced rehabilitation for patients mechanically ventilated for
>=5days and to assess the impact on possible long term outcome measures for use
in a definitive trial. METHODS: Patients admitted to a large UK based intensive
care unit and invasively ventilated for >=5days were randomised to the
rehabilitation intervention or standard care on a 1:1 basis, stratified by age
and SOFA score. The rehabilitation intervention involved a structured programme,
with progression along a functionally based mobility protocol according to set
safety criteria. RESULTS: 103 out of 128 eligible patients were recruited into
the trial, achieving an initial recruitment rate of 80%. Patients in the
intervention arm mobilized significantly earlier (8days vs 10 days, p=0.035), at
a more acute phase of illness (SOFA 6 vs 4, p<0.05) and reached a higher level of
mobility at the point of critical care discharge (MMS 7 vs 5, p<0.01).
CONCLUSION: We have demonstrated the feasibility of introducing a structured
programme of rehabilitation for patients admitted to critical care.
PMID- 29331666
TI - Age-related oxidative changes in pancreatic islets are predominantly located in
the vascular system.
AB - Aged tissues usually show a decreased regenerative capacity accompanied by a
decline in functionality. During aging pancreatic islets also undergo several
morphological and metabolic changes. Besides proliferative and regenerative
limitations, endocrine cells lose their secretory capacity, contributing to a
decline in functional islet mass and a deregulated glucose homeostasis. This is
linked to several features of aging, such as induction of cellular senescence or
the formation of modified proteins, such as advanced glycation end products
(AGEs) - the latter mainly examined in relation to hyperglycemia and in disease
models. However, age-related changes of endocrine islets under normoglycemic and
non-pathologic conditions are poorly investigated. Therefore, a characterization
of pancreatic tissue sections as wells as plasma samples of wild-type mice
(C57BL/6J) at various age groups (2.5, 5, 10, 15, 21 months) was performed. Our
findings reveal that mice at older age are able to secret sufficient amounts of
insulin to maintain normoglycemia. During aging the pancreatic islet area
increased and the islet size doubled in 21 months old mice when compared to 2.5
months old mice, whereas the islet number was unchanged. This was accompanied by
an age-dependent decrease in Ki-67 levels and pancreatic duodenal homeobox-1 (PDX
1), indicating a decline in proliferative and regenerative capacity of pancreatic
islets with advancing age. In contrast, the number of p16Ink4a-positive nuclei
within the islets was elevated starting from 10 months of age. Interestingly,
AGEs accumulated exclusively in the islet blood vessels of old mice associated
with increased amounts of inflammatory markers, such as the inducible nitric
oxide synthase (iNOS) and 3-nitrotyrosine (3-NT). In summary, the age-related
increase in islet size and area was associated with the induction of senescence,
accompanied by an accumulation of non-enzymatically modified proteins in the
islet vascular system.
PMID- 29331669
TI - Acinetobacter baumannii ST317 can be identified with Martins' trilocus sequence
based multiplex-PCR.
PMID- 29331670
TI - Circulation of Alphacoronavirus, Betacoronavirus and Paramyxovirus in
Hipposideros bat species in Zimbabwe.
AB - Bats carry a great diversity of zoonotic viruses with a high-impact on human
health and livestock. Since the emergence of new coronaviruses and
paramyxoviruses in humans (e.g. Severe Acute Respiratory Syndrome Coronavirus
(SARS-CoV) and Nipah virus), numerous studies clearly established that bats can
maintain some of these viruses. Improving our understanding on the role of bats
in the epidemiology of the pathogens they harbour is necessary to prevent cross
species spill over along the wild/domestic/human gradient. In this study, we
screened bat faecal samples for the presence of Coronavirus and Paramyxovirus in
two caves frequently visited by local people to collect manure and/or to hunt
bats in Zimbabwe. We amplified partial RNA-dependent RNA polymerase genes of
Alpha and Betacoronavirus together with the partial polymerase gene of
Paramyxovirus. Identified coronaviruses were related to pathogenic human strains
and the paramyxovirus belonged to the recently described Jeilongvirus genus. Our
results highlighted the importance of monitoring virus circulation in wildlife,
especially bats, in the context of intense human-wildlife interfaces in order to
strengthen prevention measures among local populations and to implement sentinel
surveillance in sites with high zoonotic diseases transmission potential.
PMID- 29331671
TI - The molecular characteristics of avian influenza viruses (H9N2) derived from air
samples in live poultry markets.
AB - OBJECTIVE: To study the molecular characteristics of H9N2-subtype avian influenza
viruses (AIVs) isolated from air samples collected in live poultry markets (LPMs)
and explore their sequence identities with AIVs that caused human infection.
METHODS: Weekly surveillance of H9N2-subtype AIVs in the air of LPMs was
conducted from 2015 to 2016. H9-positive samples were isolated from chicken
embryos. Whole genome sequences of the isolated AIVs were obtained through high
throughput sequencing. Phylogenetic analysis and key loci variations of the
sequences were further analyzed. RESULTS: A total of 327 aerosol samples were
collected from LPMs. Nine samples were positive for H9-subtype AIVs based on
quantitative real-time reverse transcription polymerase chain reaction (qRRT
PCR). According to the whole genome sequence analysis and phylogenetic analysis,
except for the A/Environment/Zhongshan/ZS201505/2015 (ZS201505) strain, 8 gene
segments of 8 aerosol H9N2 isolates and 2 H9N2 human isolates in 2015 were
located in the same clade. Among key loci variations, except for the ZS201505
strain, H9N2-subtype AIVs had no mutations in eight receptor binding sites of
hemagglutinin (HA), and stalks of neuraminidase (NA) proteins exhibited a
deletion site of three bases. The PA gene of ZS201503 and ZS201602 exhibited an
L336M mutation. The N30D and T215A mutations in the M1 gene and amino acid
residues L89V in PB2, P42S in NS1 and S31N in M2 were retained in these 9 strains
of H9N2 isolates, which could enhance the virus's virulence. CONCLUSION: Live
H9N2 AIVs survived in the aerosol of LPMs in Zhongshan City. The aerosol viruses
had a close evolutionary relationship with human epidemic strains, indicating
that there might be a risk of AIV transmission from polluted aerosols in LPMs to
humans. Mutations in H9N2-subtype AIVs isolated from air samples collected from
LPMs suggested their pathogenicity was enhanced to infect humans.
PMID- 29331672
TI - Breast cancer screening: Where have we been and where are we going? A personal
perspective based on history, data and experience.
AB - It is important to understand the history of breast cancer screening to better
understand the continuing effort to reduce access to screening. Since the
randomized, controlled trials have shown a statistically significant mortality
reduction for women ages 40-74, the appropriate threshold for initiating
screening is age 40 with no data to support the use of the age of 50 as a
threshold for screening. All women are at risk for developing breast cancer and
all women should have access to screening.
PMID- 29331673
TI - Diversity of Aspergillus section Nigri on the surface of Vitis labrusca and its
hybrid grapes.
AB - This study investigated the presence of Aspergillus species belonging to
Aspergillus section Nigri on Vitis labrusca and its hybrid grapes grown in
Brazil. The ability of the fungi isolates to produce ochratoxin A (OTA) and
fumonisin B2 (FB2) as well as the presence of these mycotoxins in the grapes were
also studied. Eighty-eight samples were collected from the main grape producing
states in Brazil: Rio Grande do Sul (n=30), Pernambuco (n=21), Sao Paulo (n=21)
and Parana (n=16). The highest average contamination level by A. section Nigri
occurred on the grapes from Pernambuco (66.3%). A total of 2042 A. section Nigri
isolates was analyzed and clustered in three groups according to morphology
characterization: A. section Nigri uniseriate (79.3%), A. niger "aggregate"
(18.3%) and A. carbonarius (2.4%). In order to precisely identify the Aspergillus
species, two hundred and forty-eight strains were subjected to DNA sequencing.
Among the A. section Nigri uniseriate group, the following species were found: A.
japonicus, A. uvarum, A. brunneoviolaceus, A. aculeatus and A. labruscus. Within
the A. niger "aggregate", the following species were found: A.niger sensu
stricto, A. welwitschiae and A. vadensis. Regarding mycotoxin-production
capacity, 3.2% of the total A. section Nigri isolates (2042) were positive for
OTA production and from A. niger "aggregate" (373) tested, 42.1% were FB2
producers. However, none of the 88 grape samples were contaminated with these
mycotoxins.
PMID- 29331674
TI - HIV Activates the Tyrosine Kinase Hck to Secrete ADAM Protease-Containing
Extracellular Vesicles.
PMID- 29331676
TI - Identification of novel amino acid residues of influenza virus PA-X that are
important for PA-X shutoff activity by using yeast.
AB - The influenza A virus protein PA-X comprises an N-terminal PA region and a C
terminal PA-X-specific region. PA-X suppresses host gene expression, termed
shutoff, via mRNA cleavage. Although the endonuclease active site in the N
terminal PA region of PA-X and basic amino acids in the C-terminal PA-X-specific
region are known to be important for PA-X shutoff activity, other amino acids may
also play a role. Here, we used yeast to identify novel amino acids of PA-X that
are important for PA-X shutoff activity. Unlike wild-type PA-X, most PA-X mutants
predominantly localized in the cytoplasm, indicating that these mutations
decreased the shutoff activity of PA-X by affecting PA-X translocation to the
nucleus. Mapping of the identified amino acids onto the N-terminal structure of
PA revealed that some of them likely contribute to the formation of the
endonuclease active site of PA.
PMID- 29331675
TI - Module Analysis Captures Pancancer Genetically and Epigenetically Deregulated
Cancer Driver Genes for Smoking and Antiviral Response.
AB - : The availability of increasing volumes of multi-omics profiles across many
cancers promises to improve our understanding of the regulatory mechanisms
underlying cancer. The main challenge is to integrate these multiple levels of
omics profiles and especially to analyze them across many cancers. Here we
present AMARETTO, an algorithm that addresses both challenges in three steps.
First, AMARETTO identifies potential cancer driver genes through integration of
copy number, DNA methylation and gene expression data. Then AMARETTO connects
these driver genes with co-expressed target genes that they control, defined as
regulatory modules. Thirdly, we connect AMARETTO modules identified from
different cancer sites into a pancancer network to identify cancer driver genes.
Here we applied AMARETTO in a pancancer study comprising eleven cancer sites and
confirmed that AMARETTO captures hallmarks of cancer. We also demonstrated that
AMARETTO enables the identification of novel pancancer driver genes. In
particular, our analysis led to the identification of pancancer driver genes of
smoking-induced cancers and 'antiviral' interferon-modulated innate immune
response. SOFTWARE AVAILABILITY: AMARETTO is available as an R package at
https://bitbucket.org/gevaertlab/pancanceramaretto.
PMID- 29331677
TI - Identification of Potential MR-Derived Biomarkers for Tumor Tissue Response to
177Lu-Octreotate Therapy in an Animal Model of Small Intestine Neuroendocrine
Tumor.
AB - Magnetic resonance (MR) methods enable noninvasive, regional tumor therapy
response assessment, but associations between MR parameters, underlying biology,
and therapeutic effects must be investigated. The aim of this study was to
investigate response assessment efficacy and biological associations of MR
parameters in a neuroendocrine tumor (NET) model subjected to radionuclide
treatment. Twenty-one mice with NETs received 177Lu-octreotate at day 0. MR
experiments (day -1, 1, 3, 8, and 13) included T2-weighted, dynamic contrast
enhanced (DCE) and diffusion-weighted imaging (DWI) and relaxation measurements
(T1/T2*). Tumor tissue was analyzed using proteomics. MR-derived parameters were
evaluated for each examination day and for different radial distances from the
tumor center. Response assessment efficacy and biological associations were
evaluated using feature selection and protein expression correlations,
respectively. Reduced tumor growth rate or shrinkage was observed until day 8,
followed by reestablished growth in most tumors. The most important MR parameter
for response prediction was DCE-MRI-derived pretreatment signal enhancement ratio
(SER) at 40% to 60% radial distance, where it correlated significantly also with
centrally sampled protein CCD89 (association: DNA damage and repair,
proliferation, cell cycle arrest). The second most important was changed
diffusion (D) between day -1 and day 3, at 60% to 80% radial distance, where it
correlated significantly also with peripherally sampled protein CATA
(association: oxidative stress, proliferation, cell cycle arrest, apoptotic cell
death). Important information regarding tumor biology in response to radionuclide
therapy is reflected in several MR parameters, SER and D in particular. The
spatial and temporal information provided by MR methods increases the sensitivity
for tumor therapy response.
PMID- 29331678
TI - MicroRNA-320 Enhances Radiosensitivity of Glioma Through Down-Regulation of
Sirtuin Type 1 by Directly Targeting Forkhead Box Protein M1.
AB - Glioma is the most common cancer in human brain system and seriously threatens
human health. miRNA-320 has been demonstrated to be closely correlated with the
development of glioma. However, its effect and molecular mechanism underlying
radioresistance have not been fully elucidated in glioma. Here, RT-qPCR assay was
used to assess the expressions of miR-320 and forkhead box protein M1 (FoxM1)
mRNA in glioma tumor tissues and cells. The effects of miR-320, FoxM1 and sirtuin
type 1 (Sirt1) on radiosensitivity in glioma cells were evaluated by clone
formation assay, apoptosis assay, histone H2AX phosphorylation level (gammaH2AX)
detection and caspase 3 activity analysis, respectively. The direct interaction
between miR-320 and FoxM1 was detected by luciferase assay. The protein levels of
FoxM1, Sirt1 and gammaH2AX were measured by western blot assay. We found that miR
320 expression was down-regulated and FoxM1 expression was up-regulated in
radioresistant glioma tissues and IR-treated glioma cells. miR-320 overexpression
dramatically enhanced radiosensitivity, promoted apoptosis, and improved
gammaH2AX expression and caspase 3 activity in glioma cells. Luciferase reporter
assay and western blot assay further validated that miR-320 suppressed FoxM1
expression by directly targeting 3' UTR region of FoxM1. Moreover, miR-320
inhibited Sirt1 expression via targeting FoxM1 in glioma cells. Furthermore,
overexpression of FoxM1 and Sirt1 strikingly attenuated miR-320-induced increase
of radiosensitivity, apoptosis and gammaH2AX expression in glioma cells. In
conclusion, miR-320 enhanced radiosensitivity of glioma cells through down
regulation of Sirt1 by directly targeting FoxM1.
PMID- 29331679
TI - Molecular identification of forensically important calliphoridae and
sarcophagidae species using ITS2 nucleotide sequences.
AB - The application of insect evidence to forensic investigations is mainly based on
the estimation of postmortem interval and the identification of insect species
from samples that are collected from the crime scene. Due to the limited number
of expert taxonomists, species identification is one of the major barriers for
crime scene investigators to utilize forensic entomology. Therefore, the
molecular identification of species, using mitochondrial cytochrome c oxidase
subunit I (COI) gene, has been suggested as an alternative strategy. However, in
some cases, these maternally inherited markers cause confusion; hence, nuclear
DNA markers such as ITS2 are also required as supporting tools. Eleven
Calliphoridae and 5 Sarcophagidae fly species collected from Korea were utilized
for PCR amplification and nucleotide sequencing of ITS2 locus. Species Identifier
software was used for sequence analysis and comparison. The results demonstrated
that 11 Korean Calliphoridae and 5 Korean Sarcophagidae fly species could be
distinguished using ITS2 nucleotide sequences. In particular, the sister species,
Lucilia illustris and Lucilia caesar were also distinguished, despite the very
low level of interspecific diversity. However, when compared with previously
reported ITS2 nucleotide sequences, several identification failures were noted.
This is the first study that widely analyzed nucleotide sequences of the ITS2
locus from Calliphoridae and Sarcophagidae fly species collected in Korea.
PMID- 29331681
TI - Endogenous cortisol in keratinized matrices: Systematic determination of baseline
cortisol levels in hair and the influence of sex, age and hair color.
AB - The measurement of hair cortisol is increasingly used to measure long-term
cumulative cortisol levels and investigate its role as an important stress
mediator. In this study a comparative statistical analysis of five independent
studies (all analyzed in our laboratory) was performed to investigate baseline
ranges of cortisol values in hair and evaluate potential influences of sex, age
and hair color. Cortisol concentrations in hair of 554 subjects were measured and
a comparative statistical analysis was performed. The analysis showed that
cortisol levels significantly differ depending on age. The toddler group (7
months (0.6 years) to 3 years) showed significantly higher values (median
10pg/mg, p-value<0.0001, d=0.78) than the adolescent group. The adolescent groups
showed significantly lower (p-value<0.0001, d=0.58 and p<0.0001, d=0.13) values
(median 2.4pg/mg and 2.8pg/mg) than the adult group (median 5.8pg/mg).
Furthermore, in the adult group men showed significantly higher cortisol values
than women (p-value<0.05, d=0.17). This effect could not be seen in the
adolescent group. Black hair showed higher cortisol concentrations than blond
hair (p-value<0.0001, d=1.3). In addition, two rounds of interlaboratory
comparisons for hair cortisol samples between four laboratories revealed very
consistent results. Our results demonstrate that baseline cortisol levels are
generally low in hair thus making a standardized and well-elaborated analytical
method indispensable for accurate determination. Age-dependent normative baseline
cortisol levels (toddlers, adolescents and adults) are highly recommended based
on the comparative analysis comprising five independent studies.
PMID- 29331680
TI - Estimating error rates for firearm evidence identifications in forensic science.
AB - Estimating error rates for firearm evidence identification is a fundamental
challenge in forensic science. This paper describes the recently developed
congruent matching cells (CMC) method for image comparisons, its application to
firearm evidence identification, and its usage and initial tests for error rate
estimation. The CMC method divides compared topography images into correlation
cells. Four identification parameters are defined for quantifying both the
topography similarity of the correlated cell pairs and the pattern congruency of
the registered cell locations. A declared match requires a significant number of
CMCs, i.e., cell pairs that meet all similarity and congruency requirements.
Initial testing on breech face impressions of a set of 40 cartridge cases fired
with consecutively manufactured pistol slides showed wide separation between the
distributions of CMC numbers observed for known matching and known non-matching
image pairs. Another test on 95 cartridge cases from a different set of slides
manufactured by the same process also yielded widely separated distributions. The
test results were used to develop two statistical models for the probability mass
function of CMC correlation scores. The models were applied to develop a
framework for estimating cumulative false positive and false negative error rates
and individual error rates of declared matches and non-matches for this
population of breech face impressions. The prospect for applying the models to
large populations and realistic case work is also discussed. The CMC method can
provide a statistical foundation for estimating error rates in firearm evidence
identifications, thus emulating methods used for forensic identification of DNA
evidence.
PMID- 29331682
TI - Post mortem tryptase cut-off level for anaphylactic death.
AB - Serum mast cell tryptase is used to support the diagnosis of anaphylaxis. The
recommended clinical cut-off for total tryptase (<11.4MUg/L) appears unsuitable
in the post mortem setting due to largely unknown processes which result in
significantly elevated levels in these samples. Consequently there is no widely
accepted tryptase cut-off level for diagnosing an anaphylactic death. This 5-year
retrospective study compared total tryptase levels in post mortem femoral blood
in anaphylactic deaths and control. Univariate and multivariate analysis was used
to assess the relative contribution of other factors (age, gender, post mortem
interval, and presence of resuscitation) on post mortem tryptase levels. Nine
anaphylactic deaths and 45 controls were identified. Receiver-operating
characteristic (ROC) curve analysis identified an optimal cut-off of 53.8MUg/L,
with sensitivity of 89%, and specificity of 93%, for total post mortem tryptase
in femoral blood to diagnosis anaphylaxis. No other factors showed any
statistical significant contribution to post mortem tryptase elevation. Femoral
total post mortem tryptase level of 53.8MUg/L and above is a useful ancillary
test in diagnosing an anaphylactic death.
PMID- 29331683
TI - Appropriate fossil calibrations and tree constraints uphold the Mesozoic
divergence of solenodons from other extant mammals.
AB - The mammalian order Eulipotyphla includes four extant families of insectivorans:
Solenodontidae (solenodons); Talpidae (moles); Soricidae (shrews); and
Erinaceidae (hedgehogs). Of these, Solenodontidae includes only two extant
species, which are endemic to the largest islands of the Greater Antilles: Cuba
and Hispaniola. Most molecular studies suggest that eulipotyphlan families
diverged from each other across several million years, with the basal split
between Solenodontidae and other families occurring in the Late Cretaceous. By
contrast, Sato et al. (2016) suggest that eulipotyphlan families diverged from
each other in a polytomy ~58.6 million years ago (Mya). This more recent
divergence estimate for Solenodontidae versus other extant eulipotyphlans
suggests that solenodons must have arrived in the Greater Antilles via overwater
dispersal rather than vicariance. Here, we show that the young timetree estimates
for eulipotyphlan families and the polytomy are due to an inverted ingroup
outgroup arrangement of the tree, the result of using Tracer rather than
TreeAnnotator to compile interfamilial divergence times, and of not enforcing the
monophly of well-established clades such as Laurasiatheria and Eulipotyphla.
Finally, Sato et al.'s (2016) timetree includes several zombie lineages where
estimated divergence times are much younger than minimum ages that are implied by
the fossil record. We reanalyzed Sato et al.'s (2016) original data with enforced
monophyly for well-established clades and updated fossil calibrations that
eliminate the inference of zombie lineages. Our resulting timetrees, which were
compiled with TreeAnnotator rather than Tracer, produce dates that are in good
agreement with other recent studies and place the basal split between
Solenodontidae and other eulipotyphlans in the Late Cretaceous.
PMID- 29331684
TI - Reprogramming neurodegeneration in the big data era.
AB - Recent genome-wide association studies (GWAS) have identified numerous genetic
risk variants for late-onset Alzheimer's disease (AD) and Parkinson's disease
(PD). However, deciphering the functional consequences of GWAS data is
challenging due to a lack of reliable model systems to study the genetic variants
that are often of low penetrance and non-coding identities. Pluripotent stem cell
(PSC) technologies offer unprecedented opportunities for molecular phenotyping of
GWAS variants in human neurons and microglia. Moreover, rapid technological
advances in whole-genome RNA-sequencing and epigenome mapping fuel comprehensive
and unbiased investigations of molecular alterations in PSC-derived disease
models. Here, we review and discuss how integrated studies that utilize PSC
technologies and genome-wide approaches may bring new mechanistic insight into
the pathogenesis of AD and PD.
PMID- 29331685
TI - Nucleic adaptability of heterokaryons to fungicides in a multinucleate fungus,
Sclerotinia homoeocarpa.
AB - Sclerotinia homoeocarpa is the causal organism of dollar spot in turfgrasses and
is a multinucleate fungus with a history of resistance to multiple fungicide
classes. Heterokaryosis gives rise to the coexistence of genetically distinct
nuclei within a cell, which contributes to genotypic and phenotypic plasticity in
multinucleate fungi. We demonstrate that field isolates, resistant to either a
demethylation inhibitor or methyl benzimidazole carbamate fungicide, can form
heterokaryons with resistance to each fungicide and adaptability to serial
combinations of different fungicide concentrations. Field isolates and putative
heterokaryons were assayed on fungicide-amended media for in vitro sensitivity.
Shifts in fungicide sensitivity and microsatellite genotypes indicated that
heterokaryons could adapt to changes in fungicide pressure. Presence of both
nuclei in heterokaryons was confirmed by detection of a single nucleotide
polymorphism in the beta-tubulin gene, the presence of microsatellite alleles of
both field isolates, and the live-cell imaging of two different fluorescently
tagged nuclei using laser scanning confocal microscopy. Nucleic adaptability of
heterokaryons to fungicides was strongly supported by the visualization of
changes in fluorescently labeled nuclei to fungicide pressure. Results from this
study suggest that heterokaryosis is a mechanism by which the pathogen adapts to
multiple fungicide pressures in the field.
PMID- 29331686
TI - Quercetin decrease somatic cells count in mastitis of dairy cows.
AB - Quercetin is a dietary flavonoid which has an effect on inflammation,
angiogenesis and vascular inflammation. In several other flavonoids (e.g.
kaempferol, astragalin, alpinetin, baicalein, indirubin), anti-inflammatory
mechanism was proven by using mice mastitis model. The aim of the current study
was pilot analysis of quercetin tolerability and its impact on somatic cells
count (SCC) after multiple intramammary treatment on dairy cows with clinical
mastitis. Based on SCC and clinical investigation, 9 dairy cows with clinical
mastitis of one quarter were selected for the pilot study. Baseline analysis
(hematology, TNFalpha, SCC) was performed every 24h among all cows three days
before the first dose (B1-B3). After the baseline monitoring (B1-B3) eight days
treatment (D1-D8) was performed with a high and low dose. Selected blood
parameters were analyzed. Starting from D1 to D8, a decrease of SCC in relation
to baseline was characterized by declining trend. The presented results allowed
the confirmation of the significant influence of quercetin on the reduction of
SCC in mastitis in dairy cows after 8days of therapy.
PMID- 29331687
TI - Probiotics Bacillus toyonensis and Saccharomyces boulardii improve the vaccine
immune response to Bovine herpesvirus type 5 in sheep.
AB - There have been significant efforts toward the development of more efficient
vaccines for animal health. A strategy that may be used to improve vaccine
efficacy is the use of probiotics. Bovine herpesvirus 5 (BoHV-5) is an example of
an important animal pathogen for which vaccines have provided only limited
protection. In this study, we examined the use of the probiotics Bacillus
toyonensis and Saccharomyces boulardii as a potential immune modulator to improve
vaccine efficiency. Thirty, 5-month-old lambs were randomly grouped in three lots
of 10 each and vaccinated at days 0, 21 and 42 of the experiment. They grazed on
the same pasture and were fed ad libitum twice a day with commercial sheep feed
supplemented with either B. toyonensis (1*106CFU/g of feed) or S. boulardii
(1*107CFU/g of feed), or non-supplemented feed. The probiotic supplementation was
suspended day 28; thereafter, the next 35days, they were fed with the same
commercial feed as control group. Animals supplemented with probiotics showed a
significant (p>0.001) increased seroconversions against BoHV-5, and higher
neutralizing antibodies titres (p>0.05) to BoHV-5 than non-supplemented animals.
At 63days of experiment, splenocytes from the supplemented sheep had higher mRNA
transcription levels of cytokines IL-10 and IL-17A. These results suggest that
these probiotics could provide a promising means of improving vaccine efficacy.
PMID- 29331688
TI - Coproheme decarboxylases - Phylogenetic prediction versus biochemical
experiments.
AB - Coproheme decarboxylases (ChdCs) are enzymes responsible for the catalysis of the
terminal step in the coproporphyrin-dependent heme biosynthesis pathway.
Phylogenetic analyses confirm that the gene encoding for ChdCs is widespread
throughout the bacterial world. It is found in monoderm bacteria (Firmicutes,
Actinobacteria), diderm bacteria (e. g. Nitrospirae) and also in Archaea. In
order to test phylogenetic prediction ChdC representatives from all clades were
expressed and examined for their coproheme decarboxylase activity. Based on
available biochemical data and phylogenetic analyses a sequence motif (-Y-P-M/F-X
K/R-) is defined for ChdCs. We show for the first time that in diderm bacteria an
active coproheme decarboxylase is present and that the archaeal ChdC homolog from
Sulfolobus solfataricus is inactive and its physiological role remains elusive.
This shows the limitation of phylogenetic prediction of an enzymatic activity,
since the identified sequence motif is equally conserved across all previously
defined clades.
PMID- 29331689
TI - Baicalin inhibits pressure overload-induced cardiac fibrosis through regulating
AMPK/TGF-beta/Smads signaling pathway.
AB - AMP-activated protein kinase (AMPK) is a central regulator of multiple metabolic
pathways. It has been shown that activation of AMPK could inhibit fibroblast
proliferation and extracellular matrix (ECM) accumulation, thereby suppressing
cardiac fibrosis. Baicalin, the major component found in skullcap, possesses
multiple protective effects on the cardiovascular system. However, little is
known about the effect of baicalin on cardiac fibrosis and the molecular
mechanism by which baicalin exerts its anti-fibrotic effects has not been
investigated. In this study, we revealed that baicalin could inhibit cell
proliferation, collagen synthesis, fibronectin (FN) and Connective tissue growth
factor (CTGF) protein expression in cardiac fibroblasts induced by angiotensin II
(Ang II). It also ameliorated cardiac fibrosis in rats submitted to abdominal
aortic constriction (AAC). Moreover, baicalin inhibited transforming growth
factor-beta (TGF-beta)/Smads signaling pathway stimulated with Ang II through
activating AMPK. Subsequently, we also demonstrated that baicalin attenuated Ang
II-induced Smad3 nuclear translocation, and interaction with transcriptional
coactivator p300, but promoted the interaction of p300 and AMPK. Taken together,
these results provide the first evidence that the effect of baicalin against
cardiac fibrosis may be attributed to its regulation on AMPK/TGF-beta/Smads
signaling, suggesting the therapeutic potential of baicalin on the prevention of
cardiac fibrosis and heart failure.
PMID- 29331690
TI - Effect of depressive symptoms on the evolution of neuropsychological functions
over the course of adolescence.
AB - INTRODUCTION: Comprehensive understanding of the association between depression
and neuropsychological functioning over the course of adolescence requires
developmentally sensitive assessment through longitudinal data. The aim of
current study is to examine the concurrent and subsequent effects of depressive
symptoms on the initial level and evolution of four neuropsychological
functioning domains (i.e., spatial working memory, delayed recall memory,
perceptual reasoning, and inhibitory control). METHOD: Depressive symptoms and
neuropsychological functioning were assessed over the course of four years in a
sample of 3826 Canadian adolescents. A series of multilevel models estimated the
between-person, within-person, and lagged within-person effects of depressive
symptoms on each domain of neuropsychological functioning. RESULTS: Findings
suggest that current year and past year depressive symptoms were associated with
poorer performance in delayed recall memory and perceptual reasoning tasks.
Likewise, past year depressive symptoms were associated with poorer spatial
working memory performance. These detrimental effects were stronger in early
adolescence. LIMITATIONS: The current study examined the presence of sub-clinical
depressive symptoms but not clinical depression. Moreover, although depressive
symptoms and neuropsychological functions were assessed using widely used, valid,
and reliable computer-based instruments, the results may not match the accuracy
of clinician-based assessments. CONCLUSIONS: Our results underline the necessity
of early intervention for young adolescents to decrease the harms associated with
depression. The effect of early-onset depression on the underlying neural
substrates of neuropsychological functioning merits further investigation.
PMID- 29331691
TI - Design limitations to bipolar II treatment efficacy studies: A challenge and a
revisionist strategy.
AB - BACKGROUND: Trials examining medication efficacy for bipolar II disorder commonly
employ a set of standardized interval measures to assess outcomes. The key issue
is whether such interval measures pick up changes in the severity, duration and
frequency of depressive, hypomanic and euthymic episodes. METHOD: We examine the
application of measures most commonly used to monitor progress in nine studies
involving participants with a bipolar II disorder and published in journals with
a moderate to high impact factor. RESULTS: Studies rarely provided interval
details for assessing depressive and hypomanic symptoms. None specified whether
ratings of depressive and hypomanic symptoms were based on severity, duration or
number of symptoms, and none recorded any data on euthymic periods. LIMITATIONS:
Our sample of reviewed studies was small and our analyses focused only on the
three most commonly used outcome measures. We advocate for complementary
subjective daily mood monitoring strategies but recognize that such strategies
need to be validated in future studies. CONCLUSIONS: We argue that interval
ratings undertaken weekly or over longer periods may compromise efficacy data. We
recommend that userguides be developed to ensure standard outcome measures are
employed consistently across trials, and that specific details be published in
trial papers about how measures were employed and what mood episode
characteristics were measured at each assessment. We also argue for daily ratings
to be used as an outcome measure to provide data on severity, frequency and
duration of depressive, hypomanic and euthymic periods in intervention studies of
those with a bipolar II disorder.
PMID- 29331693
TI - Disease management apps and technical assistance systems for bipolar disorder:
Investigating the patients' point of view.
AB - BACKGROUND: Smartphone-based disease management has become increasingly
interesting for research in the field of bipolar disorders. This article
investigates the attitudes of persons affected by this disorder towards the
appropriation of mobile apps or assistance systems for the management of their
disease. METHODS: We conducted two separate studies. Study 1 was an online survey
with 88 participants. In study 2 we consulted 15 participants during a semi
structured interview. All the participants had formerly been diagnosed with
bipolar disorder. RESULTS: More than half of the participants of study 1 and most
participants of study 2 agreed with the use of an app or assistance system for
self-ratings, third party ratings and an objective symptom monitoring. Potential
interventions that were popular in both groups included a regular feedback, the
visualization of monitored data and advice in crises. LIMITATIONS: With study 1
we were not able to ensure correct diagnoses or to interact in a flexible way. In
Study 2 those issues were resolved, but the small number of participants raises
the question of a possible generalisability of the results. Furthermore, for both
studies a selection bias could not be excluded. CONCLUSIONS: Our results indicate
positive attitudes of bipolar patients towards disease management apps and
assistance systems. Even new and innovative features such as partner apps or the
analysis of facial expressions in video data were appreciated and daily
interactions were favoured. However, the variety of answers calls for flexible
systems which allow activating or deactivating certain features.
PMID- 29331692
TI - Memory performance predicts response to psychotherapy for depression in bipolar
disorder: A pilot randomized controlled trial with exploratory functional
magnetic resonance imaging.
AB - OBJECTIVE: This pilot randomized controlled trial compared Cognitive Behavior
Therapy (CBT) and Supportive Psychotherapy (SP) for the treatment of depression
in bipolar I disorder. We also examined whether exploratory verbal memory,
executive functioning, and neural correlates of verbal memory during functional
magnetic resonance imaging (fMRI) predicted change in depression severity.
METHODS: Thirty-two adults (ages 18-65) with DSM-IV bipolar I disorder meeting
current criteria for a major depressive episode were randomized to 18 weeks of
CBT or SP. Symptom severity was assessed before, at the mid-point, and after the
18-week intervention. All participants completed a brief pre-treatment
neuropsychological testing battery (including the California Verbal Learning Test
2nd Edition, Delis Kaplan Executive Functioning System [DKEFS] Trail-making Test,
and DKEFS Sorting Test), and a sub-set of 17 participants provided usable fMRI
data while completing a verbal learning paradigm that consisted of encoding word
lists. RESULTS: CBT and SP yielded comparable improvement in depressive symptoms
from pre- to post-treatment. Better retention of learned information (CVLT-II
long delay free recall vs. Trial 5) and recognition (CVLT-II hits) were
associated with greater improvement in depression in both treatments. Increased
activation in the left dorsolateral prefrontal cortex and right hippocampus
during encoding was also related to depressive symptom improvement. LIMITATIONS:
Sample size precluded tests of clinical factors that may interact with
cognitive/neural function to predict treatment outcome. CONCLUSION:
Neuropsychological assessment and fMRI offer additive information regarding who
is most likely to benefit from psychotherapy for bipolar depression.
PMID- 29331694
TI - Distinctive use of newer and older antidepressants in major geographical areas: A
nationally representative register-based study.
AB - BACKGROUND: It is unknown whether newer, mainly selective serotonin reuptake
inhibitors, and older tricyclic antidepressants are used similarly regardless of
the geographical area of residence and education. METHODS: We included four
randomly sampled cohorts of the Finnish working aged population (n = 998,540
1,033,135). The sampling (Dec 31st in 1995, 2000, 2004 and 2010) resulted in non
overlapping time windows where each participant was followed up for four years
for the first antidepressant use. Using Cox proportional hazards models, we
examined whether the hazard of antidepressant use differed between the capital
area and three other areas (Southern, Western and Northern/Eastern Finland).
Educational differences were examined using four sub-groups: capital area/high
education (reference category); other areas/high education; capital area/low
education; and other areas/low education. RESULTS: Hazard ratios for the use of
newer antidepressants were significantly lower in all other areas compared to the
capital area after adjustment for age, sex, marital status, employment status,
education, income, and area-level unemployment. Findings remained consistent in
all time windows, differences increasing slightly. In the sub-group analysis
those with low education had the lowest level of use in all areas, also within
the capital area. The results were opposite for older antidepressants in all but
the last time window. LIMITATIONS: Some degree of unmeasured confounding and
exposure misclassification is likely to exist. CONCLUSIONS: Newer antidepressants
were more commonly used in the capital than in the other areas, and among those
with high versus low education. These differences in antidepressant use suggest
socioeconomic inequalities in the mental health treatment quality.
PMID- 29331695
TI - Depression and playfulness in fathers and young infants: A matched design
comparison study.
AB - BACKGROUND: Depression in fathers in the postnatal period is associated with an
increased risk of some adverse child developmental outcomes. One possible
mechanism for the familial transmission of risk is through the negative effects
of depression on parenting and the parent-child relationship. So far, evidence
indicates that depressed fathers tend to be more withdrawn in their early
interactions. However, the interaction dimensions studied to date may not be able
to detect and accurately classify unique features of father-infant play -
including physically stimulating and highly rousing episodes of play. Hence, in
this matched design comparison study, we set out to examine, for the first time,
links between diagnosed paternal depression in the postnatal period and
playfulness in father-infant interactions. METHODS: Fathers and their infants
were assessed when the infants were 3 months old. Paternal depression was
diagnosed using a structured psychiatric interview. Currently depressed (n = 19)
and non-depressed (n = 19) fathers were individually matched on age and
education. Fathers were filmed playing with their children. Four dimensions were
coded for paternal playfulness during free-play: physicality, playful excitation,
tactile stimulation and active engagement. RESULTS: Depressed fathers, compared
to non-depressed fathers, engaged in fewer episodes of playful excitation (mean
scores: 0.71 vs.2.53, p = 0.005), less gentle touch (mean time: 38.57 vs. 53.37,
p = 0.015) and less active engagement (mean scores: 2.29 vs 3.24, p = 0.044).
When controlling for infant fretfulness, the findings remained largely unchanged.
LIMITATIONS: The sample size was small and the sample was limited to mostly
white, well-educated fathers. CONCLUSIONS: Playful paternal behaviours as early
as 3 months differ between fathers with and without depression. These changes may
help in understanding children's risk in relation to paternal psychopathology and
could be a target for future family interventions.
PMID- 29331696
TI - Does early response predict subsequent remission in bipolar depression treated
with repeated sleep deprivation combined with light therapy and lithium?
AB - BACKGROUND: The combination of three cycles of sleep deprivation (SD), light
therapy (LT), and lithium has recently been proposed as a possible first-line
treatment for bipolar depression. However, it is unclear whether early
improvement predicts final response/remission in bipolar depression treated with
this regimen. METHOD: We studied 220 consecutively admitted inpatients with a
major depressive episode in the course of bipolar disorder. The relation between
response to first SD and response/remission at the end of the treatment (day 6)
was analyzed using logistic regression analysis. Severity of depression was rated
using the Hamilton Depression Rating Scale (HDRS). Clinical response was defined
as a >=50% reduction in HDRS scores, and remission was defined as an HDRS score
of <=7. RESULTS: Among the 217 completers, 67.7% showed response and 54.4%
reached remission at the end of the treatment. Multiple logistic regression
analysis revealed that response after first recovery sleep (day 2) predicted
final response and remission at the end of the treatment with high odds ratios
(10.9 for response and 8.2 for remission); however, response immediately after
the first SD (day 1) did not predict final response or remission. LIMITATIONS:
Whether our results can be generalized to unipolar depression remains uncertain.
CONCLUSION: Clinical status after first recovery sleep is a strong predictor of
successful final outcome in patients with bipolar depression treated with the
combination of repeated SD, LT, and lithium. Recovery sleep may play a role in
inducing the antidepressant effect associated with the success of treatment.
PMID- 29331697
TI - Longitudinal trajectories of post-traumatic stress disorder (PTSD) after birth
and associated risk factors.
AB - BACKGROUND: Although longitudinal trajectories of post-traumatic stress disorder
(PTSD) are well-established in general trauma populations, very little is known
about the trajectories of birth-related PTSD. This study aimed to identify
trajectories of birth-related PTSD; determine factors associated with each
trajectory; and identify women more likely to develop birth-related PTSD. METHOD:
226 women who had traumatic childbirth according to DSM-IV criterion A were drawn
from a community sample of 950 women. Measures were taken of PTSD, affective
symptoms, fear of childbirth and social support in pregnancy, 4-6 weeks and 6
months postpartum. Information on some obstetric and psychosocial factors were
also prospectively obtained. RESULTS: Four trajectories were identified:
resilience (61.9%), recovery (18.5%), chronic-PTSD (13.7%) and delayed-PTSD
(5.8%). Resilience was consistently distinguished from other PTSD trajectories by
less affective symptoms at 4-6 weeks postpartum. Poor satisfaction with health
professionals was associated with chronic-PTSD and delayed-PTSD. When affective
symptoms at 4-6 weeks postpartum were removed from the model, less social support
and higher fear of childbirth 4-6 weeks after birth predicted chronic and
recovery trajectories; whereas experience of further trauma and low levels of
satisfaction with health professionals were predictive of chronic-PTSD and
delayed-PTSD, compared to resilience. Additional variables associated with
different trajectories included antenatal affective symptoms, caesarean-section,
preterm birth and receiving professional help. LIMITATIONS: Use of self-report
measures, use of DSM-IV criteria for PTSD diagnosis, and no follow-up beyond six
months are the main limitations of this study. CONCLUSION: Identified factors may
inform preventive and treatment interventions for women with traumatic birth
experiences.
PMID- 29331698
TI - Exploring metabolic factors and health behaviors in relation to suicide attempts:
A case-control study.
AB - BACKGROUND: Suicide attempts are a serious public health concern with devastating
global impact, thereby necessitating the development of an adequate prevention
strategy. Few known risk factors of suicide attempts are directly modifiable.
This study sought to investigate potential associations between health behaviors
and suicide attempts, identifying novel opportunities for clinicians to help
prevent suicidal behavior. METHODS: A case-control study was conducted to compare
body weight, serum total cholesterol, physical activity, tobacco use, and dietary
food groups among adults who had made a suicide attempt (n = 84) to psychiatric
inpatients (n = 104) and community controls (n = 93) without history of suicide
attempt. Multivariable binary logistic regression analyses were used to
investigate the association between metabolic risk factors and attempted suicide.
RESULTS: Psychiatric inpatients who had attempted suicide were less likely to be
physically active [moderate/strenuous (OR 0.42, 95% CI 0.19-0.95) and mild (OR
0.35, 95% CI 0.16-0.76)] compared to controls. Psychiatric inpatients who
attempted suicide were more likely to use tobacco (OR 2.25, 95% CI 1.07-4.73)
compared to controls. Contrary to prior research, obesity, serum total
cholesterol, and diet were not significantly associated with risk of attempted
suicide. LIMITATIONS: Our study was limited by its cross-sectional design, which
precludes the identification of causal or temporal relationships between the risk
of attempted suicide and factors such as physical activity and tobacco use.
CONCLUSIONS: Study results suggest that a history of attempted suicide is
associated with a decreased likelihood of being physically active and an
increased risk of tobacco use. Further investigation is warranted to understand
the role of exercise and tobacco use in suicide intervention and prevention
strategies.
PMID- 29331699
TI - Simultaneous social causation and social drift: Longitudinal analysis of
depression and poverty in South Africa.
AB - BACKGROUND: Two theories have been proposed to explain the observed association
between depression and poverty, namely social causation and social drift. Little
is known regarding the relative importance of social causation and social drift
in low and middle-income countries, where poverty is more severe and where most
of the world's depressed individuals live. METHODS: We analysed nationally
representative longitudinal data from the National Income Dynamics Study in South
Africa and simultaneously tested social causation and social drift hypotheses
using structural equation modelling across three waves. RESULTS: Worse individual
economic status at time 1 and 2 was independently associated with worse
depression two years later at time 2 (standardised linear regression coefficient
beta = -0.110, Standard Error (SE): 0.024) and four years later at time 3 (beta =
-0.113, SE: 0.025) respectively. Conversely worse depression at time 1 and time 2
was independently associated with worse economic status at time 2 (beta = -0.037,
SE: 0.016) and time 3 (beta = -0.028, SE: 0.012) respectively. In addition, the
"effect" of depression on future assets was stronger among people with less
baseline assets. LIMITATIONS: The time span between data rounds is relatively
short (four years); response rates are unequal across ethnic, age and sex groups;
and the measure of depression is based on self-report. CONCLUSIONS: Social
causation and social drift act simultaneously in this population, reinforcing
poverty/depression cycles. Multi-sectoral policies are required that both prevent
depression by addressing its economic determinants, and provide evidence-based
treatment to mitigate the economic impact of depression.
PMID- 29331700
TI - Effects of macrophage migration inhibitory factor on cardiac reperfusion injury
in mice with depression induced by constant-darkness.
AB - RATIONALE: Depression is associated with coronary artery disease and increases
adverse outcomes and mortality in patients with acute myocardial infarction, but
the underlying pathophysiological mechanisms remain unclear. OBJECTIVE: To
evaluate the effect of macrophage migration inhibitory factor (MIF) on cardiac
ischemia-reperfusion (I/R) injury in mice with constant darkness-induced
depression. METHODS AND RESULTS: Twenty C57BL/6 mice (8 weeks old, male) were
randomly divided into 2 groups: one group was housed in a 12h light/dark cycle
environment (LD) and the other in a constant darkness environment (DD). After 3
weeks, constant darkness-exposed (DD) mice displayed depression-like behavior as
indicated by increased immobility in the forced swim test (FST) and lower sucrose
preference rate. Western blotting revealed cardiac MIF expression was
significantly lower in the DD mice than that in the LD mice. Next, 84 mice were
randomly divided into 4 groups: LD sham group, LD I/R group, DD sham group, and
DD I/R group. Following ischemia and reperfusion, mice in the DD I/R group had a
larger infarct area and lower heart function index than mice in the LD I/R group
(P < 0.05 for both). The cardiac pAMPK and pACC expression levels of the DD I/R
group were also lower in the DD I/R group (P < 0.05). CONCLUSION: DD-induced
depression might cause decreased expression of MIF in the heart, resulting in
downregulation of MIF-AMPK signaling and a subsequent adverse outcome after a
cardiac I/R injury.
PMID- 29331701
TI - The use of triiodothyronine (T3) in the treatment of bipolar depression: A review
of the literature.
AB - BACKGROUND: There is a paucity of treatment options for bipolar depression. The
use of triiodothyronine (T3) has been suggested as adjunctive treatment. METHODS:
A search on Medline, Limo and ScienceDirect was performed using the search terms
bipolar disorder, bipolar depression, treatment resistant, treatment refractory,
thyroid hormones, triiodothyronine, T3, acceleration and augmentation. RESULTS:
We retrieved three open studies, one comparative study, two double blind and one
retrospective chart review. The three open studies observed improvement in
respectively 56%, 75% and 79% of patients, the retrospective chart review noted
improvement in 89% of cases and the mirror design showed improvement in 66%. In
the comparative study T3 performed significantly better than placebo. The only
randomized double blind study could not prove any substantial difference between
T3 and placebo. LIMITATIONS: Available studies are scarce and flawed. All have
(very) low number of subjects: overall, only 353 subjects and only 194 of which
in prospective trials. In only two of the prospective trials bipolar patients
were analyzed separately. Comparing the studies is hampered by a high variability
in assessment tools, baseline medication and degree of treatment-resistance.
CONCLUSIONS: The few available studies are small and flawed. They do show
promising results. We found many clues suggesting that T3 could augment and
accelerate treatment response not only with antidepressants, but also with
lithium and perhaps with other treatment options, that it might protect against
rapid cycling bipolar disorder, as well as against relapse during the first few
years of treatment.
PMID- 29331702
TI - Is very low infant birth weight a predictor for a five-year course of depression
in parents? A latent growth curve model.
AB - BACKGROUND: A very low birth weight (VLBW) is considered as a significant risk
factor for early-onset developmental problems in infants, but is also discussed
as a potential risk factor for the development of depressive symptoms in affected
parents. METHODS: In this study, the 5-year courses of maternal and paternal
depression with VLBW and term born infants (n = 250 families) are modeled and
predicted by factors existing at the time of birth. RESULTS: The dyadic
trajectories of depression could be best described by five classes (I no
depression, II minor maternal depression, III increasing dyadic depression, IV
significant maternal depression, V highly depressed mothers). VLBW was a
significant predictor for the course of parental depression - even under control
of preexisting psychiatric disorders and other confounders. Interaction effects
and a dose-response relationship were not existent. LIMITATIONS: Class IV and V
had to be merged for the prediction analysis, a missing bias could not be ruled
out, and families with a low birth weight (between 2500 and 1500g) were not
included. CONCLUSIONS: The results are well in line with what is known from
studies so far, suggesting that maternal and paternal trajectories of depression
show distinctable patterns which are associated with a VLBW. An early screening
of mothers and fathers of a VLBW infant seems reasonable to prevent the
development of a depression in parents and further difficulties for the child.
PMID- 29331703
TI - The effects of vortioxetine on cognitive performance in working patients with
major depressive disorder: A short-term, randomized, double-blind, exploratory
study.
AB - BACKGROUND: Major Depressive Disorder (MDD) is a complex disease characterized by
emotional, physical and cognitive symptoms. We explored the efficacy of
vortioxetine versus placebo on outcomes of cognition, functioning and mood
symptoms in working patients with depression, using paroxetine as an active
reference. METHODS: Gainfully employed patients (18-65 years, N = 152) with MDD
were randomized 1:1:1 to 8 weeks' double-blind, parallel treatment either with
vortioxetine (10mg/day) or paroxetine (20mg/day), or with placebo. The primary
efficacy measure was the Digit Symbol Substitution Test (DSST), analyzed using a
mixed model for repeated measurements, and the key secondary efficacy measure was
the University of San Diego Performance-based Skills Assessment - Brief (UPSA-B),
analyzed using analysis of covariance (last observation carried forward).
RESULTS: At week 8, DSST and UPSA-B performance had improved relative to baseline
in all treatment groups, with no statistically significant differences between
treatment groups. While improvements in mood were comparable for vortioxetine and
paroxetine, numerical improvements in cognitive performance (DSST) were larger
with vortioxetine. Vortioxetine significantly improved overall cognitive
performance and clinician-rated functioning relative to placebo. The majority of
adverse events were mild or moderate, with nausea being the most common adverse
event for vortioxetine. LIMITATIONS: Small sample sizes implied limited
statistical power. CONCLUSION: This explorative study showed no significant
differences versus placebo in DSST or UPSA-B performance at week 8. However,
secondary results support vortioxetine as an effective and well-tolerated
antidepressant, supporting an added benefit for cognition and functioning, which
could have particular therapeutic relevance for the working patient population.
PMID- 29331704
TI - Mindfulness-based interventions for major depressive disorder: A comprehensive
meta-analysis of randomized controlled trials.
AB - BACKGROUND: This is a meta-analysis of randomized controlled trials (RCTs) of
mindfulness-based interventions (MBIs) for a current episode of major depressive
disorder. METHODS: Both English (PubMed, PsycINFO, Embase, and Cochrane Library
databases) and Chinese (WanFang and CNKI) databases were systematically and
independently searched. Standardized mean differences (SMDs) and risk ratio (RR)
+/- their 95% confidence intervals (CIs) based on the random effects model were
calculated. RESULTS: A total of 11 RCTs with 12 treatment arms (n = 764; MBIs =
363; and control group = 401) were identified and analyzed. Compared to the
control group, MDD subjects receiving MBIs showed significant reduction in
depressive symptoms (n =722; SMD: -0.59, 95% CI: -1.01 to -0.17, I2 = 85%, p =
0.006) at post-MBIs assessment, but the significance disappeared by the end of
posttreatment follow-up. Subgroup analyses revealed that positive benefits of
MBIs was associated with studies that had treatment as usual (TAU) control group,
Chinese participants, open label design, no gender predominance, subjects younger
than 44.4 years, and Jadad score >= 3, other illness phase and MBIs as
augmentation group. CONCLUSION: This meta-analysis found that MBIs was associated
with reduction of depression severity immediately after MBIs but not at follow up
endpoint. Further, the positive effects of MBIs were mainly driven by outlying
studies. Higher quality of RCTs with larger samples and longer study duration are
needed to confirm the findings.
PMID- 29331705
TI - Catechol O-methyltransferase (COMT) functional haplotype is associated with
recurrence of affective symptoms: A prospective birth cohort study.
AB - BACKGROUND: Catechol-O-methyltransferase (COMT) polymorphisms play an essential
role in dopamine availability in the brain. However, there has been no study
investigating whether a functional four-SNP (rs6269-rs4633-rs4818-rs4680)
haplotype is associated with affective symptoms over the life course. METHODS: We
tested this using 2093 members of the Medical Research Council National Survey of
Health and Development (MRC NSHD), who had been followed up since birth in 1946,
and had data for COMT genotypes, adolescent emotional problems (age 13-15) and at
least one measure of adult affective symptoms at ages 36, 43, 53, or 60-64 years.
First, differences in the levels of affective symptoms by the functional
haplotype using SNPs rs6269, rs4818, and rs4680 were tested in a structural
equation model framework. Second, interactions between affective symptoms by COMT
haplotype were tested under an additive model. Finally, a quadratic regressor
(haplotype2) was used in a curvilinear model, to test for a possible inverted-U
trend in affective symptoms according to COMT-related dopamine availability.
RESULTS: Women had a significant interaction between COMT haplotypes and
adolescent emotional problem on affective symptoms at age 53. Post hoc analysis
showed a significant positive association between adolescent emotional problems
and affective symptoms at age 53 years in the middle dopamine availability group
(valA/valB or met/met; beta = .11, p = .007). For men, no significant
interactions were observed. CONCLUSIONS: Combination of the COMT functional
haplotype model and inverted-U model may shed light on the effect of dopaminergic
regulation on the trajectory of affective symptoms over the life course.
PMID- 29331706
TI - The association between adherence and outcome in an Internet intervention for
depression.
AB - BACKGROUND: Adherence to Internet interventions is often reported to be rather
low and this might adversely impact the effectiveness of these interventions. We
investigated if patient characteristics are associated with adherence, and if
adherence is associated with treatment outcome in a large RCT of an Internet
intervention for depression, the EVIDENT trial. METHODS: Patients were randomized
to either care as usual (CAU) or CAU plus the Internet intervention Deprexis. A
total of 509 participants with mild to moderate depressive symptoms were included
in the intervention group and of interest for the present study. We assessed
depression symptoms pre and post intervention (12 weeks). Patient
characteristics, a self-rating screening for mental disorders, attitudes towards
online interventions, and quality of life were assessed before randomization.
RESULTS: Adherence in this study was good with on average seven hours of usage
time and eight number of sessions spent with the intervention. Some of the
patient characteristics (age, sex, depressive symptoms, and confidence in the
effectiveness of the program) predicted higher number of sessions in different
models (explaining in total between 15 and 25% of variance). Older age (beta =
.16) and higher depressive symptoms (beta = .15) were associated with higher
usage duration. Higher adherence to the program predicted a greater symptom
reduction in depressive symptoms over 12 weeks (number of sessions: beta = .13,
usage duration: beta = .14), however, this prediction could mostly be explained
by receiving guidance (beta = .27 and .26). LIMITATIONS: Receiving guidance and
symptom severity at baseline were confounded since only participants with a
moderate symptom severity at baseline received e-mail support. Therefore no firm
conclusions can be drawn from the association we observed between baseline
symptom severity and usage intensity. CONCLUSIONS: We conclude that older age was
associated with adherence and adherence was positively associated with outcome.
The effects we have found were small however suggesting that adherence might also
be influenced by further variables.
PMID- 29331707
TI - The mediation effect of PTSD, perceived job stress and resilience on the
relationship between trauma exposure and the development of depression and
alcohol use problems in Korean firefighters: A cross-sectional study.
AB - BACKGROUND: Firefighters constitute a high-risk group for depression and alcohol
use disorders (AUDs) due to frequent exposure to trauma. Perceived job stress and
resilience are powerful factors affecting the occurrence of depression and AUDs;
however, research on this subject is scarce. METHODS: We investigated the
relationship of perceived job stress and resilience with depression or AUDs in
firefighters. A total of 7151 Korean firefighters were included for analysis.
Participants completed self-report scales, including a self-reported number of
exposure to incident stressors, the Korean Occupational Stress Scale - Short
Form, the Post-traumatic Stress Disorder (PTSD) Symptoms Checklist - Civilian
version, the Patient Health Questionnaire 9, the Brief Resilience Scale, and the
Alcohol Use Disorders Identification Test. Hierarchical multivariable linear
regression analyses were performed to identify the relationship of perceived job
stress and resilience with depression or AUDs. Path analyses were applied to
investigate the mediation effects of PTSD, perceived job stress and resilience
between trauma exposure and depression or AUDs. RESULTS: There were significant
associations of perceived job stress and resilience with depression and AUDs,
respectively, even after adjusting for demographic factors, number of traumatic
events, and PTSD symptoms. The relationship between trauma exposure and
depression/AUDs was mediated by PTSD symptoms, which had both direct and indirect
effects on depression and AUDs; indirect effect was mediated by job stress and
resilience. CONCLUSIONS: The findings in this study demonstrated that PTSD,
perceived job stress and resilience can mediate the development of depression or
AUDs following trauma exposure in firefighters. Efforts to prevent PTSD, reduce
job stress and increase individual resilience could help prevent depression and
AUDs. LIMITATIONS: The cross-sectional study design and self-report nature of the
assessment tools limit the current findings.
PMID- 29331708
TI - Depression increases subjective stigma of chronic pain.
AB - BACKGROUND: Individuals suffering from mental as well as physical conditions
often face stigma, which can adversely affect functioning, treatment seeking, and
emotional health. We compared levels of stigma experienced by individuals with
depression and/or chronic pain, to contrast the perception of stigma experienced
by the sufferers with that of individuals who have never experienced these
conditions, and to determine whether depression is related to greater experience
of stigma for chronic pain. METHODS: Four groups of participants (N=236) took
part in the study: depression only, chronic pain only, comorbid depression and
chronic pain, and healthy controls. Participants underwent a clinical interview
and completed a stigma measure that assessed general self-stigma, public stigma,
treatment stigma, secrecy, and stigmatizing experiences. RESULTS: Healthy
controls largely underestimated the stigma experienced by individuals with
depression, but were not inaccurate in estimating stigma experienced by
individuals with chronic pain. Further, individuals with chronic pain alone
generally perceived less stigma for their condition than did those with
depression alone. However, comorbid individuals perceived worse stigma of chronic
pain compared to individuals with chronic pain alone, suggesting that depression
may affect the stigma felt by sufferers of conditions other than depression.
LIMITATIONS: Social desirability may have influenced stigma scores. Comparing
several groups required adapting a standardized instrument. CONCLUSIONS: Results
suggest that depression may play a role in the social experience of having a
health condition, as well as indicate that the general public continues to fail
to appreciate the negative social pressures experienced by individuals with
mental health conditions.
PMID- 29331709
TI - What do the genetic association data say about the high risk of suicide in people
with depression? A novel network-based approach to find common molecular basis
for depression and suicidal behavior and related therapeutic targets.
AB - BACKGROUND: Available sources indicate that the risk of suicide in people with
major depression is higher than other psychiatric disorders. Although it seems
that these two conditions may have a shared cause in some cases, no studies have
been conducted to identify a common basis for them. METHODS: In this study,
following an extensive review of literature, we found almost all the genes that
are involved in major depression and suicidal behavior, and we isolated genes
shared between the two conditions. Then, we found all physical or functional
interactions within three mentioned gene sets and reconstructed three genetic
interactive networks. All networks were analyzed topologically and enriched
functionally. Finally, using a drug repurposing approach, we found the main
available drugs that interacted with the most central genes shared between
suicidal behavior and depression. RESULTS: The results demonstrated that BDNF,
SLC6A4, CREB1, and TNF are the most fundamental shared genes; and generally,
disordered dopaminergic, serotonergic, and immunologic pathways in neuronal
projections are the main shared deficient pathways. In addition, we found two
genes, SLC6A4 and SLC6A2, to be the main therapeutic targets, and Serotonin
Norepinephrine Reuptake Inhibitors (SNRI) and Tricyclic Antidepressants (TCA) to
be the most effective drugs for individuals with depression at risk for suicide.
CONCLUSIONS: Our results, in addition to shedding light on the integrated
molecular basis of depression-suicide, offer new therapeutic targets for
individuals with depression at high risk for suicide and could pave the way for
future preclinical and clinical studies. However, integrative systems biology
based studies highly depend on existing data and related databases, as well as
the arrival of new experimental data sources in the future, possibly affecting
the current results.
PMID- 29331710
TI - Maternal depression and suicide at immediate prenatal and early postpartum
periods and psychosocial risk factors.
AB - Maternal depression has been intensively explored; however, less attention has
been paid to maternal suicide. No studies to date have observed maternal
depression and suicide at immediate prenatal and early postpartum stages. In
total, 213 Chinese women were recruited in hospitals after they were admitted for
childbirth. All completed a short-term longitudinal survey at perinatal stages.
Women reported lower depression scores (6.65) and higher suicidal ideation
incidence (11.74%) after childbirth. Prenatal depression raised the possibility
of prenatal suicidal ideation, while prenatal depression and suicidal ideation
increased postpartum depression and suicidal ideation. At immediate prenatal
stage, marital satisfaction protected women from depression, while miscarriage
experiences and self-esteem increased the risk. At early postpartum stage, in
contrast, being first-time mother, marital satisfaction, and harmony with mother
in-law prevented them from depression. Our study is among the first to confirm
that women have decreased depression but increased suicidal ideation at early
postpartum, and a causal relationship between them, which are worthy of public
attention. Potential protective (marital satisfaction, being first-time mother,
and harmony with mother-in-law) or risk factors (miscarriage experiences and self
esteem) of maternal depression and suicidal ideation are identified at perinatal
stages. This offers reliable guidance for clinical practice of health care.
PMID- 29331711
TI - Omega-3 supplements reduce self-reported physical aggression in healthy adults.
AB - There is emerging evidence that Omega-3 polyunsaturated fatty acids (PUFA)
supplements can decrease aggression. However, experimental studies with adults
from non-specific populations are scarce. We hypothesized that Omega-3
supplements would decrease self-reported aggression among non-clinical
participants. In a double-blind randomized trial, two groups of participants (N =
194) aged 18-45 from the general population followed a 6-weeks treatment with
638mg docosahexaenoic acid (DHA) and 772mg eicosapentaenoic acid (EPA) per day or
the equivalent quantity of copra oil (placebo). Self-reported aggressiveness was
measured at baseline and after the 6-week treatment period. Findings showed that
Omega-3 supplements significantly decreased self-reported aggressiveness at the
end of the 6-week period (d = 0.31). In conclusion, this experiment indicates
that Omega-3 administration has beneficial effects in reducing aggression among
the general population.
PMID- 29331712
TI - Genetic biomarkers for differential diagnosis of major depressive disorder and
bipolar disorder: A systematic and critical review.
AB - Depressive symptoms are present in the depressive mood state of bipolar disorder
(BPD) and major depression disorder (MDD). Often, in clinical practice, BPD
patients are misdiagnosed with MDD. Therefore, genetic biomarkers could
contribute to the improvement of differential diagnosis between BPD and MDD. This
systematic and critical review aimed to find in literature reliable genetic
biomarkers that may show differences between BPD and MDD. This systematic review
followed the PRISMA-P method. The terms used to search PubMed, Scopus, PsycINFO,
and Web of Science were depress*, bipolar, diagnos*, genetic*, biomark*. After
applying the selection criteria, N = 27 studies were selected, being n = 9 about
biomarkers for BPD; n = 15, about MDD; and n = 3 for distinguishing MDD from BPD.
A total of N = 3086 subjects were assessed in the selected studies (n = 486 in
BPD group; n = 1212 in MDD group; and n = 1388, healthy control group). The
articles were dated up to June 2017. Of the N = 27 studies, n = 16 assessed gene,
n = 1 miRNA, n = 2 lcnRNA and n = 3 protein expressions, n = 4 methylation, and n
= 4 polymorphisms. Some studies applied more than one of these genetic analyses.
To find reliable genetic biomarkers we have taken into account the methodological
care during the studies development and their validity. The genetic biomarkers
selected are related to genes that play a fundamental role in synaptic
plasticity, neurogenesis, mood control, brain ageing, immune-inflammatory
processes and mitochondrial respiratory chain. BDNF gene expression was one of
the genetic biomarkers that highlighted because of its capacity of distinguishing
BPD and MDD groups, and being adequately reproduced by more than one selected
study.
PMID- 29331713
TI - Repeated attempted homicide by administration of drugs documented by hair
analysis.
AB - Attempted murder by repeated poisoning is quite rare. The authors describe the
case of a 62-year-old man who was admitted to an intensive care unit (ICU) for
neurological disturbances complicated by inhalation pneumopathy. He presented a
loss of consciousness while his wife was visiting him at the ICU (H0). Forty
eight hours later (H48), police officers apprehended the patient's wife pouring a
liquid into his fruit salad at the hospital. Toxicological analyses of a blood
sample and the infusion equipment (H0), as well as the fruit salad and its
container (H48), confirmed the attempted poisoning with cyamemazine (H0) and
hydrochloric acid (H48). In order to evaluate the anteriority of poisonings, hair
analysis was requested and the medical records of the 6 previous months were also
examined. Two 6-cm brown hair strands were sampled and the victim's medical
record was seized in order to determine the treatments he had been given during
the previous six months. Segmental hair testing on two 6-cm brown hair was
conducted by GC-MS, LC-DAD and LC-MS/MS (0-2/2-4/4-6 cm; pg/mg). Haloperidol
(9200/1391/227), amitriptyline (7450/1850/3260), venlafaxine (332/560/260), that
had never been part of the victim's treatment were detected, as well as some
benzodiazepines (alprazolam, bromazepam, nordazepam); cyamemazine was also
detected in all the segments (9960/1610/2367) though only a single dose
administration was reported in the medical records. The toxicological analyses
performed at H0 and H48 confirmed the homicide attempts in the ICU. In addition,
comparison of the results in hair analysis with the medical records confirmed
repeated poisoning attempts over the previous six months, and thus explain the
origin of the disorders presented by the victim. This case serves to remind us
that repeated attempted murder can be difficult to diagnose and that hair
analysis can be an effective way to detect such attempts.
PMID- 29331714
TI - Stature estimation formulae for Mexican contemporary population: A sample based
study of long bones.
AB - Stature estimation is an important step to create a biological profile for human
identification of unknown individuals in forensic anthropological practice, and
it is well known that the long bone length is highly correlated with this
feature. The purpose of the present study is to develop formulae for height
estimation, based on simple linear regression model for humerus, femur and tibia
in Mexican contemporary population. Stature was taken in 56 males and 30 female
corpses as well as maximum length of three long bones of the limbs after autopsy
following the Menendez et al. (2014) criteria, at the Facultad de Medicina
(School of Medicine) of the Universidad Nacional Autonoma de Mexico. Based on
this data, equations for each sex and for the three long bones were developed,
obtaining a highly significant (p < .001) linear regression models with
correlation coefficients of r = 0.820 for female femur and r = 0.855 for male
tibia. In this manner, the new formulae provide better and reliable results of
stature estimation for the contemporary population of Mexico.
PMID- 29331715
TI - Toxicokinetics of Zn and Cd in the earthworm Eisenia andrei exposed to metal
contaminated soils under different combinations of air temperature and soil
moisture content.
AB - This study evaluated how different combinations of air temperature (20 degrees C
and 25 degrees C) and soil moisture content (50% and 30% of the soil water
holding capacity, WHC), reflecting realistic climate change scenarios, affect the
bioaccumulation kinetics of Zn and Cd in the earthworm Eisenia andrei. Earthworms
were exposed for 21 d to two metal-contaminated soils (uptake phase), followed by
21 d incubation in non-contaminated soil (elimination phase). Body Zn and Cd
concentrations were checked in time and metal uptake (k1) and elimination (k2)
rate constants determined; metal bioaccumulation factor (BAF) was calculated as
k1/k2. Earthworms showed extremely fast uptake and elimination of Zn, regardless
of the exposure level. Climate conditions had no major impacts on the
bioaccumulation kinetics of Zn, although a tendency towards lower k1 and k2
values was observed at 25 degrees C + 30% WHC. Earthworm Cd concentrations
gradually increased with time upon exposure to metal-contaminated soils,
especially at 50% WHC, and remained constant or slowly decreased following
transfer to non-contaminated soil. Different combinations of air temperature and
soil moisture content changed the bioaccumulation kinetics of Cd, leading to
higher k1 and k2 values for earthworms incubated at 25 degrees C + 50% WHC and
slower Cd kinetics at 25 degrees C + 30% WHC. This resulted in greater BAFs for
Cd at warmer and drier environments which could imply higher toxicity risks but
also of transfer of Cd within the food chain under the current global warming
perspective.
PMID- 29331716
TI - Bioremediation of cadmium- and zinc-contaminated soil using Rhodobacter
sphaeroides.
AB - Bioremediation using microorganisms is a promising technique to remediate soil
contaminated with heavy metals. In this study, Rhodobacter sphaeroides was used
to bioremediate soils contaminated with cadmium (Cd) and zinc (Zn). The study
found that the treatment reduced the overall bioavailable fractions (e.g.,
exchangeable and carbonate bound phases) of Cd and Zn. More stable fractions
(e.g., Fe-Mn oxide, organic bound, and residual phases (only for Zn)) increased
after bioremediation. A wheat seedling experiment revealed that the
phytoavailability of Cd was reduced after bioremediation using R. sphaeroides.
After bioremediation, the exchangeable phases of Cd and Zn in soil were reduced
by as much as 30.7% and 100.0%, respectively; the Cd levels in wheat leaf and
root were reduced by as much as 62.3% and 47.2%, respectively. However, when the
soils were contaminated with very high levels of Cd and Zn (Cd 54.97-65.33 mg kg
1; Zn 813.4-964.8 mg kg-1), bioremediation effects were not clear. The study also
found that R. sphaeroides bioremediation in soil can enhance the Zn/Cd ratio in
the harvested wheat leaf and root overall. This indicates potentially favorable
application in agronomic practice and biofortification. Although remediation
efficiency in highly contaminated soil was not significant, R. sphaeroides may be
potentially and practically applied to the bioremediation of soils co
contaminated by Cd and Zn.
PMID- 29331717
TI - In vitro dermal bioaccessibility of selected metals in contaminated soil and mine
tailings and human health risk characterization.
AB - Dermal exposure to contaminated sites has generally received less attention than
oral/inhalation exposure due to limited exposure scenarios and less perceived
potential for toxicity, however, the risk can be significant for specific
contaminants and scenarios. The present study aims to (1) measure Cr, Ni, Pb, and
Zn contamination in soil and mine tailings samples (n = 7), (2) determine the
dermal bioaccessibility of these metals via in vitro tests using two synthetic
sweat formulations (EN 1811; NIHS 96-10), and (3) obtain dermal absorbed doses
(DADs) for children's and adults' exposure scenarios and compare them to derived
dermal reference values. The NIHS 96-10 formulation yielded higher
bioaccessibility values for all metals than EN 1811, possibly due to its lower
pH. Zn had the highest bioaccessibility for both formulations whereas Cr had the
lowest. There was some evidence of adsorption of initially mobilized Pb and Zn to
soil with longer test times, resulting in slightly lower bioaccessibility after 8
h of testing with respect to 2 h. The calculated DADs showed that the risk for
exposure was acceptable (DAD < derived dermal reference value) for all metals
except for Cr(VI) considering exposure to two of the samples. The risk in the
case of children's exposure scenario (play on contaminated medium) was
significantly higher than the case for the adults' exposure scenario (exposure in
industrial context). Additional bioaccessibility research is recommended on
additional samples with differing properties/contamination profiles, on
additional contaminants with high dermal affinity (especially As), and on the
development/validation of in vitro dermal bioaccessibility tests.
PMID- 29331718
TI - Partition of Zn, Cd, and Pb during co-combustion of sedum plumbizincicola and
sewage sludge.
AB - Co-combustion of sedum plumbizincicola and sewage sludge was performed in a
tubular furnace. The influence of experimental conditions on the partitioning of
Zn, Cd, and Pb was investigated. The results showed that 30% sewage sludge was
proposed as the optimal ratio for the co-combustion as a compromise between low
calorific value and high amount of heavy metal remained in the bottom ash. High
temperature increased the volatilization degree of heavy metals, among which the
performance of Cd and Pb was obvious than Zn. Rising oxygen concentration was
beneficial to the formation of heavy metal compounds, and the effect of oxygen on
Zn was the most pronounced. Thermodynamic equilibrium calculation was carried out
to forecast heavy metal compounds. The results demonstrated that Zn, Cd, and Pb
mainly generated ZnAl2O4, CdSiO3 and PbSiO3 in solid phase, which are partly
confirmed by X-ray diffraction (XRD). The promising results offered a great
possibility of heavy metal immobilization, indicating the combustion of Sedum
plumbizincicola with sewage sludge is an effective way for waste disposal.
PMID- 29331719
TI - Regulated effects of Prorocentrum donghaiense Lu exudate on nickel
bioavailability when cultured with different nitrogen sources.
AB - Exudates by marine phytoplankton and metals coexist in the seawater, but little
is known about their interaction. In this study, cultures of Prorocentrum
donghaiense Lu were grown in urea and ammonium, and then exposed to different Ni
ion levels in order to study the effects of Ni ions on algal growth. The
regulatory mechanisms of P. donghaiense Lu for coping with different Ni ion
levels was investigating by characterizing dissolved organic carbon (DOC),
carbohydrate and protein content released per cell, hydropathy properties
(hydrophilic and hydrophobic fractions) and thiol compounds (cysteine-like or
glutathione-like). Lower levels of Ni ions (pNi>10.0) significantly promoted the
growth of P. donghaiense Lu when incubated in urea; however, the same was not
true for P. donghaiense Lu cultivated in ammonium. An increased presence of
hydrophobic fractions and thiol compounds (cysteine-like or glutathione-like
compounds) induced by low Ni ions (pNi>10.0) in urea cultures suggest that the
activation of cellular mechanisms in response to insufficient Ni ion stress
enhances Ni bioavailability. Furthermore, the abundance of carbohydrates and
proteins released by cells when exposed to higher Ni ions levels (from pNi = 10.0
to pNi = 8.0) both in urea and ammonium cultures suggests that algal cells may
utilize exudate to complex Ni cations and reduce their toxicity. Therefore, it
can be speculated that phytoplankton can produce large amounts of specific
exudate, which may accelerate the metal bioavailability (insufficient levels) and
reduce metal toxicity (excess levels) to maintain an equilibrium with metals in
the environment.
PMID- 29331720
TI - Temporal-spatial gait parameter models of very slow walking.
AB - This study assessed the relationship between walking speed and common temporal
spatial stride-parameters to determine if a change in gait strategy occurs at
extremely slow walking speeds. Stride-parameter models that represent slow
walking can act as a reference for lower extremity exoskeleton and powered
orthosis controls since these devices typically operate at walking speeds less
than 0.4 m/s. Full-body motion capture data were collected from 30 health adults
while walking on a self-paced treadmill, within a CAREN-Extended virtual reality
environment. Kinematic data were collected for 0.2-0.8 m/s, and self-selected
walking speed. Eight temporal stride-parameters were determined and their
relationship to walking speed was assessed using linear and quadratic regression.
Stride-length, step-length, and step-frequency were linearly related to walking
speed, even at speeds below 0.4 m/s. An inflection point at 0.5 m/s was found for
stride-time, step-time, stance-time, and double support time. Equations were
defined for each stride-parameter, with equation outputs producing correlations
greater than 0.91 with the test data. This inflection point suggests a change in
gait strategy at very slow walking speeds favouring greater ground contact time.
PMID- 29331721
TI - Understanding protein-drug interactions using ion mobility-mass spectrometry.
AB - Ion mobility-mass spectrometry (IM-MS) is an important addition to the analytical
toolbox for the structural evaluation of proteins, and is enhancing many areas of
biophysical analysis. Disease-associated proteins, including enzymes such as
protein kinases, transcription factors exemplified by p53, and intrinsically
disordered proteins, including those prone to aggregation, are all amenable to
structural analysis by IM-MS. In this review we discuss how this powerful
technique can be used to understand protein conformational dynamics and
aggregation pathways, and in particular, the effect that small molecules,
including clinically-relevant drugs, play in these processes. We also present
examples of how IM-MS can be used as a relatively rapid screening strategy to
evaluate the mechanisms and conformation-driven aspects of protein:ligand
interactions.
PMID- 29331722
TI - Effect of vitamin D supplementation on serum sclerostin levels in chronic kidney
disease.
AB - Vitamin D deficiency, cardiovascular disease and abnormal bone mineral metabolism
are common in chronic kidney disease (CKD). Abnormal bone mineral metabolism has
been linked to vascular calcification in CKD. Sclerostin has emerged as an
important messenger in cross talk between bone-vascular axis. We analyzed
sclerostin in subjects who participated in the randomized, double blind, placebo
controlled trial investigating the effect of cholecalciferol supplementation on
vascular function in non-diabetic CKD stage G3-4 and vitamin D <= 20 ng/ml
[CTRI/2013/05/003648]. Patients were randomized (1:1) to receive either two
directly observed oral doses of 300,000 IU of cholecalciferol or matching placebo
at baseline and 8 weeks. Of the 120 subjects enrolled, 58 in the cholecalciferol
group and 59 in the placebo group completed the study. At baseline, serum levels
of sclerostin were similar in both groups (cholecalciferol - median;190pg/ml,
IQR;140-260 pg/ml and placebo - median;180 pg/ml, IQR; 140-240 pg/ml, p = 0.67).
16 weeks after cholecalciferol supplementation, there was no change in level of
sclerostin (mean change;1.10 pg/ml, 95%CI; -27.34 to 29.34 pg/ml, p = 0.25).
However, a significant decrease in sclerostin level was noted in the placebo
group (mean change; -31.94 pg/ml, 95%CI; -54.76 to -9.13 pg/ml, p = 0.002).
Change (Delta) in sclerostin level at 16 weeks correlated negatively with Delta
eGFR (r = -0.20, p = 0.03) and positively with Deltauric acid (r = 0.37, p <
0.001) but not with Delta25(OH) D (r = 0.06, p = 0.54), Delta iPTH (r = - 0.03, p
= 0.78) DeltaFGF23 (r = - 0.08, p = 0.38) and Delta125 (OH)2 D (r = - 0.04, p =
0.65). In conclusion, high dose cholecalciferol supplementation did not change
sclerostin levels in non-diabetic stage 3-4 CKD subjects.
PMID- 29331723
TI - Progesterone arrested cell cycle progression through progesterone receptor
isoform A in pancreatic neuroendocrine neoplasm.
AB - In pancreatic neuroendocrine neoplasms (Pan-NEN) progesterone signaling has been
shown to have both inhibitory and stimulatory effects on cell proliferation. The
ability of progesterone to inhibit tumor proliferation is of particular interest
and is suggested to be mediated through the less abundantly expressed
progesterone receptor (PR) isoform A (PRA). To date the mechanistic processes
underlying this inhibition of proliferation remain unclear. To examine the
mechanism of PRA actions, the human Pan-NEN cell line QGP-1, that endogenously
expresses PR isoform B (PRB) without PRA, was transfected with PRA. PRA
transfection suppressed the majority of cell cycle related genes increased by
progesterone including cyclin A2 (CCNA2), cyclin B1 (CCNB1), cyclin-dependent
kinase 1 (CDK1) and cyclin-dependent kinase 2 (CDK2). Importantly, following
progesterone administration cell cycle distribution was shifted to S and G2/M
phases in the naive cell line but in PRA-transfected cells, this effect was
suppressed. To see if these mechanistic insights were confirmed in patient
samples PRA, PRB, CCNA2, CCNB, CDK1 and CDK2 immunoreactivities were assessed in
Pan-NEN cases. Higher levels of cell cycle markers were associated with higher
WHO grade tumors and correlations between the markers suggested formation of
cyclin/CDK activated complexes in S and G2/M phases. PRA expression was
associated with inverse correlation of all cell cycle markers. Collectively,
these results indicate that progesterone signals through PRA negatively regulates
cell cycle progression through suppressing S and G2/M phases and downregulation
of cell cycle phases specific cyclins/CDKs.
PMID- 29331724
TI - Diminution of arsenic accumulation in rice seedlings co-cultured with Anabaena
sp.: Modulation in the expression of lower silicon transporters, two nitrogen
dependent genes and lowering of antioxidants activity.
AB - The present study was intended to investigate the role of algae, Anabaena sp. in
the amelioration of As toxicity, when co-cultured with rice seedlings. The
reduction of growth in rice seedlings against As(III) and As(V) was recovered
with Anabaena sp. The Anabaena sp. also reduced the accumulation of As, where it
was more efficient against 60uM As(III) (49%) than As(V) (23%) in rice shoot.
Similarly, with reduction of As accumulation, lower silicon transporters (Lsi-1
and Lsi-2) was found to be suppressed against As treatments. However, the
expression of two nitrogen dependent genes i.e., NR and SAMT were found to be
enhanced with the Anabaena sp. Likewise, the activity of antioxidant enzyme, GST,
was enhanced, whereas, the activity of other enzymes such as SOD, APX, GPX, GR
and DHAR were decreased with As+Algae combinations. Overall, the result suggested
that the Anabaena sp. reduces As accumulation, modulates gene expressions and
antioxidants to ameliorate the As toxicity in Oryza sativa L.
PMID- 29331725
TI - BiVO4 /N-rGO nano composites as highly efficient visible active photocatalyst for
the degradation of dyes and antibiotics in eco system.
AB - Herein, we report the synthesis of novel nitrogen doped reduced graphene oxide/
BiVO4 photo catalyst by single step hydrothermal method. The physicochemical
properties of the catalysts were characterized using XRD, N2 adsorption
desorption, Raman, XPS, SEM TEM, DRS-UV and EIS techniques. The synthesized
catalysts were tested for their catalytic activity in the photo degradation of
some harmful textile dyes (methylene blue & congo red) and antibiotics
(metronidazole and chloramphenicol) under visible light irradiation. Reduced
charge recombination and enhanced photocatalytic activity were observed due to
the concerted effect between BiVO4 and nitrogen-rGO. The degradation efficiency
of BiVO4/N-rGO in the degradation of CR and MB was remarkably high i.e 95% and
98% under visible light irradiation. Similarly 95% of MTZ and 93% of CAP were
degraded under visible light irradiation. HPLC studies implied that both the dyes
and antibiotics were degraded to the maximum extent. The plausible photocatalytic
mechanism on the basis of experimental results was suggested.
PMID- 29331726
TI - Impact of the start-up process on the microbial communities in biocathodes for
electrosynthesis.
AB - This study seeks to understand how the bacterial communities that develop on
biocathodes are influenced by inocula diversity and electrode potential during
start-up. Two different inocula are used: one from a highly diverse environment
(river mud) and the other from a low diverse milieu (anaerobic digestion). In
addition, both inocula were subjected to two different polarising voltages:
oxidative (+0.2 V vs. Ag/AgCl) and reductive (-0.8 V vs. Ag/AgCl). Bacterial
communities were analysed by means of high throughput sequencing. Possible
syntrophic interactions and competitions between archaea and eubacteria were
described together with a discussion of their potential role in product formation
and current production. The results confirmed that reductive potentials lead to
an inconsistent start-up procedure regardless of the inoculum used. However,
imposing oxidative potentials help to quickly develop an electroactive biofilm
ready to withstand reductive potentials (i.e. biocathodic operation). The
microbial structure that finally developed on them was highly dependent on the
raw community present in the inoculum. Using a non-specialised inoculum resulted
in a highly specialised biofilm, which was accompanied by an improved performance
in terms of consumed current and product generation. Interestingly, a much more
specialised inoculum promoted a rediversification in the biofilm, with a lower
general cell performance.
PMID- 29331728
TI - The effect of bioadhesive on the interfacial compatibility and pervaporation
performance of composite membranes by MD and GCMC simulation.
AB - Combing molecular dynamics (MD) and Grand Canonical Monte Carlo (GCMC)
simulation, the effect of bioadhesive transition layer on the interfacial
compatibility of the pervaporation composite membranes, and the pervaporation
performance toward penetrant molecules were investigated. In our previous
experimental study, the structural stability and permeability selectivity of the
composite membranes were considerably enhanced by the introduction of bioadhesive
carbopol (CP). In the present study, the interfacial compatibility and the
interfacial energies between the chitosan (CS) separation layer, CP transition
layer and the support layer were investigated, respectively. The mobility of
polymer chains, free volume in bulk and interface regions were evaluated by the
mean-square displacement (MSD) and free volume voids (FFV) analysis. The
diffusion and sorption behavior of water/ethanol molecules in bulk and interface
regions were characterized. The simulation results of membrane structure have
good consistency, indicating that the introduction of CP transition layer
improved the interfacial compatibility and interaction between the separation
layer and the support layer. Comparing the bulk region of the separation layer,
the mobility and free volume of the polymer chain in the interface region
decreased and thus reduced the swelling of CS active layer, revealing the
increased diffusion selectivity toward the permeated water and ethanol molecules.
The strong hydrogen bonds interaction between the COOH of the CP transition layer
and water molecules increased the adsorption of water molecules in the interface
region. The simulation results were quite consistent with the experimental
results.
PMID- 29331729
TI - Strong CH/O interactions between polycyclic aromatic hydrocarbons and water:
Influence of aromatic system size.
AB - Energies of CH/O interactions between water molecule and polycyclic aromatic
hydrocarbons with a different number of aromatic rings were calculated using ab
initio calculations at MP2/cc-PVTZ level. Results show that an additional
aromatic ring in structure of polycyclic aromatic hydrocarbons significantly
strengthens CH/O interactions. Calculated interaction energies in optimized
structures of the most stable tetracene/water complex is -2.27 kcal/mol,
anthracene/water is -2.13 kcal/mol and naphthalene/water is -1.97 kcal/mol. These
interactions are stronger than CH/O contacts in benzene/water complex (-1.44
kcal/mol) while CH/O contacts in tetracene/water complex are even stronger than
CH/O contacts in pyridine/water complexes (-2.21 kcal/mol). Electrostatic
potential maps for different polycyclic aromatic hydrocarbons were calculated and
used to explain trends in the energies of interactions.
PMID- 29331727
TI - Individual variation in working memory is associated with fear extinction
performance.
AB - PTSD has been associated consistently with abnormalities in fear acquisition and
extinction learning and retention. Fear acquisition refers to learning to
discriminate between threat and safety cues. Extinction learning reflects the
formation of a new inhibitory-memory that competes with a previously learned
threat-related memory. Adjudicating the competition between threat memory and the
new inhibitory memory during extinction may rely, in part, on cognitive processes
such as working memory (WM). Despite significant shared neural circuits and
signaling pathways the relationship between WM, fear acquisition, and extinction
is poorly understood. Here, we analyzed data from a large sample of healthy
Marines who underwent an assessment battery including tests of fear acquisition,
extinction learning, and WM (N-back). Fear potentiated startle (FPS), fear
expectancy ratings, and self-reported anxiety served as the primary dependent
variables. High WM ability (N = 192) was associated with greater CS + fear
inhibition during the late block of extinction and greater US expectancy change
during extinction learning compared to individuals with low WM ability (N = 204).
WM ability was not associated with magnitude of fear conditioning/expression.
Attention ability was unrelated to fear acquisition or extinction supporting
specificity of WM associations with extinction. These results support the
conclusion that individual differences in WM may contribute to regulating fear
responses.
PMID- 29331730
TI - Exenatide exerts cognitive effects by modulating the BDNF-TrkB neurotrophic axis
in adult mice.
AB - Modulation of insulin-dependent signaling is emerging as a valuable therapeutic
tool to target neurodegeneration. In the brain, the activation of insulin
receptors promotes cell growth, neuronal repair, and protection. Altered brain
insulin signaling participates in the cognitive decline seen in Alzheimer's
disease patients and the aging brain. Glucagon-like peptide-1 (GLP-1) regulates
insulin secretion and, along with GLP-1 analogues, enhances neurotrophic
signaling and counteracts cognitive deficits in preclinical models of
neurodegeneration. Moreover, recent evidence indicates that GLP-1 modulates the
activity of the brain-derived neurotrophic factor (BDNF). In this study, in adult
wild-type mice, here employed as a model of mid-life brain aging, we evaluated
the effects of a 2-month treatment with exenatide, a GLP-1 analogue. We found
that exenatide promotes the enhancement of long-term memory performances.
Biochemical and imaging analyses show that the drug promotes the activation of
the BDNF-TrkB neurotrophic axis and inhibits apoptosis by decreasing p75NTR
mediated signaling. The study provides preclinical evidence for the use of
exenatide to delay age-dependent cognitive decline.
PMID- 29331731
TI - Deoxynivalenol, gut microbiota and immunotoxicity: A potential approach?
AB - Deoxynivalenol (DON, vomitoxin) is the most frequent mycotoxin in grains and
grain products. DON contamination in fodder and food is a serious threat for
health, since it impairs the immune and gastrointestinal systems of both human
and animals. Gut microbiota seems to play a more and more important part in human
and animals' health according to related researches. Previous studies implied
some associations among gut microbiota, DON and immune system. For example, DON
affects immune system as well as the composition and abundance of gut microbiota,
and the latter influences immune system as well. In the present short review, we
not only provide the available information about the toxic consequences of DON
induced immunotoxicity on different animals and cell lines and discuss its main
possible molecule mechanisms, but also summarize research results concerning the
role of gut microbiota in DON-induced immunotoxicity and gender differences, with
the aim to find some potential therapeutic strategies to tackle DON-induced
immunotoxicity.
PMID- 29331732
TI - Computational toxicology: From cheminformatics to nanoinformatics.
PMID- 29331733
TI - Aronia melanocarpa fruit juice ameliorates the symptoms of inflammatory bowel
disease in TNBS-induced colitis in rats.
AB - Trinitrobenzensulfonic acid (TNBS) is commonly used to induce an experimental
inflammatory bowel disease (IBD) model. Oxidative stress and inflammation have
been proposed as mechanisms underlying the pathophysiology of IBD. Aronia
melanocarpa fruit juice (AMFJ) is extremely rich in polyphenolic substances,
mainly proanthocyanidins, flavonoids and phenolic acids. The aim of this study
was to evaluate the effect of AMFJ in a rat TNBSinduced colitis model and to
compare the effect of the juice with that of sulfasalazine. Colitis was induced
by TNBS in male Wistar rats. After the induction of colitis, AMFJ at three doses
(2.5, 5 and 10 mL/kg) and sulfasalazine (400 mg/kg) were administered orally till
the 14th experimental day. Severity of colitis was assessed by macroscopic and
histopathological criteria. Oxidative stress was evaluated by the concentration
of thiobarbituric acid reactive substances (TBARS). TNBS caused severe colonic
damage. AMFJ dose-dependently ameliorated TNBS-induced colitis. It improved the
macroscopic and microscopic signs of colitis, and prevented the increase of
colonic TBARS concentrations. Regarding different indices, the effect of AMFJ was
comparable or even higher than that of sulfasalazine. In conclusion, the
ameliorative effects of AMFJ in the experimental TNBSinduced colitis might be the
result of its potent antioxidant and antiinflammatory properties.
PMID- 29331734
TI - In vitro assessment of silver nanoparticles immunotoxicity.
AB - This study aimed to characterize unwanted immune effects of nanoparticles (NP)
using THP-1 cells, human whole blood and enriched peripheral blood monocytes.
Commercially available silver NP (AgNP < 100 nm, also confirmed by Single
Particle Extinction and Scattering) were used as prototypical NP. Cells were
treated with AgNP alone or in combination with classical immune stimuli (i.e.
LPS, PHA, PWM) and cytokine assessed; in addition, CD54 and CD86 expression was
evaluated in THP-1 cells. AgNP alone induced dose-related IL-8 production in all
models, with higher response observed in THP-1 cells, possibly connected to
different protein corona formation in bovine versus human serum. AgNP potentiated
LPS-induced IL-8 and TNF-alpha, but not LPS-induced IL-10. AgNP alone induced
slight increase in IL-4, and no change in IFN-gamma production. While responses
to PHA in term of IL-4 and IFN-gamma production were not affected, increased PWM
induced IL-4 and IFN-gamma production were observed, suggesting potentiation of
humoral response. Reduction in PHA-induced IL-10 was observed. Overall, results
indicate immunostimulatory effects. THP-1 cells work as well as primary cells,
representing a useful and practical alternative, with the awareness that from a
physiological point of view the whole blood assay is the one that comes closest
to reality.
PMID- 29331735
TI - Internal exposure-based pharmacokinetic evaluation of potential for
biopersistence of 6:2 fluorotelomer alcohol (FTOH) and its metabolites.
AB - Polyfluorinated compounds (PFCs) are authorized for use as greaseproofing agents
in food contact paper. As C8-PFCs (8-carbons) are known to accumulate in tissues,
shorter-chain C6-PFCs (6-carbons) have replaced C8-PFCs in many food contact
applications. However, the potential of C6-PFCs for human biopersistence has not
been fully evaluated. For the first time, we provide internal exposure estimates
to key metabolites of 6:2 fluorotelomer alcohol (6:2 FTOH), a monomeric component
of C6-PFCs, to extend our understanding of exposure beyond estimates of external
exposure. Pharmacokinetic data from published rat and human studies on 6:2 FTOH
were used to estimate clearance and area under the curve (AUC) for its
metabolites: 5:3 fluorotelomer carboxylic acid (5:3 A), perfluorohexanoic acid
(PFHxA) and perfluoroheptanoic acid (PFHpA). Internal exposure to 5:3 A was the
highest of evaluated metabolites across species and it had the slowest clearance.
Additionally, 5:3 A clearance decreased with increasing 6:2 FTOH exposure. Our
analysis provides insight into association of increased internal 5:3 A exposure
with high biopersistence potential of 6:2 FTOH. Our results identify 5:3 A as an
important biomarker of internal 6:2 FTOH exposure for use in biomonitoring
studies, and are potentially useful for toxicological assessment of chronic
dietary 6:2 FTOH exposure.
PMID- 29331737
TI - Hematology reference intervals for neonatal Holstein calves.
AB - Data regarding hematologic reference intervals (RI) for neonatal calves have not
been published yet. The aims of this study were: a) to establish hematology RIs
for neonatal Holstein calves, b) to compare them with the RIs for lactating cows,
and c) to investigate the relationship of age and gender with the hematologic
profile of calves. Two-hundred and fifty-four clinically healthy Holstein calves
(1-9days old, from 30 farms) and 82 healthy Holstein cows (between 30 and 150days
in milk, from 10 farms) were blood sampled once for a complete blood count
evaluation, using the ADVIA 120 hematology analyzer. An additional blood sample
was collected from each calf for serum total protein concentration measurement.
RIs and age-related RIs were calculated with the Reference Value Advisor
freeware. Comparisons between calves and cows and between male and female calves
were performed with t-test or Mann-Whitney test. Red blood cell count (RBC),
white blood cell count (WBC), neutrophil, lymphocyte and platelet counts in
calves were higher, while mean corpuscular volume (MCV), mean corpuscular
hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) were lower
than in cows. Lymphocyte and platelets showed a notable increase through age.
Finally, female calves had higher RBC, hematocrit and hemoglobin concentration
than males. Age-specific RIs should be used for the interpretation of the
complete blood count in Holstein calves.
PMID- 29331738
TI - Recent advances in neural dust: towards a neural interface platform.
AB - The neural dust platform uses ultrasonic power and communication to enable a
scalable, wireless, and batteryless system for interfacing with the nervous
system. Ultrasound offers several advantages over alternative wireless
approaches, including a safe method for powering and communicating with sub mm
sized devices implanted deep in tissue. Early studies demonstrated that neural
dust motes could wirelessly transmit high-fidelity electrophysiological data in
vivo, and that theoretically, this system could be miniaturized well below the mm
scale. Future developments are focused on further minimization of the platform,
better encapsulation methods as a path towards truly chronic neural interfaces,
improved delivery mechanisms, stimulation capabilities, and finally refinements
to enable deployment of neural dust in the central nervous system.
PMID- 29331739
TI - Determination of atomic-scale chemical composition at semiconductor
heteroepitaxial interfaces by high-resolution transmission electron microscopy.
AB - The determination of atomic structures and further quantitative information such
as chemical compositions at atomic scale for semiconductor defects or
heteroepitaxial interfaces can provide direct evidence to understand their
formation, modification, and/or effects on the properties of semiconductor films.
The commonly used method, high-resolution transmission electron microscopy
(HRTEM), suffers from difficulty in acquiring images that correctly show the
crystal structure at atomic resolution, because of the limitation in microscope
resolution or deviation from the Scherzer-defocus conditions. In this study, an
image processing method, image deconvolution, was used to achieve atomic
resolution (~1.0 A) structure images of small lattice-mismatch (~1.0%) AlN/6H-SiC
(0001) and large lattice-mismatch (~8.5%) AlSb/GaAs (001) heteroepitaxial
interfaces using simulated HRTEM images of a conventional 300-kV field-emission
gun transmission electron microscope under non-Scherzer-defocus conditions. Then,
atomic-scale chemical compositions at the interface were determined for the
atomic intermixing and Lomer dislocation with an atomic step by analyzing the
deconvoluted image contrast. Furthermore, the effect of dynamical scattering on
contrast analysis was also evaluated for differently weighted atomic columns in
the compositions.
PMID- 29331736
TI - Dysfunctional telomeres and hematological disorders.
AB - Telomere biology disorders, which are characterized by telomerase activity
haploinsufficiency and accelerated telomere shortening, most commonly manifest as
degenerative diseases. Tissues with high rates of cell turnover, such as those in
the hematopoietic system, are particularly vulnerable to defects in telomere
maintenance genes that eventually culminate in bone marrow (BM) failure
syndromes, in which the BM cannot produce sufficient new blood cells. Here, we
review how telomere defects induce degenerative phenotypes across multiple
organs, with particular focus on how they impact the hematopoietic stem and
progenitor compartment and affect hematopoietic stem cell (HSC) self-renewal and
differentiation. We also discuss how both the increased risk of myelodysplastic
syndromes and other hematological malignancies that is associated with telomere
disorders and the discovery of cancer-associated somatic mutations in the
shelterin components challenge the conventional interpretation that telomere
defects are cancer-protective rather than cancer-promoting.
PMID- 29331740
TI - Development and validation of a new population-based simulation model of
osteoarthritis in New Zealand.
AB - OBJECTIVE: To describe the construction and preliminary validation of a new
population-based microsimulation model developed to analyse the health and
economic burden and cost-effectiveness of treatments for knee osteoarthritis (OA)
in New Zealand (NZ). METHOD: We developed the New Zealand Management of
Osteoarthritis (NZ-MOA) model, a discrete-time state-transition microsimulation
model of the natural history of radiographic knee OA. In this article, we report
on the model structure, derivation of input data, validation of baseline model
parameters against external data sources, and validation of model outputs by
comparison of the predicted population health loss with previous estimates.
RESULTS: The NZ-MOA model simulates both the structural progression of
radiographic knee OA and the stochastic development of multiple disease symptoms.
Input parameters were sourced from NZ population-based data where possible, and
from international sources where NZ-specific data were not available. The
predicted distributions of structural OA severity and health utility detriments
associated with OA were externally validated against other sources of evidence,
and uncertainty resulting from key input parameters was quantified. The resulting
lifetime and current population health-loss burden was consistent with estimates
of previous studies. CONCLUSION: The new NZ-MOA model provides reliable estimates
of the health loss associated with knee OA in the NZ population. The model
structure is suitable for analysis of the effects of a range of potential
treatments, and will be used in future work to evaluate the cost-effectiveness of
recommended interventions within the NZ healthcare system.
PMID- 29331742
TI - A sensitive and selective immunoaffinity column clean up coupled to UPLC-MS/MS
for determination of trace methyl-3-quinoxaline-2-carboxylic acid in animal
tissues.
AB - This paper described a reliable and simple method for the selective determination
of MQCA in animal tissues using ultra high performance liquid chromatography
tandem mass spectrometry (UHPLC-MS/MS). A highly targeted immunoaffinity column
was used for sample purification after enzymatic hydrolysis. The purified
extracts were analyzed by reversed-phase HPLC-MS/MS in positive ESI and multiple
reaction monitoring mode. The calibration curves showed good linearity with
correlation coefficient (r2) larger than 0.995. The average recoveries at the
spiked levels of 0.5, 2.0 and 20MUgkg-1 were 90.2% to 103.5% with intra-day and
inter-day relatives standard deviations (RSD, n=6) ranging from 1.8% to 6.7% and
3.5% to 7.6% respectively. The limit of quantification (LOQ) was 0.5MUgkg-1,
which can fulfil the maximum residue level (MRL) of 4.0MUgkg-1 stipulated by the
Agricultural Minister of China and the requirement of the confirmatory criteria
according to the European Commission Decision 2002/657/EC. The method is
sensitive, accurate, convenient and rapid, and has been successfully applied in
real samples.
PMID- 29331743
TI - Preliminary investigation of human exhaled breath for tuberculosis diagnosis by
multidimensional gas chromatography - Time of flight mass spectrometry and
machine learning.
AB - Tuberculosis (TB) remains a global public health malady that claims almost 1.8
million lives annually. Diagnosis of TB represents perhaps one of the most
challenging aspects of tuberculosis control. Gold standards for diagnosis of
active TB (culture and nucleic acid amplification) are sputum-dependent, however,
in up to a third of TB cases, an adequate biological sputum sample is not readily
available. The analysis of exhaled breath, as an alternative to sputum-dependent
tests, has the potential to provide a simple, fast, and non-invasive, and ready
available diagnostic service that could positively change TB detection. Human
breath has been evaluated in the setting of active tuberculosis using thermal
desorption-comprehensive two-dimensional gas chromatography-time of flight mass
spectrometry methodology. From the entire spectrum of volatile metabolites in
breath, three random forest machine learning models were applied leading to the
generation of a panel of 46 breath features. The twenty-two common features
within each random forest model used were selected as a set that could
distinguish subjects with confirmed pulmonary M. tuberculosis infection and
people with other pathologies than TB.
PMID- 29331741
TI - Extracellular acidification induces ROS- and mPTP-mediated death in HEK293 cells.
AB - The extracellular pH (pHe) is a key determinant of the cellular
(micro)environment and needs to be maintained within strict boundaries to allow
normal cell function. Here we used HEK293 cells to study the effects of pHe
acidification (24h), induced by mitochondrial inhibitors (rotenone, antimycin A)
and/or extracellular HCl addition. Lowering pHe from 7.2 to 5.8 reduced cell
viability by 70% and was paralleled by a decrease in cytosolic pH (pHc),
hyperpolarization of the mitochondrial membrane potential (Deltapsi), increased
levels of hydroethidine-oxidizing ROS and stimulation of protein carbonylation.
Co-treatment with the antioxidant alpha-tocopherol, the mitochondrial
permeability transition pore (mPTP) desensitizer cyclosporin A and Necrostatin-1,
a combined inhibitor of Receptor-interacting serine/threonine-protein kinase 1
(RIPK1) and Indoleamine 2,3-dioxygenase (IDO), prevented acidification-induced
cell death. In contrast, the caspase inhibitor zVAD.fmk and the ferroptosis
inhibitor Ferrostatin-1 were ineffective. We conclude that extracellular
acidification induces necroptotic cell death in HEK293 cells and that the latter
involves intracellular acidification, mitochondrial functional impairment,
increased ROS levels, mPTP opening and protein carbonylation. These findings
suggest that acidosis of the extracellular environment (as observed in
mitochondrial disorders, ischemia, acute inflammation and cancer) can induce cell
death via a ROS- and mPTP opening-mediated pathogenic mechanism.
PMID- 29331744
TI - Urinary metabolomics study the mechanism of Taohong Siwu Decoction intervention
in acute blood stasis model rats based on liquid chromatography coupled to
quadrupole time-of-flight mass spectrometry.
AB - Taohong Siwu Decoction (TSD) is a classic prescription in traditional Chinese
medicine and is widely used to promote blood circulation to remove blood stasis.
However, the effect mechanisms are not yet well understood. Here, a urinary
metabolomic approach based on liquid chromatography coupled to quadrupole time-of
flight mass spectrometry (LC/Q-TOF-MS) was conducted to explore the changes in
the endogenous metabolites and to assess the integral efficacy of TSD on acute
blood stasis model rats. Then, parameters for hemorheology and coagulation
functions were detected. Principal component analysis (PCA) and orthogonal
partial least squares discriminate analysis (OPLS-DA) was used to investigate the
global metabolite alterations and to evaluate the preventive effects of TSD in
rats. Potential metabolite markers were found using OPLS-DA and t-test.
Furthermore, metabolic pathway analysis was performed to construct metabolic
networks. The results showed that TSD could significantly decrease whole blood
viscosity and plasma viscosity. It also significantly prolonged partial
thromboplastin time (APPT) and prothrombin time (PT), increased thrombin time
(TT) and lowered fibrinogen content (FIB). Moreover, 24 potential metabolite
markers of acute blood stasis were screened, and the levels were all reversed to
different degrees after TSD administration. In metabolic networks, amino acid
metabolism (arginine and proline metabolism; histidine metabolism; alanine,
aspartate, and glutamate metabolism; phenylalanine, tyrosine, and tryptophan
biosynthesis; phenylalanine metabolism) and lipid metabolism (glycerophospholipid
metabolism; linoleic acid metabolism; alpha-linolenic acid metabolism) were
closely related with the intervention mechanism of TSD on acute blood stasis. The
urinary metabolomic approach can be applied to clarify the mechanism of TSD in
promoting blood circulation to remove acute blood stasis and to provide the
theoretical basis for further research on the therapeutic mechanism of TSD in
clinical practice.
PMID- 29331745
TI - Tumefactive Multiple Sclerosis Masquerading as High Grade Glioma.
AB - Tumefactive multiple sclerosis is a demyelinating lesion that can
radiographically mimic high-grade gliomas during acute episodes, thus affecting
clinical decision making. A delay in appropriate diagnoses can result in
unnecessary invasive resections. The following case is a patient with unilateral
weakness and radiologic findings that were concerning for a high-grade glioma.
Peripheral studies were equivocal. The decision was made to proceed with a
stereotactic biopsy, yielding a definitive diagnosis of tumefactive demyelinating
lesion (TDL). The patient responded robustly to medical management and made a
full clinical recovery. While TDLs and gliomas may look radiologically identical
during acute demyelinating episodes, unlike gliomas, TDLs will demonstrate
evolvement over serial imaging and robust clinical response to high dose
steroids. Clinicians should proceed with caution when considering invasive
procedures with such lesions. Conservative medical management is often sufficient
as seen in this patient. This case highlights the importance of timely diagnosis
and management of TDLs.
PMID- 29331746
TI - Canadian Neurosurgery Educators' Views on Stereotactic Radiosurgery in Residency
Training.
AB - OBJECTIVE: Despite the increasing prominence of stereotactic radiosurgery (SRS)
in treating intracranial and spinal pathologies, there is currently a dearth of
exposure to this modality in the neurosurgical residency. To address this gap,
the aim of this study is to assess neurosurgery educators' views regarding the
current state of SRS exposure, and to identify potential approaches to improve
residency education in this domain. METHODS: Qualitative thematic analysis and
constructivist grounded theory methodology were employed. Semistructured
telephone-based interviews were conducted with current or past residency program
directors, as well as current departmental chairs across neurosurgical
departments in Canada. Interviews were transcribed and subjected to thematic
analysis using open and axial coding. RESULTS: Of the 34 eligible participants,
the overall response rate was 41.1% (14/34), with a 35.3% participation rate
(12/34). Participants represented 9 of the 12 Canadian institutions surveyed. The
majority of participants were current program directors (n = 8), followed by past
program directors (n = 2), and departmental chairs (n = 2). Most respondents 75%
(9/12) view an increasing role for SRS in neurosurgery. Unanimously, respondents
endorse greater exposure to SRS during residency through formal residency
rotations and engagement in interdisciplinary tumor boards to facilitate
involvement in clinical decision-making. CONCLUSIONS: This is the first study to
systematically collate neurosurgery educators' views on SRS in residency in
Canada and demonstrates recognition of the discordance between SRS in practice
and residency training. Neurosurgery educators broadly endorse increased exposure
to this modality. Future work is needed to delineate the requirements necessary
to achieve adequate competency in SRS.
PMID- 29331747
TI - Dural-Based Cavernous Malformation at the Cerebral Convexity: Report of Two
Pediatric Patients.
AB - BACKGROUND: Intracranial cavernous malformations (CMs) are usually located at the
cerebral parenchyma; dural-based CMs outside the middle fossa are rarely
reported. To our knowledge, dural-based CMs located at the cerebral convexity are
even rarer in that only 2 pediatric cases have ever been reported. In this
report, we present 2 extremely rare cases of dural-based CMs at the cerebral
convexity in pediatric patients. The clinical course, radiologic and pathologic
features, treatment, and follow-up are described. CASE DESCRIPTION: The first
case is a 6-year-old boy who presented with headache and vomiting and was found
to have an acute subdural hematoma and space-occupying lesion. Intraoperative
findings and histologic examination were consistent with a CM. He experienced an
uneventful postoperative recovery. The second case is a 43-day-old female neonate
who presented with a progressively enlarging neoplasm at the right occipital
region since birth. Computed tomography of the head performed at admission showed
a slight hyperdense occupying lesion communicating between the intra- and
extracranial cavity through a skull defect. The lesion was resected en bloc and
histologic examination was in accord with a CM. CONCLUSIONS: The clinical
manifestations and radiologic characteristics of dural-based CMs are nonspecific.
Unlike that of their cerebral parenchymal counterparts, the radiologic appearance
of dural-based CMs is confusing and misleading. Surgical resection is the primary
treatment selection for dural-based CMs. In cases with no close relationship to
dural sinuses, complete surgical resection with minimal blood loss and few
neurologic deficits could be easily achieved.
PMID- 29331748
TI - Safety and efficacy of anti-programmed death 1 antibodies in patients with cancer
and pre-existing autoimmune or inflammatory disease.
AB - OBJECTIVE: Patients with autoimmune or inflammatory disease (AID) are susceptible
to immune-related adverse events (irAEs) when treated with immune check-point
inhibitors (ICIs). We decided to analyse the safety and effectiveness of anti-PD
1 antibodies in AID patients and look for an association between the presence of
pre-existing AID and the clinical outcome. METHODS: In a prospective study of the
REISAMIC registry of grade >=2 irAEs occurring in ICI-treated patients, we
studied the associations between pre-existing AID on one hand and irAE-free
survival, overall survival and best objective response rate on the other.
RESULTS: We identified 45 patients with 53 AIDs in REISAMIC. The cancer diagnoses
included melanoma (n = 36), non-small-cell lung cancer (n = 6) and others (n =
3). The most frequent pre-existing AIDs were vitiligo (n = 17), psoriasis (n =
12), thyroiditis (n = 7), Sjogren syndrome (n = 4) and rheumatoid arthritis (n =
2). Twenty patients (44.4%) presented with at least one irAE: eleven of these
were associated with a pre-existing AID ('AID flare'). Treatment with anti-PD-1
antibodies was maintained in 15 of the 20 patients with an irAE. The IrAE-free
survival time was significantly shorter in AID patients (median: 5.4 months) than
in AID-free patients (median: 13 months, p = 2.1 * 10-4). The AID and AID-free
groups did not differ significantly with regard to the overall survival time and
objective response rate (p = 0.38 and 0.098, respectively). CONCLUSION: In
patients treated with anti-PD-1 antibody, pre-existing AID was associated with a
significantly increased risk of irAEs. Our results indicate that cancer
treatments with anti-PD-1 antibodies are just as effective in AID patients as
they are in AID-free patients.
PMID- 29331749
TI - Paediatric dysgerminoma: Results of three consecutive French germ cell tumours
clinical studies (TGM-85/90/95) with late effects study.
AB - METHODS: French patients (<=18years) treated for dysgerminoma between 1985 and
2005 in TGM-85, 90, 95 protocols were included. Treatment was based on primary
unilateral oophorectomy followed by prophylactic lymph node irradiation (1985
1998) or a wait-and-see strategy (1998-2005) for localised completely resected
tumours (pS1) or by platinum-based chemotherapy for advanced diseases. RESULTS:
Forty-eight patients (median age 12.8 years) were included. Six patients had
gonadal dysgenesis. Two had bilateral dysgerminoma. Twenty-eight patients had
loco-regional dissemination, seven with para-aortic lymph nodes. None had distant
metastases. Primary surgery was performed in 47/48 patients. Among the 15
patients with pS1 tumour: seven did not receive adjuvant treatment, six had lymph
node irradiation and two received chemotherapy. Among the 32 patients with
advanced tumour, 31 received cisplatinum-based (n = 25) or carboplatin-based (n =
8) regimen with lymph node irradiation for one of them and one did not receive
adjuvant treatment. With a median follow-up of 14 years, all patients are alive
in complete remission. Five events occurred: 2 contralateral dysgerminomas, 1
peritoneal relapse and 2 second neoplasms (teratoma and melanoma). Bilateral
oophorectomy was necessary for 12 patients. Desire of pregnancy was expressed for
17/36 patients with unilateral oophorectomy, which succeeded in 13 cases (5
medically assisted). 2/17 had ovarian failure. The renal function was normal in
24/25 evaluated patients treated with platinum, ifosfamide or irradiation. The
hearing function was evaluated on 17/36 patients treated with platinum: 12 Brock
grade-0, 3 brock grade-1 and 2 grade-4. CONCLUSION: Dysgerminoma has an excellent
prognosis even in advanced cases with conservative surgery and platinum-based
chemotherapy. However the disease and/or treatment resulted in a high rate of
bilateral oophorectomies and a significant impact on future fertility.
PMID- 29331750
TI - Phosphoinositide 3-kinase inhibitors in advanced breast cancer: A systematic
review and meta-analysis.
AB - Phosphoinositide 3-kinase (PI3K) inhibitors may overcome drug resistance and
improve advanced breast cancer (ABC) outcomes. We conducted a systematic review
and meta-analysis to assess the efficacy and safety of adding a PI3K inhibitor to
the standard of care (SOC) treatment in ABC. The electronic databases Ovid,
PubMed, Cochrane Central Register of Controlled Trials and Embase, were searched
for relevant randomised trials. Pooled hazard ratios (HRs) for progression-free
survival (PFS) and pooled risk ratios (RRs) for objective response rates (ORRs),
disease control rates (DCRs) and toxicity were meta-analysed using the Mantel
Haenszel method and generic inverse variance. Five studies were included. In
unselected patients, the addition of a PI3K inhibitor decreased the risk of
progression by 21% (2329 participants, HR = 0.79; 95% confidence interval [CI],
0.71-0.88). A marginal improvement in ORR (2329 participants, RR = 1.26; 95% CI,
1.01-1.57) and no improvement in DCR (2146 participants, RR = 1.05; 95% CI, 0.94
1.18) were achieved with a significant increase in toxicity of any grade (2386
participants, RR = 1.05; 95% CI, 1.03-1.06) and of grade III and higher (2386
participants, RR = 1.91; 95% CI, 1.76-2.08). A PFS benefit was seen in patients
with and without PI3K pathway activation assessed on tumour and only in patients
with an activated PI3K pathway when it was assessed from the plasma using
circulating tumour DNA (ct-DNA) analysis. The addition of a PI3K inhibitor
decreases the risk of progression in unselected ABC patients and particularly in
patients with an activated PI3K pathway detected on ct-DNA analysis. However,
their significant dose-limiting toxicity is a limiting factor. Selective PI3K
inhibitors are being tested to assess whether these better-tolerated agents have
a role in ABC treatment.
PMID- 29331752
TI - Synthesis of gold(I) phosphine complexes containing the 2-BrC6F4PPh2 ligand:
Evaluation of anticancer activity in 2D and 3D spheroidal models of HeLa cancer
cells.
AB - Newly synthesised mononuclear gold complexes containing the 2-BrC6F4PPh2 ligand
have been fully characterised and their anticancer activity towards five human
tumor [prostate (PC3), glioblastoma (U87MG), cervical (HeLa), fibrosarcoma
(HT1080), ovarian (SKOV-3)] and normal human embryonic kidney (Hek-293T) cell
lines investigated. Some of the synthesised gold complexes displayed higher
cytotoxicity than cisplatin towards PC-3, HeLa and U87MG cells and inhibited the
thioredoxin reductase (TrxR) enzyme, which is considered a potential target for
new compounds in cancer treatment. The more physiologically relevant tumor
spheroid assay demonstrated the superior potency of these gold phosphine
complexes in inhibiting the growth of cervical carcinoma cell line HeLa (3D)
spheroidal models. The mechanism of cell death was shown to be apoptotic cell
death through cell cycle arrest, mitochondrial membrane depolarisation and
increased ROS production.
PMID- 29331751
TI - Comprehensive genomic profiling of head and neck squamous cell carcinoma reveals
FGFR1 amplifications and tumour genomic alterations burden as prognostic
biomarkers of survival.
AB - BACKGROUND: We aimed at identifying deleterious genomic alterations from
untreated head and neck squamous cell carcinoma (HNSCC) patients, and assessing
their prognostic value. PATIENTS AND METHODS: We retrieved 122 HNSCC patients who
underwent primary surgery. Targeted NGS was used to analyse a panel of 100 genes
selected among the most frequently altered genes in HNSCC and potential
therapeutic targets. We selected only deleterious (activating or inactivating)
single nucleotide variations, and copy number variations for analysis. Univariate
and multivariate analyses were performed to assess the prognostic value of
altered genes. RESULTS: A median of 2 (range: 0-10) genomic alterations per
sample was observed. Most frequently altered genes involved the cell cycle
pathway (TP53 [60%], CCND1 [30%], CDKN2A [25%]), the PI3K/AKT/MTOR pathway
(PIK3CA [12%]), tyrosine kinase receptors (EGFR [9%], FGFR1 [5%]) and cell
differentiation (FAT1 [7%], NOTCH1 [4%]). TP53 mutations (p = 0.003), CCND1
amplifications (p = 0.04), CDKN2A alterations (p = 0.02) and FGFR1 amplifications
(p = 0.003), correlated with shorter overall survival (OS). The number of genomic
alterations was significantly higher in the HPV-negative population (p = 0.029)
and correlated with a shorter OS (p < 0.0001). Only TP53 mutation and FGFR1
amplification status remained statistically significant in the multivariate
analysis. CONCLUSION: These results suggest that genomic alterations involving
the cell cycle (TP53, CCND1, CDKN2A), as well as FGFR1 amplifications and tumour
genomic alterations burden are prognostic biomarkers and might be therapeutic
targets for patients with HNSCC.
PMID- 29331753
TI - An iridium (III) complex as potent anticancer agent induces apoptosis and
autophagy in B16 cells through inhibition of the AKT/mTOR pathway.
AB - A new ligand THPDP (THPDP = 11-(6,7,8,9-tetrahydrophenazin-2-yl)dipyrido[3,2
a:2',3'-c]phenazine) and its iridium(III) complex [Ir(ppy)2(THPDP)]PF6 (Ir-1) was
synthesized and characterized by elemental analysis, IR, ESI-MS, 1H NMR and 13C
NMR. The cytotoxicity in vitro of the complex against cancer cells B16, A549, Eca
109, SGC-7901, BEL-7402 and normal NIH 3T3 cell lines was evaluated using MTT
method. The IC50 values of the complex toward B16, A549 and Eca-109 cells are 1.0
+/- 0.02, 1.4 +/- 0.03 and 1.6 +/- 0.06 MUM, respectively. The apoptosis was
investigated with AO/EB and DAPI staining methods. The complex shows strong
ability to inhibit the cell growth in B16, A549 and Eca-109 cells. Ir-1 can
induce apoptosis, increase the intracellular ROS level, and cause a decrease in
the mitochondrial membrane potential. The intracellular Ca2+ level and the
release of cytochrome c were studied under a fluorescent microscope. The cell
invasion and autophagy were also performed, and the cell cycle arrest was assayed
by flow cytometry. The expression of Bcl-2 family proteins, PI3K, AKT, mTOR, P
mTOR was investigated by western blot. The results show that the complex induces
apoptosis through ROS-mediated mitochondria dysfunction and inhibition of
AKT/mTOR pathways. These findings are helpful for design and synthesis of
iridium(III) complexes as potent anticancer drugs.
PMID- 29331754
TI - Synthesis and bioevaluation and doking study of 1H-pyrrolo[2,3-b]pyridine
derivatives bearing aromatic hydrazone moiety as c-Met inhibitors.
AB - Two series of aromatic hydrazone derivatives bearing 1H-pyrrolo[2,3-b]pyridine
moiety (7a-r, 8a-i, 12a-b, 13a-c, 16a-d and 17a-e) were designed, synthesized and
evaluated for the IC50 values against four cancer cell lines (A549, HepG2, MCF
7and PC-3). Two selected compounds (7c and 17e) were further evaluated for the
activity against c-Met, Flt-3, VEGFR-2 and EGFR kinases. The data indicated that
targets compounds were selective for c-Met kinase. And the most promising
compound 7c was further studied in terms of dose-dependent, time-dependent and
cell apoptosis. Most of the compounds showed excellent cytotoxicity activity,
especially the most promising compound 7c with the IC50 values of 0.82 +/- 0.08
MUM, 1.00 +/- 0.11 MUM, 0.93 +/- 0.28 MUM and 0.92 +/- 0.17 MUM against A549,
HepG2, MCF-7 and PC-3 cell lines and 0.506 MUM against c-Met kinase. Structure
activity relationships (SARs) and docking studies indicated that the activities
of the phenyl hydrazone derivatives (7a-r and 8a-i) were superior to that of the
heterocyclic hydrazone series (12a-b, 13a-c, 16a-d and 17a-e). What's more, the
further studies indicated that the target compounds can induce apoptosis of A549
cells and arrest efficiently the cell cycle progression in G2/M phase of A549
cells.
PMID- 29331756
TI - 'You're repulsive': Limits to acceptable drunken comportment for young adults.
AB - BACKGROUND: Researchers have described a 'culture of intoxication' among young
people. Yet drunkenness remains a socially risky practice with potential to evoke
emotions of irritation and even disgust. We consider intoxicated practices that
young adults in Melbourne, Australia, described as distasteful, to identify
contemporary cultural forces that constrain intoxication and limit how it is
enacted. METHOD: Interviews were conducted with 60 participants in Melbourne,
Australia, each with recent drinking experience. Participants were asked to
provide accounts of moments when they regarded their own or others' drunken
comportment as unsociable or unpleasant. Transcripts were analysed to identify
recurrent themes. RESULTS: Despite amusement when recounting drunken antics,
almost everyone in the study identified some discomfort at their own or other's
drunkenness. We describe four interacting domains where lines delineating
acceptable comportment appear be drawn. The first concerns intoxicated practices.
Unpleasant drunken comportment often entailed a sense that the drunk person had
disturbed others through an overflow of the self - extruding intimacy, sexuality,
violence or bodily fluids. The second domain was gendering, with women vulnerable
to being regarded as sexually inappropriate, and men as threatening. Third, the
settings where intoxicated behaviour occurred influenced whether intoxicated
people risked censure. Finally, the relationships between the drunk person and
others, including their respective social positions and drinking patterns, shaped
how they were perceived. CONCLUSION: The capacity of alcohol to render people
more open to the world is both sought and reviled. It is important to recognise
that there remain limits on acceptable drunken comportment, although these are
complex and contingent. These limits are enforced via people's affective
responses to drunkenness. This is form of alcohol harm reduction that occurs
outside of public health intervention. Thus, cultures that constrain drinking
should be supported wherever it is possible to do so without reinforcing
stigmatising identities.
PMID- 29331757
TI - Hedging bets: Applying New Zealand's gambling machine regime to cannabis
legalization.
AB - Cannabis legalization is often falsely depicted as a binary choice between status
quo prohibition and legalizing production and distribution by (regulated) for
profit industry. There are, however, many more prudent architectures for
legalization, such as restricting production and distribution licenses to not-for
profit entities. Wilkins describes how New Zealand applied that concept to
gambling machines and proposes a parallel for cannabis legalization. Greater
investment in proposing good designs along these lines, including attending to
governance structures, would be valuable.
PMID- 29331755
TI - Sphingosine-1-phosphate protects human ovarian follicles from apoptosis in vitro.
AB - OBJECTIVE(S): We aimed to analyze if anti-apoptotic agent sphingosine-1-phosphate
offers protection against in vitro follicle atresia during culture of human
ovarian cortical samples. STUDY DESIGN: A translational research study of ex-vivo
and in-vitro models of human ovarian tissue. MATERIAL AND METHODS: Ovarian
cortical tissue fragments (1 * 0.5 cm) were obtained from young patients (n = 15
mean age +/- SD: 29.4 +/- 2.5) undergoing laparoscopic excision of benign ovarian
cysts. The samples were cultured for 4 days in 24-well format culture plate using
conventional culture techniques. S1P was added to culture media at 200 and 400
MUM concentrations. At the end of culture period the samples were processed for
both histomorphological assessment and detection of apoptosis with
immunohistochemistry and western blot methods using apoptosis marker cleaved
caspase-3. In vitro estradiol (E2) and AMH productions of the samples were
measured with ELISA. Follicle counts were expressed as the mean number of
follicles per mm2. RESULTS: The mean numbers of primordial and secondary
follicles were 3.2 +/- 0.4 and 0.7 +/- 0.2 respectively, in the fresh fixed
uncultured samples. After four days of culture their numbers were significantly
decreased to 0.8 +/- 0.2 (p < 0.01) and 0.1 +/- 0.05 (p < 0.05) respectively, in
the control samples cultured without S1P compared to fresh fixed samples. S1P
treatment decreased follicle atresia and significantly higher number of
primordials (2.3 +/- 0.3, p < 0.01) and secondary follicles (0.5 +/- 0.1, p <
0.05) survived in the samples after 4 day culture period compared to those
cultured without S1P. In line with this there was dose-dependent decrease in the
protein expression of cleaved caspase-3 on western blot and in the number of
apoptotic follicles stained positive for cleaved caspase-3 on
immunohistochemistry in the samples incubated with S1P at 200 and 400 MUM
concentrations. Furthermore, those samples incubated with S1P produced
significantly higher amounts of E2 (2339 +/- 321 vs. 1156 +/- 125 pg/mL
respectively, p < 0.01) compared to control samples. CONCLUSIONS: These results
suggest that S1P promotes follicle survival in human ovarian cortical samples in
vitro.
PMID- 29331758
TI - Caspase-3/MAPK pathways as main regulators of the apoptotic effect of the phyto
mediated synthesized silver nanoparticle from dried stem of Eleutherococcus
senticosus in human cancer cells.
AB - Siberian ginseng (Eleutherococcus senticosus) was used for the synthesis of an
ecofriendly silver nanoparticle (Sg-AgNP), which has exhibited antibacterial,
antioxidant effect and lower cytotoxicity to normal cells in comparison to human
cancer cells. Although, the potential anticancer activity of Sg-AgNP has not been
determined. In this study, two cancer cell lines were used to evaluate the
cytotoxicity and apoptotic effect of Sg-AgNP along with the determination of the
role of the Caspase-3 / p38 MAPK pathways. Results shown that Sg-AgNP reduced the
cell viability of colon cancer cells HT29 and lung cancer cells A549. The
cytotoxic effect was higher than the effect exhibited by a commercial silver
nanoparticle and Cisplatin. Reactive oxygen species were observed to be superior
in both cell lines in the presence of Sg-AgNPs than c-AgNPs and Cisplatin. It was
observed an activation of MAPK14 gene and phosphorylation of p38 MAPK protein in
both cell lines induced by Sg-AgNPs treatment. Furthermore, induction of
morphological changes in the nucleus was done by Sg-AgNPs at 10 MUg/mL in both
cell lines. On the other hands, the activation of CASP3 gene and Caspase-3
protein was observed in HT29 cells but only at protein level in A549 cells. These
results, suggest that Sg-AgNPs anticancer potential activity might be linked to
the induction of apoptosis though the generation of ROS by activation of the
Caspase-3/p38 MAPK pathway.
PMID- 29331759
TI - Astragaloside IV inhibits cell migration and viability of hepatocellular
carcinoma cells via suppressing long noncoding RNA ATB.
AB - Astragaloside IV (AS-IV), the major active component of Astragalus membranaceus,
has shown attractive anticancer effects in certain cancers. However, the roles
and action mechanisms of AS-IV in hepatocellular carcinoma (HCC) are largely
unclear. Long noncoding RNAs (lncRNAs) are recently revealed to have crucial
roles in HCC initiation and progression, but whether lncRNAs participate in the
anticancer roles of AS-IV are unknown. In this study, we demonstrated that AS-IV
significantly downregulated lncRNA-ATB expression in a dose- and time-dependent
manner in HCC cells. Through downregulating lncRNA-ATB, AS-IV repressed
epithelial-mesenchymal transition (EMT) and migration of HCC cells. Furthermore,
through downregulating lncRNA-ATB, AS-IV inactivated IL-11/STAT3 signaling,
induced HCC cell apoptosis, and decreased HCC cell viability. Overexpression of
lncRNA-ATB reversed the effects of AS-IV on HCC cell migration, EMT, cell
apoptosis, cell viability, and IL-11/STAT3 signaling. Taken together, our results
showed that AS-IV inhibited migration and cell viability of HCC cells via
downregulating lncRNA-ATB. Thus, our data provided a novel molecular basis for
the applications of AS-IV in the therapy of HCC.
PMID- 29331760
TI - Inotodiol suppresses proliferation of breast cancer in rat model of type 2
diabetes mellitus via downregulation of beta-catenin signaling.
AB - Breast cancer is amongst the most common cancers causing death of women
worldwide. Breast cancer occurrence is more prominent in people with diabetes. A
recent trend is management of diabetes and cancer has evolved to be natural
remedy including single molecule therapy or combination. In this study, we
investigated the effect of inotodiol on breast cancer growth in diabetic
conditions. Inotodiol is a lanostane triterpenoid found in natural resources like
edible mushroom Inonotus obliquus. We established a rat model of diabetic-breast
cancer by treating female Sprague-Dawley rats with streptazotocin (STZ) at 35
mg/kg followed by induction of breast cancer by administration of 7,12
dimethylbenz(a)anthracene (DMBA) at 10 mg/kg. Diabetes development in
experimental rats was confirmed by measuring fasting blood glucose levels and
oral glucose tolerance test (OGTT), and other biochemical assays were performed.
Histological evaluation of pancreas was performed. The proliferation of breast
tumor was measured by immunohistochemical staining for PCNA, cleaved-caspase-3
and TUNEL staining for apoptosis, and beta-catenin. Results of the study
demonstrate that inotodiol lowered the blood glucose levels in SD rats as well as
reduced plasma levels of cholesterol, triglyceride, and high-density lipoprotein.
The tumor proliferation marker PCNA was reduced by inotodiol. It downregulated
the expression of beta-catenin and its downstream targets (c-Myc and Cyclin D1)
followed by apoptosis induction. Conclusively, results suggest that inotodiol
regulates blood glucose levels in diabetic rats and then controls proliferation
of breast tumor progression by inducing apoptosis via downregulation of beta
catenin signaling. It further suggests that inotodiol can be a preventive
approach in managing dietary chronic conditions like diabetic-breast cancer.
PMID- 29331761
TI - Prevention of articular cartilage degeneration in a rat model of monosodium
iodoacetate induced osteoarthritis by oral treatment with Withaferin A.
AB - Withaferin A (WFA), a highly oxygenated withanolide is used for anti
osteoporotic, fracture healing, obesity control as medicine and dietary
supplement in Ayurveda and Unani medicine but its potential remains to be
investigate for the osteoarthritis studies. In the present study, chondro
protective effects of WFA, under in vitro and in vivo conditions were evaluated.
In-vitro pharmacological activity of WFA was tested on rat articular chondrocytes
through MTT, DPPH, different staining, FACS and translation studies. In-vivo
studies of WFA were evaluated through monosodium iodoacetate (MIA) induced
osteoarthritis studies. DPPH assay, alcian blue and toluidine blue staining
indicated the chondrogenic potential of WFA. Similarly, WFA enhance
chondrogenesis through up-regulation of SOX9 protein. In addition, WFA reduced
the ROS generation, mitochondrial depolarization and apoptosis induced by
inflammatory cytokines IL-1beta and TNF-alpha. Furthermore, WFA treatment in MIA
treated rats alleviated cartilage erosion and improvement in sub-chondral bone
micro-architecture by decrease in Tissue volume (~32%), and trabecular bone
pattern factor (~28%). Taken together, our study provides convincing evidence for
the candidature of WFA (10 mg kg-1 day-1) as a potential agent for the treatment
of cartilage degenerative diseases like osteoarthritis.
PMID- 29331762
TI - Suppression of Capn4 by microRNA-1271 impedes the proliferation and invasion of
colorectal cancer cells.
AB - Accumulating evidence has suggested that calpain small subunit 1 (Capn4) plays an
important role in the development and progression of malignant tumors. However,
little is known about the role of Capn4 in colorectal cancer (CRC). In this
study, we aimed to investigate the potential role of Capn4 in CRC and the
regulation of Capn4 by microRNAs (miRNAs). Here, we found that Capn4 expression
was highly up-regulated in CRC cell lines. Knockdown of Capn4 by siRNA
significantly inhibited the proliferation and invasion of CRC cell lines.
Furthermore, knockdown of Capn4 suppressed Wnt signaling in CRC cells.
Interestingly, Capn4 was found to be a target gene of miR-1271, a tumor
suppressive miRNA. The results showed that miR-1271 negatively regulated Capn4
expression in CRC cells. An inverse correlation between miR-1271 and Capn4 was
also shown in CRC clinical tissues. Moreover, the overexpression of miR-1271
suppressed the proliferation, invasion and Wnt signaling of CRC cells.
Importantly, we found that the restoration of Capn4 expression significantly
reversed the antitumor effects of miR-1271 in CRC cells. Overall, these results
suggest that miR-1271 inhibits the proliferation and invasion of CRC cells by
down-regulating Capn4. Our study suggests that Capn4 and miR-1271 may serve as
potential therapeutic targets for the treatment of CRC.
PMID- 29331763
TI - Inhibition of isoprenylcysteine carboxylmethyltransferase sensitizes common
chemotherapies in cervical cancer via Ras-dependent pathway.
AB - Isoprenylcysteine carboxylmethyltransferase (Icmt) catalyzes the last step of
post-translational protein prenylation, which is essential for the stability and
proper functions of many oncogenic proteins, such as Ras. Despite extensive
studies on the roles of Icmt in tumor transformation and progression, little is
known on the involvement ofIcmt in the development of tumor resistance to
chemotherapy. Here we show the upregulation of Icmt as a persistent response to
chemotherapy in cervical cancer cells. In-depth functional analysis demonstrated
that Icmt inhibition significantly inhibited growth, induced apoptosis and
augmented the inhibitory effects of chemotherapy drugs in cervical cancer in cell
culture system and xenograft mouse model. Importantly, combination of Icmt
specific inhibitor cysmethynil with doxorubicin or paclitaxel at sublethal
concentration achieved almost full inhibition of tumor cell growth and survival.
The remarkable synergy between chemotherapy drugs and Icmt inhibition in cervical
cancer cells is likely due to the additional suppression of Ras and its
downstream signaling pathways. We are the first to demonstrate the contribution
of Icmt in tumor cells in response to chemotherapy. Our work also highlights Icmt
inhibition as a sensitizing strategy for the treatment of cervical cancer or
other Ras-driven tumors.
PMID- 29331764
TI - Synthesis: Small library of hybrid scaffolds of benzothiazole having hydrazone
and evaluation of their beta-glucuronidase activity.
AB - Due to the great biological importance of beta-glucuronidase inhibitors, here in
this study, we have synthesized a library of novel benzothiazole derivatives (1
30), characterized by different spectroscopic methods and evaluated for beta
glucuronidase inhibitory potential. Among the series sixteen compounds i.e.1-6,
8, 9, 11, 14, 15, 20-23 and 26 showed outstanding inhibitory potential with IC50
value ranging in between 16.50 +/- 0.26 and 59.45 +/- 1.12 when compared with
standard d-Saccharic acid 1,4-lactone (48.4 +/- 1.25 uM). Except compound 8 and
23 all active analogs showed better potential than the standard. Structure
activity relationship has been established.
PMID- 29331765
TI - 5,6-Dihydropyrimidine-1(2H)-carbothioamides: Synthesis, in vitro GABA-AT
screening, anticonvulsant activity and molecular modelling study.
AB - Even after considerable advances in the field of epilepsy treatment, convulsions
are inefficiently controlled by standard drug therapy. Herein, a series of
pyrimidine-carbothioamide derivatives 4(a-t) was designed as anticonvulsant
agents by doing some important structural modifications in well-known
anticonvulsant drugs. Two classical animal models were used for the in vivo
anticonvulsant screening, maximum electroshock seizure (MES) and subcutaneous
pentylenetetrazole (scPTZ) models; followed by motor impairment study by rotarod
method. The most active compound 4g effectively suppressed seizure effect in both
the animal models with median doses of 15.6 mg/kg (MES ED50), 278.4 mg/kg (scPTZ
ED50) and 534.4 mg/kg (TD50) with no sign of neurotoxicity. Furthermore, in vitro
GABA-AT enzyme activity assay of 4g showed inhibitory potency (IC50) of 12.23
MUM. The docking study also favored the animal studies.
PMID- 29331766
TI - Roflumilast, type 4 phosphodiesterase inhibitor, attenuates inflammation in rats
with ulcerative colitis via down-regulation of iNOS and elevation of cAMP.
AB - BACKGROUND: Roflumilast (Rof), a phosphodiesterase 4 (PDE4) inhibitor, has been
shown to be an effective agent in inflammatory diseases and marketed for chronic
obstructive pulmonary disease. OBJECTIVE: This study was conducted to examine the
potential anti-inflammatory effects of Rof in dextran sulphate sodium (DSS)
induced ulcerative colitis (UC) in rats and to investigate the molecular
mechanisms underlying these effects. METHODS: Forty male Wistar rats were divided
into four groups: normal control, colitis group (rats received 5% DSS in their
drinking water continuously for 7 days), Rof group, and sulfasalazine (SLZ)
group. The Rof (5 mg/kg) and SLZ (500 mg/kg) groups underwent pretreatment with
DSS one week ahead of DSS challenge and parallel with DSS. Colitis was determined
by assessing colon length, weight loss, histologic colon score, quantifying the
concentration of tumor necrosis factor alpha (TNF-alpha), nitric oxide (NO),
cyclic adenosine monophosphate (cAMP), myeloperoxidase (MPO) activity and
inducible nitric oxide synthase (iNOS) gene expression in colon tissue. RESULTS:
Rof attenuated the severity of colitis as evidenced by increased colon length,
prevention of body weight loss, and improved colon histologic score compared to
DSS group. Rof also suppressed the inflammatory response induced in DSS colitis
group by decreasing colon concentration of TNF-alpha, NO and MPO activity and
down- regulation of iNOS gene expression. The level of cAMP was increased by Rof
compared to DSS group. The obtained results of Rof were comparable to those
exerted by SLZ. CONCLUSION: These findings revealed the beneficial effects of Rof
in alleviating inflammation in DSS colitis.
PMID- 29331767
TI - Lessons from simple marine models on the bacterial regulation of eukaryotic
development.
AB - Molecular cues from environmental bacteria influence important developmental
decisions in diverse marine eukaryotes. Yet, relatively little is understood
about the mechanisms underlying these interactions, in part because marine
ecosystems are dynamic and complex. With the help of simple model systems,
including the choanoflagellate Salpingoeca rosetta, we have begun to uncover the
bacterial cues that shape eukaryotic development in the ocean. Here, we review
how diverse bacterial cues-from lipids to macromolecules-regulate development in
marine eukaryotes. It is becoming clear that there are networks of chemical
information circulating in the ocean, with both eukaryotes and bacteria acting as
nodes; one eukaryote can precisely respond to cues from several diverse
environmental bacteria, and a single environmental bacterium can regulate the
development of different eukaryotes.
PMID- 29331768
TI - The cholinergic anti-inflammatory pathway: an innovative treatment strategy for
respiratory diseases and their comorbidities.
AB - Over the past few decades, it has been clarified that the nervous system and
immune system have overlapping distributions and their interactions are critical
in the regulation of immunological and inflammatory responses. The cholinergic
anti-inflammatory pathway, including the parasympathetic nerve systems and
humoral factors orchestrate the immune responses to protect the body during
infection and tissue injury. Recent investigations have attempted to clarify how
the parasympathetic nerve systems attenuate the systemic inflammatory responses
and identified the alpha7 nicotinic acetylcholine receptor (alpha7nAChR) as a
crucial target for attenuating the release of inflammatory cytokines from
inflammatory cells including macrophages and dendritic cells. This modulatory
circuit pathway possibly exists in the lungs and might be involved in regulating
inflammation and immunity during infection and other inflammatory lung diseases
including asthma and COPD, which means that modulation of the cholinergic anti
inflammatory pathway is a possible therapeutic target for lung diseases.
PMID- 29331769
TI - Source identification of uranium-containing materials at mine legacy sites in
Portugal.
AB - Whilst prior nuclear forensic studies have focused on identifying signatures to
distinguish between different uranium deposit types, this paper focuses on
providing a scientific basis for source identification of materials from
different uranium mine sites within a single region, which can then be
potentially used within nuclear forensics. A number of different tools, including
gamma spectrometry, alpha spectrometry, mineralogy and major and minor elemental
analysis, have been utilised to determine the provenance of uranium mineral
samples collected at eight mine sites, located within three different uranium
provinces, in Portugal. A radiation survey was initially conducted by foot and/or
unmanned aerial vehicle at each site to assist sample collection. The results
from each mine site were then compared to determine if individual mine sites
could be distinguished based on characteristic elemental and isotopic signatures.
Gamma and alpha spectrometry were used to differentiate between samples from
different sites and also give an indication of past milling and mining
activities. Ore samples from the different mine sites were found to be very
similar in terms of gangue and uranium mineralogy. However, rarer minerals or
specific impurity elements, such as calcium and copper, did permit some
separation of the sites examined. In addition, classification rates using linear
discriminant analysis were comparable to those in the literature.
PMID- 29331770
TI - Women's satisfaction with mammography and predictors of participation in an
organized breast cancer screening program: Perspectives of a Local Health Unit in
Rome.
AB - OBJECTIVES: The aims of the study were to evaluate satisfaction with the
mammography service of the Local Health Unit RMA (Rome, Lazio Region) among women
who have attended the program and to identify the predictors of participation.
STUDY DESIGN: Cross-sectional study. METHODS: A telephone-based questionnaire was
administered to women eligible for mammography screening. The respondents were
randomly selected and interviewed by the health center staff. RESULTS: A total of
502 women were interviewed, of which 264 (52.6%) have attended the screening
program at least once. The attendees received the invitation letter more often
than the non-attendees (88.3% vs 77.7%; P = 0.002), were more willing to
participate (85.6% vs 69.3%; P = 0.001), they considered the letter very clear
(15% vs 10.8%; P = 0.003), and information obtained through the hotline
appropriate (64.7% vs 56.7%; P = 0.002). Overall satisfaction was high. Critical
issues were lack of response from the hotline staff, medium-long waiting time for
the results and further examinations. Age >61 years (odds ratio [OR] = 2.747; 95%
confidence interval [CI] = 1.842-4.096), receiving the invitation letter (OR =
2.539; 95% CI = 1.519-4.242), and intention to participate (OR = 3.086; 95% CI =
1.938-4.915) were significantly associated with participation in the screening
program. CONCLUSIONS: Women's satisfaction with mammography is an important
aspect of service utilization. Implementation of strategies to reduce waiting
time, increase operating hours, and improve the invitation procedure and the
hotline service could enhance satisfaction and attendance rate.
PMID- 29331771
TI - Quarantine and the U.S. military response to the Ebola crisis: soldier health and
attitudes.
PMID- 29331772
TI - Alcohol-induced risk behaviors among Brazilian nightclub patrons: a latent class
analysis.
AB - OBJECTIVE: The aim of this study is to identify risk behavior profiles associated
with alcohol consumption among patrons during or just after departure from
nightclubs in Sao Paulo, Brazil. STUDY DESIGN: Cross-sectional survey. METHODS:
The study used a two-stage cluster sampling survey design. Data were collected on
a probabilistic sample of nightclub patrons. Overall, 2422 patrons were
interviewed at the entrance of 31 nightclubs. Latent class analysis (LCA) was
used to identify risk behavior profiles with an emphasis on risky driving,
fights, alcoholic blackouts, and harm and unsafe sex. RESULTS: A 3-class LCA
model was selected, with classes consisting of low (43%), medium (33%), and high
(24%) risk patrons. Compared to patrons in the low-risk class, patrons in the
medium- and high-risk classes were more likely to be men (odds ratio [OR] = 2.2,
95% confidence interval {CI} [1.2-4.0] and OR = 3.2, 95% CI [1.8-5.8],
respectively), to have engaged in binge drinking during the last year (OR = 15.0,
95% CI [7.2-31.3] and OR = 14.3, 95% CI [9.4-21.8]), to be in the highest
socioeconomic stratum (OR = 2.6, 95% CI [1.3-5.1] and OR = 2.0, 95% CI [1.2-3.5])
and to have been interviewed at a hip-hop music nightclub (OR = 2.8, 95% CI [1.1
6.8] and OR = 3.7, 95% CI [1.5-9.1]). CONCLUSIONS: Risk behaviors were not
equally distributed among nightclubs. Individual- and environmental-level
characteristics are associated with higher risk. Alcohol harm reduction, such as
the implementation of a responsible drinking service, should be implemented in
Sao Paulo nightclubs.
PMID- 29331773
TI - Impact of co-exposure of aldrin and titanium dioxide nanoparticles at biochemical
and molecular levels in Zebrafish.
AB - Aldrin (ALD), a persistent-organic-pollutant (POP), an organochlorine-cyclodiene
pesticide is highly toxic in nature. Titanium dioxide nanoparticles (TNP) are
widely used for various industrial applications. Despite the remarkable research
on pesticide toxicity, the work with impact of nanoparticles on POP has been
dealt with marginally. Chemicals co-exist in the environment and exhibit
interactive effects. An investigation was carried out to evaluate the individual
and combined effects of ALD (6 ppm) and TNP (60 ppm) exposure at sub-lethal
concentration for 24 h in zebrafish. Significant reversal of lipid peroxidation
level in liver and brain tissues and restoration in enhanced catalase activity in
all examined tissues were observed in combined group. For other parameters,
combined exposure of ALD and TNP does not show significant reversal action on ALD
toxicity. Further studies are inline to understand combined effects of both to
achieve significant reversal of ALD toxicity by TNP nanoparticles with threshold
concentration of aldrin.
PMID- 29331774
TI - The synergy of Vitamin C with decitabine activates TET2 in leukemic cells and
significantly improves overall survival in elderly patients with acute myeloid
leukemia.
AB - BACKGROUND: Decitabine is widely used in the treatment of acute myeloid leukemia
(AML) in elderly patients. Low-dose Vitamin C has also been indicated to induce
DNA demethylation at the cellular level. However, little is known whether low
dose Vitamin C has a synergistic effect with decitabine in clinic. METHODS: The
effect of combined low-dose Vitamin C and decitabine on cell proliferation, the
cell cycle, apoptosis and the expression level and activity of TET2 was
investigated in HL60 and NB4 human leukemic cells. Additionally, we analyzed the
clinical outcomes of 73 elderly AML patients who received A-DCAG (intravenous
Vitamin C [IVC] plus DCAG [n = 39]) or DCAG (n = 34) treatment. RESULTS: We found
that low-dose Vitamin C and decitabine has a synergistic efficacy on
proliferation, apoptosis, TET2 expression and activity, compared to drug-alone
treatment in HL60 and NB4 cell lines in vitro. In clinic, feasibility and safety
evaluations revealed that patients who received A-DCAG regimen have a higher
complete remission (CR) rate than those who received the DCAG regimen (79.92% vs.
44.11%; P = 0.004) after one cycle of chemotherapy. The median overall survival
(OS) was better in the A-DCAG group compared with the DCAG group (15.3 months vs.
9.3 months, P = 0.039). Patients with adverse cytogenetics did benefit from CR.
There was no clinically significant additional toxicity observed with the
addition of IVC. CONCLUSION: On the basis of these results, the addition of IVC
at low doses to DCAG appeared to improve CR and prolong OS, compared with DCAG,
in elderly patients with AML.
PMID- 29331775
TI - Experience of lecturers with simulation training in midwifery education in
Slovakia.
AB - The simulation training in midwifery has a long tradition. It is aimed at
acquiring basic and advanced practical skills such as performing a certain number
of births, episiotomy and subsequent suture, assisting during breech birth etc.
Midwifery education is currently based on the requirements of the Directives of
the European Union exactly specifying number of performed practical procedures
and approaches (World Health Organisation (WHO) Europe, 2009). The aim of this
paper is to draw attention to the experience with the simulation training from
the teacher's point of view in the study program Midwifery in Slovakia. The
authors describe the locations for training of midwifery skills, training of
basic and advanced midwifery skills using simulation, the types of simulators
available and used and training approaches. They outline the advantages and
disadvantages of using obstetric simulators based on their own experience.
PMID- 29331776
TI - Low-cost screen-printed electrodes based on electrochemically reduced graphene
oxide-carbon black nanocomposites for dopamine, epinephrine and paracetamol
detection.
AB - A green approach for the preparation of carbon black (CB) and electrochemically
reduced graphene oxide composite (ERGO) is described based on screen printed
carbon electrodes (SPCEs) fabricated on poly(ethylene terephthalate) (PET) as
electrochemical sensors. This approach leads to a heterogeneous hydrophilic
surface with high concentration of defect sites according to scanning electron
microscopy, contact angle and Raman spectroscopy measurements. The SPCE/CB-ERGO
sensor was tested with dopamine (DA), epinephrine (EP) and paracetamol (PCM),
exhibiting an enhanced electrocatalytic performance compared to the bare SPCE. It
displayed a wider linear range, lower limit of detection and a remarkably higher
analytical sensitivity, viz. 1.5, 0.13 and 0.028 A L mol-1 for DA, EP and PCM,
respectively, being also capable of simultaneous determination of the three
analytes. Such high performance is demonstration that SPCE/CB-ERGO may serve as
generic platform for cost-effective flexible electrochemical sensors.
PMID- 29331777
TI - Comparing the antifouling effects of activated carbon and TiO2 in ultrafiltration
membrane development.
AB - We use activated carbon (AC) and titanium oxide (TiO2) nanomaterials as the
additives to prepare four polyvinylidene fluoride (PVDF) based ultrafiltration
membranes by nonsolvent induced phase separation. The surface properties (pore
size, porosity, hydrophilicity and roughness) of the membranes are characterized
by scanning electron microscopy, water contact angle measurement, and atomic
force microscopy. The chemical properties of the membranes are evaluated by
Fourier transform infrared spectroscopy with attenuated total reflection and X
ray diffraction. All these additives can improve the surface hydrophilicity and
water permeation flux of the membrane. However, the addition of TiO2
nanoparticles (20-30 nm) results in larger surface porosities and pore sizes,
which causes more severe membrane fouling compared with the neat PVDF membrane.
The PVDF-AC membrane exhibits excellent fouling resistance. Particularly, the
irreversible fouling after blending AC into PVDF reduces dramatically from 40% to
25%. The antifouling performance of the PVDF-AC membrane may result from the
improved hydrophilicity and the favorable surface and structure properties of the
membrane. To the best of our knowledge, this is the first demonstration of the
antifouling function of AC in membrane preparation. This study suggests that AC
could be a new type of nanomaterial for developing antifouling membranes.
PMID- 29331778
TI - Synthesis of a novel narrow-band-gap iron(II,III) oxide/titania/silver silicate
nanocomposite as a highly efficient and stable visible light-driven
photocatalyst.
AB - Ag6Si2O7, a visible light-driven photocatalyst, has attracted considerable
attention owing to its enormous environmental remediation potential. In this
work, a magnetic iron(II,III) oxide/titania/silver silicate (Fe3O4/TiO2/Ag6Si2O7)
nanocomposite was synthesized by anchoring TiO2 and Ag6Si2O7 on the surface of
Fe3O4 nanoparticles. The morphology, crystal structure, as well as the
spectroscopic, magnetic, and photocurrent properties of the as-prepared
Fe3O4/TiO2/Ag6Si2O7 nanocomposite were studied. Methylene blue (MB) was used for
evaluating the photocatalytic performance under simulated visible light. The
Brunauer-Emmett-Teller (BET) surface area, total pore volumes, and average pore
diameter of the Fe3O4/TiO2/Ag6Si2O7 nanocomposite were calculated to be 33.077
m2/g, 0.099 cm3/g, and 15.45 nm, respectively. The Fe3O4/TiO2/Ag6Si2O7
photocatalyst showed a narrow-band-gap (1.38 eV) while exhibiting excellent
photocatalytic performance with a photocurrent of 9.4 uA/cm2 under simulated
visible light. Furthermore, the nanocomposites showed high resistance to
degradation (i.e., more than 80%) after 5 reaction cycles and as a result of high
saturation magnetization (25.51 emu/g), the spent material was easily separated
upon application of a magnetic field. Meanwhile, the photogenerated holes (h+)
and superoxide ions (O2-) were confirmed as the main active species. This novel
photocatalyst is expected to provide a new insight into the design of
photocatalysts with excellent recyclability, high performance, and good
stability.
PMID- 29331779
TI - Superior peroxidase mimetic activity of tungsten disulfide nanosheets/silver
nanoclusters composite: Colorimetric, fluorometric and electrochemical studies.
AB - Developing a novel peroxidase nano-mimetic is a challenging research topic in
biosensing field. Herein, WS2 nanosheets (WS2 NS) decorated with silver
nanoclusters (AgNCs) was introduced as a new nanocomposite with improved
peroxidase mimetic behavior. WS2 NS/AgNCs nanocomposite was synthesized by simple
chemical reduction of silver cations in the presence of WS2 NS. The enhanced
catalytic activity of nanocomposite in chemical and electrochemical reduction of
H2O2 was studied using colorimetry, fluorometry and electrochemical techniques.
Attaching the AgNCs on the surface of WS2 NS effectively improved the catalytic
activity of these nanosheets, which may be connected to the difference of the
Fermi energy levels of coupled nanomaterial. The unequal Fermi levels cause
charge separation between two phases creating highly active sites on the
interface of coupled nanomaterial. Moreover, the new mimetic nanocomposite was
applied for the analysis of glucose in blood, based on its enzymatic oxidation
using glucose oxidase and then, on the measurement of produced H2O2 by sensitive
fluorescence detection system. In optimum condition, a linear association was
found between the generated fluorescence intensity and glucose logarithmic
concentration in the range of 0.05-400 uM, and the limit of detection (3S/m) was
21 nM.
PMID- 29331780
TI - Application of octanohydroxamic acid for liquid-liquid extraction of manganese
oxides and fabrication of supercapacitor electrodes.
AB - MnO2 and Mn3O4 particles were prepared by wet chemical methods and efficiently
dispersed and mixed with multiwalled carbon nanotubes (MWCNT) for the fabrication
of composite MnO2-MWCNT and Mn3O4-MWCNT electrodes for electrochemical
supercapacitors (ES). The problem of particle agglomeration was addressed by
particle extraction through a liquid-liquid interface (PELLI) using
octanohydroxamic acid (OHA) as a new extractor. OHA exhibited remarkable
adsorption on particles due to a bidentate bonding mechanism. The use of OHA
broadened the application of PELLI technology, because it allowed good extraction
of particles from an aqueous phase at high pH. Moreover, OHA allowed efficient
extraction by strong adsorption on particles not only at the liquid-liquid
interface, but also in the bulk of an aqueous phase. Building on the advantages
offered by the PELLI method and OHA as an extractor we found that Mn3O4-MWCNT
electrodes exhibited a remarkably high capacitance of 4.2F cm-2. Another major
finding was that capacitance of Mn3O4-MWCNT electrodes was higher than that of
MnO2-MWCNT electrodes at active mass of 33 mg cm-2. This finding showed
processing advantages of PELLI and paved the way for applications of novel
colloidal and surface modification strategies for the development of advanced ES.
A conceptually new approach has been proposed based on the use of hydroxamic
acids as capping agents for synthesis and extractor molecules for PELLI.
PMID- 29331781
TI - A step-wise self-assembly approach in preparation of multi-responsive
poly(styrene-co-methyl methacrylate) nanoparticles containing spiropyran.
AB - HYPOTHESIS: Surfactant-free emulsion polymerization has become favorable due to
circumventing instability issues reasonably. Incorporation of an appropriate
hydrophilic macroRAFT, could provide controlled in-situ self-assembly via
copolymerization with hydrophobic monomers into polymer particles. So far, this
approach has mostly been studied in dispersion systems and further studies are
needed in emulsions. Beside the corresponding mechanistic studies, the prepared
latex particles would potentially exhibit smart behaviors by choosing stimuli
responsive monomers. EXPERIMENTS: Poly(styrene-co-methyl methacrylate) latexes
were prepared by utilizing pH-responsive polydimethylaminoethyl methacrylate as
the hydrophilic segment through polymerization induced self-assembly (PISA). A
systematic study on the effect of MMA amount, role of smart spiropyran
ethylacrylate (SPEA) comonomer and the synthesized macroRAFT for inducing
efficient assembly has been performed comparatively for the first time. FINDINGS:
SEM and DLS analyses showed the effect of MMA content on the obtaining of
spherical particles with bimodal or monodisperse size distributions in both
series of samples. Kinetic studies through conversion measurements along with GPC
analysis revealed that the incorporation of MMA and SPEA strongly affected the
efficiency of in-situ self-assembly, particle formation and RAFT-controllability
on molecular weights. Ultimately, acido/basochromism, pH-responsivity and UV
responsivity of the prepared latexes were verified and the results showed their
facile and fast multi-responsivity.
PMID- 29331782
TI - Stratification during evaporative assembly of multicomponent nanoparticle films.
AB - HYPOTHESIS: Multicomponent coatings with layers comprising different
functionalities are of interest for a variety of applications, including
electronic devices, energy storage, and biomaterials. Rather than creating such a
film using multiple deposition steps, we explore a single-step method to create
such films by varying the particle Peclet numbers, Pe. Our hypothesis, based on
recent theoretical descriptions of the stratification process, is that by varying
particle size and evaporation rate such that Pe of large and small particles are
above and below unity, we can create stratified films of polymeric and inorganic
particles. EXPERIMENTS: We present AFM on the surface composition of films
comprising poly(styrene) nanoparticles (diameter 25-90 nm) and silica
nanoparticles (diameter 8-14 nm). Previous studies on films containing both
inorganic and polymeric particles correspond to large Pe values (e.g., 120-460),
while we utilize Pe ~ 0.3-4, enabling us to test theories that have been
developed for different regimes of Pe. FINDINGS: We demonstrate evidence of
stratification and effect of the Pe ratio, although our results agree only
qualitatively with theory. Our results also provide validation of recent
theoretical descriptions of the film drying process that predict different
regimes for large-on-top and small-on-top stratification.
PMID- 29331783
TI - Comparative study of novel in situ decorated porous chitosan-selenium scaffolds
and porous chitosan-silver scaffolds towards antimicrobial wound dressing
application.
AB - Dermal defects caused by trauma or disease are challenging to treat due to
difficult-to-treat infections that impair wound healing. Due to the widespread
emergence of drug-resistant bacteria and dwindling discoveries of new
antibiotics, there is currently an urgent need to introduce novel antimicrobials
effective against antibiotic-resistant bacteria without causing damage to host
tissues. As selenium (Se) and silver (Ag) are known for their antimicrobial
properties, we investigated the separate loading of these materials into porous
chitosan/PVA (CS) scaffolds through a simple in situ deposition method to create
two distinct wound dressing materials (CS-Se and CS-Ag). Scaffolds with Se
nanostructures and scaffolds containing Ag nanostructures were characterized and
their activities against S. aureus - (a Gram-positive bacterium), E. coli - (a
Gram-negative bacterium) and Methicillin-Resistant S. aureus (MRSA) - (a multi
drug resistant bacterium) were compared. The release of Ag and Se in vitro was
shown to depend strongly on the release medium used (deionised water, mammalian
or bacterial culture media). Ag-loaded scaffolds showed a significant reduction
in CFUs and cytotoxicity towards fibroblasts while Se-loaded scaffolds showed
abilities to damage bacterial cell membrane and non-toxicity to fibroblast.
Overall, in this study we have demonstrated simple, in situ immobilization porous
CS scaffolds with either Se or Ag nanostructures which could be used to suit
different wound healing applications.
PMID- 29331784
TI - Degradation of dyes by peroxymonosulfate activated by ternary CoFeNi-layered
double hydroxide: Catalytic performance, mechanism and kinetic modeling.
AB - Ternary CoFeNi-layered double hydroxide (CoFeNi-LDH) was synthesized and
initially applied to activate peroxymonosulfate (PMS) for the degradation of
Congo red (CR) and Rhodamine B (RhB). The results show that the CoFeNi-LDH/PMS
system can efficiently degrade nearly 100% of 20 mg/L CR or 20 mg/L RhB within 6-
and 10-min reaction times, respectively. And the catalyst exhibits higher
degradation efficiency on CR than on RhB under identical conditions, which is
confirmed by electron clouds of the highest occupied molecular orbital (HOMO) and
lowest unoccupied molecular orbital (LUMO) performed by DFT calculations.
Quenching tests reveal that SO4- is the dominant active species participating in
the degradation process. Mechanism investigation demonstrates that Co(II)-Co(III)
Co(II) cycle is responsible for activating PMS to generate radicals for dyes
degradation. A dynamic kinetic model is successfully developed to simulate the
concentration profiles of CR and RhB degradation in CoFeNi-LDH/PMS system. The
empirical second order rate constants between SO4- and CR (kSO4-/CR), HO and CR
(kOH/CR), SO4- and RhB (kSO4-/RhB), HO and RhB (kHO/RhB) are determined to be
2.47 * 107, 3.44 * 106, 8.39 * 106 and 2.62 * 107 M-1s-1, respectively. In
addition, toxic assessment using ECOSAR program suggests that the overall
toxicity of CR and RhB decreased after treatment with CoFeNi-LDH/PMS system.
Repeating tests and application of CoFeNi-LDH in different water sources give us
adequate confidence that the as-synthesized CoFeNi-LDH is favorable for the
purification of dye-contaminanted waters in practical.
PMID- 29331785
TI - Causal nature of neighborhood deprivation on individual risk of coronary heart
disease or ischemic stroke: A prospective national Swedish co-relative control
study in men and women.
AB - We studied the association between neighborhood socioeconomic status (SES) and
incidence of coronary heart disease (CHD) or ischemic stroke in the total
population and in full- and half-siblings to determine whether these associations
are causal or a result from familial confounding. Data were retrieved from
nationwide Swedish registers containing individual clinical data linked to
neighborhood of residence. After adjustment for individual SES, the association
between neighborhood SES and CHD showed no decrease with increasing genetic
resemblance, particularly in women. This indicates that the association between
neighborhood SES and CHD incidence is partially causal among women, which
represents a novel finding.
PMID- 29331786
TI - The meaning of community in diverse neighborhoods: Stratification of influence
and mental health.
AB - As the United States diversifies, individuals are increasingly encountering and
managing racial and ethnic difference in their neighboring relationships, thus
challenging the "cultural" basis for consensus on the local meaning of community.
This mixed-methods study considers the ways in which sense of community relates
to mental health in two longstanding racially- and socioeconomically-diverse
neighborhoods. I ask how social resources are distributed within diverse
neighborhoods, integrating survey (N = 243) and interview (N = 60) data to make
observations about both the existence and nature of relationships among the
unique dimensions of sense of community and mental health. Findings indicate that
the influence dimension of sense of community is particularly vital for mental
health, and that whites and homeowners perceive and utilize influence more than
other residents. I use residents' narratives about their experiences to interpret
how influence may relate to mental health and elaborate the ways in which people
of color, renters, and individuals with long tenure comprehend their lack of
influence in diverse neighborhoods.
PMID- 29331787
TI - Val66Met functional polymorphism and serum protein level of brain-derived
neurotrophic factor (BDNF) in acute episode of schizophrenia and depression.
AB - BACKGROUND: Brain-derived neurotrophic factor (BDNF) influences neuron
differentiation during development as well as the synaptic plasticity and neuron
survival in adulthood. BDNF has been implicated in the pathogenesis of
schizophrenia and depression. Val66Met polymorphism and BDNF serum level are
potential biomarkers in neuropsychiatric disorders. The aim of this study was to
determine the effect of BDNF gene Val66Met functional polymorphism on serum BDNF
concentration in patients with schizophrenia, during depression episode and in
healthy control group. METHODS: 183 participants were recruited (61 patients with
depressive episode, 56 females with schizophrenia, 66 healthy controls) from
Polish population. Serum BDNF levels were measured using ELISA method. Val66Met
polymorphism was genotyped using PCR- RFLP method. RESULTS: Serum BDNF levels
were not associated with Val66Met polymorphism in either of the groups. A
significant increase of BDNF level in schizophrenia (p = 0.0005) and depression
(p = 0.026) comparing to the control group has been observed. CONCLUSIONS: Our
results suggest that the functional Val66Met BDNF polymorphism is not associated
with BDNF serum levels, which is in line with previous findings. Replication
studies on larger groups are needed.
PMID- 29331788
TI - Curcumin inhibits cardiac hypertrophy and improves cardiovascular function via
enhanced Na+/Ca2+ exchanger expression after transverse abdominal aortic
constriction in rats.
AB - BACKGROUND: This study tested the hypothesis that inhibition of cardiac
hypertrophy and preservation of cardiac/endothelial function by the natural
yellow pigment curcumin are associated with upregulated expression of Na+/Ca2+
exchanger (NCX) after transverse aortic constriction (TAC). METHODS: Male Wistar
rats were subjected to TAC for 10 weeks and curcumin (50 mg/kg/day) was fed by
gastric gavage during TAC. Expression of NCX and endothelial nitric oxide
synthase (eNOS) was analyzed by Western blot and immunohistochemistry. RESULTS:
Compared with the animals in the TAC group, curcumin significantly increased the
survival rate and reduced the ratio of heart or left ventricle (LV) to body
weight and the cross sectional area of cardiomyocytes. In coincidence with
improved LV systolic pressure and reduced LV end-diastolic pressure, curcumin
significantly reduced LV end-systolic and diastolic diameter/dimension, and
enhanced LV ejection fraction and LV fractional shortening as measured by
echocardiography. Furthermore, endothelium-dependent relaxation of aortic rings
in response to acetylcholine was significantly improved by curcumin. Along with
these modifications, the expression and localization of NCX and eNOS in the
myocardium and vascular endothelium were significantly upregulated by curcumin.
The protective effect of curcumin on endothelium-dependent relaxation was partly
blocked by pretreatment with the NCX inhibitor, KB-R7943. CONCLUSIONS: These
results demonstrate that inhibition of cardiac hypertrophy, improvement of
cardiac systolic/diastolic function and preservation of vascular endothelium by
curcumin might be associated with upregulated NCX expression level in response to
increased afterload.
PMID- 29331789
TI - Anticonvulsant activities of alpha-asaronol ((E)-3'-hydroxyasarone), an active
constituent derived from alpha-asarone.
AB - BACKGROUND: Epilepsy is one of chronic neurological disorders that affects 0.5
1.0% of the world's population during their lifetime. There is a still
significant need to develop novel anticonvulsant drugs that possess superior
efficacy, broad spectrum of activities and good safety profile. METHODS: alpha
Asaronol and two current antiseizure drugs (alpha-asarone and carbamazepine
(CBZ)) were assessed by in vivo anticonvulsant screening with the three most
employed standard animal seizure models, including maximal electroshock seizure
(MES), subcutaneous injection-pentylenetetrazole (PTZ)-induced seizures and 3
mercaptopropionic acid (3-MP)-induced seizures in mice. Considering drug safety
evaluation, acute neurotoxicity was assessed with minimal motor impairment
screening determined in the rotarod test, and acute toxicity was also detected in
mice. RESULTS: In our results, alpha-asaronol displayed a broad spectrum of
anticonvulsant activity (ACA) and showed better protective indexes (PI = 11.11 in
MES, PI = 8.68 in PTZ) and lower acute toxicity (LD50 = 2940 mg/kg) than its
metabolic parent compound (alpha-asarone). Additionally, alpha-asaronol displayed
a prominent anticonvulsant profile with ED50 values of 62.02 mg/kg in the MES and
79.45 mg/kg in the sc-PTZ screen as compared with stiripentol of ED50 of 240
mg/kg and 115 mg/kg in the relevant test, respectively. CONCLUSION: The results
of the present study revealed alpha-asaronol can be developed as a novel
molecular in the search for safer and efficient anticonvulsants having
neuroprotective effects as well as low toxicity. Meanwhile, the results also
suggested that alpha-asaronol has great potential to develop into another new
aromatic allylic alcohols type anticonvulsant drug for add-on therapy of Dravet's
syndrome.
PMID- 29331790
TI - C-Phycocyanin: Cellular targets, mechanisms of action and multi drug resistance
in cancer.
AB - C-Phycocyanin (C-PC) has been shown to be promising in cancer treatment; however,
although several articles detailing this have been published, its main mechanisms
of action and its cellular targets have not yet been defined, nor has a detailed
exploration been conducted of its role in the resistance of cancer cells to
chemotherapy, rendering clinical use impossible. From our extensive examination
of the literature, we have determined as our main hypothesis that C-PC has no one
specific target, but rather acts on the membrane, cytoplasm, and nucleus with
diverse mechanisms of action. We highlight the cell targets with which C-PC
interacts (the MDR1 gene, cytoskeleton proteins, and COX-2 enzyme) that make it
capable of killing cells resistant to chemotherapy. We also propose future
analyses of the interaction between C-PC and drug extrusion proteins, such as
ABCB1 and ABCC1, using in silico and in vitro studies.
PMID- 29331791
TI - Magnesium sulfate reduces formalin-induced orofacial pain in rats with normal
magnesium serum levels.
AB - BACKGROUND: In humans, orofacial pain has a high prevalence and is often
difficult to treat. Magnesium is an essential element in biological a system
which controls the activity of many ion channels, neurotransmitters and enzymes.
Magnesium produces an antinociceptive effect in neuropathic pain, while in
inflammatory pain results are not consistent. We examined the effects of
magnesium sulfate using the rat orofacial formalin test, a model of trigeminal
pain. METHODS: Male Wistar rats were injected with 1.5% formalin into the
perinasal area, and the total time spent in pain-related behavior (face rubbing)
was quantified. We also spectrophotometrically determined the concentration of
magnesium and creatine kinase activity in blood serum. RESULTS: Magnesium sulfate
administered subcutaneously (0.005-45mg/kg) produced significant antinociception
in the second phase of the orofacial formalin test in rats at physiological serum
concentration of magnesium. The effect was not dose-dependent. The maximum
antinociceptive effect of magnesium sulfate was about 50% and was achieved at
doses of 15 and 45mg/kg. Magnesium did not affect increase the levels of serum
creatine kinase activity. CONCLUSIONS: Preemptive systemic administration of
magnesium sulfate as the only drug can be used to prevent inflammatory pain in
the orofacial region. Its analgesic effect is not associated with magnesium
deficiency.
PMID- 29331792
TI - Candesartan, angiotensin II type 1 receptor blocker is able to relieve age
related cognitive impairment.
AB - BACKGROUND: Candesartan is one of the standard antihypertensive drug belonging to
AT1R angiotensin receptor blockers (ARBs) group. Beneficial effects of this drug
in the treatment of hypertension are well recognized. In this study we tested a
hypothesis that candesartan could alleviate age-related memory decline. METHODS:
Aged and young rats have been treated with candesartan (0.1mg kg-1) for 21days
and then underwent a battery of behavioral tests: for assessment of long-term
memory (Passive avoidance test - PA), recognition memory (Object recognition test
- OR), locomotor functions (Open field - OF) and anxiety behavior (Elevated plus
maze - EPM). RESULTS: Aged rats (2-years-old) displayed clear declining tendency
in the retrieval of passive avoidance behavior showing thus increased forgetting.
Prolonged administration of candesartan significantly (p<0.01) reversed this
phenomenon causing recall measured as the avoidance latency, and surprisingly
also showed the tendency to recall deterioration observed in the young rats. More
optimistic results were achieved in the OR, where candesartan significantly
improved recognition memory (p<0.001) of aged rats who performed even better than
the young ones (p<0.05). CONCLUSIONS: It appears that candesartan potently
abolishes some kinds of aging-induced memory impairments and cognitive declines
in aged rats, but in some circumstances it may even could increase the damage of
memory. It seems that the use of sartans in the treatment of hypertension for
patients with associated cognitive impairment, or for people in risk groups for
such disorders can be an interesting alternative.
PMID- 29331793
TI - Moderate-dose simvastatin therapy potentiates the effect of vitamin D on thyroid
autoimmunity in levothyroxine-treated women with Hashimoto's thyroiditis and
vitamin D insufficiency.
AB - BACKGROUND: Vitamin D preparations reduce titers of thyroid antibodies in women
with autoimmune thyroiditis. The same effect was induced by high-dose, but not
moderate-dose-, statin therapy. No previous study has investigated the impact of
concomitant treatment with a statin and vitamin D on thyroid autoimmunity.
METHODS: The study included three matched groups of women with Hashimoto's
thyroiditis and low vitamin D status. Groups B (n=19) and C (n=20) were treated
with vitamin D (2000 IU daily). Because of coexistent hypercholesterolemia,
groups A (n=18) and B received simvastatin (40mg daily). Plasma lipids, serum
levels of thyrotropin, free thyroid hormones and 25-hydroxyvitamin D, as well as
titers of thyroid peroxidase and thyroglobulin antibodies were measured at the
beginning of the study and 6 months later. RESULTS: At baseline, 25
hydroxyvitamin D levels inversely correlated with titers of thyroid antibodies.
In groups A and B, simvastatin reduced plasma levels of total and LDL
cholesterol. Simvastatin produced no effect on thyroid antibody titers. Vitamin D
decreased titers of thyroid peroxidase antibodies, as well as tended to decrease
titers of thyroglobulin antibodies. Simvastatin-vitamin D combination therapy
reduced serum titers of thyroid peroxidase and thyroglobulin antibodies and this
effect was stronger than the effect of simvastatin and vitamin D administered
alone. Treatment-induced changes in thyroid antibody titers correlated with
baseline antibody titers, baseline levels of 25-hydroxyvitamin and treatment
induced changes in 25-hydroxyvitamin. CONCLUSIONS: The obtained results indicate
that simvastatin may potentiate the impact of vitamin D on thyroid autoimmunity
in vitamin D-deficient women with Hashimoto's thyroiditis.
PMID- 29331794
TI - Melatonin suppresses eosinophils and Th17 cells in hamsters treated with a
combination of human liver fluke infection and a chemical carcinogen.
AB - BACKGROUND: The combination of Opisthorchis viverrini (OV) infection and chemical
carcinogen induces cholangiocarcinoma (CCA) in hamsters via inflammation-mediated
mechanisms. Thus, suppression of inflammatory cells at the initial stages of CCA
development would be of benefit. We aimed to investigate whether IL-17-producing
CD4+ T cells (Th17) and CD4+ Foxp3+ T cells (Treg) are involved in the early
stages of CCA genesis and can be targeted for suppression by melatonin. METHODS:
Inflammation, an initial stage of CCA development, was induced in hamsters by a
combination of O. viverrini infection and N-nitrosodimethylamine (NDMA)
administration. Melatonin (50mg/kg) was additionally administered to one group
for the 30days of the experiment. Liver tissue-resident T cells were investigated
using immunostaining, western blotting, and real-time PCR. RESULTS: OV+NDMA
induced CCA tissues showed significantly higher numbers of inflammatory cells,
especially eosinophils, bile duct proliferation and IL-17+ cell infiltration
compared to normal livers. Expression of Foxp3 was localized in the bile duct
epithelial cells, and especially in the bile duct hyperplasia. Accumulation of
CD4+ and IL-17+ cells and intense staining of the Foxp3+ marker were consistent
with their protein levels. Infiltration of IL-17+ inflammatory cells and Foxp3+
cells, as well as increases in their transcription expression levels, were
significantly lower in the melatonin-treated group. In contrast, increased CD4+
cell infiltration and TNF-alpha expression were also observed through melatonin
treatment. CONCLUSION: Melatonin exerts an immunomodulatory effect, suppressing
eosinophils and Th17 cells and expression of Foxp3, but enhancing CD4+ cells and
TNF-alpha. This suggests that melatonin may be used for CCA chemoprevention.
PMID- 29331795
TI - Development and validation of an UHPLC-MS/MS approach for simultaneous
quantification of five bioactive saponins in rat plasma: Application to a
comparative pharmacokinetic study of aqueous extracts of raw and salt-processed
Achyranthes bidentata.
AB - A simple, accurate and sensitive ultra high-performance liquid chromatography
tandem mass spectrometry approach was established for the simultaneous
determination of beta-ecdysterone, 25S-inokosterone, ginsenoside Ro,
chikusetsusaponin IV and chikusetsusaponin IVa in rat plasma after oral
administration of raw and salt-processed Achyranthes bidentata extract. The
saponins were completely separated on a Waters BEH C18 UHPLC column by using
acetonitrile/0.1% formic acid-water as mobile phases. The mass analysis was
performed in a triple quadrupole mass spectrometer using multiple reaction
monitoring (MRM) with negative scan mode. The sample preparations for protein
removal were accomplished using a simple acetonitrile precipitation method. The
calibration curves displayed good linearity (r2 > 0.9998) with the concentration
ranges of 24.4-6100 ng mL-1, 25.6-6400 ng mL-1, 20.4-8500 ng mL-1, 21.6-5400 ng
mL-1, 21.6-6100 ng mL-1 for the five saponins, respectively. The intra-day and
inter-day precisions (RSD) of the five saponins were less than 3.95% and the bias
of the accuracies ranged from -4.50% to 4.84%. The extraction recoveries of the
five saponins ranged from 95.2% to 104.8% and the matrix effects were
satisfactory. In comparison with the raw group, the parameters of Cmax and AUC0-t
of beta-ecdysterone, 25S-inokosterone, ginsenoside Ro, and chikusetsusaponin IVa
elevated remarkably (p < 0.05) after oral delivery of the extract of salt
processed Achyranthes bidentata, which revealed that salt-processing could
increase bioavailability of beta-ecdysterone, 25S-inokosterone, ginsenoside Ro
and chikusetsusaponin IVa.
PMID- 29331796
TI - Determination of meropenem in endotracheal tubes by in-tube solid phase
microextraction coupled to capillary liquid chromatography with diode array
detection.
AB - Meropenem is a widely used antimicrobial for the treatment of infections
associated with the use of invasive medical devices in intensive care unit
patients. These treatments are not always effective, in fact, in-vitro studies
have demonstrated the difficulty of antimicrobials to penetrate into the biofilm,
however in-vivo studies of the effect of these compounds is a trend, mostly
because of the complexity of pulmonary samples extracted from ETTs. Therefore,
the objective of this study was to evaluate in-tube solid phase microextraction
(in-tube SPME) coupled to capillary liquid chromatography (CapLC) with DAD to
determine meropenem in ETTs in order to estimate the penetration capability into
the biofilm. Firstly, different parameter affecting in-tube SPME, such as
processed sample volume, capillary length, flow and capillary coating were
studied. The best analytical response was achieved by processing 500 MUL of
standards/samples at 9 MUL/seg with a 60-cm capillary column coated with 35%
diphenyl 65%-polydimethylsiloxane. Under these conditions, the analytical
performance of in-tube SPME-CapLC-DAD, using acetonitrile-water in gradient mode
as mobile phase, showed satisfactory results for estimation of meropenem in terms
of sensitivity (LOD = 3 MUg/L) and precision (RSD < 10%). Once the experimental
conditions were stablished for in-tube SPME, the extraction of meropenem from the
ETTs was studied. Liquid extraction, vortex-assisted liquid extraction (VALE) and
ultrasound-extraction (UAE) extraction were tested. The results indicated that
meropenem could be quantitatively extracted (91 +/- 6%) from ETTs, for its
subsequent determination by in-tube SPME-CapLC-DAD using water as extraction
solvent and 1 min as extraction time. Finally, samples from ETTs used for
critically ill patients with different antimicrobial treatments were analysed
with successful results.
PMID- 29331797
TI - Application of polyacrylamide gel as a new membrane in electromembrane extraction
for the quantification of basic drugs in breast milk and wastewater samples.
AB - Introducing new membranes with green chemistry approach seems to be a great
challenge for the development of a practical method in separation science. In
this regard, for the first time, polyacrylamide gel as a new membrane in
electromembrane extraction (EME) was used for the extraction of three model basic
drugs (pseudoephedrine (PSE), lidocaine (LID), and propranolol (PRO)), followed
by HPLC-UV. In comparison with conventional EME, in this method neither organic
solvent nor carrier agents were used for extraction of mentioned drugs. Different
variables for fabrication of polyacrylamide gel and extraction process were
evaluated. Polyacrylamide gel (containing 12% (w/v) acrylamide, and 3.0% (w/w)
bisacrylamide) with 2 mm thickness at pH = 1.5 was fabricated as membrane. The
drugs were extracted from aqueous samples, through a polyacrylamide gel membrane,
to an aqueous acceptor phase on membrane. Under the optimized extraction
conditions (Voltage: 85 V, extraction time: 28 min, acceptor phase's pH: 4.0, and
donor phase's pH: 7.0) limits of quantification and detection were in the ranges
of 1.0-20.0 ng mL-1 and 0.3-6.0 ng mL-1, respectively. Applying the proposed
method to determine and quantify intended drugs in breast milk, and wastewater
samples have revealed acceptable results.
PMID- 29331798
TI - Engaging students in a community of learning: Renegotiating the learning
environment.
AB - Promoting student engagement in a student led environment can be challenging.
This article reports on the process of design, implementation and evaluation of a
student led learning approach in a small group tutorial environment in a three
year Bachelor of Nursing program at an Australian university. The research
employed three phases of data collection. The first phase explored student
perceptions of learning and engagement in tutorials. The results informed the
development of a web based learning resource. Phase two centred on implementation
of a community of learning approach where students were supported to lead
tutorial learning with peers. The final phase constituted an evaluation of the
new approach. Findings suggest that students have the capacity to lead and engage
in a community of learning and to assume greater ownership and responsibility
where scaffolding is provided. Nonetheless, an ongoing whole of course approach
to pedagogical change would better support this form of teaching and learning
innovation.
PMID- 29331799
TI - The deepwater horizon oil spill coast guard cohort study: A cross-sectional study
of acute respiratory health symptoms.
AB - INTRODUCTION: Over 8500 United States Coast Guard (USCG) personnel were deployed
in response to the Deepwater Horizon (DWH) oil spill; however, human respiratory
effects as a result of spill-related exposures are relatively unknown. METHODS:
USCG personnel who responded to the DWH oil spill were queried via survey on
exposures to crude oil and oil dispersant, and acute respiratory symptoms
experienced during deployment. Adjusted log binomial regressions were used to
calculate prevalence ratios (PRs) and 95% confidence intervals (CI),
investigating the associations between oil spill exposures and respiratory
symptoms. RESULTS: 4855 USCG personnel completed the survey. More than half
(54.6%) and almost one-fourth (22.0%) of responders were exposed to crude oil and
oil dispersants, respectively. Coughing was the most prevalent symptom (19.4%),
followed by shortness of breath (5.5%), and wheezing (3.6%). Adjusted analyses
showed an exposure-response relationship between increasing deployment duration
and likelihood of coughing, shortness of breath, and wheezing in the pre-capping
period. A similar pattern was observed in the post-capping period for coughing
and wheezing. Adjusted analyses revealed increased PRs for coughing (PR=1.92),
shortness of breath (PR=2.60), and wheezing (PR=2.68) for any oil exposure.
Increasing frequency of inhalation of oil was associated with increased
likelihood of all three respiratory symptoms. A similar pattern was observed for
contact with oil dispersants for coughing and shortness of breath. The
combination of both oil and oil dispersants presented associations that were much
greater in magnitude than oil alone for coughing (PR=2.72), shortness of breath
(PR=4.65), and wheezing (PR=5.06). CONCLUSIONS: Results from the present study
suggested strong relationships between oil and oil dispersant exposures and acute
respiratory symptoms among disaster responders. Future prospective studies will
be needed to confirm these findings.
PMID- 29331800
TI - Nucleus accumbens mu opioid receptors regulate context-specific social
preferences in the juvenile rat.
AB - The MU opioid receptor (MOR) in the nucleus accumbens (NAc) is involved in
assigning pleasurable, or hedonic value to rewarding stimuli. Importantly, the
hedonic value of a given rewarding stimulus likely depends on an individual's
current motivational state. Here, we examined the involvement of MORs in the
motivation to interact with a novel or a familiar (cage mate) conspecific in
juvenile rats. First, we demonstrated that the selective MOR antagonist CTAP
administered into the NAc reduces social novelty preference of juvenile males, by
decreasing the interaction time with the novel conspecific and increasing the
interaction time with the cage mate. Next, we found that a 3-h separation period
from the cage mate reduces social novelty preference in both juvenile males and
females, which was primarily driven by an increase in interaction time with the
cage mate. Last, we showed that MOR agonism (intracerebroventricularly or in the
NAc) restored social novelty preference in juvenile males that did not show
social novelty preference following social isolation. Taken together, these data
support a model in which endogenous MOR activation in the NAc facilitates the
relative hedonic value of novel over familiar social stimuli. Our results may
implicate the MOR in neuropsychiatric disorders characterized by altered social
motivation, such as major depression and autism spectrum disorder.
PMID- 29331802
TI - Hair cortisol and work stress: Importance of workload and stress model (JDCS or
ERI).
AB - Hair cortisol concentrations (HCCs) are a potential physiological indicator of
work related stress. However, studies that tested the relationship between HCC
and self-reported stress in a work setting show mixed findings. This may be
because few studies used worker samples that experience prolonged stress.
Therefore, we compared a high workload sample (n = 81) and a normal workload
sample (n = 91) and studied whether HCC was related to: (i) high job demands, low
control, and low social support (JDCS model), and (ii) high effort, low reward,
and high overcommitment (ERI model). Results showed that self-reported stress
related to HCC only in the high workload sample and only for the variables of the
ERI model. We found that HCC was higher when effort was high, reward low, and
overcommitment high. An implication of this study is that a certain stress
threshold may need to be reached to detect a relationship between self-reported
stress and physiological measures such as HCC.
PMID- 29331801
TI - Stressful life events, relationship stressors, and cortisol reactivity: The
moderating role of suppression.
AB - Stressful life events (SLEs) are exceedingly common and have been associated with
a range of psychological disorders, perhaps through dysregulation in the
hypothalamic-pituitary-adrenal (HPA) axis. The use of certain emotion regulation
strategies in response to stress, such as expressive suppression and cognitive
reappraisal, has additionally been linked to heightened HPA axis reactivity to
acute stress. However, it is unclear how emotion regulation may interact with
SLEs to affect HPA axis reactivity, particularly concerning relationship
stressors (RSs). Using cross-sectional data from 117 men and 85 women aged 18-55
years old (M = 39.9 +/- 10.7), we investigated whether trait use of suppression
or reappraisal interacted with recent negatively perceived SLEs and relationship
stressors to impact HPA axis response to an acute stressor. Separate area under
the curve and linear mixed models revealed that trait suppression interacted with
SLEs and RSs to predict cortisol response to stress, while reappraisal did not.
Findings indicate higher trait expressive suppression may influence the cortisol
response to acute stress after exposure to more recent stressful events,
particularly when those stressful events include relationship stress.
PMID- 29331803
TI - Caspases are key regulators of inflammatory and innate immune responses mediated
by TLR3 in vivo.
AB - Understanding the key regulators which impact the innate immune response during
initial phases of tissue injury, can advance the use of therapeutic approaches
which aim at attenuating inflammation and organ damage. Recognition of microbial
components by TLRs, initiates the transcription of innate immune signal pathways,
that induce the expression of key inflammatory mediators: cytokines, chemokines
and adhesion molecules. Beside regulating apoptotic cell death, recent studies
have revealed distinct roles for caspases in the optimal production of
inflammatory cytokines and host defense against injurious infections. Whether
caspases can play an immune regulatory role in vivo has not been sufficiently
investigated. This study aims to explore whether the pan caspase inhibitor z-VAD
fmk can control inflammation and cytokine production subsequent to challenging
the innate immunity of the exocrine secretory tissues in vivo. Submandibular
glands (SMGs) of the C57BL/6 mice were challenged with the TLR3 stimulant:
polyinosinic-polycytidylic acid (poly (I:C)). Results obtained from the current
study provide evidence that caspases can control immune responses downstream of
TLR3 ligation. The present work proposes a novel mechanism that can prevent
overactivation of the innate immunity, which typically leads to fatal immune
disorders.
PMID- 29331804
TI - Toll-like receptor 9 antagonist suppresses humoral immunity in experimental
autoimmune myasthenia gravis.
AB - Recent studies have demonstrated the important role of toll-like receptor 9
(TLR9) signalling in autoimmune diseases, but its role in myasthenia gravis (MG)
has not been fully established. We show herein that blocking TLR9 signalling via
the suppressive oligodeoxynucleotide (ODN) H154 alleviated the symptoms of
experimental autoimmune myasthenia gravis (EAMG). With the downregulation of
dendritic cells (DCs), TLR9 interruption reduced follicular helper T cells (Tfh)
and germinal centre (GC) B cells, leading to decreased antibody production. In
addition, TLR9+ B cells as well as total B cells in the spleen were inhibited by
H154. These findings highlight the critical role of TLR9 in EAMG and suggest that
the inhibition of the TLR9 pathway might be a potential pharmacological strategy
for the treatment of myasthenia gravis.
PMID- 29331805
TI - Synthesis, characterization and anticancer activity in vitro and in vivo
evaluation of an iridium (III) polypyridyl complex.
AB - An iridium (III) complex [Ir(ppy)2(BDPIP)]PF6 (Ir-1) was reported to show high
anticancer activity and may be used as a potent anticancer drug. In the current
study, we designed and synthesized a novel iridium (III) complex and evaluated
its potential inhibitory effect on the cancer cell growth in vitro and in vivo.
This complex was found to display high cytotoxic activity in vitro and in vivo
against A549 cell with a low IC50 value of 3.6 +/- 0.3 MUM and inhibiting
percentage of tumor growth is 63.84% compared with the control. The complex also
exhibited potencies superior to that of cisplatin toward A549 cell in vitro and
in vivo. Further studies revealed that the complex can induce apoptosis and
autophagy, enhance the ROS level, cause a decrease in the mitochondrial membrane
potential and inhibit the cell invasion. Our findings indicated that the complex
induced apoptosis in A549 through mitochondria dysfunction and PI3K/AKT/mTOR
signaling pathways.
PMID- 29331806
TI - Unifying in vitro and in vivo IVT mRNA expression discrepancies in skeletal
muscle via mechanotransduction.
AB - The translational efficiency of an in vitro transcribed (IVT) mRNA was measured
upon delivery to primary skeletal muscle cells and to a mouse model system,
towards the development of a predictive in vitro assay for the screening and
validation of intramuscular mRNA-based vaccines. When IVT mRNA was delivered
either naked or complexed with novel aminoglycoside-based delivery vehicles,
significant differences in protein expression in vitro and in vivo were observed.
We hypothesized that this previously anticipated discrepancy was due to
differences in the mechanism of IVT mRNA endosomal entry and release following
delivery. To address this, IVT mRNA was fluorescently labeled prior to delivery,
to visualize its distribution. Colocalization with endosomal markers indicated
that different entry pathways were utilized in vivo and in vitro, depending on
the delivery vehicle, resulting in variations in protein expression levels. Since
extracellular matrix stiffness (ECM) influences mRNA entry, trafficking and
release, the effect of mechanotransduction on mRNA expression was investigated in
vitro upon delivery of IVT mRNA alone, and complexed with delivery vehicles to
skeletal muscle cells grown on ~10 kPa hydrogels. This in vitro hydrogel model
more accurately recapitulated the results obtained in vivo upon IM injection,
indicating that this approach may assist in the characterization of mRNA based
vaccines.
PMID- 29331807
TI - Clay nanoparticles for regenerative medicine and biomaterial design: A review of
clay bioactivity.
AB - Clay nanoparticles, composites and hydrogels are emerging as a new class of
biomaterial with exciting potential for tissue engineering and regenerative
medicine applications. Clay particles have been extensively explored in polymeric
nanocomposites for self-assembly and enhanced mechanical properties as well as
for their potential as drug delivery modifiers. In recent years, a cluster of
studies have explored cellular interactions with clay nanoparticles alone or in
combination with polymeric matrices. These pioneering studies have suggested new
and unforeseen utility for certain clays as bioactive additives able to enhance
cellular functions including adhesion, proliferation and differentiation, most
notably for osteogenesis. This review examines the recent literature describing
the potential effects of clay-based nanomaterials on cell function and examines
the potential role of key clay physicochemical properties in influencing such
interactions and their exciting possibilities for regenerative medicine.
PMID- 29331809
TI - Environmental behavior of coated NMs: Physicochemical aspects and plant
interactions.
AB - The application of nanomaterials (NMs) depends on several characteristics,
including polydispersity, shape, surface charge, and composition, among others.
However, the specific surface properties of bare NMs induce aggregation, reducing
their utilization. Thus, different surface coverages have been developed to avoid
or minimize NMs aggregation, making them more stable for the envisioned
applications. Carbon-based NMs are usually coated with metals, while metal-based
NMs are coated with natural organic compounds including chitosan, dextran,
alginate, or citric acid. On the other hand, the coating process is expected to
modify the surface properties of the NMs; several coating agents add negative or
positive charges to the particles, changing their interaction with the
environment. In this review, we analyze the most recent literature about coating
processes and the behavior of coated NMs in soil, water, and plants. In
particular, the behavior of the most commercialized metal-based NMs, such as
TiO2, ZnO, CeO2, CuO, Ag, and Au, and carbon-based NMs are discussed in this
review. The available articles about the effects of coated NMs in plants are
discussed. Up to now, there is no uniformity in the information to ensure that
the surface coverage increases or decreases the effects of NMs in plants. While
some parameters are increased, others are decreased. Since the data is
contradictory in some cases, the available literature does not allow researchers
to determine what concentrations benefit the plants. This review highlights
current results and future perspectives on the study of the effects of coated NMs
in the environment.
PMID- 29331810
TI - Behavior of Cylindrospermopsis raciborskii during coagulation and sludge storage
higher potential risk of toxin release than Microcystis aeruginosa?
AB - Owing to the global warming and its strong adaptability, Cylindrospermopsis
raciborskii has spread world-wide. However, as one of toxic cyanobacteria in many
drinking water sources, it has not been drawn proper consideration in drinking
water treatment plants so far. The investigation aimed at unveiling the fate of
C. raciborskii during polyaluminum ferric chloride (PAFC) coagulation and sludge
storage, revealing its differences from Microcystis aeruginosa. Results showed
that C. raciborskii cells were effectively removed intactly under optimum
coagulation conditions, but PAFC at higher dosages (>10 mg/L) triggered
additional cylindrospermopsins release. In sludge storage, coagulated C.
raciborskii cells suffered severe oxidative damage, leading to significant
cylindrospermopsins release after day 6. C. raciborskii manifested different
behaviors from M. aeruginosa which cells didn't release much microcystins during
coagulation and sludge storage. This was mostly due to their differences in
physiology and morphology. In flocs, M. aeruginosa could be enveloped by
coagulant which can protect cells against the nasty attack from outside, whereas
C. raciborskii with long filaments was hard to be wrapped and prone to suffering
oxidative damage. These results confirmed C. raciborskii had a higher risk of
toxin release in water production process than M. aeruginosa, which should
deserve more attention.
PMID- 29331808
TI - Simultaneous inhibition of hedgehog signaling and tumor proliferation remodels
stroma and enhances pancreatic cancer therapy.
AB - Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. It has
an excessive desmoplastic stroma that can limit the intratumoral delivery of
chemotherapy drugs, and protect tumor cells against radiotherapy. Therefore, both
stromal and tumor compartments need to be addressed in order to effectively treat
PDAC. We hereby co-deliver a sonic hedgehog inhibitor, cyclopamine (CPA), and a
cytotoxic chemotherapy drug paclitaxel (PTX) with a polymeric micelle formulation
(M-CPA/PTX). CPA can deplete the stroma-producing cancer-associated fibroblasts
(CAFs), while PTX can inhibit tumor proliferation. Here we show that in
clinically relevant PDAC models, M-CPA effectively modulates stroma by increasing
microvessel density, alleviating hypoxia, reducing matrix stiffness while
maintaining the tumor-restraining function of extracellular matrix. M-CPA/PTX
also significantly extends animal survival by suppressing tumor growth and
lowering the percentages of poorly to moderately differentiated tumor phenotypes.
Our study suggests that using multifunctional nanoparticles to simultaneously
target stromal and tumor compartments is a promising strategy for PDAC therapy.
PMID- 29331811
TI - Volatile organic compounds (VOCs) removal in non-thermal plasma double dielectric
barrier discharge reactor.
AB - Non-thermal plasma (NTP) an emerging technology to treat volatile organic
compounds (VOCs) present in unhygienic point source air streams. In present
study, double dielectric barrier discharge (DDBD) reactors were used for the
first time to evaluate the removal efficiency of VOCs mixture of different nature
at constant experimental conditions (input power 16-65.8 W, VOCs mixture feeding
rate 1-6 L/min, 100-101 ppm inlet concentration of individual VOC). Reactor A and
B with discharge gap at 6 mm and 3 mm respectively, were used in current study.
When treated at an input power of 53.7 W with gas feeding rate of 1 L/min in DDBD
reactor A, removal efficiency of the VOCs were: tetrachloroethylene (100%),
toluene (100%), trichloroethylene (100%), benzene (100%), ethyl acetate (100%)
and carbon disulfide (88.30%); whereas in reactor B, the removal efficiency of
all VOCs were 100%. Plasma-catalyst (Pt-Sn/Al2O3, BaTiO3 and HZSM-5) synergistic
effect on VOCs removal efficiency was also investigated. Highest removal
efficiency i.e 100% was observed for each compound with BaTiO3 and HZSM-5 at an
input power 65.8 W. However, integrating NTP with BaTiO3 and HZSM-5 leads to
enhanced removal performance of VOCs mixture with high activity, increase in
energy efficiency and suppression of unwanted byproducts.
PMID- 29331812
TI - Evidence of C--F-P and aromatic pi--F-P weak interactions in imidazolium ionic
liquids and its consequences.
AB - A simple change from alkyl group to alkene in side chain of imidazolium cation
with same anion resulted in a drastic impact on physical properties (e.g.,
melting point) from bmimPF6 IL to cmimPF6 IL. The underlying reasons have been
elucidated by structural and interaction studies with the help of DSC, SCXRD,
vibrational and multi-nuclear NMR spectroscopic techniques. Experiments reveal
existence of new weak interactions involving the carbon and pi cloud of the
imidazolium aromatic ring with fluoride of PF6 anion (i.e., C2--F-P and pi--F-P)
in cmimPF6 but are absent in structurally similar prototype IL, bmimPF6. Though
weak, these interactions helped to form ladder type supramolecular arrangement,
resulting in quite high melting point for cmimPF6 IL compared to bmimPF6 IL.
These findings emphasize that an IL system can behave uniquely because of the
existence of uncommon weak interactions.
PMID- 29331813
TI - Comparative study of the efficiency of computed univariate and multivariate
methods for the estimation of the binary mixture of clotrimazole and
dexamethasone using two different spectral regions.
AB - Three methods of analysis are conducted that need computational procedures by the
Matlab(r) software. The first is the univariate mean centering method which
eliminates the interfering signal of the one component at a selected wave length
leaving the amplitude measured to represent the component of interest only. The
other two multivariate methods named PLS and PCR depend on a large number of
variables that lead to extraction of the maximum amount of information required
to determine the component of interest in the presence of the other. Good
accurate and precise results are obtained from the three methods for determining
clotrimazole in the linearity range 1-12 MUg/mL and 75-550 MUg/mL with
dexamethasone acetate 2-20 MUg/mL in synthetic mixtures and pharmaceutical
formulation using two different spectral regions 205-240 nm and 233-278 nm. The
results obtained are compared statistically to each other and to the official
methods.
PMID- 29331814
TI - Characterization of sp3 bond content of carbon films deposited by high power gas
injection magnetron sputtering method by UV and VIS Raman spectroscopy.
AB - This paper presents the results of investigations of carbon films deposited by a
modified version of the magnetron sputtering method - HiPGIMS (High Power Gas
Injection Magnetron Sputtering). In this experiment, the magnetron system with
inversely polarized electrodes (sputtered cathode at ground potential and
positively biased, spatially separated anode) was used. This arrangement allowed
us to conduct the experiment using voltages ranging from 1 to 2kV and a power
supply system equipped with 25/50MUF capacitor battery. Carbon films were
investigated by VIS/UV Raman spectroscopy. Sp3/sp2 bonding ratio was evaluated
basing the elementary components of registered spectra. Our investigation showed
that sp3 bond content increases with discharge power but up to specific value
only. In extreme conditions of generating plasma impulses, we detected a reversed
relation of the sp3/sp2 ratio. In our opinion, a energy of plasma pulse favors
nucleation of a sp3 phase because of a relatively higher ionization state but in
extreme cases the influence of energy is reversed.
PMID- 29331815
TI - Chemometric simultaneous determination of Sofosbuvir and Ledipasvir in
pharmaceutical dosage form.
AB - Partial least squares (PLS), different families of continuous wavelet transform
(CWT), and first derivative spectrophotometry (DS) techniques were studied for
quantification of Sofosbuvir (SFB) and Ledipasvir (LDV) simultaneously without
separation step. The components were dissolved in Acetonitrile and the spectral
behaviors were evaluated in the range of 200 to 400nm. The ultraviolet (UV)
absorbance of LDV exhibits no interferences between 300 and 400nm and it was
decided to predict the LDV amount through the classic spectrophotometry (CS)
method in this spectral region as well. Data matrix of concentrations and
calibrated models were developed, and then by applying a validation set the
accuracy and precision of each model were studied. Actual concentrations versus
predicted concentrations plotted and good correlation coefficients by each method
resulted. Pharmaceutical dosage form was quantified by developed methods and the
results were compared with the High Performance Liquid Chromatography (HPLC)
reference method. Analysis Of Variance (ANOVA) in 95% confidence level showed no
significant differences among methods.
PMID- 29331816
TI - New robust sensitive fluorescence spectroscopy coupled with PLSR for estimation
of quercetin in Ziziphus mucronata and Ziziphus sativa.
AB - Flavonoids are natural antioxidants derived from plants and commonly found in a
variety of foods to sequester free radicals. Quercetin, belonging to flavonol
subclass of flavonoids, has received considerable attention because of its wide
uses as a nutritional supplement as well as a phytochemical remedy for a number
of diseases. In the current study, quantification of quercetin was carried out in
two medicinally important flavonoid rich plant Ziziphus mucronata and Ziziphus
sativa. Emission spectroscopy was utilized as a new method coupled with Partial
Least Squares Regression (PLSR) and the cross validation was done by UV-Visible
spectroscopy. The results indicated the higher quercetin content in Z. mucronata
(1.50+/-0.034%) than Z. sativa (1.21+/-0.052%), and were further verified through
Folin-Ciocalteu Colorimetric method (Z. mucronata; 1.41+/-0.26% and Z. sativa;
1.13+/-0.136%). In this study the sensitivity was explained in term of slope i.e.
Slope=0.9973.
PMID- 29331817
TI - Vapochromic behavior of MOF for selective sensing of ethanol.
AB - A MOF material, Co3[Co(CN)6]2 nanoparticles has been prepared for the effective
detection of ethanol in vapor phase. When exposed to ethanol vapor, the material
was changed from pink to purple, which is easily observed by naked eyes directly.
We propose that the ethanol response is due to ethanol molecules entering the
pores of the solid, where they alter the coordination geometry, leading to
conversion of their Co centers from octahedral to tetrahedral coordination.
Significantly, the change is reversible, which make the material reusable without
subjecting to dynamic vacuum or slightly warming.
PMID- 29331818
TI - The effect of CaO/SiO2 molar ratio of CaO-Al2O3-SiO2 glasses on their structure
and reactivity in alkali activated system.
AB - The influence of CaO/SiO2 molar ratio of calcium aluminosilicate glasses on
resulting structure and reactivity was investigated. Chemical compositions of
glasses were chosen to mimic the composition of the fly ash and slag amorphous
phase. Understanding the reactivity of these materials is of high importance
allowing further development of the composite cements to limit the environmental
footprint of cement industry. Fourier transform infrared spectroscopy (FTIR) and
Raman spectroscopy were employed to examine the structure of glasses. Reactivity
of the glasses was analyzed on paste samples after 1, 2, 7, 28 and 90days of
curing by means of thermogravimetry (TGA), X-ray diffraction (XRD) and FTIR.
Spectroscopic results emphasize dependence of the structure on the chemical
composition of the glasses. The higher CaO/SiO2 the more depolymerized the glass
network is, though there is no direct correlation with the reactivity.
Significant differences in reactivity is observed primarily between the glasses
of peraluminous (CaO/Al2O3<1) and percalcic region (CaO/Al2O3>1). Amongst the
pastes made of glasses of percalcic region a higher degree of reaction at later
ages is observed for the paste containing glass of lower CaO/SiO2 molar ratio.
This is due to both degree of depolimerization and the nature of these glasses
(pozzolanic and hydraulic materials). No difference of degree of reaction has
been observed within the glasses of CaO/SiO2 lower than 1.
PMID- 29331819
TI - New strategy for determination of anthocyanins, polyphenols and antioxidant
capacity of Brassica oleracea liquid extract using infrared spectroscopies and
multivariate regression.
AB - A new method was developed to determine the antioxidant properties of red cabbage
extract (Brassica oleracea) by mid (MID) and near (NIR) infrared spectroscopies
and partial least squares (PLS) regression. A 70% (v/v) ethanolic extract of red
cabbage was concentrated to 9 degrees Brix and further diluted (12 to 100%) in
water. The dilutions were used as external standards for the building of PLS
models. For the first time, this strategy was applied for building multivariate
regression models. Reference analyses and spectral data were obtained from
diluted extracts. The determinate properties were total and monomeric
anthocyanins, total polyphenols and antioxidant capacity by ABTS (2,2-azino-bis(3
ethyl-benzothiazoline-6-sulfonate)) and DPPH (2,2-diphenyl-1-picrylhydrazyl)
methods. Ordered predictors selection (OPS) and genetic algorithm (GA) were used
for feature selection before PLS regression (PLS-1). In addition, a PLS-2
regression was applied to all properties simultaneously. PLS-1 models provided
more predictive models than did PLS-2 regression. PLS-OPS and PLS-GA models
presented excellent prediction results with a correlation coefficient higher than
0.98. However, the best models were obtained using PLS and variable selection
with the OPS algorithm and the models based on NIR spectra were considered more
predictive for all properties. Then, these models provided a simple, rapid and
accurate method for determination of red cabbage extract antioxidant properties
and its suitability for use in the food industry.
PMID- 29331820
TI - Using vibrational molecular spectroscopy to reveal association of steam-flaking
induced carbohydrates molecular structural changes with grain fractionation,
biodigestion and biodegradation.
AB - Advanced vibrational molecular spectroscopy has been developed as a rapid and non
destructive tool to reveal intrinsic molecular structure conformation of
biological tissues. However, this technique has not been used to systematically
study flaking induced structure changes at a molecular level. The objective of
this study was to use vibrational molecular spectroscopy to reveal association
between steam flaking induced CHO molecular structural changes in relation to
grain CHO fractionation, predicted CHO biodegradation and biodigestion in
ruminant system. The Attenuate Total Reflectance Fourier-transform Vibrational
Molecular Spectroscopy (ATR-Ft/VMS) at SRP Key Lab of Molecular Structure and
Molecular Nutrition, Ministry of Agriculture Strategic Research Chair Program
(SRP, University of Saskatchewan) was applied in this study. The fractionation,
predicted biodegradation and biodigestion were evaluated using the Cornell Net
Carbohydrate Protein System. The results show that: (1) The steam flaking induced
significant changes in CHO subfractions, CHO biodegradation and biodigestion in
ruminant system. There were significant differences between non-processed (raw)
and steam flaked grain corn (P<.01); (2) The ATR-Ft/VMS molecular technique was
able to detect the processing induced CHO molecular structure changes; (3)
Induced CHO molecular structure spectral features are significantly correlated
(P<.05) to CHO subfractions, CHO biodegradation and biodigestion and could be
applied to potentially predict CHO biodegradation (R2=0.87, RSD=0.74, P<.01) and
intestinal digestible undegraded CHO (R2=0.87, RSD=0.24, P<.01). In summary, the
processing induced molecular CHO structure changes in grain corn could be
revealed by the ATR-Ft/VMS vibrational molecular spectroscopy. These molecular
structure changes in grain were potentially associated with CHO biodegradation
and biodigestion.
PMID- 29331821
TI - Influences of CdSe NCs on the photovoltaic parameters of BHJ organic solar cells.
AB - In this study, the high quality CdSe nanocrystals (NCs) capped with stearic acid
were synthesized in a solvent and then purified four times by using the
precipitation and redissolution process. The average size of the synthesized CdSe
NCs was determined ~3.0nm via transmission electron microscopy (TEM) measurement
and their corresponding optical band edge energy was also calculated as ~2.1eV
using ultraviolet-visible (UV-Vis) absorption spectroscopy. The bulk
heterojunction (BHJ) hybrid solar cells based on a ternary system including P3HT,
PCBM and CdSe NCs at different weight concentrations (0wt%, 0.1wt%, 0.5wt%, 1wt%
and 2wt%) were fabricated by spin-casting process. The effect of the
concentration of CdSe NCs on the photovoltaic parameters of these BHJ organic
solar cells was investigated. The surface morphology of the photoactive layer
modified by the incorporation of CdSe NCs into P3HT:PCBM matrix was observed with
scanning electron microscopy (SEM). It was shown that when the concentration of
CdSe NCs increases above 0.1wt% in this ternary system, the photovoltaic
performance of the devices significantly decreases. The power conversion
efficiency of the organic photovoltaic (OPV) device was enhanced ~20% by
incorporating CdSe NCs with 0.1wt% with respect to those without CdSe NCs.
PMID- 29331822
TI - Synthesis of UiO-66-OH zirconium metal-organic framework and its application for
selective extraction and trace determination of thorium in water samples by
spectrophotometry.
AB - In this study, a zirconium-based metal-organic framework (Zr-MOF), named UiO-66
OH, was synthesized by the solvo-thermal method and characterized by Fourier
transform-infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), and
scanning electron microscopy (SEM). This Zr-MOF was then employed as a sorbent
for selective extraction and preconcentration of thorium ions after their
complexation with 2-(2,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one (morin)
from environmental water samples prior to its spectrophotometrical determination.
The experimental parameters affecting extraction, such as pH of sample solution,
amount of Zr-MOF, type and volume of eluting solvent, adsorption and desorption
time, and concentration of complexing agent were evaluated and optimized. Under
the optimized conditions, an enrichment factor of 250 was achieved. The limit of
detection was calculated to be 0.35MUg.L-1 with a linear range between 10 and
2000MUg.L-1of thorium. The maximum sorption capacity of MOF toward thorium was
found to be 47.5mg.g-1. The proposed procedure was successfully applied to the
analysis of real water samples.
PMID- 29331823
TI - Pre-pregnancy maternal depressive symptoms and low birth weight and preterm birth
outcomes: Assessment of adolescent background characteristics and birth outcomes
in adulthood.
AB - PURPOSE: In the United States and other countries of the world , high prevalence
of pre-pregnancy depressive symptoms and depression during pregnancy is an
important public health concern, as they are associated with low birth weight
(LBW) and preterm birth (PTB) outcomes in adulthood. However, the relationships
among pre-pregnancy depressive symptoms, low birth weight, preterm birth outcomes
and household characteristics have not been well established. METHODS: The study
used data from 7120 adolescent female participants in the National Longitudinal
Study of Adolescent to Adult Health data from Waves I (1994-1995 in-school
interview), II (1996 as in-home), III (2001-2002 as in-home interview), IV (2008
as in-home interview) and Wave V is currently underway. The main outcomes were
LBW and PTB. Maternal depressive symptoms were assessed with the Center for
Epidemiologic Studies Depression scale (CES-D) using a cut-off point of 24 to
indicate higher depressive symptoms . Odds ratios were used as an estimate of the
relative risk using generalized estimating equations (GEE). RESULTS: In Wave I,
prevalence of depressive symptoms among age groups 11-15 (54.1%) was higher than
older adolescents (45.9%) were. With the exception of depressive symptoms
reported in Wave II, respondents reporting depressive symptoms in Waves I and III
had similar unadjusted rates of LBW or PTB infants in adulthood. Mothers
reporting higher depressive symptoms in older adolescence (15-19 years) had
elevated odds of LBW infants (3.58 [95% CI=1.81, 7.09]) in Wave III compared with
others reporting low depressive symptoms. CONCLUSIONS: Undeniably, childhood
socioeconomic circumstances are important determinants of disease risks and
improved health functioning and in particular birth outcomes in adulthood. Since
poorer households have fewer resources to cope with stressful events that
generate mood and other depressive symptoms over the life course, findings of
research suggest treating depressive symptoms prior to pregnancy will yield
significant dividends for mothers and society. Furthermore, without careful
control of household contexts, the association between depressive symptoms and
birth outcomes is likely to be confounded.
PMID- 29331824
TI - Effects of subject-case marking on agreement processing: ERP evidence from
Basque.
AB - Previous cross-linguistic research has found that comprehenders are immediately
sensitive to various kinds of agreement violations across languages. We focused
on Basque, a verb-final ergative language with both subject-verb (SV) and object
verb (OV) agreement. We compared the effects of SV agreement violations on
comprehenders' event-related brain potentials (ERPs) in transitive sentences
(where OV agreement is present, and the subject is ergative) and intransitive
sentences (where OV agreement is absent, and the subject is absolutive). We
observed a P600 effect in both cases, but only violations with intransitive
subjects elicited an early posterior negativity. Such a qualitative difference
suggests that distinct neurocognitive mechanisms are involved in processing
agreement with transitive subjects (which are marked with ergative case) versus
intransitive subjects (which bear absolutive case). Building on theoretical
proposals that in languages such as Basque, true agreement occurs with absolutive
subjects but not with ergative subjects, we submit that the early posterior
negativity may be an electrophysiological signature for true agreement.
PMID- 29331825
TI - A novel strategy for the efficient removal of toxic cyanate by the combinatorial
use of recombinant enzymes immobilized on aminosilane modified magnetic
nanoparticles.
AB - Cyanase detoxifies cyanate by transforming it to ammonia and carbon dioxide in a
bicarbonate-dependent reaction, however, dependence on bicarbonate limits its
utilization in large-scale applications. A novel strategy was therefore developed
for overcoming this bottleneck by the combined application of cyanase (rTl-Cyn)
and carbonic anhydrase (rTl-CA). The synergistic effect of rTl-Cyn and rTl-CA
could reduce the dependence of bicarbonate by 80%, compared to using rTl-Cyn
alone. Complete degradation of cyanate (4 mM) was achieved with buffered
conditions and 85 +/- 5% degradation with industrial wastewater sample, when 20 U
of rTl-Cyn was applied. Furthermore, a similar percentage of degradation was
achieved using 80% less bicarbonate, when rTl-Cyn and rTl-CA were used together
under identical conditions. In addition, rTl-Cyn and rTl-CA were immobilized onto
the magnetic nanoparticles and their catalytic activity, stability and
reusability were also evaluated. This is the first report on the synergistic
biocatalysis by rTl-Cyn and rTl-CA, for cyanate detoxification.
PMID- 29331826
TI - Pathway and mechanism of nitrogen transformation during composting: Functional
enzymes and genes under different concentrations of PVP-AgNPs.
AB - Polyvinylpyrrolidone coated silver nanoparticles (PVP-AgNPs) were applied at
different concentrations to reduce total nitrogen (TN) losses and the mechanisms
of nitrogen bio-transformation were investigated in terms of the nitrogen
functional enzymes and genes. Results showed that mineral N in pile 3 which was
treated with AgNPs at a concentration of 10 mg/kg compost was the highest (6.58
g/kg dry weight (DW) compost) and the TN loss (47.07%) was the lowest at the end
of composting. Correlation analysis indicated that TN loss was significantly
correlated with amoA abundance. High throughput sequencing showed that the
dominant family of ammonia-oxidizing bacteria (AOB) was Nitrosomonadaceae, and
the number of Operational Taxonomic Units (OTUs) reduced after the beginning of
composting when compared with day 1. In summary, treatment with AgNPs at a
concentration of 10 mg/kg compost was considerable to reduce TN losses and
reserve more mineral N during composting.
PMID- 29331827
TI - Pilot-scale outdoor photobioreactor culture of the marine dinoflagellate
Karlodinium veneficum: Production of a karlotoxins-rich extract.
AB - A pilot-scale bioprocess was developed for the production of karlotoxin-enriched
extracts of the marine algal dinoflagellate Karlodinium veneficum. A bubble
column and a flat-panel photobioreactors (80-281 L) were used for comparative
assessment of growth. Flow hydrodynamics and energy dissipation rates (EDR) in
the bioreactors were characterized through robust computational fluid dynamic
simulations. All cultures were conducted monoseptically outdoors. Bubble column
(maximum cell productivity in semicontinuous operation of 58 * 103 cell mL-1 day
1) proved to be a better culture system for this alga. In both reactors, the
local EDR near the headspace, and in the sparger zone, were more than one order
of magnitude higher than the average value in the whole reactor (=4 * 10-3 W kg
1). Extraction of the culture and further purification resulted in the desired
KTXs extracts. Apparently, the alga produced three congeners KTXs: KmTx-10 and
its sulfated derivative (sulfo-KmTx-10) and KmTx-12. All congeners possessed
hemolytic activity.
PMID- 29331828
TI - A recovery time after warming restores mitochondrial function and improves
developmental competence of vitrified ovine oocytes.
AB - The aim of the present study was to assess the ability of vitrified/warmed oocyte
to recover from vitrification-induced damages after warming. In vitro matured,
vitrified/warmed ovine oocytes were assessed for developmental competence,
mitochondrial activity and distribution, ATP, ROS and catalase levels during 6 h
of in vitro culture using fresh oocytes as control. ATP content in vitrified
oocytes was lower than control during 4 h of post warming culture (p < .01).
Vitrified oocytes were able to fill this gap only after 6 h of post-warming
incubation. Moreover, mitochondrial activity was significantly lower (p < 0.01)
in vitrified oocytes compared to controls, and this difference was maintained up
to 2 h of incubation. Then the activity increased and at 4 h it was higher
compared to controls (p < 0.01). These oocytes showed an increasing rate of
clustered distribution of mitochondria which was lower than controls during the
first 4 h of post warming culture (p < 0.01). ROS level was significantly higher
at 0 h in vitrified compared to control oocytes and this difference was
maintained also at 2 h and 6 h of incubation (p < 0.01). Catalase level was
higher in vitrified oocytes than controls (p < 0.01) during the entire culture
period. Cleavage and blastocyst rates were lower in vitrified oocytes compared to
control ones during the two first time point of incubation period (p < .01),
indeed they increased significantly from 0 to 4 h of incubation post warming (p <
0.01). The study demonstrated that vitrified/warmed oocytes need an extra time to
restore damage due to cryopreservation procedures and to increase their
developmental potential. Thus, time of damage recovery after vitrification could
be used to standardize the vitrification protocols and to improve the
developmental competence of vitrified/warmed oocytes.
PMID- 29331829
TI - Additional small dose of prostaglandin F2alpha at timed artificial insemination
failed to improve pregnancy risk of lactating dairy cows.
AB - Two experiments were performed to test the hypothesis that administering
PGF2alpha concurrent with timed artificial insemination (AI) in lactating dairy
cows would enhance pregnancy per AI (P/AI). In experiment 1, lactating Holstein
cows (n = 289) in one herd were enrolled after a non-pregnancy diagnosis (30-36 d
after AI) to synchronize subsequent ovulation before AI. Cows were assigned
randomly to receive (im) 10 mg of PGF2alpha concurrent with timed AI (Day 0;
treatment) or no injection (control). Blood samples were collected on Days -3, 0,
and 13 to determine serum concentrations of progesterone. Ovaries were scanned
via transrectal ultrasonography to determine follicle diameters (Day -3),
subsequent ovulation risk (Day 13), and total volume of luteal tissue (Day 13).
Diagnosis of pregnancy occurred on Days 32 and 80 after AI. Ovulation risk post
AI exceeded 90% and did not differ between treatments. In addition, PGF2alpha
treatment only numerically increased progesterone (5.7 +/- 0.3 vs. 6.2 +/- 0.3
ng/mL) or luteal tissue volume (8.9 +/- 0.4 vs. 9.8 +/- 0.5 ng/mL) on Day 13 by
8.8% (P = .206) or 10.1% (P = .134) in control and treated cows, respectively.
Pregnancy per AI at Days 32 (P = .50) and 80 (P = .33) did not differ between
treatments. Cows with progesterone >0.5 ng/mL at timed AI had reduced (P < .001)
ovulation risk but risk was unaffected by treatment. In experiment 2, lactating
dairy cows (n = 1828) in two commercial dairy herds were enrolled at time of
insemination (Day 0), and assigned randomly to treatment or control as described
in experiment 1. Initial (Days 32-35) and confirmed (Days 63-68) pregnancy
diagnosis revealed no differences in P/AI or pregnancy loss. Pregnancy diagnosis
on Days 32-35 produced percentage increases in P/AI for primiparous compared with
multiparous cows (20.8%; P = .002), for first-service compared with repeat
service cows (26%; P = .001), and cows in one herd compared with the second herd
(36%; P < .001). Pregnancy loss was greater (P = .001) for cows inseminated at
first (10.0%) vs. later services (5.3%) but was unaffected by treatment. Cows
treated with PGF2alpha in one herd produced more twins than control cows (11.7
vs. 3.2%), whereas no treatment difference was detected in the second herd (5.6
vs. 5.6%), respectively. We conclude that im treatment of lactating dairy cows
with 10 mg of PGF2alpha concurrent with timed AI did not improve P/AI or embryo
survival, but increased twinning in one herd.
PMID- 29331830
TI - Fetal development of the Poeppig's woolly monkey (Lagothrix poeppigii).
AB - The intrauterine development is an evolutionary strategy that prepares the
neonate for extra-uterine life, thus providing important information on the life
history of species. In this study, we described the external and internal
morphology of 25 fetuses of Poeppig's woolly monkeys (Lagothrix poeppigii) by
taking advantage of a 10-year participatory collection of biological samples
originated from animals hunted for subsistence purposes in the Peruvian Amazon.
Logistic regressions estimated the probability of occurrence of each external
morphological characteristic in relation to the crown-rump length (CRL). The
presence of nails, closed eyelids, differentiated genitalia and formed limbs with
separation of the digits were observed in all analyzed fetuses (>=4.2 cm CRL).
The other characteristics appeared in the following order: skin with epidermal
pigmentation, oral and nasal mucosal pigmentation, tactile pelage and covering
pelage. Although advanced fetuses (>15.8 cm CRL) showed most fetal external
characteristics, they were not fully developed and no specimen showed tooth
eruption or opened eyelids. The growth formula used to determine fetal age was ?W
= 0.042 (t - 45), with a high linear relationship between CRL and gestational
age. All associations between the external biometry, absolute volume of internal
organs and the CRL had a high coefficient of determination. Advanced fetuses and
adults showed similar relative volume of thoracic and abdominal organs, except
for thymus and the liver with a higher and lower relative volume, respectively.
The relative volume of the tubular gastrointestinal tract and the thymus had a
constant increase along fetal development, and the liver showed a significant
decrease. This study describes important morphological events for understanding
the gestational development in the Lagothrix genus. In addition, these results
may be useful to improve imaging techniques, contributing to the in situ and ex
situ reproductive management of this highly hunted species in the Amazon.
PMID- 29331831
TI - Effect of bone morphogenetic proteins 2 and 4 on survival and development of
bovine secondary follicles cultured in vitro.
AB - This study evaluated the effect of bone morphogenetic proteins 2 (BMP2) and 4
(BMP2) on follicle development and mRNA expression for GDF9, Cyclin B1, BMPR1A,
BMPR1B, BMPRII, FSHR and SMAD1 in bovine secondary follicles cultured in vitro.
Isolated secondary follicles were cultured for 18 days in TCM199+ medium alone or
supplemented with BMP2 (10 ng/mL), BMP4 (100 ng/mL) or combination of both BMP2
and 4. Real-time PCR was used to analyze mRNA levels in fresh and cultured
follicles. After 18 days of culture, follicles cultured with BMP2 alone or with
BMP4 alone had larger diameters when compared to control (P < .05). In addition,
all treatments promoted antrum formation and maintained a high viability rate
through the growing period. The presence of BMP2, BMP4 or both together did not
influence mRNA expression for the tested genes. However, the in vitro culture
induces down-regulation for mRNA expression of BMPR1A. In conclusion, the
addition of BMP2 or BMP4 alone in cultured medium promotes follicular growth and
antrum formation in bovine follicles after 18 days of in vitro culture.
PMID- 29331832
TI - Investigations on a cryopreservation protocol for long-term storage of psittacine
spermatozoa using cockatiel semen as an example.
AB - The aim of the present study was the establishment of an effective protocol for
cryopreservation of psittacine semen. Therefore, pooled semen samples of 30
cockatiels (Nymphicus hollandicus) were diluted with modified Lake diluent (1:4),
partitioned into four equal parts. Three portions were mixed with three
cryoprotectants (dimethylacetamide, dimethyl sulfoxide, glycerol) in 4%, 8% and
12% final concentration, respectively, whereas the 4rth part served as control.
Altogether, 96 incremental diluted semen samples were obtained for investigation.
Each cryoprotective agent (CPA) in each final concentration was evaluated
regarding sperm motility immediately after dilution and another four times every
30 min. Sperm viability was evaluated 0 and 120 min after dilution using the
fluorescence stain SYBR(r) Green/propidium iodide. Sperm morphology was evaluated
0 and 120 min after dilution using eosin B stains. Glycerol demonstrated a lethal
effect on cockatiel spermatozoa in all concentrations, whereas dimethylacetamide
(DMA) in 8% final concentration proved to have the least adverse effect on semen
parameters. Comparison of quick and slow freezing methods using DMA 8% revealed
significantly higher rates of viable and motile spermatozoa after computer
controlled rate freezing. Two insemination experiments resulted in an egg
fertility rate of 92.59% and 67.65% after artificial insemination with freshly
collected semen samples, compared to 30.77% and 18.00% egg fertility rates using
frozen/thawed semen. Altogether, 12 chicks hatched out of eggs inseminated with
cryopreserved semen. To our knowledge, this is the first time for cockatiels to
be successfully reproduced after artificial insemination using cryopreserved
semen.
PMID- 29331833
TI - Potential factors that impact the radon level and the prediction of ambient dose
equivalent rates of indoor microenvironments.
AB - This study aimed to measure the equilibrium equivalent radon (EECRn)
concentration in an old building (Building-1) and a new building (Building-2)
with mechanical ventilation and a natural ventilation system, respectively. Both
buildings were located at the campus of University Kebangsaan Malaysia. The
concentration of indoor radon was measured at 25 sampling stations using a radon
detector model DOSEman PRO. The sampling was conducted for 8 h to represent daily
working hours. A correlation of the radon concentration was made with the annual
inhalation dose of the occupants at the indoor stations. The equilibrium factor
and the annual effective dose on the lung cancer risks of each occupant were
calculated at each sampling station. The average equilibrium equivalent radon
measured in Building-1 and Building-2 was 2.33 +/- 0.99 and 3.17 +/- 1.74 Bqm-3,
respectively. The equilibrium factor for Building 1 ranged from 0.1053 to 0.2273,
and it ranged from 0.1031 to 0.16 for Building 2. The average annual inhalation
doses recorded at Building-1 and Building-2 were 0.014 +/- 0.005 mSv y-1 and
0.020 +/- 0.013 mSv y-1, respectively. The annual effective dose for Building-1
was 0.034 +/- 0.012 mSv y-1, and it was 0.048 +/- 0.031 mSv y-1 for Building-2.
The values of equilibrium equivalent radon concentration for both buildings were
below the standard recommended by the International Commission on Radiological
Protection (ICRP). However, people may have different radon tolerance levels.
Therefore, the inhalation of the radon concentration can pose a deleterious
health effect for people in an indoor environment.
PMID- 29331834
TI - Land-Water-Food Nexus and indications of crop adjustment for water shortage
solution.
AB - While agriculture places the greatest demand on water resources, increasing
agricultural production is worsening a global water shortage. Reducing the
cultivation of water-consuming crops may be the most effective way to reduce
agricultural water use. However, when also taking food demand into consideration,
sustaining the balance between regional water and food securities is a growing
challenge. This paper addresses this task for regions where water is
unsustainable for food production (Beijing-Tianjin-Hebei Region for example) by:
(i) assessing the different effects of wheat and maize on water use; (ii)
analyzing virtual water and virtual land flows associated with food imports and
exports between Beijing-Tianjin-Hebei and elsewhere in China; (iii) identifying
sub-regions where grain is produced using scarce water resources but exported to
other regions; and (iv) analyzing the potentiality for mitigating water shortage
via Land-Water-Food Nexus. In the Beijing-Tianjin-Hebei Region, the study reveals
that 29.76 bn m3 of virtual water (10.81 bn m3 of blue virtual water) are used by
wheat and maize production and 8.77 bn m3 of virtual water used in nearly 2
million ha of cropland to overproduce 12 million ton of maize for external food
consumption. As an importing-based sub-region with high population density,
Beijing & Tianjin imported mostly grain (wheat and maize) from Shandong Province.
Then, Hebei Province, as an exporting-based sub-region with severe water
shortage, overproduced too much grain for other regions, which aggravated the
water crisis. To achieve an integrated and sustainable development of the Beijing
Tianjin-Hebei Region, Hebei Province should stop undertaking the breadbasket role
for Beijing & Tianjin and pay more attention to groundwater depletion. The
analysis of the Land-Water-Food Nexus indicates how shifts in cultivated crops
can potentially solve the overuse of water resources without adverse effects on
food supply. It also provides meaningful information to support policy decisions
about regional cropping strategies.
PMID- 29331835
TI - Integrating priority areas and ecological corridors into national network for
conservation planning in China.
AB - Considering that urban expansion and increase of human activities represent
important threats to biodiversity and ecological processes in short and long
term, developing protected area (PA) network with high connectivity is considered
as a valuable conservation strategy. However, conservation planning associated
with the large-scale network in China involves important information loopholes
about the land cover and landscape connectivity. In this paper, we made an
integrative analysis for the identification of conservation priority areas and
least-cost ecological corridors (ECs) in order to promote a more representative,
connected and efficient ecological PA network for this country. First, we used
Zonation, a spatial prioritization software, to achieve a hierarchical mask and
selected the top priority conservation areas. Second, we identified optimal
linkages between two patches as corridors based on least-cost path algorithm.
Finally, we proposed a new framework of China's PA network composed of
conservation priority and ECs in consideration of high connectivity between
areas. We observed that priority areas identified here cover 12.9% of the region,
distributed mainly in mountainous and plateau areas, and only reflect a spatial
mismatch of 19% with the current China's nature reserves locations. From the
perspective of conservation, our result provide the need to consider new PA
categories, specially located in the south (e.g., the middle-lower Yangtze River
area, Nanling and Min-Zhe-Gan Mountains) and north regions (e.g., Changbai
Mountains), in order to construct an optimal and connected national network in
China. This information allows us better opportunities to identify the relative
high-quality patches and draft the best conservation plan for the China's
biodiversity in the long-term run.
PMID- 29331836
TI - Effects of ZnO nanoparticles in the Caspian roach (Rutilus rutilus caspicus).
AB - Most studies investigating the toxicity of zinc oxide nanoparticles (ZnO NPs)
focused on the effect of size, whereas exposure concentration and duration
remained poorly understood. In this study, the effect of acute and sub-acute
exposures of ZnO NPs on Zn compartmentalization and biomarkers' expression were
investigated in Rutilus rutilus caspicus (Caspian roach) considering various
exposure scenarios: i) the assessment of the concentration-response curves and
median lethal concentration (LC50); ii) the assessment of the effects of
organisms exposed at LC50 value and one tenth of LC50 value of ZnO NPs
suspensions for 4 d and 28 d, respectively; iii) the assessment of 14 d
depuration period. The same concentrations of ZnSO4 were investigated. The
highest Zn accumulation was detected in gill after sub-acute exposure (4.8 mg/L;
28 d) followed by liver, kidney and muscle. In gill, liver and muscle, Zn from Zn
NPs accumulated higher concentrations. Depuration (14 d) decreased Zn content in
each organ, but no complete removal occurred except for muscle. Biomarkers'
activity was significantly over expressed after treatments, but depuration
brought back their values to background levels and most effects were related to
acute concentrations (48 mg/L; 4 d) and in presence of ZnSO4. Histopathological
analyses showed that the exposure to ZnO NPs increased lesions in gill, liver and
kidney, with a direct proportionality between alterations and Zn accumulated in
the target organs. After depuration, lesions regressed for both ZnO NPs and
ZnSO4, but not in a complete way. These data could contribute to increase the
knowledge about ZnO NPs risk assessment in aquatic vertebrates, suggesting that
the size of ZnO NPs can influence biomarker and histopathological effects.
PMID- 29331837
TI - Spontaneous focusing on numerosity in preschool as a predictor of mathematical
skills and knowledge in the fifth grade.
AB - Previous studies in a variety of countries have shown that there are substantial
individual differences in children's spontaneous focusing on numerosity (SFON),
and these differences are positively related to the development of early
numerical skills in preschool and primary school. A total of 74 5-year-olds
participated in a 7-year follow-up study, in which we explored whether SFON
measured with very small numerosities at 5 years of age predicts mathematical
skills and knowledge, math motivation, and reading in fifth grade at 11 years of
age. Results show that preschool SFON is a unique predictor of arithmetic fluency
and number line estimation but not of rational number knowledge, mathematical
achievement, math motivation, or reading. These results hold even after taking
into account age, IQ, working memory, digit naming, and cardinality skills. The
results of the current study further the understanding of how preschool SFON
tendency plays a role in the development of different formal mathematical skills
over an extended period of time.
PMID- 29331838
TI - Association of CAST2, HSP90AA1, DNAJA1 and HSPB1 genes with meat tenderness in
Nellore cattle.
AB - The objective of this study was to evaluate the association of expression of
CAPN1, CAPN2, CAST, HSP90AA1, DNAJA1 and HSPB1 genes with meat tenderness in
Nellore cattle. Three experimental groups were selected by shear force (SF):
moderately tender (SF=34.3+/-5.8N), moderately tough (SF=56.8+/-7.8N), and very
tough meat (SF=80.4+/-15N). Gene expression was evaluated by real-time PCR.
Expression of the CAPN1, CAPN2, CAST and CAST1 genes did not differ between
groups. Expression of the CAST2 was up-regulated (P<0.05) in the moderately tough
and very tough meat groups. Down-regulation of the HSP90AA1, DNAJA1 and HSPB1
genes (P<0.05) was observed in the moderately tender meat group. The present
results suggest that meat tenderness in Nellore cattle does not directly depend
on the expression of the CAPN1 and CAPN2 genes, but is associated with the
expression of other genes such as CAST2, HSP90AA1, DNAJA1 and HSPB1.
PMID- 29331839
TI - Functional characterization of a novel hERG variant in a family with recurrent
sudden infant death syndrome: Retracting a genetic diagnosis.
AB - Long QT syndrome (LQTS) is the most common cardiac ion channelopathy and has been
found to be responsible for approximately 10% of sudden infant death syndrome
(SIDS) cases. Despite increasing use of broad panels and now whole exome
sequencing (WES) in the investigation of SIDS, the probability of identifying a
pathogenic mutation in a SIDS victim is low. We report a family-based study who
are afflicted by recurrent SIDS in which several members harbor a variant,
p.Pro963Thr, in the C-terminal region of the human-ether-a-go-go (hERG) gene,
published to be responsible for cases of LQTS type 2. Functional characterization
was undertaken due to the variable phenotype in carriers, the discrepancy with
published cases, and the importance of identifying a cause for recurrent deaths
in a single family. Studies of the mutated ion channel in in vitro heterologous
expression systems revealed that the mutation has no detectable impact on
membrane surface expression, biophysical gating properties such as activation,
deactivation and inactivation, or the amplitude of the protective current
conducted by hERG channels during early repolarization. These observations
suggest that the p.Pro963Thr mutation is not a monogenic disease-causing LQTS
mutation despite evidence of co-segregation in two siblings affected by SIDS. Our
findings demonstrate some of the potential pitfalls in post-mortem molecular
testing and the importance of functional testing of gene variants in determining
disease-causation, especially where the impacts of cascade screening can affect
multiple generations.
PMID- 29331840
TI - Post mortem vitreous magnesium in adult population.
AB - BACKGROUND: The study of post mortem vitreous magnesium (Mg) is less common than
sodium (Na), chloride (Cl) and potassium (K) in the forensic literature. There is
no accepted normal range for post mortem vitreous Mg and the relationship between
post mortem vitreous Mg levels and post mortem interval (PMI), other electrolyte
levels, disease conditions, age and sex have not been fully established. AIM: To
investigate the relationship of post mortem vitreous Mg with age, sex, PMI,
vitreous electrolyte levels and diabetic status. METHODS: A retrospective study
of 20 consecutive cases of diabetics and 20 non-diabetic adult deaths was
performed. Spearman correlation and the permutation test were used to explore the
relationship between post mortem vitreous Mg and continuous and categorical
variables respectively. RESULTS: The mean post mortem vitreous Mg was 1.03mmol/L
(95%CI: 0.98-1.08mmol/L). The absolute Spearman correlation coefficients (rho)
between post mortem vitreous Mg with PMI, age, and other vitreous electrolytes
(Na, Cl, and K) ranged between 0.04-0.21 (p>0.19). Post mortem vitreous Mg was
statistically higher in diabetics (mean difference: 0.08mmol/L; area-under-the
curve=0.65 on receiver-operator-characteristic curve). No statistical difference
was demonstrated between sexes (p=0.92). CONCLUSIONS: In our adult population,
post mortem vitreous Mg did not correlate with age, PMI, other vitreous
electrolytes (sodium, chloride and potassium) or sex. It was higher in diabetics,
however had limited utility as a surrogate marker. Overall, post mortem Mg is
steady in the early post mortem period with a mean of 1.03mmol/L.
PMID- 29331841
TI - Culture beats gender? The importance of controlling for identity- and parenting
related risk factors in adolescent psychopathology.
AB - This study analyzed the unique effects of gender and culture on psychopathology
in adolescents from seven countries after controlling for factors which might
have contributed to variations in psychopathology. In a sample 2259 adolescents
(M = 15 years; 54% female) from France, Germany, Turkey, Greece, Peru, Pakistan,
and Poland identity stress, coping with identity stress, maternal parenting
(support, psychological control, anxious rearing) and psychopathology
(internalizing, externalizing and total symptomatology) were assessed. Due to
variations in stress perception, coping style and maternal behavior, these
covariates were partialed out before the psychopathology scores were subjected to
analyses of variance with gender and country as factors. These analyses leveled
out the main effect of country and revealed country-specific gender effects. In
four countries, males reported higher internalizing and total symptomatology than
females. Partialing out the covariates resulted in a clearer picture of culture
specific and gender-dependent effects on psychopathology, which is helpful in
designing interventions.
PMID- 29331842
TI - Predicting 1-year disability and mortality of injured older adults.
AB - PURPOSE: The growing incidence of elderly patients injured from falls, combined
with a growing understanding of the contribution of cognition and frailty to
mortality, prompted this work. Our objective was to develop a clinical risk
prediction model for prognosticating disability and mortality among injured older
adults 1 year after hospitalization. METHODS: Secondary analysis of prospective
longitudinal data from an urban Level 1 trauma center. A proportional odds
regression model was used to model mortality and functional status as ordinal
outcomes. Death was treated as the lowest functional status, and 3 ordered groups
of the Barthel Index were treated as higher functional status. 188 patients aged
65 and older who were admitted through the emergency department from 2013 to 2014
with a primary injury diagnosis comprised the prospective cohort. Follow-up
assessments were performed at 30-days, 90-days, 6-months, and 1-year. Predictors
in the model included: baseline physical function, baseline cognition, two
physical frailty measures, age, injury severity, a comorbidity index, gender,
living location, mechanism of injury, and hospital admitting service. RESULTS:
The full model yielded an R2 of 0.45, and Life Space Assessment, Vulnerable
Elders Survey, and Injury Severity were the most influential predictors.
Approximated models (to encourage clinical use) yielded an R2 of 0.86.
Calibration assessment (i.e., accuracy) demonstrated a mean squared error <0.003
at all 3 intercepts. CONCLUSIONS: A moderate statistical signal was discovered
that contributed to a highly accurate clinical prediction model. Approximated
models and nomograms could be used by clinicians, patients, and families in
shared decision making during hospitalization.
PMID- 29331843
TI - Performance of genotypic algorithms for predicting tropism for HIV-1 CRF01_AE
recombinant.
AB - OBJECTIVES: There is no consensus about the performances of genotypic rules for
predicting HIV-1 non-B subtype tropism. Three genotypic methods were compared for
CRF01_AE HIV-1 tropism determination. METHODS: The V3 env region of 207 HIV-1
CRF01_AE and 178 B subtypes from 17 centers in France and 1 center in Switzerland
was sequenced. Tropism was determined by Geno2Pheno algorithm with false positive
rate (FPR) 5% or 10%, the 11/25 rule or the combined criteria of the 11/25, net
charge rule and NXT/S mutations. RESULTS: Overall, 72.5%, 59.4%, 86.0%, 90.8% of
the 207 HIV-1 CRF01_AE were R5-tropic viruses determined by Geno2pheno FPR5%,
Geno2pheno FPR10%, the combined criteria and the 11/25 rule, respectively. A
concordance of 82.6% was observed between Geno2pheno FPR5% and the combined
criteria for CRF01_AE. The results were nearly similar for the comparison between
Geno2pheno FPR5% and the 11/25 rule. More mismatches were observed when
Geno2pheno was used with the FPR10%. Neither HIV viral load, nor current or nadir
CD4 was associated with the discordance rate between the different algorithms.
CONCLUSION: Geno2pheno predicted more X4-tropic viruses for this set of CRF01_AE
sequences than the combined criteria or the 11/25 rule alone. For a conservative
approach, Geno2pheno FPR5% seems to be a good compromise to predict CRF01_AE
tropism.
PMID- 29331844
TI - Assessing the risk of CMV reactivation and reconstitution of antiviral immune
response post bone marrow transplantation by the QuantiFERON-CMV-assay and real
time PCR.
AB - BACKGROUND: CMV reactivation is a major cause of severe complications in
allogeneic hematopoietic stem cell transplant (HSCT) recipients. The risk of CMV
reactivation depends on the serostatus (+/-) of the donor (D) and recipient (R).
The reconstitution of CMV-specific T-cell responses after transplantation is
crucial for the control of CMV reactivation. OBJECTIVES: The study aimed to
determine the cellular immune status correlating with protection from high-level
CMV viremia (>5000 copies/ml) and disease. STUDY DESIGN: We monitored CMV
specific cellular immune responses in 9 high-risk (D-/R+), 14 intermediate risk
(D+/R+) and 3 low risk individuals (D+/R-), and 8 CMV negative controls (D-/R-).
Interferon- gamma (IFN-gamma) levels as a marker for the CD8+ T-cell response
were determined by the QuantiFERON-CMV-assay and compared to viral loads
determined by PCR. RESULTS: Early CMV reactivation was detected in all high-risk
and 13/14 intermediate risk individuals. High-level viremia was detected in 5/7
high and 7/14 intermediate risk patients. Reconstitution of the CMV-specific
cellular immune response started from 3 months after transplantation and resulted
in protection against CMV reactivation. Re-establishing of CMV-specific T-cell
immune responses with IFN- gamma levels >8.9 IU/ml is crucial for protection from
high-level CMV viremia. CONCLUSIONS: Monitoring of HSCT-recipients with the
QuantiFERON-CMV-assay might be of great benefit to optimize antiviral treatment.
PMID- 29331845
TI - Effect of levetiracetam on extracellular amino acid levels in the dorsal
hippocampus of rats with temporal lobe epilepsy.
AB - Levetiracetam (LEV) is an anticonvulsant drug with a unique mechanism of action
that is not completely understood. However, its activity profile may involve
effects on excitatory and/or inhibitory neurotransmission since the primary
target of LEV, synaptic vesicle protein 2A, is ubiquitously expressed in all
types of synaptic vesicles. Therefore, the objective of the present study was to
explore the effect of LEV (300 mg/kg/day for one week, administered via osmotic
mini-pumps) on neurotransmitter release and its probable selective effect on
extracellular gamma-amino butyric acid (GABA), glutamate (Glu), aspartate (Asp),
glutamine (Gln), taurine (Tau) and glycine (Gly) concentrations (using in vivo
microdialysis under basal and high-K+ conditions) in the dorsal hippocampus (DH),
a region that undergoes major synaptic changes during epilepsy. Epileptic rats
developed clear signs of hyperexcitability, i.e., an elevated Glu/GABA ratio in
the DH. The LEV concentration in blood after 7 days of treatment was within the
therapeutic range. In contrast, LEV was not detected four days after mini-pump
removal (washout period). Furthermore, LEV restored the Glu/GABA ratio to
approximately the control level and significantly increased the GABA
concentration after the initiation of high-K+ conditions. Based on these data,
LEV treatment restored the lost balance between the excitatory and inhibitory
systems under basal conditions. Moreover, LEV showed a selective effect by
preferentially increasing vesicular release of GABA, a mechanism by which LEV
could reduce epileptic seizures.
PMID- 29331846
TI - Functional neuroimaging in Rasmussen syndrome.
AB - PURPOSE: For a diagnosis of Rasmussen syndrome (RS), clinical course together
with electroencephalography (EEG) and magnetic resonance imaging (MRI) findings
are considered important, but there are few reports on functional neuroimaging.
This study investigated cerebral blood flow (CBF)-single photon emission computed
tomography (SPECT), central benzodiazepine receptor (BZR)-SPECT, and fluorine-18
fluorodeoxy glucose-positron emission tomography (FDG-PET) in RS patients, and
correlated neuroimaging results with MRI and pathological findings. METHODS:
Twenty-three patients diagnosed with RS according to Bien's (2005) diagnostic
criteria (including 12 patients with a histological diagnosis) were studied. CBF
SPECT, BZR-SPECT and FDG-PET images were visually evaluated, and the findings
correlated with MRI and histological findings. RESULTS: Hypoperfusion areas were
observed in 16 of 22 patients by interictal CBF-SPECT. Hyperperfusion areas were
observed in 10 of 12 patients by ictal CBF-SPECT, which correlated with ictal
onset area by ictal EEG (IOAE). In the limited data of BZR-SPECT in nine
patients, lowered uptake was detected in all nine patients, including two with no
MRI abnormalities. Lowered glucose metabolism was observed in affected areas in
all five patients by FDG-PET. Histological examination revealed findings of
chronic encephalitis in all 12 patients examined, concomitant with focal cortical
dysplasia in five patients. CONCLUSION: In RS patients, functional neuroimaging
reveals clear abnormal findings, even before the appearance of MRI abnormalities.
BZR-SPECT and FDG-PET could detect the IOAE efficiently even in the absence of
MRI abnormalities, while interictal CBF-SPECT occasionally failed to detect IOAE
if MRI was normal. Based on BZR-SPECT, refractory epileptic seizures in RS may
suggest possible impairment of inhibitory neurons.
PMID- 29331847
TI - Longitudinal hippocampal and extra-hippocampal microstructural and
macrostructural changes following temporal lobe epilepsy surgery.
AB - OBJECTIVES: 1) Characterize the evolution of microstructural changes in the
contralateral, non-operated hippocampus-using longitudinal diffusion tensor
imaging (DTI)-following surgery for temporal lobe epilepsy (TLE). 2) Characterize
the downstream extra-hippocampal volumetric changes of the fornix and mammillary
bodies after TLE surgery. 3) Examine the relationship between these measures and
seizure/cognitive outcome. METHODS: Serial structural and DTI brain MRI scans
were collected in 25 TLE patients pre- and post-surgery (anterior temporal
lobectomy, ATL - 13; selective amygdalohippocampectomy, SelAH - 12) and in 12
healthy controls. Contralateral hippocampal fractional anisotropy (FA), mean
diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were
computed with manual hippocampal tracings as volumes of interest following co
registration to anatomical images. Fornix and mammillary body volumetry was
performed by manual segmentation. RESULTS: After surgery, the non-resected
hippocampus showed significant postoperative decline in FA (p = 0.0001), with
increase of MD (p = 0.01) and RD (p = 0.0001). In contrast to the timing of our
previously reported volume changes where atrophy is observed in the first week,
diffusion changes occurred late, taking 1-3 years to develop and are not
significant at one week after surgery. Diffusion changes are accompanied by
delayed limbic circuit volume loss in the mammillary bodies (35%; p < 0.0001) and
fornix (24%; p < 0.0001) compared to baseline. There was no correlation between
postoperative diffusion or structural changes and memory score nor did the degree
of postoperative change in hippocampal DTI parameters, mammillary body volume or
fornix volume vary significantly based on seizure outcome. SIGNIFICANCE:
Differences observed in the timing of postoperative volume (first week) and FA/MD
(one year) changes would suggest that early contralateral hippocampal atrophy is
not secondary to fluid shifts (dehydration) while the late DTI changes suggest
ongoing microstructural changes extending beyond the early postoperative period.
Postoperative hippocampal diffusion changes are accompanied by delayed mammillary
body and fornix volume loss which did not differ when stratified by seizure
outcome nor was correlated with degree of hippocampal diffusion change. Finally,
we did not identify any significant correlation between postoperative diffusion
parameter change and memory performance.
PMID- 29331848
TI - Repetitive transcranial magnetic stimulation for apathy in mild cognitive
impairment: A double-blind, randomized, sham-controlled, cross-over pilot study.
AB - Apathy is a common and disabling behavioral concomitant of many neurodegenerative
conditions. The presence of apathy with Mild Cognitive Impairment (MCI) is linked
with heightened rates of conversion to Alzheimer's disease. Improving apathy may
slow the neurodegenerative process. The objective was to establish the efficacy
of repetitive transcranial magnetic stimulation (rTMS) in improving apathy in
older adults with MCI. An 8-week, double-blind, randomized, sham-controlled cross
over study was conducted in nine subjects (66 +/- 9 years) with apathy and MCI.
Subjects were randomized to rTMS or sham treatment (5 days/week) for 2 weeks
following which they underwent a 4-week treatment-free period. Subjects then
crossed-over to receive the other treatment for 2 weeks. The primary (apathy (AES
C)) and secondary (cognition (3MS & MMSE), executive function (TMT-A & TMT-B),
and clinical global impression (CGI)) outcomes were assessed at baseline, 2, 6,
and 8 weeks. After adjusting for baseline, there was a significantly greater
improvement in the AES-C with rTMS compared to sham treatment at 2 weeks. There
was significantly greater improvement in 3MS, MMSE, TMT-A, and CGI-I with rTMS
compared to the sham treatment. This study establishes that rTMS is efficacious
in improving apathy in subjects with MCI.
PMID- 29331849
TI - Sociodemographic, lifestyle and health determinants of suicidal behaviour in
Malaysia.
AB - Suicide has become a serious matter in both developed and developing countries.
The objective of the present study is to examine the factors affecting suicidal
behaviour among adults in Malaysia. A nationally representative data which
consists of 10,141 respondents is used for analysis. A trivariate probit model is
utilised to identify the probability of having suicide ideation, suicide plan and
suicide attempt. Results of the regression analysis show that to ensure unbiased
estimates, a trivariate probit model should be used instead of three separate
probit models. The determining factors of suicidal behaviour are income, age,
gender, ethnicity, education, marital status, self-rated health and being
diagnosed with diabetes and hypercholesterolemia. The likelihood of adopting
suicidal behaviour is lower among higher income earners and older individuals.
Being male and married significantly reduce the propensity to engage in suicidal
behaviour. Of all the ethnic groups, Indian/others displays the highest
likelihood of adopting suicidal behaviour. There is a positive relationship
between poor health condition and suicide. Policies targeted at individuals who
are likely to adopt suicidal behaviour may be effective in lowering the
prevalence of suicide.
PMID- 29331850
TI - Attentional biases in patients suffering from unipolar depression: results of a
dot probe task investigation.
AB - Cognitive models of depression emphasize the relevance of cognitive biases for
development, onset and maintenance of major depressive disorder (MDD).
Attentional biases consisting of increased attention to negative, mood congruent
stimuli and reduced attention to positive, mood-incongruent stimuli are
postulated but have rarely been tested for early attentional processing.
Furthermore, the role of concurrent depressive mood as a moderating factor has
not been studied to date. Participants comprised 30 patients suffering from MDD
and 30 healthy control subjects. All participants performed a dot-probe task with
pictorial stimuli displaying affective facial expressions, presented either for
100ms or for 500ms. Attentional biases towards faces displaying joy in both MDD
patients and control subjects and towards faces displaying pain in MDD subjects
were found at presentation times of 100ms. In the MDD sample, the bias indices at
100ms were correlated with concurrent depressive mood. In patients with
pronounced depressive mood, significant biases towards happy and angry faces were
observed that exceed the biases obtained in control subjects and patients with
less depressive mood. The results provide first evidence that MDD patients with
pronounced depressive mood show an increased early attentional engagement towards
emotional salient stimuli, independent from valence.
PMID- 29331851
TI - Rhizospheric microorganisms as a solution for the recovery of soils contaminated
by petroleum: A review.
AB - Petroleum is currently the world's main energy source, and its demand is expected
to increase in coming years. Its intense exploitation can lead to an increase in
the number of environmental accidents, such as spills and leaks, and an increase
in the generation of environmental liabilities resulting from refining. Due to
its hydrophobic characteristics and slow process of biodegradation, petroleum can
remain in the environment for a long time and its toxicity can cause a negative
impact on both terrestrial and aquatic ecosystems, with the main negative effects
related to its carcinogenic potential for both animals and humans. The objective
of the present review is to discuss environmental contamination by oil,
conventional treatment techniques and bioremediation an alternative tool for
recovery petroleum-contaminated soils, focusing on the rhizodegradation process,
plant growth-promoting rhizobacteria (PGPR), a phytoremediation strategy in which
the microorganisms that colonize the roots of phytoremediatior plants are
responsible for the biodegradation of petroleum. These microorganisms can be
selected and tested individually or in the form of consortia to evaluate their
potential for oil degradation, or even to measure the use of biosurfactants
produced by them to constitute tools for the development of environmental
recovery strategies and biotechnological application.
PMID- 29331852
TI - No time to waste organic waste: Nanosizing converts remains of food processing
into refined materials.
AB - Modern food processing results in considerable amounts of side-products, such as
grape seeds, walnut shells, spent coffee grounds, and harvested tomato plants.
These materials are still rich in valuable and biologically active substances and
therefore of interest from the perspective of waste management and "up-cycling".
In contrast to traditional, often time consuming and low-value uses, such as
vermicomposting and anaerobic digestion, the complete conversion into
nanosuspensions unlocks considerable potentials of and new applications for such
already spent organic materials without the need of extraction and without
producing any additional waste. In this study, nanosuspensions were produced
using a sequence of milling and homogenization methods, including High Speed
Stirring (HSS) and High Pressure Homogenization (HPH) which reduced the size of
the particles to 200-400 nm. The resulting nanosuspensions demonstrated
nematicidal and antimicrobial activity and their antioxidant activities exceeded
the ones of the bulk materials. In the future, this simple nanosizing approach
may fulfil several important objectives, such as reducing and turning readily
available waste into new value and eventually closing a crucial cycle of
agricultural products returning to their fields - with a resounding ecological
impact in the fields of medicine, agriculture, cosmetics and fermentation.
Moreover, up-cycling via nanosizing adds an economical promise of increased value
to residue-free waste management.
PMID- 29331853
TI - Mobility of heavy metals in sandy soil after application of composts produced
from maize straw, sewage sludge and biochar.
AB - Studies on the availability of heavy metals in composted organic materials and in
soil amended with these materials are of practical significance. They are used in
the assessment of the purity of the soil environment and of the biological value
of plants intended for human and animal consumption. Composting of organic
materials has a significant effect on changes in mobile forms of heavy metals.
Therefore, the aim of this study was to determine the effect of the addition of
biochar and sewage sludge on (i) the contents of water soluble forms of Cu, Cd,
Pb, and Zn in composts; and (ii) the contents of mobile forms of these elements
in sandy soil after the addition of composts. Addition of sewage sludge and
biochar to maize straw did not increase the heavy metal forms extracted with
water in total content of heavy metals. The content of Cd and Cu extracted with
water in composts produced from maize straw and sewage sludge, and produced from
maize straw, sewage sludge and biochar was higher than the one determined in
compost produced from maize straw. The content of Pb and Zn extracted with water
in compost produced from maize straw, sewage sludge and biochar was lower than in
compost produced from maize straw. The addition of sewage sludge and biochar to
maize straw had an immobilizing effect on mobile forms of the studied elements
compared to compost produced from maize straw and sewage sludge. The addition of
composts to soil decreased the contents of mobile forms of Cu, Cd, and Pb
extracted with 1 M NH4NO3 compared to the contents in the control soil. However,
the content of Zn extracted with NH4NO3 increased in treatments with 0.5% dose of
compost produced from maize straw and sewage sludge and 0.5% dose of compost
produced from maize straw, sewage sludge and biochar. In none of the analyzed
cases, the application of the composts produced did not exceed the acceptable
content of studied elements in the soil.
PMID- 29331854
TI - Trade-offs between forest carbon stocks and harvests in a steady state - A multi
criteria analysis.
AB - This paper provides a perspective for comparing trade-offs between harvested wood
flows and forest carbon stocks with different forest management regimes. A
constant management regime applied to a forest area with an even age-class
distribution leads to a steady state, in which the annual harvest and carbon
stocks remain constant over time. As both are desirable - carbon stocks for
mitigating climate change and harvests for the economic use of wood and
displacing fossil fuels - an ideal strategy should be chosen from a set of
management regimes that are Pareto-optimal in the sense of multi-criteria
decision-making. When choosing between Pareto-optimal alternatives, the trade-off
between carbon stock and harvests is unavoidable. This trade-off can be described
e.g. in terms of carbon payback times or carbon returns. As numerical examples,
we present steady-state harvest levels and carbon stocks in a Finnish boreal
forest region for different rotation periods, thinning intensities and collection
patterns for harvest residues. In the set of simulated management practices,
harvest residue collection presents the most favorable trade-off with payback
times around 30-40 years; while Pareto-optimal changes in rotation or thinnings
exhibited payback times over 100 years, or alternatively carbon returns below 1%.
By extending the rotation period and using less-intensive thinnings compared to
current practices, the steady-state carbon stocks could be increased by half
while maintaining current harvest levels. Additional cases with longer rotation
periods should be also considered, but were here excluded due to the lack of
reliable data on older forest stands.
PMID- 29331855
TI - Retrievable Inferior vena cava filters in pregnancy: Risk versus benefit?
AB - OBJECTIVE: Venous thromboembolism remains one of the leading causes of maternal
mortality in the developed world. Retrievable inferior vena cava (IVC) filters
have a role in the prevention of lethal pulmonary emboli when anticoagulation is
contraindicated or has failed [1]. It is unclear whether or not the physiological
changes in pregnancy influence efficacy and complications of these devices. The
decision to place an IVC filter in pregnancy is complex and there is limited
information in terms of benefit and risk to the mother. The objective of this
study was to determine the efficacy and safety of these devices in pregnancy and
to compare these with rates reported in the general population. STUDY DESIGN: The
aim of this study was report three recent cases of retrievable IVC filter use in
pregnant women in our department and to perform a systematic review of the
literature to identify published cases of filters in pregnancy. The efficacy and
complication rates of these devices in pregnancy were estimated and compared to
rates reported in the general population in a recent review [2]. Fisher's exact
test was used for statistical analysis. RESULTS: In addition to our three cases,
16 publications were identified with retrievable IVC filter use in 40 pregnant
women resulting in a total of 43 cases. There was no pulmonary embolus in the
pregnant group (0/43) compared to 57/6291 (0.9%) in the general population.
Thrombosis of the filter (2.3% vs. 0.9%, p = 0.33) and perforation of the IVC
(7.0% vs 4.4%, p = 0.44) were more common in pregnancy compared to the general
population but the difference was not statistically significant. Failure to
retrieve the filter is more likely to occur in pregnancy (26% vs. 11%, p = 0.006)
but this did not correlate with the type of device (p = 0.61), duration of
insertion (p = 0.58) or mode of delivery (p = 0.37). CONCLUSION: Data for
retrievable IVC filters in pregnancy is limited and there may be a publication
bias towards complicated cases. This study shows that the filter appears to
protect against PE in pregnancy but the numbers are small. Complications such as
filter thrombosis and IVC penetration appear to be higher in pregnancy but this
difference is not statistically significant. It is not possible to retrieve the
device in one out of every four pregnant women. This has implications in terms of
long term risk of lower limb thrombosis and post thrombotic syndrome. The
decision to use an IVC filter in pregnancy needs careful consideration by a
multidisciplinary team. The benefit and risk assessment should be individualised
and clearly outlined to the patient.
PMID- 29331856
TI - Schizandrin A enhances chemosensitivity of colon carcinoma cells to 5
fluorouracil through up-regulation of miR-195.
AB - Nowadays 5-fluorouracil (5-FU)-based adjuvant chemotherapy is widely used for
treating colon carcinoma. However, 5-FU resistance in the treatment of colon
carcinoma has become more common and thereby new therapeutic strategies and new
adjuvant drugs still need to be explored. Two 5-FU-resistant colon cancer cell
lines, HCT116 and SW480, were used to investigate the effects of Schizandrin A
(SchA), 5-FU, or their combination on cell viability and apoptosis. Besides, the
role of miR-195 was studied to further clarify the specific function of SchA. CCK
8 assay and flow cytometry analysis were conducted to determine cell viability
and apoptosis, respectively. miR-195 expression was determined by quantitative
real-time PCR. Cell apoptosis-related proteins and factors of PI3K/AKT and NF
kappaB pathways were analyzed by Western blot. Cell viability assay showed that
SchA treatment at non-toxic dosages caused a marked enhancement of 5-FU-induced
cytotoxicity. Moreover, we explored that miR-195 was up-regulated by SchA; and
overexpression of miR-195 reduced cell viability and sensitized 5-FU-resistant
HCT116 and SW480 cells to 5-FU. The promoting effect of SchA on 5-FU
susceptibility can be partly abolished by miR-195 knockdown. Thus it was
speculated that SchA might enhance cell chemosensitivity to 5-FU by up-regulating
miR-195. Finally, we found that PI3K/AKT and NF-kappaB pathways were inhibited by
high expression of miR-195 reduced by SchA. Our results suggested that SchA
sensitized 5-FU-resistant colon carcinoma cells to 5-FU by up-regulating miR-195.
SchA combined with 5-FU could be a promising strategy for the adjuvant
chemotherapy of colon cancer.
PMID- 29331857
TI - Baicalin alleviates IL-1beta-induced inflammatory injury via down-regulating miR
126 in chondrocytes.
AB - Baicalin is a flavonoid extracted from Scutellaria baicalensis Georgi, with anti
inflammatory and anti-apoptotic activities. The objective of this study was to
explore the effect and mechanism of baicalin on chondrocyte inflammatory response
in OA. Different concentrations of IL-1beta (0, 0.1, 2, 5 and 10 ng/mL) were used
to simulate inflammatory injury in CHON-001 cells. The expression of miR-126 was
altered by transfection with miR-126 mimic. Thereafter, cells were treated with
baicalin, and cell viability, apoptosis, the expressions of apoptosis-related
protein and pro-inflammatory factors were respectively detected using CCK-8
assay, flow cytometry, qRT-PCR and western blot analysis. We found that IL-1beta
induced a significantly inflammatory injury in CHON-001 cells. Baicalin
alleviated IL-1beta-induced inflammatory injury, as it increased cell viability,
decreased cell apoptosis and repressed the production of IL-6, IL-8 and TNF
alpha. miR-126 was up-regulated by IL-1beta treatment while was down-regulated by
baicalin. More interestingly, the protective actions of baicalin on IL-1beta
injured CHON-001 cells were partially eliminated by miR-126 overexpression.
Further, NF-kappaB signaling pathway was activated by IL-1beta, and deactivated
by addition of baicalin. The deactivation of NF-kappaB signaling pathway induced
by baicalin upon IL-1beta exposure was recovered by miR-126 overexpression. In
conclusion, this study demonstrated that baicalin protected CHON-001 cells
against IL-1beta-induced inflammatory injury possibly via down-regulation of miR
126 and thereby deactivation of NF-kappaB signaling pathway.
PMID- 29331858
TI - Down-regulation of long non-coding RNA AFAP1-AS1 inhibits tumor growth, promotes
apoptosis and decreases metastasis in thyroid cancer.
AB - Long non-coding RNAs (lncRNAs), a new type of transcripts, play important roles
in various cellular biological processes, involving tumorigenesis. Previous
studies showed that lncRNA AFAP1-AS1 was aberrantly expressed in numerous
cancers. Nevertheless, we know quite a little about the expression pattern and
biological function of AFAP1-AS1 in thyroid cancer. In this study, we adopted the
quantitative real-time PCR (qRT-PCR) to detect the expression of AFAP1-AS1 in
thyroid cancer tissues. We discovered that expression of AFAP1-AS1 was increased
in thyroid cancer tissues. MTT assays elucidated that down-regulation of AFAP1
AS1 could suppress growth of thyroid cancer cells. And the results of flow
cytometry analysis indicated knockdown of AFAP1-AS1 induced apoptosis in thyroid
cancer. Transwell assay was applied to show decreased cell migration in thyroid
cancer as a result of down-regulation of AFAP1-AS1. Hence, our study provided
evidence for our hypothesis that AFAP1-AS1 could be a therapeutic target for
thyroid cancer.
PMID- 29331859
TI - Development of a method to determine axitinib, lapatinib and afatinib in plasma
by micellar liquid chromatography and validation by the European Medicines Agency
guidelines.
AB - A method based on micellar liquid chromatography to quantify the tyrosine kinase
inhibitors axitinib, lapatinib and afatinib in plasma is reported. The sample
pretreatment was a simple 1/5-dilution in a pure micellar solution, filtration
and direct injection, without requiring extraction or purification steps. The
three drugs were resolved from the matrix in 17min, using an aqueous solution of
0.07M sodium dodecyl sulfate - 6.0% 1-pentanol, buffered at pH7 with 0.01M
phosphate salt as mobile phase, running under isocratic mode at 1mL/min through a
C18 column. The detection was performed by absorbance at 260nm. An accurate
mathematical relationship was established between the retention factor of each
drug and the surfactant/organic solvent concentration in the mobile phase,
achieved with a limited number of experiments, in order to optimize these
factors. A binding behavior of the analytes face to the micelles was found out.
The method was successfully validated by the guidelines of the European Medicines
Agency in terms of: selectivity, linearity (r2>0.9995), calibration range (0.5 to
10mg/L), limit of detection (0.2mg/L), carry-over effect, accuracy (-8.1 to
+6.9%), precision (<13.8%), dilution integrity, matrix effect, stability and
robustness. The procedure was found reliable, practical, economic, accessible,
short-time, easy-to-handle, inexpensive, environmental-friendly, safe, useful for
the analysis of many samples per day. Finally, the method was applied to the
analysis of incurred, using quality control samples in the same analytical run,
with adequate results. Therefore, it can be implementable for routine analysis in
clinical laboratories.
PMID- 29331860
TI - C18 core-shell column with in-series absorbance and fluorescence detection for
simultaneous monitoring of changes in stilbenoid and proanthocyanidin
concentrations during grape cane storage.
AB - Grape canes, the residues from the annual pruning of vines, contain high levels
of inducible (E)-resveratrol and also oligomeric stilbenoids and
proanthocyanidins. These two families of phenolic compounds are bioactive, but to
quantify them in a single chromatographic run using only ultraviolet detection is
a difficult task. To overcome this limitation, a chromatographic method was
developed using a core shell column for separation, an ultraviolet-visible diode
array detector (DAD) and a fluorescence (FL) detector connected in series for
quantification, with an electrospray ionization interface (ESI) and a triple
quadrupole mass spectrometric detector (MS/MS) added for identification of the
analytes. The proanthocyanidins (+)-catechin, (-)-epicatechin, procyanidins B1,
B2, and C1, an unknown dimer and trimer, two prodelphinidin dimers, and
monogallate procyanidin dimers were detected in the tested grape cane samples.
The stilbenoids detected were (E)-resveratrol, (E)-piceatannol, (E)-piceid, (E)
epsilon-viniferin, vitisin B, a glycosylated monomer, three oxidized dimers, an
unknown dimer and a tetramer, pallidol, hopeaphenol, (E)-delta-viniferin, and (E)
omega-viniferin. However, this method required 60min for each analysis. A faster
and more efficient method for quantitative analysis was developed based on HPLC
DAD-FL, reducing the time required to 24min for the simultaneous quantification
of proanthocyanidins and stilbenoids in Cabernet Sauvignon, Pinot Noir, and
Tintorera grape canes stored at controlled temperatures and relativity humidities
for 134days after pruning. To the best of our knowledge, this is the first time a
prodelphinidin dimer has been quantified in grape canes. The incorporation of
fluorescence detection in series with DAD not only allowed the quantification of
proanthocyanidins, it also improved the detectability of some minor stilbenoids
present in the canes, such as (E)-piceid. The (E)-resveratrol and (E)-piceatannol
levels increased significantly during cane storage, while those of (E)-epsilon
viniferin and ampelopsin A did not show significant increases. The relative
humidity had a determining effect on the levels of (E)-resveratrol and (E)
piceatannol in the canes of all varieties studied; their concentrations were
higher at a relative humidity of 60% than at 70%. This is the first time that the
proanthocyanidin profiles of canes stored after pruning were monitored under
controlled conditions of temperature, time and relative humidity. The
concentration of (-)-epicatechin decreased during storage under both relative
humidities. Furthermore, the levels of proanthocyanidin B1 and the prodelphinidin
dimer also decreased to a certain extent.
PMID- 29331861
TI - Synthesis of colloidal silver nanoparticle clusters and their application in
ascorbic acid detection by SERS.
AB - Ascorbic acid (vitamin C) has an essential role in the human body mainly due to
its antioxidant function. In this work, metallic silver nanoparticle (AgNP)
colloids were used in SERS experiments to detect ascorbic acid in aqueous
solution. The AgNPs were synthesized by a green method using potato starch as
reducing and stabilizing agent, and water as the solvent. The optical properties
of the yellowish as-synthesized silver colloids were characterized by UV-vis
spectroscopy, in which besides a typical band at 410 nm related to the localized
surface plasmon resonance of the silver nanoparticles, a shoulder band around 500
nm, due to silver nanoparticle cluster formation, is presented when relatively
higher concentrations of starch are used in the synthesis. These starch-capped
silver nanoparticles show an intrinsic Raman peak at 1386 cm-1 assigned to
deformation modes of the starch structure. The increase of the intensity of the
SERS peak at 1386 cm-1 with an increase in the concentration of the ascorbic acid
is related to a decrease of the gap between dimers and trimers of the silver
nanoparticle clusters produced by the presence of ascorbic acid in the colloid.
The limit of detection of this technique for ascorbic acid is 0.02 mM with a
measurement concentration range of 0.02-10 mM, which is relevant for the
application of this method for detecting ascorbic acid in biological specimen.
PMID- 29331862
TI - Preliminary investigation of the use of Raman spectroscopy to predict meat and
eating quality traits of beef loins.
AB - A preliminary investigation was conducted to determine the potential for a
handheld Raman spectroscopic device to predict sensory traits determined by an
untrained consumer panel. Measurement of 45 beef loins (M. longissimus lumborum)
was conducted using a 671nm handheld Raman spectroscopic device. Samples were
then held frozen until testing by an untrained sensory panel. Sections were also
excised to determine shear force values and other indicators of meat quality.
Derived models suggest that the Raman spectroscopic device can predict juiciness
and tenderness, with correlations between predicted and observed values (rho) of
0.42 and 0.47, respectively. Spectra indicated that these predictions were
characterised by the fatty acid concentration, the hydrophobicity of proteins and
the orientation of collagen. However, future research is required to determine
the repeatability and robustness of these models on a larger independent data
set.
PMID- 29331863
TI - Airborne volatile aromatic hydrocarbons at an urban monitoring station in Korea
from 2013 to 2015.
AB - The concentrations of C6-C10 volatile aromatic hydrocarbons (AHCs) in air were
measured at an urban air quality monitoring station in Jong-Ro, Seoul, Korea,
between 2013 and 2015. Their temporal patterns (e.g., diurnal, intraweek, daily)
were assessed individually and collectively as groups of benzene, toluene,
ethylbenzene, styrene, and xylene (BTESX); total aliphatic hydrocarbon (TALHC: C2
C12); total aromatic hydrocarbon (TARHC: C6-C10); and total hydrocarbon (THC: C2
C12). The highest mean AHC concentrations over the 3-year study (in ppb (v/v))
were observed for toluene (6.0 +/- 4.3), followed by the xylenes (1.5 +/- 1.3),
ethylbenzene (0.85 +/- 0.93), benzene (0.73 +/- 0.77), and styrene (0.16 +/-
0.30) nL/L. The mean ppbC ((v/v), nL?atm?C/nL?atm) values for BTESX, TALHC,
TARHC, and THC were 65.8, 113, 77.7, and 191 ppbC, respectively. For most AHC
species (e.g., toluene, styrene, and BTESX), only weak seasonal trends were
observed in contrast to temporally varying species like nitric oxide (NO) (e.g.,
26.3 ppb (January-February) vs. 8.5 ppb (July-August) during weekdays in 2013).
Furthermore, toluene and NO concentrations were much higher (up to a factor 3) on
weekdays than on Sunday for most weeks. This might reflect reduced anthropogenic
activities on Sunday.
PMID- 29331864
TI - Taxonomic studies on Aegyria apoliva sp. nov. and Trithigmostoma cucullulus
(Muller, 1786) Jankowski, 1967 (Ciliophora, Cyrtophoria) with phylogenetic
analyses.
AB - The morphology, including the ciliary pattern, of two cyrtophorid ciliates,
namely Aegyria apoliva sp. nov. and Trithigmostoma cucullulus (Muller, 1786)
Jankowski, 1967, were investigated. They were isolated from coastal water off
Qingdao and from an estuarine habitat in south China, respectively. Aegyria
apoliva sp. nov. is characterized as following: body size 100-120 * 50-70 MUm in
vivo with dark pigment spot on anterior left part of cell; 48-69 somatic
kineties; one preoral and four or five circumoral kineties; 9-13 transpodial
segments; 26-40 nematodesmal rods; 6-10 contractile vacuoles. The Guangzhou
population of Trithigmostoma cucullulus corresponds well with previously
described populations, therefore only a brief morphological description is
presented. Phylogenetic analysis based on small-subunit rRNA gene sequences data
supports the establishment of the new species as well as the monophyly of both
genera.
PMID- 29331865
TI - Structure-based assessment of protein-protein interactions and accessibility of
protein IX in adenoviruses with implications for antigen display.
AB - The exterior minor protein IX of adenoviruses (AdVs) is a frequent target of
attachment of antigens and the modified AdVs are being used as potent vaccine
platforms. The organization of protein IX is disticntly different between human
adenoviruses (HAdVs) and non-HAdVs. The analysis of solvent accessibility, based
on the near atomic resolution structures, suggests that the C-terminal residues
of IX are more accessible in non-HAdVs (e.g., bovine adenovirus) than in HAdVs.
Although the C-terminal fusions of IX are displayed on the capsid surface, they
could disrupt the formation of tetrameric coiled-coils (4-HLXB) in HAdVs due to
steric hinderance, thereby potentially affecting the capsid stability.
Importantly, the parallel-antiparallel arrangement of helices seen in the 4-HLXB
is not condusive for IX C-terminal fusions in HAdVs. In contrast, the parallel
trimeric C-terminal coiled-coils in non-HAdVs are unlikely to be affected by the
attachment of antigens and more efficiently displayed on the AdV surface.
PMID- 29331868
TI - Zinc supplementation alleviates the progression of diabetic nephropathy by
inhibiting the overexpression of oxidative-stress-mediated molecular markers in
streptozotocin-induced experimental rats.
AB - Zinc deficiency during diabetes projects a role for zinc nutrition in the
management of diabetic nephropathy. The current study explored whether zinc
supplementation protects against diabetic nephropathy through modulation of
kidney oxidative stress and stress-induced expression related to the inflammatory
process in streptozotocin-induced diabetic rats. Groups of hyperglycemic rats
were exposed to dietary interventions for 6 weeks with zinc supplementation (5
times and 10 times the normal level). Supplemental-zinc-fed diabetic groups
showed a significant reversal of increased kidney weight and creatinine
clearance. There was a significant reduction in hyperlipidemic condition along
with improved PUFA:SFA ratio in the renal tissue. Expression of the lipid
oxidative marker and expression of inflammatory markers, cytokines, fibrosis
factors and apoptotic regulatory proteins observed in diabetic kidney were
beneficially modulated by zinc supplementation, the ameliorative effect being
concomitant with elevated antiapoptosis. There was a significant reduction in
advanced glycation, expression of the receptor of the glycated products and
oxidative stress markers. Zinc supplementation countered the higher activity and
expression of polyol pathway enzymes in the kidney. Overexpression of the glucose
transporters, as an adaptation to the increased need for glucose transport in
diabetic condition, was minimized by zinc treatment. The pathological
abnormalities in the renal architecture of diabetic animals were corrected by
zinc intervention. Thus, dietary zinc supplementation has a significant
beneficial effect in the control of diabetic nephropathy. This was exerted
through a protective influence on oxidative-stress-induced cytokines,
inflammatory proliferation and consequent renal injury.
PMID- 29331866
TI - Development of a novel equine influenza virus live-attenuated vaccine.
AB - H3N8 equine influenza virus (EIV) is an important and significant respiratory
pathogen of horses. EIV is enzootic in Europe and North America, mainly due to
the suboptimal efficacy of current vaccines. We describe, for the first time, the
generation of a temperature sensitive (ts) H3N8 EIV live-attenuated influenza
vaccine (LAIV) using reverse-genetics approaches. Our EIV LAIV was attenuated
(att) in vivo and able to induce, upon a single intranasal administration,
protection against H3N8 EIV wild-type (WT) challenge in both a mouse model and
the natural host, the horse. Notably, since our EIV LAIV was generated using
reverse genetics, the vaccine can be easily updated against drifting or emerging
strains of EIV using the safety backbone of our EIV LAIV as master donor virus
(MDV). These results demonstrate the feasibility of implementing a novel EIV LAIV
approach for the prevention and control of currently circulating H3N8 EIVs in
horse populations.
PMID- 29331869
TI - Dietary naringenin supplementation attenuates experimental autoimmune
encephalomyelitis by modulating autoimmune inflammatory responses in mice.
AB - Autoimmune disease is highly prevalent in humans. Since conventional therapies
have limited efficacy and often come with significant side effects, nutrition may
provide an alternative and complementary approach to improving autoimmune
disorders. Naringenin, a flavonoid found in citrus fruits, has been shown to have
anti-inflammatory and antioxidant properties. Using the experimental autoimmune
encephalomyelitis (EAE), a rodent model of human multiple sclerosis, we
determined the effect of dietary naringenin (0.5%) on autoimmune disease. We
found that naringenin reduced the incidence, delayed the onset, and attenuated
the symptoms of EAE, which were accompanied by reduced immune cell infiltration
and demyelination in the spinal cord. Additionally, the pro-inflammatory CD4+ T
cell subsets Th1, Th9, and Th17 cells together with their respective
transcription factors T-bet, PU.1, and RORgammat were reduced in both the central
nervous system (CNS) and lymph nodes of EAE mice fed naringenin while no
difference was found in Th2 and regulatory T cell (Treg) populations in either
CNS or lymph nodes between the two groups. We further showed that pathologic T
cell proliferation induced by ex vivo re-stimulation with MOG35-55 and
proinflammatory cytokines IL-6 and TNF-alpha were lower in naringenin-fed mice
than in the control mice. Additionally, we found that naringenin treatment
inhibited mRNA expression of CXCL10 (Th1 recruiting chemokine), vascular cell
adhesion molecule-1 (VCAM-1), and VLA-4 (VCAM-1 ligand) in the CNS of EAE mice.
Altogether, these results indicate that naringenin may have a potential to
ameliorate autoimmune disease by favorably modulating autoimmune response.
PMID- 29331867
TI - Classification and evolution of human papillomavirus genome variants: Alpha-5
(HPV26, 51, 69, 82), Alpha-6 (HPV30, 53, 56, 66), Alpha-11 (HPV34, 73), Alpha-13
(HPV54) and Alpha-3 (HPV61).
AB - HPV variants from the same type can be classified into lineages and sublineages
based on the complete genome differences and the phylogenetic topologies. We
examined nucleotide variations of twelve HPV types within the species Alpha-5
(HPV26, 51, 69, 82), Alpha-6 (HPV30, 53, 56, 66), Alpha-11 (HPV34, 73), Alpha-13
(HPV54) and Alpha-3 (HPV61) by analyzing 1432 partial sequences and 181 complete
genomes from multiple geographic populations. The inter-lineage and inter
sublineage mean differences of HPV variants ranged between 0.9-7.3% and 0.3-0.9%,
respectively. The heterogeneity and phylogenies of HPV isolates indicate an
independent evolutionary history for each type. The noncoding regions were the
most variable regions whereas the capsid proteins were relatively conserved.
Certain variant lineages and/or sublineages were geographically-associated. These
data provide the basis to further classify HPV variants and should foster future
studies on the evolution of HPV genomes and the associations of HPV variants with
cancer risk.
PMID- 29331870
TI - Postural instability differences between idiopathic normal pressure hydrocephalus
and Parkinson's disease.
AB - OBJECTIVES: We investigated the differences in postural control disability
between idiopathic normal pressure hydrocephalus (iNPH) and Parkinson's disease
(PD). PATIENTS AND METHODS: Twenty-seven iNPH patients, 20 PD patients, and 20
healthy controls (HCs) were examined using the Timed Up and Go test (TUG) and a
force platform for recording the center of pressure (COP) trajectory during
quiescent standing and voluntary multidirectional leaning (forward, backward,
right, and left for 10 s each). RESULTS: In the leaning task, postural control in
PD patients was impaired during forward and backward leaning, whereas postural
control in iNPH patients was impaired in all directions. In particular, postural
control during right and left leaning was significantly worse in iNPH patients
than in PD patients. No significant difference was observed between iNPH and PD
patients in TUG and postural sway during quiescent standing. CONCLUSION: Our
results showed that the characteristics of impaired voluntary COP control in iNPH
and PD patients might reflect pathophysiological differences in postural
instability for each disease. In particular, postural instability during right
and left leaning in iNPH patients may be responsible for wider steps and a higher
risk of falling.
PMID- 29331871
TI - Rupture during coiling of intracranial aneurysms: Predictors and clinical
outcome.
AB - INTRODUCTION: The intraprocedural aneurysm rupture (IPR) is one of the most
feared adverse effect associated with the coil embolization therapy. The aim of
the study was to identify predisposing factors for IPR, as well as to define
patient groups with worse clinical outcome following IPR. PATIENTS AND METHODS:
From February 2008 to March 2015, 273 consecutive patients were treated at our
institution via endovascular coil embolization. Patient medical records were
reviewed with emphasis on procedure description, potential risk factors and
clinical outcomes related to IPR. The IPR occurred in 14 (5.13%) cases.
Multivariate logistic regression models were used to determine independent
predictors of IPR. Clinical outcome was analyzed using the Glasgow Outcome Scale
(GOS). RESULTS: Multivariate analysis showed that aneurysm location at posterior
communicating artery is an independent risk factor for IPR (p = 0.035; OR 3.5;
95%CI 1.09-11.26). The frequencies of favorable disability (GOS 4-5), severe
disability (GOS 2-3), and mortality (GOS 1) between patients with IPR and without
IPR were significantly different in the general study population (p < 0.001, p <
0.001 and p = 0.023, respectively) and in patients with previously unruptured
aneurysms (p < 0.001, p = 0.006 and p = 0.003, respectively) but not in patients
with previously ruptured aneurysms (p = 0.187, p = 0.089 and p = 1.0,
respectively). CONCLUSION: Posterior communicating artery aneurysm location is an
independent predictor for IPR. IPR is associated with a significant clinical
deterioration in a subgroup of patients with previously unruptured aneurysms, but
not in patients with ruptured aneurysms.
PMID- 29331873
TI - Epilepsy and ovarian failure: Two cases of adolescent-onset ovarioleukodystrophy.
AB - Vanishing white matter disease (VWM) was described by Van der Knaap in 1996. This
association with premature ovarian failure is known as ovarioleukodystrophy. This
is a rare entity caused by a mutation in one of the subunits of eukaryotic
initiation factor 2B (EIF2B). The onset in adulthood or late in adolescence is
very infrequent. A 41-years-old woman and her 37-years-old sister developed
epilepsy in association with premature ovarian failure at the age of 13 and 18
respectively. The oldest-one started 17 years later progressive subcortical
cognitive decline with predominant behavioural disorders and a progressive
spastic paraparesis in association with symmetric cystic changes in the with
matter of both hemispheres. In both patients we found the c.1117C>T (p.Arg373Cys)
mutation in homozygosis in the EIF2B4 gen.
PMID- 29331872
TI - Effect of physical activity on cognitive flexibility, depression and RBD in
healthy elderly.
AB - OBJECTIVE: The prevalence of Alzheimer's disease and Parkinson's disease
increases with the raising number of elderly, which will be a challenging
situation for the healthcare systems and society in the future. There is evidence
that there are modifiable risk-factors e.g. physical activity for these diseases.
Here, we study the interaction between sports inactivity with prodromal markers
for neurodegeneration. PATIENTS AND METHODS: We investigated 667 neurologically
healthy individuals cross-sectional and a subgroup longitudinal over six years.
Participants were stratified by their weekly sports activity. Prodromal markers
(depression and REM sleep behaviour disorder (RBD)) as well as single and dual
tasking parameters and cognitive parameters were compared between the groups.
RESULTS: At baseline, sports activity was associated with lower BDI scores, lower
occurrence of depressive syndrome and RBD, compared to sports inactivity.
Further, active participants were faster in cognitive tasks associated with
working memory and attention (Trail Making test part-A; TMT-B, DeltaTMT-B-A) and
better in gait and cognition parameters (single tasks and dual tasks) but not
with overall cognition as measured with the MMSE. The association between
physical inactivity and depression as well as TMT was present after six years.
CONCLUSION: We found that sports activity has a positive effect on cognitive
flexibility, depressive symptoms and sleep which are all signs for a possible
ongoing neurodegenerative process. Therefore, our results strengthen the
potential role of sports activity as a positive disease modifier.
PMID- 29331874
TI - Thyroid hormone resuscitation after brain death in potential organ donors: A
primer for neurocritical care providers and narrative review of the literature.
AB - Solid organ transplantation has become a mainstay in the contemporary management
of end-stage organ failures fueled by advances in immunosuppression, intensive
care and surgical technology. Every year, a vast number of transplantable organs
is lost on account of hemodynamic instability in potential brain-dead organ
donors. Because of a growing organ shortage, measures that increase total donor
supply pools are desperately needed. Thyroid hormone has been identified as an
adjunctive therapy in donor management due to its potential for increasing organ
supply and is currently endorsed by transplant organizations such as United
Network for Organ Sharing (UNOS). Much of the evidence in support of thyroid
hormone comes from level III studies showing greater donor survival and
procurement rates. However, all prospective randomized studies to date have
failed to corroborate any such benefit. Here, we describe the role of thyroid
hormone in transplantation medicine and summarize data on its putative
contributions to circulatory stability, organ yield and long-term graft function.
At present, level I studies do not exist and many level II studies, which do not
endorse its use, are of poor quality. Further research, particularly large-scale
multi-center trials are therefore warranted to shed light on this matter.
PMID- 29331875
TI - The association between vitamin D receptor polymorphisms and multiple sclerosis
in a Turkish population.
AB - BACKGROUND: Multiple sclerosis (MS) is a chronic, demyelinating disease of the
central nervous system (CNS). Genetic and environmental factors are important in
disease development. Many studies have investigated the relationship between MS
and VDR polymorphisms. VDR gene polymorphism has not been previously studied in
Turkish MS patients. We aimed to investigate the relationship between MS and VDR
genotypes Taq I, Apa I and Fok I polymorphisms in a Turkish population. METHODS:
167 MS patients and 146 healthy control subjects were included in the present
study. MS and the VDR TaqI (rs731236), ApaI (rs7975232), and FokI (rs2228570)
polymorphisms were investigated. RESULTS: The study enrolled 167 patients (121
females, 46 males) with MS and 146 healthy individuals (88 females, 58 males).
The frequency of only the Fok I polymorphism differed significantly between the
two groups (p = 0.002). The TaqI (rs731236) and ApaI (rs7975232) genotype
distributions were not significantly different between MS patients and healthy
controls (p = 0.626 and p = 0.990, respectively). Also there were no significant
gender difference between patients and controls for Taq I and Apa I. CONCLUSION:
In conclusion, we found a significant association between MS and the FokI
polymorphism in our region of Turkey. However, the results may be different in
other populations. More epidemiological and genetic studies are needed to explain
the association between genetic factors and MS.
PMID- 29331876
TI - APP/Go protein Gbetagamma-complex signaling mediates Abeta degeneration and
cognitive impairment in Alzheimer's disease models.
AB - Deposition of amyloid-beta (Abeta), the proteolytic product of the amyloid
precursor protein (APP), might cause neurodegeneration and cognitive decline in
Alzheimer's disease (AD). However, the direct involvement of APP in the mechanism
of Abeta-induced degeneration in AD remains on debate. Here, we analyzed the
interaction of APP with heterotrimeric Go protein in primary hippocampal cultures
and found that Abeta deposition dramatically enhanced APP-Go protein interaction
in dystrophic neurites. APP overexpression rendered neurons vulnerable to Abeta
toxicity by a mechanism that required Go-Gbetagamma complex signaling and p38
mitogen-activated protein kinase activation. Gallein, a selective pharmacological
inhibitor of Gbetagamma complex, inhibited Abeta-induced dendritic and axonal
dystrophy, abnormal tau phosphorylation, synaptic loss, and neuronal cell death
in hippocampal neurons expressing endogenous protein levels. In the 3xTg-AD mice,
intrahippocampal application of gallein reversed memory impairment associated
with early Abeta pathology. Our data provide further evidence for the involvement
of APP/Go protein in Abeta-induced degeneration and reveal that Gbetagamma
complex is a signaling target potentially relevant for developing therapies for
halting Abeta degeneration in AD.
PMID- 29331878
TI - How shared reality is created in interpersonal communication.
AB - Communication is a key arena and means for shared-reality creation. Most studies
explicitly devoted to shared reality have focused on the opening part of a
conversation, that is, a speaker's initial message to an audience. The aspect of
communication examined by this research is the evaluative adaptation (tuning) of
the messages to the audience's attitude or judgment. The speaker's shared-reality
creation is typically assessed by the extent to which the speaker's evaluative
representation of the topic matches the audience-tuned view expressed in the
message. We first review research on such audience-tuning effects, with a focus
on shared-reality goals and conditions facilitating the generalization of shared
reality. We then review studies using other paradigms that illustrate factors of
shared-reality creation in communication, including mere message production,
grounding, validation responses, and communication about commonly known
information (including stereotypes) in intragroup communication. The different
lines of research reveal the potency, but also boundary conditions, of
communication effects on shared reality.
PMID- 29331877
TI - Cerebral changes and disrupted gray matter cortical networks in asymptomatic
older adults at risk for Alzheimer's disease.
AB - The diagnostic value of cerebrospinal fluid (CSF) biomarkers is well established
in Alzheimer's disease, but our current knowledge about how abnormal CSF levels
affect cerebral integrity, at local and network levels, is incomplete in
asymptomatic older adults. Here, we have collected CSF samples and performed
structural magnetic resonance imaging scans in cognitively normal elderly as part
of a cross-sectional multicenter study (SIGNAL project). To identify group
differences in cortical thickness, white matter volume, and properties of
structural networks, participants were split into controls (N = 20), positive
amyloid-beta (Abeta1-42+) (N = 19), and positive phosphorylated tau (N = 18). The
Abeta1-42+ group exhibited thickening of middle temporal regions, while positive
phosphorylated tau individuals showed thinning in the superior parietal and
orbitofrontal cortices. Subjects with abnormal CSF biomarkers further showed
regional white matter atrophy and more segregated cortical networks, the Abeta1
42+ group showing heightened isolation of cingulate and temporal cortices.
Collectively, these findings highlight the relevance of combining structural
brain imaging and connectomics for in vivo tracking of Alzheimer's disease
lesions in asymptomatic stages.
PMID- 29331879
TI - Structural and quantum mechanical computations to elucidate the altered binding
mechanism of metal and drug with pyrazinamidase from Mycobacterium tuberculosis
due to mutagenicity.
AB - Pyrazinamide is known to be the most effective treatment against tuberculosis
disease and is known to have bacteriostatic action. By targeting the bacterial
spores, this drug reduces the chances for the progression of the infection in
organisms. In recent years, increased instances of the drug resistance of
bacterial strains are reported. Pyrazinamidase, activator for pyrazinamide, leads
to resistance against the drug due to mutagenicity across the world. The present
study aimed at the quantum mechanistic analysis of mutations in pyrazinamidase to
gain insights into the mechanism of this enzyme. Quantum mechanical calculations
were performed to analyse the effect of mutations at the metal coordination site
using ORCA software program. Moreover, conformational changes in PZase binding
cavity has also been analysed due to mutations of binding pocket residues using
CASTp server. In order to elucidate the behaviour of the mutant pyrazinamidase,
docking of PZA in the binding pocket of PZase was performed using AutoDock Vina.
Analysis of results revealed that iron showed weak binding with the metal
coordination site of the mutant proteins due to alteration in electron transfer
mechanism. The binding cavity of the mutant PZase has undergone major
conformational changes as the volume of pocket increased due to bulky R-chains of
mutated amino acids. These conformational changes lead to weak binding of the
drug at binding cavity of PZase and reduce the drug activation mechanism leading
to increased drug resistance in the bacterial strains.
PMID- 29331881
TI - Ameliorative role of genistein against age-dependent chronic arsenic toxicity in
murine brains via the regulation of oxidative stress and inflammatory signaling
cascades.
AB - Brain is highly prone to oxidative damage due to its huge lipid content and
extensive energy requirements. Exogenous insult in brain via oxidative injury can
lead to severe pathophysiological conditions. Age-dependent deterioration of
normal brain functions is also noteworthy. Genistein, a polyphenolic
isoflavonoid, obtained from the soy plant, is well known to protect against
several diseased conditions. Here, in this study chronic brain toxicity model was
developed using oral administration of arsenic for 90 days in adult and aged
murines. We observed that intraperitoneal administration of genistein improved
the arsenic induced behavioral abnormalities in the rats. It was also evident
from the histopathological studies that the extent of tissue damage due to
arsenic exposure was more in aged rats compared to the adults. Evaluation of
different stress markers, intracellular ROS level and mitochondrial membrane
potential revealed the involvement of oxidative stress and mitochondrial
dysfunction in inducing brain damage in arsenic exposed murines. It was observed
that genistein can significantly ameliorate the stressed condition in both the
animal groups but the protective effect of genistein was more significant in the
adult animals. The underlying signalling mechanism behind the cytotoxicity of
arsenic was investigated and revealed that genistein exhibited neuroprotection
significantly by modulating the JNK3 mediated apoptosis, ERK1/2 mediated
autophagy and TNFalpha associated inflammatory pathways. Overall study infers
that genistein has significant ameliorative effect of against age-dependent
cytotoxicity of arsenic in murine brains.
PMID- 29331882
TI - Association analysis of SLC6A4 and HTR2A genes with obsessive-compulsive
disorder: Influence of the STin2 polymorphism.
AB - BACKGROUND: Obsessive-Compulsive Disorder (OCD) is a complex and chronic disorder
characterized by recurrent thoughts and/or repetitive behaviors. Given the potent
anti-obsessional effects of the so-called serotonin reuptake inhibitors, genes
related to serotonergic system may be well implicated in the etiopathogenesis of
OCD. The gene encoding the serotonin transporter (SLC6A4), which shows a variable
number of tandem repeat (VNTR) polymorphism in intron 2 (STin2), have been
previously associated with OCD. Additionally, the serotonin 2A receptor gene
(HTR2A) has two polymorphisms (A-1438G - rs6311, and T102C - rs6313), which have
also been overrepresented among OCD patients. Therefore, the aim of this study is
to evaluate the association of these three polymorphisms with OCD, through the
examination of potential sources of heterogeneity in previous studies including
age of onset, sex and symptom dimensions. METHODS: Polymorphisms were genotyped
by Polymerase Chain Reaction (PCR) in a sample of 203 OCD patients and 205
healthy controls from Brazil. RESULTS: Although we did not observe any
statistically significant association between the HTR2A gene polymorphisms and
OCD or its clinical features, SLC6A4 STin2 polymorphism was significantly more
common among OCD patients as compared to health controls. Further, a significant
association between the STin2.12 allele and OCD, as well as a dominant effect of
the STin2.12 allele in OCD was seen. Of note, late-onset (>18years) OCD was
significantly more often seen in association with homozygosis for STin2.12
allele. No significant associations were observed with different OCD symptom
dimensions. CONCLUSION: Our results indicate an important influence of the STin2
polymorphism in OCD, but more studies are warranted to confirm these results.
PMID- 29331880
TI - Preventive effects of indole-3-carbinol against alcohol-induced liver injury in
mice via antioxidant, anti-inflammatory, and anti-apoptotic mechanisms: Role of
gut-liver-adipose tissue axis.
AB - Indole-3-carbinol (I3C), found in Brassica family vegetables, exhibits
antioxidant, anti-inflammatory, and anti-cancerous properties. Here, we aimed to
evaluate the preventive effects of I3C against ethanol (EtOH)-induced liver
injury and study the protective mechanism(s) by using the well-established
chronic-plus-binge alcohol exposure model. The preventive effects of I3C were
evaluated by conducting various histological, biochemical, and real-time PCR
analyses in mouse liver, adipose tissue, and colon, since functional alterations
of adipose tissue and intestine can also participate in promoting EtOH-induced
liver damage. Daily treatment with I3C alleviated EtOH-induced liver injury and
hepatocyte apoptosis, but not steatosis, by attenuating elevated oxidative
stress, as evidenced by the decreased levels of hepatic lipid peroxidation,
hydrogen peroxide, CYP2E1, NADPH-oxidase, and protein acetylation with
maintenance of mitochondrial complex I, II, and III protein levels and
activities. I3C also restored the hepatic antioxidant capacity by preventing EtOH
induced suppression of glutathione contents and mitochondrial aldehyde
dehydrogenase-2 activity. I3C preventive effects were also achieved by
attenuating the increased levels of hepatic proinflammatory cytokines, including
IL1beta, and neutrophil infiltration. I3C also attenuated EtOH-induced gut
leakiness with decreased serum endotoxin levels through preventing EtOH-induced
oxidative stress, apoptosis of enterocytes, and alteration of tight junction
protein claudin-1. Furthermore, I3C alleviated adipose tissue inflammation and
decreased free fatty acid release. Collectively, I3C prevented EtOH-induced liver
injury via attenuating the damaging effect of ethanol on the gut-liver-adipose
tissue axis. Therefore, I3C may also have a high potential for translational
research in treating or preventing other types of hepatic injury associated with
oxidative stress and inflammation.
PMID- 29331883
TI - Curative distal pancreatectomy in patients with acinar cell carcinoma of pancreas
diagnosed by endoscopic aspiration via esophago-jejunostomy: A successful case
report.
AB - INTRODUCTION: This is a case report on the advances in preoperative endoscopic
guided fine-needle-aspiration (FNA) diagnosis for pancreatic carcinoma to achieve
a curative operation even in patients who have a history of total gastrectomy.
CASE PRESENTATION: A 65-year-old man, who underwent total gastrectomy for gastric
cancer 13 years ago, had discomfort in the left lateral abdomen. A 3-cm
hypovascular mass accompanying a large distal pseudocyst in the pancreatic tail
was observed on computed tomography. Endoscopic ultrasonography via elevation of
the jejunal loop on esophago-jejunostomy also revealed similar lesions, and FNA
for the proximal-side hypoechoic mass was successful. The cytological diagnosis
with immunohistochemistry was acinar cell carcinoma of the pancreas. Distal
pancreatectomy with splenectomy was successfully performed. Histology of the
resected specimen also showed the acinar cell carcinoma, similar with
preoperative cytology, which involved the splenic vein and had extra-pancreatic
extension but no lymph node metastasis. The tumor stage was IIA by the 2009 UICC
classification. He had no tumor relapse on imaging follow-up until 12 months
after the operation. DISCUSSION: There have been marked technical advancements in
endoscopic ultrasonography-guided diagnosis, including FNA, even in patients with
prior digestive tract surgery. However, the risk of complication is still a
concern. Accurate histological diagnosis is useful in the field of pancreatic
surgery, especially in cases of rare or small malignant lesions. CONCLUSION:
Curative pancreatectomy was possible in a case of acinar cell carcinoma, a rare
pancreatic malignancy, which was diagnosed by preoperative endoscopic FNA
diagnosis via esophago-jejunostomy after previous total gastrectomy.
PMID- 29331884
TI - True left-sided gallbladder: A case report and comparison with the literature for
the different techniques of laparoscopic cholecystectomy for such anomalies.
AB - INTRODUCTION: True left-sided gallbladder (LSG) is a rare finding that may
present with symptoms similar to those of a normally positioned gallbladder.
Moreover, it may be missed by preoperative imaging studies such as ultrasound,
computed tomography (CT), magnetic resonance imaging (MRI), or endoscopic
ultrasound. True left-sided gallbladder is a surgical challenge and surgical
technique may need to be modified for the completion of laparoscopic
cholecystectomy. PRESENTATION OF CASE: In this case report, we present a case of
true left-sided gallbladder that produced right-sided abdominal symptoms.
Ultrasound of the abdomen failed to show the left-sided position of the
gallbladder. MRI showed the gallbladder located to the left of the ligamentum
teres underneath segment III of the liver. Intraoperatively, the gallbladder was
grasped and retracted to the right under the falciform ligament and it was
removed using classical right-sided ports with no modification to the technique.
No complications were encountered intraoperatively or postoperatively.
DISCUSSION: True LSG is a rare anomaly that may present with right-sided symptoms
like normally positioned gallbladder. It may be missed in preoperative imaging
studies and can be discovered only intraoperatively. Modification of laparoscopic
ports, change in patient's position and/or surgeon's position, or conversion to
open cholecystectomy may be needed for safe removal of the gallbladder.
CONCLUSION: Classical technique of laparoscopic cholecystectomy is feasible for
left-sided gallbladder. However, if the anatomy is not clear, modifications of
the surgical technique may be necessary for the safe dissection of the
gallbladder.
PMID- 29331885
TI - Autonomously hyperfunctioning cystic nodule harbouring thyroid carcinoma - Case
report and literature review.
AB - INTRODUCTION: Hyperthyroidism is rarely associated with malignancy, but it cannot
rule out thyroid cancer. Although there is published data describing this
coexistence, thyroid carcinomas inside autonomously functioning nodules are
uncommon. PRESENTATION OF CASE: A 49-year-old woman presented with a cervical
mass, unexplained weight loss and anxiousness, sweating and insomnia. On physical
examination, she had a palpable left thyroid nodule. Thyroid function tests
showed suppressed TSH (<0,1 uUI/mL), thyroxine 1,44 ng/dL (normal range 0,70
1,48) and triiodothyronine 4,33 pg/mL (normal range 1,71-3,71). Ultrasound
imaging revealed a left lobe, 4 cm partial cystic nodule. 99mTC thyroid
scintigraphy showed a hyperfunctioning nodule with suppression of the remainder
parenchyma. Fine-needle aspiration cytology was nondiagnostic (cystic fluid). The
patient was started on thiamazole 5 mg daily with subsequent normalization of
thyroid function, but she developed cervical foreign body sensation and a left
hemithyroidectomy was performed. Histology showed a 4 cm cystic nodule with a
follicular variant papillary carcinoma and the patient underwent completion
thyroidectomy, followed by radio-iodine ablation. DISCUSSION: Published
literature showed an increased prevalence of autonomously functioning nodules,
harbouring thyroid carcinomas in adults. Papillary carcinoma is the most
frequently described but the follicular variant is rare. CONCLUSION: Although
rare, thyroid cancer is not definitively excluded in hyperthyroid patients and it
should always be considered as differential diagnosis.
PMID- 29331886
TI - Anti-cancer Effects of HNHA and Lenvatinib by the Suppression of EMT-Mediated
Drug Resistance in Cancer Stem Cells.
AB - Anaplastic thyroid cancer (ATC) constitutes less than 2% of total thyroid cancers
but accounts for 20-40% of thyroid cancer-related deaths. Cancer stem cell drug
resistance represents a primary factor hindering treatment. This study aimed to
develop targeted agents against thyroid malignancy, focusing on individual and
synergistic effects of HNHA (histone deacetylase), lenvatinib (FGFR), and
sorafenib (tyrosine kinase) inhibitors. Patients with biochemically and
histologically proven papillary thyroid cancer (PTC) and ATC were included. Cell
samples were obtained from patients at the Thyroid Cancer Center, Gangnam
Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. PTC and
ATC cells were treated with lenvatinib or sorafenib, alone or in combination with
HNHA. Tumor-bearing mice (10/group) were administered 10 mg/kg lenvatinib (p.o.)
or 40 mg/kg sorafenib (p.o.), alone or in combination with 25 mg/kg HNHA (i.p.)
once every three days. Gene expression in patient-derived PTC and ATC cells was
compared using a microarray approach. Cellular apoptosis and proliferation were
examined by immunohistochemistry and MTT assays. Tumor volume and cell properties
were examined in the mouse xenograft model. HNHA-lenvatinib combined treatment
induced markers of cell cycle arrest and apoptosis and suppressed anti-apoptosis
markers, epithelial-mesenchymal transition (EMT), and the FGFR signaling pathway.
Combined treatment induced significant tumor shrinkage in the xenograft model.
HNHA-lenvatinib combination treatment thus blocked the FGFR signaling pathway,
which is important for EMT. Treatment with HNHA-lenvatinib combination was more
effective than either agent alone or sorafenib-HNHA combination. These findings
have implications for ATC treatment by preventing drug resistance in cancer stem
cells.
PMID- 29331888
TI - A Longitudinal Analysis of IDO and PDL1 Expression during Immune- or Targeted
Therapy in Advanced Melanoma.
AB - A deepened understanding of the cellular and molecular processes in the tumor
microenvironment is necessary for the development of precision immunotherapy
(IT). We simultaneously investigated CD3, PDL1, and IDO by immunohistochemistry
in paired biopsies from various organs of 43 metastatic melanoma patients treated
with IT and targeted therapy (TT). Intraindividual biopsies taken after a period
of weeks to months demonstrate discordant results in 30% of the cases. Overlap of
IDO and PDL1 increased after therapy. IT only marginally impacted PDL1 expression
over time in contrast to TT. Standardized repeated assessments of multiple immune
markers in repeated biopsies will generate detailed insights in melanoma's immune
evolution and adaption during therapies and might be used to support treatment
decisions.
PMID- 29331889
TI - L-ascorbic acid metabolism in an ascorbate-rich kiwifruit (Actinidia. Eriantha
Benth.) cv. 'White' during postharvest.
AB - Kiwifruit (Actinidia eriantha Benth.) 'White', a novel cultivar with higher L
ascorbic acid (AsA) level, is registered in China. Changes in AsA, related
metabolites, enzymatic activity, and gene expression associated with AsA
biosynthesis and recycling process were investigated in this paper. The results
indicated that AsA biosynthesis through L-galactose pathway supplemented by D
galacturonic acid pathway and AsA recycling collectively contributed to
accumulating and remaining higher AsA level in kiwifruit cv. 'White' during
postharvest. Moreover, L-galactose dehydrogenase (GalDH) activity and relative
expressions of the genes encoding GDP-D-mannose pyrophosphorylase (GMP), L
galactose-1-P phosphatase (GPP), GDP-L-galactose phosphorylase (GGP), GalDH and D
galacturonate reductase (GalUR) were important for regulation of AsA
biosynthesis, and the activity and expression of dehydroascorbate reductase
(DHAR) were primarily responsible for regulation of AsA recycling in kiwifruit
'White' during postharvest.
PMID- 29331887
TI - IDH1R132H Promotes Malignant Transformation of Benign Prostatic Epithelium by
Dysregulating MicroRNAs: Involvement of IGF1R-AKT/STAT3 Signaling Pathway.
AB - Risk stratification using molecular features could potentially help distinguish
indolent from aggressive prostate cancer (PCa). Mutations in isocitrate
dehydrogenase (IDH) acquire an abnormal enzymatic activity, resulting in the
production of 2-hydroxyglutarate and alterations in cellular metabolism, histone
modification, and DNA methylation. Mutant IDH1 has been identified in various
human malignancies, and IDH1R132H constituted the vast majority of mutational
events of IDH1. Most recent studies suggested that IDH1 mutations define a
methylator subtype in PCa. However, the function of IDH1R132H in PCa development
and progression is largely unknown. In this study, we showed that the prevalence
of IDH1R132H in Chinese PCa patients is 0.6% (2/336). Of note, IDH1R132H-mutant
PCa patients lacked other canonical genomic lesions (e.g., ERG rearrangement,
PTEN deletion) that are common in most other PCa patients. The in vitro
experiment suggested that IDH1R132H can promote proliferation of benign prostate
epithelial cell RWPE-1 when under the situation of low cytokine. It could also
promote migration capacity of RWPE-1 cells. Mechanistically, IDH1R132H was an
important regulator of insulin-like growth factor 1receptor (IGF1R) by
downregulating a set of microRNAs (miR-141-3p, miR-7-5p, miR-223-3p). These
microRNAs were repressed by the alteration of epigenetic modification to decrease
the enrichment of active marker H3K4me3 or to increase repressive marker H3K27me3
at their promoters. Collectively, we proposed a novel model for an IDH1R132H
microRNAs-IGF1R regulatory axis, which might provide insight into the function of
IDH1R132H in PCa development.
PMID- 29331890
TI - Deep sequence analysis reveals the ovine rumen as a reservoir of antibiotic
resistance genes.
AB - Antibiotic resistance is an increasingly important environmental pollutant with
direct consequences for human health. Identification of environmental sources of
antibiotic resistance genes (ARGs) makes it possible to follow their evolution
and prevent their entry into the clinical setting. ARGs have been found in
environmental sources exogenous to the original source and previous studies have
shown that these genes are capable of being transferred from livestock to humans.
Due to the nature of farming and the slaughter of ruminants for food, humans
interact with these animals in close proximity, and for this reason it is
important to consider the risks to human health. In this study, we characterised
the ARG populations in the ovine rumen, termed the resistome. This was done using
the Comprehensive Antibiotic Resistance Database (CARD) to identify the presence
of genes conferring resistance to antibiotics within the rumen. Genes were
successfully mapped to those that confer resistance to a total of 30 different
antibiotics. Daptomycin was identified as the most common antibiotic for which
resistance is present, suggesting that ruminants may be a source of daptomycin
ARGs. Colistin resistance, conferred by the gene pmrE, was also found to be
present within all samples, with an average abundance of 800 counts. Due to the
high abundance of some ARGs (against daptomycin) and the presence of rare ARGs
(against colistin), we suggest further study and monitoring of the rumen
resistome as a possible source of clinically relevant ARGs.
PMID- 29331892
TI - Dynamic probabilistic material flow analysis of nano-SiO2, nano iron oxides, nano
CeO2, nano-Al2O3, and quantum dots in seven European regions.
AB - Static environmental exposure assessment models based on material flow analysis
(MFA) have previously been used to estimate flows of engineered nanomaterials
(ENMs) to the environment. However, such models do not account for changes in the
system behavior over time. Dynamic MFA used in this study includes the time
dependent development of the modelling system by considering accumulation of ENMs
in stocks and the environment, and the dynamic release of ENMs from nano
products. In addition, this study also included regional variations in
population, waste management systems, and environmental compartments, which
subsequently influence the environmental release and concentrations of ENMs. We
have estimated the flows and release concentrations of nano-SiO2, nano-iron
oxides, nano-CeO2, nano-Al2O3, and quantum dots in the EU and six geographical
sub-regions in Europe (Central Europe, Northern Europe, Southern Europe, Eastern
Europe, South-eastern Europe, and Switzerland). The model predicts that a large
amount of ENMs are accumulated in stocks (not considering further
transformation). For example, in the EU 2040 Mt of nano-SiO2 are stored in the in
use stock, 80,400 tonnes have been accumulated in sediments and 65,600 tonnes in
natural and urban soil from 1990 to 2014. The magnitude of flows in waste
management processes in different regions varies because of differences in waste
handling. For example, concentrations in landfilled waste are lowest in South
eastern Europe due to dilution by the high amount of landfilled waste in the
region. The flows predicted in this work can serve as improved input data for
mechanistic environmental fate models and risk assessment studies compared to
previous estimates using static models.
PMID- 29331891
TI - Global association between ambient air pollution and blood pressure: A systematic
review and meta-analysis.
AB - Although numerous studies have investigated the association of ambient air
pollution with hypertension and blood pressure (BP), the results were
inconsistent. We performed a comprehensive systematic review and meta-analysis of
these studies. Seven international and Chinese databases were searched for
studies examining the associations of particulate (diameter<2.5 MUm (PM2.5), 2.5
10 MUm (PM2.5-10) or >10 MUm (PM10)) and gaseous (sulfur dioxide (SO2), nitrogen
dioxide (NO2), nitrogen oxides (NOx), ozone (O3), carbon monoxide (CO)) air
pollutants with hypertension or BP. Odds ratios (OR), regression coefficients
(beta) and their 95% confidence intervals were calculated to evaluate the
strength of the associations. Subgroup analysis, sensitivity analysis, and meta
regression analysis were also conducted. The overall meta-analysis showed
significant associations of long-term exposures to PM2.5 with hypertension (OR =
1.05), and of PM10, PM2.5, and NO2 with DBP (beta values: 0.47-0.86 mmHg). In
addition, short-term exposures to four (PM10, PM2.5, SO2, NO2), two (PM2.5 and
SO2), and four air pollutants (PM10, PM2.5, SO2, and NO2), were significantly
associated with hypertension (ORs: 1.05-1.10), SBP (beta values: 0.53-0.75 mmHg)
and DBP (beta values: 0.15-0.64 mmHg), respectively. Stratified analyses showed a
generally stronger relationship among studies of men, Asians, North Americans,
and areas with higher air pollutant levels. In conclusion, our study indicates a
positive association between ambient air pollution and increased BP and
hypertension. Geographical and socio-demographic factors may modify the pro
hypertensive effects of air pollutants.
PMID- 29331893
TI - Ambient volatile organic compounds (VOCs) in communities of the Athabasca oil
sands region: Sources and screening health risk assessment.
AB - An investigation of ambient levels and sources of volatile organic compounds
(VOCs) and associated public health risks was carried out at two northern Alberta
oil sands communities (Fort McKay and Fort McMurray located < 25 km and >30 km
from oil sands development, respectively) for the period January 2010-March 2015.
Levels of total detected VOCs were comparatively similar at both communities
(Fort McKay: geometric mean = 22.8 MUg/m3, interquartile range, IQR = 13.8-41
MUg/m3); (Fort McMurray: geometric mean = 23.3 MUg/m3, IQR = 12.0-41 MUg/m3). In
general, methanol (24%-50%), alkanes (26%-32%) and acetaldehyde (23%-30%) were
the predominant VOCs followed by acetone (20%-24%) and aromatics (~9%). Mean and
maximum ambient concentrations of selected hazardous VOCs were compared to health
risk screening criteria used by United States regulatory agencies. The Positive
matrix factorization (PMF) model was used to identify and apportion VOC sources
at Fort McKay and Fort McMurray. Five sources were identified at Fort McKay,
where four sources (oil sands fugitives, liquid/unburned fuel,
ethylbenzene/xylene-rich and petroleum processing) were oil sands related
emissions and contributed to 70% of total VOCs. At Fort McMurray six sources were
identified, where local sources other than oil sands development were also
observed. Contribution of aged air mass/regional transport including biomass
burning emissions was ~30% of total VOCs at both communities. Source-specific
carcinogenic and non-carcinogenic risk values were also calculated and were below
acceptable and safe levels of risk, except for aged air mass/regional transport
(at both communities), and ethylbenzene/xylene-rich (only at Fort McMurray).
PMID- 29331894
TI - Pharmaceutical concentration variability at sewage treatment plant outlets
dominated by hydrology and other factors.
AB - A study was conducted in which the effluent at four small to medium sized sewage
treatment plants (STP) in North Rhine-Westphalia, Germany was monitored for three
pharmaceutical compounds (carbamazepine, diclofenac, metoprolol) over a period of
four years. Grab sampling and auto sampling campaigns were accomplished with
respect to various weather conditions in the catchment area. Flow volumes and
hydraulic retention times (HRT) from various sampling dates which provide
information on processes causing emission changes were additionally taken into
account. Monitoring results showed that concentration scattering in the effluent
is related to HRT in the sewage treatment plants. Dilution effects following rain
events in the catchment area were analysed for the three investigated substances.
Short-term emission changes explained by dilution only could be well determined
by the mathematical relation between discharge and concentration, and for
carbamazepine to be solely determined by the dilution effects at all HRTs. For
metoprolol, a clear decrease in concentrations was observed at HRTs above 80 h,
and a significant contribution of biodegradation was supported by independent
biodegradation tests. For three out of the four STPs, a decrease in
concentrations of diclofenac was observed at hydraulic retention times above 80
h, indicating removal, whereas the relationship between concentration and HRT of
the other STP could be explained by dilution only. The study shows that emissions
can vary with weather conditions, hampering the assessment of emissions and
estimation of concentrations in surface waters from generic removal rates only.
Furthermore, it illustrates the importance of HRT of rather stable substances in
wastewater treatment.
PMID- 29331895
TI - Reduction in soil N2O emissions by pH manipulation and enhanced nosZ gene
transcription under different water regimes.
AB - Several studies have been carried out to examine nitrous oxide (N2O) emissions
from agricultural soils in the past. However, the emissions of N2O particularly
during amelioration of acidic soils have been rarely studied. We carried out the
present study using a rice-rapeseed rotation soil (pH 5.44) that was amended with
dolomite (0, 1 and 2 g kg-1 soil) under 60% water filled pore space (WFPS) and
flooding. N2O emissions and several soil properties (pH, NH4+N, NO3--N, and nosZ
gene transcripts) were measured throughout the study. The increase in soil pH
with dolomite application triggered soil N transformation and transcripts of nosZ
gene controlling N2O emissions under both water regimes (60% WFPS and flooding).
The 60% WFPS produced higher soil N2O emissions than that of flooding, and
dolomite largely reduced N2O emissions at higher pH under both water regimes
through enhanced transcription of nosZ gene. The results suggest that
ameliorating soil acidity with dolomite can substantially mitigate N2O emissions
through promoting nosZ gene transcription.
PMID- 29331896
TI - Environmentally available hexavalent chromium in soils and sediments impacted by
dispersed fly ash in Sarigkiol basin (Northern Greece).
AB - Hexavalent chromium is one of the most toxic and carcinogenic species known and
can be released into the environment from several sources. In Sarigkiol basin (N
Greece) the presence of Cr(VI) in soil, sediments and groundwater may originate
from both natural (ophiolitic rocks and their weathering products) and
anthropogenic (dispersed fly ash produced from lignite power plants) sources. In
this study, the distribution of contents and origin of environmentally available
Cr(VI) in soils, sediments, regoliths and fly ash of Sarigkiol basin is
presented. Detailed geochemical and mineralogical studies were performed on soil
samples (up to 1 m) and regoliths, while leaching tests were also applied to
fresh and old fly ash samples. Leachable chromium from soil and sediment samples
generally increased with depth and the highest concentrations were observed near
to the power plant of Agios Dimitrios. The speciation of chromium in leachates
revealed that Cr(VI) concentrations accounted for more than 96% of total Cr.
Leaching tests of regoliths established that the natural contribution of Cr(VI)
is up to 14 MUg kg-1. Therefore, the measurement of higher concentrations (up to
80 MUg kg-1) of environmentally available Cr(VI) in soils and sediments can be
attributed to the impact/presence of dispersed fly ash in the soils and sediments
of the same area. This was also supported by the low correlation recorded between
environmentally available chromium and Cr-bearing minerals (mainly serpentine and
talc). The influenced zone is located in the eastern part of the basin near the
local power plant and surrounds an open conveyor belt that transfers fly ash to
an open temporary storage pit. This zone overlies an unconfined porous aquifer
thus explaining the elevated concentrations of Cr(VI) in groundwater (up to 120
MUg L-1) previously reported in this area.
PMID- 29331897
TI - A framework for delineating the regional boundaries of PM2.5 pollution: A case
study of China.
AB - Fine particulate matter (PM2.5) pollution has been a major issue in many
countries. Considerable studies have demonstrated that PM2.5 pollution is a
regional issue, but little research has been done to investigate the regional
extent of PM2.5 pollution or to define areas in which PM2.5 pollutants interact.
To allow for a better understanding of the regional nature and spatial patterns
of PM2.5 pollution, This study proposes a novel framework for delineating
regional boundaries of PM2.5 pollution. The framework consists of four steps,
including cross-correlation analysis, time-series clustering, generation of
Voronoi polygons, and polygon smoothing using polynomial approximation with
exponential kernel method. Using the framework, the regional PM2.5 boundaries for
China are produced and the boundaries define areas where the monthly PM2.5 time
series of any two cities show, on average, more than 50% similarity with each
other. These areas demonstrate straightforwardly that PM2.5 pollution is not
limited to a single city or a single province. We also found that the PM2.5 areas
in China tend to be larger in cold months, but more fragmented in warm months,
suggesting that, in cold months, the interactions between PM2.5 concentrations in
adjacent cities are stronger than in warmer months. The proposed framework
provides a tool to delineate PM2.5 boundaries and identify areas where PM2.5
pollutants interact. It can help define air pollution management zones and assess
impacts related to PM2.5 pollution. It can also be used in analyses of other air
pollutants.
PMID- 29331898
TI - Coadsorption and subsequent redox conversion behaviors of As(III) and Cr(VI) on
Al-containing ferrihydrite.
AB - Naturally occurring ferrihydrite often contains various impurities, and Al is one
of the most prominent impurities. However, little is known about how these
impurities impact the physical and chemical properties of ferrihydrite with
respect to metal(loid) adsorption. In this study, a series of Al-containing
ferrihydrites were synthesized and exposed to a mixed solution containing As(III)
and Cr(VI). The results showed that the two contaminants can be quickly adsorbed
onto the surface of Al-containing ferrihydrite under acidic and neutral
conditions. With the increase of Al molar percentage in ferrihydrites from 0 to
30, the adsorption capacity of As(III) decreased, whereas it increased for
Cr(VI). On the other hand, with the increase of pH value from 3.0 to 11.0, the
decreasing rate of As(III) was accelerated first, then slowed down, whereas the
Cr(VI) decreasing rate slowed down dramatically. X-ray diffraction (XRD),
Brunauer-Emmett-Teller (BET) analysis method, transmission electron microscopy
(TEM) analysis, energy dispersive spectroscopy (EDS) mapping, Attenuated Total
Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR), and X-ray
photoelectron spectroscopy (XPS) were employed to characterize Al-containing
ferrihydrite. Interestingly, it was found that the redox transformation occurred
between As(III) and Cr(VI) after the two contaminants were coadsorbed onto the
surface of Al-containing ferrihydrite. The oxidation of As(III) to As(V) and
reduction of Cr(VI) to Cr(III) would greatly lower the environmental hazard of
the As(III) and Cr(VI).
PMID- 29331899
TI - The speed of memory errors shows the influence of misleading information: Testing
the diffusion model and discrete-state models.
AB - In this report, we evaluate single-item and forced-choice recognition memory for
the same items and use the resulting accuracy and reaction time data to test the
predictions of discrete-state and continuous models. For the single-item trials,
participants saw a word and indicated whether or not it was studied on a previous
list. The forced-choice trials had one studied and one non-studied word that both
appeared in the earlier single-item trials and both received the same response.
Thus, forced-choice trials always had one word with a previous correct response
and one with a previous error. Participants were asked to select the studied word
regardless of whether they previously called both words "studied" or "not
studied." The diffusion model predicts that forced-choice accuracy should be
lower when the word with a previous error had a fast versus a slow single-item
RT, because fast errors are associated with more compelling misleading memory
retrieval. The two-high-threshold (2HT) model does not share this prediction
because all errors are guesses, so error RT is not related to memory strength. A
low-threshold version of the discrete state approach predicts an effect similar
to the diffusion model, because errors are a mixture of responses based on
misleading retrieval and guesses, and the guesses should tend to be slower.
Results showed that faster single-trial errors were associated with lower forced
choice accuracy, as predicted by the diffusion and low-threshold models.
PMID- 29331900
TI - A catalytic and dual recycling amplification ATP sensor based on target-driven
allosteric structure switching of aptamer beacons.
AB - Abnormal concentrations of ATP are associated with many diseases and cancers, and
quantitative detection of ATP is thus of great importance for disease diagnosis
and prognosis. In the present work, we report a new dual recycling amplification
sensor integrated with catalytic hairpin assembly (CHA) to achieve high
sensitivity for fluorescent detection of ATP. The association of the target ATP
with the aptamer beacons causes the allosteric structure switching of the aptamer
beacons to expose the toehold regions, which hybridize with and unfold the
fluorescently quenched hairpin signal probes (HP1) to recycle the target ATP and
to trigger CHA between HP1 and the secondary hairpin probes (HP2) to form HP1/HP2
duplexes. Due to the recycling amplification, the presence of ATP leads to the
formation of many HP1/HP2 duplexes, generating dramatically amplified fluorescent
signals for sensitive detection of ATP. Under optimal experimental conditions,
our sensor linearly responds to ATP in the range from 25 to 600nM with a
calculated detection limit of 8.2nM. Furthermore, the sensor shows a high
selectivity and can also be used to detect ATP in human serums to realize its
application for real samples. With the distinct advantage of significant signal
amplification without the involvement of any nanomaterial and enzyme, the
developed sensor thus holds great potential for simple and sensitive detection of
different small molecules and proteins.
PMID- 29331901
TI - An ultrasensitive detection of miRNA-155 in breast cancer via direct
hybridization assay using two-dimensional molybdenum disulfide field-effect
transistor biosensor.
AB - MicroRNAs (miRNAs), critical biomarkers of acute and chronic diseases, play key
regulatory roles in many biological processes. As a result, robust assay
platforms to enable an accurate and efficient detection of low-level miRNAs in
complex biological samples are of great significance. In this work, a label-free
and direct hybridization assay using molybdenum disulfide (MoS2) field-effect
transistor (FET) biosensor has been developed for ultrasensitive detection of
miRNA-155 as a breast cancer biomarker in human serum and cell-line samples.
MoS2, the novel 2D layered material with excellent physical and chemical
properties, was prepared through sequential solvent exchange method and was used
as an active channel material. MoS2 was comprehensively characterized by
spectroscopic and microscopic methods and it was applied for fabrication of FET
device by drop-casting MoS2 flacks suspension onto the FET surface. MoS2 FET
device showed a relatively low subthreshold swing of 48.10mV/decade and a high
mobility of 1.98 * 103cm2V-1s-1. Subsequently, probe miRNA-155 strands were
immobilized on the surface of the MoS2 FET device. Under optimized conditions
detection limit of 0.03fM and concentration range 0.1fM to 10nM were achieved.
The developed biosensor not only was capable to identification of fully matched
versus one-base mismatch miRNA-155 sequence, but also it could detect target
miRNA-155 in spiked real human serum and extracts from human breast cancer cell
line samples. This approach paves a way for label-free, early detection of miRNA
as a biomarker in cancer diagnostics with very high sensitivity and good
specificity, thus offering a significant potential for clinical application.
PMID- 29331902
TI - The use of interprofessional learning and simulation in undergraduate nursing
programs to address interprofessional communication and collaboration: An
integrative review of the literature.
AB - OBJECTIVE: To identify how simulation and interprofessional learning are used
together in undergraduate nursing programs and undertaken in schools of nursing
to address interprofessional communication and collaboration. DESIGN: An
integrative literature review. DATA SOURCES: The databases CINAHL, ProQuest,
PubMed, Scopus, PsycInfo and Science Direct were searched to identify articles
from 2006 to 2016 that reported on the use of IPL and simulation together in
undergraduate nursing education. REVIEW METHOD: Whittemore and Knafl's five step
process was used to guide the integrative review of quantitative and qualitative
literature. Only peer reviewed articles written in English that addressed
undergraduate nursing studies, were included in the review. Articles that did not
aim to improve communication and collaboration were excluded. All articles
selected were examined to determine their contribution to interprofessional
learning and simulation in undergraduate nursing knowledge. RESULTS: The
faculties of nursing used interprofessional learning and simulation in
undergraduate nursing programs that in some cases were connected to a specific
course. A total of nine articles, eight research papers and one narrative report,
that focused on collaboration and communication were selected for this review.
Studies predominantly used nursing and medical student participants. None of the
included studies identified prior student experience with interprofessional
learning and simulation. Four key themes were identified: communication,
collaboration/teamwork, learning in practice and understanding of roles, and
communication. CONCLUSION: This review highlights the identified research
relating to the combined teaching strategy of interprofessional learning and
simulation that addressed communication and collaboration in undergraduate
nursing programs. Further research into the implementation of interprofessional
learning and simulation may benefit the emergent challenges. Information drawn
from this review can be used in informing education and educational development
in the future.
PMID- 29331903
TI - Rapid structure prediction by HPLC-ESI-MSn of twenty-five polyoxypregnane
tetraglycosides from Dregea sinensis with NMR confirmation of eight structures.
AB - Dregea sinensis Hemsl is an important herbal medicine in the Dai nationality of
China. Its prominent clinical application has generated interest in the
polyoxypregnane glycosides of the plant. This paper describes an extension of
previous research on the polyoxypregnane di- and triglycosides of D. sinensis,
aiming at identifying related tetraglycosides. On the basis of HPLC-ESI-MSn
analysis in positive mode, twenty-five previously undescribed polyoxypregnane
tetraglycosides were characterized (regarding molecular masses and fragmentation
in MSn) from an ethyl acetate fraction that was not previously investigated.
Guided by MSn fragmentation and known structures of related di- and triglycosides
from D. sinensis, tentative structures were predicted from the MS data. In order
to test the predictions, eight of the glycosides were isolated and their
structures were elucidated by 1D and 2D NMR methods, confirming the tentative
predictions. Finally, the cytotoxicity of the isolates was evaluated on several
human cell lines with little effect in general, even though slight inhibitory
effects of four polyoxypregnane glycosides were detected at 10 MUM against the
human leukemia cell line HL-60.
PMID- 29331904
TI - Anthocyanins in perilla plants and dried leaves.
AB - High-quality perilla leaves are purple on upper and lower surfaces and have a
good aroma. The Japanese Pharmacopoeia specifies the content of essential oils in
perilla leaves but not that of anthocyanins. Several reports have described the
chemical species of anthocyanins in red perilla, but a complete analysis of
anthocyanins in perilla has not been reported. In this study, the anthocyanins in
the leaves of cultivated and wild species of perilla and those in commercially
available perilla herbs were studied. Red perilla and most P. citriodora strains
accumulate cyanidin derivatives that differ in the acyl group on the glucose
moiety at the 3-O- and 5-O-positions of the anthocyanins. Several strains of P.
citriodora contain cyanidin derivatives that are different from those in red
perilla and most P. citriodora species. Green perilla and wild species other than
P. citriodora do not contain foliar anthocyanins. The anthocyanins in
commercially available perilla herbs and natural dyes made from red perilla were
in agreement with those in fresh red perilla leaves and most P. citriodora
samples. The amounts and types of anthocyanins were not associated with place of
cultivation, although some changes occurred due to degradation during storage.
These results provide clues regarding the biosynthesis of anthocyanins in perilla
and the evolution of red perilla. The characteristics and stability of
anthocyanins are discussed.
PMID- 29331905
TI - Macrophage phenotype switch by sequential action of immunomodulatory cytokines
from hydrogel layers on titania nanotubes.
AB - Inflammatory response occurring between tissues and implants after implantation
has attracted increasing attention because it can cause local tissue necrosis and
even implant failure. Macrophages play a key role in all stages of inflammation.
Pro-inflammatory (M1) and anti-inflammatory (M2) macrophages comprise two main
phenotypes and the switch from M1 to M2 at specific time points is important for
wound healing and tissue regeneration. Therefore, we hypothesized that
biomaterial systems capable of facilitating macrophage phenotype switching should
attenuate inflammation and enhance healing. To this end, a system of double
hydrogel layers on titania nanotubes (TNT) was prepared as reservoir to modulate
the release of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma). In this
system, IL-4, an anti-inflammatory cytokine, was loaded in TNT and IFN-gamma, a
pro-inflammatory cytokine, was located between two hydrogel layers of
chitosan/beta-glycerophosphate disodium and carboxymethyl chitosan/genipin. IFN
gamma released rapidly in 3 days, whereas IL-4 exhibited a sustained release
profile. In culture with mesenchymal stem cells and macrophages, this system
displayed good cytocompatibility and significantly promoted cell proliferation.
Macrophage phenotype switch was determined by ELISA, FACS and PCR. The results
manifested that IFN-gamma released from the system stimulated switching of
macrophages to M1 in 3 days, whereas sustained release of IL-4 polarized
macrophages to M2 after 4 days. This system can modulate macrophage phenotype
switching from M1 to M2 by sequential action of the two cytokines, and might be
used to research immune response between tissues and implants. The present study
also provided a novel strategy for designing functional biomaterials.
PMID- 29331906
TI - Strontium Hydroxyapatite scaffolds engineered with stem cells aid
osteointegration and osteogenesis in osteoporotic sheep model.
AB - Osteoporotic fracture healing is an orthopaedic challenge due to excessive bone
resorption and impaired osteogenesis. Majority of current treatment strategies
focus on regulating bone resorption and the potential application of Mesenchymal
Stem Cells (MSCs) in promoting osteogenesis has not been explored much.
Furthermore, the present study has put forth a novel approach, wherein the
synergistic action of Strontium (Sr) and MSCs in a single implant may facilitate
osteoporotic bone healing. Strontium Hydroxyapatite (SrHA) synthesized by wet
precipitation was fabricated into tissue engineered Strontium incorporated
Hydroxyapatite (cSrHA) using sheep adipose tissue derived MSCs (ADMSCs).
Porosity, radiopacity and cytocompatibility of SrHA scaffolds were found
appropriate for orthopaedic applications. cSrHA scaffolds exhibited an in vitro
Alkaline Phosphatase activity of 20 MUmol pnp/30 min comparable to that of
Hydroxyapatite (HA) - control scaffold, proving its osteogenic efficacy.
Implantation studies in sheep osteoporotic model depicted enhanced osteogenic
ability with mature lamellar bone formation in cSrHA implanted group, compared to
bare HA, SrHA and tissue engineered HA implanted groups. Histomorphometry data
substantiated improved osteogenesis on par with material resorption, as cSrHA
implanted group exhibited highest regeneration ratio of 0.38 +/- 0.05. Density
histograms from micro CT further signified the enhanced osteointegrative ability
of cSrHA implants. Results of the study depicted the therapeutic potential of
cSrHA in osteoporotic bone healing and proposes the use of allogenic ADMSCs for
fabricating "Off the Shelf Tissue Engineered Products".
PMID- 29331907
TI - Applying ultraviolet/persulfate (UV/PS) pre-oxidation for controlling
ultrafiltration membrane fouling by natural organic matter (NOM) in surface
water.
AB - Membrane fouling is a recognized obstacle for the application of ultrafiltration
(UF) for drinking water treatment. In this study, ultraviolet/persulfate (UV/PS)
oxidation was employed as a pretreatment to control membrane fouling caused by
natural organic matter (NOM) in surface water. The effects of UV/PS pretreatment
on amounts and characteristics of NOM were investigated in terms of dissolved
organic carbon, fluorescent spectrum, molecular weight distribution and
hydrophobicity. UF membrane fouling during filtration of raw and pre-oxidized
water was compared with transmembrane pressure development, and the fouled
membranes were further characterized using scanning electron microscopy (SEM) and
Fourier transform infrared spectroscopy (FTIR). The results indicate that NOM was
considerably degraded and partially mineralized (~58%) by UV/PS pretreatment at a
PS dose not exceeding 0.6 mM and a UV irradiation time within 120 min, which was
attributed to the generation of sulfate and hydroxyl radicals. The fluorescent
compounds in NOM were almost completely degraded (>98%) by the UV/PS pretreatment
at a PS dose of 0.4 mM, except for tyrosine-like proteins (~80%). Moreover, UV/PS
pretreatment decreased the ratio of macromolecular compounds and increased the
hydrophilic fractions, resulting in reduced NOM adhesion to the membrane. Hence,
irreversible fouling by NOM was significantly retarded (~75%) by the UV/PS
pretreatment due to reduction in NOM, and more importantly by preferential
degradation of fluorescent, macromolecular and hydrophobic compounds. Fouling
control performance was considerably improved at increased PS doses and extended
UV irradiation time.
PMID- 29331908
TI - Electricity production and phosphorous recovery as struvite from synthetic
wastewater using magnesium-air fuel cell electrocoagulation.
AB - This research was based on the investigation of a major principle, regarding the
effects of NaCl and KH2PO4 concentrations on struvite recovery, with electricity
production using magnesium-air fuel cell electrocoagulation, in accordance with
the concentration of phosphorous and chloride. The weight ratio of N:P in the
synthetic wastewater was in the range of 1.2-21. The concentration of NH4Cl was
fixed at 0.277 M (approximately 3888 ppm as NH3-N and 5000 ppm as NH4), while PO4
P was in the range of 0.006-0.1 M. In addition, the concentrations of NaCl as
electrolyte were 0, 0.01, and 0.1 M. Phosphate removal increased linearly with
the Mg:P ratio, up to approximately 1.1 mol mol-1, irrespective of the initial
concentrations of phosphate and NaCl. The one-to-one reaction as mole ratio
between phosphate and the dissolved Mg ions resulted in phosphate removal, with
the production of a one-to-one magnesium/phosphate mineral, such as struvite. The
average removal rate of phosphorous in experiments without a dose of NaCl was
4.19 mg P cm-2 h-1, which was lower than the relative values of 5.35 and 4.77 mg
P cm-2 h-1, in experiments with 0.01 and 0.1 M NaCl. The dissolution rate of Mg
with electro-oxidation determined the rate of phosphorous removal with struvite
recovery. The average removal rates of phosphorous with dose concentrations of
0.006, 0.01 and 0.02 M KH2PO4 were 4.02, 5.54, 6.9 mg P cm-2 h-1, respectively,
which increased with the increase in KH2PO4 dose. However, in experiments with a
dose of 0.05 and 0.1 M KH2PO4, the average removal rates of phosphorous decreased
to 4.84 and 2.51, respectively. The maximum power densities in the electrolyte
mixture of 0.05 M KH2PO4/0.277 M NH4Cl, 0.01 M NaCl/0.05 M KH2PO4/0.277 M NH4Cl,
and 0.1 NaCl/0.05 KH2PO4/0.277 M NH4Cl were 25.1, 26.4, and 33.2 W/m2,
respectively. The increase in the NaCl dose concentration resulted in an increase
in the maximum power density and current density. A dose above 0.05 M KH2PO4
resulted in the decrease of the maximum power densities. However, when the dose
was below 0.05 M KH2PO4, the maximum power density increased with the increase in
KH2PO4 dose.
PMID- 29331909
TI - Linking composition of extracellular polymeric substances (EPS) to the physical
structure and hydraulic resistance of membrane biofilms.
AB - The effect of extracellular polymeric substances (EPS) on the meso-scale physical
structure and hydraulic resistance of membrane biofilms during gravity driven
membrane (GDM) filtration was investigated. Biofilms were developed on the
surface of ultrafiltration membranes during dead-end filtration at ultra-low
pressure (70 mbar). Biofilm EPS composition (total protein, polysaccharide and
eDNA) was manipulated by growing biofilms under contrasting nutrient conditions.
Nutrient conditions consisted of (i) a nutrient enriched condition with a
nutrient ratio of 100:30:10 (C: N: P), (ii) a phosphorus limitation (C: N: P
ratio: 100:30:0), and (iii) a nitrogen limitation (C: N: P ratio: 100:0:10). The
structure of the biofilm was characterised at meso-scale using Optical Coherence
Tomography (OCT). Biofilm composition was analysed with respect to total organic
carbon, total cellular mass and extracellular concentrations of proteins,
polysaccharides, and eDNA. 2D-confocal Raman mapping was used to characterise the
functional group composition and micro-scale distribution of the biofilms EPS.
Our study reveals that the composition of the EPS matrix can determine the meso
scale physical structure of membrane biofilms and in turn its hydraulic
resistance. Biofilms grown under P limiting conditions were characterised by
dense and homogeneous physical structures with high concentrations of
polysaccharides and eDNA. Biofilm grown under nutrient enriched or N limiting
conditions were characterised by heterogeneous physical structures with lower
concentrations of polysaccharides and eDNA. For P limiting biofilms, 2D-confocal
Raman microscopy revealed a homogeneous spatial distribution of anionic
functional groups in homogeneous biofilm structures with higher polysaccharide
and eDNA concentrations. This study links EPS composition, physical structure and
hydraulic resistance of membrane biofilms, with practical relevance for the
hydraulic performances of GDM ultrafiltration.
PMID- 29331910
TI - Review of synthetic human faeces and faecal sludge for sanitation and wastewater
research.
AB - Investigations involving human faeces and faecal sludge are of great importance
for urban sanitation, such as operation and maintenance of sewer systems, or
implementation of faecal sludge management. However, working with real faecal
matter is difficult as it not only involves working with a pathogenic, malodorous
material but also individual faeces and faecal sludge samples are highly
variable, making it difficult to execute repeatable experiments. Synthetic faeces
and faecal sludge can provide consistently reproducible substrate and alleviate
these challenges. A critical literature review of simulants developed for various
wastewater and faecal sludge related research is provided. Most individual
studies sought to develop a simulant representative of specific physical,
chemical, or thermal properties depending on their research objectives. Based on
the review, a suitable simulant can be chosen and used or further developed
according to the research needs. As an example, the authors present such a
modification for the development of a simulant that can be used for investigating
the motion (movement, settling and sedimentation) of faeces and their physical
and biological disintegration in sewers and in on-site sanitation systems.
PMID- 29331911
TI - Enhanced photocatalytic degradation of sulfamethoxazole by zinc oxide
photocatalyst in the presence of fluoride ions: Optimization of parameters and
toxicological evaluation.
AB - The presence of antibiotics in water bodies has received increasing attention
since they are continuously introduced and detected in the environment and may
cause unpredictable environmental hazards and risks. The photocatalytic
degradation of sulfamethoxazole (SMX) by ZnO in the presence of fluoride ions (F
ZnO) was evaluated. The effects of operating parameters on the efficiency of SMX
removal were investigated by using response surface methodology (RSM). Under the
optimum condition, i.e. photocatalyst dosage = 1.48 g/L, pH 4.7, airflow rate =
2.5 L/min and the concentration of fluoride ions = 2.505 mM, about 97% SMX
removal was achieved by F-ZnO after 30 min of reaction. The mechanism of
reactions, COD removal efficiency and reaction kinetics were also investigated
under optimum operating conditions. In addition, about 85% COD reduction was
obtained after 90 min photocatalytic reaction. The pseudo-first-order kinetics
rate constants for the photodegradation of SMX were found to be 0.099, 0.058 and
0.048 min-1 by F-ZnO, ZnO and TiO2 (P25), respectively. The figure-of-merit
electrical energy per order (EEO) was used for estimating the electrical energy
efficiency, which was shown to be considerably lower than the energy consumption
for the reported research on removal of SMX by photocatalytic degradation under
UV irradiation. Toxicity assays were conducted by measuring the inhibition
percentage (PI) towards E. coli bacteria strain and by agar well diffusion
method. The results showed that after 30 min of reaction, the toxicity of the
treated solutions by all photocatalysts fell within the non-toxic range; however,
the reduction in toxicity by F-ZnO was faster than those by ZnO and P25. Despite
the positive effects of surface fluorination of ZnO on the SMX and COD removal
and reaction kinetics, its lower stability compared to ZnO and P25 in the
repeated experiments gave rise to some doubts about its performance from a
practical point of view.
PMID- 29331912
TI - Elucidating the impacts of initial supersaturation and seed crystal loading on
struvite precipitation kinetics, fines production, and crystal growth.
AB - To reduce intra-plant nutrient cycling, and recover phosphorus (P) fertilizers
from nutrient-rich sidestreams, wastewater utilities increasingly elect to employ
struvite precipitation processes without a clear understanding of the inherent
tradeoffs associated with specific design and operating decisions. Specifically,
the impact of reactor conditions on struvite crystallization rate, and
distribution between formation of fines particles and secondary growth onto large
diameter seed crystals represent critical knowledge gaps limiting the predictive
capabilities of existing process models. In this work, the relative impacts of
initial supersaturation (Si), and seed loading, on P removal kinetics, and
struvite solids distribution were investigated. In experiments conducted at
different levels of initial supersaturation (1.7-2.4) and seed loading (0-25 g L
1), struvite fines represented the majority of phosphate solids formed in 10 of
12 conditions. While total P removal was dependent on Si, and primarily
attributed to formation of fines, the concentration of struvite seed granules had
a significant impact on the rate of P removal. Struvite seed granules increased
the rate of precipitation by reducing induction time of primary nucleation of
struvite fines. Secondary crystal growth represented the majority of struvite
solids formed at high seed loading and low Si, but presented the tradeoff of low
total removal and low rate of removal. To convey the significance of these
findings on process modeling, we show how a prominent kinetic model with a first
order dependency on solid struvite concentration over-predicts P removal rate
when total mass is dominated by large diameter seeds (0.9 mm). This works reveals
the critical role of struvite fines in P removal, and highlights the need to
account for their production and kinetic importance in struvite process design
and operation.
PMID- 29331913
TI - Speciation evolution of zinc and copper during pyrolysis and hydrothermal
carbonization treatments of sewage sludges.
AB - Thermal and hydrothermal treatments are promising techniques for sewage sludge
management that can potentially facilitate safe waste disposal, energy recovery,
and nutrient recovery/recycling. Content and speciation of heavy metals in the
treatment products affect the potential environmental risks upon sludge disposal
and/or application of the treatment products. Therefore, it is important to study
the speciation transformation of heavy metals and the effects of treatment
conditions. By combining synchrotron X-ray spectroscopy/microscopy analysis and
sequential chemical extraction, this study systematically characterized the
speciation of Zn and Cu in municipal sewage sludges and their chars derived from
pyrolysis (a representative thermal treatment technique) and hydrothermal
carbonization (HTC; a representative hydrothermal treatment technique).
Spectroscopy analysis revealed enhanced sulfidation of Zn and Cu by anaerobic
digestion and HTC treatments, as compared to desulfidation by pyrolysis. Overall,
changes in the chemical speciation and matrix properties led to reduced mobility
of Zn and Cu in the treatment products. These results provide insights into the
reaction mechanisms during pyrolysis and HTC treatments of sludges and can help
evaluate the environmental/health risks associated with the metals in the
treatment products.
PMID- 29331914
TI - Pore diffusion limits removal of monochloramine in treatment of swimming pool
water using granular activated carbon.
AB - Overall apparent reaction rates for the removal of monochloramine (MCA) in
granular activated carbon (GAC) beds were determined using a fixed-bed reactor
system and under conditions typical for swimming pool water treatment. Reaction
rates dropped and quasi-stationary conditions were reached quickly. Diffusional
mass transport in the pores was shown to be limiting the overall reaction rate.
This was reflected consistently in the Thiele modulus, in the effect of
temperature, pore size distribution and of grain size on the reaction rates.
Pores <2.5 times the diameter of the monochloramine molecule were shown to be
barely accessible for the monochloramine conversion reaction. GACs with a
significant proportion of large mesopores were found to have the highest overall
reactivity for monochloramine removal.
PMID- 29331915
TI - Theory of water treatment by capacitive deionization with redox active porous
electrodes.
AB - Capacitive deionization (CDI) for water treatment, which relies on the capture of
charged species to sustain the electrical double layers (EDLs) established within
porous electrodes under an applied electrical potential, can be enhanced by the
chemical attachment of fixed charged groups to the porous electrode electrodes
(ECDI). It has recently been demonstrated that further improvements in capacity
and energy storage can be gained by functionalization of the electrode surfaces
with redox polymers in which the charge on the electrodes can be modulated
through Faradaic reactions under different cell voltages in a capacitive process
that can be called "Faradaic CDI" (FaCDI). Here, we extend recent mathematical
models developed for the characterization of CDI and ECDI systems to incorporate
the redox mediated contributions by allowing for the variable chemical charges
generated by reactions in FaCDI. The lumped model developed here assumes the
spacer channel is well-mixed with uniform electrosorption in each electrode. We
demonstrate that the salt adsorption performance characterization of the fixed
chemical charge ECDI and variable chemical charge FaCDI materials can be unified
within a common theoretical framework based on the point of zero charge (PZC) of
the electrode material. In the latter case the PZC is determined by the
equilibrium potentials of the redox couples immobilized on the porous electrodes.
The new model is able to predict the experimentally observed enhanced and
inverted performance of CDI cells, and illuminates the benefit of choosing redox
active materials for water treatment applications. The deionization performance
of FaCDI cells is shown to be superior to that of CDI and ECDI systems with
equilibrium adsorption capacities 50-100% higher than attained with CDI systems,
and at smaller cell voltages, depending on the redox potentials of the Faradaic
moieties.
PMID- 29331916
TI - Aerobic exercise is more effective than goal-based exercise for the treatment of
cognition in Parkinson's disease.
AB - BACKGROUND: Little is known about how different exercise modalities influence
cognition in Parkinson's disease (PD). Moreover, the focus of previous
investigations on examining the effects of exercise mainly on executive functions
and the exclusion of individuals with cognitive impairment may limit the
potential to define exercise as a treatment for cognitive decline in PD.
OBJECTIVE: The aim of this study was to compare the effects of aerobic and goal
based exercise on five cognitive domains in cognitively normal and impaired
individuals with PD. METHODS: Seventy-six individuals with PD were randomly
allocated into three groups: Aerobic, Goal-based, and Control. Participants in
the exercise groups attended 1-h sessions 3x/week for 12 weeks, while those in
the Control group carried on with their regular activities. Changes in cognitive
domains were assessed using paper-based neuropsychological tests. RESULTS:
Inhibitory control improved only in the Aerobic group (p = .04), irrespective of
participants cognitive status at baseline. Moreover, participants with cognitive
impairment in Aerobic group maintained their set-shifting ability, whereas those
in the Control group were worse at post-test (p = .014). CONCLUSION: This is the
first study to show that aerobic exercise is more effective than goal-based
exercise for the treatment of cognition in PD with and without cognitive
impairment.
PMID- 29331917
TI - Comparision of photocatalysis and photolysis processes for arsenic oxidation in
water.
AB - The oxidation of As(III) to As(V) in aqueous solution was evaluated using
heterogeneous photocatalysis and photolysis. The influence of TiO2 as catalyst in
different crystalline (rutile, anatase) and commercial forms was evaluated in a
batch reactor and an insignificant difference was observed between them. The
process by photocatalysis reached up to 97% As(III) oxidation and no significant
difference was observed comparing to results obtained by photolysis. The
photolysis experiments (UV radiation only), also carried out in a batch system,
showed a high oxidation rate of As(III) (90% in 20min). The influence of
different matrices (well water, river water and public water supply) were
evaluated. Additionally, the effect of As(V) concentration, generated during the
oxidation process, was studied. Continuous photolysis experiments using only UV
radiation were performed, resulting in a high As(III) oxidation rate. Using a
flow rate of 5mLmin-1 and an initial concentration of As(III) 200ugL-1, gave an
oxidation percentage of As(III) of up to 72%, showing a simple and economical
alternative to the oxidation step of As(III) to As(V) in the treatment of water
contaminated with arsenic.
PMID- 29331918
TI - DNA damage in marine rock oyster (Saccostrea Cucullata) exposed to
environmentally available PAHs and heavy metals along the Arabian Sea coast.
AB - Molecular biomarkers are used world wide for quick assessment of the immediate
effect of environmental pollution on marine ecosystems. Recently, we evaluated
oxidative stress responses of marine rock oyster, Saccostrea cucullata impacted
due to polycyclic aromatic hydrocarbons (PAHs) accumulated in their tissues at a
few sampling sites along the coast of Goa around the region of the Arabian sea
coast, India (Sarkar et al., 2017). Using a combination of partial alkaline
unwinding and comet assays, we now report a comprehensive study on the impairment
of DNA integrity (DI) in S. cucullata due to exposure to environmentally
available PAHs and also heavy metals (Pb, Cd, Cu, Fe and Mn) along the Arabian
Sea coast, Goa, India exclusively around the entire coast of Goa. First, we
determined significant correlation between DI in S. cucullata and the extent of
exposure to and bioaccumulation of different PAH compounds including 2-3 aromatic
ring PAHs (R2, 0.95), 4-6 aromatic ring PAHs (R2, 0.85), oxygenated-PAHs (oxy
PAHs, R2, 0.84) and total PAHs (t-PAHs, R2, 0.98). Second, we observed dose
dependent decrease in DI in S. cucullata with increasing concentrations of
different PAH components in oyster tissues. We substantiated our field
observations with appropriate laboratory controls using benzo[a]pyrene (BaP).
Third, we performed stepwise multiple regression analyses of different water
quality parameters including pH, salinity, temperature, dissolved oxygen (DO),
biochemical oxygen demand (BOD), nitrite (NO2), nitrate (NO3), phosphate (PO4),
turbidity and also t-PAH-biota, t-PAH-water with DI as the dependent variable.
Among all these parameters, only four parameters such as t-PAH-biota in
combination with DO, BOD and NO2 showed significant correlation (R-2 = 0.95) with
loss in DI in S. cucullata. Based on these results, we created a map indicating
the percentage of DNA damage in S. cucullata exposed to PAHs and heavy metals at
each sampling location along the west coast of India around Goa, India.
PMID- 29331919
TI - Removal of pharmaceutical pollutants from synthetic wastewater using chemically
modified biomass of green alga Scenedesmus obliquus.
AB - Pharmaceutical compounds are considered emerging environmental pollutants that
have a potential harmful impact on environment and human health. In this study,
the biomass of alga (Scenedesmus obliquus) was modified using alkaline solution,
and used for the biosorption of tramadol (TRAM) and other pharmaceuticals. The
adsorption kinetics and isotherms were investigated. The obtained results reveal
high adsorption capacity of tramadol over modified algal biomass (MAB) after
45min with removal percentage of 91%. Pseudo-second order model was well fitted
with the experimental data with correlation coefficient (0.999). Biosorption of
tramadol on modified algal biomass proceeds with Freundlich isotherm model with
correlation coefficient (0.942) that emphasized uptake of TRAM by MAB is driven
by chemisorption. FTIR spectra of MAB before and after the adsorption were
analyzed; some IR bands were detected with slight shift and low intensity
suggesting their involving in adsorption. The tramadol biosorption by MAB is a
chemical process as confirmed by Dubinin-Radushkevich. The adsorption of
pharmaceutical over MAB is mainly preceded by hydrophilic interactions between
amino and carbonyl groups in pharmaceutical molecules and hydroxyl and carbonyl
functional groups on surface of biosorbent. It was emphasized by disappearance O
H and C-O from biomass IR spectra after adsorption. In matrix of pharmaceutical,
the recorded adsorption capacities for CEFA, PARA, IBU, TRAM and CIP are 68, 58,
42, 42 and 39mg/g over MAB at natural pH and MAB dose of 0.5g/L. Furthermore,
oxygen uptake by bacteria was applied for estimate the toxicity of
pharmaceutical. The recorded result concluded the efficient reusability of
modified algal biomass for biosorption of pharmaceuticals, as well only the
adsorption efficiency decreased by 4.5% after three runs. Subsequently, the
modified algal biomass is a promising reusable adsorbent for decontamination of
wastewater from pharmaceuticals.
PMID- 29331920
TI - Engineering yeast for utilization of alternative feedstocks.
AB - Realizing the economic benefits of alternative substrates for commodity chemical
bioproduction typically requires significant metabolic engineering of common
model organisms, such as Saccharomyces cerevisiae. A growing toolkit is enabling
engineering of non-conventional yeast that have robust native metabolism for
xylose, acetate, aromatics, and waste lipids. Scheffersomyces stipitis was
engineered to produce itaconic acid from xylose. Yarrowia lipolytica produced
lipids from dilute acetate at over 100g/L. Cutaneotrichosporon oleaginosus was
engineered to produce omega-3 fatty acids and recently was shown to accumulate
nearly 70% lipids when grown on aromatics as a carbon source. Further improvement
to toolkits for genetic engineering of non-conventional yeast will enable future
development of alternative substrate conversion to biochemicals.
PMID- 29331921
TI - Cyclotron production of 99mTc: Comparison of known separation technologies for
isolation of 99mTc from molybdenum targets.
AB - Intensive efforts were undertaken during the last few decades for the separation
of cyclotron-produced 99mTc from 99Mo and new papers have been published on this
topic since the last review [1]. In the future the cyclotron-based methods can
replace reactor-based technology in producing this medical radioisotope and the
nuclear reaction 100Mo(p,2n)99mTc appears to be the most worthwhile approach. New
ways of producing of 99mTc require efficient separation methods. Several
strategies for separation of 99mTc from 99Mo have been already developed. The
advantages, disadvantages and technical challenges toward application potential
of investigated methods to separate 99mTc from irradiated 100Mo target are
discussed. These methods include column chromatography, solvent extraction,
chemical precipitation and thermochromatography.
PMID- 29331922
TI - Minimum alveolar concentration: Key concepts and a review of its pharmacological
reduction in dogs. Part 1.
AB - OBJECTIVE: To outline the major components of the minimum alveolar concentration
(MAC) and review the literature in regard to pharmacological manipulation of the
MAC of halothane, isoflurane, sevoflurane, enflurane, and desflurane in dogs. The
pharmacologic agents included are alpha-2 agonists, benzodiazepines, propofol,
maropitant, opioids, lidocaine, acepromazine, non-steroidal anti-inflammatory
agents, and NMDA antagonists. Part 1 will focus on summarizing the relevance,
measurement, and mechanisms of MAC and review the effects of alpha-2 agonists,
benzodiazepines, and propofol on MAC. DATABASES USED: PubMed, Google Scholar, CAB
Abstracts. Search terms used: minimum alveolar concentration, MAC, dog, canine,
inhaled anesthetic potency, isoflurane, sevoflurane, desflurane, enflurane, and
halothane. CONCLUSIONS: Many drugs reduce the MAC of inhaled anesthetics in dogs,
and allow for a clinically important decrease in inhalant anesthetic use. A
decrease in MAC may decrease the adverse cardiovascular and pulmonary effects
associated with the use of high concentrations of inhaled anesthetics.
PMID- 29331923
TI - Cold-regulated protein (SlCOR413IM1) confers chilling stress tolerance in tomato
plants.
AB - Chilling stress severely affects the growth, development and productivity of
crops. Chloroplast, a photosynthesis site, is extremely sensitive to chilling
stress. In this study, the functions of a gene encoding a cold-regulated protein
(SlCOR413IM1) under chilling stress were investigated using sense and antisense
transgenic tomatoes. Under chilling stress, SlCOR413IM1 expression was rapidly
induced and the sense lines exhibited better growth state of seedlings and grown
tomato plants. Overexpression of SlCOR413IM1 alleviated chilling-induced damage
to the chloroplast membrane and structure, whereas suppression of SlCOR413IM1
aggravated the damage to chloroplast. Moreover, the net photosynthetic rate (Pn),
maximum photochemical efficiency of photosystem II (PSII) (Fv/Fm), actual
photochemical efficiency of PSII (PhiPSII) and the activities of glyceraldehyde-3
phosphate dehydrogenase (GAPDH) and stromal fructose-1, 6-bisphosphatase
(sFBPase) were higher in the sense lines than those in the antisense lines.
Hence, the inhibition of photosynthetic capacity was less severe in the sense
lines but more severe in the antisense lines compared with that in wild-type (WT)
plants. Taken together, overexpression of SlCOR413IM1 enhanced the chilling
stress tolerance, whereas suppression of this gene increased the chilling
sensitivity of tomato plants.
PMID- 29331924
TI - Gene expression patterns regulating the seed metabolism in relation to
deterioration/ageing of primed mung bean (Vigna radiata L.) seeds.
AB - We are proposing mechanisms to account for the loss of viability (seed
deterioration/ageing) and enhancement in seed quality (post-storage priming
treatment). In order to understand the regulatory mechanism of these traits, we
conducted controlled deterioration (CD) test for up to 8 d using primed mung bean
seeds and examined how CD effects the expression of many genes, regulating the
seed metabolism in relation to CD and priming. Germination declined progressively
with increased duration of CD, and the priming treatment completely/partially
reversed the inhibition depending on the duration of CD. The loss of germination
capacity by CD was accompanied by a reduction in total RNA content and RNA
integrity, indicating that RNA quantity and quality impacts seed longevity.
Expression analysis revealed that biosynthesis genes of GA, ethylene, ABA and ROS
scavenging enzymes were differentially affected in response to duration of CD and
priming, suggesting coordinately regulated mechanisms for controlling the
germination capacity of seeds by modifying the permeability characteristics of
biological membranes and activities of different enzymes. ABA genes were highly
expressed when germination was delayed and inhibited by CD. Whereas, GA and
ethylene genes were more highly expressed when germination was enhanced and
permitted by priming under similar conditions. GSTI, a well characterized enzyme
family involved in stress tolerance, was expressed in primed seeds over the
period of CD, suggesting an additional protection against deterioration. The
results are discussed in light of understanding the mechanisms underlying
longevity/priming which are important issues economically and ecologically.
PMID- 29331925
TI - Overexpression of Chrysanthemum lavandulifolium ClCBF1 in Chrysanthemum
morifolium 'White Snow' improves the level of salinity and drought tolerance.
AB - This paper reports the first study on plant CBF transcription factors (TF) in
salt and drought stress responses in Chrysanthemum lavandulifolium. A CBF homolog
gene, named as ClCBF1, from C. lavandulifolium was isolated using rapid
amplification of cDNA ends (RACE). The deduced peptide is comprised of 210 amino
acids (AA) containing an AP2 structural domain characteristic of the AP2 gene
family. Quantitative real-time PCR revealed that ClCBF1 gene exhibit differential
expression patterns across root, leaf and stem tissues, and it was strongly
induced under salt and drought treatments of C. lavandulifolium. Overexpression
of ClCBF1 in C. morifolium 'White Snow' resulted in stronger tolerance to salt
and drought stresses. The ClCBF1 expression level, enzymatic activities of
superoxide dismutase and peroxidase, and contents of proline and soluble proteins
were enhanced in these transgenic lines, they were repressed in the antisense
transgenic lines under the same stress conditions. Results indicate that ClCBF1
represents a promising candidate gene in improving abiotic stress tolerance among
ornamental plants.
PMID- 29331926
TI - Two hump-shaped angular distributions of neutrons and soft X-rays in a small
plasma focus device.
AB - Angular distributions of soft X-rays (SXRs) and neutrons emitted by a small
plasma focus device (PFD) were investigated simultaneously using TLD-100
dosimeters and Geiger-Muller activation counters, respectively. The distributions
represented two humps with a small dip at the angular position 0 degrees and
reduced from the angles of +/- 15 degrees and +/- 30 degrees for the neutrons
and SXRs, respectively. The maximum yield of 2.98 * 108 neutrons per shot of the
device was obtained at 13.5kV and 6.5mbar. A time of flight (TOF) of 75.2ns
between the hard X-ray and the neutron peaks corresponds to neutrons with energy
of 2.67MeV. A similar behavior was observed between the angular distributions of
neutron and soft X-ray emissions.
PMID- 29331927
TI - Honeycomb-like polysulphone/polyurethane nanofiber filter for the removal of
organic/inorganic species from air streams.
AB - Nanofiber nonwoven filters, especially those prepared by electrospinning, are of
particular interest because of their high filtration efficiency. However,
existing electrospun filters suffer from inherent limitations in that both
strengths and filtration resistances of the filters leave much to be desired.
Herein, we present a novel nonwoven filter that is composed of polysulphone and
polyurethane nanofibers. By mimicking the honeycomb structure, a heterogeneous
distribution of both fiber diameter and fiber density has been achieved. Compared
with nanofiber nonwovens with plain architectures, the honeycomb-like nonwovens
possess higher filtration efficiency (~99.939%), better mechanical strength
(~105.24 N g-1) and improved quality factor (~0.04 Pa-1). The filtration
efficiency against both inorganic and organic aerosols is guaranteed through the
nanofiber surface geometry and the intrinsic charge-retention capacity of
polysulphone. Since the production of this nanofiber filter does not need
multistep procedures and can be easily scaled up on a needleless electrospinning
device, we anticipate that the strategy of endowing nanofibers with honeycomb
texture and charge-retention capacity may lead to the development of advanced
fiber filters.
PMID- 29331928
TI - Being in control? A thematic content analysis of 14 in-depth interviews with 2,4
dinitrophenol users.
AB - BACKGROUND: 2,4-Dinitrophenol (2,4-DNP) is a compound with multiple industrial
purposes. Currently unlicensed for human consumption, it is used by the gym-going
population for drastic, short-term body fat loss. Nonetheless, physiological
mechanisms can lead to potentially fatal hyperthermia. Reported fatal incidents
have caused concern and highlighted the need for intervention. Understanding
decision-making leading to 2,4-DNP use alongside the perceived outgroup attitudes
is vital to forming effective harm minimisation policies targeting current and
potential users. First-hand accounts from this elusive population are scarce.
METHODS: Fourteen novel and experienced users (13 male, 1 female) were recruited
via "snowballing" techniques. Semi-structured interviews were conducted,
comprising 28 questions. Thematic content analysis was conducted using 37 codes.
RESULTS: Four characteristic themes emerged: 1. Users considered the Internet to
be a crucial multifunctional resource directly impacting their 2,4-DNP use. 2.
Users "respected" 2,4-DNP, proactively taking harm reduction measures. 3.
Attitudinal polarisation towards 2,4-DNP within the gym-going community was
consistent in all accounts. 4. Users perceived outgroup populations to have
inherently negative attitudes towards their use. These themes fell under the all
encompassing theme of "being in control". CONCLUSION: For the first time, this
study offers a rich detail of attitudes toward 2,4-DNP use by giving a collective
voice to users. The element of control over every aspect of the users' life
appears to be a significant contributor to the successful risk-management of 2,4
DNP use. In the absence of an established safe upper limit and effective
regulatory control, education is critical to harm minimisation.
PMID- 29331929
TI - Sex-related differential response to dexamethasone in endocrine and immune
measures in depressed in-patients and healthy controls.
AB - Although sex differences in major depression have been reported repeatedly, the
underlying mechanisms are still disputed. The rapidly changing gonadal steroid
concentrations of the postpartum period or during menopause have been shown to be
associated with depressive symptoms and to modulate the hypothalamic-pituitary
adrenal (HPA)-axis, which is implicated in depression. The sample comprised of
128 depressed in-patients (36.7% women) and 166 healthy controls (30.0% women).
Blood was collected at baseline (at 6pm) and then 3 h as well as 21 h after
ingestion of 1.5 mg dexamethasone for measurement of cortisol, ACTH and blood
count. To further assess the function of the HPA-axis the
dexamethasone/corticotrophin releasing hormone (Dex-CRH) test was performed in a
subsample of 115 patients and 116 controls the following day. A significant
interaction effect between sex, disease and ACTH concentrations over time after
dexamethasone stimulation was observed, with men showing increased ACTH
concentrations at baseline and after 21 h, while there was no difference after 3
h (p = .007). After separating for disease status this significant interaction
effect was only observed in controls (p = .005). The cortisol response in the dex
CRH test was enhanced in female compared to male controls (p = .002). Leucocytes
showed a stronger increase upon dexamethasone administration only in female
compared to male controls (p = .023). These findings suggest a higher
glucocorticoid receptor sensitivity following in-vivo glucocorticoid stimulation
in healthy women that was absent in depressed patients. The sex-related
differences in HPA-axis regulation and immune system function may contribute to
the vulnerability of female sex to the development of depression.
PMID- 29331930
TI - Sleep quality, psychological symptoms, and psychotic-like experiences.
AB - Poor sleep quality has been repeatedly linked to the entire psychosis continuum,
including psychotic-like experiences (PLEs); however, sleep dysfunction is a
component of several other psychopathologies that have also been linked to
increased risk for PLEs, including depression, anxiety, and post-traumatic stress
disorder (PTSD). It has yet to be examined if PLEs are a significant risk factor
for poor sleep quality or if this sleep dysfunction is better accounted for by
comorbid psychopathology. In 2687 undergraduates, PLEs were evaluated using the
positive items of the Prodromal Questionnaire. Symptoms of anxiety, depression,
and PTSD were also assessed, as was sleep quality. Mediation analysis using
PROCESS was conducted to determine if poor sleep quality associated with PLEs was
in fact more associated with symptoms of other psychopathologies. Symptoms of
depression and PTSD mediated the relationship between PLEs and sleep quality,
though anxiety symptoms did not. These findings suggest that treating symptoms of
depression and PTSD may improve multiple domains of psychotic illness.
PMID- 29331931
TI - Resting-state fMRI signals in offspring of parents with bipolar disorder at the
high-risk and ultra-high-risk stages and their relations with cognitive function.
AB - BACKGROUND: Bipolar disorder (BD) has been associated with dysfunctional resting
state brain functioning. However, it is still not known whether the aberrant
functioning occurs and predict cognitive functioning before illness onset. AIMS:
We examined the resting-state regional and network dysfunctioning, and their
correlates with neurocognitive performance, in the high-risk (HR) and ultra-high
risk (UHR) stages of bipolar disorder. METHODS: Using amplitude of low-frequency
fluctuations (ALFF), region homogeneity (ReHo) and hypothesis-driven region-of
interest (ROI)-based connectivity, we examined resting-state fMRI data of 8- to
25-year-old healthy offspring (HR, n = 28) and offspring with subthreshold
syndromes (UHR, n = 22) of a BD parent, and age-matched healthy controls without
any personal or family psychopathology (HC, n = 46). Participants' neurocognitive
profiles were assessed using the MATRICS Consensus Cognitive Battery (MCCB).
RESULTS: ALFF signals in the left putamen and right rolandic operculum were lower
in the HR group compared to the HC group. In contrast, ALFF signals were
increased in the UHR group in the right middle pars orbitalis of the inferior
frontal gyrus, right calcarine sulcus and right cerebellum. Connectivities
between the right amygdala and left inferior temporal gyrus, between the left
hippocampus and inferior occipital gyrus, and between the left hippocampus and
middle pars orbitalis gyrus were decreased in the HR group compared to the HC
group. In UHR versus HC group, connectivity between the right amygdala and the
left hippocampus and left insula was increased, and connectivity between the left
hippocampus and the left insula and the cerebellum was also increased. Among
cognitive measures, processing speed was positively correlated with ALFF signals
in the left putamen in the HR offspring. In the UHR offspring, processing speed,
attention, and verbal learning/memory were positively correlated with the
functional connectivity between the left hippocampus and cerebellum. CONCLUSIONS:
Offspring of parents with BD in the HR and UHR stages show largely non
overlapping patterns of atypical resting-state signals and functional
connectivity that predicted cognitive functioning, possibly reflecting inherited
abnormalities and/or complimentary reactions.
PMID- 29331932
TI - CNV biology in neurodevelopmental disorders.
AB - Copy number variants (CNVs), characterized in recent years by cutting-edge
technology, add complexity to our knowledge of the human genome. CNVs contribute
not only to human diversity but also to different kinds of diseases including
neurodevelopmental delay, autism spectrum disorder and neuropsychiatric diseases.
Interestingly, many pathogenic CNVs are shared among these diseases. Studies
suggest that pathophysiology of disease may not be simply attributed to a single
driver gene within a CNV but also that multifactorial effects may be important.
Gene expression and the resulting phenotypes may also be affected by epigenetic
alteration and chromosomal structural changes. Combined with human genetics and
systems biology, integrative research by multi-dimensional approaches using
animal and cell models of CNVs are expected to further understanding of
pathophysiological mechanisms of neurodevelopmental disorders and
neuropsychiatric disorders.
PMID- 29331933
TI - Combined effects of Ag and UiO-66 for removal of elemental mercury from flue gas.
AB - The zirconium metal-organic framework material UiO-66 was doped with Ag
nanoparticles and investigated for the removal of elemental mercury (Hg0) in flue
gas. Physical and chemical characterization of the adsorbents showed that adding
Ag did not change the crystal structure and morphology of the UiO-66. Ag doping
can improve the redox activity of UiO-66, and the adsorbent exhibited high
thermal stability and surface area. Hg0 removal experiments indicated that UiO-66
exhibited the higher performance compared with P25 and activated carbon, and the
addition of Ag exhibited a significant synergistic effect with the UiO-66, which
had highest Hg0 adsorption capacity (3.7 mg/g) at 50 degrees C. Furthermore, the
Hg0 removal mechanism was investigated, revealing that Hg0 is removed by the
formation of an Ag amalgam and channel adsorption at low temperature, and through
Ag-activated oxygen oxidation and channel capture at high temperature.
PMID- 29331934
TI - Characterization and release profile of (Mn, Al)-bearing deposits in drinking
water distribution systems.
AB - Inorganic contaminants accumulation in drinking water distribution systems (DWDS)
is a great threat to water quality and safety. This work assessed the main risk
factors for different water pipes and discovered the release profile of
accumulated materials in a full scale distribution system frequently suffered
from water discoloration problem. Physicochemical characterization of pipe
deposits were performed using X-ray fluorescence, scanning electron microscopy, X
ray diffraction, X-ray photoelectron spectroscopy and Fourier transform infrared
spectroscopy. The metal release profile was obtained through continuous
monitoring of a full-scale DWDS area. The results showed that aluminum and
manganese were the main metals of deposits in nonmetallic pipes, while iron was
dominant in iron-based pipe corrosion scales. Manganese primarily existed as MnO2
without well crystalline form. The relative abundance of Mn and Fe in deposits
changed with their distance from the water treatment plant. Compared with iron in
corrosion scales, Mn and Al were more labile to be released back into bulk water
during unidirectional flushing process. A main finding of this work is the co
release behavior of Mn and Al in particulate form and significant correlation
exists between these two metals. Dual control of manganese and aluminum in
treated water is proposed to be essential to cope with discoloration and trace
metal contamination in DWDS.
PMID- 29331936
TI - Influence of custom foot orthoses on venous status: A quasi-experimental study.
AB - BACKGROUND: Customized foot orthoses (CFO) have been widely accepted to reduce
the frequency of foot problems and postural disorders. The purpose of the
research was to compare the influence of CFO utilization on the venous status
among healthy females and males. METHODS: This was a quasi-experimental study
(NCT03329430), which included 20 healthy subjects that completed all the stages
of the process. The subjects showed an age mean of 20.00 +/- 1.62 years and were
recruited in a foot and ankle specialist center. Self-reported data were medical
records and venous function which were evaluated by plethysmography with or
without utilization of CFO. RESULTS: A sample of 40 feet was studied, showing
statistically significant differences between venous filling time (P < 0.001) and
in the ejection fraction (P < 0.001) with CFO utilization versus without use of
CFO. CONCLUSIONS: Healthy people who utilize CFO evidenced an increased venous
return in the feet.
PMID- 29331935
TI - Disruption of thyroid hormone sulfotransferase activity by brominated flame
retardant chemicals in the human choriocarcinoma placenta cell line, BeWo.
AB - Brominated flame retardants (BFRs) have been shown to disrupt thyroid hormone
(TH) homeostasis through multiple mechanisms, including inhibition of enzymes
that regulate intracellular levels of THs, such as sulfotransferases (SULTs). The
placenta plays a critical role in helping to maintain TH levels during fetal
development and expresses SULTs. This is concerning given that disruption of TH
regulation within the placenta could potentially harm the developing fetus. In
this study, we investigated the effects of two polybrominated diphenyl ethers
(PBDEs), two hydroxylated PBDEs, and 2,4,6-tribromophenol (2,4,6-TBP) on TH SULT
activity in a choriocarcinoma placenta cell line (BeWo). BeWo cells were exposed
to BFR concentrations up to 1 MUM for 1-24 h to investigate changes in basal SULT
activity and in mRNA expression of several TH regulating genes. 2,4,6-TBP was the
most potent inhibitor of basal 3,3'-T2 SULT activity at all exposure durations,
decreasing activity by as much as 86% after 24 h of exposure. BDE-99, 3-OH BDE
47, and 6-OH BDE-47 also decreased 3,3'-T2 SULT activity by 23-42% at
concentrations of 0.5 MUM and 1.0 MUM following 24 h exposures. BDE-47 had no
effect on SULT activity, and there was no observed effect of any BFR exposure on
expression of SULT1A1, or thyroid nuclear receptors alpha or beta. This research
demonstrates that total TH SULT activity in placental cells are sensitive to BFR
exposure; however, the mechanisms and consequences have yet to be fully
elucidated.
PMID- 29331937
TI - Quasi-static tensile properties of the Cranial Cruciate Ligament (CrCL) in adult
cattle: towards the design of a prosthetic CrCL.
AB - Mechanical properties of the Cranial Cruciate Ligament (CrCL) in adult cattle are
not well documented and protocols used in the literature focus on testing a full
femur-CrCL-tibia complex rather than an isolated CrCL. The aim of this study was
to assess a wider range of tensile properties of the CrCL along its anatomic axis
with experimental measurements of the global elongation, displacement and strain
fields, in order to provide guidelines for the design of CrCL prosthetic
surrogates. Fourteen bovine CrCL were harvested from seven mature cows (5.1 +/-
1.3 years) weighing 631 +/- 90kg. The mean CrCL length was 41.4 +/- 1.5mm and its
mean cross-section was 103.9 +/- 23.8mm2. Pre-conditioning was achieved with 30
cycles of loading from 30 to 200N at a strain rate of 0.02s-1. Specimens were
then loaded to failure at the same strain rate. The following results were
obtained: the mean ultimate tensile load (UTL) 4372 +/- 1485N and the median
[quartiles] maximal global elongation 19.3 [17.8; 21.4] %. At first physical
signs of tearing, the mean load was 3315 +/- 1336N and mean elongation 13.5 +/-
4.9%. The mean absorbed energy at failure was 5.23 +/- 2.08 MJ.mm-3 and the mean
stiffness at various levels of elongation was: 220 +/- 195N.%-1 (5%), 285 +/-
162N.%-1 (10%), 239 +/- 200N.%-1 (15%), 146 +/- 59N.%-1 (20%), 153 +/- 136N.%-1
(25%). None of these properties were related to the bovine weight, age and side
of the body (p > 0.05). An ideal prosthetic surrogate should then follow these
sets of properties and the experimental data suggest that the in-vivo maximal
elongation is below 13.5%.
PMID- 29331938
TI - Generation of a human induced pluripotent stem cell line (CSC-40) from a
Parkinson's disease patient with a PINK1 p.Q456X mutation.
AB - Parkinson's disease (PD) is a neurodegenerative disease with unknown etiology.
Here we show the generation of an induced pluripotent stem cell (iPSC) line,
named CSC-40, from dermal fibroblasts obtained from a 59-year-old male patient
with a homozygous p.Q456X mutation in the PTEN-induced putative kinase 1
(PINK/PARK6) gene and a confirmed diagnosis of PD, which could be used to model
familial PD. A non-integrating Sendai virus-based delivery of the reprogramming
factors OCT3/4, SOX2, c-MYC and KLF4 was employed. The CSC-40 cell line showed
normal karyotyping and fingerprinting following transduction as well as sustained
expression of several pluripotency markers and the ability to differentiate into
all three germ layers.
PMID- 29331939
TI - Volumetric muscle loss injury repair using in situ fibrin gel cast seeded with
muscle-derived stem cells (MDSCs).
AB - Volumetric muscle defect, caused by trauma or combat injuries, is a major health
concern leading to severe morbidity. It is characterized by partial or full
thickness loss of muscle and its bio-scaffold, resulting in extensive fibrosis
and scar formation. Therefore, the ideal therapeutic option is to use stem cells
combined with bio-scaffolds to restore muscle. For this purpose, muscle-derived
stem cells (MDSCs) are a great candidate due to their unique multi-lineage
differentiation potential. In this study, we evaluated the regeneration potential
of MDSCs for muscle loss repair using a novel in situ fibrin gel casting. Muscle
defect was created by a partial thickness wedge resection in the tibialis
anterior (TA) muscles of NSG mice which created an average of 25% mass loss. If
untreated, this defect leads to severe muscle fibrosis. Next, MDSCs were
delivered using a novel in situ fibrin gel casting method. Our results
demonstrated MDSCs are able to engraft and form new myofibers in the defect when
casted along with fibrin gel. LacZ labeled MDSCs were able to differentiate
efficiently into new myofibers and significantly increase muscle mass. This was
also accompanied by significant reduction of fibrotic tissue in the engrafted
muscles. Furthermore, transplanted cells also contributed to new vessel formation
and satellite cell seeding. These results confirmed the therapeutic potential of
MDSCs and feasibility of direct in situ casting of fibrin/MDSC mixture to repair
muscle mass defects.
PMID- 29331940
TI - Screening and functional exploration of prothrombin Arg596 related mutations in
Chinese venous thromboembolism patients.
AB - AIMS: Dysfunctional prothrombin residue Arg596 associated mutation has been found
to precipitate venous thromboembolism (VTE). In the current study we investigated
the prevalence of Arg596 associated mutations in Chinese patients with VTE and
explored the functional impact of Arg596Gln mutation on coagulation function in
affected patients. METHODS: Prothrombin clotting activity was measured in 267
unrelated patients with unprovoked VTE. Patients with moderately decreased
activities underwent further analysis of the F2 gene. Prothrombin amidolytic
activity and antigen levels were detected in mutation carriers. Specific family
members were investigated about their VTE histories and clinical phenotypes. The
thrombin generation test (TGT) was used to evaluate thrombin function and
antithrombin resistance assay was applied to assess the extent of impaired
antithrombin inhibition of mutation carriers. RESULTS: Two heterozygous mutation
carriers of prothrombin Arg596Gln were identified, both of whom had moderately
decreased clotting activities but normal amidolytic activities and antigen
levels. Among the families of the two probands, nine out of 13 mutation carriers
experienced episodes of VTE. TGTs showed that patients had elevated endogenous
thrombin potential and prolonged start tail time. Thrombin generation could be
inhibited in the presence of thrombomodulin. The thrombin Arg596Gln variant in
patients' plasma presented strong resistance to antithrombin inhibition.
CONCLUSION: Prothrombin Arg596Gln mutation is a risk factor for Chinese patients
with VTE due to its moderately decreased clotting activity but strong resistance
to antithrombin inhibition. Prothrombin clotting activity screening and its
encoding gene sequencing should be considered in patients with VTE when other
established risk factors are absent.
PMID- 29331941
TI - Early changes in the pharmacokinetic profile of vedolizumab-treated patients with
IBD may predict response after dose optimisation.
PMID- 29331942
TI - Sucrase-isomaltase 15Phe IBS risk variant in relation to dietary carbohydrates
and faecal microbiota composition.
PMID- 29331943
TI - Modern management of perianal fistulas in Crohn's disease: future directions.
AB - Perianal fistulae in patients with Crohn's disease (CD) can be associated with
significant morbidity resulting in negative impact on quality of life. The last
two decades have seen significant advancements in the management of perianal
fistulas in CD, which has evolved into a multidisciplinary approach that includes
gastroenterologists, colorectal surgeons, endoscopists and radiologists. Despite
the introduction of new medical therapies such as antitumour necrosis factor and
novel models of care delivery, the best fistula healing rates reported with
combined medical and surgical approaches are approximately 50%. More recently,
newer biologics, cell-based therapies as well as novel endoscopic and surgical
techniques have been introduced raising new hopes that outcomes can be improved
upon. In this review, we describe the modern management and the most recent
advances in the management of complex perianal fistulising CD, which will likely
impact clinical practice. We will explore optimal use of both older and newer
biological agents, as well as new data on cell-based therapies. In addition, new
techniques in endoscopic and surgical approaches will be discussed.
PMID- 29331945
TI - Risk factors for gastric cancer: is it time to discard PPIs?
PMID- 29331944
TI - Liver sampling: a vital window into HBV pathogenesis on the path to functional
cure.
AB - In order to optimally refine the multiple emerging drug targets for hepatitis B
virus (HBV), it is vital to evaluate virological and immunological changes at the
site of infection. Traditionally liver biopsy has been the mainstay of HBV
disease assessment, but with the emergence of non-invasive markers of liver
fibrosis, there has been a move away from tissue sampling. Here we argue that
liver biopsy remains an important tool, not only for the clinical assessment of
HBV but also for research progress and evaluation of novel agents. The importance
of liver sampling has been underscored by recent findings of specialised subsets
of tissue-resident immune subsets capable of efficient pathogen surveillance,
compartmentalised in the liver and not sampled in the blood. Importantly, the
assessment of virological parameters, such as cccDNA quantitation, also requires
access to liver tissue. We discuss strategies to maximise information obtained
from the site of infection and disease pathology. Fine needle aspirates of the
liver may allow longitudinal sampling of the local virus/host landscape. The
careful utilisation of liver tissue and aspirates in conjunction with blood will
provide critical information in the assessment of new therapeutics for the
functional cure of HBV.
PMID- 29331947
TI - Response to: 'Prognosis of immune-tolerant phase chronic hepatitis B' by Chu and
Liaw.
PMID- 29331948
TI - LVIS Blue as a low porosity stent and coil adjuvant.
AB - INTRODUCTION: The LVIS Blue is an FDA-approved stent with 28% metallic coverage
that is indicated for use in conjunction with coil embolization for the treatment
of intracranial aneurysms. Given a porosity similar to approved flow diverters
and higher than currently available intracranial stents, we sought to evaluate
the effectiveness of this device for the treatment of intracranial aneurysms.
METHODS: We performed an observational single-center study to evaluate initial
occlusion and occlusion at 6-month follow-up for patients treated with the LVIS
Blue in conjunction with coil embolization at our institution using the modified
Raymond-Roy classification (mRRC), where mRRC 1 indicates complete embolization,
mRRC 2 persistent opacification of the aneurysm neck, mRRC 3a filling of the
aneurysm dome within coil interstices, and mRRC 3b filling of the aneurysm dome.
RESULTS: Sixteen aneurysms were treated with the LVIS Blue device in conjunction
with coil embolization with 6-month angiographic follow-up. Aneurysms were
treated throughout the intracranial circulation: five proximal internal carotid
artery (ICA) (ophthalmic or communicating segments), two superior cerebellar
artery, two ICA terminus, two anterior communicating artery, two distal middle
cerebral artery, one posterior inferior cerebellar artery, and two basilar tip
aneurysms. Post-procedurally, there was one mRRC 1 closure, five mRRC 2 closures,
and 10 mRRC 3a or 3b occlusion. At follow-up, all the mRRC 1 and mRRC 3a
closures, 85% of the mRRC 3b closures and 75% of the mRRC 2 closures were stable
or improved to an mRRC 1 or 2 at follow-up. CONCLUSIONS: The LVIS Blue represents
a safe option as a coil adjunct for endovascular embolization within both the
proximal and distal anterior and posterior circulation.
PMID- 29331946
TI - Management of patients on antithrombotic agents undergoing emergency and elective
endoscopy: joint Asian Pacific Association of Gastroenterology (APAGE) and Asian
Pacific Society for Digestive Endoscopy (APSDE) practice guidelines.
AB - This Guideline is a joint official statement of the Asian Pacific Association of
Gastroenterology (APAGE) and the Asian Pacific Society for Digestive Endoscopy
(APSDE). It was developed in response to the increasing use of antithrombotic
agents (antiplatelet agents and anticoagulants) in patients undergoing
gastrointestinal (GI) endoscopy in Asia. After reviewing current practice
guidelines in Europe and the USA, the joint committee identified unmet needs,
noticed inconsistencies, raised doubts about certain recommendations and
recognised significant discrepancies in clinical practice between different
regions. We developed this joint official statement based on a systematic review
of the literature, critical appraisal of existing guidelines and expert consensus
using a two-stage modified Delphi process. This joint APAGE-APSDE Practice
Guideline is intended to be an educational tool that assists clinicians in
improving care for patients on antithrombotics who require emergency or elective
GI endoscopy in the Asian Pacific region.
PMID- 29331950
TI - Construction of an evaluation index system for determining the academic impact of
military medical scholars.
AB - INTRODUCTION: Academic papers are an essential manner for describing new ideas
and consolidating existing concepts in the field of military medicine. The
academic impact of military medical publications reflects the extent and depth of
recognition, acceptance and utilisation of the concepts transmitted in these
publications. The aim of this research was to construct an evaluation index
system suitable for evaluating the academic influence of scholars in the field of
military medicine. METHODS: Using the Delphi consensus methodology, 30 experts
from the field of military medicine, military medical information and library and
information science were asked during three rounds of questioning to score the
feasibility and importance of indicators that could be used to determine academic
impact. An analytic hierarchy process method was used to calculate the relative
weighting of each indicator in determining the final level of academic impact.
RESULTS: Eight evaluation indicators were agreed on to potentially determine
academic impact. These comprised: 'Web of Science documents', 'Citation impact',
'h-index', 'Percentage of international collaborations', 'Percentage of the top
10% of the cited frequency', 'Category normalised citation impact', 'Percentage
of documents cited' and 'The number of F1000 Recommended papers'. CONCLUSIONS:
The evaluation index system determined from this study combines the advantages of
both qualitative and quantitative recognised evaluation indicators, which are
subsequently weighted according to their importance in the field of military
medicine. It is hoped that this framework will provide a manner in the future for
comparing the potential academic impact of military medical scholars.
PMID- 29331949
TI - Bibliometric analysis of military trauma publications: 2000-2016.
AB - INTRODUCTION: Bibliometric tools can be used to identify the authors, topics and
research institutions that have made the greatest impact in a field of medicine.
The aim of this research was to analyse military trauma publications over the
last 16 years of armed conflict in order to highlight the most important lessons
that have translated into civilian practice and military doctrine as well as
identify emerging areas of importance. METHODS: A systematic search of research
published between January 2000 and December 2016 was conducted using the Thompson
Reuters Web of Science database. Both primary evidence and review publications
were included. Results were categorised according to relevance and topic and the
30 most cited publications were reviewed in full. The h-index, impact factors,
citation counts and citation analysis were used to evaluate results. RESULTS: A
plateau in the number of annual publications on military trauma was found, as was
a shift away from publications on wound and mortality epidemiology to
publications on traumatic brain injury (TBI), neurosurgery or blast injury to the
head. Extensive collaboration networks exist between highly contributing authors
and institutions, but less collaboration between authors from different
countries. The USA produced the majority of recent publications, followed by the
UK, Germany and Israel. CONCLUSIONS: In recent years, the number of publications
on TBI, neurosurgery or blast injury to the head has increased. It is likely that
the lessons of recent conflicts will continue to influence civilian medical
practice, particularly regarding the long-term effects of blast-related TBI.
PMID- 29331951
TI - SITA-Standard perimetry has better performance than FDT2 matrix perimetry for
detecting glaucomatous progression.
AB - PURPOSE: The Humphrey Matrix (FDT2) may be more sensitive in detecting
glaucomatous visual field loss than SITA standard automated perimetry (SAP)
performed on the Humphrey Field Analyzer (HFA). Therefore, FDT may be a good
candidate to determine disease progression in patients with glaucoma. Our aim was
to test the hypothesis that automated perimetry using the FDT2 would be equal to,
or more effective than, HFA SITA-Standard, in identifying glaucomatous
progression. METHODS: One hundred and twenty patients with glaucoma were tested
twice at baseline and every 6 months for 4 years with HFA SITA-Standard and FDT2.
FDT2 values were standardised to HFA SAP values. We used pointwise linear
regression (PLR) over the full data series to identify glaucomatous progression
and generated an array of results using three different criteria: (1) three or
more clustered test locations progressing, (2) three or more non-clustered test
locations progressing and (3) total number of progressing test locations. We
compared HFA SAP and FDT2 for the number of locations signalled by the PLR
detection algorithm. RESULTS: Regardless of the criteria, HFA SAP with SITA
Standard testing detected visual field progression at a higher rate than the FDT2
overall (P<0.001). CONCLUSION: HFA SAP identifies glaucomatous visual field
progression at a rate at least as high if not higher than FDT2.
PMID- 29331952
TI - Inter-relationship between ocular perfusion pressure, blood pressure, intraocular
pressure profiles and primary open-angle glaucoma: the Singapore Epidemiology of
Eye Diseases study.
AB - OBJECTIVE: To elucidate the inter-relationship between ocular perfusion pressure
(OPP), blood pressure (BP), intraocular pressure (IOP) profiles and primary open
angle glaucoma (POAG) in a multiethnic Asian population. METHODS: Participants
were recruited from the Singapore Epidemiology of Eye Diseases Study and
underwent standardised ocular and systemic examinations. POAG was defined
according to the International Society for Geographical and Epidemiological
Ophthalmology criteria. Logistic regression analyses with generalised estimating
equation models were performed and used to account for correlation between eyes.
RESULTS: A total of 9877 participants (19 587 eyes), including 213 POAG cases
(293 eyes) were included. Eyes with lowest quartile levels of systolic OPP (SOPP
<110 mm Hg) were 1.85 times (95% CI 1.16 to 2.95) likely to have POAG, compared
with eyes with mid-range SOPP levels (123-137 mm Hg; third quartile), after
adjusting for relevant covariates and IOP. Consistently, we found that lowest
quartile of systolic BP (SBP <124 mm Hg) was 1.69 times (95% CI 1.08 to 2.66)
likely to have POAG, compared with mid-range SBP levels (138-153 mm Hg; third
quartile). Furthermore, the effect of lower SBP on POAG was more pronounced in
eyes with IOP >=21 mm Hg (OR 3.90; 95% CI 1.24 to 12.30). Both the mean and
diastolic profiles of OPP and BP were not significantly associated with POAG,
after adjusting for relevant covariates and IOP. CONCLUSIONS: In this population
based sample of nearly 10 000 Asian individuals, we showed that low SOPP was
associated with POAG. This association was potentially in part secondary to low
SBP and high IOP. Our findings provide further clarity on the roles of OPP
surrogates and BP profiles in POAG.
PMID- 29331953
TI - Efficacy, tolerability and acceptability of oxycodone for cancer-related pain in
adults: an updated Cochrane systematic review.
AB - OBJECTIVES: To assess the efficacy, tolerability and acceptability of oxycodone
for cancer pain in adults METHODS: We searched CENTRAL, MEDLINE, MEDLINE In
Process, Embase, SCI, Conference Proceedings Citation Index-Science, BIOSIS,
PsycINFO and four trials registries to November 2016. RESULTS: We included 23
randomised controlled trials with 2144 patients analysed for efficacy and 2363
for safety. Meta-analyses showed no significant differences between controlled
release (CR) and immediate-release oxycodone in pain intensity or adverse events
but did show significantly better pain relief after treatment with CR morphine
compared with CR oxycodone. However, sensitivity analysis did not corroborate
this result. Meta-analyses of the adverse events showed a significantly lower
risk of hallucinations after treatment with CR oxycodone compared with CR
morphine, but no other differences. The remaining studies either compared
oxycodone in various formulations or compared oxycodone to different alternative
opioids. None found any clear superiority or inferiority of oxycodone in pain
relief or adverse events. The quality of this evidence base was limited by the
high/unclear risk of bias of the studies and the low event rates for many
outcomes. CONCLUSIONS: Oxycodone offers similar levels of pain relief and adverse
events to other strong opioids. However, hallucinations occurred less with CR
oxycodone than with CR morphine, but the quality of this evidence was very low,
so this finding should be treated with utmost caution. Our conclusions are
consistent with other reviews and suggest that oxycodone can be used first line
as an alternative to morphine. However, because it is cheaper, morphine generally
remains the first-line opioid of choice.
PMID- 29331954
TI - Dynamics of dignity and safety: a discussion.
PMID- 29331955
TI - Low-value care: an intractable global problem with no quick fix.
PMID- 29331957
TI - Mitral Valve Anatomic Predictors of Hemodynamic Success With Transcatheter Mitral
Valve Repair.
AB - BACKGROUND: Mitral regurgitation is a heterogeneous disease. Determining which
patients derive optimal outcomes from transcatheter edge-to-edge mitral valve
repair (TMVR) remains challenging. We sought to determine whether baseline mitral
valve anatomic characteristics are predictive of left atrial pressure (LAP)
changes during TMVR with MitraClip. METHODS AND RESULTS: Consecutive patients
with severe mitral regurgitation undergoing TMVR (n=112) underwent continuous
intraprocedural LAP monitoring and retrospective echocardiographic analysis for
specific mitral anatomic characteristics. Procedural success (optimal LAP
reduction) was defined as >=40% reduction in left atrial V-wave pressure compared
with baseline. Echocardiographic predictors of optimal LAP reduction and
increased postprocedure mean diastolic gradient were evaluated. Mean age was 79+/
14 years, and 36 patients (32%) were women. Primary, mixed, and secondary mitral
regurgitation were present in 78 patients (70%), 22 patients (20%), and 12
patients (10%), respectively. Baseline mean LAP and V-wave were 22+/-6 and 38+/
13 mm Hg; after TMVR, these decreased to 19+/-5 and 27+/-10 mm Hg, respectively
(P<0.0001 for both). Independent predictors of optimal LAP reduction were the
presence of a flail scallop, mitral regurgitation localized to a single scallop,
and high-quality 3-dimensional echocardiographic imaging. Independent predictors
of elevated postprocedure mean diastolic gradient were elevated preprocedure mean
diastolic gradient, mitral annular calcification, and implantation of multiple
clips. CONCLUSIONS: Mitral valve pathoanatomic features, including a flail
leaflet and single jet, are predictive of optimal LAP reduction with TMVR. High
quality 3-dimensional imaging may help select patients with the highest
likelihood of optimal hemodynamic results with TMVR. These data expand current
knowledge about patient selection for TMVR and deserve further study in larger
cohorts.
PMID- 29331956
TI - Adenosine Production by Biomaterial-Supported Mesenchymal Stromal Cells Reduces
the Innate Inflammatory Response in Myocardial Ischemia/Reperfusion Injury.
AB - BACKGROUND: During myocardial ischemia/reperfusion (MI/R) injury, there is
extensive release of immunogenic metabolites that activate cells of the innate
immune system. These include ATP and AMP, which upregulate chemotaxis, migration,
and effector function of early infiltrating inflammatory cells. These cells
subsequently drive further tissue devitalization. Mesenchymal stromal cells
(MSCs) are a potential treatment modality for MI/R because of their powerful anti
inflammatory capabilities; however, the manner in which they regulate the acute
inflammatory milieu requires further elucidation. CD73, an ecto-5'-nucleotidase,
may be critical in regulating inflammation by converting pro-inflammatory AMP to
anti-inflammatory adenosine. We hypothesized that MSC-mediated conversion of AMP
into adenosine reduces inflammation in early MI/R, favoring a micro-environment
that attenuates excessive innate immune cell activation and facilitates earlier
cardiac recovery. METHODS AND RESULTS: Adult rats were subjected to 30 minutes of
MI/R injury. MSCs were encapsulated within a hydrogel vehicle and implanted onto
the myocardium. A subset of MSCs were pretreated with the CD73 inhibitor,
alpha,beta-methylene adenosine diphosphate, before implantation. Using liquid
chromatography/mass spectrometry, we found that MSCs increase myocardial
adenosine availability following injury via CD73 activity. MSCs also reduce
innate immune cell infiltration as measured by flow cytometry, and hydrogen
peroxide formation as measured by Amplex Red assay. These effects were dependent
on MSC-mediated CD73 activity. Finally, through echocardiography we found that
CD73 activity on MSCs was critical to optimal protection of cardiac function
following MI/R injury. CONCLUSIONS: MSC-mediated conversion of AMP to adenosine
by CD73 exerts a powerful anti-inflammatory effect critical for cardiac recovery
following MI/R injury.
PMID- 29331958
TI - Platelet Secretion Defects and Acquired von Willebrand Syndrome in Patients With
Ventricular Assist Devices.
AB - BACKGROUND: The number of implanted ventricular assist devices (VADs) has
increased significantly recently. Bleeding, the most frequent complication,
cannot be solely attributed to anticoagulation therapy. Acquired von Willebrand
syndrome (AVWS) caused by increased shear stress is frequent in VAD patients and
can increase the bleeding risk. The HeartMate III (HM III) is a novel left VAD
featuring potential improvements over the HeartMate II. METHODS AND RESULTS: In
this study, we investigated the prevalence and onset of AVWS in 198 VAD patients.
To our knowledge, this is the largest cohort of VAD patients whose longitudinal
data on AVWS have been collected. We also analyzed whether AVWS is less severe in
HM III patients than in HeartMate II patients. Because platelet dysfunction can
raise the bleeding risk, we investigated platelet function in a subset of
patients. In total, 198 VAD patients and 60 patients with heart transplants as
controls were included in this study. The ratio of von Willebrand factor collagen
binding capacity to von Willebrand factor:antigen, multimer analyses, and
platelet function (especially secretion of alpha- and delta-granules) were
investigated. All 198 VAD patients developed AVWS. As soon as the VAD was
explanted, the AVWS disappeared within hours. AVWS was less severe in the HM III
patients than in the HeartMate II patients. The HM III patients had fewer
bleeding symptoms. In addition, VAD patients exhibited a platelet alpha- and
delta-granule secretion defect. CONCLUSIONS: AVWS develops in VAD patients and
may increase the bleeding risk. The HM III device causes less severe AVWS.
Platelet secretion defects should be investigated in VAD patients because they
also raise the bleeding risk. CLINICAL TRIAL REGISTRATION:
https://www.drks.de/drks_web. Unique identifier: DRKS00000649.
PMID- 29331959
TI - Probenecid Improves Cardiac Function in Patients With Heart Failure With Reduced
Ejection Fraction In Vivo and Cardiomyocyte Calcium Sensitivity In Vitro.
AB - BACKGROUND: Transient receptor potential vanilloid 2 is a calcium channel
activated by probenecid. Probenecid is a Food and Drug Administration-approved
uricosuric drug that has recently been shown to induce positive lusitropic and
inotropic effects in animal models through cardiomyocyte transient receptor
potential vanilloid 2 activation. The aim of this study was to test the
hypothesis that oral probenecid can improve cardiac function and symptomatology
in patients with heart failure with reduced ejection fraction and to further
elucidate its calcium-dependent effects on myocyte contractility. METHODS AND
RESULTS: The clinical trial recruited stable outpatients with heart failure with
reduced ejection fraction randomized in a single-center, double-blind, crossover
design. Clinical data were collected including a dyspnea assessment, physical
examination, ECG, echocardiogram to assess systolic and diastolic function, a 6
minute walk test, and laboratory studies. In vitro force generation studies were
performed on cardiomyocytes isolated from murine tissue exposed to probenecid or
control treatments. The clinical trial recruited 20 subjects (mean age 57 years,
mean baseline fractional shortening of 13.6+/-1.0%). Probenecid therapy increased
fractional shortening by 2.1+/-1.0% compared with placebo -1.7+/-1.0% (P=0.007).
Additionally, probenecid improved diastolic function compared with placebo by
decreasing the E/E' by -2.95+/-1.21 versus 1.32+/-1.21 in comparison to placebo
(P=0.03). In vitro probenecid increased myofilament force generation (92.36
versus 80.82 mN/mm2, P<0.05) and calcium sensitivity (pCa 5.67 versus 5.60,
P<0.01) compared with control. CONCLUSIONS: Probenecid improves cardiac function
with minimal effects on symptomatology and no significant adverse effects after 1
week in patients with heart failure with reduced ejection fraction and increases
force development and calcium sensitivity at the cardiomyocyte level. CLINICAL
TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier:
NCT01814319.
PMID- 29331960
TI - Pregnancy Loss and Carotid Intima-Media Thickness in Mexican Women.
AB - BACKGROUND: Cardiovascular disease in women often develops without conventional
risk factors. Prenatal loss is a common pregnancy outcome that may result in
physiological changes can increase the potential future risk of cardiovascular
disease. Insufficient information exists regarding the impact of pregnancy loss
on early markers of cardiovascular disease risk. METHODS AND RESULTS: Cross
sectional analysis of 1767 disease-free women from the MTC (Mexican Teachers'
Cohort) who had been pregnant was used to evaluate the relationship between
pregnancy loss and carotid intima-media thickness (IMT). Participants responded
to a questionnaire regarding their reproductive history, risk factors, and
medical conditions. We defined pregnancy loss as history of miscarriage and/or
stillbirth. Trained neurologists measured IMT using ultrasound. We log
transformed IMT and defined subclinical carotid atherosclerosis (SCA) as IMT
>=0.8 mm and/or plaque. We used multivariable linear and logistic regression
models to assess the relation of pregnancy loss, IMT, and SCA. The mean age of
participants was 49.8+/-5.1 years. The prevalence of pregnancy loss was 22%, and
we observed SCA in 23% of participants. Comparing participants who reported a
pregnancy loss and those who did not, the multivariable-adjusted odds ratio for
SCA was 1.52 (95% confidence interval, 1.12-2.06). Women who experienced a
stillbirth had 2.32 higher odds (95% confidence interval, 1.03-5.21) of SCA than
those who did not. Mean IMT appeared to be higher in women who reported a
pregnancy loss relative to those who did not; nevertheless, this was not
statistically significant. CONCLUSIONS: Pregnancy loss could be linked to
cardiovascular disease later in life. The key findings of our study await
confirmation and further investigation of the potential underlying mechanisms for
this association is required.
PMID- 29331961
TI - Combining Intravenous Thrombolysis and Antithrombotic Agents in Stroke: An
Update.
PMID- 29331963
TI - Response to: 'Standard dose of ustekinumab for childhood-onset deficiency of
interleukin-36 receptor antagonist' by Cherqaoui et al.
PMID- 29331962
TI - Splicing variant of WDFY4 augments MDA5 signalling and the risk of clinically
amyopathic dermatomyositis.
AB - OBJECTIVES: Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group
of rare autoimmune diseases in which both genetic and environmental factors play
important roles. To identify genetic factors of IIM including polymyositis,
dermatomyositis (DM) and clinically amyopathic DM (CADM), we performed the first
genome-wide association study for IIM in an Asian population. METHODS: We
genotyped and tested 496 819 single nucleotide polymorphism for association using
576 patients with IIM and 6270 control subjects. We also examined the causal
mechanism of disease-associated variants by in silico analyses using publicly
available data sets as well as by in in vitro analyses using reporter assays and
apoptosis assays. RESULTS: We identified a variant in WDFY4 that was
significantly associated with CADM (rs7919656; OR=3.87; P=1.5*10-8). This variant
had a cis-splicing quantitative trait locus (QTL) effect for a truncated
WDFY4isoform (tr-WDFY4), with higher expression in the risk allele.
Transexpression QTL analysis of this variant showed a positive correlation with
the expression of NF-kappaB associated genes. Furthermore, we demonstrated that
both WDFY4 and tr-WDFY4 interacted with pattern recognition receptors such as
TLR3, TLR4, TLR9 and MDA5 and augmented the NF-kappaB activation by these
receptors. WDFY4 isoforms also enhanced MDA5-induced apoptosis to a greater
extent in the tr-WDFY4-transfected cells. CONCLUSIONS: As CADM is characterised
by the appearance of anti-MDA5 autoantibodies and severe lung inflammation, the
WDFY4 variant may play a critical role in the pathogenesis of CADM.
PMID- 29331964
TI - What are the characteristics of vitamin D metabolism in opioid dependence? An
exploratory longitudinal study in Australian primary care.
AB - OBJECTIVE: Compare vitamin D levels in opioid dependence and control population
and adjust for relevant confounding effects. Nuclear hormone receptors (including
the vitamin D receptor) have been shown to be key transducers and regulators of
intracellular metabolism and comprise an important site of pathophysiological
immune and metabolic dysregulation potentially contributing towards pro-ageing
changes observed in opioid-dependent patients (ODPs). DESIGN: Longitudinal
prospective comparing ODPs with general medical controls (GMCs). SETTING: Primary
care. PARTICIPANTS: Prospective review comparing 1168 ODP (72.5% men) and 415 GMC
(51.6% men, p<0.0001). Mean ages were 33.92+/-0.31 (mean+/-SEM) and 41.22+/-1.32
years, respectively (p<0.0001). Opioid use in the ODP has been previously
reported and shown to be typical. INTERVENTIONS: Nil. Observational study only.
PRIMARY AND SECONDARY OUTCOMES: Serum vitamin D levels and relevant biochemical
parameters. RESULTS: Vitamin D levels were higher in the ODP (70.35+/-1.16 and
57.06+/-1.81 nmol/L, p<0.0001). The difference in ages between the two groups was
handled in an age-matched case-control subanalysis and also by multiple
regression. Sexes were analysed separately. The age:status (or age:time:status)
was significant in case-control, cross-sectional and longitudinal analyses in
both sexes (p<0.05). Modelled vitamin D was 62.71 vs 57.81 nmol/L in the two
groups. Time-dependent mixed-effects models quadratic in age outperformed linear
only models (p=0.0377). ODP vitamin D was shown to vary with age and to correlate
with alanine aminotransferase establishing it as a biomarker of age in this
group. Hepatitis C seronegativity was significant in regression models (from
p=0.0015). CONCLUSION: Vitamin D was higher in ODP in both sexes in bivariate,
cross-sectional, case-control and longitudinal analyses and was robust to the
inclusion of metabolic and immune biomarkers. That Hepatitis C seronegativity was
significant suggests opioid dependence has an effect beyond simply that of its
associated hepatitides. This finding may relate to the accelerated ageing process
previously described in opioid dependence.
PMID- 29331965
TI - Right Iliac Fossa Pain Treatment (RIFT) Study: protocol for an international,
multicentre, prospective observational study.
AB - INTRODUCTION: Patients presenting with right iliac fossa (RIF) pain are a common
challenge for acute general surgical services. Given the range of potential
pathologies, RIF pain creates diagnostic uncertainty and there is subsequent
variation in investigation and management. Appendicitis is a diagnosis which must
be considered in all patients with RIF pain; however, over a fifth of patients
undergoing appendicectomy, in the UK, have been proven to have a histologically
normal appendix (negative appendicectomy). The primary aim of this study is to
determine the contemporary negative appendicectomy rate. The study's secondary
aims are to determine the rate of laparoscopy for appendicitis and to validate
the Appendicitis Inflammatory Response (AIR) and Alvarado prediction scores.
METHODS AND ANALYSIS: This multicentre, international prospective observational
study will include all patients referred to surgical specialists with either RIF
pain or suspected appendicitis. Consecutive patients presenting within 2-week
long data collection periods will be included. Centres will be invited to
participate in up to four data collection periods between February and August
2017. Data will be captured using a secure online data management system. A
centre survey will profile local policy and service delivery for management of
RIF pain. ETHICS AND DISSEMINATION: Research ethics are not required for this
study in the UK, as determined using the National Research Ethics Service
decision tool. This study will be registered as a clinical audit in participating
UK centres. National leads in countries outside the UK will oversee appropriate
registration and study approval, which may include completing full ethical
review. The study will be disseminated by trainee-led research collaboratives and
through social media. Peer-reviewed publications will be published under
corporate authorship including 'RIFT Study Group' and 'West Midlands Research
Collaborative'.
PMID- 29331966
TI - Effectiveness and safety of oral sedation in adult patients undergoing dental
procedures: protocol for a systematic review.
AB - INTRODUCTION: The management of anxious patients undergoing dental procedures is
still a challenge in clinical practice. Despite a wide variety of drugs for oral
sedation in adult patients, there are relatively few systematic reviews that
compare the effectiveness and safety of different drugs administered via this
route. Thus, this study will evaluate the effectiveness and safety of oral
sedation with benzodiazepines and other agents to patients undergoing dental
surgical procedures. METHOD/DESIGN: We will conduct a systematic review and, if
appropriate, a meta-analysis of randomised controlled clinical trials that will
evaluate the use of conscious sedation administered orally to adult patients
undergoing oral surgery. The search will be conducted using electronic databases,
such as the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE
(via Ovid), EMBASE (via Ovid), CINAHL (via Ovid), Lilacs (SciELO) and Capes
database, without restriction of languages or date of publication. Primary
outcomes include anxiety, sedation, treatment satisfaction, pain and adverse
effects. Secondary outcomes include vital parameters (heart rate, respiratory
rate and blood pressure) and patient cooperation during intervention. A team of
reviewers will independently assess each citation for eligibility and in
duplicates. For eligible studies, the same reviewers will perform data
extraction, risk of bias assessment and determination of the overall quality of
evidence using the Grading of Recommendations Assessment, Development and
Evaluation classification system. ETHICS AND DISSEMINATION: The evidence gathered
from this study should provide dental surgeons with knowledge on the
effectiveness and safety of oral sedation in adults requiring dental surgical
procedures. This in turn should contribute towards the decision-making process in
dental practice, minimising the risks of anxiety and ineffective pain control in
clinical procedures, as well as possible side effects. Ethics approval is not
required in protocols for systematic reviews. The systematic review will be
published in a peer-reviewed journal and presented at conferences. PROSPERO
REGISTRATION NUMBER: CRD42017057142.
PMID- 29331967
TI - Understanding frailty: a qualitative study of European healthcare policy-makers'
approaches to frailty screening and management.
AB - OBJECTIVE: To elicit European healthcare policy-makers' views, understanding and
attitudes about the implementation of frailty screening and management strategies
and responses to stakeholders' views. DESIGN: Thematic analysis of semistructured
qualitative interviews. SETTING: European healthcare policy departments.
PARTICIPANTS: Seven European healthcare policy-makers representing the European
Union (n=2), UK (n=2), Italy (n=1), Spain (n=1) and Poland (n=1). Participants
were sourced through professional networks and the European Commission
Authentication Service website and were required to be in an active healthcare
policy or decision-making role. RESULTS: Seven themes were identified. Our
findings reveal a 'knowledge gap', around frailty and awareness of the
malleability of frailty, which has resulted in restricted ownership of frailty by
specialists. Policy-makers emphasised the need to recognise frailty as a clinical
syndrome but stressed that it should be managed via an integrated and
interdisciplinary response to chronicity and ageing. That is, through social co
production. This would require a culture shift in care with redeployment of
existing resources to deliver frailty management and intervention services.
Policy-makers proposed barriers to a culture shift, indicating a need to be
innovative with solutions to empower older adults to optimise their health and
well-being, while still fully engaging in the social environment. The cultural
acceptance of an integrated care system theme described the complexities of
institutional change management, as well as cultural issues relating to working
democratically, while in signposting adult care, the need for a personal
navigator to help older adults to access appropriate services was proposed.
Policy-makers also believed that screening for frailty could be an effective tool
for frailty management. CONCLUSIONS: There is potential for frailty to be managed
in a more integrated and person-centred manner, overcoming the challenges
associated with niche ownership within the healthcare system. There is also a
need to raise its profile and develop a common understanding of its malleability
among stakeholders, as well as consistency in how and when it is measured.
PMID- 29331969
TI - Temporal trends in antithrombotic treatment of real-world UK patients with newly
diagnosed atrial fibrillation: findings from the GARFIELD-AF registry.
AB - OBJECTIVE: To investigate evolving patterns in antithrombotic treatment in UK
patients with newly diagnosed non-valvular atrial fibrillation (AF). DESIGN:
Prospective, multicentre, international registry. SETTING: 186 primary care
practices in the UK. PARTICIPANTS: 3482 participants prospectively enrolled in
four sequential cohorts (cohort 2 (C2) n=830, diagnosed September 2011 to April
2013; cohort 3 (C3) n=902, diagnosed April 2013 to June 2014; cohort 4 (C4)
n=850, diagnosed July 2014 to June 2015; cohort 5 (C5) n=900, diagnosed June 2015
to July 2016). Participants had newly diagnosed non-valvular AF and at least one
risk factor for stroke, were aged >=18, and provided informed consent. MAIN
OUTCOME MEASURES: Antithrombotic treatment initiated at diagnosis, overall and
according to stroke and bleeding risks. Stroke risk was retrospectively
calculated using CHA2DS2-VASc (cardiac failure, hypertension, age >=75 (doubled),
diabetes, stroke (doubled)-vascular disease, age 65-74 and sex category (female))
and bleeding risk using HAS-BLED (hypertension, abnormal renal/liver function (1
point each), stroke, bleeding history or predisposition, elderly (>65),
drugs/alcohol concomitantly (1 point each)). RESULTS: 42.7% were women and the
mean age was 74.5 years. The median CHA2DS2-VASc score was 3 in all cohorts and
the median HAS-BLED score was 2 in all cohorts. There was a statistically
significant increase in the use of anticoagulant therapy from C2 to C5 (C2 54.7%,
C3 60.3%, C4 73.1%, C5 73.9%; P value for trend <0.0001). The increase in the use
of anticoagulant was mainly in patients with CHA2DS2-VASc >=2. The use of vitamin
K antagonists (VKAs)+/-antiplatelet (AP) drugs decreased from C2 to C5 (C2 53.3%,
C3 52.1%, C4 50.3%, C5 30.6%), while the use of non-vitamin K antagonist oral
anticoagulants (NOACs)+/-AP increased (C2 1.3%, C3 8.0%, C4 22.7%, C5 43.3%). The
use of AP only decreased (C2 36.4%, C3 25.5%, C4 11.9%, C5 10.5%), as did the
combination therapy of VKA+AP (C2 13.6%, C3 11.0%, C4 9.6%, C5 5.8%). CONCLUSION:
There has been a progressive increase in the proportion of patients newly
diagnosed with AF receiving guideline-recommended therapy in the UK, potentially
driven by the availability of NOACs. TRIAL REGISTRATION NUMBER: NCT01090362; Pre
results.
PMID- 29331968
TI - Association between health service utilisation of internal migrant children and
parents' acculturation in Guangdong, China: a cross-sectional study.
AB - OBJECTIVES: To assess the health service utilisation of internal migrant children
in Guangdong, China, and to explore the association between children's health
service utilisation and their parents' acculturation. DESIGN: Cross-sectional
survey between April and May 2016. SETTING: Six society-run schools of Tianhe and
Baiyun districts in Guangzhou City of China. PARTICIPANTS: We recruited all
students at grade 7 or 8 and one of their parents who resided in Guangzhou over 6
months without permanent registered residence (hukou) in Guangzhou (1161 pairs
completed this survey). 258 children were ill within the past 2 weeks or during
the last year. MAIN OUTCOME MEASURES: The main outcome was self-reported health
service utilisation. Logistic regression analysis was conducted to explore the
association between children's unmet needs for outpatient or inpatient service
and their parents' acculturation (categorised into high, middle and low groups).
RESULTS: In total, 216 children, or 18.6% of the total subjects, were ill within
the past 2 weeks and were in need of outpatient service; 94 children, or 8.1% of
the total subjects, were in need of inpatient service. Among them, 17.6% and
46.8% of the migrant children had unmet needs for outpatient and inpatient
services, respectively. After controlling for enabling resources and predisposing
characteristics, migrant children with parents in the middle-acculturation group
(adjusted OR=3.17, 95% CIs 1.2 to 8.3, P<0.05) were more likely to have an unmet
outpatient need than high-acculturation or low-acculturation groups, although
only statistically significant when comparing with the high-acculturation group.
Stratified analysis suggested that this association could be moderated by their
family economic status. CONCLUSIONS: Our study suggested that the association
between migrant children's health service utilisation and their parents'
acculturation was complex and could be moderated by family economic status.
Increasing the service utilisation among migrant children requires improving the
acculturation and economic status of the parents of internal migrants.
PMID- 29331970
TI - Is there a social gradient of sarcopenia? A meta-analysis and systematic review
protocol.
AB - INTRODUCTION: Sarcopenia (or loss of muscle mass and function) is a relatively
new area within the field of musculoskeletal research and medicine. Investigating
whether there is a social gradient, including occupation type and income level,
of sarcopenia, as observed for other diseases, will contribute significantly to
the limited evidence base for this disease. This new information may inform the
prevention and management of sarcopenia and widen the evidence base to support
existing and future health campaigns. METHODS AND ANALYSIS: We will conduct a
systematic search of the databases PubMed, Ovid, CINAHL, Scopus and EMBASE to
identify articles that investigate associations between social determinants of
health and sarcopenia in adults aged 50 years and older. Eligibility of the
selected studies will be determined by two independent reviewers. The
methodological quality of eligible studies will be assessed according to
predetermined criteria. Established statistical methods to identify and control
for heterogeneity will be used, and where appropriate, we will conduct a meta
analysis. In the event that heterogeneity prevents numerical synthesis, a best
evidence analysis will be employed. This systematic review protocol adheres to
the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols
reporting guidelines and will be registered with the International Prospective
Register of Systematic Reviews (PROSPERO). ETHICS AND DISSEMINATION: This
systematic review will use published data, thus ethical permissions will not be
required. In addition to peer-reviewed publication, our results will be presented
at (inter)national conferences relevant to the field of sarcopenia, ageing and/or
musculoskeletal health and disseminated both electronically and in print.
PROSPERO REGISTRATION NUMBER: CRD42017072253.
PMID- 29331971
TI - A study protocol for a non-randomised comparison trial evaluating the feasibility
and effectiveness of a mobile cognitive-behavioural programme with integrated
coaching for anxious adults in primary care.
AB - INTRODUCTION: Generalised anxiety disorder (GAD) and subclinical GAD are highly
prevalent in primary care. Unmanaged anxiety worsens quality of life in patients
seen in primary care practices and leads to increased medical utilisation and
costs. Programmes that teach patients cognitive-behavioural therapy (CBT)
techniques have been shown to improve anxiety and to prevent the evolution of
anxiety symptoms to disorders, but access and engagement have hampered
integration of CBT into medical settings. METHODS AND ANALYSIS: This pragmatic
study takes place in University of Pittsburgh Medical Center primary care
practices to evaluate a coach-supported mobile cognitive- behavioural programme
(Lantern) on anxiety symptoms and quality of life. Clinics were non-randomly
assigned to either enhanced treatment as usual or Lantern. All clinics provide
electronic screening for anxiety and, within clinics assigned to Lantern,
patients meeting a threshold level of mild anxiety (ie, >5 on Generalised Anxiety
Disorder 7-Item Questionnaire (GAD-7)) are referred to Lantern. The first study
phase is aimed at establishing feasibility, acceptability and effectiveness. The
second phase focuses on long-term impact on psychosocial outcomes, healthcare
utilisation and clinic/provider adoption/sustainable implementation using a
propensity score matched parallel group study design. Primary outcomes are
changes in anxiety symptoms (GAD-7) and quality of life (Short-Form Health
Survey) between baseline and 6-month follow-ups, comparing control and
intervention. Secondary outcomes include provider and patient satisfaction,
patient engagement, durability of changes in anxiety symptoms and quality of life
over 12 months and the impact of Lantern on healthcare utilisation over 12
months. Patients from control sites will be matched to the patients who use the
mobile app. ETHICS AND DISSEMINATION: Ethics and human subject research approval
were obtained. A data safety monitoring board is overseeing trial data and
ethics. Results will be communicated to participating primary care practices,
published and presented at clinical and scientific conferences. TRIAL
REGISTRATION NUMBER: NCT03035019.
PMID- 29331972
TI - Cohort profile: the Comparative Outcomes And Service Utilization Trends (COAST)
Study among people living with and without HIV in British Columbia, Canada.
AB - PURPOSE: The Comparative Outcomes And Service Utilization Trends (COAST) Study in
British Columbia (BC), Canada, was designed to evaluate the determinants of
health outcomes and health care services use among people living with HIV (PLHIV)
as they age in the period following the introduction of combination
antiretroviral therapy (cART). The study also assesses how age-associated
comorbidities and health care use among PLHIV may differ from those observed in
the general population. PARTICIPANTS: COAST was established through a data
linkage between two provincial data sources: The BC Centre for Excellence in
HIV/AIDS Drug Treatment Program, which centrally manages cART dispensation across
BC and contains prospectively collected data on demographic, immunological,
virological, cART use and other clinical information for all known PLHIV in BC;
and Population Data BC, a provincial data repository that holds individual event
level, longitudinal data for all 4.6 million BC residents. COAST participants
include 13 907 HIV-positive adults (>=19 years of age) and a 10% random sample
inclusive of 516 340 adults from the general population followed from 1996 to
2013. FINDINGS TO DATE: For all participants, linked individual-level data
include information on demographics, health service use (eg, inpatient care,
outpatient care and prescription medication dispensations), mortality, and HIV
diagnostic and clinical data. Publications from COAST have demonstrated the
significant mortality reductions and dramatic changes in the causes of death
among PLHIV from 1996 to 2012, differences in the amount of time spent in a
healthy state by HIV status, and high levels of injury and mood disorder
diagnosis among PLHIV compared with the general population. FUTURE PLANS: To
capture the dynamic nature of population health parameters, regular data updates
and a refresh of the data linkage are planned to occur every 2 years, providing
the basis for planned analysis to examine age-associated comorbidities and
patterns of health service use over time.
PMID- 29331973
TI - Family-focused practices in addictions: a scoping review protocol.
AB - INTRODUCTION: Families are significantly impacted by addictions and family
involvement in treatment can reduce the harms and can also improve treatment
entry, treatment completion and treatment outcomes for the individual coping with
an addiction. Although the benefits of family-focused practices in addictions
have been documented, services continue to have an individual focus and research
on this topic is also limited. The objective of this study is to map the extent,
range and nature of evidence available examining family interventions in
addictions and identify gaps to guide future research, policy and practice.
METHODS AND ANALYSIS: This is a scoping review using the five-stage framework
developed by Arksey and O'Malley. We will include published and unpublished
empirical studies focusing on any type of family interventions in addiction
treatment between 2000 and the present in English or French. A reviewer will
search for literature that meets the inclusion criteria through the following
electronic databases: MEDLINE, PsycINFO and Social Services Abstracts. For a
comprehensive search, we will also hand-search reference lists, web sites and key
journals. Data will be charted and sorted using a thematic analysis approach.
ETHICS AND DISSEMINATION: This review will be the first to examine all forms of
family-focused practices for both substance use and problem gambling treatment
for adults. It will provide information about existing service provisions and
gaps in practice. This review can be used to start moving towards the development
of best practices for families in addiction treatment. The results will be
disseminated through a peer-reviewed journal and at mental health and addiction
conferences.
PMID- 29331974
TI - What are the physical and psychological health effects of suicide bereavement on
family members? An observational and interview mixed-methods study in Ireland.
AB - OBJECTIVES: Research focussing on the impact of suicide bereavement on family
members' physical and psychological health is scarce. The aim of this study was
to examine how family members have been physically and psychologically affected
following suicide bereavement. A secondary objective of the study was to describe
the needs of family members bereaved by suicide. DESIGN: A mixed-methods study
was conducted, using qualitative semistructured interviews and additional
quantitative self-report measures of depression, anxiety and stress (DASS-21).
SETTING: Consecutive suicide cases and next-of-kin were identified by examining
coroner's records in Cork City and County, Ireland from October 2014 to May 2016.
PARTICIPANTS: Eighteen family members bereaved by suicide took part in a
qualitative interview. They were recruited from the Suicide Support and
Information System: A Case-Control Study (SSIS-ACE), where family members
bereaved by suicide (n=33) completed structured measures of their well-being.
RESULTS: Qualitative findings indicated three superordinate themes in relation to
experiences following suicide bereavement: (1) co-occurrence of grief and health
reactions; (2) disparity in supports after suicide and (3) reconstructing life
after deceased's suicide. Initial feelings of guilt, blame, shame and anger often
manifested in enduring physical, psychological and psychosomatic difficulties.
Support needs were diverse and were often related to the availability or absence
of informal support by family or friends. Quantitative results indicated that the
proportion of respondents above the DASS-21 cut-offs respectively were 24% for
depression, 18% for anxiety and 27% for stress. CONCLUSIONS: Healthcare
professionals' awareness of the adverse physical and psychosomatic health
difficulties experienced by family members bereaved by suicide is essential.
Proactively facilitating support for this group could help to reduce the negative
health sequelae. The effects of suicide bereavement are wide-ranging, including
high levels of stress, depression, anxiety and physical health difficulties.
PMID- 29331975
TI - Is postoperative bracing after pedicle screw fixation of spine fractures
necessary? Study protocol of the ORNOT study: a randomised controlled multicentre
trial.
AB - INTRODUCTION: The most common surgical treatment of traumatic spine fractures is
through a posterior approach using pedicle screws and rods. Postoperative
treatment protocols including the use of postoperative orthoses however differ
between hospitals and surgeons. A three-point hyperextension orthosis is designed
to support proper posture and unload the anterior column. Some motion remains
when wearing an orthosis, and its main value in postoperative treatment is
therefore believed to be pain relief and patient confidence. This could
consequently shorten recovery time. On the other hand, an orthosis could also
lead to muscle weakness and slow down recovery. Any orthosis-related
complications might also be avoided. Additionally, recent studies on conservative
fracture treatment show no difference in radiological outcomes with or without an
orthosis. To date, no randomised studies have been performed on the use of
postoperative orthoses. METHODS AND ANALYSIS: Patients undergoing posterior
fixation with pedicle screws for a traumatic thoracolumbar fracture (T7-L4) will
be included in this randomised controlled multicentre non-inferiority trial.
Forty-six patients will be randomised 1:1 to one of the two parallel groups; one
group will wear a postoperative orthosis for 6 weeks followed by 6 weeks of
weaning and one group will not wear an orthosis. The primary outcome is pain at 6
weeks reported on the Numerical Rating Scale. Secondary outcomes consist of pain
on other moments, analgesic use, complications and length of hospital stay,
quality of life (EuroQuol 5 Dimensions), back pain-related function (Oswestry
Disability Index) and radiological outcomes with a follow-up of 1 year. Orthosis
compliance is monitored weekly in the orthosis group. ETHICS AND DISSEMINATION:
The institutional review board (METc VUmc) approved this study on 11 October 2016
under case number 2016.389. After completion of the trial, the results will be
offered to an international scientific journal for peer-reviewed publication.
TRIAL REGISTRATION NUMBER: NCT03097081 and NTR6285; Pre-results.
PMID- 29331976
TI - Concealment of type 1 diabetes at work in Finland: a mixed-method study.
AB - OBJECTIVES: To explore the possible reasons for concealing type 1 diabetes (T1D)
at work. METHODS: The main set of data came from a cross-sectional survey
(response rate 49.3%), the participants of which were 688 wage earners with T1D.
Concealment of T1D was measured by asking respondents have they ever during their
working career hidden their diabetes from their (A) colleagues and (B) line
manager. Furthermore, semistructured interviews (n=20) were conducted to obtain
deeper understanding. Questionnaire data were analysed using logistic regression
analyses and qualitative interviews with inductive thematic analysis. RESULTS:
About 30% of wage earners with T1D had concealed their condition during their
working career from their colleagues and almost 20% from their line manager.
Individuals aged 18-44 years age were more likely to conceal their T1D from their
colleagues than older workers during their working career. Not disclosing T1D to
the extended family (OR 5.24 (95% CI 2.06 to 13.35)), feeling an outsider at work
(OR 2.47 (95% CI 1.58 to 3.84)), being embarrassed by receiving special attention
at work (OR 1.99 (95% CI 1.33 to 2.96)) and neglecting treatment at work (OR 1.59
(95% CI 1.01 to 2.48)) were all associated with concealment of T1D from
colleagues. The youngest age group of 18-24 years were more likely to conceal
their T1D from their line managers than the older age groups during their working
career. Not disclosing T1D to the extended family (OR 4.41 (95% CI 1.72 to
11.32)), feeling like an outsider at work (OR 2.51 (1.52 to 4.14)) and being
embarrassed by receiving special attention at work (OR 1.81 (95% CI 1.13 to
2.91)) were associated with concealment of T1D from line managers. From the
interviews, five main themes related to concealment emerged, expressing fears
related to the consequences of telling: (1) being perceived as weak, (2) job
discrimination, (3) unwanted attention, (4) being seen as a person who uses their
T1D for seeking advantages and (5) losing privacy. CONCLUSIONS: A considerable
proportion of wage earners with T1D are concealing their diagnosis often because
of feelings associated with stigma. Both overemphasis and underestimation of T1D
at work by the colleagues or line manager may lead to concealing T1D and may thus
be harmful to self-management of T1D. The obstacles in disclosing T1D might be
diminished by giving adequate information at the workplace about the condition
and its significance.
PMID- 29331977
TI - Clinical outcomes and prognostic factors in patients with spinal dural
arteriovenous fistulas : a prospective cohort study in two Chinese centres.
AB - BACKGROUND: The short-term outcomes and prognostic factors of patients with
spinal dural arteriovenous fistulas (SDAVFs) have not been defined in large
cohorts. OBJECTIVE: To define the short-term clinical outcomes and prognostic
factors in patients with SDAVFs. METHODS: A prospective cohort of 112 patients
with SDAVFs were included consecutively in this study. The patients were serially
evaluated with the modified Aminoff and Logue's Scale (mALS) one day before
surgery and at 3 months, 6 months and 12 months after treatment. Univariate and
multivariate analyses were performed to identify demographic, clinical and
procedural factors related to favourable outcome. RESULTS: A total of 94 patients
(mean age 53.5 years, 78 were men) met the criteria and are included in the final
analyses. Duration of symptom ranged from 0.5 to 66 months (average time period
of 12.7 months). The location of SDAVFs was as follows: 31.6% above T7 level,
48.4% between T7 and T12 level (including T7 and T12) and 20.0% below T12 level.
A total of 81 patients (86.2%) underwent neurosurgical treatment, 10 patients
(10.6%) underwent endovascular treatment, and 3 patients (3.2%) underwent
neurosurgical treatment after unsuccessful embolisation. A total of 78 patients
demonstrated an improvement in mALS score of one point or greater at 12 months.
Preoperative mALS score was associated with clinical improvement after adjusting
for age, gender, duration of symptoms, location of fistula and treatment modality
using unconditional logistic regression analysis (p<0.05). CONCLUSION:
Approximately four fifths of the patients experienced clinical improvement at 12
months and preoperative mALS was the strongest predictor of clinical improvement
in the cohort.
PMID- 29331978
TI - Postdischarge service utilisation and outcomes among Chinese and South Asian
psychiatric inpatients in Ontario, Canada: a population-based cohort study.
AB - OBJECTIVE: We sought to examine the short-term and long-term impacts of
psychiatric hospitalisations among patients of Chinese and South Asian origin.
DESIGN: Retrospective population-based cohort study using linked health
administrative data. SETTING: We examined all adult psychiatric inpatients
discharged between 1 April 2006 and 31 March 2014 in Ontario, Canada, who were
classified as Chinese, South Asian and all other ethnicities (ie, 'general
population') using a validated algorithm. We identified 2552 Chinese, 2439 South
Asian and 127 142 general population patients. PRIMARY AND SECONDARY OUTCOME
MEASURES: We examined psychiatric severity measures at admission and discharge
and performed multivariable logistic regression analyses to examine 30-day, 180
day and 365-day postdischarge service utilisation and outcomes, comparing each of
the ethnic groups with the reference population, after adjustment for age, sex,
income, education, marital status, immigration status, community size and
discharge diagnosis. RESULTS: Despite presenting to hospital with greater illness
severity, Asian psychiatric inpatients had shorter lengths of hospital stay and
greater absolute improvements in mental health and functional status at discharge
compared with other inpatients. After hospitalisation, Chinese patients were more
likely to visit psychiatrists and South Asian patients were more likely to seek
mental healthcare from general practitioners. They were also less likely to have
a psychiatric readmission or die 1 year following hospitalisation (adjusted
ORChinese=0.87; 95% CI 0.79 to 0.97; adjusted ORSouth Asian=0.82, 95% CI 0.73 to
0.91). Findings were consistent across genders, psychiatric diagnoses and
immigrant groups. CONCLUSION: Once hospitalised, patients of Chinese and South
Asian origin fared as well as or better than general population patients at
discharge and following discharge, and had a positive trajectory of psychiatric
service utilisation.
PMID- 29331979
TI - Now you see me: a pragmatic cohort study comparing first and final radiological
diagnoses in the emergency department.
AB - OBJECTIVES: To (1) compare timely but preliminary and definitive but delayed
radiological reports in a large urban level 1 trauma centre, (2) assess the
clinical significance of their differences and (3) identify clinical predictors
of such differences. DESIGN, SETTING AND PARTICIPANTS: We performed a
retrospective record review for all 2914 patients who presented to our university
affiliated emergency department (ED) during a 6-week period. In those that
underwent radiological imaging, we compared the patients' discharge letter from
the ED to the definitive radiological report. All identified discrepancies were
assessed regarding their clinical significance by trained raters, independent and
in duplicate. A binary logistic regression was performed to calculate the
likelihood of discrepancies based on readily available clinical data. RESULTS:
1522 patients had radiographic examinations performed. Rater agreement on the
clinical significance of identified discrepancies was substantial (kappa=0.86).
We found an overall discrepancy rate of 20.35% of which about one-third (7.48%
overall) are clinically relevant. A logistic regression identified patients' age,
the imaging modality and the anatomic region under investigation to be predictive
of future discrepancies. CONCLUSIONS: Discrepancies between radiological
diagnoses in the ED are frequent and readily available clinical factors predict
their likelihood. Emergency physicians should reconsider their discharge
diagnosis especially in older patients undergoing CT scans of more than one
anatomic region.
PMID- 29331980
TI - DMC1 mutation that causes human non-obstructive azoospermia and premature ovarian
insufficiency identified by whole-exome sequencing.
AB - BACKGROUND: The genetic causes of the majority of male and female infertility
caused by human non-obstructive azoospermia (NOA) and premature ovarian
insufficiency (POI) with meiotic arrest are unknown. OBJECTIVE: To identify the
genetic cause of NOA and POI in two affected members from a consanguineous
Chinese family. METHODS: We performed whole-exome sequencing of DNA from both
affected patients. The identified candidate causative gene was further verified
by Sanger sequencing for pedigree analysis in this family. In silico analysis was
performed to functionally characterise the mutation, and histological analysis
was performed using the biopsied testicle sample from the male patient with NOA.
RESULTS: We identified a novel homozygous missense mutation (NM_007068.3:
c.106G>A, p.Asp36Asn) in DMC1, which cosegregated with NOA and POI phenotypes in
this family. The identified missense mutation resulted in the substitution of a
conserved aspartic residue with asparaginate in the modified H3TH motif of DMC1.
This substitution results in protein misfolding. Histological analysis
demonstrated a lack of spermatozoa in the male patient's seminiferous tubules.
Immunohistochemistry using a testis biopsy sample from the male patient showed
that spermatogenesis was blocked at the zygotene stage during meiotic prophase I.
CONCLUSIONS: To the best of our knowledge, this is the first report identifying
DMC1 as the causative gene for human NOA and POI. Furthermore, our pedigree
analysis shows an autosomal recessive mode of inheritance for NOA and POI caused
by DMC1 in this family.
PMID- 29331981
TI - Variant in C-terminal region of intestinal alkaline phosphatase associated with
benign familial hyperphosphatasaemia.
AB - BACKGROUND: A genetic diagnosis has been rarely performed in benign familial
hyperphosphatasaemia, and molecular mechanism largely remains unclear.
OBJECTIVES: We encountered a case with benign familial hyperphosphatasaemia of
intestinal alkaline phosphatase (IAP). To elucidate the molecular mechanism, we
performed ALPI gene sequencing and in vitro protein expression analysis. METHODS:
ALPI gene was sequenced by long-range PCR and massively parallel sequencing. The
soluble and membrane-bound ALP activities of the cultured cell line, transfected
with the wild-type or variant-type ALPI gene were analysed by a
glycosylphosphatidylinositol (GPI)-cleaving assay. RESULTS: We identified a
deletion-insertion variant in the C-terminal end of the ALPI gene. This variant
causes the attenuation of the hydrophobicity in GPI-anchor signal of IAP. An in
vitro GPI-cleaving assay demonstrated that the membrane-bound IAP was greatly
decreased, whereas the soluble IAP was increased, in the variant IAP.
CONCLUSIONS: The C-terminal variant in ALPI causes the benign familial
hyperphosphatasaemia of IAP by the attenuation of the membrane-binding
capability.
PMID- 29331982
TI - A false-carrier state for the c.579G>A mutation in the NCF1 gene in Ashkenazi
Jews.
AB - BACKGROUND: Mutations in the NCF1 gene that encodes p47phox, a subunit of the
NADPH oxidase complex, cause chronic granulomatous disease (CGD). In Kavkazi
Jews, a c.579G>A (p.Trp193Ter) mutation in NCF1 is frequently found, leading to
CGD. The same mutation is found in about 1% of Ashkenazi Jews, although Ashkenazi
CGD patients with this mutation have never been described. METHODS: We used
Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), gene
scan analysis and Ion Torrent Next Generation Sequencing for genetic analysis,
and measured NADPH oxidase activity and p47phox expression. RESULTS: In an
Ashkenazi couple expecting a baby, both parents were found to be heterozygotes
for this mutation, as was the fetus. However, segregation analysis in the
extended family was consistent with the fetus inheriting both carrier alleles
from the parents. MLPA indicated four complete NCF1 genes in the fetus and three
in each parent. Gene sequencing confirmed these results. Analysis of fetal
leucocytes obtained by cordocentesis revealed substantial oxidase activity with
three different assays, which was confirmed after birth. In six additional
Ashkenazi carriers of the NCF1 c.579G>A mutation, we found five individuals with
three complete NCF1 genes of which one was mutated (like the parents), and one
individual with in addition a fusion gene of NCF1 with a pseudogene. CONCLUSION:
These results point to the existence of a 'false-carrier' state in Ashkenazi Jews
and have wide implications regarding pre-pregnancy screening in this and other
population groups.
PMID- 29331983
TI - Ophthalmoscopy skills in primary care: a cross-sectional practitioner survey.
PMID- 29331984
TI - Response to: 'Psychosocial job stressors and suicidality: a meta-analysis and
systematic review' by Milner et al.
PMID- 29331985
TI - Repair for rheumatic mitral valve disease. The controversy goes on!
PMID- 29331989
TI - Learning framework for implementing best evidence.
PMID- 29331988
TI - Airflow limitation in people living with HIV and matched uninfected controls.
AB - INTRODUCTION: Whether HIV influences pulmonary function remains controversial. We
assessed dynamic pulmonary function in people living with HIV (PLWHIV) and
uninfected controls. METHODS: A total of 1098 PLWHIV from the Copenhagen Co
morbidity in HIV infection study and 12 161 age-matched and sex-matched controls
from the Copenhagen General Population Study were included. Lung function was
assessed using FEV1 and FVC, while airflow limitation was defined by the lower
limit of normal (LLN) of FEV1/FVC and by FEV1/FVC<0.7 with FEV1predicted <80%
(fixed). Logistic and linear regression models were used to determine the
association between HIV and pulmonary function adjusting for potential
confounders (including smoking and socioeconomic status). RESULTS: In
predominantly white men with mean (SD) age of 50.6 (11.1) the prevalence of
airflow limitation (LLN) was 10.6% (95% CI 8.9% to 12.6%) in PLWHIV and 10.6%
(95% CI 10.0 to 11.1) in uninfected controls. The multivariable adjusted OR for
airflow limitation defined by LLN for HIV was 0.97 (0.77-1.21, P<0.78) and 1.71
(1.34-2.16, P<0.0001) when defined by the fixed criteria. We found no evidence of
interaction between HIV and cumulative smoking in these models (P interaction:
0.25 and 0.17 for LLN and fixed criteria, respectively). HIV was independently
associated with 197 mL (152-242, P<0.0001) lower FEV1 and 395 mL (344-447,
P<0.0001) lower FVC, and 100 cells/mm3 lower CD4 nadir was associated with 30 mL
(7-52, P<0.01) lower FEV1 and 51 mL (24-78, P<0.001) lower FVC. CONCLUSION: HIV
is a risk factor for concurrently decreased FEV1 and FVC. This excess risk is not
explained by smoking or socioeconomic status and may be mediated by prior
immunodeficiency. TRIAL REGISTRATION NUMBER: NCT02382822.
PMID- 29331986
TI - Sex differences in impact of coronary artery calcification to predict coronary
artery disease.
AB - OBJECTIVE: To assess sex-specific differences regarding use of conventional risks
and coronary artery calcification (CAC) to detect coronary artery disease (CAD)
using coronary CT angiography (CCTA). METHODS: The Nationwide Gender-specific
Atherosclerosis Determinants Estimation and Ischemic Cardiovascular Disease
Prospective Cohort study is a prospective, multicentre, nationwide cohort study.
Candidates with suspected CAD aged 50-74 years enrolled from 2008 to 2012. The
outcome was obstructive CAD defined as any stenosis >=50% by CCTA. We constructed
logistic regression models for obstructive CAD adjusted for conventional risks
(clinical model) and CAC score. Improvement in discrimination beyond risks was
assessed by C-statistic; net reclassification index (NRI) for CAD probability of
low (<30%), intermediate (30%-60%) and high (>=60%); and risk stratification
capacity. RESULTS: Among 991 patients (456 women, 535 men; 65.2 vs 64.4 years
old), women had lower CAC scores (median, 4 vs 60) and lower CAD prevalence
(21.7% vs 37.0%) than men. CAC significantly improved model discrimination
compared with clinical model in both sexes (0.66-0.79 in women vs 0.61-0.83 in
men). The NRI for women was 0.33, which was much lower than that for men (0.71).
Adding CAC to clinical model had a larger benefit in terms of moving an
additional 43.3% of men to the most determinant categories (high or low risk)
compared with -1.4% of women. CONCLUSIONS: The addition of CAC to a prediction
model based on conventional variables significantly improved the classification
of risk in suspected patients with CAD, with sex differences influencing the
predictive ability. TRIAL REGISTRATION NUMBER: UMIN-CTR Clinical Trial:
UMIN000001577.
PMID- 29331990
TI - Changes in the legal environment and enforcement of firearm transfer laws in
Pennsylvania and Maryland.
AB - The effectiveness of laws depends on circumstances affecting their enforcement.
To assess such circumstances for comprehensive background check (CBC) and straw
purchase laws for firearm sales, we examined prosecutions for CBC and straw
purchase violations in Pennsylvania and CBC violations in Maryland. We generated
pre-post variables and conducted t-tests to assess differences in the mean number
of prosecutions filed following changes to the legal environments. The annual
number of prosecutions for straw purchase violations increased significantly in
Pennsylvania following the passage of a law that strengthened penalties for these
violations (difference in means = +1310.86, P=0.003). The annual number of
prosecutions for CBC violations decreased significantly in Maryland following a
court decision that narrowed the definition of a firearm transfer making
enforcement more difficult (difference in means = -20.52, P=0.026). Our findings
suggest enforcement is likely influenced by the penalties associated with
violating these laws and the interpretation of the language of the laws.
PMID- 29331991
TI - Gauging the impact of gun background checks.
PMID- 29331992
TI - Effectiveness of interventions for reducing non-occupational sedentary behaviour
in adults and older adults: a systematic review and meta-analysis.
AB - BACKGROUND: No systematic reviews of the effectiveness of interventions for
reducing non-occupational sedentary behaviour are available. Therefore, the aim
of this systematic review was to assess the effectiveness of interventions for
reducing non-occupational sedentary behaviour in adults and older adults.
METHODS: An electronic search of nine databases was performed. Randomised
controlled trials (RCT) and cluster RCTs among adults testing the effectiveness
of interventions aimed to reduce non-occupational sedentary behaviour were
considered for inclusion. Two review authors independently screened studies for
eligibility, completed data extraction and assessed the risk of bias. RESULTS:
Nineteen studies that evaluated multicomponent lifestyle interventions,
counselling or education, television (TV) control devices and workplace
interventions were included. Evidence from the meta-analyses suggested that
interventions can reduce leisure sitting time in adults in the medium term (-30
min/day; 95% CI -58 to -2), and TV viewing in the short term (-61 min/day; 95% CI
-79 to -43) and medium term (-11 min/day; 95% CI -20 to -2). No significant
pooled effects were found for transport sitting time, leisure-time computer use
and longer term outcomes. No evidence was available on the effectiveness of
interventions for reducing non-occupational sedentary time in older adults.
CONCLUSIONS: The findings of this systematic review suggest the interventions may
be effective in reducing non-occupational sedentary behaviour in the short to
medium term in adults. However, no significant effect was found on longer term
outcomes. The quality of evidence was, however, low to very low. No evidence was
available on the effectiveness of non-occupational interventions on reducing
sedentary time in older adults. Further high-quality research with larger samples
is warranted.
PMID- 29331993
TI - Increased leisure-time physical activity associated with lower onset of diabetes
in 44 828 adults with impaired fasting glucose: a population-based prospective
cohort study.
AB - AIMS: To evaluate the effects of habitual leisure-time physical activity (LTPA)
on incident type 2 diabetes in a prospective cohort of Chinese adults with
impaired fasting glucose (IFG). METHODS: 44 828 Chinese adults aged 20-80 years
with newly detected IFG but free from cardiovascular and cerebrovascular disease
were recruited and followed up from 1996 to 2014. Incident type 2 diabetes was
identified by fasting plasma glucose >=7 mmol/L. The participants were classified
into four categories based on their self-reported weekly LTPA: inactive, low,
moderate, or high. Hazard ratios (HRs) and population attributable fractions
(PAFs) were estimated with adjustment for established diabetic risk factor.
RESULTS: After 214 148 person-years of follow-up, we observed an inverse dose
response relationship between LTPA and diabetes risk. Compared with inactive
participants, diabetes risk in individuals reporting low, moderate and high
volume LTPA were reduced by 12% (HR 0.88, 95% CI 0.80 to 0.99; P=0.015), 20% (HR
0.80, 95% CI 0.71 to 0.90; P<0.001), and 25% (HR 0.75, 95% CI 0.67 to 0.83;
P<0.001), respectively. At least 19.2% (PAF 19.2%, 95% CI 5.9% to 30.6%) of
incident diabetes cases could be avoided if the inactive participants had engaged
in WHO recommendation levels of LTPA. This would correspond to a potential
reduction of at least 7 million diabetic patients in the Greater China area.
CONCLUSIONS: Our results show higher levels of LTPA are associated with a lower
risk of diabetes in IFG subjects. These data emphasise the urgent need for
promoting physical activity as a preventive strategy against diabetes to offset
the impact of population ageing and the growing obesity epidemic.
PMID- 29331994
TI - ACL and meniscal injuries increase the risk of primary total knee replacement for
osteoarthritis: a matched case-control study using the Clinical Practice Research
Datalink (CPRD).
AB - OBJECTIVES: The aim of this study was to investigate whether ACL injury (ACLi) or
meniscal injury increases the risk of end-stage osteoarthritis (OA) resulting in
total knee replacement (TKR). METHODS: A matched case-control study of all TKRs
performed in the UK between January 1990 and July 2011 and recorded in the
Clinical Practice Research Datalink (CPRD) was undertaken. The CPRD contains
longitudinal data on approximately 3.6 million patients. Two controls were
selected for each case of TKR, matched on age, sex and general practitioner
location as a proxy for socioeconomic status. Individuals with inflammatory
arthritis were excluded. The odds of having TKR for individuals with a CPRD
recorded ACLi were compared with those without ACLi using conditional logistic
regression, after adjustment for body mass index, previous knee fracture and
meniscal injury. The adjusted odds of TKR in individuals with a recorded meniscal
injury compared with those without were calculated. RESULTS: After exclusion of
individuals with inflammatory arthritis, there were 49 723 in the case group and
104 353 controls. 153 (0.31%) cases had a history of ACLi compared with 41
(0.04%) controls. The adjusted OR of TKR after ACLi was 6.96 (95% CI 4.73 to
10.31). 4217 (8.48%) individuals in the TKR group had a recorded meniscal injury
compared with 669 (0.64%) controls. The adjusted OR of TKR after meniscal injury
was 15.24 (95% CI 13.88 to 16.69). CONCLUSION: This study demonstrates that ACLi
is associated with a sevenfold increased odds of TKR resulting from OA. Meniscal
injury is associated with a 15-fold increase odds of TKR for OA.
PMID- 29331995
TI - Infographic: Trends in paediatric and adolescent ACL injuries.
PMID- 29331997
TI - Correction: A rare case of dual diagnosis in a 16-year-old girl with shortness of
breath.
PMID- 29331996
TI - Relevance of enlarged cardiophrenic lymph nodes in determining prognosis of
patients with advanced ovarian cancer.
AB - Ovarian cancer often presents at an advanced stage with widespread peritoneal
and/or extra-abdominal metastases. Complete cytoreduction is the mainstay of
treatment for disease confined to peritoneum. But in patients with distant
metastases, the role and rationale is less obvious. One of the the most common
sites of extra-abdominal disease is the cardiophrenic lymph node (CPLN). In this
paper, we described the management of a patient with International Federation of
Gynecology and Obstetrics (FIGO) stage IVB epithelial ovarian carcinoma and
widespread peritoneal and extra-abdominal metastases to the CPLN, who underwent
complete cytoreduction including excision of enlarged CPLN, following neoadjuvant
chemotherapy. We examined the literature to determine the prognostic value of
enlarged CPLN and their relevance in managing patients with advanced ovarian
cancer and found it as an adverse prognostic factor. Transdiaphragmatic excision
of CPLN is feasible without major complications. But as its correlation with
overall or progression-free survival is not yet evident, large-scale prospective
studies are warranted.
PMID- 29331998
TI - Torsion and rupture of a non-communicating rudimentary horn in a 17-week
gestation in a 16-year-old girl: lessons learnt.
AB - A unicornuate uterus with non-communicating rudimentary horn has always been
notorious and poses threat to continuation of pregnancy with dismal consequences.
We are reporting an interesting case of uterine malformation with a 90 degrees
rotation of uterine axis which ultimately ruptured during termination of
pregnancy. The rarity in our case was not only conception in non-communicating
horn but also the complete twisting of axis which made the pregnant horn come in
front of the non-gravid unicornuate uterus, mimicking normal pregnancy. The most
important lesson learnt is that if induction does not lead to cervical changes
and uterine contractions, one must consider atypical presentations of an
anomalous uterus as a possible differential before proceeding further.
PMID- 29331999
TI - Eighty-five-year-old man with mosaic attenuation on chest imaging.
PMID- 29332000
TI - How good are doctors at introducing themselves? #hellomynameis.
AB - BACKGROUND: This explorative study was triggered by the '#hellomynameis' campaign
initiated by Dr Kate Granger in the UK. Our objectives were twofold: first, to
measure rates of introduction in an Irish hospital setting by both consultant and
non-consultant hospital doctors. Second to establish whether such practices were
associated with patient perceptions of the doctor/patient interaction. METHOD: A
patient 'exit' survey was undertaken following doctor-patient consultations in
both acute (surgical and medical assessment units) and elective settings
(outpatient clinics). The survey was carried out over a 5-month period by three
trained clinical observers. RESULTS: A total of 353 patients were surveyed. There
were 253 outpatients and 100 inpatients surveyed. There were 121 outpatients
(47.8%) who attended a surgeon, 73 were medical (28.8%), while 59 (23.3%) were
divided between obstetrics, gynaecology and ophthalmology. One hundred acute
presentations were surveyed: 52% in the emergency department, 20% to the acute
medical assessment unit, 21% attended the acute surgical assessment unit and 7%
attended other specialties/departments. CONCLUSION: According to the returned
forms, 79% of doctors (n=279) introduced themselves to patients. Eleven per cent
(39) of doctors did not introduce themselves, and 8.5% of patients (30) were
unsure whether the doctor had introduced themselves. Five patients left their
response blank.Consultants were significantly more likely (P=0.02) to introduce
themselves or shake hands than non-consultant hospital doctors. Gender had no
bearing (P=0.43) on introductions or handshakes regardless of grade of
doctor.Three hundred and seventeen patients (89.7%) felt that an introduction had
made a positive difference to their healthcare visit. Thirty patients (8.5%) felt
it did not make a difference and 8 patients (2.2%) were unsure or failed to
answer.This study has highlighted the importance of introductions to patients.
Definite evidence of an introduction was documented in 79% of patients with 14.5%
either not receiving or could not recall whether an introduction had been made on
repeat visits. 6.5% stated that they did not receive an introduction.
PMID- 29332001
TI - Problem-solving in clinical practice: a baby who won't stop bleeding.
AB - Spontaneous bleeding in the neonatal period is an unusual presentation, and yet
one that can pose a challenge of both diagnosis and management to the general
paediatrician. This case chronicles the diagnostic journey of an 8-day-old baby
who presented with unrelenting bleeding from the umbilical cord and explores the
clinical approach to bleeding in a neonate.
PMID- 29332003
TI - What do I need to know about metronidazole?
PMID- 29332002
TI - The implementation of a cystic fibrosis annual review process in a tertiary
paediatric hospital.
AB - We evaluated the implementation of a cystic fibrosis annual review process in a
tertiary paediatric hospital. After implementation, there was demonstrated
improvement in an important outcome measure-the use of inhaled mucolytic agents.
PMID- 29332004
TI - Host-agent-vector-environment measures for electronic cigarette research used in
NIH grants.
AB - OBJECTIVE: The purpose of this study is to describe the focus and
comprehensiveness of domains measured in e-cigarette research. METHODS: A
portfolio analysis of National Institutes of Health grants focusing on e
cigarette research and funded between the fiscal years 2007 and 2015 was
conducted. Grant proposals were retrieved using a government database and coded
using the Host-Agent-Vector-Environment (HAVE) model as a framework to
characterise the measures proposed. Eighty-one projects met the criteria for
inclusion in the analysis. RESULTS: The primary HAVE focus most commonly found
was Host (73%), followed by Agent (21%), Vector (6%) and Environment (0%).
Intrapersonal measures and use trajectories were the most common measures in
studies that include Host measures (n=59 and n=51, respectively). Product
composition was the most common area of measurement in Agent studies (n=24),
whereas Marketing (n=21) was the most common (n=21) area of Vector measurement.
When Environment measures were examined as secondary measures in studies, they
primarily focused on measuring Peer, Occupation and Social Networks (n=18).
Although all studies mentioned research on e-cigarettes, most (n=52; 64%) did not
specify the type of e-cigarette device or liquid solution under study.
CONCLUSIONS: This analysis revealed a heavy focus on Host measures (73%) and a
lack of focus on Environment measures. The predominant focus on Host measures may
have the unintended effect of limiting the evidence base for tobacco control and
regulatory science. Further, a lack of specificity about the e-cigarette product
under study will make comparing results across studies and using the outcomes to
inform tobacco policy difficult.
PMID- 29332005
TI - Impact of a negative emotional antitobacco mass media campaign on French smokers:
a longitudinal study.
AB - BACKGROUND: Mass media campaigns to encourage smoking cessation have been shown
to be effective in a context of comprehensive tobacco control programme. The
effectiveness of antismoking ads that evoke negative emotions remains unclear, in
particular in countries with high smoking prevalence and among smokers with low
perceived susceptibility, low self-efficacy or who are not users of smoking
cessation services. OBJECTIVE: To evaluate short-term and long-term effects of a
1-month French national highly emotional media campaign, with a focus on these
specific targets. DESIGN: A 6-month longitudinal survey by Internet. A sample of
3000 smokers were interviewed before the media campaign (T0). They were contacted
again just after (T1) and 6 months after the campaign (T2). OUTCOMES: Perceived
susceptibility to the risks of smoking, self-efficacy to quit smoking, use of
smoking cessation services (quitline and website) and 7-day quitting. METHODS:
The analysis was carried out on 2241 individuals who answered at T1 and T2.
Multiple logistic regressions were computed to test the association between the
change in each outcome at T1 and T2 and the level of exposure based on self
reported recall. RESULTS: Self-reported recall was associated with an increase in
perceived susceptibility and with use of cessation services. Campaign recall was
also associated with higher 7-day quitting immediately after the campaign (OR=1.8
(1.0 to 3.2), P<0.05). CONCLUSIONS: Fear-appeal mass media campaigns can be
effective in encouraging cessation among smokers in a country with high smoking
prevalence (France), but should be accompanied by convincing self-efficacy
messages.
PMID- 29332006
TI - Global evidence on the effect of point-of-sale display bans on smoking
prevalence.
AB - BACKGROUND: Since Iceland became the first country to impose a ban on point-of
sale (POS) tobacco product displays in 2001, 20 countries have implemented POS
display bans as of 2016. This study examined the effect that POS display bans
have on smoking prevalence. METHODS: Data were sourced from Euromonitor
International and the WHO MPOWER package for 2007-2014 from 77 countries
worldwide. generalised linear models with country and year fixed effects were
estimated to analyse the effect of POS display bans on smoking prevalence.
RESULTS: Having a POS display ban reduced overall adult daily smoking, male
smoking and female smoking by about 7%, 6% and 9%, respectively. CONCLUSIONS:
Having a POS display ban is likely to reduce smoking prevalence and generate
public health benefits.
PMID- 29332007
TI - Impacts of Canada's minimum age for tobacco sales (MATS) laws on youth smoking
behaviour, 2000-2014.
AB - BACKGROUND: Recently, the US Institute of Medicine has proposed that raising the
minimum age for tobacco purchasing/sales to 21 years would likely lead to
reductions in smoking behavior among young people. Surprisingly few studies,
however, have assessed the potential impacts of minimum-age tobacco restrictions
on youth smoking. OBJECTIVE: To estimate the impacts of Canadian minimum age for
tobacco sales (MATS) laws on youth smoking behaviour. DESIGN: A regression
discontinuity design, using seven merged cycles of the Canadian Community Health
Survey, 2000-2014. PARTICIPANTS: Survey respondents aged 14-22 years (n=98 320).
EXPOSURE: Current Canadian MATS laws are 18 years in Alberta, Saskatchewan,
Manitoba, Quebec, the Yukon and Northwest Territories, and 19 years of age in the
rest of the country. MAIN OUTCOMES: Current, occasional and daily smoking status;
smoking frequency and intensity; and average monthly cigarette consumption.
RESULTS: In comparison to age groups slightly younger than the MATS, those just
older had significant and abrupt increases immediately after the MATS in the
prevalence of current smokers (absolute increase: 2.71%; 95% CI 0.70% to 4.80%;
P=0.009) and daily smokers (absolute increase: 2.43%; 95% CI 0.74% to 4.12%;
P=0.005). Average past-month cigarette consumption within age groups increased
immediately following the MATS by 18% (95% CI 3% to 39%; P=0.02). There was no
evidence of significant increases in smoking intensity for daily or occasional
smokers after release from MATS restrictions. CONCLUSION: The study provides
relevant evidence supporting the effectiveness of Canadian MATS laws for limiting
smoking among tobacco-restricted youth.
PMID- 29332008
TI - Leg stereotypy syndrome: phenomenology and prevalence.
AB - OBJECTIVES: To describe the phenomenology and prevalence of leg stereotypy
syndrome (LSS), characterised chiefly by repetitive, rhythmical, stereotypic leg
movement, especially when sitting. METHODS: We sought to characterise LSS in two
groups of subjects: (1) general population (GP) group, defined as individuals
accompanying patients during their visits to Baylor College of Medicine
Parkinson's Disease Center and Movement Disorders Clinic who are not genetically
related to the patients; and (2) movement disorders (MD) group, composed of
consecutive patients with diagnoses of restless legs syndrome, Parkinson's
disease, Tourette syndrome and tardive dyskinesia. RESULTS: There were 92
participants enrolled in this study; 7% of 57 individuals in the GP group and 17%
of those in the MD group met the diagnostic criteria for LSS. The mean age of
individuals with LSS was 44.5 (+/-11.9) years and mean age at onset of LSS was
17.5 (+/-5.7) years. In half of the individuals, the 'shaking' involved
predominantly one leg. All had a positive family history of similar disorder and
none had diurnal variation. The seven-item Leg Stereotypy Syndrome Questionnaire
was developed as a screening tool to aid in differentiating LSS from other
movement disorders. CONCLUSIONS: LSS is a common condition, occurring in up to 7%
of otherwise healthy individuals, and it is even more common in patients with
hyperkinetic movement disorders. Although it phenomenologically may overlap with
other stereotypic disorders, we argue that it is a distinct, familial,
neurological syndrome.
PMID- 29332009
TI - Poststroke psychosis: a systematic review.
AB - A preregistered systematic review of poststroke psychosis examining clinical
characteristics, prevalence, diagnostic procedures, lesion location, treatments,
risk factors and outcome. Neuropsychiatric outcomes following stroke are common
and severely impact quality of life. No previous reviews have focused on
poststroke psychosis despite clear clinical need. CINAHL, MEDLINE and PsychINFO
were searched for studies on poststroke psychosis published between 1975 and
2016. Reviewers independently selected studies for inclusion, extracted data and
rated study quality. Out of 2442 references, 76 met inclusion criteria. Average
age for poststroke psychosis was 66.6 years with slightly more males than females
affected. Delayed onset was common. Neurological presentation was typical for
stroke, but a significant minority had otherwise 'silent strokes'. The most
common psychosis was delusional disorder, followed by schizophrenia-like
psychosis and mood disorder with psychotic features. Estimated delusion
prevalence was 4.67% (95% CI 2.30% to 7.79%) and hallucinations 5.05% (95% CI
1.84% to 9.65%). Twelve-year incidence was 6.7%. No systematic treatment studies
were found. Case studies frequently report symptom remission after
antipsychotics, but serious concerns about under-representation of poor outcome
remain. Lesions were typically right hemisphere, particularly frontal, temporal
and parietal regions, and the right caudate nucleus. In general, poststroke
psychosis was associated with poor functional outcomes and high mortality. Poor
methodological quality of studies was a significant limitation. Psychosis
considerably adds to illness burden of stroke. Delayed onset suggests a window
for early intervention. Studies on the safety and efficacy of antipsychotics in
this population are urgently needed.
PMID- 29332010
TI - Oligogenic genetic variation of neurodegenerative disease genes in 980 postmortem
human brains.
AB - BACKGROUND: Several studies suggest that multiple rare genetic variants in genes
causing monogenic forms of neurodegenerative disorders interact synergistically
to increase disease risk or reduce the age of onset, but these studies have not
been validated in large sporadic case series. METHODS: We analysed 980
neuropathologically characterised human brains with Alzheimer's disease (AD),
Parkinson's disease-dementia with Lewy bodies (PD-DLB), frontotemporal dementia
amyotrophic lateral sclerosis (FTD-ALS) and age-matched controls. Genetic
variants were assessed using the American College of Medical Genetics criteria
for pathogenicity. Individuals with two or more variants within a relevant
disease gene panel were defined as 'oligogenic'. RESULTS: The majority of
oligogenic variant combinations consisted of a highly penetrant allele or known
risk factor in combination with another rare but likely benign allele. The
presence of oligogenic variants did not influence the age of onset or disease
severity. After controlling for the single known major risk allele, the frequency
of oligogenic variants was no different between cases and controls. CONCLUSIONS:
A priori, individuals with AD, PD-DLB and FTD-ALS are more likely to harbour a
known genetic risk factor, and it is the burden of these variants in combination
with rare benign alleles that is likely to be responsible for some oligogenic
associations. Controlling for this bias is essential in studies investigating a
potential role for oligogenic variation in neurodegenerative diseases.
PMID- 29332011
TI - Examining the utility of cystatin C as a confirmatory test of chronic kidney
disease across the age range in middle-aged and older community-dwelling adults.
AB - BACKGROUND: Cystatin C has been proposed as a confirmatory test of chronic kidney
disease (CKD). This is most applicable to older individuals with CKD, the
majority of whom have a creatinine-based estimated glomerular filtration rate
(eGFR) of 45-59 mL/min/1.73 m2 (CKD stage 3a). We sought to examine the utility
of cystatin C as a confirmatory test of CKD across the age range in the general
population of older adults. METHODS: Cross-sectional analysis of 5386
participants from The Irish Longitudinal Study on Ageing, a cluster-sampled
national cohort of community-dwelling adults aged >=50 years. Cystatin C and
creatinine were measured simultaneously using standardised assays. Using
generalised additive models, we modelled the distributions of creatinine and
cystatin C per year of age from four distributional parameters: location,
dispersion, skewness, kurtosis. Among participants with CKD stage 3a, we
estimated the predicted probability of cystatin C eGFR <60 mL/min/1.73 m2
('confirmed CKD') as a function of age. RESULTS: Median age was 62 years, 53%
were female and median cystatin C eGFR was 80 mL/min/1.73 m2. We observed
progressive variability in cystatin C with increasing age. Compared with
creatinine, cystatin C levels rose sharply beyond the age of 65. Among
participants with CKD stage 3a (n=463), the predicted probability of 'confirmed
CKD' increased steadily with age, from 15% at age 50 to 80% at age 80.
CONCLUSIONS: The clinical utility of cystatin C may be maximised in middle-aged
individuals, in whom the distribution of cystatin C is less variable than older
adults, and the pretest probability of confirming CKD is lower.
PMID- 29332013
TI - Patterns and predictors of disclosure of HIV positive status among youth living
with HIV in Ibadan, Nigeria.
AB - Background Information on disclosure of HIV status among youth is sparse in spite
of the fact that they bear a significant burden of the HIV epidemic. Our
objective was to determine the predictors of HIV disclosure among youth aged 18
35 years in Ibadan, Nigeria. Methods A cross-sectional study was conducted among
youth with HIV attending two HIV support groups and one ARV clinic in Ibadan,
Nigeria. Information was obtained with the aid of an interviewer-administered
questionnaire. Descriptive and analytic statistics were conducted. Results There
were 170 clients with a mean age of 29.6 +/- 3.9 years; 140 (82.4%) were female
and 139 (81.8%) had disclosed their status. Common people first informed included
respondents' mother 49 (35.3%), spouse 39 (28.1%) or father, 38 (27.3%).
Disclosure to an unmarried sexual partner was low as only six (12.0%) of the 50
single youth who had a current sexual partner had disclosed their status to
him/her. Youth who were aware that their spouse/partner was HIV positive (OR =
9.87; CI = 1.09-88.83) or negative (OR = 9.98; CI = 1.18-84.70) were more likely
to have disclosed their status than those unaware of their spouse/partners'
status. Disclosure was also higher among members of an HIV support group (OR =
3.32; CI = 1.03-10.72). Conclusions Many respondents had disclosed their status
although disclosure to an unmarried sexual partner was low. Interventions to
improve HIV disclosure especially among unmarried sexually active youth could
improve disclosure and overall management of HIV in our study area.
PMID- 29332012
TI - Classical (adiponectin, leptin, resistin) and new (chemerin, vaspin, omentin)
adipocytokines in patients with prediabetes.
AB - Background In the last decade, there has been an increased interest toward fat
tissue as an endocrine organ that secretes many cytokines and bioactive mediators
that play a role in insulin sensitivity, inflammation, coagulation and the
pathogenesis of atherosclerosis. The aim of this study was to investigate
classical (adiponectin, leptin, resistin) and new (chemerin, vaspin, omentin)
adipocytokine levels in subjects with prediabetes [impaired fasting glucose (IFG)
and/or impaired glucose tolerance (IGT)] and obese subjects with normoglycemia.
Methods In this study, 80 patients with a mean age of 50.4 +/- 10.6 years were
recruited, divided into two groups with similar age and body mass index (BMI) -
with obesity and normoglycemia (n = 41) and with obesity and prediabetes (n =
39). Results Serum adiponectin levels were significantly higher in subjects with
normoglycemia compared to patients with prediabetes. Adiponectin has a good
discriminating power to distinguish between patients with and without insulin
resistance in our study population [area under the curve (AUC) = 0.728, p =
0.002]. Other adipocytokine levels were not significantly different between the
two groups. The patients with metabolic syndrome (MetS) had significantly lower
levels of leptin compared to those without MetS (33.03 +/- 14.94 vs. 40.24 +/-
12.23 ng/mL) and this difference persisted after adjustment for weight and BMI.
Receiver operating characteristic (ROC) analysis showed that low serum leptin can
predict the presence of MetS (p = 0.03), AUC = 0.645. Conclusion Serum
adiponectin is statistically higher in patients with normoglycemia compared to
those with prediabetes and has a predictive value for distinguishing between
patients with and without insulin resistance in the studied population. Serum
leptin has a good predictive value for distinguishing between patients with and
without MetS in the studied population.
PMID- 29332014
TI - Influence of waist circumference on blood pressure status in non-obese
adolescents.
AB - Objectives To check whether excess in abdominal adiposity and metabolic factors
were associated with blood pressure abnormalities in non-obese adolescents.
Methods We randomly selected 1100 adolescent students, aged 12-18 years, from
schools and classrooms in the city of Constantine, Algeria. Among them 179 were
overweight and 51 were obese (IOTF criteria). Waist circumference (WC) was
considered high if >74 cm in boys and 75 cm in girls (mean of WC of all
population studied). Hypertension (HBP) and prehypertension (preHBP) were defined
by the NHBPEP's 2004 criteria. Results The prevalence of HBP/preHBP were
13.0%/12.4% with no difference between boys and girls. The percentages of
HBP/preHBP patients were 15.6%/15.6% in overweight adolescents, 5.9%/31.4% in
obese adolescents and 12.9%/10.6% in adolescents with normal body weight (p <
0.0001). In obese adolescents, the prevalence of HBP was higher among boys than
girls (36% vs. 27%, p = 0.002). In normal and overweight adolescents, the
prevalence of HBP and preHBP was similar in boys and girls (11.9% vs. 11.0% and
14.7% vs. 12.1%); the association of WC (high vs. not high) with HBP was found in
boys (16.1% vs. 8.8%, p = 0.009) but not in girls (12.1% vs. 10.2%), and with
preHBP in girls (15.5% vs. 8.0%, p = 0.029) but not in boys (16.2% vs. 13.6%).
Waist circumference [OR: 1.04 (1.03-1.06); p < 0.0001] and HOMA index [OR: 1.65
(1.13-2.39); p = 0.009] were associated with an increased risk of HBP. Conclusion
In non-obese adolescents, a high WC, defined by values over the mean WC observed
in our population, is associated with a higher risk of HBP in boys.
PMID- 29332015
TI - Post-traumatic stress and growth among CPR survivors in the southeast of Iran.
AB - Background Almost 7.2%-10.6% of patients survive CPR in Iran. Most of them
experience post-traumatic stress disorder (PTSD) and post-traumatic growth (PTG).
There are limited studies to assessing the correlation between these two
psychological outcomes among CPR survivors. Objective This study aimed to examine
the correlation between PTSD and PTG among CPR survivors in South-East Iran.
Subjects Using Quota sampling, 163 CPR survivors in two provinces in the South
East of Iran were selected to participate in this study. Method A descriptive
correlational study was used to fulfill the aim of the study. The impact of Event
Scale-Revised (IES-R) for assessing PTSD and Post-traumatic growth questionnaires
were used to assess PTG. Results The mean score of PTSD was 39.89 and according
to the cutoff point, 87.1% of participants suffered from PTSD. The mean score of
PTG was 78.6. PTSD and PTG had significant negative correlation. The result of
multi-variate logistic regression showed that only the PTG score predicted PTSD
(Odds ratio = 0.79, CI = 0.72-0.87; and p < 0.001). The result of multi-variate
linear regression indicated that PTSD, time passed since CPR, and physical
disability caused by CPR predicted PTG score significantly. Conclusion This study
provides CPR survivors and health care personnel with some valuable insights
about cultural aspects of PTSD and PTG among CPR survivors and that PTG is
positively influenced by physical disability and time passed since CPR. CPR
survivors may gain positive experience and valuable insight in group meetings and
discussions with their counterparts.
PMID- 29332016
TI - Tribute to a giant: Emanuel Chigier, MD, 1928-2017.
PMID- 29332017
TI - Insulin resistance and lung function in obese asthmatic pre-pubertal children.
AB - BACKGROUND: Recent findings have supposed that the underlying association between
the increased prevalence of both asthma and obesity may be insulin resistance
(IR). METHODS: Insulin and glucose serum levels were analyzed to calculate the
homeostatic model assessment of insulin resistance (HOMA-IR) for IR in 98 pre
pubertal children. Lung function and allergy status evaluation were performed.
The study population was divided into four groups: (1) obese asthmatic children
(ObA); (2) normal-weight asthmatic children (NwA); (3) normal-weight non
asthmatic children (Nw) and (4) obese non-asthmatic children (Ob). RESULTS:
Forced expiratory volume in 1 s (FEV1) was slightly lower in obese subjects
compared with normal-weight subjects and forced vital capacity (FVC) appeared
lower in asthmatics, whereas between non-asthmatics subjects, it was lower in the
obese group than in the normal-weight one. The post hoc analysis revealed a
statistically significant reduction in FEV1, peak expiratory flow (PEF), forced
expiratory flows (FEF) between 50% and 25% of the FVC (FEF50 and FEF25) between
ObA and Nw and in FEV1, FVC, PEF, FEF50 and FEF25 between NwA and Nw, but no
statistically significant differences of lung function parameters were observed
between ObA and NwA. We found an inverse relationship between HOMA-IR and all
spirometric parameters, although without any statistical significance. We also
observed a significantly lower FVC in insulin-resistant children (HOMA-IR>95th
percentile) (p=0.03). CONCLUSIONS: This study suggests that lung function could
be early altered in obese children, already in pre-pubertal age. Although IR
should not manifest its effects on lungs in pre-pubertal obese children, the
prevention or treatment of obesity in the pre-pubertal period may prevent
definitive negative effects on lungs.
PMID- 29332018
TI - The Epidemic of Obesity.
AB - No Abstract Available.
PMID- 29332019
TI - A Review of the Evolution of Ayurveda in the United States.
AB - No Abstract Available.
PMID- 29332021
TI - The Effects of Reflexology on Fatigue and Anxiety in Patients With Multiple
Sclerosis.
AB - Context * Multiple sclerosis (MS) is an inflammatory, demyelinating disease of
the central nervous system. In addition to the progressive nature of the disease,
devastating symptoms adversely affect the patient's daily life and future
expectations. This situation leads patients to seek complementary and alternative
treatments. Objectives * This study was conducted to determine the effects of
reflexology on fatigue severity and anxiety in patients with MS. Design * The
research was a quasi-experimental, pretest-posttest design. Setting * The
research was conducted at the Mavi Isiklar Rehabilitation Center of the
Metropolitan Municipality of Samsun (Samsun, Turkey), in cooperation with the
Faculty of Medicine's Hospital Neurology Clinic and the Health Application and
Research Center at Ondokuz Mayis University (Samsun, Turkey), and with the Black
Sea MS Association. Participants * Participants were patients who participated in
the MS Patient School program at the center and who had been diagnosed with MS at
least 1 y prior to the start of the study. Inventions * Reflexology was applied
for 60 min, 30 min for each leg. Reflexology was conducted in an ergonomic and
positionable bed in a special physiotherapy room within the Mavi Isiklar resting
facilities. Outcome Measures * Sociodemographic data forms, a fatigue severity
scale (FSS), and a state-trait anxiety inventory (STAI) were used in the data
collection. Results * Fifteen patients participated in the study. The average age
of the participants was determined to be 39.20 +/- 11.89 y. Before the
participants received reflexology, the average FSS score was 40.06 +/- 19.27; the
mean (+/-SD) STAI-S score was 50.33 +/- 9.48; and the mean (+/-SD) STAI-T score
was 43.33 +/- 9.48. The average FSS score after reflexology was 27.66 +/- 21.23;
the mean (+/-SD) STAI-S score was 37.53 +/- 10.11; and the mean (+/-SD) STAI-T
score was 31.86 +/- 10.27. Conclusions * The study indicates that reflexology can
be an effective method for reducing fatigue severity and anxiety in patients with
MS.
PMID- 29332022
TI - Comparative Antitussive Effects of Medicinal Plants and Their Constituents.
AB - Context * The cough is a protective reflex, with 2 types, one being more
sensitive to mechanical stimulation and the other to chemical stimulation, such
as sulfur dioxide, ammonia, citric acid, and capsaicin. Some evidence is
available that suppressant therapy is most effective when used for the short-term
reduction of coughing. Today, use of herbal drugs is increasing all over the
world for various ailments, including to provide antitussive activity. Objective
* The study intended to review the antitussive effects of various extracts, some
fractions, and some constituents of the studied medicinal plants. Design *
Various databases, including the Medline, Science Direct, Scopus, and Google
Scholar, were searched for studies published between 1978 and 2015, using the
keywords antitussive and cough and the names of various medicinal plants and
their constituents. Setting * The study took place in the districts related to
Mashhad University of Medical Sciences (Mashhad, Iran). Outcome Measures * The
antitussive effects of medicinal plants and their constituents were normalized to
50 mg/kg and 1 mg/mL against various cough stimulants and compared. Results * The
most potent antitussive effect was observed for Nigella sativa and Linum
usitatissimum on coughs induced by sulfur dioxide. Artemisia absinthium showed a
higher antitussive effect on cough induced by ammonia compared with the other
studied medicinal plants. The antitussive effects of Cuminum cyminum and
Glycyrrhiza glabra were more potent on cough induced by citric acid than other
medicinal plants. Conclusions * These results suggest the therapeutic potential
of the studied medicinal plants as antitussive therapies. However, only a few
clinical studies have examined the antitussive effects of medicinal plants, and
more clinical studies are needed. The underlying mechanisms of the antitussive
effects of medicinal plants should be also examined in further studies.
PMID- 29332020
TI - Predictors of Improvements in Mental Health From Mindfulness Meditation in
Stressed Older Adults.
AB - Context * The benefits of a mindfulness meditation (MM) intervention are most
often evidenced by improvements in self-rated stress and mental health. Given the
physiological complexity of the psychological stress system, it is likely that
some people benefit significantly, whereas others do not. Clinicians and
researchers could benefit from further exploration to determine which baseline
factors can predict clinically significant improvements from MM. Objectives * The
study intended to determine (1) whether the baseline measures for participants
who significantly benefitted from MM training were different from the baseline
measures of participants who did not, and (2) whether a classification analysis
using a decision-tree, machine-learning approach could be useful in predicting
which individuals would be most likely to improve. Design * The research team
performed a secondary analysis of a previously completed randomized, controlled
clinical trial. Setting * The study occurred at the Oregon Health & Science
University (Portland, OR, USA) and in participants' homes. Participants *
Participants were 134 stressed, generally healthy adults from the metropolitan
area of Portland, Oregon, who were 50 to 85 y old. Intervention * Participants
were randomly assigned either to a 6-wk MM intervention group or to a waitlist
control group, who received the same MM intervention after the waitlist period.
Outcome Measures * Outcome measures were assessed at baseline and at 2-mo follow
up intervals. A responder was defined as someone who demonstrated a moderate,
clinically significant improvement on the mental health component (MHC) of the
short-form health-related quality of life (SF-36) (ie, a change >=4). The MHC had
demonstrated the greatest effect size in the primary analysis of the previously
mentioned randomized, controlled clinical trial. Potential predictors were
demographic information and baseline measures related to stress and affect.
Univariate statistical analyses were performed to compare the values of
predictors in the responder and nonresponder groups. In addition, predictors were
chosen for a classification analysis using a decision tree approach. Results * Of
the 134 original participants, 121 completed the MM intervention. As defined
previously, 61 were responders and 60 were nonresponders. Analyses of the
baseline measures demonstrated significant differences between the 2 groups in
several measures: (1) the positive and negative affect schedule negative subscale
(PANAS-neg), (2) the SF-36-MHC, and (3) the SF-36 energy/fatigue, with clinically
worse scores being associated with greater likelihood of being a responder.
Disappointingly, the decision-tree analyses were unable to achieve a
classification rate of better than 65%. Conclusions * The differences in
predictor variables between responders and nonresponders to an MM intervention
suggested that those with worse mental health at baseline were more likely to
improve. Decision-tree analysis was unable to usefully predict who would respond
to the intervention.
PMID- 29332023
TI - Autonomic Response Testing Compared With Immunoglobulin E Allergy Panel Test
Results: Preliminary Report.
AB - Context * Chronically ill patients who have failed standard medical assessment
and therapies are often assessed by integrative medical providers for atypical
manifestations of allergies as the possible source or contributing factor(s) to
their condition. Skin testing and immunoglobulin E (IgE) allergy panels increase
the cost of care in these patients. Objective * The objective of this study was
to determine the accuracy of autonomic response testing (ART) as compared with
IgE allergy panel blood tests. Design * This study was a retrospective chart
review of patients who had ART and blood drawn for an IgE allergy panel at the
same office visit. Outcome Measures * Sensitivity, specificity, positive
predictive value, negative predictive value, overall accuracy, phi coefficient,
and Cohen's kappa were calculated. Results * A total of 14 charts were reviewed.
All measures of accuracy were of either useful or excellent strength. The
strength of association measures of the phi coefficient and Cohen's kappa were
strong. Conclusion * This first and preliminary evaluation of the allergy
assessment utility of ART is very promising and reveals the need for more
vigorous follow-up studies.
PMID- 29332024
TI - The Effects of Apotel and Remifentanil on Postoperative Pain.
AB - Context * One of the most common complications of a Caesarean section (C-section)
is postoperative inflammation as well as operative and postoperative pain
associated with the surgery. The control and mitigation of pain after surgery is
the main goal of anesthesiologists. Objectives * This study aimed to compare the
effects of intravenous apotel and remifentanil on postoperative pain control in
women undergoing an elective C-section. Design * The research team designed a
single-blinded, randomized clinical trial. Setting * The study was performed at
the Taleghani Hospital (Arak, Iran). Participants * Potential participants were
70 patients undergoing an elective C-section. Intervention * Participants were
divided randomly into 2 groups, the apotel (A) and remifentanil (R) groups, with
35 participants in each group. The participants in the A group received an
infusion of 1 g of apotel to 200 cc of normal saline for 20 min, after
anesthesia, the removal of their fetuses, and the clamping of their umbilical
cords. The same procedure was followed for the R group (ie, the participants
received an infusion of 0.5 MUg of remifentanil per kg of body weight per minute
after anesthesia), removal of their fetuses, and clamping of their umbilical
cords. Outcome Measures * Pain scores were measured 3 times using a visual
analogue scale during the recovery period (from anesthesia and pain scores) and
at 4 and 12 h after surgery after surgery. Participants' use of narcotics during
the 24 h after surgery was recorded. Data analysis was done using SPSS (version
16) statistical software. Results * The pain scores of the R group were lower
than those of the A group during the recovery period and a statistically
significant difference existed between the pain scores of the 2 groups during
that period (P = .01). No statistically significant difference existed between
the groups in participants' mean use of narcotic drugs during the 24 h of
surgery. Moreover, no statistically significant differences were found between
the groups in participants' blood pressures or heart rates during the recovery
period or at 4 and 12 h after surgery (P >= .05). Conclusion * Remifentanil can
provide better postoperative pain control than apotel immediately after surgery.
PMID- 29332025
TI - Prolegomena to a True Integrative Medical Paradigm.
AB - When a paradigm starts to show signs of failure to cope with significant
questions in any basic/applied branch of human knowledge, there come on the scene
those who have perused the related literature enough to either answer those major
questions according to the established paradigm or proffer a (wholly) new way of
looking at things. In the latter case, the history of science tells us, a
paradigm shift takes place. Modern medicine cannot be proven to be totally
disconnected from its traditional roots. Where traditional medicine came to give
its place to present-day conventional medicine, a number of humanistic aspects of
healing, in addition to some axioms of old wisdom, were actually lost. Employing
a personalized strategy by considering the patient's specific conditions,
integrative medicine endeavors to apply all appropriate interventions from a
whole set of science branches to bring back health. However, this does not remain
fully without its own challenges from almost all sides. Complementary and
alternative medicine, on the one hand, and evidence-based medicine, on the other,
have their own rightful say in the affair. Delving deep into the details of
medical history's ups and downs, and examining-from the philosophy of medicine's
and philosophy of science's standpoints-the pros and cons of integrative
medicine, this present treatise makes a systemic, interdisciplinary effort to put
forward the best possible paradigmatology in a methodical way as far as the
demands of society are concerned.
PMID- 29332026
TI - Medicinal Plant Materials in the Treatment of Anxiety Disorders: Neurobiological
Aspects.
AB - Context * Pathological anxiety, which affects approximately one-third of the
world population, is an inadequate, irrational reaction of an organism to the
environment and to a potential threat. Despite advancements in pharmacotherapy
for anxiety disorders, further studies are still necessary to search for new
substances possessing the desired anxiolytic effects, with as few unwanted
effects as possible. Objective * This study intended to examine the
characteristics of medicinal plant materials that exhibit anxiolytic properties,
with a special emphasis on the mechanisms of action of their active ingredients
on the systems involved in the pathophysiology of anxiety. Design * The research
team performed a review of the literature, searching well-known online scientific
databases, including PubMed, Google Scholar, Medline, ScienceDirect, and
SpringerLink. The team searched for the newest research from various regions of
the world. Setting * The study was done in the Medical University of Silesia
(Katowice, Poland). Results * The medicinal plant materials presented in the
current article undoubtedly influence the central nervous system. Our analysis
showed that their mechanism of action is very complicated and appropriately still
enigmatic. Among them, V officinalis represents the most thoroughly investigated
medicinal plant material that produces anxiolytic, sedative effects. However,
extracts of other medicinal plants may also emerge as helpful in the treatment of
fear and anxiety and in the prophylaxis of those disorders. Conclusions * The
current review discusses the most recent data on medicinal plant materials that
are effective as anxiolytic treatments, with special emphasis on the
neurobiological mechanisms of action of their active ingredients. The research
team hopes that the information may open up new directions in the search for
drugs capable of enhancing the existing therapy.
PMID- 29332027
TI - Phyllodes tumors of the breast: clinicopathological analysis of 106 cases from a
single institution.
AB - BACKGROUND: Phyllodes tumors (PT) are uncommon biphasic tumors, accounting for
less than 1% of all breast primary neoplasms. They form a wide variety of tumors
ranging from benign to malignant. Several histological features are used to grade
PT into 3 categories: benign (grade I), borderline (grade II) and malignant
(grade III) tumors. The aim of our study was to analyse histolopathological,
radiological and clinical features of PT from an experience of a single center.
METHODS: It was a retrospective study including 106 patients diagnosed with
phyllodes tumors on surgical specimens at the department of pathology, of Hassan
II university hospital (Fez, Morocco), from 2009 to 2016. RESULTS: The mean age
was 33.81 years (range of 13-66 years), and the mean age increases with the tumor
grade (mean ages of 32.32, 32.87 and 33.65 years respectively for grade I, II and
III PT) (p = 0.023); 78 patients (73.58%) had benign PT, 20 (18.86%) had
borderline PT and 8 (7.54%) patients were diagnosed with malignant PT. Mostly,
the tumor size was <5 cm (63.2%), with BI-RADS 3 (51 patients, 48.11%). The tumor
size and the radiological suspicion (ACR/BI-RADS) increased with the tumor grade
(p < 0.001). Mitosis count, cellular atypia and stromal cellularity increased
with the tumor grade (p < 0.001). Also, the presence of necrosis is associated
with malignant PT (p < 0.001). Before surgery, patients had undergone core needle
biopsies (CNB) for diagnostic purpose, and the overral sensitivity of this
diagnostic procedure was 71.83%. The sentivity of the CNB decreased from grade I
PT to grade III PT (from 56.81% to 37.5%), however its specificity increased from
grade I to grade III PT (from 59.25% to 100%). CONCLUSION: Phyllodes tumors of
the breast are rare neoplasms with a wide range of clinicopathologic
presentations. The core needle biopsy has a good diagnostic sensitivity compared
to definitive diagnosis on surgical specimens. There was a statistically
significant association between the histological grade of PT and tumor size,
radiological suspicion, mitotic count, cellular atypia, stromal cellularity, and
tumor necrosis.
PMID- 29332028
TI - Possible erythrocyte contributions to and exacerbation of the post-thrombolytic
no-reflow phenomenon.
AB - BACKGROUND: Reperfusion injury often occurs with therapeutic intervention
addressing the arterial occlusions causing acute myocardial infarction and
stroke. The no-reflow phenomenon has been ascribed to leukocyte plugging and
blood vessel constriction in the microcirculation. OBJECTIVE: To assess possible
red cell contributions to post-thrombolytic no-reflow phenomenon. METHODS: Blood
clots were formed by recalcifying 1 ml of citrated fresh human venous blood and
then lysed by adding 1,000 units of streptokinase (SK) at several intervals
within 1 hour. Red cell deformability was tested by both a microscopic
photometric and a filtration technique, viscosity by a cone and plate viscometer,
and erythrocyte aggregation by an optical aggregometer. RESULTS: Two sampling
methods were devised for the microscopic photometric test, both of which
indicated increases of erythrocyte stiffness after being lysed from the clot by
SK. In accompanying experiments, the viscosity, aggregation and filterability of
the post-lytic erythrocytes were assessed. Results indicated increased viscosity
in Ringer's, decreased aggregation index and filterability through a 5 MUm pore
size Nuclepore membrane. CONCLUSION: Findings demonstrated that post-lytic
changes in red cell deformability do occur which could contribute to the no
reflow phenomenon.
PMID- 29332029
TI - Biomechanical effects of USS fixation with different screw insertion depths on
the vertebrae stiffness and screw stress for the treatment of the L1 fracture.
AB - OBJECTIVE: To evaluate the biomechanical effects of internal fixation with
different screw insertion depths on vertebrae stiffness and screw stress for L1
fracture. METHODS: The established L1 fracture was fixed with 10 different depths
of screw insertion: 10-100% screw-path length (SPL). Loading on the T12 endplate
was simulated. RESULTS: Screws inserted to 60-100% depths has a higher axial
displacement of screw against injured vertebrae and maximum stress of screws
compared to those of screws inserted to 30-50% depths and 10-20% (P< 0.05). No
significant difference was noted among 60-100% SPL groups. Under single loading
condition, the incidence rate of maximum stress of each screw ranged from 16.7
50.0%. Chi-square test showed superior screw has a higher incidence rate of
maximum stress than inferior screw (P< 0.05). CONCLUSIONS: Screws inserted to 60%
depth or more can achieve effective strength to withstand the postoperative
height correction loss of the L1 vertebrae fracture. However, continuous
prolonged depth of screw insertion did not significantly increase the effective
strength of the screw against injured vertebrae and maximum equivalent stress of
screws. The incidence rate of the maximum stress of each screw in correlated with
position of screw insertion but not associated with the screw insertion depth.
PMID- 29332030
TI - What is a more effective method of cranio-cervical flexion exercises?
AB - BACKGROUND: Cranio-cervical flexion exercise (CCFE) is a representative exercise
that activates the deep muscles of neck pain patients. However, there is a lack
of studies that propose specific exercise methods to examine the more effective
activity level of the deep cervical flexor. OBJECTIVE: The objective of this
study is to propose a more effective exercise method through effect comparison
based on an optimal degree of mouth-opening, a mouth-open versus mouth-closed
position, eye gaze, and body position change during CCFE. METHODS: As a result of
examining the optimal degree of mouth-opening during CCFE using a pressure
biofeedback unit with 50 subjects conforming to a selection standard,
sternocleidomastoid muscle activity was examined. An optimal degree of mouth
opening during CCFE was examined as well. In addition, muscle thickness and
muscle activity were measured based on eye gaze. Then, the effect of the exercise
based on body position was examined. RESULTS: The lowest sternocleidomastoid
activity was presented at a mouth-opening of 20 mm. A significant difference was
presented in sternocleidomastoid and longus colli muscle activity at a mouth
opening of (p< 0.05). The eye gaze of 45? below presented the lowest
sternocleidomastoid activity. CONCLUSIONS: The results suggest a new type of
exercise method with the accompaniment of an optimal degree of mouth-opening of
(20 mm), along with an eye gaze of 45? below, and an exercise method in the
seated position without spatial restriction in order to increase the effect of
CCFE, one of the conventional neck stabilization exercise methods.
PMID- 29332031
TI - Difference of the thickness and activation of trunk muscles during static stoop
lift at different loads between subjects with and without low back pain.
AB - BACKGROUND: Patients suffering from low back pain (LBP) have been reported to
alter muscle contraction strategies. OBJECTIVE: To compare activity and thickness
of the trunk muscles (external oblique (EO), internal oblique (IO), transversus
abdominis (TrA), and lumbar multifidus (LM)) during static stoop lift at
different lifting loads between the subjects with and without LBP. METHODS:
Twenty eight subjects with LBP and twenty eight healthy subjects were recruited.
The stoop lifting was performed in three conditions in 0%, 10%, and 20% of body
weight. RESULTS: The activity of EO (F= 9.513) and IO (F= 7.781) was
significantly increased with increasing lifting loads in subjects with LBP (p<
0.05) but not significantly in subjects without LBP. The activity of the LM (F=
124.980) was significantly increased in response to lifting loads in both groups
(p< 0.05). The percent change of TrA (F= 8.797) and LM (F= 48.170) muscles
thickness was significantly increased with increasing lifting loads in both
groups (p< 0.05). The percent change of TrA (F= 3.780) and LM (F= 16.314) muscles
thickness in subjects without LBP was greater than those in subjects with LBP at
all three lifting loads (p< 0.05). CONCLUSIONS: The results of this study suggest
that more activation of EO in subjects with LBP may contribute to increase the
compressive force on the lumbar spine during stoop lift. Also, less activation of
TrA and LM in subjects with LBP may contribute to decrease the lumbar
stabilization during stoop lift.
PMID- 29332032
TI - Value of conventional MRI and diffusion tensor imaging parameters in predicting
surgical outcome in patients with degenerative cervical myelopathy.
AB - BACKGROUND: In addition to conventional magnetic resonance imaging (cMRI),
diffusion tensor imaging (DTI) has been investigated as a potential diagnostic
and prognostic tool for patients with degenerative cervical myelopathy (DCM).
OBJECTIVE: To assess the efficacy of cMRI and DTI parameters in prediction of
surgical outcome in DCM patients. METHODS: One hundred and forty-two patients
with DCM who underwent presurgical cMRI and DTI of the cervical spine were
included. Quantitative parameters obtained by cMRI included compression ratio
(CR), transverse area (TA), and signal intensity ratio (SIR). DTI was evaluated
for apparent diffusion coefficient (ADC) and fractional anisotropy (FA). The
Japanese Orthopaedic Association (JOA) score and recovery rate were used to
evaluate clinical outcomes. A JOA recovery rate < 50% was defined as a poor
surgical outcome. The relationship of surgical outcome with various imaging
parameters was examined. Receiver operating characteristic (ROC) curves were used
to measure the predictive ability and determine the best cut-off values of the
quantitative parameters. RESULTS: By ROC curve analyses of imaging parameters,
the largest area under the ROC curve (AUC) was for FA (0.750), followed by ADC
(0.719), TA (0.716), SIR (0.673), and CR (0.591). The cut-off values with the
best compromise between sensitivity and specificity were set at 0.390 for FA,
1.344 * 10-3 mm2/s for ADC, 46.02 mm2 for TA, 1.556 for SIR, and 26.56% for CR.
Multivariate logistic regression model revealed that JOA score ? 8 points, TA ?
46.02 mm2, and FA ? 0.390 were independently associated with poor surgical
outcome. The AUC value for the three-predictor model was 0.871, indicating strong
predictive discrimination, and was significantly higher than the AUC value for
the model containing only the JOA score (0.763; P= 0.003). CONCLUSIONS: JOA score
is a reasonable predictor of surgical outcome in DCM. However, a model inclusive
of TA and FA provides superior predictive ability. Thus, quantitative analysis of
cMRI and DTI is useful for predicting surgical outcome in DCM.
PMID- 29332033
TI - Effect of dual tasking on anticipatory and compensatory postural adjustments in
response to external perturbations in individuals with nonspecific chronic low
back pain: Electromyographic analysis.
AB - BACKGROUND: In patients with chronic low back pain (CLBP), postural control is a
demanding task in terms of attention. Although the attentional demands of
postural control have been investigated in these patients, the attentional
demands of postural recovery during dual task performance have not been evaluated
in patients with nonspecific CLBP. OBJECTIVE: To investigate the effect of dual
tasking on anticipatory and compensatory postural adjustments in response to an
external perturbation in patients with nonspecific CLBP. METHODS: Twenty-five
patients with nonspecific CLBP of at least 3 months' duration and 25 healthy
persons were exposed to predictable and unpredictable external perturbations. The
attentional demands of postural adjustments were evaluated while participants
simultaneously performed a cognitive task. Onset latency and integrated
electromyographic activity of the trunk and leg muscles were compared between
dual task (postural recovery and backward digit span memory) and single task
conditions (postural recovery only). RESULTS: The results showed delayed
activation of the tibialis anterior (agonist) and early activation of the
gastrocnemius (antagonist) muscles during the dual task in patients with
nonspecific CLBP compared to healthy participants. Integrated electromyographic
activity was significantly greater in the dual task than the single task
condition in the gastrocnemius (antagonist) muscle in patients with nonspecific
CLBP compared to healthy persons during unpredictable perturbations. CONCLUSION:
The impaired ankle muscle activities during a cognitive task suggest that
postural control recovery following external perturbation requires attentional
resources in patients with nonspecific CLBP. This may increase the risk of re
injury in people with nonspecific CLBP while they perform an attentionally
demanding task in more difficult circumstances.
PMID- 29332034
TI - Microhemodynamic indices to evaluate the effectiveness of herbal medicine in
diabetes: A comparison between alpha-mangostin and curcumin in the retina of type
2 diabetic rats.
AB - OBJECTIVE: This study was aimed to develop microhemodynamic indices to evaluate
the effectiveness of herbal medicine in diabetic tissues. METHODS: Male Sprague
Dawley rats were divided into four groups: normal control rats (Control), type 2
diabetic rats without (DM2) and with supplementation of alpha mangostin (DM2-MG)
or curcumin (DM2-CUR). Alpha-mangostin or curcumin (200 mg/kg BW) were fed
followed by i.p. injection of streptozotocin (STZ). Mean arterial pressure (MAP)
and retinal blood flow (RBF) were measured and retinal flow resistance (RFR) was
calculated. Three indices were developed to evaluate the effectiveness of herbal
medicines in RFR-MAP diagram based on experimental data of MAP and RFR in type 2
diabetic rats. These indices are alpha, beta, and gamma where alpha is a ratio of
reduction in MAP, beta is a ratio of reduction in RFR increasing with MAP
increase, and gamma indicates a ratio of reduction in RFR. RESULTS: The elevated
MAP and RFR and decreased RBF were observed in DM2 rats.Interestingly, alpha
mangostin or curcumin supplementation significantly increased RBF while decreased
MAP and RFR. Using alpha, beta and gamma indices, it was found that alpha
mangostin is more effective than curcumin in type 2 diabetic retina. CONCLUSIONS:
These microhemodynamic indices may be useful to compare various herbal medicines
in different tissues.
PMID- 29332035
TI - An Aspartyl Cathepsin Targeted PET Agent: Application in an Alzheimer's Disease
Mouse Model.
AB - BACKGROUND: Early detection of Alzheimer's disease (AD) pathology is a serious
challenge for both diagnosis and clinical trials. The aspartyl protease,
Cathepsin D (CatD), is overexpressed in AD and could be a biomarker of disease.
We have previously designed a unique contrast agent (CA) for dual-optical and
magnetic resonance imaging of the activity of the CatD class of enzymes.
OBJECTIVE: To compare the uptake and retention of a novel, more sensitive, and
clinically-translatable 68Ga PET tracer targeting CatD activity in 5XFAD mice and
non-Tg littermates. METHODS: The targeted CA consisted of an HIV-1 Tat cell
penetrating peptide (CPP) conjugated to a specialized cleavage sequence targeting
aspartyl cathepsins and a DOTA conjugate chelating 68Ga. PET images were acquired
using a Siemens Inveon preclinical microPET in female Tg AD mice and non-Tg age
matched female littermates (n = 5-8) following intravenous CA administration at
2, 6, and 9 months of age. Additionally, 18F fluorodeoxyglucose (FDG) PET imaging
was performed at 10 months to measure glucose uptake. RESULTS: The Tg mice showed
significantly higher relative uptake rate of the targeting CA in the forebrain
relative to hindbrain at all ages compared to controls, consistent with
histology. In contrast, no differences were seen in CA uptake in other organs.
Additionally, the Tg mice did not show any differences in relative uptake of FDG
at 10 months of age in the forebrain relative to the hindbrain compared to age
matched non-Tg controls. CONCLUSIONS: Elevated aspartryl cathepsin activity was
detected in vivo in the 5XFAD mouse model of AD using a novel targeted PET
contrast agent.
PMID- 29332036
TI - Relationships Between Lower Olfaction and Brain White Matter Lesions in Elderly
Subjects with Mild Cognitive Impairment.
AB - BACKGROUND: Olfactory impairment is reported in mild cognitive impairment (MCI)
and Alzheimer's disease (AD) and is associated with hippocampal atrophy. In
elderly people, dementia with AD neuropathology and white matter lesions (WML) is
common. In this context, olfactory impairment could also depend on the presence
of WML. OBJECTIVE: To assess the cross-sectional relationship between olfaction
and WML in elderly subjects with MCI. METHODS: Consecutive subjects, >65 years
old, diagnosed as MCI after a comprehensive neuropsychological assessment in an
expert memory center, with a brain MRI performed within a year and without major
depressive state, were included. Olfaction was assessed by the Brief Smell
Identification Test (BSIT). Two trained neuroradiologists, blind to cognitive and
olfaction status, visually assessed hippocampal atrophy according to Scheltens'
scale and WML according to Fazekas criteria. RESULTS: Seventy-five MCI subjects
(mean age (SD) = 77.1 (6.2) years, 74.7% of women) were included. After
adjustment for age and sex, factors associated with low BSIT scores were older
age (p = 0.007), lower BMI (p = 0.08), lower MMSE score (p = 0.05), lower FCRST
(p = 0.008), hippocampal atrophy (p = 0.04), periventricular WML (p = 0.007), and
deep WML burden (p = 0.005). In multivariate analysis, severe deep WML (OR (95%
CI) = 6.29 (1.4-35.13), p = 0.02) remained associated with low BSIT score
independently from hippocampal atrophy. CONCLUSION: In elderly MCI subjects, low
olfactory performances are associated with WML, whose progression may be slowed
by vascular treatments. A longitudinal study to evaluate whether the progression
of WML, hippocampal atrophy and low olfactory function, can predict accurately
conversion from MCI to dementia is ongoing.
PMID- 29332038
TI - Sex Influences the Accuracy of Subjective Memory Complaint Reporting in Older
Adults.
AB - Subjective memory complaints (SMC) are required when diagnosing amnestic mild
cognitive impairment (aMCI), although their relationship with objective memory
performance and Alzheimer's disease (AD) pathology remains unclear. We
investigated whether the sex of the patient/participant moderates these
associations. Participants were 940 normal control (NC) and aMCI participants
from the Alzheimer's Disease Neuroimaging Initiative. SMC were assessed via the
memory scale of the Everyday Cognition questionnaire. Discrepancy scores were
calculated between self- and informant-reports and categorized into
"overestimates," "comparable estimates", and "underestimates" of SMC. We
conducted linear and logistic regressions to examine the interaction of sex with
self- and informant-reported SMC and discrepancy group on the Rey Auditory Verbal
Learning Test (RAVLT) Immediate and Delayed Recall and on PET measures of amyloid
beta (Abeta) positivity. Diagnosis-stratified analyses were also conducted.
Overall, there were sex by self- and informant-reported SMC interactions for
Immediate and Delayed Recall. Despite a higher proportion of "overestimates" in
women, greater self- and informant-reported SMC showed a stronger relationship to
poorer RAVLT scores in women versus men. Diagnosis-stratified analyses revealed
that results were driven by aMCI participants. Conversely, overall, greater self-
and informant-reported SMC related to greater odds of Abeta positivity regardless
of sex. In diagnosis-stratified analyses, only informant-reported SMC related to
Abeta positivity in aMCI. Relative to "comparable estimates," "underestimates" of
SMC were associated with poorer RAVLT scores across sexes in the overall sample
and in aMCI. The predictive utility of self-report SMC may be limited to women in
aMCI. Sex differences should be considered when evaluating SMC.
PMID- 29332037
TI - Increased Vulnerability of the Hippocampus in Transgenic Mice Overexpressing APP
and Triple Repeat Tau.
AB - Alzheimer's disease (AD) is the most common tauopathy, characterized by
progressive accumulation of amyloid-beta (Abeta) and hyperphosphorylated tau.
While pathology associated with the 4-repeat (4R) tau isoform is more abundant in
corticobasal degeneration and progressive supranuclear palsy, both 3R and 4R tau
isoforms accumulate in AD. Many studies have investigated interactions between
Abeta and 4R tau in double transgenic mice, but few, if any, have examined the
effects of Abeta with 3R tau. To examine this relationship, we crossed our APP751
mutant line with our recently characterized 3R tau mutant model to create a
bigenic line (hAPP-3RTau) to model AD neuropathology. Mice were analyzed at 3 and
6 months of age for pathological and behavioral endpoints. While both the 3RTau
and the hAPP-3RTau mice showed neuronal loss, increased tau aggregation, Abeta
plaques and exhibited more behavioral deficits compared to the non-tg control,
the bigenic mice often displaying relatively worsening levels. We found that even
in young animals we found that the presence of APP/Abeta increased the
accumulation of 3R tau in the neocortex and hippocampus. This observation was
accompanied by activation of GSK3 and neurodegeneration in the neocortex and CA1
region. These results suggest that in addition to 4R tau, APP/Abeta may also
enhance accumulation of 3R tau, a process which may be directly relevant to
pathogenic pathways in AD. Our results demonstrate that this bigenic model
closely parallels the pathological course of AD and may serve as a valuable model
for testing new pharmacological interventions.
PMID- 29332039
TI - Alzheimer's Disease rs11767557 Variant Regulates EPHA1 Gene Expression
Specifically in Human Whole Blood.
AB - Large-scale genome-wide association studies have reported EPHA1 rs11767557
variant to be associated with Alzheimer's disease (AD) risk in the European
population. However, it is still unclear how this variant functionally
contributes to the underlying disease pathogenesis. The rs11767557 variant is
located approximately 3 kb upstream of EPHA1 gene. We think that rs11767557 may
modify the expression of nearby genes such as EPHA1 and further cause AD risk.
Until now, the potential association between rs11767557 and the expression of
nearby genes has not been reported in previous studies. Here, we evaluate the
potential expression association between rs11767557 and EPHA1 using multiple
large-scale eQTLs datasets in human brain tissues and the whole blood. The
results show that rs11767557 variant could significantly regulate EPHA1 gene
expression specifically in human whole blood. These findings may further provide
important supplementary information about the regulating mechanisms of rs11767557
variant in AD risk.
PMID- 29332040
TI - Synthetic Fragment of Receptor for Advanced Glycation End Products Prevents
Memory Loss and Protects Brain Neurons in Olfactory Bulbectomized Mice.
AB - Activation of receptor for advanced glycation end products (RAGE) plays an
essential role in the development of Alzheimer's disease (AD). It is known that
the soluble isoform of the receptor binds to ligands and prevents negative
effects of the receptor activation. We proposed that peptide fragments from RAGE
prevent negative effects of the receptor activation during AD neurodegeneration.
We have synthesized peptide fragments from surface-exposed regions of RAGE.
Peptides were intranasally administrated into olfactory bulbectomized (OBX) mice,
which developed some characteristics similar to AD neurodegeneration. We have
found that only insertion of fragment (60-76) prevents the memory of OBX mice.
Immunization of OBX mice with peptides showed that again only (60-76) peptide
protected the memory of animals. Both intranasal insertion and immunization
decreased the amyloid-beta (Abeta) level in the brain. Activity of shortened
fragments of (60-76) peptide was tested and showed only the (60-70) peptide is
responsible for manifestation of activity. Intranasal administration of (60-76)
peptide shows most protective effect on morpho-functional characteristics of
neurons in the cortex and hippocampal areas. Using Flu-(60-76) peptide, we
revealed its penetration in the brain of OBX mice as well as colocalization of
Flu-labeled peptide with Abeta in the brain regions in transgenic mice. Flu-(60
76) peptide complex with trimer of Abeta was detected by SDS-PAGE. These data
indicate that Abeta can be one of the molecular target of (60-70) peptide. These
findings provide a new peptide molecule for design of anti-AD drug and for
investigation of RAGE activation ways in progression of AD neurodegeneration.
PMID- 29332041
TI - In Vivo Visualization of Tau Accumulation, Microglial Activation, and Brain
Atrophy in a Mouse Model of Tauopathy rTg4510.
AB - BACKGROUND: Tau imaging using PET is a promising tool for the diagnosis and
evaluation of tau-related neurodegenerative disorders, but the relationship among
PET-detectable tau, neuroinflammation, and neurodegeneration is not yet fully
understood. OBJECTIVE: We aimed to elucidate sequential changes in tau
accumulation, neuroinflammation, and brain atrophy by PET and MRI in a tauopathy
mouse model. METHODS: rTg4510 transgenic (tg) mice expressing P301L mutated tau
and non-tg mice were examined with brain MRI and PET imaging (analyzed numbers:
tg = 17, non-tg = 13; age 2.5~14 months). As PET probes, [11C]PBB3 (Pyridinyl
Butadienyl-Benzothiazole 3) and [11C]AC-5216 were used to visualize tau pathology
and 18-kDa translocator protein (TSPO) neuroinflammation. Tau pathology and
microglia activation were subsequently analyzed by histochemistry. RESULTS: PET
studies revealed age-dependent increases in [11C]PBB3 and [11C]AC-5216 signals,
which were correlated with age-dependent volume reduction in the forebrain on
MRI. However, the increase in [11C]PBB3 signals reached a plateau at age 7
months, and therefore its significant correlation with [11C]AC-5216 disappeared
after age 7 months. In contrast, [11C]AC-5216 showed a strong correlation with
both age and volume reduction until age 14 months. Histochemical analyses
confirmed the relevance of pathological tau accumulation and elevated TSPO
immunoreactivity in putative microglia. CONCLUSION: Our results showed that tau
accumulation is associated with neuroinflammation and brain atrophy in a
tauopathy mouse model. The time-course of the [11C]PBB3- and TSPO-PET finding
suggests that tau deposition triggers progressive neuroinflammation, and the
sequential changes can be evaluated in vivo in mouse brains.
PMID- 29332043
TI - Serum Non-Ceruloplasmin Non-Albumin Copper Elevation in Mild Cognitive Impairment
and Dementia due to Alzheimer's Disease: A Case Control Study.
AB - Several studies showed high serum copper levels in Alzheimer's disease (AD). The
present study applied a newly developed method to detect serum copper free from
proteins (free-Cu). Forty-four patients affected by dementia due to AD, thirty
six patients affected by mild cognitive impairment (MCI) due to AD, and twenty
eight healthy controls underwent clinical, cognitive, and MRI assessment. The new
method showed higher free-Cu concentrations in MCI and dementia due to AD
compared to controls (p < 0.0001). No correlation between copper levels,
cognitive or MRI measures were found.
PMID- 29332044
TI - Does the Genetic Feature of the Chinese Tree Shrew (Tupaia belangeri chinensis)
Support Its Potential as a Viable Model for Alzheimer's Disease Research?
AB - Alzheimer's disease (AD) is a neurodegenerative disease with increasing incidence
across the world and no cure at the present time. An ideal animal model would
facilitate the understanding of the pathogenesis of AD and discovery of potential
therapeutic targets. The Chinese tree shrew (Tupaia belangeri chinensis) has a
closer genetic affinity to primates relative to rodents, and can attain ages of 8
years or older, which represents another advantage for the study of
neurodegenerative diseases such as AD compared to primates. Here, we analyzed 131
AD-related genes in the Chinese tree shrew brain tissues based on protein
sequence identity, positive selection, mRNA, and protein expression by comparing
with those of human, rhesus monkey, and mouse. In particular, we focused on the
Abeta and neurofibrillary tangles formation pathways, which are crucial to AD
pathogenesis. The Chinese tree shrew had a generally higher sequence identity
with human than that of mouse versus human for the AD pathway genes. There was no
apparent selection on the tree shrew lineage for the AD-related genes. Moreover,
expression pattern of the Abeta and neurofibrillary tangle formation pathway
genes in tree shrew brain tissues resembled that of human brain tissues, with a
similar aging-dependent effect. Our results provided an essential genetic basis
for future AD research using the tree shrew as a viable model.
PMID- 29332045
TI - The Uniform Data Set, Czech Version: Normative Data in Older Adults from an
International Perspective.
AB - BACKGROUND: Outside of the United States, international perspectives on normative
data for neuropsychological test performance, within diverse populations, have
been scarce. The neuropsychological test battery from the Uniform Data Set (UDS)
of the Alzheimer's Disease Centers (ADC) program of the United States National
Institute on Aging (NIA) is one of the most sensitive batteries for the
evaluation of both normal cognitive aging and pathological cognitive decline.
OBJECTIVE: This study aimed to determine the feasibility of the Czech
Neuropsychological Test Battery from the Uniform Data Set (UDS-Cz 2.0), while
also evaluating the results obtained from an international perspective. METHODS:
This paper describes data from 520 cognitively normal participants. Regression
analyses were used to describe the influence of demographic variables on UDS-Cz
test performance. RESULTS: Cognitive performance on all measures declined with
age, with patient education level serving as a protective factor. Therefore, the
present study provides normative data for the UDS-Cz, adjusted for the
demographic variables of age and education. CONCLUSION: The present study
determines the psychometric properties of the UDS-Cz and establishes normative
values in the aging Czech population, which can be used in clinical settings.
PMID- 29332046
TI - A Novel Antibody Targeting Tau Phosphorylated at Serine 235 Detects
Neurofibrillary Tangles.
AB - Alzheimer's disease is characterized by two main pathological hallmarks in the
human brain: the extracellular deposition of amyloid-beta as plaques and the
intracellular accumulation of the hyperphosphorylated protein tau as
neurofibrillary tangles (NFTs). Phosphorylated tau (p-tau) specific-antibodies
and silver staining have been used to reveal three morphological stages of NFT
formation: pre-NFTs, intraneuronal NFTs (iNFTs), and extraneuronal NFTs (eNFTs).
Here we characterize a novel monoclonal antibody, RN235, which is specific for
tau phosphorylated at serine 235, and detects iNFTs and eNFTs in brain tissue,
suggesting that phosphorylation at this site is indicative of late stage changes
in tau.
PMID- 29332042
TI - Protective Effects of Indian Spice Curcumin Against Amyloid-beta in Alzheimer's
Disease.
AB - The purpose of our article is to assess the current understanding of Indian
spice, curcumin, against amyloid-beta (Abeta)-induced toxicity in Alzheimer's
disease (AD) pathogenesis. Natural products, such as ginger, curcumin, and gingko
biloba have been used as diets and dietary supplements to treat human diseases,
including cancer, cardiovascular, respiratory, infectious, diabetes, obesity,
metabolic syndromes, and neurological disorders. Products derived from plants are
known to have protective effects, including anti-inflammatory, antioxidant, anti
arthritis, pro-healing, and boosting memory cognitive functions. In the last
decade, several groups have designed and synthesized curcumin and its derivatives
and extensively tested using cell and mouse models of AD. Recent research on
Abeta and curcumin has revealed that curcumin prevents Abeta aggregation and
crosses the blood-brain barrier, reach brain cells, and protect neurons from
various toxic insults of aging and Abeta in humans. Recent research has also
reported that curcumin ameliorates cognitive decline and improves synaptic
functions in mouse models of AD. Further, recent groups have initiated studies on
elderly individuals and patients with AD and the outcome of these studies is
currently being assessed. This article highlights the beneficial effects of
curcumin on AD. This article also critically assesses the current limitations of
curcumin's bioavailability and urgent need for new formulations to increase its
brain levels to treat patients with AD.
PMID- 29332047
TI - Sally-Anne Test in Patients with Alzheimer's Disease Dementia.
AB - Social cognition has recently been recognized as one of the essential cognitive
domains. Some reports suggested that patients with Alzheimer's disease dementia
(ADD) presented significant theory of mind deficits even in the mild condition.
However, most previous studies included only small numbers of patients with ADD.
The present study administered the first-order false belief (Sally-Anne) test to
116 consecutive patients with ADD from the outpatient units of the Memory Clinic
and compared the characteristics of the two groups with correct and incorrect
answers on the test. Then various clinical characteristics were evaluated. Only
37.1% of patients with ADD correctly answered the Sally-Anne test with the right
explanation. Comparison between the two groups of correct and incorrect answers
revealed a significant association between the frontal assessment battery score
and the result of the Sally-Anne test in the multiple logistic regression
analyses. Thus, patients with ADD presented a significant deficit in social
cognition even in the mild condition. Frontal dysfunction was thought to be
related to the deficits in mild ADD.
PMID- 29332048
TI - Frequency of Cardiovascular Genetic Risk Factors in a Calabrian Population and
Their Effects on Dementia.
AB - BACKGROUND: Several genetic variants playing a key role in cholesterol levels,
blood pressure, and vascular dysfunction influence the risk of Alzheimer's
disease (AD) and vascular dementia (VaD). The many meta-analysis studies carried
out on large numbers of samples in different populations have not provided clear
results to date, because a trans-ethnic shift of risk genotypes in different
populations is often observed. OBJECTIVES: To determine genotypes allele
frequencies of the polymorphisms most frequently identified to be correlated with
cardio-cerebrovascular disease and AD in a Southern Italy population and to
investigate their possible association with dementia. METHODS: The genotype and
allele frequencies of 13 cardio-cerebrovascular risk polymorphisms were assessed
and their possible association with dementia was investigated in a case-control
study, including 221 consecutive unrelated subjects diagnosed with dementia (120
subjects affected by AD, 55 by frontotemporal dementia, and 33 by vascular
dementia) and 218 matched controls of Calabrian origin. RESULTS: Carriers of at
least one APOEE4 allele resulted to be at higher risk of AD [OR(95% CI) =
2.721(1.477-5.011)] and VaD [OR(95% CI) = 6.205(2.356-16.342)] compared to non
carriers. Individuals with the IV genotype of the CETP polymorphism were more
likely to have AD [OR(95% CI) = 2.427(1.364-4.319)] and VaD [OR(95% CI) =
3.649(1.455-9.152)] compared to subjects with the II-VV genotypes. CONCLUSION:
CETP I405V polymorphism is likely a risk factor for AD and VaD in our cohort,
independent of APOEE4 status. Unmodifiable genetic risk factors should be taken
into account to promote a healthy lifestyle to prevent dementia.
PMID- 29332049
TI - Free Heme and Amyloid-beta: A Fatal Liaison in Alzheimer's Disease.
AB - While the etiology of Alzheimer's disease (AD) is still unknown, an increased
formation of amyloid-beta (Abeta) peptide and oxidative processes are major
pathological mechanism of the disease. The interaction of Abeta with free heme
leads to the formation of peroxidase-active Abeta-heme complexes. However, enzyme
kinetic data and systematic mutational studies are still missing. These aspects
were addressed in this study to evaluate the role of Abeta-heme complexes in AD.
The enzyme-kinetic measurements showed peroxidase-specific pH- and H2O2
dependencies. In addition, the enzymatic activity of Abeta-heme complexes
constantly increased at higher peptide excess. Moreover, the role of the Abeta
sequence for the named enzymatic activity was tested, depicting human-specific
R5, Y10, and H13 as essential amino acids. Also by studying Y10 as an endogenous
peroxidase substrate for Abeta-heme complexes, ratio-specific effects were
observed, showing an optimal dityrosine formation at an about 40-fold peptide
excess. As dityrosine formation promotes Abeta fibrillation while free heme
disturbs protein aggregation, we also investigated the effect of Abeta-heme
complex-derived peroxidase activity on the formation of Abeta fibrils. The
fluorescence measurements showed a different fibrillation behavior at strong
peroxidase activity, leading also to altered fibril morphologies. The latter was
detected by electron microscopy. As illustrated by selected in vivo measurements
on a mouse model of AD, the disease is also characterized by Abeta-derived
microvessel destructions and hemolytic processes. Thus, thrombo-hemorrhagic
events are discussed as a source for free heme in brain tissue. In summary, we
suggest the formation and enzymatic activity of Abeta-heme complexes as
pathological key features of AD.
PMID- 29332050
TI - Supplemental Retinal Carotenoids Enhance Memory in Healthy Individuals with Low
Levels of Macular Pigment in A Randomized, Double-Blind, Placebo-Controlled
Clinical Trial.
AB - BACKGROUND: There is a biologically plausible rationale whereby the dietary
carotenoids lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ), which are
collectively referred to as macular pigment (MP) in the central retina (macula),
support the maintenance of cognition via their antioxidant and anti-inflammatory
properties. OBJECTIVE: To investigate the impact of supplemental L, Z, and MZ on
memory, executive function, and verbal fluency among healthy individuals with low
MP levels. METHODS: In this double-blind, placebo-controlled, randomized clinical
trial, subjects (n = 91; mean+/-SD age = 45.42+/-12.40; % male = 51.6) consumed a
daily formulation of 10 mg L, 10 mg MZ, and 2 mg Z (n = 45) or placebo (n = 46)
for 12 months. Cognitive domains assessed included verbal and visual learning,
immediate and delayed memory, executive function, and verbal fluency. MP and
serum carotenoid concentrations of L, Z, and MZ were also measured. RESULTS:
Following 12-month supplementation, individuals in the active group exhibited
statistically significant improvements in memory when compared to the placebo
group (paired associated learning [PAL] memory score [rANOVA, p = 0.009]; PAL
errors [rANOVA, p = 0.017]). Furthermore, the observed reduction in the number of
errors made in the PAL task among those in the intervention group was positively
and significantly related to observed increases in MP volume (p = 0.005) and
observed increases in serum concentrations of L (p = 0.009). CONCLUSION: This
randomized, double-blind, placebo-controlled clinical trial demonstrates a memory
enhancing effect of daily supplementation with L, Z, and MZ in healthy subjects
with low MP at baseline. The implications of these findings for intellectual
performance throughout life, and for risk of cognitive decline in later life,
warrant further study.
PMID- 29332051
TI - The Impact of Music on the Self in Dementia.
AB - In this review, we consider how the onset and progression of dementia can disrupt
one's sense of self, and propose that music is an ideal tool for alleviating this
distressing symptom. Various aspects of the self can be impaired in people with
dementia, depending on how the self is defined. There are anecdotal reports that
music can 'bring people back to themselves' in the face of dementia, but there
have been scarce empirical investigations of this topic. Motivated by a
consideration of the existing literature, we outline a novel theoretical
framework that accounts for the relationship between music and the self in people
with dementia. We propose that music has a number of 'design features' that make
it uniquely equipped to engage multiple aspects of the self. We suggest that each
design feature interacts with different aspects of the self to varying degrees,
promoting overall wellbeing. We discuss how existing research on music and
dementia fits within this framework, and describe two case studies in which music
was an ideal stimulus for reaffirming their sense of self. Our framework may be
useful for the diagnosis and treatment of impairments of self in people with
dementia, and highlights how music, given its ability to engage all aspects of
the self simultaneously, can result in an overall enhanced sense of self.
PMID- 29332052
TI - When Art Meets Gardens: Does It Enhance the Benefits? The Nancy Hypothesis of
Care for Persons with Alzheimer's Disease.
AB - The creation of healing gardens for persons with Alzheimer's disease and related
diseases (ADRD) offers vast potential. They can play a role in the scaffolding of
cognitive disorders, emotional stress, sensory processing, sense of harmony, and
appeasement. These effects are achieved through a distributed interplay of
psychological functions with the immediate environment and local culture on the
one hand, and dialogue on the other. The garden, a natural canvas created by man,
shares with art the ability to foster an esthetic sense for which the perception
can be measured by functional neurological imaging exploration. Art represents a
mediator for the collaborative realization of distributed psychological functions
between different individuals. Based on the hypothesis of an optimization of the
therapeutic potential of a garden by a design adapted to the neuro-psycho-social
and cultural specificities of its users combined with the thoughtful introduction
of an artistic dimension, the "art, memory and life" healing garden was created
at the University Hospital of Nancy as a prototype for persons with ADRD. The
design concept was based on two hypotheses that we formulate herein, discuss
their theoretical foundation, and suggest enhanced design for therapeutic gardens
based upon our experience.
PMID- 29332053
TI - Apparent Cognitive Decline as Revealed by an Executive Function Test within a
Cohort of Elderly Individuals Self-Reporting Normal Cognitive Performance.
AB - Alzheimer's disease (AD) can be preceded by subtle memory decline that can last a
decade or more before progressing to what would be diagnosed as the mild
cognitive impairment stage. During this early stage of decline, individuals and
even their caregivers can fail to perceive any serious difficulty or need to
consult a physician. Herein, we present evidence in support of these concerns,
and demonstrate how this can interfere not only with clinical trials of AD but
also those involving cognitive performance of elderly individuals without
intentional reference to AD.
PMID- 29332054
TI - Dementia and Atrial Fibrillation: A Dangerous Combination for Ischemic Stroke and
Mortality.
AB - The risk of developing dementia is increased in patients with atrial fibrillation
(AF), with the incidence of both conditions increasing with aging. Patients with
dementia frequently do not receiving adequate thrombo-prophylaxis, because of the
inability to monitor INR and/or to achieve and maintain good compliance with
anticoagulant treatment. Under-treatment is therefore an important contributor to
the increased risk of ischemic stroke and mortality in this subgroup of AF
patients. In newly-diagnosed patients with AF starting oral anticoagulation, the
presence of cognitive impairment should be considered in addition to the
calculation of the SAMe-TT2R2 score, as part of an integrated decision management
pathway to choose the most appropriate oral anticoagulant [i.e., vitamin K
antagonists (VKAs) or non-vitamin K oral anticoagulants (NOACs)]. Moreover, in
patients with low or worsening time in therapeutic range during VKAs therapy, the
assessment of cognitive impairment may help identify those patients who may
benefit from switching to NOACs. In conclusion, patients with AF and dementia
benefit from anticoagulation and should not be denied receiving adequate stroke
prevention. Cognitive function assessment and social support are pivotal elements
in the management of these AF patients.
PMID- 29332055
TI - Operating room scheduling and surgeon assignment problem under surgery durations
uncertainty.
AB - BACKGROUND: Scientific management methods are urgently needed to balance the
demand and supply of heath care services in Chinese hospitals. Operating theatre
is the bottleneck and costliest department. Therefore, the surgery scheduling is
crucial to hospital management. OBJECTIVE: To increase the utilization and reduce
the cost of operating theatre, and to improve surgeons' satisfaction in the
meantime, a practical surgery scheduling which could assign the operating room
(OR) and surgeon for the surgery and sequence surgeries in each OR was provided
for hospital managers. METHODS: Surgery durations were predicted by fitting the
distributions. A two-step mixed integer programming model considering surgery
duration uncertainty was proposed, and sample average approximation (SAA) method
was applied to solve the model. RESULTS: Durations of various surgeries were log
normal distributed respectively. Numerical experiments showed the model and
method could get good solutions with different sample sizes. CONCLUSIONS: Real
life constraints and duration uncertainty were considered in the study, and the
model was also very applicable in practice. Average overtime of each OR was
reducing and tending to be stable with the number of surgeons increasing, which
is a discipline for OR management.
PMID- 29332056
TI - Ozone injection with or without percutaneous microdiscectomy for treatment of
cervical disc herniation.
AB - OBJECTIVE: This retrospective study compared the efficacy of combined
percutaneous ozone injection and percutaneous discectomyto percutaneous ozone
injection alone for the treatment of cervical disc herniation. METHODS: Patients
with cervical disc herniation who were enrolled in our hospital from October 2010
to June 2015 were divided into two groups: 1) treated with percutaneous ozone
injection alone (control; n= 19); and 2) those treated with combined ozone
injection and percutaneous microdiscectomy (combined treatment; n= 28). The
efficacy of the combined treatment was evaluated relative to the control by
visual analogue scale (VAS) and the modified Macnab standard. Effective treatment
was defined as excellent or good, and ineffective as fair or poor. RESULTS: No
major complications occurred in either group. For the control group, the VAS
scores dropped from 6.75 +/- 2.34 before surgery to 2.78 +/- 1.85 immediately
after surgery, and to 4.18 +/- 1.46 during the follow-ups. For patients who
received the combined treatment, the VAS scores were 7.12 +/- 2.03 before
surgery, 3.86 +/- 2.87 immediately after surgery, and 3.27 +/- 1.53 during the
follow-ups. At the 6-month follow-up, 73.7% (14 from 19 patients) in the control
group and 89.2% (25 from 28 patients) in the treatment group were judged to have
received effective treatment. Difference in efficacy between two groups of
treatment was statistically significant (P= 0.033). CONCLUSION: The rate of
effective treatment in patients who received combined percutaneous
microdiscectomy and ozone injection was higher than that of patients who received
ozone injection alone. Combination of percutaneous microdiscectomy and ozone
injection might be an effective method to treat patients with cervical disk
hernia.
PMID- 29332057
TI - Evaluation of thickness of CAD/CAM fabricated zirconia cores by digital
microscope.
AB - Despite several advantages of digitalized workflow, researchers have noted
discrepancies in the precision and trueness. This study investigated the accuracy
in the final thickness of Zirconia (Zr) cores fabricated by five CAD/CAM systems.
Standardized manufacturing of the cores with 1 mm thickness were carried out.
Cores were then sectioned into two halves and measurement made with Digital
Microscope at 5 points in micrometers. Overall, mean thickness for the groups was
1048.81 +/- 94.01, which was 48 MUm higher than the thickness programmed in the
software. Anova showed a statistically significant difference between the groups
(p= 0.000). Presence of variations in the thickness and 5 measurement points for
the CAD/CAM systems investigated was found. No significant difference was
observed and the thickness of the cores were within acceptable level.
PMID- 29332058
TI - 3D surface-imaging for volumetric measurement in people with obesity.
AB - BACKGROUND: Current methods for tracking the progress of people with obesity
towards a weight loss goal appear simple and potentially misleading. A technique
to quantify change in body shape whilst visualising areas of the body where
weight loss occurs would be advantageous, and has the potential to be used as a
motivational tool. Three-dimensional (3D) surface-imaging would serve as a good
basis for such a technique, however current systems are prohibitively expensive.
OBJECTIVE: Highlight the use of a cheaper alternative 3D surface-imaging system
for volumetric measurement in people with obesity. METHODS: A recently developed
low-cost 3D surface-imaging system was used, having previously being validated in
a healthy population. A total of 61 people with obesity, enrolled on a weight
loss programme, were surface-imaged using the system. RESULTS: The findings
suggest the low-cost system can obtain 3D surface-images of an obese human body,
from which numerical parameters could be calculated and further analysis
conducted. CONCLUSIONS: Further studies will focus on the validity and
reliability of such analyses and the potential of the system to be considered as
a long-term instalment in primary healthcare settings as a weight loss aid.
PMID- 29332059
TI - Analysis of skeletal muscle performance using piezoelectric film sensors.
AB - A flexible piezoelectric thin film sensor has been proposed recently in several
studies for detection of muscle movements. The objective of this study was to
investigate the ability of this sensor to assess skeletal muscle performance and
fatigue under isokinetic contractions. Simultaneous noninvasive measurements of
muscles activity were done using surface electromyography (EMG) electrodes and
two thin film piezoelectric sensors. Measurements were taken from the biceps
during slow and fast elbow flexion with and without strong grip, during different
weight lifting and from the gastrocnemius during treadmill marching at speeds of
4 and of 10 kph. The results shows correlation between the onset of EMG and the
piezoelectric sensors (Piezo) signals during muscle contraction. Increasing
contraction intensity increase significantly both EMG and Piezo signals. Higher
contractions velocity increased Piezo signal. Opposite linear relation was found
between the average maximal EMG envelope amplitudes and the average maximal Piezo
peaks with increasing loads. The significant decrease in the maximal Piezo peaks
with time of all 3 subjects during elbow flexion while holding weight suggests
the ability of piezoelectric thin film sensor to track muscle fatigue during
isokinetic contractions.
PMID- 29332060
TI - Information technology as a tool for the Italian Institute of Social Security
(INPS) in the management of social security and civil disability: Pro and cons.
AB - We examine, from a medical-legal perspective, the pro and cons of the information
technology procedures that the Italian Institute of Social Security (INPS) has
implemented to manage the provision of social disability assistance, meaning that
separate from the payment of pension contributions, being welfare, anchored to an
administrative requirement by way of the compulsory payment of a minimum social
security contribution.
PMID- 29332061
TI - Design and implementation of an advanced telemedicine model for the rural people
of Bangladesh.
AB - OBJECTIVES: Telemedicine based healthcare service faces different difficulties
especially in the remote people of Bangladesh. The objective of this study was to
implement an advanced telemedicine model in order to provide the healthcare
services for the rural people of Bangladesh. METHODS: We developed the
telemedicine model using an ardunio based low cost portable telemedicine tool kit
by interfacing android application. Then we collected ECG, blood pressure,
temperature, concentration of glucose in blood, SPO2, body position, airflow,
height and weight through our developed model. Moreover, we designed a server for
storing the recorded signal from the patients in order to treat them by health
care professionals. Finally, this model is successfully tested with the patients
of Marie Stopes Bangladesh Hospital Dhaka. RESULTS: We have removed noise from
the recorded signal successfully through our developed hardware and software
based techniques. Real time data were visualized to the expert doctor in order to
prescribe them through our model. CONCLUSIONS: These results support that rural
patient vital information can be collected in an automated way through the
advanced model. Both rural and urban doctors can share and exchange patient
information more effectively for the treatment of patient. The results of this
research indicated that our developed telemedicine system can be used effectively
in order to deliver healthcare services for the rural people of Bangladesh.
PMID- 29332062
TI - Cytologic Features of Malignant Melanoma with Osteoclast-Like Giant Cells.
AB - BACKGROUND: Malignant melanoma showing numerous osteoclast-like giant cells
(OGCs) is an uncommon morphologic phenomenon, rarely mentioned in the cytologic
literature. The few reported cases seem to have an aggressive clinical behavior.
Although most findings support monocyte/macrophage differentiation, the exact
nature of OGCs is not clear. CASE: A 57-year-old woman presented with an inguinal
lymphadenopathy. Sixteen years before, cutaneous malignant melanoma of the lower
limb had been excised. Needle aspiration revealed abundant neoplastic single
cells as well as numerous multinucleated OGCs. Occasional neoplastic giant cells
were also present. Nuclei of OGCs were monomorphic with oval morphology and were
smaller than those of melanoma cells. The immunophenotype of OGCs (S100-, HMB45-,
Melan-A-, SOX10-, Ki67-, CD163-, BRAF-, CD68+, MiTF+, p16+) was the expected for
reactive OGCs of monocyte/macrophage origin. The tumor has shown an aggressive
behavior with further metastases to the axillary lymph nodes and oral cavity.
CONCLUSION: Numerous OGCs are a rare and relevant finding in malignant melanoma.
Their presence should not induce confusion with other tumors rich in osteoclastic
cells. Since a relevant number of OGCs in melanoma may mean a more aggressive
behavior, and patients may benefit from specific treatments, their presence
should be mentioned in the pathologic report.
PMID- 29332063
TI - Diffusion Tensor Imaging Investigation of Uncinate Fasciculus Anatomy in Healthy
Controls: Description of a Subgenual Stem.
AB - The uncinate fasciculus is the largest white matter association tract connecting
the prefrontal cortex and the anteromedial temporal lobe. The traditional
anatomical description outlines a temporal stem that hooks around the posterior
insula, a subinsular body, and 2 prefrontal stems extending to the lateral
orbital gyri and the frontopolar cortex. Recent imaging studies of the white
matter tracts deep to the subgenual cingulate gyrus (Brodmann area 25: BA25)
suggest the presence of white matter fibers extending from BA25 to the amygdala,
via a route that would run in close proximity to the uncinate fasciculus, that
are of functional importance in mood disorders. We hypothesized that these fibers
represent a third, medial prefrontal stem of the uncinate fasciculus. Using
diffusion tensor imaging in 74 healthy volunteer humans, we seeded the uncinate
fasciculus using 2 regions of interest centered over the temporal stem and the
caudal body of the uncinate fasciculus in the coronal plane at the level of the
anterior commissure. A medial prefrontal stem extending to the subgenual
cingulate gyrus was demonstrated in 65/74 left and 70/74 right cerebral
hemispheres, and had a mean fractional anisotropy value of 0.43 (95% CI 0.40
0.47). The medial subgenual stem fibers were inseparable from the caudal body and
temporal stem of the main uncinate fasciculus and followed the same hook-shaped
morphology. A probable medial subgenual prefrontal stem of the uncinate
fasciculus was demonstrated in a cohort of healthy volunteers and is of potential
significance in our understanding of neuropsychiatry and mood disorders.
PMID- 29332064
TI - Recurrent Intragenic Duplication within the NR5A1 Gene and Severe Proximal
Hypospadias.
AB - A heterozygous intragenic duplication within the repeated area (CTGCAGCTG)*2 of
the NR5A1 gene was found in a 15-year-old 46,XY DSD (disorders/differences of sex
development) patient with micropenis and severe proximal hypospadias. This
heterozygous duplication has already been described twice in boys with a similar
phenotype, whereas a deletion of 3 amino acids at the same position in the
protein SF-1 has been described in a 46,XX patient with primary ovarian failure
and short stature. These data suggest that this region within the NR5A1 gene has
an important role for SF-1 protein function in gonads and is a hotspot for
intragenic rearrangements.
PMID- 29332065
TI - A Novel Mutation of AMHR2 In Two Siblings with Persistent Mullerian Duct
Syndrome.
AB - Persistent mullerian duct syndrome (PMDS) is characterized by the presence of
mullerian duct derivatives in otherwise phenotypically normal males. It is caused
in approximately 85% of the cases by mutations in the AMH gene or its type II
receptor (AMHR2). We report on 2 brothers with normal external genitalia but high
serum AMH levels. Sequence analysis of the AMHR2 gene in the 2 siblings revealed
a novel homozygous missense mutation in exon 10 (p.V458L, c.1372G>T). PMDS is a
rare condition, but it has to be considered in differential diagnosis of
cryptorchidism with normal male genitalia.
PMID- 29332066
TI - Correlation between Serum Calcineurin Activity and Left Ventricular Hypertrophy
in Hypertensive Patients and Its Clinical Significance.
AB - OBJECTIVE: The aim of this study is to investigate the correlation between
calcineurin (CaN) and hypertension with left ventricular hypertrophy (HLVH) and
to evaluate its potential clinical significance. DESIGN: The study involved 160
patients diagnosed with hypertension and 42 controls. Based on the exclusion
criteria, 42 were not eligible for this study. The remaining 118 hypertensive
patients were categorized into 2 subgroups based on left ventricular mass index
and relative ventricular wall thickness: a normal model subgroup with
hypertension (HNM) and an HLVH subgroup. Serum CaN levels were determined by
enzyme-linked immunosorbent assay, while serum CaN activity was determined by
malachite green colorimetric assay. RESULTS: Among the HNM and HLVH subgroups, a
positive correlation was demonstrated between serum CaN activity, but not serum
CaN level, and HLVH. Moreover, the HLVH subgroup displayed a remarkable increase
in the levels of brain natriuretic peptide, cystatin C, urinary
albumin/creatinine ratio, and left atrium diameter compared to the HNM subgroup
and controls. CONCLUSION: There was a positive correlation between serum CaN
activity and LVH in hypertensive patients. Activated CaN could play an important
role in the pathophysiologic mechanism of HLVH. Serum CaN activity could be a
clinically useful diagnostic and prognostic biomarker for LVH.
PMID- 29332067
TI - Incidence of and Risk Factors for Residual Anastomoses in Twin-Twin Transfusion
Syndrome Treated with Laser Surgery: A 15-Year Single-Center Experience.
AB - OBJECTIVES: To evaluate the incidence of residual anastomoses (RA) after laser
therapy for twin-twin transfusion syndrome (TTS) and investigate risk factors for
incomplete laser surgery. MATERIAL AND METHODS: All available TTS placentas
treated with laser at our center between 2002 and 2016 were injected with color
dye to assess the presence of RA. We evaluated the incidence of RA over the past
15 years by dividing the cohort into three time periods, and studied the
association with risk factors and neonatal outcome. RESULTS: Overall, RA were
detected in 21.0% (78/371) of placentas. The incidence of RA decreased from 38.8%
(26/67) in the initial period to 11.7% (16/137) in the most recent period (p <
0.001). On multivariate analysis, several risk factors were independently
associated with the risk of RA, including Solomon laser technique (odds ratio
[OR] 0.17, 95% CI 0.09-0.33) and estimation of surgical success (OR 19.28, 95% CI
8.17-45.49). Premature delivery and neonatal morbidity occurred more often in TTS
cases with RA. CONCLUSIONS: The incidence of RA after laser therapy for TTS
decreased significantly in the past 15 years and is now below 15% due to the use
of the Solomon technique.
PMID- 29332068
TI - The Role of Preoperative Steroids for Hearing Preservation Cochlear Implantation:
Results of a Randomized Controlled Trial.
AB - OBJECTIVES: To determine whether preoperative steroids can improve hearing
outcomes in cochlear implantation (CI). METHODS: This is a randomized controlled
trial involving 30 postlingual deaf CI patients. Subjects had preoperative
thresholds of better than or equal to 80 dB at 125 and 250 Hz, and better than or
equal to 90 dB at 500 and 1,000 Hz. The subjects were randomized to a control
group, an oral steroid group (receiving 1 mg/kg/day of prednisolone for 6 days
prior to surgery), or a transtympanic steroid group (receiving a single dose of
0.5 mL of 10 mg/mL dexamethasone at 24 h prior to surgery). RESULTS: The subjects
receiving transtympanic steroids had a significant decrease in the pure tone
average over 3 months compared to the control and oral steroid group, which
persisted over 12 months (p < 0.05). CONCLUSION: A single dose of preoperative
transtympanic steroids prior to CI appears to have a beneficial effect, at least
in the short term, with minimal effects seen in the longer term.
PMID- 29332069
TI - The History of Movement Disorder Brain Surgery.
AB - The first surgical procedures for abnormal movement disorders began in the 1930s,
when surgeons first proposed ablative techniques of the caudate nucleus or
transection of motor (pyramidal) pathways to reduce involuntary movements in
patients with Parkinson's related tremor. During the 50-year interval between
1945 and 1995, the development of precise intracranial guiding devices, brain
maps, and advanced imaging led to the refinement of appropriate deep brain
targets affecting extrapyramidal pathways. Lesional surgery and subsequent
neuroaugmentation using deep brain stimulation extended the role of deep brain
surgery for a wider group of patients with tremor, rigidity, dyskinesia, and
other involuntary movement disorders. Stereotactic radiosurgery has had wide
application for tremor. The history of movement disorder surgery reads like a
who's who of brilliant and resourceful surgeons who pushed the frontiers of
neurosurgery. Even today, practitioners of functional brain surgery are among the
most innovative practicing neurosurgeons.
PMID- 29332070
TI - Pathophysiologic Basis of Movement Disorders.
AB - Movement disorders are common and functionally disabling neurologic diseases.
Studies over the last decades have investigated the pathophysiology of these
diseases in considerable detail, leading to significant insights into their
generation of motor disability. While genetically and clinically heterogeneous,
most of them are accompanied by prominent and characteristic changes in firing
rates and patterns in the basal ganglia, thalamus, and cortex. In recent years,
researchers have placed increasing emphasis on the importance of oscillatory
changes in firing in these structures, and have discovered that brain areas that
were previously considered to be remote from the basal ganglia (such as the
cerebellum and the pedunculopontine nucleus) are also highly significant in these
disorders. The evolving pathophysiologic concepts have important implications for
improving our understanding of the biology of these disorders, and for the
development of more effective pharmacologic and surgical therapies with fewer
side effects than seen with the currently available treatments. In this chapter,
the known pathophysiology of three common movement disorders, Parkinson's
disease, dystonia, and essential tremor, is reviewed.
PMID- 29332071
TI - Clinical Presentation and Prognosis of Common Movement Disorders.
AB - Great progress has been made in expanding our understanding of the natural
history of movement disorders, leading to impressive advancements in their
medical and surgical management. Movement disorders are a diverse group of
diseases, varying widely in clinical characteristics and evolution. Some are
monosymptomatic while others have associated motor and nonmotor features. Some
are static while others follow a progressive course. This chapter will review
common primary and secondary movement disorders: Parkinson disease and other
forms of Parkinsonism, essential tremor and its differential diagnoses, dystonia
and tic disorders. Herein, we will provide an overview of the clinical
presentation and prognosis of the primary and secondary movement disorders most
relevant to discussions of surgical candidacy.
PMID- 29332072
TI - Medical Management of Movement Disorders.
AB - Pharmacological treatment is the cornerstone in the management of movement
disorders. Although most available treatment options have no impact on the
underlying process of each movement disorder, symptomatic therapies can
significantly improve patient's quality of life and level of disability. Here, we
review the current knowledge on clinical symptomatic management of Parkinson's
disease (both early and advanced stages), essential tremor, dystonia, and chorea.
Ideally, treatment should be carried out by specialists with reasonable
experience in movement disorders, as it needs to be tailored for each patient
depending on several appraisals, including but not limited to patients' needs,
compliance issues, potential side effects, caregiver support, and presence of
comorbidities. When medications fail to improve patient's disability,
stereotactic surgery is a well-established option for most of these disorders.
PMID- 29332073
TI - Functional Anatomy of Basal Ganglia Circuits with the Cerebral Cortex and the
Cerebellum.
AB - The neural connections of the basal ganglia provide important insights into their
function. Here, we discuss the current perspective on basal ganglia connections
with the cerebral cortex and with the cerebellum. We review the evidence that the
basal ganglia participate in functionally segregated circuits with motor and non
motor areas of the cerebral cortex. We then discuss the data that the basal
ganglia are interconnected with the cerebellum. These results provide the
anatomical substrate for basal ganglia contributions not only to the control of
movement, but also to a variety of cognitive and affective functions.
Furthermore, these findings indicate that abnormal activity in basal ganglia
circuits with the cerebral cortex and with the cerebellum may contribute to both
motor and non-motor deficits associated with several neurologic and psychiatric
conditions.
PMID- 29332074
TI - Diffusion Tensor Imaging of the Basal Ganglia for Functional Neurosurgery
Applications.
AB - Since its introduction, diffusion tensor imaging (DTI) has become an important
tool in neuroscience given its unprecedented ability to image brain white matter
in vivo. The interest in understanding the mechanisms of action of Deep Brain
Stimulation in different targets and indications, together with the constant
drive towards the improvement in long-term clinical outcomes, has found a logical
complement in the application of tractography in this field. Diffusion tensor
imaging has been traditionally associated with an increased susceptibility to MRI
artifacts, and expensive computational resources. Recent advances have however
improved these restrictions, allowing for countless applications in Neurosurgery,
as demonstrated by the large number of original research papers published in the
last decade. In this chapter, we review the current status of the implementation
of DTI during DBS of the basal ganglia, discussing the findings, potential
challenges and the expected improvements in surgical outcomes deriving by the
routine use of tractography in functional neurosurgery.
PMID- 29332075
TI - Patient Evaluation and Selection for Movement Disorders Surgery: The Changing
Spectrum of Indications.
AB - This report summarizes the state-of-the-art and controversies around patient
selection for deep brain stimulation (DBS) for various conditions. Parkinson's
disease (PD): several class I studies have shown superiority of DBS over best
medical treatment for advanced PD with fluctuations and further inclusion
criteria. One class I study suggests that PD patients with early motor
complications might gain more quality of life if operated within 3 years after
the onset of fluctuations. The subthalamic nucleus (STN) is still the standard
target. STN DBS has an impact on impulse control disorders though the exact
mechanism is unclear. Tremor: essential tremor (ET) patients found to be eligible
for DBS surgery should first be treated with primidone, propranolol, and with a
combined therapy preoperatively. Second-line drugs (i.e., topiramate and
gabapentin) may be useful. No class I studies exist for DBS treatment of ET. The
optimal target of DBS in ET might be the posterior subthalamic area. Dystonia:
there is class I evidence for primary generalized and segmental dystonia and for
some botulinum-resistant focal dystonias. The impact of age, symptom duration,
and DYT-mutation status in primary dystonia on the outcome of DBS surgery clearly
demands more studies. DBS has a role in SCGE-mutation positive myoclonus dystonia
and tardive dystonia. Finally, neurostimulation in secondary dystonia might be
considered in selected patients based on an individual patient's approach.
PMID- 29332077
TI - Stereotactic Radiofrequency Lesioning for Movement Disorders.
AB - During the past 2 decades, deep brain stimulation (DBS) took over the position of
radiofrequency (RF) lesioning of thalamic or pallidal targets for control of
movement disorders. Superiority of DBS over RF lesioning is widely accepted, and
most neurosurgeons even regard RF lesioning to be old-fashioned and dangerous.
Such concepts emerged from the data of old stereotactic operations with
ventriculography and without computerized planning. Hardware-related
complications are not negligible in long-term DBS therapy, and DBS only controls
the symptoms. Living with an implanted device is also a burden for patients. With
modern stereotactic techniques, RF lesioning is safe and effective. Indication of
RF lesioning includes various types of tremor, focal hand dystonia, and even
generalized or segmental dystonias. Neurosurgeons armed with both the procedures
can choose the best treatment modality for patients.
PMID- 29332076
TI - Image-Guided, Asleep Deep Brain Stimulation.
AB - Deep brain stimulation (DBS) has become an established treatment for medically
refractory movement disorders including Parkinson's disease, essential tremor,
and dystonia. The field of DBS continues to evolve with advances in patient
selection, target identification, electrode and pulse generator technology, and
the development of more effective stimulation paradigms such as closed-loop
stimulation. Furthermore, as the safety and efficacy of DBS improves through
better hardware design and deeper understanding of its mechanisms of action, the
indications for DBS will continue to expand to cover a wider range of disorders.
Finally, the recent approval of MR-guided focused ultrasound for the treatment of
essential tremor and potentially other movement disorders heralds a resurgence in
lesion creation as a viable alternative to DBS for selected patients.
PMID- 29332078
TI - Magnetic Resonance-Guided High Intensity Focused Ultrasound for Treating Movement
Disorders.
AB - Transcranial magnetic resonance-guided focused ultrasound (MRgFUS) surgery has
recently gained favor as a novel, noninvasive alternative to conventional
neurosurgery. In contrast to traditional ablative interventions, transcranial
MRgFUS surgery is entirely imaging-guided and uses continuous temperature
measurements at the target and surrounding tissue taken in real-time. Unlike
Gamma Knife radiosurgery, MRgFUS surgery can make a lesion immediately and does
not use ionizing radiation. Moreover, since no metallic device is implanted, MR
imaging-based diagnosis is not restricted throughout life. An additional strength
of transcranial MRgFUS surgery is its ability to focus acoustic energy through
the intact skull onto deep-seated targets, while minimizing adjacent tissue
damage. Even though the established indications of MRgFUS include bone
metastases, uterine fibroids, and breast lesions, several promising preclinical
and phase I clinical trials of neuropathic pain, essential tremor, Parkinson's
disease (PD), and obsessive-compulsive disorder have demonstrated that the
delivery of focused ultrasound energy promises to be a broadly applicable
technique. For instance, this technique can be used to generate focal
intracranial thermal ablative lesions of brain tumors, or to silence
dysfunctional neural circuits and disrupt the blood-brain barrier for targeted
drug delivery and the modulation of neural activity. Here we review the general
principles of MRgFUS and its current applications, with a special focus on
movement disorders such as essential tremor and PD, and discuss controversies and
limitations of this technique.
PMID- 29332079
TI - Radiosurgical Thalamotomy.
AB - Tremor is a common movement disorder that can be disabling, and its initial
treatment is in the form of medical therapies. Often patients are refractory and
seek surgical intervention. Treatment options for these patients include surgical
radiofrequency thalamotomy and deep brain stimulation. There are a subset of
patients who, for various reasons, are not candidates for open surgical
procedures, or who opt to avoid them. For these patients, radiosurgical
thalamotomy is a safe and useful alternative. Herein, we provide a review of the
use of radiosurgical thalamotomy for the treatment of medically refractory tremor
by discussing its history, defining the technique and its indications, evaluating
its efficacy, and exploring its complications and shortcomings.
PMID- 29332080
TI - Radiosurgical Pallidotomy for Parkinson's Disease.
AB - Deep brain stimulation (DBS) has been widely accepted as a tool for treating many
symptoms of Parkinson's disease (PD); pallidotomy has been nearly abandoned.
Concerns about both the safety and efficacy of pallidotomy are based on small
series, isolated case reports, and techniques that would now be considered
obsolete. The senior author recently reviewed long-term follow-up of a series of
patients who had gamma knife pallidotomy (GKP) for advanced PD. GKP leads to
durable, clinically significant benefit. Bilateral GKP adds incremental
improvement. The complication rate was 4% when calculated on a per lesion basis.
GKP is not quite as effective as DBS for tremor and bradykinesia; the results of
GKP and DBS are equivalent for dyskinesia. GKP should be considered in patients
who are not candidates for DBS. GKP is not as invasive as radiofrequency
pallidotomy and avoids the problems and expenses associated with DBS. Patients on
anticoagulants, with cognitive deficits or with other contraindications to DBS
can be offered GKP to alleviate many of the motor symptoms of PD.
PMID- 29332081
TI - Radiosurgical Subthalamic Nucleotomy.
AB - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is the reference
technique in Parkinson's disease (PD) at different stages of complications. Some
patients cannot afford DBS due to anticoagulation or comorbidities or due to
pecuniary reasons. Radiosurgery is a minimally invasive stereotactic technique,
with no craniotomy and subsequently no risk of bleeding or infection. Its good
safety efficacy profile has been established in the treatment of tremor, and the
postoperative care issues are simple with a much shorter hospital stay (mean 48
h). The application of radiosurgery to STN target in PD as an alternative to DBS
is being debated. The lesion of the STN is presumed to induce hemiballism.
Experimental works suggest a potential lower risk of hemiballism in animal models
of PD. However, radiofrequency ablation of the STN is associated with a
significant rate of severe dyskinesia, sometimes permanent and severe enough to
request salvage pallidotomies. The positive experience of VIM radiosurgery in
tremor and its capacity to create precise, accurate and well-controlled lesions
provides reasonable rationale for the evaluation of this technique when applied
to STN in PD. Preliminary results till date have shown the absence of severe
permanent dyskinesia. Prospective controlled trials are mandatory to evaluate the
safety efficacy of this technique in PD.
PMID- 29332082
TI - Frameless Functional Stereotactic Approaches.
AB - The stereotactic frame has served as the gold standard apparatus for accurate and
precise targeting of deep brain structures since 1947. Despite passing the test
of time, the stereotactic frame has several limitations from the perspective of
both neurosurgeons and patients. Therefore, there was a need to develop a
frameless system that had equivalent accuracy and reliability to the frame. This
need was met with 3 commercially available frameless stereotactic systems
designed specifically for deep brain stimulation surgery: Nexframe, STarFix, and
ClearPoint. Over the past decade, the frameless and frame-based systems have been
extensively investigated by numerous studies and found to be equivalent in
experimental and clinical accuracy as well as in clinical outcomes. This chapter
summarizes the findings of those studies along with the discussion of sources of
stereotactic errors. The procedural aspects, advantages, and disadvantages of
each frameless system are reviewed. Frameless stereotaxy is a safe, accurate, and
effective technique for functional stereotactic approaches and provides a viable
alternative to the frame-based systems.
PMID- 29332083
TI - Deep Brain Stimulation: Interventional and Intraoperative MRI Approaches.
AB - Interventional and intraoperative MRI approaches to deep brain stimulator
implantation are relatively new, and in their purest form represent a distinct
departure from traditional stereotactic techniques. They employ a novel means of
stereotaxis based on regions of interest in the MR space and simple geometric
principles, which eliminate the need for a stereotactic frame. This approach is
appropriate for targets that are MR visible, and for whom the local anatomy and
function are well characterized. It may also be appropriate for targets that do
not have a well-described physiologic signature and for which clinical response
to macrostimulation does not play a critical role. We will discuss the rationale
and principles of this new technique as well as its advantages and disadvantages
relative to awake, physiologically guided deep brain stimulation surgery.
PMID- 29332084
TI - Thalamic Deep Brain Stimulation.
AB - The use of deep brain stimulation (DBS) of the thalamus has been proven to be a
safe and efficacious treatment for the management of many diseases. The most
common indication for thalamic DBS remains essential tremor (ET), one of the most
common movement disorders in the world. ET patients should be considered for
surgical intervention when their tremor has demonstrated to be refractory to
medication, a characteristic estimated to be present in roughly 50% of ET cases.
Advantages of DBS over thalamotomy include its reversibility, the ability to
adjust stimulation settings to optimize efficacy and minimize side effects, the
ability to perform bilateral procedures safely, and an association with a lower
risk of postoperative cognitive problems. The most common target of DBS for ET is
the ventralis intermedius (VIM) of the thalamus, and the optimal electrode
location corresponds to the anterior margin of the VIM. Other indications for
thalamic DBS include non-ET tremor, obsessive-compulsive disorder, neuropathic
pain, traumatic brain injury, Tourette's syndrome, and drug-resistant epilepsy
among others.
PMID- 29332085
TI - Deep Brain Stimulation of the Subthalamic Nucleus and Globus Pallidus for
Parkinson's Disease.
AB - The concept of deep brain stimulation (DBS) for Parkinson's disease (PD) was
introduced over 20 years ago, but our understanding of the nuances of this
procedure continues to improve. The average motor outcomes of internal segment of
the globus pallidus (GPi) and subthalamic nucleus (STN) DBS appear to be similar,
although GPi DBS may allow greater recovery of verbal fluency and may provide
greater relief of depression symptoms and improvement in the quality of life, and
STN DBS appears more likely to result in decrease in levodopa equivalent doses.
Despite the lack of consensus on whether STN or GPi DBS is most appropriate for a
given clinical phenotype, the general expansion of patient selection criteria to
include younger and older patients and the advent of real-time imaging-confirmed
that DBS electrode placement are making life-changing treatment available to
greater numbers of movement disorder patients.
PMID- 29332086
TI - Current and Expected Advances in Deep Brain Stimulation for Movement Disorders.
AB - Deep brain stimulation (DBS) has become an established treatment for medically
refractory movement disorders including Parkinson's disease, essential tremor,
and dystonia. The field of DBS continues to evolve with advances in patient
selection, target identification, electrode and pulse generator technology, and
the development of more effective stimulation paradigms such as closed-loop
stimulation. Furthermore, as the safety and efficacy of DBS improves through
better hardware design and deeper understanding of its mechanisms of action, the
indications for DBS will continue to expand to cover a wider range of disorders.
Finally, the recent approval of MR-guided focused ultrasound for the treatment of
essential tremor and potentially other movement disorders heralds a resurgence in
lesion creation as a viable alternative to DBS for selected patients.
PMID- 29332087
TI - Adaptive Brain Stimulation for Movement Disorders.
AB - Deep brain stimulation (DBS) has markedly changed how we treat movement disorders
including Parkinson's disease (PD), dystonia, and essential tremor (ET). However,
despite its demonstrable clinical benefit, DBS is often limited by side effects
and partial efficacy. These limitations may be due in part to the fact that DBS
interferes with both pathological and physiological neural activities. DBS could,
therefore, be potentially improved were it applied selectively and only at times
of enhanced pathological activity. This form of stimulation is known as closed
loop or adaptive DBS (aDBS). An aDBS approach has been shown to be superior to
conventional DBS in PD in primates using cortical neuronal spike triggering and
in humans employing local field potential biomarkers. Likewise, aDBS studies for
essential and Parkinsonian tremor are advancing and show great promise, using
both peripheral or central sensing and stimulation. aDBS has not yet been trialed
in dystonia and yet exciting and promising biomarkers suggest it could be
beneficial here too. In this chapter, we will review the existing literature on
aDBS in movement disorders and explore potential biomarkers and stimulation
algorithms for applying aDBS in PD, ET, and dystonia.
PMID- 29332088
TI - Drug Delivery for Movement Disorders.
AB - There has been substantial research interest in delivering therapeutic
neurotrophic factors directly to the brain for the treatment of Parkinson's
Disease (PD) and other movement disorders. Direct infusion of glial cell-line
derived neurotrophic factor has been investigated in both pre-clinical models and
clinical trials. In this chapter we discuss past and present research
investigating the potential of direct drug delivery to the brain for the
treatment of PD and other movement disorders.
PMID- 29332089
TI - Gene Therapy for Parkinson's Disease.
AB - Gene therapy is a clinical tool that may eventually provide therapeutic benefit
to patients suffering from movement disorders through a few potential mechanisms:
direct correction of the pathogenic mechanism, neuroprotection, neurorestoration
or symptom control. The therapeutic mechanism is therefore dependent on knowledge
of disease pathogenesis and the required temporal and spatial specificities of
gene expression. An additional critical challenge is achieving the most complete
transduction of the target structure while avoiding leakage into neighboring
regions or perivascular spaces. Although critical clinical work is ongoing to
optimize the direct intracerebral delivery of transgenes to the brain, the field
has recently entered a new technological era, where interventional-MRI-guided
convection-enhanced delivery is the gold standard for verifying accurate vector
delivery in real-time.
PMID- 29332090
TI - Impaired Value of 99m Tc-GSA Scintigraphy as an Independent Risk Factor for
Posthepatectomy Liver Failure in Patients with Hepatocellular Carcinoma.
AB - BACKGROUND: Posthepatectomy liver failure (PHLF) was recently defined with the
corresponding recommendations as follows: grade A, no change in clinical
management; grade B, clinical management with noninvasive treatment; and grade C,
clinical management with invasive treatment. In this study, we identified the
risk factors for grade B and C PHLF in patients with hepatocellular carcinoma
(HCC). METHODS: Of 339 HCC patients who underwent curative hepatic resection, 218
were included for analysis. The LHL15 index (uptake ratio of the liver to that of
the liver and heart at 15 min) was measured by 99m Tc-GSA (99m technetium
labelled galactosyl human serum albumin); remnant LHL15 was calculated as LHL15 *
[1 - (resected liver weight - tumor volume)/whole liver volume without tumor].
RESULTS: A total of 163 patients were classified as having no PHLF, whereas 17,
37, and 1 patient had PHLF grade A, B, and C, respectively. There were
significant differences in indocyanine green R15, serum albumin, prothrombin
time, Child-Pugh classification, LHL15 and remnant LHL15 between patients with
grades B/C PHLF and patients with grade A or no PHLF. Only remnant LHL15 was
identified as an independent risk factor for grades B/C PHLF (p = 0.023), with a
cut-off value of 0.755. CONCLUSIONS: Remnant LHL15 was an independent risk factor
for grades B/C PHLF. Patients with impaired remnant LHL15 value of <0.755 should
be carefully monitored for PHLF.
PMID- 29332091
TI - The Association among Default Mode Network Functional Connectivity,
Mentalization, and Psychopathology in a Nonclinical Sample: An eLORETA Study.
AB - AIMS: We investigated default mode network (DMN) electroencephalography (EEG)
functional connectivity differences between individuals with self-reported high
mentalization capability and low psychopathological symptoms, versus participants
with mentalization impairments and high psychopathological symptoms. METHODS:
Forty-nine students (35 women) with a mean age of 22.92 +/- 2.53 years were
administered the Mentalization Questionnaire (MZQ) and the Symptom Checklist-90
Revised. Five minutes of EEG during resting state were also recorded for each
participant. DMN functional connectivity analyses were conducted by means of the
exact Low Resolution Electric Tomography software (eLORETA). RESULTS: Compared to
the individuals with high mentalization capability and lower self-reported
psychopathological symptoms, participants with mentalization impairments and high
psychopathological symptoms showed a decrease of EEG beta connectivity between:
(i) the right and left medial frontal lobe, and (ii) the left medial frontal lobe
and the right anterior cingulate cortex. Furthermore, while MZQ total score was
positively associated with DMN network connections (i.e., right and left medial
frontal lobes), several psychopathological symptoms (i.e., interpersonal
sensitivity, depression, and psychoticism) were negatively associated with DMN
connectivity. CONCLUSION: Our results may reflect a top-down emotion regulation
deficit which is associated with both internalizing and externalizing behavior
problems.
PMID- 29332092
TI - Early Life Stress Activates Glial Cells in the Hippocampus but Attenuates
Cytokine Secretion in Response to an Immune Challenge in Rat Pups.
AB - OBJECTIVE: Early life stress (ELS) increases the vulnerability to developing
psychopathological disorders in adulthood that are accompanied by brain
inflammatory processes. However, it is not known how a combined double hit
(stress and immune) at an early age affects the response of the neuroimmune
system. Here we investigated the effect of periodic maternal separation (MS)
followed by administration of lipopolysaccharide (LPS) on glial cells in the CA3
region and hilus of the hippocampus and on cytokine release on postnatal day (PN)
15. METHODS: Male rat pups were subjected to MS (3 h/day, PN1-14). MS and control
pups received a single LPS injection (1 mg/kg of body weight) on PN14. They were
subjected to an open field test 1 h later. The pups were sacrificed 90 min after
LPS injection (PN14) or on PN15 for cytokine or immunohistological analyses,
respectively. RESULTS: LPS reduced the locomotion and induced high corticosterone
levels in treated pups. MS or LPS reduced microglial density and activated
microglial cells in the hippocampal CA3 and hilus regions. Microglial activation
was highest in MS-LPS pups. The astrocyte density was mildly reduced by MS or LPS
in the CA3 region and hilus, but the reduction was maximal in MS-LPS pups. LPS
increased the secretion of plasmatic interleukin (IL)-1beta, tumor necrosis
factor-alpha, and IL-6, and of hippocampal IL-1beta protein, but these were
attenuated in MS-LPS pups. CONCLUSION: Although MS and LPS activate neuroimmune
cells, stress attenuates the hippocampal and peripheral cytokine response to LPS
through an as-yet unidentified adaptive mechanism. These results provide
information regarding the neurobiology of stress and inflammation.
PMID- 29332093
TI - Structure-Function Correlation in Hemianopic Vision Loss in Children Aged 3-6
Years Using OCT and SVOP, and Comparison with Adult Eyes.
AB - PURPOSE: To correlate visual field assessment with saccadic vector optokinetic
perimetry (SVOP) in children with ganglion cell loss due to anterior pathway
pathologies resulting in hemianopic visual field defects measured with optical
coherence tomography (OCT). METHODS: 5 young (aged 3-6 years) and 5 adult
patients with hemianopia, 10 healthy preschoolers (mean age 4.4 years), and 10
healthy adults (mean age 25.3 years) were tested with SVOP and OCT (focusing on
the ganglion cell layer, GCL+). In adults, visual field testing was also
performed with static and fundus-controlled perimetry. RESULTS: OCT allowed
precise structure analysis and showed a vertical border with GCL+ loss on the
hemianopic side in children and adults compared to controls. SVOP showed visual
field defects on the hemianopic side in peripheral regions and inadequate results
at the parafoveal positions in both groups. In contrast, static and fundus
controlled perimetry showed a clear border in foveal and parafoveal regions.
CONCLUSIONS: All children underwent SVOP with minimal restrictions, allowing
functional evaluation of peripheral visual field positions. Parafoveal positions
showed multiple false-positive results. The function-structure relationship is
measurable even in young children by using the GCL+ analysis. This combination of
novel child-friendly techniques allows collecting objectively measured values and
simplifies diagnosis and follow-up in treatment.
PMID- 29332094
TI - Low-Dose Oral Immunotherapy Using Low-Egg-Allergen Cookies for Severe Egg
Allergic Children Reduces Allergy Severity and Affects Allergen-Specific
Antibodies in Serum.
AB - BACKGROUND: We evaluated the safety and efficacy of low-egg-allergen cookies
(LAC) as low-dose oral immunotherapy (OIT) in children with severe egg allergy.
We also examined the relationship between mild desensitization by low-dose OIT
and serum biomarkers of allergy. METHODS: We enrolled 13 children with egg
allergy who could not receive OIT with hard-boiled egg white (EW). For 11
participants, OIT was carried out using LAC for 3-4 months. Open food challenges
with hard-boiled EW and blood samplings were performed before and after OIT.
Participants were divided into 2 groups: high effect (H-E) and no/low effect (N/L
E). Serum levels of total IgE and egg yolk-, EW-, and ovomucoid (OM)-specific
IgE, ovalbumin (OVA)- and OM-specific IgG4, IgA1, and IgA2, and the percentage of
CD 203c+ were measured. RESULTS: Allergic severity was reduced in 7 patients, who
were assigned to the H-E group. Moreover, no study participants were taken off
the intake of LAC during OIT. In the H-E group, OVA-specific IgA2 levels after
OIT were significantly higher than before OIT. The ratios of OM-specific IgG4/OM
specific IgE and OM-specific IgA2/OM-specific IgE in the H-E group after OIT were
significantly higher than before OIT. CONCLUSION: Our findings suggest that low
dose OIT using LAC is an effective and safe treatment for patients with severe
egg allergy.
PMID- 29332095
TI - Both Serum Brain-Derived Neurotrophic Factor and Interleukin-6 Levels Are Not
Associated with Therapeutic Response to Lamotrigine Augmentation Therapy in
Treatment-Resistant Depressive Disorder.
AB - BACKGROUND/AIMS: Serum levels of brain-derived neurotrophic factor (BDNF) and
interleukin-6 (IL-6) were prospectively monitored in relation with therapeutic
response to lamotrigine augmentation therapy in 46 (15 males and 31 females)
inpatients with treatment-resistant depressive disorder during an 8-week
treatment with lamotrigine using an open-study design. METHODS: The subjects were
46 depressed patients who had already shown insufficient response to at least 3
psychotropics including antidepressants, mood stabilizers, and atypical
antipsychotics. The diagnoses were major depressive disorder (n = 19), bipolar I
disorder (n = 6), and bipolar II disorder (n = 22). The final doses of
lamotrigine were 100 mg/day for 26 subjects who were not taking valproate and 75
mg/day for 20 subjects taking valproate, respectively. Depressive symptoms were
evaluated by the Montgomery-Asberg Depression Rating Scale (MADRS) before and
after the 8-week treatment. Blood sampling was performed before the start of
lamotrigine treatment and at week 8. Serum BDNF and IL-6 levels were measured
using quantitative sandwich enzyme immunoassays. RESULTS: No significant changes
in serum BDNF or IL-6 levels during the 8-week lamotrigine treatment were
observed in the total of subjects, responders or nonresponders. There was no
significant correlation between the changes in serum BDNF or IL-6 levels and the
percent improvement in MADRS scores in the overall subjects. CONCLUSION: The
present study suggests that the acute effect of lamotrigine augmentation therapy
for a major depressive episode is not related to either BDNF or IL-6, at least in
patients with treatment-resistant depressive disorder.
PMID- 29332096
TI - Higher Thrombin-Antithrombin III Complex Levels May Indicate Severe Acute
Pancreatitis.
AB - AIM: Coagulation disorders may develop in association with severe acute
pancreatitis (AP). Plasma thrombin-antithrombin III complex (TAT) levels are one
of the principal markers of coagulation disorder. The purpose of this study was
to evaluate TAT and other hemostatic parameters in patients with AP and to
examine whether or not these parameters indicate the severity of AP. METHOD:
Forty-six patients with AP (14 severe, 32 non-severe) and a 30-member healthy
control group were recruited. The severity of AP was determined using the revised
Atlanta classification. ELISA was used to measure patients' plasma TAT levels.
RESULTS: The TAT levels of AP patients at presentation were higher than those of
the control group (p = 0.005). The plasma TAT levels of patients with severe AP
were also significantly higher than those of patients with non-severe AP (p =
0.05) and of the control group (p < 0.001). The general accuracy, sensitivity and
specificity of TAT levels in predicting the severity of AP were 77.4, 77.8, and
77.3% respectively. CONCLUSION: The coagulation cascade was activated in the AP
patients in our study, and this was shown to become more pronounced as severity
of the disease increased. Plasma TAT levels at the time of presentation in
patients with AP can be used as a marker for predicting the severity of the
disease.
PMID- 29332098
TI - A Novel Mutation of the delta-Globin Gene in an Asymptomatic 30-Year-Old Female.
PMID- 29332097
TI - Is the Atopy Patch Test Reliable in the Evaluation of Food Allergy-Related Atopic
Dermatitis?
AB - BACKGROUND: Aeroallergens and food allergens are found to be relevant in atopic
dermatitis. The atopy patch test (APT) can help to detect food allergies in
children with atopic dermatitis. This study evaluates if the APT is a valuable
tool in the diagnostic workup of children with food allergy-related atopic
dermatitis. METHODS: 42 children between 6 months and 12 years of age were
selected at the Mofid Children Hospital. Atopic dermatitis was diagnosed, and the
severity of the disease was determined. At the test visit, the patients underwent
a skin prick test (SPT), APT, and serum IgE level measurement for cow's milk, egg
yolk, egg white, wheat, and soy. RESULTS: We found a sensitivity of 91.7%, a
specificity of 72.7%, a positive predictive value (PPV) of 88%, a negative
predictive value (NPV) of 80%, and an accuracy of 85.7% for APT performed for
cow's milk. APT performed for egg yolk had a sensitivity and a NPV of 100%, while
the same parameters obtained with egg white were 84.2 and 75%, respectively. The
sensitivity, specificity, and NPV of the APT for wheat were 100, 75, and 100%,
respectively. The sensitivity, PPV, and NPV of the APT for soy were 87.5, 70, and
87.5%, respectively. CONCLUSIONS: Our data demonstrate that the APT is a reliable
diagnostic tool to evaluate suspected food allergy-related skin symptoms in
childhood and infancy.
PMID- 29332099
TI - Association between the Intron 8 VNTR Polymorphism of the DAT1 Gene and Crack
Cocaine Addiction.
AB - BACKGROUND: This study aims to compare allele and genotype frequencies of a 30-bp
variable number of tandem repeats (VNTR) polymorphism of the DAT1 gene, located
at intron 8, between adult crack cocaine users and nonaddicted individuals. Due
to its involvement in drug addiction, this gene is a good candidate for molecular
studies. METHODS: A cross-sectional sample of 239 current adult crack abusers or
dependents from in- and outpatient clinics and 211 control individuals was
collected in Brazil. They were evaluated using ASRS, ASI-6, WAIS-III, and MINI
assessments. DNA samples extracted from whole blood were genotyped for the intron
8 VNTR in DAT1. RESULTS: Logistic regression analysis was performed and
controlled for gender, age, ethnicity, educational level, and comorbidities of
clinical interest (generalized anxiety disorder, suicide risk, major depressive
episode, and attention deficit/hyperactivity disorder). This analysis showed that
the 6R6R genotype was associated with crack cocaine addiction (OR = 1.844; CI =
1.101-3.089; p = 0.020). CONCLUSIONS: Our results are consistent with the role of
DAT1 in the neurobiology of drug addiction. Nevertheless, the study of other
genes, environmental factors, and their interactions is also important to gain a
broader understanding of this condition.
PMID- 29332101
TI - Is Kinesio Taping to Generate Skin Convolutions Effective for Increasing Local
Blood Circulation?
AB - BACKGROUND It is unclear whether traditional application of Kinesio taping, which
produces wrinkles in the skin, is effective for improving blood circulation. This
study investigated local skin temperature changes after the application of an
elastic therapeutic tape using convolution and non-convolution taping methods
(CTM/NCTM). MATERIAL AND METHODS Twenty-eight pain-free men underwent CTM and
NCTM randomly applied to the right and left sides of the lower back. Using
infrared thermography, skin temperature was measured before, immediately after
application, 5 min later, 15 min later, and after the removal of the tape.
RESULTS Both CTM and NCTM showed a slight, but significant, decrease in skin
temperature for up to 5 min. The skin temperature at 15 min and after the removal
of the tape was not significantly different from the initial temperature for CTM
and NCTM. There were also no significant differences in the skin temperatures
between CTM and NCTM. CONCLUSIONS Our findings do not support a therapeutic
effect of wrinkling the skin with elastic tape application as a technique to
increase local blood flow.
PMID- 29332102
TI - Saudi Medical Journal 2017.
AB - [No Abstract Available].
PMID- 29332100
TI - Robot-Assisted Radical Prostatectomy Is More Beneficial for Prostate Cancer
Patients: A System Review and Meta-Analysis.
AB - BACKGROUND Robot-assisted radical prostatectomy (RARP) is increasingly used
worldwide, but comparisons of perioperative, functional, and oncologic outcomes
among RARP, laparoscopic radical prostatectomy (LRP), and open radical
prostatectomy (ORP) remain inconsistent. MATERIAL AND METHODS Systematic
literature searches were conducted using EMBASE, PubMed, the Cochrane Library,
CNKI, and Science Direct/Elsevier up to April 2017. A meta-analysis was conducted
using Review Manager and Stata software. RESULTS We included 33 studies. Meta
analysis revealed that blood loss, transfusion rate, and positive surgical margin
(PSM) rate were significantly lower following RARP compared with LRP (SMD (95%
confidence interval [CI]) 0.31 [0.01, 0.61]; combined ORs (95% CI) 5.32 [1.29,
21.98]; 1.27 [1.10, 1.46]) and ORP (SMD (95% CI) 0.75 [0.30, 1.21]; and combined
ORs (95% CI) 3.44 [1.21, 9.79]); positive surgical margin (PSM) rates were
significantly lower following RARP compared with LRP (combined ORs (95% CI) 1.27
[1.10, 1.46]), but not ORP. Operation time was also shorter for RARP than for
LRP. The rates of nerve-sparing, recovery of complete urinary continence, and
recovery of erectile function were significantly higher following RARP compared
with LRP (combined ORs (95% CI) 0.55 [0.31, 0.95]; 0.66 [0.55, 0.78]; 0.46 [0.30,
0.71]) and ORP (combined ORs (95% CI) 0.36 [0.21, 0.63]; 0.33 [0.15, 0.74]; 0.65
[0.37, 1.14]). CONCLUSIONS This meta-analysis demonstrates that RARP results in
better overall outcomes than LRP and ORP in terms of blood loss, transfusion
rate, nerve sparing, urinary continence and erectile dysfunction recovery, and
suggests that RARP offers better results than LRP and ORP in treatment of
prostate cancer. However, studies with larger sample sizes and long-term results
are needed.
PMID- 29332103
TI - Proteomic effects of wet cupping (Al-hijamah).
AB - Wet cupping (Al-hijamah) is a therapeutic technique practiced worldwide as a part
of the Unani system of medicine. It involves bloodletting from acupoints on a
patient's skin to produce a therapeutic outcome. A thorough review of research
articles on wet cupping with relevance to proteomics field that are indexed by
Google Scholar, PubMed, and/or Science Direct databases was performed. Eight
original research articles were summarized in this paper. Overall, wet cupping
did not have a significant effect on C-reactive protein, Hsp-27, sister chromatid
exchanges, and cell replication index. In contrast, wet cupping was found to
produce higher oxygen saturation, eliminate lactate from subcutaneous tissues,
remove blood containing higher levels of malondialdehyde and nitric oxide, and
produce higher activity of myeloperoxidase. The proteomic effects of wet cupping
therapy have not been adequately investigated. Thus, future studies on wet
cupping that use systemic and sound protocols to avoid bias should be conducted.
PMID- 29332104
TI - Assessment of the fit of removable partial denture fabricated by computer-aided
designing/computer aided manufacturing technology.
AB - OBJECTIVE: To assess the level of evidence that supports the quality of fit for
removable partial denture (RPD) fabricated by computer-aided designing/computer
aided manufacturing (CAD/CAM) and rapid prototyping (RP) technology. Methods: An
electronic search was performed in Google Scholar, PubMed, and Cochrane library
search engines, using Boolean operators. All articles published in English and
published in the period from 1950 until April 2017 were eligible to be included
in this review. The total number of articles contained the search terms in any
part of the article (including titles, abstracts, or article texts) were
screened, which resulted in 214 articles. After exclusion of irrelevant and
duplicated articles, 12 papers were included in this systematic review. Results:
All the included studies were case reports, except one study, which was a case
series that recruited 10 study participants. The visual and tactile examination
in the cast or clinically in the patient's mouth was the most-used method for
assessment of the fit of RPDs. From all included studies, only one has assessed
the internal fit between RPDs and oral tissues using silicone registration
material. The vast majority of included studies found that the fit of RPDs ranged
from satisfactory to excellent fit. Conclusion: Despite the lack of clinical
trials that provide strong evidence, the available evidence supported the claim
of good fit of RPDs fabricated by new technologies using CAD/CAM.
PMID- 29332105
TI - The emergence of carbapenem-resistant Klebsiella pneumoniae isolates producing
OXA-48 and NDM in the Southern (Asir) province, Saudi Arabia.
AB - OBJECTIVES: To identify the prevalence of carbapenem-resistant Klebsiella
pneumoniae (CRKP) and the most common types of cabapenemases among CRKP in the
Southern (Asir) province hospitals, Saudi Arabia. Methods: The cross-sectional
study was conducted between late April and September in 2015. A total of 54
Klebsiella pneumoniae (K. pneumoniae) isolates with reduced sensitivity to
carbapenems were obtained from various clinical specimens of the 2 largest
hospitals in the Southern province. Minimum inhibitory concentrations (MICs) of
carbapenems were confirmed using E-test. Molecular detection of the most common
carbapenemase genes (blaIMP, bla-carbapenem-hydrolyzing oxacillinase [OXA-48],
blaVIM, bla-New Delhi metallo-beta-lactamas [NDM], and blaKPC) was performed
using multiplex-polymerase chain reaction. Results: The current study found that
increasing age and intensive care unit admission were associated with CRKP
isolation. The major type of carbapenemases was OXA-48 with 81.5% (n=44) and it
seems to reach an endemic level. New Delhi metallo-beta-lactamas (NDM) was the
second most frequent carbapenemase by 7.4% (n=4) of isolates while Verona
integron-encoded metallo-beta-lactamase (VIM) was reported only in one isolate.
Conclusion: Saudi Arabia receives large numbers of visitors and migrant workers
from OXA-48 and NDM endemic countries such as Turkey, India, and Pakistan every
year.
PMID- 29332106
TI - Single-center experience in the surgical treatment of combined lung
Echinococcosis.
AB - OBJECTIVES: To compare results of surgical treatment and complications of
patients with unilateral or bilateral thoracic and combined pulmonary
echinococcosis. METHODS: This cross-sectional analysis of a prospective study was
conducted in the Department of Thoracic and Pediatric Surgery, Scientific Center
of Surgery, Almaty, Kazakhstan among 598 patients with pulmonary echinococcosis,
who had surgical treatment with various surgical methods, depending on the
prevalence of echinococcosis, as follows: right lung in 357 (59.5%) patients,
left lung in 243 (40.5%) patients, bilateral in 95 (15.8%) patients, and
complicated echinococcosis in 317 (52.8%) patients. Length of stay per hospital
stay has been decreased (p less than 0.0001) by video-thoracoscopic
echinococcectomy with the high-energy laser (HEL) treatment of cyst, than after
echinococcectomy by cyst treatment with povidone-iodine. Treatment with formalin
presented the most longest hospital stay (p less than 0.0001). RESULTS:
Comparative analysis of patients with uncomplicated and complicated pulmonary
echinococcosis showed a high frequency of postoperative complications associated
with complicated echinococcosis (OR = 2.2, p less than 0.0001). Conclusion:
Despite the success of surgical treatment of pulmonary echinococcosis, issues of
intraoperative dissemination and safety remain, and treatment success rates can
be improved. These factors require further prospective multicenter studies.
PMID- 29332107
TI - The sleep architecture of Saudi Arabian patients with Kleine-Levin syndrome.
AB - OBJECTIVES: To establish baseline sleep architecture during an acute attack of
Kleine-Levin syndrome (KLS) in a cohort of Saudi Arabian KLS patients and compare
these characteristics with other published cohorts. Methods: This was a
retrospective cohort study of the polysomnographic characteristics of 10 typical
symptomatic Saudi Arabian KLS patients attending the University Sleep Disorders
Center, King Saud University, Riyadh, Saudi Arabia between 2002 and 2015. Data
were captured by nocturnal polysomnography during an acute attack of hypersomnia
and compared with other published cohorts identified via a systematic literature
search. Results: Self-reported time asleep during episodes (11.1+/-6.7 hours)
and recorded total sleep time (TST) (322.5+/-108.7 minutes) were generally
shorter than other published cohorts. Sleep efficiency was poor at 75.0%+/-25.1%,
with low relative amounts of rapid eye movement (REM) sleep (16.5+/-5.9% of TST)
and deep non-REM sleep (stage N3; 10.5+/-6.0% of TST) and high relative amounts
of non-REM sleep (stage N1; 7.0+/-4.3% of TST). The sleep architecture of Saudi
Arabian KLS patients was similar to other published cohorts. Conclusions: Sleep
architecture of our cohort was relatively normal and broadly similar to other
published studies, the main features being low sleep efficiency and low relative
amounts of REM and stage N3 sleep. Time-course polysomnography studies with
functional imaging may be useful to further establish the exact pathophysiology
of this disease.
PMID- 29332108
TI - Impact of body mass index on high blood pressure among obese children in the
western region of Saudi Arabia.
AB - OBJECTIVES: To evaluate the impact of body mass index (BMI) on high blood
pressure among obese children and adolescents in western region, Saudi Arabia.
Methods: Cross-sectional data were obtained from 306 (female: 140, male: 166)
child, between August 2016 and March 2017. A questioner was filled by health
professionals at ambulatory pediatric clinic followed by waist-hip circumference,
height, weight, and blood pressure measurement. Diastolic blood pressure (DBP)
and systolic blood pressure (SBP) were adjusted to gender, height, and age. World
Health Organization growth standards were used to calculate BMI z-scores.
Results: The mean age of subjects was 10.1 years. Body mass index increased SBP
by 1.722 mmHg (p=0.001), and DBP by 0.901 mmHg (p=0.006) in boys, and 0.969 mmHg
(p=0.036), and DBP by 0.704 mmHg (p=0.045) in girls. Waist hip ratio showed
significant difference p=0.041, (p=0.0001) between male and female. Of the
baseline characteristics, age greater than 11 years showed significant
difference. Symptomatic manifestation of high blood pressure, family history of
hypertension, level of activity, income level and post-secondary education in
parents, did not show any significant results. Conclusion: Elevated BMI is
associated with significantly increased diastolic and systolic blood pressure in
obese children, especially in children older than 11 years.
PMID- 29332109
TI - Prevalence of attention deficit hyperactivity disorder and comorbid psychiatric
and behavioral problems among primary school students in western Saudi Arabia.
AB - OBJECTIVES: To determine the prevalence of attention deficit hyperactivity
disorder (ADHD), subtypes of ADHD, and psychiatric, academic, and behavioral
comorbidity in public primary school students in Jeddah, Saudi Arabia. Methods:
This is a cross-sectional study. A simple random sample of 6 primary government
schools in Jeddah, Saudi Arabia, was identified (3 male, 3 female), and a random
sample of classes in each of grades 1-6 were selected. Between July and November
2016, teachers in these classes were asked to complete the Vanderbilt ADHD scale
on all students in their classes. Results: A total of 929 students were
screened. The overall prevalence of ADHD was 5% (5.3% in girls, 4.7% in boys).
The most prevalent subtype of ADHD was combined type (2.7%), followed by
hyperactive type (1.2%), and inattentive type (1.1%). The highest prevalence of
ADHD overall was in grade 3 (7.1%) and the lowest prevalence in grade 6 (3.4%).
Among students with ADHD, prevalence of comorbid psychiatric, academic, and
behavioral problems was widespread (56.5% oppositional defiant disorder/conduct
disorder, 54.4% impaired academic performance, 44.4% classroom behavioral
problems, 41.3% depression/anxiety). Comorbid problems were especially prevalent
in combined ADHD subtype and in boys. Conclusions: Attention deficit
hyperactivity disorder is common in primary school children in Jeddah, and is
associated with widespread psychiatric, academic, and behavioral problems,
especially in boys. These findings have implications for the diagnosis and
treatment of this serious neurobehavioral disorder.
PMID- 29332111
TI - Prevalence of menstrual problems and their association with psychological stress
in young female students studying health sciences.
AB - OBJECTIVES: To identify the prevalence of various menstrual problems in young
females studying health sciences and to identify their association with academic
stress. Methods: This was a cross-sectional study, conducted in the health
colleges of Immam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia between
February 2015 and February 2016. Seven hundred and thirty-eight female students
aged 18-25 years anonymously completed menstrual problem identification and
perceived stress scale questionnaire. The data was analyzed using the Statistical
Package for Social Sciences version 16.0. Results: Ninety-one percent of the
students were suffering from some kind of menstrual problem. The different
menstrual problems reported, and their incidences included irregular menstruation
(27%), abnormal vaginal bleeding (9.3%), amenorrhea (9.2%), menorrhagia (3.4%),
dysmenorrhea (89.7%), and premenstrual symptoms (46.7%). High perceived stress
(HPS) was identified in 39% of the students. A significant positive correlation
was found between HPS and menstrual problems. Students with HPS had 4 times, 2
times, and 2.8 times increased odds ratio for experiencing amenorrhea,
dysmenorrhea, and premenstrual syndrome (p less than 0.05). Conclusion: The most
prevalent menstrual problems (dysmenorrhea and premenstrual symptoms) in the
target population were strongly associated with stress. Therefore, it is
recommended that health science students should be provided with early
psychological and gynecological counselling to prevent future complications.
PMID- 29332110
TI - Association of psychological stress with skin symptoms among medical students.
AB - OBJECTIVES: To evaluate the association between psychological stress and skin
symptoms among medical students. Methods: A cross-sectional study was carried
out between January and June 2015. Electronic survey consists of Perceived Stress
Questionnaire (PSQ) and Self-Reported Skin Complaints Questionnaire were
distributed to all 1435 undergraduate students at College of Medicine, King Saud
University (KSU), Riyadh, Saudi Arabia. Results: Final analysis was performed on
data from 529 (36.9%) students. Students were divided into three groups: least
stressed students, n=135, PSQ index less than 0.39; highly stressed students,
n=136, PSQ index greater than 0.61; and moderately stressed students, n=258.
Older age, female gender, during exam weeks, and fourth and fifth years of
medical school (all p less than 0.01) were associated with the highest perceived
stress levels. When compared to least stressed students, highly stressed students
suffered from more oily, waxy patches or flakes on scalp (p<=0.0001), dry/sore
rash (p<=0.0001), warts (p<=0.0001), pimples (p<=0.0001), itchy skin (p<=0.0001),
hands itchy rash (p<=0.0001), hair loss (p<=0.0001), pull-out own hair (p=0.008),
scaly skin (p=0.012), troublesome sweating (p=0.016), nails biting (p=0.028), and
other rashes on face (p= 0.028). Conclusion: Various common skin conditions
could appear in context of psychological stress among medical students.
PMID- 29332112
TI - Evaluation of effectiveness of peer education on smoking behavior among high
school students.
AB - OBJECTIVES: To evaluate the effectiveness of peer education on changing the
smoking behavior of high schoolage children's. Methods: In this interventional
study; transtheoretical model, which is one of the cognitive-behavioral models
was used for application of the peer education. Study was conducted in Izmir
during 2011-2012 education period and included 338 students from 2 high schools
The independent variable of the study is peer training. Descriptive variables
for a student are age, gender, tendecy of friends to smoke inside and outside the
school, the age they have first experienced the habit, reasons for nicotine
consumption, levels of addiction, chatting about smoking and related harms.
Family descriptive variables are education level of parents and whether their
smoking tendency is present or not. Results: Approximately 18.3% of the students
were current smoker. A positive behavioral change of smoking quitting among
smoker students was observed after peer education. The number of students in
precontemplation stage was reduced while the number of students in stages of
preparation/determination action and maintenance was increased. Conclusion:
Peer education was observed to be an effective method in the behavioral change
of smoking teens. Authors strongly suggest peer education to be one of the
preferred tools in changing the teen behavior in use of tobacco.
PMID- 29332113
TI - Changes in the temporomandibular joint disc and temporal and masseter muscles
secondary to bruxism in Turkish patients.
AB - OBJECTIVES: To analyze the relationships between temporalis and masseter muscle
hypertrophy and temporomandibular joint (TMJ) disc displacement in patients with
severe bruxism using magnetic resonance imaging (MRI). Methods: This
retrospective study included 100 patients with severe bruxism, referred to the
Department of Oral and Maxillofacial Surgery, University of Marmara and Istanbul
Medipol University, Istanbul, Turkey, between January 2015 and December 2016.
Patients underwent TMJ MRI with a 1.5-T system in open and closed mouth
positions. The masseter and temporalis muscles were measured in the axial plane
when the patient's mouth was closed. Results: At its thinnest, the disc averaged
was 1.11+/-0.24 mm. At their thickest, the masseter averaged was 13.65+/-2.19 mm
and temporalis muscles was 12.98+/-2.4 mm. Of the discs, 24% were positioned
normally, 74% were positioned anteriorly, and 2% were positioned posteriorly. The
temporalis muscle was significantly thicker in patients with normally positioned
discs than in those with anteriorly positioned discs (p=0.035). Conclusions: The
temporalis muscle was significantly thicker in patients with normally positioned
discs than in those with anteriorly positioned discs (p=0.035). Additional
studies should be conducted to evaluate the relationships between all masticatory
and surrounding muscles and disc movements in patients with bruxism.
PMID- 29332114
TI - Dental arch dimensions, form and tooth size ratio among a Saudi sample.
AB - OBJECTIVES: To determine the dental arch dimensions and arch forms in a sample of
Saudi orthodontic patients, to investigate the prevalence of Bolton anterior and
overall tooth size discrepancies, and to compare the effect of gender on the
measured parameters. Methods: This study is a biometric analysis of dental casts
of 149 young adults recruited from different orthodontic centers in Jeddah, Saudi
Arabia. The dental arch dimensions were measured. The measured parameters were
arch length, arch width, Bolton's ratio, and arch form. The data were analyzed
using IBM SPSS software version 22.0 (IBM Corporation, New York, USA); this cross
sectional study was conducted between April 2015 and May 2016. Results: Dental
arch measurements, including inter-canine and inter-molar distance, were found to
be significantly greater in males than females (p less than 0.05). The most
prevalent dental arch forms were narrow tapered (50.3%) and narrow ovoid (34.2%),
respectively. The prevalence of tooth size discrepancy in all cases was 43.6% for
anterior ratio and 24.8% for overall ratio. The mean Bolton's anterior ratio in
all malocclusion classes was 79.81%, whereas the mean Bolton's overall ratio was
92.21%. There was no significant difference between males and females regarding
Bolton's ratio. Conclusion: The most prevalent arch form was narrow tapered,
followed by narrow ovoid. Males generally had larger dental arch measurements
than females, and the prevalence of tooth size discrepancy was more in Bolton's
anterior teeth ratio than in overall ratio.
PMID- 29332115
TI - Ultrasound guided transversus abdominis plane block. Postoperative analgesia in
children with spinal dysraphism.
AB - Pediatric regional anesthesia is widely used to relieve postoperative pain after
abdominal surgery. Commonly used techniques of regional anesthesia include lumbar
epidural and caudal block. However, the use of central neuraxial blockade has
limitations. It is contraindicated in patients with clotting abnormalities,
spinal dysraphism with tethered cord syndrome, meningomyelocele, and following
spinal surgery with instrumentation. Ultrasound guided transversus abdominis
plane block is a new method of regional anesthesia that can be used in settings
where central neuraxial blockade is contraindicated. In this study, we present 5
pediatric cases in which major abdominal surgery was performed but central
neuraxial blockade could not be carried out due to spinal abnormalities.
PMID- 29332116
TI - Applying preventive measures leading to significant reduction of catheter
associated urinary tract infections in adult intensive care unit.
AB - OBJECTIVES: To determine the impact of applying the best available clinical
evidence on the preventive measures to reduce the rate of catheter-associated
urinary tract infections (CAUTI) in adult intensive care units (ICU).
Methods: Data were collected from adult ICUs (28 beds) from 2008 to 2016. The
proper use of silicon catheter, aseptic insertion technique, emptying bag three
fourth via close circuit, the use of appropriate size catheter, securing the
draining tube on the thigh to keep catheter bag below patient's bladder level and
removal of the catheter as early as possible were ensured in all patients.
Results: Rate of UTI and urinary catheter utilization ratios were reviewed during
the study period. There was a mean of 6,175 catheter days/year for ICU. Despite
the overall rise in the urinary catheterization ratio over these years; we
observed a significant reduction in the UTI rate per 1000 Urinary catheter days;
from 2.3 in 2010 to 0.3 in 2011 and it was sustained through 2016. Conclusion:
The monthly rates of CAUTI significantly declined after the enforcement of agreed
strategies and interventions to prevent CAUTI rates in adult ICU.
PMID- 29332117
TI - Pseudocholinesterase levels in patients under electroconvulsive therapy.
AB - OBJECTIVES: In this study, we aimed to retrospectively assess the correlation of
pseudocholinesterase (PChE) levels with age, gender, body weight and diagnosed
psychiatric diseases in electroconvulsive therapy (ECT) cases. Methods: This
retrospective study was conducted at Bulent Ecevit University Hospital,
Zonguldak, Turkey, between 2007 and 2011. In the study, 193 ECT case files were
retrospectively scanned to evaluate PChE values before ECT and other file
information. Results: There was no difference between gender in terms of PChE
levels. Correlation analysis determined a weakly positive correlation between age
(p=0.013; correlation coefficient [cc]: 0.178) and body weight (p less than
0.001; cc: 0.273) and PChE levels. No correlation was found between age, gender,
weight or psychiatric diagnosis, and PChE levels. Conclusion: Neuromuscular
blockage is a significant factor that increases patient safety, while increasing
the efficacy of ECT. In choosing muscle relaxant agents, both patient factors and
the pharmacological properties of the neuromuscular blocker should be considered.
We think that in situations with delayed recovery of ECT cases without identified
PChE levels, low PChE levels must be considered.
PMID- 29332118
TI - Primary extraskeletal mesenchymal chondrosarcoma arising from the iliac vein.
AB - [No Abstract Available].
PMID- 29332119
TI - Autofluorescence of Skin Advanced Glycation End Products as a Risk Factor for
Open Angle Glaucoma: The ALIENOR Study.
AB - Purpose: To analyze the association between skin autofluorescence (sAF),
estimating tissue accumulation of advanced glycation end-products (AGEs), and
open angle glaucoma (OAG) in an elderly population. Methods: The Antioxydants,
Lipides Essentiels, Nutrition and maladies OculaiRes (ALIENOR) study is an on
going epidemiologic population-based study on age-related eye diseases. In 2009
to 2010, 624 subjects, aged 74 years or older, were recruited. All subjects
underwent a complete eye examination, including optic disc color photography and
spectral-domain optical coherence tomography (SD-OCT) examination.
Sociodemographic and medical history data were collected using standardized
questionnaires. Glaucoma diagnosis was made using optic nerve head
retinophotography and International Society for Epidemiologic and Geographical
Ophthalmology criteria. sAF was measured with a noninvasive autofluorescence
reader in 467 subjects. Results: Of subjects, 455 had complete data, 424 were
classified as controls, and 31 classified as OAG. Mean age was 82.3 +/- 4.3
years, mean and median sAF were 2.8 +/- 0.7 and 2.7 arbitrary units (AU),
respectively. In a multivariate analysis, higher sAF values (>=2.7 AU) were
associated with OAG (odds ratio [OR] = 2.28, 95% Confidence Interval [CI]: 1.03;
5.04). Other variables significantly associated with OAG were age (OR = 1.10,
95%CI: 1.00; 1.21), glaucoma family history (OR = 2.83, 95%CI: 1.14; 7.01) and
smoking (1-20 pack-years [OR = 3.31, 95%CI: 1.18; 9.26]; >=20 pack-years [OR =
3.85, 95%CI: 1.42; 10.46]). Conclusions: Higher level of sAF, which may act as a
long-term biomarker of metabolic memory, and smoking are independently associated
with an increased risk of glaucoma. Long-term accumulation of AGEs, a marker of
oxidative stress, could play a role in the pathogenesis of glaucomatous chronic
optic neuropathy.
PMID- 29332121
TI - Pattern Onset ERGs and VEPs Produced by Patterns Arising From Light Increment and
Decrement.
AB - Purpose: Our aim was to elaborate how on and off signals contribute to pattern
ERGs and pattern visual evoked potentials (VEPs) by using pedestal patterns
arising from incremental and decremental onset stimulation. Methods: Pattern
onset/offset ERGs and VEPs were produced by black and white checks of 60' side
length and 88% spatial contrast appearing in a 16 degrees field for 200 ms from
white (110 cd/m2), black (7 cd/m2), and gray (48 cd/m2) backgrounds and
disappeared for 1000 ms. Twenty healthy subjects participated in the study
(median age 19.5, range, 5-31 years), 10 of whom also underwent pattern
onset/offset ERG recordings to the same stimuli (median age 25.7, range, 22-31
years). VEPs were recorded from an occipital array referred to Fz. Pattern
electroretinograms (PERGs) were recorded from "Dawson-Trick-Litzkow" (DTL) plus
corneal electrodes referred to ipsilateral outer canthi. Results: There was high
correlation within subjects of the VEP waveform produced by patterns arising from
light increment and decrement (group mean correlation coefficient of PVEPs to
check appearance from black versus white: 87%). An average of increment and
decrement PERGs simulated the onset PERG from a gray background. This waveform is
akin to standard International Society for Clinical Electrophysiology of Vision
(ISCEV) clinical PERGs to reversing checks. Conclusions: In healthy individuals,
the early components of the pattern onset/offset VEP waveforms are comparable to
light increment and decrement pedestal stimulation. Pattern onset/offset ERGs to
pedestal stimulation may be used to probe simultaneous recording of ERGs with
VEPs in order to obtain an assessment of retinal ganglion cell and optic pathway
function in patients with less stable fixation.
PMID- 29332120
TI - Severe Loss of Tritan Color Discrimination in RPE65 Associated Leber Congenital
Amaurosis.
AB - Purpose: RPE65-associated Leber congenital amaurosis (RPE65-LCA) is a progressive
severe retinal dystrophy with early profound dysfunction of rod photoreceptors
followed by progressive cone photoreceptor degeneration. We aim to provide
detailed information about how cone dysfunction affects color discrimination.
Methods: Seven adults (aged 16-21) with RPE65-LCA underwent monocular color
discrimination assessment using the Trivector and Ellipse versions of three
computerized tests: Cambridge Colour Test (CCT), low vision version of the
Cambridge Colour Test (lvvCCT), and the Universal Colour Discrimination Test
(UCDT). For comparison, subjects were also tested using the American Optical
Hardy Rand Rittler (AO-HRR) plates. Each assessment was repeated three times.
Results: The Trivector version of the tests demonstrated that color
discrimination along the tritan axis was undetectable in four subjects, and
severely reduced in three subjects. These findings were confirmed by the Ellipse
version of the tests. Color discrimination along the protan and deutan axes was
evident but reduced in six of seven subjects. Four of seven subjects were unable
to read any of the HRR plates. Conclusions: The computerized color vision tests
adopted in this study provide detailed information about color discrimination in
adult RPE65-LCA patients. The condition is associated with severe impairment of
color discrimination, particularly along the tritan axis indicating possible
early involvement of S-cones, with additional protan and deutan loss to a lesser
extent. This psychophysical assessment strategy is likely to be valuable in
measuring the impact of therapeutic intervention on cone function.
PMID- 29332122
TI - Quantitative Study of the Macular Microvasculature in Human Donor Eyes.
AB - Purpose: To precisely quantify the macular microvasculature density using
microperfusion and labeling techniques in human donor eyes. Such information may
be useful in understanding the role of the macular microvasculature in coping
with the metabolic requirements of the neurons in this densely packed region, and
provide a reference point for clinical studies using recently developed optical
imaging techniques. Methods: The macular microvasculature was perfusion-labeled
in 18 human donor eyes and optical stacks collected from regions superior,
temporal, inferior, and nasal to the foveola using confocal microscopy. The
optical slices were separated into the deep macula vascular layer (DL), and the
superficial layer (SL) in which all the vessels superficial to the deep macular
vessel layer were included. The DL and SL images were analyzed and vessel density
measured according to their orientation from the foveola and in foveal and
parafoveal regions. Vessel densities were compared across regions and age groups.
Results: Both the SL and DL showed an increase in vessel density with increasing
eccentricity from the foveal to parafoveal regions. Vessel density was found to
rank in the order of inferior > superior > temporal > nasal in both SL and DL
layers. The SL vascular density was approximately 31%, whereas DL was
approximately 17%. The DL was planar in nature and density not affected by age.
Age-related increase in vessel density was observed in the SL. Conclusions:
Microperfusion and labeling techniques in combination with confocal microscopy
has enabled collection of reliable data on vascular density in the macula region.
Regional differences may reflect well-matched vascular supply and neuronal
demands. Age-related changes might indicate the importance of stable blood supply
for the human macula.
PMID- 29332123
TI - BRAF, NRAS, and GNAQ Mutations in Conjunctival Melanocytic Nevi.
AB - Purpose: To evaluate BRAF, NRAS, and GNAQ mutations in surgical specimens of
common and blue conjunctival melanocytic nevi. Methods: Surgical specimens from
25 conjunctival melanocytic nevi (23 common and 2 blue) of 25 patients were
evaluated. All common nevi were analyzed immunohistochemically for the expression
of BRAF V600E or NRAS Q61R. One lesion with negative immunoreactivity and for all
blue nevi, a hybridization capture-based next-generation sequencing method was
employed for mutation analysis. For common nevi, genetic features were compared
with clinical and histopathologic findings. Continuous variables (age at excision
and largest basal diameter) were compared with a Students's t-test and all
categoric variables were compared with Fisher's Exact Test. Results: Of common
melanocytic nevi, 9 (39.1%) were immunoreactive for NRASQ61R and 13 (56.5%) were
immunoreactive for BRAFV600E. One common nevus, which was immunonegative for both
BRAFV600E and NRASQ61R was found to harbor an NRASQ61K mutation by sequence
analysis. Patients with NRAS-mutated nevi were more likely to report occurrence
of the lesion prior to 18-years old and more likely to have intrinsic cysts. The
mean largest basal diameter was 6.0 and 3.5 mm for NRAS- and BRAF-immunoreactive
lesions, respectively (P = 0.003). GNAQ mutations were identified in each of the
two blue nevi of this study. Conclusions: These findings document that common
conjunctival melanocytic nevi have mutually exclusive mutations in BRAF and NRAS.
The two conjunctival blue nevi harbored GNAQ mutations. This suggests the driver
mutations of conjunctival nevi are similar to those of nevi of the skin. At the
molecular level, conjunctival nevi appear more like cutaneous nevi than choroidal
nevi.
PMID- 29332124
TI - Optimal Audiovisual Integration in the Ventriloquism Effect But Pervasive
Deficits in Unisensory Spatial Localization in Amblyopia.
AB - Purpose: Classically understood as a deficit in spatial vision, amblyopia is
increasingly recognized to also impair audiovisual multisensory processing.
Studies to date, however, have not determined whether the audiovisual
abnormalities reflect a failure of multisensory integration, or an optimal
strategy in the face of unisensory impairment. We use the ventriloquism effect
and the maximum-likelihood estimation (MLE) model of optimal integration to
investigate integration of audiovisual spatial information in amblyopia. Methods:
Participants with unilateral amblyopia (n = 14; mean age 28.8 years; 7
anisometropic, 3 strabismic, 4 mixed mechanism) and visually normal controls (n =
16, mean age 29.2 years) localized brief unimodal auditory, unimodal visual, and
bimodal (audiovisual) stimuli during binocular viewing using a location
discrimination task. A subset of bimodal trials involved the ventriloquism
effect, an illusion in which auditory and visual stimuli originating from
different locations are perceived as originating from a single location.
Localization precision and bias were determined by psychometric curve fitting,
and the observed parameters were compared with predictions from the MLE model.
Results: Spatial localization precision was significantly reduced in the
amblyopia group compared with the control group for unimodal visual, unimodal
auditory, and bimodal stimuli. Analyses of localization precision and bias for
bimodal stimuli showed no significant deviations from the MLE model in either the
amblyopia group or the control group. Conclusions: Despite pervasive deficits in
localization precision for visual, auditory, and audiovisual stimuli, audiovisual
integration remains intact and optimal in unilateral amblyopia.
PMID- 29332126
TI - Erratum.
PMID- 29332127
TI - Proteome Profiling of Developing Murine Lens Through Mass Spectrometry.
AB - Purpose: We previously completed a comprehensive profile of the mouse lens
transcriptome. Here, we investigate the proteome of the mouse lens through mass
spectrometry-based protein sequencing at the same embryonic and postnatal time
points. Methods: We extracted mouse lenses at embryonic day 15 (E15) and 18 (E18)
and postnatal day 0 (P0), 3 (P3), 6 (P6), and 9 (P9). The lenses from each time
point were preserved in three distinct pools to serve as biological replicates
for each developmental stage. The total cellular protein was extracted from the
lens, digested with trypsin, and labeled with isobaric tandem mass tags (TMT) for
three independent TMT experiments. Results: A total of 5404 proteins were
identified in the mouse ocular lens in at least one TMT set, 4244 in two, and
3155 were present in all three TMT sets. The majority of the proteins exhibited
steady expression at all six developmental time points; nevertheless, we
identified 39 proteins that exhibited an 8-fold differential (higher or lower)
expression during the developmental time course compared to their respective
levels at E15. The lens proteome is composed of diverse proteins that have
distinct biological properties and functional characteristics, including proteins
associated with cataractogenesis and autophagy. Conclusions: We have established
a comprehensive profile of the developing murine lens proteome. This repository
will be helpful in identifying critical components of lens development and
processes essential for the maintenance of its transparency.
PMID- 29332128
TI - Pharmacologic Characterization of Omidenepag Isopropyl, a Novel Selective EP2
Receptor Agonist, as an Ocular Hypotensive Agent.
AB - Purpose: The objective of this study was to investigate the pharmacologic
characteristics of omidenepag isopropyl (OMDI), a compound developed as a novel
intraocular pressure (IOP)-lowering agent, with better IOP control and fewer side
effects than other prostanoid receptor agonists such as prostaglandin F receptor
(FP) agonists. Methods: Binding activities of OMDI and its hydrolyzed form,
omidenepag (OMD), to human recombinant prostanoid receptors (DP1-2, EP1-4, FP,
and IP) were evaluated. Based on these binding assays, the agonistic activities
of OMDI and OMD were further evaluated using cultured cells expressing selected
prostanoid receptors. The pharmacokinetics of OMDI after topical administration
was assessed in rabbits by measurement of the concentrations of both OMDI and OMD
in aqueous humor. The ocular hypotensive effect of OMDI was evaluated in ocular
normotensive rabbits, dogs, and both ocular normotensive and hypertensive
monkeys. Results: OMD was determined to be a selective EP2 receptor agonist. OMDI
weakly bound to EP1; however, the agonistic activity of OMDI to this receptor was
not demonstrated in the functional assay. After topical administration of OMDI,
OMD was detected in aqueous humor whereas OMDI was not detectable. OMDI
significantly lowered IOP in both ocular normotensive and hypertensive animals.
The significant ocular hypotensive effects of OMDI were demonstrated by both
single and repeated dosing, and its effective duration suggests sufficient
efficacy by once-daily dosing. Conclusions: These studies demonstrated that OMDI
is hydrolyzed in the eye to OMD, an EP2 receptor agonist, with a significant
ocular hypotensive effect in both ocular normotensive and hypertensive animal
models.
PMID- 29332125
TI - ICG-001 Exerts Potent Anticancer Activity Against Uveal Melanoma Cells.
AB - Purpose: Uveal melanoma (UM) is uniformly refractory to all available systemic
chemotherapies, thus creating an urgent need for novel therapeutics. In this
study, we investigated the sensitivity of UM cells to ICG-001, a small molecule
reported to suppress the Wnt/beta-catenin-mediated transcriptional program.
Methods: We used a panel of UM cell lines to examine the effects of ICG-001 on
cellular proliferation, migration, and gene expression. In vivo efficacy of ICG
001 was evaluated in a UM xenograft model. Results: ICG-001 exerted strong
antiproliferative activity against UM cells, leading to cell cycle arrest,
apoptosis, and inhibition of migration. Global gene expression profiling revealed
strong suppression of genes associated with cell cycle proliferation, DNA
replication, and G1/S transition. Gene set enrichment analysis revealed that ICG
001 suppressed Wnt, mTOR, and MAPK signaling. Strikingly, ICG-001 suppressed the
expression of genes associated with UM aggressiveness, including CDH1, CITED1,
EMP1, EMP3, SDCBP, and SPARC. Notably, the transcriptomic footprint of ICG-001,
when applied to a UM patient dataset, was associated with better clinical
outcome. Lastly, ICG-001 exerted anticancer activity against a UM tumor xenograft
in mice. Conclusions: Using in vitro and in vivo experiments, we demonstrate that
ICG-001 has strong anticancer activity against UM cells and suppresses
transcriptional programs critical for the cancer cell. Our results suggest that
ICG-001 holds promise and should be examined further as a novel therapeutic agent
for UM.
PMID- 29332129
TI - Aspergillus fumigatus Increased PAR-2 Expression and Elevated Proinflammatory
Cytokines Expression Through the Pathway of PAR-2/ERK1/2 in Cornea.
AB - Purpose: To determine the role of protease-activated receptor-2 (PAR-2) in cornea
infected by Aspergillus fumigatus. Methods: PAR-2 was tested in normal and
infected corneas of C57BL/6 mice. Mice corneas were infected with A. fumigatus
with or without pretreatment of PAR-2 antagonist (FSLLRY-NH2). Polymorphonuclear
neutrophilic leukocytes (PMNs) were stimulated with 75% ethanol-killed A.
fumigatus with or without pretreatment of FSLLRY-NH2. Disease severity was
documented by clinical score and photographs with a slit lamp. PCR, Western blot,
and ELISA tested expression of PAR-2, IL-1beta, TNF-alpha, IFN-gamma, MIP-2, and
p-ERK1/2. PMN infiltration was assessed by myeloperoxidase assay and
immunofluorescent staining. Results: PAR-2 expression was significantly elevated
by A. fumigatus, whereas the upregulation was significantly inhibited by FSLLRY
NH2 in mice corneas. FSLLRY-NH2 decreased disease response, PMN infiltration, and
proinflammatory cytokine expression compared with infected control. In PMNs, PAR
2 expression was also significantly increased by A. fumigatus, which was
significantly inhibited by FSLLRY-NH2. FSLLRY-NH2 significantly inhibited
proinflammatory cytokine protein expression, as compared with that in infected
control cells, which may be modified by p-ERK1/2. Conclusions: These data provide
evidence that A. fumigatus increased PAR-2 expression and elevated disease, PMN
infiltration, and proinflammatory cytokine expression through PAR-2, which may be
modified by p-ERK1/2.
PMID- 29332131
TI - Assessment of Human Corneas Prior to Transplantation Using High-Resolution Two
Photon Imaging.
AB - Purpose: The purpose of this study was to evaluate the feasibility of using two
photon imaging (TPI) to assess the condition of human corneas for
transplantation. Methods: Human corneas were imaged after different storage
times: short-term (STS), medium-term (MTS), and long-term (LTS) storage. A high
resolution, custom-built 5-dimensional multiphoton microscope with 12-fs pulsed
laser excitation was used for image acquisition. Results: Optical discrimination
between different corneal layers and sublayers based on their morphologic
characteristics revealed by two-photon autofluorescence (AF) is possible.
Furthermore, all layers were characterized based on AF lifetimes to gain
information on metabolic activities of cells. The NAD(P)H free to protein-bound
ratio (a1/a2) of epithelial cells increased significantly in both MTS and LTS
corneas compared with STS corneas. In endothelial cells, NAD(P)H a1/a2 was
significantly increased in MTS samples. For keratocytes, the NAD(P)H a1/a2
decreased significantly with storage time. This could indicate that the metabolic
activity of the epithelial and endothelial cells reduces, whereas the activity of
keratocytes increases with storage time. The analysis of the stroma SHG images
indicated that the organization of collagen fibers decreases with storage time.
The feasibility of measuring the endothelial cell density (ECD) using TPI was
demonstrated. An ECD of 1461 +/- 190 cells/mm2 was obtained for MTS samples based
on TPI. Conclusions: TPI can provide information not accessible by current
clinical methods, such as the cells' metabolic state and structural organization
of the stroma, with subcellular resolution. Thus, it may improve the screening
process of corneas prior to transplantation and might help to optimize the
storage conditions.
PMID- 29332132
TI - Reply to Zamani and Hassanian-Moghaddam, 2017: being specific and targeting
disease-causing pathology matter in therapeutics.
PMID- 29332130
TI - Cerebrospinal Fluid Pressure: Revisiting Factors Influencing Optic Nerve Head
Biomechanics.
AB - Purpose: To model the sensitivity of the optic nerve head (ONH) biomechanical
environment to acute variations in IOP, cerebrospinal fluid pressure (CSFP), and
central retinal artery blood pressure (BP). Methods: We extended a previously
published numerical model of the ONH to include 24 factors representing tissue
anatomy and mechanical properties, all three pressures, and constraints on the
optic nerve (CON). A total of 8340 models were studied to predict factor
influences on 98 responses in a two-step process: a fractional factorial
screening analysis to identify the 16 most influential factors, followed by a
response surface methodology to predict factor effects in detail. Results: The
six most influential factors were, in order: IOP, CON, moduli of the sclera,
lamina cribrosa (LC) and dura, and CSFP. IOP and CSFP affected different aspects
of ONH biomechanics. The strongest influence of CSFP, more than twice that of
IOP, was on the rotation of the peripapillary sclera. CSFP had similar influence
on LC stretch and compression to moduli of sclera and LC. On some ONHs, CSFP
caused large retrolamina deformations and subarachnoid expansion. CON had a
strong influence on LC displacement. BP overall influence was 633 times smaller
than that of IOP. Conclusions: Models predict that IOP and CSFP are the top and
sixth most influential factors on ONH biomechanics. Different IOP and CSFP
effects suggest that translaminar pressure difference may not be a good parameter
to predict biomechanics-related glaucomatous neuropathy. CON may drastically
affect the responses relating to gross ONH geometry and should be determined
experimentally.
PMID- 29332134
TI - Breast cancer survivorship: state of the science.
AB - PURPOSE: Only recently has breast cancer survivorship earned formal recognition
as a research discipline. Complicating survivorship research is the frequent
overlap between aging and treatment sequelae. The ACS/ASCO 2016 Breast Cancer
Survivorship Care Guideline (Guideline) reflects comprehensive literature review
through April 2015, while the jointly sponsored, inaugural Cancer Survivorship
Symposium in 2016 (Symposium) reflects ongoing research activity in the area.
Together, these platforms provide an opportunity to examine the use of randomized
trials and controlled studies in survivorship care research. METHODS: All 236
citations from the Guideline and all 250 abstracts from the Symposium were
reviewed independently by two authors and assigned to prospectively determined
categories. RESULTS: Guideline citations were most frequently reviews (n = 88,
37.3%) and non-randomized, non-controlled studies (n = 51, 21.6%). Thirty-seven
(15.7%) randomized trials were cited. Only 9% of Guideline recommendations were
based on randomized clinical trial evidence, while 64% were based on evidence
level "0" (expert opinion, clinical practice, etc.). Symposium abstracts
consisted largely of non-randomized, non-controlled studies (n = 113, 45.2%),
with ten completed randomized trials (4%). Few Guideline citations or Symposium
abstracts incorporated matched, cancer-free controls. CONCLUSIONS: Based on the
literature underlying the ASCO Guideline as well as a survey of the Cancer
Survivorship Symposium abstracts, a significant proportion of the survivorship
literature at least through 2015 consisted of non-randomized, non-controlled
studies. To optimally address survivorship issues, cancer therapy sequelae need
to be distinguished from normal aging in studies incorporating cancer-free
controls, and randomized clinical trials are needed to inform intervention
strategies.
PMID- 29332133
TI - Fumarate hydratase (FH) deficiency in uterine leiomyomas: recognition by
histological features versus blind immunoscreening.
AB - Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is a rare
autosomal dominant disease caused by germline mutations in the fumarate hydratase
(FH) gene. Affected individuals develop cutaneous and uterine leiomyomas and
aggressive RCC. To date, only few publications described the frequency and
morphology of FH-deficient uterine leiomyomas. We reviewed 22 cases collected
over 8 years from routine and consultation files based on distinctive
histological features. In addition, we screened 580 consecutive uterine
leiomyomas from 484 patients, 23 extra-uterine and 8 uterine leiomyosarcomas, and
6 leiomyomas with bizarre nuclei for FH loss using immunohistochemistry (IHC) on
tissue microarrays (TMAs). All 22 FH-deficient cases were suspected on H&E
sections and confirmed by FH IHC. Patients' ages ranged from 25 to 70 years
(median 36). Seventeen patients had multiple nodules (2-14) measuring up to 11.8
cm. None of the patients had stigmata or family history of the HLRCC syndrome.
Histologically, all FH-deficient tumors showed consistent and reproducible
features as reported previously. FH loss was detected in 2/534 evaluable
leiomyomas (0.4%), but in none of leiomyosarcomas. Two of six leiomyomas with
bizarre nuclei were FH-deficient. FH-deficient uterine leiomyomas are rare in
routine material (= 0.4%). They can be reliably identified or suspected by
consistent morphological features. Our data showed predictive morphology to be
superior to blind IHC screening for detecting them. The relationship of FH
deficient uterine smooth muscle tumors to the HLRCC syndrome needs further
clarification.
PMID- 29332136
TI - Consideration of population and cultural factors in American Indian/Alaskan
Native (AIAN) research.
PMID- 29332135
TI - Sequential versus simultaneous use of chemotherapy and gonadotropin-releasing
hormone agonist (GnRHa) among estrogen receptor (ER)-positive premenopausal
breast cancer patients: effects on ovarian function, disease-free survival, and
overall survival.
AB - OBJECTIVE: To investigate ovarian function and therapeutic efficacy among
estrogen receptor (ER)-positive, premenopausal breast cancer patients treated
with gonadotropin-releasing hormone agonist (GnRHa) and chemotherapy
simultaneously or sequentially. METHOD: This study was a phase 3, open-label,
parallel, randomized controlled trial (NCT01712893). Two hundred sixteen
premenopausal patients (under 45 years) diagnosed with invasive ER-positive
breast cancer were enrolled from July 2009 to May 2013 and randomized at a 1:1
ratio to receive (neo)adjuvant chemotherapy combined with sequential or
simultaneous GnRHa treatment. All patients were advised to receive GnRHa for at
least 2 years. The primary outcome was the incidence of early menopause, defined
as amenorrhea lasting longer than 12 months after the last chemotherapy or GnRHa
dose, with postmenopausal or unknown follicle-stimulating hormone and estradiol
levels. The menstrual resumption period and survivals were the secondary
endpoints. RESULT: The median follow-up time was 56.9 months (IQR 49.5-72.4
months). One hundred and eight patients were enrolled in each group. Among them,
92 and 78 patients had complete primary endpoint data in the sequential and
simultaneous groups, respectively. The rates of early menopause were 22.8%
(21/92) in the sequential group and 23.1% (18/78) in the simultaneous group
[simultaneous vs. sequential: OR 1.01 (95% CI 0.50-2.08); p = 0.969; age-adjusted
OR 1.13; (95% CI 0.54-2.37); p = 0.737]. The median menstruation resumption
period was 12.0 (95% CI 9.3-14.7) months and 10.3 (95% CI 8.2-12.4) months for
the sequential and simultaneous groups, respectively [HR 0.83 (95% CI 0.59-1.16);
p = 0.274; age-adjusted HR 0.90 (95%CI 0.64-1.27); p = 0.567]. No significant
differences were evident for disease-free survival (p = 0.290) or overall
survival (p = 0.514) between the two groups. CONCLUSION: For ER-positive
premenopausal patients, the sequential use of GnRHa and chemotherapy showed
ovarian preservation and survival outcomes that were no worse than simultaneous
use. The application of GnRHa can probably be delayed until menstruation
resumption after chemotherapy.
PMID- 29332137
TI - Variation in guideline-concordant care for elderly patients with metastatic
breast cancer in the United States.
AB - PURPOSE: Prior studies have identified shortcomings in the quality of care for
early-stage breast cancer. Guidelines recommend systemic therapy for metastatic
breast cancer (MBC), but few studies have examined guideline concordance for
these patients. METHODS: We used Surveillance, Epidemiology, and End Results
(SEER)-Medicare data to identify patients aged >= 66 diagnosed in 2010-2011 with
de novo MBC who were continuously enrolled in fee-for-service Medicare. We
described initial care (within 6 months of diagnosis) for hormone receptor (HR)
positive/human epidermal receptor-2 (HER2)-negative, HER2-positive, and triple
negative (TN) tumors. We identified factors independently associated with
receiving no initial systemic therapy, and compared hospice and hospital
utilization for treated versus untreated patients. RESULTS: Among 446 patients,
65% were HR-positive, 21% were HER2-positive, and 14% were TN. Most patients
(76.9%) received initial systemic treatment. Among treated HR-positive patients,
15% received chemotherapy as initial treatment; among treated HER2-positive
patients, 34% did not receive HER2-targeted initial therapy. Factors
independently associated with receiving no initial systemic therapy included
older age (ORage continuous/year = 1.08, 95% CI 1.04-1.11), being not married
(ORnot married vs. married = 2.87, 95% CI 1.42-5.81), and subtype (ORTN vs. HR+ =
4.95, 95% CI 2.53-9.71). Of patients who did not receive initial systemic
therapy, 41.1% did not receive hospice services. CONCLUSIONS: In this population
based MBC cohort, almost one quarter did not receive initial systemic therapy and
a substantial proportion of treated patients did not receive guideline-concordant
first-line therapy. Further research should explore underuse of chemotherapy and
HER2-targeted therapies, investigate whether patterns of care are consistent with
patient preferences, and identify opportunities to optimize hospice utilization
for patients not receiving treatment.
PMID- 29332139
TI - Effect of Host Human Products on Natural Transformation in Acinetobacter
baumannii.
AB - Our previous data show that serum albumin can trigger natural transformation in
Acinetobacter baumannii. However, extracellular matrix/basal membrane components,
norepinephrine, and mucin did not have a significant effect on this process.
Therefore, the effect of human products appears to be albumin specific, as both
BSA and HSA have been shown to increase of natural transformation.
PMID- 29332140
TI - Identification of Cross Reactive Antigens of C. botulinum Types A, B, E & F by
Immunoproteomic Approach.
AB - Diseases triggered by microorganisms can be controlled by vaccines, which need
neutralizing antigens. Hence, it is very crucial to identify extremely efficient
immunogens for immune prevention. Botulism, a fatal neuroparalytic disease, is
caused by botulinum neurotoxins produced by the anaerobic, Gram-positive spore
forming bacteria, Clostridium botulinum. Food-borne botulism and iatrogenic
botulism are caused by botulinum toxin. Wound botulism, infant botulism, and
adult intestinal botulism are caused by primarily C. botulinum followed by
secondary intoxication. To identify protective antigens, whole cell proteome of
C. botulinum type B was separated by two-dimensional gel electrophoresis. 2-D gel
of whole cell proteins was probed with hyper immune sera of whole cell proteins
of C. botulinum types A, E, and F. Six cross immunoreactive proteins were
identified. These immunoreactive proteins will be further tested for developing
vaccines and serodiagnostic markers against botulism.
PMID- 29332142
TI - Purification and characterization of a novel organic solvent-tolerant and cold
adapted lipase from Psychrobacter sp. ZY124.
AB - By screening 25 different psychrophilic strains isolated from the Arctic habitat,
we isolated a strain capable of producing lipase. We identified this strain as
Psychrobacter sp. ZY124 based on the amplified 16S rDNA sequence. The lipase,
named as Lipase ZC12, produced from the supernatant of Psychrobacter sp. ZY124
cultured at 15 degrees C was purified to homogeneity by ammonium sulfate
precipitation followed by Phenyl Sepharose FF gel hydrophobic chromatography.
Based on the obtained amino acid sequence, Lipase ZC12 is classified as a member
of the Proteus/psychrophilic subfamily of lipase family I.1; it has a molecular
weight of 37.9 kDa. We also determined that the apparent optimum temperature for
Lipase ZC12 activity is 40 degrees C. Lipase ZC12 shows remarkable organic
solvent tolerance by remaining more 50% after incubated with 10-90% different
organic solvents. In addition, acyl chain esters with C12 or longer were
confirmed to be preferable substrates for Lipase ZC12. Lipase ZC12 also shows
better stereoselectivity for (R, S)-1-phenylethanol chiral resolution in n-hexane
solvent with (S)-1-phenylethanol (eep 92%) and conversion rate (39%) by
transesterification reactions. These properties may provide potential
applications in biocatalysis and biotransformation in non-aqueous media, such as
in detergent, transesterification or esterification and chiral resolution.
PMID- 29332141
TI - Cultivable fungi present in Antarctic soils: taxonomy, phylogeny, diversity, and
bioprospecting of antiparasitic and herbicidal metabolites.
AB - Molecular biology techniques were used to identify 218 fungi from soil samples
collected from four islands of Antarctica. These consisted of 22 taxa of 15
different genera belonging to the Zygomycota, Ascomycota, and Basidiomycota.
Mortierella, Antarctomyces, Pseudogymnoascus, and Penicillium were the most
frequently isolated genera and Penicillium tardochrysogenum, Penicillium
verrucosus, Goffeauzyma gilvescens, and Mortierella sp. 2 the most abundant taxa.
All fungal isolates were cultivated using solid-state fermentation to obtain
their crude extracts. Pseudogymnoascus destructans, Mortierella parvispora, and
Penicillium chrysogenum displayed antiparasitic activities, whilst extracts of P.
destructans, Mortierella amoeboidea, Mortierella sp. 3, and P. tardochrysogenum
showed herbicidal activities. Reported as pathogenic for bats, different isolates
of P. destructans exhibited trypanocidal activities and herbicidal activity, and
may be a source of bioactive molecules to be considered for chemotherapy against
neglected tropical diseases. The abundant presence of P. destructans in soils of
the four islands gives evidence supporting that soils in the Antarctic Peninsula
constitute a natural source of strains of this genus, including some P.
destructans strains that are phylogenetically close to those that infect bats in
North America and Europe/Palearctic Asia.
PMID- 29332138
TI - Pathophysiology of Eosinophilic Esophagitis.
AB - Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus
associated with an atopic predisposition which appears to be increasing in
prevalence over the last few decades. Symptoms stem from fibrosis, swelling, and
smooth muscle dysfunction. In the past two decades, the etiology of EoE has been
and is continuing to be revealed. This review provides an overview of the effects
of genetics, environment, and immune function including discussions that touch on
microbiome, the role of diet, food allergy, and aeroallergy. The review further
concentrates on the pathophysiology of the disease with particular focus on the
important concepts of the molecular etiology of EoE including barrier dysfunction
and allergic hypersensitivity.
PMID- 29332143
TI - Conjunction of G-quadruplex and stem-loop in the 5' untranslated region of mouse
hepatocyte nuclear factor 4-alpha1 mediates strong inhibition of protein
expression.
AB - Hepatocyte nuclear factor 4-alpha (HNF4alpha) is a well-established master
regulator of liver development and function. Restoration of HNF4alpha can treat
multiple liver disorders and liver cancers. To date, HNF4alpha is still
"undruggable" due to lack of known activating ligands. Thus, understanding the
regulatory mechanism of HNF4alpha expression may help develop an alternative
approach to modulate HNF4alpha protein levels. G-quadruplexes (G4) are non
canonical stable secondary structures discovered mostly in the promoters of
oncogenes. Recent genome-wide studies demonstrate the enrichment of G4s in the 5'
untranslated region (UTR). By protoporphyrin IX-binding assay and circular
dichroism spectrum, we validated the presence of a chemically highly stable 4
ring G4 within the 5' UTR of mouse Hnf4a1. Our real-time PCR and Western blot
data showed that the Hnf4a1 5' UTR caused a remarkable translational suppression
regardless of a moderate effect on Hnf4a1 mRNA levels. The subsequent
deletion/mutation analysis of Hnf4a1 5' UTR using dual-luciferase reporter assays
further demonstrated that although the disruption of the chemically highly stable
4-ring G4 resulted in a marked attenuation of inhibition, the G4 alone only
weakly inhibited translation. Likewise, disruption of a long stem-loop adjacent
to the 4-ring G4 markedly attenuated translational inhibition, although the stem
loop alone only exerted a weak inhibitory effect. Thus, the tight conjunction of
G4s and an adjacent stem-loop within the Hnf4a1 5' UTR was both necessary and
sufficient to mediate the very strong translational repression. Our results
establish a novel working model that a chemically stable G4 may require co
factors to be bio-stable for exerting biological functions.
PMID- 29332146
TI - Mercury Concentrations in Northern Two-Lined Salamanders from Stream Ecosystems
in Garrett County, Maryland.
AB - The purpose of this study was to increase our understanding of the
bioaccumulation of mercury in northern two-lined salamanders (Eurycea bislineata
bislineata) in freshwater stream ecosystems. We collected 111 adults and 131
larval northern two-lined salamanders from six streams in Garrett County,
Maryland. These salamanders were collected in April, July, and September 2010. We
measured the size and tissue mercury content in all of these salamanders. We also
measured the total and methyl mercury concentrations in stream water on monthly
basis from April through December 2010. Averaged over all stream ecosystems,
adult northern two-lined salamanders had significantly greater total mercury
concentrations than larval salamanders (29.6 vs. 23.8 ng g-1). For individual
stream ecosystems, the mean tissue mercury contents in adult northern two-lined
salamanders were significantly greater than the mean tissue mercury contents in
larval northern two-lined salamanders for Bear Pen and Mill Run. Adult and larval
salamanders from the Little Savage River and Mud Lick had 1.5-2 times greater
mean tissue mercury contents than salamanders in all other streams. These two
streams also had significantly greater total and methyl mercury concentrations.
Despite their different life-stage feeding behaviors (terrestrial vs. aquatic),
the tissue mercury contents of adult (r = 0.76) and larval (r = 0.79) northern
two-lined salamanders were strongly linked to the methyl mercury concentrations
in stream water. This implies that northern two-lined salamanders may be a useful
bioindicator of mercury pollution in relatively pristine stream ecosystems.
PMID- 29332144
TI - Long-Acting beta2-Agonists in Asthma: Enantioselective Safety Studies are Needed.
AB - Long-acting beta2-agonists (LABAs) such as formoterol and salmeterol are used for
prolonged bronchodilatation in asthma, usually in combination with inhaled
corticosteroids (ICSs). Unexplained paradoxical asthma exacerbations and deaths
have been associated with LABAs, particularly when used without ICS. LABAs
clearly demonstrate effective bronchodilatation and steroid-sparing activity, but
long-term treatment can lead to tolerance of their bronchodilator effects. There
are also concerns with regard to the effects of LABAs on bronchial
hyperresponsiveness (BHR), where long-term use is associated with increased BHR
and loss of bronchoprotection. A complicating factor is that formoterol and
salmeterol are both chiral compounds, usually administered as 50:50 racemic (rac
) mixtures of two enantiomers. The chiral nature of these compounds has been
largely forgotten in the debate regarding LABA safety and effects on BHR,
particularly that (S)-enantiomers of beta2-agonists may be deleterious to asthma
control. LABAs display enantioselective pharmacokinetics and pharmacodynamics.
Biological plausibility of the deleterious effects of beta2-agonists (S)
enantiomers is provided by in vitro and in vivo studies from the short-acting
beta2-agonist (SABA) salbutamol. Supportive clinical findings include the fact
that patients in emergency departments who demonstrate a blunted response to
salbutamol are more likely to benefit from (R)-salbutamol than rac-salbutamol,
and resistance to salbutamol appears to be a contributory mechanism in rapid
asthma deaths. More effort should therefore be applied to investigating potential
enantiospecific effects of LABAs on safety, specifically bronchoprotection.
Safety studies directly assessing the effects of LABA (S)-enantiomers on BHR are
long overdue.
PMID- 29332145
TI - The experiences and beliefs of older people in Scottish very sheltered housing
about using multi-compartment compliance aids.
AB - Background Multi-compartment compliance aids (MCAs) are promoted as a potential
solution to medicines non-adherence despite the absence of high quality evidence
of effectiveness of MCA use impacting medicines adherence or any clinical
outcomes. Furthermore, there is a lack of qualitative research which focuses on
the perspectives of older people receiving MCAs. Objectives To describe
experiences and beliefs surrounding very sheltered housing (VSH) residents' use
of MCAs with emphasis on issues of personalisation, reablement, shared decision
making, independence and support. Setting VSH in north east Scotland. Methods
Qualitative, face-to-face interviews with 20 residents (>= 65 years, using MCA >
6 months) in three VSH complexes. Interviews focused on: when and why the MCA was
first introduced; who was involved in making that decision; how the MCA was used;
perceptions of benefit; and any difficulties encountered. Interviews were
audiorecorded, transcribed and analysed using a framework approach. Main outcome
measure Experiences and beliefs surrounding use of MCAs. Results Nine themes were
identified: shared decision-making; independence; knowledge and awareness of why
MCA had been commenced; support in medicines taking; knowledge and awareness of
medicines; competent and capable to manage medicines; social aspects of carers
supporting MCA use; benefits of MCAs; and drawbacks. Conclusion Experiences and
beliefs are diverse and highly individual, with themes identified aligning to key
strategies and policies of the Scottish Government, and other developed countries
around the world, specifically personalisation shared decision making,
independence, reablement and support.
PMID- 29332147
TI - Phosphorus allocation and phosphatase activity in grasses with different growth
rates.
AB - Different growth rates of grasses from South American natural grasslands are
adaptations to soils of low fertility. Grasses with fast growth rate are species
with an accumulation of nutrients in soluble forms, with a high metabolic rate.
This work aimed to study whether grasses with different growth rates have
different phosphorus (P) uptake and efficiency of P use with high and low P
availability in soil, as well as whether phosphatase activity is related to the
species growth rate and variations in P biochemical forms in the tissues. Three
native grasses (Axonopus affinis, Paspalum notatum, and Andropogon lateralis)
were grown in pots with soil. Along plant growth, biomass production and its
structural components were measured, as well as leaf acid phosphatase activity
and leaf P chemical fractions. At 40 days of growth, leaf acid phosphatase
activity declined by about 20-30% with an increase of P availability in soil for
A. affinis and P. notatum, respectively. Under both soil P levels, P. notatum
showed the highest plant total biomass, leaf dry weight and highest P use
efficiency. A. affinis presented the higher P uptake efficiency and soluble
organic P concentration in the leaf tissues. A. lateralis showed P-Lipid
concentration 1.6 and 1.3 times higher than A. affinis and P. notatum,
respectively. In conclusion, acid phosphatase activity in grass of higher growth
rate is related to higher remobilization of P due to higher demand, as in A.
affinis, and higher growth rates are associated with higher P uptake efficiency.
PMID- 29332151
TI - 1H, 13C and 15N backbone and partial side-chain resonance assignments of the C
terminal domain of HIV-1 Pr55Gag encompassed in NCp15.
AB - During HIV-1 assembly, the Pr55Gag polyprotein precursor (Gag) interacts with the
genomic RNA, with lipids of the plasma membrane, with host proteins (ALIX,
TSG101) through the ESCRT complex, with the viral protein Vpr and are involved in
intermolecular interactions with other Pr55Gag proteins. This network of
interactions is responsible for the formation of the viral particle, the
selection of genomic RNA and the packaging of Vpr. The C-terminal domain of Gag
encompassed in NCp15 is involved in the majority of these interactions, either by
its nucleocapsid or its p6 domains. We study the NCp15 protein as a model of the
C-terminal domain of Gag to better understand the role of this domain in the
assembly and budding of HIV-1. Here, we report the 1H, 13C and 15N chemical shift
assignments of NCp15 obtained by heteronuclear multidimensional NMR spectroscopy
as well as the analysis of its secondary structure in solution. These assignments
of NCp15 pave the way for interaction studies with its numerous partners.
PMID- 29332150
TI - Ectoparasite Activity During Incubation Increases Microbial Growth on Avian Eggs.
AB - While direct detrimental effects of parasites on hosts are relatively well
documented, other more subtle but potentially important effects of parasitism are
yet unexplored. Biological activity of ectoparasites, apart from skin injuries
and blood-feeding, often results in blood remains, or parasite faeces that
accumulate and modify the host environment. In this way, ectoparasite activities
and remains may increase nutrient availability that may favour colonization and
growth of microorganisms including potential pathogens. Here, by the experimental
addition of hematophagous flies (Carnus hemapterus, a common ectoparasite of
birds) to nests of spotless starlings Sturnus unicolor during incubation, we
explore this possible side effect of parasitism which has rarely, if ever, been
investigated. Results show that faeces and blood remains from parasitic flies on
spotless starling eggshells at the end of incubation were more abundant in
experimental than in control nests. Moreover, eggshell bacterial loads of
different groups of cultivable bacteria including potential pathogens, as well as
species richness of bacteria in terms of Operational Taxonomic Units (OTUs), were
also higher in experimental nests. Finally, we also found evidence of a link
between eggshell bacterial loads and increased embryo mortality, which provides
indirect support for a bacterial-mediated negative effect of ectoparasitism on
host offspring. Trans-shell bacterial infection might be one of the main causes
of embryo death and, consequently, this hitherto unnoticed indirect effect of
ectoparasitism might be widespread in nature and could affect our understanding
of ecology and evolution of host-parasite interactions.
PMID- 29332152
TI - Mallory-Weiss syndrome diagnosed after tracheal extubation.
PMID- 29332148
TI - Occurrence of pharmaceuticals and personal care products, and their associated
environmental risks in a large shallow lake in north China.
AB - Eighteen selected pharmaceuticals and personal care products (PPCPs), consisting
of five non-antibiotic pharmaceuticals (N-APs), four sulfonamides (SAs), four
tetracyclines (TCs), four macrolides (MCs), and one quinolone (QN) were detected
in water, pore water, and sediment samples from Baiyangdian Lake, China. A total
of 31 water samples and 29 sediment samples were collected in March 2017.
Caffeine was detected with 100% frequency in surface water, pore water, and
sediment samples. Carbamazepine was detected with 100% frequency in surface water
and sediment samples. Five N-APs were prominent, with mean concentrations of 4.90
266.24 ng/l in surface water and 5.07-14.73 MUg/kg in sediment samples. Four MCs
were prominent, with mean concentrations of 0.97-29.92 ng/l in pore water
samples. The total concentrations of the different classes of PPCPs followed the
order: N-APs (53.26%) > MCs (25.39) > SAs (10.06%) > TCs (7.64%) > QNs (3.64%) in
surface water; N-APs (42.70%) > MCs (25.43%) > TCs (14.69%) > SAs (13.90%) > QNs
(3.24%) in sediment samples, and MCs (42.12%) > N-APs (34.80%) > SAs (11.71%) >
TCs (7.48%) > QNs (3.88%) in pore water samples. The geographical differences of
PPCP concentrations were largely due to anthropogenic activities. Sewage
discharged from Baoding City and human activities around Baiyangdian Lake were
the main sources of PPCPs in the lake. An environmental risk assessment for the
upper quartile concentration was undertaken using calculated risk quotients and
indicated a low or medium-high risk from 18 PPCPs in Baiyangdian Lake and its
five upstream rivers.
PMID- 29332153
TI - Vasoactive-inotropic score as a predictor of morbidity and mortality in adults
after cardiac surgery with cardiopulmonary bypass.
AB - PURPOSE: The vasoactive-inotropic score (VIS) is a scale showing the amount of
vasoactive and inotropic support. Recently, it was suggested that the VIS after
cardiac surgery predicts morbidity and mortality in infants. The purpose of this
study was to evaluate the VIS at the end of surgery as a predictor of morbidity
and mortality in adult cardiac surgery. METHODS: A retrospective cohort study of
129 adult cardiac surgery patients was performed at a university hospital. The
primary outcome was termed "poor outcome", which was a composite of morbidity and
mortality. The secondary outcomes were the duration of intensive care unit (ICU)
stay and time to first extubation. Multivariate logistic regression analysis was
performed to evaluate the association between the VIS and poor outcomes. A
proportional hazards model was used to evaluate the duration of the ICU stay and
time to first extubation. RESULTS: After adjusting for the EuroSCORE,
preoperative ejection fraction, and bypass time, a high VIS at the end of surgery
was associated with a poor outcome with an adjusted odds ratio of 4.87 (95%
confidence interval 1.51-18.94; p = 0.007). After controlling for the EuroSCORE
and bypass time, patients with a high VIS experienced longer ICU stay (hazard
ratio 1.62; 95% confidence interval 1.10-2.39; p = 0.015) and needed longer
ventilation (hazard ration 1.87; 95% confidence interval 1.28-2.74, p = 0.001).
CONCLUSIONS: The amount of cardiovascular support at the end of cardiac surgery
may predict morbidity and mortality in adults.
PMID- 29332154
TI - The influence of systemically or locally administered mesenchymal stem cells on
tissue repair in a rat oral implantation model.
AB - BACKGROUND: Multipotent mesenchymal stem cells (MSCs) are used clinically in
regenerative medicine. Our previous report showed systemically injected MSCs
improved peri-implant sealing and accelerated tissue healing. However, the risks
of systemic MSC administration, including lung embolism, must be considered;
therefore, their local application must be assessed for clinical safety and
efficacy. We investigated differences in treatment effect between local and
systemic MSC application using a rat oral implantation model. METHODS: Rat bone
marrow-derived MSCs were isolated and culture-expanded. The rat's right maxillary
first molars were extracted and replaced with experimental titanium implants.
After 24 h, MSCs (1 * 106/ml) were systemically or locally injected into
recipient rats via the tail vein (systemic group) or buccal subcutaneous tissue
(local group), respectively. Rats treated in the absence of MSCs were included as
a control (control group). The maxillary epithelium was assessed histologically
after 4 weeks to evaluate laminin-332 (Ln-332) distribution and horseradish
peroxidase invasion, as indicators of peri-implant epithelium (PIE) formation and
PIE sealing to the implant surface, respectively. The effect of MSCs on rat oral
epithelial cell (OEC) morphology was determined by coculture. RESULTS: Systemic
group MSCs accumulated early at the peri-implant mucosa, while local group MSCs
were observed in various organs prior to later accumulation around the implant
surface. PIE formation and Ln-332-positive staining at the implant interface were
enhanced in the systemic group compared with the local and control groups.
Furthermore, OEC adherence on implants was reduced in high-density compared with
low-density MSC cocultures. CONCLUSIONS: Local MSC injection was more ineffective
than systemic MSC injection at enhancing PIE sealing around titanium implants.
Thus, although local MSC administration has a wide range of applications, further
investigations are needed to understand the exact cellular and molecular
mechanisms of this approach prior to clinical use.
PMID- 29332155
TI - Prevalence of the Pfdhfr and Pfdhps mutations among asymptomatic pregnant women
in Southeast Nigeria.
AB - Sulfadoxine-pyrimethamine (SP) is the recommended drug for intermittent
preventive treatment of malaria in pregnancy in most of sub-Saharan Africa.
Resistance to SP is related to mutations in the dhfr and dhps gene of Plasmodium
falciparum. This study determined the prevalence of Pfdhfr and Pfdhps
polymorphisms found in asymptomatic pregnant women attending antenatal care in
Calabar, Nigeria. From October 2013 to November 2014, asymptomatic pregnant women
attending antenatal care clinics were enrolled after obtaining informed consent.
Malaria diagnosis testing was done using thick and thin smears. Dried blood spot
filter papers were collected. Parasite DNA was extracted from the filter papers
using a chelex extraction. Extraction was followed by nested PCR and restriction
enzyme digestion. P. falciparum infection was detected by microscopy in 7%
(32/459) participants. Twenty-eight P. falciparum isolates were successfully
genotyped. In the Pfdhfr gene, the triple mutation was almost fixed; S108N
mutation was (100%), N51I (93%) and C59R mutations (93%), whereas the I164L
mutation was absent. The prevalence of Pfdhps S436A, A437G, A581G and A613S
mutations was 82.1% (23/28), 96.4% (27/28), 71.4% (20/28) and 71.4% (20/28)
respectively. The K540E mutation was absent. The prevalence of the Pfdhfr triple
mutation IRNI was 92.9% (26/28). The efficacy of SP as IPTp in Southeast Nigeria
may be severely threatened. The continuous monitoring of SP molecular markers of
resistance is required to assess thresholds. The evaluation of alternative
preventive treatment strategies and drug options for preventing malaria in
pregnancy may be necessary.
PMID- 29332156
TI - Enterocytozoon bieneusi genotypes in Tibetan sheep and yaks.
AB - Few studies have been conducted on the distribution of Enterocytozoon bieneusi
genotypes in Tibetan sheep and yaks, which live outdoors in extreme climate with
high altitude. In this study, fecal specimens from 312 Tibetan sheep and 554 yaks
in Qinghai, China, were collected and examined for E. bieneusi by PCR-sequence
analysis of the ribosomal internal transcribed spacer. Among them, 73 (23.4%)
specimens from Tibetan sheep and 40 (7.2%) from yaks were positive for E.
bieneusi. There were eight E. bieneusi genotypes in Tibetan sheep, including
three known ones (BEB6, COS-I, and NESH5) and five novel ones (named as CHS13
CHS17). Similarly, seven E. bieneusi genotypes were found in yaks, including five
known ones (J, BEB4, BEB6, COS-I, and NESH5) and two novel ones (named as CHN13
and CHN14). Most of the E. bieneusi genotypes and all frequent ones identified in
the study belonged to group 2. One new subgroup of genotypes was identified
within group 1. The distribution of E. bieneusi genotypes was different between
Tibetan sheep and yaks, with BEB6 as the dominant one (42.5%) in Tibetan sheep
and J as the dominant one (47.5%) in yaks. These data support the occurrence of
host adaptation among E. bieneusi genotypes within group 2.
PMID- 29332157
TI - Acanthamoeba keratitis in Porto Alegre (southern Brazil): 28 cases and risk
factors.
AB - The increasing use of contact lenses worldwide has led to an increase in cases of
Acanthamoeba keratitis, which are often associated with inappropriate cleaning of
contact lenses and lens cases. This study aimed to retrospectively review 28
cases of Acanthamoeba keratitis in Porto Alegre (southern Brazil) and identify
the risk factors and clinical outcomes of affected patients. Most patients had
higher education (66.6%), all were users of contact lenses, mostly women (67.9%).
Most patients were soft contact lens wearers (66.7%) and 85.7% used multipurpose
cleaning solutions. Sixteen patients (64.0%) used to wear contact lenses while
swimming and/or bathing. Pain was the most common symptom (92.6%). For treatment,
patients used polyhexamethylene biguanide drops (92.6%), propamidine isethionate
drops (81.5%), chlorhexidine drops (55.6%), topical corticosteroids (63.0%), and
systemic corticosteroids (37.0%). Herpes simplex keratitis was the most common
misdiagnosis (72.7%). The majority of patients (76.0%) underwent a corneal
transplant to control the disease.
PMID- 29332158
TI - Combined sublethal irradiation and agonist anti-CD40 enhance donor T cell
accumulation and control of autochthonous murine pancreatic tumors.
AB - Tumor-reactive T lymphocytes can promote the regression of established tumors.
However, their efficacy is often limited by immunosuppressive mechanisms that
block T cell accumulation or function. ACT provides the opportunity to ameliorate
immune suppression prior to transfer of tumor-reactive T cells to improve the
therapeutic benefit. We evaluated the combination of lymphodepleting whole body
irradiation (WBI) and agonist anti-CD40 (alphaCD40) antibody on control of
established autochthonous murine neuroendocrine pancreatic tumors following the
transfer of naive tumor-specific CD8 T cells. Sublethal WBI had little impact on
disease outcome but did promote T cell persistence in the lymphoid organs. Host
conditioning with alphaCD40, an approach known to enhance APC function and T cell
expansion, transiently increased donor T cell accumulation in the lymphoid organs
and pancreas, but failed to control tumor progression. In contrast, combined WBI
and alphaCD40 prolonged T cell proliferation and dramatically enhanced
accumulation of donor T cells in both the lymphoid organs and pancreas. This dual
conditioning approach also promoted high levels of inflammation in the pancreas
and tumor, induced histological regression of established tumors, and extended
the lifespan of treated mice. Prolonged survival was entirely dependent upon
adoptive transfer, but only partially dependent upon IFNgamma production by donor
T cells. Our results identify the novel combination of two clinically relevant
host conditioning approaches that synergize to overcome immune suppression and
drive strong tumor-specific T cell accumulation within well-established tumors.
PMID- 29332160
TI - Determination of the Critical Micelle Concentration of Neutral and Ionic
Surfactants with Fluorometry, Conductometry, and Surface Tension-A Method
Comparison.
AB - Micelles are of increasing importance as versatile carriers for hydrophobic
substances and nanoprobes for a wide range of pharmaceutical, diagnostic,
medical, and therapeutic applications. A key parameter indicating the formation
and stability of micelles is the critical micelle concentration (CMC). In this
respect, we determined the CMC of common anionic, cationic, and non-ionic
surfactants fluorometrically using different fluorescent probes and fluorescence
parameters for signal detection and compared the results with conductometric and
surface tension measurements. Based upon these results, requirements, advantages,
and pitfalls of each method are discussed. Our study underlines the versatility
of fluorometric methods that do not impose specific requirements on surfactants
and are especially suited for the quantification of very low CMC values.
Conductivity and surface tension measurements yield smaller uncertainties
particularly for high CMC values, yet are more time- and substance consuming and
not suitable for every surfactant.
PMID- 29332162
TI - Roles of Irisin in the Linkage from Muscle to Bone During Mechanical Unloading in
Mice.
AB - Mechanical unloading induces disuse muscle atrophy and bone loss, but the details
in mechanism involved in those pathophysiological conditions are not fully
understood. Interaction between muscle and bone has been recently noted. Here, we
investigated the roles of humoral factors linking muscle to bone during
mechanical unloading using mice with hindlimb unloading (HU) and sciatic
neurectomy (SNX). HU and SNX reduced muscle volume surrounding the tibia, tissue
weights of soleus and gastrocnemius muscle, and trabecular bone mineral density
(BMD) in the tibia of mice. Among humoral factors linking muscle to bone, HU and
SNX reduced fibronectin type III domain-containing 5 (FNDC5) mRNA levels in the
soleus muscle of mice. Simple regression analysis revealed that FNDC5 mRNA levels
in the soleus muscle were positively related to trabecular BMD in the tibia of
control and HU mice as well as sham and SNX mice. Moreover, FNDC5 mRNA levels
were negatively correlated with receptor activator of nuclear factor-kappaB
ligand (RANKL) mRNA levels in the tibia of control and HU mice. Irisin, a product
of FNDC5, suppressed osteoclast formation from mouse bone marrow cells and RANKL
mRNA levels in primary osteoblasts. FNDC5 mRNA levels elevated by fluid shear
stress were antagonized by bone morphogenetic protein (BMP) and
phosphatidylinositol 3-kinase (PI3K) signaling inhibitors in myoblastic C2C12
cells. In conclusion, the present study first showed that mechanical unloading
reduces irisin expression in the skeletal muscle of mice presumably through BMP
and PI3K pathways. Irisin might be involved in muscle/bone relationships
regulated by mechanical stress in mice.
PMID- 29332161
TI - The computed tomography adrenal wash-out analysis properly classifies cortisol
secreting adrenocortical adenomas.
AB - PURPOSE: Adrenocortical lesions are characterized through imaging, hormonal and
histopathological analysis. Our aim was to compare the radiological features of
adrenocortical lesions with their cortisol-secreting status and histopathological
Weiss score. METHODS: Seventy five patients operated between 2004 and 2016 in the
University Hospital of Nancy for either adrenocortical carcinomas (ACC) or
adrenocortical adenomas (ACA) were enrolled in this study. We collected cortisol
parameters, Computed Tomography (CT) scans (unenhanced density, wash-out (WO)
analysis) and 18F-Fluorodeoxyglucose positron emission tomography/computed
tomography (18F-FDG PET/CT) datas. The histopathological Weiss score ultimately
differentiates ACA (score <= 2) from ACC (score >= 3). One-way ANOVA, Fisher's
exact and unpaired t tests were used for statistical analysis with significancy
reached at p < 0.05. RESULTS: There were 23 ACC and 52 ACA with 40 patients (53%)
who had an autonomous secretion of cortisol. On CT scan, ACC were larger compared
to ACA (108 vs. 37 mm, p < 0.0001). A roughly similar proportion of cortisol
secreting (22/25) and non-secreting (15/19) ACA were atypical (i.e., unenhanced
density value >= 10 Hounsfield Units [HU]), however 85% of cortisol-secreting vs.
40% of non-secreting ACA were classified as benigns by the relative WO analysis
(p = 0.08). Likewise, there was a trend for a higher 18F-FDG uptake in cortisol
secreting ACA compared to non-secreting ACA (p = 0.053). CONCLUSIONS: The
relative adrenal WO analysis consolidates the benign nature of an ACA, especially
in case of cortisol oversecretion, a condition known to compromise the diagnostic
accuracy of the 10 HU unenhanced CT attenuation threshold.
PMID- 29332163
TI - The monkey is not always a God: Attitudinal differences toward crop-raiding
macaques and why it matters for conflict mitigation.
AB - Attitudinal differences toward wildlife have important implications for conflict
management and when the species in question have strong cultural and religious
associations, conflict mitigation becomes a challenging endeavor. We investigated
farmers' attitudes toward two different crop-raiding macaque species, the rhesus
macaque in northern India, and the bonnet macaque in southern India. Apart from
regional differences in attitudes, we also assessed temporal changes in attitude
toward the rhesus macaque. We carried out household surveys using a
semistructured questionnaire to collect data. Our findings reveal that
respondents in southern and northern India differ significantly in their views
regarding species sanctity and preference for mitigation options. Although
people's perceptions of the rhesus macaques had changed over time in northern
India, farmers were still unwilling to cause harm to the macaques. We discuss the
underlying causes of these observed differences in attitude and their impact on
the management of human-macaque conflict.
PMID- 29332159
TI - Transposable elements: genome innovation, chromosome diversity, and centromere
conflict.
AB - Although it was nearly 70 years ago when transposable elements (TEs) were first
discovered "jumping" from one genomic location to another, TEs are now recognized
as contributors to genomic innovations as well as genome instability across a
wide variety of species. In this review, we illustrate the ways in which active
TEs, specifically retroelements, can create novel chromosome rearrangements and
impact gene expression, leading to disease in some cases and species-specific
diversity in others. We explore the ways in which eukaryotic genomes have evolved
defense mechanisms to temper TE activity and the ways in which TEs continue to
influence genome structure despite being rendered transpositionally inactive.
Finally, we focus on the role of TEs in the establishment, maintenance, and
stabilization of critical, yet rapidly evolving, chromosome features: eukaryotic
centromeres. Across centromeres, specific types of TEs participate in genomic
conflict, a balancing act wherein they are actively inserting into centromeric
domains yet are harnessed for the recruitment of centromeric histones and
potentially new centromere formation.
PMID- 29332164
TI - Skewing of the genetic architecture at the ZMYM3 human-specific 5' UTR short
tandem repeat in schizophrenia.
AB - Differential expansion of a number of human short tandem repeats (STRs) at the
critical core promoter and 5' untranslated region (UTR) support the hypothesis
that at least some of these STRs may provide a selective advantage in human
evolution. Following a genome-wide screen of all human protein-coding gene 5'
UTRs based on the Ensembl database ( http://www.ensembl.org ), we previously
reported that the longest STR in this interval is a (GA)32, which belongs to the
X-linked zinc finger MYM-type containing 3 (ZMYM3) gene. In the present study, we
analyzed the evolutionary implication of this region across evolution and
examined the allele and genotype distribution of the "exceptionally long" STR by
direct sequencing of 486 Iranian unrelated male subjects consisting of 196 cases
of schizophrenia (SCZ) and 290 controls. We found that the ZMYM3 transcript
containing the STR is human-specific (ENST00000373998.5). A significant allele
variance difference was observed between the cases and controls (Levene's test
for equality of variances F = 4.00, p < 0.03). In addition, six alleles were
observed in the SCZ patients that were not detected in the control group
("disease-only" alleles) (mid p exact < 0.0003). Those alleles were at the
extreme short and long ends of the allele distribution curve and composed 4% of
the genotypes in the SCZ group. In conclusion, we found skewing of the genetic
architecture at the ZMYM3 STR in SCZ. Further, we found a bell-shaped
distribution of alleles and selection against alleles at the extreme ends of this
STR. The ZMYM3 STR sets a prototype, the evolutionary course of which determines
the range of alleles in a particular species. Extreme "disease-only" alleles and
genotypes may change our perspective of adaptive evolution and complex disorders.
The ZMYM3 gene "exceptionally long" STR should be sequenced in SCZ and other
human-specific phenotypes/characteristics.
PMID- 29332165
TI - Factors Associated with Anxiety About Colonoscopy: The Preparation, the
Procedure, and the Anticipated Findings.
AB - BACKGROUND: Previous research has assessed anxiety around colonoscopy procedures,
but has not considered anxiety related to different aspects related to the
colonoscopy process. AIMS: Before colonoscopy, we assessed anxiety about: bowel
preparation, the procedure, and the anticipated results. We evaluated
associations between patient characteristics and anxiety in each area. METHODS:
An anonymous survey was distributed to patients immediately prior to their
outpatient colonoscopy in six hospitals and two ambulatory care centers in
Winnipeg, Canada. Anxiety was assessed using a visual analog scale. For each
aspect, logistic regression models were used to explore associations between
patient characteristics and high anxiety. RESULTS: A total of 1316 respondents
completed the questions about anxiety (52% female, median age 56 years). Anxiety
scores > 70 (high anxiety) were reported by 18% about bowel preparation, 29%
about the procedure, and 28% about the procedure results. High anxiety about
bowel preparation was associated with female sex, perceived unclear instructions,
unfinished laxative, and no previous colonoscopies. High anxiety about the
procedure was associated with female sex, no previous colonoscopies, and
confusing instructions. High anxiety about the results was associated with
symptoms as an indication for colonoscopy and instructions perceived as
confusing. CONCLUSIONS: Fewer people had high anxiety about preparation than
about the procedure and findings of the procedure. There are unique predictors of
anxiety about each colonoscopy aspect. Understanding the nuanced differences in
aspects of anxiety may help to design strategies to reduce anxiety, leading to
improved acceptance of the procedure, compliance with preparation instructions,
and less discomfort with the procedure.
PMID- 29332166
TI - Imaging in juvenile idiopathic arthritis - international initiatives and ongoing
work.
AB - Imaging is increasingly being integrated into clinical practice to improve
diagnosis, disease control and outcome in children with juvenile idiopathic
arthritis. Over the last decades several international groups have been launched
to standardize and validate different imaging techniques. To enhance transparency
and facilitate collaboration, we present an overview of ongoing initiatives.
PMID- 29332168
TI - Efficient CRISPR/Cas9-based genome editing in carrot cells.
AB - KEY MESSAGE: The first report presenting successful and efficient carrot genome
editing using CRISPR/Cas9 system. Clustered Regularly Interspaced Short
Palindromic Repeats (CRISPR)/CRISPR-associated (Cas9) is a powerful genome
editing tool that has been widely adopted in model organisms recently, but has
not been used in carrot-a model species for in vitro culture studies and an
important health-promoting crop grown worldwide. In this study, for the first
time, we report application of the CRISPR/Cas9 system for efficient targeted
mutagenesis of the carrot genome. Multiplexing CRISPR/Cas9 vectors expressing two
single-guide RNA (gRNAs) targeting the carrot flavanone-3-hydroxylase (F3H) gene
were tested for blockage of the anthocyanin biosynthesis in a model purple
colored callus using Agrobacterium-mediated genetic transformation. This approach
allowed fast and visual comparison of three codon-optimized Cas9 genes and
revealed that the most efficient one in generating F3H mutants was the
Arabidopsis codon-optimized AteCas9 gene with up to 90% efficiency. Knockout of
F3H gene resulted in the discoloration of calli, validating the functional role
of this gene in the anthocyanin biosynthesis in carrot as well as providing a
visual marker for screening successfully edited events. Most resulting mutations
were small Indels, but long chromosome fragment deletions of 116-119 nt were also
generated with simultaneous cleavage mediated by two gRNAs. The results
demonstrate successful site-directed mutagenesis in carrot with CRISPR/Cas9 and
the usefulness of a model callus culture to validate genome editing systems.
Given that the carrot genome has been sequenced recently, our timely study sheds
light on the promising application of genome editing tools for boosting basic and
translational research in this important vegetable crop.
PMID- 29332169
TI - Measuring cochlear duct length in Asian population: worth giving a thought!
AB - INTRODUCTION: The anatomy of the cochlea forms the basis for a successful
cochlear implantation. Cochlear duct length (CDL) is defined as the length of the
scala media as measured from the middle of the round window to helicotrema.
Preoperative measurement of CDL is particularly important when precise
intracochlear electrode array placement is desired. It can be done both
histologically and radiologically. Preoperative high-resolution computed
tomography (HRCT) scan which forms an integral part of cochlear implant workup is
a useful tool to calculate CDL using 3D reconstructions. METHOD: This study was
done in SMS Medical College and Hospital, Jaipur, India, which is a tertiary care
hospital and referral centre for cochlear implants. HRCT temporal bones of all
children less than 6 years of age, with congenital bilateral severe-to-profound
SNHL who were being worked up for cochlear implant were studied and analysed. 124
patients (56 females and 68 males) with hearing loss were evaluated for cochlear
implantation. HRCT temporal bone of these patients was analysed and a variable A
was measured which is defined as the linear measurement from the round window to
the farthest point on the opposite wall of the cochlea on a reformatted CT scan
slice. RESULTS: Mean of distance A for right ear of these patients was 8.10 mm
(range 7.7-9.2 mm). Mean for the same in left ear of these patients was 8.14 mm
(range 7.7-9.0 mm), giving an overall average of 8.12 mm. Using the formula, CDL
= 4.16A-3.98, we calculated the length of cochlear duct. Mean cochlear duct
length was 29.8 mm with a range from 28 to 34.3 mm. CONCLUSION: To the best of
our knowledge, this is the first large sample study of cochlear length in
population of this part of the world. A smaller cochlear length in this part of
the world as compared to the Caucasian cochlear duct is a significant finding in
understanding of the cochlear anatomy and physiology. It would also have great
implications on the insertion depth in cochlear implantation.
PMID- 29332170
TI - MiRNA-mRNA crosstalk in laryngeal squamous cell carcinoma based on the TCGA
database.
AB - BACKGROUND: The functional characterization of non-coding microRNAs (miRNAs) has
been shown to be associated with the pathophysiology of the disease, but it is
still a challenging task to elucidate the pathogenesis of microRNAs and disease.
In addition, the understanding of the role of miRNAs in the development of LSCC
still needs further exploration. MATERIALS AND METHODS: In this study, to
identify miRNAs that play a key role in LSCC, we analyzed miRNA and mRNA sequence
data from 162 LSCC samples from the TCGA database, and screened specific miRNAs
and mRNAs by differential gene expression analysis. And then, construct a
differentially expressed miRNAs and mRNAs interaction network. RESULTS: In our
investigation, 23 miRNAs (P < 0.01, log2FoldChange > 2) and 331 mRNAs (P < 0.01,
log2FoldChange > 4) were identified differentially expressed in LSCC and reduced
the number of loosely linked miRNAs and mRNAs according to appropriate
thresholds. Finally, 13 miRNAs and 35 mRNAs were enriched in a network.
CONCLUSIONS: Our study provides the most comprehensive information on the
expression of miRNAs in LSCC and identifies the known oncogenic miRNAs (such as
miR-163a), as well as aberrant expression of novel miRNAs involved in cell
regulation and metabolic defects that occur during development of LSCC.
PMID- 29332167
TI - Non-coding RNAs and plant male sterility: current knowledge and future prospects.
AB - KEY MESSAGE: Latest outcomes assign functional role to non-coding (nc) RNA
molecules in regulatory networks that confer male sterility to plants. Male
sterility in plants offers great opportunity for improving crop performance
through application of hybrid technology. In this respect, cytoplasmic male
sterility (CMS) and sterility induced by photoperiod (PGMS)/temperature (TGMS)
have greatly facilitated development of high-yielding hybrids in crops.
Participation of non-coding (nc) RNA molecules in plant reproductive development
is increasingly becoming evident. Recent breakthroughs in rice definitively
associate ncRNAs with PGMS and TGMS. In case of CMS, the exact mechanism through
which the mitochondrial ORFs exert influence on the development of male
gametophyte remains obscure in several crops. High-throughput sequencing has
enabled genome-wide discovery and validation of these regulatory molecules and
their target genes, describing their potential roles performed in relation to
CMS. Discovery of ncRNA localized in plant mtDNA with its possible implication in
CMS induction is intriguing in this respect. Still, conclusive evidences linking
ncRNA with CMS phenotypes are currently unavailable, demanding complementing
genetic approaches like transgenics to substantiate the preliminary findings.
Here, we review the recent literature on the contribution of ncRNAs in conferring
male sterility to plants, with an emphasis on microRNAs. Also, we present a
perspective on improved understanding about ncRNA-mediated regulatory pathways
that control male sterility in plants. A refined understanding of plant male
sterility would strengthen crop hybrid industry to deliver hybrids with improved
performance.
PMID- 29332171
TI - Long-term patient-related outcome measures of septoplasty: a systematic review.
AB - PURPOSE: Septoplasty is a common rhinological procedure intended to relieve
symptoms of chronic nasal obstruction. However, there remains a question as to
whether patients obtain symptom improvement and are satisfied with surgical
outcomes in the months and years after septoplasty. This review aims to evaluate
the long-term efficacy of functional septoplasty for nasal septal deviation.
METHODS: A systematic review of the literature was conducted from November 2014
to March 2016 using the Cochrane, EMBASE, and PubMed databases. Prospective
trials concerning functional septoplasty, which assessed subjective outcomes and
included long-term follow-up data (>= 9 month post-septoplasty) were included.
RESULTS: 2189 articles were screened with seven meeting the criteria for
inclusion. Patient satisfaction was assessed in six studies, with rates of
satisfaction provided in three of these, ranging from 69 to 100%. Two studies
assessed the degree of patient satisfaction, with one study indicating that 88%
of patients were moderately satisfied or better at 1 year post-op, and the other
reporting that 50% of patients were satisfied. In assessing symptom relief,
several methods were used, including validated questionnaires, with varying
degrees of improvement in nasal obstruction reported. CONCLUSIONS: Septoplasty
appears to be a far from perfect treatment for nasal obstruction due to septal
deviation. However, given the heterogeneity of data and lack of randomized
controlled trials (RCTs), future RCTs and use of validated questionnaires would
enable generation of superior levels of evidence. We suggest future prospective
trials evaluating prognostic factors in septoplasty, to better inform patients
and facilitate the development of guidelines for surgical intervention.
PMID- 29332172
TI - Spirituality as a protective health asset for young people: an international
comparative analysis from three countries.
AB - OBJECTIVES: Spirituality has been proposed as a potential health asset a
'developmental engine' that works by fostering the search for connectedness,
meaning and purpose. The aim is to examine to what extent spiritual health might
be protective of young people's overall health and well-being. METHODS: In 2014,
young people aged 11, 13, and 15 years in England, Scotland and Canada were
surveyed as part of the HBSC study (n = 26,701). The perceived importance of
spiritual health and domains (connections with self, others, nature, and the
transcendent) was measured in these countries. Multi-level log-binomial models
were used to explore relationships between spiritual health and three self
reported positive health outcomes: general health status, subjective life
satisfaction and health complaints. RESULTS: Higher levels of perceptions of the
importance of spiritual health, both overall and within the four domains, were
associated with higher likelihoods of reporting each of the positive health
outcomes. CONCLUSIONS: Spiritual health appears to operate as a protective health
asset during adolescence and is significantly shaped by external relationships
and connections.
PMID- 29332174
TI - A friend in knee: CCN3 may inhibit osteoarthritis progression.
AB - Osteoarthritis (OA) is a major clinical problem among the ageing population, yet
no disease-modifying treatments currently exist. This issue arises, in part, due
to the complex processes occurring in the microenvironment of articular cartilage
that lead to osteoarthritic changes. Gaining a better understanding of these
processes is crucial in developing a viable therapy for OA. A recent report in
Journal of Bone Mineral Metabolism by Janune et al. (J Bone Miner Metab 35:582
597, 2016) suggests a novel role for CCN3 in maintaining the differentiated
phenotype of articular cartilage. This report suggests that CCN3, a member of the
CCN family of matricellular proteins, is important for proteoglycan accumulation,
as well as expression of type II collagen, tenascin C, and lubricin in vitro.
Furthermore, exogenous CCN3 increased tidemark integrity and lubricin protein
expression in a rat model of OA. These results implicate the regulation of CCN3
as a potential therapeutic target in patients with OA.
PMID- 29332173
TI - Is the use of emergency departments socially patterned?
AB - OBJECTIVES: To analyse the association between patients' socioeconomic position
(SEP) and the use of emergency departments (EDs). METHODS: This population-based
study included all visits to ED in 2012 by inhabitants of the French Midi
Pyrenees region, recorded by the Regional Emergency Departments Observatory. We
compared ED visit rates and the proportion of non-severe visits according to the
patients' SEP as assessed by the European Deprivation Index. RESULTS: We analysed
496,388 visits. The annual ED visit rate increased with deprivation level: 165.9
[95% CI (164.8-166.9)] visits per 1000 inhabitants among the most advantaged
group, compared to 321.9 [95% CI (320.3-323.5)] per 1000 among the most
disadvantaged. However, the proportion of non-severe visits was about 14% of the
visits, and this proportion did not differ according to SEP. CONCLUSIONS:
Although the study shows a difference of ED visit rates, the probability of a
visit being non-severe is not meaningfully different according to SEP. This
supports the assumption that ED visit rate variations according to SEP are mainly
explained by SEP-related differences in health states rather than SEP-related
differences in health behaviours.
PMID- 29332175
TI - Breast cancer survivor's perspectives on the role different providers play in
follow-up care.
AB - IMPORTANCE: Significant variation in the number and types of oncologists that
provide breast cancer follow-up exists. However, there is limited understanding
regarding breast cancer survivors' preferences for who provides their follow-up.
Our objective was to explore breast cancer survivors' perspectives on the goals
of breast cancer follow-up, the preferred role for primary care providers, and
the perceived roles of different types of oncologists during follow-up. METHODS:
A convenience sample of stage 0-III breast cancer survivors was identified and in
depth one-on-one interviews conducted. Data were analyzed using inductive content
analysis. RESULTS: Survivors cited a strong preference for oncology-based follow
up within the first 5 years after diagnosis, driven by their need for reassurance
that cancer had not recurred. Survivors also thought that their primary care
provider needed to be involved. Survivors assumed that oncology follow-up was
directed by a standard protocol that included streamlining the follow-up team.
Survivors recognized that patients with more complex cancers or challenging
treatment courses may require more intensive follow-up and deviate from the
standard protocol. Most survivors were comfortable deferring decisions regarding
who participated in follow-up to the oncology team. CONCLUSIONS: Most patients
think a streamlined approach to oncology-based breast cancer follow-up already
occurs, driven by a standard protocol. The use of a standard protocol to provide
guidance for which types of oncology providers should participate in breast
cancer follow-up will streamline care and represents a significant opportunity to
reduce unnecessary variation. This approach is especially critical given
patients' strong preferences for oncology-based follow-up.
PMID- 29332177
TI - Novel SERAC1 mutations in a Chinese patient presenting with parkinsonism and
dystonia.
PMID- 29332176
TI - Characteristics of petroleum-contaminated groundwater during natural attenuation:
a case study in northeast China.
AB - The objective of this study was to investigate a petroleum-contaminated
groundwater site in northeast China. We determined the physicochemical properties
of groundwater that contained total petroleum hydrocarbons (TPH) with a view to
developing a scientifically robust strategy for controlling and remediating
pollution of groundwater already contaminated with petroleum. Samples were
collected at regular intervals and were analyzed for dissolved oxygen (DO), iron
(Fe3+), sulfate (SO42-), electrical conductivity (Eh), pH, hydrogen carbonate
(HCO3-), and enzyme activities of catalase (CAT), peroxidase (HRP), catechol 1,2
dioxygenase (C12O), and catechol 2,3-dioxygenase (C23O). We used factor analysis
in SPSS to determine the main environmental characteristics of the groundwater
samples. The results confirmed that the study site was slightly contaminated and
that TPH levels were decreasing slightly. Some of the physicochemical variables
showed regular fluctuations; DO, Fe3+, and SO42- contents decreased gradually,
while the concentrations of one of the microbial degradation products, HCO3-,
increased. Microorganism enzyme activities decreased gradually. The
microbiological community deteriorated noticeably during the natural attenuation
process, so microbiological degradation of pollutants receded gradually. The HCO3
content increased and the pH and Eh decreased gradually. The groundwater
environment tended to be reducing.
PMID- 29332178
TI - Association of Autism with Maternal Infections, Perinatal and Other Risk Factors:
A Case-Control Study.
AB - This case-control study explores the association between pregnancy/birth
complications and other factors with Autism Spectrum Disorder (ASD) in Lebanese
subjects aged 2-18 years. Researchers interviewed 136 ASD cases from the American
University of Beirut Medical Center Special Kids Clinic, and 178 controls
selected by systematic digit dialing in the Greater-Beirut area. Male gender
(Adjusted Odds Ratio [95% CI]: 3.9 [2.2-7.0]); postpartum feeding difficulties
(2.5 [1.2-5.4]); maternal infections/complications during pregnancy (2.9 [1.5
5.5], 2.1 [1.1-3.9]); consanguinity (2.5 [1.0-6.0]); family history of
psychiatric disorders (2.2 [1.1-4.4]) were risk factors for ASD. Being born
first/second (0.52 [0.28-0.95]) and maternal psychological support during
pregnancy (0.49 [0.27-0.89]) were negatively associated with ASD. Identifying ASD
correlates is crucial for instigating timely screening and subsequent early
intervention.
PMID- 29332179
TI - Profiles and Correlates of Parent-Child Agreement on Social Anxiety Symptoms in
Youth with Autism Spectrum Disorder.
AB - This study characterized patterns and correlates of parent-youth agreement on
social anxiety in youth with and without autism spectrum disorder (ASD).
Participants (279 verbally-fluent youth aged 8-16 years, NASD = 144, NTD = 135)
completed the SASC-R. Youth with ASD exhibited higher social anxiety across
informants. While TD youth endorsed higher anxiety than did parents, self- and
parent-reports did not differ in youth with ASD. For children with ASD, higher
parent-youth agreement was associated with lower lifetime ASD symptoms and higher
adaptive skills. For TD youth, agreement on high anxiety was associated with
lowest adaptive skills. Demographic factors (age, verbal IQ, gender) did not
relate to agreement for either group. In ASD, parent-child agreement on youth
anxiety, either high or low, was associated with better outcomes.
PMID- 29332182
TI - Correction to: Pretreatment quality of life in patients with rectal cancer is
associated with intrusive thoughts and sense of coherence.
AB - The original version of this article, unfortunately, contained errors.
PMID- 29332181
TI - Management of Rotator Cuff Injuries in the Elite Athlete.
AB - PURPOSE OF REVIEW: Rotator cuff injuries are a common cause of pain and
dysfunction for the elite athlete and can result in time loss from participation.
This review highlights the current management of these injuries. RECENT FINDINGS:
Conservative management of rotator cuff injuries continues to be the "gold
standard" in the elite athlete. This includes a comprehensive rehabilitation
program, anti-inflammatories, and corticosteroid injections. Newer treatment
techniques such as intramuscular dry needling and the use of biologics such as
platelet-rich plasma and stem cells demonstrate early promising results; however,
these modalities require further investigation to determine their effectiveness.
Rotator cuff injuries can range from contusions and tendinopathy to full
thickness tears. A comprehensive evaluation is needed to determine the extent of
injury and appropriate plan of care. Management strategies can range from
rehabilitation to operative intervention and are guided by the size of the tear,
time of season, sport, performance limitations, and presence of concomitant
pathology.
PMID- 29332180
TI - CD39-adenosinergic axis in renal pathophysiology and therapeutics.
AB - Extracellular ATP interacts with purinergic type 2 (P2) receptors and elicits
many crucial biological functions. Extracellular ATP is sequentially hydrolyzed
to ADP and AMP by the actions of defined nucleotidases, such as CD39, and AMP is
converted to adenosine, largely by CD73, an ecto-5'-nucleotidase. Extracellular
adenosine interacts with P1 receptors and often opposes the effects of P2
receptor activation. The balance between extracellular ATP and adenosine in the
blood and extracellular fluid is regulated chiefly by the activities of CD39 and
CD73, which constitute the CD39-adenosinergic axis. In recent years, several
studies have shown this axis to play critical roles in transport of water/sodium,
tubuloglomerular feedback, renin secretion, ischemia reperfusion injury, renal
fibrosis, hypertension, diabetic nephropathy, transplantation, inflammation, and
macrophage transformation. Important developments include global and targeted
gene knockout and/or transgenic mouse models of CD39 or CD73, biological or small
molecule inhibitors, and soluble engineered ectonucleotidases to directly impact
the CD39-adenosinergic axis. This review presents a comprehensive picture of the
multiple roles of CD39-adenosinergic axis in renal physiology, pathophysiology,
and therapeutics. Scientific advances and greater understanding of the role of
this axis in the kidney, in both health and illness, will direct development of
innovative therapies for renal diseases.
PMID- 29332183
TI - Identification of N-arylsulfonylpyrimidones as anticancer agents.
AB - For confirming the role of five membered ring of imidazolidinone moiety of N
arylsulfonylimidazolidinones (7) previously reported with highly potent
anticancer agent, a series of N-arylsulfonylpyrimidones (10a-g) and N
arylsulfonyltetrahydropyrimidones (11a-e) were prepared and their anti
proliferating activity was measured against human cancer cell lines (renal ACHN,
colon HCT-15, breast MDA-MB-231, lung NCI-H23, stomach NUGC-3, and prostate PC-3)
using XTT assay. Among them, 1-(1-acetylindolin-5-ylsulfonyl)-4
phenyltetrahydropyrimidin-2(1H)-one (11d, mean GI50 = 3.50 uM) and ethyl 5-(2-oxo
4-phenyltetrahydropyrimidin-1(2H)-ylsulfonyl)-indoline-1-carboxylate (11e, mean
GI50 = 0.26 uM) showed best growth inhibitory activity against human cancer cell
lines. Considering the activity results, N-arylsulfonyltetrahydropyrimidones (11)
exhibited more potent activity compared to N-arylsulfonylpyrimidones (10) and
comparable activity to N-arylsulfonylimidazolidinones (7). Especially,
tetrahydropyrimidin-2(1H)-one analogs containing acylindolin-5-ylsulfonyl moiety
at position 1 demonstrated their strong growth inhibitory activity against human
cancer cell lines.
PMID- 29332184
TI - Neurologic complications of immune checkpoint inhibitors.
AB - Immune checkpoint inhibitors (ICPIs) have recently emerged as a novel treatment
for cancer. These agents, transforming the field of oncology, are not devoid of
toxicity and cause immune-related side effects which can involve any organ
including the nervous system. In this study, we present 9 patients (7 men and 2
women) with neurologic complications secondary to ICPI treatment. These included
meningoencephalitis, limbic encephalitis, polyradiculitis, cranial
polyneuropathy, myasthenic syndrome and myositis. Four patients received dual
ICPI therapy comprised of programmed cell death-1 and cytotoxic lymphocyte
associated protein-4 blocking antibodies. Median time to onset of neurologic
adverse event during immune checkpoint inhibitor treatment was 8 weeks (range 5
days-19 weeks). In all patients ICPIs were stopped and corticosteroids were
initiated, resulting in a marked improvement in seven out of nine patients. Two
patients, one with myositis and one with myasthenic syndrome, died. In two
patients ICPI therapy was resumed after resolution of the neurological adverse
event with no additional neurologic complications. This series highlights the
very broad spectrum of neurological complications of ICPIs, emphasizes the need
for expedited diagnosis and suggests that withholding treatment early,
accompanied with steroid therapy, carries the potential of complete resolution of
the neurological immune-mediated condition. Thus, a high level of suspicion and
rapid initiation of corticosteroids are mandatory to prevent uncontrolled
clinical deterioration, which might be fatal.
PMID- 29332185
TI - Handedness and the risk of glioma.
AB - Gliomas are the most common type of malignant primary brain tumor and few risk
factors have been linked to their development. Handedness has been associated
with several pathologic neurological conditions such as schizophrenia, autism,
and epilepsy, but few studies have evaluated a connection between handedness and
risk of glioma. In this study, we examined the relationship between handedness
and glioma risk in a large case-control study (1849 glioma cases and 1354 healthy
controls) and a prospective cohort study (326,475 subjects with 375 incident
gliomas). In the case-control study, we found a significant inverse association
between left handedness and glioma risk, with left-handed persons exhibiting a
35% reduction in the risk of developing glioma [odds ratio (OR) = 0.65, 95%
confidence interval (CI) 0.51-0.83] after adjustment for age, gender, race,
education, and state of residence; similar inverse associations were observed for
GBM (OR = 0.69, 95% CI 0.52-0.91), and non-GBM (OR = 0.59, 95% CI 0.42-0.82)
subgroups. The association was consistent in both males and females, and across
age strata, and was observed in both glioblastoma and in lower grade tumors. In
the prospective cohort study, we found no association between handedness and
glioma risk (hazards ratio = 0.92, 95% CI 0.67-1.28) adjusting for age, gender,
and race. Further studies on this association may help to elucidate mechanisms of
pathogenesis in glioma.
PMID- 29332186
TI - Assessment of oral cancer pain, anxiety, and quality of life of oral squamous
cell carcinoma patients with invasive treatment procedure.
AB - PURPOSE: Depending on its stage on diagnosis, oral squamous cell carcinoma (OSCC)
might cause excruciating pain and decreased quality of life. As for treatment,
the treatment of OSCC might vary from chemotherapy to surgery. The objective of
the current study was to assess the preoperative and postoperative oral cancer
pain, anxiety, and quality of life of OSCC patients with invasive treatment
procedure. METHODS: The current study was conducted by interviewing 21 (10 males;
11 females) patients who had been diagnosed with stage 3 and stage 4 OSCC and
about to go through surgery at the inpatient ward of Surgical Oncology
Department, Hasan Sadikin Hospital, Bandung, Indonesia. A preoperative and
interview was conducted by using the Hospital Anxiety and Depression Scale
(HADS), the European Organization for Research and Treatment of Cancer Quality of
Life Questionnaire (EORTC QOL)-C30, the shortened EORTC QOL Questionnaire for
Oesophageal Cancer (OES)18, the visual analog scale (VAS), and the University of
California San Francisco (UCSF) Oral Cancer Pain Questionnaire. All data were
analyzed to evaluate the preoperative and postoperative effect. RESULTS: The
current study showed a significant decrease of the postoperative oral pain (p <
0.01) and anxiety level (p < 0.01), while postoperative patient' quality of life
was significantly (p < 0.01) increased. CONCLUSION: Despite of the invasive
procedure that might cause postoperative effect, OSCC patients in the current
study showed a better quality of life after cancer removal.
PMID- 29332188
TI - Acknowledgements to Referees.
PMID- 29332187
TI - Human bite injuries to the head and neck: current trends and management protocols
in England and Wales.
AB - INTRODUCTION: Human bite injuries can be challenging in their presentation to the
examining physician. In a study by Merchant et al., 18% of patients presenting
with a human bite injury had suffered wounds to the head and neck region. Current
trends in their initial management at presentation to emergency departments
throughout England and Wales will be discussed in this paper. MATERIALS AND
METHOD: A postal survey was sent out to 100 A&E lead clinicians. This was
followed up by telephone enquiries to improve the response rate. The collated
results of the survey were entered onto a spreadsheet (Microsoft Excel(c)) for
the purpose of statistical review. RESULTS: A 68% response rate from A&E
departments throughout England and Wales demonstrated a lack of consensus in the
initial management and subsequent treatment of human bite injuries. Written
protocols are in place for human bite injuries in 54.4% of units. In 100% of
units, initial management involves irrigation +/- debridement of the wound,
though there is a lack of agreement on the surgical management of the wound.
77.9% of units follow 'needle stick protocols' when stratifying risk for blood
borne viruses. CONCLUSION: Human bites pose a number of unique problems, ranging
from cellulitis to the transmission of communicable diseases. The maxillofacial
surgeon has the added dilemmas surrounding subsequent repair and reconstruction.
Appreciation of the complexity of human bite injuries will ensure optimal care
for the patient. We propose a set of guidelines developed 'in-house' to assist in
the management of human bite injuries.
PMID- 29332189
TI - The Arabidopsis histone chaperone FACT is required for stress-induced expression
of anthocyanin biosynthetic genes.
AB - KEY MESSAGE: The histone chaperone FACT is involved in the expression of genes
encoding anthocyanin biosynthetic enzymes also upon induction by moderate high
light and therefore contributes to the stress-induced plant pigmentation. The
histone chaperone FACT consists of the SSRP1 and SPT16 proteins and associates
with transcribing RNAPII (RNAPII) along the transcribed region of genes. FACT can
promote transcriptional elongation by destabilising nucleosomes in the path of
RNA polymerase II, thereby facilitating efficient transcription of chromatin
templates. Transcript profiling of Arabidopsis plants depleted in SSRP1 or SPT16
demonstrates that only a small subset of genes is differentially expressed
relative to wild type. The majority of these genes is either up- or down
regulated in both the ssrp1 and spt16 plants. Among the down-regulated genes,
those encoding enzymes of the biosynthetic pathway of the plant secondary
metabolites termed anthocyanins (but not regulators of the pathway) are
overrepresented. Upon exposure to moderate high-light stress several of these
genes are up-regulated to a lesser extent in ssrp1/spt16 compared to wild type
plants, and accordingly the mutant plants accumulate lower amounts of anthocyanin
pigments. Moreover, the expression of SSRP1 and SPT16 is induced under these
conditions. Therefore, our findings indicate that FACT is a novel factor required
for the accumulation of anthocyanins in response to light-induction.
PMID- 29332190
TI - Transcriptomic profiling of developing fiber in levant cotton (Gossypium
herbaceum L.).
AB - Cotton (Gossypium spp.) is an imperative economic crop of the globe due to its
natural textile fiber. Molecular mechanisms of fiber development have been
greatly revealed in allotetraploid cotton but remained unexplored in Gossypium
herbaceum. G. herbaceum can withstand the rigors of nature like drought and pests
but produce coarse lint. This undesirable characteristic strongly needs the
knowledge of fiber development at molecular basis. The present study reported the
transcriptome sequence of the developing fiber of G. herbaceum on pyrosequencing
and its analysis. About 1.38 million raw and 1.12 million quality trimmed reads
were obtained followed by de novo assembly-generated 20,125 unigenes containing
14,882 coding sequences (CDs). BLASTx-based test of homology indicated that A1
derived transcripts shared a high similarity with Gossypium arboreum (A2).
Functional annotation of the CDs using the UniProt categorized them into
biological processes, cellular components, and molecular function, COG
classification showed that a large number of CDs have significant homology in COG
database (6215 CDs), and mapping of CDs with Kyoto Encyclopedia of Genes and
Genomes (KEGG) database generated 200 pathways ultimately showing predominant
engagement in the fiber development process. Transcription factors were predicted
by comparison with Plant Transcription Factor Database, and their differential
expression between stages exposed their important regulatory role in fiber
development. Differential expression analysis based on reads per kilobase of
transcript per million mapped reads (RPKM) value revealed activities of specific
gene related to carbohydrate and lipid synthesis, carbon metabolism, energy
metabolism, signal transduction, etc., at four stages of fiber development, and
was validated by qPCR. Overall, this study will help as a valuable foundation for
diploid cotton fiber improvement.
PMID- 29332192
TI - How Participatory Should Environmental Governance Be? Testing the Applicability
of the Vroom-Yetton-Jago Model in Public Environmental Decision-Making.
AB - Public participation is potentially useful to improve public environmental
decision-making and management processes. In corporate management, the Vroom
Yetton-Jago normative decision-making model has served as a tool to help managers
choose appropriate degrees of subordinate participation for effective decision
making given varying decision-making contexts. But does the model recommend
participatory mechanisms that would actually benefit environmental management?
This study empirically tests the improved Vroom-Jago version of the model in the
public environmental decision-making context. To this end, the key variables of
the Vroom-Jago model are operationalized and adapted to a public environmental
governance context. The model is tested using data from a meta-analysis of 241
published cases of public environmental decision-making, yielding three main sets
of findings: (1) The Vroom-Jago model proves limited in its applicability to
public environmental governance due to limited variance in its recommendations.
We show that adjustments to key model equations make it more likely to produce
meaningful recommendations. (2) We find that in most of the studied cases, public
environmental managers (implicitly) employ levels of participation close to those
that would have been recommended by the model. (3) An ANOVA revealed that such
cases, which conform to model recommendations, generally perform better on
stakeholder acceptance and environmental standards of outputs than those that
diverge from the model. Public environmental management thus benefits from
carefully selected and context-sensitive modes of participation.
PMID- 29332191
TI - Genome-wide characterization of differentially expressed genes provides insights
into regulatory network of heat stress response in radish (Raphanus sativus L.).
AB - Heat stress (HS) causes detrimental effects on plant morphology, physiology, and
biochemistry that lead to drastic reduction in plant biomass production and
economic yield worldwide. To date, little is known about HS-responsive genes
involved in thermotolerance mechanism in radish. In this study, a total of 6600
differentially expressed genes (DEGs) from the control and Heat24 cDNA libraries
of radish were isolated by high-throughput sequencing. With Gene Ontology (GO)
and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, some genes
including MAPK, DREB, ERF, AP2, GST, Hsf, and Hsp were predominantly assigned in
signal transductions, metabolic pathways, and biosynthesis and abiotic stress
responsive pathways. These pathways played significant roles in reducing stress
induced damages and enhancing heat tolerance in radish. Expression patterns of 24
candidate genes were validated by reverse-transcription quantitative PCR (RT
qPCR). Based mainly on the analysis of DEGs combining with the previous miRNAs
analysis, the schematic model of HS-responsive regulatory network was proposed.
To counter the effects of HS, a rapid response of the plasma membrane leads to
the opening of specific calcium channels and cytoskeletal reorganization, after
which HS-responsive genes are activated to repair damaged proteins and ultimately
facilitate further enhancement of thermotolerance in radish. These results could
provide fundamental insight into the regulatory network underlying heat tolerance
in radish and facilitate further genetic manipulation of thermotolerance in root
vegetable crops.
PMID- 29332193
TI - Melanogenesis inhibitory activity of components from Salam leaf (Syzygium
polyanthum) extract.
AB - In order to identify a novel whitening agent, the methanol extract of S.
polyanthum leaf was focused on by the screening test using nine Indonesian
medicinal plants for the inhibition of melanogenesis and tyrosinase activity in
B16 melanoma cells. Three novel compounds [(1) 1-(2,3,5-trihydroxy-4
methylphenyl)hexane-1-one, (2) 1-(2,3,5-trihydroxy methylphenyl)octane-1-one, and
(3) (4E)-1-(2,3,5-trihydroxy-4-methylphenyl)decan-1-one and one known compound
[(4) 1-(2,3,5-trihydroxy-4-methylphenyl)decan-1-one were isolated from the
methanol extract. Our study demonstrated that S. polyanthum leaf methanol extract
at 25-200 MUg/mL decreased extracellular melanin formation ca. 20-80%, with high
cell viability. Compounds 1-4 were found to be active in melanogenesis and
tyrosinase inhibition. Compound 3 was the most active against tyrosinase activity
(83.98 MUM), particularly when L-tyrosine was the substrate. Compounds 1-4
significantly diminished extracellular melanin formation in B16 melanoma cells (>
80%), with high cell viability. Thus, our study suggested that compounds 1-4
isolated from the methanol extract of S. polyanthum leaf play important roles in
decreasing extracellular melanogenesis and inhibiting tyrosinase.
PMID- 29332194
TI - The active glycosides from Urtica fissa rhizome decoction.
AB - Using bioassay guided fractionation, 16 glycosides, including two new compounds
(1 and 2), were isolated from the anticomplement and anti-inflammatory portion of
an Urtica fissa rhizome decoction used for arthritis. Several compounds were
found to possess significant anticomplement and anti-inflammatory activities.
This study revealed that glycosides played an important role in the therapeutic
effects of Urtica fissa rhizome.
PMID- 29332195
TI - Histomorphometry and cortical robusticity of the adult human femur.
AB - Recent quantitative analyses of human bone microanatomy, as well as theoretical
models that propose bone microstructure and gross anatomical associations, have
started to reveal insights into biological links that may facilitate remodeling
processes. However, relationships between bone size and the underlying cortical
bone histology remain largely unexplored. The goal of this study is to determine
the extent to which static indicators of bone remodeling and vascularity,
measured using histomorphometric techniques, relate to femoral midshaft cortical
width and robusticity. Using previously published and new quantitative data from
450 adult human male (n = 233) and female (n = 217) femora, we determine if these
aspects of femoral size relate to bone microanatomy. Scaling relationships are
explored and interpreted within the context of tissue form and function. Analyses
revealed that the area and diameter of Haversian canals and secondary osteons,
and densities of secondary osteons and osteocyte lacunae from the sub-periosteal
region of the posterior midshaft femur cortex were significantly, but not
consistently, associated with femoral size. Cortical width and bone robusticity
were correlated with osteocyte lacunae density and scaled with positive
allometry. Diameter and area of osteons and Haversian canals decreased as the
width of cortex and bone robusticity increased, revealing a negative allometric
relationship. These results indicate that microscopic products of cortical bone
remodeling and vascularity are linked to femur size. Allometric relationships
between more robust human femora with thicker cortical bone and histological
products of bone remodeling correspond with principles of bone functional
adaptation. Future studies may benefit from exploring scaling relationships
between bone histomorphometric data and measurements of bone macrostructure.
PMID- 29332197
TI - Identification as a Mutation Carrier and Effects on Life According to Experiences
of Finnish Male BRCA1/2 Mutation Carriers.
AB - Earlier studies have explored post-identification experiences of male BRCA1/2
mutation carriers, but more detailed knowledge of both their experiences and
effects of identification as a carrier on their lives is required to improve
genetic counseling. Thus, the aim of this study was to acquire deeper and broader
insights into their experiences. Qualitative data were collected from theme-based
interviews with 31 men carrying BRCA1/2 mutations in Finland, and analyzed using
inductive content analysis. Three categories of the participants' responses to
identification as BRCA1/2 mutation carriers were identified (personal, offspring
related and related to other relatives), mainly concerning issues associated with
cancer, hereditary transmission of their mutations, and life decisions. Although
there were many neutral responses regarding the issues, there were also strong
emotional reactions and cancer worries. Identification as a carrier also had
several effects on participants' lifestyles, including adoption of healthier and
disease-preventing behavior, and social well-being, such as family planning and
attitudes to life. The results provide detailed information about several aspects
of male BRCA1/2 mutation carriers' experiences, which could be used to develop a
tentative model of tailored genetic counseling for them.
PMID- 29332196
TI - Bioelectronic modulation of carotid sinus nerve activity in the rat: a potential
therapeutic approach for type 2 diabetes.
AB - AIMS/HYPOTHESIS: A new class of treatments termed bioelectronic medicines are now
emerging that aim to target individual nerve fibres or specific brain circuits in
pathological conditions to repair lost function and reinstate a healthy balance.
Carotid sinus nerve (CSN) denervation has been shown to improve glucose
homeostasis in insulin-resistant and glucose-intolerant rats; however, these
positive effects from surgery appear to diminish over time and are heavily
caveated by the severe adverse effects associated with permanent loss of
chemosensory function. Herein we characterise the ability of a novel
bioelectronic application, classified as kilohertz frequency alternating current
(KHFAC) modulation, to suppress neural signals within the CSN of rodents.
METHODS: Rats were fed either a chow or high-fat/high-sucrose (HFHSu) diet (60%
lipid-rich diet plus 35% sucrose drinking water) over 14 weeks. Neural interfaces
were bilaterally implanted in the CSNs and attached to an external pulse
generator. The rats were then randomised to KHFAC or sham modulation groups.
KHFAC modulation variables were defined acutely by respiratory and cardiac
responses to hypoxia (10% O2 + 90% N2). Insulin sensitivity was evaluated
periodically through an ITT and glucose tolerance by an OGTT. RESULTS: KHFAC
modulation of the CSN, applied over 9 weeks, restored insulin sensitivity
(constant of the insulin tolerance test [KITT] HFHSu sham, 2.56 +/- 0.41%
glucose/min; KITT HFHSu KHFAC, 5.01 +/- 0.52% glucose/min) and glucose tolerance
(AUC HFHSu sham, 1278 +/- 20.36 mmol/l * min; AUC HFHSu KHFAC, 1054.15 +/- 62.64
mmol/l * min) in rat models of type 2 diabetes. Upon cessation of KHFAC, insulin
resistance and glucose intolerance returned to normal values within 5 weeks.
CONCLUSIONS/INTERPRETATION: KHFAC modulation of the CSN improves metabolic
control in rat models of type 2 diabetes. These positive outcomes have
significant translational potential as a novel therapeutic modality for the
purpose of treating metabolic diseases in humans.
PMID- 29332198
TI - Drug Delivery and Transport into the Central Circulation: An Example of Zero
Order In vivo Absorption of Rotigotine from a Transdermal Patch Formulation.
AB - BACKGROUND AND OBJECTIVE: Pharmacokinetic studies using deconvolution methods and
non-compartmental analysis to model clinical absorption of drugs are not well
represented in the literature. The purpose of this research was (1) to define the
system of equations for description of rotigotine (a dopamine receptor agonist
delivered via a transdermal patch) absorption based on a pharmacokinetic model
and (2) to describe the kinetics of rotigotine disposition after single and
multiple dosing. METHODS: The kinetics of drug disposition was evaluated based on
rotigotine plasma concentration data from three phase 1 trials. In two trials,
rotigotine was administered via a single patch over 24 h in healthy subjects. In
a third trial, rotigotine was administered once daily over 1 month in subjects
with early-stage Parkinson's disease (PD). A pharmacokinetic model utilizing
deconvolution methods was developed to describe the relationship between drug
release from the patch and plasma concentrations. Plasma-concentration over time
profiles were modeled based on a one-compartment model with a time lag, a zero
order input (describing a constant absorption via skin into central circulation)
and first-order elimination. Corresponding mathematical models for single- and
multiple-dose administration were developed. RESULTS: After single-dose
administration of rotigotine patches (using 2, 4 or 8 mg/day) in healthy
subjects, a constant in vivo absorption was present after a minor time lag (2-3
h). On days 27 and 30 of the multiple-dose study in patients with PD, absorption
was constant during patch-on periods and resembled zero-order kinetics.
CONCLUSION: Deconvolution based on rotigotine pharmacokinetic profiles after
single- or multiple-dose administration of the once-daily patch demonstrated that
in vivo absorption of rotigotine showed constant input through the skin into the
central circulation (resembling zero-order kinetics). Continuous absorption
through the skin is a basis for stable drug exposure.
PMID- 29332199
TI - Analysis of the data on pregnancy and lactation provided by patient information
leaflets of anti-rheumatic drugs in Argentina.
AB - To analyse the level of consistency and updating of the information on pregnancy
and lactation provided by patient information leaflets (PILs) of the
antirheumatic drugs approved in Argentina. Inconsistencies between the 2016 EULAR
Task Force recommendations on the use of anti-rheumatic drugs during pregnancy
and lactation and the information provided by PILs of the same drugs approved in
Argentina were analysed along with inconsistencies within the PILs of different
registered trademarks of these drugs. Eighty-eight PILs of 32 drugs were
analysed. Out of the 88 PILs, 50% presented information inconsistencies as to
pregnancy. Medications comprised in this group were: hydroxychloroquine,
sulfasalazine, azathioprine, tacrolimus, cyclosporine, NSAIDs (during the first
two trimesters), celecoxib, some glucocorticoids, colchicine, and some anti-TNF
drugs (etanercept, adalimumab and infliximab) during part of the pregnancy. As
for lactation, 56% had information inconsistencies. Medications encompassed in
this group were: hydroxychloroquine, chloroquine, sulfasalazine, azathioprine,
tacrolimus, cyclosporine, NSAIDs, celecoxib, meprednisone, prednisone,
colchicine, and anti-TNF drugs. Out of 17 drugs that had more than one registered
trademark, information inconsistencies on pregnancy were found in the PILs of
sulfasalazine, diclofenac, ibuprofen and methylprednisolone. Concerning
lactation, inconsistencies were present in the PILs of hydroxychloroquine,
sulfasalazine, diclofenac, ibuprofen, meprednisone, and colchicine. At least half
of the PILs of anti-rheumatic drugs analysed in this study had information
inconsistencies on pregnancy and lactation. This is a serious state of affairs
because the consensual decision-making process between patient and professional
may be compromised, which, in turn, may give rise to medical-legal issues.
PMID- 29332200
TI - Simultaneous multi-slice accelerated turbo spin echo of the knee in pediatric
patients.
AB - PURPOSE: To compare knee MRI performed with the integrated parallel acquisition
technique (PAT) and simultaneous multislice (SMS) turbo spin echo (TSE) T2
weighted (T2w) sequences with conventional TSE sequences in pediatric patients.
MATERIALS AND METHODS: This was a retrospective IRB-approved study. Seventy-four
subjects (26 male, 48 female, mean age 15.3 years, range 8-20) underwent 3-T MRI
of the knee with a T2w TSE pulse sequence prototype with four-fold PAT and SMS
acceleration as well as the standard PAT-only accelerated sequences. Images were
anonymized and two study folders were created: one examination with only T2w PAT2
images (conventional examination) and one examination with only T2w SMS2/PAT2
sequences (SMS examination). Two readers rated examinations for 15 specific
imaging findings and 5 quality metrics. Interreader agreement was measured.
Signal to noise (SNR) and contrast to noise (CNR) were measured for SMS and
conventional T2w sequences. RESULTS: Consensus review demonstrated diagnostic
quality performance of SMS examinations with respect to all 15 structures.
Average area under the curve (AROC) was 0.95 and 0.97 for readers 1 and 2,
respectively. The conventional sequence was favored over SMS for four out of five
quality metrics (p < 0.001). SNR and CNR were higher for the conventional
sequences compared to SMS. CONCLUSION: SMS accelerated T2w TSE sequences offer a
faster alternative for knee imaging in pediatric patients without compromise in
diagnostic performance despite diminished SNR. The four-fold acceleration of SMS
is beneficial to pediatric patients who often have difficulty staying still for
long MRI examinations.
PMID- 29332201
TI - Gouty involvement of the patella and extensor mechanism of the knee mimicking
aggressive neoplasm. A case series.
AB - Gout is a common inflammatory crystal deposition disease that occurs in many
joints throughout the body. Active gout is most often associated with painful
synovitis causing searing joint pains, but gout can also produce large masses of
space-occupying deposits called tophi. Tophi are most frequently seen in juxta
articular locations with or without bony erosion and are often misdiagnosed as
degenerative joint disease. Soft tissue deposits and tendon involvement are also
known manifestations of gout, but can present with indeterminate and alarming
findings on imaging. We present three cases of tophaceous gout mimicking
aggressive neoplasms in the extensor mechanism of the knee. All cases presented
as extensor tendon masses eroding into the patella, with imaging findings
initially concerning for primary musculoskeletal malignancy.
PMID- 29332202
TI - Non-amidated and amidated members of the C-type allatostatin (AST-C) family are
differentially distributed in the stomatogastric nervous system of the American
lobster, Homarus americanus.
AB - The crustacean stomatogastric nervous system (STNS) is a well-known model for
investigating neuropeptidergic control of rhythmic behavior. Among the peptides
known to modulate the STNS are the C-type allatostatins (AST-Cs). In the lobster,
Homarus americanus, three AST-Cs are known. Two of these, pQIRYHQCYFNPISCF (AST-C
I) and GNGDGRLYWRCYFNAVSCF (AST-C III), have non-amidated C-termini, while the
third, SYWKQCAFNAVSCFamide (AST-C II), is C-terminally amidated. Here, antibodies
were generated against one of the non-amidated peptides (AST-C I) and against the
amidated isoform (AST-C II). Specificity tests show that the AST-C I antibody
cross-reacts with both AST-C I and AST-C III, but not AST-C II; the AST-C II
antibody does not cross-react with either non-amidated peptide. Wholemount
immunohistochemistry shows that both subclasses (non-amidated and amidated) of
AST-C are distributed throughout the lobster STNS. Specifically, the antibody
that cross-reacts with the two non-amidated peptides labels neuropil in the CoGs
and the stomatogastric ganglion (STG), axons in the superior esophageal (son) and
stomatogastric (stn) nerves, and ~ 14 somata in each commissural ganglion (CoG).
The AST-C II-specific antibody labels neuropil in the CoGs, STG and at the
junction of the sons and stn, axons in the sons and stn, ~ 42 somata in each CoG,
and two somata in the STG. Double immunolabeling shows that, except for one soma
in each CoG, the non-amidated and amidated peptides are present in distinct sets
of neuronal profiles. The differential distributions of the two AST-C subclasses
suggest that the two peptide groups are likely to serve different modulatory
roles in the lobster STNS.
PMID- 29332203
TI - Custom-made, antibiotic-loaded, acrylic cement spacers using a dental silicone
template for treatment of infected hip prostheses.
AB - PURPOSE: Antibiotic-loaded acrylic cement (ALAC) spacers are useful for treatment
of infected prostheses in the course of a two-stage revision. Spacers are
handmade or are made using a commercial template, with reportedly good treatment
outcomes. This study aimed to confirm the usefulness of custom-made ALAC spacers
shaped like bipolar hip prostheses using a dental silicone template for treatment
of infected hip prostheses, and described their manufacture. METHODS: This study
evaluated 10 patients who underwent two-stage revision for treatment of infected
hip prostheses. Custom-made ALAC spacers were used in all patients. Templates
were made with dental silicone. We investigated the following in treatment of the
infected hip prostheses: bacterial pathogens; antibiotic-cement mixtures; waiting
time to revision; dislocation, breakage, and migration of custom-made ALAC
spacers; current hip status; progress during follow-up; presence or absence of
recurrence; and walking ability. RESULTS: Dislocation, breakage, and migration
were not observed in custom-made ALAC spacers. All patients recovered after two
stage revision without additional surgery and showed no recurrence during the
follow-up period. CONCLUSION: Custom-made ALAC spacers shaped like bipolar hip
prostheses using a template made of dental silicone may be useful for treatment
of infected hip prostheses.
PMID- 29332204
TI - Supplementing living kidney transplantees' medical records with donor- and
recipient-narratives.
AB - Norway provides total social welfare coverage for organ transplantations,
including free immunosuppressive medication and prepaid life-long follow up for
both recipients and donors. Despite these benefits the proportion of living
kidney donors (LKD) has in recent years declined from around 40% (2011) of all
kidney transplantations to 24% (2016). This study suggests harnessing patient-
and donor-narratives as a tool for addressing the current fall in donation rates.
The hospital records of 18 recipient/donor dyads were compared with patient and
donor accounts elicited in semi-structured interviews. Narratives afford a
pertinent supplement to the primarily biomedical and technical information stored
in medical records. Even in condensed form, the messages embedded in narratives
contribute to a 'thicker' understanding of the complexity of living kidney
donation (LKD)-decisions. Narratives represent a source of education for
referring-nephrologists wishing to deepen their evaluation skills and avoid
making decisions based on insufficient insight into patients' and potential
donors' values and life-situation. Recipients' and donors' unedited accounts of
their motivations, worries, doubts and expectations afford a revealing and
edifying supplement to the primarily biomedical and technical information stored
in medical records. In narratives, the predicaments and dilemmas surrounding LKD
become visible and debatable and can serve as support for future donors,
recipients and the nephrologists responsible for evaluation-conclusions.
Generating narratives raises a number of practical, epistemic and normative
challenges.
PMID- 29332205
TI - Microbiome in psychiatry: where will we go?
PMID- 29332206
TI - Oncological outcomes after cytoreductive nephrectomy for patients with metastatic
renal cell carcinoma with inferior vena caval tumor thrombus.
AB - BACKGROUND: To evaluate the oncological outcomes of patients with metastatic
renal cell carcinoma (mRCC) involving the inferior vena cava (IVC) who received
cytoreductive nephrectomy. METHODS: This study included 75 consecutive metastatis
renal cell carcinoma (mRCC) patients with inferior vena cava (IVC) tumor thrombus
undergoing cytoreductive nephrectomy and tumor thrombectomy followed by systemic
therapy. RESULTS: Of the 75 patients, 11, 33, 24 and 7 had level I, II, III and
IV IVC thrombus, respectively. Following surgical treatment, 25 (group A), 27
(group B) and 23 (group C) received cytokine therapy alone, molecular-targeted
therapy alone and both therapies, respectively, as management for metastatic
diseases. The median overall survival (OS) of the 75 patients was 16.2 months. No
significant differences in OS were noted according to the level of the IVC tumor
thrombus. There were no significant differences in OS among groups A, B and C;
however, OS in groups B and C was significantly superior to that in group A.
Furthermore, multivariate analysis of several parameters identified the following
independent predictors of poor OS-elevated C-reactive protein, liver metastasis
and postoperative treatment with cytokine therapy alone. CONCLUSIONS: The
prognosis of mRCC patients with IVC thrombus undergoing cytoreductive nephrectomy
may be significantly affected by the type of postoperative systemic therapy
rather than the level of the IVC tumor thrombus. Accordingly, cytoreductive
nephrectomy should be considered as a major therapeutic option for patients with
mRCC involving the IVC, particularly in the era of targeted therapy.
PMID- 29332207
TI - Skeletal muscle expression of p43, a truncated thyroid hormone receptor alpha,
affects lipid composition and metabolism.
AB - Thyroid hormone is a major regulator of metabolism and mitochondrial function.
Thyroid hormone also affects reactions in almost all pathways of lipids
metabolism and as such is considered as the main hormonal regulator of lipid
biogenesis. The aim of this study was to explore the possible involvement of p43,
a 43 Kda truncated form of the nuclear thyroid hormone receptor TRalpha1 which
stimulates mitochondrial activity. Therefore, using mouse models overexpressing
p43 in skeletal muscle (p43-Tg) or lacking p43 (p43-/-), we have investigated the
lipid composition in quadriceps muscle and in mitochondria. Here, we reported in
the quadriceps muscle of p43-/- mice, a fall in triglycerides, an inhibition of
monounsaturated fatty acids (MUFA) synthesis, an increase in elongase index and
an decrease in desaturase index. However, in mitochondria from p43-/- mice, fatty
acid profile was barely modified. In the quadriceps muscle of p43-Tg mice, MUFA
content was decreased whereas the unsaturation index was increased. In addition,
in quadriceps mitochondria of p43-Tg mice, we found an increase of linoleic acid
level and unsaturation index. Last, we showed that cardiolipin content, a key
phospholipid for mitochondrial function, remained unchanged both in quadriceps
muscle and in its mitochondria whatever the mice genotype. In conclusion, this
study shows that muscle lipid content and fatty acid profile are strongly
affected in skeletal muscle by p43 levels. We also demonstrate that regulation of
cardiolipin biosynthesis by the thyroid hormone does not imply p43.
PMID- 29332208
TI - Localised aggressive periodontitis in a 3-year-old-boy.
AB - BACKGROUND: Localised aggressive periodontitis (LAgP), characterised by rapid
attachment and bone loss, which may occur in children and adolescents, without
clinical evidence of systemic disease. CASE REPORT: Three-year-old boy was
referred with excessive mobility of 83 and exfoliation of 73. Clinical
examination revealed acceptable oral hygiene. Blood tests were performed to
evaluate PMNs activity and the parents were advised to apply 0.2% chlorhexidine
twice a day. One month later 83 was still excessively mobile. Blood tests were
normal. TREATMENT: A full mouth scaling and curettage were performed under
general anaesthesia. Since 83 had been spontaneously exfoliated one day earlier,
a biopsy was taken from its socket. The biopsy examination revealed granulation
tissue with actinomyces colonies. A course of amoxicillin 250 mg three times a
day for 7 days was prescribed. Cultures from periodontal pockets of the child's
family members were found negative to Aggregatibacter actinomycetem comitans
(Aa). FOLLOW-UP: Examination 3 months later, no tooth mobility was observed and
the cultures from the periodontal pockets were negative to Aa. Thereafter, the
child was periodically reviewed every 3 months for 26 months with no signs of
periodontal disease. CONCLUSION: Amoxicillin combined with curettage around the
involved teeth may be effective in LAgP treatment.
PMID- 29332209
TI - The rapid diagnosis of viral respiratory tract infections and its impact on
antimicrobial stewardship programs.
AB - We aimed to describe the potential benefit of new rapid molecular respiratory
tests (MRT) in decreasing inappropriate antibiotic use among the inpatients
presenting with influenza-like illness (ILI). We included patients from inpatient
and outpatient departments who had ILI and performed MRT between 1 January 2015
and 31 December 2016 in a 265-bed private hospital in Istanbul. At the end of
2015, we implemented antimicrobial stewardship including systematic use of MRT.
Then, we compared our observations between the year 2015 and the year 2016. We
designed the study according to the STrengthening the Reporting of OBservational
studies in Epidemiology (STROBE) tool. A U.S. Food and Drug Administration (FDA)
cleared multiplexed polymerase chain reaction (PCR) system (BioFire FilmArray,
Idaho Technology, Salt Lake City, UT) which detects 17 viruses and three bacteria
was used for diagnosis. In total, 1317 patients were included; 630 (48%) were
inpatients and 569 (43%) were older than 16 years of age. At least one virus was
detected in 747 (57%) patients. Rhinovirus/enterovirus, influenza virus, and
adenovirus were the most commonly detected. Among hospitalized patients, in
children, a significant decrease in antibiotic use (44.5% in 2015 and 28.8% in
2016, p = 0.009) was observed, but in adults, the decrease was not statistically
significant (72% in 2015 and 63% in 2016, p = 0.36). The duration of antibiotic
use after the detection of virus was significantly decreased in both children and
adults (p < 0.001 and p = 0.007, respectively). By using MRT, inappropriate
antibiotic use and, also, duration of inappropriate antibiotic use after the
detection of virus was significantly decreased. It is time to increase the
awareness about the viral etiology in respiratory tract infections (RTIs) and
implement MRT in clinical practice.
PMID- 29332210
TI - Pathogen-specific leptospiral proteins in urine of patients with febrile illness
aids in differential diagnosis of leptospirosis from dengue.
AB - Leptospirosis and dengue are two commonly seen infectious diseases of the
tropics. Differential diagnosis of leptospirosis from dengue fever is often
difficult due to overlapping clinical symptoms and lack of economically viable
and easy-to-perform laboratory tests. The gold standard for diagnosis is the
microscopic agglutination test (MAT). In this study, the diagnostic potential of
screening for pathogen-specific leptospiral antigens in urine samples is
presented as a non-invasive method of disease diagnosis. In a study group of 40
patients, the serum was tested for anti-leptospiral antibodies by MAT and enzyme
linked immunosorbent assay (ELISA). Urine of these patients was screened for
leptospiral antigens by ELISA using specific antibodies against LipL32, LipL41,
Fla1, HbpA and sphingomyelinase. Group I patients (n = 23) were classified as
leptospirosis-positive based on MAT and high titres of circulating IgM-specific
anti-leptospiral antibodies. All of these patients excreted all five leptospiral
antigens in the urine. The 17 MAT-negative cases included six patients with
pyrexia of unknown origin (PUO; Group II) and 11 confirmed dengue patients (Group
III). The latter tested negative for both serum anti-leptospiral antibodies and
urinary leptospiral antigens. A salient outcome of this study was highlighting
the usefulness of screening for urinary leptospiral antigens in disease
diagnosis, as their presence confirmed leptospiral aetiology in two PUO patients.
Immunoblots of urinary antigens identified well-defined bands corresponding to
LipL32, HbpA and sphingomyelinase; the significance of the 42- and 58-kDa
sphingomyelinase bands is discussed.
PMID- 29332211
TI - Testosterone-mediated upregulation of delayed rectifier potassium channel in
cardiomyocytes causes abbreviation of QT intervals in rats.
AB - Men have shorter rate-corrected QT intervals (QTc) than women, especially at the
period of adolescence or later. The aim of this study was to elucidate the long
term effects of testosterone on cardiac excitability parameters including
electrocardiogram (ECG) and potassium channel current. Testosterone shortened QT
intervals in ECG in castrated male rats, not immediately after, but on day 2 or
later. Expression of Kv7.1 (KCNQ1) mRNA was significantly upregulated by
testosterone in cardiomyocytes of male and female rats. Short-term application of
testosterone was without effect on delayed rectifier potassium channel current
(IKs), whereas IKs was significantly increased in cardiomyocytes treated with
dihydrotestosterone for 24 h, which was mimicked by isoproterenol (24 h). Gene
selective inhibitors of a transcription factor SP1, mithramycin, abolished the
effects of testosterone on Kv7.1. Testosterone increases Kv7.1-IKs possibly
through a pathway related to a transcription factor SP1, suggesting a genomic
effect of testosterone as an active factor for cardiac excitability.
PMID- 29332213
TI - Survivorship care plan outcomes for primary care physicians, cancer survivors,
and systems: a scoping review.
AB - PURPOSE: With the focus on survivorship care-coordination between oncology and
primary care providers (PCPs), there is a need to assess the research regarding
the use of survivorship care plans (SCPs) and determine emerging research areas.
We sought to find out how primary care physicians have been involved in the use
of SCPs and determine SCP's effectiveness in improving care for cancer survivors.
In this scoping review, we aimed to identify gaps in the current research and
reveal opportunities for further research. METHODS: We followed the methodology
for scoping studies which consists of identifying the research question, locating
relevant studies, selecting studies, charting the data, and collating,
summarizing, and reporting the results. RESULTS: Out of 5375 original articles
identified in the literature search, 25 met the inclusion/exclusion criteria.
Eight articles examined PCP-only related outcomes, eight examined survivor-only
related outcomes, eight examined mixed outcomes between both groups, and one
examined system-based outcomes. Findings highlighted several areas where SCPs may
provide benefits, including increased confidence among PCPs in managing the care
of survivors and increased quality of life and well-being for survivors. This
research also highlighted the need for careful consideration of SCP mode of
delivery and content in order to maximize their utility to patients and
providers. CONCLUSIONS: Based on the findings of this review, SCPs may benefit
providers and health care systems, but the benefits to patients remain unclear.
Further research on the potential benefits of SCPs to particular patient
populations is warranted. IMPLICATIONS FOR CANCER SURVIVORS: SCPs appear to be
beneficial to PCPs in improving overall quality of care. However, more work needs
to be done to understand the direct impact on cancer survivors.
PMID- 29332212
TI - Measurement of [Cl-]i unaffected by the cell volume change using MQAE-based two
photon microscopy in airway ciliary cells of mice.
AB - MQAE is a 'non-ratiometric' chloride ion (Cl-)-quenched fluorescent indicator
that is used to determine intracellular Cl- concentration ([Cl-]i). MQAE-based
two-photon microscopy is reported to be a useful method to measure [Cl-]i, but it
is still controversial because a change in cell volume may alter the MQAE
concentration, leading to a change in the fluorescence intensity without any
change in [Cl-]i. In an attempt to elucidate the effect or lack of effect of cell
volume on MQAE concentration, we studied the effects of changes in cell volume,
achieved by applying different levels of osmotic stress, on the intensity of MQAE
fluorescence in airway ciliary cells. To study solely the effect of changes in
cell volume on MQAE fluorescence intensity, i.e., excluding the effect of any
change in [Cl-]i, we first conducted the experiments in a Cl--free nitrate (NO3-)
solution to substitute NO3- (non-quenching anion for MQAE fluorescence) for Cl-
in the intracellular fluid. Hypo- (- 30 mM NaNO3) or hyper-osmotic stress (+ 30
mM NaNO3) effected changes in cell volume, but the stress did not result in any
significant change in MQAE fluorescence intensity. The experiments were also
carried out in Cl--containing solution. Hypo-osmotic stress (- 30 mM NaCl)
increased both MQAE fluorescence intensity and cell volume, while hyper-osmotic
stress (+ 30 mM NaCl) decreased both of these properties. These results suggest
that the osmotic stress-induced change in MQAE fluorescence intensity was caused
by the change in [Cl-]i and not by the MQAE concentration. Moreover, the
intracellular distribution of MQAEs was heterogeneous and not affected by the
changes in osmotic stress-induced cell volume, suggesting that MQAEs are bound to
un-identified subcellular structures. These bound MQAEs appear to have enabled
the measurement of [Cl-]i in airway ciliary cells, even under conditions of cell
volume change.
PMID- 29332214
TI - Targeted Next-Generation Sequencing in Patients with Non-syndromic Congenital
Heart Disease.
AB - Congenital heart disease (CHD) is a genetically heterogeneous disease. Targeted
next-generation sequencing (NGS) offers a unique opportunity to sequence multiple
genes at lower cost and effort compared to Sanger sequencing. We tested a
targeted NGS of a specific gene panel in a relatively large population of non
syndromic CHD patients. The patient cohort comprised 68 CHD patients (45 males;
8.3 +/- 1.7 years). Amplicon libraries for 16 CHD-strictly related genes were
generated using a TruSeq(r) Custom Amplicon kit (Illumina, CA) and sequenced
using the Illumina MiSeq platform. Sequence data were processed through the MiSeq
Reporter and wANNOVAR softwares. After applying stringent filtering criteria, 20
missense variants in 9 genes were predicted to be damaging and were validated by
Sanger sequencing with 100% concordance. Fourteen variants were present in public
databases with very rare allele frequency, of which four variants (p.Arg25Cys in
NKX2-5, p.Val763Ile in ZFPM2, p.Arg1398Gln and Gly1826Asp in MYH6) have been
previously linked to CHD or cardiomyopathy. The remaining six variants in four
genes (GATA4, NKX2-5, NOTCH1, TBX1) were novel mutations, currently not found in
public databases, and absent in 200 control alleles of healthy subjects. Four
patients (5.8%) carried two missense variants (1 compound heterozygote in the
same gene and 3 double heterozygotes in different genes), with possibly
synergistic deleterious effects. Targeted NGS is a powerful and efficient tool to
detect DNA sequence variants in multiple genes, providing the opportunity for
discovery of the co-occurrence of two or more missense rare variants.
PMID- 29332215
TI - Heparin-Coated Grafts Reduce Mortality in Pediatric Patients Receiving Systemic
to-Pulmonary Shunts.
AB - We aimed to evaluate the outcomes of systemic-to-pulmonary (SP) shunt procedures
utilizing heparin-coated (HC) polytetrafluoroethylene (PTFE) vascular grafts
compared to uncoated (non-HC) grafts, in order to observe any benefits in
pediatric patients. Our institution switched from using non-HC grafts to HC
grafts in March 2011. We conducted a retrospective review of consecutive
pediatric patients receiving SP shunts from May 2008 to December 2015.
Perioperative variables including baseline characteristics, morbidity, mortality,
and blood product utilization were evaluated between the HC and non-HC groups. A
total of 142 pediatric patients received SP shunts during the study period: 69
patients received HC shunts and 73 patients received non-HC shunts. The HC group
had significantly fewer desaturation or arrest events (P < 0.01), fewer shunt
occlusions/thromboses (P < 0.01). There was no statistically significant
difference in unplanned reoperations between groups (P = 0.18). The HC group
demonstrated significantly lower overall 30-day mortality (P < 0.01), as well as
shunt-related mortality (P < 0.01). The HC group had significantly lower
postoperative packed red blood cell utilization as compared to the non-HC group
(P < 0.01). In this study, pediatric patients receiving HC PTFE grafts in SP
shunts demonstrated significantly lower shunt-related mortality. The majority of
HC grafts remained patent. These findings suggest that HC grafts used in SP shunt
procedures may benefit pediatric patients in terms of efficacy and outcomes.
PMID- 29332216
TI - Characteristics of ARG-carrying plasmidome in the cultivable microbial community
from wastewater treatment system under high oxytetracycline concentration.
AB - Studies on antibiotic production wastewater have shown that even a single
antibiotic can select for multidrug resistant bacteria in aquatic environments.
It is speculated that plasmids are an important mechanism of multidrug resistance
(MDR) under high concentrations of antibiotics. Herein, two metagenomic libraries
were constructed with plasmid DNA extracted from cultivable microbial communities
in a biological wastewater treatment reactor supplemented with 0 (CONTROL) or 25
mg/L of oxytetracycline (OTC-25). The OTC-25 plasmidome reads were assigned to 72
antibiotic resistance genes (ARGs) conferring resistance to 13 types of
antibiotics. Dominant ARGs, encoding resistance to tetracycline, aminoglycoside,
sulfonamide, and multidrug resistance genes, were enriched in the plasmidome
under 25 mg/L of oxytetracycline. Furthermore, 17 contiguous multiple-ARG
carrying contigs (carrying >= 2 ARGs) were discovered in the OTC-25 plasmidome,
whereas only nine were found in the CONTROL. Mapping of the OTC-25 plasmidome
reads to completely sequenced plasmids revealed that the conjugative IncU
resistance plasmid pFBAOT6 of Aeromonas caviae, carrying multidrug resistance
transporter (pecM), tetracycline resistance genes (tetA, tetR), and transposase
genes, might be a potential prevalent resistant plasmid in the OTC-25 plasmidome.
Additionally, two novel resistant plasmids (containing contig C301682 carrying
multidrug resistant operon mexCD-oprJ and contig C301632 carrying the tet36 and
transposases genes) might also be potential prevalent resistant plasmids in the
OTC-25 plasmidome. This study will be helpful to better understand the role of
plasmids in the development of MDR in water environments under high antibiotic
concentrations.
PMID- 29332217
TI - A novel glucuronoyl esterase from Aspergillus fumigatus-the role of conserved Lys
residue in the preference for 4-O-methyl glucuronoyl esters.
AB - Cellulose in plant cell walls is mainly covered by hemicellulose and lignin, and
thus efficient removal of these components is thought to be a key step in the
optimal utilization of lignocellulose. The recently discovered carbohydrate
esterase (CE) 15 family of glucuronoyl esterases (GEs) which cleave the linkages
between the free carboxyl group of D-glucuronic acid in hemicellulose and the
benzyl groups in lignin residues could contribute to this process. Herein, we
report the identification, functional expression, and enzymatic characterization
of a GE, AfGE, from the filamentous fungus Aspergillus fumigatus. AfGE was
heterologously expressed in Aspergillus oryzae, and the purified enzyme displayed
the ability to degrade the synthetic substrates mimicking the ester linkage
between hemicellulose and lignin. AfGE is a potentially industrially applicable
enzyme due to its characteristic as a thermophilic enzyme with the favorable
temperature of 40-50 degrees C at pH 5. Molecular modeling and site-directed
mutagenesis studies of AfGE demonstrated that Lys209 plays an important role in
the preference for the substrates containing 4-O-methyl group in the
glucopyranose ring.
PMID- 29332218
TI - Effects of sleep hygiene training given to pregnant women with restless leg
syndrome on their sleep quality.
AB - PURPOSE: This research was conducted to determine the effects of sleep hygiene
training given to pregnant women with restless leg syndrome on their sleep
quality. METHODS: This study was conducted using a quasi-experimental design with
pre-test and post-test, and a control group. When the power analysis was made, a
sample size with 5% two-sided significance, 95% confidence interval, and 95%
ability to represent the population was calculated to have a total of 128
pregnant women. The sleeping hygiene training was given to two sessions of the
experiment group. A personal identification form and the Pittsburgh Sleep Quality
Index were used for the collection of data. Percentage distribution, arithmetic
mean, standard deviation, and chi-square were used for statistical evaluation in
addition to dependent and independent groups t tests. RESULTS: PSQI pre-test mean
values revealed that sleep quality in both groups was similarly poor (p = 0.353).
It was determined that the mean post-test score after sleep hygiene training was
7.23 +/- 2.17 in the experiment group and 10.54 +/- 2.20 in the control group,
while the difference between the groups was statistically significant (p =
0.000). Accordingly, it was determined that the sleepers in the experimental
group had better sleep quality than those in the control group. CONCLUSIONS:
Sleep hygiene training given to pregnant women with restless leg syndrome
increased sleep quality.
PMID- 29332220
TI - Perinatal outcomes of unplanned out-of-hospital deliveries: a case-control study.
AB - PURPOSE: To compare the pregnancy and perinatal outcomes of unplanned home or car
births vs. in-hospital deliveries. METHODS: A retrospective, case-control study
of women who underwent unplanned out-of-hospital deliveries vs. in-hospital
deliveries from 2004 through 2014. Matching was based on gestational age and
parity in a ratio of 2:1. RESULTS: There were no significant differences between
the groups regarding demographic criteria, prenatal care and delivery
complications. Women who delivered out of hospital (n = 90) had significantly
fewer cesarean deliveries (1.1 vs. 10.6%; p = 0.05) and operative deliveries (2.2
vs. 13.3%; p = 0.004) in their obstetrical history than did the control group (n
= 180). Significantly more newborns delivered out of the hospital had
polycythemia (25.6 vs. 1.7%; p < 0.0001) and hypothermia (3.3 vs. 0%; p = 0.036)
compared to the control group. CONCLUSION: Women with unplanned out-of-hospital
deliveries tend to have fewer complications in their previous deliveries. Higher
rates of polycythemia and hypothermia require attention for neonates born out of
the hospital.
PMID- 29332221
TI - German words: still used by Japanese obstetrics and gynecology doctors.
AB - BACKGROUND: German used to be frequently employed in Japanese obstetric and
gynecologic (OBGYN) practice; however, it is now less frequently used.
Description and analysis of this situation may shed some light on the change of
OBGYN practice and education in Japan, which may at least partly hold true to
counties other than Japan. METHODS: Three eras were classified according to the
relationship between German and Japanese OBGYN, with each era characterized.
Frequently used German words in Japanese OBGYN practice were described as
examples. RESULTS: German words have become less frequently used with each
successive generation. CONCLUSIONS: Even though English may suffice in practical
OBGYN practice, German usage will still be passed on to these new generations.
PMID- 29332219
TI - Desensitisation strategies in high-risk children before kidney transplantation.
AB - BACKGROUND: Transplantation is the preferred modality for renal replacement
therapy in children. With increasing rates of re-transplantation within the
paediatric population, there are more sensitised children on waiting lists. One
issue with developing strategies to treat these children is the number of
different definitions of sensitisation. and we would therefore recommend an
immunological risk stratification approach. METHODS: We discuss methods of
sensitisation prevention, assessment and management, including paired exchange
programmes and desensitisation protocols. RESULTS: There are limited published
evidence-based data for desensitisation in adults and none in children; thus, we
present information on the available therapies currently in use. DISCUSSION:
Further research is required to investigate strategies which prevent
sensitisation in children, including the healthcare utility of incorporating
epitope-based matching into organ allocation algorithms. Controlled studies are
also needed to establish the most appropriate desensitisation regimen(s).
PMID- 29332222
TI - Efficacy of Crocus sativus (saffron) in treatment of major depressive disorder
associated with post-menopausal hot flashes: a double-blind, randomized, placebo
controlled trial.
AB - PURPOSE: Due to concerns regarding the side effects of hormone therapy, many
studies have focused on the development of non-hormonal agents for treatment of
hot flashes. The aim of this study was to evaluate the efficacy and safety of
saffron (stigma of Crocus sativus) in treatment of major depressive disorder
associated with post-menopausal hot flashes. METHODS: Sixty women with post
menopausal hot flashes participated in this study. The patients randomly received
either saffron (30 mg/day, 15 mg twice per day) or placebo for 6 weeks. The
patients were assessed using the Hot Flash-Related Daily Interference Scale
(HFRDIS), Hamilton Depression Rating Scale (HDRS) and the adverse event checklist
at baseline and also at the second, fourth, and sixth weeks of the study.
RESULTS: Fifty-six patients completed the trial. Baseline characteristics of the
participants did not differ significantly between the two groups. General linear
model repeated measures demonstrated significant effect for time * treatment
interaction on the HFRDIS score [F (3, 162) = 10.41, p = 0.0001] and HDRS score
[F (3, 162) = 5.48, p = 0.001]. Frequency of adverse events was not significantly
different between the two groups. CONCLUSIONS: Results from this study revealed
that saffron is a safe and effective treatment in improving hot flashes and
depressive symptoms in post-menopausal healthy women. On the other hand, saffron,
with fewer side effects, may provide a non-hormonal and alternative herbal
medicine option in treatment of women with hot flashes.
PMID- 29332223
TI - Long-term efficacy of partial splenic embolization for the treatment of steroid
resistant chronic immune thrombocytopenia.
AB - Thrombopoietin-receptor agonists have been recently introduced for a second-line
treatment of immune thrombocytopenia (ITP). Splenectomy has tended to be avoided
because of its complications, but the response rate of splenectomy is 60-80% and
it has still been considered for steroid-refractory ITP. We performed partial
splenic embolization (PSE) as an alternative to splenectomy. Between 1988 and
2013, 91 patients with steroid-resistant ITP underwent PSE at our hospital, and
we retrospectively analyzed the efficacy and long-term outcomes of PSE. The
complete response rate (CR, platelets > 100 * 109/L) was 51% (n = 46), and the
overall response rate (CR plus response (R), > 30 * 109/L) was 84% (n = 76). One
year after PSE, 70% of patients remained CR and R. The group with peak platelet
count after PSE >= 300 * 109/L (n = 29) exhibited a significantly higher platelet
count than the group with platelet count < 300 * 109/L (n = 40) at any time point
after PSE. The failure-free survival (FFS) rates at 1, 5, and 10 years were 78,
56, and 52%, respectively. Second PSE was performed in 20 patients who relapsed
(n = 14) or had no response to the initial PSE (n = 6), and the overall response
was achieved in 63% patients. There were no PSE-related deaths. These results
indicate that PSE is a safe and effective alternative therapy to splenectomy for
patients with steroid-resistant ITP as it generates long-term, durable responses.
PMID- 29332224
TI - Phosphatidylserine-exposing blood and endothelial cells contribute to the
hypercoagulable state in essential thrombocythemia patients.
AB - The mechanisms of thrombogenicity in essential thrombocythemia (ET) are complex
and not well defined. Our objective was to explore whether phosphatidylserine
(PS) exposure on blood cells and endothelial cells (ECs) can account for the
increased thrombosis and distinct thrombotic risks among mutational subtypes in
ET. Using flow cytometry and confocal microscopy, we found that the levels of PS
exposing erythrocytes, platelets, leukocytes, and serum-cultured ECs were
significantly higher in each ET group [JAK2, CALR, and triple-negative (TN) (all
P < 0.001)] than those in controls. Among ET patients, those with JAK2 mutations
showed higher levels of PS-positive erythrocytes, platelets, neutrophils, and
serum-cultured ECs than TN patients or those with CALR mutations, which show
similar levels. Coagulation function assays showed that higher levels of PS
positive blood cells and serum-cultured ECs led to markedly shortened coagulation
time and dramatically increased levels of FXa, thrombin, and fibrin production.
This procoagulant activity could be largely blocked by addition of lactadherin
(approx. 70% inhibition). Confocal microscopy showed that the FVa/FXa complex and
fibrin fibrils colocalized with PS on ET serum-cultured ECs. Additionally, we
found a relationship between D-dimer, prothrombin fragment F1 + 2, and PS
exposure. Our study reveals a previously unrecognized link between
hypercoagulability and exposed PS on cells, which might also be associated with
distinct thrombotic risks among mutational subtypes in ET. Thus, blocking PS
binding sites may represent a new therapeutic target for preventing thrombosis in
ET.
PMID- 29332226
TI - Monocortical fixation of the coracoid in the Latarjet procedure is significantly
weaker than bicortical fixation.
AB - PURPOSE: A crucial step of the Latarjet procedure is the fixation of the coracoid
process onto the glenoid. Multiple problems associated with the fixation have
been described, including lesions of the suprascapular nerve due to prominence of
the screw or bicortical drilling. The purpose of the present study was to
evaluate whether monocortical fixation, without perforating the posterior glenoid
cortex, would provide sufficient graft stability. METHODS: Coracoid transfer was
performed in 14 scapula models (Sawbones(r), Composite Scapula, 4th generation).
Two groups were assigned: in one group, fixation was achieved with two screws
that did not perforate the posterior cortex of the glenoid neck (monocortical
fixation), in the other group, fixation was achieved with perforation of the
posterior cortex (bicortical fixation). The ultimate failure load and mode of
failure were evaluated biomechanically. RESULTS: Monocortical fixation was a
significantly weaker construct than bicortical fixation (median failure load 221
N, interquartile range 211-297 vs. median failure load 423 N, interquartile range
273-497; p = 0.017). Failure was either due to a pullout of the screws from the
socket or a fracture of the glenoid. There was no significant difference in the
mode of failure between the two groups (n.s.). CONCLUSION: Monocortical fixation
was significantly weaker than bicortical fixation. However, bicortical drilling
and overly long screws may jeopardize the suprascapular nerve. Thus, anatomic
knowledge about the safe zone at the posterior rim of the glenoid is crucial.
Until further research has evaluated, if the inferior stability is clinically
relevant, clinicians should be cautious to use a monocortical fixation technique
for the coracoid graft.
PMID- 29332225
TI - Over 90 % of children and adolescents return to sport after anterior cruciate
ligament reconstruction: a systematic review and meta-analysis.
AB - PURPOSE: To evaluate the rate at which children and adolescent athletes return to
sporting activities after anterior cruciate ligament (ACL) reconstruction.
METHODS: Three databases, PubMed, MEDLINE, and EMBASE, were searched from
database inception until September 9, 2017 by two reviewers independently and in
duplicate. The inclusion criteria were English language studies that reported
return to sport outcomes. Book chapters, conference papers, review articles, and
technical reports were excluded. The rate of return to sports was combined in a
meta-analysis of proportions using a random-effects model. RESULTS: Overall, 20
studies with a combined total of 1156 ACL reconstructions met the inclusion
criteria, with a mean age of 14.3 years (range 6-19) and a mean follow-up time of
6.5 years (range 1-22). All studies were level IV evidence (14 retrospective case
series and 6 prospective case series). The pooled rate of return to any sport
participation was 92.0% [95% confidence interval (CI), 86-96%]. The pooled rate
of return to pre-injury level of sport was 78.6% (95% CI 71-86%) and that to
competitive level of sport was 81.0% (95% CI 62-94%). A total of 93 of the 717
assessed athletes (13%) sustained re-injuries with graft ruptures, and in 91 of
652 patients (14%), contralateral ACL injuries were reported on final follow-up.
CONCLUSION: Pooled results suggest a high rate of return to sport following ACL
reconstruction in children and adolescent athletes; however, this is associated
with a relatively high rate of graft rupture and a similar rate of contralateral
ACL injury. This study provides clinicians with evidence-based data on the
ability of children and adolescent athletes to return to sport after ACL
reconstruction, an important consideration for athletes of this population with
ACL injuries. LEVEL OF EVIDENCE: IV, systematic review of level IV studies.
PMID- 29332227
TI - Accommodative esotropia: the state of the art.
AB - PURPOSE: To review the state of the art of Accommodative Esotropia (AE) through
careful study of what has been reported up to the point in literature. METHODS: A
literature search was done on PubMed using key words including "Accommodative
esotropia", "Infantile esotropia", "Strabismus" and "Accommodation". We
systematically reviewed and critically appraised what has been written about AE
and we tried to analyze that according to the current management of AE. RESULTS:
Accommodative Esotropia (AE) is a form of strabismus characterized by convergent
misalignment of the visual axes that can be associated with hyperopia and
abnormal fusional divergence. Also abnormal accommodative
convergence/accommodation ratio could be found. In lots of cases, AE initially
presents as an intermittent esodeviation at age 1.5 to 4 years. The prevalence of
AE has been estimated near 1-2% in the United States. The only treatment with an
optical correction usually is successful in re-establishing alignment, but
surgical correction is necessary in approximately 30% of cases.
PMID- 29332228
TI - Comparative evaluation of the aqueous humor proteome of primary angle closure and
primary open angle glaucomas and age-related cataract eyes.
AB - PURPOSE: To analyze and compare the total proteome of aqueous humor (AH) from
patients having primary angle closure glaucoma (PACG), primary open angle
glaucoma (POAG) and age-related cataract. MATERIALS AND METHODOLOGY: Aqueous
humor was collected from age-matched PACG, POAG and cataract patients who
underwent surgery, and it was immediately stored at - 80 degrees C until
analysis. From each sample, 25 ug of total protein was subjected to trypsin
digestion and subsequently LC-MS/MS analysis was performed for the deep proteome
analysis. The data acquired after the LC-MS/MS analysis were analyzed using
Proteome Discoverer 1.4. The identified peptide matches were validated using
percolator, at less than 1% false discovery rates. RESULTS: A total of 625, 594
and 636 proteins were identified in PACG, POAG and cataract groups, respectively
(n = 9 in each group). The inter-group comparison among all these groups showed
that 246 proteins were identified in all the three groups. An average of 236 +/-
42, 218 +/- 40 and 214 +/- 62 proteins from each AH sample of PACG, POAG and
cataract, respectively, was identified. There were 53 proteins commonly found in
all 9 PACG AH, 59 proteins in POAG AH and 42 proteins in 9 cataracts AH samples.
In the individual analysis, there were 28 proteins found in all the samples
analyzed representing the "constitutive AH proteome." Spectral counting analysis
of 246 proteins identified in all three group types showed significant
differences in protein abundance. In proteins unique to PACG AH, 7 proteins viz.
ARHGEF12, APC2, WAS, PIK3CG, ITGB1, MSN and PFN1 out of 226 were found in
"Regulation of Actin Cytoskeleton" pathway, whereas in POAG 5 out of 206 proteins
viz. ADCY2, ITPR1, MAPK3, MAP3K2 and TUBB1 were found in "Gap Junction" pathway.
CONCLUSIONS: A qualitative as well as a quantitative comparison of proteomes of
AH from PACG, POAG and age-related cataract eyes showed significant differences,
thus providing clues to the disease pathophysiology.
PMID- 29332229
TI - Sociability modifies dogs' sensitivity to biological motion of different social
relevance.
AB - Preferential attention to living creatures is believed to be an intrinsic
capacity of the visual system of several species, with perception of biological
motion often studied and, in humans, it correlates with social cognitive
performance. Although domestic dogs are exceptionally attentive to human social
cues, it is unknown whether their sociability is associated with sensitivity to
conspecific and heterospecific biological motion cues of different social
relevance. We recorded video clips of point-light displays depicting a human or
dog walking in either frontal or lateral view. In a preferential looking
paradigm, dogs spontaneously viewed 16 paired point-light displays showing
combinations of normal/inverted (control condition), human/dog and
frontal/lateral views. Overall, dogs looked significantly longer at frontal human
point-light display versus the inverted control, probably due to its clearer
social/biological relevance. Dogs' sociability, assessed through owner-completed
questionnaires, further revealed that low-sociability dogs preferred the lateral
point-light display view, whereas high-sociability dogs preferred the frontal
view. Clearly, dogs can recognize biological motion, but their preference is
influenced by their sociability and the stimulus salience, implying biological
motion perception may reflect aspects of dogs' social cognition.
PMID- 29332230
TI - A cardioid oscillator with asymmetric time ratio for establishing CPG models.
AB - Nonlinear oscillators are usually utilized by bionic scientists for establishing
central pattern generator models for imitating rhythmic motions by bionic
scientists. In the natural word, many rhythmic motions possess asymmetric time
ratios, which means that the forward and the backward motions of an oscillating
process sustain different times within one period. In order to model rhythmic
motions with asymmetric time ratios, nonlinear oscillators with asymmetric
forward and backward trajectories within one period should be studied. In this
paper, based on the property of the invariant set, a method to design the closed
curve in the phase plane of a dynamic system as its limit cycle is proposed.
Utilizing the proposed method and considering that a cardioid curve is a kind of
asymmetrical closed curves, a cardioid oscillator with asymmetric time ratios is
proposed and realized. Through making the derivation of the closed curve in the
phase plane of a dynamic system equal to zero, the closed curve is designed as
its limit cycle. Utilizing the proposed limit cycle design method and according
to the global invariant set theory, a cardioid oscillator applying a cardioid
curve as its limit cycle is achieved. On these bases, the numerical simulations
are conducted for analyzing the behaviors of the cardioid oscillator. The example
utilizing the established cardioid oscillator to simulate rhythmic motions of the
hip joint of a human body in the sagittal plane is presented. The results of the
numerical simulations indicate that, whatever the initial condition is and
without any outside input, the proposed cardioid oscillator possesses the
following properties: (1) The proposed cardioid oscillator is able to generate a
series of periodic and anti-interference self-exciting trajectories, (2) the
generated trajectories possess an asymmetric time ratio, and (3) the time ratio
can be regulated by adjusting the oscillator's parameters. Furthermore, the
comparison between the simulated trajectories by the established cardioid
oscillator and the measured angle trajectories of the hip angle of a human body
show that the proposed cardioid oscillator is fit for imitating the rhythmic
motions of the hip of a human body with asymmetric time ratios.
PMID- 29332232
TI - Prone position in ARDS: a simple maneuver still underused.
PMID- 29332231
TI - Stage-specific therapeutic strategies of medication-related osteonecrosis of the
jaws: a systematic review and meta-analysis of the drug suspension protocol.
AB - OBJECTIVE: The most debated topic about medication-related osteonecrosis of the
jaws (MRONJ) is its therapy, as there are no definitive guidelines. The aims of
this systematic review were (a) to outline the best therapeutic approach
according to the stage at diagnosis and (b) to perform a meta-analysis to assess
whether the drug-holiday protocol may be or not an effective method in the
management of MRONJ patients. MATERIALS AND METHODS: The systematic review was
performed following the PRISMA principles. Results were screened according to
inclusion and exclusion criteria regarding staging before/after treatment, follow
up, and information provided by the authors. For statistical analysis, linear
variables are reported as means and standard deviations, medians, and inter
quartile range (IQR); normality of data, according to the distribution of
complete healing (primary outcome variable), was assessed with the Kolmogorov
Smirnov test. A p value < 0.05 was considered statistically significant for all
tests. RESULTS: Thirteen studies were selected out of 1480. None of them was case
controlled or randomized. Conservative approach showed good results at early
stages, but heterogeneous result at advanced stages (100% stage 0, stage I range
81-97%, stage II range 63.6-100%, stage III 73%). Surgical approach showed
heterogeneous results at all stages (stage I range 0-100%, stage II range 52
100%, stage III range 50-100%). Statistical analysis showed a significantly
higher prevalence of completely healed sites in patients who followed the drug
holiday protocol. CONCLUSIONS: The results suggest that the current stage
specific approach for MRONJ therapy is based on a sound clinical rationale.
Conservative treatment appears to yield better outcomes at early stages, while
further investigations are needed to elucidate the best protocols for the
management of advanced stages. The drug-holiday protocol statistically promotes
complete healing after oral surgery procedures but the application should be
dictated by the condition of each patient. CLINICAL RELEVANCE: At present, early
MRONJ stages should be primarily treated by means of a conservative approach
while more advanced stages must be carefully evaluated. Individual decisions
should be made for every single case even with respect to the drug-holiday
protocol.
PMID- 29332233
TI - Pilot study of serial FLT and FDG-PET/CT imaging to monitor response to
neoadjuvant chemoradiotherapy of esophageal adenocarcinoma: correlation with
histopathologic response.
AB - OBJECTIVE: The aim of this prospective pilot study was to investigate the
potential of serial FLT-PET/CT compared to FDG-PET/CT to provide an early
indication of esophageal cancer response to concurrent neoadjuvant chemoradiation
therapy. METHODS: Five patients with biopsy-proven esophageal adenocarcinomas
underwent neoadjuvant chemoradiation (Tx) prior to minimally invasive
esophagectomy. The presence of residual tumor was classified histologically using
the Mandard et al. criteria, categorizing patients as pathologic responders and
non-responders. Participants underwent PET/CT imaging 1 h after intravenous
administration of FDG and of FLT on two separate days within 48 h of each other.
Each patient underwent a total of 3 scan "pairs": (1) pre-treatment, (2) during
treatment, and (3) post-treatment. Image-based response to therapy was measured
in terms of changes in SUVmax (DeltaSUV) between pre- and post-therapeutic FLT-
and FDG-PET scans. The PET imaging findings were correlated with the pathology
results after surgery. RESULTS: All tumors were FDG and FLT avid at baseline.
Lesion FLT uptake was lower than with FDG. Neoadjuvant chemoradiation resulted in
a reduction of tumor uptake of both radiotracers in pathological responders (n =
3) and non-responders (n = 2). While the difference in the reduction in mean
tumor FLT uptake during Tx between responders (DeltaSUV = - 55%) and non
responders (DeltaSUV = - 29%) was significant (P = 0.007), for FDG it was not,
[responders had a mean DeltaSUV = - 39 vs. - 31% for non-responders (P = 0.74)].
The difference in the reduction in tumor FLT uptake at the end of treatment
between responders (DeltaSUV = - 62%) and non-responders (DeltaSUV = - 57%) was
not significant (P = 0.54), while for FDG there was a trend toward significance
[DeltaSUV of responders = - 74 vs. - 52% in non-responders (P = 0.06)].
CONCLUSION: The results of this prospective pilot study suggest that early
changes in tumor FLT uptake may be better than FDG in predicting response of
esophageal adenocarcinomas to neoadjuvant chemoradiation. These preliminary
results support the need to corroborate the value of FLT-PET/CT in a larger
cohort.
PMID- 29332234
TI - Attitudes of U.S. Psychiatry Residents and Fellows towards Mental Illness and its
Causes: a Comparison Study with Medical Students.
AB - Stigma towards people with mental illness remains a burden for patients and
healthcare providers. This study at a large US university examined the attitudes
of psychiatry residents and fellows towards mental illness and its causes, and
whether their attitudes differed from the medical student attitudes previously
studied utilizing the same survey method. An electronic questionnaire examining
attitudes toward people with mental illness, causes of mental Illness, and
treatment efficacy was used to survey the attitudes of psychiatry residents and
fellows. Exploratory factor analysis derived from the authors' medical student
survey was used to examine attitudinal factors. The study response rate was 54.2%
(n = 94). Factor analysis employed three factors previously identified reflecting
social acceptance of mental illness, belief in supernatural causes, and belief in
biopsychosocial causes. Residents and fellows reporting more personal experiences
with mental illness, both as a group and when compared with medical students,
were significantly more willing to socialize with the mentally ill. Respondents
who had more professional (work) experience other than medical school or post
graduate training were less likely to believe in supernatural causes of mental
illness. Female residents and fellows were more willing to socialize with the
mentally ill, and were less likely to believe in supernatural causes for mental
illness than their male counterparts. In our study, increased social acceptance
of the mentally ill relates to having personal experiences, advanced training in
psychiatry, and female gender. Both professional experiences outside of training
and female gender reduced the belief in supernatural causes.
PMID- 29332235
TI - Do Diary Studies Cause Behavior Change? An Examination of Reactivity in Sexual
Risk and Substance Use in Young Men Who Have Sex with Men.
AB - Behavioral diaries are frequently used for observing sexual and substance use
behaviors, but participating in diary studies may cause behavior change. This
study examined change in sexual and substance use behaviors among young men who
have sex with men (YMSM) in a two-month diary study compared to control. An
analytic sample of 324 YMSM was randomized to receive daily diaries, weekly
diaries, or no diaries (control) for 2 months. Half of the diary participants
were randomized to receive automated weekly feedback. Between-subjects analyses
found no evidence of change in sexual or substance use behaviors from baseline to
2-month follow-up when comparing the diary conditions to control. Within-persons
growth mixture models of all diary data showed significant decreases in
condomless anal sex (CAS) and illicit drug use. Weekly automated feedback had no
effect on behavior change. Findings provide evidence of change in CAS and illicit
drug use amongst diary participants.
PMID- 29332236
TI - Child Desire Among Men and Women Living with HIV/AIDS in the Traditional Culture
of Vietnam.
AB - In various settings, heterogeneity in fertility rates among HIV-affected couples
highlights the importance of understanding contextual factors to inform program
planning and implementation. We interviewed 1016 patients with HIV/AIDS at seven
clinics in Vietnam to assess their desire to have a(nother) child and willingness
to pay (WTP) for prevention of mother to child transmission (PMTCT) services. One
fifth of participants reported their desire for a(another) child and this was
slightly higher among men than women. Factors associated with the desire to have
a(nother) child of HIV/AIDS patients included (1) not yet have a child or a son,
(2) provincial and district-level service, (3) income per capita, (4) marital
status and (5) history of drug injection. The average WTP for PMTCT service was
US $179 (95% CI 161-197). The study highlights the need for interventions on
social, cultural barriers, improved accessibility and outcomes of counseling, and
better care and treatment services for couples and child affected by HIV/AIDS.
PMID- 29332237
TI - Acute acetaminophen ingestion improves performance and muscle activation during
maximal intermittent knee extensor exercise.
AB - AIM: Acetaminophen is a commonly used medicine for pain relief and emerging
evidence suggests that it may improve endurance exercise performance. This study
investigated some of the physiological mechanisms by which acute acetaminophen
ingestion might blunt muscle fatigue development. METHODS: Thirteen active males
completed 60 * 3 s maximum voluntary contractions (MVC) of the knee extensors
with each contraction separated by a 2 s passive recovery period. This protocol
was completed 60 min after ingesting 1 g of maltodextrin (placebo) or 1 g of
acetaminophen on two separate visits. Peripheral nerve stimulation was
administered every 6th contraction for assessment of neuromuscular fatigue
development, with the critical torque (CT), which reflects the maximal
sustainable rate of oxidative metabolism, taken as the mean torque over the last
12 contractions. Surface electromyography was recorded continuously as a measure
of muscle activation. RESULTS: Mean torque (61 +/- 11 vs. 58 +/- 14% pre-exercise
MVC) and CT (44 +/- 13 vs. 40 +/- 15% pre-exercise MVC) were greater in the
acetaminophen trial compared to placebo (both P < 0.05). Voluntary activation and
potentiated twitch declined at a similar rate in both conditions (P > 0.05).
However, the decline in electromyography amplitude was attenuated in the
acetaminophen trial, with electromyography amplitude being greater compared to
placebo from 210 s onwards (P < 0.05). CONCLUSION: These findings indicate that
acute acetaminophen ingestion might be ergogenic by increasing CT and preserving
muscle activation during high-intensity exercise.
PMID- 29332238
TI - Normal variation in sagittal spinal alignment parameters in adult patients: an
EOS study using serial imaging.
AB - PURPOSE: To describe normal variations in sagittal spinal radiographic parameters
over an interval period and establish physiological norms and guidelines for
which these images should be interpreted. METHODS: Data were prospectively
collected from a continuous series of adult patients with first-episode mild low
back pain presenting to a single institution. The sagittal parameters of two
serial radiographic images taken 6-months apart were obtained with the EOS(r)
slot scanner. Measured parameters include CL, TK, TL, LL, PI, PT, SS, and end and
apical vertebrae. Chi-squared test and Wilcoxon Signed Rank test were used to
compare categorical and continuous variables, respectively. RESULTS: Sixty
patients with a total of 120 whole-body sagittal X-rays were analysed. Mean age
was 52.1 years (SD 21.2). Mean interval between the first and second X-rays was
126.2 days (SD 47.2). Small variations (< 1 degrees ) occur for all except PT
(1.2 degrees ), CL (1.2 degrees ), and SVA (2.9 cm). Pelvic tilt showed
significant difference between two images (p = 0.035). Subgroup analysis based on
the time interval between X-rays, and between the first and second X-rays, did
not show significant differences. Consistent findings were found for end and
apical vertebrae of the thoracic and lumbar spine between the first and second X
rays for sagittal curve shapes. CONCLUSIONS: Radiographic sagittal parameters
vary between serial images and reflect dynamism in spinal balancing. SVA and PT
are predisposed to the widest variation. SVA has the largest variation between
individuals of low pelvic tilt. Therefore, interpretation of these parameters
should be patient specific and relies on trends rather than a one-time
assessment.
PMID- 29332239
TI - Which parameters are relevant in sagittal balance analysis of the cervical spine?
A literature review.
AB - INTRODUCTION: Cervical spine is part of the spine with the most mobility in the
sagittal plane. It is important for surgeons to have reliable, simple and
reproducible parameters to analyse the cervical. MATERIAL AND METHOD: This study
is a systematic review and a critique of current parameters to help improve the
study of cervical spinal balance. We conducted a systematic search of
PUBMED/MEDLINE for literature published since January 2014. Only studies written
in English and containing abstracts were considered for inclusion. The search
performed was: "C7 slope" OR "T1 slope" OR "C2C7 offset" OR "C2C7 lordosis" OR
"cervical SVA (sagittal vertical axis)" OR "TIA (thoracic inlet angle)" (Lee et
al., J Spinal Disord Tech 25(2):E41-E47, 2012) OR "SCA (spino-cranial angle)".
Exclusion criteria were purely post-operative and cadaveric analysis, studies
performed with CT scan or MRI, studies on adolescent idiopathic scoliosis,
traumatology studies and no standing analysis of the cervical spine. Relevance
was confirmed by investigators if cervical parameters was a major criteria of the
study. RESULTS: 138 articles were found by the electronic search. After complete
evaluation 20 articles were selected. The large majority of papers used the same
parameters C2_C7 lordosis, C2-C7 SVA, T1 slope or C7 slope and T1 slope/cervical
lordosis mismatch. Janusz reported a new parameter using a retrospective cohort
of patient with cervical radiculopathy: the TIA (thoracic inlet angle). Le Huec
reported an other new parameter based on a prospective study of asymptomatic
volunteer: the spino-cranial angle (SCA). This parameter is highly correlated
with the C7 slope and the cervical lordosis. Other studies reported parameters
that are more global balance analysis including the cervical spine than cervical
spine balance itself. CONCLUSION: The most important parameters to analyse the
cervical sagittal balance according to the literature available today for good
clinical outcomes are the following: C7 or T1 slope, average value 20 degrees ,
must not be higher than 40 degrees . cSVA must not be less than 40 degrees C
(mean value 20 mm). SCA (spine cranial angle) must stay in a norm (83 degrees +/
9 degrees ). Future studies should focus on those three parameters to analyse
and compare pre and post op data and to correlate the results with the quality of
life improvement.
PMID- 29332240
TI - Preperitoneal closed-system suction drainage after totally extraperitoneal
hernioplasty in the prevention of early seroma formation: a prospective double
blind randomised controlled trial.
AB - OBJECTIVES: Seroma is a virtually unavoidable early sequela after TEP
hernioplasty. This randomised controlled trial evaluated the outcomes of
preperitoneal closed-system suction drainage in laparoscopic totally
extraperitoneal (TEP) hernioplasty for inguinal hernia. METHODS: Ninety patients
aged 18-80 years who presented to our hospital between May 2016 and February 2017
with primary unilateral inguinal hernia were randomised into the preperitoneal
drain and no-drain groups. The primary outcome was seroma size on postoperative
day 6. Secondary outcomes included clinical seroma formation and seroma size on
day 1, day 6, 1 and 7 months postoperatively, length of postoperative stay, pain
score, and recurrence. RESULTS: There was no significant difference in age, sex,
co-morbidities, hernia side, mean hernia size, operating time, fixation adjuncts,
or postoperative stay. The overall incidence of clinical seroma formation was
25.6% on postoperative day 1, 60.3% on postoperative day 6, 13.2% 1 month and 0%
7 months postoperatively. The mean drain output was 57.9 ml. The drain group had
significantly fewer patients with seroma on day 1 (6 vs 14, p = 0.022) and day 6
(17 vs 30, p = 0.000), and a smaller mean seroma size on days 1 and 6 (p =
0.000). Subgroup analysis showed that sac ligation versus reduction, peritoneal
perforation, and fixation adjuncts had no significant effects on seroma formation
or size. There is a trend of lower early post-operation VAS score and more
urinary retention in drain group was observed but not reaching statistical
significance. No differences in postoperative pain score or complications were
observed at 1 and 7 months' post operation. CONCLUSIONS: Preperitoneal drainage
for 23 h after laparoscopic TEP hernioplasty for inguinal hernia can effectively
decrease seroma formation in the early postoperative period, and potentially
improving postoperative pain. The benefit is short-term and no significant
difference was demonstrated after 1-month post operations. This tradition
technique applied to novel operative repair of inguinal hernia is safe and
feasible with no significant morbidity demonstrated. Preperitoneal drainage after
TEP can be considered as an option to improve patient satisfactions and recovery
in selected patient group for maximal benefit, especially for those with
prolonged operation which may associate with higher chance of seroma formation.
PMID- 29332241
TI - Atrial fibrillation is associated with sudden cardiac death: a systematic review
and meta-analysis.
AB - PURPOSE: Recent studies suggest that atrial fibrillation (AF) is associated with
increased cardiovascular risk and mortality including sudden cardiac death (SCD).
According to the Cardiovascular Heath Study cohort, the incident rate of SCD was
higher in the AF population (2.9 per 1000 per year) compared with non-AF controls
(1.3 per 1000 per year). In this study, we performed a systematic review and meta
analysis to explore the association between AF and SCD. METHODS: We
comprehensively searched the databases of MEDLINE and EMBASE from inception to
January 2017. Included studies were published prospective or retrospective cohort
studies that compared the risk of developing SCD, defined by World Health
Organization's criteria, in AF patients versus non-AF patients. Data from each
study were combined using the random-effects, generic inverse variance method of
DerSimonian and Laird to calculate the risk ratios and 95% confidence intervals.
RESULTS: Twenty-seven studies from January 1991 to February 2017 involving 8401
AF patients and 67,608 non-AF controls were included in this meta-analysis.
Compared with controls, AF patients had a significantly higher risk of SCD in
overall analysis (pooled risk ratio = 2.04, 95% confidence interval: 1.77-2.35, p
< 0.01, I2 = 42.66) as well as subgroups of general population studies, previous
myocardial infarction or coronary artery disease, heart failure, hypertrophic
cardiomyopathy (HCM), Brugada syndrome, and patients with either a pacemaker or
implantable cardioverter defibrillator (ICD). In subgroup analysis of
multivariate-adjusted studies, AF also had a significantly higher risk of SCD
(pooled risk ratio = 2.22, 95% confidence interval = 1.59-3.09, p < 0.01, I2 =
73.95). Incident rate of SCD in AF was 2-fold higher than controls but not
statistically significant (pooled rate ratio = 2.06, 95% confidence interval =
0.66-7.53, p = 0.292, I2 = 88.58). CONCLUSIONS: Our meta-analysis demonstrates a
statistically significant increased risk of SCD with AF in the general population
and in those with previous myocardial infarction, coronary artery disease, heart
failure, HCM, Brugada syndrome, and an implanted rhythm device.
PMID- 29332242
TI - Selective IKK2 inhibitor IMD0354 disrupts NF-kappaB signaling to suppress corneal
inflammation and angiogenesis.
AB - Corneal neovascularization is a sight-threatening condition caused by
angiogenesis in the normally avascular cornea. Neovascularization of the cornea
is often associated with an inflammatory response, thus targeting VEGF-A alone
yields only a limited efficacy. The NF-kappaB signaling pathway plays important
roles in inflammation and angiogenesis. Here, we study consequences of the
inhibition of NF-kappaB activation through selective blockade of the IKK complex
IkappaB kinase beta (IKK2) using the compound IMD0354, focusing on the effects of
inflammation and pathological angiogenesis in the cornea. In vitro, IMD0354
treatment diminished HUVEC migration and tube formation without an increase in
cell death and arrested rat aortic ring sprouting. In HUVEC, the IMD0354
treatment caused a dose-dependent reduction in VEGF-A expression, suppressed
TNFalpha-stimulated expression of chemokines CCL2 and CXCL5, and diminished actin
filament fibers and cell filopodia formation. In developing zebrafish embryos,
IMD0354 treatment reduced expression of Vegf-a and disrupted retinal
angiogenesis. In inflammation-induced angiogenesis in the rat cornea, systemic
selective IKK2 inhibition decreased inflammatory cell invasion, suppressed CCL2,
CXCL5, Cxcr2, and TNF-alpha expression and exhibited anti-angiogenic effects such
as reduced limbal vessel dilation, reduced VEGF-A expression and reduced
angiogenic sprouting, without noticeable toxic effect. In summary, targeting NF
kappaB by selective IKK2 inhibition dampened the inflammatory and angiogenic
responses in vivo by modulating the endothelial cell expression profile and
motility, thus indicating an important role of NF-kappaB signaling in the
development of pathologic corneal neovascularization.
PMID- 29332243
TI - Photosystem I with benzoquinone analogues incorporated into the A1 binding site.
AB - Time-resolved FTIR difference spectroscopy has been used to study photosystem I
(PSI) particles with three different benzoquinones [plastoquinone-9 (PQ), 2,6
dimethyl-1,4-benzoquinone (DMBQ), 2,3,5,6-tetrachloro-1,4-benzoquinone (Cl4BQ)]
incorporated into the A1 binding site. If PSI samples are cooled in the dark to
77 K, the incorporated benzoquinones are shown to be functional, allowing the
production of time-resolved (P700+A1--P700A1) FTIR difference spectra. If samples
are subjected to repetitive flash illumination at room temperature prior to
cooling, however, the time-resolved FTIR difference spectra at 77 K display
contributions typical of the P700 triplet state (3P700), indicating a loss of
functionality of the incorporated benzoquinones, that occurs because of double
protonation of the incorporated benzoquinones. The benzoquinone protonation
mechanism likely involves nearby water molecules but does not involve the
terminal iron-sulfur clusters FA and FB. These results and conclusions resolve
discrepancies between results from previous low-temperature FTIR and EPR studies
on similar PSI samples with PQ incorporated.
PMID- 29332244
TI - Structural insights into the function of Elongator.
AB - Conserved from yeast to humans, Elongator is a protein complex implicated in
multiple processes including transcription regulation, alpha-tubulin acetylation,
and tRNA modification, and its defects have been shown to cause human diseases
such as familial dysautonomia. Elongator consists of two copies of six core
subunits (Elp1, Elp2, Elp3, Elp4, Elp5, and Elp6) that are organized into two
subcomplexes: Elp1/2/3 and Elp4/5/6 and form a stable assembly of ~ 850 kDa in
size. Although the catalytic subunit of Elongator is Elp3, which contains a
radical S-adenosyl-L-methionine (SAM) domain and a putative histone
acetyltransferase domain, the Elp4/5/6 subcomplex also possesses ATP-modulated
tRNA binding activity. How at the molecular level, Elongator performs its
multiple functions and how the different subunits regulate Elongator's activities
remains poorly understood. Here, we provide an overview of the proposed functions
of Elongator and describe how recent structural studies provide new insights into
the mechanism of action of this multifunctional complex.
PMID- 29332246
TI - An historical perspective of the discovery of titin filaments -Part 2.
AB - In 2017, a Special Issue of Biophysical Reviews was devoted to "Titin and Its
Binding Partners. The issue contained a review: "An historical perspective of the
discovery of titin filaments" by dos Remedios and Gilmour that was intended to be
a history of the discovery of the giant protein titin, previously named
connectin. The review took readers back to the earliest discovery of the so
called third filament component of skeletal and cardiac muscle sarcomeres and
ended in 1969. Recently, my colleague Shin'ichi Ishiwata gently reminded me of
two papers published in 1990 and 1993 that were unwittingly omitted from the
original historical perspective. In the first paper (J Cell Biol 110:53-62,
1990), Funatsu et al. examined the elastic filaments in skeletal muscle using a
combination of light and electron microscopy, but they also measured resting as
well as passive stiffness mechanical measurements to establish that connectin
(titin) is responsible for both stiffness and fiber tension. In the second paper
(J Cell Biol 120:711-724, 1993), Funatsu et al. used permeabilised cardiac muscle
myocytes (from rabbit papillary muscles) and focussed on filament ultrastructure
using either freeze-substitution or deep-etched replica methods to visualise
connectin/titin filaments in fibers with and without actin and myosin filaments.
PMID- 29332247
TI - Practical advantages of contrast-enhanced ultrasound in abdominopelvic radiology.
AB - Computed tomography (CT) and magnetic resonance imaging (MRI) are two of the
workhorse modalities of abdominopelvic radiology. However, these modalities are
not without patient- and technique-specific limitations that may prevent a timely
and accurate diagnosis. Contrast-enhanced ultrasound (CEUS) is an effective,
rapid, and cost-effective imaging modality with expanding clinical utility in the
United States. In this pictorial essay, we provide a case-based discussion
demonstrating the practical advantages of CEUS in evaluating a variety of
pathologies in which CT or MRI was precluded or insufficient. Through these
advantages, CEUS can serve a complementary role with CT and MRI in comprehensive
abdominopelvic radiology.
PMID- 29332245
TI - Reprogramming the metabolome rescues retinal degeneration.
AB - Metabolomics studies in the context of ophthalmology have largely focused on
identifying metabolite concentrations that characterize specific retinal
diseases. Studies involving mass spectrometry (MS) and nuclear magnetic resonance
(NMR) spectroscopy have shown that individuals suffering from retinal diseases
exhibit metabolic profiles that markedly differ from those of control
individuals, supporting the notion that metabolites may serve as easily
identifiable biomarkers for specific conditions. An emerging branch of
metabolomics resulting from biomarker studies, however, involves the study of
retinal metabolic dysfunction as causes of degeneration. Recent publications have
identified a number of metabolic processes-including but not limited to glucose
and oxygen metabolism-that, when perturbed, play a role in the degeneration of
photoreceptor cells. As a result, such studies have led to further research
elucidating methods for prolonging photoreceptor survival in an effort to halt
degeneration in its early stages. This review will explore the ways in which
metabolomics has deepened our understanding of the causes of retinal degeneration
and discuss how metabolomics can be used to prevent retinal degeneration from
progressing to its later disease stages.
PMID- 29332248
TI - Performance of diffusion-weighted magnetic resonance imaging at 3.0T for early
assessment of tumor response in locally advanced rectal cancer treated with
preoperative chemoradiation therapy.
AB - PURPOSE: The purpose of the article is to determine whether changes in apparent
diffusion coefficient (ADC) values of locally advanced rectal cancer (LARC)
obtained 2 weeks after the beginning of chemoradiation therapy (CRT) allow to
predict treatment response and whether correlate with tumor histopathologic
response. METHODS: Forty-three patients receiving CRT for LARC and 3.0T magnetic
resonance imaging with diffusion-weighted sequences before treatment, 2 weeks
during, and 8 weeks post the completion of CRT were included. ADC values were
calculated at each time point and percentage of ADC changes at 2 weeks (DeltaADC
during) and 8 weeks (DeltaADC post) were assessed. Data were correlated to
surgical results and histopathologic tumor regression grade (TRG), according to
Mandard's classification. ADC values and DeltaADCs of complete responders (CR;
TRG1) and non-complete responders (non-CR; TRG 2-5) were compared. Receiver
operating characteristic curve (ROC) analysis was used to assess diagnostic
accuracy of DeltaADC for differentiating CR from non-CR. The correlation with TRG
was investigated using Spearman's rank test. RESULTS: DeltaADC during and
DeltaADC post were significantly higher in CR (33.9% and 57%, respectively)
compared to non-CR (13.5% and 2.2%, respectively) group (p = 0.006 and p < 0.001,
respectively). ROC analysis revealed the following diagnostic performances:
DeltaADC during: AUC 0.78 (0.08), p = 0.004, cut-off 20.6% (sensitivity 75% and
specificity 76.5%); DeltaADC post: AUC 0.94 (0.04), p <= 0.001, cut-off 22%
(sensitivity 95% and specificity 82.4%). Significant moderate and good negative
correlation was found between DeltaADC during and DeltaADC post and TRG (r = -
0.418, p = 0.007; r = - 694, p <= 0.001, respectively). CONCLUSION: DeltaADC at 2
weeks after the beginning of CRT is a reliable tool to early assess treatment
response.
PMID- 29332249
TI - Correlation of flow density, as measured using optical coherence tomography
angiography, with structural and functional parameters in glaucoma patients.
AB - PURPOSE: To evaluate the correlation between flow density, as measured by optical
coherence tomography angiography (OCTA), and structural and functional parameters
in patients with open-angle glaucoma. METHODS: Thirty-four eyes of 34 patients
with open-angle glaucoma and 35 eyes of 35 healthy subjects were prospectively
included in this study. OCTA was performed using RTVue XR Avanti with AngioVue.
The macula was imaged with a 3 * 3 mm scan and the optic nerve head (ONH) with a
4.5 * 4.5 mm scan. Visual field parameters [mean deviation (MD), pattern standard
deviation (PSD) and visual field index (VFI)], Bruch's membrane opening minimal
rim width (BMO-MRW), retinal nerve fiber layer thickness (RNFLT) and the
stereometric parameters rim area, cup/disc area (HRT III, Heidelberg Retina
Tomograph, Heidelberg Engineering) were tested for correlation with flow density
data. RESULTS: The flow density (whole en face) in the retinal OCT angiograms
(superficial: p = 0.01; deep: p = 0.005), in the radial peripapillary capillary
network (p < 0.001) and in the OCT angiograms of the optic nerve head (p = 0.004)
were significantly lower in the glaucoma group when compared with the control
group. The flow density in the RPC network correlated significantly with all
functional and structural parameters tested. The strongest correlation was found
between the RPC flow density (inside disc) and the BMO-MRW (Spearman's
correlation coefficient = 0.912, p < 0.001). CONCLUSIONS: Glaucoma patients
showed a reduced ONH and macular perfusion when compared with healthy controls.
The flow density as measured by OCTA correlated with structural damage and visual
field loss in glaucoma patients. Non-invasive quantitative analyses of flow
density using OCTA provide a new parameter describing a different aspect of
glaucoma, which could be useful in clinical practice.
PMID- 29332250
TI - The levels of 12 cytokines and growth factors in tears: hyperthyreosis vs
euthyreosis.
AB - PURPOSE: Simultaneous analyses of the contents and ratios of 12 cytokines and
growth factors in single samples of human tears were performed, and the results
were compared between a group of healthy subjects and a group of patients with
Graves' hyperthyreosis (GH) without thyroid-associated orbitopathy (TAO).
METHODS: Determinations and concentration measurements of interleukins (IL-2,
IL4, IL-6, IL-8, IL-10, IL-1alpha, and IL-1beta) interferon (IFN-gamma), tumor
necrosis factor (TNF-alpha), monocyte chemoattractant protein (MCP-1), vascular
endothelial growth factor (VEGF), and epidermal growth factor (EGF) were
performed with single tear samples from 21 patients with hyperthyreosis and 22
healthy subjects. The analyses were performed using a Randox microchip with an
Evidence Biochip Array Analyzer. RESULTS: We found significant differences
between the healthy donor group and the hyperthyreosis group in the levels of IL
6, IL-10, VEGF, IL-1alpha, and MCP-1. The concentration of IL-6 was considerably
higher in the hyperthyreosis group, IL-10 was higher in the healthy donor group,
and VEGF and MPC-1 were higher in the hyperthyreosis group. The IL-8 and IFN
gamma levels were higher in the hyperthyreosis group. The ratios of all of the
cytokines to anti-inflammatory IL-10 were significantly elevated in the
hyperthyreosis group. CONCLUSION: There are clear differences in the levels of
cytokines and growth factors in the tears of healthy subjects and patients with
GH without TAO. Tear cytokine changes and related dysfunctional tear syndrome
(DTS) could be an early sign of occult TAO in Graves' hyperthyreosis patients.
PMID- 29332251
TI - Clinical Pharmacokinetics and Pharmacodynamics of Telavancin Compared with the
Other Glycopeptides.
AB - Telavancin was discovered by modifying the chemical structure of vancomycin and
belongs to the group of lipoglycopeptides. It employs its antimicrobial potential
through two distinct mechanisms of action: inhibition of bacterial cell wall
synthesis and induction of bacterial membrane depolarization and
permeabilization. In this article we review the clinically relevant
pharmacokinetic and pharmacodynamic data of telavancin. For comparison, the
pharmacokinetic and pharmacodynamic data of the other glycopeptides are
presented. Although, in contrast to the newer lipoglycopeptides, telavancin
demonstrates a relatively short half-life and rapid total clearance, its apparent
volume of distribution (Vd) is almost identical to that of dalbavancin. The
accumulation of telavancin after repeated dosing is only marginal, whereas the
pharmacokinetic values of the other glycopeptides show much greater differences
after administration of multiple doses. Despite its high plasma-protein binding
of 90% and relatively low Vd of approximately 11 L, telavancin shows near
complete equilibration of the free fraction in plasma with soft tissue. The ratio
of the area under the plasma concentration-time curve from time zero to 24 h
(AUC24) of unbound plasma concentrations to the minimal inhibitory concentration
(MIC) required to inhibit growth of 90% of organisms (MIC90) of Staphylococcus
aureus and S. epidermidis of telavancin are sufficiently high to achieve
pharmacokinetic/pharmacodynamic targets indicative for optimal bacterial killing.
Considering both the AUC24/MIC ratios of telavancin and the near complete
equilibration of the free fraction in plasma with soft tissue, telavancin is an
appropriate antimicrobial agent to treat soft tissue infections caused by Gram
positive pathogens. Although the penetration of telavancin into epithelial lining
fluid (ELF) requires further investigations, the AUC24/MIC ratio for S. aureus
indicates that bactericidal activity in the ELF could be expected.
PMID- 29332253
TI - How to attract talented juniors to urogynaecology.
PMID- 29332252
TI - A review of the impact of pregnancy and childbirth on pelvic floor function as
assessed by objective measurement techniques.
AB - The objective of this narrative review is to study the impact of pregnancy and
childbirth on pelvic floor function as assessed by objective measurement
techniques with quantitative data carried out during pregnancy and after
childbirth. A literature search in MEDLINE and relevant and up-to-date journals
from 1960 until April 2017 was performed for articles dealing with the impact of
pregnancy and childbirth on pelvic floor function as assessed by objective
measurement methods. Only studies describing objective measurement techniques.
i.e., urodynamics, ultrasound (US), magnetic resonance imaging (MRI), Pelvic
Organ Prolapse Quantification (POP-Q) system, and neurophysiologic tests carried
out throughout pregnancy and after childbirth are included. Relevant studies
presenting objective quantitative data are analyzed and briefly summarized. The
number of studies meeting selection criteria was relatively few. Pregnancy,
especially first pregnancy, is associated bladder neck lowering, increased
bladder neck mobility, pelvic organ descent, decreased levator ani strength, and
decreased urethral resistance. These changes are accentuated after vaginal
delivery. Data on the impact of obstetrical and neonatal variables are transient
and seem of less importance. Cesarean delivery is not completely protective. In
most women, pelvic floor muscle function recovers in the year after delivery.
Objective measurement techniques during pregnancy may allow identification of
women susceptible to pelvic floor dysfunction later in life and offer the
opportunity for counseling and preventive treatment strategies.
PMID- 29332255
TI - Profiling attention and cognition enhancing drugs in a rat touchscreen-based
continuous performance test.
AB - RATIONALE: A novel rodent continuous performance test (CPT) was developed as one
of the goals of the NEWMEDS (Novel Methods leading to New Medications in
Depression and Schizophrenia) consortium to improve its translatability to the
CPT test used in human subjects. OBJECTIVES: The objective of the study is to
investigate the effects of attention and cognition enhancing drugs in rodent CPT.
METHODS: A single cohort of rats were trained to asymptotic performance in the
test. Pharmacological test sessions were then performed twice per week in a full
crossover design with the following drugs tested: methylphenidate (0.3, 1, and 3
mg/kg), the alpha4beta2 nicotinic agonist ABT-594 (0.0023, 0.007 and 0.023
mg/kg), modafinil (8, 16, and 32 mg/kg), atomoxetine (0.3, 1, and 3 mg/kg),
donepezil (0.1, 0.3, and 1 mg/kg), and memantine (1.25, 2.5, and 5 mg/kg).
RESULTS: The stimulant-like drugs methylphenidate, ABT-594, and modafinil were
found to increase measures of impulsivity and overall responding with generally
no positive effects on d', a putative measure of attention, with the exception of
ABT-594 which improved d' at the highest dose tested. Atomoxetine and the memory
enhancing drugs donepezil and memantine, on the other hand, were found to reduce
measures of impulsivity and responding and had either negligible or worsening
effects on d'. CONCLUSIONS: Our results suggest rodent CPT can detect changes in
impulsivity resulting from drugs known to improve attention in rodents and
humans. However, additional work is needed to assess the sensitivity and validity
of this assay for assessing effects on attention.
PMID- 29332254
TI - Comparison of adjustable continence therapy periurethral balloons and artificial
urinary sphincter in female patients with stress urinary incontinence due to
intrinsic sphincter deficiency.
AB - INTRODUCTION AND HYPOTHESIS: The objective was to compare the outcomes of the
ACT(r) device with those of the artificial urinary sphincter (AUS) AMS 800 in the
treatment of stress urinary incontinence (SUI) due to sphincter deficiency in
women. METHODS: All the women who underwent surgical treatment for SUI due to
intrinsic sphincter deficiency from 2007 to 2017 were included in a single-center
retrospective study. The primary endpoint was the functional outcome.
Perioperative functional parameters of the two groups were compared. RESULTS:
Twenty-five patients underwent an ACT(r) implantation and 36 an AUS implantation.
Patients in the AUS group were younger (62.9 vs 70.4 years; p = 0.03) with less
comorbidity (ASA Score = 3 in 12.1% vs 33.3%; p = 0.005). Operative time and
hospital stay were shorter in the ACT(r) group (45.7 vs 206.1 min; p < 0.001; 1.7
vs 7 days; p < 0.001 respectively). There was a higher rate of intraoperative
complications in the AUS group (47% vs 8%; p < 0.001) but the rates of
postoperative complications were similar between both groups. The ACT(r) was
associated with an increased risk of urinary retention (20% vs 2.8%; p = 0.04).
Results were in favor of AUS for: decrease in USP stress incontinence subscore (
7.6 vs -3.2; p < 0.001), number of pads per 24 h (- 4.6 vs -2.3; p = 0.002), PGII
scale (PGII = 1: 61.1% vs 12%; p < 0.001), and cure rate (71.4% vs 21.7%; p <
0.001). CONCLUSIONS: In the present series, keeping in mind the significantly
different baseline characteristics, AUS implantation was associated with better
functional outcomes than the ACT(r) in female patients with SUI due to intrinsic
sphincter deficiency, but with a higher intraoperative complications rate, longer
operative time, and a longer stay.
PMID- 29332256
TI - Dopamine-dependent social information processing in non-human primates.
AB - RATIONALE: Dopamine (DA) is a neurotransmitter whose roles have been suggested in
various aspects of brain functions. Recent studies in rodents have reported its
roles in social function. However, how DA is involved in social information
processing in primates has largely remained unclear. OBJECTIVES: We investigated
prefrontal cortical (PFC) activities associated with social vs. nonsocial visual
stimulus processing. METHODS: Near-infrared spectroscopy (NIRS) was applied to
Japanese macaques, along with pharmacological manipulations of DA transmission,
while they were gazing at social and nonsocial visual stimuli. RESULTS:
Oxygenated (oxy-Hb) and deoxygenated (deoxy-Hb) hemoglobin changes as well as
functional connectivity based on such Hb changes within the PFC network which
were distinct between social and nonsocial stimuli were observed. Administration
of both D1 and D2 receptor antagonists affected the Hb changes associated with
social stimuli, whereas D1, but not D2, receptor antagonist affected the Hb
changes associated with nonsocial stimuli. CONCLUSIONS: These results suggest
that mesocortical DA transmission in the PFC plays significant roles in social
information processing, which involves both D1 and D2 receptor activation, in
nonhuman primates. However, D1 and D2 receptor signaling in the PFC mediates
different aspects of social vs. nonsocial information processing.
PMID- 29332259
TI - Nobel Prizes 2017 and their impact for physiology.
PMID- 29332257
TI - Kynurenic acid and its derivatives are able to modulate the adhesion and
locomotion of brain endothelial cells.
AB - The neuroprotective actions of kynurenic acid (KYNA) and its derivatives in
several neurodegenerative disorders [characterized by damage to the cerebral
endothelium and to the blood-brain barrier (BBB)] are well established. Cell
extracellular matrix (ECM) adhesion is supposedly involved in recovery of
impaired cerebral endothelium integrity (endothelial repair). The present work
aimed to investigate the effects of KYNA and its synthetic derivatives on
cellular behaviour (e.g. adhesion and locomotion) and on morphology of the GP8
rat brain endothelial cell line, modeling the BBB endothelium. The effects of
KYNA and its derivatives on cell adhesion were measured using an impedance-based
technique, the xCELLigence SP system. Holographic microscopy (HolomonitorTM M4)
was used to analyse both chemokinetic responses and morphometry. The GP8 cells
proved to be a suitable model cell line for investigating cell adhesion and the
locomotion modulator effects of kynurenines. KYNA enhanced cell adhesion and
spreading, and also decreased the migration/motility of GP8 cells at
physiological concentrations (10-9 and 10-7 mol/L). The derivatives containing an
amide side-chain at the C2 position (KYNA-A1 and A2) had lower adhesion inducer
effects compared to KYNA. All synthetic analogues (except KYNA-A5) had a time
dependent inhibitory effect on GP8 cell adhesion at a supraphysiological
concentration (10-3 mol/L). The immobilization promoting effect of KYNA and the
adhesion inducer activity of its derivatives indicate that these compounds could
contribute to maintaining or restoring the protective function of brain
endothelium; they also suggest that cell-ECM adhesion and related cell responses
(e.g. migration/motility) could be potential new targets of KYNA.
PMID- 29332258
TI - Photodynamic antimicrobial chemotherapy (PACT) using toluidine blue inhibits both
growth and biofilm formation by Candida krusei.
AB - Among non-albicans Candida species, the opportunistic pathogen Candida krusei
emerges because of the high mortality related to infections produced by this
yeast. The Candida krusei is an opportunistic pathogen presenting an intrinsic
resistance to fluconazol. In spite of the reduced number of infections produced
by C. krusei, its occurrence is increasing in some groups of patients submitted
to the use of fluconazol for prophylaxis. Photodynamic antimicrobial chemotherapy
(PACT) is a potential antimicrobial therapy that combines visible light and a
nontoxic dye, known as a photosensitizer, producing reactive oxygen species (ROS)
that can kill the treated cells. The objective of this study was to investigate
the effects of PACT, using toluidine blue, as a photosensitizer on both growth
and biofilm formation by Candida krusei. In this work, we studied the effect of
the PACT, using TB on both cell growth and biofilm formation by C. krusei. PACT
was performed using a light source with output power of 0.068 W and peak
wavelength of 630 nm, resulting in a fluence of 20, 30, or 40 J/cm2. In addition,
ROS production was determined after PACT. The number of samples used in this
study varied from 6 to 8. Statistical differences were evaluated by analysis of
variance (ANOVA) and post hoc comparison with Tukey-Kramer test. PACT inhibited
both growth and biofilm formation by C. krusei. It was also observed that PACT
stimulated ROS production. Comparing to cells not irradiated, irradiation was
able to increase ROS production in 11.43, 6.27, and 4.37 times, in the presence
of TB 0.01, 0.02, and 0.05 mg/mL, respectively. These results suggest that the
inhibition observed in the cell growth after PACT could be related to the ROS
production, promoting cellular damage. Taken together, these results demonstrated
the ability of PACT reducing both cell growth and biofilm formation by C. krusei.
PMID- 29332260
TI - Prostate cancer rates in patients with initially negative elastography-targeted
biopsy vs. systematic biopsy.
AB - PURPOSE: To assess whether real-time elastography-targeted biopsy (RTE-bx) is
superior to the standard systematic transrectal ultrasound (TRUS)-guided biopsy
in predicting subsequent prostate cancer (PCa) rates in patients with initially
negative biopsy and to specifically reveal differences in the occurrence of high
grade (Gleason >= 4 + 3) PCa by comparing both biopsy methods. PATIENTS AND
METHODS: Overall, 630 patients had an initially negative prostate biopsy between
2007 and 2015, either RTE targeted (n = 213) or systematically (n = 417). Follow
up data, ascertained by a questionnaire, of patients receiving RTE-bx were
compared to data of patients receiving systematic biopsy (sbx) using Mann-Whitney
U test and Chi-square test. We performed logistic regression analyses to assess
any association with PCa or high-grade PCa occurrence. RESULTS: In total, 258
(41%) patients were diagnosed with PCa at repeat biopsy whereof 54 (8.6%)
harboured high-grade PCa. PCa occurred in 95 (44.6%) patients with initially
negative RTE-bx and in 163 (39.1%) patients with initially negative sbx (p =
0.003). 24 (11.3%) patients receiving RTE-bx and 30 (7.2%) patients receiving sbx
were diagnosed with high-grade PCa (p = 0.095). Logistic regression analyses
showed that patients with the initial RTE-bx vs. those with the initial sbx
neither resulted in a significant higher risk for PCa occurrence (OR 1.35 [CI
0.87-2.1]; p = 0.2) nor for high-grade PCa occurrence (OR 1.52 [CI 0.66-3.35]; p
= 0.3). CONCLUSIONS: We found no statistically significant association of prior
biopsy method to subsequent PCa or high-grade PCa occurrence. Referring to our
analyses, RTE is not superior to sbx in predicting subsequent PCa rates and,
therefore, not eligible to decide on repeat biopsy.
PMID- 29332261
TI - Is the laser mightier than the sword? A comparative study for the urethrotomy.
AB - PURPOSE: The knife is the most common used instrument for endoscopic urethrotomy.
Unfortunately, there are high recurrence rates; it is thought that a laser
reduces those rates. We compared the two techniques in this retrospective study.
MATERIALS AND METHODS: Between 2010 and 2014, 127 patients were operated on with
the knife (KG) and for 65 patients, the laser (LG) was used. We scored the
complexity of the stricture using the UREThRAL stricture score (USS) and we
scored if a treatment was successful. A failure was determined as recurrence, but
also starting clean intermittent catheterization was stated as failure. RESULTS:
There was no difference in USS between the two groups (KG: 5.7 vs LG: 6.0); the
laser was more often used in a patient with a recurrence stricture (25.2 vs
43.1%). No difference was found in postoperative increase in flow-rate (9.5 vs
10.5 ml/sec), the number of complications (all Clavien I and one Clavien III in
the KG) or the failure rate (58.3 vs 68.8%). When looked separately at patients
treated for primary stricture and for a recurrence (96.7 vs 91.2%), no
differences were found. CONCLUSION: There were no significant differences between
knife and laser. With costs taken in consideration, we would advise treatment
with the knife. Our results also show a high failure rate, especially in the
recurrence group. Therefore, in case of recurrence, an open reconstruction should
be considered.
PMID- 29332263
TI - Creating a Primary Care Workforce: Strategies for Leaders, Clinicians, and
Nurses.
AB - Many primary care clinics struggle with rapid implementation and systematic
expansion of primary care behavioral health (PCBH) services. Often, an uneven
course of program development is due to lack of attention to preparing clinic
leadership, addressing operational factors, and training primary care providers
(PCPs) and nurses. This article offers competency tools for clinic leaders, PCPs,
and nurses to use in assessing their status and setting change targets. These
tools were developed by researchers working to disseminate evidence-based
interventions in primary care clinics that included fully integrated behavioral
health consultants and were then used by early adaptors of the PCBH model. By
deploying these strategies, both practicing and teaching clinics will take a big
step forward in developing the primary care workforce needed for primary care
teams, where the behavioral health needs of a patient of any age can be addressed
at the time of need.
PMID- 29332262
TI - Tumor expression of survivin, p53, cyclin D1, osteopontin and fibronectin in
predicting the response to neo-adjuvant chemotherapy in children with advanced
malignant peripheral nerve sheath tumor.
AB - PURPOSE: Selected cell-cycle regulators and extracellular matrix proteins were
found to play roles in malignant peripheral nerve sheath tumor (MPNST) biology.
We aimed to analyze whether initial tumor tissue expressions of survivin, p53,
cyclin D1, osteopontin (OPN) and fibronectin (FN) correlate with the response to
neo-adjuvant CHT (naCHT) in children with advanced inoperable MPNST. METHODS: The
study included 26 children with MPNST (M/F 14/12, median age 130 months) treated
in Polish centers of pediatric oncology between 1992 and 2013. Tissue expression
of markers was studied immunohistochemically in the manually performed tissue
microarrays and assessed semi-quantitatively as low and high, based on the rate
of positive cells and staining intensity. RESULTS: Good response to naCHT was
noted in 47.6%, while poor-in 52.4% of patients. The response to naCHT was
influenced negatively by the presence of neurofibromatosis NF1 and high initial
tumor tissue expression of OPN, survivin, p53 and cyclin D1. Patients with high
tumor expression of either OPN, survivin or p53 and those with simultaneous high
expression of >= 3 of the markers, responded significantly worse to naCHT, than
patients, in whom expression of <= 2 markers were detected at diagnosis. Nearly,
85% of patients expressing >= 3 markers, responded poor to CHT; while 87.5% of
children, expressing <= 2 markers, were good responders. CONCLUSION: The initial
tumor tissue expression of OPN, survivin, p53 and cyclin D1 may serve as markers
to predict response to naCHT in pediatric advanced MPNST. Future studies in more
numerous group of patients are needed to confirm these preliminary results.
PMID- 29332264
TI - The Role of Affect and Coping in Diabetes Self-Management in Rural Adults with
Uncontrolled Diabetes and Depressive Symptoms.
AB - Many patients with diabetes have poorly controlled blood sugar levels and remain
at risk for serious diabetes complications, despite access to effective diabetes
treatments and services. Using the transactional model of stress and coping
framework, the study investigated the contributions of affect (Positive and
Negative Affect Schedule) and coping (maladaptive and adaptive coping from the
Brief Cope) on diabetes self-management behaviors, namely diet and exercise. One
hundred seventy-eight rural adults with uncontrolled diabetes and moderate
depressive symptoms completed the measures. Multiple regression analyses
demonstrated that positive affect and negative affect were significantly
associated with diet and exercise, even after adjusting for diabetes severity,
illness intrusiveness, and diabetes knowledge. However, two path analyses
clarified that adaptive coping mediated the relationships between affect
(positive and negative) and self-management behaviors (diet and exercise).
Comprehensive diabetes treatments that include self-management support can assist
patients in recognition and use of adaptive emotion-focused coping skills.
PMID- 29332266
TI - Association Between the Interferon Gamma 874 T/A Polymorphism and the Severity of
Valvular Damage in Patients with Rheumatic Heart Disease.
AB - Interferon gamma (IFN-gamma) is a multifunctional cytokine that plays an
important role in modulating almost all phases of the immune response and may be
responsible for the increased valvular fibrosis and calcification in the
pathogenesis of rheumatic heart disease (RHD). The aim of this study was to
investigate the possible relationship between the IFN-gamma +874 T/A polymorphism
and the severity of valvular damage in the Turkish population. The IFN-gamma
genotypes were determined in 152 RHD patients and 151 healthy controls by ARMS
PCR. Differences in genotype distribution between patients with RHD and control
were evaluated by the chi2 test. All statistical analyses were performed with
SPSS 15.0 Software program. Frequency of the AA genotype was found to be
significantly lower and the TT genotype significantly higher in the RHD group
compared to controls (p = 0.002 and p = 0.018, respectively). The TT genotype was
found to be significantly higher (26.8% vs. 9.1%, p = 0.009) and the AA genotype
significantly lower (29.1% vs. 8.2%, p = 0.001) in the severe valvular disease
(SVD) group compared to mild valvular disease group. In the SVD group, 79
patients had mitral balloon valvotomy and/or mitral valve replacement and had
significantly higher TT genotype compared to patients with medical follow-up
(30.4% vs. 19%, p = 0.001). The data demonstrated that TT genotype is associated
with both RHD and the severity of RHD.
PMID- 29332267
TI - IFN-lambda: A new spotlight in innate immunity against influenza virus infection.
PMID- 29332265
TI - Review of a Parent's Influence on Pediatric Procedural Distress and Recovery.
AB - Understanding how parents influence their child's medical procedures can inform
future work to reduce pediatric procedural distress and improve recovery
outcomes. Following a pediatric injury or illness diagnosis, the associated
medical procedures can be potentially traumatic events that are often painful and
distressing and can lead to the child experiencing long-term physical and
psychological problems. Children under 6 years old are particularly at risk of
illness or injury, yet their pain-related distress during medical procedures is
often difficult to manage because of their young developmental level. Parents can
also experience ongoing psychological distress following a child's injury or
illness diagnosis. The parent and parenting behavior is one of many risk factors
for increased pediatric procedural distress. The impact of parents on pediatric
procedural distress is an important yet not well-understood phenomenon. There is
some evidence to indicate parents influence their child through their own
psychological distress and through parenting behavior. This paper has three
purposes: (1) review current empirical research on parent-related risk factors
for distressing pediatric medical procedures, and longer-term recovery outcomes;
(2) consider and develop existing theories to present a new model for
understanding the parent-child distress relationship during medical procedures;
and (3) review and make recommendations regarding current assessment tools and
developing parenting behavior interventions for reducing pediatric procedural
distress.
PMID- 29332268
TI - Methylmercury Intoxication Promotes Metallothionein Response and Cell Damage in
Salivary Glands of Rats.
AB - Environmental and occupational mercury exposure is considered a major public
health issue. Despite being well known that MeHg exposure causes adverse effects
in several physiologic functions, MeHg effects on salivary glands still not
completely elucidated. Here, we investigated the cellular MeHg-induced damage in
the three major salivary glands (parotid, submandibular, and sublingual) of adult
rats after chronic, systemic and low doses of MeHg exposure. Rats were exposed by
0.04 mg/kg/day over 60 days. After that, animals were euthanized and all three
glands were collected. We evaluated total Hg accumulation, metallothionein I/II
(MT I/II), alpha-smooth muscle actin (alpha-SMA), and cytokeratin 18 (CK18)
immune expression. Our results have showed that MeHg is able to disrupt gland
tissue and to induce a protective mechanism by MT I/II expression. We also showed
that cell MT production is not enough to protect gland tissue against cellular
structural damage seen by reducing marking of cytoskeletal proteins as CK18 and
alpha-SMA. Our data suggest that chronic MeHg exposure in low-daily doses is able
to induce cellular damage in rat salivary glands.
PMID- 29332270
TI - Correction to: Hyper-response to Novelty Increases c-Fos Expression in the
Hippocampus and Prefrontal Cortex in a Rat Model of Schizophrenia.
AB - The original version of this article unfortunately contained a mistake. The
spelling of the author Tommaso Ianniti was incorrect and has been corrected as
Tommaso Iannitti. The original article has been corrected.
PMID- 29332269
TI - Behavioral, Biochemical and Molecular Characterization of a Parkinson's Disease
Mouse Model Using the Neurotoxin 2'-CH3-MPTP: A Novel Approach.
AB - The neurotoxin MPTP has long been used to create a mouse model of Parkinson's
disease (PD). Indeed, several MPTP analogues have been developed, including 2'
CH3-MPTP, which was shown to induce nigrostriatal DA neuronal depletion more
potently than MPTP. However, no study on behavioral and molecular alterations in
response to 2'-CH3-MPTP has been carried out so far. In the present work, 2'-CH3
MPTP was administered to mice (2.5, 5.0 and 10 mg/kg per injection, once a day, 5
days) and histological, biochemical, molecular and behavioral alterations were
evaluated. We show that, despite a dose-dependent-like pattern observed for
nigrostriatal dopaminergic neuronal death and dopamine depletion, dose-specific
alterations in dopamine metabolism and in the expression of dopaminergic
neurotransmission-associated genes could be related to specific motor deficits
elicited by the different doses tested. Interestingly, 2'-CH3-MPTP leads to
increased DAT and MAO-B transcription, which could explain, respectively, its
higher potency and the requirement of higher doses of MAO inhibitors to prevent
nigrostriatal neuronal death when compared to MPTP. Also, perturbations in
dopamine metabolism as well as possible alterations in dopamine bioavailability
in the synaptic cleft were also identified and correlated with strength and
ambulation deficits in response to specific doses. Overall, the present work
brings new evidence supporting the distinct effects of 2'-CH3-MPTP when compared
to its analogue MPTP. Moreover, our data highlight the utmost importance of a
precise experimental design, as different administration regimens and doses yield
different biochemical, molecular and behavioral alterations, which can be
explored to study specific aspects of PD.
PMID- 29332271
TI - Biodegradation of plastics: current scenario and future prospects for
environmental safety.
AB - Plastic is a general term used for a wide range of high molecular weight organic
polymers obtained mostly from the various hydrocarbon and petroleum derivatives.
There is an ever-increasing trend towards the production and consumption of
plastics due to their extensive industrial and domestic applications. However, a
wide spectrum of these polymers is non-biodegradable with few exceptions. The
extensive use of plastics, lack of waste management, and casual community
behavior towards their proper disposal pose a significant threat to the
environment. This has raised growing concerns among various stakeholders to
devise policies and innovative strategies for plastic waste management, use of
biodegradable polymers especially in packaging, and educating people for their
proper disposal. Current polymer degradation strategies rely on chemical,
thermal, photo, and biological procedures. In the presence of proper waste
management strategies coupled with industrially controlled biodegradation
facilities, the use of biodegradable plastics for some applications such as
packaging or health industry is a promising and attractive option for economic,
environmental, and health benefits. This review highlights the classification of
plastics with special emphasis on biodegradable plastics and their rational use,
the identified mechanisms of plastic biodegradation, the microorganisms involved
in biodegradation, and the current insights into the research on biodegradable
plastics. The review has also identified the research gaps in plastic
biodegradation followed by future research directions.
PMID- 29332272
TI - Comparative study of selenium and selenium nanoparticles with reference to acute
toxicity, biochemical attributes, and histopathological response in fish.
AB - Recent studies have demonstrated that selenium (Se) and selenium nanoparticles
(Se-NPs) exhibited toxicity at a higher concentration. The lethal concentration
of Se and Se-NPs was estimated as 5.29 and 3.97 mg/L at 96 h in Pangasius
hypophthalmus. However, the effect of different definite concentration of Se
(4.5, 5.0, 5.5, and 6.0 mg/L) and Se-NPs (2.5, 3.0, 3.5, and 4.0 mg/L) was
decided for acute experiment. Selenium and Se-NPs alter the biochemical
attributes such as anti-oxidative status [catalase (CAT), superoxide dismutase
(SOD), and glutathione-S-transferase (GST) activities], neurotransmitter enzyme,
cellular metabolic enzymes, stress marker, and histopathology of P. hypophthalmus
in a dose- and time-dependent manner. CAT, SOD, and GST were significantly
elevated (p < 0.01) when exposed to Se and Se-NPs, and similarly, a
neurotransmitter enzyme (acetylcholine esterase (AChE)) was significantly
inhibited in a time- and dose-dependent manner. Further, aspartate
aminotransferase, alanine aminotransferase, lactate dehydrogenase, and malate
hydrogenase were noticeably (p < 0.01) affected by Se and Se-NPs from higher
concentration to lower concentration. Stress markers such as cortisol and HSP 70
were drastically enhanced by exposure to Se and Se-NPs. All the cellular
metabolic and stress marker parameters were elevated which might be due to
hyperaccumulation of Se and Se-NPs in the vital organ and target tissues. The
histopathology of liver and gill was also altered such as large vacuole, cloudy
swelling, focal necrosis, interstitial edema, necrosis in liver, and thickening
of primary lamellae epithelium and curling of secondary lamellae due to Se and Se
NP exposure. The study suggested that essential trace element in both forms
(inorganic and nano) at higher concentration in acute exposure of Se and Se-NPs
led to pronounced deleterious alteration on histopathology and cellular and
metabolic activities of P. hypophthalmus.
PMID- 29332273
TI - Pollution and ecological risk assessment of nutrients associated with deposited
sediments collected from roof and road surfaces.
AB - Surface-deposited sediment in urban areas is an essential environmental medium
for assessing nutrient contamination. The total nitrogen (TN) and total
phosphorus (TP) pollution associated with surface-deposited sediments can be
transported into urban water bodies by runoff and can cause eutrophication of
those water bodies. By analyzing the samples collected on roof surfaces and road
surfaces, this study provides a comparison of the differences in TN and TP
pollution loading in sediments on these two different impervious surface
materials. Also, an assessment of the ecological risk of nutrients in surface
deposited sediments with respect to grain size fraction was performed. The
results indicate that the TN and TP pollution loading in both road-deposited
sediments and roof-deposited sediments indicated an asymmetric "W" trend along
with grain size fraction, and both road-deposited sediments and roof-deposited
sediments had the highest TN and TP pollution contribution when the particle size
is between 250 and 500 MUm. TN in roof-deposited sediments has high ecological
risk when the particle size is less than 250 MUm. These findings help to provide
guidance for the management of surface-deposited sediment pollution.
PMID- 29332275
TI - Impact of drought stress induced by polyethylene glycol on growth, water
relations and cell viability of Norway spruce seedlings.
AB - We investigated physiological responses of 7-week-old Norway spruce seedlings to
water deficits of different intensities. Hydroponically grown seedlings were
subjected to mild (-0.15 MPa), strong (-0.5 and -1.0 MPa) and extreme (-1.5 MPa)
water deficit induced by polyethylene glycol 6000, and their growth parameters,
water status and physiological activity were analyzed. Seedlings effectively
restricted water loss under drought, and even under extreme water deficit, shoot
relative water content did not fall below 85%. Water stress induced substantial
decreases in the osmotic potentials of root and needle cell sap, up to 0.3-0.4
MPa under extreme water deficit, though this did not result from water loss or
accumulation of K+ and Na+ ions. Seedling growth was very susceptible to water
stress because of poor capacity for cell wall adjustment. Water stress injured
seedling roots, as evidenced by the loss of root cell physiological activity
estimated by the ability to hydrolyse fluorescein diacetate and by increased root
calcium content up to 8-10-fold under extreme water stress. At the same time,
root hair growth was enhanced, especially under mild water deficit, which
increased the root water-absorbing capacity. In summary, seedlings of Norway
spruce were characterized by high susceptibility to water stress and concurrently
by pronounced ability to maintain water status. These characteristics are fully
consistent with spruce confinement to moist habitats.
PMID- 29332274
TI - Callitriche cophocarpa (water starwort) proteome under chromate stress: evidence
for induction of a quinone reductase.
AB - Chromate-induced physiological stress in a water-submerged macrophyte Callitriche
cophocarpa Sendtn. (water starwort) was tested at the proteomic level. The
oxidative stress status of the plant treated with 1 mM Cr(VI) for 3 days revealed
stimulation of peroxidases whereas catalase and superoxide dismutase activities
were similar to the control levels. Employing two-dimensional electrophoresis,
comparative proteomics enabled to detect five differentiating proteins subjected
to identification with mass spectrometry followed by an NCBI database search.
Cr(VI) incubation led to induction of light harvesting chlorophyll a/b binding
protein with a concomitant decrease of accumulation of ribulose bisphosphate
carboxylase (RuBisCO). The main finding was, however, the identification of an
NAD(P)H-dependent dehydrogenase FQR1, detectable only in Cr(VI)-treated plants.
The FQR1 flavoenzyme is known to be responsive to oxidative stress and to act as
a detoxification protein by protecting the cells against oxidative damage. It
exhibits the in vitro quinone reductase activity and is capable of catalyzing two
electron transfer from NAD(P)H to several substrates, presumably including
Cr(VI). The enhanced accumulation of FQR1 was chromate-specific since other
stressful conditions, such as salt, temperature, and oxidative stresses, all
failed to induce the protein. Zymographic analysis of chromate-treated
Callitriche shoots showed a novel enzymatic protein band whose activity was
attributed to the newly identified enzyme. We suggest that Cr(VI)
phytoremediation with C. cophocarpa can be promoted by chromate reductase
activity produced by the induced quinone oxidoreductase which might take part in
Cr(VI) -> Cr(III) bioreduction process and thus enable the plant to cope with the
chromate-generated oxidative stress.
PMID- 29332276
TI - Variability and reliability of POP concentrations in multiple breast milk samples
collected from the same mothers.
AB - Risk assessment of infant using a realistic persistent organic pollutant (POP)
exposure through breast milk is essential to devise future regulation of POPs.
However, recent investigations have demonstrated that POP levels in breast milk
collected from the same mother showed a wide range of variation daily and
monthly. To estimate the appropriate sample size of breast milk from the same
mother to obtain reliable POP concentrations, breast milk samples were collected
from five mothers living in Japan from 2006 to 2012. Milk samples from each
mother were collected 3 to 6 times a day through 3 to 7 days consecutively. Food
samples as the duplicated method were collected from two mothers during the
period of breast milk sample collection. Those were employed for POP (PCBs, DDTs,
chlordanes, and HCB) analysis. PCB concentrations detected in breast milk samples
showed a wide range of variation which was maximum 63 and 60% of relative
standard deviation (RSD) in lipid and wet weight basis, respectively. The time
course trend of those variations among the mothers did not show any typical
pattern. A larger amount of PCB intake through food seemed to affect 10 h after
those concentrations in breast milk in lipid weight basis. Intraclass correlation
coefficient (ICC) analyses indicated that the appropriate sample size for good
reproducibility of POP concentrations in breast milk required at least two
samples for lipid and wet weight basis.
PMID- 29332277
TI - Efficient degradation of triclosan by an endophytic fungus Penicillium oxalicum
B4.
AB - Triclosan (TCS), a widely used antimicrobial and preservative agent, is an
emerging contaminant in aqueous and soil environment. Microbial degradation of
TCS has not been reported frequently because of its inhibition of microbe growth.
To explore the new microbial resources for TCS biodegradation, fungal endophytes
were isolated and screened for the degradation potential. The endophytic strain
B4 isolated from Artemisia annua L. showed higher degradation efficiency and was
identified as Penicillium oxalicum based on its morphology and ITS sequences of
ribosomal DNA. In both medium and synthetic wastewater, TCS (5 mg/L) was almost
completely degraded within 2 h by the strain B4. The high capacity of TCS uptake
(127.60 +/- 8.57 mg/g dry weight, DW) of fungal mycelium was observed during the
first 10 min after TCS addition. B4 rapidly reduced initial content (5.00 mg/L)
of TCS to 0.41 mg/L in medium in 10 min. Then, the accumulation of TCS in
mycelium was degraded from 0.45 to 0.05 mg/g DW after 1-h treatment. The
degradation metabolites including 2-chlorohydroquinone, 2, 4-dichloropheno, and
hydroquinone were found to be restrained in mycelia. The end products of the
biodegradation in medium showed no toxicity to Escherichia coli. The new
characteristics of high adsorption, fast degradation, and low residual toxicity
highlight the potential of endophytic P. oxalicum B4 in TCS bioremediation.
PMID- 29332278
TI - Exposure to nanoscale and microscale particulate air pollution prior to mining
development near a northern indigenous community in Quebec, Canada.
AB - This study serves as a baseline characterization of indoor and outdoor air
quality in a remote northern indigenous community prior to the start of a major
nearby mining operation, including measurements of nanoparticles, which has never
been performed in this context before. We performed aerosol sample collection and
real-time aerosol measurements at six different locations at the Cree First
Nation of Waswanipi and the Montviel campsite, located 45 km west of the Cree
First Nation of Waswanipi, in the south of the Nord-du-Quebec region. High
concentrations of airborne nanoparticles (up to 3.98 * 104 +/- 8.9 * 103 cm-3 at
64.9-nm midpoint particle diameter) and fine particles (up to 1.99 * 103 +/- 1.6
* 102 cm-3 at 0.3-MUm midpoint particle diameter) were measured inside a
residential home, where we did not find any ventilation or air filtration
systems. The most abundant particle sizes by mass were between 0.19 and 0.55 MUm.
The maximum concentration of analyzed heavy metals was detected at the d50 cut
off particle size of 0.31 MUm; and the most abundant heavy metals in the aerosol
samples were Al, Ba, Zn, Cu, Hg, and Pb. We concluded that the sources of the
relatively high indoor particle concentrations were likely laundry machines and
cooking emissions in the absence of a sufficient ventilation system. However, the
chemical composition of particles resulting from mining activities is expected to
be different from that of the aerosol particles from indoor sources. Installation
and proper maintenance of sufficient ventilation and air filtration systems may
reduce the total burden of disease from outdoor and indoor air pollution and
remediate infiltrated indoor particulate pollution from the mining sources as
well.
PMID- 29332279
TI - Ecotoxicity thresholds for ametryn, diuron, hexazinone and simazine in fresh and
marine waters.
AB - Triazine and urea herbicides are two groups of photosystem II inhibiting
herbicides frequently detected in surface, ground and marine waters. Yet, there
are few water quality guidelines for herbicides. Ecotoxicity thresholds (ETs) for
ametryn, hexazinone and simazine (triazine herbicides) and diuron (a urea
herbicide) were calculated using the Australian and New Zealand method for
deriving guideline values to protect fresh and marine ecosystems. Four ETs were
derived for each chemical and ecosystem that should theoretically protect 99, 95,
90 and 80% of species (i.e. PC99, PC95, PC90 and PC80, respectively). For all
four herbicides, the phototrophic species were significantly more sensitive than
non-phototrophic species, and therefore, only the former data were used to
calculate the ETs. Comparison of the ET values to measured concentrations in 2606
samples from 15 waterways that discharge to the Great Barrier Reef (2011-2015)
found three exceedances of the simazine PC99, regular exceedances (up to 30%) of
the PC99 in a limited number of rivers for ametryn and hexazinone and frequent (>
40%) exceedances of the PC99 and PC95 ETs in at least four waterways for diuron.
There were no exceedances of the marine ETs in inshore reef areas. Further,
ecotoxicity data are required for ametryn and hexazinone to fresh and marine
phototrophic species, for simazine to marine phototrophic species, for tropical
phototrophic species, repeated pulse exposures and long-term (2 to 12 months)
exposures to environmentally relevant concentrations.
PMID- 29332280
TI - Hydrogeochemical processes and influence of seawater intrusion in coastal
aquifers south of Chennai, Tamil Nadu, India.
AB - Seawater intrusion promotes the salinity of groundwater, and it poses a great
environmental impact on a global scale. The present study was carried out to
determine the hydrogeochemical processes and influence of seawater intrusion in
the coastal aquifers using geophysical, geochemical, and stable isotope
techniques. The true resistivity value ranges from 0.5 to 8008.5 Omega-m which
has been measured using vertical electrical sounding (VES) based on the
Schlumberger method. About 33 groundwater samples were collected during post
monsoon (POM) (January 2012) and pre-monsoon (PRM) (June 2012) seasons from open
and bore wells and were analyzed for major ions and stable isotopes. EC, Na+, and
Cl- were high in groundwater of wells near salt pan, the Buckingham Canal, and
backwater regions. Around 45% of the groundwater of this study area is of Na+-Cl-
type due to salinisation. Reverse ion exchange and silicate weathering are the
dominant processes controlling the geochemistry of groundwater. Saturation
indexes (SI) of halite (SIhalite) and gypsum (SIgypsum) versus sulfate show an
increasing trend line from > 0 to < 0, which implies higher dissolution of
minerals and hints increasing salinization during both seasons. The value of
Na+/Cl- ranges between 0.7 and 2.4 (POM) and from 0.6 to 2.8 (PRM). The molar
ratio suggested that around 25% of the groundwater samples are with values
similar to those of seawater. Further, the groundwater is also affected by saline
backwater, salt pan activities, and Buckingham Canal. Some locations are also are
affected by anthropogenic, agricultural activities and geochemical processes.
Heavy stable isotopes were found to be dominant in the coastal region due to
seawater intrusion. Stable isotopes of delta18O range from - 5.6 to - 2.90/00
during both periods. About 201 km2 of this area is affected by salinization. It
is necessary to reduce pumping and plan for physical barriers to create
freshwater ridges for controling the seawater intrusion.
PMID- 29332281
TI - Programmed Cell Death in Plants: An Overview.
AB - Programmed cell death (PCD) is a controlled mechanism that eliminates specific
cells under developmental or environmental stimuli. All organisms-from bacteria
to multicellular eukaryotes-have the ability to induce PCD in selected cells.
Although this process was first identified in plants, the interest in deciphering
the signaling pathways leading to PCD strongly increased when evidence came to
light that PCD may be involved in several human diseases. In plants, PCD
activation ensures the correct occurrence of growth and developmental processes,
among which embryogenesis and differentiation of tracheary elements. PCD is also
part of the defense responses activated by plants against environmental stresses,
both abiotic and biotic.This chapter gives an overview of the roles of PCD in
plants as well as the problems arising in classifying different kinds of PCD
according to defined biochemical and cellular markers, and in comparison with the
various types of PCD occurring in mammal cells. The importance of understanding
PCD signaling pathways, with their elicitors and effectors, in order to improve
plant productivity and resistance to environmental stresses is also taken into
consideration.
PMID- 29332282
TI - Investigation of Morphological Features of Autophagy During Plant Programmed Cell
Death.
AB - The investigation of autophagy particularly when observed during programmed cell
death (PCD) is strongly based on the morphological features recorded with
transmission electron microscope (TEM). Here we describe methods to induce and to
inhibit autophagy in plants. Also some tips for obtaining better preservation of
biological membranes, crucial for the investigation of autophagy, are provided
together with information about plant autophagic mutants, use of antibodies and
methods for 3D reconstruction of large membrane-bound objects that are commonly
formed during autophagic processes leading to PCD in plants.
PMID- 29332283
TI - Markers of Developmentally Regulated Programmed Cell Death and Their Analysis in
Cereal Seeds.
AB - Programmed cell death (PCD) is a key process for the development and
differentiation of multicellular organisms, which is characterized by well
defined morphological and biochemical features. These include chromatin
condensation, DNA degradation and nuclear fragmentation, with nucleases and
proteases playing a relevant function in these processes. In this chapter we
describe methods routinely used for the analysis of hallmarks of developmentally
regulated PCD in cereal seed tissues, which are based on agarose and
polyacrylamide gel electrophoresis, in situ staining of DNA fragmentation, and
cell-free assays of relevant enzymatic activities.
PMID- 29332284
TI - Measurement of Hypersensitive Cell Death Triggered by Avirulent Bacterial
Pathogens in Arabidopsis.
AB - The hypersensitive response is one of the most powerful and complex defense
reactions to survive to pathogen attacks during an incompatible plant-pathogen
interaction. Local programmed cell death accompanies the hypersensitive response
at the site of infection to prevent pathogen growth and spread. A precise
quantitative assessment of this form of programmed cell death is essential to
unravel the genetic and molecular mechanisms underlying the process. Here, we
first describe the optimization of a Trypan Blue staining protocol for
quantitatively measuring the HR-cell death in Arabidopsis. Furthermore, we
provide an electrolyte leakage protocol based on pathogen vacuum infiltration,
which allows its simultaneous application to a large number of plants as well as
to Arabidopsis mutants affected by small size phenotype.
PMID- 29332285
TI - Immunity-Associated Programmed Cell Death as a Tool for the Identification of
Genes Essential for Plant Innate Immunity.
AB - Plants have evolved a sophisticated innate immune system to contend with
potential infection by various pathogens. Understanding and manipulation of key
molecular mechanisms that plants use to defend against various pathogens are
critical for developing novel strategies in plant disease control. In plants,
resistance to attempted pathogen infection is often associated with
hypersensitive response (HR), a form of rapid programmed cell death (PCD) at the
site of attempted pathogen invasion. In this chapter, we describe a method for
rapid identification of genes that are essential for plant innate immunity. It
combines virus-induced gene silencing (VIGS), a tool that is suitable for
studying gene function in high-throughput, with the utilization of immunity
associated PCD, particularly HR-linked PCD as the readout of changes in plant
innate immunity. The chapter covers from the design of gene fragment for VIGS,
the agroinfiltration of the Nicotiana benthamian plants, to the use of immunity
associated PCD induced by twelve elicitors as the indicator of activation of
plant immunity.
PMID- 29332286
TI - Analysis of Mitochondrial Markers of Programmed Cell Death.
AB - Mitochondria play a crucial role in programmed cell death (PCD) in plants. In
most cases of mitochondria-dependent PCD, cytochrome c (Cyt c) released from
mitochondria due to the opening of mitochondrial permeability transition pore
(MPTP) and the activation of caspase-like proteases. Here we describe the
analytic methods of mitochondrial markers of PCD including mitochondria
isolation, mitochondrial membrane permeability, mitochondrial inner membrane
potential, Cytc release, ATP, and mitochondrial reactive oxygen species (ROS).
PMID- 29332287
TI - Studying Retrograde Signaling in Plants.
AB - Cellular homeostasis requires precise communication between various types of
organelles. In particular, the communication between nucleus and semiautonomous
organelles, mitochondria and chloroplasts, has received widespread attention.
Communication from nucleus to other organelles is known as anterograde signaling,
whereas communication from mitochondria or chloroplasts to the nucleus is known
as retrograde signaling. Here we discuss methods used to study retrograde
signaling in Arabidopsis thaliana. These methods may also be modified to study
retrograde signaling in other plant species.
PMID- 29332288
TI - ROS and Cell Death in Tomato Roots Infected by Meloidogyne Incognita.
AB - Phytoparasitic nematodes are plant pests causing serious problems to a broad
range of hosts, and Meloidogyne species are widely recognized as the most
damaging among the root knot nematode groups. During the incompatible interaction
between avirulent pathogens and resistant tomato cultivars, juvenile nematode
invasions provoke a defense cascade, culminating in hypersensitive responses.
Methods to detect the key molecules involved in oxidative metabolism of the
infected tomato roots are described here.
PMID- 29332289
TI - Detection of Reactive Oxygen and Nitrogen Species (ROS/RNS) During Hypersensitive
Cell Death.
AB - Reactive oxygen and nitrogen species (ROS/RNS) are signaling molecules involved
in a plethora of physiological processes in plants. Especially, ROS and nitric
oxide (NO) are key players that are required for programmed cell death (PCD). The
PCD associated with the hypersensitive response (HR) has been well characterized
and the role of H2O2 and NO as key signaling molecules inducing HR has been
established. Localization of ROS and NO production in plant tissues in response
to pathogens can be imaged by confocal laser microscopy by using specific
fluorescent probes. Deciphering the time and spatial regulation of ROS and NO is
very important to establish the cellular response of plants to adverse
conditions. This chapter is mainly focused on the imaging of ROS and RNS
accumulation in vivo in plant tissues undergoing PCD.
PMID- 29332291
TI - Analysis of Reactive Carbonyl Species Generated Under Oxidative Stress.
AB - Oxidation of membrane lipids by reactive oxygen species primarily generates lipid
peroxides, from which various carbonyls, i.e., aldehydes and ketones, are formed.
Among them, those with a carbonyl-conjugated C-C double bond have significant
biological functions and are designated as reactive carbonyl species (RCS). A
dozen kinds of RCS occurring in plant cells have a broad spectrum of reactivity
and biological effects, depending on the structure. Several RCS have been
recently found to activate caspase-like proteases in plants, thereby initiating
PCD. Comprehensive and quantitative RCS analysis method using conventional HPLC
is illustrated.
PMID- 29332290
TI - DNA Diffusion Assay Applied to Plant Cells.
AB - DNA diffusion assay is a simple, sensitive and reliable technique which allows
the assessment of programmed cell death (PCD) or necrosis events based on nuclear
morphology. It consists in isolating nuclei from plant material, which are then
embedded in agarose and subjected to lysis in alkaline buffers. Under these
conditions, and due to the presence of abundant alkali-labile sites in the DNA,
small pieces of DNA diffuse in the agarose gel giving a specific halo appearance
when stained with fluorescent dyes like DAPI (4',6-diamidino-2-phenylindole).
Here, we describe an optimized protocol for DNA diffusion assay applied to
different types of plant cells/tissues, indicating all the critical steps
required for a successful experimental procedure.
PMID- 29332292
TI - In Vivo Analysis of Calcium Levels and Glutathione Redox Status in Arabidopsis
Epidermal Leaf Cells Infected with the Hypersensitive Response-Inducing Bacteria
Pseudomonas syringae pv. tomato AvrB (PstAvrB).
AB - Plants react to the attack of pathogen microorganisms by mounting appropriate and
efficient downstream defense responses often involving a form of localized cell
death called hypersensitive response (HR).Here we describe an innovative and
noninvasive protocol based on in vivo bioimaging technique coupled with
utilization of genetically encoded fluorescent sensors that allows to monitor and
analyze intracellular calcium (Ca2+) dynamics and changes of the glutathione
redox status taking place in plant organs during plant interaction with the HR
inducing bacteria Pseudomonas syringae (PstAvrB).
PMID- 29332293
TI - Measurement of Cyclic GMP During Plant Hypersensitive Disease Resistance
Response.
AB - Cyclic guanosine-3',5'-monophosphate (cGMP) is recognized as an important second
messenger in plants, mediating intracellular signal in important physiological
processes, including the hypersensitive disease resistance response induced by
avirulent pathogens. In this context, the analysis of cGMP levels in infected
plants requires an accurate and specific detection method allowing its
quantification. Here, we describe an assay based on the Alphascreen technology,
developed for animal cells and further adapted and optimized for the detection of
cGMP in plants. The method is applied for the measurement of cGMP in Arabidopsis
thaliana plants challenged with an avirulent strain of Pseudomonas syringae pv.
tomato. This protocol includes the extraction of cGMP, the assay procedure and
the calculation of cGMP concentration.
PMID- 29332294
TI - Detection of MAPK3/6 Phosphorylation During Hypersensitive Response (HR)
Associated Programmed Cell Death in Plants.
AB - Programmed cell death (PCD) is an essential component of development, biotic and
abiotic responses. Hypersensitive response (HR)-associated cell death activated
under pathogen attack is one of the most dramatic manifestations of PCD in
plants. Signal transduction through mitogen-activated protein kinase (MAPK)
cascades, a very conserved signaling pathway across eukaryotes, is a core
mediator for HR-associated PCD. Therefore, monitoring MAPK activation enables the
mechanisms underlying HR-associated PCD to be elucidated. Here, we describe the
use of a phosphorylation-specific MAPK3/6 antibody to monitor the activation of
MAPK3/6 during HR-associated PCD. The technique may be adapted for use in other
types of PCD.
PMID- 29332295
TI - Measurement of the Caspase-1-Like Activity of Vacuolar Processing Enzyme in
Plants.
AB - Caspase-like activities are essential to regulate programed cell death in plants.
Although no caspase orthologous enzymes with aspartic acid specificity have been
identified in plants, vacuolar processing enzyme (VPE) exhibits a caspase-1-like
activity. In this chapter, we introduce two methods for the measurement of the
caspase-1-like/VPE activity. These methods are based on the cleavage of caspase-1
specific synthetic substrates and on monitoring the active forms of VPE using a
biotinylated-inhibitor blot analysis. Both methods are also adaptable to other
plant caspase-like activities.
PMID- 29332296
TI - Plant Cell Cultures as Model Systems to Study Programmed Cell Death.
AB - The study of programmed cell death (PCD) activated in a certain group of cells is
complex when analyzed in the whole plant. Plant cell suspension cultures are
useful when investigating PCD triggered by environmental and developmental
stimuli. Due to their homogeneity and the possibility to synchronize their
responses induced by external stimuli, these cultures are used for studying the
signaling pathways leading to PCD. The first problem in the analysis of PCD in
cell cultures is the quantification of cell viability/death over time. Cultured
cells from different plant species may have specific mitotic patterns leading to
calli or cell chains mixed to single cell suspensions. For this reason, not all
cell cultures allow morphological parameters to be investigated using microscopy
analysis, and adapted or ad hoc methods are needed to test cell viability.Here we
report on some accurate methods to establish and propagate cell cultures from
different plant species, including crops, as well as to determine cell viability
and PCD morphological and genetic markers. In particular, we describe a protocol
for extracting nucleic acids required for real-time PCR analysis which has been
optimized for those cell cultures that do not allow the use of commercial kits.
PMID- 29332297
TI - Integrodifference equations in the presence of climate change: persistence
criterion, travelling waves and inside dynamics.
AB - To understand the effects that the climate change has on the evolution of species
as well as the genetic consequences, we analyze an integrodifference equation
(IDE) models for a reproducing and dispersing population in a spatio-temporal
heterogeneous environment described by a shifting climate envelope. Our analysis
on the IDE focuses on the persistence criterion, travelling wave solutions, and
the inside dynamics. First, the persistence criterion, characterizing the global
dynamics of the IDE, is established in terms of the basic reproduction number. In
the case of persistence, a unique travelling wave is found to govern the global
dynamics. The effects of the size and the shifting speed of the climate envelope
on the basic reproduction number, and hence, on the persistence criterion, are
also investigated. In particular, the critical domain size and the critical
shifting speed are found in certain cases. Numerical simulations are performed to
complement the theoretical results. In the case of persistence, we separate the
travelling wave and general solutions into spatially distinct neutral fractions
to study the inside dynamics. It is shown that each neutral genetic fraction
rearranges itself spatially so as to asymptotically achieve the profile of the
travelling wave. To measure the genetic diversity of the population density we
calculate the Shannon diversity index and related indices, and use these to
illustrate how diversity changes with underlying parameters.
PMID- 29332298
TI - The ESS and replicator equation in matrix games under time constraints.
AB - Recently, we introduced the class of matrix games under time constraints and
characterized the concept of (monomorphic) evolutionarily stable strategy (ESS)
in them. We are now interested in how the ESS is related to the existence and
stability of equilibria for polymorphic populations. We point out that, although
the ESS may no longer be a polymorphic equilibrium, there is a connection between
them. Specifically, the polymorphic state at which the average strategy of the
active individuals in the population is equal to the ESS is an equilibrium of the
polymorphic model. Moreover, in the case when there are only two pure strategies,
a polymorphic equilibrium is locally asymptotically stable under the replicator
equation for the pure-strategy polymorphic model if and only if it corresponds to
an ESS. Finally, we prove that a strict Nash equilibrium is a pure-strategy ESS
that is a locally asymptotically stable equilibrium of the replicator equation in
n-strategy time-constrained matrix games.
PMID- 29332299
TI - Similarity search combined with docking and molecular dynamics for novel hAChE
inhibitor scaffolds.
AB - The main purpose of this study was to address the performance of virtual
screening methods based on ligands and the protein structure of
acetylcholinesterase (AChE) in order to retrieve novel human AChE (hAChE)
inhibitors. In addition, a protocol was developed to identify novel hit compounds
and propose new promising AChE inhibitors from the ZINC database with 10 million
commercially available compounds. In this sense, 3D similarity searches using
rapid overlay of chemical structures and similarity analysis through comparison
of electrostatic overlay of docked hits were used to retrieve AChE inhibitors
from collected databases. Molecular dynamics simulation of 100 ns was carried out
to study the best docked compounds from similarity searches. Some key residues
were identified as crucial for the dual binding mode of inhibitor with the
interaction site. All results indicated the relevant use of EON and docking
strategy for identifying novel hit compounds as promising potential
anticholinesterase candidates, and seven new structures were selected as
potential hAChE inhibitors. Graphical abstract Compound N01 in the 4M0E hAChE
crystallography structure from docking results. Yellow dashed lines Hydrogen
bonds, blue dashed lines pi-stacking interactions, green dashed lines cation-pi
interactions.
PMID- 29332300
TI - Long term exposure to cell phone frequencies (900 and 1800 MHz) induces
apoptosis, mitochondrial oxidative stress and TRPV1 channel activation in the
hippocampus and dorsal root ganglion of rats.
AB - Mobile phone providers use electromagnetic radiation (EMR) with frequencies
ranging from 900 to 1800 MHz. The increasing use of mobile phones has been
accompanied by several potentially pathological consequences, such as
neurological diseases related to hippocampal (HIPPON) and dorsal root ganglion
neuron (DRGN). The TRPV1 channel is activated different stimuli, including CapN,
high temperature and oxidative stress. We investigated the contribution TRPV1 to
mitochondrial oxidative stress and apoptosis in HIPPON and DRGN following long
term exposure to 900 and 1800 MHz in a rat model. Twenty-four adult rats were
equally divided into the following groups: (1) control, (2) 900 MHz, and (3) 1800
MHz exposure. Each experimental group was exposed to EMR for 60 min/ 5 days of
the week during the one year. The 900 and 1800 MHz EMR exposure induced increases
in TRPV1 currents, intracellular free calcium influx (Ca2+), reactive oxygen
species (ROS) production, mitochondrial membrane depolarization (JC-1),
apoptosis, and caspase 3 and 9 activities in the HIPPON and DRGN. These
deleterious processes were further increased in the 1800 MHz experimental group
compared to the 900 MHz exposure group. In conclusion, mitochondrial oxidative
stress, programmed cell death and Ca2+ entry pathway through TRPV1 activation in
the HIPPON and DRGN of rats were increased in the rat model following exposure to
900 and 1800 MHz cell frequencies. Our results suggest that exposure to 900 and
1800 MHz EMR may induce a dose-associated, TRPV1-mediated stress response.
PMID- 29332301
TI - Evaluating Risk Tolerance from a Systematic Review of Preferences: The Case of
Patients with Psoriasis.
AB - BACKGROUND: Stated-preference methods have been widely used to evaluate patient
relative preferences for the benefits and potential harms of psoriasis
treatments. However, risk tolerance measures for treatment-related harms, a
corollary of preferences, are rare despite their critical role in shared decision
making and regulatory benefit-risk evaluations. This article presents a method to
enhance information on patient risk tolerance through previously published
preference results. OBJECTIVE: The objective of this article was to conduct the
first meta-analysis of preferences to characterize the distribution of patients'
maximum acceptable risk of harms associated with psoriasis treatments. DATA
SOURCES: Maximum acceptable risks for treatment-related adverse events were
extracted or derived from preference results published between 2011 and 2017.
SYNTHESIS METHODS: Four different analyses were conducted to evaluate maximum
acceptable risk information across studies: (1) listing of maximum acceptable
risk values, (2) naive aggregation of maximum acceptable risks, (3) estimation of
maximum acceptable risk mother distribution, and (4) random-effect regression
analysis of maximum acceptable risks. RESULTS: Nine publications with maximum
acceptable risk results, or with enough information to derive maximum acceptable
risks, were identified from the search and screening of preference studies. The
most commonly evaluated treatment benefits were duration of benefits, percentage
and probability of improvement, and reductions in the coverage of lesions. The
adverse-event risks most often included in the publications were those commonly
associated with biologics, such as serious infections and malignancies. As
expected, maximum acceptable risks changed with treatment benefits and treatment
related adverse events. CONCLUSIONS: The results confirm the feasibility of using
previously published preference information to characterize patient risk
tolerance. The estimated distributions of maximum acceptable risk provide a
benchmark against which future results can be compared, and signal gaps in our
understanding of risk tolerance for specific health outcomes.
PMID- 29332302
TI - Preoperative Cognitive Impairment As a Predictor of Postoperative Outcomes in a
Collaborative Care Model.
AB - OBJECTIVES: To compare postoperative outcomes of individuals with and without
cognitive impairment enrolled in the Perioperative Optimization of Senior Health
(POSH) program at Duke University, a comanagement model involving surgery,
anesthesia, and geriatrics. DESIGN: Retrospective analysis of individuals
enrolled in a quality improvement program. SETTING: Tertiary academic center.
PARTICIPANTS: Older adults undergoing surgery and referred to POSH (N = 157).
MEASUREMENTS: Cognitive impairment was defined as a score less than 25 out of 30
(adjusted for education) on the St. Louis University Mental Status (SLUMS)
Examination. Median length of stay (LOS), mean number of postoperative
complications, rates of postoperative delirium (POD, %), 30-day readmissions (%),
and discharge to home (%) were compared using bivariate analysis. RESULTS:
Seventy percent of participants met criteria for cognitive impairment (mean SLUMS
score 20.3 for those with cognitive impairment and 27.7 for those without).
Participants with and without cognitive impairment did not significantly differ
in demographic characteristics, number of medications (including anticholinergics
and benzodiazepines), or burden of comorbidities. Participants with and without
cognitive impairment had similar LOS (P = .99), cumulative number of
complications (P = .70), and 30-day readmission (P = .20). POD was more common in
those with cognitive impairment (31% vs 24%), but the difference was not
significant (P = .34). Participants without cognitive impairment had higher rates
of discharge to home (80.4% vs 65.1%, P = .05). CONCLUSION: Older adults with and
without cognitive impairment referred to the POSH program fared similarly on most
postoperative outcomes. Individuals with cognitive impairment may benefit from
perioperative geriatric comanagement. Questions remain regarding the validity of
available measures of cognition in the preoperative period.
PMID- 29332304
TI - The i3S initiative: a Portuguese blend of Research and Innovation.
PMID- 29332303
TI - Mitochondrial DNA, nuclear context, and the risk for carcinogenesis.
AB - The inheritance of mitochondrial DNA (mtDNA) from mother to child is complicated
by differences in the stability of the mitochondrial genome. Although the germ
line mtDNA is protected through the minimization of replication between
generations, sequence variation can occur either through mutation or due to
changes in the ratio between distinct genomes that are present in the mother
(known as heteroplasmy). Thus, the unpredictability in transgenerational
inheritance of mtDNA may cause the emergence of pathogenic mitochondrial and
cellular phenotypes in offspring. Studies of the role of mitochondrial metabolism
in cancer have a long and rich history, but recent evidence strongly suggests
that changes in mitochondrial genotype and phenotype play a significant role in
the initiation, progression and treatment of cancer. At the intersection of these
two fields lies the potential for emerging mtDNA mutations to drive
carcinogenesis in the offspring. In this review, we suggest that this facet of
transgenerational carcinogenesis remains underexplored and is a potentially
important contributor to cancer. Environ. Mol. Mutagen., 2018. (c) 2018 Wiley
Periodicals, Inc.
PMID- 29332305
TI - Oblique thyroarytenoid muscle in humans: An independent muscle or an accessory
belly?
AB - OBJECTIVES/HYPOTHESIS: This study aimed to determine the prevalence and
morphological variations of the oblique thyroarytenoid (TA) muscle in humans.
STUDY DESIGN: Cadaveric anatomic dissections. METHODS: One hundred hemilarynges
from 50 formalin-embalmed cadavers were dissected to investigate the morphology
of muscle fibers of the TA muscle. RESULTS: Thirty-six (36%) hemilarynges were
found to have a distinct oblique belly superficial to the TA muscle. In 28 cases,
the belly had a relatively constant origin and an insertion that extended
straight onto the TA muscle from the anterosuperior area of the internal surface
of the thyroid lamina to the base of the muscular process of the arytenoid
cartilage. Eight cases were located in a similar area but with some differences
in the origin or insertion features. CONCLUSIONS: We proposed that the oblique TA
muscle has a high prevalence and probably acts to close and relax the vocal
cords. It remains to be determined whether the oblique TA muscle is an
independent muscle or an accessory belly of the main TA muscle. LEVEL OF
EVIDENCE: NA. Laryngoscope, 128:1634-1638, 2018.
PMID- 29332306
TI - Current work environments: What problems are being faced by Japanese urologists?
AB - Computer technology has contributed to innovative progress in industrial
infrastructures and has had a major influence on various work environments.
Evaluations of work environments are routinely carried out in Western countries,
but historically there has been resistance to such evaluations in Japan. In this
mini-review, we discuss the current work environments of urologists in Japan. The
number of urologists has increased each year, and the population density of
urologists was 5.4 (per 100 000 people) in 2014. The average age of urologists in
Japan was 48.9 years, and the percentage of female urologists was just 5.3%.
Additionally, the geographic distribution of urologists was uneven in Japan. From
projections based on population dynamics, the need for more urologists in the
near future will probably increase. Because medical environments vary depending
on the country, it is necessary to understand current work environments in
greater detail initially. Furthermore, we should determine original measures for
the establishment of satisfactory urological work environments in Japan.
PMID- 29332307
TI - Scaffold thrombosis following implantation of the ABSORB BVS in routine clinical
practice: Insight into possible mechanisms from optical coherence tomography.
AB - OBJECTIVES: To identify potential underlying mechanisms of early and (very) late
scaffold thrombosis (ScT) by optical coherence tomography (OCT), in a frame-by
frame analysis. BACKGROUND: The absorb scaffold is associated with an increased
risk of ScT compared with metallic stents. Several potential causes of
bioresorbable ScT have been identified, however the precise etiology still
remains unclear. METHODS: Between February 2013 and February 2016, 13 patients
presenting with definite ScT underwent OCT imaging. After guidewire passage or
balloon inflations, OCT images were acquired. Pullbacks were assessed offline at
each 1 mm longitudinal interval within the treated segment and the 5 mm segments
adjacent to both edges. Primary cause of ScT was assessed by reviewing medical
records, baseline angiographic films, and OCT pullback and angiographic films at
time of ScT. RESULTS: 13 patients, with 14 thrombotic lesions presented either
with early ScT (i.e., <=30 days) or very (late) (i.e., >30 days). Analysis
demonstrated a significantly smaller in-scaffold maximal lumen diameter in the
early cases (2.75 +/- 0.85 mm vs. 3.00 +/- 0.46 mm; P = 0.033) and a
nonsignificant smaller minimal scaffold diameter (2.44 +/- 0.62 mm vs. 2.58 +/-
0.37 mm P = 0.097). Per-strut analysis demonstrated significantly more malapposed
scaffold struts in (very) late cases (6% versus 0.6%, P < 0.001). Assessment of
the predominate cause showed underexpansion as the dominant factor in the early
cases, while malapposition was predominantly seen in the (very)late cases.
CONCLUSIONS: OCT performed in patients presenting with Absorb ScT demonstrated
that malapposition of scaffold struts was more prominent in patients presenting
with (very) late ScT, while underexpansion was more frequent in the early cases.
PMID- 29332308
TI - Transcatheter closure of patent foramen ovale for secondary prevention of
ischemic stroke: Quantitative synthesis of pooled randomized trial data.
AB - OBJECTIVES: To evaluate the safety and efficacy of percutaneous device closure of
patent foramen ovale (PFO) for secondary prevention of ischemic stroke
BACKGROUND: Stroke remains the leading cause of serious long-term disability in
the United States. The effectiveness of a percutaneous PFO closure in the
prevention of recurrent cryptogenic strokes has not been established. METHODS: We
performed a literature search using PubMed, EMBASE, Cochrane Central Register of
Controlled Trials, Google Scholar, and Internet-based sources from January 2003
to September 2017. Randomized controlled trails (RCTs) comparing percutaneous PFO
closure to medical therapy alone. RESULTS: Five RCTs (CLOSURE I, PC Trial,
REDUCE, RESPECT, and CLOSE) with 1,829 patients in the device group and 1,611
patients in the medical group met inclusion criteria. The cumulative incidence of
recurrent stroke was 2.02% in the PFO closure arm and 4.4% in the medical therapy
group (RR 0.42, 95%CI 0.20, 0.91; P = 0.03). There was no difference in the
incidence of death [0.7% vs. 0.9%; RR 0.76 (95% CI 0.35, 1.64), P = 0.49] or
adverse events during the follow-up period [24.6% vs. 23.7% (RR 1.03; 95% CI
0.91, 1.16), P = 0.65] between the closure and medical therapy groups. Incidence
of atrial fibrillation was significantly higher in closure group compared to
medical therapy [4% vs. 0.6% (RR 4.73; 95% CI 2.09, 10.70), P = 0.0002]. The
comparative effectiveness of PFO closure (compared to medical therapy) was
significantly more pronounced in those younger than 45 years, males, larger
shunts and disc design platforms (P < 0.05). CONCLUSIONS: Based on the results of
this analysis of randomized trial data, percutaneous PFO closure appears to be a
safe and effective therapeutic option for the secondary prevention of ischemic
stroke in patients with PFO and cryptogenic stroke.
PMID- 29332309
TI - How leaves of mycoheterotrophic plants evolved - from the view point of a
developmental biologist.
AB - How mycoheterotrophs have evolved and how they are sustained are enigmas.
Structural analyses of the plastid genome and phylogenetic analyses of
mycoheterotrophs have been used to identify mycorrhizal fungi. Molecular genetic
studies have also revealed the mechanism for plant-fungi interactions. However,
the evolution of the small, scale-like vegetative leaves of mycoheterotrophs is
unknown. As almost all genes determining leaf size affect the floral organ sizes,
it is highly implausible that loss-of-function mutations in leaf size regulators
caused the evolution of smaller foliage leaves in mycoheterotrophs. In this
Viewpoint, possible evolutionary scenarios of scale-like leaves in
mycoheterotrophs are discussed from the perspective of developmental genetics of
leaves in model plants, including: vegetative phase-specific changes in
expression of leaf size regulator(s); the change from foliage leaves to scale
like lateral organs; and expression of suppressor(s) involved in organ
development. These possibilities can be tested in future studies. This approach
will provide a new research field in the developmental biology of plants.
PMID- 29332310
TI - Advances and current challenges in calcium signaling.
AB - Content Summary 414 I. Introduction 415 II. Ca2+ importer and exporter in plants
415 III. The Ca2+ decoding toolkit in plants 415 IV. Mechanisms of Ca2+ signal
decoding 417 V. Immediate Ca2+ signaling in the regulation of ion transport 418
VI. Ca2+ signal integration into long-term ABA responses 419 VII Integration of
Ca2+ and hormone signaling through dynamic complex modulation of the
CCaMK/CYCLOPS complex 420 VIII Ca2+ signaling in mitochondria and chloroplasts
422 IX A view beyond recent advances in Ca2+ imaging 423 X Modeling approaches in
Ca2+ signaling 424 XI Conclusions: Ca2+ signaling a still young blooming field of
plant research 424 Acknowledgements 425 ORCID 425 References 425 SUMMARY:
Temporally and spatially defined changes in Ca2+ concentration in distinct
compartments of cells represent a universal information code in plants. Recently,
it has become evident that Ca2+ signals not only govern intracellular regulation
but also appear to contribute to long distance or even organismic signal
propagation and physiological response regulation. Ca2+ signals are shaped by an
intimate interplay of channels and transporters, and during past years important
contributing individual components have been identified and characterized. Ca2+
signals are translated by an elaborate toolkit of Ca2+ -binding proteins, many of
which function as Ca2+ sensors, into defined downstream responses. Intriguing
progress has been achieved in identifying specific modules that interconnect Ca2+
decoding proteins and protein kinases with downstream target effectors, and in
characterizing molecular details of these processes. In this review, we reflect
on recent major advances in our understanding of Ca2+ signaling and cover
emerging concepts and existing open questions that should be informative also for
scientists that are currently entering this field of ever-increasing breath and
impact.
PMID- 29332311
TI - Otolaryngology/head and neck region manifestations of Brucella.
AB - OBJECTIVES/HYPOTHESIS: Patients with Brucella infection present with nonspecific
symptoms originating from different organs. In this study, we investigated the
manifestations involving principally the otolaryngology/head and neck region.
STUDY DESIGN: Retrospective cohort chart review. METHODS: A retrospective
analysis of patients diagnosed with brucellosis in a tertiary medical center.
Medical records of 55 patients treated for positive Brucella blood cultures
between 2007 and 2016 were analyzed. Clinical manifestations localized to the
otolaryngology/head and neck region were evaluated. RESULTS: Most patients (78%)
in our study group lived in rural areas. There was an almost equal gender
distribution and a wide age range (2-77 years). Nonspecific symptoms, including
fever (71%), fatigue (31%), weight loss (20%), and night sweats (32.7%) were the
most common. Of the specific organ systems affected by Brucella, the
osteoarthritic system was most commonly infected (45.5%). Three patients (5.5%)
presented with predominantly localized otolaryngology/head and neck region
symptoms, consisting of necrotic lymphadenopathy or a thyroid abscess. All
patients underwent drainage procedures, and the diagnosis was confirmed by
positive blood and pus cultures. Complete resolution was achieved with prolonged
antibiotic treatment. CONCLUSIONS: Brucella infection should be suspected in
patients with nonspecific constitutional symptoms associated with neck
lymphadenopathy or thyroid abscess, especially in those living in rural areas. A
high index of suspicion is mandatory for proper diagnosis and treatment. Formal
drainage and prolonged antibiotic treatments are required. We strongly recommend
simple drainage and not excision as the mainstay of surgical treatment. LEVEL OF
EVIDENCE: 4. Laryngoscope, 128:2056-2059, 2018.
PMID- 29332312
TI - Corrigendum.
PMID- 29332314
TI - New year's greetings: International Journal of Urology celebrates 25 years.
PMID- 29332315
TI - Comparison of treatment strategies for femoro-popliteal disease: A network meta
analysis.
AB - OBJECTIVES: We sought to compare treatment strategies in a Bayesian network meta
analysis of randomized controlled trials. BACKGROUND: Peripheral artery disease
(PAD) is a prevalent morbidity that is treated with various strategies. METHODS:
We performed a MEDLINE search for randomized studies comparing at least 2
treatment strategies, including bypass surgery, percutaneous transluminal
angioplasty (PTA) balloons, stents, covered stents, drug-eluting stents (DES),
and drug-coated balloons (DCB), in patients with native femoro-popliteal disease.
Mixed treatment comparison model generation was performed to directly and
indirectly compare the strategies in terms of restenosis and target lesion
revascularization (TLR) presented as odds ratios (OR, [95% credible intervals]).
RESULTS: Twenty-nine studies with 4,820 patients were included in the present
study. PTA was the largest group with 1,900 patients, followed by DCB (n =
1,343), bare metal stents (n = 941), covered stents (n = 304), DES (n = 236), and
bypass (n = 92). Mean age was 68 +/- 9 years, 64% were male, 37% diabetic, and
55% smokers. Mean lesion length was 77 +/- 44 mm, and 39% were total occlusions.
Bayesian hierarchical random-effects model demonstrated all treatments were
significantly better than, or had a trend toward superiority over, PTA, with DCB
ranking well in both restenosis (OR = 0.29, [0.17-0.47]) and TLR (OR = 0.31,
[0.20-0.46]). Nonetheless, none of the therapies showed superiority in terms of
survival or amputations. CONCLUSION: Treatment of femoro-popliteal disease has
significantly evolved in recent years, with higher rates of patency and freedom
from TLR. However, the utility of these treatment strategies in terms of
reduction of amputations and overall survival remains in question.
PMID- 29332316
TI - How do I implement a whole blood program for massively bleeding patients?
AB - Building on the successful military experience, interest has been rekindled in
transfusing whole blood (WB) early in the resuscitation of traumatically injured
civilians, often before their ABO group is known. WB efficiently provides
treatment for shock and coagulopathy, as well as platelet hemostatic function, to
patients losing large volumes of blood. Unlike group O uncrossmatched red blood
cells (RBCs), group O WB contains a substantial amount of plasma, which is
incompatible with the RBCs of all non-group O recipients. Thus, when implementing
a WB program, it is important to decide how to mitigate the risk of immune
mediated hemolysis. Other questions that a hospital needs to answer before
implementing a WB program include determining which patients will be eligible for
this product, how many units eligible patients can receive, for how long it
should be stored and under what conditions, and how to monitor for adverse
events. The donor center needs to consider if the WB should be leukoreduced, how
to comply with the AABB's transfusion-related acute lung injury risk mitigation
standard, and into which storage solution it should be collected. This report
describes the multidisciplinary approach taken to implementing a civilian WB
program at a multihospital health care system in the United States.
PMID- 29332317
TI - Routine use of Day 6 and Day 7 platelets with rapid testing: two hospitals assess
impact 1 year after implementation.
AB - BACKGROUND: In March 2016 the US Food and Drug Administration published a draft
guidance to enhance the safety of platelets (PLTs) for transfusion. Options for
hospital transfusion services include the use of rapid testing to extend
apheresis PLT dating for up to 7 days. This report describes the impact of
routine use of Day 6 and Day 7 PLTs at two hospital transfusion services 1 year
after implementation of rapid testing for outdate extension. STUDY DESIGN AND
METHODS: PLT transfusion and inventory data were obtained from two hospital-based
transfusion services for 12 months before and 12 months after implementation of
rapid testing to extend the outdate of apheresis PLTs to 7 days. RESULTS: The
outdate rate decreased from 5% to 2% (p < 0.0001) at Hospital 1 and 28% to 14% (p
< 0.001) at Hospital 2 after implementation of routine use of Day 6 and Day 7
PLTs. The proportion of apheresis PLT units that underwent secondary screening
for bacterial contamination before transfusion in the postimplementation period
increased from 33% to 54% at Hospital 1 and from 0% to 31% at Hospital 2.
CONCLUSION: A significant decrease in outdate rate was observed after routine use
of Day 6 and Day 7 PLTs. Use of rapid testing to extend PLT outdate also resulted
in a larger proportion of PLTs that underwent secondary testing for bacterial
contamination before transfusion. These observations demonstrate that use of
rapid testing to extend apheresis PLT dating up to 7 days enhances the safety of
PLTs for transfusion and decreases wastage of a limited resource.
PMID- 29332318
TI - Intraspecific differences in plant defense induction by fall armyworm strains.
AB - The underlying adaptive mechanisms by which insect strains are associated with
specific plants are largely unknown. In this study, we investigated the role of
herbivore-induced defenses in the host plant association of fall armyworm
(Spodoptera frugiperda) strains. We tested the expression of herbivore-induced
defense-related genes and the activity of plant-defensive proteins in maize and
Bermuda grass upon feeding by fall armyworm strains. The rice strain caterpillars
induced greater accumulation of proteinase inhibitors in maize than the corn
strain caterpillars. In Bermuda grass, feeding by the corn strain suppressed
induction of trypsin inhibitor activity whereas the rice strain induced greater
activity levels. Differences in elicitation of these plant defenses by the two
strains seems to be due to differences in the activity levels of the salivary
enzyme phospholipase C. The levels of plant defense responses were negatively
correlated with caterpillar growth, indicating a fitness effect. Our results
indicate that specific elicitors in the saliva of fall armyworm stains trigger
differential levels of plant defense responses that affect caterpillar growth and
thus may influence host plant associations in field conditions. The composition
and secretion of plant defense elicitors may have a strong influence in the host
plant association of insect herbivores.
PMID- 29332319
TI - Treatment of Latent Tuberculosis Infection and Its Clinical Efficacy.
AB - The role of the treatment for latent tuberculosis infection (LTBI) has been
underscored in the intermediate tuberculosis (TB) burden countries like South
Korea. LTBI treatment is recommended only for patients at risk for progression to
active TB-those with frequent exposure to active TB cases, and those with
clinical risk factors (e.g., immunocompromised patients). Recently revised
National Institute for Health and Care Excellence (NICE) guideline recommended
that close contacts of individuals with active pulmonary or laryngeal TB, aged
between 18 and 65 years, should undergo LTBI treatment. Various regimens for LTBI
treatment were recommended in NICE, World Health Organization (WHO), and Centers
for Disease Control and Prevention guidelines, and superiority of one recommended
regimen over another was not yet established. Traditional 6 to 9 months of
isoniazid (6H or 9H) regimen has an advantage of the most abundant evidence for
clinical efficacy-60%-90% of estimated protective effect. However, 6H or 9H
regimen is related with hepatotoxicity and low compliance. Four months of
rifampin regimen is characterized by less hepatotoxicity and better compliance
than 9H, but has few evidence of clinical efficacy. Three months of isoniazid
plus rifampin was proved equivalence with 6H or 9H regimen in terms of efficacy
and safety, which was recommended in NICE and WHO guidelines. The clinical
efficacy of isoniazid plus rifapentine once-weekly regimen for 3 months was
demonstrated recently, which is not yet introduced into South Korea.
PMID- 29332320
TI - The Role of Tiotropium+Olodaterol Dual Bronchodilator Therapy in the Management
of Chronic Obstructive Pulmonary Disease.
AB - Bronchodilator therapy is central to the management of chronic obstructive
pulmonary disease and are recommended as the preferred treatment by the Global
Obstructive Lung Disease Initiative (GOLD). Long acting anti-muscarinics (LAMA)
and long acting beta2 agonists (LABA) are both more effective than regular short
acting drugs but many patients remain symptomatic despite monotherapy with these
drugs. Combination therapy with LAMA and LABA increases the therapeutic benefit
while minimizing dose-dependent side effects of long-acting bronchodilator
therapy. The TOviTO programme has investigated the benefits of treatment with a
combination of tiotropium and olodaterol administered via a single inhaler.
Tiotropium+olodaterol 5/5 MUg significantly improved forced expiratory volume in
1 second (FEV1) area under the curve from 0 to 3 hours, trough FEV1 health status
and breathlessness versus the mono-components and placebo. Tiotropium+olodaterol
5/5 MUg also increased endurance time and reduced dynamic hyperinflation during
constant work rate cycle ergometry. On the basis of these and other studies the
2017 GOLD report recommends escalating to dual bronchodilator therapy in patients
in groups B and C if they remain symptomatic or continue to have exacerbations
and as initial therapy for patients in group D.
PMID- 29332321
TI - Indicators and Qualitative Assessment of Lung Cancer Management by Health
Insurance Review and Assessment Service (HIRA) of Korea in 2015.
AB - Cancer is the leading cause of death in the Republic of Korea and cancer death
accounts for 27.8% of the total deaths, which is not only a social issue but also
a concern for the public. Among the cancer death rates, lung cancer mortality
account for 34 deaths per 100,000 populations, making it the number one cancer
death rate. In a preliminary report on cancer death in 2012, the lung cancer
mortality ratio showed the regional variation indicating that there were
differences in the qualitative level and the structure among the medical care
benefit agency and in the assessment of the treatment process. Therefore, the
Health Insurance Review and Assessment Service (HIRA) had begun evaluation of the
assessment of lung cancer treatment since 2014 to improve the quality of lung
cancer care through evaluation and feeds back the results of lung cancer care
process. In this report, authors described the current Indicators for the lung
cancer adequacy assessment proposed by HIRA and results of the evaluation
reported in 2017.
PMID- 29332322
TI - Tumor Immunology and Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer.
AB - Lung cancer is one of the most commonly diagnosed cancers and the leading cause
of cancer-related deaths worldwide. Although progress in the treatment of
advanced non-small cell lung cancer (NSCLC) has been made over the past decade,
the 5-year survival rate in patients with lung cancer remains only 10%-20%.
Obviously, new therapeutic options are required for patients with advanced NSCLC
and unmet medical needs. Cancer immunotherapy is an evolving treatment modality
that uses a patient's own immune systems to fight cancer. Theoretically, cancer
immunotherapy can result in long-term cancer remission and may not cause the same
side effects as chemotherapy and radiation. Immuno-oncology has become an
important focus of basic research as well as clinical trials for the treatment of
NSCLC. Immune checkpoint inhibitors are the most promising approach for cancer
immunotherapy and they have become the standard of care for patients with
advanced NSCLC. This review summarizes basic tumor immunology and the relevant
clinical data on immunotherapeutic approaches, especially immune checkpoint
inhibitors in NSCLC.
PMID- 29332323
TI - Development of Prediction Equation of Diffusing Capacity of Lung for Koreans.
AB - BACKGROUND: The diffusing capacity of the lung is influenced by multiple factors
such as age, sex, height, weight, ethnicity and smoking status. Although a
prediction equation for the diffusing capacity of Korea was proposed in the mid
1980s, this equation is not used currently. The aim of this study was to develop
a new prediction equation for the diffusing capacity for Koreans. METHODS: Using
the data of the Korean National Health and Nutrition Examination Survey, a total
of 140 nonsmokers with normal chest X-rays were enrolled in this study. RESULTS:
Using linear regression analysis, a new predicting equation for diffusing
capacity was developed. For men, the following new equations were developed:
carbon monoxide diffusing capacity (DLco)=-10.4433-0.1434*age
(year)+0.2482*heights (cm); DLco/alveolar volume (VA)=6.01507-0.02374*age (year)
0.00233*heights (cm). For women the prediction equations were described as
followed: DLco=-12.8895-0.0532*age (year)+0.2145*heights (cm) and DLco/VA=7.69516
0.02219*age (year)-0.01377*heights (cm). All equations were internally validated
by k-fold cross validation method. CONCLUSION: In this study, we developed new
prediction equations for the diffusing capacity of the lungs of Koreans. A
further study is needed to validate the new predicting equation for diffusing
capacity.
PMID- 29332325
TI - Is alpha-N-acetylgalactosaminidase the key to curing cancer? A mini-review and
hypothesis.
AB - In the constant battle against cancer cells, macrophages are of great importance.
Their activation is achieved through various mechanisms such as Vitamin D binding
protein (VDBP or Gc). After undergoing modifications via enzymes secreted by
stimulated lymphocytes, VDBP is modified into Macrophages Activator Form/Factor
(Gc-MAF). Some studies (particularly those focusing on cancer) have reported that
an enzyme known as alpha-N-acetylgalactosaminidase (nagalase) facilitates the
deglycosylation of Gc-MAF, which in turn inhibits the activation of macrophages.
The aim of this review was to evaluate studies associated with nagalase and its
escalation in various diseases and to propose hypothetical solutions in order to
neutralize the effects of nagalase in cancer patients.
PMID- 29332324
TI - Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model.
AB - BACKGROUND: Asthma is a disease of chronic airway inflammation with heterogeneous
features. Neutrophilic asthma is corticosteroid-insensitive asthma related to
absence or suppression of TH2 process and increased TH1 and/or TH17 process.
Macrolides are immunomodulatory drug that reduce airway inflammation, but their
role in asthma is not fully known. The purpose of this study was to evaluate the
role of macrolides in neutrophilic asthma and compare their effects with those of
corticosteroids. METHODS: C57BL/6 female mice were sensitized with ovalbumin
(OVA) and lipopolysaccharides (LPS). Clarithromycin (CAM) and/or dexamethasone
(DXM) were administered at days 14, 15, 21, 22, and 23. At day 24, the mice were
sacrificed. RESULTS: Airway resistance in the OVA+LPS exposed mice was elevated
but was more attenuated after treatment with CAM+DXM compared with the
monotherapy group (p<0.05 and p<0.01). In bronchoalveolar lavage fluid study,
total cells and neutrophil counts in OVA+LPS mice were elevated but decreased
after CAM+DXM treatment. In hematoxylin and eosin stain, the CAM+DXM-treated
group showed less inflammation additively than the monotherapy group. There was
less total protein, interleukin 17 (IL-17), interferon gamma, and tumor necrosis
factor alpha in the CAM+DXM group than in the monotherapy group (p<0.001, p<0.05,
and p<0.001). More histone deacetylase 2 (HDAC2) activity was recovered in the
DXM and CAM+DXM challenged groups than in the control group (p<0.05). CONCLUSION:
Decreased IL-17 and recovered relative HDAC2 activity correlated with airway
resistance and inflammation in a neutrophilic asthma mouse model. This result
suggests macrolides as a potential corticosteroid-sparing agent in neutrophilic
asthma.
PMID- 29332326
TI - Carcinogenic potential of antitumor therapies - is the risk predictable?
AB - The growing number of successfully cured cancer patients has created a new field
in oncogenesis. The life expectancy of such patients has increased, however this
favorable event may create enough time for epigenetic events to occur which can
cause a new carcinognic event, i.e. a secondary malignancy. The terms in use are
second primary malignancies as well as therapy-related neoplasms in case the
treatment of the first neoplasm is a direct cause. Second primary malignancies
can be hematological neoplasms or solid tumors, with solid tumors having higher
frequency. Hematological malignancies, especially t MDS (therapy-related
myelodysplastic syndrome) and t AML (therapy-related acute myeloid leukemia), are
causally associated with cytotoxic chemotherapy, while secondary solid tumors are
related to radiotherapy. The pathogenic mechanisms of clonal selection in second
malignancies are in connection with induction of fusion oncogenes, induction of
genetic instability, selection of resistant cell clones and hereditary
predisposition. The most common oncogenic agents are external (antineoplastic
systemic treatments including radiation therapy), patient-specific factors
(genetic, demographic, hormonal) and tumorspecific factors (tissue
radiosensitivity, immunodeficiency). There are special features in the clinical
picture, biological characteristics and evolution of the second neoplasm -
different latency period, aggressive course and treatment resistance. Risks,
types and characteristics of secondary malignancies are analyzed in specific
groups of patients. For example, the peak of t-AML is several years after a
primary malignancy and for solid tumors, the risk increases progressively during
the observation period. In this review, the authors outline that the risk of
second malignancies is predictable and can be controllable by adequate monitoring
of patients as well as by personalized treatment of the first neoplasm.
PMID- 29332327
TI - Stage-II thymoma and emergency coronary artery bypass. To irradiate or not to
irradiate to avoid radiation induced vascular injury? Case report and literature
review.
AB - PURPOSE: The purpose of this study was to present the controversial role of
adjuvant radiotherapy to a 72-year-old male patient with Masaoka stage II thymoma
and coronary artery bypass and to review the relevant literature. METHODS: The
data were collected by relevant studies on PubMed and EMBASE. Articles up to
March 2017 were included. RESULTS: Although the radiation-induced vascular injury
to the internal thoracic artery and its suitability for grafting in a patient who
is candidate for coronary artery bypass is documented, the possible catastrophic
effect of adjuvant radiotherapy to existing grafts in a patient with prior bypass
surgery has not been fully investigated. CONCLUSION: The application of
radiotherapy in a patient with R0 stage II thymoma is currently considered of 2B
level of evidence but its potential occlusive effect to an underlying coronary
graft may dramatically affect the survival of the patient and accordingly drop
the level of evidence of its use.
PMID- 29332328
TI - Carcinoembryonic antigen and carbohydrate antigen 19-9 serum levels in non-small
cell lung cancer.
AB - PURPOSE: Tauo investigate the potential diagnostic and prognostic role of
carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) serum
levels in non-small cell lung cancer (NSCLC). METHODS: One hundred consecutive
patients with newly diagnosed primary NSCLC were included in this study (88 men
and 12 women). Blood was drawn before any kind of treatment and the collected
serum was processed using chemiluminescence in order CEA and CA 19-9 levels to be
measured. RESULTS: No significant associations between CEA or CA 19-9 levels and
any tested clinical and pathological parameter were detected. Moreover, CEA
levels did not seem to affect survival. On the other hand, patients with high CA
19-9 values (>=37 IU/ml) (median survival: 8 months) had a shorter overall
survival than patients with low CA 19-9 values (<37 IU/ml) (median survival: 13
months) (p=0.026). However, CA 19-9 levels did not remain an independent
prognostic factor in the multivariate survival analysis (p=0.114). CONCLUSION:
CEA and CA 19-9 serum levels do not seem to have any diagnostic role in NSCLC.
With regard to their prognostic role, CEA values do not seem to affect the
prognosis in NSCLC. However, high CA 19-9 values are associated with worse
prognosis.
PMID- 29332329
TI - Modified 3-week schedule of gemcitabine plus cisplatin for non-small cell lung
cancer treatment.
AB - PURPOSE: Gemcitabine-cisplatin combination is one of the most used schedules for
non small cell lung cancer (NSCLC). Aiming to enhance dose intensity and reduce
toxicity, the original 4-week schedule was modified or transformed into a 3-week
schedule. The purpose of this study was to report the efficacy and tolerability
of a modified 3-week regimen of gemcitabine-cisplatin. METHODS: Our patients were
treated with gemcitabine (1000 mg7sol;m2) on days 1, 8 and cisplatin on day 8 (75
100 mg/m2). The toxicity was recorded according to the NCIC criteria. RESULTS:
From October 2000 to December 2009 a consecutive series of 196 patients with a
median age of 62 years and III-IV stage NSCLC received gemcitabine-cisplatin as
induction therapy (76 patients) or palliative treatment (120 patients). The
median dose intensity was 89%. In relation to day 8 of chemotherapy, 16.2% of the
treatments were delayed due to hematologic toxicities. Grade 3-4 anaemia,
neutropenia and thrombocytopenia was reported in 3.5, 43.8 and 4.6%,
respectively. Response rate (RR) and median overall survival (OS) were 74% and 11
months in patients with locally advanced disease, and 46.7% and 9 months in
metastatic patients, respectively. CONCLUSIONS: In comparison with standard or
modified schedules of literature, our modified 3-week regimen of gemcitabine-
cisplatin demonstrated to be equally active, similar for dose intensity and well
tolerated, with better hematologic toxicity profile in terms of anaemia and
thrombocytopenia.
PMID- 29332330
TI - Therapeutic effect of gefitinib in advanced non-small cell lung cancer and its
effect on the EGFR level in peripheral blood.
AB - PURPOSE: This study was designed to investigate the therapeutic effect of
gefitinib in advanced non-small cell lung cancer (NSCLC) and its effect on the
level of epidermal growth factor receptor (EGFR) in peripheral blood. METHODS: A
total of 58 patients with NSCLC were treated with gefinitib (iressa) (250 mg per
day). EGFR levels in the peripheral blood were measured with ELISA assay before
and after treatment. Statistical analyses of patient quality of life, survival
and other clinical data were conducted including logistic regression analysis, x2
test and t-test. Quality of life assessment was quantified based on the Chinese
version of the QLQ-C30 and QLQ-LC13 questionnaires of the European Organization
for Research and Treatment of Cancer. RESULTS: The overall response rate to
iressa was 38% (22 patients), and the disease control rate (response+stable) was
74% (43 patients). The mean scores of assessment of physiological functions and
comprehensive quality of life in QLQ-C30 questionnaire were significantly
increased with an improvement rate of 91-100%. Similarly, the mean scores of
assessment of disease symptoms in QLQ-LC12 questionnaire were significantly
reduced with an overall improvement rate of 73-100). Adverse drug effects were
mainly grade I and II skin rashes and diarrhea. The EGFR levels in peripheral
blood were significantly decreased after treatment (p<0.05). CONCLUSION: Based on
our results, gefitinib showed meaningful effects in treating advanced NSCLC,
significantly improving clinical symptoms and ameliorating the patient quality of
life.
PMID- 29332331
TI - EGFR mutations and tumor metastases in patients with nonsmall cell lung cancer in
the South of Russia.
AB - PURPOSE: To assess the frequencies of somatic EGFR mutations in the tumor tissues
of patients with non-small cell lung cancer (NSCLC) residing in the South of
Russia (SR), and to define the relationship between genetic subtypes of NSCLC and
the emergence of different types of metastases. METHODS: DNA was extracted from
formalin-fixed parrafin embedded (FFPE) samples of 721 patients. A total of 29
somatic EGFR mutations were detected using commercial Therascreen EGFR RGQ PCR
Kit. RESULTS: EGFR mutations were significantly more frequent in females and non
smokers even when considering the combination of both factors. The frequency of
activating EGFR mutations across three age groups (<51, 51-61, >61 years) of
women with NSCLC was significantly different (x2=10.94, p=0.004) and became
higher with increasing age. Both activating and resistance mutations of EGFR were
not associated with the frequency of regional or distant metastases. The
frequencies of both regional and distant metastases were associated with higher
disease stage (odds ratio/OR)=16.71; 95% confidence interval (CI): 9.5-29.38;
p<0.0001, and OR=2.94; 95% CI: 2.22-3.88; p<0.0001, respectively) and
adenocarcinona histology (OR=6.52; 95% CI: 2.03-20.92; p=0.002, and OR=1.99; 95%
CI: 0.91-4.34; p=0.083, respectively) even when adjusted for age, gender, and
smoking status. The risk for regional metastases development was associated with
poor tumor differentiation (OR=2.91; 95% CI: 1.21-7.02; p=0.017). CONCLUSION:
EGFR mutations were not associated with the frequency of regional or distant
metastases in SR patients with NSCLC.
PMID- 29332332
TI - A study on cellular immune function of patients treated with radical resection of
pulmonary carcinoma with two different methods of anesthesia and analgesia.
AB - PURPOSE: To compare the influence on the immune system of two different methods
of anesthesia and analgesia in patients treated with radical resection of
pulmonary carcinoma. METHODS: Thirty-four patients treated with radical resection
of pulmonary carcinoma were randomly divided into two groups (group A and group
B, 17 cases in each group). Patients in group A were administered total
intravenous anesthesia (TIVA) without inhaled hypnotics and intravenous analgesia
while patients in group B were administered TIVA combined with epidural
anesthesia and epidural analgesia. We compared changes of the T cells subsets
(CD3+, CD4+, CD8+ and CD4+/CD8+ ratio) and the function of natural killer (NK)
cells in patients at 4 time points: before anesthesia, immediately after surgery,
24 hrs after surgery and 72 hrs after surgery. Clinical data were also collected.
RESULTS: CD8+ in group A and B was significantly increased (p<0.01) while the
other indexes CD3+, CD4+, CD4+/CD8+ ratio and NK cells) were significantly
decreased (p<0.05). There was a significant difference in various indexes (except
NK cell) before anesthesia and 72 hrs after surgery in group A (p<0.01). Various
indexes of patients in group B at 72 hrs after surgery were restored to the
values before anesthesia (p>0.05). We observed a significant difference in CD3+,
CD8+ and CD4+/CD8+ indexes in groups A and B patients at 72 hrs after surgery
(p<0.05). CONCLUSIONS: TIVA combined with epidural anesthesia and epidural
analgesia demonstrated less interference with the immune system and determine
fast recovery in patients with radical resection of pulmonary carcinoma.
PMID- 29332333
TI - Epigallocatechin gallate from green tea exhibits potent anticancer effects in A
549 non-small lung cancer cells by inducing apoptosis, cell cycle arrest and
inhibition of cell migration.
AB - PURPOSE: Green tea (Camellia sinensis) is considered as a rich source of
epigallocatechin gallate (EGCG) which has been shown to exert impressive
pharmacological properties. The anticancer properties of EGCG have been
extensively studied however, its anticancer activity has not been explored in
lung cancer. The present study was therefore designed to evaluate the anticancer
effects of EGCG against non-small cell lung cancer (NSCLC) cell line A-549 and
normal human fibroblast FR-2 cells. METHODS: Cell viability was assessed by CCK8
assay, apoptosis by DAPI, annexin V/propidium iodide (PI) and flowcytometery and
cell cycle analysis by flow cytometry. Cell migration capacity was investigated
by wound-healing assay and protein expression was examined by Western blotting.
RESULTS: The results revealed that EGCC could inhibit the proliferation of A-549
cells in a concentration-dependent manner and exhibited an IC50 of 25 MUM against
the IC50 of 100 MUM against the normal human fibroblasts. Further evaluation
revealed that EGCG exerts its anticancer effects via induction of apoptosis,
modulation of Bax/blc-2 ratio and by triggering G2/M cell cycle arrest.
Furthermore, EGCG could also inhibit the migration of A5-49 cells in a
concentration-dependent manner. CONCLUSION: In conclusion, based on our results,
we believe that EGCG could prove to be an important lead molecule for the
treatment of lung cancer.
PMID- 29332334
TI - MiR429 expression level in renal cell cancer and its correlation with the
prognosis of patients.
AB - PURPOSE: To test the hypothesis that miR429 expression in renal cancer patients
is increased and plays a role in the pathogenesis of the disease. METHODS: Twenty
seven renal cancer patients admitted to our hospital from May 2014 to May 2015
were enrolled as the study group, and 28 non-cancer patients were selected during
the same period as the control group. Renal biopsy and serum samples were used to
detect miR429 expression levels, and the patient histories were obtained to make
relevant associations to clinical outcomes. In addition, the renal cancer cell
line SK458 was used for overexpressing or knocking out miR429 in in vitro
experiments to observe changes in proliferation and apoptosis rates. RESULTS: The
expression levels of miR429 in renal tissues and serum of renal cancer patients
were significantly higher compared with control patients (p<0.05). In addition, a
correlation was found between the levels of miR429 in the serum of renal cell
cancer patients and their clinical outcome after conventional treatment, with
patients expressing lower miR429 levels showing better clinical outcomes.
Finally, experiments with renal cancer cells revealed that the proliferation of
cells overexpressing miR429 was increased and their apoptosis rate was
significantly reduced, while the opposite was true in miR429-knockout cells.
CONCLUSIONS: It seems that miR429 can inhibit normal apoptosis rates and lead to
high proliferation rates. Accordingly, the higher serum miR429 level in renal
cancer patients suggests that it plays a role in the pathogenesis of the disease,
while the differential miR429 levels according to the patients' clinical outcomes
after treatment suggest that miR429 may be useful as a marker for prognosis.
PMID- 29332335
TI - Clinicopathological characteristics and survival in Serbian patients with renal
cell carcinoma: a retrospective analysis.
AB - PURPOSE: Indications of kidney cancer outcome in lowerincome countries are based
on an incidence/mortality ratio due to lack of survival information. This study
was conducted to provide outcome data in Serbian patients with renal cell
carcinoma (RCC) and to identify prognostic factors that could affect their
overall survival (OS). METHODS: This retrospective study included 185 patients
who underwent nephrectomy. We assessed certain clinicopathological data including
age, gender, tumor size, grade, stage and histological subtypes for their
possible impact on OS. RESULTS: The 5-year OS was 63.2%. Significant association
was found between OS and age (log-rank 12.455, p=0.006), tumor size (log-rank
26.425, p=0.000), grade (log-rank 13.249, p=0.000) and stage (log-rank 43.235,
p=0.000). Univariate analysis indicated size (p=0.000), grade (p=0.001) and stage
(p=0.000) as prognostic factors for OS. In multivariate analysis, grade (p=0.014)
and stage (p=0.000) remained significant predictors of OS. CONCLUSION: Tumor
grade and stage were identified as independent prognostic factors of OS survival
in Serbian patients with RCC.
PMID- 29332336
TI - Downregulation of guanine nucleotide-binding protein beta 1 (GNB1) is associated
with worsened prognosis of clearcell renal cell carcinoma and is related to VEGF
signaling pathway.
AB - PURPOSE: Clear-cell renal cell carcinoma (ccRCC) is characterized by genetic
abnormalities, while the role of Guanine Nucleotide-Binding Protein Beta 1 (GNB1)
in ccRCC has not been studied. We thus aimed to evaluate the expression and
prognostic value of GNB1 in ccRCC. METHODS: A two-stage study (exploration and
validation) was conducted using in silico and immunohistochemical (IHC) scoring
of ccRCC samples from our institute, to evaluate the association between GNB1
expression and clinicopathological parameters of ccRCC patients. Pathway analyses
were performed for genes coexpressed with GNB1 using the KOBAS platform to
profile the function of GNB1 and IHC validation. RESULTS: In the exploration
stage, data from TCGA ccRCC dataset were reproduced, which contained 537 patients
with ccRCC and found that downregulation of GNB1 was significantly associated
with worse prognosis. IHC staining from the Human Protein Atlas showed
significantly downregulation of GNB1 in ccRCC tissue compared with normal kidney.
Pathway analysis showed significantly altered vascular endothelial growth factor
(VEGF) signaling pathways among which expressions of 3 genes (WASF2, NRP1, and
HIP1) were significantly associated with GNB1 expression, respectively. In the
validation stage, included were 80 ccRCC samples and GNB1 expression was scored
using IHC positivity. GNB1 expression was negatively associated with tumor stage,
lymph node invasion, metastasis, older age, and increased tumor grade. Female
gender and receiving neoadjuvant therapy were also associated with decreased GNB1
expression. The expressions of WASF2, NRP1 and HIP1 were also studied and found
that they were significantly associated with GNB1. CONCLUSION: GNB1 was
downregulated in ccRCC. Decreased GNB1 expression was associated with worsened
disease characteristics and prognosis. GNB1 was related with VEGF signaling in
ccRCC, implying a therapeutic potential of this factor.
PMID- 29332337
TI - Systemic treatment and primary tumor location in patients with metastatic
colorectal cancer.
AB - PURPOSE: Tumor location (right-sided vs. left-sided) is known to exert a
significant influence on the prognosis of primary colorectal cancer (CRC). Given
the genetic continuity between primary and metastatic lesions, we aimed to
summarize the existing literature on the prognostic implications of primary tumor
site as well as to examine the response to chemotherapy by primary tumor location
in patients with metastatic CRC (mCRC). METHODS: A structured review of the
literature was performed between 6/1/2016-7/1/2016 using the Pubmed database.
Original research articles published between 1/1/2000- 07/01/2016 were considered
eligible. The primary endpoints were overall survival (OS)/ progression free
survival (PFS) and response to systemic treatment in patients with mCRC. RESULTS:
Eleven studies were included. Tumor site was a strong independent predictor of
worse OS/PFS in 9 studies, with right-sided tumors having worse prognosis in all
cases. Furthermore, 6 studies demonstrated an inferior response to systemic
treatment or worse prognosis following the administration of specific regimens
among patients with right-sided cancers. As such, there is significant evidence
that right-sided lesions are associated with poor outcomes and resistance to
systemic treatment. CONCLUSION: Consequently, primary tumor location should be a
consideration, when the administration of systemic therapy is contemplated in
mCRC.
PMID- 29332338
TI - X-ray-induced epithelial-mesenchymal transition in SW480 colorectal cancer cells
and its potential mechanisms.
AB - PURPOSE: The purpose of this study was to investigate the relation between X-ray
irradiation and epithelial-mesenchymal transition (EMT), as well as the potential
mechanisms of X-ray-induced EMT in SW480 colorectal cancer (CRC) cells. METHODS:
It is well known that EMT plays a critical role in invasive and metastatic of
colorectal cancer progression. However, the possible role of X-ray irradiation on
EMT in colorectal cancer is widely disputed and its potential mechanisms are
unclear. SW480 CRC were irradiated (0, 2, 4, 6, 8 Gy) and cultured for 48 hrs,
and then the cellular morphology was observed. Protein and mRNA expressions were
examined by Western blot and QRT-PCR. Cell migratory and invasive capacity was
evaluated by Transwell assay. RESULTS: In the 2, 4, 6, 8 Gy groups, SW480 CRC
exhibited a classical mesenchymal phenotype compared with the 0 Gy group. The
expression of E-cadherin was significantly decreased, while the expression of
vimentin and Smad3 was significantly increased in the 2, 4, 6, 8 Gy groups
(p<0.05) compared with the 0 Gy group; still, the expression of K-ras decreased
in the 4, 6, 8 Gy groups (p<0.05) compared with the 0 and 2 Gy groups.
Furthermore, the cell migration and invasion capacity was significantly enhanced
in the 4 and 8 Gy groups compared with the 0 Gy group (p<0.05). CONCLUSION: These
results support the fact that X-ray irradiation can induce EMT through promoting
Vimentin and Smad3 expression in SW480 CRC cells.
PMID- 29332339
TI - p21 does, but p53 does not predict pathological response to preoperative
chemoradiotherapy in locally advanced rectal cancer.
AB - PURPOSE: Preoperative chemoradiotherapy (CRT) is the standard treatment option in
locally advanced rectal cancer. The tumor response is assessed through tumor and
nodal downstaging and the tumor regression grade. Currently, there is no method
to predict a tumor response to CRT. We aimed to evaluate whether p21 and p53
expressions could be a reliable predictors of pathological response to CRT.
METHODS: Fifty patients with locally advanced rectal cancer were treated with
preoperative radiotherapy combined with mitomycin C and capecitabine. p21 and p53
immumohistochemical staining was performed on pretreatment biopsies and the
results were compared with tumor regression according to grading systems by
Dworak (TRG grades) and by Wheeler (RCRG grades). RESULTS: Testing RCRG grades in
relation to p21 expression showed statistically significant difference (p=0.021).
RCRG 3 (poor response) was more frequent in the group of patients with low p21.
According to Dworak, grade 4 (complete regression) was more frequent in the group
of patients with positive p21 expression (p=0.032). Significant difference in p21
expression in grade 4 group compared with all other grade groups was also found
(p=0.007). Patients with immune expression of p21 had significantly higher
percentage of complete regression in comparison to the patients with low
expression of p21. We haven't found any correlation between p53 expression and
histopathological (HP) as well as regression grades. CONCLUSION: According to
both grading systems, our results suggest that p53 expression does not, but p21
expression does predict pathological response to preoperative CRT.
PMID- 29332340
TI - Imperatorin shows selective antitumor effects in SGC-7901 human gastric
adenocarcinoma cells by inducing apoptosis, cell cycle arrest and targeting
PI3K/Akt/m-TOR signalling pathway.
AB - PURPOSE: The main purpose of the present study was to determine the anticancer
properties of imperatorin - a naturally occurring coumarin compound - against SGC
7901 human gastric adenocarcinoma cells and the mouse fibroblast cell line 3T3
(normal cell line). METHODS: Imperatorin effects on apoptosis induction, cell
cycle phase distribution and PI3K/Akt/m-TOR signalling pathways were studied. MTT
cell viability assay examined the compound's cytotoxic potential, while inverted
phase contrast microscopy and fluorescence microscopy techniques were used to
study morphological changes induced in SGC-7901 cells by imperatorin. Flow
cytometry examined its effects on cell cycle progression while Western blot assay
was used to study changes in protein expressions of PI3K/Akt/m-TOR pathway.
RESULTS: Imperatorin induced a dose-dependent growth inhibition of the SGC-7901
gastric cancer cells with an IC50 value 62.6 MUM, while in case of normal 3T3
mouse fibroblast cells, the drug did not show significant toxicity (IC50 value
195.8 MUM), indicating that the drug selectively induced cytotoxicity in gastric
cancer cells. The cells became rounded up, shrunken in size and got detached from
the monolayer attached to well surface. Cells treated with 10, 75 and 175 MUM
imperatorin indicated that they began to emit yellow or red fluorescence which is
an indication of early or late apoptosis respectively. Imperatorin also induced
significant DNA fragmentation along with increasing the fraction of sub-G1 cells,
indicating a sub-G1 cell cycle arrest. CONCLUSION: Imperatorin could prove an
important lead molecule for the treatment of gastric cancer and deserves further
research in vivo against more cell lines.
PMID- 29332341
TI - Association of the combined parameters including the frequency of primary cilia,
CD8+ tumor infiltrating lymphocytes and PD-1 expression with the outcome in
intestinal cancer.
AB - PURPOSE: Primary cilium (PC) is considered to be a functional homologue of the
immune synapse. Microtubule structures, PC of cancer associated fibroblasts and
immune synapses between cytotoxic CD8+ tumor infiltrating lymphocytes (TILs) and
cancer cells, are regularly found in varying amounts in the microenvironment of
solid tumors. The purpose of this study was to find out the potential association
and combined prognostic significance of the frequency of PC, PD-1 and CD8+ TILs
in patients with intestinal cancer. METHODS: The frequency of PC, programmed cell
death protein-1 receptor (PD-1) expression and the frequency of stromal and
intraepithelial CD8+TILs were evaluated in samples of colorectal adenocarcinoma
(32 patiens) and small bowel cancer (8 patients). RESULTS: The median frequency
of PC was 0.25%. The expression of PD1 was <5% in 34 patients, 5-25% in 5
patients and 26-50% in 1 patient. The frequency of stromal CD8+ TILs was negative
in 3 patients, <25% in 26, 26-50% in 10 and >50% in 1 patient, respectively.
Intraepithelial CD8+ TILs were not detectable in 14, <25% in 24 and 26-50% in 2
patients, respectively. Statistically, the frequency of PC and PD-1 positivity
were significantly associated (p=0.004). An association between the PC frequency
and intraepithelial CD8+ TILs was of borderline statistical significance
(p=0.059). An index combining the frequency of PC and stromal CD8+ TILs, but not
the combination of frequency of PC and intraepithelial CD8+ TILs, was of
borderline prognostic significance (p=0.067). CONCLUSIONS: The present study
provides the first data on the potential association and combined prognostic
significance of frequency of PC, PD-1 and CD8+ TILs in patients with intestinal
cancer.
PMID- 29332342
TI - Study on the association between PI3K/AKT/mTOR signaling pathway gene
polymorphism and susceptibility to gastric cancer.
AB - PURPOSE: Excessive activation of PI3K/AKT/mTOR signaling pathway is one of the
most common changes in human cancers, and single nucleotide polymorphisms (SNPs)
existing in its functional region can affect the occurrence process of a variety
of cancers. This study aimed to screen out the SNPs associated with
susceptibility to gastric cancer in the PI3K/AKT/mT0R signaling pathway. METHODS:
In this case-control study, the tagging SNPs in the promoter region5'-UTR, exon
region or 3'-UTR of PIK3CA, PIK3CB, PIK3R1, PIK3R2, PIK3R3, AKT1, AKT2, AKT3 and
mTOR genes were screened out. The relationship between the genetic variation of
PI3K/AKT/mT0R signaling pathway genes and the susceptibility to gastric cancer in
Chinese Han population was investigated by this casecontrol study. RESULTS: The
results showed that the polymorphisms of the two loci, PIK3R3 rs7536272 (Additive
model: OR=1.16, 95% CI=1.01-1.35) and mTOR rs2295080 (GG vs TT: OR=0.75, 95%
CI=0.60-0.94; Additive model: OR=0.78, 95% CI=0.66- 0.93), were associated with
the risk of gastric cancer in the studied population and there was a combined
effect between the two loci (ptrend=0.005). CONCLUSIONS: In conclusion, the
polymorphisms of the two loci, PIK3R3 rs7536272 and mTOR rs2295080, on the
PI3K/AKT/mTOR signaling pathway genes are associated with genetic susceptibility
to gastric cancer in Chinese population.
PMID- 29332343
TI - Clinical relevance of telomerase polymorphism for breast cancer: A systematic
review.
AB - PURPOSE: To perform a systematic review to explore the clinical relevance of
hTERT polymorphisms for breast cancer (BC). METHODS: Twenty-nine polymorphic
regions were evaluated after comprehensive searching of 1236 articles, and
selection of 9 publications (total of 12986 cases and 16758 controls). RESULTS:
About the influence of hTERT variants in BC risk, 3 studies showed that the
variant rs2736098 was associated with increasing risk. The variants rs10069690
and rs2853676 were also described as risk factors for BC. Only one variant
rs2736100 presented as risk factor for BC. MNS16A genotype influenced the risk of
BC in an Iranian, but not in the Greek and American populations. The associations
of 5 hTERT variants with expression of hormone receptors were also evaluated in
some studies. One study showed that the variant rs10069690 was associated to the
estrogen receptor (ER)-negative and triple negative subtype, but other authors
did not find the same results. In addition, the association of rs273618 with ER
/progesterone receptor (PR)+ cases, and rs10069690, rs2735940, rs4246742 and
rs2736100 with both negative receptors were described. After data reanalyses, we
found that the variant rs2735940 and rs2736100 were associated with ER-/PR- cases
among patients with BC. Also, the variant rs2736100 was associated with ER+/PR+
cases and the variant rs2736118 was associated to ER+/PR+ and ER-/PR+ cases.
CONCLUSIONS: The associations between hTERT variants and BC risk and outcomes
could be useful since a polymorphism can be identified before the diagnosis, but
the heterogeneity of data and analyses found in different studies lead to many
controversies.
PMID- 29332344
TI - In vitro antitumor activity of guttiferone-A in human breast cancer cells is
mediated via apoptosis, mitochondrial mediated oxidative stress and reactive
oxygen species production.
AB - PURPOSE: Breast cancer is the second most frequently diagnosed cancer and is
considered as the main cause of cancer related death in females. It is estimated
that about one-third of women with breast cancer develop metastases and
eventually die of this disease. The main treatment options for breast cancer
include surgical interventions followed by chemotherapy, hormonotherapy or
radiation. However, the side effects associated with the treatment of breast
cancer negatively affects the quality of patient's life. In the present study a
plant-derived compound, guttiferone- A, was evaluated for its anticancer activity
against MCF-7 breast cancer cell line. METHODS: MTT assay was used to evaluate
the cytotoxic effects while phase contrast microscopy was used to assess the
effects of the compound on cell morphology. Effects on reactive oxygen species
(ROS) and mitochondrial membrane potential were evaluated by flow cytometric
analysis. RESULTS: It was observed that guttiferone-A reduced the cell viability
of MCF-7 cancer cells in a dose-dependent manner. The IC50 for guttiferone-A was
found to be 15 MUM against MCF-7 cells. Moreover, guttiferone-A induced the
production of high levels of ROS and caused significant reduction in the
mitochondrial membrane potential. Additionally, guttiferone-A also induced
apoptosis in MCF-7 cancer cells in a dose-dependent manner. CONCLUSION: Taken
together, we conclude that guttiferone- A is a potential anticancer molecule and
may prove to be a lead molecule in cancer drug discovery.
PMID- 29332345
TI - Correlation between miR-19a inhibition and radiosensitivity in SiHa cervical
cancer cells.
AB - PURPOSE: MicroRNAs (miRs) have been implicated in many aspects of tumor cell
development and survival, including sensitivity to radiotherapy. In particular,
miR-19a regulates the proliferation of cervical cancer cells, but its role in
radiosensitivity is not known. Here, we describe the consequence of silencing miR
19a using antisense oligonucleotides (ASO) on the radiosensitivity of human
cervical cancer SiHa cells. METHODS: Following transfection with miR-19a-ASO or
control-ASO, SiHa cells were exposed to X-rays to determine their proliferation.
RESULTS: Silencing of miR-19a significantly improved the sensitivity of SiHa
cells to radiotherapy by reducing proliferation, increasing apoptosis,
upregulating BAX, and downregulating Bcl-2. CONCLUSION: Overall, inhibiting miR
19a significantly improves the sensitivity of SiHa cells to radiotherapy, which
could lead to new methods for the treatment of cervical cancer.
PMID- 29332346
TI - Vaginal packing volume impact on dose parameters during radiography and computed
tomography based postoperative brachytherapy of cervical carcinoma.
AB - PURPOSE: To investigate the influence of the vaginal packing volume on the
registered dose parameters evaluated by radiography (2D) and computed tomography
(CT) (3D) based brachytherapy planning in cervical cancer patients treated with
postoperative radiotherapy. METHODS: The postoperative radiotherapy was performed
in 40 cervical cancer patients with increased risk for disease relapse. Both,
radiography and CT based brachytherapy planning were done in all patients.
Vaginal packing volume was evaluated by clinical target volume (CTV)uk, assessed
on CT scans and analyzed according to the registered dose parameters: doses
delivered to the organs at risk (OAR) and the defined CTV, using both planning
methods. RESULTS: CTVuk volume had statistically significant influence on CTV
coverage with the prescribed brachytherapy doses D90 (p<0.01) and D100 (p<0.01),
revealing a CTVuk cut-off value of 25.6 cm3. Dividing the patients into two
groups according to the cutoff value, we found a statistical significance in the
registered doses to the rectal wall and no significance in the bladder wall doses
between the groups. Also, a statistically significant, negative correlation was
found between CTVuk and following doses: Rmax (rho= -0.34, p<0.05), D0.1cc (rho=
0.76, p<0.01), D1cc (rho= -0.74, p<0.01) and D2cc (rho= -0.72, p<0.01), D90 (rho=
-0.80, p<0.01), D100 (rho= -0.7, p<0.01). CONCLUSION: If the brachytherapy
vaginal packing is of a large volume (more than 25.6 cm3), an asymmetric
deformation of the proximal part of the vaginal cavity might appear, leading to
inappropriate dose coverage of the CTV part of the vaginal mucosa. Also, making a
vaginal packing volume larger than 25.6 cm3 made no further reduction in the
bladder dose, but it made a statistically significant further reduction in the
rectal doses.
PMID- 29332347
TI - Genetically engineered bone marrow-derived mesenchymal stem cells co-expressing
IFN-gamma and IL-10 inhibit hepatocellular carcinoma by modulating MAPK pathway.
AB - PURPOSE: One of the major challenges in delivering cytokines for the treatment of
hepatocellular carcinoma (HCC) is the mode of delivery. This study hypothesized
that genetically engineered bone marrow derived mesenchymal stem cells (BMSCs) co
expressing IFN-gamma and IL-10 can serve as a potential therapeutic strategy in
the treatment of HCC by inhibiting cell proliferation. METHODS: Male Sprague
Dawley rats (n=5, 200-250 g) for BMSCs isolation and Nude/SCID mice (n=35,12-20g)
to develop liver cancer xenograft model were used. Mice were subcutaneously
injected HepG2 cell suspension on left flank. BMSCs were genetically engineered
with the recombinant lentiviral vectors expressing IFN-gamma and IL-10. The
experiments were performed in 5 groups (phosphate buffered saline/PBS, BMSCs,
BMSC-IFN-gamma, BMSC-IL-10 and BMSC-IFN-gamma-IL-10) and the genetically
engineered BMSCs were transplanted into HCC mice. Cell viability was measured by
MTT assay followed by the evaluation of the effect of cell-cycle regulators (p21,
p27, cyclin D1 and Rb). Protein expression of p38, ERK and JNK was assessed by
immunohistochemistry using the cell proliferation marker Ki67. RESULTS: The
combination of two cytokines (IFN-gamma and IL- 10) engineered into BMSCs
resulted in a significant reduction in HepG2 cell viability (*p<0.05 vs PBS
treated and #p<0.05 vs BMSC-treated group). Significantly increased expression of
cell cycle inhibitors p21 and p27 in parallel with reduced cyclin D1 expression
were observed. Reduced phosphorylation of Rb demonstrated the repression of G1/S
progression. BMSC-IFN-gamma-IL-10 treatment significantly reduced the tumor
growth at the end of 36 days compared to the group treated with PBS or BMSCs
alone. This effect was accompanied with the modulation of MAPK pathway with the
activation of p38 and JNK, and inactivation of ERK. CONCLUSION: The co-expression
of IFN-gamma and IL-10 in BMSCs inhibits HCC in vitro and in vivo by modulating
cell cycle regulators and MAPK pathway.
PMID- 29332348
TI - Sorafenib combined with radiofrequency ablation as treatment for patients with
hepatocellular carcinoma: a systematic review and meta-analysis.
AB - PURPOSE: To evaluate the safety and efficacy of a combination of sorafenib and
radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC).
METHODS: A systematic literature search was conducted using PubMed, Embase, the
Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology
Medicine disc (CBMdisc), WanFang Database, for all years up to January 2017.
Pooled analyses of overall survival (OS), tumor- free survival, recurrence rates
and adverse events were performed. RESULTS: IA total of 7 case control studies
consisting of 1765 HCC patients were selected and included in this metaanalysis.
Patients treated with sorafenib-RFA and sorafenib alone, RFA alone and surgery
had no significant differences in 1-year OS (p=0.310), 2-year OS (p=0.262), 3
year OS (p=0.179), 4-year OS (p=0.238) and 5-year OS (p=0.933); 1-year recurrence
rate (p=0.653), 2-year recurrence rate (p=0.416), 3-year recurrence rate
(p=0.304), and 5-year recurrence rate (p=0.807); 1-year tumor-free survival rate
(p=0.943), 3-year tumor-free survival rate (p=0.825), 5-year tumor-free survival
rate (p=0.893) and overall adverse events (p=0.097). CONCLUSION: RFA-sorafenib
combination may not be a better approach for patients with HCC. More well
designed randomized clinical trials (RCTs) should be performed before we finally
arrive at a rational comprehension about the therapeutic value of the discussed
options.
PMID- 29332349
TI - Characteristics and clinical significance of recurrent laryngeal nerve lymph node
metastasis in esophageal squamous cell carcinoma.
AB - PURPOSE: The recurrent laryngeal nerve lymph nodes (RLN LNs) are among the most
common metastatic sites in esophageal cancer, and the dissection of these lymph
nodes (LNs) is considered beneficial. The purpose of this study was to evaluate
the characteristics of RLN LN metastases from esophageal squamous cell carcinoma,
and the effects of these metastases on the prognosis of patients. In addition, we
aimed to determine the reasonable range of dissection of regional LNs. METHODS:
The clinical data from 348 patients who underwent resection for esophageal
carcinoma were retrospectively analyzed. RESULTS: Recurrent laryngeal nerve palsy
occurred in 37.6% of the patients. In a subgroup of patients with lower
esophageal tumors, cervical LN metastases were significantly more common in
patients with positive rather than negative RLN LNs. The primary tumor site,
tumor differentiation, and tumor invasion depth were factors that significantly
influenced RLN LN metastasis. Multivariate analysis revealed that RLN LN
metastasis was a significant factor associated with overall survival (OS) and
disease-free survival (DFS) (p<0.001). CONCLUSION: Metastasis to RLN LNs is a
reliable indicator of cervical LN metastasis in middle/lower thoracic esophageal
cancer. RLN LN metastasis may act as a prognostic indicator for patients with
esophageal squamous cell carcinoma.
PMID- 29332350
TI - Short- and long-term outcomes of minimally invasive esophagectomy in elderly
patients with esophageal squamous cell carcinoma.
AB - PURPOSE: In recent years, there has been an increase in the number of elderly
patients undergoing surgery for esophageal squamous cell carcinoma (ESCC).
However, there are few studies on short- and long-term outcomes of minimally
invasive esophagectomy (MIE) in such patients. The purpose of this study was to
report both short- and long-term outcomes of MIE in elderly patients with ESCC.
METHODS: A total of 273 patients with ESCC underwent MIE at our hospital from
January 2010 to December 2016. Patients were divided into elderly (>=70 years)
and nonelderly (<70 years) groups based on age at the time of surgery. Groups
were compared with regard to general preoperative data, intraoperative data,
postoperative 30-day complications and their severity, pathological result,
recurrence, overall survival (OS), and disease-free survival (DFS) rates.
RESULTS: The elderly group was characterized by higher Charlson Comorbidity Index
>2 and American Society of Anesthesiologists (ASA) grade. Comparisons of other
general preoperative data showed no significant differences. In addition, there
were no significant differences in short-term outcomes except for postoperative
30-day complication rate. Although 30-day postoperative complication rate was
higher in the elderly group compared with the nonelderly group, the incidence of
major complications was similar between groups. Cancer recurrence, 5-year OS, and
5-year DFS rates also were similar between groups. CONCLUSION: Although elderly
patients with ESCC had higher Charlson Comorbidity Index and ASA grade, they
could achieve short- and long-term outcomes of MIE similar to those of nonelderly
patients.
PMID- 29332351
TI - Cytoreductive surgery and hyperthermic intraperitenoal chemotherapy (HIPEC) for
colorectal and appendiceal carcinomas with peritoneal carcinomatosis.
AB - PURPOSE: Cytoreductive surgery combined with intraperitoneal chemotherapy has
been established as the standard treatment for selected patients with peritoneal
malignancy. The purpose of the study was the presentation of the 10- year
experience with cytoreductive surgery and intraperitoneal chemotherapy in
patients with peritoneal carcinomatosis of colorectal and appendiceal origin.
METHODS: Clinical and histopathological variables were retrospectively reviewed
in a prospectively maintained database. All patients underwent cytoreductive
surgery with the purpose of complete or near-complete cytoreduction. The
variables were correlated to survival, and recurrences. Morbidity and hospital
mortality were recorded. RESULTS: From 2006-2016 100 patients underwent
cytoreductive surgery for colorectal and appendiceal carcinomas with peritoneal
carcinomatosis. The hospital mortality and morbidity were 2% and 43%
respectively. Completeness of cytoreduction (CC) 0 surgery was possible in 51% of
the patients. The median and 10-year survival were 13 months and 23%
respectively. The completeness of cytoreduction, performance status and the lymph
node status were identified as prognostic indicators of survival. The recurrence
rate was 55%. The completeness of cytoreduction, the lymph node status, and the
use of postoperative adjuvant systemic chemotherapy were identified as prognostic
variables of recurrence. CONCLUSION: Nearly half of the patients with peritoneal
carcinomatosis of colorectal and appendiceal origin may undergo complete
cytoreduction and nearly half of them may enjoy long-term survival.
PMID- 29332352
TI - Puerarin leads to K562 cell apoptosis of chronic myelogenous leukemia via
induction of autophagy.
AB - PURPOSE: To study the effects of puerarin on the viability, apoptosis and
autophagy of K562 cells of chronic myelogenous leukemia (CML), and to provide a
basis for the study on antitumor mechanism of puerarin. METHODS: K562 cells of
human CML were taken as the study material and puerarin was applied in different
concentrations. The effect of puerarin on cell viability was detected via
cholecystokinin-8 (CCK8) and lactate dehydrogenase (LDH). Flow cytometry and
western blot (WB) were used to detect cell apoptosis, while Cyto-ID and WB were
used to detect the cell autophagy level. RESULTS: Puerarin inhibited the K562
cell viability and increased cell apoptosis and autophagy in a dose-dependent
manner. After 3-methyladenine (3-MA) autophagy inhibitor was used, puerarin's
induction of cell autophagy was inhibited, and its apoptosis induction was also
inhibited. CONCLUSIONS: Puerarin increases the cell apoptosis through induction
of autophagic apoptosis of K562 cells.
PMID- 29332353
TI - Aesculetin (6,7-dihydroxycoumarin) exhibits potent and selective antitumor
activity in human acute myeloid leukemia cells (THP-1) via induction of
mitochondrial mediated apoptosis and cancer cell migration inhibition.
AB - PURPOSE: The main target of the present research was to examine the antitumor
properties of aesculetin in human acute myeloid leukemia cancer cells (THP-1) and
peripheral blood mono-nucleated cells (PBMCs) (used as normal cell line model)
along with the determination of its effects on induction of apoptosis, inhibition
of cancer cell migration and changes in Bcl-2/Bax protein expressions. METHODS:
MTT colorimetric bioassay was performed to study the impact of this natural
compound on cytotoxicity of both cell types. Moreover, transmission electron
microscopy (TEM), inverted phase contrast and fluorescence microscopic techniques
were used to study the effects on cell morphology and cellular ultrastructural
details connected with apoptosis. The effects of aesculetin on Bcl-2/Bax protein
expressions were assessed by Western blot method. RESULTS: Selective and dose
dependent antiproliferative activity of aesculetin in human acute myeloid
leukemia cancer cells was observed. However, the compound did not induce
significant cell growth inhibition of PBMCs, which were used as normal cell
controls. Fluorescence and inverted phase contrast microscopic techniques
revealed that aesculetin led to morphological changes suggestive of apoptosis
(cell shrinkage, chromatin abridgment and membrane blebbing). TEM analysis showed
that aesculetin led to fragmented plasma membrane along with appearance of
spherical projections (apoptotic bodies). The wound scratch widened after
aesculetin treatment, indicating that aesculetin exhibits anticancer effects by
suppressing the cancer cell migration. Aesculetin led to significant and dose
dependent reduction in the Bcl-2 expression while the expression of Bax was
significantly enhanced resulting in overall reduction of Bcl-2/Bax ratio.
CONCLUSION: The results of the present work revealed that aesculetin exhibits
selective anticancer effects in THP-1 human leukemia cells without causing much
cytotoxicity in PBMCs. It also led to significant apoptosis induction, inhibition
of cancer cell migration and decrease in Blc-2/Bax ratio.
PMID- 29332354
TI - Inhibition of telomerase potentiates enzalutamide efficiency of androgen
sensitive human prostate cancer cells.
AB - PURPOSE: Androgen deprivation therapy (ADT) is one of the main strategies to
treat prostate cancer (PCa) at various stages of its development. Androgen
receptor (AR) antagonists such as enzalutamide are mainstay treatments for
castration-sensitive prostate cancer. Though, a majority of patients initially
respond to ADT, most will eventually progress to castrate-resistant, due to the
development of different mutations on the AR. PCa cells express high telomerase
activity, and there is a correlation between the total activity of telomerase and
the Gleason score. Therefore, we hypothesized that the combination of
enzalutamide plus a telomerase inhibitor could be more effective than
enzalutamide alone in decreasing cell survival. METHODS: In this study MTT test,
RT-qPCR and imagebased cytometry were used to investigate cell viability,
apoptosis and cell cycle progression of androgen-responsive human prostate cancer
LNCaP cells. The cells were treated with 5 MUM enzalutamide and 40 MUM telomerase
inhibitor BIBR 1532, or with their combinations for 72 hrs. RESULTS: Enzalutamide
and BIBR 1532 alone inhibited cell proliferation in a dose-dependent manner. The
combinations of the two agents could synergistically induce apoptotic and
necrotic cell death. Either inhibition of telomerase by BIBR 1532 or AR blockages
by enzalutamide decreased prostate-specific antigen (PSA) and the catalytic
component of telomerase, hTERT, expression. CONCLUSION: These results suggest
that telomerase inhibition therapy may contribute to the efficacy of enzalutamide
in the androgen-sensitive PCa model.
PMID- 29332355
TI - Antitumor activity of 4-O-Methylhonokiol in human oral cancer cells is mediated
via ROS generation, disruption of mitochondrial potential, cell cycle arrest and
modulation of Bcl-2/Bax proteins.
AB - PURPOSE: The plant-derived natural product 4-O-methylhonokiol (MH) has been
reported to possess tremendous pharmacological potential ranging from
neuroprotection to anticancer activity. However, the anticancer activity of MH in
oral squamous cell carcinoma (OSCC) cells has not been evaluated. In the present
study, MH was evaluated for its anticancer activity against OSSC PE/CA-PJ41 cells
and the possible underlying mechanism was determined. METHODS: Cell cytotoxicity
was evaluated by colorimetrybased MTT assay while the effects on cell cycle phase
distribution were assessed by flow cytometry. Effects of MH on reactive oxygen
species (ROS) production and mitochondrial membrane potential (MMP) were
evaluated by flow cytometry. Western blot assay was finally utilized to study the
effects of MH on key cancer and apoptosis-linked proteins including Bax and Bcl
2. RESULTS: MH induced cytotoxicity in OSCC PE/CA-PJ41 cells with an observed
IC50 of 1.25 MUM. It also caused significant increase in the production of ROS
and disrupted the MMP in a dose-dependent manner. The reduction in MMP favored
mitochondrial apoptotic pathway which was further confirmed by determining the
expression of Bax and Bcl-2. It was observed that MH downregulated the expression
of Bax and upregulated the expression of MMP, ultimately leading to apoptosis of
OSSC PE/CA-PJ41 cells. Additionally, MH also caused G2/M cell cycle arrest in a
dose-dependent manner. CONCLUSION: Taken together, our results indicate that 4
Omethylhonokiol may prove a potential natural anticancer molecule against human
oral carcinoma cells.
PMID- 29332356
TI - beta-Aescin shows potent antiproliferative activity in osteosarcoma cells by
inducing autophagy, ROS generation and mitochondrial membrane potential loss.
AB - PURPOSE: Osteosarcoma is one of the frequent bone tumor affecting mainly children
and is associated with considerable mortality. The limited availability of
anticancer drugs and less efficacious treatment options have led to poor survival
rates of patients with osteosarcoma. Therefore, there is need to look for more
viable treatment options and against this backdrop, natural products may prove
handy. Therefore the aim of the present study was to evaluate the anticancer
activity of a natural product of plant origin, beta-aescin, against U2OS human
osteosarcoma cells. METHODS: U205 human osteosarcoma cell line was used in this
study. Antiproliferative activity was determined by MTT assay. Reactive oxygen
species (ROS) and mitochondrial membrane potential (MMP) were evaluated by flow
cytometry. Autophagy was detected by monodansylcadaverine (MDC) staining and
immunofluorescence. Protein expression was examined by western blotting. RESULTS:
The results indicated that beta-aescin showed significant anticancer activity
against U2OS human osteosarcoma cells and exhibited an IC50 of 40 MUM. beta
aescin treatment caused significant increase in ROS and decrease in the MMP. The
anticancer effect of beta-aescin was found to be due mainly to autophagic cell
death as evidenced from MDC staining and immunofluorescence. Moreover, beta
aescin caused significant increase in the expression levels of LC3- II protein in
U2OS osteosarcoma cells in a time and dosedependent manner. CONCLUSION: Taken
together we propose that beta-aescin may prove a lead molecule in the management
of osteosarcoma and deserves further research efforts.
PMID- 29332357
TI - Management of B3 lesions of the breast: implementations of current
recommendations in clinical practice.
AB - PURPOSE: Stereotactic needle breast biopsy and vacuum assisted breast biopsy have
replaced wide local excision in the last decades. B3 lesions of the breast
represent a particular subgroup which is difficult to manage. The purpose of the
present study was to present our experience with this specific type of lesions
and to examine the conformity of Princess Margaret Hospital with current
recommendations. METHODS: We retrospectively searched for patients that attended
the Breast Clinic of Princess Alexandra Hospital during the period 2012-2015, and
were diagnosed with B3 lesions during stereotactic needle core biopsy. RESULTS:
In total 24 patients with B3 lesions were identified. Among them 6 women had
synchronous malignant lesions and were excluded from our study. From the
remaining, 8 patients presented with a single B3 lesion and 10 with multiple B3
lesions. Twelve of our patients underwent stereotactic vacuum-assisted biopsy
(VAB). Ten patients underwent only core biopsy, 8 underwent only VAB biopsy and 3
lesions were investigated with both core biopsy and VAB. CONCLUSIONS: The
findings of our study support the applicability of the current recommendations
for the surgical management of B3 breast lesions. Core needle biopsies and VAB
are equally efficacious with wide local excision for the differential diagnosis
of lesions of uncertain malignant potential, thus limiting the necessity of open
surgery.
PMID- 29332358
TI - A study on basic demographic and disease characteristics of cancer-diagnosed
Syrian refugees treated in the border city of Turkey, Sanliurfa; a hospital-based
retrospective case series study.
AB - PURPOSE: Turkey hosts around 3 million Syrian refugees which is more than any
other country in the world. Along with some other adaptation issues like
cultural, language, and economic difficulties, significant problems in managing
medical problems, chronic diseases like cancer in particular, have to be fixed.
However, there are few studies which explore main patient and clinicopathological
characteristics in Syrian refugees with cancer. The purpose of this study was to
highlight the aforementioned characteristics along with management issues after
cancer diagnosis of these patients. METHODS: This study was designed as a
hospital-based retrospective observational case-series study of 134 Syrian
refugees cancer patients between 2015 and 2017. RESULTS: The patient median age
was 47.5 years (range 18- 80). Out of the 134, 102 (76.1%) were female. The most
common cancer types were breast (n=57, 42.5%) and gynecological cancers (n=14,
10.4%). The majority of patients were diagnosed at advanced stage (n=60, 44.8%).
There were 91 (67.9%) and 43 (32.1%) patients admitted to our center from refugee
camps and staying in a house, respectively. The median follow-up was 14 months
(range 1-111) and 11 (8.2%) patients died. One and two-year survival rate of the
whole group were 93% and 86%, respectively. There were 12 (9%) patients with
grade 3-4 hematological and non-hematological toxicities. Neutropenia was the
most common grade 3-4 toxicity (n=8, 6%). The patients staying in refugee camp (n
91) or in a house (n=43) finished all planned cycles of chemotherapy with a rate
of 71% (n=65) and 79% (n=34), respectively. Statistical analysis failed to show
significant relationship between the staying site (either camp or house),
chemotherapy compliance rate, grade 3-4 toxicities with p=0.347 and p=0.09,
respectively. CONCLUSION: Our results revealed that breast cancer and
gynecological cancers were the most common cancer types which are good candidates
for cancer screening. Unfortunately, the majority of patients had cancer
diagnosed at advanced stage. However, after diagnosis they could reach all health
facilities including surgical operation, radiotherapy, and systemic chemotherapy
similar to Turkish cancer patients. Therefore, our results suggested that major
problem for the Syrian refugees adapting them into national screening program
which may resulted that cancer diagnosis at earlier stage with high cure rate.
PMID- 29332359
TI - Novel molecular and metabolic aspects in osteosarcoma.
AB - Osteosarcoma (OS) is the most frequent bone-forming malignancy in children and
adolescents. Concerning its molecular landscape, there is no a direct
relationship with a specific gene, but a combination of genetic events. A broad
spectrum of activated oncogenes and downregulated suppressor genes has been
already explored and considered crucial for its progressive pathogenesis.
Mechanisms of gene deregulation include amplifications, point mutations, allelic
losses and also epigenetic abnormalities such as aberrant promoter methylation.
Although a significant progress in understanding the molecular nature of the OS
has been achieved, its aggressive phenotype - characterized by high metastatic
potential - remains unexplored. Novel targeted therapeutic strategies include
monoclonal antibodies (mABs) and also tyrosine-kinase inhibitors (TKIs).
Additionally, sophisticated and innovative diagnostic techniques, such as 18
fluorodeoxyglucose positron emission tomography plus CT (18F-FDG/PET/CT), provide
critical data regarding its biological behavior. In the current paper, we present
novel molecular and metabolic advances by analyzing OS genetic profile and
biochemical microenvironment.
PMID- 29332360
TI - From Fungus haematodes to Retinoblastoma.
AB - Retinoblastoma is probably the only disease which received 40 different names
until its official terminology which was adopted by the medical community in
1926. The official record of retinoblastoma was reported in 1597 by Petrus Pawius
(ca. 1564-1617). The development of pathology during the 19th century gave to
opportunity to clarify the histological characteristics of the disease. Although
in the past retinoblastoma was considered a fatal disease, nowadays with modern
treatment the prognosis is better.
PMID- 29332361
TI - Bisphosphonate-associated orbital inflammation: is it class-specific side effect?
PMID- 29332362
TI - Association of non-Hodgkin's lymphoma with advanced endometriosis.
PMID- 29332363
TI - A brain ependymoma with psychiatric manifestation.
PMID- 29332364
TI - Medical errors done with good intention, according to the believes of the time in
the past: oncology should be evidence-based nowadays.
PMID- 29332365
TI - Positional errors in linear accelerator based frameless cranial stereotaxy: A
note of caution.
PMID- 29332366
TI - Molecular landscape in laryngeal chondrosarcoma.
PMID- 29332367
TI - The role of tyrosine kinase inhibitors (TKIs) as adjuvant treatment for renal
cancer. Where do we stand today?
PMID- 29332368
TI - "Pearl oyster": a new ultrasonographic sign of the regressed testicular tumor.
PMID- 29332369
TI - Preliminary testing of anthracycline-induced cardiotoxicity in children.
PMID- 29332370
TI - Hallmarks in the evolution of gynaecological cancer surgery: the famous pioneers
in children.
AB - At the beginning of the 19th century, gynaecological cancer, mainly cancer of the
uterus and cervix was a dreadful, incurable affection. However, the
popularization of the three fundamentals in surgery, anesthesia, asepsis and
haemostasis, ushered the golden age of operative gynaecology. During that period
distinguished surgeons/gynaecologists such as Friedrich Benjamin Osiander (1759
1822), Elias von Siebold (1775-1828) and Joseph-Claude-Anthelme Recamier (1774
1852) contributed to the development of the operative techniques, providing a
therapeutic solution in gynaecological cancer.
PMID- 29332372
TI - Measurement and modeling of indoor radon concentrations in residential buildings.
AB - Radon, the primary constituent of natural radiation, is the second leading
environmental cause of lung cancer after smoking. To confirm a relationship
between indoor radon exposure and lung cancer, estimating cumulative levels of
exposure to indoor radon for an individual or population is necessary. This study
sought to develop a model for estimate indoor radon concentrations in Korea.
Especially, our model and method may have wider application to other residences,
not to specific site, and can be used in situations where actual measurements for
input variables are lacking. In order to develop a model, indoor radon
concentrations were measured at 196 ground floor residences using passive alpha
track detectors between January and April 2016. The arithmetic mean (AM) and
geometric mean (GM) means of indoor radon concentrations were 117.86+/-72.03 and
95.13+/-2.02 Bq/m3, respectively. Questionnaires were administered to assess the
characteristics of each residence, the environment around the measuring
equipment, and lifestyles of the residents. Also, national data on indoor radon
concentrations at 7643 detached houses for 2011-2014 were reviewed to determine
radon concentrations in the soil, and meteorological data on temperature and wind
speed were utilized to approximate ventilation rates. The estimated ventilation
rates and radon exhalation rates from the soil varied from 0.18 to 0.98/hr (AM,
0.59+/-0.17/hr) and 326.33 to 1392.77 Bq/m2/hr (AM, 777.45+/-257.39; GM, 735.67+/
1.40 Bq/m2/hr), respectively. With these results, the developed model was applied
to estimate indoor radon concentrations for 157 residences (80% of all 196
residences), which were randomly sampled. The results were in better agreement
for Gyeonggi and Seoul than for other regions of Korea. Overall, the actual and
estimated radon concentrations were in better agreement, except for a few low
concentration residences.
PMID- 29332373
TI - Use of adverse outcome pathways in chemical toxicity testing: potential
advantages and limitations.
AB - Amid revolutionary changes in toxicity assessment brought about by increasing
regulation of chemicals, adverse outcome pathways (AOPs) have emerged as a useful
framework to assess adverse effect of chemicals using molecular level effect,
which aid in setting environmental regulation policies. AOPs are biological maps
that describe mechanisms linking molecular initiating event to adverse outcomes
(AOs) at an individual level. Each AOP consists of a molecular initiating event,
key events, and an AO. AOPs use molecular markers to predict endpoints currently
used in risk assessment, promote alternatives to animal model-based test methods,
and provide scientific explanations for the effects of chemical exposures.
Moreover, AOPs enhance certainty in interpreting existing and new information.
The application of AOPs in chemical toxicity testing will help shift the existing
paradigm of chemical management based on apical endpoints toward active
application of in silico and in vitro data.
PMID- 29332375
TI - Recurrent aphtous stomatitis.
AB - Recurrent aphtous stomatitis (recurrent aphtous ulcers, canker sores) is the most
common ulcerative disease of the oral mucosa. In this paper we presented the main
clinical features, epidemiologic data, etiopathogenetic factors and clinical
management, based on the current medical literature reports.
PMID- 29332374
TI - Transcatheter aortic valve replacement in bicuspid aortic valve stenosis: where
do we stand?
AB - Bicuspid aortic valve is the most common congenital cardiac defect in adults, and
symptom typically develops in adulthood. In the majority of cases, bicuspid
aortic valve disease progress with ages and surgical aortic valve replacement is
performed with excellent operative outcomes. However, with the relatively slow
progression of disease, surgical aortic valve replacement is required in elderly
patients but the surgical risk often deemed extremely high due to old age and
multiple comorbidities. Transcatheter aortic valve replacement (TAVR) has evolved
from a novel technology to an established therapy for intermediate- and high-risk
patients with symptomatic severe aortic valve stenosis (AS). Numerous studies
have demonstrated the safety and efficacy of TAVR, and more than 250,000 patients
have been treated with this technology. Although randomized trials have
established TAVR as the standard treatment, these trials excluded congenital
bicuspid AS due to its unique morphological features. Nevertheless, the growing
experience, accumulated knowledge, and advancements of new technology lead to the
expand use of TAVR to other pathologies or other populations such as bicuspid AS.
With integration of imaging multimodalities (computed tomography and
echocardiography), the diagnosis and classification of bicuspid aortic valve has
been changing. Due to unfavorable anatomic features of bicuspid AS, the outcomes
of TAVR in bicuspid AS was suboptimal, particularly when using the first
generation transcatheter valves. However, the newer-generation transcatheter
valves significantly improved the outcomes of TAVR in bicuspid AS. Nonetheless,
several issues still remain to be resolved. Given longer life expectancy in
patients with bicuspid AS undergoing TAVR, durability of transcatheter valves is
concerned. In addition, patients with bicuspid aortic valves often have
concomitant dilatation of proximal part of ascending aorta (aortopathy), but
limited data exist about the clinical prognosis of bicuspid aortic valve with
concomitant aortopathy in elderly patients. Considering the expanding indication
of TAVR to lower surgical risk and younger population, these issues should be
evaluated in future studies.
PMID- 29332378
TI - Role of psoriasis on subclinical cardiovascular disease.
PMID- 29332379
TI - Correlation among atherosclerosis, cardiac and respiratory function in subjects
with cystic fibrosis.
PMID- 29332377
TI - Comparisons of three different doses of alirocumab application in patients with
hypercholesterolemia: a meta-analysis.
AB - INTRODUCTION: Low high-density lipoprotein cholesterol (HDL-C) and high low
density lipoprotein cholesterol (LDL-C) levels are associated with incidence of
cardiovascular disease (CVD). Alirocumab has been considered as an efficacious,
safe and promising therapeutic modality for hypercholesterolemia. The purpose of
this study is to compare the differences of the three different doses of
alirocumab in patients with hypercholesterolemia. EVIDENCE ACQUISITION:
Randomized controlled trials were identified from PubMed, EMBASE, PMC and
Cochrane-library databases. The inter-comparison of different doses were
performed by subgroups analysis. Meta-analyses were performed by the Review
Manager 5.3 and STATA 13.0 software. EVIDENCE SYNTHESIS: A total of nine studies
involving 3870 patients were included in this meta-analysis. Alirocumab
administered at 75-150 mg every 2 weeks (Q2W) resulted in a greater percent
change from baseline in LDL-C concentrations (MD, -55.17; 95% CI: -64.35 to
45.99; P<0.05), and HDL-C levels (MD, 7.70; 95% CI 5.94 to 9.46; P<0.05) than
other two doses (300 mg every 4 weeks [Q4W], 150 mg every 2 weeks [Q2W]). There
was no difference in achieving the treatment goal of LDL-C (<=1.8 mmol/L), in
other serum lipid parameters (total cholesterol [TC], triglyceride [TG]), and in
the incidence of adverse events. CONCLUSIONS: The results demonstrate that
alirocumab at a dose of 75-150 mg Q2W should be preferred in patients with
hypercholesterolemia.
PMID- 29332376
TI - New and emerging treatments for metastatic Merkel cell carcinoma.
PMID- 29332380
TI - Solvent Modulation of Aromatic Substituent Effects in Molecular Balances
Controlled by CH-pi Interactions.
AB - CH-pi aromatic interactions are ubiquitous in nature and are capable of
regulating important chemical and biochemical processes. Solvation and aromatic
substituent effects are known to perturb the CH-pi aromatic interactions.
However, the nature by which the two factors influence one another is relatively
unexplored. Here we demonstrate experimentally that there is a quantitative
correlation between substituent effects in CH-pi interactions and the hydrogen
bond acceptor constants of the solvating molecule. The CH-pi interaction energies
were measured by the conformational study of a series of aryl-substituted
molecular balances in which the conformational preferences depended on the
relative strengths of the methyl and aryl CH-pi interactions in the folded and
unfolded states, respectively. Due to the favorable methyl-aromatic interactions,
the balances were found to exist predominantly in the folded state. The observed
substituent effect in the conformational preferences of the balances was
controlled by the explicit solvation/desolvation of the aryl proton. The
interpretation of the conformational free energy as a function of substituents
and solvation using Hunter's solvation model revealed that a linear relationship
exists between the sensitivity of aromatic substituent effects (i.e., the rho
values derived from Hammett plots) and the hydrogen-bond acceptor propensity
(betas) of the solvent molecule: rho = 0.06betas - 0.04.
PMID- 29332381
TI - Significant Role of Mg Stoichiometry in Designing High Thermoelectric Performance
for Mg3(Sb,Bi)2-Based n-Type Zintls.
AB - Complex structures with versatile chemistry provide considerable chemical
tunability of the transport properties. Good thermoelectric materials are
generally extrinsically doped semiconductors with optimal carrier concentrations,
while charged intrinsic defects (e.g., vacancies, interstitials) can also adjust
the carriers, even in the compounds with no apparent deviation from a
stoichiometric nominal composition. Here we report that in Zintl compounds
Mg3+xSb1.5Bi0.5, the carrier concentration can be tuned from p-type to n-type by
simply altering the initial Mg concentration. The spherical-aberration-corrected
(CS-corrected) high-angle annular dark field scanning transmission electron
microscopy (HAADF-STEM) and energy-dispersive X-ray spectroscopy (EDX) mapping
analysis show that the excess Mg would form a separate Mg-rich phase after Mg
vacancies have been essentially compensated. Additionally, a slight Te doping at
Bi site on Mg3.025Sb1.5Bi0.5 has enabled good n-type thermoelectric properties,
which is comparable to the Te-doped Mg-rich sample. The actual final composition
of Mg3.025Sb1.5Bi0.5 analyzed by EPMA is also close to the stoichiometry
Mg3Sb1.5Bi0.5, answering the open question whether excess Mg is prerequisite to
realize exceptionally high n-type thermoelectric performance by different sample
preparation methods. The motivation for this work is first to understand the
important role of vacancy and then to guide for discovering more promising n-type
Zintl thermoelectric materials.
PMID- 29332382
TI - Cu2I2Se6: A Metal-Inorganic Framework Wide-Bandgap Semiconductor for Photon
Detection at Room Temperature.
AB - Cu2I2Se6 is a new wide-bandgap semiconductor with high stability and great
potential toward hard radiation and photon detection. Cu2I2Se6 crystallizes in
the rhombohedral R3m space group with a density of d = 5.287 g.cm-3 and a wide
bandgap Eg of 1.95 eV. First-principles electronic band structure calculations at
the density functional theory level indicate an indirect bandgap and a low
electron effective mass me* of 0.32. The congruently melting compound was grown
in centimeter-size Cu2I2Se6 single crystals using a vertical Bridgman method. A
high electric resistivity of ~1012 Omega.cm is readily achieved, and detectors
made of Cu2I2Se6 single crystals demonstrate high photosensitivity to Ag Kalpha X
rays (22.4 keV) and show spectroscopic performance with energy resolutions under
241Am alpha-particles (5.5 MeV) radiation. The electron mobility is measured by a
time-of-flight technique to be ~46 cm2.V-1.s-1. This value is comparable to that
of one of the leading gamma-ray detector materials, TlBr, and is a factor of 30
higher than mobility values obtained for amorphous Se for X-ray detection.
PMID- 29332383
TI - Developing Pantetheinase-Resistant Pantothenamide Antibacterials: Structural
Modification Impacts on PanK Interaction and Mode of Action.
AB - Pantothenamides (PanAms) are analogues of pantothenate, the biosynthetic
precursor of coenzyme A (CoA), and show potent antimicrobial activity against
several bacteria and the malaria parasite in vitro. However, pantetheinase
enzymes that normally degrade pantetheine in human serum also act on the PanAms,
thereby reducing their potency. In this study, we designed analogues of the known
antibacterial PanAm N-heptylpantothenamide (N7-Pan) to be resistant to
pantetheinase by using three complementary structural modification strategies. We
show that, while two of these are effective in imparting resistance, the
introduced modifications have an impact on the analogues' interaction with
pantothenate kinase (PanK, the first CoA biosynthetic enzyme), which acts as a
metabolic activator and/or target of the PanAms. This, in turn, directly affects
their mode of action. Importantly, we discover that the phosphorylated version of
N7-Pan shows pantetheinase resistance and antistaphylococcal activity, providing
a lead for future studies in the ongoing search of PanAm analogues that show in
vivo efficacy.
PMID- 29332384
TI - Structure of Lipid Nanoparticles Containing siRNA or mRNA by Dynamic Nuclear
Polarization-Enhanced NMR Spectroscopy.
AB - Here, we show how dynamic nuclear polarization (DNP) NMR spectroscopy experiments
permit the atomic level structural characterization of loaded and empty lipid
nanoparticles (LNPs). The LNPs used here were synthesized by the microfluidic
mixing technique and are composed of ionizable cationic lipid (DLin-MC3-DMA), a
phospholipid (distearoylphosphatidylcholine, DSPC), cholesterol, and
poly(ethylene glycol) (PEG) (dimyristoyl phosphatidyl ethanolamine (DMPE)-PEG
2000), as well as encapsulated cargoes that are either phosphorothioated siRNA
(50 or 100%) or mRNA. We show that LNPs form physically stable complexes with
bioactive drug siRNA for a period of 94 days. Relayed DNP experiments are
performed to study 1H-1H spin diffusion and to determine the spatial location of
the various components of the LNP by studying the average enhancement factors as
a function of polarization time. We observe a striking feature of LNPs in the
presence and in the absence of encapsulating siRNA or mRNA by comparing our
experimental results to numerical spin-diffusion modeling. We observe that LNPs
form a layered structure, and we detect that DSPC and DMPE-PEG 2000 lipids form a
surface rich layer in the presence (or absence) of the cargoes and that the
cholesterol and ionizable cationic lipid are embedded in the core. Furthermore,
relayed DNP 31P solid-state NMR experiments allow the location of the cargo
encapsulated in the LNPs to be determined. On the basis of the results, we
propose a new structural model for the LNPs that features a homogeneous core with
a tendency for layering of DSPC and DMPE-PEG at the surface.
PMID- 29332385
TI - Highly Sensitive Ratiometric Self-Assembled Micellar Nanoprobe for Nitroxyl and
Its Application In Vivo.
AB - Nitroxyl (HNO) is a derivative of nitric oxide (NO) that plays an essential role
in various biological and pharmacological events. Until now, the in situ trapping
and specific detection of HNO in living samples is still challenging. In this
project, we fabricated a novel BODIPY-based micellar nanoprobe for monitoring
nitroxyl in vitro and in vivo in ratiometric mode in aqueous solution. The probe
(P-BODIPY-N) contains an asymmetrical BODIPY dye for fluorescent signaling and a
diphenylphosphinobenzoyl as the trigger moiety; then we encapsulated P-BODIPY-N
into the hydrophobic interior of an amphiphilic copolymer (mPEG-DSPE) and
prepared a novel BODIPY-based micellar nanoprobe: NP-BODIPY-N. As far as we know,
this probe is the first reported ratiometric fluorescent nanoprobe for HNO, which
exhibits ultrasensitivity, high selectivity, and good biocompatibility. Above
all, this nanoprobe shows favorable cellular uptaken and was successfully used to
detect intracellular HNO released by Angeli's salt in living cells and zebrafish
larvae. These results indicate that our newly designed nanoprobe will provide a
promising tool for the studies of HNO in living system.
PMID- 29332386
TI - Multiple yet Controllable Photoswitching in a Single AIEgen System.
AB - Seeking new methods to obtain elaborate artificial on-demand photoswitching with
multiple functionalities remains challenging. Most of the systems reported so far
possess only one specific function and their nonemissive nature in the aggregated
state inevitably limit their applications. Herein, a tailored cyanostilbene-based
molecule with aggregation-induced emission characteristic was synthesized and was
found to exhibit efficient, multiple and controllable photoresponsive behaviors
under different conditions. Specifically, three different reactions were
involved: (i) reversible Z/E isomerization under room light and thermal treatment
in CH3CN, (ii) UV-induced photocyclization with a concomitant dramatic
fluorescence enhancement, and (iii) regio- and stereoselective photodimerization
in aqueous medium with microcrystal formation. Experimental and theoretical
analyses gave visible insights and detailed mechanisms of the photoreaction
processes. Fluorescent 2D photopattern with enhanced signal-to-background ratio
was fabricated based on the controllable "turn-on" and "turn-off" photobehaviors
in different states. The present study thus paves an easy yet efficient way to
construct smart multiphotochromes for unique applications.
PMID- 29332388
TI - Immersion and Contact Efflorescence Induced by Mineral Dust Particles.
AB - The phase state of inorganic salt aerosols impacts their properties, including
the ability to undergo hygroscopic growth, catalyze heterogeneous reactions, and
act as cloud condensation nuclei. Here, we report the first observation of
contact efflorescence by mineral dust aerosol. The efflorescence of aqueous
ammonium sulfate ((NH4)2SO4) and sodium chloride (NaCl) droplets by contact with
three types of mineral dust particles (illite, montmorillonite, and NX illite),
were examined using an optical levitation chamber. Immersion mode efflorescence
was also studied for comparison. We find that in the presence of mineral dust
particles, crystallization occurred at a higher relative humidity (RH) when
compared to the homogeneous phase transition. Additionally, crystallization by
contact mode efflorescence occurred at a higher RH than the corresponding
immersion mode. Crystallization efficiencies in the contact mode exhibited an ion
specific trend consistent with the Hoffmeister series. Estimates for lifetimes of
a salt droplet to collide with dust particles suggests that collisions between
the two aerosol types are likely to occur before the salt aerosol is removed by
other atmospheric processes. Such collisions could then lead to the
crystallization of salt droplets that would otherwise have remained liquid,
changing the overall impact that salt aerosols have on atmospheric chemistry and
climate.
PMID- 29332389
TI - Direct Catalytic Asymmetric Mannich-Type Reaction en Route to alpha-Hydroxy-beta
amino Acid Derivatives.
AB - A direct catalytic Mannich-type reaction of alpha-oxygen-functionalized amides
was achieved. The use of 7-azaindoline amide was crucial to facilitate direct
enolization and subsequent stereoselective addition to imines in a cooperative
catalytic system comprising a soft Lewis acid and Bronsted base. The
operationally simple room-temperature protocol furnished a syn-Mannich adduct
with high stereoselectivity. Divergent functional group transformation of the
amide moiety of the product allowed for expeditious access to enantioenriched syn
configured alpha-hydroxy-beta-amino carboxylic acid derivatives, highlighting the
synthetic utility of the present catalysis.
PMID- 29332387
TI - Proteome-Wide Characterization of Phosphorylation-Induced Conformational Changes
in Breast Cancer.
AB - Because of the close link between protein function and protein folding stability,
knowledge about phosphorylation-induced protein folding stability changes can
lead to a better understanding of the functional effects of protein
phosphorylation. Here, the stability of proteins from rates of oxidation (SPROX)
and limited proteolysis (LiP) techniques are used to compare the conformational
properties of proteins in two MCF-7 cell lysates including one that was and one
that was not dephosphorylated with alkaline phosphatase. A total of 168 and 251
protein hits were identified with dephosphorylation-induced stability changes
using the SPROX and LiP techniques, respectively. Many protein hits are
previously known to be differentially phosphorylated or differentially stabilized
in different human breast cancer subtypes, suggesting that the phosphorylation
induced stability changes detected in this work are disease related. The SPROX
hits were enriched in proteins with aminoacyl-tRNA ligase activity. These
enriched protein hits included many aminoacyl-tRNA synthetases (aaRSs), which are
known from previous studies to have their catalytic activity modulated by
phosphorylation. The SPROX results revealed that the magnitudes of the
destabilizing effects of dephoshporylation on the different aaRSs were directly
correlated with their previously reported aminoacylation activity change upon
dephosphorylation. This substantiates the close link between protein folding and
function.
PMID- 29332390
TI - High Drug Loading and Sub-Quantitative Loading Efficiency of Polymeric Micelles
Driven by Donor-Receptor Coordination Interactions.
AB - Polymeric micelles are extensively used for the delivery of hydrophobic drugs,
which, however, suffer from unsatisfactory drug loading, colloidal uniformity,
formulation stability, and drug release. Herein, we demonstrate a convenient
strategy to prepare micelles with ultrahigh drug loading via the incorporation of
polymer-drug coordination interactions. An amphiphilic copolymer containing
pendant phenylboronic acid as electron acceptor unit was synthesized, which
afforded donor-acceptor coordination with doxorubicin to obtain micelles with
ultrahigh drug loading (~50%), nearly quantitative loading efficiency (>95%),
uniform size, and colloidal stability. Besides, the encapsulated drug can be
effectively and selectively released in response to the high reactive oxygen
species levels in cancer cells, which potentiated the anticancer efficacy and
reduced systemic toxicity. Apart from doxorubicin, the current platform could be
extended to other drugs with electron-donating groups (e.g., epirubicin and
irinotecan), rendering a simple and robust strategy for enabling high drug
loading in polymeric micelles and cancer-specific drug release.
PMID- 29332391
TI - Interconversion of Methyltropyl and Xylyl Radicals: A Pathway Unavailable to the
Benzyl-Tropyl Rearrangement.
AB - The products of an electrical discharge containing toluene are interrogated using
resonance-enhanced multiphoton ionization and laser-induced fluorescence
spectroscopies. A previously unreported electronic spectrum recorded at m/z =
105, with a putative origin band at 26053 cm-1, is assigned to methyltropyl
radical, which appears to be a major product of the toluene discharge, plausibly
arising from CH insertion. All three o-, m-, and p-xylyl isomers are also
identified. These isomers are detected in electrical discharges containing
various xylenes, where it is also found that interconversion occurs: A discharge
of o-xylene produces some m-xylyl; a discharge of m-xylene produces some o-xylyl;
and a discharge of p-xylene produces all three isomers. No alpha-methylbenzyl was
detected, but styrene was. These observations are supported by state-of-the-art
quantum chemical calculations, which reveal an isomerization pathway between
methyltropyl and xylyl radicals for which there is no analogue in the canonical
tropyl-benzyl isomerization.
PMID- 29332392
TI - Transfer Hydrogenation of Aldehydes and Ketones with Isopropanol under Neutral
Conditions Catalyzed by a Metal-Ligand Bifunctional Catalyst [Cp*Ir(2,2'
bpyO)(H2O)].
AB - A Cp*Ir complex bearing a functional bipyridonate ligand [Cp*Ir(2,2'-bpyO)(H2O)]
was found to be a highly efficient and general catalyst for transfer
hydrogenation of aldehydes and chemoselective transfer hydrogenation of
unsaturated aldehydes with isopropanol under neutral conditions. It was
noteworthy that many readily reducible or labile functional groups such as nitro,
cyano, ester, and halide did not undergo any change under the reaction
conditions. Furthermore, this catalytic system exhibited high activity for
transfer hydrogenation of ketones with isopropanol. Notably, this research
exhibited new potential of metal-ligand bifunctional catalysts for transfer
hydrogenation.
PMID- 29332393
TI - Impact of Nonideal Nanoparticles on X-ray Photoelectron Spectroscopic
Quantitation: An Investigation Using Simulation and Modeling of Gold
Nanoparticles.
AB - Quantitative X-ray photoelectron spectroscopic (XPS) analysis combined with
spectral modeling of photoelectrons can be valuable while investigating the
surface chemistry of nanoparticles (NPs) with different morphologies. Herein,
with the use of NIST Simulation of Electron Spectra for Surface Analysis (SESSA),
a comparative analysis of experimental and simulated photoelectron peak
intensities in gold nanoparticles (AuNPs) of different morphologies is presented.
Three sets of supported AuNPs with different morphologies were selected from a
series of as synthesized Au-TiO2 catalyst samples. Using transmission electron
microscopy (TEM) analyzed morphological information on the AuNPs as input model
parameters in SESSA, XPS spectra were generated from the respective input NP
morphologies. A degree of greater mismatch between SESSA simulated and
experimental XPS spectra was observed while using the TEM obtained average
diameter of the nanoparticles. The degree of mismatch lowered when the true
nonspherical shape of the nanoparticles as obtained from TEM images was taken
into account for the simulation. This demonstrates the impact of surface
morphology on the XPS peak intensities which needs to be incorporated to obtain
precise quantified information from the supported nanoparticles. This work
demonstrates the applicability of SESSA in combination with experimental XPS and
TEM measurements for precise quantification of XPS spectra from complex, nonideal
shaped nanoparticles. This study can be extended to include a broad range of
nanoparticles with ideal or nonideal geometries, thus providing a simple method
to utilize quantitative XPS analysis to a wide range of nanomaterials.
PMID- 29332394
TI - Compositional Dependence of Solubility/Retention of Molybdenum Oxides in
Aluminoborosilicate-Based Model Nuclear Waste Glasses.
AB - Molybdenum oxides are an integral component of the high-level waste streams being
generated from the nuclear reactors in several countries. Although borosilicate
glass has been chosen as the baseline waste form by most of the countries to
immobilize these waste streams, molybdate oxyanions (MoO42-) exhibit very low
solubility (~1 mol %) in these glass matrices. In the past three to four decades,
several studies describing the compositional and structural dependence of
molybdate anions in borosilicate and aluminoborosilicate glasses have been
reported in the literature, providing a basis for our understanding of
fundamental science that governs the solubility and retention of these species in
the nuclear waste glasses. However, there are still several open questions that
need to be answered to gain an in-depth understanding of the mechanisms that
control the solubility and retention of these oxyanions in glassy waste forms.
This article is focused on finding answers to two such questions: (1) What are
the solubility and retention limits of MoO3 in aluminoborosilicate glasses as a
function of chemical composition? (2) Why is there a considerable increase in the
solubility of MoO3 with incorporation of rare-earth oxides (for example, Nd2O3)
in aluminoborosilicate glasses? Accordingly, three different series of
aluminoborosilicate glasses (compositional complexity being added in a tiered
approach) with varying MoO3 concentrations have been synthesized and
characterized for their ability to accommodate molybdate ions in their structure
(solubility) and as a glass-ceramic (retention). The contradictory viewpoints
(between different research groups) pertaining to the impact of rare-earth
cations on the structure of aluminoborosilicate glasses are discussed, and their
implications on the solubility of MoO3 in these glasses are evaluated. A novel
hypothesis explaining the mechanism governing the solubility of MoO3 in rare
earth containing aluminoborosilicate glasses has been proposed.
PMID- 29332395
TI - Structure and Reactivity of Half-Sandwich Rh(+3) and Ir(+3) Carbene Complexes.
Catalytic Metathesis of Azobenzene Derivatives.
AB - Traditional rhodium carbene chemistry relies on the controlled decomposition of
diazo derivatives with [Rh2(OAc)4] or related dinuclear Rh(+2) complexes, whereas
the use of other rhodium sources is much less developed. It is now shown that
half-sandwich carbene species derived from [Cp*MX2]2 (M = Rh, Ir; X = Cl, Br, I,
Cp* = pentamethylcyclopentadienyl) also exhibit favorable application profiles.
Interestingly, the anionic ligand X proved to be a critical determinant of
reactivity in the case of cyclopropanation, epoxide formation and the previously
unknown catalytic metathesis of azobenzene derivatives, whereas the nature of X
does not play any significant role in -OH insertion reactions. This perplexing
disparity can be explained on the basis of spectral and crystallographic data of
a representative set of carbene complexes of this type, which could be isolated
despite their pronounced electrophilicity. Specifically, the donor/acceptor
carbene 10a derived from ArC(?N2)COOMe and [Cp*RhCl2]2 undergoes spontaneous 1,2
migratory insertion of the emerging carbene unit into the Rh-Cl bond with
formation of the C-metalated rhodium enolate 11. In contrast, the analogous
complexes 10b,c derived from [Cp*RhX2]2 (X = Br, I) as well as the iridium
species 13 and 14 derived from [Cp*IrCl2]2 are sufficiently stable and allow true
carbene reactivity to be harnessed. These complexes are competent intermediates
for the catalytic metathesis of azobenzene derivatives, which provides access to
alpha-imino esters that would be difficult to make otherwise. Rather than
involving metal nitrenes, the reaction proceeds via aza-ylides that evolve into
diaziridines; a metastable compound of this type has been fully characterized.
PMID- 29332396
TI - Electrochemical System for the Study of Trans-Plasma Membrane Electron Transport
in Whole Eukaryotic Cells.
AB - The study of trans-plasma membrane electron transport (tPMET) in oncogenic
systems is paramount to the further understanding of cancer biology. The current
literature provides methodology to study these systems that hinges upon
mitochondrial knockout genotypes in conjunction with cell surface oxygen
consumption, or the detection of an electron acceptor using colorimetric methods.
However, when using an iron redox based system to probe tPMET, there is yet to be
a method that allows for the simultaneous quantification of iron redox states
while providing an exceptional level of sensitivity. Developing a method to
simultaneously analyze the redox state of a reporter molecule would give
advantages in probing the underlying biology. Herein, we present an
electrochemical based method that allows for the quantification of both
ferricyanide and ferrocyanide redox states to a highly sensitive degree. We have
applied this system to a novel application of assessing oncogenic cell-driven
iron reduction and have shown that it can effectively quantitate and identify
differences in iron reduction capability of three lung epithelial cell lines.
PMID- 29332397
TI - Unconventional Fragment Usage Enables a Concise Total Synthesis of (-)
Callyspongiolide.
AB - An asymmetric synthesis of (-)-callyspongiolide is described. The route builds
the macrolide domain atypically from a disaccharide and a monoterpene without
passing through a seco-acid. Chiral iridium catalysis selectively joins
fragments. Subsequent degradation of an imbedded butyrolactone via perhemiketal
fragmentation affords a stereo- and regio-defined homoallylic alcohol that is
engaged directly in a carbonylative macrolactonization. Further elaboration of
the polyunsaturated appendage provides the natural product in a particularly
direct and flexible manner.
PMID- 29332398
TI - High-Performance Thermoelectric Bulk Colusite by Process Controlled Structural
Disordering.
AB - High-performance thermoelectric bulk sulfide with the colusite structure is
achieved by controlling the densification process and forming short-to-medium
range structural defects. A simple and powerful way to adjust carrier
concentration combined with enhanced phonon scattering through point defects and
disordered regions is described. By combining experiments with band structure and
phonons calculations, we elucidate, for the first time, the underlying mechanism
at the origin of intrinsically low thermal conductivity in colusite samples as
well as the effect of S vacancies and antisite defects on the carrier
concentration. Our approach provides a controlled and scalable method to engineer
high power factors and remarkable figures of merit near the unity in complex bulk
sulfide such as Cu26V2Sn6S32 colusites.
PMID- 29332399
TI - ENDOR-Induced EPR of Disordered Systems: Application to X-Irradiated Alanine.
AB - The electron paramagnetic resonance (EPR) spectra of radiation-induced radicals
in organic solids are generally composed of multiple components that largely
overlap due to their similar weak g anisotropy and a large number of hyperfine
(HF) interactions. Such properties make these systems difficult to study using
standard cw EPR spectroscopy even in single crystals. Electron-nuclear double
resonance (ENDOR) spectroscopy is a powerful and widely used complementary
technique. In particular, ENDOR-induced EPR (EIE) experiments are useful for
separating the overlapping contributions. In the present work, these techniques
were employed to study the EPR spectrum of stable radicals in X-irradiated
alanine, which is widely used in dosimetric applications. The principal values of
all major proton HF interactions of the dominant radicals were determined by
analyzing the magnetic field dependence of the ENDOR spectrum at 50 K, where the
rotation of methyl groups is frozen. Accurate simulations of the EPR spectrum
were performed after the major components were separated using an EIE analysis.
As a result, new evidence in favor of the model of the second dominant radical
was obtained.
PMID- 29332400
TI - Multiscale Kinetic Modeling Reveals an Ensemble of Cl-/H+ Exchange Pathways in
ClC-ec1 Antiporter.
AB - Despite several years of research, the ion exchange mechanisms in chloride/proton
antiporters and many other coupled transporters are not yet understood at the
molecular level. Here, we present a novel approach to kinetic modeling and apply
it to ion exchange in ClC-ec1. Our multiscale kinetic model is developed by (1)
calculating the state-to-state rate coefficients with reactive and polarizable
molecular dynamics simulations, (2) optimizing these rates in a global kinetic
network, and (3) predicting new electrophysiological results. The model shows
that the robust Cl:H exchange ratio (2.2:1) can indeed arise from kinetic
coupling without large protein conformational changes, indicating a possible
facile evolutionary connection to chloride channels. The E148 amino acid residue
is shown to couple chloride and proton transport through protonation-dependent
blockage of the central anion binding site and an anion-dependent pKa value,
which influences proton transport. The results demonstrate how an ensemble of
different exchange pathways, as opposed to a single series of transitions,
culminates in the macroscopic observables of the antiporter, such as transport
rates, chloride/proton stoichiometry, and pH dependence.
PMID- 29332401
TI - Proteomic Profiling of Leishmania donovani Promastigote Subcellular Organelles.
AB - To facilitate a greater understanding of the biological processes in the
medically important Leishmania donovani parasite, a combination of differential
and density-gradient ultracentrifugation techniques were used to achieve a
comprehensive subcellular fractionation of the promastigote stage. An in-depth
label-free proteomic LC-MS/MS analysis of the density gradients resulted in the
identification of ~50% of the Leishmania proteome (3883 proteins detected), which
included ~645 integral membrane proteins and 1737 uncharacterized proteins.
Clustering and subcellular localization of proteins was based on a subset of
training Leishmania proteins with known subcellular localizations that had been
determined using biochemical, confocal microscopy, or immunoelectron microscopy
approaches. This subcellular map will be a valuable resource that will help
dissect the cell biology and metabolic processes associated with specific
organelles of Leishmania and related kinetoplastids.
PMID- 29332402
TI - Monitoring Antimicrobial Mechanisms of Surface-Immobilized Peptides in Situ.
AB - Antimicrobial peptides (AMPs) in free solution can kill bacteria by disrupting
bacterial cell membranes. Their modes of action have been extensively studied,
and various models ranging from pore formation to carpet-like mechanisms were
proposed. Surface-immobilized AMPs have been used as coatings to kill bacteria
and as sensors to capture bacteria, but the interaction mechanisms of surface
immobilized AMPs and bacteria are not fully understood. In this research, an
analytical platform, sum frequency generation (SFG) microscope, which is composed
of an SFG vibrational spectrometer and a fluorescence microscope, was used to
probe molecular interactions between surface-immobilized AMPs and bacteria in
situ in real time at the solid/liquid interface. SFG probed the molecular
structure of surface-immobilized AMPs while interacting with bacteria, and
fluorescence images of dead bacteria were monitored as a function of time during
the peptide-bacteria interaction. It was believed that upon bacteria contact, the
surface-immobilized peptides changed their orientation and killed bacteria. This
research demonstrated that the SFG microscope platform can examine the structure
and function (bacterial killing) at the same time in the same sample environment,
providing in-depth understanding on the structure-activity relationships of
surface-immobilized AMPs.
PMID- 29332403
TI - A rare complication after colonoscopy: a splenic rupture.
AB - Colonoscopy is the gold standard for the study of colorectal pathology. Splenic
injury is a rare but potentially fatal complication to consider. Therefore, we
present two cases whose management was different and we show their clinical
presentation, their diagnosis and their treatment in order to recognize this
complication early to establish early treatment.
PMID- 29332404
TI - Bowel obstruction secondary to deep infiltrating endometriosis of the ileum.
AB - Deep infiltrating endometriosis (DIE) of the ileum is an uncommon lesion that may
be severe in its clinical presentation. Its diagnosis is challenging in the
absence of a gynecological history of endometriosis and because of its anatomical
location. We read the article by Sanchez, Candel, and Albarracin, and now report
an additional case that was managed urgently.
PMID- 29332405
TI - Endoscopic ultrasound-guided choledochoduodenostomy after a failed or impossible
ERCP.
AB - INTRODUCTION: endoscopic ultrasound-guided biliary drainage (EUS-BD) is an
alternative to percutaneous trans-hepatic biliary drainage (PTBD) in cases of
failed endoscopic retrograde cholangiopancreatography (ERCP). METHODS: this is a
retrospective description of six cases of endoscopic ultrasound-guided biliary
drainage via choledochoduodenostomy (EUCD), as well as the clinical
characteristics, endoscopic procedure, complications and monitoring. RESULTS: all
cases had malignant distal biliary obstruction. The procedure was concluded with
good drainage in four out of six patients. Two late complications were recorded
that were caused by stent migration and there were no deaths related with the
procedure. The average monitoring period was six months. CONCLUSIONS: EUCD can be
considered as a valid therapeutic choice in some selected cases and when
performed by a team of expert endoscopists in cases of failed ERCP drainage or as
an alternative to PTBD. However, the procedure has some associated complications.
PMID- 29332406
TI - The morphological and functional diagnosis of a rare entity: lipomatous
pseudohypertrophy of the pancreas.
AB - Lipomatous pseudohypertrophy of the pancreas is a rare entity characterized by a
replacement, focal or diffuse, of the normal pancreatic tissue by mature fatty
tissue. Its definitive diagnosis is made based on histopathologic analysis.
Nevertheless, typical imaging findings can allow a non-invasive diagnosis and
help its clinical approach.
PMID- 29332407
TI - Nutritional deficiency during colonoscopy preparation: the forgotten iatrogeny.
AB - BACKGROUND AND AIMS: bowel preparation for colonoscopy induces a semi-fasting
state, with a potential negative impact on fragile patients. The present study
aims to quantify nutritional deficiency during colonoscopy preparation. METHODS:
this was an observational and cross-sectional study. A convenience sample was
obtained that included adults that underwent colonoscopy after bowel preparation
with Klean-Prep(r) according to the center protocol. Anthropometric evaluation
was performed and nutritional deficiency was calculated via the quantification of
energy and protein intake during the 48 hours prior to the examination which was
compared with the individuals' needs. The association between nutritional
deficiency with the quality of bowel preparation, age and status
(hospitalized/ambulatory) was evaluated. RESULTS: the study included 131 patients
aged 21-91 years (mean 63.6 +/- 13.2 years); 73 cases were male. Malnutrition
reached 67.2% using specific anthropometric tools. A median preparation quality
of six points was found when the Boston Bowel Preparation Scale was considered.
The mean intake 48 hours prior to the procedure was 1,795 kcal and 100 g of
protein. A daily energy intake of less than 50% of the individual needs was
observed in 88 patients and less than 25% in 29 cases. The mean energy and
protein deficiency were 59% (p < 0.01) and 45% (p < 0.01), and there was no
correlation with preparation quality (p > 0.05). Nutritional defiency is similar
in hospitalized and ambulatory patients (p > 0.05), but higher in older
individuals (p = 0.04). CONCLUSIONS: nutritional deficiency during colonoscopy
preparation was significant, more so in older patients, and there was no
correlation with the quality of bowel preparation. We conclude that bowel
preparation regimens should be reformulated with an improved nutritional intake
and the inclusion of nutritional supplements without residues.
PMID- 29332408
TI - Effect of induction chemotherapy on the quality-of-life in patients with advanced
stage tongue cancer by a prospective study.
AB - Abstracts Objective To assess how induction chemotherapy affects the quality-of
life (QoL) in patients with advanced tongue cancer. Methods This prospective
study included patients who were diagnosed with advanced tongue cancer. Each
patient was asked to complete the University of Washington QoL (UW-QoL), version
4, questionnaire preoperatively and at 12 months after surgery. Patients were
divided into two groups based on whether or not they received induction
chemotherapy. Results Of the 192 patients included in the analysis, 145 patients
had received induction chemotherapy. There were no significant differences
regarding age, sex, tumour stage, node stage, flap reconstruction, tumour
resection range and radiotherapy between the two groups. The mean total hospital
cost was significantly higher in patients who underwent induction chemotherapy
compared with those who did not (68 000 versus 44 000 Yuan Renminbi,
respectively). The two groups had similar pre-treatment and post-treatment
composite QoL scores and in the 12 individual domains. Conclusion Induction
chemotherapy had a limited effect on postoperative QoL in patients with advanced
tongue cancers, but it cost significantly more to administer.
PMID- 29332409
TI - High-dose ulinastatin improves postoperative oxygenation in patients undergoing
aortic valve surgery with cardiopulmonary bypass: A retrospective study.
AB - Objective To determine whether pre-treatment with high-dose ulinastatin provides
enhanced postoperative oxygenation in patients who have undergone aortic valve
surgery with moderate hypothermic cardiopulmonary bypass (CPB). Methods Patients
who underwent aortic valve surgery with moderate hypothermic CPB were
retrospectively evaluated. In total, 94 of 146 patients were included. The
patients were classified into one of two groups: patients in whom ulinastatin
(10,000 U/kg followed by 5,000 U/kg/h) was administered during CPB (Group U, n =
38) and patients in whom ulinastatin was not administered (Group C, n = 56). The
PaO2/FiO2 ratio was calculated at the following time points: before CPB (pre
CPB), 2 h after weaning from CPB (post-CPB), and 6 h after arrival to the
intensive care unit (ICU-6). The incidence of a low PaO2/FiO2 ratio was also
compared among the time points. Results Group U showed a significantly higher
PaO2/FiO2 ratio (F(4, 89.0) = 657.339) and a lower incidence of lung injury
(PaO2/FiO2 ratio < 300) than Group C at the post-CPB and ICU-6 time points.
Conclusion High-dose ulinastatin improved pulmonary oxygenation after CPB and in
the early stages of the ICU stay in patients undergoing aortic valve surgery with
CPB.
PMID- 29332410
TI - Myocardial strain/stress changes identified by echocardiography may reveal early
sepsis-induced myocardial dysfunction.
AB - Objective To perform early assessment of sepsis-induced myocardial dysfunction
(SIMD) using strain/stress echocardiography. Methods A canine model of SIMD was
established using intravenous injection of lipopolysaccharide (LPS, 2 mg/kg).
Thirteen dogs were included, comprising an LPS-treated SIMD group ( n = 7) and
saline control group ( n = 6). SIMD was assessed at various time-points using
cardiac measurements including haemodynamics and echocardiography. Results
Systolic and radial ventricular wall stress and circular ventricular wall stress
(WSsc) were significantly lower in the sepsis group versus the control group at
all time-points. Logistic regression analysis revealed an inverse correlation
between stress rate of the front-posterior and bottom wall and left ventricle
systolic wall strength. In contrast, a positive correlation was found between the
mean velocity of circumferential fibre shortening (mVCF) or heart rate-adjusted
mVCF (RVCF) and WSsc. Using regression equations, predicted values for mVCF and
RVCF in animals with sepsis were significantly higher than measured values at 4-
5- and 6-h time-points. Conclusions These findings will further the understanding
of pathophysiological alterations in SIMD at the early stage of sepsis, and
suggest that strain rate may reflect the nature of myocardial contractility.
PMID- 29332412
TI - [Investigation of the burnout syndrome among the employees of the Department of
Emergency Medicine at the University of Szeged].
AB - INTRODUCTION: Burnout has been described as a growing problem amongst healthcare
workers. Emergency department staffs experience the burden of stress day by day,
yet only a few studies have examined their burnout. AIM: In this study we wanted
to investigate the burnout and its relations to other variables amongst the
employees of the Department of Emergency Medicine in Szeged. METHOD: Cross
sectional design utilizing a self-administered questionnaire was used to collect
data from the staff of the Department. Burnout was measured using the Maslach
Burnout Inventory. RESULTS: Burnout is considerably prevalent among the workers
of the Emergency Department, especially nurses and physicians. The study found
negative relation between burnout and age, number of children, number of years in
the healthcare system, number of physical symptoms, social support and
psychological immune system. Being single was a risk factor. CONCLUSIONS: The
risks and protective factors found to be associated with burnout in this study
might help to set up institutional prevention and intervention strategies. Orv
Hetil. 2018; 159(3): 113-118.
PMID- 29332411
TI - beta1 integrin-mediated multicellular resistance in hepatocellular carcinoma
through activation of the FAK/Akt pathway.
AB - Objective To explore the role and mechanism of beta1 integrin in the regulation
of multicellular drug resistance in hepatocellular carcinoma (HCC). Methods This
in vitro study used a liquid overlay technique to obtain multicellular spheroids
of two human HCC cell lines, HepG2 and Bel-7402. The morphology of the spheroids
was observed by optical and electron microscopy. The effects of exposure to 5
fluorouracil (5-FU) and cisplatin (CDDP) on cell proliferation and the induction
of apoptosis were assessed in monolayer cells and multicellular spheroids. The
levels of beta1 integrin and the effects on the focal adhesion kinase
(FAK)/protein kinase B (Akt) pathway were evaluated using Western blot analysis,
immunofluorescence and flow cytometry. The role of beta1 integrin was confirmed
by using an inhibitory antibody. Results Cell proliferation inhibition and cell
apoptosis induced by 5-FUl and CDDP were abrogated in multicellular spheroids
compared with monolayer cells. There were high levels of beta1 integrin in
multicellular spheroids. beta1 integrin inhibitory antibody prevented the
formation of multicellular spheroids, coupled with a significant increase in
proliferation inhibition and apoptosis induction. beta1 integrin inhibitory
antibody effectively suppressed activation of both FAK and Akt in multicellular
spheroids. Conclusions beta1 integrin mediated multicellular drug resistance
through the FAK/Akt pathway in HCC spheroids.
PMID- 29332414
TI - [Interatrial block and its clinical relevance. Renaissance of an ECG change].
AB - Interatrial block involves conduction delay between the right and left atria
during sinus rhythm. The review describes the classification, pathomechanism and
clinical significance of this under-recognised ECG sign, nominated Bayes
syndrome. The presented ECGs help to recognise the differentypes of interatrial
blocks. Orv Hetil. 2018; 159(3): 91-95.
PMID- 29332415
TI - [Prognostic importance of albumin in oncology].
AB - Diminished serum albumin level can be observed in inflammatory processes. Serum
albumin level also reduces - irrespective of the presence of malnutrition - in
locally advanced or metastatic malignancies. Low serum albumin level may have an
influence also on the results of anticancer therapy (e.g., drug pharmacokinetics,
adverse drug reactions). Extensive data of the literature and empirical
experience prove the better prognosis of patients involved in nutritional
therapy. Based on the most relevent data of the literature, the authors summarize
the studies which have revealed the close correlation between the baseline serum
albumin level and the prognosis of malignant diseases. Orv Hetil. 2018; 159(3):
96-106.
PMID- 29332416
TI - [Autoimmune encephalitis: possibilities in the laboratory investigation].
AB - INTRODUCTION: The role of autoimmune responses against central nervous system
(CNS) antigens in encephalitis presenting with non-classified neurologic or
psychiatric symptoms has been appreciated in the past decade. Paraneoplastic
limbic encephalitis has a poor prognosis and is most commonly associated with
lung, ovarium, and testicular neoplasms, leading to immune reactions against
intracellular antigens (anti-Hu/ANNA1, anti-Ri/ANNA2, anti-CV2/CRMP5 and anti
Ma2/Ta). In contrast, the recently described autoimmune encephalitis subtypes
present with a broad spectrum of symptoms, respond to autoimmune therapies well
and usually associate with autoantibodies against neuronal cell surface receptors
(NMDAR, GABABR, AMPAR) or synaptic proteins (LGI1, CASPR2). AIM: Our aim is to
bring to awareness the increasing number of autoimmune encephalitis patients
requiring neurologic, psychiatric and intensive care and to emphasize the
significance of detecting various autoantibodies in diagnosing patients. METHOD:
In the past 6 years, our laboratory received 836 autoimmune encephalitis
diagnostic test requests from a total of 717 patients. Serum and cerebrospinal
fluid (CSF) samples were analysed with indirect immunofluorescence using a
BIOCHIP consisting of cell lines transfected with 6 different receptor proteins.
RESULTS: IgG autoantibodies against receptor proteins were present in 7.5% of
patients. The frequency of positive samples was the following: NMDAR > LGI1 >
GABABR > CASPR2. CONCLUSION: Detecting autoantibodies facilitates the diagnosis
of autoimmune encephalitis in an early stage. Patients diagnosed early can be
effectively treated with plasmapheresis and immunosuppressive drugs. The
efficiency of therapies can be monitored by autoantibody detection. Therefore,
the diagnostic immune laboratory plays an important role in proper diagnosis and
in the prevention of rapidly progressing symptoms. Orv Hetil. 2018; 159(3): 107
112.
PMID- 29332417
TI - [Concise history of toxicology - from empiric knowledge to science].
AB - Toxicology is a science of poisonings by xenobiotics and endogenous physiological
changes. Its empiric roots may be traced back to the emerging of the human race
because the most important pledge of our predecessors' survival was the
differentiation between eatable and poisonous plants and animals. In the course
of social evolution, there were three main fields of using poisons: 1) hunting
and warfare, 2) to settle social tensions by avoiding military conflicts through
hiding strategy of eliminating enemies by toxic substances, 3) medicines applied
first as anti-poisons and later by introducing strong substances to defeat
diseases, but paradoxically active euthanasia is also a part of the whole story.
The industrial revolution of the 19th century changed the sporadic occupational
diseases to mass conditions. Later the chemical industry and subsequently the
mass production of synthetic materials turned out as a global environmental
catastrophe. This latest change initiated the emerging of ecological toxicology
which is a future history of the concerning ancient science. Orv Hetil. 2018;
159(3): 83-90.
PMID- 29332419
TI - Adolescent Stress Treatment Study: A Cluster Randomized Trial.
AB - High school students experience a variety of stressors. Mental health issues are
critical to their health. The "Adolescent Stress Treatment (AST) Study: A Cluster
Randomized Trial" compared the efficacy of two stress reduction devices, the
EnergyPodTM and the SleepWingTM. The EnergyPodTM is a device that provides a
semiprivate acoustical and visual environment for rest, stress reduction, and
sleep. The SleepWingTM is a smaller device offering similar benefits. High school
students were offered the opportunity to participate in the AST study when they
exhibited signs of agitation. The students completed the Profile of Mood States
Short Form (POMS-SF) pre- and postintervention. Total Mood Disturbance (TMD) was
measured from the POMS-SF and significant improvement postintervention ( p <
.001), regardless of intervention used. POMS-SF subscales were all significantly
improved no matter which device was used. All participants in the study
dramatically improved their mood after being in either therapeutic device.
PMID- 29332418
TI - The role of PET and MRI in evaluating the feasibility of skin-sparing mastectomy
following neoadjuvant therapy.
AB - Objective To investigate the role of positron emission tomography (PET) and
magnetic resonance imaging (MRI) in evaluating the feasibility of skin-sparing
mastectomy in patients with locally-advanced breast cancer (LABC) who will
undergo neoadjuvant chemotherapy (NAC) by evaluating the sensitivity and
specificity of PET and MRI compared with skin biopsy results before and after NAC
treatment. Methods Patients with LABC who were treated with NAC between November
2013 and November 2015 were included in this study. Demographic, clinical,
radiological and histopathological features of the patients were recorded.
Results A total of 30 patients were included in the study with a mean age of 52.6
years (range, 35-70 years). Sensitivity and specificity for detecting skin
involvement in LABC was 100%/10% (62%/85%) with MRI and 60%/80% (12%/92%) with
PET before (after) NAC, respectively. When radiological skin involvement was
assessed in relation to the final histopathological results, the preNAC PET
results and histopathological skin involvement were not significantly different;
and there was no difference between postNAC MRI and histopathological skin
involvement. Conclusions As preNAC PET and postNAC MRI more accurately determined
skin involvement, it might be possible to use these two radiological evaluation
methods together to assess patient suitability for skin-sparing mastectomy in
selected patients.
PMID- 29332420
TI - Activated Factor 7 Versus 4-Factor Prothrombin Complex Concentrate for Critical
Bleeding Post-Cardiac Surgery.
AB - BACKGROUND: Recombinant and plasma-derived factor products, such as activated
factor seven (rFVIIa) and four-factor prothrombin complex concentrate (4-factor
PCC), have been used off-label for bleeding after cardiac surgery, but little
evidence has been published regarding their efficacy and safety. OBJECTIVE: To
determine whether there is a difference in chest tube output in patients who have
received 4-factor PCC or rFVIIa for critical postoperative bleeding associated
with cardiovascular surgery. METHODS: A retrospective chart review was conducted
utilizing the electronic medical record system at a 657-bed community, tertiary
care hospital in Nashville, Tennessee. Nonpregnant patients >=18 years of age
experiencing significant bleeding during cardiac surgery who received either PCC
or rFVIIa perioperatively or postoperatively between April 2015 through December
2016 were eligible for inclusion. Patients were excluded if they received 4
factor PCC or rFVIIa for any indication other than bleeding during cardiac
surgery or if they received both agents. RESULTS: Data conclude that there is no
significant difference in chest tube output 24 hours postoperatively between
patients treated with 4-factor PCC or rFVIIa. There was no difference in
bleeding, thromboembolic events, or re-exploration between the rFVIIa and 4
factor PCC groups, but there was a difference in units of fresh frozen plasma
administered and hospital length of stay. CONCLUSION: 4-Factor PCC may be an
equally efficacious alternative to rFVIIa for patients experiencing significant
bleeding during cardiac surgery. There is no difference in chest tube output;
therefore, there is no difference in bleeding-either at 24 hours postoperatively
or total.
PMID- 29332421
TI - Comparison of Two Weight-Based Desmopressin Dosing Strategies for Spontaneous
Bleeding.
AB - BACKGROUND: The pharmacokinetics and pharmacodynamics of desmopressin are
appropriate for adjusted body weight-based dosing, particularly in obese
patients. OBJECTIVE: The objective of this study was to describe desmopressin
dosing strategies, with emphasis on hemostatic outcomes among patients without
preexisting bleeding disorders. METHODS: This was a single-center, retrospective
cohort study of patients who received intravenous weight-based desmopressin for a
hemostatic indication. Demographics, comorbidities, treatment setting,
indication, site of bleeding, and outcomes were collected from the medical
record. Primary outcomes included need for procedural intervention to achieve
hemostasis, transfusion requirement, and death. Association between desmopressin
dose and outcome was evaluated using chi2 or Fischer's exact tests and logistic
and linear regression models. Multiple regression analysis was conducted to
identify other predictors of outcome in the data set. RESULTS: A total of 109
patients were included (n = 26, dose adjustment; n = 83, no dose adjustment).
Baseline characteristics were well-matched between groups: mean (SD) age of 57.0
(13.5) years; mean (SD) Charlson Comorbidity Score of 6.5 (2.8); 37% were obese;
76% were critically ill; 81% were actively bleeding without differences in site
of bleeding; and crude mortality was 39%. No differences in death, mean units of
packed red blood cells transfused, or need for procedural hemostasis were
observed between adjusted weight- and actual weight-based desmopressin dosing.
CONCLUSIONS: When used adjunctively to blood product transfusion in actively
bleeding patients, use of adjusted body weight-based desmopressin did not
negatively affect clinical outcomes. More data are needed to confirm this dosing
strategy.
PMID- 29332422
TI - Unexpected Management Behaviors in Adolescents With Type 1 Diabetes Using Sensor
Augmented Pump Therapy.
AB - BACKGROUND: Continuous glucose monitoring can improve glycemic outcomes in
individuals with type 1 diabetes. However, the constant exposure to real-time
glucose levels can sometimes lead the individual to make some risky choices to
address the glycemic excursions. Hence, the purpose of this study was to explore
the aberrant management behaviors of youth with type 1 diabetes on sensor
augmented pump therapy (SAPT). METHODS: Participants in a clinical trial using
SAPT on Medtronic MiniMedTM 640G pump who experienced deteriorating glycemic
control or unexplained hypoglycemia were identified by the health care
professional. The pump and/or sensor data uploaded to CareLinkTM Therapy
Management Software were reviewed in these participants. RESULTS:
Uncharacteristic management behaviors were identified in five adolescent males.
Continuous exposure to high glucose levels resulted in obsessive behaviors
displaying a perfectionistic attitude in two participants. Multiple boluses were
delivered frequently as uneaten carbohydrates in participant 1 while participant
2 resorted to delivery of extra insulin by cannula fills. In contrast,
participant 3 chose to remain hyperglycemic to avoid weight gain while
participant 4 trusted the system and used sensor glucose readings for
calibrations, with resultant deterioration in glycemic control in both
participants. On the other hand, participant 5, due to mistrust in the pump
suspend function, consumed carbohydrates with downward glucose trends with
rebound hyperglycemia. CONCLUSIONS: Constant exposure to real-time data can lead
to unsafe management responses in adolescents with the behavior influenced by
trust or mistrust in the system. Adolescents should be empowered with problem
solving strategies for safe management.
PMID- 29332423
TI - First Experiences With a Wearable Multisensor in an Outpatient Glucose Monitoring
Study, Part I: The Users' View.
AB - BACKGROUND: Extensive past work showed that noninvasive continuous glucose
monitoring with a wearable Multisensor device worn on the upper arm provides
useful information about glucose trends to improve diabetes therapy in controlled
and semicontrolled conditions. METHODS: To test previous findings also in
uncontrolled in-clinic and outpatient conditions, a long-term study has been
conducted to collect Multisensor and reference glucose data in a population of 20
type 1 diabetes subjects. A total of 1072 study days were collected and a fully
on-line compatible algorithmic routine linking Multisensor data to glucose
applied to estimate glucose trends noninvasively. The operation of a digital log
book, daily semiautomated data transfer and at least 10 daily SMBG values were
requested from the patient. RESULTS: Results showed that the Multisensor is
capable of indicating glucose trends. It can do so in 9 out of 10 cases either
correctly or with one level of discrepancy. This means that in 90% of all cases
the Multisensor shows the glucose dynamic to rapidly increase or at least
increase. CONCLUSIONS: The Multisensor and the algorithmic routine used in
controlled conditions can track glucose trends in all patients, also in
uncontrolled conditions. Training of the patient proved to be essential. The
workload imposed on patients was significant and should be reduced in the next
step with further automation. The feature of glucose trend indication was
welcomed and very much appreciated by patients; this value creation makes a
strong case for the justification of wearing a wearable.
PMID- 29332424
TI - Salivary metabolomics profile of patients with recurrent aphthous ulcer as
revealed by liquid chromatography-tandem mass spectrometry.
AB - Objective We compared the salivary nontargeted metabolite profiles between
patients with recurrent aphthous ulcer (RAU) and healthy individuals to
investigate the metabolic alterations associated with RAU. Methods Saliva samples
were collected from 45 patients with RAU and 49 healthy individuals, and the
salivary metabolites were quantified using liquid chromatography-tandem mass
spectrometry. The metabolomic profiles were then analyzed using multivariate and
univariate statistical methods, and enrichment of the metabolites in various
biological pathways was assessed. Results In total, 206 significant
differentiating metabolites (Wilcoxon test, false discovery rate [FDR] of <0.05)
were identified between patients with RAU and healthy individuals. These
metabolites were implicated in tryptophan metabolism, steroid hormone
biosynthesis, and other metabolic pathways. Two commonly circulating steroids,
estrone sulfate and dehydroepiandrosterone sulfate, were significantly lower in
the saliva of patients with RAU (Wilcoxon test, FDR < 0.05, power > 0.9).
Principal component analysis and partial least-squares discriminant analysis
revealed metabolic perturbations involving RAU, and receiver operating
characteristic curve analysis with several metabolites showed good diagnostic
ability for RAU. Conclusions The results of this study indicate that patients
with RAU are characterized by metabolic imbalances. Psychogenic factors,
endocrinopathies, and immunosuppression may contribute to the onset of RAU.
PMID- 29332425
TI - Dermatological Manifestations in Patients Undergoing In Vitro Fertilisation: A
Prospective Study.
AB - BACKGROUND: Changing sociodemographic patterns with an increase in the age of
childbirth have affected fertility rates worldwide. With advancing reproductive
medicine, assisted reproductive techniques (ARTs) are becoming common. While
dermatological manifestations in normal pregnancies have been well documented,
there is a paucity of data regarding cutaneous manifestations in patients
undergoing ART. OBJECTIVES: The objectives of our study were to estimate the
incidence and types of dermatological manifestations in patients undergoing in
vitro fertilisation (IVF) and to study their associations with age, type of
infertility, and outcome of the procedure. METHODS: A prospective cohort of 200
patients undergoing IVF in a tertiary care centre was observed for occurrence of
any dermatological manifestations from initiation of the IVF protocol to the
outcome of the procedure at 3 weeks after embryo transfer. RESULTS:
Dermatological manifestations were seen in 27% of the study group, with urticaria
being the most common cutaneous finding seen in 13.5%, followed by acneform
eruptions (3%). Twenty-six (96.3%) of patients who manifested with urticaria were
on progesterone. No statistically significant association was found between the
occurrence of dermatological manifestations and the outcome of IVF, type of
infertility, history of ART, and ovum donation in our study. Association between
the age of the patient and the outcome of IVF cycle was statistically
significant. CONCLUSION: Dermatological manifestations are seen in almost one
quarter of patients undergoing IVF, with progesterone-induced urticaria being the
most common. Occurrence of cutaneous manifestations has no significant
association with the outcome of IVF.
PMID- 29332426
TI - Effects of multiple sclerosis and medications on menopausal age.
AB - Objectives We aimed to determine whether multiple sclerosis (MS) and
methylprednisolone and disease-modifying drugs have an effect on menopausal age.
Methods A total of 86 patients and 98 healthy subjects were included in this
study. The natural menopausal age of the patients and healthy subjects were
compared. The cumulative dosages of methylprednisolone, beta interferons
(IFNbetas), and glatiramer acetate were calculated. The effects of the Expanded
Disability Status Scale (EDSS), duration of the disease, and cumulative dosage of
medications on menopausal age were evaluated. Results The patients' mean
menopausal age was 45.3 +/- 4.8 years and healthy subjects' menopausal age was
46.8 +/- 4.3 years, with no significant difference between the two groups. The
cumulative dosage of methylprednisolone showed an effect on menopausal age. There
was a significant inverse correlation between menopausal age and dosage of
IFNbeta-1b, while the disease duration and EDSS score showed no correlation with
menopausal age. Conclusions We conclude that menopausal age is not affected by
MS. However, long-term methylprednisolone and IFNbeta-1b treatments may change
menopausal age in a dose-dependent manner.
PMID- 29332427
TI - Serum potassium levels and outcomes in critically ill patients in the medical
intensive care unit.
AB - Objective To compare the outcomes of patients with and without a mean serum
potassium (K+) level within the recommended range (3.5-4.5 mEq/L). Methods This
prospective cohort study involved patients admitted to the medical intensive care
unit (ICU) of Siriraj Hospital from May 2012 to February 2013. The patients'
baseline characteristics, Acute Physiology and Chronic Health Evaluation II
(APACHE II) score, serum K+ level, and hospital outcomes were recorded. Patients
with a mean K+ level of 3.5 to 4.5 mEq/L and with all individual K+ values of 3.0
to 5.0 mEq/L were allocated to the normal K+ group. The remaining patients were
allocated to the abnormal K+ group. Results In total, 160 patients were included.
Their mean age was 59.3+/-18.3 years, and their mean APACHE II score was 21.8+/
14.0. The normal K+ group comprised 74 (46.3%) patients. The abnormal K+ group
had a significantly higher mean APACHE II score, proportion of coronary artery
disease, and rate of vasopressor treatment. An abnormal serum K+ level was
associated with significantly higher ICU mortality and incidence of ventricular
fibrillation. Conclusion Critically ill patients with abnormal K+ levels had a
higher incidence of ventricular arrhythmia and ICU mortality than patients with
normal K+ levels.
PMID- 29332428
TI - The Effectiveness of Preoperative Preparation for Improving Perioperative
Outcomes in Children and Caregivers.
AB - Most children experience significant anxiety during the preoperative period.
Greater preoperative anxiety may be related to a higher incidence of negative
behaviors. This study aimed to develop a family-centered preoperative preparation
program and to evaluate the effects of this program on children's preoperative
emotional behaviors, postoperative behavior, and posthospital behavior, and on
caregiver anxiety. A prospective, randomized controlled study was conducted. The
population consisted of children who underwent minor surgery and their
caregivers. The control group received standard care, and the experimental group
received standard care plus preoperative preparation, which included a tour, a
cartoon video depicting a boy's surgical journey, and familiarization with
medical equipment. Children's emotional behaviors and caregiver anxiety were
measured at the preoperative visit, in the preoperative holding area, and at
induction of anesthesia. Postoperative behavior was measured when children were
in the recovery room, and the researcher also contacted caregivers 2 weeks after
the surgery to assess the children's behavior at home. A linear mixed-effects
model results showed that as the surgery approached, the experimental group had
fewer and more stable preoperative emotional behaviors (least squares means of
preoperative emotional behaviors from preoperative visit to induction of
anesthesia = 10.01-10.95). However, the control group exhibited significantly
increased preoperative emotional behaviors as the surgery approached (least
squares means of preoperative emotional behaviors from the preoperative visit to
induction of anesthesia = 7.87-12.23). Family-centered preoperative preparation
can effectively improve children's negative emotional behaviors from their time
in the preoperative holding area to the induction of anesthesia.
PMID- 29332429
TI - Engagement as predictors of performance in a single cohort of undergraduate
chiropractic students.
AB - OBJECTIVE: To investigate the potential association of novel academic and
nonacademic factors with chiropractic student academic performance. METHODS:
Students enrolled into year 1 of a chiropractic master's degree (MChiro) at our
college were selected for this study. Data collected included demographics,
attendance, virtual learning environment use, additional learning needs, previous
degree qualifications, and summative marks. Differences between students who had
to take an examination more than once (resit) and nonresit students were explored
using t test and chi2 analysis. Relationships between attendance and end-of-year
marks were explored using regression analysis. RESULTS: Male students
outperformed female students in four of the six units and as the total year
average. Students who attended <80% of classes were more likely to have a resit
in one or more units (relative risk [ RR] = 2.6; 95% confidence interval [CI],
1.4-4.9). Students who performed poorly (<70%) in the semester 1 unit of a course
on human structure and failed the semester 1 practical assessment of a course on
clinical management were significantly more likely to have one or more resit
assessments in semester 2 units ( RR = 3.5 [95% CI, 2.2-5.7]; RR = 3.2 [95% CI,
2.0-4.9]). Attendance and unit 105 were independent predictors of one or more
resits at the end-of-year ( R2 = 0.86, p < .001). CONCLUSION: Attendance and
first semester summative marks were associated with end-of-year performance. As
such, these markers of performance may be used to flag struggling students in the
program.
PMID- 29332431
TI - Validation of the Ceredigion Youth Screening Tool.
AB - Evidence suggests that only a small minority of youth offenders will continue
their behaviour in the longer term and largely independent of any interventions
they may receive (Bateman, 2011; Haines & Case, 2015). Hence, "screening out"
this larger low-risk cohort could have a positive impact upon the individual
through a reduction in stigmatisation/labelling and free up resources for higher
risk clients. This article outlines development of the Ceredigion Youth Screening
Tool (CYSTEM)-developed and tested to address the two facets of criminality and
vulnerability-closely aligned to the eight key risk indicators identified in the
Risk-Needs-Responsivity (R-N-R) literature (Andrews & Bonta, 2010). Initial
results with two cohorts of 372 young people indicate good convergent and
discriminative validity in screening out the lowest level referrals, while also
identifying 90% of potential future offenders. More importantly, CYSTEM is able
to screen out approximately 35% of the low-risk offenders that are unlikely to
require formal evaluation and/or intervention. It is suggested that the
streamlining of this process using CYSTEM reduces demand on staff time and
decreases the stigmatisation of young people referred for minor offences.
Potential improvements to the tool and future developments in statistical risk
prediction are also discussed.
PMID- 29332430
TI - Effect of creatine phosphate sodium on bispectral index and recovery quality
during the general anaesthesia emergence period in elderly patients: A
randomized, double-blind, placebo-controlled trial.
AB - Objective To evaluate the effect of creatine phosphate sodium on bispectral index
(BIS) and recovery quality during the general anaesthesia emergence period in
elderly patients. Methods This randomized, double-blind, placebo-controlled study
enrolled patients undergoing transabdominal cholecystectomy under general
anaesthesia. Patients were randomly assigned to receive either creatine phosphate
sodium (1.0 g/100 ml 0.9% saline; group P) or 100 ml 0.9% saline (group C) over
30 minutes during surgical incision. The BIS values were recorded at anaesthesia
induction (T0), skin incision (T1), cutting the gallbladder (T2), suturing the
peritoneum (T3), skin closure (T4), sputum suction (T5), extubation (T6) and 1
min (T7), 5 min (T8), 10 min (T9), and 15 min (T10) after extubation. The
anaesthesia duration, operation time, waking time, extubation time, consciousness
recovery time, time in the postanaesthesia care unit (PACU), and the Steward
recovery scores at T7, T8, T9 and T10 were recorded. Results A total of 120
elderly patients were randomized equally to the two groups. Compared with group
C, the BIS values were significantly higher in group P at T5, T6, T7 and T8; and
the Steward recovery scores at T7 and T8 were significantly higher in group P.
The waking time, extubation time, consciousness recovery time and time in the
PACU were significantly shorter in group P compared with group C. Conclusion
Creatine phosphate sodium administered during transabdominal cholecystectomy can
improve BIS values and recovery following general anaesthesia in elderly
patients.
PMID- 29332433
TI - Slippage of Tightrope Button in Syndesmotic Fixation of Weber C Malleolar
Fractures: A Case Series.
AB - BACKGROUND: Tightrope fixation is an emerging technique for syndesmotic fixation
with promising results. However, our case series highlights the slippage of
Tightrope buttons as a complication of suture button syndesmotic fixation of
Weber C malleolar fractures using limited contact dynamic compression (LCDCP)
plates. METHODS: We report a series of cases from our database in which slippage
of the Tightrope button through the LCDCP holes in Weber C malleolar fractures
was noted. We measured the medial clear space (MCS), tibiofibular clear space
(TFCS), and distal tibiofibular overlap (DTFO) and computed the largest change in
these measurements from the first postoperative follow-up radiographs. Patient
records were reviewed for persistent symptoms that could be attributed to the
loss of syndesmotic fixation and stability. RESULTS: Follow-up radiographs of 3
patients showed a slippage of the Tightrope button through the LCDCP holes. Two
of the patients reported persistent ankle pain and swelling with prolonged
activity. The mean increases in MCS and TFCS among these patients were 0.7 (+/
0.081) mm and 1.5 (+/-0.798) mm, respectively. The mean decrease in DTFO was 2.2
(+/-0.864) mm. We next highlight 3 patients with Weber C malleolar fractures who
underwent suture button syndesmotic fixation using double-stacked one-third
tubular plates instead of the LCDCP. CONCLUSION: This case series reported
Tightrope button slippage as an early complication of syndesmotic fixation of
Weber C malleolar fractures. We propose the use of double-stacked one-third
tubular plates instead of the LCDCP to avoid this complication. LEVEL OF
EVIDENCE: Level V, expert opinion.
PMID- 29332432
TI - Spontaneous fetal femoral fracture: a case report and literature review.
AB - Spontaneous fetal femoral fractures are uncommon in the paediatric setting. The
major clinical presentations of a spontaneous fetal femoral fracture are femoral
angulation, shortness of the femur and even a marked fracture line. This case
report describes a spontaneous fetal femoral fracture of the right femur, which
was detected by routine ultrasonography during the 19th week of gestation in a 24
year-old woman. On routine follow-up visits, the angulation of the right femur in
the fetus gradually improved. A caesarean section was undertaken at 39 weeks +5
days of gestation and an X-ray was taken on the second day after birth, which
showed that the fracture had healed and the callus had been absorbed. The lengths
of the two femurs of the baby were not equal; the right femur was 84 mm, which
was 11 mm shorter than the left femur. In cases like this, postnatal follow-up is
essential so that an operation can be carried out in a timely manner when the
deformity is apparent.
PMID- 29332435
TI - CHANGES IN THE HEMOCYTE PICTURE OF GALLERIA MELLONELLA (LINNAEUS).
AB - 1. The hemocytes of Galleria mellonella (Linnaeus) larvae were identified and
differentially counted in unfixed hemolymph with phase microscopy. The numbers of
hemocytes per microliter of hemolymph were obtained from both unfixed and heat
fixed larvae. Hemolymph volumes were determined by the amaranth red method. These
studies were made to determine what changes in the hematology occur as the last
stage larvae pass through distinctive phases in transforming into pupae. 2. In
differential counts, plasmatocytoids decrease, immature adipohemocytes suddenly
appear, and mature adipohemocytes steadily increase. Spherule cells, oenocytoids
and dividing hemocytes decrease as Galleria larvae develop into pupae. 3. The
numbers of hemocytes per microliter of hemolymph increase as Galleria larvae
proceed towards the pupal stage in both unfixed and heat-fixed animals. Counts
were always significantly higher in heat-fixed than in unfixed larvae. 4. The
hemolymph volume is the same in both unfixed and heat-fixed larvae. The hemolymph
volume declines from about 34% (56.7 microliters) in precocoonspinning larvae to
less than 16.4% (19 microliters) in newly formed pupae. 5. It is estimated from
the various data presented that an average of 1,456,000 hemocytes remain in
circulation within the hemocoele of unfixed larvae from the fifteenth through the
twentieth days of life, and that with pupation more than one-half of these cells
fall out of circulation. 6. In three out of 5 cases it was possible to correlate
decreases in the plasmatocytoid population with increases in adipohemocytes. It
is suggested that during the spinning of a cocoon plasmatocytoids transform into
both immature and mature adipohemocytes, that when the larvae are densely
cocooned mature adipohemocytes are largely formed by the maturation of immature
adipohemocytes, and that in pharate pupae new mature adipohemocytes are derived
from both immature adipohemocytes and plasmatocytoids. 7. The hemocyte picture of
Galleria is compared to that of Prodenia and Bombyx. In all three of these
Lepidoptera the plasmatocytoids decrease and the hemocytes with many
polysaccharide and/or lipid or other types of inclusions increase prior to
pupation. Galleria differs from the other two species in that their hemocytes
with lipid or other inclusions do not appear until about the sixteenth or
seventeenth days of larval life, do not divide, and in many cases are derived
from circulating plasmatocytes.
PMID- 29332434
TI - Relationship between antimicrobial-resistance programs and antibiotic dispensing
for upper respiratory tract infection: An analysis of Australian data between
2004 and 2015.
AB - Objective NPS MedicineWise aims to ensure that medicines are prescribed and used
in a manner consistent with current evidence-based best practice. A series of
nationwide educational and advertising interventions for general practitioners
and consumers were implemented in Australia between 2009 and 2015 with the aim of
reducing antibiotic prescriptions for upper respiratory tract infections (URTIs).
The work described in this paper quantifies the change in antibiotic dispensing
following these interventions. Methods Antibiotic dispensing data between 2004
and 2015 were obtained from a national claims database. A Bayesian structural
time series model was used to forecast a series of antibiotic dispensing volumes
expected to have occurred if the interventions had not taken place. These were
compared with the volumes that were actually observed to estimate the
intervention effect. Results On average, 126,536 fewer antibiotics were dispensed
each month since the intervention programs began in 2009 (95% Bayesian credible
interval = 71,580-181,490). This change represents a 14% total reduction in
dispensed scripts after the series of intervention programs began in 2009.
Conclusions Continual educational intervention programs that emphasise the
judicious use of antibiotics may effectively reduce inappropriate prescribing of
antibiotics for the treatment of URTIs at a national level.
PMID- 29332436
TI - UTILIZATION OF DISSOLVED EXOGENOUS NUTRIENTS BY THE STARFISHES, ASTERIAS FORBESI
AND HENRICIA SANGUINOLENTA.
AB - 1. Small specimens of A. forbesi and H. sanguinolenta were exposed to dissolved
C14-amino acids and glucose. The subsequent distribution of these materials was
then determined in the following five regions of the body: disk (including the
gonads), oral body wall of the rays, aboral body wall of the rays, stomach, and
digestive glands. 2. In all cases, large proportions of the labeled nutrients
were taken up into the external tissues. The largest amount was usually absorbed
into the oral body wall, which probably possesses a proportionately greater
ventilated surface area than the other regions. 3. Over a period of 20 days there
was little indication of movement of the externally absorbed nutrients into the
internal organs. In this period, very little loss of amino acid radioactivity was
noted. The amino acids became progressively less soluable in alcohol, suggesting
that they were incorporated into the structural proteins of the organism. 4.
Glucose radioactivity declined progressively over the 20-day period. As observed
in Asterias, this decline occurred almost exclusively in the portion of absorbed
glucose that remained alcohol-soluble. This fraction was possibly used as an
energy source while the insoluble fraction became incorporated into more inert
elements. 5. A number of the specimens of Henricia appeared to pump up and absorb
the glucose medium into their digestive organs. This was interpreted as a form of
feeding behavior possibly initiated by the relatively high concentration of
glucose used. The much less concentrated amino acid medium failed to initiate
such a reaction. 6. It is concluded that nutrition in starfish is probably a dual
process involving both a continuous epidermal absorption of dissolved exogenous
materials for the benefit primarily of the superficial tissues, and intermittent
oral feeding to satisfy the more general needs of the entire organism and
especially of the internal organs.
PMID- 29332437
TI - ENVIRONMENTALLY CONTROLLED INDUCTION OF PRIMARY MALE GONOCHORISTS FROM EGGS OF
THE SELF-FERTILIZING HERMAPHRODITIC FISH, RIVULUS MARMORATUS POEY.
AB - 1. Rivulus marmoratus is the only known hermaphroditic fish species naturally
self-fertilizing. Tissue grafts between wild-caught fish and their uniparental
laboratory descendants give the autograft reaction, indicating propagation by
selfing in the wild also. Only hermaphrodites have been found in the wild
locally, although selfing through more than 10 uniparental laboratory generations
yielded a few primary male gonochorists, under 5% in contrast to over 95% that
were hermaphrodites. Females seem to be non-existent. 2. Two series of
experiments were undertaken to identify a possible environmental factor able to
cause a deviation to the male phenotype during sex differentiation, on the
working hypothesis that low male incidence in clones composed otherwise of
hermaphrodites indicated a lability in the sex-determining mechanism through
which the genotype normally produces the hermaphrodite phenotype. 3. Individuals
of two clones, each in its own jar throughout life, were exposed to the eight
combinations of bright or dim light, sea water or fresh water, high or low
temperature (Experimental Series One). Exposure was from not later than the 3/4
blastoderm stage until sexual maturity at high temperature or five months post
hatching at low. 4. Over seven times the number of males previously encountered
were obtained all but one from low-temperature treatments. Male production was
correlated with low-temperature rearing despite alternative light intensities and
salinities and structural-functional abnormalities (prolapsed oviduct, pharyngeal
hyperplasia, kyphosis) peculiar to different dim-light, salinity-temperature
combinations, and partly attributable to hormonal derangements. Mortalities were
high enough to present the formal dilemma of a differential male induction versus
hermaphrodite mortality at low temperature and vice versa at high, but this
dilemma was resolved by Experimental Series Two. 5. The Experimental Series One
fish were monitored daily up to 1,376 days post-hatching, by which time almost
60% of the hermaphrodites had changed to functional secondary male gonochorists,
the rest dying or killed as hermaphrodites, some each year. Primary males remain
unchanged except for senile degeneration. Secondary males arise mostly late in
laboratory-prolonged life, by involution of the ovarian component of the
ovotestes with further evolution of the testicular component, the caudal ocellus
fading or vanishing as they become orange like the primary males. 6. In
Experimental Series Two, mortalities were low and the structural-functional
abnormalities were absent. All individuals were kept at the same intermediate
salinity and light intensity: Group A, at moderate temperature throughout to
maturity; Group B, at the same temperature through hatching, at low temperature
the first five months post-hatching, thereafter at the moderate temperature;
Group C, at the moderate temperature up to stages from optic vesicle formation to
outset of blood circulation, then at low temperature through eclosion and for
five months post-eclosion. Group-C embryos being cut from their chorions to
minimize deaths from hatching failure. 7. The Group-A eggs yielded 100%
hermaphrodites, the Group-B eggs, 92% hermaphrodites and 8% deaths, the Group-C
eggs, 72% males, 18% hermaphrodites, and 10% deaths. Exposure to low temperature
from as late as outset of blood circulation produced males. 8. The uniqueness of
the present experiments and results, exclusion of alternative explanations,
significance of the temperature effect per se, and the implications of these
findings for the interpretation of intersexuality in fishes are discussed at
length.
PMID- 29332438
TI - NORTHERN PACIFIC GIGANTIONE (ISOPODA).
AB - 1. Eight species of Gigantione have now been described. One was from the north
Atlantic, one from the Indian Ocean, two from the south Pacific, and four from
the north Pacific. Of these last, G. pratti and G. hawaiiensis are new species.
The hosts of the different species have all been in separate genera, with the
exception of those for G. giardi and G. hawaiiensis, both of which were in
Xantho. 2. Dr. Shiino is carrying out an intensive investigation of epicarids in
the Japanese archipelago, and the writer is in the process of preparing a
monograph covering the Epicaridea of the northern Pacific (except for those areas
and forms near Japan). Therefore, it should be expected that many new species and
possibly genera will be found in the Pacific as collecting continues.
PMID- 29332439
TI - THE GROWTH AND ACTIVITY OF THE CORPORA ALLATA IN THE LARVAL FIREBRAT, THERMOBIA
DOMESTICA (PACKARD) (THYSANURA, LEPISMATIDAE).
AB - 1. The integument of the firebrat, Thermobia domestica, lacks scales until the
molt from the third to the fourth larval stage, but retains them in all
subsequent instars. 2. Implantation experiments confirm earlier findings that the
scaleless integument of first stage larvae will develop scales prematurely when
implanted into a molting adult, implying that the formation of scales is
humorally determined. 3. The number of cells in the corpora allata increases
progressively throughout the life of the firebrat, and the relationship between
the number of allatal cells and the weight of the firebrat is expressed by the
regression: y = 10.61 + 1.94x, where y = the number of cells in each corpus
allatum and x = the weight of the insect in mg. The regression does not intersect
the origin. 4. The size of nuclei in the corpus allatum remains constant
throughout life, but the volume of cytoplasm can alter. The minimal cytoplasmic
volume coincides with the deposition of the first scale-bearing cuticle. The
amount of cytoplasm then increases abruptly, the level continuing to rise slowly
throughout the rest of larval life. A further increase may occur in mated
females. 5. The juvenile hormone activity of the corpora allata, when assayed on
pupae of the silkmoth Antheraea polyphemus, correlates with the volume of
cytoplasm in the gland, and is minimal in the third stage. 6. The activity of the
corpora allata is influenced by the intake of food, specifically protein. 7.
Dedifferentiation of the epidermis is prevented by the pattern of growth in the
corpus allatum, which indicates that the secretory potential of the gland,
expressed as the volume of allatal cytoplasm per milligram body weight, is
greater during the first through third instars than at any later stage, and by
the inactivation of juvenile hormone during the molting cycle.
PMID- 29332440
TI - SURFACE AREA RESPIRATION DURING THE HATCHING OF ENCYSTED EMBRYOS OF THE BRINE
SHRIMP, ARTEMIA SALINA.
AB - Oxygen consumption of Artemia salina was measured during development in 0.5 M
NaCl at 25 degrees C. A pattern is seen in which the rate of oxygen consumption
increases rapidly within the first few hours after hydration, remains constant
for a time, and then increases rapidly again while most of the embryos are
emerging. This pattern is dependent upon surface area of the developing embryo.
During emergence, the surface area of the embryo increases 172% over the surface
area of the encysted embryo. During the same development period, oxygen uptake
increases by almost the same factor.
PMID- 29332441
TI - THE RELATIONSHIP OF TEMPERATURE TO THE LARVAL DEVELOPMENT OF NASSARIUS OBSOLETUS
(GASTROPODA).
AB - 1. Development of the embryos of Nassarius obsoletus within egg capsules is
regulated by sea-water temperature. An increase in the time required between
spawning and the emergence of veliger larvae is slight between 28 degrees and 20
degrees C., about 0.25 day for each degree decrease in temperature. Between 20
degrees and 16.5 degrees C., the corresponding increase was 2 days per degree
decrease in temperature. At 11.5 degrees C., development was not completed and
larvae did not emerge from their egg capsules after nine weeks. However, a large
proportion of these embryos survived and developed normally through metamorphosis
when placed at room temperature. 2. The growth rate of planktonic veliger larvae
of N. obsoletus was greatest at approximately 25 degrees C. The lowest
temperature at which the development to metamorphosis was completed was at 16
degrees to 17 degrees C. There was a 46% inhibition in the growth rate of
larvae between the optimum temperature and the minimum temperature at which
development is completed. 3. The larval life of N. obsoletus veligers may be
divided into two stages. The first of these, the "developmental period," is one
during which rapid growth and morphological development occur. This is followed
by the "delay period" characterized by a gradual decrease in growth rate. Reduced
temperature may influence the rate of growth and consequently the length of the
"developmental period." The termination of the "developmental period" comes with
the "creeping-swimming stage." The duration of the "delay period" may be quite
variable and is determined by the availability of a favorable sediment for
settlement.
PMID- 29332442
TI - THE MORPHOLOGY, LIFE-HISTORY, AND SYSTEMATIC RELATIONS OF THE DIGENETIC
TREMATODE, UNISERIALIS BREVISERIALIS SP. NOV., (NOTOCOTYLIDAE), A PARASITE OF THE
BURSA FABRICIUS OF BIRDS.
AB - Imbricata-type cercariae from Hydrobia salsa, a brackish-water, prosobranch snail
taken near Woods Hole, Massachusetts, emerge shortly before noon, are
photopositive and encyst after swimming for a few minutes to three to four hours.
Metacercariae were fed to chicks and domestic ducklings and developed to mature
worms after about two weeks in the bursae Fabricii of these birds. Adult and
larval stages are described and figured. The worms belong in the family
Notocotylidae and are assigned to the genus, Uniserialis Beverley-Burton, 1958.
Systematic problems of genera in the family are discussed.
PMID- 29332444
TI - THE EFFECT OF LIGHT ON THE SPAWNING OF CIONA INTESTINALIS.
AB - 1. The spawning of Ciona intestinalis with respect to light was studied, using
both white light and monochromatic light. 2. A one-hour dark-adaption period
followed by exposure to light resulted in spawning by 66.6% of the 884 animals
tested. 3. Spawning occurs an average of 27.3 minutes after the onset of
illumination. 4. Illumination need not be continuous until spawning occurs; the
animals spawn when returned to the dark after a short illumination period,
provided they have received enough energy. 5. The action spectrum for spawning
suggests cytochrome c as a chromophore.
PMID- 29332443
TI - GENETIC AND DEVELOPMENTAL STUDIES ON BOTRYLLUS SCHLOSSERI.
AB - 1. Properties of Botryllus schlosseri which give it outstanding promise for
studies in developmental genetics are reviewed. 2. Laboratory culture procedures,
in vitro fertilization, and a method for raising embryos in vitro are described.
Controlled successions of complete life cycles can now be achieved in any
laboratory. 3. Experiments involving colony fusion, subsequent vascular budding,
and the analysis of color patterns in resultant systems suggest that cells of the
simple vessel walls govern the morphology of the regenerated zooids. 4. Results
of some preliminary genetic crosses are reported.
PMID- 29332445
TI - Stylet angulation of 70 degrees reduces the time to intubation with the
GlideScope(r): A prospective randomised trial.
AB - Objective The GlideScope(r) videolaryngoscope provides a good view of the
glottis. However, directing and inserting an endotracheal tube is sometimes
difficult during intubation with the GlideScope(r). In this study, we compared
two GlideScope(r) stylet angulations (90 degrees vs. 70 degrees ) in terms of
the time to intubation. Methods In total, 162 patients scheduled for elective
surgery under general anaesthesia were randomly assigned to one of two groups. In
the 90 group ( n = 79), a 90 degrees stylet was used. In the 70 group ( n = 78),
a 70 degrees stylet was used. The time to intubation was recorded. The number of
intubation attempts was assessed. Results The time to intubation was
significantly shorter in the 70 than 90 group [26.0 (23.0-32.0) vs. 37.0 (30.0
43.0) s, respectively]. The first-time intubation success rate was significantly
higher and the number of failed intubations was significantly lower in the 70
than 90 group (100% vs. 87% and 0% vs. 6%, respectively). Conclusions This
investigation suggests that a 70 degrees angle stylet is superior to a 90
degrees angle stylet for GlideScope(r) intubation. Trial Registration
Clinicaltrials.gov Identifier: NCT02547064.
PMID- 29332446
TI - Lung Cancer Complicated With Asymptomatic Pulmonary Embolism: Clinical Analysis
of 84 Patients.
AB - BACKGROUND AND OBJECTIVE: Pulmonary embolism is potentially life-threatening in
patients with lung cancer, but the clinical studies on patients with lung cancer
having asymptomatic pulmonary embolism were barely reported. METHODS: Clinical
data of patients with lung cancer were obtained from the Department of
Respiratory and Critical Care Medicine of Tianjin Chest Hospital during July 2012
and June 2015 and were reviewed retrospectively. A total of 28 patients with lung
cancer having pulmonary embolism (LP group) were enrolled, and another 56 cases
with lung cancer alone (LC group) were enrolled as controls. RESULTS: Seventeen
(60.7%) of 28 patients in the LP group developed adenocarcinoma, which was more
frequent than that in the LC group ( P < .01); the LP group displayed lower
counts of hemoglobin and albumin than the LC group ( P < .05); the counts of
leukocyte (white blood cell) and d-dimer of patients in the LP group were also
higher than those in the LC group ( P < .05). The high-incidence period of
pulmonary embolism among 17 asymptomatic cases in the LP group was 3.6 months
postdiagnosis (95% confidence interval, 3.2-4.0), showing a significant
difference with that of other 11 patients with symptomatic pulmonary embolism,
which was 10.5 months (95% confidence interval, 8.88-12.12; P < .01). Survival
analysis displayed that median survival time of patients with asymptomatic
pulmonary embolism was 7.2 months (95% confidence interval, 5.86-8.56), while
that of symptomatic pulmonary embolism was 2.8 months (95% confidence interval,
2.48-3.12). Log-rank examination showed that survival time of asymptomatic
pulmonary embolism group was statistically longer than that of symptomatic
pulmonary embolism group. CONCLUSION: Lung adenocarcinoma, chemotherapy,
hyperleukocytosis, and d-dimer increment were the risk factors for lung cancer
combined with asymptomatic pulmonary embolism.
PMID- 29332447
TI - A Projection Quality-Driven Tube Current Modulation Method in Cone-Beam CT for
IGRT: Proof of Concept.
AB - PURPOSE: To develop a projection quality-driven tube current modulation method in
cone-beam computed tomography for image-guided radiotherapy based on the prior
attenuation information obtained by the planning computed tomography and then
evaluate its effect on a reduction in the imaging dose. MATERIALS AND METHODS:
The QCKV-1 phantom with different thicknesses (0-400 mm) of solid water upon it
was used to simulate different attenuation (MU). Projections were acquired with a
series of tube current-exposure time product (mAs) settings, and a 2-dimensional
contrast to noise ratio was analyzed for each projection to create a lookup table
of mAs versus 2-dimensional contrast to noise ratio, MU. Before a patient
underwent computed tomography, the maximum attenuation [Formula: see text] within
the 95% range of each projection angle (theta) was estimated according to the
planning computed tomography images. Then, a desired 2-dimensional contrast to
noise ratio value was selected, and the mAs setting at theta was calculated with
the lookup table of mAs versus 2-dimensional contrast to noise ratio,[Formula:
see text]. Three-dimensional cone-beam computed tomography images were
reconstructed using the projections acquired with the selected mAs. The imaging
dose was evaluated with a polymethyl methacrylate dosimetry phantom in terms of
volume computed tomography dose index. Image quality was analyzed using a Catphan
503 phantom with an oval body annulus and a pelvis phantom. RESULTS: For the
Catphan 503 phantom, the cone-beam computed tomography image obtained by the
projection quality-driven tube current modulation method had a similar quality to
that of conventional cone-beam computed tomography . However, the proposed method
could reduce the imaging dose by 16% to 33% to achieve an equivalent contrast to
noise ratio value. For the pelvis phantom, the structural similarity index was
0.992 with a dose reduction of 39.7% for the projection quality-driven tube
current modulation method. CONCLUSIONS: The proposed method could reduce the
additional dose to the patient while not degrading the image quality for cone
beam computed tomography. The projection quality-driven tube current modulation
method could be especially beneficial to patients who undergo cone-beam computed
tomography frequently during a treatment course.
PMID- 29332448
TI - Helical Therapy is Safe for Lung Stereotactic Body Radiation Therapy Despite
Limitations in Achieving Sharp Dose Gradients.
AB - PURPOSE: We observed that many of our helical therapy lung stereotactic body
radiation therapy plans did not meet the Radiation Therapy Oncology Group (RTOG)
recommended R50% (volume of 50% of the prescription dose/planning target volume),
which characterizes the steepness of dose fall off. We hypothesized that despite
not meeting R50%, helical therapy lung stereotactic body radiation therapy plans
would confer similar local control and minimal side effects as previously
reported using nonhelical treatment platforms. MATERIALS AND METHODS: We report a
retrospective review of all consecutive patients treated off-protocol with
stereotactic body radiation therapy for peripheral lung lesions from 2008 to 2013
utilizing helical therapy. Seventy-four patients (81 lesions and 79 plans) were
treated with doses ranging from 48 to 60 Gy in 3 to 5 fractions prescribed to the
edge of the planning target volume. RESULTS: Forty-eight (61%) plans had major
deviation from R50%. Only 1 (<1%) plan had a major deviation from the R100%. All
plans had > 95% planning target volume coverage by prescription dose, 7(8.6%)
plans with 121% to 133% maximum dose, and lung V20 Gy <10% in 70 (89%) plans.
With a median follow-up of 4.7 years (95% confidence interval: 4.1-5.3), local
control for all patients at 1, 2, and 5 years was 94.6%, 83.4%, and 74%,
respectively. For patients with primary stage I-II lung cancer (n = 46), the 1,
2, and 5-year local control: 97.2%, 94.2%, and 86.9%; RC: 97.6%, 82.5%, and
69.5%; and DM: 3%, 16%, and 33.4%, respectively. Patients treated for lung
metastases (n = 26) had worse local control at 1, 2, and 5 years: 94.4%, 69.3%,
and 55.5%, respectively. Side effects were rare with 2 (3%) patients reporting
chest wall pain and 6 (8%) patients experiencing radiation pneumonitis, including
1 patient who had grade 5 radiation pneumonitis. CONCLUSIONS: Helical therapy
delivers a safe and effective lung stereotactic body radiation therapy plan,
despite not being able to meet RTOG's recommended R50 conformality constraint.
PMID- 29332449
TI - Mir-452-3p: A Potential Tumor Promoter That Targets the CPEB3/EGFR Axis in Human
Hepatocellular Carcinoma.
AB - PURPOSE: We proposed to investigate the effects of miR-452-3p on the
proliferation and mobility of hepatocellular carcinoma (HCC) cells by targeting
cytoplasmic polyadenylation element binding protein 3/estimated glomerular
filtration rate (CPEB3/EGFR) axis. METHODS: Quantitative real-time polymerase
chain reaction (qRT-PCR) was used to detect miR-452-3p expression in 84 pairs of
HCC tissues and adjacent tissues. Luciferase reporter assay was employed to
examine the relationship between miR-452-3p and CPEB3. Microculture tetrazolium
(MTT) assay, colony formation assay, flow cytometry detection, wound healing
assay, and transwell assay were used to detect cell proliferation, cycle arrest,
apoptosis, and mobility, respectively, in HCC, HepG2, and Huh-7. Western blot was
used to detect protein expression levels in EGFR signaling pathway. Kaplan-Meier
survival analysis was conducted to analyze the correlation between the miR-452-3p
and CPEB3 expression levels and the survival of patients with HCC. RESULTS: MiRNA
452-3p was found significantly upregulated in 84 human HCC sample tissues and
cells in comparison with adjacent tissues and normal liver epithelial cells ( P <
.01). Luciferase reporter assay demonstrated that CPEB3 was a direct target of
miR-452-3p. Overexpression of miR-452-3p promoted cell proliferation and mobility
and suppressed apoptosis. MiR-452-3p enhanced EGFR and phosphorylated AKT (pAKT)
expression but inhibited p21 expression level. CONCLUSION: MiR-452-3p promoted
HCC cell proliferation and mobility by directly targeting the CPEB3/EGFR axis.
PMID- 29332451
TI - PSCA rs1045531 Polymorphism and the Risk of Prostate Cancer in a Chinese
Population Undergoing Prostate Biopsy.
AB - BACKGROUND AND PURPOSE: This study explored the association between a single
nucleotide polymorphism of prostate stem cell antigen and prostate cancer in
Chinese patients undergoing prostate biopsy. MATERIALS AND METHODS: DNA from 416
patients undergoing prostate biopsy was typed for the prostate stem cell antigen
rs1045531 single-nucleotide polymorphism. The frequency of the rs1045531
polymorphism in patients with prostate cancer and in patients with benign
prostatic hyperplasia was compared. Associations between the polymorphism and the
risk of prostate cancer, prostate special antigen, Gleason score, and clinical
stage were analyzed. RESULTS: Statistically significant differences in the
distribution of the rs1045531 genotypes and alleles were found between prostate
cancer and benign prostatic hyperplasia in patients undergoing prostate biopsy (
P = .035 and .046, respectively). We found that the rs1045531 AC genotype was
significantly associated with a high risk of prostate cancer in the heterozygote
model (AC vs CC; odds ratio = 2.383, 95% confidence interval: 1.198-4.741, chi2 =
6.229, P = .013) and the dominant model (AA/AC vs CC; odds ratio = 2.169, 95%
confidence interval: 1.112-4.229, chi2 = 5.228, P = .022). However,
susceptibility of prostate cancer was decreased in the homozygote model (AA vs
CC; odds ratio = 0.828, 95% confidence interval: 0.143-4.805, P = .601). When
considering clinical factors, the rs1045531 showed an association with prostate
special antigen of 10 ng/mL or greater, a Gleason score of 7 or greater, and a
size of T2 or greater. CONCLUSION: Men with the rs1045531 AC genotype of prostate
stem cell antigen were at higher risk of prostate cancer in Chinese patients
undergoing prostate biopsy.
PMID- 29332452
TI - The DNMT3B -579G>T Polymorphism Is Significantly Associated With the Risk of
Gastric Cancer but not Lung Cancer in Chinese Population.
AB - The -149C>T and -579G>T, 2 single nucleotide polymorphisms in de novo
methyltransferase 3B gene promoter, have been previously reported to potentially
alter the promoter activity and to influence cancer risk. However, the results
from previous studies remain conflicting rather than conclusive. In view of this,
we conducted a case-control study and then a meta-analysis to examine the
association between these 2 single-nucleotide polymorphisms with risk of lung and
gastric cancer in Chinese population. The genotyping was performed by polymerase
chain reaction-restriction fragment length polymorphism and confirmed by
sequencing. In this case-control study, no significant association with lung or
gastric cancer risk was observed for -149C>T, while -579G>T was significantly
correlated with the risk of gastric cancer but not lung cancer. Moreover,
haplotype analysis showed that haplotype -149T/-579 T, which carried the risk
579 T allele, significantly increased the susceptibility to gastric cancer.
However, none of the haplotypes was associated with the risk of lung cancer. The
following meta-analysis involved only Chinese population and further confirmed
the significant association of -579G>T with gastric cancer but not lung cancer
and suggested no significant association between -149C>T and risk of lung or
gastric cancer. Collectively, DNMT3B -579G>T polymorphism is associated with
gastric cancer risk in Chinese population, and the -579G>T may be used as a
genetic biomarker to predict the risk of gastric cancer in Chinese population.
PMID- 29332450
TI - Identification and Comparison of Differentiation-Related Proteins in
Hepatocellular Carcinoma Tissues by Proteomics.
AB - Histological differentiation is a major pathological criterion indicating the
risk of tumor invasion and metastasis in patients with hepatocellular carcinoma.
The degree of tumor differentiation is controlled by a complex interacting
network of associated proteins. The principal aim of the present study is to
identify the possible differentiation-related proteins which may be used for
early diagnosis and more effective therapies. We compared poorly differentiated
and well-differentiated hepatocellular carcinoma tissues by using 2-dimensional
gel electrophoresis and matrix-assisted laser desorption ionization time-of
flight mass spectrometry. Among the 11 identified protein spots, 6 were found to
be upregulated in poorly differentiated hepatocellular carcinoma tissues and 5
were correspondingly downregulated. Immunohistochemistry was performed on 106
hepatocellular carcinoma tissues to confirm the results of the proteomic
analysis. By using bioinformatic tools GO and STRING, these proteins were found
to be related to catalytic activity, binding, and antioxidant activity. In
particular, our data suggest that overexpression of peroxiredoxin-2, annexin A2,
and heat shock protein beta-1 was correlated with tumor invasion, metastasis, and
poor prognosis, and therefore, these proteins may serve as potential diagnostic
and therapeutic biomarkers.
PMID- 29332454
TI - Intrafractional Tracking Accuracy of a Transperineal Ultrasound Image Guidance
System for Prostate Radiotherapy.
AB - PURPOSE: The aim of this study is to evaluate the tracking accuracy of a
commercial ultrasound system under relevant treatment conditions and demonstrate
its clinical utility for detecting significant treatment deviations arising from
inadvertent intrafractional target motion. METHODS: A multimodality male pelvic
phantom was used to simulate prostate image-guided radiotherapy with the system
under evaluation. Target motion was simulated by placing the phantom on a motion
platform. The tracking accuracy of the ultrasound system was evaluated using an
independent optical tracking system under the conditions of beam-on, beam-off,
poor image quality with an acoustic shadow introduced, and different phantom
motion cycles. The time delay between the ultrasound-detected and actual phantom
motion was investigated. A clinical case example of prostate treatment is
presented as a demonstration of the utility of the system in practice. RESULTS:
Time delay between the motion phantom and ultrasound tracking system is 223 +/-
45.2 milliseconds including video and optical tracking system frame rates. The
tracking accuracy and precision were better with a longer period. The precision
of ultrasound tracking performance in the axial (superior-inferior) direction was
better than that in the lateral (left-right) direction (root mean square errors
are 0.18 and 0.25 mm, respectively). The accuracy of ultrasound tracking
performance in the lateral direction was better than that in the axial direction
(the mean position errors are 0.23 and 0.45 mm, respectively). Interference by
radiation and image quality do not affect tracking ability significantly.
Further, utilizing the tracking system as part of a clinical study for prostate
treatment further verified the accuracy and clinical appropriateness.
CONCLUSIONS: It is feasible to use transperineal ultrasound daily to monitor
prostate motion during treatment. Our results verify the accuracy and precision
of an ultrasound system under typical external beam treatment conditions and
further demonstrate that the tracking system was able to identify important
prostate shifts in a clinical case.
PMID- 29332453
TI - MRI-Related Geometric Distortions in Stereotactic Radiotherapy Treatment
Planning: Evaluation and Dosimetric Impact.
AB - In view of their superior soft tissue contrast compared to computed tomography,
magnetic resonance images are commonly involved in stereotactic
radiosurgery/radiotherapy applications for target delineation purposes. It is
known, however, that magnetic resonance images are geometrically distorted, thus
deteriorating dose delivery accuracy. The present work focuses on the assessment
of geometric distortion inherent in magnetic resonance images used in
stereotactic radiosurgery/radiotherapy treatment planning and attempts to
quantitively evaluate the consequent impact on dose delivery. The geometric
distortions for 3 clinical magnetic resonance protocols (at both 1.5 and 3.0 T)
used for stereotactic radiosurgery/radiotherapy treatment planning were evaluated
using a recently proposed phantom and methodology. Areas of increased distortion
were identified at the edges of the imaged volume which was comparable to a brain
scan. Although mean absolute distortion did not exceed 0.5 mm on any spatial
axis, maximum detected control point disposition reached 2 mm. In an effort to
establish what could be considered as acceptable geometric uncertainty, highly
conformal plans were utilized to irradiate targets of different diameters (5-50
mm). The targets were mispositioned by 0.5 up to 3 mm, and dose-volume histograms
and plan quality indices clinically used for plan evaluation and acceptance were
derived and used to investigate the effect of geometrical uncertainty
(distortion) on dose delivery accuracy and plan quality. The latter was found to
be strongly dependent on target size. For targets less than 20 mm in diameter, a
spatial disposition of the order of 1 mm could significantly affect (>5%) plan
acceptance/quality indices. For targets with diameter greater than 2 cm, the
corresponding disposition was found greater than 1.5 mm. Overall results of this
work suggest that efficacy of stereotactic radiosurgery/radiotherapy applications
could be compromised in case of very small targets lying distant from the
scanner's isocenter (eg, the periphery of the brain).
PMID- 29332457
TI - REPAIR AND REATTACHMENT IN THE BALANIDAE AS RELATED TO THEIR CEMENTING MECHANISM.
AB - Barnacles, which become partially or totally detached from their substratum in a
natural environment, produce a secondary cement secretion. Laboratory experiments
demonstrate that the secondary cement can successfully reattach the barnacle to a
new substratum. Similar secondary secretion was found at the site of minor
injuries to the barnacle basis. The secondary cement usually has a looser, more
cavernous structure than the primary cement, but both secretions have similar
staining characteristics. Microscope preparations indicate that occasionally
barnacles are capable of developing new secondary cement ducts leading into the
injured or detached areas to secrete secondary cement. In most cases, however,
the existing primary cement duct network is used for the secondary secretion.
This is possible only because most of the once used ducts are not plugged by
hardened cement, in spite of the fact that the cement can harden inside the
ducts. Chemical analysis suggests that the cement is an organic biopolymer and
indications are that the cement hardening is initiated inside the organism. A
unique flushing mechanism seems to be responsible for keeping the cement ducts
open and ready for reuse. A nonhardening flushing fluid forces the still liquid
cement out of the ducts. The cement hardens outside the duct openings sealing the
flushing fluid inside the duct network. In case of detachment or injury. the
cement seal breaks; the flushing fluid drains out leaving the duct open for the
secondary cement secretion. The vesicles in conjunction with the main channel
control the flow of the flushing fluid and the cement. The permeable wall of the
main channel portion inside the vesicle reduces the convection and diffusion
between the vesicle and the main channel, thus bypassing of vesicles and duct
networks not affected by detachment is possible. The wall of the main channel
inside the vesicle is also collapsible, thus acting as checkvalve when the
vesicle is under pressure and allowing the cement to be pumped only into the
ducts toward the secretory orifices.
PMID- 29332459
TI - ABSTRACTS OF PAPERS PRESENTED AT THE MARINE BIOLOGICAL LABORATORY 1970.
PMID- 29332458
TI - THE APPARENT WATER-PERMEABILITY OF CARCINUS MAENAS (CRUSTACEA, BRACHYURA,
PORTUNIDAE) AS A FUNCTION OF SALINITY.
AB - 1. The apparent water-permeability of Carcinus maenas, as measured by D2O influx,
is 2-3 times higher than that of the more euryhaline crab Rhithropanopeus. 2.
Like Rhithropanopeus, Carcinus shows a reduction of water-exchange rate at lower
salinities. The highest hourly water-exchange fraction is in 75% SW (K = 2.73),
the lowest in 30% SW (K = 1.76); values refer to a crab with wet weight of 10 g,
at 18 degrees C. 3. The calculated net diffusional (osmotic) water influx is
adequate to account for the urine production of Carcinus in 50-70% SW, but does
not account for urine production in SW, and only inadequately for the urine
produced in 30-40% SW, and it seems necessary to postulate some isotonic
transport of water.
PMID- 29332456
TI - The Combined Antitumor Effects of 125I Radioactive Particle Implantation and
Cytokine-Induced Killer Cell Therapy on Xenograft Hepatocellular Carcinoma in a
Mouse Model.
AB - The combination of radiotherapy and immunotherapy has shown great promise in
eradicating tumors. For example, 125I radioactive particle implantation and
cytokine-induced killer cell therapies have demonstrated efficacy in treating
hepatocellular carcinoma. However, the mechanism of this combination therapy
remains unknown. In this study, we utilized cytokine-induced killer cells
obtained from human peripheral blood mononuclear cells along with 125I
radioactive particle implantation to treat subcutaneous hepatocellular carcinoma
xenograft tumors in BALB/c nude mice. The effects of combination therapy on tumor
growth, tumor cell apoptosis and proliferation, animal survival, and immune
indexes were then assessed. The results indicated that 125I radioactive particle
implantation combined with cytokine-induced killer cells shows a much greater
antitumor therapeutic effect than either of the therapies alone when compared to
control treatments. Mice treated with a combination of radiotherapy and
immunotherapy displayed significantly reduced tumor growth. 125I radioactive
particle implantation upregulated the expression of major histocompatibility
complex (MHC) class I chain-related gene A in hepatocellular carcinoma cells and
enhanced cytokine-induced killer cell-mediated apoptosis through activation of
caspase-3. Furthermore, cytokine-induced killer cells supplied immune substrates
to induce a strong immune response after 125I radioactive particle implantation
therapy. In conclusion, 125I radioactive particle implantation combined with
cytokine-induced killer cell therapy significantly inhibits the growth of human
hepatocellular carcinoma cells in vivo and improves animal survival times through
mutual promotion of antitumor immunity, presenting a promising therapy for
hepatocellular carcinoma.
PMID- 29332461
TI - FILTRATION OF PARTICLES FROM SUSPENSION BY THE AMERICAN OYSTER CRASSOSTREA
VIRGINICA.
AB - 1. Particle filtration by the oyster Crassostrea virginica was studied in the 1.0
to 12.0 u size range in relation to naturally occurring particles and to
kaolinite suspensions in filtered river water. 2. Oysters were held in troughs of
flowing water under conditions similar to their natural environment. Particle
number and volumes entering and leaving the troughs were enumerated using a
Coulter electronic particle counter. Particle diameter was expressed as that of a
sphere having a volume equal to the particle. 3. Results of the study were
expressed as per cent of total particles removed in various size increments or in
volumes removed over the same size range. 4. Oysters filtered naturally occurring
particles in the 1.0 to 3.0 u range with about one-third the efficiency as larger
particles. Above 3.0 u there was no change in efficiency with increasing particle
size. For kaolinite particles, oysters removed particles in the 1.0 to 2.0 u
range with about half the efficiency as larger particles. Above this size there
was no change. 5. When results are expressed in terms of per cent removal, the
importance of the small sized particles is minimized. In terms of volume,
particles in the 1.0 to 3.0 u range constitute the largest single size fraction
over the 1.0 to 12.0 u range. 6. The consistent presence of an inflection point
at a particle size around 2.0- 3.0 u in the curve for per cent removed vs.
particle size is an indication that the distance between adjacent latero-frontal
cilia is the factor that determines the smallest particle size that can be
completely retained by the oyster gill. 7. Presence of the inflection point is
also interpreted as negating the existence of a mucous sheet over the gills, as
suggested by MacGinitie (1941). 8. Particles in the 1.0 to 3.0 u range may play
an important role in the nutrition of oysters and other lamellibranchs. Their
removal by these organisms may also be an important factor in sedimentary
processes.
PMID- 29332455
TI - DNA Repair Mechanism Gene, XRCC1A ( Arg194Trp) but not XRCC3 ( Thr241Met)
Polymorphism Increased the Risk of Breast Cancer in Premenopausal Females: A Case
Control Study in Northeastern Region of India.
AB - X-ray repair cross complementary group gene is one of the most studied candidate
gene involved in different types of cancers. Studies have shown that X-ray repair
cross complementary genes are significantly associated with increased risk of
breast cancer in females. Moreover, studies have revealed that X-ray repair cross
complementary gene polymorphism significantly varies between and within different
ethnic groups globally. The present case-control study was aimed to investigate
the association of X-ray repair cross complementary 1A (Arg194Trp) and X-ray
repair cross complementary 3 (Thr241Met) polymorphism with the risk of breast
cancer in females from northeastern region of India. The present case-control
study includes histopathologically confirmed and newly diagnosed 464 cases with
breast cancer and 534 apparently healthy neighborhood community controls.
Information on sociodemographic factors and putative risk factors were collected
from each study participant by conducting face-to-face interviews. Genotyping of
X-ray repair cross complementary 1A (Arg194Trp) and X-ray repair cross
complementary 3 (Thr241Met) was carried out by polymerase chain reaction
restriction fragment length polymorphism. For statistical analysis, both
univariate and multivariate logistic regression analyses were performed. We also
performed stratified analysis to find out the association of X-ray repair cross
complementary genes with the risk of breast cancer stratified based on menstrual
status. This study revealed that tryptophan allele (R/W-W/W genotype) in X-ray
repair cross complementary 1A (Arg194Trp) gene significantly increased the risk
of breast cancer (adjusted odds ratio = 1.44, 95% confidence interval = 1.06
1.97, P < .05 for R/W-W/W genotype). Moreover, it was found that tryptophan
allele (W/W genotype) at codon 194 of X-ray repair cross complementary 1A
(Arg194Trp) gene significantly increased the risk of breast cancer in
premenopausal females (crude odds ratio = 1.66, 95% confidence interval = 1.11
2.46, P < .05 for R/W-W/W genotype). The present study did not reveal any
significant association of X-ray repair cross complementary 3 (Thr241Met)
polymorphism with the risk of breast cancer. The present study has explored that
X-ray repair cross complementary 1A (Arg194Trp) gene polymorphism is
significantly associated with the increased risk of breast cancer in
premenopausal females from northeastern region of India which may be beneficial
for prognostic purposes.
PMID- 29332460
TI - ACETYLCHOLINESTERASE ACTIVITY IN ESERINE-TREATED ASCIDIAN EMBRYOS.
AB - 1. The use of specific cholinesterase inhibitors and substrates demonstrated that
the enzyme activity in Ciona intestinalis larvae is an acetylcholinesterase. 2.
Eggs treated with eserine sulfate (an acetylcholinesterase inhibitor) for one
hour prior to fertilization developed into larvae with defective muscular
movements and greatly reduced levels of acetylcholinesterase activity. 3. Two
kinds of experiments show that this reduced enzyme activity was caused by the
retention of eserine and not by inhibition of acetylcholinesterase synthesis.
Homogenates of embryos from eserine-treated eggs inhibit acetylcholinesterase
activity when mixed with homogenates of control embryos. Full enzyme activity in
homogenates of the experimental embryos could be recovered by dialysis.
PMID- 29332462
TI - STUDIES ON THE BIOLUMINESCENCE OF THE MARINE OSTRACOD CRUSTACEAN CYPRIDINA
SERRATA.
AB - 1. The physical appearance and bioluminescence behavior, and light-emitting
reaction of the marine ostracod crustacean, Cypridina serrata, are described. 2.
In the natural environment of the sea, the free-swimming C. serrata appears to
emit almost instantaneously a bright blue luminous cloud when stimulated with
artificial light. 3. The method of light production, consisting of the ejection
of luciferin and luciferase into sea water, and the color of light are similar to
that of C. hilgendorfii. 4. In captivity, C. serrata emits apparent spontaneous
flashes of light, whose duration is approximately 1.5 seconds, with an apparent
latency of 500-800 milliseconds. 5. C. serrata luciferase cannot be distinguished
from C. hilgendorfii luciferase by gel elution chromatography but may be
distinguished immunochemically. 6. The luminescence of C. serrata is due to a
first order reaction, similar to that of C. hilgendorfii. The luciferins and
luciferases of both organisms cross-react to give light. 7. The luminescence of
C. serrata, like C. hilgendorfii, is oxygen dependent. 8. C. serrata luciferin is
similar, if not identical, to C. hilgendorfii luciferin when compared by paper
chromatography.
PMID- 29332463
TI - CHANGES IN MICROTUBULES OF CILIA AND FLAGELLA FOLLOWING NEGATIVE STAINING WITH
PHOSPHOTUNGSTIC ACID.
AB - 1. Variability in the macerating action of 1% aqueous phosphotungstic acid, pH
6.8, is exemplified in microtubules of flatworm and rhynchocoel cilia, from one
grid square to another of the same preparation and within a single grid square.
The central singlets appear to be the most susceptible and are often completely
absent, even in cases where the binding matrix is still present around the
doublets. Maceration usually, but not always, begins at the distal tip of a
cilium and proceeds towards the basal plate; it is evident along the lengths of
doublets as partial or complete loss of one subtubule, as breaks and bends, and
as fraying into the component protofibrils, with disappearance of the white line
marking the wall between the subtubules. 2. Cortical singlet microtubules of a
spermatozoon were thrown into a helical configuration by the action of PTA, while
the flagellar microtubules of the same spermatozoon were unaffected. 3. After
treatment with 1% PTA at pH 8.3, the central singlets of cilia (but not the
doublets) were semi-fused along most of their lengths, and had a beaded
appearance; there were breaks in the doublets but otherwise they appeared to be
unaffected. 4. Ciliary rootlets were rarely seen, but when present had a clear
790 A major repeating pattern and a longitudinal fibrous substructure.
PMID- 29332464
TI - THE ORIGIN, DISTRIBUTION AND FATE OF THE MOLTING FLUID PROTEINS OF THE CECROPIA
SILKWORM.
AB - 1. Molting in insects is always accompanied by the production of a molting fluid
which fills the exuvial space between the new and the old cuticle and digests the
inner layers of the old cuticle. In Hyalophora cecropia, molting fluid is
secreted at the outset of adult development and persists until two days before
eclosion, whereupon it is absorbed. 2. The present report examines the protein
composition of the molting fluid of Cecropia, the origin of the molting fluid
proteins, the relation of these proteins to blood proteins and the exchange of
macromolecules between the molting fluid and the blood. It also examines the
sites of absorption of molting fluid. 3. Disc electrophoresis on acrylamide gels
reveals that the molting fluid of Cecropia contains about fifteen protein bands
which can be resolved at pH 8.6. Some of these protein bands are detected in the
molting fluid at all stages, whereas others appear only at specific times. About
ten of the bands are peculiar to molting fluid and are not detected in the blood.
About five bands are detectable in both blood and molting fluid, but none of
these common bands appears to be a major component of the molting fluid, and only
one is a major blood protein. In contrast, the epidermis contains most of the
major protein bands found in molting fluid but lacks all but one of the major
protein bands present in the blood. 4. Immunological analysis reveals that blood
and molting fluid share five antigens. At least four of these common antigens
also occur in the epidermis which appears to secrete these antigens into both the
molting fluid and the blood. 5. Native and foreign proteins do not penetrate from
the exuvial space into the blood or vice versa. Apparently the epidermis and
cuticle act as a barrier to the exchange of most macromolecules between the blood
and molting fluid. The exuvial space is clearly a separate fluid compartment. 6.
In addition the exuvial space itself is compartmentalized and the fluids in the
compartments do not admix several days before eclosion. 7. Absorption of molting
fluid during the final two days of adult development occurs most readily through
particular regions of the integument. In the abdomen the principal sites of
absorption are pits which represent the points through which tonofibrils make
attachment to the old cuticle. Two days before ecdysis, the attachments between
the tonofibrils and the pupal cuticle rupture, exposing the points of attachment
on the new cuticle. It is through these exposed surfaces that much of the molting
fluid is absorbed. Molting fluid is also absorbed in the head and thorax through
various flexible membranes at the bases of the appendages.
PMID- 29332465
TI - CHANGES IN THE EPIDERMAL HISTOLOGY DURING THE SLOUGHING CYCLE IN THE RAT SNAKE
PTYAS KORROS SCHLEGEL, WITH CORRELATED OBSERVATIONS ON THE THYROID GLAND.
AB - 1. Study of the epidermal histology throughout the sloughing cycle in the snake
Ptyas korros revealed the existence of a well-defined mesos layer and showed that
the alpha-layer is completed in the immediate post-shedding resting-phase. These
observations supplement previous histological studies of the snake epidermis and
further substantiate the essential homology of the epidermal generation in these
forms with similar units in lizards. 2. Thyroid weight is not correlated with
follicular cell height nor with epidermal cell changes throughout the sloughing
cycle. 3. Changes in follicular cell height, indicative of varying levels of
gland activity can be correlated with epidermal changes. The shedding complex and
the outermost portions of the new inner epidermal generation differentiate during
a period of lowest thyroid gland activity: gland activity is highest around
sloughing. 4. These results provide a possible explanation for previous
experimental studies of thyroid-sloughing relations in snakes. The problem of the
difference between snakes and lizards in this context is discussed.
PMID- 29332466
TI - A GENERAL METHOD FOR THE MONOXENIC CULTIVATION OF THE DAPHNIDAE.
AB - Fourteen species of the family Daphnidae have been established under continuous
monoxenic cultivation utilizing Chlamydomonas reinhardii as sole food organism in
a medium consisting of calcium acetate, antibiotics, albumin, trace elements and
the water soluble vitamins, folic acid, B12, calcium pantothenate, choline,
pyridoxal, inositol, thiamin, nicotinamide, riboflavin, biotin and putrescine.
The Daphnidae under cultivation include Daphnia magna, D. pulex, D. galeata
mendotae, D. laevis, D. dubia, D. retrocurva, D. parvula, D. ambigua, D. catawba,
Moina macrocopa Scapholeberis mucronata, Simocephalus serrulatus, Ceriodaphnia
reticulata, and C. quadrangula. The requirements for vitamins for some species
are more complex than for others. The complete medium is superior for all but
Scapholeberis mucronata and markedly increases the lifespan and fertility of
Moina macrocopa.
PMID- 29332467
TI - Is Hippocampal Avoidance During Whole-Brain Radiotherapy Risky for Patients With
Small-Cell Lung Cancer? Hippocampal Metastasis Rate and Associated Risk Factors.
AB - OBJECTIVES: Hippocampal avoidance during whole-brain radiotherapy is performed to
prevent neural stem cell injury causing neurocognitive dysfunction. Nevertheless,
the estimated risk of metastases in hippocampal avoidance area in small-cell lung
cancer is unknown. The current study aimed to characterize the metastatic
distribution within the brain relative to the hippocampus, estimate the incidence
of hippocampal metastasis in patients with small-cell lung cancer, and identify
clinical and radiographic variables that may be associated with the risk of
hippocampal avoidance area metastasis. MATERIALS AND METHODS: Patients with small
cell lung cancer treated with therapeutic whole-brain radiotherapy between
January 2010 and December 2015 were reviewed. T1-weighted, postcontrast axial
magnetic resonance images obtained just before therapeutic cranial irradiation
were retrieved and reviewed for each patient. The hippocampal avoidance area was
defined as hippocampus and 5-mm ring area adjacent to the hippocampus to account
for necessary dose falloff between the hippocampus and the whole-brain planning
target volume. Metastatic lesions within hippocampal avoidance area were defined
as hippocampal metastasis. Hippocampal metastasis rate and characteristics of
patients with hippocampal metastasis were analyzed and compared to patients
without hippocampal metastasis. RESULTS: Fifty-four patients evaluated with
cranial magnetic resonance imaging were enrolled. Hippocampal metastasis rate was
32% (17 patients). A total of 4.4% of all metastases involved the hippocampal
avoidance area. The most common location was frontal lobe. Being younger than 65
years of age was found to be an independent risk factor for HM (odds ratio: 4.8,
95% confidence interval: 1-23.2, P = .049). The number of brain metastases was
significantly higher in patients with hippocampal metastasis ( P = .027), and
hippocampal metastasis rate was also higher in patients having larger hippocampus
( P = .026) and larger brain volumes ( P = .02). CONCLUSION: Hippocampal
metastasis might be more common in small-cell lung cancer. Reducing the dose to
the hippocampus by hippocampal avoiding whole-brain radiotherapy plan in small
cell lung cancer may be risky for the development of HM compared with other
malignant solid tumors.
PMID- 29332469
TI - Balance Regularity Among Former High School Football Players With or Without a
History of Concussion.
AB - CONTEXT: Subclinical postural-control changes may persist beyond the point when
athletes are considered clinically recovered postconcussion. OBJECTIVE: To
compare postural-control performance between former high school football players
with or without a history of concussion using linear and nonlinear metrics.
DESIGN: Case-control study. SETTING: Clinical research laboratory. PATIENTS
OR OTHER PARTICIPANTS: A total of 11 former high school football players (age
range, 45-60 years) with 2 or more concussions and 11 age- and height-matched
former high school football players without a history of concussion. No
participant had college or professional football experience. MAIN OUTCOME
MEASURE(S): Participants completed the Sensory Organization Test. We compared
postural control (linear: equilibrium scores; nonlinear: sample and multiscale
entropy) between groups using a 2 * 3 analysis of variance across conditions 4 to
6 (4: eyes open, sway-referenced platform; 5: eyes closed, sway-referenced
platform; 6: eyes open, sway-referenced surround and platform). RESULTS: We
observed a group-by-condition interaction effect for medial-lateral sample
entropy ( F2,40 = 3.26, P = .049, etap2 = 0.140). Participants with a history of
concussion presented with more regular medial-lateral sample entropy values (0.90
+/- 0.41) for condition 5 than participants without a history of concussion (1.30
+/- 0.35; mean difference = -0.40; 95% confidence interval [CI] = -0.74, -0.06;
t20 = -2.48, P = .02), but conditions 4 (mean difference = -0.11; 95% CI: -0.37,
0.15; t20 = -0.86, P = .40) and 6 (mean difference = -0.25; 95% CI: -0.55, 0.06;
t20 = -1.66, P = .11) did not differ between groups. CONCLUSIONS:
Postconcussion deficits, detected using nonlinear metrics, may persist long after
injury resolution. Subclinical concussion deficits may persist for years beyond
clinical concussion recovery.
PMID- 29332468
TI - Local Radiotherapy Affects Drug Pharmacokinetics-Exploration of a Neglected but
Significant Uncertainty of Cancer Therapy.
AB - PURPOSE: Concurrent chemoradiation therapy is the mainstay of treatment for many
types of malignancies. However, concurrent chemoradiation therapy is associated
with a greater number of systemic adverse effects than radiotherapy or
chemotherapy alone. SUMMARY: Pharmacokinetics is the study of a drug and/or its
metabolite kinetics in the body, including absorption, distribution, metabolism,
and elimination. The incidences of adverse effects are markedly higher in
patients who receive concurrent chemoradiation therapy than in those who receive
either radiotherapy or chemotherapy alone. This phenomenon implies that
irradiation affects the pharmacokinetics of cytotoxic agents, namely the
radiotherapy-pharmacokinetic phenomenon. Experimental animal studies have shown
that local irradiation affects the systemic pharmacokinetics of 5-fluorouracil
and cisplatin at both low dose (simulating generous dose distributed to normal
tissues) and daily practice dose (mimicking therapeutic dose to target volumes).
These effects are significant in the circulation of blood and lymphatic system as
well as in the hepatobiliary excretion. Furthermore, recent studies have
demonstrated that matrix metalloproteinase-8 plays an important role in the
radiotherapy-pharmacokinetic phenomenon. CONCLUSION: In the present review, we
provide a general overview of the radiotherapy-pharmacokinetic phenomenon and
discuss the possible mechanisms governing the phenomenon.
PMID- 29332470
TI - A School-Based Neuromuscular Training Program and Sport-Related Injury Incidence:
A Prospective Randomized Controlled Clinical Trial.
AB - CONTEXT: An estimated 40 million school-aged children (age range = 5-18 years)
participate annually in sports in the United States, generating approximately 4
million sport-related injuries and requiring 2.6 million emergency department
visits at a cost of nearly $2 billion. OBJECTIVE: To determine the effects of a
school-based neuromuscular training (NMT) program on sport-related injury
incidence across 3 sports at the high school and middle school levels, focusing
particularly on knee and ankle injuries. DESIGN: Randomized controlled clinical
trial. SETTING: A total of 5 middle schools and 4 high schools in a single
county public school district. PATIENTS OR OTHER PARTICIPANTS: A total of 474
girls (222 middle school, 252 high school; age = 14.0 +/- 1.7 years, height =
161.0 +/- 8.1 cm, mass = 55.4 +/- 12.2 kg) were cluster randomized to an NMT
(CORE; n = 259 athletes) or sham (SHAM; n = 215 athletes) intervention group by
team within each sport (basketball, soccer, and volleyball). INTERVENTION(S):
The CORE intervention consisted of exercises focused on the trunk and lower
extremity, whereas the SHAM protocol consisted of resisted running using elastic
bands. Each intervention was implemented at the start of the season and continued
until the last competition. An athletic trainer evaluated athletes weekly for
sport-related injuries. The coach recorded each athlete-exposure (AE), which was
defined as 1 athlete participating in 1 coach-directed session (game or
practice). MAIN OUTCOME MEASURE(S): Injury rates were calculated overall, by
sport, and by competition level. We also calculated rates of specific knee and
ankle injuries. A mixed-model approach was used to account for multiple injuries
per athlete. RESULTS: Overall, the CORE group reported 107 injuries (rate =
5.34 injuries/1000 AEs), and the SHAM group reported 134 injuries (rate = 8.54
injuries/1000 AEs; F1,578 = 18.65, P < .001). Basketball (rate = 4.99
injuries/1000 AEs) and volleyball (rate = 5.74 injuries/1000 AEs) athletes in the
CORE group demonstrated lower injury incidences than basketball (rate = 7.72
injuries/1000 AEs) and volleyball (rate = 11.63 injuries/1000 AEs; F1,275 = 9.46,
P = .002 and F1,149 = 11.36, P = .001, respectively) athletes in the SHAM group.
The CORE intervention appeared to have a greater protective effect on knee
injuries at the middle school level (knee-injury incidence rate = 4.16
injuries/1000 AEs) than the SHAM intervention (knee-injury incidence rate = 7.04
injuries/1000 AEs; F1,261 = 5.36, P = .02). We did not observe differences
between groups for ankle injuries ( F1,578 = 1.02, P = .31). CONCLUSIONS:
Participation in an NMT intervention program resulted in a reduced injury
incidence relative to participation in a SHAM intervention. This protective
benefit of NMT was demonstrated at both the high school and middle school levels.
PMID- 29332471
TI - Fatal Exertional Heat Stroke and American Football Players: The Need for Regional
Heat-Safety Guidelines.
AB - CONTEXT: Weather-based activity modification in athletics is an important way
to minimize heat illnesses. However, many commonly used heat-safety guidelines
include a uniform set of heat-stress thresholds that do not account for
geographic differences in acclimatization. OBJECTIVE: To determine if heat
related fatalities among American football players occurred on days with
unusually stressful weather conditions based on the local climate and to assess
the need for regional heat-safety guidelines. DESIGN: Cross-sectional study.
SETTING: Data from incidents of fatal exertional heat stroke (EHS) in American
football players were obtained from the National Center for Catastrophic Sport
Injury Research and the Korey Stringer Institute. PATIENTS OR OTHER PARTICIPANTS:
Sixty-one American football players at all levels of competition with fatal
EHSs from 1980 to 2014. MAIN OUTCOME MEASURE(S): We used the wet bulb globe
temperature (WBGT) and a z-score WBGT standardized to local climate conditions
from 1991 to 2010 to assess the absolute and relative magnitudes of heat stress,
respectively. RESULTS: We observed a poleward decrease in exposure WBGTs during
fatal EHSs. In milder climates, 80% of cases occurred at above-average WBGTs, and
50% occurred at WBGTs greater than 1 standard deviation from the long-term mean;
however, in hotter climates, half of the cases occurred at near average or below
average WBGTs. CONCLUSIONS: The combination of lower exposure WBGTs and
frequent extreme climatic values in milder climates during fatal EHSs indicates
the need for regional activity-modification guidelines with lower, climatically
appropriate weather-based thresholds. Established activity-modification
guidelines, such as those from the American College of Sports Medicine, work well
in the hotter climates, such as the southern United States, where hot and humid
weather conditions are common.
PMID- 29332472
TI - Statistical Primer for Athletic Trainers: The Essentials of Understanding
Measures of Reliability and Minimal Important Change.
AB - OBJECTIVE: To describe the concepts of measurement reliability and minimal
important change. BACKGROUND: All measurements have some magnitude of error.
Because clinical practice involves measurement, clinicians need to understand
measurement reliability. The reliability of an instrument is integral in
determining if a change in patient status is meaningful. DESCRIPTION:
Measurement reliability is the extent to which a test result is consistent and
free of error. Three perspectives of reliability-relative reliability, systematic
bias, and absolute reliability-are often reported. However, absolute reliability
statistics, such as the minimal detectable difference, are most relevant to
clinicians because they provide an expected error estimate. The minimal important
difference is the smallest change in a treatment outcome that the patient would
identify as important. RECOMMENDATIONS: Clinicians should use absolute
reliability characteristics, preferably the minimal detectable difference, to
determine the extent of error around a patient's measurement. The minimal
detectable difference, coupled with an appropriately estimated minimal important
difference, can assist the practitioner in identifying clinically meaningful
changes in patients.
PMID- 29332474
TI - THE MARINE BIOLOGICAL LABORATORY.
PMID- 29332473
TI - THE NUTRITION OF PARANEMERTES PEREGRINA (RHYNCHOCOELA: HOPLONEMERTEA). II.
OBSERVATIONS ON THE STRUCTURE OF THE GUT AND PROBOSCIS, SITE AND SEQUENCE OF
DIGESTION, AND FOOD RESERVES.
AB - 1. Digestion in the hoplonemertean Paranemertes peregrina is achieved by a
combination of extra- and intracellular processes. The extracellular phase,
effected in an acidic medium, involves endopeptidases secreted by the
gastrodermal columnar cells, and other, as yet unidentified, substances
discharged from the intestinal gland cells. The semi-digested food is then
phagocytosed and digestion completed intracellularly by peptidases, carbohydrases
and lipases acting in harmony. Intracellular digestion is initially acid and then
alkaline, with acid and alkaline phosphatases associated with the appropriate
phases. 2. Nereids used as food are caught by the proboscis, and immobilized by
secretions produced by the posterior proboscis gland cells. These secretions are
pumped into the body of the prey via wounds caused by the central stylet. The
nature of these secretions has not definitely been established, but they may
contain the toxin anabaseine. 3. The anterior proboscis secretions are concerned
with aiding the grip of the proboscis papillae and possibly with initiating the
denaturation of the prey epidermis. 4. Acid secretions are produced by the
foregut via a mechanism that does not involve carbonic anhydrase. 5. Other sites
of enzymic activity have been reported, and where possible suggestions made as to
their probable roles. 6. Fat forms the principal food reserve, with major
deposits being stored in the gastrodermal columnar cells, but some glycogen is
stored in a variety of body tissues.
PMID- 29332475
TI - THE EVALUATION OF THE "CALLIPHORA TEST" AS AN ASSAY FOR ECDYSONE.
AB - 1. The effect of ligation on pupariation in the front or hind parts of larvae of
four species of flies, Calliphora erythrocephala, Phormia regina, Sarcophaga
bullata, and S. argyrostoma was investigated. Ligation causes effects of delay or
inhibition of pupariation which are very differently expressed in the four
species. A large proportion of pre- or postcritically ligated specimens of P.
regina and S. bullata altogether fail to pupariate in the anterior part. This
makes these species unsuitable test subjects for the pupariation test for
ecdysone. 2. Test abdomens of C. erythrocephala required significantly less
ecdysone for a given pupariation effect when also injected with a CNS-extract.
Tanning was also considerably accelerated in this case. 3. The value of the
pupariation unit of ecdysone is influenced by a number of factors, such as age at
the time of ligation, the waiting period between ligation and injection, the
dilution effect of the solvent, and the simultaneous action of a neurohormone.
The requirements for natural ecdysone in normal larvae at the time of pupariation
are probably substantially lower than the values which have been determined by
others with test abdomens and the use of synthetic ecdysones. 4. In confirmation
of older data, and contrary to recent claims, tanning was induced in test
abdomens of the larvae of C. erythrocephala, P. regina, and S. argyrostoma by the
injection of hemolymph from pupariating larvae. Calliphora blood induced tanning
in specimens of S. argyrostoma, and vice versa. The conclusions are drawn that
differences between the different species in the action of ecdysone are of a
quantitative rather than qualitative nature.
PMID- 29332476
TI - CALCIFICATION IN ECHINODERMS: EFFECTS OF TEMPERATURE AND DIAMOX ON INCORPORATION
OF CALCIUM-45 IN VITRO BY REGENERATING SPINES OF STRONGYLOCENTROTUS PURPURATUS.
AB - 1. Calcification during regeneration of experimentally fractured spines of the
sea urchin, Strongylocentrotus purpuratus (Stimpson), was studied quantitatively
under different conditions with calcium-45 as a tracer. 2. Fractured spines
rapidly incorporated 45Ca in vivo or in vitro after a lag period of about two
days. The lag period is attributed to wound healing and reorganization of tissue
at the site of fracture. 3. Additional experiments were conducted while
calcification was in progress by allowing fractured spines to regenerate for four
days in vivo followed by incubation in 45Ca in vivo or in vitro up to 24 hours.
In these experiments incorporation of the label was nearly linear with time and
no significant difference was observed in the rate of uptake of 45Ca between
regenerating spines incubated in vivo and those from the same urchin incubated
simultaneously in vitro. 4. Incorporation of 45Ca in vitro was directly
proportional to temperature between 4.7 degrees and 20 degrees C, at which a
maximum occurred. A temperature of 26 degrees C appeared to be lethal and little
incorporation of 45Ca took place. Values of Q10 and the energy of activation
varied inversely with temperature, with overall means of 2.72 and 15,504 calories
per mole, respectively, between 4.7 degrees and 20 degrees C. 5. Diamox
(acetazolamide) at concentrations from 10-3 to 10-6 M, inhibited incorporation of
45Ca in vitro by 50% to 61%. It is inferred from these results that carbonic
anhydrase is involved in calcification of regenerating spines of S. purpuratus.
PMID- 29332477
TI - A COMPARATIVE STUDY OF THE CEMENT GLANDS IN SOME BALANID BARNACLES (CIRRIPEDIA,
BALANIDAE).
AB - 1. The histological characteristics of the cement gland cells of barnacles have
been compared in B. nubilis, B. psittacus, B. eburneus, B. balanoides and B.
amphitrite. 2. In B. balanoides, the cement gland cells show a very simple
composition; they are situated at the base of the animal and the secretion
appears scattered throughout the cytoplasm. The cement apparatus of B. amphitrite
and B. eburneus looks like that of B. tintinnabulum, but in B. psittacus and B.
nubilis the cement gland cells appear more complex. 3. The extrusion of the
cement secretion is brought about by muscle fibers that pass through the
connective tissue, and in B. psittacus and B. nubilis by elastic fibers around
the secondary and principal canal systems.
PMID- 29332478
TI - LARVAL DEVELOPMENT OF PAGURUS LONGICARPUS SAY REARED IN THE LABORATORY, I.
DESCRIPTION OF LARVAL INSTARS.
PMID- 29332479
TI - LIFE CYCLE OF THE HYDROMEDUSA PHIALIDIUM GREGARIUM (A. AGASSIZ, 1862) IN THE
LABORATORY.
AB - 1. A method was described by which hydroid colonies, each on a microscopic slide,
were raised from individual planulae of the leptomedusa known as Phialidium
gregarium. 2. Growth and behavior of approximately 30 cultures were observed and
quantitated through nearly 2 months. Cultures produced gonangia and medusae 3-7
weeks after fertilization of the egg. 3. Gonosome development was always preceded
by a burst of hydroid development 5-9 days previously. This burst appeared to be
initiated entirely by an abundant food supply (brine shrimp). 4. Medusae were
liberated 4-5 days after gonangia first appeared. From the growth rate of medusae
under the less than optimal laboratory conditions, it was estimated that sexual
maturity may be reached in approximately 3 weeks. The lifespan of the medusae
probably does not exceed 3 months. 5. A small number of cultures wintered in an
open cage in the sea. At the end of November they were found in a greatly reduced
state and possessed only a very few, very small hydranths. At the end of March
they were in the early phases of vigorous trophosomal growth and the gonosome had
just begun to flourish. 6. From the behavior of clonal colonies in the
laboratory, the hypothesis was derived that the swarms of mature medusae in
nature are the direct result of a "bloom" in zooplankton which occurred 5-7 weeks
previously and stimulated first hydroid development and in consequence the
formation of gonangia. 7. Morphological characteristics of the hydroid colonies
were described and their variability under laboratory conditions recorded and
discussed. It was shown that many taxonomic features such as size, branching,
number of tentacles and annulations depend quantitatively on the age of the
individual colony, its state of nutrition and on genetic factors. 8. The hydroid
belongs to the genus Clytia (Lamouroux, 1816). A careful comparison was made with
species of the genus as described for the Puget Sound region and California. It
was concluded that none of these delineates unambiguously the morphological
features of this hydroid. A tentative name for the hydroid was assigned according
to priority principles as Clytia gregaria. It was suggested that Phialidium
gregarium may be the most appropriate name for the species in both its phases.
PMID- 29332480
TI - NATURAL AND SYNTHETIC MATERIALS WITH INSECT HORMONE ACTIVITY. 5. SPECIFIC
JUVENILE HORMONE EFFECTS IN ALIPHATIC SESQUITERPENES.
AB - The juvenile hormone activity of ethyl or methyl esters of aliphatic
sesquiterpenic acids with 0 to 4 double bonds was tested on 8 species of insects
belonging to 5 families of Hemiptera and Coleoptera. Special attention was paid
to the addition of hydrogen chloride or epoxide groups on or across the double
bonds. Certain chemical changes in the molecule appear to cause a general
increase of the activity in all species studied. These are: the presence of 2,3
unsaturation conjugated with the carboxyl group; the trans stereochemical
position of the C-3 methyl; an introduction of 10,11 epoxide or hydrochloride;
and esterification with ethyl rather than with methyl. There are also chemical
changes which lead to genus- or family-specific variations in juvenile hormone
activity. With increasing amount of unsaturation the activity either remains
almost unaffected (pyrrhocorid bugs) or increases (pentatomid bugs) or decreases
considerably (tenebrionid and dermestid beetles). The addition of hydrogen
chloride or epoxide to the 6,7 double bond causes enormous increase in the
activity in the Pyrrhocoridae and Lygaeidae, no considerable change in the
Pentatomidae, and great decreases in the beetles and Lepidoptera.
PMID- 29332481
TI - THE NUTRITION OF PARANEMERTES PEREGRINA (RHYNCHOCOELA: HOPLONEMERTEA). I. STUDIES
ON FOOD AND FEEDING BEHAVIOR.
AB - 1. Paranemertes peregrina, an abundant hoplonemertean in rocky and muddy
intertidal habitats of Washington, feeds on polychaetes during low tide periods.
2. Feeding by Paranemertes involves three steps. The first stage is a recoil of
the Paranemertes' head upon contact with a prey. Contact must be made with the
prey; Paranemertes does not find prey by distance chemoreception. The proboscis
is everted and wraps around the prey in step two. The prey is temporarily
paralyzed or is killed. In step three the prey is ingested by means of sucking
motions from muscles around the mouth. Defecation occurs from 12 to 33 hours
after feeding. 3. Specimens of Paranemertes ate mainly nereid polychaetes at the
three study areas where nereids were available. At the fourth study area the
nemerteans ate a wider variety of polychaetes. Experiments to test food
preference showed that specimens of Paranemertes from all study areas strongly
preferred nereids to members of other polychaete families. 4. Nereid polychaetes
have a swimming escape response from Paranemertes.
PMID- 29332482
TI - EFFECTS OF SUPERABUNDANT OXYGEN ON THERMAL TOLERANCE OF GOLDFISH.
AB - A hypothesis may be made out that the respiratory/circulatory, and possibly the
oxygen transport, systems are importantly involved in thermal death of goldfish.
Experiments showed that at two distinct levels of temperature acclimation,
superabundant oxygen in the water could produce a definite improvement either in
time of survival at a fixed lethal temperature or in lethal temperature reached
as a result of heating. Despite this positive effect of high oxygen a clear cut
failure of oxygen, in excess of about 5 atmospheres (partial pressure), to
produce further improvement in thermal tolerance suggests the failure of some
critical system directly affected by temperature. The experiments, while
revealing nothing of the detailed mechanisms involved, certainly do not
invalidate the hypothesis proposed, and open a way to further investigation.
PMID- 29332483
TI - ENVIRONMENTAL TEMPERATURE AND THYROID ACTIVITY IN THE LIZARD, SCELOPORUS
OCCIDENTALIS.
AB - The relationship between temperature and the hypophyseal-thyroidal axis in
Sceloporus occidentalis has been investigated by a study of radioiodine
incorporation by the thyroid in intact animals, and animals with the pars
distalis removed, kept at temperatures of 15 degrees , 21 degrees , 30 degrees
and 38 degrees C. Over the range of 21 to 38 degrees C there was no evidence of
any significant temperature-related change in the normal and experimental
animals, although the thyroid activity was reduced after the operation. At 15
degrees C the thyroid functioning was significantly inhibited and there was no
difference between the normal and experimental animals. It is suggested that the
role of temperature in thyroid activation is a permissive one. Data for I131
incorporation in hypophysectomized animals receiving TSH therapy offers a
possible explanation for the different patterns of thyroidal I131 accumulation
observed in different forms of lizards.
PMID- 29332484
TI - EMERSION OF THE AMPHIBIOUS CHILEAN CLINGFISH, SICYASES SANGUINEUS.
AB - The amphibious clingfish Sicyases sanguineus attaches by means of its ventral
sucker to vertical surfaces of large exposed rocks splashed by the cool and heavy
surf of Chile and southern Peru. Although adult and halfgrown fish tolerate
diluted seawater and can survive at least a few hours in warm and stagnant water,
they seldom, if ever, occur in isolated tidal pools, bays, or estuaries. Factor
analysis indicates that clingfish come out of the water more abundantly during
periods of calm and often turn head-down. They avoid drying rocks outside the
spray zone and emerge onto higher rocks as the water level rises. Adult fish come
out of the water more abundantly in remote areas relatively undisturbed by
civilization. Insolation apparently does not directly alter the abundance of
clingfish, which act so as to minimize evaporative water loss and overheating.
Terrestrial fish breathe air held in their gill cavities, probably through their
gills. As they come out of the water, fish gulp air, then stop all opercular
movements to seal their cavities, and often turn head-down. This positioning may
facilitate airbreathing by easing the expulsion of spent gas upward through the
watery gill cavities and by shading an area of delicate respiratory epithelium
under the chin. The volume percentage oxygen in gas expelled into a viscous
solution of resin in sea water decreased regularly for about 12 minutes in a
young fish, about 30 minutes in a halfgrown fish, and about one hour in an adult
before these fish renewed their branchial gas. Although a concomitant increase in
percentage carbon dioxide indicated that the branchial gas contributed to
respiration, rates of oxygen uptake calculated from modal volumes of expelled gas
were only about 12-30% of the fish's total long-term rate in air as determined by
other investigators. As in other airbreathing fishes, however, cutaneous
respiration may supplement branchial respiration, which fills the total need only
when the metabolic rate falls. Exposure of their head apparently stimulates
clingfish to gulp, so that atmospheric air, rather than aquatic hypoxia, is their
primary stimulation to airbreathing. Fish in stagnating water do not necessarily
emerge and occasionally remain under water until they suffocate. Like other
airbreathing fishes, clingfish appear insensitive to relatively large proportions
of carbon dioxide in their branchial gas. And even with their opercles closed and
their ventral mouths pressed against the substrate, clingfish in the field should
easily eliminate excess carbon dioxide through their wet skin. Vargas and Concha
(1957a) emphasized the ontogenesis of terrestriality in clingfish from erratic
young to well-regulated adult: modification of gill surface to minimize clumping,
control of aerial oxygen uptake, and greater composure on land. The present study
indicates that exposure of an anteroventral respiratory membrane, assumption of a
head-down position, improvement of gulping technique, control and slowing of
ventilation, and greater efficiency of exchange between branchial gas and blood
also contribute critically to the maturing fish's increasing independence of
aquatic life.
PMID- 29332486
TI - PSPB Editorial Philosophy.
PMID- 29332485
TI - Relationship between neutrophil/lymphocyte ratio and epicardial fat tissue
thickness in patients with newly diagnosed hypertension.
AB - Objective Epicardial fat tissue thickness (EFT) and the neutrophil/lymphocyte
ratio (NLR) are associated with atherosclerosis. Few studies have focused on the
relationship between these parameters in patients with newly diagnosed
hypertension. In this study, we examined the relationship between EFT and the NLR
in patients with newly diagnosed hypertension detected by 24-hour ambulatory
blood pressure monitoring (ABPM). Methods Eighty consecutive patients without
chronic illness who were diagnosed with hypertension according to ABPM results
and 80 otherwise healthy subjects were enrolled in the study. EFT of each
participant was measured echocardiographically. The C-reactive protein (CRP)
concentration and NLR were measured from venous blood samples. Results The 24
hour average systolic blood pressure was significantly higher in the hypertension
group than in the control group (143+/-17 vs. 117+/-7 mmHg, respectively). There
were no significant differences in age, sex, or body mass index between the two
groups. EFT, the NLR, and the CRP concentration were significantly higher in the
hypertension group than control group. Additionally, a significantly positive
correlation between EFT and the NLR was found in both the control group and
hypertension group. Conclusion A higher EFT and NLR were detected in patients
with newly diagnosed hypertension than in healthy subjects.
PMID- 29332487
TI - The Prototypical Majority Effect Under Social Influence.
AB - Majority views are reported with greater confidence and fluency than minority
views, with the difference increasing with majority size. This Prototypical
Majority Effect (PME) was attributed generally to conformity pressure, but Koriat
et al. showed that it can arise from the processes underlying decision and
confidence independent of social influence. Here we examined the PME under
conditions that differ in social influence. In Experiment 1, a robust PME emerged
in the absence of information about the majority views, but the provision sof
that information increased the choice of the majority view and magnified the PME.
In Experiment 2, a PME emerged in a minority-biased condition that misled
participants to believe that the majority view was the minority view, but the PME
was stronger in a majority-biased condition. The results were discussed in terms
of a dual-process view: The PME observed under social influence may contain
externally driven and internally driven components.
PMID- 29332489
TI - Thermoacoustic Lensing in Ultrasound Imaging of Nonechogenic Tissue During High
intensity Focused Ultrasound Exposure.
AB - We develop a ray-tracing theory to describe the effects of thermoacoustic lensing
during high-intensity focused ultrasound (HIFU) on ultrasound images of
reflectors lying distal to the HIFU focal region and discuss the application of
thermal lensing effects to dose monitoring in HIFU therapy. By analyzing the
effects of thermal and geometric delays of acoustic rays passing through a region
of tissue undergoing localized heating, we show how the shape of a reflector
distal to the heated region can be predicted and present experimental
measurements in good agreement with the model. We also apply the model in reverse
to estimate the thermal profile of a heated region based on a measured change in
the shape of a distal reflector during HIFU delivery. As an example, we apply
this technique to the measurements of thermal diffusion in porcine fat. An
interesting aspect of the technique is that it can be applied to measure
temperature in nonechogenic tissues as long as there is an observable reflector
in the ultrasound images that is located distal to the region of localized
heating.
PMID- 29332488
TI - Role of the hippocampal 5-HT1A receptor-mediated cAMP/PKA signalling pathway in
sevoflurane-induced cognitivedysfunction in aged rats.
AB - Objective This study aimed to evaluate the role of the hippocampal 5
hydroxytryptamine-1A (5-HT1A)-mediated cyclic adenosine monophosphate/protein
kinase A (cAMP/PKA) signalling pathway in sevoflurane-induced cognitive
dysfunction in aged rats. Methods Sixty 18-month-old Sprague-Dawley rats were
divided into the control (n = 30) and experimental (Sev, n = 30) groups. The
experimental group inhaled 50% air/oxygen mixture (2 L/min) and 2% sevoflurane
for 4 hours. The control group inhaled 50% air/oxygen mixture (2 L/min) for 4
hours. The Morris water maze test was performed The mRNA expression of 5-HT1A
receptor, and cAMP PKA, cAMP response element-binding protein (CREB), and
phosphorylated CREB (p-CREB) protein expression were determined. Results The
escape latency and swimming distance were greater, and the number of crossings of
the platform location and time spent in the platform quadrant were less in the
Sev group compared with the control group. cAMP, PKA, CREB, and p-CREB protein
expression was downregulated in the Sev group 1 day after anaesthesia compared
with the control group. Hippocampal 5-HT1A receptor mRNA expression was higher 7
days after anaesthesia compared with the control group. Conclusion Sevoflurane
induced cognitive dysfunction in aged rats may be related to inhibited expression
of the hippocampal 5-HT1A receptor-mediated cAMP/PKA signalling pathway.
PMID- 29332490
TI - The Oppression of Latina Mothers: Experiences of Exploitation, Violence,
Marginalization, Cultural Imperialism, and Powerlessness in Their Everyday Lives.
AB - Despite Latinos being the largest growing population in the United States,
research has not examined the impact of social structures on the well-being of
Latina immigrants; negative social discourse and restrictive laws exacerbate
inequality and discrimination in this population. Through combined
inductive/deductive analysis of in-depth semistructured interviews, we examined
immigrant Mexican mothers' ( N = 32) descriptions of oppression in the United
States. All five forms of oppression, described in Young's oppression framework
are evident: exploitation, violence, marginalization, cultural imperialism, and
powerlessness. Discrimination places a high burden on Latinas due to the
intersection of forms of oppression and nondominant identities.
PMID- 29332491
TI - Relationship (A)Symmetries and Violence: Comparing Intimates and NonPartners.
AB - Violence between social equals differs in character from violence between persons
in asymmetrical relationships. Specifically, issues of contention motivating
violence vary by the relative status of opponents, such that violence over
symbolic issues is more common between symmetrical than asymmetrical opponents.
Recent studies have substantiated these predictions in nonpartner relationships.
Using data from interviews of incarcerated women, this study explores how
intimate partner violence compares with violence between nonpartner opponents. We
find that intimate partner violence is more likely to involve symbolic issues
compared with violence between all kinds of nonpartner opponents. Consequently,
intimate partnerships might be viewed as hypersymmetrical.
PMID- 29332492
TI - Safety and efficacy of photoselective vaporization of the prostate using the 180
W GreenLight XPS laser system in patients taking oral anticoagulants.
AB - Objective To evaluate the safety and efficacy of the 180-W GreenLight XPS laser
system for the treatment of benign prostatic hyperplasia in patients taking oral
anticoagulants. Methods All consecutive patients admitted for lower urinary tract
symptoms associated with benign prostatic hyperplasia from November 2012 to
October 2016 and who underwent photoselective vaporization of the prostate with
the 180-W GreenLight XPS laser were included in the study. The perioperative
outcomes examined were the operating time, laser time, energy usage, and duration
of postoperative catheterization. Functional parameters (International Prostate
Symptom Score, maximum urinary flow rate, and post-void residual urine volume),
prostate volume, and serum prostate-specific antigen concentration were examined
at baseline and 3 months. Perioperative complications, if any, were noted.
Results All functional parameters (International Prostate Symptom Score, maximum
urinary flow rate, and post-void residual urine volume) significantly improved
from baseline to 3 months. A small number of patients experienced at least one
minor adverse event. There was no difference in the rate of adverse events
between patients who were and were not taking anticoagulants. Conclusions
Photoselective vaporization with a 180-W laser is an efficacious and safe
treatment for benign prostatic hyperplasia, even in patients taking anticoagulant
medications.
PMID- 29332493
TI - College Campus Sexual Assault: The Contribution of Peers' Proabuse Informational
Support and Attachments to Abusive Peers.
AB - Since the mid-1980s, researchers across the United States have uncovered high
rates of sexual assault among female college students. However, to advance a
better understanding of this gendered type of victimization, and to both prevent
and control this problem, the research community needs to identify its major
correlates. One that is consistently uncovered in North American campus survey
work is negative peer support, especially that provided by male peers. Yet, some
earlier studies have found that mixed-sex negative peer support, too, contributes
to campus sexual assault. Using recent data from the Campus Quality of Life
Survey conducted at a large residential school in the South Atlantic region of
the United States, the main objectives of this article are to examine the role of
mixed-sex negative peer support in campus sexual assault and to identify the
groups of women most at risk of having friends who offer such support.
PMID- 29332494
TI - An Evaluation of Adolescent and Young Adult (Re)Victimization Experiences:
Problematic Substance Use and Negative Consequences.
AB - We investigated substance use and negative consequences in women who experienced
an initial sexual assault (SA) in high school and subsequently in college. More
than 650 participants completed questionnaires assessing substance
use/consequences, SA history, and posttraumatic stress disorder (PTSD)
symptomology. Revictimized women reported differential substance use/consequences
relative to controls underscoring the need to conceptualize adolescence as a key
developmental period with a unique pathway to a subsequent SA, especially in
association with substance use. We propose that prevention interventions should
begin no later than ninth grade to limit the risk for an initial experience of SA
and any consequential substance use and abuse.
PMID- 29332495
TI - Comparing Violent Victimization Experiences of Male and Female College-Attending
Emerging Adults.
AB - Despite increased attention to college student victimization, gaps remain. In
particular, relatively little is known about violence against males and females
outside sexual and intimate partner violence. This study uses data from the
National Crime Victimization Survey to compare male and female students' violent
victimization overall as well as relational and sexual violence. Findings reveal
gendered differences and similarities. Results have implications for policies to
prevent violence and support victims. Implications for victim services are
particularly relevant given the critical developmental period for college
students learning coping skills that shape their adult lives and addressing harms
resulting from violent victimization.
PMID- 29332496
TI - Double Jeopardy: Insurance, Animal Harm, and Domestic Violence.
AB - Although the role of companion animals within the dynamic of domestic violence
(DV) is increasingly recognized, the overlap of animal harm and insurance
discrimination for victims/survivors of DV has not been considered. Prompted by a
case study presented in a National Link Coalition LINK-Letter, this research note
examines "Pet Insurance" policies available in Australia and whether
nonaccidental injury caused by an intimate partner would be covered. We discuss
the implications of exclusion criteria for victims/survivors of DV, shelters
providing places for animals within a DV dynamic, and, more broadly, for cross-
or mandatory-reporting (of animal harm) initiatives.
PMID- 29332498
TI - An Updated Assessment of Personal Protective Order Statutes in the United States:
Have Statutes Become More Progressive in the Past Decade?
AB - The Personal Protection Order (PPO) is one civil intervention all states provide
to victims of domestic violence; however, each state varies widely in who can
access PPOs, what protections are included in PPOs, and how they are enforced.
Given the many changes to state PPO statutes over the last decade, this research
replicates and updates DeJong and Burgess-Proctor's research on PPOs' victim
friendliness (using states' 2003 PPO statutes) by examining states' 2014 PPO
statutes. Findings suggest that states have become more victim-friendly with most
states ranking in the highest category of victim-friendliness. Implications for
policy and practice are discussed.
PMID- 29332497
TI - Dosimetric Analysis of Microscopic Disease in SBRT for Lung Cancers.
AB - OBJECTIVE: The objective of this study is to theoretically and experimentally
evaluate the dosimetry in the microscopic disease regions surrounding the tumor
under stereotactic body radiation therapy of lung cancer. METHODS: For
simplicity, the tumor was considered moving along 1 dimension with a periodic
function. The probability distribution function of the tumor position was
generated according to the motion pattern and was used to estimate the delivered
dose in the microscopic disease region. An experimental measurement was conducted
to validate both the estimated dose with a probability function and the
calculated dose from 4-dimensional computed tomography data using a dynamic
thorax phantom. Four tumor motion patterns were simulated with cos4(x) and
sin(x), each with 2 different amplitudes: 10 mm and 5 mm. A 7-field conformal
plan was created for treatment delivery. Both films (EBT2) and optically
stimulated luminescence detectors were inserted in and around the target of the
phantom to measure the delivered doses. Dose differences were evaluated using
gamma analysis with 3%/3 mm. RESULTS: The average gamma index between measured
doses using film and calculated doses using average intensity projection
simulation computed tomography was 80.8% +/- 0.9%. In contrast, between measured
doses using film and calculated doses accumulated from 10 sets of 4-dimensional
computed tomography data, it was 98.7% +/- 0.6%. The measured doses using
optically stimulated luminescence detectors matched very well (within 5% of the
measurement uncertainty) with the theoretically calculated doses using
probability distribution function at the corresponding position. Respiratory
movement caused inadvertent irradiation exposure, with 70% to 80% of the dose
line wrapped around the 10 mm region outside the target. CONCLUSION: The use of
static dose calculation in the treatment planning system could substantially
underestimate the actual delivered dose in the microscopic disease region for a
moving target. The margin for microscopic disease may be substantially reduced or
even eliminated for lung stereotactic body radiation therapy.
PMID- 29332499
TI - Examination of an in vitro methodology to evaluate the biomechanical performance
of nucleus augmentation in axial compression.
AB - Intervertebral disc degeneration is one of the leading causes of back pain, but
treatment options remain limited. Recently, there have been advances in the
development of biomaterials for nucleus augmentation; however, the testing of
such materials preclinically has proved challenging. The aim of this study was to
develop methods for fabricating and testing bone-disc-bone specimens in vitro for
examining the performance of nucleus augmentation procedures. Control, nucleotomy
and treated intervertebral disc specimens were fabricated and tested under static
load. The nucleus was removed from nucleotomy specimens using a trans-endplate
approach with a bone plug used to restore bony integrity. Specimen-specific
finite element models were developed to elucidate the reasons for the variations
observed between control specimens. Although the computational models predicted a
statistically significant difference between the healthy and nucleotomy groups,
the differences found experimentally were not significantly different. This is
likely due to variations in the material properties, hydration and level of
annular collapse. The deformation of the bone was also found to be non
negligible. The study provides a framework for the development of testing
protocols for nucleus augmentation materials and highlights the need to control
disc hydration and the length of bone retained to reduce inter-specimen
variability.
PMID- 29332500
TI - Microstructure and mechanical properties of porous titanium structures fabricated
by electron beam melting for cranial implants.
AB - The traditional methods of metallic bone implants are often dense and suffer from
adverse reactions, biomechanical mismatch and lack of adequate space for new bone
tissue to grow into the implant. The objective of this study is to evaluate the
customized porous cranial implant with mechanical properties closer to that of
bone and to improve the aesthetic outcome in cranial surgery with precision
fitting for a better quality of life. Two custom cranial implants (bulk and
porous) are digitally designed based on the Digital Imaging and Communications in
Medicine files and fabricated using additive manufacturing. Initially, the
defective skull model and the implant were fabricated using fused deposition
modeling for the purpose of dimensional validation. Subsequently, the implant was
fabricated using titanium alloy (Ti6Al4V extra low interstitial) by electron beam
melting technology. The electron beam melting-produced body diagonal node
structure incorporated in cranial implant was evaluated based on its mechanical
strength and structural characterization. The results show that the electron beam
melting-produced porous cranial implants provide the necessary framework for the
bone cells to grow into the pores and mimic the architecture and mechanical
properties closer to the region of implantation. Scanning electron microscope and
micro-computed tomography scanning confirm that the produced porous implants have
a highly regular pattern of porous structure with a fully interconnected network
channel without any internal defect and voids. The physical properties of the
titanium porous structure, containing the compressive strength of 61.5 MPa and
modulus of elasticity being 1.20 GPa, represent a promising means of reducing
stiffness and stress-shielding effect on the surrounding bone. This study reveals
that the use of porous structure in cranial reconstruction satisfies the need of
lighter implants with an adequate mechanical strength and structural
characteristics, thus restoring better functionality and aesthetic outcomes for
the patients.
PMID- 29332501
TI - "Plates and Dishes Smash; Married Couples Clash": Cultural and Social Barriers to
Help-Seeking Among Women Domestic Violence Survivors in Kyrgyzstan.
AB - This article develops a grounded theory of help-seeking to investigate the social
and cultural determinants of help-seeking among Kyrgyz women who have experienced
domestic violence. Results indicate that cultural traditions and social norms
most notably the social construction of marriage, the shame associated with
divorce, and the status of daughters-in-law in Kyrgyz society-are used to justify
domestic violence and prevent victims from seeking help. The proposed theory and
results suggest that scholars, policymakers, and front-line contacts must
emphasize dispelling myths, misconceptions, and traditional beliefs about gender
and marriage to break the abusive dynamics and provide professional help.
PMID- 29332502
TI - Associations Between Home Death and the Use and Type of Care at Home.
AB - Despite wishes for and benefits of home deaths, a discrepancy between preferred
and actual location of death persists. Provision of home care may be an effective
policy response to support home deaths. Using the population-based mortality
follow-back study conducted in Nova Scotia, we investigated the associations
between home death and formal care at home and between home death and the type of
formal care at home. We found (1) the use of formal care at home at the end of
life was associated with home death and (2) the use of formal home support
services at home was associated with home death among those whose symptoms were
well managed.
PMID- 29332503
TI - "They Said on the Death Certificate...But Really What I Think Happened":
Characterizing Cause of Death in VA Medical Centers.
AB - Cause of death information is a vital resource for family and public health, yet
significant issues persist regarding its determination, documentation and
communication. In this study, we aim to characterize cause of death attribution
process from the perspective of next-of-kin of Veterans who died in Veterans
Affairs (VA) Medical Centers. Using a semi-structured guide, we explored next-of
kin's experiences of the Veteran's terminal hospitalization and conducted a
content analysis of interview texts. In over two-third of cases next-of-kin's
understanding was not consistent with their recollection of physicians'
determination of cause of death. Discrepancies between official cause of death
and lay understanding engendered confusion and distress. Findings have relevance
for shaping the context of post-death patient/family-centered clinical practice
and serve as a means for improving efficacy of cause of death communication and
reducing potential for misunderstandings.
PMID- 29332504
TI - Changes in Distress Measured by the Distress Thermometer as Reported by Patients
in Home Palliative Care in Germany.
AB - AIM: To identify changes in distress as reported by patients in a home palliative
care program over a 2-week period. METHODS: Prospective study in West Germany
with consecutive patients cared for at home by a palliative care specialty team.
Exclusion criteria were patients under 18 years of age, mentally or physically
not able to complete the assessment questionnaires, or unable to comprehend
German language. Distress was measured using the distress thermometer (DT);
sociodemographic and medical data were collected from the patients' records.
RESULTS: One hundred three participated in the study (response rate of 69%) and
39 participants completed DT at 2-week follow-up (T1; response rate = 38%; mean
age = 67; female = 54.4%; married = 67%; living home with relatives = 60.2%;
oncological condition = 91.3%; Karnofsky performance status [KPS] 0-40 = 18.9%,
KPS 50-70 = 70.3%, KPS >80 = 10.8%). The mean DT score at the first visit (T0)
was 5.9 (2.3), with 82.1% of the participants scoring DT >=5. At the 2-week
follow-up (T1), mean DT score was 5.0 (2.0), with 64.1% scoring DT >=5, showing a
statistically significant difference between T0 and T1. Comparing the single
scores at T0 and T1 of each participant, the difference in DT scores was -0.9
(2.27). CONCLUSION: The DT is a useful tool for screening severity and changes in
psychological distress as well as sources of distress. The DT detected change in
self-reported distress within a short treatment period, indicating success or
failure of the palliative care treatment approaches.
PMID- 29332505
TI - Building a Novel Health Curriculum for Survivors of Intimate Partner Violence
Residing at a Transitional Housing Program.
AB - We used a community-based participatory research approach to develop, implement,
and evaluate one of the first health curricula for female intimate partner
violence (IPV) survivors residing at a transitional housing program. The
curriculum comprised 12 workshops that were developed based on the survivors'
experiences, needs, and interests. Evaluation participants included 20 of the 37
women who attended at least one workshop, 12 workshop facilitators, and two
housing center staff. Participants found the curriculum to be engaging,
interactive, and helpful in building a supportive community. Suggestions for
curricular improvement as well as opportunities for further research and
curricular development are discussed.
PMID- 29332506
TI - Rape Crimes: Are Victims' Acute Psychological Distress and Perceived Social
Support Associated With Police Case Decision and Victim Willingness to
Participate in the Investigation?
AB - This study examined level of acute psychological distress and perceived social
support in 64 victims of rape and the association with police case decisions and
victims' willingness to participate in the investigation. The results of
independent-sample t tests revealed that victims' unwillingness to participate in
the investigation was significantly associated with a higher level of
psychological distress in the acute phase following the assault. The results
suggest that victims of rape who disengage with the police investigation may do
so because of a high level of acute psychological distress. Clinical implications
are discussed.
PMID- 29332507
TI - An Evaluation of the Impacts of Changing Firearms Legislation on Australian
Female Firearm Homicide Victimization Rates.
AB - Reducing lethal violence against women requires comprehensive measures addressing
individual, social, economic, cultural, and situational factors. Regarding
situational factors, access to weapons-and firearm access in particular-has
received notable research attention. However, most study comes from the United
States of America, and findings may not apply elsewhere. The current study
examines whether changing gun laws in Australia affected female firearm homicide
victimization. Female firearm homicide victimization may have been affected;
however, no significant impacts were found for male firearm homicide
victimization. Findings suggest there may be value in preventing legal access to
firearms by persons who have a history of intimate partner violence, although
considerable further study is required.
PMID- 29332508
TI - Battered Wives or Dependent Mothers? Negotiating Familial Ideology in Law.
AB - More than a decade after its passing, Sri Lanka's Prevention of Domestic Violence
Act (PDVA) remains a remedy of last resort for female survivors of intimate
partner violence, as there is little support to take on a rights-defined identity
as a battered woman both inside and outside the courtroom. However, large numbers
of women are accessing the Maintenance Act of 1999 to exit violent relationships
without the censure and stigma that attaches to the PDVA. The key to
understanding this phenomenon is to consider how familial ideology works in
unpredictable ways within the Sri Lankan judicial system. This article examines
the reach and different impacts of familial ideology within the judiciary and
argues that female survivors of violence navigate this ideology to their own
advantage. However, the preference to address violence through the Maintenance
Act renders such violence invisible. The price for judicial redress is silence.
PMID- 29332509
TI - Sexual Scripts and Criminal Statutes: Gender Restrictions, Spousal Allowances,
and Victim Accountability After Rape Law Reform.
AB - The author provides a mixed-methods assessment of U.S. rape statutes to assess
progress in reform. Contemporary statutes offer restrictive frameworks for
distinguishing criminal from noncriminal sexual violence, many of which are
grounded in gendered and heterosexist assumptions. Fourteen states retain gender
restrictions in rape statutes. Twenty maintain marital distinctions that limit
accountability for spousal rape. Furthermore, whereas explicit resistance
requirements have been eliminated nationwide, implicit resistance expectations
manifest through emphasis on physical force and involuntary intoxication.
Analyses conclude with recommendations for further legal reform and a discussion
of the potential for legislation to affect broader social perceptions of rape.
PMID- 29332510
TI - Localized autoimmune pancreatitis mimicking pancreatic cancer: Case report and
literature review.
AB - Autoimmune pancreatitis (AP) is a rare autoimmune pancreatic manifestation of
systemic immunoglobulin G4 (IgG4)-related sclerosing disease. Distinguishing
between AP and pancreatic cancer is crucial because the clinical courses,
treatments, and prognoses of these two disease entities are quite different. We
herein report a case involving a 52-year-old man with subacute epigastralgia who
visited our hospital for evaluation of a suspicious pancreatic mass found during
esophagogastroduodenoscopy. Enhanced computed tomography (CT) revealed an
enlarged lesion in the pancreatic head with encasement of hepatic vessels. The
lesion also exhibited increased 18F-fluorodeoxyglucose accumulation on positron
emission tomography/CT imaging, which was highly suggestive of pancreatic cancer.
After open biopsy, morphologic examination showed an inflammatory infiltrate in
the pancreas, which was compatible with chronic sclerotic pancreatitis. Further
laboratory tests revealed an elevated serum IgG4 level, and the diagnosis of
sclerotic pancreatitis was then confirmed. After corticosteroid treatment, the
pancreatic lesion showed shrinkage on follow-up CT, and the serum IgG4 titer
decreased to the normal range. This case suggests that clinicians should be
familiar with the clinical presentations and diagnostic criteria of AP versus
pancreatic cancer. An awareness of the differences between these diseases may
avoid misdiagnosis and unnecessary surgical intervention.
PMID- 29332511
TI - The Process of Primary Desistance From Intimate Partner Violence.
AB - This study examined the interaction between structure and agency for individuals
in the first or early phase of primary desistance (1 year offending free) from
intimate partner violence (IPV). Narrative accounts of perpetrators, survivors,
and IPV program facilitators were analyzed using Thematic Analysis. Changes in
the self and the contexts, structures, and conditions were necessary to promote
desistance. Perpetrators made behavioral and cognitive changes taking on
different identities (agentic role) by removing external stressors and
instability within the confines of a supportive environment (structural role).
Findings provide a theoretical framework of desistance from IPV that integrates
social processes and subjective change.
PMID- 29332512
TI - Rape Aggression Defense: Unique Self-Efficacy Benefits for Survivors of Sexual
Trauma.
AB - Self-defense training is consistently linked to psychological benefits for
survivors of sexual trauma, yet little is known about how training may uniquely
benefit survivors compared with their nonsurvivor peers enrolled in the same
course. Path analysis was used to examine how history of sexual trauma impacts
pre- and post-training scores on three domains of self-efficacy using a national
sample of Rape Aggression Defense (RAD) participants. All participants reported
significant increases in self-efficacy domains, and sexual trauma history
significantly predicted pre-training interpersonal self-efficacy and post
training self-defense self-efficacy, suggesting that self-defense training
confers benefits for survivors above and beyond benefits for other participants.
PMID- 29332513
TI - The Meaning of Choosing a Spouse Among Ultra-Orthodox Jewish Women Who Found
Themselves in a Violent Relationship.
AB - This research note addresses how ultra-Orthodox Jewish women in Israel coping
with intimate partner violence experienced the spouse selection process. In-depth
semistructured qualitative-phenomenological interviews were conducted with 17
women. Four major themes emerged: (a) "The matchmaker seemingly fell asleep on
her watch"; (b) The parents' mistakes; (c) "The rabbi told me to jump into the
water. Now he should hand me the paddles to get out!" The rabbi's role; and (d)
"That's it . . . I follow it blindly": The system. The findings add to the
professional knowledge about violent partnerships in the ultra-Orthodox Jewish
community in Israel.
PMID- 29332514
TI - Gender, Migration, and Exclusionary Citizenship Regimes: Conceptualizing
Transnational Abandonment of Wives as a Form of Violence Against Women.
AB - Based on life history narratives of 57 women in India and interviews with 21
practitioners, we document the neglect, abuse, and instrumental deprivation of
women's rights through the process of transnational abandonment. While gendered
local sociocultural milieus and economic norms contribute to these harms, they
are crucially enabled and sustained by transnational formal-legal frameworks.
Widening the explanatory lens for understanding domestic violence beyond the
family and community, we argue that in a globalized world, (inter)state policies
serve to construct these women as a subordinate category of citizens-"disposable
women"-who can be abused and abandoned with impunity.
PMID- 29332516
TI - Drivers of Intimate Partner Violence Against Women in Three Refugee Camps.
AB - This qualitative study examined the "drivers" of intimate partner violence (IPV)
against women in displacement to identify protective factors and patterns of
risk. Qualitative data were collected in three refugee camps in South Sudan,
Kenya, and Iraq ( N = 284). Findings revealed interrelated factors that triggered
and perpetuated IPV: gendered social norms and roles, destabilization of gender
norms and roles, men's substance use, women's separation from family, and rapid
remarriages and forced marriages. These factors paint a picture of individual,
family, community and societal processes that exacerbate women's risk of IPV in
extreme conditions created by displacement. Implications for policy and practice
are indicated.
PMID- 29332515
TI - Vasoplegia in patients with sepsis and septic shock: pathways and mechanisms.
AB - Sepsis is one of the most frequent causes of death among patients in intensive
care units. Many therapeutic strategies have been assessed without the desired
success rates. A key risk factor for death is hypotension due to vasodilatation
with vascular hyposensitivity. However, the pathways underlying this process
remain unclear. Endotoxemia induces inflammatory mediators, and this is followed
by vasoplegia and decreased cardiac contractility. Although inhibition of these
mediators diminishes mortality rates in animal models, this phenomenon has not
been confirmed in humans. Downregulation of vasoconstrictive receptors such as
angiotensin receptors, adrenergic and vasopressin receptors is seen in sepsis,
which is associated with a hyporesponsiveness to vasoconstrictive mediators.
Animal studies have verified that receptor downregulation is linked to the above
mentioned inflammatory mediators. Anti-inflammatory therapy with glucocorticoids
reportedly improves responsiveness to catecholamines with higher survival in
rats, although this has not been shown to be clinically significant in humans.
Hence, there is an urgent need for in-depth studies investigating the underlying
mechanisms of vasoplegia to allow for development of effective therapeutic
strategies for the treatment of sepsis.
PMID- 29332517
TI - Women's Decisions to Stay in or Leave an Abusive Relationship: Results From a
Longitudinal Study in Bolivia.
AB - This study examined Bolivian women's decisions to stay with or leave their
violent partners. The theory of planned behavior (TPB) was used as the
theoretical framework. One hundred thirty-four women were assessed 3 times over 6
months. The TPB constructs were measured at T1 and T2; relationship status was
assessed at T3. At T2, attitudes about staying and leaving predicted the
intention to leave. Intention to leave at T2 but not at T1 predicted relationship
status at T3. These results suggest that the decision to leave was consolidated
between T1 and T2, and attitudes toward staying were most relevant to this
decision.
PMID- 29332518
TI - Sexual Assault and Dyadic Relationship Satisfaction: Indirect Associations
Through Intimacy and Mental Health.
AB - Rates of child and adult sexual assault (SA) among women are staggering and place
women at risk for intra- and interpersonal difficulties. However, the independent
contributions of child and adult SA or the mechanisms of this risk are unknown.
This study's goal was to examine the indirect effects of child and adult SA on
women's own and partner's relationship functioning through their impact on
women's mental health, emotional intimacy, and sexual intimacy. Results revealed
that the association of women's child SA with both her own and her partner's
relationship satisfaction operated through emotional intimacy. Considerations for
the study of women with a history of SA in the context of couple functioning are
discussed.
PMID- 29332519
TI - Integrating Reproductive Health Services Into Intimate Partner and Sexual
Violence Victim Service Programs.
AB - This study assessed the feasibility of integrating reproductive health services
into intimate partner violence/sexual violence (IPV/SV) programs. After a
training for victim service agencies on integration of health services, we
conducted semistructured interviews with IPV/SV program leadership. Leadership
reported advocates were more likely to recognize the need to refer clients to
health services, and revealed challenges operationalizing partnerships with
health care centers. Training to integrate basic health assessment into victim
services may be one way to address women's urgent health needs. Formal
partnership agreements, protocols to facilitate referrals, and opportunities to
cross-train are needed to nurture these cross-sector collaborations.
PMID- 29332520
TI - Gender-Based Violence Among HIV-Positive Women in Kazakhstan: Prevalence, Types,
and Associated Risk and Protective Factors.
AB - This article examines the prevalence and associated multilevel risk and
protective factors of intimate and nonintimate partner violence among a sample of
249 HIV-positive women in Kazakhstan. We found high prevalence of both lifetime
intimate partner violence (52%) and nonintimate partner violence (30%). Together,
nearly 60% experienced at least one incident of violence by either an intimate or
nonintimate partner (gender-based violence [GBV]). In the multivariate analyses,
we found associations between several individual, interpersonal, and socio
structural risk factors and GBV. Findings provide direction for practice, policy,
and future research to address the intersection of GBV and HIV in Kazakhstan.
PMID- 29332522
TI - I Said No: The Impact of Voicing Non-Consent on Women's Perceptions of and
Responses to Rape.
AB - The current study explored the impact of voicing non-consent in relation to rape.
Aims of the study included determining (a) the prevalence of voicing non-consent,
(b) the relationship of voicing non-consent to verbal and physical resistance,
and (c) whether voicing non-consent predicts distress and rape acknowledgment.
Out of 262 college women who experienced rape, 81% voiced non-consent. Voicing
non-consent was related to verbal and physical resistance, but was distinct in
prevalence and prediction of distress. Voicing non-consent was associated with
trauma-related symptoms in multivariate models. Women who voiced non-consent were
more likely to acknowledge their experience as rape or sexual assault.
Implications are discussed.
PMID- 29332521
TI - A Template Analysis of Intimate Partner Violence Survivors' Experiences of Animal
Maltreatment: Implications for Safety Planning and Intervention.
AB - This study explores the intersection of intimate partner violence (IPV) and
animal cruelty in an ethnically diverse sample of 103 pet-owning IPV survivors
recruited from community-based domestic violence programs. Template analysis
revealed five themes: (a) Animal Maltreatment by Partner as a Tactic of Coercive
Power and Control, (b) Animal Maltreatment by Partner as Discipline or Punishment
of Pet, (c) Animal Maltreatment by Children, (d) Emotional and Psychological
Impact of Animal Maltreatment Exposure, and (e) Pets as an Obstacle to Effective
Safety Planning. Results demonstrate the potential impact of animal maltreatment
exposure on women and child IPV survivors' health and safety.
PMID- 29332523
TI - Challenging Narratives of the Anti-Rape Movement's Decline.
AB - A recent trend in scholarship characterizes the anti-rape movement as founded
with radical goals and achieving success at reforming rape laws, but then
declining because of co-optation by the state. This article challenges narratives
of decline in light of the history of the anti-rape movement and current anti
rape activism. By focusing their critique on criminal justice and therapeutic
approaches to sexual violence, and failing to account for the diversity of the
anti-rape movement, advocates for narratives of decline ignore parts of the
movement that challenge the state and other parts that use broader cultural and
community-based strategies to end rape.
PMID- 29332524
TI - Exploring the Moderating Role of Problematic Substance Use in the Relations
Between Borderline and Antisocial Personality Features and Intimate Partner
Violence.
AB - Borderline and antisocial personality features relate to multiple externalizing
behaviors, including intimate partner violence (IPV). However, not all
individuals with borderline and antisocial traits perpetrate IPV. The strength of
the personality-IPV link may be related to problematic substance use. We examined
borderline and antisocial personality features, problematic substance use, and
IPV in a community sample of couples. Positive relations between both borderline
and antisocial features and IPV were stronger in conditions of high problematic
alcohol use relative to low problematic alcohol use. Alcohol misuse may be an
important factor to consider for IPV reduction in men with these personality
features.
PMID- 29332525
TI - Bar Training for Active Bystanders: Evaluation of a Community-Based Bystander
Intervention Program.
AB - Bystander intervention programs are proliferating on college campuses and are
slowly gaining momentum as sexual violence prevention programs suitable for the
larger community. In particular, bystander intervention programs aimed at bar
staff have been developed in a number of locations. This study entails the
exploratory evaluation of a community-based bystander program for bar staff.
Using a pre-posttest design, this study suggests that evidence surrounding the
effectiveness of this program is promising as it decreases rape myths, decreases
barriers to intervention, and increases bartenders willingness to intervene.
Future research and policy implications are discussed.
PMID- 29332526
TI - The Effects of Victim Age, Perceiver Gender, and Parental Status on Perceptions
of Victim Culpability When Girls or Women Are Sexually Abused.
AB - This study investigated perceptions of victim culpability in sexual assaults
against girls and women according to victim age, perceiver gender, and perceiver
parental status. Overall, 420 jury-eligible participants completed an online
survey recording their attributions of guilt, responsibility, and blame toward 10
, 15-, and 20-year-old girls and women in relation to sexual assault.
Attributions of culpability were affected by whether the victim physically or
verbally resisted the abuse, wore sexually revealing clothes, or was described as
having acted promiscuously. Fifteen-year-old victims were perceived as more
culpable for the abuse than 10-year-old victims. Implications of these findings
are discussed.
PMID- 29332527
TI - Domestic Violence Counseling in Rural Northern China: Gender, Social Harmony, and
Human Rights.
AB - Domestic violence (DV) affects over a third of Chinese women in a relationship.
Focusing on ethnographic data from six staff members and six DV survivors at a
rural, state-affiliated women's center in China in 2010, this article relies on
Henrietta Moore's notion of the poststructuralist gendered subject to examine how
the staff draw on discourses about gender and social harmony in persuading women
to stay in their marriages, rather than on human rights discourses that emphasize
survivor safety. It shows that DV survivors are frequently sent back to dangerous
homes where their health is placed at risk.
PMID- 29332528
TI - "Killed Out of Love": A Frame Analysis of Domestic Violence Coverage in Hong
Kong.
AB - A frame analysis was conducted on a Hong Kong newspaper to determine whether news
coverage of female fatalities at the hands of their intimate partners was
reported in conventional domestic violence ways or if there were culture-specific
explanations. Overall, most coverage supported known views of domestic violence,
justifying the perpetrator and categorizing the issue as isolated crime. However,
a few stories highlighted the historical subordination of women under patriarchy
in Confucianism as an important cultural factor. Findings have implications for
the lack of generalization of the social problem, and the understanding of
cultural and political power in Hong Kong society.
PMID- 29332529
TI - Alcohol-Related Victim Behavior and Rape Myth Acceptance as Predictors of Victim
Blame in Sexual Assault Cases.
AB - Two studies analyzed the influence of victim behavior, drink type, and observer
rape myth acceptance (RMA) on attributions of blame to victims of sexual assault.
In Study 1, people higher in RMA blamed the victim more when she accepted rather
than rejected the aggressor's invitation to buy her a drink. In Study 2, we
analyzed if the effects depended on who offered the invitation for a drink (a
friend or aggressor). RMA was more closely related to victim blame when she
accepted (vs. rejected) the offer of a drink from the aggressor. In both studies,
drink type (alcoholic vs. nonalcoholic) did not interact with the other
variables.
PMID- 29332530
TI - Reconciliation of patient/doctor vocabulary in a structured resource.
AB - Today, social media is increasingly used by patients to openly discuss their
health. Mining automatically such data is a challenging task because of the non
structured nature of the text and the use of many abbreviations and the slang
terms. Our goal is to use Patient Authored Text to build a French Consumer Health
Vocabulary on breast cancer field, by collecting various kinds of non-experts'
expressions that are related to their diseases and then compare them to
biomedical terms used by health care professionals. We combine several methods of
the literature based on linguistic and statistical approaches to extract
candidate terms used by non-experts and to link them to expert terms. We use
messages extracted from the forum on ' cancerdusein.org ' and a vocabulary
dedicated to breast cancer elaborated by the Institut National Du Cancer. We have
built an efficient vocabulary composed of 192 validated relationships and
formalized in Simple Knowledge Organization System ontology.
PMID- 29332531
TI - Supporting Rape Survivors Through the Criminal Injuries Compensation Scheme: An
Exploration of English and Welsh Independent Sexual Violence Advisors'
Experiences.
AB - English and Welsh responses to rape have long been critically examined, leading
to attempted improvements in the criminal justice system. Despite this, little
attention has been paid to the Criminal Injuries Compensation Scheme (CICS) and
the difficulties applying it to rape. To begin addressing this gap, researchers
interviewed three, and qualitatively surveyed 22, Independent Sexual Violence
Advisors. The findings suggest that CICS may not only reinforce rape myths and
disadvantage vulnerable survivors, but is also a source of validation and
contributes to survivor justice. The study, while exploratory, therefore,
highlights the need for further discussion about rape survivor compensation.
PMID- 29332532
TI - Is the End Really the End? Prevalence and Correlates of College Women's
Intentions to Return to an Abusive Relationship.
AB - Fifty-six college women completed surveys before and after terminating an
abusive, heterosexual dating relationship. Whereas 64% of women had contact with
their abusive partner post break-up, only 14% reported a moderate to high
likelihood that they would return. Intentions to return were prospectively
predicted by fewer perceived quality of alternatives, and cross-sectional
correlates of intentions to return were being single, shorter time since
relationship termination, having contact with one's abusive ex-partner, and
social pressure to return. These data can be used to inform intervention and
advocacy efforts and to guide future research.
PMID- 29332533
TI - Assessing the Impact of a Focused Deterrence Strategy to Combat Intimate Partner
Domestic Violence.
AB - The Offender Focused Domestic Violence Initiative (OFDVI) represents for the
first time anywhere the application of the evidence-based focused deterrence
policing approach to combat intimate partner domestic violence (IPDV). Through
holding offenders accountable, the strategy has resulted in 20% reductions each
in IPDV-related calls for police service and arrests. Victim injuries have been
significantly reduced and the 1-year IPDV offender recidivism rate is about 16
17%. The backbone of the OFDVI strategy is the multidisciplinary collaboration of
law enforcement and community partners which has resulted in identification and
resolving system issues which have historically allowed offenders to repeat IPDV
without consequence.
PMID- 29332534
TI - Mediated Effects of Coping on Mental Health Outcomes of African American Women
Exposed to Physical and Psychological Abuse.
AB - Few studies have assessed the individual symptoms of posttraumatic stress
disorder (PTSD) as separate mental health consequences of intimate partner abuse
(IPA). This study examined the role of coping strategies associated with symptoms
of PTSD in a community sample of African American women who have experienced
abuse ( N = 128). The results revealed that nonphysical abuse was more prevalent
than physical abuse. Specific symptoms of PTSD expressed depended on the type of
abuse experienced and the type of coping strategies utilized. The findings have
multiple implications on how IPA is studied as well as its clinical screening and
treatment processes.
PMID- 29332535
TI - Viewing Gendered Violence in Guatemala Through Photovoice.
AB - This research examined rural and urban women's experiences of gender-based
violence in Chimaltenango, Guatemala. Photovoice methodology was used to describe
and analyze local realities and vulnerabilities, and ethnographic techniques
added cultural and contextual factors. While the initial focus was on intimate
partner violence, results showed that violence for women exists from childhood to
senior years. Participants noted gaps in services and participated in a public
strategy workshop to address these. Challenges and opportunities are presented
around the enduring and complex global crisis of gendered violence. Photovoice is
a powerful method for organizations to better understand and respond to local
issues.
PMID- 29332536
TI - The Rise of the Crime Victim and Punitive Policies? Changes to the Legal
Regulation of Intimate Partner Violence in Finland.
AB - This article examines intimate partnership violence as a question of criminal
justice policy in Finland, and contributes to criminological discussions
regarding oft-stated connections between the politicization of the victim, the
treatment of offenders, and repressive criminal justice policies. In this
discussion, legislation aiming to regulate and prevent violence against women has
often been utilized as an example of such punitive policies. Although criminal
policies in Nordic countries differ significantly from more punitive Anglophone
policies, punitive tendencies, it has been argued, have increased in the former,
too. This article analyzes the change in legal regulations and the criminal
political status of intimate partner violence in Finland between 1990 and 2004,
while examining the juxtaposition of victims and offenders alongside repressive
demands.
PMID- 29332537
TI - AZD9291 Increases Sensitivity to Radiation in PC-9-IR Cells by Delaying DNA
Damage Repair after Irradiation and Inducing Apoptosis.
AB - AZD9291 is a novel, irreversible epidermal growth factor receptor (EGFR) tyrosine
kinase inhibitor (TKI), which is administered orally. It has been proven
effective in non-small cell lung cancer (NSCLC) patients, with both EGFR
sensitizing and EGFR T790M mutations in preclinical models. However, the
potential therapeutic effects of AZD9291 combined with other modalities,
including ionizing radiation, are not well understood. The presence of AZD9291
significantly increases the cell-killing effects of radiation in PC-9-IR cells
with a secondary EGFR mutation (T790M), which was developed from NSCLC PC-9 cells
(human lung adenocarcinoma cell with EGFR 19 exon 15 bp deletion) after chronic
exposure to increasing doses of gefitinib, and in H1975 cells (human lung
adenocarcinoma cell with EGFR exon 20 T790M mutation de novo), but not in PC-9
cells or in H460 cells (human lung adenocarcinoma cell with wild-type EGFR). In
PC-9-IR cells, AZD9291 remarkably decreases phosphorylation levels of EGFR,
extracellular regulated protein kinase (ERK), and protein kinase B (AKT). AZD9291
increases sensitivity to radiation in PC-9-IR cells by delaying deoxyribonucleic
acid (DNA) damage repair after irradiation and inducing apoptosis, and enhances
tumor growth inhibition when combined with radiation in PC-9-IR xenografts. Our
findings suggest a potential therapeutic effect of AZD9291 as a radiation
sensitizer in lung cancer cells with an acquired EGFR T790M mutation, providing a
rationale for a clinical trial using the combination of AZD9291 and radiation in
NSCLCs harboring acquired T790M mutation.
PMID- 29332539
TI - Whole-Body Oxygen (16O) Ion-Exposure-Induced Impairments in Social Odor
Recognition Memory in Rats are Dose and Time Dependent.
AB - Future long-duration space missions will involve travel outside of the Earth's
magnetosphere, which will result in increased radiation exposure for astronauts.
Exposure could permanently damage multiple tissues, including the central nervous
system (CNS), and result in deleterious effects on cognition and behavior during
and beyond the mission. Here, we assessed the effects of whole-body oxygen ion
(16O; 1,000 MeV/n) exposure (5 or 25 cGy) on social odor recognition memory in
male Long-Evans rats at one and six months after exposure. At one month
postirradiation, all rats displayed a preference for a novel 1 (N1) social odor
experienced during the habituation phase. When assessed for recognition memory 24
h later, only sham-irradiated rats spent more time exploring a second novel
social odor (novel 2, N2), whereas rats irradiated with 5 or 25 cGy 16O ions did
not show a preference for the N2 odor compared to the N1 odor experienced 24 h
earlier, thus displaying a memory deficit for recall of the social odor
encountered 24 h prior. At six months postirradiation, rats exposed to 25 cGy
showed persistent deficits in 24 h recognition memory, while the 5 cGy-exposed
rats did not. Thus, 24 h recognition memory was apparently recovered at six
months postirradiation for the low, but not the higher, dose of 16O ions. Both
irradiated groups displayed similar numbers of Ki67+ cells, a marker of cell
proliferation, in the subventricular zone. These results further demonstrate that
space-relevant 16O ion exposure has deleterious effects on the CNS, which are
related to both radiation dose and time after exposure.
PMID- 29332540
TI - Using the Woman Abuse Screening Tool to Screen for and Assess Dating Violence in
College Students.
AB - The study aimed to evaluate the measurement properties of the Woman Abuse
Screening Tool (WAST) in Chinese college students. A cross-sectional survey was
conducted in Hong Kong. A cutoff score of 10 was found to be able to discriminate
between abused and nonabused Chinese young adults. The total score was
significantly correlated with total scores for anxiety and depression on the
Chinese version of the Hospital Anxiety and Depression Scale. Two-factor
structure of the WAST was supported by exploratory and confirmatory factor
analyses. The Chinese WAST was found to be valid in screening for and assessing
intimate partner violence.
PMID- 29332541
TI - After the Escape: Physical Abuse of Offspring, Posttraumatic Stress Disorder, and
the Legacy of Political Violence in the DPRK.
AB - What is the relationship between victimization by political violence against
women in North Korea and later physical abuse of offspring? This article examines
the relationships between victimization by political violence, posttraumatic
stress disorder (PTSD), alcohol abuse/dependence, and abuse of offspring after
arrival in South Korea. A random sample of 204 female North Korean defectors was
used to test hypotheses. An oral history conducted with a survivor of North
Korean political violence is provided in an appendix to contextualize the
results. Analyses established a significant link between previous victimization
by political violence and abuse of offspring but not mediation by either PTSD or
alcohol abuse/dependence.
PMID- 29332542
TI - Long Journeys Toward Freedom: The Relationship Between Coercive Control and Space
for Action-Measurement and Emerging Evidence.
AB - We report on the development of, and findings from, two scales measuring coercive
control and space for action over a period of 3 years in a sample of 100 women
who had accessed domestic violence services. We present statistical evidence to
show a significant correlation between coercive control and space for action.
However, dealing with violence is not a linear process, and support needs to
extend beyond being enabled to separate. The scales advance measurement of
women's experience of coercive control and, through the space for action scale,
document their ability to restore agency and freedom in contexts of relative
safety.
PMID- 29332538
TI - Role of Infiltrating Monocytes in the Development of Radiation-Induced Pulmonary
Fibrosis.
AB - Lung exposure to radiation induces an injury response that includes the release
of cytokines and chemotactic mediators; these signals recruit immune cells to
execute inflammatory and wound-healing processes. However, radiation alters the
pulmonary microenvironment, dysregulating the immune responses and preventing a
return to homeostasis. Importantly, dysregulation is observed as a chronic
inflammation, which can progress into pneumonitis and promote pulmonary fibrosis;
inflammatory monocytes, which are bone marrow derived and express CCR2, have been
shown to migrate into the lung after radiation exposure. Although the extent to
which recruited inflammatory monocytes contribute to radiation-induced pulmonary
fibrosis has not been fully investigated, we hypothesize that its pathogenesis is
reliant on this population. The CC chemokine ligand, CCL2, is a chemotactic
mediator responsible for trafficking of CCR2+ inflammatory cells into the lung.
Therefore, the contribution of this mediator to fibrosis development was
analyzed. Interleukin (IL)-1beta, a potent pro-inflammatory cytokine expressed
during the radiation response, and its receptor, IL-1R1, were also evaluated. To
this end, CCR2-/-, IL-1beta-/- and IL-1R1-/- chimeric mice were generated and
exposed to 12.5 Gy thoracic radiation, and their response was compared to wild
type (C57BL/6) syngeneic controls. Fibrotic foci were observed in the periphery
of the lungs of C57 syngeneic mice and CCR2-/- recipient mice that received C57
bone marrow (C57 > CCR2-/-) by 16 and 12 weeks after irradiation, respectively.
In contrast, in the mice that had received bone marrow lacking CCR2 (CCR2-/- >
C57 and CCR2-/- syngeneic mice), no pulmonary fibrosis was observed at 22 weeks
postirradiation. This observation correlated with decreased numbers of
infiltrating and interstitial macrophages compared to controls, as well as
reduced proportions of pro-inflammatory Ly6C+ macrophages observed at 12-18 weeks
postirradiation, suggesting that CCR2+ macrophages contribute to radiation
induced pulmonary fibrosis. Interestingly, reduced proportions of CD206+ lung
macrophages were also present at these time points in CCR2-/- chimeric mice,
regardless of donor bone marrow type, suggesting that the phenotype of resident
subsets may be influenced by CCR2. Furthermore, chimeras, in which either IL
1beta was ablated from infiltrating cells or IL-1R1 from lung tissues, were also
protected from fibrosis development, correlating with attenuated CCL2 production;
these data suggest that IL-1beta may influence chemotactic signaling after
irradiation. Overall, our data suggest that CCR2+ infiltrating monocyte-derived
macrophages may play a critical role in the development of radiation-induced
pulmonary fibrosis.
PMID- 29332543
TI - Difficult but Close Relationships: Children's Perspectives on Relationships With
Their Mothers in the Context of Domestic Violence.
AB - This article reports findings from a participative and qualitative study
conducted with children who had experienced domestic violence, focusing on their
perspectives on their relationships with their mothers. Three focus groups and 46
individual interviews were conducted with children to gather their experiences.
The research findings demonstrate that women's and children's victimizations are
inextricably linked, and that domestic violence affects mother-child
relationships. They also show that, despite the challenges and difficulties,
children generally consider their mothers as very significant individuals in
their lives, and have close relationships with them. The findings also reveal a
dynamic of mutual protectiveness.
PMID- 29332544
TI - The Possible Use of Preoperative Natriuretic Peptides for Discriminating Low
Versus Moderate-High Surgical Risk Patient.
AB - Perioperative risk scores for patients undergoing noncardiac surgery are
generally considered inaccurate, poor, or, at best, modest. We propose estimating
a patient's pretest and posttest probability of cardiac morbidity and death using
the preoperative scoring system plus the negative likelihood ratio from brain
natriuretic peptide (BNP) or N-terminal proB-type natriuretic peptide (NT-proBNP)
plasma levels. Our clinical challenge scenario showed a pretest probability of
postoperative major cardiac complications with the patient risk factor as 6.6%
for the Revised Cardiac Risk Index and between 1% and 5% (intermediate risk) per
the recent European Society of Cardiology and the European Society of
Anesthesiologist guidelines for surgical risk estimation. In fact, the American
College of Cardiology and the American Heart Association guidelines consider the
same surgical procedure for elevated risk. The posttest probability takes
advantage of a negative likelihood ratio from BNP plasma levels, with patient
risk factor reduced to 0.8% and surgical risk to 1.1%. In the same way, the
pretest American College of Surgeons National Surgical Quality Improvement
Program score decreased from 18.8% to 3.5% for severe complications and from 0.9%
to 0.1% for death at <=90 days. Following noncardiac surgery, postoperative
complications and mortality are often cardiac in nature. The negative likelihood
ratio of BNP and NT-proBNP plasma levels provides a quick, low-cost tool for
recognizing and reclassifying the cardiovascular risk of those undergoing
noncardiac surgery, thereby singling out low- versus moderate-high-risk surgical
patients.
PMID- 29332546
TI - Drinking Motives as a Moderator of the Relationship Between Dating Violence
Victimization and Alcohol Problems.
AB - The present study sought to examine whether drinking motives (i.e., coping,
social, conformity, and enhancement) moderated the relationship between physical,
sexual, and psychological dating violence victimization and alcohol-related
problems in a sample of drinking college women ( N = 177). Results demonstrated
that coping and social drinking motives moderated the relationship between sexual
victimization and alcohol problems; conformity, social, and enhancement drinking
motives moderated the relationship between alcohol-related problems and physical
victimization; no significant findings were evident for psychological aggression
victimization. Our results partially support the self-medication model of alcohol
use, and this may be particularly relevant to sexual victimization.
PMID- 29332545
TI - Long Noncoding RNA H19 Inhibits Cell Viability, Migration, and Invasion Via
Downregulation of IRS-1 in Thyroid Cancer Cells.
AB - Thyroid cancer is a common endocrine gland malignancy which exhibited rapid
increased incidence worldwide in recent decades. This study was aimed to
investigate the role of long noncoding RNA H19 in thyroid cancer. Long noncoding
RNA H19 was overexpressed or knockdown in thyroid cancer cells SW579 and TPC-1,
and the expression of long noncoding RNA H19 was detected by real-time polymerase
chain reaction. The cell viability, migration, and invasion were determined by 3
(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide assay,
Transwell assay, and wound healing assay, respectively. Furthermore, cell
apoptosis was analyzed by flow cytometry, and expressions of some factors that
were related to phosphatidyl inositide 3-kinases/protein kinase B and nuclear
factor kappaB signal pathway were measured by Western blotting. This study
revealed that cell viability and migration/invasion of SW579 and TPC-1 were
significantly decreased by long noncoding RNA H19 overexpression compared with
the control group ( P < .05), whereas cell apoptosis was statistically increased
( P < .001). Meanwhile, cell viability and migration/invasion were significantly
increased after long noncoding RNA H19 knockdown ( P < .05). Furthermore, long
noncoding RNA H19 negatively regulated the expression of insulin receptor
substrate 1 and thus effect on cell proliferation and apoptosis. Insulin receptor
substrate 1 regulated the activation of phosphatidyl inositide 3-kinases/AKT and
nuclear factor kappaB signal pathways. In conclusion, long noncoding RNA H19
could suppress cell viability, migration, and invasion via downregulation of
insulin receptor substrate 1 in SW579 and TPC-1 cells. These results suggested
the important role of long noncoding RNA H19 in thyroid cancer, and long
noncoding RNA H19 might be a potential target of thyroid cancer treatment.
PMID- 29332547
TI - The Psychology of the Politics of Rape: Political Ideology, Moral Foundations,
and Attitudes Toward Rape.
AB - Previous research has found that conservatives and liberals emphasize different
moral foundations. The purpose of these two studies was to investigate whether
moral foundations mediate the relationship between political ideology and
attitudes toward rape among U.S. college students. In Study 1, moral foundations
fully mediated the relationship between political ideology and rape myth
acceptance. Study 2 generally replicated the results of Study 1, with binding
foundations demonstrating the most consistent mediating effects. These results
suggest that individual differences in moral decision-making may explain the
relationship between political ideology and attitudes toward rape.
PMID- 29332548
TI - Sociodemographic and Incident Variables as Predictors of Victim Injury From
Intimate Partner Violence: Findings From Police Reports.
AB - Predictors of victim injury from intimate partner violence (IPV) were
investigated using 1,292 police reports collected in South Carolina in 2009/2010.
All cases were opposite sex adults. Results from bivariate statistics showed that
IPV cases with ( n = 649) and without visible injuries ( n = 643) differed on
victim gender, victim race, type of relationship, and perpetrator's alcohol use.
Results from a logistic regression analysis predicting victim injury showed
higher odds ratios for males, Whites, and couples identified as cohabitants.
Although most victims, including most injured victims, were Black women, males
and Whites were overrepresented in the injured group.
PMID- 29332549
TI - The Role of Sexual Abuse in Trauma Symptoms, Delinquent and Suicidal Behaviors,
and Criminal Justice Outcomes Among Females in a Juvenile Justice Diversion
Program.
AB - Female juvenile justice-involved (JJI) youth experience more sexual abuse (SA)
than their non-JJI counterparts or their male JJI counterparts. This study
examines SA's role among JJI females ( N = 1,307) in a behavioral health
diversion program. Results indicate that SA increases the risk of psychological
trauma, particularly posttraumatic stress and depression. SA also increases the
odds of suicidal behavior, running away, and substance use. SA females have the
same odds of successfully completing behavioral health diversion and being
charged with any offense or misdemeanor after termination as non-SA females.
Implications of research and future directions are discussed.
PMID- 29332550
TI - How Ending Impunity for Conflict-Related Sexual Violence Overwhelmed the UN
Women, Peace, and Security Agenda: A Discursive Genealogy.
AB - The recent unprecedented focus on ending impunity for conflict-related sexual
violence (CRSV) is positive in many respects. However, it has narrowed the scope
of Security Council Resolution 1325 and the women, peace, and security (WPS)
agenda it established in 2000. Through a critical discursive genealogy of the
interrelation of two UN agendas-protection of civilians in armed conflict and
women, peace, and security-the author traces how CRSV emerged as the defining
issue of the latter while the transformative imperative of making women's
participation central to every UN endeavor for peace and security has failed to
gain traction.
PMID- 29332551
TI - How Narratives of Fear Shape Girls' Participation in Community Life in Two
Conflict-Affected Populations.
AB - Numerous social factors shape girls' lives in conflict-affected settings,
affecting their vulnerability to gender-based violence (GBV). Qualitative
research methods were used to examine spaces of perceived safety and risk for
girls living in two conflict-affected populations: camps in Ethiopia hosting
primarily South Sudanese and Sudanese refugees and communities in eastern
Democratic Republic of Congo. Three major themes emerged: (a) challenges around
caregiver-child communication regarding development, sex, and sexual violence;
(b) a typology of safe/risky spaces; and (c) the influence of male-dominated
spaces on experiences and fear of GBV. The findings have implications for
programs focused on reducing adolescent girls' vulnerability to violence within
conflict-affected contexts.
PMID- 29332553
TI - Understanding Trauma Normativeness, Normalization, and Help Seeking in Homeless
Mothers.
AB - Although trauma-informed approaches guide services to families experiencing
homelessness, more emphasis is placed on securing housing than addressing
underlying trauma contributing to housing instability. Examining the stories of
29 homeless and/or unstably housed mothers within the broader literature on
family trauma and violence, chronic illness, and cultural aspects of family
functioning, we define the process of trauma normativeness and normalization that
may occur with repeated trauma experiences and argue that rehousing efforts must
include concomitant attention to trauma and to understanding how individual,
family, community, and cultural factors influence help-seeking behaviors in this
vulnerable and growing population.
PMID- 29332554
TI - Evaluating the dose-dependent mechanism of action of trazodone by estimation of
occupancies for different brain neurotransmitter targets.
AB - Trazodone is a drug that was introduced in the clinic almost 40 years ago. It is
licensed to treat depression, but it is also commonly used off-label to treat
insomnia. A recent study shows that it could be promising in preventing
neurodegeneration in mice, and clinical trials to assess its possible beneficial
effects on dementia and Alzheimer's disease are expected to start soon in humans.
In this study, we describe the dose-dependent pharmacology of trazodone by
carrying out pharmacokinetic simulations aiming to predict the brain
concentrations of trazodone for different drug-dosing regimens and calculating
occupancy for 28 different targets for which published trazodone-binding data are
available. Our study indicates that low doses of trazodone (typically 50 mg
daily) should suffice to block specific receptors responsible for the hypnotic
effect, and to provide the protective effect against neuroinflammation and
neurodegeneration that could be beneficial in dementia. Higher doses are required
for an antidepressant effect. The occupancy of specific receptors at therapeutic
doses also explains peculiar side effects reported by patients treated with
trazodone (e.g. dry-mouth, hypotension and priapism).
PMID- 29332552
TI - Practitioner Views on the Impacts, Challenges, and Barriers in Supporting Older
Survivors of Sexual Violence.
AB - Despite half a century of research on both sexual violence and elder abuse, the
intersection between the two remains largely unexplored. Using theoretical lenses
of feminist criminology and critical feminist gerontology, this article explores
the intersection between age and sexual violence drawing on interviews with 23
practitioners supporting older survivors (aged 60 and over). They reported
physical and emotional effects of sexual violence leading to limited lifestyles,
disengagement from social networks, and reliance on pathogenic coping strategies.
Provision of effective support was complicated by challenges associated with
aging bodies and the social stigma associated with both sexual victimhood and
older age. Additional challenges lay in supporting older male survivors and those
living with dementia. The article ends by discussing implications for practice
and an agenda for future research.
PMID- 29332555
TI - Victim Empowerment, Safety, and Perpetrator Accountability Through Collaboration:
A Crisis to Transformation Conceptual Model.
AB - This article describes the development of the Victim Empowerment, Safety, and
Perpetrator Accountability through Collaboration (VESPAC) model based on a
grounded theory analysis of congressionally mandated and permissible purpose
areas for grants authorized by the Violence Against Women Act. These areas are
reflective of ongoing and emerging needs of victims and agencies serving victims
and are rooted in the expertise, insight, and concerns of those who work most
closely with victims and perpetrators on a regular basis. Analysis resulted in
five overarching and interconnected themes: Community Readiness, Victim Services,
Justice Responses, Coordinated Community Responses, and Cultural Relevance. The
final model emphasizes the centrality of coordinated community responses to
ensure that the remaining components of the model work in tandem across time to
achieve victim safety and perpetrator accountability in a culturally appropriate
way. The model also may help agencies, coalitions, and communities think "big"
and consider more strategically about where their strengths best fit in the vast
scope of victim needs necessary to meet safety goals and where they might benefit
most from the expertise of partners.
PMID- 29332556
TI - "Back Off Buddy, This Is My Body, Not Yours": Empowering Girls Through Self
Defense.
AB - Although growing recognition is being given to the benefits of teaching self
defense skills to college women, very little research attention has considered
the impacts of providing such courses to school-aged girls. This article presents
the findings from a large-scale evaluation of self-defense programs provided to
three different age groups of schoolgirls from diverse backgrounds in New
Zealand, drawing on survey responses from the girls themselves, supplemented by
qualitative data provided by key informant interviews with their school and self
defense teachers. The findings provide clear evidence of the many positive
benefits that can result for girls of all ages who participate in feminist self
defense courses taught by carefully trained instructors with a strong empowerment
focus.
PMID- 29332558
TI - Situational Variations in, and Women's Accounts of, Avoided Acts of Serious
Intimate Partner Violence.
AB - This study explores how both situations and persons contribute to the probability
that a serious incident of intimate partner violence (IPV) can be avoided. Data,
on both completed and avoided acts of serious partner violence, were collected
from jailed women in Baltimore. Factors that increase the odds of avoiding a
serious incident of IPV are a woman's age, her partner's initiation of a
threat/attack, and being accompanied by a family member. Factors that decrease
the odds of avoided serious violence include an indicator of what the dispute was
about, her partner's substance abuse, prior experiences with avoided acts of
violence, and lifetime arrests.
PMID- 29332557
TI - Evaluation of a Victim-Centered, Trauma-Informed Victim Notification Protocol for
Untested Sexual Assault Kits (SAKs).
AB - Throughout the United States, hundreds of thousands of sexual assault kits (SAKs)
have not been submitted by the police for forensic DNA testing, which raises
complex issues regarding how victims ought to be notified about what happened to
their kits. In this project, we evaluated a victim-centered, trauma-informed
victim notification protocol that was implemented in Detroit, Michigan. Most
victims (84%) did not have a strong negative emotional reaction to notification,
and most (57%) decided to reengage with the criminal justice system. Victims of
nonstranger sexual assaults were less likely to reengage postnotification
compared with victims of stranger rape.
PMID- 29332559
TI - The Relationship Between Domestic Partner Violence and Suicidal Behaviors in an
Adult Community Sample: Examining Hope Agency and Pathways as Protective Factors.
AB - We examined an additive and interactive model involving domestic partner violence
(DPV) and hope in accounting for suicidal behaviors in a sample of 98 community
adults. Results showed that DPV accounted for a significant amount of variance in
suicidal behaviors. Hope further augmented the prediction model and accounted for
suicidal behaviors beyond DPV. Finally, we found that DPV significantly
interacted with both dimensions of hope to further account for additional
variance in suicidal behaviors above and beyond the independent effects of DPV
and hope. Implications for the role of hope in the relationship between DPV and
suicidal behaviors are discussed.
PMID- 29332561
TI - Editorial.
PMID- 29332560
TI - Social Reactions to Sexual Assault Disclosure: A Qualitative Study of Informal
Support Dyads.
AB - This interview study examined 45 informal support dyads where sexual assault was
disclosed. Analysis showed social reactions and appraisals of reactions varied by
relationship type (family, friend, significant other). Themes identified were
role reversal or "parentification" of supporters, reactions of anger and
aggression toward perpetrators, supporters using their own trauma experiences to
respond to survivors, and reactions of betrayal. Results revealed the potential
for identifying relational patterns and dynamics occurring in social reactions
through dyadic analysis not otherwise captured by a survivor-only perspective.
This approach helps understand and address distinct relationship contexts to
improve supporters' reactions to sexual assault disclosure.
PMID- 29332562
TI - The Delicate Balance between the Good and the Bad IL-1 Proinflammatory Effects in
Endometriosis.
AB - BACKGROUND: Endometriosis is an inflammatory gynaecological disease with an
associated chronic inflammation. Interleukin(IL)-1 is one of the most important
immune and proinflammatory factors, produced mainly by monocytes and macrophages.
Studies indicate the role of the cytokine from IL-1 family in endometrium-related
disorders, particularly in endometriosis. METHODS: The information about the
impact of cytokine from IL-1 cytokine family on the pathogenesis and development
of endometriosis was obtained with an electronic literature search based on the
PubMed and Medline databases, spanning the period of January 1950 to July 2017
and includes associated references in the published studies. RESULTS: The
impairment of the IL-1 family cytokine-network may lead to changes in the
activation of immune system in the peritoneal cavity of women with endometriosis.
The aberrant ectopic endometrial cell properties of adhesion, implantation and
proliferation may be the result of a reduced suppressive capacity controlling the
IL-1. The imbalance between IL-1alpha, pro-IL-1beta, mature IL-1beta and sIL-1R2
and sIL-1RAcP in the peritoneal fluid and serum of women with endometriosis may
be linked to the ability of transforming an acute inflammation into a chronic
one. Despite the fact that peritoneal macrophages secrete more antiinflammatory
IL-1Ra and less proinflammatory IL-1 in the peritoneal cavity in affected women,
the inflammation still develops. CONCLUSIONS: This observation clearly suggested
a significant inadequacy in the specific regulatory mechanisms of IL-1 activity
at the peritoneal cavity level. The imbalance between all studied cytokines in
endometriosis may escalate peritoneal inflammation and, in consequence, develop
endometriosis.
PMID- 29332563
TI - Multi-Target Directed Drugs as a Modern Approach for Drug Design Towards
Alzheimer's Disease: An Update.
AB - Alzheimer's disease (AD) is a progressive multifactorial neurodegenerative
disorder. Currently, no effective treatment is available and this is due to
multiple factors involved in pathophysiology and severity of AD. A recent
approach for the rational design of new drug candidates, also called multitarget
directed ligands (MTDL) strategy, has been used to develop a variety of hybrid
compounds capable to act simultaneously in diverse biological targets. The
discovery of drug candidates capable of targeting multiple factors involved in AD
pathogenesis would greatly facilitate in improving therapeutic strategies. This
review is a complement to another review article, recently published by our
group, which covered the previous period of 2005-2012, and highlights recent
advances and examples of the exploitation of MTDLs approach in the rational
design of novel drug candidate prototypes for the treatment of AD.
PMID- 29332564
TI - Mesenchymal Stem Cell Therapy in Intracerebral Haemorrhagic Stroke.
AB - BACKGROUND: Spontaneous intracerebral haemorrhage (ICH) is a relatively common
fatal disease, with an overall global incidence estimated at 24.6 per 100,000
person- years. Given the high degree of morbidity and mortality associated with
ICH, therapies that may have neuroprotective effects are of increasing interest
to clinicians. In this last context, cell therapies offer the promise of
improving the disease course which cannot be addressed adequately by existing
treatments. OBJECTIVE: The aim of this review is to evaluate the protective
effects and molecular mechanisms of mesenchymal stem cells (MSCs) on haemorrhagic
brain following ICH. We also discuss possible emerging therapeutic approaches
worth of further research. METHODS AND RESULTS: The available literature on the
therapeutic potential of MSCs in ICH animal models clearly demonstrated that MSCs
enhance the functional recovery and reduce the volume of the infarct size
exerting anti-inflammatory and angiogenic properties. However, the quality of the
original articles investigating the efficacy of stem cell therapies in ICH animal
models is still poor and the lack of ICH clinical trial does not permit to reach
any relevant conclusions. CONCLUSION: Further studies have to be implemented in
order to achieve standardized methods of MSCs isolation, characterization and
administration to improve ICH treatments with MSCs or MSC-derived products.
PMID- 29332566
TI - Stimuli Responsive Nanoparticles for Controlled Anti-cancer Drug Release.
AB - Conventional drugs used for cancer chemotherapy have severe toxic side effects
and show individually varied therapeutic responses. The convergence of
nanotechnology, biology, material science and pharmacy offers a perspective
strategy for cancer chemotherapy. Nanoparticles loaded with anti-cancer drug have
been designed to overcome the limitations associated with conventional drugs,
several nanomedicines have been approved by FDA and shown good performances in
clinical practice. However, the therapeutic efficacies cannot be enhanced. Taking
this into account, stimuli responsive nanoparticles present the ability to
enhance therapeutic efficacy and reduce side effects. In this review, we
systematically summarized the recent progresses of controlled anti-cancer drug
release systems based on nanoparticles with different stimuli response including
pH, temperature, light, redox and others. If the achievements of the past can be
extrapolated into the future, it is highly likely that responsive nanoparticles
with a wide array of desirable properties can be eventually developed for safe
and efficient cancer therapy.
PMID- 29332565
TI - Beyond the "Lock and Key" Paradigm: Targeting Lipid Rafts to Induce the Selective
Apoptosis of Cancer Cells.
AB - For more than 40 years, the fluid mosaic model of cellular membranes has
supported our vision of an inert lipid bilayer containing membrane protein
receptors that are randomly hit by extracellular molecules to trigger
intracellular signaling events. However, the notion that compartmentalized
cholesterol- and sphingomyelin-rich membrane microdomains (known as lipid rafts)
spatially arrange receptors and effectors to promote kinetically favorable
interactions necessary for the signal transduction sounds much more realistic.
Despite their assumed importance for the dynamics of ligand-receptor
interactions, lipid rafts and biomembranes as a whole remain less explored than
the other classes of biomolecules because of the higher variability and
complexity of their membrane phases, which rarely provide the detailed atomic
level structural data in X-ray crystallography assays necessary for molecular
modeling studies. The fact that some alkylphospholipids (e.g. edelfosine: 1-O
octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) selectively induce the
apoptotic death of cancer cells by recruiting Fas death receptors and the
downstream signaling molecules into clusters of lipid rafts suggests these
potential drug targets deserve a more in-depth investigation. Herein, we review
the structure of lipid rafts, their role in apoptotic signaling pathways and
their potential role as drug targets for the treatment of cancer.
PMID- 29332567
TI - Nociceptin /Orphanin FQ Peptide (NOP) Receptor Modulators: An Update in Structure
Activity Relationships.
AB - Nociceptin /Orphanin FQ Peptide" receptor (NOPr) is a G-protein-coupled receptor
with the nociceptin/orphanin FQ peptide (N/OFQ) as endogenous agonist. It is
expressed in the nervous system as well as in some non-neural tissues. Its
activation has pronociceptive effect at the supraspinal level, whereas at the
spinal level it produces nociceptive effects at low doses and antinociceptive
effects at higher doses. NOPr is also involved in mood and blood pressure
regulation, immunoregulation, airway constriction, feeding, urination, bowel
motility, learning and memory. Selective NOPr agonists have been tested
clinically as anxiolytics and antitussives, and the antagonists as analgesics,
antidepressants and in the treatment of alcohol addiction. Two NOPr radioligands
have also been tested in humans as neuroimaging agents. Furthermore, the partial
agonist peptide SER100 and N/OFQ have been used in clinical trials, respectively
for congestive heart failure and overactive bladder. The evidence of interactions
between NOP and MU-opioid receptor (MOPr) receptors has been exploited in the use
of mixed NOPr/MOPr modulators as analgesics and in the treatment of drug
addiction. These drugs are devoid of typical opioid liabilities. In this review,
we outline the latest advances in the structure-activity relationships (SAR) of
NOPr agonists and antagonists, with emphasis on affinity, activity, selectivity
and pharmacokinetic features.
PMID- 29332568
TI - FGF-21 as a Potential Biomarker for Mitochondrial Diseases.
AB - The diagnosis of mitochondrial diseases is still challenging due to clinical and
genetical heterogeneity. The development of advanced technologies including Whole
Exome- Sequencing (WES) and Whole-Genome-Sequencing (WGS) has led to improvements
in genetic diagnosis. However, a reliable biomarker in serum could enhance and
ease the diagnosis and indeed reduce the need for muscle biopsy. Several studies
suggest Fibroblast growth factor 21 (FGF-21) as a biomarker for diagnosis in
mitochondrial disorders. It is known, that in patients with mitochondrial
disorders, the expression of FGF-21 gets elevated in an effort to counteract the
underlying metabolic deficiency. The growth and differentiation factor 15 (GDF
15) has been described as a potential biomarker for mitochondrial diseases, too.
In the present review, a literature research, using PubMed database about the
reliability of FGF-21 as a biomarker for mitochondrial disorders and its
comparison with GDF-15 has been performed.
PMID- 29332570
TI - Proprotein Convertase Subtilisin/kexin type 9 Inhibition in Cardiovascular
Prevention.
AB - Elevated levels of Low Density Lipoprotein cholesterol (LDL-C) are directly
associated with increased risk for atherosclerotic cardiovascular and
cerebrovascular events. Statins have been used to control serum LDLC and this has
translated into reduction in cardiovascular and cerebrovascular events. However,
despite high dose statin therapy, LDL-C control may remain inadequate in some
patients, particularly those with familial hypercholesterolemia. A new
therapeutic approach has emerged in recent years with proprotein convertase
subtilisin/kexin type 9 (PCSK9) inhibitors. In this review, we describe the
development and the use of this new class of drugs.
PMID- 29332569
TI - Cancer Treatment with Liposomes Based Drugs and Genes Co-delivery Systems.
AB - There are several mechanisms by which cancer cells develop resistance to
treatments, including increasing anti-apoptosis, increasing drug efflux, inducing
angiogenesis, enhancing DNA repair and altering cell cycle checkpoints. The drugs
are hard to reach curative effects due to these resistance mechanisms. It has
been suggested that liposomes based co-delivery systems, which can deliver drugs
and genes to the same tumor cells and exhibit synergistic anti-cancer effects,
could be used to overcome the resistance of cancer cells. As the co-delivery
systems could simultaneously block two or more pathways, this might promote the
death of cancer cells by sensitizing cells to death stimuli. This article
provides a brief review on the liposomes based co-delivery systems to overcome
cancer resistance by the synergistic effects of drugs and genes. Particularly,
the synergistic effects of combinatorial anticancer drugs and genes in various
cancer models employing multifunctional liposomes based co-delivery systems have
been discussed. This review also gives new insights into the challenges of
liposomes based co-delivery systems in the field of cancer therapy, by which we
hope to provide some suggestions on the development of liposomes based co
delivery systems.
PMID- 29332571
TI - Role of Heart Rate Reduction in the Management of Myocarditis.
AB - The morbidity of myocarditis demonstrates an upward tendency by years, is
commonly defined as the inflammation of myocytes and is caused by multiple
factors. With the development of the molecular biological technique, great
breakthroughs in the diagnosis and understanding of pathophysiological mechanisms
of myocarditis have recently been achieved. Several questions remain unresolved,
however, including standard treatment approaches to myocarditis, which remain
controversial and ambiguous. Heart rate, as an independent risk factor, has been
shown to be related to cardiac disease. Recent studies also show that the
autonomic nervous system is involved in immunomodulatory myocarditis processes.
Heart rate reduction treatment is recommended in myocarditis based on a number of
animal experiments and clinical trials. It is possible that heart rate-lowering
treatments can help to attenuate the inflammatory response and myocyte injury and
reverse ventricular remodeling. However, how to execute the protective effects of
heart rate reduction on myocarditis is still not clear. In this review, we
discuss the pathogenesis and pathophysiological process of viral myocarditis and
propose heart rate lowering as a therapeutic target for myocarditis, especially
in light of the third-generation beta-blockade carvedilol and funny channel
blocker ivabradine. We also highlight some additional beneficial effects of such
heart rate reduction agents, including anti-inflammatory, antioxidation, anti
nitrosative stress, anti-fibrosis and antiapoptosis properties.
PMID- 29332572
TI - Lipoprotein-associated Phospholipase A2 and Coronary Heart Disease.
AB - In the last decades, the role of inflammation in the pathogenesis of
atherosclerosis has been the topic of intense research. Several markers of
inflammation have shown predictive value for first and recurrent coronary events
in patients without and with established Coronary Heart Disease (CHD). Among
these markers, lipoprotein- associated phospholipase A2 (Lp-PLA2) has recently
received considerable attention. In the present review, the potential role of Lp
PLA2 as a marker of CHD risk and as a therapeutic target is discussed. Elevated
Lp- PLA2 mass and activity appears to be associated with increased risk for CHD,
both in the general population and in patients with established CHD. However, it
is unclear whether the measurement of Lp-PLA2 improves risk discrimination when
incorporated in models that include traditional cardiovascular risk factors.
Moreover, the lack of effect on CHD events of darapladib, a potent, selective Lp
PLA2 inhibitor, in two large, randomized, placebo-controlled trials and the
mostly negative findings of genetic association studies suggest that Lp-PLA2 is
unlikely to represent a causal factor in atherogenesis. Therefore, it is doubtful
whether Lp-PLA2 will constitute a therapeutic target for the prevention of CHD.
PMID- 29332573
TI - Torsades de Pointes in Patients with Polymyalgia Rheumatica.
AB - Polymyalgia rheumatica (PMR) represents the most common inflammatory rheumatic
disease of the elderly. It is characterized by synovitis of proximal joints and
extra-articular synovial structures, along with chronic high-grade systemic
inflammation. PMR is closely related to giant cell arteritis (GCA), a large
vessel vasculitis that involves the major branches of the aorta, particularly the
extracranial branches of carotid artery including temporal arteries. It is
currently believed that PMR and GCA may represent different manifestations of the
same disease process. Chronic systemic inflammation is presently recognized as
one of the key pathogenic mechanisms underlying cardiovascular disease and
associated complications, including cardiac arrhythmias and sudden death. In this
regard, several studies demonstrated that besides promoting structural heart
disease, inflammatory activation may also be per se arrhythmogenic, via cytokine
mediated effects on cardiac electrophysiology. In particular, increasing evidence
points to inflammation as a novel risk factor for QTc prolongation and related
life-threatening arrhythmias, specifically Torsade de Pointes (TdP). Starting
from the report of two cases of TdP occurring in PMR patients with active disease
and elevated circulating IL-6 levels, we here reviewed literature data regarding
heart involvement and arrhythmic events in PMR/GCA, as well as TdP risk in
inflammatory diseases. Potential underlying mechanisms were dissected, by
focusing on the driving role of inflammatory activation.
PMID- 29332574
TI - Biomacromolecular Based Fibers in Nanomedicine: A Combination of Drug Delivery
and Tissue Engineering.
AB - BACKGROUND: Biopolymers based materials (polysaccharides, lipids, proteins, and
nucleic acids) are one of the basic resources in bio-engineering sciences because
of desirable features. Moreover, nanobiotechnology innovates nanomaterial and
associated technique in nano medicine (drug delivery and tissue engineering).
METHODS: In the nano-medicine, fibers are introduced as a successful biomimetic
extracellular matrix scaffolds and drug carrier systems. Electrospinning as a
simple and cost-effective technique is used to design nanofibers. Natural
polymers including chitosan, alginic acid, hyaluronic acid, collagen, gelatin,
and albumin are excellent candidates for electrospinning. However, these types of
biopolymers typically have difficulty in electrospinning. RESULTS: Therefore, for
spinning of these polymers, the condition of the procedure including solvent,
copolymer addition, cross-linker addition, and optimization of spinning should be
done. CONCLUSION: The present study gathered information about fiber-based
nanodevices from biopolymers in a drug transportation or tissue engineering.
PMID- 29332576
TI - Current Understanding of Physicochemical Mechanisms for Cell Membrane Penetration
of Arginine-rich Cell Penetrating Peptides: Role of Glycosaminoglycan
Interactions.
AB - Arginine-rich cell penetrating peptides (CPPs) are very promising drug carriers
to deliver membrane-impermeable pharmaceuticals, such as siRNA, bioactive
peptides and proteins. CPPs directly penetrate into cells across cell membranes
via a spontaneous energy-independent process, in which CPPs appear to interact
with acidic lipids in the outer leaflet of the cell membrane. However, acidic
lipids represent only 10 to 20% of the total membrane lipid content and in
mammalian cell membranes they are predominantly located in the inner leaflet.
Alternatively, CPPs favorably bind in a charge density- dependent manner to
negatively charged, sulfated glycosaminoglycans (GAGs), such as heparan sulfate
and chondroitin sulfate, which are abundant on the cell surface and are involved
in many biological functions. We have recently demonstrated that the interaction
of CPPs with sulfated GAGs plays a critical role in their direct cell membrane
penetration: the favorable enthalpy contribution drives the high-affinity binding
of arginine-rich CPPs to sulfated GAGs, initiating an efficient cell membrane
penetration. The favorable enthalpy gain is presumably mainly derived from a
unique property of the guanidino group of arginine residues forming multidentate
hydrogen bonding with sulfate and carboxylate groups in GAGs. Such interactions
can be accompanied with charge neutralization of arginine-rich CPPs, promoting
their partition into cell membranes. This review summarizes the current
understanding of the physicochemical mechanism for lipid membrane penetration of
CPPs, and discusses the role of the GAG interactions on the cell membrane
penetration of CPPs.
PMID- 29332575
TI - Protective Role of Italian Juglans regia L. nut Ethanolic Extract in Human
Keratinocytes under Oxidative and Inflammatory Stress.
AB - OBJECTIVE: In this research, fatty acid profile and polyphenolic content of an
ethanolic extract of walnut from Juglans regia L. collected in Central Italy,
were characterized. The potential antioxidant and anti-inflammatory effects of
the extract were investigated in the human keratinocytes cell line. METHODS:
Fatty acid profile was determined by gas chromatography/mass spectrometry
analysis, total phenolic content by Folin-Ciocalteu method and aluminum chloride
colorimetric method was used for determination of total flavonoids.
Kertatinocytes were exposed to t-butyl hydroperoxide or Tumor Necrosis Factor
alfa in the absence or presence of extract. Reduced glutathione was determined by
Sedlak method; lipid peroxidation was assessed by measuring thiobarbituric acid
reactive substances. t-butyl hydroperoxide and Tumor Necrosis Factor alfa-induced
intracellular reactive oxygen species were monitored by fluorescent probes. The
expression of some genes related to the inflammatory process (IL-6, IL-8, ikB,
and ICAM) were analysed by Real-time PCR. RESULTS: JRE contains a favourable
fatty acid profile with low saturated fats (19%) and high-unsaturated fats (81%)
with a prevalence of the omega-6 linoleic acid (48%). Also a significant amount
of polyphenols was found (5,0052 mg gallic acid equivalent/gdw). Antioxidant and
anti-inflammatory properties of JRE were observed on analysed cellular model. JRE
antioxidants counteracted ROS production, GSH depletion and lipid peroxidation as
well downregulated the expression of some genes related to the inflammatory
process. Moreover, polyunsaturated fatty acids exhibited anti-inflammatory
properties. CONCLUSION: The obtained results uphold walnut as dietary adjunct in
health promotion and drive towards its development in drug therapy against
chronic inflammatory disorders, including inflammatory skin diseases.
PMID- 29332577
TI - The Potential Use of Peptides in Cancer Treatment.
AB - Conventional chemotherapeutic drugs have significant limitations. For example,
tumors may develop resistance, cancers may relapse after treatment, and the drugs
may induce secondary malignancies in the treatment of metastatic cancer. There is
still a great need for drugs that are able to destroy cancer cells selectively,
that is, to effectively treat slow-growing and dormant cells without being
affected by chemoresistance mechanisms. A growing number of studies indicate that
peptides may be beneficial for drug discovery and development. Peptides offer
minimal immunogenicity, excellent tissue penetrability, low-cost
manufacturability, and ease of modification for enhancing in vivo stability and
biological activity, properties which make them ideal candidates for cancer
treatment. This review highlights recent advances in and future prospects for the
application of peptides as therapeutic agents for cancer therapy. We discuss the
application of peptides in cancer therapy, alone and in combination with other
peptides or small-molecule chemotherapeutic drugs, for use in targeted cancer
therapy. Furthermore, we consider the use of peptides as a carrier for targeted
molecular imaging in the diagnosis and follow-up treatment of cancer. This
account also reviews the challenges of using peptide drugs and ways to overcome
these limitations. The results obtained in studies presented in this paper
indicate that peptides are promising candidates for targeted cancer therapy.
PMID- 29332578
TI - Amyloid-beta Inhibits PDGFbeta Receptor Activation and Prevents PDGF-BBInduced
Neuroprotection.
AB - BACKGROUND: PDGFbeta receptors and their ligand, PDGF-BB, are upregulated in vivo
after neuronal insults such as ischemia. When applied exogenously, PDGF-BB is
neuroprotective against excitotoxicity and HIV proteins. OBJECTIVE: Given this
growth factor's neuroprotective ability, we sought to determine if PDGF-BB would
be neuroprotective against amyloid-beta (1-42), one of the pathological agents
associated with Alzheimer's disease (AD). METHODS AND RESULTS: In both primary
hippocampal neurons and the human-derived neuroblastoma cell line, SH-SY5Y,
amyloid-beta treatment for 24 h decreased surviving cell number in a
concentrationdependent manner. Pretreatment with PDGF-BB failed to provide any
neuroprotection against amyloid-beta in primary neurons and only very limited
protective effects in SH-SY5Y cells. In addition to its neuroprotective action,
PDGF promotes cell growth and division in several systems, and the application of
PDGFBB alone to serum-starved SH-SY5Y cells resulted in an increase in cell
number. Amyloid-beta attenuated the mitogenic effects of PDGF-BB, inhibited PDGF
BB-induced PDGFbeta receptor phosphorylation, and attenuated the ability of PDGF
BB to protect neurons against NMDA-induced excitotoxicity. Despite the ability of
amyloid-beta to inhibit PDGFbeta receptor activation, immunoprecipitation
experiments failed to detect a physical interaction between amyloid-beta and PDGF
BB or the PDGFbeta receptor. However, G protein-coupled receptor transactivation
of the PDGFbeta receptor (an exclusively intracellular signaling pathway)
remained unaffected by the presence of amyloid-beta. CONCLUSIONS: As the PDGF
system is upregulated upon neuronal damage, the ability of amyloid-beta to
inhibit this endogenous neuroprotective system should be further investigated in
the context of AD pathophysiology.
PMID- 29332579
TI - Alzheimer's Disease: A Systemic Review of Substantial Therapeutic Targets and the
Leading Multi-functional Molecules.
AB - Alzheimer's Disease (AD) is a fatal neurodegenerative disorder, having a complex
aetiology with numerous possible drug targets. There are targets that have been
known for years while more new targets and theories have also emerged. Beta
amyloid and cholinesterases are the most significant biological targets for
finding curative treatment of AD. The major class of drugs used for AD till now
has been the Cholinesterase (ChE) inhibitors. Other prevailing models of
molecular pathogenesis in AD include Neurofibrillary Tangles (NFTs) and amyloid
deposition, tryptophan degradation pathway, kinase and phosphatase activity
imbalance and neuroinflammation. The beta amyloid aggregation initiates flow of
events resulting in neurotoxicity and finally clinical pathogenesis of AD.
Furthermore, ApoE is another very significant entity involved in repairing and
maintaining the neurons and has important role in neurodegeneration.
Neuroinflammation being the primmest symptom for AD is essential to focus on.
Multiple factors and complexity in interlinking disease progression pose huge
challenge to find one complete curing drug. With so many promising molecules
having multiform pharmacological profile from all over the world however facing
failures in clinical trials indicates the need to consider all aspects of the old
as well as new therapeutic targets of AD. Until the disease mechanism is better
understood, it is likely that multiple targeting, symptomatic and
diseasemodifying, is the way forward. Most recent approaches to find anti
Alzheimer's agents have focused on multi-target directed agents that include
targeting all glorious targets hypothesized against AD. New identification of
prototype candidates that could be starting point of a new way of thinking drug
design has been done and many drug candidates are under preclinical evaluation.
The main focus of this review is to discuss the recent understanding of key
targets and the development of potential therapeutic agents for the treatment of
AD. It also documents the current therapeutic agents in clinical trials and under
development based on their main mode of action.
PMID- 29332580
TI - Aurora Kinase Inhibitors in Head and Neck Cancer.
AB - Aurora kinases are a group of serine/threonine kinases responsible for the
regulation of mitosis. In recent years, with the increase in Aurora kinase
related research, the important role of Aurora kinases in tumorigenesis has been
gradually recognized. Aurora kinases have been regarded as a new target for
cancer therapy, resulting in the development of Aurora kinase inhibitors. The
study and application of these small-molecule inhibitors, especially in
combination with chemotherapy drugs, represent a new direction in cancer
treatment. This paper reviews studies on Aurora kinases from recent years,
including studies of their biological function, their relationship with tumor
progression, and their inhibitors.
PMID- 29332581
TI - Cetuximab and the Head and Neck Squamous Cell Cancer.
AB - The Head and Neck Squamous Cell Cancer (HNSCC) is the most common type of head
and neck cancer (more than 90%), and all over the world more than a half million
people have been developing this cancer in the last years. This type of cancer is
usually marked by a poor prognosis with a really significant morbidity and
mortality. Cetuximab received early favor as an exciting and promising new
therapy with relatively mild side effect, and due to this, received authorization
in 2004 from the European Medicines Agency (EMA) and in 2006 from the Food and
Drug Association (FDA) for the treatment of patients with squamous cell cancer of
the head and neck in combination with radiation therapy for locally advanced
disease. In this work we will review the application and the efficacy of the
Cetuximab in the treatment of the HNSCC.
PMID- 29332582
TI - Dual BACE-1/GSK-3beta Inhibitors to Combat Alzheimer's Disease: A Focused Review.
AB - In industrialized countries, Alzheimer's disease represents the most devastating
neurodegenerative disorder in elderly people and the search for a disease
modifying agent is still justified by this unmet need. Several possible targets
have been explored to find an appropriate drug therapy, and in this review, dual
inhibitors of beta secretase and glycogen synthase kinase 3, recently reported in
literature, will be appraised. Applying a ligand-based approach, the triazinone
core emerged as a suitable scaffold to simultaneously bind the aspartic dyad of
BACE-1 and the ATP site of GSK-3beta, leading to a series of small molecules
endowed with a balanced micromolar affinity and a promising pharmacokinetic
profile. Differently, by means of a structure-based approach, a series of well
balanced dual binding molecules were designed, taking advantage of the
versatility of the curcumin scaffold. For some of these new compounds a potential
neuroprotective effect was also observed, due to their ability to counteract the
oxidative stress through the inhibition of NQO1 enzyme. Finally, different
virtual screening analyses were performed, leading to the identification of new
potential scaffolds deserving further development.
PMID- 29332583
TI - Eating Green: Shining Light on the Use of Dietary Phytochemicals as a Modern
Approach in the Prevention and Treatment of Head and Neck Cancers.
AB - Enthusiasm for the use of dietary bioactive compounds as chemopreventive agents
and adjuvants for current therapies has increased laboratory research conducted
on several types of cancers including Head and Neck Squamous Cell Carcinoma
(HNSCC). The green chemoprevention movement is a modern approach to highlight
healthy lifestyle changes that aim to decrease the incidence of HNSCC. A healthy
diet can be an effective way to prevent the development of oral cancers.
Discovery of the naturally occurring plant based compounds called phytochemicals
has facilitated the development of new treatment strategies for patients that are
at risk for, or have developed HNSCC. Many of these compounds have been shown to
elicit very potent anti-carcinogenic properties. While there are many compounds
that have been studied, the compounds from two specific categories of
phytochemicals, phenolics (resveratrol, EGCG, curcumin, quercetin, and honokiol)
and glucosinolates (sulforaphane, PEITC and BITC), are emerging as potent and
effective inhibitors of oral carcinogenesis. These compounds have been shown to
inhibit HNSCC growth through a variety of mechanisms. Research has demonstrated
that these compounds can regulate cancer cell proliferation through the
regulation of multiple cell signaling pathways. They can impede cell cycle
progression, induce differentiation and apoptosis, prevent angiogenesis, and
inhibit cancer cell invasive and metastatic properties. They can protect normal
cells during treatment and reduce the damage caused by chemotherapy and
radiotherapy. This review aims to provide an overview of some of the most
effective phytochemicals that have the potential to successfully prevent and
treat head and neck squamous cell carcinoma.
PMID- 29332584
TI - Multicomponent Reactions for Multitargeted Compounds for Alzheimer's Disease.
AB - Alzheimer's Disease (AD) is a multifactorial and fatal neurodegenerative disorder
affecting around 35 million people worldwide, which is characterized by decline
of cholinergic function, deregulation of amyloid beta (Abeta) oligomers formation
and Abeta fibril deposition. Multi-Target- Directed Ligands (MTDLs) have emerged
as an original strategy for developing new therapeutic agents on AD.
Multicomponent Reactions (MCRs) are a useful alternative to sequential multistep
syntheses, allowing scaffold diversity and a rapid and easy access to
biologically relevant compounds. The biological diversity of MCRs is very rich
providing great possibilities for researchers interested in bioactive small
molecular weight compounds. Since the MTDL strategy has been used to develop
compounds endowed with the capacity to interact with different targets, versatile
compound libraries may be obtained by MCRs according to the well established
features of each target. Thus, either MTDLs or monotarget compounds have been
developed by MCRs to address different factors implicated in AD. This work
focuses on antioxidants, calcium channel modulators, both AChE and BuChE
inhibitors, BACE1 inhibitors, and modulators of the nuclear factor (erythroid
derived 2)-like 2. First, we discuss the Biginelli reaction and its use for
developing new interesting compounds for AD, followed by the contribution of Ugi
reaction and, finally, the interest of other MCRs in the same topic.
PMID- 29332585
TI - New Tacrines as Anti-Alzheimer's Disease Agents. The (Benzo)Chromeno-
PyranoTacrines.
AB - Tacrine was the first drug approved by FDA (US) for the treatment of Alzheimer's
disease suffering patients. Nowadays, this agent has been withdrawn from the
clinics due to secondary effects, which, most importantly, include
hepatotoxicity. However, the research on new tacrine analogues devoid of these
therapeutically undesirable effects, but benefiting of their high and well known
positive cholinergic power, has produced a number of new non-hepatotoxic
tacrines. In this context, our laboratory has recently prepared a new set of
heterocyclic tacrines by changing the benzene ring present in tacrine by
appropriate heterocyclic motifs. Based on this approach, in this review we
summarize the results that we have found in the ChromenoPyranoTacrines, one of
the families of tacrine analogues. This highlights their pharmacological profile,
such as their cholinesterase inhibition power, calcium channel blockade,
antioxidant capacity, Abeta-anti-aggregating, and neuroprotective properties. As
a result of this work we have identified permeable, neuroprotective MTD tacrines
racemic hit-tacrines 11-amino-12-(3,4,5-trimethoxyphenyl)-7,9,10,12-tetrahydro-8H
chromeno[2,3- b]quinolin-3-ol (6g) and 14-(3,4-dimethoxyphenyl)-9,11,12,14
tetrahydro-10H-benzo[5,6] chromeno [2,3-b] quinolin-13-amine (7i),devoid of toxic
effects and showing potent anti-cholinesterasic properties, that deserve
attention and further development in order to find new, and more efficient drugs,
for AD therapy.
PMID- 29332586
TI - Recent Developments on Multi-Target-Directed Tacrines for Alzheimer's Disease. I.
The Pyranotacrines.
AB - Tacrine was the first drug to display beneficial effects on cognitive impairment
of Alzheimer Disease (AD) patients. Unfortunately, many treated patients
displayed related hepatotoxicity, and hence this drug was withdrawn.
Notwithstanding, recent efforts have been directed to design small tacrine
analogues targeting the underlying pathogenic mechanisms of AD. In this context,
we have developed a number of pyranotacrines by changing the benzene fused ring
in tacrine by a 4Hpyran. Based on this strategy, in this account we will show the
tacrine analogues that we have designed, synthesized and evaluated as potential
multipotent agents for AD in the last years. We have demonstrated that this
approach is possible, and that a number of readily available tacrine analogues
show cholinesterase inhibition power, as well as other pharmacological
properties, such as calcium channel blockade, antioxidant properties,
neuroprotection, Abeta-amyloid inhibition aggregation capacity, etc., making them
suitable multipotent molecules for further development for the potential
treatment of AD.
PMID- 29332587
TI - Lysosomal Acid Lipase Deficiency: Could Dyslipidemia Drive the Diagnosis?
AB - LAL-deficiency (LAL-D) is a rare and systemic condition, secondary to LIPA gene
mutations, responsible for lysosomal accumulation of cholesteryl esters and
triglycerides, whose manifestations are very heterogeneous in terms of the age of
onset, severity and the type of clinical and radiological manifestations.
Dyslipidemia, hepatomegaly and hepatosteatosis with increased levels of
transaminases are the most common features. The increased risk of premature
atherosclerosis and cardiovascular disorders, secondary to a generalized
alteration of lipid profile and lipoprotein dysfunction associated with LAL-D,
has been increasingly pointed out. Therefore, medical awareness towards LAL
deficiency should be increased, since this condition has to be considered in the
differential diagnosis of pediatric conditions manifested with dyslipidemia and
hepatic accumulation of intracellular products. On the other hand, early patient
identification and management remain challenging.
PMID- 29332588
TI - Treatment Strategies for Hypercholesterolemia.
AB - BACKGROUND: Atherosclerotic disease is a leading cause of morbidity and mortality
in adults and is generally thought of as only affecting adults. However, the
pathologic changes in vessels leading to atherosclerosis, and an increased risk
of cardiovascular disease, have been shown to begin in early adolescence.
OBJECTIVES: There is a growing body of literature suggesting that earlier
treatment, through lifestyle changes and pharmacotherapy, can help reduce this
risk. A growing number of children are presenting with elevated cholesterol
because of the increased prevalence of obesity and diabetes mellitus. METHODS: In
addition, an increasing number of children are living with previously fatal
diseases that increase the risk of atherosclerosis, either because of the disease
process or as adverse effect of the treatment, such as human immunodeficiency
virus, Kawasaki disease, and cardiac transplantation. RESULT AND CONCLUSION: In
addition, specific disorders of cholesterol metabolism, such as Familial
Hypercholesterolemia (FH) may be encountered in a pediatric practice.
PMID- 29332589
TI - Validation of an Arabic Version of the Obesity-Related Wellbeing (ORWELL 97)
Questionnaire in Adults with Obesity.
AB - BACKGROUND: No specific questionnaire that evaluates Health-Related Quality Of
Life (HRQOL) in individuals with obesity is available in the Arabic language. The
aim of this study was therefore to propose and examine the validity and
reliability of an Arabic language version of the ORWELL 97, a validated obesity
related HRQOL questionnaire. METHODS: The ORWELL 97 questionnaire was translated
from English to Arabic language and administered to 318 Arabic-speaking
participants (106 from clinical and 212 from community samples), and underwent
internal consistency, test-retest reliability, construct and discriminative
validity analysis. RESULTS: Internal consistency and the test-retest reliability
were excellent for ORWELL 97 global scores in the clinical sample. Participants
with obesity displayed significantly higher ORWELL 97 scores than participants
from the community sample, confirming the good discriminant validity of the
questionnaire. Confirmatory factor analysis in the clinical sample revealed a
good fit for a modified two-factor structure. CONCLUSION: Overall, the Arabic
version of the ORWELL 97 can be considered validated in Arabic adult patients
with obesity, paving the way to further assessment of its responsiveness in
measuring changes in health-related quality of life associated with obesity
treatment.
PMID- 29332590
TI - Oxidative Stress and Cardiac Remodeling: An Updated Edge.
AB - BACKGROUND: A common phenotype associated with heart failure is the development
of cardiac hypertrophy. Cardiac hypertrophy occurs in response to stress, such as
hypertension, coronary vascular disease, or myocardial infarction. The most
critical pathophysiological conditions involved may include dilated hypertrophy,
fibrosis and contractile malfunction. The intricate pathophysiological mechanisms
of cardiac hypertrophy have been the core of several scientific studies, which
may help in opening a new avenue in preventive and curative procedures.
OBJECTIVES: To our knowledge from the literature, the development of cardiac
remodeling and hypertrophy is multifactorial. Thus, in this review, we will focus
and summarize the potential role of oxidative stress in cardiac hypertrophy
development. CONCLUSION: Oxidative stress is considered a major stimulant for the
signal transduction in cardiac cells pathological conditions, including
inflammatory cytokines, and MAP kinase. The understanding of the
pathophysiological mechanisms which are involved in cardiac hypertrophy and
remodeling process is crucial for the development of new therapeutic plans,
especially that the mortality rates related to cardiac remodeling/dysfunction
remain high.
PMID- 29332591
TI - Anti-Trypanosoma cruzi Activity in vitro of Phases and Isolated Compounds from
Excoecaria lucida Leaves.
AB - BACKGROUND: Chagas disease is caused by the protozoan parasite Trypanosoma cruzi.
This illness is found mainly in 21 Latin American countries and an estimated 8
million people are infected worldwide. The unsatisfactory chemotherapy provokes
severe toxicity and resistant strains. Medicinal plants constitute a promising
source of new drugs and remedies against all kinds of disorders, mainly
infectious diseases arousing interest worldwide. OBJECTIVE: The aim of this study
is the isolation, structural identification and evaluation of the trypanocidal
activity of samples present in the Excoecaria lucida Sw. leaves. METHODS: Total
extract (TE) of E. lucida Sw. leaves was obtained by ethanol extract therefore
fractionated sequentially with hexane, ethyl acetate and n-butanol, to obtain
three phases: Hex, EA and But, respectively. Ellagic acid (EL1) was purified from
both EA and But phases, while EL2; a 1:1 stigmasterol-3-O-beta-D-glucopyranoside
plus sitosterol-3-O-beta-D-glucopyranoside mixture was obtained from the Hex
phase. Activity assays were performed using bloodstream and intracellular forms
of T. cruzi and cytotoxicity assays using L929 fibroblasts. RESULTS: The EL1 and
EL2 samples were more active against bloodstream trypomastigote forms with EC50
of 53.0+/-3.6 and 58.2+/-29.0 ug/mL, respectively; at 100 ug/mL. These samples
also showed 70% of inhibition of L929 cells infection. Toxicity assays
demonstrated that after 96 h of treatment only the fractions Hex and EA presented
detectable cytotoxicity. CONCLUSION: Ellagic acid, stigmasterol-3-O-beta-D
glucopyranoside and sitosterol-3-O-beta-Dglucopyranoside are reported for the
first time in E. lucida Sw. leaves as well as their biological activity studies
supporting further investigations for Chagas disease treatment.
PMID- 29332592
TI - Construction of an M1GS Ribozyme for Targeted and Rapid mRNA Cleavage;
Application on the Ets-2 Oncogene.
AB - BACKGROUND: RNase P-mediated cleavage of target RNAs has been proposed as a
promising tool for gene silencing. Ets-2 proto-oncogene controls the expression
of a wide variety of genes involved in cancer and immunity. OBJECTIVE:
Construction of a functional RNase P-based ribozyme (M1GS303) that targets Ets-2
mRNA. METHODS: The accessible sites for targeting of Ets-2 mRNA were identified
by footprinting analysis. M1GS303 ribozyme was constructed by cloning. The
activity of the ribozyme in the presence or absence of spiramysin in E. coli
cells and human cell lines was quantified by RT-PCR. The efficiency of the
ribozyme in silencing the endogenous expression of Ets-2 in human cell lines was
examined by RT-PCR, western blot and immunofluorescence analysis. RESULTS: In E.
coli cells co-transformed with plasmids bearing M1GS303 and the ets-2 target
gene, Ets-2 mRNA was decreased by 93% 12h after IPTG induction in the absence,
and after 4h in the presence of spiramycin. Ets-2 was rapidly downregulated in
the human embryonic kidney cell line HEK293 and the T-cell line Jurkat
transfected with an M1GS303 plasmid; the silencing effect of M1GS303 was
considerably faster when the cells were cultured with spiramycin. In Jurkat
cells, Ets-2-downregulation resulted in upregulation of the expression of IL-2,
IL-4 and IFN-alpha cytokine genes that have Ets-2 binding sites on their
promoters, whereas it had no effect on the expression of the IL-10 gene that
lacks Ets-2 binding sites on its promoter. CONCLUSIONS: M1GS303 ribozyme cleaves
effectively Ets-2 mRNA in bacteria and mammalian cells, and its activity is
enhanced by spiramycin. Downregulation of ets-2 gene in the T-cell line Jurkat
upregulates IL-2, IL-4 and IFN-alpha cytokine genes. M1GS technology may be a
better alternative to conventional gene-interference therapies and the
delineation of the effects of gene silencing in various pathologies.
PMID- 29332593
TI - Facile Synthesis, Crystal Structure, DFT Calculation and Biological Activities of
4-(2-fluorophenyl)-3-(3-methoxybenzyl)-1H-1,2,4-triazol-5 (4H)-one (5).
AB - BACKGROUND: In the past few decades, design, synthesis, and characterization of
novel heterocyclic compounds with auspicious biological profile received the
considerable attention of the scientific community. Among them, the small and
simple organic molecular backbone like triazole moiety have a broad spectrum of
applications in the medicinal as well as diagnostic areas. OBJECTIVE: The
objective of present study was synthesis, characterization, and exploration of
biological profile of 4-(2-fluorophenyl)-3-(3-methoxybenzyl)-1H-1,2,4-triazole
5(4H)-one (5). The tautomeric interconversion of the molecule was observed by the
single crystal XRD and DFT analysis. METHODS: N-(2-fluorophenyl)-2-[2-(3
methoxyphenyl)acetyl]hydrazine carboxamide (4) was synthesized by the
condensation of 2-(3-methoxyphenyl)acetohydrazide (3) with 1-fluoro-2-
isocyanatobenzene. The dehydrocyclization of compound (4) yielded target compound
(5) by refluxing in 2 N aqueous sodium hydroxide solutions. The target molecule
was characterized by FTIR, 1H NMR, 13C NMR, single crystal X-ray diffraction
analysis and DFT calculation. The enzymatic assay measurements were carried out
by using a microplate reader (OPTI Max, Tunable Microplate Reader; Wavelength
range: 340-850 nm; for 96-well plates) while DFT calculation was performed by
Gaussian 09 package. RESULTS: The XRD result and DFT calculations showed that
molecule 5 predominantly exists in thione conformation and crystallized in the
triclinic system of P-1 space group. Furthermore, for the practical applicability
of synthesized compound 5, the in vitro acetylcholinesterase as well as alpha
glucosidase inhibition activities were performed and found moderate enzyme
inhibition potential comparable with that of reference inhibitors. CONCLUSION:
This study might be helpful for future design and development of potent enzyme
inhibitor to control Alzheimer's as well as diabetic disease. The DFT and single
crystal XRD analysis data might be helpful for understanding the mechanism of
drug binding and its mode of action.
PMID- 29332595
TI - New Bis-Pyrazolones as Potential Leads for ROS Inhibition; Environment Friendly
Green Synthesis, Structural Characterization, and In Vitro Studies.
AB - BACKGROUND: Pyrazolones have identified as significant antioxidant agents and
many marketed and clinically prescribed NSAIDs have pyrazolone ring as main
scaffold. METHOD: Keeping in consideration the antioxidant potential of
pyrazolone scaffold, new bispyrazolones 3-30 were synthesized by a green and
enviroment friendly reaction route, in which two equivalents of 1-(4
chlorophenyl)-3-methyl-1H-pyrazol-5-ol were treated with one equivalent of
benzaldehyde derivatives without any catalyst. All compounds were structurally
characterzied by 1H-NMR and FAB analysis. 13C-NMR of selected compounds was also
recorded. All compounds gave satisfactory elemental analyses and found in good
agreement with calculated values. RESULTS: Synthetic bis-pyrazolones 3-30 were
evaluated for their oxidative burst inhibitory effect of zymosan stimulated whole
blood phagocytes by using luminol enhanced chemilluminescence technique. All
molecules demonstrated the potent ROS inhibition activity in the range of IC50 =
1.2 +/- 0.1-48.8 +/- 3.9 uM as compared to the standard ibuprofen (IC50 = 54.2 +/
9.2 MUM). The purity of active compounds was checked by HPLC. CONCLUSION: This
study has identified a number of non-acidic lead molecules for future research on
ROS inhibitors.
PMID- 29332594
TI - In vitro and in silico Evaluation of Non-Quaternary Reactivators of AChE as
Antidotes of Organophosphorus Poisoning - a New Hope or a Blind Alley?
AB - BACKGROUND: In the last decade, the concept of uncharged reactivators potentially
able to penetrate the CNS has been introduced as an alternative to the classic
charged oxime reactivators. However, this concept brings with it several
associated drawbacks such as higher lipophilicity, difficulty in administration,
lower affinity to cholinesterases, and higher toxicity risk. OBJECTIVE: In this
study, we compare data obtained for a set of five classic charged reactivators
and a set of three recently published uncharged oximes supplemented by two novel
ones. METHODS: This time, we used only in silico prediction and in vitro
approaches. RESULTS: Our data showed that tested uncharged oximes have low
affinity for cholinesterases, do not possess high reactivation potency, and
certainly represent a greater toxicity risk due to higher lipophilicity. We
assume that balanced physicochemical properties will be required for the
successful treatment of OP poisoning. Nevertheless, the compound meeting such
criteria and pinpointed in silico (K1280) failed in this particular case.
CONCLUSION: From the presented data, it seems that the concept of uncharged
reactivators will have to be modified, at least to improve the bioavailability
and to satisfy requirements for in vivo administration.
PMID- 29332596
TI - Synthesis of Thiocarbohydrazones and Evaluation of their in vitro Antileishmanial
Activity.
AB - BACKGROUND: Leishmaniasis is a protozoan parasitic vector-borne disease which is
endemic in 88 tropical countries. Infected sandfly is the main vector of this
disease, while there are several other vectors, parasites, and reservoirs
involved in the transmission of this disease. Leishmania donovani, L. infantum,
and L. chagasi are common disease causing species, transmitted through sandflies.
Leishmaniasis is a neglected tropical disease with broad spectrum of clinical
manifestations. Cutaneous leishmaniasis is prevalent in many countries, including
Pakistan. METHODS: Thiocarbohydrazones (1-20) were synthesized through one pot
method by refluxing thiocarbahydrazide with different substituted benzaldehydes
in ethanol in the presence of acetic acid as a catalyst. These synthetic
compounds were evaluated for their potential antileishmanial activity in vitro
against Leishmania major promastigotes. RESULTS: Compounds 5-8, 11, 14, 16, 17,
19 and 20 were reported earlier, while compounds 2-4, 9, 10, 12, 13 and 15 were
identified as were derivatives. Compounds 1-20 demonstrated antileishmanial
activities with IC50 values between 1.63 +/- 0.05 - 64.82 +/- 0.17 uM, as
compared to the standard drug pentamidine (IC50 = 5.09 +/- 0.04 uM). Compounds 2
(IC50 = 1.63 +/- 0.05 uM), 11 (IC50 = 2.33 +/- 0.01 uM), 4 (IC50 = 11.03 +/- 0.20
uM), and 10 (IC50 = 11.63 +/- 0.06 uM) displayed comparable antileishmanial
activities to the standard drug pentamidine. However, compounds 13, 15-17, and 20
with IC50 values 36.95 +/- 0.025, 64.82 +/- 0.17, 64.27 +/- 0.38, 62.34 +/- 0.38,
and 40.47 +/- 0.05 uM, respectively, showed a moderate antileishmanial activity.
In contrast, compounds 1, 3, 5-9, 12, 14, 18, and 19 demonstrated less than 50%
growth inhibition of promestigotes of L. major, and thus considered as inactive.
CONCLUSION: In thiocarbohydrazone derivatives, different substituents at aryl
part may be responsible for a varying degree of antileishmanial activity in
vitro. Consequently, these compounds might have a potential for further studies
as a new class of antileishmanial agents.
PMID- 29332597
TI - Synthesis of a Novel Class of 1,3-oxathiolane Nucleoside Derivatives of T- 705
and Evaluation of Their Anti-influenza A Virus and Anti-HIV Activity.
AB - BACKGROUND: T-705 (Favipiravir) is a broad spectrum antiviral agent approved for
stockpiling in Japan and currently in Phase 3 testing in the United States.
Against influenza, it acts as a prodrug, converted intracellularly to selectively
inhibit viral RNA-dependent RNA polymerase or similar enzymes. This is regarded
as a novel antiviral mechanism of action, reducing crossresistance to other
existing anti-influenza drugs. OBJECTIVE: To develop new analogs, a class of 1,3
oxathiolane nucleoside derivatives of T-705 was designed and synthesized in this
work. RESULTS: Anti-influenza activity and Anti-HIV activity of these compounds
were evaluated. Compound 1a displayed activity against A H1N1 with an IC50 of
40.4 umol/L. Compound 1b showed weak activity against HIV with a viral
suppression rate of 70-80% at 30 umol/L. CONCLUSION: A class of 1,3-oxathiolane
nucleoside derivatives of T-705 was designed and synthesized, and one of them was
identified as a novel scaffold against viral infection.
PMID- 29332598
TI - Synthesis of New Isoxazole-, Pyridazine-, Pyrimidopyrazines and Their Anti
Inflammatory and Analgesic Activity.
AB - BACKGROUND: Isoxazoles, pyridazines, and pyrimidopyrazines have recently
attracted attention due to their potent pharmacological activities. They
exhibited anticancer, neuroprotective, analgesic and anti-inflammatory effects.
OBJECTIVE: The study aimed to synthesize novel isoxazoles, pyridazines, and
pyrimidopyrazines through efficient high yield protocol for evaluating their
analgesics and anti-inflammatory activities. METHOD: A series of novel isoxazole
, pyridazine-, pyrimidopyrazine derivatives was prepared from 5,8-alkyl-1,3
dimethyl-5,6-dihydropyrimido[5,6-e]pyrazine-2,4,7-trione (1a,b) as the starting
material. RESULTS: The prepared derivatives were synthesized in moderate to good
yields (60-75%) in a stepwise efficient protocol under mild condition. These new
compounds have been proven by several spectroscopic techniques as IR, 1D and 2D
NMR techniques and mass analysis. The in vivo anti-inflammatory was assessed for
the synthesized compounds using carrageenan-induced rat hind paw edema model.
Also, the in vivo analgesic activity for these products was examined utilizing
hot-plate and acetic acid-induced writhing response assays. CONCLUSION: The
isoxazole derivatives (3a-f) showed the most forceful anti-inflammatory and
analgesic activities. Pyrimidopyrazines (4a-f) demonstrated weaker but comparable
antiinflammatory and analgesic activities to the positive controls.
PMID- 29332599
TI - The Synthesis of Chalcones as Anticancer Prodrugs and their Bioactivation in CYP1
Expressing Breast Cancer Cells.
AB - BACKGROUND: Although the expression levels of many P450s differ between tumour
and corresponding normal tissue, CYP1B1 is one of the few CYP subfamilies which
is significantly and consistently overexpressed in tumours. CYP1B1 has been shown
to be active within tumours and is capable of metabolising a structurally diverse
range of anticancer drugs. Because of this, and its role in the activation of
procarcinogens, CYP1B1 is seen as an important target for anticancer drug
development. OBJECTIVE: To synthesise a series of chalcone derivatives based on
the chemopreventative agent DMU-135 and investigate their antiproliferative
activities in human breast cancer cell lines which express CYP1B1 and CYP1A1.
METHOD: A series of chalcones were synthesised in yields of 43-94% using the
Claisen-Schmidt condensation reaction. These were screened using a MTT assay
against a panel of breast cancer cell lines which have been characterised for
CYP1 expression. RESULT: A number of derivatives showed promising
antiproliferative activities in human breast cancer cell lines which express
CYP1B1 and CYP1A1, while showing significantly lower toxicity towards a non
tumour breast cell line with no CYP expression. Experiments using the CYP1
inhibitors acacetin and alpha-naphthoflavone provided supporting evidence for the
involvement of CYP1 enzymes in the bioactivation of these compounds. CONCLUSION:
Chalcones show promise as anticancer agents with evidence suggesting that CYP1
activation of these compounds may be involved.
PMID- 29332600
TI - Finding Novel Anti-carcinomas Compounds by Targeting SFRP4 Through Molecular
Modeling, Docking and Dynamic Simulation Studies.
AB - BACKGROUND: Secreted Frizzled-Related Protein 4 (SFRP4) is a glycoprotein that
acts as a competitor of both canonical and non-canonical Wnt pathways. SFRP4 is
mostly expressed in ovary and plays a significant role as a target molecule to
cure ovarian carcinoma. OBJECTIVE: Multiple chemical agonists are being used to
cure ovary melanoma. We are interested in theoretically analyzing the compounds
through computational approaches for their potential inhibitory effects against
SFRP4. METHODS: Compounds were sketched in Chemsketch drawing tool and minimized
through chimera tool. Because the crystal structure of SFRP4 is not available in
Protein Data Bank, homology modeling approach was used to predict Three
Dimensional (3D) crystal structure of SFRP4. Moreover, multiple computational
approaches such as molecular docking and Molecular Dynamic (MD) simulations along
with various online tools were employed to screen the best inhibitor against
ovary melanoma. RESULTS: The docking results showed that 1d and 1e compounds
revealed significant binding energy values (-9.10 and -9.00 kcal/mol,
respectively) compared with the standard drugs such as cis-platin and docetaxel (
3.30, -10.80 kcal/mol), respectively. Moreover, MD simulation results showed that
1d has little fluctuations throughout the simulation period as depicted by the
root mean square deviation and root mean square fluctuation graphs. CONCLUSION:
The present in-silico study provides a deeper insight into the structural
attributes of 1d compound and its overall molecular interactions against SFRP4
and gives a hypothetical gateway to use this compound as a potential inhibitor
against ovarian carcinoma.
PMID- 29332601
TI - Quantitative Structure-activity Relationship Study of Betulinic Acid Derivatives
Against HIV using SMILES-based Descriptors.
AB - BACKGROUND: Human Immunodeficiency Virus (HIV) is the causative agent of Acquired
Immunodeficiency Syndrome (AIDS) that imposes a global health burden. Therefore,
HIV therapeutic agents have been discovery and development. OBJECTIVE: To
construct Quantitative-structure Activity Relationship (QSAR) models of betulinic
acid derivatives with anti-HIV activity using Simplified Molecular-Input Line
Entry System (SMILES)- based descriptors. METHODS: A data set of 107 betulinic
acid derivatives and their anti-HIV activity was used to develop QSAR models. The
SMILES format of the compounds was employed as descriptors for model construction
using the CORAL software by means of the Monte Carlo method. RESULTS: Constructed
QSAR models provided good correlation coefficients (R2) and root mean square
error (RMSE) with values in the range of 0.5660-0.5890 and 0.963-1.020,
respectively, for the training set, R2 value of 0.7206-0.7837 and RMSE as 0.609
1.250, respectively, for the calibration set, and R2 value of 0.6257-0.7748 and
RMSE as 0.837-0.995, respectively, for the validation set. The best QSAR model
displayed statistical parameters for training set: R2 = 0.5660 and RMSE = 0.963;
calibration set: R2 = 0.7273 and RMSE = 0.609, and validation set: R2 = 0.7748
and RMSE = 0.972. In addition, features of the molecular structure that are
promoters of the endpoint increase and decrease were defined and discussed. These
are the basis for the mechanistic interpretation of the suggested models.
CONCLUSION: These findings provide useful knowledge for guiding the design of
novel compounds with promising anti-HIV activity.
PMID- 29332602
TI - Nanoemulsion Strategy for Ursolic and Oleanic Acids Isolates from Plumeria Obtusa
Improves Antioxidant and Cytotoxic Activity in Melanoma Cells.
AB - BACKGROUND: Triterpenoids are an important class of natural bioactive products
present in many medicinal plants. OBJECTIVE: The aim of present study is to
investigate the antioxidant and anticarcinogenic potential of Oleanolic Acid (OA)
and Ursolic Acid (UA) on B16 murine melanoma cell line isolated from Plumeria
obtusa, free and loaded in a nanoemulsion (NEm) system. METHODS: The nanoemulsion
was characterized by dynamic light scattering, transmission electron microscopy.
The viscosity was also evaluated. The antioxidant activity was determined by the
reduction of 2,2-diphenyl-2- picrylhydrazyl (DPPH) free radical. In vitro
proliferation studies were determined using the sulforhodamine-B method. RESULTS:
OA/UA natural mixture exhibited high percentage of inhibition of DPPH (86.06% and
85.12%, with and without irradiation). Percentages of inhibition higher than 85%
in samples with and without ultraviolet irradiation were recorded when loaded in
the NEm system. The natural mixture incorporated into the NEm showed cytotoxic
activity from 2.9 uM, whereas the free compounds from 17.4 uM. CONCLUSION: We
conclude that these pentacyclic triterpenes loaded in a NEm system could be
considered as a new potential tool for further investigation as anticancer
agents.
PMID- 29332603
TI - Previous use of Statins and Atrial Electrical Remodeling in Patients with
Cryptogenic Stroke.
AB - BACKGROUND: In the general population the leading cause of cardioembolic stroke
is atrial fibrillation (AF). A silent AF is also the possible cause of many
cryptogenic strokes. P wave dispersion (PWD), a predictor of AF, has been
proposed as a marker of silent AF occurrence in these strokes. PWD correlates
with high-sensitive C-reactive protein levels reflecting the role of inflammation
in promoting a slowed and inhomogeneous atrial conduction. Statins have a
multitude of additional effects beyond lipid lowering, in particular anti
inflammatory effects that may influence atrial conduction. OBJECTIVE: The aim of
this study was to evaluate the effects of previous statin use on PWD in patients
with cryptogenic stroke, in order to highlight a possible role for statins in
preventing atrial conduction alterations that predispose to AF. METHOD: We
enrolled 131 patients (67 males, 64 females; mean age 69+/-13 years) with
cryptogenic stroke. All patients underwent neuroimaging examination, arterial
ultrasound examination, echocardiography and ECG. PWD was measured in all
subjects. RESULTS: Patients previously treated with statins (n: 34) had lower PWD
and P index values in comparison with no-statin group (41.7+/-12.2 vs 48.7+/-15.2
ms, p=0.01, and 14.2+/-3.7 vs 16.5+/-5.3 ms, p=0.02, respectively). CONCLUSIONS:
Our results show lower PWD values in cryptogenic stroke patients previously
treated with statins. These findings provide support to the hypothesis that
statins may play a role in modulating atrial electrophysiological and structural
properties, preventing the occurrence of a slowed and heterogeneous atrial
conduction and finally, reducing the occurrence of AF.
PMID- 29332604
TI - The effect of an adenosine A2A agonist on intra-tumoral concentrations of
temozolomide in patients with recurrent glioblastoma.
AB - BACKGROUND: The blood-brain barrier (BBB) severely limits the entry of
systemically administered drugs including chemotherapy to the brain. In rodents,
regadenoson activation of adenosine A2A receptors causes transient BBB disruption
and increased drug concentrations in normal brain. This study was conducted to
evaluate if activation of A2A receptors would increase intra-tumoral temozolomide
concentrations in patients with glioblastoma. METHODS: Patients scheduled for a
clinically indicated surgery for recurrent glioblastoma were eligible.
Microdialysis catheters (MDC) were placed intraoperatively, and the positions
were documented radiographically. On post-operative day #1, patients received
oral temozolomide (150 mg/m2). On day #2, 60 min after oral temozolomide,
patients received one intravenous dose of regadenoson (0.4 mg). Blood and MDC
samples were collected to determine temozolomide concentrations. RESULTS: Six
patients were enrolled. Five patients had no complications from the MDC placement
or regadenoson and had successful collection of blood and dialysate samples. The
mean plasma AUC was 16.4 +/- 1.4 h ug/ml for temozolomide alone and 16.6 +/- 2.87
h ug/ml with addition of regadenoson. The mean dialysate AUC was 2.9 +/- 1.2 h
ug/ml with temozolomide alone and 3.0 +/- 1.7 h ug/ml with regadenoson. The mean
brain:plasma AUC ratio was 18.0 +/- 7.8 and 19.1 +/- 10.7% for temozolomide alone
and with regadenoson respectively. Peak concentration and Tmax in brain were not
significantly different. CONCLUSIONS: Although previously shown to be efficacious
in rodents to increase varied size agents to cross the BBB, our data suggest that
regadenoson does not increase temozolomide concentrations in brain. Further
studies exploring alternative doses and schedules are needed; as transiently
disrupting the BBB to facilitate drug entry is of critical importance in neuro
oncology.
PMID- 29332605
TI - Antidepressant use during pregnancy and risk of autism spectrum disorder and
attention deficit hyperactivity disorder: systematic review of observational
studies and methodological considerations.
AB - BACKGROUND: Antidepressant exposure during pregnancy has been associated with an
increased risk of autism spectrum disorder (ASD) and attention deficit
hyperactivity disorder (ADHD) in several observational studies. We performed a
systematic review of these studies to highlight the effect that important
methodological limitations have on such analyses and to consider approaches to
the conduct, reporting and interpretation of future studies. METHODS: A review of
MEDLINE and EMBASE identified case-control, cohort and sibling studies assessing
the risk of ASD and ADHD with antidepressant use during pregnancy. Approaches to
confounding adjustment were described. Crude and adjusted effect estimates for
comparisons between antidepressant exposure during pregnancy vs. all unexposed
women were first meta-analysed using a generic inverse variance method of
analysis, followed by effect estimates for alternative pre-selected comparison
groups. RESULTS: A total of 15 studies measuring ASD as an outcome (involving
3,585,686 children and 40,585 cases) and seven studies measuring ADHD as an
outcome (involving 2,765,723 patients and 52,313 cases) were identified.
Variation in confounding adjustment existed between studies. Updated effect
estimates for the association between maternal antidepressant exposure during
pregnancy vs. all unexposed women remained statistically significant for ASD
(adjusted random-effects risk ratio [RaRR] 1.53, 95% confidence interval [CI]
1.31-1.78). Similar significant associations were observed using pre-pregnancy
maternal antidepressant exposure (RaRR 1.48, 95% CI 1.29-1.71) and paternal
antidepressant exposure during pregnancy (1.29, 95% CI 1.08-1.53), but analyses
restricted to using women with a history of affective disorder (1.18, 95% CI 0.91
1.52) and sibling studies (0.96, 95% CI 0.65-1.42) were not statistically
significant. Corresponding associations for risk of ADHD with exposure were: RaRR
1.38, 95% CI 1.13-1.69 (during pregnancy), RaRR 1.38, 95% CI 1.14-1.69 (during
pre-pregnancy), RaRR 1.71, 95% CI 1.31-2.23 (paternal exposure), RaRR 0.98, 95%
CI 0.77-1.24 (women with a history of affective disorder) and RaRR 0.88, 95% CI
0.70-1.11 (sibling studies). CONCLUSIONS: Existing observational studies
measuring the risk of ASD and ADHD with antidepressant exposure are heterogeneous
in their design. Classical comparisons between exposed and unexposed women during
pregnancy are at high risk of residual confounding. Alternative comparisons and
sibling designs may aid the interpretation of causality and their utility
requires further evaluation, including understanding potential limitations of
undertaking meta-analyses with such data.
PMID- 29332607
TI - The role of T2*-weighted gradient echo in the diagnosis of tumefactive
intrahepatic extramedullary hematopoiesis in myelodysplastic syndrome and diffuse
hepatic iron overload: a case report and review of the literature.
AB - BACKGROUND: Extramedullary hematopoiesis is the proliferation of hematopoietic
cells outside bone marrow secondary to marrow hematopoiesis failure.
Extramedullary hematopoiesis rarely presents as a mass-forming hepatic lesion; in
this case, imaging-based differentiation from primary and metastatic hepatic
neoplasms is difficult, often leading to biopsy for definitive diagnosis. We
report a case of tumefactive hepatic extramedullary hematopoiesis in the setting
of myelodysplastic syndrome with concurrent hepatic iron overload, and the role
of T2*-weighted gradient-echo magnetic resonance imaging in differentiating
extramedullary hematopoiesis from primary and metastatic hepatic lesions. To the
best of our knowledge, T2*-weighted gradient-echo evaluation of extramedullary
hematopoiesis in the setting of diffuse hepatic hemochromatosis has not been
previously described. CASE PRESENTATION: A 52-year-old white man with
myelodysplastic syndrome and marrow fibrosis was found to have a 4 cm hepatic
lesion on ultrasound during workup for bone marrow transplantation. Magnetic
resonance imaging revealed diffuse hepatic iron overload and non-visualization of
the lesion on T2* gradient-echo sequence suggesting the presence of iron
deposition within the lesion similar to that in background hepatic parenchyma.
Subsequent ultrasound-guided biopsy of the lesion revealed extramedullary
hematopoiesis. Six months later, while still being evaluated for bone marrow
transplant, our patient was found to have poor pulmonary function tests. Follow
up computed tomography angiogram showed a mass within his right main pulmonary
artery. Bronchoscopic biopsy of this mass once again revealed extramedullary
hematopoiesis. He received radiation therapy to his chest. However, 2 weeks
later, he developed mediastinal hematoma and died shortly afterward, secondary to
respiratory arrest. CONCLUSIONS: Mass-forming extramedullary hematopoiesis is
rare; however, our report emphasizes that it needs to be considered in the
initial differential diagnosis of hepatic lesions arising in the setting of bone
marrow disorders. We also show that in the setting of diffuse hepatic iron
overload, tumefactive extramedullary hematopoiesis appeared isointense to
background liver on T2* gradient-echo sequence, while adenoma, hepatoma, and
hepatic metastasis appear hyperintense. Thus, T2*-weighted gradient-echo sequence
may have a potential role in the imaging diagnosis of mass-forming hepatic
extramedullary hematopoiesis arising in the setting of diffuse iron overload.
PMID- 29332606
TI - Tricuspid flow and regurgitation in congenital heart disease and pulmonary
hypertension: comparison of 4D flow cardiovascular magnetic resonance and
echocardiography.
AB - BACKGROUND: Tricuspid valve (TV) regurgitation (TR) is a common complication of
pulmonary hypertension and right-sided congenital heart disease, associated with
increased morbidity and mortality. Estimation of TR severity by echocardiography
and conventional cardiovasvular magnetic resonance (CMR) is not well validated
and has high variability. 4D velocity-encoded (4D-flow) CMR was used to measure
tricuspid flow in patients with complex right ventricular (RV) geometry and
varying degrees of TR. The aims of the present study were: 1) to assess accuracy
of 4D-flow CMR across the TV by comparing 4D-flow CMR derived TV effective flow
to 2D-flow derived effective flow across the pulmonary valve (PV); 2) to assess
TV 4D-flow CMR reproducibility, and 3) to compare TR grade by 4D-flow CMR to TR
grade by echocardiography. METHODS: TR was assessed by both 4D-flow CMR and
echocardiography in 21 healthy subjects (41.2 +/- 10.5 yrs., female 7 (33%)) and
67 RV pressure-load patients (42.7 +/- 17.0 yrs., female 32 (48%)). The CMR
protocol included 4D-flow CMR measurement across the TV, 2D-flow measurement
across the PV and conventional planimetric measurements. TR grading on
echocardiographic images was performed based on the international
recommendations. Bland-Altman analysis and intra-class correlation coefficients
(ICC) were used to asses correlations and agreement. RESULTS: TV effective flow
measured by 4D-flow CMR showed good correlation and agreement with PV effective
flow measured by 2D-flow CMR with ICC = 0.899 (p < 0.001) and mean difference of
1.79 ml [limits of agreement -20.39 to 16.81] (p = 0.084). Intra-observer
agreement for effective flow (ICC = 0.981; mean difference - 1.51 ml [-12.88 to
9.86]) and regurgitant fraction (ICC = 0.910; mean difference 1.08% [-7.90;
10.06]) was good. Inter-observer agreement for effective flow (ICC = 0.935; mean
difference 2.12 ml [-15.24 to 19.48]) and regurgitant fraction (ICC = 0.968; mean
difference 1.10% [-7.96 to 5.76]) were comparable. In 25/65 (38.5%) TR grade
differed by at least 1 grade using 4D-flow CMR compared to echocardiography.
CONCLUSION: TV effective flow derived from 4D-flow CMR showed excellent
correlation to PV effective flow derived from 2D-flow CMR, and was reproducible
to measure TV flow and regurgitation. Twenty-five out of 65 patients (38.5%) were
classified differently by at least one TR grade using 4D-flow CMR compared to
echocardiography.
PMID- 29332608
TI - Concealed complete response in melanoma patients under therapy with immune
checkpoint inhibitors: two case reports.
AB - BACKGROUND: The assessment of tumor size by RECIST using CT scans and MRIs is
considered to be standard of care for staging cancer patients. Despite radiologic
evidence of widespread disease, we document for the first time that patients were
completely free of viable tumor. CASE PRESENTATION: Two patients with metastatic
melanoma were treated with immune checkpoint inhibitors (ipilimumab/ nivolumab)
and progressive metastases were detected on CT-scans performed shortly before
histologic examinations. In both patients histologic assessment revealed a
complete response with necrotic and scarred lesions free of tumor. One of the
patients had started immunotherapy 20 months before with an initial partial
response. CONCLUSIONS: This phenomenon of a concealed complete response can lead
to overtreatment or unnecessary change in treatment. Thus, it is essential to
raise awareness for it. Correct identification of responders to immune checkpoint
inhibitor therapy is crucial to spare patients immune-mediated side effects and
unnecessary as well as expensive treatment. Regression of metastases without
decline in size, in these cases manifesting as complete responses, are probably
more common than expected and identified to date. Until such responses can be
readily identified by new imaging techniques, we recommend liberal biopsies for
histologic assessment of progressive metastases in patients during and/or after
immune checkpoint inhibitor therapy.
PMID- 29332610
TI - Improvements in the conception rate, milk composition and embryo quality of
rabbit does after dietary enrichment with n-3 polyunsaturated fatty acids.
AB - This work attempts to confirm the effect of an enriched diet with n-3
polyunsaturated fatty acids (PUFA) trying to mitigate the reproductive
performances issues such as low conception rate of primiparous rabbits. A total
of 127 does were fed ad libitum throughout their two first cycles with two diets
with different fat sources: mixed fat in the control and salmon oil in the
enriched one, with 3.19 g/100 g (n=63 does) and 28.77 g/100 g (n=64 does) of n-3
of the total fatty acid, respectively. Feed intake was similar between groups
(P>0.05). Plasma progesterone concentration was higher in the enriched females
than in control ones at 7 (30.9+/-2.18 v. 23.9+/-2.30 ng/ml, respectively;
P=0.029) and 14 (38.7+/-2.18 v. 28.2+/-2.30 ng/ml, respectively; P=0.001) days of
first gestation. Considering both cycles, reproductive parameters of mothers
(fertility, duration of gestation and prolificacy) and litter parameters (weight
at parturition and weaning, mortality and average daily gain (ADG) of kits during
lactation) were similar in both groups. However, individual measurements of
neonates of enriched group improved 5.87%, 7.10% and 18.01% (P0.05), but embryo
apoptosis rate was higher in control group than in enriched one (31.1+/-4.56% v.
17.1+/-3.87%, respectively; P<0.05). In conclusion, dietary PUFA enrichment from
the rearing and throughout two productive cycles improved plasma progesterone
during pregnancy, fertility, milk fatty acid profile and neonates development of
primiparous supporting the beneficial effect of n-3 PUFA supplementation in
rabbit does.
PMID- 29332609
TI - Investigation of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and
mean platelet volume in patients with tinnitus.
AB - OBJECTIVE: This study aimed to evaluate patients with tinnitus in terms of mean
platelet volume and platelet distribution width, and to explore neutrophil-to
lymphocyte ratio and platelet-to-lymphocyte ratio, recently reported in the
literature as being possible inflammation markers. METHODS: This study comprised
64 tinnitus patients and 64 age-matched healthy controls. Statistical
significance level was accepted as p < 0.05. RESULTS: Mean platelet volume (t =
3.245, p = 0.002) and platelet distribution width (Z = 3.945, p < 0.001) were
significantly higher in the patient group than the control group. CONCLUSION: The
results suggest that a prothrombotic condition might play a role in the
pathophysiology of tinnitus.
PMID- 29332611
TI - Effect of rubber mats and perforation in the lying area on claw and limb lesions
of fattening pigs.
AB - Claw and leg lesions are frequently observed in finishing pigs and are likely to
compromise their welfare. Providing softer than the usual concrete flooring may
reduce both the frequency and severity of these lesions. Therefore, this study
evaluated the influence of rubber mats and floor perforation in the lying area on
claw and leg health of finishing pigs. A total of 240 Swiss Large White finishing
pigs from on average 24.9 kg until 102.3 kg were used in four batches, with six
groups of 10 animals per batch. The six experimental pens initially measured
1.85*3.55 m and were enlarged after 6 weeks to 1.85*5.25 m. In all pens, one
third of the floor space was built as a defecating area consisting of a concrete
floor with 15% perforation. The remaining two thirds of the pen were designed as
a lying area whose floor quality differed between the pens. It either consisted
of concrete elements or was covered with rubber mats, and perforation of both
floor types was either 0%, 5% or 10%. All individuals were scored for claw and
leg lesions at the beginning, in the middle and at the end of the 12-week
fattening period. Lesions were summarised in scores based on the results of a
principal component analysis. The influence on lesion scores of floor material,
amount of perforation in the lying area, assessment time, and sex was examined
using mixed-models. The total claw lesion score and the total limb lesion score
as well as the claw angle increased from the beginning to the end of the
fattening period. The values for both scores were slightly lower for animals kept
on rubber mats compared with animals kept on concrete floor. There was no effect
of the percentage of perforation on the examined outcome variables. In
conclusion, our results indicate that rubber mats in the lying area bring about
improvements in some aspects of claw and leg health in fattening pigs, whereas
there is no effect of floor perforation.
PMID- 29332612
TI - A Colonization Outbreak of Penicillin-Susceptible mecA-Positive Staphylococcus
aureus in a Neonatal Ward of Children's Hospital.
PMID- 29332613
TI - Should we tax unhealthy food and drink?
AB - The global burden of obesity leads to significant morbidity and has major
economic implications. In April 2018, Britain will join a growing number of
countries attempting to tackle this using fiscal measures when the UK Soft Drinks
Industry Levy is introduced. We review recent evidence from natural experiments
of the impact of health-related food and drink taxes on consumer behaviour, and
discuss the possible consequences of these approaches on purchases and health. We
highlight some of the potential indirect consequences and the importance of
robust prospective evaluation.
PMID- 29332614
TI - Serelaxin for infant heart failure in congenital dilated cardiomyopathy.
AB - Serelaxin has been studied in trials in adults with acute heart failure, but not
in children. We report the first compassionate use of serelaxin in an infant. A 6
month-old girl with dilated cardiomyopathy was placed on extracorporeal membrane
oxygenation following cardiac arrest unresponsive to medical treatment.
Extracorporeal membrane oxygenation weaning failed despite maximal ino-dilator
therapy. During the 48-hour infusion of serelaxin, we observed marked improvement
in brain natriuretic peptide, left ventricular systolic function, and dilatation.
The patient was successfully weaned from extracorporeal membrane oxygenation 24
hours later. The child died after a second extracorporeal membrane oxygenation
run owing to sepsis.
PMID- 29332615
TI - HIV EPIDEMIC HETEROGENEITY IN ZIMBABWE: EVIDENCE FROM SUCCESSIVE DEMOGRAPHIC AND
HEALTH SURVEYS.
AB - Zimbabwe has one of the worst HIV epidemics in the world. This study investigated
data from two successive Zimbabwe Demographic and Health Surveys (ZDHS) conducted
in 2005-06 and 2010-11. A random representative sample of 30,000 men aged 15-59
and women aged 15-49 was selected from the two surveys. The HIV prevalence was
mapped with a flexible, coherent regression framework using a geo-additive semi
parametric mixed model. HIV indicator prevalence maps were constructed at the
regional level, and at the administrative level relevant for policy design,
planning and decision-making. Substantial regional variation was found, not only
in the burden of HIV, but also in its risk factors. The results suggest that
responses/policies should vary at the regional level to ensure that the often
diverse needs of populations across a country are met and incorporated into
planning the HIV response. The use of geographically referenced data in two
successive ZDHS provides crucial new insights into the spatial characteristics of
the HIV epidemic in Zimbabwe. In particular, it highlights the HIV heterogeneity
across Zimbabwe, with substantial regional variation, not only in the burden of
HIV, but also in its risk factors.
PMID- 29332616
TI - Addressing Children's Needs in Disasters: A Regional Pediatric Tabletop Exercise.
AB - OBJECTIVE: Preparing and responding to the needs of children during public health
emergencies continues to be challenging. The purpose of this study was to assess
the usefulness of a tabletop exercise in initiating pediatric preparedness
strategies and assessing the impact of the exercise on participants'
understanding of and confidence in their roles during pediatric public health
emergencies. METHODS: A tabletop exercise was developed to simulate a public
health emergency scenario involving smallpox in a child, with subsequent spread
to multiple states. During the exercise, participants discussed and developed
communication, collaboration, and medical countermeasure strategies to enhance
pediatric public health preparedness. Exercise evaluation was designed to assess
participants' knowledge gained and level of confidence surrounding pediatric
public health emergencies. RESULTS: In total, 22 participants identified over 100
communication and collaboration strategies to promote pediatric public health
preparedness during the exercise and found that the most beneficial aspect during
the exercise was the partnership between pediatricians and public health
officials. Participants' knowledge and level of confidence surrounding a
pediatric public health emergency increased after the exercise. CONCLUSION: The
tabletop exercise was effective in identifying strategies to improve pediatric
public health preparedness as well as enhancing participants' knowledge and
confidence surrounding a potential pediatric public health emergency. (Disaster
Med Public Health Preparedness. 2018;12:582-586).
PMID- 29332617
TI - Decontamination of Extracorporeal Membrane Oxygenator Devices With an Intensified
Disinfection Protocol: How Strict Is Too Strict?
PMID- 29332618
TI - Online market research panel members as controls in case-control studies to
investigate gastrointestinal disease outbreaks: early experiences and lessons
learnt from the UK.
AB - Established methods of recruiting population controls for case-control studies to
investigate gastrointestinal disease outbreaks can be time consuming, resulting
in delays in identifying the source or vehicle of infection. After an initial
evaluation of using online market research panel members as controls in a case
control study to investigate a Salmonella outbreak in 2013, this method was
applied in four further studies in the UK between 2014 and 2016. We used data
from all five studies and interviews with members of each outbreak control team
and market research panel provider to review operational issues, evaluate risk of
bias in this approach and consider methods to reduce confounding and bias. The
investigators of each outbreak reported likely time and cost savings from using
market research controls. There were systematic differences between case and
control groups in some studies but no evidence that conclusions on the likely
source or vehicle of infection were incorrect. Potential selection biases
introduced by using this sampling frame and the low response rate are unclear.
Methods that might reduce confounding and some bias should be balanced with
concerns for overmatching. Further evaluation of this approach using comparisons
with traditional methods and population-based exposure survey data is
recommended.
PMID- 29332620
TI - CJEM Debate Series: #Copayment - Medical insurance is for non-routine events.
PMID- 29332621
TI - A New Chapter for CJEM.
PMID- 29332619
TI - Clinical characteristics of non-tuberculous mycobacterial pulmonary infections in
Bamako, Mali.
AB - The global spread of non-tuberculous mycobacteria (NTM) may be due to HIV/AIDS
and other environmental factors. The symptoms of NTM and tuberculosis (TB)
disease are indistinguishable, but their treatments are different. Lack of
research on the epidemiology of NTM infections has led to underestimation of its
prevalence within TB endemic countries. This study was designed to determine the
prevalence and clinical characteristics of pulmonary NTM in Bamako. A cross
sectional study which include 439 suspected cases of pulmonary TB. From 2006 to
2013 a total of 332 (76%) were confirmed to have sputum culture positive for
mycobacteria. The prevalence of NTM infection was 9.3% of our study population
and 12.3% of culture positive patients. The seroprevalence of HIV in NTM group
was 17.1%. Patients who weighed <55 kg and had TB symptoms other than cough were
also significantly more likely to have disease due to NTM as compared to those
with TB disease who were significantly more likely to have cough and weigh more
than 55 kg (OR 0.05 (CI 0.02-0.13) and OR 0.32 (CI 0.11-0.93) respectively). NTM
disease burden in Bamako was substantial and diagnostic algorithms for pulmonary
disease in TB endemic countries should consider the impact of NTM.
PMID- 29332623
TI - Gene expression and lymphocyte population at the fetal-maternal interface in
sheep pregnancies established by somatic cell nuclear transfer.
AB - The hypothesis of this study was that the leukocyte populations and expression
levels of genes related to immune response, growth factors and apoptosis would be
altered at the fetal-maternal interface in somatic cell nuclear transfer (SCNT)
generated sheep pregnancies. Placental and endometrial samples from sheep
pregnancies established by SCNT and natural breeding (control) were collected at
45 days and at term. Expression of genes related to growth factors, apoptosis and
immune response was examined using quantitative reverse transcription polymerase
chain reaction. Endometrial leukocyte populations and major histocompatibility
class I (MHC-I) protein expression were examined by immunohistochemistry. At term
we observed altered expression of genes related to apoptosis, growth factors and
immune response in placental and endometrial tissue of SCNT pregnancies. In Day
45 pregnancies there was less-pronounced abnormal expression and only genes
related to apoptosis and growth factors were abnormal in the placenta.
Endometrial gene expression profiles were similar to age-matched controls.
Placental MHC-I protein expression was similar in SCNT and controls at 45 days
but increased in the SCNT at term. The altered gene expression at the fetal
maternal interface likely contributes to the placental dysfunction and overgrowth
observed in sheep SCNT pregnancies.
PMID- 29332622
TI - In vivo and in vitro strategies to support caprine preantral follicle development
after ovarian tissue vitrification.
AB - The aim of the present study was to compare fresh and vitrified goat ovarian
tissue after autotransplantation and in vitro culture. Adult goats were
completely ovariectomised and each ovarian pair was sliced and distributed among
six different treatment groups: fresh control, fresh transplant, fresh culture,
vitrified control, vitrified transplant and vitrified culture. Follicular
morphology, development, growth, density, revascularisation and hormone
production were evaluated in all groups. Three antral follicles (two in the fresh
transplant and one in the vitrified transplant groups) were observed on the
surface of the graft 90 days after transplantation. The percentage of
morphologically normal follicles was similar in the fresh control, fresh
transplant and vitrified transplant groups. The percentage of developing
(transition, primary and secondary) follicles was higher after in vitro culture
of fresh or vitrified tissue. Transplantation resulted in a lower follicle
density. Serum oestradiol concentrations remained constant during the entire
transplantation period. In contrast, progesterone production decreased
significantly. Expression of CD31 mRNA was lower in fresh culture. In conclusion,
restoration of goat ovarian function can be successfully achieved following
transplantation of both fresh and vitrified goat ovarian tissue. However,
transplantation induced higher follicle loss than in vitro culture.
PMID- 29332624
TI - [Not all exacerbations of chronic obstructive pulmonary disease should be treated
with antibiotics].
AB - This review gives an update on antibiotic treatment of exacerbation of chronic
obstructive pulmonary disease (COPD). Patients who do not need hospital admission
and do not present with purulent sputum nor increased levels of C reactive
protein/procalcitonin have no beneficial effect of antibiotic treatment. Those
with severe COPD and increased sputum purulence should be treated with
antibiotics, and first-line treatment should be amoxicillin, which is effective
against the most common types of bacteria in COPD exacerbation. In patients with
very severe COPD, amoxicillin/clavulanate could also be first-line treatment.
PMID- 29332625
TI - Positive and negative affect mediate the bidirectional relationship between
emotional processing and symptom severity and impact in irritable bowel syndrome.
AB - INTRODUCTION: Individuals with IBS report higher levels of psychological distress
compared to healthy controls. Distress has been associated with emotional
processing difficulties but studies have not explored how the relationship
between distress and emotional processing affects IBS. There is little research
on the role of positive affect (PA) in IBS. AIMS: (a) If difficulties in self
reported emotional processing are associated with affect and IBS measures (i.e.,
symptom severity, interference in life roles) (b1) If affect mediates the
relationship between emotional processing and IBS measures (b2) Alternative
model: if affect mediates the relationship between IBS and emotional processing
(c) If PA moderates the relationship between distress and IBS. METHODS:
Participants with a confirmed diagnosis of IBS (n=558) completed a questionnaire
including measures of emotional processing (i.e., unhelpful beliefs about
negative emotions, impoverished emotional experience), distress, PA, and IBS
symptoms/interference. Mediation and moderation analyses were conducted with
Maximum Likelihood Estimation. RESULTS: Distress and PA mediated or partly
mediated the relationship between unhelpful beliefs about negative
emotions/impoverished emotional experience and both IBS measures. The alternative
models were also valid, suggesting a two-way relationship between emotional
processing and IBS through affect. PA did not moderate the relationship between
distress and IBS. CONCLUSION: Future interventions in IBS may benefit from not
only targeting the management of physical symptoms and their daily impact but
also aspects related to the experience of both negative and positive affect, and
the acceptance and expression of negative emotions. Longitudinal studies are
needed to confirm causal relationships within the explored models.
PMID- 29332626
TI - Symptoms of depression and anxiety and 11-year all-cause mortality in men and
women undergoing coronary artery bypass graft (CABG) surgery.
AB - OBJECTIVES: To investigate the overall and the sex-specific association of
preoperative and one-year post coronary artery bypass (CABG) surgery symptoms of
depression and anxiety with 11-year all-cause mortality. METHODS: A multicenter
prospective study including 1125 patients who completed the Hospital Anxiety and
Depression Scale (HADS) before an elective CABG surgery, of whom 850 completed
the HADS again at one-year follow-up. Information on all-cause mortality was
obtained through the Israeli Ministry of Internal Affairs Register. Multivariable
adjusted Cox regression models quantified the association of symptoms of
depression and anxiety with all-cause mortality. RESULTS: Females comprised 22.7%
of the cohort and were 5.5years older than males (70.0+/-9.3 and 64.4+/
10.3years, respectively). Controlling for sociodemographic and lifestyle factors,
illness severity and post-surgery participation in cardiac rehabilitation, there
was little evidence of an association between preoperative symptoms of depression
and mortality in males [adjusted hazard ratio (aHRmales)=1.03, 95% CI 0.99-1.07,
p=0.21] or females (aHRfemales=1.01, 95% CI 0.95-1.08, p=0.7). One-year
postoperative symptoms of depression were associated with mortality in both males
(aHRmales=1.05, 95% CI 1.01-1.10, p=0.03) and females (aHRfemales=1.07, 95% CI
1.02-1.13, p=0.013). Preoperative symptoms of anxiety were unrelated to mortality
overall, but among females postoperative symptoms of anxiety predicted 11-year
mortality (aHRfemales=1.07, 95% CI 1.00-1.14, p=0.049). There was no HADS by sex
interaction (p for interaction=0.12-0.99). CONCLUSIONS: Symptoms of depression
one-year after surgery were positively related to mortality with little evidence
for sex differences. These findings underscore the need for identification and
treatment of psychiatric symptoms in patients undergoing CABG surgery. CLINICAL
TRIAL REGISTRATION: ClinicalTrials.gov: NCT00356863.
PMID- 29332627
TI - Pre-transplant history of mental health concerns, non-adherence, and post
transplant outcomes in kidney transplant recipients.
AB - OBJECTIVE: The association between pre-transplant mental health concerns and non
adherence and post-transplant outcomes after kidney transplantation is not fully
established. We examined the relationship between a pre-transplant history of
mental health concerns and non-adherence and post-transplant outcomes among
kidney transplant recipients. METHODS: In this retrospective single center cohort
study of adult kidney transplant recipients (n=955) the associations between the
history of mental health concerns or non-adherence and the time from kidney
transplant to biopsy proven acute rejection; death-censored graft failure and
total graft failure were examined using Cox proportional hazards models. RESULTS:
Mean (SD) age was 51 (13) years, 61% were male and 27% had a history of diabetes.
Twenty-two and 11% of patients had mental health concerns and non-adherence,
respectively. Fifteen percent of the patients had acute rejection, 5.6% had death
censored graft failure and 13.0% had total graft failure. The history of mental
health concerns was not associated with acute rejection, death-censored graft
failure or total graft failure. Patients with versus without a history of non
adherence tended to have higher cumulative incidence of acute rejection (23.3%
[95% CI: 16.1, 33.2] vs. 13.6% [95% CI: 11.4, 16.2]) and death-censored graft
failure (15.0% [95% CI: 6.9, 30.8] vs. 6.4% [95% CI: 4.7, 8.7]) (log rank p=0.052
and p=0.086, respectively). These trends were not significant after multivariable
adjustment. CONCLUSION: In summary, a history of pre-transplant mental health
concerns or non-adherence is not associated with adverse outcomes in patients who
completed transplant workup and received a kidney transplant.
PMID- 29332628
TI - Socioeconomic factors in coronary artery disease - Results from the SPIRR-CAD
study.
AB - : Low socio-economic status (SES) has been associated with an increased coronary
risk in Western countries. All stress experiences are more pronounced in low SES
patients with stress emanating from problems with family, job, or money. The
SPIRR-CAD study offered an excellent opportunity to examine these risk factors in
German speaking mildly and medium depressed patients. In the SPIRR CAD study, a
German multi centre randomized clinical trial of 450 male and 120 female coronary
patients, we examined the standard and psychosocial risk factor profiles in
relation to SES, as assessed by educational level. All differences in risk
factors between low and high SES were in the inverse direction. Of standard risk
factors, only smoking was socially graded and more common in low SES. Of
psychosocial factors and emotions, exhaustion showed the strongest and most
consistent inverse social gradient, but also anger, anxiety and depression were
socially graded. The findings suggest that in German patients, as in other
national groups, social gradients in CHD risk are considerable. They can be
ascribed to both psychosocial and to standard risk factors. In the present two
years follow-up, the prospective significance of psychological and social risk
factors was analyzed showing that emotional factors played an important role, in
that low and high SES patients differed in the expected direction. However, the
differences were not statistically significant and therefore firm conclusions
from follow up were not possible. TRIAL REGISTRATION: ISRCTN 76240576;
NCT00705965.
PMID- 29332629
TI - Psychobiological stress in vital exhaustion. Findings from the Men Stress 40+
study.
AB - OBJECTIVE: Despite the increased risk for cardiovascular morbidity associated
with vital exhaustion (VE), the underlying pathophysiological mechanisms remain
unclear. Allostatic load may constitute the missing link between VE and
cardiovascular diseases. The aim of the present study was to investigate whether
men with different degrees of VE would differ in terms of allostatic load,
chronic stress, and social support. METHODS: The Men Stress 40+ study sample
consisted of N=121 apparently healthy men aged 40 to 75years. The following
allostatic load markers were aggregated to create a cumulative index of
biological stress: salivary cortisol, salivary dehydroepiandrosterone sulfate
(DHEA-S), waist-to-hip-ratio, systolic and diastolic blood pressure. Long-term
cortisol and DHEA were additionally measured in hair. Chronic stress and social
support were assessed via validated questionnaires. Groups of mildly,
substantially, and severely exhausted men were compared using one-way ANOVAs with
appropriate post-hoc tests. RESULTS: Men who reported mild or severe levels of
vital exhaustion had the highest scores on the cumulative index of biological
stress. Hair cortisol was unrelated to vital exhaustion; hair DHEA was highest in
men with substantial levels of exhaustion. Men with mild exhaustion reported the
lowest levels of chronic stress, while men with severe exhaustion reported the
lowest levels of social support. CONCLUSIONS: Signs of allostatic load are
detectable in vitally exhausted men at a stage where no major cardiovascular
consequences have yet ensued.
PMID- 29332630
TI - Effects of a program of cognitive-behavioural group therapy, vestibular
rehabilitation, and psychoeducational explanations on patients with dizziness and
no quantified balance deficit, compared to patients with dizziness and a
quantified balance deficit.
AB - BACKGROUND: We examined whether a program combining cognitive-behavioural therapy
(CBT), vestibular rehabilitation (VR) and psychoeducation is equally effective in
improving psychometric measures in patients with dizziness independent of a
balance deficit. Measures of patients with dizziness only (DO) were compared to
those of patients also having a quantified balance deficit (QBD). METHODS: 32
patients (23 female, 9 male) with persistent dizziness were analysed as 2 groups
based on stance and gait balance control: those with QBD (pathological balance)
or DO (normal balance). Dizziness Handicap Inventory (DHI) and Brief Symptom
Inventory (BSI) questionnaires were used pre- and post-therapy to assess
psychometric measures. Patients then received the same combination therapy in a
group setting. RESULTS: The QBD group mean age was 60.6, SD 8.3, and DO group
mean age 44.8, SD 12.1, years. Pre-therapy, questionnaire scores were
pathological but not different between groups. Balance improved significantly for
the QBD group (p=0.003) but not for the DO group. DHI and BSI scores improved
significantly in the DO group (0.001=2.47), but not in
Europe (aOR=1.26, 95%CI=0.90-1.77). Analyses with self-reports of diagnosed
asthma yielded similar, albeit weaker, associations (e.g. OR for the overall
sample=1.63, 95%CI=1.38-1.92). We also combined asthma and wheezing into a single
variable (reference group: no asthma diagnosis/no wheezing). We observed that in
particular reports of wheezing were associated with impaired social functioning
regardless of whether a concomitant asthma diagnosis was reported (OR=2.19,
95%CI=1.81-2.64) or not (OR=2.50, 95%CI=2.09-2.99). CONCLUSION: Self-reports of
wheezing and of diagnosed asthma are associated with impaired social functioning
among adults in Africa, South America and Asia, but less so in Europe. These
relationships are mainly driven by the experience of respiratory symptoms (i.e.
wheezing). Our findings may partly be explained by regional variations in asthma
control. Further research should elucidate the determinants and mechanisms of
asthma-related impaired social functioning.
PMID- 29332635
TI - Fear of hypoglycemia in patients with type 2 diabetes: The role of interoceptive
accuracy and prior episodes of hypoglycemia.
AB - OBJECTIVE: Fear of hypoglycemia (FoH) is a limiting factor for diabetes self
management and can have detrimental effects on quality of life. However,
relatively little is known about its underlying mechanisms. In line with findings
on patients with anxiety disorders, we hypothesized that interoceptive accuracy
(IA) might be positively linked to FoH in patients with type 2 diabetes (T2DM).
METHODS: 133 patients with T2DM were screened according to the extreme quartiles
of the Hypoglycemia Fear Survey worry subscale (HFS-W). Overall, 66 participants
(HFS-W<4; HFS-W>17) were included in the present study. Participants completed
questionnaires on sociodemographic and diabetes-related measures. Accuracy of
heartbeat perception was assessed using the mental tracking task. RESULTS:
Contrary to expectations, IA did not differ significantly between patients with
low and high FoH. A linear regression analysis demonstrated that the experience
of mild hypoglycemia (beta=0.32, p<=0.01) and its interaction with IA (beta=
0.26, p=0.040) were significant predictors of FoH, indicating that low IA and a
history of experiencing mild hypoglycemia are positively associated with FoH.
CONCLUSION: Our findings suggest a positive association of low IA in combination
with prior episodes of hypoglycemia and FoH in patients with T2DM. The results
are in line with recent findings on IA in patients with chronic somatic symptom
distress more generally and contribute to our understanding of the relations
between interoception, body related fears, and physical symptom perception.
PMID- 29332636
TI - Implementation of an electronic routine outcome monitoring at an inpatient unit
for psychosomatic medicine.
AB - BACKGROUND: Patient-reported outcomes (PROs) can be part of an electronic routine
outcome monitoring (eROM). eROM can improve patient involvement, treatment
outcomes and simplify scientific data assessment. Available studies on eROM focus
on its evaluation only and lack a detailed description of the prior
implementation procedure. OBJECTIVE: The aim was to implement an eROM assessment
at a division of Psychosomatic Medicine and provide a detailed description of the
implementation procedure. METHODS: According to the Replicating Effective Program
concept the project consisted of 4 phases: pre-condition (1), pre-implementation
(2), implementation (3) and maintenance and evolution (4) mainly focusing the
description of the implementation procedure and a short evaluation. RESULTS: We
describe the actions taken during the implementation procedure and steps which
were taken to overcome identified barriers. All decisions were carried out based
on the Participatory Action Research process. A core set consisting of
sociodemographic and clinical data and a comprehensive questionnaire battery
covering symptoms, functioning parameters and psychological constructs was
implemented. In total 164 patients, took part in the eROM assessment from June
2015 to December 2016. The evaluation showed that eROM was appreciated by health
care professionals (85.2%) and patients (70.2%) alike. The majority of patients
(89.4%) and health-care professionals (85.7%) experienced no delays in daily
clinical routine due to eROM. CONCLUSION: The detailed description of the
implementation process can guide institutions planning to implement eROM into
their daily clinical routine. Focusing scientific efforts on the implementation
process is essential since this influences all further steps such as evaluation
and acceptance.
PMID- 29332637
TI - Pilot-RCT of an integrative group therapy for patients with refractory irritable
bowel syndrome (ISRCTN02977330).
AB - OBJECTIVE: Different forms of psychotherapeutic treatments have been proven
effective in irritable bowel syndrome (IBS), but disorder-oriented and
integrative concepts are still rare. Therefore, we implemented and evaluated an
integrative group therapeutic concept within an interdisciplinary tertiary care
clinic for functional gastrointestinal disorders (FGIDs). AIMS: present our
integrative group concept, assess feasibility issues, and evaluate efficacy.
METHODS: A pilot-RCT with a randomized controlled wait-listed group design was
conducted. The treatment concept was a disorder-oriented multicomponent group
therapy (12 90-min weekly sessions) integrating interactive psychoeducation, gut
directed hypnotherapy, and open group phases. All patients received enhanced
medical care and completed a short online diary as an active wait-listed control
condition. INCLUSION CRITERIA: refractory IBS diagnosed as somatoform autonomic
dysfunction of the lower gastrointestinal tract (SAD). PRIMARY OUTCOME: IBS
symptom severity (IBS-SSS). RESULTS: Of 294 patients, 220 had IBS (ROME III), 144
were diagnosed as SAD (ICD-10), 51 were eligible regarding inclusion/exclusion
criteria, and 30 consented to participate (group intervention: n=16, wait-listed
control condition: n=14). Only 1 patient dropped out. Intention-to-treat-analysis
with repeated-measures mixed ANOVA showed that the group intervention was not
significantly superior to the wait-listed control condition. Nevertheless, the
calculated effect size for the between-group difference in IBS-SSS at the end of
treatment (post) was moderate (d=0.539). CONCLUSION: Our disorder-oriented
integrative group intervention for IBS proved to be acceptable and feasible in an
interdisciplinary tertiary care setting. There is promise in this intervention,
but a larger RCT may be needed to investigate efficacy.
PMID- 29332638
TI - The effect of exercise therapy on depressive and anxious symptoms in patients
with ischemic heart disease: A systematic review.
AB - OBJECTIVE: Depressive and anxiety symptoms are associated with Ischemic Heart
Disease (IHD). Exercise interventions might improve both depressive and anxiety
symptoms, but an overview of the evidence is lacking. Therefore, we
systematically reviewed the existing literature on the effectiveness of exercise
therapy to reduce depression and anxiety symptoms specifically in patients with
IHD. METHODS: MEDLINE, EMBASE, PsycINFO and the Cochrane Central Register of
Controlled Trials were searched until January 2016. The effectiveness of exercise
was assessed within two groups: a) patients selected for study with severe
depression or anxiety; and b) studies that did not exclusively targeted patients
with increased levels of depression or anxiety. Secondary outcomes were
mortality, cardiac events, re-hospitalizations and cardiovascular risk factors.
RESULTS: We included fourteen studies. Clinical and methodological heterogeneity
precluded meta-analysis. Three studies specifically included patients with high
levels of depression or anxiety and eleven studies selected patients with unclear
levels of depression or anxiety. Some RCTs showed that exercise was effective in
lowering severe depressive symptoms (short and long term follow-up), but for the
group with unclear depressive symptoms the results were non-conclusive. In the
group with elevated anxiety symptoms, exercise had a positive effect on the short
term follow-up. In the group with unclear anxiety symptoms the results were
inconsistent (short and long term follow-up). No differences were found regarding
the secondary outcomes. CONCLUSIONS: There is a general paucity of data on the
effect of exercise, precluding firm conclusions about the effectiveness of
exercise for depressive and anxiety symptoms in IHD patients.
PMID- 29332639
TI - Genetic and environmental influences to low back pain and symptoms of depression
and anxiety: A population-based twin study.
AB - BACKGROUND: People suffering from chronic pain are more likely to experience
symptoms of depression and anxiety. However, the mechanisms underlying this
relationship remain largely unknown. In light of the moderate to large effects of
genetic factors on chronic pain and depression and anxiety, we aimed to estimate
the relative contribution of genetic and environmental factors to the
relationship between these traits. METHODS: Using data from 2139 participants in
the Murcia Twin Registry, we employed a bivariate analysis and structural
equation modeling to estimate the relative influences of genetics and the
environment on the covariation between low back pain and symptoms of depression
and anxiety. RESULTS: We have obtained heritability estimates of 0.26 (95%
Confidence Interval (CI) 0.11, 0.41) for chronic low back pain and 0.45 (95% CI
0.29, 0.50) for symptoms of depression and anxiety. The phenotypic, genetic, and
unique environment correlations in the bivariate analytical model were,
respectively, rph=0.26 (95% CI 0.19, 0.33); rG=0.47 (95% CI 0.42, 0.70); rE=0.14
(95% CI -0.04, 0.25). The percentage of covariance between low back pain and
symptoms of depression and anxiety attributable to additive genetic factors was
63.6%, and to unique environment 36.4%. CONCLUSIONS: Our findings confirm the
relationship between low back pain and symptoms of depression and anxiety in a
non-clinical sample. Shared genetic factors affect significantly the covariation
between these conditions, supporting the role of common biological and
physiological pathways.
PMID- 29332640
TI - Cognitive impairment in patients with psoriasis: A matched case-control study.
AB - BACKGROUND: In the past decade, a few studies have suggested that psoriasis could
be associated with the presence of mild cognitive deficits. OBJECTIVES: The aim
of the present matched case-control study was to investigate several cognitive
domains (executive functions, verbal memory, attention, and language) in a sample
of outpatients with psoriasis. We also investigated whether cognitive impairment
was associated with poor health-related quality of life (HRQoL) in patients with
psoriasis. METHODS: Fifty adult outpatients and 50 age- and sex-matched healthy
controls were administered a battery of neuropsychological tests investigating
major cognitive domains, psychopathology (anxiety and depression), alexithymia,
and HRQoL. RESULTS: At the bivariate level, psoriasis patients (compared to
healthy controls) performed worse on most of the neuropsychological tests, and
they also reported more anxiety and depressive symptoms, higher scores for
alexithymia, and worse physical and mental health. At the multivariate level,
cognitive performance was independently associated with psoriasis even when
controlling for psychopathology and alexithymia. CONCLUSIONS: Patients with
psoriasis show impaired cognitive performance, high levels of anxiety and
depression, and impaired quality of life. Based on the current results,
clinicians should assess the presence of psychological symptoms in their patients
and evaluate whether the presence of cognitive deficits is limiting the patients'
ability to cope with the disease.
PMID- 29332641
TI - Epidemiological paradigm: Tuberculosis in HIV, diabetes, and smoking in North
East India: An impact greater than sum of its parts.
PMID- 29332642
TI - Current Affairs, Future Perspectives of Tuberculosis and Antitubercular Agents.
AB - Tuberculosis (TB) is the major threat for humans from past several decades. Even
after advent of several antitubercular drugs, researchers are still struggling
for the mycobacterial infections in humans are TB and leprosy. Chronic infections
caused by Mycobacterium tuberculosis and Mycobacterium leprae. A particular
problem with both of these organisms is that they can survive inside macrophages
after phagocytosis, unless these cells are activated by cytokines produced by T
lymphocytes, because of this researchers are not yet succeeded in finding
effective treatment on TB. In recent years TB has spread globally and became the
major issue for world healthcare organizations. Some compounds like
benzothiazinones shown promising activity against mycobacterium, few compounds
are in pipeline which may exhibit improved pharmacological effect.
Decaprenylphosphoryl-d-ribose 2'-epimerase (DprE1) is the vulnerable target for
antitubercular drug discovery. DprE1 is a flavoprotein that along with
decaprenylphosphoryl-2-keto-ribose reductase catalyses epimerization of
decaprenylphosphoryl-d-ribose to decaprenylphosphoryl-d-arabinose through an
intermediate formation of decaprenylphosphoryl-2-keto-ribose. This conversion
makes DprE1 a potential drug target. Further research requires to tackle the
biggest hurdles in Tuberculosis treatment, i.e. multi drug and extensively drug
resistance.
PMID- 29332643
TI - Role of laparoscopy in diagnosing genital tuberculosis in suspected women: A
cross-sectional study from a tertiary care hospital in Northern India.
AB - This study was included 60 women with suspected genital tuberculosis, attending
outpatient department of a tertiary care hospital. The aim was to evaluate the
role and accuracy of laparoscopy in the diagnosis of genital tuberculosis. The
patients were investigated for tuberculosis with Erythrocyte Sedimentation Rate,
Montoux, chest X-ray, serum ELISA, CA125, ultrasonography, endometrial biopsy and
laparoscopic biopsy. Culture or histopathology was taken as a gold standard for
confirming the cases of genital tuberculosis. 30 patients were confirmed as
positive. Comparison was made between the various diagnostic modalities. Baseline
investigations like complete blood count, differential leukocyte count, ESR,
Montoux, and some special tests like CA125 and serum ELISA were helpful in
supporting the diagnosis in only some patients. The sensitivity, specificity,
positive and negative predictive value of endometrial biopsy in diagnosing GT was
6.6%, 100%, 100% and 51.7% respectively. Laparoscopic gross visualization alone,
staining, culture and histology were able to detect 86.6%, 33.3%, 50% and 63.3%
of cases respectively. Many patients would have been missed if laparoscopy was
not performed. It helps in macroscopic visualization of pelvic cavity and
obtaining biopsies for ZN staining, culture and histopathology. This increases
the pickup rate of positive cases and helps in confirmation of the diagnosis.
PMID- 29332645
TI - Plasma levels of Rifampicin and Pyrazinamide with pre and post meal
administration in tuberculosis patients.
AB - CONTEXT: Various factors affect plasma concentrations of antitubercular drugs in
different populations so dosing schedule should be adjusted after therapeutic
drug monitoring. AIMS: To study variability in plasma concentrations of
Rifampicin and Pyrazinamide with pre and post-meal administration of drugs in
tuberculosis patients. METHODS AND MATERIAL: 52 patients of pulmonary
tuberculosis, divided in to two groups, pre and post-meal through systemic
randomization. After taking pre-dose sample, drugs were administered according to
the group. Samples were withdrawn at 2, 4, 6, and 10h after drug administration.
Analysis of samples was done using HPLC. RESULTS: Mean+/-1SD of Cmax of
Rifampicin was 7.75+/-2.82MUg/ml, mean+/-1SD of AUC0-10 was 42.17+/-17.25MUgh/ml,
adjusted Tmax was 4.25h. In pre-meal samples, the corresponding values were
7.75+/-2.88MUg/ml, 42.83+/-18.47MUgh/ml, 3.76h and in post-meal samples 8.03+/
2.30MUg/ml, 41.56+/-16.46MUgh/ml and 4.75h. Mean+/-1SD of Cmax levels of
Pyrazinamide was 54.49+/-21.86MUg/ml, mean+/-1SD of AUC0-10 was 337.94+/
124.28MUgh/ml and adjusted Tmax was 3.49h. In pre-meal samples the corresponding
values were 52.00+/-19.13MUg/ml, 329.96+/-112.11MUgh/ml, 3.23h, and in post-meal
samples 57.43+/-23.61MUg/ml, 345.58+/-136.99MUgh/ml, 3.54h. CONCLUSION: There is
huge variability in the plasma levels of Rifampicin and Pyrazinamide in
population of this sub-himalayan region.
PMID- 29332644
TI - Role of serum adenosine deaminase in pulmonary tuberculosis.
AB - BACKGROUND: Definitive laboratory diagnosis and confirmation of tuberculosis
remains a major challenge because of lack of specificity and sensitivity of
diagnostic methods especially in sputum smear negative tuberculosis. Many studies
have proved the role of ADA in diagnosis of tuberculosis in effusion fluids and a
decrease in ADA activity after treatment. This study was aimed to investigate the
role of serum ADA level as an early diagnostic and prognostic marker for
pulmonary tuberculosis (PTB). MATERIAL AND METHODS: This was a cohort study done
on patients visiting the OPD Clinics of the department of Pulmonary Medicine at
GMCH, Chandigarh. 50 sputum positive and 50 sputum negative tuberculosis patients
and 100 controls were recruited. Serum ADA levels were measured at the start of
treatment and again after two months of treatment. Its correlation with severity
of disease was seen. RESULTS: Mean serum ADA (IU/L) was found to be 35.293+/
30.941 in PTB patients and 11.819+/-8.023 in control groups and the difference
was found to be highly significant (P<0.00). Mean ADA was 31.107+/-29.32 in
sputum positive patients, 39.478+/-32.22 in sputum negative and 11.819+/-8.0235
in control groups. No statistically significant difference was observed amongst
sputum positive and sputum negative patients. The levels decreased significantly
after intensive phase of treatment. At the cut off values of 14.6IU/L, serum ADA
had 78% sensitivity and 76% specificity (AUC=0.801, P value<0.00) to
differentiate between PTB from healthy controls. CONCLUSION: Serum ADA levels may
be used as a biomarker for diagnosis of PTB and to evaluate the response to
treatment at follow up.
PMID- 29332646
TI - Strategy and way forward for TB elimination.
AB - India's National Strategic Plan (NSP) for TB Elimination 2017-25 looks ambitious
in terms of targets of TB notification aiming to reach 35 lakh TB patients
annually, i.e. double that of current status. Strategies and interventions
designed under the Plan with patient centered approaches, with synergistic public
private-patient partnership can make it possible to achieve real aim of reaching
the unreached, by extending patient support systems and social protection to
affected communities. In this review point, these strategies and commitments are
summarized as future plan.
PMID- 29332647
TI - Social support a key factor for adherence to multidrug-resistant tuberculosis
treatment.
AB - BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is emerging as a major
public health problem globally. Treatment success rates in MDR-TB across the
globe are not encouraging as completing MDR-TB treatment successfully is
challenging due to high proportion of lost to follow up. METHODS: Using
qualitative methods and grounded theory approach, in-depth interviews were
conducted with MDR-TB patients and treatment providers. The social cognitive
framework was explored as a way to guide understanding of the factors affecting
treatment adherence among MDR-TB patients. RESULTS: Multiple factors influenced
patient's decision to adhere to MDR-TB treatment. Self-motivation, awareness
about disease and treatment, counselling support, family support, nutritional
support and social support were important drivers for successful treatment.
Providers related that motivational counselling, nutritional support, family
support and social support encouraged treatment adherence. CONCLUSION: To improve
MDR-TB treatment adherence, a patient-centric approach should be considered at
the programmatic level. There is a need to formulate strategy that includes
motivational counselling, nutritional supplementation and social support
mobilisation for treatment adherence. Participants suggested a Patient Support
Group led treatment care model for better adherence and treatment success rates
in MDR-TB treatment.
PMID- 29332648
TI - Prevalence of chronic respiratory diseases from a rural area in Kerala, southern
India.
AB - BACKGROUND: Chronic lung diseases are one of the leading causes of morbidity in
developing countries. A community based survey was undertaken with an objective
to estimate the prevalence of chronic respiratory diseases and to describe the
profile of people with CRDs in the rural area Nilamel health block in Kollam
district, Kerala, southern India. METHODS: A household information sheet and a
translated respiratory symptom questionnaire based on International Union against
Tuberculosis and Lung Disease (IUATLD) bronchial symptoms questionnaire was
administered to 12,556 people above 15 years, selected randomly from Nilamel
health block. RESULTS: Prevalence of self reported asthma was 2.82% (95% CI 2.52
3.12) and that of chronic bronchitis was 6.19% (95% CI 5.76-6.62) while other
CRDs which did not fit to either constitute 1.89%. Prevalence of asthma among
males was 2.44% (95% CI 2.05-2.85) while that of females was 3.14% (95% CI 2.71
3.57). Chronic bronchitis prevalence was 6.73% and 5.67% among males and females
respectively. CONCLUSION: Although India has devised a programme to combat
cancer, diabetes, cardio vascular disease and stroke, none have been devised for
chronic respiratory illness till date. Considering high prevalence and its
contributions to morbidity and mortality, a comprehensive programme to tackle
chronic respiratory diseases is needed.
PMID- 29332649
TI - Isoniazid and rifampicin heteroresistant Mycobacterium tuberculosis isolated from
tuberculous meningitis patients in India.
AB - BACKGROUND: Heteroresistant Mycobacterium tuberculosis (mixture of susceptible
and resistant subpopulations) is thought to be a preliminary stage to full
resistance and timely detection, initiation of correct treatment is vital for
successful anti tubercular therapy. The aim of this study was to detect multi
drug resistant (MDR) and heteroresistant M. tuberculosis with the associated gene
mutations from patients of tuberculous meningitis. METHODS: A total of 197 M.
tuberculosis isolates from 478 patients of TBM were isolated from July 2012 to
July 2015 and subjected to drug susceptibility testing (DST) by BACTEC MGIT and
Genotype MTBDR line probe assay (LPA). Heteroresistance was defined as presence
of both WT and mutant genes in LPA. RESULTS: Of 197 M. tuberculosis isolates, 11
(5.6%) were MDR, 23 (11.6%), 1 (0.5%) were mono resistant to isoniazid (INH) and
rifampicin (RMP) respectively. Heteroresistance was detected in 8 (4%), 2 (1%)
isolates to INH and RMP respectively. INH heteroresistant strains had WT bands
with mutation band S315T1 whereas RMP heteroresistant strains had WT bands with
mutation band S531L. CONCLUSION: The prevalence of MDR M. tuberculosis was 5.6%
in TBM patients with the most common mutation being DeltaWT band with S315T1 for
INH and DeltaWT band with S531T for RMP. MGIT DST was found to be more sensitive
for detecting overall resistance in M. tuberculosis but inclusion of LPA not only
reduced time for early initiation of appropriate treatment but also enabled
detection of heteroresistance in 8 (4%), 2 (1%) isolates for INH and RMP
respectively.
PMID- 29332650
TI - Amplification of Hsp 65 gene and usage of restriction endonuclease for
identification of non tuberculous rapid grower mycobacterium.
AB - BACKGROUND: The rapid grower mycobacteria have emerged as significant group of
human pathogen amongst the Runyon group IV organisms that are capable of causing
infection in both the healthy and immunocompromised hosts. Study aimed to
identification of species amongst rapid grower non tuberculous mycobacterial
isolates by polymerase chain reaction - restriction enzyme analysis (PRA).
Analysis and comparison of results with standard biochemical tests. METHODS:
Rapid grower non tuberculous mycobacteria had been collected from liquid culture
section during the study period. All isolates were identified by conventional
biochemical tests. A 441bp fragment of hsp65 genes was amplified and digested by
two restriction enzymes, BstEII and HaeIII. Digested products were analyzed using
polyacrilamid gel electrophoresis (PAGE). RESULTS: During study, 121 rapid grower
mycobacterial isolates were subjected for species identification. Isolates were
obtained from pulmonary samples (72) and extrapulmonary samples (49). In the PRA
test 8 different types of rapid grower mycobacteria were identified after
analyzing the fragments generated through restriction enzymes. Mycobacterium
chelonae (57/121) was the most common isolate in pulmonary and extrapulmonary
samples. Mycobacterium fortuitum (42), Mycobacterium abscessus (11),
Mycobacterium immunogen (06), Mycobacterium peregrinum (02), Mycobacterium
smegmatis (01), Mycobacterium wolinskyi (01), Mycobacterium goodii (01) were
identified as other species of rapid grower non tuberculous mycobacteria.
CONCLUSION: PRA is a rapid and accurate system for the identification of species
of non tuberculous mycobacteria. Results of PRA and biochemical tests are
concordant up to 98%.
PMID- 29332651
TI - Koch's postulates - Pitfalls and relevance in the 21st century.
PMID- 29332652
TI - Initial airflow obstruction in new cases of pulmonary tuberculosis: Complication,
comorbidity or missed?
AB - : Tuberculosis (TB) may have a similar spirometry findings as a chronic
obstructive pulmonary disease but the prevalence of TB-induced airflow
obstruction (AO) is still unknown. OBJECTIVES: To measure frequency of AO in new
TB cases at the beginning of treatment and to evaluate factors associated with
obstructive abnormalities following TB diagnosis. MATERIALS AND METHODS: 317
patients that have no history of prior AO were recruited into the study with a
median age of 39.0 years (IQR, 30.0-49.0). AO was defined using the
FEV1/F(VC)=18 years, N = 1011. MEASUREMENTS: A cross
sectional national online survey assessed diagnosed OSA, OSA symptoms, insomnia
symptoms, sleep problems, excessive daytime sleepiness (Epworth Sleepiness Scale
>=11), and physician-diagnosed health conditions (heart disease, diabetes,
hypertension, reflux disease, lung disease, depression, anxiety/panic disorder,
arthritis). Possible undiagnosed OSA was estimated using self-reported frequent
loud snoring and witness apneas. International Criteria for Sleep Disorders-3
criteria identified insomnia symptoms. Logistic regression models adjusted for
age, sex, obesity, and smoking determined correlates of sleep disorders. RESULTS:
Comorbid sleep conditions were common, with 56% of participants demonstrating >=1
condition. Reporting >=1 mental health condition (depression and/or anxiety) was
independently associated with diagnosed OSA (odds ratio [95% confidence interval
{CI}]: 6.6 [3.2-13.6]), undiagnosed OSA (3.2 [1.8-5.8]), simple snoring (2.4 [1.2
4.5]), insomnia symptoms (4.3 [2.5-7.3]), and restless legs (1.9 [1.2-3.1]).
Diagnosed OSA was significantly associated with >=1 cardiometabolic condition
(2.9 [1.4-6.0]) and arthritis (3.6 [1.8-7.2]). ESS >=11 was associated with
diagnosed (3.1 [1.4-6.8]) and undiagnosed OSA (6.2 [3.4-11.4]), insomnia symptoms
(2.6 [1.4-4.9]), and restless legs (2.3 [1.4-4.0]), and these sleep conditions
were also significantly associated with >=2 diagnosed medical problems.
CONCLUSION: Strategies to facilitate the diagnosis and management of often
comorbid sleep disorders in primary care are required to reduce the significant
sleep-related disparities in cardiometabolic and mental health.
PMID- 29332674
TI - Sleep apnea and pesticide exposure in a study of US farmers.
AB - INTRODUCTION: Carbamate and organophosphate pesticides inhibit
acetylcholinesterase, and poisoning leads to respiratory depression. Thus,
involvement in sleep apnea is plausible, but no data exist at lower levels of
exposure. Other pesticides could impact sleep apnea by different mechanisms but
have not been studied. Our study examines the associations between pesticide
exposure and sleep apnea among pesticide applicators from a US farming
population. PARTICIPANTS AND METHODS: We analyzed data from 1569 male pesticide
applicators, mostly farmers, from an asthma case-control study nested within the
prospective Agricultural Health Study. On questionnaires, participants reported
use of specific pesticides and physician diagnosis plus prescribed treatments for
sleep apnea. We used multivariable logistic regression to estimate associations
between ever use of 63 pesticides and sleep apnea (234 cases, 1335 noncases).
RESULTS: The most notable association was for carbofuran, a carbamate (100
exposed cases, odds ratio 1.83, 95% confidence interval 1.34-2.51, P=.0002).
Carbofuran use began before reported onset of sleep apnea in all cases.
DISCUSSION: This study adds to the known adverse health outcomes of exposure to
carbofuran, a pesticide canceled in the United States in 2009 for most
agricultural purposes but persists in the environment and remains in use in some
other countries. CONCLUSIONS: We conducted the first epidemiological study
investigating the association of pesticide exposure and sleep apnea. Our results
in a male agricultural population suggests that exposure to carbofuran is
positively associated with sleep apnea.
PMID- 29332675
TI - Sleep duration and incidence of type 2 diabetes: the Multiethnic Cohort.
AB - OBJECTIVES: As an emerging risk factor for the rising incidence of type 2
diabetes, we examined sleep duration in relation to type 2 diabetes and several
biomarkers. DESIGN: Prospective cohort recruited 1993-1996. SETTING: The
Multiethnic Cohort in Hawaii and California. PARTICIPANTS: A cohort of 151,691
White, African American, Japanese American, Native Hawaiian, and Latino
participants; 9695 cohort members had biomarker measurements. MEASUREMENTS: Sleep
duration was self-reported at cohort entry. Diabetes status was obtained from 3
questionnaires and confirmed by 3 administrative data sources. Biomarkers were
measured by standard assays 9.6+/-2.1 years after cohort entry. We estimated
diabetes risk as a time-varying outcome using Cox regression adjusted for body
mass index assessed at 3 time points and other known confounders and computed
adjusted means of biomarkers by sleep hours. RESULTS: During 7.9+/-3.5 years of
follow-up, 8487 new diabetes cases were diagnosed. Long sleep duration (>=9
hours), as compared with 7-8 hours, was significantly associated with higher
incidence (hazard ratio, 1.12; 95% confidence interval 1.04-1.21), but the 4%
elevated incidence for short sleep duration (<=6 hours) did not reach
significance (95% confidence interval 0.99-1.09). After stratification, the
associations appeared stronger in Japanese American than other ethnic groups and
in participants without comorbidity. Hours of sleep were positively associated
with C-reactive protein and triglycerides and inversely related to high-density
lipoprotein cholesterol and adiponectin but not with leptin levels and
homeostatic model assessment of insulin resistance. CONCLUSION: In this
multiethnic population, the 12% higher diabetes risk for long sleep hours may be
mediated through inflammation, a poor lipid profile, and lower adiponectin
levels.
PMID- 29332677
TI - Pilot study of sleep and meal timing effects, independent of sleep duration and
food intake, on insulin sensitivity in healthy individuals.
AB - This pilot study tested the independent and interactive effects of sleep and meal
times, under identical sleep duration and feeding conditions, on insulin
sensitivity (Si) in overweight adults. Participants underwent a 4-phase
randomized crossover inpatient study differing in sleep times: normal (Ns: 0000
0800 hours) or late (Ls: 0330-1130 hours); and in meal times: normal (Nm: 1, 5,
11, and 12.5 hours after awakening) or late (Lm: 4.5, 8.5, 14.5, and 16 hours
after awakening). An insulin-modified frequently sampled intravenous glucose
tolerance test, at scheduled breakfast time, and a meal tolerance test, at
scheduled lunch time, were performed to assess Si after 3 days in each condition.
Six participants were enrolled (4 men, 2 women; mean age 25.1+/-[SD] 3.9 years,
body mass index 29.2+/-2.7 kg/m2); only 1 failed to complete her last study
phase. There were no effects of sleep and meal times or sleep * meal time
interaction on Si (all P>.35), acute insulin response to intravenous glucose (all
P>.20), and disposition index (all P>.60) after adjusting for sex and body mass
index. Meal tolerance test glucose and insulin areas under the curve were lower
during Nm (glucose P=.11; insulin P=.0088). There were a sleep * meal interaction
and an effect of meal times on overnight glucose (P=.0040 and .012, respectively)
and insulin (P=.0075 and .067, respectively). Sleep timing, without concomitant
sleep restriction, does not adversely affect Si and glucose tolerance, but meal
times may be relevant for health. Our results should be confirmed in a larger
sample.
PMID- 29332678
TI - Relationship of sleep pattern and snoring with chronic disease: findings from a
nationwide population-based survey.
AB - OBJECTIVES: To investigate the association of total sleep time and presence or
absence of snoring with chronic disease among the Bangladeshi adult population.
DESIGN: Cross-sectional survey. SETTING: Urban and rural Bangladesh.
PARTICIPANTS: A total of 12,338 men and women aged >=35 years. MEASUREMENTS:
Total sleep time was considered as the total hours of sleep in 24 hours.
Furthermore, sleep time was categorized into <7, 7-9, and >9 hours according to
National Sleep Foundation (2015) guidelines. Self-reported snoring history was
captured and corroborated with their respective sleep partner/spouse in more than
80% cases. Registered physician-diagnosed current and/or previous cases of
hypertension, diabetes, coronary heart disease, cancer, stroke, chronic
obstructive pulmonary disease, and any other chronic conditions were counted.
RESULTS: Overall prevalence of at least 1 chronic disease in our study population
was around 18%: men (15.4%) and women (20.0%). Hypertension has the highest
prevalence (overall: 12.7%, men: 12.2%, women: 15%) followed by diabetes (4.9%),
coronary heart diseases (3.2%), stroke (1.8%), chronic obstructive pulmonary
disease (0.9%), and cancer (any type: 0.1%). Sleep pattern and snoring are
significantly associated with all individual chronic disease except cancer.
Sociodemographic, behavioral, and lifestyle variables were adjusted, and
inadequate total sleep time (<7 hours) and snoring (yes/no) showed significant
association with chronic disease status (risk ratio = 1.11, 95% confidence
interval 1.00-1.22 and risk ratio = 1.20, 95% confidence interval 1.11-1.29,
respectively). CONCLUSION: Inadequate sleep and snoring are independently
associated with chronic disease in Bangladeshi adult population and perhaps
elsewhere.
PMID- 29332680
TI - Sleep disorders + Pregnancy=Possibility of decreasing preterm births.
PMID- 29332679
TI - Socioeconomic status in childhood predicts sleep continuity in adult Black and
White men.
AB - OBJECTIVES: Low socioeconomic status (SES) in childhood may be associated with
sleep in adulthood. We evaluated the relationships between SES in childhood
through adolescence and into adulthood and sleep in midlife men. DESIGN:
Prospective assessment of SES in childhood and adulthood. SETTING: Population
based study of 139 Black and 105 White men enrolled since age 7 and evaluated for
sleep characteristics at age 32. MEASUREMENTS: Actigraphy and diary measures of
sleep duration, continuity, and quality for 1 week. Their parents reported their
SES (a combination of educational attainment and occupational status) annually
when the boys were ages 7 to 16. We estimated SES intercept (age 7) and slope
(age 7 to 16) using M-Plus and conducted linear regression analyses using those
values to predict adult sleep measures, adjusting for covariates. RESULTS: Men
who had lower SES families at age 7, smaller increases in SES from ages 7 to 16,
and lower SES in adulthood had more minutes awake after sleep onset. White men
with greater increases in SES from ages 7 to 16 had shorter sleep. CONCLUSIONS:
SES in childhood and improvement in SES through adolescence are related to sleep
continuity in midlife men. To our knowledge, this is the first report using
prospectively measured SES in childhood in relation to adult sleep.
PMID- 29332681
TI - Sleep duration, sleep quality, and sexual orientation: findings from the 2013
2015 National Health Interview Survey.
AB - INTRODUCTION: This study identifies associations between sleep outcomes and
sexual orientation net of sociodemographic and health-related characteristics,
and produces estimates generalizable to the US adult population.
PARTICIPANTS/METHODS: We used 2013-2015 National Health Interview Survey data
(46,909 men; 56,080 women) to examine sleep duration and quality among straight,
gay/lesbian, and bisexual US adults. Sleep duration was measured as meeting
National Sleep Foundation age-specific recommendations for hours of sleep per
day. Sleep quality was measured by 4 indicators: having trouble falling asleep,
having trouble staying asleep, taking medication to help fall/stay asleep (all
>=4 times in the past week), and having woken up not feeling well rested (>=4
days in the past week). RESULTS: In the adjusted models, there were no
differences by sexual orientation in the likelihood of meeting National Sleep
Foundation recommendations for sleep duration. For sleep quality, gay men were
more likely to have trouble falling asleep, to use medication to help fall/stay
asleep, and to wake up not feeling well rested relative to both straight and
bisexual men. Gay/lesbian women were more likely to have trouble staying asleep
and to use medication to help fall/stay asleep relative to straight women.
Finally, bisexual women were more likely to have trouble falling and staying
asleep relative to straight women. CONCLUSIONS: Sexual minority women and gay men
report poorer sleep quality compared with their straight counterparts.
PMID- 29332682
TI - A provisional tool for the measurement of sleep satisfaction.
AB - OBJECTIVES: The goal of this project was to provisionally identify the basic
elements of sleep satisfaction within the general population. METHODS: The
National Sleep Foundation conducted a systematic literature review and identified
495 published articles evaluating potential indicators of sleep satisfaction. The
National Sleep Foundation then convened an expert panel ("Panel"), provided full
text articles and summaries, and used a modified RAND appropriateness method with
three total rounds of voting to determine the appropriateness of indicators for
sleep satisfaction. RESULTS: The literature review revealed no tools or measures
of sleep satisfaction (not dissatisfaction) applied to the general population and
directly associated with good health. Nonetheless, a variety of sleep factors
were extracted from the extant sleep research literature. Panel members voted on
these indicators: sleep environmental factors; and sleep initiation and
maintenance parameters. Using these indicators, the Panel constructed provisional
questions for measuring sleep satisfaction. CONCLUSIONS: The Panel determined
that appropriate sleep satisfaction elements include how an individual feels (a)
about their sleep, (b) immediately after their sleep, and (c) during the
subsequent day. Additionally, appropriate environmental elements include (a)
bedding comfort, (b) bedroom temperature, and (c) noise and light in the bedroom.
How one feels with (a) the time it takes to fall asleep, (b) the ease with which
one falls back to sleep after awakening during a sleep period, (c) the amount of
sleep on weekdays and weekends, as well as how undisturbed one's sleep is also
were determined to be appropriate contributors to sleep satisfaction. Finally,
the Panel agreed that whether an individual desired to change anything about
their sleep, is a relevant question.
PMID- 29332683
TI - Insomnia in primary care-a study from India.
AB - OBJECTIVES: To study the prevalence and clinical correlates of insomnia among a
sample of primary care attendees, in the state of Kerala, India. DESIGN: Cross
sectional survey. SETTING: Primary care. PARTICIPANTS: 7017 adult patients [18-60
years] attending 71 primary health centers selected by cluster random sampling.
MEASUREMENTS: Patients were assessed for insomnia using the Insomnia Severity
Index. In addition to self-reported socio-demographic and chronic medical illness
details, structured instruments were used to assess for mental disorders,
disability and life satisfaction. RESULTS: Subclinical insomnia and clinical
insomnia were reported by 17.7% and 4.7% subjects, respectively. Subjects with
subclinical and clinical insomnia when compared to those without insomnia had
higher odds of having older age, female gender, urban background, lower
education, chronic medical and mental disorders, greater disability and poor life
satisfaction. Subjects with clinical insomnia when compared to the subclinical
group had higher odds of having older age, urban background, lower education,
mental disorders and greater disability. Among mental disorders, depressive
disorder was correlated with both clinical and subclinical insomnia. CONCLUSIONS:
Clinical and subclinical insomnia is common among primary care attendees and both
are associated with significant morbidity. This study highlights that it is a
major public health concern, albeit neglected, which needs to be dealt as a
priority.
PMID- 29332685
TI - Sleep patterns in children differ by ethnicity: cross-sectional and longitudinal
analyses using actigraphy.
AB - OBJECTIVES: To determine whether sleep patterns (duration, timing, efficiency)
differ by ethnicity. DESIGN: Longitudinal study. SETTING: Dunedin, New Zealand.
PARTICIPANTS: A total of 939 children (48% male) aged 4-12 years (572 European,
181 Maori, 111 Pacific, 75 Asian). MEASUREMENTS: All measurements were obtained
at months 0, 12, and 24. Anthropometry was obtained using standard techniques,
and parents completed questionnaires assessing demographics, dietary intake, and
television habits of children. Sleep and physical activity were measured using
Actigraph accelerometers over 1 week. Differences in sleep outcomes according to
ethnicity were adjusted for demographics, weight status, and behavioral variables
using mixed models. RESULTS: Pacific children had greater body mass index and
were more likely to live in deprived areas than children from other ethnic groups
(all P<.001), but few differences were observed in behavioral variables. Pacific
Island children slept 16 (95% confidence interval, 7-25) minutes less per night
than New Zealand European children, predominantly as a result of later bedtimes
(29; 20-38 minutes). By contrast, sleep efficiency did not differ by ethnicity or
over time (all P>=.118). Maori children did not show the same relative deficits
in sleep, displaying similar results to European children. Sleep duration
decreased by 8 minutes (95% confidence interval, 6-10) a night each year over 2
years, and change over time did not differ by ethnicity (all P>=.165).
CONCLUSIONS: From a young age, Pacific children had poorer sleep patterns than
European children, and these patterns were maintained over 2 years.
PMID- 29332684
TI - Racial/ethnic sleep disparities in US school-aged children and adolescents: a
review of the literature.
AB - Sleep is essential for optimal health, well-being, and cognitive functioning, and
yet nationwide, youth are not obtaining consistent, adequate, or high-quality
sleep. In fact, more than two-thirds of US adolescents are sleeping less than 8
hours nightly on school nights. Racial and ethnic minority children and
adolescents are at an increased risk of having shorter sleep duration and poorer
sleep quality than their white peers. In this review, we critically examined and
compared results from 23 studies that have investigated racial/ethnic sleep
disparities in American school-aged children and adolescents ages 6-19 years. We
found that White youth generally had more sufficient sleep than minority youth,
Hispanics had more than Blacks, and there was inconclusive evidence for Asians
and other minorities. Recommendations for researchers include the following: (1)
explore underlying causes of the disparities of these subpopulations, with a
particular interest in identifying modifiable causes; (2) examine factors that
may be impacted by racial/ethnic sleep disparities; (3) use a multidimensional
approach to measuring sleep disparities; and (4) examine how beliefs about sleep
are patterned by race/ethnicity. Understanding sleep disparities can inform
interventions, policies, and educational programs to minimize sleep disparities
and their impact on health, psychological, and educational outcomes.
PMID- 29332686
TI - No evidence for an epidemiological transition in sleep patterns among children: a
12-country study.
AB - OBJECTIVE: To examine the relationships between socioeconomic status (SES;
household income and parental education) and objectively measured sleep patterns
(sleep duration, sleep efficiency, and bedtime) among children from around the
world and explore how the relationships differ across country levels of human
development. DESIGN: Multinational, cross-sectional study from sites in
Australia, Brazil, Canada, China, Colombia, Finland, India, Kenya, Portugal,
South Africa, the United Kingdom, and the United States. SETTING: The
International Study of Childhood Obesity, Lifestyle and the Environment.
PARTICIPANTS: A total of 6040 children aged 9-11 years. MEASUREMENTS: Sleep
duration, sleep efficiency, and bedtime were monitored over 7 consecutive days
using waist-worn accelerometers. Multilevel models were used to examine the
relationships between sleep patterns and SES. RESULTS: In country-specific
analyses, there were no significant linear trends for sleep duration and sleep
efficiency based on income and education levels. There were significant linear
trends in 4 countries for bedtime (Australia, United States, United Kingdom, and
India), generally showing that children in the lowest income group had later
bedtimes. Later bedtimes were associated with lowest level of parental education
in only 2 countries (United Kingdom and India). Patterns of associations between
sleep characteristics and SES were not different between boys and girls.
CONCLUSIONS: Sleep patterns of children (especially sleep duration and
efficiency) appear unrelated to SES in each of the 12 countries, with no
differences across country levels of human development. The lack of evidence for
an epidemiological transition in sleep patterns suggests that efforts to improve
sleep hygiene of children should not be limited to any specific SES level.
PMID- 29332688
TI - Corrigendum to "Interaction between bacterial cell membranes and nano-TiO2
revealed by two-dimensional FTIR correlation spectroscopy using bacterial ghost
as a model cell envelope" [Water Res. 118 (2017) 104-113].
PMID- 29332687
TI - Similarities and differences in estimates of sleep duration by polysomnography,
actigraphy, diary, and self-reported habitual sleep in a community sample.
AB - OBJECTIVES: To compare estimates of sleep duration defined by polysomnography
(PSG), actigraphy, daily diary, and retrospective questionnaire and to identify
characteristics associated with differences between measures. DESIGN: Cross
sectional. SETTING: Community sample. PARTICIPANTS: The sample consisted of 223
Black, White, and Asian middle- to older-aged men and women residing in the
Pittsburgh, PA area. INTERVENTIONS: Not applicable. MEASUREMENTS: Two nights of
in-home PSG; 9 nights of wrist actigraphy and sleep diaries; retrospective sleep
questionnaires; and measures of sociodemographic, psychosocial, and adiposity
characteristics. RESULTS: All measures of sleep duration differed significantly,
with modest associations between PSG-assessed and retrospective questionnaire
assessed sleep duration. Individuals estimated their habitual sleep duration
about 20-30 minutes longer by questionnaire and their prospective sleep diaries
compared with both PSG- and actigraphy-assessed sleep duration. Persons reporting
higher hostility had smaller associations between PSG-assessed sleep duration and
other methods compared with those with lower hostility; those reporting more
depressive symptoms and poorer overall health had smaller associations between
actigraphy-assessed sleep duration and questionnaire and diary measures. Apnea
hypopnea index was not related to differences among estimates of sleep duration.
CONCLUSIONS: PSG, actigraphy, diary, and retrospective questionnaire assessments
yield different estimates of sleep duration. Hostility, depressive symptoms, and
perceptions of poor health were associated with the magnitude of differences
among some estimates. These findings may be useful in understanding the health
consequences of short or long self-reported sleep duration and for guiding
investigator decisions about choices of measures in specific populations.
PMID- 29332690
TI - Editorial.
PMID- 29332689
TI - Corrigendum to "Pesticides drive risk in wastewater-impacted streams during low
flow conditions " [Water Res. 110 (2017) 366-377].
PMID- 29332691
TI - Ink dating, part I: Statistical distribution of selected ageing parameters in a
ballpoint inks reference population.
AB - The development of ink dating methods requires an important amount of work in
order to be reliably applicable in practice. Major tasks include the definition
of ageing parameters to monitor ink ageing. An adequate parameter should ideally
fulfil the following criteria: it should evolve as a function of time in a
monotonic way, be measurable in a majority of ink entries, be as accurate and
reproducible as possible, and finally it should not be influenced too much by
transfer and storage conditions. This work aimed at evaluating the potential of
seven ageing parameters for ink dating purposes: the phenoxyethanol quantity,
relative peak areas (RPA), three solvent loss ratios (R%, R%*, NR%) and two
solvent loss parameters (RNORM, NRNORM). These were calculated over approximately
one year for 25 inks selected from a large database to represent different ageing
behaviours. Ink entries were analysed using liquid extraction followed by GC/MS
analysis. Results showed that natural ageing parameters (NR% and NRNORM) were not
suitable ageing parameters for ink entries older than a few weeks. RPA used other
compounds present in ink formulations in combination to PE in order to normalise
the results. However, it presented particular difficulties as they could not be
defined for all inks and were thus applicable only for 64% of the studied inks.
Finally, the PE quantity, R% and RNORM allowed to follow the ageing of the
selected inks over the whole time frame and were identified as the most
promising. These were thus selected to test three different interpretation models
in the second part of this article. The possibilities and limitations of ink
dating methods will be discussed in a legal perspective.
PMID- 29332692
TI - Dead weight: Validation of mass regression equations on experimentally burned
skeletal remains to assess skeleton completeness.
AB - In very fragmentary remains, the thorough inventory of skeletal elements is often
impossible to accomplish. Mass has been used instead to assess the completeness
of the skeleton. Two different mass-based methods of assessing skeleton
completeness were tested on a sample of experimentally burned skeletons with the
objective of determining which of them is more reliable. The first method was
based on a simple comparison of the mass of each individual skeleton with
previously published mass references. The second method was based on mass linear
regressions from individual bones to estimate complete skeleton mass. The
clavicle, humerus, femur, patella, metacarpal, metatarsal and tarsal bones were
used. The sample was composed of 20 experimentally burned skeletons from 10 males
and 10 females with ages-at-death between 68 and 90years old. Results
demonstrated that the regression approach is more objective and more reliable
than the reference comparison approach even though not all bones provided
satisfactory estimations of the complete skeleton mass. The femur, humerus and
patella provided the best performances among the individual bones. The
estimations based on the latter had root mean squared errors (RMSE) smaller than
300g. Results demonstrated that the regression approach is quite promising
although the patella was the only reasonable predictor expected to survive
sufficiently intact to a burning event at high temperatures. The mass comparison
approach has the advantage of not depending on the preservation of individual
bones. Whenever bones are intact though, the application of mass regressions
should be preferentially used because it is less subjective.
PMID- 29332693
TI - Ink dating part II: Interpretation of results in a legal perspective.
AB - The development of an ink dating method requires an important investment of
resources in order to step from the monitoring of ink ageing on paper to the
determination of the actual age of a questioned ink entry. This article aimed at
developing and evaluating the potential of three interpretation models to date
ink entries in a legal perspective: (1) the threshold model comparing analytical
results to tabulated values in order to determine the maximal possible age of an
ink entry, (2) the trend tests that focusing on the "ageing status" of an ink
entry, and (3) the likelihood ratio calculation comparing the probabilities to
observe the results under at least two alternative hypotheses. This is the first
report showing ink dating interpretation results on a ballpoint be ink reference
population. In the first part of this paper three ageing parameters were selected
as promising from the population of 25 ink entries aged during 4 to 304days: the
quantity of phenoxyethanol (PE), the difference between the PE quantities
contained in a naturally aged sample and an artificially aged sample (RNORM) and
the solvent loss ratio (R%). In the current part, each model was tested using the
three selected ageing parameters. Results showed that threshold definition
remains a simple model easily applicable in practice, but that the risk of false
positive cannot be completely avoided without reducing significantly the
feasibility of the ink dating approaches. The trend tests from the literature
showed unreliable results and an alternative had to be developed yielding
encouraging results. The likelihood ratio calculation introduced a degree of
certainty to the ink dating conclusion in comparison to the threshold approach.
The proposed model remains quite simple to apply in practice, but should be
further developed in order to yield reliable results in practice.
PMID- 29332694
TI - Score based procedures for the calculation of forensic likelihood ratios - Scores
should take account of both similarity and typicality.
AB - Score based procedures for the calculation of forensic likelihood ratios are
popular across different branches of forensic science. They have two stages,
first a function or model which takes measured features from known-source and
questioned-source pairs as input and calculates scores as output, then a
subsequent model which converts scores to likelihood ratios. We demonstrate that
scores which are purely measures of similarity are not appropriate for
calculating forensically interpretable likelihood ratios. In addition to taking
account of similarity between the questioned-origin specimen and the known-origin
sample, scores must also take account of the typicality of the questioned-origin
specimen with respect to a sample of the relevant population specified by the
defence hypothesis. We use Monte Carlo simulations to compare the output of three
score based procedures with reference likelihood ratio values calculated directly
from the fully specified Monte Carlo distributions. The three types of scores
compared are: 1. non-anchored similarity-only scores; 2. non-anchored similarity
and typicality scores; and 3. known-source anchored same-origin scores and
questioned-source anchored different-origin scores. We also make a comparison
with the performance of a procedure using a dichotomous "match"/"non-match"
similarity score, and compare the performance of 1 and 2 on real data.
PMID- 29332695
TI - Variation of delta2H, delta18O & delta13C in crude palm oil from different
regions in Malaysia: Potential of stable isotope signatures as a key traceability
parameter.
AB - A total of 33 crude palm oil samples were randomly collected from different
regions in Malaysia. Stable carbon isotopic composition (delta13C) was determined
using Flash 2000 elemental analyzer while hydrogen and oxygen isotopic
compositions (delta2H and delta18O) were analyzed by Thermo Finnigan TC/EA,
wherein both instruments were coupled to an isotope ratio mass spectrometer. The
bulk delta2H, delta18O and delta13C of the samples were analyzed by Hierarchical
Cluster Analysis (HCA), Principal Component Analysis (PCA) and Orthogonal Partial
Least Square-Discriminant Analysis (OPLS-DA). Unsupervised HCA and PCA methods
have demonstrated that crude palm oil samples were grouped into clusters
according to respective state. A predictive model was constructed by supervised
OPLS-DA with good predictive power of 52.60%. Robustness of the predictive model
was validated with overall accuracy of 71.43%. Blind test samples were correctly
assigned to their respective cluster except for samples from southern region.
delta18O was proposed as the promising discriminatory marker for discerning crude
palm oil samples obtained from different regions. Stable isotopes profile was
proven to be useful for origin traceability of crude palm oil samples at a
narrower geographical area, i.e. based on regions in Malaysia. Predictive power
and accuracy of the predictive model was expected to improve with the increase in
sample size. Conclusively, the results in this study has fulfilled the main
objective of this work where the simple approach of combining stable isotope
analysis with chemometrics can be used to discriminate crude palm oil samples
obtained from different regions in Malaysia. Overall, this study shows the
feasibility of this approach to be used as a traceability assessment of crude
palm oils.
PMID- 29332696
TI - A comparison of plastic cable ties based on physical, chemical and stable
isotopic measurements.
AB - Plastic cable ties can be utilised in a range of serious criminal activities and
a comparison of cable ties, or fragments, may form part of the physical evidence
presented to a Court of law. This research assessed the potential value of
evidence based on the analysis of plastic cable ties. Twenty packets of black
coloured plastic cable ties (nominally 200mm*4.8mm) were purchased in pack sizes
ranging from 25 to 100 individual cable ties (Brisbane, Australia, March 2015).
Representative samples from each packet were visually examined, compared and
tested to determine their physical dimensions, chemical compositions and stable
isotopic compositions (delta2H, delta13C and delta15N). All of the individual
cable ties from a given packet were found to be indistinguishable with respect to
appearance, physical, chemical and isotopic measurements (within-batch
variability). Individual cable ties were also found to be isotopically
homogeneous with respect to hydrogen, carbon and nitrogen. All of the cable ties
analysed were found to have very similar chemical compositions and to be
manufactured predominantly from nylon 6,6. The elemental compositions of
composite samples, prepared from each packet, were found to be highly variable
and, as such, were of very limited value. Cable ties from ten of the twenty
packets were uniquely characterised by physical appearance (between-batch
variability). Physical measurements such as the width, thickness and tooth-count
of the grip section did not provide additional discrimination. Cable ties from
nineteen of the twenty packets were uniquely characterised by isotopic
composition, based on delta2H and delta15N measurements. Samples from two packets
of Crescent brand cable ties were found to be indistinguishable with respect to
all of the tests applied in this study. These two packets were inadvertently
purchased from the same retailer and had the same barcode and batch number. It
was considered a reasonable assumption that these two packets originated from the
same manufacturing batch. The authors reason that a likelihood ratio (that might
be presented to a Court of law) can be derived from this type of discrete data
based on a calculation of the possible combinations of distinguishable objects
(unordered sampling with replacement) in a convenience sample collected from the
background population. In this example, a database of 19 distinguishable objects
can yield a likelihood ratio as high as 210, with a verbal equivalent of
"moderately strong support" for a proposition that two cable ties have the same
isotopic composition because they originate from the same batch rather than by
random chance.
PMID- 29332698
TI - Response to "A study of the perception of verbal expressions of the strength of
evidence".
PMID- 29332697
TI - Acid alteration of several ignitable liquids of potential use in arsons.
AB - Ignitable liquids such as fuels, alcohols and thinners can be used in criminal
activities, for instance arsons. Forensic experts require to know their chemical
compositions, as well as to understand how different modification effects could
impact them, in order to detect, classify and identify them properly in fire
debris. The acid alteration/acidification of ignitable liquids is a modification
effect that sharply alters the chemical composition, for example, of gasoline and
diesel fuel, interfering in the forensic analysis and result interpretation.
However, to date there is little information about the consequences of this
effect over other accelerants of interests. In this research paper, the
alteration by sulfuric acid of several commercial thinners and other accelerants
of potential use in arsons is studied in-depth. For that purpose, spectral (by
ATR-FTIR) and chromatographic (by GC-MS) data were obtained from neat and
acidified samples. Then, the spectral and chromatographic modifications of each
studied ignitable liquid were discussed, proposing several chemical mechanisms
that explain the new by-products produced and the gradual disappearance of the
initial compounds. Hydrolysis, Fischer esterification and alkylation reactions
are involved in the modification of esters, alcohols, ketones and aromatic
compounds of the studied ignitable liquids. This information could be crucial for
correctly identifying these accelerants. Additionally, an exploratory analysis
revealed that some of the most altered ignitable liquid samples might be very
similar with each other, which could have impact on casework.
PMID- 29332699
TI - Aiding the interpretation of forensic gait analysis: Development of a features of
gait database.
PMID- 29332700
TI - Corrigendum to "Preventing miscarriages of justice: A review of forensic firearm
identification" [Sci. Justice 56 (2) (2016) 129-142].
PMID- 29332701
TI - Editor's Perspectives - January 2018.
PMID- 29332702
TI - 2018, a turning point for the Archives de Pediatrie.
PMID- 29332703
TI - Commentary from the Editor.
PMID- 29332704
TI - Cutaneous squamous cell carcinoma: Incidence, risk factors, diagnosis, and
staging.
AB - Cutaneous squamous cell carcinoma (cSCC), a malignant proliferation of cutaneous
epithelium, represents 20% to 50% of skin cancers. Although the majority of cSCCs
are successfully eradicated by surgical excision, a subset of cSCC possesses
features associated with a higher likelihood of recurrence, metastasis, and
death. The proper identification of these aggressive cSCCs can guide additional
work-up and management. In the first article in this continuing medical education
series, we discuss the incidence, recurrence rates, mortality rates, and risk
factors associated with cSCC and review the staging systems used to stratify
patients into high- and low-risk groups. The second article in this series
reviews the treatment options for cSCC, with focused attention on the management
of high-stage tumors.
PMID- 29332705
TI - Cutaneous squamous cell carcinoma: Management of advanced and high-stage tumors.
AB - While the majority of cutaneous squamous cell carcinomas (cSCCs) can be treated
surgically, the additional work-up and treatments indicated for high-risk cSCC
remain undefined. In recent years, improvements in tumor staging systems have
allowed for the more accurate stratification of tumors into high- and low-risk
categories. This insight, along with the publication of cSCC guidelines, brings
us closer to the development of a consensus approach. The second article in this
continuing medical education series addresses in question and answer format the
most common questions related to advanced and high-stage cSCCs, with a simplified
flowchart. The questions include the following: 1) Does my patient have high-risk
cSCC?; 2) What is the next step for patients with cSCC and palpable
lymphadenopathy?; 3) In patients with no clinically evident lymphadenopathy, who
are candidates for lymph node staging?; 4) What forms of radiologic imaging can
help detect subclinical lymph node metastases?; 5) What is the role of sentinel
lymph node biopsy in cSCC?; 6) Which patients with cSCC need adjuvant radiation
therapy?; 7) Is adjuvant chemotherapy an option for patients with high-stage cSCC
after surgery?; 8) Are targeted and immunologic therapies an option for advanced
cSCC?; 9) How often should I follow up with my patient after he/she has been
diagnosed with a high-risk cSCC?; 10) What are the options for chemoprophylaxis
in a patient with an increased risk of cSCC?; and 11) What chemopreventive
measures can be started in coordination with medical oncology or transplant
physicians?
PMID- 29332706
TI - Skin mapping for the classification of generalized morphea.
AB - BACKGROUND: Generalized morphea lacks cohesive clinical features, limiting its
clinical and investigative utility. OBJECTIVE: We sought to use computerized
lesion mapping to objectively subtype morphea. METHODS: We conducted a 2-part
cross-sectional study. In part 1, we created a discovery cohort of patients with
generalized morphea of whom lesion maps were created to characterize subsets.
Clinical and demographic features were compared between proposed subsets to
determine if they identified clinically relevant differences. In part 2, we
created a validation cohort to determine if proposed criteria were applicable to
different individuals. RESULTS: A total of 123 patients with generalized morphea
were included. Mapping produced 2 distribution patterns that encompassed the
majority in both cohorts: isomorphic (areas of skin friction) and symmetric
(symmetrically distributed on trunk/extremities). In the discovery cohort, the
isomorphic subset was older (55.6 +/- 12.7 vs 42.2 +/- 20.1 years, P < .001), all
female (30/30 vs 38/43, P = .05), and more often had lichen sclerosus changes
(12/43 vs 8/43, P = .02); involvement of the reticular dermis, subcutaneous fat,
and/or fascia was more common in symmetric (10/43 vs 1/30) (P = .02). These
features persisted in the validation cohort. LIMITATIONS: Single cohort was a
limitation. CONCLUSIONS: Symmetric and isomorphic subsets possess distinctive
demographic and clinical features, suggesting they more accurately define the
phenotype of generalized morphea. Consideration should be given to revising
classification.
PMID- 29332707
TI - Cutaneous hemophagocytosis: Clinicopathologic features of 21 cases.
AB - BACKGROUND: Hemophagocytosis is well known in cytotoxic cutaneous T-cell
lymphomas (CTCLs), in which it may represent a sign of hemophagocytic
lymphohistiocytosis syndrome (HLHS), and is also typical of cutaneous Rosai
Dorfman disease (cRDD) (without prognostic relevance). Only rarely, has cutaneous
hemophagocytosis (CH) been described in other skin conditions. OBJECTIVE: To
characterize the clinicopathologic features of CH in skin biopsy specimens from
patients with conditions other than CTCL or cRDD. METHODS: Case series analyzing
clinicopathologic features and follow-up data on patients presenting with
histopathologic signs of CH. RESULTS: Biopsy specimens from 21 patients were
included. None of the patients had HLHS. The majority (n = 11) presented with
leukocytoclastic vasculitis. Other associated diseases were lupus erythematous (n
= 2), arthropod bite reaction (n = 2), erysipelas (n = 1), acne conglobata (n =
1), and Sweet syndrome (n = 1). Three patients had a nonspecific rash concomitant
with Chlamydia pneumonia, middle ear infection, and pharyngitis, respectively.
LIMITATIONS: This was a single-center, retrospective study. CONCLUSION: Isolated
CH in conditions other than CTCL and cRDD is a histopathologic finding related
mostly to leukocytoclastic vasculitis. Extensive investigations should be
performed only if patients have other signs or symptoms of HLHS.
PMID- 29332709
TI - Epidemiology of staphylococcal scalded skin syndrome in the United States: A
cross-sectional study, 2010-2014.
PMID- 29332710
TI - Socioeconomic and geographic barriers to dermatology care in urban and rural US
populations.
PMID- 29332708
TI - Management of psoriasis in patients with inflammatory bowel disease: From the
Medical Board of the National Psoriasis Foundation.
AB - BACKGROUND: There is a significant association between psoriasis and inflammatory
bowel disease (IBD). Many treatments for psoriasis and psoriatic arthritis are
also used for IBD. OBJECTIVE: To assess therapeutic options for patients with
psoriasis and concurrent IBD. METHODS: A systematic literature search was
performed for clinical studies of biologic and systemic psoriasis medications in
psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn's disease, for the
period from January 1, 1947, to February 14, 2017. Randomized, controlled, double
blinded studies were selected if available. If not, the next highest level of
available evidence was selected. RESULTS: Of the 2282 articles identified, 132
were selected. Infliximab and adalimumab have demonstrated efficacy in psoriasis,
psoriatic arthritis, ulcerative; colitis, and Crohn's disease. Ustekinumab has
demonstrated efficacy in psoriasis, psoriatic arthritis, and Crohn's disease.
Certolizumab has demonstrated efficacy in psoriatic arthritis and Crohn's
disease. Etanercept, secukinumab, brodalumab, and ixekizumab have demonstrated
efficacy in psoriasis and psoriatic arthritis but may exacerbate or induce IBD.
Guselkumab has demonstrated efficacy in psoriasis. LIMITATIONS: There are no
known clinical trials of treatment specifically for concurrent psoriasis and IBD.
CONCLUSIONS: Infliximab and adalimumab have demonstrated efficacy in psoriasis,
psoriatic arthritis, ulcerative colitis, and Crohn's disease; other agents have
demonstrated efficacy for some, but not all, of these indications.
PMID- 29332711
TI - Very low-dose versus standard dose radiation therapy for indolent primary
cutaneous B-cell lymphomas: A retrospective study.
PMID- 29332712
TI - Differences between recruitment advertisements for academic and private practice
dermatologists.
PMID- 29332713
TI - Fissured tongue in patients with psoriasis.
PMID- 29332714
TI - Oral green tea catechins do not provide photoprotection from direct DNA damage
induced by higher dose solar simulated radiation: A randomized controlled trial.
PMID- 29332715
TI - Prevalence of gastrointestinal comorbidities in rosacea: Comparison of
subantimicrobial, modified release doxycycline versus conventional release
doxycycline.
PMID- 29332717
TI - Patch testing for nonimmediate cutaneous adverse drug reactions.
PMID- 29332716
TI - Predicting the incidence and timing of central nervous system disease in
metastatic melanoma: Implications for surveillance and preventative therapy.
PMID- 29332718
TI - Accuracy of death certification in cutaneous squamous cell carcinoma: A
retrospective case review.
PMID- 29332719
TI - The ethics of volunteerism: Whose cultural and ethical norms take precedence?
PMID- 29332720
TI - Commentary: The ethics of volunteerism: Whose cultural and ethical norms take
precedence?
PMID- 29332721
TI - Oral isotretinoin as an adjunctive treatment for recurrent genital warts.
PMID- 29332722
TI - From laboratory to operating room: Innovative use of manual blood cell counting
machine for counting follicular grafts.
PMID- 29332723
TI - A method using simple stitches around the safety margin for hemostasis in scalp
surgery.
PMID- 29332724
TI - Reply to: "Tofacitinib for the treatment of severe alopecia areata and variants".
PMID- 29332725
TI - In reply.
PMID- 29332726
TI - Histopathology of facial papules in frontal fibrosing alopecia and therapeutic
response to oral isotretinoin.
PMID- 29332727
TI - Reply to: "Histopathology of facial papules in frontal fibrosing alopecia and
therapeutic response to oral isotretinoin".
PMID- 29332728
TI - Is the setting sun dermoscopic pattern specific to juvenile xanthogranuloma?
PMID- 29332729
TI - Reply to: "Is the setting sun dermoscopic pattern specific to juvenile
xanthogranuloma?"
PMID- 29332730
TI - Biomechanical factors associated with running economy and performance of elite
Kenyan distance runners: A systematic review.
AB - BACKGROUND: Running economy (RE) is a determinant of performance in endurance
sports and is a complex multi-factorial measure which reflects the combined
functioning of bio-mechanical, neuro-muscular, metabolic and cardio-respiratory
factors some of which are hereditary or adapt to coaching. Kenyan distance
runners have dominated major global events with their unmatched performance for
decades and this phenomenon has prompted several investigations aimed at
establishing possible factors associated with their performance. This systematic
review was aimed at establishing up-to date quantitative synthesis of evidence on
biomechanical factors associated with running economy and performance of elite
Kenyan distance runners and to provide an algorithm for future research and
coaching strategies. METHODS: A comprehensive electronic search was conducted
through June 2017. Quality appraisal was independently done by both reviewers
using the STROBE checklist. Descriptive summaries and tables were used to
illustrate biomechanical outcomes, mean differences and confidence intervals.
Evidence from reviewed studies was graded according to the Australian National
Health and Medical Research Council (NHMRC) hierarchy for aetiological factors
and meta-analysis was performed where applicable. RESULTS: Eight cross-sectional
studies were included. The overall methodological score was moderate (58%). Elite
Kenyan distance runners have significant longer gastroc-Achilles tendons compared
to their counterparts while their shank length is not significantly longer. There
is no certainty of evidence regarding the association between their
characteristic unique profile of tall and slender bodies, low BMI and low body
mass, short ground contact and flight times, greater forward lean torso and
faster and greater forward leg swing with RE and performance. CONCLUSION: Our
findings presents evidence on biomechanical factors associated with RE and
performance of elite Kenyan distance runners. Despite these findings, there are a
number of limitations inherent to this review including; low level of evidence,
minimal number of included studies, small sample size and lack of appropriate
control subjects. However, we considered these shortcomings and summarised the
best available evidence in attempt to give direction to future research and
coaching strategies.
PMID- 29332731
TI - Quantitative tissue parameters of Achilles tendon and plantar fascia in healthy
subjects using a handheld myotonometer.
AB - OBJECTIVE: The aim of the study was to examine the quantitative tissue properties
of the Achilles tendon and plantar fascia using a handheld, non-invasive
MyotonPRO device, in order to generate normal values and examine the
biomechanical relationship of both structures. DESIGN: Prospective study of a
large, healthy sample population. PARTICIPANTS: The study sample included 207
healthy subjects (87 males and 120 females) for the Achilles tendon and 176
healthy subjects (73 males and 103 females) for the plantar fascia. For the
correlations of the tissue parameters of the Achilles tendon and plantar fascia
an intersection of both groups was formed which included 150 healthy subjects (65
males and 85 females). INTERVENTIONS: All participants were measured in a prone
position. Consecutive measurements of the Achilles tendon and plantar fascia were
performed by MyotonPRO device at defined sites. RESULTS: For the left and right
Achilles tendons and plantar fasciae all five MyotonPRO parameters (Frequency
[Hz], Decrement, Stiffness [N/m], Creep and Relaxation Time [ms]) were calculated
of healthy males and females. The correlation of the tissue parameters of the
Achilles tendon and plantar fascia showed a significant positive correlation of
all parameters on the left as well as on the right side. CONCLUSIONS: The
MyotonPRO is a feasible device for easy measurement of passive tissue properties
of the Achilles tendon and plantar fascia in a clinical setting. The generated
normal values of the Achilles tendon and plantar fascia are important for
detecting abnormalities in patients with Achilles tendinopathy or plantar
fasciitis in the future. Biomechanically, both structures are positively
correlated. This may provide new aspects in the diagnostics and therapy of
plantar fasciitis and Achilles tendinopathy.
PMID- 29332732
TI - The science of respiratory characteristics in individuals with chronic low back
pain: Interpreting through statistical perspective.
PMID- 29332733
TI - A fundamental critique of the fascial distortion model and its application in
clinical practice.
AB - INTRODUCTION: The therapeutic techniques used in the fascial distortion model
(FDM) have become increasingly popular among manual therapists and physical
therapists. The reasons for this trend remain to be empirically explored.
Therefore this paper pursues two goals: first, to investigate the historical and
theoretical background of FDM, and second, to discuss seven problems associated
with the theory and practice of FDM. MATERIALS AND METHODS: The objectives of
this paper are based on a review of the literature. The research mainly focuses
on clinical proofs of concept for FDM treatment techniques in musculoskeletal
medicine. RESULTS: FDM as a treatment method was founded and developed in the
early 1990s by Stephen Typaldos. It is based on the concept that all
musculoskeletal complaints can be traced back to three-dimensional deformations
or distortions of the fasciae. The concept is that these distortions can be
undone through direct application of certain manual techniques. A literature
review found no clinical trials or basic research studies to support the
empirical foundations of the FDM contentions. DISCUSSION: Based on the absence of
proof of concept for FDM treatment techniques along with certain theoretical
considerations, seven problems emerge, the most striking of which include (1)
diagnostic criteria for FDM, (2) the biological implausibility of the model, (3)
the reduction of all such disorders to a single common denominator: the fasciae,
(4) the role of FDM research, and (5) potentially harmful consequences related to
FDM treatment. CONCLUSION: The above problems can only be invalidated through
high-quality clinical trials. Allegations that clinical experience is sufficient
to validate therapeutic results have been abundantly refuted in the literature.
PMID- 29332734
TI - Correlation between cervical flexor muscle thickness and craniocervical flexion
torque in healthy subjects.
AB - The purpose of this study was to clarify the relationship between the size of the
cervical flexor muscles and craniocervical (CC) flexion torque. Thirty-eight
healthy men participated in this study. Thickness of the deep cervical flexor
(DCF) and sternocleidomastoid (SM) muscles were measured using ultrasonography.
Maximal isometric CC flexion torque was measured using dynamometry. The DCF and
SM muscle thickness and CC flexion torque were normalized relative to body
weight. Correlations between normalized muscle thickness and normalized CC
flexion torque were determined. A significant positive correlation was observed
between normalized DCF muscle thickness and normalized CC flexion torque (r =
0.361, P = 0.028), whereas there was no significant correlation between
normalized SM muscle thickness and normalized CC flexion torque (r = 0.233, P =
0.166). DCF muscle thickness appears to have potential clinical application in
the performance of CC flexion.
PMID- 29332735
TI - Within-day and between-day reliability of thickness measurements of abdominal
muscles using ultrasound during abdominal hollowing and bracing maneuvers.
AB - Ultrasonography imaging has been used as a non-invasive method to estimate the
thickness and relative activities of the abdominal muscles in patients with lower
back pain (LBP). However, the statistical reliability of US thickness
measurements of abdominal muscles, including transversus abdominis (TrA),
internal oblique (IO) and external oblique (EO) muscles during abdominal
hollowing (AH) and abdominal bracing (AB) maneuvers has not been well
investigated. This study was performed on a total of 20 female subjects (10 with
LBP and 10 without LBP) in the age range of 25-55 years to assess within-day and
between-day reliability of the measurements. US measurements on maneuvers were
repeated after two hours for the within-day reliability and after five days for
the between-day reliability assessment. High intra-class correlation coefficient
(ICC) values (>0.75) for within-day and between-day reliability assessments
during AH maneuver were concluded. The ICC values were moderate for reliability
assessment during AB. The ICC values for AH were greater than AB both for within-
and between-day reliabilities. The small standard error of measurement and
minimal detectable change values (0.16-0.78 and 0.44 to 2.15, respectively) were
found for both AH and AB. We recommend real-time US imaging as a reliable way of
determining the thicknesses of the TrA and IO muscle (and to some extent, EO
muscle) for both healthy and LBP patients.
PMID- 29332736
TI - Electromyographic changes in muscles around the ankle and the knee joints in
women accustomed to wearing high-heeled or low-heeled shoes.
AB - OBJECTIVES: This study aimed to investigate muscle activities in the muscles
around the ankle and knee joints in women accustomed to wearing high-heeled or
low-heeled shoes. METHODOLOGY: Forty young women (age: 18-40 years) participated
in this comparative clinical study. Twenty of the recruited subjects were
accustomed to high-heeled shoes and the other half to low-heeled shoes.
Electrical activities of the ankle and knee muscles in both groups with and
without wearing their accustomed shoes were studied during walking. RESULTS:
Tibialis anterior and the medial gastrocnemius muscles started contraction
earlier in the high-heeled shoe group. The duration of medial gastrocnemius
activity and the intensity of proneus longus activity were significantly more in
the high-heeled shoe group. CONCLUSION: Wearing high-heeled shoe for a long time
could result in over work of muscles such as medial gastrocnemius and proneus
longus by increasing the duration or the intensity of their contractions during
walking.
PMID- 29332737
TI - Effect of a lateral glide mobilisation with movement of the hip on vibration
threshold in healthy volunteers.
AB - BACKGROUND: Mulligan's mobilisation-with-movement (MWM) techniques are proposed
to achieve their clinical benefit via neurophysiological mechanisms. However,
previous research has focussed on responses in the sympathetic nervous system
only, and is not conclusive. An alternative measure of neurophysiological
response to MWM is required to support or refute this mechanism of action.
Recently, vibration threshold (VT) has been used to quantify changes in the
sensory nervous system in patients experiencing musculoskeletal pain. OBJECTIVE:
To investigate the effect of a lateral glide MWM of the hip joint on vibration
threshold compared to a placebo and control condition in asymptomatic volunteers.
METHODS: Fifteen asymptomatic volunteers participated in this single-blinded,
randomised, within-subject, placebo, control design. Participants received each
of three interventions in a randomised order; a lateral glide MWM of the hip
joint into flexion, a placebo MWM, and a control intervention. Vibration
threshold (VT) measures were taken at baseline and immediately after each
intervention. Mean change in VT from baseline was calculated for each
intervention and then analysed for between group differences using a one-way
analysis of variance (ANOVA). RESULTS: A one-way ANOVA revealed no statistically
significant differences between the three experimental conditions (P = 0.812).
CONCLUSION: This small study found that a lateral glide MWM of the hip did not
significantly change vibration threshold compared to a placebo and control
intervention in an asymptomatic population. This study provides a method of using
vibration threshold to investigate the potential neurophysiological effects of a
manual therapy intervention that should be repeated in a larger, symptomatic
population.
PMID- 29332738
TI - Body composition estimation in children and adolescents by bioelectrical
impedance analysis: A systematic review.
AB - BACKGROUND: Bioelectrical impedance analysis (BIA) has commonly been used to
assess the body composition of children and adolescents. BIA validation studies
have found distinct correlation values with reference methods. OBJECTIVES: To
assess the reproducibility, correlation and mean differences in body composition
estimated by BIA and reference methods, we systematically reviewed the literature
in the pediatric population. METHOD: The search for articles was conducted in
March 2016 and was limited to articles published from 2005 to 2015 in the PubMed,
Embase, EBSCO, Web of Science, Scopus and SciELO databases. Two reviewers
independently performed data selection and extraction of studies that
investigated the BIA validity, responsiveness, reliability and/or measurement
error (reproducibility) to estimate body composition in children and adolescents
with an average age <= 18 years. RESULTS: The search produced 48 articles. Almost
perfect reproducibility was found in the body fat percentage estimated by BIA,
and there was almost perfect correlation between the BIA ratings and reference
methods for fat mass and fat-free mass. Regarding component estimates, BIA
underestimated the fat mass in both sexes. CONCLUSIONS: The body fat percentage
estimated by BIA exhibited almost perfect reproducibility. The fat mass and fat
free mass estimated by BIA correlated almost perfectly with the reference methods
in both sexes. BIA underestimated the fat mass in both sexes.
PMID- 29332739
TI - Multifidus muscle size in adolescents with and without back pain using
ultrasonography.
AB - OBJECTIVE: The purposes of this study were; a) to compare multifidus muscle cross
sectional area (CSA) in male adolescents suffering from low back pain (LBP) with
healthy male adolescents using ultrasonography (US), and b) to assess the
correlation between multifidus muscle size and demographic variables. METHODS: A
random sample of 40 healthy boys (as a control group) and 40 boys with LBP (as an
experimental group) at the age range of 15-18 years was recruited in the present
cohort study. Multifidus muscle dimensions including CSA, antero-posterior and
medio-lateral dimensions were measured at level of L5 in both groups using US.
RESULTS: The results of an independent t-test to compare multifidus muscle size
between the experimental and control groups showed a significant difference
between the two groups in terms of CSA, antro-posterior and medio-lateral
dimensions so that the experimental group had smaller muscle size than the
control group. A significant correlation was found between height, weight and
body mass index (BMI) and multifidus muscle size, but no significant correlation
was observed between age and muscle size. Pain intensity and functional
disability index was significantly correlated with muscle size in the
experimental group. CONCLUSIONS: According to the results, multifidus muscle size
was decreased in 15-18 years old male adolescents suffering from LBP compared
with their healthy counterparts. Further studies are needed to support the
findings of the present study.
PMID- 29332740
TI - An electromyographic analysis of selected asana in experienced yogic
practitioners.
AB - The purpose of this study was to assess electromyographic (EMG) output of the
anterior tibialis (TA), medial head of the gastrocnemius (GA), rectus femoris
(RF), bicep femoris (BF), and gluteus medius (GM) in experienced yogic
practitioners during selected yoga asana. A secondary purpose was to examine the
differences in EMG output in unilateral V. bilateral standing yoga asana. The
study was a single occasion descriptive design. Thirteen healthy yoga
practitioners (1 male, 12 females, average age of 37.5) with more than five years
of experience were recruited. EMG activity was recorded during maximum voluntary
isometric contractions (MVIC) of the TA, GA, RF, and BF using the Biodex
Multijoint System(r), and GM using manual muscle testing position. Subjects then
performed the following yoga asana while EMG activity was recorded: downward
facing dog, half-moon, tree, chair, and warrior three pose. Each asana was held
for fifteen seconds and performed three times. EMG data were band pass filtered
and the root mean square was obtained. Asana data were then amplitude normalized
with the subjects' MVIC data. Integrated EMG was calculated for TA, GA, RF, BF
and GM, in each asana. A multilevel regression analysis was performed, and peak
EMG data was compared. Analysis between muscles showed that during CH and DD EMG
activity was greatest in the TA muscle compared to the other muscles, while
during HM and WR the GA muscle showed the greatest activity. Analysis within
muscles showed low GA, BF, and GM activity during chair pose and downward facing
dog compared to half moon, tree, and warrior three, and high RF activity during
chair compared to the other poses. In conclusion, there were differences in
frontal and sagittal plane muscle activation between single limb and double limb
poses in experienced yogic practitioners.
PMID- 29332741
TI - Abdominal and pelvic floor electromyographic analysis during abdominal
hypopressive gymnastics.
AB - INTRODUCTION: Abdominal hypopressive gymnastics appeared as an alternative to
traditional abdominal exercises to promote abdominal muscles strength without
overloading the pelvic floor muscles (PFM). To determine the activation level of
abdominal muscles and PFM and the posture influence in the level of activation in
these muscles during abdominal hypopressive gymnastics, we used surface
electromyography in young and healthy multipara women. METHODS: This is an
observational study with eutrophic nulliparous women aged between 18 and 35
years, with abdominal skinfold less than or equal to 3 cm and active or
irregularly active physical activity. Surface electromyography was used for
rectus abdominis, external oblique, transversus abdominal/internal oblique
(TrA/IO) and PFM assessment in the supine, quadruped and orthostatic (upright
standing) positions during abdominal hypopressive gymnastics using normalized
electromyographic (%EMG) data. We also analyzed the difference in activation
between each muscle and between muscles and positions. RESULTS: Thirty women were
evaluated and the mean age was 25.77 years (SD 3.29). The group formed by the
TrA/IO muscles and the PFM showed higher %EMG in all the positions assessed,
followed by the external oblique and rectus abdominis muscles. A comparison of
%EMG of each muscle between the different positions showed differences only in
rectus abdominis between the supine and quadruped (p = 0.001) and supine and
orthostatic positions (p = 0.004), and in TrA/IO between the supine and
orthostatic (p = 0.023) and orthostatic and quadruped positions (p = 0.019).
CONCLUSIONS: The results suggest that abdominal hypopressive gymnastics can
activate the abdominal muscles and PFM and the position do not have influence on
electromyographic activation level of the PFM and external oblique.
PMID- 29332742
TI - The effects of dorso-lumbar motion restriction on EMG activity of selected
muscles during running.
AB - : The effects of restricting dorso-lumbar spine mobility on electromyographic
activity of the erector spinae, quadriceps femoris, hamstrings and gastrocnemius
muscles in runners was investigated. Thermoplastic casting material was fashioned
into a rigid orthosis and used to restrict spinal motion during running.
Volunteers ran on a treadmill at 2.78 m/sec, under normal conditions and with
spinal motion restricted. Surface electromyographic data was collected during
both sets of trials. Normal electromyographic data was also compared with
previous authors to determine similarity with their electromyographic data.
RESULTS: Casted running resulted in an increase in erector spinae (p < 0.01) and
quadriceps femoris (p = 0.02) electromyography activity. Total stride time and
swing time of gait were decreased during casted running (p < 0.01), indicating a
shift towards shorter and thus more frequent steps to run the same distance. The
normal electromyographic data collected was in agreement with previously reported
work. CONCLUSIONS: Neurological control over muscle and the fascia surrounding it
is responsible for joint movement and load transfer. Experimentally restricting
spinal motion during running demonstrated an increase in erector spinae and
rectus femoris electromyographic activity. This lends support to the hypothesis
that decreased spinal mobility may be a contributing factor to overuse muscle
injuries in runners.
PMID- 29332743
TI - Myoeletric indices of fatigue adopting different rest intervals during leg press
sets.
AB - INTRODUCTION: The purpose of this study was to examine the acute effect of
different rest intervals between multiple sets of the 45 degrees angled leg
press exercise (LP45) on surface electromyographic (SEMG) spectral and amplitude
indices of fatigue. METHODS: Fifteen recreationally trained females performed
three protocols in a randomized crossover design; each consisting of four sets of
10 repetitions with 1 (P1), 3 (P3), or 5 (P5) minute rest intervals between sets.
Each set was performed with 70% of the LP45 ten-repetition maximum load. The SEMG
data for biceps femoris (BF), vastus lateralis (VL), vastus medialis (VM), and
rectus femoris (RF) muscles was then evaluated. RESULTS: The SEMG amplitude
change in the time coefficient (CRMS) and spectral fatigue index (Cf5) indicated
higher levels of fatigue for all muscles evaluated during the P3 protocol versus
the P1 and P5 protocols (p <= 0.05), respectively. The RF and VL muscles showed
greater fatigue levels by the second and third sets; whereas, greater fatigue was
shown in the VM and BF muscles by the fourth set (p <= 0.05). CONCLUSIONS: A
three-minute rest interval between sets might represent a neuromuscular window
between a fatigue stated and fully recovered state in the context of neural
activation. Moreover, a three minute rest interval between sets might allow for
consistent recruitment of high threshold motor units over multiple sets, and thus
promote a more effective stimulus for strength gains.
PMID- 29332744
TI - How many physical therapy sessions are required to reach a good outcome in
symptomatic lumbar spondylolisthesis? A retrospective study.
AB - BACKGROUND: There is a lack of conclusive information about the optimal dosage of
physical therapy treatments in Spondylolisthesis (SPL) patients. PURPOSE: The
present study attempted to evaluate the comparative effectiveness of two
different doses in reaching similar clinical outcomes. METHODS: A retrospective
cohort study of 64 consecutive patients admitted for physical therapy with
symptomatic lumbar grade I SPL (42 +/- 15years, 57% female) was conducted. At the
end of the treatment, all participants were retrospectively assigned to one of
two groups, receiving either 5-8 or 9-12 sessions (experimental or control group,
respectively) of physical therapy treatments. The Prone Bridge Test (PBT) and the
Supine Bridge Test (SBT) were used to measure muscular endurance. RESULTS: The
area under the ROC curve for the PBT was 0.64 (95% CI 0.45-0.83) and for the SBT
was 0.57 (95% CI 0.33-0.80). The optimal cutoff points were 25.5s for the PBT and
55.0s for the SBT. Logistic regression revealed that PBT (OR = 1.062) was
associated with SPL. The final regression model explained 77.4% (R2 = 0.341; p =
0.024) of the variability. CONCLUSIONS: In this sample, the number of sessions
required to achieve satisfactory outcomes ranged from 5 to 12. The clinical
results of the subjects in the 5-8 sessions group were similar to the 9-12
sessions group. Individual's coping mechanisms could be considered in future
studies to understand which patients will require more therapeutic sessions.
PMID- 29332745
TI - A critical overview of the current myofascial pain literature - January 2018.
AB - The majority of papers included in the quarterly review discuss various aspects
of dry needling (DN), which continues to be of interest to researchers and
clinicians. A study by Liu et al. is the first paper to examine the effects of DN
of acetylcholine, esterase and receptors. The study provides support for the
integrated trigger point hypothesis and for DN. A paper by Hightower and
colleagues found an intriguing link between low magnesium levels in the drink
water supply, vitamin D, and myofascial pain, cancer, tendon ruptures, and colon
polyps. Contributions originated in the Brazil, China, Germany, Iran, India,
Poland, South Korea, Spain, Taiwan, Turkey, and the US.
PMID- 29332746
TI - Is Pilates an effective rehabilitation tool? A systematic review.
AB - BACKGROUND: Pilates is a system of exercise focusing upon controlled movement,
stretching and breathing. Pilates is popular today not only for physical fitness
but also for rehabilitation programs. This paper is a review of the literature on
the effectiveness of Pilates as a rehabilitation tool in a wide range of
conditions in an adult population. METHODS: A systematic literature review was
carried out according to the PRISMA guidelines. Electronic databases were
searched for cohort studies or randomised controlled trials (RCTs), and inclusion
and exclusion criteria were applied. The final RCTs were assessed using the PEDro
and CONSORT 2010 checklists. RESULTS: Twenty-three studies, published between
2005 and 2016, met the inclusion criteria. These papers assessed the efficacy of
Pilates in the rehabilitation of low back pain, ankylosing spondylitis, multiple
sclerosis, post-menopausal osteoporosis, non-structural scoliosis, hypertension
and chronic neck pain. Nineteen papers found Pilates to be more effective than
the control or comparator group at improving outcomes including pain and
disability levels. When assessed using the CONSORT and PEDro scales, the quality
of the papers varied, with more falling toward the upper end of the scale.
CONCLUSION: The majority of the clinical trials in the last five years into the
use of Pilates as a rehabilitation tool have found it to be effective in
achieving desired outcomes, particularly in the area of reducing pain and
disability. It indicates the need for further research in these many areas, and
especially into the benefits of particular Pilates exercises in the
rehabilitation of specific conditions.
PMID- 29332747
TI - Effects of spinal manipulation and myofascial techniques on heart rate
variability: A systematic review.
AB - BACKGROUND: The analysis of heart rate variability is important to the
investigation of stimuli from the autonomic nervous system. Osteopathy is a form
of treatment that can influence this system in healthy individuals as well as
those with a disorder or disease. OBJECTIVES: The aim of the present study was to
perform a systematic review of the literature regarding the effect of spinal
manipulation and myofascial techniques on heart rate variability. METHODS:
Searches were performed of the Pubmed, Scielo, Lilacs, PEDro, Ibesco, Cochrane
and Scopus databases for relevant studies. The PEDro scale was used to assess the
methodological quality of each study selected. RESULTS: A total of 505 articles
were retrieved during the initial search. After an analysis of the abstracts,
nine studies were selected for the present review. CONCLUSION: Based on the
findings, osteopathy exerts an influence on the autonomic nervous system
depending on the stimulation site and type. A greater parasympathetic response
was found when stimulation was performed in the cervical and lumbar regions,
whereas a greater sympathetic response was found when stimulation was performed
in the thoracic region.
PMID- 29332748
TI - The Pilates client on the hypermobility spectrum.
PMID- 29332749
TI - Long-term effect of direction-movement control training on female patients with
chronic neck pain.
AB - BACKGROUND: Treatment of movement faults in the neck is known as an important
factor in treatment of chronic neck pain. Along with the identification of site
and direction of the faults, direction-movement control intervention retrains the
control of the movement faults. PURPOSE: This study was designed to investigate
long-term effects of a direction-movement control training on pain, disability,
head repositioning accuracy, function, cervical flexor endurance, and range of
motion in female patients with chronic nonspecific neck pain. MATERIAL AND
METHODS: Thirty women (36.5 +/- 5.7 years) with chronic nonspecific neck pain
were randomly allocated into two groups, i.e., an experimental group (n = 15) and
a control group (n = 15). The experimental group performed the direction-movement
control training for 30 min/day, three days per week for six months. All subjects
were evaluated using the visual analog scale (VAS), range of motion (TOM),
progressive iso-inertial lifting evaluation (PILE), neck disability Index (NDI),
helmet attached with laser pointer using for head repositioning accuracy (HRA),
and Trott's test (deep neck flexor endurance), in pre- and six-months post
treatment intervention. RESULTS: Significant differences were observed for the
pain, neck disability Index, function endurance, head repositioning accuracy,
range of motion, and cervical flexor endurance in the experimental group compared
to that of control group. CONCLUSION: Direction-movement control training is
likely to be an effective training program to enhance body functionality through
improvement of pain, function, endurance, head repositioning accuracy, range of
motion, and cervical flexor endurance. Due to the high reported effect size for
direction-movement control exercises, the application of the training is
suggested as a supplementary method to improve chronic nonspecific neck pain in
females.
PMID- 29332750
TI - The influence of surface angle on muscle activity during Pilates based exercises.
PMID- 29332751
TI - Gamification.
PMID- 29332752
TI - The effects of neck mobilization in patients with chronic neck pain: A randomized
controlled trial.
AB - OBJECTIVE: To determine the effect of mobilization and routine physiotherapy on
pain, disability, neck range of motion (ROM) and neck muscle endurance (NME) in
patients having chronic mechanical neck pain (NP). METHODS: Sixty eight patients
with chronic mechanical NP were randomly allocated into two groups by using a
computer generated random sequence table with 34 patients in the multi-modal
mobilization group and 34 patients in the routine physiotherapy group. Baseline
values for pain, disability, NME, and neck ROM were recorded using visual
analogue scale (VAS), neck disability index (NDI), neck flexor muscle endurance
test and universal goniometer respectively, before the treatment. Each patient
received 10 treatment sessions over a period of four weeks and at the end of four
weeks all the outcome measures were recorded again. RESULTS: A paired t-test
revealed significant pre to post treatment differences for all outcome measures
in both groups (p <= 0.001 in all instances). An independent t-test revealed
statistically significant differences for pain, disability, NME, and neck ROM in
favor of the multi-modal mobilization group with a between group difference of
1.57 cm for VAS (p < 0.001), 11.74 points for NDI (p = 0.001), 18.45 s for NME (p
< 0.001) and 6.06-8.24 degrees for neck ROM (p < 0.05). CONCLUSION: The results
suggest that a combination of cervical mobilization with routine physiotherapy is
more effective for reducing pain and disability and improving NME and neck ROM in
patients with chronic mechanical NP compared to routine physiotherapy alone.
PMID- 29332753
TI - Cognitive Functional Therapy (CFT) for chronic non-specific neck pain.
AB - This case report presents the effect of Cognitive Functional Therapy (CFT) in a
patient with chronic non-specific neck pain. The patient believed that pain
signified tissue damage, and demonstrated pain catastrophizing, hypervigilance,
stress sensitivity, and movement impairment of the neck, during extension and
rotation. The CFT intervention integrated a cognitive approach with manual
therapy and active exercises to encourage the patient to trust her neck again.
One month after the first appointment, the patient had recovered confidence, and
the pain and disability had disappeared almost entirely.
PMID- 29332754
TI - Conservative management of thumb carpometacarpal osteoarthritis: An Italian
survey of current clinical practice.
AB - OBJECTIVE: The purpose of this study was to elucidate expert opinion on the
conservative treatment of thumb carpometacarpal (CMC) joint osteoarthritis (OA).
METHODS: A 21-item survey to determine the practice patterns of Italian hand
therapists who treat arthritis of the CMC joint was developed and distributed
through a professional online survey service to assure confidentiality and
anonymity. RESULTS: Of the respondents, 80.8% were physical therapists; the
remaining 19.2% were occupational therapists. 84.6% of the specialists who make
decisions regarding patient pain management education. CONCLUSIONS: There is
variability in the knowledge and practice patterns of Italian hand therapists
relating to conservative management of thumb CMC OA.
PMID- 29332755
TI - Investigating the anticipatory postural adjustment phase of gait initiation in
different directions in chronic ankle instability patients.
AB - OBJECTIVE: The main objective of the present study was to analyze how supra
spinal motor control mechanisms are altered in different directions during
anticipatory postural phase of gait initiation in chronic ankle instability
patients. It seems that supra spinal pathways modulate anticipatory postural
adjustment phase of gait initiation. Yet, there is a dearth of research on the
effect of chronic ankle instability on the anticipatory postural adjustment phase
of gait initiation in different directions. METHOD: A total of 20 chronic ankle
instability participants and 20 healthy individuals initiated gait on a force
plate in forward, 30 degrees lateral, and 30 degrees medial directions.
RESULTS: According to the results of the present study, the peak lateral center
of pressure shift decreased in forward direction compared to that in other
directions in both groups. Also, it was found that the peak lateral center of
pressure shift and the vertical center of mass velocity decreased significantly
in chronic ankle instability patients, as compared with those of the healthy
individuals. CONCLUSION: According to the results of the present study, it seems
that chronic ankle instability patients modulate the anticipatory postural
adjustment phase of gait initiation, compared with healthy control group, in
order to maintain postural stability. These changes were observed in different
directions, too.
PMID- 29332756
TI - Asymmetry of activation of lateral abdominal muscles during the
neurodevelopmental traction technique.
AB - OBJECTIVE: The aim of the study was to evaluate the symmetry and pattern of
activation of lateral abdominal muscles (LAM) in response to neurodevelopmental
traction technique. DESIGN AND PARTICIPANTS: Measurements of LAM thickness were
performed in four experimental conditions: during traction with the force of 5%
body weight (5% traction): 1) in neutral position, 2) in 20 degrees posterior
trunk inclination; during traction with the force of 15% body weight (15%
traction): 3) in neutral position, 4) in 20 degrees posterior trunk inclination.
Thirty-seven healthy children participated in the study. INTERVENTIONS: Not
applicable. MAIN OUTCOME MEASURES: To evaluate LAM activation level ultrasound
technology was employed (two Mindray DP660 devices (Mindray, Shenzhen, China)
with 75L38EA linear probes). An experiment with repeated measurements of the
dependent variables was conducted. RESULTS: Side-to-side LAM activation asymmetry
showed relatively high magnitude, however, significant difference was found only
in case of the obliquus externus (OE) during stronger traction (P < 0.05). The
magnitude of LAM thickness change formed a gradient, with the most profound
transversus abdominis (TrA) showing the smallest change, and the most superficial
OE - the greatest. The inter-muscle differences were most pronounced between the
OE and TrA (P < 0.001). CONCLUSIONS: During the neurodevelopmental traction
technique there is a difference in individual LAM activation level, with deeper
muscles showing less intense activation. In statistical terms, the only signs of
side-to-side asymmetry of LAM activation are visible in case of the OE, however,
the magnitude of asymmetry is relatively high. The results allow to identify
patterns of activation of LAM in children showing typical development that will
serve as a reference in future studies in children with neurological disorder.
PMID- 29332757
TI - Activation of lower limb muscles with different types of mount in hippotherapy.
AB - OBJECTIVES: To analyze muscle activation of lower limbs (LL) of subjects in
hippotherapy sessions. METHODS: The study included 10 healthy subjects, five male
and five female, with an average age of 24.03 (+/-4.06) years. Subjects underwent
four hippotherapy sessions of 30 min with interval of one week, and each session
was performed with a different type of mount material in the following order: 1st
performed with saddle and feet in the stirrups (S1), 2nd with saddle and feet off
the stirrups (S2), 3rd with blanket and feet off the stirrup (S3) and 4th with
blanket and feet in the stirrups (S4). Surface electromyographies were performed
at 1, 10, 20 and 30 min of session, and the electrodes were placed on muscle
bellies bilaterally on the muscles rectus femoris, vastus medialis, vastus
lateralis and tibialis anterior. RESULTS: The analysis of muscle activity during
these four sessions showed a significant difference in muscle recruitment in LL,
and sessions with blanket and feet in the stirrups provided greater muscle
activation of quadriceps and tibialis anterior with the horse at step gait (p =
0.0002). CONCLUSION: The results suggest that feet positioned in the stirrups is
a relevant factor for greater muscle recruitment in LL to maintain postural
balance while riding, especially using a blanket as mount material for ride a
horse.
PMID- 29332758
TI - Prevalence of physical activity among adolescents in southern Brazil.
AB - OBJETIVE: The aim of this study was to estimate the prevalence of low physical
activity levels and to identify related factors (sociodemographic, lifestyle and
body weight status) in adolescents. METHODS: The study included 1103 students
aged 14-19 years from city of Sao Jose/SC, Brazil. Physical activity was assessed
using a questionnaire that classified adolescents into those who meet
recommendations and those who do not meet recommendations. Independent variables
were gender, age, monthly household income, maternal education, balanced diet,
number of physical education classes, sleep/day, tobacco use, excessive alcohol
use, screen time and weight status. Binary logistic regression was used to
estimate odds ratios and 95% confidence intervals. RESULTS: Prevalence of
inadequate levels of physical activity was 77.2%. Older students and those with
lower monthly family income were more likely to have inadequate levels of
physical activity. Female adolescents and older students were more likely to be
sufficiently active compared to male and younger adolescents. Adolescents who
sleep more hours/day were more likely to be insufficiently active. CONCLUSION:
Efforts to increase levels of physical activity should be focused on older
adolescents and those with lower monthly family income.
PMID- 29332759
TI - Neck pain in Iranian school teachers: Prevalence and risk factors.
AB - Neck pain (NP) is a common occupational health problem associated with a number
of professions. Many studies indicate that NP is common among teachers, yet no
published study was found to address the prevalence and risk factors of NP in
Iranian school teachers. The purpose of the current study was to assess the
prevalence and risk factors for NP among school teachers in Iran. A cross
sectional study was conducted on 586 randomly selected primary and high schools
teachers from 22 schools in Tehran, Iran. Point, last month, last 6 months,
annual, and lifetime prevalence rates of NP were 24%, 29%, 33%, 37%, and 43%,
respectively. There was a significant association and increased prevalence of NP
with a number of risk factors such as; being female, age, general health, length
of employment, regular exercise and job satisfaction (P < 0.05 in all instances).
Therefore, some individual and occupational factors may make conditions relevant
for the development of NP among teachers.
PMID- 29332760
TI - Ischemic compression and kinesiotherapy on chronic myofascial pain in breast
cancer survivors.
AB - OBJECTIVE: assess the effects of ischemic compression and kinesiotherapy on the
rehabilitation of breast cancer survivors with chronic myofascial pain. METHODS:
A randomized, controlled, blinded clinical trial was performed with 20 breast
cancer survivors with myofascial trigger point in the upper trapezius muscle.
Patients were randomly allocated to ischemic compression + kinesiotherapy (G1, n
= 10) and kinesiotherapy (G2, n = 10). Both groups were submitted to 10 sessions
of treatment. The variables evaluated were: Numeric Rating Scale, Pain Related
Self-Statement Scale, pressure pain threshold, Functional Assessment of Cancer
Therapy-Breast and Infrared thermography. RESULTS: A significant reduction (p <
0.05) was observed in pain intensity after 10 sessions in Groups 1 and 2, a
significant increase (p < 0.05) in pressure pain threshold in both the operated
and non-operated side after 10 sessions for Group 1. CONCLUSION: Ischemic
compression associated with kinesiotherapy increases the pressure pain threshold
on the myofascial trigger point in the upper trapezius muscle and reduces the
intensity of pain in breast cancer survivors with myofascial pain.
PMID- 29332761
TI - Exercise on balance and function for knee osteoarthritis: A randomized controlled
trial.
AB - OBJECTIVES: To assess balance and function of symptomatic and asymptomatic
subjects with knee osteoarthritis (OA) and investigate the influence of physical
exercise. DESIGN: Subjects were divided into three groups: Group 1 (n = 15),
symptomatic knee OA; Group 2 (n = 11), asymptomatic knee OA; and Group 3 (n =
16), knee OA and no intervention. History of falls, the WOMAC questionnaire,
balance and functionality were assessed. RESULTS: After intervention, there was a
significant difference in the total WOMAC score and in the pain and function
domains only in Group 1. After intervention, Group 2 showed significant
differences in decreased time on the Step Up/Over test and postural sway
increased. CONCLUSION: After the intervention, the symptomatic group reported
improvement in pain and function on the WOMAC, while the asymptomatic group
showed improvement in performance in the Step Up/Over test. There were no new
episodes of falls in groups 1 and 2.
PMID- 29332762
TI - The effect of foot orthoses on joint moment asymmetry in male children with
flexible flat feet.
AB - INTRODUCTION: It has been widely postulated that structural and functional
misalignments of the foot, such as flat foot, may cause mechanical deviations of
the lower limb during walking. The aim of this study was to investigate the
effect of foot orthoses on lower extremity joint moment asymmetry during the
stance phase of walking in children with asymptomatic flexible flat feet.
METHODS: Fourteen volunteer male children, clinically diagnosed with flexible
flat feet, participated in this study. Subjects completed 12 walking trials at a
self-selected walking speed while 3-dimensional kinematic and kinetic data were
collected for two conditions: shod with no orthoses, and shod with orthoses. The
gait asymmetry index for each variable for each subject was defined as: (1
(lesser moment/greater moment)) * 100. RESULTS: Results reveal no significant
differences in ankle or knee joint moment asymmetry. However, the use of foot
orthoses decreased asymmetry for the hip abduction moment (P = 0.04) compared to
walking without orthoses and also resulted in subtle, non-significant increases
in frontal plane subtalar and sagittal plane knee and hip joints moment
asymmetry. CONCLUSION: We conclude that foot orthoses decrease frontal plane hip
joint moment asymmetry, but have little effect on ankle and knee joint asymmetry.
PMID- 29332763
TI - Fascia - The unsung hero of spine biomechanics.
PMID- 29332764
TI - Pelvic musculoskeletal dysfunctions in women with and without chronic pelvic
pain.
AB - AIM: This study aimed to compare the prevalence of pelvic musculoskeletal
dysfunctions in women with and without Chronic Pelvic Pain (CPP). MATERIALS
&METHODS: A total of 84 women with and without CPP (42 in each group),
participated in this cross-sectional analytical study. After collecting
demographic information, clinical examinations were carried out to compare pelvic
musculoskeletal dysfunctions between two groups. Kolmogorov-Smirnov (K-S)
goodness-of-fit, Independent t, X2 and Pearson correlation tests were used for
data analysis. Values of p < 0.05 were considered statistically significant.
FINDINGS: Significant differences were found in the asymmetric iliac crest and
pubic symphysis height (45.2% vs 9.5%), positive sacroiliac provocation and
positive Carnett's tests (50% vs 4.8%), (p < 0.05). CPP Patients exhibited more
tenderness at Levator ani, Piriformis, and Obturator Internus muscles, also
higher degrees of pelvic inclination (p < 0.05). CONCLUSION: Higher frequency of
pelvic musculoskeletal dysfunctions in women with CPP suggests the value of
routine musculoskeletal examinations for earlier diagnosis of musculoskeletal
originated CPP and effective management of these patients.
PMID- 29332765
TI - Aquatic myofascial release applied after high intensity exercise increases
flexibility and decreases pain.
AB - OBJECTIVES: To investigate aquatic myofascial release (AMR) effects on
flexibility and delayed onset muscle soreness, after high intensity exercises.
STUDY DESIGN: 15 participants, control (CON) and intervention (INT), 3 moments,
pre (Pre), after (Post) and 50 min after (Post 50/Post AMR). 6 exercises, 5 sets,
15 reps at 85% of 1 maximum repetition, followed, or not, by 50 min of AMR.
VARIABLES: Heart rate, lactate, rate of perceived exertion, pain and flexibility.
RESULTS: Pain perception decreased in all moments (CON4.47 +/- 2.36; INT1.13 +/-
1.46, p = 0.0002). Flexibility only increased for the fingertip to floor test in
both phases in the Post50/Post AMR compared to Post (CON14.33 +/- 9.19Pre, 15.07
+/- 9.37Post (p = 0.7) and 12.8 +/- 4.69Post50 (p = 0.4); INT14.53 +/- 9.06Pre,
13.87 +/- 9.88Post (p = 0.2) and 11.03 +/- 8.96Post AMR (p = 0.001)). The Well's
bench improved only for the Post AMR compared to Pre in the INT phase (INT24.79
+/- 9.91Pre; 27.67 +/- 9.46Post AMR p = 0.0000023). CONCLUSION: We concluded that
AMR is effective to reduce pain perception and to improve flexibility of the
studied population submitted to a high intense exercise session.
PMID- 29332766
TI - Cognitive function in Rett syndrome: Profoundly impaired or near normal?
PMID- 29332768
TI - Will a Screwdriver Work?
PMID- 29332767
TI - Burn Care: Resuscitation and Respiratory Care.
PMID- 29332769
TI - Articles That May Change Your Practice: Hypertonic Fluid Resuscitation in Trauma.
PMID- 29332770
TI - Forum.
PMID- 29332771
TI - 26th Critical Care Transport Medicine Conference.
PMID- 29332772
TI - 2017 Community Awards.
PMID- 29332773
TI - Does Medical Staffing Influence Perceived Safety? An International Survey on
Medical Crew Models in Helicopter Emergency Medical Services.
AB - OBJECTIVE: The competence, composition, and number of crewmembers have generally
been considered to influence the degree of patient care and safety in helicopter
emergency medical services (HEMS), but evidence to support the advantages of one
crew concept over another is ambiguous; additionally, the benefit of physicians
as crewmembers is still highly debated. METHODS: To compare perceived safety in
different medical crew models, we surveyed international HEMS medical directors
regarding the types of crew compositions their system currently used and their
supportive rationales and to evaluate patient and flight safety within their
services. RESULTS: Perceived patient and flight safety is higher when HEMS is
staffed with a dual medical crew in the cabin. Tradition and scientific evidence
are the most common reasons for the choice of medical crew. Most respondents
would rather retain their current crew configuration, but some would prefer to
add a physician or supplement the physician with an assistant in the cabin.
CONCLUSION: Our survey shows a wide variety of medical staffing models in HEMS
and indicates that these differences are mainly related to medical competencies
and the availability of an assistant in the medical cabin. The responses suggest
that differences in medical staffing influence perceived flight and patient
safety.
PMID- 29332775
TI - Development and Testing of a Neonatal Intubation Checklist for an Air Medical
Transport Team.
AB - OBJECTIVE: We developed a Neonatal Intubation Checklist for Airlift Northwest.
Our goal was to improve the preparation, technical proficiency, and safety of
neonatal intubation without increasing the time required to perform the
procedure. METHODS: The Neonatal Intubation Checklist, a "call and response"
checklist for neonatal intubation, was developed. Its effectiveness was evaluated
during a baseline assessment and 2 practice sessions after a checklist
orientation. Intubation proficiency was evaluated using a validated assessment
tool that included a proficiency score, a global rating scale (GRS) score, and
time to perform the procedure. RESULTS: Significant improvements in intubation
proficiency and time to intubation were noted when teams used the intubation
checklist (proficiency score: 29 [7] at baseline vs. 57 [1] with checklist, P <
.001; GRS 2 [2, 2.5] at baseline vs. 5 [3, 5] with checklist, P < .001; baseline
intubation time 626 [93] seconds vs. 479 (44) seconds with checklist, P < .001).
These changes were associated with a large effect on proficiency (n2 = 0.89), GRS
(n2 = 0.6), and time to successful intubation (n2 = 0.52). CONCLUSION: The use of
the Neonatal Intubation Checklist improved transport team performance during
simulated neonatal intubations and decreased the time required to successfully
perform the procedure.
PMID- 29332774
TI - An Analysis of Intoxicated Patients Transported by a Doctor Helicopter.
AB - OBJECTIVE: We retrospectively investigated all of the intoxicated patients who
were transported by a doctor helicopter (DH) in eastern Shizuoka between April
2004 and December 2015 to determine when air medical transport was used in cases
of toxic exposure. METHODS: Subjects were divided into 2 groups: an outpatient
group of subjects who went home after receiving a medical evaluation and
treatment and an admission group. RESULTS: The outpatient and admission groups
included 17 and 31 subjects, respectively. The ratio of dispatching the DH to the
scene and the median Glasgow Coma Scale score in the outpatient group were
greater, and the shock index in the outpatient group was significantly smaller
than in the admission group. The duration from exposure of intoxicated agents to
contact by staffs of the DH in the outpatient group was also smaller than in the
admission group. CONCLUSION: The level of consciousness and shock index may be
important factors dictating whether or not to dispatch the DH in order to prevent
secondary damage induced by unstable circulation.
PMID- 29332776
TI - Compliance With a National Standard by Norwegian Helicopter Emergency Physicians.
AB - OBJECTIVE: The "National Standard Requirements for Helicopter Emergency Medicine
Services Physicians" gives recommendations on medical requirements for flight
physicians. This study describes the level of formal competence, experience, and
guideline compliance of Norwegian helicopter emergency medical service (HEMS)
physicians. METHODS: In May 2013, all HEMS physicians with full-time engagement
at Norwegian HEMS bases were invited to participate in a cross-sectional survey
using a structured, Web-based questionnaire. RESULTS: A total of 108 (79%) of 136
physicians replied to the survey, and all bases were represented. The majority
(89%) had specialist training, and more than 60% had longer than 6 years of
experience as a flight physician. Over 60% had attended trauma, pediatric, and
incubator courses, and all physicians worked regularly in an anesthesia
department. Most physicians were participating in simulation and procedure
training. CONCLUSION: Many of the basic requirements of the guidelines were met
by HEMS physicians, but room exists for improvements. Norwegian HEMS physicians
are experienced, but a need exists for a more structured curriculum in emergency
medicine for HEMS physicians based on the broad spectrum of presented medical
conditions to ensure optimal quality of care and safety for all patients in
Norway.
PMID- 29332777
TI - Means for Transport in Patients After Remote Extracorporeal Membrane Oxygenation
Implantation.
PMID- 29332778
TI - Cricothyrotomy in Helicopter Emergency Medical Service Transport.
AB - OBJECTIVE: Airway management is a requisite skill set for helicopter emergency
medical service (HEMS) providers. Cricothyrotomy is a potentially lifesaving
skill that is used when other airway maneuvers fail. The authors reviewed all
transports by a helicopter program in which cricothyrotomy was performed to
assess the frequency, success, and technique. METHODS: This was a retrospective
chart review of air medical patient records from an electronic medical record
system over a 112-month period. RESULTS: During the study period, 22,434 patients
were transported, 13 (.057%) of whom underwent cricothyrotomy. The typical
patient was a male trauma victim with a mean Glasgow Coma Score of 5 transported
from an accident scene with a mean age of 34.3 years. Six (46%) of the patients
were alive at 24 hours. All patients (13/100%) received attempted endotracheal
intubation; the mean number of attempts per patient was 2. The success rate was
100% with all patients ventilated via cricothyrotomy. CONCLUSION: This study
shows cricothyrotomy is a rarely performed skill but that HEMS providers are able
to successfully learn the skill with proper training and oversight.
PMID- 29332779
TI - Helicopter Emergency Medical Services Literature 2014 to 2016: Lessons and
Perspectives, Part 1-Helicopter Transport for Trauma.
PMID- 29332780
TI - Social Media and Integrity.
PMID- 29332781
TI - Pediatric Extracorporeal Cardiopulmonary Resuscitation Patient With Traumatic
Subarachnoid Hemorrhage and Takotsubo Syndrome.
AB - Takotsubo syndrome is rare in pediatric patients but must be considered in
patients with subarachnoid hemorrhage with pulmonary edema and cardiomyopathy. A
systematic, collaborative approach is needed to facilitate emergent transfer of
patients where extracorporeal cardiopulmonary resuscitation (e-CPR) is used as a
lifesaving measure. Extracorporeal membrane oxygenation (ECMO) use in transport
requires preplanning, role delineation, resources, and research efforts to be
successful. We present an unusual transport case of successful e-CPR/ECMO
treatment of Takotsubo syndrome in a 12-year-old boy with an isolated traumatic
intracranial injury, cardiomyopathy with pulmonary edema, and multiple cardiac
arrests.
PMID- 29332782
TI - Long-Distance, Nonstop Neonatal Transport From Shanghai, China, to Genoa, Italy.
AB - The purpose of this article is to describe the long-distance, nonstop
intercontinental transport of a severely ill, mechanically ventilated newborn
from Shanghai, China, to Genoa, Italy focusing in particular on the clinical and
planning difficulties. The aircraft equipment, the assessment and preparation for
transport are discussed.
PMID- 29332783
TI - Out-of-Hospital Lateral Canthotomy and Cantholysis: A Case Series and Screening
Tool for Identification of Orbital Compartment Syndrome.
PMID- 29332784
TI - Air Transport of a Patient With Impending Cerebral Herniation From Tension
Pneumocephalus.
AB - Tension pneumocephalus is a rare but dangerous complication of craniotomy, sinus
surgery, and traumatic cranial injury. Compared with simple pneumocephalus, which
often resolves spontaneously over the course of a few days, tension
pneumocephalus tends to increase with ongoing cerebrospinal fluid leak and
requires immediate neurosurgical treatment to prevent cerebral herniation. Air
transport of patients with tension pneumocephalus for neurosurgical care entails
a risk of neurologic worsening because of changes in ambient air pressure with
altitude and cabin pressurization. We describe a case in which severe symptomatic
tension pneumocephalus developed after endoscopic endonasal sinus surgery in an
81-year-old man. The patient lived in a remote area and required air transport
for medical care. Pretreatment with oxygen therapy and maintaining the patient in
a flat supine position rapidly improved his neurologic status, allowing
transportation without incidence. A recommendation was also made to the medical
transport team to fly at the lowest possible altitude. Specific precautions may
enable safe transport of these critically ill patients for treatment, although
further data must be obtained before these can be definitively recommended.
PMID- 29332785
TI - The "Squeeze," an Interesting Case of Mask Barotrauma.
PMID- 29332786
TI - Recent advances and developments on integrating nanotechnology with
chemiluminescence assays.
AB - Chemiluminescence (CL) techniques are extensively utilized for detection of
analytes due to their high sensitivity, rapidity and selectivity. With the advent
of nanotechnology and incorporation of the nanoparticles in the CL system has
revolutionized the assays due to their unique optical and mechanical properties.
Several CL-based reactions have been developed where these nanoparticle based CL
sensors have evolved as excellent prospects for sensing in various analytical
applications. This review article addresses the nanoparticles based CL detection
system that are recently developed, the mechanisms has been summarized and the
role of luminophors have been discussed. This article critically analyzes the
optimal conditions for the CL detection along with quantitative assessment of the
analytes. We have included the use of semiconductor nanoparticles, metal
nanoparticles, graphene based nanostructures, mesoporous nanospheres, layered
double hydroxides, clays for CL detection. The scope and application of these
nanoscale material based CL system in various branches of science and technology
including chemistry, biomedical applications, pharmaceutics, food, environmental
and toxicological applications has been critically summarized.
PMID- 29332787
TI - Rapid and interference-free analysis of nine B-group vitamins in energy drinks
using trilinear component modeling of liquid chromatography-mass spectrometry
data.
AB - The aim of the present work was to develop a rapid and interference-free method
based on liquid chromatography-mass spectrometry (LC-MS) for the simultaneous
determination of nine B-group vitamins in various energy drinks. A smart and
green strategy that modeled the three-way data array of LC-MS with second-order
calibration methods based on alternating trilinear decomposition (ATLD) and
alternating penalty trilinear decomposition (APTLD) algorithms was developed. By
virtue of "mathematical separation" and "second-order advantage", the proposed
strategy successfully solved the co-eluted peaks and unknown interferents in LC
MS analysis with the elution time less than 4.5min and simple sample preparation.
Satisfactory quantitative results were obtained by the ATLD-LC-MS and APTLD-LC-MS
methods for the spiked recovery assays, with the average spiked recoveries
ranging from 87.2-113.9% to 92.0-111.7%, respectively. These results acquired
from the proposed methods were confirmed by the LC-MS/MS method, which shows a
quite good consistency with each other. All these results demonstrated that the
developed chemometrics-assisted LC-MS strategy had advantages of being rapid,
green, accurate and low-cost, and it could be an attractive alternative for the
determination of multiple vitamins in complex food matrices, which required no
laborious sample preparation, tedious condition optimization or more
sophisticated instrumentations.
PMID- 29332788
TI - Turn-on fluorescent sensor for the detection of glucose using manganese dioxide
phenol formaldehyde resin nanocomposite.
AB - Monitoring blood glucose has attracted considerable attention because diabetes
mellitus is a global public health problem. Herein, we reported a turn-on
fluorescence detection strategy based on manganese dioxide (MnO2)-phenol
formaldehyde resin (PFR) nanocomposite for rapid, sensitive, and selective
detection of glucose levels in human blood. In this biosensing system, MnO2
nanoshell on the PFR nanoparticle surfaces serve as a quencher. PFR fluorescence
can make a recovery in the presence of H2O2, reducing MnO2 to Mn2+. The sensor
shows a linear range from 50nM to 90MUM with a low detection limit of 20nM for
H2O2 detection. Thus, the glucose can be detected on the basis of the enzymatic
conversion of glucose by glucose oxidase to produce H2O2. This method exhibits a
wide linear range from 5MUM to 1mM with a low detection limit of 1.5MUM. Because
of the excellent photostability offered by PFR, the developed strategy has been
successfully applied for the diagnosis of diabetes mellitus in human blood
samples. Compared with commercial glucometer, our method showed satisfactory
results, indicating the significant reliability. The developed turn-on
fluorescent sensor might hold great promise in nanomedicine and bioanalysis.
PMID- 29332789
TI - Mn2+-doped NaYF4:Yb,Er upconversion nanoparticles for detection of uric acid
based on the Fenton reaction.
AB - A novel fluorescence method for the determination of hydrogen peroxide (H2O2) and
uric acid (UA) was developed. The procedure was based on the hydroxyl radicals
(.OH), which effectively quenched the fluorescence of the Mn2+-doped NaYF4:Yb,Er
upconversion nanoparticles (UCNPs). Based on the property of Mn2+-doped
NaYF4:Yb,Er upconversion nanoparticles, the Fenton reaction and enzymatic
reaction of uric acid, this method could be used for highly sensitive detection
of H2O2 and uric acid. Under optimal conditions, we observed that the
fluorescence quenching signal showed good linearity with the H2O2 concentration
in the range of 3.00*10-8 M ~ 6.00*10-5 M, and the detection limit of this assay
was 1.30*10-8 M. Meanwhile, the linear concentration range for UA was 4.00*10-9 M
~ 1.00*10-5 M, and the lower limit of detection was 1.90*10-9 M. Furthermore, the
developed method was successfully used for the determination of UA levels in
human serum with satisfactory results.
PMID- 29332790
TI - Ultrasensitive electrochemical detection of poly (ADP-ribose) polymerase-1 via
polyaniline deposition.
AB - Recent findings have thrust poly ADP (ADP: adenosine diphosphate)-ribose
polymerase-1 (PARP-1) into the limelight as potential chemotherapeutic target
because it is closely related to the development of tumor. So, studies on its
detection and inhibitors evaluation have attracted more attention. It is
interesting that poly (ADP-ribose) (PAR), the catalytic product of PARP-1 in the
existence of nicotinamide adenine dinucleotide (NAD+), possess twice charge
density of DNA strands. PAR contain 200 units, i.e., about 400bp bases, and
multiple branched strands. So, plentiful negative charges on PAR supplied
exquisite environment for PANI deposition, which was triggered by horseradish
peroxidase (HRP). Because of the unique electrochemical property of PANI,
ultrasensitive electrochemical detection of PARP-1 was proposed. Under optimum
conditions, DPV intensity linearly increased with the increment of PARP-1 in the
range of 0.005-1.0 U. The detection limit was 0.002 U, which was comparable or
more sensitive than that obtained from previously reported strategies.
PMID- 29332791
TI - Highly sensitive and reproducible non-enzymatic glucose sensor fabricated by drop
casting novel nanocomposite with 3D architecture and tailorable properties
prepared in controllable way.
AB - Novel nanocomposite has tailorable properties and ordered 3D architecture similar
to the structure of materials prepared by electrodeposition which is convenient
and efficient but the reproducibility is limited because of the uncontrollable
preparation process, was scientifically synthetized in controllable way and used
for non-enzymatic glucose sensor for the first time. Flower-like alpha-Ni(OH)2
with high specific surface areas and good anion transport ability benefited from
its distinctive stacking faults and turbostratic disorder structure was
synthesized through facile one-step hydrothermal method. Oversaturated gold
nanoparticles (AuNPs) have been innovatively decorated on flower-like alpha
Ni(OH)2 to improve the electrical conductivity, in turn, AuNPs would possess the
higher catalytic activity when supported on Ni(OH)2, so the resultant AuNPs
decorated alpha-Ni(OH)2 (AuNPs@alpha-Ni(OH)2) also has excellent synergistic
catalytic effect and improved selectivity. On this basis, beta-cyclodextrins
functionalized reduced graphene oxide (beta-rGO) with enhanced dispersivity was
scientifically added at optimized proportion to reduce the interparticle
resistance of AuNPs@alpha-Ni(OH)2 as 2D electron transport channels, and to
improve film-forming ability of the obtained nanocomposite via forming stable 3D
network structure. Non-enzymatic glucose sensor fabricated through drop-casting
the prepared nanocomposite on glass carbon electrode has high sensitivity up to
559.314MUAmM-1cm-2 over the low concentration range and 327.199MUAmM-1cm-2 over
the higher concentration range, comparable to the sensors modified by
electrodeposition method, indicating that prepared nanocomposite with controlling
nanoscale composition and architectures based on rational design is an effective
strategy to construct electrochemical sensor with excellent performance.
PMID- 29332792
TI - Silver ions enhanced AuNCs fluorescence as a turn-off nanoprobe for
ultrasensitive detection of iodide.
AB - Fluorescence nanoprobes are frequently employed to construct sensitive biosensors
via turn-on and turn-off strategy. In this paper, a novel strategy for
ultrasensitive detection of iodide was firstly constructed based on Ag+ regulated
photoluminescence enhancement of gold nanoclusters (AuNCs) as a turn-off
nanoplatform. In the presence of Ag+, the fluorescence (FL) intensity of AuNCs
can be enhanced obviously. When adding iodide ions (I-) in the Ag+-AuNCs, Ag+ can
be pulled down from AuNCs and results in quenching of the fluorescent effectively
owing to the combination between Ag+ and I-. Compared with that of I- directly
reaction with AuNCs, the introducing of Ag+ shows improved quenching efficiency
from 32% to 66% since I- can react with Ag+ as well as AuNCs. Therefore, the
platform could be applied to assay Ag+ and I-, on the basis of the FL enhancement
and the further FL quenching. The detection ranges and detection limits were 0.2
12MUM and 0.06MUM for Ag+, 0.001-6MUM and 0.3nM for I-, respectively. The new
sensing method based on ion regulation to enhance the detection sensitivity can
extend to the appliance of other fluorescent materials in biosensing and
biomedical field.
PMID- 29332793
TI - Label-free detection of histone based on cationic conjugated polymer-mediated
fluorescence resonance energy transfer.
AB - A simple and homogeneous histone assay is developed based on histone-induced DNA
compressing coupled with cationic conjugated polymer (CCP)-mediated fluorescence
resonance energy transfer (FRET). In this strategy, the CCP serves as the FRET
donor and SYBR Green I (SG), which can strongly fluoresce not at its free state
but after intercalated into the double stranded calf thymus DNA (dsDNA), serves
as the acceptor of FRET. In the absence of histone, the dsDNA-SG and CCP combine
with each other through electrostatic interaction and the strong FRET from CCP to
SG occurs due to the overlapping between the fluorescent emitting spectrum of the
CCP and the absorption spectrum of SG. Upon the introduction of histone, the
formed compact complex of histone/dsDNA will lead to the compression of dsDNA
structure and prevent SG binding to dsDNA and fluorescing, which gives rise to a
significant decrease of FRET efficiency between CCP and SG. Thus, the
quantitative analysis of histone is realized by monitoring the change of FRET
ratio, namely, the intensity ratio of the two emission bands of CCP and SG. Due
to the light harvesting and fluorescence amplification properties of CCP, high
sensitivity is achieved with a low detection limit of 0.74ng/mL histone. This
strategy provides a simple, homogeneous and sensitive strategy for histone
analysis in the study of histone-related biological processes.
PMID- 29332794
TI - A sensitive SPR biosensor based on hollow gold nanospheres and improved sandwich
assay with PDA-Ag@Fe3O4/rGO.
AB - A novel surface plasmon resonance (SPR) biosensor based on hollow gold
nanospheres (HGNPs) and an improved sandwich assay was developed to detect rabbit
IgG. The electromagnetic coupling between the HGNPs and Au film, and the notable
plasmonic fields spread over the inner and outer surfaces of HGNPs, led to the
considerable amplification of the SPR signal. Polydopamine-Ag@Fe3O4/reduced
graphene oxide (PDA-Ag@Fe3O4/rGO) was introduced to bind detection antibody (Ab2)
to form the improved sandwich structure. Ag nanoparticles were excited to produce
SPR and their hot electrons were doped on graphene thin films, which amplified
the response of biomolecules. Magnetic nanoparticles (Fe3O4) simplified the
collection of Ab2-PDA-Ag@Fe3O4/rGO. An external layer of polydopamine (PDA)
permitted the efficient immobilization of Ab2 without activation via abundant
functional groups and protected the nanoparticles from etching or agglomeration.
In addition, because of its large mass, Ab2-PDA-Ag@Fe3O4/rGO also played a key
role in the further amplification of the SPR response signals. This novel SPR
biosensor exhibited an effective response to the rabbit IgG at the different
concentrations ranging from 0.019 to 40.00MUgmL-1. This value is 132 times lower
than that observed for a traditional SPR biosensor based on Au-3
mercaptopropionic acid and 8 times lower than that obtained from an Ab2 sandwich
assay, which indicates that the SPR sensor has high sensitivity. In addition, the
designed biosensor showed satisfactory recoveries to detect the rabbit IgG spiked
in serum samples. Therefore, the novel SPR biosensor with high sensitivity and
acceptable recovery has potential for practical applications.
PMID- 29332795
TI - Polymer-based materials modified with magnetite nanoparticles for enrichment of
phospholipids.
AB - A polymeric material modified with magnetic nanoparticles (MNPs) has been
synthesized and evaluated as sorbent both for solid-phase extraction (SPE) and
dispersive magnetic solid-phase extraction (MSPE) of phospholipids (PLs) in human
milk samples. The synthesized sorbent was characterized by scanning electron
microscopy and its iron content was also determined. Several experimental
variables that affect the extraction performance (e.g. loading solvent,
breakthrough volume and loading capacity) were investigated and a comparison
between conventional SPE and MSPE modalities was done. The proposed method was
satisfactorily applied to the analysis of PLs in human milk fat extracts in
different lactation stages and the extracted PLs were determined by means of
hydrophilic interaction liquid chromatography using evaporative light scattering
detection.
PMID- 29332796
TI - Direct olive oil analysis by mass spectrometry: A comparison of different ambient
ionization methods.
AB - Analytical methods based on ambient ionization mass spectrometry (AIMS) combine
the classic outstanding performance of mass spectrometry in terms of sensitivity
and selectivity along with convenient features related to the lack of sample
workup required. In this work, the performance of different mass spectrometry
based methods has been assessed for the direct analyses of virgin olive oil for
quality purposes. Two sets of experiments have been setup: (1) direct analysis of
untreated olive oil using AIMS methods such as Low-Temperature Plasma Mass
Spectrometry (LTP-MS) or paper spray mass spectrometry (PS-MS); or alternatively
(2) the use of atmospheric pressure ionization (API) mass spectrometry by direct
infusion of a diluted sample through either atmospheric pressure chemical
ionization (APCI) or electrospray (ESI) ionization sources. The second strategy
involved a minimum sample work-up consisting of a simple olive oil dilution (from
1:10 to 1:1000) with appropriate solvents, which originated critical carry over
effects in ESI, making unreliable its use in routine; thus, ESI required the use
of a liquid-liquid extraction to shift the measurement towards a specific part of
the composition of the edible oil (i.e. polyphenol rich fraction or lipid/fatty
acid profile). On the other hand, LTP-MS enabled direct undiluted mass analysis
of olive oil. The use of PS-MS provided additional advantages such as an extended
ionization coverage/molecular weight range (compared to LTP-MS) and the
possibility to increase the ionization efficiency towards nonpolar compounds such
as squalene through the formation of Ag+ adducts with carbon-carbon double
bounds, an attractive feature to discriminate between oils with different degree
of unsaturation.
PMID- 29332797
TI - Electrodialytic in-line preconcentration for ionic solute analysis.
AB - Preconcentration is an effective way to improve analytical sensitivity. Many
types of methods are used for enrichment of ionic solute analytes. However,
current methods are batchwise and include procedures such as trapping and
elution. In this manuscript, we propose in-line electrodialytic enrichment of
ionic solutes. The method can enrich ionic solutes within seconds by quantitative
transfer of analytes from the sample solution to the acceptor solution under an
electric field. Because of quantitative ion transfer, the enrichment factor (the
ratio of the concentration in the sample and to that in the obtained acceptor
solution) only depends on the flow rate ratio of the sample solution to the
acceptor solution. The ratios of the concentrations and flow rates are equal for
ratios up to 70, 20, and 70 for the tested ionic solutes of inorganic cations,
inorganic anions, and heavy metal ions, respectively. The sensitivity of ionic
solute determinations is also improved based on the enrichment factor. The method
can also simultaneously achieve matrix isolation and enrichment. The method was
successively applied to determine the concentrations of trace amounts of
chloroacetic acids in tap water. The regulated concentration levels cannot be
determined by conventional high-performance liquid chromatography with
ultraviolet detection (HPLC-UV) without enrichment. However, enrichment with the
present method is effective for determination of tap water quality by improving
the limits of detection of HPLC-UV. The standard addition test with real tap
water samples shows good recoveries (94.9-109.6%).
PMID- 29332798
TI - Supported carbon dots serve as high-performance adsorbent for the retention of
trace cadmium.
AB - Carbon dots were prepared via a one-pot hydrothermal route, and a new solid-phase
extraction (SPE) adsorbent was developed by immobilizing the carbon dots on the
microcarrier cytopore, shortly termed as C-dots@cytopore. The C-dots@cytopore
composites were characterized by means of FT-IR, SEM, XPS and fluorescence
spectrometry. The performance of the composites for the adsorption of heavy
metals was thoroughly evaluated by using cadmium as a model. The binding of
cadmium on C-dots@cytopore fits Langmuir adsorption, and the adsorption dynamic
follows pseudo-second-order adsorption kinetics model. The binding of cadmium was
pH-dependent, with a maximum adsorption capacity of 2420MUgg-1 obtained at pH 4
7. A novel separation and preconcentration procedure was thus developed for trace
cadmium using the C-dots@cytopore composites as SPE sorbent. The retained cadmium
could be readily eluted and recovered by a 0.1molL-1 HNO3 solution and further
quantified with graphite furnace atomic absorption spectrometry (GFAAS). With a
sample volume of 1.0mL, an enrichment factor of 17.85 was obtained with a
detection limit of 1.8ngL-1 and a RSD value of 2.6% at 0.1MUgL-1 (n = 9). The
procedure was further validated by analyzing cadmium in certified reference
materials and a series of environmental water samples.
PMID- 29332800
TI - Acidity of substituted cathinones studied by capillary electrophoresis using the
standard and fast alternative approaches.
AB - Cathinone derivatives are notorious but still weakly characterized molecules,
known mainly as components of the designer and illicit drugs. The knowledge on
their acidity is scarce and incomplete, therefore, we decided to determine the
pKa values for six of them: 2-methylmethcathinone, 3-methylmethcathinone, 4
methylmethcathinone, alpha-pyrrolidinovalerophenone, methylenedioxypyrovalerone
and ephedrone. For that purpose we employed capillary electrophoresis, which is
known for its accurateness in comparison to other analytical techniques. We used
and compared two methodologically different approaches. The standard method
relied on measuring electrophoretic mobility across the broad pH range and
fitting the sigmoidal function. The obtained pKa values were in the range 8.59
9.10, thus these molecules remain mostly protonated and positively ionized in the
physiological conditions. The alternative two-values (TVM) and one-value methods
(OVM), proposed by us previously, have been used herein for the first time to the
cationic molecules. TVM enables estimation of pKa using only two electrophoretic
mobility values, referring to the total and partial ionization. OVM requires only
a single measurement because mobility of ion is predicted theoretically. Both TVM
and OVM yielded only a small deviation of pKa from the standard approach,
averagely 0.07-0.09pH unit. Two important issues have also been addressed: the
potential of a maximally fast calculation method using no repetition at the given
pH, and the accuracy of method with regard to pH attributed to partial
ionization. As a whole, the analytical potential of the TVM/OVM approach seems to
be huge and invaluable for fast pKa screening/estimation.
PMID- 29332799
TI - Rapid identification of regulated organic chemical compounds in toys using
ambient ionization and a miniature mass spectrometry system.
AB - Rapid, on-site analysis was achieved through significantly simplified operation
procedures for a wide variety of toy samples (crayon, temporary tattoo sticker,
finger paint, modeling clay, and bubble solution) using a miniature mass
spectrometry system with ambient ionization capability. The labor-intensive
analytical protocols involving sample workup and chemical separation,
traditionally required for MS-based analysis, were replaced by direct sampling
analysis using ambient ionization methods. A Mini beta ion trap miniature mass
spectrometer was coupled with versatile ambient ionization methods, e.g. paper
spray, extraction spray and slug-flow microextraction nanoESI for direct
identification of prohibited colorants, carcinogenic primary aromatic amines,
allergenic fragrances, preservatives and plasticizers from raw toy samples. The
use of paper substrates coated with Co3O4 nanoparticles allowed a great increase
in sensitivity for paper spray. Limits of detection as low as 5MUgkg-1 were
obtained for target analytes. The methods being developed based on the
integration of ambient ionization with miniature mass spectrometer represent
alternatives to current in-lab MS analysis operation, and would enable fast,
outside-the-lab screening of toy products to ensure children's safety and health.
PMID- 29332801
TI - A highly selective, colorimetric and ratiometric fluorescent probe for NH2NH2 and
its bioimaging.
AB - In this work, we report a novel approach which employed substrate-triggered
intramolecular addition-cyclization cascade to develop a highly selective
fluorescent probe E)-3-(4-(1H-phenanthro[9,10-d]imidazol-2-yl)phenyl)-1-(2
hydroxylphenyl) prop-2-en-1-one (P-OH) for NH2NH2. The new sensing mechanism of P
OH for NH2NH2 was investigated in detail by fluorescence spectroscopy, 1H NMR
titration, mass spectrometry and control experiments. The synthesized probe
showed ratiometric fluorescent response to NH2NH2 with naked-eye color changes
from yellow to colorless. It's noteworthy that this probe displayed high
sensitivity and selectivity to NH2NH2 over other species, including primary
amines, Cys, Hcy, GSH, HS- and HSO3-. Furthermore, the probe can not only detect
NH2NH2 in real water samples but also image NH2NH2 in living cells, indicating
its potential utility for NH2NH2 sensing in environmental and biological samples.
PMID- 29332802
TI - Total alpha1-acid glycoprotein determination in serum samples using disposable
screen-printed electrodes and osmium (VI) as electrochemical tag.
AB - Alpha-1-acid glycoprotein (AGP) or Orosomucoid is a serum glycoprotein which
belongs to the group of acute phase proteins. It is a potential biomarker for
inflammatory bowel diseases. In this sense, there is a need for developing fast
and cheap analytical methods for diagnosis, prognosis and follow-up of these
diseases. In this work, we propose a simple and cheap electrochemical method for
total AGP determination using disposable carbon screen-printed electrodes (SPE)
and using a selective acidic precipitation of the rest of proteins. This method
avoids the use of biological components, decreasing dramatically the analysis
cost. Firstly, AGP is labeled with an electrochemical tag (osmium (VI) complex)
and then the total amount of AGP is quantified by adsorptive transfer stripping
square wave voltammetry. The method optimized showed a good linear correlation (r
= 0.9992) and limit of detection of 1.6mgl-1. The methodology was successfully
applied to quantify AGP in a commercial serum sample. This methodology could be
useful in clinical diagnosis because of AGP levels increase two or three times
when inflammatory processes happen. Moreover, the inherent advantages of SPE
technology (low sample consumption, low cost and point of care testing) make this
methodology very attractive in this field.
PMID- 29332803
TI - Particle-based immobilized enzymatic reactors in microfluidic chips.
AB - The research and applications of immobilized enzyme reactors (IMERs) have become
more and more widespread due to the numerous advantages like reusability, easy
handling, prolonged lifetime, easy separation from products and substrate
specificity. The miniaturized form of these reactors (microchip IMERs) received
outstanding attention due to their special features and advantages over the
traditional, larger analytical systems. Large specific surface is essential for
the efficient operation of the microreactors, thus these devices include one of
the several types of porous solid supports, but in this work only the particle
based microchip IMERs are reviewed. A very large variety of micro- or
nanoparticles (beads) have been used in the microchip IMERs, however,
incorporating these particles into microchips is still a challenge, because the
common procedures used for the preparation of chromatographic columns are not
well applicable at the microscopic level. Many detection systems were applied
with microchip IMERs using on-chip or off-chip arrangement. The combination of
microchip IMERs with mass spectrometry is particularly popular, because in these
systems high-throughput analysis can be achieved by which the proteomic studies
can be largely accelerated. In most chip IMER-MS systems, the chips are used for
sample pretreatment including analyte (protein) digestion, preconcentration of
analyte, removal of matrix materials. Additional applications of the IMERs - like
the rapid protein digestion with proteolytic enzymes, the transformation of
analytes to a more easily or more sensitively measurable form (detection signal
amplification) and the design of microarrays/biosensors to analyze antigens based
on specific interactions in immunoanalytical studies - are also reviewed.
PMID- 29332804
TI - Effect of preprocessing high-resolution mass spectra on the pattern recognition
of Cannabis, hemp, and liquor.
AB - High-resolution mass spectrometry (HRMS) combined with pattern recognition was
used to discriminate among twenty-five Cannabis samples, twenty hemp samples, and
eight liquor samples. The effects of preprocessing on multivariate data analysis
were evaluated for Orbitrap high-resolution mass spectra. Different root
transformations were evaluated with respect to the bin width and the average
classification rates. In addition, linear binning and proportional binning with
various resolving powers were studied with respect to the average classification
rates. The proportional binning with the square root transformation gave the best
overall performance for chemical profiling or spectral fingerprinting. Six
classification methods, fuzzy rule-building expert system (FuRES), linear
discriminant analysis (LDA), super partial least squares discriminant analysis
(sPLS-DA), support vector machine (SVM), SVM classification tree type gap
(SVMTreeG), and SVM classification tree type entropy (SVMTreeH) had similar
trends in prediction rate with respect to the resolving power. The optimal
proportional mass bin width may depend on the data set, i.e., for the Cannabis
samples is resolving power 10-4, for the hemp samples and the liquor samples are
resolving power 10-3. Hence, data preprocessing methods such as different
transformations, binning strategies, and resolving powers are important factors
to be optimized for HRMS direct infusion measurements combined with pattern
recognition to be an authentication and characterization tool for various
products.
PMID- 29332805
TI - Trends of non-destructive analytical methods for identification of biodiesel
feedstock in diesel-biodiesel blend according to European Commission Directive
2012/0288/EC and detecting diesel-biodiesel blend adulteration: A brief review.
AB - Discrimination of biodiesel feedstock present in diesel-biodiesel blend is
challenging due to the great similarity in the spectral profile as well as
digital image profile of each type of feedstock employed in biodiesel production.
Once the marketed diesel-biodiesel blend is subsidized, in which motivates
adulteration in biofuel blend by cheaper supplies with high solubility to obtain
profits associated with the subsidies involved in biodiesel production. Non
destructive analytical methods based on qualitative and quantitative analysis for
detecting marketed diesel-biodiesel blend adulteration are reviewed. Therefore,
at the end is discussed the advantage of the qualitative analysis over
quantitative analysis, when the systems require immediate decisions such as to
know if the marketed diesel-biodiesel blend is unadulterated or adulterated in
order to aid the analyst in selecting the most appropriate green analytical
procedure for detecting diesel-biodiesel blend adulteration proceeding in fast
way. This critical review provides a brief review on the non-destructive
analytical methods reported in scientific literature based on different first
order multivariate calibration models coupled with spectroscopy data and digital
image data to identify the type of biodiesel feedstock present in diesel
biodiesel blend in order to meets the strategies adopted by European Commission
Directive 2012/0288/EC as well as to monitoring diesel-biodiesel adulteration.
According to that Directive, from 2020 biodiesel produced from first-generation
feedstock, that is, oils employed in human food such as sunflower, soybean,
rapeseed, palm oil, among other oils should not be subsidized. Therefore, those
non-destructive analytical methods here reviewed are helpful for discrimination
of biodiesel feedstock present in diesel-biodiesel blend according to European
Commission Directive 2012/0288/EC as well as for detecting diesel-biodiesel blend
adulteration.
PMID- 29332806
TI - Defects regulating of graphene ink for electrochemical determination of ascorbic
acid, dopamine and uric acid.
AB - A simple water immersing treatment has been established for regulating the
electrocatalytic activity of commercial graphene ink. This process enables to
remove additives in graphene ink and consequently expose the surface defects. A
graphene ink coated glass has been fabricated as an example platform for
simultaneous determination of ascorbic acid (AA), dopamine (DA), and uric acid
(UA). Cyclic voltammetry studied indicated electrocatalytic reaction can be
initiated after the additives leaching during the water immersing treatment.
Under optimal conditions, the linear calibration curves were achieved in the
range of 50-1000, 3-140, and 0.5-150MUM, with detection limits of 17.8, 1.44 and
0.29MUM for AA, DA, and UA, respectively. This work demonstrated that the removal
of additives of the graphene ink after film coating could be applied as a simple
and cost-effective electrochemical platform for sensing application.
PMID- 29332807
TI - Preliminary survey of matrix effects in the Microwave-sustained, Inductively
Coupled Atmospheric-pressure Plasma (MICAP).
AB - Matrix effects caused by Na and Al in the nitrogen Microwave-sustained,
Inductively Coupled, Atmospheric-pressure Plasma (MICAP) were investigated.
Easily ionizable elements, such as Na, can suppress or enhance the analyte
signal; Al is shown here to produce a similar effect. The influence of these
matrices was examined for 18 emission lines of 8 analyte atoms and ions having a
wide range of excitation and ionization energies. The plasma operating conditions
were fixed during all experiments at a total nitrogen flow of 19.4Lmin-1 and a
microwave power of 1.5kW. An Fe solution was used to determine the excitation
temperature of the plasma by the Boltzmann plot method at selected matrix
concentrations. In addition, vertical emission profiles of the plasma were
measured. The matrix effect becomes worse at higher concentrations of an easily
ionizable element. The effect is caused not only by a shift in ionization
equilibrium but also by a possible change in plasma ionization temperature.
Correction methods to reduce the matrix effects were tested and are discussed.
PMID- 29332808
TI - A polyethyleneimine-modified attapulgite as a novel solid support in matrix solid
phase dispersion for the extraction of cadmium traces in seafood products.
AB - In current study, a new polyethyleneimine (PEI)-modified attapulgite material was
prepared serving as a solid support in matrix solid-phase dispersion for the
extraction and determination (by atomic absorption spectrometry) of cadmium in
seafood products. The major factors affecting PEI grafting were optimized using
various PEI amounts and molecular weights. Parameters pivotal to MSPD extraction
efficiency, like: pH, volume of eluting solvent, and the sorbent mass-to-sample
ratio were investigated. Quantitative recoveries were achieved with 0.21g of fish
sample, 0.13g of PEI-modified attapulgite dispersing agent, and 50% HNO3 eluting
solution. The limit of detection and the limit of quantification were found to be
2.5 and 8.3MUgkg-1 for cadmium in surimi samples, respectively. The recoveries
were in the range of 89.2-100.1%, with RSDs ranged from 3.0% to 7.9% (n = 5).
When compared to the method stipulated by the Chinese National Standard GB
5009.15-2014, the newly developed MSPD provides comparable accuracy and even
better repeatability for the analysis of the cadmium in real seafood samples.
PMID- 29332809
TI - Peroxidase-catalyzed chemiluminescence system and its application in immunoassay.
AB - Peroxidases are widely used as catalysts in chemiluminescence (CL) reaction
because of their excellent catalytic activity and various selectable species,
such as horseradish peroxidase (HRP), sweet potato peroxidase (SPP) and soybean
peroxidase (SbP). They have been employed in many different CL systems for the
determination of hydrogen peroxidase (H2O2), nucleic acid, protein and so on. In
this paper, the application of peroxidases in the most commonly used luminol-H2O2
CL system was reviewed from two aspects of horseradish peroxidase (HRP) and some
anionic peroxidases. Thereinto, some enhancers used into HRP-catalyzed luminol
H2O2 CL system for higher sensitivity and lower detection limit were discussed
according to their classification. The employment of some anionic peroxidases
such as SPP and SbP in luminol-H2O2 CL system was also presented. The addition of
some specific enhancers into anionic peroxidase catalyzed luminol-H2O2 system
could lead to an increased light intensity and a relatively long-term stable
signal. The mechanism of all these enhanced luminol-H2O2 CL reaction and the
foundation of their analytical application were provided and reviewed in detail.
Finally, combined with the magnetic beads or nanoparticles as well as other
technologies, the characteristics of peroxidase-based luminol-H2O2 CL system were
summarized.
PMID- 29332810
TI - Sensitive fluorescence sensing of T4 polynucleotide kinase activity and
inhibition based on DNA/polydopamine nanospheres platform.
AB - 5'-Polynucleotide kinase (PNK) is a crucial enzyme that catalyzes the
phosphorylation of nucleic acid with 5'-OH termini and this phosphorylation
reaction has been involved in many important cellular activities. The evaluation
of PNK activity has received an increasing attention due to the significance of
PNK. Here, the polydopamine nanospheres (PDANS) could adsorb single-stranded DNA
(ssDNA) through pi-pi stacking or hydrogen bonding between nucleobases and
aromatic groups of PDANS, while the interaction between double-stranded DNA
(dsDNA) with PDANS was weakened due to the changed conformation. Hence, a novel
DNA/PDANS platform was constructed for the sensitive and selective determination
of T4 PNK activity based on the preferential binding properties of PDANS for
ssDNA over dsDNA and the excellent fluorescence quenching property of PDANS. The
dye-labeled dsDNA was phosphorylated by T4 PNK and then digested by lambda
exonuclease, yielding dye-labeled ssDNA, which would be adsorbed on the surface
of the PDANS and the fluorescence was greatly quenched by PDANS. Because of the
preferential binding properties of PDANS for ssDNA over dsDNA and the high
quenching property of PDANS, the developed DNA/PDANS platform exhibited good
analytical performance for T4 PNK sensing in complex biological matrix and
applied to screening inhibitors. The proposed DNA/PDANS based platform is
promising in developing high-throughput assays for drug screening and clinical
diagnostics.
PMID- 29332811
TI - Manufacture and application of RuO2 solid-state metal-oxide pH sensor to common
beverages.
AB - A new reproducible solid-state metal-oxide pH sensor for beverage quality
monitoring is developed and characterised. The working electrode of the developed
pH sensor is based on the use of laser-etched sputter-deposited RuO2 on Al2O3
substrate, modified with thin layers of sputter-deposited Ta2O5 and drop-cast
Nafion for minimisation of redox interference. The reference electrode is
manufactured by further modifying a working electrode with a porous polyvinyl
butyral layer loaded with fumed SiO2. The developed pH sensor shows excellent
performance when applied to a selection of beverage samples, with a measured
accuracy within 0.08 pH of a commercial glass pH sensor.
PMID- 29332812
TI - Thrombodynamics, a new global coagulation test: Measurement of heparin
efficiency.
AB - The actual coagulation status may be reliably measured using only highly
sensitive global functional tests; however, they are not numerous and all of them
have disadvantages. Thrombodynamics (TD), a novel global coagulation test, is
sensitive to hypo- and hypercoagulable states. The main properties of this test
were investigated, and its capabilities for hemostasis analysis were verified
through pharmacodynamic monitoring of the most widely used anticoagulants,
heparins. The anticoagulant effects in the plasma of donors (n = 20) and patients
after hip replacement (n = 20) spiked with unfractionated heparin or enoxaparin
were measured in vitro to eliminate the influence of pharmacokinetic factors.
Sensitivity for heparins was compared for activated partial thromboplastin time,
thrombin generation tests and TD. TD was shown to reliably characterize the
pharmacodynamics of any heparin in the entire range of its prophylactic and
therapeutic concentrations. Inter-individual variability for the anticoagulant
action of heparins was also calculated using the TD data. This variability did
not differ between the investigated groups and did not exceed 12% and 20% for the
stationary clot growth rate in the presence of unfractionated heparin and
enoxaparin, respectively. That finding was in accordance with the values
determined earlier using the thrombin generation test. The study results showed
that TD has advantages over the other global methods of coagulation analysis.
These advantages are good standardization, high reproducibility, independence of
the parameter values from patient age and gender, and a narrower parameter
distribution in a normal population. These results indicate that TD is a
promising universal assessment method that improves the quality of hemostasis
analysis because it more reliably detects deviations from the parameters'
reference values.
PMID- 29332813
TI - Fast and easy extraction of antidepressants from whole blood using ionic liquids
as extraction solvent.
AB - This study aims to prove that ionic liquids (ILs) can be used as extraction
solvents in a liquid-liquid microextraction, coupled to LC-MS/MS, for the
quantification of a large group of antidepressants in whole blood samples. The
sample preparation procedure consisted of adding 1.0mL aqueous buffer pH 3.0 and
60uL of IL (1-butyl-3-methylimidazolium hexafluorophosphate) to 1.0mL whole
blood. Subsequently, a 5-min rotary mixing step was performed followed by
centrifugation. The lower IL phase was collected, diluted 1:10 in methanol and
10uL was injected into the LC-MS/MS. The following analytes were included in the
full-quantitative method: agomelatine, amitriptyline, bupropion, clomipramine,
dosulepin, doxepin, duloxetine, escitalopram, fluoxetine, imipramine,
maprotiline, mianserin, mirtazapine, nortriptyline, paroxetine, reboxetine,
trazodone and venlafaxine. Selectivity was checked for 10 different whole blood
matrices. Additionally, possible interferences of deuterated standards or other
antidepressants were evaluated. Overall, no interferences were found. For each
analyte a matrix-matched calibration curve was constructed (7 levels, n = 6),
covering therapeutic and low toxic concentrations. Accuracy and precision were
evaluated over eight days, at three concentration levels (n = 2). Bias,
repeatability and intermediate precision results met with the proposed validation
criteria, except for fluvoxamine, which was therefore only included in the semi
quantitative method. LOQs were set at the lowest calibrator concentration and LOD
values were - for most analytes - within a range of 1-2ng/mL. Recoveries (RE) and
matrix effects (ME) were evaluated for five types of donor whole blood, at two
concentration levels. RE values were within a range of 53.11-132.98%. ME values
were within a range of 61.92-123.24%. In conclusion, this study proves the
applicability of ILs as extraction solvents for a large group of antidepressants
in complex whole blood matrices.
PMID- 29332814
TI - Novel S, N-doped carbon quantum dot-based "off-on" fluorescent sensor for silver
ion and cysteine.
AB - In this work, sulfur and nitrogen co-doped carbon dots (S,N-CQDs) as highly
selective fluorescent probe for silver ion (Ag+) and cysteine (Cys) detection
were designed and synthesized directly from citric acid and thiamine
hydrochloride via a one-step hydrothermal protocol in 63.8% quantum yield. This
probe enabled selective detection of Ag+ with a linear range of 0-10 and 10
250MUM and a limit of detection of 0.40MUM with respect to the variation in
fluorescence induced by target concentration and electron-transfer from S,N-CQDs
to Ag+. Furthermore, S,N-CQDs/Ag+ fluorescence can be effectively recovered by
virtue of a specific reaction of Cys with silver ion. This fluorescence "turn-on"
protocol was applied to determine Cys with two linear ranges of 0-10 and 10
120MUM as well as a detection limit of 0.35MUM. The corresponding cell
experiments were also performed, indicating that the prepared S,N-CQDs possessed
low cytotoxicity and good biocompatibility. Ultimately, the practicality and
viability of this fluorescent probe were demonstrated through the analysis of
silver ion in real river water and human serum samples.
PMID- 29332815
TI - Single particle analysis of TiO2 in candy products using triple quadrupole ICP
MS.
AB - Titanium dioxide (TiO2) belongs to the materials that have gained great
importance in many applications. In its particulate form (micro- or
nanoparticles), it has entered a huge number of consumer products and food-grade
TiO2, better known as E171 within the European Union, represents an important
food additive. Thus, there is an increasing need for analytical methods able to
detect and quantify such particles. In this regard, inductively coupled-mass
spectrometry (ICP-MS), in particular single particle ICP-MS (spICP-MS), has
gained importance due to its simplicity and ease of use. Nevertheless, the number
of applications for Ti nanoparticles is rather limited. In this study, we have
applied the spICP-MS strategy by comparing different measuring modes available in
triple quadrupole ICP-MS. First, single quadrupole mode using the
collision/reaction cell system was selected for monitoring the isotope 47Ti.
Different cell gases like He, O2 and NH3 were tested under optimised conditions
for its applicability in spICP-MS of standard suspensions of TiO2. The determined
analytical figures of merit were compared to those obtained by triple quadrupole
mode using the 47Ti or 48Ti reaction products using O2 and NH3 as reaction gases.
This comparison demonstrated that the triple quadrupole mode (TQ mode) was
superior in terms of sensitivity due to the more efficient removal of spectral
interferences. Particle size detection limits down to 26nm were obtained using
the best instrumental conditions for TiO2 particles at a dwell time of 10ms.
Finally, the different measuring modes were applied to the analysis of chewing
gum samples after a simple extraction procedure using an ultrasonic bath. The
obtained results showed a good agreement for the detected particle size range
using the different TQ modes. The size range of TiO2 particles was determined to
be between approximately 30 and 200nm, whereas roughly 40% of the particles were
smaller than 100nm. For the determination of the particle number concentration in
these real samples, we suggest CeO2 particles as internal standard.
PMID- 29332816
TI - Comparative enzymatic studies using ion-selective electrodes. The case of
cholinesterases.
AB - The application of traditional ion-selective electrodes for comparative enzymatic
analysis was demonstrated for the first time in this study. A kinetic
potentiometric method based on the monitoring of the concentration of the ionic
substrate involved in the enzymatic reaction catalyzed by different
cholinesterases is used for this purpose. A comparative study was performed
comprising both enzymatic assays using different ionic substrates and the
corresponding inhibited reactions in presence of neostigmine (a synthetic
anticholinesterase). The developed approach is used to obtain valuable
comparative results through calculation of kinetic parameters, such as Michaelis
and inhibition constants. Interesting results were obtained for
acetylcholinesterase and butyrylcholinesterase enzymes, which were selected as
proof-of-concept: (i) the binding affinity that these enzymes have for their
natural substrates showed to be higher (acetylcholine and butyrylcholine
respectively) than for their corresponding thiol derivatives (acetylthiocholine
and butyrylthiocholine), which are traditionally used in spectrophotometric
enzymatic assays; (ii) as expected, the maximum hydrolysis rate found in the
assays of each enzyme was independent of the substrate used; (iii)
acetylcholinesterase enzyme inhibition due to neostigmine was found to be higher
(higher inhibition constant). Advantageously, the use of ion-selective electrodes
permits to perform cholinesterases' enzymatic assays using their natural
substrates and under physiological conditions, unlike the traditional
spectrophotometric methods used in routine enzymatic assays. Importantly, while
well-known enzymes are use throughout this work, this approach can be extended to
other types of enzymatic assays as a tangible alternative to traditional
spectrophotometric methods.
PMID- 29332817
TI - Miniaturised electrically actuated high pressure injection valve for portable
capillary liquid chromatography.
AB - A miniaturised high pressure 6-port injection valve has been designed and
evaluated for its performance in order to facilitate the development of portable
capillary high performance liquid chromatography (HPLC). The electrically
actuated valve features a very small size (65 * 19 * 19mm) and light weight
(33g), and therefore can be easily integrated in a miniaturised modular capillary
LC system suited for portable field analysis. The internal volume of the
injection valve was determined as 98 nL. The novel conical shape of the stator
and rotor and the spring-loaded rotor performed well up to 32MPa (4641psi), the
maximum operating pressure investigated. Suitability for application was
demonstrated using a miniaturised capillary LC system applied to the
chromatographic separation of a mixture of biogenic amines and common cations.
The RSD (relative standard deviation) values of retention times and peak areas of
6 successive runs were 0.5-0.7% and 1.8-2.8% for the separation of biogenic
amines, respectively, and 0.1-0.2% and 2.1-3.0% for the separation of cations,
respectively. This performance was comparable with bench-top HPLC systems thus
demonstrating the applicability of the valve for use in portable and miniaturised
capillary HPLC systems.
PMID- 29332818
TI - A novel dual labeling approach enables converting fluorescence labeling reagents
into fluorogenic ones via introduction of purification tags. Application to
determination of glyoxylic acid in serum.
AB - Pre-column derivatization with fluorescence labeling reagents involves many
problems including crowded chromatograms, possibility of the introduction of
analytical errors, and poor selectivity. Herein we report a novel purification
tag/fluorophore dual labeling approach based on a multi-component reaction to
solve this major problem. Glyoxylic acid was recently identified as an early
biomarker for diabetes, thus it was selected as a model analyte for our new dual
labeling approach. Using the multi-component Petasis reaction, we could introduce
a fluorophore (1-pyreneboronic acid, 1-PyBA) and a purification tag (taurine) to
our target analyte (glyoxylic acid) in one step reaction. Using taurine as the
amine reactant in Petasis reaction leads to the formation of a reaction product
with a terminal sulfonic acid group which can be selectively retained on an anion
exchange sorbent allowing excess fluorescent 1-PyBA reagent and its fluorescent
decomposition products to be washed away. Then, quantification of the formed
analyte-fluorophore-purification tag adduct was carried out by a simple isocratic
HPLC-fluorescence detection method. The newly developed technique allowed highly
selective, very rapid and efficient determination of glyoxylic acid in human
serum eliminating endogenous components and excess reagent interference.
Glyoxylic acid was determined in serum at a final concentration down to 30nM (600
fmol/injection) with good recovery (87.0%), accuracy (- 2.2 to 9.2) and precision
(%RSD <= 8.7).
PMID- 29332819
TI - Chemometric analysis of NMR and GC datasets for chemotype characterization of
essential oils from different species of Ocimum.
AB - The genus Ocimum (Labiatae) comprises 30 species found in tropical and
subtropical regions of the planet, of which species O. basilicum L. and O.
gratissimum are widely used in food and traditional medicine. Phytochemical
studies on Ocimum have revealed a number of essential oil chemotypes, for
example, eugenol, methyl chavicol, linalool, and methyl cinnamate. Since
essential oils are commercially assessed according to their content, the aim of
this study was to develop a simple and precise method for their qualitative and
quantitative analysis using NMR spectroscopy combined with chemometrics. Seven
essential oils from different species of Ocimum, an unknown sample, and a
commercial sample were evaluated and the results compared to those from
established and precise GC-MS and GC-FID methods. Chemometric evaluation from
both 1H NMR and GC-MS data revealed three chemotypes: eugenol for O. gratissimum,
O. micranthum, and O. tenuiflorum; estragole for O. basilicum, O. basilicum var.
purpuracens, and O. selloi; and methyl cinnamate for O. americanum. The unknown
and commercial species were classified as cinnamate and eugenol chemotypes,
respectively. Despite the corroborating results, the chemometric analysis
revealed the higher robustness (better adjustment) of the 1H NMR model compared
to the GC-MS method in terms of certain statistical parameters. The 1H NMR method
allows for the detection and quantification of organic compounds in a complex
mixture without the need for certified standard compounds. Although GC-MS and GC
FID were able to detect five compounds not observed by NMR spectroscopy, the four
most important metabolites (eugenol, estragole, methyl cinnamate, and eucalyptol)
were more readily detected and quantified by 1H NMR.
PMID- 29332820
TI - A strategy for screening of alpha-glucosidase inhibitors from Morus alba root
bark based on the ligand fishing combined with high-performance liquid
chromatography mass spectrometer and molecular docking.
AB - A new method based on ligand fishing combined with high-performance liquid
chromatography quadrupole-time-of-flight mass spectrometer and molecular docking
was established to screen alpha-glucosidase inhibitors from a traditional Chinese
medicine Morus alba root bark. alpha-Glucosidase was immobilized on magnetic
nanoparticles, used as a solid support to incubate with crude extract. After
ligand fishing, the eluates were analyzed by high-performance liquid
chromatography quadrupole-time-of-flight mass spectrometer, obtaining eleven
ligands (1-4, 6-12) eventually. In order to discriminate the non-specific binders
and discover powerful enzyme inhibitors, molecular docking was further performed
and three of the eleven ligands were optimized to be excellent alpha-glucosidase
inhibitors by the confirmation of isolation and bioassay of individual compounds.
These three ligands, sanggenons G (6), O (7) and sanggenol G (12) exhibited
striking inhibitory activities with extremely low IC50 values. The results
suggest that established method will be applied to a wide range of target protein
to screen potential bioactive constituents from herbal medicines.
PMID- 29332821
TI - Determination of pyrophosphate and sulfate using polyhexamethylene guanidine
hydrochloride-stabilized silver nanoparticles.
AB - Positively charged polyhexamethylene guanidine hydrochloride-stabilized silver
nanoparticles (PHMG-AgNPs) were prepared and applied as a colorimetric probe for
single-step determination of pyrophosphate and sulfate. The approach is based on
the nanoparticles aggregation leading to change in their absorption spectra and
color of the solution. Due to both electrostatic and steric stabilization these
nanoparticles show decreased sensitivity relatively to many common anions, which
allows for simple and rapid direct single-step determination of pyrophosphate and
sulfate. Effects of different factors (time of interaction, pH, concentrations of
anions and the nanoparticles) on aggregation of PHMG-AgNPs and analytical
performance of the procedure were investigated. The method allows for the
determination of pyrophosphate and sulfate in the range of 0.16-2MUgmL-1 and 20
80MUgmL-1 with RSD of 2-5%, respectively. The analysis can be performed using
either spectrophotometry or naked-eye detection. Practical application of the
method was shown by the example of pyrophosphate determination in baking powder
sample.
PMID- 29332822
TI - Constituting fully integrated colorimetric analysis system for Fe(III) on
multifunctional nitrogen-doped MoO3/cellulose paper.
AB - Using ammonium molybdate and thiourea as precursors, nitrogen-doped MoO3 was
produced by a one-step carbonization and then fixed into the cellulose filter
paper (NMCP) with acrylic resin as a fixative. NMCP was designed as a
multifunctional nanocomposite, i.e., solid phase adsorbent for Fe(III)
preconcentration, photocatalyst for iron species transformation and color
interference removal, and colorimetric sensor for Fe(III) determination. After
photocatalysis, the complex of Fe-humic substances could be transformed into
Fe(III) ions, the interference of colored organic matter (e.g., aqueous humic
substance) was removed, Fe(III) was enriched selectively onto NMCP with the
coexistence of interference metal ions (e.g. Co(II) and Cd(II)) and then
transformed into Fe(II) by hydroxylamine and photoreduction and for colorimetric
analysis. The obstacle of o-phenanthroline colorimetric method was overcome. The
photodegradation activity of MoO3 was improved 2.02 times by nitrogen doping with
the optimal mass ratio, which was also 5.11 times of P25-TiO2. The concentration
of Fe(III) on NMCP was quantified by the gray-scale using smart phones and image
processing software, without complicated equipment. Based on multifunctional
NMCP, a fully integrated visual analysis system was proposed and suitable for the
field detection of Fe(III) in natural water. The log-linear calibration curve for
Fe(III) was in the range of 0.05-5mg/L with a determination coefficient (R2) of
0.976 and detection limit of 15MUg/L.
PMID- 29332823
TI - A combination of computational-experimental study on metal-organic frameworks MIL
53(Al) as sorbent for simultaneous determination of estrogens and glucocorticoids
in water and urine samples by dispersive micro-solid-phase extraction coupled to
UPLC-MS/MS.
AB - In this work, computational and experimental methods were used to study the
adsorption of estrogens and glucocorticoids on metal-organic frameworks (MOFs).
Computer-aided molecular simulation was applied to predict the adsorption of
eight analytes on four MOFs (MIL-101(Cr), MIL-100(Fe), MIL-53(Al), and UiO
66(Zr)) by examining molecular interactions and calculating free binding
energies. Subsequently, the four water-stable MOFs were synthesized and evaluated
as adsorbents for the target hormones in aqueous solution. As the MOF exhibiting
the highest adsorption capacity in both computations and experiments, MIL-53(Al)
was chosen as a sorbent to develop a dispersive micro-solid-phase extraction
procedure coupled to ultra-performance liquid chromatography tandem mass
spectrometry for simultaneous determination of the target analytes in water and
human urine samples. Experimental parameters affecting the extraction recoveries,
including pH, ionic strength, MIL-53(Al) amount, extraction time, desorption
time, and desorption solvent, were optimized. The optimized method provided a
linear range of 0.005025-368.6MUg/L with good correlation coefficients (0.9982 <=
r2 <= 0.9992), and limits of detection (S/N = 3) and quantification (S/N = 10) of
0.0015-1.0MUg/L and 0.005-1.8MUg/L, respectively. The analyte recoveries were in
the range of 80.6-98.4% in water samples and 88.4-93.2% in urine samples.
Furthermore, MIL-53(Al) showed good stability over 10 extraction cycles (RSD <
10.0%). Good agreement between experimental measurements and computational
results showed the potential of this approach for elucidating adsorption
mechanisms and predicating extraction efficiencies for MOFs and targets,
providing new directions for the development and utilization of MOFs.
PMID- 29332824
TI - Dithiothreitol-based protein equalization technology to unravel biomarkers for
bladder cancer.
AB - This study aimed to assess the benefits of dithiothreitol (DTT)-based sample
treatment for protein equalization to assess potential biomarkers for bladder
cancer. The proteome of plasma samples of patients with bladder carcinoma,
patients with lower urinary tract symptoms (LUTS) and healthy volunteers, was
equalized with dithiothreitol (DTT) and compared. The equalized proteomes were
interrogated using two-dimensional gel electrophoresis and matrix assisted laser
desorption ionization time of flight mass spectrometry. Six proteins, namely
serum albumin, gelsolin, fibrinogen gamma chain, Ig alpha-1 chain C region, Ig
alpha-2 chain C region and haptoglobin, were found dysregulated in at least 70%
of bladder cancer patients when compared with a pool of healthy individuals. One
protein, serum albumin, was found overexpressed in 70% of the patients when the
equalized proteome of the healthy pool was compared with the equalized proteome
of the LUTS patients. The pathways modified by the proteins differentially
expressed were analyzed using Cytoscape. The method here presented is fast,
cheap, of easy application and it matches the analytical minimalism rules as
outlined by Halls. Orthogonal validation was done using western-blot. Overall,
DTT-based protein equalization is a promising methodology in bladder cancer
research.
PMID- 29332825
TI - Development of Gd3+-immobilized glutathione-coated magnetic nanoparticles for
highly selective enrichment of phosphopeptides.
AB - In this study, we designed a gadolinium-based immobilized metal ion affinity
chromatography material for the selective enrichment of phosphopeptides.
Gadolinium ion was immobilized on the surface of glutathione-coated magnetic
nanoparticles through a facile and effective synthetic route. The adsorbent
integrated the advantages of superparamagnetism of Fe3O4 core, good biological
compatibility of glutathione, and strong interaction between gadolinium ion and
phosphopeptides. It was employed to enrich phosphopeptides from standard protein
digests coupled with MALDI-TOF MS. Results demonstrated that the adsorbent
possessed high selectivity for phosphopeptides, good reusability and
reproducibility. Moreover, the material provided selective enrichment of
phosphopeptides from real samples including non-fat milk digests and human serum.
The developed method exhibited high sensitivity (detection limit of 10 fmol),
showing great potential in the detection of low-abundance phosphopeptides in
biological samples.
PMID- 29332826
TI - A robust and extendable sheath flow interface with minimal dead volume for
coupling CE with ESI-MS.
AB - In this paper, we describe a robust sheath flow-based CE-MS interface with
minimal interface dead volume based on an extended pattern. A 20um i.d. * 90um
o.d. fused-silica capillary with a chemically-etched thin-wall tip (30um o.d.)
was used as the separation capillary as well as electrospray emitter, and a 200um
i.d. * 375um o.d. capillary with a tapered tip (40um o.d.) was used as the sheath
flow capillary. An extendable sheath-flow interface mode was adopted by
decreasing the thickness of separation capillary tip and extending the separation
capillary tip out from the sheath flow capillary tip, and allowing the sheath
flow to be transferred to the separation capillary tip along its outer surface,
forming a surface sheath flow to mix with sample flow at the separation capillary
tip. Such a strategy could significantly reduce the interface dead volume and
thus improve the CE separation efficiency and detection sensitivity, as well as
evidently enhance the working reliability of the CE-MS interface. We investigated
various factors affecting the interface performance, including capillary
extending distance, emitter diameters, sheath flow capillary shape, and sheath
flow rate. Under the optimized conditions, a minimal interface dead volume of ca.
4pL was obtained which is the smallest one compared with previously-reported
sheath flow-based CE-MS interfaces. The feasibility and applicability of the
present CE-MS interface were demonstrated in the separation of a peptide mixture
with high separation efficiency of 2.07-3.38um plate heights and good
repeatabilities (< 6.1% RSD, n = 5). We except such a simple and robust interface
could provide a possible solution for the development of commercial CE-MS
interfaces differing from the currently-used ones, and has the potentials to be
applied in routine analytical laboratories for various studies such as
proteomics, metabolomics, or single cell analysis.
PMID- 29332827
TI - Rapid and sensitive detection of malachite green in aquaculture water by
electrochemical preconcentration and surface-enhanced Raman scattering.
AB - A highly sensitive and rapid method of in-situ surface-enhanced Raman
spectroscopy (SERS) combining with electrochemical preconcentration (EP) in
detecting malachite green (MG) in aquaculture water was established. Ag
nanoparticles (AgNPs) were synthesized and spread onto the surface of gold
electrodes after centrifuging to produce SERS-active substrates. After optimizing
the pH values, preconcentration potentials and times, in-situ EP-SERS detection
was carried out. A sensitive and rapid analysis of the low-concentration MG was
accomplished within 200s and the limit of detection was 2.4 * 10-16M.
PMID- 29332828
TI - UPLC-MS/MS analysis for antioxidant components of Lycii Fructus based on spectrum
effect relationship.
AB - Lycii Fructus is widely cultivated in the Northwest China. It is well-known for
its antiaging effect in traditional Chinese medicines (TCMs), but the effective
components are not clear. In this work, the ultra-performance liquid
chromatography tandem mass spectrometry (UPLC-MS/MS) was used to study the
antioxidant components of Lycii Fructus through analyzing the spectrum-effect
relationship, and the positive correlation components with antioxidant activity
were partially identified. The extractums of Lycii Fructus were adsorbed with
macroporous resin, and then eluted with water and 30%, 60%, 90% ethanol in turn.
The extract fraction eluted with 60% ethanol was determined as the best, and was
taken for subsequent experiments. With the above separation method, UPLC
fingerprints of thirty batches of Lycii Fructus (from different areas) were
obtained, and thirty common peaks were selected through similarity analysis (SA).
Combined with the data of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino
bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) assays, the
spectrum-effect relationship was studied. The results showed that the main peaks
with antioxidant activity were P14, P26, P8, and P21 for DPPH, and P26, P14, P21,
and P19 for ABTS. Using the UPLC-MS/MS data, peaks P14, P19, P21, and P30 were
respectively identified as chlorogenic acid, quercetin, kaempferol, and
isorhamnetin, and then the results were confirmed through comparison with the
standards and other references. Finally, their strong antioxidant activities were
validated experimentally.
PMID- 29332829
TI - Synchronous detection of ebolavirus conserved RNA sequences and ebolavirus
encoded miRNA-like fragment based on a zwitterionic copper (II) metal-organic
framework.
AB - From a three-dimensional (3D) metal-organic framework (MOF) of
{[Cu(Cmdcp)(phen)(H2O)]2.9H2O}n (1, H3CmdcpBr = N-carboxymethyl-(3,5
dicarboxyl)pyridinium bromide, phen = phenanthroline), a sensitive and selective
fluorescence sensor has been developed for the simultaneous detection of
ebolavirus conserved RNA sequences and ebolavirus-encoded microRNA-like (miRNA
like) fragment. The results from molecular dynamics simulation confirmed that MOF
1 absorbs carboxyfluorescein (FAM)-tagged and 5(6)-carboxyrhodamine,
triethylammonium salt (ROX)-tagged probe ss-DNA (probe DNA, P-DNA) by pi...pi
stacking and hydrogen bonding, as well as additional electrostatic interactions
to form a sensing platform of P-DNAs@1 with quenched FAM and ROX fluorescence. In
the presence of targeted ebolavirus conserved RNA sequences or ebolavirus-encoded
miRNA-like fragment, the fluorophore-labeled P-DNA hybridizes with the analyte to
give a P-DNA@RNA duplex and released from MOF 1, triggering a fluorescence
recovery. Simultaneous detection of two target RNAs has also been realized by
single and synchronous fluorescence analysis. The formed sensing platform shows
high sensitivity for ebolavirus conserved RNA sequences and ebolavirus-encoded
miRNA-like fragment with detection limits at the picomolar level and high
selectivity without cross-reaction between the two probes. MOF 1 thus shows the
potential as an effective fluorescent sensing platform for the synchronous
detection of two ebolavirus-related sequences, and offer improved diagnostic
accuracy of Ebola virus disease.
PMID- 29332830
TI - Novel approach in k0-NAA for highly concentrated REE Samples.
AB - The present paper presents a new approach for k0-NAA for accurate quantification
with short turnaround analysis times for rare earth elements (REEs) in high
content mineral matrices. REE k0 and Q0 values, spectral interferences and
nuclear interferences were experimentally evaluated and improved with Alfa Aesar
Specpure Plasma Standard 1000mgkg-1 mono-rare earth solutions. The new iterative
gamma-ray self-attenuation and neutron self-shielding methods were investigated
with powder standards prepared from 100mg of 99.9% Alfa Aesar mono rare earth
oxide diluted with silica oxide. The overall performance of the new k0-NAA method
for REEs was validated using a certified reference material (CRM) from Canadian
Certified Reference Materials Project (REE-2) with REE content ranging from
7.2mgkg-1 for Yb to 9610mgkg-1 for Ce. The REE concentration was determined with
uncertainty below 7% (at 95% confidence level) and proved good consistency with
the CRM certified concentrations.
PMID- 29332831
TI - Corrigendum to, Carboxylated carbon nanospheres as solid-phase extraction
adsorbents for the determination of perfluorinated compounds in water samples by
liquid chromatography-tandem mass spectrometry' [Talanta 178 (2018) 129-133].
PMID- 29332832
TI - Electrochemiluminescent detection of cardiac troponin I by using soybean
peroxidase labeled-antibody as signal amplifier.
AB - This work proposed an electrochemiluminescence (ECL) immunosensor for
quantitative monitoring of cardiac troponin I (cTnI) in plasma with soybean
peroxidase (SBP) labeled-antibody as signal amplifier. The ECL sandwich
immunosensor was constructed by covalent binding anti-cTnI capture antibody (Ab1)
to polyethylenimine-functionalized graphene matrix, which was obtained by a
simple hydrothermal reaction between polyethylenimine (PEI) and graphene oxide
(GO). After that, the SBP-labeled detection antibody (SBP-Ab2), synthesized by
NaIO4 method, was immobilized on the surface of electrode through sandwich
immunoreaction. The SBP on electrode surface displayed strong and stable ECL
signal of luminol in the presence of H2O2, which could be used for cTnI detection
with a concentration range of 5-30,000pg/mL and a detection limit of 3.3pg/mL.
This proposed SBP-modified immunosensor displayed high sensitivity, selectivity
and accuracy, and was expected not only to detect cTnI in practical human plasma
sample but also to be used in other biomarkers detection.
PMID- 29332833
TI - A combination of "thiol-ene" click chemistry and surface initiated atom transfer
radical polymerization: Fabrication of boronic acid functionalized magnetic
graphene oxide composite for enrichment of glycoproteins.
AB - An efficient glycoproteins enrichment platform is one of vital preprocessing
steps in biomarker research and in particular glycoproteomics. In this work, a
well-defined boronic acid functionalized magnetic graphene oxide nanocomposite
(Fe3O4-GO@PAAPBA) was synthesized for the selective enrichment of glycoproteins
from complex biological samples via a novel strategy based on the "thiol-ene"
click chemistry and surface initiated atom transfer radical polymerization (SI
ATRP). The initiator of ATRP was anchored to the surface of substrate through
"thiol-ene" click reaction. The product Fe3O4-GO@PAAPBA was successfully
synthesized in following SI-ATRP. The Fe3O4-GO@PAAPBA nanocomposite was
characterized by transmission electron microscopy (TEM), Fourier transform
infrared spectroscopy (FTIR), X-ray diffraction (XRD), X-ray photoelectron
spectroscopy (XPS), vibrating sample magnetometry (VSM) and thermogravimetric
analysis. The adsorption capacity of Fe3O4-GO@PAAPBA towards ovalbumin (OVA) and
transferrin (Trf) is 471mgg-1 and 450mgg-1, respectively. The nanocomposite also
featured good selectivity to glycoproteins in the mixture of glycoproteins and
non-glycoproteins at alkaline (pH 9.0) and physiological conditions (pH 7.4).
Furthermore, it can be applied to extract glycoproteins directly from egg white
samples. These results have indicated that Fe3O4-GO@PAAPBA was a potential
affinity material in glycoprotein analysis.
PMID- 29332834
TI - Direct inlet probe ion mobility spectrometry.
AB - Direct inlet probe (DIP) was used as an introduction and a pre-separation step
for atmospheric pressure photoionization time-of-flight ion mobility spectrometry
(APPI-TOF-IMS) for the first time. IMS is an analytical technique used to
separate and identify ionized molecules in the gas phase and under atmospheric
pressure based on their mobility. The utilization of DIP prior to IMS gives the
possibility to introduce the analytes into the gas phase and provides an
additional separation based on their vapor pressure. The proof-of-principle study
was done on example of eight polycyclic aromatic hydrocarbons (PAHs) with the
ring number from 2 to 5, namely naphthalene, fluorene, anthracene, phenanthrene,
pyrene, fluoranthene, benzo[a]pyrene, and benzo[k]fluoranthene. All these
compounds are included in EPA priority pollutant list. Moreover, benzo[a]pyrene
and benzo[k]fluoranthene are marked by EPA as probably carcinogen compounds and
also included into SCF and EU lists. To increase the sensitivity of DIP-APPI-IMS
the analysis was performed using a dopant assisted ionization method (benzene,
74mgL-1 in N2). It was found that the heating rate of the interface plays a
crucial role for the whole analytical procedure. To prove the ability of this
method to analyze PAHs in the mixture, the mixtures containing up to five PAHs
were analyzed. The LODs for the analyzed compounds obtained with DIP-APPI-IMS
were found to be in the tens- or hundreds-of-microgram-per-liter range. The
obtained results are promising enough to ensure the potential of DIP as an
introduction and a pre-separation step for ion mobility based methods.
PMID- 29332835
TI - Varietal discrimination of hop pellets by near and mid infrared spectroscopy.
AB - Hop is one of the most important ingredients of beer production and several
varieties are commercialized. Therefore, it is important to find an eco-real-time
friendly-low-cost technique to distinguish and discriminate hop varieties. This
paper describes the development of a method based on vibrational spectroscopy
techniques, namely near- and mid-infrared spectroscopy, for the discrimination of
33 commercial hop varieties. A total of 165 samples (five for each hop variety)
were analysed by both techniques. Principal component analysis, hierarchical
cluster analysis and partial least squares discrimination analysis were the
chemometric tools used to discriminate positively the hop varieties. After
optimizing the spectral regions and pre-processing methods a total of 94.2% and
96.6% correct hop varieties discrimination were obtained for near- and mid
infrared spectroscopy, respectively. The results obtained demonstrate the
suitability of these vibrational spectroscopy techniques to discriminate
different hop varieties and consequently their potential to be used as an
authenticity tool. Compared with the reference procedures normally used for hops
variety discrimination these techniques are quicker, cost-effective, non
destructive and eco-friendly.
PMID- 29332836
TI - Fluorescent and colorimetric dual-mode aptasensor for thrombin detection based on
target-induced conjunction of split aptamer fragments.
AB - Since the lack of detection diversity of the single-signal readout strategy, it
is urgent to develop fast and multisignal assay strategies. A highly selective
and sensitive assay method with colorimetric and fluorometric dual signals
readouts is presented in this paper. It is based on the principle that the target
induced conjunction of split aptamer fragments assembled on the surface of Au
nanoparticles (AuNPs). In the presence of targets, the color of solution changed
from wine red to blue and can be measured both visual inspection and
spectrophotometry because of the aggregation of AuNPs. At the same time, the
report probes which are original hybrid with the anchoring aptamer fragments on
the AuNPs surface can be released and recovers the fluorescence. By use of this
detection strategy, the limit of detection for thrombin (TMB), as a model of
analyte, were 0.45 and 0.16nM, respectively. Furthermore, this protocol can
discriminate TMB from other analogue with high selectivity and can be used to
detect TMB in human serum samples. The results came from the two signals were
well consistent with each other, which demonstrated that it has application
potential for detection of TMB in complex matrix.
PMID- 29332837
TI - A novel electroanalytical assay for sulfamethazine determination in food samples
based on conducting polymer nanocomposite-modified electrodes.
AB - The toxicity of sulfa drugs has attracted great attention, and the reported
electrochemical methods for sulfa drugs usually employ a high oxidation
potential. In this work, a one-pot synthesized conducting polymer nanocomposite
containing poly(3,4-ethylenedioxythiophene) (PEDOT) and MnO2 was cast on a screen
printed carbon electrode (SPCE), and the modified electrode showed superior
electrochemical activity over a bare electrode for sulfamethazine (SMZ)
determination. The SMZ detection was based on the electrochemical oxidation
product, which showed an adsorptive property and exhibited a redox couple at
0.39V in pH 3 phosphate buffer solutions (PBS). The electrode surfaces were well
characterized by the water contact angle technique, Raman spectroscopy, X-ray
photoelectron spectroscopy (XPS), field emission scanning electron microscopy (FE
SEM), atomic force microscopy (AFM) and cyclic voltammetry. By the use of square
wave voltammetry (SWV), a wide linear response to SMZ, from 1.0uM to 500MUM, was
obtained. The sensitivity and detection limits (S/N = 3) were 0.115MUAMUM-1 and
0.16MUM, respectively. The proposed method and a reference high-performance
liquid chromatographic method (HPLC) were applied for the determination of SMZ in
two real samples using the standard addition method, and satisfactory recoveries
and good agreement were obtained.
PMID- 29332838
TI - Rapid and sensitive tapered-capillary microextraction combined to on-line sample
stacking-capillary electrophoresis for extraction and quantification of two beta
blockers in human urine.
AB - A tapered-capillary microextraction (tCap-MUEx) combining with field-amplified
stacking (FASI) method for CE analysis was developed. The tCap-MUEx method is
based on the construction of a micro solid phase extraction (SPE) column by
narrowing the end of a silica capillary from 530um (inner diameter) to 20um,
enabling the packing of 45um sorbent particles without a frit. Various parameters
that may affect the microextraction and FASI-CE analysis have been investigated
and optimized. This study shows that microextraction exhibits advantages of small
sample and sorbent volumes (less than 200MUL sample and 2MUL sorbent) and fast
extraction time of 6min. The method was successfully applied for efficient
determination of atenolol and metoprolol in human urine samples, with recovery of
93.7-105.5% and RSD (n=3) lower than 8.5%. Twenty-one-fold and nineteen-fold
average enhancement of detection sensitivity was achieved for atenolol and
metoprolol, respectively, versus the CE method without tCap-MUEx and FASI. The
method is environmentally friendly and allows reuse of the sorbent at least 8
times without an obvious loss in performance. The results indicate that the
proposed method could be potentially applied in a wide range of doping control,
clinical, forensic toxicology, food analysis and environmental analyses.
PMID- 29332839
TI - Magnetic solid-phase extraction based on magnetic multiwalled carbon nanotubes
for the simultaneous enantiomeric analysis of five beta-blockers in the
environmental samples by chiral liquid chromatography coupled with tandem mass
spectrometry.
AB - In this work, the magnetic multiwalled carbon nanotubes (Mag-MWCNTs) were
prepared by self-assembly method and characterized by scanning electron
microscopy, X-ray powder diffraction, energy dispersive X-ray and vibrating
sample magnetometer. Then, these synthetic Mag-MWCNTs were used as sorbents to
extract five beta-blockers (atenolol, metoprolol, esmolol, pindolol and
arotinolol) by magnetic solid-phase extraction. The target analytes adsorbed on
Mag-MWCNTs were eluted and determined on a chiral alpha-acid glycoprotein column
coupled with a triple quadrupole mass spectrometry. Eventually, the proposed
method was applied to the analysis of the enantiomeric composition of the studied
beta-blockers in three environmental samples, including river water, influent
wastewater and effluent wastewater. Method detection and quantification limits
for all enantiomers were in the range of 0.50-1.45 and 1.63-3.75ng/L,
respectively. Satisfactory recovery (82.9-95.6%), good intra-day precision (RSD
0.4-10.4%) and inter-day precision (RSD 2.9-7.4%) were also obtained. With
numerous advantages such as simplicity of operation, rapidity and high enrichment
factor, the newly developed method has potential to assess the enantioselectivity
of chiral drugs in ecotoxicity and biodegradation processes, which is also a new
expanded application of Mag-MWCNTs in the environmental analysis.
PMID- 29332841
TI - Improved neuron culture using scaffolds made of three-dimensional PDMS micro
lattices.
AB - Tissue engineering strives to create functional components of organs with
different cell types in vitro. One of the challenges is to fabricate scaffolds
for three-dimensional (3D) cell culture under physiological conditions. Of
particular interest is the investigation of the morphology and function of the
central nervous system cultured using such scaffolds. Here, we used an elastomer
polydimethylsiloxane (PDMS)-to produce lattice-type scaffolds from a
photolithography-defined template. The photomask with antidot arrays was spin
coated by a thick layer of resist, and was downward mounted on a rotating stage
at an angle of 45 degrees . After the exposure was repeated three or more times,
maintaining the same exposure plan but rotated by the same angle, a photoresist
was developed to produce a 3D porous template. Afterwards, a pre-polymer mixture
of PDMS was poured in and cured, followed by a resist etch, resulting in lattice
type PDMS features. Before cell culture, the PDMS lattices were surface
functionalized. A culture test was conducted using NIH-3T3 cells and primary
hippocampal cells from rats, showing homogenous cell infiltration and 3D
attachment. As expected, a much higher cell number was found in the 3D PDMS
lattices compared to the 2D culture. We also found a higher neuron-to-astrocyte
ratio and a higher degree of cell ramification in the 3D culture compared to the
2D culture due to the change of scaffold topography and the elastic properties of
the PDMS micro-lattices. Our results demonstrate that the 3D PDMS micro-lattices
improve the survival and growth of cells, as well as the network formation of
neurons. We believe that such an enabling technology is useful for research and
clinical applications, including disease modeling, regenerative medicine, and
drug discovery/drug cytotoxicity studies.
PMID- 29332842
TI - Ligand-cascading nano-delivery devices to enable multiscale targeting of anti
neurodegenerative therapeutics.
AB - Neurodegenerative diseases are a debilitating set of conditions that affect a
significant fraction of the world's population, and this fraction is expected to
increase as the population ages. Many therapeutic strategies have been explored
to treat the pathological mechanisms of neurodegenerative diseases, but multiple
sequential hurdles to central nervous system (CNS) delivery, including the blood
brain barrier (BBB), diseased neuronal membranes, and the organelle barrier, make
drug delivery challenging and necessitate the use of innovative strategies to
target and cross each barrier. Advances in drug delivery technology have the
potential to improve the standard of treatment for neurodegenerative diseases by
enhancing local drug concentration at the pathologically relevant cells and
organelles. Furthermore, ligand-cascading nano-delivery devices could address
these issues by sequentially presenting targeting ligands for crossing each of
the aforementioned hurdles. In this review, we provide an overview of ligand
technologies that enable BBB transcytosis, localization to or internalization in
diseased neuronal cells, and localization at the organelle of interest. We
summarize recent strategies for sequentially presenting pertinent ligands at each
hurdle to CNS delivery. These ligand-cascade strategies will enable rational
design of nano-delivery devices for multiscale targeting of anti
neurodegenerative therapeutics.
PMID- 29332840
TI - Examining patterns of multimorbidity, polypharmacy and risk of adverse drug
reactions in chronic obstructive pulmonary disease: a cross-sectional UK Biobank
study.
AB - OBJECTIVE: This study aims: (1) to describe the pattern and extent of
multimorbidity and polypharmacy in UK Biobank participants with chronic
obstructive pulmonary disease (COPD) and (2) to identify which comorbidities are
associated with increased risk of adverse drug reactions (ADRs) resulting from
polypharmacy. DESIGN: Cross-sectional. SETTING: Community cohort. PARTICIPANTS:
UK Biobank participants comparing self-reported COPD (n=8317) with no COPD (n=494
323). OUTCOMES: Multimorbidity (>=4 conditions) and polypharmacy (>=5
medications) in participants with COPD versus those without. Risk of ADRs (taking
>=3 medications associated with falls, constipation, urinary retention, central
nervous system (CNS) depression, bleeding or renal injury) in relation to the
presence of COPD and individual comorbidities. RESULTS: Multimorbidity was more
common in participants with COPD than those without (17% vs 4%). Polypharmacy was
highly prevalent (52% with COPD taking >=5 medications vs 18% in those without
COPD). Adjusting for age, sex and socioeconomic status, those with COPD were
significantly more likely than those without to be prescribed >=3 medications
contributing to falls (OR 2.27, 95% CI 2.13 to 2.42), constipation (OR 3.42, 95%
CI 3.10 to 3.77), urinary retention (OR 3.38, 95% CI 2.94 to 3.87), CNS
depression (OR 3.75, 95% CI 3.31 to 4.25), bleeding (OR 4.61, 95% CI 3.35 to
6.19) and renal injury (OR 2.22, 95% CI 1.86 to 2.62). Concomitant cardiovascular
disease was associated with the greatest risk of taking >=3 medications
associated with falls/renal injury. Concomitant mental health conditions were
most strongly associated with medications linked with CNS depression/urinary
retention/bleeding. CONCLUSIONS: Multimorbidity is common in COPD and associated
with high levels of polypharmacy. Co-prescription of drugs with various ADRs is
common. Future research should examine the effects on healthcare outcomes of co
prescribing multiple drugs with similar potential ADRs. Clinical guidelines
should emphasise assessment of multimorbidity and ADR risk.
PMID- 29332843
TI - Intrinsic electron trapping in amorphous oxide.
AB - We demonstrate that electron trapping at intrinsic precursor sites is endemic in
non-glass-forming amorphous oxide films. The energy distributions of trapped
electron states in ultra-pure prototype amorphous (a)-HfO2 insulator obtained
from exhaustive photo-depopulation experiments demonstrate electron states in the
energy range of 2-3 eV below the oxide conduction band. These energy
distributions are compared to the results of density functional calculations of a
HfO2 models of realistic density. The experimental results can be explained by
the presence of intrinsic charge trapping sites formed by under-coordinated Hf
cations and elongated Hf-O bonds in a-HfO2. These charge trapping states can
capture up to two electrons, forming polarons and bi-polarons. The corresponding
trapping sites are different from the dangling-bond type defects responsible for
trapping in glass-forming oxides, such as SiO2, in that the traps are formed
without bonds being broken. Furthermore, introduction of hydrogen causes
formation of somewhat energetically deeper electron traps when a proton is
immobilized next to the trapped electron bi-polaron. The proposed novel mechanism
of intrinsic charge trapping in a-HfO2 represents a new paradigm for charge
trapping in a broad class of non-glass-forming amorphous insulators.
PMID- 29332844
TI - Understanding carbon nanotube channel formation in the lipid membrane.
AB - Carbon nanotubes (CNTs) have been considered a prominent nano-channel in cell
membranes because of their prominent ion-conductance and ion-selectivity,
offering agents for a biomimetic channel platform. Using a coarse-grained
molecular dynamics simulation, we clarify a construction mechanism of vertical
CNT nano-channels in a lipid membrane for a long period, which has been difficult
to observe in previous CNT-lipid interaction simulations. The result shows that
both the lipid coating density and length of CNT affect the suitable fabrication
condition for a vertical and stable CNT channel. Also, simulation elucidated that
a lipid coating on the surface of the CNT prevents the CNT from burrowing into
the lipid membrane and the vertical channel is stabilized by the repulsion force
between the lipids in the coating and membrane. Our study provides an essential
understanding of how CNTs can form stable and vertical channels in the membrane,
which is important for designing new types of artificial channels as biosensors
for bio-fluidic studies.
PMID- 29332845
TI - N-doped ZnO nanosheets: towards high performance two dimensional catalysts.
AB - Recently, catalytic activity of atomically thin two dimensional (2D) materials
has attracted great interest. In this paper, via first principles calculations,
we show for the first time that N-doped 2D one-atom-thick ZnO nanosheets exhibit
high catalytic activity towards CO oxidation. A pristine 2D ZnO nanosheet is
chemically inert and as a result, CO and O2 molecules do not chemically bind on
the nanosheet. Our calculations predict that the N doping activates the ZnO
sheet, leading to strong CO and O2 adsorptions. We further show that the CO
oxidation catalyzed by the N-doped 2D ZnO sheet has a low reaction barrier around
0.5 eV. Besides high catalytic activity, the N-doped 2D ZnO sheet also
demonstrates intriguing electronic and magnetic properties. These findings
provide new opportunities for the future development of high performance 2D
catalysts.
PMID- 29332846
TI - Using Concept Mapping to Explore and Engage Parent and Youth Residents of an
Economically Underserved Minority Community around Children's Asthma.
PMID- 29332847
TI - Using Concept Mapping to Explore and Engage Parent and Youth Residents of an
Economically Underserved Minority Community around Children's Asthma.
AB - BACKGROUND: Asthma continues to disproportionately impact children living in
economically underserved urban neighborhoods, and contributes to persistent
racial and economic disparities in health. Furthermore, asthma is often
exacerbated by the presence of social and environmental factors that are
prevalent in, and sometimes particular to, these communities. OBJECTIVES: The
present study uses a community-based participatory research (CBPR) approach to
explore and define the experience and issues around children's asthma in an
economically underserved community. These findings will be used to inform the
design of a community intervention. METHODS: Through a community and academic
partnership called Healthy Living, Healthy Learning, Healthy Lives (HL3), we
engaged neighborhood youth and adult residents (N = 21) in a concept mapping
activity to identify triggers and health care-related factors that influence
children with asthma. RESULTS: Findings highlight that the most important
triggers of asthma included indoor and outdoor irritants and allergens, as well
as violence and fear-related emotions. The most important factors perceived to
influence the care of asthma included medical relievers such as asthma
medication, appliances such as a humidifier, and supports for asthma like the
school nurse. Differences between adults and youth perceptions of factors
triggering and influencing asthma are highlighted. CONCLUSIONS: Engaging
community residents as experts provided a deeper understanding of the issues
around children's asthma in the community, which can contribute to the design of
a more effective intervention.
PMID- 29332849
TI - Combined Diabetes Prevention and Disease Self-Management Intervention for
Nicaraguan Ethnic Minorities: A Pilot Study.
AB - BACKGROUND: Informed by formative community-based participatory research (CBPR),
we developed a combined model of diabetes prevention and self-management.
OBJECTIVES: To assess the feasibility, acceptability, and preliminary efficacy of
our CBPR-inspired model. METHODS: A mixed methods study was conducted using a pre
experimental design. The setting was a church-based clinic located on Nicaragua's
rural Atlantic coast. Miskitos and Creoles with or at risk for diabetes were
sampled. Preliminary efficacy was assessed with A1C, weight, and quality of life
(QOL) measures at baseline, 3 months, and 6 months. An open-ended survey assessed
intervention satisfaction. The 8-week, registered nurse (RN)-led intervention
emphasized knowledge acquisition and behavioral strategies for dietary, physical
activity, and medication regimen adherence. Paired t tests were computed to
assess preliminary efficacy. Content analysis was conducted to assess
intervention acceptability. RESULTS: A total of 42 participants were enrolled.
For participants completing follow-up data collection (n = 33), mean A1C improved
from 8.8% to 8.3% (t = -2.19; p = .04) from baseline to 3 months. Among
participants with a baseline A1C of greater than 7.5% (n = 24), the mean A1C
decreased from 9.7% to 9.0% from baseline to 3 months (t = -2.86; p = .01), and
to 8.7% at 6 months (t = -3.00; p = .01). Nonsignificant weight changes were
observed. Mental health QOL improved, on average from baseline to 3 months (t =
2.20; p = .04) and 6 months (t = 4.7; p < .01) for the sample. An increase in
mean physical health QOL was observed from baseline to 3 months (t = 2.91; p <
.01). The intervention was found to be acceptable. Study feasibility was good,
with successful research capacitation and achievement of sampling goals.
CONCLUSIONS: Findings suggest our novel intervention holds promise for wider
application to reduce diabetes burden among Nicaraguan ethnic minorities.
PMID- 29332850
TI - Community Advisory Boards Guiding Engaged Research Efforts within a Clinical
Translational Sciences Award: Key Contextual Factors Explored.
AB - BACKGROUND: Engaging stakeholders in research carries the promise of enhancing
the research relevance, transparency, and speed of getting findings into
practice. By describing the context and functional aspects of stakeholder groups,
like those working as community advisory boards (CABs), others can learn from
these experiences and operationalize their own CABs. Our objective is to describe
our experiences with diverse CABs affiliated with our community engagement group
within our institution's Clinical Translational Sciences Award (CTSA). We
identify key contextual elements that are important to administering CABs.
METHODS: A group of investigators, staff, and community members engaged in a 6
month collaboration to describe their experiences of working with six research
CABs. We identified the key contextual domains that illustrate how CABS are
developed and sustained. Two lead authors, with experience with CABs and
identifying contextual domains in other work, led a team of 13 through the
process. Additionally, we devised a list of key tips to consider when devising
CABs. RESULTS: The final domains include (1) aligned missions among stakeholders
(2) resources/support, (3) defined operational processes/shared power, (4) well
described member roles, and (5) understanding and mitigating challenges. The tips
are a set of actions that support the domains. CONCLUSIONS: Identifying key
contextual domains was relatively easy, despite differences in the respective
CAB's condition of focus, overall mission, or patient demographics represented.
By contextualizing these five domains, other research and community partners can
take an informed approach to move forward with CAB planning and engaged research.
PMID- 29332851
TI - Empirically Derived Lessons Learned about What Makes Peer-Led Exercise Groups
Flourish.
AB - BACKGROUND: Physical exercise confers many health benefits, but it is difficult
to motivate people to exercise. Although community exercise groups may facilitate
initiation and persistence in an exercise program, reports regarding factors that
allow such groups to flourish are limited. OBJECTIVES: We performed a prospective
qualitative evaluation of our experience starting a program of community-based,
peer-led exercise groups for military veterans to identify important lessons
learned. METHODS: We synthesized data from structured observations, post
observation debriefings, and focus groups. Our participants were trained peer
leaders and exercise group members. Our main outcomes consisted of empirically
derived lessons learned during the implementation of a peer-led group exercise
program for veterans at multiple community sites. We collected and analyzed data
from 40 observation visits (covering 14 sites), 7 transcribed debriefings, and 5
focus groups. RESULTS: We identified five lessons learned. (1) The camaraderie
and social aspect of the exercise groups provided motivation for people to stay
involved. (2) Shared responsibility and commitment to each other by the group
members was instrumental to success. (3) Regular meeting times encouraged
participation. (4) Variety, especially getting outdoors, was very popular for
some groups. (5) Modest involvement of professionals encouraged ongoing
engagement with the program. CONCLUSIONS: Both social and programmatic issues
influence implementation of group exercise programs for older, predominantly
male, veterans. These results should be confirmed in other settings.
PMID- 29332852
TI - How Co-Developed Are Community and Academic Partnerships?
AB - BACKGROUND: The world-renowned resources of Johns Hopkins Hospital (JHH) in
Baltimore, Maryland, stand in marked contrast with the surrounding impoverished
neighborhoods. Community-based organizations (CBOs) are critical frontline
responders to residents' needs. Baltimore CONNECT, an academic-community
partnership, co-developed an intervention to strengthen connections between CBOs
and between CBOs and the health care system. OBJECTIVES: To understand how
members of an academic- community partnership define the act of "co-development"
and share perceptions of barriers, facilitators, and ways to measure it. METHODS:
We conducted semistructured interviews with 15 community partners, academic
partners, and external stakeholders. RESULTS: Partners conceptualized co
development as a fluid and evolving process that is the outcome of shared
decision making. This exploration revealed nuances within partnership dynamics,
including motivations for participation, underlying incentives, partnership
equality, balance of power, and trust and relation building. CONCLUSIONS: We
present insights that can be used by academic researchers and community leaders
looking to co-develop interventions to improve health in urban communities
domestically and internationally.JHH in Baltimore, Maryland, is one of the most
highly regarded hospitals in the United States. However, its institutional
resources stand in marked contrast with those available to the impoverished
neighborhoods that surround it. Many have called for JHH to play a greater role
in the surrounding community, where it serves as a leading source of health care.
PMID- 29332854
TI - The Development of a Postpartum Weight Management Intervention for Low-Income
Women: End-User Perspectives as Groundwork.
AB - BACKGROUND: Postpartum weight retention (PPWR) leads to increased rates of
maternal and childhood obesity, especially among low-income families. Literature
is sparse regarding interventions to address PPWR. OBJECTIVE: To gain practical
insight into low-income women's preferences and opinions regarding PPWR
management at a community-based organization (CBO). METHODS: Mixed female focus
groups composed of CBO staff and clients (n = 17) were asked open-ended questions
about PPWR and potential intervention components. Systematic analysis of the
discussions was performed to identify overarching themes. CONCLUSIONS: The tenets
of community-engaged research state the necessity of developing community-based
interventions with initial input and partnership with the potential end-users. In
this study, low-income women were eager to share their thoughts about the
postpartum period and potential solutions to correct unhealthy weight, thus
completing a critical step in intervention development. The majority of women
wanted to manage their weight in the postpartum setting, but needed structure,
social support, assurance they would not injure themselves or their babies, and
time saving strategies to do so.
PMID- 29332853
TI - Implementing the Chronic Care Model for Opioid and Alcohol Use Disorders in
Primary Care.
AB - BACKGROUND: Effective treatments for opioid and alcohol use disorders (OAUD) are
available, yet only a small percentage of those needing treatment receive it.
OBJECTIVES: This paper describes a collaborative planning and development process
used by researchers and community providers to apply the chronic care model to
the delivery of treatment for OAUD in primary care. The goal was to develop and
implement an intervention that would support the delivery of brief psychotherapy
and medication-assisted treatment (MAT). METHODS: We used focus groups and
interviews to identify barriers and facilitators, and organized the results using
the chronic care model. We then identified implementation strategies, the
intended organizational changes, and the materials necessary to carry out each
strategy, and pilot-tested the process. RESULTS AND CONCLUSIONS: We describe the
methods and outcomes of the collaborative planning and development process, and
discuss implications of the work for the integration of substance use treatment
with primary care.
PMID- 29332855
TI - Yeego Gardening! A Community Garden Intervention to Promote Health on the Navajo
Nation.
AB - BACKGROUND: Yeego Gardening! is a community garden intervention to increase
gardening behavior, increase access to low-cost fruit and vegetables, and
ultimately increase consumption in Navajo communities. OBJECTIVES: To design a
theory-based, culturally relevant intervention with three components: a community
garden, monthly workshops on gardening and healthy eating, and community
outreach. METHODS: Gardens were constructed and maintained in collaboration with
community-based organizations in two Navajo communities. Monthly workshops were
held throughout the growing season and incorporated aspects of Navajo culture and
opportunities to build confidence and skills in gardening and healthy eating
behaviors. In addition, program staff attended community events to promote
gardening and healthy eating. CONCLUSIONS: Community input was essential
throughout the planning and implementation of the intervention. If effective,
community gardens may be a way to increase fruit and vegetable availability and
intake, and ultimately reduce risk of obesity and diabetes.
PMID- 29332856
TI - Transform Health Arkansas: A Transgender-Led Partnership Engaging Transgender/Non
Binary Arkansans in Defining Health Research Priorities.
AB - BACKGROUND: Transgender/non-binary (trans/NB) individuals face major challenges,
including within health care. OBJECTIVES: Transform Health Arkansas (THA) engaged
trans/ NB Arkansans in defining their greatest health-related concerns to inform
responsive, partnered, participatory research. METHODS: The THA partnership
engaged trans/NB individuals through an interactive, trans/NB-led process in nine
summits across the state and collected surveys on research interests. Descriptive
analysis examined respondent characteristics by gender identity, mode of survey
completion, and most pressing concerns. RESULTS: The summits, attended by 54
trans/NB and 29 cisgender individuals, received positive evaluations. The top
five priorities among 140 survey respondents included (1) transition-related
insurance coverage, (2) access to transition care, (3) education of health care
providers, (4) public education, and (5) supportive health care systems. The THA
has also led to trans/NB individuals educating a range of audiences about
transgender issues. CONCLUSIONS: Next steps include dissemination, identification
of evidence-based interventions addressing prioritized issues, and joint
development of a research agenda.
PMID- 29332857
TI - Food Policy Council Case Study Describing Cross-sector Collaboration for Food
System Change in a Rural Setting.
AB - PROBLEM: Food Policy Councils (FPCs) are cross-sector collaborations that bring
representatives from across the food system together to identify issues,
coordinate programs, and inform policy. Little is known about how rural FPCs
operate to influence food access in their communities. PURPOSE: To explore how a
rural FPC facilitates cross-sector partnerships and influences food system change
through interviews with eight members of the Adam's County FPC. RESULTS:
Connections developed through the FPC helped council members work more
effectively in their home organizations. Four themes were discussed: council
dynamics and structure; sharing resources, expertise, and information; promoting
healthy food access through programs; and food policy opportunities and
challenges. CONCLUSIONS: This case study illustrates connections between FPC
members in a rural county and identifies how FPCs can facilitate food system
change in their communities. Improving our understanding of how rural FPCs
function can help to advance the potential public health impact of councils.
PMID- 29332858
TI - The effect of thiamine and its metabolites on peripheral neuropathic pain induced
by cisplatin in rats.
AB - Thiamine pyrophosphate (TPP) is the active metabolite of thiamine. This study
aimed to investigate the effects of thiamine and TPP on cisplatin-induced
peripheral neuropathic pain (PNP). Male albino Wistar type Rattus norvegicus were
divided into six groups (n=6) that received 2 mg/kg cisplatin (CIS), 25 mg/kg
thiamine (TM), 2 mg/kg cisplatin+25 mg/kg thiamine (CTM), 25 mg/kg TPP (TPP), 2
mg/kg cisplatin+25 mg/kg TPP (CTPP), or distilled water (healthy group; HG) for 8
days intraperitoneally. Analgesic effect was measured with a Basile Algesimeter.
IL-1beta, malondialdehyde (MDA), total glutathione (tGSH), thiamine, and TPP were
determined in blood samples. Histopathological examinations were performed on
removed sciatic nerves. The percent analgesic effects of the CTM and CTPP groups
were calculated to be 21.3% and 82.9%, respectively. Increased production of IL
1beta and MDA by cisplatin was inhibited by TPP, while it was not inhibited by
thiamine. Conversion of thiamine to TPP significantly decreased in the CIS group.
Histopathological and biochemical investigations demonstrated that hyperalgesia
and sciatic nerve damage developed in the CIS and CTM groups with low TPP levels.
These results indicate that cisplatin inhibits the formation of TPP from
thiamine, leading to severe PNP. This finding suggests that TPP may be more
beneficial than thiamine for the treatment of cisplatin-induced PNP.
PMID- 29332859
TI - Grading fatty liver by ultrasound time-domain radiofrequency signal analysis: an
in vivo study of rats.
AB - This study aimed to assess the severity of fatty liver (FL) by analyzing
ultrasound radiofrequency (RF) signals in rats. One hundred and twenty rats (72
in the FL group and 48 in the control group) were used for this purpose.
Histological results were the golden standard: 42 cases had normal livers (N), 30
cases had mild FL (L1), 25 cases had moderate FL (L2), 13 cases presented with
severe FL (L3), and 10 cases were excluded from the study. Four RF parameters
(Mean, Mean/SD ratio [MSR], skewness [SK], and kurtosis [KU] were extracted.
Univariate analysis, spearman correlation analysis, and stepwise regression
analysis were used to select the most powerful predictors. Receiver operating
characteristic (ROC) analysis was used to compare the diagnostic efficacy of
single indexes with a combined index (Y) expressed by a regression equation.
Mean, MSR, SK, and KU were significantly correlated with FL grades (r=0.71,
P<0.001; r=0.81, P<0.001; r=-0.79, P<0.001; and r=-0.74, P<0.001). The regression
equation was Y=-4.48 + 3.20 * 10-2X1 + 3.15X2 (P<0.001), where Y=hepatic
steatosis grade, X1 =Mean, and X2 =MSR. ROC analysis showed that the curve areas
of the combined index (Y) were superior to simple indexes (Mean, MSR, SK, and KU)
in evaluating hepatic steatosis grade, and they were 0.95 (L>=L1), 0.98 (L>=L2),
and 0.99 (L>=L3). Ultrasound radiofrequency signal quantitative technology was a
new, noninvasive, and promising sonography-based approach for the assessment of
FL.
PMID- 29332860
TI - Impact of the Great East Japan Earthquake on Body Mass Index, Weight, and Height
of Infants and Toddlers: An Infant Survey.
AB - BACKGROUND: The body mass index (BMI) of preschool children from 4 years of age
through primary school has increased since the Great East Japan Earthquake, but
that of children aged under 3 years has not been studied. This study evaluated
how the anthropometrics of younger children changed following the earthquake.
METHODS: Height and weight data of children living in northeast Japan were
collected from 3-, 6-, 18-, and 42-month child health examinations. We compared
the changes in BMI, weight, and height among infants affected by the earthquake
between their 3- and 6-month health examinations, toddlers affected at 21-30
months of age (affected groups), and children who experienced the earthquake
after their 42-month child health examination (unaffected group). A multilevel
model was used to calculate the BMI at corresponding ages and to adjust for the
actual age at the 3-month health examination, health examination interval, and
gestational age. RESULTS: We recruited 8,479 boys and 8,218 girls living in
Fukushima, Miyagi, and Iwate Prefectures. In the infants affected between their 3
and 6-month health examinations in Fukushima, the change in BMI at 42 months of
age was greater than among the unaffected children. In the toddlers affected at
21-30 months of age in Fukushima, the change in BMI was greater, but changes in
weight and height were less. CONCLUSIONS: Affected infants and toddlers in
Fukushima suggested some growth disturbances and early adiposity rebound, which
can cause obesity. The future growth of children affected by disasters should be
followed carefully.
PMID- 29332861
TI - Epicardial Fat Thickness and Bone Mineral Content: The Healthy Twin Study in
Korea.
AB - BACKGROUND: The conventional concept of positive association between general
obesity and bone health was challenged in recent studies reporting the different
effects of specific fat deposition on bone health. In the present study, we
investigated the association between epicardial fat and bone health. METHODS: We
measured echocardiographic epicardial fat thickness (EFT) and bone mineral
content (BMC) in a twin-family cohort of Koreans (n = 1,198; 525 men, 460 pre-
and 213 post-menopausal women). A total 121 pairs of monozygotic twin (MZ) and
404 pairs of dizygotic twin and sibling pairs (DZ/Sib) were included. RESULTS:
EFT was positively associated with BMC in total, as well as in three subgroups
(beta = 0.107, 0.076, and 0.058 for men, pre-, and post-menopausal women,
respectively). The positive association between EFT and BMC remained for DZ/Sib
difference analysis, but was absent for MZ comparisons. The positive association
between BMI and BMC was consistent for DZ/Sib and MZ difference analysis. After
adjusting for the effect of general obesity via BMI, the association between BMC
and EFT was statistically non-significant (beta = 0.020, 0.000, and -0.009 for
men, pre-, and post-menopausal women, respectively). CONCLUSION: Our findings do
not support epicardial fat's beneficial effects on bone health, whereas general
adiposity has an osteotropic effect. The association between EFT and BMC is
through common genetic component factors.
PMID- 29332862
TI - Using relaxation techniques to improve sleep during naps.
AB - Insufficient sleep is a common occurrence in occupational settings (e.g. doctors,
drivers, soldiers). The resulting sleep debt can lead to daytime sleepiness,
fatigue, mood disorder, and cognitive deficits as well as altered vascular,
immune and inflammatory responses. Short daytime naps have been shown to be
effective at counteracting negative outcomes related to sleep debt with positive
effects on daytime sleepiness and performance after a normal or restricted night
of sleep in laboratory settings. However, the environmental settings in the
workplace and the emotional state of workers are generally not conducive to
beneficial effects. Here, we tested whether relaxation techniques (RT) involving
hypnosis might increase total sleep time (TST) and/or deepen sleep. In this
study, eleven volunteers (aged 37-52) took six early-afternoon naps (30 min) in
their occupational workplace, under two different conditions: control 'Naps' or
'Naps + RT' with a within-subjects design. Our results demonstrate that adding RT
to naps changes sleep architecture, with a significant increase in the TST,
mostly due to N2 sleep stage (and N3, to a lesser extent). Therefore, the
deepening of short naps with RT involving hypnosis might be a successful non
pharmacological way to extend sleep duration and to deepen sleep in occupational
settings.
PMID- 29332863
TI - Lipid Parameters are Independently Associated with Cardio-Ankle Vascular Index
(CAVI) in Healthy Japanese Subjects.
AB - AIM: To investigate the associations of conventional lipid parameters with
arterial stiffness assessed by cardio-ankle vascular index (CAVI). METHODS: A
retrospective cross-sectional study was conducted in 23,257 healthy Japanese
subjects (12,729 men and 10,528 women, aged 47.1+/-12.5 years, body mass index
(BMI) 22.9+/-3.4 kg/m2) who underwent health screening between 2004 and 2006 in
Japan. RESULTS: Male subjects had significantly higher BMI, CAVI and
triglycerides (TG), and lower high-density lipoprotein cholesterol (HDL-C)
compared to female subjects. After adjusting for confounders, including gender,
age, systolic blood pressure and BMI identified by multiple regression analysis,
adjusted CAVI was lower in normolipidemic than in dyslipidemic subjects. Among
dyslipidemic subjects, those with hypertriglyceridemia had higher adjusted CAVI.
A trend test detected linear relations between adjusted CAVI and all the
conventional lipid parameters throughout the entire range of serum levels. After
adjusting for confounders, logistic regression models showed that all lipid
parameters contributed independently to high CAVI (>=90th percentile). Receiver
operating-characteristic analysis determined reliable cut-off values of 93 mg/dl
for TG (area under the curve, AUC= 0.735), 114 mg/dl for low-density lipoprotein
cholesterol (AUC=0.614) and 63 mg/dl for HDL-C (AUC=0.728) in predicting high
CAVI. These cut-off values were confirmed to independently predict high CAVI in a
bivariate logistic regression model. CONCLUSION: The present study demonstrated
independent contribution of conventional lipid parameters to CAVI, indicating a
possible association of lipid parameters with early vascular damage.
PMID- 29332864
TI - Associations of periparturient plasma biochemical parameters, endometrial
leukocyte esterase and myeloperoxidase, and bacterial detection with clinical and
subclinical endometritis in postpartum dairy cows.
AB - This study was aimed at demonstrating associations between peripheral biochemical
parameters, endometrial leukocyte esterase (LE) and myeloperoxidase (MPO), and
bacterial detection with the degree of endometrial inflammation, and determining
the best time postpartum for diagnosing endometritis to predict subsequent
fertility in dairy cows. Plasma albumin, blood urea nitrogen (BUN), total
cholesterol (T-cho), NEFA, and BHBA concentrations were analyzed in 43 Holstein
cows at 3, 5 and 7 weeks postpartum (W3, W5 and W7). Endometrial samples were
collected at W3, W5 and W7 to examine LE and MPO activities, bacterial detection
rates, and PMN% profiles. The 43 cows were divided into healthy (HE), subclinical
endometritis (SE), and clinical endometritis (CE) groups, classified differently
at W3, W5 and W7 based on the definitions of SE and CE for each of the three
weeks pp. LE level had an association with PMN% in all weeks pp (P<0.05). Albumin
and BUN levels had weak negative associations with endometrial PMN% at W3.
Pathogenic bacterial detection rates were higher in the cows with endometritis at
W3 and W5. Conception rate at first artificial insemination tended to be lower
(P=0.057) in the cows diagnosed with endometritis at W3 than in the healthy cows.
In conclusion, associations were found between endometrial LE and endometritis,
but not for MPO and endometritis. Diagnosing endometritis in W3 may be the best
moment to predict subsequent fertility.
PMID- 29332866
TI - Impact of Stent Type on the Long-Term Prognosis of Patients With Vasospastic
Angina - Can We Judge a Stent Just by Its Cover?
PMID- 29332865
TI - Fibrillar architecture at three different sites of the bovine superficial digital
flexor tendon.
AB - Superficial digital flexor tendon (SDFT) of the bovine hindlimb originates from
the caudolateral aspect of the distal femur and finally inserts onto the plantar
aspect of the middle phalanges. In the present study, morphology and morphometry
of the bovine SDFT at the muscle-tendon junction (MTJ), middle metatarsus (mM)
and tendon-bone interface (TBI) were investigated. Cross-sectional morphology at
the three regions of SDFT were oval, semioval and ring-formed, respectively.
Significant difference in cross-sectional area was found only between MTJ-mM and
mM-TBI (P<0.05). Functional compression and friction from the adjacent structures
could be the most potential interactions affecting such appearances. Morphometric
data of tenocyte number, water content, and glycosaminoglycan (GAG) length and
angle were found increasing in the proximodistal direction, except the fibril
diameter and collagen fibril index (CFI). Statistical analyzes could reveal
significant differences in average number of tenocytes (P<0.0001), CFI (between
MTJ-mM and MTJ-TBI, P<0.05), water content (between MTJ-TBI, P<0.05), length of
GAG chains (between MTJ-TBI, P<0.05), and angle of GAG chains (P<0.0001),
respectively. The fibrillar characteristics at the three different areas,
including fibril diameter distribution and interfibrillar distance, existed in
conforming to the tensional axes in situ. In addition, length and angle of GAG
chains were relevant to moving directions of the collagen fibrils.
PMID- 29332867
TI - ?
PMID- 29332868
TI - [Azacitidine treatment for acute myeloid leukemia with myelodysplasia-related
changes during peritoneal dialysis].
AB - Azacitidine (AZA) is useful for the treatment of myelodysplastic syndrome;
however, there are a few case reports involving patients receiving hemodialysis
and no case reports involving patients receiving peritoneal dialysis. We describe
a patient with acute myeloid leukemia with myelodysplasia-related changes (AML
MRC) receiving peritoneal dialysis who was treated with AZA. Peritoneal dialysis
was initiated for an 85-year-old man with chronic renal failure in April 2014. In
February 2015, peripheral blood analysis showed pancytopenia and bone marrow
examination revealed excess of myeloblasts and dysplasia of trilineage cells. He
was diagnosed with AML-MRC and treated with AZA because of being elderly and
suffering from chronic renal failure. He achieved transfusion independence after
1 course and hematological remission after 3 courses of AZA treatment, without
severe side effects. This case suggests that AZA is an effective therapeutic
option for patients with AML-MRC receiving peritoneal dialysis.
PMID- 29332869
TI - [Disseminated fusariosis in patients with acute leukemia: a retrospective
analysis of three cases].
AB - We report three cases of fusariosis that occurred during the treatment of acute
leukemia, during the past 5 years at our institution. Case 1: A 70-year-old male
with relapsed and refractory acute lymphoblastic leukemia (ALL) developed fever
and multiple nodular lesions in both the lungs. Blood culture that was
subsequently obtained revealed Fusarium species. Treatment with liposomal
amphotericin B (L-AMB) was ineffective, and the condition of the patient
deteriorated rapidly leading to death. Case 2: A 28-year-old male with T-ALL
developed echthyma gangrenosum (EG) ulcers on the scrotum during conditioning for
transplantation. Antifungal therapy with L-AMB was ineffective, and later,
itraconazole and micafungin (MCFG) were introduced. However, the engraftment was
not achieved, and the patient died on day 27. Microbiological examination of EG
samples collected on day 13 revealed infection by Fusarium species post mortem.
Case 3: A 50-year-old male with blast crisis of chronic myeloid leukemia
developed EG primarily on the trunk during chemotherapy. The patient died without
any response to L-AMB and MCFG. A culture obtained from EG on day 19 yielded
Fusarium species, post mortem. The prognosis of fusariosis is extremely poor.
However, skin lesions such as EG may assist in the early diagnosis of the
disseminated disease.
PMID- 29332871
TI - [Successful treatment of secondary graft failure with donor lymphocyte infusion
in a post-allogeneic stem cell transplant acute myeloid leukemia patient].
AB - Here we report a case of secondary graft failure that was effectively treated
with donor lymphocyte infusion (DLI). A 64-year-old female patient with acute
myeloid leukemia obtained partial remission with azacitidine therapy and
subsequently underwent unrelated allogeneic bone marrow transplantation (BMT).
After confirming successful engraftment and achieving complete remission with
incomplete blood count recovery, she was subsequently followed up at an
outpatient clinic. A routine test performed by day 110 after BMT revealed the
presence of pancytopenia. A bone marrow aspirate did not reveal any evidence of
disease relapse or hemophagocytic syndrome but demonstrated hematopoietic
insufficiency. Donor chimerism also declined over time; thus, the patient was
diagnosed with secondary graft failure. Supportive treatment, including
granulocyte-colony stimulating factor and blood transfusion, failed to improve
the blood parameters. Because the patient refused a second BMT, we performed DLI
on day 147 after BMT (CD3+ cells: 1.0*107/kg, single dose). Consequently, the
blood cell count improved promptly and dramatically without adverse events.
Following this, we discussed the case and analyzed the related literature.
PMID- 29332870
TI - [Autologous peripheral blood stem cell transplantation for double-refractory
myeloma with K-RAS and N-RAS mutations].
AB - The prognosis of multiple myeloma (MM) has been improved due to the introduction
of novel agents like proteasome inhibitors and immunomodulatory drugs (IMiDs).
However, some cases are refractory to the use of novel agents, and the prognosis
of such cases is poor. A 53-year-old male was diagnosed with MM and categorized
as follows: Bence-Jones protein lambda type MM, Durie-Salmon IIIA, international
staging system (ISS) stage II, and revised ISS stage II. Mutations in K-RAS and
IGH/FGFR3 translocation were detected at diagnosis. His tumor was refractory to
seven therapeutic regimens including bortezomib, IMiDs (lenalidomide,
thalidomide, pomalidomide), conventional chemotherapy, and radiation therapy. N
RAS mutations, CKS1B gains, and C-MYC split signals were detected after
treatment. We performed high-dose melphalan/autologous stem cell transplantation
(HD-MEL/ASCT) as a salvage therapy and achieved very good partial response. The
correlation between K-RAS mutations and poor prognosis or between N-RAS mutations
and reduced sensitivity to bortezomib is reported. However, RAS mutations are
reported as a favorable factor for HD-MEL/ASCT. In general, mutations of both the
K-RAS and N-RAS are known to be mutually exclusive. This rare MM case has
mutations in both K-RAS and N-RAS, and the possible relevance of these mutations
to both the refractoriness to novel therapies and sensitivity to HD-MEL/ASCT is
suggested.
PMID- 29332872
TI - [Successful treatment of large granular lymphocytic leukemia accompanied by
refractory anemia with alemtuzumab].
AB - A 39-year-old man with anemia presented at our hospital in November 2011.
Peripheral blood analysis revealed lymphocytosis with a large granular lymphocyte
(LGL) count of 2,272/ul, with CD3+, CD4-, CD8+, CD56-, TCR-alphabeta+; Southern
blotting analysis revealed clonal TCR Cbeta 1 gene rearrangement, leading to the
diagnosis of T-LGL leukemia. In June 2012, the patient was administered with
cyclophosphamide as an initial treatment because he developed transfusion
dependent anemia. His anemia improved, and the treatment was discontinued in
March 2013. However, anemia recurred in March 2014. The administration of
cyclophosphamide was resumed; however, it was subsequently replaced with
cyclosporine because of the risk of secondary cancer due to the long-term use of
cyclophosphamide. However, his anemia did not improve. Further, the patient was
administered with prednisone, methotrexate, and pentostatin; however, the
transfusion-dependent state persisted with the cumulative transfusion of 186 RBC
units until March 2016. After CD52 expression on the surface of LGL cells was
confirmed, treatment with alemtuzumab, which is a monoclonal antibody against
CD52, was initiated in April 2016 and the dose was gradually increased from 3 mg
to 30 mg thrice per week. The patient's anemia began to improve 1 week after
initiating alemtuzumab treatment, and he became transfusion-independent in the
second week. Although alemtuzumab treatment was discontinued at the fifth week on
the basis of a positive test result for CMV antigenemia, the result consequently
became negative after ganciclovir treatment. To date, the patient's hemoglobin
level has been maintained at approximately 12 g/dl without any treatment. Herein
we reported the case of a patient having LGL leukemia with refractory anemia that
was successfully treated using alemtuzumab.
PMID- 29332873
TI - [Durable remission attained by long-term brentuximab vedotin administration in a
relapsed post-allogeneic bone marrow transplant Hodgkin lymphoma patient].
AB - The prognosis for relapsed Hodgkin lymphoma after allogeneic hematopoietic cell
transplantation (HSCT) is poor, partly because of limited treatment options. Here
we present a case of a Hodgkin lymphoma patient who relapsed after allogeneic
HSCT but remains in complete remission (CR) at 38 months from the start of
extended brentuximab vedotin (BV) dosing. A 33-year-old man with refractory and
relapsed nodular sclerosis classical Hodgkin lymphoma who underwent previous
treatments, including adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD)
; seven combination regimens; and autologous HSCT, prior to allogeneic HSCT
achieved CR after three cycles of BV. BV was continued for 26 cycles and then
discontinued because of a neurogenic bladder. The other adverse effects were mild
paresthesia in the fingers, mild dysgeusia, and fatigue. The patient still
remains in CR at 38 months from the start of BV. Thus, extended BV dosing may be
a treatment option for relapsed and refractory Hodgkin lymphoma after allogeneic
HSCT.
PMID- 29332874
TI - [Myelodysplastic syndrome with refractory hemorrhage due to reduced platelet
aggregation activity].
AB - A 75-year-old woman suffered a cat bite 10 months after myelodysplastic syndrome
(MDS) diagnosis. She visited our hospital because the internal bleeding of the
wound did not improve. Although the wound was treated, the bleeding did not stop.
She was hospitalized for emergency medical treatment because the bleeding volume
exceeded 200 ml. Although her platelet count was normal, the platelet function
test showed a decrease in collagen and arachidonic acid aggregation. After
platelet transfusion, her bleeding stopped. Patients with MDS may potentially
have platelet dysfunction. In the case of bleeding without thrombocytopenia, a
platelet function test should be performed and treatment intervention, such as
platelet transfusion, should be considered.
PMID- 29332875
TI - [Recurrent multiple lung lesions synchronizing with the disease activity of
multiple myeloma].
AB - A 68-year-old male patient, who was diagnosed with MGUS (IgG-lambda) 11 years
ago, was referred to our hospital because of a progressing pancytopenia. He was
diagnosed with multiple myeloma (MM) and was hospitalized because of fever and
pneumonia. Although empiric antibiotic and antifungal therapies were promptly
initiated, his pneumonia worsened. Chest CT images revealed diffuse interstitial
pneumonia. Although bortezomib/dexamethasone therapy was initiated as a treatment
for MM and pneumonia, he showed little response. His pneumonia worsened and
progressed to acute respiratory distress syndrome. Using mPSL (500 mg/day),
sivelestat, and MM treatment switching to lenalidomide/dexamethasone (Rd), his
respiratory status and CT findings rapidly improved. He received Rd therapy as an
outpatient; however, after the completion of six cycles of therapy, his MM
progressed, with a recurrence of pneumonia and high fever again. The onset of
pneumonia was closely associated with MM progression. His pneumonia improved by
treatment with mPSL half-pulse and MM treatment switching to carfilzomib/Rd. In
the present study, we report the case of a patient with myeloma, who presented
with multiple interstitial pneumonia, resulting in respiratory failure twice in
concordance with myeloma progression.
PMID- 29332876
TI - [Primary breast diffuse large B-cell lymphoma developing subsequent to
estramustine therapy for prostate cancer].
AB - An 85-year-old male presented with 1-year history of a right breast mass. Needle
biopsy of the mass revealed diffuse proliferation of large lymphoid cells that
were positive for CD20, BCL2, BCL6, and MUM1 and negative for CD5, CD10, MYC, and
EBER. The patient was diagnosed as having diffuse large B-cell lymphoma, a type
of primary breast lymphoma (PBL). Sex hormone imbalance, which causes conditions
such as gynecomastia, is associated with PBL development in males. Estramustine
is a nitrogen mustard moiety linked to estradiol. For 5 years, the patient
underwent estramustine therapy for treating prostate cancer. Our case suggests an
important role of estrogen in PBL development.
PMID- 29332877
TI - [Overview].
PMID- 29332878
TI - [Impact of HLA mismatch on transplant outcomes].
AB - Human leukocyte antigen (HLA) mismatch increases the risk of severe graft-versus
host disease (GVHD) and transplant-related mortality. However, the variety of
stem cell sources such as cord blood units or the improvements in GVHD
prophylaxis makes the interpretation of HLA mismatch more complex. In unrelated
transplantation, the locus of HLA mismatch has a great impact on the donor
candidate selection, whereas in related transplantation, it has an impact on the
intensity of GVHD prophylaxis because donor availability is limited. Anti
thymocyte globulin and post-transplant cyclophosphamide are attractive GVHD
prophylactic agents to reduce the risk of immune-associated complications in HLA
mismatched transplantations. HLA mismatch has a reduced impact in adult cord
blood transplantation. In this review article, the impact of HLA mismatch based
on graft sources is discussed.
PMID- 29332879
TI - [Progresses in pretransplant conditioning strategies].
AB - Reduction of pretransplant conditioning intensity since the late 1990s has
resulted in an increased incidence of relapse, although the number of
transplantations has dramatically increased. In the 2000s, pretransplant
conditioning was intensified again using drugs with less non-hematological
toxicity. For myeloid malignancies, intravenous busulfan (ivBu), which has lesser
toxicity than its oral formulation, was introduced. Its myeloablative dose can be
safely administered to many patients, including the elderly. Fludarabine-ivBu
combination is reported to be comparable or even better than conventional
myeloablative conditioning regimens, such as Bu-Cy or TBI-Cy, for those 50 years
and older. The cumulative incidence of early NRM post-transplant in patients in
remission was more or less comparable to those undergoing the Seattle regimen
consisting of Flu+TBI 2 Gy. Incorporating novel drugs into conditioning regimens
may further reduce toxicity, particularly for patients not in remission.
PMID- 29332880
TI - [Impact of genetic polymorphisms on post-transplant complications].
AB - Genetic association studies are now widely applied to various medical conditions
and abnormalities. Unfortunately, it remains challenging to conduct such studies
in cases that require hematopoietic stem cell transplantation (HSCT) because
candidate patients usually have a complicated clinical background. In this field,
a uniform cohort and well-designed protocol are critical to increasing the
effectiveness of genetic association analyses, and parameters such as pre
conditioning regimen, donor source, graft versus host disease and its
prophylaxis, and disease status need to be considered. Our studies thus far have
revealed that focusing on the relationship between drug metabolism-associated
genes and drug-induced complications after HSCT could often offset the
complicated clinical background. Thus, here we describe a genetic association
study focused on complications after HSCT.
PMID- 29332881
TI - [Mesenchymal stem cells for treatment of graft-versus-host disease].
AB - Steroid-refractory graft-versus-host disease (SR-GVHD) is one of the most
important complication post allogeneic hematopoietic stem cell transplantation.
Mesenchymal stem cells (MSCs) possess characteristic immunomodulatory features
which are beneficial in the salvage treatment for SR-GVHD. Following the first
case report in 2004, numerous clinical trials have shown encouraging results with
MSC infusions for treating SR-GVHD. In Japan, two clinical trials have achieved
favorable results, and subsequently in September 2015, MSC infusion became the
first approved allogeneic cell therapy for SR-GVHD. Currently, MSCs are available
at limited institutes, and all patients infused with MSCs have been registered in
the post marketing survey. Based on the results of this survey, the establishment
of guidelines for the proper use of MSCs is anticipated. Moreover, several groups
have reported the efficacy of MSCs for chronic GVHD or GVHD prophylaxis. In the
present review, current issues regarding the use of MSCs in the management of
GVHD are summarized.
PMID- 29332883
TI - ?
PMID- 29332882
TI - [Role of long-term follow-up in management of late-onset post-hematopoietic stem
cell transplant complications].
AB - As the number of long-term survivors after allogeneic hematopoietic stem cell
transplantation (HSCT) has increased owing to advances in transplantation and
supportive care techniques, the health and welfare of these survivors have come
into focus. However, they are still at risks for various complications, including
chronic graft-versus-host disease, infectious diseases, and secondary cancers
even in the late period, which can not only interfere with the patient's quality
of life (QOL) but also lead to death. The importance of long-term follow-up
(LTFU) and management have been recently recognized, and nationwide systems to
promote LTFU care in patients receiving HSCT, such as medical fee revision,
publication of a LTFU guideline unique to Japan, and preparation of patient
pocketbook, is under consideration. The number of medical facilities at LTFU
outpatient clinic is also increasing; therefore, an optimal comprehensive support
system may be established sooner or later. However, self-management by patients
is essential to overcome late complications as well as to improve QOL after HSCT.
Healthcare professionals should collaborate and continue to make the greatest
possible efforts to educate patients regarding the risks of late complications
and their prevention.
PMID- 29332884
TI - ?
PMID- 29332885
TI - ?
PMID- 29332886
TI - Improved systemic delivery of insulin by condensed drug loading in a dimpled
suppository.
AB - The development of peptide therapeutics owing to the advances in biotechnology
has overcome some unmet medical needs; however, the route of administration is
still limited to injections. Systemic delivery of insulin via an enteral route
remains a great challenge due to its instability and low mucosal permeability. In
this study, we investigated the effect of drug condensation in a suppository on
the efficacy of insulin after rectal administration. Suppositories with dimples
are prepared by a mold method using a hard fat (Suppocire(r) AM). Insulin or
fluorescein isothiocyanate-dextran (molecular weight: 3,000-5,000) (FD4) as a
model of a hydrophilic macromolecule was loaded in the dimples, and sealed with
other lipids with different melting points. The in vitro release test showed that
the time to 50% drug release depends on the melting point of the lipid for
sealing but not on the number of dimples. The suppositories with one-, or three
dimple containing insulin and caprylocaproyl macrogol-8 glyceride (Labrasol(r))
were administered to rats at 0.5 U/head. The reduction in plasma glucose level
was more significant for the one-dimple-type suppository than for the three
dimple-type although the one-dimple-type suppository contained less amount of
Labrasol by one-third compared to the three-dimple-type. These results suggest
that condensation of an insulin dose in a limited surface area of a suppository
improves systemic availability via the rectal route with a reduced amount of an
absorption enhancer.
PMID- 29332887
TI - Both triazolyl ester of ketorolac (15K) and YM155 inhibit the embryonic
angiogenesis in ovo (fertilized eggs) via their common PAK1-survivin/VEGF
signaling pathway.
AB - 15 K is 1,2, 3-triazolyl ester of ketorolac, an old pain-killer, that blocks PAK1
by its R-form and inhibits COX-2 by its S-form. Mainly due to a robust increase
in cell-permeability, 15K is over 500 times more potent than ketorolac in both
anti-cancer and anti-PAK1 activities in cell culture with IC50 around 24 nM.
However, 15K has no anti-AKT activity. Angiogenesis requires at least the kinase
PAK1, and perhaps the kinase AKT as well, and is essential for a robust growth of
solid tumors. Thus, in this study, we examined the potential antiangiogenic
activity of 15K both in ovo and cell culture, prior to its in vivo (xenograft)
anti-cancer activity test. The IC50 of 15K against the embryonic angiogenesis in
ovo in CAM (chorioallantoic membrane) assay is around 1 nmol/egg. Surprizingly,
however, 15K failed to inhibit the tube formation of HUVECs (human umbilical vein
endothelial cells) in cell culture even at high as 150 MUM. In an attempt to
solve this mystery, we tested both in ovo as well as HUVECs-based anti-angiogenic
activity of a potent survivin-suppressor called YM155, which blocks PAK1, in
addition to AKT. YM155 is slightly more potent than 15K in CAM assay with IC50
around 0.5 nmol/egg, and apparenty inhibits the tube formation of HUVECs with
IC50 around 18 nM. According to a few previous findings with the direct PAK1
inhibitor frondoside A (FRA), the tube formation of HUVECs depends solely on
PAK1. Thus, the failure of 15K to affect their tube formation is most likely due
to their drug (15K)-resistance. Furthermore, unlike FRA, YM155 killed HUVECs with
IC50 around 18 nM, clearly indicating that AKT is essential for survival of
HUVECs, instead of their tube formation.
PMID- 29332888
TI - Potential of Piper betle extracts on inhibition of oral pathogens.
AB - In the present study, antimicrobial activity of Piper betle crude ethanol extract
against 4 strains of oral pathogens; Candida albicans DMST 8684, C. albicans DMST
5815, Streptococcus gordonii DMST 38731 and Streptococcus mutans DMST 18777 was
compared with other medicinal plants. P. betle showed the strongest antimicrobial
activity against all tested strains. Fractionated extracts of P. betle using
hexane, ethyl acetate, and ethanol, respectively, were subjected to antimicrobial
assay. The result revealed that the fractionated extract from ethyl acetate (F
EtOAc) possessed the strongest antimicrobial activity against all tested strains.
Its inhibition zones against those pathogens were 23.00 +/- 0.00, 24.33 +/- 0.58,
12.50 +/- 0.70 and 11.00 +/- 0.00 mm, respectively and its minimum inhibitory
concentrations were 0.50, 1.00, 0.50 and 1.00 mg/mL, respectively. Interestingly,
the minimum concentration to completely kill those pathogens was the same for all
strains and found to be 2.00 mg/mL. Killing kinetic study revealed that the
activity of F-EtOAc was dose dependent. HPLC chromatograms of P. betle extracts
were compared with its antimicrobial activity. An obvious peak at a retention
time of 4.11 min was found to be a major component of F-EtOAc whereas it was a
minor compound in the other extracts. This peak was considered to be an active
compound of P. betle as it was consistent with the antimicrobial activity of F
EtOAc, the most potential extract against the tested pathogens. It is suggested
that F-EtOAc is a promising extract of P. betle for inhibition of oral pathogens.
Separation and structure elucidation of the active compound of this extract will
be further investigated.
PMID- 29332889
TI - Effects of Caesalpinia sappan on pathogenic bacteria causing dental caries and
gingivitis.
AB - The present study explores antimicrobial activities of Caesalpinia sappan
extracts against three strains of oral pathogenic bacteria; Streptococcus mutans
DMST9567 (Smu9), Streptococcus mutans DMST41283 (Smu4), and Streptococcus
intermedius DMST42700 (Si). Ethanol crude extract of C. sappan (Cs-EtOH) was
firstly compared to that of other medicinal plants using disc diffusion method.
Cs-EtOH showed significantly higher effective inhibition against all tested
strains than other extracts and 0.12% chlorhexidine with the inhibition zone of
17.5 +/- 0.5, 18.5 +/- 0.0, and 17.0 +/- 0.0 mm against Smu9, Smu4, and Si,
respectively. Three fractionated extracts of C. sappan using hexane, ethyl
acetate, and ethanol, respectively, were further investigated. The fractionated
extract from ethanol (F-EtOH) presented the strongest activities with the minimum
bactericidal concentration (MBC) of 125-250 ug/mL. Killing kinetics of F-EtOH was
depended on the bacterial species and the concentration of F-EtOH. Two-fold MBC
of F-EtOH could kill all tested strains within 12 h whereas its 4-fold MBC showed
killing effect against Si within 6 h. Separation of F-EtOH by column
chromatography using chloroform/methanol mixture as an eluent yielded 11
fractions (F1-F11). The fingerprints of these fractions by high-performance
liquid chromatography at 280 nm revealed that F-EtOH consisted of at least 5
compounds. F6 possessed the significantly highest antimicrobial activity among 11
fractions, however less than F-EtOH. It is considered that F-EtOH is the
promising extract of C. sappan for inhibiting oral pathogenic bacteria and
appropriate as natural antiseptic for further develop of oral hygiene products.
PMID- 29332890
TI - In vitro oral epithelium cytotoxicity and in vivo inflammatory inducing effects
of anesthetic rice gel.
AB - In vitro cytotoxicity of lidocaine hydrochloride (LH) and prilocaine
hydrochloride (PH) to oral epithelial cells, isolated from tissue specimens of
healthy volunteers, were evaluated. Cell vitality after treating with 1-20%
anesthetic solutions for 5 and 30 min was investigated using F-actin and 4',6
diamidino-2-phenylindole staining technique and observed by fluorescence
microscopy. Vitality rate of more than 90% was found in all anesthetic groups at
both durations whereas no survived cell was found in a positive control group
(sodium dodecyl sulfate). Lactate dehydrogenase (LDH) assay was performed to
confirm the safety of both anesthetic solutions. Cell culture medium after
treating with LH or PH for 5 and 30 min were collected and analyzed using
commercial kits. The results showed no significant difference between the test
groups and negative control group (untreated culture) with low LDH levels. In
vivo inflammatory inducing effect of 5, 10, 20% LH or PH loaded rice gels was
investigated in healthy volunteers. Tumor necrosis factor alpha (TNF-alpha) in
gingival cervicular fluid was determined by ELISA technique. It was found that
the expression of TNF-alpha was not different from the baseline. The expression
of this inflammatory mediator caused by the commercial gel was higher than those
of both anesthetic rice gels. It might be due to the effects of other excipients
in the formulation of the commercial product. It is concluded that LH or PH
possess no cytotoxicity to oral epithelium and the developed rice gel base and LH
and PH rice gels do not induce inflammatory effect to oral tissues.
PMID- 29332891
TI - Protective effects of Phaseolus vulgaris lectin against viral infection in
Drosophila.
AB - Phytohemagglutinin (PHA) isolated from the family of Phaseolus vulgaris beans is
a promising agent against viral infection; however, it has not yet been
demonstrated in vivo. We herein investigated this issue using Drosophila as a
host. Adult flies were fed lectin approximately 12 h before they were subjected
to a systemic viral infection. After a fatal infection with Drosophila C virus,
death was delayed and survival was longer in flies fed PHA-P, a mixture of L4,
L3E1, and L2E2, than in control unfed flies. We then examined PHA-L4,
anticipating subunit L as the active form, and confirmed the protective effects
of this lectin at markedly lower concentrations than PHA-P. In both experiments,
lectin feeding reduced the viral load prior to the onset of fly death.
Furthermore, we found a dramatic increase in the levels of the mRNAs of
phagocytosis receptors in flies after feeding with PHA-L4 while a change in the
levels of the mRNAs of antimicrobial peptides was marginal. We concluded that P.
vulgaris PHA protects Drosophila against viral infection by augmenting the level
of host immunity.
PMID- 29332892
TI - Digital PCR for determination of cytochrome P450 2D6 and sulfotransferase 1A1
gene copy number variations.
AB - CYP2D6 and SULT1A1 occasionally show copy number variations (CNVs), with a larger
number generally indicating greater enzymic activity. However, those variations
are difficult to calculate using standard methods. With digital PCR, a recently
introduced method for CNV analysis, DNA molecules are subjected to limited
dilution and separated into nano-scale droplets prior to a PCR assay. Absolute
quantitation of copy number can then be performed with high accuracy and
sensitivity by determining the number of droplets showing an amplified signal for
the target gene. This is the first report of analyses of CYP2D6 and SULT1A1 CNVs
using a digital PCR method with blood sample from Japanese subject. Primers and
probes were synthesized for the target and reference genes, and copy number
calculation was performed using a QX200 Droplet Digital PCR System. Our results
showed that the copy numbers in CYP2D6*5 hetero, non-CNV, and CYP2D6xN subjects
were 1, 2, and 3 to 4, respectively. In addition, in non-CNV and multiplication
subjects, the number of copies for SULT1A1 was 2 and 3 to 6, respectively. We
found that the present digital PCR method was useful as well as accurate. In the
future, a combined genotyping, allele distinction, and copy number calculation
technique will be helpful for analysis of enzymic activity.
PMID- 29332893
TI - Do scleroderma patients look young?: Evaluation by using facial imaging system.
AB - These days various collagen supplements have widely been marketed. However, it
has not been scientifically proved whether increasing collagen can actually
prevent skin aging. Systemic sclerosis (SSc) is an autoimmune disease that is
characterized by thickening of the skin caused by accumulation of collagen. In
this study, we tried to evaluate facial skin characteristics and skin aging of
SSc patients by using digital imaging system. As the result, the severity of
wrinkles, texture and pores were significantly lower in SSc patients than control
subjects. Among them, wrinkles showed better correlation with skin thickness
score. Therefore, increased amount of collagen in scleroderma skin may directly
affect wrinkles. In conclusion, attempt on collagen induction itself is
reasonable and effective strategy in order to keep young appearance, although
oral collagen supplementation may not directly reach to the skin.
PMID- 29332894
TI - Bullous dermatosis on legs of elderly: A new clinical entity?
AB - A lot of diseases occur on the skin of elderly persons. We report four elderly
cases of bullous dermatosis that did not meet various differential diagnoses.
Japanese, heart failure, atrophic skin and leg edema probably due to aging, as
well as flaccid or tense bullae localized in legs were the common factors to our
patients. Such conditions may be increased in coming aging society. Accordingly,
it is worth regarding such symptom as the new clinical entity, which may comfort
patients with similar condition and attract further attention.
PMID- 29332895
TI - Breakthrough mucormycosis after voriconazole use in a case of invasive fungal
rhinosinusitis due to Curvularia lunata.
AB - Invasive fungal rhinosinusitis (FRS) is a potentially fatal illness requiring
early diagnosis and aggressive treatment with surgery and antifungals. We report
a case of chronic FRS in a recently diagnosed diabetic individual due to
Curvularia lunata. Imaging revealed extension into the right orbit and right
basifrontal lobe. This was further complicated by development of nosocomial
mucormycosis which was attributed to voriconazole therapy. The patient responded
well to debridement and amphotericin B based therapy. To our knowledge, there are
no reported cases of invasive FRS due to Curvularia lunata. Also, breakthrough
mucormycosis on voriconazole therapy is rarely seen in non-malignancy, non
transplant settings. The possibility of rare fungal infections (community and
nosocomial) should be entertained in developing settings where fungal spores are
ubiquitous.
PMID- 29332896
TI - Iron, Hematological Parameters and Blood Plasma Lipid Profile in Vitamin D
Supplemented and Non-Supplemented Young Soccer Players Subjected to High
Intensity Interval Training.
AB - Vitamin D deficiency has been associated with increased risk for cardiovascular
disease and anemia. Vitamin D-related changes in lipid profile have been studied
extensively but the relationship between vitamin D and lipid metabolism is not
completely understood. As both vitamin D and intermittent training may
potentially affect iron and lipid metabolism, the aim of the study was to
evaluate whether a daily supplementation of vitamin D can modulate the response
of hematological and lipid parameters to high-intensity interval training (HIIT)
in soccer players. Thirty-six young elite junior soccer players were included in
the placebo-controlled, double-blind study. Participants were non-randomly
allocated into either a supplemented group (SG, n=20, HIIT and 5,000 IU of
vitamin D daily) or placebo group (PG, n=16, HIIT and sunflower oil).
Hematological parameters were ascertained before and after the 8-wk training. The
change score (post- and pre-training difference) was calculated for each
individual and the mean change score (MCS) was compared between SG and PG using
the t test and analysis of covariance. There were no differences between SG and
PG at baseline. The red and white cell count, hemoglobin, hematocrit, MCHC,
ferritin, and HDL-cholesterol changed significantly over the 8-wk HIIT. However,
no significant differences in MCS were observed between SG and PG for any
variable. A daily vitamin D supplement did not have any impact on alteration in
hematological or lipid parameters in young soccer players in the course of high
intensity interval training.
PMID- 29332897
TI - Effect of Lithium on the Mechanism of Glucose Transport in Skeletal Muscles.
AB - While lithium is known to stimulate glucose transport into skeletal muscle, the
mechanisms of the increased glucose transport by lithium in skeletal muscle are
not well defined yet. We excised epitrochlearis muscles from male Wistar rats and
measured the transport rates of a glucose analog into lithium-, insulin-, and
muscular contraction-stimulated skeletal muscle tissue and we also analyzed the
levels of cell surface glucose transport 4 using a photolabeling and multicolor
immunofluorescence method. In addition, we generated a cell line that stably
expresses myc-tagged GLUT4 to measure the rates of GLUT4 internalization and
externalization. Lithium significantly increased 2-DG glucose transport rate in
skeletal muscles; however, it was significantly lower than the stimulation
induced by the maximum concentration of insulin or tetanic contraction. But co
treatment of lithium with insulin or tetanic contraction increased glucose
transport rate by ~200% more than lithium alone. When skeletal muscle tissues
were treated with lithium, insulin, and muscular contraction, the levels of cell
surface GLUT4 protein contents were increased similarly by ~6-fold compared with
the basal levels. When insulin or lithium stimuli were maintained, the rate of
GLUT4myc internalization was significantly lower, and lithium was found to
suppress the internalization of GLUT4myc more strongly. The lithium-induced
increase in glucose uptake of skeletal muscles appears to increase in cell
surface GLUT4 levels caused by decreased internalization of GLUT4. It is
concluded that co-treatment of lithium with insulin and muscular contraction had
a synergistic effect on glucose transport rate in skeletal muscle.
PMID- 29332898
TI - Effect of Dietary Protein Levels on Protein Nutritional Status in Growing Female
Rats Kept under Constant Darkness.
AB - The purpose of this study was to clarify the effects of dietary protein levels on
protein nutritional status in rats kept under constant darkness. Thirty-six 4-wk
old female rats (F344 strain) were divided into six groups. Each group was given
a diet with one of three different protein levels and kept under normal light and
dark cycles (7:00-19:00 light period/19:00-7:00 dark period, N group) or under
constant darkness (D group) for 4 wk. The protein levels of the diets were 10%,
20%, and 30% casein. The six groups are referred to as the N10%, N20%, N30%,
D10%, D20%, and D30% groups. Body weight gain was low in the D groups, and that
in the D30% group was much lower than that in the N30% group. The D30% group
retained less nitrogen than the N30% group. As for the amount of urinary nitrogen
excreted every 4 h, the values for the D-groups were higher than those for the N
groups in the 11:00-15:00 periods, and that for the D30% group was higher than
that for the N30% group in the 15:00-19:00 periods, which means that protein
catabolism was higher in the D30% group. It was shown that when rats kept under
constant darkness were fed a high-protein diet for 4 wk, their nitrogen retention
decreased and their protein nutritional state dropped.
PMID- 29332899
TI - Relationship between Dietary Protein or Essential Amino Acid Intake and Training
Induced Muscle Hypertrophy among Older Individuals.
AB - Dietary protein intake is critical for maintaining an optimal muscle mass,
especially among older individuals. Although protein supplementation during
resistance training (RT) has been shown to further augment training-induced
muscle mass in older individuals, the impact of daily variations in protein
intake on training-induced muscle mass has not been explored thus far. Therefore,
this study aimed to investigate the relationship between the dietary protein and
amino acid intake and RT-induced muscle hypertrophy among older individuals. Ten
healthy older men (n=10; mean age=69+/-2 y; body weight (BW)=61.5+/-2.2 kg;
height=1.65+/-0.02 m) participated in progressive RT performed 3 times/wk for 12
wk. Body composition (using DXA) and nutritional assessments (using a 3-d dietary
record) were performed before and after the training period. Leg lean mass (LLM)
increased significantly (15.0+/-0.8 vs. 15.4+/-0.8 kg, p<0.05) after RT, with no
change in dietary nutrient intake. The average dietary protein intake was 1.62+/
0.11 g/kg BW/d, while essential amino acids was 600+/-51 mg/kg BW/d. Although the
correlation between the increase in LLM and dietary protein intake was not
significant, a significant correlation was found between the increase in LLM and
dietary essential amino acid (EAA) intake. Furthermore, there were significant
correlations between the increase in LLM and protein as well as EAA (especially
leucine) intake at breakfast among subjects with suboptimal protein intake
(p<0.05). Our study findings indicate that dietary protein as well as EAA intake
may be significant contributing factors in muscle hypertrophic response during RT
among healthy older men.
PMID- 29332900
TI - Changes in Thyroid Hormone Are Not Involved in Regulating Brain Protein Synthesis
in Adults Rats Fed Ornithine.
AB - Brain protein synthesis and the plasma concentration of growth hormone (GH) are
sensitive to dietary ornithine. However, dietary ornithine does not increase
brain protein synthesis in hypophysectomized rats. Because hypophysectomy may
decrease the secretion of thyroid stimulated hormone (TSH), we assessed whether
the regulation of brain protein synthesis was mediated by changes in the plasma
concentrations of thyroid hormone and ghrelin in the 6-propyl-2-thiouracil (PTU,
thyroid inhibitor)-treated or control adult rats fed ornithine. The four
experimental groups consisted of PTU-treated and control (24-wk-old) male rats
given 0% or 0.7% ornithine-HCl added to a 20% casein diet. The plasma
concentrations of GH and ghrelin, and the fractional rates of protein synthesis
and RNA activity [g protein synthesized/(g RNA*d)] in the brains were
significantly increased after treatment with the 20% casein + 0.7% ornithine
compared with the 20% casein diet alone in both the PTU-treated and control
groups. Ornithine supplementation to the basal diet did not affect the plasma
concentration of T3. The RNA concentration (mg RNA/g protein) was not related to
the fractional rate of protein synthesis in the brain regions. The results
suggest that dietary ornithine likely increases the rate of brain protein
synthesis in control and PTU-treated rats, and that the ornithine-induced
increase in the GH concentration may stimulate mainly brain protein synthesis via
ghrelin. RNA activity is at least partly related to the fractional rate of brain
protein synthesis.
PMID- 29332901
TI - The Relationship between Habitual Dietary Intake and Gut Microbiota in Young
Japanese Women.
AB - Recent studies have shown that dietary content affects the health of the host by
changing the gut microbiota. However, little is known about the association of
microbiota composition with habitual diet in Japanese people. Here, we aimed to
clarify the relationship between the fecal microbiota and habitual dietary intake
of micronutrients, macronutrients and food groups in healthy young Japanese
women. Analysis of fecal microbiota was performed by the terminal restriction
fragment length polymorphism (T-RFLP) method, and a dietary survey was conducted
over three consecutive days using a weighed food record method. T-RFLP pattern
analysis divided the subjects into two clusters, where cluster A group had a high
relative abundance of Bacteroides and Clostridium cluster IV, and cluster B group
had a high relative abundance of Bifidobacterium and Lactobacillales. Cluster A
group also had lower intakes of iron and vitamin K and higher intakes of
mushrooms and snacks than cluster B group. Analysis of Spearman rank correlations
found several significant relationships between fecal microbiota and intake of
nutrients and food groups. Bifidobacterium was correlated with iron intake, and
Clostridium cluster XI was negatively correlated with intakes of cholesterol and
eggs. These results suggest that dietary habits may strongly affect
Bifidobacterium, Bacteroides and Clostridium abundance in the gut microbiota of
young Japanese women. This is the first study to show relationships between fecal
microbiota and habitual dietary intake in Japanese people. Accumulation of
results from similar studies will help to elucidate the relationships between
dietary intake and diseases in Japanese people.
PMID- 29332902
TI - Effects of Enzymatically Synthesized Glycogen and Exercise on Abdominal Fat
Accumulation in High-Fat Diet-Fed Mice.
AB - The combination of diet and exercise is the first choice for the treatment of
obesity and metabolic syndrome. We previously reported that enzymatically
synthesized glycogen (ESG) suppresses abdominal fat accumulation in obese rats.
However, the effect of the combination of ESG and exercise on abdominal fat
accumulation has not yet been investigated. Our goal in this study was therefore
to evaluate the effects of dietary ESG and its combination with exercise on
abdominal fat accumulation in high-fat diet (HFD)-fed mice. Male ICR mice were
assigned to four groups: HFD, HFD containing 20% ESG, HFD with exercise, HFD
containing 20% ESG with exercise. Treadmill exercise was performed for 3 wk (25
m/min, 30 min/d, 3 d/wk) after 5-d adaption to running at that speed. Both ESG
and exercise significantly reduced the weights of abdominal adipose tissues. In
addition, the combination of ESG and exercise significantly suppressed abdominal
fat accumulation, suggesting that ESG and exercise showed an additive effect.
Exercise significantly increased the mRNA levels of lipid metabolism-related
genes such as lipoprotein lipase, peroxisome proliferator-activated receptor
delta; factor-delta (PPARdelta), carnitin palmitoyltransferase b, adipose
triglyceride lipase (ATGL), and uncoupling protein-3 in the gastrocnemius muscle.
On the other hand, dietary ESG significantly decreased the mRNA levels of
PPARdelta and ATGL in the gastrocnemius muscle. These results suggest that the
combined treatment of ESG and exercise effectively suppresses abdominal fat
accumulation in HFD-fed mice by different mechanisms.
PMID- 29332903
TI - Galactose Is the Limiting Factor for the Browning or Discoloration of Cheese
during Storage.
AB - The browning or discoloration of cheese is often observed during long-time
ripening or aging. In the present study, we identified galactose as a limiting
factor for the browning, and clarified the involvement of the Maillard reaction
for the discoloration. A precursor of browning of Cheddar cheese was isolated by
procedures of solvent extraction and chromatography. D-Galactose and D-lactose
were identified as a precursor of browning of Cheddar cheese A and B,
respectively. Cheddar cheese (A, B, and C), sugar-added cheese, and nine kinds of
retail cheese were stored at 4 to 70oC for 0 to 10 d, before the L*-, a*-, and b*
values and sugar contents of each sample were measured. Cheese to which galactose
was added turned brown more intensively during storage than the non-added control
and the other sugar-added cheese. The more galactose was added, the more
intensive the browning of the cheese appeared. The decrease in galactose
correlated with the DeltaL*-, Deltaa*-, Deltab*-, and DeltaE-values indicating
the browning or discoloration of cheese samples. The decrease in sugars of nine
kinds of retail cheese during storage also correlated with the DeltaL*-, Deltaa*
, and DeltaE-values of these cheese samples. These results clearly indicate that
sugars, especially galactose, in cheese are an important factor for the browning
of cheese during storage. In general, a high amount of amino acids, peptides, and
proteins exists in ripe or mature cheese. Therefore, sugars, especially
galactose, were considered to be the limiting factor for the Maillard reaction
causing the browning of ripe or mature cheese during storage.
PMID- 29332904
TI - Detection of Fucoidan in Urine after Oral Intake of Traditional Japanese Seaweed,
Okinawa mozuku (Cladosiphon okamuranus Tokida).
AB - Seaweed has been considered an indigestible food. Fucoidan, which is found
abundantly in seaweed, especially in Cladosiphon okamuranus (Okinawa mozuku), has
a high molecular weight and has been long believed to be hardly absorbed in the
human digestive system due to a lack of certain digestive enzymes. We previously
reported that fucoidan can be detected in serum and urine after oral intake of
purified fucoidan in humans and rats. However, it is unclear whether the fucoidan
in mozuku can be absorbed after digestion of mozuku. Therefore, we attempted to
detect fucoidan in urine before and after mozuku intake. We determined the
fucoidan concentration in urine after oral intake of Okinawa mozuku and urinary
fucoidan was detected in several volunteers. In conclusion, these results suggest
that fucoidan in mozuku can be absorbed after ingestion of mozuku.
PMID- 29332905
TI - Egg White Hydrolysate Improves Glucose Tolerance in Type-2 Diabetic NSY Mice.
AB - We have previously reported that chicken egg white (EW) and low-allergenic EW
hydrolysate (EWH) suppressed ectopic fat accumulation and improved serum glucose
and insulin levels. In this study, the dietary effects of EW and EWH on glucose
tolerance were investigated in different ways to clarify the effect of EW and EWH
on intestinal glucose absorption. Type 2 diabetic Nagoya-Shibata-Yasuda mice were
divided into four groups: a low-fat and low-sucrose casein-based diet group (NL);
high-fat and high-sucrose (HFS) casein-based diet group (NH); HFS EW-based diet
group (NE); and HFS EWH-based diet group (NEH). Mice were fed their respective
diets for 8 wk. At the end of the 6th and 7th week, an oral glucose tolerance
test (OGTT) and insulin tolerance test (ITT) were respectively conducted in
experiment A. At the end of the 7th week, an intraperitoneal glucose tolerance
test (ipGTT) was conducted in experiment B. In experiment A, the plasma glucose
level was suppressed in the NE group during both OGTT and ITT, and suppressed in
the NEH group during OGTT, but not during ITT. In experiment B, the plasma
glucose level was similarly suppressed in the NEH group during ipGTT, but the
suppressive effect was weakened compared to OGTT. Plasma insulin level was lower
in the NE and NEH groups in both experiments. Fecal triacylglycerol excretion was
increased in the NE and NEH groups in experiment A and liver triacylglycerol
content was suppressed in the NE group in experiment B. These findings suggested
that in addition to improving fat metabolism, EWH improves glucose tolerance via
mechanisms related and unrelated to small intestinal function.
PMID- 29332906
TI - A Nuclear Factor Involved in Transcriptional Regulation of the AREBP Gene.
AB - The AICAR responsive element binding protein (AREBP) suppresses transcription of
the gluconeogenic enzyme genes in response to AICAR treatment. Moreover,
overexpression of AREBP also suppresses gluconeogenic gene expressions in
animals, indicating that AREBP plays an important role in gluconeogenesis.
Through a combination of systematic analyses of the AREBP gene promoter and
assays for DNA-protein interaction, we identified a nuclear factor involved in
tissue-specific expression of AREBP. By targeting this nuclear factor,
pharmacological or nutraceutical induction of AREBP gene expression is expected
to reduce blood glucose levels in patient with insulin resistance.
PMID- 29332907
TI - Patients' Characteristics and Clinical Course of Hypertrophic Cardiomyopathy in a
Regional Japanese Cohort - Results From Kochi RYOMA Study.
AB - BACKGROUND: There have been few studies on the clinical course of hypertrophic
cardiomyopathy (HCM) in a community-based patient cohort in Japan.Methods and
Results:In 2004, we established a cardiomyopathy registration network in Kochi
Prefecture (the Kochi RYOMA study) that consisted of 9 hospitals, and finally,
293 patients with HCM were followed. The ages at registration and at diagnosis
were 63+/-14 and 56+/-16 years, respectively, and 197 patients (67%) were male.
HCM-related deaths occurred in 23 patients during a mean follow-up period of
6.1+/-3.2 years. The HCM-related 5-year survival rate was 94%. In addition, a
total of 77 cardiovascular events that were clinically severe occurred in 70
patients, and the HCM-related 5-year event-free rate was 80%. Multivariate Cox
proportional hazards model analysis showed that the presence of NYHA class III at
registration was a significant predictor of HCM-related deaths and that the
presence of atrial fibrillation, lower fractional shortening and presence of left
ventricular outflow tract obstruction in addition to NYHA class III were
significant predictors of cardiovascular events. CONCLUSIONS: In our unselected
registry in an aged Japanese community, HCM mortality was favorable, but one
fifth of the patients commonly suffered from HCM-related adverse cardiovascular
events during the 5-year follow-up period. Careful management of HCM patients is
needed, particularly for those with the above-mentioned clinical determinants.
PMID- 29332908
TI - Optical Coherence Tomography Guidance in Management of Acute Coronary Syndrome
Caused by Plaque Erosion.
AB - For several decades, most physicians have believed that acute coronary syndrome
(ACS) is caused by coronary thrombosis resulting from rupture of vulnerable
plaque characterized by a thin fibrous cap overlying a large necrotic core and
massive inflammatory cell infiltration. However, nearly one-third of ACS cases
are caused by plaque erosion characterized by intact fibrous cap, less or absent
necrotic core, less inflammation, and large lumen. Because of the limitations of
current imaging modalities, including angiography and intravascular ultrasound,
the importance of plaque erosion as a cause of acute coronary events is less well
known. Optical coherence tomography (OCT) as an emerging modality with extremely
high resolution is the only intravascular imaging modality available for
identification of plaque erosion in vivo, which provides new insight into the
mechanism of ACS. More importantly, the introduction of OCT to clinical practice
enables us to differentiate the patients with ACS caused by plaque erosion from
those caused by plaque rupture, thereby providing precise and personalized
therapy based on the different underlying mechanisms. We systematically review
the morphological characteristics of plaque erosion identified by OCT and its
implications for the management of ACS.
PMID- 29332909
TI - Type 2 Myocardial Infarction - An Evolving Entity.
AB - Type 2 myocardial infarction (T2MI) refers to myocardial necrosis caused by an
imbalance in myocardial oxygen supply and demand and in the absence of acute
coronary thrombosis. Despite growing recognition of this entity, there remains
little understanding of the pathophysiology and uncertainty over the diagnostic
criteria for this subtype of MI. Alarmingly, recent studies suggest that a
diagnosis of T2MI pertains a prognosis similar to, if not worse than, type 1 MI.
With increasing clinical use of high-sensitivity cardiac troponin assays, the
frequency of recognition of T2MI is expected to increase. Yet, there remains a
scarcity of prospective studies examining this cohort of patients, let alone
randomized clinical trials identifying optimum treatment strategies. Further
evaluation of the prevalence, pathophysiology and management of this patient
cohort is warranted by the scientific community.
PMID- 29332910
TI - Successful Infant Pneumonectomy with Unilateral Pulmonary Artery Occlusion Test.
AB - The use of unilateral pulmonary artery occlusion (UPAO) test for the preoperative
evaluation of pneumonectomy was reported in adult patients. On the contrary, in
infants, no strategies have yet been recommended to predict hemodynamics after
pneumonectomy, nor has use of the UPAO test been reported. We describe the first
case of infant with abnormal pulmonary circulation in whom successful
pneumonectomy was performed after preoperative evaluation using UPAO test. Right
pneumonectomy was planned for an 8-month-old girl, because of decreased right
pulmonary function, high risk of pneumothorax, and impaired left lung expansion
due to overexpansion caused by severe left bronchial stenosis and bronchomalacia.
However, she had also prolonged pulmonary hypertension and there was difficulty
in accurate echocardiographic evaluation of its severity due to concomitant left
pulmonary artery stenosis. Furthermore, contrast-enhanced computer tomography
suggested a certain degree of right pulmonary venous flow, discordant with the
result showing scarce right pulmonary flow in perfusion scintigraphy. Predicting
postoperative hemodynamic changes was therefore considered difficult. To evaluate
these concerns, we performed cardiac catheterization and UPAO test to simulate
postoperative hemodynamics. Pulmonary arteriography showed decreased but
significant right pulmonary arterial and venous flows. Measurements including
pulmonary artery pressure and cardiac index showed no marked changes after
occlusion. Based on UPAO test results, the operation was successfully performed
and hemodynamics remained stable postoperatively. The UPAO test may be useful for
infants with cardiopulmonary impairment to evaluate the tolerability of
pneumonectomy.
PMID- 29332911
TI - Impact of Continuous Administration of Tolvaptan on Preventing Medium-Term
Worsening Renal Function and Long-Term Adverse Events in Heart Failure Patients
with Chronic Kidney Disease.
AB - Tolvaptan (TLV) has an inhibiting effect for worsening renal function (WRF) in
acute decompensated heart failure (HF) patients. However, there are limited data
regarding the effect of continuous TLV administration on medium-term WRF.This was
a retrospective observational study in hospitalized HF patients with chronic
kidney disease (CKD). TLV was administered to those patients with fluid retention
despite standard HF therapy. We compared 34 patients treated with TLV (TLV group)
to 33 patients treated with conventional HF therapy with high-dose loop diuretics
(furosemide >= 40 mg) (Loop group). Clinical outcomes, including the incidence of
medium-term WRF, defined as increase of serum creatinine > 0.3 mg/dL, at 6 months
after discharge and adverse events rate, were evaluated.Baseline patient
characteristics were not different between the TLV and Loop group. The TLV group
consisted of less frequent use of loop diuretics and carperitide compared with
the Loop group. The incidence of medium-term WRF was significantly lower in the
TLV group than in the Loop group (3.2% versus 31.0%, P = 0.002). Multivariate
logistic analysis showed that the TLV non-user was an independent predictor of
medium-term WRF. Kaplan-Meier analysis revealed that the long-term event-free
survival was significantly higher in the TLV group (log-rank P = 0.01).Continuous
administration of TLV may reduce the risk of medium-term WRF, resulting
possibility in improvement of long-term adverse outcomes in HF patients with CKD.
PMID- 29332913
TI - Early Extubation in the Operating Room after Congenital Open-Heart Surgery.
AB - Early extubation in the operating room after congenital open-heart surgery is
feasible, but extubation in the intensive care unit after the operation remains
common practice at many institutions. The purpose of this study was to evaluate
retrospectively the adequacy of our early-extubation strategy and exclusion
criteria through analysis based on the Risk Adjustment in Congenital Heart
Surgery method (RACHS-1).This retrospective analysis included 359 cases requiring
cardiopulmonary bypass (male, 195; female, 164; weight > 3.0 kg; aged 1 month to
18 years). Neonates and preoperatively intubated patients were excluded. Other
exclusion criteria included severe preoperative pulmonary hypertension, high-dose
catecholamine requirement after cardiopulmonary bypass, delayed sternal closure,
laryngomalacia, serious bleeding, and delayed awakening. The early-extubation
rates were compared between age groups and RACHS-1 classes.Overall, 83% of cases
(298/359) were extubated in the operating room, classified by RACHS-1 categories
as follows: 1, 59/59 (100%); 2, 164/200 (84%); 3, 61/78 (78%); and 4-6, 10/22
(45%). The early extubation rate in categories 1-3 (86%, 288/337) was
significantly higher than for categories 4-6 (45.5%, 10/22) (P < 0.001). Because
they met one of the exclusion criteria, 61 patients (17%) were not extubated in
the operating room. Eight patients (2.7%) required re-intubation after early
extubation in the operating room, and longer operation time was significantly
associated with re-intubation (P < 0.001).Extubation in the operating room after
congenital open-heart surgery was feasible based on our criteria, especially for
patients in the low RACHS-1 categories, and involves a very low rate of re
intubation.
PMID- 29332912
TI - Impairment of Iodine-123-Metaiodobenzylguanidine (123I-MIBG) Uptake in Patients
with Pulmonary Artery Hypertension.
AB - According to recent studies, lung uptake of iodine-123-metaiodobenzylguanidine
(123I-MIBG) is impaired in many lung diseases and low lung uptake of 123I-MIBG
suggests endothelial dysfunction of the pulmonary artery. 123I-MIBG scintigraphy
in patients with pulmonary hypertension (PH) has not yet been clinically
evaluated. We hypothesized that the lung uptake of 123I-MIBG is reduced in
patients with PH and differs among PH subtypes. The purpose of the present study
was to analyze the lung uptake of 123I-MIBG in patients with PH and compare it
with the data obtained by echocardiography or right heart catheterization. 123I
MIBG scintigraphy was performed in 286 consecutive patients from 2003 to 2014. We
enrolled 21 patients with PH and 8 control patients. The 21 patients with PH were
categorized into those with pulmonary artery hypertension (PAH, n = 12) and those
with chronic thromboembolic pulmonary hypertension (CTEPH, n = 9). The mean
pulmonary artery pressure was not significantly different between patients with
CTEPH and PAH (37.7 +/- 6.8 versus 32.3 +/- 5.3 mmHg respectively; P = 0.054).
There were no significant differences in any other hemodynamic parameters between
the two groups. The lung uptake of 123I-MIBG in PAH patients (early image: 1.54
+/- 0.18, delayed image: 1.41 +/- 0.16) was significantly lower than that of
CTEPH patients (early image: 2.17 +/- 0.25, P < 0.0001; delayed image: 1.99 +/-
0.20, P = 0.0001, adjusted for age and World Health Organization classification)
and controls (early image: 2.32 +/- 0.27, P = 0.0007; delayed image: 1.92 +/-
0.19, P = 0.0007). In conclusion, we found for the first time that the lung
uptake of 123I-MIBG in patients with PAH is lower than that in patients with
CTEPH and controls.
PMID- 29332914
TI - Long-Term Clinical Outcomes after Treatment with Excimer Laser Coronary
Atherectomy for In-Stent Restenosis of Drug-Eluting Stent.
AB - Excimer laser coronary atherectomy (ELCA) has been used for the treatment of
complex percutaneous coronary intervention (PCI) such as in-stent restenosis
(ISR). However, little information was provided about the clinical outcomes after
treatment with ELCA for ISR of drug-eluting stents (DES). This study aimed to
investigate the long-term clinical outcomes after PCI with ELCA for ISR of DES.A
total of 81 consecutive patients with 87 lesions who underwent PCI for ISR of DES
were included. Patients were classified into a PCI with ELCA group (23 patients
with 24 lesions) and a PCI without ELCA group (58 patients with 63 lesions). The
major adverse cardiac events (MACE) were evaluated. The mean duration of clinical
follow-up was 29.8 +/- 11.6 months. The incidences of diffuse restenosis and
AHA/ACC type B2 or C lesion in the PCI with ELCA group were higher than in the
PCI without ELCA group. Quantitative coronary angiography showed the acute
luminal gain in the PCI with ELCA group was greater than in the PCI without ELCA
group (1.64 +/- 0.48 mm versus 1.26 +/- 0.42 mm, P < 0.001). There were no
significant differences in all-cause death, myocardial infarction, or target
lesion revascularization between the 2 groups. Multivariate analysis due to a Cox
proportional-hazards model showed that multivessel disease was an independent
predictor of MACE (hazard ratio 3.05, 95% confidence interval 1.22 to 7.61, P =
0.02). ELCA was effective as an atherectomy device for lumen enlargement and
optimal lesion preparation. Even though ELCA was used for ISR of DES in
significantly more complex lesions, the long-term clinical outcomes were
favorable and similar.
PMID- 29332915
TI - Calcified Amorphous Tumor-Induced Acute Cerebral Infarction.
AB - We report the case of a 38-year-old woman who was admitted for acute cerebral
infarction linked to a cardiac calcified amorphous tumor (CAT) and related mitral
annular calcification (MAC). The cardiac mass was removed, and mitral valve
replacement surgery was performed. Pathological examination revealed an amorphous
accumulation of degenerating material within both lesions, indicating that build
up of calcium along the mitral annulus and subsequent rupture of the fibrotic
tissue may be involved in the initiation and progression of CAT.
PMID- 29332916
TI - MiR-135a Promotes Inflammatory Responses of Vascular Smooth Muscle Cells From
db/db Mice via Downregulation of FOXO1.
AB - It has been shown that microRNAs (miRNAs) greatly affect the functions of
vascular smooth muscle cells (VSMC), but the effects of mRNAs under diabetic
conditions remain unclear.Using a model of diabetic db/db mice, we studied the
functions of microRNA-135a (miR-135a) during VSMC dysfunction.Compared to control
WT mice, miR-135a expression in VSMC was significantly increased while the level
of forkhead box O1 (FOXO1) protein decreased significantly. After transfecting
miR-135a mimics into VSMC, the expression of FOXO1 was decreased, while
cyclooxygenase-2 (COX-2) and monocyte chemoattractant protein-1 (MCP-1)
expression levels were increased, thus promoting the interaction between
monocytes and WT VSMC. On the other hand, transfection of an miR-135a inhibitor
reversed the activated interaction between monocytes and db/db VSMC. The pro
inflammatory responses could also be enhanced by using siRNAs to silence the
FOXO1 gene in WT VSMC, suggesting a negative regulatory role of FOXO1. FOXO1
siRNAs and miR-135a mimics could both enhance the transcriptional activity of COX
2 promoter. Using chromatin immunoprecipitation, we found that in db/db VSMC, the
occupancy in promoter regions of inflammatory genes by FOXO1 was reduced.miR-135a
increased the inflammatory responses of VSMC involved in complications of
vascular diseases by downregulating the expression of FOXO1.
PMID- 29332917
TI - Significance of Sarcopenia Evaluation in Acute Decompensated Heart Failure.
AB - In patients with chronic heart failure (HF), the clinical importance of
sarcopenia has been recognized in relation to disease severity, reduced exercise
capacity, and adverse clinical outcome. Nevertheless, its impact on acute
decompensated heart failure (ADHF) is still poorly understood. Dual-energy X-ray
absorptiometry (DXA) is a technique for quantitatively analyzing muscle mass and
the degree of sarcopenia. Fat-free mass index (FFMI) is a noninvasive and easily
applicable marker of muscle mass.This was a prospective observational cohort
study comprising 38 consecutive patients hospitalized for ADHF. Sarcopenia,
derived from DXA, was defined as a skeletal muscle mass index (SMI) two standard
deviations below the mean for healthy young subjects. FFMI (kg/m2) was calculated
as 7.38 + 0.02908 * urinary creatinine (mg/day) divided by the square of height
(m2).Sarcopenia was present in 52.6% of study patients. B-type natriuretic
peptide (BNP) levels were significantly higher in ADHF patients with sarcopenia
than in those without sarcopenia (1666 versus 429 pg/mL, P < 0.0001). Receiver
operator curves were used to compare the predictive accuracy of SMI and FFMI for
higher BNP levels. Areas under the curve for SMI and FFMI were 0.743 and 0.717,
respectively. Multiple logistic regression analysis showed sarcopenia as a
predictor of higher BNP level (OR = 18.4; 95% CI, 1.86-181.27; P =
0.013).Sarcopenia is associated with increased disease severity in ADHF. SMI
based on DXA is potentially superior to FFMI in terms of predicting the degree of
severity, but FFMI is also associated with ADHF severity.
PMID- 29332918
TI - Plasmatic MicroRNA Signatures in Elderly People with Stable and Unstable Angina.
AB - We aimed to investigate the distinctive miRNA profiles in the plasma of elderly
patients with unstable angina (UA) and stable angina (SA), and to find more
effective markers of UA in elderly people. We compared miRNA expression levels in
plasma samples from 10 elderly patients with UA and 10 elderly patients with SA
by using microarray-based miRNA chip, and then performed validation with Real
time PCR. Mir-1202, mir-1207-5p, and mir-1225-5p showed a statistically
significant down-regulation (P < 0.05), while mir-3162-3p showed an up-regulation
(P < 0.05) during validation. Among all single miRNAs, miR-3162-3p showed the
highest discriminatory power in the diagnosis of elderly patients with UA (AUC:
0.79, 95% CI: 0.675-0.905). The discriminatory power of a panel of three miRNAs
(mir-3162-3p/mir-1225-5p/mir-1207-5p) was highest with an AUC of 0.91 (95% CI:
0.84-0.98), followed by mir-3162-3p/mir-1225-5p (AUC: 0.833, 95% CI: 0.732-0.934)
and mir-3162-3p/mir-1207-5p (AUC: 0.817, 95% CI: 0.712-0.922). In conclusion,
multi-miRNA panel could provide higher diagnostic value for the diagnosis of
elderly patients with UA.
PMID- 29332919
TI - High-Intensity Interval Training for Severe Left Ventricular Dysfunction Treated
with Left Ventricular Assist Device.
AB - Aerobic training based on anaerobic threshold (AT) is well-known to improve
cardiac function, exercise capacity, and long-term outcomes of patients with
heart failure. Recent reports suggested that high-intensity interval training
(HIIT) for patients with cardiovascular disease may improve cardiopulmonary
exercise capacity. We present a 61-year-old male patient of severe left
ventricular dysfunction with left ventricular assisted device (LVAD). Following
HIIT for 8 weeks, exercise capacity and muscle strength have improved without
worsening left ventricular function. Our case showed the possibility that HIIT
was feasible and effective even in patients with LVAD.
PMID- 29332920
TI - Aorto-Cutaneous Fistula after Surgical Treatment of Stanford Type A Aortic
Dissection.
AB - An aorto-cutaneous fistula is a rare complication that occurs after aortic
surgery. Due to its rarity, postoperative complications are not normally
highlighted in most standard teaching. We report here a case of aorto-cutaneous
fistula after surgical treatment of a Stanford type A aortic dissection (AD) in a
67-year-old Chinese male. The patient presented with severe right heart
dysfunction and a mass was found in the upper-middle of his chest, which started
bleeding in the next years. On admission, preoperative aortic computed tomography
angiography (CTA) showed a huge hematoma located in the anterior superior
mediastinum and a shunt between the embedding cavity of the aortic root and right
atrium. An emergent procedure was performed. Intraoperatively, we found two leaks
approximately 2 mm from the anastomosis of the greater curvature of the ascending
aortic graft and stented graft after the hematoma was cleared and we confirmed
the shunt had a large amount of blood flow after a right atrium incision. After
the surgery, the patient was diagnosed with a cerebral hemorrhage, and his family
decided to refuse therapy on the third postoperative day (p.o.d.).
PMID- 29332921
TI - Early Diastolic Left Ventricular Relaxation in Normal Neonates is Influenced by
Ventricular Stiffness and Longitudinal Systolic Function.
AB - Tissue Doppler velocity during early diastole (e') is one of the most feasible
and reproducible echocardiographic assessments to reflect active relaxation of
the left ventricle. Although several reports have described the mechanisms of
temporal diastolic dysfunction in the early neonatal period, factors influencing
diastolic function have not been determined. The purpose of this study was to
elucidate factors significantly influencing e' in the early neonatal period.A
total of 179 consecutive normal neonates underwent echocardiographic studies
performed at 0 days and 5-10 days after birth. The statistical relationships
between e' and age, body weight, mean blood pressure, heart rate, shortening
fraction of the left ventricle, peak systolic motion velocity (s'), early
diastolic transmitral flow velocity over annulus velocity, Tei index, and
diastolic wall strain (DWS) were analyzed.Between the 0 days and 5-10-days-after
birth groups, significant differences were shown in mean blood pressure,
shortening fraction of left ventricle, e', and Tei index. Age, body weight, mean
blood pressure, s', and DWS showed significant correlations with e'. In
multivariate regression analysis within these parameters, s' (beta = 0.6119, P <
0.0001) and DWS (beta = 0.1216, P = 0.0321) showed positive correlations with
e'.Longitudinal systolic motion velocity and ventricular wall stiffness of the
left ventricle influence diastolic relaxation in normal neonates. Age, body
weight, and circumferential systolic function are not significant factors.
PMID- 29332922
TI - Role of Gene Polymorphisms/Haplotypes and Plasma Level of TGF-beta1 in
Susceptibility to In-Stent Restenosis Following Coronary Implantation of Bare
Metal Stent in Chinese Han Patients.
AB - Transforming growth factor (TGF)-beta1 has been implicated in the pathogenesis of
restenosis. However, the role of TGF-beta1 polymorphisms in development of in
stent restenosis (ISR) after coronary bare metal stent (BMS) implantation in
Chinese Han population has not been reported to date. The aim of this study was
to explore the association between TGF-beta1 gene polymorphisms (-509C/T and
869T/C) and its plasma level in Chinese Han patients with BMS-ISR.We investigated
419 patients after successful coronary stent placement. All patients were
reexamined by angiography. Genotyping for the two TGF-beta1 gene polymorphisms
was performed using polymerase chain reaction-restriction fragment length
polymorphism analysis. Plasma TGF-beta1 levels were measured by enzyme-linked
immunosorbent assay.Ninety-two patients (21.96%) developed ISR during the follow
up period. The multivariable analysis adjusted for potential confounders and it
revealed that the C allele of TGF-beta1 869T/C polymorphism was linked to an
increased risk of ISR in both additive (Per each C allele) and dominant (TC+CC
versus TT) models with odds ratios (ORs) of 1.88 (95% confidence interval [CI]:
1.21-2.84, P = 0.008) and 2.52 (95% CI: 1.40-4.80, P = 0.005), respectively. In
accord with this, C-dominant CC/CT genotype was linked to higher plasma TGF-beta1
level compared to TT genotype. One haplotype (TC) (-509T, +869C) was associated
with an increased risk for ISR (OR = 1.48, 95% CI: 1.06-2.06, P = 0.010).The C
allele of TGF-beta1 869T/C polymorphism, correlated with high plasma TGF-beta1
level, represented an independent risk factor for BMS-ISR in Chinese Han patients
with coronary artery disease.
PMID- 29332923
TI - Heart Failure as an Aging-Related Phenotype.
AB - The molecular pathophysiology of heart failure, which is one of the leading
causes of mortality, is not yet fully understood. Heart failure can be regarded
as a systemic syndrome of aging-related phenotypes. Wnt/beta-catenin signaling
and the p53 pathway, both of which are key regulators of aging, have been
demonstrated to play a critical role in the pathogenesis of heart failure.
Circulating C1q was identified as a novel activator of Wnt/beta-catenin
signaling, promoting systemic aging-related phenotypes including sarcopenia and
heart failure. On the other hand, p53 induces the apoptosis of cardiomyocytes in
the failing heart. In these molecular mechanisms, the cross-talk between
cardiomyocytes and non-cardiomyocytes (e,g,. endothelial cells, fibroblasts,
smooth muscle cells, macrophages) deserves mentioning. In this review, we
summarize recent advances in the understanding of the molecular pathophysiology
underlying heart failure, focusing on Wnt/beta-catenin signaling and the p53
pathway.
PMID- 29332924
TI - Multiple Recurrent Pseudoaneurysms after Endovascular Repair of Abdominal Aortic
Aneurysm in a Patient with Behcet's Disease.
AB - In Behcet's disease (BD) patients, endovascular repair is a reasonable
alternative treatment for aortic aneurysms to avoid postoperative anastomotic
pseudoaneurysms. However, there are some complications that may occur after
endovascular repair. We herein report the case of a 40-year-old man with active
BD developed recurrent aortic pseudoaneurysms at the proximal and distal margins
of the stent graft and a femoral puncture site pseudoaneurysm 3 months after
endovascular abdominal aortic aneurysm (AAA) repair. The aortic pseudoaneurysms
were treated endovascularly, including the use of the chimney technique for the
proximal pseudoaneurysm close to the renal arteries and the femoral
pseudoaneurysm with surgical excision and reconstruction. Intensive
immunosuppressive therapy was initiated immediately after the operation. The
patient is in good condition without any complications at 8-month follow-up. This
case suggests the utility of the chimney technique and postoperative immediate
intensive immunosuppressive therapy in treating recurrent aortic pseudoaneurysms
in emergency, active BD patients.
PMID- 29332925
TI - Pulmonary Artery Pseudoaneurysm Secondary to Lung Inf lammation.
AB - Pulmonary artery aneurysms (PAA) and pseudoaneurysms (PAP) are caused by
infections, vasculitis, trauma, pulmonary hypertension, congenital heart disease,
and connective tissue disease. Most cases of such aneurysm occur in the trunk or
major branches of the pulmonary artery, while the peripheral type is less common.
The treatment modalities are medical therapy, surgery, and percutaneous catheter
embolization. The mortality rate associated with rupture is approximately 50%. We
encountered a case of a 53-year-old man with a pulmonary artery pseudoaneurysm
secondary to pneumonia and cavity formation during chemotherapy for acute myeloid
leukemia (AML). In diagnosis, contrast-enhanced chest computed tomography (CT)
scan and pulmonary angiography were very useful. He was treated with right middle
and lower lobectomy. After 1-month follow-up, he could restart additional
chemotherapy.
PMID- 29332927
TI - The response of common marmoset immunity against cedar pollen extract.
AB - The in vivo model of pollinosis has been established using rodents, but the model
cannot completely mimic human pollinosis. We used Callithrix jacchus, the common
marmoset (CM), to establish a pollinosis animal model using intranasal weekly
administration of cedar pollen extract with cholera toxin adjuvant. Some of the
treated CMs exhibited the symptoms of snitching, excess nasal mucus and/or
sneezing, but the period was very short, and the symptoms disappeared after
several weeks. The CD4+CD25+ cell ratio in the peripheral blood increased in CMs
quickly after the nasal administration of cedar pollen extract, but the timing
was not parallel with the symptoms. IL-10 mRNA was enhanced in the peripheral
blood mononuclear cells (PBMCs), suggesting CM-induced tolerance for cedar pollen
administration. Similarly, Foxp3 mRNA was also detected in the PBMC. Additive
sensitization of these CMs with Ascaris egg administration did not enhance
chronic inflammation of type 1 allergy to induce the symptoms. These results
suggest that the environmental immune cells develop transient allergic symptoms
and subsequent immune-tolerance in the intranasally sensitized CMs.
PMID- 29332926
TI - Differentiating between Alzheimer Disease Patients and Controls with Phase
difference-enhanced Imaging at 3T: A Feasibility Study.
AB - PURPOSE: To test the feasibility of the phase difference enhanced (PADRE) imaging
for differentiation between Alzheimer disease (AD) patients and control subjects
on 3T MR imaging. MATERIALS AND METHODS: Fifteen patients with AD and 10 age
matched control subjects underwent two-dimensional fast field echo imaging to
obtain PADRE images on a 3T MR scanner. A double Gaussian distribution model was
used to determine the threshold phase value for differentiation between the
physiologic and non-physiologic iron in the cerebral cortices, and PADRE images
were processed with the threshold. Using a 4-point grading system, two readers
independently assessed the signal of the four cerebral cortices on PADRE images:
the cuneus, precuneus, superior frontal gyrus, and superior temporal gyrus. The
difference in the signals in each cortex between the AD patients and age-matched
control subjects was determined by using Mann-Whitney U test. Inter-rater
reliability was determined by Kappa analysis. We also evaluated the correlation
between Mini-Mental State Examination (MMSE) score and the hypointense grade, and
between disease duration and the hypointense grade using the Spearman rank
correlation test. RESULTS: The threshold phase value for differentiation between
the physiologic and non-physiologic iron was -4.6% pi (radian). The mean grades
of the cuneus, precuneus, and superior temporal gyrus were significantly higher
for the AD patients than for the control subjects (P = 0.002). Excellent inter
rater reliability was seen in the precuneus (kappa = 0.93), superior temporal
gyrus (kappa = 0.94), and superior frontal gyrus (kappa = 0.93); good inter-rater
reliability was observed in the cuneus (kappa = 0.75). We found a statistical
correlation between MMSE score and the hypointense grade in superior temporal
gyrus (STG) (P = 0.008), and no correlation between disease duration and the
hypointense grade in any gyrus. CONCLUSION: Our results suggest the feasibility
of PADRE imaging at 3T for differentiation between AD patients and control
subjects.
PMID- 29332928
TI - Optical coherence tomography for precision brain imaging, neurosurgical guidance
and minimally invasive theranostics.
AB - This review focuses on optical coherence tomography (OCT)-based neurosurgical
application for imaging and treatment of brain tumors. OCT has emerged as one of
the most innovative and successful translational biomedical-diagnostic
techniques. It is a useful imaging tool for noninvasive, in vivo, in situ and
real-time imaging in soft biological tissues, such as brain tumor imaging. OCT
can detect the structure of biological tissue in a micrometer scale, and
functional OCT has some clinical researches and applications, such as nerve fiber
tracts and neurovascular imaging. OCT is able to identify tumor margins, and it
gives intraoperative precision identification and resection guidance. OCT-based
theranostics is introduced into preclinical neurosurgical resection, such as the
integration of OCT and laser ablation. We discuss the challenges and
opportunities of OCT-based system in the field of combination of intraoperative
structural and functional imaging, neurosurgical guidance and minimally invasive
theranostics. We point out that OCT and laser ablation-based theranostics can
give more precision and intelligence for intraoperative diagnosis and
therapeutics in clinical applications. The theranostics can precisely locate, or
specifically target cancerous tissues, and then as much as possiblly eliminate
them.
PMID- 29332929
TI - Size-Based Differentiation of Cancer and Normal Cells by a Particle Size Analyzer
Assisted by a Cell-Recognition PC Software.
AB - Detection of anomalous cells such as cancer cells from normal blood cells has the
potential to contribute greatly to cancer diagnosis and therapy. Conventional
methods for the detection of cancer cells are usually tedious and cumbersome.
Herein, we report on the use of a particle size analyzer for the convenient size
based differentiation of cancer cells from normal cells. Measurements made using
a particle size analyzer revealed that size parameters for cancer cells are
significantly greater (e.g., inner diameter and width) than the corresponding
values for normal cells (white blood cells (WBC), lymphocytes and splenocytes),
with no significant difference in shape parameters (e.g., circularity and
convexity). The inner diameter of many cancer cell lines is greater than 10 um,
in contrast to normal cells. For the detection of WBC having similar size to that
of cancer cells, we developed a PC software "Cancer Cell Finder" that
differentiates them from cancer cells based on brightness stationary points on a
cell surface. Furthermore, the aforementioned method was validated for cancer
cell/clusters detection in spiked mouse blood samples (a B16 melanoma mouse
xenograft model) and circulating tumor cell cluster-like particles in the cat and
dog (diagnosed with cancer) blood samples. These results provide insights into
the possible applicability of the use of a particle size analyzer in conjunction
with PC software for the convenient detection of cancer cells in experimental and
clinical samples for theranostics.
PMID- 29332930
TI - Bullosis Diabeticorum: A Rare Presentation with Immunoglobulin G (IgG) Deposition
Related Vasculopathy. Case Report and Focused Review.
AB - BACKGROUND Bullosis diabeticorum (BD) is a condition characterized by recurrent,
spontaneous, and non-inflammatory blistering in patients with poorly controlled
diabetes mellitus. While etiopathogenesis remains unclear, roles of neuropathy,
vasculopathy and UV light are hypothesized. Most literature reports negative
direct and indirect immunofluorescence findings in diabetics with bullous
eruptions. Porphyria cutanea tarda, bullous pemphigoid, epidermolysis bullosa,
and pseudoporphyria are other differential diagnoses of bullous lesions, and they
must be excluded. CASE REPORT We present a 42-year-old African American male with
long standing poorly controlled insulin dependent diabetes mellitus with blisters
on his left hand and feet. The blisters were noticed three weeks prior to
presentation and, thereafter, rapidly increased in size and spontaneously
ruptured. Physical examination revealed a multitude of both roofed and unroofed
bullous painless skin lesions. Hematoxylin and eosin (H&E) staining dramatized
the dermal-epidermal blistering and re-epithelization process. Direct
Immunofluorescence (DIF) was positive for 2 + IgG deposition in the already
thickened basement membrane of the capillaries of the superficial vascular
plexus. After debridement, his wounds greatly improved with over three months of
aggressive wound care. CONCLUSIONS Primary immunologic abnormality likely plays
no role in the onset of BD. To date, only one article has reported nonspecific
capillary-associated immunoglobulin M and C3. This is the first case of BD with
IgG deposition in the superficial capillary basement membrane. Positive findings
on DIF suggest vasculopathy. Dermal microangiopathy, secondary to immunologic
abnormality, is a possible underlying pathogenesis to bullae formation. Punch
biopsy with DIF can be an additional diagnostic modality in the management of
such cases.
PMID- 29332932
TI - Thrombotic microangiopathy: Pregnancy outcomes in aHUS.
PMID- 29332933
TI - Epigenetics: H3K27me3 in glomerular disease.
PMID- 29332931
TI - Proteasome Inhibitor Carbobenzoxy-L-Leucyl-L-Leucyl-L-Leucinal (MG132) Enhances
Therapeutic Effect of Paclitaxel on Breast Cancer by Inhibiting Nuclear Factor
(NF)-kappaB Signaling.
AB - BACKGROUND Carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG132), a peptide aldehyde
proteasome inhibitor, can inhibit tumor progression by inactivating nuclear
factor (NF)-kappaB signaling. Paclitaxel (PTX) is part of a routine regimen for
the treatment of breast cancer. However, activation of the NF-kappaB pathway
after treatment with PTX confers insensitivity to this drug. This study
investigated the potential effect of MG132 as a co-treatment with PTX against
breast cancer, and clarifies the underlying molecular mechanisms. MATERIAL AND
METHODS Breast cancer cells were treated with PTX, MG132, or PTX plus MG132, and
the therapeutic effects were evaluated phenotypically. A mouse model of breast
cancer was used to determine the combined effect of PTX plus MG132 in vivo.
RESULTS Treatment with PTX plus MG132 suppressed aggressive phenotypes of breast
cancer cells more effectively than PTX alone. Consistently, MG132 also enhanced
the suppressive effect of PTX on tumor growth in C57BL/6 mice. Significantly,
activation of the NF-kappaB pathway by PTX was attenuated by MG132. CONCLUSIONS
Based on our findings, we suggest the application of MG132 in clinical practice
in combination with PTX for the treatment of breast cancer.
PMID- 29332934
TI - Sepsis: The podoplanin-CLEC2 axis in sepsis.
PMID- 29332938
TI - Innate lymphoid cells: Lipid surveillance by skin ILCs.
PMID- 29332939
TI - Metagenomics: Setting the bar for mycobiome analysis.
PMID- 29332936
TI - Tissue-specific immunopathology during malaria infection.
AB - Systemic inflammation mediated by Plasmodium parasites is central to malaria
disease and its complications. Plasmodium parasites reside in erythrocytes and
can theoretically reach all host tissues via the circulation. However, actual
interactions between parasitized erythrocytes and host tissues, along with the
consequent damage and pathological changes, are limited locally to specific
tissue sites. Such tissue specificity of the parasite can alter the outcome of
malaria disease, determining whether acute or chronic complications occur. Here,
we give an overview of the recent progress that has been made in understanding
tissue-specific immunopathology during Plasmodium infection. As knowledge on
tissue-specific host-parasite interactions accumulates, better treatment
modalities and targets may emerge for intervention in malaria disease.
PMID- 29332940
TI - Cellular microbiology: Many pathogens, one host receptor.
PMID- 29332941
TI - Bacterial pathogenesis: Clostridium difficile is sweet on trehalose.
PMID- 29332937
TI - Improving immune-vascular crosstalk for cancer immunotherapy.
AB - The vasculature of tumours is highly abnormal and dysfunctional. Consequently,
immune effector cells have an impaired ability to penetrate solid tumours and
often exhibit compromised functions. Normalization of the tumour vasculature can
enhance tissue perfusion and improve immune effector cell infiltration, leading
to immunotherapy potentiation. However, recent studies have demonstrated that the
stimulation of immune cell functions can also help to normalize tumour vessels.
In this Opinion article, we propose that the reciprocal regulation between tumour
vascular normalization and immune reprogramming forms a reinforcing loop that
reconditions the tumour immune microenvironment to induce durable antitumour
immunity. A deeper understanding of these pathways could pave the way for
identifying new biomarkers and developing more effective combination treatment
strategies for patients with cancer.
PMID- 29332942
TI - 1918 influenza virus: 100 years on, are we prepared against the next influenza
pandemic?
PMID- 29332943
TI - Bacterial physiology: It's a wrap for Burkholderia flagella.
PMID- 29332935
TI - Novel treatment strategies for chronic kidney disease: insights from the animal
kingdom.
AB - Many of the >2 million animal species that inhabit Earth have developed survival
mechanisms that aid in the prevention of obesity, kidney disease, starvation,
dehydration and vascular ageing; however, some animals remain susceptible to
these complications. Domestic and captive wild felids, for example, show
susceptibility to chronic kidney disease (CKD), potentially linked to the high
protein intake of these animals. By contrast, naked mole rats are a model of
longevity and are protected from extreme environmental conditions through
mechanisms that provide resistance to oxidative stress. Biomimetic studies
suggest that the transcription factor nuclear factor erythroid 2-related factor 2
(NRF2) offers protection in extreme environmental conditions and promotes
longevity in the animal kingdom. Similarly, during months of fasting,
immobilization and anuria, hibernating bears are protected from muscle wasting,
azotaemia, thrombotic complications, organ damage and osteoporosis - features
that are often associated with CKD. Improved understanding of the susceptibility
and protective mechanisms of these animals and others could provide insights into
novel strategies to prevent and treat several human diseases, such as CKD and
ageing-associated complications. An integrated collaboration between
nephrologists and experts from other fields, such as veterinarians, zoologists,
biologists, anthropologists and ecologists, could introduce a novel approach for
improving human health and help nephrologists to find novel treatment strategies
for CKD.
PMID- 29332944
TI - Fungal pathogenesis: Wheat stem rust effectors revealed.
PMID- 29332946
TI - Optimal Groundwater Extraction under Uncertainty and a Spatial Stock Externality.
AB - We introduce a model that incorporates two important elements to estimating
welfare gains from groundwater management: stochasticity and a spatial stock
externality. We estimate welfare gains resulting from optimal management under
uncertainty as well as a gradual stock externality that produces the dynamics of
a large aquifer being slowly exhausted. This groundwater model imposes an
important aspect of a depletable natural resource without the extreme assumption
of complete exhaustion that is necessary in a traditional single cell (bathtub)
model of groundwater extraction. Using dynamic programming, we incorporate and
compare stochasticity for both an independent and identically distributed as well
as a Markov chain process for annual rainfall. We find that the spatial depletion
of the aquifer is significant to welfare gains for a parameterization of a
section of the Ogallala Aquifer in Kansas, ranging from 2.9% to 3.01%, which is
larger than those found previously over the region. Surprisingly, the inclusion
of stochasticity in rainfall increases welfare gains only slightly.
PMID- 29332947
TI - A tunable coupler for superconducting microwave resonators using a nonlinear
kinetic inductance transmission line.
AB - We present a tunable coupler scheme that allows us to tune the coupling strength
between a feedline and a superconducting resonator in situ over a wide range. In
this scheme, we shunt the feedline with a 50-Omega lumped-element nonlinear
transmission line made from a 20 nm NbTiN film. By injecting a DC current, the
nonlinear kinetic inductance changes and the effective impedance shunting the
resonator periodically varies from a short to an open, which tunes the coupling
strength and coupling quality factor Qc . We have demonstrated Qc tuning over a
factor of 40, between Qc ~ 5.5 * 104 and Qc ~ 2.3 * 106, for a 4.5 GHz resonator
by applying a DC current less than 3.3 mA. Our tunable coupler scheme is easy to
implement and may find broad applications in superconducting detector and quantum
computing/information experiments.
PMID- 29332945
TI - The human skin microbiome.
AB - Functioning as the exterior interface of the human body with the environment,
skin acts as a physical barrier to prevent the invasion of foreign pathogens
while providing a home to the commensal microbiota. The harsh physical landscape
of skin, particularly the desiccated, nutrient-poor, acidic environment, also
contributes to the adversity that pathogens face when colonizing human skin.
Despite this, the skin is colonized by a diverse microbiota. In this Review, we
describe amplicon and shotgun metagenomic DNA sequencing studies that have been
used to assess the taxonomic diversity of microorganisms that are associated with
skin from the kingdom to the strain level. We discuss recent insights into skin
microbial communities, including their composition in health and disease, the
dynamics between species and interactions with the immune system, with a focus on
Propionibacterium acnes, Staphylococcus epidermidis and Staphylococcus aureus.
PMID- 29332948
TI - Comparison of areas in shadow from imaging and altimetry in the north polar
region of Mercury and implications for polar ice deposits.
AB - Earth-based radar observations and results from the MESSENGER mission have
provided strong evidence that permanently shadowed regions near Mercury's poles
host deposits of water ice. MESSENGER's complete orbital image and topographic
datasets enable Mercury's surface to be observed and modeled under an extensive
range of illumination conditions. The shadowed regions of Mercury's north polar
region from 65 degrees N to 90 degrees N were mapped by analyzing Mercury Dual
Imaging System (MDIS) images and by modeling illumination with Mercury Laser
Altimeter (MLA) topographic data. The two independent methods produced strong
agreement in identifying shadowed areas. All large radar-bright deposits, those
hosted within impact craters >=6 km in diameter, collocate with regions of shadow
identified by both methods. However, only ~46% of the persistently shadowed areas
determined from images and ~43% of the permanently shadowed areas derived from
altimetry host radar-bright materials. Some sizable regions of shadow that do not
host radar-bright deposits experience thermal conditions similar to those that
do. The shadowed craters that lack radar-bright materials show a relation with
longitude that is not related to the thermal environment, suggesting that the
Earth-based radar observations of these locations may have been limited by
viewing geometry, but it is also possible that water ice in these locations is
insulated by anomalously thick lag deposits or that these shadowed regions do not
host water ice.
PMID- 29332950
TI - Microwave evaluation of electromigration susceptibility in advanced
interconnects.
AB - Traditional metrology has been unable to adequately address the needs of the
emerging integrated circuits (ICs) at the nano scale; thus, new metrology and
techniques are needed. For example, the reliability challenges in fabrication
need to be well understood and controlled to facilitate mass production of
through-substrate-via (TSV) enabled three-dimensional integrated circuits (3D
ICs). This requires new approaches to the metrology. In this paper, we use the
microwave propagation characteristics to study the reliability issues that
precede the physical damage caused by electromigration in the Cu-filled TSVs. The
pre-failure microwave insertion losses and group delay are dependent on both the
device temperature and the amount of current forced through the devices-under
test. The microwave insertion losses increase with the increase in the test
temperature, while the group delay increases with the increase in the forced
direct current magnitude. The microwave insertion losses are attributed to the
defect mobility at the Cu-TiN interface, and the group delay changes are due to
resistive heating in the interconnects, which perturbs the dielectric properties
of the cladding dielectrics of the copper fill in the TSVs.
https://doi.org/10.1063/1.4992135.
PMID- 29332949
TI - Convergent Synthesis of alpha-Branched Amines by Transition-Metal-Catalyzed C-H
Bond Additions to Imines.
AB - alpha-Branched amines are ubiquitous in drugs and natural products, and
consequently, synthetic methods that provide convergent and efficient entry to
these structures are of considerable value. Transition-metal-catalyzed C-H bond
additions to imines have the potential to be highly practical and atom-economic
approaches for the synthesis of a diverse and complex array of alpha-branched
amine products. These strategies typically employ readily available starting
inputs, display high functional group compatibility, and often avoid the
production of stoichiometric waste byproducts. A number of C-H functionalization
methods have also been developed that incorporate cascade cyclization pathways to
give amine-substituted carbocycles, and in many cases, proceed with the formation
of multiple stereogenic centers. Advances in the area of asymmetric C-H bond
additions to imines have also been achieved through the use of chiral imine N
substituents as well as by enantioselective catalysis.
PMID- 29332951
TI - Soil seal development under simulated rainfall: Structural, physical and
hydrological dynamics.
AB - This study delivers new insights into rainfall-induced seal formation through a
novel approach in the use of X-ray Computed Tomography (CT). Up to now seal and
crust thickness have been directly quantified mainly through visual examination
of sealed/crusted surfaces, and there has been no quantitative method to estimate
this important property. X-ray CT images were quantitatively analysed to derive
formal measures of seal and crust thickness. A factorial experiment was
established in the laboratory using open-topped microcosms packed with soil. The
factors investigated were soil type (three soils: silty clay loam - ZCL, sandy
silt loam - SZL, sandy loam - SL) and rainfall duration (2-14 min). Surface seal
formation was induced by applying artificial rainfall events, characterised by
variable duration, but constant kinetic energy, intensity, and raindrop size
distribution. Soil porosities derived from CT scans were used to quantify the
thickness of the rainfall-induced surface seals and reveal temporal seal micro
morphological variations with increasing rainfall duration. In addition, the
water repellency and infiltration dynamics of the developing seals were
investigated by measuring water drop penetration time (WDPT) and unsaturated
hydraulic conductivity (Kun). The range of seal thicknesses detected varied from
0.6 to 5.4 mm. Soil textural characteristics and OM content played a central role
in the development of rainfall-induced seals, with coarser soil particles and
lower OM content resulting in thicker seals. Two different trends in soil
porosity vs. depth were identified: i) for SL soil porosity was lowest at the
immediate soil surface, it then increased constantly with depth till the median
porosity of undisturbed soil was equalled; ii) for ZCL and SL the highest
reduction in porosity, as compared to the median porosity of undisturbed soil,
was observed in a well-defined zone of maximum porosity reduction c. 0.24-0.48 mm
below the soil surface. This contrasting behaviour was related to different
dynamics and processes of seal formation which depended on the soil properties.
The impact of rainfall-induced surface sealing on the hydrological behaviour of
soil (as represented by WDTP and Kun) was rapid and substantial: an average 60%
reduction in Kun occurred for all soils between 2 and 9 min rainfall, and water
repellent surfaces were identified for SZL and ZCL. This highlights that the
condition of the immediate surface of agricultural soils involving rainfall
induced structural seals has a strong impact in the overall ability of soil to
function as water reservoir.
PMID- 29332952
TI - Disentangling orthogonal matrices.
AB - Motivated by a certain molecular reconstruction methodology in cryo-electron
microscopy, we consider the problem of solving a linear system with two unknown
orthogonal matrices, which is a generalization of the well-known orthogonal
Procrustes problem. We propose an algorithm based on a semi-definite programming
(SDP) relaxation, and give a theoretical guarantee for its performance. Both
theoretically and empirically, the proposed algorithm performs better than the
naive approach of solving the linear system directly without the orthogonal
constraints. We also consider the generalization to linear systems with more than
two unknown orthogonal matrices.
PMID- 29332954
TI - Determination of the Boltzmann constant with cylindrical acoustic gas
thermometry: new and previous results combined.
AB - We report a new determination of the Boltzmann constant kB using a cylindrical
acoustic gas thermometer. We determined the length of the copper cavity from
measurements of its microwave resonance frequencies. This contrasts with our
previous work (Zhang et al 2011 Int. J. Thermophys.32 1297, Lin et al 2013
Metrologia50 417, Feng et al 2015 Metrologia52 S343) that determined the length
of a different cavity using two-color optical interferometry. In this new study,
the half-widths of the acoustic resonances are closer to their theoretical values
than in our previous work. Despite significant changes in resonator design and
the way in which the cylinder length is determined, the value of kB is
substantially unchanged. We combined this result with our four previous results
to calculate a global weighted mean of our kB determinations. The calculation
follows CODATA's method (Mohr and Taylor 2000 Rev. Mod. Phys. 72 351) for
obtaining the weighted mean value of kB that accounts for the correlations among
the measured quantities in this work and in our four previous determinations of
kB. The weighted mean kB is 1.380 6484(28) * 10-23 J K-1 with the relative
standard uncertainty of 2.0 * 10-6. The corresponding value of the universal gas
constant is 8.314 459(17) J K-1 mol-1 with the relative standard uncertainty of
2.0 * 10-6.
PMID- 29332953
TI - Determination of the molar mass of argon from high-precision acoustic
comparisons.
AB - This article describes the accurate determination of the molar mass M of a sample
of argon gas used for the determination of the Boltzmann constant. The method of
one of the authors (Moldover et al 1988 J. Res. Natl. Bur. Stand.93 85-144) uses
the ratio of the square speed of sound in the gas under analysis and in a
reference sample of known molar mass. A sample of argon that was isotopically
enriched in 40Ar was used as the reference, whose unreactive impurities had been
independently measured. The results for three gas samples are in good agreement
with determinations by gravimetric mass spectrometry; ( -
1) = (-0.31 +/- 0.69) * 10-6, where the indicated uncertainty is one standard
deviation that does not account for the uncertainties from the acoustic and mass
spectroscopy references.
PMID- 29332955
TI - Simultaneous segmentation and bias field estimation using local fitted images.
AB - Level set methods often suffer from boundary leakage and inadequate segmentation
when used to segment images with inhomogeneous intensities. To handle this issue,
a novel region-based level set method was developed, in which two different local
fitted images are used to construct a hybrid region intensity fitting energy
functional. This novel method enables simultaneous segmentation of the regions of
interest and estimation of the bias fields from inhomogeneous images. Our
experiments on both synthetic images and a publicly available dataset demonstrate
the feasibility and reliability of the proposed method.
PMID- 29332956
TI - Fitness and Individuality in Complex Life Cycles.
AB - Complex life cycles are common in the eukaryotic world, and they complicate the
question of how to define individuality. Using a bottom-up, gene-centric
approach, I consider the concept of fitness in the context of complex life
cycles. I analyze the fitness effects of an allele (or a trait) on different
biological units within a complex life history and how these effects drive
evolutionary change within populations. Based on these effects, I attempt to
construct a concept of fitness that accurately predicts evolutionary change in
the context of complex life cycles.
PMID- 29332958
TI - Kidney involvement in antiphospholipid syndrome - current diagnostic and
management problems.
PMID- 29332957
TI - In depth examination of impact of secondary reactive species on the apparent
decoupling of poly(ethylene glycol) diacrylate hydrogel average mesh size and
modulus.
AB - Poly(ethylene glycol) diacrylate (PEGDA) hydrogels are widely used in
biotechnology due to their in situ crosslinking capacity and tunable physical
properties. However, as with all single component hydrogels, the modulus of PEGDA
networks cannot be tailored independently of mesh size. This interdependence
places significant limitations on their use for defined, 3D cell-microenvironment
studies and for certain controlled release applications. The incorporation of
secondary reactive species (SRS) into PEGDA hydrogels has previously been shown
to allow the identification of up to 6 PEGDA hydrogel formulations for which
distinct moduli can be obtained at consistent average mesh size (or vice versa).
However, the modulus and mesh size ranges which can be probed by these
formulations are quite restricted. This work presents an in-depth study of SRS
incorporation into PEGDA hydrogels, with the goal of expanding the space for
which "decoupled" examination of modulus and mesh size effects is achievable.
Towards this end, over 100 PEGDA hydrogels containing either N-vinyl pyrrolidone
or star PEG-tetraacrylate as SRS were characterized. To our knowledge, this is
the first study to demonstrate that SRS incorporation allows for the
identification of a number of modulus ranges that can be probed at consistent
average mesh size (or vice versa).
PMID- 29332959
TI - Changes in body composition and bone mineral density in postmenopausal women with
psoriatic arthritis.
AB - Objective: Prolonged inflammation status due to psoriatic arthritis (PsA) may
contribute to the loss of muscle mass, extending from muscle weakness, and
increased risk of falls and fractures. The risk of fractures and their
complications increases with concomitant osteoporosis. Material and methods: The
study included 95 women aged 50-75 years. The presence of sarcopenia was
evaluated in a group of 51 women with PsA, and 44 controls (without inflammatory
joint disease). Measurements of muscle mass and lean body mass were made using
the method of bioimpedance assessing ALM (Appendicular Lean Mass) index and SMI
(Skeletal Muscle Index). The diagnosis of sarcopenia was made in women with low
muscle mass and concomitant reduction of the efficiency of the assessed
functional test Timed Up and Go (TUG). Bone density measurement was done by
densitometry in the femoral neck and lumbar spine. (Ethics statement OIL
625/16/Bioet). Results: Sarcopenia, using ALM index and SMI, was diagnosed in
13.7% and 43.1% of PsA women, and in healthy women in 9% and 20.4%, respectively.
In the group of PsA, sarcopenia was associated with a significant increase in the
occurrence of disorders of bone mineralisation (72.7% vs. 41.3% in patients
without a decrease in muscle mass). There was no correlation between the loss of
muscle mass, bone density, and activity of PsA. Conclusions: The prevalence of
sarcopenia in postmenopausal women suffering from PsA is associated with the
occurrence of osteoporosis.
PMID- 29332960
TI - Nutrition and quality of life referring to physical abilities - a comparative
analysis of a questionnaire study of patients with rheumatoid arthritis and
osteoarthritis.
AB - Objectives: A comparative analysis of opinions on diet and nutrition of patients
suffering from rheumatoid arthritis (RA) and osteoarthritis (OA), and quality of
life limited to physical abilities in both study groups. Material and methods: In
the period from August to December 2012 an anonymous questionnaire survey was
carried out among the patients of the Institute of Rheumatology. The respondents
were asked to define their dietary preferences, dietary supplementation, and the
level of physical limitations by completing the Health Assessment Questionnaire
(HAQ). The study was carried out with the consent of the Bioethics Committee.
Results: A total of 397 questionnaires were obtained. The majority of respondents
were women (77%). 62% of RA patients (165 respondents) had been treated for over
10 years as opposed to OA patients (80 respondents), where the largest group
(33%) were patients during their first year. There is a significant difference in
the disability level of patients in both compared groups. The average HAQ of RA
patients was 1.09 and OA patients - 0.46. A change of dietary habits was declared
by 32% of RA patients and by 17% of OA patients (p = 0.049) mostly without
consulting a specialist - it concerned mainly limiting the consumption of sweets
(30% vs. 21%), a meatless diet: 19% vs. 14%, and a non-dairy diet: 9% vs. 14%.
Conclusions: Regardless of their diagnosis, the respondents believe that the way
of eating affects their health. There are visible differences between diet and
dietary supplementation, depending on the diagnosis of the disease. Differences
were also observed in physical limitations of both patient groups - a higher
level of disability was noted among RA patients. It is necessary to continue the
topic at the level of clinical trials and medical experiments within the scope of
the impact of diet as a supportive element in the treatment of rheumatic
diseases.
PMID- 29332961
TI - The usefulness of histopathological examinations of non-renal biopsies in the
diagnosis of granulomatosis with polyangiitis.
AB - Introduction: Granulomatosis with polyangiitis (GPA) is a rare, ANCA-associated,
systemic disease characterized by necrotizing small and medium vessel vasculitis
of unknown etiology associated with granulomatous inflammation affecting the
renal, pulmonary, upper airways, ocular systems and other tissues. Histological
proof of the granulomatosis with polyangiitis (GPA) can be obtained by biopsy of
clinically involved sites. The main purpose of this study was to examine
histopathological changes in non-renal biopsies from patients with established
diagnosis of GPA and evaluated the histological confirmation at diagnosis of this
disease. Material and methods: A retrospective analysis was performed in patients
with GPA diagnosed and treated in clinics of the University Clinical Center (UCK)
in Gdansk in 1988-2009. Results: In the analyzed group of GPA patients the
histopathological examination of biopsies taken from involved tissues (except
kidney) was performed in 60% of patients. Thirty-six out of 93 biopsies (39%)
were diagnosed as typical of GPA, 10 (10.7%) were suggestive and 51 (54.8%) were
non-specific. Considering all biopsies, the diagnosis was confirmed in 24
patients (57% of patients in whom biopsies were taken). Epitheloid cell
granulomas were present in 33 biopsies (43%), characteristic necrosis in 27
biopsies (35%), small vessel vasculitis in 18 biopsies (23%), while
multinucleated giant cells were identified only in 9 biopsies (12%). Conclusions:
Histopathological examination of the affected tissues remains the gold standard
of the diagnosis of GPA. Its usefulness increases, particularly in ANCA-negative
patients, in the initial phase of the disease, or in patients with atypical
clinical presentation. In many cases, it is necessary to repeat biopsy to
establish the diagnosis. The role of the histopathological examination seems to
be particularly important when ANCA is negative or clinical symptoms are atypical
of GPA.
PMID- 29332962
TI - The importance of physiotherapy in the sexuality of patients with rheumatic
diseases.
AB - The sexuality of patients with rheumatic diseases is a significant
interdisciplinary problem, requiring intensified action not only of
rheumatologists, sexologists, and psychologists but also physiotherapists. The
sexuality problems and motor disability in chronic diseases such as rheumatoid
arthritis or ankylosing spondylitis, as well as other rheumatic diseases, are
generally still taboo subjects, rarely discussed by physicians and
physiotherapists. Lack of mobility, hormonal imbalance, fatigue, and accompanying
decreased quality of life have an impact on sexual dysfunction. Meanwhile sex, as
an integral part of human personality, is an essential element of human life.
PMID- 29332963
TI - Role of human microbiome and selected bacterial infections in the pathogenesis of
rheumatoid arthritis.
AB - Microorganisms inhabiting human body form a complex ecosystem. The mutual
influence of the microbiome and the immune system of the host constitute the
basis for numerous diseases, e.g. pseudomembranous colitis, inflammatory bowel
disease, type 1 diabetes, atopic diseases, obesity, reactive arthritis. New
molecular diagnostic methods and multi-center studies may help in understanding
of the role of microbiota in health and disease. Rheumatoid arthritis has a multi
faceted etiology, and its causes are not entirely understood. There are
indications for the influence of microbiomes of oral cavity, intestines, lungs
and urinary tract on the development of rheumatoid arthritis. Interactions
between microorganisms and human immune system play role in the pathogenesis of
the disease.
PMID- 29332964
TI - Relapse of polymyalgia rheumatica after a fall.
AB - Approximately half of PMR patients have a relapse with a necessity to increase GC
dosages. The role of external factors in inducing PMR relapse have been poorly
investigated. We present a case-series of five PMR patients in remission with low
doses of glucocorticosteroids (GC), who presented with relapse immediately after
a fall. The assessment of PMR relapse was made using PMR-AS by Leeb and Bird, and
a score > 9.35 was consistent with diagnosis of relapse. Gender, age, and
cumulative dose of GC at the time of the fall were compared between the group of
these five patients and a group of 41 PMR patients who had no PMR relapse after a
fall: using the Fischer's exact test a significant difference was pointed out
when the p-value was < 0.05. In our five PMR patients, the sharp worsening of
clinical manifestations was always accompanied by a significant rise of the
inflammatory indices and the increase of GC dosage (almost always 10 mg/day of
prednisone) prompted a fast return (seven days as average) to the previous
clinical and laboratory features. All other potentially responsible factors were
excluded. Several months (6-10 months on average) after the fall, none of these
five patients had a new relapse. No significant differences were found when we
compared age, sex, and the cumulative dose of GC at the time of the fall between
the group of patients with PMR relapse and the group of patients without. The
possibility of PMR relapse being realised immediately after a fall should be kept
in mind in daily practice, especially when typical manifestations reappear
immediately after a fall and other diagnostic hypotheses have been carefully
excluded. The lack of important data (genetic factors, hormonal dosages, serum
levels of IL-6 and/or serum soluble IL-6 receptor) in our case-series represented
important limits for clarifying the nature of our observations and should be
included in any subsequent study design on this argument. If our monocentric data
are confirmed by multicentric data, the assessment of the risk of falls through
specific scales should be an integral part of the visit of all PMR patients.
PMID- 29332965
TI - Two clinical cases of granulomatosis with polyangiitis with isolated otitis media
and mastoiditis.
AB - Granulomatosis with polyangiitis (GPA) is characterised by granulomatous
necrotising inflammatory lesions of the upper and lower respiratory tract, often
associated with pauci-immune glomerulonephritis. The diagnosis of granulomatosis
with polyangiitis is made according to the classification criteria of the ACR
criteria for granulomatosis with polyangiitis. We present two cases of
granulomatosis with polyangiitis limited/localised form. The common feature
between two clinical cases were not sufficient criteria for a definite diagnosis
at the beginning. In both cases the clinical presence was otitis media with acute
mastoiditis, peripheral facial nerve palsy, and severe headache. Early diagnosis
and treatment of patients with granulomatosis with polyangiitis define favourable
prognosis. On the other hand, the treatment of granulomatosis with polyangiitis
(corticosteroids and immunosuppressive therapy) has various side effects, and the
"ex juvantibus" therapy is hazardous.
PMID- 29332966
TI - When nuisance is nice: ignored erythema nodosa heralding the Lofgren's syndrome
in a Nigerian woman.
AB - Lofgren's syndrome (LS) is a variant of sarcoidosis characterised by the triad of
erythema nodosum (EN), radiographic bilateral hilar adenopathy, and
arthralgia/arthritis. Like all cases of sarcoidosis, it is of unknown aetiology
and may constitute a diagnostic difficulty in the ambiguous phenotype. Lofgren's
syndrome is associated with a good prognosis and commonly undergoes spontaneous
remission within four months. However, the co-existence of multiple good and
adverse prognostic factors in a patient may call for guarded expectation.
Sarcoidosis is generally more prevalent among people of African descent, but the
vast majority of the literature on sarcoidosis are from the western hemisphere.
Lofgren's syndrome has been rarely documented in West Africans despite the
availability of some reports of sarcoidosis in the region. We present a case of a
Nigerian woman with LS that started out as isolated EN, which was ignored for
months until the onset of florid pulmonary and systemic symptoms.
PMID- 29332967
TI - Professor Henryka Maldyk (1924-2017).
PMID- 29332968
TI - 50 years of the Polish Physician-Writers Union.
PMID- 29332969
TI - C12H12 interconversions: two non-pyrolytic syntheses of
tricyclo[5.3.2.04,8]dodeca-2,5,9,11-tetraene.
AB - Herein, we describe two independent and non-pyrolytic syntheses of an important
C12H12 hydrocarbon which had been prepared previously by gas phase thermolysis of
compound 6. The first method is based on an unusual dipolar cycloaddition of
dichloroketene onto bullvalene. After reductive dechlorination, a Shapiro-Heath
reaction of the tosylhydrazone gave the title compound. Alternatively, compound
13 is also obtained from its isomer 6 by a Ag+ catalyzed reaction.
PMID- 29332970
TI - MIGRATION AND CONSERVATION: FRAMEWORKS, GAPS, AND SYNERGIES IN SCIENCE, LAW, AND
MANAGEMENT.
AB - Migratory animals provide unique spectacles of cultural, ecological, and economic
importance. However, the process of migration is a source of risk for migratory
species as human actions increasingly destroy and fragment habitat, create
obstacles to migration, and increase mortality along the migration corridor. As a
result, many migratory species are declining in numbers. In the United States,
the Endangered Species Act provides some protection against extinction for such
species, but no protection until numbers are severely reduced, and no guarantee
of recovery to population levels associated with cultural, ecological, or
economic significance. Although groups of species receive some protection from
statutes such as the Migratory Bird Treaty Act and Marine Mammal Protection Act,
there is no coordinated system for conservation of migratory species. In
addition, information needed to protect migratory species is often lacking,
limiting options for land and wildlife managers who seek to support these
species. In this Article, we outline the existing scientific, legal, and
management information and approaches to migratory species. Our objective is to
assess present capacity to protect the species and the phenomenon of migration,
and we argue that al three disciplines are necessary for effective conservation.
We find significant capacity to support conservation in all three disciplines,
but no organization around conservation of migration within any discipline or
among the three disciplines. Areas of synergy exist among the disciplines but not
as a result of any attempt for coordination. As a result, significant gaps in
information and capacity exist that must be addressed if effective conservation
of migratory species is to be undertaken. We suggest that all three disciplines
cooperate to identify the most pressing research needs, so that these can become
targets for relevant funding sources. We identify areas of current risk to
migratory species that represent gaps in current legal protections: protective
legislation that provides no guidelines for desirable population sizes or best
management practices for migratory species, taxonomic groups, particularly those
including long-distance migrants, for which no agency has oversight, and gaps in
policies to address impacts of fragmentation and obstacles such as power lines
and wind turbines that curtail migration or cause mortality. Finally, we suggest
that state-level programs provide either a foundation to augment with, or a model
on which to build, conservation efforts targeting migratory species. Problems
will arise due to lack of funds, difficulties in securing a landscape that will
support abundant migrations, lack of adequate standards and best management
practices, and an insufficient culture of collaboration among the three main
relevant disciplines. However, we view these problems as entirely soluble and see
evidence of support in society at large for conservation of migratory species.
PMID- 29332971
TI - TENSOR DECOMPOSITIONS AND SPARSE LOG-LINEAR MODELS.
AB - Contingency table analysis routinely relies on log-linear models, with latent
structure analysis providing a common alternative. Latent structure models lead
to a reduced rank tensor factorization of the probability mass function for
multivariate categorical data, while log-linear models achieve dimensionality
reduction through sparsity. Little is known about the relationship between these
notions of dimensionality reduction in the two paradigms. We derive several
results relating the support of a log-linear model to nonnegative ranks of the
associated probability tensor. Motivated by these findings, we propose a new
collapsed Tucker class of tensor decompositions, which bridge existing PARAFAC
and Tucker decompositions, providing a more flexible framework for parsimoniously
characterizing multivariate categorical data. Taking a Bayesian approach to
inference, we illustrate empirical advantages of the new decompositions.
PMID- 29332972
TI - Clinical Utility and Measurement of Procalcitonin.
AB - Procalcitonin (PCT), regarded as a biomarker specific for bacterial infections,
is used in a variety of clinical settings including primary care, emergency
department and intensive care. PCT measurement aids in the diagnosis of sepsis
and to guide and monitor antibiotic therapy. This article gives a brief overview
of PCT and its use in guiding antibiotic therapy in various clinical settings, as
well as its limitations. PCT performance in comparison with other biomarkers of
infection in particular CRP is also reviewed. Owing to its greater availability,
CRP has been widely used as a biomarker of infection and sepsis. PCT is often
reported to be more superior to CRP, being more specific for sepsis and bacterial
infection. PCT starts to rise earlier and returns to normal concentration more
rapidly than CRP, allowing for an earlier diagnosis and better monitoring of
disease progression.
PMID- 29332974
TI - The Management of Post Analytical Correction Factors.
AB - Clinical laboratories may systematically apply factors to assay results after
analysis, but before reporting, in order to facilitate comparison of data from
different methods. This may be done to align with other patient results,
reference intervals or clinical decision points. These factors, which we term
Post Analytical Correction Factors (PACF), may be applied to all types of results
derived from the method, i.e. quality control (QC) and external quality assurance
(EQA), as well as the patient results. As the principal use of PACF is comparing
patient results, it is important that the laboratory use commutable materials
(i.e. patient samples) and a formal process to establish, apply and manage PACF.
We report on preliminary guidelines for PACF from a recent workshop.
PMID- 29332975
TI - Enhancing the Clinical Value of Medical Laboratory Testing.
AB - The value of medical laboratory testing is often directed to the cost of testing
however the clinical benefits of these tests are at least as important.
Laboratory testing has an acknowledged widespread role in clinical decision
making, and therefore a role in determining clinical outcome. Consequently, the
value of laboratory testing should be considered in its role in affecting
beneficial actions and outcomes. This includes both the requesting phase of
choosing tests which will influence clinical decision making as well as the
reporting phase in a way that guides clinical decisions and actions. Clinical
decision support systems and software can enhance the value of medical laboratory
testing if they are directed toward facilitating those clinical decisions where
there is either evidence, or agreed consensus, addressing patient outcomes.
PMID- 29332976
TI - Australasian Guideline (2nd Edition): an Annex to the CLSI and UK Guidelines for
the Performance of the Sweat Test for the Diagnosis of Cystic Fibrosis.
PMID- 29332973
TI - Metabologenomics of Phaeochromocytoma and Paraganglioma: An Integrated Approach
for Personalised Biochemical and Genetic Testing.
AB - The tremendous advances over the past two decades in both clinical genetics and
biochemical testing of chromaffin cell tumours have led to new considerations
about how these aspects of laboratory medicine can be integrated to improve
diagnosis and management of affected patients. With germline mutations in 15
genes now identified to be responsible for over a third of all cases of
phaeochromocytomas and paragangliomas, these tumours are recognised to have one
of the richest hereditary backgrounds among all neoplasms. Depending on the
mutation, tumours show distinct differences in metabolic pathways that relate to
or even directly impact clinical presentation. At the same time, there has been
improved understanding about how catecholamines are synthesised, stored, secreted
and metabolised by chromaffin cell tumours. Although the tumours may not always
secrete catecholamines it has become clear that almost all continuously produce
and metabolise catecholamines. This has not only fuelled changes in laboratory
medicine, but has also assisted in recognition of genotype-biochemical phenotype
relationships important for diagnostics and clinical care. In particular,
differences in catecholamine and energy pathway metabolomes can guide genetic
testing, assist with test interpretation and provide predictions about the
nature, behaviour and imaging characteristics of the tumours. Conversely, results
of genetic testing are important for guiding how routine biochemical testing
should be employed and interpreted in surveillance programmes for at-risk
patients. In these ways there are emerging needs for modern laboratory medicine
to seamlessly integrate biochemical and genetic testing into the diagnosis and
management of patients with chromaffin cell tumours.
PMID- 29332978
TI - Playful pigs: Evidence of consistency and change in play depending on litter and
developmental stage.
AB - Play behaviour in pre-weaned piglets has previously been shown to vary
consistently between litters. This study aimed to determine if these pre-weaning
litter differences in play behaviour were also consistent in the post-weaning
period. Seven litters of commercially bred piglets were raised in a free
farrowing system (PigSAFE) and weaned at 28 days post-farrowing (+/-2 days). Post
weaning piglets were maintained in litter groups in the PigSAFE pen. Analyses
have been adjusted for sex both within and between litter as the only
statistically significant covariate to play behaviour. Litter differences were
observed in locomotor play in both the pre- and post-weaning stage (Pre: F(6,76)
= 5.51 P < 0.001; Post: F(6,69) = 4.71, P < 0.001) and run (Pre: F(6,76) = 4.96,
P < 0.001; Post: F(6,69) = 4.58, P < 0.001; the major element of locomotor play).
Twenty eight% of the variance for a single observed animal in pre-weaning
locomotor play and 26% of variance post-weaning could be attributed to the
litter. There was no statistical evidence of differences in social play between
litters at either stage with only 8% of pre-weaning variance, and 1% of post
weaning variance being attributable to the litter level. However non-harmful
fighting (the major element of social play), showed strong evidence of litter
differences in both periods (Pre: F(6,76) = 2.38, P = 0.037; Post: F(6,69) =
2.60, P = 0.025), and was the only aspect of the play behaviour to correlate
between the pre- and post-weaning periods (r = 0.765, df = 5, P = 0.045). On
average play increased post-weaning. Litters showed a 'litter weaning effect' by
differing in their locomotor play behavioural response to weaning, measured as
the change in locomotor play behaviour from pre- to post-weaning (F(6,70) = 5.95,
P < 0.001). These results generally confirm previous work showing litter
differences in aspects of play behaviour in both the pre and post-weaning period.
However, there was no consistency in litter differences between pre- and post
weaning periods in the categories of play behaviour with the exception of non
harmful fighting. We demonstrated a 'litter weaning effect' where litters respond
as a 'unit' to weaning in terms of their locomotory play behaviour. In general
these results add further support to the use of play as a sensitive welfare
indicator in neonatal pigs.
PMID- 29332979
TI - Standardized maximim D-optimal designs for enzyme kinetic inhibition models.
AB - Locally optimal designs for nonlinear models require a single set of nominal
values for the unknown parameters. An alternative is the maximin approach that
allows the user to specify a range of values for each parameter of interest.
However, the maximin approach is difficult because we first have to determine the
locally optimal design for each set of nominal values before maximin types of
optimal designs can be found via a nested optimization process. We show that
particle swarm optimization (PSO) techniques can solve such complex optimization
problems effectively. We demonstrate numerical results from PSO can help find,
for the first time, formulae for standardized maximin D-optimal designs for
nonlinear model with 3 or 4 parameters on the compact and nonnegative design
space. Additionally, we show locally and standardized maximin D-optimal designs
for inhibition models are not necessarily supported at a minimum number of
points. To facilitate use of such designs, we create a web-based tool for
practitioners to find tailor-made locally and standardized maximin optimal
designs.
PMID- 29332977
TI - The Role of Wnt Signalling in Angiogenesis.
AB - Angiogenesis is a normal biological process wherein new blood vessels form from
the growth of pre-existing blood vessels. Preventing angiogenesis in solid
tumours by targeting pro-angiogenic factors including vascular endothelial growth
factor (VEGF), angiopoietin-1 (Ang-1), basic fibroblast growth factor (bFGF),
hepatocyte growth factor, and platelet-derived growth factor (PDGF) is currently
under investigation for cancer treatment. Concurrently targeting the cell
signalling pathways involved in the transcriptional and post-translational
regulation of these factors may provide positive therapeutic results. One such
pathway is the Wnt signalling pathway. Wnt was first discovered in mice infected
with mouse mammary tumour virus, and has been crucial in improving our
understanding of oncogenesis and development. In this review, we summarise
molecular and cellular aspects of the importance of Wnt signalling to
angiogenesis, including beta-catenin-dependent mechanisms of angiogenic
promotion, as well as the study of Wnt antagonists, such as the secreted frizzled
related protein family (SFRPs) which have been shown to inhibit angiogenesis. The
growing understanding of the underlying complexity of the biochemical pathways
mediating angiogenesis is critical to the identification of new molecular targets
for therapeutic applications.
PMID- 29332980
TI - Domain-Specific Daily Hassles, Anxiety, and Delinquent Behaviors among Low
Income, Urban Youth.
AB - We studied contributions of domain-specific daily hassles to anxiety and
delinquency prior to and during the transition into middle (N = 186) or high
school (N = 167) in a sample of low-income, urban adolescents (93% African
American; 54% female) using a two-wave longitudinal design. Path models
controlling for baseline maladjustment and sex examined how hassles from parents,
peers, academics, and the neighborhood were associated with maladjustment once
youth had made the transition into a new school. Hassles with friends both prior
to and during the school transition mattered for older youth's maladjustment
only, whereas hassles with parents mattered for both older and younger youth.
Academic hassles only appeared to be problematic for younger youth. Neighborhood
hassles were associated in opposite ways with younger and older youth's
maladjustment. These findings suggest that both hassle type and the timing of the
school transition matter for youth maladjustment.
PMID- 29332981
TI - The Unique and Interactive Effects of Parent and School Bonds on Adolescent
Delinquency.
AB - Parent and school bonds are protective against delinquency. This study used
longitudinal data and multilevel Poisson regression models (MLM) to examine
unique and interactive associations of parent and school bonds on youth
delinquency in a sample of rural adolescents (n = 945; 84% White). We
investigated whether youth sex or transitioning to a new middle school moderated
the linkages between parent and school bonds and later delinquency. Results
indicated reduced delinquency was associated with positive parent and school
relationships. Parent and school bonds interacted such that linkages between
parent bonding and youth delinquency were stronger when youth also had high
school bonding - suggesting an additive effect. However, interactive effects were
only found when youth remained in the same school and became nonsignificant if
they transitioned to a new school. Findings support prior evidence that parent
and school bonds - and their interaction - play a unique role in reducing
delinquency.
PMID- 29332982
TI - Attachment, Social Information Processing, and Friendship Quality of Early
Adolescent Girls and Boys.
AB - Sixth-graders (N = 223; 109 girls) completed questionnaires assessing their
attachment security with their mothers and fathers, their social information
processing (SIP) when faced with ambiguously caused hypothetical negative events
involving a close friend, and the quality of the relationship with that friend.
Aspects of more maladaptive SIP were significantly related to lower levels of
security. The overall pattern of results did not provide strong evidence for
mediation, although boys' anger did tend to mediate the relation between
attachment to mother and friendship quality. Results are consistent with
attachment theory and suggest that the mechanisms connecting attachment and
friendship are specific with regard to the relationships boys and girls have with
their fathers and mothers.
PMID- 29332983
TI - Distinguishing Children Who Form New Best-Friendships from Those Who Do Not.
AB - Three groups were identified using best-friendship nominations at two time points
surrounding the transition to middle school (Time 1: Spring of 5th grade; Time 2:
Fall of 6th grade): (i) children who had no best-friendship at Time 1, but had a
best-friendship at Time 2 (best-friendship gain; N=109); (ii) children who had no
best-friendship at either Time 1 or 2 (chronically best-friendless; N=105); and
(iii) children with a best-friendship at both Times 1 and 2, but with different
peers at each time (best-friendship change; N=120). Peer nominations of social
behaviors and victimization were collected at Times 1 and 2. Findings suggest
that attraction to similar others, in addition to increased displays of prosocial
behaviors, facilitate the formation of new best-friendships for both initially
best-friendless and best-friended children.
PMID- 29332984
TI - White Matter Fiber-based Analysis of T1w/T2w Ratio Map.
AB - Purpose: To develop, test, evaluate and apply a novel tool for the white matter
fiber-based analysis of T1w/T2w ratio maps quantifying myelin content.
Background: The cerebral white matter in the human brain develops from a mostly
non-myelinated state to a nearly fully mature white matter myelination within the
first few years of life. High resolution T1w/T2w ratio maps are believed to be
effective in quantitatively estimating myelin content on a voxel-wise basis. We
propose the use of a fiber-tract-based analysis of such T1w/T2w ratio data, as it
allows us to separate fiber bundles that a common regional analysis imprecisely
groups together, and to associate effects to specific tracts rather than large,
broad regions. Methods: We developed an intuitive, open source tool to facilitate
such fiber-based studies of T1w/T2w ratio maps. Via its Graphical User Interface
(GUI) the tool is accessible to non-technical users. The framework uses
calibrated T1w/T2w ratio maps and a prior fiber atlas as an input to generate
profiles of T1w/T2w values. The resulting fiber profiles are used in a
statistical analysis that performs along-tract functional statistical analysis.
We applied this approach to a preliminary study of early brain development in
neonates. Results: We developed an open-source tool for the fiber based analysis
of T1w/T2w ratio maps and tested it in a study of brain development.
PMID- 29332985
TI - CIVILITY: Cloud based Interactive Visualization of Tractography Brain Connectome.
AB - Cloud based Interactive Visualization of Tractography Brain Connectome (CIVILITY)
is an interactive visualization tool of brain connectome in the cloud. This
application submits tasks to remote computing grids were the CIVILITY
tractography pipeline is deployed. The application will list the running tasks
for the user and once a task is completed the brain connectome is visualized
using Hierarchical Edge Bundling. The analysis pipeline uses FSL tools (bedpostx
and probtrackx2) to generate a triangular matrix indicating the connectivity
strength between different regions in the brain. This work is motivated by
medical applications in which expensive computational tasks such as brain
connectivity is needed and to provide a state of the art visualization tool of
Brain Connectome. This work does not contribute any novelty with respect to the
visualization methodology, is rather a new resource for the neuroimaging
community. This work is submitted to the SPIE Biomedical Applications in
Molecular, Structural, and Functional Imaging conference. The source code of this
application is available in NITRC.
PMID- 29332986
TI - FADTTSter: Accelerating Hypothesis Testing With Functional Analysis of Diffusion
Tensor Tract Statistics.
AB - Functional Analysis of Diffusion Tensor Tract Statistics (FADTTS) is a toolbox
for analysis of white matter (WM) fiber tracts. It allows associating diffusion
properties along major WM bundles with a set of covariates of interest, such as
age, diagnostic status and gender, and the structure of the variability of these
WM tract properties. However, to use this toolbox, a user must have an
intermediate knowledge in scripting languages (MATLAB). FADTTSter was created to
overcome this issue and make the statistical analysis accessible to any non
technical researcher. FADTTSter is actively being used by researchers at the
University of North Carolina. FADTTSter guides non-technical users through a
series of steps including quality control of subjects and fibers in order to
setup the necessary parameters to run FADTTS. Additionally, FADTTSter implements
interactive charts for FADTTS' outputs. This interactive chart enhances the
researcher experience and facilitates the analysis of the results. FADTTSter's
motivation is to improve usability and provide a new analysis tool to the
community that complements FADTTS. Ultimately, by enabling FADTTS to a broader
audience, FADTTSter seeks to accelerate hypothesis testing in neuroimaging
studies involving heterogeneous clinical data and diffusion tensor imaging. This
work is submitted to the Biomedical Applications in Molecular, Structural, and
Functional Imaging conference. The source code of this application is available
in NITRC.
PMID- 29332987
TI - Elevated Serum miR-7, miR-9, miR-122, and miR-141 Are Noninvasive Biomarkers of
Acute Pancreatitis.
AB - Background: It has been reported that several microRNAs (miRNAs), such as miR
141, miR-9, and miR-122, are involved in the regulation of pancreatitis-related
proteins or that their levels change in acute pancreatitis (AP) animal models.
However, the serum levels, as well as the clinical diagnostic and prognostic
values, of these miRNAs in AP patients remain unclear. Furthermore, as a pancreas
(islet) enriched miRNA, miR-7 was reported to be downregulated in AP patients,
which requires further verification. Methods: The levels of miR-7, miR-9, miR
122, and miR-141 were examined and compared using qRT-PCR among 80 severe AP
patients, 80 mild AP patients, and 74 healthy controls. Results: The serum levels
of these four miRNAs were increased markedly in the AP patients compared with the
controls, and these levels decreased significantly after effective therapy.
Particularly, the level of miR-7 was higher in severe AP patients than in mild AP
patients. ROC curve analysis demonstrated that four miRNAs could be used as
potential biomarkers for AP. Moreover, these miRNAs showed strong positive
correlations with CRP, which may be associated with inflammation. Conclusions:
The serum miR-7, miR-9, miR-122, and miR-141 levels were increased in AP
patients. These 4 miRNAs may represent diagnostic and prognostic biomarkers for
AP.
PMID- 29332988
TI - The Effect of Jaw Position on Perceptual and Acoustic Characteristics of Speech.
AB - Bite blocks are used to stabilize the jaw and to isolate tongue and lip movements
from that of the mandible during speech and nonspeech activities. Ten normally
speaking young adults produced sentences with an unconstrained jaw and with
unilateral placement of 2-mm and 5-mm bite blocks. Six listeners rated sentences
spoken without either bite block as the most natural sounding. Spectral
characteristics of /s/, /?/ and /t/ (sibilant frication and stop bursts) differed
significantly with than without bite blocks, such that mean spectral energy
decreased, and variation and skew of spectral energy increased. Spectral kurtosis
did not change for the group, but 2 participants exhibited highly kurtotic /s/
spectra without a bite block that normalized with bite blocks. The second formant
frequency for the high vowel /i/ was lower with bite blocks; there was no
systematic difference in F2 slope for diphthongs. Segmental and suprasegmental
timing of speech articulation was not affected significantly by these small bite
blocks. This study provides support for using small bite blocks to isolate the
tongue from the jaw without large effects on speech, but cautions that speech is
likely to sound less natural than when produced with an unconstrained jaw.
PMID- 29332989
TI - Art Therapy and Cognitive Processing Therapy for Combat-Related PTSD: A
Randomized Controlled Trial.
AB - This randomized controlled trial was designed to determine if art therapy in
conjunction with Cognitive Processing Therapy (CPT) was more effective for
reducing symptoms of combat posttraumatic stress disorder (PTSD) than CPT alone.
Veterans (N = 11) were randomized to receive either individual CPT, or individual
CPT in conjunction with individual art therapy. PTSD Checklist-Military Version
and Beck Depression Inventory-II scores improved with treatment in both groups
with no significant difference in improvement between the experimental and
control groups. Art therapy in conjunction with CPT was found to improve trauma
processing and veterans considered it to be an important part of their treatment
as it provided healthy distancing, enhanced trauma recall, and increased access
to emotions.
PMID- 29332990
TI - Order preservation of expected information content using Unscented Transform
approximation of multivariate prior distributions in HIV 2-LTR experiment design.
AB - Numerical computation of the expected information content of a prospective
experimental design is computationally expensive, requiring calculating the
Kullback-Leibler divergence of the posterior distribution from the prior for
simulated data from a large sample of points from the prior distribution. In this
work, we investigate whether the Unscented Transform (UT) of the prior
distribution can provide an adequate estimate of the expected information content
in the context of experiment design for a previously validated HIV-1 2-LTR model.
Three different schedules with evenly distributed time points have been used to
generate the experimental data along with the incorporation of qPCR noise for the
study. The UT shows promise in estimating information content by preserving the
optimal ordering of 2-LTR sample collection schedules, when compared to
completely stochastic sampling from the underlying multivariate distributions.
PMID- 29332991
TI - Prospective HIV Clinical Trial Comparison by Expected Kullback-Leibler
Divergence.
AB - The sample frequency and volume of blood that can be drawn from a single patient
is meticulously restricted under the human subject protection protocols
established by an institutional review board (IRB). Consequently, the amount of
samples that can be taken during a particular experiment is limited. In order to
ensure an effective experiment design, considerations must be taken choosing when
to take patient samples. A validated model of HIV-1 viral replication and 2-LTR
production is exploited to find sub-optimal sampling schedules that maximize
information content of the experiment outcome. This is done through a Forward
Stepwise Regression (FSR) process with Kullback Liebler Divergence (KLD) as a
selection criterion. Suboptimal schedules are found for an experiment taking four
sample points over a possible span of 20 weeks. All schedules found with the FSR
process contain significantly more information than both a uniform schedule and a
schedule used in a previous experiment with 4 sample points. This work
demonstrates the advantages of using KLD as a tool in the experiment design
process to increase information content.
PMID- 29332992
TI - Experiment Design for Early Molecular Events in HIV Infection.
AB - The recent introduction of integrase inhibitors to the HIV antiviral repertoire
permits us to create in vitro experiments that reliably terminate HIV infection
at the point of chromosomal integration. This allows us to isolate the dynamics
of a single round of infection, without needing to account for the influence of
multiple overlapping rounds of infection. By measuring the various nucleic acid
concentrations in a population of infected target cells at multiple time points,
we can infer the rates of these molecular events with great accuracy, which
allows us to compare the rates between target cells with different functional
phenotypes. This information will help in understanding the behavior of the
various populations of reservoir cells such as active and quiescent T-cells which
maintain HIV infection in treated patients. In this paper, we introduce a family
of models of the early molecular events in HIV infection, with either linear
dynamics or age-structured delays at each step. We introduce an experimental
design metric based on the delta AIC (Akaike Information Criteria) between a
model fit for simulated data from a matching model vs a mismatched model, which
allows us to determine a candidate experiment design's ability to discriminate
between models. Using parameters values drawn from experimentally-derived priors
corrupted with appropriate measurement noise, we confirm that a proposed sampling
schedule at different time points allows us to consistently discriminate between
candidate models.
PMID- 29332993
TI - Composition of the C6+ Fraction of Natural Gas by Multiple Porous Layer Open
Tubular Capillaries Maintained at Low Temperatures.
AB - As the sources of natural gas become more diverse, the trace constituents of the
C6+ fraction are of increasing interest. Analysis of fuel gas (including natural
gas) for compounds with more than 6 carbon atoms (the C6+ fraction) has
historically been complex and expensive. Hence, this is a procedure that is used
most often in troubleshooting rather than for day-to-day operations. The C6+
fraction affects gas quality issues and safety considerations such as anomalies
associated with odorization. Recent advances in dynamic headspace vapor
collection can be applied to this analysis and provide a faster, less complex
alternative for compositional determination of the C6+ fraction of natural gas.
Porous layer open tubular capillaries maintained at low temperatures (PLOT-cryo)
form the basis of a dynamic headspace sampling method that was developed at NIST
initially for explosives in 2009. This method has been recently advanced by the
combining of multiple PLOT capillary traps into one "bundle," or wafer, resulting
in a device that allows the rapid trapping of relatively large amounts of
analyte. In this study, natural gas analytes were collected by flowing natural
gas from the laboratory (gas out of the wall) or a prepared surrogate gas flowing
through a chilled wafer. The analytes were then removed from the PLOT-cryo wafer
by thermal desorption and subsequent flushing of the wafer with helium. Gas
chromatography (GC) with mass spectrometry (MS) was then used to identify the
analytes.
PMID- 29332994
TI - Application of the Advanced Distillation Curve Method to the Comparison of Diesel
Fuel Oxygenates: 2,5,7,10-Tetraoxaundecane (TOU), 2,4,7,9-Tetraoxadecane (TOD),
and Ethanol/Fatty Acid Methyl Ester (FAME) Mixtures.
AB - Although they are amongst the most efficient engine types, compression-ignition
engines have difficulties achieving acceptable particulate emission and NOx
formation. Indeed, catalytic after-treatment of diesel exhaust has become common
and current efforts to reformulate diesel fuels have concentrated on the
incorporation of oxygenates into the fuel. One of the best ways to characterize
changes to a fuel upon the addition of oxygenates is to examine the volatility of
the fuel mixture. In this paper, we present the volatility, as measured by the
advanced distillation curve method, of a prototype diesel fuel with novel diesel
fuel oxygenates: 2,5,7,10-tetraoxaundecane (TOU), 2,4,7,9-tetraoxadecane (TOD),
and ethanol/fatty acid methyl ester (FAME) mixtures. We present the results for
the initial boiling behavior, the distillation curve temperatures, and track the
oxygenates throughout the distillations. These diesel fuel blends have several
interesting thermodynamic properties that have not been seen in our previous
oxygenate studies. Ethanol reduces the temperatures observed early in the
distillation (near ethanol's boiling temperature). After these early distillation
points (once the ethanol has distilled out), B100 has the greatest impact on the
remaining distillation curve and shifts the curve to higher temperatures than
what is seen for diesel fuel/ethanol blends. In fact, for the 15% B100 mixture
most of the distillation curve reaches temperatures higher than those seen diesel
fuel alone. In addition, blends with TOU and TOD also exhibited uncommon
characteristics. These additives are unusual because they distill over most the
distillation curve (up to 70%). The effects of this can be seen both in
histograms of oxygenate concentration in the distillate cuts and in the
distillation curves. Our purpose for studying these oxygenate blends is
consistent with our vision for replacing fit-for-purpose properties with
fundamental properties to enable the development of equations of state that can
describe the thermodynamic properties of complex mixtures, with specific
attention paid to additives.
PMID- 29332995
TI - On the Functional Form of Temporal Discounting: An Optimized Adaptive Test.
AB - The tendency to discount the value of future rewards has become one of the best
studied constructs in the behavioral sciences. Although hyperbolic discounting
remains the dominant quantitative characterization of this phenomenon, a variety
of models have been proposed and consensus around the one that most accurately
describes behavior has been elusive. To help bring some clarity to this issue, we
propose an Adaptive Design Optimization (ADO) method for fitting and comparing
models of temporal discounting. We then conduct an ADO experiment aimed at
discriminating among six popular models of temporal discounting. Rather than
supporting a single underlying model, our results show that each model is
inadequate in some way to describe the full range of behavior exhibited across
subjects. The precision of results provided by ADO further identify specific
properties of models, such as accommodating both increasing and decreasing
impatience, that are mandatory to describe temporal discounting broadly.
PMID- 29332996
TI - Optimal Population and Exhaustible Resource Constraints.
AB - A large literature considers the optimal size and growth rate of the human
population, trading off the utility value of additional people with the costs of
a larger population. In this literature, an important parameter is the social
weight placed on population size; a standard result is that a planner with a
larger weight on population chooses larger population levels and growth rates. We
demonstrate that this result is conditionally overturned when an exhaustible
resource constraint is introduced: if the discount rate is small enough, the
optimal population today decreases with the welfare weight on population size.
That is, a more total-utilitarian social planner could prefer a smaller
population today than a more average-utilitarian social planner. We also present
a numerical illustration applied to the case of climate change, where we show
that under plausible real-world parameter values, our result matters for the
direction and magnitude of optimal population policy.
PMID- 29332997
TI - EPR UNIFORM FIELD SIGNAL ENHANCEMENT BY DIELECTRIC TUBES IN CAVITIES.
AB - The dielectric tube resonator (DTR) for EPR spectroscopy is introduced. It is
defined as a metallic cylindrical TE011 microwave cavity that contains a
dielectric tube centered on the axis of the cylinder. Contour plots of dimensions
of the metallic cylinder to achieve resonance at 9.5 GHz are shown for quartz,
sapphire, and rutile tubes as a function of wall thickness and average radius.
These contour plots were developed using analytical equations and confirmed by
finite element modeling. They can be used in two ways: design of the metallic
cylinder for use at 9.5 GHz that incorporates a readily available tube such as a
sapphire tube intended for NMR, or design of a custom procured tube for optimized
performance for specific sample-size constraints. The charts extend to the
limiting condition where the dielectric fills the tube. However, the structure at
this limit is not a dielectric resonator due to the metal wall and does not
radiate. In addition, the uniform field (UF) DTR is introduced. Development of
the UF resonator starting with a dielectric tube resonator is shown. The diameter
of the tube remains constant along the cavity axis, and the diameter of the
cylindrical metallic enclosure increases at the ends of the cavity to satisfy the
uniform field condition. This structure has advantages over the previously
developed UF TE011 resonators: higher resonator efficiency parameter Lambda,
convenient overall size when using sapphire tubes, and higher quality data for
small samples. The DTR and UF DTR structures fill the gap between free space and
dielectric resonator limits in a continuous manner.
PMID- 29332998
TI - High-pressure EPR spectroscopy studies of the E. coli lipopolysaccharide
transport proteins LptA and LptC.
AB - The use of pressure is an advantageous approach to the study of protein structure
and dynamics because it can shift the equilibrium populations of protein
conformations toward higher energy states that are not of sufficient population
to be observable at atmospheric pressure. Recently, the Hubbell group at the
University of California, Los Angeles, reintroduced the application of high
pressure to the study of proteins by electron paramagnetic resonance (EPR)
spectroscopy. This methodology is possible using X-band EPR spectroscopy due to
advances in pressure intensifiers, sample cells, and resonators. In addition to
the commercial availability of the pressure generation and sample cells by
Pressure Biosciences Inc., a five-loop-four-gap resonator required for the
initial high pressure EPR spectroscopy experiments by the Hubbell group, and
those reported here, was designed by James S. Hyde and built and modified at the
National Biomedical EPR Center. With these technological advances, we determined
the effect of pressure on the essential periplasmic lipopolysaccharide (LPS)
transport protein from Escherichia coli, LptA, and one of its binding partners,
LptC. LptA unfolds from the N-terminus to the C-terminus, binding of LPS does not
appreciably stabilize the protein under pressure, and monomeric LptA unfolds
somewhat more readily than oligomeric LptA upon pressurization to 2 kbar. LptC
exhibits a fold and relative lack of stability upon LPS binding similar to LptA,
yet adopts an altered, likely monomeric, folded conformation under pressure with
only its C-terminus unraveling. The pressure-induced changes likely correlate
with functional changes associated with binding and transport of LPS.
PMID- 29332999
TI - An integrated electrolysis - electrospray - ionization antimicrobial platform
using Engineered Water Nanostructures (EWNS) for food safety applications.
AB - Engineered water nanostructures (EWNS) synthesized utilizing electrospray and
ionization of water, have been, recently, shown to be an effective, green,
antimicrobial platform for surface and air disinfection, where reactive oxygen
species (ROS), generated and encapsulated within the particles during synthesis,
were found to be the main inactivation mechanism. Herein, the antimicrobial
potency of the EWNS was further enhanced by integrating electrolysis,
electrospray and ionization of de-ionized water in the EWNS synthesis process.
Detailed physicochemical characterization of these enhanced EWNS (eEWNS) was
performed using state-of-the-art analytical methods and has shown that, while
both size and charge remain similar to the EWNS (mean diameter of 13 nm and
charge of 13 electrons), they possess a three times higher ROS content. The
increase of the ROS content as a result of the addition of the electrolysis step
before electrospray and ionization led to an increased antimicrobial ability as
verified by E. coli inactivation studies using stainless steel coupons. It was
shown that a 45-minute exposure to eEWNS resulted in a 4-log reduction as opposed
to a 1.9-log reduction when exposed to EWNS. In addition, the eEWNS were assessed
for their potency to inactivate natural microbiota (total viable and yeast and
mold counts), as well as, inoculated E.coli on the surface of fresh organic
blackberries. The results showed a 97% (1.5-log) inactivation of the total viable
count, a 99% (2-log) reduction in the yeast and mold count and a 2.5-log
reduction of the inoculated E.coli after 45 minutes of exposure, without any
visual changes to the fruit. This enhanced antimicrobial activity further
underpins the EWNS platform as an effective, dry and chemical free approach
suitable for a variety of food safety applications and could be ideal for
delicate fresh produce that cannot withstand the classical, wet disinfection
treatments.
PMID- 29333000
TI - Distributions of emissions intensity for individual beef cattle reared on pasture
based production systems.
AB - Life Cycle Assessment (LCA) of livestock production systems is often based on
inventory data for farms typical of a study region. As information on individual
animals is often unavailable, livestock data may already be aggregated at the
time of inventory analysis, both across individual animals and across seasons.
Even though various computational tools exist to consider the effect of genetic
and seasonal variabilities in livestock-originated emissions intensity, the
degree to which these methods can address the bias suffered by representative
animal approaches is not well-understood. Using detailed on-farm data collected
on the North Wyke Farm Platform (NWFP) in Devon, UK, this paper proposes a novel
approach of life cycle impact assessment that complements the existing LCA
methodology. Field data, such as forage quality and animal performance, were
measured at high spatial and temporal resolutions and directly transferred into
LCA processes. This approach has enabled derivation of emissions intensity for
each individual animal and, by extension, its intra-farm distribution, providing
a step towards reducing uncertainty related to agricultural production inherent
in LCA studies for food. Depending on pasture management strategies, the total
emissions intensity estimated by the proposed method was higher than the
equivalent value recalculated using a representative animal approach by 0.9-1.7
kg CO2-eq/kg liveweight gain, or up to 10% of system-wide emissions. This finding
suggests that emissions intensity values derived by the latter technique may be
underestimated due to insufficient consideration given to poorly performing
animals, whose emissions becomes exponentially greater as average daily gain
decreases. Strategies to mitigate life-cycle environmental impacts of pasture
based beef productions systems are also discussed.
PMID- 29333001
TI - Evidence for the Involvement of Lipid Rafts and Plasma Membrane Sphingolipid
Hydrolases in Pseudomonas aeruginosa Infection of Cystic Fibrosis Bronchial
Epithelial Cells.
AB - Cystic fibrosis (CF) is the most common autosomal genetic recessive disease
caused by mutations of gene encoding for the cystic fibrosis transmembrane
conductance regulator. Patients with CF display a wide spectrum of symptoms, the
most severe being chronic lung infection and inflammation, which lead to onset of
cystic fibrosis lung disease. Several studies indicate that sphingolipids play a
regulatory role in airway inflammation. The inhibition and downregulation of
GBA2, the enzyme catabolizing glucosylceramide to ceramide, are associated with a
significant reduction of IL-8 production in CF bronchial epithelial cells.
Herein, we demonstrate that GBA2 plays a role in the proinflammatory state
characterizing CF cells. We also report for the first time that Pseudomonas
aeruginosa infection causes a recruitment of plasma membrane-associated
glycosphingolipid hydrolases into lipid rafts of CuFi-1-infected cells. This
reorganization of cell membrane may be responsible for activation of a signaling
cascade, culminating in aberrant inflammatory response in CF bronchial epithelial
cells upon bacterial infection. Taken together, the presented data further
support the role of sphingolipids and their metabolic enzymes in controlling the
inflammatory response in CF.
PMID- 29333003
TI - Histopathological study of gallbladder carcinoma and its mimics with role of
carcinoembryonic antigen immunomarker in resolving diagnostic difficulties.
AB - Background: Gallbladder carcinoma (GBC) sometimes presents with nonspecific
signs, without forming a mass, mimicking benign gallbladder (GB) diseases. On the
contrary, benign GB diseases may mimic GBC. Material and Methods: We
retrospectively reviewed 107 cases over a period of 3 years (May 2012-April
2015), which included 41 review cases and 66 departmental cases. Carcinoembryonic
antigen (CEA) immunomarker expression was done. Results: In 27 of the 41 review
cases, the diagnoses were benign diseases of GB associated with mild-to-moderate
dysplasia of mucosal glands; however, after review in our department, it was
found that of these 27 cases, nine cases were actually well-differentiated
adenocarcinoma of GB with diffuse CEA expression and were mis diagnosed as benign
diseases of GB with dysplasia. In 32 out of 66 departmental cases, initial
histopathological diagnoses were benign diseases of GB associated with dysplastic
mucosal glands. After CEA staining, 11 out of these 32 cases turned out to be
adenocarcinoma of the GB. Among the rest 34 (34/66) departmental primary GBC
cases, no CEA expression was seen in six cases, focal expression was seen in 12
cases, and diffuse expression was seen in 16 cases. No diffuse CEA expression was
seen in benign diseases of the GB with dysplasia. Conclusion: GBC sometimes may
not be diagnosed radiologically and grossly as it often presents without any mass
and specific signs, which lead to under diagnosis. Some benign cases may mimic
GBC and may complicate histological diagnosis. CEA expression may aid as an
additional diagnostic aid in resolving diagnostic dilemmas.
PMID- 29333004
TI - DROSHA rs642321 Polymorphism Influence Susceptibility to Childhood Acute
Lymphoblastic Leukemia: A Preliminary Report.
AB - Introduction: It has been well known that the microRNA biogenesis is involved in
the pathogenesis of various diseases. We investigated the possible association
between DROSHA rs642321 variant and risk of acute lymphocytic leukemia (ALL).
Materials and Methods: We genotyped 75 children diagnosed with ALL and 115 age-
and sex-matched children with no history of cancer of any type (as the control
group) by the tetra amplification refractory mutation system-polymerase chain
reaction. Results: We found that DROSHA rs642321 C > T variant significantly
decreased the risk of ALL in codominant (TT vs. CC: odds ratio [OR] = 0.33, 95%
confidence interval [CI] = 0.14-0.80, P = 0.020) and dominant (TT + CT vs. CC: OR
= 0.51, 95% CI = 0.27-0.94, P = 0.037) inheritance model tested. The rs642321 T
allele was associated with protective against ALL (OR = 0.58, 95% CI = 0.38-0.88,
P = 0.011) in comparison with C allele. Conclusion: The study findings revealed
that DROSHA rs642321 variant decreased the risk of pediatrics ALL in an Iranian
population. Larger sample sizes with different ethnicities are needed to validate
our findings.
PMID- 29333005
TI - Prognostic Factors and Survival Outcomes of Intracranial Ependymoma Treated with
Multimodality Approach.
AB - Objectives: We aimed to analyze treatment outcomes of intracranial ependymoma
(ICE) treated at our institute with multimodality approach. Materials and
Methods: Demography, treatment details, and survival data of 40 patients (2005
2012) were collected in a predesigned pro forma. Kaplan Meier method was used to
analyze disease-free survival (DFS) and the impact of prognostic factors was
determined using univariate analysis (log-rank test). Multivariate analysis was
performed using Cox-proportional hazard model. SPSS version 21.0 was used for all
statistical analysis. Results: Male:female ratio was 29:11. Gross total
resection: subtotal resection or less was 42.5%: 57.5%. A total of 16 patients
(40%) had anaplastic histology. All except two patients received adjuvant
radiotherapy. Four patients received concurrent chemotherapy (temozolomide [TMZ])
and 10 patients received adjuvant chemotherapy (6 carboplatin plus etoposide; 4
TMZ). Median follows up was 18 months (2-60 months). Median DFS for the entire
cohort was 22.42 months. The estimated 1, 2, and 3 years DFS was found to be
58.5%, 41%, and 30.7%, respectively. On univariate analysis, patients receiving
higher radiation dose (56 Gray vs. 60 Gray; hazard ratio [HR] 0.366; 95%
confidence interval [CI] 0.142-0.9553; P = 0.02) and lower MIB labeling index
(<20 vs. >=20; HR 0.238; 95% CI 0.092-0.617; P = 0.001) had a better DFS. Higher
radiation dose continued to be an independent prognostic factor on multivariate
analysis (HR 0.212; 95% CI 0.064-0.856; P = 0.03). Conclusion: ICE has guarded
prognosis. Adjuvant radiotherapy to a higher radiation dose improves survival.
Higher MIB labeling index connotes a dismal survival despite the use of
radiotherapy and chemotherapy.
PMID- 29333002
TI - S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory Signaling.
AB - Sphingosine-1-phosphate (S1P) is a potent lipid signaling molecule that regulates
pleiotropic biological functions including cell migration, survival,
angiogenesis, immune cell trafficking, inflammation, and carcinogenesis. It acts
as a ligand for a family of cell surface receptors. S1P concentrations are high
in blood and lymph but low in tissues, especially the thymus and lymphoid organs.
S1P chemotactic gradients are essential for lymphocyte egress and other aspects
of physiological cell trafficking. S1P is irreversibly degraded by S1P lyase
(SPL). SPL regulates lymphocyte trafficking, inflammation and other physiological
and pathological processes. For example, SPL located in thymic dendritic cells
acts as a metabolic gatekeeper that controls the normal egress of mature T
lymphocytes from the thymus into the circulation, whereas SPL deficiency in gut
epithelial cells promotes colitis and colitis-associated carcinogenesis (CAC).
Recently, we identified a complex syndrome comprised of nephrosis, adrenal
insufficiency, and immunological defects caused by inherited mutations in human
SGPL1, the gene encoding SPL. In the present article, we review current evidence
supporting the role of SPL in thymic egress, inflammation, and cancer. Lastly, we
summarize recent progress in understanding other SPL functions, its role in
inherited disease, and SPL targeting for therapeutic purposes.
PMID- 29333006
TI - Rational Use of Imaging to Stage Breast Cancer: Evidences for a Selective
Approach.
AB - Introduction: Staging investigations at diagnosis are customary to accurately
assign a clinical stage before therapy. The practice of routine imaging in
patients asymptomatic for metastasis is not recommended but widely adopted. This
study was done to reexamine the basis behind guideline recommendations and to
identify the factors predictive of asymptomatic metastasis. Methods: Oncology
records of 200 breast cancer patients in clinical Stages I-III at diagnosis were
prospectively reviewed. Baseline demographic information, tumor characteristics,
and pathological data including molecular typing were collected. The prevalence
of metastasis deduced and accuracy of bone scan, chest X-ray (CXR), liver
ultrasound, and computed tomography (CT) chest analyzed. Patient and tumor
characteristics predictive of asymptomatic metastasis tested for significance
using appropriate statistical tests. Results: The prevalence of asymptomatic
metastasis was 13.5%. Bone lesions (8%) were the most common metastatic site
followed by lungs (7%) and liver (1%). Sensitivity, specificity, positive- and
negative-predictive values of bone scans and CT chest were 100%, 97%, 74%, 100%,
and 92%, 99%, 87, 3%, 99.4%, respectively. The above values for ultrasound
abdomen and CXRs were 100%, 99%, 93%, 100% and 21%, 94%, 20%, 94%, respectively.
Tumor size (P = 0.001), tumor Stage T1/T2 versus T3/T4 (P = 0.0002), nodal stages
N0/N1 versus N2/N3 (P = 0.001), high histological Grade G I versus GII/GIII (P =
0.0001) and molecular types were strongly predictive of metastatic disease.
Conclusion: The routine use of imaging to detect distant metastasis in
asymptomatic patients is not recommended in newly diagnosed breast cancer. A
selective approach may be adopted in individuals with tumor more than 5 cm,
advanced nodal disease, higher histological grade, and aggressive molecular
types.
PMID- 29333007
TI - Utility of Cluster of Differentiation 5 and Cluster of Differentiation 117
Immunoprofile in Distinguishing Thymic Carcinoma from Pulmonary Squamous Cell
Carcinoma: A Study on 1800 Nonsmall Cell Lung Cancer Cases.
AB - Background: Mediastinum harbors a mixed bag of neoplastic lesions with varied
therapeutic and prognostic implications. Distinguishing pulmonary squamous cell
carcinoma from thymic carcinoma is a challenging task owing to rather nonspecific
clinicoradiological features and a considerable overlap in histomorphological
features. Thus, we evaluated the diagnostic utility of cluster of differentiation
5 (CD5) and CD117 immunohistochemical markers in distinguishing these tumors.
Materials and Methods: The archives of department of histopathology were
retrospectively reviewed from June 2012 to May 2016. Formalin-fixed paraffin
embedded blocks of 1800 cases diagnosed as nonsmall cell lung carcinoma were
retrieved, and immunohistochemical expression of CD5 and CD117 was evaluated in
these cases. Results: Adenocarcinoma (980; 54.44%) was the most common
histological subtype of lung carcinoma observed in our study. CD117 was positive
in 171 out of 1800 cases (9.5%) of which 120 cases (70.17%) were adenocarcinoma,
followed by 40 cases (23.4%) of squamous cell carcinoma. Immunoreactivity for CD5
was observed in 209 cases (11.61%), 200 (95.7%) cases of which were diagnosed as
adenocarcinoma. None of the cases diagnosed as squamous cell carcinoma on
histomorphology showed CD5 immunoexpression. Conclusion: While thymic squamous
cell carcinomas are well known for CD5 and CD117 coexpression, none of the cases
of squamous cell carcinoma arising in lung express CD5. These markers are a
diagnostic tool to distinguish a primary lung squamous cell carcinoma from thymic
carcinoma, particularly in the setting of a central pulmonary lesion with
mediastinal involvement.
PMID- 29333009
TI - Peripheral and Central Giant Cell Lesions in Children: Institutional Experience
at Subharti Dental College and Hospital.
AB - Introduction: Giant cell lesions (GCG) are a group of varied lesions that contain
a multitude of multinucleated, osteoclast like giant cells within connective
tissue stroma. These include giant cell granulomas which may be central (CGCG),
if they lie within the jaw bone, or, peripheral (PGCG) if they lie within the
soft tissue. Giant cell granulomas comprised 9.29% of all oral lesions. This case
series comprises of 5 giant cell lesions in children between the ages of 4 to 12
years. Materials and Methods: A retrospective analysis was conducted of all
patients who were diagnosed with giant cell lesions and treated over a period of
10 years (from August 2004 to August 2014) at Subharti Dental College and
Hospital, Meerut, India. Results: A total of 5 giant cell lesions were identified
in this case series, of which 2 cases were diagnosed as PGCG and 3 cases as CGCG.
Surgical excision and curettage was performed for 2 peripheral lesions under
local anesthesia while 1 central lesion was excised under general anesthesia. Two
central lesions were treated with a non-surgical approach using intralesional
corticosteroid. Conclusion: Our experience suggests that a correct diagnosis and
complete surgical excision with curettage is effective in complete management of
oral giant cell lesions in the pediatric age group.
PMID- 29333008
TI - Metabolic Syndrome and Breast Cancer Risk.
AB - Objective: The study was meant to estimate the prevalence of metabolic syndrome
in patients with breast cancer and to establish its role as an independent risk
factor on occurrence of breast cancer. Materials and Methods: Fifty women aged
between 40 and 80 years with breast cancer and fifty controls of similar age were
assessed for metabolic syndrome prevalence and breast cancer risk factors,
including age at menarche, reproductive status, live births, breastfeeding, and
family history of breast cancer, age at diagnosis of breast cancer, body mass
index, and metabolic syndrome parameters. Results: Metabolic syndrome prevalence
was found in 40.0% of breast cancer patients, and 18.0% of those in control group
(P = 0.02). An independent and positive association was seen between metabolic
syndrome and breast cancer risk (odds ratio = 3.037; 95% confidence interval
1.214-7.597). Conclusions: Metabolic syndrome is more prevalent in breast cancer
patients and is an independent risk factor for breast cancer.
PMID- 29333010
TI - Sinusoidal Obstruction Syndrome during Treatment for Wilms' Tumor: A Life
threatening Complication.
AB - Context: Survival rates exceed 90% in Wilms' tumor (WT). Actinomycin-D (ACT-D)
which is indispensable in the management of WT is associated with the development
of sinusoidal obstruction syndrome (SOS), a potentially fatal complication. Aims:
The aim is to study the presentation, management, and outcome of SOS complicating
ACT-D administration in WT. Settings and Design: Retrospective file review
conducted in a Pediatric Hematology-Oncology unit. Materials and Methods:
Patients diagnosed and treated for WT from January 2012 to December 2015 were
analyzed. SOS was diagnosed clinically, based on McDonalds criteria, requiring
two of the following: jaundice, hepatomegaly and/or right upper quadrant pain,
weight gain with or without ascites. Results: Of 104 patients treated, SOS
occurred in 5 (4.8%). Age: 6 months to 5 years, 3 were girls. Tumor involved left
kidney in 3, right in 1 and a horseshoe kidney in 1. Histopathology was
consistent with WT in 4 and clear cell sarcoma kidney in 1. One had pulmonary
metastases. Three developed SOS preoperatively and two during adjuvant
chemotherapy. None received radiotherapy. Clinical manifestations comprised of
jaundice, hepatomegaly, ascites/weight gain, respiratory distress, hypotension,
and encephalopathy. Laboratory findings included thrombocytopenia, elevated serum
transaminases, and coagulopathy. Treatment included fluid restriction, broad
spectrum antibiotics, and transfusional support. Two children received N-acetyl
cysteine infusion. Defibrotide was administered to two patients. Four recovered
and one succumbed to multi-organ failure. Two patients were safely re-challenged
with 50% doses of ACT-D. Conclusions: SOS is a clinical diagnosis. Systematic
supportive care can enable complete recovery. Under close monitoring, re
challenge of ACT-D can be performed in gradually escalating doses.
PMID- 29333011
TI - Oral Verrucous Carcinoma: Ten Year Experience from a Tertiary Care Hospital in
India.
AB - Background: Verrucous carcinoma of the oral cavity (OVC) is an uncommon variant
of oral squamous cell carcinoma (OSCC). The clinical presentation and surgical
outcomes of OVC are unique; however, the management protocols for OVC are largely
extrapolated from OSCC. Objectives: The aim is to study the clinical,
histopathological demographics, and outcome of OVC at a tertiary care referral
hospital in South India. To study the need for lymph node dissection and the role
of adjuvant therapy for close resection margins. Materials and Methods: A
retrospective review of all patients diagnosed to have OVC between January 2005
and April 2015 was undertaken. Data were collected from hospital records and
telephonic interview when possible. Results: Thirty patients were diagnosed to
have OVC. The most common site of the presentation was the buccal mucosa. Twenty
three patients had wide local excision of the primary tumor and seven patients
had neck dissection as well. None of the patients who underwent neck dissection
had node-positive disease pathologically. The margins were considered close in
nine patients, only one of these patients received adjuvant radiation therapy;
despite among the patients with close resection margins, there was no recurrence
or disease-related mortality. Among the thirty patients, there was only one
patient who had recurred locally and there was no disease associated mortality.
Conclusions: OVC is a unique variant of OSCC which has a good prognosis. Routine
lymphadenectomy can be avoided.
PMID- 29333012
TI - Squamous Cell Carcinoma Lung with Skeletal Muscle Involvement: A 8-year Study of
a Tertiary Care Hospital in Kashmir.
AB - Aims: Lung cancer is the most common malignancy throughout the world. Nonsmall
cell lung cancer (NSCLC) is the most common type, and squamous cell type is most
common in India. Mostly, patients present with chest-related symptoms and signs.
Isolated skeletal muscle metastasis (ISMM) is rarely seen. The aim was to see
muscle metastasis and its prognosis. Materials and Methods: We are presenting our
data of 8 years about this common malignancy with relation to muscle metastasis,
either alone or with other system metastasis. Results: Muscle metastasis is seen
1.5% of patients, with male: female of 8:1. Overall median survival was 15 months
and progression-free survival was 12 months. Conclusion: One peculiarity seen was
ISMM with no pulmonary system and severe paraneoplastic hypercalcemia. Local
therapy may be having an impact on overall survival in metachronous muscle
involvement.
PMID- 29333013
TI - Comparative Study of Imprint Cytology and Histopathology of Soft Tissue Tumors.
AB - Background: The components of soft tissue are fibroblasts, collagen, vascular
structures, fatty tissue, skeletal muscles, smooth muscles, and neural tissue.
The real incidence of soft tissue tumors (STTs) is difficult to estimate because
most of them are benign (Benign: Malignant-100:1). Aims: The aim of the present
study was undertaken to note the patterns of presentation of patients with STTs
and to evaluate the findings of imprint cytology (IC) and histopathological
examination (HPE) of STTs. Materials and Methods: The present study was
undertaken for 1 year. A total of 41 patients with clinically and radiologically
diagnosed STTs were included in the study. Following surgery, imprint smear was
taken for each tumor, before delivering the tissue to 10% formalin. HPE was
subsequently performed. Results: The age of the patients ranged from 4 months to
80 years with a mean of 35.6 +/- 17.5 years. The ratio of males to females was
1.05:1. HPE revealed that 21 (51.2%) tumors were benign and 20 (48.8%) malignant.
Imprint smears revealed 16 (39%) tumors to be benign and 20 (48.8%) malignant. IC
was inconclusive in 5 (12.2%) cases. The sensitivity of IC was found to be 89.5%
and specificity 82.35%. The positive predictive value of IC was 85%. The accuracy
of IC for diagnosis of both benign and malignant tumors was found to be 75%.
Conclusion: IC of STTs is a rapid and simple method of intraoperative diagnosis,
and it can serve as a viable alternative to frozen section biopsy, particularly
in rural settings.
PMID- 29333014
TI - Is Colorectal Cancer in Young (<40 Years) Different from those in the Elderly
(>40 Years): Experience from a Regional Care Center.
AB - Background: Colorectal cancer (CRC) is considered a disease of elderly. There has
been a steady decrease in the incidence in those aged >50 years, with an alarming
increase noted in adults aged <50 years. Subjects and Methods: We retrospectively
analyzed 89 patients diagnosed with CRC aged <40 years between the years 2010 and
2014. Their clinical profile, treatment, and outcomes were studied. Results: The
median age was 33 years with a male preponderance (56.2%). Most common symptoms
were lower gastrointestinal bleed (48.3%) followed by abdominal pain (46.1%).
Most common sites were rectum (50.6%) followed by colon. Histology in all was
adenocarcinoma. Most tumors were moderately differentiated (54%) and were stage 4
(36%). Most common sites of metastases were liver (46.9%) followed by peritoneum
and ovaries. Majority underwent surgery with adjuvant chemotherapy, with/without
radiotherapy. Chemotherapy was administered in 70 patients, majority receiving
FOLFOX-4 regimen (88.6%). Median survival was 23 months. Survival in early
stage[1],[2] was significantly higher than in advanced stages (3 and above), 34
and 19 months (P = 0.0287), in those aged >40 years compared to <40-35 versus 23
months (P = 0.0029), nonmetastatic compared to metastatic disease - 26 versus 14
months (P = 0.00196), and females compared to males - 26 and 18 months (P =
0.0242). There was no significant difference in survival with respect to tumor
grade or site of metastases (hepatic versus extrahepatic). Conclusions:
Colorectal carcinoma in young seems to be an emerging problem in India. Any young
patient presenting with symptoms suggestive of a colonic malignancy should be
evaluated promptly and treated aggressively.
PMID- 29333015
TI - A Profile of Pediatric Solid Tumors: A Single Institution Experience in Kashmir.
AB - Aims: The purpose of this retroprospective study was to study the epidemiological
characteristics and outcomes of children with solid tumors at our institution.
Subjects and Methods: Three hundred and three pediatrics patients registered at
Regional Cancer Centre (RCC), Sher-i-Kashmir Institute of Medical Sciences
(SKIMS), Srinagar, Kashmir, between January 2008 and June 2014, were analyzed
with regard to demographic status, presenting complaints, investigations,
treatment, morbidity, and outcomes. Standard statistical methods were used for
analysis. Results: Among 19,880 patients registered at RCC, SKIMS from January
2008 till June 2014, 986 (4.9%) were of pediatric age group. Of these, 303
(30.7%) patients had pediatric solid tumors. The male-to-female ratio was 1.04,
there were no infants (up to 27 days), 6% were infants and toddlers (28 days-23
months), 39% were children (2-11 years), and 55% were adolescents (12-19 years).
There were 86% rural patients and 14% urban patients. Most common were central
nervous system tumors (25.74%), followed by germ cell tumors (14.52%), primitive
neuroectodermal tumor/Ewing sarcoma (13.86%), Wilms' tumor (8.9%), osteosarcoma
(6.6%), rhabdomyosarcoma (5.6%), colorectal cancer (5.28%), neuroblastoma (4.9%),
and retinoblastoma (2.6%). Outcomes: 33.9% patients went into remission, 35.64%
were defaulters, 2.97% had stable disease, 2.31% had partial response, 20.79%
expired, and 3.96% were still on treatment. Of all these patients, 5.28% had a
relapse. Conclusions: Across the series, advanced stage of presentation, a high
incidence of default and poor follow-up was seen. Multiple interrelated factors
are responsible for the poorer outlook of childhood cancer in Kashmir.
PMID- 29333016
TI - Clinicopathological Features and Outcomes in Primary Central Nervous System
Lymphoma: A 10-year Experience.
AB - Context: Primary central nervous system lymphoma (PCNSL) is a variant of
extranodal lymphoma, accounting for 4% of primary central nervous system tumors.
PCNSL was more common in immunocompetent individuals. International Extranodal
Lymphoma Study Group (IELSG) scoring was used for prognostication. High-dose
methotrexate regimens along with radiotherapy improved outcomes in PCNSL. Aims:
The aim of this study is to analyze the clinical and pathological features,
progression-free survival (PFS), and overall survival (OS) in patients with
PCNSL. Materials and Methods: Data of patients with PCNSL between 2005 and 2016
were retrospectively analyzed. Outcome was analyzed in patients who received
chemotherapy. GraphPad Prism software for Windows Version 6 was used to plot the
Kaplan-Meier curves for PFS and OS. Log-rank test was used to calculate P values.
P < 0.05 was considered as statistically significant. Results: A total of 42
patients were available for analysis. Of these, 34 patients who received
chemotherapy were evaluable for outcome parameters. The median age at
presentation was 46 years (range, 10-75) with male-to-female ratio of 2.2:1. Only
2 (4.7%) patients were HIV positive. Diffuse large B-cell lymphoma (DLBCL) was
the most common histology seen in 41 (97.6%) patients. Using IELSG risk scoring,
scores of 8 (19%), 19 (45.2%), and 15 (35.8%) were stratified into low,
intermediate, and high risk. The median PFS and OS were 11 months (range, 2-72)
and 15.9 months (2.4-80.4), respectively. The median OS was 36.2 months (range,
8.8-72), 15.6 months (2-36), and 6.1 months (2.6-12.7) in low-, intermediate-,
and high-risk groups, respectively, which was statistically significant (P =
0.0002). Conclusions: Immunocompetent patients with PCNSL outnumber
immunocompromised patients. DLBCL was the most common histology, and IELSG risk
stratification significantly predicts the outcome in PCNSL.
PMID- 29333017
TI - Correlation of Hormone Receptor and Human Epidermal Growth Factor Receptor-2/neu
Expression in Breast Cancer with Various Clinicopathologic Factors.
AB - Background: A significant development in the breast carcinoma management is the
correlation between the presence of hormone receptors in the tumor and response
to hormonal therapy and chemotherapy. Human epidermal growth factor receptor
2/neu (Her-2/neu) overexpression also serves as a very useful parameter to
predict response to herceptin. Aim of Study: The study was conducted to correlate
immunohistochemical expression of markers such as estrogen receptor (ER),
progesterone receptor (PR), and Her-2/neu with various clinicopathologic
parameters. Materials and Methods: The study included 509 cases of breast
carcinoma over a period of 5 years (from May 2009 to May 2014).
Immunohistochemistry (IHC) for ER, PR, and her-2/neu was performed. Results: ER
positivity was observed in 42.8% (218/509) cases, PR positivity in 31.8%
(194/509) cases whereas her-2 neu positivity was seen in 40.7% (203/509) cases.
Triple marker (ER, PR, and Her-2/neu) negative cases were 23.6% (120/509) cases.
ER and PR expression was found to have a statistically significant correlation
with tumor grade. Statistically significant correlation was observed between
tumor size and tumor grade and her-2/neu expression. Her-2/neu expression showed
statistically significant association with tumor stage. As the tumor grade
increased, the proportion of triple-negative cases went on increasing, which was
statistically significant. Conclusion: IHC has an increasingly important
prognostic role in determination of factors that affect clinicopathologic
features. Nevertheless, the results of this large series showed different
patterns of findings with respect to clinicopathologic features.
PMID- 29333018
TI - Induction Chemotherapy in Technically Unresectable Locally Advanced T4a Oral
Cavity Squamous Cell Cancers: Experience from a Regional Cancer Center of South
India.
AB - Objectives: The present study aimed to investigate the efficacy, toxicity, and
impact of induction chemotherapy (IC) in technically unresectable T4a oral cavity
squamous cell cancers (OSCCs). Materials and Methods: Patients diagnosed with
technically unresectable locally advanced T4a OSCC from January 2013 and November
2016 at our center, who received 2-3 cycles of IC and then assessed for
resectability, were reviewed retrospectively. Patients' profile, response rates
and toxicity of IC, resectability status, and overall survival (OS) were
evaluated. Statistical analyses were performed using SPSS version 17.0 for
Windows (SPSS Inc., Chicago, IL, USA). Results: Totally 80 patients received IC,
and of them 58 (72.5%) were males. Median age at diagnosis was 44 years (range,
34-62 years). All our patients received IC with doublet regimen. Majority of the
patients had buccal mucosa cancers (73.8%), followed by gingivobuccal complex
(21.2%) and oral tongue (5%) primaries. After IC, partial response was achieved
in 17 (21.3%) patients, stable disease in 49 (61.3%) patients and disease
progression was noted in 14 (17.4%) patients. Post-IC, resectability was achieved
in 19 (23.8%) of 80 patients, but 4 of them did not undergo surgery due to
logistic and personal reasons. The median OS of patients who underwent surgery
followed by adjuvant local therapy (n = 15) was 16.9 months (95% CI: 15.2-19.8
months) and for those treated with nonsurgical local therapy (n = 65) was 8.8
months (95% CI: 6.8-10.6 months) (log-rank P = 0.000). Conclusions: IC had a
manageable toxicity profile and achieved resectability in 23.8% of our patients
with technically unresectable T4a OSCC. Patients underwent resection had a
significantly better median OS than those who received nonsurgical local
treatment.
PMID- 29333020
TI - Oxaliplatin-induced Peripheral Neuropathy in South Indian Cancer Patients: A
Prospective Study in Digestive Tract Cancer Patients.
AB - Purpose: The aim of the current study is to report our prospective experience on
the prevalence of oxaliplatin-induced peripheral neuropathy (OXAIPN) in patients
with digestive tract cancers treated with oxaliplatin-based combination therapy.
Materials and Methods: A total of 219 patients scheduled to be treated with
oxaliplatin-based combination therapy were prospectively examined at baseline and
follow-up during the therapy between November 2014 and December 2016. The
incidence of acute OXAIPN was measured using a descriptive questionnaire (yes/no
question) based on sum of number of symptoms present and NCI-CTCAE version 4.03
was applied to clinically grade the severity of chronic OXAIPN. Results: Acute
and chronic OXAIPN was found in 108 of 219 (49.3%) and 127 of 219 (58%) patients,
respectively. Out of 11 acute OXAIPN symptoms, the vast majority of patients
manifested cold-induced pharyngolaryngeal (63.8%) dysesthesias or perioral
(61.1%) paresthesias. Development of acute OXAIPN was predictive of subsequent
development of chronic OXAIPN (P = 0.0001). All the patients received a median
cumulative dose of 780 mg/m2 (range: 130-1040 mg/m2). There was a significant
correlation between the patients who received the median cumulative dose and the
development of chronic OXAIPN. The incidences of OXAIPN in patients with median
cumulative dose of <=780 mg/m2 was 51/120 (42.5%) and >780 mg/m2 was OXAIPN 76/99
(76.7%) (P = 0.0001). Conclusion: The current study results demonstrate that the
vast majority of patients who receive oxaliplatin-based combination chemotherapy
will manifest acute OXAIPN that may contribute to the development of chronic
peripheral neuropathy on repeated courses of drug administration.
PMID- 29333019
TI - Modulated Radiotherapy with Concurrent and Adjuvant Temozolomide for Anaplastic
Gliomas: Indian Single-center Data.
AB - Objective: To evaluate early clinical outcome for anaplastic gliomas (AG) treated
in the era of modulated radiotherapy (RT) and concurrent plus adjuvant
temozolomide (TMZ) in an Indian setting. Materials and Methods: Fifty-three
patients with AGs treated with modulated RT and concurrent (95%) and adjuvant TMZ
(90%) were analyzed. About 80% of patients had Karnofsky performance status (KPS)
at least 90 with 30% seizure at presentation. Postoperative magnetic resonance
imaging was available in 65% cases and RT dose was 60 Gy in 30 fractions. First
posttreatment imaging was performed at 1 month and then at 3 and 6 months post-RT
and then every 3 months. Kaplan-Meier analysis was used to estimate disease-free
survival (DFS) and overall survival (OS), and analysis was done using SPSS
version 18.0. Results: With median follow-up of 25 months, 2-year DFS and OS were
75% and 88%. There were only 5% symptomatic central nerves system and 8%
symptomatic hematological toxicities. At the 1st evaluation, 30.4% had complete
response (CR), at 3 months 40%, and at 6 months 43%. At 6 months, only 4% had
progressive disease. Forty-six patients were evaluable till the last follow-up
with and 55% had stable to CR. On univariate analysis for DFS, KPS at
presentation >90 (P = 0.001) and response at 6 months (P = 0.02) were significant
and for OS KPS at presentation (P = 0.004) alone. Conclusion: Modulated RT with
TMZ among Grade III glioma patients resulted in minimum treatment-related
toxicities and encouraging survival. Molecular prognostic markers will determine
most favorable groups in future.
PMID- 29333022
TI - 2017 ASCO Highlights on Gastointestinal Malignancies.
PMID- 29333021
TI - Efficacy and Safety of Ibrutinib in Indian Patients with Relapsed or Refractory
Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma: Cases from a Named Patient
Program.
AB - Context: This named patient program evaluated the safety and efficacy of
ibrutinib, a selective inhibitor of Bruton's tyrosine kinase in Indian patients
with relapsed/refractory chronic lymphocytic leukemia (CLL, with/without
chromosome 17 deletion [del17p]) and mantle cell lymphoma (MCL). Subjects and
Methods: The eight enrolled patients (relapsed/refractory CLL: n = 6 [4/6
patients with del17p] and relapsed/refractory MCL: n = 2) had median age of 55
years (range, 52-60) and had received a median of 3 (CLL patients) and 4 (MCL
patients) prior therapies. Patients received once-daily dose of ibrutinib (420
mg: CLL, 560 mg: MCL). Results: In CLL patients, the median time to response was
3 months (range, 0.5-7) and five of six patients had partial response (PR)
whereas one achieved complete response (CR). Median time on treatment was 11.5
months (range, 8-14); five patients continued treatment and one was recommended
stem cell transplantation (SCT). Of the two MCL patients, one achieved PR and one
showed CR and advanced to SCT. In CLL patients, the median (range) hemoglobin
level improved from 9.8 g/dL (7.2-11) at baseline to 12.0 g/dL (9.5-13.2) and
median (range) platelet count improved from 150,000 cells/MUL (21,000-195,000) at
baseline to 190,350 cells/MUL (130,000-394,000) at the time of analysis (July
2016). Most adverse events (AEs) reported were infections (n = 2). No Grade 3-4
or serious AEs, dose reductions, or treatment discontinuation due to AEs were
reported. Conclusions: In this first real-world experience in Indian patients,
ibrutinib demonstrated therapeutic efficacy in relapsed/refractory CLL
(with/without del17p) and MCL. Safety results were consistent with the current
known profile of ibrutinib.
PMID- 29333023
TI - Nivolumab - Pearls of Evidence.
AB - Purpose: Nivolumab is one of the most extensively studied immune checkpoint
inhibitors across various tumor types. In this narrative review, the current
clinical efficacy and safety data of anti-programmed death-1 (PD-1) nivolumab for
nonsmall cell lung cancer (NSCLC) and renal cell cancer (RCC) are elucidated.
Methods: Systematic search was done on Pubmed, Medline, Embase, Web of Knowledge,
and Cochrane Central through September 2016 for controlled prospective
interventional studies of nivolumab across two indications - NSCLC and RCC. There
was heterogeneity at all levels of abstraction; hence, author did not plan to
provide a meta-analysis, but instead, a narrative elaboration of results
structured around the conceptual frameworks. Results: Checkpoint receptor PD-1 is
a negative regulatory molecule expressed by activated T and B lymphocytes.
Binding of PD-1 to its ligands, programmed death-ligands 1 and 2, results in the
downregulation of lymphocyte activation. Nivolumab is a fully human PD-1 immune
checkpoint inhibitor. Nivolumab inhibits the interaction between PD-1 and its
ligands and promotes immune responses including antitumor immune response and
antigen-specific T-cell responses to both foreign antigens as well as self
antigens. In 2013, the Food and Drug Administration granted fast track
designation for nivolumab in NSCLC, RCC, and melanoma. Conclusion: The
encouraging literature on nivolumab lends credibility to the promise of immune
checkpoint blockade, not just in terms of its feasibility as an oncotherapeutic
strategy but also as a key tool of the future in the therapeutic approaches
against advanced cancers.
PMID- 29333024
TI - A Risk-benefit Assessment Approach to Selection of Adjuvant Chemotherapy in
Elderly Patients with Early Breast Cancer: A Mini Review.
AB - Decision-making regarding the use and selection of adjuvant chemotherapy for
breast cancer in elderly patients is challenging due to the presence of age
related comorbidities, frailty, and competing causes of mortality. One area,
relatively neglected in most guidelines, is the effect of competing causes of
mortality on presumed benefit of adjuvant chemotherapy for breast cancer in these
patients. This article utilizes a clinical case to illustrate the principles of
risk-benefit assessment of adjuvant chemotherapy in elderly patients. We suggest
an approach that incorporates validated tools for estimating survival benefits of
adjuvant chemotherapy, geriatric assessment, predicting toxicity, and estimating
remaining life expectancy without cancer. Integration of all these variables
provides a better picture of the possible benefits and harms of adjuvant
chemotherapy in this population compared to conventional approaches that
incorporate tumor-related variables and nonstandard measures of geriatric
assessment.
PMID- 29333025
TI - Primary Leiomyosarcoma of Breast Presenting with Metastasis: An Atypical
Presentation with Dismal Prognosis.
AB - Leiomyosarcoma is an extremely uncommon subtype of breast sarcoma, with <50 cases
reported in the English literature till date. Patients usually present at an
early stage and follow an indolent course. We reported an unusual case of
leiomyosarcoma of breast in a post -menopausal female,presented with right side
breast lump and pain right side hip. Histomorphological evaluation and
immunohistochemistry confirmed the diagnosis. The patient received palliative
radiotherapy 20 Gy in 5 fractions to right iliac bone and was started on
chemotherapy comprising of docetaxel and epirubicin. Leiomyosarcoma of breast is
known to have local recurrence and hematogenous metastasis, usually 10-15 years
after the primary diagnosis. Aggressive behavior of leiomyosarcomas in the form
of such a rapidly growing, fungating mass of 15 cm in greatest dimension with
hematogenous metastasis at the time of initial presentation, as seen in our case,
is extremely unusual.
PMID- 29333027
TI - Ewing's Sarcoma of the Calcaneum.
AB - Ewing's sarcoma of the calcaneum is rare. Radiological features of this tumor can
be misinterpreted as other benign bone tumors due to its rarity. The overall
prognosis of Ewing's sarcoma of calcaneum is inferior compared to other sites of
this tumor. Hence, these tumors should have extensive radiological evaluation and
histological confirmation as misdiagnosis and treatment delays will have
detrimental outcomes.
PMID- 29333026
TI - Renal Lymphoma: Primary or First Manifestation of Aggressive Pediatric B-cell
Lymphoma.
AB - Renal lymphoma is an uncommon renal tumor in children. Unlike renal lymphomas
presenting as bilateral disease and renal failure, we report a boy who presented
with unilateral renal involvement. After initial nephrectomy, he achieved
remission with multiagent chemotherapy but relapsed systemically within 3 months.
He was initiated on salvage chemotherapy with autologous bone marrow transplant.
Even though the initial manifestation was localized lymphoma eventually, it
turned out to be a systemic disease. He succumbed to disease at 14 months from
diagnosis.
PMID- 29333028
TI - Primary Renal Cell Lymphoma: Case Report, Diagnosis, and Management.
AB - The symptoms of primary renal lymphoma (PRL) may mimic a renal cell carcinoma.
Since the diagnosis is mostly after a radical nephrectomy, we recommend a
percutaneous biopsy or cytology from the renal mass in patients who have features
suggestive of a lymphoma. A magnetic resonance imaging may give an image more
specific for a lymphoma. There are no clinical trials for the treatment of PRL,
but all previously published case reports used R-CHOP and a few patients did
better than the median survival of 6 months.
PMID- 29333029
TI - Flagellate Rash: An Unusual Complication of Bleomycin Therapy - A Case Report
with Brief Review of Literature.
AB - Chemotherapy-induced skin rashes are common toxicities encountered which require
careful assessment and evaluation as rashes could be a manifestation of primary
malignancy itself and a variety of drugs used in combination further complicate
the clinical scenario. Bleomycin is an anticancer antibiotic derived from
Streptomyces verticillus and has been commonly used in the treatment of Hodgkin's
disease, germ cell tumors and for pleurodesis. There are various dermatological
adverse effects of bleomycin which have been previously reported in literature
including skin peeling, hyperkeratosis, nail bed changes, Raynaud's phenomenon,
and palmoplantar desquamation. Bleomycin-induced skin rashes are seen
infrequently now a day due to its declining use in clinical practice. We report
here a 29-year-old male with Stage III germ cell tumor who developed widespread
flagellate rash after receiving 3 cycles of bleomycin-based chemotherapy which
responded to treatment with local steroids and omission of bleomycin from further
chemotherapy cycles.
PMID- 29333030
TI - Multiple Myeloma Presenting as Thyroid Plasmacytoma.
AB - Thyroid gland and thyroid cartilage infiltration in multiple myeloma (MM) are
rare. Here, we discuss a patient who presented with hoarseness of voice and was
found to have a hypodense lesion in right lobe of thyroid involving thyroid and
cricoid cartilage. Fine-needle aspiration cytology with immunohistochemistry
revealed extramedullary plasmacytoma of thyroid. MM was ruled out initially by
serum protein electrophoresis, immunofixation, and bone marrow biopsy. Later,
lytic lesions were found in multiple bones on radiation planning scan and he was
finally diagnosed as case of MM with thyroid involvement. Treatment strategies of
MM and thyroid plasmacytoma are also discussed briefly.
PMID- 29333031
TI - A Case of Multifocal Eosinophilic Granuloma Involving Spine and Pelvis in a Young
Adult: A Radiopathological Correlation.
AB - We present a case of multiple osteolytic lesions in a 28-year-old adult who
presented with headache, back pain, and hip pain of 6 months. There was no
history of localized swelling or rise of temperature, no history of weight loss
or evening rise of temperature. On examination, there were no focal neurological
deficits. Routine laboratory investigations, including total leukocyte counts,
differential leukocyte counts, hemoglobin, and platelet counts, were within
normal limits. There was a borderline elevation of erythrocyte sedimentation
rate. Non enhanced computer tomography (NECT) demonstrated no abnormality in the
brain or skull bones. However, incidentally, a lytic lesion involving the third
cervical (C3) vertebral body and the neural arch was detected which also
demonstrated a soft tissue component adjacent to the lytic lesion. These findings
warranted further work up; and magnetic resonance imaging of whole spine and
pelvis was performed that revealed multiple bony lesions involving the cervical
vertebrae, head and neck, bilateral femur, sacrum, and iliac bones. Computed
tomography-guided biopsy was performed from the C3 vertebral lytic lesion which
showed features of eosinophilic granuloma on histopathological evaluation.
PMID- 29333032
TI - Macrodystrophia Lipomatosa: Clinico-patho-radiological Correlation.
AB - Macrodystrophia lipomatosa is a rare congenital nonhereditary developmental
anomaly. It is characterized by hamartomatous proliferation of the soft tissue
leading to disproportionate enlargement of the limbs and digits. Since it leads
to diagnostic dilemma, it has to be differentiated from various other conditions
as they differ in course, prognosis, complications, and treatment. Herein, we
present two cases with localized gigantism and discuss the various differential
diagnoses and need for clinico-patho-radilogical correlation for diagnosis of
this rare entity.
PMID- 29333033
TI - Gastric Teratoma: An Unusual Presentation and Location.
AB - The gastric teratoma is a rare tumor that usually presents as an abdominal mass,
with or without features of gastric outlet obstruction. We report two cases of
gastric teratoma; one - mature in a male neonate and another - ruptured immature
gastric teratoma in a female neonate.
PMID- 29333034
TI - Antinociceptive and Anti-inflammatory Effects of Triterpenes from Pluchea quitoc
DC. Aerial Parts.
AB - Background: Pluchea quitoc DC. (Asteraceae), a medicinal plant known as
"quitoco," "caculucage," "tabacarana" and "madre-cravo," is indicated for
inflammatory conditions such as bronchitis, arthritis, and inflammation in the
uterus and digestive system. Objective: This study evaluated the analgesic and
anti-inflammatory activities of the triterpenes compounds obtained from P. quitoc
aerial parts. Materials and Methods: The triterpenes compounds beta-amyrin,
taraxasterol and pseudo-taraxasterol in a mixture (T); beta-amyrin, taraxasterol
and pseudo-taraxasterol acetates in a mixture (Ta); beta-amyrin, taraxasterol,
pseudo-taraxasterol acetates in a mixture with beta-amyrin, taraxasterol and
pseudo-taraxasterol myristates (Tafe) were analyzed in the models of nociception
and inflammation. The evaluation of antinociceptive activity was carried out by
the acetic acid-induced writhing and tail-flick tests while leukocyte migration
to the peritoneal cavity was used for anti-inflammatory profile. Results: The
oral administration of T or Tafe (40 mg/kg and 70 mg/kg) and Ta (70 mg/kg) to
mice reduced acetic acid-induced writhing. The tail-flick response of mice was
not affected by T or Tafe (40 mg/kg). T or Tafe (40 mg/kg) and Ta (70 mg/kg) also
inhibited peritoneal leukocyte infiltration following the injection of
carrageenan. Conclusion: The results demonstrate the anti-inflammatory and
peripheral antinociceptive activity of the triterpenes beta-amyrin, taraxasterol,
and pseudo-taraxasterol that were decreased when these were acetylated; while the
acetylated triterpenes in mixture with myristyloxy triterpenes improved this
activity. These compounds seem, at least in part, to be related to the plant's
reported activity. SUMMARY: The mixtures of hydroxylated, acetylated, and
myristate triterpenes isolated from hexanic extracts of Pluchea quitoc DC. were
analyzed in the models of nociception and inflammation in mice. The results
demonstrate the anti-inflammatory and peripheral antinociceptive activity of the
triterpenes beta-amyrin, taraxasterol, and pseudo-taraxasterol. This study showed
too that the activity of triterpenes may be decreased by their being acetylated,
while the acetylated triterpenes in mixture with myristate triterpenes improved
this activity.Abbreviations Used: T: Triterpenes compounds beta-amyrin,
taraxasterol, and pseudo-taraxasterol in a mixture, Ta: Triterpenes compounds
beta-amyrin, taraxasterol and pseudo-taraxasterol acetates in a mixture, Tafe:
Triterpenes compounds beta-amyrin, taraxasterol, pseudo-taraxasterol acetates in
a mixture with beta-amyrin, taraxasterol and pseudo-taraxasterol myristates,
Ctrl: Control, Indo: Indomethacin, Dexa: Dexamethasone, EtOAc: Ethyl acetate,
MeOH: Methanol.
PMID- 29333035
TI - The Activity of Immunoglobulin Y Anti-Mycobacterium tuberculosis on Proliferation
and Cytokine Expression of Rat Peripheral Blood Mononuclear Cells.
AB - Objective: It has long been known that chickens, like mammals, are capable of
producing antigen-specific immunoglobulin Y (IgY), which functions similar to
IgG. The present study was performed to investigate the activity of IgY anti
Mycobacterium tuberculosis on proliferation, interleukin (IL)-2, and interferon
(IFN)-gamma expression of rat peripheral blood mononuclear cells (PBMCs).
Materials and Methods: The activity of IgY anti-M. tuberculosis in different
doses (25, 50, and 100 MUg/ml) on rat PBMCs proliferation was determined by 3
(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The production
of IL-2 and IFN-gamma in the PBMC supernatant was determined using enzyme-linked
immunosorbent assay. Investigation was performed on mRNA expression of IL-2 and
IFN-gamma by reverse transcription-polymerase chain reaction (RT-PCR). Results:
IgY anti-M. tuberculosis significantly increased the proliferation of rat PBMC.
Furthermore, IgY anti-M. tuberculosis dose dependently increased IL-2 and IFN
gamma production in PBMC, suggesting that pharmacological activities of IgY anti
M. tuberculosis in PBMC may be mediated by regulating the production of
cytokines. In the RT-PCR, expression of cytokines such as IL-2 and IFN-gamma in
PBMC cultures was increased by IgY anti-M. tuberculosis. Conclusions: We
concluded that increasing IL-2 and IFN-gamma productions in PBMC was related to
IgY anti-M. tuberculosis, stimulating the mRNA transcription (gene expression) of
these cytokines which can induce proliferation of PBMC. SUMMARY: Lohman laying
hens immunized intramuscularly with antigens of M. tuberculosis can produce
specific IgY anti-Mycobacterium tuberculosis complexIgY anti-M. tuberculosis
significantly increased the proliferation of rat peripheral blood mononuclear
cell (PBMC)IgY anti-M. tuberculosis dose dependently increased interleukin 2 (IL
2) and interferon (IFN)-gamma production in PBMCIn the reverse transcription
polymerase chain reaction, expression of cytokines such as IL-2 and IFN-gamma in
PBMC cultures was increased by IgY anti-M. tuberculosisThe increasing IL-2 and
IFN-gamma productions in PBMC were related to stimulation on mRNA transcription
which can induce proliferation of PBMC. Abbreviations Used: IgY anti-M.
tuberculosis: Immunoglobulin Y anti-Mycobacterium tuberculosis; IL-2: Interleukin
2; IFN-gamma: Interferon-gamma; PBMCs: Peripheral blood mononuclear cells.
PMID- 29333036
TI - Autonomic Receptors and Nitric-Oxide Involvements in Mediating Vasorelaxation
Effect Induced by Syzygium polyanthum Leaves Extract.
AB - Context: Syzygium polyanthum (Wight) Walp leaves are traditionally used by Malays
for treating hypertension. Our previous study showed that aqueous extract of S.
polyanthum (AESP) and methanolic extract of S. polyanthum (MESP) extracts of S.
polyanthum leaves significantly reduced blood pressure of normotensive Wistar
Kyoto (WKY) and spontaneously hypertensive rats (SHR). Aims: This study aimed to
investigate their vasorelaxation potential and the possible involvement of
autonomic receptors and nitric oxide in mediating their effect. Settings and
Design: Both extracts will be tested on isolated thoracic aorta rings of WKY and
SHR. The involvement of autonomic receptors and nitric oxide will be elucidated
using respective blockers. Materials and Methods: Isolated thoracic aorta rings
from WKY and SHR were mounted onto myograph chambers to measure changes in the
aorta tension. Increasing concentrations of AESP and MESP, from 1 MUg/ml to 10
mg/ml were added onto the myograph chambers. Blockers such as atropine (1 MUM),
phentolamine (1 MUM), propranolol (1 MUM), and Nomega-nitro-l-arginine methyl
ester (100 MUM) were preincubated before addition of extracts to check for
involvement of muscarinic, alpha- and beta-adrenergic receptors (AR) as well as
nitric oxide, respectively. Statistical Analysis Used: Two-way ANOVA, followed by
post hoc Bonferroni test was used, where P < 0.05 (two-tailed) was considered
statistically significant. Results: AESP and MESP caused significant
vasorelaxations through nitric oxide pathway. The former was mediated through
alpha-AR while the latter was mediated by beta-adrenergic and muscarinic
receptors. Conclusion: Vasorelaxation effect by AESP and MESP involved nitric
oxide pathway which is possibly mediated by the autonomic receptors. SUMMARY:
This is the first study that reveals significant vasorelaxation effect induced by
Syzygium polyanthum leaves extract. Vasorelaxation maybe one of the possible
mechanisms for its ability to reduce blood pressure. This study also suggested
that the vasorelaxation effect by this plant extract may involve nitric oxide
pathway mediated by the autonomic receptors. Abbreviations Used: AESP: Aqueous
extract of Syzygium polyanthum leaves. MESP: Methanolic extract of Syzygium
polyanthum leaves. SHR: spontaneously hypertensive rat, WKY: Wistar-Kyoto rat.
PMID- 29333037
TI - Curcumin and Natural Derivatives Inhibit Ebola Viral Proteins: An In silico
Approach.
AB - Background: Ebola viral disease is a severe and mostly fatal disease in humans
caused by Ebola virus. This virus belongs to family Filoviridae and is a single
stranded negative-sense virus. There is no single treatment for this disease
which puts forth the need to identify new therapy to control and treat this fatal
condition. Curcumin, one of the bioactives of turmeric, has proven antiviral
property. Objective: The current study evaluates the inhibitory activity of
curcumin, bisdemethoxycurcumin, demethoxycurcumin, and tetrahydrocurcumin against
Zaire Ebola viral proteins (VPs). Materials and Methods: Molecular simulation of
the Ebola VPs followed by docking studies with ligands comprising curcumin and
related compounds was performed. Results: The highest binding activity for VP40
is -6.3 kcal/mol, VP35 is -8.3 kcal/mol, VP30 is -8.0 kcal/mol, VP24 is -7.7
kcal/mol, glycoprotein is -7.1 kcal/mol, and nucleoprotein is 6.8 kcal/mol.
Conclusion: Bisdemethoxycurcumin shows better binding affinity than curcumin for
most VPs. Metabolite tetrahydrocurcumin also shows binding affinity comparable to
curcumin. These results indicate that curcumin, curcuminoids, and metabolite
tetrahydrocurcumin can be potential lead compounds for developing a new therapy
for Ebola viral disease. SUMMARY: Curcumin, bisdemethoxycurcumin, and
demethoxycurcumin are active constituents of turmeric. Tetrahydrocurcumin is the
major metabolite of curcumin formed in the body after consumption and absorption
of curcuminoidsCurcuminoids have proven antiviral activityBisdemethoxycurcumin
showed maximum inhibition of Ebola viral proteins (VPs) among the curcuminoids in
the docking procedure with a docking score as high as -8.3
kcal/molTetrahydrocurcumin showed inhibitory activity against Ebola VPs close to
that of curcumin's inhibitory action. Abbreviations Used: EBOV: Ebola virus, GP:
Glycoprotein, NP: Nucleoprotein, NPT: Isothermal-isobaric Ensemble, amount of
substance (N), pressure (P) and temperature (T) conserved, NVE: Canonical
ensemble, amount of substance (N), volume (V) and temperature (T) conserved, VP:
Viral protein.
PMID- 29333038
TI - Antihyperglycemic Potential of Saponin-enriched Fraction from Pithecellobium
dulce Benth. Seed Extract.
AB - Background: Indian traditional system of medicine uses Pithecellobium dulce for
the treatment of diabetes mellitus. Objectives: This study aims to develop an
extract rich in saponins derived from seeds of the plant and to evaluate its
antihyperglycemic potential in vitro and in vivo. Materials and Methods: Defatted
seeds were extracted with methanol and processed to afford saponin-enriched
fraction (Pithecellobium dulce saponin-enriched fraction [PDSEF]). This fraction
was evaluated for its potential to inhibit enzymes such as alpha-glucosidase and
alpha-amylase, in vitro. The fraction was subjected to oral toxicity study
followed by in vivo sucrose tolerance test. An analytical high-performance liquid
chromatography method was developed for fingerprinting of the fraction. Results:
The method adopted for enrichment of saponins was robust enough to enrich saponin
content to 96.37% +/-1.21% w/w. PDSEF displayed superior inhibition of enzymes
(alpha-glucosidase and alpha-amylase with IC50 of 5.12 +/- 0.15 MUg/ml and 17.28
+/- 0.23 MUg/ml, respectively) compared to acarbose. It was found to be safe in
mice up to 2000 mg/kg and significantly prevented blood glucose level in sucrose
tolerance test by inhibiting enzymes responsible for hydrolysis of sucrose.
Conclusion: PDSEF displayed excellent antihyperglycemic activity in vitro and in
vivo and should be evaluated further to develop it as a promising drug for the
management of diabetes mellitus. SUMMARY: Saponin enriched fraction from P. dulce
seeds showed significant inhibition of key enzymes responsible for digestion of
polysaccharides. The saponin enriched fraction was found to be safe in mice and
prevented blood glucose level in mice in sucrose tolerance test. Abbreviations
Used: PDSEF: Pithecellobium dulce saponin-enriched fraction, IC50: Inhibitory
concentration 50, HPLC: High performance liquid chromatography.
PMID- 29333039
TI - Pharmacognostic Assesment of the Endemic and Vulnerable Medicinal Climber
Cayratia pedata (Lam.) Gagnep. var. glabra Gamble and Its Antibacterial Activity.
AB - Objective: The objective of this study is to evaluate a meticulous
pharmacognostic cram is to supplement constructive information with regard to its
identification, characterization, and standardization of endemic and endangered
medicinal climber Cayratia pedata var. glabra and also screening the
antibacterial activity of this climber. Materials and Methods: The morphological
characters of study plant, microscopic examination of leaf powder, anatomy of
young stem, physicochemical analysis of plant powder, extractive values,
phytochemical analysis, powder with different chemical reagents, fluorescence
analysis of plant powder, and other World Health Organization (WHO) recommended
for standardization were analyzed. The antibacterial activity of this study plant
is also analyzed. Results: C. pedata var. glabra belongs to the family Vitaceae,
commonly known as "Kattuppirandai" is one such endemic and endangered species in
Thaisholai, Nilgiris South Division, Western Ghats. With the patronage of veteran
ethnic group traditional knowledge of this region, the species C. pedata var.
glabra was selected for the pharmacognostical examination and antibacterial
screening. There were no pharmacognostical reports of this plant, specifically to
determine the anatomical and other physicochemical standards required for its
quality control. The current study deals with pharmacognostical parameters for
the aerial parts of study plant, which mainly consists of macromorphological and
microanatomical characters, physicochemical constants (ash values and extractive
values), fluorescence analysis, and phytochemical screening, one of the WHO
accepted parameter for the identification of medicinal plants. The
pharmacognostical exploration was undertaken for this species with the purpose of
sketch the pharmacopeial standards. The antibacterial activity of this plant
confirms the therapeutic power. Conclusion: The information obtained from
pharmacognostical studies will be of used for supplementary pharmacological and
therapeutical evaluation of the species and will assist in standardization for
quality, purity, and authentication with the help, of which adulteration and
substitution can be prevented. The antibacterial activity of this plant confirm
the traditional knowledge of local healers on the wound healing property of this
species and also suggest this plant species can be used as a promising source for
the development of new pharmaceuticals that address the therapeutic needs to cure
infectious diseases. SUMMARY: The species C. pedata var. glabra was selected for
present research work, since this species is listed in Red data book and has a
wider use for different ailments among the tribal population of Thiashola due to
its high medicinal value. Pharmacognostical profile was generated from
macroscopical analysis, microscopical studies, powder analysis, physico-chemical
constituent values, fluorescence analysis and preliminary phytochemical
evaluation. The antibacterial activity of this plant confirms the therapeutic
power. Abbreviations Used: WHO: World Health Organization; IUCN: International
Union for the Conservation of Nature.
PMID- 29333040
TI - Pharmacological Screening of Trachyspermum ammi for Antihyperlipidemic Activity
in Triton X-100 Induced Hyperlipidemia Rat Model.
AB - Background: Mortality rate is increasing due to cardiovascular problems
throughout the world. These cardiac problems are directly associated with
dyslipidemia. Aim: The aim of this study was to evaluate the antihyperlipidemic
effect of aqueous extract and methanol extract of Trachyspermum ammi at 1 g/kg, 3
g/kg, and 5 g/kg dose levels in rats. Materials and Methods: For this purpose, 45
male albino rats were used and randomly divided into nine equal groups (n = 5).
The lipid levels were increased after 24 h of single intraperitoneal injection of
Triton X-100 (100 mg/kg) in rats. Aqueous and methanol extracts equivalent to 1
g/kg, 3 g/kg, and 5 g/kg were administered orally to the rats for 21 days.
Atorvastatin (10 mg/kg) was used as standard drug. Blood samples were collected
at 0, 2nd, 9th, 16th, and 23rd day by a direct cardiac puncture in Vacuette(r)
heparin tubes. Serum was separated and then analyzed for lipid profile, liver
function test (LFT), and renal function test (RFT) using standard diagnostic
kits. Results: Results showed that extracts at 3 g/kg and 5 g/kg decreased the
levels of total cholesterol, triglyceride, and low-density lipoprotein and
increased high-density lipoprotein concentration in serum. T. ammi also decreased
LFT and RFT parameters at the end of the study. Conclusion: T. ammi possessed
antioxidant and antihyperlipidemic activities along with hepato- and nephro
protective effects. SUMMARY: Aqueous and methanol extracts of T. ammi were
administered orally at 1-, 3-, and 5 g/kg doses to hyperlipidemic rats (Triton X
100 induced hyperlipidemia) and atorvastatin (10 mg/kg, orally) was used as
standard drug. Methanol extract at 5 g/kg showed antihyperlipidemic effect that
is identical to that of standard drug.Abbreviations Used: LDL: Low-density
lipoprotein; TC: Total cholesterol; VLDL: Very low-density lipoprotein; HDL: High
density lipoprotein; T. ammi: Trachyspermum ammi; WHO: World Health Organization;
CAD: Coronary artery disease; BHT: Butylated hydroxytoluene; BUN: Blood urea
nitrogen; AST: Aspartate transaminase; ALT: Alanine transaminase; IP:
Intraperitoneal.
PMID- 29333041
TI - Pharmacological Evaluation of Hepatoprotective Activity of AHPL/AYTAB/0613 Tablet
in Carbon Tetrachloride-, Ethanol-, and Paracetamol-Induced Hepatotoxicity Models
in Wistar Albino Rats.
AB - Background: Hepatotoxicity ultimately leads to liver failure. Conventional
treatment options for hepatotoxicity are limited and not safe. Objective:
Formulation AHPL/AYTAB/0613 is developed to provide safer and effective
hepatoprotective drug of natural origin. A study was conducted to evaluate
hepatoprotective activity of AHPL/AYTAB/0613 (three dosages) in comparison with
marketed formulations in carbon tetrachloride (CCl4), ethanol, and paracetamol
induced hepatotoxicity in Wistar albino rats. Materials and Methods: Three
separate studies were conducted in models of CCl4, ethanol, and paracetamol
induced hepatotoxicity. Seven groups of animals were studied comparatively to
evaluate the efficacy of AHPL/AYTAB/0613 in low, medium, and high dosage in
comparison with silymarin and a marketed polyherbal formulation. The drugs were
orally administered to rats for 10 days in CCl4 model and for 14 days in ethanol
and paracetamol models. Animals were weighed periodically. After the study
period, blood was tested for serum glutamic-oxaloacetic transaminase (SGOT),
serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP), total
bilirubin, and total protein levels. Liver tissue of sacrificed animals was
examined histopathologically. Results: All the test formulations including all
three dosages of AHPL/AYTAB/0613, significantly reduced levels of SGOT, SGPT,
ALP, total bilirubin, in CCl4, ethanol, and paracetamol-induced hepatotoxicity
models. There was significant increase in total protein level in all the tested
formulations. All the test formulations effectively preserved the structural
integrity of the hepatocellular membrane and liver cell architecture damaged by
CCl4, ethanol, and paracetamol. When compared between groups, no statistically
significant difference was observed. It can be concluded that AHPL/AYTAB/0613
possesses hepatoprotective activity in CCl4, ethanol, and paracetamol-induced
hepatotoxicity in rats. Conclusion: AHPL/AYTAB/0613 can be effectively used as a
hepatoprotective agent in the management of hepatitis caused due to various
toxins. SUMMARY: A polyherbal formulation AHPL/AYTAB/0613 containing Bhringaraja
Eclipta alba extract, Guduchi - Tinospora cordifolia extract, Daruharidra -
Berberis aristata extract, Kakamachi - Solanum nigrum extract, Punarnava -
Boerhaavia diffusa extract, Bhumyamalaki - Phyllanthus niruri extract, Kutaki -
Picrorhiza kurroa extract, and Kalmegha - Andrograhis paniculata extract was
assessed for its hepatoprotective activity. This activity was tested in carbon
tetrachloride (CCl4), ethanol, and paracetamol-induced hepatotoxicity models in
Wistar albino rats in comparison with two marketed formulations. It was observed
that AHPL/AYTAB/0613 significantly reduced levels of serum glutamic-oxaloacetic
transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, total
bilirubin and also significantly increased total protein level. All the test
formulations effectively preserved the structural integrity of the hepatocellular
membrane and liver cell architecture damaged by CCl4, ethanol, and paracetamol.
When compared between groups, no statistically significant difference was
observed. Therefore, it was concluded that AHPL/AYTAB/0613 possesses
hepatoprotective activity in CCl4, ethanol, and paracetamol-induced
hepatotoxicity in rats.Abbreviations Used: CCl4: Carbon tetrachloride, SGOT:
Serum glutamic-oxaloacetic transaminase, SGPT: Serum glutamic pyruvi
transaminase, ALP: Alkaline phosphatase, UDCA: Ursodeoxycholic acid, US: United
States, FDA: Food and Drug Administration, PBC: Primary biliary cirrhosis, GSTA1:
Glutathione S-transferase A1, GSH: Glutathione, GPx: Glutathione peroxidase, GST:
Glutathione S-transferases.
PMID- 29333042
TI - Gas Chromatography Mass Spectrometry Profiling in Methanolic and Ethyl-acetate
Root and Stem Extract of Corbichonia decumbens (Forssk.) Exell from Thar Desert
of Rajasthan, India.
AB - Background: Corbichonia decumbens (Forssk.) Exell (Molluginaceae), recently has
moved to Lophiocarpaceae as per angiospermic plant group (APG) III system, is an
annual or short-lived, dwarf, glabrous subshrub, prefers to grow on rocky places
and on sand-stones in dry, hot areas of Rajasthan. This is the potential plant
with medicinal properties. Vegetative organs under study show antioxidant, anti
inflammatory, antiulcer, antimicrobial, and antinociception activity. Objective:
This study was carried out to identify the phytoconstituents present in the
methanolic and ethyl-acetate extract of root and stem of C. decumbens by GC-MS
analysis. Materials and Methods: Powdered test samples were sequentially
extracted with methanol and ethyl-acetate. The compounds obtained as a result of
GC-MS screening were identified on the basis of their retention time, peak area
and compared with that of literature available and by interpretation of mass
spectra. Results: GC-MS analysis of a methanolic extract of root detected mome
inositol (49.53%), guanosine (20.91%), and cis-vaccenic acid (9.25%). While ethyl
acetate extract of root analyzed pentadecanoic acid (17.91%), octadecanoic acid
(15.01%) and cis-vaccenic acid (12.04%). Methanolic extract of stem detected mome
inositol (75.47%), pentadecanoic acid (6.04%), and 7-tetradecenal, (Z) (4.54%)
while ethyl-acetate extract of stem revealed the presence of 1-heptacosanol
(17.35%), hexadecanoic acid (17.17%), and octadecanal (12.64%). Conclusion: The
results suggest that C. decumbens (Forssk.) Exell is a plant of potential
medicinal value, yielding various bioactive compounds that confirm the
application of this plant as a plant-based drug in pharmacy-industry. SUMMARY:
Extraction is the most important step in the analysis of bioactive compounds
present in botanical preparations. The strength of solvent plays a key role in
this process, methanol as well as ethyl-acetate showed better response as far as
extraction potency is concerned. Gas chromatography mass spectrometry analysis is
highly reliable, and the interpretations of the results are of high-quality. This
tool is in particular useful for confirming of the presence of bioactive
substances. The results suggest that Corbichonia decumbens (Forssk.) Exell can be
used for drug formulations against some major disorders, i.e., cancer, ulcer,
tuberculosis, arthritis, etc.Abbreviations Used: GC-MS: Gas Chromatography-Mass
Spectrometry, kPa: Kilopascal, RT: Retention time, MF: Molecular formula, MW:
Molecular weight.
PMID- 29333044
TI - Antiplasmodial Activity of Isolated Polyphenols from Alectryon serratus Leaves
Against 3D7 Plasmodium falciparum.
AB - Background: Alectryon serratus was selected from a screening program devoted to
search naturally occurring antimalarial compound from plants in Alas Purwo
National Park, Banyuwangi, East Java, Indonesia. The previous studies showed that
ethanol extract of A. serratus leaves contains some polyphenol compounds.
Objective: This study was designed to isolate and investigate antiplasmodial
activity of polyphenol compounds. Material and Methods: The ethanol extract of A.
serratus leaves was fractioned using liquid-liquid fractionation and column
chromatography. Isolated compounds were identified using High-performance liquid
chromatography, ultraviolet-visible, nuclear magnetic resonance, and compared
with references. The isolates were tested in vitro for antiplasmodial activity
against chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Thin blood
smears were used to assess the levels of parasitemia and growth inhibition of the
isolates. Result: Half maximal Inhibitory concentration of Gallic acid (1),
methyl gallate (2), and kempferol-3-O-rhamnoside (3) were 0.0722 MUM, 0.0128 MUM,
and 3.4595 MUM, respectively. Conclusion: The results suggest that gallic acid,
methyl gallate, and kempferol-3-O-rhamnoside isolated from A. serratus leaves
have antiplasmodial activity and are potential to be developed as antimalarial
drugs. SUMMARY: The ethanol extract of Alectryon serratus leaves was successively
fractionated in CH2Cl2, EtOAc, and n-butanol. EtOAc fraction was fractionated
using column chromatography and purified using preparative thin-layer
chromatography (TLC). Isolates were studied for their antiplasmodial activity on
parasites culture of chloroquine-sensitive 3D7 strain of Plasmodium falciparum.
Parasitemia percentages, growth percentages, and inhibition percentages of each
group were calculated. The half maximal inhibitory concentration (IC50) values
that represent the concentration required to inhibit 50% of Plasmodium growth
were calculated from a calibration curve using linear regression. The results
suggest that isolates have antiplasmodial activity and are responsible in the
antimalarial activity of Alectryon serratus leaves. Abbreviations Used: S.F:
Subfraction, EGCG: Epigallocatechingallate, EGC: Epigallocatechin.
PMID- 29333043
TI - Picroside I and Picroside II from Tissue Cultures of Picrorhiza kurroa.
AB - Background: Picrorhiza kurroa (PK) belongs to Scrophulariaceae family and is a
representative endemic, medicinal herb, widely distributed throughout the higher
altitudes of alpine Himalayas from west to east, between 3000 and 4500 m above
mean sea level. Objective: The objective of the present study is to assess the
production of picroside I and picroside II from tissue cultures of PK. Materials
and Methods: Auxiliary shoot tips of PK were incubated in Murashige and Skoog
medium supplemented with indole-3-butyric acid and kinetin phytohormones. The
callus produced was collected at different time intervals and was processed for
extraction of picroside I and picroside II followed by thin layer chromatography
and high-performance liquid chromatography HPLC analysis. Results: The maximum
growth index was found to be 5.109 +/- 0.159 at 16-week-old callus culture. The
estimation of picroside-I and picroside-II was carried out by (HPLC) analysis;
quantity of secondary metabolite found to be 16.37 +/- 0.0007 mg/g for PK-I and
6.34 +/- 0.0012 mg/g for PK-II. Conclusion: This is the first attempt to produce
the Picroside-I and II in large amount by the tissue culture technique. It can be
observed that the method of callus culture can be used in production of secondary
metabolites Picroside-I and II from PK. SUMMARY: Picrorhiza kurroa is a high
value medicinal herb due to rich source of hepatoprotective metabolites,
Picroside-I and Picroside-II. The medicinal importance of P. kurroa is due to its
pharmacological properties like hepatoprotective, antioxidant (particularly in
liver), antiallergic and antiasthamatic, anticancer activity particularly in
liver and immunomodulatory. Shoot apices which were produced a good response was
inoculated on selected medium i.e., on MS medium containing 2, 4 D (mg/l) + KN
(1mg/l) for induction of callus. The initiation of callus was observed after
4weeks and it was light green and fragile Maximum growth was observed with 3% w/v
of sucrose supplement. The callus culture was maintained and growth index was
recorded after every subculture. The growth index was calculated from the
obtained final dried weight divided by initial weight.Abbreviations Used: PK
Picrorhizakurroa, IBA-Indole-3-butyricacid, KN-Kinetin, 2,4D-2,4Dichlorophenoxy
acetic acid.
PMID- 29333045
TI - In vitro Antiproliferative Effect of Earthworm Coelomic Fluid of Eudrilus
Eugeniae, Eisenia Foetida, and Perionyx Excavatus on Squamous Cell Carcinoma-9
Cell Line: A Pilot Study.
AB - Introduction: The earthworm coelomic fluid (ECF) has shown proven
antiproliferative effect against breast, liver, gastrointestinal, and brain
cancer, but it is least explored in oral cancer. The present in vitro study is an
attempt to investigate the antiproliferative activity of ECF on oral cancer cell
line squamous cell carcinoma (SCC)-9. Materials and Methods: ECF was collected
from the species Eudrilus eugeniae (EE), Eisenia foetida (EF), and Perionyx
excavatus (PE) stored at -80 degrees C. Percentage inhibition of ECF on squamous
cell carcinoma-9 cells in vitro was recorded at 24 h. Protein estimation was done
using Bradford protein assay validated by the biuret method. Cytotoxicity was
tested at 2.5, 5, 10, 20, 40, and 80 MUg/ml concentrations by 3-(4,5
dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay in SCC-9 cells in
vitro. GraphPad Prism 7.0 software was used to calculate the inhibitory
concentration (IC50). Chi-square test was used to analyze the difference between
samples. Results: The test samples EE, EF, and PE inhibited the growth of SCC-9
cells significantly in a dose-dependent manner, and the IC50 values were found to
be 4.6, 44.69, and 5.27 MUg/ml, respectively. The antiproliferative effect was
found to be variable among the three earthworm species with EE showing the most
promising effect followed by PE and EF. Conclusion: Establishing the
antiproliferative effect of ECF on oral cancer cells could be an initial step
toward drug development and future anticancer research. The preliminary
investigation has shown that ECF has a promising antiproliferative effect on oral
cancer cells in vitro. SUMMARY: The present pilot study evaluated the in vitro
antiproliferative effect of earthworm coelomic fluid (ECF) of Eudrilus eugeniae
(EE), Eisenia foetida (EF), and Perionyx excavatus (PE) on squamous cell
carcinoma-9 cell line. The ECF inhibitory activity was promising at inhibitory
concentration values of 4.6, 44.69, and 5.27 MUg/ml, respectively. Further
studies pertaining to antiproliferative mechanism of EE, EF, and PE have been
planned.Abbreviations Used: ECF: Earthworm coelomic fluid, EE: Eudrilus eugeniae,
EF: Eisenia foetida, PE: Perionyx excavatus, MTT: 3-(4,5-dimethylthiazol-2-yl)
2,5-diphenyltetrazolium bromide, SCC: Squamous cell carcinoma, BSA: Bovine serum
albumin, PBS: Phosphored buffered saline, ATCC: American Type Culture Collection.
PMID- 29333046
TI - Development and validation of High-performance Thin-layer Chromatography Method
for Simultaneous Determination of Polyphenolic Compounds in Medicinal Plants.
AB - Context: Quantitative standardization of plant-based products is challenging
albeit essential to maintain their quality. Aims: This study aims to develop and
validate high-performance thin-layer chromatography (HPTLC) method for the
simultaneous determination of rutin (Ru), quercetin (Qu), and gallic acid (Ga)
from Psidium guajava Linn. (PG) and Aegle marmelos (L.) Correa. (AM) and
correlate with antioxidant activity. Materials and Methods: The stock solution (1
mg/mL) of standard Ru, Qu, and Ga in methanol: Water (1:1) was serially diluted
and spotted (5 MUL) on slica gel 60 F254 thin-layer chromatography plates.
Toluene: Ethyl acetate: Formic acid: Methanol (3:4:0.8:0.7, v/v/v) was selected
as mobile phase for analysis at 254 nm. Hydroalcoholic (1:1) extracts of leaves
of PG and AM were fractionated and similarly analyzed. Antioxidant activity was
also determined using 2, 2-diphenyl-1-picrylhydrazyl assay. Results: The
developed method was robust and resolved Ru, Qu, and Ga at Rf 0.08 +/- 0.02, 0.76
+/- 0.01, and 0.63 +/- 0.02, respectively. The intra-day, interday precision, and
interanalyst were <2% relative standard deviation. The limit of detection and
limit of quantification for Ru, Qu, and Ga were 4.51, 4.2, 5.27, and 13.67,
12.73, 15.98 ng/spot, respectively. Antioxidant activity (Log 50% inhibition) of
PG and AM was 4.947 +/- 0.322 and 6.498 +/- 0.295, respectively. Conclusion: The
developed HPTLC method was rapid, accurate, precise, reproducible, and specific
for the simultaneous estimation of Ru, Qu, and Ga. SUMMARY: HPTLC method for
simultaneous determination and quantification of Rutin, Quercetin and Gallic
acid, is reported for quality control of herbal drugs.Abbreviations Used: A:
Aqueous fraction; AM: Aegle marmelos L. Correa; B: Butanol fraction; C:
Chloroform fraction; EA: Ethyl acetate fraction; Ga: Gallic acid; H: Hexane
fraction; HA: Hydroalcoholic extract; HPTLC: High-performance thin-layer
chromatography; PG: Psidium guajava; Qu: Quercetin; Ru: Rutin.
PMID- 29333047
TI - Assessment of Nutritional Quality and Global Antioxidant Response of Banana (Musa
sp. CV. Nanjangud Rasa Bale) Pseudostem and Flower.
AB - Background: The assessment of the nutritional composition and phytochemical
screening of banana pseudostem (PB) and flower (FB) advocate this nonconventional
food source for routine consumption, considering its various health benefits.
Objectives: The aim is to assess the proximate nutrient composition, fatty acids,
minerals, amino acid profile, and global antioxidant response (GAR) of PB and FB.
Methods: Standard analytical procedures were used to determine the nutritional
quality and GAR of PB and FB. Results: The chemical analysis illustrated that
functional profile (water holding capacity, oil holding capacity, swelling power,
and solubility), and proximate (ash, moisture, protein, fat, dietary fiber, and
carbohydrate) contents were substantially high in FB than PB. With a well
proportionate amino acid profile, PB (0.56) and FB (0.54) comprised of a high
ratio of essential to nonessential amino acids than those of FAO/WHO requirement
(0.38). The mineral analysis revealed that PB and FB were rich in macro and micro
minerals in the order K > Ca > Mg > P > Na and K > Mg > Na > Ca > P,
respectively. Linoleic acid was found to be the major component in PB and FB.
Besides, total antioxidant activity conducted for PB and FB by GAR method,
measuring both bio-accessible and insoluble fractions, revealed that the soluble
fraction fared better than the chemical extracts. Conclusion: The results
revealed high nutritional qualities of the byproducts of banana and the low cost
of its production promotes their use as a prospective nonconventional food
resource with high nutraceutical value. SUMMARY: AOAC: Association of Analytical
CommunitiesFAO/WHO: Food and Agriculture Organization of the United Nations/World
health organization Abbreviations Used: Banana flower was more potent than banana
pseudostem in terms of its nutritional quality and total antioxidant capacity
affirming their usefulness (of both the secondary products) in the pharmaceutical
sector as a nutritional supplement due to the health-related properties of
dietary fibre and associated bioactive compounds.
PMID- 29333048
TI - Astaxanthin Ameliorates Hepatic Damage and Oxidative Stress in Carbon
Tetrachloride-administered Rats.
AB - Background: Astaxanthin is of carotenoids group which possess strong antioxidant
properties. The present study was conducted to evaluate the hepatoprotective
effects of astaxanthin in carbon tetrachloride (CCl4)-treated rats. Materials and
Methods: Female Long-Evans rats were administered with CCl4 orally (1 ml/kg)
twice a week for 2 weeks and were treated with astaxanthin (10 mg/kg) every day
for 2 weeks. Blood plasma samples were isolated from each group and were analyzed
for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and
alkaline phosphatase activities. Oxidative stress parameters such as
malondialdehyde (MDA), nitric oxide (NO), and advanced protein oxidation product
(APOP) were measured. Several enzyme functions such as myeloperoxidase (MPO),
superoxide dismutase (SOD), and catalase (CAT) activities in the plasma and liver
tissues were also analyzed. Moreover, inflammation and tissue fibrosis were also
confirmed by histological staining of liver tissues. Results: This investigation
revealed that CCl4 administration in rats increased plasma AST, ALT, and ALP
activities which were normalized by astaxanthin treatment. Moreover, CCl4
administration increased as MDA, NO, and APOP level both in plasma and tissues
compared to control rats. Astaxanthin also exhibited a significant reduction of
those parameters in CCl4-administered rats. Astaxanthin treatment also restored
the CAT and SOD activities and lowered MPO activity in CCl4-administered rats.
Histological assessment also revealed that the astaxanthin prevented the
inflammatory cells infiltration, decreased free iron deposition, and fibrosis in
liver of CCl4-administered rats. Conclusion: These results suggest that
astaxanthin protects liver damage induced by CCl4 by inhibiting lipid
peroxidation and stimulating the cellular antioxidant system. SUMMARY: Carbon
tetrachloride (CCl4) administration increased oxidative stress-mediated hepatic
damage and inflammation in ratsAstaxanthin, a potent antioxidant, prevents
oxidative stress and inflammatory cells infiltration in CCl4-administered
ratsAstaxanthin also ameliorated the progression of hepatic fibrosis in CCl4
administered rats. Abbreviations Used: APOP: Advanced protein oxidation product;
AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline
phosphatase; CAT: Catalase; CCl4: Carbon tetrachloride; CVD: Cardiovascular
disease; HSCs: Hepatic stellate cells; H2O2: Hydrogen peroxide; MDA:
Malondialdehyde; MMP2: Matrix metalloproteinase2; MPO: Myeloperoxidase; NF
kappaB: Nuclear factor kappa B; NO: Nitric oxide; Nrf2: Nuclear factor erythroid
2-related factor 2; .ONOO-: Peroxynitrate; ROS: Reactive oxygen species; SOD:
superoxide dismutase; TCA: Trichloroacetic acid; TBA: Thiobarbituric acid; TGF-1:
Transforming growth factor 1, TGF-beta: Transforming growth factor-beta; TIMP1:
Tissue inhibitor of metalloproteinase 1; TNF-alpha: Tumor necrosis factor
alpha;.CCl3: Trichloromethyl free radical; CCl3O2-: Trichloroperoxyl radical.
PMID- 29333050
TI - Improvement of Insulin Secretion and Pancreatic beta-cell Function in
Streptozotocin-induced Diabetic Rats Treated with Aloe vera Extract.
AB - Background: Diabetes mellitus is a metabolic disorder characterized by chronic
hyperglycemia. Plant extracts and their products are being used as an alternative
system of medicine for the treatment of diabetes. Aloe vera has been
traditionally used to treat several diseases and it exhibits antioxidant, anti
inflammatory, and wound-healing effects. Streptozotocin (STZ)-induced Wistar
diabetic rats were used in this study to understand the potential protective
effect of A. vera extract on the pancreatic islets. Objective: The aim of the
present study was to evaluate the A. vera extract on improvement of insulin
secretion and pancreatic beta-cell function by morphometric analysis of
pancreatic islets in STZ-induced diabetic Wistar rats. Materials and Methods:
After acclimatization, male Wistar rats, maintained as per the Committee for the
Purpose of Control and Supervision of Experiments on Animals guidelines, were
randomly divided into four groups of six rats each. Fasting plasma glucose and
insulin levels were assessed. The effect of A. vera extract in STZ-induced
diabetic rats on the pancreatic islets by morphometric analysis was evaluated.
Results: Oral administration of A. vera extract (300 mg/kg) daily to diabetic
rats for 3 weeks showed restoration of blood glucose levels to normal levels with
a concomitant increase in insulin levels upon feeding with A. vera extract in STZ
induced diabetic rats. Morphometric analysis of pancreatic sections revealed
quantitative and qualitative gain in terms of number, diameter, volume, and area
of the pancreatic islets of diabetic rats treated with A. vera extract when
compared to the untreated diabetic rats. Conclusion: A. vera extract exerts
antidiabetic effects by improving insulin secretion and pancreatic beta-cell
function by restoring pancreatic islet mass in STZ-induced diabetic Wistar rats.
SUMMARY: Fasting plasma glucose (FPG) and insulin levels were restored to normal
levels in diabetic rats treated with Aloe vera extractIslets of pancreas were
qualitatively and quantitatively restored to normalcy leading to restoration of
FPG and insulin levels of diabetic rats treated with Aloe vera
extractMorphometric analysis of pancreatic sections revealed quantitative and
qualitative gain in terms of number, diameter, volume, and area of the pancreatic
islets of diabetic rats treated with Aloe vera extract when compared to the
untreated diabetic rats. Abbreviations Used:A. vera, FPG: Fasting plasma glucose,
STZ: Streptozotocin, BW: Body weight.
PMID- 29333049
TI - Marine-derived Fungi Extracts Enhance the Cytotoxic Activity of Doxorubicin in
Nonsmall Cell Lung Cancer Cells A459.
AB - Background: Drug resistance is a major concern in the current chemotherapeutic
approaches and the combination with natural compounds may enhance the cytotoxic
effects of the anticancer drugs. Therefore, this study evaluated the cytotoxicity
of crude ethyl extracts of six marine-derived fungi - Neosartorya tsunodae KUFC
9213 (E1), Neosartorya laciniosa KUFC 7896 (E2), Neosartorya fischeri KUFC 6344
(E3), Aspergillus similanensis KUFA 0013 (E4), Neosartorya paulistensis KUFC 7894
(E5), and Talaromyces trachyspermum KUFC 0021 (E6) - when combined with
doxorubicin (Dox), in seven human cancer cell lines. Materials and Methods: The
antiproliferative activity was primarily assessed by the 3-(4,5-dimethylthiazol-2
yl)-2,5-diphenyltetrazolium bromide assay. Results: Two extracts, E1 and E2,
demonstrated a significant enhancement of Dox's cytotoxicity in nonsmall cell
lung cancer A549 cells. Accumulation of Dox in the nuclei increased when A549
cells were treated in combination with extracts E1 and E2, with induction of cell
death observed by the nuclear condensation assay. The combination of E2 with Dox
increased the DNA damage as detected by the comet assay. Ultrastructural
observations by transmission electron microscopy suggest an autophagic cell death
due to an increase of autophagic vesicles, namely with the combination of Dox
with E1 and E2. Conclusion: These findings led to the conclusion that the fungal
extracts E1 and E2 potentiate the anticancer action of Dox, through nuclear
accumulation of Dox with induction of cell death mainly by cytotoxic autophagy.
SUMMARY: Fungal extracts increase the cytotoxic activity of doxorubicin (Dox) in
lung cancer cellsNuclear accumulation of Dox, DNA damage, and cell death as a
mechanism of actionFungal extracts may potentiate the anticancer activity of
conventional drugs.Abbreviations Used: A375: Human malignant melanoma cell line,
A549: Human non small lung cancer cell line, DAPI: 4,6-Diamidino-2-phenylindole,
DMEM: Dulbecco's Modified Eagle Medium, DMSO: Dimethylsulfoxide, Dox:
Doxorubicin, DSBs: DNA double-strand breaks, E1: Neosartorya tsunodae KUFC 9213,
E2: Neosartorya laciniosa KUFC 7896, E3: Neosartorya fischeri KUFC 6344, E4:
Aspergillus similanensis KUFA 0013, E5: Neosartorya paulistensis KUFC 7894, E6:
Talaromyces trachyspermum KUFC 0021, FBS: Fetal bovine serum, HCT116: Human
colorectal carcinoma cell line, HEPES: (N-[2-hydroxyethyl] piperazine-N'- [2
ethane-sulfonic acid]), HepG2: Human hepatocellular carcinoma cell line, HT29:
Human Caucasian colon adenocarcinoma Grade II cell line, IC50: Concentration of
the extract or Dox that inhibits cell viability by 50%, LRP: Lung resistance
related protein, MCF7: Human breast adenocarcinoma cell line, MEM: Minimum
Essential Medium Eagle, MRPs: Multidrug resistance-associated proteins, MTT: 3
(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, PBS: Phosphate
buffered saline, NSCLC: Nonsmall cell lung cancer, P-gp: P-glycoprotein, ROS:
Reactive oxygen species, RPMI: Roswell Park Memorial Institute Medium, TEM:
Transmission electron microscopy, U251: Human glioblastoma astrocytoma cell line.
PMID- 29333051
TI - Therapeutic Significance of Loligo vulgaris (Lamarck, 1798) ink Extract: A
Biomedical Approach.
AB - Background: The squid ink extract is well known for its biomedical properties.
Objective: In this study, squid Loligo vulgaris was collected from Tuticorin
costal water, Bay of Bengal, India. Materials and Methods: Proximate composition
of the crude squid ink was studied and found to have protein as the major
component over lipid and carbohydrates. Further, bioactive fractions of squid ink
were extracted with ethanol, and therapeutic applications such as hemolytic,
antioxidant, antimicrobial, and in vitro anti-inflammatory properties were
analyzed using standard methods. Results: In hemolytic assay, the squid ink
extract exhibited a maximum hemolytic activity of 128 hemolytic unit against
tested erythrocytes. In DPPH assay, the ethanolic extract of squid ink has
exhibited an antioxidant activity of 83.5%. The squid ink was found to be potent
antibacterial agent against the pathogens tested. 200 MUL of L. vulgaris ink
extract showed remarkable antibacterial activity as zone of inhibition against
Escherichia coli (28 mm), Klebsiella pneumoniae (22 mm), Pseudomonas aeruginosa
(21 mm), and Staphylococcus aureus (24 mm). The 68.9% inhibition of protein
denaturation by the squid ink extract indicated that it has very good in vitro
anti-inflammatory properties. The Fourier transform infrared spectroscopy
analysis of the ethanolic extracts of the squid ink indicated the presence of
functional groups such as 1 degrees and 2 degrees amines, amides, alkynes
(terminal), alkenes, aldehydes, nitriles, alkanes, aliphatic amines, carboxylic
acids, and alkyl halides, which complements the biochemical background of
therapeutic applications. Conclusion: Hence, results of this study concluded that
the ethanolic extract of L. vulgaris has many therapeutic applications such as
antimicrobial, antioxidant, and anti-inflammatory activities. SUMMARY: Squid ink
is very high in a number of important nutrients. It's particularly high in
antioxidants for instance, which as well all know help to protect the cells and
the heart against damage from free radicals. In the present study, the squid ink
have antioxidant, anti-inflammatory and cytotoxic properties and can be
considered as promising the developing the drugs. Abbreviations Used: DPPH: 2,2
diphenyl-1-picrylhydrazyl, FTIR: Fourier-transform infrared spectroscopy, BSA:
Bovine Serum Albumin.
PMID- 29333052
TI - A calcium rise occurs as activating Drosophila eggs move through the female
reproductive tract.
PMID- 29333053
TI - An Emic, Mixed Methods Approach to Defining and Measuring Positive Parenting
Among Low-Income, Black Families.
AB - Research Findings: This within-group exploratory sequential mixed methods
investigation sought to identify how ethnically diverse, urban-residing, low
income Black families conceptualize positive parenting. During the item
development phase 119 primary caregivers from Head Start programs participated in
focus groups and interviews. These qualitative data were content analyzed using a
three-stage iterative process that resulted in the development of a final set of
72 items for a paper-and-pencil measure. In the measure validation phase of the
study initial construct validity of the 72-item measure was assessed with an
independent sample of 665 respondents. Common factor analyses revealed five
dimensions of positive parenting on the Black Parenting Strengths in Context
(BPSC) scale that related in expected ways with other parent self-report
measures. Practice and Policy: BPSC dimensions provide initial support for a more
nuanced operationalization of positive parenting than currently exists in any
single scale for use with this group, and hold promise for better honoring the
culture- and context-specific parenting goals and practices that low-income,
Black parents subjectively view as important for producing healthy developmental
outcomes for their children.
PMID- 29333054
TI - On Fitting a Multivariate Two-Part Latent Growth Model.
AB - A 2-part latent growth model can be used to analyze semicontinuous data to
simultaneously study change in the probability that an individual engages in a
behavior, and if engaged, change in the behavior. This article uses a Monte Carlo
(MC) integration algorithm to study the interrelationships between the growth
factors of 2 variables measured longitudinally where each variable can follow a 2
part latent growth model. A SAS macro implementing Mplus is developed to estimate
the model to take into account the sampling uncertainty of this simulation-based
computational approach. A sample of time-use data is used to show how maximum
likelihood estimates can be obtained using a rectangular numerical integration
method and an MC integration method.
PMID- 29333055
TI - Corporal Punishment in U.S. Public Schools: Prevalence, Disparities in Use, and
Status in State and Federal Policy.
AB - School corporal punishment is currently legal in 19 states, and over 160,000
children in these states are subject to corporal punishment in schools each year.
Given that the use of school corporal punishment is heavily concentrated in
Southern states, and that the federal government has not included corporal
punishment in its recent initiatives about improving school discipline, public
knowledge of this issue is limited. The aim of this policy report is to fill the
gap in knowledge about school corporal punishment by describing the prevalence
and geographic dispersion of corporal punishment in U.S. public schools and by
assessing the extent to which schools disproportionately apply corporal
punishment to children who are Black, to boys, and to children with disabilities.
This policy report is the first-ever effort to describe the prevalence of and
disparities in the use of school corporal punishment at the school and school
district levels. We end the report by summarizing sources of concern about school
corporal punishment, reviewing state policies related to school corporal
punishment, and discussing the future of school corporal punishment in state and
federal policy.
PMID- 29333056
TI - Individual Differences in Phonological Feedback Effects: Evidence for the
Orthographic Recoding Hypothesis of Orthographic Learning.
AB - Share (1995) has proposed phonological recoding (the translation of letters into
sounds) as a self-teaching mechanism through which readers establish complete
lexical representations. More recently, McKague et al. (2008) proposed a similar
role for orthographic recoding, i.e., feedback from sounds to letters, in
building and refining lexical representations. We reasoned that an interaction
between feedback consistency measures and spelling ability in a spelling decision
experiment would lend support to this hypothesis. In a linear mixed effects
logistic regression of accuracy data this interaction was significant. Better
spellers but not poorer spellers were immune to feedback effects in deciding if a
word is spelled correctly, which is consistent with McKague et al.'s prediction
that the impact of phonological feedback on word recognition will diminish when
the orthographic representation for an item is fully specified. The study
demonstrates the importance of considering individual differences when
investigating the role of phonology in reading.
PMID- 29333057
TI - Family counts: deciding when to murder among the Icelandic Vikings.
AB - In small scale societies, lethal attacks on another individual usually invite
revenge by the victim's family. We might expect those who perpetrate such attacks
to do so only when their own support network (mainly family) is larger than that
of the potential victim so as to minimise the risk of retaliation. Using data
from Icelandic family sagas, we show that this prediction holds whether we
consider biological kin or affinal kin (in-laws): on average, killers had twice
as many relatives as their victims. These findings reinforce the importance of
kin as a source of implicit protection even when they are not physically present.
The results also support Hughes' (1988) claim that affines are biological kin
because of the shared genetic interests they have in the offspring generation.
PMID- 29333058
TI - Acquisition of a socially learned tool use sequence in chimpanzees: Implications
for cumulative culture.
AB - Cumulative culture underpins humanity's enormous success as a species. Claims
that other animals are incapable of cultural ratcheting are prevalent, but are
founded on just a handful of empirical studies. Whether cumulative culture is
unique to humans thus remains a controversial and understudied question that has
far-reaching implications for our understanding of the evolution of this
phenomenon. We investigated whether one of human's two closest living primate
relatives, chimpanzees, are capable of a degree of cultural ratcheting by
exposing captive populations to a novel juice extraction task. We found that
groups (N = 3) seeded with a model trained to perform a tool modification that
built upon simpler, unmodified tool use developed the seeded tool method that
allowed greater juice returns than achieved by groups not exposed to a trained
model (non-seeded controls; N = 3). One non-seeded group also discovered the
behavioral sequence, either by coupling asocial and social learning or by
repeated invention. This behavioral sequence was found to be beyond what an
additional control sample of chimpanzees (N = 1 group) could discover for
themselves without a competent model and lacking experience with simpler,
unmodified tool behaviors. Five chimpanzees tested individually with no social
information, but with experience of simple unmodified tool use, invented part,
but not all, of the behavioral sequence. Our findings indicate that (i) social
learning facilitated the propagation of the model-demonstrated tool modification
technique, (ii) experience with simple tool behaviors may facilitate individual
discovery of more complex tool manipulations, and (iii) a subset of individuals
were capable of learning relatively complex behaviors either by learning
asocially and socially or by repeated invention over time. That chimpanzees learn
increasingly complex behaviors through social and asocial learning suggests that
humans' extraordinary ability to do so was built on such prior foundations.
PMID- 29333060
TI - Optimising human community sizes.
AB - We examine community longevity as a function of group size in three historical,
small scale agricultural samples. Community sizes of 50, 150 and 500 are
disproportionately more common than other sizes; they also have greater
longevity. These values mirror the natural layerings in hunter-gatherer societies
and contemporary personal networks. In addition, a religious ideology seems to
play an important role in allowing larger communities to maintain greater
cohesion for longer than a strictly secular ideology does. The differences in
optimal community size may reflect the demands of different ecologies, economies
and social contexts, but, as yet, we have no explanation as to why these numbers
seem to function socially so much more effectively than other values.
PMID- 29333059
TI - Innate food aversions and culturally transmitted food taboos in pregnant women in
rural southwest India: separate systems to protect the fetus?
AB - Pregnancy increases women's nutritional requirements, yet causes aversions to
nutritious foods. Most societies further restrict pregnant women's diet with food
taboos. Pregnancy food aversions are theorized to protect mothers and fetuses
from teratogens and pathogens or increase dietary diversity in response to
resource scarcity. Tests of these hypotheses have had mixed results, perhaps
because many studies are in Westernized populations with reliable access to food
and low exposure to pathogens. If pregnancy food aversions are adaptations,
however, then they likely evolved in environments with uncertain access to food
and high exposure to pathogens. Pregnancy food taboos, on the other hand, have
been theorized to limit resource consumption, mark social identity, or also
protect mothers and fetuses from dangerous foods. There have been few tests of
evolutionary theories of culturally transmitted food taboos. We investigated
these and other theories of psychophysiological food aversions and culturally
transmitted food taboos among two non-Western populations of pregnant women in
Mysore, India, that vary in food insecurity and exposure to infectious disease.
The first was a mixed caste rural farming population (N = 72), and the second was
the Jenu Kurubas, a resettled population of former hunter-gatherers (N = 30).
Women rated their aversions to photos of 31 foods and completed structured
interviews that assessed aversions and socially learned avoidances of foods,
pathogen exposure, food insecurity, sources of culturally acquired dietary
advice, and basic sociodemographic information. Aversions to spicy foods were
associated with early trimester and nausea and vomiting, supporting a protective
role against plant teratogens. Variation in exposure to pathogens did not explain
variation in meat aversions or avoidances, however, raising some doubts about the
importance of pathogen avoidance. Aversions to staple foods were common, but were
not associated with resource stress, providing mixed support for the role of
dietary diversification. Avoided foods outnumbered aversive foods, were believed
to be abortifacients or otherwise harmful to the fetus, influenced diet
throughout pregnancy, and were largely distinct from aversive foods. These
results suggest that aversions target foods with cues of toxicity early in
pregnancy, and taboos target suspected abortifacients throughout pregnancy.
PMID- 29333061
TI - Critical appraisal of Rome IV criteria: hypersensitive esophagus does belong to
gastroesophageal reflux disease spectrum.
AB - The Rome IV Committee introduced a major change in the classification of
functional gastrointestinal disorders, proposing a more restrictive definition of
gastroesophageal reflux disease (GERD). It was suggested that hypersensitive
esophagus (HE) may sit more firmly within the functional realm. It was suggested
that GERD diagnosis should be based upon abnormal acid exposure time (AET) only,
implying no advantage of impedance-pH over pH monitoring. Symptom association
probability (SAP), symptom index (SI) and heartburn relief with proton pump
inhibitor (PPI) therapy were regarded as unreliable, whereas a lack of response
to PPI was considered as evidence of functional heartburn. These assumptions are
contradicted by numerous studies showing the clinical relevance of weakly acidic
refluxes and the diagnostic utility of SAP, SI and new impedance parameters,
namely the post-reflux swallow-induced peristaltic wave (PSPW) index and the mean
nocturnal baseline impedance (MNBI). The PSPW index and MNBI provide significant
diagnostic advantage, particularly in patients with normal AET who can be
classified as HE when both parameters are abnormal, even though SAP and SI are
negative. Visceral pain modulators are recommended by the Rome IV Committee
despite scanty evidence of efficacy, but a positive outcome with medical or
surgical anti-reflux treatment has been reported by several studies of HE
patients. Therefore, we believe that patients with endoscopy-negative heartburn
should be investigated by means of impedance-pH monitoring with analysis of PSPW
index and MNBI: such an approach provides accurate identification of HE cases,
who remain, in our opinion, within the realm of GERD and should be treated
accordingly.
PMID- 29333062
TI - Helicobacter pylori infection and esophageal adenocarcinoma: a review and a
personal view.
AB - Esophageal adenocarcinoma (EAC) is etiologically associated with gastroesophageal
reflux disease (GERD). There is evidence to support the sequence GERD, Barrett's
esophagus (BE), dysplasia, and finally EAC, with Helicobacter pylori (H. pylori)
being implicated in each step to EAC. On the other side of this relation stands
the hypothesis of the protective role of H. pylori against EAC. Based on this
controversy, our aim was to review the literature, specifically original clinical
studies and meta-analyses linking H. pylori infection with EAC, but also to
provide our personal and others' relative views on this topic. From a total of
827 articles retrieved, 10 original clinical studies and 6 meta-analyses met the
inclusion criteria. Original studies provided inconclusive data on an inverse or
a neutral association between H. pylori infection and EAC, whereas meta-analyses
of observational studies favor an inverse association. Despite these data, we
consider that the positive association between H. pylori infection and GERD or
BE, but not EAC, is seemingly a paradox. Likewise, the oncogenic effect of H.
pylori infection on gastric and colon cancer, but not on EAC, also seems to be a
paradox. In this regard, well-designed prospective cohort studies with a powered
sample size are required, in which potential confounders should be taken into
consideration since their design.
PMID- 29333063
TI - Familial and ethnic risk in inflammatory bowel disease.
AB - Familial aggregation in inflammatory bowel disease (IBD) has been established for
several decades, reflecting shared genetic and environmental susceptibility. A
positive family history remains the strongest recognizable risk factor for the
development of IBD and is reported in around 8-12% of IBD patients. Crohn's
disease shows a more frequent familial pattern than ulcerative colitis. The risk
of developing IBD in first-degree relatives of an affected proband is increased 4
to 8-fold. The risk for twins and children born from couples who both have IBD
is also substantially higher; a cumulative effect of the number of family members
affected has been described, with the highest incidence being described for
families with three or more affected members. Herein, we review the available
evidence regarding familial IBD, and briefly discuss the variation of IBD across
different races and ethnicities, hoping to provide a useful update and a
practical guide that can serve clinicians as a guide for counseling.
PMID- 29333064
TI - Colorectal polyposis and inherited colorectal cancer syndromes.
AB - The majority of colorectal cancer (CRC) cases are sporadic, with hereditary
factors contributing to approximately 35% of CRC cases. Less than 5% of CRC is
associated with a known genetic syndrome. Although adenomatous polyposis
syndromes, hamartomatous polyposis syndromes, and those previously classified as
non-polyposis CRC syndromes are quite rare, it is important for clinicians to
know the characteristics of each syndrome and to understand the differences in
cancer risks between the different conditions. This information is very important
when treatment and surveillance plans are formulated for each individual patient.
PMID- 29333065
TI - Hepatitis C infection in patients with hereditary bleeding disorders:
epidemiology, natural history, and management.
AB - Hereditary bleeding disorders include a group of diseases with abnormalities of
coagulation. Prior to 1990, infection with hepatitis C virus (HCV) was mainly
transmitted via pooled plasma products as a treatment for hereditary bleeding
disorders. Anti-HCV positivity in these patients may be as high as >70% in some
areas, while some of them have also been coinfected with human immunodeficiency
virus. Since about 20% of HCV-infected patients clear the infection naturally,
chronic HCV infection represents a significant health problem in this group of
patients. Mortality due to chronic HCV infection is estimated to be >10 times
higher in patients with hemophilia than in the general population, and is mainly
due to liver cirrhosis and hepatocellular carcinoma. The antiviral treatment of
HCV in patients with hereditary bleeding disorders is not different from that of
any other infected patients. Nevertheless, many patients with hereditary bleeding
disorders have declined (Peg)interferon-based treatment because of side effects.
In recent years, multiple orally administrated direct-acting antivirals (DAAs)
have been approved for HCV treatment. Unfortunately, there is not much experience
from treating these patients with DAA regimens, as major studies and real-life
data did not include adequate numbers of patients with inherited hemorrhagic
disorders. However, the available data indicate that DAAs have an excellent
safety profile with a sustained virological response rate of >90%.
PMID- 29333067
TI - Complications of staple line and anastomoses following laparoscopic bariatric
surgery.
AB - With over 600 million people being obese, and given the scientific demonstration
of the advantages of surgical treatment, bariatric surgery is on the rise. The
promising long-term results in terms of weight loss, and particularly in relation
to comorbidities and the control/cure rate, mean that the number of procedures
performed in all countries remains high. However, the risk of potentially complex
or fatal complications, though small, is present and is related to the procedures
per se. This review is a guide for bariatric and/or general surgeons, offering a
complete overview of the pathogenesis of anastomosis and staple line following
the most common laparoscopic bariatric procedures: sleeve gastrectomy, gastric
bypass, and mini-gastric bypass. The review is divided according to the procedure
and the complications (leak, bleeding and stenosis), and evaluates all the
factors that can potentially improve or worsen the complication rate,
representing a "unicum" in the present literature on bariatric surgery.
PMID- 29333069
TI - Comparison of strategies and goals for treatment of chronic constipation among
gastroenterologists and general practitioners.
AB - Background: Although guidelines have been published for the treatment of chronic
constipation, little is known about the actual treatment strategies, the
definitions of drug efficacy, the parameters for drug selection, and the
conceived limitations of the available treatments. The purpose of this study was
to address these issues by comparing treatment strategies among gastroenterology
specialists (GIs) and general practitioners (GPs). Methods: An internet survey
was sent nationwide and at random to GIs and GPs in order to define treatment
strategies, drug efficacy, main parameters for drug selections and the main
limitations of the available drug therapy. Results: Forty GIs and 132 GPs
answered the survey. The maximal sample error was +/-13.4% and +/-8.8%. Treatment
strategies varied considerably between GPs and GIs. The major parameters for drug
selection were related to drug safety among GIs and to clinical outcome among
GPs. The conceived limitations of drug therapy included lack of experience and
unwanted side effects. Conclusions: Awareness of the possible treatment options
and the recommended order of prescription differs between GIs and GPs. There are
still unmet needs for optimizing the treatment for chronic constipation.
PMID- 29333068
TI - Nab-paclitaxel as second-line treatment in advanced gastric cancer: a multicenter
phase II study of the Hellenic Oncology Research Group.
AB - Background: This study evaluated the safety and efficacy of nab-paclitaxel as
second-line treatment in patients with advanced gastric adenocarcinoma. Methods:
Thirty-nine pretreated patients [33 with taxane-based regimens (docetaxel,
cisplatin, and fluorouracil)] and 6 with combination of fluoropyrimidines plus
cisplatin with locally advanced inoperable and metastatic gastric and
gastroesophageal junction adenocarcinoma were treated with weekly nab-paclitaxel
(150 mg/m2 d1, d8, d15 in cycles of 28 days). Results: Partial response (PR) was
documented in nine patients (23.1%; 95% confidence interval 10.1-37.2%), stable
disease (SD) in 11 (28.2%) and disease progression in 18 (46.2%). The disease
control rate (SD + PR + complete response) was 51.3%. Grade 3 and 4 neutropenia
occurred in 10.2% and 5.1% of patients, respectively; grade 3 anemia in 5.1%;
grade 3 neurotoxicity in 5.1%; and grade 2 pain in 5.1%. The median progression
free survival was 3.0 months (range 0.3-13.6) and the median overall survival 6.8
months (range 0.3-22). Conclusion: Nab-paclitaxel as second-line treatment in
locally advanced inoperable or metastatic gastric and gastroesophageal junction
carcinoma is an active chemotherapy regimen with a manageable toxicity profile
and merits further evaluation.
PMID- 29333066
TI - New insights into cholangiocarcinoma: multiple stems and related cell lineages of
origin.
AB - Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies that may
develop at any level of the biliary tree. CCA is currently classified into
intrahepatic (iCCA), perihilar (pCCA) and distal (dCCA) on the basis of its
anatomical location. Notably, although these three CCA subtypes have common
features, they also have important inter- and intra-tumor differences that can
affect their pathogenesis and outcome. A unique feature of CCA is that it
manifests in the hepatic parenchyma or large intrahepatic and extrahepatic bile
ducts, furnished by two distinct stem cell niches: the canals of Hering and the
peribiliary glands, respectively. The complexity of CCA pathogenesis highlights
the need for a multidisciplinary, translational, and systemic approach to this
malignancy. This review focuses on advances in the knowledge of CCA
histomorphology, risk factors, molecular pathogenesis, and subsets of CCA.
PMID- 29333070
TI - Bacterial infections in patients with liver cirrhosis: clinical characteristics
and the role of C-reactive protein.
AB - Background: The diagnosis of bacterial infection in cirrhotic patients may be
difficult, because of the absence of classical signs such as fever and raised
white blood cell count. The role of C-reactive protein (CRP) in this context has
not been clearly defined. Methods: Clinical and laboratory characteristics of 210
consecutive cirrhotic patients with (n=100) or without (n=110) bacterial
infection were compared with a control group of non-cirrhotic patients with
infection (n=106). Results: Significantly fewer patients with cirrhosis had a
body temperature >=37 degrees C when presenting with bacterial infection (56%
cirrhotic vs. 85.5% non-cirrhotic patients, P=0.01). Mean leukocyte count was
6.92 * 103/mm3 in patients with cirrhosis and infection, 5.75 * 103/mm3 (P=0.02)
in cirrhotic patients without infection, and 11.28 * 103/mm3 in non-cirrhotic
patients with infection (P<0.001). Multivariate analysis revealed that CRP level
and model for end-stage liver disease score were significantly associated with
the presence of infection in patients with cirrhosis. A cutoff level of CRP>10
mg/L indicated the presence of infection with a sensitivity of 68%, a specificity
of 84.5% and an area under the receiver operating characteristic curve of 0.8197.
CRP cutoff level differed according to the severity of the liver disease: Child
Pugh score (CPS) A: 21.3 mg/L, B: 17 mg/L, and C: 5.78 mg/L. Conclusions: CRP at
admission could help diagnose infection in cirrhotic patients. Since the severity
of liver disease seems to affect the CRP values, lower CRP levels might indicate
infection. Clinical suspicion is necessary to avoid delay in diagnosis and
initiate antibiotic treatment.
PMID- 29333071
TI - Factors associated with waiting time on the liver transplant list: an analysis of
the United Network for Organ Sharing (UNOS) database.
AB - Background: Liver transplantation (LT) is an important treatment for acute liver
failure and end-stage liver disease. In 2002, the model for end-stage liver
disease (MELD) score was incorporated to prioritize patients awaiting LT.
Although there is data on how the MELD score affects waiting times, there is a
paucity of literature regarding other components. We aimed to evaluate the
factors affecting LT waiting times in the United States. Methods: Using the
United Network for Organ Sharing (UNOS) database, patients aged 12-75 years
listed for LT over the years 2002-2015 were included. Variables tested in the
model included patient characteristics, pertinent laboratory values, ABO blood
type, region of listing, primary payer, ethnicity, and listing for simultaneous
transplantation. Results: A total of 75,771 patients were included in the final
analysis. The components of the MELD score were associated with shorter waiting
times. Other factors associated with shorter waiting times were the need of
mechanical ventilation and region 3 of transplantation. ABO blood type, primary
payer, and placement of a transjugular intrahepatic porto-systemic shunt also
influenced time on the LT waiting list. Conclusions: MELD score is utilized in
the prioritization of liver allocation, and was expected to predict waiting-list
time. Mechanical ventilation and other markers of disease severity are associated
with higher MELD scores and thus shorter waiting times. Further research is
needed to address reasons for the variation in waiting times between regions and
payment systems in an attempt to decrease time to LT, standardize the listing
process, and improve patient outcomes.
PMID- 29333073
TI - The impact of age on the incidence and severity of post-endoscopic retrograde
cholangiopancreatography pancreatitis.
AB - Background: With advancing age there is progressive pancreatic atrophy and
fibrosis, leading to tissue destruction and chronic pancreatitis that has been
found to be protective against post-endoscopic retrograde
cholangiopancreatography (ERCP) pancreatitis (PEP). However, there are no reports
regarding the potential effect of the aging pancreatic changes on the incidence
and severity of PEP. Therefore, the aim of the present study was to investigate
the impact of senile changes in the pancreas on the incidence and severity of
PEP. Methods: A total of 2688 patients who underwent the first therapeutic ERCP
at a single center were included in the final analysis of the study. Patients
were classified into two groups: 1644 patients aged <=75 years (mean age
61.56+1.26 years), group A; and 1044 patients aged >75 years (mean age 81.97+4.29
years), group B. Patients' files were identified using a retrospective database
linked to the endoscopy reporting system. Patients' characteristic, endoscopic
findings, details of intervention and rate and severity of PEP were evaluated.
Results: No significant differences between the two groups were observed with
regard to ERCP indication, patient- and technique-related risk factors for PEP,
presence of periampullary diverticulum, and type of therapeutic intervention. The
incidence of PEP was 5.2% in group A and 4% in group B (P=NS) with comparable
grades of severity. All episodes of pancreatitis had full recovery with
conventional treatment. One death occurred from respiratory arrest in each group
of patients. Conclusion: This study shows that the pancreatic changes associated
with aging do not influence the incidence and severity of PEP.
PMID- 29333072
TI - Prevalence of incidental pancreatic cyst on upper endoscopic ultrasound.
AB - Background: This study aimed to determine the prevalence of incidental pancreatic
cysts in patients undergoing upper endoscopic ultrasound without a known
pancreatic abnormality. Methods: This prospective study was conducted in two
hospitals in Spain and enrolled consecutive patients referred for upper
endoscopic ultrasound for a condition unrelated to the pancreas. Patients with a
previous pancreatic anomaly, history of acute or chronic pancreatitis, evidence
of acute pancreatitis, previous upper gastrointestinal surgery, or chronic
abdominal pain suggestive of pancreatic origin were excluded. Univariate logistic
regression was performed to evaluate individual covariates and the incidental
pancreatic cyst risk. Results: A total of 298 patients were included, of whom 64
had pancreatic cysts (21.5%; 16.9-26.6%). The mean size of the cysts was 6.3+/
3.7 (range 3-25) mm. Six cysts (2%) were >10 mm and 16 (5.4%) were compatible
with branch duct intraductal papillary mucinous neoplasm. The pancreatic cyst
prevalence was similar in the two hospitals and increased significantly with age.
Conclusion: The prevalence of incidental pancreatic cysts during endoscopic
ultrasound was very high in our study population.
PMID- 29333074
TI - Laparoendoscopic rendezvous may be an effective alternative to a failed
preoperative endoscopic retrograde cholangiopancreatography in patients with
cholecystocholedocholithiasis.
AB - Background: Endoscopic retrograde cholangiopancreatography (ERCP), followed by
laparoscopic cholecystectomy (LC), remains the standard way of management for
patients with cholecystocholedocholithiasis. Laparoendoscopic rendezvous (LERV),
a combined procedure for removing the gallbladder laparoscopically and clearing
the common bile duct (CBD) endoscopically at the same time, could be an
attractive alternative. The aim of this study was to compare LERV with classic
ERCP in patients with cholecystocholedocholithiasis. Methods: 886 patients with
cholecystocholedocholithiasis were treated either with the LERV technique (90
patients), or with the 2-stage approach, which includes preoperative ERCP
followed by LC (796 patients). The primary endpoint was any difference in the
success of CBD cannulation and clearance; secondary endpoints were the detection
of differences in morbidity (especially post-ERCP pancreatitis [PEP]), and the
feasibility of the two approaches. Results: Successful cannulation of the CBD was
more frequent with conventional ERCP compared with the LERV technique (89.8% vs.
75.5%, P=0.0001). LERV appears to be as effective as conventional ERCP for
complete CBD clearance (85.5% vs. 82.8%, P<0.1). None of the patients in the LERV
group had an episode of clinical PEP, whereas in the conventional ERCP group
there were 23 episodes of PEP and one death. The median amylase level was higher
in patients undergoing conventional ERCP group compared to patients in LERV
group. Conclusion: Classic ERCP has a higher rate of successful CBD cannulation
and a similar rate of CBD clearance compared to LERV.
PMID- 29333075
TI - Safety and efficacy of extending a previous endoscopic sphincterotomy for the
treatment of retained or recurrent common bile duct stones.
AB - Background: The aim of the study was to evaluate the safety and efficacy of
extending a previous endoscopic sphincterotomy (ES) in patients with retained or
recurrent common bile duct (CBD) stones. Methods: Between 2001 and 2013,
extension of a previous ES, for known or suspected CBD stones, was performed in
118 patients (m/f, 53/65) with a median age of 74 (range: 31-91) years (group A).
During the same period, ES was performed in 1064 patients with suspected or known
choledocholithiasis (group B). The efficacy and complications of the extension
(group A) were analyzed and a comparison was made between groups regarding
complications. Results: Bile duct cannulation was straightforward in all patients
in group A, while it was considered difficult in 49% of patients in group B.
Complete clearance was achieved in 76/97 patients (78%) with CBD stones, after a
mean of 1.18 attempts per patient. Mechanical lithotripsy was required in 10% of
patients. After extension, immediate bleeding occurred in 24 patients (20%),
which stopped spontaneously in 9 (37%) and endoscopic hemostasis was required in
the remainder. Complications were more frequent in group B (5.3% vs. 0.8%,
P=0.031), but there was no significant difference for any individual
complication. Immediate bleeding was more common in group B (29% vs. 20%,
P=0.035), but there was no difference in clinical bleeding. Conclusion: Extension
of a previous ES seems to be a simple, effective and safe technique, allowing
stone clearance in nearly 80% of patients; it is thus recommended in patients
with CBD stones after ES.
PMID- 29333077
TI - Underwater endoclip closure after endoscopic resection for duodenal adenomas.
PMID- 29333076
TI - Parenchyma-sparing hepatectomy (PSH) versus non-PSH for bilobar liver metastases
of colorectal cancer.
AB - Background: Preoperative interventions have increased the resectability of
colorectal cancer (CRC) liver metastases. This retrospective study compares
outcomes after liver resection for bilobar CRC metastases between patients who
underwent parenchyma-sparing hepatectomy (PSH), i.e., segmentectomies and smaller
resections on both lobes, and those treated with non-PSH, i.e., hemihepatectomy
plus any resection on the other lobe. Methods: A cohort of 119 patients who
underwent liver resection for bilobar CRC metastases were included. Perioperative
course and long-term survival were compared between 59 patients who underwent PSH
and 60 patients who underwent non-PSH. Statistical analyses were done using
Pearson's chi-square test, Fisher's exact test and the Mann-Whitney U test.
Overall survival analysis was performed by the Kaplan-Meier estimator and Cox
regression analysis. Results: The median number of liver metastases was 2 in
patients treated with PSH and 3 in those treated with non-PSH (P<0.01).
Postoperative mortality, severe complications and radicality did not differ
significantly between groups. Median intraoperative bleeding was 250 mL for PSH
and 600 mL for non-PSH (P<0.001). Median operation time and hospital stay were
significantly shorter for PSH. Overall survival was comparable between groups,
also after adjustment for covariates. Conclusions: There were no significant
differences in outcome, except for differences in bleeding, operation time and
postoperative stay, favoring PSH. Furthermore, minimizing resection did not
influence radicality. Hence, this study supports the use of PSH for bilobar CRC
liver metastases when possible.
PMID- 29333078
TI - Acute pancreatitis caused by cytomegalovirus-associated duodenal papillitis.
PMID- 29333079
TI - Type 1 autoimmune hepatitis presenting with severe autoimmune neutropenia.
AB - Autoimmune hepatitis (AIH) is a progressive, chronic liver disease characterized
by unresolving hepatocellular inflammation of autoimmune origin. The clinical
spectrum may vary from asymptomatic presentation, to non-specific symptoms such
as fatigue, arthralgias, nausea and abdominal pain, to acute severe liver
disease. AIH is characterized by the presence of interface hepatitis and portal
plasma cell infiltration on histological examination, hypergammaglobulinemia, and
positive autoantibodies. AIH is associated with other autoimmune diseases and its
course is often accompanied by various non-specific hematological disorders.
However, the coexistence of autoimmune neutropenia (AIN) is infrequent. We
present a case of a female patient diagnosed with type 1 AIH and agranulocytosis
on presentation. A diagnosis of AIN was established, based on the patient's sex,
the underlying liver disease, the absence of alternative causes, the presence of
atypical anti-neutrophil cytoplasmic antibodies in patient's serum and the
favorable and dose-dependent treatment of both pathologic entities with
corticosteroids and mycophenolate mofetil.
PMID- 29333080
TI - Comparisons of Traffic-Related Ultrafine Particle Number Concentrations Measured
in Two Urban Areas by Central, Residential, and Mobile Monitoring.
AB - Traffic-related ultrafine particles (UFP; <100 nanometers diameter) are
ubiquitous in urban air. While studies have shown that UFP are toxic,
epidemiological evidence of health effects, which is needed to inform risk
assessment at the population scale, is limited due to challenges of accurately
estimating UFP exposures. Epidemiologic studies often use empirical models to
estimate UFP exposures; however, the monitoring strategies upon which the models
are based have varied between studies. Our study compares particle number
concentrations (PNC; a proxy for UFP) measured by three different monitoring
approaches (central-site, short-term residential-site, and mobile on-road
monitoring) in two study areas in metropolitan Boston (MA, USA). Our objectives
were to quantify ambient PNC differences between the three monitoring platforms,
compare the temporal patterns and the spatial heterogeneity of PNC between the
monitoring platforms, and identify factors that affect correlations across the
platforms. We collected >12,000 hours of measurements at the central sites, 1,000
hours of measurements at each of 20 residential sites in the two study areas, and
>120 hours of mobile measurements over the course of ~1 year in each study area.
Our results show differences between the monitoring strategies: mean one-minute
PNC on-roads were higher (64,000 and 32,000 particles/cm3 in Boston and Chelsea,
respectively) compared to central-site measurements (23,000 and 19,000
particles/cm3) and both were higher than at residences (14,000 and 15,000
particles/cm3). Temporal correlations and spatial heterogeneity also differed
between the platforms. Temporal correlations were generally highest between
central and residential sites, and lowest between central-site and on-road
measurements. We observed the greatest spatial heterogeneity across monitoring
platforms during the morning rush hours (06:00-09:00) and the lowest during the
overnight hours (18:00-06:00). Longer averaging times (days and hours vs.
minutes) increased temporal correlations (Pearson correlations were 0.69 and 0.60
vs. 0.39 in Boston; 0.71 and 0.61 vs. 0.45 in Chelsea) and reduced spatial
heterogeneity (coefficients of divergence were 0.24 and 0.29 vs. 0.33 in Boston;
0.20 and 0.27 vs. 0.31 in Chelsea). Our results suggest that combining stationary
and mobile monitoring may lead to improved characterization of UFP in urban areas
and thereby lead to improved exposure assignment for epidemiology studies.
PMID- 29333081
TI - Innate immunity recovers earlier than acquired immunity during severe
postoperative immunosuppression.
AB - Background: Postoperative immune suppression, particularly a loss of cell
mediated immunity, is commonly seen after surgery and is associated with worse
outcome, i.e. delayed wound healing, infections, sepsis, multiple-organ failure
and cancer recurrence. However, the recovery of immune cells focusing on
differences between innate and acquired immunity during severe postoperative
immunosuppression is not investigated. Methods: In this retrospective randomized
controlled trial (RCT) subgroup analysis, 10 postoperatively immune suppressed
patients after esophageal or pancreatic resection were analyzed. Innate and
acquired immune cells, the expression of human leukocyte antigen-D related on
monocytes (mHLA-DR), lipopolysaccharide (LPS)-induced monocytic TNF-alpha and IL
10 secretion ex vivo, Concanavalin A (Con A)-induced IFN-gamma, TNF-alpha, IL-2,
IL-4, IL-5 and IL-10 release were measured preoperatively (od) until day 5 after
surgery (pod5). Recovery of immune cells was defined by a significant decrease
respectively increase after a significant postoperative alteration. Statistical
analyses were performed using nonparametric statistical procedures. Results:
Postoperative alterations of innate immune cells recovered on pod2 (eosinophils),
pod3 (neutrophils) and pod5 (mHLA-DR, monocytic TNF-alpha and IL-10 secretion),
whereas alterations of acquired immune cells (lymphocytes, T cells, T helper
cells, and cytotoxic T cells) did not recover until pod5. Peripheral blood T
cells showed an impaired production of the T helper (Th) 1 cytokine IFN-gamma
upon Con A stimulation on pod1, while Th2 specific cytokine release did not
change until pod5.Conclusions: Innate immunity recovered earlier than acquired
immunity during severe postoperative immunosuppression. Furthermore, we found a
more anti- than pro-inflammatory T cell function on the first day after surgery,
while T cell counts decreased.
PMID- 29333082
TI - A FCGR3A Polymorphism Predicts Anti-drug Antibodies in Chronic Inflammatory Bowel
Disease Patients Treated With Anti-TNF.
AB - BACKGROUND: The production of anti-drug antibodies (ADAs) against IgG monoclonal
antibodies (mAbs) targeting tumour necrosis factor (TNF) is an important cause of
loss of response to anti-TNF mAbs in patients with inflammatory bowel diseases
(IBD) such as Crohn's disease (CD) and ulcerative colitis (UC). Since receptors
for the Fc portion of IgG (FCGRs) are involved in the degradation of IgG
complexes, we hypothesised that a polymorphism in FCGR3A (V158F; rs396991) gene
could be involved in anti-TNF ADA generation and treatment resistance. MATERIAL
AND METHODS: A cohort of 103 IBD patients (80 CD, 23 UC) were genotyped and serum
level of both anti-TNFs (infliximab or adalimumab) and ADA against them were
measured. RESULTS: No significant differences were observed between ADA
occurrence or V158F genotype and type of disease or the kind of anti-TNF
administrated. Interestingly, VV genotype correlated with patients producing ADA
(VV: 37.5% vs. FV: 10.6% or FF: 5%; p=0.004) and was an independent predictor of
this event after multivariate analysis. Moreover, VV genotype also correlated
with those patients receiving anti-TNF dose intensification (p=0.03). CONCLUSION:
FCGR3A V158F polymorphism seems to be associated with ADA production against mAbs
and it could be taken into account when considering the dose and type of anti-TNF
in IBD patients.
PMID- 29333083
TI - Optimal Load for Bone Tissue Scaffolds with an Assigned Geometry.
AB - Thanks to the recent advances of three-dimensional printing technologies the
design and the fabrication of a large variety of scaffold geometries was made
possible. The surgeon has the availability of a wide number of scaffold micro
architectures thus needing adequate guidelines for the choice of the best one to
be implanted in a patient-specific anatomic region. We propose a mechanobiology
based optimization algorithm capable of determining, for bone tissue scaffolds
with an assigned geometry, the optimal value Lopt of the compression load to
which they should be subjected, i.e. the load value for which the formation of
the largest amounts of bone is favoured and hence the successful outcome of the
scaffold implantation procedure is guaranteed. Scaffolds based on hexahedron unit
cells were investigated including pores differently dimensioned and with
different shapes such as elliptic or rectangular. The algorithm predicted
decreasing values of the optimal load for scaffolds with pores with increasing
dimensions. The optimal values predicted for the scaffolds with elliptic pores
were found higher than those with rectangular ones. The proposed algorithm can be
utilized to properly guide the surgeon in the choice of the best scaffold
type/geometry that better satisfies the specific patient requirements.
PMID- 29333084
TI - Effects of alpha-Mangostin on Viability, Growth and Cohesion of Multicellular
Spheroids Derived from Human Breast Cancer Cell Lines.
AB - Background: alpha-Mangostin (alphaMG) is extracted from Garcinia mangostana Linn
and exerts antiproliferative activities. Although several researches on alphaMG
were performed using cell monolayers, the in vitro pharmacological effects on 3D
cancer models have never been investigated. Aim of the present study was to find
new anticancer properties of alphaMG by evaluating the changes that this compound
provokes in multicellular tumour spheroids (MCTSs). Methods: MCTSs were generated
from MDA-MB-231 and MCF-7 breast tumour cell lines and then treated with 0.1/30
MUg/ml alphaMG for 24 and 48 h. MCTS size, density, and cell migration were
determined by software elaboration of phase contrast images captured by a digital
camera. Cell viability was evaluated by resazurin and acid phosphatase assays,
while cell apoptosis was assessed by a fluorescent assay of caspase activity. The
distribution of living cells inside MCTSs was shown by live/dead fluorescence
staining. Results: A dose-dependent decrease in cell viability was obtained by
treating MDA-MB-231 spheroids with alphaMG for 48 h (IC50 = 0.70-1.25 MUg/ml). A
significant reduction in spheroid volume, paralleled by its increased
compactness, was observed only at concentration of 30 MUg/ml, but not with lower
doses of alphaMG. By contrast, alphaMG in the range of 5-15 MUg/ml increased the
size of MCTSs due to a parallel reduction in cell aggregation. The same window of
concentrations was also able to stimulate cell apoptosis in a dose-dependent
manner. Bimodal volumetric effects were also obtained by treating the spheroids
generated from the MCF-7 cells with 0.1/30 MUg/ml alphaMG for 48 h. Finally,
doses higher than 5 MUg/ml caused a progressive impairment in cell migration from
the edge of MDA-MB-231 MCTSs. Conclusion: After exposure at doses of alphaMG just
above IC50, MDA-MB-231 spheroids showed a significant reduction in cell adhesion
that did not stimulate cell migration but, on the contrary, blunted cell
motility. These findings suggest a novel anticancer feature of alphaMG that could
be taken into consideration to improve conventional drug penetration into the
tumour bulk.
PMID- 29333085
TI - Next Generation Sequencing expression profiling of mitochondrial subunits in men
with Klinefelter syndrome.
AB - Objectives: Klinefelter syndrome (KS) is one of the most common sex-chromosome
disorders as it affects up to 1 in every 600-1000 newborn males. Men with KS
carry one extra X chromosome and they usually present a 47,XXY karyotype, but
less frequent variants have also been reported in literature. KS typical symptoms
include tall stature, gynecomastia, broad hips, hypogonadism and absent
spermatogenesis. The syndrome is also related to a wide range of cognitive
deficits, among which language-based learning disabilities and verbal cognition
impairment are frequently diagnosed. The present study was carried out to
investigate the role of mitochondrial subunits in KS, since the molecular
mechanisms underlying KS pathogenesis are not fully understood. Methods: The
study was performed by the next generation sequencing analysis and qRT-PCR assay.
Results: We were able to identify a significant down-expression of mitochondrial
encoded NADH: ubiquinone oxidoreductase core subunit 6 (MT-ND6) in men with KS.
Conclusion: It is known that defects of the mtDNA encoding mitochondrial subunits
are responsible for the malfunction of Complex I, which will eventually lead to
the Complex I deficiency, the most common respiratory chain defect in human
disorders. Since it has been shown that decreased Complex I protein levels could
induce apoptosis, wehypothesizethat the above-mentioned MT-ND6 down-expression
contributes to the wide range of phenotypes observed in men with KS.
PMID- 29333087
TI - Antioxydation And Cell Migration Genes Are Identified as Potential Therapeutic
Targets in Basal-Like and BRCA1 Mutated Breast Cancer Cell Lines.
AB - Basal-like breast cancers are among the most aggressive cancers and effective
targeted therapies are still missing. In order to identify new therapeutic
targets, we performed Methyl-Seq and RNA-Seq of 10 breast cancer cell lines with
different phenotypes. We confirmed that breast cancer subtypes cluster the RNA
Seq data but not the Methyl-Seq data. Basal-like tumor hypermethylated phenotype
was not confirmed in our study but RNA-Seq analysis allowed to identify 77 genes
significantly overexpressed in basal-like breast cancer cell lines. Among them,
48 were overexpressed in triple negative breast cancers of TCGA data. Some
molecular functions were overrepresented in this candidate gene list. Genes
involved in antioxydation, such as SOD1, MGST3 and PRDX or cadherin-binding
genes, such as PFN1, ITGB1 and ANXA1, could thus be considered as basal like
breast cancer biomarkers. We then sought if these genes were linked to BRCA1,
since this gene is often inactivated in basal-like breast cancers. Nine genes
were identified overexpressed in both basal-like breast cancer cells and BRCA1
mutated cells. Amongst them, at least 3 genes code for proteins implicated in
epithelial cell migration and epithelial to mesenchymal transition (VIM, ITGB1
and RhoA). Our study provided several potential therapeutic targets for triple
negative and BRCA1 mutated breast cancers. It seems that migration and
mesenchymal properties acquisition of basal-like breast cancer cells is a key
functional pathway in these tumors with a high metastatic potential.
PMID- 29333086
TI - Ethical and Safety Issues of Stem Cell-Based Therapy.
AB - Results obtained from completed and on-going clinical studies indicate huge
therapeutic potential of stem cell-based therapy in the treatment of
degenerative, autoimmune and genetic disorders. However, clinical application of
stem cells raises numerous ethical and safety concerns. In this review, we
provide an overview of the most important ethical issues in stem cell therapy, as
a contribution to the controversial debate about their clinical usage in
regenerative and transplantation medicine. We describe ethical challenges
regarding human embryonic stem cell (hESC) research, emphasizing that ethical
dilemma involving the destruction of a human embryo is a major factor that may
have limited the development of hESC-based clinical therapies. With previous
derivation of induced pluripotent stem cells (iPSCs) this problem has been
overcome, however current perspectives regarding clinical translation of iPSCs
still remain. Unlimited differentiation potential of iPSCs which can be used in
human reproductive cloning, as a risk for generation of genetically engineered
human embryos and human-animal chimeras, is major ethical issue, while undesired
differentiation and malignant transformation are major safety issues. Although
clinical application of mesenchymal stem cells (MSCs) has shown beneficial
effects in the therapy of autoimmune and chronic inflammatory diseases, the
ability to promote tumor growth and metastasis and overestimated therapeutic
potential of MSCs still provide concerns for the field of regenerative medicine.
This review offers stem cell scientists, clinicians and patient's useful
information and could be used as a starting point for more in-depth analysis of
ethical and safety issues related to clinical application of stem cells.
PMID- 29333088
TI - Bone Regeneration using Silk Hydroxyapatite Hybrid Composite in a Rat Alveolar
Defect Model.
AB - Background: To overcome the limited source of autogenous bone in bone grafting,
many efforts have been made to find bone substitutes. The use of hybrid
composites of silk and hydroxyapatite to simulate natural bone tissue can
overcome the softness and brittleness of the individual components. Methods:
Critical-sized, 7 x 4 x 1.5 mm alveolar defects were created surgically in 36
Sprague-Dawley rats. Three treatment groups were tested: an empty defect group
(group I), a silk fibrin scaffold group (group II), and a hydroxyapatite
conjugated silk fibrin scaffold group (group III). New bone formation was
assessed using computed tomography and histology at 4, 8, and 12 weeks, and semi
quantitative western blot analysis was done to confirm bone protein formation at
12weeks. Statistical analysis of new bone formation was done using the Kruskal
Wallis test. Results: Radiomorphometric volume analysis revealed that new bone
formation was 64.5% in group I, 77.4% in group II, and 84.8% in group III
(p=0.027) at 12 weeks. Histologically, the osteoid tissues were surrounded by
osteoblasts not only at the border of the bone defect but in the center of the
scaffold implanted area in group III from week 8 on. Semi-quantitative western
blotting revealed that osteocalcin expression in group III was 1.8 times higher
than group II and 2.6 times higher than group I. Conclusions: New bone formation
was higher in hybrid scaffolds. Both osteoconduction at the defect margin and
osteoinduction at the center of the defect were confirmed. There were no detected
complications related to foreign body implantation.
PMID- 29333089
TI - Lentivirus-mediated shRNA Targeting CNN2 Inhibits Hepatocarcinoma in Vitro and in
Vivo.
AB - Objective: Hepatocellular carcinoma (HCC) is one of the most common malignant
tumors with a high rate of mortality. Our previous study shows the expression of
calponin 2 (CNN2) is up-regulated in hepatocellular carcinoma tissues, especially
in metastatic ones. To better understand the role of CNN2 in HCC, RNA
interference (RNAi) was used to explore its role in tumor growth and metastasis.
Methods: Lentivirus-mediated CNN2-shRNA was transfected into SK-hep-1 cells, and
the efficacy of CNN2 expression, cell migration, invasion, proliferation and cell
cycles were evaluated by quantitative real-time polymerase chain reaction (qRT
PCR), Western blot (WB), Transwell assay, methyl thiazol tetrazolium assay and
flow cytometry, respectively. SK-hep-1 cells transfected with Lentivirus-CNN2
shRNA were xenografted in Balb/C nude mice to explore the effect of CNN2-shRNA in
tumor growth. Xenograft tumor tissues were examined for their histopathology,
cell apoptosis, the expression of total protein and their corresponding
phosphorylated protein of MEK1/2, ERK1/2, AKT, by hematoxylin and eosin stain (H
& E staining), TUNEL assay, immunohistochemical technique, respectively. Results:
Our research shows it is evident that CNN2 shRNA can effectively down-regulate
the expressions of CNN2 mRNA and protein, inhibit cell proliferations, arrest
cell cycles at the S phase and reduce cell migration and invasion. SK-hep-1 cells
with CNN2 down-regulation have markedly attenuated tumor growth in nude mice.
Xenograft tumor tissues have displayed typical tumor characteristics and no
apoptosis is detected in shRNA group or in control group. No metastatic tumor was
found in any group of nude mice. With CNN2 protein down-regulation, the protein
of pMEK1/2 and pERK1/2 are effectively down-regulated, except pAKT, AKT, MEK1/2
and ERK1/2. Conclusions: CNN2 plays an important role in tumor growth and
metastasis, possibly through MEK1/2-ERK1/2 signaling pathway. Our study
illustrate that CNN2 might be a potential target in HCC molecular target therapy.
PMID- 29333090
TI - Gene and Protein Expression Profiles in a Mouse Model of Collagen-Induced
Arthritis.
AB - The risk of rheumatoid arthritis (RA), an autoimmune disease, in the elderly
population increases along with that of atherosclerosis, cardiovascular disease,
type 2 diabetes, and Alzheimer's disease. Identifying specific biomarkers for RA
can clarify the underlying molecular mechanisms and can aid diagnosis and patient
care. To this end, the present study investigated the genes and proteins that are
differentially expressed in RA using a mouse collagen-induced arthritis (CIA)
model. We performed gene microarray and proteome array analyses using blood
samples from the mice and found that 50 genes and 24 proteins were upregulated
and 48 genes were downregulated by more than 2-fold in the CIA model relative to
the control. The gene microarray and proteome array results were validated by
evaluating the expression levels of select genes and proteins by real-time PCR
and western blotting, respectively. We found that the level of integrin alpha2,
which has not been previously reported as a biomarker of RA, was significantly
increased in CIA mice as compared to controls. These findings provide a set of
novel biomarkers that can be useful for diagnosing and evaluating the progression
of RA.
PMID- 29333091
TI - In vitro and in vivo effects of miRNA-19b/20a/92a on gastric cancer stem cells
and the related mechanism.
AB - We aimed to analyze the in vitro and in vivo effects of miRNA-19b/20a/92a on
gastric cancer stem cells (GCSCs) and the related mechanism. GCSCs were cultured
until adherence and differentiation, and subjected to miRNA microarray analysis
to find and to verify miRNA deletion. Cells stably expressing lentivirus carrying
miRNA-19b/20a/92a were constructed by transfection. The relationship between
miRNA-19b/20a/92a and renewal of GCSCs was studied by the tumor sphere assay, and
that between miRNA-19b/20a/92a and their proliferation was explored with MTT and
colony formation assays. Target genes of miRNA for promoting the proliferation
and self-renewal of GCSCs were found by using bioinformatics database, and
verified by the reporter gene assay and Western blot. The expressions of miRNA
19b/20a/92a gradually decreased during the adherence and differentiation of
GCSCs. The expressions of lentivirus carrying miRNA-17-19 gene in MKN28 and CD44
/EpCAM- cells were increased significantly. Transient transfection with pre-miRNA
19b/20a/92a elevated miRNA expressions in CD44-/EpCAM- and MKN28 cells, whereas
transfection with pre-miRNA-19b/20a/92a antagonists reduced the expressions in
SGC7901 and CD44+/EpCAM+ cells. Overexpression of lenti-miRNA-19b/20a/92a
significantly enhanced the capability of GCSCs to form tumor spheres. In the
presence of chemotherapeutic agent, the survival of lenti-miRNA-19b/20a/92a
infected cells was prolonged. Transient transfection with pre-miRNA-19b/20a/92a
significantly increased the number of CD44+/EpCAM+ cells, but transfection with
antagonists had the opposite outcomes. The stable miRNA-19b/20a/92a expression
groups proliferated faster than the control group did. The proliferation of cells
transfected with pre-miRNA-19b/20a/92a was accelerated, whereas that of cells
transfected with the antagonists was decelerated. Compared with the control
group, the number of colonies in the former group was higher, but that in the
latter group was lower. miRNA-19b and miRNA-92a could bind the 3' untranslated
region of HIPK1, while miRNA-20a was able to bind that of E2F1. Expressions of
miRNA-20a and miRNA-92a in gastric cancer samples were negatively correlated with
the prognosis of patients. miRNA-19b/20a/92a facilitated the self-renewal of
GCSCs by targeting E2F1 and HIPK1 on the post-transcriptional level and
activating the beta-catenin signal transduction pathway. miRNA-92a was an
independent factor and index predicting the prognosis of gastric cancer.
PMID- 29333092
TI - Role of APOBEC3H in the Viral Control of HIV Elite Controller Patients.
AB - Background APOBEC3H (A3H) gene presents variation at 2 positions (rs139297 and
rs79323350) leading to a non-functional protein. So far, there is no information
on the role played by A3H in spontaneous control of HIV. The aim of this study
was to evaluate the A3H polymorphisms distribution in a well-characterized group
of Elite Controller (EC) subjects. Methods We analyzed the genotype distribution
of two different SNPs (rs139297 and rs79323350) of A3H in 30 EC patients and
compared with 11 non-controller (NC) HIV patients. Genotyping was performed by
PCR, cloning and Sanger sequencing. Both polymorphisms were analyzed jointly in
order to adequately attribute the active or inactive status of A3H protein.
Results EC subjects included in this study were able to maintain a long-term
sustained spontaneous HIV-viral control and optimal CD4-T-cell counts; however,
haplotypes leading to an active protein were very poorly represented in these
patients. We found that the majority of EC subjects (23/30; 77%) presented
allelic combinations leading to an inactive A3H protein, a frequency slightly
lower than that observed for NC studied patients (10/11; 91%). Conclusions The
high prevalence of non-functional protein coding-genotypes in EC subjects seems
to indicate that other innate restriction factors different from APOBEC3H could
be implicated in the replication control exhibited by these subjects.
PMID- 29333093
TI - Bactericidal effects of deep ultraviolet light-emitting diode for solutions
during intravenous infusion.
AB - Background: Ultraviolet irradiation is effectively used as a disinfection method
for inactivating microorganisms. Methods: We investigated the bactericidal
effects by irradiation with a deep-ultraviolet light-emitting diode (DUV-LED) on
the causative microorganisms of catheter related blood stream infection
contaminating the solution for intravenous infusion. For irradiation, prototype
modules for water disinfection with a DUV-LED were used. Experiments were
conducted on five kinds of microorganisms. We examined the dependence of
bactericidal action on eleven solutions. Administration sets were carried out
three types. Results: When the administration set JY-PB343L containing the
infusion tube made of polybutadiene was used, the bactericidal action of the DUV
LED against all tested microorganisms in the physiological saline solutions was
considered to be effective. We confirmed that the number of viable bacteria
decreased in 5% glucose solution and electrolyte infusions with DUV-LED
irradiation. Conclusions: These results indicate that the DUV-LED irradiation has
bactericidal effects in glucose infusion and electrolyte infusions by irradiating
via a plasticizer-free polybutadiene administration set. We consider DUV-LED
irradiation to be clinically applicable.
PMID- 29333094
TI - Left ventricular diastolic and systolic dyssynchrony and dysfunction in heart
failure with preserved ejection fraction and a narrow QRS complex.
AB - Aims: Mechanical dyssynchrony has been reported in heart failure with preserved
ejection fraction (HFpEF), with a majority of patients having a narrow QRS
complex; however, whether any benefit is observed with restoration of
dyssynchrony remains unclear. We sought to assess left ventricular (LV)
dyssynchrony and function in HFpEF and elucidate the underlying mechanisms that
may account for HFpEF. Methods: Seventy-eighty patients with a narrow QRS complex
including 47 with HFpEF, 31 with heart failure with reduced ejection fraction
(HFrEF) patients, and 29 with asymptomatic left ventricular diastolic dysfunction
(LVDD) were recruited. Forty-five normal subjects acted as controls. Systolic LV
longitudinal strain (LS), systolic longitudinal strain rate (LSrS), early
diastolic longitudinal strain rate (LSrE), and late diastolic longitudinal strain
rate (LSrA) were measured using speckle tracking echocardiography. LV diastolic
and systolic dyssynchrony (Te-SD and Ts-SD) were calculated. Results: Te-SD and
Ts-SD were prolonged in HFpEF and HFrEF patients than in the control group
(p<0.05). However, Ts-SD was shorter in HFpEF patients compared to HFrEF patients
despite a narrow QRS complex (p<0.05). LV global LS, LSrS, and LSrE were
decreased in patients with HFpEF and HFrEF compared to other groups, with HFrEF
being even more reduced than HFpEF (p<0.05). Reduced LS, LSrS, and LSrE could
effectively differentiate HF from asymptomatic LVDD patients (p<0.05).
Conclusion: HFrEF exhibited increased systolic dyssynchrony compared to HFpEF
despite a narrow QRS complex in addition to the more reduced diastolic and
systolic function. Therefore, targeting to improve diastolic and systolic
function instead of managing systolic dyssynchrony might be of great importance
in the treatment of HFpEF.
PMID- 29333095
TI - Cinnamomum Cassia Extracts Suppress Human Lung Cancer Cells Invasion by Reducing
u-PA/MMP Expression through the FAK to ERK Pathways.
AB - Cinnamomum cassia exhibits antioxidative, apoptotic, and cytostatic properties.
These activities have been attributed to the modulation of several biological
processes and are beneficial for possible pharmaceutical applications. However,
the potential of C. cassia in retarding lung adenocarcinoma cells metastasis
remains ambiguous. We determined whether C. cassia extract (CCE) reduces
metastasis of human lung adenocarcinoma cells. The results showed that CCE
treatment (up to 60 MUg/mL) for 24 h exhibited no cytotoxicity on the A549 and
H1299 cell lines but inhibited the motility, invasiveness, and migration of these
cells by repressing matrix metalloproteinase (MMP)-2 and urokinase-type
plasminogen activator (u-PA). CCE also impaired cell adhesion to collagen. CCE
significantly reduced p-focal adhesion kinase (FAK) Tyr397, p-FAK Tyr925, p
extracellular signal-regulated kinases (ERK)1/2, and Ras homolog gene family
(Rho)A expression. CCE showed anti-metastatic activity of A549 and H1299 cells by
repressing u-PA/MMP-2 via FAK to ERK1/2 pathways. These findings may facilitate
future clinical trials of lung adenocarcinoma chemotherapy to confirm the
promising results.
PMID- 29333096
TI - Analysis of MED12 Mutation in Multiple Uterine Leiomyomas in South Korean
patients.
AB - Uterine leiomyomas are one of the most common benign gynecologic tumors, but the
exact causes are not completely understood. In 2011, through DNA sequencing,
MED12 mutation was discovered in approximately 71% of uterine leiomyomas. Several
recent studies confirmed the high frequency of MED12 mutation in uterine
leiomyoma. Nevertheless, no study has been done on MED12 mutation in the case of
patients with multiple leiomyomas in a patient. The purpose of this study was to
investigate the frequency of MED12 mutations in uterine leiomyomas of South
Korean patients. In addition, we examined MED12 mutation in multiple leiomyomas
in the same patients. Uterine leiomyoma tissues were obtained from symptomatic
women who underwent hysterectomy or myomectomy for medically indicated reasons.
We collected 60 uterine leiomyomas from 41 women. Tumor size ranged from 1 to
12cm. Patients' ages ranged from 25 to 55 years with an average of 38.4 years. Of
the 60 tumors, 40 (66.67%) displayed MED12 mutation. Among the 41 patients, 14
patients had multiple leiomyomas and we analyzed those multiple leiomyomas. Three
of them had the same mutations. Five of them, each leiomyoma had a different
mutation. Two of them did not have mutation. Four of them had both mutation
positive and mutation-negative leiomyomas. In conclusion, we confirmed the high
frequency of the MED12 mutation in uterine leiomyomas of South Korean patients.
We also identified various MED12 mutation status in patients with multiple
leiomyomas. This suggests that in a given patient, different tumors may have
arisen from different cell origins and therefore it is supposed that occurrence
of multiple leiomyoma in a single patient may not be caused by intrauterine
metastasis or dissemination.
PMID- 29333097
TI - Preliminary Study of MR and Fluorescence Dual-mode Imaging: Combined Macrophage
Targeted and Superparamagnetic Polymeric Micelles.
AB - Purpose: To establish small-sized superparamagnetic polymeric micelles for
magnetic resonance and fluorescent dual-modal imaging, we investigated the
feasibility of MR imaging (MRI) and macrophage-targeted in vitro. Methods: A new
class of superparamagnetic iron oxide nanoparticles (SPIONs) and Nile red-co
loaded mPEG-Lys3-CA4-NR/SPION polymeric micelles was synthesized to label
Raw264.7 cells. The physical characteristics of the polymeric micelles were
assessed, the T2 relaxation rate was calculated, and the effect of labeling on
the cell viability and cytotoxicity was also determined in vitro. In addition,
further evaluation of the application potential of the micelles was conducted via
in vitro MRI. Results: The diameter of the mPEG-Lys3-CA4-NR/SPION polymeric
micelles was 33.8 +/- 5.8 nm on average. Compared with the hydrophilic SPIO, mPEG
Lys3-CA4-NR/SPION micelles increased transversely (r2), leading to a notably high
r2 from 1.908 ug/mL-1S-1 up to 5.032 ug/mL-1S-1, making the mPEG-Lys3-CA4
NR/SPION micelles a highly sensitive MRI T2 contrast agent, as further
demonstrated by in vitro MRI. The results of Confocal Laser Scanning Microscopy
(CLSM) and Prussian blue staining of Raw264.7 after incubation with micelle
containing medium indicated that the cellular uptake efficiency is high.
Conclusion: We successfully synthesized dual-modal MR and fluorescence imaging
mPEG-Lys3-CA4-NR/SPION polymeric micelles with an ultra-small size and high MRI
sensitivity, which were effectively and quickly uptaken into Raw 264.7 cells.
mPEG-Lys3-CA4-NR/SPION polymeric micelles might become a new MR lymphography
contrast agent, with high effectiveness and high MRI sensitivity.
PMID- 29333098
TI - MiR-22-3p Regulates Cell Proliferation and Inhibits Cell Apoptosis through
Targeting the eIF4EBP3 Gene in Human Cervical Squamous Carcinoma Cells.
AB - Background: MicroRNAs (miRNAs) are non-coding small RNAs that function as
negative regulators of gene expression and are involved in tumour biology. The
eIF4E-binding proteins (eIF4EBPs) play essential roles in preventing translation
initiation and inhibiting protein synthesis at a global or message-specific level
in a variety of tumours. Methods: According to comparative miRNA profiles of
clinical cervical cancer and non-cancerous cervical tissue specimens, several
miRNAs were aberrantly expressed in the cervical cancer samples. C33a and SiHa
cell proliferation and apoptosis were detected using methyl thiazolyl tetrazolium
(MTT) and flow cytometry assays, respectively. Results: Among the aberrantly
expressed miRNAs, miR-22-3p was significantly differentially expressed in
cervical cancer tissues and was highly associated with cervical cancer cell
growth regulation. In addition, bioinformatic predictions and experimental
validation were used to identify whether eIF4E-binding protein 3 (eIF4EBP3) was a
direct target of miR-22-3p; eIF4EBP3 protein levels were generally low in the
cervical cancer tissues. Furthermore, functional studies revealed that either a
miR-22-3p inhibitor or eIF4EBP3 overexpression could induce apoptosis in cervical
cancer cells in vitro. Importantly, we found that eIF4EBP3 accumulation could
significantly attenuate cervical cancer cell proliferation triggered by a miR-22
3p mimic as well as enhance apoptosis in cervical cancer cells. Conclusion: Taken
together, our data provide primary proof that miR-22-3p can induce cervical
cancer cell growth at least in part by up-regulating its expression to decrease
eIF4EBP3 expression levels; miR-22-3p thus holds promise as a prognostic
biomarker and potential therapeutic target for treating cervical cancer.
PMID- 29333099
TI - Pulsed Radiofrequency Applied to the Sciatic Nerve Improves Neuropathic Pain by
Down-regulating The Expression of Calcitonin Gene-related Peptide in the Dorsal
Root Ganglion.
AB - Background: Clinical studies have shown that applying pulsed radiofrequency (PRF)
to the neural stem could relieve neuropathic pain (NP), albeit through an unclear
analgesic mechanism. And animal experiments have indicated that calcitonin gene
related peptide (CGRP) expressed in the dorsal root ganglion (DRG) is involved in
generating and maintaining NP. In this case, it is uncertain whether PRF plays an
analgesic role by affecting CGRP expression in DRG. Methods: Rats were randomly
divided into four groups: Groups A, B, C, and D. In Groups C and D, the right
sciatic nerve was ligated to establish the CCI model, while in Groups A and B,
the sciatic nerve was isolated without ligation. After 14 days, the right sciatic
nerve in Groups B and D re-exposed and was treated with PRF on the ligation site.
Thermal withdrawal latency (TWL) and hindpaw withdrawal threshold (HWT) were
measured before PRF treatment (Day 0) as well as after 2, 4, 8, and 14 days of
treatment. At the same time points of the behavioral tests, the right L4-L6 DRG
was sampled and analyzed for CGRP expression using RT-qPCR and an enzyme-linked
immunosorbent assay (ELISA). Results: Fourteen days after sciatic nerve ligation,
rats in Groups C and D had a shortened TWL (P<0.001) and a reduced HWT (P<0.001)
compared to those in Groups A and B. After PRF treatment, the TWL of the rats in
Group D gradually extended with HWT increasing progressively. Prior to PRF
treatment (Day 0), CGRP mRNA expressions in the L4-L6 DRG of Groups C and D
increased significantly (P<0.001) and were 2.7 and 2.6 times that of Group A
respectively. ELISA results showed that the CGRP content of Groups C and D
significantly increased in comparison with that of Groups A and B (P<0.01). After
PRF treatment, the mRNA expression in the DRG of Group D gradually decreased and
the mRNA expression was 1.7 times that of Group A on the 4th day(P> 0.05). On the
8th and 14th days, the mRNA levels in Group D were restored to those of Groups A
and B. Meanwhile, the CGRP content of Group D gradually dropped over time, from
76.4 pg/mg (Day 0) to 57.5 pg/mg (Day 14). Conclusions: In this study, we found
that, after sciatic nerve ligation, rats exhibited apparent hyperalgesia and
allodynia, and CGRP mRNA and CGRP contents in the L4-L6 DRG increased
significantly. Through lowering CGRP expression in the DRG, PRF treatment might
relieve the pain behaviors of NP.
PMID- 29333100
TI - Assessment of the Temporomandibular Joint Function in Young Adults without
Complaints from the Masticatory System.
AB - Objective of the study was to evaluate the clinical status of the masticatory
system in young adults with full permanent dentition and no stomatognathic system
complaints. The study involved 186 randomly selected people with full dental
arches with normal occlusal conditions corresponding to Angle's Class I aged 18 -
21 years with an average age of 19 years. Subjects were clinically examined and
temporomandibular joint (TMJ) vibrations were recorded during open-wide and close
movements using BioJVA. Then, patients were categorized into groups according to
Piper's classification system. The TMJs of the subjects were categorized
according to the values of the vibration energy and the Piper protocol. This
detected 33.4% of the joints with loosened ligaments, subluxation in 8.28%,
initial signs of disc dysfunction in 5.08% and disc displacement without locking
in 1.6 %. Median frequency differed significantly (p < 0.05) between the group of
subjects with initial signs of TMJ dysfunction and other groups. Peak Frequency
differed significantly (p < 0.05) between the healthy joints and those with TMJ
subluxation. In this group of young healthy people, the majority of study joints
generated small vibrations. However, a subset of people manifested higher
vibrations that may indicate an early stage of TMJ dysfunction. Median Frequency
was an important parameter for detecting initial symptoms of TMJ dysfunction.
Peak Frequency was an important characteristic parameter for detecting TMJ
subluxation.
PMID- 29333101
TI - Variations in the AURKA Gene: Biomarkers for the Development and Progression of
Hepatocellular Carcinoma.
AB - Hepatocellular carcinoma (HCC) is a liver malignancy and a major cause of cancer
mortality worldwide. AURKA (aurora kinase A) is a mitotic serine/threonine kinase
that functions as an oncogene and plays a critical role in hepatocarcinogenesis.
We report on the association between 4 single nucleotide polymorphisms (SNPs) of
the AURKA gene (rs1047972, rs2273535, rs2064836, and rs6024836) and HCC
susceptibility as well as clinical outcomes in 312 patients with HCC and in 624
cancer-free controls. We found that carriers of the TT allele of the variant
rs1047972 were at greater risk of HCC compared with wild-type (CC) carriers.
Moreover, carriers of at least one A allele in rs2273535 were less likely to
progress to stage III/IV disease, develop large tumors or be classified into
Child-Pugh class B or C. Individuals with at least one G allele at AURKA SNP
rs2064863 were at lower risk of developing large tumors or progressing to Child
Pugh grade B or C. Our results indicate that genetic variations in the AURKA gene
may serve as an important predictor of early-stage HCC and be a reliable
biomarker for the development of HCC.
PMID- 29333102
TI - An Amino Acids Mixture Attenuates Glycemic Impairment but not Affects Adiposity
Development in Rats Fed with AGEs-containing Diet.
AB - Background: Unhealthy western dietary patterns lead to over-consumption of fat
and advanced glycation end-products (AGEs), and these account for the
developments of obesity, diabetes, and related metabolic disorders. Certain amino
acids (AAs) have been recently demonstrated to improve glycemia and reduce
adiposity. Therefore, our primary aims were to examine whether feeding an
isoleucine-enriched AA mixture (4.5% AAs; Ile: 3.0%, Leu: 1.0%, Val: 0.2%, Arg:
0.3% in the drinking water) would affect adiposity development and prevent the
impairments of glycemic control in rats fed with the fat/AGE-containing diet
(FAD). Methods: Twenty-four male Sprague-Dawley rats were assigned into 1)
control diet (CD, N = 8), 2) FAD diet (FAD, N = 8), and 3) FAD diet plus AA
(FAD/AA, N = 8). After 9-weeks intervention, the glycemic control capacity
(glucose level, ITT, and HbA1c levels), body composition, and spontaneous
locomotor activity (SLA) were evaluated, and the fasting blood samples were
collected for analyzing metabolic related hormones (insulin, leptin, adiponectin,
and corticosterone). The adipose tissues were also surgically collected and
weighed. Results: FAD rats showed significant increases in weight gain, body fat
%, blood glucose, HbA1c, leptin, and area under the curve of glucose during
insulin tolerance test (ITT-glucose-AUC) in compared with the CD rats. However,
the fasting levels of blood glucose, HbA1c, leptin, and ITT-glucose-AUC did not
differ between CD and FAD/AA rats. FAD/AA rats also showed a greater increase in
serum testosterone. Conclusion: The amino acid mixture consisting of Ile, Leu,
Val, and Arg showed clear protective benefits on preventing the FAD-induced
obesity and impaired glycemic control.
PMID- 29333103
TI - Interleukin-35 Level Is Elevated in Patients with Chronic Hepatitis B Virus
Infection.
AB - Backgrounds: As one of the major public health problems, the hepatitis B virus
(HBV) infection would activate the immune system. The outcome of HBV infection
was affect significantly by the interactions between HBV and host immune
response. Interleukins play important role in anti-viral immunity. Here we
investigated the role of interleukin-35 (IL-35) in chronic HBV infection
patients. Methods/Results: Serum IL-35 in 72 chronic hepatitis B virus infection
patients and 41 healthy control subjects were analyzed by ELISA assay. The mRNA
level of IL-35 in PBMCs was determined by RT-qPCR. In this study, we found that
both protein and mRNA levels of IL-35 were significantly decreased in chronic HBV
patients compared to the healthy controls. Furthermore, the statistical analysis
found that serum IL-35 was significantly associated with HBV DNA (P =0.0158), ALT
(P =0.0003), AST (P =0.0216), TB (P =0.0270) and AFP (P =0.0369). Importantly,
correlation analysis also found that serum IL-35 level was negatively correlated
with HBV DNA copies, ALT, AST, TB and AFP. Meanwhile, IL-35 treatment inhibited
the level of HBV DNA, HBsAg and HBeAg in HepAD38 cells. Conclusion: Our study
identified that IL-35 may be a novel marker associated with HBV infection and
hepatocytes injury. These data suggested the potential use of IL-35 in the HBV
treatment.
PMID- 29333104
TI - What Did You Expect?: The Interaction Between Cigarette and Blunt vs. Non-Blunt
Marijuana Use among African American Young Adults.
AB - Background: Marijuana and tobacco co-use is highly prevalent among African
American young adults. In an effort to inform prevention and treatment
interventions, the current study examined the expectancies around the co-use of
marijuana and cigarettes among African American young adults. Methods: An
anonymous online survey recruited African American adults (N = 111) age 18 to 29
who reported past-month marijuana and cigarette co-use. Participants completed
the 14-item Nicotine and Marijuana Interaction Expectancy (NAMIE) Questionnaire,
with three scales: (1) marijuana use increases tobacco use and urges, (2) tobacco
use increases marijuana use and urges and (3) smoking to cope with marijuana
urges. Participants also answered questions about marijuana and tobacco
initiation and use. Analyses were conducted separately for blunt co-users (i.e.,
blunt and cigarette use) and non-blunt co-users (i.e., non-blunt marijuana and
cigarette use). Results: A majority of co-users (66%) used blunts as a form of co
use. Non-blunt co-users had higher expectancy scores on NAMIE scales 2 and 3 than
blunt co-users. However, only blunt co-users showed a positive association
between severity of marijuana use and NAMIE scales 2 (p <.01) and 3 (p <.01).
Conclusions: Findings provide further evidence for the use of the NAMIE and
suggest a need to assess and address expectations regarding marijuana and tobacco
co-use in prevention and treatment interventions, especially among young African
American adults who co-use blunts and cigarettes.
PMID- 29333106
TI - Which Point-of-Care Tests Would Be Most Beneficial to Add to Clinical Practice?:
Findings From a Survey of 3 Family Medicine Clinics in the United States.
AB - Background: Point-of-care tests (POCTs) are increasingly used in family medicine
to facilitate screening, diagnosis, monitoring, treatment, and referral decisions
for a variety of conditions. Point-of-care tests that clinicians believe might be
beneficial to add to clinical practice and the conditions for which they would be
most useful in family medicine remain poorly understood in the United States.
Methods: Forty-two clinicians at 3 family medicine residency clinics completed a
brief survey asking which POCTs they believed would be beneficial to add to their
clinical practice and the conditions POCTs would be most useful for. We
calculated frequencies of reported POCTs and conditions using descriptive
statistics. Results: Clinicians identified 34 POCTs that would be beneficial to
add to family medicine, of which hemoglobin A1c, chemistry panels, and human
immunodeficiency virus and gonococcal and/or chlamydia were most frequently
reported and anticipated would be used weekly. Clinicians reported 30 conditions
for which they considered POCTs would be useful. Diabetes mellitus, sexually
transmitted infections, and respiratory tract infections were the most often
reported and were identified as benefiting diagnosis, monitoring, and treatment
decisions. Conclusions: Clinicians identified a number of POCTs they viewed as
being beneficial to add to their routine clinical practice, mostly to inform
diagnosis and treatment planning. Some POCTs identified are available in the
United States; thus, understanding barriers to implementation of these POCTs in
primary care settings is necessary to optimize adoption.
PMID- 29333107
TI - Cryptography Standards in Quantum Time: New wine in old wineskin?
PMID- 29333105
TI - Measures and Metrics for Feasibility of Proof-of-Concept Studies With Human
Immunodeficiency Virus Rapid Point-of-Care Technologies: The Evidence and the
Framework.
AB - Objective: Pilot (feasibility) studies form a vast majority of diagnostic studies
with point-of-care technologies but often lack use of clear measures/metrics and
a consistent framework for reporting and evaluation. To fill this gap, we
systematically reviewed data to (a) catalog feasibility measures/metrics and (b)
propose a framework. Methods: For the period January 2000 to March 2014, 2
reviewers searched 4 databases (MEDLINE, EMBASE, CINAHL, Scopus), retrieved 1441
citations, and abstracted data from 81 studies. We observed 2 major categories of
measures, that is, implementation centered and patient centered, and 4
subcategories of measures, that is, feasibility, acceptability, preference, and
patient experience. We defined and delineated metrics and measures for a
feasibility framework. We documented impact measures for a comparison. Findings:
We observed heterogeneity in reporting of metrics as well as misclassification
and misuse of metrics within measures. Although we observed poorly defined
measures and metrics for feasibility, preference, and patient experience, in
contrast, acceptability measure was the best defined. For example, within
feasibility, metrics such as consent, completion, new infection, linkage rates,
and turnaround times were misclassified and reported. Similarly, patient
experience was variously reported as test convenience, comfort, pain, and/or
satisfaction. In contrast, within impact measures, all the metrics were well
documented, thus serving as a good baseline comparator. With our framework, we
classified, delineated, and defined quantitative measures and metrics for
feasibility. Conclusions: Our framework, with its defined measures/metrics, could
reduce misclassification and improve the overall quality of reporting for
monitoring and evaluation of rapid point-of-care technology strategies and their
context-driven optimization.
PMID- 29333108
TI - Bipolar Disorder in Primary Care: Integrated Care Experiences.
AB - Primary care clinics are increasingly implementing collaborative care models to
care for patients with psychiatric illnesses in primary care. The evidence base
for the effectiveness of collaborative care has largely been derived from the
care of patients with depression or anxiety disorders, although psychiatrists
working in primary care may encounter patients with illnesses other than
depression or anxiety disorder, notably bipolar disorder. Patients with bipolar
disorder report having received treatment in primary care in equal proportions as
those in specialty care settings over the past 12 months, although quality of
care is lower in primary care than in specialty care settings. For patients
already presenting to primary care, collaborative care is one population-based
care model that may increase the proportion of individuals with bipolar disorder
who are exposed to high-quality psychiatric care, such as appropriate medication
treatment and laboratory monitoring. The primary care setting may even present
unexpected strengths in caring for patients with bipolar disorder. Solutions to
barriers to expanding the scope of collaborative care to include patients with
bipolar disorder may apply to the care of patients with other complex disorders
in the primary care setting.
PMID- 29333109
TI - Ultrasonographic Findings of Renal Cell Carcinomas Associated with Xp11.2
Translocation/TFE3 Gene Fusion.
AB - Objective: This study was to investigate the features of renal carcinomas
associated with Xp11.2 translocations/TFE3 gene fusions (Xp11.2-RCC) on
conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS). Methods: US
and CEUS features of twenty-two cases with histopathologically proven Xp11.2-RCC
were retrospectively reviewed. Results: 22 patients (11 males, 11 females) were
included in this study, with a mean age of 28.3 +/- 20.4 years. Eight tumors
(36.3%, 8/22) were in left kidney, and 14 tumors (63.7%, 14/22) were in right
kidney. All tumors (100%, 22/22) were mixed echogenicity type. 13 tumors (59.1%,
13/22) presented small dotted calcifications. The boundary of 14 tumors (63.6%,
14/22) was sharp and the other 8 tumors' (36.4%, 8/22) boundary was blurry. By
CEUS, in early phase, the solid element of all tumors showed obvious enhancement.
In delayed phase, 13 tumors showed hypoenhancement, seven tumors showed
isoenhancement, and 2 tumors showed hyperenhancement. There were irregular
nonenhancement areas in all tumors inside. Conclusions: By US and CEUS, when
children and adolescents were found to have hyperechoic mixed tumor in kidney
with sharp margin and calcification, and the tumors showed obvious enhancement
and hypoenhancement with irregular nonenhancement areas in the tumor in early
phase and delayed phase, respectively, Xp11.2-RCC should be suspected.
PMID- 29333110
TI - F-18 FP-CIT PET in Multiple System Atrophy of the Cerebellar Type: Additional
Role in Treatment.
AB - We evaluated the difference in the status of dopamine transporters (DATs)
depending on Parkinsonism, cerebellar, and autonomic features using F-18 FP-CIT
positron emission tomography (PET) in multiple system atrophy with cerebellar
ataxia (MSA-C). We also assessed whether the DAT PET could be useful in the
management of MSA-C. Forty-nine patients who were clinically diagnosed as
possible to probable MSA-C were included. Based on the F-18 FP-CIT PET results,
patients were classified into normal (n = 25) and abnormal (n = 24) scan groups.
There were statistically significant differences in rigidity, bradykinesia,
postural instability, asymmetry, and specific uptake ratio (SUR) between the two
groups but no significant differences in tremor and cerebellar/autonomic
symptoms. Dopaminergic medications were administered to 22 patients. All seven
patients with normal scans showed no change, while 10 of the 15 patients with
abnormal scans showed clinical improvement. There was a trend of a negative
correlation between levodopa equivalent dose and SUR, but it was not
statistically significant. DAT imaging, such as F-18 FP-CIT PET, may be useful in
predicting the response to dopaminergic medication regardless of
cerebellar/autonomic symptoms in MSA-C. In addition to being used for the
diagnosis of the disease, it may be used as a treatment decision index.
PMID- 29333112
TI - Integrating Occupational Therapy Specific Assessments in Practice: Exploring
Practitioner Experiences.
AB - Background: Occupational therapists sometimes find it challenging to integrate
client-centered and occupational therapy specific assessments in practice. The
aim of this study was to explore the use of occupational therapy specific
assessments such as the Assessment of Motor and Process Skills (AMPS) among
occupational therapists in Sweden and Japan. Methods: Interviews and qualitative
thematic analyses were utilized. Findings: Four themes are reported: (1) use it
or lose it, (2) simply no space until after hours, (3) biggest barriers can be
colleagues, and (4) being more specific: communication. Conclusion: In keeping
with previous studies, occupational therapists often find it challenging to
implement client-centered and occupation-based assessment tools into practice.
However, more work is needed to understand how best practices can be incorporated
into a changing occupational therapy daily practice.
PMID- 29333113
TI - Grating Oriented Line-Wise Filtration (GOLF) for Dual-Energy X-ray CT.
AB - In medical X-ray Computed Tomography (CT), the use of two distinct X-ray source
spectra (energies) allows dose-reduction and material discrimination relative to
that achieved with only one source spectrum. Existing dual-energy CT methods
include source kVp-switching, double-layer detection, dual-source gantry, and two
pass scanning. Each method suffers either from strong spectral correlation or
patient-motion artifacts. To simultaneously address these problems, we propose to
improve CT data acquisition with the Grating Oriented Line-wise Filtration (GOLF)
method, a novel X-ray filter that is placed between the source and patient. GOLF
uses a combination of absorption and filtering gratings that are moved relative
to each other and in synchronization with the X-ray tube kVp-switching process
and/or the detector view-sampling process. Simulation results show that GOLF can
improve the spectral performance of kVp-switching to match that of dual-source CT
while avoiding patient motion artifacts and dual imaging chains. Although
significant flux is absorbed by this pre-patient filter, the proposed GOLF method
is a novel path for cost-effectively extracting dual-energy or multi-energy data
and reducing radiation dose with or without kVp switching.
PMID- 29333111
TI - Diet, Gut Microbiota, and Colorectal Cancer Prevention: A Review of Potential
Mechanisms and Promising Targets for Future Research.
AB - Diet plays an important role in the development of colorectal cancer. Emerging
data have implicated the gut microbiota in colorectal cancer. Diet is a major
determinant for the gut microbial structure and function. Therefore, it has been
hypothesized that alterations in gut microbes and their metabolites may
contribute to the influence of diet on the development of colorectal cancer. We
review several major dietary factors that have been linked to gut microbiota and
colorectal cancer, including major dietary patterns, fiber, red meat and sulfur,
and obesity. Most of the epidemiologic evidence derives from cross-sectional or
short-term, highly controlled feeding studies that are limited in size.
Therefore, high-quality large-scale prospective studies with dietary data
collected over the life course and comprehensive gut microbial composition and
function assessed well prior to neoplastic occurrence are critically needed to
identify microbiome-based interventions that may complement or optimize current
diet-based strategies for colorectal cancer prevention and management.
PMID- 29333114
TI - Carcinogenesis Induced by Low-dose Radiation.
AB - Background: Although the effects of high dose radiation on human cells and
tissues are relatively well defined, there is no consensus regarding the effects
of low and very low radiation doses on the organism. Ionizing radiation has been
shown to induce gene mutations and chromosome aberrations which are known to be
involved in the process of carcinogenesis. The induction of secondary cancers is
a challenging long-term side effect in oncologic patients treated with radiation.
Medical sources of radiation like intensity modulated radiotherapy used in cancer
treatment and computed tomography used in diagnostics, deliver very low doses of
radiation to large volumes of healthy tissue, which might contribute to increased
cancer rates in long surviving patients and in the general population. Research
shows that because of the phenomena characteristic for low dose radiation the
risk of cancer induction from exposure of healthy tissues to low dose radiation
can be greater than the risk calculated from linear no-threshold model.
Epidemiological data collected from radiation workers and atomic bomb survivors
confirms that exposure to low dose radiation can contribute to increased cancer
risk and also that the risk might correlate with the age at exposure.
Conclusions: Understanding the molecular mechanisms of response to low dose
radiation is crucial for the proper evaluation of risks and benefits that stem
from these exposures and should be considered in the radiotherapy treatment
planning and in determining the allowed occupational exposures.
PMID- 29333115
TI - Clinical Significance of Fluorine-18-fluorodeoxyglucose Positron Emission
Tomography/computed Tomography in the Follow-up of Colorectal Cancer: Searching
off Approaches Increasing Specificity for Detection of Recurrence.
AB - Background: Nearly 40% of colorectal cancer (CRC) recurs within 2 years after
resection of primary tumor. Imaging with fluorine-18-fluorodeoxyglucose (l8F-FDG)
positron emission tomography/computed tomography (PET/CT) is the most recent
modality and often applied for the evaluation of metastatic spread during the
follow-up period. Our goal was to study the diagnostic importance of 18F-FDG
PET/CT data of maximum standardized uptake value (SUVmax), total lesion
glycolysis (TLG) and the difference of SUVmax on dual-time imaging in CRC.
Patients and methods: We examined the SUVmax value of lesions on control or
restaging 18F-FDG-PET/CT of 53 CRC patients. All lesions with increased SUVmax
values were confirmed by colonoscopy or histopathology. We compared PET/CT
results with conventional imaging modalities (CT, MRI) and tumor markers
(carbohydrate antigen 19-9 [Ca 19-9], carcinoembryonic antigen [CEA]). Results:
Mean SUVmax was 6.9 +/- 5.6 in benign group, 12.7 +/- 6.1 in malignant group.
Mean TLG values of malignant group and benign group were 401 and 148,
respectively. 18F-FDG-PET/CT was truely positive in 48% of patients with normal
Ca 19-9 or CEA levels and truely negative in 10% of cases with elevated Ca 19-9
or CEA. CT or MRI detected suspicious malignancy in 32% of the patients and 18F
FDG-PET/CT was truely negative in 35% of these cases. We found the most important
and striking statistical difference of TLG value between the groups with benign
and recurrent disease. Conclusions: Although SUVmax is a strong metabolic
parameter (p = 0.008), TLG seems to be the best predictor in recurrence of CRC (p
= 0.001); both are increasing the specificity of 18F-FDG-PET/CT.
PMID- 29333116
TI - Is there a Role for Contrast-enhanced Ultrasound in the Detection and Biopsy of
MRI Only Visible Breast Lesions?
AB - Background: This study aimed to evaluate the feasibility of contrast-enhanced
ultrasound (CEUS) and CEUS-guided interventions in the diagnostics of MRI visible
targeted US occult breast lesions. Patients and methods: This retrospective study
examined 10 females with 10 occult, MRI only detected breast lesions between July
2014 and April 2017. Targeted second look US followed by CEUS with 2.4 ml of
SonoVue(r) were performed for all of the lesions. After positive CEUS
localization the same dose was repeated for confirmation and CEUS-guided
interventions were performed. Results: MRI revealed 8 mass lesions with a mean
size of 9 mm (range 5-16 mm) and 2 non-mass enhancing lesions of 10 and 20 mm in
largest diameters. Targeted US revealed no morphological correlate for the
lesions. Five out of 10 lesions (50%) were visible on CEUS. CEUS-guided core
biopsy was performed on 4 lesions and 1 was marked with a clip for later surgical
removal. Histopathological analysis confirmed 4 of them to be malignant. Three
out of 5 nonvisible lesions on CEUS underwent MRI-guided interventions, 1 lesion
was scheduled for follow-up as it was non-amenable for MRI biopsy, and 1 lesion
was biopsied under US-guidance. Three of these nonvisible lesions on CEUS were
confirmed to be malignant. Conclusions: Based on our preliminary results, CEUS is
a feasible tool for detecting many MRI only visible breast lesions, resulting in
a more cost effective and less time-consuming practice. It is a more convenient
alternative than MRI guided biopsy and has the potential to be included in the
diagnostic algorithm which evaluates MRI only visible breast lesions.
PMID- 29333117
TI - Baseline Tumor Lipiodol Uptake after Transarterial Chemoembolization for
Hepatocellular Carcinoma: Identification of a Threshold Value Predicting Tumor
Recurrence.
AB - Background: The aim of the study was to evaluate the association between baseline
Lipiodol uptake in hepatocellular carcinoma (HCC) after transarterial
chemoembolization (TACE) with early tumor recurrence, and to identify a threshold
baseline uptake value predicting tumor response. Patients and methods: A single
institution retrospective database of HCC treated with Lipiodol-TACE was
reviewed. Forty-six tumors in 30 patients treated with a Lipiodol-chemotherapy
emulsion and no additional particle embolization were included. Baseline Lipiodol
uptake was measured as the mean Hounsfield units (HU) on a CT within one week
after TACE. Washout rate was calculated dividing the difference in HU between the
baseline CT and follow-up CT by time (HU/month). Cox proportional hazard models
were used to correlate baseline Lipiodol uptake and other variables with tumor
response. A receiver operating characteristic (ROC) curve was used to identify
the optimal threshold for baseline Lipiodol uptake predicting tumor response.
Results: During the follow-up period (mean 5.6 months), 19 (41.3%) tumors
recurred (mean time to recurrence = 3.6 months). In a multivariate model, low
baseline Lipiodol uptake and higher washout rate were significant predictors of
early tumor recurrence (P = 0.001 and < 0.0001, respectively). On ROC analysis, a
threshold Lipiodol uptake of 270.2 HU was significantly associated with tumor
response (95% sensitivity, 93% specificity). Conclusions: Baseline Lipiodol
uptake and washout rate on follow-up were independent predictors of early tumor
recurrence. A threshold value of baseline Lipiodol uptake > 270.2 HU was highly
sensitive and specific for tumor response. These findings may prove useful for
determining subsequent treatment strategies after Lipiodol TACE.
PMID- 29333118
TI - The Relationship between Chondromalacia Patella, Medial Meniscal Tear and Medial
Periarticular Bursitis in Patients with Osteoarthritis.
AB - Background: This study investigated the presence of bursitis in the medial
compartment of the knee (pes anserine, semimembranosus-tibial collateral
ligament, and medial collateral ligament bursa) in osteoarthritis, chondromalacia
patella and medial meniscal tears. Patients and methods: Radiological findings of
100 patients undergoing magnetic resonance imaging with a preliminary diagnosis
of knee pain were retrospectively evaluated by two radiologists. The first
radiologist assessed all patients in terms of osteoarthritis, chondromalacia
patella and medial meniscal tear. The second radiologist was blinded to these
results and assessed the presence of bursitis in all patients. Results: Mild
osteoarthritis (grade I and II) was determined in 55 patients and severe
osteoarthritis (grade III and IV) in 45 cases. At retropatellar cartilage
evaluation, 25 patients were assessed as normal, while 29 patients were diagnosed
with mild chondromalacia patella (grade I and II) and 46 with severe
chondromalacia patella (grade III and IV). Medial meniscus tear was determined in
51 patients. Severe osteoarthritis and chondromalacia patella were positively
correlated with meniscal tear (p < 0.001 and p = 0.018, respectively).
Significant correlation was observed between medial meniscal tear and bursitis in
the medial compartment (p = 0.038). Presence of medial periarticular bursitis was
positively correlated with severity of osteoarthritis but exhibited no
correlation with chondromalacia patella (p = 0.023 and p = 0.479, respectively).
Evaluation of lateral compartment bursae revealed lateral collateral ligament
bursitis in 2 patients and iliotibial bursitis in 5 patients. Conclusions: We
observed a greater prevalence of bursitis in the medial compartment of the knee
in patients with severe osteoarthritis and medial meniscus tear.
PMID- 29333119
TI - Phytotherapeutics Oridonin and Ponicidin show Additive Effects Combined with
Irradiation in Pancreatic Cancer in Vitro.
AB - Background: Chemoradiation of locally advanced non-metastatic pancreatic cancer
can lead to secondary operability by tumor mass reduction. Here, we analyzed
radiomodulating effects of oridonin and ponicidin in pancreatic cancer in vitro.
Both agents are ent-kaurane diterpenoids, extracted from Isodon rubescens, a
plant that is well known in Traditional Chinese Medicine. Cytotoxic effects have
recently been shown in different tumor entities for both agents. Materials and
methods: Pancreatic cancer cell lines AsPC-1, BxPC-3, Panc-1 and MIA PaCa-2 were
pretreated with oridonin or ponicidin and irradiated with 2 Gy to 6 Gy. Long-term
survival was determined by clonogenic assay. Cell cycle effects and intensity of
gammaH2AX as indicator for DNA double-strand breaks were investigated by flow
cytometry. Western blotting was used to study the DNA double-strand break repair
proteins Ku70, Ku80 and XRCC4. Results: Oridonin and ponicidin lead to a dose
dependent reduction of clonogenic survival and an increase in gammaH2AX. Combined
with irradiation we observed additive effects and a prolonged G2/M-arrest. No
relevant changes in the levels of the DNA double-strand break repair proteins
were detected. Conclusions: Pretreatment with oridonin or ponicidin followed by
irradiation lead to an additional reduction in survival of pancreatic cancer
cells in vitro, presumably explained by an induced prolonged G2/M-arrest. Both
agents seem to induce DNA double-strand breaks but do not interact with the non
homologous end joining (NHEJ) pathway.
PMID- 29333120
TI - Focused Transhepatic Electroporation Mediated by Hypersaline Infusion through the
Portal Vein in Rat Model. Preliminary Results on Differential Conductivity.
AB - Background: Spread hepatic tumours are not suitable for treatment either by
surgery or conventional ablation methods. The aim of this study was to evaluate
feasibility and safety of selectively increasing the healthy hepatic conductivity
by the hypersaline infusion (HI) through the portal vein. We hypothesize this
will allow simultaneous safe treatment of all nodules by irreversible
electroporation (IRE) when applied in a transhepatic fashion. Material and
methods: Sprague Dawley (Group A, n = 10) and Athymic rats with implanted hepatic
tumour (Group B, n = 8) were employed. HI was performed (NaCl 20%, 3.8 mL/Kg) by
trans-splenic puncture. Deionized serum (40 mL/Kg) and furosemide (2 mL/Kg) were
simultaneously infused through the jugular vein to compensate hypernatremia.
Changes in conductivity were monitored in the hepatic and tumour tissue. The
period in which hepatic conductivity was higher than tumour conductivity was
defined as the therapeutic window (TW). Animals were monitored during 1-month
follow-up. The animals were sacrificed and selective samples were used for
histological analysis. Results: The overall survival rate was 82.4% after the HI
protocol. The mean maximum hepatic conductivity after HI was 2.7 and 3.5 times
higher than the baseline value, in group A and B, respectively. The mean maximum
hepatic conductivity after HI was 1.4 times higher than tumour tissue in group B
creating a TW to implement selective IRE. Conclusions: HI through the portal vein
is safe when the hypersaline overload is compensated with deionized serum and it
may provide a TW for focused IRE treatment on tumour nodules.
PMID- 29333121
TI - Minimally Invasive Electrochemotherapy Procedure for Treating Nasal Duct Tumors
in Dogs using a Single Needle Electrode.
AB - Background: Nasal cavity tumors are usually diagnosed late, when they already
have infiltrated adjacent tissues thus requiring very aggressive treatments with
serious side effects. Here we use electrochemotherapy (ECT), a well demonstrated
treatment modality for superficial tumors. Materials and methods: In the case of
deep-seated tumors, the main limitation of ECT is reaching the tumor with an
appropriate electric field. To overcome this limitation we introduce the single
needle electrode (SiNE), a minimally invasive device that can deliver an
appropriate electric field with a simple procedure. Twenty-one canine patients
with spontaneous tumors were selected, eleven were treated using the SiNE with
ECT, and ten with surgery plus adjuvant chemotherapy as a control group. Results:
In the SiNE group, 27% achieved a complete response, 64% had a partial response,
and 9% had a stable disease. This means that 91% of objective responses were
obtained. The mean overall survival was 16.86 months (4-32 months, median 16.5
months), with a survival rate significantly higher (p = 0.0008) when compared
with control group. The only side effect observed was the inflammation of the
treated nasal passage, which was controlled with corticosteroid therapy for one
week. One year after the treatment, 60% of the canine of the SiNE group vs. 10%
of the control group remained alive, and after the 32 months follow-up, the
survival rate were 30% and 0%, respectively. Conclusions: ECT with the SiNE can
be safely used in canine to treat nasal tumors with encouraging results.
PMID- 29333122
TI - Metformin Enhanced in Vitro Radiosensitivity Associates with G2/M Cell Cycle
Arrest and Elevated Adenosine-5'-monophosphate-activated Protein Kinase Levels in
Glioblastoma.
AB - Background: It is hypothesized that metabolism plays a strong role in cancer cell
regulation. We have recently demonstrated improved progression-free survival in
patients with glioblastoma who received metformin as an antidiabetic substance
during chemoradiation. Although metformin is well-established in clinical use the
influence of metformin in glioblastoma is far from being understood especially in
combination with other treatment modalities such as radiation and temozolomide.
Materials and Methods: In this study, we examined the influence of metformin in
combinations with radiation and temozolomide on cell survival (clonogenic
survival), cell cycle (routine flow cytometric analysis, FACScan), and
phosphorylated Adenosine-5'-monophosphate-activated protein kinase (AMPK) (Phopho
AMPKalpha1 - ELISA) levels in glioblastoma cell lines LN18 and LN229. Results:
Metformin and temozolomide enhanced the effectiveness of photon irradiation in
glioblastoma cells. Cell toxicity was more pronounced in O6-methylguanine DNA
methyltransferase (MGMT) promoter non-methylated LN18 cells. Induction of a G2/M
phase cell cycle block through metformin and combined treatments was observed up
to 72 h. These findings were associated with elevated levels of activated AMPK
levels in LN229 cells but not in LN18 cells after irradiation, metformin, and
temozolomide treatment. Conclusions: Radiosensitizing effects of metformin on
glioblastoma cells treated with irradiation and temozolomide in vitro coincided
with G2/M arrest and changes in pAMPK levels.
PMID- 29333123
TI - Evaluation of Deformable Image Registration (DIR) Methods for Dose Accumulation
in Nasopharyngeal Cancer Patients during Radiotherapy.
AB - Introduction: Deformable image registration (DIR) is used to modify structures
according to anatomical changes for observing the dosimetric effect. In this
study, megavoltage computed tomography (MVCT) images were used to generate
cumulative doses for nasopharyngeal cancer (NPC) patients by various DIR methods.
The performance of the multiple DIR methods was analysed, and the impact of dose
accumulation was assessed. Patients and methods: The study consisted of five NPC
patients treated with a helical tomotherapy unit. The weekly MVCT images at the
1st, 6th, 11th, 16th, 21st, 26th, and 31st fractions were used to assess the dose
accumulation by the four DIR methods. The cumulative dose deviations from the
initial treatment plan were analysed, and correlations of these variations with
the anatomic changes and DIR methods were explored. Results: The target dose
received a slightly different result from the initial plan at the end of the
treatment. The organ dose differences increased as the treatment progressed to
6.8% (range: 2.2 to 10.9%), 15.2% (range: -1.7 to 36.3%), and 6.4% (range: -1.6
to 13.2%) for the right parotid, the left parotid, and the spinal cord,
respectively. The mean uncertainty values to estimate the accumulated doses for
all the DIR methods were 0.21 +/- 0.11 Gy (target dose), 1.99 +/- 0.76 Gy (right
parotid), 1.19 +/- 0.24 Gy (left parotid), and 0.41 +/- 0.04 Gy (spinal cord).
Conclusions: Accuracy of the DIR methods affects the estimation of dose
accumulation on both the target dose and the organ dose. The DIR methods provide
an adequate dose estimation technique for observation as a result of inter
fractional anatomic changes and are beneficial for adaptive treatment strategies.
PMID- 29333124
TI - Long Term Results of Radiotherapy in Vulvar Cancer Patients in Slovenia between
1997-2004.
AB - Background: The aim of this retrospective single institution study was to analyse
long term results of vulvar cancer treatment with conventional 2D radiotherapy in
Slovenia between years 1997-2004. Patients and methods: Fifty-six patients,
median age 74.4 years +/- 9.7 years, mainly stage T2 or T3, were included in the
study. All patients were treated with radiotherapy, which was combined with
surgery (group A), used as the primary treatment (group B) or at the time of
relapse (group C). Chemotherapy was added in some patients. Histology, grade,
lymph node status, details of surgery, radiation dose to the primary tumour,
inguinofemoral and pelvic area as well as local control (LC) and survival were
evaluated. Results: Overall survival (OS), disease specific survival (DSS) and LC
rates at 10-years for all patients were as follows: 22.7%, 34.5% and 41.1%,
respectively. The best 10-years results of the treatment were achieved in the
primary operated patients treated with adjuvant radiotherapy +/-chemotherapy (OS
31.9%, DSS 40.6% and LC 47.6%). Positive lymph nodes had a strong influence on
LC. In case of positive nodes LC decreased by 60% (p = 0.03) and survival
decreased by 50% (p = 0.2). There was a trend to a better LC with higher doses >=
54.0 Gy (p = 0.05). Conclusions: The best treatment option for patients with
advanced vulvar cancer is combined treatment with surgery and radiotherapy +/-
chemotherapy, if feasible. Radiotherapy with the dose of >= 54.0 Gy should be
considered to achieve better LC if positive adverse factors are present.
PMID- 29333125
TI - Association between SLC19A1 Gene Polymorphism and High Dose Methotrexate Toxicity
in Childhood Acute Lymphoblastic Leukaemia and Non Hodgkin Malignant Lymphoma:
Introducing a Haplotype based Approach.
AB - Background: We investigated the clinical relevance of SLC 19A1 genetic
variability for high dose methotrexate (HD-MTX) related toxicities in children
and adolescents with acute lymphoblastic leukaemia (ALL) and non Hodgkin
malignant lymphoma (NHML). Patients and methods: Eighty-eight children and
adolescents with ALL/NHML were investigated for the influence of SLC 19A1 single
nucleotide polymorphisms (SNPs) and haplotypes on HD-MTX induced toxicities.
Results: Patients with rs2838958 TT genotype had higher probability for mucositis
development as compared to carriers of at least one rs2838958 C allele (OR 0.226
(0.071-0.725), p < 0.009). Haplotype TGTTCCG (H4) statistically significantly
reduced the risk for the occurrence of adverse events during treatment with HD
MTX (OR 0.143 (0.023-0.852), p = 0.030). Conclusions: SLC 19A1 SNP and haplotype
analysis could provide additional information in a personalized HD-MTX therapy
for children with ALL/NHML in order to achieve better treatment outcome. However
further studies are needed to validate the results.
PMID- 29333126
TI - Impact on Radiation Dose and Volume V57 Gy of the Brain on Recurrence and
Survival of Patients with Glioblastoma Multiformae.
AB - Background: The aim of the study was to analyze impact of irradiated brain volume
V57 Gy (volume receiving 57 Gy and more) on time to progression and survival of
patients with glioblastoma. Patients and methods: Dosimetric analysis of
treatment plan data has been performed on 70 patients with glioblastoma, treated
with postoperative radiochemotherapy with temozolomide, followed by adjuvant
temozolomide. Patients were treated with 2 different methods of definition of
treatment volumes and prescription of radiation dose. First group of patients has
been treated with one treatment volume receiving 60 Gy in 2 Gy daily fraction (31
patients) and second group of the patients has been treated with "cone-down"
technique, which consisted of two phases of treatment: the first phase of 46 Gy
in 2 Gy fraction followed by "cone-down" boost of 14 Gy in 2 Gy fraction (39
patients). Quantification of V57 Gy and ratio brain volume/V57Gy has been done.
Average values of both parameters have been taken as a threshold value and
patients have been split into 2 groups for each parameter (values smaller/ lager
than threshold value). Results: Mean value for V57 Gy was 593.39 cm3 (range
166.94 to 968.60 cm3), mean value of brain volume has was 1332.86 cm3 (range
1047.00 to 1671.90 cm3) and mean value of brain-to-V57Gy ratio was 2.46 (range
1.42 to 7.67). There was no significant difference between two groups for both
V57 Gy and ratio between brain volume and V57 Gy. Conclusions: Irradiated volume
with dose 57 Gy or more (V57 Gy) and ration between whole brain volume and 57 Gy
had no impact on time to progression and survival of patients with glioblastoma.
PMID- 29333127
TI - Quality Assurance Procedures based on Dosimetric, Gamma Analysis as a Fast
Reliable Tool for Commissioning Brachytherapy Treatment Planning Systems.
AB - Background: Fast and easily repeatable methods for commissioning procedures for
brachytherapy (BT) treatment planning systems (TPS) are needed. Radiochromic film
dosimetry with gamma analysis is widely used in external beam quality assurance
(QA) procedures and planar film dosimetry is also increasingly used for
verification of the dose distribution in BT applications. Using the gamma
analysis method for comparing calculated and measured dose data could be used for
commissioning procedures of the newly developed TG-186 and MBDCA calculation
algorithms. The aim of this study was dosimetric verification of the calculation
algorithm used in TPS when the CT/MRI ring applicator is used. Materials and
methods: Ring applicators with 26 and 30 mm diameters and a 60 mm intra-uterine
tube with 60 degrees angle were used for verification. Gafchromic(r) EBT films
were used as dosimetric media. Dose grids, corresponding to each plane
(dosimetric film location), were exported from the TPS as a raw data.
Gafchromic(r) films were digitized after irradiation. gamma analysis of the data
were performed using the OMNI Pro I'mRT(r) system, as recommended by the AAPM TG
119 rapport criterion for gamma analysis of 3%, 3 mm and a level of 95%. Results:
For the 26 mm and 30 mm rings, the average gamma ranged, respectively, from 0.1
to 0.44 and from 0.1 to 0.27. In both cases, 99% of the measured points
corresponded with the calculated data. Conclusions: This analysis showed
excellent agreement between the dose distribution calculated with the TPS and the
doses measured by Gafchromic films. This finding confirms the viability of using
film dosimetry in BT.
PMID- 29333128
TI - In vitro transfection of anti-tumor miR-101 induces BIM, a pro-apoptotic protein,
expression in acute myeloid leukemia (AML).
AB - Acute myeloid leukemia (AML) frequently relapses after initial treatment, though
it is possible that drug resistance occurs. Hence, it seems necessary to develop
novel therapies such as gene therapy specifically via miRNA transfection.
MicroRNA-101 has been considered as a tumor suppressor in different types of
cancer. It is demonstrated that exogenous miR-101 transfection is associated with
decreased viability in AML in this paper. Besides, the increase of pro-apoptotic
protein BIM expression in both mRNA and protein level has been illustrated. The
recent findings provide an insight into the novel function of miR-101 in AML by
activating BIM as an important mediator in intrinsic apoptosis pathways.
Generally, miR-101 has been considered as a therapeutic target in our data and
might have a valuable role in AML.
PMID- 29333129
TI - The predictive value of pre- and post-induction chemotherapy plasma EBV DNA level
and tumor volume for the radiosensitivity of locally advanced nasopharyngeal
carcinoma.
AB - This study was dedicated to investigate the predictive value of pre- and post
induction chemotherapy plasma EBV (Epstein-Barr Virus) DNA level and tumor volume
for the radiosensitivity of locally advanced NPC. 129 previously untreated
locally advanced NPC patients were enrolled. Plasma EBV-DNA copy number and tumor
volume was detected before and after induction chemotherapy. The tumor volume was
also measured after radiotherapy. Among 129 patients, 98 were positive for EBV
DNA. The residual gross target volume of the primary tumor (GTVnx) and GTVnd
after radiotherapy was positively correlated with post-induction chemotherapy EBV
copy number (rho=0.357, P<0.001; rho=0.356, P<0.001, respectively). Univariate
logistic regression analyses showed that the AUC of ROC curves of post-induction
chemotherapy tumor volume, tumor regression rate before and after induction
chemotherapy, post-induction EBV copy number, EBV decrease rate for predicting no
residual nasopharyngeal tumor were 0.859, 0.782, 0.678 and 0.657, respectively.
Multivariate logistic analyses showed that T stage, post-induction chemotherapy
EBV copy number and tumor volume were independent predictors for no residual
nasopharyngeal tumor after radiotherapy. The changes in plasma EBV DNA and tumor
volume during treatment could be used to predict the sensitivity of locally
advanced NPC patients in response to intensity-modulated radiation therapy
(IMRT).
PMID- 29333130
TI - An in silico approach in predicting the possible mechanism involving restoration
of wild-type p53 functions by small molecular weight compounds in tumor cells
expressing R273H mutant p53.
AB - R273H mutant p53 is a DNA-contact mutant that renders p53 dysfunctional due to a
single substitution of Arg273 for His273. Rescuing R273 mutant p53 implies that a
competent molecule would have to bind to the site of DNA-contact hot spots to
complement the loss of contact with the DNA-binding domain. Here, curcumin,
flavokawain B, and alpinetin were docked against the crystal structure of R273H
mutant p53 in silico. Consequently, all the compounds bind to the cavity of R273H
mutant p53 with a dissociation constant estimated to have 36.57, 70.77, and 75.11
uM for curcumin, flavokawain B, and alpinetin, respectively. Subsequently, each
molecule was able to bind to the R273H mutant p53 by interacting with the DNA
contact hot spot Arg248 and mutant R273H, thereby compensating for the loss of
direct contact with the DNA-binding domain. Furthermore, all the molecules were
able to induce a direct contact with the consensus site of the DNA binding
domain, thus maintaining DNA-contact residues with the DNA. The present findings
offer preliminary indirect supporting evidence that small molecular weight
compounds may certainly rescue DNA-contact mutant p53, which may lay a foundation
for designing a competent and effective molecule capable of rescuing mutant p53
in tumor cells expressing R273H mutant p53.
PMID- 29333131
TI - miR-494 protects pancreatic beta-cell function by targeting PTEN in gestational
diabetes mellitus.
AB - Gestational diabetes mellitus (GDM) is one of the most common pregnancy
complications characterized by insulin resistance and pancreatic beta-cell
dysfunction. Increasing evidence suggests that microRNAs (miRNAs) play key roles
in the diverse types of diabetes, including GDM. However, the underlying
mechanisms remain largely unknown. The purpose of this study is to investigate
the role of microRNAs in GDM. The microarray data of dysregulated miRNAs in blood
and placenta was retrieved in the GEO dataset under the accession number
GSE19649. Quantitative reverse transcription PCR (qRT-PCR) was performed to
analyze the expression levels of miR-494 in peripheral blood from twenty pairs of
gestational diabetes (GDM) women and healthy women. Then, we investigated the
effects of miR-494 on the insulin secretion of pancreatic beta-cells. Moreover,
the role of this miR-494 in regulating the proliferation and apoptosis of
pancreatic beta-cells were determined by MTT assay and flow cytometry,
respectively in INS1 cells transfected with a miR-494 mimic or inhibitor. In
addition, the direct target of miR-494 was confirmed using 3' untranslated region
(UTR) luciferase reporter assay. Our data demonstrated that the miR-494 level was
significantly decreased in the blood of GDM patients, and the low level was
associated with a high concentration of blood glucose. Furthermore,
overexpression of miR-494 improved pancreatic beta-cell dysfunction by enhancing
insulin secretion and total insulin content, inducing cell proliferation, and
inhibiting cell apoptosis, whereas miR-494 knockdown exhibited decreased insulin
secretion and proliferation, as well as stimulated apoptosis. In addition,
phosphatase and tensin homolog (PTEN) which has been shown to play a pivotal role
in apoptosis, was proved to be a direct target of miR-494 in pancreatic beta
cells. More importantly, siRNA-induced downregulation of PTEN reversed the
effects of miR-494 knockdown on insulin secretion, cell proliferation, and
apoptosis of pancreatic beta-cells.
PMID- 29333132
TI - Detection of aflatoxin-producing fungi isolated from Nile tilapia and fish feed.
AB - Contamination of fish by fungi and their mycotoxins poses major health concerns
to human and animals. Therefore, our study was aimed to investigate Aspergillus
flavus (A. flavus) infections and the levels of aflatoxins in Nile tilapia,
Oreochromis niloticus (O. niloticus), and fish feed. Samples from O. niloticus
and fish feed (n=25 for each) were randomly collected from private fish farms at
Qena province, Egypt, during the winter season. Different Aspergillus spp. were
detected in 60 % and 64 % of O. niloticus and fish feed, respectively. HPLC-based
analysis revealed aflatoxin-producing activity in 75 % and 83 % of A. flavus
isolates from fish and fish feed, respectively. While 96 % of O. niloticus
muscles and fish feed samples were contaminated with aflatoxins, the detected
levels were below the permissible limits, i.e. 20 ug/kg. Moreover, experimental
infection with toxicogenic A. flavus isolates was conducted to evaluate their
pathogenicity in O. niloticus. Expectedly, experimental infections of O.
niloticus with A. flavus were associated with several clinical symptoms reported
in naturally infected fish, e.g. yellow coloration with skin ulceration,
hemorrhagic ulcerative patches on gills and skin, corneal opacity, fin rot and
abdominal distention. Furthermore, aflatoxicogenic A. flavus isolates from fish
were sensitive to herbal clove oil. Even though the measured levels of aflatoxin
were below permissible limits, effort should be placed on further reduction of
exposure to genotoxic and carcinogenic mycotoxins.
PMID- 29333133
TI - Highlight report: Occupational urinary bladder cancer.
PMID- 29333134
TI - Highlight report: The pseudolobule in liver fibrosis.
PMID- 29333135
TI - Highlight report: Metabolomics in hepatotoxicity testing.
PMID- 29333136
TI - Highlight report: The relationship of DNA copy number alterations and mRNA levels
in cancer.
PMID- 29333137
TI - Highlight report: Intratumoral metabolomic heterogeneity of breast cancer.
PMID- 29333138
TI - Highlight report: Monitoring cytochrome P450 activities in living hepatocytes.
PMID- 29333140
TI - Farewell Message from the Editor-in-Chief.
PMID- 29333139
TI - A framework for an alternatives assessment dashboard for evaluating chemical
alternatives applied to flame retardants for electronic applications.
AB - The goal of alternatives assessment (AA) is to facilitate a comparison of
alternatives to a chemical of concern, resulting in the identification of safer
alternatives. A two stage methodology for comparing chemical alternatives was
developed. In the first stage, alternatives are compared using a variety of human
health effects, ecotoxicity, and physicochemical properties. Hazard profiles are
completed using a variety of online sources and quantitative structure activity
relationship models. In the second stage, alternatives are evaluated utilizing an
exposure/risk assessment over the entire life cycle. Exposure values are
calculated using screening-level near-field and far-field exposure models. The
second stage allows one to more accurately compare potential exposure to each
alternative and consider additional factors that may not be obvious from separate
binned persistence, bioaccumulation, and toxicity scores. The methodology was
utilized to compare phosphate-based alternatives for decabromodiphenyl ether
(decaBDE) in electronics applications.
PMID- 29333141
TI - Foreword of the Editor.
PMID- 29333142
TI - IFCC Task Force on Chronic Kidney Disease (Integrated Project) - (TF-CKD) Special
Issue.
PMID- 29333143
TI - Task Force on CKD - We have Come a Long Way.
AB - Chronic Kidney Disease (CKD) is an important medical condition where diagnosis,
staging and monitoring is largely based on routine laboratory tests. During the
last 15 years there have been many important changes in the clinical management
of CKD described in key international guidelines. In order to successfully
implement these guidelines, laboratories must collaborate with clinicians to
provide a co-ordinated service, including accurate measurements and of creatinine
and urine albumin and reporting of an estimated glomerular filtration rate
(eGFR). The IFCC/WASPaLM Task Force on Chronic Kidney Disease (TF-CKD) was
established in 2008 and since that time has worked to improve laboratory testing
in CKD. Key aspects of the work of the TF-CKD include supporting national
laboratory medicine organisations to develop CKD testing guidelines, recognition
of the vital role of collaboration between laboratory and clinical organisations,
the importance of accurate measurements, and endorsement of the KDIGO 2012 CKD
guidelines. A key function of the TF-CKD has been to facilitate sharing and
learning between countries to provide the best outcomes.
PMID- 29333144
TI - Did Creatinine Standardization Give Benefits to the Evaluation of Glomerular
Filtration Rate?
AB - During the last decade, a lot of efforts has been made to improve the evaluation
of renal functions. Measured Glomerular Filtration Rate (GFR) remains the only
valuable test to confirm or confute the status of chronic kidney disease (CKD)
and is recommended by Kidney Disease Global Outcomes guidelines when estimation
of GFR is not reliable. However, in routine clinical practice, serum creatinine
remains the one of the most prescribed biological parameters and is an undeniable
factor, alone or in association with other parameters, of the estimation of GFR.
Since many years, a great improvement in the creatinine measurements was realized
because of the standardization of the methods and fabrication of an international
standard with concentration near to physiological ones (SRM967). Standardization
according to Isotopic Dilution Mass Spectrometry dramatically improves the
analytical performances of creatinine assays resulting in a more accurate
estimation of GFR using creatinine based equations. Indeed, the standardization
of creatinine improves the analytical performance by reducing the bias and
removing the influence of the interfering substances. However, biological
variability of creatinine is not affected by analytical standardization and
remains a limitation to the use of creatinine in some selected populations,
having extreme ages or weights like children, elderly subjects, obese or
malnourished populations. Standardization of creatinine assays result in a clear
improvement of estimated GFR in general population but alternative methods should
be used when creatinine production or metabolism is impaired.
PMID- 29333145
TI - Moving Toward Standardization of Urine Albumin Measurements.
AB - Measurement of urine albumin is important for detecting and monitoring kidney
disease. At the present time, measurement of urine albumin is not standardized
due to the lack of a reference system, which includes both a reference
measurement procedure and certified reference materials. Developing a reference
system will provide a means for clinical laboratory measurement procedures to
become standardized and will enable successful use of uniform clinical decision
points. Currently, urine albumin results vary in excess of 40% depending on which
commercially available measurement procedure is utilized for measurement.
Clinicians may struggle with classification of kidney disease in part due to
differences in measurements from lack of agreement among laboratory methodologies
employed when assessing urine albumin concentrations. This report focuses on
current findings in urine albumin testing, highlights important measurement and
reporting considerations, and presents strategies for developing a reference
measurement procedure to enable standardization of urine albumin measurements.
PMID- 29333146
TI - Cystatin C is Indispensable for Evaluation of Kidney Disease.
AB - The present minireview of the place of cystatin C in clinical medicine
emphasizes, and discuss the evidence, that cystatin C-based GFR-estimating
equations do not require the use of vague terms like race and sex, that cystatin
C-based GFR-esti mating equations are useful for both children and adults,
including the elderly, that the best GFR-estimation requires simultaneous use of
both cystatin C- and creatinine-based equations, that cystatin C-based GFR
estimating equations are superior to creatinine-based equations in predicting end
stage renal disease, cardiovascular manifestations, hospitalisation and death,
and, finally that cystatin C is required to diagnose the new syndrome "Shrunken
Pore Syndrome" with its high mortality and morbidity, even in the absence of
reduced GFR. When automated laboratory equipment is available, the cost of
cystatin C is comparable to that of enzymatically determined creatinine. The
conclusion is that cystatin C should be used at least as often as creatinine in
clinical medicine.
PMID- 29333147
TI - Novel Filtration Markers for GFR Estimation.
AB - Creatinine-based glomerular filtration rate estimation (eGFRcr) has been improved
and refined since the 1970s through both the Modification of Diet in Renal
Disease (MDRD) Study equation in 1999 and the CKD Epidemiology Collaboration (CKD
EPI) equation in 2009, with current clinical practice dependent primarily on eGFR
for accurate assessment of GFR. However, researchers and clinicians have
recognized limitations of relying on creatinine as the only filtration marker,
which can lead to inaccurate GFR estimates in certain populations due to the
influence of non-GFR determinants of serum or plasma creatinine. Therefore,
recent literature has proposed incorporation of multiple serum or plasma
filtration markers into GFR estimation to improve precision and accuracy and
decrease the impact of non-GFR determinants for any individual biomarker. To this
end, the CKD-EPI combined creatinine-cystatin C equation (eGFRcr-cys) was
developed in 2012 and demonstrated superior accuracy to equations relying on
creatinine or cystatin C alone (eGFRcr or eGFRcys). Now, the focus has broadened
to include additional novel filtration markers to further refine and improve GFR
estimation. Beta-2-microglobulin (B2M) and beta-trace-protein (BTP) are two
filtration markers with established assays that have been proposed as candidates
for improving both GFR estimation and risk prediction. GFR estimating equations
based on B2M and BTP have been developed and validated, with the CKD-EPI combined
BTP-B2M equation (eGFRBTP-B2M) demonstrating similar performance to eGFR and
eGFR. Additionally, several studies have demonstrated that both B2M and BTP are
associated with outcomes in CKD patients, including cardiovascular events, ESRD
and mortality. This review will primarily focus on these two biomarkers, and will
highlight efforts to identify additional candidate biomarkers through
metabolomics-based approaches.
PMID- 29333149
TI - A Summary of Worldwide National Activities in Chronic Kidney Disease (CKD)
Testing.
AB - Chronic kidney disease (CKD) is a major public health issue worldwide and is
associated with adverse health outcomes, especially in low- and middle-income
countries. In a cash limited healthcare system, guidelines that improve the
efficiency of health care free up resources needed for other healthcare services.
This short review presents some examples from national acitivities in CKD
testing, including countries throughout the globe: Mexico in North America,
Uruguay in South America, Italy in Europe, Nigeria in Africa and India in Asia.
Considering the fact that treatment of CKD is cost-effective and improves
outcomes, this observation argue in favor of including CKD in national guidelines
and noncommunicable chronic disease (NCD) programs. This diverse example of
national activities fullfil the very first step in achieving this goal.
PMID- 29333148
TI - A Pathway to National Guidelines for Laboratory Diagnostics of Chronic Kidney
Disease - Examples from Diverse European Countries.
AB - The principal benefit of guidelines is to improve the quality of care received by
patients. In the 2012 Clinical Practice Guideline for the Evaluation and
Management of Chronic Kidney Disease (KDIGO) was released and it is designed to
provide information and assist decision making. This review gives a brief
overview of a various national CKD guidelines that rely on the newly released
KDIGO guidelines. All of the included countries (France, Turkey, Norway and
Croatia) are non-English speaking countries and they differ in population and
socio economic aspects. Examples shown in this review may provide valuable
experience for countries that are in process of creating their national CKD
guidelines.
PMID- 29333150
TI - Evaluation of the Correlation Coefficient of Polyethylene Glycol Treated and
Direct Prolactin Results and Comparability with Different Assay System Results.
AB - : The presence of Macro prolactin is a significant cause of elevated prolactin
resulting in misdiagnosis in all automated systems. Poly ethylene glycol (PEG)
pretreatment is the preventive process but such process includes the probability
of loss of a fraction of bioactive prolactin. Surprisingly, PEG treated EQAS &
IQAS samples in Cobas e 411 are found out to be correlating with direct results
of at least 3 immunoassay systems and treated and untreated Cobas e 411 results
are comparable by a correlation coefficient. Comparison of EQAS, IQAS and patient
samples were done to find out the trueness of such correlation factor. Study with
patient's results have established the correlation coefficient is valid for very
small concentration of prolactin also. Materials and methods: EQAS, IQAS and 150
patient samples were treated with PEG and prolactin results of treated and
untreated samples obtained from Roche Cobas e 411. 25 patient's results (treated)
were compared with direct results in Advia Centaur, Architect I & Access2
systems. Statistical calculations: Correlation coefficient was obtained from
trend line of the treated and untreated results. Two tailed p-value obtained from
regression coefficient(r) and sample size. Results and discussion: The
correlation coefficient is in the range (0.761-0.771). Reverse correlation range
is (1.289-1.301). r value of two sets of calculated results were 0.995. Two
tailed p- value is zero approving dismissal of null hypothesis. Conclusion: The z
score of EQAS does not always assure authenticity of resultsPEG precipitation is
correlated by the factor 0.761 even in very small
concentrationsAbbreviationsGFCgel filtration chromatographyPEGpolyethylene
glycolEQASexternal quality assurance systemM-PRLmacro
prolactinPRLprolactinECLIAelectro-chemiluminescence immunoassayCLIAclinical
laboratory improvement amendmentsIQASinternal quality assurance systemrregression
coefficient.
PMID- 29333151
TI - Lab Test Findings in the Elderly.
PMID- 29333152
TI - Erratum: (1) Pediatric Obesity and Cardiometabolic Disorders: Risk Factors and
Biomarkers.
AB - [This corrects the article on p. 6 in vol. 28, PMID: 28439216.].
PMID- 29333153
TI - PPAR-gamma Agonists and Their Role in Primary Cicatricial Alopecia.
AB - Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a ligand
activated nuclear receptor that regulates the transcription of various genes.
PPAR-gamma plays roles in lipid homeostasis, sebocyte maturation, and peroxisome
biogenesis and has shown anti-inflammatory effects. PPAR-gamma is highly
expressed in human sebaceous glands. Disruption of PPAR-gamma is believed to be
one of the mechanisms of primary cicatricial alopecia (PCA) pathogenesis, causing
pilosebaceous dysfunction leading to follicular inflammation. In this review
article, we discuss the pathogenesis of PCA with a focus on PPAR-gamma
involvement in pathogenesis of lichen planopilaris (LPP), the most common
lymphocytic form of PCA. We also discuss clinical trials utilizing PPAR-agonists
in PCA treatment.
PMID- 29333154
TI - Whole-Exome Sequencing-Based Mutational Profiling of Hepatitis B Virus-Related
Early-Stage Hepatocellular Carcinoma.
AB - Background: Hepatocellular carcinoma (HCC) ranks as the third leading cause of
cancer-related mortality in China with increasing incidence. This study is
designed to explore early genetic changes implicated in HCC tumorigenesis and
progression by whole-exome sequencing. Methods: We firstly sequenced the whole
exomes of 5 paired hepatitis B virus-related early-stage HCC and peripheral blood
samples, followed by gene ontological analysis and pathway analysis of the single
nucleotide variants discovered. Then, the mutations of high frequency were
further confirmed by Sanger sequencing. Results: We identified a mutational
signature of dominant T:A>A:T transversion in early HCC and significantly
enriched pathways including ECM-receptor interaction, axon guidance, and focal
adhesion and enriched biological processes containing cell adhesion, axon
guidance, and regulation of pH. Eight genes, including MUC16, UNC79, USH2A,
DNAH17, PTPN13, TENM4, PCLO, and PDE1C, were frequently mutated. Conclusions:
This study reveals a mutational profile and a distinct mutation signature of
T:A>A:T transversion in early-stage HCC with HBV infection, which will enrich our
understanding of genetic characteristics of the early-stage HCC.
PMID- 29333155
TI - Genetic Polymorphisms: A Novel Perspective on Acute Pancreatitis.
AB - Acute pancreatitis (AP) is a complex disease that results in significant
morbidity and mortality. For many decades, it has compelled researchers to
explore the exact pathogenesis and the understanding of the pathogenesis of AP
has progressed dramatically. Currently, premature trypsinogen activation and NF
kappaB activation for inflammation are two remarkable hypotheses for the
mechanism of AP. Meanwhile, understanding of the influence of genetic
polymorphisms has resulted in tremendous development in the understanding of the
advancement of complex diseases. Now, genetic polymorphisms of AP have been noted
gradually and many researchers devote themselves to this emerging area. In this
review, we comprehensively describe genetic polymorphisms combined with the
latest hypothesis of pathogenesis associated with AP.
PMID- 29333156
TI - Intravenous Magnesium Sulphate for Analgesia after Caesarean Section: A
Systematic Review.
AB - Objective: To summarise the evidence for use of intravenous magnesium for
analgesic effect in caesarean section patients. Background: Postcaesarean pain
requires effective analgesia. Magnesium, an N-methyl-D-aspartate receptor
antagonist and calcium-channel blocker, has previously been investigated for its
analgesic properties. Methods: A systematic search was conducted of PubMed,
Scopus, MEDLINE, Cochrane Library, and Google Scholar databases for randomised
control trials comparing intravenous magnesium to placebo with analgesic outcomes
in caesarean patients. Results: Ten trials met inclusion criteria. Seven were
qualitatively compared after exclusion of three for unclear bias risk. Four
trials were conducted with general anaesthesia, while three utilised neuraxial
anaesthesia. Five of seven trials resulted in decreased analgesic requirement
postoperatively and four of seven resulted in lower serial visual analogue scale
scores. Conclusions: Adjunct analgesic agents are utilised to improve analgesic
outcomes and minimise opioid side effects. Preoperative intravenous magnesium may
decrease total postcaesarean rescue analgesia consumption with few side effects;
however, small sample size and heterogeneity of methodology in included trials
restricts the ability to draw strong conclusions. Therefore, given the apparent
safety and efficacy of magnesium, its role as an adjunct analgesic in caesarean
section patients should be further investigated with the most current anaesthetic
techniques.
PMID- 29333157
TI - Potential Developmental and Reproductive Impacts of Triclocarban: A Scoping
Review.
AB - Triclocarban (TCC) is an antimicrobial agent used in personal care products.
Although frequently studied with another antimicrobial, triclosan, it is not as
well researched, and there are very few reviews of the biological activity of
TCC. TCC has been shown to be a possible endocrine disruptor, acting by enhancing
the activity of endogenous hormones. TCC has been banned in the US for certain
applications; however, many human populations, in and outside the US, exhibit
exposure to TCC. Because of the concern of the health effects of TCC, we
conducted a scoping review in order to map the current body of literature on the
endocrine, reproductive, and developmental effects of TCC. The aim of this
scoping review was to identify possible endpoints for future systematic review
and to make recommendations for future research. A search of the literature until
August 2017 yielded 32 relevant studies in humans, rodents, fish, invertebrates,
and in vitro. Based on the robustness of the literature in all three evidence
streams (human, animal, and in vitro), we identified three endpoints for possible
systematic review: estrogenic activity, androgenic activity, and offspring
growth. In this review, we describe the body of evidence and make recommendations
for future research.
PMID- 29333158
TI - Testosterone: Relationships with Metabolic Disorders in Men-An Observational
Study from SPECT-China.
AB - Background: The strength of associations between total testosterone (TT) and
metabolic parameters may vary in different nature of population structure;
however, no study has ever given this information in Chinese population,
especially those without metabolic syndrome (MS). We aimed to analyze the
association magnitudes between TT and multiple metabolic parameters in general
Chinese men. Methods: 4309 men were recruited from SPECT-China study in 2014
2015, which was performed in 22 sites in East China. TT, weight status, and
various metabolic parameters were measured. Linear and logistic regressions were
used to analyze the associations. Results: Men in lower TT quartiles had worse
metabolic parameters including body mass index, triglycerides, HbA1c, and HOMA-IR
(all P for trend < 0.001). Body mass index (B -0.32, 95%CI -0.35 to -0.29) and
obesity (OR 0.40, 95%CI 0.35-0.45) had the largest association magnitude per one
SD increment in TT, while blood pressure and hypertension (OR 0.90, 95%CI 0.84
0.98) had the smallest. These associations also persisted in individuals without
metabolic syndrome. Conclusions: Obesity indices had closer relationships with TT
than most other metabolic measures with blood pressure the least close. These
associations remained robust after adjustment for adiposity and in subjects
without metabolic syndrome.
PMID- 29333159
TI - Ultrasound-Guided Percutaneous Microwave Ablation for Solid Benign Thyroid
Nodules: Comparison of MWA versus Control Group.
AB - Background: The aim of this research is to investigate the feasibility of
percutaneous ultrasound-guided microwave ablation (MWA) for benign solid thyroid
nodules. Methods: Ultrasound-guided percutaneous microwave ablation was performed
for 90 benign solid thyroid nodules in 75 patients. The volume changes of the
nodules were evaluated before and after microwave ablation, and the cosmetic
grading and clinical symptoms were assessed as well. Results: The volume of all
the 90 benign thyroid nodules obviously decreased after microwave ablation at 3-,
6-, 9-, and 12-month follow-ups (p < 0.01), while that of the control group
increased at the follow-up of 12 months (p < 0.01). The volume reduction rate
(VRR) at 3-, 6-, 9-, and 12-month follow-ups was 55.98%, 69.31%, 76.65%, and
84.67% in the MWA group, respectively. The cosmetic problems and clinical
symptoms were also improved in the MWA group. All the patients are well tolerated
to the procedure. Hoarseness occurred in 2 cases (2.7%) and Horner syndrome in 1
case (1.3%), and 1 patient (1.3%) developed slight burn on cervical skin.
Conclusions: Ultrasound-guided percutaneous microwave ablation is a practical
method for treating benign solid thyroid nodules, and the complications were
acceptable. The trial is registered with clinicaltrials.gov with the registration
number NCT03057925.
PMID- 29333160
TI - Corrigendum to "The Current Practice of Screening, Prevention, and Treatment of
Androgen-Deprivation-Therapy Induced Osteoporosis in Patients with Prostate
Cancer".
AB - [This corrects the article DOI: 10.1155/2012/958596.].
PMID- 29333161
TI - Robustness of Tomato Quality Evaluation Using a Portable Vis-SWNIRS for Dry
Matter and Colour.
AB - The utility of a handheld visible-short wave near infrared spectrophotometer
utilising an interactance optical geometry was assessed in context of the
noninvasive determination of intact tomato dry matter content, as an index of
final ripe soluble solids content, and colouration, as an index of maturation to
guide a decision to harvest. Partial least squares regression model robustness
was demonstrated through the use of populations of different harvest dates or
growing conditions for calibration and prediction. Dry matter predictions of
independent populations of fruit achieved R2 ranging from 0.86 to 0.92 and bias
from -0.14 to 0.03%. For a CIE a* colour model, prediction R2 ranged from 0.85 to
0.96 and bias from -1.18 to -0.08. Updating the calibration model with new
samples to extend range in the attribute of interest and in sample matrix is key
to better prediction performance. The handheld spectrometry system is recommended
for practical implementation in tomato cultivation.
PMID- 29333162
TI - A Multivariate Methodological Workflow for the Analysis of FTIR Chemical Mapping
Applied on Historic Paint Stratigraphies.
AB - In the field of applied researches in heritage science, the use of multivariate
approach is still quite limited and often chemometric results obtained are often
underinterpreted. Within this scenario, the present paper is aimed at
disseminating the use of suitable multivariate methodologies and proposes a
procedural workflow applied on a representative group of case studies, of
considerable importance for conservation purposes, as a sort of guideline on the
processing and on the interpretation of this FTIR data. Initially, principal
component analysis (PCA) is performed and the score values are converted into
chemical maps. Successively, the brushing approach is applied, demonstrating its
usefulness for a deep understanding of the relationships between the multivariate
map and PC score space, as well as for the identification of the spectral bands
mainly involved in the definition of each area localised within the score maps.
PMID- 29333163
TI - Infiltrating Cardiac Synovial Sarcoma Presenting as Acute Cerebrovascular
Accident.
AB - Primary cardiac sarcoma is a rare malignant myocardial neoplasm that does not
exhibit gender predominance or age predilection. The classification of these
tumors includes several subtypes, of which synovial sarcoma is a rare
manifestation. When present, these tumors portend a poor prognosis with high
morbidity and mortality that is attributable to their inherent infiltrative
capacity, especially in the absence of treatment. The general consensus for
treatment is surgical excision and neoadjuvant chemotherapy and radiotherapy. In
this report, a case of synovial sarcoma involving the left ventricular outflow
tract and aortic valve is presented.
PMID- 29333165
TI - Adipose-Derived Stromal Cells for Treatment of Patients with Chronic Ischemic
Heart Disease (MyStromalCell Trial): A Randomized Placebo-Controlled Study.
AB - We aimed to evaluate the effect of intramyocardial injections of autologous VEGF
A165-stimulated adipose-derived stromal cells (ASCs) in patients with refractory
angina. MyStromalCell trial is a randomized double-blind placebo-controlled study
including sixty patients with CCS/NYHA class II-III, left ventricular ejection
fraction > 40%, and at least one significant coronary artery stenosis. Patients
were treated with ASC or placebo in a 2 : 1 ratio. ASCs from the abdomen were
culture expanded and stimulated with VEGF-A165. At 6 months follow-up, bicycle
exercise tolerance increased significantly in time duration 22 s (95%CI -164 to
208 s) (P = 0.034), in watt 4 (95%CI -33 to 41, 0.048), and in METs 0.2 (95%CI
1.4 to 1.8) (P = 0.048) in the ASC group while there was a nonsignificant
increase in the placebo group in time duration 9 s (95%CI -203 to 221 s) (P =
0.053), in watt 7 (95%CI -40 to 54) (P = 0.41), and in METs 0.1 (95%CI -1.7 to
1.9) (P = 0.757). The difference between the groups was not significant (P =
0.680, P = 0.608, and P = 0.720 for time duration, watt, and METs, resp.).
Intramyocardial delivered VEGF-A165-stimulated ASC treatment was safe but did not
improve exercise capacity compared to placebo. However, exercise capacity
increased in the ASC but not in the placebo group. This trial is registered with
ClinicalTrials.gov NCT01449032.
PMID- 29333164
TI - When Long Noncoding RNAs Meet Genome Editing in Pluripotent Stem Cells.
AB - Most of the human genome can be transcribed into RNAs, but only a minority of
these regions produce protein-coding mRNAs whereas the remaining regions are
transcribed into noncoding RNAs. Long noncoding RNAs (lncRNAs) were known for
their influential regulatory roles in multiple biological processes such as
imprinting, dosage compensation, transcriptional regulation, and splicing. The
physiological functions of protein-coding genes have been extensively
characterized through genome editing in pluripotent stem cells (PSCs) in the past
30 years; however, the study of lncRNAs with genome editing technologies only
came into attentions in recent years. Here, we summarize recent advancements in
dissecting the roles of lncRNAs with genome editing technologies in PSCs and
highlight potential genome editing tools useful for examining the functions of
lncRNAs in PSCs.
PMID- 29333166
TI - Influence of Different ECM-Like Hydrogels on Neurite Outgrowth Induced by Adipose
Tissue-Derived Stem Cells.
AB - Mesenchymal stem cells (MSCs) have been proposed for spinal cord injury (SCI)
applications due to their capacity to secrete growth factors and vesicles
secretome-that impacts important phenomena in SCI regeneration. To improve MSC
survival into SCI sites, hydrogels have been used as transplantation vehicles.
Herein, we hypothesized if different hydrogels could interact differently with
adipose tissue-derived MSCs (ASCs). The efficacy of three natural hydrogels,
gellan gum (functionalized with a fibronectin peptide), collagen, and a hydrogel
rich in laminin epitopes (NVR-gel) in promoting neuritogenesis (alone and
cocultured with ASCs), was evaluated in the present study. Their impact on ASC
survival, metabolic activity, and gene expression was also evaluated. Our results
indicated that all hydrogels supported ASC survival and viability, being this
more evident for the functionalized GG hydrogels. Moreover, the presence of
different ECM-derived biological cues within the hydrogels appears to differently
affect the mRNA levels of growth factors involved in neuronal survival,
differentiation, and axonal outgrowth. All the hydrogel-based systems supported
axonal growth mediated by ASCs, but this effect was more robust in functionalized
GG. The data herein presented highlights the importance of biological cues within
hydrogel-based biomaterials as possible modulators of ASC secretome and its
effects for SCI applications.
PMID- 29333167
TI - Myocardial Regeneration via Progenitor Cell-Derived Exosomes.
AB - In the past 20 years, a variety of cell products has been evaluated in terms of
their capacity to treat patients with acute myocardial infarction and chronic
heart failure. Despite initial enthusiasm, therapeutic efficacy has overall been
disappointing, and clinical application is costly and complex. Recently, a subset
of small extracellular vesicles (EVs), commonly referred to as "exosomes," was
shown to confer cardioprotective and regenerative signals at a magnitude similar
to that of their donor cells. The conceptual advantage is that they may be
produced in industrial quantities and stored at the point-of-care for off-the
shelf application, ideally without eliciting a relevant recipient immune response
or other adverse effects associated with viable cells. The body of evidence on
beneficial exosome-mediated effects in animal models of heart diseases is rapidly
growing. However, there is significant heterogeneity in terms of exosome source
cells, isolation process, therapeutic dosage, and delivery mode. This review
summarizes the current state of research on exosomes as experimental therapy of
heart diseases and seeks to identify roadblocks that need to be overcome prior to
clinical application.
PMID- 29333169
TI - The DEAD-Box RNA Helicase DDX3 Interacts with m6A RNA Demethylase ALKBH5.
AB - DDX3 is a member of the family of DEAD-box RNA helicases. DDX3 is a multifaceted
helicase and plays essential roles in key biological processes such as cell
cycle, stress response, apoptosis, and RNA metabolism. In this study, we found
that DDX3 interacted with ALKBH5, an m6A RNA demethylase. The ATP domain of DDX3
and DSBH domain of ALKBH5 were indispensable to their interaction with each
other. Furthermore, DDX3 could modulate the demethylation of mRNAs. We also
showed that DDX3 regulated the methylation status of microRNAs and there was an
interaction between DDX3 and AGO2. The dynamics of m6A RNA modification is still
a field demanding further investigation, and here, we add a link by showing that
RNA demethylation can be regulated by proteins such as DDX3.
PMID- 29333168
TI - Mesenchymal Stem Cell Benefits Observed in Bone Marrow Failure and Acquired
Aplastic Anemia.
AB - Acquired aplastic anemia (AA) is a type of bone marrow failure (BMF) syndrome
characterized by partial or total bone marrow (BM) destruction resulting in
peripheral blood (PB) pancytopenia, which is the reduction in the number of red
blood cells (RBC) and white blood cells (WBC), as well as platelets (PLT). The
first-line treatment option of AA is given by hematopoietic stem cell (HSCs)
transplant and/or immunosuppressive (IS) drug administration. Some patients did
not respond to the treatment and remain pancytopenic following IS drugs. The
studies are in progress to test the efficacy of adoptive cellular therapies as
mesenchymal stem cells (MSCs), which confer low immunogenicity and are reliable
allogeneic transplants in refractory severe aplastic anemia (SAA) cases.
Moreover, bone marrow stromal cells (BMSC) constitute an essential component of
the hematopoietic niche, responsible for stimulating and enhancing the
proliferation of HSCs by secreting regulatory molecules and cytokines, providing
stimulus to natural BM microenvironment for hematopoiesis. This review summarizes
scientific evidences of the hematopoiesis improvements after MSC transplant,
observed in acquired AA/BMF animal models as well as in patients with acquired
AA. Additionally, we discuss the direct and indirect contribution of MSCs to the
pathogenesis of acquired AA.
PMID- 29333170
TI - Multiple Myeloma-Derived Exosomes Regulate the Functions of Mesenchymal Stem
Cells Partially via Modulating miR-21 and miR-146a.
AB - Exosomes derived from cancer cells can affect various functions of mesenchymal
stem cells (MSCs) via conveying microRNAs (miRs). miR-21 and miR-146a have been
demonstrated to regulate MSC proliferation and transformation. Interleukin-6 (IL
6) secreted from transformed MSCs in turn favors the survival of multiple myeloma
(MM) cells. However, the effects of MM exosomes on MSC functions remain largely
unclear. In this study, we investigated the effects of OPM2 (a MM cell line)
exosomes (OPM2-exo) on regulating the proliferation, cancer-associated fibroblast
(CAF) transformation, and IL-6 secretion of MSCs and determined the role of miR
21 and miR-146a in these effects. We found that OPM2-exo harbored high levels of
miR-21 and miR-146a and that OPM2-exo coculture significantly increased MSC
proliferation with upregulation of miR-21 and miR-146a. Moreover, OPM2-exo
induced CAF transformation of MSCs, which was evidenced by increased fibroblast
activated protein (FAP), alpha-smooth muscle actin (alpha-SMA), and stromal
derived factor 1 (SDF-1) expressions and IL-6 secretion. Inhibition of miR-21 or
miR-146a reduced these effects of OPM2-exo on MSCs. In conclusion, MM could
promote the proliferation, CAF transformation, and IL-6 secretion of MSCs
partially through regulating miR21 and miR146a.
PMID- 29333171
TI - Exclusive Breastfeeding Practice and Associated Factors among Mothers Attending
Private Pediatric and Child Clinics, Addis Ababa, Ethiopia: A Cross-Sectional
Study.
AB - Background: The prevalence of exclusive breastfeeding (EBF) is globally low (35%)
in sub-Saharan Africa, whereas it is 58% in Ethiopia. Exclusive breastfeeding has
the potential to prevent 11.6% of under-five deaths in developing countries.
Therefore, the main objective of this study was to assess the exclusive
breastfeeding practice and associated factors on mothers attending private
pediatric and child clinics in Addis Ababa, Ethiopia. Methods: An institutional
based cross-sectional study design was used. A total of 380 samples were
obtained. Data were collected using a self-administered questionnaire. Data was
entered and analyzed using SPSS version 16. Descriptive statistics and logistic
regression analysis were used. Results: From 380 mothers, only 44.2% of the
mothers practiced EBF. Two hundred (52.6%) mothers started breastfeeding within 1
hour of delivery; 161 (42.4%) of the mothers gave extra food before six months,
and 244 (64.2%) believed that exclusive breastfeeding was sufficient. Moreover,
288 (75.8%) mothers breastfed their children eight or more times per day.
Spontaneous vaginal delivery was a significant factor to practice EBF (AOR: 1.86,
95% CI: 1.19-2.89). Conclusion: EBF practice in this study was low. Spontaneous
vaginal delivery was a significant factor for EBF; hence, it is very crucial to
promote EBF.
PMID- 29333172
TI - Examining the Relationship between Park Neighborhoods, Features, Cleanliness, and
Condition with Observed Weekday Park Usage and Physical Activity: A Case Study.
AB - Background: Little research has comprehensively explored how park features,
quality indicators, and neighborhood environments are associated with observed
park usage and physical activity (PA). This case study examined whether weekday
park usage and PA differ by neighborhood type, across numerous categories of park
features, and according to park feature condition and cleanliness. Methods:
Direct observation was used to capture the number of users and PA levels within
143 park features in 6 parks (3 urban, 3 suburban) over the course of six weeks.
Audits of park environments assessed the type, condition, and cleanliness of all
features and amenities. Results: Urban parks experienced greater usage, but a
higher proportion of sedentary users than suburban parks. Usage and PA levels
differed across types of park features, with splash pads, pools, paths, and play
structures having the greatest proportion of active users. Usage did not differ
by park feature condition and cleanliness, but greater condition and cleanliness
were generally associated with higher PA levels. Conclusions: Factors such as
neighborhood context, types of park features, and condition and cleanliness can
impact park usage and PA levels and should be targets for researchers and
planners aiming to foster more user-friendly and active neighborhood park
environments.
PMID- 29333173
TI - Prevalence and Perinatal Outcomes of Singleton Term Breech Delivery in Wolisso
Hospital, Oromia Region, Southern Ethiopia: A Cross-Sectional Study.
AB - Background: Breech deliveries have always been topical issues in obstetrics.
Neonates undergoing term breech deliveries have long-term morbidity up to the
school age irrespective of mode of delivery. Objective: To determine prevalence
and perinatal outcomes of singleton term breech delivery. Methods: Hospital based
cross-sectional study was conducted on 384 participants retrospectively.
Descriptive and analytical statistics was used. Result: A total of 384 breech
deliveries were included. Prevalence of singleton breech deliveries in the
hospital was 3.4%. The perinatal outcome of breech deliveries was 322 (83.9%).
Adverse perinatal outcome of singleton term breech delivery was significantly
associated with women's age of greater than or equal to 35 years (AOR = 2.62, 95%
CI = 1.14-6.03), fully dilated cervix (AOR = 0.48, 95% CI = 0.25-0.91), ruptured
membrane (AOR = 5.11, 95% CI = 2.25-11.6), and fetal weight of <2500 g (AOR =
6.77, 95% CI = 3.22-14.25). Conclusion: Entrapment of head, birth asphyxia, and
cord prolapse were the most common causes of perinatal mortality. Factors like
fetal weight <2500 gm, mothers of age 35 years and above, those mothers not
having a fully dilated cervix, and mothers with ruptured membrane were associated
with increased perinatal mortality.
PMID- 29333174
TI - A quantitative framework for assessing ecological resilience.
AB - Quantitative approaches to measure and assess resilience are needed to bridge
gaps between science, policy and management. In this paper, we revisit
definitions of resilience and suggest a quantitative framework for assessing
ecological resilience sensu Holling (1973). Ecological resilience as an emergent
ecosystem phenomenon can be decomposed into complementary attributes (scales,
adaptive capacity, thresholds and alternative regimes) that embrace the
complexity inherent to ecosystems. Quantifying these attributes simultaneously
provides opportunities to move from the assessment of specific resilience within
an ecosystem towards a broader measurement of its general resilience. We provide
a framework, based on testable hypotheses, which allows assessment of
complementary attributes of ecological resilience. By implementing the framework
in adaptive approaches to management, inference and modeling, key uncertainties
can be reduced incrementally over time and learning about the general resilience
of dynamic ecosystems maximized. Such improvements are needed because uncertainty
about global environmental change impacts and their effects on resilience is
high. Improved resilience assessments will ultimately facilitate an optimized use
of limited resources for management.
PMID- 29333175
TI - East-West, Collectivist-Individualist: A Cross-Cultural Examination of
Temperament in Toddlers from Chile, Poland, South Korea, and the U.S.
AB - The present study examined toddler temperament across Chilean, South Korean,
Polish, and US samples, providing an opportunity to examine both collectivist
individualist and East-West contrasts. The effect of culture on the three factor
and 18 dimension scores provided by the Early Childhood Behavior Questionnaire
were investigated. Results provide evidence of cross-cultural differences between
the four samples. Chilean toddlers scored significantly higher than US, Polish,
and South Korean children on the overall factor of Negative Affectivity, as well
as higher than the Polish and South Korean samples on the Surgency factor. South
Korean toddlers scored significantly higher on the factor of Effortful Control,
and two related dimensions, than US, Polish, or Chilean samples. Results are
discussed in terms of the apparent roles of individualism/collectivism and East
West distinctions in shaping temperament development.
PMID- 29333176
TI - Reverse Engineering the Inflammatory "Clock": From Computational Modeling to
Rational Resetting.
AB - Properly-regulated inflammation is central to homeostasis. Traumatic injury,
hemorrhagic shock, septic shock, and other injury-related processes such as wound
healing are associated with dysregulated inflammation. Like many biological
processes, inflammation is a dynamic, complex system whose function, like that of
an analog clock, cannot be discerned simply from a laundry list of its parts
(data). The advent of multiplexed platforms for gathering biological data, while
providing an unprecedented level of detailed information about the inflammatory
response, has paradoxically also proven to be overwhelming. This problem is
especially acute when the datasets involve time courses, since typical
statistical analyses and data-driven modeling are geared towards single time
points. Various groups have addressed this problem using dynamic approaches to
data-driven and mechanistic computational modeling. These modeling tools can be
thought of as the "gears" and "hands" of the "clock," and have led to insights
regarding principal drivers, dynamic networks, feedbacks, and regulatory switches
that characterize and perhaps regulate the inflammatory response. In parallel,
mechanistic computational models have given an abstracted sense of how the
inflammatory "clock" works, leading to in silico models of critically ill
individuals and populations. Integrating data-driven and mechanistic modeling may
point the way to a rational "resetting" of inflammation via model-driven
precision medicine.
PMID- 29333177
TI - The Vasodilatory Effects of Anti-Inflammatory Herb Medications: A Comparison
Study of Four Botanical Extracts.
AB - Inflammation plays a pivotal role in the development and progression of
cardiovascular diseases, in which, the endothelium dysfunction has been a key
element. The current study was designed to explore the vasodilatory effect of
anti-inflammatory herbs which have been traditionally used in different clinical
applications. The total saponins from Actinidia arguta radix (SAA), total
flavonoids from Glycyrrhizae radix et rhizoma (FGR), total coumarins from
Peucedani radix (CPR), and total flavonoids from Spatholobi caulis (FSC) were
extracted. The isometric measurement of vasoactivity was used to observe the
effects of herbal elements on the isolated aortic rings with or without
endothelium. To understand endothelium-independent vasodilation, the effects of
herb elements on agonists-induced vasocontractility and on the contraction of
endothelium-free aortic rings exposed to a Ca2+-free medium were examined.
Furthermore, the role of nitric oxide signaling in endothelium-dependent
vasodilation was also evaluated. In summary, FGR and FSC exhibit potent anti
inflammatory effects compared to CPR and SAA. FGR exerts the strongest
vasodilatory effect, while CPR shows the least. The relaxation induced by SAA and
FSC required intact endothelia. The mechanism of this vasodilation might involve
eNOS. CPR-mediated vasorelaxation appears to involve interference with
intracellular calcium homeostasis, blocking Ca2+ influx or releasing
intracellular Ca2+.
PMID- 29333178
TI - Efficacy of Combined XingZhi-YiNao Granules and Hyperbaric Oxygen Therapy for
Cognition and Motor Dysfunction in Patients with Delayed Encephalopathy after
Acute Carbon Monoxide Poisoning.
AB - Purpose: To investigate the efficacy of XingZhi-YiNao (XZYN) granules and
hyperbaric oxygenation (HBO) for cognition and motor dysfunction in patients with
delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). Methods:
Eighty-nine patients with DEACMP were randomly divided into control group (n =
19), HBO group (n = 32), and XZYN group (n = 38). All patients received
conventional treatment. HBO group received HBO therapy once daily. XZYN group
received extra XZYN granules plus HBO treatment. The related indexes including
activity of daily living (ADL) scale, Montreal cognitive assessment (MoCA) scale,
and mini mental state examination (MMSE) scale were measured. Cerebral white
matter injury, age related white matter changes (ARWMC) scale, and the amplitude
and latency of P300 were assessed. Results: Compared with control group, the
neurological function scores of ADL, MoCA, and MMSE in HBO and XZYN groups were
significantly improved, the impairment degree of brain white matter and cognition
function were obviously alleviated, the latencies of P300 were significantly
shortened, and the amplitudes of P300 were evidently increased (P < 0.05).
Treatment efficacy of XZYN group was superior to that of HBO group (P < 0.05).
Conclusion: Combined XZYN granules and HBO can significantly improve cognition
and motor functions in patients with DEACMP.
PMID- 29333179
TI - Liensinine and Nuciferine, Bioactive Components of Nelumbo nucifera, Inhibit the
Growth of Breast Cancer Cells and Breast Cancer-Associated Bone Loss.
AB - Once breast cancer cells grow aggressively and become lodged in the skeleton
through migration and invasion, they interact with bone microenvironment and
accelerate much more tumor growth and bone destruction. We investigated whether
liensinine and nuciferine, major active components in Nelumbo nucifera (lotus),
could prevent breast cancer cell-mediated bone destruction. Liensinine and
nuciferine inhibited the growth of MDA-MB-231 and MCF-7 human breast cancer cells
by inducing apoptosis and inhibiting proliferation via cell cycle arrest.
Liensinine treatment led to the increased Bax/Bcl-2 ratio, activation of caspase
3, and subsequent cleavage of PARP. Liensinine also displayed significant
inhibition on the migration and invasion of both MDA-MB-231 and MCF-7 human
breast cancer cells compared with nuciferine. In addition, liensinine and
nuciferine inhibited the receptor activator of nuclear factor kappa-B ligand-
(RANKL-) induced osteoclast differentiation in mouse bone marrow macrophage cells
and mature osteoclast-mediated bone resorption. Furthermore, oral administration
of liensinine reduced the osteolysis in nude mice with intratibial injection of
MDA-MB-231 cells. Collectively, liensinine and nuciferine may be promising
candidates for preventing and treating breast cancer bone metastasis and the
resulting osteolytic bone loss by targeting both cancer cells and osteoclasts.
Liensinine has more potent anticancer and antibone resorptive activities than
nuciferine.
PMID- 29333180
TI - Retracted: Silymarin Accelerates Liver Regeneration after Partial Hepatectomy.
AB - [This retracts the article DOI: 10.1155/2015/603529.].
PMID- 29333181
TI - Study on the Inhibitory Effects of Ephedra Aconite Asarum Decoction on LPS
Induced Dendritic Cells.
AB - Dendritic cells (DCs) can secrete cytokines stimulated by lipopolysaccharide
(LPS), which leads to not just acute inflammatory responses but also Th1
polarization. Furtherly, chronic inflammation or autoimmune diseases could be
triggered. As a classic Traditional Chinese Medicine formula, Ephedra Aconite
Asarum Decoction with the main ingredients of ephedrine and hypaconitine can show
effect on anti-inflammation and immunoregulation. But it remains unclear whether
Ephedra Aconite Asarum Decoction controls DCs. In this study, we investigated the
effects of Ephedra Aconite Asarum Decoction on LPS-induced bone marrow-derived
DCs (BMDCs) in vitro. We found that Ephedra Aconite Asarum Decoction lowered
surface costimulators on DCs and reduced the expression of Th1 type cytokines.
Yet it is slightly beneficial for shifting to Th2. Our work reveals that the
Ephedra Aconite Asarum Decoction can regulate Th1 inflammation through
intervening DCs.
PMID- 29333182
TI - Corrigendum to "Ginkgolide C Suppresses Adipogenesis in 3T3-L1 Adipocytes via the
AMPK Signaling Pathway".
AB - [This corrects the article DOI: 10.1155/2015/298635.].
PMID- 29333183
TI - Retracted: The Effect of Elephantopus scaber L. on Liver Regeneration after
Partial Hepatectomy.
AB - [This retracts the article DOI: 10.1155/2013/369180.].
PMID- 29333184
TI - Meta-Analysis of Chinese Traditional Medicine Bushen Huoxue Prescription for
Endometriosis Treatment.
AB - Objectives: To evaluate the efficacy and safety of Bushen Huoxue prescription
(BSHXP) for endometriosis. Methods: A meta-analysis was performed, and studies
were searched from the seven databases from the date of database establishment to
April 30, 2017. Randomized controlled trials (RCTs) that explored the efficacy
and safety of BSHXP for patients with endometriosis were included. Two assessors
independently reviewed each trial. The Cochrane Risk of Bias assessment tool was
used for quality assessment. Results: In the 13 included studies, the total
effectiveness rates of BSHXP were higher than those of Western medicine (RR,
1.55; 95% CI, 1.03-2.32; P = 0.04), but the dysmenorrhea alleviation rates of the
two treatments did not significantly differ (RR, 1.28; 95% CI, 0.70-2.34; P =
0.42). The pregnancy rates of BSHXP were also higher than those of hormone
therapy (RR, 1.99; 95% CI, 1.17-3.39; P = 0.01). However, whether BSHXP is more
effective than Western medicine in diminishing endometriotic cyst remains
unknown. Conclusions: Our study provides evidence that BSHXP is effective and
safe for endometriosis, but this evidence is inconclusive because of the low
methodological quality of the included RCTs. Our findings suggest that BSHXP is
an alternative drug for endometriosis, but it should be further examined in
future clinical research.
PMID- 29333185
TI - Antidepressant-Like Effect of Selected Egyptian Cultivars of Flaxseed Oil on a
Rodent Model of Postpartum Depression.
AB - Flaxseed (Linum usitatissimum L.) is a multipurpose crop with health promoting
potential. This study was undertaken to investigate the fatty acid profile and
yield of fixed oil of six Egyptian flaxseed cultivars. The selected cultivars
with the highest content of polyunsaturated fatty acids (PUFAs) (G9 and G10) were
assessed for their antidepressant-like effect in rat model of postpartum
depression (PPD) induced by hormone-simulated pregnancy followed by hormone
withdrawal and compared to fluoxetine. As compared to control group,
administration of G9 and G10 (270 mg/kg/day, p.o) for two weeks during the
postpartum period can alleviate anxiety and depressive-like behaviors and
biochemical changes in PPD-induced rats. This was confirmed by evaluation of
anxiety-like behaviors (elevated plus maze, open field test, and forced swim test
tests), in addition to biochemical analysis (brain monoamine oxidase-A,
corticosterone level, proinflammatory cytokines, and hippocampal redox state). In
conclusion, flaxseed oil of Egyptian cultivars G9 and G10 exhibited significant
antidepressant-like effect in rat model of PPD without affecting locomotor
activity. At the treatment doses, the antidepressant-like activity of Giza 9 oil
is comparable to fluoxetine.
PMID- 29333186
TI - Role of Cholinergic Anti-Inflammatory Pathway in Treatment of Intestinal Ischemia
Reperfusion Injury by Electroacupuncture at Zusanli.
AB - Electroacupuncture (EA) at Zusanli is a widely used method for the treatment of
intestinal ischemic disease. The current study attempts to investigate the
possible mechanism from the point of cholinergic anti-inflammatory pathway (CAP)
in rats. Thirty rats were divided into five groups: control group, I/R group, EA
group (I/R + EA), PNU group (I/R + alpha7 nAChR agonist), and alpha-BGT group
(I/R + EA + alpha7 nAChR antagonist). EA and medicine injection were performed
immediately after ischemia. After 2 h of reperfusion, blood and intestine samples
were collected and intestinal histopathological score, mRNA expression of mucosal
alpha7 nAChR and NF-kappaBp65, and serum cytokine levels (IL-6, TNF-alpha) were
examined. Compared with the I/R group, the EA group and PNU group could
significantly attenuate the mucosal damage, promote alpha7 nAChR mRNA expression,
and reduce levels of NF-kappaBp65, IL-6, and TNF-alpha. Compared with the EA
group, alpha7 nAChR mRNA was decreased, while concentrations of NF-kappaBp65, IL
6, and TNF-alpha increased in the alpha-BGT group. EA at Zusanli could inhibit NF
kappaBp65 and proinflammatory cytokines production after intestinal I/R injury;
its mechanism may be related to the cholinergic anti-inflammatory pathway.
PMID- 29333187
TI - Efficacy and Safety of the TCM Qi-Supplementing Therapy in Patients with
Myasthenia Gravis: A Systematic Review and Meta-Analysis.
AB - Background: The Traditional Chinese Medicine (TCM) Qi-supplementing therapy has
been used widely for treating myasthenia gravis (MG) in China. The purpose of
this meta-analysis was to evaluate the efficacy and safety of Qi-supplementing
therapy as an adjunctive therapy in MG patients. Methods: Seven electronic
databases were searched through June 2016. Randomized controlled trials (RCTs)
evaluating the add-on effect of Qi-supplementing therapy in MG patients were
included. The outcome measures were the total effective rate, relapse rate, and
adverse events. Results: Twenty-three RCTs involving 1,691 MG patients were
included. The included studies were of low-to-moderate quality. Meta-analysis
showed that Qi-supplementing therapy combined with Western medicine (WM)
significantly improved the total response rate and reduced the relapse risk
during 6-24 months of follow-up. Subgroup analysis showed that Qi-supplementing
therapy only affected the total response rate within the first 6 months of
treatment. Moreover, the rate of adverse events was lower with the addition of Qi
supplementing therapy to WM than with WM only. Conclusions: Short-term Qi
supplementing therapy combined with WM appears to be superior to WM for improving
the total response rate and reducing the relapse rate. However, more high-quality
RCTs are warranted owing to methodological flaws of previous trials.
PMID- 29333188
TI - Dracorhodin Perchlorate Accelerates Cutaneous Wound Healing in Wistar Rats.
AB - Dracorhodin perchlorate (DP) is extracted from Dragon's blood, which is widely
used in traditional Chinese medicine, especially in wound healing. The aim of
this paper is to investigate the influence of DP ointment, which contained DP
dissolved in DMSO and mixed with Vaseline, on cutaneous wound healing in Wistar
rats. Forty Wistar rats were divided into two groups: control and DP groups. The
skin on the back of each rat was punched with two full-thickness wounds and then
treated with the corresponding drug. After 3, 7, 10, 14, and 21 days, four rats
were sacrificed for immunological, biochemical, and histological analyses.
Compared with the control treatment, DP could significantly promote wound
closure. Histological and biochemical analyses of the skin biopsies also showed
that DP regulated the expression of inflammatory responses by TNF-alpha and IL
beta and by supporting wound tissue growth and collagen deposition. Western blot
revealed that DP could also facilitate the expression of EGF and VEGF proteins.
In conclusion, DP promotes wound healing.
PMID- 29333189
TI - Tubular variant of mammary adenomyoepithelioma: Diagnostic challenges and
cytomorphological correlation in two cases.
AB - The authors describe the cytomorphologic features of two cases of tubular variant
of adenomyoepithelioma of the breast that were first examined by fine-needle
aspiration cytology (FNAC) and diagnosed as fibroadenoma. On retrospective review
of the cytology, subtle features such as less cohesive epithelial clusters,
intimate association of clusters of stromal cells with epithelial elements, a
dominant population of plump-epithelioid naked (myoepithelial) cells, and
occasional cells with intranuclear inclusions, were noted. Thus, these lesions
can be diagnostically challenging and cannot be conclusively differentiated from
either fibroadenoma or tubular adenoma cytologically and the pathologist may only
be able to give a differential on FNAC. Recognition of the biphasic nature and
the characteristic overall architecture of the tumors in combination with
immunohistochemistry are essential to establish the correct diagnosis on biopsy.
Although most tumors have a benign clinical course, rare instances of local
recurrence, malignant transformation, and distant metastases have been reported.
A complete excision with adequate margins would lower the chance of local
recurrence.
PMID- 29333190
TI - Fine-needle aspiration of a right neck mass in a 10-year-old boy: Diagnostic
clues and workup for tumors with small round blue cells.
PMID- 29333191
TI - Comparative evaluation of six parametric Robinson and three parametric Howell's
modification of Scarf-BloomRichardson grading method on breast aspirates with
histopathology: A prospective study.
AB - Background: Fine needle aspiration cytology (FNAC) is a quick method to assess
the tumor grade before its removal which will help clinicians to decide on the
appropriate neo adjuvant therapy. This is essentially true in developing
countries where core needle biopsy still is not used as a standard practice to
sample breast carcinoma. Assessment of biological aggressiveness by cytological
grading (CG) without removing the would be of immense value. The National Cancer
Institute, Bethesda, sponsored conference had recommended that tumor grading on
FNA material should be incorporated in cytology reports for prognostication. Aim:
The present study was carried out to evaluate which among the two, five
parametric Robinson or three parametric Scarf-BloomRichardson (SBR) cytology
grading method corresponds better with the histological grading (HG) in breast
carcinoma. Materials and Methods: FNAC of 150 cases of ductal carcinoma breast
with subsequent histological confirmation was studied to assess the tumor grade
on cytology by two distinct methods Robinson and Howell's modification of
SBRmethod and then correlated with histologic grade. Results: Comparative
analysis revealed concordance of 76% by Robinson and 68% by SBR with Kappa value
of 0.6683 and 0.4505 and diagnostic accuracy of 86.7% and 78.7%, respectively.
Conclusions: We conclude that Robinson method showed a better correlation and
higher kappa value of agreement in comparison with SBR method. Robinson method of
CG is simpler, objective, and easily reproducible for grading breast carcinomas.
PMID- 29333192
TI - 'Haven of safety' and 'secure base': a qualitative inquiry into factors affecting
child attachment security in Nairobi, Kenya.
AB - Secure attachment in childhood and adolescence protects children from engagement
in high risk behaviors and development of mental health problems over the life
span. Poverty has been shown to create impoverishment in certain aspects of
caregiving and correspondingly to compromise development of secure attachment in
children. Nineteen children 8 to 14 years old from two schools in a middle income
area and an urban informal settlement area of Nairobi were interviewed using an
adapted Child Attachment Interview (CAI) protocol. CAI was developed to provide a
glimpse into the 'meta-theories' children have about themselves, parents,
parenting and their attachment ties with parents and extended family members.
Narratives obtained with the CAI were analyzed using thematic analysis. Both
Bowlby's idea of 'secure base' as well as Bronfrenbrenner's 'ecological niche'
are used as reference points to situate child attachment and parenting practices
in the larger Kenyan context. We found that with slight linguistic alterations
CAI can be used to assess attachment security of Kenyan children in this
particular age range. We also found that the narration ability in both groups of
children was generally good such that formal coding was possible, despite
cultural differences. Our analysis suggested differences in narrative quality
across the children from middle class and lower socio-economic class schools on
specific themes such as: sensitivity of parenting (main aspects of sensitivity
were associated with disciplinary methods and child's access to education), birth
order, parental emotional availability, and severity of inter-parental conflicts
and child's level of exposure. The paper puts in context a few cultural practices
such as greater household responsibility accorded to the eldest child and stern
to harsh disciplinary methods adopted by parents in the Kenyan setting.
PMID- 29333193
TI - Systematic Review of Community-Engaged Research in Ophthalmology.
AB - Introduction: Community-engaged research (CEnR) allows researchers and community
organizations to partner together to improve health outcomes and to decrease
health disparities. While prevalent in other fields of medicine, it is rarely
used in ophthalmology. Areas covered: A comprehensive search of Ovid MEDLINE, NLM
Pubmed, Ovid Embase, Scopus and the Cochrane Library for the Medical Subject
Headings (MeSH) "Community-based participatory research" and text word variations
including participatory research, community engagement, community research,
partnered research, community-institutional relations, CENR, CBPR in addition to
variations on ophthalmology, eye diseases, vision disorders and eye injuries
yielded 451 unique references. Two ophthalmologists (KN, PANC) reviewed the
titles and abstracts and identified 37 relevant studies. Expert consultation
yielded an additional reference. After reviewing the full texts and excluding non
English texts, 18 articles met the necessary criteria. The eighteen articles all
utilized at least one of the nine principles of CEnR. Expert commentary:
Ophthalmology is perfectly positioned to benefit from CEnR. Increased community
engagement in ophthalmic research would expand the reach of our work and address
some of the most difficult problems in vision disparities and outcomes.
PMID- 29333194
TI - Transient Dynamics Simulation of Airflow in a CT-Scanned Human Airway Tree: More
or Fewer Terminal Bronchi?
AB - Using computational fluid dynamics (CFD) method, the feasibility of simulating
transient airflow in a CT-based airway tree with more than 100 outlets for a
whole respiratory period is studied, and the influence of truncations of terminal
bronchi on CFD characteristics is investigated. After an airway model with 122
outlets is extracted from CT images, the transient airflow is simulated. Spatial
and temporal variations of flow velocity, wall pressure, and wall shear stress
are presented; the flow pattern and lobar distribution of air are gotten as well.
All results are compared with those of a truncated model with 22 outlets. It is
found that the flow pattern shows lobar heterogeneity that the near-wall air in
the trachea is inhaled into the upper lobe while the center flow enters the other
lobes, and the lobar distribution of air is significantly correlated with the
outlet area ratio. The truncation decreases airflow to right and left upper lobes
and increases the deviation of airflow distributions between inspiration and
expiration. Simulating the transient airflow in an airway tree model with 122
bronchi using CFD is feasible. The model with more terminal bronchi decreases the
difference between the lobar distributions at inspiration and at expiration.
PMID- 29333195
TI - Corrigendum to "Development of a Patient-Specific Finite Element Model for
Predicting Implant Failure in Pelvic Ring Fracture Fixation".
AB - [This corrects the article DOI: 10.1155/2017/9403821.].
PMID- 29333196
TI - Brief report: Reduced anxiety following Pivotal Response Treatment in young
children with Autism Spectrum Disorder.
AB - Up to 40% of children with Autism Spectrum Disorder (ASD) exhibit co-occurring
anxiety symptoms. Despite recent success in mitigating anxiety symptoms in school
aged children with ASD (mean age >9 years) using adapted versions of Cognitive
Behavioural Therapy, little is known about potential treatment outcomes for
younger children. To address the gap in the literature, this open-label study
evaluated change in anxiety following a 16-week open-label trial of Pivotal
Response Treatment (PRT) in children with ASD aged 4-8 years. PRT is a
behavioural treatment based on the principles of Applied Behaviour Analysis and
has a primary aim of increasing social communication skills in children with ASD
through natural reinforcements. To minimise conflation of anxiety and other co
occurring symptoms such as disruptive behaviour and attention-deficit
hyperactivity disorder, we measured anxiety using the autism anxiety subscale of
the Child and Adolescent Symptom Inventory (CASI) devised by Sukhodolsky et al.
(2008). We observed significant anxiety reduction over 16-weeks of PRT.
Furthermore, anxiety reduction was independent of changes in autism symptom
severity. This study shows promising results for PRT as an intervention for
reducing anxiety in young children with ASD.
PMID- 29333197
TI - Solving moment hierarchies for chemical reaction networks.
AB - The study of chemical reaction networks (CRN's) is a very active field. Earlier
well-known results (Feinberg 1987 Chem. Enc. Sci. 42 2229, Anderson et al 2010
Bull. Math. Biol. 72 1947) identify a topological quantity called deficiency, for
any CRN, which, when exactly equal to zero, leads to a unique factorized steady
state for these networks. No results exist however for the steady states of non
zero-deficiency networks. In this paper, we show how to write the full moment
hierarchy for any non-zero-deficiency CRN obeying mass-action kinetics, in terms
of equations for the factorial moments. Using these, we can recursively predict
values for lower moments from higher moments, reversing the procedure usually
used to solve moment hierarchies. We show, for nontrivial examples, that in this
manner we can predict any moment of interest, for CRN's with non-zero deficiency
and non-factorizable steady states.
PMID- 29333198
TI - Response of Pacific-sector Antarctic ice shelves to the El Nino/Southern
Oscillation.
AB - Satellite observations over the past two decades have revealed increasing loss of
grounded ice in West Antarctica, associated with floating ice shelves that have
been thinning. Thinning reduces an ice-shelf's ability to restrain grounded-ice
discharge, yet our understanding of the climate processes that drive mass changes
is limited. Here, we use ice-shelf height data from four satellite altimeter
missions (1994-2017) to show a direct link between ice-shelf-height variability
in the Antarctic Pacific sector and changes in regional atmospheric circulation
driven by the El Nino-Southern Oscillation. This link is strongest from Dotson to
Ross ice shelves and weaker elsewhere. During intense El Nino years, height
increase by accumulation exceeds the height decrease by basal melting, but net
ice-shelf mass declines as basal ice loss exceeds lower-density snow gain. Our
results demonstrate a substantial response of Amundsen Sea ice shelves to global
and regional climate variability, with rates of change in height and mass on
interannual timescales that can be comparable to the longer-term trend, and with
mass changes from surface accumulation offsetting a significant fraction of the
changes in basal melting. This implies that ice-shelf height and mass variability
will increase as interannual atmospheric variability increases in a warming
climate.
PMID- 29333199
TI - Effects of the dietary approaches to stop hypertension (DASH) diet on glucose
variability in youth with Type 1 diabetes.
AB - Objective: Glucose variability (GV) independently increases risk for vascular
events in patients with diabetes. The Dietary Approaches to Stop Hypertension
(DASH) dietary pattern emphasizes fruits, vegetables, whole grains, lean meats,
and low fat dairy and has the potential to reduce postprandial blood glucose (BG)
excursions, however, its effect on GV is not known. The purpose of this work was
to assess feasibility and collect preliminary data on the efficacy of the DASH
diet on GV in adolescents with type 1 diabetes (T1D). Methods: Twenty one
adolescents recruited from the Diabetes Center of Cincinnati Children's Hospital
Medical Center with T1D (11-17y) participated in one of two phases of a
controlled feeding study. The first phase tested the acceptability and blood
glucose response to a traditional DASH diet (DASH) and the second phase tested a
DASH diet specifically modified for diabetes (DASH-D) to improve glucose response
to meals. For each phase, participants consumed first their usual diet, and then
a controlled DASH diet while wearing continuous glucose monitoring (CGM) systems
for 3 days of each diet. All foods were provided to the patients during the DASH
dietary periods and 24 h dietary recalls were conducted during the usual diet
periods to assess daily intake. Results: Sixteen participants (14.1 +/- 2.2y)
were included in final analyses (DASH n=7, DASH-D n=9). Both DASH diets were
significantly higher in fruits, vegetables, fiber, vitamin A, and % energy from
protein than usual intakes. DASH was higher in carbohydrate (CHO) (60 vs. 50%)
and lower in fat (21 vs. 36%) than usual intake, resulting in higher GV (Standard
Deviation and Lability Index) and more low BG excursions (3 +/- 2.8 vs. 7.1 +/-
3.3, p=0.024). DASH-D was modified to better match CHO and fat content of
patients' usual intakes in phase 1 (50/30/20 for CHO/fat/pro respectively, which
resulted in no difference in GV between DASH-D and usual intake. There were also
trends for lower average BG (144.1 vs. 168.9, p=0.072) and less percentage of
time spent in the hyperglycemic range (39.3 +/- 25.5 vs. 54.1 +/- 19.4, p=0.07)
on DASH-D compared to usual intake. Conclusion: The DASH dietary pattern tended
to result in less hyperglycemia and an overall lower BG compared to usual care.
Modifying a traditional DASH diet by increasing heart healthy fats improves
glycemic response to DASH and may be beneficial for long term cardiovascular
benefits in youth with T1D.
PMID- 29333200
TI - Perceptions of Mindfulness in a Low-income, Primarily African American Treatment
Seeking Sample.
AB - Individuals with low socioeconomic status (SES) and members of racial/ethnic
minority groups often experience profound disparities in mental health and
physical well-being. Mindfulness-based interventions show promise for improving
mood and health behaviors in higher-SES and non-Latino White populations.
However, research is needed to explore what types of adaptations, if any, are
needed to best support underserved populations. This study used qualitative
methods to gain information about a) perceptions of mindfulness, b) experiences
with meditation, c) barriers to practicing mindfulness, and d) recommendations
for tailoring mindfulness-based interventions in a low-income, primarily African
American treatment-seeking sample. Eight focus groups were conducted with 32
adults (16 men and 16 women) currently receiving services at a community mental
health center. Most participants (91%) were African American. Focus group data
were transcribed and analyzed using NVivo 10. A team of coders reviewed the
transcripts to identify salient themes. Relevant themes included beliefs that
mindfulness practice might improve mental health (e.g., managing stress and anger
more effectively) and physical health (e.g., improving sleep and chronic pain,
promoting healthier behaviors). Participants also discussed ways in which
mindfulness might be consistent with, and even enhance, their religious and
spiritual practices. Results could be helpful in tailoring mindfulness-based
treatments to optimize feasibility and effectiveness for low-SES adults receiving
mental health services.
PMID- 29333201
TI - Dispositional Mindfulness, Shame, and Compulsive Sexual Behaviors among Men in
Residential Treatment for Substance Use Disorders.
AB - Approximately 31% of men in treatment for a substance use disorders (SUD) engage
in compulsive sexual behavior (CSB). Shame, a well-documented consequence of CSB,
increases the likelihood of relapse following treatment for SUDs. Despite the
risk of relapse, prior research has not investigated factors that may attenuate
the relation between CSB and shame. Dispositional mindfulness is one such factor
known to mitigate shame. However, researchers have yet to examine dispositional
mindfulness as a moderator of the relationship between CSB and shame among a
sample of men in treatment for SUDs. In an effort to inform intervention efforts,
the present study aimed to investigate the hypothesis that CSB would not relate
to shame among men with high, as opposed to low, levels of dispositional
mindfulness. The present study reviewed medical records of 184 men in residential
treatment for SUDs who completed cross-sectional measures of shame, CSB,
dispositional mindfulness, and substance use problems. Results demonstrated a
significant interaction between CSB and dispositional mindfulness such that CSB
positively related to shame at low, but not mean or high, levels of dispositional
mindfulness. These results support and extend previous mindfulness and CSB
treatment research. Findings suggested that intervention efforts for CSB may
benefit from increasing dispositional mindfulness in an effort to reduce shame
related cognitions.
PMID- 29333202
TI - Elasto-inertial migration of deformable capsules in a microchannel.
AB - In this paper, we study the dynamics of deformable cells in a channel flow of
Newtonian and polymeric fluids and unravel the effects of deformability,
elasticity, inertia, and size on the cell motion. We investigate the role of
polymeric fluids on the cell migration behavior and the performance of inertial
microfluidic devices. Our results show that the equilibrium position of the cell
is on the channel diagonal, in contrast to that of rigid particles, which is on
the center of the channel faces for the same range of Reynolds number. A constant
viscosity polymeric fluid, modeled using an Oldroyd-B constitutive equation,
drives the cells toward the channel centerline, while a shear-thinning polymeric
fluid, modeled using a Giesekus constitutive equation, pushes the cells toward
the channel wall. The findings of this paper suggest that the addition of
polymers in microfluidic devices can be used to enhance the throughput of cell
focusing and separation devices at a low cost. This study provides an insight on
the role of rheological properties of the fluid and the ways that they can be
tuned to control the focal position of the cells.
PMID- 29333203
TI - Biomimetic microfluidic platform for the quantification of transient endothelial
monolayer permeability and therapeutic transport under mimicked cancerous
conditions.
AB - Therapeutic delivery from microvasculature to cancerous sites is influenced by
many factors including endothelial permeability, vascular flow rates/pressures,
cancer secretion of cytokines and permeabilizing agents, and characteristics of
the chosen therapeutics. This work uses bi-layer microfluidics capable of
studying dye and therapeutic transport from a simulated vessel to a cancerous
region while allowing for direct visualization and quantification of endothelial
permeability. 2.5 to 13 times greater dye transport was observed when utilizing
small dye sizes (FITC) when compared to larger molecules (FITC-Dextran 4 kDa and
FITC-Dextran 70 kDa), respectively. The use of lower flow rates/pressures is
shown to improve dye transport by factors ranging from 2.5 to 5 times, which
result from increased dye diffusion times within the system. Furthermore,
subjecting confluent endothelial monolayers to cancerous cells resulted in
increased levels of vascular permeability. Situations of cancer induced increases
in vascular permeability are shown to facilitate enhanced dye transport when
compared to non-diseased endothelial monolayers. Subsequent introduction of
paclitaxel or doxorubicin into the system was shown to kill cancerous cells
resulting in the recovery of endothelial confluency overtime. The response of
endothelial cells to paclitaxel and doxorubicin is quantified to understand the
direct influence of anti-cancer therapeutics on endothelial growth and
permeability. Introduction of therapeutics into the system showed the recovery of
endothelial confluency and dye transport back to conditions experienced prior to
cancer cell introduction after 120 h of continuous treatment. Overall, the system
has been utilized to show that therapeutic transport to cancerous sites depends
on the size of the chosen therapeutic, the flow rate/pressure established within
the vasculature, and the degree of cancer induced endothelial permeability. In
addition, treatment of the cancerous region has been demonstrated with anti
cancer therapeutics, which are shown to influence vascular permeability in direct
(therapeutics themselves) and indirect (death of cancer cells) manners. Lastly,
the system presented in this work is believed to function as a versatile testing
platform for future anti-cancer therapeutic testing and development.
PMID- 29333204
TI - Aggressive prostate cancer cell nuclei have reduced stiffness.
AB - It has been hypothesized that highly metastatic cancer cells have softer nuclei
and hence would travel faster through confining environments. Our goal was to
prove this untested hypothesis for prostate cells. Our nuclear creep experiments
using a microfluidic channel with a narrow constriction show that stiffness of
aggressive immortalized prostate cancer nuclei is significantly lower than that
of immortalized normal cell nuclei and hence can be a convenient malignancy
marker. Nuclear stiffness is found to be the highest for cells expressing high
levels of lamin A/C but lowest for cells expressing low lamin A/C levels.
Decreased chromatin condensation found in softer nuclei suggests that the former
can also be a marker for aggressive cancers.
PMID- 29333205
TI - High aspect ratio induced spontaneous generation of monodisperse picolitre
droplets for digital PCR.
AB - Droplet microfluidics, which involves micrometer-sized emulsion droplets on a
microfabricated platform, has been demonstrated as a unique system for many
biological and chemical applications. Robust and scalable generation of
monodisperse droplets at high throughput is of fundamental importance for droplet
microfluidics. Classic designs for droplet generation employ shear fluid dynamics
to induce the breakup of droplets in a two-phase flow and the droplet size is
sensitive to flow rate fluctuations, often resulting in polydispersity. In this
paper, we show spontaneous emulsification by a high aspect ratio (>3.5)
rectangular nozzle structure. Due to the confinement and abrupt change of the
structure, a Laplace pressure difference is generated between the dispersed and
continuous phases, and causes the thread thinning and droplet pinch-off without
the need to precisely control external flow conditions. A high-throughput droplet
generator was developed by parallelization of a massive number of the basic
structures. This device enabled facile and rapid partition of aqueous samples
into millions of uniform picolitre droplets in oil. Using this device, on-chip
droplet-based digital polymerase chain reaction (PCR) was performed for absolute
quantification of rare genes with a wide dynamic range.
PMID- 29333206
TI - Nonlinear Joint Latent Variable Models and Integrative Tumor Subtype Discovery.
AB - Integrative analysis has been used to identify clusters by integrating data of
disparate types, such as deoxyribonucleic acid (DNA) copy number alterations and
DNA methylation changes for discovering novel subtypes of tumors. Most existing
integrative analysis methods are based on joint latent variable models, which are
generally divided into two classes: joint factor analysis and joint mixture
modeling, with continuous and discrete parameterizations of the latent variables
respectively. Despite recent progresses, many issues remain. In particular,
existing integration methods based on joint factor analysis may be inadequate to
model multiple clusters due to the unimodality of the assumed Gaussian
distribution, while those based on joint mixture modeling may not have the
ability for dimension reduction and/or feature selection. In this paper, we
employ a nonlinear joint latent variable model to allow for flexible modeling
that can account for multiple clusters as well as conduct dimension reduction and
feature selection. We propose a method, called integrative and regularized
generative topographic mapping (irGTM), to perform simultaneous dimension
reduction across multiple types of data while achieving feature selection
separately for each data type. Simulations are performed to examine the operating
characteristics of the methods, in which the proposed method compares favorably
against the popular iCluster that is based on a linear joint latent variable
model. Finally, a glioblastoma multiforme (GBM) dataset is examined.
PMID- 29333207
TI - Development and Feasibility of a Robotic Laparoscopic Clipping Tool for Wound
Closure and Anastomosis.
AB - This paper reports the design, development, and initial evaluation of a robotic
laparoscopic clipping tool for single manipulator wound closure and anastomosis
(tubular reconnection). The tool deploys biodegradable clips and clasps with the
goal of (i) integrating grasping and suturing into a single device for single
hand or manipulator use, (ii) applying the equivalent of interrupted sutures
without the need of managing suture thread, and (iii) allowing for full six
degrees-of-freedom (DOFs) laparoscopic control when mounted on a robot arm. The
specifications, workflow, and detailed design of the robotic laparoscopic tool
and injection molded bio-absorbable T shaped clip and locking clasp are reported.
The clipping tool integrates forceps to grab and stabilize tissue and a clip and
clasp applier to approximate and fixate the tissue. A curved needle is advanced
on a circular needle path and picks up and drags clips through tissue. The clip
is then tightened through the tissue and a clasp is clamped around the clip,
before the clip is released from the needle. Results of several bench test runs
of the tool show: (a) repeatable circular needle drive, (b) successful pick-up
and deployment of clips, (c) successful shear of the clip to release the clip
from the needle, and (d) closure of clasp on clip with an average of 2.0 N
holding force. These data indicate that the robotic laparoscopic clipping tool
could be used for laparoscopic wound closure and anastomosis.
PMID- 29333208
TI - Integrating Cadaver Needle Forces Into a Haptic Robotic Simulator.
AB - Accurate force simulation is essential to haptic simulators for surgical
training. Factors such as tissue inhomogeneity pose unique challenges for
simulating needle forces. To aid in the development of haptic needle insertion
simulators, a handheld force sensing syringe was created to measure the motion
and forces of needle insertions. Five needle insertions were performed into the
neck of a cadaver using the force sensing syringe. Based on these measurements a
piecewise exponential needle force characterization, was implemented into a
haptic central venous catheterization (CVC) simulator. The haptic simulator was
evaluated through a survey of expert surgeons, fellows, and residents. The
maximum needle insertion forces measured ranged from 2.02 N to 1.20 N. With this
information, four characterizations were created representing average, muscular,
obese, and thin patients. The median survey results showed that users
statistically agreed that "the robotic system made me sensitive to how patient
anatomy impacts the force required to advance needles in the human body." The
force sensing syringe captured force and position information. The information
gained from this syringe was able to be implemented into a haptic simulator for
CVC insertions, showing its utility. Survey results showed that experts, fellows,
and residents had an overall positive outlook on the haptic simulator's ability
to teach haptic skills.
PMID- 29333209
TI - ?
AB - [This corrects the article DOI: 10.11604/pamj.2016.25.142.7193.].
PMID- 29333210
TI - Bayesian analysis of stochastic volatility-in-mean model with leverage and
asymmetrically heavy-tailed error using generalized hyperbolic skew Student's t
distribution.
AB - A stochastic volatility-in-mean model with correlated errors using the
generalized hyperbolic skew Student-t (GHST) distribution provides a robust
alternative to the parameter estimation for daily stock returns in the absence of
normality. An efficient Markov chain Monte Carlo (MCMC) sampling algorithm is
developed for parameter estimation. The deviance information, the Bayesian
predictive information and the log-predictive score criterion are used to assess
the fit of the proposed model. The proposed method is applied to an analysis of
the daily stock return data from the Standard & Poor's 500 index (S&P 500). The
empirical results reveal that the stochastic volatility-in-mean model with
correlated errors and GH-ST distribution leads to a significant improvement in
the goodness-of-fit for the S&P 500 index returns dataset over the usual normal
model.
PMID- 29333211
TI - Pomegranate Juice Prevents the Formation of Lung Nodules Secondary to Chronic
Cigarette Smoke Exposure in an Animal Model.
AB - Background: Cigarette smoke (CS) induces an oxidative stress, DNA damage, and
lung cancer. Pomegranate juice (PJ) possess potent antioxidant activity
attributed to its polyphenols. We investigated whether PJ supplementation would
prevent the formation of lung nodules, attenuate mitotic activity, and reduce
hypoxia-inducible factor-1alpha (HIF-1alpha) expression secondary to CS exposure
in an animal model. Methods: Mice were divided into: Control group, CS group, CS
+ PJ group, and PJ-only group. CS and CS + PJ were exposed to CS, 5 days per
week, for a total of 5 months. Animals were then housed for additional four
months. CS + PJ and PJ groups received PJ throughout the experiment period while
others received placebo. At the end of the experiment, the incidence of lung
nodules was assessed by (1) histological analysis, (2) mitotic activity
[measurement of PHH3 antibodies], and (3) measurement of HIF-1alpha expression.
Results: The incidence of lung nodules was significantly increased in CS. CS
exposure significantly increased PHH3 and HIF-1alpha expression. PJ
supplementation attenuated the formation of lung nodules and reduced PHH3 and HIF
1alpha expression. Conclusion: PJ supplementation significantly decreased the
incidence of lung cancer, secondary to CS, prevented the formation of lung
nodules, and reduced mitotic activity and HIF-1alpha expression in an animal
model.
PMID- 29333212
TI - Effect of Bioactive Compound of Aronia melanocarpa on Cardiovascular System in
Experimental Hypertension.
AB - Aronia melanocarpa has attracted scientific interest due to its dense contents of
different polyphenols. We aimed to analyse effects of Aronia melanocarpa (AME)
extract on blood pressure (BP), lipid peroxidation, cytokine level, total NOS
activity in the left ventricle (LV), and aorta of L-NAME-induced hypertensive
rats. 12-week-old male WKY rats were assigned to the control group and groups
treated with AME extract (57.90 mg/kg/day), L-NAME (40 mg/kg/day), or combination
of L-NAME (40 mg/kg/day) and AME (57.90 mg/kg/day) in tap water for 3 weeks. NOS
activity, eNOS protein expression, and conjugated diene (CD) concentration were
determined in the LV and aorta. After 3 weeks of L-NAME treatment, BP was
increased by 28% and concomitant treatment with AME reduced it by 21%. NOS
activity of the LV and aorta in the L-NAME group was decreased by about 40%,
while AME increased it almost on the control level. AME-induced eNOS upregulation
may contribute to increase NOS activity. Moreover, AME decreased CD concentration
in the LV and aorta and TNF-alpha and IL-6 production in the plasma were
increased by L-NAME treatment. In conclusion, our results showed that active
substances of Aronia melanocarpa may have a positive effect on blood pressure,
NOS activity, and proinflammatory processes in L-NAME-induced hypertension.
PMID- 29333214
TI - Cytoprotective Effects of Cell-Permeable Bifunctional Antioxidant Enzyme, GST-TAT
SOD, against Cisplatin-Induced Cell Damage.
AB - GST-TAT-SOD, a cell-permeable bifunctional antioxidant enzyme, is a potential
selective radioprotector. This study aimed to investigate the cytoprotective
activity of GST-TAT-SOD against cisplatin-induced damage. The current study
showed that cisplatin induced the formation of reactive oxygen species in normal
L-02 cells. GST-TAT-SOD (2000 U/mL) executed its antioxidant role by directly
scavenging excess intracellular free radicals and augmenting cellular antioxidant
defense such as reducing MDA level, enhancing the SOD activity, GST activity, and
T-AOC. Thus, it suppressed the growth inhibition and apoptosis of cisplatin
treated normal cells. Meanwhile, the growth inhibition of tumor cells (SMMC-7721)
caused by cisplatin was unaffected by GST-TAT-SOD pretreatment. GST-SOD, as a
comparison, seemed to be powerless for related indicators as it could not enter
into cells without cell-permeating peptide. These results suggest that GST-TAT
SOD might be a potential cytoprotective agent for cisplatin-induced side effects.
PMID- 29333217
TI - Gender Differences in Clinical Profiles of Stress-Induced Cardiomyopathy.
AB - Background: Although stress-induced cardiomyopathy (SCMP) is reported to be more
common in women, little is known about gender differences in patients with SCMP.
The aim of the study was to describe clinical features of patients with SCMP
according to gender. Methods: One hundred and three patients diagnosed with
definite SCMP at a single tertiary institute from January 1997 to August 2014
were enrolled. SCMP was more common in women than in men. Results: Age at
presentation was not significantly different between the two groups (p = 0.758).
Preceding physical stress, especially acute medical illness, was more common in
male patients (p = 0.014), whereas emotional stress was more common in female
patients (p = 0.016). Severity of medical illness classified by the Acute
Physiology and Chronic Health Evaluation (APACHE) II score at the time of SCMP
diagnosis was not significantly different between men and women (p = 0.752).
Clinical characteristics, including symptoms, laboratory and electrocardiographic
findings, were similar. However, pump failure was more severe in men (p = 0.024).
Clinical outcomes were not statistically different (p = 0.220). Preceding
physical stress and lower left ventricular systolic function after 2 months were
independent risk factors for all-cause mortality for both genders. Women with an
APACHE II score >= 15 and men with reduced left ventricular ejection fraction
after 2 months had a greater risk of poor prognosis. Conclusion: SCMP was more
common in female patients. Female patients more commonly experienced preceding
emotional stress, whereas physical stress was more common in male patients.
Systolic dysfunction was more severe in men. Long-term clinical outcomes appeared
to be similar between men and women.
PMID- 29333216
TI - Salidroside Inhibits HMGB1 Acetylation and Release through Upregulation of SirT1
during Inflammation.
AB - HMGB1, a highly conserved nonhistone DNA-binding protein, plays an important role
in inflammatory diseases. Once released to the extracellular space, HMGB1 acts as
a proinflammatory cytokine that triggers inflammatory reaction. Our previous
study showed that salidroside exerts anti-inflammatory effect via inhibiting the
JAK2-STAT3 signalling pathway. However, whether salidroside inhibits the release
of HMGB1 is still unclear. In this study, we aim to study the effects of
salidroside on HMGB1 release and then investigate the potential molecular
mechanisms. In an experimental rat model of sepsis caused by CLP, salidroside
administration significantly attenuated lung injury and reduced the serum HMGB1
level. In RAW264.7 cells, we investigated the effects of salidroside on LPS
induced HMGB1 release and then explored the underlying molecular mechanisms. We
found that salidroside significantly inhibited LPS-induced HMGB1 release, and the
inhibitory effect was correlated with the HMGB1 acetylation levels. Mechanismly,
salidroside inhibits HMGB1 acetylation through the AMPK-SirT1 pathway. In
addition, SirT1 overexpression attenuated LPS-induced HMGB1 acetylation and
nucleocytoplasmic translocation. Furthermore, in SirT1 shRNA plasmid-transfected
cells, salidroside treatment enhanced SirT1 expression and reduced LPS-activated
HMGB1 acetylation and nucleocytoplasmic translocation. Collectively, these
results demonstrated that salidroside might reduce HMGB1 release through the AMPK
SirT1 signalling pathway and suppress HMGB1 acetylation and nucleocytoplasmic
translocation.
PMID- 29333218
TI - Impact of Mindfulness Based Stress Reduction Therapy on Myocardial Function and
Endothelial Dysfunction in Female Patients with Microvascular Angina.
AB - Background: Mindfulness-based stress reduction (MBSR) is a structured group
program that employs mindfulness meditation to alleviate suffering associated
with physical, psychosomatic, and psychiatric disorders. In this study, we
investigate the impact of MBSR on left ventricular (LV) and endothelial function
in female patients with microvascular angina. Methods: A total of 34 female
patients (mean age 52.2 +/- 13.8 years) diagnosed with microvascular angina
underwent a MBSR program with anti-anginal medication for 8 weeks. The global
longitudinal strain (GLS) of the LV was used as a parameter to assess myocardial
function and reactive brachial flow-mediated dilatation (FMD) was used to assess
endothelial function. Symptoms were analyzed by the Symptom Checklist 90 Revised
to determine emotional stress. Changes in GLS and FMD between baseline and post
MBSR were analyzed. Results: After 8 weeks of programmed MBSR treatment, stress
parameters were significantly decreased. In addition, GLS (-19.5 +/- 2.1% vs.
16.6 +/- 2.5%, p < 0.001) and reactive FMD significantly improved (8.9 +/- 3.0%
vs. 6.9 +/- 2.6%, p = 0.005) after MBSR compared to baseline. The changes in GLS
correlated to changes in FMD (r = 0.120, p = 0.340) and with the changes in most
stress parameters. Conclusion: MBSR has beneficial impacts on myocardial and
endothelial function in female patients with microvascular angina.
PMID- 29333213
TI - Chronic Kidney Disease and Disproportionally Increased Cardiovascular Damage:
Does Oxidative Stress Explain the Burden?
AB - Chronic kidney disease (CKD) patients are among the groups at the highest risk
for cardiovascular disease and significantly shortened remaining lifespan. CKD
enhances oxidative stress in the organism with ensuing cardiovascular damage.
Oxidative stress in uremia is the consequence of higher reactive oxygen species
(ROS) production, whereas attenuated clearance of pro-oxidant substances and
impaired antioxidant defenses play a complementary role. The pathophysiological
mechanism underlying the increased ROS production in CKD is at least partly
mediated by upregulation of the intrarenal angiotensin system. Enhanced oxidative
stress in the setting of the uremic milieu promotes enzymatic modification of
circulating lipids and lipoproteins, protein carbamylation, endothelial
dysfunction via disruption of nitric oxide (NO) pathways, and activation of
inflammation, thus accelerating atherosclerosis. Left ventricular hypertrophy
(LVH) and heart failure are hallmarks of CKD. NADPH oxidase activation, xanthine
oxidase, mitochondrial dysfunction, and NO-ROS are the main oxidative pathways
leading to LVH and the cardiorenal syndrome. Finally, a subset of antioxidant
enzymes, the paraoxonases (PON), deserves special attention due to abundant
clinical evidence accumulated regarding reduced serum PON1 activity in CKD as a
contributor to the increased burden of cardiovascular disease. Future,
meticulously designed studies are needed to assess the effects of antioxidant
therapy on patients with CKD.
PMID- 29333219
TI - Clinical Utility of Echocardiography for Early and Late Pulmonary Hypertension in
Preterm Infants: Relation with Bronchopulmonary Dysplasia.
AB - Background: We evaluated early and late pulmonary hypertension (PH) in preterm
infants and its relation with bronchopulmonary dysplasia (BPD). Methods: Sixty
seven preterm infants < 30 weeks' gestation underwent echocardiography within 14
days after birth for early PH and over 28 days after birth for late PH. We
measured tricuspid regurgitation (TR) peak velocity, pulse Doppler-derived
myocardial performance index (MPI) of right ventricle (RV) (RV MPI), eccentricity
index (EI), and tricuspid annular plane systolic excursion (TAPSE). Results: The
median gestation age of patients was 27 weeks (range, 23-30 weeks) and median
birth weight was 1030 g (range, 450-1780 g). TR peak velocity was measured only
in 19 patients (28.4%). Patients with symptomatic early PH (n = 11) showed a
significantly lower systolic EI and a significantly higher incidence of RV MPI >
0.38 and TAPSE < 0.5 cm than patients without PH. The incidence of symptomatic
early PH was highest in severe BPD, although this was not statistically
significant. Early echocardiographic parameters are not associated with BPD
development. Patients with severe BPD showed a significantly higher RV MPI and a
significantly higher incidence of RV MPI > 0.38 than patients with mild BPD, and
a significantly lower systolic EI and a significantly higher incidence of
systolic EI < 0.81 than patients without BPD. Conclusion: Systolic EI, RV MPI,
and TAPSE were well represented symptomatic early PH, while systolic EI and RV
MPI could be useful parameters for identifying late PH in preterm infants with
BPD, even if they did not present PH symptoms.
PMID- 29333221
TI - Horseshoe-like Shaped Atrial Septal Defects Confirmed on Three-Dimensional
Transesophageal Echocardiography.
PMID- 29333215
TI - Markers and Biomarkers of Endothelium: When Something Is Rotten in the State.
AB - Endothelium is a community of endothelial cells (ECs), which line the blood and
lymphatic vessels, thus forming an interface between the tissues and the blood or
lympha. This strategic position of endothelium infers its indispensable
functional role in controlling vasoregulation, haemostasis, and inflammation. The
state of endothelium is simultaneously the cause and effect of many diseases, and
this is coupled with modifications of endothelial phenotype represented by
markers and with biochemical profile of blood represented by biomarkers. In this
paper, we briefly review data on the functional role of endothelium, give
definitions of endothelial markers and biomarkers, touch on the methodological
approaches for revealing biomarkers, present an implicit role of endothelium in
some toxicological mechanistic studies, and survey the role of reactive oxygen
species (ROS) in modulation of endothelial status.
PMID- 29333220
TI - Outcomes of Left Ventricular Function According to Treatment Response for a
Patent Ductus Arteriosus in Preterm Infants.
AB - Background: To evaluate the outcomes of left ventricular (LV) function according
to treatment response for a hemodynamically significant patent ductus arteriosus
(hsPDA) in preterm infants. Methods: Echocardiograms of 21 preterm infants born
at gestational age < 31 weeks obtained at term-equivalent age were
retrospectively studied. Among preterm infants with a hsPDA, 9 underwent ligation
after failure of pharmacological closure (ligation group) and 6 experienced
successful pharmacological closure (medication group). Six preterm infants
without hsPDA (no-hsPDA group) were studied as controls. LV peak longitudinal
systolic strain (epsilon) of each infant was retrospectively obtained from
echocardiograms using velocity vector imaging, along with neonatal outcomes.
Results: Pharmacological closures were attempted at postnatal day 2-3. In the
ligation group, the median postnatal age at ligation was 20 days. In the ligation
group, LV peak longitudinal systolic epsilon was significantly decreased at term
equivalent age compared to the other groups. Between the medication and no-hsPDA
groups, LV peak longitudinal systolic epsilon did not differ significantly. Among
the neonatal outcomes, infants who experienced necrotizing enterocolitis (NEC)
showed significantly decreased LV peak longitudinal systolic epsilon compared to
the infants who did not experience NEC . Conclusion: We speculate that in preterm
infants with an hsPDA, in cases of medical treatment failure, early PDA ligation
at less than 20 days of postnatal age would be beneficial for preserving LV
systolic function.
PMID- 29333222
TI - Congenital Left Atrial Bands with Atrial Fibrillation.
PMID- 29333224
TI - PRDI-BF1 and PRDI-BF1P isoform expressions correlate with disease status in
multiple myeloma patients.
PMID- 29333223
TI - Development of practical functional electrical stimulation cycling systems based
on an electromyography study of the Cybathlon 2016.
AB - The purpose of this study was to develop a functional electrical stimulation
(FES) system based on the motor driving concept for use by spinal cord injury
patients participating in the FES Cycling competition at the Cybathlon 2016. The
proposed FES system consists of a low-power control system, a precise processor
unit, and a 4-channel stimulation unit. Self-adhesive carbon conductive
electrodes were utilized for stimulation. A 26-year-old SCI patient was qualified
to participate in the competition. The pilot patient underwent training for 16
months, which included experience with FES stimulation, performing FES cycling,
and reducing spasticity, to practice using the FES system. In addition, using
surface electromyography (EMG) during cycling, the muscle activation pattern for
generating the stimulation profile was applied and resulted in good performance.
The best FES cycling performance the pilot achieved was 1000 meters translation
with the cycling system during twelve minutes of using the FES system. The pilot
achieved an 1000 meters translation mobility within an average of 16 minutes of
cycling. Nevertheless, the system must be further investigated regarding muscle
fatigue and other factors that may affect the stimulation conditions.
PMID- 29333225
TI - A rare cause of pericardial effusion and ascites: POEMS syndrome.
PMID- 29333226
TI - Expression of some ATP-binding cassette transporters in acute myeloid leukemia.
PMID- 29333227
TI - Dasatinib-induced hemorrhagic colitis complicated with cytomegalovirus infection.
PMID- 29333228
TI - Quantification of polysaccharides fixed to Gram stained slides using lactophenol
cotton blue and digital image processing.
AB - I discovered indigo rings and circles in Escherichia coli ATCC(r) 25922TM
cultures when I added the non-specific polysaccharide stain lactophenol cotton
blue to Gram stained slides sampled from 96-well plates used to measure
quantitative growth kinetics (QGK) in virtual colony count antimicrobial assays.
I attribute the dark blue staining to the presence of capsular polysaccharides
and bacterial slime associated with clumps of cells. Since all bacterial cells
are glycosylated, the majority of cells stain light blue. The contrast between
dark and light staining is sufficient to enable a digital image processing
thresholding technique to be quantitative for circular or ring-shaped structures
that imply the presence of slime fixed to the glass. These polysaccharides
indicate a possible mechanism of resistance to antimicrobial peptides such as
defensins, lectins with high affinity for polysaccharides and glycosylated
proteins. Adding lactophenol cotton blue to Gram stained slides is a quick and
inexpensive way to screen cell cultures for bacterial slime, clumps and biofilms,
revealing details of polysaccharide secretion that are missed using the Gram
stain alone. Combined with QGK threshold times, the lactophenol cotton blue Gram
stain followed by digital image processing provides quantitative information
useful for quality control, environmental monitoring and detection of clumping
environmental factors.
PMID- 29333229
TI - Predicted protein interactions of IFITMs which inhibit Zika virus infection.
AB - After the first reported case of Zika virus in Brazil, in 2015, a significant
increase in the reported cases of microcephaly was observed. Microcephaly is a
neurological condition in which the infant's head is significantly smaller with
complications in brain development. Recently, two small membrane-associated
interferon-inducible transmembrane proteins (IFITM1 and IFITM3) have been shown
to repress members of the flaviviridae family which includes the Zika virus.
However, the exact mechanisms leading to the inhibition of the virus are yet
unknown. Here, we assembled an interactome of IFITM1 and IFITM3 with known
protein-protein interactions (PPIs) collected from publicly available databases
and novel PPIs predicted using High-confidence Protein-Protein Interaction
Prediction (HiPPIP) model. We analyzed the functional and pathway associations of
the interacting proteins, and found that there are several immunity pathways
(interferon signaling, cd28 signaling in T-helper cells crosstalk between
dendritic cells and natural killer cells), neuronal pathways (axonal guidance
signaling, neural tube closure and actin cytoskeleton signaling) and
developmental pathways that are associated with these interactors. These results
could help direct future research in elucidating the mechanisms underlying the
viral immunity to Zika virus and other flaviviruses.
PMID- 29333230
TI - Funding knowledgebases: Towards a sustainable funding model for the UniProt use
case.
AB - Millions of life scientists across the world rely on bioinformatics data
resources for their research projects. Data resources can be very expensive,
especially those with a high added value as the expert-curated knowledgebases.
Despite the increasing need for such highly accurate and reliable sources of
scientific information, most of them do not have secured funding over the near
future and often depend on short-term grants that are much shorter than their
planning horizon. Additionally, they are often evaluated as research projects
rather than as research infrastructure components. In this work, twelve funding
models for data resources are described and applied on the case study of the
Universal Protein Resource (UniProt), a key resource for protein sequences and
functional information knowledge. We show that most of the models present
inconsistencies with open access or equity policies, and that while some models
do not allow to cover the total costs, they could potentially be used as a
complementary income source. We propose the Infrastructure Model as a sustainable
and equitable model for all core data resources in the life sciences. With this
model, funding agencies would set aside a fixed percentage of their research
grant volumes, which would subsequently be redistributed to core data resources
according to well-defined selection criteria. This model, compatible with the
principles of open science, is in agreement with several international
initiatives such as the Human Frontiers Science Program Organisation (HFSPO) and
the OECD Global Science Forum (GSF) project. Here, we have estimated that less
than 1% of the total amount dedicated to research grants in the life sciences
would be sufficient to cover the costs of the core data resources worldwide,
including both knowledgebases and deposition databases.
PMID- 29333231
TI - Using bio.tools to generate and annotate workbench tool descriptions.
AB - Workbench and workflow systems such as Galaxy, Taverna, Chipster, or Common
Workflow Language (CWL)-based frameworks, facilitate the access to bioinformatics
tools in a user-friendly, scalable and reproducible way. Still, the integration
of tools in such environments remains a cumbersome, time consuming and error
prone process. A major consequence is the incomplete or outdated description of
tools that are often missing important information, including parameters and
metadata such as publication or links to documentation. ToolDog (Tool DescriptiOn
Generator) facilitates the integration of tools - which have been registered in
the ELIXIR tools registry (https://bio.tools) - into workbench environments by
generating tool description templates. ToolDog includes two modules. The first
module analyses the source code of the bioinformatics software with language
specific plugins, and generates a skeleton for a Galaxy XML or CWL tool
description. The second module is dedicated to the enrichment of the generated
tool description, using metadata provided by bio.tools. This last module can also
be used on its own to complete or correct existing tool descriptions with missing
metadata.
PMID- 29333232
TI - Highlights of the second ISCB Student Council Symposium in Africa, 2017.
AB - Student Council Symposiums (SCSs) have been found to be very useful for students
and young researchers. This is especially true given that the events are held
directly before large international conferences, giving attendees a chance to
gain exposure and have a warm up to the social nuances involved in attending such
a meeting. This was the second SCS held in Africa in conjunction with the
International Society for Computational Biology (ISCB) and the African Society
for Bioinformatics and Computational Biology's (ASBCB) biennial meeting. This
symposium was organised by students within the society inside Africa and was held
on the 10 th of October 2017 in Entebbe, Uganda.
PMID- 29333233
TI - On the primacy and irreducible nature of first-person versus third-person
information.
AB - In this essay, we will support the claim that a) some first-person accounts
cannot be reduced to their third-person neural and psychophysiological correlates
and b) that these first-person accounts are the only information to reckon when
it is necessary to analyse qualia contents. Consequently, for many phenomena,
first-person accounts are the only reliable source of information available and
the knowledge of their neural and psychophysical correlates don't offer any
additional information about them.
PMID- 29333234
TI - Case Report: Laparoscopic hepatectomy in an elderly patient with major
comorbidities.
AB - Surgeons have been hesitant to proceed to hepatectomy in elderly patients, due to
the higher rate of comorbidities and the reduced reserves. An 81-year-old male
with hepatocellular carcinoma in the segment VI of the liver and several major
cardiovascular, pulmonary and metabolic comorbid illnesses was referred to our
department for treatment. He underwent transarterial chemoembolization of the
liver tumor and afterwards he underwent laparoscopic resection of the hepatic
segment VI, with an uneventful postoperative course. This case indicates the
safety and feasibility of laparoscopic liver resections in older patients, even
when major comorbidities are present, provided that there is a careful planning
of therapeutic strategy and operation.
PMID- 29333235
TI - Case Report: Synchronous primary malignancy including the breast and endometrium.
AB - Breast and endometrial cancer are the most common types of female cancers, but
the incidence of both of these malignancies in a single patient is a rare event.
Multiple primary malignancy has been increasingly reported over the past decade,
and double primary cancer is considered as the most common type. In this study,
we present a 53-year-old woman with synchronous primary malignancy of breast and
endometrium. This patient had a history of breast and endometrial cancer in her
family. Mammography and chest CT of the patient revealed a mass in the right
breast and left supraclavicular region. However, the patient did not want to
initiate treatment. Subsequently, the patient returned with a chief complaint of
persistent abnormal vaginal bleeding. Abdominopelvic CT scan of the patient
revealed a huge soft tissue mass in the pelvic cavity. She underwent
hysterectomy, and pathology revealed endometrioid carcinoma, which had invaded
the full thickness of uterine wall. Since this type of malignancy is rare and
several risk factors are associated with it, it is worth being considered by
clinicians when making decisions about screening or strategy for prevention.
PMID- 29333237
TI - Draft genome of tule elk Cervus elaphus nannodes.
AB - This paper presents the first draft genome of the tule elk ( Cervus elaphus
nannodes), a subspecies native to California that underwent an extreme genetic
bottleneck in the late 1800s. The genome was generated from Illumina HiSeq 3000
whole genome sequencing of four individuals, resulting in the assembly of 2.395
billion base pairs (Gbp) over 602,862 contigs over 500 bp and N50 = 6,885 bp.
This genome provides a resource to facilitate future genomic research on elk and
other cervids.
PMID- 29333236
TI - In silico analysis of natural compounds targeting structural and nonstructural
proteins of chikungunya virus.
AB - Background: Chikungunya fever presents as a high-grade fever during its acute
febrile phase and can be prolonged for months as chronic arthritis in affected
individuals. Currently, there are no effective drugs or vaccines against this
virus. The present study was undertaken to evaluate protein-ligand interactions
of all chikungunya virus (CHIKV) proteins with natural compounds from a MolBase
library in order to identify potential inhibitors of CHIKV. Methods: Virtual
screening of the natural compound library against four non-structural and five
structural proteins of CHIKV was performed. Homology models of the viral proteins
with unknown structures were created and energy minimized by molecular dynamic
simulations. Molecular docking was performed to identify the potential inhibitors
for CHIKV. The absorption, distribution, metabolism and excretion (ADME) toxicity
parameters for the potential inhibitors were predicted for further prioritization
of the compounds. Results: Our analysis predicted three compounds, Catechin-5-O
gallate, Rosmarinic acid and Arjungenin, to interact with CHIKV proteins; two
(Catechin-5-O-gallate and Rosmarinic acid) with capsid protein, and one
(Arjungenin) with the E3. Conclusion: The compounds identified show promise as
potential antivirals, but further in vitro studies are required to test their
efficacy against CHIKV.
PMID- 29333238
TI - A method to estimate the number of neurons supporting visual orientation
discrimination in primates.
AB - In this method article, we show how to estimate of the number of retinal ganglion
cells (RGC), and the number of lateral genicular nucleus (LGN) and primary visual
cortex (V1) neurons involved in visual orientation discrimination tasks. We
reported the results of this calculation in Kanitscheider et al. (2015), where we
were interested in comparing the number of neurons in the visual periphery versus
visual cortex for a specific experiment. This calculation allows estimation of
the information content at different stages of the visual pathway, which can be
used to assess the efficiency of the computations performed. As these numbers are
generally not readily available but may be useful to other researchers, we
explain here in detail how we obtained them. The calculation is straightforward,
and simply requires combining anatomical and physiological information about the
macaque visual pathway. Similar information could be used to repeat the
calculation for other species or modalities.
PMID- 29333239
TI - The peer review process for awarding funds to international science research
consortia: a qualitative developmental evaluation.
AB - Background: Evaluating applications for multi-national, multi-disciplinary, dual
purpose research consortia is highly complex. There has been little research on
the peer review process for evaluating grant applications and almost none on how
applications for multi-national consortia are reviewed. Overseas development
investments are increasingly being channelled into international science
consortia to generate high-quality research while simultaneously strengthening
multi-disciplinary research capacity. We need a better understanding of how such
decisions are made and their effectiveness. Methods: An award-making institution
planned to fund 10 UK-Africa research consortia. Over two annual rounds, 34 out
of 78 eligible applications were shortlisted and reviewed by at least five
external reviewers before final selections were made by a face-to-face panel. We
used an innovative approach involving structured, overt observations of award
making panel meetings and semi-structured interviews with panel members to
explore how assessment criteria concerning research quality and capacity
strengthening were applied during the peer review process. Data were coded and
analysed using pre-designed matrices which incorporated categories relating to
the assessment criteria. Results: In general the process was rigorous and well
managed. However, lack of clarity about differential weighting of criteria and
variations in the panel's understanding of research capacity strengthening
resulted in some inconsistencies in use of the assessment criteria. Using the
same panel for both rounds had advantages, in that during the second round
consensus was achieved more quickly and the panel had increased focus on
development aspects. Conclusion: Grant assessment panels for such complex
research applications need to have topic- and context-specific expertise. They
must also understand research capacity issues and have a flexible but equitable
and transparent approach. This study has developed and tested an approach for
evaluating the operation of such panels and has generated lessons that can
promote coherence and transparency among grant-makers and ultimately make the
award-making process more effective.
PMID- 29333240
TI - The use of dexmedetomidine and intravenous acetaminophen for the prevention of
postoperative delirium in cardiac surgery patients over 60 years of age: a pilot
study.
AB - Background: Delirium is associated with many negative health outcomes.
Postoperative sedation and opioid administration may contribute to delirium. We
hypothesize that the use of dexmedetomidine and Intravenous acetaminophen (IVA)
may lead to reduced opioid consumption and decreased incidence of postoperative
delirium. This pilot study aims to assess feasibility of using dexmedetomidine
and IVA in cardiac surgical patients, and obtain effect size estimates for
incidence and duration of delirium. Methods: A total of 12 adult patients >60
years of age undergoing cardiac surgery were recruited for the study after IRB
approval and randomized into 4 groups: Propofol only (P), Propofol with IVA
(P+A), Dexmedetomidine only (D), Dexmedetomidine with IVA (D+A). Preoperative
baseline cognition and postoperative delirium was assessed daily until discharge.
The feasibility was assessed by the number of patients who successfully completed
the study. Results: All patients completed the study protocol successfully. The
total incidence of delirium in the study population was 42% (5/12): 67% (2/3) in
the group P, and 67% (2/3) in the group D, 33% (1/3) in D+A group and 0%(0/3)
P+A group. The incidence of delirium was 17% (1/6) in the group receiving IVA
compared to 67% (4/6) that did not receive IVA. The mean duration of delirium was
0-1 days. One patient expired after surgery, unrelated to the study protocol. One
patient in the D group experienced hypotension with systolic blood pressure <90
mm of Hg. Conclusions: The feasibility of performing a large-scale project is
ascertained by the study. Patients receiving IVA had lower incidence of delirium
compared to patients not receiving IVA which suggests that IVA may have a role in
reducing the incidence of delirium. A prospective randomized, placebo-controlled
trial will be the next step in investigating the role of dexmedetomidine and IVA
in reducing the incidence of delirium.
PMID- 29333241
TI - Developing data interoperability using standards: A wheat community use case.
AB - In this article, we present a joint effort of the wheat research community, along
with data and ontology experts, to develop wheat data interoperability
guidelines. Interoperability is the ability of two or more systems and devices to
cooperate and exchange data, and interpret that shared information.
Interoperability is a growing concern to the wheat scientific community, and
agriculture in general, as the need to interpret the deluge of data obtained
through high-throughput technologies grows. Agreeing on common data formats,
metadata, and vocabulary standards is an important step to obtain the required
data interoperability level in order to add value by encouraging data sharing,
and subsequently facilitate the extraction of new information from existing and
new datasets. During a period of more than 18 months, the RDA Wheat Data
Interoperability Working Group (WDI-WG) surveyed the wheat research community
about the use of data standards, then discussed and selected a set of
recommendations based on consensual criteria. The recommendations promote
standards for data types identified by the wheat research community as the most
important for the coming years: nucleotide sequence variants, genome annotations,
phenotypes, germplasm data, gene expression experiments, and physical maps. For
each of these data types, the guidelines recommend best practices in terms of use
of data formats, metadata standards and ontologies. In addition to the best
practices, the guidelines provide examples of tools and implementations that are
likely to facilitate the adoption of the recommendations. To maximize the
adoption of the recommendations, the WDI-WG used a community-driven approach that
involved the wheat research community from the start, took into account their
needs and practices, and provided them with a framework to keep the
recommendations up to date. We also report this approach's potential to be
generalizable to other (agricultural) domains.
PMID- 29333243
TI - Unexpected results in Chernozem soil respiration while measuring the effect of a
bio-fertilizer on soil microbial activity.
AB - The number of studies investigating the effect of bio-fertilizers is increasing
because of their importance in sustainable agriculture and environmental quality.
In our experiments, we measured the effect of different fertilizers on soil
respiration. In the present study, we were looking for the cause of unexpected
changes in CO2 values while examining Chernozem soil samples. We concluded that
CO2 oxidizing microbes or methanotrophs may be present in the soil that
periodically consume CO2 . This is unusual for a sample taken from the upper
layer of well-ventilated Chernozem soil with optimal moisture content.
PMID- 29333242
TI - Predictive value of early postoperative IOP and bleb morphology in Mitomycin-C
augmented trabeculectomy.
AB - Background: Our aim was to determine the predictive value of postoperative bleb
morphological features and intraocular pressure (IOP) on the success rate of
trabeculectomy. Methods: In this prospective interventional case series, we
analyzed for one year 80 consecutive primary open angle glaucoma patients who
underwent mitomycin-augmented trabeculectomy. Bleb morphology was scored using
the Indiana bleb appearance grading scale (IBAGS). Success was defined as IOP
<=15 mmHg with or without medications at 12 months. We tested for IOP and bleb
morphological differences between groups, applied a multivariable regression
analysis and determined the area under the receiver operating characteristic
curve (AUC). Results: Age and gender were equally distributed (62.3+/-13.1 years,
P=0.911). IOP of patients with a successful outcome did not differ from
unsuccessful ones on day 1, 7 and 30 (all P>=0.2). The AUC of IOP at day 1, day 7
and 30 for predicting a successful outcome was 0.355, 0.452, and 0.80,
respectively. The AUC for bleb morphology parameters, bleb height, extension, and
vascularization, on day 14 were 0.368, 0.408, and 0.549, respectively. Values for
day 30 were 0.428, 0.563, and 0.654. IOP change from day 1 to day 30 was a good
predictor of failure (AUC=0.838, 95% CI: 0.704 to 0.971) with a change of more
than 3 mmHg predicting failure with a sensitivity of 82.5% (95% CI: 68 to 91%)
and a specificity of 87.5% (95% CI: 53 to 98%). Conclusions: The postoperative
IOP on day 30 had a fair to good accuracy while the bleb features failed to
predict a successful outcome. An IOP increase by as little as more than 3 mmHg
during the first 30 days was a good predictor of failure.
PMID- 29333244
TI - Piscine birnavirus triggers antiviral immune response in trout red blood cells,
despite not being infective.
AB - Background: Some fish viruses, such as piscine orthoreovirus and infectious
salmon anemia virus, target red blood cells (RBCs), highly replicate inside them
and induce an immune response. However, the implications of RBCs in the context
of birnavirus infection (i.e, infectious pancreatic necrosis virus (IPNV)) have
not yet been studied. Methods:Ex vivo trout RBCs were obtained from peripheral
blood, ficoll purified and exposed to IPNV in order to analyze infectivity and
induced immune response using RT-qPCR, immune fluorescence imaging, flow
cytometry and western-blotting techniques. Results: IPNV could not infect RBCs;
however, IPNV-exposed RBCs increased the expression of the INF1-related genes ifn
1, pkr and mx genes. Moreover, conditioned media from IPNV-exposed RBCs conferred
protection against IPNV infection in CHSE-214 fish cell line. Conclusions: Trout
RBCs could trigger an antiviral immune response against IPNV infection despite
not being infected. Fish RBCs could be considered mediators of the antiviral
response and therefore targets of novel DNA vaccines and new strategies against
fish viral infections. Further research is ongoing to completely understand the
molecular mechanism that triggers this immune response in trout RBCs.
PMID- 29333245
TI - The impact of fresh gas flow on wash-in, wash-out time and gas consumption for
sevoflurane and desflurane, comparing two anaesthesia machines, a test-lung
study.
AB - Low-flow anaesthesia is considered beneficial for the patient and the
environment, and it is cost reducing due to reduced anaesthetic gas consumption.
An initial high-flow to saturate the circle system ( wash-in) is desirable from a
clinical point of view. We measured the wash-in and wash-out times (time to
saturate and to eliminate the anaesthetic agent, AA), for sevoflurane and
desflurane, in a test-lung with fixed 3 MAC vaporizer setting at different fresh
gas flow (FGF) and calculated the consumption of AA. We tried to find an optimal
flow rate for speed and gas consumption, comparing two anaesthesia machines
(AMs): Aisys and Flow-i. Time to reach 1 minimal alveolar concentration (MAC)
(wash-in) decreased (p<0.05) at higher flow rates (1 - 2 - 4) but plateaued at 4
4.8 l/min. The consumption of AA was at its lowest around 4-4.8 l/min (optimal
flow) for all but the Aisys /desflurane group. Wash-out times decreased as FGF
increased, until reaching plateau at FGF of 4-6 l/min. Aisys had generally
shorter wash-in times at flow rates < 4 l/min as well as lower consumption of AA.
At higher flow rates there were little difference between the AMs. The "optimal
FGF" for wash-out, elimination of gas from the test-lung and circle system,
plateaued with no increase in speed beyond 6 l/min. A fresh gas flow of 4 l/min.
seems "optimal" taking speed to reach a 1 MAC ET and gas consumption into account
during wash-in with a fixed 3 MAC vaporizer setting, and increasing fresh gas
flow beyond 6 l/min does not seem to confirm major benefit during wash-out.
PMID- 29333246
TI - Easy and efficient ensemble gene set testing with EGSEA.
AB - Gene set enrichment analysis is a popular approach for prioritising the
biological processes perturbed in genomic datasets. The Bioconductor project
hosts over 80 software packages capable of gene set analysis. Most of these
packages search for enriched signatures amongst differentially regulated genes to
reveal higher level biological themes that may be missed when focusing only on
evidence from individual genes. With so many different methods on offer, choosing
the best algorithm and visualization approach can be challenging. The EGSEA
package solves this problem by combining results from up to 12 prominent gene set
testing algorithms to obtain a consensus ranking of biologically relevant
results.This workflow demonstrates how EGSEA can extend limma-based differential
expression analyses for RNA-seq and microarray data using experiments that
profile 3 distinct cell populations important for studying the origins of breast
cancer. Following data normalization and set-up of an appropriate linear model
for differential expression analysis, EGSEA builds gene signature specific
indexes that link a wide range of mouse or human gene set collections obtained
from MSigDB, GeneSetDB and KEGG to the gene expression data being investigated.
EGSEA is then configured and the ensemble enrichment analysis run, returning an
object that can be queried using several S4 methods for ranking gene sets and
visualizing results via heatmaps, KEGG pathway views, GO graphs, scatter plots
and bar plots. Finally, an HTML report that combines these displays can fast
track the sharing of results with collaborators, and thus expedite downstream
biological validation. EGSEA is simple to use and can be easily integrated with
existing gene expression analysis pipelines for both human and mouse data.
PMID- 29333247
TI - Differential methylation analysis of reduced representation bisulfite sequencing
experiments using edgeR.
AB - Studies in epigenetics have shown that DNA methylation is a key factor in
regulating gene expression. Aberrant DNA methylation is often associated with DNA
instability, which could lead to development of diseases such as cancer. DNA
methylation typically occurs in CpG context. When located in a gene promoter, DNA
methylation often acts to repress transcription and gene expression. The most
commonly used technology of studying DNA methylation is bisulfite sequencing (BS
seq), which can be used to measure genomewide methylation levels on the single
nucleotide scale. Notably, BS-seq can also be combined with enrichment
strategies, such as reduced representation bisulfite sequencing (RRBS), to target
CpG-rich regions in order to save per-sample costs. A typical DNA methylation
analysis involves identifying differentially methylated regions (DMRs) between
different experimental conditions. Many statistical methods have been developed
for finding DMRs in BS-seq data. In this workflow, we propose a novel approach of
detecting DMRs using edgeR. By providing a complete analysis of RRBS profiles of
epithelial populations in the mouse mammary gland, we will demonstrate that
differential methylation analyses can be fit into the existing pipelines
specifically designed for RNA-seq differential expression studies. In addition,
the edgeR generalized linear model framework offers great flexibilities for
complex experimental design, while still accounting for the biological
variability. The analysis approach illustrated in this article can be applied to
any BS-seq data that includes some replication, but it is especially appropriate
for RRBS data with small numbers of biological replicates.
PMID- 29333248
TI - Out-of-pocket health expenditure and fairness in utilization of health care
facilities in Cambodia in 2005 and 2010.
AB - Background: Out-of-pocket (OOP) payments for health care are highly pervasive in
several low-and-middle income countries. The Cambodian health system has
envisaged massive repositioning of various health care financing to ensure
equitable access to health care. This analysis examines catastrophic, economic,
as well as fairness, impacts of OOP health care payments on households in
Cambodia over time. Methods: Data from two waves of a nationally representative
household survey conducted in Cambodia (CDHS Surveys 2005 and 2010) were
utilized. Healthcare utilizations based on economic status were compared during
2005 and 2010. Variables of interests were i) where care was sought and the
instances of treatments, i.e. was treatment sought the first, second or third
time; (ii) the mode of payment for treatment of the respondent or for any
household member due to sickness or injury in the last 30 days prior to the
survey period. Lorenz curves were applied to assess the degree of distribution of
inequality in OOP expenditures between different income brackets. Results: The
findings revealed that there was inequality and unfairness in health care
payments, and catastrophic spending is more common among the poor in Cambodia.
The majority of people from poorer households experienced economic hardship and
have taken to catastrophic health care spending through sales of personal
possessions. Conclusion: Based on the findings from this analysis, more
attention is needed on effective financial protection for Cambodians to promote
fairness. The government should increase spending on services being provided at
public health care facilities to reduce ever increasing reliance on private
sector providers. These approaches would go a long way to reduce the economic
burden of care utilization among the poorest.
PMID- 29333249
TI - Health Technology Assessment capacity development in low- and middle-income
countries: Experiences from the international units of HITAP and NICE.
AB - Health Technology Assessment (HTA) is policy research that aims to inform
priority setting and resource allocation. HTA is increasingly recognized as a
useful policy tool in low- and middle-income countries (LMICs), where there is a
substantial need for evidence to guide Universal Health Coverage policies, such
as benefit coverage, quality improvement interventions and quality standards, all
of which aim at improving the efficiency and equity of the healthcare system. The
Health Intervention and Technology Assessment Program (HITAP), Thailand, and the
National Institute for Health and Care Excellence (NICE), UK, are national HTA
organizations providing technical support to governments in LMICs to build up
their priority setting capacity. This paper draws lessons from their capacity
building programs in India, Colombia, Myanmar, the Philippines, and Vietnam. Such
experiences suggest that it is not only technical capacity, for example
analytical techniques for conducting economic evaluation, but also management,
coordination and communication capacity that support the generation and use of
HTA evidence in the respective settings. The learned lessons may help guide the
development of HTA capacity in other LMICs.
PMID- 29333250
TI - Retract p < 0.005 and propose using JASP, instead.
AB - Seeking to address the lack of research reproducibility in science, including
psychology and the life sciences, a pragmatic solution has been raised recently:
to use a stricter p < 0.005 standard for statistical significance when claiming
evidence of new discoveries. Notwithstanding its potential impact, the proposal
has motivated a large mass of authors to dispute it from different philosophical
and methodological angles. This article reflects on the original argument and the
consequent counterarguments, and concludes with a simpler and better-suited
alternative that the authors of the proposal knew about and, perhaps, should have
made from their Jeffresian perspective: to use a Bayes factors analysis in
parallel (e.g., via JASP) in order to learn more about frequentist error
statistics and about Bayesian prior and posterior beliefs without having to mix
inconsistent research philosophies.
PMID- 29333251
TI - Can circulating tumor DNA be used for direct and early stage cancer detection?
AB - In the August 16th issue of Science Translational Medicine, Phallen et al propose
a method for early cancer diagnosis by using circulating tumor DNA (1). One major
advance of this paper includes optimized sequencing of cell-free/circulating
tumor DNA (ctDNA) without knowledge of tumor mutations. Evaluation of 200
patients with colorectal, breast, lung and ovarian cancer revealed mutations in
ctDNA in approx. 60-70% of all patients, including stage 1 and stage 2 disease.
If this data can be reproduced in asymptomatic individuals, they will likely have
a major impact on early cancer detection and patient outcomes. In this
commentary, we examine the feasibility of this approach for detecting small,
asymptomatic tumors, based on previously published empirical data.
PMID- 29333252
TI - Recent advances in pharmacological management of urinary incontinence.
AB - Lower urinary tract symptoms-in particular, storage disorders (for example,
urinary incontinence) as well as bladder underactivity-are major health-related
problems that increase with age. Yet lower urinary tract symptoms remain under
diagnosed and poorly managed, and incontinence has been cited as the major reason
for institutionalization in elderly populations and is one of the most common
conditions in primary care practice. Although lifestyle and behavior therapy has
been used as a useful treatment regimen for urge incontinence, medications (often
used as adjunct) can provide additional benefit. This review will include current
therapies used for treatment of urinary incontinence.
PMID- 29333253
TI - The stress concept in gastroenterology: from Selye to today.
AB - More than eighty years after Hans Selye (1907-1982) first developed a concept
describing how different types of environmental stressors affect physiological
functions and promote disease development (called the "general adaptation
syndrome") in 1936, we herein review advances in theoretical, mechanistic, and
clinical knowledge in stress research, especially in the area of
gastroenterology, and summarize progress and future perspectives arising from an
interdisciplinary psychoneurobiological framework in which genetics, epigenetics,
and other advanced ( omics) technologies in the last decade continue to refine
knowledge about how stress affects the brain-gut axis in health and
gastrointestinal disease. We demonstrate that neurobiological stress research
continues to be a driving force for scientific progress in gastroenterology and
related clinical areas, inspiring translational research from animal models to
clinical applications, while highlighting some areas that remain incompletely
understood, such as the roles of sex/gender and gut microbiota in health and
disease. Future directions of research should include not only the genetics of
the stress response and resilience but also epigenetic contributions.
PMID- 29333254
TI - Better understanding of childhood asthma, towards primary prevention - are we
there yet? Consideration of pertinent literature.
AB - Asthma is a chronic disease, characterized by reversible airway obstruction,
airway inflammation and hyper-reactivity. The prevalence of asthma has risen
dramatically over the past decade, affecting around 300,000,000 people. The
etiology is multifactorial, with genetic, epigenetic, developmental and
environmental factors playing a role. A complex interaction between the
intrauterine environment, the developing immune system, the infant's microbiome
and infectious organisms may lead to the development of allergic sensitization
and asthma. Thus, a large number of studies have investigated the risk factors
for childhood asthma, with a meticulous search of modifiable factors that could
aid in primary prevention. We present a current literature review from 2014-2017,
as well as older classic publications, on the pathogenesis and the potential
modifiable factors for primary prevention of asthma. No ideal preventive measure
has yet been found. Rather, creating favorable prenatal and postnatal
environments, minimal exposure to hostile environmental factors, prevention of
infections in early life, allergic desensitization and nutritional modifications
could possibly reduce asthma inception. In the era of personalized medicine,
identifying individual risk factors and tailoring specific preventive measures is
warranted.
PMID- 29333256
TI - Pathophysiology and treatment of patients with beta-thalassemia - an update.
AB - Thalassemia (thal) is an autosomal recessive, hereditary, chronic hemolytic
anemia due to a partial or complete deficiency in the synthesis of alpha-globin
chains (alpha-thal) or beta-globin chains (beta-thal) that compose the major
adult hemoglobin (alpha 2beta 2). It is caused by one or more mutations in the
corresponding genes. The unpaired globin chains are unstable; they precipitate
intracellularly, resulting in hemolysis, premature destruction of red blood cell
[RBC] precursors in the bone marrow, and a short life-span of mature RBCs in the
circulation. The state of anemia is treated by frequent RBC transfusions. This
therapy results in the accumulation of iron (iron overload), a condition that is
exacerbated by the breakdown products of hemoglobin (heme and iron) and the
increased iron uptake for the chronic accelerated, but ineffective, RBC
production. Iron catalyzes the generation of reactive oxygen species, which in
excess are toxic, causing damage to vital organs such as the heart and liver and
the endocrine system. Herein, we review recent findings regarding the
pathophysiology underlying the major symptoms of beta-thal and potential
therapeutic modalities for the amelioration of its complications, as well as new
modalities that may provide a cure for the disease.
PMID- 29333257
TI - Recent advances on gradient hydrogels in biomimetic cartilage tissue engineering.
AB - Articular cartilage (AC) is a seemingly simple tissue that has only one type of
constituting cell and no blood vessels and nerves. In the early days of tissue
engineering, cartilage appeared to be an easy and promising target for
reconstruction and this was especially motivating because of widespread AC
pathologies such as osteoarthritis and frequent sports-induced injuries. However,
AC has proven to be anything but simple. Recreating the varying properties of its
zonal structure is a challenge that has not yet been fully answered. This caused
the shift in tissue engineering strategies toward bioinspired or biomimetic
approaches that attempt to mimic and simulate as much as possible the structure
and function of the native tissues. Hydrogels, particularly gradient hydrogels,
have shown great potential as components of the biomimetic engineering of the
cartilaginous tissue.
PMID- 29333255
TI - In vivo genome editing in animals using AAV-CRISPR system: applications to
translational research of human disease.
AB - Adeno-associated virus (AAV) has shown promising therapeutic efficacy with a good
safety profile in a wide range of animal models and human clinical trials. With
the advent of clustered regulatory interspaced short palindromic repeat (CRISPR)
based genome-editing technologies, AAV provides one of the most suitable viral
vectors to package, deliver, and express CRISPR components for targeted gene
editing. Recent discoveries of smaller Cas9 orthologues have enabled the
packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery
vehicle for robust in vivo genome editing. Here, we discuss how the combined use
of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and
different routes of administration has advanced the development of efficient and
precise in vivo genome editing and comprehensively review the various AAV-CRISPR
systems that have been effectively used in animals. We then discuss the clinical
implications and potential strategies to overcome off-target effects,
immunogenicity, and toxicity associated with CRISPR components and AAV delivery
vehicles. Finally, we discuss ongoing non-viral-based ex vivo gene therapy
clinical trials to underscore the current challenges and future prospects of
CRISPR/Cas9 delivery for human therapeutics.
PMID- 29333258
TI - An RNA decay factor wears a new coat: UPF3B modulates translation termination.
AB - Nonsense-mediated RNA decay (NMD) is a highly conserved and selective RNA
turnover pathway that has been subject to intense scrutiny. NMD identifies and
degrades subsets of normal RNAs, as well as abnormal mRNAs containing premature
termination codons. A core factor in this pathway-UPF3B-is an adaptor protein
that serves as an NMD amplifier and an NMD branch-specific factor. UPF3B is
encoded by an X-linked gene that when mutated causes intellectual disability and
is associated with neurodevelopmental disorders, including schizophrenia and
autism. Neu-Yilik et al. now report a new function for UPF3B: it modulates
translation termination. Using a fully reconstituted in vitro translation system,
they find that UPF3B has two roles in translation termination. First, UPF3B
delays translation termination under conditions that mimic premature translation
termination. This could drive more efficient RNA decay by allowing more time for
the formation of RNA decay-stimulating complexes. Second, UPF3B promotes the
dissociation of post-termination ribosomal complexes that lack nascent peptide.
This implies that UPF3B could promote ribosome recycling. Importantly, the
authors found that UPF3B directly interacts with both RNA and the factors that
recognize stop codons-eukaryotic release factors (eRFs)-suggesting that UPF3B
serves as a direct regulator of translation termination. In contrast, a NMD
factor previously thought to have a central regulatory role in translation
termination-the RNA helicase UPF1-was found to indirectly interact with eRFs and
appears to act exclusively in post-translation termination events, such as RNA
decay, at least in vitro. The finding that an RNA decay-promoting factor, UFP3B,
modulates translation termination has many implications. For example, the ability
of UPF3B to influence the development and function of the central nervous system
may be not only through its ability to degrade specific RNAs but also through its
impact on translation termination and subsequent events, such as ribosome
recycling.
PMID- 29333259
TI - Predictors of outcome in phaeochromocytomas and paragangliomas.
AB - Phaeochromocytomas and paragangliomas (PPGLs) are catecholamine-secreting
neuroendocrine tumours characterised by high rates of heritability and genetic
heterogeneity. Despite advances in the genetic diagnosis and improved
understanding of the molecular aberrations underlying these tumours, predictive
markers of malignancy remain scarce, limiting the outlook of patients with
metastatic PPGL. The identification of robust predictive markers remains the most
pressing challenge in PPGL management, so that the potential of targeted therapy
to impact patient care can be fully realised.
PMID- 29333261
TI - Sleep apnea and its role in transportation safety.
AB - Obstructive sleep apnea (OSA) is a main cause of excessive daytime sleepiness and
increases the risk for driving accidents, which can be normalized by treatment
with continuous positive airway pressure ventilation. Since it is estimated that
OSA is not diagnosed in about 80% of cases, recognition of patients at risk for
driving accidents is a problem from both medical and societal points of view.
Strategies to screen and identify subjects at high risk for driving accidents are
under study in order to improve safety on the road, especially for commercial
drivers, who show a high prevalence of OSA.
PMID- 29333260
TI - Use of electroanalgesia and laser therapies as alternatives to opioids for acute
and chronic pain management.
AB - The use of opioid analgesics for postoperative pain management has contributed to
the global opioid epidemic. It was recently reported that prescription opioid
analgesic use often continued after major joint replacement surgery even though
patients were no longer experiencing joint pain. The use of epidural local
analgesia for perioperative pain management was not found to be protective
against persistent opioid use in a large cohort of opioid-naive patients
undergoing abdominal surgery. In a retrospective study involving over 390,000
outpatients more than 66 years of age who underwent minor ambulatory surgery
procedures, patients receiving a prescription opioid analgesic within 7 days of
discharge were 44% more likely to continue using opioids 1 year after surgery. In
a review of 11 million patients undergoing elective surgery from 2002 to 2011,
both opioid overdoses and opioid dependence were found to be increasing over
time. Opioid-dependent surgical patients were more likely to experience
postoperative pulmonary complications, require longer hospital stays, and
increase costs to the health-care system. The Centers for Disease Control and
Prevention emphasized the importance of finding alternatives to opioid medication
for treating pain. In the new clinical practice guidelines for back pain, the
authors endorsed the use of non-pharmacologic therapies. However, one of the more
widely used non-pharmacologic treatments for chronic pain (namely radiofrequency
ablation therapy) was recently reported to have no clinical benefit. Therefore,
this clinical commentary will review evidence in the peer-reviewed literature
supporting the use of electroanalgesia and laser therapies for treating acute
pain, cervical (neck) pain, low back pain, persistent post-surgical pain after
spine surgery ("failed back syndrome"), major joint replacements, and abdominal
surgery as well as other common chronic pain syndromes (for example, myofascial
pain, peripheral neuropathic pain, fibromyalgia, degenerative joint
disease/osteoarthritis, and migraine headaches).
PMID- 29333262
TI - Recent advances in the biology and therapy of medullary thyroid carcinoma.
AB - Medullary thyroid cancer (MTC) is a relatively uncommon yet prognostically
significant thyroid cancer. Several recent advances in the biology and current or
potential treatment of MTC are notable. These include a new understanding of the
developmental biology of the thyroid C cell, which heretofore was thought to
develop from the neural crest. RET, encoded by the most common driver gene in
MTC, has been shown to be a dual function kinase, thus expanding its potential
substrate repertoire. Promising new therapeutic developments are occurring; many
have recently progressed to clinical development. There are new insights into RET
inhibitor therapy for MTC. New strategies are being developed to inhibit the RAS
proteins, which are potential therapeutic targets in MTC. Potential emerging
immunotherapies for MTC are discussed. However, gaps in our knowledge of the
basic biology of the C cell, its transformation to MTC, and the mechanisms of
resistance to therapy impede progress; further research in these areas would have
a substantial impact on the field.
PMID- 29333264
TI - How anthropogenic shifts in plant community composition alter soil food webs.
AB - There are great concerns about the impacts of soil biodiversity loss on ecosystem
functions and services such as nutrient cycling, food production, and carbon
storage. A diverse community of soil organisms that together comprise a complex
food web mediates such ecosystem functions and services. Recent advances have
shed light on the key drivers of soil food web structure, but a conceptual
integration is lacking. Here, we explore how human-induced changes in plant
community composition influence soil food webs. We present a framework describing
the mechanistic underpinnings of how shifts in plant litter and root traits and
microclimatic variables impact on the diversity, structure, and function of the
soil food web. We then illustrate our framework by discussing how shifts in plant
communities resulting from land-use change, climatic change, and species
invasions affect soil food web structure and functioning. We argue that
unravelling the mechanistic links between plant community trait composition and
soil food webs is essential to understanding the cascading effects of
anthropogenic shifts in plant communities on ecosystem functions and services.
PMID- 29333265
TI - The Effects of a Home-based Intervention Conducted by College Students for Young
Children with Developmental Delays in Vietnam.
AB - Objectives: The project assessed the efficacy of a home-based intervention
program for young children (n= 64, ages ranging from 3-6 years) with
developmental delays in Vietnam. It was hypothesized that the children in the
intervention group would show greater progress in adaptive behavior than the
children in the control group. Methods: Assessment of the program efficacy was
carried out by comparing children who received services for 6 months and those
who did not. Children who were recognized as having developmental delays by
teachers in kindergarten programs, and confirmed by trained evaluators based on
the Vineland Adaptive Behavior Scale-II (VABS-II), were randomly assigned to
intervention and control groups. Twenty student teachers were recruited from a
teaching university and were provided with pre-program training and ongoing
supervision. Results: The outcomes of the program were examined at 0, 3, and 6
months using the VABS-II. The intervention group improved significantly more than
the control group in overall adaptive functioning and in the areas of
communication, social skills and motor skills. Conclusion: The project is one of
only a few early intervention projects to apply randomized control trials in a
low-middle-income country. The results demonstrate the feasibility of carrying
out the intervention program using teachers with no prior experience of working
with children with delays/disabilities, where professional resources are scarce
for this population.
PMID- 29333266
TI - Evaluation of a Health Education Intervention to Improve Knowledge, Skills,
Behavioral Intentions and Resources Associated with Preventable Determinants of
Infant Mortality.
AB - Mississippi has the highest rate of infant mortality in the nation (9.3 infant
deaths for 1,000 live births). A health disparity exists between white infants
(6.2) and black infants (13.0). This project reports on the effectiveness of a
pilot educational program, Healthy Moms and Healthy Babies, which sought to
improve knowledge, skills, behavioral intentions and resources related to
preventable determinants of infant mortality. A curriculum was developed and
piloted with women who were currently pregnant, thinking of becoming pregnant or
who had an infant <1 year old. Local Head Start Centers offered recruiting
assistance and meeting space for the sessions. Six content areas were developed
which addressed pre- and postnatal nutrition and physical activity, smoking,
breastfeeding, maternal mental health and safe infant sleep. Sixteen objectives
were evaluated to determine intervention effectiveness. Participants were very
satisfied with the program overall. Fourteen of sixteen objectives were met.
Unmet objectives were gaining the skill of interpreting a nutritional label
(Objective 75.0%, Observed 71.4%) and being able to name five health benefits of
breastfeeding (Objective 85.0%, Observed 81.0%). Future programs will incorporate
participant feedback which included allowing more time to learn about
interpreting food labels and addressing financial stress. Reducing preterm birth
is a national public health priority. Addressing knowledge gaps through risk
reduction education may reduce behaviors associated with determinants of infant
mortality such as low birth weight and preterm birth. Head Start Centers are
convenient locations that can serve as hubs of education for the entire family.
Addressing knowledge gaps through risk-reduction education and providing adequate
resources for smoking cessation and lactation support may increase knowledge and
skills and reduce behaviors associated with determinants of infant mortality such
as low birth weight and preterm birth.
PMID- 29333263
TI - Vancomycin-resistant enterococcus infection in the hematopoietic stem cell
transplant recipient: an overview of epidemiology, management, and prevention.
AB - Vancomycin-resistant enterococcus (VRE) is now one of the leading causes of
nosocomial infections in the United States. Hematopoietic stem cell
transplantation (HSCT) recipients are at increased risk of VRE colonization and
infection. VRE has emerged as a major cause of bacteremia in this population,
raising important clinical questions regarding the role and impact of VRE
colonization and infection in HSCT outcomes as well as the optimal means of
prevention and treatment. We review here the published literature and scientific
advances addressing these thorny issues and provide a rational framework for
their approach.
PMID- 29333267
TI - Type 1 diabetes genome-wide association studies: not to be lost in translation.
AB - Genetic studies have identified >60 loci associated with the risk of developing
type 1 diabetes (T1D). The vast majority of these are identified by genome-wide
association studies (GWAS) using large case-control cohorts of European ancestry.
More than 80% of the heritability of T1D can be explained by GWAS data in this
population group. However, with few exceptions, their individual contribution to
T1D risk is low and understanding their function in disease biology remains a
huge challenge. GWAS on its own does not inform us in detail on disease
mechanisms, but the combination of GWAS data with other omics-data is beginning
to advance our understanding of T1D etiology and pathogenesis. Current knowledge
supports the notion that genetic variation in both pancreatic beta cells and in
immune cells is central in mediating T1D risk. Advances, perspectives and
limitations of GWAS are discussed in this review.
PMID- 29333269
TI - The immune system of the liver: 50 years of strangeness.
PMID- 29333268
TI - Progress of genome-wide association studies of ankylosing spondylitis.
AB - Ankylosing spondylitis (AS) is an immune-mediated arthritis which primarily
affects the spine and sacroiliac joints. Significant progress has been made in
discovery of genetic associations with AS by genome-wide association studies
(GWAS) over past decade. These findings have uncovered novel pathways involved
pathogenesis of the disease and have led to introduction of novel therapeutic
treatments for AS. In this Review, we discuss the genetic variations associated
with AS identified by GWAS, the major pathways revealed by these AS-associated
variations and critical cell types involved in AS development.
PMID- 29333271
TI - Childhood asthma prevalence: cross-sectional record linkage study comparing
parent-reported wheeze with general practitioner-recorded asthma diagnoses from
primary care electronic health records in Wales.
AB - Introduction: Electronic health records (EHRs) are increasingly used to estimate
the prevalence of childhood asthma. The relation of these estimates to those
obtained from parent-reported wheezing suggestive of asthma is unclear. We
hypothesised that parent-reported wheezing would be more prevalent than general
practitioner (GP)-recorded asthma diagnoses in preschool-aged children. Methods:
1529 of 1840 (83%) Millennium Cohort Study children registered with GPs in the
Welsh Secure Anonymised Information Linkage databank were linked. Prevalences of
parent-reported wheezing and GP-recorded asthma diagnoses in the previous 12
months were estimated, respectively, from parent report at ages 3, 5, 7 and 11
years, and from Read codes for asthma diagnoses and prescriptions based on GP
EHRs over the same time period. Prevalences were weighted to account for
clustered survey design and non-response. Cohen's kappa statistics were used to
assess agreement. Results: Parent-reported wheezing was more prevalent than GP
recorded asthma diagnoses at 3 and 5 years. Both diminished with age: by age 11,
prevalences of parent-reported wheezing and GP-recorded asthma diagnosis were
12.9% (95% CI 10.6 to 15.4) and 10.9% (8.8 to 13.3), respectively (difference: 2%
(-0.5 to 4.5)). Other GP-recorded respiratory diagnoses accounted for 45.7% (95%
CI 37.7 to 53.9) and 44.8% (33.9 to 56.2) of the excess in parent-reported
wheezing at ages 3 and 5 years, respectively. Conclusion: Parent-reported
wheezing is more prevalent than GP-recorded asthma diagnoses in the preschool
years, and this difference diminishes in primary school-aged children. Further
research is needed to evaluate the implications of these differences for the
characterisation of longitudinal childhood asthma phenotypes from EHRs.
PMID- 29333270
TI - Lessons from ten years of genome-wide association studies of asthma.
AB - Twenty-five genome-wide association studies (GWAS) of asthma were published
between 2007 and 2016, the largest with a sample size of 157242 individuals.
Across these studies, 39 genetic variants in low linkage disequilibrium (LD) with
each other were reported to associate with disease risk at a significance
threshold of P<5 * 10-8, including 31 in populations of European ancestry.
Results from analyses of the UK Biobank data (n=380 503) indicate that at least
28 of the 31 associations reported in Europeans represent true-positive findings,
collectively explaining 2.5% of the variation in disease liability (median of
0.06% per variant). We identified 49 transcripts as likely target genes of the
published asthma risk variants, mostly based on LD with expression quantitative
trait loci (eQTL). Of these genes, 16 were previously implicated in disease
pathophysiology by functional studies, including TSLP, TNFSF4, ADORA1, CHIT1 and
USF1. In contrast, at present, there is limited or no functional evidence
directly implicating the remaining 33 likely target genes in asthma
pathophysiology. Some of these genes have a known function that is relevant to
allergic disease, including F11R, CD247, PGAP3, AAGAB, CAMK4 and PEX14, and so
could be prioritized for functional follow-up. We conclude by highlighting three
areas of research that are essential to help translate GWAS findings into
clinical research or practice, namely validation of target gene predictions,
understanding target gene function and their role in disease pathophysiology and
genomics-guided prioritization of targets for drug development.
PMID- 29333272
TI - Peracetic acid disinfection kinetics for combined sewer overflows: indicator
organisms, antibiotic resistance genes, and microbial community.
AB - Combined sewer overflows (CSOs) degrade water quality and end-of-pipe treatment
is one potential solution for retrofitting this outdated infrastructure. The goal
of this research was to evaluate peracetic acid (PAA) as a disinfectant for CSOs
using viability based molecular methods for antibiotic resistance genes (ARGs),
indicator organism marker gene BacHum, and 16S rRNA genes. Simulated CSO effluent
was prepared using 23-40% wastewater, representing the higher end of the range of
wastewater concentrations reported in CSO effluent. PAA residual following
disinfection was greatest for samples with the lowest initial COD. Treatment of
simulated CSO effluent (23% wastewater) with 100 mg?min/L PAA (5 mg/L PAA, 20
min) was needed to reduce viable cell sul1, tet(G), and BacHum (1.0+/-0.63-3.2+/
0.25-log) while 25 to 50 mg*min/L PAA (5 mg/L PAA, 5-10 min) was needed to reduce
viable cell loads (0.62+/-0.56-1.6+/-0.08-log) in 40% wastewater from a different
municipal treatment plant. Increasing contact time after the initial decrease in
viable cell gene copies did not significantly improve treatment. A much greater
applied Ct of 1200 mg?min/L PAA (20 mg/L PAA, 60 min) was required for
significant log reduction of 16S rRNA genes (3.29+/-0.13-log). No significant
losses of mexB were observed during the study. Data were fitted to a Chick-Watson
model and resulting inactivation constants for sul1 and tet(G) > BacHum > 16S
rRNA. Amplicon sequencing of the 16S rRNA gene indicated the initial viable and
total microbial communities were distinct and that treatment with PAA resulted in
marked increases of the relative abundance of select phyla, particularly
Clostridia which increased by 1-1.5 orders of magnitude. Results confirm that
membrane disruption is a mechanism for PAA disinfection and further treatment is
needed to reduce total ARGs in CSO effluent.
PMID- 29333273
TI - Changes in androstenedione, dehydroepiandrosterone, testosterone, estradiol, and
estrone over the menopausal transition.
AB - Background: Previous reports have noted that dehydroepiandrosterone-sulfate
(DHEAS) increases prior to the final menstrual period (FMP) and remains stable
beyond the FMP. How DHEAS concentrations correspond with other sex hormones
across the menopausal transition (MT) including androstenedione (A4),
testosterone (T), estrone (E1), and estradiol (E2) is not known. Our objective
was to examine how DHEAS, A4, T, E1, and E2 changed across the MT by White vs.
African-American (AA) race/ethnicity. Methods: We conducted a longitudinal
observational analysis of a subgroup of women from the Study of Women's Health
Across the Nation observed over 4 visits prior to and 4 visits after the FMP (n =
110 women over 9 years for 990 observations). The main outcome measures were
DHEAS, A4, T, E1, and E2. Results: Compared to the decline in E2 concentrations,
androgen concentrations declined minimally over the MT. T (beta 9.180, p <
0.0001) and E1 (beta 11.365, p < 0.0001) were higher in Whites than in AAs, while
elevations in DHEAS (beta 28.80, p = 0.061) and A4 (beta 0.2556, p = 0.052) were
borderline. Log-transformed E2 was similar between Whites and AAs (beta 0.0764, p
= 0.272). Body mass index (BMI) was not significantly associated with
concentrations of androgens or E1 over time. Conclusion: This report suggests
that the declines in E2 during the 4 years before and after the FMP are
accompanied by minimal changes in DHEAS, A4, T, and E1. There are modest
differences between Whites and AAs and minimal differences by BMI.
PMID- 29333274
TI - Report of an Italian family carrying a typical Indian variant of the Nilgiris
tribal groups resulting from a de novo occurrence.
AB - G6PD deficiency is quite common in Italy where it is characterized by extreme
molecular and biochemical heterogeneity. We report a 15-year-old Italian boy with
G6PD Nilgiri (c.593G>A, p.Arg198His), a typical Indian variant of the Nilgiris
tribal groups. Further, this variant was biochemically characterized, and the
molecular screening of the family highlighted a de novo mutational event. To
date, this family is the first Caucasian family carrying the G6PD Nilgiri
variant.
PMID- 29333275
TI - Barriers to care for chronic hepatitis C in the direct-acting antiviral era: a
single-centre experience.
AB - Background: Cure rates for chronic hepatitis C have improved dramatically with
direct-acting antivirals (DAAs), but treatment barriers remain. We aimed to
compare treatment initiation rates and barriers across both interferon-based and
DAA-based eras. Methods: We conducted a retrospective cohort study of all
patients with chronic hepatitis C seen at an academic hepatology clinic from 1999
to 2016. Patients were identified to have chronic hepatitis C by the
International Classification of Diseases, Ninth Revision codes, and the diagnosis
was validated by chart review. Patients were excluded if they did not have at
least one visit in hepatology clinic, were under 18 years old or had prior
treatment with DAA therapy. Patients were placed in the DAA group if they were
seen after 1 January 2014 and had not yet achieved virological cure with prior
treatment. All others were considered in the interferon group. Results: 3202
patients were included (interferon era: n=2688; DAA era: n=514). Despite higher
rates of decompensated cirrhosis and medical comorbidities in the DAA era,
treatment and sustained virological response rates increased significantly when
compared with the interferon era (76.7% vs 22.3%, P<0.001; 88.8% vs 55%, P<0.001,
respectively). Lack of follow-up remained a significant reason for non-treatment
in both groups (DAA era=24% and interferon era=45%). An additional 8% of patients
in the DAA era were not treated due to insurance or issues with cost. In the DAA
era, African-Americans, compared with Caucasians, had significantly lower odds of
being treated (OR=0.37, P=0.02). Conclusions: Despite higher rates of medical
comorbidities in the DAA era, considerable treatment challenges remain including
cost, loss to follow-up and ethnic disparities.
PMID- 29333276
TI - Neuropsychiatric performance and treatment of hepatitis C with direct-acting
antivirals: a prospective study.
AB - Background: Since direct-acting antivirals (DAAs) have been approved for the
treatment of hepatitis C virus (HCV) infection, a small series of patients with
new-onset neuropsychiatric alterations have been referred to us. We therefore set
out to study neuropsychiatric function in relation to DAAs prospectively.
Methods: Ten patients with cirrhosis and 12 post-liver transplant (post-LT)
patients were enrolled. All underwent wake electroencephalography (EEG) and a
neuropsychological evaluation (paper and pencil battery, simple/choice reaction
times, working memory task) at baseline, at the end of treatment with DAAs and
after 6 months. At the same time points, full blood count, liver/kidney function
tests, quantitative HCV RNA, ammonia and immunosuppressant drug levels were
obtained, as appropriate. Results: Patients with cirrhosis were significantly
older than post-LT patients (65+/-12 vs 55+/-7 years; P<0.05). Neuropsychological
performance and wake EEG were comparable in the two groups at baseline. At the
end of a course of treatment with DAAs, a significant slowing in choice reaction
times and in the EEG (increased relative delta power) was observed in patients
with cirrhosis, which resolved after 6 months. In contrast, no significant
changes over time were observed in the neuropsychiatric performance of post-LT
patients. No significant associations were observed between neuropsychiatric
performance and stand-alone/combined laboratory variables. Conclusion: Some
degree of neuropsychiatric impairment was observed in relation to treatment with
DAAs in patients with cirrhosis, but not in post-LT patients, suggesting that the
former may be sensitive to mild DAA neurotoxicity.
PMID- 29333277
TI - Familial risks for gallstones in the population of Sweden.
AB - Objectives: Gallstone disease (cholelithiasis) has a familial component, but
detailed data on the modification of familial risk are lacking. Using nationwide
hospital and population records, we aimed to determine detailed familial risks
for medically diagnosed gallstone disease. Design: Subjects were obtained from
the Multigeneration Register, which contains family data on the Swedish
population, and patients with gallstone disease were identified from the Hospital
Discharge Register (1964-2015) and the Outpatient Register (2001-2015).
Standardised incidence ratios (SIRs) were calculated as the ratio of observed to
expected number of cases. Results: Gallstone disease was diagnosed in 660 732
patients, with an overall incidence of 131 per 100 000 person-years. Familial
cases accounted for 36.0% of all patients with gallstone disease. Of these, 50.9%
had a parental family history (SIR 1.62), 35.1% had a sibling history (SIR 1.75)
and 14.0% had a parental+sibling history (SIR 2.58). Among a total of 54 630
affected siblings, 84.4% were sibling pairs (SIR 1.55). However, the remaining
15.6% of the affected siblings constituted the high-risk group of multiple
affected siblings and an SIR >10; these persons accounted for 7.7% of all
familial cases. The spousal risk was only slightly increased to 1.18.
Conclusions: Overall, the results point to the underlying genetic causes for the
observed familial clustering, which may involve polygenic gene-environmental
interactions for most familial cases but high-risk genes in close to 10% of
cases. Family histories should be taken into account in the medical setting and
used for counselling of at-risk individuals.
PMID- 29333278
TI - Clinical influence of exercise therapy on sarcopenia in patients with chronic
pancreatitis: a study protocol for a randomised controlled trial.
AB - Introduction and purpose: Chronic pancreatitis (CP) involves progressive
inflammatory changes to the pancreas and can lead to permanent structural damage
and impairment of both endocrine and exocrine functions. Current reports
highlight a rise in the incidence and prevalence of CP. However, there is limited
data currently available concerning patients with CP undergoing exercise therapy
(ET). We aim to prospectively examine the influence of ET on sarcopenia in
patients with CP. Methods and analysis: A detailed evaluation of the nutritional
condition and the daily physical activities of each participant will be conducted
prior to entering the study. Our patients will be randomly allocated to either:
(1) the ET group or (2) the control group. In the ET group, our patients with CP
will receive nutritional guidance once a month. The patients with CP will also be
instructed to perform exercises with >3 metabolic equivalents (mets; energy
consumption in physical activities/resting metabolic rate) for 60 min/day and to
perform exercises >23 mets/week. The primary end point will be an improvement in
sarcopenia, defined as an increase in muscle mass and muscle strength, at 3
months postrandomisation. A comparison of the amelioration of sarcopenia in the
two groups will be undertaken. Ethics and dissemination: The Institutional Review
Board at Hyogo College of Medicine approved this study protocol (approval no.
2766). Final data will be publicly announced. A report releasing the study
results will be submitted for publication to an appropriate journal. Trial
registration number: UMIN000029263; Pre-results. No patient is registered at the
submission of our manuscript.
PMID- 29333280
TI - Correction: ProNGF-p75NTR axis plays a proinflammatory role in inflamed joints: a
novel pathogenic mechanism in chronic arthritis.
AB - [This corrects the article DOI: 10.1136/rmdopen-2017-000441.][This corrects the
article DOI: 10.1136/rmdopen-2017-000441.].
PMID- 29333279
TI - Increased supraspinatus tendon thickness following fatigue loading in rotator
cuff tendinopathy: potential implications for exercise therapy.
AB - Background/aim: Exercise imparts a load on tendon tissue that leads to changes in
tendon properties. Studies suggest that loading immediately reduces tendon
thickness, with a loss of this response in symptomatic tendinopathy. No studies
investigating the response of tendon dimensions to load for the rotator cuff
tendons exist. This study aimed to examine the short-term effect of loading on
the thickness of the supraspinatus tendon and acromiohumeral distance those with
and without rotator cuff tendinopathy. Methods: Participants were 20 painfree
controls, and 23 people with painful rotator cuff tendinopathy. Supraspinatus
tendon thickness and acromiohumeral distance were measured using ultrasound scans
before, and at three time points after loading (1, 6 and 24 hours). Loading
involved isokinetic eccentric and concentric external rotation and abduction.
Results: There was a significant increase in supraspinatus tendon thickness in
the pain group at 1 (7%, ?=0.38, 95% CI 0.19 to 0.57) and 6 hours (11%, ?=0.53,
95% CI 0.34 to 0.71), although only the 6 hours difference exceeded minimal
detectable difference. In contrast, there was a small non-significant reduction
in thickness in controls. The acromiohumeral distance reduced significantly in
both groups at 1 hour (controls: ?=0.64, 95% CI 0.38 to 0.90; pain: ?=1.1, 95% CI
0.85 to 1.33), with a larger change from baseline in the pain group. Conclusion:
Those diagnosed with painful supraspinatus tendinopathy demonstrated increased
thickening with delayed return to baseline following loading. Rehabilitation
professionals may need to take into account the impact of loading to fatigue when
planning rehabilitation programmes.
PMID- 29333281
TI - Controversies and consensus of neoadjuvant chemotherapy in soft-tissue sarcomas.
AB - Together with surgery and radiotherapy, systemic treatment with cytotoxic
chemotherapy and molecular targeted agents is one of the main therapeutic pillars
in the treatment of soft-tissue sarcomas and is the mainstay of treatment in
patients with advanced or metastatic disease. Unlike other more common
malignancies such as breast and colorectal cancer, the role of chemotherapy when
used in the adjuvant setting in soft-tissue sarcomas is less well defined.
Results from prior studies have been conflicting, in part due to the
heterogeneity and rarity of the disease, and large-scale meta-analysis has been
performed to address this issue. Neoadjuvant chemotherapy, defined as the use of
chemotherapy before definitive treatment with surgery or radiotherapy, has
distinct theoretical and practical advantages, which can potentially be
beneficial to the patient. However, the currently available evidence to support
its use is even more scarce. In this review article, we describe the current
established data behind the use of adjuvant chemotherapy in selected patients
with localised soft-tissue sarcomas and, through extrapolation of available data,
discuss the potential role of it when used in the upfront setting.
PMID- 29333283
TI - Adverse effects of exposure to armed conflict on pregnancy: a systematic review.
AB - Introduction: Exposure to armed conflict has manifold implications for both
military and civilian populations. Prenatal stress has detrimental effects on
both obstetric outcomes, fetal development and the development of an individual
later in life. As well as causing stress to the mother, armed conflicts can
decimate local infrastructures making it increasingly difficult to access
antenatal and general healthcare. The present review is particularly salient in
light of the many ongoing current conflicts. It examines the impacts of exposure
to armed conflicts on the pregnancy outcomes. Methods: A thorough literature
search was carried out on three databases using MeSH and truncation terms. 13
studies were included in the final analysis relating to mothers exposed to armed
conflicts since 1990. Results: The studies include data from 1 172 151 patients:
mothers from Libya, Bosnia, Herzegovina, Israel, Palestine, Kosovo, Yugoslavia,
Nepal, Somalia, Iraq, Kuwait and Afghanistan. There is evidence of an increased
risk of mothers giving birth to babies of low birth weight as reported in nine
included studies. All have a degree of bias, with four at lower and five at
higher risk of bias, either not adjusting for confounders or not employing robust
measures of exposure to conflict. Further evidence suggested an increase in the
incidence of miscarriage, stillbirth, prematurity, congenital abnormalities,
miscarriage and premature rupture of membranes among mothers exposed to armed
conflict. Conclusion: Despite the varying degrees of bias which must be
considered for the available evidence, the data with the lowest risk of bias
suggest a relationship between exposure to armed conflict and low birth weight.
In light of the current level of displacement experienced by such populations,
the identification of pregnancies at risk could improve the efficacy of antenatal
care. Clinicians should consider additional ultrasound scanning where appropriate
to monitor for restricted growth in such pregnancies.
PMID- 29333282
TI - Relationship between growth and illness, enteropathogens and dietary intakes in
the first 2 years of life: findings from the MAL-ED birth cohort study.
AB - Background: Dietary and illness factors affect risk of growth faltering; the role
of enteropathogens is less clear. As part of the Etiology, Risk Factors and
Interactions of Enteric Infections and Malnutrition and the Consequences for
Child Health and Development (MAL-ED) study, we quantify the effects of
enteropathogen infection, diarrhoea and diet on child growth. Methods: Newborns
were enrolled and followed until 24 months. Length and weight were assessed
monthly. Illnesses and breastfeeding practices were documented biweekly; from 9
to 24 months, non-breast milk intakes were quantified monthly. Routinely
collected non-diarrhoeal stools were analysed for a broad array of
enteropathogens. A linear piecewise spline model was used to quantify
associations of each factor with growth velocity in seven of eight MAL-ED sites;
cumulative effects on attained size at 24 months were estimated for mean, low
(10th percentile) and high (90th percentile) exposure levels. Additionally, the
six most prevalent enteropathogens were evaluated for their effects on growth.
Results: Diarrhoea did not have a statistically significant effect on growth.
Children with high enteropathogen exposure were estimated to be 1.21+/-0.33 cm
(p<0.001; 0.39 length for age (LAZ)) shorter and 0.08+/-0.15 kg (p=0.60; 0.08
weight-for-age (WAZ)) lighter at 24 months, on average, than children with low
exposure. Campylobacter and enteroaggregativeEscherichia coli detections were
associated with deficits of 0.83+/-0.33 and 0.85+/-0.31 cm in length (p=0.011 and
0.001) and 0.22+/-0.15 and 0.09+/-0.14 kg in weight (p=0.14 and 0.52),
respectively. Children with low energy intakes and protein density were estimated
to be 1.39+/-0.33 cm (p<0.001; 0.42 LAZ) shorter and 0.81+/-0.15 kg (p<0.001;
0.65 WAZ) lighter at 24 months than those with high intakes. Conclusions:
Reducing enteropathogen burden and improving energy and protein density of
complementary foods could reduce stunting.
PMID- 29333285
TI - Wealth inequality as a predictor of HIV-related knowledge in Nigeria.
AB - Introduction: Considering the high state-level heterogeneity of HIV prevalence
and socioeconomic characteristics in Nigeria, it is a relevant setting for
studies into the socioeconomic correlates of HIV-related knowledge. Although the
relationship between absolute poverty and HIV transmission has been studied, the
role of wealth inequality in the dynamics of the HIV epidemic has yet to be
investigated in Nigeria. The current study, therefore, investigates wealth
inequality and other sociodemographic covariates as predictors of HIV-related
knowledge, in order to identify subgroups of the Nigerian population that would
benefit from HIV preventive interventions. Methods: This study used the
nationally representative 2013 Nigerian Demographic and Health Survey (NDHS). HIV
related knowledge was computed as a total score based on HIV-related knowledge
indicators in the NDHS, dichotomised using the sample median as the cut-off.
Wealth inequality and other relevant sociodemographic variables were introduced
into a logistic regression model based on their significance in bivariate
analyses. ORs derived from the model were interpreted to identify risk groups for
low HIV-related knowledge after adjusting for confounding factors. Results: The
regression model indicated that individuals with lower literacy levels were
almost twice as likely as literate respondents to have low HIV-related knowledge
(adjusted OR (AOR): 1.95, 95% CI 1.85 to 2.05, P<0.001), and individuals in the
upper wealth quintile were less than half as likely than those in the lower
wealth quintile to have low HIV-related knowledge (AOR: 0.40, 95% CI 0.35 to
0.46, P<0.001). Women were also more than twice as likely as men to have low HIV
related knowledge at each level of wealth inequality. In addition, women were 80%
less likely to have low mother-to-child transmission knowledge than men, but had
over 1.5 times higher odds of having poor knowledge of HIV risk reduction
measures. Ethnicity, religious affiliation, relationship status and residing in
rural areas were additional significant predictors of HIV-related knowledge.
Conclusion: HIV-related knowledge in this sample is generally low among women,
those with low literacy levels, the poor, the unemployed, those residing in rural
areas, those with traditional religious beliefs and those living in states with
the highest wealth inequality ratios. The identification of these risk groups for
low HIV-related knowledge facilitates the implementation of future evidence-based
interventions among these groups in order to potentially reduce HIV transmission.
PMID- 29333284
TI - Does greater individual social capital improve the management of hypertension?
Cross-national analysis of 61 229 individuals in 21 countries.
AB - Introduction: Social capital, characterised by trust, reciprocity and
cooperation, is positively associated with a number of health outcomes. We test
the hypothesis that among hypertensive individuals, those with greater social
capital are more likely to have their hypertension detected, treated and
controlled. Methods: Cross-sectional data from 21 countries in the Prospective
Urban and Rural Epidemiology study were collected covering 61 229 hypertensive
individuals aged 35-70 years, their households and the 656 communities in which
they live. Outcomes include whether hypertensive participants have their
condition detected, treated and/or controlled. Multivariate statistical models
adjusting for community fixed effects were used to assess the associations of
three social capital measures: (1) membership of any social organisation, (2)
trust in other people and (3) trust in organisations, stratified into high-income
and low-income country samples. Results: In low-income countries, membership of
any social organisation was associated with a 3% greater likelihood of having
one's hypertension detected and controlled, while greater trust in organisations
significantly increased the likelihood of detection by 4%. These associations
were not observed among participants in high-income countries. Conclusion:
Although the observed associations are modest, some aspects of social capital are
associated with better management of hypertension in low-income countries where
health systems are often weak. Given that hypertension affects millions in these
countries, even modest gains at all points along the treatment pathway could
improve management for many, and translate into the prevention of thousands of
cardiovascular events each year.
PMID- 29333286
TI - Prevalence and determinants of tobacco use among young people in The Gambia.
AB - Introduction: Tobacco consumption and consequent morbidity and mortality are
expected to grow most markedly over coming decades in low-income and middle
income countries (LMICs). Preventing tobacco experimentation and uptake among
young people in LMICs is therefore vital. However, data on smoking in these
countries, particularly in sub-Saharan Africa, remain sparse. Method: We used two
stage cluster random sampling to select students in upper and senior secondary
schools throughout The Gambia, and a self-administered questionnaire to collect
data on their tobacco use, risk factors and demographic details. Results: Of 10
392 eligible students, 10 289 (99%; 55% girls and 44% boys, age 12-20 years)
participated. The prevalence of ever smoking cigarettes, cigars or pipes was
16.7% (25.7% boys and 9.4% girls) and current (past 30 days) smoking 4.5% (7.9%
boys and 1.5% girls). Smoking was more common among students attending private
schools (OR 1.69, 95% CI 1.29 to 2.22), of Christian or other faiths compared
with Muslims, living with parents (OR 1.39, 95% CI 1.06 to 1.81), who had smoking
allowed in their homes (OR 1.67, 95% CI 1.30 to 2.13), with family members who
smoked or had one or more friends who smoked. Most (55.6%) smokers want to stop,
but only 22% received any stop smoking support. Ever smoking of shisha, at 8.1%,
was unexpectedly high, and relatively prevalent among girls (11.4% of boys and
5.4% of girls). Conclusions: Tobacco use is common among young people in The
Gambia. Shisha smoking is also common in this population, and in relative terms
especially among girls. Further work is required to determine whether this is a
problem local to The Gambia or reflects a wider pattern of tobacco use in sub
Saharan Africa.
PMID- 29333287
TI - Vertical and horizontal equity of funding for malaria control: a global
multisource funding analysis for 2006-2010.
AB - Background: International and domestic funding for malaria is critically
important to achieve the Sustainable Development Goals. Its equitable
distribution is key in ensuring that the available, scarce, resources are
deployed efficiently for improved progress and a sustained response that enables
eradication. Methods: We used concentration curves and concentration indices to
assess inequalities in malaria funding by different donors across countries,
measuring both horizontal and vertical equity. Horizontal equity assesses whether
funding is distributed in proportion to health needs, whereas vertical equity
examines whether unequal economic needs are addressed by appropriately unequal
funding. We computed the Health Inequity Index and the Kakwani Index to assess
the former and the latter, respectively. We used data from the World Bank, Global
Fund, Unicef, President's Malaria Initiative and the Malaria Atlas Project to
assess the distribution of funding against need for 94 countries. National gross
domestic product per capita was used as a proxy for economic need and 'population
at-risk' for health need. Findings: The level and direction of inequity varies
across funding sources. Unicef and the President's Malaria Initiative were the
most horizontally inequitable (pro-poor). Inequity as shown by the Health
Inequity Index for Unicef decreased from -0.40 (P<0.05) in 2006 to -0.25 (P<0.10)
in 2008, and increased again to -0.58 (P<0.01) in 2009. For President's Malaria
Initiative, it increased from -0.19 (P>0.10) in 2006 to -0.38 (P<0.05) in 2008,
and decreased to -0.36 (P<0.10) in 2010. Domestic funding was inequitable (pro
rich) with inequity increasing from 0.28 (P<0.01) in 2006 to 0.39 (P<0.01) in
2009, and then decreasing to 0.22 (P<0.10) in 2010. Funding from the World Bank
and the Global Fund was distributed proportionally according to need. In terms of
vertical inequity, all sources were progressive: Unicef and the President's
Malaria Initiative were the most progressive with the Kakwani Indices ranging
from -0.97 (P<0.01) to -1.29 (P<0.01), and -0.90 (P<0.01) to -1.10 (P<0.01),
respectively. Conclusion: Our results suggest that external funding of malaria
treatment tends to be allocated to countries with higher health and economic need
but not in proportion to their relative health need and income when compared to
other countries. While malaria eradication might require funders to
disproportionally allocate funding that goes beyond (financial and health) need,
our analysis highlights that funders might potentially be targeting in excess
certain countries. Regular assessments of need and greater coordination among
donors are necessary for equitable resource allocation, to improve and sustain
progress with malaria control and elimination.
PMID- 29333289
TI - Localized Single-Cell Lysis and Manipulation Using Optothermally-Induced Bubbles.
AB - Localized single cells can be lysed precisely and selectively using microbubbles
optothermally generated by microsecond laser pulses. The shear stress from the
microstreaming surrounding laser-induced microbubbles and direct contact with the
surface of expanding bubbles cause the rupture of targeted cell membranes. High
resolution single-cell lysis is demonstrated: cells adjacent to targeted cells
are not lysed. It is also shown that only a portion of the cell membrane can be
punctured using this method. Both suspension and adherent cell types can be lysed
in this system, and cell manipulation can be integrated for cell-cell interaction
studies.
PMID- 29333288
TI - Variations in disability and quality of life with age and sex between eight lower
income and middle-income countries: data from the INDEPTH WHO-SAGE collaboration.
AB - Background: Disability and quality of life are key outcomes for older people.
Little is known about how these measures vary with age and gender across lower
income and middle-income countries; such information is necessary to tailor
health and social care policy to promote healthy ageing and minimise disability.
Methods: We analysed data from participants aged 50 years and over from health
and demographic surveillance system sites of the International Network for the
Demographic Evaluation of Populations and their Health Network in Ghana, Kenya,
Tanzania, South Africa, Vietnam, India, Indonesia and Bangladesh, using an
abbreviated version of the WHO Study on global AGEing survey instrument. We used
the eight-item WHO Quality of Life (WHOQoL) tool to measure quality of life and
theWHO Disability Assessment Schedule, version 2 (WHODAS-II) tool to measure
disability. We collected selected health status measures via the survey
instrument and collected demographic and socioeconomic data from linked
surveillance site information. We performed regression analyses to quantify
differences between countries in the relationship between age, gender and both
quality of life and disability, and we used anchoring vignettes to account for
differences in interpretation of disability severity. Results: We included 43 935
individuals in the analysis. Mean age was 63.7 years (SD 9.7) and 24 434 (55.6%)
were women. In unadjusted analyses across all countries, WHOQoL scores worsened
by 0.13 points (95% CI 0.12 to 0.14) per year increase in age and WHODAS scores
worsened by 0.60 points (95% CI 0.57 to 0.64). WHODAS-II and WHOQoL scores varied
markedly between countries, as did the gradient of scores with increasing age. In
regression analyses, differences were not fully explained by age, socioeconomic
status, marital status, education or health factors. Differences in disability
scores between countries were not explained by differences in anchoring vignette
responses. Conclusions: The relationship between age, sex and both disability and
quality of life varies between countries. The findings may guide tailoring of
interventions to individual country needs, although these associations require
further study.
PMID- 29333290
TI - Clinical Characteristics and Surgical Procedures for Children with Congenital
Membranous Cataract.
AB - Objective: In a group case series, the clinical characteristics of congenital
membranous cataract in children were studied to establish a system of
classification and determine the surgical method suited for each type. Methods:
Children (18 eyes) with congenital membranous cataract were examined by slit
lamp, ultrasound biomicroscopy, and operating microscopy to classify cataracts.
The clinical characteristics of congenital membranous cataract and its feature
related to the surgical method were analyzed. Results: Five major types of
congenital membranous cataracts were classified. All of the surgeries were
successful. Anterior and posterior capsulorhexis was performed using Kloti RF
capsulotomy tips. The capsular flap was removed, and anterior vitrectomy was
performed using a vitrectomy cutter. Postoperative complications included
posterior capsule opacification in 16.7% of the patients. Conclusion: Ultrasound
biomicroscopy was used successfully to classify congenital membranous cataracts
prior to surgery. Anterior and posterior capsulorhexis was performed using Kloti
RF capsulotomy tips, and capsulectomy was performed using a vitrectomy cutter.
These were effective techniques and should be considered for congenital
membranous cataract removal surgery. This trial is registered with registration
number chiCTR-OOC-17010913.
PMID- 29333291
TI - The Effect of Perioperative Topical Ketorolac 0.5% on Macular Thickness after
Uneventful Phacoemulsification.
AB - Background: To evaluate the effects of topical 0.5% ketorolac treatment combined
with topical steroids on macular thickness in cases who had uneventful
phacoemulsification surgery. Methods: 58 eyes of 58 consecutive cases were
included. The mean foveal thickness (MFT), parafoveal thickness (ParaFT), and
perifoveal thickness (PeriFT) measurements were performed with optical coherence
tomography (RTVue-100, Optovue, Fremont, CA, USA) preoperatively and at
postoperative 1 week, 1 month, and 2 months. All cases received topical 0.1%
dexamethasone postoperatively. Randomly selected cases additionally received
topical 0.5% ketorolac, which started 2 days prior to surgery. Cases who received
both topical steroids and ketorolac formed group 1 and subjects who received only
topical steroids formed group 2. Results: The increase in mean MFT at the 1st
week, 1st month, and 2nd months after surgery in group 1 was significantly lower
than group 2 (P = 0.008, P <= 0.001, and P <= 0.001, resp.). In group 1, the
increase in mean ParaFT and PeriFT was significantly lower than group 2 at the
1st and 2nd months of the surgery (P < 0.05 for all variables). Conclusions:
Topical ketorolac combined with steroids is highly efficacious in order to
prevent increment in thickness on each part of the macula even after an
uneventful phacoemulsification surgery comparing to steroid monotheraphy.
PMID- 29333292
TI - Applying Sutureless Encircling Number 41 Band and Transscleral Chandelier
Assisted Laser Retinopexy for Scleral Buckling Procedure.
AB - Purpose: To assess the outcome of sutureless encirlcing number 41 band and
transscleral laser retinopexy in uncomplicated rhegmatogenous retinal detachment
(RRD), using a wide-angle viewing system (WAVS) and chandelier endoillumination.
Methods: Prospective intervention study included 30 eyes of 30 patients
presenting with RRD of recent onset indicated for SB. All cases were treated by
sutureless encircling number 41 band and transscleral laser retinopexy.
Visualization was provided by the Resight WAVS and a single 27-gauge chandelier
endoillumination. Anatomical and visual outcomes were evaluated. Results: The
mean age of our group was 49.8 +/- 12.3 years, and the mean duration of RD was 7
(0-50) days. Twenty-four eyes (80.0%) were phakic while the remaining 6 eyes
(20%) were either pseudophakic or aphakic. The primary retinal reattachment rate
was 83.3% (25 out of 30 eyes). LogMAR visual acuity improved from 1.3 (0.30-2.0)
preoperatively to 1.0 (0.40-1.60) at first month (p = 0.002) and to 0.70 (0.20
1.92) at third month (p < 0.001). Conclusion: Sutureless encircling number 41
band with chandelier-assisted transscleral laser retinopexy is a safe and
effective technique for managing uncomplicated RRD. It provides a high primary
success rate while eliminating the complications of cryotherapy, sutures, and
broad buckles.
PMID- 29333293
TI - Corrigendum to "Genotype-Phenotype Characterization of Novel Variants in Six
Italian Patients with Familial Exudative Vitreoretinopathy".
AB - [This corrects the article DOI: 10.1155/2017/3080245.].
PMID- 29333294
TI - Addressing Adolescent Depression in Tanzania: Positive Primary Care Workforce
Outcomes Using a Training Cascade Model.
AB - Background: This is a report on the outcomes of a training program for community
clinic healthcare providers in identification, diagnosis, and treatment of
adolescent Depression in Tanzania using a training cascade model. Methods: Lead
trainers adapted a Canadian certified adolescent Depression program for use in
Tanzania to train clinic healthcare providers in the identification, diagnosis,
and treatment of Depression in young people. As part of this training program,
the knowledge, attitudes, and a number of other outcomes pertaining to healthcare
providers and healthcare practice were assessed. Results: The program
significantly, substantially, and sustainably improved provider knowledge and
confidence. Further, healthcare providers' personal help-seeking efficacy also
significantly increased as well as the clinicians' reported number of adolescent
patients identified, diagnosed, and treated for Depression. Conclusion: To our
knowledge, this is the first study reporting positive outcomes of a training
program addressing adolescent Depression in Tanzanian community clinics. These
results suggest that the application of this training cascade approach may be a
feasible model for developing the capacity of healthcare providers to address
youth Depression in a low-income, low-resource setting.
PMID- 29333295
TI - Serial Galactose-Deficient IgA1 Levels in Children with IgA Nephropathy and
Healthy Controls.
AB - Galactose-deficient IgA1 (Gd-IgA1) is a key pathogenic factor for IgA nephropathy
(IgAN) and a potential biomarker for the disease. This study examined serial
serum Gd-IgA1 levels over 1 year in 13 children with IgAN and 40 healthy
children, to determine whether or not serum Gd-IgA1 levels changed over time.
Subjects were younger than 18 years of age. Follow-up measurements were scheduled
6 and/or 12 months later. Analysis of variance and regression models for repeated
measures were used to estimate group and time effects. Serum Gd-IgA1 level was
higher in initial samples for IgAN patients compared to those of healthy children
(P < 0.0001). Serum Gd-IgA1 levels did not change over time for healthy controls
but increased for IgAN patients (P = 0.001). Serum Gd-IgA1 level was elevated for
9 children with IgAN at study entry and remained elevated. Two of the 4 IgAN
patients with initially normal Gd-IgA1 levels had a subsequent elevated level.
The persistent elevation of the serum Gd-IgA1 level in children with IgAN
enhances its utility as a potential diagnostic test for IgAN.
PMID- 29333296
TI - Determinants of Malaria Prevention and Treatment Seeking Behaviours of Pregnant
Undergraduates Resident in University Hostels, South-East Nigeria.
AB - This cross-sectional descriptive survey investigated determinants of malaria
prevention and treatment seeking behaviours of pregnant undergraduates resident
in university hostels, South-East Nigeria. Purposive sampling was used to enrol
121 accessible and consenting undergraduates with self-revealed and noticeable
pregnancy residing in twenty-three female hostels of four university campuses in
Enugu State, Nigeria. Structured interview guide developed based on reviewed
literature and WHO-recommended malaria prevention and treatment measures was used
to collect students' self-report data on malaria preventive health behaviours,
sick role behaviours, and clinic use using mixed methods. The WHO-recommended
malaria prevention measures were sparingly used. Some believed that pregnancy
does not play any role in a woman's reaction to malaria infection. Only 41
(50.6%) visited a hospital for screening and treatment. Thirty-four (28.1%) used
antimalaria medicine bought from chemist shop or over-the-counter medicines,
while 33 (27.3%) used untreated net. The students were more likely to complete
their antimalaria medicine when they were sick with malaria infection than for
prevention (p = 0.0186). Knowledge, academic schedule, cultural influence on
perception and decision-making, and accessibility of health facility were key
determinants of the women's preventive and treatment seeking behaviours. Health
education on malaria prevention and dangers of drug abuse should form part of
orientation lectures for all freshmen. University health centres should be
upgraded to provide basic antenatal care services.
PMID- 29333297
TI - Metronomic Chemotherapy in Triple-Negative Metastatic Breast Cancer: The Future
Is Now?
AB - Triple-negative breast cancer (TNBC) shows a very bad prognosis, even in early
stages of disease. Metronomic chemotherapy refers to the minimum biologically
effective dose of a chemotherapy agent given as a continuous dosing regimen with
no prolonged drug-free breaks that leads to antitumor activity. In the present
article, we review preclinical and clinical data of metronomic administration of
chemotherapy agents with or without biological agents in TNBC cell lines and
patients, contextually reporting data from the VICTOR-2 study in the subgroup of
patients with TNBC, in order to stimulate new ideas for the design of clinical
trials in this subset of patients.
PMID- 29333298
TI - Inability to Utilize Retrograde Cardioplegia due to a Persistent Left Superior
Vena Cava.
AB - A persistent left superior vena cava is a congenital abnormality that affects a
minority of the general population. While this finding is not hemodynamically
significant in all patients, failure to recognize the altered anatomy in any of
these patients can be consequential during procedures such as central venous
catheter placement, pacemaker/defibrillator wire placement, and use of retrograde
cardioplegia during cardiac surgery. We present a case of an intraoperative
diagnosis of a persistent left superior vena cava that altered the original plan
to arrest the heart using retrograde cardioplegia. Echocardiography was
instrumental in this diagnosis and avoided potentially inadequate myocardial
protection during cardiopulmonary bypass.
PMID- 29333299
TI - Ventricular Fibrillation following Varicella Zoster Myocarditis.
AB - Varicella-zoster virus (VZV) infection can rarely lead to serious cardiac
complications and life-threatening arrhythmias. We present a case of a 46-year
old male patient who developed VZV myocarditis and presented with recurrent
syncopal episodes followed by a cardiac arrest. He had a further collapse eight
years later, and cardiac magnetic resonance imaging (MRI) demonstrated mild mid
wall basal and inferolateral wall fibrosis. He was treated with an implantable
cardioverter defibrillator (ICD) and represented two years later with ICD shocks,
and interrogation of the device revealed ventricular fibrillation episodes. This
case demonstrates the life-threatening long-term sequelae of VZV myocarditis in
adults. We suggest that VZV myocarditis should be considered in all patients who
present with a syncopal event after VZV infection. In these patients, ICD
implantation is a potentially life-saving procedure.
PMID- 29333300
TI - Cyclic Nonrespiratory Pulse Pressure Oscillations Caused by Atrioventricular
Dissociation.
AB - Dynamic preload assessment tests, especially pulse pressure variation (PPV) and
stroke volume variation (SVV), are increasingly acknowledged in mechanically
ventilated patients as being predictors of fluid responsiveness. However, the
limitations of this method are often neglected or overlooked. One of the
prerequisites for PPV and SVV evaluation, in addition to intermittent positive
pressure ventilation, is a "regular heart rhythm," which may be an ambiguous
term. We present a case where, despite a regular (paced) rhythm, atrioventricular
dissociation was present and resulted in marked PPV elevation, which subsequently
disappeared once sinus rhythm returned. Our case indicates that PPV and SVV
should be interpreted with caution when atrioventricular dissociation is present.
PMID- 29333301
TI - A Case of Segmental Arterial Mediolysis Presenting as Mucosal Gastric Hematoma.
AB - Background: Although segmental arterial mediolysis (SAM) has been increasingly
recognized as arteriopathy and there are some case reports about SAM, it is still
very rare. It is characterized clinically by aneurysm, dissection, stenosis, and
occlusion within splanchnic arterial branches, causing intra-abdominal hemorrhage
or bowel ischemia. Mortality is as high as 50% in acute events. Case
Presentation: A 51-year-old man was referred to our hospital with hematemesis.
Gastroscopy revealed a submucosal-like tumor on the posterior wall of gastric
angle with ulceration. Computed tomography indicated a tumor measuring 65 * 50 mm
in the stomach, which was suspected to have invaded into the pancreas.
Significant hematemesis recurred; the patient developed shock and underwent
emergency distal gastrectomy, distal pancreatectomy, and splenectomy. The
pathology and the clinical course were compatible with SAM splenic artery rupture
causing retroperitoneal hemorrhage that penetrated into the stomach. After that
surgery, aneurysm of common hepatic artery ruptured and coil embolization was
performed. Conclusion: SAM is an important cause of intra-abdominal or
retroperitoneal hemorrhage in patients without underlying disease. SAM typically
presents as intra-abdominal hemorrhage, but, in this case, the retroperitoneal
hemorrhage penetrated into the stomach and it looked like a submucosal tumor.
PMID- 29333302
TI - A Mysterious DRESS Case: Autoimmune Enteropathy Associated with DRESS Syndrome.
AB - Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a rare but
potentially life-threatening cutaneous hypersensitivity reaction characterized by
extensive mucocutaneous eruption, fever, hematologic abnormalities, and extensive
organ involvement. Here, we present a case of a young woman with DRESS syndrome
following exposure to vancomycin with renal, cutaneous, and gastrointestinal
involvement. To the best of our knowledge, this is the first case description in
the literature of DRESS of the gastrointestinal tract with autoimmune
enteropathy.
PMID- 29333303
TI - Schinzel-Giedion Syndrome with Congenital Megacalycosis in a Turkish Patient:
Report of SETBP1 Mutation and Literature Review of the Clinical Features.
AB - Schinzel-Giedion syndrome (SGS) is a rare autosomal dominant disorder that
results in facial dysmorphism, multiple congenital anomalies, and an increased
risk of malignancy. Recently, using exome sequencing, de novo heterozygous
mutations in the SETBP1 gene have been identified in patients with SGS. Most
affected individuals do not survive after childhood because of the severity of
this disorder. Here, we report SETBP1 mutation confirmed by molecular analysis in
a case of SGS with congenital megacalycosis.
PMID- 29333304
TI - Synthetic Cannabinoid Abuse and a Rare Alpha-1-Antitrypsin Mutant Causing Acute
Fulminant Hepatitis: A Case Report and Review of the Literature.
AB - Synthetic cannabinoids (SCs) abuse is on the rise because they are easily
obtained over the counter; they are potent psychoactive compounds and routine
drug testing does not detect them. As their abuse is on the rise, so are their
detrimental side effects; however, the occurrence of acute hepatitis due to SCs
abuse has been reported only once before. In this case, testing revealed that the
patient was also heterozygous for alpha-1-antitrypsin (A-1-AT) with the phenotype
of PI*EM. This mutant phenotype has never been reported as a cause of A-1-AT
disease and the abuse of SCs in a patient with this phenotype has also never been
reported. This case illustrates the possible need to expand routine drug testing
for SCs and consider A-1-AT phenotyping in certain clinical scenarios.
PMID- 29333305
TI - A Rare Case of Transient Proximal Renal Tubular Acidosis in Pregnancy.
AB - Renal tubular acidosis (RTA) is a disorder that has improper function of renal
acid-base regulation and is rarely encountered during pregnancy. Currently, there
is no clear evidence on management and outcomes in patients with this condition.
We report a case of a previously healthy 23-year-old female at 30 weeks of
gestation who presented with proximal RTA and had spontaneous resolution of the
condition shortly after delivery.
PMID- 29333306
TI - Acute Cervical Dystonia Induced by Clebopride.
AB - Antidopaminergic drugs are known to induce extrapyramidal symptoms. Clebopride, a
dopamine antagonist, also can produce parkinsonism, tardive dyskinesia, tardive
dystonia, hemifacial dystonia, or oculogyric crisis; however, acute dystonic
reaction caused by clebopride has not been reported in adults. We report two
young men who experienced acute cervical dystonia within a few days of taking
clebopride. The patients recovered after discontinuation of the drug. Physicians
prescribing clebopride should be aware of the adverse effects of this drug.
PMID- 29333307
TI - Recurrent Cesarean Scar Ectopic Pregnancy Treated with Systemic Methotrexate.
AB - Cesarean scar pregnancy (CSP) is a rare event; however its incidence has been
rising due to the increasing rates of cesarean deliveries. The majority of cases
present with signs or symptoms requiring surgery, which often results in
hysterectomy. The recurrence of CSP is even rarer with only few cases which have
been reported. This is a report of recurrent cesarean scar ectopic pregnancy
(RCSP) that was promptly diagnosed and managed with only systemic methotrexate.
This was a 30-year-old woman, with a history of two prior cesarean deliveries
followed by a CSP, who presented at 5 weeks and 3 days of gestation for her first
prenatal visit. Transvaginal ultrasound revealed a RCSP. Her serum beta-human
chorionic gonadotropin (beta-hCG) level was 54,295 IU/L. The first CSP, which was
diagnosed at a later stage, was treated with uterine artery embolization and
systemic methotrexate leading to complete resolution within 10 weeks. The current
ectopic was treated with two doses of systemic methotrexate; her serum beta-hCG
reached undetectable levels within 7 weeks. Thus, patients with a history of
prior CSP should be carefully monitored with transvaginal ultrasound during
subsequent pregnancies to allow early diagnosis of RCSP, which could then be
treated conservatively.
PMID- 29333308
TI - Recurrent Gastrointestinal Stromal Tumors in the Imatinib Mesylate Era: Treatment
Strategies for an Incurable Disease.
AB - Introduction: Recurrence of gastrointestinal stromal tumors (GISTs) after
surgical resection and imatinib mesylate (IM) adjuvant therapy poses a
significant treatment challenge. We present the case of a patient who underwent
surgical resection after recurrence and review the current literature regarding
treatment. Case Presentation: A 58-year-old man with a large intra-abdominal
jejunal GIST was treated with complete surgical resection followed by IM. The
patient experienced disease recurrence 3.5 years later and underwent IM dose
escalation and reresection. Conclusion: Current strategies to treat recurrent
GIST include dose escalation, modifying adjuvant tyrosine kinase inhibitor
therapy, and surgery. High-level evidence will be required to better define the
combinatory roles of tyrosine kinase inhibitor therapy, guided by molecular
profiling, and surgery in the management of recurrent GIST.
PMID- 29333309
TI - Intraperitoneal Granulomas Unexpectedly Found during a Cesarean Delivery: A Late
Complication of Dropped Gallstones.
AB - Laparoscopic cholecystectomy is the treatment of choice for patients with
symptomatic cholelithiasis. Spillage of gallstones into the abdominal cavity
during laparoscopic cholecystectomy occurs in approximately one-third of cases.
Although retained gallstones remain asymptomatic, few cases may develop
complications. We report the case of a 29-year-old nulliparous woman presenting
with several hard nodules in the omentum, raising the possibility of a metastatic
disease. Histological examination demonstrated a bile-stained material and a
foreign body-type granulomatous response without neoplastic tissue. Our case
demonstrates an example of a complication resulting two years after a
laparoscopic cholecystectomy that was unexpectedly found during a cesarean
delivery. Pathologists should be aware of this entity to avoid interpretation
errors.
PMID- 29333310
TI - Hemiataxia: A Novel Presentation of Anti-NMDA Receptor Antibody Mediated
Encephalitis in an Adolescent.
AB - Anti-NMDA receptor antibody associated encephalitis as a cause of new-onset
neuropsychiatric manifestations in children and adults can represent a
significant diagnostic challenge for clinicians. Clinical signs often include
encephalopathy, new-onset psychosis, and movement phenomenon. Although orofacial
dyskinesias were initially identified as a characteristic movement phenomenon in
this type of encephalitis, an expanded range of abnormalities has recently been
reported, including isolated ataxia. We report a case of isolated hemiataxia in a
young adult with mild initial psychiatric manifestations. A personal and family
history of preceding neuropsychiatric symptoms produced diagnostic confusion and
resulted in a significant diagnostic and therapeutic delay. Our case confirms the
unilateral movement manifestations that have been emphasized in recent reports.
Additionally, it confirms the need for involvement of neurologic as well as
psychiatric services in the evaluation of such cases and emphasizes the
importance of the neurologic examination in presentations with an initial
psychiatric predominance.
PMID- 29333312
TI - Mesh Migration into the J-Pouch in a Patient with Post-Ulcerative Colitis
Colectomy: A Case Report and Literature Review.
AB - Mesh repair offers advantages like lower postsurgical pain and earlier return to
work. Thus, it has become a widely used treatment option. Here, we present the
first case report of a mesh migration into a J-pouch in a patient with history of
ulcerative colitis who underwent total abdominal colectomy with J-pouch and
ileoanal anastomosis and a subsequent laparoscopic ventral hernia repair with
mesh.
PMID- 29333311
TI - An Uncommon Case of Bilateral Breast Enlargement Diagnosed as Tumoral
Pseudoangiomatous Stromal Hyperplasia: Imaging and Pathological Findings.
AB - The incidence of reported pseudoangiomatous stromal hyperplasia (PASH), as well
as the variability and severity of clinical presentations, is increasing in the
literature. In parallel, several authors posit the need for an improved
classification of PASH to avoid possible variables associated with this
diagnosis. Here, we present a 25-year-old woman with PASH accompanied by severe
bilateral and symmetrical breasts enlargement, highlighting an uncommon clinical
presentation of PASH as much as the careful interdisciplinary review and
correlation of histology and all available imaging studies to confirm the
definitive diagnosis.
PMID- 29333313
TI - Retroperitoneal Necrotizing Fasciitis from Fournier's Gangrene in an
Immunocompromised Patient.
AB - Introduction: Necrotizing fasciitis (NF) is a devastating soft tissue disease
causing fulminant clinical deterioration, and extension into the retroperitoneum
has a high mortality rate. This disease process demands a strong clinical
suspicion for early identification which must be coupled with frequent wide
surgical debridements and intravenous antibiotics for improved outcomes. Various
clinical risk factors may render a weakness in the patient's immune status
including diabetes mellitus, chronic renal failure, obesity, and autoimmune
disorders, such as a human immunodeficiency virus (HIV) infection. Case Report: A
55-year-old male presented with hypotension requiring a large intravenous fluid
resuscitation and vasopressors. He was diagnosed with the human immunodeficiency
virus upon presentation. A computerized tomographic scan revealed air and fluid
in the perineum and pelvis, ascending into the retroperitoneum. Multiple surgical
debridements to his perineum, deep pelvic structures, and retroperitoneum were
completed. After colostomy placement, antibiotic administration, and wound care,
he was closed using split-thickness skin grafting. Conclusion: NF is a sinister
and fulminant disease requiring prompt diagnosis and surgical intervention. The
best chance for survival occurs with emergent surgical debridement and
appropriate intravenous antibiotics. While retroperitoneal NF is consistent with
uniformly poor outcomes, patients are best treated in an American Burn
Association-verified burn center.
PMID- 29333314
TI - A Case of Small Bowel Obstruction and Enterocutaneous Fistulation Resulting from
a Mesenteric Haematoma following Blunt Abdominal Trauma.
AB - A 23-year-old male with a history of previous abdominal surgery was involved in a
road traffic accident. He was discharged after initial assessment but represented
several days with small bowel obstruction secondary to a mesenteric haematoma. He
underwent resection and recovered well but represented later on the day of
discharge with a leaking surgical wound consistent with an enterocutaneous
fistula. This was managed conservatively and closed spontaneously after ten days.
This case serves to highlight that adhesions from previous surgery can tether the
small bowel causing mesenteric injury following blunt-force trauma. It also
demonstrates that postoperative ileus can result in an enterocutaneous fistula
that has the appearance of an anastomotic breakdown but which resolves more
rapidly.
PMID- 29333315
TI - Early Contextual Fear Memory Deficits in a Double-Transgenic Amyloid-beta
Precursor Protein/Presenilin 2 Mouse Model of Alzheimer's Disease.
AB - Presenilin 1 and presenilin 2 (PS1 and PS2) play a critical role in gamma
secretase-mediated cleavage of amyloid-beta precursor protein (APP) and the
subsequent generation of beta-amyloid peptides. The purpose of the present study
was to test whether PS2 mutation accelerates the onset of contextual fear memory
deficits in a mouse model of AD that expresses a mutation (K670N/M671L) of the
human APP with the Swedish mutation (Tg2576 mice). In the present study, an
APP/PS2 double-transgenic mouse model (PS2Tg2576) was generated by crossbreeding
transgenic mice carrying the human mutant PS2 (N141I) with Tg2576 mice.
Contextual fear conditioning was tested in PS2Tg2576 mice aged 3, 4, 6, and 10-12
months. PS2Tg2576 mice showed a tendency of lower freezing behavior as early as 3
months of age, but significant memory impairment was observed from the age of 4
months. The cognitive impairment was more prominent at ages of 6 and 10-12
months. In contrast, Tg2576 mice aged 3 and 4 months exhibited successful
acquisition of contextual fear learning, but Tg2576 mice aged 6 months or older
showed significantly impaired fear memory. These results show that PS2 mutation
significantly accelerates the onset of fear memory deficits in the APP AD model
mice.
PMID- 29333316
TI - Impact of Mezieres Rehabilitative Method in Patients with Parkinson's Disease: A
Randomized Controlled Trial.
AB - The aim of this study was to assess the efficacy of Mezieres method in improving
trunk flexibility of the back muscles and balance in patients with Parkinson's
disease (PD). Materials and Methods. Thirty-six patients were randomized into 2
groups: the Mezieres treatment group and the control group (home exercise group).
The primary outcome was the improvement in balance per the Berg Balance Scale
(BBS) and the trunk flexibility of the back for the anterior flexion trunk test.
Also, we evaluated pain, gait balance for the Functional Gait Assessment (FGA),
disease-related disability for the Modified Parkinson's Activity Scale and the
Unified Parkinson's Disease Rating Scale (UPDRS), the quality of life, and the
functional exercise capacity. All the measures were evaluated at baseline (T0),
at the end of the rehabilitative program (T1), and at the 12-week follow-up (T2).
Results. In the Mezieres group, the BBS (p < .001) and trunk flexion test (p <
.001) improved significantly at T1 and remained the same at T2. Between groups,
significant changes were reported in FGA (p = .027) and UPDRS Total (p = .007) at
T1 and in FGA (p = .03) at T2. Conclusion. The Mezieres approach is efficacious
in improving the flexibility of the trunk and balance in PD patients.
PMID- 29333318
TI - Evaluation of Global Genomic DNA Methylation in Human Whole Blood by Capillary
Electrophoresis UV Detection.
AB - Alterations in global DNA methylation are implicated in various
pathophysiological processes. The development of simple and quick, yet robust,
methods to assess DNA methylation is required to facilitate its measurement and
interpretation in clinical practice. We describe a highly sensitive and
reproducible capillary electrophoresis method with UV detection for the
separation and detection of cytosine and methylcytosine, after formic acid
hydrolysis of DNA extracted from human whole blood. Hydrolysed samples were dried
and resuspended with water and directly injected into the capillary without
sample derivatization procedures. The use of a run buffer containing 50 mmol/L
BIS-TRIS propane (BTP) phosphate buffer at pH 3.25 and 60 mmol/L sodium acetate
buffer at pH 3.60 (4 : 1, v/v) allowed full analyte identification within 11 min.
Precision tests indicated an elevated reproducibility with an interassay CV of
1.98% when starting from 2 MUg of the extracted DNA. The method was successfully
tested by measuring the DNA methylation degree both in healthy volunteers and in
reference calf thymus DNA.
PMID- 29333319
TI - Comparative Liquid Chromatographic Study for Concurrent Determination of
Canagliflozin and Metformin in Combined Tablets.
AB - New HPLC-UV method (method A), for simultaneous determination of metformin (MET)
and canagliflozin (CANA), was developed and compared to another novel UPLC-UV
method (method B) in their tablet combination. Concerning method A, isocratic
separation was done by C18 column (100 mm * 2.1 mm, 3 MUm) using methanol and
0.03 M phosphate buffer (75 : 25, v/v) at pH 3.2 as a mobile phase. Meanwhile,
chromatographic separation in method B was achieved via Hypersil(r) gold (50 mm *
2.1 mm, 1.9 MUm). Mobile phase was methanol and 0.03 M phosphate buffer at ratio
of 80 : 20 v/v. In both, detection was done at wavelength of 240 nm. Method A
showed satisfactory linearity results over 1-50 MUg.mL-1 and 0.5-100 MUg.mL-1,
while method B linearity was at 0.1-50 MUg.mL-1 and 0.25-100 MUg.mL-1 for CANA
and MET, respectively. In terms of accuracy and precision, method A accuracy was
99.81 +/- 0.73 and 99.37 +/- 0.54, while method B gave accuracy of 99.47 +/- 1.03
and 99.73 +/- 0.89 for CANA and MET, respectively. For precision, the % RSD was
found to be less than 2% for three concentrations analyzed three times. The two
methods are convenient for quality laboratories, yet the UPLC method offered the
advantage of shorter run times and higher sensitivity.
PMID- 29333317
TI - Phosphorylated alpha-Synuclein-Copper Complex Formation in the Pathogenesis of
Parkinson's Disease.
AB - Parkinson's disease is the second most important neurodegenerative disorder
worldwide. It is characterized by the presence of Lewy bodies, which are mainly
composed of alpha-synuclein and ubiquitin-bound proteins. Both the ubiquitin
proteasome system (UPS) and autophagy-lysosomal pathway (ALS) are altered in
Parkinson's disease, leading to aggregation of proteins, particularly alpha
synuclein. Interestingly, it has been observed that copper promotes the protein
aggregation process. Additionally, phosphorylation of alpha-synuclein along with
copper also affects the protein aggregation process. The interrelation among
alpha-synuclein phosphorylation and its capability to interact with copper, with
the subsequent disruption of the protein degradation systems in the
neurodegenerative process of Parkinson's disease, will be analyzed in detail in
this review.
PMID- 29333320
TI - Our recap for happy new year.
PMID- 29333321
TI - Periodontal wound healing following reciprocal autologous root transplantation in
class III furcation defects.
AB - Purpose: Furcation involvement in the molars is difficult to treat, and has been
recognized as a risk factor for tooth loss. Although periodontal regenerative
therapies, including guided tissue regeneration and various types of bone grafts,
have been applied to furcation defects, the effects of these treatments are
limited, especially in large class III furcation defects. The purpose of this
pilot study was to investigate the effect of reciprocal autologous root
transplantation on periodontal wound healing and regeneration in class III
furcation defects in dogs. Methods: Furcation defects (7 mm wide and 6 mm high)
were surgically created after root separation of the unilateral third and fourth
premolars in 4 dogs. Eight furcation defects were randomized to receive either
reciprocal autologous root transplantation (test) or no further treatment
(control). In the test group, the mesial and distal roots were transplanted into
the distal and mesial extraction sockets, respectively. The animals were
sacrificed 10 weeks after surgery for histologic evaluation. Results: The healing
pattern in the control group was characterized by extensive collapse of the flap
and limited periodontal regeneration. New bone formation in the test group
(3.56+/-0.57 mm) was significantly greater than in the control group (0.62+/-0.21
mm). Dense collagen fibers inserting into the residual cementum on the
transplanted root surfaces were observed in the test group. Slight ankylosis was
observed in 2 of the 4 specimens in the test group on the mesiodistal sides where
the root-planed surfaces faced the existing bone. Root resorption (RR) was
detected in both the control and test groups. Conclusions: Within the limits of
this study, it can be concluded that reciprocal autologous root transplantation
was effective for bone regeneration in class III furcation defects in dogs.
However, further studies are required to standardize the approach in order to
prevent unwanted RR prior to clinical application.
PMID- 29333322
TI - A randomized controlled clinical study of periodontal tissue regeneration using
an extracellular matrix-based resorbable membrane in combination with a
collagenated bovine bone graft in intrabony defects.
AB - Purpose: The purpose of this study was to investigate the feasibility of
regenerative therapy with a collagenated bone graft and resorbable membrane in
intrabony defects, and to evaluate the effects of the novel extracellular matrix
(ECM)-based membrane clinically and radiologically. Methods: Periodontal tissue
regeneration procedure was performed using an ECM-based resorbable membrane in
combination with a collagenated bovine bone graft in intrabony defects around the
teeth and implants. A novel extracellular matrix membrane (NEM) and a widely-used
membrane (WEM) were randomly applied to the test group and the control group,
respectively. Cone-beam computed tomography images were obtained on the day of
surgery and 6 months after the procedure. Alginate impressions were taken and
plaster models were made 1 week and 6 months postoperatively. Results: The
quantity of bone tissue, the dimensional changes of the surgically treated
intrabony defects, and the changes in width and height below the grafted bone
substitutes showed no significant difference between the test and control groups
at the 6-month examination. Conclusions: The use of NEM for periodontal
regeneration with a collagenated bovine bone graft showed similar clinical and
radiologic results to those obtained using WEM.
PMID- 29333323
TI - Alveolar ridge preservation with an open-healing approach using single-layer or
double-layer coverage with collagen membranes.
AB - Purpose: The aim of this prospective pilot study was to compare alveolar ridge
preservation (ARP) procedures with open-healing approach using a single-layer and
a double-layer coverage with collagen membranes using radiographic and clinical
analyses. Methods: Eleven molars from 9 healthy patients requiring extraction of
the maxillary or mandibular posterior teeth were included and allocated into 2
groups. After tooth extraction, deproteinized bovine bone mineral mixed with 10%
collagen was grafted into the socket and covered either with a double-layer of
resorbable non-cross-linked collagen membranes (DL group, n=6) or with a single
layer (SL group, n=5). Primary closure was not obtained. Cone-beam computed
tomography images were taken immediately after the ARP procedure and after a
healing period of 4 months before implant placement. Radiographic measurements
were made of the width and height changes of the alveolar ridge. Results: All
sites healed without any complications, and dental implants were placed at all
operated sites with acceptable initial stability. The measurements showed that
the reductions in width at the level 1 mm apical from the alveolar crest
(including the bone graft) were -1.7+/-0.5 mm in the SL group and -1.8+/-0.4 mm
in the DL group, and the horizontal changes in the other areas were also similar
in the DL and SL groups. The reductions in height were also comparable between
groups. Conclusions: Within the limitations of this study, single-layer and
double-layer coverage with collagen membranes after ARP failed to show
substantial differences in the preservation of horizontal or vertical dimensions
or in clinical healing. Thus, both approaches seem to be suitable for open
healing ridge preservation procedures.
PMID- 29333324
TI - Ridge preservation using basic fibroblast growth factor-2 and collagenated
biphasic calcium phosphate in beagle dogs.
AB - Purpose: The aim of this study was to evaluate volumetric and histologic changes
in edentulous alveolar ridge areas after ridge preservation using basic
fibroblast growth factor-2 (bFGF-2) in combination with collagenated biphasic
calcium phosphate (BCP). Methods: The experiments were performed in 6 adult male
beagle dogs. The following 3 groups were created: 1) ridge preservation with bFGF
2 and collagenated BCP (experimental group), 2) ridge preservation with
collagenated BCP (positive control group), and 3) a negative control group in
which no ridge preservation procedure was performed. Volumetric change analysis
was performed using an optical scanner and casts. Histological observations were
made using light microscopy. Results: After the initial swelling subsided, the
magnitude of the volumetric change in the experimental group and positive control
group was smaller than in the negative control group. In the experimental group,
a distinct trend was observed for the resorption of residual bone and collagen
fibers at 4 weeks and for more mature bone and faster healing at 12 weeks.
Conclusions: Based on the findings of the present study, bFGF-2 may be considered
for use as a therapeutic molecule in ridge preservation procedures.
PMID- 29333325
TI - Physicochemical characterization of porcine bone-derived grafting material and
comparison with bovine xenografts for dental applications.
AB - Purpose: The physicochemical properties of a xenograft are very important because
they strongly influence the bone regeneration capabilities of the graft material.
Even though porcine xenografts have many advantages, only a few porcine
xenografts are commercially available, and most of their physicochemical
characteristics have yet to be reported. Thus, in this work we aimed to
investigate the physicochemical characteristics of a porcine bone grafting
material and compare them with those of 2 commercially available bovine
xenografts to assess the potential of xenogenic porcine bone graft materials for
dental applications. Methods: We used various characterization techniques, such
as scanning electron microscopy, the Brunauer-Emmett-Teller adsorption method,
atomic force microscopy, Fourier-transform infrared spectroscopy, X-ray
diffraction, and others, to compare the physicochemical properties of xenografts
of different origins. Results: The porcine bone grafting material had relatively
high porosity (78.4%) and a large average specific surface area (SSA; 69.9 m2/g),
with high surface roughness (10-point average roughness, 4.47 um) and sub-100-nm
hydroxyapatite crystals on the surface. Moreover, this material presented a
significant fraction of sub-100-nm pores, with negligible amounts of residual
organic substances. Apart from some minor differences, the overall
characteristics of the porcine bone grafting material were very similar to those
of one of the bovine bone grafting material. However, many of these
morphostructural properties were significantly different from the other bovine
bone grafting material, which exhibited relatively smooth surface morphology with
a porosity of 62.0% and an average SSA of 0.5 m2/g. Conclusions: Considering that
both bovine bone grafting materials have been successfully used in oral surgery
applications in the last few decades, this work shows that the porcine-derived
grafting material possesses most of the key physiochemical characteristics
required for its application as a highly efficient xenograft material for bone
replacement.
PMID- 29333328
TI - Learning Tree-Structured Detection Cascades for Heterogeneous Networks of
Embedded Devices.
AB - In this paper, we present a new approach to learning cascaded classifiers for use
in computing environments that involve networks of heterogeneous and resource
constrained, low-power embedded compute and sensing nodes. We present a
generalization of the classical linear detection cascade to the case of tree
structured cascades where different branches of the tree execute on different
physical compute nodes in the network. Different nodes have access to different
features, as well as access to potentially different computation and energy
resources. We concentrate on the problem of jointly learning the parameters for
all of the classifiers in the cascade given a fixed cascade architecture and a
known set of costs required to carry out the computation at each node. To
accomplish the objective of joint learning of all detectors, we propose a novel
approach to combining classifier outputs during training that better matches the
hard cascade setting in which the learned system will be deployed. This work is
motivated by research in the area of mobile health where energy efficient real
time detectors integrating information from multiple wireless on-body sensors and
a smart phone are needed for real-time monitoring and the delivery of just-in
time adaptive interventions. We evaluate our framework on mobile sensor-based
human activity recognition and mobile health detector learning problems.
PMID- 29333326
TI - Evaluation of the periodontal regenerative properties of patterned human
periodontal ligament stem cell sheets.
AB - Purpose: The aim of this study was to determine the effects of patterned human
periodontal ligament stem cell (hPDLSC) sheets fabricated using a
thermoresponsive substratum. Methods: In this study, we fabricated patterned
hPDLSC sheets using nanotopographical cues to modulate the alignment of the cell
sheet. Results: The hPDLSCs showed rapid monolayer formation on various surface
pattern widths. Compared to cell sheets grown on flat surfaces, there were no
significant differences in cell attachment and growth on the nanopatterned
substratum. However, the patterned hPDLSC sheets showed higher periodontal
ligamentogenesis-related gene expression in early stages than the unpatterned
cell sheets. Conclusions: This experiment confirmed that patterned cell sheets
provide flexibility in designing hPDLSC sheets, and that these stem cell sheets
may be candidates for application in periodontal regenerative therapy.
PMID- 29333327
TI - Subcellular western blotting of single cells.
AB - Although immunoassays are the de facto standard for determining subcellular
protein localization in individual cells, antibody probe cross-reactivity and
fixation artifacts remain confounding factors. To enhance selectivity while
providing single-cell resolution, we introduce a subcellular western blotting
technique capable of separately assaying proteins in the 14 pL cytoplasm and 2 pL
nucleus of individual cells. To confer precision fluidic control, we describe a
passive multilayer microdevice that leverages the rapid transport times afforded
by miniaturization. After isolating single cells in microwells, we apply single
cell differential detergent fractionation to lyse and western blot the
cytoplasmic lysate, whereas the nucleus remains intact in the microwell.
Subsequently, we lyse the intact nucleus and western blot the nuclear lysate. To
index each protein analysis to the originating subcellular compartment, we
utilize bi-directional electrophoresis, a multidimensional separation that assays
the lysate from each compartment in a distinct region of the separation axis.
Single-cell bi-directional electrophoresis eliminates the need for semi
subjective image segmentation algorithms required in immunocytochemistry. The
subcellular, single-cell western blot is demonstrated for six targets per cell,
and successfully localizes spliceosome-associated proteins solubilized from large
protein and RNA complexes, even for closely sized proteins (a 7 kDa difference).
Measurement of NF-kappaB translocation dynamics in unfixed cells at 15-min
intervals demonstrates reduced technical variance compared with
immunofluorescence. This chemical cytometry assay directly measures the
nucleocytoplasmic protein distribution in individual unfixed cells, thus
providing insight into protein signaling in heterogeneous cell populations.
PMID- 29333329
TI - Stable Pd-Doped Ceria Structures for CH4 Activation and CO Oxidation.
AB - Doping CeO2 with Pd atoms has been associated with catalytic CO oxidation, but
current surface models do not allow CO adsorption. Here, we report a new
structure of Pd-doped CeO2(111), in which Pd adopts a square planar configuration
instead of the previously assumed octahedral configuration. Oxygen removal from
this doped structure is favorable. The resulting defective Pd-doped CeO2 surface
is active for CO oxidation and is also able to cleave the first C-H bond in
methane. We show how the moderate CO adsorption energy and dynamic features of
the Pd atom upon CO adsorption and CO oxidation contribute to a low-barrier
catalytic cycle for CO oxidation. These structures, which are also observed for
Ni and Pt, can lead to a more open coordination environment around the doped
transition-metal center. These thermally stable structures are relevant to the
development of single-atom catalysts.
PMID- 29333330
TI - Amorphous Cobalt Vanadium Oxide as a Highly Active Electrocatalyst for Oxygen
Evolution.
AB - The water-splitting reaction provides a promising mechanism to store renewable
energies in the form of hydrogen fuel. The oxidation half-reaction, the oxygen
evolution reaction (OER), is a complex four-electron process that constitutes an
efficiency bottleneck in water splitting. Here we report a highly active OER
catalyst, cobalt vanadium oxide. The catalyst is designed on the basis of a
volcano plot of metal-OH bond strength and activity. The catalyst can be
synthesized by a facile hydrothermal route. The most active pure-phase material
(a-CoVO x ) is X-ray amorphous and provides a 10 mA cm-2 current density at an
overpotential of 347 mV in 1 M KOH electrolyte when immobilized on a flat
substrate. The synthetic method can also be applied to coat a high-surface-area
substrate such as nickel foam. On this three-dimensional substrate, the a-CoVO x
catalyst is highly active, reaching 10 mA cm-2 at 254 mV overpotential, with a
Tafel slope of only 35 mV dec-1. This work demonstrates a-CoVO x as a promising
electrocatalyst for oxygen evolution and validates M-OH bond strength as a
practical descriptor in OER catalysis.
PMID- 29333331
TI - Single-impulse Panoramic Photoacoustic Computed Tomography of Small-animal Whole
body Dynamics at High Spatiotemporal Resolution.
AB - Imaging of small animals has played an indispensable role in preclinical research
by providing high dimensional physiological, pathological, and phenotypic
insights with clinical relevance. Yet pure optical imaging suffers from either
shallow penetration (up to ~1-2 mm) or a poor depth-to-resolution ratio (~1/3),
and non-optical techniques for whole-body imaging of small animals lack either
spatiotemporal resolution or functional contrast. Here, we demonstrate that
standalone single-impulse photoacoustic computed tomography (SIP-PACT) mitigates
these limitations by combining high spatiotemporal resolution (125-um in-plane
resolution, 50 us / frame data acquisition and 50-Hz frame rate), deep
penetration (48-mm cross-sectional width in vivo), anatomical, dynamical and
functional contrasts, and full-view fidelity. By using SIP-PACT, we imaged in
vivo whole-body dynamics of small animals in real time and obtained clear sub
organ anatomical and functional details. We tracked unlabeled circulating
melanoma cells and imaged the vasculature and functional connectivity of whole
rat brains. SIP-PACT holds great potential for both pre-clinical imaging and
clinical translation.
PMID- 29333333
TI - 'Her body [was] like a hard-worked machine': Women's work and disability in
coalfields literature, 1880-1950.
AB - This essay considers the representation of women's work and disability in British
coalfields literature in the period 1880-1950. Industrial settings are a rich
source for literature concerned with bodily health, injury and disability and
offer insights into the gendering of the working body whether male or female.
Situating this largely realist body of novels, stories and plays in its
historical context, this article will focus on intersections between work, class
and gender. It shows how the vital, but unpaid, work of women in domestic labour
was depicted as an extension of the industrial machine, which had clear
consequences in terms of high mortality and morbidity rates amongst women.
PMID- 29333334
TI - The Effect of the 2012 ASCCP Consensus Guideline for Abnormal Cervical Cytology
on Resident Colposcopy Training.
AB - The primary objective was to determine the theoretical number of colposcopies at
a resident clinic if the 2012 American Society for Colposcopy and Cervical
Pathology (ASCCP) guidelines were applied. The secondary objective was to
determine the actual number of colposcopies before and after the ASCCP
guidelines. This was a two-part descriptive study. The first part applied the
2012 ASCCP guidelines to all pre-guideline colposcopy cases at a single resident
clinic. These theoretical results were then compared to the actual number of
colposcopies. The second part compared the actual number of colposcopies during
the one-year time period before and after the guidelines. Chi-Square tests and
Fisher's Exact tests were used to examine the association of categorical
variables. Seventy-three colposcopies were performed during the pre-guideline
period. After applying the 2012 ASCCP guidelines, 52.1% would not have been
indicated, resulting in 35 colposcopies. The largest reductions would have
occurred in patients with low grade cytologic abnormalities. Applying the new
guidelines, patients 24 years and younger would have been less likely than
patients ages 25 to 64 to require colposcopy (P<.001). Fifty-eight indicated
colposcopies were actually performed during the post-guideline period. While
there was a decrease in the number of colposcopies performed post-guidelines, the
decrease was not as dramatic as expected. From a training standpoint, as
indications for colposcopy decrease, fewer training opportunities are available
for residents. In particular, residents will have less experience evaluating low
grade cytologic abnormalities in younger women.
PMID- 29333335
TI - Recommendations for Contraception: Examining the Role of Patients' Age and Race.
AB - The literature suggests that women of different races are more or less likely to
use certain contraceptive methods and patient race can influence which
contraceptive recommendations a provider makes. To explore whether health care
providers treat individuals of different races differently, we conducted a
preliminary investigation on whether medical students recommended different
contraceptive methods for hypothetical patients presenting with the same clinical
features who only varied by race. Third- and fourth-year medical students (n=103)
at the University of Hawai'i completed an online survey. Students read case
studies about a 23-year-old and 36-year-old patient and then made contraceptive
recommendations. All students reviewed the same scenarios, with the exception of
the patient's name which was randomly assigned to represent one of five
racial/ethnic groups (White, Chinese, Filipina, Native Hawaiian, and
Micronesian). Recommendations were analyzed using chi2 tests and bivariate
logistic regressions. For the younger patient, students were most likely to
recommend intrauterine devices (IUDs), followed by the contraceptive pill and
Etonogestrel implant; recommendations did not differ by race/ethnicity (P = .91).
For the older patient, students were most likely to recommend IUDs or
sterilization, and Micronesian women were more likely to receive sterilization
recommendations compared to White women (60% versus 27%, P = .04). In summary,
contraceptive recommendations, specifically the frequency of recommending
sterilization varied by race. Our findings add to the literature exploring the
role of a patient's race/ethnicity on recommendations for contraception and
highlights the need for more studies exploring the etiology of health care
disparities.
PMID- 29333336
TI - Medical School Hotline: School of Medicine Departments - Year in Review 2017,
Part 1.
PMID- 29333332
TI - Next Generation Tissue Engineering of Orthopedic Soft Tissue-to-Bone Interfaces.
AB - Soft tissue-to-bone interfaces are complex structures that consist of gradients
of extracellular matrix materials, cell phenotypes, and biochemical signals.
These interfaces, called entheses for ligaments, tendons, and the meniscus, are
crucial to joint function, transferring mechanical loads and stabilizing
orthopedic joints. When injuries occur to connected soft tissue, the enthesis
must be re-established to restore function, but due to structural complexity,
repair has proven challenging. Tissue engineering offers a promising solution for
regenerating these tissues. This prospective review discusses methodologies for
tissue engineering the enthesis, outlined in three key design inputs: materials
processing methods, cellular contributions, and biochemical factors.
PMID- 29333337
TI - Insights in Public Health: Stepping Up Vector Control's Program Capacity To
Prevent Arboviral Disease Transmission in Hawai'i.
PMID- 29333339
TI - Time multiplexed deep reactive ion etching of germanium and silicon-A comparison
of mechanisms and application to x-ray optics.
AB - Although the mechanisms of deep reactive ion etching (DRIE) of silicon have been
reported extensively, very little by comparison has been discussed concerning
DRIE of germanium. By directly comparing silicon and germanium etching in a time
multiplexed DRIE process, the authors extract significant differences in etch
mechanisms from a design of experiment and discuss how these differences are
relevant to the design and fabrication of silicon and germanium collimating
channel array x-ray optics. The differences are illuminated by characteristics
such as reactive ion etching (RIE)-lag, aspect ratio dependent etching, and
sidewall passivation. Specifically, the authors demonstrate the more severe
nature of RIE-lag in germanium, especially at aspect ratios exceeding 13:1. In
addition, the differences in the profile evolution between silicon and germanium
are shown to be a result of differences in sidewall passivation. There is also a
correlation between the different sidewall passivation and the inherent lack of
scalloping in the case of germanium DRIE.
PMID- 29333340
TI - Examining differences in HPV awareness and knowledge and HPV vaccine awareness
and acceptability between U.S. Hispanic and island Puerto Rican women.
AB - Background: In 2015, only 42% of Puerto Rican (PR) girls aged 13-17 and 44% of
U.S. Hispanic girls aged 13-17 were vaccinated with all three Human
Papillomavirus (HPV) vaccine doses; These percentages were far lower than the
Healthy People 2020 goal of 80% of girls aged 13-15 the Healthy People 2020 goal
of 80%. The purpose of this study was to examine potential differences in HPV
awareness and knowledge and HPV vaccine awareness and acceptability between a
population-based sample of U.S. Hispanic and island Puerto Rican women. Methods:
We restricted our analyses to female respondents from the Health Information
National Trends Survey (HINTS) 2007 (n=375; U.S. Hispanic) and HINTS Puerto Rico
2009 (n=417; PR). Using the Wald chi-square test, we assessed if there were
significant differences in HPV awareness and knowledge and HPV vaccine awareness
and acceptability between U.S. Hispanic and island PR women. We then utilized
logistic or multinomial regression to control for covariates on significant
outcomes. Results: Both groups of Hispanic women were highly knowledgeable that
HPV causes cancer (89.2% in both samples) and that HPV is a sexually transmitted
infection (78.1% [U.S. Hispanics] and 84.7% [PR]). Less than 10% of both groups
recognized that HPV can clear on its own without treatment. Island PR women had
significantly higher HPV vaccine awareness (66.9% vs. 61.0%; Wald X2 F(1, 97) =
16.03, p < .001) and were more accepting of the HPV vaccine for a real or
hypothetical daughter, compared to U.S. Hispanic women (74.8% vs. 56.1%; Wald X2
F(2, 96) = 7.18, p < .001). However, after controlling for sociodemographic
variables and survey group, there was no longer a difference between the two
groups of women and HPV vaccine awareness (AOR = .53; 95% CI = .23, 1.24).
Moreover, after controlled analysis, island PR women were significantly less
likely to have their hypothetical daughter get the HPV vaccine, compared to U.S.
Hispanic women (AOR = 0.26; 95% CI = .08, .81). Conclusions: Future research
focused on factors contributing to differences and similarities in HPV knowledge
and awareness and HPV vaccine awareness and acceptability between these two
groups of Hispanic women is warranted. Findings may assist in developing health
education programs and media to promote HPV vaccination among both groups.
PMID- 29333341
TI - Preventive effects of Salvia officinalis leaf extract on insulin resistance and
inflammation in a model of high fat diet-induced obesity in mice that responds to
rosiglitazone.
AB - Background: Salvia officinalis (sage) is a native plant to the Mediterranean
region and has been used for a long time in traditional medicine for various
diseases. We investigated possible anti-diabetic, anti-inflammatory and anti
obesity effects of sage methanol (MetOH) extract in a nutritional mouse model of
obesity, inflammation and insulin resistance, as well as its effects on lipolysis
and lipogenesis in 3T3-L1 cells. Methods: Diet-induced obese (DIO) mice were
treated for five weeks with sage methanol extract (100 and 400 mg kg-1/day bid),
or rosiglitazone (3 mg kg-1/day bid), as a positive control. Energy expenditure,
food intake, body weight, fat mass, liver glycogen and lipid content were
evaluated. Blood glucose, and plasma levels of insulin, lipids leptin and pro-
and anti-inflammatory cytokines were measured throughout the experiment. The
effects of sage MetOH extract on lipolysis and lipogenesis were tested in vitro
in 3T3-L1 cells. Results: After two weeks of treatment, the lower dose of sage
MetOH extract decreased blood glucose and plasma insulin levels during an oral
glucose tolerance test (OGTT). An insulin tolerance test (ITT), performed at day
29 confirmed that sage improved insulin sensitivity. Groups treated with low dose
sage and rosiglitazone showed very similar effects on OGTT and ITT. Sage also
improved HOMA-IR, triglycerides and NEFA. Treatment with the low dose increased
the plasma levels of the anti-inflammatory cytokines IL-2, IL-4 and IL-10 and
reduced the plasma level of the pro-inflammatory cytokines IL-12, TNF-alpha, and
KC/GRO. The GC analysis revealed the presence of two PPARs agonist in sage MetOH
extract. In vitro, the extract reduced in a dose-related manner the accumulation
of lipid droplets; however no effect on lipolysis was observed. Conclusions: Sage
MetOH extract at low dose exhibits similar effects to rosiglitazone. It improves
insulin sensitivity, inhibits lipogenesis in adipocytes and reduces inflammation
as judged by plasma cytokines. Sage presents an alternative to pharmaceuticals
for the treatment of diabetes and associated inflammation.
PMID- 29333342
TI - Is there a link between aging and microbiome diversity in exceptional mammalian
longevity?
AB - A changing microbiome has been linked to biological aging in mice and humans,
suggesting a possible role of gut flora in pathogenic aging phenotypes. Many bat
species have exceptional longevity given their body size and some can live up to
ten times longer than expected with little signs of aging. This study explores
the anal microbiome of the exceptionally long-lived Myotis myotis bat,
investigating bacterial composition in both adult and juvenile bats to determine
if the microbiome changes with age in a wild, long-lived non-model organism,
using non-lethal sampling. The anal microbiome was sequenced using metabarcoding
in more than 50 individuals, finding no significant difference between the
composition of juvenile and adult bats, suggesting that age-related microbial
shifts previously observed in other mammals may not be present in Myotis myotis.
Functional gene categories, inferred from metabarcoding data, expressed in the M.
myotis microbiome were categorized identifying pathways involved in metabolism,
DNA repair and oxidative phosphorylation. We highlight an abundance of
'Proteobacteria' relative to other mammals, with similar patterns compared to
other bat microbiomes. Our results suggest that M. myotis may have a relatively
stable, unchanging microbiome playing a role in their extended 'health spans'
with the advancement of age, and suggest a potential link between microbiome and
sustained, powered flight.
PMID- 29333343
TI - Resounding failure to replicate links between developmental language disorder and
cerebral lateralisation.
AB - Background: It has been suggested that failure to establish cerebral
lateralisation may be related to developmental language disorder (DLD). There has
been weak support for any link with handedness, but more consistent reports of
associations with functional brain lateralisation for language. The consistency
of lateralisation across different functions may also be important. We aimed to
replicate previous findings of an association between DLD and reduced laterality
on a quantitative measure of hand preference (reaching across the midline) and on
language laterality assessed using functional transcranial Doppler ultrasound
(fTCD). Methods: From a sample of twin children aged from 6;0 to 11;11 years, we
identified 107 cases of DLD and 156 typically-developing comparison cases for
whom we had useable data from fTCD yielding a laterality index (LI) for language
function during an animation description task. Handedness data were also
available for these children. Results: Indices of handedness and language
laterality for this twin sample were similar to those previously reported for
single-born children. There were no differences between the DLD and TD groups on
measures of handedness or language lateralisation, or on a categorical measure of
consistency of left hemisphere dominance. Contrary to prediction, there was a
greater incidence of right lateralisation for language in the TD group (19.90%)
than the DLD group (9.30%), confirming that atypical laterality is not
inconsistent with typical language development. We also failed to replicate
associations between language laterality and language test scores. Discussion and
Conclusions: Given the large sample studied here and the range of measures, we
suggest that previous reports of atypical manual or language lateralisation in
DLD may have been false positives.
PMID- 29333344
TI - The old and the new plankton: ecological replacement of associations of mollusc
plankton and giant filter feeders after the Cretaceous?
AB - Owing to their great diversity and abundance, ammonites and belemnites
represented key elements in Mesozoic food webs. Because of their extreme
ontogenetic size increase by up to three orders of magnitude, their position in
the food webs likely changed during ontogeny. Here, we reconstruct the number of
eggs laid by large adult females of these cephalopods and discuss developmental
shifts in their ecologic roles. Based on similarities in conch morphology, size,
habitat and abundance, we suggest that similar niches occupied in the Cretaceous
by juvenile ammonites and belemnites were vacated during the extinction and later
partially filled by holoplanktonic gastropods. As primary consumers, these
extinct cephalopod groups were important constituents of the plankton and a
principal food source for planktivorous organisms. As victims or, respectively,
profiteers of this case of ecological replacement, filter feeding chondrichthyans
and cetaceans likely filled the niches formerly occupied by large pachycormid
fishes during the Jurassic and Cretaceous.
PMID- 29333345
TI - Ontogeny reversal and phylogenetic analysis of Turritopsis sp.5 (Cnidaria,
Hydrozoa, Oceaniidae), a possible new species endemic to Xiamen, China.
AB - Ontogeny reversal, as seen in some cnidarians, is an unprecedented phenomenon in
the animal kingdom involving reversal of the ordinary life cycle. Three species
of Turritopsis have been shown to be capable of inverted metamorphosis, a process
in which the pelagic medusa transforms back into a juvenile benthic polyp stage
when faced with adverse conditions. Turritopsis sp.5 is a species of Turritopsis
collected from Xiamen, China which presents a similar ability, being able to
reverse its life cycle if injured by mechanical stress. Phylogenetic analysis
based on both 16S rDNA and cytochrome c oxidase subunit I (COI) genetic barcodes
shows that Turritopsis sp.5 is phylogenetically clustered in a clade separate
from other species of Turritopsis. The genetic distance between T. sp.5 and the
Japanese species T. sp.2 is the shortest, when measured by the Kimura 2-Parameter
metric, and the distance to the New Zealand species T. rubra is the largest. An
experimental assay on the induction of reverse development in this species was
initiated by cutting medusae into upper and lower parts. We show, for the first
time, that the two dissected parts have significantly different potentials to
transform into polyps. Also, a series of morphological changes of the reversed
life cycle can be recognised, including medusa stage, contraction stage I,
contraction stage II, cyst, cyst with stolons, and polyp. The discovery of
species capable of reverse ontogeny caused by unfavorable conditions adds to the
available systems with which to study the cell types that contribute to the
developmental reversal and the molecular mechanisms of the directional
determination of ontogeny.
PMID- 29333346
TI - Boundaries in ground beetle (Coleoptera: Carabidae) and environmental variables
at the edges of forest patches with residential developments.
AB - Background: Few studies of edge effects on wildlife objectively identify habitat
edges or explore non-linear responses. In this paper, we build on ground beetle
(Coleoptera: Carabidae) research that has begun to address these domains by using
triangulation wombling to identify boundaries in beetle community structure and
composition at the edges of forest patches with residential developments. We
hypothesized that edges are characterized by boundaries in environmental
variables that correspond to marked discontinuities in vegetation structure
between maintained yards and forest. We expected environmental boundaries to be
associated with beetle boundaries. Methods: We collected beetles and measured
environmental variables in 200 m by 200 m sampling grids centered at the edges of
three forest patches, each with a rural, suburban, or urban context, in
Charlotte, North Carolina, USA. We identified boundaries within each grid at two
spatial scales and tested their significance and overlap using boundary
statistics and overlap statistics, respectively. We complemented boundary
delineation with k-means clustering. Results: Boundaries in environmental
variables, such as temperature, grass cover, and leaf litter depth, occurred at
or near the edges of all three sites, in many cases at both scales. The beetle
variables that exhibited the most pronounced boundary structure in relation to
edges were total species evenness, generalist abundance, generalist richness,
generalist evenness, and Agonum punctiforme abundance. Environmental and beetle
boundaries also occurred within forest patches and residential developments,
indicating substantial localized spatial variation on either side of edges.
Boundaries in beetle and environmental variables that displayed boundary
structure at edges significantly overlapped, as did boundaries on either side of
edges. The comparison of boundaries and clusters revealed that boundaries formed
parts of the borders of patches of similar beetle or environmental condition.
Discussion: We show that edge effects on ground beetle community structure and
composition and environmental variation at the intersection of forest patches and
residential developments can be described by boundaries and that these boundaries
overlap in space. However, our results also highlight the complexity of edge
effects in our system: environmental boundaries were located at or near edges
whereas beetle boundaries related to edges could be spatially disjunct from them;
boundaries incompletely delineated edges such that only parts of edges were well
described by sharp transitions in beetle and/or environmental variables; and the
occurrence of boundaries related to edges was apparently influenced by individual
property management practices, site-specific characteristics such as development
geometry, and spatial scale.
PMID- 29333347
TI - Beyond harm's reach? Submersion of river turtle nesting areas and implications
for restoration actions after Amazon hydropower development.
AB - The global expansion of energy demands combined with abundant rainfall, large
water volumes and high flow in tropical rivers have led to an unprecedented
expansion of dam constructions in the Amazon. This expansion generates an urgent
need for refined approaches to river management; specifically a move away from
decision-making governed by overly generalized guidelines. For the first time we
quantify direct impacts of hydropower reservoir establishment on an Amazon fresh
water turtle. We conducted surveys along 150 km of rivers upstream of a new dam
construction during the low water months that correspond to the nesting season of
Podocnemis unifilis in the study area. Comparison of nest-areas before (2011,
2015) and after (2016) reservoir filling show that reservoir impacts extend 13%
beyond legally defined limits. The submerged nesting areas accounted for a total
of 3.8 ha of nesting habitat that was inundated as a direct result of the
reservoir filling in 2016. Our findings highlight limitations in the development
and implementation of existing Brazilian environmental impact assessment process.
We also propose potential ways to mitigate the negative impacts of dams on
freshwater turtles and the Amazonian freshwater ecosystems they inhabit.
PMID- 29333348
TI - A new species of Cretalamna sensu stricto (Lamniformes, Otodontidae) from the
Late Cretaceous (Santonian-Campanian) of Alabama, USA.
AB - Decades of collecting from exposures of the Upper Cretaceous Tombigbee Sand
Member of the Eutaw Formation and Mooreville Chalk in Alabama, USA has produced
large numbers of isolated Cretalamna (sensu stricto) teeth. Many of these teeth
had formerly been assigned to the extinct Late Cretaceous shark Cretalamna
appendiculata (Agassiz, 1843), a taxon that is now considered largely restricted
to the Turonian of Europe. Recent studies have shed light on the diversity of
Late Cretaceous Cretalamna (s.s.) taxa, and here we recognize a new species from
Alabama, Cretalamna bryanti. The teeth of C. bryanti sp. nov. appear aligned with
the members of the Cretalamna borealis species group, but can be distinguished
from these other species by a combination of the following: anterior teeth with a
more pronounced and triangular lingual root protuberance, broader triangular
cusp, and a taller root relative to the height of the crown; anteriorly situated
lateroposterior teeth have a distally inclined or hooked main cusp and more than
one pair of lateral cusplets; and lateroposterior teeth have a strong distally
hooked main cusp and a root that is largely symmetrical in basal view. At
present, C. bryanti sp. nov. is stratigraphically confined to the
Santonian/Campanian Dicarinella asymetrica Sigal, 1952 and Globotruncanita
elevata Brotzen, 1934 Planktonic Foraminiferal Zones within the Tombigbee Sand
Member of the Eutaw Formation and Mooreville Chalk, and teeth have been collected
from only four counties in central and western Alabama. The recognition of C.
bryanti sp. nov. in Alabama adds to our knowledge on the diversity and
distribution of Late Cretaceous otodontids in the region.
PMID- 29333349
TI - Annual and spatial variation in composition and activity of terrestrial mammals
on two replicate plots in lowland forest of eastern Ecuador.
AB - Terrestrial mammals are important components of lowland forests in Amazonia (as
seed dispersal agents, herbivores, predators) but there are relatively few
detailed studies from areas that have not been affected by human activities
(e.g., hunting, logging). Yet, such information is needed to evaluate effects of
humans elsewhere. We used camera traps to sample medium to large-sized
terrestrial mammals at a site in lowland forests of eastern Ecuador, one of the
most biologically rich areas in the world. We deployed cameras on two study plots
in terra firme forest at Tiputini Biodiversity Station. Sixteen cameras were
arranged 200 m apart in a 4 * 4 grid on each plot. Cameras were operated for 60
days in January-March, 2014-2017, for a total of 3,707 and 3,482 trap-days on the
two plots (Harpia, Puma). A total of 28 species were recorded; 26 on Harpia and
25 on Puma. Number of species recorded each year was slightly greater on Harpia
whereas overall capture rates (images/100 trap-days) were higher on Puma.
Although most species were recorded on each plot, differences in capture rates
meant that yearly samples on a given plot were more similar to each other than to
samples on the other plot. Images of most species showed a clumped distribution
pattern on each plot; Panthera onca was the only species that did not show a
clumped distribution on either plot. Images at a given camera location showed no
evidence of autocorrelation with numbers of images at nearby camera locations,
suggesting that species were responding to small-scale differences in habitat
conditions. A redundancy analysis showed that environmental features within 50 or
100 m of camera locations (e.g., elevation, variation in elevation, slope,
distance to streams) accounted for significant amounts of variation in
distribution patterns of species. Composition and relative importance based on
capture rates were very similar to results from cameras located along trails at
the same site; similarities decreased at increasing spatial scales based on
comparisons with results from other sites in Ecuador and Peru.
PMID- 29333350
TI - Scale-up of a Luminescent Solar Concentrator-Based Photomicroreactor via
Numbering-up.
AB - The use of solar energy to power chemical reactions is a long-standing dream of
the chemical community. Recently, visible-light-mediated photoredox catalysis has
been recognized as the ideal catalytic transformation to convert solar energy
into chemical bonds. However, scaling photochemical transformations has been
extremely challenging due to Bouguer-Lambert-Beer law. Recently, we have
pioneered the development of luminescent solar concentrator photomicroreactors
(LSC-PMs), which display an excellent energy efficiency. These devices harvest
solar energy, convert the broad solar energy spectrum to a narrow-wavelength
region, and subsequently waveguide the re-emitted photons to the reaction
channels. Herein, we report on the scalability of such LSC-PMs via a numbering-up
strategy. Paramount in our work was the use of molds that were fabricated via 3D
printing. This allowed us to rapidly produce many different prototypes and to
optimize experimentally key design aspects in a time-efficient fashion. Reactors
up to 32 parallel channels have been fabricated that display an excellent flow
distribution using a bifurcated flow distributor (standard deviations below 10%).
This excellent flow distribution was crucial to scale up a model reaction
efficiently, displaying yields comparable to those obtained in a single-channel
device. We also found that interchannel spacing is an important and unique design
parameter for numbered-up LSC-PMs, which influences greatly the photon flux
experienced within the reaction channels.
PMID- 29333351
TI - Understanding the Effect of the Dianhydride Structure on the Properties of
Semiaromatic Polyimides Containing a Biobased Fatty Diamine.
AB - In this work we report the effect of the hard block dianhydride structure on the
overall properties of partially biobased semiaromatic polyimides. For the study,
four polyimides were synthesized using aliphatic fatty dimer diamine (DD1) as the
soft block and four different commercially available aromatic dianhydrides as the
hard block: 4,4'-(4,4'-isopropylidenediphenoxy) bis(phthalic anhydride) (BPADA),
4,4'-oxidiphthalic anhydride (ODPA), 4,4'-(Hexafluoroisopropylidene) diphthalic
anhydride (6FDA), and 3,3',4,4'-biphenyltetracarboxylic dianhydride (BPDA). The
polymers synthesized were fully organo-soluble thermoplastic branched polyimides
with glass transition temperatures close to room temperature. The detailed
analysis took into account several aspects of the dianhydrides structure
(planarity, rigidity, bridging group between the phtalimides, and electronic
properties) and related them to the results obtained by differential scanning
calorimetry, rheology, fluorescence and broadband dielectric spectroscopy.
Moreover, the effects of physical parameters (crystallization and electronic
interactions) on the relaxation behavior are discussed. Despite the presence of
the bulky branched soft block given by the dimer diamine, all polyimides showed
intermolecular charge transfer complexes, whose extent depends on the electronic
properties of the dianhydride hard block. Furthermore, the results showed that
polyimides containing flexible and bulky hard blocks turned out fully amorphous
while the more rigid dianhydride (BPDA) led to a nanophase separated morphology
with low degree of crystallinity resulting in constrained segmental relaxation
with high effect on its mechanical response with the annealing time. This work
represents the first detailed report on the development and characterization of
polyimides based on a biobased fatty dimer diamine. The results highlight the
potential of polymer property design by controlled engineering of the aromatic
dianhydride blocks.
PMID- 29333352
TI - Smartphone-Based Point-of-Care Urinalysis Under Variable Illumination.
AB - Urine tests are performed by using an off-the-shelf reference sheet to compare
the color of test strips. However, the tabular representation is difficult to use
and more prone to visual errors, especially when the reference color-swatches to
be compared are spatially apart. Thus, making it is difficult to distinguish
between the subtle differences of shades on the reagent pads. This manuscript
represents a new arrangement of reference arrays for urine test strips
(urinalysis). Reference color swatches are grouped in a doughnut chart,
surrounding each reagent pad on the strip. The urine test can be evaluated using
naked eye by referring to the strip with no additional sheet necessary. Along
with this new strip, an algorithm for smartphone based application is also
proposed as an alternative to deliver diagnostic results. The proposed
colorimetric detection method evaluates the captured image of the strip, under
various color spaces and evaluates ten different tests for urine. Thus, the
proposed system can deliver results on the spot using both naked eye and
smartphone. The proposed scheme delivered accurate results under various
environmental illumination conditions without any calibration requirements,
exhibiting performances suitable for real-life applications and an ease for a
common user.
PMID- 29333353
TI - Spine Stereotactic Body Radiation Therapy Residual Setup Errors and Intra
Fraction Motion Using the Stereotactic X-Ray Image Guidance Verification System.
AB - Purpose: To determine the precision of our institution's current immobilization
devices for spine SBRT, ultimately leading to recommendations for appropriate
planning margins. Methods: We identified 12 patients (25 treatments) with spinal
metastasis treated with spine Stereotactic Body Radiation Therapy (SBRT). The
Body-FIX system was used as immobilization device for thoracic (T) and lumbar (L)
spine lesions. The head and shoulder mask system was used as immobilization
device for cervical (C) spine lesions. Initial patient setup used the infrared
positioning system with body markers. Stereotactic X-ray imaging was then
performed and correction was made if the initial setup error exceeded
predetermined institutional tolerances, 1.5 mm for translation and 2 degrees for
rotation. Three additional sets of verification X-rays were obtained pre-, mid-,
and post-treatment for all treatments. Results: Intrafraction motion regardless
of immobilization technique was found to be 1.28 +/- 0.57 mm. The mean and
standard deviation of the variances along each direction were as follows:
Superior-inferior, 0.56 +/- 0.39 mm and 0.77 +/- 0.52 mm, (p = 0.25); Anterior
posterior, 0.57 +/- 0.43 mm and 1.14 +/- 0.61 mm, (p = 0.01); Left-right, 0.48 +/
0.34 mm and 0.74 +/- 0.40 mm, (p = 0.09) respectively. There was a significantly
greater difference in the average 3D variance of the BodyFIX as compared to the
head and shoulder mask immobilization system, 1.04 +/- 0.46 mm and 1.71 +/- 0.52
mm; (p = 0.003) respectively. Conclusions: Overall, our institution's image
guidance system using stereotactic X-ray imaging verification provides acceptable
localization accuracy as previously defined in the literature. We observed a
greater intrafraction motion for the head and shoulder mask as compared with the
BodyFIX immobilization system, which may be a result of greater C-spine mobility
and/or the suboptimal mask immobilization. Thus, better immobilization techniques
for C-spine SBRT are needed to reduce setup error and intrafraction motion. We
are currently exploring alternative C-spine immobilization techniques to improve
set up accuracy and decrease intrafraction motion during treatment.
PMID- 29333354
TI - Novel Wavelet-Based Segmentation of Prostate CBCT Images with Implanted Calypso
Transponders.
AB - Segmentation of prostate Cone Beam CT (CBCT) images is an essential step towards
real-time adaptive radiotherapy (ART). It is challenging for Calypso patients, as
more artifacts generated by the beacon transponders are present on the images. We
herein propose a novel wavelet-based segmentation algorithm for rectum, bladder,
and prostate of CBCT images with implanted Calypso transponders. For a given
CBCT, a Moving Window-Based Double Haar (MWDH) transformation is applied first to
obtain the wavelet coefficients. Based on a user defined point in the object of
interest, a cluster algorithm based adaptive thresholding is applied to the low
frequency components of the wavelet coefficients, and a Lee filter theory based
adaptive thresholding is applied on the high frequency components. For the next
step, the wavelet reconstruction is applied to the thresholded wavelet
coefficients. A binary (segmented) image of the object of interest is therefore
obtained. 5 hypofractionated Calypso prostate patients with daily CBCT were
studied. DICE, Sensitivity, Inclusiveness and DeltaV were used to evaluate the
segmentation result.
PMID- 29333355
TI - Bilateral Peripheral Nerve Field Stimulation for Intractable Coccygeal Pain: A
Case Study Using Dual Lead Intercommunication.
AB - Coccygeal pain is a difficult chronic pain problem with mixed response to various
treatments. This is a report of a case of coccygeal pain that after failing
various conservative and interventional procedures over five years was evaluated
with a temporary peripheral sacral fascial lead followed by implantation of
bilateral sacral paramedian leads for peripheral nerve field stimulation (PNFS).
This resulted in marked pain control and resumption of full activity. The visual
analog scale (VAS) pain score improved from eight pre-implant to one after
implant and has remained at that level in follow-up. Peripheral nerve field
stimulation has been reported for axial chronic back pain, post-laminectomy pain
and sacroiliac joint pain either alone or in conjunction with epidural spinal
cord stimulation. Both single and parallel leads have been used to provide wider
stimulation but differences in location have not been examined. This is the first
case report of the use of PNFS for treatment of intractable chronic coccygeal
pain. The effectiveness of PNFS was established for this patient by using a
prolonged 10-day temporary trial period followed by a 30-day interval without
stimulation during which the pain returned to the pre-trial level before
proceeding with permanent implantation, it was clear that in this case, PNFS was
effective for pain control. Interestingly, the trial and permanent leads were
both in the posterior sacral fascia but not in identical positions yet equally
effective for pain control. The observation of the effectiveness of different
positions may indicate that at least for peripheral field stimulation there may
be significant current spread in the fascia. Two and three months after the
implant, we examined the effect of different lead settings and the effect of
unilateral stimulation compared with bilateral stimulation with and without
interlead communication. The patient feedback in this case provides some
understanding of the effect of field stimulation with different lead placements.
A trial of a deep peripheral fascial lead for sacral and coccygeal field
stimulation is a simple option and may be a reasonable approach to consider in
the range of treatments for chronic coccygeal pain.
PMID- 29333356
TI - Metachronous Testicular Cancer After Orchiectomy: A Rare Case.
AB - Testicular cancer represents approximately 1% of all cancers diagnosed in males.
The prevalence of bilateral testicular germ cell tumor cases varies from 1% to
5%. Intratubular germ cell neoplasia (ITGCN) is a precursor for almost all
testicular germ cell tumors (TGCT) and is one of the highest risks of developing
contralateral testicular cancer. The radical orchiectomy is still preferred for
the treatment of testicular cancer. However, in some cases like solitary testis,
bilateral cancer or if the tumor size is under 30% percent of the testicular
extent, organ-sparing surgery can be an option. There are just a few published
reports of metachronous contralateral testicular cancer, developed after
orchiectomy with the histopathology of the intratubular germ cell neoplasia.
PMID- 29333357
TI - Salvage Stereotactic Radiosurgery for Multiple Brain Recurrences: How Much is
Enough?
AB - Stereotactic radiosurgery (SRS) can be used as a salvage treatment in selected
patients with recurrent brain metastases after previous brain radiation. We
report the case of a patient with metastatic lung adenocarcinoma who experienced
recurrence numerous times in the brain and was successfully treated each time
with SRS. For this patient, brain imaging surveillance helped identify metastases
early for salvage SRS. We have also included a discussion of published literature
regarding the neurocognitive toxicity of repeated courses of SRS.
PMID- 29333358
TI - Investigating the Seasonal and Diurnal Cycles of Ocean Vector Winds Near the
Philippines Using RapidScat and CCMP.
AB - The seasonal and diurnal cycles of ocean vector winds in the domain of the South
China Sea are characterized and compared using RapidScat and the Cross-Calibrated
Multi-Platform (CCMP) data sets. Broad agreement in seasonal flow patterns exists
between these data sets during the year 2015. Both observe the dramatic reversal
from wintertime trade winds (November-April) to westerly flow associated with the
summer monsoon (May-October). These seasonal changes have strong but not
equivalent effects on mean wind divergence patterns in both data sets.
Specifically near the Philippines, the data sets agree on several aspects of the
seasonal mean and diurnal cycle of near-surface vector winds and divergence. In
particular, RapidScat and CCMP agree that daytime onshore and nocturnal offshore
flow patterns affect the diurnal cycle of winds up to ~200 km west of Luzon,
Philippines. Observed disagreements over the diurnal cycle are explainable by
measurement uncertainty, as well as shortcomings in both data sets.
PMID- 29333359
TI - Activities of daily living independence level for home discharge in stroke
patients based on number of caregivers: an analysis of the Japan Rehabilitation
Database.
AB - Purpose This study aimed to calculate cut-off values of activities of daily
living independence level for stroke patient home discharge based on the number
of family caregivers. Method The subjects comprised 1442 stroke patients (26
hospitals) who were registered of the Japanese Rehabilitation Database. Receiver
operating characteristic curves were used to elucidate the BI and FIMR instrument
scores necessary for home discharge. Analysis was performed for each subject
according to the number of family caregivers, i.e., no caregiver, one person, two
persons or more, and overall. Result The BI cut-off points that discriminated
between home discharge and other were 65/60 points overall, 75/70 points in
patients with no caregiver, 65/60 points in patients with one caregiver, and
60/55 points in patients with two or more caregivers. The FIMR instrument cut-off
points were 90/89 points overall, 101/100 points in patients with no caregiver,
87/86 points in patients with one caregiver, and 87/86 points in patients with
two or more caregivers. Conclusion Our results indicated that home discharge for
patients with many caregivers was possible even with low ADL independence levels,
and that there was a large difference in cut-off values depending on the presence
or absence of one caregiver.
PMID- 29333360
TI - Correlation between changes of contralesional cortical activity and motor
function recovery in patients with hemiparetic stroke.
AB - OBJECTIVE: To investigate the correlation between changes of contralesional
cortical excitability evaluated by transcranial magnetic stimulation (TMS) and
functional recovery in patients with hemiparetic stroke. METHODS: Eight
inpatients (mean age: 75.9+/-13.8 years) with mild to moderate hemiparesis were
enrolled. TMS was delivered to the optimal scalp position over the contralesional
(ipsilateral to the paresis) primary motor cortex (M1) to activate the unaffected
flexor carpi radialis muscle (FCR) while the patient picked up a wooden block
with the affected hand. The amplitude of the motor-evoked potential (MEP) was
measured and then was divided by the resting MEP amplitude (MEP ratio). For
evaluation of motor function, we tested grip strength (GS), performed the upper
extremity motor section of the Fugl-Meyer Assessment (FMA-UE), and performed the
Purdue Pegboard Test (PPT) when the patients were admitted to our hospital (T1)
and 2 months after admission (T2). RESULTS: The MEP ratio was significantly
decreased at the second examination. The partial correlations between the MEP
ratio and FMA-UE at T1, and PPT of an affected hand at T2 were observed while
controlling for the period after stroke onset as the confounding variable.
CONCLUSION: The reduction of contralesional cortical hyperactivity is related to
the functional recovery in part, but not related with the period after stroke
onset. This suggests that enhanced reduction of contralesional M1 hyperactivity
contributes to functional recovery after stroke.
PMID- 29333361
TI - Factors affecting health-related quality of life one year after lumbar spinal
fusion.
AB - OBJECTIVE: To identify preoperative factors that affect the medical outcome study
36-item short form health survey (SF-36) score 1 year after lumbar spinal fusion.
METHODS: Participants were selected from among 624 patients who underwent lumbar
spinal fusion between April 1, 2009 and March 31, 2011 who were followed up for 1
year or more. The SF-36 version 2 was used to evaluate HRQOL. The following
preoperative parameters were investigated: sex, age, body mass index (BMI),
employment status (other than home-making), living with other family members,
smoking, orthopedic disorder in another part of the body (other than lumbar
spinal disease), history of lumbar spinal surgery, bladder function, and leg
muscle strength. RESULTS: 94 patients were included. None of the independent
preoperative factors exhibited a high degree of correlation, and the absence of
multicollinearity was confirmed before further analysis was performed. The first
canonical variates were age and leg muscle strength, which had a major effect on
physical functioning, role physical, and role emotional 1 year after surgery, and
the second canonical variates were employment status, sex, and orthopedic
disorder in another part of the body, which had a major effect on general health
1 year after surgery. CONCLUSIONS: The SF-36 score 1 year after lumbar spinal
fusion was affected by the preoperative factors of age, leg muscle strength,
living with other family members, employment status, sex, and orthopedic
disorders in another part of the body.
PMID- 29333362
TI - The coordination of joint movements during sit-to-stand motion in old adults: the
uncontrolled manifold analysis.
AB - OBJECTIVE: Sit-to-stand motion (STS) is a dynamic motion utilized in fundamental
activities of daily living and requires extensive joint movement in the lower
extremities and the trunk and coordination of multiple body segments. The present
study aimed to investigate whether aging affects the motor coordination of joint
movements required to stabilize the horizontal and vertical movement of center of
mass using the uncontrolled manifold (UCM) analysis. METHOD: We recruited 39
older adults with no musculoskeletal and/or neuromuscular conditions that
affected STS, along with 21 healthy younger adults. All subjects performed five
STS trials from a chair with the seat height adjusted to the length of their
lower leg at a self-selected motion speed. Kinematic data were collected using a
three-dimensional motion analysis system. We performed the UCM analysis to assess
the effects of joint angle variance (elemental variable) to stabilize the
horizontal and vertical movement of COM (performance variable) and calculated the
joint angle variance that does not affect COM (VUCM), the variance that affects
COM (VORT), and the synergy index (DeltaV). RESULTS: DeltaV values in the
horizontal direction were higher in the older adults than in the younger adults,
but DeltaV values in the vertical direction were lower in the older adults than
in the younger adults. CONCLUSION: Older adults require increasing levels of
stabilization of horizontal movement of COM after buttocks-off in the STS
maneuver. As a result, variance in the joint angle of the lower extremities
indicated no kinematic synergy for stabilizing the vertical movement of COM.
PMID- 29333364
TI - Biodegradable osteofixation in bimaxillary orthognathic surgery.
PMID- 29333363
TI - Creating a multi-center rare disease consortium - the Consortium of Eosinophilic
Gastrointestinal Disease Researchers (CEGIR).
AB - Eosinophilic gastrointestinal disorders (EGIDs) affect various segments of the
gastrointestinal tract. Since these disorders are rare, collaboration is
essential to enroll subjects in clinical studies and study the broader
population. The Rare Diseases Clinical Research Network (RDCRN), a program of the
National Center for Advancing Translational Sciences (NCATS), funded the
Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) in 2014
to advance the field of EGIDs. CEGIR facilitates collaboration among various
centers, subspecialties, patients, professional organizations and patient
advocacy groups and includes 14 clinical sites. It has successfully initiated two
large multi-center clinical studies looking to refine EGID diagnoses and
management. Several pilot studies are underway that focus on various aspects of
EGIDs including novel therapeutic interventions, diagnostic and monitoring
methods, and the role of the microbiome in pathogenesis. CEGIR currently nurtures
five physician-scholars through a career training development program and has
published more than 40 manuscripts since its inception. This review focuses on
CEGIR's operating model and progress and how it facilitates a framework for
exchange of ideas and stimulates research and innovation. This consortium
provides a model for progress on other potential clinical areas.
PMID- 29333365
TI - Association between headache and temporomandibular disorder.
AB - Headaches are one of the most common conditions associated with temporomandibular
disorder (TMD). In the present paper, we evaluated the relationship between
headache and TMD, determined whether headache influences the symptoms of TMD, and
reported two cases of TMD accompanied by headache. Our practical experience and a
review of the literature suggested that headache increases the frequency and
intensity of pain parameters, thus complicating dysfunctional diseases in both
diagnostic and treatment phases. Therefore, early and multidisciplinary treatment
of TMD is necessary to avoid the overlap of painful events that could result in
pain chronicity.
PMID- 29333366
TI - A review of temporomandibular joint-related papers published between 2014-2015.
AB - We conducted a retrospective study and reviewed the temporomandibular joint (TMJ)
related papers published in a leading international journal, Journal of Oral and
Maxillofacial Surgery, between January 2014 and December 2015. The study was
conducted to ascertain and compare the trends of articles being published in the
years 2014 and 2015. A total of 28 articles were reviewed, of which most of the
full-length articles were on clinical management and outcomes and the role of
radiology. The bulk of the studies were prospective, and less interest was shown
in experimental research. A thorough review and analysis thus gives the
impression that there is a great need for well-designed clinical studies on TMJ.
PMID- 29333367
TI - Stepwise verification of bone regeneration using recombinant human bone
morphogenetic protein-2 in rat fibula model.
AB - Objectives: The purpose of this study was to introduce our three experiments on
bone morphogenetic protein (BMP) and its carriers performed using the critical
sized segmental defect (CSD) model in rat fibula and to investigate development
of animal models and carriers for more effective bone regeneration. Materials and
Methods: For the experiments, 14, 16, and 24 rats with CSDs on both fibulae were
used in Experiments 1, 2, and 3, respectively. BMP-2 with absorbable collagen
sponge (ACS) (Experiments 1 and 2), autoclaved autogenous bone (AAB) and fibrin
glue (FG) (Experiment 3), and xenogenic bone (Experiment 2) were used in the
experimental groups. Radiographic and histomorphological evaluations were
performed during the follow-up period of each experiment. Results: Significant
new bone formation was commonly observed in all experimental groups using BMP-2
compared to control and xenograft (porcine bone) groups. Although there was some
difference based on BMP carrier, regenerated bone volume was typically reduced by
remodeling after initially forming excessive bone. Conclusion: BMP-2 demonstrates
excellent ability for bone regeneration because of its osteoinductivity, but
efficacy can be significantly different depending on its delivery system. ACS and
FG showed relatively good bone regeneration capacity, satisfying the essential
conditions of localization and release-control when used as BMP carriers. AAB
could not provide release-control as a BMP carrier, but its space-maintenance
role was remarkable. Carriers and scaffolds that can provide sufficient support
to the BMP/carrier complex are necessary for large bone defects, and AAB is
thought to be able to act as an effective scaffold. The CSD model of rat fibula
is simple and useful for initial estimate of bone regeneration by agents
including BMPs.
PMID- 29333368
TI - Oral lesions associated with human immunodeficiency virus in 75 adult patients: a
clinical study.
AB - Objectives: The objective of this study was to investigate the presence of oral
lesions in human immunodeficiency virus/acquired immunodeficiency syndrome
(HIV/AIDS) patients in a descriptive cross-sectional study, and to establish
their presence according to levels of CD4+ cells (including the CD4+/CD8+ cell
ratio). Materials and Methods: A total of 75 patients infected with HIV were
included. Oral lesions were observed and classified using World Health
Organization classification guidelines. Potential correlations between the
presence and severity of oral lesions and CD4+ cells, including the CD4+/CD8+
cell ratio, were studied. Results: The most frequent oral lesion detected was
oral pseudomembranous candidiasis (80.0%), followed by periodontal disease
(40.0%), herpetic lesions (16.0%), hairy leukoplakia (16.0%), gingivitis (20.0%),
oral ulceration (12.0%), Kaposi's sarcoma (8.0%), and non-Hodgkin's lymphoma
(4.0%). The CD4+ count was <200 cells/mm3 in 45 cases (60.0%), between 200-500
cells/mm3 in 18 cases (24.0%), and >500 cells/mm3 in 12 cases (16.0%). The mean
CD4+ count was 182.18 cells/mm3. The mean ratio of CD4+/CD8+ cells was 0.26. All
patients showed at least one oral manifestation. Conclusion: There was no
correlation between the CD4+/CD8+ cell ratio and the presence of oral lesions.
The severity of the lesions was more pronounced when the CD4+ cell count was less
than 200 cells/mm3.
PMID- 29333369
TI - Assessment of the anterior loop of the inferior alveolar nerve via cone-beam
computed tomography.
AB - Objectives: The aim of this study was to evaluate different anatomical variants
of the anterior loop of the inferior alveolar nerve (IAN) via cone-beam computed
tomography (CBCT). Materials and Methods: CBCT images of 71 patients (36 males
and 35 females) were evaluated. We used the classification described by Solar for
IAN evaluation. In this classification, three different types of IAN loops were
introduced prior to emerging from the mental foramen. We classified patients
according to this system and introduced a new, fourth type. Results: Type I was
seen in 15 sites (10.6%), type II in 39 sites (27.5%), and type III in 50 sites
(35.2%). We found a new type in 38 sites (26.8%) that constituted a fourth type.
Conclusion: We found that type III was the most common variant. In the fourth
type, the IAN was not detectable because the main nerve was adjacent to the
cortical plate and the incisive branch was thinner than the main branch and
alongside it. In this type, more care is needed for surgeries including inferior
alveolar and mental nerve transposition.
PMID- 29333370
TI - The efficacy of oral habit modification on headache.
AB - Objectives: Headache is the most common complaint of patients suffering from
temporomandibular joint disorders (TMDs). Thus, temporomandibular joint (TMJ)
examinations maybe necessary in patients with headache. Considering the high
prevalence of bruxism and TMDs in patients with headache the effects of
conservative TMD treatment on headache should be assessed. Materials and Methods:
Patients were questioned about headaches in the past three months. Those
responding affirmatively to this question were examined for TMD and bruxism.
After the examinations, 219 patients remained in the study and received self
management instructions. Patients were requested to modify oral habits except
when eating or sleeping. The degree of pain (visual analogue scale), headache
disability index (HDI), frequency of headaches (FH) per month and TMD intensity
were evaluated. Results: The median levels of pain, HDI, FH, and TMD intensity
were 8, 44, 8, and 7, respectively, before modifying oral habits and decreased to
4, 24, 2, and 3, respectively, after intervention. These decreases were
statistically significant. Conclusion: Having patients maintain free space
between the teeth and relax muscles can be an efficient method to treat headache
and TMD, especially when repeated frequently.
PMID- 29333371
TI - Use of repeat anterior maxillary distraction to correct residual midface
hypoplasia in cleft patients.
AB - Objectives: The study was designed to evaluate the efficacy of performing a
second, repeat anterior maxillary distraction (AMD) to treat residual cleft
maxillary hypoplasia. Materials and Methods: Five patients between the ages of 12
to 15 years with a history of AMD and with residual cleft maxillary hypoplasia
were included in the study. Inclusion was irrespective of gender, type of cleft
lip and palate, and the amount of advancement needed. Repeat AMD was executed in
these patients 4 to 5 years after the primary AMD procedure to correct the cleft
maxillary hypoplasia that had developed since the initial procedure.
Orthopantomogram (OPG) and lateral cephalograms were taken for evaluation
preoperatively, immediately after distraction, after consolidation, and one year
postoperatively. The data obtained was tabulated and a Mann Whitney U-test was
used for statistical comparisons. Results: At the time of presentation, a
residual maxillary hypoplasia was observed with a well maintained distraction gap
on the OPG which ruled out the occurrence of a relapse. Favorable movement of the
segments without any resistance was seen in all patients. Mean maxillary
advancement of 10.56 mm was achieved at repeat AMD. Statistically significant
increases in midfacial length, SNA angle, and nasion perpendicular to point A
distance was achieved (P=0.012, P=0.011, and P=0.012, respectively). Good profile
was achieved for all patients. Minimal transient complications, for example
anterior open bite and bleeding episodes, were managed. Conclusion: Addressing
the problem of cleft maxillary hypoplasia at an early age (12-15 years) is
beneficial for the child. Residual hypoplasia may develop in some patients, which
may require additional corrective procedures. The results of our study show that
AMD can be repeated when residual deformity develops with the previous procedure
having no negative impact on the results of the repeat procedure.
PMID- 29333372
TI - Ghost cell odontogenic carcinoma on right mandible and its respective surgical
reconstruction: a case report.
AB - Calcifying cystic odontogenic tumor (CCOT) is defined as an odontogenic cyst-like
benign neoplasm that characteristically contains several ghost cells,
ameloblastoma-like epithelium, and occasional calcification. Ghost cell
odontogenic carcinoma (GCOC), a malignant form of CCOT, is an exceptionally rare
malignant tumor. In this report, we present a case of a 53-year-old man whose
chief complaint was a solitary mass on the right mandible area. The mass was
completely removed through an extraoral surgical approach and reconstructive
surgery was performed in two phases.
PMID- 29333373
TI - Correction of congenital cleft earlobe with front and back flaps.
AB - Congenital auricular deformities may be either deformational or malformational.
Malformational anomalies present with a skin or cartilage shortage. Two cases
with congenital cleft earlobe were presented. A new surgical technique using a
two-layered repair with front and back flaps were introduced. She waited to begin
wearing earrings until six months after the surgery to prevent possible scar
contracture. The patients were followed up for a period ranging from 3 to 14
months. The earlobe volume deficiency was replaced, and acceptable scar
maturation was obtained.
PMID- 29333374
TI - Asymptomatic bilateral maxillary and mandibular impacted permanent canines:
serendipity in dental outpatient department.
PMID- 29333375
TI - Impact of FTO SNPs rs9930506 and rs9939609 in Prostate Cancer Severity in a
Cohort of Puerto Rican Men.
AB - Background: Obesity is prevalent in PR and has been associated with prostate
cancer (PCa) mortality and aggressiveness. Polymorphisms (SNPs) rs9930506 and
rs9939609 in the FTO gene have been associated with both obesity and PCa. The aim
of this work was to ascertain whether the presence of these SNPs is associated
with PCa risk and severity in a cohort of Puerto Rican men. Methods and findings:
The study population consisted of 513 Puerto Rican men age ranging from 40-79
years old who underwent radical prostatectomy (RP) as the first treatment for PCa
and 128 healthy Puerto Rican men age ranging from 40-79 years old. Genomic DNA
(gDNA) was extracted and SNPs were determined by Real-Time PCR. PCa severity was
defined based on RP stage and Gleason Score. The relationship of FTO SNPs with
demographic, clinical characteristics, PCa status and PCa severity were assessed.
Logistic regression models with a 95% confidence interval (CI) determined SNPs
interaction with PCa risk and severity odds ratio (ORs). Results and discussion:
BMI, age and PSA were considered as confounders. Hardy-Weinberg equilibrium was
present for both SNPs. The heterozygous forms (A/G; T/A) were the most prevalent
genotypes and the frequency of alleles and genotypes for both SNPs agreed with
those published in 1000 genomes. Results suggest an inverse association between
the mutated rs9939609 and the risk of having PCa (OR: 0.53, 95% CI: 0.31-0.92)
and a positive association with overweight (OR: 1.05, 95% CI: 0.68-1.62).
Importantly, among the cases that were overweight, those with mutated rs9939609
had a greater chance of high severity PCa (OR: 1.39, 95% CI: 0.84-2.32) although
these results were not statistical significant upon adjustment. Limitations of
the study were the relatively small cohort and lack of access to the weight
history of all our subjects. Conclusion: Results offer a research line to be
followed with an expanded number of subjects that may provide a better
statistical significance, to unravel the high mortality rate in this population.
PMID- 29333377
TI - Dietary L-Arginine Intakes and the Risk of Metabolic Syndrome: A 6-Year Follow-Up
in Tehran Lipid and Glucose Study.
AB - This study was conducted to investigate whether regular dietary intake of L
arginine could affect the occurrence of metabolic syndrome (MetS). Eligible adult
men and women (n=1,237), who participated in the Tehran Lipid and Glucose Study,
were followed for a median of 6.3 years. Dietary intakes of L-arginine and serum
nitrate and nitrite (NOx) concentration were assessed at baseline (2006~2008),
and demographics, anthropometrics, and biochemical variables were evaluated at
baseline and follow-up examinations. The occurrence of MetS was assessed in
relation to total L-arginine, intakes of L-arginine from animal and plant
sources, with adjustment of potential confounding variables. Participants who had
higher intake of L-arginine also had higher serum NOx at baseline (35.0 vs. 30.5
MUmol/L, P<0.05). After 6 years of follow-up, higher intakes of L-arginine from
animal sources were accompanied with increased risk of MetS [odd ratios
(OR)=1.49, 95% confidence interval (95% CI)=1.02~2.18]. Compared to the lowest,
the highest intakes of L-arginine from plant sources were related to
significantly reduced risk of MetS (OR=0.58, 95% CI=0.32~0.99). In conclusion,
our findings suggest a potentially protective effect of plant derived L-arginine
intakes against development of MetS and its phenotypes; moreover, higher intakes
of L-arginine from animal sources could be a dietary risk factor for development
of metabolic disorders.
PMID- 29333378
TI - Associations between Self-Reported Sleep Quality and Duration and Dietary
Consumptions, Psychological Symptoms, and Obesity in Korean Adults.
AB - Sleep pattern disruptions have been reported to be associated with an increased
risk of obesity. This study was performed to investigate the association between
sleep quality and sleep duration with dietary consumption, psychological factors,
and obesity in Korean adults. A total of 288 Korean men and women who visited a
public health center were included in this study. Data on general
characteristics, health-related habits, psychological symptoms, dietary intake,
and sleep patterns (including quality and duration) were collected using self
report questionnaires. Approximately half of the included Korean adults
experienced sleep of low quality and short duration. Subjects who reported short
sleep durations had a significantly higher weight (P=0.015), body mass index
(P<0.001), and prevalence of obesity (P=0.012) than those reporting proper sleep
durations. After adjustment for covariates, subjects reporting short sleep
durations consumed more dietary carbohydrates (P=0.043) and higher levels of
perceived stress (P=0.001), depression (P=0.001), and anxiety (P<0.001) than
subjects reporting proper sleep durations. However, obesity-related variables,
dietary intake and psychosocial symptoms did not differ significantly by reported
sleep quality. The results of this study demonstrated that sleep duration but not
sleep quality was associated with dietary macronutrient intake and psychological
symptoms, which might affect obesity.
PMID- 29333376
TI - Anti-Inflammatory and Anti-Obesity Properties of Food Bioactive Components:
Effects on Adipose Tissue.
AB - Obesity is an epidemic and costly disease affecting 13% of the adult population
worldwide. Obesity is associated with adipose tissue hypertrophy and hyperplasia,
as well as pathologic endocrine alterations of adipose tissue including local and
chronic systemic low-grade inflammation. Moreover, this inflammation is a risk
factor for both metabolic syndrome (MetS) and insulin resistance. Basic and
clinical studies demonstrate that foods containing bioactive compounds are
capable of preventing both obesity and adipose tissue inflammation, improving
obesity-associated MetS in human subjects and animal models of obesity. In this
review, we discuss the anti-obesity and anti-inflammatory protective effects of
some bioactive polyphenols of plant origin and omega-3 polyunsaturated fatty
acids, available for the customers worldwide from commonly used foods and/or as
components of commercial food supplements. We review how these bioactive
compounds modulate cell signaling including through the nuclear factor-kappaB,
adenosine monophosphate-activated protein kinase, mitogen-activated protein
kinase, toll-like receptors, and G-protein coupled receptor 120 intracellular
signaling pathways and improve the balance of pro- and anti-inflammatory
mediators secreted by adipose tissue and subsequently lower systemic inflammation
and risk for metabolic diseases.
PMID- 29333379
TI - Broccoli (Brassica oleracea) Reduces Oxidative Damage to Pancreatic Tissue and
Combats Hyperglycaemia in Diabetic Rats.
AB - Oxidative stress plays a pivotal role in the development of diabetes and
hyperglycaemia. The protective effects of natural extracts against diabetes are
mainly dependent on their antioxidant and hypoglycaemic properties. Broccoli
(Brassica oleracea) exerts beneficial health effects in several diseases
including diabetes; however, the mechanism has not been elucidated yet. The
present study was carried out to evaluate the potential hypoglycaemic and
antioxidant properties of aqueous broccoli extracts (BEs) in diabetic rats.
Streptozotocin (STZ) drug was used as a diabetogenic agent in a single
intraperitoneal injection dose of 50 mg/kg body weight. The blood glucose level
for each rat was measured twice a week. After 8 weeks, all animals were fasted
overnight and sacrificed; pancreatic tissues were homogenized and used for
measuring oxidative DNA damage, biochemical assessment of glutathione (GSH), and
total antioxidant capacity (TAC) as well as histopathological examination for
pancreatic tissues was examined. Diabetic rats showed significantly higher levels
of DNA damage, GSH depletion, and impaired TAC levels in comparison to non
diabetics (P<0.05). The treatment of diabetic rats with BE significantly reduced
DNA damage and conserved GSH and TAC values (P<0.01). BE attenuated pancreatic
histopathological changes in diabetic rats. The results of this study indicated
that BE reduced the STZ mediated hyperglycaemia and the STZ-induced oxidative
injury to pancreas tissue. The used in vivo model confirmed the efficacy of BE as
an anti-diabetic herbal medicine and provided insights into the capacity of BE to
be used for phytoremediation purposes for human type 2 diabetes.
PMID- 29333380
TI - Anti-Obesity Property of Lichen Thamnolia vermicularis Extract in 3T3-L1 Cells
and Diet-Induced Obese Mice.
AB - Thamnolia vermicularis (TV) is an edible lichen that is prevalent in the alpine
zone of East Asia. This study evaluated the feasibility of using TV acetone
extracts as a functional food based on experiments using cell line and obese
mice. The cellular triglyceride levels and Oil red O staining of 3T3-L1 cells
indicated that TV extracts (5 and 10 MUg/mL) dose-dependently suppressed
adipocyte differentiation and lipid accumulation compared with the control. The
TV extract (0.4%, w/w) in a high-fat diet (HFD) was supplemented to C57BL/6N mice
for 12 weeks, and TV extract supplement significantly reduced visceral fat mass
and body weight compared with HFD feeding alone. The TV extract also induced
significant decreases in serum and hepatic lipids, whereas it increased the serum
high-density lipoproteins-cholesterol/total cholesterol ratio and fecal lipids
levels. Moreover, the TV extract led to significantly lower homeostasis model
assessment of insulin resistance in diet-induced obese mice. Taken together,
these results suggest that the TV extract may have anti-obesity effects,
including lipid-lowering, and it is a natural resource with the potential for use
in obesity management.
PMID- 29333381
TI - Changes in Drosophila melanogaster Sleep-Wake Behavior Due to Lotus (Nelumbo
nucifera) Seed and Hwang Jeong (Polygonatum sibiricum) Extracts.
AB - We evaluated the sleep enhancement activity of the medicinal herbs valerian
(Valeriana officinalis), jujube (Ziziphus jujube), lotus seed (Nelumbo nucifera),
Gastrodia elata, Polygonatum sibiricum, and baekbokryung (Poria cocos), which can
relieve insomnia in a Drosophila model. Locomotor activity was measured in the
Drosophila model to evaluate the sleep activity of Korean medicinal herbs
traditionally used as sleep aids. The group treated with lotus seed extract
showed less nocturnal activity. Treatment with 10 or 20 mg/mL of P. sibiricum
significantly reduced nocturnal activity compared to the control group (P<0.05).
The activity and sleep bouts of fruit flies were significantly decreased by a
high-dose treatment (10 mg/mL) of lotus or P. sibiricum extracts at night.
Caffeine-treated Drosophila showed increased nocturnal activity and decreased
total sleep time (P<0.05). Flies receiving the 10 mg-doses of lotus seed or P.
sibiricum extract showed significantly different nocturnal locomotor activity and
total sleep time compared to caffeine-treated Drosophila. Lotus seed and P.
sibiricum extracts are attractive and valuable sleep-potentiating nutraceuticals.
PMID- 29333382
TI - Antioxidant and Quinone Reductase Activity of Soyasaponins in Hepa1c1c7 Mouse
Hepatocarcinoma Cells.
AB - Saponins have been reported to possess several health beneficial activities
including hypocholesterolemic, immune-stimulatory, and anticarcinogenic. The
objectives of this study were to determine if soysaponins are radical scavengers
and inducers of quinone reductase (QR) activity in Hepa1c1c7 murine hepatoma cell
line. The antioxidant capacity of soyasaponin was evaluated using the 1,1'
diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6
sulfonic acid) (ABTS) radical scavenging methods. Soyasaponin showed 75.7%
radical scavenging activity in the DPPH assay and 81.4% in the ABTS method at 100
MUg/mL concentration. Cellular proliferation was determined using the
methylthiazolyldiphenyl-tetrazolium bromide colorimetric assay. Soyasaponin
inhibited cell growth in a dose-dependent (0.1~100 MUg/mL) manner, and growth
inhibition was 30% and 39% at 100 MUg/mL of saponin after 24 h and 48 h
incubation, respectively. Soyasaponin showed QR induction in a dose-dependent
manner. Ten, 50, and 100 MUg/mL of soyasaponin resulted in a 1.6-, 2.2-, and 2.9
fold induction of QR, respectively. These results provide a basis for the
potential of soysaponin as a chemopreventive agent.
PMID- 29333383
TI - Inhibitory Effects of Butein on Adipogenesis through Upregulation of the Nrf2/HO
1 Pathway in 3T3-L1 Adipocytes.
AB - Butein is reported to have many biological effects, including anti-fibrogenic,
anti-cancer, and anti-inflammatory activities. This study investigated the
effects of butein on adipocyte differentiation and the Nrf2/heme oxygenase-1 (HO
1) pathway's involvement in its anti adipogenic mechanism. Butein treatment
reduced protein expression of key adipogenic transcription factors such as CCAAT
enhancer-binding protein alpha (C/EBPalpha) and peroxisome proliferator-activated
receptor gamma (PPARgamma). At a concentration of 5, 10, and 25 MUM butein,
PPARgamma was decreased by 78.8, 68.3, and 31.4% and C/EBPalpha by 87.3, 71.7,
and 42.1%, respectively. Butein also increased Nrf2 and HO-1 protein expression
in a dose-dependent manner. Treatment with zinc protoporphyrin, a specific HO-1
inhibitor, abolished the inhibitory effects of butein on adipogenic transcription
factor protein expression. Therefore, butein inhibits adipogenesis, at least
partially, through upregulation of the Nrf-2/HO-1 signaling pathway in 3T3-L1
adipocytes.
PMID- 29333384
TI - Antioxidant and Cytoprotective Activities of Enzymatic Extracts from Rhizoid of
Laminaria japonica.
AB - Rhizoid of Laminaria japonica was hydrolyzed with proteases and carbohydrases to
obtain antioxidant materials. Oxygen radical absorbance capacity (ORAC) of the
enzymatic extracts was evaluated and the Protamex extract (PE) exhibited the
highest ORAC value. PE also potently scavenged 2,2-diphenyl-1-picrylhydrazyl
radical, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic) acid cation radical,
and hydrogen peroxide (H2O2) and had good reducing power. PE inhibited hydroxyl
radical-induced DNA scission by measuring the conversion of supercoiled pBR322
plasmid DNA to the open circular form. The cytoprotective effect of PE against
H2O2-induced hepatic cell damage was also investigated. PE showed a dose
dependent cytoprotective effect in cultured hepatocytes by inhibiting
intracellular reactive oxygen species scavenging activity. In addition, PE up
regulated the expression of heme oxygenase-1, which is a cytoprotective enzyme,
by activating translocation of nuclear factor-erythroid 2-related factor 2. Taken
together, the enzymatic extract of rhizoid of L. japonica, particularly PE, may
be useful for antioxidant additives.
PMID- 29333385
TI - Kaempferol Inhibits Angiogenesis by Suppressing HIF-1alpha and VEGFR2 Activation
via ERK/p38 MAPK and PI3K/Akt/mTOR Signaling Pathways in Endothelial Cells.
AB - Kaempferol has been shown to inhibit vascular formation in endothelial cells.
However, the underlying mechanisms are not fully understood. In the present
study, we evaluated whether kaempferol exerts antiangiogenic effects by targeting
extracellular signal-regulated kinase (ERK)/p38 mitogen-activated protein kinase
(MAPK) and phosphoinositide 3-kinase (PI3K)/Akt/mechanistic target of rapamycin
(mTOR) signaling pathways in endothelial cells. Endothelial cells were treated
with various concentrations of kaempferol for 24 h. Cell viability was determined
by the 3- (4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay;
vascular formation was analyzed by tube formation, wound healing, and mouse
aortic ring assays. Activation of hypoxia-inducible factor-1alpha (HIF-1alpha),
vascular endothelial growth factor receptor 2 (VEGFR2), ERK/p38 MAPK, and
PI3K/Akt/mTOR was analyzed by Western blotting. Kaempferol significantly
inhibited cell migration and tube formation in endothelial cells, and suppressed
microvessel sprouting in the mouse aortic ring assay. Moreover, kaempferol
suppressed the activation of HIF-1alpha, VEGFR2, and other markers of ERK/p38
MAPK and PI3K/Akt/mTOR signaling pathways in endothelial cells. These results
suggest that kaempferol inhibits angiogenesis by suppressing HIF-1alpha and
VEGFR2 activation via ERK/p38 MAPK and PI3K/Akt/mTOR signaling in endothelial
cells.
PMID- 29333386
TI - Antioxidant and Anti-Adipogenic Activities of Trapa japonica Shell Extract
Cultivated in Korea.
AB - Trapa japonica shell contains phenolic compounds such as tannins. Studies
regarding the antioxidant and anti-adipogenic effects of Trapa japonica shell
cultivated in Korea are still unclear. Antioxidant and anti-adipogenic activities
were measured by in vitro assays such as 2,2-diphenyl-1-picrylhydrazy (DPPH)
radical scavenging activity, 2,2'-azinobis( 3-ethylbenzothiazoline-6-sulphonic
acid) (ABTS) radical scavenging activity, ferric reducing ability of plasma
assay, reducing power, superoxide dismutase-like activity, and iron chelating
ability in 3T3-L1 cells. We also measured the total phenol and flavonoids
contents (TPC and TFC, respectively) in Trapa japonica shell extract. Our results
show that TPC and TFC of Trapa japonica shell extract were 157.7+/-0.70 mg gallic
acid equivalents/g and 25.0+/-1.95 mg quercetin equivalents/g, respectively.
Trapa japonica shell extract showed strong antioxidant activities in a dose
dependent manner in DPPH and ABTS radical scavenging activities and other
methods. Especially, the whole antioxidant activity test of Trapa japonica shell
extract exhibited higher levels than that of butylated hydroxytoluene as a
positive control. Furthermore, Trapa japonica shell extract inhibited lipid
accumulation and reactive oxygen species production during the differentiation of
3T3-L1 preadipocytes. Trapa japonica shell extract possessed a significant
antioxidant and anti-adipogenic property, which suggests its potential as a
natural functional food ingredient.
PMID- 29333387
TI - Physicochemical and Antioxidant Properties of Honeys from the Sundarbans Mangrove
Forest of Bangladesh.
AB - This study evaluated the physicochemical, nutritional, antioxidant, and phenolic
properties of ten honey samples from the Sundarbans mangrove forest, Bangladesh.
The average pH, electrical conductivity, total dissolved solid, ash, moisture,
hydroxymethyl furfural, titrable acidity, and absorbance were 4.3, 0.38 mS/cm,
187.5 ppm, 0.14%, 17.88%, 4.4 mg/kg, 37.7 meq/kg, and 483 mAU, respectively. In
the honeys, the average contents of Ca, Cu, Fe, K, Mg, Mn, and Na were 95.5,
0.19, 6.4, 302, 39.9, 3.4, and 597 ppm, respectively, whereas Cd, Cr, Pb, and Ni
were not found. The average contents of total sugar, protein, lipid, vitamin C,
polyphenols, flavonoids, and anthocyanins in the honeys were 69.3%, 0.8%, 0.29%,
107.3 mg/kg, 757.2 mg gallic acid equivalent/kg, 43.1 mg chatechin equivalent/kg,
and 5.4 mg/kg, respectively. The honeys had strong 1,1-diphenyl-2-picrylhydrazyl
free radical scavenging activity, reducing power and total antioxidant capacity.
High-performance liquid chromatography analysis of the honey fractions revealed
the quantification of six polyphenols namely, (+)-catechin, (-)-epicatechin, p
caumeric acid, syringic acid, trans-cinnamic acid, and vanillic acid at 194.98,
330.34, 74.64, 218.97, 49.55, and 118.84 mg/kg, respectively. Therefore, the
honeys in the Sundarbans are of excellent quality and a prospective source of
polyphenols, and antioxidants.
PMID- 29333388
TI - Enhancement of Phenolic Production and Antioxidant Activity from Buckwheat Leaves
by Subcritical Water Extraction.
AB - To enhance the production of phenolic compounds with high antioxidant activity
and reduce the level of phototoxic fagopyrin, buckwheat leaves were extracted
with subcritical water (SW) at 100~220 degrees C for 10~50 min. The major
phenolic compounds were quercetin, gallic acid, and protocatechuic acid. The
cumulative amount of individual phenolic compounds increased with increasing
extraction temperature from 100 degrees C to 180 degrees C and did not change
significantly at 200 degrees C and 220 degrees C. The highest yield of individual
phenolic compounds was 1,632.2 MUg/g dry sample at 180 degrees C, which was 4.7
fold higher than that (348.4 MUg/g dry sample) at 100 degrees C. Total phenolic
content and total flavonoid content increased with increasing extraction
temperature and decreased with increasing extraction time, and peaked at 41.1 mg
gallic acid equivalents/g and 26.9 mg quercetin equivalents/g at 180 degrees C/10
min, respectively. 2,2-Diphenyl-1-picrylhydrazyl free radical scavenging activity
and ferric reducing ability of plasma reached 46.4 mg ascorbic acid equivalents/g
and 72.3 mmol Fe2+/100 g at 180 degrees C/10 min, respectively. The fagopyrin
contents were reduced by 92.5~95.7%. Color values L* and b* decreased, and a*
increased with increasing extraction temperature. SW extraction enhanced the
yield of phenolic compounds with high antioxidant activity and reduced the
fagopyrin content from buckwheat leaves.
PMID- 29333389
TI - Influence of Cooking Methods on Bioactive Compound Content and Antioxidant
Activity of Brussels Sprouts.
AB - The effects of different cooking methods on total bioactive compound content were
determined, and in vitro antioxidant activity in 80% ethanolic extracts of
Brussels sprouts was evaluated by spectrophotometric methods. Compared to
uncooked, steamed, and microwaved Brussels sprouts extracted with 80% ethanol
contained higher amounts of total polyphenols. Uncooked Brussels sprouts
contained the highest amounts of total flavonoids. Microwaved Brussels sprouts
contained the highest amounts of total carotenoids (0.35 mg/g) and chlorophylls
(3.01 mg/g), followed by steamed and uncooked samples. Uncooked fresh Brussels
sprouts showed the highest antioxidant activity followed by microwaved and
steamed sprouts. Antioxidant activity was measured with the 2,2-diphenyl-1
picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and
hydroxyl racial scavenging assays as well as the reducing power activity assay,
and antioxidant activity was found to increase in a concentration-dependent
manner. Based on these results, cooking or heat treatment may decrease
antioxidant activities, although their effect on bioactive compound content
remains controversial.
PMID- 29333390
TI - Physicochemical and Consumer Acceptance of Tofu Supplemented with Licorice
Powder.
AB - To develop functionally and nutritionally improved tofu, the effects of partial
(0.2~0.8%) replacement with licorice powder (LP) on the quality characteristics
of tofu were investigated. The pH and turbidity values decreased upon addition of
increasing amounts of LP (P<0.05). The yield of LP-supplemented tofu was higher
than that of the control tofu, and it increased as the concentration of LP
increased (P<0.05). Substituting 0.6% and above of LP significantly hardened the
texture of tofu (P<0.05) while control and 0.2~0.4% samples were not
significantly different among them (P> 0.05). Lightness significantly decreased
with higher LP content in the formulation (P<0.05), as indicated by visual
observation that the color of tofu became darker. Redness and yellowness
significantly increased (P<0.05). 2,2-Diphenyl-1-picrylhydrazyl and 2,2'-azino
bis-3-ethylbenzthiazoline-6-sulphonic acid radical scavenging activities
significantly increased (P<0.05) with higher substitution of LP, and they were
well correlated. Tofu incorporated with LP (0.2~0.8%) had a better shelf life
which was approximately 4.32~26.64 h longer than the control tofu at the elevated
temperature of 15 degrees C. Finally, consumer acceptance test revealed that
supplementation of LP more than 0.4% had an adverse effect on general consumer
acceptance. On the basis of the overall observations, tofu samples supplemented
with 0.2% (w/w) LP were found to benefit from the functional properties of LP,
without compromising consumer acceptance.
PMID- 29333391
TI - Analysis of Antioxidant and Anti-Inflammatory Activities of Solvent Fractions
from Rhynchosia nulubilis Cultivated with Ganoderma lucidum Mycelium.
AB - In this study, the crude ethanol Rhynchosia nulubilis cultivated with Ganoderma
lucidum mycelium (RNGM) extract was solvent fractionated with organic solvents
such as n-hexane, chloroform, ethyl acetate, and water. The anticancer
activities, anti-inflammatory activity total polyphenols, total flavonoids,
isoflavones, and beta-glucan of the solvent fractions of RNGM were studied. The
ethyl acetate fraction showed the highest 2,2-diphenyl-1-picrylhydrazyl
scavenging activity of 76.60% at 800 MUg/mL. The ethyl acetate fraction also
showed higher antioxidant activity in 2,2'-azino-bis(3-ethylbenzothiazoline-6
sulfonic acid) and ferric reducing ability of plasma assays compared to the other
fractions. In addition, this study confirmed that the ethyl acetate fraction
strongly inhibited nitric oxide production. The ethyl acetate fraction had the
highest amount of total polyphenol and total flavonoid (65.33 mg gallic acid
equivalent/g and 18.50 mg quercetin equivalent/g, respectively). The ethyl
acetate fraction (13.02%) showed the highest amount of total beta-glucan,
followed by the water (6.32%), chloroform (1.43%), and n-hexane fraction (0.85%).
Therefore, it is suggested that the ethyl acetate fraction of Rhynchosia
nulubilis cultivated with Ganoderma lucidum mycelium may be potential natural
sources for nutritional and pharmaceutical applications.
PMID- 29333392
TI - Enhancing Sensory Perception of Plant Based Nutraceutical Drinks by Combining
Plants from Different Sources: A Preliminary Study of Tea and Ginger Blend.
AB - Tea-ginger drink was selected for evaluation due to its nutraceutical potential.
Panelists rated preference for drinks prepared from tea, ginger, and tea+ginger
powder for colour, taste, and aroma. The obtained data were evaluated using
analysis of variance, principal component analysis, and agglomerative
hierarchical clustering. Also the colour preference scores were evaluated against
instrumental colour measurements. The ginger drink had lower rating for colour
preference and the tea drink had lower ratings for aroma and taste preference.
However, the tea-ginger drink led to enhanced colour, aroma, and taste ratings.
The colour preference was found to have highest correlation coefficient with the
hue and chroma of the drinks [r(58)=-0.583, P<0.05 and r(58)=0.566, P<0.05]. This
study suggests that a sensory quality deficiency in a particular plant based
drink could be compensated for by blending the drink with another plant based
drink. This approach could help improve the uptake of plant based nutraceutical
drinks.
PMID- 29333393
TI - Effect of Monascus-Fermented Soybean Extracts on Antioxidant and Skin Aging
Related Enzymes Inhibitory Activities.
AB - We investigated the in vitro inhibitory activity against skin aging-related
enzymes and antioxidant activity of Monascus-fermented soybean extracts (MFSEs)
obtained by using different solvents. The highest Trolox equivalent (TE)
antioxidant capacity (3.13+/-0.06 mM TE/g) and oxygen radical absorbance capacity
(2.79+/-0.09 mM TE/g) of MFSEs were evaluated for the methanol and 80% ethanol
extracts, respectively. The antioxidant capacities increased with increasing
concentration (0.5~50 mg/mL). In addition, the methanol and 80% ethanol extracts
showed an effective inhibition against tyrosinase, hyaluronidase, and elastase
compared with those of acetone and hot water extracts (P<0.05). Results indicate
that the inhibitory activities against skin aging-related enzymes and antioxidant
properties provide evidence for the nutricosmetic potentials of Monascus
fermented soybeans.
PMID- 29333394
TI - Evaluation of Anti-Wrinkle Effects of DuOligo, Composed of Lactulose and
Galactooligosaccharides.
AB - Currently, alternatives to prebiotics for skin treatment are receiving much
interest. However, little is known about the efficacy of topically applied
prebiotics in skin anti-aging. This study was conducted to observe the anti-aging
effects of DuOligo, which is composed of lactulose and galactooligosaccharides
(GOS). We investigated wrinkle-related parameters by quantitative and qualitative
skin evaluation in healthy women who consumed DuOligo for 8 weeks. The double
blind, randomized, and placebo-controlled study included subjects who were
divided into two groups (Placebo: dextrin 4.5 g/d, n=14, 51.50 y vs. DuOligo:
DuOligo 4.5 g/d, n=14, 52.65 y). The DuOligo group showed a reduction in mean
wrinkle length and depth measured via quantitative skin evaluation after 8 weeks,
whereas the Placebo group showed slight increases in these parameters (P<0.001).
The wrinkle severity rating scale in the DuOligo group was decreased after 8
weeks, but it increased in the Placebo group (Placebo group: 0.14 vs. DuOligo
group: -0.86, P<0.001). The global aesthetic improvement scale for the DuOligo
group was significantly higher than that for the Placebo group at week 8
(P<0.001). In conclusion, our findings suggest that oral consumption of DuOligo
is beneficial to the skin, and present the possibility of new nutritional
strategies for wrinkle care.
PMID- 29333395
TI - IL-1B-31 and IL-1Ra polymorphisms associated with increased host susceptibility
to immune thrompocytopenia.
PMID- 29333396
TI - Unravelling the genomic landscape of leukemia using NGS techniques: the challenge
remains.
PMID- 29333397
TI - Pseudo-Chediak-Higashi inclusions in a case of acute lymphoblastic leukemia.
PMID- 29333398
TI - Myelodysplastic syndrome with occult diffuse large B-cell lymphoma.
PMID- 29333399
TI - Sinusoidal infiltration of hepatosplenic lymphoma in liver and bone marrow.
PMID- 29333400
TI - Brentuximab vedotin: clinical updates and practical guidance.
AB - Brentuximab vedotin (BV), a potent antibody-drug conjugate, targets the CD30
antigen. Owing to the remarkable efficacy shown in CD30-positive lymphomas, such
as Hodgkin's lymphoma and systemic anaplastic large-cell lymphoma, BV was granted
accelerated approval in 2011 by the US Food and Drug Administration. Thereafter,
many large-scale trials in various situations have been performed, which led to
extensions of the original indication. The aim of this review was to describe the
latest updates on clinical trials of BV and the in-practice guidance for the use
of BV.
PMID- 29333401
TI - Management of immune thrombocytopenia: Korean experts recommendation in 2017.
AB - Management options for patients with immune thrombocytopenia (ITP) have evolved
substantially over the past decades. The American Society of Hematology published
a treatment guideline for clinicians referring to the management of ITP in 2011.
This evidence-based practice guideline for ITP enables the appropriate treatment
of a larger proportion of patients and the maintenance of normal platelet counts.
Korean authority operates a unified mandatory national health insurance system.
Even though we have a uniform standard guideline enforced by insurance
reimbursement, there are several unsolved issues in real practice in ITP
treatment. To optimize the management of Korean ITP patients, the Korean Society
of Hematology Aplastic Anemia Working Party (KSHAAWP) reviewed the consensus and
the Korean data on the clinical practices of ITP therapy. Here, we report a
Korean expert recommendation guide for the management of ITP.
PMID- 29333402
TI - Interleukin-1B (IL-1B-31 and IL-1B-511) and interleukin-1 receptor antagonist (IL
1Ra) gene polymorphisms in primary immune thrombocytopenia.
AB - Background: Immune thrombocytopenia (ITP) is an immune-mediated disease caused by
autoantibodies against platelets membrane glycoproteins GPIIb/IIIa and GPIb/IX.
The etiology of ITP remains unclear. This study evaluated the association of
polymorphisms in interleukin (IL)-1B-31, IL-1B-511, and IL-1Ra with ITP. Methods:
Genotyping of IL-1B-31, IL-1B-511, and IL-1Ra was performed in 118 ITP patients
and 100 controls by polymerase chain reaction restriction fragment length
polymorphism and detection of variable number tandem repeats. Results: Genotype
differences in IL-1B-31 and IL-1Ra were significantly associated with ITP.
Patients showed a higher frequency of the IL-1B-31 variant allele (T) and a 1.52
fold greater risk of susceptibility to ITP (odds ratio [OR]=1.52, 95% confidence
interval [CI]=1.04-2.22, P=0.034). The frequencies of both homozygous and
heterozygous variant genotypes of IL-1B-31 were higher (OR=2.33, 95% CI=1.069
5.09, P=0.033 and OR=2.044, 95% CI=1.068-39, P=0.034) among patients and were
significantly associated with ITP susceptibility. Both homozygous and
heterozygous variant genotypes of IL-1Ra were also more frequent (OR=4.48, 95%
CI=1.17-17.05, P=0.0230 and OR=1.80, 95% CI=1.03-3.14, P=0.0494) among patients
and were associated with ITP risk. IL-1B-31 and IL-1Ra also showed significant
association with severe ITP. However, IL-1B-511 was not associated with ITP.
Conclusion: IL-1B-31 and IL-1Ra polymorphisms may significantly impact ITP risk,
and they could be associated with disease severity, which may contribute to the
pathogenesis of ITP.
PMID- 29333403
TI - Treatment outcomes of dose-attenuated CHOP chemotherapy in elderly patients with
peripheral T cell lymphoma.
AB - Background: While cyclophosphamide, doxorubicin, vincristine, and prednisolone
(CHOP) is the most commonly used chemotherapeutic regimen for patients with
peripheral T-cell lymphomas (PTCLs), elderly patients are more vulnerable to
associated toxicities. We evaluated the efficacy and safety of dose-attenuated
CHOP in elderly patients with PTCL. Methods: Patients with PTCL aged >70 years or
65-70-years with comorbidities were treated with dose-attenuated CHOP
(cyclophosphamide: 562.5 mg/m2, doxorubicin: 37.5 mg/m2, vincristine: 1.4 mg/m2,
and prednisolone: 100 mg for five days; 25% reduced dose of cyclophosphamide and
doxorubicin vs. full-dose CHOP) as first-line therapy were included. Results:
Forty-four patients (median age, 74 yr) were analyzed. The majority (N=42, 95.5%)
had advanced stage disease and 36 (81.8%) were classified as high/high
intermediate risk by the international prognostic index. The overall response
rate was 61.4%, and 21 patients achieved complete response (47.7%). With median
follow-up period of 28.8 months, the estimated two-year progression-free and
overall survival rates were 36.7% and 46.6%, respectively. Grade 3/4 neutropenia
and thrombocytopenia occurred in 26.9% and 7.4% of 204 total cycles, which
affected 76.7% and 25.6% of the patients, respectively. Nineteen patients (44.2%)
experienced febrile neutropenia, and six died due to treatment-related
toxicities. High lactate dehydrogenase levels and an involvement of >1 extranodal
sites were prognostic indicators of poor survival. Conclusion: Dose-attenuated
CHOP does not compromise treatment efficacy but retains significant toxicity. Our
results suggest that some patients can be effectively treated with dose
attenuated CHOP, however a novel therapy for elderly patients with PTCL is
required.
PMID- 29333404
TI - Relevance of prognostic index with beta2-microglobulin for patients with diffuse
large B-cell lymphoma in the rituximab era.
AB - Background: The International Prognostic Index (IPI) has been a useful tool for
predicting the prognosis of aggressive non-Hodgkin lymphoma in the last 20 years.
Herein, we aimed to develop a new prognostic model for diffuse large B-cell
lymphoma (DLBCL) in the rituximab era. Methods: Between March 2004 and June 2012,
patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin,
vincristine, and prednisolone chemotherapy regimen were identified in the
database of the Asan Medical Center (AMC) Lymphoma Registry. The primary and
secondary endpoints were a new prognostic index for DLBCL and validation of the
National Comprehensive Cancer Network-International Prognostic Index in our
cohort, respectively. Results: The AMC cohort comprised 621 patients. The median
follow-up duration was 43.3 months (range, 6.2-122.5 mo). Univariate analysis
revealed that age (<=60 vs. >60 yr), lactate dehydrogenase (LDH; within normal
vs. increased), Eastern Cooperative Oncology Group performance status (ECOG PS; 0
or 1 vs. >=2), advanced stage (Ann Arbor stage I/II vs. III/IV), extra-nodal
involvement (<=1 vs. >1), B symptoms (no vs. yes), and beta-2 microglobulin
(beta2MG, <=2.5 vs. >2.5) can be used to predict overall survival (OS). In
multivariate analysis, only age, LDH, ECOG performance status, and beta2MG were
significantly associated with OS, and we developed a new prognostic model with
these 4 factors. The new prognostic model showed better discriminative power
compared with the classic IPI. Conclusion: Our new prognostic index model for
DLBCL in the rituximab era has good discriminative power and is convenient to
use.
PMID- 29333405
TI - Primary central nervous system lymphoma: a new prognostic model for patients with
diffuse large B-cell histology.
AB - Background: Age and performance status are important prognostic factors in
primary central nervous system (CNS) lymphoma. Although several prognostic models
have been proposed, there is no consensus on the optimal model for patients with
diffuse large B-cell histology. Methods: Seventy-seven patients with primary CNS
diffuse large B-cell lymphoma were retrospectively analyzed to determine factors
affecting survival. Three Western models were applied to our eligible patients;
we devised a novel model based on our findings. Results: The median patient age
was 59 years (range, 29-77); the median event-free and overall survival (OS)
durations were 35.9 and 12.6 months, respectively. Nottingham/Barcelona and
Memorial Sloan Kettering Cancer Center models were applicable to our cohorts.
Multivariate analysis showed that advanced age, multifocal lesions, and high
cerebrospinal fluid (CSF) protein concentrations were correlated significantly. A
novel model for predicting prognosis was then developed based on these variables.
Each variable was assigned 1 point; patients with a total score of 0, 1, 2, and 3
were categorized into the low- (N=17), moderate- (N=26), high- (N=14), and very
high-risk groups (N=4), respectively. Sixty-one patients were eligible
considering our model; the median OS was 58.2, 34.8, 9.0, and 1.8 months in the
low-, moderate-, high-, and very high-risk groups, respectively (P<0.01).
Conclusion: Advanced age, multifocal lesions, and high CSF protein concentration
were adversely related with prognosis. Our model can be helpful in pre-treatment
risk stratification for patients with primary CNS lymphoma with diffuse large B
cell histology.
PMID- 29333406
TI - STAT3 expression is associated with poor survival in non-elderly adult patients
with newly diagnosed multiple myeloma.
AB - Background: Signal transducer and activator of transcription 3 (STAT3) is not
only a key signaling molecule in the regulation of growth but is also involved in
malignant transformation. We investigated the prognostic significance of STAT3
expression in 94 non-elderly adult patients (aged 38 to 65 yr) with newly
diagnosed multiple myeloma (MM). Methods: Tumor cell-specific phosphotyrosine
STAT3 (PY-STAT3) expression at the time of diagnosis was evaluated with dual
immunohistochemical (IHC) staining for PY-STAT3 and CD138. Results: PY-STAT3
positivity was detected in 10 patients (10.6%), including three who showed strong
expression. PY-STAT3-positive patients had higher serum C-reactive protein and
calcium levels at diagnosis than did PY-STAT3-negative patients. PY-STAT3
positivity had predictive value for poor progression-free survival (PFS; P=0.001)
and overall survival (OS; P=0.003). Among the 60 patients who received frontline
autologous stem cell transplantation, PY-STAT3-positive patients had poorer PFS
than did PY-STAT3-negative patients (4.2 vs. 19.2 mo, respectively; P=0.013).
Multivariate analysis identified PY-STAT3 expression as an independent prognostic
factor for PFS (relative risk [RR]=2.706, P=0.014) and OS (RR=3.091, P=0.044).
Conclusion: These data show that PY-STAT3 positivity, as determined using dual
IHC, is a marker of poor prognosis in non-elderly adult patients with MM.
PMID- 29333407
TI - The limited role of serum galactomannan assay in screening for invasive pulmonary
aspergillosis in allogeneic stem cell transplantation recipients on micafungin
prophylaxis: a retrospective study.
AB - Background: We evaluated the outcomes of serum galactomannan (GM) assay for the
screening of invasive pulmonary aspergillosis (IPA) in allogeneic hematopoietic
stem cell transplantation (alloHSCT) recipients while on primary antifungal
prophylaxis (PAP). Methods: This study included patients with hematologic
disorders who underwent alloHSCT from January 2013 to November 2015. Patients
received routine PAP with fluconazole before 2014 and micafungin after 2014;
serum GM tests were performed and retrospectively analyzed. The sensitivity,
specificity, positive predictive value (PPV), and negative predictive value (NPV)
of serum GM tests for detection of probable/proven IPA were evaluated. The serial
change of serum GM levels was illustrated on a time series plot. Results: A total
of 136 alloHSCT recipients at Seoul National University Hospital were included in
the study. Fluconazole was administered in 72 patients for PAP, while micafungin
was administered in the remaining 64 patients. The overall sensitivity,
specificity, and NPV of serum GM assays were 95.8% (95% confidence interval [CI]
78.9-99.9%), 93.8% (95% CI 91.7-95.5%), and 99.8% (95% CI 99.1-100.0%),
respectively. However, the PPV of GM tests was relatively low at 35.4% (95% CI
23.9-48.2%). The serial change in serum GM levels differed according to the
antifungal agents used. With effective PAP using micafungin, serial serum GM
levels showed zero order kinetics during the neutropenic period. Conclusion:
Although the serum GM assay is a sensitive and specific test for detecting IPA in
alloHSCT recipients, its role for routine surveillance in an era of effective PAP
with micafungin is limited.
PMID- 29333408
TI - Is long term storage of cryopreserved stem cells for hematopoietic stem cell
transplantation a worthwhile exercise in developing countries?
AB - Background: Stem cell units (SCUs) that are cryopreserved prior to both
autologous and allogeneic hematopoietic stem cell transplants (for donor
lymphocyte infusion) remain unused or partially used several times, and become an
increased burden to blood banks/SCU repositories. Because of the scarcity of data
regarding the duration for which the storage is useful, there is no general
consensus regarding disposal of SCUs. Methods: We conducted a retrospective audit
of SCU utilization in 435 patients who planned to undergo either autologous stem
cell transplantation (auto-SCT) (N=239) or allogeneic stem cell transplantation
(allo-SCT) (N=196) at a tertiary cancer care center between November 2007 to
January 2015. Results: Our cohort consisted of 1,728 SCUs stored for conducting
auto-SCT and 729 SCUs stored for conducting donor lymphocyte infusions (DLIs)
after allo-SCT. Stem cells were not infused in 12.5% of patients who had planned
to undergo auto-SCT, and 80% of patients who underwent allo-SCT never received
DLI. Forty-one percent of SCUs intended for use in auto-SCT remained unutilized,
with a second auto-SCT being performed only in 4 patients. Ninety-four percent of
SCUs intended for carrying out DLIs remained unused, with only minimal usage
observed one year after undergoing allo-SCT. Conclusion: The duration of storage
of unused SCUs needs to be debated upon, so that a consensus can be reached
regarding the ethical disposal of SCU.
PMID- 29333409
TI - Human parvovirus B19 and parvovirus 4 among Iranian patients with hemophilia.
AB - Background: Human parvovirus B19 (B19V) is one of the smallest DNA viruses and
shows great resistance to most disinfectants. Therefore, it is one of the common
contaminant pathogens present in blood and plasma products. Parvovirus 4 (PARV4)
is a newly identified parvovirus, which is also prevalent in parenteral
transmission. In this study, we aimed to evaluate the prevalence of B19V and
PARV4 DNA among patients with hemophilia in Birjand County in eastern Iran.
Methods: This was a cross-sectional epidemiological study comprising nearly all
people with hemophilia in this region. Whole blood samples were taken after
patient registration and sent for plasma isolation. After nucleic acid
extraction, B19V was detected with real-time polymerase chain reaction, PARV4 DNA
was then detected using sensitive semi-nested PCR. Results: In total, there were
86 patients with hemophilia, with mean age 28.5+/-1.5 years. Of these, 90.7% were
men and 9.3% women; 84.9% had hemophilia A and 7.0% had hemophilia B. We found 11
patients (12.8%) were positive for B19V DNA and 8 were positive (9.3%) for PARV4
DNA. The prevalence of B19V was higher in middle-aged groups rather than younger
people, whereas PARV4 infection was more common in younger patients (P <0.05).
Conclusion: There was a high prevalence of B19V and PARV4 infection in this high
risk group of patients with hemophilia. Due to the clinical significance of the
B19 virus, imposing more precautionary measures for serum and blood products is
recommended.
PMID- 29333410
TI - Transplantation of human umbilical cord blood CD34+ cells into the liver of
newborn NOD/SCID/IL-2Rgamma null (NSG) mice after busulfan conditioning.
PMID- 29333411
TI - Successful treatment of a patient with myelodysplastic syndrome accompanied by
pyoderma gangrenosum and Behcet's disease using allogeneic stem cell
transplantation.
PMID- 29333412
TI - Post-liver transplant myeloid maturation arrest.
PMID- 29333413
TI - A case of primary plasma cell leukemia exhibiting hemophagocytic plasma cells
relapsed with multiple cutaneous plasmacytoma.
PMID- 29333414
TI - Differential diagnosis of primary cutaneous CD4+ small/medium T-cell
lymphoproliferative lesions: A report of three cases.
PMID- 29333415
TI - A young man with acute respiratory distress syndrome: eosinophilia is not always
"benign".
PMID- 29333416
TI - Does the c.-273T>C variant in the upstream region of the HBB gene cause a
thalassemia phenotype?
PMID- 29333417
TI - Comparison of the acute erythropoietic capacities of erythropoietin and U-74389G
in terms of hemoglobin levels.
PMID- 29333418
TI - Low-dose prednisolone in patients with paroxysmal nocturnal hemoglobinuria and
inadequate response to eculizumab.
PMID- 29333419
TI - Evaluation of a polyurethane foam dressing impregnated with 3% povidone-iodine
(Betafoam) in a rat wound model.
AB - Purpose: The purpose of this study was to evaluate the efficacy of Betafoam in
terms of wound healing and safety. Methods: Fifty-four male adult Sprague-Dawley
rats (weight, 200-250 g) were used in the study. Full-thickness skin defects were
created on the back of each rats. The rats were assigned to 6 groups according to
the type of wound dressing used (n = 9 for each group): Betafoam, Allevyn-Ag,
Mepilex-Ag, Medifoam silver, Polymem-Ag, and gauze. The wound size, histological
findings, and amount of DNA on the changed dressings for each group were analyzed
and compared. Results: All groups showed an effective decrease in wound size.
However, the differences between Betafoam and the other dressings were
statistically significant on day 14 (P < 0.05). The number of newly generated
blood vessels in the Betafoam group was significantly higher than in the gauze,
Allevyn-Ag, and Medifoam silver groups (P < 0.001). In the Betafoam group, the
proportion of collagen deposition was highest and showed a significantly superior
arrangement of collagen fibers compared with the gauze, Allevyn-Ag, Mepilex-Ag,
and Medifoam silver groups. The total content of the remaining DNA counts of the
exchanged dressings were significantly lower in the Betafoam group than the
others. Conclusion: Betafoam is effective in wound healing and provides the best
performance amongst the various types of dressing materials in terms of re
epithelialization, angiogenesis, collagen deposition, and tissue invasion.
PMID- 29333420
TI - Technique for orthotopic liver transplantation in cynomolgus monkeys (Macaca
fascicularis).
AB - Purpose: Recent studies investigating new strategies to modulate the immune
system have utilized animal models of liver transplantation (LT). However, the
anhepatic phase (AHP) remains a crucial problem in LT. The aim of the present
study is to introduce a technique for successful orthotopic LT in cynomolgus
monkeys using an early-reperfusion strategy. Methods: Orthotopicallo-LT was
performed with seven donor/recipient pairs of cynomolgus monkeys. Results: In 2
recipients, liver allografts were perfused after suprahepatic inferior vena cava
(SHIVC), portal vein (PV), and infrahepatic inferior vena cava (IHIVC)
anastomosis. To reduce the time of AHP in five recipients, liver allografts ware
perfused after SHIVC and PV anastomosis while the IHIVC was not anastomosed. In
the latter strategy, the AHP was reduced from 46 minutes to 31 minutes and a 24
hour survival rate of 80% was achieved. Conclusion: Our results indicate that an
early-reperfusion strategy can be successfully used to establish a LT model in
cynomolgus monkeys with a consistently high rate of animal survival.
PMID- 29333421
TI - Brain metastasis from colorectal cancer: a single center experience.
AB - Purpose: The detection rate of brain metastasis (BM) from colorectal cancer (CRC)
is increasing. This study was designed to analyze the clinical features of BM and
prognosis according to the therapeutic modalities. Methods: A total of 19 cases
were collected in this study between November 2008 and December 2015. We reviewed
the patients' demographic data and the clinical features of BM retrospectively
and investigated their prognostic significance. Results: Nineteen patients
included 8 male and 11 female patients. The median age at diagnosis of BM was
62.4 years (range, 32-83 years). The median interval between diagnosis of CRC and
BM was 39 months (range, 0-98 months). Eighteen patients (94.7%) had extracranial
metastasis at the diagnosis of BM. Lung was the most common site of extracranial
metastasis in 14 patients (73.7%). Synchronous BMs were found at the diagnosis of
primary CRC in 2 patients (10.5%). The location of primary CRC was the colon in 6
patients (31.6%) and the rectum in 13 patients (68.4%). At the diagnosis of BM,
10 patients (52.6%) had a solitary BM. The common neurologic symptoms were
headache in 8 cases (42.1%) and ataxia in 6 cases (31.6%). The median survival
after the diagnosis of BM was 3 months (range, 1-10 months). The patients who
underwent surgery plus stereotactic radiosurgery (SRS) had an improved survival
(range, 3-10 months) than the other patients (range, 1-6 months) (P = 0.016).
Conclusion: In patients with BM from CRC, surgical resection plus SRS might
improve survival.
PMID- 29333422
TI - Epigenetic inactivation of RUNX3 in colorectal cancer.
AB - Purpose: Emerging evidence indicates that runt-related transcription factor 3
(RUNX3) is an important tumor suppressor gene in several cancer types, including
colorectal cancer (CRC). However, the clinical significance of RUNX3 inactivation
in CRC remains unclear. The aim of this study was to examine the correlation
between clinicopathologic factors and RUNX3 hypermethylation/expression in CRC.
Methods: Sixty-two CRC patients who were treated at the Soonchunhyang University
College of Medicine were recruited in this study. The hypermethylation of CpG
islands in the RUNX3 promoter and the expression of RUNX3 mRNA were identified by
methylation-specific polymerase chain reaction (PCR) and reverse transcriptase
PCR, respectively. The expression of RUNX3 was determined by immunohistochemical
staining. Results: Of the 62 CRC tissue samples, 20 (32.3%) presented
hypermethylated RUNX3 promoters. Aberrant RUNX3 hypermethylation was found to be
associated with vascular (P = 0.006) and lymphatic (P = 0.002) invasion.
Hypermethylation of RUNX3 was associated with poor survival outcomes (P = 0.038).
However, expression of RUNX3 was not a prognostic factor (P = 0.363). Conclusion:
Hypermethylation of RUNX3 may be a predictor of a poor prognosis in CRC.
PMID- 29333423
TI - Long-term outcomes after Natural Orifice Specimen Extraction versus conventional
laparoscopy-assisted surgery for rectal cancer: a matched case-control study.
AB - Purpose: The aim of this study was to compare the long-term outcomes of total
laparoscopic surgery with Natural Orifice Specimen Extraction (NOSE) with those
for conventional laparoscopy (CL)-assisted surgery for treating rectal cancers.
Methods: We reviewed the prospectively collected records of 844 patients (163
NOSE and 681 CL) who underwent curative surgery for mid- or upper rectal cancers
from January 2006 to November 2012. We applied propensity score analyses and
compared oncological outcomes for the NOSE and CL groups in a 1:1 matched cohort.
Results: After propensity score matching, each group included 138 patients; the
NOSE and CL groups did not differ significantly in terms of baseline clinical
characteristics. The median follow-up was 57.7 months (interquartile range, 42.4
82.5 months). The combined 5-year local recurrence rate for all tumor stages was
4.1% (95% confidence interval [CI], 0.9%-7.4%) in the NOSE group and 3.0% (95%
CI, 0%-6.3%) in the CL group (P = 0.355). The combined 5-year disease-free
survival rates for all stages were 89.3% (95% CI, 84.3%-94.3%) in the NOSE group
and 87.3% (95% CI, 81.8%-92.9%) in the CL group (P = 0.639). The postoperative
mean fecal incontinence scores at 6, 12, and 24 months were similar between the 2
groups. Conclusion: In our experience, NOSE for mid- and upper rectal cancer had
acceptable long-term oncologic outcomes comparable to those of conventional
minimal invasive surgery and seems to be a safe alternative to reduce access
trauma.
PMID- 29333424
TI - Anatomical distribution and detection rate of colorectal neoplasms according to
age in the colonoscopic screening of a Korean population.
AB - Purpose: Because data as a basis for the determination of proper age and modality
for screening of colorectal neoplasms is lacking, we evaluated detection rates
and anatomical distribution of colorectal neoplasms according to age in healthy
individuals who underwent total colonoscopy for health checkup. Methods: A total
of 16,100 cases that had received the colonoscopic examination from January to
December in 2014 were analyzed. The total number of individuals who received
total colonoscopy were divided by the number of individuals harboring colorectal
adenoma to calculate the detection rate of colorectal adenoma. Individuals <=50
years old were classified as young-age group and aged >50 were old-age group.
Differences in anatomical locations of colorectal neoplasms were analyzed in the
2 age groups by chi-square test. Risk factors for colorectal adenoma in each age
group were analyzed using univariate and multivariate logistic regression
analyses. Results: Detection rates of colorectal adenoma were 13.7% in all cases
and 12.8% for those in their 40's. The main anatomical location of colorectal
adenoma was proximal colon in both age groups (P < 0.001). Hyperplastic polyp was
mainly distributed to the distal colon in both age groups (P < 0.001). Distal
colon was the major site for colorectal cancer in the old-age group (P = 0.001).
Proximal location of neoplasms was a risk factor for colorectal adenoma in both
age groups with multivariate analysis. Conclusion: These data could be the bases
for earlier initiation of screening for colorectal neoplasms with total
colonoscopy to detect clinically significant colorectal polyps.
PMID- 29333425
TI - Outcomes of selective surgery in patients with suspected small bowel injury from
blunt trauma.
AB - Purpose: The role of initial conservative therapy with selective surgery for
patients with suspected blunt bowel injury by radiologic evaluation is less
clear. The aim of the study is to assess the outcomes of patients who received
initial conservative therapy with selective delayed surgery, compared to
emergency surgery. Methods: During this 8-year study, a total of 77 patients who
were hemodynamically stable were enrolled, in which computed tomography verified
suspected bowel injury from blunt trauma (mesenteric hematoma, mesenteric fat
infiltration, bowel wall thickening, and free fluid without solid organ injury)
was managed with either initial conservative therapy with selective delayed
surgery (group A; n = 42) or emergency surgery (group B; n = 35). The clinical
outcomes including the rate of negative or nontherapeutic exploration and
postoperative complications, between the groups were compared. Results: The
enrolled patients had a mean age of 41 years including 51 men and 26 women. No
difference in the clinical characteristics was found between the groups. In group
A, 18 patients underwent delayed surgery and 24 recovered without surgery. Among
patients who underwent surgery, 3 (17%) underwent negative or nontherapeutic
explorations. In group B, 13 (37%) underwent negative or nontherapeutic
explorations. Postoperative complications occurred in 21 patients and there was
no difference between the groups. Conclusion: Initial conservative therapy with
selective delayed surgery did not increased severe postoperative complications
and had a low rate of negative or nontherapeutic surgical explorations in
hemodynamically stable patients with suspected blunt bowel injury.
PMID- 29333427
TI - Surgery of multiple lymphangioma in small bowel: a rare case report of chronic
gastrointestinal bleeding.
AB - Small bowel lymphangioma is a rare benign tumor of the lymphatic system,
characterized by the presence of dilated lymphatic spaces and significant
gastrointestinal bleeding. Small bowel lymphangiomas are rare in adults and case
reports are few. Lymphangiomas in the jejunum or ileum are extremely rare and
account for less than 1% of all lymphangiomas. The case reported herein is of an
older patient (70-year-old male) with melena and chronic anemia (hemoglobin count
< 5 g/dL) who had small-sized multiple lymphangiomas in his small bowel
(jejunum). Surgical resection was performed after failure of treatment by
gastroenteroscopy. Final pathological analysis revealed lymphangioma with
thrombus and hemorrhage. After surgery, he no longer had decreased hemoglobin
count, nor symptoms of anemia and melena. Also, at the last follow-up visit, the
patient's hemoglobin count patient was normal and he returned to normal daily
functions.
PMID- 29333426
TI - Are you prepared for pancreas bifidum? A case report.
AB - Pancreas divisum-failure of fusion of the dorsal and ventral pancreatic ducts-is
relatively well known as the most common congenital anomaly of the pancreatic
duct, of with an incidence approximately 10% of all embryos. And there is a rare
anomaly similar to pancreas divisum in which doubled ducts are formed. This
condition is a rare developmental anomaly called pancreas bifidum or bifid
pancreas or fish tail pancreas. This report describes a patient with pancreas
bifidum who had 2 separated ducts within the pancreas from tail to neck but did
not have a separated parenchyma. We hope that this report helps pancreatic
surgeons to have knowledge of pancreas bifidum and helps them to be prepared for
this anatomical variant.
PMID- 29333428
TI - The Effect of Prucalopride on Small Bowel Transit Time in Hospitalized Patients
Undergoing Capsule Endoscopy.
AB - Background: The inpatient status is a well-known risk factor for incomplete video
capsule endoscopy (VCE) examinations due to prolonged transit time. We aimed to
evaluate the effect of prucalopride on small bowel transit time for hospitalized
patients undergoing VCE. Methods: We included all hospitalized patients who
underwent VCE at a tertiary academic center from October 2011 through September
2016. A single 2 mg dose of prucalopride was given exclusively for all patients
who underwent VCE between March 2014 and December 2015. VCE studies were excluded
if the capsule was retained or endoscopically placed, if other prokinetic agents
were given, in cases with technical failure, or if patients had prior gastric or
small bowel resection. Results: 442 VCE were identified, of which 68 were
performed in hospitalized patients. 54 inpatients were included, of which 29
consecutive patients received prucalopride. The prucalopride group had a
significantly shorter small bowel transit time compared to the control group (92
versus 275.5, p < 0.001). There was a trend for a higher completion rate in the
prucalopride group (93.1% versus 76%, p = 0.12). Conclusions: Our results suggest
that the administration of prucalopride prior to VCE is a simple and effective
intervention to decrease small bowel transit time.
PMID- 29333429
TI - Screening of Lipid Composition for Scalable Fabrication of Solvent-Free Lipid
Microarrays.
AB - Liquid microdroplet arrays on surfaces are a promising approach to the
miniaturization of laboratory processes such as high-throughput screening. The
fluid nature of these droplets poses unique challenges and opportunities in their
fabrication and application, particularly for the scalable integration of
multiple materials over large areas and immersion into cell culture solution.
Here, we use pin spotting and nanointaglio printing to screen a library of lipids
and their mixtures for their compatibility with these fabrication processes, as
well as stability upon immersion into aqueous solution. More than 200
combinations of natural and synthetic oils composed of fatty acids,
triglycerides, and hydrocarbons were tested for their pin-spotting and
nanointaglio print quality and their ability to contain the fluorescent compound
tetramethylrhodamine B isothiocyanate (TRITC) upon immersion in water. A
combination of castor oil and hexanoic acid at the ratio of 1:1 (w/w) was found
optimal for producing reproducible patterns that are stable upon immersion into
water. This method is capable of large-scale nanomaterials integration.
PMID- 29333432
TI - Cytomegalovirus-associated pulmonary exacerbation in patients with cystic
fibrosis.
AB - CMV is an unusual cause of pulmonary exacerbation in immunocompetent individuals
with CF http://ow.ly/Rdds30hlnjV.
PMID- 29333431
TI - Morphology Changes in Human Fungal Pathogens upon Interaction with the Host.
AB - Morphological changes are a very common and effective strategy for pathogens to
survive in the mammalian host. During interactions with their host, human
pathogenic fungi undergo an array of morphological changes that are tightly
associated with virulence. Candida albicans switches between yeast cells and
hyphae during infection. Thermally dimorphic pathogens, such as Histoplasma
capsulatum and Blastomyces species transform from hyphal growth to yeast cells in
response to host stimuli. Coccidioides and Pneumocystis species produce spherules
and cysts, respectively, which allow for the production of offspring in a
protected environment. Finally, Cryptococcus species suppress hyphal growth and
instead produce an array of yeast cells-from large polyploid titan cells to micro
cells. While the morphology changes produced by human fungal pathogens are
diverse, they all allow for the pathogens to evade, manipulate, and overcome host
immune defenses to cause disease. In this review, we summarize the morphology
changes in human fungal pathogens-focusing on morphological features, stimuli,
and mechanisms of formation in the host.
PMID- 29333433
TI - Vitamin D Receptor Gene Polymorphisms Influence T1D Susceptibility among
Pakistanis.
AB - Background: The vitamin D receptor (VDR) gene regulates insulin secretion from
the pancreas and acts as a mediator of the immune response through vitamin D.
Polymorphism in VDR causes alterations in the functioning of vitamin D, leading
to type 1 diabetes (T1D) predisposition. The aim of the present study was to
determine VDR gene polymorphism in association with T1D in Pakistanis. Methods:
The association was evaluated by selecting rs2228570 (FokIota), rs7975232
(ApaIota), and rs731236 (TaqIota) polymorphic sites in 102 patients and 100
controls. Genotypes were identified by DNA sequencing and PCR-RFLP. Results: The
allelic and genotypic frequencies of FokIota and ApaI were significantly
associated with T1D (p < 0.001) development. At the FokIota site, tryptophan was
replaced with arginine due to polymorphism. A novel SNP (GeneBank acc number
KT280406) was identified through the sequencing of intron 8, 62 bp downstream
from the ApaI polymorphic site, and significantly associated with T1D
development. The TaqIota did not depict any association with T1D at the allelic
or genotypic level (p > 0.05). CCGC, CCGG, CCTC, and CCTG haplotypes were
significantly associated with disease development (p < 0.05). However, CTGG
haplotype was protective towards T1D (p < 0.01). Conclusion: VDR polymorphisms
were identified as susceptible regions for T1D development in the Pakistani
population.
PMID- 29333430
TI - Adaptive Immunity to Cryptococcus neoformans Infections.
AB - The Cryptococcus neoformans/Cryptococcus gattii species complex is a group of
fungal pathogens with different phenotypic and genotypic diversity that cause
disease in immunocompromised patients as well as in healthy individuals. The
immune response resulting from the interaction between Cryptococcus and the host
immune system is a key determinant of the disease outcome. The species C.
neoformans causes the majority of human infections, and therefore almost all
immunological studies focused on C. neoformans infections. Thus, this review
presents current understanding on the role of adaptive immunity during C.
neoformans infections both in humans and in animal models of disease.
PMID- 29333435
TI - Enhancement of Nucleoside Production in Hirsutella sinensis Based on Biosynthetic
Pathway Analysis.
AB - To enhance nucleoside production in Hirsutella sinensis, the biosynthetic
pathways of purine and pyrimidine nucleosides were constructed and verified. The
differential expression analysis showed that purine nucleoside phosphorylase,
inosine monophosphate dehydrogenase, and guanosine monophosphate synthase genes
involved in purine nucleotide biosynthesis were significantly upregulated 16.56
fold, 8-fold, and 5.43-fold, respectively. Moreover, dihydroorotate
dehydrogenase, uridine nucleosidase, uridine/cytidine monophosphate kinase, and
inosine triphosphate pyrophosphatase genes participating in pyrimidine nucleoside
biosynthesis were upregulated 4.53-fold, 10.63-fold, 4.26-fold, and 5.98-fold,
respectively. To enhance the nucleoside production, precursors for synthesis of
nucleosides were added based on the analysis of biosynthetic pathways. Uridine
and cytidine contents, respectively, reached 5.04 mg/g and 3.54 mg/g when adding
2 mg/mL of ribose, resulting in an increase of 28.6% and 296% compared with the
control, respectively. Meanwhile, uridine and cytidine contents, respectively,
reached 10.83 mg/g 2.12 mg/g when adding 0.3 mg/mL of uracil, leading to an
increase of 176.3% and 137.1%, respectively. This report indicated that
fermentation regulation was an effective way to enhance the nucleoside production
in H. sinensis based on biosynthetic pathway analysis.
PMID- 29333437
TI - A Key Major Guideline for Engineering Bioactive Multicomponent
Nanofunctionalization for Biomedicine and Other Applications: Fundamental Models
Confirmed by Both Direct and Indirect Evidence.
AB - This paper deals with the engineering multicomponent nanofunctionalization
process considering fundamental physicochemical features of nanostructures such
as surface energy, chemical bonds, and electrostatic interactions. It is pursued
by modeling the surface nanopatterning and evaluating the proposed technique and
the models. To this end, the effects of surface modifications of nanoclay on
surface interactions, orientations, and final features of TiO2/Mt nanocolloidal
textiles functionalization have been investigated. Various properties of cross
linkable polysiloxanes (XPs) treated samples as well as untreated samples with
XPs have been compared to one another. The complete series of samples have been
examined in terms of bioactivity and some physical properties, given to provide
indirect evidence on the surface nanopatterning. The results disclosed a key role
of the selected factors on the final features of treated surfaces. The effects
have been thoroughly explained and modeled according to the fundamental
physicochemical features. The developed models and associated hypotheses
interestingly demonstrated a full agreement with all measured properties and were
appreciably confirmed by FESEM evidence (direct evidence). Accordingly, a
guideline has been developed to facilitate engineering and optimizing the pre-,
main, and post-multicomponent nanofunctionalization procedures in terms of
fundamental features of nanostructures and substrates for biomedical applications
and other approaches.
PMID- 29333436
TI - Behavioural and Autonomic Regulation of Response to Sensory Stimuli among
Children: A Systematic Review of Relationship and Methodology.
AB - Background: Previous studies have explored the correlates of behavioural and
autonomic regulation of response to sensory stimuli in children; however, a
comprehensive review of such relationship is lacking. This systematic review was
performed to critically appraise the current evidence on such relationship and
describe the methods used in these studies. Methods: Online databases were
systematically searched for peer-reviewed, full-text articles in the English
language between 1999 and 2016, initially screened by title and abstract, and
appraised and synthesized by two independent review authors. Results: Fourteen
Level III-3 cross-sectional studies were included for systematic review, among
which six studies explored the relationship between behaviour and physiological
regulation of responses to sensory stimuli. Three studies reported significant
positive weak correlations among ASD children; however, no correlations were
found in typically developing children. Methodological differences related to
individual differences among participants, measures used, and varied laboratory
experimental setting were noted. Conclusion: This review suggests inconclusive
evidence supporting the relationship between behavioural and physiological
regulation of responses to sensory stimuli among children. Methodological
differences may likely have confounded the results of the current evidence. We
present methodological recommendations to address this matter for future
researches. This trial is registered with PROSPERO registration number
CRD42016043887.
PMID- 29333434
TI - CONSERVED AND EXAPTED FUNCTIONS OF NUCLEAR RECEPTORS IN ANIMAL DEVELOPMENT.
AB - The nuclear receptor gene family includes 18 members that are broadly conserved
among multiple disparate animal phyla, indicating that they trace their
evolutionary origins to the time at which animal life arose. Typical nuclear
receptors contain two major domains: a DNA-binding domain and a C-terminal domain
that may bind a lipophilic hormone. Many of these nuclear receptors play varied
roles in animal development, including coordination of life cycle events and
cellular differentiation. The well-studied genetic model systems of Drosophila,
C. elegans, and mouse permit an evaluation of the extent to which nuclear
receptor function in development is conserved or exapted (repurposed) over animal
evolution. While there are some specific examples of conserved functions and
pathways, there are many clear examples of exaptation. Overall, the evolutionary
theme of exaptation appears to be favored over strict functional conservation.
Despite strong conservation of DNA-binding domain sequences and activity, the
nuclear receptors prove to be highly-flexible regulators of animal development.
PMID- 29333438
TI - Effect of Endogenous Arginine-Vasopressin Arising from the Paraventricular
Nucleus on Learning and Memory Functions in Vascular Dementia Model Rats.
AB - The hippocampus is a key structure for encoding and processing memory and for
spatial orientation, which are among the cognitive functions most sensitive to
cerebral ischemia, hypoxia, and vascular dementia (VD). Since hippocampal
formation is one of the principle forebrain targets for arginine-vasopressin
(AVP) innervations arising in the hypothalamic paraventricular nucleus (PVN), we
explored the contributions of AVP to VD pathogenesis. To this end, we randomly
assigned pathogen-free, male Wistar rats to one of seven groups in a VD model and
tested AVP treatment effects on spatial learning and memory using the Morris
water maze. We also measured the superoxide dismutase (SOD) activity and
malondialdehyde (MDA) concentration in brain samples and monitored the expression
of AVP-positive neurons in the hippocampus by immunohistochemistry. The VD model
with repeated cerebral ischemia-reperfusion injury evoked impairment of cognitive
function and reduced cerebral concentrations of the antioxidation markers.
Lesioning the rat PVN showed a similar effect on learning and memory and reduced
antioxidation markers in the brain tissue. However, AVP injection into the PVN
improved cognitive performance in VD rats, while enhancing/rectifying the changes
in antioxidation markers. We conclude that our VD model may decrease AVP
secretion in the PVN and subsequently reduce antioxidant capacity in the
hippocampus, leading to impaired cognitive function.
PMID- 29333439
TI - Cloning, Expression, and Immunogenicity of Fimbrial-F17A Subunit Vaccine against
Escherichia coli Isolated from Bovine Mastitis.
AB - There is a need to identify and select new promising immunodominant antigens that
have the ability to provide protective immunity against E. coli causing bovine
mastitis. Recently we showed that f17a was found to be the most prevalent and
crucial virulent factor among the pathogenic E. coli isolated from bovine
mastitis. Here, in this report, the recombinant F17A based subunit vaccine
adjuvant with MF59 was tested for immunogenicity against E. coli in a murine
model. The vaccinated mice did not show any abnormal behavioral changes and
histopathological lesions after vaccination. The specific antibody level against
F17A was significantly higher in MF59-adjuvant-group, and also lasted for longer
duration with a significant (P < 0.01) production level of IgG1 and IgG2a.
Moreover, we noted higher survival rate in mice injected with F17A-MF59-adjuvant
group after challenging with the clinical E. coli strain. Our findings of
bacterial clearance test revealed that elimination rate from liver, spleen, and
kidney in MF59-adjuvant-group was significantly higher than the control group.
Finally, the proportion of CD4+T cells was increased, while CD8+ was decreased in
MF59-adjuvant group. In conclusion, the current study reveals the capability of
F17A-MF59 as a potential vaccine candidate against pathogenic E. coli causing
mastitis in dairy animals.
PMID- 29333440
TI - Erratum to "Collagen Sponge Functionalized with Chimeric Anti-BMP-2 Monoclonal
Antibody Mediates Repair of Critical-Size Mandibular Continuity Defects in a
Nonhuman Primate Model".
AB - [This corrects the article DOI: 10.1155/2017/8094152.].
PMID- 29333441
TI - Corrigendum to "Safety and Clinical Usage of Newcastle Disease Virus in Cancer
Therapy".
AB - [This corrects the article DOI: 10.1155/2011/718710.].
PMID- 29333442
TI - Characterisation of Casein Kinase 1.1 in Leishmania donovani Using the CRISPR
Cas9 Toolkit.
AB - The recent adaptation of CRISPR Cas9 genome editing to Leishmania spp. has opened
a new era in deciphering Leishmania biology. The method was recently improved
using a PCR-based CRISPR Cas9 approach, which eliminated the need for cloning.
This new approach, which allows high-throughput gene deletion, was successfully
validated in L. mexicana and L. major. In this study, we validated the toolkit in
Leishmania donovani targeting the flagellar protein PF16, confirming that the
tagged protein localizes to the flagellum and that null mutants lose their
motility. We then used the technique to characterise CK1.1, a member of the
casein kinase 1 family, which is involved in the regulation of many cellular
processes. We showed that CK1.1 is a low-abundance protein present in
promastigotes and in amastigotes. We demonstrated that CK1.1 is not essential for
promastigote and axenic amastigote survival or for axenic amastigote
differentiation, although it may have a role during stationary phase. Altogether,
our data validate the use of PCR-based CRISPR Cas9 toolkit in L. donovani, which
will be crucial for genetic modification of hamster-derived, disease-relevant
parasites.
PMID- 29333443
TI - Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Activates Type I Interferon
Signals in Lupus Nephritis.
AB - Type I interferon (IFN) plays a central role in pathogenesis of systemic lupus
erythematosus (SLE); tumor necrosis factor-like weak inducer of apoptosis (TWEAK)
has been associated with a pathogenic role in lupus nephritis (LN). Thus we
investigated whether TWEAK could induce the activation of type I IFN pathway in
LN. We examined this in patient-derived peripheral blood mononuclear cells
(PBMCs) as well as MRL/lpr mice, a murine LN model. Relative to the control
cohorts, MRL/lpr mice showed severe histological changes, high index levels of
renal damage, and elevated expression of type I IFN-inducible genes. After shRNA
suppression of TWEAK, we observed that renal damage was significantly attenuated
and expression of type I IFN-inducible genes was reduced in MRL/lpr mice. In
parallel, siRNA of TWEAK also significantly reduced the expression of type I IFN
inducible genes in PBMCs relative to control transfections. In PBMCs, TWEAK
stimulation also led to expression of type I IFN-inducible genes. Our results
illustrate a novel regulatory role of TWEAK, in which its activity positively
regulates type I IFN pathway in LN based on preclinical models. Our findings
suggest TWEAK could act as a critical target in preventing renal damage in
patients with LN.
PMID- 29333444
TI - MicroRNA-31 Function as a Suppressor Was Regulated by Epigenetic Mechanisms in
Gastric Cancer.
AB - Gastric cancer is one of the most lethal malignancies worldwide. The aberrant
expression of microRNA-31 (miR-31) has been reported in gastric cancer; however,
its regulation mechanisms are still unclear. Here, we confirmed that miR-31
expression was significantly decreased in gastric cancer tissue and cell lines.
Ectopic expression of miR-31 potentially suppresses proliferation and induced
early apoptosis in gastric cancer cells. Furthermore, miR-31 expression was
regulated as a result of epigenetic mechanisms. The downregulation of miR-31 was
associated with promoter DNA methylation status in gastric cancer and cell lines.
Moreover, we found that HDAC2 was the direct target of miR-31 by binding to 3'
UTR from the results of luciferase reporter assays, qRT-PCR, and western
blotting. HDAC2 played an activation role in tumor growth, whose expression is
upregulated and inversely associated with miR-31 levels. All the results
suggested that miR-31 function as a crucial tumor suppressor was regulated by
epigenetic mechanisms in gastric cancer. We found an epigenetic pathway loop, DNA
methylation-miRNA expression-target gene-tumor progression in gastric cancer, and
also provided implications for molecular diagnosis and therapeutics of gastric
malignancies by detecting miR-31 as a potential target.
PMID- 29333445
TI - Retrograde Activation of the Extrinsic Apoptotic Pathway in Spinal-Projecting
Neurons after a Complete Spinal Cord Injury in Lampreys.
AB - Spinal cord injury (SCI) is a devastating condition that leads to permanent
disability because injured axons do not regenerate across the trauma zone to
reconnect to their targets. A prerequisite for axonal regeneration will be the
prevention of retrograde degeneration that could lead to neuronal death. However,
the specific molecular mechanisms of axotomy-induced degeneration of spinal
projecting neurons have not been elucidated yet. In lampreys, SCI induces the
apoptotic death of identifiable descending neurons that are "bad
regenerators/poor survivors" after SCI. Here, we investigated the apoptotic
process activated in identifiable descending neurons of lampreys after SCI. For
this, we studied caspase activation by using fluorochrome-labeled inhibitors of
caspases, the degeneration of spinal-projecting neurons using Fluro-Jade C
staining, and the involvement of the intrinsic apoptotic pathway by means of
cytochrome c and Valpha double immunofluorescence. Our results provide evidence
that, after SCI, bad-regenerating spinal cord-projecting neurons slowly
degenerate and that the extrinsic pathway of apoptosis is involved in this
process. Experiments using the microtubule stabilizer Taxol showed that caspase-8
signaling is retrogradely transported by microtubules from the site of axotomy to
the neuronal soma. Preventing the activation of this process could be an
important therapeutic approach after SCI in mammals.
PMID- 29333446
TI - Adaptation and Validation of the Foot Function Index-Revised Short Form into
Polish.
AB - Purpose: The aim of the present study was to adapt the Foot Function Index
Revised Short Form (FFI-RS) questionnaire into Polish and verify its reliability
and validity in a group of patients with rheumatoid arthritis (RA). Methods: The
study included 211 patients suffering from RA. The FFI-RS questionnaire underwent
standard linguistic adaptation and its psychometric parameters were investigated.
The enrolled participants had been recruited for seven months as a convenient
sample from the rheumatological hospital in Srem (Poland). They represented
different sociodemographic characteristics and were characterized as rural and
city environments residents. Results: The mean age of the patients was 58.9 +/-
10.2 years. The majority of patients (85%) were female. The average final FFI-RS
score was 62.9 +/- 15.3. The internal consistency was achieved at a high level of
0.95 in Cronbach's alpha test, with an interclass correlation coefficient ranging
between 0.78 and 0.84. A strong correlation was observed between the FFI-RS and
Health Assessment Questionnaire-Disability Index (HAQ-DI) questionnaires.
Conclusion: The Polish version of FFI-RS-PL indicator is an important tool for
evaluating the functional condition of patients' feet and can be applied in the
diagnosis and treatment of Polish-speaking patients suffering from RA.
PMID- 29333447
TI - Comparison of Different Contrast Agents in Detecting Cardiac Right-to-Left Shunt
in Patients with a Patent Foramen Ovale during Contrast-Transthoracic
Echocardiography.
AB - The aim of this study is to evaluate the ability of two different contrast agents
to detect cardiac right-to-left shunting in patients with a patent foramen ovale
during contrast transthoracic echocardiography and transesophageal
echocardiography. Eighty-four patients who had migraines or experienced
cryptogenic stroke were prospectively enrolled. Contrast echocardiography of the
right portion of the heart was performed using an injection of either (i) 8 ml of
agitated saline, 1 ml of blood, and 1 ml of air (ASB) or (ii) 4 ml of vitamin B6
and 6 ml of sodium bicarbonate solution (VSBS). All patients underwent contrast
echocardiography with different contrast agents successively before undergoing
transesophageal echocardiography. The diagnostic sensitivity of VSBS and ASB for
cardiac shunting diagnosis was 94.23% and 78.85%, respectively. The diagnostic
sensitivity in the VSBS group was significantly higher than that in the ASB group
(chi2 = 5.283, P = 0.022). The observed semiquantitative shunt grading suggests
that the positive rate in the VSBS group was higher than that in the ASB group (Z
= -1.998, P = 0.046). The use of vitamin B6 and sodium bicarbonate solution as a
TTE contrast agent yielded a high sensitivity compared with ASB. However, further
trials with large sample size are required to confirm this finding.
PMID- 29333448
TI - Comparison of Monolateral External Fixation and Internal Fixation for Skeletal
Stabilisation in the Management of Small Tibial Bone Defects following Successful
Treatment of Chronic Osteomyelitis.
AB - Background: To compare the salvage rate and complication between internal
fixation and external fixation in patients with small bone defects caused by
chronic infectious osteomyelitis debridement. Methods: 125 patients with chronic
infectious osteomyelitis of tibia fracture who underwent multiple irrigation,
debridement procedure, and local/systemic antibiotics were enrolled. Bone
defects, which were less than 4 cm, were treated with bone grafting using either
internal fixation or monolateral external fixation. 12-month follow-up was
conducted with an interval of 3 months to evaluate union of bone defect. Results:
Patients who underwent monolateral external fixation had higher body mass index
and fasting blood glucose, longer time since injury, and larger bone defect
compared with internal fixation. No significant difference was observed in
incidence of complications (23.5% versus 19.3%), surgery time (156 +/- 23 minutes
versus 162 +/- 21 minutes), and time to union (11.1 +/- 3.0 months versus 10.9 +/
3.1 months) between external fixation and internal fixation. Internal fixation
had no significant influence on the occurrence of postoperation complications
after multivariate adjustment when compared with external fixation. Furthermore,
patients who underwent internal fixation experienced higher level of daily living
scales and lower level of anxiety. Conclusions: It was relatively safe to use
internal fixation for stabilization in osteomyelitis patients whose bone defects
were less than 4 cm and infection was well controlled.
PMID- 29333449
TI - The Root Membrane Technique: Human Histologic Evidence after Five Years of
Function.
AB - Background: The "root membrane" (RM) is a technique that has become popular among
implantologists for placement of immediate implants in the anterior maxilla.
Purpose: To present histologic evidence of an immediate implant placed in the
human anterior maxilla, according to the RM technique, and retrieved after five
years. Methods: A fixture, along with the surrounding tissues, was retrieved from
the anterior maxilla of a 68-year-old patient, who had been treated five years
earlier with immediate implant placement and RM technique. The specimen was
processed for histologic/histomorphometric evaluation. Results: The buccal bone
plate was maintained without any resorption; a healthy periodontal ligament was
evidenced. The implant showed osseointegration, with a high percentage of bone-to
implant contact (BIC = 76.2%). With regard to the space between the RM and the
implant, the apical and medial thirds were filled with compact, mature bone; the
coronal third was colonized by noninfiltrated connective tissue. Conclusions: The
RM technique appears to be effective in preventing bone resorption of the buccal
bone plate of the human anterior maxilla, five years after the placement of an
immediate implant.
PMID- 29333450
TI - RBP4: A Culprit for Insulin Resistance in End Stage Renal Disease That Can Be
Cleared by Hemodiafiltration.
AB - Introduction: Retinol Binding Protein 4 (RBP4) is mainly excreted by the kidney
and plays a pivotal role in insulin resistance (IR). In our study, we evaluated
the association between RBP4 and IR in hemodialysis subjects (HD). We also
assessed how circulating RBP4 could be influenced by kidney transplant or
different dialytic techniques. Methods: RBP4 serum levels were evaluated in HD (n
= 16) and matched healthy controls (C; n = 16). RBP4 and glucose transporter type
4 (GLUT4) mRNA expressions were also determined in adipose tissue. Circulating
RBP4 was evaluated after kidney transplant (n = 7) and in hemodialysis patients
(n = 10) enrolled in a cross-over study treated with standard bicarbonate
dialysis (BD) or hemodiafiltration (HDF). Results: HOMA index (P < 0.05) and
serum RBP4 (P < 0.005) were higher in HD compared to C. RBP4 levels positively
correlated with fasting serum glucose (P < 0.05). RBP4 mRNA was lower in HD
compared to C (P < 0.05) and positively correlated with kidney function (P <
0.05) and GLUT4 mRNA (P < 0.001). Transplant or HDF reduced circulating RBP4 (P <
0.01 and P < 0.05, resp.). Our results demonstrate that IR is associated with
high circulating RBP4 and that suppressed RBP4 adipose tissue expression is
accompanied by reduced GLUT4 expression in HD. Renal transplantation or HDF are
effective in lowering serum RBP4 levels.
PMID- 29333452
TI - Jail Diversion for Persons with Serious Mental Illness Coordinated by a
Prosecutor's Office.
AB - Persons with serious mental illnesses (SMI) are involved in the criminal justice
system at a disproportionately higher rate than the general population. While the
exact causes remain unclear, it is accepted that a comprehensive strategy
including mental health treatment is needed to reduce recidivism. This paper
describes a unique jail diversion program coordinated by a county prosecutor's
office in which individuals were diverted towards mental health services
including case management, community-based services, and housing supports.
Outcomes were studied over a five-year period, beyond the typical 12- to 24-month
follow-up in other studies. Individuals who completed the program, compared to
those who did not complete it, were at lower risk for being rearrested, arrested
fewer times, and incarcerated fewer days. Gains were moderated by previous
criminal justice involvement and substance use but, nevertheless, were maintained
despite severity of history. The strongest gains were seen while the individual
was still actively enrolled in the diversion services and these outcomes were
maintained for up to four years. These findings suggest that completion of a jail
diversion program facilitated by a prosecutor's office can lower recidivism and
days incarcerated. Further research is needed to assess the unique contribution
of prosecutor office facilitation.
PMID- 29333451
TI - Purification, Characterization, and Mode of Action of Pentocin JL-1, a Novel
Bacteriocin Isolated from Lactobacillus pentosus, against Drug-Resistant
Staphylococcus aureus.
AB - Staphylococcus aureus and its drug-resistant strains, which threaten public
health and food safety, are in need of effective control by biopreservatives. A
novel bacteriocin, pentocin JL-1, produced by Lactobacillus pentosus that was
isolated from the intestinal tract of Chiloscyllium punctatum, was purified by a
four-step chromatographic process. Mass spectrometry based on MALDI-TOF indicated
that pentocin JL-1 has a molecular mass of 2987.23 Da. Only six of the twenty
five amino acids could be identified by Edman degradation. This bacteriocin is
thermostable and tolerates a pH range of 5-7. Also, it is sensitive to proteinase
K, trypsin, pepsin, and alkaline protease. This bacteriocin has a broad
inhibitory spectrum against both Gram-positive and Gram-negative strains and in
particular is effective against multidrug-resistant S. aureus. Additionally, we
showed that the cell membrane is the target of pentocin JL-1 against methicillin
resistant S. aureus (MRSA), causing a loss of proton motive force. Furthermore,
pentocin JL-1 has a drastic impact on the structure and integrity of MRSA cells.
These results suggest that pentocin JL-1 has potential as a biopreservative in
the food industry.
PMID- 29333453
TI - Hibiscus syriacus Extract from an Established Cell Culture Stimulates Skin Wound
Healing.
AB - Higher plants are the source of a wide array of bioactive compounds that support
skin integrity and health. Hibiscus syriacus, family Malvaceae, is a plant of
Chinese origin known for its antipyretic, anthelmintic, and antifungal
properties. The aim of this study was to assess the healing and hydration
properties of H. syriacus ethanolic extract (HSEE). We established a cell culture
from Hibiscus syriacus leaves and obtained an ethanol soluble extract from
cultured cells. The properties of the extract were tested by gene expression and
functional analyses on human fibroblast, keratinocytes, and skin explants. HSEE
treatment increased the healing potential of fibroblasts and keratinocytes.
Specifically, HSEE significantly stimulated fibronectin and collagen synthesis by
16 and 60%, respectively, while fibroblasts contractility was enhanced by 30%.
These results were confirmed on skin explants, where HSEE accelerated the wound
healing activity in terms of epithelium formation and fibronectin production.
Moreover, HSEE increased the expression of genes involved in skin hydration and
homeostasis. Specifically, aquaporin 3 and filaggrin genes were enhanced by 20
and 58%, respectively. Our data show that HSEE contains compounds capable of
stimulating expression of biomarkers relevant to skin regeneration and hydration
thereby counteracting molecular pathways leading to skin damage and aging.
PMID- 29333455
TI - Molecular and Cellular Mechanisms of Neuroinflammation.
PMID- 29333454
TI - Virtual Reality Telerehabilitation for Postural Instability in Parkinson's
Disease: A Multicenter, Single-Blind, Randomized, Controlled Trial.
AB - Introduction: Telerehabilitation enables patients to access remote rehabilitation
services for patient-physiotherapist videoconferencing in their own homes. Home
based virtual reality (VR) balance training has been shown to reduce postural
instability in patients with Parkinson's disease (PD). The primary aim was to
compare improvements in postural stability after remotely supervised in-home VR
balance training and in-clinic sensory integration balance training (SIBT).
Methods: In this multicenter study, 76 PD patients (modified Hoehn and Yahr
stages 2.5-3) were randomly assigned to receive either in-home VR
telerehabilitation (n = 38) or in-clinic SIBT (n = 38) in 21 sessions of 50
minutes each, 3 days/week for 7 consecutive weeks. VR telerehabilitation
consisted of graded exergames using the Nintendo Wii Fit system; SIBT included
exercises to improve postural stability. Patients were evaluated before
treatment, after treatment, and at 1-month follow-up. Results: Analysis revealed
significant between-group differences in improvement on the Berg Balance Scale
for the VR telerehabilitation group (p = 0.04) and significant Time * Group
interactions in the Dynamic Gait Index (p = 0.04) for the in-clinic group. Both
groups showed differences in all outcome measures over time, except for fall
frequency. Cost comparison yielded between-group differences in treatment and
equipment costs. Conclusions: VR is a feasible alternative to in-clinic SIBT for
reducing postural instability in PD patients having a caregiver.
PMID- 29333457
TI - Heterologous Secretory Expression and Characterization of Dimerized Bone
Morphogenetic Protein 2 in Bacillus subtilis.
AB - Recombinant human Bone Morphogenetic Protein 2 (rhBMP2) has important
applications in the spine fusion and ortho/maxillofacial surgeries. Here we first
report the secretory expression of biological active dimerized rhBMP2 from
Bacillus subtilis system. The mature domain of BMP2 gene was amplified from
pTz57R/BMP2 plasmid. By using pHT43 expression vector two constructs, pHT43-BMP2
M (single BMP2 gene) and pHT43-BMP2-D (two BMP2 genes coupled with a linker to
produce a dimer), were designed. After primary cloning (DH5alpha strain) and
sequence analysis, constructs were transformed into Bacillus subtilis for
secretory expression. Expression conditions like media (2xYT) and temperature (30
degrees C) were optimized. Maximum 35% and 25% secretory expression of monomer
(~13 kDa) and dimer (~25 kDa), respectively, were observed on SDS-PAGE in SCK6
strain. The expression and dimeric nature of rhBMP2 were confirmed by western
blot and native PAGE analysis. For rhBMP2 purification, 200 ml culture
supernatant was freeze dried to 10 ml and dialyzed (Tris-Cl, pH 8.5) and Fast
Protein Liquid Chromatography (6 ml, Resource Q column) was performed. The rhBMP2
monomer and dimer were eluted at 0.9 M and 0.6 M NaCl, respectively. The alkaline
phosphatase assay of rhBMP2 (0, 50, 100, 200, and 400 ng/ml) was analyzed on
C2C12 cells and maximum 200 ng/ml activity was observed in dose dependent manner.
PMID- 29333456
TI - Protective Effects of Garlic-Derived S-Allylmercaptocysteine on IL-1beta
Stimulated Chondrocytes by Regulation of MMPs/TIMP-1 Ratio and Type II Collagen
Expression via Suppression of NF-kappaB Pathway.
AB - Background: Garlic-derived S-allylmercaptocysteine (SAMC) has widely been used in
many disease therapies. However, the potential effects and mechanism of SAMC on
IL-1beta-stimulated chondrocytes are unclear. Methods: Chondrocytes were
isolated, and 5 ng/mL of IL-1beta was added to mimic the in vitro osteoarthritis
(OA) model. SAMC (20 and 60 MUM) was used for the treatment in OA model. Cell
viability was assessed by MTT method. Western blotting, Quantitative RT-PCR, and
ELISA were performed to evaluate the mechanisms in SAMC treated OA model.
Results: Following 48 h of IL-1beta exposure, SAMC exhibited protection effect on
IL-1beta-injured chondrocyte viability. Type II collagen was elevated with
reduced degradation products, as a consequence of altered MMPs/TIMP-1 ratio after
SAMC treatment in IL-1beta-treated chondrocytes. The protein and mRNA level of
TNF-alpha in cellular supernatant and cells were downregulated in a dose
dependent manner. Besides, IkappaBalpha in cytoplasmic fraction was increased,
while p65 level in nuclear fraction was decreased after SAMC treatment in OA.
Conclusions: This study showed that SAMC may play a protective role in IL-1beta
induced osteoarthritis (OA) model. This effect may be through inhibiting the NF
kappaB signaling pathway, therefore altering the MMPs/TIMP-1 ratio change which
induced type II collagen destruction and decreasing inflammatory cytokine
secretion such as TNF-alpha.
PMID- 29333459
TI - Assessment of Insulin Injection Practice among Diabetes Patients in a Tertiary
Healthcare Centre in Nepal: A Preliminary Study.
AB - Introduction: Proper insulin injection practice is essential for better diabetic
control. This study aims to assess the insulin injection practice of patients
with diabetes. Materials and Methods: A cross-sectional study was conducted at
Chitwan Medical College Teaching Hospital, Bharatpur, Nepal, from February 2017
to May 2017. Patients injecting insulin through insulin pens (n = 43) for a
minimum of 4 weeks were consecutively recruited. Patients' baseline
characteristics, current insulin injection technique, insulin transportation
practice, complications of insulin injection, disposal practice of used needle,
and acceptability of insulin were recorded. Descriptive statistics were performed
using IBM-SPSS 20.0. Results: The insulin injection technique of patients and
their relatives was inadequate. The majority of patients and their relatives (25,
58.1%) mentioned that they transport their insulin cartridge without maintaining
cold chain. Thirteen patients (30.2%, n = 43) reported complications of insulin
injection and the most common complication among those patients was bruising (10,
76.9%, n = 13). Almost all patients disposed the used needle improperly, and the
common method was disposing the needle in a dustbin and then transferring to
municipal waste disposal vehicle. Insulin was accepted by just 16 (37.2%)
patients. Conclusion: There was a significant gap between the insulin delivery
recommendation through insulin pen and current insulin injection practice.
PMID- 29333458
TI - SOX6 Downregulation Induces gamma-Globin in Human beta-Thalassemia Major
Erythroid Cells.
AB - Background: Fetal hemoglobin (HbF; alpha2gamma2) is a potent genetic modifier of
the severity of beta-thalassemia and sickle cell anemia. Differences in the
levels of HbF that persist into adulthood affect the severity of sickle cell
disease and the beta-thalassemia syndromes. Sry type HMG box (SOX6) is a potent
silencer of HbF. Here, we reactivated gamma-globin expression by downregulating
SOX6 to alleviate anemia in the beta-thalassemia patients. Methods: SOX6 was
downregulated by lentiviral RNAi (RNA interference) in K562 cell line and an in
vitro culture model of human erythropoiesis in which erythroblasts are derived
from the normal donor mononuclear cells (MNC) or beta-thalassemia major MNC. The
expression of gamma-globin was analyzed by qPCR (quantitative real-time PCR) and
WB (western blot). Results: Our data showed that downregulation of SOX6 induces
gamma-globin production in K562 cell line and human erythrocytes from normal
donors and beta-thalassemia major donors, without altering erythroid maturation.
Conclusions: This is the first report on gamma-globin induction by downregulation
of SOX6 in human erythroblasts derived from beta-thalassemia major.
PMID- 29333461
TI - Extracorporeal Shock Wave Therapy for Coronary Artery Disease: Relationship of
Symptom Amelioration and Ischemia Improvement.
AB - Objectives: The current management of coronary artery disease (CAD) relies on
three major therapeutic options, namely medication, percutaneous coronary
intervention (PCI), and coronary artery bypass grafting (CABG). However, severe
CAD that is not indicated for PCI or CABG still bears a poor prognosis due to the
lack of effective treatments. In 2006, extracorporeal cardiac shock wave (SW)
therapy reported on human for the first time. This treatment resulted in better
myocardial perfusion as evaluated by dipyridamole stress thallium scintigraphy,
angina symptoms, and exercise tolerance. The aim of the present study was to
investigate: myocardial perfusion images and evaluate the relationship between
the ischemia improvement and symptom amelioration by SW therapy. Methods: We
treated ten patients (i.e., nine males and one female) with cardiac SW therapy
who had CAD but not indicated for PCI or CABG and aged 63-89 years old. After the
SW therapy, all patients were followed up for three months to evaluate any
amelioration of the myocardial ischemia based on symptoms, adenosine stress
thallium scintigraphy, transthoracic echocardiography, and blood biochemical
examinations. Results: The changes in various parameters were evaluated before
and after cardiac SW therapy. The cardiac SW therapy resulted in a significant
improvement in the symptoms as evaluated by the Canadian Cardiovascular Society
[CCS] class score (P=0.016) and a tendency to improve in summed stress score
(SSS) (P=0.068). However, no significant improvement was observed in the summed
rest score (SRS), summed difference score (SDS), left ventricular wall motion
score index (LVWMSI), N-terminal pro-brain natriuretic, and troponin I. The
difference of CCS class score (DeltaCCS) was significantly correlated with those
of SSS (DeltaSSS) and SDS (DeltaSDS) (r=0.69, P=0.028 and r=0.70, P=0.025,
respectively). There was no significant correlation between DeltaCCS and other
parameters. Furthermore, no significant difference was observed between the CCS
improved and non-improved groups in terms of the baseline characteristics.
Conclusion: The current study demonstrated the potential efficacy and safety of
Cardiac SW therapy in CAD patients. As the findings indicated, symptom
amelioration was associated with ischemia improvement by extracorporeal shock
wave therapy for the CAD patients.
PMID- 29333462
TI - Assessment of Ultrasound / Radio-guided Occult Lesion Localization in Non
palpable Breast Lesions.
AB - Objectives: Controversy exists about the localization of non-palpable breast
lesions. In many countries, the gold standard for the diagnosis of these lesions
is needle localization due to its accuracy. This study sought to compare the
ultrasound- and radio-guided occult lesion localization (ROLL) as a simple method
with the conventional procedures in terms of their diagnostic power. Methods:
This study was conducted on 94 patients with non-palpable breast lesions detected
by ultrasonography and localized by the combination of ultrasonography and using
radiopharmaceuticals. One to ten hours prior to surgery, 0.1-0.2 ml (equivalent
to 0.5-1 mCi) of Tc-99m-phytate was injected to the lesion under the guidance of
ultrasonography. Then, the lesion was localized using a hand-held gamma probe,
and excision of the lesion was performed according to its radioactivity signal.
Data analysis was performed using SPSS, version 16. Results: Benign and malignant
pathologic results were observed in 77 (81.9%) and 17(18.1%) of the patients,
respectively, and the mean volume of the excised tissue was 26.29+/-27 mm3. 79
patients had a solitary lesion (84%), 55 in the left breast (58.5%) and 39 in
superolateral quadrant (41.5%). The mean size of the lesions was 15.7 mm in
diameter (ranging from 4 to 34 mm). Additionally, there was a need to secondary
surgery in 3 (3.2%) patients and inappropriate localization in 6 (6.4%) patients
(subcutaneous or intra-ductal spread of radiodrug). Conclusion: Combination of
ultrasound- and radio-guided localization methods for localizing non-palpable
breast lesions is a simple and acceptable method for localization with no
significant complications. For radio-drug spread and subsequent excessive excised
tissue volume, subcutaneous and intra-ductal lesions are not suitable indication
for ROLL.
PMID- 29333460
TI - HLA Association with Drug-Induced Adverse Reactions.
AB - Adverse drug reactions (ADRs) remain a common and major problem in healthcare.
Severe cutaneous adverse drug reactions (SCARs), such as Stevens-Johnson syndrome
(SJS)/toxic epidermal necrolysis (TEN) with mortality rate ranges from 10% to
more than 30%, can be life threatening. A number of recent studies demonstrated
that ADRs possess strong genetic predisposition. ADRs induced by several drugs
have been shown to have significant associations with specific alleles of human
leukocyte antigen (HLA) genes. For example, hypersensitivity to abacavir, a drug
used for treating of human immunodeficiency virus (HIV) infection, has been
proposed to be associated with allele 57:01 of HLA-B gene (terms HLA-B*57:01).
The incidences of abacavir hypersensitivity are much higher in Caucasians
compared to other populations due to various allele frequencies in different
ethnic populations. The antithyroid drug- (ATDs- ) induced agranulocytosis are
strongly associated with two alleles: HLA-B*38:02 and HLA-DRB1*08:03. In
addition, HLA-B*15:02 allele was reported to be related to carbamazepine-induced
SJS/TEN, and HLA-B*57:01 in abacavir hypersensitivity and flucloxacillin induced
drug-induced liver injury (DILI). In this review, we summarized the alleles of
HLA genes which have been proposed to have association with ADRs caused by
different drugs.
PMID- 29333463
TI - Characteristics of Smoothing Filters to Achieve the Guideline Recommended
Positron Emission Tomography Image without Harmonization.
AB - Objectives: The aim of this study is to examine the effect of different smoothing
filters on the image quality and SUVmax to achieve the guideline recommended
positron emission tomography (PET) image without harmonization. Methods: We used
a Biograph mCT PET scanner. A National Electrical Manufacturers Association
(NEMA) the International Electrotechnical Commission (IEC) body phantom was
filled with 18F solution with a background activity of 2.65 kBq/mL and a sphere
to-background ratio of 4. PET images obtained with the Biograph mCT PET scanner
were reconstructed using the ordered subsets-expectation maximization (OSEM)
algorithm with time-of-flight (TOF) models (iteration, 2; subset, 21); smoothing
filters including the Gaussian, Butterworth, Hamming, Hann, Parzen, and Shepp
Logan filters with various full width at half maximum (FWHM) values (1-15 mm)
were applied. The image quality was physically assessed according to the percent
contrast (QH,10), background variability (N10), standardized uptake value (SUV),
and recovery coefficient (RC). The results were compared with the guideline
recommended range proposed by the Japanese Society of Nuclear Medicine and the
Japanese Society of Nuclear Medicine Technology. The PET digital phantom was
developed from the digital reference object (DRO) of the NEMA IEC body phantom
smoothed using a Gaussian filter with a 10-mm FWHM and defined as the reference
image. The difference in the SUV between the PET image and the reference image
was evaluated according to the root mean squared error (RMSE). Results: The FWHMs
of the Gaussian, Butterworth, Hamming, Hann, Parzen, and Shepp-Logan filters that
satisfied the image quality of the FDG-PET/CT standardization guideline criteria
were 8-12 mm, 9-11 mm, 9-13 mm, 10-13 mm, 9-11 mm, and 12-15 mm, respectively.
The FWHMs of the Gaussian, Butterworth, Hamming, Hann, Parzen, and Shepp-Logan
filters that provided the smallest RMSE between the PET images and the 3D digital
phantom were 7 mm, 8 mm, 8 mm, 8 mm, 7 mm, and 11 mm, respectively. Conclusion:
The suitable FWHM for image quality or SUVmax depends on the type of smoothing
filter that is applied.
PMID- 29333464
TI - Comparison of TOF-PET and Bremsstrahlung SPECT Images of Yttrium-90: A Monte
Carlo Simulation Study.
AB - Objectives: Yttrium-90 (90Y) is a beta particle nuclide used in targeted
radionuclide therapy which is available to both single-photon emission computed
tomography (SPECT) and time-of-flight (TOF) positron emission tomography (PET)
imaging. The purpose of this study was to assess the image quality of PET and
Bremsstrahlung SPECT by simulating PET and SPECT images of 90Y using Monte Carlo
simulation codes under the same conditions and to compare them. Methods: In-house
Monte Carlo codes, MCEP-PET and MCEP-SPECT, were employed to simulate images. The
phantom was a torso-shaped phantom containing six hot spheres of various sizes.
The background concentrations of 90Y were set to 50, 100, 150, and 200 kBq/mL,
and the concentrations of the hot spheres were 10, 20, and 40 times of those of
the background concentrations. The acquisition time was set to 30 min, and the
simulated sinogram data were reconstructed using the ordered subset expectation
maximization method. The contrast recovery coefficient (CRC) and contrast-to
noise ratio (CNR) were employed to evaluate the image qualities. Results: The CRC
values of SPECT images were less than 40%, while those of PET images were more
than 40% when the hot sphere was larger than 20 mm in diameter. The CNR values of
PET images of hot spheres of diameter smaller than 20 mm were larger than those
of SPECT images. The CNR values mostly exceeded 4, which is a criterion to
evaluate the discernibility of hot areas. In the case of SPECT, hot spheres of
diameter smaller than 20 mm were not discernable. On the contrary, the CNR values
of PET images decreased to the level of SPECT, in the case of low concentration.
Conclusion: In almost all the cases examined in this investigation, the
quantitative indexes of TOF-PET 90Y images were better than those of
Bremsstrahlung SPECT images. However, the superiority of PET image became
critical in the case of low activity concentrations.
PMID- 29333465
TI - In vivo Exposure Effects of 99mTc-methoxyisobutylisonitrile on the FDXR and XPA
Genes Expression in Human Peripheral Blood Lymphocytes.
AB - Objectives: In recent years, the application of radiopharmaceuticals in nuclear
medicine has increased substantially. Following the diagnostic procedures
performed in nuclear medicine departments, such as myocardial perfusion imaging,
patients generally receive considerable doses of radiation. Normally, radiation
induced DNA damages are expected following exposure to a low-dose ionizing
radiation. In order to detect molecular changes, high-sensitivity techniques must
be utilized. The aim of this study was to assess the effect of a low-dose (below
10 mSv) gamma ray on gene expression using quantitative real-time polymerase
chain reaction (qRT-PCR). Methods: Blood samples were obtained from 20 volunteer
patients who underwent myocardial perfusion imaging. They were given various
doses of Technetium-99m methoxyisobutylisonitrile (99mTc-MIBI). After that,
peripheral blood mononuclear cells (PBMNs) were derived, and then total RNA was
extracted and reverse-transcribed to cDNA. Finally, the expression levels of
xeroderma pigmentosum complementation group-A (XPA) and ferredoxin reductase
(FDXR) genes were determinded through qRT-PCR technique using SYBR Green.
Results: XPA and FDXR expression levels were obtained following a very low-dose
ionizing radiation. A significant up-regulation of both genes was observed, and
the gene expression level of each individual patient was different. If
differences in the administered activity and radiosensitivity are taken into
account, the observed differences could be justified. Furthermore, gender and age
did not play a significant role in the expression levels of the genes under
study. Conclusion: The up-regulation of FDXR after irradiation revealed the high
sensitivity level of this gene; therefore, it could be used as an appropriate
biomarker for biological dosimetry. On the other hand, the up-regulation of XPA
is an indication of DNA repair following radiation exposure. According to linear
no-threshold model (LNT) and the results obtained from this study, a very low
dose of ionizing radiation could bring about adverse biological effects at
molecular level in the irradiated person.
PMID- 29333466
TI - Evaluation of the Possible Utilization of 68Ga-DOTATOC in Diagnosis of
Adenocarcinoma Breast Cancer.
AB - Objectives: Studies have indicated advantageous properties of [DOTA-DPhe1, Tyr3]
octreotide (DOTATOC) in tumor models and labeling with gallium. Breast cancer is
the second leading cause of cancer mortality in women, and most of these cancers
are often an adenocarcinoma. Due to the importance of target to non-target ratios
in the efficacy of diagnosis, the pharmacokinetic of 68Ga-DOTATOC in an
adenocarcinoma breast cancer animal model was studied in this research, and the
optimized time for imaging was determined. Methods: 68Ga was obtained from
68Ge/68Ga generator. The complex was prepared at optimized conditions.
Radiochemical purity of the complex was checked using both HPLC and ITLC methods.
Biodistribution of the complex was studied in BALB/c mice bearing adenocarcinoma
breast cancer. Also, PET/CT imaging was performed up to 120 min post injection.
Results: The complex was produced with radiochemical purity of greater than 98%
and specific activity of about 40 GBq/mM at optimized conditions. Biodistribution
of the complex was studied in BALB/c mice bearing adenocarcinoma breast cancer
indicated fast blood clearance and significant uptake in the tumor. Significant
tumor: blood and tumor:muscle uptake ratios were observed even at early times
post-injection. PET/CT images were also confirmed the considerable accumulation
of the tracer in the tumor. Conclusion: Generally, the results proved the
possible application of the radiolabelled complex for the detection of the
adenocarcinoma breast cancer and according to the pharmacokenitic data, the
suitable time for imaging was determined as at least 30 min after injection.
PMID- 29333467
TI - A Simple Non-invasive I-123-IMP Autoradiography Method Developed by Modifying the
Simple Non-invasive I-123-IMP Microsphere Method.
AB - Objectives: We developed a simple non-invasive I-123-N-isopropyl-p
iodoamphetamine (123I-IMP) quantification method by analyzing chest RI
angiography and single photon emission computed tomography (SPECT) images based
on the microsphere model (SIMS method). Theoretically, the SIMS method could be
changed to the simple non-invasive ARG (SIARG) method by modifying the integrated
washout ratio (WR) to one-point WR. If the regional cerebral blood flow (rCBF)
values derived from the SIARG and ARG methods correlate well, the facilities
employing the ARG method can easily switch to the SIARG method. The purpose of
this study was to develop the SIARG method by modifying the SIMS method, and to
confirm the feasibility of this method. Methods: The correlation between the
input counts of the SIARG method and the blood counts was determined by linear
regression analysis. The rCBF values determined by the SIARG method were compared
with the values obtained with the ARG and SIMS methods. Results: There was a good
linear correlation between the SIARG counts and the arterial blood counts
obtained by the ARG method (r=0.85, P<0.001, n=29). The rCBF values obtained by
the ARG and SIARG methods (n=29, 696 ROIs) correlated well (y=1.01x - 3.6,
r=0.85, P<0.001). Similarly, the rCBF values obtained by the SIARG and SIMS
methods (n=29, 696 ROIs) correlated well (y=0.98x - 15.2, r=0.90, P<0.001). rCBF
values obtained by the SIARG method were almost the same as the values obtained
by the ARG method, and values of the SIMS method were 15 ml/100g/min higher that
of those obtained by the SIARG method. Conclusion: The rCBF values obtained by
the ARG, SIARG, and SIMS methods correlated very well. Therefore, the SIARG
method is potentially useful for examinations in routine clinical practice.
PMID- 29333468
TI - Extraosseous Accumulation of Technetium-99m-Methyl Diphosphonate (99mTc-MDP) in a
Child with ALL: A Case Report.
AB - Extraosseous accumulation of technetium-99m-methyl diphosphonate (99mTc-MDP) on
bone scan is not common. This phenomenon is often attributed to abnormality of
calcium metabolism and has been reported in a variety of conditions including
metabolic diseases and malignancies. A five years old boy is presented here, who
was admitted to the pediatric emergency suffering from fatigue, respiratory
symptoms, weight loss, intermittent fevers, anorexia, nausea and vomiting, edema
of legs and abdominal distension for one month. The initial laboratory analysis
revealed hypercalcemia. The patient was referred for whole body bone scan with
suspicion of malignancy and bone metastasis. The bone scan revealed highly
increased radiotracer uptake in both lungs in the perfusion and blood pool
phases. Delayed images also showed increased activity in lungs and gastric wall.
The skeleton was not seen clearly. Bone marrow aspiration was done and
established the diagnosis of ALL. The patient deceased due to respiratory failure
20 days later. Diffuse lung uptake in this patient was consistent with
respiratory failure and poor prognosis. It is reported that bone scan may be
useful for assessment of the extent of metastatic calcification and may establish
suitable management to prevent organ failure.
PMID- 29333469
TI - Utility of F-18 FDG PET/CT for Detection of Bone Marrow Metastases in Prostate
Cancer Patients Treated with Radium-223.
AB - A 76-year-old man with symptomatic bone metastases from castration-resistant
prostate cancer underwent Radium-223-dichloride (Ra-223) therapy. Before Ra-223
therapy, he had normal peripheral blood cell counts. Ra-223 therapy relieved his
shoulder and low back pain. The elevation of the serum prostate-specific antigen
(PSA), doubling every month during Ra-223 therapy, suggested a PSA flare or
relapse. Some lesions showed decrease and some lesions showed increase on Tc-99m
hydroxymethylene diphosphonate bone scintigraphy at two weeks after the third
injection of Ra-223 therapy. Ra-223 therapy was discontinued due to
thrombocytopenia that was getting worse rapidly. After treatment discontinuation,
namely four weeks after the third injection of Ra-223, F-18 fluorodeoxyglucose
(FDG) Positron Emission Tomography (PET)/CT and a biopsy were performed to
evaluate for metastases, and bone marrow metastases were found. Ra-223 was
effective for osteoblastic lesions, but not for bone marrow metastases. FDG
PET/CT, but not a Tc-99m based bone scan, detected diffuse bone marrow
involvement by cancer. This case report is the first to clarify the utility of
FDG PET for the detection of bone marrow metastases confirmed by pathological
examination in Ra-223 therapy for progressive castration-resistant prostate
cancer.
PMID- 29333470
TI - History and Perspectives of Nuclear Medicine in Myanmar.
AB - Nuclear Medicine was established in Myanmar in 1963 by Dr Soe Myint and
International Atomic Energy expert Dr R. Hochel at Yangon General Hospital.
Nuclear medicine diagnostic and therapeutic services started with Probe
Scintillation Detector Systems and rectilinear scanner. In the early stage, many
Nuclear Medicine specialists from the International Atomic Energy Agency (IAEA)
spent some time in Myanmar and made significant contributions to the development
of Nuclear Medicine in our country. The department participated in various IAEA
technical cooperation projects and regional cooperation projects. By the late
1990s, new centers were established in Mandalay, Naypyidaw, and North Okkalapa
Teaching Hospital of University of Medicine 11, Yangon. The training program
related to Nuclear Medicine includes a postgraduate master's degree (three years)
at the University of Medicine. Currently, all centers are equipped with SPECT,
SPECT-CT, PET-CT, and cyclotron in Yangon General Hospital. Up until now, the
International Atomic Energy Agency has been playing a crucial role in the growth
and development of Nuclear Medicine in Myanmar. Our vision is to provide a wide
spectrum of nuclear medicine services at a level compatible with the
international standards to become a Center of Excellence.
PMID- 29333471
TI - Sectional Anatomy Quiz II.
AB - This mage-based series comprises of a quiz pertaining to the identification of
salient and important anatomical structures and landmarks expected to be seen at
a given level on the computed tomography (CT). The representative image is
followed by a series of images showing the examples of different commonly
encountered pathological entities that can be seen at this level in a routine
clinical practice. Readers are encouraged to identify the highlighted anatomical
structures and landmarks in all the images and appreciate the alterations in the
appearance of the normal structures resulting from the presence of a pathology.
It is expected that this series will assist in improving the confidence of the
nuclear physicians in the interpretation of the CT component of the single photon
emission computed tomography (SPECT) and positron emission tomography (PET)
studies.
PMID- 29333472
TI - Black-White Disparities in Breast Cancer Subtype: The Intersection of Socially
Patterned Stress and Genetic Expression.
AB - Hormone receptor negative (HR-) breast cancer subtypes are etiologically distinct
from the more common, less aggressive, and more treatable form of estrogen
receptor positive (ER+) breast cancer. Numerous population-based studies have
found that, in the United States, Black women are 2 to 3 times more likely to
develop HR- breast cancer than White women. Much of the existing research on
racial disparities in breast cancer subtype has focused on identifying
predisposing genetic factors associated with African ancestry. This approach
fails to acknowledge that racial stratification shapes a wide range of
environmental and social exposures over the life course. Human stress genomics
considers the role of individual stress perceptions on gene expression. Yet, the
role of structurally rooted biopsychosocial processes that may be activated by
the social patterning of stressors in an historically unequal society, whether
perceived by individual black women or not, could also impact cellular physiology
and gene expression patterns relevant to HR- breast cancer etiology. Using the
weathering hypothesis as our conceptual framework, we develop a structural
perspective for examining racial disparities in breast cancer subtypes,
integrating important findings from the stress biology, breast cancer
epidemiology, and health disparities literatures. After integrating key findings
from these largely independent literatures, we develop a theoretically and
empirically guided framework for assessing potential multilevel factors relevant
to the development of HR- breast cancer disproportionately among Black women in
the US. We hypothesize that a dynamic interplay among socially patterned
psychosocial stressors, physiological & behavioral responses, and genomic
pathways contribute to the increased risk of HR- breast cancer among Black women.
This work provides a basis for exploring potential alternative pathways linking
the lived experience of race to the risk of HR- breast cancer, and suggests new
avenues for research and public health action.
PMID- 29333474
TI - Saccades in progressive supranuclear palsy - maladapted, irregular, curved, and
slow.
AB - Background and objectives: Slowed and curved rapid eye movements, saccades, are
the well-known features of progressive supranuclear palsy (PSP). We hypothesized
that the saccades in PSP are not only slow and curved, but they are also
irregular and have timing deficits. Methods: We tested this hypothesis in 12
patients with PSP by measuring vertical and horizontal visually guided saccades
using a limbus tracker. Results: Both, horizontal and vertical saccades were slow
and had irregular trajectory and velocity profiles, but deficits were much more
robust in vertical saccades. The irregularity in the saccade velocity was due to
premature interruptions that either completely stopped the eyes, or moved the
eyes at much slower velocity along or in the opposite direction of the ongoing
saccade. The direction of the eyes' trajectory was often changed after the
interruption. We simulated a conductance based single-compartment model of the
burst neurons embedded in local feedback circuit for saccade generation. This
model mimicked anatomical and physiological realism, while allowing the liberty
to selectively change the activation of individual burst neurons or the pause
neurons. The PSP saccades were comparable to the simulations during reduced
activity of the inhibitory and excitatory burst neurons. Conclusion: PSP saccades
are due to the paucity in burst generation at the excitatory and imprecise timing
signal from the inhibitory burst neurons. Premature discharge of the inhibitory
burst neuron further leads to breaks in the saccade trajectory, and maladaptive
superior colliculus activity leading to aberrant saccades changing the intended
trajectory of the ongoing saccade.
PMID- 29333475
TI - Whole-mount Enteroid Proliferation Staining.
AB - Small intestinal organoids, otherwise known as enteroids, have become an
increasingly utilized model for intestinal biology in vitro as they recapitulate
the various epithelial cells within the intestinal crypt (Mahe et al., 2013; Sato
et al., 2009). Assessment of growth dynamics within these cultures is an
important step to understanding how alterations in gene expression, treatment
with protective and toxic agents, and genetic mutations alter properties
essential for crypt growth and survival as well as the stem cell properties of
the individual cells within the crypt. This protocol describes a method of
visualization of proliferating cells within the crypt in three dimensions
(Barrett et al., 2015). Whole-mount proliferation staining of enteroids using EdU
incorporation enables the researcher to view all proliferating cells within the
enteroid as opposed to obtaining growth information in thin slices as would be
seen with embedding and sectioning, ensuring a true representation of
proliferation from the stem cell compartment to the terminally differentiated
cells of the crypt.
PMID- 29333476
TI - In vitro Flow Adhesion Assay for Analyzing Shear-resistant Adhesion of Metastatic
Cancer Cells to Endothelial Cells.
AB - Hematogenous metastasis is a primary cause of mortality from metastatic cancer.
The shear-resistant adhesion of circulating tumor cells to the vascular
endothelial cell surface under blood flow is an essential step in cell
extravasation and further tissue invasion. This is similar to a process exploited
by leukocytes for adhesion to inflamed blood vessels (leukocyte mimicry). The
shear resistant adhesion is mediated by high affinity interactions between
endothelial adhesion molecules and their counter receptor ligand expressed on
circulating cells. Thus, weak interaction results in a rapid detachment of
circulating cells from endothelium. Despite the critical role of vascular
adhesion of cancer cells in hematogenous metastasis, our knowledge regarding this
process has been limited due to the difficulty of mimicking dynamic flow
conditions in vitro. In order to gain better insight into the shear-resistant
adhesion of cancer cells to the endothelium, we developed a protocol for
measuring the shear resistant adhesion of circulating tumor cells to endothelial
cells under physiologic flow conditions by adapting a well established flow
adhesion assay for inflammatory cells. This technique is useful to evaluate 1)
the shear resistant adhesion competency of cancer cells and 2) the endothelial
adhesion molecules necessary to support cancer cell adhesion (Kang et al., 2015).
PMID- 29333477
TI - Notch Ligand Binding Assay Using Flow Cytometry.
AB - Notch signaling is an evolutionary conserved signaling pathway that plays an
indispensable role during development, and in the maintenance of homeostatic
processes, in a wide variety of tissues (Kopan, 2012; Hori et al., 2013). The
multifaceted roles of Notch signaling are stringently regulated at different
levels. One of the most important aspects of regulation is the binding of
different Notch ligands to each Notch receptor (NOTCH1-NOTCH4). Canonical ligands
Delta or Serrate (in Drosophila), and Delta-like (DLL1 and DLL4) or Jagged (JAG1
and JAG2) (in mammals), are transmembrane glycoproteins. Ligands expressed on one
cell bind to Notch receptors on an adjacent cell to induce Notch signaling.
Glycosylation of Notch receptor extracellular domain by O-fucose and O-GlcNAc
glycans is well established as critical regulators for Notch signaling strength
(Stanley and Okajima, 2010; Haltom and Jafar-Nejad, 2015; Sawaguchi et al.,
2017). In order to characterize Notch ligand binding to Notch receptors in
isolated cells, we utilize Notch ligand extracellular domains tagged at the C
terminus by a human Fc domain, and determine binding of fluorescent anti-Fc
antibody by flow cytometry.
PMID- 29333473
TI - Charge migration and charge transfer in molecular systems.
AB - The transfer of charge at the molecular level plays a fundamental role in many
areas of chemistry, physics, biology and materials science. Today, more than 60
years after the seminal work of R. A. Marcus, charge transfer is still a very
active field of research. An important recent impetus comes from the ability to
resolve ever faster temporal events, down to the attosecond time scale. Such a
high temporal resolution now offers the possibility to unravel the most
elementary quantum dynamics of both electrons and nuclei that participate in the
complex process of charge transfer. This review covers recent research that
addresses the following questions. Can we reconstruct the migration of charge
across a molecule on the atomic length and electronic time scales? Can we use
strong laser fields to control charge migration? Can we temporally resolve and
understand intramolecular charge transfer in dissociative ionization of small
molecules, in transition-metal complexes and in conjugated polymers? Can we
tailor molecular systems towards specific charge-transfer processes? What are the
time scales of the elementary steps of charge transfer in liquids and
nanoparticles? Important new insights into each of these topics, obtained from
state-of-the-art ultrafast spectroscopy and/or theoretical methods, are
summarized in this review.
PMID- 29333478
TI - A General Method for Intracellular Protein Delivery through 'E-tag' Protein
Engineering and Arginine Functionalized Gold Nanoparticles.
AB - In this protocol, we describe a method for direct cytosolic protein delivery that
avoids endosomal entrapment of the delivered proteins. We achieved this by
tagging the desired protein with an oligo glutamic acid tag (E-tag), and
subsequently using carrier gold nanoparticles to deliver these E-tagged proteins.
When E-tagged proteins and nanoparticles were mixed, they formed nanoassemblies,
which got fused to cell membrane upon incubation and directly released the E
tagged protein into cell cytosol. We used this method to deliver a wide variety
of proteins with different sizes, charges, and functions in various cell lines
(Mout et al., 2017). To use this protocol, the first step is to generate the
required materials (gold nanoparticles, recombinant E-tagged proteins).
Laboratory-synthesis of gold nanoparticles has been previously described (Yang et
al., 2011). Desired E-tagged proteins can be cloned from the corresponding genes,
and expressed and purified using standard laboratory procedures. We will use E
tagged green fluorescent protein (GFP) as a reference protein here. Users can
simply insert an E-tag into their protein of interest, at either terminus. To
achieve maximum delivery efficiency, we suggest users testing different length of
E-tags. For example, we inserted E = 0 to 20 (E0 means no E-tag insertion, and
E20 means 20 glutamic acids insertion in a row) to most of the proteins we
tested, and screened for optimal E-tagged length for highest delivery efficiency.
E10-tagged proteins gave us the highest delivery efficiency for most of the
proteins (except for Cas9, where E20 tag showed highest delivery efficiency).
Once these materials are ready, it takes about ~10 min to make the E-tagged
protein and nanoparticle nanoassemblies, which are immediately used for delivery.
Complete delivery (~100% for GFP-E10) is achieved in less than 3 h.
PMID- 29333479
TI - Oral Microbiome Characterization in Murine Models.
AB - The oral microbiome has been implicated as a trigger for immune responsiveness in
the oral cavity, particularly in the setting of the inflammatory disease
periodontitis. The protocol presented here is aimed at characterizing the oral
microbiome in murine models at steady state and during perturbations of immunity
or physiology. Herein, we describe murine oral microbiome sampling procedures,
processing of low biomass samples and subsequent microbiome characterization
based on 16S rRNA gene sequencing.
PMID- 29333480
TI - GPU-based Branchless Distance-Driven Projection and Backprojection.
AB - Projection and backprojection operations are essential in a variety of image
reconstruction and physical correction algorithms in CT. The distance-driven (DD)
projection and backprojection are widely used for their highly sequential memory
access pattern and low arithmetic cost. However, a typical DD implementation has
an inner loop that adjusts the calculation depending on the relative position
between voxel and detector cell boundaries. The irregularity of the branch
behavior makes it inefficient to be implemented on massively parallel computing
devices such as graphics processing units (GPUs). Such irregular branch behaviors
can be eliminated by factorizing the DD operation as three branchless steps:
integration, linear interpolation, and differentiation, all of which are highly
amenable to massive vectorization. In this paper, we implement and evaluate a
highly parallel branchless DD algorithm for 3D cone beam CT. The algorithm
utilizes the texture memory and hardware interpolation on GPUs to achieve fast
computational speed. The developed branchless DD algorithm achieved 137-fold
speedup for forward projection and 188-fold speedup for backprojection relative
to a single-thread CPU implementation. Compared with a state-of-the-art 32-thread
CPU implementation, the proposed branchless DD achieved 8-fold acceleration for
forward projection and 10-fold acceleration for backprojection. GPU based
branchless DD method was evaluated by iterative reconstruction algorithms with
both simulation and real datasets. It obtained visually identical images as the
CPU reference algorithm.
PMID- 29333481
TI - Theta sequences of grid cell populations can provide a movement-direction signal.
AB - It has been proposed that path integration in mammals is performed by the
convergence of internally generated speed and directional inputs onto grid cells.
Although this hypothesis has been supported by the discovery that head direction,
speed, and grid cells are intermixed within entorhinal cortex and by the recent
finding that head-direction inputs are necessary for grid firing, many details on
how grid cells are generated have remained elusive. For example, analysis of
recording data suggests that substituting head direction for movement direction
accrues errors that preclude the formation of grid patterns. To address this
discrepancy, we propose that the organization of grid networks makes it plausible
that movement-direction signals are an output from grid cells and that temporally
precise grid cell sequences provide a robust directional signal to other spatial
and directional cell types.
PMID- 29333482
TI - Flexibility in the face of fear: Hippocampal-prefrontal regulation of fear and
avoidance.
AB - Generating appropriate defensive behaviors in the face of threat is essential to
survival. Although many of these behaviors are 'hard-wired', they are also
flexible. For example, Pavlovian fear conditioning generates learned defensive
responses, such as conditioned freezing, that can be suppressed through
extinction. The expression of extinguished responses is highly context-dependent,
allowing animals to engage behavioral responses appropriate to the contexts in
which threats are encountered. Likewise, animals and humans will avoid noxious
outcomes if given the opportunity. In instrumental avoidance learning, for
example, animals overcome conditioned defensive responses, including freezing, in
order to actively avoid aversive stimuli. Recent work has greatly advanced
understanding of the neural basis of these phenomena and has revealed common
circuits involved in the regulation of fear. Specifically, the hippocampus and
medial prefrontal cortex play pivotal roles in gating fear reactions and
instrumental actions, mediated by the amygdala and nucleus accumbens,
respectively. Because an inability to adaptively regulate fear and defensive
behavior is a central component of many anxiety disorders, the brain circuits
that promote flexible responses to threat are of great clinical significance.
PMID- 29333483
TI - How heart rate variability affects emotion regulation brain networks.
AB - Individuals with high heart rate variability tend to have better emotional well
being than those with low heart rate variability, but the mechanisms of this
association are not yet clear. In this paper, we propose the novel hypothesis
that by inducing oscillatory activity in the brain, high amplitude oscillations
in heart rate enhance functional connectivity in brain networks associated with
emotion regulation. Recent studies using daily biofeedback sessions to increase
the amplitude of heart rate oscillations suggest that high amplitude
physiological oscillations have a causal impact on emotional well-being. Because
blood flow timing helps determine brain network structure and function, slow
oscillations in heart rate have the potential to strengthen brain network
dynamics, especially in medial prefrontal regulatory regions that are
particularly sensitive to physiological oscillations.
PMID- 29333485
TI - Study of Incidence of Gross Urogenital Lesions and Abnormalities on Does
Slaughtered at Nyagatare Slaughterhouse, Eastern Province, Rwanda.
AB - Reproductive and urinary tract abnormalities are a cause of infertility,
reproductive inefficiency, and economic losses in goats. The aim of this study
was to investigate the occurrence and nature of reproductive and urinary tract
abnormalities encountered in female goats slaughtered at Nyagatare abattoir in
the Eastern Province of Rwanda. Reproductive and urinary organs from 369 female
goat carcasses were opened by incision and then given a thorough macroscopic
examination by visually inspecting and palpating for evidence of abnormalities.
The results showed that there was an overall occurrence of 7.8% reproductive
organ/tract abnormalities and 10.6% urinary organ/tract abnormalities. Ovarian
hypoplasia was the reproductive abnormality with the highest overall occurrence
(32.3%) and renal calculi were the urinary organ abnormality with the highest
occurrence (38.1%). 95.2% of the reproductive organ/tract abnormalities observed
usually result in infertility and 91.3% of the urinary organ/tract abnormalities
observed result in economic losses through condemnation of kidneys at slaughter.
The high incidence of the observed urinary organ/tract abnormalities represents a
potential public health challenge. There was no significant difference in the
occurrence of reproductive organ/tract abnormalities according to breed (p >
0.05, n = 31). There was also no significant difference in the occurrence of
urinary organ abnormalities according to breed (p > 0.05, n = 42).
PMID- 29333486
TI - Ethical Considerations When Delivering Behavior Analytic Services for Problem
Behavior via Telehealth.
AB - Delivery of healthcare services via telehealth has been growing in popularity,
and work completed by behavior analytic researchers and practitioners have
supported this trend. Behavior analysts at the University of Iowa Children's
Hospital (UICH) developed a telehealth model of service delivery to build upon
their already established in-clinic and in-home services. Results from their
telehealth studies showed positive effects. Social functions were identified for
most children, and problem behavior decreased by an average of 94.14%.
Additionally, parent satisfaction was quite high, suggesting this mode of service
delivery was acceptable to caregivers. Given the increasing empirical support for
providing behavior analytic services via telehealth, careful consideration needs
to be given to the numerous ethical issues involved in telehealth service
delivery. The current article describes the telehealth service delivery model
developed at UICH as well as the ethical issues considered at different points
when delivering these telehealth services. Following these ethical
considerations, implications for future research and clinical practice are
discussed.
PMID- 29333484
TI - Approaching the third decade of paediatric palliative oncology investigation:
historical progress and future directions.
AB - Paediatric palliative care (PPC) endeavours to alleviate the suffering and
improve the quality of life of children with serious illnesses and their
families. In the past two decades since WHO defined PPC and called for its
inclusion in paediatric oncology care, rigorous investigation has provided
important insights. For example, the first decade of research focused on end-of
life experiences of the child and the family, underscoring the high prevalence of
symptom burden, the barriers to parent-provider concordance with regards to
prognosis, as well as the need for bereavement supports. The second decade
expanded PPC oncology investigation to include the entire cancer continuum and
the voices of patients. Other studies identified the need for support of parents,
siblings, and racial and ethnic minority groups. Promising interventions designed
to improve outcomes were tested in randomised clinical trials. Future research
will build on these findings and pose novel questions about how to continue to
reduce the burdens of paediatric cancer.
PMID- 29333487
TI - Activation of the Medial Prefrontal Cortex Reverses Cognitive and Respiratory
Symptoms in a Mouse Model of Rett Syndrome.
AB - Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by loss-of
function mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2; Amir
et al., 1999), a transcriptional regulatory protein (Klose et al., 2005). Mouse
models of RTT (Mecp2 mutants) exhibit excitatory hypoconnectivity in the medial
prefrontal cortex (mPFC; Sceniak et al., 2015), a region critical for functions
that are abnormal in RTT patients, ranging from learning and memory to regulation
of visceral homeostasis (Riga et al., 2014). The present study was designed to
test the hypothesis that increasing the activity of mPFC pyramidal neurons in
heterozygous female Mecp2 mutants (Hets) would ameliorate RTT-like symptoms,
including deficits in respiratory control and long-term retrieval of auditory
conditioned fear. Selective activation of mPFC pyramidal neurons in adult animals
was achieved by bilateral infection with an AAV8 vector expressing excitatory
hm3D(Gq) DREADD (Designer Receptors Exclusively Activated by Designer Drugs)
(Armbruster et al., 2007) under the control of the CamKIIa promoter. DREADD
activation in Mecp2 Hets completely restored long-term retrieval of auditory
conditioned fear, eliminated respiratory apneas, and reduced respiratory
frequency variability to wild-type (Wt) levels. Reversal of respiratory symptoms
following mPFC activation was associated with normalization of Fos protein
levels, a marker of neuronal activity, in a subset of brainstem respiratory
neurons. Thus, despite reduced levels of MeCP2 and severe neurological deficits,
mPFC circuits in Het mice are sufficiently intact to generate normal behavioral
output when pyramidal cell activity is increased. These findings highlight the
contribution of mPFC hypofunction to the pathophysiology of RTT and raise the
possibility that selective activation of cortical regions such as the mPFC could
provide therapeutic benefit to RTT patients.
PMID- 29333488
TI - Dopamine Development in the Mouse Orbital Prefrontal Cortex Is Protracted and
Sensitive to Amphetamine in Adolescence.
AB - The prefrontal cortex (PFC) is divided into subregions, including the medial and
orbital prefrontal cortices. Dopamine connectivity in the medial PFC (mPFC)
continues to be established throughout adolescence as the result of the
continuous growth of axons that innervated the nucleus accumbens (NAcc) prior to
adolescence. During this period, dopamine axons remain vulnerable to
environmental influences, such as drugs used recreationally by humans. The
developmental trajectory of the orbital prefrontal dopamine innervation remains
almost completely unstudied. Nonetheless, the orbital PFC (oPFC) is critical for
some of the most complex functions of the PFC and is disrupted by drugs of abuse,
both in adolescent humans and rodents. Here, we use quantitative neuroanatomy,
axon-initiated viral-vector recombination, and pharmacology in mice to determine
the spatiotemporal development of the dopamine innervation to the oPFC and its
vulnerability to amphetamine in adolescence. We find that dopamine innervation to
the oPFC also continues to increase during adolescence and that this increase is
due to the growth of new dopamine axons to this region. Furthermore, amphetamine
in adolescence dramatically reduces the number of presynaptic sites on oPFC
dopamine axons. In contrast, dopamine innervation to the piriform cortex is not
protracted across adolescence and is not impacted by amphetamine exposure during
adolescence, indicating that dopamine development during adolescence is a
uniquely prefrontal phenomenon. This renders these fibers, and the PFC in
general, particularly vulnerable to environmental risk factors during
adolescence, such as recreational drug use.
PMID- 29333489
TI - Degradable acetalated dextran microparticles for tunable release of an engineered
hepatocyte growth factor fragment.
AB - Injectable biomaterials are promising as new therapies to treat myocardial
infarction (MI). One useful property of biomaterials is the ability to protect
and sustain release of therapeutic payloads. In order to create a platform for
optimizing the release rate of cardioprotective molecules we utilized the tunable
degradation of acetalated dextran (AcDex). We created microparticles with three
distinct degradation profiles and showed that the consequent protein release
profiles could be modulated within the infarcted heart. This enabled us to
determine how delivery rate impacted the efficacy of a model therapeutic, an
engineered hepatocyte growth factor fragment (HGF-f). Our results showed that the
cardioprotective efficacy of HGF-f was optimal when delivered over three days
post-intramyocardial injection, yielding the largest arterioles, fewest apoptotic
cardiomyocytes bordering the infarct and the smallest infarcts compared to empty
particle treatment four weeks after injection. This work demonstrates the
potential of using AcDex particles as a delivery platform to optimize the time
frame for delivering therapeutic proteins to the heart.
PMID- 29333490
TI - Inhibition of Bacterial Adhesion on Nanotextured Stainless Steel 316L by
Electrochemical Etching.
AB - Bacterial adhesion to stainless steel 316L (SS316L), which is an alloy typically
used in many medical devices and food processing equipment, can cause serious
infections along with substantial healthcare costs. This work demonstrates that
nanotextured SS316L surfaces produced by electrochemical etching effectively
inhibit bacterial adhesion of both Gram-negative Escherichia coli and Gram
positive Staphylococcus aureus, but exhibit cytocompatibility and no toxicity
toward mammalian cells in vitro. Additionally, the electrochemical surface
modification on SS316L results in formation of superior passive layer at the
surface, improving corrosion resistance. The nanotextured SS316L offers
significant potential for medical applications based on the surface structure
induced reduction of bacterial adhesion without use of antibiotic or chemical
modifications while providing cytocompatibility and corrosion resistance in
physiological conditions.
PMID- 29333491
TI - Multifunctional Bioreactor System for Human Intestine Tissues.
AB - The three-dimensional (3D) cultivation of intestinal cells and tissues in dynamic
bioreactor systems to represent in vivo intestinal microenvironments is essential
for developing regenerative medicine treatments for intestinal diseases. We have
previously developed in vitro human intestinal tissue systems using a 3D porous
silk scaffold system with intestinal architectures and topographical features for
the adhesion, growth, and differentiation of intestinal cells under static
culture conditions. In this study, we designed and fabricated a multifunctional
bioreactor system that incorporates pre-epithelialized 3D silk scaffolds in a
dynamic culture environment for in vitro engineering of human intestine tissues.
The bioreactor system allows for control of oxygen levels in perfusion fluids
(aerobic simulated intestinal fluid (SIF), microaerobic SIF, and anaerobic SIF),
while ensuring control over the mechanical and chemical microenvironments present
in native human intestines. The bioreactor system also enables 3D cell culture
with spatial separation and cultivation of cocultured epithelial and stromal
cells. Preliminary functional analysis of tissues housed in the bioreactor
demonstrated that the 3D tissue constructs survived and maintained typical
phenotypes of intestinal epithelium, including epithelial tight junction
formation, intestinal biomarker expression, microvilli formation, and mucus
secretion. The unique combination of a dynamic bioreactor and 3D intestinal
constructs offers utility for engineering human intestinal tissues for the study
of intestinal diseases and discovery options for new treatments.
PMID- 29333492
TI - Assessment of Crystal Morphology on Uptake, Particle Dissolution, and Toxicity of
Nanoscale Titanium Dioxide on Artemia salina.
AB - Knowledge of nanomaterial toxicity is critical to avoid adverse effects on human
and environment health. In this study, the influences of crystal morphology on
physico-chemical and toxic properties of nanoscale TiO2 (n-TiO2) were
investigated. Artemia salina were exposed to anatase, rutile and mixture
polymorphs of n-TiO2 in seawater. Short-term (24 h) and long-term (96 h)
exposures were conducted in 1, 10 and 100 mg/L suspensions of n-TiO2 in the
presence and absence of food. Anatase form had highest accumulation followed by
mixture and rutile. Presence of food greatly reduced accumulation. n-TiO2
dissolution was not significant in seawater (p<0.05) nor was influenced from
crystal structure. Highest toxic effects occurred in 96h exposure in the order of
anatase > mixture > rutile. Mortality and oxidative stress levels increased with
increasing n-TiO2 concentration and exposure time (p<0.05). Presence of food in
the exposure medium alleviated the oxidative stress, indicating that deprivation
from food could promote toxic effects of n-TiO2 under long-term exposure.
PMID- 29333493
TI - A quality improvement project aimed at adapting primary care to ensure the
delivery of evidence-based psychotherapy for adult anxiety.
AB - Primary care patients frequently present with anxiety with prevalence ratios up
to 30%. Brief cognitive-behavioural therapy (CBT) has been shown in meta-analytic
studies to have a strong effect size in the treatment of anxiety. However, in
surveys of anxious primary care patients, nearly 80% indicated that they had not
received CBT. In 2010, a model of CBT (Coordinated Anxiety Learning and
Management (CALM)) adapted to primary care for adult anxiety was published based
on results of a randomised controlled trial. This project aimed to integrate an
adaptation of CALM into one primary care practice, using results from the
published research as a benchmark with the secondary intent to spread a
successful model to other practices. A quality improvement approach was used to
translate the CALM model of CBT for anxiety into one primary care clinic. Plan-Do
Study-Act steps are highlighted as important steps towards our goal of comparing
our outcomes with benchmarks from original research. Patients with anxiety as
measured by a score of 10 or higher on the Generalized Anxiety Disorder 7 item
scale (GAD-7) were offered CBT as delivered by licensed social workers with
support by a PhD psychologist. Outcomes were tracked and entered into an
electronic registry, which became a critical tool upon which to adapt and improve
our delivery of psychotherapy to our patient population. Challenges and
adaptations to the model are discussed. Our 6-month response rates on the GAD-7
were 51%, which was comparable with that of the original research (57%). Quality
improvement methods were critical in discovering which adaptations were needed
before spread. Among these, embedding a process of measurement and data entry and
ongoing feedback to patients and therapists using this data are critical step
towards sustaining and improving the delivery of CBT in primary care.
PMID- 29333494
TI - Ensuring adequate vascular access in patients with major trauma: a quality
improvement initiative.
AB - Ensuring adequate vascular access in major trauma patients prior to
decompensative physiological processes is crucial to patient outcomes. Most
protocols suggest achieving two 18-gauge or larger intravenous lines immediately
in patients with major trauma. We discuss a quality improvement approach to
ensure that >90% of patients with major trauma (as defined by an injury severity
score >=12) at a level one trauma centre receive timely and adequate fluid
access. Applying Donabedian principles for process improvement, we used the
Alberta Trauma Registry to perform a 4-month chart audit on patients with major
trauma at the University of Alberta Hospital. Background data were supported with
a formal root cause analysis to outline the problems and generate plan, do, study
and act (PDSA) rapid change cycles. These PDSA cycles were then implemented over
the course of 2 months to alter system and personnel barriers to care, thereby
ensuring that patients with major trauma received adequate vascular access for
fluid resuscitation. This was followed by a 6-month sustainability assessment.
The percentage of patients with major trauma who received adequate fluid access
went from a mean of 55.5% to >90% in 2 months and was sustained at or greater
than 90% for 6 consecutive months. The formal application of quality improvement
processes is uncommon in trauma care but is much needed to ensure success and
sustainability of quality initiatives. Planning including engagement and
prechange awareness is crucial to staff engagement, change, and sustainment.
Formal quality improvement and change management techniques can elicit rapid and
sustainable changes in trauma care. We provide a framework for change to increase
compliance with fluid access in patients with major trauma.
PMID- 29333495
TI - Integrating prevention and health promotion in a London prison.
AB - Many people enter prison with poor health from a background of deprivation and
with unhealthy lifestyle habits, yet spending time in prisons is often actively
detrimental to health. There is therefore a clear value in providing high-quality
health promotion services in prisons that are effective at reaching those who
need support to improve their lifestyle. The health promotion service at HMP
Brixton provides a health trainers clinic to address lifestyle issues but found
that it was sometimes challenging to identify appropriate patients and that the
service was inefficient as a result. Analysis of our referral sources suggested
that taking steps to increase the proportion of referrals made during screening
and other clinics might lead to more appropriate and engaged patients. In this
study, we set out to use quality improvement methods to increase referral from
these sources. This involved improvements to the processes involved in delivering
National Health Service Health Checks that were the primary source of referrals
for health trainers and by improving links between the health trainer team and
other clinicians. The changes were successful in increasing referrals from these
sources. This work was completed during a period of exceptional disruption in the
prison service and is relevant to secure healthcare sites that aim to ensure
prevention activities are efficient and targeted.
PMID- 29333496
TI - Improving the wait time to consultation at the emergency department.
AB - Prolonged wait times at the emergency department (ED) are associated with
increased morbidity and mortality, and decreased patient satisfaction. Reducing
wait times at the ED is challenging. The objective of this study is to determine
if the implementation of a series of interventions would help decrease the wait
time to consultation (WTC) for patients at the ED within 6 months. Interventions
include creation of a common board detailing work output, matching manpower to
patient arrivals and adopting a team-based model of care. A retrospective
analysis of the period from January 2015 to May 2016 was undertaken to define
baseline duration for WTC. Rapid PDSA (Plan, Do, Study, Act) cycles were used to
implement a series of interventions, and changes in wait time were tracked, with
concurrent patient load, rostered manpower and number of admissions from ED.
Results of the interventions were tracked from 1 October 2016 to 30 April 2017.
There was improvement in WTC within 6 months of initiation of interventions. The
improvements demonstrated appeared consistent and sustained. The average 95th
centile WTC decreased by 38 min to 124 min, from the baseline duration of 162
min. The median WTC improved to 21 min, compared with a baseline timing of 24
min. The improvements occurred despite greater patient load of 4317 patients per
month, compared with baseline monthly average of 4053 patients. There was no
increase in admissions from ED and no change in the amount of ED manpower over
the same period. We demonstrate how implementation of low-cost interventions,
enabling transparency, equitable workload and use of a team-based care model can
help to bring down wait times for patients. Quality improvement efforts were
sustained by employing a data-driven approach, support from senior clinicians and
providing constant feedback on outcomes.
PMID- 29333497
TI - Work efficiency improvement of >90% after implementation of an annual inpatient
blood products administration consent form.
AB - Paediatric haematology, oncology and bone marrow transplant (BMT) patients
frequently require transfusion of blood products. Our institution required a new
transfusion consent be obtained every admission. The objectives of this project
were to: revise inpatient blood products consent form to be valid for 1 year,
decrease provider time spent consenting from 15 to <5 min per admission, and
improve provider frustration with the consent process. Over 6 months, we
determined the average number of hospitalisations requiring transfusions in a
random sampling of haematology/oncology/BMT inpatients. We surveyed nurses and
providers regarding frustration levels and contact required regarding consents.
Four and 12 months after implementation of the annual consent, providers and
nurses were resurveyed, and new inpatient cohorts were assessed. Comparison of
preintervention and postintervention time data allowed calculation of provider
time reduction, a surrogate measure of improved work efficiency. Prior to the
annual consent, >33 hours were spent over 6 months obtaining consent on 40
patients, with >19 hours spent obtaining consent when no transfusions were
administered during admission. Twelve months after annual consent implementation,
97.5% (39/40) of analysed patients had a completed annual blood products
transfusion consent and provider work efficiency had improved by 94.6% (>30
hours). Although several surveyed variables improved following annual consent
implementation, provider frustration with consent process remained 6 out of a max
score of 10, the same level as prior to the intervention. Development of an
annual inpatient blood products consent form decreased provider time from 15 to
<1 min per admission, decreased consenting numbers and increased work efficiency
by >90%.
PMID- 29333498
TI - Impact of pharmacist-led antibiotic stewardship program in a PICU of low/middle
income country.
PMID- 29333499
TI - Sick Note to Fit Note: one trust's project to improve usage by hospital
clinicians.
AB - Introduction: In April 2010, the government introduced a new Statement of Fitness
to Work or 'Fit Note' for patients requiring time off of work or adaptations to
their work due to illness. Responsibility to issue these documents has shifted
from primary to secondary care. Hospital clinicians are required to issue for
inpatients and for outpatients where clinical responsibility has not been taken
over by the general practitioner (GP). However, awareness of this change is
lacking. Misdirecting patients to their GP for the sole purpose of receiving a
'Fit Note' is an unnecessary use of appointment time and negatively impacts on
patients. King's College Hospital NHS Trust receives a number of quality alerts
from primary care regarding this issue. Methods: A trust-wide educational
initiative was designed and implemented to increase staff awareness of Fit Notes
and their correct usage in order to reduce the number of patients being
misdirected to their GP to obtain one. Interventions included direct staff
engagement, a trust-wide promotional campaign and creation of an electronic
version of the document. Results: Uptake of the electronic version of the Fit
Note has steadily increased and there has been a fall in the number of quality
alerts received by the trust. However, staff awareness on the whole remains low.
Conclusions: Patients being misdirected to their general practice for Fit Notes
is an important issue and one on which the baseline level of awareness among
hospital clinicians is low. Challenges during this intervention have been in
penetrating a trust of this size and getting the message across to staff.
However, digitising the Fit Note can help to increase its use.
PMID- 29333500
TI - Improving the Written Medical Handover.
AB - The handover of large numbers of medical patients, during on call periods when
staffing levels are reduced, is a challenge for all acute medical services. At
the Royal Cornwall Hospital, a large district general hospital, we identified
that foundation doctors were reviewing medical inpatients during weekend on call
periods with limited written handover information. We chose to address this
problem by developing an intervention, a weekend handover sticker, and piloting
it. We used the review of documentation to measure improvement and feedback from
users to assess the processes involved. Use of the weekend handover form improved
the written communication between weekday and weekend teams. The number of
weekend plans documented in the notes increased from 15% to 84% and the provision
of a patient summary within the last 7 days increased from 26% to 94%. The
feedback from users confirmed it was a useful intervention and 100% (15/15) of
doctors and nurses responded positively to the question "Do you think the weekend
sticker should be introduced and used at the weekend for all medical patients?"
The feedback also identified concerns regarding additional workload for weekday
ward staff and this has led to ongoing work to try and ensure that the weekend
handover form continues to be used effectively to maintain an improved level of
written handover information for on call staff. While we have not included a
direct measure of patient care, we hope that by improving the quality of written
handover information we are acting to ensure patient information is shared
effectively, with likely positive impact on patient care.
PMID- 29333501
TI - Feasibility of conducting intradermal vaccination campaign with inactivated
poliovirus vaccine using Tropis intradermal needle free injection system,
Karachi, Pakistan.
AB - Background: Administration of intradermal fractional dose of inactivated
poliovirus vaccine (fIPV) has proven to be safe and immunogenic; however, its
intradermal application using needle and syringe is technically difficult and
requires trained personnel. Methods: We assessed feasibility of conducting an
intradermal fIPV campaign in polio high risk neighborhood of Karachi using Tropis
needle-free injector. During the one-day fIPV campaign, we measured average
"application time" to administer fIPV with Tropis, collected ergonomic
information and measured vaccine wastage. Results: Eleven vaccinator teams, after
two-day training, immunized 582 children between 4 months and 5 years of age.
Average "application time" ranged from 35-75 seconds; the "application time"
decreased with the number of children vaccinated from 68 to 38 seconds between
1st and 30th child. 10/11 (91%) vaccinator teams found no ergonomic issues; 1/11
(9%) assessed that it was not easy to remove air bubbles when filling the device.
There was 0% vaccine loss reported. No adverse events following immunizations
were reported. Interpretation: We demonstrated that it is feasible, safe and
efficient to use Tropis for the administration of fIPV in a campaign setting.
PMID- 29333502
TI - Unresectable cutaneous squamous cell carcinoma of the forehead with MLH1 mutation
showing dramatic response to Programmed Cell Death Protein 1 Inhibitor Therapy.
AB - Treatment of refractory, unresectable cutaneous squamous cell carcinoma presents
a great challenge in head and neck oncology with poor prognosis. Prior case
reports have shown off-label pembrolizumab, a programed cell death receptor
antagonist, can be effective in unresectable cutaneous squamous cell carcinoma.
Furthermore, prior reports have suggested enhanced efficacy when high mutational
burden is present. In this study we present a severe case of unresectable
cutaneous squamous cell carcinoma invading the orbit and cavernous sinus with
documented tumor MLH1 mutation. The patient had a complete response to
palliative, off-label pembrolizumab therapy.
PMID- 29333503
TI - The Effect of a Vegan versus AHA DiEt in Coronary Artery Disease (EVADE CAD)
trial: study design and rationale.
AB - Background: Multiple studies demonstrate the benefit of a vegan diet on
cardiovascular risk factors when compared to no intervention or usual dietary
patterns. The aim of this study is to evaluate the effect of a vegan diet versus
the American Heart Association (AHA)-recommended diet on inflammatory and
glucometabolic profiles in patients with angiographically defined coronary artery
disease (CAD). Study Design: This study is a randomized, open label, blinded end
point trial of 100 patients with CAD as defined by >=50% diameter stenosis in a
coronary artery >=2 mm in diameter on invasive angiography. Participants are
randomized to 8 weeks of either a vegan or AHA-recommended diet (March 2014 and
February 2017). Participants are provided weekly groceries that adhere to the
guidelines of their diet. The primary endpoint is high sensitivity C-reactive
concentrations. Secondary endpoints include anthropometric data, other markers of
inflammation, lipid parameters, glycemic markers, endothelial function, quality
of life data, and assessment of physical activity. Endpoints are measured at each
visit (baseline, 4 weeks, and 8 weeks). Dietary adherence is measured by two
weekly 24-hour dietary recalls, a 4-day food record during the week prior to each
visit, and both plasma and urine levels of trimethylamine-N-oxide at each visit.
Conclusion: This study is the first to comprehensively assess multiple indices of
inflammation and glucometabolic profile in a rigorously conducted randomized
trial of patients with CAD on a vegan versus AHA-recommended diet.
PMID- 29333504
TI - Community-based physical activity as adjunctive smoking cessation treatment:
Rationale, design, and baseline data for the Lifestyle Enhancement Program (LEAP)
randomized controlled trial.
AB - Despite advances in behavioral and pharmacological treatment for tobacco use and
dependence, quit rates remain suboptimal. Increasing physical activity has shown
some promise as a strategy for improving cessation outcomes. However, initial
efficacy studies focused on intensive, highly structured exercise programs that
may not be applicable to the general population of smokers. We describe the
rationale and study design and report baseline participant characteristics from
the Lifestyle Enhancement Program (LEAP), a two-group, randomized controlled
trial. Adult smokers who engaged in low levels of leisure time physical activity
were randomly assigned to treatment conditions consisting of an individualized
physical activity intervention delivered by health fitness instructors in
community-based exercise facilities or an equal contact wellness control. All
participants received standard cognitive behavioral smoking cessation counseling
combined with nicotine replacement therapy. The primary outcomes are seven-day
point prevalence abstinence at seven weeks, six- and 12 months. Secondary
outcomes include self-reported physical activity, dietary intake, body mass
index, waist circumference, percent body fat, and nicotine withdrawal symptoms.
Participants consist of 392 sedentary smokers (mean [standard deviation] age =
44.6 [10.2] = years; 62% female; 31% African American). Results reported here
provide information regarding experiences recruiting smokers willing to change
multiple health behaviors including smoking and physical activity.
PMID- 29333505
TI - Toxicological Implications of Released Particulate Matter during Thermal
Decomposition of Nano-Enabled Thermoplastics.
AB - Nano-enabled thermoplastics are part of the growing market of nano-enabled
products (NEPs) that have vast utility in several industries and consumer goods.
The use and disposal of NEPs at their end of life has raised concerns about the
potential release of constituent engineered nanomaterials (ENMs) during thermal
decomposition and their impact on environmental health and safety. To investigate
this issue, industrially relevant nano-enabled thermoplastics including
polyurethane, polycarbonate, and polypropylene containing carbon nanotubes (0.1
and 3% w/v, respectively), polyethylene containing nanoscale iron oxide (5% w/v),
and ethylene vinyl acetate containing nanoscale titania (2 and 5% w/v) along with
their pure thermoplastic matrices were thermally decomposed using the recently
developed lab based Integrated Exposure Generation System (INEXS). The life cycle
released particulate matter (called LCPM) was monitored using real time
instrumentation, size fractionated, sampled, extracted and prepared for
toxicological analysis using primary small airway epithelial cells to assess
potential toxicological effects. Various cellular assays were used to assess
reactive oxygen species and total glutathione as measurements of oxidative stress
along with mitochondrial function, cellular viability, and DNA damage. By
comparing toxicological profiles of LCPM released from polymer only (control)
with nano-enabled LCPM, potential nanofiller effects due to the use of ENMs were
determined. We observed associations between NEP properties such as the percent
nanofiller loading, host matrix, and nanofiller chemical composition and the
physico-chemical properties of released LCPM, which were linked to biological
outcomes. More specifically, an increase in percent nanofiller loading promoted a
toxicological response independent of increasing LCPM dose. Importantly,
differences in host matrix and nanofiller composition were shown to enhance
biological activity and toxicity of LCPM. This work highlights the importance of
assessing the toxicological properties of LCPM and raises environmental health
and safety concerns of nano-enabled products at their end of life during thermal
decomposition/incineration.
PMID- 29333507
TI - Platinum open access journal in urology.
PMID- 29333508
TI - Role of cytoreductive nephrectomy in the targeted therapy era: A systematic
review and meta-analysis.
AB - Purpose: To determine the effectiveness and harm of cytoreductive nephrectomy
versus no intervention in patients with metastatic renal carcinoma who undergo
targeted therapy to improve overall survival. Materials and Methods: A search
strategy was conducted in the MEDLINE, CENTRAL, Embase, HTA, DARE, NHS, and
LILACS databases. Searches were also conducted for unpublished literature through
references from relevant articles identified through the search, conferences,
thesis databases, OpenGrey, Google Scholar, and clinicaltrials.gov, among others.
Studies were included without language restrictions. The risk of bias assessment
was made by using a modified Cochrane Collaboration tool. A meta-analysis of
fixed effects was conducted. The expected outcomes were overall survival, quality
of life, adverse effects, mortality, and progression- free survival. The measure
of the effect was the hazard ratio (HR) with a 95% confidence interval (CI). The
planned comparison was cytoreductive nephrectomy versus no intervention. Results:
A total of 22,507 patients were found among seven studies. Seven studies were
included in the qualitative analysis (eight publications) and five in the
quantitative analysis for overall survival. One study reported progression-free
survival and one reported targeted therapy toxicities. A low risk of bias was
shown for most of the study items. The HR for overall survival was 0.58 (95% CI,
0.50 to 0.65) favoring cytoreductive nephrectomy compared with no intervention.
Conclusions: Cytoreductive nephrectomy is effective for improving overall
survival in patients with metastatic renal carcinoma who undergo targeted therapy
compared with no intervention.
PMID- 29333509
TI - Rate and association of lower urinary tract infection with recurrence after
transurethral resection of bladder tumor.
AB - Purpose: To evaluate the rate of pyuria and bacteriuria after transurethral
resection of bladder tumor (TURBT). Materials and Methods: We retrospectively
evaluated data obtained from 363 patients who underwent TURBT between October
2012 and December 2013 at Seoul National University Hospital. Urinalysis and
urine culture were assessed at 3, 6, 12, and 24 months postoperatively. Primary
endpoint was the rate of bacteriuria (>=105/mL in a midstream) and pyuria (white
blood cells >=5/high-power field). Results: We analyzed 306 patients who were
eligible for the study. Pyuria was present in 23.5% of patients in the 3rd
postoperative month and in 31.7% of patients in the 24th postoperative month.
Bacteriuria was present in 1.3% of patients in the 3rd postoperative month and in
2.6% of patients in the 24th postoperative month. Among urothelial carcinoma
patients (n=220), 24.1% showed pyuria and 1.8% showed bacteriuria at the 3rd
postoperative month. We found that 31.8% showed pyuria and 3.2% showed
bacteriuria at the 24th postoperative month. There was no significant difference
in the rate of pyuria and bacteriuria between the intravesical treatment group
and the no-treatment group. Multivariate analysis demonstrated that pyuria in the
3rd postoperative month (odd ratio [OR], 2.254; p=0.039), tumor multiplicity (OR,
3.331; p=0.001), and the absence of intravesical treatment (OR, 4.927; p=0.001)
increases the risk of tumor recurrence. Conclusions: A significant proportion of
patients showed pyuria after TURBT during the follow-up period. Additionally,
presence of pyuria in the short-term follow-up period after TURBT constitutes a
risk factor for recurrence of bladder cancer.
PMID- 29333510
TI - Factors associated with testosterone recovery after androgen deprivation therapy
in patients with prostate cancer.
AB - Purpose: We investigated factors affecting testosterone recovery after androgen
deprivation therapy (ADT) withdrawal in patients with prostate cancer. Materials
and Methods: The medical records of patients who underwent radical prostatectomy
with ADT were retrospectively reviewed. In all, 221 patients were included in the
analysis. Testosterone recovery was defined as supra-castration (SC)
(testosterone levels in serum >50 ng/dL) or out of hypogonadism (OH) (>300 ng/dL)
after ADT withdrawal. Kaplan-Meier analyses were used to estimate testosterone
recovery after ADT cessation. Cox regression analyses were used to determine the
factors affecting the recovery of testosterone. Results: After ADT, 206 patients
(93.2%) recovered to the SC level and 122 patients (55.2%) recovered to the OH
level. Patients treated with ADT for <=18 months recovered to OH in a mean of 6.8
months (74.6%), but patients treated with ADT for >18 months recovered in a mean
of 9.7 months (27.5%). In multivariate analyses, age (hazard ratio [HR], 0.915;
p<0.001), serum level of sex hormone-binding globulin (SHBG) (HR, 1.015;
p=0.002), initial testosterone level (HR, 1.002; p=0.002), and ADT duration (HR,
0.915; p<0.001) were associated with recovery to the OH level after ADT
withdrawal, and hypertension (HR, 0.697; p=0.029) and duration of ADT (HR, 0.979;
p=0.012) were significantly associated with recovery to SC. Conclusions: In
patients treated with ADT for <=18 months, testosterone recovers to the OH level
more often and faster after ADT cessation. Age, SHBG level, initial testosterone
level, and ADT duration are associated with testosterone recovery.
PMID- 29333511
TI - Evaluating the importance of different computed tomography scan-based factors in
predicting the outcome of extracorporeal shock wave lithotripsy for renal stones.
AB - Purpose: To evaluate the impact of various computed tomography scan-based
parameters of renal stones on the outcome of extracorporeal shock wave
lithotripsy (ESWL). Materials and Methods: We conducted a retrospective study of
patients who underwent ESWL for renal stones (sized 5-20 mm) from January 2013 to
December 2016. We evaluated body mass index, location of the stone, skin-to-stone
distance (SSD), stone attenuation value (SAV), stone diameter, Hounsfield
density, stone area, and stone volume. Statistical analysis was done and
significance was confirmed by multivariate logistic regression analysis. Results:
Of the 203 patients 122 (60.1%) had successful clearance of the stone. The
presence of a double J stenting, a lower pole location, a higher SAV, higher
Hounsfield density, larger stone area, larger stone diameter, and higher stone
volume were negative predictors of ESWL outcome. When these parameters were
analyzed with multivariate logistic regression analysis, stone location, SSD, and
SAV were the only significant independent predictors of the outcome of ESWL.
Conclusions: Stone location, SSD, and SAV are reliable and strong predictors of
ESWL outcome for the treatment of renal stones.
PMID- 29333512
TI - Fourier transform infrared spectroscopy for analysis of kidney stones.
AB - Purpose: To compare the results of a chemical method of kidney stone analysis
with the results of Fourier transform infrared (FT-IR) spectroscopy. Materials
and Methods: Kidney stones collected between June and October 2015 were
simultaneously analyzed by chemical and FT-IR methods. Results: Kidney stones
(n=449) were collected from patients from 1 to 81 years old. Most stones were
from adults, with only 11.5% from children (aged 3-16 years) and 1.5% from
children aged <2 years. The male to female ratio was 4.6. In adults, the calcium
oxalate stone type, calcium oxalate monohydrate (COM, n=224), was the most common
crystal, followed by uric acid and calcium oxalate dihydrate (COD, n=83). In
children, the most frequently occurring type was predominantly COD (n=21),
followed by COM (n=11), ammonium urate (n=10), carbonate apatite (n=6), uric acid
(n=4), and cystine (n=1). Core composition in 22 stones showed ammonium urate
(n=2), COM (n=2), and carbonate apatite (n=1) in five stones, while uric acid
crystals were detected (n=13) by FT-IR. While chemical analysis identified 3
stones as uric acid and the rest as calcium oxalate only. Agreement between the
two methods was moderate, with a kappa statistic of 0.57 (95% confidence
interval, 0.5-0.64). Disagreement was noted in the analysis of 77 stones.
Conclusions: FT-IR analysis of kidney stones can overcome many limitations
associated with chemical analysis.
PMID- 29333513
TI - Can feeling of incomplete bladder emptying reflect significant postvoid residual
urine? Is it reliable as a symptom solely?
AB - Purpose: The main objective of this study was to reveal the relationship between
lower urinary tract symptoms (LUTS) and post-void residual (PVR) urine volume.
Materials and Methods: Between October 2014 and February 2015, older than 40
years patients were included in this study. Volunteers filled out a questionnaire
consisted of demographic characteristics, comorbidities, medications, history of
surgery and LUTS. Volunteers were undergone PVR measurement with transabdominal
ultrasonography. The relationship between symptoms, demographic characteristics
and PVR were analyzed. Results: A total of 939 patients (756 men and 183 women)
were enrolled in this study. There was a positive correlation between the
sensation of incomplete bladder emptying and PVR volume in all age groups of
women (p=0.0001). However such a relationship was found only over the age of 60
in the subgroup analysis of men (p=0.001). PVR volume increased in men by age
(0.65 mL per year of age, p=0.011). In men, voiding symptoms and urgency were
associated with a high PVR volume. In women, storage and voiding symptoms (except
slow stream and terminal dribble) did not correlate with PVR volume. Conclusions:
Our study showed that all men over the age of 60 years and all women with the
complaint of feeling of incomplete emptying should undergone PVR measurement.
Women with the complaint of poor stream and men mainly with voiding symptoms are
other candidates in whom PVR measurement would be considered as an important tool
in the clinical management and follow-up.
PMID- 29333514
TI - What is the fate of artificial urinary sphincters among men undergoing repetitive
bladder cancer treatment?
AB - Purpose: Functional characteristics and durability of the artificial urinary
sphincter (AUS) among patients who develop bladder cancer has been poorly
characterized. We sought to evaluate AUS outcomes among patients subsequently
diagnosed with bladder cancer, in order to describe device survivability when
subject to diagnostic and therapeutic procedures such as cystoscopy,
transurethral resection, and cystectomy. Materials and Methods: We
retrospectively reviewed 1,803 male patients treated with AUS surgery at a single
institution between 1983-2014. We describe AUS device outcomes among patients
undergoing surveillance and treatment for bladder cancer. Results: Following AUS
placement, 14 (0.8%) patients were subsequently diagnosed with and treated for
bladder cancer and 4 patients with bladder cancer undergoing treatment and
screening, subsequently received AUS placement. The median follow-up from device
placement was 7.2 years (interquartile range [IQR], 2.8-11.5), and the median
time from AUS placement to bladder cancer diagnosis was 6 (IQR, 0-9). There were
a total of 8 primary and 1 secondary devices failures. Despite a median of 2
diagnostic cystoscopies (IQR, 1-6) and 0 bladder tumor resections (IQR, 0-0) per
patient following device implantation, only 1 (5.6%) patient experienced an
iatrogenic erosion related to urethral manipulation. Among those undergoing
cystectomy (n=4), 1 device was left in situ without complication. Conclusions:
Bladder cancer surveillance and treatment with an AUS device in place appears to
confer minimal additional risk to AUS survival. Careful attention should be given
to device deactivation and use of the smallest caliber instruments available to
minimize the risk of iatrogenic urethral erosion.
PMID- 29333506
TI - Murine Models of Heart Failure with Preserved Ejection Fraction: a "Fishing
Expedition".
AB - Heart failure with preserved ejection fraction (HFpEF) is characterized by signs
and symptoms of HF in the presence of a normal left ventricular (LV) ejection
fraction (EF). Despite accounting for up to 50% of all clinical presentations of
HF, the mechanisms implicated in HFpEF are poorly understood, thus precluding
effective therapy. The pathophysiological heterogeneity in the HFpEF phenotype
also contributes to this disease and likely to the absence of evidence-based
therapies. Limited access to human samples and imperfect animal models that
completely recapitulate the human HFpEF phenotype have impeded our understanding
of the mechanistic underpinnings that exist in this disease. Aging and
comorbidities such as atrial fibrillation, hypertension, diabetes and obesity,
pulmonary hypertension and renal dysfunction are highly associated with HFpEF.
Yet, the relationship and contribution between them remains ill-defined. This
review discusses some of the distinctive clinical features of HFpEF in
association with these comorbidities and highlights the advantages and
disadvantage of commonly used murine models, used to study the HFpEF phenotype.
PMID- 29333515
TI - Changes in autonomic nervous system activity after treatment with alpha-blocker
in men with lower urinary tract symptoms.
AB - Purpose: To determine changes in autonomic nervous system activity after
treatment in men with lower urinary tract symptoms (LUTS), we evaluated changes
in patients' symptoms, uroflowmetry, and heart rate variability (HRV) after
treatment with alpha-blockers for 12 weeks. Materials and Methods: Ninety-five
men who had LUTS (International Prostate Symptom Score [IPSS] >=8) were included
in this study. We divided them into two groups on the basis of a low
frequency/high frequency (LF/HF) ratio of 1.6. After treatment with Xatral XL
(Handok Inc., Korea) 10 mg for 3 months, we rechecked their IPSS, uroflowmetry,
HRV and compared these with the baseline measurements. Results: Fifty-four men
were assigned to the low LF/HF group (group A: LF/HF <=1.6) and 41 men to the
high LF/HF group (group B: LF/HF >1.6). At baseline and 12 weeks, none of the
parameters differed significantly between the groups except for HF, which is one
of the parameters of HRV. IPSS, the IPSS-voiding subscore, and the IPSS-storage
subscore decreased and maximal uroflow increased significantly after 12 weeks of
treatment. Whereas the baseline LF/HF ratio increased from 0.89+/-0.407 to 1.80+/
1.804 after treatment in group A, it decreased from 3.93+/-5.471 to 1.79+/-1.153
in group B. Conclusions: The efficacies of Xatral XL were clear in both groups.
We found that the LF/HF ratio in the two groups merged to a value of
approximately 1.79 after treatment. We suggest that this could be a clue to the
importance of balance in autonomic nervous system activity in men with LUTS.
PMID- 29333516
TI - Comparison of penile length at 6-24 months between children with unilateral
cryptorchidism and a healthy normal cohort.
AB - Purpose: Urologic diseases affected by testosterone can be associated with
smaller penis size compared to the normal population. We sought to compare penile
length in children with unilateral cryptorchidism and normative data from a
cohort of healthy Korean boys. Materials and Methods: This study was performed in
259 Korean boys (212, normal cohort; 47, cryptorchidism) aged 6-24 months, each
of whom had been brought to an outpatient clinic at one of five tertiary
hospitals (Gyeongsangnam-do Province) between April 2014 and June 2015. Penile
length was measured via stretched penile length (SPL) and testicular size was
measured using orchidometry (mL). Results: SPL in children with cryptorchidism
was significantly shorter compared to a cohort of healthy Korean boys aged 6-24
months (3.7+/-0.5 cm and 4.3+/-0.8 cm, p<0.001), although there were no
differences with regard to height, body weight and contralateral testicular size
between the two groups. According to the stratified ages (6-12, 12-18, and 18-24
months), SPL in children with cryptorchidism was persistently shorter at their
ages than those without. Conclusions: It might be that the penile length aged 6
24 months of children with unilateral cryptorchidism is shorter than that of a
cohort of healthy Korean boys.
PMID- 29333517
TI - Safety and feasibility of platelet rich fibrin matrix injections for treatment of
common urologic conditions.
AB - Purpose: Autologous platelet rich plasma (PRP) is used increasingly in a variety
of settings. PRP injections have been used for decades to improve angiogenesis
and wound healing. They have also been offered commercially in urology with
little to no data on safety or efficacy. PRP could theoretically improve multiple
urologic conditions, such as erectile dysfunction (ED), Peyronie's disease (PD),
and stress urinary incontinence (SUI). A concern with PRP, however, is early
washout, a situation potentially avoided by conversion to platelet rich fibrin
matrix (PRFM). Before clinical trials can be performed, safety analysis is
desirable. We reviewed an initial series of patients receiving PRFM for urologic
pathology to assess safety and feasibility. Materials and Methods: Data were
reviewed for patients treated with PRFM at our center from November 2012 to July
2017. Patients were observed immediately post-injection and at follow-up for
complications and tolerability. Where applicable, International Index of Erectile
Function (IIEF-5) scores were reviewed before and after injections for ED and/or
PD. Pad use data was collected pre/post injection for SUI. Results: Seventeen
patients were identified, with a mean receipt of 2.1 injections per patient. Post
procedural minor adverse events were seen in 3 men, consisting of mild pain at
injection site and mild penile bruising. No patients experienced complications at
follow-up. No decline was observed in men completing pre/post IIEF-5 evaluations.
Conclusions: PRFM appears to be a safe and feasible treatment modality in
patients with urologic disease. Further placebo-controlled trials are warranted.
PMID- 29333518
TI - Letter to the editor: Urethral strictures after bipolar transurethral resection
of prostate may be linked to slow resection rate.
PMID- 29333519
TI - The authors reply: Urethral strictures after bipolar transurethral resection of
prostate may be linked to slow resection rate.
PMID- 29333520
TI - Application of epigenetic data in human health risk assessment.
AB - Despite the many recent advances in the field of epigenetics, application of this
knowledge in environmental health risk assessment has been limited. In this
paper, we identify opportunities for application of epigenetic data to support
health risk assessment. We consider current applications and present a vision for
the future.
PMID- 29333521
TI - Nanomaterials for convection-enhanced delivery of agents to treat brain tumors.
AB - Nanomaterials represent a promising and versatile platform for the delivery of
therapeutics to the brain. Treatment of brain tumors has been a long-standing
challenge in the field of neuro-oncology. The current standard of care - a
multimodal approach of surgery, radiation and chemotherapy - yields only a modest
therapeutic benefit for patients with malignant gliomas. A major obstacle for
treatment is the failure to achieve sufficient delivery of therapeutics at the
tumor site. Recent advances in local drug delivery techniques, along with the
development of highly effective brain-penetrating nanocarriers, have
significantly improved treatment and imaging of brain tumors in preclinical
studies. The major advantage of this combined strategy is the ability to optimize
local therapy, by maintaining an effective and sustained concentration of
therapeutics in the brain with minimal systemic toxicity. This review highlights
some of the latest developments, significant advancements and current challenges
in local delivery of nanomaterials for the treatment of brain tumors.
PMID- 29333522
TI - Impact of HLA Class I Alleles on Timing of HIV Rebound After Antiretroviral
Treatment Interruption.
AB - Background: Identifying host determinants associated with HIV reservoir size and
timing of viral rebound after an analytic treatment interruption (ATI) is an
important step in the search for an HIV functional cure. We performed a pooled
analysis of 103 participants from 4 AIDS Clinical Trials Group ATI studies to
identify the association between HLA class I alleles with HIV reservoir size and
viral rebound timing. Methods: Total HIV DNA and cell-associated HIV RNA (CA-RNA)
were quantified in pre-ATI peripheral blood mononuclear cell samples, and
residual plasma viremia was measured using the single-copy assay. HLA class I
typing was performed, and we generated an odds ratio (OR) of predicted HLA effect
on HIV viremia control for each individual and compared this with time to viral
rebound, and levels of HIV DNA and CA-RNA. Results: There was no significant
association between the HLA ORs and levels of HIV DNA or CA-RNA, but carriage of
protective HLA-B alleles (lower OR scores) was associated with delayed viral
rebound (P = 0.02). Higher OR scores at the HLA-C locus were associated with
longer duration of ART treatment (P = 0.02) and this trend was also seen with the
combined OR score (P < 0.01). Individuals with protective HLA-B alleles had
delayed viral rebound after treatment interruption that was not explained by
differences in baseline reservoir size. Conclusions: The results indicate the
vital role of cellular host immunity in preventing HIV rebound and the importance
of taking into account the HLA status of study participants being evaluated in
trials for an HIV cure.
PMID- 29333523
TI - Spin-orbit torques from interfacial spin-orbit coupling for various interfaces.
AB - We use a perturbative approach to study the effects of interfacial spin-orbit
coupling in magnetic multilayers by treating the two-dimensional Rashba model in
a fully three-dimensional description of electron transport near an interface.
This formalism provides a compact analytic expression for current-induced spin
orbit torques in terms of unperturbed scattering coefficients, allowing
computation of spin-orbit torques for various contexts, by simply substituting
scattering coefficients into the formulas. It applies to calculations of spin
orbit torques for magnetic bilayers with bulk magnetism, those with interface
magnetism, a normal metal/ferromagnetic insulator junction, and a topological
insulator/ferromagnet junction. It predicts a dampinglike component of spin-orbit
torque that is distinct from any intrinsic contribution or those that arise from
particular spin relaxation mechanisms. We discuss the effects of proximity
induced magnetism and insertion of an additional layer and provide formulas for
in-plane current, which is induced by a perpendicular bias, anisotropic
magnetoresistance, and spin memory loss in the same formalism.
PMID- 29333524
TI - Resonant X-ray Emission of Hexagonal Boron Nitride.
AB - The electronic structure of hexagonal boron nitride (h-BN) is explored using
measurements of x-ray absorption and resonant inelastic x-ray scattering (RIXS)
at the nitrogen K edge (1s) in tandem with calculations using many-body
perturbation theory within the GW and Bethe-Salpeter equation (BSE)
approximations. Our calculations include the effects of lattice disorder from
phonons activated thermally and from zero point energy. They highlight the
influence of disorder on near-edge x-ray spectra.
PMID- 29333525
TI - Dyslipidemia and its Correlates among HIV Infected Children on HAART Attending
Mbarara Regional Referral Hospital.
AB - Background: HAART and chronic HIV associated inflammation has been attributed to
abnormal lipids in HIV infected people. Little is known about dyslipidemia among
children in Uganda in the era of increasing Highly Active Anti Retroviral Therapy
(HAART) use. We determined the prevalence of lipid abnormalities, the correlation
of the lipid abnormalities to CD4 count, HIV clinical stage and duration on HAART
among HIV infected children. Methods: This was a cross-sectional, descriptive and
analytical study of HIV infected children age 1-17 years receiving HAART for more
than 6 months in Mbarara Regional Referral Hospital. Consent and assent were
obtained as appropriate. Sociodemographic, clinical and immunological data were
collected and recorded in a questionnaire. A blood sample was taken for lipid
profiling. Dyslipidemia was defined as any low HDL (<=40mg/dl), high LDL
(>130mg/dl), high TG (>130mg/dl) and a high total cholesterol (>200mg/dl) or a
combination of these in the study population. The proportion of children with
dyslipidemia was calculated and logistic regression analysis for associated
factors. Results: The mean age was 118 months (SD 49 months) with 49.5% of the
children male and 62.1% had severe HIV disease at initiation of HAART. Mean
duration of HAART was 55.6 months (SD 31.2 months). The prevalence of
dyslipidemia was 74%. Among the children with dyslipidemia, 56.6% exhibited low
HDL, 22% had hypertriglyceridemia, 15.6% had high LDL and 11% had
hypercholesterolemia. We found significant association between dyslipidemia and
WHO clinical stage at initiation of HAART (AOR 2.9 1.05 - 8.45 p=0.040).
Conclusion: There was a high prevalence of dyslipidemia associated with severe
HIV disease at initiation of HAART among HIV-infected children on HAART.
PMID- 29333526
TI - Next-Generation Rapid Autopsies Enable Tumor Evolution Tracking and Generation of
Preclinical Models.
AB - Purpose: Patients with cancer who graciously consent for autopsy represent an
invaluable resource for the study of cancer biology. To advance the study of
tumor evolution, metastases, and resistance to treatment, we developed a next
generation rapid autopsy program integrated within a broader precision medicine
clinical trial that interrogates pre- and postmortem tissue samples for patients
of all ages and cancer types. Materials and Methods: One hundred twenty-three
(22%) of 554 patients who consented to the clinical trial also consented for
rapid autopsy. This report comprises the first 15 autopsies, including patients
with metastatic carcinoma (n = 10), melanoma (n = 1), and glioma (n = 4). Whole
exome sequencing (WES) was performed on frozen autopsy tumor samples from
multiple anatomic sites and on non-neoplastic tissue. RNA sequencing (RNA-Seq)
was performed on a subset of frozen samples. Tissue was also used for the
development of preclinical models, including tumor organoids and patient-derived
xenografts. Results: Three hundred forty-six frozen samples were procured in
total. WES was performed on 113 samples and RNA-Seq on 72 samples. Successful
cell strain, tumor organoid, and/or patient-derived xenograft development was
achieved in four samples, including an inoperable pediatric glioma. WES data were
used to assess clonal evolution and molecular heterogeneity of tumors in
individual patients. Mutational profiles of primary tumors and metastases yielded
candidate mediators of metastatic spread and organotropism including CUL9 and
PIGM in metastatic ependymoma and ANKRD52 in metastatic melanoma to the lung. RNA
Seq data identified novel gene fusion candidates. Conclusion: A next-generation
sequencing-based autopsy program in conjunction with a pre-mortem precision
medicine pipeline for diverse tumors affords a valuable window into clonal
evolution, metastasis, and alterations underlying treatment. Moreover, such an
autopsy program yields robust preclinical models of disease.
PMID- 29333527
TI - Impact of Genetic Ancestry on Outcomes in ECOG-ACRIN-E5103.
AB - Purpose: Racial disparity in breast cancer outcomes exists between African
American and Caucasian women in the United States. We have evaluated the impact
of genetically determined ancestry on disparity in efficacy and therapy-induced
toxicity for breast cancer patients in the context of a randomized, phase III
adjuvant trial. Patients and Methods: This study compared outcomes between 386
patients of African ancestry (AA) and 2473 patients of European ancestry (EA) in
a randomized, phase III breast cancer trial; ECOG-ACRIN-E5103. The primary
efficacy endpoint, invasive disease free survival (DFS) and clinically
significant toxicities were compared including: anthracycline-induced congestive
heart failure (CHF), taxane-induced peripheral neuropathy (TIPN), and bevacizumab
induced hypertension. Results: Overall, AAs had significantly inferior DFS
(p=0.002; HR=1.5) compared with EAs. This was significant in the estrogen
receptor-positive subgroup (p=0.03); with a similar, non-significant trend for
those who had triple negative breast cancer (TNBC; p=0.12). AAs also had
significantly more grade 3-4 TIPN (OR=2.9; p=2.4 *10-11) and grade 3-4
bevacizumab-induced hypertension (OR=1.6; p=0.02), with a trend for more CHF
(OR=1.8; p=0.08). AAs had significantly more dose reductions for paclitaxel
(p=6.6 *10-6). In AAs, dose reductions in paclitaxel had a significant negative
impact on DFS (p=0.03); whereas in EAs, dose reductions did not impact outcome
(p=0.35). Conclusion: AAs had inferior DFS with more clinically important
toxicities in ECOG-ACRIN-E5103. The altered risk to benefit ratio for adjuvant
breast cancer chemotherapy should lead to additional research with the focus
centered on the impact of genetic ancestry on both efficacy and toxicity.
Strategies to minimize dose reductions for paclitaxel, especially due to TIPN,
are warranted for this population.
PMID- 29333529
TI - Promoting resilience in diverse classrooms: The answers are not in the back of
the book.
PMID- 29333528
TI - Patterns of Metastatic Spread and Mechanisms of Resistance to Crizotinib in ROS1
Positive Non-Small-Cell Lung Cancer.
AB - PURPOSE: The ROS1 tyrosine kinase is activated through ROS1 gene rearrangements
in 1-2% of non-small cell lung cancer (NSCLC), conferring sensitivity to
treatment with the ALK/ROS1/MET inhibitor crizotinib. Currently, insights into
patterns of metastatic spread and mechanisms of crizotinib resistance among ROS1
positive patients are limited. PATIENTS AND METHODS: We reviewed clinical and
radiographic imaging data of patients with ROS1- and ALK-positive NSCLC in order
to compare patterns of metastatic spread at initial metastatic diagnosis. To
determine molecular mechanisms of crizotinib resistance, we also analyzed repeat
biopsies from a cohort of ROS1-positive patients progressing on crizotinib.
RESULTS: We identified 39 and 196 patients with advanced ROS1- and ALK-positive
NSCLC, respectively. ROS1-positive patients had significantly lower rates of
extrathoracic metastases (ROS1 59.0%, ALK 83.2%, P=0.002), including lower rates
of brain metastases (ROS1 19.4%, ALK 39.1%; P = 0.033), at initial metastatic
diagnosis. Despite similar overall survival between ALK- and ROS1-positive
patients treated with crizotinib (median 3.0 versus 2.5 years, respectively;
P=0.786), ROS1-positive patients also had a significantly lower cumulative
incidence of brain metastases (34% vs. 73% at 5 years; P<0.0001). Additionally,
we identified 16 patients who underwent a total of 17 repeat biopsies following
progression on crizotinib. ROS1 resistance mutations were identified in 53% of
specimens, including 9/14 (64%) non-brain metastasis specimens. ROS1 mutations
included: G2032R (41%), D2033N (6%), and S1986F (6%). CONCLUSIONS: Compared to
ALK rearrangements, ROS1 rearrangements are associated with lower rates of
extrathoracic metastases, including fewer brain metastases, at initial metastatic
diagnosis. ROS1 resistance mutations, particularly G2032R, appear to be the
predominant mechanism of resistance to crizotinib, underscoring the need to
develop novel ROS1 inhibitors with activity against these resistant mutants.
PMID- 29333530
TI - Transparent Flexible Active Faraday Cage Enables In Vivo Capacitance Measurement
in Assembled Microsensor.
AB - Capacitive micro-sensors such as accelerometers, gyroscopes and pressure sensors
are increasingly used in the modern electronic world. However, the in vivo use of
capacitive sensing for measurement of pressure or other variables inside a human
body suffers from significant errors due to stray capacitance. This paper
proposes a solution consisting of a transparent thin flexible Faraday cage that
surrounds the sensor. By supplying the active sensing voltage simultaneously to
the deformable electrode of the capacitive sensor and to the Faraday cage, the
stray capacitance during in vivo measurements can be largely eliminated. Due to
the transparency of the Faraday cage, the top and bottom portions of a capacitive
sensor can be accurately aligned and assembled together. Experimental results
presented in the paper show that stray capacitance is reduced by a factor of 10
by the Faraday cage, when the sensor is subjected to a full immersion in water.
PMID- 29333533
TI - Psychosocial Outcomes Among Children Following Defilement And The Caregivers
Responses To The Children's Trauma: A Qualitative Study From Nairobi Suburbs,
Kenya.
AB - Defilement is traumatic and often associated with psychosocial problems in
children, parental distress and significant social strain on family relationships
and well-being. This study aimed at examining psychosocial outcomes in defiled
children and their caregivers' perceptions of the children's trauma after
defilement. The study was carried out between June 2015 and July 2016 at Kenyatta
National Hospital and Nairobi Women's Hospital. It adopted a qualitative
descriptive design using interviews to obtain information from six purposely
selected caregivers comprising of four mothers, one father and one grandmother.
All the perpetrators were adult males and two of the defiled children were male
and 5 were female. Two of the children were siblings; a brother and his sister.
Five of the perpetrators were known to the children and one of these was the
child's biological father. The defiled children had negative outcomes in terms of
poor academic performance, low self esteem, depression and poor social
relationships. In addition one of the children contracted HIV/AIDS, two became
pregnant, one was used to traffic drugs, and another had mental retardation. The
caregivers felt significant psychosocial distress. There is therefore, need to
routinely screen for psychological, social and physical outcomes of children
exposed to defilement trauma and to always consider caregiver distress when
treating these children.
PMID- 29333531
TI - Patient-Reported Outcome Measures (PROM) as A Preoperative Assessment Tool.
AB - Aim of review: Patient-reported outcomes (PRO) on functional, social, and
behavioral factors might be important preoperative predictors of postoperative
outcomes. We conducted a literature review to explore associations of
preoperative depression, socioeconomic status, social support, functional
status/frailty, cognitive status, self-management skills, health literacy, and
nutritional status with surgical outcomes. Methods: Two electronic data bases,
including PubMed and Google Scholar, were searched linking either depression,
socioeconomic status, social support, functional status/frailty, cognitive
status, self-management skills, health literacy, or nutritional status with
surgery, postoperative complications, or perioperative period within the past 2
decades. Recent findings: Preoperative depression has been linked to
postoperative delirium, complications, persistent pain, longer lengths of stay,
and mortality. Socioeconomic status associates with overall and cancer-free
survival. Low socioeconomic status has also been connected to medication non-
compliance. Social support can predict overall and cancer- free survival, as well
as physical, social and emotional quality of life. Poor functional status and
frailty have been related to postoperative complications, longer lengths of stay,
post-discharge institutionalization, and higher costs. Preoperative cognitive
impairment also associates with self-medication management errors, postoperative
cognitive impairment, delirium, complications and mortality. In addition, a
greater tendency for reduced adherence to preoperative medication instructions
has been linked to health illiteracy. Preoperative malnutrition is prevalent and
associates with postoperative morbidity. Conclusion: Efficient and effective
assessments of social and behavioral determinants of health, functional status,
health literacy, patient's perception of health, and preferences for self
management may improve postoperative management and surgical outcomes,
particularly among vulnerable patients undergoing elective surgery who might have
subtle physical, social, or psychological deficits or challenges, otherwise
missed upon routine evaluation. Patient Reported Outcome Measures (PROMs) can be
used to effectively and efficiently collect these factors in the preoperative
period, thereby identifying areas that can be intervened preemptively. (Partially
Funded by the National Institute on Aging and the Wake Forest University Claude
D. Pepper Older Americans Independence Center.).
PMID- 29333535
TI - It is Time to Obligate the Warning Messages on Junk Food Packages and
Advertisements: A Step to live long.
PMID- 29333534
TI - The Stagnant Adaptation of Defined and Xeno-Free Culture of iPSCs in Academia.
AB - Pluripotent Stem Cells were originally derived and cultured using a feeder layer
of cells. Movements have been undertaken to transition from this method to one
more defined, high-throughput, and without xenogenic factors. Tremendous research
has been done in this area and many products have been developed, however, based
on our analysis of recent publications in stem cell related journals many in
academia are still using older methods like a feeder layer. In this short
communication, we discuss the feasibility of transitioning to defined, xeno-free
methods, how a standardized method could improve the field and industry, and that
a study bringing together multiple institutions comparing culture methods could
be done to evaluate the efficacy of these new methods.
PMID- 29333532
TI - Molecular Docking: From Lock and Key to Combination Lock.
AB - Accurate modeling of protein ligand binding is an important step in structure
based drug design, is a useful starting point for finding new lead compounds or
drug candidates. The 'Lock and Key' concept of protein-ligand binding has
dominated descriptions of these interactions, and has been effectively translated
to computational molecular docking approaches. In turn, molecular docking can
reveal key elements in protein-ligand interactions-thereby enabling design of
potent small molecule inhibitors directed against specific targets. However,
accurate predictions of binding pose and energetic remain challenging problems.
The last decade has witnessed more sophisticated molecular docking approaches to
modeling protein-ligand binding and energetics. However, the complexities that
confront accurate modeling of binding phenomena remain formidable. Subtle
recognition and discrimination patterns governed by three-dimensional features
and microenvironments of the active site play vital roles in consolidating the
key intermolecular interactions that mediates ligand binding. Herein, we briefly
review contemporary approaches and suggest that future approaches treat protein
ligand docking problems in the context of a 'combination lock' system.
PMID- 29333538
TI - Editorial: What's next after "universal" adhesives, "bioactive" adhesives?
PMID- 29333536
TI - OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in
Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling.
AB - Purpose: Optical coherence tomography angiography (OCT-A) is a newly developed
technique to visualize retinal vasculature non-invasively based on
interferometry. Although OCT-A has been used clinically, its applications in
small animal studies have been limited. This study is designed to develop and
demonstrate the feasibility of a protocol for the use of an en-face OCT-based
method to visualize and quantify retinal microvasculature in mice that can be
used for in vivo assessment of retina ischemia. Methods: A customized algorithm
was developed to extract angiographic profiles of the mouse retina from en-face
OCT using an unmodified Bioptigen Envisu R-Class OCT imaging system. En-face OCT
images were collected in living animals and then compared to images acquired
following termination of blood flow to the retina. The images were processed with
ImageJ using the raw file importer. The vessel enhancement algorithm was
developed based on a combination of local contrast enhancement, Laplacian of
Gaussian peak detection and background subtraction methods. For comparison,
fluorescein angiography (FA) was performed using Heidelberg Spectralis(r) HRA+OCT
imaging system. Results: By vessel enhancement algorithm, we successfully
extracted retinal vasculature and quantified retinal vessel branch points,
vascular area and vessel lengths with AngioTool. While the retinal neuronal
structure could be simultaneously identified and quantified using B-scan and
volumetric OCT run in the annular scanning model, the retinal vasculature in OCT
A was dramatically diminished after the animals were sacrificed, indicating en
face OCT-A signal is a measure of the blood flow. Conclusions: These studies
indicate that a novel approach to extract angiographs from en-face OCT images by
utilizing local structure enhancement can be used to provide depth-resolved
retinal vasculature distributions. Simultaneous non-invasive analysis of retinal
vessels and neurons by OCT-A and OCT may provide a novel approach to characterize
retinal ischemia accompanied by neurovascular coupling.
PMID- 29333539
TI - Past, present, and future of the IAAD.
PMID- 29333542
TI - Acceleration of bursty multiprotein target search kinetics on DNA by
colocalisation.
AB - Proteins are capable of locating specific targets on DNA by employing a
facilitated diffusion process with intermittent 1D and 3D search steps. Gene
colocalisation and coregulation-i.e. the spatial proximity of two communicating
genes-is one factor capable of accelerating the target search process along the
DNA. We perform Monte Carlo computer simulations and demonstrate the benefits of
gene colocalisation for minimising the search time in a model DNA-protein system.
We use a simple diffusion model to mimic the search for targets by proteins,
produced initially in bursts of multiple proteins and performing the first
passage search on the DNA chain. The behaviour of the mean first-passage times to
the target is studied as a function of distance between the initial position of
proteins and the DNA target position, as well as versus the concentration of
proteins. We also examine the properties of bursty target search kinetics for
varying physical-chemical protein-DNA binding affinity. Our findings underline
the relevance of colocalisation of production and binding sites for protein
search inside biological cells.
PMID- 29333543
TI - In vitro evaluation of the enantiomeric R- and S-1,1'-binaphthyl-2,2'
diaminodichlorido-Pt(ii) complexes in human Burkitt lymphoma cells: emphasis on
cellular accumulation, cytotoxicity, DNA binding, and ability to induce
apoptosis.
AB - The aim of this project is to gain insights into the uptake and cellular actions
of the enantiomeric R- and S-1,1'-binaphthyl-2,2'-diaminodichlorido-Pt(ii)
complexes (R- and S-[Pt(DABN)Cl2]) in the cisplatin-sensitive human Burkitt
lymphoma cell line (Gumbus, IC50: 1.3 +/- 0.2 MUM) and its cisplatin-resistant
sub-line (CDDPrGB, IC50: 6.6 +/- 1.2 MUM). The cellular uptakes of R- and S
[Pt(DABN)Cl2] are ca. 4-fold higher than cisplatin, and involve a transport
mechanism independent of the volume-sensitive, organic anion-channel complex,
which facilitates cisplatin accumulation. The cisplatin-resistant CDDPrGB cells
are not cross-resistant to either S- or R-[Pt(DABN)Cl2]. We also find that even
though R-[Pt(DABN)Cl2] has a higher maximal cellular uptake and binds at higher
levels to calf-thymus DNA than S-[Pt(DABN)Cl2], it appears that S-[Pt(DABN)Cl2]
is more cytotoxic for Gumbus (IC50: 0.4 +/- 0.1 MUM) compared to R-[Pt(DABN)Cl2]
(IC50: 0.7 +/- 0.3 MUM). The cellular action of R- and S-[Pt(DABN)Cl2] involves
G0/G1 cell cycle arrest and cell death involving the extrinsic and intrinsic
apoptotic pathways.
PMID- 29333537
TI - Cerebral Autoregulation in Hypertension and Ischemic Stroke: A Mini Review.
AB - Aging and chronic hypertension are associated with dysfunction in vascular smooth
muscle, endothelial cells, and neurovascular coupling. These dysfunctions induce
impaired myogenic response and cerebral autoregulation, which diminish the
protection of cerebral arterioles to the cerebral microcirculation from elevated
pressure in hypertension. Chronic hypertension promotes cerebral focal ischemia
in response to reductions in blood pressure that are often seen in sedentary
elderly patients on antihypertensive therapy. Cerebral autoregulatory dysfunction
evokes Blood-Brain Barrier (BBB) leakage, allowing the circulating inflammatory
factors to infiltrate the brain to activate glia. The impaired cerebral
autoregulation-induced inflammatory and ischemic injury could cause neuronal cell
death and synaptic dysfunction which promote cognitive deficits. In this brief
review, we summarize the pathogenesis and signaling mechanisms of cerebral
autoregulation in hypertension and ischemic stroke-induced cognitive deficits,
and discuss our new targets including 20-Hydroxyeicosatetraenoic acid (20-HETE),
Gamma-Adducin (Add3) and Matrix Metalloproteinase-9 (MMP-9) that may contribute
to the altered cerebral vascular function.
PMID- 29333544
TI - Formal total synthesis of salvianolic acid N.
AB - An efficient synthetic pathway for the total synthesis of salvianolic acid N has
been reported. The key reaction steps, the Wittig reaction for Z
stereoselectivity and an intramolecular cyclization for a seven membered ring
skeleton, have been optimized to improve the synthetic feasibility and provide
the best conditions in terms of yield. Moreover, a notable reaction is the
reaction of the deprotected allylic group with Pd catalyst. An improved overall
yield of 11% has been achieved for salvianolic acid N starting from 3,4
dimethoxybenzaldehyde in 11 steps.
PMID- 29333547
TI - Diverse bimetallic mechanisms emerging from transition metal Lewis acid/base
pairs: development of co-catalysis with metal carbenes and metal carbonyl anions.
AB - The rational development of catalytic reactions involving cooperative behavior
between two catalytic reactive sites represents a frontier area of research from
which novel reactivity and selectivity patterns emerge. Within this context, this
Feature highlights the development of a cooperative system involving transition
metal Lewis acid/base pairs. Bimetallic systems consisting of copper carbene
Lewis acids and metal carbonyl anion Lewis bases, (NHC)Cu-[MCO], are easily
synthesized from readily available organometallic building blocks (NHC = N
heterocyclic carbene; [MCO]- = metal carbonyl anion, e.g. [FeCp(CO)2]-, [Mn(CO)5]
, etc.). Stoichiometric reactivity studies indicate that the dative Cu<-M bonds
in these systems are labile towards heterolysis under mild conditions, thus
providing in situ access both to polar metal-metal bonds and to "frustrated"
transition metal Lewis acid/base pairs as dictated by reaction conditions.
Catalytic transformations ranging from C-C and C-B coupling reactions to
hydrogenation and other reductions have been developed from both manifolds:
bimetallic catalysis involving (a) binuclear intermediates engaging in
cooperative bond activation and formation, and (b) orthogonal mononuclear
intermediates that operate in either tandem or co-dependent manners. Preliminary
indications point to the future emergence of novel reactivity and selectivity
patterns as these new motifs undergo continued development, and additionally
demonstrate that the relative matching of two reactive sites provides a method
for controlling catalytic behavior. Collectively, these results highlight the
fundamental importance of exploring unconventional catalytic paradigms.
PMID- 29333548
TI - Efficient generation of an oxidopyrylium ylide using a Pd catalyst and its [5+2]
cycloadditions with several dipolarophiles.
AB - An efficient method for the generation of an oxidopyrylium ylide from 6-acetoxy-6
acetoxymethyl-2H-pyran-3(6H)-one using a Pd catalyst and [5+2] cycloadditions of
the resulting ylide are described. Among substituted styrene derivatives as
dipolarophiles, electron-rich styrenes showed higher yield (up to 80%). The [5+2]
cycloaddition reactions can also be applied to exo-methylene cyclic compounds,
and an improved method for the synthesis of polygalolide intermediate has been
demonstrated.
PMID- 29333550
TI - CuWO4 as a photocatalyst for room temperature aerobic benzylamine oxidation.
AB - The aerobic photochemical oxidation of benzylamine was carried out on the ternary
oxides CuWO4 and BiVO4 as a test proton-coupled-electron-transfer reaction in
acetonitrile. Both oxides give the coupled imine product, N
benzylidenebenzylamine, in near quantitative (98-99%) yield, with rate constants
of 0.34 h-1 g-1 and 0.70 h-1 g-1 for CuWO4 and BiVO4, respectively.
PMID- 29333551
TI - Anharmonic vibrational spectra from double incremental potential energy and
dipole surfaces.
AB - We extend the fragmentation-based double incremental expansion in FALCON
coordinates (DIF) and its linear-scaling analogue [C. Konig and O. Christiansen,
J. Chem. Phys., 2016, 145, 064105] to dipole surfaces. Thereby, we enable the
calculation of intensities in vibrational absorption spectra from these cost
efficient property surfaces. We validate the obtained potential energy and dipole
surfaces by vibrational spectra calculations employing damped response theory for
correlated vibrational coupled cluster wave functions. Our largest calculation on
a hexa-phenyl includes all 180 vibrational degrees of freedom of the system,
which illustrates the potential of both the DIF schemes for property surface
generation and the use of damped response theory from high-dimensional correlated
vibrational wave functions. Generally, we obtain good agreement between the
spectra calculated from the DIF property surfaces and the non-fragmented
analogues. Moreover, when adopting suitable electronic structure methods, good
agreement with respect to the experiment can be obtained, as shown for the
example of 5-methylfurfural and RI-MP2. In conclusion, our results illustrate
that the presented scheme with linearly scaling surfaces enables high quality
spectra, as long as reasonably sized fragments can be defined. With this work, we
push the realistic limits of vibrational spectra calculations from vibrational
wave function methods and accurate electronic structure calculations to
significantly larger systems than currently accessible.
PMID- 29333545
TI - Dynamic changes in copper homeostasis and post-transcriptional regulation of
Atp7a during myogenic differentiation.
AB - Copper (Cu) is an essential metal required for activity of a number of redox
active enzymes that participate in critical cellular pathways such as metabolism
and cell signaling. Because it is also a toxic metal, Cu must be tightly
controlled by a series of transporters and chaperone proteins that regulate Cu
homeostasis. The critical nature of Cu is highlighted by the fact that mutations
in Cu homeostasis genes cause pathologic conditions such as Menkes and Wilson
diseases. While Cu homeostasis in highly affected tissues like the liver and
brain is well understood, no study has probed the role of Cu in development of
skeletal muscle, another tissue that often shows pathology in these conditions.
Here, we found an increase in whole cell Cu content during differentiation of
cultured immortalized or primary myoblasts derived from mouse satellite cells. We
demonstrate that Cu is required for both proliferation and differentiation of
primary myoblasts. We also show that a key Cu homeostasis gene, Atp7a, undergoes
dynamic changes in expression during myogenic differentiation. Alternative
polyadenylation and stability of Atp7a mRNA fluctuates with differentiation stage
of the myoblasts, indicating post-transcriptional regulation of Atp7a that
depends on the differentiation state. This is the first report of a requirement
for Cu during myogenic differentiation and provides the basis for understanding
the network of Cu transport associated with myogenesis.
PMID- 29333552
TI - Counting DNA molecules with visual segment-based readouts in minutes.
AB - An ultrafast and extremely simple approach was proposed to count the number of
DNA molecules without any microfluidic-based device. By directly counting the
number of amplicon clusters in a capillary, the absolute amount of DNA molecules
could be easily determined.
PMID- 29333553
TI - Microwave-assisted synthesis of TEMPO-labeled hydrogels traceable with MRI.
AB - Polymer functionalization strategies have recently attracted considerable
attention for several applications in biomaterials science. In particular,
technological advancements in medical imaging have focused on the design of
polymeric matrices to improve non-invasive approaches and diagnostic accuracy. In
this scenario, the use of microwave irradiation of aqueous solutions containing
appropriate combinations of polymers is gaining increasing interest in the
synthesis of sterile hydrogels without using monomers, eliminating the need to
remove unreacted species. In this study, we developed a method for the in situ
fabrication of TEMPO-labeled hydrogels based on a one-pot microwave reaction that
can then be tracked by magnetic resonance imaging (MRI) without using toxic
compounds that could be hostile for the target tissue. Click chemistry was used
to link TEMPO to the polymeric scaffold. In an in vivo model, the system was able
to preserve its TEMPO paramagnetic activity up to 1 month after hydrogel
injection, showing a clear detectable signal on T1-weighted MRI with a
longitudinal relaxivity value of 0.29 mM s-1, comparable to a value of 0.31 mM s
1 characteristic of TEMPO application. The uncleavable conjugation between the
contrast agent and the polymeric scaffold is a leading point to record these
results: the use of TEMPO only physically entrapped in the polymeric scaffold did
not show MRI traceability even after few hours. Moreover, the use of TEMPO
labeled hydrogels can also help to reduce the number of animals sacrificed being
a longitudinal non-invasive technique.
PMID- 29333554
TI - In-cell NMR: from metabolites to macromolecules.
AB - In-cell NMR of macromolecules has gained momentum over the last ten years as an
approach that might bridge the branches of cell biology and structural biology.
In this review, we put it in the context of earlier efforts that aimed to
characterize by NMR the cellular environment of live cells and their
intracellular metabolites. Although technical aspects distinguish these earlier
in vivo NMR studies and the more recent in cell NMR efforts to characterize
macromolecules in a cellular environment, we believe that both share major
concerns ranging from sensitivity and line broadening to cell viability.
Approaches to overcome the limitations in one subfield thereby can serve the
other one and vice versa. The relevance in biomedical sciences might stretch from
the direct following of drug metabolism in the cell to the observation of target
binding, and thereby encompasses in-cell NMR both of metabolites and
macromolecules. We underline the efforts of the field to move to novel biological
insights by some selected examples.
PMID- 29333555
TI - A mechanism study on the hydrogen evolution reaction catalyzed by molybdenum
disulfide complexes.
AB - Density functional theory (DFT) calculations show that H2 evolution is attributed
to active sulfur hydrides derived from MoS2 complexes via two- or three-electron
reduction from the synthesized [(PY5Me2)MoS2]2+. Water acts as a bridge for H2
evolution from the intermolecular H+/H- coupling between sulfur hydride complexes
and hydrated protons.
PMID- 29333556
TI - Correction: Chemical analysis in saliva and the search for salivary biomarkers -
a tutorial review.
AB - Correction for 'Chemical analysis in saliva and the search for salivary
biomarkers - a tutorial review' by Kamonwad Ngamchuea, et al., Analyst, 2018,
143, 81-99.
PMID- 29333557
TI - Drop impact dynamics on slippery liquid-infused porous surfaces: influence of oil
thickness.
AB - Slippery liquid-infused porous surfaces (SLIPS) are porous nanostructures
impregnated with a low surface tension lubricant. They have recently shown great
promise in various applications that require non-wettable superhydrophobic
surfaces. In this paper, we investigate experimentally the influence of the oil
thickness on the wetting properties and drop impact dynamics of new SLIPS. By
tuning the thickness of the oil layer deposited through spin-coating, we show
that a sufficiently thick layer of oil is necessary to avoid dewetting spots on
the porous nanostructure and thus increasing the homogeneity of the liquid
distribution. Drop impact on these surfaces is investigated with a particular
emphasis on the spreading and rebound dynamics when varying the oil thickness and
the Weber number.
PMID- 29333558
TI - Selective hydrogenation of nitroarenes using an electrogenerated polyoxometalate
redox mediator.
AB - The 2-electron reduced form of the polyoxometalate silicotungstic acid
(H4[SiW12O4]) is shown to be an effective and selective hydrogenation agent for a
range of nitroarenes without the need for any co-catalyst. The ease of generation
of the active species and its recyclability suggest that a new approach to this
important class of chemical conversions is possible.
PMID- 29333560
TI - A design of experiment approach for efficient multi-parametric drug testing using
a Caenorhabditis elegans model.
AB - When studying the drug effectiveness towards a target model, one should
distinguish the effects of the drug itself and of all the other factors that
could influence the screening outcome. This comprehensive knowledge is crucial,
especially when model organisms are used to study the drug effect at a systemic
level, as a higher number of factors can influence the drug-testing outcome.
Covering the entire experimental domain and studying the effect of the
simultaneous change in several factors would require numerous experiments, which
are costly and time-consuming. Therefore, a design of experiment (DoE) approach
in drug-testing is emerging as a robust and efficient method to reduce the use of
resources, while maximizing the knowledge of the process. Here, we used a 3
factor-Doehlert DoE to characterize the concentration-dependent effect of the
drug doxycycline on the development duration of the nematode Caenorhabditis
elegans. To cover the experimental space, 13 experiments were designed and
performed, where different doxycycline concentrations were tested, while also
varying the temperature and the food amount, which are known to influence the
duration of C. elegans development. A microfluidic platform was designed to
isolate and culture C. elegans larvae, while testing the doxycycline effect with
full control of temperature and feeding over the entire development. Our approach
allowed predicting the doxycycline effect on C. elegans development in the
complete drug concentration/temperature/feeding experimental space, maximizing
the understanding of the effect of this antibiotic on the C. elegans development
and paving the way towards a standardized and optimized drug-testing process.
PMID- 29333559
TI - Oxidation of a [Cu2S] complex by N2O and CO2: insights into a role of
tetranuclearity in the CuZ site of nitrous oxide reductase.
AB - Oxidation of a [Cu2(MU-S)] complex by N2O or CO2 generated a [Cu2(MU-SO4)]
product. In the presence of a sulfur trap, a [Cu2(MU-O)] species also formed from
N2O. A [Cu2(MU-CS3)] species derived from CS2 modeled initial reaction
intermediates. These observations indicate that one role of tetranuclearity in
the CuZ catalytic site of nitrous oxide reductase is to protect the crucial S2-
ligand from oxidation.
PMID- 29333561
TI - Pharmacokinetics of the B-Cell Lymphoma 2 (Bcl-2) Inhibitor Venetoclax in Female
Subjects with Systemic Lupus Erythematosus.
AB - BACKGROUND AND OBJECTIVE: Venetoclax is an oral selective Bcl-2 inhibitor
approved for the treatment of patients with chronic lymphocytic leukemia with 17p
deletion. Mechanistic and preclinical evidence warranted evaluation of venetoclax
for the treatment of systemic lupus erythematosus (SLE). This work characterized
the pharmacokinetics of venetoclax in female subjects with SLE. METHODS: Single
(10-500 mg) and multiple (30-600 mg) escalating doses of venetoclax or matching
placebo were evaluated using randomized, double-blind, placebo-controlled designs
(6 active and 2 placebo per dose with 73 unique SLE patients enrolled, 25 of whom
enrolled twice). The multiple-dose evaluation consisted of two cycles, each with
once-daily dosing for 7 days followed by a 21-day washout. Non-compartmental and
population pharmacokinetic analyses of venetoclax serial plasma concentrations
were conducted. RESULTS: Venetoclax exhibited approximately dose-proportional
exposures, with peak concentrations observed 4-8 h post-dose. Venetoclax steady
state exposures were achieved by day 4 of dosing, and the median area under the
plasma concentration-time curve (AUC) accumulation ratio ranged from 1.1 to 1.5.
A two-compartment model with first-order absorption and elimination described
venetoclax pharmacokinetics. The estimates (95% bootstrap confidence interval)
for venetoclax apparent clearance, central and peripheral volumes of
distribution, intercompartmental clearance, absorption rate constant, and lag
time were 16.3 L/h (14.6-17.9), 37 L (26-57), 122 L (98-183), 3.7 L/h (2.6-5.0),
0.13 h-1 (0.11-0.17), and 1.6 h (1.6-1.7), respectively. The population estimate
for venetoclax terminal-phase elimination half-life was approximately 28 h.
CONCLUSIONS: In female subjects with SLE, venetoclax displayed pharmacokinetic
characteristics consistent with previous observations in subjects with
hematologic malignancies. CLINICALTRIALS. GOV IDENTIFIER: NCT01686555.
PMID- 29333562
TI - Have You Ever Googled a Patient or Been Friended by a Patient? Social Media
Intersects the Practice of Genetic Counseling.
AB - Patients and healthcare providers are becoming increasingly connected via social
media, bringing new opportunities and challenges. Direct connection can occur
between patients and providers using online tools such as Facebook and LinkedIn.
In addition, providers can gather information about patients using a search
engine such as Google, referred to as patient-targeted Googling (PTG). An online
54-item survey was used to gain information on (1) how and to what extent genetic
counseling students and genetic counselors connect directly with patients via
social media sites, and (2) gather information on providers using PTG. Four
hundred genetic counseling students and genetic counselors participated in the
survey. The majority of respondents (88.9%; n = 344/387) find it is never or
rarely acceptable to interact with current patients via social media sites;
however, 27.7% (n = 110/397) have visited a patient's social media site.
Gathering information for patient care was the most commonly reported reason
(76.8%; n = 43/56). Thirty-three percent (n = 130/394) have considered searching
online or actually searched online for information about a patient. Curiosity was
the most common reason (92.7%; n = 114/123); although, respondents also used PTG
to obtain contact information and to prepare for patient sessions. Our study
supports the need for development and dissemination of professional guidelines to
serve as a valuable resource for practicing genetic counselors and genetic
counseling training programs.
PMID- 29333563
TI - Aldehyde Dehydrogenase Activity in Adipose Tissue: Isolation and Gene Expression
Profile of Distinct Sub-population of Mesenchymal Stromal Cells.
AB - Thanks to their relative abundance and easier collection, adipose tissue (AT) is
considered an alternative source for the isolation of mesenchymal stromal cells
(MSCs). MSCs have great therapeutic values and are thus under investigations for
several clinical indications such as regenerative medicine and immunomodulation.
In this work, we aimed to identify, isolate and characterize AT-MSCs based on
their aldehyde dehydrogenase (ALDH) activity known to be a classical feature of
stem cells. FACS technology allowed to isolate two different populations of AT
MSCs according to their ALDH activity (referred as ALDH+ and ALDH-). Depending on
their ALDH activity, the transcriptome analysis of both cell populations
demonstrated a differential pattern of genes related to the main properties of
MSCs (proliferation, response to hypoxia, angiogenesis, phenotype, stemness,
multilineage, hematopoiesis, immunomodulation). Based on these profiling, both AT
MSC populations could differ in terms of biological responses and
functionalities. Collectively, the use of ALDH for isolating and identifying sub
populations of MSCs with specific gene profile may represent an alternative
method to provide solutions for targeted therapeutic applications.
PMID- 29333564
TI - Is 123I-metaiodobenzylguanidine heart-to-mediastinum ratio dependent on age? From
Japanese Society of Nuclear Medicine normal database.
AB - BACKGROUND: Heart-to-mediastinum ratios (HMRs) of 123I-metaiodobenzylguanidine
(MIBG) have usually been applied to prognostic evaluations of heart failure and
Lewy body disease. However, whether these ratios depend on patient age has not
yet been clarified using normal databases. METHODS: We analyzed 62 patients
(average age 57 +/- 19 years, male 45%) derived from a normal database of the
Japanese Society of Nuclear Medicine working group. The HMR was calculated from
early (15 min) and delayed (3-4 h) anterior planar 123I-MIBG images. All HMRs
were standardized to medium-energy general purpose (MEGP) collimator equivalent
conditions using conversion coefficients for the collimator types. Washout rates
(WR) were also calculated, and we analyzed whether early and late HMR, and WR are
associated with age. RESULTS: Before standardization of HMR to MEGP collimator
conditions, HMR and age did not significantly correlate. However, late HMR
significantly correlated with age after standardization: late HMR = - 0.0071 *
age + 3.69 (r2 = 0.078, p = 0.028), indicating that a 14-year increase in age
corresponded to a decrease in HMR of 0.1. Whereas the lower limit (2.5% quantile)
of late HMR was 2.3 for all patients, it was 2.5 and 2.0 for those aged <= 63 and
> 63 years, respectively. Early HMR tended to be lower in subjects with the
higher age (p = 0.076), whereas WR was not affected by age. CONCLUSION: While
late HMR was slightly decreased in elderly patients, the lower limit of 2.2-2.3
can still be used to determine both early and late HMR.
PMID- 29333566
TI - Principles of Management of Central Nervous System Infections.
AB - CNS infections in children are medical emergency and are associated with high
mortality and morbidity. For diagnosis, a high index of suspicion is required.
Clinical assessment should be supplemented by laboratory investigations including
CSF Gram stain and cultures, blood culture, PCR on CSF, serological tests, and
imaging. Commonly associated life threatening complications include coma,
seizure, raised intracranial pressure (ICP), focal deficits, shock, respiratory
failure, and fluid and electrolyte abnormalities. Immediate management should
first address control of airway, breathing and circulation; protocolized
management of raised ICP and status epilepticus; maintaining adequate
intravascular volume; and close monitoring for early detection of complications.
Appropriate antimicrobial agents should be administered promptly according to the
suspected pathogen. Clinical evaluation, laboratory workup, specific
antimicrobial therapy, supportive treatment, and management of associated
complications should go hand in hand in a protocolized way for better outcome.
PMID- 29333565
TI - Manual on the proper use of lutetium-177-labeled somatostatin analogue (Lu-177
DOTA-TATE) injectable in radionuclide therapy (2nd ed.).
AB - Here we present the guideline for the treatment of neuroendocrine tumors using Lu
177-DOTA-TATE on the basis of radiation safety aspects in Japan. This guideline
was prepared by a study supported by Ministry of Health, Labour, and Welfare, and
approved by Japanese Society of Nuclear Medicine. Lu-177-DOTA-TATE treatment in
Japan should be carried out according to this guideline. Although this guideline
is applied in Japan, the issues for radiation protection shown in this guideline
are considered internationally useful as well. Only the original Japanese version
is the formal document.
PMID- 29333567
TI - Predictors for Intracranial Hemorrhage Following Intravenous Thrombolysis in
Posterior Circulation Stroke.
AB - Intravenous thrombolysis (IVT) is a standard treatment for anterior (ACS) and
posterior circulation stroke (PCS). However, due to the low occurrence of PCS and
of intracranial hemorrhage (ICH) in PCS, the knowledge about ICH predictors
following IVT in PCS is sparse. Our aim was to identify predictors for ICH
following IVT in PCS. The set consisted of 1281 consecutive ischemic stroke (IS)
patients treated with IVT, out of which 158 (103 males; mean age 65.6 +/- 12.3
years) had PCS. Collected data include baseline characteristics, common stroke
risk factors, pre-medication, stroke severity, admission blood glucose level,
blood pressure and treatment with intravenous antihypertensive therapy before and
during IVT, occlusion of arteries, recanalization rate, time to treatment, and
clinical outcome at day 90. Overall, 11 (7%) patients had ICH. Atrial
fibrillation (p = 0.004), neurological deficit at time of treatment in the
National Institutes of Health Stroke Scale (p = 0.016), decreased level of
consciousness (p = 0.003), occlusion of basilar artery (p = 0.007), occlusion of
PCA (p = 0.001), and additional endovascular therapy (p = 0.001) were identified
by logistic regression analysis as significant predictors for ICH in PCS.
Patients with ischemic lesion in the brainstem, occlusion of vertebral artery, or
absence of basilar and posterior cerebral artery occlusion might be considered
for treatment with IVT even in borderline cases. Those patients seem to have less
frequently favorable outcomes without an increase in ICH rate. Time to IVT in PCS
seems not to influence ICH risk or chances for favorable outcomes as
significantly as it does in ACS.
PMID- 29333569
TI - An integrated fuzzy-based advanced eutrophication simulation model to develop the
best management scenarios for a river basin.
AB - Assessment of water quality status of a river with respect to its discharge has
become prerequisite to sustainable river basin management. The present paper
develops an integrated model for simulating and evaluating strategies for water
quality management in a river basin management by controlling point source
pollutant loadings and operations of multi-purpose projects. Water Quality
Analysis and Simulation Program (WASP version 8.0) has been used for modeling the
transport of pollutant loadings and their impact on water quality in the river.
The study presents a novel approach of integrating fuzzy set theory with an
"advanced eutrophication" model to simulate the transmission and distribution of
several interrelated water quality variables and their bio-physiochemical
processes in an effective manner in the Ganges river basin, India. After
calibration, simulated values are compared with the observed values to validate
the model's robustness. Fuzzy technique of order preference by similarity to
ideal solution (F-TOPSIS) has been used to incorporate the uncertainty associated
with the water quality simulation results. The model also simulates five
different scenarios for pollution reduction, to determine the maximum pollutant
loadings during monsoon and dry periods. The final results clearly indicate how
modeled reduction in the rate of wastewater discharge has reduced impacts of
pollutants in the downstream. Scenarios suggesting a river discharge rate of 1500
m3/s during the lean period, in addition to 25 and 50% reduction in the load
rate, are found to be the most effective option to restore quality of river
Ganges. Thus, the model serves as an important hydrologic tool to the policy
makers by suggesting appropriate remediation action plans.
PMID- 29333568
TI - Comparison of effects of thawing entire donor sperm vial vs. partial thawing
(shaving) on sperm quality.
AB - PURPOSE: Partial thawing of a vial of cryopreserved sperm (shaving) is sometimes
applied as a measure to preserve sperm for further use, particularly in cases of
very restricted sperm quantity. However, mechanical violence may disrupt the
sperm-wall and lead to impaired in-vitro fertilization (IVF) outcomes. MATERIAL
AND METHODS: In a retrospective case-control study at a tertiary, university
affiliated medical center, we compared the IVF/intracytoplasmic sperm injection
(ICSI) outcomes of patients who used donor sperm following partial thawing
(shaving) of the vial of cryopreserved sperm (n = 99) to a control group
consisting of patients for whom the vial of sperm was completely thawed before
use (n = 99). RESULTS: While no differences were observed in the rates of oocyte
fertilization, the mean number of top-quality embryos (TQE) was significantly
lower in the shaving group than in the complete thawing group (1.33 +/- 0.17 vs.
1.87 +/- 0.17, p < 0.02). Experimental analysis of aliquots from the same donors
revealed significantly reduced motility in sperm samples that were shaved vs.
fully thawed (6.5 vs. 37.1%, p < 0.001). CONCLUSIONS: In cases in which available
cryopreserved sperm samples are limited, shaving of the vial without thawing can
be used but with caution and only when absolutely necessary. Further, large
prospective studies are needed to better clarify whether there is post-thawing
sperm damage and to compare IVF outcomes after these two thawing methods.
PMID- 29333570
TI - Professional quality of life, wellness education, and coping strategies among
emergency physicians.
AB - Professional quality of life (ProQOL) is affected by and affects professional
well-being and performance. The objectives of this study are to identify risk
factors of ProQOL among EM physicians in Zagazig University hospitals (ZUHs), to
detect the relationship between ProQOL and coping strategies, and to measure the
implication of the Worksite Wellness Education (WWE) program on improving
knowledge skills, ProQOL, and coping. An intervention study was conducted among
108 EM physicians at ZUHs through two stages: assessing ProQOL subscales (CS, BO,
and STS) and coping strategies and conducting the WWE program. A pre-post-test
design was used in the evaluation. CS was higher among the older age group,
smokers, nighttime sleepers, and hobbies' practitioners. Coping strategies
carried out by EM physicians to overcome stress and their ProQOL scores were
improved significantly post program. ProQOL has multiple factors that affect it.
Applying the WWE program will address this concept and may raise awareness about
how to cope with work stressors.
PMID- 29333571
TI - Diurnal variations in personal care products in seawater and mussels at three
Mediterranean coastal sites.
AB - The presence of personal care products (PCPs) in the marine environment is of
major concern. PCPs, UV filters, and musks can enter the marine environment
indirectly through wastewater or directly via recreational activities. We
conducted this study to document patterns in the occurrence of seven PCPs at
three coastal sites impacted by recreational activities during 1 day. The study
focused on diurnal variations in these seven PCPs in seawater and indigenous
mussels. In seawater, UV filters showed diurnal variations that mirrored
variations in recreational activities at the sites. Ethylhexyl methoxycinnamate
(EHMC) and octocrylene (OC) water concentrations increased from under the limit
of quantification in the morning to 106 and 369 ng/L, respectively, when
recreational activities were the highest. In mussels, diurnal variations in OC
were observed, with the lowest concentrations recorded in the morning and then
increasing throughout the day. As Mytilus spp. are widely used as sentinels in
coastal pollution monitoring programs (mussel watch), our findings on diurnal
variations could enhance sampling recommendations for recreational sites impacted
by PCPs.
PMID- 29333572
TI - Possible protective effect of the algae spirulina against nephrotoxicity induced
by cyclosporine A and/or gamma radiation in rats.
AB - The present study was conducted to evaluate the possible protective role of the
algae spirulina (Sp) against nephrotoxicity and oxidative stress which are the
main secondary effects induced by the immunosuppressant drug CSA and/or ionizing
radiation. In this study, male rats were given Sp (1 g/kg) either for 15 days
before irradiation (6.5 Gy) or 5 days before and 10 days concomitant with CSA (25
mg/kg). Markers used to assess renal injury included serum creatinine, urea,
glucose, albumin, protein, and lipid profile as well as kidney content of reduced
glutathione (GSH); lipid peroxidation (thiobarbituric acid reactive substances
(TBARS)); nitrite and superoxide dismutase (SOD) activity. In addition, some
trace elements (Zn and Mg) were estimated in kidney. Apoptosis was assessed by
immunohistochemical estimation of caspase-3 expression in addition to
histopathological examination. Results revealed that gamma radiation and/or CSA
induced elevation in urea, creatinine, lipids, and glucose while decreasing
albumin and protein levels. There was a noticeable increase in kidney content of
GSH, TBARS, and nitrite. Meanwhile, profound decrease in kidney SOD activity was
observed. Treatment with Sp significantly reversed the changes induced by CSA
and/or gamma radiation in renal function tests. Spirulina also ameliorated kidney
oxidative stress through decreasing GSH, TBARS, and nitrite kidney content while
increasing SOD activity. Histopathological examination further confirmed Sp
protective efficacy. Moreover, kidney caspase-3 expression that was triggered by
CSA and/or gamma radiation was decreased. In conclusion, spirulina can be
regarded as a promising renoprotective natural agent against renal injury induced
by CSA and/or gamma radiation.
PMID- 29333573
TI - Simultaneous site-directed mutagenesis of duplicated loci in soybean using a
single guide RNA.
AB - KEY MESSAGE: Using a gRNA and Agrobacterium-mediated transformation, we performed
simultaneous site-directed mutagenesis of two GmPPD loci in soybean. Mutations in
GmPPD loci were confirmed in at least 33% of T2 seeds. The clustered regularly
interspaced short palindromic repeat (CRISPR)/CRISPR-associated endonuclease 9
(Cas9) system is a powerful tool for site-directed mutagenesis in crops. Using a
single guide RNA (gRNA) and Agrobacterium-mediated transformation, we performed
simultaneous site-directed mutagenesis of two homoeologous loci in soybean
(Glycine max), GmPPD1 and GmPPD2, which encode the orthologs of Arabidopsis
thaliana PEAPOD (PPD). Most of the T1 plants had heterozygous and/or chimeric
mutations for the targeted loci. The sequencing analysis of T1 and T2 generations
indicates that putative mutation induced in the T0 plant is transmitted to the T1
generation. The inheritable mutation induced in the T1 plant was also detected.
This result indicates that continuous induction of mutations during T1 plant
development increases the occurrence of mutations in germ cells, which ensures
the transmission of mutations to the next generation. Simultaneous site-directed
mutagenesis in both GmPPD loci was confirmed in at least 33% of T2 seeds
examined. Approximately 19% of double mutants did not contain the Cas9/gRNA
expression construct. Double mutants with frameshift mutations in both GmPPD1 and
GmPPD2 had dome-shaped trifoliate leaves, extremely twisted pods, and produced
few seeds. Taken together, our data indicate that continuous induction of
mutations in the whole plant and advancing generations of transgenic plants
enable efficient simultaneous site-directed mutagenesis in duplicated loci in
soybean.
PMID- 29333574
TI - Unique metabolic activation of adipose tissue macrophages in obesity promotes
inflammatory responses.
AB - AIMS/HYPOTHESIS: Recent studies have identified intracellular metabolism as a
fundamental determinant of macrophage function. In obesity, proinflammatory
macrophages accumulate in adipose tissue and trigger chronic low-grade
inflammation, that promotes the development of systemic insulin resistance, yet
changes in their intracellular energy metabolism are currently unknown. We
therefore set out to study metabolic signatures of adipose tissue macrophages
(ATMs) in lean and obese conditions. METHODS: F4/80-positive ATMs were isolated
from obese vs lean mice. High-fat feeding of wild-type mice and myeloid-specific
Hif1alpha-/- mice was used to examine the role of hypoxia-inducible factor-1alpha
(HIF-1alpha) in ATMs part of obese adipose tissue. In vitro, bone marrow-derived
macrophages were co-cultured with adipose tissue explants to examine adipose
tissue-induced changes in macrophage phenotypes. Transcriptome analysis, real
time flux measurements, ELISA and several other approaches were used to determine
the metabolic signatures and inflammatory status of macrophages. In addition,
various metabolic routes were inhibited to determine their relevance for cytokine
production. RESULTS: Transcriptome analysis and extracellular flux measurements
of mouse ATMs revealed unique metabolic rewiring in obesity characterised by both
increased glycolysis and oxidative phosphorylation. Similar metabolic activation
of CD14+ cells in obese individuals was associated with diabetes outcome. These
changes were not observed in peritoneal macrophages from obese vs lean mice and
did not resemble metabolic rewiring in M1-primed macrophages. Instead, metabolic
activation of macrophages was dose-dependently induced by a set of adipose tissue
derived factors that could not be reduced to leptin or lactate. Using metabolic
inhibitors, we identified various metabolic routes, including fatty acid
oxidation, glycolysis and glutaminolysis, that contributed to cytokine release by
ATMs in lean adipose tissue. Glycolysis appeared to be the main contributor to
the proinflammatory trait of macrophages in obese adipose tissue. HIF-1alpha, a
key regulator of glycolysis, nonetheless appeared to play no critical role in
proinflammatory activation of ATMs during early stages of obesity.
CONCLUSIONS/INTERPRETATION: Our results reveal unique metabolic activation of
ATMs in obesity that promotes inflammatory cytokine release. Further
understanding of metabolic programming in ATMs will most likely lead to novel
therapeutic targets to curtail inflammatory responses in obesity. DATA
AVAILABILITY: Microarray data of ATMs isolated from obese or lean mice have been
submitted to the Gene Expression Omnibus (accession no. GSE84000).
PMID- 29333575
TI - A phase 1, dose-escalation study of PF-06664178, an anti-Trop-2/Aur0101 antibody
drug conjugate in patients with advanced or metastatic solid tumors.
AB - Purpose and Methods Trop-2 is a glycoprotein over-expressed in many solid tumors
but at low levels in normal human tissue, providing a potential therapeutic
target. We conducted a phase 1 dose-finding study of PF-06664178, an antibody
drug conjugate that targets Trop-2 for the selective delivery of the cytotoxic
payload Aur0101. The primary objective was to determine the maximum tolerated
dose and recommended phase 2 dose. Secondary objectives included further
characterization of the safety profile, pharmacokinetics and antitumor activity.
Eligible patients were enrolled and received multiple escalating doses of PF
06664178 in an open-label and unblinded manner based on a modified continual
reassessment method. Results Thirty-one patients with advanced or metastatic
solid tumors were treated with escalating doses of PF-06664178 given
intravenously every 21 days. Doses explored ranged from 0.15 mg/kg to 4.8 mg/kg.
Seven patients experienced at least one dose limiting toxicity (DLT), either
neutropenia or rash. Doses of 3.60 mg/kg, 4.2 mg/kg and 4.8 mg/kg were considered
intolerable due to DLTs in skin rash, mucosa and neutropenia. Best overall
response was stable disease in 11 patients (37.9%). None of the patients had a
partial or complete response. Systemic exposure of PF-06664178 increased in a
dose-related manner. Serum concentrations of free Aur0101 were substantially
lower than those of PF-06664178 and total antibody. No correlation of Trop-2
expression and objective response was observed, although Trop-2 overexpression
was not required for study entry. The intermediate dose of 2.4 mg/kg appeared to
be the highest tolerated dose, but this was not fully explored as the study was
terminated early due to excess toxicity. Conclusion PF-06664178 showed toxicity
at high dose levels with modest antitumor activity. Neutropenia, skin rash and
mucosal inflammation were dose limiting toxicities. Findings from this study may
potentially aid in future antibody drug conjugate design and trials.
PMID- 29333576
TI - Bone radionuclide therapy and increased survival with radium-223 is the way to go
for nuclear medicine: the offer that oncologists cannot refuse.
PMID- 29333577
TI - Prostate Cancer Patients' Understanding of the Gleason Scoring System:
Implications for Shared Decision-Making.
AB - The Gleason scoring system is a key component of a prostate cancer diagnosis,
since it indicates disease aggressiveness. It also serves as a risk communication
tool that facilitates shared treatment decision-making. However, the system is
highly complex and therefore difficult to communicate: factors which have been
shown to undermine well-informed and high-quality shared treatment decision
making. To systematically explore prostate cancer patients' understanding of the
Gleason scoring system (GSS), we assessed knowledge and perceived importance
among men who had completed treatment (N = 50). Patients were administered a
survey that assessed patient knowledge and patients' perceived importance of the
GSS, as well as demographics, medical factors (e.g., Gleason score at diagnosis),
and health literacy. Bivariate analyses were conducted to identify associations
with patient knowledge and perceived importance of the GSS. The sample was
generally well-educated (48% with a bachelor's degree or higher) and health
literate (M = 12.9, SD = 2.2, range = 3-15). Despite this, patient knowledge of
the GSS was low (M = 1.8, SD = 1.4, range = 1-4). Patients' understanding of the
importance of the GSS was moderate (M = 2.8, SD = 1.0, range = 0-4) and was
positively associated with GSS knowledge (p < .01). Additionally, GSS knowledge
was negatively associated with years since biopsy (p < .05). Age and health
literacy were positively associated with patients' perceived importance of the
GSS (p < .05), but not with GSS knowledge. Patient knowledge is thus less than
optimal and would benefit from enhanced communication to maximize shared
treatment decision-making. Future studies are needed to explore the potential
utility of a simplified Gleason grading system and improved patient-provider
communication.
PMID- 29333578
TI - Insulin resistance and bone: a biological partnership.
AB - Despite a clear association between type 2 diabetes (T2D) and fracture risk, the
pathogenesis of bone fragility in T2D has not been clearly elucidated. Insulin
resistance is the primary defect in T2D. Insulin signalling regulates both bone
formation and bone resorption, but whether insulin resistance can affect bone has
not been established. On the other hand, evidence exists that bone might play a
role in the regulation of glucose metabolism. This article reviews the available
experimental and clinical evidence on the interplay between bone and insulin
resistance. Interestingly, a bilateral relationship between bone and insulin
resistance seems to exist that unites them in a biological partnership.
PMID- 29333580
TI - Persistent Organochlorine Contaminant Residues in Tissues of Hedgehogs from
Turkey.
AB - The residues of persistent organochlorinated pollutants (POPs), namely
polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) (HCHs,
CHLs, HCCPs, DDTs, and dicofol congeners) were investigated in the hair and
muscle of road-killed Erinaceus roumanicus and E. concolor in Turkey. Mean
residue levels were as follows: in hair, PCBs = 7.43 +/- 4.88 ng/g and OCPs =
9.21 +/- 1.27 ng/g; in muscle, PCBs = 30.73 +/- 2.51 ng/g and OCPs = 145.04 +/-
16.59 ng/g. There was no significant difference between species and sex, while
there was significant difference between habitats and regions in terms of either
total PCB and OCP levels, or POP levels (p < 0.05). Age was a determinative
factor for the bio-accumulation of POPs. The contaminant levels were high in the
species, sample areas, and habitats. The data also showed that tissues of
hedgehogs are suitable for monitoring and evaluating the bioaccumulation of POP
levels in Turkey.
PMID- 29333579
TI - Factors associated with the number and size of renal angiomyolipomas in sporadic
angiomyolipoma (sAML): a study of adult patients with sAML managed in a Dutch
tertiary referral center.
AB - PURPOSE: To describe the patient characteristics, treatments, disease monitoring,
and kidney function of patients with sporadic angiomyolipoma (sAML), stratified
by the number and size of renal angiomyolipomas (AMLs). METHODS: Single-center
retrospective analysis of patients with sAML treated from 1990 to 2015 in a
dedicated clinic for inheritable tumor syndromes in a tertiary referral center
from the Netherlands. Patients' first AML assessment at the clinic was defined as
the index date. Patient characteristics were measured at the index date.
Treatments, disease monitoring, and kidney function were measured post-index
date. RESULTS: The study sample included 53 patients followed for a total of
184.6 patient-years. At the index date, the largest AML was >= 3.5 cm for 26
patients and < 3.5 cm for 27 patients (including six patients with five or more
AMLs of < 3.5 cm). As compared to patients with AMLs < 3.5 cm, patients with
largest AML >= 3.5 cm had higher frequency of pre-index bleeding episodes (31 vs.
4%), pre-index hypertension (35 vs. 15%), post-index nephrectomy (19 vs. 4%),
post-index embolization (8 vs. 0%), and post-index renal scans (1.14 vs. 0.74
scans/year). Kidney impairment was especially pronounced in young adults with AML
>= 3.5 cm. On average, patients with sAML developed chronic kidney disease stage
two earlier than the general Dutch population (age 42 vs. 55 years), but later
than the patients with tuberous sclerosis complex (35 years). CONCLUSIONS:
Patients with sAML, especially those with larger AMLs, have high disease burden.
PMID- 29333581
TI - High final energy of gallium arsenide laser increases MyoD gene expression during
the intermediate phase of muscle regeneration after cryoinjury in rats.
AB - The aim of this study was to determine the effects of gallium arsenide (GaAs)
laser on IGF-I, MyoD, MAFbx, and TNF-alpha gene expression during the
intermediate phase of muscle regeneration after cryoinjury 21 Wistar rats were
divided into three groups (n = 7 per group): untreated with no injury (control
group), cryoinjury without GaAs (injured group), and cryoinjury with GaAs (GaAs
injured group). The cryoinjury was induced in the central region of the tibialis
anterior muscle (TA). The region injured was irradiated once a day during 14 days
using GaAs laser (904 nm; spot size 0.035 cm2, output power 50 mW; energy density
69 J cm-2; exposure time 4 s per point; final energy 4.8 J). Twenty-four hours
after the last application, the right and left TA muscles were collected for
histological (collagen content) and molecular (gene expression of IGF-I, MyoD,
MAFbx, and TNF-alpha) analyses, respectively. Data were analyzed using one-way
ANOVA at P < 0.05. There were no significant (P > 0.05) differences in collagen
density and IGF-I gene expression in all experimental groups. There were similar
(P < 0.05) decreases in MAFbx and TNF-alpha gene expression in the injured and
GaAs-injured groups, compared to control group. The MyoD gene expression
increased (P = 0.008) in the GaAs-injured group, but not in the injured group (P
= 0.338), compared to control group. GaAs laser therapy had a positive effect on
MyoD gene expression, but not IGF-I, MAFbx, and TNF-alpha, during intermediary
phases (14 days post-injury) of muscle repair.
PMID- 29333582
TI - Outpatient erbium:YAG (2940 nm) laser treatment for snoring: a prospective study
on 40 patients.
AB - Snoring is a sleep phenomenon due to the partial upper airway obstruction during
sleep which causes vibration of the tissues of the rhino-oro-hypopharynx and less
frequently the larynx. This study evaluated the use and effectiveness of the
erbium:YAG 2940-nm laser as an adjunctive in providing treatment for patients
suffering from chronic snoring-related sleep disorders. A prospective study of 40
consecutive patients with snoring and sleep disorders was performed, assessing
data before and after three Er:YAG laser treatment sessions. During laser
treatment, the pain was almost absent. There were no side effects, except a very
mild sore throat in 1 out of 40 patients. The patient's evaluation of
satisfaction of the results obtained after the treatments showed that 85% of
cases were very satisfied, 5 patients (12.5%) reported being fairly satisfied
with the treatment and only 1 subject (2.5%) was not satisfied. Mallampati,
Friedman Tongue Position, and degree of O (oropharynx) at nose oropharynx
hypopharynx and larynx classification were significantly decreased after the
laser sessions. The decrease of Epworth Sleepiness Scale and Visual Analogue
Scale for loudness of snoring, waking up during sleep because of snoring, dry
mouth on waking, and choking was all statistically significant. The incidence of
dreaming during the night also raised significantly; 30/40 (75%) of cases
perceived less tightness in their throat and better breathing after treatment.
These results were stable at 20 months follow-up (14-24 q) in 72% of cases.
Nonsurgical and non-invasive Er:YAG laser treatment demonstrated to be a valid
procedure in reducing the loudness of snoring.
PMID- 29333583
TI - The Microbial Community of Tardigrades: Environmental Influence and Species
Specificity of Microbiome Structure and Composition.
AB - Symbiotic associations of metazoans with bacteria strongly influence animal
biology since bacteria are ubiquitous and virtually no animal is completely free
from them. Tardigrades are micrometazoans famous for their ability to undergo
ametabolic states (cryptobiosis) but very little information is available on
potential microbial associations. We characterized the microbiomes of six
limnoterrestrial tardigrade species belonging to several phylogenetic lines in
tandem with the microbiomes of their respective substrates. The experimental
design enabled us to determine the effects of both the environment and the host
genetic background on the tardigrade microbiome; we were able to define the
microbial community of the same species sampled from different environments, and
the communities of different species from the same environment. Our 16S rRNA gene
amplicon approach indicated that the tardigrade microbiome is species-specific
and well differentiated from the environment. Tardigrade species showed a much
lower microbial diversity compared to their substrates, with only one significant
exception. Forty-nine common OTUs (operational taxonomic units) were classified
into six bacterial phyla, while four common OTUs were unclassified and probably
represent novel bacterial taxa. Specifically, the tardigrade microbiome appears
dominated by Proteobacteria and Bacteroidetes. Some OTUs were shared between
different species from geographically distant samples, suggesting the associated
bacteria may be widespread. Putative endosymbionts of tardigrades from the order
Rickettsiales were identified. Our results indicated that like all other animals,
tardigrades have their own microbiota that is different among species, and its
assembly is determined by host genotype and environmental influences.
PMID- 29333585
TI - Indian Journal of Gastroenterology: The promises fulfilled and waiting for
fulfillment!
PMID- 29333584
TI - In focus in HCB.
PMID- 29333586
TI - Pre-operative templating for knee arthroplasty shows low accuracy with standard X
rays.
AB - OBJECTIVES: The purpose of this study was to evaluate the accuracy and
reliability of pre-operative templating in predicting the size of femoral and
tibial components and the effect of coronal deformity on templating accuracy.
METHODS: This was a retrospective study of 39 pre-operative templates prepared by
three different surgeons with different levels of training. The accuracy and
reliability measures were evaluated by alpha and kappa coefficients of agreement.
The analysis of the effect of coronal deformity on the accuracy of the template
was measured by the Spearman's correlation test. RESULTS: Templating was accurate
for the femoral component in 28.21% of anterposterior (AP) radiographs and 35.90%
of lateral radiographs. Kappa coefficients were respectively 0.111 (95%
confidence interval [95%CI]: -0.19 to 0.241) and 0.200 (95%CI: -0.010 to 0.401),
indicating poor agreement. Templating accuracy for the tibial component were,
respectively, 37.61% and 47.01% for AP and lateral views. Kappa coefficients were
0.186 (95%CI: -0.070 to 0.379) for the AP view and 0.315 (95%CI: -0.199 to 0.431)
for the lateral view, showing poor and slight agreement respectively. Considering
a margin of error of +/-1 sizes, the agreement level improved for all components,
particularly for tibia, where agreement levels become very good. The inter
observer agreement was fair for all components, except for the lateral view of
the femoral component, whose agreement was good. The Spearman correlation test
showed no correlation between accuracy of templating and coronal deformity.
CONCLUSION: Pre-operative templating is an unreliable and inaccurate tool. There
is no relation between coronal deformity and accuracy of templating.
PMID- 29333587
TI - Genetic characterization and modification of a bioethanol-producing yeast strain.
AB - Yeast Saccharomyces cerevisiae strains isolated from different sources generally
show extensive genetic and phenotypic diversity. Understanding how genomic
variations influence phenotypes is important for developing strategies with
improved economic traits. The diploid S. cerevisiae strain NY1308 is used for
cellulosic bioethanol production. Whole genome sequencing identified an extensive
amount of single nucleotide variations and small insertions/deletions in the
genome of NY1308 compared with the S288c genome. Gene annotation of the assembled
NY1308 genome showed that 43 unique genes are absent in the S288c genome.
Phylogenetic analysis suggested most of the unique genes were obtained through
horizontal gene transfer from other species. RNA-Seq revealed that some unique
genes were not functional in NY1308 due to unidentified intron sequences. During
bioethanol fermentation, NY1308 tends to flocculate when certain inhibitors
(derived from the pretreatment of cellulosic feedstock) are present in the
fermentation medium. qRT-PCR and genetic manipulation confirmed that the novel
gene, NYn43, contributed to the flocculation ability of NY1308. Deletion of NYn43
resulted in a faster fermentation rate for NY1308. This work disclosed the
genetic characterization of a bioethanol-producing S. cerevisiae strain and
provided a useful paradigm showing how the genetic diversity of the yeast
population would facilitate the personalized development of desirable traits.
PMID- 29333589
TI - New species and new record of the genus Cheloniodiplostomum (Trematoda,
Proterodiplostomidae, Polycotylinae), parasites of freshwater turtles from
Argentina.
AB - The aim of the present paper is to describe a new species of the genus
Cheloniodiplostomum (Digenea, Proterodiplostomidae) in the Hilaire's toadhead
turtle Phrynops hilarii from Argentina and to expand the geographic and host
distribution of Cheloniodiplostomum testudinis. Additionally, we present a
diagnostic key for Cheloniodiplostomum.
PMID- 29333588
TI - Nitrogen-fixation activity and the abundance and taxonomy of nifH genes in
agricultural, pristine, and urban prairie stream sediments chronically exposed to
different levels of nitrogen loading.
AB - Small streams exert great influences on the retention and attenuation of nitrogen
(N) within stream networks. Human land use can lead to increased transport of
dissolved inorganic N compounds and downstream eutrophication. Microbial activity
in streams is important for maintaining an actively functioning N cycle.
Chronically high N loading in streams affects the rates of the central processes
of the N cycle by increasing rates of nitrification and denitrification, with
biota exhibiting decreased efficiency of N use. The LINXII project measured N
cycle parameters in small streams using 15NO3- tracer release experiments. We
concurrently measured N2 fixation rates in six streams of three types
(agricultural, pristine, and urban prairie streams) as part of this broader study
of major N-cycle processes. Nitrogen fixation in streams was significantly
negatively correlated with nitrate levels, dissolved inorganic N levels, and
denitrification rates. Algal mat and leaf litter samples generally exhibited the
highest rates of N2 fixation. The abundance of nifH genes, as measured by real
time PCR, was marginally correlated with N2-fixation rates, but not to other N
cycle processes or stream characteristics. The nifH sequences observed were
assigned to cyanobacteria, Deltaproteobacteria, Methylococcus, and Rhizobia.
Seasonal changes, disturbances, and varying inputs may encourage a diverse,
flexible, stable N2-fixing guild. Patchiness in the streams should be considered
when assessing the overall impact of N2 fixation, since algal biomass exhibited
high rates of N2 fixation.
PMID- 29333590
TI - Advantages and Disadvantages in Image Processing with Free Software in Radiology.
AB - Currently, there are sophisticated applications that make it possible to
visualize medical images and even to manipulate them. These software applications
are of great interest, both from a teaching and a radiological perspective. In
addition, some of these applications are known as Free Open Source Software
because they are free and the source code is freely available, and therefore it
can be easily obtained even on personal computers. Two examples of free open
source software are Osirix Lite(r) and 3D Slicer(r). However, this last group of
free applications have limitations in its use. For the radiological field,
manipulating and post-processing images is increasingly important. Consequently,
sophisticated computing tools that combine software and hardware to process
medical images are needed. In radiology, graphic workstations allow their users
to process, review, analyse, communicate and exchange multidimensional digital
images acquired with different image-capturing radiological devices. These
radiological devices are basically CT (Computerised Tomography), MRI (Magnetic
Resonance Imaging), PET (Positron Emission Tomography), etc. Nevertheless, the
programs included in these workstations have a high cost which always depends on
the software provider and is always subject to its norms and requirements. With
this study, we aim to present the advantages and disadvantages of these
radiological image visualization systems in the advanced management of
radiological studies. We will compare the features of the VITREA2(r) and AW
VolumeShare 5(r) radiology workstation with free open source software
applications like OsiriX(r) and 3D Slicer(r), with examples from specific
studies.
PMID- 29333592
TI - 3D Models of Female Pelvis Structures Reconstructed and Represented in
Combination with Anatomical and Radiological Sections.
AB - We present a computer program designed to visualize and interact with three
dimensional models of the main anatomical structures of the female pelvis. They
are reconstructed from serial sections of corpse, from the Visible Human project
of the Medical Library of the United States and from serial sections of high
resolution magnetic resonance. It is possible to represent these three
dimensional structures in any spatial orientation, together with sectional images
of corpse and magnetic resonance imaging, in the three planes of space (axial,
coronal and sagittal) that facilitates the anatomical understanding and the
identification of the set of visceral structures of this body region. Actually,
there are few studies that analysze in detail the radiological anatomy of the
female pelvis using three-dimensional models together with sectional images,
making use of open applications for the representation of virtual scenes on low
cost Windows(r) platforms. Our technological development allows the observation
of the main female pelvis viscera in three dimensions with a very intuitive
graphic interface. This computer application represents an important training
tool for both medical students and specialists in gynecology and as a preliminary
step in the planning of pelvic floor surgery.
PMID- 29333593
TI - Control of anterior segment using an antero-posterior lingual sliding retraction
system: a preliminary cone-beam CT study.
AB - BACKGROUND: This study was performed to evaluate the treatment effects of the
antero-posterior lingual retractor (APLR), focusing on the 3-dimensional (3D)
tooth movement of the maxillary anterior teeth and their alveolar bone levels.
METHODS: En masse retraction was performed using either the C-lingual retractor
(CLR, C-group, n = 9) or the antero-posterior lingual retractor (APLR, AP-group,
n = 8). We evaluated 3D movement of the maxillary anterior teeth and alveolar
bone levels, root length of the central incisors, long axes of the maxillary
canines, and occlusal plane changes from CBCT images. RESULTS: After retraction,
the central incisors were more significantly intruded and their root apex was
more retracted in the AP-group. The long axis of the canine was well maintained
in the AP-group. There were no differences in the steepness of occlusal plane and
the incidence of alveolar bone loss or of root resorption during en masse
retraction with the two retractors. CONCLUSIONS: The clockwise bowing effect of
the anterior segment was less with the APLR, which prevented unwanted canine
movement.
PMID- 29333591
TI - Differential Inhibition of Nav1.7 and Neuropathic Pain by Hybridoma-Produced and
Recombinant Monoclonal Antibodies that Target Nav1.7 : Differential activities of
Nav1.7-targeting monoclonal antibodies.
AB - The voltage-gated Na+ channel subtype Nav1.7 is important for pain and itch in
rodents and humans. We previously showed that a Nav1.7-targeting monoclonal
antibody (SVmab) reduces Na+ currents and pain and itch responses in mice. Here,
we investigated whether recombinant SVmab (rSVmab) binds to and blocks Nav1.7
similar to SVmab. ELISA tests revealed that SVmab was capable of binding to
Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the
voltage-sensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding
to Nav1.7 in these tests. Patch-clamp recordings showed that SVmab, but not
rSVmab, markedly inhibited Na+ currents in Nav1.7-expressing HEK293 cells.
Notably, electrical field stimulation increased the blocking activity of SVmab
and rSVmab in Nav1.7-expressing HEK293 cells. SVmab was more effective than
rSVmab in inhibiting paclitaxel-induced mechanical allodynia. SVmab also bound to
human DRG neurons and inhibited their Na+ currents. Finally, potential reasons
for the differential efficacy of SVmab and rSVmab and future directions are
discussed.
PMID- 29333594
TI - RAS testing for colorectal cancer patients is reliable in European laboratories
that pass external quality assessment.
AB - Wild-type status of KRAS and the NRAS gene (exon 2, 3, and 4) in the tumor should
be determined before treatment of metastatic colorectal cancer (mCRC) patients
with EGFR-targeting agents. There is a large variation in test methods to
determine RAS status, and more sensitive detection methods were recently
introduced. Data from quality assessment programs indicate substantial error
rates. This study assessed the completeness and correctness of RAS testing in
European laboratories that successfully passed external quality assessment (EQA).
Participants were requested to send material of their most recent ten patients
with mCRC who had been tested for RAS status. Isolated DNA, a hematoxylin and
eosin stained tissue slide with a marked area for macrodissection and
accompanying patient reports were requested. Samples were reevaluated in a
reference laboratory by using a next-generation sequencing approach. In total, 31
laboratories sent in the requested material (n = 309). Despite regulations for
anti-EGFR therapy, one institute did not perform full RAS testing. Reanalysis was
possible for 274 samples with sufficient DNA available. In the hotspot codons of
KRAS and NRAS, seven discordant results were obtained in total, five of them
leading to a different prediction of anti-EGFR therapy efficacy (2%; n = 274).
Results show that oncologists can rely on the quality of laboratories with good
performance in EQA. Oncologists need to be aware that the testing laboratory
participates successfully in EQA programs. Some EQA providers list the good
performing laboratories on their website.
PMID- 29333595
TI - Implanted Closed-Loop Gastric Electrical Stimulation (CLGES) System with Sensor
Based Feedback Safely Limits Weight Regain at 24 Months.
AB - BACKGROUND: Weight regain following bariatric surgery is not uncommon. Safe,
effective weight loss treatment up to 1 year has been reported with the closed
loop gastric electrical stimulation (CLGES) system. Continuous recording of
eating and activity behavior by onboard sensors is one of the novel features of
this closed-loop electrical stimulation therapy, and may provide improved long
term weight maintenance by enhancing aftercare. METHODS: Four centers
participating in a 12-month prospective multicenter randomized study monitored
all implanted participants (n = 47) up to 24 months after laparoscopic
implantation of a CLGES system. Weight loss, safety, quality of life (QOL), and
cardiac risk factors were analyzed. RESULTS: Weight regain was limited in the 35
(74%) participants remaining enrolled at 24 months. Mean percent total body
weight loss (%TBWL) changed by only 1.5% between 12 and 24 months, reported at
14.8% (95% CI 12.3 to 17.3) and 13.3% (95% CI 10.7 to 15.8), respectively. The
only serious device-/procedure-related adverse events were two elective system
replacements due to lead failure in the first 12 months, while improvements in
QOL and cardiovascular risk factors were stable thru 24 months. CONCLUSION:
During the 24 month follow-up, CLGES was shown to limit weight regain with strong
safety outcomes, including no serious adverse events in the second year. We
hypothesize that CLGES and objective sensor-based behavior data combined to
produce behavior change. The study supports CLGES as a safe obesity treatment
with potential for long-term health benefits. TRIAL REGISTRATION:
ClinicalTrials.gov identifier: NCT01448785.
PMID- 29333596
TI - Risk of adverse events associated with front-line anti-myeloma treatment in
Medicare patients with multiple myeloma.
AB - This study aims to examine the risks of adverse events associated with anti
multiple myeloma (MM) therapies in a large population-based cohort of elderly
patients with MM. Patients diagnosed with advanced MM from 2005 through 2009 and
receiving anti-MM therapy were identified from the Surveillance, Epidemiology,
and End Results (SEER)-Medicare-linked data. We compared safety outcomes between
novel agents (proteasome inhibitor (PI) and immunomodulatory drugs (IMiD)) and
other therapies and between PI- or IMiD-based regimens and PI plus IMiD
combination regimens. Of 2587 patients with advanced MM, 2048 (79%) received
novel agents and 539 (21%) received other therapies. Patients with preexisting
anemia and thrombocytopenia were significantly more likely to receive novel
agents (85.9 vs. 82.4%, P = 0.038; 13.8 vs. 10.4%, P = 0.036), while those with
preexisting cardiovascular disease and hypertension were significantly less
likely to receive novel agents (73.4 vs. 79.8%, P = 0.003; 81.3 vs. 85.2%, P =
0.035). The hazard ratios for anemia, peripheral neuropathy, and thromboembolic
events for patients receiving novel agents compared with those receiving other
therapies were 1.19 (95% CI, 1.06-1.32), 1.57 (95% CI, 1.15-2.15), and 1.31 (95%
CI, 1.03-1.67). The hazard ratios for anemia, neutropenia, and thromboembolic
events for patients receiving PI plus IMiD combination therapies compared with
those receiving PI- or IMiD-based therapies were 1.31 (95% CI, 1.12-1.54), 1.66
(95% CI, 1.27-2.18, and 1.37 (95% CI, 1.02-1.86). Novel agents significantly
increased the risk of anemia, peripheral neuropathy, and thromboembolic events.
PI plus IMiD combination therapies were associated with significantly higher risk
for anemia, neutropenia, and thromboembolic events.
PMID- 29333597
TI - TP53 polymorphism in plasma cell myeloma.
AB - INTRODUCTION: Significant and accessible predictive factors for bortezomib
treatment in plasma cell myeloma (PCM) are still lacking. TP53 codon 72
polymorphism (P72R) results in proline (P) or arginine (R) at 72 amino acid
position, which causes synthesis of proteins with distinct functions. The aims of
our study were to: 1) analyze whether this polymorphism is associated with an
increased risk of PCM; 2) study whether the P72R polymorphism affects overall
survival (OS) among PCM patients; 3) assess the possible association of the P72R
polymorphism with sensitivity to bortezomib in cell cultures derived from PCM
patients. MATERIAL AND METHODS: Genomic DNA from newly diagnosed 59 patients
(without IgVH gene rearrangements and TP53 deletions) and 50 healthy blood donors
were analyzed by RFLP-PCR to identify TP53 polymorphism. Chromosomal aberrations
were detected by use of cIg-FISH. The lymphocyte cell cultures from a subgroup of
40 PCM patients were treated with bortezomib (1, 2 and 4 nM). RESULTS: The P
allele of the P72R polymorphism was more common than the R allele in PMC patients
compared to controls (39% vs. 24%), and the difference was significant (p =
0.02). The PP and PR genotypes (in combina-tion) were more frequent among cases
than in controls (65% vs. 42%, OR = 2.32, p = 0.04). At the cell culture level
and 2 nM bortezomib concentration the PP genotype was associated with higher
necrosis rates (10.5%) compared to the PR genotype (5.7%, p = 0.006) or the RR
genotype (6.3%, p = 0.02); however, no effect of genotypes was observed at
bortezomib concentrations of 1 and 4 nM. The shortest OS (12 months) was observed
in patients with the PP genotype compared to patients with the PR or RR genotypes
(20 months) (p = 0.04). CONCLUSIONS: The results suggest that P72R polymorphisms
may be associated with an increased PCM risk and may affect OS of PCM patients.
However, we saw no consistent results of the polymorphism effect on apoptosis and
necrosis in cell cultures derived from PCM patients. Further studies are need in
this regard.
PMID- 29333598
TI - Rainer Walter Guillery FRS, 28th August 1929-7th April 2017.
PMID- 29333599
TI - Developmental coordination disorder: the role of executive functions.
PMID- 29333600
TI - The model of children's social adjustment under the gender-roles absence in
single-parent families.
AB - This study aimed to evaluate the effects of the gender-role types and child
rearing gender-role attitude of the single-parents, as well as their children's
gender role traits and family socio-economic status, on social adjustment. We
recruited 458 pairs of single parents and their children aged 8-18 by purposive
sampling. The research tools included the Family Socio-economic Status
Questionnaire, Sex Role Scales, Parental Child-rearing Gender-role Attitude Scale
and Social Adjustment Scale. The results indicated: (a) single mothers' and their
daughters' feminine traits were both higher than their masculine traits, and
sons' masculine traits were higher than their feminine traits; the majority
gender-role type of single parents and their children was androgyny; significant
differences were found between children's gender-role types depending on
different raiser, the proportion of girls' masculine traits raised by single
fathers was significantly higher than those who were raised by single mothers;
(b) family socio-economic status and single parents' gender-role types positively
influenced parental child-rearing gender-role attitude, which in turn, influenced
the children's gender traits, and further affected children's social adjustment.
PMID- 29333602
TI - Children's Perceptions of Economic Groups in a Context of Limited Access to
Opportunities.
AB - Children (N = 267, ages 8-14 years, M = 11.61 years, middle to upper-middle
income) made predictions regarding groups of same-aged peers from high-wealth and
low-wealth backgrounds. The context involved granting access to a special
opportunity. From middle childhood to early adolescence children increasingly
expected both high- and low-wealth groups to want access to opportunities for
their own group. However, children viewed high-wealth groups as motivated in part
by selfishness and low-wealth groups as concerned in part with broader economic
inequality. Finally, the higher children's family income, the more they expected
group-serving tendencies. These findings revealed children's perceptions of
exclusive preferences between economic groups, negative stereotypes about high
wealth children, and awareness of some of the constraints faced by low-wealth
children.
PMID- 29333601
TI - Risk factors for stress urinary incontinence after native-tissue vaginal repair
of pelvic organ prolapse.
AB - OBJECTIVE: To identify risk factors for postoperative stress urinary incontinence
(POSUI) after native-tissue prolapse repair without a concomitant anti
incontinence procedure. METHODS: The present single-center retrospective study
included women with genital prolapse who underwent high uterosacral ligament
suspension without a concomitant anti-incontinence procedure during 2008-2013.
Univariate and multivariate analyses were performed to identify risk factors for
POSUI (identified through clinical interview and International Consultation on
Incontinence Modular Questionnaire-Short Form [ICIQ-SF] self-administration) at 6
months. RESULTS: In total, 87 (20.9%) of 417 women developed POSUI. Preoperative
stress urinary incontinence (SUI) and urodynamically diagnosed SUI were
significantly associated with POSUI; moreover, women with POSUI had a higher
preoperative ICIQ-SF score, a lower opening detrusor pressure, and a lower
detrusor pressure at maximum flow than did women without POSUI (P<0.05 for all
comparisons). In the multivariate analysis, preoperative SUI (odds ratio 3.11), a
detrusor pressure at maximum flow of less than 30 cm H2 O (odds ratio 2.93), and
urodynamically diagnosed SUI (odds ratio 2.26) were independent risk factors for
POSUI. CONCLUSION: Preoperative urodynamic parameters, obtained before prolapse
repair surgery, were associated with POSUI and could be useful in providing
adequate counseling to facilitate decision making on whether to add a concomitant
anti-incontinence procedure.
PMID- 29333603
TI - Could conjunctivitis in patients with atopic dermatitis treated with dupilumab be
caused by colonization with Demodex and increased interleukin-17 levels?
PMID- 29333605
TI - Report on oral health status and treatment needs of 5-15 years old children with
sensory deficits in Chennai, India.
PMID- 29333604
TI - Adiponectin inhibits inflammatory cytokines production by Beclin-1
phosphorylation and B-cell lymphoma 2 mRNA destabilization: role for autophagy
induction.
AB - BACKGROUND AND PURPOSE: Adiponectin potently suppresses inflammatory mediator
production. Autophagy is known to play a critical role in the modulation of
inflammatory responses by adiponectin. However, the underlying mechanisms are not
clearly understood. Interaction between Beclin-1 and B-cell lymphoma 2 (Bcl-2) is
a critical event in autophagy induction. We examined the effects of globular
adiponectin (gAcrp) on the Beclin-1/Bcl-2 association and its underlying
mechanisms. EXPERIMENTAL APPROACH: The effect of gAcrp on the interaction between
Beclin-1 and Bcl-2 was examined by immunoprecipitation followed by Western
blotting. To elucidate the underlying mechanisms, we determined the effects of
gAcrp on Beclin-1 phosphorylation and Bcl-2 mRNA stability, and investigated
their role in the suppression of inflammatory mediators using pharmacological
inhibitors and transient target gene knockdown. KEY RESULTS: Globular adiponectin
disrupted the association between Beclin-1 and Bcl-2 and increased Beclin-1
phosphorylation at Thr119 , critical residue for binding with Bcl-2, via a death
associated protein kinase-1 (DAPK1)-dependent mechanism. Moreover, gAcrp reduced
Bcl-2 expression via Bcl-2 mRNA destabilization, without significantly affecting
Bcl-2 promoter activity and protein degradation, which was mediated by
tristetraprolin (TTP) induction. Finally, DAPK1 and TTP were shown to play key
roles in gAcrp-induced autophagosome formation and suppression of LPS-stimulated
TNF-alpha and IL-1beta expression. CONCLUSION AND IMPLICATIONS: Beclin-1
phosphorylation and Bcl-2 mRNA destabilization mediated by DAPK1 and TTP are
crucial events leading to autophagy and the suppression of inflammatory cytokine
production by gAcrp. These results provide novel mechanisms underlying
adiponectin's modulation of inflammatory responses. DAPK and TTP are potential
therapeutic targets for the management of inflammation.
PMID- 29333606
TI - Genetic relationships among Vietnamese local pigs investigated using genome-wide
SNP markers.
AB - Vietnam is one of the most important countries for pig domestication, and a total
of 26 local breeds have been reported. In the present study, genetic
relationships among the various pig breeds were investigated using 90 samples
collected from local pigs (15 breeds) in 15 distantly separated, distinct areas
of the country and six samples from Landrace pigs in Hanoi as an out-group of a
common Western breed. All samples were genotyped using the Illumina Porcine SNP60
v2 Genotyping BeadChip. We used 15 160-15 217 SNPs that showed a high degree of
polymorphism in the Vietnamese breeds for identifying genetic relationships among
the Vietnamese breeds. Principal components analysis showed that most pigs
indigenous to Vietnam formed clusters correlated with their original geographic
locations. Some Vietnamese breeds formed a cluster that was genetically related
to the Western breed Landrace, suggesting the possibility of crossbreeding. These
findings will be useful for the conservation and management of Vietnamese local
pig breeds.
PMID- 29333607
TI - Arabidopsis MLO2 is a negative regulator of sensitivity to extracellular reactive
oxygen species.
AB - The atmospheric pollutant ozone (O3 ) is a strong oxidant that causes
extracellular reactive oxygen species (ROS) formation, has significant ecological
relevance, and is used here as a non-invasive ROS inducer to study plant
signalling. Previous genetic screens identified several mutants exhibiting
enhanced O3 sensitivity, but few with enhanced tolerance. We found that loss-of
function mutants in Arabidopsis MLO2, a gene implicated in susceptibility to
powdery mildew disease, exhibit enhanced dose-dependent tolerance to O3 and
extracellular ROS, but a normal response to intracellular ROS. This phenotype is
increased in a mlo2 mlo6 mlo12 triple mutant, reminiscent of the genetic
redundancy of MLO genes in powdery mildew resistance. Stomatal assays revealed
that enhanced O3 tolerance in mlo2 mutants is not caused by altered stomatal
conductance. We explored modulation of the mlo2-associated O3 tolerance, powdery
mildew resistance, and early senescence phenotypes by genetic epistasis analysis,
involving mutants with known effects on ROS sensitivity or antifungal defence.
Mining of publicly accessible microarray data suggests that these MLO proteins
regulate accumulation of abiotic stress response transcripts, and transcript
accumulation of MLO2 itself is O3 responsive. In summary, our data reveal MLO2 as
a novel negative regulator in plant ROS responses, which links biotic and abiotic
stress response pathways.
PMID- 29333608
TI - The synergistic effect of PDT and oxacillin on clinical isolates of
Staphylococcus aureus.
AB - BACKGROUND: Staphylococcus aureus is a major pathogen in clinical microbiology.
It is known to cause infections at various body sites and can be life
threatening. The development of resistance to many well-established antibiotic
treatments and the prevalence of methicillin-resistant S. aureus (MRAS) among
hospital patients and the general community pose challenges in treating the
pathogen. The antimicrobial effect of photodynamic therapy (PDT) has been a
subject of study for a long time and can offer new strategies for dealing with
resistant strains. OBJECTIVE: In our study, we searched for a positive
synergistic relationship between PDT and the standard antibiotics used to treat
S. aureus and MRSA infections. MATERIALS AND METHODS: The phototoxic profile of
deuteroporphyrin (DP) in both resistant and susceptible clinical strains of S.
aureus was determined by plating of treated and untreated broth cultures.
Electron microscopy imaging was done to explore possible sites of damage and free
radical accumulation in the cells during DP-PDT. Minimal inhibitory concentration
(MIC) of oxacillin, gentamicin, vancomycin, rifampin, and fusidic acid was
determined using the broth dilution method, and the checkerboard method was used
to detect and evaluate the synergistic potential of DP-PDT and antibiotic
combinations. A synergistic combination was further characterized using broth
cultures and plating. RESULTS: DP-PDT using a light dose of 15 J/cm2 showed a
bactericidal effect even with a small concentration of 17 MUM DP. Transmission
electron microscopy indicated profound damage in the cell wall and cell membrane,
and the appearance of mesosome-like structures. Free radicals tend to localize in
the cell membrane and inside the mesosome. No synergistic effect was detected by
combining PDT with gentamicin, vancomycin, rifampin, and fusidic acid treatments.
A positive synergistic effect was observed only in DP-PDT-oxacillin combined
treatment using the checkerboard method. The effect was observed in clinical
antibiotic-resistant isolates after DP-PDT using a light dose of 46 J/cm2 and
small concentrations of DP. Oxacillin MIC decreased below 2 MUg/ml in resistant
strains under such conditions. Cultures which did not undergo new cycles of DP
PDT recovered their original oxacillin resistance after a few generations.
CONCLUSIONS: PDT with porphyrins shows possible new therapeutic options in
treating drug-resistant S. aureus at body sites suitable for irradiation. The
synergistic effect of DP-PDT with oxacillin on clinical strains illustrates the
potential of PDT to augment traditional antibiotic treatment based on cell wall
inhibitors. Lasers Surg. Med. 50:535-551, 2018. (c) 2018 Wiley Periodicals, Inc.
PMID- 29333609
TI - Runs of homozygosity reveal genome-wide autozygosity in Italian sheep breeds.
AB - The availability of dense single nucleotide polymorphism (SNP) assays allows for
the determination of autozygous segments based on runs of consecutive homozygous
genotypes (ROH). The aim of the present study was to investigate the occurrence
and distribution of ROH in 21 Italian sheep breeds using medium-density SNP
genotypes in order to characterize autozygosity and identify genomic regions that
frequently appeared in ROH within individuals, namely ROH islands. After
filtering, the final number of animals and SNPs retained for analyses were 502
and 46 277 respectively. A total of 12 302 ROH were identified. The mean number
of ROH per breed ranged from 10.58 (Comisana) to 44.54 (Valle del Belice). The
average length of ROH across breeds was 4.55 Mb and ranged from 3.85 Mb
(Biellese) to 5.51 Mb (Leccese). Valle del Belice showed the highest value of
inbreeding on the basis of ROH (FROH = 0.099), whereas Comisana showed the
lowest (FROH = 0.016), and high standard deviation values revealed high
variability in autozygosity levels within each breed. Differences also existed in
the length of ROH. Analysis of the distribution of ROH according to their size
showed that, for all breeds, the majority of the detected ROH were <10 Mb in
length, with a few long ROH >25 Mb. The levels of ROH that we estimated here
reflect the inbreeding history of the investigated sheep breeds. These results
also highlight that ancient and recent inbreeding have had an impact on the
genome of the Italian sheep breeds and suggest that several animals have
experienced recent autozygosity events. Comisana and Bergamasca appeared as the
less consanguineous breeds, whereas Barbaresca, Leccese and Valle del Belice
showed ROH patterns typically produced by recent inbreeding. Moreover, within the
genomic regions most commonly associated with ROH, several candidate genes were
detected.
PMID- 29333610
TI - Clinical features and treatment of nonalcoholic fatty liver disease across the
Asia Pacific region-the GO ASIA initiative.
AB - BACKGROUND: The Gut and Obesity Asia (GO ASIA) workgroup was formed to study the
relationships between obesity and gastrointestinal diseases in the Asia Pacific
region. AIM: To study factors associated with nonalcoholic steatohepatitis (NASH)
and advanced fibrosis, and medical treatment of biopsy-proven nonalcoholic fatty
liver disease (NAFLD) patients. METHODS: Retrospective study of biopsy-proven
NAFLD patients from centres in the GO ASIA Workgroup. Independent factors
associated with NASH and with advanced fibrosis on binary logistic regression
analyses in a training cohort were used for the development of their
corresponding risk score, which were validated in a validation cohort. RESULTS:
We included 1008 patients from nine centres across eight countries (NASH 62.9%,
advanced fibrosis 17.2%). Independent predictors of NASH were body mass index
>=30 kg/m2 , diabetes mellitus, dyslipidaemia, alanine aminotransferase >=88 U/L
and aspartate aminotransferase >=38 U/L, constituting the Asia Pacific NASH risk
score. A high score has a positive predictive value of 80%-83% for NASH.
Independent predictors of advanced fibrosis were age >=55 years, diabetes
mellitus and platelet count <150 * 109 /L, constituting the Asia-Pacific NAFLD
advanced fibrosis risk score. A low score has a negative predictive value of 95%
96% for advanced fibrosis. Only 1.7% of patients were referred for structured
lifestyle program, 4.2% were on vitamin E, and 2.4% were on pioglitazone.
CONCLUSIONS: More severe liver disease can be suspected or ruled out based on
factors identified in this study. Utilisation of structured lifestyle program,
vitamin E and pioglitazone was limited despite this being a cohort of biopsy
proven NAFLD patients with majority of patients having NASH.
PMID- 29333611
TI - Cognitive dysfunction after generalized tonic-clonic status epilepticus in
adults.
AB - OBJECTIVES: Generalized tonic-clonic status epilepticus (GTC-SE) is considered a
risk for cognitive impairment. Research with standardized tools is scarce and non
conclusive. We systematically assessed short-term and long-term cognitive
function after GTC-SE. MATERIALS AND METHODS: Thirty-three patients were tested
after the clinical post-ictal phase of GTC-SE (timepoint 1) and again after 1
year (timepoint 2). Twenty controls were examined with the same tests. Tests from
Cambridge Neuropsychological Test Automated Battery were used. Motor screening
test (MOT) assessed motor speed, delayed matching to sample (DMS) and paired
associates learning (PAL) assessed memory, and Stockings of Cambridge (SOC)
assessed executive function. Estimated premorbid IQ and radiologically visible
brain lesions were controlled for in adjusted results. Outcome measures were z
scores, the number of standard deviations a score deviates from the mean of a
norm population. RESULTS: At timepoint 1, unadjusted patient results were
significantly below both norm and control group performances on all subtests.
Patient mean was 1.9 z-scores below controls (P < .001) on PAL total errors.
Results remained significant for PAL and DMS after adjustments. Patient results
improved at timepoint 2, but memory tests remained lower than norms and for
controls. An executive dysfunction emerged on the most complex SOC stage (z-score
difference -0.83; P = .008, adjusted difference -0.94; P = .02). CONCLUSIONS:
Memory and learning impairment in the early phase after SE and late developing
executive dysfunction remained significant after adjusting for estimated
premorbid IQ and pre-SE brain lesions. Results suggest that GTC-SE poses a risk
for cognitive impairment.
PMID- 29333612
TI - Fosfomycin residues in colostrum: Impact on morpho-physiology and microbiology of
suckling piglets.
AB - Fosfomycin is a broad-spectrum bactericidal antibiotic widely used in pig farms
for the treatment of a wide variety of bacterial infections. In this study, the
elimination of disodium fosfomycin in colostrum/milk of the sow and the impact of
this antibiotic on the microbiota and intestinal morpho-physiology of suckling
piglets were analyzed. The average amount of fosfomycin eliminated in colostrum
(after administration of 15 mg/kg IM) during the first 10 hr postpartum was 0.85
MUg/ml, and the mean residual amount ingested by the piglets was 0.26 mg/kg. The
elimination profile of fosfomycin concentrations in colostrum occurs at a time of
profound changes in the morpho-physiology of the gastrointestinal tract of the
piglet. However, the studied concentrations did not produce imbalances on the
microbiota or on the morpho-physiology of the gastrointestinal tract of the
piglet. Concentrations of fosfomycin were maintained in the mammary gland above
the MIC for more than 8 hr for pathogenic bacteria of productive importance. This
would indicate that fosfomycin may be considered safe for the specific treatment
of bacterial infectious processes in sows during the peri- and postpartum period.
This first study with disodium fosfomycin stimulates awareness in the proper use
of antimicrobials at farrowing.
PMID- 29333613
TI - Pharmacokinetics, pharmacodynamics and clinical use of trazodone and its active
metabolite m-chlorophenylpiperazine in the horse.
AB - Trazodone is a serotonin receptor antagonist and reuptake inhibitor used
extensively as an anxiolytic in human and small animal veterinary medicine. The
aims of this study were to determine the pharmacokinetics of oral trazodone in
experimental horses and to evaluate the effect of oral trazodone in clinical
horses. Six experimental horses were administered trazodone at 7.5 or 10 mg/kg.
Plasma concentrations of trazodone and its metabolite (m-CPP) were determined via
UPLC-MS/MS. Noncompartmental pharmacokinetic analysis, sedation and ataxia scores
were determined. Trazodone was rapidly absorbed after oral administration with a
maximum concentration of 2.5-4.1 MUg/ml and half-life of the terminal phase of
approximately 7 hr. The metabolite was present at low levels in all horses,
representing only 2.5% of the total area under the curve. In experimental horses,
concentration-dependent sedation and ataxia were noted, lasting up to 12 hr. For
clinical cases, medical records of horses treated with trazodone for various
abnormal behaviours were reviewed and data were summarized. Trazodone was
successful in modifying behavioural problems to some degree in 17 of 18 clinical
cases. Tolerance and subsequent lack of drug effect occurred in two of 18
clinical cases following 14 or 21 days of use. In both populations of horses,
adverse effects attributed to trazodone include oversedation, muscle
fasciculations and transient arrhythmias.
PMID- 29333614
TI - The effect of risk factor misclassification on the partial population
attributable risk.
AB - The partial population attributable risk (pPAR) is used to quantify the
population-level impact of preventive interventions in a multifactorial disease
setting. In this paper, we consider the effect of nondifferential risk factor
misclassification on the direction and magnitude of bias of pPAR estimands and
related quantities. We found that the bias in the uncorrected pPAR depends
nonlinearly and nonmonotonically on the sensitivities, specificities, relative
risks, and joint prevalence of the exposure of interest and background risk
factors, as well as the associations between these factors. The bias in the
uncorrected pPAR is most dependent on the sensitivity of the exposure. The
magnitude of bias varies over a large range, and in a small region of the
parameter space determining the pPAR, the direction of bias is away from the
null. In contrast, the crude PAR can only be unbiased or biased towards the null
by risk factor misclassification. The semiadjusted PAR is calculated using the
formula for the crude PAR but plugs in the multivariate-adjusted relative risk.
Because the crude and semiadjusted PARs continue to be used in public health
research, we also investigated the magnitude and direction of the bias that may
arise when using these formulae instead of the pPAR. These PAR estimators and
their uncorrected counterparts were calculated in a study of risk factors for
colorectal cancer in the Health Professionals Follow-up Study, where it was found
that because of misclassification, the pPAR for low folate intake was
overestimated with a relative bias of 48%, when red meat and alcohol intake were
treated as misclassified risk factors that are not modified, and when red meat
was treated as the modifiable risk factor, the estimated value of the pPAR went
from 14% to 60%, further illustrating the extent to which misclassification can
bias estimates of the pPAR.
PMID- 29333615
TI - Circular RNA hsa_circ_0000567 can be used as a promising diagnostic biomarker for
human colorectal cancer.
AB - BACKGROUND: Recent studies have revealed that circular RNAs are involved in the
biological process of some kinds of human cancers. However, little is known about
their diagnostic values and functions in colorectal cancer (CRC). METHODS: The
expression levels of hsa_circ_0000567 in 102 paired CRC tissues and adjacent
noncancerous tissues, 5 CRC cell lines, and a normal colorectal epithelial cell
line were detected by quantitative real-time polymerase chain reaction (qRT-PCR).
The correlations between hsa_circ_0000567 expression levels and the
clinicopathological factors of patients with CRC were analyzed. Furthermore, the
loss-of-function assay was performed to investigate the functions of
hsa_circ_0000567 in vitro. Finally, a receiver operating characteristic (ROC)
curve was established to evaluate the diagnostic value of hsa_circ_0000567.
RESULTS: Hsa_circ_0000567 expression was significantly downregulated in CRC
tissues and CRC cell lines. In addition, the decreased hsa_circ_0000567
expression in CRC was negatively correlated with tumor size (P = .011), lymph
metastasis (P = .003), distal metastasis (P < .0001), and tumor-node-metastasis
(TNM) stage (P = .003) in CRC. Moreover, knockdown of hsa_circ_0000567 promoted
CRC cells proliferation and migration in vitro. Importantly, the area under the
ROC curve (AUC) was 0.8653, which indicates hsa_circ_0000567 can serve as a
diagnostic biomarker. CONCLUSION: Hsa_circ_0000567 may be a novel suppressor and
a potential diagnosis biomarker in CRC.
PMID- 29333616
TI - Determination of vitamins K1 , MK-4, and MK-7 in human serum of postmenopausal
women by HPLC with fluorescence detection.
AB - BACKGROUND: New high-performance liquid chromatography (HPLC) method was
developed for the determination of vitamin K1 and two forms of vitamin K2 (MK-4
and MK-7) in human serum, and the levels of vitamin K were determined in 350
samples of postmenopausal women. METHODS: Vitamin K was determined by HPLC with
fluorescence detection after postcolumn zinc reduction. The detection was
performed at 246 nm (excitation) and 430 nm (emission). The internal standard and
2 mL of ethanol were added to 500 MUL of serum. The mixture was extracted with 4
mL of hexane, and solid phase extraction was then used. RESULTS: The HLPC method
was fully validated. The intra- and interday accuracy and precision were
evaluated on two QC samples by multiple analysis, and CV were less than 10%. The
limit of quantification for MK-4 was found at 0.04 ng/mL, for K1 0.03 ng/mL, and
for MK-7 0.03 ng/mL. The mean recoveries of the corresponding compounds were 98%
110%. Serum levels of MK-4, K1 , and MK-7 in postmenopausal women with
osteoporosis were 0.890 +/- 0.291 ng/mL, 0.433 +/- 0.394 ng/mL, and 1.002 +/-
1.020 ng/mL, respectively (mean +/- SD). Serum levels of MK-4, K1 , and MK-7 in
postmenopausal women without osteoporosis were 0.825 +/- 0.266 ng/mL, 0.493 +/-
0.399 ng/mL, and 1.186 +/- 1.076 ng/mL, respectively (mean +/- SD). CONCLUSION:
New HPLC method for the determination of vitamins K1 , MK-4, and MK-7 in serum
was evaluated and validated. This method is highly specific and sensitive with
the low limit of quantification.
PMID- 29333617
TI - A perceptive plus in Parkinson's disease.
PMID- 29333618
TI - Age-associated urethral dysfunction in urethane-anesthetized rats.
AB - AIMS: We aimed to investigate the age-associated changes in movement coordination
between the urinary bladder and the urethra in rats. METHODS: A total of 17
female Sprague-Dawley rats were used. The rats were divided into young (3 months
old) and middle-aged (12-15 months old) groups. In both groups, isovolumetric
cystometry and urethral perfusion pressure (UPP) measurements were performed
under urethane anesthesia. After the rhythmic bladder contractions stabilized, L
arginine, a nitric oxide (NO) substrate (100 mg/kg), was administered
intravenously in both groups. Subsequently, N-nitro-L-arginine methyl ester
hydrochloride (L-NAME) (50 mg/kg) was injected intravenously to inhibit NO
synthase activity in both groups. RESULTS: UPP change, defined as UPP nadir minus
baseline UPP, was significantly smaller in middle-aged rats (64%) than in young
rats (P < 0.05). The mean amplitude of high-frequency oscillations (HFOs) of the
external urethral sphincter was also significantly lower (62%) in middle-aged
rats than that in young rats (P < 0.05). Urethral contraction during UPP change
was also noted in middle-aged rats. This urethral contraction disappeared after L
arginine administration. UPP nadir during bladder contraction was inhibited by L
NAME in both groups. UPP change was greater in middle-aged rats than in young
rats, and 3 out of 9 middle-aged rats showed a detrusor-sphincter dyssynergia
pattern after L-NAME. CONCLUSIONS: The results indicated that aging induces
dysfunction in movement coordination between the urinary bladder and the urethra.
Thus, age-associated urethral dysfunctions may lead to inefficient voiding with
increased post-void residual urine volume, which is often observed in elderly
populations.
PMID- 29333620
TI - In-center hemodialysis education: Challenges and innovations in training of
fellows in nephrology.
AB - The in-center dialysis unit and practice of dialysis, in the current multi-team
approach, requires knowledge and skills in all the domains including medical
expert, communicator, collaborator, scholar, health advocate, and leader. We are
tasked as a community, to embrace and incentivize new innovations and technology
to address these needs for our post graduate trainees. These innovations must
address the basic principles of dialysis, quality improvement, technical and
procedural skills as well as leadership and administration skills. The teaching
methods and innovations must also be challenged to demonstrate the translation
into adoption and improvements in practice to demonstrate success. This article
will review the current state of the training curriculum in Nephrology for in
center hemodialysis and address some of the recent innovations.
PMID- 29333619
TI - Surrogate scale for evaluating respiratory function based on complete blood count
parameters.
AB - BACKGROUND: In this study, we aimed to identify a simple method for evaluating
respiratory function using complete blood count parameters. METHODS: The complete
blood count parameters, including red blood cell (RBC) count, hemoglobin (Hb)
level, lymphocyte (Lym) and platelet (Plt) count, and partial pressure of oxygen
(PO2 ) level, were measured using automated analyzers in patients with chronic
obstructive pulmonary disease (COPD), aged subjects, and young subjects (control
group). The red cell index (RCI) was calculated using the following equation:
(RBC * Hb)/(Lym * Plt); in theory, the RCI is inversely proportional to the
respiratory function. RESULTS: We observed a significant relationship between the
RCI and PCO2 values, and between the RCI and FEV1/FVC values (P < .05). The RCI
in the COPD, and aged subject groups were all significantly higher than that in
the control group (P < .05). The cutoff value for normal respiratory function was
2.3. The positive rates for an abnormal increase in RCI were also considerably
higher in each observation group than in the control group (P < .05). CONCLUSION:
The RCI can be considered as a simple and effective tool for evaluating
respiratory function.
PMID- 29333621
TI - Characterization of mouse neuro-urological dynamics in a novel decerebrate
arterially perfused mouse (DAPM) preparation.
AB - AIM: To develop the decerebrate arterially perfused mouse (DAPM) preparation, a
novel voiding model of the lower urinary tract (LUT) that enables in vitro-like
access with in vivo-like neural connectivity. METHODS: Adult male mice were
decerebrated and arterially perfused with a carbogenated, Ringer's solution to
establish the DAPM. To allow distinction between central and peripheral actions
of interventions, experiments were conducted in both the DAPM and in a "pithed"
DAPM which has no brainstem or spinal cord control. RESULTS: Functional
micturition cycles were observed in response to bladder filling. During each
void, the bladder showed strong contractions and the external urethral sphincter
(EUS) showed bursting activity. Both the frequency and amplitude of non-voiding
contractions (NVCs) in DAPM and putative micromotions (pMM) in pithed DAPM
increased with bladder filling. Vasopressin (>400 pM) caused dyssynergy of the
LUT resulting in retention in DAPM as it increased tonic EUS activity and basal
bladder pressure in a dose-dependent manner (basal pressure increase also noted
in pithed DAPM). Both neuromuscular blockade (vecuronium) and autonomic ganglion
blockade (hexamethonium), initially caused incomplete voiding, and both drugs
eventually stopped voiding in DAPM. Intravesical acetic acid (0.2%) decreased the
micturition interval. Recordings from the pelvic nerve in the pithed DAPM showed
bladder distention-induced activity in the non-noxious range which was associated
with pMM. CONCLUSIONS: This study demonstrates the utility of the DAPM which
allows a detailed characterization of LUT function in mice.
PMID- 29333622
TI - Metabolic acidosis and anaemia associated with dorzolamide in a patient with
impaired renal function.
AB - Topical carbonic anhydrase inhibitors (CAI), used for treatment of glaucoma, are
generally regarded as safe and unconnected with systemic side effects. We report
an unusual case of fatigue, metabolic acidosis, and normocytic anaemia associated
with ocular administration of the CAI, dorzolamide, in a patient with impaired
renal function. In chronic kidney disease, where CAI elimination may be
decreased, and patients prone to develop metabolic acidosis, systemic absorption
of ocular administered CAI could lead to rare, but potentially serious adverse
reaction, that are a consequence of inhibition of extraocular carbonic anhydrase
isoenzymes.
PMID- 29333624
TI - Turning fifty: join the FEBS Letters anniversary celebrations!: The FEBS Letters
Editorial Team.
PMID- 29333623
TI - Evaluation of universal immunohistochemical screening of sebaceous neoplasms in a
service setting.
AB - BACKGROUND: Muir-Torre syndrome (MTS) is a subtype of Lynch syndrome, which
encompasses the combination of sebaceous skin tumours or keratoacanthomas and
internal malignancy, due to mutations in DNA mismatch repair genes. Sebaceous
neoplasms (SNs) may occur before other malignancies, and may lead to the
diagnosis, which allows testing of other family members, cancer surveillance,
risk-reducing surgery or prevention therapies. AIM: To evaluate the efficacy of
universal immunohistochemistry (IHC) screening of SNs in a service setting.
METHODS: Patients with SNs were ascertained by a regional clinical pathology
service over a 3-year period. Results of tumour IHC, clinical genetics notes and
germline genetic testing were retrospectively reviewed. RESULTS: In total, 62
patients presented with 71 SNs; 9 (15%) of these patients had previously
diagnosed MTS. Tumour IHC was performed for 50 of the 53 remaining patients
(94%); 26 (52%) had loss of staining of one or more mismatch repair proteins.
Fifteen patients were referred to the Clinical Genetics department, and 10
patients underwent germline genetic testing. Two had a new diagnosis of MTS
confirmed, with heterozygous pathogenic mutations detected in the MSH2 and PMS2
genes (diagnostic yield 20%). The PMS2 mutation was identified in a 57-year-old
woman with a sebaceous adenoma and history of endometrial cancer; to our
knowledge, this is the first time a PMS2 mutation has been reported in MTS.
CONCLUSIONS: Universal IHC screening of SNs is an effective method to identify
cases for further genetic evaluation. Rates of referral to clinical genetics were
only moderate (58%). Increased awareness of MTS could help improve the rate of
onward referral.
PMID- 29333625
TI - K3 Li3 Gd7 (BO3 )9 : A New Gadolinium-Rich Orthoborate for Cryogenic Magnetic
Cooling.
AB - Magnetic cooling technology based on magnetocaloric effect (MCE) has attracted
great interest in obtaining extremely low temperatures, for example, for space
exploration. Here, we grew a new gadolinium-rich orthoborate K3 Li3 Gd7 (BO3 )9
(1) as a promising cryogenic magnetic coolant. It exhibits a complicated three
dimensional framework constructed from BO3 groups and gadolinium-oxygen chains.
The Gd-O chain consists of two types of clusters of Gd3 O20 and Gd3 O19
interconnection by Gd(4)O8 polyhydron. Due to its high gadolinium concentration,
a large -DeltaSm of 56.6 J kg-1 K-1 for 1 was obtained at 2 K and DeltaH=7 T,
much larger than that of the commercial benchmark Gd3 Ga5 O12 (GGG) crystal (38.4
J kg-1 K-1 ), suggesting it to be an excellent MCE material.
PMID- 29333626
TI - Effect of astaxanthin on the quality of boar sperm stored at 17 degrees C,
incubated at 37 degrees C or under in vitro conditions.
AB - The aim of the study was to investigate the effect of the antioxidant astaxanthin
on boar semen. Twenty ejaculates from 10 boars (two ejaculates/boar) were
extended and split in three groups: semen control (SC), solvent control (C; semen
with dimethyl sulfoxide, the diluent of astaxanthin) and semen with astaxanthin
(A) in concentration 0.5 MUmol/L. Sperm quality parameters (motility and
kinetics, morphology, viability, functional integrity of sperm plasma membrane by
Hypo-Osmotic Swelling Test [HOST] and DNA integrity) were assessed at 0, 24 and
48 hr of storage at 17 degrees C (experiment I), before (0 hr) and after (1 hr)
of sperm thermal resistance assay at 37 degrees C (experiment II) and finally
before (0 hr) and after (1 hr) sperm in vitro incubation (38.5 degrees C, 5% CO2
, maximum humidity [experiment III]). In experiment I, group A performed overall
better than group SC and as a tendency better than group C regarding viability.
Total motility, rapid spermatozoa and HOST remained constant across time in group
A, whereas they decreased in the remaining groups. In experiment II, regarding
motility and viability, group A displayed better results across time than the
other two groups. In experiment III, viability and total motility decreased in
groups SC and C, while in group A, these parameters were not significantly
different between the examination time points. In conclusion, astaxanthin has a
beneficial and protective effect on boar semen quality under the investigated
conditions.
PMID- 29333627
TI - Saturable Absorption in 2D Ti3 C2 MXene Thin Films for Passive Photonic Diodes.
AB - MXenes comprise a new class of 2D transition metal carbides, nitrides, and
carbonitrides that exhibit unique light-matter interactions. Recently, 2D Ti3
CNTx (Tx represents functional groups such as ?OH and ?F) was found to exhibit
nonlinear saturable absorption (SA) or increased transmittance at higher light
fluences, which is useful for mode locking in fiber-based femtosecond lasers.
However, the fundamental origin and thickness dependence of SA behavior in MXenes
remain to be understood. 2D Ti3 C2 Tx thin films of different thicknesses are
fabricated using an interfacial film formation technique to systematically study
their nonlinear optical properties. Using the open aperture Z-scan method, it is
found that the SA behavior in Ti3 C2 Tx MXene arises from plasmon-induced
increase in the ground state absorption at photon energies above the threshold
for free carrier oscillations. The saturation fluence and modulation depth of Ti3
C2 Tx MXene is observed to be dependent on the film thickness. Unlike other 2D
materials, Ti3 C2 Tx is found to show higher threshold for light-induced damage
with up to 50% increase in nonlinear transmittance. Lastly, building on the SA
behavior of Ti3 C2 Tx MXenes, a Ti3 C2 Tx MXene-based photonic diode that breaks
time-reversal symmetry to achieve nonreciprocal transmission of nanosecond laser
pulses is demonstrated.
PMID- 29333628
TI - Re(bpy)(CO)3 Cl Immobilized on Bipyridine-Periodic Mesoporous Organosilica for
Photocatalytic CO2 Reduction.
AB - This paper describes the physicochemical properties of a rhenium (Re) complex
[Re(bpy)(CO)3 Cl] immobilized on a bipyridine-periodic mesoporous organosilica
(BPy-PMO) acting as a solid support. The immobilized Re complex generated a metal
to-ligand charge transfer absorption band at 400 nm. This wavelength is longer
than that exhibited by Re(bpy)(CO)3 Cl in the polar solvent acetonitrile (371 nm)
and is almost equal to that in nonpolar toluene (403 nm). The photocatalytic
activity of this heterogeneous Re complex was lower than that of a homogeneous Re
complex due to the reduced phosphorescence lifetime resulting from
immobilization. However, the catalytic activity was enhanced by the co
immobilization of the ruthenium (Ru) photosensitizer [Ru(bpy)3 ]2+ on the PMO
pore surfaces. Quantum chemical calculations suggest that electron transfer
between the Ru and Re complexes occurs through interactions between the molecular
orbitals in the pore walls. These results should have applications to the design
of efficient heterogeneous CO2 reduction photocatalysis systems.
PMID- 29333629
TI - Surface Engineering for Extremely Enhanced Charge Separation and Photocatalytic
Hydrogen Evolution on g-C3 N4.
AB - Reinforcing the carrier separation is the key issue to maximize the
photocatalytic hydrogen evolution (PHE) efficiency of graphitic carbon nitride (g
C3 N4 ). By a surface engineering of gradual doping of graphited carbon rings
within g-C3 N4 , suitable energy band structures and built-in electric fields are
established. Photoinduced electrons and holes are impelled into diverse
directions, leading to a 21-fold improvement in the PHE rate.
PMID- 29333630
TI - Efficient Supercapacitor Energy Storage Using Conjugated Microporous Polymer
Networks Synthesized from Buchwald-Hartwig Coupling.
AB - Supercapacitors have received increasing interest as energy storage devices due
to their rapid charge-discharge rates, high power densities, and high durability.
In this work, novel conjugated microporous polymer (CMP) networks are presented
for supercapacitor energy storage, namely 3D polyaminoanthraquinone (PAQ)
networks synthesized via Buchwald-Hartwig coupling between 2,6
diaminoanthraquinone and aryl bromides. PAQs exhibit surface areas up to 600 m2 g
1 , good dispersibility in polar solvents, and can be processed to flexible
electrodes. The PAQs exhibit a three-electrode specific capacitance of 576 F g-1
in 0.5 m H2 SO4 at a current of 1 A g-1 retaining 80-85% capacitances and nearly
100% Coulombic efficiencies (95-98%) upon 6000 cycles at a current density of 2 A
g-1 . Asymmetric two-electrode supercapacitors assembled by PAQs show a
capacitance of 168 F g-1 of total electrode materials, an energy density of 60 Wh
kg-1 at a power density of 1300 W kg-1 , and a wide working potential window (0
1.6 V). The asymmetric supercapacitors show Coulombic efficiencies up to 97% and
can retain 95.5% of initial capacitance undergo 2000 cycles. This work thus
presents novel promising CMP networks for charge energy storage.
PMID- 29333631
TI - Is ejection fraction in heart failure a limitation or an opportunity?
PMID- 29333632
TI - Binding of Cu+ and Cu2+ with peptides: Peptides = oxytocin, Arg8 -vasopressin,
bradykinin, angiotensin-I, substance-P, somatostatin, and neurotensin.
AB - The intrinsic binding ability of 7 natural peptides (oxytocin, arg8 -vasopressin,
bradykinin, angiotensin-I, substance-P, somatostatin, and neurotensin) with
copper in 2 different oxidation states (CuI/II ) derived from different Cu+/2+
precursor sources have been investigated for their charge-dependent binding
characteristics. The peptide-CuI/II complexes, [M - (n-1)H + nCuI ] and [M - (2n
1)H + nCuII ], are prepared/generated by the reaction of peptides with CuI
solution/Cu-target and CuSO4 solution and are analyzed by using matrix-assisted
laser desorption/ionization (MALDI) time-of-flight mass spectrometry. The MALDI
mass spectra of both [M - (n-1)H + nCuI ] and [M - (2n-1)H + nCuII ] complexes
show no mass shift due to the loss of ?H atoms in the main chain ?NH of these
peptides by Cu+ and Cu2+ deprotonation. The measured m/z value indicates the
reduction of CuI/II oxidation state into Cu0 during MALDI processes. The number
and relative abundance of Cu+ bound to the peptides are greater compared with the
Cu2+ bound peptides. Oxytocin, arg8 -vasopressin, bradykinin, substance-P, and
somatostatin show the binding of 5Cu+ , and angiotensin-I and neurotensin show
the binding of 7Cu+ from both CuI and Cu targets, while bradykinin shows the
binding of 2Cu2+ , oxytocin, arg8 -vasopressin, angiotensin-I, and substance-P;
somatostatin shows the binding of 3Cu2+ ; and neurotensin shows 4Cu2+ binding.
The binding of more Cu+ with these small peptides signifies that the bonding
characteristics of both Cu+ and Cu2+ are different. The amino acid residues
responsible for the binding of both Cu+ and Cu2+ in these peptides have been
identified based on the density functional theory computed binding energy values
of Cu+ and the fragment transformation method predicted binding preference of
Cu2+ for individual amino acids.
PMID- 29333633
TI - Long-term outcome of stereotactic body radiotherapy for patients with small
hepatocellular carcinoma.
AB - AIM: To evaluate the long-term outcome of stereotactic body radiotherapy in
patients with small hepatocellular carcinoma who were ineligible for resection or
ablation therapies. METHODS: A total of 65 patients with 74 hepatocellular
carcinomas (median tumor size 16 mm) were enrolled in the present study. They
were treated with the prescribed dose of 48 Gy in four fractions at the
isocenter. We extended the observation period and analyzed long-term outcomes,
including overall survival, progression-free survival, local control, and various
prognostic factors, in these patients. RESULTS: The median follow-up period was
41 months for all patients and 62 months for surviving patients. The 3- and 5
year overall survival rates were 56.3% (95% confidence interval, 44.1-68.5%) and
41.4% (95% confidence interval, 28.7-54.1%), respectively. The 3- and 5-year
progression-free survival rates were 25.4% (95% confidence interval, 14.0-36.8%)
and 10.6% (95% confidence interval, 1.5-19.8%), respectively. The 3- and 5-year
local control rates were both 100% (95% confidence interval 100%). Liver
toxicities exceeding grade 3 were observed in 15 patients (23.1%). The proportion
of patients who had grade >=3 toxicities did not increase. Adverse effects (grade
<=2) presented as significant prognostic factors of overall survival, while TNM
stage (T1N0M0) was a significant prognostic factor of progression-free survival
after multivariate analysis. CONCLUSIONS: Stereotactic body radiotherapy was
effective for patients with small hepatocellular carcinomas who were ineligible
for resection or ablation therapies. The incidence of grade >=3 adverse effects
did not increase, even after longer follow-up times.
PMID- 29333634
TI - Euthanasia and the nature of suffering in addiction.
PMID- 29333635
TI - The changing relationship between bronchopulmonary dysplasia and cognition in
very preterm infants.
AB - AIM: To characterise the relationship between bronchopulmonary dysplasia (BPD)
severity and cognition in the post-surfactant era. METHODS: This was a single
centre retrospective analysis of a cohort of infants born 2009-2012. Inclusion
criteria were as follows: admission within 48 hours of birth, gestational age 22
0/7-31-6/7 weeks, birthweight 400-1500 g and Bayley Scales of Infant and Toddler
Development-III testing at 18-26 months corrected age. Infants (n = 151) were
classified by BPD severity with the NIH Workshop definition. Generalised linear
modelling and multivariate logistic regression were performed. RESULTS: Bayley
cognitive score was not associated with BPD severity in univariate (p = 0.053) or
multivariate (p = 0.503) analysis. About 27% of infants with no/mild BPD, 33% of
infants with moderate BPD and 40% of infants with severe BPD had a cognitive
score <85. There was no difference in the odds of cognitive score <85 based on
BPD severity in univariate (p = 0.485) or multivariate analysis (p = 0.225). All
infants with cognitive score <70 had severe BPD, although the association between
cognitive score <70 and BPD severity was not significant. CONCLUSION: We found no
independent effect of BPD severity level on cognition. The likelihood of a
cognitive score <85 was not associated with BPD severity.
PMID- 29333636
TI - In search of markers of pulmonary vascular remodelling in pulmonary hypertension
due to left heart disease.
PMID- 29333638
TI - Rapid profiling of polymeric phenolic acids in Salvia miltiorrhiza by hybrid data
dependent/targeted multistage mass spectrometry acquisition based on expected
compounds prediction and fragment ion searching.
AB - Phenolic acids are the major water-soluble components in Salvia miltiorrhiza
(>5%). According to previous studies, many of them contribute to the
cardiovascular effects and antioxidant effects of S. miltiorrhiza. Polymeric
phenolic acids can be considered as the tanshinol derived metabolites, e.g.,
dimmers, trimers, and tetramers. A strategy combined with tanshinol-based
expected compounds prediction, total ion chromatogram filtering, fragment ion
searching, and parent list-based multistage mass spectrometry acquisition by
linear trap quadropole-orbitrap Velos mass spectrometry was proposed to rapid
profile polymeric phenolic acids in S. miltiorrhiza. More than 480 potential
polymeric phenolic acids could be screened out by this strategy. Based on the
fragment information obtained by parent list-activated data dependent multistage
mass spectrometry acquisition, 190 polymeric phenolic acids were characterized by
comparing their mass information with literature data, and 18 of them were
firstly detected from S. miltiorrhiza. Seven potential compounds were tentatively
characterized as new polymeric phenolic acids from S. miltiorrhiza. This strategy
facilitates identification of polymeric phenolic acids in complex matrix with
both selectivity and sensitivity, which could be expanded for rapid discovery and
identification of compounds from complex matrix.
PMID- 29333637
TI - Increased free Zn2+ correlates induction of sarco(endo)plasmic reticulum stress
via altered expression levels of Zn2+ -transporters in heart failure.
AB - Zn2+ -homoeostasis including free Zn2+ ([Zn2+ ]i ) is regulated through Zn2+
transporters and their comprehensive understanding may be important due to their
contributions to cardiac dysfunction. Herein, we aimed to examine a possible role
of Zn2+ -transporters in the development of heart failure (HF) via induction of
ER stress. We first showed localizations of ZIP8, ZIP14 and ZnT8 to both
sarcolemma and S(E)R in ventricular cardiomyocytes (H9c2 cells) using confocal
together with calculated Pearson's coefficients. The expressions of ZIP14 and
ZnT8 were significantly increased with decreased ZIP8 level in HF. Moreover,
[Zn2+ ]i was significantly high in doxorubicin-treated H9c2 cells compared to
their controls. We found elevated levels of ER stress markers, GRP78 and
CHOP/Gadd153, confirming the existence of ER stress. Furthermore, we measured
markedly increased total PKC and PKCalpha expression and PKCalpha-phosphorylation
in HF. A PKC inhibition induced significant decrease in expressions of these ER
stress markers compared to controls. Interestingly, direct increase in [Zn2+ ]i
using zinc-ionophore induced significant increase in these markers. On the other
hand, when we induced ER stress directly with tunicamycin, we could not observe
any effect on expression levels of these Zn2+ transporters. Additionally,
increased [Zn2+ ]i could induce marked activation of PKCalpha. Moreover, we
observed marked decrease in [Zn2+ ]i under PKC inhibition in H9c2 cells. Overall,
our present data suggest possible role of Zn2+ transporters on an intersection
pathway with increased [Zn2+ ]i and PKCalpha activation and induction of HF, most
probably via development of ER stress. Therefore, our present data provide novel
information how a well-controlled [Zn2+ ]i via Zn2+ transporters and PKCalpha can
be important therapeutic approach in prevention/treatment of HF.
PMID- 29333639
TI - Decreasing deceased donor transplant rates among children (<=6 years) under the
new kidney allocation system.
AB - The Kidney Allocation System (KAS) was implemented in December 2014 with unknown
impact on the pediatric waitlist. To understand the effect of KAS on pediatric
registrants, deceased donor kidney transplant (DDKT) rate was assessed using
interrupted time series analysis and time-to-event analysis. Two allocation eras
were defined with an intermediary washout period: Era 1 (01/01/2013-09/01/2014),
Era 2 (09/01/2014-03/01/2015), and Era 3(03/01/2015-03/01/2017). When using Cox
proportional hazards, there was no significant association between allocation era
and DDKT likelihood as compared to Era 1 (Era 3: aHR: 1.07, 95% CI: 0.97-1.18, P
= .17). However, this was not consistent across all subgroups. Specifically,
while highly sensitized pediatric registrants were consistently less likely to be
transplanted than their less sensitized counterparts, this disparity was
attenuated in Era 3 (Era 1 aHR: 0.04, 95%CI: 0.01-0.14, P < .001; Era 3 aHR:
0.33, 95% CI: 0.21-0.53, P < .001) whereas the youngest registrants aged 0-6
experienced a 21% decrease in DDKT likelihood in Era 3 as compared to Era 1 (aHR:
0.79, 95% CI: 0.64-0.98, P = .03). Thus, while overall DDKT likelihood remained
stable with the introduction of KAS, registrants <= 6 years of age were
disadvantaged, warranting further study to ensure equitable access to
transplantation.
PMID- 29333640
TI - Comparing Mental Health of US Children of Immigrants and Non-Immigrants in 4
Racial/Ethnic Groups.
AB - BACKGROUND: To compare the mental health status of children of immigrant (COI)
and non-immigrant (NI) parents and to determine whether differences in mental
health status between COI and NI vary across 4 racial/ethnic groups. METHODS: We
conducted universal mental health screening of 2374 sixth graders in an urban
public school district. To screen, we administered well-validated adolescent
depression and disruptive behavior problem questionnaires. We evaluated
associations between child mental health, parent immigration status, and
race/ethnicity using binomial regression. RESULTS: Among Asian American/Pacific
Islanders and Latinos, COI had significantly higher depression and disruptive
behavior scores compared to NI. For Blacks/African Americans, children of NI
parents had significantly higher disruptive behavior scores compared to COI. For
European Americans, scores of COI and NI did not differ and were relatively low.
CONCLUSION: Our study suggests that how the emotional health of COI is faring
relative to children of NI depends on the child's race/ethnicity.
PMID- 29333641
TI - Who Eats School Breakfast? Parent Perceptions of School Breakfast in a State With
Very Low Participation.
AB - BACKGROUND: Having breakfast is correlated with health and academic benefits;
yet, many children do not consume breakfast, and participation in the federal
School Breakfast Program remains low. The purpose of this study was to examine
parent perceptions of school breakfast and identify relationships between those
who consume breakfast at school and those who do not. METHODS: A random sample of
100 schools, representing 29 school districts, across the state of Utah was
selected to participate in the survey. Administrators were asked to distribute an
online survey link to the parents of their school. Parents answered questions
about their oldest kindergarten through 12th grade child. Qualitative and
quantitative analyses were performed. RESULTS: A total of 488 parents completed
the survey. In a multilevel model, child grade level, participation in free and
reduced-price lunch, and perceive benefits to school breakfast were significantly
related to eating breakfast at school. Some major themes from the qualitative
analysis included no need for school breakfast, perception of regional values,
and logistical issues. CONCLUSIONS: Parent perception of school meals is related
to participation. This study identifies several areas of perception that could be
address through parent education to increase school breakfast participation.
PMID- 29333642
TI - Early Adolescents' Emotional Well-Being in the Classroom: The Role of Personal
and Contextual Assets.
AB - BACKGROUND: The objective was to predict early adolescents' emotional well-being
from personal and contextual assets in the classroom. Emotional well-being is a
key indicator of health. Aligned with the positive youth development (PYD)
framework, a supportive classroom environment and positive relationships with
teachers and peers were contextual assets in the present study; positive self
concept was a personal asset. METHODS: The sample was 406 grade 4 to 7 public
elementary school students from diverse backgrounds (mean = 11.27 years; SD =
0.89; 50% female). Data were self-, teacher-, and peer-reported. Structural
equation modeling (SEM) analyses were used to evaluate model fit and identify
significant pathways. RESULTS: SEM indicated a good model fit. Overall, 68% of
variability in early adolescents' emotional well-being was explained. Positive
self-concept directly predicted emotional well-being. Supportive classroom
environment predicted emotional well-being directly and indirectly through
increases in positive social relationships and self-concept. Positive social
relationships predicted well-being only indirectly through positive self-concept.
CONCLUSIONS: Contextual and personal assets are central for early adolescents'
emotional well-being. The interrelation among assets needs to be considered when
understanding, and ultimately promoting students' emotional well-being. The
present findings extend previous research and inform school-based intervention
and prevention programming and teacher professional development.
PMID- 29333643
TI - Race, Sex, and Discrimination in School Settings: A Multilevel Analysis of
Associations With Delinquency.
AB - BACKGROUND: Adolescence is a critical phase of development and experimentation
with delinquent behaviors. There is a growing body of literature exploring
individual and structural impacts of discrimination on health outcomes and
delinquent behaviors. However, there is limited research assessing how school
diversity and discrimination impact students' delinquent behaviors. In response,
the purpose of this study was to assess if individual- and school-level
indicators of discrimination and diversity were associated with student
delinquent behaviors among African American and White students. METHODS: We
analyzed Wave I (1994-1995) data from the National Longitudinal Study of
Adolescent Health. Our analysis was limited to 8947 African American and White
students (73% White, 48% male, and 88% parent >= high school education). We used
multilevel zero-inflated negative binomial regression to test the association of
individual- and school characteristics and discrimination with the number of self
reported delinquent behaviors. RESULTS: Race, sex, perceived peer inclusion, and
teacher discrimination were predictors of students' delinquent behaviors. The
average school perceived peer inclusion and percentage of African Americans in
teaching roles were associated with delinquent behaviors. CONCLUSIONS: Findings
from this study highlight the potential for intervention at the interpersonal and
school levels to reduce delinquency among African American and White students.
PMID- 29333644
TI - School Lunch Consumption Among 3 Food Service Providers in New Orleans.
AB - BACKGROUND: Louisiana has one of the highest rates of overweight and obese
children in the United States. The Healthy School Food Collaborative (HSFC) was
created to allow New Orleans's schools to select their own healthy school Food
Service Provider (FSP) with requirements for higher nutritional standards than
traditional options. The goal of this cross-sectional study was to examine
whether HSFC membership was associated with lunch consumption rates in elementary
school children. METHODS: An 8-week plate waste study examining 18,070 trays of
food among fourth and fifth graders was conducted. Participants included 7
schools and the 3 FSPs (2 HSFC and 1 non-HSFC member) that serviced them. Mixed
models analysis examined whether consumption rates of food items differed among
FSPs. RESULTS: On average, students consumed 307 cal during lunch. Analyses
showed significant differences in consumption rates of entree, vegetables, fruit,
and milk between the 3 FSPs (p < .01). The highest consumption rate was among
entrees at 65%. One HSFC provider had consumption levels consistent with the non
HSFC FSP. CONCLUSIONS: Overall, students consumed less than 60% of the US
Department of Agriculture recommended calories for school lunch. While overall
caloric consumption was higher among the non-HSFC schools, interventions to
increase lunch consumption across all schools are needed.
PMID- 29333645
TI - How Healthy Is Homeschool? An Analysis of Body Composition and Cardiovascular
Disease Risk.
AB - BACKGROUND: Public school children regularly participate in school-based physical
activity, physical education, and fitness testing. However, almost 2 million
American children are homeschooled. The purpose of this research was to assess
the body composition of elementary school-aged homeschool children and their
corresponding cardiovascular disease (CVD) risk. METHODS: This research explored
the body composition and CVD risk of 145 homeschool children aged 5-11 years
using body mass index (BMI), percent body fat, and waist circumference. Chi
square and Mann-Whitney U tests examined differences in CVD risk within the
homeschool population. RESULTS: Overall, homeschool children had average BMI z
scores (SD [range]) with a mean of -0.11 (0.97 [-3.47 to 2.53]). Unhealthy
classifications were seen in 11.2% of the sample by BMI, 19.6% by percent body
fat, and 49.7% by waist circumference. Statistical analysis revealed no
difference in CVD risk between sexes (chi2 (1) = 0.062, p = .804) or ethnicities
(chi2 (1) = 0.927, p = .336) but increased prevalence in children aged 5-9 years
(U = 1427, z = -4.559, p < .001). CONCLUSIONS: Almost half of elementary school
aged homeschool children showed increased risk for CVD and need regular
assessment of central adiposity.
PMID- 29333646
TI - Examining Predictors of Breakfast Skipping and Breakfast Program Use Among
Secondary School Students in the COMPASS Study.
AB - BACKGROUND: Many Canadian schools offer breakfast programs; however, students'
engagement in these programs is low, while breakfast skipping is highly prevalent
among youth. This study examined whether the availability of breakfast programs
supports adolescents' regular breakfast eating, and identified characteristics of
breakfast skippers who are not using these programs. METHODS: Data from 30,771
secondary school students from Ontario and Alberta, Canada, participating in Year
3 (2014-2015) of the COMPASS study were used for descriptive and logistic
regression analyses. Participants were categorized by self-reported breakfast
eating and school breakfast program use. RESULTS: Sixteen percent of participants
reported using school breakfast programs. Breakfast skipping was highly prevalent
among participants, regardless of their breakfast program use. Characteristics
significantly associated with program use included traveling to school via public
transit or a school bus, being a bullying victim, and having a high school
connectedness score. A desire to lose weight and non-involvement in school sports
were significantly associated with being a "breakfast skipper/nonprogram user."
CONCLUSIONS: School breakfast programs do not consistently support regular
breakfast eating, even among adolescents actively engaged in these programs.
Future research should identify and evaluate practices to bolster participation
in breakfast programs and promote regular breakfast eating among adolescents.
PMID- 29333647
TI - Effect of Sleep Duration, Diet, and Physical Activity on Obesity and Overweight
Elementary School Students in Shanghai.
AB - BACKGROUND: This was a cross-sectional survey to investigate the relationship of
age, parent education, sleep duration, physical activity, and dietary habits with
overweight or obesity in school-age children in Shanghai. METHODS: The survey
gathered information from 13,001 children in grades 1 through 5 (age 6 to 10
years) among 26 elementary schools in 7 districts. Activity level was evaluated
using the International Children's Leisure Activities Study Survey Questionnaire
(CLASS-C). The definitions of normal, overweight, and obese were adjusted for
each age. RESULTS: Logistic regression analysis indicated that age, being male,
having <=10 hours of sleep on non-school days, eating >=1 vegetable/day, or
drinking >=1 sugar-sweetened drink/day increased the risk for a child being
overweight or obese compared with having >10 hours of sleep or <=3 vegetables or
<=3 sugar-sweetened drinks/month (p <= .008). Having >2 hours of outdoor
activities on non-school days reduced the risk of being overweight or obese
compared with <=2 hours of outdoor activities on non-school days (p < .001).
CONCLUSIONS: We found that age, sex, sleep, and some dietary habits impacted
weight, and suggests that specific cultural and economic factors may impact risk
of a child being overweight or obese.
PMID- 29333648
TI - Physical and Social Contexts of Physical Activity Behaviors of Fifth and Seventh
Grade Youth.
AB - BACKGROUND: The purpose of this study was to characterize the temporal, social,
and physical contexts for physical activities commonly reported in a diverse
cohort of 753 boys and girls from fifth to seventh grade. METHODS: Data were
obtained from a multilevel longitudinal study, the Transitions and Activity
Changes in Kids. The Physical Activity Choices instrument assessed previous 5-day
participation in specific physical activities and their temporal, social, and
physical contexts. Mixed model repeated measure analyses of variance and
multinomial analyses examined sex differences and change over time. RESULTS:
Fifth grade boys and girls reported participation in similar activities at
similar frequencies, which declined significantly by seventh grade. One temporal
pattern, playing with younger children, changed over time from "both
inside/outside" to "outside" school. Boys and females reported more activities
performed in class/team groups over time. Most activities took place primarily at
home for all participants in both grades. CONCLUSIONS: Boys and girls reported
declines in the variety and frequency of activities from fifth to seventh grade.
There were sex-specific patterns in physical activities and groups; however, all
participants reported home as the primary location and a shift to class/team
groups over time. Schools are well-positioned to provide additional physical
activity opportunities.
PMID- 29333649
TI - Detection of gene-environment interactions in a family-based population using
SCAD.
PMID- 29333650
TI - Comments on "Longitudinal beta-binomial modeling using GEE for overdispersed
binomial data".
PMID- 29333651
TI - Corrigendum.
PMID- 29333652
TI - Establishment and characterization of a brain-cell line from kelp grouper
Epinephelus moara.
AB - A new brain-cell line, EMB, was developed from kelp grouper Epinephelus moara, a
cultured marine fish. The EMB cells were subcultured for more than 60 passages.
The cells were cultured in Leibovitz's L-15 medium (L15) supplemented with
antibiotics, foetal bovine serum (FBS), 2-mercaptoethanol (2-ME) and basic
fibroblast growth factor (bFGF). The cells could grow at 18-30 degrees C, with
the maximum growth between 24 and 30 degrees C. The optimum FBS concentration
for the cells growth ranged between 15 and 20%. Chromosome analysis indicated
that the modal chromosome number was 48 in the cells at passage 45. After being
transfected with pEGFP-N3 plasmid, the cells could successfully express green
fluorescence protein (GFP), implying that this cell line can be used for
transgenic studies. A significant cytopathic effect (CPE) was observed in the
cells after infection with Singapore grouper iridovirus (SGIV) or red spotted
grouper nervous necrosis virus (RGNNV) and the viral replication was confirmed by
quantitative real-time PCR (qrt-PCR) assay, which suggested EMB's application
potential for studies of SGIV and RGNNV.
PMID- 29333654
TI - Corrigendum.
PMID- 29333653
TI - Vitiligo-like lesions and immune checkpoint inhibition therapy: is it truly an
adverse event exclusive to patients with melanoma?
PMID- 29333655
TI - Preparation of High-Percentage 1T-Phase Transition Metal Dichalcogenide Nanodots
for Electrochemical Hydrogen Evolution.
AB - Nanostructured transition metal dichalcogenides (TMDs) are proven to be efficient
and robust earth-abundant electrocatalysts to potentially replace precious
platinum-based catalysts for the hydrogen evolution reaction (HER). However, the
catalytic efficiency of reported TMD catalysts is still limited by their low
density active sites, low conductivity, and/or uncleaned surface. Herein, a
general and facile method is reported for high-yield, large-scale production of
water-dispersed, ultrasmall-sized, high-percentage 1T-phase, single-layer TMD
nanodots with high-density active edge sites and clean surface, including MoS2 ,
WS2 , MoSe2 , Mo0.5 W0.5 S2 , and MoSSe, which exhibit much enhanced
electrochemical HER performances as compared to their corresponding nanosheets.
Impressively, the obtained MoSSe nanodots achieve a low overpotential of -140 mV
at current density of 10 mA cm-2 , a Tafel slope of 40 mV dec-1 , and excellent
long-term durability. The experimental and theoretical results suggest that the
excellent catalytic activity of MoSSe nanodots is attributed to the high-density
active edge sites, high-percentage metallic 1T phase, alloying effect and basal
plane Se-vacancy. This work provides a universal and effective way toward the
synthesis of TMD nanostructures with abundant active sites for electrocatalysis,
which can also be used for other applications such as batteries, sensors, and
bioimaging.
PMID- 29333656
TI - First case of Stevens-Johnson syndrome after rabies vaccination.
AB - We describe the first case of Stevens-Johnson syndrome (SJS) occurring 8 days
after the first dose of a three-dose rabies vaccination series. She had no
history of vaccine-related rash or other adverse drug reactions, nor had she
received any other drug therapy. The temporal relationship between the
development of SJS and the vaccination suggests that the rabies vaccination
probably was the causal agent. This case serves as a warning of a distinct
cutaneous reaction of rabies vaccination.
PMID- 29333657
TI - Gelatin Methacryloyl Hydrogels in the Absence of a Crosslinker as 3D Glioblastoma
Multiforme (GBM)-Mimetic Microenvironment.
AB - 3D platforms are important for monitoring tumor progression and screening drug
candidates to eradicate tumors such as glioblastoma multiforme (GBM), a malignant
type of human brain tumor. Here, a new strategy is reported that exploits visible
light-induced crosslinking of gelatin where the reaction is carried out in the
absence of an additional crosslinker. Visible light-induced crosslinking promotes
the design of cancer microenvironment-mimetic system without compromising the
cell viability during the process and absence of crosslinker facilitates the
synthesis of the unique construct. Suspension and spheroid-based models of GBM
are used to investigate cellular behavior, expression profiles of malignancy, and
apoptosis-related genes within this unique network. Furthermore, sensitivity to
an anticancer drug, Digitoxigenin, treatment is investigated in detail. The data
suggest that U373 cells, in sparse or spheroid form, have significantly decreased
expressions of apoptosis-activating genes, Bad, Puma, and Caspase-3, and a high
expression of prosurvival Bcl-2 gene within GelMA hydrogels. Matrix
metalloproteinase genes are also upregulated within GelMA, suggesting positive
contribution of gels on extracellular remodeling of cancer cells. This unique
photocurable gelatin holds great potential for clinical translation of cancer
research through the analysis of 3D malignant cancer cell behavior, and hence for
more efficient treatment methods for GBM.
PMID- 29333659
TI - Acute renal replacement therapy during hospitalization: Is training adequate?
AB - Acute renal replacement therapy is one of the most common interventions provided
by nephrologists, however, data on the quality of training provided to nephrology
fellows is limited. Extensive curricula for acute renal replacement therapy and
the management of poisonings and intoxications have been published, but personal
experience suggests that there are significant opportunities to improve training.
Particular areas to be considered include the use of novel technologies for
assessment of volume status, greater emphasis on the dosing of medications during
acute renal replacement therapy, greater training in assessing and tailoring
treatment to the goals of care of the individual patient, incorporation of
continuous quality improvement tools into the management of acute renal
replacement therapy programs and development of robust simulation training to
augment training.
PMID- 29333658
TI - In Situ shRNA Synthesis on DNA-Polylactide Nanoparticles to Treat Multidrug
Resistant Breast Cancer.
AB - Nanomedicine has shown unprecedented potential for cancer theranostics. Nucleic
acid (e.g., DNA and RNA) nanomedicines are of particular interest for combination
therapy with chemotherapeutics. However, current nanotechnologies to construct
such nucleic acid nanomedicines, which rely on chemical conjugation or physical
complexation of nucleic acids with chemotherapeutics, have restrained their
clinical translation due to limitations such as low drug loading efficiency and
poor biostability. Herein, in situ rolling circle transcription (RCT) is applied
to synthesize short hairpin RNA (shRNA) on amphiphilic DNA-polylactide (PLA)
micelles. Core-shell PLA@poly-shRNA structures that codeliver a high payload of
doxorubicin (Dox) and multidrug resistance protein 1 (MDR1) targeted shRNA for
MDR breast cancer (BC) therapy are developed. DNA-PLA conjugates are first
synthesized, which then self-assemble into amphiphilic DNA-PLA micelles; next,
using the conjugated DNA as a promoter, poly-shRNA is synthesized on DNA-PLA
micelles via RCT, generating PLA@poly-shRNA microflowers; and finally,
microflowers are electrostatically condensed into nanoparticles using
biocompatible and multifunctional poly(ethylene glycol)-grafted polypeptides (PPT
g-PEG). These PLA@poly-shRNA@PPT-g-PEG nanoparticles are efficiently delivered
into MDR breast cancer cells and accumulated in xenograft tumors, leading to MDR1
silencing, intracellular Dox accumulation, potentiated apoptosis, and enhanced
tumor therapeutic efficacy. Overall, this nanomedicine platform is promising to
codeliver anticancer nucleic acid therapeutics and chemotherapeutics.
PMID- 29333660
TI - Interventions to increase attendance for diabetic retinopathy screening.
AB - BACKGROUND: Despite evidence supporting the effectiveness of diabetic retinopathy
screening (DRS) in reducing the risk of sight loss, attendance for screening is
consistently below recommended levels. OBJECTIVES: The primary objective of the
review was to assess the effectiveness of quality improvement (QI) interventions
that seek to increase attendance for DRS in people with type 1 and type 2
diabetes.Secondary objectives were:To use validated taxonomies of QI intervention
strategies and behaviour change techniques (BCTs) to code the description of
interventions in the included studies and determine whether interventions that
include particular QI strategies or component BCTs are more effective in
increasing screening attendance;To explore heterogeneity in effect size within
and between studies to identify potential explanatory factors for variability in
effect size;To explore differential effects in subgroups to provide information
on how equity of screening attendance could be improved;To critically appraise
and summarise current evidence on the resource use, costs and cost effectiveness.
SEARCH METHODS: We searched the Cochrane Library, MEDLINE, Embase, PsycINFO, Web
of Science, ProQuest Family Health, OpenGrey, the ISRCTN, ClinicalTrials.gov, and
the WHO ICTRP to identify randomised controlled trials (RCTs) that were designed
to improve attendance for DRS or were evaluating general quality improvement (QI)
strategies for diabetes care and reported the effect of the intervention on DRS
attendance. We searched the resources on 13 February 2017. We did not use any
date or language restrictions in the searches. SELECTION CRITERIA: We included
RCTs that compared any QI intervention to usual care or a more intensive
(stepped) intervention versus a less intensive intervention. DATA COLLECTION AND
ANALYSIS: We coded the QI strategy using a modification of the taxonomy developed
by Cochrane Effective Practice and Organisation of Care (EPOC) and BCTs using the
BCT Taxonomy version 1 (BCTTv1). We used Place of residence,
Race/ethnicity/culture/language, Occupation, Gender/sex, Religion, Education,
Socioeconomic status, and Social capital (PROGRESS) elements to describe the
characteristics of participants in the included studies that could have an impact
on equity of access to health services.Two review authors independently extracted
data. One review author entered the data into Review Manager 5 and a second
review author checked them. Two review authors independently assessed risks of
bias in the included studies and extracted data. We rated certainty of evidence
using GRADE. MAIN RESULTS: We included 66 RCTs conducted predominantly (62%) in
the USA. Overall we judged the trials to be at low or unclear risk of bias. QI
strategies were multifaceted and targeted patients, healthcare professionals or
healthcare systems. Fifty-six studies (329,164 participants) compared
intervention versus usual care (median duration of follow-up 12 months). Overall,
DRS attendance increased by 12% (risk difference (RD) 0.12, 95% confidence
interval (CI) 0.10 to 0.14; low-certainty evidence) compared with usual care,
with substantial heterogeneity in effect size. Both DRS-targeted (RD 0.17, 95% CI
0.11 to 0.22) and general QI interventions (RD 0.12, 95% CI 0.09 to 0.15) were
effective, particularly where baseline DRS attendance was low. All BCT
combinations were associated with significant improvements, particularly in those
with poor attendance. We found higher effect estimates in subgroup analyses for
the BCTs 'goal setting (outcome)' (RD 0.26, 95% CI 0.16 to 0.36) and 'feedback on
outcomes of behaviour' (RD 0.22, 95% CI 0.15 to 0.29) in interventions targeting
patients, and 'restructuring the social environment' (RD 0.19, 95% CI 0.12 to
0.26) and 'credible source' (RD 0.16, 95% CI 0.08 to 0.24) in interventions
targeting healthcare professionals.Ten studies (23,715 participants) compared a
more intensive (stepped) intervention versus a less intensive intervention. In
these studies DRS attendance increased by 5% (RD 0.05, 95% CI 0.02 to 0.09;
moderate-certainty evidence).Fourteen studies reporting any QI intervention
compared to usual care included economic outcomes. However, only five of these
were full economic evaluations. Overall, we found that there is insufficient
evidence to draw robust conclusions about the relative cost effectiveness of the
interventions compared to each other or against usual care.With the exception of
gender and ethnicity, the characteristics of participants were poorly described
in terms of PROGRESS elements. Seventeen studies (25.8%) were conducted in
disadvantaged populations. No studies were carried out in low- or middle-income
countries. AUTHORS' CONCLUSIONS: The results of this review provide evidence that
QI interventions targeting patients, healthcare professionals or the healthcare
system are associated with meaningful improvements in DRS attendance compared to
usual care. There was no statistically significant difference between
interventions specifically aimed at DRS and those which were part of a general QI
strategy for improving diabetes care. This is a significant finding, due to the
additional benefits of general QI interventions in terms of improving glycaemic
control, vascular risk management and screening for other microvascular
complications. It is likely that further (but smaller) improvements in DRS
attendance can also be achieved by increasing the intensity of a particular QI
component or adding further components.
PMID- 29333661
TI - Nanocage-Therapeutics Prevailing Phagocytosis and Immunogenic Cell Death Awakens
Immunity against Cancer.
AB - A growing appreciation of the relationship between the immune system and the
tumorigenesis has led to the development of strategies aimed at "re-editing" the
immune system to kill tumors. Here, a novel tactic is reported for overcoming the
activation-energy threshold of the immunosuppressive tumor microenvironment and
mediating the delivery and presentation of tumor neoantigens to the host's immune
system. This nature-derived nanocage not only efficiently presents ligands that
enhance cancer cell phagocytosis, but also delivers drugs that induce immunogenic
cancer cell death. The designed nanocage-therapeutics induce the release of
neoantigens and danger signals in dying tumor cells, and leads to enhancement of
tumor cell phagocytosis and cross-priming of tumor specific T cells by neoantigen
peptide-loaded antigen-presenting cells. Potent inhibition of tumor growth and
complete eradication of tumors is observed through systemic tumor-specific T cell
responses in tumor draining lymph nodes and the spleen and further, infiltration
of CD8+ T cells into the tumor site. Remarkably, after removal of the primary
tumor, all mice treated with this nanocage-therapeutics are protected against
subsequent challenge with the same tumor cells, suggesting development of
lasting, tumor-specific responses. This designed nanocage-therapeutics "awakens"
the host's immune system and provokes a durable systemic immune response against
cancer.
PMID- 29333662
TI - Serum levels of psoriasin (S100A7) and koebnerisin (S100A15) as potential markers
of atherosclerosis in patients with psoriasis.
AB - BACKGROUND: Psoriasin (S100A7) and koebnerisin (S100A15) are proinflammatory
proteins upregulated in psoriasis, but their relation to atherosclerosis remains
unclear. AIM: To evaluate the role of serum psoriasin and koebnerisin as possible
markers for subclinical atherosclerosis in patients with psoriasis. METHODS:
Serum levels of psoriasin and koebnerisin were measured by ELISA in 45 patients
with psoriasis and in 45 healthy controls (HCs). Intima-media thickness (IMT) of
the right and left common carotid arteries was measured to detect the presence of
subclinical atherosclerosis. Clinical severity of psoriasis was estimated using
the Psoriasis Area and Severity Index (PASI). RESULTS: Compared with HCs,
patients with psoriasis had significantly higher levels of psoriasin (26.61 +/-
22.45 ng/mL vs. 6.31 +/- 1.68 ng/mL, P < 0.001) and koebnerisin (21.2 +/- 13.12
ng/mL vs. 12.2 +/- 4.67 ng/mL, P = 0.001), and significantly higher IMT values
(1.07 +/- 0.4 mm vs. 0.61 +/- 0.1 mm, P < 0.001). A positive correlation was
observed between IMT and PASI (r = 0.78, P < 0.001), serum psoriasin (r = 0.48, P
> 0.01) and serum koebnerisin (r = 0.48, P < 0.01). Patients with psoriasis with
subclinical atherosclerosis had higher serum levels of koebnerisin compared with
patients without subclinical atherosclerosis (P = 0.04), which was not observed
for psoriasin (P = 0.94). CONCLUSION: Serum psoriasin and koebnerisin correlate
with IMT, underlining their value as a potential link between psoriasis and
atherosclerosis. In particular, koebnerisin seems to be a useful marker of
subclinical atherosclerosis in patients with psoriasis.
PMID- 29333663
TI - Computed tomographic retrograde positive contrast cystography and computed
tomographic excretory urography characterization of a urinary bladder
diverticulum in a dog.
AB - A one-year-old intact male German shepherd dog was referred with a 3-month
history of dysuria and pollakiuria. Physical examination revealed a large firm
mass in the caudal abdomen. Findings from survey radiography, negative contrast
cystography, computed tomographic (CT) retrograde positive contrast cystography,
and CT excretory urography were consistent with a large urinary bladder
diverticulum. An exploratory laparotomy revealed a normal wall appearance in the
ventral compartment (true bladder) and marked thinning of the wall in the dorsal
compartment (diverticulum). Both ureters inserted into the ventral compartment.
The dorsal compartment was excised and histopathology confirmed the diagnosis of
urinary bladder diverticulum.
PMID- 29333664
TI - Increased non-fatal overdose risk associated with involuntary drug treatment in a
longitudinal study with people who inject drugs.
AB - AIM: To assess the effect of involuntary drug treatment (IDT) on non-fatal
overdose among people who inject drugs (PWID). DESIGN: Longitudinal study.
SETTING: Tijuana, Mexico. PARTICIPANTS: Baseline sample of 671 PWID included 258
(38.4%) women and 413 (61.6%) men. MEASUREMENTS: Primary independent variables
were reported recent (i.e. past 6 months) non-fatal overdose event (dependent
variable) and IDT. Substance use the day of the non-fatal overdose was also
examined. FINDINGS: From 2011 to 2017, 213 participants (31.7%) reported a recent
non-fatal overdose and 103 (15.4%) reported recent IDT. Heroin, in combination
with methamphetamine and tranquilizers, were the drugs most reported at the day
of the event. IDT significantly increased the odds of reporting a non-fatal
overdose event [adjusted odds ratio (aOR) = 1.76; 95% confidence interval (CI) =
1.04-2.96]. Odds of non-fatal overdose also increased independently for each
additional injection per day (aOR = 1.05; 95% CI = 1.02-1.08), recent
tranquilizer use (aOR = 1.92; 95% CI = 1.41-2.61) and using hit doctors (aOR =
1.68; 95% CI = 1.29-2.18) and decreased with age (aOR = 0.97 per year, 95% CI =
0.95-0.99). CONCLUSIONS: Recent involuntary drug treatment in Mexico is a risk
factor for non-fatal drug overdose.
PMID- 29333667
TI - Improved Electron Transport with Reduced Contact Resistance in N-Doped Polymer
Field-Effect Transistors with a Dimeric Dopant.
AB - Attaining control on charge injection properties is significant for meaningful
applications of organic field-effect transistors (OFETs). Here, molecular
electron-doping is applied with an air-stable dimer dopant for n-type OFETs based
on (naphthalene diimide-diketopyrrolopyrrole) polymer hosts. Through
investigating the doping effect on contact and transport properties, it is found
that the electron transport increases in n-doped OFETs at low doping regime with
remaining large on/off ratios. These favorable meliorations are reconciled by the
mitigated impacts of contact resistance and interfacial traps, as well as the
surface morphology exhibiting features of increased ordering. The occurrence of
doping in the presence of dimer dopants is evidenced by the observed shift of
Fermi level toward vacuum level coupled with compositional analysis. Without
applying vacuum-deposition-based contact doping, charge injection efficiencies
are gained without losing OFET characteristics using the solution-based
methodology.
PMID- 29333665
TI - Clinical and metabolic effects associated with weight changes and obeticholic
acid in non-alcoholic steatohepatitis.
AB - BACKGROUND: In a 72-week, randomised controlled trial of obeticholic acid (OCA)
in non-alcoholic steatohepatitis (NASH), OCA was superior to placebo in improving
serum ALT levels and liver histology. OCA therapy also reduced weight. AIMS:
Because weight loss by itself can improve histology, to perform a post hoc
analysis of the effects of weight loss and OCA treatment in improving clinical
and metabolic features of NASH. METHODS: The analysis was limited to the 200
patients with baseline and end-of-treatment liver biopsies. Weight loss was
defined as a relative decline from baseline of 2% or more at treatment end.
RESULTS: Weight loss occurred in 44% (45/102) of OCA and 32% (31/98) of placebo
treated patients (P = 0.08). The NAFLD Activity score (NAS) improved more in
those with than without weight loss in both the OCA- (-2.4 vs -1.2, P<0.001) and
placebo-treated patients (-1.2 vs -0.5, P = 0.03). ALT levels also improved in
those with vs without weight loss in OCA- (-43 vs -34 U/L, P = 0.12) and placebo
treated patients (-29 vs -10 U/L, P = 0.02). However, among those who lost
weight, OCA was associated with opposite effects from placebo on changes in
alkaline phosphatase (+21 vs -12 U/L, P<0.001), total (+13 vs -14 mg/dL, P =
0.02) and LDL cholesterol (+18 vs -12 mg/dL, P = 0.01), and HbA1c (+0.1 vs -0.4%,
P = 0.01). CONCLUSIONS: OCA leads to weight loss in up to 44% of patients with
NASH, and OCA therapy and weight loss have additive benefits on serum
aminotransferases and histology. However, favourable effects of weight loss on
alkaline phosphatase, lipids and blood glucose seen in placebo-treated patients
were absent or reversed on OCA treatment. These findings stress the importance of
assessing concomitant metabolic effects of new therapies of NASH. Clinical trial
number: NCT01265498.
PMID- 29333668
TI - A photonumeric scale for the assessment of atrophic facial photodamage.
AB - BACKGROUND: Photonumeric scales have consistently shown superiority over
descriptive equivalents. They have the advantage of providing a consistent visual
frame of reference by minimizing variability in perception and subjectivity. A
photonumeric scale to assess hypertrophic facial photodamage already exists.
However, there is currently no objective measure for atrophic facial photodamage.
To address this, we have devised a nine-point photonumeric standardized scale.
OBJECTIVES: To design, test and validate a photonumeric scale for the assessment
of atrophic facial photodamage against a descriptive scale for the same
indication. METHODS: A pool of 393 facial photographs (en face and 45 degrees
oblique) from 131 individuals with atrophic facial photodamage was created. Five
photographic standards were selected and assigned grades zero through to eight,
where zero is no photodamage and eight is severe atrophic photodamage, thus
making a nine-point scale. Twenty photographs spanning the entire range of values
were selected to test the scale. Testing was performed alongside a descriptive
equivalent. A panel of 10 dermatologists, 10 nondermatology clinicians and 14
dermatology scientists marked the two scales; marking was repeated 1 week later.
RESULTS: There was a significantly greater agreement between the graders using
the photonumeric scale than the descriptive scale (kappa values 0.71 and 0.37
with standardized errors of 0.57 and 0.17, respectively) with no significant
difference in repeatability between the two methods (P < 0.05). CONCLUSIONS: The
study describes a new photonumeric scale for atrophic photodamage. This would be
a useful adjunct in both the clinical and research settings.
PMID- 29333666
TI - Stable High-Index Faceted Pt Skin on Zigzag-Like PtFe Nanowires Enhances Oxygen
Reduction Catalysis.
AB - Selectively exposing active surfaces and judiciously tuning the near-surface
composition of electrode materials represent two prominent means of promoting
electrocatalytic performance. Here, a new class of Pt3 Fe zigzag-like nanowires
(Pt-skin Pt3 Fe z-NWs) with stable high-index facets (HIFs) and nanosegregated Pt
skin structure is reported, which are capable of substantially boosting
electrocatalysis in fuel cells. These unique structural features endow the Pt
skin Pt3 Fe z-NWs with a mass activity of 2.11 A mg-1 and a specifc activity of
4.34 mA cm-2 for the oxygen reduction reaction (ORR) at 0.9 V versus reversible
hydrogen electrode, which are the highest in all reported PtFe-based ORR
catalysts. Density function theory calculations reveal a combination of exposed
HIFs and formation of Pt-skin structure, leading to an optimal oxygen adsorption
energy due to the ligand and strain effects, which is responsible for the much
enhanced ORR activities. In contrast to previously reported HIFs-based catalysts,
the Pt-skin Pt3 Fe z-NWs maintain ultrahigh durability with little activity decay
and negligible structure transformation after 50 000 potential cycles. Overcoming
a key technical barrier in electrocatalysis, this work successfully extends the
nanosegregated Pt-skin structure to nanocatalysts with HIFs, heralding the
exciting prospects of high-effcient Pt-based catalysts in fuel cells.
PMID- 29333669
TI - Blood pressure and goal titration of neurohormonal antagonists: the tortoise wins
again?
PMID- 29333670
TI - Pustular psoriasis and related pustular skin diseases.
AB - Patients with pustular psoriasis or related pustular diseases may have genetic
abnormalities impairing the function of key players of the innate skin immune
system. Recently, identification of these abnormalities has changed the paradigm
of several of these diseases. These include generalized pustular psoriasis,
palmoplantar pustular psoriasis and acrodermatitis continua of Hallopeau, and
also drug-induced acute exanthematous generalized pustular eruption. Identified
mutations in IL36RN, CARD14 and AP1S3 in different groups of patients lead to
enhanced inflammatory cascade in several cellular subtypes including
keratinocytes, and to the recruitment and activation of neutrophils and
macrophages. These insights have unveiled pathophysiological features that shift
the existing paradigms and emphasize the autoinflammatory nature of skin pustular
disorders. They also highlight the crucial role of the innate immune system
across entities belonging to the psoriasis disease spectrum, allowing
identification of new appealing therapeutic targets.
PMID- 29333671
TI - Selective enrichment of N-linked glycopeptides and glycans by using a dextran
modified hydrophilic material.
AB - Glycosylation analysis of proteins from biological sources utilizing mass
spectrometry based approaches is challenging due to the relatively low abundance
of glycopeptides, the structural diversity of glycans, and the coexisting
matrices. In this study, a customized dextran-bonded silica-based stationary
phase was introduced for selective enrichment of glycopeptides and glycans from
complex biological samples. This material has exhibited superior selectivity and
broader glycosylation site coverage over commercial Sepharose in glycoproteomic
evaluation. Additionally, the glycomic analysis of fetuin, alpha1 -acid
glycoprotein, and human serum N-glycome also indicated the relatively higher
sensitivity, selectivity, and glycoform coverage of dextran-bonded silica than
that of Sepharose and porous graphitized carbon. Therefore, the dextran-bonded
silica is expected to make contributions in the fields of glycoproteomics and
glycomics.
PMID- 29333672
TI - Controlled pattern imputation for sensitivity analysis of longitudinal binary and
ordinal outcomes with nonignorable dropout.
AB - The controlled imputation method refers to a class of pattern mixture models that
have been commonly used as sensitivity analyses of longitudinal clinical trials
with nonignorable dropout in recent years. These pattern mixture models assume
that participants in the experimental arm after dropout have similar response
profiles to the control participants or have worse outcomes than otherwise
similar participants who remain on the experimental treatment. In spite of its
popularity, the controlled imputation has not been formally developed for
longitudinal binary and ordinal outcomes partially due to the lack of a natural
multivariate distribution for such endpoints. In this paper, we propose 2
approaches for implementing the controlled imputation for binary and ordinal data
based respectively on the sequential logistic regression and the multivariate
probit model. Efficient Markov chain Monte Carlo algorithms are developed for
missing data imputation by using the monotone data augmentation technique for the
sequential logistic regression and a parameter-expanded monotone data
augmentation scheme for the multivariate probit model. We assess the performance
of the proposed procedures by simulation and the analysis of a schizophrenia
clinical trial and compare them with the fully conditional specification, last
observation carried forward, and baseline observation carried forward imputation
methods.
PMID- 29333673
TI - Predicting heart failure: one size does not fit all.
PMID- 29333675
TI - Sharing innovations to enhance renal fellow education in dialysis.
AB - Dialysis care is an integral part of the practice of nephrology. Despite this,
education of fellows in providing dialysis often remains rudimentary, relying on
a combination of didactics and learning through experience. This runs the risk of
training nephrologists who can provide dialysis care without truly being experts
on the subject. In this article, a collection of novel or innovative teaching
methods is presented that are meant to provide training programs with additional
tools with which to improve the training of their fellows in dialysis.
PMID- 29333674
TI - MicroRNA Detection by DNA-Mediated Liposome Fusion.
AB - Membrane fusion is a process of fundamental importance in biological systems that
involves highly selective recognition mechanisms for the trafficking of molecular
and ionic cargos. Mimicking natural membrane fusion mechanisms for the purpose of
biosensor development holds great potential for amplified detection because
relatively few highly discriminating targets lead to fusion and an accompanied
engagement of a large payload of signal-generating molecules. In this work,
sequence-specific DNA-mediated liposome fusion is used for the highly selective
detection of microRNA. The detection of miR-29a, a known flu biomarker, is
demonstrated down to 18 nm within 30 min with high specificity by using a
standard laboratory microplate reader. Furthermore, one order of magnitude
improvement in the limit of detection is demonstrated by using a novel imaging
technique combined with an intensity fluctuation analysis, which is coined two
color fluorescence correlation microscopy.
PMID- 29333676
TI - Ether-a-go-go K+ channels: effective modulators of neuronal excitability.
AB - Mammalian ether-a-go-go (EAG) channels are voltage-gated K+ channels. They are
encoded by the KCNH gene family and divided into three subfamilies, eag (Kv10),
erg (eag-related gene; Kv11) and elk (eag-like; Kv12). All EAG channel subtypes
are expressed in the brain where they effectively modulate neuronal excitability.
This Topical Review describes the biophysical properties of each of the EAG
channel subtypes, their function in neurons and the neurological diseases induced
by EAG channel mutations. In contrast to the function of erg currents in the
heart, where they contribute to repolarization of the cardiac action potential,
erg currents in neurons are involved in the maintenance of the resting potential,
setting of action potential threshold and frequency accommodation. They can even
support high frequency firing by preventing a depolarization-induced Na+ channel
block. EAG channels are modulated differentially, e.g. eag channels by
intracellular Ca2+ , erg channels by extracellular K+ and GPCRs, and elk channels
by changes in pH. So far, only currents mediated by erg channels have been
recorded in neurons with the help of selective blockers. Neuronal eag and elk
currents have not been isolated due to the lack of suitable channel blockers.
However, findings in KO mice indicate a physiological role of eag1 currents in
synaptic transmission and an involvement of elk2 currents in cognitive
performance. Human eag1 and eag2 gain-of-function mutations underlie syndromes
associated with epileptic seizures.
PMID- 29333679
TI - Publication ethics-Where are we today? Part 3: The good, the bad, and the ugly
face of publication.
PMID- 29333678
TI - Supplementary feeding as a source of multiresistant Salmonella in endangered
Egyptian vultures.
AB - Wild birds have repeatedly been highlighted as vectors in the dissemination of
livestock and human pathogens. Here, the occurrence, serotypes and antimicrobial
resistance of Salmonella were assessed in adult Egyptian vultures (Neophron
percnopterus), to test the hypothesis that infection is associated with the
consumption of swine carcasses provided at supplementary feeding stations (SFSs).
Faeces of year-round resident griffon vultures (Gyps fulvus) were also tested to
assess whether infection was acquired in the breeding grounds of both species or
in the African wintering quarters of Egyptian vultures. Depending on the shedding
rate criteria considered, the occurrence of infection in Egyptian vultures varied
between the three consecutive sampling days in a range with a minimum of 23%-41%
and a maximum of 64%-92% of individuals (n = 11-14 individuals, 27-39 faeces).
The occurrence in the single sampling of griffon vultures was 61% of faeces (n =
18). Vultures mostly fed on pig carcasses, which together with their predominant
infection with multiresistant serotypes (mostly the monophasic 4,12:i:- variant
resistant to aminopenicillins, aminoglycosides and tetracyclines) typically found
in pigs from Spain, strongly supports a carcass-to-vulture transmission and cross
infection routes at SFSs. Efforts are encouraged to avoid discarding carcasses of
pigs with Salmonella at SFSs established for the conservation of threatened
scavengers. This could contribute to reducing the long-distance transmission of
resistant pathogens with an impact on livestock and human health while avoiding
infection risk and its effects on wildlife.
PMID- 29333677
TI - Diminished alternative reinforcement as a mechanism linking conduct problems and
substance use in adolescence: a longitudinal examination.
AB - AIMS: To determine whether diminished alternative reinforcement (i.e. engagement
and enjoyment from substance-free activities) mediated the longitudinal
association of conduct problems with substance use in early-mid-adolescence.
DESIGN: Structural equation modeling tested whether the association between wave
1 (baseline) conduct problems and wave 3 (24-month follow-up) substance use
outcomes was mediated by diminished alternative reinforcement at wave 2 (12-month
follow-up). Additional analyses tested whether sex and socio-economic status
moderated this association. SETTING: Ten high schools in Los Angeles, CA, USA,
2013-15. PARTICIPANTS: Students (n = 3396, 53.5% female, mean [standard deviation
(SD)] age at wave 1 baseline = 14.1 (0.42) years). MEASUREMENTS: Self-reported
conduct problems (11-item questionnaire), alternative reinforcement (44-item
questionnaire) and use of alcohol, marijuana and combustible cigarettes during
the past 6 months (yes/no) and the past 30 days (nine-level ordinal response
based on days used in past 30 days). RESULTS: Significant associations of wave 1
conduct problems with wave 3 marijuana use during the past 6 months (beta = 0.25)
and past 30 days (beta = 0.26) were mediated by wave 2 diminished alternative
reinforcement (betaindirect effect : 6 months = 0.013, 30 days = 0.017, Ps <
0.001). Associations of conduct problems with alcohol or combustible cigarette
use were not mediated by alternative reinforcement. All associations did not
differ by sex and socio-economic status. CONCLUSIONS: Diminished alternative
reinforcement may be a modifiable mechanism linking early adolescent conduct
problems and subsequent marijuana use that could be targeted in prevention
programs to offset the adverse health and social sequelae associated with
comorbid conduct problems and marijuana use in early-mid adolescence.
PMID- 29333680
TI - Cellulose-Based Biomimetics and Their Applications.
AB - Nature has been producing cellulose since long before man walked the surface of
the earth. Millions of years of natural design and testing have resulted in
cellulose-based structures that are an inspiration for the production of
synthetic materials based on cellulose with properties that can mimic natural
designs, functions, and properties. Here, five sections describe cellulose-based
materials with characteristics that are inspired by gratings that exist on the
petals of the plants, structurally colored materials, helical filaments produced
by plants, water-responsive materials in plants, and environmental stimuli
responsive tissues found in insects and plants. The synthetic cellulose-based
materials described herein are in the form of fibers and films. Fascinating
multifunctional materials are prepared from cellulose-based liquid crystals and
from composite cellulosic materials that combine functionality with structural
performance. Future and recent applications are outlined.
PMID- 29333681
TI - Myotropic activity and immunolocalization of selected neuropeptides of the
burying beetle Nicrophorus vespilloides (Coleoptera: Silphidae).
AB - Burying beetles (Nicrophorus sp.) are necrophagous insects with developed
parental care. Genome of Nicrophorus vespilloides has been recently sequenced,
which makes them interesting model organism in behavioral ecology. However, we
know very little about their physiology, including the functioning of their
neuroendocrine system. In this study, one of the physiological activities of
proctolin, myosuppressin (Nicve-MS), myoinhibitory peptide (Trica-MIP-5) and the
short neuropeptide F (Nicve-sNPF) in N. vespilloides have been investigated. The
tested neuropeptides were myoactive on N. vespilloides hindgut. After application
of the proctolin increased hindgut contraction frequency was observed (EC50 value
was 5.47 * 10-8 mol/L). The other tested neuropeptides led to inhibition of N.
vespilloides hindgut contractions (Nicve-MS: IC50 = 5.20 * 10-5 mol/L; Trica-MIP
5: IC50 = 5.95 * 10-6 mol/L; Nicve-sNPF: IC50 = 4.08 * 10-5 mol/L). Moreover, the
tested neuropeptides were immunolocalized in the nervous system of N.
vespilloides. Neurons containing sNPF and MIP in brain and ventral nerve cord
(VNC) were identified. Proctolin-immunolabeled neurons only in VNC were observed.
Moreover, MIP-immunolabeled varicosities and fibers in retrocerebral complex were
observed. In addition, our results have been supplemented with alignments of
amino acid sequences of these neuropeptides in beetle species. This alignment
analysis clearly showed amino acid sequence similarities between neuropeptides.
Moreover, this allowed to deduce amino acid sequence of N. vespilloides proctolin
(RYLPTa), Nicve-MS (QDVDHVFLRFa) and six isoforms of Nicve-MIP (Nicve-MIP-1
DWNRNLHSWa; Nicve-MIP-2-AWQNLQGGWa; Nicve-MIP-3-AWQNLQGGWa; Nicve-MIP-4
AWKNLNNAGWa; Nicve-MIP-5-SEWGNFRGSWa; Nicve-MIP-6- DPAWTNLKGIWa; and Nicve-sNPF
SGRSPSLRLRFa).
PMID- 29333682
TI - Selective extraction of bisphenol A from water by one-monomer molecularly
imprinted magnetic nanoparticles.
AB - One-monomer molecularly imprinted magnetic nanoparticles were prepared as
adsorbents for selective extraction of bisphenol A from water in this study. A
single bi-functional monomer was adopted for preparation of the molecularly
imprinted polymer, avoiding the tedious trial-and-error optimizations as
traditional strategy. Moreover, bisphenol F was used as the dummy template for
bisphenol A to avoid the interference from residual template molecules. These
nanoparticles showed not only large adsorption capacity and good selectivity to
the bisphenol A but also outstanding magnetic response performance. Furthermore,
they were successfully used as magnetic solid-phase extraction adsorbents of
bisphenol A from various water samples, including tap water, river water, and
seawater. The developed method was found to be much more efficient, convenient,
and economical for selective extraction of bisphenol A compared with the
traditional solid-phase extraction. Separation of these nanoparticles can be
easily achieved with an external magnetic field, and the optimized adsorption
time was only 15 min. The recoveries of bisphenol A in different water samples
ranged from 85.38 to 93.75%, with relative standard deviation lower than 7.47%.
These results showed that one-monomer molecularly imprinted magnetic
nanoparticles had the potential to be popular adsorbents for selective extraction
of pollutants from water.
PMID- 29333683
TI - Mobility Engineering in Vertical Field Effect Transistors Based on Van der Waals
Heterostructures.
AB - Vertical integration of 2D layered materials to form van der Waals
heterostructures (vdWHs) offers new functional electronic and optoelectronic
devices. However, the mobility in vertical carrier transport in vdWHs of vertical
field-effect transistor (VFET) is not yet investigated in spite of the importance
of mobility for the successful application of VFETs in integrated circuits. Here,
the mobility in VFET of vdWHs under different drain biases, gate biases, and
metal work functions is first investigated and engineered. The traps in WSe2 are
the main source of scattering, which influences the vertical mobility and three
distinct transport mechanisms: Ohmic transport, trap-limited transport, and space
charge-limited transport. The vertical mobility in VFET can be improved by
suppressing the trap states by raising the Fermi level of WSe2 . This is achieved
by increasing the injected carrier density by applying a high drain voltage, or
decreasing the Schottky barrier at the graphene/WSe2 and metal/WSe2 junctions by
applying a gate bias and reducing the metal work function, respectively.
Consequently, the mobility in Mn vdWH at +50 V gate voltage is about 76 times
higher than the initial mobility of Au vdWH. This work enables further
improvements in the VFET for successful application in integrated circuits.
PMID- 29333684
TI - Biocatalytic Synthesis of Nitriles through Dehydration of Aldoximes: The
Substrate Scope of Aldoxime Dehydratases.
AB - Nitriles, which are mostly needed and produced by the chemical industry, play a
major role in various industry segments, ranging from high-volume, low-price
sectors, such as polymers, to low-volume, high-price sectors, such as chiral
pharma drugs. A common industrial technology for nitrile production is
ammoxidation as a gas-phase reaction at high temperature. Further popular
approaches are substitution or addition reactions with hydrogen cyanide or
derivatives thereof. A major drawback, however, is the very high toxicity of
cyanide. Recently, as a synthetic alternative, a novel enzymatic approach towards
nitriles has been developed with aldoxime dehydratases, which are capable of
converting an aldoxime in one step through dehydration into nitriles. Because the
aldoxime substrates are easily accessible, this route is of high interest for
synthetic purposes. However, whenever a novel method is developed for organic
synthesis, it raises the question of substrate scope as one of the key criteria
for application as a "synthetic platform technology". Thus, the scope of this
review is to give an overview of the current state of the substrate scope of this
enzymatic method for synthesizing nitriles with aldoxime dehydratases. As a
recently emerging enzyme class, a range of substrates has already been studied so
far, comprising nonchiral and chiral aldoximes. This enzyme class of aldoxime
dehydratases shows a broad substrate tolerance and accepts aliphatic and aromatic
aldoximes, as well as arylaliphatic aldoximes. Furthermore, aldoximes with a
stereogenic center are also recognized and high enantioselectivities are found
for 2-arylpropylaldoximes, in particular. It is further noteworthy that the
enantiopreference depends on the E and Z isomers. Thus, opposite enantiomers are
accessible from the same racemic aldehyde and the same enzyme.
PMID- 29333685
TI - Co(OH)2 Nanoparticle-Encapsulating Conductive Nanowires Array: Room-Temperature
Electrochemical Preparation for High-Performance Water Oxidation
Electrocatalysis.
AB - It is highly desired but still remains challenging to design and develop a Co
based nanoparticle-encapsulated conductive nanoarray at room temperature for high
performance water oxidation electrocatalysis. Here, it is reported that room
temperature anodization of a Co(TCNQ)2 (TCNQ = tetracyanoquinodimethane) nanowire
array on copper foam at alkaline pH leads to in situ electrochemcial oxidation of
TCNQ- into water-insoluable TCNQ nanoarray embedding Co(OH)2 nanoparticles. Such
Co(OH)2 -TCNQ/CF shows superior catalytic activity for water oxidation and
demands only a low overpotential of 276 mV to drive a geometrical current density
of 25 mA cm-2 in 1.0 m KOH. Notably, it also demonstrates strong long-term
electrochemical durability with its activity being retrained for at least 25 h, a
high turnover frequency of 0.97 s-1 at an overpotential of 450 mV and 100%
Faradic efficiency. This study provides an exciting new method for the rational
design and development of a conductive TCNQ-based nanoarray as an interesting 3D
material for advanced electrochemical applications.
PMID- 29333686
TI - Predicting hypertension among Korean cancer survivors: A nationwide population
based study.
AB - Hypertension is the most common comorbidity among cancer survivors, although
there is no model for predicting hypertension in this population. Therefore, we
developed a model for predicting hypertension using data from 6,480 Korean cancer
survivors who were >=20 years old. The odds ratios (ORs) for hypertension were
calculated using stepwise logistic regression analyses, and a nomogram was
generated to predict hypertension. Hypertension was independently associated with
an age of >=65 years (OR: 3.058), male gender (OR: 1.195), obesity (OR: 1.998),
prehypertension (OR: 2.06), dyslipidaemia (OR: 2.011) and diabetes mellitus (OR:
2.297). Each variable in the nomogram was assigned a specific number of points,
and the total score (range: 0-400) was used to obtain a value for predicting
hypertension. The estimated prevalence of hypertension increased when the total
nomogram score exceeded the sixth decile (total points: 128; p for trend <.001).
Therefore, among Korean cancer survivors, hypertension was significantly
associated with an age of >65 years, male gender, obesity, and having various
comorbidities (e.g., prehypertension, dyslipidaemia and diabetes mellitus).
Furthermore, our nomogram could predict the incidence of hypertension, and the
sixth decile of the total nomogram score predicted an increased risk of
hypertension.
PMID- 29333687
TI - H9N2 influenza virus isolated from minks has enhanced virulence in mice.
AB - H9N2 is one of the major subtypes of influenza virus circulating in poultry in
China, which has a wide host range from bird to mammals. Two H9N2 viruses were
isolated from one mink farm in 2014. Phylogenetic analysis showed that internal
genes of the H9N2 viruses have close relationship with those of H7N9 viruses.
Interestingly, two H9N2 were separated in phylogenetic trees, indicating that
they are introduced to this mink farm in two independent events. And further mice
studies showed that one H9N2 caused obvious weight loss and 20% mortality in
infected mice, while another virus did not cause any clinical sign in mice
infected at the same dose. Genetic analysis indicated that the virulent H9N2
contain a natural mutation at 701N in PB2 protein, which was reported to
contribute to mammalian adaptation. However, such substitution is absent in the
H9N2 avirulent to mice. Circulation of H9N2 in mink may drive the virus to adapt
mammals; continual surveillance of influenza virus in mink was warranted.
PMID- 29333689
TI - 2D-Black-Phosphorus-Reinforced 3D-Printed Scaffolds:A Stepwise Countermeasure for
Osteosarcoma.
AB - With the ever-deeper understanding of nano-bio interactions and the development
of fabrication methodologies of nanomaterials, various therapeutic platforms
based on nanomaterials have been developed for next-generation oncological
applications, such as osteosarcoma therapy. In this work, a black phosphorus (BP)
reinforced 3D-printed scaffold is designed and prepared to provide a feasible
countermeasure for the efficient localized treatment of osteosarcoma. The in situ
phosphorus-driven, calcium-extracted biomineralization of the intra-scaffold BP
nanosheets enables both photothermal ablation of osteosarcoma and the subsequent
material-guided bone regeneration in physiological microenvironment, and in the
meantime endows the scaffolds with unique physicochemical properties favoring the
whole stepwise therapeutic process. Additionally, a corrugated structure
analogous to Haversian canals is found on newborn cranial bone tissue of Sprague
Dawley rats, which may provide much inspiration for the future research of bone
tissue engineering.
PMID- 29333688
TI - Infant brain responses to felt and observed touch of hands and feet: an MEG
study.
AB - There is growing interest concerning the ways in which the human body, both one's
own and that of others, is represented in the developing human brain. In two
experiments with 7-month-old infants, we employed advances in infant
magnetoencephalography (MEG) brain imaging to address novel questions concerning
body representations in early development. Experiment 1 evaluated the
spatiotemporal organization of infants' brain responses to being touched. A
punctate touch to infants' hands and feet produced significant activation in the
hand and foot areas of contralateral primary somatosensory cortex as well as in
other parietal and frontal areas. Experiment 2 explored infant brain responses to
visually perceiving another person's hand or foot being touched. Results showed
significant activation in early visual regions and also in regions thought to be
involved in multisensory body and self-other processing. Furthermore, observed
touch of the hand and foot activated the infant's own primary somatosensory
cortex, although less consistently than felt touch. These findings shed light on
aspects of early social cognition, including action imitation, which may build,
at least in part, on infant neural representations that map equivalences between
the bodies of self and other.
PMID- 29333690
TI - High-Capacity Cathode Material with High Voltage for Li-Ion Batteries.
AB - Electrochemical energy storage devices with a high energy density are an
important technology in modern society, especially for electric vehicles. The
most effective approach to improve the energy density of batteries is to search
for high-capacity electrode materials. According to the concept of energy
quality, a high-voltage battery delivers a highly useful energy, thus providing a
new insight to improve energy density. Based on this concept, a novel and
successful strategy to increase the energy density and energy quality by
increasing the discharge voltage of cathode materials and preserving high
capacity is proposed. The proposal is realized in high-capacity Li-rich cathode
materials. The average discharge voltage is increased from 3.5 to 3.8 V by
increasing the nickel content and applying a simple after-treatment, and the
specific energy is improved from 912 to 1033 Wh kg-1 . The current work provides
an insightful universal principle for developing, designing, and screening
electrode materials for high energy density and energy quality.
PMID- 29333692
TI - Measuring spatial and temporal trends of nicotine and alcohol consumption in
Australia using wastewater-based epidemiology.
AB - BACKGROUND AND AIMS: Tobacco and alcohol consumption remain priority public
health issues world-wide. As participation in population-based surveys has
fallen, it is increasingly challenging to estimate accurately the prevalence of
alcohol and tobacco use. Wastewater-based epidemiology (WBE) is an alternative
approach for estimating substance use at the population level that does not rely
upon survey participation. This study examined spatio-temporal patterns in
nicotine (a proxy for tobacco) and alcohol consumption in the Australian
population via WBE. METHODS: Daily wastewater samples (n = 164) were collected at
18 selected wastewater treatment plants across Australia, covering approximately
45% of the total population. Nicotine and alcohol metabolites in the samples were
measured using liquid chromatography-tandem mass spectrometry. Daily consumption
of nicotine and alcohol and its associated uncertainty were computed using Monte
Carlo simulations. Nation-wide daily average and weekly consumption of these two
substances were extrapolated using ordinary least squares and mixed-effect
models. FINDINGS: Nicotine and alcohol consumption was observed in all
communities. Consumption of these substances in rural towns was three to four
times higher than in urban communities. The spatial consumption pattern of these
substances was consistent across the monitoring periods in 2014-15. Nicotine
metabolites significantly reduced by 14-25% (P = 0.001-0.008) (2014-15) in some
catchments. Alcohol consumption remained constant over the studied periods.
Strong weekly consumption patterns were observed for alcohol but not nicotine.
Nation-wide, the daily average consumption per person (aged 15-79 years) was
estimated at approximately 2.5 cigarettes and 1.3-2.0 standard drinks (weekday
weekend) of alcohol. These estimates were close to the sale figure and apparent
consumption, respectively. CONCLUSIONS: Wastewater-based epidemiology is a
feasible method for objectively evaluating the geographic, temporal and weekly
profiles of nicotine and alcohol consumption in different communities nationally.
PMID- 29333693
TI - Polypeptide Polymer Brushes by Light-Induced Surface Polymerization of Amino Acid
N-Carboxyanhydrides.
AB - Silicon wafers are decorated with photoamine generator 4,5-dimethoxy-2
nitrobenzyl 3-(triethoxysilyl)propyl carbamate. UV-irradiation in the presence of
benzyl-l-glutamate N-carboxyanhydride is carried out, resulting in the release of
the surface-bound primary amines, making them viable N-carboxyanhydride (NCA)
polymerization initiators. Successful polypeptide grafting is confirmed by water
contact angle measurements as well as by ellipsometry, revealing a poly(benzyl-l
glutamate) (PBLG) layer of ~3 nm. X-ray photoelectron spectroscopy confirms the
presence of amide groups in the grafted PBLG while time-of-flight secondary ion
mass spectroscopy provides additional evidence for the presence of PBLG on the
surface. Evaluation of negative control samples confirms successful UV surface
grafting. The approach is thus established as a viable general method for light
exposure directable polypeptide functionalization of silicon surfaces.
PMID- 29333695
TI - FCI Literature Prize: T. Schirmeister, C. Schmuck, P. R. Wich / Foundation for
Polish Science Award: D. T. Gryko / Heinz Award: J. M. DeSimone.
PMID- 29333694
TI - Chemical Composition Fractionation of Olefin Plastomers/Elastomers by Solvent and
Thermal Gradient Interaction Chromatography.
AB - Olefin plastomers/elastomers are typically copolymers with high comonomer
contents and low crystallinities. Therefore, the fractionation of these materials
with crystallization-based methods is not feasible. On the other hand, solvent
and temperature gradient interaction chromatography (SGIC and TGIC, respectively)
are suitable techniques for the separation of olefin copolymers with regard to
their chemical composition. In this study, the application ranges of both
techniques are investigated and compared for ethylene-propylene (EP) copolymers.
A linear dependency of ethylene content versus elution volume is obtained with
SGIC in practically the whole ethylene range. In the case of TGIC, a linear
dependency is obtained within certain ethylene content limits. The accessible
ethylene content separation range for TGIC is 50-100 mol% ethylene, and a broader
26-100 mol% ethylene range is accessible for SGIC, the latter being the technique
of choice in the analysis of EP rubbers.
PMID- 29333691
TI - The innate immune system in chronic cardiomyopathy: a European Society of
Cardiology (ESC) scientific statement from the Working Group on Myocardial
Function of the ESC.
AB - Activation of the immune system in heart failure (HF) has been recognized for
over 20 years. Initially, experimental studies demonstrated a maladaptive role of
the immune system. However, several phase III trials failed to show beneficial
effects in HF with therapies directed against an immune activation. Preclinical
studies today describe positive and negative effects of immune activation in HF.
These different effects depend on timing and aetiology of HF. Therefore, herein
we give a detailed review on immune mechanisms and their importance for the
development of HF with a special focus on commonalities and differences between
different forms of cardiomyopathies. The role of the immune system in ischaemic,
hypertensive, diabetic, toxic, viral, genetic, peripartum, and autoimmune
cardiomyopathy is discussed in depth. Overall, initial damage to the heart leads
to disease specific activation of the immune system whereas in the chronic phase
of HF overlapping mechanisms occur in different aetiologies.
PMID- 29333696
TI - The Plantain Proteome, a Focus on Allele Specific Proteins Obtained from Plantain
Fruits.
AB - Proteomics has been applied with great potential to elucidate molecular
mechanisms in plants. This is especially valid in the case of non-model crops of
which their genome has not been sequenced yet, or is not well annotated.
Plantains are a kind of cooking bananas that are economically very important in
Africa, India, and Latin America. The aim of this work was to characterize the
fruit proteome of common dessert bananas and plantains and to identify proteins
that are only encoded by the plantain genome. We present the first plantain fruit
proteome. All data are available via ProteomeXchange with identifier PXD005589.
Using our in-house workflow, we found 37 alleles to be unique for plantain
covered by 59 peptides. Although we do not have access (yet) to whole-genome
sequencing data from triploid banana cultivars, we show that proteomics is an
easily accessible complementary alternative to detect different allele specific
SNPs/SAAPs. These unique alleles might contribute toward the differences in the
metabolism between dessert bananas and plantains. This dataset will stimulate
further analysis by the scientific community, boost plantain research, and
facilitate plantain breeding.
PMID- 29333697
TI - Lactic Acid Bacteria May Impact Intestinal Barrier Function by Modulating Goblet
Cells.
AB - SCOPE: Lactic acid bacteria (LAB) are recognized to promote gastrointestinal
health by mechanisms that are not fully understood. LABs might modulate the mucus
and thereby enhance intestinal barrier function. Herein, we investigate effects
of different LAB strains and species on goblet cell genes involved in mucus
synthesis. METHODS AND RESULTS: Gene expression profiles of goblet-cell
associated products (mucin MUC2, trefoil factor 3, resistin-like molecule beta,
carbohydrate sulfotransferase 5, and galactose-3-O-sulfotransferase 2) induced by
LAB or their derived conditioned medium in human goblet cell line LS174T are
studied. Effects of LAB on gene transcription are assessed with or without
exposure to TNF-alpha, IL-13, or the mucus damaging agent tunicamycin. LAB do
impact the related genes in a species- and strain-specific fashion and their
effects are different in the presence of the cytokines and tunicamycin. Bioactive
factors secreted by some strains are also found to regulate goblet cell-related
genes. CONCLUSION: Our findings provide novel insights in differences in
modulatory efficacy on mucus genes between LAB species and strains. This study
further unravels direct interactions between LAB and intestinal goblet cells, and
highlights the importance of rationally selecting appropriate LAB candidates to
achieve specific benefits in the gut.
PMID- 29333698
TI - Design of Enzyme Micelles with Controllable Concavo-Convex Micromorphologies for
Highly Enhanced Stability and Catalytical Activity.
AB - Concavo-convex micelles with controllable sizes and nanostructures are prepared
via self-assembling polymer-enzyme (e.g., shellac enzyme) conjugates with
heterogeneous polymer chains, which exhibit higher enzyme stability (300%) and
bioactivity (760%) comparing with the well-defined ones. The applied amphiphilic
and negatively charged copolymer, poly (methyl methacrylate)-block-poly (sodium p
styrene sulfonate), is synthesized via reversible addition-fragmentation chain
transfer polymerization to modify shellac enzyme and immobilize the enzyme
bioactivity inducer by covalent conjugation and electrostatic attraction,
respectively. The degradation test of catechol confirms the application potential
of as-prepared micelles as an efficient and economical decontaminant.
PMID- 29333699
TI - Pomegranate-Structured Silica/Sulfur Composite Cathodes for High-Performance
Lithium-Sulfur Batteries.
AB - Porous materials have many structural advantages for energy storage and
conversion devices such as rechargeable batteries, supercapacitors, and fuel
cells. When applied as a host material in lithium-sulfur batteries, porous silica
materials with a pomegranate-like architecture can not only act as a buffer
matrix for accommodating a large volume change of sulfur, but also suppress the
polysulfide shuttle effect. The porous silica/sulfur composite cathodes exhibit
excellent electrochemical performances including a high specific capacity of 1450
mA h g-1 , a reversible capacity of 82.9 % after 100 cycles at a rate of C/2 (1
C=1672 mA g-1 ) and an extended cyclability over 300 cycles at 1 C-rate.
Furthermore, the high polysulfide adsorption property of porous silica has been
proven by ex-situ analyses, showing a relationship between the surface area of
silica and polysulfide adsorption ability. In particular, the modified porous
silica/sulfur composite cathode, which is treated by a deep-lithiation process in
the first discharge step, exhibits a highly reversible capacity of 94.5 % at 1C
rate after 300 cycles owing to a formation of lithiated-silica frames and stable
solid-electrolyte-interphase layers.
PMID- 29333700
TI - Understanding Australian medical student attitudes towards older people.
AB - OBJECTIVE: The aim of this article was to review the literature around Australian
medical student attitudes towards older people. METHODS: An Ovid cross-search and
SCOPUS search were performed using keywords such as 'Attitude', 'Medical Student'
and 'Aged or Older or Elderly'. RESULTS: Several recent studies have investigated
the attitudes of Australian medical students towards older people. Baseline
attitudes at two medical schools were positive. Three studies quantified attitude
improvement after curriculum intervention. All the studies used US-developed
instruments, which have not been validated in Australia. Qualitative studies have
described mixed attitudes towards older people: negative themes included
nihilism, paternalism, communication issues, greater morbidity and reduced
quality of life. Positively, students placed value on clinical decision-making
and critical reflection during residential aged care placements. CONCLUSION:
Australian medical students' attitudes towards older people are mixed and not
well understood based on quantitative measures developed for use in the US and on
qualitative evidence. Future research in this area requires a reliable and
locally-validated instrument.
PMID- 29333701
TI - The Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment
Plans: Toward Comparative Effectiveness in the Pediatric Rheumatic Diseases.
AB - The pediatric rheumatic diseases are a heterogeneous group of rare diseases,
posing a number of challenges for the use of traditional clinical and
translational research methods. Innovative comparative effectiveness approaches
are needed to efficiently study treatment strategies and disease outcomes. The
Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed the
consensus treatment plan (CTP) approach as a comparative effectiveness tool for
research in pediatric rheumatology. CTPs are treatment strategies, developed by
consensus methods among CARRA members, intended to reduce variation in treatment
approaches, standardize outcome measurements, and allow for comparison of the
effectiveness of different approaches with the goal of improving disease
outcomes. To date, CTPs have been published for 8 different diseases and disease
manifestations. The approach has been successfully piloted for juvenile localized
scleroderma, systemic juvenile idiopathic arthritis (JIA), polyarticular JIA,
dermatomyositis, and lupus nephritis. Large-scale studies are underway for
systemic JIA and polyarticular JIA, with the CARRA patient registry serving as
the data collection platform. These studies have been designed with stakeholder
involvement, including active input from CARRA providers, patients, and parents,
with the goal of increasing feasibility and ensuring the relevance of the
outcomes. These studies include ancillary biologic specimen collection intended
to support additional translational and mechanistic studies. Data from these
ongoing CTP studies will provide more information on the ability of this approach
to identify effective treatment strategies and improve outcomes in the pediatric
rheumatic diseases.
PMID- 29333702
TI - MAML1 and TWIST1 co-overexpression promote invasion of head and neck squamous
cell carcinoma.
AB - AIMS: Head and neck squamous cell carcinoma (HNSCC) is the seventh most common
cancer worldwide with considerable morbidity and mortality. Invasion and
metastasis of HNSCC is a complex process involving multiple molecules and
signaling pathways. Twist Family BHLH Transcription Factor 1 (TWIST1) and
Mastermind-like 1 (MAML1) are essential in induction of epithelial-mesenchymal
transition through direct regulation of implicated molecules in cellular
adhesion, migration and invasion. Our aim in this study was to assess the
clinical significance of MAML1 and TWIST1 expression in HNSCC, and elucidate the
probable correlation between these genes to exhibit their possible associations
with progression and metastasis of the disease. METHODS: The gene expression
profile of MAML1 and TWIST1 was assessed in fresh tumoral compared to distant
tumor-free tissues of 55 HNSCC patients using quantitative real-time Polymerase
chain reaction (PCR). RESULTS: Significant overexpression of MAML1 and TWIST1
mRNA was observed in 49.1% and 38.2% (P ? 0.05) of tumor specimens, respectively.
Overexpression of MAML1 was associated with vascular invasion (P = 0.048).
Concomitant overexpression of MAML1 and TWIST1 was significantly correlated to
each other (P = 0.004). Co-overexpression of the genes was significantly
correlated to the various clinicopathological indices of poor prognosis including
depth of tumor invasion (P < 0.01), lymphatic invasion and grade of tumor cell
differentiation (P < 0.05). CONCLUSIONS: Significant correlation between MAML1
and TWIST1 in HNSCC was revealed. This study was the first report elucidating
MAML1 clinical relevance in HNSCC. These new findings suggest an oncogenic role
for concomitant expression of MAML1 and TWIST1 genes in HNSCC invasion and
metastasis.
PMID- 29333703
TI - Clinical aspects of diabetes in pregnancy.
PMID- 29333704
TI - Asian horses deepen the MSY phylogeny.
AB - Humans have shaped the population history of the horse ever since domestication
about 5500 years ago. Comparative analyses of the Y chromosome can illuminate the
paternal origin of modern horse breeds. This may also reveal different breeding
strategies that led to the formation of extant breeds. Recently, a horse Y
chromosomal phylogeny of modern horses based on 1.46 Mb of the male-specific Y
(MSY) was generated. We extended this dataset with 52 samples from five European,
two American and seven Asian breeds. As in the previous study, almost all modern
European horses fall into a crown group, connected via a few autochthonous
Northern European lineages to the outgroup, the Przewalski's Horse. In total, we
now distinguish 42 MSY haplotypes determined by 158 variants within domestic
horses. Asian horses show much higher diversity than previously found in European
breeds. The Asian breeds also introduce a deep split to the phylogeny,
preliminarily dated to 5527 +/- 872 years. We conclude that the deep splitting
Asian Y haplotypes are remnants of a far more diverse ancient horse population,
whose haplotypes were lost in other lineages.
PMID- 29333706
TI - Estimating the footprint of pollution on coral reefs with models of species
turnover.
AB - Ecological communities typically change along gradients of human impact, although
it is difficult to estimate the footprint of impacts for diffuse threats such as
pollution. We developed a joint model (i.e., one that includes multiple species
and their interactions with each other and environmental covariates) of benthic
habitats on lagoonal coral reefs and used it to infer change in benthic
composition along a gradient of distance from logging operations. The model
estimated both changes in abundances of benthic groups and their compositional
turnover, a type of beta diversity. We used the model to predict the footprint of
turbidity impacts from past and recent logging. Benthic communities far from
logging were dominated by branching corals, whereas communities close to logging
had higher cover of dead coral, massive corals, and soft sediment. Recent impacts
were predicted to be small relative to the extensive impacts of past logging
because recent logging has occurred far from lagoonal reefs. Our model can be
used more generally to estimate the footprint of human impacts on ecosystems and
evaluate the benefits of conservation actions for ecosystems.
PMID- 29333705
TI - A Light Harvesting, Self-Powered Monolith Tactile Sensor Based on Electric Field
Induced Effects in MAPbI3 Perovskite.
AB - Organolead trihalide perovskite MAPbI3 shows a distinctive combination of
properties such as being ferroelectric and semiconducting, with ion migration
effects under poling by electric fields. The combination of its ferroelectric and
semiconducting nature is used to make a light harvesting, self-powered tactile
sensor. This sensor interfaces ZnO nanosheets as a pressure-sensitive drain on
the MAPbI3 film and once poled is operational for at least 72 h with just light
illumination. The sensor is monolithic in structure, has linear response till 76
kPa, and is able to operate continuously as the energy harvesting mechanism is
decoupled from its pressure sensing mechanism. It has a sensitivity of 0.57 kPa-1
, which can be modulated by the strength of the poling field. The understanding
of these effects in perovskite materials and their application in power source
free devices are of significance to a wide array of fields where these materials
are being researched and applied.
PMID- 29333707
TI - Impact of Gastric Acid Induced Surface Changes on Mechanical Behavior and Optical
Characteristics of Dental Ceramics.
AB - PURPOSE: To test the impact of exposure to artificial gastric acid combined with
toothbrush abrasion on the properties of dental ceramics. Earlier research has
indicated that immersion in artificial gastric acid has caused increased surface
roughness of dental ceramics; however, the combined effects of acid immersion and
toothbrush abrasion and the impact of increased surface roughness on mechanical
strength and optical properties have not been studied. MATERIALS AND METHODS:
Three commercially available ceramics were chosen for this study: feldspathic
porcelain, lithium disilicate glass-ceramic, and monolithic zirconium oxide. The
specimens (10 * 1 mm discs) were cut, thermally treated as required, and
polished. Each material was divided into four groups (n = 8 per group): control
(no exposure), acid only, brush only, acid + brush. The specimens were immersed
in artificial gastric acid (50 ml of 0.2% [w/v] sodium chloride in 0.7% [v/v]
hydrochloric acid mixed with 0.16 g of pepsin powder, pH = 2) for 2 minutes and
rinsed with deionized water for 2 minutes. The procedure was repeated 6 times/day
* 9 days, and specimens were stored in deionized water at 37 degrees C.
Toothbrush abrasion was performed using an ISO/ADA design brushing machine for
100 cycles/day * 9 days. The acid + brush group received both treatments.
Specimens were examined under SEM and an optical microscope for morphological
changes. Color and translucency were measured using spectrophotometer CIELAB
coordinates (L*, a*, b*). Surface gloss was measured using a gloss meter. Surface
roughness was measured using a stylus profilometer. Biaxial flexural strength was
measured using a mechanical testing machine. The data were analyzed by one-way
ANOVA followed by Tukey's HSD post hoc test (p < 0.05). RESULTS: Statistically
significant changes were found for color, gloss, and surface roughness for
porcelain and e.max specimens. No statistically significant changes were found
for any properties of zirconia specimens. CONCLUSIONS: The acid treatment
affected the surface roughness, color, and gloss of porcelain and e.max ceramics.
The changes in translucency and mechanical strength for all materials were not
statistically significant. Zirconia ceramic showed resistance to all treatments.
PMID- 29333709
TI - The 'airway spider': an education tool to assist teaching human factors and
ergonomics in airway management.
PMID- 29333708
TI - Difficult mask ventilation and muscle relaxation.
PMID- 29333710
TI - Mechanical ventilation mode and postoperative pulmonary complications - a reply.
PMID- 29333711
TI - Double-blind and single-blind retractable placebo needles.
PMID- 29333712
TI - Comparing bougie-guided and conventional nasotracheal intubations using
videolaryngoscopy.
PMID- 29333713
TI - Difficult mask ventilation and muscle relaxation - a reply.
PMID- 29333714
TI - Mechanical ventilation mode and postoperative pulmonary complications.
PMID- 29333715
TI - Social prescribing and pre-operative care.
PMID- 29333716
TI - National standards for triaging elderly trauma patients.
PMID- 29333717
TI - Correction.
PMID- 29333718
TI - Standard abbreviations.
PMID- 29333719
TI - Ion Mobility-Enhanced Data-Independent Acquisitions Enable a Deep Proteomic
Landscape of Oligodendrocytes.
PMID- 29333720
TI - Degree of SGLT1 phosphorylation is associated with but does not determine segment
specific glucose transport features in the porcine small intestines.
AB - Glucose-induced electrogenic ion transport is higher in the porcine ileum
compared with the jejunum despite equal apical abundance of SGLT1. The objective
of this study was a detailed determination of SGLT1 and GLUT2 expressions at mRNA
and protein levels along the porcine small intestinal axis. Phosphorylation of
SGLT1 at serine 418 was assessed as a potential modulator of activity. Porcine
intestinal tissues taken along the intestinal axis 1 h or 3 h after feeding were
analyzed for relative mRNA (RT-PCR) and protein levels (immunoblot) of SGLT1,
pSGLT1, GLUT2, (p)AMPK, beta2 -receptor, and PKA substrates. Functional studies
on electrogenic glucose transport were done (Ussing chambers: short circuit
currents (Isc )). Additionally, effects of epinephrine (Epi) administration on
segment-specific glucose transport and pSGLT1 content were examined. SGLT1 and
GLUT2 expression was similar throughout the small intestines but lower in the
duodenum and distal ileum. pSGLT1 abundance was significantly lower in the ileum
compared with the jejunum associated with significantly higher glucose-induced
Isc . SGLT1 phosphorylation was not inducible by Epi. Epi treatment decreased
glucose-induced Isc and glucose flux rates in the jejunum but increased basal Isc
in the ileum. Epi-induced PKA activation was detectable in jejunal tissue. These
results may indicate that SGLT1 phosphorylation at Ser418 represents a structural
change to compensate for certain conditions that may decrease glucose transport
(unfavorable driving forces/changed apical membrane potential) rather than being
the cause for the overall differences in glucose transport characteristics
between the jejunum and ileum.
PMID- 29333721
TI - Carbohydrate dose influences liver and muscle glycogen oxidation and performance
during prolonged exercise.
AB - This study investigated the effect of carbohydrate (CHO) dose and composition on
fuel selection during exercise, specifically exogenous and endogenous (liver and
muscle) CHO oxidation. Ten trained males cycled in a double-blind randomized
order on 5 occasions at 77% VO2max for 2 h, followed by a 30-min time-trial (TT)
while ingesting either 60 g.h-1 (LG) or 75 g.h-113 C-glucose (HG), 90 g.h-1 (LGF)
or 112.5 g.h-113 C-glucose-13 C-fructose ([2:1] HGF) or placebo. CHO doses met or
exceed reported intestinal transporter saturation for glucose and fructose.
Indirect calorimetry and stable mass isotope [13 C] tracer techniques were
utilized to determine fuel use. TT performance was 93% "likely/probable" to be
improved with LGF compared with the other CHO doses. Exogenous CHO oxidation was
higher for LGF and HGF compared with LG and HG (ES > 1.34, P < 0.01), with the
relative contribution of LGF (24.5 +/- 5.3%) moderately higher than HGF (20.6 +/-
6.2%, ES = 0.68). Increasing CHO dose beyond intestinal saturation increased
absolute (29.2 +/- 28.6 g.h-1 , ES = 1.28, P = 0.06) and relative muscle glycogen
utilization (9.2 +/- 6.9%, ES = 1.68, P = 0.014) for glucose-fructose ingestion.
Absolute muscle glycogen oxidation between LG and HG was not significantly
different, but was moderately higher for HG (ES = 0.60). Liver glycogen oxidation
was not significantly different between conditions, but absolute and relative
contributions were moderately attenuated for LGF (19.3 +/- 9.4 g.h-1 , 6.8 +/-
3.1%) compared with HGF (30.5 +/- 17.7 g.h-1 , 10.1 +/- 4.0%, ES = 0.79 & 0.98).
Total fat oxidation was suppressed in HGF compared with all other CHO conditions
(ES > 0.90, P = 0.024-0.17). In conclusion, there was no linear dose response for
CHO ingestion, with 90 g.h-1 of glucose-fructose being optimal in terms of TT
performance and fuel selection.
PMID- 29333722
TI - Cardiovascular adjustments during anticipated postural changes.
AB - It is well-documented that feedforward cardiovascular responses occur at the
onset of exercise, but it is unclear if such responses are associated with other
types of movements. In this study, we tested the hypothesis that feedforward
cardiovascular responses occur when a passive (imposed) 60 degrees head-up tilt
is anticipated, such that changes in heart rate and carotid artery blood flow
(CBF) commence prior to the onset of the rotation. A light cue preceded head-up
tilts by 10 sec, and heart rate and CBF were determined for 5-sec time periods
prior to and during tilts. Even after these stimuli were provided for thousands
of trials spanning several months, no systematic changes in CBF and heart rate
occurred prior to tilts, and variability in cardiovascular adjustments during
tilt remained substantial over time. We also hypothesized that substitution of 20
degrees for 60 degrees tilts in a subset of trials would result in exaggerated
cardiovascular responses (as animals expected 60 degrees tilts), which were not
observed. These data suggest that cardiovascular adjustments during passive
changes in posture are mainly elicited by feedback mechanisms, and that
anticipation of passive head-up tilts does not diminish the likelihood that a
decrease in carotid blood flow will occur during the movements.
PMID- 29333723
TI - Nandrolone-induced nuclear accumulation of MyoD protein is mediated by Numb, a
Notch inhibitor, in C2C12 myoblasts.
AB - Signaling via the androgen receptor (AR) stimulates myogenic progenitor
differentiation. In addition, myogenic differentiation factor D (MyoD) and Numb,
a Notch inhibitor, play key roles in regulating myogenic differentiation.
Nandrolone, an anabolic steroid, upregulates both MyoD and Numb expression in
myogenic cells. However, the molecular mechanisms by which MyoD is upregulated by
nandrolone are unclear. Moreover, the potential crosstalk between nandrolone,
MyoD, and Numb is not well understood. With these considerations in mind, we
examined the effects of nandrolone on the expression of MyoD mRNA and protein,
and determined the interactions of MyoD and Numb in the presence or absence of
nandrolone in differentiating C2C12 myoblasts. Nandrolone increased MyoD mRNA and
protein expression and significantly enhanced nuclear translocation of MyoD
protein. The later effect of nandrolone was blunted by siRNA against Numb.
Immunoprecipitation (IP) studies confirmed that Numb forms complexes with MyoD.
Chromatin IP revealed that in the presence of nandrolone, Numb is recruited to a
region of the MyH7 promotor containing the E-box to which MyoD binds. These data
indicate that nandrolone-regulated MyoD activation occurs mainly through a
posttranslational mechanism which promotes MyoD nuclear accumulation, and suggest
that this effect of nandrolone is, at least in part, mediated by Numb.
PMID- 29333724
TI - Voluntary activation and twitch potentiation of the elbow flexors across
supinated, neutral, and pronated forearm orientations.
AB - Elbow flexion force depends on forearm orientation with supinated and neutral
being stronger than pronated. The purpose of this study was to assess the
influence of forearm orientation on voluntary activation (VA), postactivation
potentiation (PAP), and twitch properties. Eleven males (23 +/- 3 years)
performed isometric elbow flexion maximal voluntary contractions (MVC) in
supinated, neutral, and pronated forearm orientations with supramaximal
stimulation to the biceps brachii muscle belly before, during, and after the MVC.
MVC and VA were higher in supinated (213.6 +/- 49.6 N; 93.0 +/- 5.2%) and neutral
(243.6 +/- 48.0 N; 96.1 +/- 3.2%) compared with pronated (113.6 +/- 21.3 N; 70.9
+/- 20.4%) (P < 0.05), while PAP did not differ across the three orientations
(71.6 +/- 42.2%) (P > 0.05). In the rested state, pronated peak tension (PT) was
less compared with supinated (42%). In the potentiated state, pronated PT was
less than supinated (50%) and neutral (53%) (P < 0.05). Reduced strength in the
pronated orientation is partially attributed to reduced drive; however,
reductions in peak tension indicate that there also is a mechanical disadvantage
when the forearm is placed into a pronated orientation, and this does not alter
PAP.
PMID- 29333725
TI - Chemoreflex function and brain blood flow during upright posture in men and
women.
AB - Orthostatic intolerance is more common in women than men, and some studies have
found that women in the early follicular (EF) phase of the menstrual cycle
experience the greatest feelings of lightheadedness. Chemoreflex function while
supine or upright was investigated to determine the potential contribution of
ventilatory control to these phenomena. Men (n = 13) and women (n = 14) were
tested while supine and 70 degrees upright (head-up tilt [HUT]) and given: (1)
normoxia or (2) hypercapnia (5% CO2 ). Women were tested during the EF phase
(days 2-5) and the midluteal phase (ML; days 18-24). During HUT, all groups
reduced cerebrovascular resistance index (men: 1.45 +/- 0.08 to 1.42 +/- 0.07
mmHg/(cm.sec), EF: 1.38 +/- 0.11 to 1.26 +/- 0.10 mmHg/(cm.sec), ML: 1.25 +/-
0.07 to 1.09 +/- 0.07 mmHg/(cm.sec); P <= 0.019); however, only men increased
ventilation (men: 11.99 +/- 0.65 to 13.24 +/- 0.83 L/min; P < 0.01). In response
to hypercapnia in the supine position, men had a smaller increase of diastolic
middle cerebral artery velocity compared to women in the ML phase (men: +9.1 +/-
2.0 cm/sec, ML: +15.7 +/- 3.1 cm/sec, P = 0.039). During hypercapnia in HUT
(compared to hypercapnia while supine), all groups had an augmented increase of
ventilation (men: +7.46 +/- 1.34 vs. +5.84 +/- 1.09 L/min, EF: +6.71 +/- 0.83 vs.
+5.48 +/- 0.66 L/min, ML: +7.99 +/- 1.13 vs. +5.65 +/- 0.81 L/min; P <= 0.028),
suggesting that all groups experienced augmentation of the CO2 chemoreflex;
however, only men had an augmented increase of mean arterial pressure (+0.10 +/-
0.58 to +4.71 +/- 0.87 mmHg; P <= 0.017). Our results indicate that men have
different ventilatory responses to upright tilt compared to women, and that the
CO2 chemoreflex response is enhanced in upright posture in both sexes.
Furthermore, sexually dimorphic blood pressure responses to this chemoreflex
enhancement are evident.
PMID- 29333726
TI - Calcium current properties in dystrophin-deficient ventricular cardiomyocytes
from aged mdx mice.
AB - Duchenne muscular dystrophy (DMD), caused by mutations in the gene encoding for
the cytoskeletal protein dystrophin, is linked with severe cardiac complications
including cardiomyopathy development and cardiac arrhythmias. We and others
recently reported that currents through L-type calcium (Ca) channels were
significantly increased, and channel inactivation was reduced in dystrophin
deficient ventricular cardiomyocytes derived from the mdx mouse, the most
commonly used animal model for human DMD. These gain-of-function Ca channel
abnormalities may enhance the risk of Ca-dependent arrhythmias and cellular Ca
overload in the dystrophic heart. All studies, which have so far investigated L
type Ca channel properties in dystrophic cardiomyocytes, have used hearts from
either neonatal or young adult mdx mice as cell source. In consequence, the
dimension of the Ca channel abnormalities present in the severely-diseased aged
dystrophic heart has remained unknown. Here, we have studied potential
abnormalities in Ca currents and intracellular Ca transients in ventricular
cardiomyocytes derived from aged dystrophic mdx mice. We found that both the L
type and T-type Ca current properties of mdx cardiomyocytes were similar to those
of myocytes derived from aged wild-type mice. Accordingly, Ca release from the
sarcoplasmic reticulum was normal in cardiomyocytes from aged mdx mice. This
suggests that, irrespective of the presence of a pronounced cardiomyopathy in
aged mdx mice, Ca currents and Ca release in dystrophic cardiomyocytes are
normal. Finally, our data imply that dystrophin- regulation of L-type Ca channel
function in the heart is lost during aging.
PMID- 29333727
TI - The relation between maximal voluntary force in m. palmaris longus and the
temporal and spatial summation of muscle fiber recruitment in human subjects.
AB - This study aimed at looking at the frequency (T-score) and the amplitude (S
score) of fiber use during contraction of a forearm muscle, m. palmaris longus,
as measured by acoustic myography (AMG). An additional aim was to relate the T-
and S-scores to the recorded force obtained from a hand dynamometer. The
hypothesis being that temporal and spatial summation of muscle fiber contraction
in a given muscle during a given movement, can together describe a given obtained
force. Force measurements were carried out on 12 healthy human subjects aged 19
68 years (6 men & 6 women), while their m. palmaris longus contractile function
was measured using an acoustic myography CURO device. Force production was varied
from 90 to 10% of assessed maximal voluntary force (MVF), and also monitored over
a 1 min period of 50% MVF. Linear regression analysis was applied to relate force
to spatial and temporal summation. Muscle strength was sustained by changing the
frequency and/or the number of active fibere at any given point in time. Force
production, whilst stronger for men than women, was regulated in a similar
fashion for both sexes and was closely correlated with the AMG T- and S-scores.
It is concluded that AMG is a noninvasive method which can be readily applied to
accurately describe how a subject uses a given muscle during any given movement.
These findings have relevance when considering training strategies in subjects
with muscle trauma or disease, in the elderly, or for both amateur and top
professional athletes.
PMID- 29333728
TI - Population correlations do not support the existence of set points for blood
levels of calcium or glucose - a new model for homeostasis.
AB - The prevailing teaching regarding homeostasis, and in particular endocrine
homeostasis, includes the fundamental concept of a "set point," which represents
a target or optimum level defended by physiological control mechanisms. Analogies
for the description and teaching of this concept have included thermostats and
cruise controls. We previously demonstrated that such a set-point model of
regulation implies that in population data of parameter set point/controlling
hormone levels, correlations between the parameter and its controlling hormone
must be in the direction of the response of the parameter to its controlling
hormone, and that in thyroid homeostasis this relationship is not observed. In
this work we similarly examined population correlations, extracted from the
literature, for the parameters glucose and calcium, and their controlling
hormones. We found 10 correlations. Most were highly significant (P < 0.01). All
were in the direction of the response of the controlling hormone to the
parameter. Therefore, none were consistent with the pattern implied by a set
point model of regulation. Instead all were consistent with an "equilibrium
point" model of regulation, whereby ambient levels have no particular connotation
to the individual, and result passively from the interplay of physiological
processes. We conclude that glucose and calcium regulation, like thyroid
regulation, are not centered on set points. This may reflect a general property
of homeostasis. We provide an alternative mechanistic analogy, without a set
point, for the heuristic description and teaching, of homeostasis.
PMID- 29333729
TI - Immunoengineering with biomaterials for enhanced cancer immunotherapy.
AB - Cancer immunotherapy has recently shown dramatic clinical success inducing
durable response in patients of a wide variety of malignancies. Further
improvement of the clinical outcome with immune related cancer treatment requests
more exquisite manipulation of a patient's immune system with increased immunity
against diseases while mitigating the toxicities. To meet this challenge,
biomaterials applied to immunoengineering are being developed to achieve tissue-
and/or cell-specific immunomodulation and thus could potentially enhance both the
efficacy and safety of current cancer immunotherapies. Here, we review the recent
advancement in the field of immunoengineering using biomaterials and their
applications in promoting different modalities of cancer immunotherapies, with
focus on cell-, antibody-, immunomodulator-, and gene-based immune related
treatments and their combinations with conventional therapies. Challenges and
opportunities are discussed in applying biomaterials engineering strategies in
the development of future cancer immunotherapies. This article is categorized
under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic
Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies
Implantable Materials and Surgical Technologies > Nanomaterials and Implants.
PMID- 29333730
TI - Day-to-day mastery and self-efficacy changes during a smoking quit attempt: Two
studies.
AB - OBJECTIVE: In social-cognitive theory, it is hypothesized that mastery
experiences (successfully implementing behaviour change) are a source of self
efficacy, and self-efficacy increases the opportunity for experiencing mastery.
Vicarious experiences (seeing others succeed) are suggested as another source of
self-efficacy. However, the hypothesis of this reciprocal relationship has not
been tested using a day-to-day design. DESIGN: This article reports findings from
two intensive longitudinal studies, testing the reciprocal relationship of self
efficacy and its two main sources within the naturally occurring process of
quitting smoking (without intervention). Smokers (Study 1: N = 100 smokers in
smoker-non-smoker couples (1,787 observations); Study 2; N = 81 female (1,401
observations) and N = 79 male smokers (1,328 observations) in dual-smoker
couples) reported their mastery experiences (not smoking the entire day; in Study
2, mastery experience of partner served as vicarious experience) and smoking
specific self-efficacy for 21 days after a self-set quit date. METHODS: Time
lagged multilevel analyses were conducted using change-predicting-change models.
RESULTS: Increases in mastery experiences predicted changes in self-efficacy, and
increases in self-efficacy predicted changes in mastery experiences in Study 1.
Study 2 replicated these results and showed contagion effects (partners' mastery
on individuals' mastery and partners' self-efficacy on individuals' self
efficacy), but found no evidence for a link between vicarious experiences
(partners' mastery experiences) and individuals' self-efficacy. CONCLUSIONS: This
article demonstrates that mastery experiences and self-efficacy show a reciprocal
relationship within smokers during a quit attempt in a day-to-day design, as well
as contagion effects in couples when both partners try to quit simultaneously.
Statement of Contribution What is already known on this subject? Self-efficacy is
one of the strongest correlates of quitting smoking. Despite the assumptions on
how self-efficacy is built formulated by Bandura two decades ago, there is only
little empirical evidence on the origins of self-efficacy. The open research
questions for these two studies were whether mastery experiences (experiencing
success with the new behavior) and vicarious experiences (seeing others succeed)
facilitate the smoking cessation process, whether mastery experiences and self
efficacy affect one another reciprocally and whether intimate partners serve as
role models for each other. What does this study add? Mastery experiences and
self-efficacy are mutually depended on a day-to-day basis within the smoking
cessation process. Effects of mastery experiences fade rapidly, indicating that
constant successes are needed to keep up self-efficacy. Dual-smoker couples show
similar changes in a contagious way - if mastery experiences increase in one
person, mastery experiences increase in the partner; if self-efficacy increases
in one person, self-efficacy increases in the partner, too. No support for
vicarious experiences (mastery experiences in one person affecting self-efficacy
in the partner and vice versa) as sources of self-efficacy in the quitting
process was found.
PMID- 29333731
TI - William G. Bradley, Jr, MD, PhD, FACR (1942-2017).
PMID- 29333732
TI - Artificial intelligence will reduce the need for clinical medical physicists.
PMID- 29333733
TI - State of the JACMP.
PMID- 29333734
TI - Synthesis, Cytotoxic, and Antibacterial Evaluation of Quinazolinone Derivatives
with Substituted Amino Moiety.
AB - A series of novel quinazolinone derivatives containing a substituted amino moiety
were synthesized, evaluated for their cytotoxic and antibacterial activities. The
results of MTT assay showed that all synthesized target compounds 5A - 5O showed
potent cytotoxicity against SGC-7901 (IC50 , 0.72 - 1.41 MUm). Moreover, the
compounds 5D, 5I, and 5K showed better selectivity as compared with positive
controls pemetrexed and MTX due to weak cytotoxicity against normal tissue cell
line HUVSMC. Among synthesized compounds, the compounds 5E, 5J, 5L, and 5N showed
broad-spectrum cytotoxic activities against at least four cancer cell lines at a
micromolar level. The results of antibacteria evaluation revealed that all
synthesized compounds showed good to moderate antibacterial activities against
Gram-negative bacteria Escherichia coli. Among them, the MIC values of the
compounds 5C, 5F, and 5M were 0.31 MUg/mL.
PMID- 29333735
TI - Hot-Electron-Assisted Femtosecond All-Optical Modulation in Plasmonics.
AB - The optical Kerr nonlinearity of plasmonic metals provides enticing prospects for
developing reconfigurable and ultracompact all-optical modulators. In
nanostructured metals, the coherent coupling of light energy to plasmon
resonances creates a nonequilibrium electron distribution at an elevated electron
temperature that gives rise to significant Kerr optical nonlinearities. Although
enhanced nonlinear responses of metals facilitate the realization of efficient
modulation devices, the intrinsically slow relaxation dynamics of the
photoexcited carriers, primarily governed by electron-phonon interactions,
impedes ultrafast all-optical modulation. Here, femtosecond (~190 fs) all-optical
modulation in plasmonic systems via the activation of relaxation pathways for hot
electrons at the interface of metals and electron acceptor materials, following
an on-resonance excitation of subradiant lattice plasmon modes, is demonstrated.
Both the relaxation kinetics and the optical nonlinearity can be actively tuned
by leveraging the spectral response of the plasmonic design in the linear regime.
The findings offer an opportunity to exploit hot-electron-induced nonlinearities
for design of self-contained, ultrafast, and low-power all-optical modulators
based on plasmonic platforms.
PMID- 29333736
TI - Underestimated caregiver burden by cancer patients and its association with
quality of life, depression and anxiety among caregivers.
AB - This study examined how patients with cancer estimate caregiver burden (CB) and
the association between their underestimation of CB and their caregivers' self
ratings of their quality of life (CQOLC-K; Korean version of the Caregiver
Quality of Life Index-Cancer), depression and anxiety (Korean version of the
Hospital Anxiety and Depression Scale). Participants consisted of 990 patient
caregiver dyads recruited from a nationwide cross-sectional survey conducted in
South Korea. Medical baseline data were retrieved from the hospital information
systems of the participating centres. The patients with cancer who underestimated
CB ranged from 18.62% (for physical CB) to 23.33% (for social CB). They had less
advanced cancer, a lower income, were the caregiver's spouse, reported higher
levels of family avoidance of communication about cancer, and had female
caregivers. The patients' underestimation of CB was significantly related to
lower CQoL and higher levels of caregiver depression and anxiety. The current
study provides empirical evidence for the link between the underestimation of CB
by patients with cancer and compromised caregiving experiences of cancer
caregivers. Open family communication about cancer was discussed as one of
several practical strategies for decreasing patients' underestimation of CB.
PMID- 29333737
TI - Recent advances in veterinary radiation oncology.
PMID- 29333738
TI - Antibacterial and Antifungal Activity of Poly(Lactic Acid)-Bovine Lactoferrin
Nanofiber Membranes.
AB - Antimicrobial materials have become relevant for local therapies preventing
microbial resistance induced by systemic antibiotic treatments. This work reports
the development of electrospun poly(lactic acid) (PLLA) nanofiber membranes
loaded with bovine lactoferrin (bLF) up to 20 wt%. The membranes present smooth
and nondefective fibers with mean diameters between 717 +/- 197 and 495 +/- 127
nm, and an overall porosity of ~80%. The hydrophobicity of the PLLA membranes is
reduced by the presence of bLF. The release profile of bLF correlates with an
anomalous transport model, with 17.7 +/- 3.6% being released over 7 weeks. The
nanofiber mats show no cytotoxicity on human skin fibroblasts and even promote
cell proliferation after short exposure periods. Furthermore, the developed
membranes display antifungal activity against Aspergillus nidulans by inhibiting
spore germination and mycelial growth. These results evidence the strong
potential of bLF-PLLA nanofiber membranes to be used as antifungal dressings.
PMID- 29333739
TI - Nickel-Based (Photo)Electrocatalysts for Hydrogen Production.
AB - Hydrogen is considered a promising energy carrier for replacing traditional
fossil fuels. Electrochemical or solar-driven water splitting is a green and
sustainable method of producing hydrogen. To lower the overpotential and minimize
energy costs, numerous reports have focused on developing noble-metal-free
catalysts for hydrogen production, with special attention paid to nickel-based
materials. Herein, the current state of research on the use of Ni-based materials
as electrocatalysts, cocatalysts, and photoactive materials in hydrogen
production is reviewed. Recent research efforts toward the development of various
Ni-based (photo)electrocatalysts, their applications in hydrogen production, and
the corresponding mechanisms are covered. The approaches used to improve or
optimize these materials are summarized, and the key remaining challenges are
discussed.
PMID- 29333740
TI - Pharmacokinetics, disposition, and plasma concentrations of dimethyl sulfoxide
(DMSO) in the horse following topical, oral, and intravenous administration.
AB - Compartmental models were used to investigate the pharmacokinetics of intravenous
(i.v.), oral (p.o.), and topical (TOP) administration of dimethyl sulfoxide
(DMSO). The plasma concentration-time curve following a 15-min i.v. infusion of
DMSO was described by a two-compartment model. Median and range of alpha
(t1/2alpha ) and beta (t1/2beta ) half-lives were 0.029 (0.026-0.093) and 14.1
(6.6-16.4) hr, respectively. Plasma concentration-time curves of DMSO following
p.o. and TOP administration were best described by one-compartment absorption and
elimination models. Following the p.o. administration, median absorption (t1/2ab
) and elimination (t1/2e ) half-lives were 0.15 (0.01-0.77) and 15.5 (8.5-25.2)
hr, respectively. The plasma concentrations of DMSO were 47.4-129.9 MUg/ml,
occurring between 15 min and 4 hr. The fractional absorption (F) during a 24-hr
period was 47.4 (22.7-98.1)%. Following TOP administrations, the median t1/2ab
and t1/2e were 1.2 (0.49-2.3) and 4.5 (2.1-11.0) hr, respectively. Plasma
concentrations were 1.2-8.2 MUg/ml occurring at 2-4 hr. Fractional absorption
following TOP administration was 0.48 (0.315-4.4)% of the dose administered.
Clearance (Cl) of DMSO following the i.v. administration was 3.2 (2.2-6.7) ml hr
1 kg-1 . The corrected clearances (ClF ) for p.o. and TOP administrations were
2.9 (1.1-5.5) and 4.5 (0.52-18.2) ml hr-1 kg-1 .
PMID- 29333741
TI - P-Type Low-Molecular-Weight Hydrogelators.
AB - As the use of low-molecular-weight gelators (LMWGs) as components in single and
multicomponent systems for optoelectronic and solar cell applications increases,
so does the need for more functional gelators. There are relatively few examples
of p-type gelators that can be used in such systems. Here, the synthesis and
characterization of three amino-acid-functionalized p-type gelators based on
terthiophene, tetrathiafulvalene, and oligo(phenylenevinylene) are described. The
cores of these molecules are already used as electron donors in optoelectronic
applications. These newly designed molecules can gel water to form highly
organized structures, which can be dried into thin films that show p-type
behavior.
PMID- 29333743
TI - Dyadic coping and marital adjustment during pregnancy: A cross-sectional study of
Italian couples expecting their first child.
AB - Although the transition to parenthood is currently defined as a normative event,
it can be potentially stressful for the couple relationship as it may contribute
to psychological distress and reduced marital satisfaction. Using the systemic
transactional conceptualisation of stress and coping as a theoretical framework,
we claimed that the ability of the parents-to-be to adjust to their new roles and
identity is influenced by dyadic coping strategies. This study examined the
effects of dyadic coping on marital adjustment in a sample of 78 primiparous
couples. Women and partners completed the Dyadic Adjustment Scale and the Dyadic
Coping Questionnaire during late pregnancy. Data were analysed using the Actor
Partner Interdependence Model. Results revealed that both women and partners'
scores on positive dyadic coping behaviours contributed to higher marital
adjustment, suggesting that risks for marital dissatisfaction may exist for
couples not able to implement adaptive dyadic coping strategies, or for those
unsatisfied with the implemented coping behaviours.
PMID- 29333744
TI - High-Performance Organic Bulk-Heterojunction Solar Cells Based on Multiple-Donor
or Multiple-Acceptor Components.
AB - Organic solar cells (OSCs) based on bulk heterojunction structures are promising
candidates for next-generation solar cells. However, the narrow absorption
bandwidth of organic semiconductors is a critical issue resulting in insufficient
usage of the energy from the solar spectrum, and as a result, it hinders
performance. Devices based on multiple-donor or multiple-acceptor components with
complementary absorption spectra provide a solution to address this issue. OSCs
based on multiple-donor or multiple-acceptor systems have achieved power
conversion efficiencies over 12%. Moreover, the introduction of an additional
component can further facilitate charge transfer and reduce charge recombination
through cascade energy structure and optimized morphology. This progress report
provides an overview of the recent progress in OSCs based on multiple-donor
(polymer/polymer, polymer/dye, and polymer/small molecule) or multiple-acceptor
(fullerene/fullerene, fullerene/nonfullerene, and nonfullerene/nonfullerene)
components.
PMID- 29333742
TI - Parvalbumin fast-spiking interneurons are selectively altered by paediatric
traumatic brain injury.
AB - KEY POINTS: Traumatic brain injury (TBI) in children remains a leading cause of
death and disability and it remains poorly understood why children have worse
outcomes and longer recover times. TBI has shown to alter cortical excitability
and inhibitory drive onto excitatory neurons, yet few studies have directly
examined changes to cortical interneurons. This is addressed in the present study
using a clinically relevant model of severe TBI (controlled cortical impact) in
interneuron cell type specific Cre-dependent mice. Mice subjected to controlled
cortical impact exhibit specific loss of parvalbumin (PV) but not somatostatin
immunoreactivity and cell density in the peri-injury zone. PV interneurons are
primarily of a fast-spiking (FS) phenotype that persisted in the peri-injury zone
but received less frequent inhibitory and stronger excitatory post-synaptic
currents. The targeted loss of PV-FS interneurons appears to be distinct from
previous reports in adult mice suggesting that TBI-induced pathophysiology is
dependent on the age at time of impact. ABSTRACT: Paediatric traumatic brain
injury (TBI) is a leading cause of death and disability in children.
Traditionally, ongoing neurodevelopment and neuroplasticity have been considered
to confer children with an advantage following TBI. However, recent findings
indicate that the paediatric brain may be more sensitive to brain injury.
Inhibitory interneurons are essential for proper cortical function and are
implicated in the pathophysiology of TBI, yet few studies have directly
investigated TBI-induced changes to interneurons themselves. Accordingly, in the
present study, we examine how inhibitory neurons are altered following controlled
cortical impact (CCI) in juvenile mice with targeted Cre-dependent fluorescence
labelling of interneurons (Vgat:Cre/Ai9 and PV:Cre/Ai6). Although CCI failed to
alter the number of excitatory neurons or somatostatin-expressing interneurons in
the peri-injury zone, it significantly decreased the density of parvalbumin (PV)
immunoreactive cells by 71%. However, PV:Cre/Ai6 mice subjected to CCI showed a
lower extent of fluorescence labelled cell loss. PV interneurons are
predominantly of a fast-spiking (FS) phenotype and, when recorded
electrophysiologically from the peri-injury zone, exhibited intrinsic properties
similar to those of control neurons. Synaptically, CCI induced a decrease in
inhibitory drive onto FS interneurons combined with an increase in the strength
of excitatory events. The results of the present study indicate that CCI induced
both a loss of PV interneurons and an even greater loss of PV expression. This
suggests caution is required when interpreting changes in PV immunoreactivity
alone as direct evidence of interneuronal loss. Furthermore, in contrast to
reports in adults, TBI in the paediatric brain selectively alters PV-FS
interneurons, primarily resulting in a loss of interneuronal inhibition.
PMID- 29333745
TI - Increased sensitivity and high specificity of indirect immunofluorescence in
detecting IgG subclasses for diagnosis of bullous pemphigoid.
AB - BACKGROUND: Indirect immunofluorescence (IIF) microscopy on monkey oesophagus is
an important assay for the diagnosis of bullous pemphigoid (BP). Its relatively
low sensitivity (60-80%) may be partly due to insufficient detection of minor IgG
subclasses. AIM: To determine the operating characteristics of an IgG subclass in
IIF. METHODS: We designed a retrospective, dual-centre, controlled cohort study
on sera from 64 BP sera that had been rated as false negatives by traditional IIF
microscopy, and assessed circulating IgG1 , IgG3 and IgG4 autoantibodies.
RESULTS: The sensitivities of IIF in detecting IgG1 , IgG3 , IgG4 and all three
in combination were 45.3%, 18.8%, 32.8% and 48.4%, respectively. Specificities
were > 97%. CONCLUSION: Detection of IgG subclass (especially IgG1 and IgG4 )
autoantibodies by IIF on monkey oesophagus can significantly improve diagnostic
performance of IIF microscopy for diagnosis of BP.
PMID- 29333746
TI - Novel KIT variants for dominant white in the Australian horse population.
PMID- 29333747
TI - Rapid, Regioselective Living Ring-Opening Metathesis Polymerization of Bio
Derivable Asymmetric Tricyclic Oxanorbornenes.
AB - The synthesis of a range of alkyl esters (methyl, n-butyl, and n-decyl) prepared
via Steglich esterification of the thermodynamically controlled exo, exo Diels
Alder adduct of furfuryl alcohol and maleic anhydride is reported. Subsequent
ring-opening metathesis polymerization of these bio-derivable tricyclic
oxanorbornene analogs delivers polymers with targeted molar mass and low molar
mass dispersity. The polymerizations are rapid with complete monomer conversion
achieved within 15 min. Significantly, the presence of the cyclic lactone at the
bridgehead of these monomers leads to polymers with high regioregularity (>85%
head-to-tail) and high stereoregularity (>75% trans). The resultant polymers
display both high thermal stability and high glass transition temperatures. This
new class of oxanorbornene monomer, accessed from bio-derivable furfuryl alcohol
and maleic anhydride, may be further tailored to incorporate a range of
functional moieties. Furthermore, the exceptional properties of the derived
polymers indicate potential in a range of applications.
PMID- 29333748
TI - Near-Infrared Light-Sensitive Polyvinyl Alcohol Hydrogel Photoresist for
Spatiotemporal Control of Cell-Instructive 3D Microenvironments.
AB - Advanced hydrogel systems that allow precise control of cells and their 3D
microenvironments are needed in tissue engineering, disease modeling, and drug
screening. Multiphoton lithography (MPL) allows true 3D microfabrication of
complex objects, but its biological application requires a cell-compatible
hydrogel resist that is sufficiently photosensitive, cell-degradable, and
permissive to support 3D cell growth. Here, an extremely photosensitive cell
responsive hydrogel composed of peptide-crosslinked polyvinyl alcohol (PVA) is
designed to expand the biological applications of MPL. PVA hydrogels are formed
rapidly by ultraviolet light within 1 min in the presence of cells, providing
fully synthetic matrices that are instructive for cell-matrix remodeling,
multicellular morphogenesis, and protease-mediated cell invasion. By focusing a
multiphoton laser into a cell-laden PVA hydrogel, cell-instructive extracellular
cues are site-specifically attached to the PVA matrix. Cell invasion is thus
precisely guided in 3D with micrometer-scale spatial resolution. This robust
hydrogel enables, for the first time, ultrafast MPL of cell-responsive synthetic
matrices at writing speeds up to 50 mm s-1 . This approach should enable facile
photochemical construction and manipulation of 3D cellular microenvironments with
unprecedented flexibility and precision.
PMID- 29333750
TI - Hydroperoxide Traces in Common Cyclic Ethers as Initiators for Controlled RAFT
Polymerizations.
AB - Herein, a reversible addition-fragmentation chain transfer (RAFT) polymerization
is introduced for reactive monomers like N-acryloylpyrrolidine or N,N
dimethylacrylamide working without a conventional radical initiator. As a very
straightforward proof of principle, the method takes advantage of the usually
inconvenient radical-generating hydroperoxide contaminations in cyclic ethers
like tetrahydrofuran or 1,4-dioxane, which are very common solvents in polymer
sciences. The polymerizations are surprisingly well controlled and the polymers
can be extended with a second block, indicating their high livingness. "Solvent
initiated" RAFT polymerizations hence prove to be a feasible access to tailored
materials with minimal experimental effort and standard laboratory equipment,
only requiring the following ingredients: hydroperoxide-contaminated solvent,
monomer, and RAFT agent. In other respects, however, the potential coinitiating
ability of the used solvent is to be considered when investigating the kinetics
of RAFT polymerizations or aiming for the synthesis of high-livingness polymers,
e.g., multiblock copolymers.
PMID- 29333749
TI - Tetralogy of Fallot with left ventricular clot.
PMID- 29333751
TI - Identification of the Minimal Glycotope of Streptococcus pneumoniae 7F Capsular
Polysaccharide using Synthetic Oligosaccharides.
AB - Streptococcus pneumoniae causes life-threatening diseases including meningitis,
pneumonia and sepsis. Existing glycoconjugate vaccines based on purified capsular
polysaccharides are widely used and help to prevent millions of deaths every
year. Herein, the total syntheses of oligosaccharides resembling portions of the
S. pneumoniae serotype 7F (ST7F) capsular polysaccharide repeating unit are
reported. To define minimal glycan epitopes, glycan microarrays containing the
synthetic oligosaccharides were used to screen human reference serum and revealed
that both side chains of the ST7F play a key role in antigen recognition. The
identification of protective minimal epitopes is vital to design efficient semi-
and fully-synthetic glycoconjugate vaccines.
PMID- 29333752
TI - Workplace design for the Australian residential aged care workforce.
AB - OBJECTIVES: This research explored residential aged care (RAC) workplace design
features that influence how RAC staff feel valued, productive, safe, like they
belong and connected. A secondary aim was to validate emerging themes about RAC
design features with stakeholders. METHODS: A multistage qualitative study was
conducted in one RAC facility with 100 residents in outer metropolitan Melbourne:
(i) photo-elicitation - photographs were used to prompt discussions with RAC
staff; (ii) individual interviews with RAC directors; and (iii) validity testing
with the advisory committee occurred. RESULTS: Key workplace design features that
influenced how RAC staff feel valued, productive, safe, like they belong and
connected included the following: (i) home-like environment; (ii) access to
outdoor spaces; (iii) quality indoor environment; and (iv) access to safe, open
and comfortable workplaces. CONCLUSIONS: Key workplace design features that
matter to RAC staff in a 'shared workspace' exist. Increasing demands upon RAC
requires evidence-based workplace design policy and evaluation approaches that
support RAC staff to work in RAC shared workspaces.
PMID- 29333753
TI - Comparative performance of different scale-down simulators of substrate gradients
in Penicillium chrysogenum cultures: the need of a biological systems response
analysis.
AB - In a 54 m3 large-scale penicillin fermentor, the cells experience substrate
gradient cycles at the timescales of global mixing time about 20-40 s. Here, we
used an intermittent feeding regime (IFR) and a two-compartment reactor (TCR) to
mimic these substrate gradients at laboratory-scale continuous cultures. The IFR
was applied to simulate substrate dynamics experienced by the cells at full scale
at timescales of tens of seconds to minutes (30 s, 3 min and 6 min), while the
TCR was designed to simulate substrate gradients at an applied mean residence
time (tauc) of 6 min. A biological systems analysis of the response of an
industrial high-yielding P. chrysogenum strain has been performed in these
continuous cultures. Compared to an undisturbed continuous feeding regime in a
single reactor, the penicillin productivity (qPenG ) was reduced in all scale
down simulators. The dynamic metabolomics data indicated that in the IFRs, the
cells accumulated high levels of the central metabolites during the feast phase
to actively cope with external substrate deprivation during the famine phase. In
contrast, in the TCR system, the storage pool (e.g. mannitol and arabitol)
constituted a large contribution of carbon supply in the non-feed compartment.
Further, transcript analysis revealed that all scale-down simulators gave
different expression levels of the glucose/hexose transporter genes and the
penicillin gene clusters. The results showed that qPenG did not correlate well
with exposure to the substrate regimes (excess, limitation and starvation), but
there was a clear inverse relation between qPenG and the intracellular glucose
level.
PMID- 29333755
TI - Writing: be mindful of context.
PMID- 29333754
TI - A guide to analysis and reconstruction of serial block face scanning electron
microscopy data.
AB - Serial block face scanning electron microscopy (SBF-SEM) is a relatively new
technique that allows the acquisition of serially sectioned, imaged and digitally
aligned ultrastructural data. There is a wealth of information that can be
obtained from the resulting image stacks but this presents a new challenge for
researchers - how to computationally analyse and make best use of the large
datasets produced. One approach is to reconstruct structures and features of
interest in 3D. However, the software programmes can appear overwhelming, time
consuming and not intuitive for those new to image analysis. There are a limited
number of published articles that provide sufficient detail on how to do this
type of reconstruction. Therefore, the aim of this paper is to provide a detailed
step-by-step protocol, accompanied by tutorial videos, for several types of
analysis programmes that can be used on raw SBF-SEM data, although there are more
options available than can be covered here. To showcase the programmes, datasets
of skeletal muscle from foetal and adult guinea pigs are initially used with
procedures subsequently applied to guinea pig cardiac tissue and locust brain.
The tissue is processed using the heavy metal protocol developed specifically for
SBF-SEM. Trimmed resin blocks are placed into a Zeiss Sigma SEM incorporating the
Gatan 3View and the resulting image stacks are analysed in three different
programmes, Fiji, Amira and MIB, using a range of tools available for
segmentation. The results from the image analysis comparison show that the
analysis tools are often more suited to a particular type of structure. For
example, larger structures, such as nuclei and cells, can be segmented using
interpolation, which speeds up analysis; single contrast structures, such as the
nucleolus, can be segmented using the contrast-based thresholding tools. Knowing
the nature of the tissue and its specific structures (complexity, contrast, if
there are distinct membranes, size) will help to determine the best method for
reconstruction and thus maximize informative output from valuable tissue.
PMID- 29333756
TI - Medical students should know their limitations.
PMID- 29333757
TI - Optimising workplace-based assessment.
PMID- 29333758
TI - Benefit of team over individual near-peer teachers.
PMID- 29333759
TI - Responding to student preferences: a balancing act.
PMID- 29333760
TI - Supporting medical students with disabilities.
PMID- 29333761
TI - Simulated patients uncovered.
PMID- 29333762
TI - Pemphigus herpetiformis with autoantibodies to desmocollins 1, 2 and 3.
PMID- 29333763
TI - Polymer-Passivated Inorganic Cesium Lead Mixed-Halide Perovskites for Stable and
Efficient Solar Cells with High Open-Circuit Voltage over 1.3 V.
AB - Cesium-based trihalide perovskites have been demonstrated as promising light
absorbers for photovoltaic applications due to their superb composition
stability. However, the large energy losses (Eloss ) observed in inorganic
perovskite solar cells has become a major hindrance impairing the ultimate
efficiency. Here, an effective and reproducible method of modifying the interface
between a CsPbI2 Br absorber and polythiophene hole-acceptor to minimize the
Eloss is reported. It is demonstrated that polythiophene, deposited on the top of
CsPbI2 Br, can significantly reduce electron-hole recombination within the
perovskite, which is due to the electronic passivation of surface defect states.
In addition, the interfacial properties are improved by a simple annealing
process, leading to significantly reduced energy disorder in polythiophene and
enhanced hole-injection into the hole-acceptor. Consequently, one of the highest
power conversion efficiency (PCE) of 12.02% from a reverse scan in inorganic
mixed-halide perovskite solar cells is obtained. Modifying the perovskite films
with annealing polythiophene enables an open-circuit voltage (VOC ) of up to 1.32
V and Eloss of down to 0.5 eV, which both are the optimal values reported among
cesium-lead mixed-halide perovskite solar cells to date. This method provides a
new route to further improve the efficiency of perovskite solar cells by
minimizing the Eloss .
PMID- 29333765
TI - Ultrathin FeOOH Nanolayers with Abundant Oxygen Vacancies on BiVO4 Photoanodes
for Efficient Water Oxidation.
AB - Photoelectrochemical (PEC) water splitting is a promising method for storing
solar energy in the form of hydrogen fuel, but it is greatly hindered by the
sluggish kinetics of the oxygen evolution reaction (OER). Herein, a facile
solution impregnation method is developed for growing ultrathin (2 nm) highly
crystalline beta-FeOOH nanolayers with abundant oxygen vacancies on BiVO4
photoanodes. These exhibited a remarkable photocurrent density of 4.3 mA cm-2 at
1.23 V (vs. reversible hydrogen electrode (RHE), AM 1.5 G), which is
approximately two times higher than that of amorphous FeOOH fabricated by
electrodeposition. Systematic studies reveal that the excellent PEC activity
should be attributed to their ultrathin crystalline structure and abundant oxygen
vacancies, which could effectively facilitate the hole transport/trapping and
provide more active sites for water oxidation.
PMID- 29333764
TI - Education is the strongest socio-economic predictor of smoking in pregnancy.
AB - AIMS: To investigate socio-economic disparities in smoking in pregnancy (SIP) by
the mother's education, occupational class and current economic conditions.
DESIGN: Cross-sectional analysis with linked survey and register data. SETTING:
South-western Finland. PARTICIPANTS: A total of 2667 pregnant women [70% of the
original sample (n = 3808)] from FinnBrain, a prospective pregnancy cohort study.
MEASUREMENTS: The outcome was smoking during the first pregnancy trimester,
measured from the Finnish Medical Birth Register. Education and occupational
class were linked from population registers. Income support recipiency and
subjective economic wellbeing were questionnaire-based measures of current
economic conditions. These were adjusted for age, partnership status, residential
area type, parental separation, parity, childhood socio-economic background,
childhood adversities (the Trauma and Distressing Events During Childhood scale)
and antenatal stress (Edinburgh Postnatal Depression Scale). Logistic regressions
and attributable fractions (AF) were estimated. FINDINGS: Mother's education was
the strongest socio-economic predictor of SIP. Compared with university
education, adjusted odds ratios (aORs) of SIP were: 2.2 [95% confidence interval
(CI) = 1.2-3.9; P = 0.011] for tertiary vocational education, 4.4 (95% CI = 2.1
9.0; P < 0.001) for combined general and vocational secondary education, 2.9 (95%
CI = 1.4-6.1; P = 0.006) for general secondary education, 9.5 (95% CI 5.0-18.2; P
< 0.001) for vocational secondary education and 14.4 (95% CI = 6.3-33.0; P <
0.001) for compulsory schooling. The total AF of education was 0.5. Adjusted for
the other variables, occupational class and subjective economic wellbeing did not
predict SIP. Income support recipiency was associated positively with SIP (aOR =
1.8; 95% CI = 1.1-3.1; P = 0.022). Antenatal stress predicted SIP (aOR = 2.0; 95%
CI = 1.4-2.8; P < 0.001), but did not attenuate its socio-economic disparities.
CONCLUSIONS: In Finland, socio-economic disparities in smoking in pregnancy are
attributable primarily to differences in the mother's educational level (low
versus high) and orientation (vocational versus general).
PMID- 29333767
TI - [Clinical applications of periodontal gingival surgery.I: autogenous grafts].
AB - The field of periodontics has become increasingly discussed and advanced in
recent decades. The techniques of periodontal soft tissue grafts are among these
advancements. The techniques have been used more and more clinically not only in
periodontics, but also in the areas of dental implantology, aesthetics, and
orthodontics. In this article, we discuss the clinical indications and the
advantages and disadvantages of several autogenous tissue grafts (e.g. pedical
grafts, free gingival graft, and subepithelial connective tissue graft). These
techniques have made root coverage and the rebuilding of attached gingival
possible; therefore, it is necessary for all dentists to understand the
applications of periodontal soft tissue grafts.
PMID- 29333766
TI - [Relationship between different X-ray appearances and oral clinical
manifestations of cemental dysplasia].
AB - Cemental dysplasia is a non-neoplastic lesion and features different X-ray
appearances that easily confuse dentists. This condition is often observed in
conventional dental films or occasionally on panoramic radiographs. Cemental
dysplasia is easily misdiagnosed as chronic periapical periodontitis,
osteomyelitis, and tumor. In this paper, clinical mani-festations, imaging
diagnosis, and the correlation between these variables are analyzed to achieve
correct diagnosis.
PMID- 29333768
TI - [Effects of geranylgeranyltransferase I gene silencing by RNA interference on the
migration and invasion of tongue carcinoma].
AB - OBJECTIVE: RNA interference was used to silence geranylgeranyltransferase
I(GGTase-I) in vitro and to study the effect of GGTase-I on the migration and
invasion of tongue squamous cancer cells. METHODS: Three small interfering RNAs
(siRNA) were designed according to the GGTase-I sequence by Genebank and were
transfected into tongue squamous cancer cells Cal-27 to knock down GGTase-I
expression. The tested cells were divided into three groups, as follows: the RNA
interfered groups (GGTase-I siRNA1, GGTase-I siRNA 2, GGTase-I siRNA 3), a
negative control group (disrupted by random sequence NC-siRNA), and a blank
control group. GGTase-I and RhoA gene expressions were examined by quantitative
real-time polymerase chain reaction (qRT-PCR) and Western blot. The optimum
interference group was screened by qRT-PCR and Western blot and was assigned as
the experimental group. Matrix metalloproteinase (MMP)-2 and MMP-9 protein
expressions were examined by Western blot. GTP-RhoA expression of protein was
examined by GST-pull down. The migration and invasion abilities were analyzed by
wound healing assay and Transwell motility assay. RESULTS: GGTase-I mRNA and
protein expression in Cal-27 decreased significantly after transfection of GGTase
I siRNA (P<0.05). No significant difference of RhoA gene expression was detected.
MMP-2, MMP-9, and GTP-RhoA protein expressions decreased significantly (P<0.05).
The migration and invasion abilities were inhibited (P<0.05). CONCLUSIONS: To
inhibit GGTase-I expression, the migration and invasion abilities of tongue
squamous cancer cells should also be inhibited. Further studies on GGTase-I may
provide novel effective molecular targets for tongue squamous cancer cells.
PMID- 29333769
TI - [Significance of the expression of proliferating cell nuclear antigen and P53 in
the regeneration process of an atrophic parotid gland].
AB - OBJECTIVE: This research aims to further explore the expression and significance
of proliferating cell nuclear antigen (PCNA) and P53 in regenerating rat atrophy
parotid gland from the gene and protein levels. METHODS: One hundred and two
Wistar rats were randomly divided into experimental and control groups; the
former group's duct was ligated and then released respectively in 7 (Group A) and
14 days (Group B). Fresh parotid specimens were obtained at 0, 3, 5, 7, 10, 14,
21, and 28 days after being released. Hematoxylin-eosin staining method was used
to observe the morphological changes of the parotid gland. The significance of
P53 and PCNA in two groups was resolved by real-time fluorescence quantitative
polymerase china reaction and Western blot. RESULTS: Acinar cells aoptosis and
duct cells proliferation occurred when the occlusion of the parotid duct was
reversed on days 7 and 14. The expression of P53 was higher than that of PCNA,
and they reached the peak at the third and fifth days after groups A and B
regenerated, respectively. This finding was significantly different compared with
the control (P<0.01). P53 and PCNA contents decreased gradually; acinar and duct
gradually returned to normal morphology; PCNA and P53 contents gradually close to
the normal control group. CONCLUSIONS: After ligating the parotid duct, P53 was
highly expressed, and induced parotid gland atrophy. Mean-while, PCNA was highly
expressed, which then decreased inducing gland recovery.
PMID- 29333770
TI - [Construction of srtA-deletion mutant of Streptococcus mutans by an in-frame
deletion system].
AB - OBJECTIVE: To construct srtA-gene deletion mutant of Streptococcus mutans (S.
mutans) UA159 with IFDC2 cassette through overlapping polymerase chain reaction
(PCR) and allelic homologous recombination. METHODS: First, the upstream and
downstream fragments surrounding the srtA and IFDC2 cassette were PCR amplified
and ligated through overlapping PCR. The resulting amplicon was transformed into
UA159, and positive transformants were selected on BHI plates containing
erythromycin. Second, upstream and downstream fragments of srtA with overlap
regions were generated by PCR and were overlapped to create upDelta-down
amplicon. Then, the upDelta-down amplicon was transformed into the aforementioned
positive transformants and selected on BHI plates containing p-Cl-Phe. RESULTS:
The PCR analysis and DNA sequencing results indicated that the coding region of
the srtA was completely deleted, and the upstream and downstream regions flanking
the srtA were ligated seamlessly. CONCLUSIONS: The markerless srtA-deletion
mutant of S. mutans was constructed successfully, which laid a foundation for
further study of its biological function and influence on the biofilm formation
of S. mutans.
PMID- 29333771
TI - [Effect of hydrofluoric acid concentration on the surface morphology and bonding
effectiveness of lithium disilicate glass ceramics to resin composites].
AB - OBJECTIVE: This study aimed at determining the influence of hydrofluoric acid
(HF) in varied concentrations on the surface morphology of lithium disilicate
glass ceramics and bond durability between resin composites and post-treated
lithium disilicate glass ceramics. METHODS: After being sintered, ground, and
washed, 72 as-prepared specimens of lithium disilicate glass ceramics with
dimensions of 11 mm*13 mm*2 mm were randomly divided into three groups. Each
group was treated with acid solution [32% phosphoric acid (PA) or 4% or 9.5% HF]
for 20 s. Then, four acidified specimens from each group were randomly selected.
One of the specimens was used to observe the surface morphology using scanning
electron microscopy, and the others were used to observe the surface roughness
using a surface roughness meter (including Ra, Rz, and Rmax). After treatment
with different acid solutions in each group, 20 samples were further treated with
silane coupling agent/resin adhesive/resin cement (Monobond S/Multilink Primer
A&B/Multilink N), followed by bonding to a composite resin column (FiltekTM Z350)
with a diameter of 3 mm. A total of 20 specimens in each group were randomly
divided into two subgroups, which were used for measuring the microshear bond
strength, with one of them subjected to cool-thermal cycle for 20 000 times.
RESULTS: The surface roughness (Ra, Rz, and Rmax) of lithium disilicate glass
ceramics treated with 4% or 9.5% HF was significantly higher than that of the
ceramic treated with PA (P<0.05). The lithium disilicate glass ceramics treated
with 9.5% HF also demonstrated better surface roughness (Rz and Rmax) than that
of the ceramics treated with 4% HF. Cool-thermal cycle treatment reduced the bond
strength of lithium disilicate glass ceramics in all groups (P<0.05). After cool
thermal cycle, the lithium disilicate glass ceramics treated with HF had higher
bond strength than that of the ceramics treated with PA. The lithium disilicate
glass ceramics treated with 4% HF had higher bond strength than that of the
ceramics treated with 9.5% HF (P<0.05). During cool-thermal cycle, the lithium
disilicate glass ceramics treated with 4% HF demonstrated higher reduction in
bond strength than that of the samples treated with 9.5% HF (P<0.05).
CONCLUSIONS: The concentration of HF significantly affected the surface
morphology of lithium disilicate glass ceramics and the bond durability between
resin composites and post-treated lithium disilicate glass ceramics. The bond
strength between resin composites and post-treated lithium disilicate glass
ceramic was more efficiently maintained by treatment with 9.5% HF.
PMID- 29333772
TI - [Effect of different surface processes on the bond strength between zirconia
framework and veneering ceramic].
AB - OBJECTIVE: To compare the effect of different surface processes on bond strength
and microscopic structure using a scanning electron microscope (SEM) and an
energy distribution spectrum (EDS) at the bonding interface between zirconia
framework and veneering ceramic. METHODS: WIELAND zirconia core material was cut
into 33 rectangular specimens and fired on into rectangular specimens (10 mm*5
mm*5 mm). The specimens were randomly divided into three groups (n=?11). The
sandblasting group was sandblasted before firing. The sandblasting and liner
coverage group was sandblasted before firing and then sintered with liner
coverage after firing. The control group was not processed. All the veneering
ceramics (5 mm*?5 mm*5 mm) were fired on into the zirconia substructure by slip
casting technique. One bilayered specimen in each group was prepared for SEM and
EDS to examine the bonding conditions. The other specimens were measured for
shear force using an electronic universal dynamometer. The data obtained were
analyzed by using the statistical software SPSS 17.0. RESULTS: The values of the
shear bond strength test were (13.80+/-1.54) MPa for the control group, (18.06+/
0.59) MPa for the sandblasting group, and (21.04+/-1.23) MPa for the sandblasting
and liner coverage group. Significant differences existed among the three groups
(P<0.01). CONCLUSIONS: Abrasion before firing significantly increases the shear
bond strength of zirconia to veneering porcelain. The use of porcelain combined
with liner increases the shear bond strength.
PMID- 29333773
TI - [Influence of positional relationship between the long axis of the mandibular
anterior teeth and the alveolar bone on the treatment design of dental implants].
AB - OBJECTIVE: This study aimed at investigating and measuring the positional
relationship between the long axis of the mandibular anterior teeth and the
alveolar bone using cone beam computed tomography (CBCT) to provide reference
data for implant treatment. METHODS: From the CBCT image database, 150 cases of
radiographic data were selected according to the inclusion criteria and then were
divided into six groups: males' mandibular central incisors, males' mandibular
lateral incisors, males' mandibular canines, females' mandibular central
incisors, females' mandibular lateral incisors, and females' mandibular canines.
The angle (beta) formed by the long axis of the mandibular anterior teeth and the
corresponding alveolar bone was measured and recorded. Based on the long axis of
alveolar bone, if the teeth incline to the lingual side, the value of the angle
(beta) was positive; otherwise, the value was negative. The resultant data were
analyzed by SPSS 19.0. RESULTS: The beta of the mandibular central incisors
presented a mean value of 4.77 degrees (range: -8.17 degrees -16.10 degrees )
for male subjects and 5.38 degrees (range: -5.63 degrees -12.93 degrees ) for
female subjects. The beta of the mandibular lateral incisors exhibited a mean
value of 6.12 degrees (range: -2.87 degrees -?17.57 degrees ) for male subjects
and 5.81 degrees (range: -7.70 degrees -15.70 degrees ) for female subjects.
Finally, the beta of the mandibular canines presented a mean value of 5.01
degrees (range: -8.13 degrees -17.67 degrees ) for male subjects and 6.21
degrees (range: -7.70 degrees -17.87 degrees ) for female subjects. The
percentages of the beta between -10 degrees and 10 degrees of males' mandibular
incisors, mandibular lateral incisors, and mandibular canines were 87.34%,
80.67%, and 88.00%, respectively and those of females were 90.67%, 82.66%, and
82.66%, respectively. Whether male or female, the percentages of the beta between
-10 degrees and 10 degrees of the mandibular anterior teeth were more than 80%.
The beta that inclined to the lingual was not more than 20 degrees and to the
labial did not exceed 10 degrees . CONCLUSIONS: The long axis of the mandibular
anterior teeth was almost consistent with the long axis of the alveolar bone.
Therefore, the positional relationship could be referred to make reasonable
implants treatment plan.
PMID- 29333774
TI - [A cone beam computed tomography study on the anatomical position of accessory
mandibular foramina in Jiangxi adults].
AB - OBJECTIVE: This study used cone beam computed tomography (CBCT) to access the
distribution and position of accessory mandibular foramina in the mandibular body
of Jiangxi adults, and some safety rules of operation for clinics were provided.
METHODS: Two hundred CBCT image subjects of Jiangxi adults were selected, which
were divided into 4 groups by age with the same sex ratio. The number and
position of accessory mandibular foramina in mandibular anterior teeth, premolars
and molars region were described and the relationship between accessory
mandibular foramina incidence and factors of age, gender and lateral were
analyzed. RESULTS: A total of 1 123 accessory mandibular foramina were found,
with a mean of 5.62+/-2.10 per person. The accessory mandibular foramina
incidence decreased from the mesial region to the distal, and the lingual was
higher than the buccal. There was no significant difference in the number of
accessory mandibular foramina in male and female (P=0.195). However, the number
of accessory mandibular foramina was negatively correlated with age (r(s)=
0.301). Three highest frequency regions of accessory mandibular foramina were
mandibular symphysis area (98.0%), lingual alveolar area of lower medial (88.0%)
and lateral incisors and inferior area of lingual premolar (55.0%). CONCLUSIONS:
Accessory mandibular foramina are widely presented in the body of everyone's
mandible, addition attention should be paid to avoid the complications causing by
the damage of canal contents in the clinics.
PMID- 29333775
TI - [Effect of dexmedetomidine on emergence agitation after general anesthesia in
children undergoing odontotherapy in day-surgery operating room].
AB - OBJECTIVE: To study the effectiveness of dexmedetomidine used for general
anesthesia maintenance in children undergoing odontotherapy in day-surgery
operating room in reducing the incidence of emergence agitation (EA). METHODS:
Eighty children undergoing odontotherapy and under general anesthesia in day
surgery operating room were randomized into two groups, group A (n=40) and group
B (n=40). Each patient in group A was administered with a bolus dose of
dexmedetomidine (1.0 MUg.kg-1, saline diluted to 10 mL) pump-infused after
intubation and a maintenance dose of 0.1-0.4 mL.(kg.h)-1 followed-up until 45 min
before the end of operation. Each patient in group B was administered with a
bolus dose of normal saline 10 mL pump-infused after intubation and maintenance
dose of 0.1-0.4 mL.(kg.h)-1 followed-up until 45 min before the end of operation.
Gender, age, weight, physical status according to the American Society of
Anesthesiologists, perioperative heart rate (HR), mean arterial pressure (MAP),
pulse oxygen saturation (SpO2), sufentanil dosage, duration of surgery, time of
extubation, time of regaining consciousness, and time to reach modified Aldrete's
score>=12 were recorded. Behavior in postanesthesia care unit was rated on the
four-point agitation scale. RESULTS: Compared with group B, decreases were
observed in HR and MAP at the beginning of operation, in 10 and 30 min, 1 and 2 h
after the beginning of operation, and after extubation of group A (P<0.05).
Sufentanil dosage and incidence of EA during recovery of group A were also lower
than those of group B (P<0.05). Time to regain consciousness and time to reach
modified Aldrete's score>=12 of group A were longer than those of group B
(P<0.05). No statistical difference was observed between other indexes of the two
groups. CONCLUSIONS: As an anesthetic used for general anesthesia maintenance in
children undergoing odontotherapy in day-surgery operating room, dexmedetomidine
results in low incidence of EA during recovery and more stable vital signs.
PMID- 29333776
TI - [Clinical and microbiologic follow-up evaluations after non-surgical periodontal
treatment with Nd: YAG laser and scaling and root planning].
AB - OBJECTIVE: Our research aimed to detect the efficacy of non-surgical periodontal
treatment with Nd: YAG laser and scaling and root planning (SRP) for chronic
periodontitis. METHODS: We recruited chronic periodontitis patients who have more
than four teeth with clinical pocket depth of 4-8 mm. These teeth were
distributed in four different zones within the oral cavity. Moreover, the teeth
were single root teeth and not adjacent to each other. The subordinated teeth
were randomized into four groups, as follows: no treatment (C group), simple SRP
(SRP group), Nd: YAG laser after SRP treatment (SRP+L group), and SRP after Nd:
YAG laser treatment (L+SRP group). The four experimental observation points were
as follows: before treatment (baseline) and 1 week, 1 month, and 3 months after
treatment. We measured clinical indicators and collected subgingival deposits in
the four time points to analyze changes of red complex in periodontitis. RESULTS:
The clinical indicators were better in all treatment groups than in the control
group. Comparison among treatment groups indicated that the value of bleeding on
probing, periodontal probing depth, and clinical attachment loss showed no
difference. However, the value of plaque index in SRP+L and L+SRP presented a
significant reduction at 3 months after treatment. The percentages of
Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola in all
treatment groups decreased after clinical treatment, and differences were
observed among the treatment groups at different time points. CONCLUSIONS: Non
surgical periodontal treatment with SRP and Nd: YAG laser is not more effective
than SRP monotherapy. The sequence of laser treatment and SRP has no significant
effect on the treatment. However, SRP with Nd: YAG laser was beneficial for
plaque control. Non-surgical periodontal treatment with Nd: YAG laser may be used
as an alternative to reduce and control the proliferation of microorganisms in
persistent periodontitis, but it still needs further verification.
PMID- 29333777
TI - [Retrospective analysis of adverse drug reactions in stomatology hospital from
2014 to 2016].
AB - OBJECTIVE: This study aims to investigate the characteristics and general rules
of adverse drug reactions (ADR) in a 3A-grade stomatology hospital for safe and
rational drug use in clinical stomatology. METHODS: We retrospectively analyzed
52 ADR cases (1?1.36, males?females) reported in the West China Hospital of
Stomatology of Sichuan University from 2014 to 2016 in terms of gender and age
distributions, drug categories, and clinical manifestations. RESULTS: Eight kinds
of drugs and antibiotics were predominately used [24 cases, 46.15% (24/52)],
followed by nutrition drugs and antitumor drugs. Cephalosporin was the leading
antibiotic drug associated with ADR [20 cases, 83.33% (20/24)]. Intravenous
infusion was the most common route of drug administration [49 cases, 94.23%
(49/52)]. The most common manifestations of the ADR were damages of the skin and
its appendages and lesions of the digestive and nervous systems. CONCLUSIONS:
Strengthening the ADR monitoring system and further management should be
implemented to alleviate ADR in stomatology hospitals.
PMID- 29333778
TI - [Remineralization effect of casein phosphopeptide-amorphous calcium phosphate for
enamel demineralization: a system review].
AB - OBJECTIVE: This study aims to assess the remineralization effect of casein
phosphopeptide (CPP)-amorphous calcium phosphate (ACP) on enamel demineralization
by performing system review of randomized controlled trials (RCT) involving
the treatment of enamel demineralization with CPP-ACP. METHODS: The study
was developed based on the ?Cochrane handbook for systematic reviews of
interventions (Version 5.1.0) and included the following: search strategy,
selection criteria, data extraction, and risk of bias assessment. We
searched electronic databases such as PubMed, Embase, Cochrane Library, CNKI,
Wanfang and VIP up to September 2016. RCT of treating enamel
demineralization with CPP-ACP were included. Data extraction and domain
based risk of bias assessment were independently performed by two
reviewers. RESULTS: Twelve RCTs were included. Because of the difference of
experimental design and evaluation standards, the quantitative analysis can not
be carried out. CONCLUSIONS: There is no strong evidence that CPP-ACP is superior
to conventional fluoride formulations in enamel remineralization. However, due
to the limitations of sample size, follow-up time and study design, more high
quality and large-sample RCT are needed to further verify the evidence.
PMID- 29333779
TI - [Decalcified freeze-dried bone allograft combined with rich platelet derivatives
for the treatment of human periodontal intrabony defects: a Meta-analysis].
AB - OBJECTIVE: This review aims to systematically evaluate the effect of decalcified
freeze-dried bone allograft (DFDBA) combined with rich platelet derivatives on
the treatment of human periodontal intrabony defects. METHODS: A search in
PubMed, Web of Science, Embase, Cochrane Library, CNKI, and other electronic
databases was conducted to identify randomized controlled trials (RCT) of the use
of DFDBA combined with rich platelet derivatives in the treatment of human
periodontal intrabony defects, performed before May 2016. The quality of the RCTs
was assessed. RevMan 5.3 software was applied for Meta-analysis. RESULTS: A total
of nine RCTs were included. A total of 194 patients and 303 defects were
involved. Short-term (6 months) and long-term (12 to 18 months) groups were
included. Meta-analysis results revealed that DFDBA combined with rich platelet
derivatives was superior to DFDBA or rich platelet derivatives alone for probing
depth reduction in the short-term [MD=0.75 mm, 95% confidence intervals (CI)
(0.31 mm, 1.20 mm), P=0.001 0] and longterm groups [MD=0.87 mm, 95%CI (0.02 mm,
1.72 mm), P=0.04], clinical attachment level gain in the short-term [MD=?0.65 mm,
95%CI (0.08 mm, 1.22 mm), P=0.03] and long-term groups [MD=1.31 mm, 95%CI (0.60
mm, 2.01 mm), P<0.000 3], gingival recession reduction in the long-term group
[MD=-0.58 mm, 95%CI (-0.78 mm, -0.38mm), P<0.000 01], bone fill gain in the short
term [MD=0.52 mm, 95%CI (0.03 mm, 1.00 mm), P=0.04] and long-term groups [MD=1.26
mm, 95%CI (0.65 mm, 1.86 mm), P<0.000 1]. CONCLUSIONS: DFDBA combined with
platelet rich derivatives is probably effective in the treatment of human
periodontal intrabony defects. It is probably superior to DFDBA or platelet rich
derivatives alone. Considering the limitation of the included studies, high
quality and large-sample RCTs are required to evaluate the effect.
PMID- 29333780
TI - [Progress in exogenous factors affecting the growth and remodeling of condylar
process].
AB - Condyle is a critical growth region of the mandible where mandible by
endochondral ossification occurs. Condylar cartilage belongs to the secondary
cartilage, which is not only affected by genetic factors but also by stress, drug
intake, and other local factors. To promote the growth of the mandible, various
exogenous and local factors were used to alter the biological environment of the
condylar cartilage to stimulate endochondral ossification. This article reviews
studies on the influence of exogenous factors on condylar growth and
reconstruction. This literature review will provide a reference point for the
treatment of patients with mandibular retraction.
PMID- 29333781
TI - [Research progress on the relationship between triggering receptor expressed on
myeloid cells 1 and 2 and malignant tumors].
AB - Increasing scientific evidence supports the positive relationship between
inflammation and cancer development. The immune response initiated by pattern
recognition receptors is critical to triggering of tumor-associated inflammation.
Triggering receptor expressed on myeloid cells (TREM) is an immunoglobulin of the
super transmembrane glycoprotein family, which is mainly expressed on select
groups of myeloid cells. The most important members of TREM comprise TREM-1 and
TREM-2. Activation of TREM-1 and TREM-2 signaling is initiated upon binding of
their ligands. Subsequently, cross-linking reactions of downstream effectors
occur, resulting in inflammation regulation. Recently, the connection between
TREM and malignant tumors has been widely noticed and studied. This review
summarizes studies of association between TREM-1, TREM-2, and malignant tumors in
the medical field to provide new ideas for study on the correlation between
periodontitis and oral cavity cancer.
PMID- 29333782
TI - [Research advances on the molecular mechanism of autophagy regulated by
Porphyromonas gingivalis].
AB - Autophagy is an intracellular conservative degradation pathway. This event has
been considered as a key step in host defense against bacterial infection.
However, Porphyromonas gingivalis, as one of the evidence-sufficient periodontal
pathogens, can utilize self-induced autophagy to achieve persistent intracellular
survival and proliferation, which enable this organism to escape from host immune
surveillance. This review focuses on molecular mechanism of P. gingivalis
internalization and autophagy to illuminate its pathogenesis and to further
explore the relationship between P. gingivalis and systemic diseases.
PMID- 29333783
TI - [Application of preoperative vascular localization techniques for perforator
flaps].
AB - With the development of microvascular technology, perforator flaps have gradually
become a good alternative for reconstruction of tissue defects. However, the
major limitations of perforator flaps include uncertainty in predicting
anatomical location of perforators and high variability in perforator size and
course, which require preoperative localization techniques. Recently, as one of
the preoperative localization techniques, computed tomography angiography was
used to determine the number, size, course, and exact emerging point of
perforator flaps. Clinicians can reduce surgical complications and shorten
operative time by using computed tomography angiography. However, only several
studies reported clinical applications of computed tomography angiography. This
article reviews characteristics, classification, and preoperative location
techniques for perforator flaps and its problems.
PMID- 29333784
TI - [Ancient human jaw osteomyelitis in Chinese Yangshao period: a case report].
AB - This article reported jaw osteomyelitis in ancient human bone specimens, helping
us to understand the emergence of ancient human jaw osteomyelitis and other oral
health conditions.
PMID- 29333785
TI - [Decoronation management of the replacement resorption after delayed replantation
of avulsed teeth-case report with 4-year follow-up].
AB - Replacement resorption is the most frequent complication after delayed
replantation of avulsed teeth. The resorption can interfere with the development
of the alveolar ridge and lead to tilt of the adjacent teeth in growing patients.
However, there is no means of arresting or reversing the process. Recently
decoronation is recommended by International Assocaition of Dental Traumatology
as the optimal choice to manage it. This paper demonstrates the procedure and
effectiveness of the decoronation by literature review and a case report with 4
year follow-up.
PMID- 29333801
TI - Efficacy of the Regent Suit-based rehabilitation on gait EMG patterns in
hemiparetic subjects: a pilot study.
AB - BACKGROUND: The recovery of the functional limb mobility of patients with
cerebral damages can take great benefit of the role offered by proprioceptive
rehabilitation. Recently have been developed a special Regent Suit (RS) for
rehabilitative applications. Actually, there are preliminary studies which
describes the effects of RS on gait recovery of stroke patients in acute stage,
but none in chronic stage. Moreover, it is known that motor recovery does not
always reflect improvements of the muscle activity and coactivity. AIM: To
investigate the effects of proprioceptive stimulation induced by the Regent Suit
(RS) on the EMG patterns during gait in post-stroke chronic patients. DESIGN:
Randomized controlled trial. SETTING: S. Maugeri Foundation, Telese Terme (BN),
Italy. POPULATION: Patients have been randomly assigned into two equal groups of
20 patients: experimental group and traditional group. Further, a control group
of 20 healthy subjects have been enrolled. METHODS: The traditional group
attended a rehabilitation program composed by neuro-motor exercises without the
RS, the experimental group performed the same rehabilitation program while
wearing the RS. The NIH Stroke Scale (NIHSS), the Barthel Index (BI), the
Functional Independent Measure (FIM) and the Berg Balance Scale (BBS) have been
evaluated. EMG analysis has been performed considering the muscle activation
timing over the gait of the soleus, tibialis anterior, semitendinosus and vastus
lateralis muscles by decomposing the EMG signals into Gaussian pulses. Then, the
symmetry of muscle activation and the muscle synergy patterns over the gait cycle
have been assessed. RESULTS: The proprioceptive stimulation of the RS-based
treatment induces higher and remarkable restoration of the normal muscle
activation timing, also increasing the muscle symmetry and reducing the
pathological muscle coactivation on both affected and non-affected sides.
CONCLUSIONS: These results suggest confirm that a RS-based treatment is more
effective than usual care in improving the EMG patterns during locomotion and
daily living activities in chronic post-stroke subjects. CLINICAL REHABILITATION
IMPACT: The proprioceptive rehabilitation Regent Suit based has an impact on
motor function in stroke patients during gait.
PMID- 29333803
TI - Pediatric journals of the Southern Cone. Similarities and differences.
PMID- 29333802
TI - An upgraded model of teaching Physical and Rehabilitation Medicine: the vertical
education approach of Split University, Croatia.
PMID- 29333804
TI - Editors of biomedical journals and the disclosure of their own conflicts of
interest.
PMID- 29333805
TI - Bronchodilators in bronchiolitis: Yes or no?
PMID- 29333806
TI - ASQ-3: Validation of the Ages and Stages Questionnaire for the detection of
neurodevelopmental disorders in Argentine children.
AB - INTRODUCTION: The systematic assessment of child development in the first years
of life is an essential component of pediatric health checkups. The Ages and
Stages Questionnaire, third edition (ASQ-3) is the most validated scale, and has
been recommended by the UNICEF to verify if children have a normal neurological
development. It is a monitoring instrument to assess the main developmental
areas, including communication, gross motor, fine motor, personal-social, and
problem solving skills, and to compare the local population to the international
development standards. OBJECTIVE: To validate the ASQ-3 in a pediatric population
group. METHODS: Children aged 1-66 months were assessed at a public hospital by
pediatricians, psychologists, and educational psychologists. The SSPS software
package was used to determine population scales. RESULTS: In 630 children, who
had a homogeneous sex distribution, an 88% sensibility and a 94% specificity were
determined, with a positive predictive value of 88% and a negative predictive
value of 96%, compared to the National Screening Test (Prueba Nacional de
Pesquisa, PRUNAPE) and the cut-off scores for each age group. CONCLUSION: The ASQ
3 established that 19.5% of children were at risk of experiencing
neurodevelopmental disorders. The ASQ-3 met psychometric properties compared to
the PRUNAPE, which is the gold standard for the targeted and systematic
assessment of developmental milestones during health checkups in a rapid, simple
and cost-effective manner, so it was considered useful to monitor child
neurological development.
PMID- 29333807
TI - Contribution of diet to lead exposure among children aged 1 to 7 years in La
Plata, Buenos Aires.
AB - INTRODUCTION: Lead is a toxic metal which, even at low blood levels, can alter
normal neurodevelopment in children, so no blood lead level is acceptable. Lead
absorption from diet accounts for the highest contribution to blood lead levels
in the population who is not exposed to contaminated environments or because of
their occupation. The objective of this study was to determine the contribution
of diet to lead exposure among children aged 1 to 7 years who attended Hospital
de Ninos de La Plata for health check-ups. POPULATION AND METHODS: The study was
conducted between June 2015 and May 2016. A questionnaire on the frequency of
food intake was administered to 91 children whose average age +/- standard
deviation was 3.0 +/- 1.7 years, and foods included in the analysis were selected
based on this questionnaire. Selected foods were purchased from different
regional stores. Composite samples were made up of different food groups. Lead
levels corresponding to each food group were determined and, finally, the daily
intake of lead was estimated for the studied population. RESULTS: The daily
intake of lead was 138 ug/day. The food groups with the higher intake rates were
processed meat products (15.4%), bakery products (14.8%), milk (12.5%), and meat
(11.7%). CONCLUSIONS: Children aged 1 to 7 years attending a public hospital in
La Plata have a lead burden from dietary intake of 138 ug/day.
PMID- 29333808
TI - The perspective of primary health care pediatricians regarding childhood anemia
and iron supplementation.
AB - INTRODUCTION: Iron deficiency anemia is common in low- and middle-income
countries. According to the evidence, the impact of ferrous sulfate
supplementation in the pediatric population is low. Our objective was to analyze
the perspective of pediatricians regarding anemia and iron supplementation.
POPULATION AND METHODS: Qualitative, exploratory study. Semi-structured
interviews were conducted with primary health care pediatricians from Rosario.
Three core inquiry concepts were included: importance of this problem, clinical
practice, and representations about iron supplementation. The analysis consisted
in the systematization of the information collected by transcribing the recorded
interviews and notes. RESULTS: A total of 32 interviews were conducted. All
interviewees considered anemia was a relevant problem. At present, anemia is
associated with a poor-quality diet. Based on the findings, pediatric practice
follows national standards. There is consensus that low adherence is a barrier
for the clinical management of iron deficiency anemia. Pediatricians described
concepts that are potentially beneficial for the local setting, including
workshops on anemia and free provision of more flavorful iron supplements.
CONCLUSIONS: Iron deficiency anemia was considered a severe problem. In the
primary health care setting, outstanding interventions included workshops and
access to more flavorful iron supplements.
PMID- 29333809
TI - Assessment of orofacial pain management in a pediatric emergency department and
at home after discharge.
AB - INTRODUCTION: An inadequate pain management is common in the emergency
department. Our objective was to analyze pain management among children with an
orofacial infection or trauma in the emergency department and to assess
compliance and satisfaction with analgesia prescribed at discharge. POPULATION
AND METHODS: Cross-sectional, observational and analytical study in children
attending the emergency department for an orofacial infection or trauma over 2
months. Pain management in the emergency department, analgesia prescribed at home
and, following a call to parents, treatment provided and its adequacy to control
pain were registered. RESULTS: In total, 252patients (mean age: 4.5 years, SD:
3.89) were included. Pain assessment was recorded at the triage for 8.7%, and in
the medical report, for 3.6%. Analgesia was administered to 41.3% in the
emergency room. At discharge, no analgesia was prescribed to 13.9%; scheduled
analgesia, to 25.4%; and as needed, to 60.3%. Pediatricians prescribed scheduled
analgesia more frequently than surgeons (34.4% versus 16.5%, p < 0.01). At home,
no analgesia was administered to 39.3%; scheduled analgesia, to 36.1%; and as
needed, to 23%. There is little correlation between prescription at discharge and
at home (Kappa: 0.178). Analgesia was considered adequate in 84% of cases, and
was more frequent in trauma injuries than in infections (85.7% versus 14.3%, p <
0.01). CONCLUSIONS: Pain assessment and management was scarce in the emergency
department. The most common prescription was as needed, contrary to what is
recommended in the guidelines. Analgesic control worked better for trauma
injuries than for infections.
PMID- 29333810
TI - The value of acute phase reactants and LightCycler(r) SeptiFast test in the
diagnosis of bacterial and viral infections in pediatric patients.
AB - INTRODUCTION: This study was performed to investigate the value of acute phase
reactants and LightCycler(r) SeptiFast test to differentiate bacterial and viral
infections. POPULATION AND METHODS: Children with fever were enrolled to this
prospective study. Peripheral white blood cell (WBC), C-reactive protein (CRP)
and procalcitonin (PCT) were studied from all patients on day 1, 3 and 7. Blood
culture and chest X-ray were also obtained on day 1. Blood samples for
LightCycler(r) SeptiFast test were obtained in all patients to use them if there
was uncertain diagnosis between bacterial or viral infection. The patients were
divided into two groups as bacterial and viral infection. RESULTS: A total of 94
children with fever were enrolled. The mean value of fever was significantly
higher in bacterial group than viral group (p <0.001). In bacterial infection
group, 34 (72.3%) patients had negative blood culture. Of those, 12 (35.2%) had
positive SeptiFast test. There were no positive blood culture in patients with
viral infection group and all of them had negative SeptiFast test. The mean
levels of CRP on the first day of admission were significantly higher in
bacterial group than viral group (p <0.001). CRP and PCT levels of day 3 and 7
were significantly higher in bacterial group (p <0.001). The sensitivity and
specificity levels of WBC, CRP and PCT were 63.8%, 44.7%, 74.5% and 78.7% ,68.1%
and 100%, respectively. CONCLUSIONS: We found that acute phase reactants,
especially PCT, and LightCycler(r) SeptiFast test may help to differentiate
bacterial and viral infections.
PMID- 29333811
TI - Neonatal mortality and associated factors in newborn infants admitted to a
Neonatal Care Unit.
AB - INTRODUCTION: The increasing survival rate of preterm infants has altered the
epidemiology of neonatal diseases; however, neonatal mortality is still the main
component of child mortality. The objective of this study was to evaluate
neonatal mortality and associated factors in newborn infants admitted to a
neonatal care unit. MATERIAL AND METHODS: Prospective cohort study conducted
between January 2016 and January 2017 at Hospital Civil de Guadalajara "Dr. Juan
I. Menchaca." The incidence of deaths and associated conditions was evaluated
using a multivariate logistic regression analysis. RESULTS: A total of 9366 live
births were registered; 15% (n: 1410) of these were admitted to the neonatal care
unit. The mortality rate was 125.5 per 1000 hospitalized newborn infants (95%
confidence interval [CI]: 109-144); the main reasons for admission were
congenital malformations or genetic disorders (28.2%), infections (24.9%), and
respiratory distress (20.9%). The conditions associated with death were
gestational age < 37 weeks (OR: 2.41, 95% CI: 1.49-3.93), birth weight < 1500
grams (OR: 6.30, 95% CI: 4.15-9.55), moderate/severe respiratory distress at 10
minutes (OR: 1.89, 95% CI: 1.24-2.86), Apgar score < 7 at 5 minutes (OR: 9.40,
95% CI: 5.76-15.31), congenital malformations (OR: 5.52, 95% CI: 3.12-9.78), and
less than 5 antenatal care visits (OR: 1.51, 95% CI: 1.09-2.08). CONCLUSIONS:
Preterm birth, low birth weight, respiratory distress, Apgar score < 7,
congenital malformations, and a history of < 5 antenatal care visits were
associated with a higher risk for death.
PMID- 29333812
TI - Markers of inflammation and tolerance development in allergic proctocolitis.
AB - BACKGROUND: Today, as a result of an increase in the frequency of food protein
induced allergic proctocolitis (FPIAP), there is a need for studies not only to
enlighten the pathophysiology of the disease but also to determine simple, non
invasive markers in both diagnosis, and evaluation of the development of
tolerance. No study has been found in the literature about the place of
neutrophil/lymphocyte ratio (NLR) and mean platelet volume (MPV), which are easy
to calculate and non-invasive markers. OBJECTIVES: The purpose is to determine
the relation between NLR and MPV with the diagnosis and development of tolerance
in children with FPIAP. METHODS: In this retrospective cross-sectional study,
clinical, demographic symptoms and laboratory findings of patients, monitored
with FPIAP diagnosis in allergy and gastroenterology clinics, were acquired from
the patient record system. Hemogram values at the time of diagnosis were compared
with the values of healthy children of the same age and gender. RESULTS: Among 59
patients diagnosed with FPIAP, males constitute 47.4% and females constitute
52.6%. MPV and platelet crit (PCT) values were significantly high when compared
to the control group (n: 67) in FPIAP cases (p < 0.001). Also, MPV and PCT values
were significantly high in non-tolerance developing cases when compared to
developing ones (p= 0.01). CONCLUSIONS: Contrary to NLR, MPV and PCT values have
been considered to be good markers in predicting prognosis in cases with FPIAP
since they are quick, cost effective and easy to calculate.
PMID- 29333813
TI - Body composition and energy expenditure in a population of children and
adolescents with myelomeningocele.
AB - INTRODUCTION: Myelomeningocele is a congenital defect that occurs when the neural
tube fails to close completely. It causes body composition alterations and a high
prevalence of obesity. It is difficult to detect the most adequate indicator for
a nutritional diagnosis due to the impossibility of recording accurate
anthropometric measurements. OBJECTIVE: To describe body composition, resting
energy expenditure and metabolic disorders in a population of patients with
myelomeningocele managed at "Hospital Garrahan" by comparing obese patients with
myelomeningocele and a control population with multifactorial obesity. POPULATION
AND METHODS: An anthropometry, an impedance analysis, skinfold equations, arm
circumference equations, indirect calorimetry, and biochemical determinations
were done to all patients with myelomeningocele between June 2013 and April 2014,
once the informed consent had been signed. RESULTS: 131 patients aged 0.7-18.6
years were assessed; they were classified according to their body mass index Z
score into low weight (15%), normal weight (42%), overweight (12%), and obese
(31%). A high correlation (r: 20.74) was observed between the fat mass % measured
by impedance analysis versus that estimated using skinfolds. Patients with a high
fat mass % had a higher body mass index Z-score than those with a normal fat mass
% (1.07 versus -0.27, p: 0.0001) although both values were within normal
parameters. A lower resting energy expenditure was observed among obese patients
with myelomeningocele than predicted and in comparison with multifactorial obese
controls. CONCLUSIONS: A high percentage of overweight/obesity was found in the
population with myelomeningocele. Skinfold equations would be more adequate to
detect obesity. Obese patients with myelomeningocele had a lower resting energy
expenditure than predicted and in comparison with controls. Energy indication
should be customized.
PMID- 29333814
TI - Morbidity in congenital heart surgery in a public hospital in Argentina.
AB - OBJECTIVE: To describe the complications associated with heart surgery, compare
them to a reference population, and identify mortality risk factors. PATIENTS AND
METHODS: Retrospective and descriptive study. All patients who underwent surgery
at Hospital Garrahan in the 2013-2015 period were included. Age, weight,
procedure, mechanical ventilation, length of stay in days, morbidity, and course
were recorded. Renal failure requiring dialysis, neurological deficit, permanent
pacemaker, circulatory support, phrenic nerve or vocal cord palsy, reoperation,
wound infection, chylothorax, and tracheotomy were considered morbidities. A
descriptive, statistical analysis by risk category was done using the Society of
Thoracic Surgeons (STS) morbidity score. RESULTS: 1536 patients, median age: 12
months (interquartile range [IQR] 25-75: 3-60), weight: 8 kg (IQR 25-75: 4.4 to
17.5), mortality: 5%. A total of 361 events were recorded in 183 patients. An
unplanned reoperation was the most common event (7.2%); the rest occurred in < 3%
of patients. Compared to patients without complications, patients who had events
required more days on mechanical ventilation: 9.95 (IQR 25-75: 7.6512.24) versus
1.8 (IQR 2575: 1.46-2.14), p< 0.00001; a longer length of stay: 28.8 (IQR 25-75:
25.1-32.5) versus 8.5 (IQR 25-75: 7.9-9.2), p< 0.0001; and had a higher
mortality: 19.6% versus 3.1% (RR: 4.58, 95% CI: 3.4 to 6.0), p< 0.0001.
Circulatory support and renal failure were associated with a higher mortality.
CONCLUSIONS: An unplanned reoperation was the most common event. Patients with
complications required more days on mechanical ventilation and a longer length of
stay and had a higher mortality. Circulatory support and renal failure were
associated with a higher mortality.
PMID- 29333815
TI - Prevalence of vitamin K deficiency and associated factors in non-supplemented
cystic fibrosis patients.
AB - INTRODUCTION: Vitamin K deficiency is highly prevalent in cystic fibrosis (CF)
patients despite supplementation. Moreover, no reliable risk factors for its
occurrence are known. The aim was to assess the prevalence of vitamin K
deficiency and associated factors in non-supplemented CF patients. METHODS:
Prothrombin concentration induced by vitamin K absence (PIVKA-II) and the
undercarboxylated osteocalcin percentage (u-OC) were determined. In all patients
clinical status was assessed and its relation to vitamin K deficiency determined.
The following tests were used for statistical analysis: Mann-Whitney test, ANOVA
test or the Kruskal Wallis test, the chi-squared test or the Fisher-Freeman
Halton test, and multiple linear and multiple forward stepwise logistic
regression analysis. RESULTS: The study group comprised 79 CF patients aged 0.4
25.3 years. PIVKA-II and u-OC were abnormal in 56 (70.9%) and 45 (57.0%)
patients. Patients with elevated PIVKA-II were significantly older (p= 0.0184)
and had lower Z-score values for body weight (p= 0.0297) than those with normal
concentrations. Patients with normal or pathological u-OC percentage did not
differ. Abnormal PIVKA-II and u-OC were reported more frequently in subjects with
two severe CFTR mutations and with worse/poor nutritional status. Multiple linear
and forward stepwise regression analyses did not reveal strong predictive factors
of vitamin K deficiency. CONCLUSION: Vitamin K deficiency is highly prevalent in
the natural course of cystic fibrosis. There are no reliable clinical
determinants of its occurrence.
PMID- 29333816
TI - National Health Care Network for children with oral clefts: organization,
functioning, and preliminary outcomes.
AB - INTRODUCTION: Oral clefts are major congenital anomalies that may affect the lip
and/or palate, and that may also involve the nose and nostrils. In Argentina,
their prevalence is approximately 15 per 10 000 births. In 2015, the Ministry of
Health of Argentina created a national health care network for children with oral
clefts in Argentina through the joint work with the National Registry of
Congenital Anomalies (Red Nacional de Anomalias Congenitas, RENAC) (coordinating
center for the national network) and the SUMAR Program. The objective of this
study was to describe the health care network and its preliminary outcomes.
POPULATION AND METHODS: A total of 61 centers that provided a comprehensive
treatment for oral clefts or in collaboration with other centers were identified
and accredited. Maternity centers were connected with treating centers grouped in
health care network nodes. RESULTS: In the period between March 2015 and February
2016, 550 newborn infants who were exclusively covered by the public health care
system were identified. Among these, 18% had a cleft lip; 62%, cleft lip and
palate; and 20%, cleft palate only; 75% were isolated cases and 25%, in
association with other congenital anomalies. CONCLUSION: Approximately 70% of
children were assessed by a certified treating institution and are receiving
treatment. The network seeks to improve data systematization, include the largest
number of centers possible, strengthen interdisciplinary team work, and promote
high-quality standards for treatments.
PMID- 29333817
TI - Anthropometric and biochemical assessment of nutritional status and dietary
intake in school children aged 6-14 years, Province of Buenos Aires, Argentina.
AB - INTRODUCTION: Childhood obesity is a global epidemic. School age and adolescence
are critical stages for the implementation of eating and lifestyle habits.
OBJECTIVE: To assess anthropometric and biochemical assessment of nutritional
status and dietary intake in children, their relationship with socioeconomic
factors and georeferencing. METHODS: Cross-sectional study in schoolchildren aged
6-14 years from the District of General Pueyrredon, during August-November 2013.
Dietary intake was assessed using a 24-hour dietary recall interview, and
georeferencing was done using the gvSIG software. RESULTS: A total of 1296
children were included for anthropometric and socioeconomic assessment. A sub
sample included 362 children for intake and biochemical parameters. Overweight
was observed in42.97% (95% confidence interval [CI]: 40.3-45.7) and obesity, in
18.5% (95% CI: 16.320.5). Breakfast was related to a lower risk for overweight
(OR: 0.7, 95% CI: 0.5-0.9) and obesity (OR: 0.7, 95% CI: 0.5-0.9). Attending high
school was related to a lower prevalence of weight excess (OR: 0.45, 95% CI: 0.3
0.7); male sex posed a higher risk for obesity (OR: 1.7, 95% CI: 1.3-2.3). Also,
4.44% of participants had anemia; 19.6%, hypercholesterolemia; and 21.3%,
hypertriglyceridemia. Lipid and saturated fat intake was high, whereas dietary
cholesterol and fiber intake was low. Geographic distribution was homogeneous.
CONCLUSIONS: The prevalence of overweight was high. The risk for obesity was
higher among boys; breakfast appeared as a protective factor against
overweight/obesity. A low-fiber and high-fat intake, and high blood cholesterol
and triglyceride levels reveal that overnutrition is a prevalent public health
problem.
PMID- 29333819
TI - Hashimoto's disease in a cohort of 29 children and adolescents. Epidemiology,
clinical course, and comorbidities in the short and long term.
AB - Hashimoto's thyroiditis is the most common cause of goiter and hypothyroidism
among children and adolescents. Its clinical manifestations and course vary. The
objective of this study was to review the clinical and evolutionary
characteristics of Hashimoto's disease in the pediatric population. Clinical,
analytical, ultrasound, epidemiological, and evolutionary data of patients with
autoimmune thyroiditis seen at Hospital Universitario San Juan de Alicante
between January 2010 and January 2016 were analyzed. A total of 29 patients were
included in the study. A higher prevalence of girls was observed, at a 2:1 ratio.
The main reason for consultation was the accidental detection of high thyroid
stimulating hormone levels or positive anti-thyroid antibodies in a lab test done
for other reason. In the initial analysis, 53.3% of patients had subclinical
hypothyroidism and only 10% of them had frank hypothyroidism. Two patients
developed thyroid cancer.
PMID- 29333818
TI - Community-acquired methicillin-resistant Staphylococcus aureus infections:
hospitalization and case fatality risk in 10 pediatric facilities in Argentina.
AB - INTRODUCTION: Community-acquired methicillin-resistant Staphylococcus aureus (CA
MRSA) infections are prevalent both in Argentina and worldwide, and they may have
a severe clinical course. OBJECTIVES: To estimate the hospitalization rate and
case fatality risk factors of CA-MRSA infection. METHODS: Cross-sectional,
analytical study. All patients < 15 years old with community-acquired
Staphylococcus aureus (CA-SA) infections admitted to 10 pediatric facilities
between January 2012 and December 2014 were included. RESULTS: Out of 1141
patients with CA-SA, 904 (79.2%) had CA-MRSA. The rate of hospitalization of CA
MRSA cases (per 10 000 discharges) among patients < 5 years old was 27.6 in 2012,
35.2 in 2013, and 42.7 in 2014 (p = 0.0002). The 2-4-year-old group was the most
affected one: 32.2, 49.4, and 54.4, respectively (p = 0.0057). The clinical
presentations included skin and soft tissue infections: 66.2%, pneumonia: 11.5%,
sepsis/bacteremia: 8.5%, osteomyelitis: 5.5%, arthritis: 5.2%, psoas abscess:
1.0%, pericarditis/endocarditis: 0.8%, meningitis: 0.6%, and other: 0.7%. In
terms of antibiotic resistance, 11.1% had resistance to erythromycin; 8.4%, to
gentamicin; and 0.6%, to trimethoprim-sulfamethoxazole. All strains were
susceptible to vancomycin. The case fatality rate was 2.2% and associated risk
factors were (odds ratio [95% confidence interval]) age > 8 years (2.78, 1.05
7.37), pneumonia (6.37, 2.3717.09), meningitis (19.53, 2.40-127.87), and
sepsis/bacteremia (39.65, 11.94-145.55). CONCLUSIONS: The rate of CA-MRSA
infection was high; the rate of hospitalization increased in the 2013-2014
period; the 2-4-year-old group was the most affected one. A higher case fatality
risk was observed among patients > 8 years old and those with the clinical
presentations of pneumonia, meningitis, and sepsis.
PMID- 29333820
TI - Osteomyelitis in burn children: Ten years of experience.
AB - INTRODUCTION: Osteomyelitis is uncommon among burn patients. OBJECTIVE: To
describe the clinical, microbiological, and evolutionary characteristics of burn
children with osteomyelitis hospitalized in a tertiary care facility. METHODS:
Retrospective and descriptive study conducted between January 2007 and January
2017. RESULTS: Out of 600 burn children, 12 developed osteomyelitis (incidence:
2%). Eleven patients had a burn caused by direct fire. Patients' median age was
42.5 months (interquartile range [IQR]: 27-118 months), and their median burned
surface area was 33.5% (IQR: 18.5-58%). Osteomyelitis was diagnosed at a median
period of 30 days following the burn injury. The most common locations were the
upper limbs and the cranial vault. Fever was the most frequent clinical
manifestation. The most common microorganisms isolated in bone tissue were fungi
in 9 patients. All showed compatible anatomopathological findings. The treatment
lasted a median of 44.5 days (IQR: 34.5-65.5 days). Six patients had motor
sequelae and 1 died. CONCLUSION: Fungal osteomyelitis was the most commonly
observed etiology. Half of patients had functional sequelae and only 1 patient
died.
PMID- 29333822
TI - Labial adhesions: Experience in a children's hospital.
AB - Labial adhesions are defined as the complete or partial fusion of the pudendal
cleft due to the agglutination of the labia minora in the midline. They most
commonly occur between 3 months and 6 years of life. Between January 1st, 2002
and December 31st, 2015, 425 girls diagnosed with labial adhesions and seen at
the Unit of Pediatric and Adolescent Gynecology of Hospital de Ninos de La Plata,
Argentina, were analyzed. Their average age was 2.7 years (standard deviation:
2.6 years). The most common presentation of labial adhesions was that involving
more than 75% of the total length of the labia (p < 0.0000001). A total of 84.2%
of patients showed no symptoms and 4% had urinary symptoms. Also, 68.4% of the
girls who had a history of urinary tract infection had labial adhesions with a
length of involvement of > 75%. Finally, 90.6% of cases resolved with topical
estrogens; and 2.1% had adverse events.
PMID- 29333821
TI - Opioid treatment for mixed pain in pediatric patients assisted by the Palliative
Care team. Five years of experience.
AB - Pain is defined as an unpleasant sensory and emotional experience associated with
actual or potential tissue damage. Depending on its pathophysiological mechanism,
it may be classified into nociceptive, neuropathic, and mixed pain. If pain is
moderate to severe, a strong opioid should be administered and, when this is the
case, morphine is the drug of choice. If morphine is ineffective or causes
intolerable adverse effects, opioid rotation is recommended. Our objective was to
describe the drug management for mixed pain used in patients assisted by the
Palliative Care team of Hospital General de Ninos Pedro de Elizalde between
August 2011 and September 2015. A total of 72 patients were included. Their mean
age was 10.1 years, and the most common underlying disease was cancer. The
initial opioid was morphine in 57 cases; 48 patients received adjuvant drugs.
Opioid rotation was indicated in half of cases, and the most common switch was
from morphine to methadone.
PMID- 29333824
TI - Eosinophilic esophagitis and esophageal atresia: coincidence or causality?
AB - Eosinophilic esophagitis is an immune-mediated chronic disease of the esophagus
characterized by symptoms related to esophageal dysfunction and tissue
eosinophilia. In the endoscopy, the esophageal mucosa may appear normal or show
exudates, rings, edema, furrows, and strictures. Its management is based on
elimination diet, topical corticosteroids and/or esophageal dilation. Atresia is
the most common congenital alteration of the esophagus; it requires surgical
repair and poses potential complications, such as gastroesophageal reflux,
strictures, and esophageal dysmotility. Up to 2015, 48 cases of eosinophilic
esophagitis and esophageal atresia were reported, with dysmotility, reflux, and
long-term acid suppression involvement. Prevalent clinical signs include
dysphagia, difficulty eating, and reflux symptoms, so an
esophagogastroduodenoscopy with biopsy is recommended to rule out associated
eosinophilic esophagitis in patients with esophageal atresia and persistent
symptoms before performing an esophageal dilation and/or anti-reflux surgery. If
eosinophilic esophagitis is confirmed, it should be managed with the
corresponding drugs, and the subsequent therapeutic approach will depend on its
clinical course.
PMID- 29333823
TI - Brain death and organ donation in Argentine pediatric intensive care units. A
multicenter study.
AB - Brain death (BD) is a condition determined by the complete and irreversible
absence of brain functions. Maintenance of vital functions creates an opportunity
for organ donation. A retrospective study was carried out in 7 pediatric
intensive care units of Argentina (from 1/1/2013 to 9/30/2016) to determine the
incidence of clinical and certified BD, and the proportion of effective
transplantations. Among deceased patients, 19.14% (147/768) met the clinical
requirements for BD, and the main cause of BD was multiple trauma. BD was
certified in 13.4% of deceased patients (103); an electroencephalogram and an
apnea test were the most commonly used ancillary methods. Organ maintenance time
was 24 hours. A total of 87 families were approached for donation; 59 were
rejected (they were not suitable or refused). Effective donors accounted for 25%
(26/103) of patients with certified BD and 72 patients received solid organs.
PMID- 29333825
TI - 6 minutes.
AB - At present, there is a trend towards reducing the duration of office visits. In
some regions of Spain, it has been set at 6 minutes per patient. This impacts on
several levels: literally, many times it is impossible to complete the medical
act; at an emotional level, because there is little possibility to establish an
adequate doctor-patient relationship; and symbolically, for considering that the
main aspects of humane health care are expendable. This takes place in a society
that tends to see health care as a merchandise subject to market rules that gives
priority to the immediate over the important. Patients, physicians, and managing
authorities are participants of this change which negatively affects current
medical practice. The increase in unnecessary additional testing, avoidable
treatments, the costs of iatrogenesis, a lower treatment adherence, and
unnecessary reconsultations are proven consequences. In the field of pediatrics,
this increases the risk of losing screening opportunities in critical areas.
PMID- 29333826
TI - Vitamin D deficiency in pediatric clinical practice.
AB - INTRODUCTION: Vitamin D research suggests it has a role in disorders other than
bone metabolism. OBJECTIVE: To update the information on vitamin D deficiency
(VDD) in pediatric clinical disorders. METHODS: Search in virtual libraries,
giving priority to clinical and longitudinal studies and meta-analyses on VDD in
the pediatric age group published in the past 20 years. The terms "vitamin D
deficiency", "children and adolescents" (both in Spanish and English) were used
as search descriptors. RESULTS: In the pediatric population, VDD is associated
with different clinical diseases, such as bone alterations, insulin resistance,
metabolic syndrome, respiratory tract infections, asthma, and autoimmune
diseases. Besides, it is associated with prematurity, obesity, malabsorption, use
of anticonvulsant agents, and lifestyle characteristics, such as clothing,
extreme latitudes, low consumption, and little sun exposure. CONCLUSIONS:
According to the evidence, VDD is highly prevalent in several disorders and
diseases in the pediatric age group. The recommendation is to prevent VDD in risk
conditions and to maintain 25(OH)D serum levels > 75 nmol/L.
PMID- 29333827
TI - Rectus sheath hematoma in a macrosomie neonate following difficult delivery. Case
report.
AB - Macrosomia is a risk factor for birth injuries and is associated with neonatal
morbidity and mortality. Cephalohematoma and clavicular fracture are the most
frequent birth injuries. Intraabdominal injuries are uncommon birth injuries.
Rectus sheath hematoma (RSH) is an accumulation of blood in the sheath of rectus
abdominis muscle. It is associated with trauma, operations and anticoagulant
therapy, especially in adults and elders. We present a macrosomic male neonate
with difficult vaginal delivery, who had in the physical examination periumblical
ecchymose of 1x1 cm and a parietal cephalohametoma of 1x1 cm. The abdominal
ultrasonogram and the computed tomography scan of the abdomen showed a 7x4x2 cm
right rectus sheath hematoma.
PMID- 29333828
TI - [Congenital Horner syndrome. Case report].
AB - Horner syndrome is characterized by the following triad of clinical signs:
miosis, ptosis and facial anhidrosis. In addition, iris heterochromia,
conjunctival injection, facial erythema, congestive nasal mucosa and apparent
enophthalmos secondary to the reduction of the palpebral fissure can appear. It
is caused by an interruption of the sympathetic pathway that extends from the
hypothalamus to the orbit. Because there is no decussation, the signs are
homolateral to the lesion. Traditionally, it is classified as congenital and
acquired. Occasionally, it is associated with neoplasias such as neuroblastoma.
It remains controversial what imaging studies should be requested as a
protocolized workup of this neurological syndrome in a patient. We report the
case of a 45-day-old infant with congenital Horner syndrome.
PMID- 29333829
TI - [Galactosialidosis: a new "de novo" mutation in CTSA gene in a patient with late
infantile galactosialidosis].
AB - Galactosialidosis (OMIM #256540) is an autosomal recessive lysosomal storage
disorder caused by mutations in the CTSA gene, which encodes the protective
protein cathepsin A. The loss of function of this protein causes a secondarily
deficiency of beta-galactosidase and N-acetyl-a-neuraminidase enzymes activities.
We describe the clinical, biochemical and molecular analysis of a case report
with a phenotype compatible with the late infantile form. The biochemical
analysis reveled deficiencies of beta-galactosidase and neuraminidase activities
in dried blood spot and fibroblasts and the molecular study showed two missense
mutations in the CTSA gene: a previously reported mutation, p.Arg441Cys
(c.1321C>T), and a novel mutation, p.His475Pro (c.1424 A>C), located in exons 14
and 15, respectively.
PMID- 29333830
TI - [Treatment with sublingual desmopressin in two infants with hydranencephaly and
central diabetes insipidus].
AB - Central diabetes insipidus is a rare disease in children caused by a deficiency
of vasopressin. Its main clinical manifestations are polyuria and polydipsia.
Brain malformations are one of the main causes. Desmopressin is the synthetic
drug of choice for the treatment. One of the routes of administration is
sublingual and its use in infants is very limited. We describe two infants with
central diabetes insipidus and hydranencephaly who were successfully treated with
sublingual desmopressin.
PMID- 29333831
TI - [Mammary hemangioma in an infant with apparent mastitis. Case report].
AB - Mammary pathology is infrequent during childhood. It is rare the probability of
finding a breast mass in an infant. The most frequent possible diagnoses at this
age are breast abscess, mastitis, breast engorgement due to maternal hormonal
stimulation and hemangioma. Reaching the proper diagnosis is essential in order
to apply a suitable treatment and avoid the potential disease complications. We
present the case of a female infant having a mass in the right breast from birth.
Initially the entity was treated as mastitis. Nevertheless, the bad evolution
made necessary considering the differential diagnosis. It was concluded to be a
hemangioma. Due to the lesion ulceration and the potential risk of developing
breast hypoplasia, treatment with propranolol was started. The tumor was almost
completely resolved.
PMID- 29333832
TI - An incidentally detected anomalous origin of the right coronary artery from the
pulmonary artery in an infant.
AB - Isolated anomalous origin of the right coronary artery from the main pulmonary
artery is a rare congenital anomaly, and few cases have been reported in the
pediatric age group. Here in, we report an asymptomatic case of a 2-month-old
male infant who has been diagnosed as anomalous origin of the right coronary
artery from the main pulmonary artery during the evaluation for cardiac
abnormalities. For a suspicion on echocardiography, cardiac catheterization and
coronary angiography performed to verify the diagnosis of anomalous origin of the
right coronary artery from the main pulmonary artery. The patient underwent
surgery and did well after two months follow up. Early diagnosis may prevent
patients from cardiovascular complications.
PMID- 29333833
TI - [Infrequent mutation in renal-coloboma syndrome: case report and review].
AB - Renal-coloboma syndrome is an autosomal dominant disease characterized by renal
hypodysplasia and coloboma. A case of a 12-year-old girl with chronic kidney
disease, bilateral optic nerve colobomas and an exceptional PAX-2 gene mutation
is presented. Diagnosed in prenatal scans with bilateral renal hypoplasia, she
presented clinical and laboratory findings of chronic kidney disease at 5 days of
life. Following tests showed grade II bilateral vesicoureteral reflux
spontaneously solved, maintained non nephrotic proteinuria controlled with
enalapril and bilateral colobomas with left macular atrophy. Renal function
remained stable. Genetic study showed de novo and non sense mutation p.R104X in
heterocygosis. Currently there are 80 published cases of renal-coloboma syndrome
associated with this gene mutations. Ophthalmologic and genetic evaluations are
crucial in cases affected by renal hypodysplasia. Renal function will establish
prognosis. We review the etiopathogenesis of this disease.
PMID- 29333834
TI - [Congenital esophageal stenosis: diagnosis and treatment. Cases review].
AB - Congenital esophageal stenosis is a very rare condition and there is no standard
treatment. We report the diagnosis, treatment and outcome of 11 patients with
this condition managed at our institution. The most common symptom was dysphagia.
The age at diagnosis was between 1 day and 14 years (mean age: 4.7 years). The
esophagogram confirmed the diagnosis. Five patients presented associated
anomalies. Four patients received surgical treatment and 7 only balloon
dilatations. Pathologic examinations showed 3 fibromuscular stenosis and one with
tracheobronchial remnants. All patients had a good outcome with a mean follow up
of 4.5 years. Balloon dilatations were the definitive treatment in most of the
patients.
PMID- 29333835
TI - [An unintended diagnosis: Serotonergic toxicity secondary to drug interactions.
Case reports].
AB - Serotonin toxicity is a potentially life-threatening condition associated with
increased serotonergic activity in the central nervous system. It is seen with
therapeutic medication use, intentional self-poisoning and inadvertent
interactions (SSRI-isoniazid). Although this pathology is increasingly common, it
is not well recognized by physicians and manifestations may be wrongly attributed
to another cause. The aim of this paper is to describe the clinical picture of a
patient, to collaborate on diagnosis and to improve medical care of these
patients.
PMID- 29333836
TI - [Phakomatosis pigmentovascularis cesioflammea: a case report].
AB - Phakomatosis pigmentovascularis (PPV) is a syndrome characterized by the
association of a vascular nevus with a congenital pigmented lesion (epidermal
nevus, nevus spilus, and dermal melanocytosis). There are different types of PPV
according to the pigmentary nevus associated with the vascular malformation.
Patients may present only the cutaneous condition or have systemic
manifestations, among them, trauma, neurological and ophthalmological disorders.
We report the case of a 1-year-old girl who had congenital glaucoma. On
examination, we identified facial paralysis, bilateral ocular melanosis,
segmental capillary vascular malformation on the face as on left trunk and
extremities, and aberrant Mongolian spots on the upper back, lumbosacral area and
buttocks. Due to clinical manifestation, the diagnosis of PPV was made. The
patient was evaluated by Neurology, Traumatology and keeps on with
ophthalmological controls. Complementary studies are important, to rule out
extracutaneous manifestations in PPV.
PMID- 29333837
TI - [Biodegradable airway stent for the treatment of bronchial obstruction in the
child. Case report].
AB - Bronchial obstruction is infrequent in the child. The main cause is malacia or
benign stenosis. Management alternatives range from conservative treatment to
complex surgical and/or endoscopic techniques. Placement of a stent can play a
key role in situations where there is no other therapeutic option. However, the
ideal stent is not yet available. In the last few years, progress has been made
in the development and characterization of novel biodegradable materials in order
to overcome the drawbacks of traditional stents made of silicone or metal. We
present our experience with a new type of biodegradable airway stent in the
treatment of severe bronchomalacia in a 2-year-old child; we evaluate safety and
clinical effectiveness. We describe the indications and potential complications
of pediatric endoprosthesis in the airway.
PMID- 29333838
TI - Solitary median maxillary central incisor, holoprosencephaly and congenital nasal
pyriform aperture stenosis in a premature infant: case report.
AB - Solitary median maxillary central incisor syndrome is a rare disorder involving
midline abnormalities such as holoprosencephaly, nasal cavity anomalies, cleft
palate-lip, hypotelorism, microcephaly, and panhypopituitarism. Congenital nasal
pyriform aperture stenosis is a lethal cause of neonatal respiratory distress due
to narrowing of the pyriform aperture anteriorly and it can be confused with
choanal atresia. In this report, we present a newborn infant with solitary median
maxillary central incisor syndrome accompanied by other abnormalities including
holoprosencephaly, nasal pyriform aperture stenosis, microcephaly and
panhypopituitarism. Chromosomal analysis showed heterozygous SIX3 gene deletion
at 2p21 region resulting in a more severe form of holoprosencephaly.
PMID- 29333839
TI - [Pallister-Killian syndrome in a Mexican mestizo patient. Case report].
AB - Pallister-Killian syndrome is caused by a tetrasomy 12p mosaicism and is
characterized by facial dysmorphism, pigmentary skin anomalies, congenital heart
defects, diaphragmatic hernia, epilepsy and mental retardation. The diagnosis is
complex as the cytogenetic analysis in blood is usually normal, requiring
karyotyping in other tissues, therefore the clinical suspicion is critical to
guide the diagnostic tests and the patient requires an interdisciplinary clinical
evaluation regarding the several manifestation of the syndrome. W e present the
case of a Mexican mestizo female patient of 4 years of age referred by
psychomotor delay and cleft palate; the clinical multidisciplinary evaluation
demonstrated characteristics corresponding to the Pallister-Killian syndrome. The
GTG banding karyotype analysis was normal, the skin fibroblast was
mos47,XX,i(12)(p10)[85]/46,XX[21]. This case is an example of the importance of
the clinical evaluation in order to establish a diagnosis that is a challenge for
the clinical multidisciplinary team to offer medical management and genetic
counseling.
PMID- 29333840
TI - [Giant retroperitoneal lipoblastoma. Case report].
AB - Lipoblastoma is part of tumors derived from adipose tissue. It is a benign
neoplasm that can be localized or diffuse, affecting children in early childhood
and usually located in the trunk and extremities. These tumors are uncommon in
the pediatric age, but when one of them is present, it is a challenge that we
must resolve quickly due to the risk of malignancy that involves other similar
neoplastic lesions. The preoperative diagnosis is difficult, because the imaging
methods do not provide specific information that allows us to differentiate them
from other tumors, such as liposarcomas. The definitive diagnosis is
anatomopathological and, in doubtful cases, cytogenetic confirmation is
necessary. We present the case of a 14-month-old boy with diagnosis of large
sized lipoblastoma of retroperitoneal localization.
PMID- 29333841
TI - [Granular cell tumor of the larynx in the child. Case report].
AB - Laryngeal tumors are uncommon in children, accounting only for 2% of the
laryngeal anomalies. Ninety-eight percent are benign; the most frequent ones are
recurrent respiratory papillomatosis and haemangioma. Granular cell tumor, also
called Abrikossoff tumor, is an unusual benign neoplasm, especially in the
larynx. Clinical manifestations depend on the size and location of the tumor.
Dysphonia is the main presenting symptom. The diagnosis is confirmed by the
biopsy. The treatment of choice is surgery. We present a 9-year-old girl with
dysphonia and exertion dyspnea due to a granular cell tumor of the larynx, and we
emphasize the importance of considering the endoscopic evaluation of the airway
in every child with progressive or persistent dysphonia in order to determine the
etiology.
PMID- 29333842
TI - An adolescent with idiopathic pleuroparenchymal fibroelastosis. Case report.
AB - Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare disorder recently
included in rare idiopathic interstitial pneumonias according to the updated
American Thoracic Society/European Respiratory Society classification. IPPFE is
characterized by pleural and subpleural parenchymal fibrosis causing volume loss
predominantly in the upper lung lobes. Age of onset is variable, IPPFE mainly
occurs in third and fourth decades. We present a 16 year old patient with a 2
year history of exertional dyspnea, nonproductive cough and weight loss. On
physical examination, auscultation revealed diminished breath sounds on the upper
lobes. Chest radiograph showed apical pleural thickening and volume loss.
Computerized tomographic scan (CT) of chest revealed ground glass densities and
tubular bronchiectasis predominantly in upper lobes bilaterally, with
interlobular septal thickening of the pleura and enlarged mediastinal lymph
nodes. Thoracoscopic lung biopsy was performed and histological evaluation showed
subpleural fibrosis and elastic staining demonstrated fragmented elastic fiber
deposition in the subpleural area and adjacent pulmonary parenchyma suggesting
IPPFE. To our knowledge this is the first case in childhood. Therefore,
pediatricians should be aware of this disease for the diagnosis and appropriate
management.
PMID- 29333843
TI - [Use of the identification bracelet in the newborn. A safe method?]
AB - BACKGROUND: The placement of newborn bracelets is the most widely used method for
patient identification in Argentina. OBJECTIVES: To evaluate the permanence of
the identification bracelets during the hospitalization. POPULATION: All the term
newborns who remained with their mother. Design: observational, prospective
study, cohort type, randomized: forearm, leg. RESULTS: Cases observed: 914.
Forearm: 457, leg: 438. At the time of discharge, the frequency of permanence of
the identification bracelets as originally placed was 67% in the forearm and 72%
in the leg. CONCLUSIONS: A third of newborns lacked the bracelet as originally
placed at the time of discharge. The permanence was higher in the leg.
PMID- 29333844
TI - [Success in probing for congenital nasolacrimal duct obstruction. Ten years
experience].
AB - INTRODUCTION: The congenital nasolacrimal duct obstruction is a common pathology,
with low morbidity, but not exempt of complications without the correct diagnosis
and management. METHODS: Retrospective study from 2005 to 2015 in patients who
were submitted to a probing procedure. We identified age at procedure, gender,
laterality and presence or absence of success with the procedure. RESULTS: One
hundred thirty-seven eyes were analyzed. The median age was 17 months and the
total success rate was 85.4%. CONCLUSION: In congenital nasolacrimal duct
obstruction there is a high rate of spontaneous resolution with the proper
initial conservative management and, in patients older than 12 months, probing
has a high rate of success.
PMID- 29333845
TI - [Script Concordance Test: first nationwide experience in pediatrics].
AB - The Script Concordance Test is a suitable test for assessing clinical reasoning
in postgraduate medical education. We present the first nationwide, realtime, web
based experience of a Script Concordance Test administered to 3rd year pediatric
residents. The test was administered to 268 residents (postgraduate year 3), from
56 different programs, requiring 46.1 +/- 27.1 minutes to complete it, and
scoring 65.3 +/- 7.47 points. A later survey showed limited satisfaction from
participants. This experience showed that this kind of test is feasible in this
setting.
PMID- 29333846
TI - [Food allergy in children: recommendations for diagnosis and treatment].
AB - Food allergy arises from a specific immune response induced by food exposure. It
is the first cause of anaphylaxis in childhood. Its prevalence increased
exponentially in western countries. The proteins most frequently involved in
infants are cow's milk and hen's egg; and in adults, seafood. Peanuts have the
same frequency in both groups. The clinical manifestations and methodology of
study are directly related to the pathophysiology of the disease. Clinical
history, skin prick test, patch test, and food oral challenge are essential to
arrive at a correct diagnosis, that will avoid unnecessary exclusions or
exposures that carry life risk. The treatment is based on the correct avoidance
of responsible food (considering hidden allergens), besides patient and their
care giver's education, to maintain a good quality of life.
PMID- 29333847
TI - A Rare Cause of Acute Pancreatitis: Gastrostomy Catheter Migration.
PMID- 29333848
TI - Highly Stable and Luminescent Perovskite-Polymer Composites from a Convenient and
Universal Strategy.
AB - Extensive attention has been received in recent years for perovskite-polymer
composites because of their combination of properties from polymers and
perovskites. In this work, a convenient and universal strategy is reported to
prepare cesium lead bromide or organolead halide methylammonium bromide polymer
composites. This technique integrates the formation of perovskite crystals and
the polymer matrix in a one-pot reaction, avoiding the tedious separation and
preparation of perovskites. The method is universal for most of the commercially
available monomers and polymers, which has been verified in this report using
poly(methyl methacrylate), poly(butyl methacrylate), and polystyrene. The
physical properties of the varied polymers lead to different luminescent
properties and stabilities of the composites. No organic solvent is required
during the preparation, indicating a green technique for the composites.
Additionally, the resulted perovskite-polymer composites are extraordinarily
stable, maintaining their quantum yield for more than 1 month in air. On the
basis of the above properties, a prototype of white light-emitting diodes was
successfully constructed with feasible color characters and narrow bandwidths.
Furthermore, large-area (dimension: 10 * 7 * 0.15 cm) perovskite-polymer plates
are easily prepared via the one-pot strategy, showing that the technique is ready
for possible large-area optical devices. This work provides an efficient
technique toward various kinds of perovskite-polymer composites for both
scientific research studies and future applications.
PMID- 29333849
TI - Asymmetric Conjugate Addition of alpha-Cyanoketones to Enones Using
Diaminomethylenemalononitrile Organocatalyst.
AB - A diaminomethylenemalononitrile organocatalyst efficiently catalyzed the
asymmetric conjugate addition of alpha-cyanoketones to vinyl ketones to give the
corresponding 1,5-dicarbonyl compounds, which bear an all-carbon quaternary
stereogenic center with high enantioselectivities. This report is the first
example of the asymmetric conjugate addition of alpha-cyanoketones to vinyl
ketones using an organocatalyst.
PMID- 29333850
TI - Engineering NiS/Ni2P Heterostructures for Efficient Electrocatalytic Water
Splitting.
AB - Developing high-active and low-cost bifunctional materials for catalyzing the
hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) holds a
pivotal role in water splitting. Therefore, we present a new strategy to form
NiS/Ni2P heterostructures. The as-obtained NiS/Ni2P/carbon cloth (CC) requires
overpotentials of 111 mV for the HER and 265 mV for the OER to reach a current
density of 20 mA cm-2, outperforming their counterparts such as NiS and Ni2P
under the same conditions. Additionally, the NiS/Ni2P/CC electrode requires a
1.67 V cell voltage to deliver 10 mA cm-2 in a two-electrode electrolysis system,
which is comparable to the cell using the benchmark Pt/C||RuO2 electrode.
Detailed characterizations reveal that strong electronic interactions between NiS
and Ni2P, abundant active sites, and smaller charge-transfer resistance
contribute to the improved HER and OER activity.
PMID- 29333852
TI - Synthesis of Molecularly Imprinted Polymer Nanoparticles for alpha-Casein
Detection Using Surface Plasmon Resonance as a Milk Allergen Sensor.
AB - Food recalls due to undeclared allergens or contamination are costly to the food
manufacturing industry worldwide. As the industry strives for better
manufacturing efficiencies over a diverse range of food products, there is a need
for the development of new analytical techniques to improve monitoring of the
presence of unintended food allergens during the food manufacturing process. In
particular, the monitoring of wash samples from cleaning in place systems (CIP),
used in the cleaning of food processing equipment, would allow for the effective
removal of allergen containing ingredients in between food batches. Casein
proteins constitute the biggest group of proteins in milk and hence are the most
common milk protein allergen in food ingredients. As such, these proteins could
present an ideal analyte for cleaning validation. In this work, molecularly
imprinted polymer nanoparticles (nanoMIPs) with high affinity toward bovine alpha
casein were synthesized using a solid-phase imprinting method. The nanoMIPs were
then characterized and incorporated into label free surface plasmon resonance
(SPR) based sensor. The nanoMIPs demonstrated good binding affinity and
selectivity toward alpha-casein (KD ~ 10 * 10-9 M). This simple affinity sensor
demonstrated the quantitative detection of alpha-casein achieving a detection
limit of 127 +/- 97.6 ng mL-1 (0.127 ppm) which is far superior to existing
commercially available ELISA kits. Recoveries from spiked CIP wastewater samples
were within the acceptable range (87-120%). The reported sensor could allow food
manufacturers to adequately monitor and manage food allergen risk in food
processing environments while ensuring that the food produced is safe for the
consumer.
PMID- 29333851
TI - Oxygen Vacancy Dynamics at Room Temperature in Oxide Heterostructures.
AB - Oxygen vacancy dynamic behavior at room temperature in complex oxides was
carefully explored by using a combined approach of ion liquid gating technique
and resistance measurements. Heterostructures of PrBaCo2O5+delta/Gd2O3-doped CeO2
epitaxial thin films were fabricated on (001) Y2O3-stabilized ZrO2 single crystal
substrates for systematically investigating the oxygen redox dynamics. The oxygen
dynamic changes as response to the gating voltage and duration were precisely
detected by in situ resistance measurements. A reversible and nonvolatile
resistive switching dynamics was detected at room temperature under the gating
voltage >13.5 V with pulse duration >1 s.
PMID- 29333853
TI - Highly Sensitive and Very Stretchable Strain Sensor Based on a Rubbery
Semiconductor.
AB - There is a growing interest in developing stretchable strain sensors to quantify
the large mechanical deformation and strain associated with the activities for a
wide range of species, such as humans, machines, and robots. Here, we report a
novel stretchable strain sensor entirely in a rubber format by using a solution
processed rubbery semiconductor as the sensing material to achieve high
sensitivity, large mechanical strain tolerance, and hysteresis-less and highly
linear responses. Specifically, the rubbery semiconductor exploits pi-pi stacked
poly(3-hexylthiophene-2,5-diyl) nanofibrils (P3HT-NFs) percolated in silicone
elastomer of poly(dimethylsiloxane) to yield semiconducting nanocomposite with a
large mechanical stretchability, although P3HT is a well-known nonstretchable
semiconductor. The fabricated strain sensors exhibit reliable and reversible
sensing capability, high gauge factor (gauge factor = 32), high linearity (R2 >
0.996), and low hysteresis (degree of hysteresis <12%) responses at the
mechanical strain of up to 100%. A strain sensor in this format can be scalably
manufactured and implemented as wearable smart gloves. Systematic investigations
in the materials design and synthesis, sensor fabrication and characterization,
and mechanical analysis reveal the key fundamental and application aspects of the
highly sensitive and very stretchable strain sensors entirely from rubbers.
PMID- 29333854
TI - Cucurbit[8]uril-Based Giant Supramolecular Vesicles: Highly Stable, Versatile
Carriers for Photoresponsive and Targeted Drug Delivery.
AB - Highly stable giant supramolecular vesicles were constructed by hierarchical self
assembly of cucurbit[8]uril (CB[8])-based supra-amphiphiles for photoresponsive
and targeted intracellular drug delivery. These smart vesicles can encapsulate
the model drugs with high loading efficiencies and then release them by
manipulating photoswitchable CB[8] heteroternary complexation to regulate the
formation and dissociation of supra-amphiphiles that cause dramatic morphological
changes of the assemblies to achieve remote optically controlled drug delivery.
More importantly, the confocal microscopy analysis, cellular uptake experiment,
and cell viability assay have shown that the giant vesicles are able to maintain
the structural integrity and stability within actual cellular environments and
exhibit obvious advantages for intracellular drug delivery such as low toxicity,
easy surface modification for tumor-targeting selectivity, and rapid
internalization into different human cancer cell lines. A synergistic mechanism
that integrates multiple pathways including energy-dependent endocytosis,
macropinocytosis, cholesterol-dependent endocytosis, and microtubule-related
endocytosis was determined to facilitate the internalization process. Moreover,
cytotoxicity experiments and flow cytometric analysis have demonstrated that the
doxorubicin hydrochloride-loaded vesicles exhibited a significant therapeutic
effect for tumor cells upon UV light irradiation, which makes the photoresponsive
system more promising for potential applications in pharmaceutically relevant
fields.
PMID- 29333855
TI - Carbon- and Binder-Free Core-Shell Nanowire Arrays for Efficient Ethanol Electro
Oxidation in Alkaline Medium.
AB - To achieve high electrochemical surface area (ECSA) and avoid carbon support and
binder in the anode catalyst of direct ethanol fuel cell, herein, we design
freestanding core-shell nickel@palladium-nickel nanowire arrays (Ni@Pd-Ni NAs)
without carbon support and binder for high-efficiency ethanol electro-oxidation.
Bare Ni nanowire arrays (Ni NAs) are first prepared using the facile template
assistant electrodeposition method. Subsequently, the Ni@Pd-Ni NAs are formed
using one-step solution-based alloying reaction. The optimized Ni@Pd-Ni NA
electrode with a high ECSA of 64.4 m2 g-1Pd exhibits excellent electrochemical
performance (peak current density: 622 A g-1Pd) and cycling stability for ethanol
electro-oxidation. The facilely obtained yet high-efficiency core-shell Ni@Pd-Ni
NA electrode is a promising electrocatalyst, which can be utilized for oxygen
reduction reaction, urea, hydrazine hydrate, and hydrogen peroxide electro
oxidation, not limited to the ethanol electro-oxidation.
PMID- 29333856
TI - Analysis of the pH-Dependent Fe(III) Ion Chelating Activity of Anthocyanin
Extracted from Black Soybean [Glycine max (L.) Merr.] Coats.
AB - The Fe(III) chelating activity of anthocyanin extracted from black soybean coats
was investigated at pH 3.0, 5.0, 6.5, 7.0, and 7.4 with fluorescence spectroscopy
and microscale thermophoresis (MST). Cyanidin-3-glucoside (C3G) was determined to
be 98% of the total anthocyanin by high-performance liquid chromatography. The
binding affinity (Ka) exhibited significant pH-dependent behavior: Ka was 9.7167
* 104, 1.0837 * 104, 1.4284 * 104, 5.4550 * 104, and 3.0269 * 104 M-1 at pH 3.0,
5.0, 6.5, 7.0, and 7.4, respectively (p < 0.05). The MST data showed that DeltaG
< 0 and DeltaH < 0, demonstrating that chelation is spontaneous and exothermic.
Because both DeltaH and DeltaS < 0, the chelation involves hydrogen bonds and/or
van der Waals forces for pH 3.0, 5.0, and 6.5. Electrostatic interactions
contributed to chelation at pH 7.0 and 7.4 with DeltaH < 0 and DeltaS > 0. With
the formation of chelates, C3G improved the solubility of Fe(III) at pH 6.5, 7.0,
and 7.4 to enhance the ferric ion bioavailability, except for aggregation
observed at pH 5.0.
PMID- 29333857
TI - Active Site Revealed for Water Oxidation on Electrochemically Induced delta-MnO2:
Role of Spinel-to-Layer Phase Transition.
AB - Seeking for active MnOx material as artificial water splitting catalyst has been
a long history since the discovery of PSII system in nature. To date, the highest
activity MnOx catalyst reported for oxygen evolution reaction (OER) does however
not belong to common MnO2 polymorphs (alpha-, beta-, delta-MnO2), but rather to
nascent delta-MnO2 layer produced in situ from spinel under electrochemical
conditions with unknown active site structure. Here with the stochastic surface
walking (SSW) pathway sampling method, we for the first time resolve the atomic
level mechanism of spinel-to-layer Mn3O4 solid phase transition in aqueous
electrolyte. We show that a transient H0.5MnO2 phase is the precursor of
transition that forms at high voltage (>1 V), and it undergoes the solid-to-solid
phase transition to produce a delta-MnO2 layer, which is accompanied by Mn
dissolution, dislocation, layer-breaking, and insertion of water/cations between
layers. This leads to the generation of a variety of possible defective
structures. We demonstrate using first-principles calculations that a special
edge site with neighboring Mn vacancy provides the best OER activity with an
overpotential of 0.59 V, 0.19 V lower than that of pristine MnO2. The high
activity of such Mn sites are attributed to its special local structure:
pseudocubane with one corner missing. The presence of the Mn vacancy near the
active site enhances the adsorption of OH intermediate in OER. This defective
cubane structure shares the common geometrical and electronic features found in
the PSII system.
PMID- 29333858
TI - Mineral- and Base-Catalyzed Hydrolysis of Organophosphate Flame Retardants:
Potential Major Fate-Controlling Sink in Soil and Aquatic Environments.
AB - The ubiquitous occurrence of organophosphate flame retardants (OPFRs) in aquatic
and soil environments poses significant risks to human health and ecosystems.
Here, we report on the hydrolysis of six OPFRs and three structural analogues in
the absence and presence of metal (hydr)oxide minerals. Eight of the target
compounds showed marked degradation in alkaline solutions (pH 9-12) with half
lives ranging from 0.02-170 days. Kinetics follow a second-order rate law with
apparent rate constants for base-catalyzed hydrolysis (kB) ranging from 0.69-42
000 M-1 d-1. Although hydrolysis in homogeneous solution at circumneutral pH is
exceedingly slow (t1/2 > 2 years, except for tris(2,2,2-trichloroethy)
phosphate), rapid degradation is observed in the presence of metal (hydr)oxide
minerals, with half-lives reduced to <10 days for most of the target OPFRs in
mineral suspensions (15 m2/L mineral surface area loading). LC-qToF-MS analysis
of transformation products confirmed ester hydrolysis as the active degradation
pathway. Values of kB for individual OPFRs are highly variable and correlate with
acid dissociation constants (pKa) of the corresponding alcohol leaving groups. In
contrast, kinetic parameters for mineral-catalyzed reactions are much less
sensitive to OPFR structure, indicating that other factors like mineral-OPFR
interactions are rate controlling. Given the documented recalcitrance of OPFRs to
biodegradation and photodegradation, these results suggest that mineral-catalyzed
hydrolysis may be a major fate-controlling sink in natural environments.
PMID- 29333859
TI - Chromatographic Separation and Visual Detection on Wicking Microfluidic Devices:
Quantitation of Cu2+ in Surface, Ground, and Drinking Water.
AB - Copper is widely applied in industrial and technological applications and is an
essential micronutrient for humans and animals. However, exposure to high
environmental levels of copper, especially through drinking water, can lead to
copper toxicity, resulting in severe acute and chronic health effects. Therefore,
regular monitoring of aqueous copper ions has become necessary as recent
anthropogenic activities have led to elevated environmental concentrations of
copper. On-site monitoring processes require an inexpensive, simple, and portable
analytical approach capable of generating reliable qualitative and quantitative
data efficiently. Membrane-based lateral flow microfluidic devices are ideal
candidates as they facilitate rapid, inexpensive, and portable measurements. Here
we present a simple, chromatographic separation approach in combination with a
visual detection method for Cu2+ quantitation, performed in a lateral flow
microfluidic channel. This method appreciably minimizes interferences by
incorporating a nonspecific polymer inclusion membrane (PIM) based assay with a
"dot-counting" approach to quantification. In this study, hydrophobic
polycaprolactone (PCL)-filled glass microfiber (GMF) membranes were used as the
base substrate onto which the PIM was evenly dispensed as an array of dots. The
devices thus prepared were then selectively exposed to oxygen radicals through a
mask to generate a hydrophilic surface path along which the sample was wicked.
Using this approach, copper concentrations from 1 to 20 ppm were quantified from
5 MUL samples using only visual observation of the assay device.
PMID- 29333860
TI - Copper(II)-Mediated ortho-Selective C(sp2)-H Tandem Alkynylation/Annulation and
ortho-Hydroxylation of Anilides with 2-Aminophenyl-1H-pyrazole as a Directing
Group.
AB - 2-Aminophenyl-1H-pyrazole has been identified as a viable directing group to
promote copper(II)-mediated ortho-selective sp2 C-H bond tandem
alkynylation/annulation of anilides with terminal alkynes to offer arylmethylene
isoindolinones. Meanwhile, copper(II)-mediated ortho-selective sp2 C-H
hydroxylation of anilides has also been optimized as the major reaction pathway
by using Cu(OAc)2 as the promoter and 1,1,3,3-tetramethylguanidine as an organic
base. Recovery of the directing group was achieved by hydrazinolysis for
arylmethylene isoindolinones and basic hydrolysis for the hydroxylation products.
PMID- 29333861
TI - Intra- and inter-observer agreement in the visual interpretation of interim 18F
FDG PET/CT in malignant lymphoma: influence of clinical information.
AB - Background Interim PET/CT is widely performed in lymphoma patients in clinical
practice and clinical trials. Visual assessment using a 5-point scale is proposed
for PET/CT interpretation, but intra- and inter-observer variation is not fully
investigated. Purpose To investigate intra- and inter-observer variations in the
reporting of interim positron emission tomography/computed tomography (PET/CT) in
lymphoma patients, and the influence of clinical information on the
interpretation. Material and Methods Three expert readers from different
institutions interpreted interim PET/CT images of 42 consecutive patients with
malignant lymphoma twice, with and without clinical information. The intra- and
inter-observer agreements were calculated using the kappa statistic on a patient
and a region basis. Results On a patient basis, intra-observer agreement, inter
observer agreement without information, and inter-observer agreement with
information were within the ranges 0.48-0.62, 0.51-0.62, and 0.42-0.76,
respectively. In the evaluation of lymph nodes, intra-observer agreement, inter
observer agreement without information, and inter-observer agreement with
information were within the ranges 0.78-0.92, 0.80-0.82, and 0.77-0.83,
respectively. Observer agreements were in almost perfect to substantial agreement
categories for most lymphatic organs, but were generally low for the other
organs. Conclusion The intra- and inter-observer agreements in evaluating interim
PET/CT were relatively low for extranodal lesions, but they were substantial to
almost perfect when interpreting nodal regions in malignant lymphoma,
irrespective of the provision of clinical information, although memory at the
first interpretation might have affected the intra-observer results.
PMID- 29333862
TI - Pharmacokinetic determination and analysis of nortriptyline based on GC-MS
coupled with hollow-fiber drop-to-drop solvent microextraction technique.
AB - AIM: A simple, sensitive and robust technique of hollow-fiber drop-to-drop
solvent microextraction coupled with GC-MS has been successfully developed for
the detection of antidepressant drug nortriptyline in human blood and urine
samples. The recoveries of the drug from the spiked samples are found to be well
within the range and appropriate to support the method. RESULTS: The LOD for the
drug was obtained to be 0.007, 0.009 and 0.021 MUg ml-1 in deionized water, urine
and blood samples of human subjects, respectively. Linearity was obtained over
the concentration range of 0.5-5.0 mg l-1 in deionized water with correlation
coefficient 0.99672.
PMID- 29333863
TI - Principles of vaccine potency assays.
AB - Compared with biologics, vaccine potency assays represent a special challenge due
to their unique compositions, multivalency, long life cycles and global
distribution. Historically, vaccines were released using in vivo potency assays
requiring immunization of dozens of animals. Modern vaccines use a variety of
newer analytical tools including biochemical, cell-based and immunochemical
methods to measure potency. The choice of analytics largely depends on the
mechanism of action and ability to ensure lot-to-lot consistency. Live vaccines
often require cell-based assays to ensure infectivity, whereas recombinant
vaccine potency can be reliably monitored with immunoassays. Several case studies
are presented to demonstrate the relationship between mechanism of action and
potency assay. A high-level decision tree is presented to assist with assay
selection.
PMID- 29333864
TI - Non-digestible carbohydrates in infant formula as substitution for human milk
oligosaccharide functions: Effects on microbiota and gut maturation.
AB - Human milk (HM) is the golden standard for nutrition of newborn infants. Human
milk oligosaccharides (HMOs) are abundantly present in HM and exert multiple
beneficial functions, such as support of colonization of the gut microbiota,
reduction of pathogenic infections and support of immune development. HMO
composition is during lactation continuously adapted by the mother to accommodate
the needs of the neonate. Unfortunately, for many valid reasons not all neonates
can be fed with HM and are either totally or partly fed with cow-milk derived
infant formulas, which do not contain HMOs. These cow-milk formulas are
supplemented with non-digestible carbohydrates (NDCs) that have functional
effects similar to that of some HMOs, since production of synthetic HMOs is
challenging and still very expensive. However, NDCs cannot substitute all HMO
functions. More efficacious NDCs may be developed and customized for specific
groups of neonates such as pre-matures and allergy prone infants. Here current
knowledge of HMO functions in the neonate in view of possible replacement of HMOs
by NDCs in infant formulas is reviewed. Furthermore, methods to expedite
identification of suitable NDCs and structure/function relationships are reviewed
as in vivo studies in babies are impossible.
PMID- 29333865
TI - Parental supervision and discomfort with children walking to school in low-income
communities in Cape Town, South Africa.
AB - OBJECTIVE: The risk of pedestrian injury is compounded for children living in low
income communities due to factors such as poor road and pedestrian
infrastructure, reliance on walking as a means of transport, and compromised
supervision. Parents play an important role in child pedestrian safety. The
primary objective of this study was to examine the effects of child pedestrian
variables on parental discomfort with regard to letting their child walk to and
from school and on the frequency of adult supervision. METHODS: A cross-sectional
study was conducted using a convenience sample from 3 schools participating in a
pedestrian safety school initiative. The schools are situated in low-income, high
risk communities in the City of Cape Town. A parent survey form was translated
into isiXhosa and sent home with learners to those parents who had consented to
participate. The response rate was 70.4%, and only parents of children who walk
to and from school were included in the final sample (n = 359). Child pedestrian
variables include the time taken to walk to school, parental rating of the
child's ability to safely cross the road, and the frequency of adult supervision.
RESULTS: More than half of parents reported that their child walked to and from
school without adult supervision. About 56% of children took less than 20 min to
walk to school. Most parents (61%) were uncomfortable with their child walking to
school, although the majority of parents (55.7%) rated their child's ability to
cross the road safely as better or significantly better than average (compared to
peers). The parents did not perceive any differences in pedestrian risk factors
between boys and girls or between younger (6-9 years) and older (10-15 years)
children. The time spent by a child walking to school and parents' perceptions of
their child's road-crossing ability were found to be significant predictors of
parental discomfort (in letting their child walk). Younger children and children
who spent less time walking were more likely to be supervised by an adult.
CONCLUSIONS: Many South African schoolchildren have to navigate the roads without
adult supervision from a young age. Caregivers, especially in low-income
settings, often have limited options with regard to getting their child to school
safely. Regardless of the child's age and gender, the time that they spend on the
roads is an important factor for parents in terms of pedestrian safety.
PMID- 29333867
TI - What is the meaning of filial piety for people with dementia and their family
caregivers in China under the current social transitions? An interpretative
phenomenological analysis.
AB - The filial piety model of family centred care has dominated Chinese society for
thousands of years. The ways in which filial piety is presented are being
modified and modernised as China undergoes social transitions. The study aims to
understand the meaning of filial piety for people with dementia and family
caregivers. Semi-structured interviews with people with dementia ( n = 10) and
family caregivers ( n = 14) were conducted. Data were analysed using
interpretative phenomenological analysis. Three themes emerged: (a) 'Being filial
is a cultural continuity and my future investment'. (b) 'The changed perception
and ways of being filial'. (c) 'Filial responsibility is a social and cultural
convention, but not my personal choice'. This study highlights the importance of
cultural values in family care decision making and in shaping filial
responsibilities. It indicates that filial obligation can be maintained through
social support, even though the nature of filial piety has been changed by social
transitions.
PMID- 29333866
TI - Offline derivatization LC-MS/MS method for simultaneous estimation of vanillin
and vanillic acid in guinea pig plasma.
AB - AIM: Vanillin used as a positive control substrate of aldehyde oxidase activity
gets metabolized to vanillic acid. Low MW and low sensitivity in negative ion
mode are challenges with these analytes. Our objective was to develop a simple
offline derivatization LC-MS/MS method to address these challenges.
METHODOLOGY/RESULTS: A simple dansyl chloride derivatization of the phenolic
groups on vanillin and vanillic acid was adopted to enable easy ionization in
commonly used acidic mobile phases. Calibration curves were linear over the
concentrations of 4.88-1250 nM with an LLOQ of 0.64 fmoles on column for both
analytes. CONCLUSION: The qualified method was successfully applied to
simultaneously measure vanillin and vanillic acid in plasma and urine from a
guinea pig pharmacokinetic study.
PMID- 29333868
TI - Drug detection in biological specimens: recent colorimetric methods.
PMID- 29333869
TI - Quantitation of saxitoxin in human urine using immunocapture extraction and LC
MS.
AB - AIM: An immunomagnetic capture protocol for use with LC-MS was developed for the
quantitation of saxitoxin (STX) in human urine. MATERIALS & METHODS: This method
uses monoclonal antibodies coupled to magnetic beads. STX was certified reference
material grade from National Research Council, Canada. Analysis was carried out
using LC-MS. RESULTS: With an extraction efficiency of 80%, accuracy and
precision of 93.0-100.2% and 5.3-12.6%, respectively, and a dynamic range of 1.00
100 ng/ml, the method is well suited to quantify STX exposures based on
previously reported cases. CONCLUSION: Compared with our previously published
protocols, this method has improved selectivity, a fivefold increase in
sensitivity and uses only a third of the sample volume. This method can diagnose
future toxin exposures and may complement the shellfish monitoring programs
worldwide.
PMID- 29333870
TI - The effects of aerobic exercise for persons with migraine and co-existing tension
type headache and neck pain. A randomized, controlled, clinical trial.
AB - Aim To evaluate aerobic exercise in migraine and co-existing tension-type
headache and neck pain. Methods Consecutively recruited persons with migraine and
co-existing tension-type headache and neck pain were randomized into an exercise
group or control group. Aerobic exercise consisted of bike/cross-trainer/brisk
walking for 45 minutes, three times/week. Controls continued usual daily
activities. Pain frequency, intensity, and duration; physical fitness, level of
physical activity, well-being and ability to engage in daily activities were
assessed at baseline, after treatment and at follow-up. Results Fifty-two persons
completed the study. Significant between-group improvements for the exercise
group were found for physical fitness, level of physical activity, migraine
burden and the ability to engage in physical activity because of reduced impact
of tension-type headache and neck pain. Within the exercise group, significant
reduction was found for migraine frequency, pain intensity and duration, neck
pain intensity, and burden of migraine; an increase in physical fitness and well
being. Conclusions Exercise significantly reduced the burden of migraine and the
ability to engage in physical activity because of reduced impact of tension-type
headache and neck pain. Exercise also reduced migraine frequency, pain intensity
and duration, although this was not significant compared to controls. These
results emphasize the importance of regular aerobic exercise for reduction of
migraine burden.
PMID- 29333871
TI - Drug monitoring by volumetric absorptive microsampling: method development
considerations to mitigate hematocrit effects.
AB - AIM: GSKA is a compound that was in development in clinical trials. A bioanalysis
method to quantify GSKA using volumetric absorptive microsampling (VAMS) was
developed and hematocrit (HCT) related assay bias was investigated. METHODOLOGY:
After accurate sampling of 10 MUl blood, VAMS tips were air dried approximately
18 h and desorbed by an aqueous solution containing internal standard. The
recovered blood underwent liquid-liquid extraction in ethyl acetate to minimize
matrix suppression. Assay accuracy, precision, linearity, carryover, selectivity,
recovery, matrix effects, HCT effects and long-term quality control stability
were evaluated. CONCLUSION: HCT-related assay bias was minimized in 30-60% blood
HCT range, and all validation parameters met acceptance criteria. The method is
suitable for quantitative analysis of GSKA in human blood.
PMID- 29333872
TI - Effects and underlying mechanisms of unstable shoes on chronic low back pain: a
randomized controlled trial.
AB - OBJECTIVE: To investigate the effects that wearing unstable shoes has on
disability, trunk muscle activity, and lumbar spine range of motion (ROM) in
patients with chronic lower back pain (CLBP). DESIGN: Randomized controlled
trial. SETTING: Orthopedic Surgery Service. PARTICIPANTS: We randomized 40 adults
with nonspecific CLBP either to an unstable shoes group ( n = 20) or to the
control group ( n = 20). INTERVENTION: The participants in the unstable shoes
group were advised to wear these shoes for a minimum of six hours a day for four
weeks. Control group participants were asked to continue wearing their regular
shoes. OUTCOME MEASURES: Our primary outcome was measurement of back-related
dysfunction, assessed using the Roland-Morris Disability Questionnaire. Secondary
outcomes included changes in electromyographic (EMG) activity of erector spinae
(ES), rectus abdominis (RA), internus obliquus (IO), and externus obliquus (EO)
muscles, and changes in lumbar spine ROM. RESULTS: Between-group analysis
highlighted a significant decrease in disability in the unstable shoes group
compared to the control (-5, 95% confidence interval (CI) = -8.4 to -1.6). Our
results revealed a significant increase in the percentage of RA, ES, IO, and EO
EMG activity and in lumbar spine ROM in the unstable shoes group compared to the
control group. Moreover, our results showed a significant negative correlation
between disability and the percentage of ES, RA, and IO muscle activity at the
end of the intervention. CONCLUSION: This study shows that the use of unstable
shoes contributes to improvements in disability, which are likely related to
increased trunk muscle activity and lumbar spine ROM.
PMID- 29333873
TI - Survey regarding the 0.05 blood alcohol concentration limit for driving in the
United States.
AB - BACKGROUND: On May 14, 2013, the National Transportation Safety Board (NTSB)
proposed that states lower the blood alcohol concentration (BAC) illegal limit
from 0.08 to 0.05 g/dL (also referred to as the 0.08 law and the 0.05 limit,
respectively). In March 2017, this recommendation was signed into law in the
State of Utah. OBJECTIVE: The objective of this survey is to investigate
perceptions regarding enforcement of the 0.05 g/dL BAC limit. METHOD: Opinions of
law enforcement officers, prosecutors, and defense attorneys were obtained
through a series of questionnaires and focus groups. RESULTS: Survey data were
collected from 32 law enforcement officers, 20 prosecutors, and 4 defense
attorneys. The participants rated the usefulness of the NHTSA's driving while
intoxicated (DWI) driving cues lower for the 0.05 limit than for the 0.08 law.
Some of the participants believed that training would be needed in regard to
sobriety testing under the 0.05 limit. Participants also stated that adequately
preparing for prosecution of drunk drivers would be more difficult under the 0.05
limit. In addition, it was believed that drunk driving cases are more likely to
be withdrawn and fewer plea agreements and guilty pleas are likely under the 0.05
limit. Prosecutors were concerned that the 0.05 limit would result in poorly
investigated cases and overburden the court system. Defense attorneys were
concerned about the social and economic costs of a 0.05 limit. DISCUSSION:
Overall, it appears that the 0.05 limit is viewed as enforceable and it will save
lives; however, the usefulness of the NHTSA DWI Detection Guide and of the
standardized field sobriety tests need to be established for lower BACs, and
efforts must be made to educate people regarding the relationship between BAC and
impairment and impairment and driving with the risk of injury and death.
CONCLUSION: Though the 0.05 limit offers promise in saving lives, the following
issues associated with changing the limit to 0.05 need to be resolved prior to
implementation: Validating the sobriety tests for the 0.05 limit; if needed,
modifying the sobriety tests to make them effective and valid at the 0.05 limit;
and training law enforcement personnel and educating the public regarding the
0.05 limit.
PMID- 29333874
TI - Road traffic injuries among riders of electric bike/electric moped in southern
China.
AB - OBJECTIVE: Electric bike/moped-related road traffic injuries have become a
burgeoning public health problem in China. The objective of this study was to
identify the prevalence and potential risk factors of electric bike/moped-related
road traffic injuries among electric bike/moped riders in southern China.
METHODS: A cross-sectional study was used to interview 3,151 electric bike/moped
riders in southern China. Electric bike/moped-related road traffic injuries that
occurred from July 2014 to June 2015 were investigated. Data were collected by
face-to-face interviews and analyzed between July 2015 and June 2017. RESULTS:
The prevalence of electric bike/moped-related road traffic injuries among the
investigated riders was 15.99%. Electric bike/moped-related road traffic injuries
were significantly associated with category of electric bike (adjusted odds ratio
[AOR] = 1.36, 95% confidence interval [CI], 1.01-1.82), self-reported confusion
(AOR = 1.77, 95% CI, 1.13-2.78), history of crashes (AOR = 6.14, 95% CI, 4.68
8.07), running red lights (AOR = 3.57, 95% CI, 2.42-5.25), carrying children
while riding (AOR = 1.96, 95% CI, 1.37-2.85), carrying adults while riding (AOR =
1.68, 95% CI, 1.23-2.28), riding in the motor lane (AOR = 2.42, 95% CI, 1.05
3.93), and riding in the wrong traffic direction (AOR = 1.63, 95% CI, 1.13-2.35).
In over 77.58% of electric bike/moped-related road traffic crashes, riders were
determined by the police to be responsible for the crash. Major crash-causing
factors included violating traffic signals or signs, careless riding, speeding,
and riding in the wrong lane. CONCLUSION: Traffic safety related to electric
bikes/moped is becoming more problematic with growing popularity compared with
other 2-wheeled vehicles. Programs need to be developed to prevent electric
bike/moped-related road traffic injuries in this emerging country.
PMID- 29333876
TI - Figuring It Out: How Late Adolescent and Young Adult Men and Women Perceive and
Address Problems in Sexual Functioning.
AB - Although there are high rates of sexual problems and sexual dysfunction in
adulthood (Mitchell et al., 2013), little is known about the circumstances under
which problems are first experienced. A growing body of research addresses
prevalence of problems in sexual functioning among adolescents and young adults,
yet little is known about the meanings that young people give to these
experiences or how they deal with them. We used content analysis of qualitative
interviews with 53 heterosexual, sexually active Canadian adolescents (ages 18 to
21) to explore their perceptions of the sexual problems in functioning they had
experienced and the strategies (if any) they used to address them over time.
Problems among most young people originated early in their partnered sexual life.
Figuring it out emerged as an intentional process directed toward improving
sexual experiences, although certainly not all young people were successful.
Strategies for figuring it out included informational or material help seeking,
experimentation to inform future actions, mutual sharing and problem solving, and
building emotional connection to improve sexual functioning. Implications for
understanding the development of sexual dysfunctions in adulthood are discussed.
PMID- 29333875
TI - Ultrafast determination of vitamin E using LC-ESI-MS/MS for preclinical
development of new nutraceutical formulations.
AB - AIM: We proposed a rapid and high quality method to determine alpha-tocopherol
(alpha-T) in different biopharmaceutical samples using liquid chromatography
diode array detector on-line ESI-MS/MS. MATERIALS & METHODS: A working standard
solution of alpha-T and internal standard, phenyl-5,7-dimethyl-d6-alpha
tocopherol, were used for optimization and validation of the method. Levels of
alpha-T in nanoemulsions, serum and plasma samples were evaluated. RESULTS &
CONCLUSION: Precision (1% for retention time, 5% for peak area and 3% for
relative peak area), linearity range (among 0.625-20.0 MUg ml-1), LOD and LOQ,
accuracy and matrix effect were studied. The validated chromatographic method is
presented as valuable analytical tool for the determination of alpha-tocopherol
in loaded drug delivery systems and in biodistribution levels in blood samples.
PMID- 29333877
TI - What Behaviors Do Young Heterosexual Australians See in Pornography? A Cross
Sectional Study.
AB - This study investigated how frequently a group of young heterosexual Australians
(ages 15 to 29) saw a range of behaviors represented in pornography over the
previous 12 months. Participants were recruited to an anonymous online survey.
Those who reported having viewed pornography in the past 12 months (n = 517)
indicated how frequently they saw each of a list of 17 behaviors when they
watched pornography in the past 12 months. Men's pleasure (83%) was seen
frequently by the highest proportion of young people surveyed, followed by a man
being portrayed as dominant (70%). Women were more likely to report frequently
seeing violence toward a woman (p < 0.01). Men were more likely to report
frequently seeing heterosexual anal sex (p < 0.01), ejaculation onto a woman's
face (p < 0.01), women portrayed as dominant (p < 0.01), a man being called names
or slurs (p < 0.01), and violence toward a man that appears consensual (p <
0.01). Younger age was significantly associated with frequently seeing women's
pleasure (p < 0.05), violence toward women which appeared consensual, and all
types of violence (p < 0.01). Older age was associated with frequently seeing
men's pleasure (p < 0.01) and heterosexual anal sex (p < 0.05). Our findings draw
attention to the gendered ways that behaviors in pornography are seen and
identified by young heterosexual audiences.
PMID- 29333878
TI - Glucagon receptor signalling - backwards and forwards.
PMID- 29333879
TI - Negotiating the Interpretation of Depression Shared Among Kin.
AB - Kinship processes contribute to the experience and interpretation of depression
generating empathy as well as silencing. We explore intersubjective experiences
of depression among kin with the aim of understanding how depression can reveal
kinship expectations and evolving concepts of distress. In interviews with 28 low
income rural Appalachian women about their depression, participants articulated
depression as a social process that neither starts nor ends in themselves. Yet
kinship obligations to recognize family members' depression limited women's
ability to admit distress, let alone request care. The intersubjective experience
of depression among kin can challenge the individual expression of distress.
PMID- 29333881
TI - Reproductive Travel to Ghana: Testimonies, Transnational Relationships, and
Stratified Reproduction.
AB - In this article, I address reproductive travel to Ghana, based on research
conducted in two private fertility clinics. Both clinics attract clients from
West African countries as well as Ghanaian people living in the US and Europe.
Their motivations to visit these clinics include positive "testimonies" about
treatment results, "bioavailability" of matching donor material and surrogates,
lower treatment costs and the circumvention of restricting regulations in the
country of residence. Communication technologies are central in facilitating
reproductive travel. Finally, I argue that the "international choreographies" of
reproductive travel are co-shaped by the unique biographies and transnational
relationships of the people involved.
PMID- 29333882
TI - Vaginoplasty: What's New From 1946 to Date Commentary on: Vaginoplasty with
Acellular Dermal Matrix after Radical Resection for Carcinoma of the Uterine
Cervix.
PMID- 29333880
TI - Pharmacogenetic analysis of opioid dependence treatment dose and dropout rate.
AB - BACKGROUND: Currently, no pharmacogenetic tests for selecting an opioid
dependence pharmacotherapy have been approved by the US Food and Drug
Administration. OBJECTIVES: Determine the effects of variants in 11 genes on
dropout rate and dose in patients receiving methadone or buprenorphine/naloxone
(ClinicalTrials.gov Identifier: NCT00315341). METHODS: Variants in six
pharmacokinetic genes (CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4) and five
pharmacodynamic genes (HTR2A, OPRM1, ADRA2A, COMT, SLC6A4) were genotyped in
samples from a 24-week, randomized, open-label trial of methadone and
buprenorphine/naloxone for the treatment of opioid dependence (n = 764; 68.7%
male). Genotypes were then used to determine the metabolism phenotype for each
pharmacokinetic gene. Phenotypes or genotypes for each gene were analyzed for
association with dropout rate and mean dose. RESULTS: Genotype for 5-HTTLPR in
the SLC6A4 gene was nominally associated with dropout rate when the methadone and
buprenorphine/naloxone groups were combined. When the most significant variants
associated with dropout rate were analyzed using pairwise analyses, SLC6A4 (5
HTTLPR) and COMT (Val158Met; rs4860) had nominally significant associations with
dropout rate in methadone patients. None of the genes analyzed in the study was
associated with mean dose of methadone or buprenorphine/naloxone. CONCLUSIONS:
This study suggests that functional polymorphisms related to synaptic dopamine or
serotonin levels may predict dropout rates during methadone treatment. Patients
with the S/S genotype at 5-HTTLPR in SLC6A4 or the Val/Val genotype at Val158Met
in COMT may require additional treatment to improve their chances of completing
addiction treatment. Replication in other methadone patient populations will be
necessary to ensure the validity of these findings.
PMID- 29333883
TI - Simultaneous Intestinal and Kidney Transplantation in Adults.
AB - AIM OF THE STUDY: Intestinal transplantation (IT) is a life-saving procedure for
carefully selected patients with intestinal failure. We evaluated patients who
had undergone simultaneous intestinal and kidney transplantation (SIKT) to
determine whether UK guidelines for inclusion of a renal allograft (dialysis
dependent or estimated glomerular filtration rate ((eGFR)) < 45 ml/min/1.73 m2)
are justified. METHODS: A single centre analysis was undertaken of adults
undergoing IT at the Cambridge Transplant Centre between December 2007 and
January 2016. A prospectively maintained database was used to identify SIKT
recipients and determine outcomes. RESULTS: Over this period, 63 intestinal
transplants were performed. Seven (11.1%) recipients received a SIKT. Five were
pre-dialysis (median eGFR 29 ml/min/1.73 m2, range 16-36 ml/min/1.73 m2). One
recipient was on dialysis, and one needed bilateral nephrectomy at transplant.
There were no primary kidney allograft failures and at three months, the median
eGFR (55 ml/min/1.73 m2 range 39-124) was similar to recipients of IT alone
(median eGFR 56 ml/min/1.73 m2 range 17-143 ml/min/1.73 m2). Two recipients
required dialysis due to sepsis related kidney injury and died from multi-organ
failure (20 and 63 months). Two died with a functioning renal transplant (10 and
15 months). The remaining three patients are alive at follow up (12-96 months)
with an eGFR of 20-45 ml/min/1.73 m2. CONCLUSION: Patients with significant renal
impairment (eGFR <45 ml/min/1.73 m2), and receiving dialysis may benefit from
SIKT. Patient survival and renal function are broadly comparable to those
undergoing IT alone. Further studies are required to justify allocation of a
kidney to this complex high risk group.
PMID- 29333884
TI - Use of tidal breathing curves for evaluating expiratory airway obstruction in
infants.
AB - OBJECTIVE: To evaluate tidal breathing (TB) flow-volume and flow-time curves for
identification of expiratory airway obstruction in infants. METHODS: Pulmonary
function tests were analyzed retrospectively in 156 infants aged 3-24 months with
persistent or recurrent respiratory complaints. Parameters derived from TB curves
were compared to maximal expiratory flow at functional residual capacity
([Formula: see text]maxFRC) measured by rapid thoracoabdominal compression
technique. Analyzed parameters were: inspiratory time (tI), expiratory time (tE),
tidal volume, peak tidal expiratory flow (PTEF), time to peak tidal expiratory
flow (tPTEF), expiratory flow when 50% and 25% of tidal volume remains in the
lungs (FEF50, FEF25, respectively), and the ratios tPTEF/tE, tI/tE, FEF50/PTEF,
and FEF25/PTEF. Statistical comparisons between flow indices and TB parameters
were performed using mean squared error and Pearson's sample correlation
coefficient. The study population was also divided into two groups based on
severity of expiratory obstruction (above or below z-score for [Formula: see
text]maxFRC of -2) to generate receiver operating characteristic (ROC) curves and
calculate discriminatory values between the groups. RESULTS: TB parameters that
were best correlated to [Formula: see text]maxFRC were: tPTEF/tE, FEF50/PTEF, and
FEF25/PTEF, with r = 0.61, 0.67, 0.65, respectively (p < 0.0001 for all). ROC
curves for FEF50/PTEF, FEF25/PTEF and tPTEF/tE showed areas under the curve of
0.813, 0.797, and 0.796, respectively. Cutoff value z-scores of -0.35, -0.34, and
-0.43 for these three parameters, respectively, showed an 86% negative predictive
value for severe airway obstructions. CONCLUSION: TB curves can assist in ruling
out severe expiratory airway obstruction in infants.
PMID- 29333885
TI - When biomarkers define a drug indication.
PMID- 29333887
TI - Physical and Psychological Abuse among Seropositive African American MSM 50 Aged
Years and Older.
AB - Little is known about abuse experienced among African American men who have sex
with men (MSM) who are 50 years and older. A series of focus groups were
conducted to examine perspectives of seropositive African American MSM age 50
years and older who reported experiencing some form of psychological or physical
abuse. Thirty African American MSM were divided into four focus groups and four
themes emerged: "Fear Being Gay," "No One Else to Love Me," "Nowhere to Turn,"
and "Sexual Risk & Control." The data suggest there is a need to develop
culturally tailored interventions for this population.
PMID- 29333886
TI - Anaemia worsens early functional outcome after traumatic brain injury: a
preliminary study.
AB - OBJECTIVE: To determine early effects on outcome from traumatic brain injury
(TBI) induced by controlled cortical impact (CCI) associated with anaemia in
mice. HYPOTHESIS: Outcome from TBI with concomitant anaemia would be worse than
TBI without anaemia. METHODS: CCI was induced with electromagnetic impaction in
four groups of C57BL/6J mice: sham, sham+anaemia; TBI; and TBI+anaemia. Anaemia
was created by withdrawal of 30% of calculated intravascular blood volume and
saline replacement of equal volume. Functional outcome was assessed by beam
walking test and open field test (after pre-injury training) on post-injury days
3 and 7. After functional assessment, brains removed from sacrificed animals were
pathological reviewed with haematoxylin and eosin, cresyl violet, Luxol Fast
Blue, and IBA-1 immunostains. RESULTS: Beam-walking was similar between animals
with TBI and TBI+anaemia (p = 0.9). In open field test, animals with TBI+anaemia
walked less distance than TBI alone or sham animals on days 3 (p < 0.001) and 7
(p < 0.05), indicating less exploratory and locomotion behaviours. No specific
pathologic differences could be identified. CONCLUSIONS: Anaemia associated with
TBI from CCI is associated with worse outcome as measured by less distance
travelled in the open field test at three days than if anaemia is not present.
PMID- 29333888
TI - Primary Diffuse Large B-Cell Lymphoma of the Ciliary Body.
AB - PURPOSE: To report an unusual case of an eye with primary ciliary body lymphoma
which came to enucleation allowing detailed histopathological examination.
METHODS: A 50-year-old man presented with a painful loss of vision in the left
eye. The clinical, imaging, and immunohistopathological features of this case
were reviewed. RESULTS: The vision in the left eye was light perception. There
were keratic precipitates, an irregular and thickened iris with
neovascularization. Imaging studies disclosed a ciliary body mass extending into
the anterior chamber. The eye was enucleated and immunohistopathological
examination showed positive staining with CD20, BCL-2, MUM1, and CD10. Staining
with BCL-6 was weak and S100 and HMB45 expressions were negative. Occasional CD3+
reactive T cells were present. The Ki-67 index was 80-90%. All these results
suggested diffuse large B-cell lymphoma. CONCLUSIONS: Diffuse large B-cell
lymphoma may primarily arise from the ciliary body and can develop without
systemic or central nervous system disease.
PMID- 29333889
TI - Risking It Anyway: An Adolescent Case Study of Trauma, Sexual and Gender
Identities, and Relationality.
AB - This article presents the case of a Chinese-American adolescent with a
significant trauma history who was questioning her sexual and gender identities.
The implications of the client's intersecting identities for case
conceptualization and treatment are considered within the framework of
affirmative practices for sexual and gender minority (SGM) clients. The impacts
of stress and trauma on this client's experiences-and SGM clients more broadly
are also considered, particularly with respect to how this client understood and
negotiated her experiences of relational trauma. This case is intended to
illustrate some best practices with SGM clients within an intersectional
framework which underscores the importance of multiple salient cultural
identities.
PMID- 29333891
TI - Therapeutic Potential of Zataria multiflora Boiss in Treatment of Irritable Bowel
Syndrome (IBS).
AB - Irritable Bowel syndrome (IBS), the most common chronic functional
gastrointestinal disorder, is categorized as IBS-C and IBS-D, which are
equivalent to Ghoolenj Rihi and Maghs Rihi in Iranian traditional medicine. One
of the main applications of Zataria multiflora Boiss in traditional medicine is
its efficacy in the gastrointestinal tract with symptoms such as IBS. The aim of
this study was to evaluate the efficacy of Zataria multiflora essential oil in
management of IBS. We used all the accessible references (electronic and
published books, theses, and reports) to write this article. The results of our
investigation show that the majority of gas chromatography-mass spectrometry (GC
MS) analyses exhibited carvacrol and thymol as the main components of Zataria
multiflora essential oil, and 60 drops oral daily dose of Z. multiflora essential
oil (2%) can relieve the symptoms of IBS without any adverse effects. The
pharmacological studies confirmed the analgesic, anti-inflammatory, antispasm and
antiulcer effects of Z. multiflora essential oils and main components. According
to the results of studies, oral Z. multiflora essential oil (2%) is a good
candidate for management of IBS, but more studies are required to better
understand its efficacies.
PMID- 29333890
TI - Cigarette smoking and quit attempts among Latinos in substance use disorder
treatment.
AB - BACKGROUND: Differences in tobacco use behaviors have been identified between
Latinos and non-Latino whites in the general US population. Little is known about
cigarette smoking and quitting behaviors of Latinos in treatment for substance
use disorders (SUDs), who represent two major tobacco-vulnerable groups.
OBJECTIVES: To compare, in a national sample of persons enrolled in SUD
treatment, demographic, drug use, and smoking and quitting prevalence and
behaviors between Latinos and non-Latino whites. METHODS: We surveyed 777 SUD
treatment clients, sampled from 24 clinics selected at random from the National
Institute on Drug Abuse Clinical Trials Network (Latino client n = 141; 40%
female). We then conducted univariate and multivariate analyses to identify
correlates of smoking behaviors by Latino/non-Latino white ethnicity. RESULTS:
Latinos' smoking prevalence resembled that of non-Latino whites (78.7% vs.
77.4%). In regression analyses, Latino smokers (n = 111) tended to smoke fewer
cigarettes per day (CPD) than non-Latino white smokers (n = 492); were more often
nondaily smokers and menthol smokers; more often reported a smoking quit attempt
in the last year; and tended to report higher numbers of past-year quit attempts.
Among Latino smokers, those with less education and those reporting opioids as
their primary drug of use reported higher CPD. CONCLUSIONS: Latinos in SUD
treatment are at equally high risk of being current heavy smokers as compared to
non-Latino whites in SUD treatment. At the same time, Latinos in SUD treatment
exhibit ethnic-specific smoking and quitting behaviors that should be considered
when designing smoking interventions for this group.
PMID- 29333892
TI - Education Needs of Families of Transgender Young People: A Narrative Review of
International Literature.
AB - Education plays a crucial role in the lives of families of transgender young
people and mental healthcare practitioners are well-placed to support families in
this regard. This paper reports findings from a narrative review of 31 papers
that explored the education needs of families of transgender young people. The
emergent themes were synthesised to develop a five-stage model that depicts the
role of education in the lives of these families. Key themes included: (i)
learning that a family member is trans; (ii) family responses; (iii) accessing
education and information; (iv) impact on the individual; and (iv) moving beyond
the individual. The key implications for mental health practitioners, families,
and future research are discussed.
PMID- 29333893
TI - Syringe Administration of Epinephrine by Emergency Medical Technicians for
Anaphylaxis.
AB - OBJECTIVE: In recent years, the costs of epinephrine autoinjectors (EAIs) in the
United States have risen substantially. King County Emergency Medical Services
implemented the "Check and Inject" program to replace EAIs by teaching emergency
medical technicians (EMTs) to manually aspirate epinephrine from a single-use 1
mg/mL epinephrine vial using a needle and syringe followed by prehospital
intramuscular administration of the correct adult or pediatric dose of
epinephrine for anaphylaxis or serious allergic reaction. Treatment was guided by
an EMT protocol that required a trigger and symptoms. We sought to determine if
the "Check and Inject" program was safely implemented by EMTs treating presumed
prehospital anaphylaxis or serious allergic reaction. METHODS: We conducted a
prospective investigation of all cases treated as part of the "Check and Inject"
program from July 2014 through December 2016 in suburban King County, Washington,
and January 2016 through December 2016 within the city of Seattle. All cases were
prospectively collected using a custom quality improvement data form completed by
the first responding EMTs. Two physicians completed a structured review of each
EMS medical record to determine if the EMTs followed the Check and Inject
protocol and determine if epinephrine was clinically-indicated based on physician
review. RESULTS: Of the 411 cases eligible for analysis, EMTs followed the
protocol appropriately in 367 (89.3%) cases. In the remaining 44 (10.7%) cases,
the EMS incident report form failed to document either a clear inciting allergic
trigger or an appropriate symptom from the protocol list. Physician review
determined that epinephrine was clinically indicated in 36 of the 44 cases. Among
the remaining 8 cases (1.9%) that did not meet protocol criteria and were not
clinically-indicated based on physician review, none had a documented adverse
reaction to the epinephrine. CONCLUSION: We observed that EMTs successfully
implemented the manual "Check and Inject" program for severe allergic reactions
and anaphylaxis in a manner that typically agreed with physician review and
without any overt identified safety issues.
PMID- 29333895
TI - Childhood Adversity and Hazardous Drinking: The Mediating Role of Attachment
Insecurity.
AB - BACKGROUND: Harmful alcohol use is associated with disease and mortality.
Identifying new determinants of harmful drinking may aid the 16.3 million adults
who have alcohol use disorders. Childhood adversity is associated with alcohol
use, but is not amenable to change. Attachment insecurity (anxiety and avoidance)
may be associated with alcohol use and may be a target for modification or used
to personalize interventions. OBJECTIVES: This study aims to (a) identify the
association between attachment insecurity and harmful drinking, (b) determine if
attachment insecurity may mediate between childhood adversity and harmful
drinking, and (c) test sex as a moderator between attachment insecurity and
harmful drinking in the mediation relationship. METHODS: Adult primary care
patients (N = 348, 60% women) completed a cross-sectional survey study using
validated measures in 2012. Statistical analyses were performed using Hayes's
PROCESS macro in SPSS. RESULTS: Childhood adversity was reported by 61% of the
cohort and 18% endorsed harmful drinking. Attachment anxiety was associated with
harmful drinking (p >.001), but attachment avoidance was not (p =.11). Attachment
anxiety may mediate between childhood adversity and harmful drinking (95% CI:.03
.14). Sex did not moderate the relationships between attachment anxiety and
harmful drinking in the mediation relationship (women: 95% CI:.031-.179; men: 95%
CI:.003.-.182). Conclusions/Importance: Attachment anxiety may mediate between
childhood adversity and harmful drinking in both men and women. Attachment
anxiety may be a potential therapeutic target for people with a history of
childhood adversity.
PMID- 29333896
TI - Cataract Surgery in HIV Seropositive Patients: Long-Term Follow-Up.
AB - PURPOSE: To study epidemiology and clinical findings of cataract in HIV+
patients. METHODS: A total of 32 HIV+ patients, 11 with uveitis/retinitis before
surgery and 21 without, mean follow-up 44.9 +/- 36.6 months, and 114 HIV-
patients, 57 with uveitis/retinitis before surgery and 57 without, were
retrospectively compared. RESULTS: Visual acuity improved in all HIV+ patients (p
< 0.001), who were younger (p = 0.01) and more frequently males (p = 0.027). HIV+
patients with uveitis prior surgery improved less (p = 0.046) than HIV- (p <
0.001); their anterior chamber inflammation was similar to baseline. Male sex (p
= 0.005), younger age (p < 0.001), dyslipidaemia (p = 0.058), HBV+ (p = 0.037),
and unilateral cataract (p = 0.001) were more frequent in HIV+ patients with
senile cataract, but they showed the same postoperative course as HIV- patients.
CONCLUSION: Cataract surgery in HIV+ patients is safe and effective. Uveitis
prior to surgery did not significantly affect the postoperative course. Systemic
comorbidities are more frequent in HIV+ patients with senile cataract than in HIV
subjects.
PMID- 29333897
TI - Adherence to the American Diabetes Association retinal screening guidelines for
population with diabetes in the United States.
AB - PURPOSE: (1) To assess long-term adherence to American Diabetes Association
guideline-recommended retinal screening among population with diabetes in the
United States. (2) To determine factors associated with long-term adherence to
routine eye screening exams. METHODS: A retrospective cohort study was conducted
in adult patients with diabetes identified from January 2009 to December 2010.
Patients were followed until disenrollment, death, or study end date (December
2013). A patient was defined as adherent when having at least one exam in each 12
month period if there was evidence of retinopathy, or at least one exam in each
24-month period if there was no evidence of retinopathy. Multivariate logistic
regressions were used to investigate patient demographics and other baseline
characteristics associated with adherence to guidelines. RESULTS: A total of
204,073 patients were identified; the mean age (SD) was 61 (13) years and 48%
were female. Overall, 71.1% were adherent to the retinal screening guidelines
during a median of 4.8 years of follow-up including 27.7% who received an eye
exam every year. Patient socioeconomic status (younger age, black race, lower
income/education), less comorbidity, insulin use, higher specialist copayment
plans, and proxies for poor patient behavior (lower adherence to the oral
hypoglycemic agents, less diabetes education, hemoglobin A1C >9%) were associated
with nonadherence to routine eye screening exams. CONCLUSION: During nearly 5
years of follow-up, 28.9% of patients with diabetes were nonadherent to the
retinal screening guidelines. Future research should focus on the development of
interventions to address modifiable factors associated with nonadherence.
PMID- 29333898
TI - The Physical Health of Individuals Receiving Antipsychotic Medication: A
Qualitative Inquiry on Experiences and Needs.
AB - Individuals with a mental illness are reported to have a reduced life expectancy
and a greater risk of being affected by preventable physical illnesses such as
cardiovascular disease and Type 2 diabetes. This inquiry sought to identify the
physical health beliefs, experiences and needs of individuals with mental health
problems in receipt of antipsychotic medication who live in the community. A
qualitative inquiry was undertaken using three focus groups in a community mental
health service in Ireland with 21 participants with mental health problems who
were treated with antipsychotic medication. The participants were clear about the
importance of good physical health as well as good mental health. They disliked
the adverse effects of antipsychotic medication and experienced many barriers in
accessing general practitioners/primary care services. They also preferred to
receive health advice and self-management advice from the mental health services.
The participants in this study were aware of the need to engage in health
protective behaviours but were often overwhelmed by their comorbid health issues
and the organizational and communication barriers in accessing their general
practitioners.
PMID- 29333899
TI - Social Support and Mental Health in LGBTQ Adolescents: A review of the
literature.
AB - LGBTQ adolescents experience higher rates of mental health disorders than their
heterosexual peers. The purpose of this systematic review of the literature was
to examine studies evaluating social support and its effects on mental health in
the LGBTQ adolescent population. Higher levels of social support were associated
with positive self-esteem. Lack of social support (or low social support) was
associated with higher levels of depression, anxiety, alcohol or drug misuse,
risky sexual behaviors, shame, and low self-esteem. Interdisciplinary research
teams from multiple and diverse professions could provide valuable insight
supporting the development of inclusive and comprehensive interventions programs
for this population.
PMID- 29333900
TI - Stability of two anterior fixations for three-column injury in the lower cervical
spine: biomechanical evaluation of anterior pedicle screw-plate fixation.
AB - Objectives This study aimed to evaluate the stability of anterior pedicle screw
plate (APSP) fixation and anterior vertebral body screw-plate (AVBSP) fixation
for three-column injury in the lower cervical spine. Methods Six fresh-frozen
human cadaveric specimens of the lower cervical spine were prepared. After
measurement of the range of motion (ROM) in the intact state, the specimens were
prepared as three-column injury models. The models were stabilized by AVBSP or
APSP fixation. The ROM of the models in the two states was measured. The ROM in
the two states was compared. Results The ROM of the intact state in all
directions was significantly smaller than that of the AVBSP state and
significantly larger than that of the APSP state. The ROM of the AVBSP state in
all directions was significantly larger than that of the APSP state. Conclusions
This study shows that APSP fixation can provide sufficient stability for three
column injury in the lower cervical spine. The primary stability of our models
using APSP fixation is superior to that of AVBSP fixation. These results suggest
that APSP can be used for three-column injury in the lower cervical spine.
PMID- 29333901
TI - HER2 positive bilateral metachronous primary breast carcinoma: A case report.
AB - Human epidermal growth factor receptor 2 (HER2) positive is a unique molecular
subtype of breast cancer (BC) characterized by high malignancy and poor
prognosis. Bilateral primary breast cancer (BPBC) harboring HER2 gene
amplification is available to be detected among the BC survivors due to the
increasing use of anti-HER2 adjuvant therapy. However, owing to the paucity of
cases reported, knowledge of treating HER2-positive BPBC patients including the
clinical behavior, histopathologic characteristics, anti-HER2 therapeutic
response and disease outcome are not fully understood. Here we report a case of
its kind receiving nonstandardized treatment during adjuvant stage. Upon tumor
recurrence with liver metastasis, she received trastuzumab combined with
chemotherapy and reached a PFS of 14.5 months in first-line treatment. While
maintained trastuzumab plus carboplatin as second-line treatment progressed
promptly, re-treatment of trastuzumab after lapatinib administration in third
line can still benefit the patient. The present case report delineates an anti
HER2 path for a particular characterized patient, and also provides new evidence
of trastuzumab re-usage after disease progression of prior anti-HER2 therapy.
PMID- 29333902
TI - Patterns of NPS Use and Risk Reduction in Slovenia.
AB - BACKGROUND: The following study presents factors influencing the decision to
use/not to use new psychoactive substances (NPS), various patterns of NPS use,
the problems experienced by users, and the methods for reducing the risks
associated with NPS use. OBJECTIVES: The study seeks to provide an in-depth look
into the characteristics of NPS use and support the planning of targeted
interventions in the field of NPS. METHODS: The study involved 19 in-depth
interviews carried out with 25 individuals divided into three subsamples in order
to gain insight into the various experiences of NPS users. The interviews were
conducted in Slovenia between December 2013 and October 2014. The sample was
obtained by using the convenience sampling and snowball sampling methods.
RESULTS: The main pattern of NPS use determined by the study concerned synthetic
cathinones, specifically 3-MMC, with binge use spanning several days being a
prominent feature. The main risks involving NPS use were: mixing various drugs,
inappropriate dosing, lack of information prior to use, and the use of unknown
substances. Several users spoke about effective strategies for reducing risks,
such as obtaining information beforehand, using one's own implements and using
only small quantities of unknown substances. Conclusions/Importance: The study
revealed various factors based on which users decide to use NPS. Furthermore,
users reported a number of problems resulting from NPS use, while risk reduction
strategies are employed to a much lesser extent. Based on the results obtained,
specific intervention efforts concerning NPS use and targeting specific groups of
younger users were designed.
PMID- 29333903
TI - The First Report of Relative Incidence of Inherited White Matter Disorders in an
Asian Country Based on an Iranian Bioregistry System.
AB - Childhood leukodystrophies are a fast-growing field of pediatric neurology
practice. Epidemiologic studies on the incidence of these disorders in children
show different results. This is the first report of childhood leukodystrophies
incidence from Iran. The enrolled patients were recruited from the neurometabolic
bioregistry system that was organized in 2010 in the Children's Medical Center,
Tehran, Iran. Herein is reported the incidence rate of leukodystrophies in those
patients who were residents of 2 big popular provinces near Iran's capital city
Tehran, with an average child population of 2 988 800 children. Ninety cases of
leukodystrophies from Tehran and Alborz provinces who were registered between
2010 and 2016 in the bioregistry system were enrolled in this study. The annual
incidence of inherited white matter disorders was 3.01/100 000, the highest
number compared with those found in other studies using similar methods
throughout the world. One of the main cause of this higher incidence could be the
higher number of consanguineous marriages in Iran.
PMID- 29333904
TI - The biological treatment planning evolution of clinical fractionated radiotherapy
using high LET.
AB - Starting from the birth of high linear energy transfer (LET) radiotherapy in USA
in the mid-1970s, the field has continuously evolved and to date over 20,000
patients have been treated with 12C ions worldwide. The purpose of this
contribution is to review the advancements in clinical fractionated radiotherapy
using high LET radiation in the last decades, with special focus on biological
treatment planning. Along with technological developments for ion acceleration
and beam delivery, progress in radiation biology and computational modeling has
enabled a remarkable evolution in the planning capabilities of highly conformal,
biologically optimized treatment with high LET radiation. In particular, recent
efforts have provided the possibility of direct comparison between treatment
plans obtained at different facilities with different biological models for the
same ion species. This achievement represents an important step forward to gather
better understanding of the remaining uncertainties in biological modeling and
the impact of fractionation for optimal dose prescriptions, ultimately aiming to
promote clinical exploitation of the anticipated, yet not fully demonstrated
advantages of high LET-charged particles.
PMID- 29333905
TI - Linear nevus sebaceous syndrome presenting as circumscribed choroidal hemangioma.
AB - A 4-year-old female with a unilateral circumscribed choroidal hemangioma and
secondary total exudative retinal detachment. A nasal skin scar-like lesion
incised to confirm a histopathologic diagnosis of linear nevus sebaceous. Further
imaging disclosed asymmetry of the lateral ventricle frontal horns, suggestive of
the diagnosis of linear nevus sebaceous syndrome. The choroidal hemangioma was
treated with I-125 episcleral brachytherapy (apical dose of 45 Gy). At 6 months
post-radiation, the tumor showed regression with total resolution of exudative
retinal detachment.
PMID- 29333906
TI - TUBB1 variants and human platelet traits.
PMID- 29333907
TI - Quantitative methods in interprofessional education research: some critical
reflections and ideas to improving rigor.
PMID- 29333908
TI - False positive acetylcholine receptor antibodies in a case of unilateral chronic
progressive external ophthalmoplegia: case report and review of literature.
AB - METHODS: We present a rare case with atypical presenting features of unilateral
CPEO with a false positive Acetylcholine Receptor Antibody (AchRA) test resulting
in diagnostic delay. We illustrate the unilateral nature of this case and
demonstrate the caveats of performing myogenic ptosis correction in such
patients. We also discuss the differential diagnosis of false positive AchRA, a
test commonly performed in the investigation of ptosis. RESULTS: A 34-year old
female presented with a more than 3-year history of slowly-progressive,
unilateral, right-sided restriction in eye movements and ptosis. Clinical
examination showed EOM were grossly restricted in the right eye with a ptosis and
normal in the left eye. Serum AchRA was positive on serum enzyme-linked
immunosorbent assay (ELISA) however, following two months of oral pyridostigmine
therapy there were no signs of clinical improvement. The initial serum sample
sent was retested for AchRA by radio-immunoassay (RIA) which came back negative.
Subsequently a muscle biopsy was requested which showed the presence of ragged
red fibres. CONCLUSION: Unilateral ptosis and ophthalmoplegia is an unusual
presentation for CPEO which characteristically produces bilateral symmetrical
motility defects. In addition to Myasthenia Gravis elevated AchRA levels have
been reported in other autoimmune conditions such as Primary biliary cirrhosis,
Eaton Lambert syndrome and Graves's ophthalmopathy. We also highlight the
superiority of RIA versus ELISA in the detection of AchRA and illustrate the
diagnostic challenge of investigating and managing myogenic ptosis in this
complex cohort of patients.
PMID- 29333909
TI - Subclinical Inflammatory Response: Accelerated versus Standard Corneal Cross
Linking.
AB - PURPOSE: To compare the subclinical inflammatory response (as measured by
anterior chamber flare) induced after standard (3 mW/cm2, 30 min) and accelerated
(18 mW/cm2, 5 min) corneal cross-linking (CXL). METHODS: In this comparative, non
randomized study, patients with progressive keratoconus who underwent standard or
accelerated CXL were studied. Laser flare photometery (FM-600; Kowa, Tokyo,
Japan) was used to measure anterior chamber flare preoperatively and at 1 week, 1
month, 3 months, and 6 months after the procedure. RESULTS: Sixty eyes of 60
patients were studied; 30 eyes in each group. Mean baseline flare values were
4.15 +/- 1.19 and 4.57 +/- 2.17 ph/ms in standard and accelerated groups,
respectively (p = 0.228).and after surgery increased in all follow-up
measurements in the both groups similarly (P > 0.05). CONCLUSION: Both standard
and accelerated CXL results in induction of a subclinical inflammatory response
that persists up to 6 month. The response was similar between the two groups.
PMID- 29333910
TI - Soft Contact Lenses to Optimize Vision in Adults with Idiopathic Infantile
Nystagmus: A Pilot Parallel Randomized Controlled Trial.
AB - PURPOSE: The optimal management of infantile nystagmus syndrome (INS) is still
unclear. Contact lenses (CL) may be superior to glasses in improving visual
function in INS but it is not known whether their beneficial effects are due to
optical correction alone, or to an additional proprioceptive effect, and whether
soft CLs would be as effective as rigid CLs. There is little data on feasibility
and and the present study aimed to provide this information. METHODS: We
completed a pilot Randomized Control Trial (RCT) at a single tertiary referral
centre in London, UK. We enrolled 38 adults with idiopathic INS and randomised
them to either plano CL (with corrective spectacles if required) or to corrective
CL. CL wear was required for a minimum of 2 weeks. Primary outcome measures were
feasibility and safety of CL wear in INS; secondary outcome measures were visual
acuity and nystagmus waveform parameters. RESULTS: 27 completed the study
(27/38,71%). 4 partcipants withdrew due to difficulty with CL insertion/removal
and 7 were lost to follow up. CL tolerability was high (24/27,89%) - 2 found the
CLs irritant, and 1 had an exacerbation of allergic eye disease. At two weeks,
mean improvement in binocular visual acuity from baseline with plano CLs was 0.07
logMAR (95% confidence interval (CI: 0.03-0.11) and 0.06 logMAR with fully
corrective CLs (95% CI:0.02-0.1). Mean improvement in the eXpanded Nystagmus
Acuity Function (NAFX, a nystagmus acuity function based on eye movement
recording) with plano CLs was -0.04(95% CI: -0.08-0.005) and -0.05 with fully
corrective CLs(95% CI: -0.09-0.003). CONCLUSIONS: CLs are well tolerated, with a
low risk profile. Whilst our study was not powered to detect significant changes
in BCVA and waveform parameters between treatment arms, we observed a trend
towards an improvement in visual function at two weeks from baseline with CLs.
PMID- 29333911
TI - The Challenge of Pediatric Uveitis: Tertiary Referral Center Experience in the
United States.
AB - PURPOSE: To describe the distribution, clinical findings, visual outcomes,
treatment, and complications of children with uveitis at a tertiary referral
ophthalmic center. METHODS: Retrospective cohort study. We reviewed the medical
records of all patients <=16 years with uveitis referred to Massachusetts Eye
Research and Surgery Institution from March 2005 to July 2016. RESULTS: Of 286
included children, 62.24% were female. Mean age of onset was 8.4 years. The
uveitis was mainly anterior (61.9%), recurrent (68.53%), bilateral (81.82%), and
noninfectious (96.5%). Idiopathic cases accounted for 51.4%. The most frequent
systemic association was juvenile idiopathic arthritis (34.96%). The majority of
patients (78.32%) experienced complications. All patients, except one, needed
systemic therapy. CONCLUSION: Pediatric uveitis is challenging to diagnose and
manage, with frequent and potentially severe complications. Most cases were
bilateral, recurrent, and idiopathic. Prompt referral to uveitis-specialized
centers and an appropriate systemic therapy are mandatory for good visual
outcomes.
PMID- 29333912
TI - The resting-state fMRI arterial signal predicts differential blood transit time
through the brain.
AB - Previous studies have found that aperiodic, systemic low-frequency oscillations
(sLFOs) are present in blood-oxygen-level-dependent (BOLD) data. These signals
are in the same low frequency band as the "resting state" signal; however, they
are distinct signals which represent non-neuronal, physiological oscillations.
The same sLFOs are found in the periphery (i.e. finger tips) as changes in
oxy/deoxy-hemoglobin concentration using concurrent near-infrared spectroscopy.
Together, this evidence points toward an extra-cerebral origin of these sLFOs. If
this is the case, it is expected that these sLFO signals would be found in the
carotid arteries with time delays that precede the signals found in the brain. To
test this hypothesis, we employed the publicly available MyConnectome dataset (a
two-year longitudinal study of a single subject) to extract the sLFOs in the
internal carotid arteries (ICAs) with the help of the T1/T2-weighted images.
Significant, but negative, correlations were found between the LFO BOLD signals
from the ICAs and (1) the global signal (GS), (2) the superior sagittal sinus,
and (3) the jugulars. We found the consistent time delays between the sLFO
signals from ICAs, GS and veins which coincide with the blood transit time
through the cerebral vascular tree.
PMID- 29333913
TI - Boxing fatalities in relation to rule changes in Japan: secondary data analysis.
AB - OBJECTIVES: To examine whether changing weigh-in from the same day of the match
to the day before the match and prohibiting 6-oz gloves are associated with
fatalities in boxing matches sanctioned by the Japan Boxing Commission (JBC).
METHODS: We analyzed the rates of boxing fatalities before and after the two rule
changes above via secondary analysis of data. Demographics and boxing records of
deceased boxers were examined using descriptive statistics, exact binomial test
the Mann-Whitney-Wilcoxon test and Fisher's exact tests. RESULTS: As of this
study, a total of 38 boxers (23.9 +/- 3.3 years of age) reportedly died due to
injuries sustained in JBC-sanctioned boxing matches since 1952. Changing weigh-in
to the day before the match or prohibiting 6-oz gloves was not significantly
associated with the rates of boxing fatalities 5 years and 10 years before and
after the rule changes (p > 0.05). Deceased boxers after these rule changes were
significantly older, completed significantly more rounds in the final match, and
were significantly less likely to lose the previous match (prior to the final
match) and to do so by knockouts (p < 0.05). CONCLUSION: Changing weigh-in to the
day before the match and prohibiting 6-oz gloves may not result in reducing
boxing fatalities.
PMID- 29333914
TI - Hybrid PET/MRI imaging in healthy unsedated newborn infants with quantitative
rCBF measurements using 15O-water PET.
AB - In this study, a new hybrid PET/MRI method for quantitative regional cerebral
blood flow (rCBF) measurements in healthy newborn infants was assessed and the
low values of rCBF in white matter previously obtained by arterial spin labeling
(ASL) were tested. Four healthy full-term newborn subjects were scanned in a
PET/MRI scanner during natural sleep after median intravenous injection of 14 MBq
15O-water. Regional CBF was quantified using a one-tissue-compartment model
employing an image-derived input function (IDIF) from the left ventricle. PET
rCBF showed the highest values in the thalami, mesencephalon and brain stem and
the lowest in cortex and unmyelinated white matter. The average global CBF was
17.8 ml/100 g/min. The average frontal and occipital unmyelinated white matter
CBF was 10.3 ml/100 g/min and average thalamic CBF 31.3 ml/100 g/min. The average
white matter/thalamic ratio CBF was 0.36, significantly higher than previous ASL
data. The rCBF ASL measurements were all unsuccessful primarily owing to subject
movement. In this study, we demonstrated for the first time, a minimally invasive
PET/MRI method using low activity 15O-water PET for quantitative rCBF assessment
in unsedated healthy newborn infants and found a white/grey matter CBF ratio
similar to that of the adult human brain.
PMID- 29333915
TI - Gaze avoidance and perseverative language in fragile X syndrome and autism
spectrum disorder: brief report.
AB - Gaze avoidance and perseverative language impact pragmatics in autism spectrum
disorder (ASD) and fragile X syndrome (FXS). We examined these features during
conversation samples in boys with ASD (n = 10) and boys with FXS and ASD
(FXS+ASD; n = 10). Both groups had similar high rates of gaze avoidance and topic
and conversation device perseverations, yet these features were not correlated
with one another. Boys with FXS+ASD produced a higher proportion of single
utterance perseverations. Results from this study highlight the need for future
research to identify potential mechanisms influencing the presence of language
perseverations and gaze avoidance.
PMID- 29333917
TI - Role of cortical microbleeds in cognitive impairment: In vivo behavioral and
imaging characterization of a novel murine model.
AB - Cerebral microbleeds (CMBs) could contribute to cognitive impairment in the
general population and in patients with dementia. We designed a study to (i)
develop a murine model of CMBs, (ii) assess whether CMBs affect cognition in this
model and (iii) assess whether this model is sensitive to pharmacological
modulation. Male C57Bl6/J mice were stereotactically administered collagenase to
induce cortical lesion analysed by MRI at 24 h. CMB-mice were assessed at six
weeks post-lesion for cognitive performances (Barnes maze and Touchscreen
automated paired-associated learning (PAL) task) and for cerebral metabolism (in
vivo PET/CT with fluorodeoxyglucose (FDG)). CMB-model sensitivity to
pharmacological modulation was assessed by administering atorvastatin (5
mg/kg/day) over the follow-up period. CMB mice were compared to naive
littermates. Collagenase at 0.8 uU/ul appeared suitable to induce reproducible
and reliable CMBs. At six weeks, a decline in learning, spatial and visuospatial
memory was significantly observed in CMB-mice. Brain metabolism was impaired in
all cortex, striatum and the ipsilateral dentate gyrus. A significant improvement
in cognition performances was depicted under atorvastatin. In this novel murine
model of CMBs, we validated that CMBs lowered cognitive performances and affected
regional metabolism. We also proved that this CMB-model is sensitive to
pharmacological modulation.
PMID- 29333918
TI - Modified second stage Hughes tarsoconjunctival reconstruction for lower eyelid
defects.
AB - To describe a novel technique utilizing an amniotic membrane graft (AMT) to
create the mucocutaneous portion of the lower eyelid margin in a modified Hughes
eyelid reconstruction for secondary revision or prevention of a hyperemic,
hypertrophic conjunctival margin with excessive discharge. This was a
retrospective, non-comparative interventional study. Thirty consecutive patients
who underwent a modified Hughes reconstruction were included. The first step of
the reconstruction was performed in a standard fashion using a tarsoconjunctival
flap from the ipsilateral upper eyelid. The second stage was accomplished by the
division of the tarsoconjunctival flap. The modification of the procedure
included the addition of AMT (Ambio 5(r), IOP Ophthalmics, CA) to the new
mucocutaneous junction. Main outcome measures included the post Mohs surgery
defect size, post-reconstruction complications. One patient received AMT for a
revision of a hyperemic lid margin following reconstruction, while 29 subsequent
patients received AMT as a primary procedure. The mean size of the post-Mohs
defect was 23.75 +/- 6.6 mm2 horizontally and 9.1 +/- 5.4 mm2 vertically,
involving 79.53 +/- 16.8% of the lower eyelid. There was no evidence of hyperemic
or hypertrophic margin at a mean follow-up of 4.41 +/- 2.91 months. The addition
of an AMT for the revision, or as a primary procedure for prevention of a
hyperemic, hypertrophic eyelid margin with excess mucus production in the post
Hughes lower eyelid reconstruction has favorable outcomes in this preliminary
study, however warrants further investigation with larger number of patients and
longer follow-up.
PMID- 29333916
TI - Cytoplasmic collagen XIalphaI as a prognostic biomarker in esophageal squamous
cell carcinoma.
AB - Stromal/cytoplasmic collagen XIalphaI (COL11A1) has been highlighted in the
process of neoplastic transformation, including epithelial mesenchymal transition
(EMT), metastasis and invasiveness. In this study, we aim to illuminate the
clinical significance and biological role of COL11A1 in esophageal squamous cell
carcinoma (ESCC). Herein, we investigated COL11A1 expression in 16 pairs of ESCC
and adjacent normal tissues by RT-PCR and western blotting analysis. Correlations
of COL11A1 expression with clinicopathologic parameters and survival status were
then determined by immunohistochemistry in 116 ESCC and 50 normal specimens.
Furthermore, bioinformatics was used for mechanisms exploration. And in vitro
knockdown experiments were also performed. We found that COL11A1 expression was
significantly higher in ESCC than in paired normal tissues at both mRNA and
protein level. Immunohistochemistry showed that COL11A1 was predominantly
localized to the cytoplasm rather than tumor stroma, patients with high COL11A1
expression had a poorer overall survival (OS) rate than those with low COL11A1
expression. Besides, increased COL11A1 expression was dramatically correlated
with advanced clinical stage, invasion depth and lymph node metastases and served
as an independent prognostic marker for ESCC. Likewise, COL11A1 dependent
nomogram predicted a more precise survival outcome than traditional staging
system. Moreover, COL11A1 silencing resulted in impaired cell proliferation and
EMT, and subdued EMT inhibited cells aggressiveness. These biological processes
(BPs) might be modulated by COL11A1 via the intracellular AKT/ERK/c-Myc cascades.
PMID- 29333919
TI - Reconstruction of extensive medial canthal defects using a single V-Y, island
pedicle flap.
AB - The medial canthus represents one of the most challenging regions of the face to
reconstruct due to the anatomical structures present, the concavity of the area,
and the differences in skin texture. We present a case series of 11 patients
whose defects were reconstructed with a single V-Y island pedicle flap running
along the nasofacial sulcus. Our single-stage flap which modified and simplified
a previously described technique achieves similar cosmetic and postoperative
outcomes along with a high level of patient satisfaction in an area which can be
reconstructed in a variety of ways, often with suboptimal results.
PMID- 29333920
TI - Towards a psychology of sexual health.
PMID- 29333921
TI - Targeting BRD4 proteins suppresses the growth of NSCLC through downregulation of
eIF4E expression.
AB - Lung cancer is the leading cause of cancer-related death worldwide. Bromodomain
and extraterminal domain (BET) proteins act as epigenome readers for gene
transcriptional regulation. Among BET family members, BRD4 was well studied, but
for its mechanism in non-small cell lung carcinoma has not been elucidated. eIF4E
regulates gene translation and has been proved to play an important role in the
progression of lung cancer. In this study, we first confirmed that BET inhibitors
JQ1 and I-BET151 suppressed the growth of NSCLCs, in parallel with downregulated
eIF4E expression. Then we found that knockdown of BRD4 expression using siRNAs
inhibited the growth of NSCLCs as well as decreased eIF4E protein levels.
Moreover, overexpression of eIF4E partially abrogated the growth inhibitory
effect of JQ1, while knockdown of eIF4E enhanced the inhibitory effect of JQ1.
Furthermore, JQ1 treatment or knockdown of BRD4 expression decreased eIF4E mRNA
levels and inhibited its promoter activity by luciferase reporter assay. JQ1
treatment significantly decreased the binding of eIF4E promoter with BRD4.
Finally, JQ1 inhibited the growth of H460 tumors in parallel with downregulated
eIF4E mRNA and protein levels in a xenograft mouse model. These findings suggest
that inhibition of BET by JQ1, I-BET151, or BRD4 silencing suppresses the growth
of non-small cell lung carcinoma through decreasing eIF4E transcription and
subsequent mRNA and protein expression. Considering that BET regulates gene
transcription epigenetically, our findings not only reveal a new mechanism of BET
regulated eIF4E in lung cancer, but also indicate a novel strategy by co
targeting eIF4E for enhancing BET-targeted cancer therapy.
PMID- 29333923
TI - Perception and Practice of HIV/AIDS Counseling and Testing Among Secondary School
Adolescents in Ogun Waterside Local Government Area, Ogun State, Southwest
Nigeria.
AB - A large proportion of Nigerian adolescents are sexually active and the country
has one of the highest HIV prevalence among youths globally. This study was done
to assess the perception and practice of HIV/AIDS counseling and testing (HCT)
among secondary school adolescents in a rural community in Southwest Nigeria. A
cross-sectional descriptive study was carried out using multistage sampling
method. The results showed that despite high level of HCT awareness, majority of
the adolescents (62.9%) had negative attitude toward it. The practice of HCT was
poor among majority of the respondents as less than 15% of the adolescents had
ever done HCT. This study recommends that adolescents should be better informed
on the locations of the health centers within the community and services rendered
by them. Peer education on HCT should also be intensified in schools to promote
positive healthy sexual lifestyles among adolescents.
PMID- 29333922
TI - Effect of resveratrol treatment on graft revascularization after islet
transplantation in streptozotocin-induced diabetic mice.
AB - We evaluated the effect of resveratrol (RSV) on graft survival after islet
transplantation (ITx) in diabetic mice. Isolated islets from Balb/c mice (200
IEQ) were transplanted under the kidney capsule of diabetic Balb/c mice. Vehicle
or RSV (200 mg/kg/day, orally) was given for 14 days after ITx. Two more control
groups [STZ-treated (No-ITx-Control) and STZ+RSV-treated (No-ITx-RSV) mice
without ITx] were added. Glucose tolerance tests (GTT) was performed at 14 days
after ITx. In vitro, isolated islets pretreated with vehicle or RSV (1 MUM) were
incubated in a hypoxic chamber (O2 1%, 1hr). Some of the ITx was performed in
mouse insulin 1 gene promoter-green fluorescent protein (MIP-GFP) transgenic mice
and analyzed using an in vivo imaging system. After 14 days of ITx, 2-hr glucose
levels on GTT in the RSV-treated group were significantly lower than those of
other control groups. But the glucose status was not improved in No-ITx mice with
RSV. At day 3, the percentage of Ki-67/insulin co-stained cells in islet graft
was significantly increased in the RSV-ITx group. Immunostaining with anti
insulin and anti-BS-1 antibodies revealed significantly higher insulin-stained
area and vascular density in RSV-treated islet grafts. The mean vessel volume per
islet graft measured by in vivo imaging was significantly higher in the RSV
treated group at day 3. In isolated islets cultured in hypoxic conditions, the
cell death rate and oxidative stress were significantly attenuated with RSV
pretreatment. Hypoxic treatment for isolated islets decreased the expression of
SIRT-1 mRNA, and this attenuation was recovered by RSV pretreatment. Our data
suggest that RSV treatment improved glycemic control, beta-cell proliferation,
reduced oxidative stress, and enhanced islet revascularization and the outcome of
ITx in diabetic mice.
PMID- 29333924
TI - Dynamic MR imaging for functional vascularization depends on tissue factor
signaling in glioblastoma.
AB - Glomeruloid vascular proliferation (GVP) is a diagnostic hallmark and links to
aggressive behavior, therapy resistance and poor prognosis in glioblastoma (GBM).
It lacks clinical approaches to predict and monitor its formation and dynamic
change. Yet the mechanism of GVPs also remains largely unknown. Using an in situ
GBM xenograft mouse model, combined clinical MRI images of pre-surgery tumor and
pathological investigation, we demonstrated that the inhibition of tissue factor
(TF) decreased GVPs in Mouse GBM xenograft model. TF shRNA reduced microvascular
area and diameter, other than bevacizumab. TF dominantly functions via PAR2/HB
EGF-dependent activation under hypoxia in endothelial cells (ECs), resulting in a
reduction of GVPs and cancer cells invasion. TF expression strongly correlated to
GVPs and microvascular area (MVA) in GBM specimens from 56 patients, which could
be quantitatively evaluated in an advanced MRI images system in 33 GBM patients.
This study presented an approach to assess GVPs that could be served as a MRI
imaging biomarker in GBM and uncovered a molecular mechanism of GVPs.
PMID- 29333925
TI - Androgen receptor-independent prostate cancer: an emerging clinical entity.
AB - Androgen deprivation therapy remains the backbone of prostate cancer treatment
given its pivotal role in the pathogenesis of prostate cancer. The growing
knowledge of androgen receptor-independent (i.e. AR-null) prostate cancer cells,
however, might advance the treatment paradigm of prostate cancer. Here, we
examined the results of two recent studies, published in Cancer Cell by Bluemn
and Shukla et al., and their impact in the future management of castration
resistant prostate cancer.
PMID- 29333926
TI - Engrailed 1 overexpression as a potential prognostic marker in quintuple-negative
breast cancer.
AB - Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype
characterized by poor patient prognosis and for which no targeted therapies are
currently available. TNBC can be further categorized as either basal-like (BLBC)
or quintuple-negative breast cancer (QNBC). In the present study, we aimed to
identify novel molecular therapeutic targets for TNBC by analyzing the mRNA
expression of TNBC-related genes in publicly available microarray data sets. We
found that Engrailed 1 (EN1) was significantly overexpressed in TNBC. Using
breast cancer cell lines, we found that EN1 was more highly expressed in TNBC
than in other breast cancer subtypes. EN1 expression was analyzed in 199 TNBC
paraffin-embedded tissue samples by immunohistochemistry. EN1 protein expression
was positively associated with reduced overall survival (OS) rate in patients
with QNBC, but not those with BLBC. The importance of EN1 expression in QNBC cell
viability and tumorigenicity was evaluated using the QNBC cell lines, HCC38 and
HCC1395. Based on our data, EN1 may promote the proliferation, migration, and
multinucleation of QNBC cells, likely via the transcriptional activation of
HDAC8, UTP11L, and ZIC3. We also demonstrated that actinomycin D effectively
inhibits EN1 activity in QNBC cells. The results of the present study suggest
that EN1 activity is highly clinically relevant to the survival prognosis of
patients with QNBC and EN1 is a promising potential therapeutic target for future
QNBC treatment.
PMID- 29333927
TI - Comprehensive characterization of hydrothermal liquefaction products obtained
from woody biomass under various alkali catalyst concentrations.
AB - Hydrothermal liquefaction (HTL) of lignocellulosic biomass has been widely
investigated for the production of renewable and alternative bio-crude oil. In
this study, catalytic hydrothermal processing of two biomasses (larch and
Mongolian oak) was performed using different K2CO3 concentrations (0, 0.1, 0.5,
1.0 wt% of solvent) to improve fuel yield and properties. HTL oil, hydrochar,
water-soluble fraction (WSF) and gas were characterized, and carbon balance was
investigated. As a result, the maximum yield of HTL oil, 27.7 wt% (Mongolian oak)
and 25.7 wt% (larch), and the highest carbon conversion ratio was obtained with
0.5 wt% of catalyst. The high catalyst concentration also resulted in an increase
in higher heating values up to 31.9 MJ/kg. In addition, the amount of organic
compounds in HTL oil also increased, specifically for lignin-derived compounds
including catechol and hydroquinone which can be derived from secondary
hydrolysis of lignin. On the other hand, formation of hydrochar was suppressed
with the addition of alkali catalyst and the yield dramatically decreased from
30.7-40.8 wt.% to 20.0-21.8 wt.%. Furthermore, it was revealed that WSF had low
organic carbon content less than 3.4% and high potassium content mostly derived
from alkali catalyst, indicating that it may be reusable with simple
purification. This work suggests that the addition of the proper amount of alkali
catalyst can improve the production efficiency and quality of bio-crude oil, and
another potential of WSF to be recyclable in further work.
PMID- 29333929
TI - Efficacy of an imaging device at identifying the presence of bacteria in wounds
at a plastic surgery outpatients clinic.
AB - OBJECTIVE: Current standard diagnostic practice of bacterial infections by visual
inspection under white light is subjective, and microbiological sampling is
suboptimal due to high false negative rates and the lengthy time needed for
culture results to arrive. The MolecuLight i:X Imaging Device attempts to combat
the issues faced in standard practice by providing a non-contact, real-time
method of visualising bacteria within wounds. Our aim was to test this imaging
device in a series of patients. METHOD: A single-centre prospective observational
study was conducted in the Queen Elizabeth Hospital, Birmingham. During Plastic
Surgery Outpatient dressings clinics, patients had their wounds photographed with
the imaging device under white light and violet light illumination.
Microbiological swabs were obtained of all the wounds. Any clinical signs and
symptoms of infection were noted. White light and violet light photographs were
compared with correlate visible clinical signs and symptoms with auto
fluorescence images. Auto-fluorescence images were then compared with the
microbiological swab results to discern any differences. RESULTS: There were 14
patients with seventeen separate wounds imaged. Of the 17, eight wounds were
positive for bacterial growth on microbiological culture. All eight of these were
detected positive for bacteria according to auto-fluorescence imaging. There was
one wound was detected positive for bacteria by auto-fluorescence imaging with
negative microbiological results. CONCLUSION: This study demonstrated the
potential benefit of the imaging device due to the correlation between
microbiological test results and auto-fluorescence imaging. The device greatly
reduces the time taken waiting for results and it is simple, quick to use and non
contact. There is potential for the imaging device to guide swab sampling and aid
health professionals in the diagnosis and management of wound infections.
PMID- 29333930
TI - A histological analysis of artificial skin in an extensively burned child, 14
years after application: a case report.
AB - INTRODUCTION: Artificial skin has become the treatment of choice in extensive,
full-thickness thermal injuries. The longest follow-up of the healing process in
burn sites covered with the Integra Bilayer Matrix Wound Dressing onto the wound
published to date was at around five years after application. In our case report,
we describe the clinical and histological analysis of an extensive, full
thickness thermal injury 14 years on from treatment with the bilayer matrix wound
dressing. CASE STUDY: A nine-year-old boy suffered a full-thickness skin loss
over 85% of his body surface area following a fire accident. The bilayer matrix
wound dressing was used on both legs and covered almost 30% of his body surface
area. Cosmetic and functional results were satisfactory. Histological analysis
performed nine years after the application of the bilayer matrix wound dressing
onto the wound showed a double-layered skin composition with changes in the
fibrous component of the dermis. CONCLUSION: Despite satisfactory short- and long
term clinical results from applications of the bilayer matrix wound dressing, we
found important differences in microstructure when compared with the
physiological condition.
PMID- 29333928
TI - Phosphorylation of STAT3 Promotes Vasculogenic Mimicry by Inducing Epithelial-to
Mesenchymal Transition in Colorectal Cancer.
AB - Vasculogenic mimicry refers to the process by which highly invasive cancer cells
mimic endothelial cells by forming blood channels. Vasculogenic mimicry is
important for the invasion and metastasis of tumor cells in colorectal cancer.
STAT3 was initially identified as a mediator of the inflammation-associated acute
phase response. The phosphorylation of Signal Transducers and Activators of
Transcription 3 (p-STAT3) is closely related to tumor invasion and migration. We
analyzed the relationship between p-STAT3 and vasculogenic mimicry formation in
65 human colorectal cancer samples, and the results showed that the expression of
p-STAT3 is significantly correlated with vasculogenic mimicry, tumor metastasis,
Tumor, Lymph Node and Metastasis Stage (TNM Stage), and poor prognosis. It is
known that interleukin 6 can induce the phosphorylation of STAT3. We found that
using interleukin 6 to induce p-STAT3 activation in colorectal cancer cell lines
can result in vasculogenic mimicry and using AG490 to suppress p-STAT3 activation
restrained vasculogenic mimicry. Furthermore, the state of p-STAT3 activation can
affect epithelial-to-mesenchymal transition. By immunofluorescence double
staining, we discovered that p-STAT3 expression is more directly correlated with
the epithelial-to-mesenchymal transition marker vimentin than with the
vasculogenic mimicry-related protein VE-cadherin. These data show that activated
p-STAT3 upregulates epithelial-to-mesenchymal transition-related proteins and
promotes vasculogenic mimicry.
PMID- 29333931
TI - Hyperspectral imaging of tissue perfusion and oxygenation in wounds: assessing
the impact of a micro capillary dressing.
AB - OBJECTIVE: Experimental tests of non-invasive multi- or hyperspectral imaging
(HSI) systems reveal the high potential of support for medical diagnostic
purposes and scientific biomedical analysis. Until now the use of HSI
technologies for medical applications was limited by complex and overly
sophisticated systems. We present a new and compact HSI-camera that could be used
in normal clinical practice. METHOD: We assessed the use of the HSI system on the
hands of 10 healthy volunteers, looking at control parameters, and those
following venous occlusion, arterial occlusion and reperfusion, including tissue
oxygenation, tissue haemoglobin index, perfusion in 4-6mm depth=near infrared
spectroscopy (NIR), and tissue water index. Pseudo colours used ranged from 0%
(blue) to 100% (red). We also assessed differences in the wounds of three
patients. RESULTS: The results show good potential in all parameters in the
healthy volunteers, which had high conformity with validated reference oximetry
measurements. In three wounds, different levels of oxygenation were identified in
the wound area, although interpretation of these results is complex. In Cases 2
and 3, following the application of a micro capillary dressing, improvements were
seen in perfusion and reduction of the tissue water index (TWI). CONCLUSION: The
camera system proved to be quick, flexible and yielded data with high spatial and
spectral resolution. These data will be used to perform a power analysis for a
randomised controlled study.
PMID- 29333932
TI - A comparison between DACC with chlorhexidine acetate-soaked paraffin gauze and
foam dressing for skin graft donor sites.
AB - OBJECTIVE: Retrograde infections often occur with excessive or incomplete
drainage of exudate, or as a result of adherence of dressings to wounds.
Dialkylcarbamoyl chloride (DACC) irreversibly binds to bacterial surfaces and
physically removes bacteria when dressings are changed. Chlorhexidine acetate
soaked paraffin gauze provides a moist wound-healing environment. We hypothesise
that when DACC is combined with chlorhexidine acetate-soaked paraffin gauze,
wound healing times decrease. METHOD: From January 2013 to June 2015, medical
records were retrospectively evaluated in 60 patients who underwent split
thickness skin grafts (STSG). Patients were divided into two groups: a 'thick
skin group' and a 'thin skin group'. These two groups were further subdivided
into a control group, where conventional foam dressings were applied to wounds,
and an experimental group, where chlorhexidine acetate-soaked paraffin gauze with
DACC was applied (DACC group). We compared the wound healing time between these
subgroups. Differences in infected wound healing times were also compared. The
Mann-Whitney test was applied to compare wound healing times between groups.
RESULTS: Epithelialisation duration was significantly shorter in the DACC group.
The control group had longer wound healing times, regardless of wound size. In
the thick skin group, the median healing duration was 12 days in the control
subgroup, compared with 9.5 days in the DACC subgroup (p=0.049). In the thin skin
subgroup, the median healing duration in the control group was 18 days, compared
with 10 days in the DACC subgroup (p=0.013). CONCLUSION: Application of DACC and
chlorhexidine acetate-soaked paraffin gauze to skin graft donor sites can shorten
healing times and is effective in treating infected wounds.
PMID- 29333933
TI - Inspiration: the forgotten element in improving skin health and wound healing?
PMID- 29333934
TI - Split-thickness skin grafting: early outcomes of a clinical trial using different
graft thickness.
AB - OBJECTIVE: In clinical practice, split-thickness skin graft (STSG)
transplantation remains the gold standard for covering large skin defects.
Currently, there is no consensus on the optimal thickness of skin grafts. The
purpose of our study was to compare the early healing processes of recipient and
donor wounds after STSG transplantation using grafts of different thickness.
METHOD: This prospective, randomised clinical trial included 84 patients that
underwent STSG transplantation surgery for post-burn, post-traumatic or
postoperative skin defects. Patients were randomised to receive a skin graft of
either 0.2mm, 0.3mm or 0.4mm thickness. After skin transplantation, the wound
healing parameters of both the recipient and donor wounds were evaluated after
three days, one week, two weeks and one month. RESULTS: The greatest mean
epithelialisation scores and highest rate of complete wound epithelialisation
were identified in the recipient and donor wounds of the 0.2mm transplant group,
at all time points. When the recipient wound pain scores were evaluated, the
greatest visual analogue scale (VAS) values were found in the 0.2mm transplant
group. The opposite result was found for the donor wound, where the highest VAS
scores were identified in the 0.4mm transplant group. There were no significant
differences, at any follow-up period, when wound secretion, erythema, swelling,
localised warmth and fluctuation were compared. CONCLUSION: The early healing of
recipient wounds after STSG transplantation with grafts of various thickness
differed considerably, especially regarding wound epithelialisation and pain.
PMID- 29333936
TI - Disseminated histoplasmosis: a rare case presentation.
PMID- 29333935
TI - Association between Human Papilloma Virus (HPV) vaccination and risk of Multiple
Sclerosis: A systematic review.
AB - INTRODUCTION: The vaccination against Humanpapilloma Virus (HPV) is an effective
strategy to prevent high-risk HPV infection and subsequent cervical
carcinogenesis. Although the safety profile has been ascertained, the relation
with the development of central nervous system (CNS) autoimmune disorders (AD)
appears still controversial. Multiple Sclerosis (MS) is the most common cause of
chronic neurological impairment in young people, typically striking females. The
main purpose of this review was to assess the association between HPV vaccination
and MS. METHODS: The systematic review of the literature was carried out using 5
search engines: MEDLINE, SCOPUS, ISI WEB OF KNOWLEDGE, GOOGLE SCHOLAR and
ClinicalTrial.gov. The web search was updated on January 2017. PRISMA checklist
was adopted to address the content of the systematic review. The measures of
outcome were reported as relative risk (RR) in cohort studies and odds ratio (OR)
in case-control studies. RESULTS: The systematic review identified 5
observational studies, 9 reviews, and 1 randomized clinical trials (RCT) pooled
analysis. The RR of MS onset detected by cohort studies ranged from 1.54 (95%CI,
0.04-8.59) to 1.37 (95%CI, 0.74-3.20). Concerning case-control studies, the OR
spanned from 0.3, (95%CI 0.1-0.9) to 1.60 (95%CI = 0.79-3.25) for the group
exposed to HPV vaccination. No result was significant. CONCLUSION: This review
showed no significant association between HPV vaccination and MS. The low
statistical power of the studies agreed with the low incidence of MS disease
among general population. In order to overcome the shortcoming the research may
be extended to the entire pattern of CNS ADs.
PMID- 29333937
TI - The Prevalence of Sexual Revictimization: A Meta-Analytic Review.
AB - The literature consistently demonstrates evidence that child sexual abuse
survivors are at greater risk of victimization later in life than the general
population. This phenomenon is called sexual revictimization. Although this
finding is robust, there is a large amount of variability in the prevalence rates
of revictimization demonstrated in the literature. The purpose of the present
meta-analysis was to calculate an average prevalence rate of revictimization
across the literature and to examine moderators that may potentially account for
the observed variability. Based on a review of PsycINFO and PILOTS, 1,412
articles were identified and reviewed for inclusion. This process resulted in the
inclusion of 80 studies, which contained 12,252 survivors of child sexual abuse.
The mean prevalence of sexual revictimization across studies was 47.9% (95%
confidence intervals [43.6%, 52.3%]), suggesting that almost half of child sexual
abuse survivors are sexually victimized in the future. The present study failed
to find support for any of the examined moderators. Potential explanations of and
implications for the results are offered, including suggestions for therapists.
PMID- 29333938
TI - Structure-based engineering to restore high affinity binding of an isoform
selective anti-TGFbeta1 antibody.
AB - Metelimumab (CAT192) is a human IgG4 monoclonal antibody developed as a TGFbeta1
specific antagonist. It was tested in clinical trials for the treatment of
scleroderma but later terminated due to lack of efficacy. Subsequent
characterization of CAT192 indicated that its TGFbeta1 binding affinity was
reduced by ~50-fold upon conversion from the parental single-chain variable
fragment (scFv) to IgG4. We hypothesized this result was due to decreased
conformational flexibility of the IgG that could be altered via engineering.
Therefore, we designed insertion mutants in the elbow region and screened for
binding and potency. Our results indicated that increasing the elbow region
linker length in each chain successfully restored the isoform-specific and high
affinity binding of CAT192 to TGFbeta1. The crystal structure of the high binding
affinity mutant displays large conformational rearrangements of the variable
domains compared to the wild-type antigen-binding fragment (Fab) and the low
binding affinity mutants. Insertion of two glycines in both the heavy and light
chain elbow regions provided sufficient flexibility for the variable domains to
extend further apart than the wild-type Fab, and allow the CDR3s to make
additional interactions not seen in the wild-type Fab structure. These
interactions coupled with the dramatic conformational changes provide a possible
explanation of how the scFv and elbow-engineered Fabs bind TGFbeta1 with high
affinity. This study demonstrates the benefits of re-examining both structure and
function when converting scFv to IgG molecules, and highlights the potential of
structure-based engineering to produce fully functional antibodies.
PMID- 29333939
TI - Parents' attitude, awareness and behaviour towards influenza vaccination in
Pakistan.
AB - National immunization program of Pakistan does not include Influenza vaccines.
The low rate of immunization might be attributed to the poor knowledge of
influenza vaccination in Pakistan. Current study was aimed to assess the
knowledge and attitude of influenza vaccination among parents. A questionnaire
based cross sectional study was conducted among randomly selected parents with at
least one child aged >6 months. The responses were recorded against 27 items
questionnaire assessing knowledge, perception, attitude and behaviours of
parents. Data were analysed by using appropriate statistical methods. A total 532
responses were recorded with male gender preponderance (65%). Most of the parents
(61.1%) reported that their children had received or planned to receive all
recommended vaccines in Expanded Program on Immunization (EPI) of Pakistan. Only
one third of the parents (24.4%) were aware of the availability of influenza
vaccines in Pakistan, and very few (6.6%) reported vaccinating their child
against influenza. Exploring the parents' attitudes regarding children
vaccination, the top motivator was 'immunization is important to keep my children
healthy' (relative index = 0.93, p < 0.000). However, substantial number of
parents believed that influenza is not a serious disease (18.5%) and vaccines are
accompanied by several side effects (24.6%). A positive attitude was reflected
among parents who were aware of influenza vaccines in Pakistan. About 35%
participants believed that influenza vaccines are not required for healthy
children. Current study demonstrated very low vaccination rate against influenza.
Awareness and health literacy regarding influenza vaccine is poor among parents.
These findings necessitate the need to appropriately structured awareness
programs regarding influenza vaccination among parents.
PMID- 29333940
TI - Expression analysis of liver-specific circulating microRNAs in HCV-induced
hepatocellular Carcinoma in Egyptian patients.
AB - OBJECTIVES: Due to the absence of reliable and accurate biomarkers for the early
detection of liver malignancy, circulating microRNAs have recently emerged as
great candidates for prompt cancer identification. Therefore, the aim of this
study was to investigate the potential of liver-specific circulating microRNAs as
an accurate non-invasive diagnostic tool for early diagnosis of hepatitis C virus
(HCV)-induced hepatocellular carcinoma (HCC). METHODOLOGY: A total of 165
patients were enrolled in this study and categorized into four main groups: 42
chronic hepatitis C (CHC) without cirrhosis, 45 CHC with cirrhosis (LC), 38 HCC
with HCV patients, and 40 healthy controls. The expression profiles of seven
miRNAs (miR-16, miR-34a, miR-125a, miR-139, miR-145, miR-199a, and miR-221) were
analyzed using real-time PCR. RESULTS: Serum levels of miRNA-125a, miRNA-139,
miRNA-145, and miRNA199a were significantly lower (p < 0.01) in HCC than in both
CHC and LC groups. On the other hand, no significant difference was shown in the
expression of miR-16, miR-34a, and miR-221 between the CHC, LC, and HCC groups.
MiR-16, miR-34a, and miR-221 were significantly elevated in the HCC group
compared to the control group. MiR-34a showed the highest specificity and
sensitivity. CONCLUSIONS: The results indicated that the measurement of serum
levels of miR-125a, miR-139, miR-145, and miR-199a can help to differentiate HCC
from CHC and LC. Also, miR-16, miR-34a, and miR-221 serum levels would have a
prognostic value. MiR-34a had the highest specificity and sensitivity, indicating
that it might serve as a novel and potential non-invasive biomarker for HCV
induced HCC.
PMID- 29333941
TI - Intraoperative Complications and Mid-Term Follow-Up of Large-Diameter Head Metal
on-Metal Total Hip Arthroplasty and Hip Resurfacing Arthroplasty.
AB - BACKGROUND AND AIMS: Large-diameter head total hip arthroplasty and hip
resurfacing arthroplasty were popular in Finland from 2000 to 2012 for the
treatment of hip osteoarthritis. The aim of this retrospective study was to
investigate the mid-term survival of large-diameter head total hip arthroplasty
patients operated on in three university hospitals and to compare these results
to the survival of hip resurfacing arthroplasty patients. MATERIAL AND METHODS: A
total of 3860 hip arthroplasties (3029 large-diameter head total hip
arthroplasties in 2734 patients and 831 hip resurfacing arthroplasties in 757
patients) were operated on between January 2004 and December 2009. The mean
follow-up was 4.3 years (range: 0.3-8.0 years) in the total hip arthroplasty
group and 5.1 years (range: 1.7-7.9 years) in the hip resurfacing arthroplasty
group. Cox multiple regression model and Kaplan-Meier survival analysis were used
to study the survival of the total hip arthroplasties and the hip resurfacing
arthroplasties. Intraoperative complications and reasons for revisions were also
evaluated. RESULTS: In Cox regression analysis, the hazard ratio for revision of
hip resurfacing arthroplasty was 1.5 compared with large-diameter head total hip
arthroplasty (95% confidence interval: 1.0-2.2) ( p = 0.029). The cumulative
Kaplan-Meier survival rate was 90.7% at 7.7 years for the large-diameter head
total hip arthroplasty (95% confidence interval: 86.8-94.6) and 92.2% at 7.6
years for hip resurfacing arthroplasty (95% confidence interval: 89.9-94.6).
There were a total of 166/3029 (5.5%) intraoperative complications in the large
diameter head total hip arthroplasty group and 20/831 (2.4%) in the hip
resurfacing arthroplasty group ( p = 0.001). Revision for any reason was
performed on 137/3029 (4.5%) of the arthroplasties in the large-diameter head
total hip arthroplasty group and 52/831 (6.3%) in the hip resurfacing
arthroplasty group ( p = 0.04). CONCLUSION: The mid-term survival of both of
these devices was poor, and revisions due to adverse reactions to metal debris
will most likely rise at longer follow-up. There were more intraoperative
complications in the large-diameter head total hip arthroplasty group than in the
hip resurfacing arthroplasty group.
PMID- 29333942
TI - SIX1 and DACH1 influence the proliferation and apoptosis of hepatocellular
carcinoma through regulating p53.
AB - ABSTRACTS This research aimed to explore effects of SIX1 and DACH1 on
hepatocellular carcinoma (HCC) cell proliferation, apoptosis and cell cycle.
Fifty paired hepatocellular carcinoma tissues were screened for differentially
expressed genes. SIX1 and DACH1 expressions were subjected to qRT-PCR and western
blot in tumor tissues and cells. The knockdown efficiency of siRNAs and
transfection efficiency of cDNAs and siRNAs were validated by qRT-PCR and western
blot as well. Then colony formation assay and flow cytometry were applied to
observe cell proliferation, cell apoptosis and cell cycle changes.
Immunofluorescence co-localization and immunoprecipitation were used to analyze
the interaction between proteins which was quantified using western blot. Effects
of SIX1 and DACH1 on tumor growth and their expressions in tumors were confirmed
in vitro in nude mice model. Results of these experiments showed that SIX1 was
overexpressed while DACH1 was suppressed in HCC tissues and cells. The
suppression of SIX1 and overexpression of DACH1 not only inhibited cell
proliferation, but also induced cell apoptosis and arrested cell cycle in G2/M
phase compared with control group. Results of immunofluorescence co-localization
suggested that SIX1, p53 and DACH1 were significantly overlapped.
Immunoprecipitation showed that DACH1 (marked with Flag tag) could pull down p53
and SIX1, but SIX1 (marked with His tag) could only pull down DACH1, which
indicated that an indirect regulation between SIX1 and p53. Validated with
western blot afterwards, DACH1 overexpression suppressed tumorigenesis in vivo by
up-regulating p53 expression while SIX1 overexpression accelerated tumor growth
by down-regulating p53 expression. Therefore, the decrease of SIX1 facilitated
the expression of DACH1, thus activated the expression of p53 and suppressed the
progression of HCC both in vitro and in vivo.
PMID- 29333943
TI - Cyber-Victimization of People With Chronic Conditions and Disabilities: A
Systematic Review of Scope and Impact.
AB - The victimization of individuals with chronic conditions or disabilities is
prevalent with severe impact at psychological and physiological levels. With the
increasing use of technology these experiences were further reshaped. This
systematic review aimed at scoping the experiences of cyber-victimization of
people living with chronic conditions or disabilities and examine the documented
impact on them. Following a four-stage search strategy in several databases
including MEDLINE, Embase, PsychINFO, CINAHL, Cochrane and snowballing of
references, a total of 2,922 studies were scanned and 10 studies were eventually
included. Quality assessment was done in two phases using tools specific to
observational studies and cyber-victimization research. A narrative synthesis of
reported results covered a total of 3,070 people. Sample size ranged between 42
and 823 participants, and the age range was 6-71 years with a majority of White
ethnic backgrounds. Most studies (n=9) were cross sectional. The prevalence range
of cyber-victimization was 2%-41.7% based on variable definitions, duration and
methods. Targeted conditions included physical impairments, intellectual
disabilities and specific chronic diseases. The most common documented impact was
psychological/psychiatric, mainly depression followed by anxiety and distress.
Somatic health complaints and self-harm were also reported. We concluded that
people with chronic conditions and disabilities were consistently at higher risk
of victimization with devastating health complications. Research gaps were
identified such as the need to address more conditions and acknowledge
differences between heterogeneous health conditions. Other recommendations
include allowing flexibility and accountability to patients/victims in research
design, education on victimization and health consequences, and improving primary
care.
PMID- 29333944
TI - MiR-155 Promotes Uveal Melanoma Cell Proliferation and Invasion by Regulating
NDFIP1 Expression.
AB - MicroRNAs refer to small RNA molecules that destroy the messenger RNA by binding
on them inhibiting the production of protein. However, the role of miR-155 in
uveal melanoma metastasis remains largely unknown. In this study, we found that
miR-155 was upregulated in both uveal melanoma cells and tissues. Transfection of
miR-155 mimic into uveal melanoma cells led to an increase in cell growth and
invasion; in contrast, inhibition of miR-155 resulted in opposite effects. Also,
we identified Nedd4-family interacting protein 1 as a direct target of miR-155,
and the expression of Nedd4-family interacting protein 1 was inhibited by miR
155. Furthermore, ectopic expression of Nedd4-family interacting protein 1
restored the effects of miR-155 on cell proliferation and invasion of uveal
melanoma cells. In conclusion, miR-155 acts as a tumor promotor in uveal melanoma
through increasing cell proliferation and invasion. Thus, miR-155 might serve as
a potential therapeutic target in patients with uveal melanoma.
PMID- 29333945
TI - Remarkable response with pembrolizumab plus albumin-bound paclitaxel in 2 cases
of HER2-positive metastatic breast cancer who have failed to multi-anti-HER2
targeted therapy.
AB - In clinical practice, one subgroup patients of breast cancer might have developed
resistance to multi-anti-HER2 targeted drugs(trastuzumab, lapatinib and/or T-DM1)
and can not benefit from the anti-HER2 targeted therapy continuously. We attempt
to change the next therapic way for these patients. Two patients with metastatic
breast cancer who have failed to multi-anti-HER2 targeted therapy were treated
with pembrolizumab (2 mg/Kg, day1) plus albumin-bound paclitaxel (125 mg/m2,
day1,8) every 3 weeks. CT evaluation and HER2 ECD test were performed every 2
cycles. Both of the two patients achieved remarkable response with Partial
Remission (PR), meanwhile serum HER2 ECD levels (the upper normal limit is 15
ng/ml) showed a remarkable decreases(compared to the base line decreases 75% and
60% respectively). The results indicate that regimen of pembrolizumab combination
with albumin-bound paclitaxel might produce response in patients with HER2
positive metastatic breast cancer who have failed to multi-anti-HER2 targeted
therapy.
PMID- 29333946
TI - Does inside passing contribute to the high incidence of groin injuries in soccer?
A biomechanical analysis.
AB - Groin injuries are common in soccer and often cause time-loss from training.
While groin injuries have been linked to full effort kicking, the role of inside
passing is unclear. Therefore, the purpose of this study was to investigate hip
joint kinematics and muscle force, stress and contraction velocity for adductor
longus and gracilis during inside passing. 3D kinematics of ten soccer players
(23.4 yrs; 77.5 kg; 1.81 m) were captured with a motion capture system inside a
Footbonaut. Muscle force and contraction velocity were determined with AnyBody
Modelling System. Gracilis muscle forces were 9% lower compared to adductor
longus (p = 0.005), but muscle stress was 183% higher in gracilis (p = 0.005).
Contraction velocity reveals eccentric contraction of gracilis in the last
quarter of the swing phase. Considering the combination of eccentric contraction,
high muscle stress and the repetitive nature of inside passing, gracilis
accumulates high loads in matches and training. These results indicate that the
high incidence of groin injuries in soccer could be linked to isolated pass
training. Practitioners need to be aware of the risk and refrain from sudden
increases in the amount of pass training. This gives the musculoskeletal system
time to adapt and might avoid career threatening injuries.
PMID- 29333948
TI - Adult-Perpetrated Animal Abuse: A Systematic Literature Review.
AB - Adults perpetrate the majority of animal abuse incidents yet clinicians are left
with very little evidence base to advance/enhance their practice. The purpose of
this systematic review is to synthesize and evaluate the current literature on
adult-perpetrated animal abuse and to identify the etiological factors related to
this type of offending. Twenty-three studies met the specific inclusion criteria
but most importantly, they examined the characteristics of adult perpetrators of
animal abuse. The findings from this review were demarcated by sample type: (1)
Participants were the perpetrators of the animal abuse or held offense-supportive
attitudes and (2) participants were victims of intimate partner violence
reporting incidents of animal abuse perpetrated by their partner. From the
perpetrator perspective, there were key developmental (i.e., maladaptive
parenting strategies), behavioral (such as varied offending behaviors), and
psychological (e.g., callousness, empathy deficits) factors highlighted in the
literature. Finally, in the context of intimate partner violence, findings
indicated that perpetrators abuse animals to control, coerce, intimidate, and/or
manipulate their victims (this effect is moderated by the victims' emotional
attachment to their pet). This review inherently underlines treatment targets
that could achieve greater clinical gains, but we also conclude that more
empirical and theoretical work is needed in order to set an agenda that
prioritizes future research and effective practice.
PMID- 29333949
TI - The "reading man" flap for reconstruction of large periorbital defects.
AB - PURPOSE: The "reading man" flap (RMF), a double advancement transposition
cutaneous flap named for its appearance, has been described in the reconstruction
of various circular skin defects, particularly in the malar region. We describe
two cases where this flap was used to reconstruct the lower eyelid/periorbital
region. METHODS: Two oculoplastic patients with lower eyelid basal cell
carcinomas underwent Mohs micrographic excision resulting in a large skin
defects. In both cases, reconstruction was performed using the RMF. RESULTS: At 6
months, both patients achieved good cosmetic results with no case of secondary
eyelid malposition. CONCLUSION: The RMF is a useful adjunct to the armamentarium
of the oculoplastic surgeon for the reconstruction of large periorbital defects.
PMID- 29333947
TI - Persistence of hepatitis B immune memory until 9-10 years of age following
hepatitis B vaccination at birth and DTaP-IPV-HB-PRP~T vaccination at 2, 4 and 6
months.
AB - OBJECTIVE: To evaluate the long-term persistence of anti-hepatitis B surface
(HBs) antibodies and the response to a HB challenge re-vaccination in children
who had received a primary series of DTaP-IPV-HB-PRP~T (HexaximTM) or DTaP-IPV
HB/PRP~T (Infanrix hexaTM). METHODS: Two cohorts of participants who had
previously received HB vaccine at birth followed by either DTaP-IPV-HB-PRP~T or
DTaP-IPV-HB/PRP~T co-administered with PCV7 at 2, 4, 6 months of age in a
randomized, Phase III, observer-blind study in Thailand, were followed up for
anti-HBs antibodies (geometric mean concentrations [GMCs] and seroprotection [SP]
rate [% of participants with a titer >=10 mIU/mL]) at 12-18 months of age and 9
10 years of age. A monovalent HB challenge re-vaccination was administered at 9
10 years of age and the anamnestic response was evaluated. RESULTS: Anti-HBs GMCs
and SP rates in the DTaP-IPV-HB-PRP~T and DTaP-IPV-HB/PRP~T groups were high and
similar post-primary vaccination series (2477 mIU/mL and 99.5% and 2442 mIU/mL
and 99.5%, respectively) and declined to a similar extent in each group at 12-18
months (154.5 mIU/mL and 90.8% and 162.3 mIU/mL and 96.5%, respectively).
Antibody levels further declined at 9-10 years of age (13.3 mIU/mL and 49.3% and
8.0 mIU/mL and 42.9%) and a strong anamnestic response occurred in each group
post-HB challenge re-vaccination (92.8% and 98.7%, respectively). CONCLUSION: The
kinetics of long-term anti-HBs antibody persistence were similar following a
primary series of DTaP-IPV-HB-PRP~T or DTaP-IPV-HB/PRP~T. The response to a
subsequent HB challenge re-vaccination was strong and similar in each group,
demonstrating persisting immune memory.
PMID- 29333950
TI - Willingness to pay for an Ebola vaccine during the 2014-2016 ebola outbreak in
West Africa: Results from a U.S. National sample.
AB - The 2014-2016 Ebola virus outbreak in West Africa led to advances in the
development of vaccines against Ebola. This study examined factors associated
with willingness to pay for an Ebola vaccine among a U.S. national sample during
the recent Ebola outbreak. From April 30-May 8, 2015, a national survey was
conducted using the GfK Group's KnowlegePanel(r). Main outcome measures included
willingness to pay at least $1; more than $50; and more than $100 for an Ebola
vaccine. Analyses were conducted using weighted multivariable logistic
regression. Among participants (N = 1,447), 583 (40.3%) would not pay for an
Ebola vaccine; 864 (59.7%) would pay at least $1. Among those willing to pay at
least $1: 570 (66.0%) would pay $1-50; 174 (20.1%) would pay $51-100; and 120
(13.9%) would pay more than $100. Willingness to pay at least $1 for an Ebola
vaccine was associated with international travel; interest in getting an Ebola
vaccine; and beliefs that the U.S. government should spend money to control Ebola
and assume worldwide leadership in confronting emerging epidemics. Willingness to
pay more than $50 was associated with similar variables. Willingness to pay more
than $100 was associated with international travel; interest in getting an Ebola
vaccine; information seeking; and beliefs that the U.S. government should assume
worldwide leadership in confronting emerging epidemics. International travel and
interest in an Ebola vaccine were key predictors of willingness to pay across all
price points. Understanding willingness to pay for vaccines against emerging
infectious diseases remains critical.
PMID- 29333951
TI - A Systematic Review of Risk and Protective Factors for Externalizing Problems in
Children Exposed to Intimate Partner Violence.
AB - Intimate partner violence (IPV) is a serious public health issue with innumerable
costs to the victims, children, and families affected as well as society at
large. The evidence is conclusive regarding a strong association between exposure
to IPV and children's externalizing problems. Moving forward, the next step is to
enhance our understanding of risk and protective factors associated with these
outcomes in order to tailor treatments to meet the needs of both parents and
children. The databases Medline, PubMed, and PsyINFO were searched combining
variations of the key words such as parent*, child*, mother, partner abuse,
domestic abuse, spousal abuse, interpersonal violence, domestic violence, or
intimate partner violence. This search were combined with child externalizing
behaviors specifically conduct*, oppositional defiant disorder, externaliz*,
aggress*, hyperactivity, and ADHD. A total of 31 studies from all three databases
were reviewed following application of inclusion and exclusion criteria. The main
findings were that child age and gender, callous-unemotional traits, cognitive
appraisals, maternal mental health, and quality of parenting emerged as key
mediating and moderating factors of the relationship between IPV exposure and
child externalizing problems. These findings suggest that interventions provided
to families exposed to IPV need to target both maternal and child risk factors in
order to successfully reduce child externalizing problems.
PMID- 29333952
TI - Trauma Intervention in Sub-Saharan African Children: A Systematic Literature
Review.
AB - Sub-Saharan Africa is a part of the world that is highly affected by a large
number of atrocities, causing a myriad of financial, physical health, and mental
health consequences. Yet, unfortunately, according to the World Health
Organization (WHO), this is also the part of the world that is least served by
mental health services. In response, the WHO has created mandates to increase
mental health resources and capacity in all countries. Researchers have taken on
the work of introducing and adapting treatments in various sub-Saharan African
countries with an aim to create sustainable, evidence-based treatment in a part
of the world with high need. The current qualitative systematic review of the
literature examines 20 articles that report on research conducted in sub-Saharan
African countries with children who have suffered different types of traumas.
This review answers questions concerning the types of treatments used, the people
administering the treatments, the measures they take to adapt these treatments,
and the types of outcomes that are seen. Overall, the majority of treatments
being used are shown to be effective with the associated populations.
PMID- 29333953
TI - The irreversible ERBB1/2/4 inhibitor neratinib interacts with the BCL-2 inhibitor
venetoclax to kill mammary cancer cells.
AB - The irreversible ERBB1/2/4 inhibitor, neratinib, down-regulates the expression of
ERBB1/2/4 as well as the levels of MCL-1 and BCL-XL. Venetoclax (ABT199) is a BCL
2 inhibitor. At physiologic concentrations neratinib interacted in a synergistic
fashion with venetoclax to kill HER2 + and TNBC mammary carcinoma cells. This was
associated with the drug-combination: reducing the expression and phosphorylation
of ERBB1/2/3; in an eIF2alpha-dependent fashion reducing the expression of MCL-1
and BCL-XL and increasing the expression of Beclin1 and ATG5; and increasing the
activity of the ATM-AMPKalpha-ULK1 S317 pathway which was causal in the formation
of toxic autophagosomes. Although knock down of BAX or BAK reduced drug
combination lethality, knock down of BAX and BAK did not prevent the drug
combination from increasing autophagosome and autolysosome formation. Knock down
of ATM, AMPKalpha, Beclin1 or over-expression of activated mTOR prevented the
induction of autophagy and in parallel suppressed tumor cell killing. Knock down
of ATM, AMPKalpha, Beclin1 or cathepsin B prevented the drug-induced activation
of BAX and BAK whereas knock down of BID was only partially inhibitory. A 3-day
transient exposure of established estrogen-independent HER2 + BT474 mammary
tumors to neratinib or venetoclax did not significantly alter tumor growth
whereas exposure to [neratinib + venetoclax] caused a significant 7-day
suppression of growth by day 19. The drug combination neither altered animal body
mass nor behavior. We conclude that venetoclax enhances neratinib lethality by
facilitating toxic BH3 domain protein activation via autophagy which enhances the
efficacy of neratinib to promote greater levels of cell killing.
PMID- 29333954
TI - Prevalence, Diagnosis, and Treatment Rates of Mood Disorders among Opioid Users
under Criminal Justice Supervision.
AB - BACKGROUND: Individuals involved in the criminal justice system have
disproportionately high rates of psychiatric disorders when compared to the
general U.S. POPULATION: If left untreated, the likelihood of subsequent arrest
increases and risk for adverse health consequences is great, particularly among
opioid users. OBJECTIVES: To explore the prevalence, characteristics, and
treatment of mood disorders among justice involved opioid-dependent populations.
METHODS: The current study enrolled 258 treatment-seeking opioid-dependent
individuals under community-based criminal justice supervision (e.g., probation,
parole) screened from the larger parent study, Project STRIDE, a seek/test/treat
randomized control trial (RCT) examining HIV and opioid use treatment. During
baseline, individuals were screened for depression using the Patient Health
Questionnaire-9 (PHQ-9) and screened for bipolar disorder using the Mood Disorder
Questionnaire (MDQ) tool. RESULTS: Overall, 78 (30%) participants screened
positive for moderate to severe depression and 54 (21%) screened positive for
bipolar disorder. Participants self-reported mood disorders at higher rates than
they screened positive for these conditions. Participants screening positive for
these conditions experienced significantly greater family, legal, and medical
problems on the Addiction Severity Index-Lite (ASI-Lite) than those who did not
screen positive. Incidence of a lifetime suicide attempt was found to be
associated with a positive screen for both mood disorders. Prescribed
psychotropic treatment utilization was similar among those who screened positive
for depression or bipolar disorder with approximately 38% reporting taking
medication. IMPORTANCE: Findings suggest universal mood disorder screening to
improve comprehensive psychiatric care and treatment of opioid-dependent justice
involved individuals.
PMID- 29333955
TI - The Relationship Between Internalized Homophobia and Intimate Partner Violence in
Same-Sex Relationships: A Meta-Analysis.
AB - A meta-analysis was conducted to investigate the association between internalized
homophobia and intimate partner violence (IPV) perpetration and victimization in
same-sex relationships. The literature search and the application of the
inclusion criteria made it possible to identify 10 studies, 2 of which were
excluded due to missing data. Therefore, eight studies were finally included in
the meta-analysis. The results showed positive and statistically significant
associations between internalized homophobia and IPV perpetration and
victimization, indicating that higher levels of internalized homophobia were
related to higher levels of IPV. Specifically, the pooled effect size for the
relationship between internalized homophobia and IPV perpetration (all forms), it
was r+ = .147, 95% confidence interval (CI) = [.079, .214]; for the association
between internalized homophobia and physical/sexual IPV perpetration, it was r+ =
.166, 95% CI [.109, .221]; p < .0001; for the relationship between internalized
homophobia and psychological IPV perpetration, it was r+ = .145, 95% CI [.073,
.216]; and for the association between internalized homophobia and any type of
IPV victimization, it was r+ = .102, 95% CI [.030, .173]. Implications of these
results for clinical practice and future research are discussed.
PMID- 29333956
TI - High-efficiency treatment of PTA wastewater using a biogas jet assisted anaerobic
fluidized bed reactor.
AB - In this paper, a new type of biogas jet assisted anaerobic fluidized bed reactor
loaded with a polypropylene carrier has been proposed. There was a clear
improvement in the fluidized state due to the biogas assisted input when the
gas/water ratio was set at 1:3 with a suitable carrier loading of 60%. When the
circulating water flow is 30 L/min assisted with biogas 10 L/min, the mixing time
shortens from 26 to 18 s. The performance of anaerobic biodegradation on
wastewater treatment was improved largely. The chemical oxygen demand (COD) and
terepthallic acid removal efficiencies were at 85.4% and 84%, respectively, at
hydraulic retention time of 20 h, even when the influent COD concentration was as
high as 4224 mg/L. In addition, plenty of microorganisms, attached to the
carriers and assumed to be the reason behind the organic biodegradation
efficiency of the proposed system, were observed using scanning electron
microscopy.
PMID- 29333957
TI - MiR-98 Promotes Apoptosis of Glioma Cells via Suppressing IKBKE/NF-kappaB
Pathway.
AB - The inhibitor of kappa B kinase epsilon is overexpressed in glioma and plays
antiapoptotic role via activating nuclear factor-kappa B. microRNA-98 can
suppress glioma, modulate the activities of nuclear factor-kappa B, and bind to
the 3'-untranslated region of inhibitor of kappa B kinase epsilon messenger RNA.
This study was aimed to investigate the modulation of inhibitor of kappa B kinase
epsilon/nuclear factor-kappa B by microRNA-98 in glioma. The results indicated
that microRNA-98 was downregulated in glioma cell lines and human glioma tissues.
Overexpression of microRNA-98 in U87MG and T98G glioma cells significantly
increased the apoptosis induced by ultraviolet irradiation and suppressed nuclear
factor-kappa B luciferase activity, nuclear factor-kappa B p50 subunit
expression, and B-cell lymphoma-2 (Bcl-2) expression in glioma cells. Silencing
inhibitor of kappa B kinase epsilon decreased the expression of nuclear factor
kappa B p50 subunit and the luciferase activity of nuclear factor-kappa B, while
the nuclear factor-kappa B activity could be significantly retrieved when
inhibitor of kappa B kinase epsilon was expressed in microRNA-98-transfected
cells. These findings indicated that microRNA-98 could promote apoptosis of
glioma cells via inhibiting inhibitor of kappa B kinase epsilon/nuclear factor
kappa B signaling and presented a novel regulatory pathway of microRNA-98 by
direct suppression of inhibitor of kappa B kinase epsilon/nuclear factor-kappa B
expression in glioma cells.
PMID- 29333958
TI - Focal MRI-Guided Salvage High-Dose-Rate Brachytherapy in Patients With
Radiorecurrent Prostate Cancer.
AB - INTRODUCTION: Whole-gland salvage treatment of radiorecurrent prostate cancer has
a high rate of severe toxicity. The standard of care in case of a biochemical
recurrence is androgen deprivation treatment, which is associated with morbidity
and negative effects on quality of life. A salvage treatment with acceptable
toxicity might postpone the start of androgen deprivation treatment, might have a
positive influence on the patients' quality of life, and might even be curative.
Here, toxicity and biochemical outcome are described after magnetic resonance
imaging-guided focal salvage high-dose-rate brachytherapy in patients with
radiorecurrent prostate cancer. MATERIALS AND METHODS: Seventeen patients with
pathologically proven locally recurrent prostate cancer were treated with focal
high-dose-rate brachytherapy in a single 19-Gy fraction using magnetic resonance
imaging for treatment guidance. Primary radiotherapy consisted of external beam
radiotherapy or low-dose-rate brachytherapy. Tumors were delineated with Ga-68
prostate-specific membrane antigen or F18-choline positron emission tomography in
combination with multiparametric magnetic resonance imaging. All patients had a
prostate-specific antigen level of less than 10 ng/mL at the time of recurrence
and a prostate-specific antigen doubling time of >=12 months. Toxicity was
measured by using the Common Terminology Criteria for Adverse Events version 4.
RESULTS: Eight of 17 patients had follow-up interval of at least 1 year. At a
median follow-up interval of 10 months (range 3-40 months), 1 patient experienced
a biochemical recurrence according to the Phoenix criteria, and prostate-specific
membrane antigen testing revealed that this was due to a distant nodal
metastasis. One patient had a grade 3 urethral stricture at 2 years after
treatment. CONCLUSION: Focal salvage high-dose-rate brachytherapy in patients
with radiorecurrent prostate cancer showed grade 3 toxicity in 1 of 17 patients
and a distant nodal metastasis in another patient. Whether this treatment option
leads to cure in a subset of patients or whether it can successfully postpone
androgen deprivation treatment needs further investigation.
PMID- 29333960
TI - A Meta-Analysis of Risk and Protective Factors for Dating Violence Victimization:
The Role of Family and Peer Interpersonal Context.
AB - Dating violence (DV) is a widespread social issue that has numerous deleterious
repercussions on youths' health. Family and peer risk factors for DV have been
widely studied, but with inconsistent methodologies, which complicates global
comprehension of the phenomenon. Protective factors, although understudied,
constitutes a promising line of research for prevention. To date, there is no
comprehensive quantitative review attempting to summarize knowledge on both
family and peer factors that increase or decrease the risk for adolescents and
emerging adults DV victimization. The current meta-analysis draws on 87 studies
with a total sample of 278,712 adolescents and young adults to examine effect
sizes of the association between various family and peer correlates of DV
victimization. Results suggest small, significant effect sizes for all the family
(various forms of child maltreatment, parental support, and parental monitoring)
and peer factors (peer victimization, sexual harassment, affiliation with deviant
peers, and supportive/prosocial peers) in the prediction of DV. With few
exceptions, forms of DV (psychological, physical, and sexual), gender, and age
did not moderate the strength of these associations. In addition, no difference
was found between the magnitude of family and peer factors' effect sizes,
suggesting that these determinants are equally important in predicting DV. The
current results provide future directions for examining relations between risk
and protective factors for DV and indicate that both peers and family should be
part of the development of efficient prevention options.
PMID- 29333959
TI - A Noninvasive Body Setup Method for Radiotherapy by Using a Multimodal Image
Fusion Technique.
AB - PURPOSE: To minimize the mismatch error between patient surface and
immobilization system for tumor location by a noninvasive patient setup method.
MATERIALS AND METHODS: The method, based on a point set registration, proposes a
shift for patient positioning by integrating information of the computed
tomography scans and that of optical surface landmarks. An evaluation of the
method included 3 areas: (1) a validation on a phantom by estimating 100 known
mismatch errors between patient surface and immobilization system. (2) Five
patients with pelvic tumors were considered. The tumor location errors of the
method were measured using the difference between the proposal shift of cone-beam
computed tomography and that of our method. (3) The collected setup data from the
evaluation of patients were compared with the published performance data of other
2 similar systems. RESULTS: The phantom verification results showed that the
method was capable of estimating mismatch error between patient surface and
immobilization system in a precision of <0.22 mm. For the pelvic tumor, the
method had an average tumor location error of 1.303, 2.602, and 1.684 mm in left
right, anterior-posterior, and superior-inferior directions, respectively. The
performance comparison with other 2 similar systems suggested that the method had
a better positioning accuracy for pelvic tumor location. CONCLUSION: By
effectively decreasing an interfraction uncertainty source (mismatch error
between patient surface and immobilization system) in radiotherapy, the method
can improve patient positioning precision for pelvic tumor.
PMID- 29333961
TI - Helping Survivors of Human Trafficking: A Systematic Review of Exit and Postexit
Interventions.
AB - BACKGROUND: Human trafficking is a global problem and results in deleterious
psychological, social, and physical effects on the lives of those who are
trafficked; however, it is not clear how to best intervene with survivors. The
purpose of this review was to synthesize the evidence of exit and postexit
intervention programs for survivors of human trafficking to inform practice and
research. METHOD: Systematic review methods were used to search, select, and
extract data from published and unpublished experimental, quasi-experimental, and
preexperimental studies that assessed the effects of any exit or postexit
interventions for victims of human trafficking. The authors searched eight
databases, reviewed bibliographies, and conducted forward citation searches from
relevant reports and prior reviews to find studies authored between 2005 and
2015. RESULTS: The search yielded six eligible studies that included 155 female
and 6 male survivors from four countries. Interventions were diverse, with three
using a trauma-informed approach. Authors measured a myriad of outcomes,
including mental health, social network, community reintegration, and employment;
however, the quality of most studies was poor. DISCUSSION: Evidence of effects of
exit and postexit interventions is sparse, and much of the research is poorly
designed and executed; however, the needs of trafficking survivors are complex
and effective interventions are desperately needed. Implications for practice and
research are discussed.
PMID- 29333962
TI - Childhood Maltreatment and the Risk for Criminal Justice Involvement and
Victimization Among Homeless Individuals: A Systematic Review.
AB - Homeless individuals are at higher risk of criminal justice involvement (CJI) and
victimization compared to their housed counterparts. Exposure to childhood
maltreatment (CM; e.g., abuse, neglect) is one of the most significant predictors
of CJI and victimization among homeless populations. The aim of this systematic
review was to synthesize current knowledge regarding the relationship between CM
and CJI and victimization among homeless individuals. Guided by the preferred
reporting items for systematic reviews and meta-analyses (PRISMA) methods, a
systematic search was performed using PsycINFO, MEDLINE, Embase, Web of Science,
and the Cumulative Index to Nursing and Allied Health Literature for published
studies investigating the relationship between CM and CJI and victimization among
homeless samples. We identified 20 studies that met the inclusion criteria.
Findings showed that across the majority of studies, CM, and in particular
childhood physical (CPA) and sexual (CSA) abuse, is associated with increased
risk of both CJI and victimization, regardless of various important factors
(e.g., sociodemographic characteristics, psychiatric disorders, substance use).
These findings support the need for prevention and treatment for "families at
risk" (i.e., for intimate partner violence, child abuse and neglect) and also
document the need for trauma-informed approaches within services for homeless
individuals. Future research should focus on prospective designs that examine
victimization and CJI in the same samples.
PMID- 29333963
TI - The Differential Victimization Associated With Depression and Anxiety in Cross
Cultural Perspective: A Meta-Analysis.
AB - Traditional bullying and cyberbullying have become serious worldwide issues. The
meta-analysis in this article took a cross-cultural perspective to explore
whether there were any differences between the effects of cyber victimization and
traditional victimization on the presence of depression and anxiety in children
and adolescents and to examine the effects of moderators in explaining these
differences/similarities. Fifty-six empirical studies (generating 148 independent
samples) were included with a total sample size of 214,819 participants. The
results indicated that the effects of cyber victimization and the subtypes of
traditional victimization on anxiety were significantly different, and there was
a marginally significant difference for depression. The moderating effects of
country of origin were found to be significant for depression, with the mean
effect size in North America being significantly higher than in China and Europe,
which suggested that culture was an important factor. The moderating effects of
age were also found to be significant for the relationships between traditional
victimization and depression, traditional victimization and anxiety, cyber
victimization and depression, and cyber victimization and anxiety. In addition,
the effect size for cyber victimization and depression has increased in more
recent publication years.
PMID- 29333964
TI - The Scale of Sexual Aggression in Southeast Asia: A Review.
AB - Southeast Asia is one of the most dynamic regions in the world. It is
experiencing rapid socioeconomic change that may influence the level of sexual
aggression, but data on the scale of sexual aggression in the region remain
sparse. The aim of the present article was to systematically review the findings
of studies available in English on the prevalence of self-reported sexual
aggression and victimization among women and men above the age of 12 years in the
11 countries of Southeast Asia (Brunei, Cambodia, East Timor, Indonesia, Laos,
Malaysia, Myanmar, the Philippines, Singapore, Thailand, and Vietnam). Based on
four scientific databases, the search engine Google, Opengrey database, and
reference checking, 49 studies were found on sexual victimization. Of those, 32
included only women. Self-reported perpetration was assessed by only three
studies and included all-male samples. Prevalence rates varied widely across
studies but showed that sexual victimization was widespread among different
social groups, irrespective of sex and sexual orientation. Methodological
heterogeneity, lack of representativeness of samples, imbalance of information
available by country, missing information within studies, and cultural
differences hampered the comparability between and within countries. There is a
need for operationalizations that specifically address sexual aggression
occurring after the age of consent, based on detailed behavioral descriptions of
unwanted sexual experiences and allied to a qualitative approach with cultural
sensitivity. Data on sexual aggression in conflict settings and in human
trafficking are also limited. Recommendations for future research are presented
in the discussion.
PMID- 29333965
TI - Prevalence of Sexual Aggression Victimization and Perpetration in Chile: A
Systematic Review.
AB - Sexual aggression is a major public health issue worldwide, but most knowledge is
derived from studies conducted in North America and Western Europe. Little
research has been conducted on the prevalence of sexual aggression in developing
countries, including Chile. This article presents the first systematic review of
the evidence on the prevalence of sexual aggression victimization and
perpetration among women and men in Chile. Furthermore, it reports differences in
prevalence rates in relation to victim and perpetrator characteristics and victim
perpetrator relationships. A total of N = 28 studies were identified by a three
stage literature search, including the screening of academic databases,
publications of Chilean institutions, and reference lists. A great heterogeneity
was found for prevalence rates of sexual victimization, ranging between 1.0% and
51.9% for women and 0.4% and 48.0% for men. Only four studies provided
perpetration rates, which varied between 0.8% and 26.8% for men and 0.0% and
16.5% for women. No consistent evidence emerged for differences in victimization
rates in relation to victims' gender, age, and education. Perpetrators were more
likely to be persons known to the victim. Conceptual and methodological
differences between the studies are discussed as reasons for the great
variability in prevalence rates, and recommendations are provided for a more
harmonized and gender-inclusive approach for future research on sexual aggression
in Chile.
PMID- 29333966
TI - The Impacts of Sexual Media Exposure on Adolescent and Emerging Adults' Dating
and Sexual Violence Attitudes and Behaviors: A Critical Review of the Literature.
AB - Dating violence (DV) and sexual violence (SV) are widespread problems among
adolescents and emerging adults. A growing body of literature demonstrates that
exposure to sexually explicit media (SEM) and sexually violent media (SVM) may be
risk factors for DV and SV. The purpose of this article is to provide a
systematic and comprehensive literature review on the impact of exposure to SEM
and SVM on DV and SV attitudes and behaviors. A total of 43 studies utilizing
adolescent and emerging adult samples were reviewed, and collectively the
findings suggest that (1) exposure to SEM and SVM is positively related to DV and
SV myths and more accepting attitudes toward DV and SV; (2) exposure to SEM and
SVM is positively related to actual and anticipated DV and SV victimization,
perpetration, and bystander nonintervention; (3) SEM and SVM more strongly impact
men's DV and SV attitudes and behaviors than women's DV and SV attitudes and
behaviors; and (4) preexisting attitudes related to DV and SV and media
preferences moderate the relationship between SEM and SVM exposure and DV and SV
attitudes and behaviors. Future studies should strive to employ longitudinal and
experimental designs, more closely examine the mediators and moderators of SEM
and SVM exposure on DV and SV outcomes, focus on the impacts of SEM and SVM that
extend beyond men's use of violence against women, and examine the extent to
which media literacy programs could be used independently or in conjunction with
existing DV and SV prevention programs to enhance effectiveness of these
programming efforts.
PMID- 29333967
TI - A Meta-Analysis of Risk Markers for Intimate Partner Violence in Same-Sex
Relationships.
AB - Research on intimate partner violence (IPV) has largely focused on heterosexual
relationships, but, in recent years, researchers have expanded their focus to
include same-sex relationships. Using meta-analytic techniques, this study was
conducted to examine the relative strength of various risk markers for men and
women being perpetrators and victims of physical IPV in same-sex relationships.
Articles were identified through research search engines and screened to identify
articles fitting the inclusion criteria, a process that resulted in 24 studies
and 114 effect sizes for the meta-analysis. The strongest risk marker among those
with at least two effect sizes for both male and female perpetration was
psychological abuse perpetration. The strongest risk marker among those with at
least two effect sizes for IPV victimization was also perpetration of
psychological abuse for males and psychological abuse victimization for females.
Among same-sex-specific risk markers, internalized homophobia and fusion were the
strongest predictors for being perpetrators of IPV for men and women,
respectively. HIV status and internalized homophobia were the strongest risk
markers for IPV victimization for men and women, respectively. Of 10 comparisons
between men and women in risk markers for IPV perpetration and victimization,
only 1 significant difference was found. The results suggest that although same
sex and heterosexual relationships may share a number of risk markers for IPV,
there are risk markers for physical IPV unique to same-sex relationships. Further
research and increased specificity in measurement are needed to better study and
understand the influence of same-sex-specific risk markers for IPV.
PMID- 29333968
TI - The Complexity of Adaptation to Childhood Polyvictimization in Youth and Young
Adults: Recommendations for Multidisciplinary Responders.
AB - Exposure to violence is pervasive in our society. An abundance of research has
demonstrated that individuals who experience polyvictimization (PV)-prolonged or
multiple forms of traumatic victimizations-are at heightened risk for continuing
to experience repeated victimizations throughout their lifetimes. The current
article reviews several overlapping constructs of traumatic victimizations with
the ultimate goal of providing a unifying framework for conceptualizing prolonged
and multiple victimization (defined in this article as PV) as a precursor to
complex post-traumatic biopsychosocial adaptations, revictimization, and in some
instances reenactment as a perpetrator (defined as complex trauma [CT]). This
model is then applied to three socially disadvantaged victim populations-lesbian,
gay, bisexual, transgender, queer, or questioning; commercially sexually
exploited individuals; and urban communities of color-who are at heightened risk
for PV and for exhibiting complex clinical presentations to demonstrate how the
PV-CT framework can destigmatize, reframe, and ultimately reduce health
disparities experienced by these populations. Trauma-informed recommendations are
provided to aid researchers and multidisciplinary providers working to reduce
harm and improve the quality of life for polyvictims.
PMID- 29333969
TI - Sexual Violence Against Older People: A Review of the Empirical Literature.
AB - Aging and sexual violence are both established areas of research, but little
attention has been paid to research into sexual violence against older people.
This article presents a critical review of the literature reporting empirical
research in three overlapping fields of inquiry: elder abuse, domestic violence,
and sexual violence, identifying points of theoretical and methodological
similarity and difference across academic disciplines. Using a range of search
terms combining age, sexual violence, and elder abuse, the following databases
were searched: EBSCOHOST, Ingenta-Ingenta connect, and JSTOR. In total, the
databases searches returned 31 relevant articles and an additional 9 relevant
articles were found through manual searches of bibliographies and Google
searches, which were grouped into three categories: elder abuse, domestic
violence in later life, and sexual violence against older people. Four themes
common across these fields emerged: prevalence, characteristics of victims and
risk factors, impacts and coping strategies, and perpetrator and assault
characteristics. The findings in each area are discussed in detail, exposing gaps
in knowledge and understandings of sexual violence against older women. The
article ends by defining a future research agenda for this underexplored
phenomenon that is of increasing importance in a context of global aging.
PMID- 29333970
TI - Parental Migration, Children's Safety and Psychological Adjustment in Rural
China: A Meta-Analysis.
AB - Studies concerning left-behind children in rural China have shown that parental
absence due to migration is associated with greater risk of child victimization
and accidental injuries, and a range of psychosocial problems. The authors
conducted this meta-analysis to determine the extent to which left-behind
children are affected by parental migration, as compared to children in
nonmigrant rural families. A comprehensive literature search was conducted, and
90 studies published before 2017 were included in the data synthesis and
analysis. The results revealed that compared to non-left-behind children, rural
left-behind children are generally more disadvantaged in regard to child safety (
d = 0.27) and psychological adjustment ( d = 0.25). The effect sizes, though
interpreted as small, revealed that children in rural China are significantly
affected by parental migration. Children's educational stage was a significant
variable that moderated the effect sizes of child safety and psychological
adjustment. The findings of the meta-analysis indicated that mother-only
migration may have the most harmful effect on children. In terms of implications
for interventions, the results suggest more attention should be given to rural
left-behind children and to "mother-absent children" in particular. Future
research is warranted to explore the association between left-behind children's
psychological adjustment and their exposure to injury and victimization.
PMID- 29333971
TI - Using Photovoice to Address Gender-Based Violence: A Qualitative Systematic
Review.
AB - The purpose of this article is to examine how photovoice research addresses
gender-based violence (GBV) among individuals and communities that experience and
witness GBV. Photovoice action research (PVAR) methods act as both an
intervention and a research method by engaging participants in using photography
to depict a topic of concern and in developing potential solutions. To date,
there is not a published review of PVAR publications that focus on addressing
GBV. This article is comprised of a qualitative systematic review of studies that
use photovoice research methods to address GBV. This review is conducted in
accordance with the Supplementary Guidance of the Cochrane handbook and results
in the examination of 17 publications that meet inclusion criteria. The data
synthesis engages grounded theory (GT) methods and results in the emergence of
one primary category transgressing the violence and three subcategories
illustrating the problem, caring for self and others, and harnessing community
resources. The results of this review reveal research, practice, and policy
implications for photovoice projects aimed at addressing GBV.
PMID- 29333972
TI - Interventions in Health Settings for Male Perpetrators or Victims of Intimate
Partner Violence.
AB - BACKGROUND: Intimate partner violence (IPV) is common in patients attending
health-care services and is associated with a range of health problems. The
majority of IPV perpetrators are men, and a substantial minority of men are
victims, yet health-care professionals have little evidence or guidance on how to
respond to male patients who perpetrate or experience violence in their intimate
relationships. METHODS: We conducted a systematic review to determine the
effectiveness of interventions for male perpetrators or victims of IPV in health
settings. Online databases, reference lists, Google Scholar, and gray literature
were searched, and inclusion/exclusion criteria were applied. Narrative synthesis
methods were used due to the heterogeneity of study types and outcome measures.
RESULTS: Fourteen studies describing 10 interventions met our inclusion criteria:
nine randomized controlled trials, four cohort studies, and one case-control
study. Interventions were predominantly therapeutic in nature and many were
conducted in alcohol treatment settings. CONCLUSION: Overall, the evidence for
effectiveness of interventions in health-care settings was weak, although IPV
interventions conducted concurrently with alcohol treatment show some promise.
More work is urgently needed in health-care services to determine what
interventions might be effective, and in what settings, to improve the response
to male perpetrators or victims of IPV.
PMID- 29333973
TI - Facilitators and Barriers to Child Sexual Abuse (CSA) Disclosures: A Research
Update (2000-2016).
AB - Identifying and understanding factors that promote or inhibit child sexual abuse
(CSA) disclosures has the potential to facilitate earlier disclosures, assist
survivors to receive services without delay, and prevent further sexual
victimization. Timely access to therapeutic services can mitigate risk to the
mental health of survivors of all ages. This review of the research focuses on
CSA disclosures with children, youth, and adults across the life course. Using
Kiteley and Stogdon's literature review framework, 33 studies since 2000 were
identified and analyzed to extrapolate the most convincing findings to be
considered for practice and future research. The centering question asked: What
is the state of CSA disclosure research and what can be learned to apply to
practice and future research? Using Braun and Clarke's guidelines for thematic
analysis, five themes emerged: (1) Disclosure is an iterative, interactive
process rather than a discrete event best done within a relational context; (2)
contemporary disclosure models reflect a social-ecological, person-in-environment
orientation for understanding the complex interplay of individual, familial,
contextual, and cultural factors involved in CSA disclosure; (3) age and gender
significantly influence disclosure; (4) there is a lack of a life-course
perspective; and (5) barriers to disclosure continue to outweigh facilitators.
Although solid strides have been made in understanding CSA disclosures, the
current state of knowledge does not fully capture a cohesive picture of
disclosure processes and pathways over the life course. More research is needed
on environmental, contextual, and cultural factors. Barriers continue to be
identified more frequently than facilitators, although dialogical forums are
emerging as important facilitators of CSA disclosure. Implications for practice
in facilitating CSA disclosures are discussed with recommendations for future
research.
PMID- 29333974
TI - Understanding the Relation Between Neighborhoods and Intimate Partner Violence:
An Integrative Review.
AB - Stemming in part from the lack of theory, predictors of the relationship between
neighborhoods and intimate partner violence (IPV) are underidentified.
Furthermore, few mediation studies exist that inductively build and deductively
confirm theoretical frameworks. This article provides an integrative review of
the literature, aiming to enhance the field's understanding of predictors and
potential mechanisms that drive this relationship, using a combined theoretical
model to guide the analysis. The integrative review was conducted using
Whittemore and Knafl's systematic method for integrative reviews with articles
published between 1995 and 2015. Findings indicate that macro-, exo-, and
mesolevel predictors and mediators in the proposed model have modest empirical
support; however, a number of concepts at each ecological level have yet to be
fully researched. Results of this review suggest that a well-defined and
integrative theoretical framework will enhance the current understanding of
ecological research into IPV. Additionally, a comprehensive ecological approach
to IPV intervention is likely to be more effective than employing solely an
individual-level approach. Intervention implications are discussed.
PMID- 29333975
TI - Toward a Better Understanding of Psychological Symptoms in People Confronted With
the Disappearance of a Loved One: A Systematic Review.
AB - OBJECTIVE: The disappearance of a loved one is claimed to be the most stressful
type of loss. The present review explores the empirical evidence relating to this
claim. Specifically, it summarizes studies exploring the prevalence and
correlates of psychological symptoms in relatives of missing persons as well as
studies comparing levels of psychopathology in relatives of the disappeared and
the deceased. METHOD: Two independent reviewers performed a systematic search in
PsychINFO, Web of Science, and Medline, which resulted in 15 studies meeting
predefined inclusion criteria. Eligible studies included quantitative peer
reviewed articles and dissertations that assessed psychopathology in relatives of
missing person. RESULTS: All reviewed studies were focused on disappearances due
to war or state terrorism. Prevalence rates of psychopathology were mainly
described in terms of post-traumatic stress disorder and depression and varied
considerably among the studies. Number of experienced traumatic events and
kinship to the missing person were identified as correlates of psychopathology.
Comparative studies showed that psychopathology levels did not differ between
relatives of missing and deceased persons. CONCLUSIONS: The small number of
studies and the heterogeneity of the studies limit the understanding of
psychopathology in those left behind. More knowledge about psychopathology
postdisappearance could be gained by expanding the focus of research beyond
disappearances due to war or state terrorism.
PMID- 29333976
TI - Psychological Trauma in the Context of Familial Relationships: A Concept
Analysis.
AB - Many forms of psychological trauma are known to develop interpersonally within
important relationships, particularly familial. Within the varying theoretical
constructs of psychological traumas, and distinct from the processes of
diagnosis, there is a need to refine the scope and definitions of psychological
traumas that occur within important familial relationships to ensure a cohesive
evidence base and fidelity of the concept in application to practice. This review
used a philosophical inquiry methodology of concept analysis to identify the
definitions, antecedents, characteristics, and consequences of the varying
conceptualizations of psychological trauma occurring within important
relationships. Interactions between concepts of interpersonal trauma, relational
trauma, betrayal trauma, attachment trauma, developmental trauma, complex trauma,
cumulative trauma, and intergenerational trauma are presented. Understanding of
the discrete forms and pathways of transmission of psychological trauma between
individuals, including transgenerationally within families, creates opportunities
for prevention and early intervention within trauma-focused practice. This review
found that concepts of psychological trauma occurring within familial
relationships are not exclusive of each other but overlap in their encompassment
of events and circumstances as well as the effect on individuals of events in the
short term and long term. These traumas develop and are transmitted in the space
between people, both purposefully and incidentally, and have particularly
profound effects when they involve a dependent infant or child. Linguistic and
conceptual clarity is paramount for trauma research and practice.
PMID- 29333977
TI - The Prevalence of Self-Reported Elder Abuse Among Older Women in Community
Settings: A Systematic Review and Meta-Analysis.
AB - The abuse of older women appears to be a significant problem. Developing a better
understanding of the extent of the problem is an important step toward preventing
it. We conducted a global systematic review and meta-analysis of existing
prevalence studies, in multiple languages, that occurred in the community
settings from inception to June 26, 2015, in order to determine the extent of
abuse against women aged 60 years and over. To disentangle the wide variations in
prevalence estimates, we also investigated the associations between prevalence
estimates and studies' demographic and methodological characteristics. A total of
50 studies were included in the meta-analysis. The combined prevalence for
overall elder abuse in the past year was 14.1% (95% confidence interval (CI)
[11.0, 18.0]). Pooled prevalence for psychological abuse was 11.8% (95% CI [9.2%,
14.9%]), neglect was 4.1% (95% CI [2.7%, 6.3%]), financial abuse was 3.8% (95% CI
[2.5%, 5.5%]), sexual abuse was 2.2% (95% CI [1.6%, 3.0%]), and physical abuse
was 1.9% (95% CI [1.2%, 3.1%]). The studies included in the meta-analysis for
overall abuse were heterogeneous indicating that significant differences among
the prevalence estimates exist. Significant associations were found between
prevalence estimates and the following covariates: World Health Organization
defined regions, countries' income classification, and sample size. Together,
these covariates explained 37% of the variance. Although robust prevalence
studies are sparse in low- and middle-income countries, about 1 in 6, or 68
million older women experience abuse worldwide. More work is needed to understand
the variation in prevalence rates and implications for prevention.
PMID- 29333978
TI - The Prevalence of Domestic Violence Among Pregnant Women in Nigeria: A Systematic
Review.
AB - OBJECTIVE: To identify, appraise, and synthesize research evidence on the
prevalence of domestic violence (DV) among pregnant women in Nigeria. METHOD: We
conducted a systematic review of all published studies between April 2004 and
June 2016. Comprehensive searches were conducted on electronic databases such as
PubMed, CINAHL, Global Health, MEDLINE, PsycINFO, Directory of Open Access
Journals, Google Scholar, and electronic libraries of the authors' institution.
Identified articles were screened in two stages against the inclusion criteria
with titles and abstract screened first followed by full-text screening. Selected
articles were assessed using the "guidelines for evaluating prevalence studies,"
and findings were synthesized narratively. RESULTS: Among 19 studies that met the
inclusion criteria, two articles were excluded due to low methodological quality
and 17 articles were included in the review. The prevalence of DV during
pregnancy in Nigeria ranged between 2.3% and 44.6% with lifetime prevalence rates
ranging between 33.1% and 63.2%. Physical, sexual, psychological, and verbal
abuses were the most frequent types of DV reported in this review. The most
common perpetrators were husbands, as reported in 11 of the 17 studies. Pregnant
women between the ages of 20 and 30 years were the most common victims of DV.
CONCLUSION: Our review suggests high prevalence of DV in pregnancy among women in
Nigeria and higher lifetime prevalence. However, determining an overall,
synthesized accurate prevalence rate of DV within this population based on
existing evidence presents a challenge. The findings have important implications
for stakeholders such as planners, policy makers, maternity care providers, and
researchers in public health and social policy at national, regional, and
international levels toward combating the issue.
PMID- 29333979
TI - Effect of anoxic to aerobic duration ratios on nitrogen removal and nitrous oxide
emission in the multiple anoxic/aerobic process.
AB - Characteristics of nitrogen removal and nitrous oxide (N2O) emission in the
multiple anoxic/aerobic (AO) process were examined in three sequencing batch
reactors (SBRs) with different anoxic durations (50 min, SBRH; 40 min, SBRM; 30
min, SBRL) and a fixed aerobic duration of 30 min. The highest total inorganic
nitrogen removal percentage of 85.8% was obtained in SBRH, while a minimum N2O
emission factor of 1.9% was obtained in SBRL. During nitrification batch
experiments, the N2O emission factor and emission rate were both lower in SBRH
than SBRL. More N2O production was obtained during denitrification in SBRH when
denitrifiers utilized intracellular organic carbon. Nitrite reduction by
heterotrophs was the main N2O production pathway during simultaneous
nitrification and denitrification in SBRH and SBRL, with the N2O emission factor
of 31.3% and 36.3%, respectively. Adequate anoxic duration and lowering aerobic
nitrite concentrations could be adopted to mitigate N2O emission in the multiple
AO process. The dominant microorganisms at the phylum level in all reactors were
Proteobacteria and Bacteroidetes, while the abundance of Nitrospira was the
highest in SBRH with relatively lowest dissolved oxygen concentrations.
PMID- 29333981
TI - Co-Occurring Substance Use, PTSD, and IPV Victimization: Implications for Female
Offender Services.
AB - The co-occurrence of substance use disorders (SUDs) and post-traumatic stress
disorder (PTSD) among women who have been the victims of intimate partner
violence (IPV) is complex and causal associations cannot be assumed. Although the
presence of co-occurring disorders among IPV victims is a well-established
research finding, there is a need for improved understanding of their prevalence
and related mental health treatment requirements among female offenders. We
review research indicating that service providers working with IPV victims can
expect to encounter women with extensive concurrent problems and examine evidence
for integrated treatment for SUD, PTSD, and IPV. We propose an outline for
assessing and treating SUD and PTSD among female offenders who have experienced
IPV victimization. We intend this review to build on previous calls in the co
occurring disorders literature and help integrate the research and treatment
evaluation literatures in a way that points to practical implications for policy
and practice in female offender services.
PMID- 29333980
TI - Percentages of PD-1+CD4+T cells and PD-L1+DCs are increased and sPD-1 level is
elevated in patients with immune thrombocytopenia.
AB - The present study is to measure the expression of programmed death (PD)-1 /
programmed death ligand-1 (PD-L1) negative costimulatory molecules, soluble
format sPD-1 in patients with immune thrombocytopenia (ITP), and to investigate
their correlation with the secretion of cytokines. A total of 35 patients with
ITP were included in the present study. Twenty healthy subjects who received
physical examination at our hospital were included as control group. Peripheral
blood was collected from all ITP patients and healthy subjects. Flow cytometry
was performed to determine the percentages of PD-1+CD4+T cells and PD-L1+DCs in
ITP patients and healthy subjects. Enzyme-linked immunosorbent assay was
performed to measure the concentrations of interferon (IFN)-gamma, interleukin
(IL)-17 and sPD-1 in peripheral blood from ITP patients and healthy subjects.
Percentages of PD-1+CD4+T cells and PD-L1+DCs in peripheral blood from ITP
patients before treatment were significantly higher than that from healthy
subjects, but were not different from those after treatment. Serum concentrations
of IFN-gamma, IL-17 and sPD-1 in ITP patients before treatment were significantly
higher than those in healthy subjects, and these concentrations were
significantly reduced after treatment. The concentration of sPD-1 was positively
correlated with the concentration of IFN-gamma, and negatively correlated with
platelet count. Percentages of PD-1+CD4+T cells and PD-L1+DCs in ITP patients are
higher than those in healthy subjects, but elevated sPD-1 concentration in the
blood blocks PD-1/PD-L1 signaling pathway, leading to unaffected Th cell
function. Elevated concentrations of IFN-gamma and IL-17 in the blood may
participate in the occurrence and development of ITP.
PMID- 29333982
TI - Violence Against Young Women in Non-urban Areas of Australia: A Scoping Review.
AB - Violence against women is globally prevalent and harmful to women's health and
well-being. Younger women are at higher risk of abuse, especially those from non
urban areas who may face specific barriers to disclosure and support. The aim of
this review was to map the breadth and nature of the "violence against women"
literature particular to young non-urban Australian women and identify research
gaps to inform future research with young people. A comprehensive scoping review
methodology, as outlined by Arksey and O'Malley, was adopted. English language,
peer-reviewed articles were identified from five databases between January 2000
and July 2015. Grey literature was also examined. Inclusion criteria for the
review included young women (15-24 years) from non-urban areas of Australia.
Twenty-four full-text articles were included in this review. Themes identified
include prevalence and type of abuse, experiences and response to violence, and
the consequences of abuse. Recommendations from the review which are relevant to
a global audience include the need for improved service access, improved data
collection on the prevalence of violence, and a focus on more research with young
women in non-urban areas. There is limited research on violence against young
women living in non-urban areas of Australia. Evidence to date consists of
predominantly quantitative data generated from general population surveys. There
is a lack of qualitative research on this topic, and we argue that more is needed
to gain a better understanding of the violence that young women experience.
PMID- 29333983
TI - Intimate Partner Violence in Male Survivors of Child Maltreatment: A Meta
Analysis.
AB - Intimate partner violence (IPV) is a major public health concern. Yet, despite an
increasingly extensive literature on interpersonal violence, research on male
victims of IPV remains sparse and the associations between different forms of
child maltreatment (CM) and IPV victimization and perpetration in men remains
unclear. The present meta-analysis evaluated five different forms of CM (sexual,
physical, and psychological abuses, neglect, and witnessing IPV) as they
predicted sexual, psychological, and physical IPV perpetration and victimization
in men. Overall, most available studies examined men as perpetrators of IPV,
whereas studies of victimization in men were relatively scarce. Results reveal an
overall significant association ( r = .19) between CM and IPV. The magnitude of
this effect did not vary as a function of type (perpetration vs. victimization)
or form (sexual, psychological, or physical) of IPV. Although all forms of CM
were related to IPV, with effect sizes ranging from .05 (neglect and IPV
victimization) to .26 (psychological abuse and IPV victimization), these
associations varied in magnitude according to the type of CM. Findings suggest
the importance of expanding research on CM and IPV to include a range of
different kinds of abuse and neglect and to raise concerns about the experience
of men as both victims and perpetrators of IPV.
PMID- 29333984
TI - A Methodological Review and Critique of the "Intergenerational Transmission of
Violence" Literature.
AB - Exposure to interpersonal or interparental violence (EIPV) and child abuse and
maltreatment (CAM) are associated with an increased risk of maladaptive outcomes,
including later involvement in adulthood intimate partner violence (IPV; often
referred to as the theory of intergenerational transmission of violence). Recent
meta-analyses, however, have documented a weak effect size when examining this
association. By focusing on young adulthood, a development stage in which
identity development and romantic relationship formation are salient tasks, we
can provide insight into the association between EIPV, CAM, and IPV. Guided by
the methodological critiques from the IPV and EIPV literatures, the present study
reviewed the methodology used in 16 studies (published between 2002 and 2016)
that tested the theory of intergenerational transmission of violence. The review
study focused on how EIPV, CAM, and young adult dating violence were measured and
analyzed, with the initial goal of better understanding how methodological
decision informed the study's findings. Ultimately, we determined that there was
simply too much methodological variability and yet too little methodological
complexity to truly inform a review and discussion of the results; therefore, our
review solely focused on the study's methodological decisions. Based on our
review, we suggest that both of these challenges, too much variability and too
little complexity, hinder our ability to examine the theory of intergenerational
transmission of violence. Future research must strike a balance between
methodological consistency and complexity to better understand the intricate
nuances of IPV experiences and inform practice.
PMID- 29333985
TI - A Systematic Review of Interventions for Women Parenting in the Context of
Intimate Partner Violence.
AB - Intimate partner violence (IPV) victimization is widespread among women with
children and has negative consequences for both women's and children's well
being. Despite mixed evidence regarding the effect of IPV on women's parenting
ability and behaviors, there is an increasing focus on mothering in the context
of IPV, particularly among the child welfare and child protection systems. To
help respond to this increasing focus, several interventions have been developed
that specifically target parenting among IPV-affected women. Given the growing
numbers of these interventions, a comprehensive review is needed to help
elucidate the approaches that are most effective in meeting the needs of IPV
affected women and children. Therefore, we conducted an in-depth systematic
review of the literature to examine the approaches and effects of interventions
designed to address aspects of parenting among IPV-affected women. We identified
26 articles concerned with 19 distinct interventions for review. We found
substantial heterogeneity in intervention delivery, format, length, and focus. We
noted several limitations of the existing studies in terms of study sample,
measures, design, and implementation. Given the heterogeneity of the existing
interventions and the limitations of the current research base, it is not yet
clear which interventions or intervention components are most effective in
addressing the unique needs of women parenting in the context of IPV. Further
research is needed to address these limitations, and professionals working with
IPV-affected families should be aware that current services may not meet women's
and children's needs.
PMID- 29333986
TI - The Prevalence and Correlates of Partner Violence Used and Experienced by Adults
With Intellectual Disabilities: A Systematic Review and Call to Action.
AB - It has been suggested that individuals with intellectual disabilities (IDs) are
at increased risk of violence perpetration and victimization. A systematic review
was undertaken to identify and critically evaluate the existing empirical
research concerning the use and experience of partner violence by adults with
IDs. In total, six poor-quality articles were identified: five of which adopted
qualitative methods and one of which adopted a mixed-methods approach, comprising
a total of 93 participants (48 women, 45 men: 1 perpetrator, 92 victims). The
qualitative data were extracted from the studies and synthesized. A partner
violence victimization rate of 60% was identified in one nonrepresentative
sample. Two superordinate themes emerged from the qualitative data: nature of
partner violence experience and help seeking. Children were the cross-cutting
theme within the two superordinate themes. Participants reported experiencing a
range of physical, emotional, and sexual violence leading to serious injury and
psychological consequences. Participants reported experiences of positive and
negative help-seeking reactions from professionals and specific requirements of
services for victims with IDs. Children were identified as involved in the
experience of abuse, the impact of abuse, and decisions to seek help. The
findings indicate that training of clinical staff to detect partner violence is
needed. In addition, adults with IDs need education concerning healthy
relationships. Research is needed to better understand the difference between
"challenging behavior" that is behavior displayed by an individual which
challenges services, family members, and carers. Such behavior is more common in
individuals with a severe ID for whom it would not be appropriate to be dealt
with through the criminal justice system, and partner violence, in order to
develop appropriate interventions for victims and perpetrators with ID.
PMID- 29333987
TI - Comparing Long-Term Placement Outcomes of Residential and Family Foster Care: A
Meta-Analysis.
AB - This study presents findings from three separate meta-analyses investigating
differences between children placed in residential care and in family foster care
with regard to three outcomes: internalizing behaviors, externalizing behaviors,
and perception of care. Based on publications from the last 20 years, a total of
23 studies were included. The total sample consisted of 13,630 children in care,
with 7,469 from foster care and 6,161 from residential care. The results from
this study indicated that children in foster care had consistently better
experiences and less problems across the three outcomes as compared to children
in residential care. Analyses did not reveal evidence of publication bias, and
sensitivity analyses also suggested that results were not influenced by
individual studies. Additionally, moderation analyses revealed that the
differences between foster and residential care could vary depending on certain
factors such as the publication year, the gross domestic product of the country,
and the length of care. The implications of differences in outcomes between the
two placements are discussed.
PMID- 29333988
TI - Male IPV Perpetrator's Perspectives on Intervention and Change: A Systematic
Synthesis of Qualitative Studies.
AB - OBJECTIVE: To add to our understanding of change processes by analyzing
perpetrators' perspectives on intervention. METHOD: Fourteen databases were
searched and 27 articles reporting relevant qualitative findings were identified.
Analytic coding was applied across the findings and discussion sections of all 27
study reports to form an interpretive account of the data set. Studies were also
grouped according to their perceived theoretical standpoints, and a summary of
themes in each grouping is presented. FINDINGS: Study participants were largely
positive about their experiences in intervention; new learning such as conflict
interruption techniques and new communication skills were commonly cited
benefits. Perpetrators attend perpetrator intervention programs with a range of
motivations, ranging from a determination to change who they are, to a
determination to avoid a custodial sentence. The most common barriers to change,
found in this analysis, were cognitive distortions, emotional dysregulation,
gendered social constructions, and self-esteem issues. CONCLUSION: Further
qualitative investigation, of rigor, with the intention-to-treat population of
intimate partner violence perpetrators involved in perpetrator programs is
needed. At this point, we would venture that qualitative research, with
perpetrators, underlines the precept that formidable barriers to change exist in
this population. The centrality of group work to perpetrator interventions should
be reconsidered in light of the complexity of the change task and in light of the
heterogeneity of this population.
PMID- 29333989
TI - Sexual Violence Victimization Among College Females: A Systematic Review of
Rates, Barriers, and Facilitators of Health Service Utilization on Campus.
AB - To date, little work specifically addresses empirical studies concerning barriers
and facilitators to health service use among college female sexual violence
victims. The following objectives were addressed: (1) analyze studies of college
aged women who have been victims of sexual violence to examine the frequency and
moderating characteristics of utilization of university-based resources
available, (2) identify inconsistencies and gaps in the literature concerning
sexual victimization and service utilization, and (3) provide next steps for
researchers and clinical care coordinators. Six electronic databases were
searched from 1990 to May 2016. Inclusion criteria for the review were (1)
university or college setting or sample, (2) empirical design, and (3) inclusion
of some discussion or measurement of health service use. Following preferred
reporting items for systematic reviews and meta-analyses (PRISMA) procedures, 22
articles were identified for the review. Although prevalence rates of sexual
victimization were high (4.7-58%), rates of service utilization were lower (0
42%). There were significant discrepancies between hypothetical use of services
and actual rates of service use. Identified barriers included feelings of shame,
guilt and embarrassment, not wanting friends and family to find out, and thinking
the victimization was not serious enough to report. Identified facilitators
included acknowledging the sexual violence victimization as a crime, receiving
encouragement from friends and family to utilize health services, and receiving a
positive response during the initial informal disclosure. Finally, measurement of
victimization was inconsistent across studies. Recommendations are offered for
college campus prevention programming and future research.
PMID- 29333990
TI - Child Sexual Abuse: Toward a Conceptual Model and Definition.
AB - The problem of defining "child sexual abuse" (CSA), and the need to define this
concept, has been recognized by major policy bodies and leading researchers since
the 1970s. Recent demands for a more theoretically robust, explicit definition of
CSA show this challenge remains urgent. In this article, we identify problems
caused by variance in definitions of CSA for five domains: research and knowledge
formation, legal frameworks and principles, prevention efforts, policy responses,
and the establishment of social norms. We review and analyze definitions used in
leading international epidemiological studies, national and international policy
documents, social science literature, and legal systems in the United States,
Canada, and Australia to demonstrate the continuing use of different concepts of
CSA and identify key areas of conceptual disagreement. Informed by our literature
review, we use a methodology of conceptual analysis to develop a conceptual model
of CSA. The purpose of this model is to propose a more robust, theoretically
sound concept of CSA, which clarifies its defining characteristics and
distinguishes it from other concepts. Finally, we provide operational examples of
the conceptual model to indicate how it would translate to a classificatory
framework of typologies of acts and experiences. A sound conceptual model and
classificatory system offers the prospect of more appropriate and effective
methods of research, response, regulation, and prevention. While total consensus
is unattainable, this analysis may assist in developing understanding and
advancing more coherent approaches to the conceptual foundation of CSA and its
operationalization.
PMID- 29333991
TI - Evaluation of a portable gas chromatograph with photoionization detector under
variations of VOC concentration, temperature, and relative humidity.
AB - The objective of this present study was to evaluate the performance of a portable
gas chromatograph-photoionization detector (GC-PID), under various test
conditions to determine if it could be used in occupational settings. A mixture
of 7 volatile organic compounds (VOCs)-acetone, ethylbenzene, methyl isobutyl
ketone, toluene, m-xylene, p-xylene, and o-xylene-was selected because its
components are commonly present in paint manufacturing industries. A full
factorial combination of 4 concentration levels (exposure scenarios) of VOC
mixtures, 3 different temperatures (25 degrees C, 30 degrees C, and 35 degrees
C), and 3 relative humidities (RHs; 25%, 50%, and 75%) was conducted in a full
size controlled environmental chamber. Three repetitions were conducted for each
test condition allowing for estimation of accuracy. Time-weighted average
exposure data were collected using solid sorbent tubes (Anasorb 747, SKC Inc.) as
the reference sampling medium. Calibration curves of Frog-4000 using the dry
gases showed R2 > 0.99 for all analytes except for toluene (R2 = 0.97). Frog-4000
estimates within a test condition showed good consistency for the performance of
repeated measurement. However, there was ~41-64% reduction in the analysis of
polar acetone with 75% RH relative to collection at 25% RH. Although Frog-4000
results correlated well with solid sorbent tubes (r = 0.808-0.993, except for
toluene) most of the combinations regardless of analyte did not meet the <25%
accuracy criterion recommended by NIOSH. The effect of chromatographic co-elution
can be seen with m, p-xylene when the results are compared to the sorbent tube
sampling technique with GC-flame ionization detector. The results indicated an
effect of humidity on the quantification of the polar compounds that might be
attributed to the pre-concentrator placed in the selected GC-PID. Further
investigation may resolve the humidity effect on sorbent trap with micro GC pre
concentrator when water vapor is present. Although this instrument does not
fulfill the accuracy criterion specified in the NIOSH technical report No. 2012
162, it can be used as a screening tool for range finding monitoring with dry
gases calibration in the occupational setting rather than compliance monitoring.
PMID- 29333992
TI - Insecure Adult Attachment and Child Maltreatment: A Meta-Analysis.
AB - Extant evidence has shown that insecure adult attachment is related to
dysfunctional parenting styles that heighten parents' risk of child maltreatment.
However, there is a lack of studies appraising the evidence for the association
between insecure adult attachment and child maltreatment. This meta-analytic
study examined the relationship between parents' adult attachment and child
maltreatment perpetration/child abuse potential. Studies examining the
relationship between parents' adult attachment and child maltreatment/child abuse
potential published before February 2017 were identified through a systematic
search of online databases. In total, 16 studies ( N = 1,830) were selected. Meta
analysis based on random-effects models shows a significant positive association
between insecure attachment and child maltreatment (pooled effect size: odds
ratio [ OR] = 2.93, p = .000). Subgroup analyses show insecure attachment was
more strongly associated with failure to thrive ( OR = 8.04, p = .000) and
filicide ( OR = 5.00, p < .05). Medium effect sizes were found for subgroup
analyses on insecure romantic attachment ( OR = 3.76, p = .000), general
attachment ( OR = 3.38, p = .000), attachment to own child ( OR = 3.13, p =
.001), and to own parents ( OR = 2.63, p = .000) in relation to child
maltreatment.
PMID- 29333993
TI - History of environmental and occupational health.
PMID- 29333994
TI - The Association Between Serious Mental Health Problems and Violence: Some Common
Assumptions and Misconceptions.
AB - The media, the general public, and politicians often emphasize that mental
illness is a precursor and a cause of violence, particularly emphasizing an
assumed relationship between mental illness, including psychopathy and psychosis,
and the use of guns to commit violence. We report which individuals with serious
mental health problems have an increased risk to commit violence (including gun
violence). Second, we answer the question to what extent serious mental health
problems explain most violence and especially gun-related violence. And what is
the opinion of experts on these questions? Third, we review which effective
screening instrument can help to identify individuals with mental health problems
who are at risk to carry a gun and commit violence. For policy makers and
legislators, this article points out that most psychiatric disorders are not
related to violence, with some exceptions such as schizophrenia and bipolar
disorder, and often only in conjunction with substance use. We show that the
attributable risk of mental illness to explain violence in general is low. We
also emphasize that conduct disorder in late childhood or adolescence is a better
predictor of violence than is mental illness at a later age. Empirically based
screening methods to identify individuals with mental health problems who are
prone to violence appear to have limited utility. Implications are discussed for
clinicians and practitioners working in the justice system, researchers, and
policy makers.
PMID- 29333995
TI - Violence Against International Students: A Critical Gap in the Literature.
AB - Despite the growing trend on college campuses to increase their international
student body, this population is largely left out of research due to the
complexity they bring to the research process compared to their domestic
counterparts. This is particularly true for the existing research on campus
sexual violence; thus, there is no research-based indication that international
students, let alone international graduate students, would face victimization
risks on campus in the same way the extant literature identifies for domestic
undergraduates. The existing research on international students indicates that
their experiences are different than their domestic counterparts, and the sparse
literature on graduate students indicates their experiences are different from
their undergraduate counterparts. A specific focus on the intersection of these
two identities, international graduate students, is almost completely absent from
the literature. This research review highlights key research that provides
foundational knowledge for the experience of international students and
international graduate students with regard to their vulnerability to sexual
violence. The author organizes the extant literature into three major areas that
inform the overarching research topic: (1) international student experiences, (2)
victimization, and (3) campus culture. Basic findings indicate that there are
limitations in extrapolating previous research findings on campus sexual violence
to this population, calling for a need to focus specifically and intentionally on
this population of students. The objective of this article is to review the
current state of knowledge about the risk and vulnerability of international
students to sexual violence and victimization and to address the directions for
future research.
PMID- 29333996
TI - Energy Expenditure and Intensity of Active Video Games in Children and
Adolescents.
AB - PURPOSE: This study aimed to compare the energy expenditure and intensity of
active video games to that of treadmill walking in children and adolescents.
METHOD: Seventy-two boys and girls (aged 8-13 years) were recruited from local
public schools. Energy expenditure and heart rate were measured during rest,
during 3-km/hr, 4-km/hr, and 5-km/hr walks, and during active games (Adventure,
Boxing I, Boxing II, and Dance). During walking and active games, we also
assessed physical activity using an accelerometer. RESULTS: The energy
expenditure of the active games Adventure, Boxing I, Boxing II, and Dance was
similar to that of treadmill walking at 5 km/hr in boys and girls. Heart rate was
significantly higher for the game Adventure compared with walking at 3 km/hr, 4
km/hr, and 5 km/hr and the game Dance in both genders. The heart rate of girls
during the games Adventure and Dance was significantly higher compared with boys.
There was a statistically significant difference (p < .05, with an effect size
ranging from 0.40 to 3.54) in the counts.min-1, measured through accelerometry,
between activities. CONCLUSION: XBOX 360 Kinect games provide energy expenditure
and physical activity of moderate intensity for both genders. The use of active
video games can be an interesting alternative to increase physical activity
levels.
PMID- 29333997
TI - Understanding the Relationship Between Male Gender Socialization and Gender-Based
Violence Among Refugees in Sub-Saharan Africa.
AB - Gender-based violence (GBV) in humanitarian emergencies is progressively
recognized as a global public health problem. Detrimental gender norms influence
male perpetrated GBV against women, and social and structural contexts of forced
migration and camp resettlement contribute to problematic gender norm
development. The review sought to elucidate the dynamics that link gender
socialization among male youth in sub-Saharan Africa with violent sexual
behaviors. Two concepts were explored: (1) male gender socialization in sub
Saharan Africa related to GBV perpetration patterns and (2) the effect of forced
migration on male socialization and GBV. We reviewed articles using a standard
systematic review methodology, searching academic databases for peer-reviewed
articles, and contacting experts for gray literature. Our initial search
identified 210 articles. We manually reviewed these, and 19 met the review
inclusion criteria. We identified 20 variables from the first concept and 18
variables from the second. GBV perpetration by male youth is positively
associated with social pressures as well as cultural and religious beliefs. Amid
forced migration, personal, societal, and cultural preexisting gender
inequalities are often amplified to encourage GBV perpetration. The literature
revealed aspects of culture, language, role modeling, religion, and the context
of violence as important factors that shape young men's perspectives regarding
the opposite sex and gender relations as well as sexual desires and dominance.
Overall, though, literature focusing on male socialization and GBV prevention is
limited. We made recommendations for future studies among refugee male youth in
order to better understand these relationships.
PMID- 29333998
TI - When Older People Are Violent or Abusive Toward Their Family Caregiver: A Review
of Mixed-Methods Research.
AB - What happens when family caregivers experience violence and abuse from the older
person for whom they care? Although this issue has received little global
attention, it is relevant to researchers, practitioners, and policy makers
working across the intersecting fields of older age care and medicine, adult
protection and safeguarding, and domestic and intimate partner violence. To date,
these fields have generated diverse explanations of violence and abuse in older
age illness and how best to respond to it. This article reports the findings of a
systematic literature review of 18 quantitative, qualitative, and mixed-methods
studies that investigated violent and abusive behavior by older people toward
their family caregivers. The review identified three central themes in the
literature: (1) There are inconsistent definitions and measurements used in
research about harmful, violent, and abusive behavior toward family caregivers.
(2) Violent and abusive behavior toward caregivers is a sensitive and hidden
topic that poses practical and methodological challenges for researchers. (3)
There is some evidence to suggest that people who were violent and abusive in
their earlier life-or who had a poor relationship with their family member in the
past-are more likely to continue to experience violence and abusive behavior in
later life. There were two central ways in which violence and abuse were
conceptualized and investigated: as a "symptom of illness" or as an "act of
abuse" and we present a visual map of the relationship between these two
conceptualizations drawn from our analysis of the literature. We conclude by
discussing the implications of the findings and recommend future directions for
practice, research, and policy to support affected families.
PMID- 29333999
TI - Consequences of Elder Abuse and Neglect: A Systematic Review of Observational
Studies.
AB - This article presents the results of a systematic review of the consequences of
elder abuse and neglect (EAN). A systematic search was conducted in seven
electronic databases and three sources of gray literature up to January 8, 2016,
supplemented by scanning of citation lists in relevant articles and contact with
field experts. All observational studies investigating elder abuse as a risk
factor for adverse health outcomes, mortality, and health-care utilization were
included. Of 517 articles initially captured, 19 articles met our inclusion
criteria and were analyzed. Two reviewers independently performed abstract
screening, full-texts appraisal, and quality assessment using the Newcastle
Ottawa Scale. Across 19 studies, methodological heterogeneity was a prominent
feature; seven definitions of EAN and nine measurement tools for abuse were
employed. Summary of results reveals a wide range of EAN outcomes, from premature
mortality to increased health-care consumption and various forms of physical and
psychological symptoms. Higher risks of mortality emerged as the most credible
outcome, while the majority of morbidity outcomes originated from cross-sectional
studies. Our findings suggest that there is an underrepresentation of older
adults from non-Western populations and developing countries, and there is a need
for more population-based prospective studies in middle- and low-income regions.
Evidence gathered from this review is crucial in upgrading current practices,
formulating policies, and shaping the future direction of research.
PMID- 29334000
TI - Predictors of Interpersonal Violence in the Household in Humanitarian Settings: A
Systematic Review.
AB - Interpersonal violence against women and children has increasingly been
recognized as a public health priority in humanitarian emergencies. However,
because the household is generally considered a private sphere, violence between
family members remains neglected. A systematic literature review was conducted to
identify predictors of household violence in humanitarian emergencies. PubMed,
Web of Science, and Scopus were searched from January 1, 1998, to February 16,
2016. A predictor was defined as any individual, household, or community-level
exposure that increases or decreases the risk associated with physical, sexual,
or emotional interpersonal violence between two or more people living together.
All studies reporting on quantitative research were eligible for inclusion.
Results were analyzed using qualitative synthesis. Preferred Reporting Items for
Systematic Reviews and Meta-Analyses guidelines were followed as applicable. The
search strategy resulted in 2,587 original records, of which 33 studies met
inclusion criteria. Thirty-two of the 33 studies used a cross-sectional design.
This was the first known systematic review of predictors of household violence in
humanitarian settings. The household framework drew attention to several factors
that are associated with violence against both women and children, including
conflict exposure, alcohol and drug use, income/economic status, mental
health/coping strategies, and limited social support. There is a need for
longitudinal research and experimental designs that can better establish
temporality between exposures and household violence outcomes, control for
confounding, and inform practice. In the interim, programmers and policy makers
should try to leverage the predictors identified by this review for integrated
violence prevention and response strategies, with the important caveat that
ongoing evaluation of such strategies is needed.
PMID- 29334001
TI - Integrated Multicomponent Interventions for Safety and Health Risks Among Black
Female Survivors of Violence: A Systematic Review.
AB - The epidemic of violence disproportionately affects women, including Black women.
Black women survivors of violence have been found to face multiple safety and
health issues such as depression, post-traumatic stress disorder, HIV, and poor
reproductive health. Many health issues co-occur, and this co-occurrence can be
associated with additional safety and health-related challenges for survivors.
Consequently, there is a need for multicomponent interventions that are designed
to concurrently address multiple health issues commonly faced by Black survivors
of violence. This systematic review of literature determines the efficacy of
various strategies used in the existing evidence-based multicomponent
interventions on violence reduction, promotion of reproductive health, reduction
in risk for HIV, reduction in levels of stress, and improvement in mental health.
Sixteen intervention studies were identified. Examples of components found to be
efficacious in the studies were safety planning for violence, skill building in
self-care for mental health, education and self-regulatory skills for HIV,
mindfulness-based stress reduction for reducing stress, and individual counseling
for reproductive health. Although some strategies were found to be efficacious in
improving outcomes for survivors, the limitations in designs and methods, and
exclusive focus on intimate partner violence calls for more rigorous research for
this population, particularly for Black survivors of all forms of violence. There
is also need for culturally responsive multicomponent interventions that account
for diversity among Black survivors.
PMID- 29334002
TI - Concordance Between Parents in Perpetration of Child Mistreatment: How Often Is
It by Father-Only, Mother-Only, or by Both and What Difference Does It Make?
AB - Research on child mistreatment tends to focus on the mother or the father as the
abusing parent, even though there is wide agreement that both theory and practice
should deal with child maltreatment as a family system problem. Most children
have the benefit or the risk of more than one caretaker for substantial periods
of their lives, most often two parents or stepparents. This article is intended
to illustrate the value of research which uses concordance analysis (CA) to
identify children who experienced three dyadic concordance types (DCTs) of
mistreatment: father-only, mother-only, or both parents, including single-parent
combinations of caretakers. A concordance approach that identifies possible
abusers in addition to the presenting parent using the three DCTs is a practical
first step toward a family system perspective to enhance child abuse theory,
research, and practice.
PMID- 29334003
TI - Removing Firearms From Those Prohibited From Possession by Domestic Violence
Restraining Orders: A Survey and Analysis of State Laws.
AB - Under federal and many state laws, persons under domestic violence restraining
orders (DVROs) are prohibited from possession of firearms. Using multiple sources
and a Lexis Nexis search, we developed a list of state laws pertaining to the
relinquishment or removal of firearms from persons prohibited from possession by
DVROs. After downloading the text of each law, we conducted a legal analysis to
enumerate provisions of the laws specifying implementation. We found 49 laws in
29 states and Washington, DC. The laws were conceptualized as instructions to the
court, the respondent, and law enforcement. We detail the content of each state's
law, including such elements as whether it applies to ex parte DVROs; whether
certain criteria must be met, such as previous use of a firearm in domestic
violence or lack of an employment exemption, before the law can be applied; and
whether the application of the law is mandatory. We also detail instructions to
the respondent regarding to whom firearms may be relinquished, whether the
respondent must seek permission to transfer the firearm to a third party, and the
time by which dispossession must occur. Finally, whether law enforcement bears
the responsibility for removing the firearm or whether the law gives the court
the authority to order a search and seizure for the firearms is discussed. The
purpose of the research is to provide an overview of these state laws that can be
used by key stakeholders in legislative, judicial, advocacy, or research roles.
Implications are discussed.
PMID- 29334004
TI - Examining residence status as a risk factor for health risk behaviors among
college students.
AB - OBJECTIVE: The current study is aimed to evaluate college student residence as a
unique risk factor for a range of negative health behaviors. PARTICIPANTS: We
examined data from 63,555 students (66% females) from 157 campuses who completed
the National College Health Assessment Survey in Spring 2011. METHODS:
Participants answered questions about the frequency of recent use of alcohol,
tobacco, marijuana, and illicit drugs, as well as sexual risk behavior in the
last 30 days. Sexual risk behaviors were operationalized as having unprotected
vaginal sex (yes/no) and the number of sexual partners. RESULTS: Logistic
regression analyses revealed that living off-campus is a unique predictor of
alcohol, tobacco, marijuana, and illicit drug use, as well as engaging in
unprotected sex and a greater number of sexual partners (all ps <. 01).
CONCLUSIONS: Students living off-campus exhibit more substance use and sexual
risk behaviors than students living on-campus, independent of gender, age, or
race.
PMID- 29334006
TI - The Intersection of Firearms and Intimate Partner Homicide in 15 Nations.
AB - Intimate partners commit approximately one in three homicides against women
worldwide. Little is known about situational factors that contribute to intimate
partner homicides (IPH) and how they may differ across nations. This article
provides a cross-national exploration of one situational factor, the use of
firearms in the commission of homicides, and considers whether nations have laws
designed specifically to keep firearms out of the hands of batterers. We
conducted a systematic search of peer-reviewed research and governmental and
nongovernmental reports for data on weapon use in IPH. Data were located for 15
nations and subnational areas, which varied from firearms being involved in no
IPHs in Fiji to 59% in Antalya, Turkey. Seven nations have legislation that
addresses gun ownership as it relates to those who have been charged with,
convicted of, or show a propensity toward the commission of intimate partner
violence. These laws vary in whether domestic violence is a factor considered in
whether to allow firearm ownership or whether it served to disqualify ownership.
Due to the small number of nations for which data on weapon use in IPH were
located, we did not conduct any hypothesis testing. There is a need for detailed
homicide surveillance systems among nations so that researchers can explore the
epidemiology of these homicides and ultimately identify opportunities for
intervention.
PMID- 29334005
TI - Physiological Correlations With Short, Medium, and Long Cycling Time-Trial
Performance.
AB - PURPOSE: Several studies have demonstrated that physiological variables predict
cycling endurance performance. However, it is still unclear whether the
predictors will change over different performance durations. The aim of this
study was to assess the correlations between physiological variables and cycling
time trials with different durations. METHODS: Twenty trained male cyclists
(maximal oxygen uptake [VO2max] = 60.5 +/- 5.6 mL/kg/min) performed 4 separate
experimental trials during a 2-week period. Cyclists initially completed an
incremental exercise test until volitional exhaustion followed by 3 maximal
cycling time trials on separate days. Each time trial consisted of 3 different
durations: 5 min, 20 min, and 60 min performed in a randomized order. RESULTS:
The main results showed that the physiological measures strongly correlated with
long cycling performances rather than short and medium time trials. The time
trial mean power output was moderately high to highly correlated with peak power
output and VO2max (r = .61-.87, r = .72-.89, respectively), and was moderately to
highly correlated with the lactate threshold Dmax method and second ventilatory
threshold (r = .52-.75, r = .55-.82, respectively). CONCLUSIONS: Therefore,
trained cyclists should develop maximal aerobic power irrespective of the
duration of time trial, as well as enhancements in metabolic thresholds for long
duration time trials.
PMID- 29334007
TI - Understanding (and Acting On) 20 Years of Research on Violence and LGBTQ +
Communities.
AB - Questions related to violence, vulnerability, and sexual and gender minorities
continuing to occupy a focal place in U.S. public discourse. We reviewed findings
from 20 years of research on that topic to make recommendations for policy,
practice, and future research. This article synthesizes findings from 102 peer
reviewed articles as well as a small number of unpublished studies and grey
literature. We found no data to support the idea (widespread in popular
discourse) that those in the sexual or gender majority require protection from
sexual or gender minority individuals. Instead, this wide body of research
indicates that sexual and gender minorities are themselves at elevated risk for
physical and sexual assault, harassment, bullying, and hate crime victimization
throughout childhood, adolescence, and adulthood. Contradicting the image of hate
crimes as perpetrated by strangers or acquaintances, we find that bias-related
verbal abuse, physical, and sexual assault by close family members contribute
heavily to observed victimization rates. Further, despite the perception that
society is becoming more welcoming, victimization disparities appear to be stable
or widening since the 1990s. More studies with probabilistic sampling approaches,
standardized measures, and larger samples of gender minorities are needed.
However, widespread victimization of sexual and gender minorities is clearly an
urgent issue, demanding attention from clinicians, program developers, and policy
makers.
PMID- 29334008
TI - Who Are the Victims and Who Are the Perpetrators in Dating Violence?: Sharing the
Role of Victim and Perpetrator.
AB - BACKGROUND: Dating violence (DV) is a serious problem with devastating
consequences. Often, research on DV has focused on two distinct groups: victims
and perpetrators. However, there is growing evidence for a victim-perpetrator
overlap model, which posits that those involved in DV are more likely to take on
both roles, rather than either role on its own. PURPOSE: We investigated the
patterns of involvement in DV among those who identified themselves as victims or
perpetrators in previous studies. METHOD: This was a systematic review and meta
analysis. A total of 371 variables related to participants' previous and
concurrent experiences of DV victimization or perpetration (202 variables related
to victimization and 169 related to perpetration) were identified in 25 studies,
which were found by systematically searching three databases: PubMed, Web of
Science, and SCOPUS. RESULTS: The majority of previous studies categorized study
participants as either DV victims or perpetrators; however, those who identified
themselves as either DV victims or DV perpetrators were more likely to assume the
opposite role as well. Specifically, current DV perpetrators had a strong
association with previous or concurrent victimization experiences, and current DV
victims were similarly likely to have assumed the roles of both victim and
perpetrator in their histories. CONCLUSION: Further efforts should be put into
avoiding categorization of those involved in violence; rather, they should be
regarded as a single group. Additionally, evidence-based interventions should be
developed for this population to help break the cycle of violence.
PMID- 29334009
TI - Perspectives in obesity and pregnancy.
AB - Obesity is currently recognized as a health epidemic worldwide. Its prevalence
has doubled in the last three decades. Obesity is a complex clinical picture
associated with physical, physiologic, hormonal, genetic, cultural, socioeconomic
and environmental factors. The rate of obesity is also increasing in the pregnant
women population. Maternal obesity is associated with less than optimal
obstetrical, fetal and neonatal outcomes. It is also associated with significant
adverse long-term effects on both obese parturients and the infants born from
obese women. A number of guidelines have been published to educate health care
workers and the general population in an attempt to develop effective
interventions on a large scale to prevent obesity. These guidelines are multiple,
confusing and inconsistent. There are no standard recommendations regarding
gestational weight gaining goals, nutrients and additional elements necessary for
certain obese women who have been treated with bariatric surgical procedures,
screening for metabolic diseases such as diabetes, additional preventive health
care services indicated for obese women in the pregnancy planning stages, during
prenatal care, in the immediate post-partum period and as a long-term approach
for health preservation. In 2013, the American Medical Association supported by
several US national medical specialty organizations published Resolution 420 (A
13) recognizing obesity as a disease state with multiple pathophysiological
aspects requiring a range of interventions to improve its prevention and
treatment. The goal of this decision was to encourage a broader spectrum of
health care benefits insurance coverage for the prevention and treatment of
obesity. There are a number of myths and misconceptions associated with obesity.
These perspectives present our views and clinical experience with a partial
review of recent bibliography addressing the associations between obese
reproductive age women and their risks during pregnancy.
PMID- 29334012
TI - Better Together? A Review of Evidence for Multi-Disciplinary Teams Responding to
Physical and Sexual Child Abuse.
AB - Multi-Disciplinary teams (MDTs) have often been presented as the key to dealing
with a number of intractable problems associated with responding to allegations
of physical and sexual child abuse. While these approaches have proliferated
internationally, researchers have complained of the lack of a specific evidence
base identifying the processes and structures supporting multi-disciplinary work
and how these contribute to high-level outcomes. This systematic search of the
literature aims to synthesize the existing state of knowledge on the
effectiveness of MDTs. This review found that overall there is reasonable
evidence to support the idea that MDTs are effective in improving criminal
justice and mental health responses compared to standard agency practices. The
next step toward developing a viable evidence base to inform these types of
approaches seems to be to more clearly identify the mechanisms associated with
effective MDTs in order to better inform how they are planned and implemented.
PMID- 29334010
TI - Esmya(r) and the PEARL studies: A review.
AB - Ulipristal acetate was investigated in four phase 3 trials. In PEARL I,
ulipristal produced significant normalisation of blood loss within 1 week and
decreased fibroid volume. In PEARL II, ulipristal produced faster and more
consistent control of bleeding than leuprorelin acetate and had a more favourable
side-effect profile. Ulipristal-induced decreases in fibroid volume persisted for
6 months, whereas fibroids regrew after leuprorelin was stopped. PEARL III showed
that ulipristal was effective during long-term treatment, with norethisterone
further reducing the magnitude of bleeding in the off-treatment period. PEARL IV
investigated ulipristal over four cycles, finding little difference between 5 and
10 mg ulipristal, further changes in menstruation and fibroid volume with repeat
courses, and no increase in side effects.
PMID- 29334011
TI - A qualitative study of cervical cancer and cervical cancer screening awareness
among nurses in Ghana.
AB - Despite the availability of cervical cancer screening tools, including those that
are appropriate for low resource settings, the rates of preventive cervical
cancer screening remain extremely low among women in LMICS. Nurse-led education
interventions have been proven to be effective at increasing participation in
healthcare recommendations. However, there is a need to determine nurses'
knowledge of cervical cancer and cervical cancer prevention in order to develop
effective health education interventions. Our goal was to assess Ghanaian nurses'
knowledge of cervical cancer and cervical cancer prevention. Interviews and small
focus groups were conducted with 42 nurses at two hospitals in Ghana. Awareness
of cervical cancer was very high among the nurses. However, the majority of the
participants held negative perceptions about cervical cancer and lacked knowledge
about cervical cancer risk factors and prevention. The results can be used to
inform the development of culturally-relevant cervical cancer education
interventions targeted towards women and healthcare providers in LMICs.
PMID- 29334013
TI - Understanding Teacher Change: A National Survey of U.S. Physical Educators.
AB - : Physical education is critical to addressing childhood obesity, yet many school
based programs do not meet established quality standards and teachers are called
upon to change. Little is known about how change is initiated and its associated
internal and external factors. PURPOSE: The purpose of this study was to
investigate physical education teacher change that was self-initiated and
externally initiated and to examine dispositions toward the change process
relative to initiation. METHOD: A random national sample of physical educators
representing each SHAPE America - Society of Health and Physical Educators
regional district participated in a survey measuring past programming changes,
primary initiators of change, and teachers' dispositions toward change. In total,
2,423 teachers (46% response rate) completed electronic, paper, or telephone
questionnaires. RESULTS: Teachers most often made minor curriculum changes, and
they added/subtracted student assessments (primarily informal assessments) least
often. Self-initiated (bottom-up) change was most frequently (83.1% of the time)
reported. Externally initiated (top-down) changes were less frequent and were
most often associated with professional development. Teachers reported
principals' involvement in both top-down and bottom-up change processes was
minimal. Teachers who were more disposed to making future changes reported making
significantly (p < .01, eta2 = .046-.119) more past changes than those who were
less disposed to change. CONCLUSIONS: Physical education teachers primarily self
initiated minor programming changes without involvement from administration.
Externally initiated change was infrequent and mostly involved professional
development. Dispositions toward change were individual and enduring such that
teachers who had made more past changes were more likely to also make future
changes.
PMID- 29334014
TI - Using Applied Theater in Primary, Secondary, and Tertiary Prevention of Intimate
Partner Violence: A Systematic Review.
AB - There is an immediate need to advance knowledge around the effective prevention
of intimate partner violence (IPV), which is responsible for significant negative
health and well-being outcomes for women around the world. Creative approaches
are being explored internationally-this systematic review provides a timely
synthesis of applied theater interventions addressing primary, secondary, and
tertiary IPV prevention. Six hundred and ten articles were identified through a
comprehensive search of five cross-disciplinary databases. Eleven studies
discussed in 15 quantitative and qualitative peer-reviewed articles and one book
chapter met the inclusion criteria and were included in the review. Articles were
appraised using a standardized quality assessment tool and were analyzed within
the context of IPV prevention. Of the reviewed studies, five were classified as
primary prevention, four secondary, and two focused on tertiary prevention.
Specific strategies used by each of the studies included healthy relationship
training, rising awareness and community advocacy, service provider training,
bystander training, and working with survivors. While the paucity and quality of
current literature make it difficult to determine overall efficacy, this review
points to the potential of applied theater as a useful prevention strategy,
particularly when interactive, participatory methods are incorporated. Further,
applied theater could be an effective tool for working in culturally diverse
settings as well as with minority groups. Future applied theater program planning
needs to include comprehensive evaluation. More rigorous investigation, involving
mixed-method research approaches, is required to fully understand the potential
of applied theater as a tool in the context of IPV prevention.
PMID- 29334015
TI - Efficacy of hyperbaric oxygen therapy in bacterial biofilm eradication.
AB - OBJECTIVE: Chronic wounds typically require several concurrent therapies, such as
debridement, pressure offloading, and systemic and/or topical antibiotics. The
aim of this study was to examine the efficacy of hyperbaric oxygen therapy (HBOT)
towards reducing or eliminating bacterial biofilms in vitro and in vivo. METHOD:
Efficacy was determined using in vitro grown biofilms subjected directly to HBOT
for 30, 60 and 90 minutes, followed by cell viability determination using
propidium monoazide-polymerase chain reaction (PMA-PCR). The efficacy of HBOT in
vivo was studied by searching our chronic patient wound database and comparing
time-to-healing between patients who did and did not receive HBOT as part of
their treatment. RESULTS: In vitro data showed small but significant decreases in
cell viability at the 30- and 90-minute time points in the HBOT group. The in
vivo data showed reductions in bacterial load for patients who underwent HBOT,
and ~1 week shorter treatment durations. Additionally, in patients' chronic
wounds there was a considerable emergence of anaerobic bacteria and fungi between
intermittent HBOT treatments. CONCLUSION: The data demonstrate that HBOT does
possess a certain degree of biofilm killing capability. Moreover, as an adjuvant
to standard treatment, more favourable patient outcomes are achieved through a
quicker time-to-healing which reduces the chance of complications. Furthermore,
the data provided insights into biofilm adaptations to challenges presented by
this treatment strategy which should be kept in mind when treating chronic
wounds. Further studies will be necessary to evaluate the benefits and mechanisms
of HBOT, not only for patients with chronic wounds but other chronic infections
caused by bacterial biofilms.
PMID- 29334016
TI - Case report to demonstrate the need for selection criteria for optimal adjustable
Velcro wrap prescription.
AB - Compression, in the form of either a compression bandage or a compression
stocking, has been touted as the gold standard for treatment of swelling and
venous leg ulcers (VLUs). Adjustable Velcro wraps have been marketed as
compression alternative. Although there is a growing body of evidence to support
use of these products, there has not been a critical evaluation of the
functionality of the devices to best matching product to patient presentation and
ability to use the device effectively. Unlike compression garments, which are
classified by compression category (class I/II or flat knit/circular), there is
not an algorithm to direct health professionals to best match a specific
adjustable Velcro wrap to an individual patient presentation. This small case
series demonstrates that although each product performed as marketed in vitro,
performance in clinical setting varied greatly dependent on patient presentation
and functional skill level.
PMID- 29334017
TI - Simplifying the simple: pressure-based tissue injuries for dummies.
PMID- 29334018
TI - Pyoderma gangrenosum demographics, treatments, and outcomes: an analysis of 2,273
cases.
AB - OBJECTIVE: Pyoderma gangrenosum is a rare, neutrophil-mediated, auto-inflammatory
dermatosis. This condition has clinical features analogous to infectious
processes and must be quickly diagnosed to be properly treated. The purpose of
this study was to characterise relevant clinical features associated with
pyoderma gangrenosum based on a large inpatient cohort. METHOD: The National
Inpatient Sample (US) was used to identify patients with the diagnosis of
pyoderma gangrenosum using ICD-9 diagnosis code 686.01, during the years 2008
2010. Data was collected on demographics, associated diagnoses, treatments and
outcomes. Data analysis was performed using SAS 9.3 software. RESULTS: A total of
2,273 adult patients were identified with pyoderma gangrenosum. Mean age was 56
years; 66.4% were female; 71.1% were Caucasian. Pyoderma gangrenosum was the
primary diagnosis in 22.6% of patients, followed by cellulitis (9.4%),
inflammatory bowel disease (IBD) (6.9%), wound/ulcer (5.4%), sepsis (4.7%), and
postoperative infection/complication (2.7%). The most common procedures performed
were wound debridement (5.3%), skin biopsy (5.1%), esophagogastroduodenoscopy
(2%), large bowel biopsy (1.9%), and incision and drainage (1.1%). A total of 74
patients (3.2%) died during hospitalisation. CONCLUSION: Pyoderma gangrenosum is
a serious skin condition, frequently associated with systemic disease, and often
confused with other skin pathergies. Pyoderma gangrenosum should be considered
when evaluating patients with ulcers, wounds, and post-operative complications. A
high index of suspicion is necessary for early and accurate diagnosis and prompt
treatment.
PMID- 29334019
TI - Chemical stabilization of polymers: Implications for dermal exposure to
additives.
AB - Technical benefits of additives in polymers stand in marked contrast to their
associated health risks. Here, a multi-analyte method based on gas chromatography
coupled to tandem mass spectrometry (GC-MS/MS) was developed to quantify polymer
additives in complex matrices such as low-density polyethylene (LDPE) and
isolated human skin layers after dermal exposure ex vivo. That way both technical
aspects and dermal exposure were investigated. The effects of polymer
additivation on the material were studied using the example of LDPE. To this end,
a tailor-made polymer was applied in aging studies that had been furnished with
two different mixtures of phenol- and diarylamine-based antioxidants,
plasticizers and processing aids. Upon accelerated thermo-oxidative aging of the
material, the formation of LDPE degradation products was monitored with
attenuated total reflectance-Fourier transformed infrared (ATR-FTIR)
spectroscopy. Compared to pure LDPE, a protective effect of added antioxidants
could be observed on the integrity of the polymer. Further, thermo-oxidative
degradation of the additives and its kinetics were investigated using LDPE or
squalane as matrix. The half-lives of additives in both matrices revealed
significant differences between the tested additives as well as between LDPE and
squalane. For instance, 2-tert-butyl-6-[(3-tert-butyl-2-hydroxy-5
methylphenyl)methyl]-4-methylphenol (Antioxidant 2246) showed a half-life 12
times lower when incorporated in LDPE as compared to squalane. As a model for
dermal exposure of consumers, human skin was brought into contact with the tailor
made LDPE containing additives ex vivo in static Franz diffusion cells. The skin
was then analyzed for additives and decomposition products. This study proved 10
polymer additives of diverse pysicochemical properties and functionalities to
migrate out of the polymer and eventually overcome the intact human skin barrier
during contact. Moreover, their individual distribution within distinct skin
layers was demonstrated. This is exemplified by the penetration of the
procarcinogenic antioxidant N-phenylnaphthalen-2-amine (Neozon D) into the viable
epidermis and the permeation through the skin of the neurotoxic plasticizer N
butylbenzenesulfonamide (NBBS). In addition, the analyses of additive degradation
products in the isolated skin layers revealed the presence of 2-tert-butyl-4
methylphenol in all layers after contact to a polymer with substances of origin
like Antioxidant 2246. Thus, attention needs to be paid to absorption of polymer
additives together with their degradation products when it comes to dermal
exposure assessment.
PMID- 29334020
TI - Gender-atypical personality or sexual behavior: What is disgusting about male
homosexuality?
AB - Research consistently finds that homosexuality elicits strong feelings of
disgust, but the reasons remain unclear. In the current research, we investigate
responses to gay men who violate social norms governing the expression of gender
and sexuality. Two hundred forty-three college undergraduates read a vignette
about a gay male college student whose personality traits (masculine, feminine,
or neutral) and sexual behavior (active vs. passive) varied and reported their
affective responses to and cognitive appraisals of the target. The gay target who
displayed a feminine personality elicited more disgust and was perceived as lower
in gender role conformity than a gay man who displayed a masculine personality.
Similarly, the gay target who assumed a passive sex role elicited more disgust
and was perceived as lower in gender role conformity than a gay man who assumed
an active sex role. The sexual behavior/disgust relationship was mediated by
perceived gender role conformity.
PMID- 29334021
TI - A Comparison of Training and Competition Demands in Semiprofessional Male
Basketball Players.
AB - PURPOSE: The purpose of this study was to quantify and compare training and
competition demands in basketball. METHODS: Fifteen semiprofessional male
basketball players wore microsensors during physical conditioning training (PCT),
games-based training (GBT), and competition to measure absolute and relative
(.min-1) PlayerLoadTM (PL) and estimated equivalent distance (EED). Internal
responses were calculated using absolute and relative session rating of perceived
exertion (sRPE) and summated heart rate zones (SHRZ). Integrated measures were
calculated as sRPE:PL and SHRZ:PL ratios. RESULTS: PlayerLoad (arbitrary units
[AU]) and EED (m) were statistically significantly (p < .05) higher during PCT
(632 +/- 139 AU, d = 1.36; 5,964 +/- 1,312 m, d = 1.36; 6.50 +/- 0.81 AU.min-1, d
= 2.44; 61.88 +/- 7.22 m.min-1, d = 2.60) and GBT (624 +/- 113 AU, d = 1.54;
5,892 +/- 1,080 m, d = 1.53; 6.10 +/- 0.77 AU.min-1, d = 2.14; 56.76 +/- 6.49
m.min-1, d = 2.22) than they were during competition (449 +/- 118 AU; 3,722 +/-
1474 m; 4.35 +/- 1.09 AU.min-1; 41.01 +/- 10.29 m.min-1). Summated heart rate
zones were statistically significantly (p < .05) higher during PCT (314 +/- 86
AU, d = 1.05; 3.22 +/- 0.50 AU.min-1, d = 1.94) and GBT (334 +/- 79 AU, d = 1.38;
3.19 +/- 0.54 AU.min-1, d = 1.83) than they were during competition (225 +/- 77
AU; 2.17 +/- 0.69 AU.min-1). The ratio of sRPE:PL was statistically significantly
(p < .05) higher during competition (1.58 +/- 0.85) than during PCT (0.98 +/-
0.22, d = 1.44) and GBT (0.91 +/- 0.24, d = 1.90). CONCLUSION: Training demands
exceeded competition demands.
PMID- 29334022
TI - Practitioners' Views on IPV and Its Solutions: An Integrative Literature Review.
AB - There are ongoing debates in the scientific community and in practice settings
about how intimate partner violence (IPV) should be defined and understood and
about how various interventions must be carried out. If these debates are to bear
fruit, however, we must first gain a comprehensive understanding of each
stakeholder's viewpoints on IPV and its solutions. This article seeks to
contribute to this goal by summarizing empirical studies investigating how
practitioners who work with IPV perpetrators understand the problem and its
solutions. Based on an integrative review of the literature, it focuses on how
practitioners define IPV and its causes, how they perceive the perpetrators and
victims, and on the solutions they put forward in order to work against this
social problem. The limitations of our current knowledge are outlined as well as
the implications of this review for IPV debates.
PMID- 29334023
TI - Gender differences in inappropriate use of urinary catheters among hospitalized
older patients.
AB - This study investigated the incidence, rationales, and associated factors of
inappropriate urinary catheter use among hospitalized older patients by gender. A
longitudinal study of 321 patients with urinary catheter was conducted.
Demographic factors, present health factors, urinary catheter factors, and
indications of catheter use were collected. A total of 53.7% of urinary catheter
days were inappropriate. For both men and women, there was no significant
difference in the incidence and common rationales of inappropriate use. Women,
however, have another associated factor with inappropriate use. More tailored
alternatives are needed for women to increase comfort to avoid inappropriate
catheter use.
PMID- 29334024
TI - State of the Evidence: A Systematic Review of Approaches to Reduce Gender-Based
Violence and Support the Empowerment of Adolescent Girls in Humanitarian
Settings.
AB - Adolescent girls are at an increased risk of sexual violence, abuse,
exploitation, and forced or early marriage across humanitarian contexts. In the
past few years, prominent initiatives, organizations, and working groups have
started to highlight the targeted needs and issues facing adolescent girls and
have developed programmatic responses such as safe spaces for adolescent girls to
protect and empower girls and reduce their vulnerabilities to violence or
exploitation. A systematic review of academic and grey literature was conducted
in September 2015 to examine the evidence base for programming that seeks to
reduce violence against adolescent girls in humanitarian contexts. The authors
used a Boolean search procedure to find and review 5830 records from academic
journal databases, resource-hosting websites and relevant organizational
websites. The inclusion criteria left us with three adolescent girl program
evaluations from humanitarian settings to examine, all of which were pre/post
test evaluations that looked at changes in indicators such as social assets, self
esteem, decision making, livelihood skills and financial assets, gender norms,
and feelings of safety. While these three evaluations showed promising results,
overall, this systematic review demonstrates a significant gap in currently
available rigorous research. Evidence is urgently needed to guide programming
decisions to ensure that the emerging programs provide the level and depth of
protection that adolescent girls need in humanitarian settings.
PMID- 29334025
TI - Heart Failure: The Increasing Need for a Focus on Self-Care.
PMID- 29334026
TI - A guide to breast implants for the non-breast specialist.
AB - Breast augmentation is an increasingly popular cosmetic surgery procedure, and
breast implants can also be used in reconstructive surgery following mastectomy.
Problematic breast implants can present to any discipline of medicine, most
frequently to primary care or acute service such as emergency medicine. This
guide aims to inform the non-breast specialist in how to assess and treat common
problems and when referral to specialist services is necessary.
PMID- 29334029
TI - The Relationship Between Childhood Maltreatment and Violence to Others in
Individuals With Psychosis: A Systematic Review and Meta-Analysis.
AB - BACKGROUND: There is a growing body of literature identifying a relationship
between experiences of child abuse and symptoms of psychosis in adults. However,
the impact of this relationship on risk of violence has not been systematically
explored. AIMS: This meta-analysis aimed to consider the influence of childhood
abuse on the risk of violence among individuals with psychosis. METHOD: Five
bibliographic databases and two gray literature resources were systematically
searched to identify quantitative research which measured risk of violence and
experiences of childhood maltreatment in individuals with psychosis. Risk of bias
for each study was assessed under predefined criteria. Logged odds ratios ( OR)
were synthesized quantitatively in a meta-analysis. RESULTS: A total of 6,298
studies were identified, 11 of which were included in the final analysis ( N =
2,215), all studies were of a cross-sectional or case-control design. Individuals
with psychotic illnesses who reported historical child maltreatment were at
approximately twice the risk of perpetrating violence than patients who reported
no early abuse, OR = 2.46, 95% confidence interval (CI) = [1.91, 3.16]. There was
no statistical heterogeneity between main effects (tau = .00; chi2 = 8.87, df =
10, p = .54, I2 = 0%). DISCUSSION: Risk assessments and interventions may benefit
from considering the unique contribution of trauma to violence in this
population. Future research considering the interaction between childhood
experiences and other risk factors for violence in this population, including
specific symptoms of psychosis, would inform the current findings. Findings are
limited by the lack of longitudinal research in this area, and there was some
evidence of publication bias.
PMID- 29334028
TI - Differential diagnosis and management of placental polyp and uterine
arteriovenous malformation: Case reports and review of the literature.
AB - Postpartum uterine bleeding is not uncommon and is caused by a variety of
obstetrical and gynecological disorders, such as retained placenta, dysfunctional
bleeding, and endometrial polyps. Placental polyps and uterine arteriovenous
malformation are disorders often encountered in cases of abnormal uterine
bleeding in the late puerperal period. These patients may experience life
threatening bleeding and require prompt intervention based on the correct
differential diagnosis. The optimal treatments for both diseases differ as
follows: intrauterine curettage or transcervical resection are chosen for
placental polyps, while total abdominal hysterectomy or uterine artery
embolization is preferred for uterine arteriovenous malformation since
intrauterine curettage or transcervical resection has the risk of massive
bleeding. However, since placental polyp and uterine arteriovenous malformation
have similar clinical characteristics, it is important to accurately identify and
differentiate between them to ensure optimal therapy. We report here cases that
were suggestive of placental polyp or uterine arteriovenous malformation. We
discuss the differential diagnoses and treatments for both diseases based on a
literature review and propose a novel algorithm for managing such patients.
PMID- 29334027
TI - Patient-Specific Quality Assurance Using Monte Carlo Dose Calculation and Elekta
Log Files for Prostate Volumetric-Modulated Arc Therapy.
AB - Log file-based methods are attracting increasing interest owing to their ability
to validate volumetric-modulated arc therapy outputs with high resolution in the
leaf and gantry positions and in delivered dose. Cross-validation of these
methods for comparison with measurement-based methods using the ionization
chamber/ArcCHECK-3DVH software (version 3.2.0) under the same conditions of
treatment anatomy and plan enables an efficient evaluation of this method. In
this study, with the purpose of cross-validation, we evaluate the accuracy of a
log file-based method using Elekta log files and an X-ray voxel Monte Carlo dose
calculation technique in the case of leaf misalignment during prostate volumetric
modulated arc therapy. In this study, 10 prostate volumetric-modulated arc
therapy plans were used. Systematic multileaf collimator leaf positional errors
(+/-0.4 and +/-0.8 mm for each single bank) were deliberately introduced into the
optimized plans. Then, the delivered 3-dimensional doses to a phantom with a
certain patient anatomy were estimated by our system. These doses were compared
with the ionization chamber dose and the ArcCHECK-3DVH dose. For the given
phantom and patient anatomy, the estimated dose strongly coincided with the
ionization chamber/ArcCHECK-3DVH dose ( P < .01). In addition, good agreement
between the estimated dose and the ionization chamber/ArcCHECK-3DVH dose was
observed. The dose estimation accuracy of our system, which combines Elekta log
files and X-ray voxel Monte Carlo dose calculation, was evaluated.
PMID- 29334030
TI - Commercial Sexual Exploitation of Youth in the United States: A Qualitative
Systematic Review.
AB - BACKGROUND: Homeless, runaway, and transgender youth are at high risk for
commercial sexual exploitation in the United States. Research examining this
phenomenon is growing but requires synthesis to facilitate its use by
professionals who serve this population. The purpose of this review was to
aggregate the qualitative evidence regarding commercially sexually exploited
youth (CSEY) in the United States. METHODS: The search included published and
unpublished qualitative studies with current or former CSEY who reside in the
United States. RESULTS: There were 19 studies included in the review with a total
of 795 participants. Eight themes were identified and grouped into three broader
categories: experiences that preceded sex work entry, experiences that
facilitated sex work continuation, and experiences that facilitated sex work
exit. CONCLUSIONS: Understanding the barriers and facilitators of commercial
sexual exploitation can inform the development of interventions that address the
needs of CSEY and youth at risk for exploitation. The results of this review
highlight the social and economic influences as well as the role of positive and
negative reinforcements involved in sex work entry, its continuation, and exit.
Needs for services, research, and advocacy are also discussed.
PMID- 29334031
TI - A Profile of Gender-Based Violence Research in Europe: Findings From a Focused
Mapping Review and Synthesis.
AB - This article reports the findings from a new form of review: a focused mapping
review and synthesis. The aim was to create a contemporary, snapshot profile of
the nature and scope of gender-based violence (GBV) studies conducted in Europe.
GBV is one of the most prevalent human rights violations in the world affecting
mainly women and girls. The policy context of GBV in Europe has gathered momentum
in recent years, but we do not have a clear picture of how this relates to
research activity. Thirteen journals were purposively selected on their
likelihood to publish GBV research. All articles published in these journals
during 2015 and meeting our inclusion criteria were retrieved. Data were
extracted according to (1) types of methodologies used, (2) geographical location
of research, and (3) patterns of research activity/interest. Thirty-two articles
met the inclusion criteria. Many titles and abstracts were not explicit about the
gendered nature of the research which made retrieval and analysis difficult. A
range of methodologies were reported, with single-country research conducted more
than international collaborations. Intimate partner violence and sexual abuse
attracted most research interest. No studies explored female genital
mutilation/cutting and only one investigated early and forced marriage. The
findings have implications regarding GBV research in Europe, and we explore them
in relation to relevant European policy. Researchers can help raise the profile
of the gendered nature of most violence-related research by being explicit about
this in their publications. Increasing opportunities for cross-national research
will help address the global nature of GBV. Tackling GBV requires synergy of
empirical evidence and policy to drive the agenda.
PMID- 29334032
TI - Obscure Dichotomy of Early Childhood Trauma in PTSD Versus Attachment Disorders.
AB - There are two competing schools of thoughts involving children who have
experienced early childhood trauma. One posture's nosology focuses on the post
traumatic stress responses; the other focuses on the deviant behaviors that ensue
from pathogenic care in early childhood. This author sought to review the
literature from a holistic perspective, embracing both diagnostic positions.
Seventy-three articles addressing childhood trauma and the ensuing emotional or
behavioral disturbances were evaluated, mostly empirical-including 16 that
specified posttraumatic stress disorder (PTSD), 21 that specified attachment
disorders, and 37 that included potential overlaps between both trauma
derivatives. An additional 138 studies were reviewed but not included herein
because those focused on broader issues. Statistical data, financial and
emotional impacts, and the effects of disrupted attachments were addressed
including both children with secure attachments and those with compromised
attachments. The critical effect of both positive and negative parental responses
was evaluated, as well as correlations or overlaps in the diagnostic criteria and
symptom manifestations of the children and any apparent gaps in the current
research. The literature details that the prognosis and course of treatment vary
significantly between the two etiologies-apparently at least in part due to
possible clinician bias in conceptualizations of the two populations. There are
clear overlaps in the diagnostic criteria that strongly suggest comorbidity
between the disorders, however, which is especially critical to analyze in the
future, since there are solid, empirical, evidence-based treatment protocols for
PTSD, but not for attachment disorders resulting from pathogenic caregiver
maltreatment.
PMID- 29334033
TI - Reappraising and Redirecting Research on the Victim-Offender Overlap.
AB - The strong positive association between offending and victimization, or the
victim-offender overlap, has received considerable amount of research attention
in recent years. Empirical research has made important strides in unpacking the
sources of the phenomenon, but important questions remain unanswered. Ambiguity
surrounds the utility of certain theoretical explanations for the overlap, the
nature of the phenomenon, and the methodological tools used to examine its
etiology. Owing to these knowledge gaps, the scientific meaning of the victim
offender overlap is unclear. Moreover, a number of potentially important
theoretical arguments are rarely subject to empirical testing in this line of
research. The purpose of this article is to use a narrative review methodology to
provide a critical reappraisal of the theoretical, empirical, and methodological
research on the victim-offender overlap and offer directions for ways forward to
develop a more comprehensive understanding of the phenomenon. This review
includes critical analysis of 78 academic publications, along with a table that
summarizes the key findings and conclusions from 18 critical empirical studies
that have contributed to our understanding of the victim-offender overlap. We
offer recommendations for the continued development of theoretical and
methodological tools to better understand this complex phenomenon.
PMID- 29334034
TI - Improved exogenous DNA uptake in bovine spermatozoa and gene expression in
embryos using membrane destabilizing agents in ICSI-SMGT.
AB - Sperm-mediated gene transfer (SMGT) is a simple, fast, and economical
biotechnological tool for producing transgenic animals. However, transgene
expression with this technique in bovine embryos is still inefficient due to low
uptake and binding of exogenous DNA in spermatozoa. The present study evaluated
the effects of sperm membrane destabilization on the binding capacity, location
and quantity of bound exogenous DNA in cryopreserved bovine spermatozoa using
Triton X-100 (TX-100), lysolecithin (LL) and sodium hydroxide (NaOH). Effects of
these treatments were also evaluated by intracytoplasmic sperm injection (ICSI)
SMGT. Results showed that all treatments bound exogenous DNA to spermatozoa
including the control. Spermatozoa treated with different membrane destabilizing
agents bound the exogenous DNA throughout the head and tail of spermatozoa,
compared with the control, in which binding occurred mainly in the post-acrosomal
region and tail. The amount of exogenous DNA bound to spermatozoa was much higher
for the different sperm treatments than the control (P < 0.05), most likely due
to the damage induced by these treatments to the plasma and acrosomal membranes.
Exogenous gene expression in embryos was also improved by these treatments. These
results demonstrated that sperm membrane destabilization could be a novel
strategy in bovine SMGT protocols for the generation of transgenic embryos by
ICSI.
PMID- 29334035
TI - Neural correlates of ostracism in transgender persons living according to their
gender identity: a potential risk marker for psychopathology?
AB - BACKGROUND: Stigmatization in society carries a high risk for development of
psychopathology. Transgender persons are at particularly high risk for such
stigmatization and social rejection by others. However, the neural correlates of
ostracism in this group have not been captured. METHOD: Twenty transgender men
(TM, female-to-male) and 19 transgender women (TW, male-to-female) already living
in their gender identity and 20 cisgender men (CM) and 20 cisgender women (CW)
completed a cyberball task assessing both exclusion and re-inclusion during
functional magnetic resonance imaging (fMRI). RESULTS: During psychosocial stress
between-group differences were found in the dorsal and ventral anterior cingulate
cortex (ACC) and the inferior frontal gyrus (IFG). Patterns were consistent with
sex assigned at birth, i.e. CW showed greater activation in dorsal ACC and IFG
relative to CM and TW. During re-inclusion, transgender persons showed greater
ventral ACC activity relative to CW, possibly indicating persistent feelings of
exclusion. Functional connectivity analyses supported these findings but showed a
particularly altered functional connectivity between ACC and lateral prefrontal
cortex in TM, which may suggest reduced emotional regulation to the ostracism
experience in this group. Depressive symptoms or hormonal levels were not
associated with these findings. CONCLUSION: The results bear implications for the
role of social exclusion in development of mental health problems in socially
marginalized groups.
PMID- 29334036
TI - Short-term storage of the oocytes affects the ploidy status in the yellowtail
tetra Astyanax altiparanae.
AB - In fish, many factors can affect reproduction during in vitro fertilization,
therefore determination of the factors that affect affecting gamete quality is
needed. However, few studies have focused on gamete quality and the ploidy
status. This study was conducted to elucidate whether oocyte storage can affect
ploidy status, survival, and embryo viability in the characid species Astyanax
altiparanae. Oocytes were stored in Dulbecco's phosphate-buffered saline (PBS) at
26 degrees C, then aliquots were fertilized immediately after extrusion (control)
and also after 60, 120, 180, and 240 min of storage. Fertilization and hatching
rates were measured, and the developmental stages were analyzed at each stage
before describing the main abnormalities. Ploidy status was analyzed by flow
cytometry and blood smear. In the control group, 100% of the samples were
diploid. After treatment for 60 min, 95.56 +/- 4.44% samples were diploid and
4.44 +/- 4.44% were triploid. After 120 min, 94.44 +/- 9.62% of the samples was
diploid and 5.56 +/- 5.56% were triploid; 100% of the samples were diploid after
180 min and, after 240 min, there was no survival. In other treatments, the
highest percentage of hatching was after 60 min (88.93 +/- 5.15%; P = 0.015), and
treatment with 180 min storage resulted in the highest percentage of abnormal
larvae (95.76 +/- 12.67%; P = 0.012). These results show that oocyte storage can
affect ploidy status and may be an interesting parameter for analysis in studies
on chromosome set manipulation and micromanipulation.
PMID- 29334037
TI - Improvement in the Prognosis of Cerebral Venous Sinus Thrombosis over a 22-Year
Period.
AB - BACKGROUND: Cerebral venous thrombosis is a rare cause of stroke, with a number
of well-defined risk factors. However, there exist few studies that describe
trends in the prognosis of this disease over time. METHODS: A retrospective study
was performed on patients diagnosed with cerebral venous thrombosis at the
University of Alberta Hospital during two time periods: 1988-1998 (21 patients)
and 1999-2009 (40 patients). Signs and symptoms, risk factors, imaging findings,
etiologies, treatment modalities, and status at discharge were examined. RESULTS:
Headache, nausea and vomiting, focal motor deficit, and seizure were the most
common signs and symptoms, and active hormonal contraception was the most
commonly identified risk factor between the two cohorts. Hematoma and hyperdense
sinuses were the most commonly identified CT findings between groups.
Thrombophilia and the use of hormonal contraception were the most frequently
identified etiologies between the two cohorts. Treatment was similar, with the
majority of patients in both cohorts receiving unfractionated heparin as first
line therapy. Patients in the 1999-2009 cohort were significantly less likely to
have a severe deficit or be dead at discharge (odds ratio [OR]=0.178; 95%
confidence interval [CI 95%]=0.051, 0.625) and were more likely to have a
favorable modified Rankin Scale score of 0 or 1 at discharge (OR=7.98; CI
95%=1.79, 35.71). CONCLUSIONS: Our data indicate a reduction in severe residual
symptoms at discharge and improved functional status at discharge for patients
presenting with cerebral venous thrombosis from 1999 to 2009, as compared with
1988-1998.
PMID- 29334038
TI - Robotic-Assisted and Image-Guided MRI-Compatible Stereoelectroencephalography.
AB - BACKGROUND: Stereoelectroencephalography has been in regular use at the Montreal
Neurological Institute since 1972. The technique has been in constant evolution
to incorporate advances in materials, imaging, and robotics technology. MRI
compatible electrodes were introduced in 2007 and robotics in 2011. Here we
report on the technique, safety, and advantages of our current method of
stereoelectroencephalography implantation. METHODS: We retrospectively reviewed
all patients who underwent stereoelectroencephalography by the senior author.
Technical, clinical, and radiological complications, and postimplantation
outcomes were analyzed. Only patients implanted with MRI-compatible electrodes
were included to review MRI abnormalities with electrodes in situ. RESULTS: A
total of 53 patients were implanted with 550 electrodes (average=10.4 per
patient), for an average duration of 14.6 days. There was no mortality,
infection, or new neurologic deficit. Two patients had a superficial screw plunge
without clinical consequence. Four patients demonstrated asymptomatic MRI
abnormalities (7.54% per patient, or 0.72% per electrode). MRI with electrodes in
situ was used for neuronavigation in all 29 who underwent resection and yielded a
histopathological diagnosis of focal cortical dysplasia in 15 MRI-negative
patients. CONCLUSIONS: The technique of stereoelectroencephalography described
here was associated with no clinical morbidity although not without technical
complications or radiologic (MRI) abnormalities. We should therefore remain
vigilant in refining the technique and minimizing the number of electrodes
required to answer a well-developed hypothesis regarding the epileptogenic zone.
The use of MRI-compatible electrodes allowed neuronavigation using the images
with the electrodes in situ, which was useful to tailor the eventual definitive
resection and in localizing MRI-negative lesions.
PMID- 29334039
TI - Refractory Epilepsy: The Role of Positron Emission Tomography.
AB - RATIONALE: Presurgical localization of the epileptogenic focus is critical to
successful surgery. Traditionally, localization of the epileptogenic focus
depends on seizure semiology, scalp video-electroencephalography (vEEG), magnetic
resonance imaging (MRI), neuropsychological assessment, and, when needed,
intracranial EEG (iEEG). We aimed to explore the role of positron emission
tomography (PET) in the presurgical evaluation of patients with refractory
epilepsy. METHODS: A retrospective review was conducted on patients from London
Health Sciences Centre (London, Ontario) with refractory epilepsy who underwent
PET from September of 2011 to April of 2016. The accuracy of epileptogenic focus
localization was compared between different investigative modalities (MRI, vEEG,
iEEG, PET), and the outcomes were documented, including seizure freedom after
surgical resection, improvement of seizure frequency, guidance for further
investigations, and exclusion of patients from further evaluation. Patients who
underwent surgery were followed up at 3 months and onward. RESULTS: We identified
62 patients with refractory epilepsy who underwent PET. The mean age was 34 years
(range=20-68). A total of 36 had concordant PET and vEEG findings: 6 had surgical
resection and either became seizure-free (29.4%) or had improvement in seizure
frequency (5.9%) at 3 months; 11 had surgical resection and either became seizure
free (29.4%) or had improvement in seizure frequency (35.3%) at 3 months, but
required iEEG for final verification. CONCLUSIONS: PET has an important role in
presurgical evaluation of patients with refractory epilepsy. It may allow
resection of the epileptogenic focus without the need for iEEG, guiding
intracranial electrode placement for further localization of the epileptogenic
focus, or exclusion of patients from further evaluation.
PMID- 29334040
TI - Botulinum Toxin Type A for Pain in Advanced Parkinson's Disease.
AB - Background and Objective Pain is a frequent symptom in Parkinson's disease (PD),
and the therapeutic alternatives are scarce. The goal of this trial was to
measure the effects of botulinum toxin type A (BTXA) in the treatment of limb
pain in advanced PD. Methods A randomized double-blind crossover versus placebo
study of BTXA for limb pain in advanced Parkinson's disease was conducted.
Subjects received individualized BTXA/placebo dosing per pain distribution in
limbs. The primary outcome was a measure of change in global pain on a numeric
rating scale (NRS) at 4 and 12 weeks postinjection and on a visual analogue scale
12 weeks after treatment. Secondary outcomes included the percentage of
responders, physician-rated clinical global impressions, MDS-UPDRS and PDQ-39
scores, and adverse events. Results A total of 12 subjects completed the trial.
Treatment with BTXA (average dose=241.66 U) produced a significant reduction in
NRS score 4 weeks after the injections (-1.75 points, range from -3 to 7,
p=0.033). However, there was no significant difference compared to placebo
(p=0.70). Participants with dystonic pain showed a greater reduction in NRS score
after 4 weeks when treated with BTXA (2.66 points vs. 0.75 for placebo). There
were no significant differences for any of the secondary outcomes or significant
adverse events. Conclusions Targeted BTXA injections were safe in patients with
limb pain and advanced PD; however, the present study failed to show a
significant effect when compared to placebo. Further studies may be focused on
evaluating the effect of BTXA particularly in dystonic pain.
PMID- 29334041
TI - Autoantibodies to Low-Density Lipoprotein Receptor-Related Protein 4 in Double
Seronegative Myasthenia Gravis: A Systematic Review.
AB - BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular
junction in which a clinical diagnosis may be confirmed with serological testing.
The most common autoantibodies used to support a diagnosis of MG are anti
acetylcholine receptor antibodies and anti-muscle-specific tyrosine kinase
antibodies. In cases in which both of these autoantibodies are negative (termed
double-seronegative [dSNMG]), other autoantibodies such as low-density
lipoprotein receptor-related protein 4 (LRP4) may be used to aid in diagnosis.
METHODS: We have undertaken a systematic literature review to identify studies
that have assessed the frequency of anti-LRP4 antibodies in dSNMG patients and
the characteristics of anti-LRP4+ dSNMG patients (epidemiology, clinical
features, electromyographic findings, or management). PubMed, EMBASE, Medline,
and Scopus were searched on January 14, 2017, using the medical subject headings
"myasthenia gravis" and "low-density lipoprotein receptor-related protein 4" or
"LRP4." RESULTS: The initial search identified 367 articles. Fourteen
publications met the inclusion criteria. There were ten cross-sectional research
studies, three were case series, and one was a case report. The majority of
studies were limited by small sample sizes of LRP4+ dSNMG. There has been a wide
range of frequencies of anti-LRP4 antibodies detected in different MG patient
populations, some involving different laboratory techniques. CONCLUSIONS: LRP4+
dSNMG is more likely than LRP4- dSNMG to have a younger onset of disease and
occur in females. LRP4+ dSNMG most often is mild in severity and often involves
isolated ocular weakness. It typically responds well to pyridostigmine or
prednisone.
PMID- 29334042
TI - Orbital Myositis: An Underrecognized Clinical Syndrome with a Need of Management
Guidelines.
PMID- 29334043
TI - A Tribute to James Parkinson.
AB - Exactly 200 years ago, the London surgeon-apothecary James Parkinson (1755-1824)
published a 66-page-long booklet entitled An Essay on the Shaking Palsy, which
contains the first clear clinical description of the shaking palsy or paralysis
agitans, which we now refer to as Parkinson's disease. However, the value of this
essay was not fully recognized during Parkinson's lifetime, which spanned the
American Revolution, the French Revolution, and the Napoleonic Wars. James
Parkinson was one of the most singular figures of his time and place. He was
successively or concomitantly a virulent political activist, a popular medical
writer, a scholarly medical contributor, a highly appreciated parish doctor, a
prominent amateur chemist, a devoted madhouse doctor, and a renowned
paleontologist. It is that branch of geology that brought Parkinson fame during
his lifetime. He was an insatiable collector of fossils, minerals, and shells
that came to form the core of the museum that he set out at his home in
Shoreditch, England. These specimens are beautifully illustrated in his Organic
Remains of a Former World (1804-1811), a three-volume treatise that rapidly
became a standard paleontology textbook. Parkinson was a founding member of the
Geological Society of London, and in recognition of his contribution to the
nascent field of paleontology his name was given to many fossils, particularly
ammonites (e.g. Nautilus parkinsoni). Hence, we owe much to Mr. Parkinson, the
Paleontologist, as he used to be referred to after his death, for such a vast and
multifaceted contribution to natural science and medicine.
PMID- 29334044
TI - Gene-environment interplay in the etiology of psychosis.
AB - Schizophrenia and other types of psychosis incur suffering, high health care
costs and loss of human potential, due to the combination of early onset and poor
response to treatment. Our ability to prevent or cure psychosis depends on
knowledge of causal mechanisms. Molecular genetic studies show that thousands of
common and rare variants contribute to the genetic risk for psychosis.
Epidemiological studies have identified many environmental factors associated
with increased risk of psychosis. However, no single genetic or environmental
factor is sufficient to cause psychosis on its own. The risk of developing
psychosis increases with the accumulation of many genetic risk variants and
exposures to multiple adverse environmental factors. Additionally, the impact of
environmental exposures likely depends on genetic factors, through gene
environment interactions. Only a few specific gene-environment combinations that
lead to increased risk of psychosis have been identified to date. An example of
replicable gene-environment interaction is a common polymorphism in the AKT1 gene
that makes its carriers sensitive to developing psychosis with regular cannabis
use. A synthesis of results from twin studies, molecular genetics, and
epidemiological research outlines the many genetic and environmental factors
contributing to psychosis. The interplay between these factors needs to be
considered to draw a complete picture of etiology. To reach a more complete
explanation of psychosis that can inform preventive strategies, future research
should focus on longitudinal assessments of multiple environmental exposures
within large, genotyped cohorts beginning early in life.
PMID- 29334045
TI - Development of a patient experience questionnaire to improve lifestyle services
in primary care.
AB - : Aim We developed a self-report tool to assess patients' experiences with
lifestyle services in team-based primary care and pilot tested the questionnaire
as part of a lifestyle intervention study to reverse metabolic syndrome.
BACKGROUND: Older client satisfaction questionnaires have been generally
inadequate for quality improvement purposes, as they have been focused mainly on
interpersonal skills of providers and/or in the context of one disease. New
approaches to assessing the patient experience of lifestyle programs in primary
care are needed and could inform quality improvement efforts over time. METHODS:
The first phase in developing the questionnaire involved a group-administered
questionnaire distributed to 38 healthcare providers in five groups to prioritize
variables to include in the survey. Concepts were taken from a previous review of
available questionnaires assessing primary care services. The draft questionnaire
was reviewed by 11 participants from a lifestyle program using think-aloud
cognitive interviewing techniques. The modified self-administered questionnaire
(paper and online versions) was then pilot tested with 164 recipients of a
nutrition and physical activity intervention program. Findings Providers ranked
the top variables to include in the questionnaire as: 'trust,' 'general
communication,' 'first-contact accessibility,' 'whole-person care,' and
'respectfulness.' After cognitive interviewing and revisions, 21 multiple choice
and two open-ended questions were used for pilot testing. Pilot testing
identified additional minor wording changes that were needed for clarity, a
decreased number of questions for redundant concepts, and decreased options for
ceiling effects, resulting in 20 multiple choice and one open-ended question.
CONCLUSIONS: The modified self-administered patient experience questionnaire to
assess lifestyle services in primary care has undergone rigorous development.
Further validation is needed. The assessment of patient experience of lifestyle
programs can be used to supplement other data to assess the overall effectiveness
of such programs.
PMID- 29334046
TI - Antimicrobial Activities of Novel Bis-Piperidinium Compounds.
AB - The antimicrobial activity of two new series of bis-piperidinium compounds with
alkyl chains of different lengths against bacterial (Escherichia coli,
Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis) and fungal
strains (Aspergillus flavus, Aspergillus niger, Rhodolorula rubera, Lipomyces
lopofera and Candida albicans), are described. Antimicrobial activities of the
synthesized compounds were compared to that of dodecyltrimethylammonium chloride.
Bis-piperidinium salts possessing 12-16 carbon side chains showed better
antimicrobial properties as compared to the standard dodecyltrimethylammonium
chloride.
PMID- 29334047
TI - Partial Characterization of Bacteriocin Produced by Halotolerant Pediococcus
acidilactici Strain QC38 Isolated from Traditional Cotija Cheese.
AB - During a screening of lactic acid bacteria producing bacteriocin from Cotija
cheese, the strain QC38 was isolated. Based on the 16S rRNA gene nucleotide
sequencing (516 pb accession no KJ210322) and phylogenetic analysis, the isolate
was identified as Pediococcus acidilactici. Neutralized cell-free supernatant was
tested for antimicrobial activity against 17 Gram-negative and Gram-positive
pathogens. Growth inhibition was achieved against Listeria monocytogenes
(supplier or indication or source), Staphylococcus aureus, Vibrio vulnificus,
Vibrio cholerae O1 Ogawa, Vibrio cholerae NO 01 and Salmonella enterica subsp.
Enterica serovar Typhimurium. Bacteriocin-like substance, after heating at 121
degrees C for 15 min it remained stable and its antimicrobial activity was
observed at pH ranging from 1.0 to 10.0 but inactivated by alpha-chymotrypsin and
proteinase K. Strain QC38 was able to grow in 1-9% NaCl concentration. The plate
overlay assay showed an approximate size of bacteriocin-like substance between
3.4 and 6.5 kDa. P. acidilactici QC38 harboured a plasmid that contains a gene
for a pediocin (PA-1).
PMID- 29334048
TI - Use of the Real Time xCelligence System for Purposes of Medical Microbiology.
AB - Roche's xCelligence impedance-measuring instrument is one of a few commercially
available systems of such type. According to the best knowledge of authors,
instrument was tested so far only for eukaryotic cell research. The aim of this
work was to estimate xCELLigence suitability for the microbiological tests,
including (i) measurement of morphological changes in eukaryotic cells as a
result of bacterial toxin activity, (ii) measurement of bacterial biofilm
formation and (iii) impact of antiseptics on the biofilm structure. To test the
infuence of bacterial LT enterotoxin on eukaryotic cell lines, Chinese Hamster
Ovary (CHO) cell line and reference strain Escherichia coli ATTC 35401 were used.
To investigate Roche's instrument ability to measure biofilm formation and impact
of antiseptics on its development, Staphylococcus aureus ATTC6538 reference
strain was used. The data generated during the experiments indicate excellent
ability of xCelligence instrument to detect cytopathic effect caused by bacterial
LT endotoxin and to detect staphylococcal biofilm formation. However,
interpretation of the results obtained during real-time measurement of
antiseptic's bactericidal activity against staphylococcal biofilm, caused many
difficulties. xCelligence instrument can be used for real-time monitoring of
morphological changes in CHO cells treated with bacterial LT enterotoxin and for
real-time measurement of staphylococcal biofilm formation in vitro. Further
investigation is necessary to confirm suitability of system to analyze
antiseptic's antimicrobial activity against biofilm in vitro.
PMID- 29334049
TI - Phylogenetic Analysis Based on 16S rRNA Gene of a Thermophilic Protease-Secreting
Bacillus gelatini-TPNK-3 Isolate from Kiteezi Landfill, Uganda.
AB - A thermophilic protease-secreting bacterial isolate, TPNK-3, from Kiteezi
landfill, is an aerobic Gram-positive spore-forming bacterium with rod-shaped
cells (3.28 MUm long and 0.45 MUm wide). Optimal growth was observed at 55
degrees C and pH of 7.0, and the isolate tolerates up to 5% (w/v) NaCl, exhibits
extracellular amylolytic, cellulolytic and caseinolytic activities, utilizes a
range of carbon and nitrogen sources and has a GC content of 45 mol%. The 16S
rRNA gene sequence analysis showed that the studied bacterium belongs to the
genus Bacillus, and closest to Bacillus gelatini (>99.9%). Consequently, isolate
TPNK3 is tentatively described as Bacillus gelatini strain TPNK3.
PMID- 29334050
TI - Enzymatic Activity of Prototheca zopfii Strains Isolated from Cows with Mastitis.
AB - Bovine mastitis caused by Prototheca spp. can be a disease of high significance
because of economic losses and the potential risk to public health. The aim of
our study was to evaluate enzymatic activity of Prototheca zopfii. For this
study, we used 15 P. zopfii strains previously isolated from cows with clinical
and subclinical mastitis in Poland. We determined enzymatic profile of Prototheca
species using the API ZYM system. Of the enzymatic activities detected during the
study, acid phosphatase, leucine arylamidase, naphthol-as-bi-phosphohydrolase,
esterase, lipase esterase, valine arylamidase, alkaline phosphatase, and lipase
C14 were found in high percentage of strains.
PMID- 29334051
TI - Characterization of a Highly Enriched Microbial Consortium Reductively
Dechlorinating 2,3-Dichlorophenol and 2,4,6-Trichlorophenol and the Corresponding
cprA Genes from River Sediment.
AB - Anaerobic reductive dechlorination of 2,3-dichlorophenol (2,3DCP) and 2,4,6
trichlorophenol (2,4,6TCP) was investigated in microcosms from River Nile
sediment. A stable sediment-free anaerobic microbial consortium reductively
dechlorinating 2,3DCP and 2,4,6TCP was established. Defined sediment-free
cultures showing stable dechlorination were restricted to ortho chlorine when
enriched with hydrogen as the electron donor, acetate as the carbon source, and
either 2,3-DCP or 2,4,6-TCP as electron acceptors. When acetate, formate, or
pyruvate were used as electron donors, dechlorination activity was lost. Only
lactate can replace dihydrogen as an electron donor. However, the dechlorination
potential was decreased after successive transfers. To reveal chlororespiring
species, the microbial community structure of chlorophenol-reductive
dechlorinating enrichment cultures was analyzed by PCR-denaturing gradient gel
electrophoresis (DGGE) of 16S rRNA gene fragments. Eight dominant bacteria were
detected in the dechlorinating microcosms including members of the genera
Citrobacter, Geobacter, Pseudomonas, Desulfitobacterium, Desulfovibrio and
Clostridium. Highly enriched dechlorinating cultures were dominated by four
bacterial species belonging to the genera Pseudomonas, Desulfitobacterium, and
Clostridium. Desulfitobacterium represented the major fraction in DGGE profiles
indicating its importance in dechlorination activity, which was further confirmed
by its absence resulting in complete loss of dechlorination. Reductive
dechlorination was confirmed by the stoichiometric dechlorination of 2,3DCP and
2,4,6TCP to metabolites with less chloride groups and by the detection of
chlorophenol RD cprA gene fragments in dechlorinating cultures. PCR amplified
cprA gene fragments were cloned and sequenced and found to cluster with the
cprA/pceA type genes of Dehalobacter restrictus.
PMID- 29334052
TI - The Effect of a Small Conotoxin-Like ctx Gene from Autographa californica Nuclear
Polyhedrosis Virus (AcMNPV) on Insect Hemolymph Melanization.
AB - The conotoxin-like (ctx) gene encodes a small cysteine-rich polypeptide in
various baculoviruses. Previous research has demonstrated that the product of the
ctx gene could be purified from insect cells infected by Autographa californica
nuclear polyhedrosis virus (AcMNPV), but its function was unknown. In this paper,
we compared the conserved cysteine motif structure (CX3GX2CX5CCX3CX6C) of the ctx
gene in baculoviruses and generated recombinant Bombyx mori nuclear polyhedrosis
virus (BmNPV) with the BmNPV bacmid system. The recombinant BmNPV contained the
ctx gene from AcMNPV or a fusion gene of ctx with eGFP, respectively.
Fluorescence in CTX-eGFP-positive cells was mainly observed on the cell membrane.
To gain insight into CTX function, two methods were used to elucidate the affect
CTX had on hemolymph melanization in vivo and in vitro in insect larvae and
pupae. The results indicated that CTX abrogates hemolymph melanization; however,
the mechanisms require further evaluation.
PMID- 29334053
TI - Complex Biochemical Analysis of Fruiting Bodies from Newly Isolated Polish
Flammulina velutipes Strains.
AB - The present study examined Polish strains of Flamulina velutipes as a potential
source of nutraceuticals and found that their nutritional value is dependent on
the fruiting bodies gathering time. To prove the above hypothesis protein,
carbohydrate and phenolic substances concentration were determined. Moreover,
catalase, superoxide dismutase, cellobiose dehydrogenase activities were assayed.
In order to prove the healing properties of Enoki fruiting bodies the obtained
extracts were tested for antioxidant and bacteriostatic abilities. We have proved
that Polish F. velutipes fruiting bodies may be a rich source of antioxidants and
that they are capable of inhibiting Staphylococcus aureus growth.
PMID- 29334054
TI - Candida albicans Denture Biofilm and its Clinical Significance.
AB - Fungi belonging to Candida genus, especially C. albicans play an important role
in microflora of oral cavity. Microbial colonisation process taking place within
oral cavity is inseparably related to formation of multispecies biofilm, i.e.
dental and denture plaque. A mature fungal biofilm is a heterogeneous three
dimensional dense conglomeration of mixture of different morphological forms:
blastospores, germ tubes, pseudohyphae and hyphae surrounded by the extracellular
polymeric matrix. Composition and specific properties of substratum, saliva and
yeasts as well as multiple intricate interactions between all of them influence
the ability of Candida spp. isolates to adhere and colonise both natural and
artificial surfaces, followed by biofilm formation. Obviously, specific complex
host-pathogen interactions also should not be neglected. A lot of additional
factors like poor oral and denture hygiene, low pH under prosthesis, sufficient
concentration of sugar and iron or antibody titres influence Candida adhesion and
colonisation of acrylic resin base. C. albicans is capable of inducing a variety
of superficial diseases of the oral mucosa. The most common clinical form of oral
candidal infection related to biofilm formation affecting a great deal of denture
wearers is denture-associated stomatitis, also known as chronic atrophic
candidiasis or erythemateous candidasis. Development of C. albicans biofilm on a
denture surface constitutes a difficult and hard to resolve problem which may
concern every single prosthesis-wearer. Thus, careful oral and denture hygiene is
highly recommended for the population of artificial teeth wearers.
PMID- 29334055
TI - Endophytic Detection in Selected European Herbal Plants.
AB - A total of 181 cultivable endophytic bacterial isolates were collected from stems
of 13 species of herbs inhabiting Europe (Poland): Chelidonium majus L., Elymus
repens L., Erigeron annuus L., Euphrasia rostkoviana Hayne, Foeniculum vulgare
L., Geranium pratense L., Humulus lupulus L., Matricaria chamomilla L., Mentha
arvensis L., Papaver rhoeas L., Rosmarinus officinalis L., Solidago gigantea L.
and Vinca minor L. The isolates were screened for their antifungal activity and
fifty three were found to inhibit fungal growth. Of these, five had strong
antifungal properties. These selected isolates were identified as: Pseudomonas
azotoformans, P. cedrina, Bacillus subtilis group and Erwinia persicina.
PMID- 29334056
TI - Concept for Development of Expert Computer Program for Identification of
Filamentous Fungi.
AB - An expert program has been developed for users working in industrial laboratories
who are not experts in the identification of filamentous fungi. The database of
morphological growth features currently contains 12 species from the genera
Aspergillus and Penicillium grown under standard conditions. The identification
algorithm implemented in the database takes into account the reliability of
users, which can vary over a wide range depending on the identification feature.
The reliability of users was estimated on the basis of a questionnaire survey
conducted among 27 non-experts, as the likelihood of a response consistent with
the assessment of experts. The program works through comparative analysis of
features of the fungus being identified with the expert-developed database and
selection of the most likely species among the species represented by reference
strains. The expert program reduces subjective mistakes and may be extended to
include further fungal species and genera; it can also be supplemented with
chemotaxonomic, genetic and other data.
PMID- 29334057
TI - Characterization of Rhizobial Bacteria Nodulating Astragalus corrugatus and
Hippocrepis areolata in Tunisian Arid Soils.
AB - Fifty seven bacterial isolates from root nodules of two spontaneous legumes
(Astragalus corrugatus and Hippocrepis areolata) growing in the arid areas of
Tunisia were characterized by phenotypic features, 16S rDNA PCR-RFLP and 16S rRNA
gene sequencing. Phenotypically, our results indicate that A. corrugatus and H.
areolata isolates showed heterogenic responses to the different phenotypic
features. All isolates were acid producers, fast growers and all of them used
different compounds as sole carbon and nitrogen source. The majority of isolate
grew at pHs between 6 and 9, at temperatures up to 40 degrees C and tolerated 3%
NaCl concentrations. Phylogenetically, the new isolates were affiliated to four
genera Sinorhizobium, Rhizobium, Mesorhizobium and Agrobacterium. About 73% of
the isolates were species within the genera Sinorhizobium and Rhizobium. The
isolates which failed to nodulate their host plants of origin were associated to
Agrobacterium genus (three isolates).
PMID- 29334058
TI - Prevalence of Biofilm Formation and Wide Distribution of Virulence Associated
Genes among Vibrio spp. Strains Isolated from the Monastir Lagoon, Tunisia.
AB - In the current study, 65 Vibrio spp. were isolated from the Monastir lagoon
water, were characterized phenotypically and genotypically. In addition, we
looked for the presence of three Vibrio parahaemolyticus virulence genes (tlh,
trh and tdh) and ten Vibrio cholerae virulence genes (ctxA, vpi, zot, ace, toxR,
toxT, tosS, toxRS, tcpA and cpP). We also investigated the antibiotic
susceptibilities and the adherence ability of the identified strains to abiotic
material and to biotic surfaces. The cytotoxicity activity against HeLa and Vero
cell lines were also carried out for all tested strains. All Vibrio isolates were
identified to the species level and produced several hydrolytic exoenzymes. The
results also revealed that all strains were expressing high rates of resistance
to tested antibiotics. The minimum inhibitory concentration (MIC) values showed
that tetracycline and chloramphenicol were the most effective antibiotics against
the tested bacteria. Vibrio alginolyticus and V. cholerae species were the most
adhesive strains to both biotic and abiotic surfaces. Besides, V. alginolyticus
isolates has the high levels of recombination of genes encoding V. cholerae and
V. parahaemolyticus virulence factors. In vitro cytotoxic activities of several
Vibrio extracellular product were also observed among HeLa and Vero cells.
PMID- 29334059
TI - Molecular Characterization of Shiga Toxin-Producing Escherichia coli Strains
Isolated in Poland.
AB - Shiga toxin-producing Escherichia coli (STEC) strains also called verotoxin
producing E. coli (VTEC) represent one of the most important groups of food-borne
pathogens that can cause several human diseases such as hemorrhagic colitis (HC)
and hemolytic - uremic syndrome (HUS) worldwide. The ability of STEC strains to
cause disease is associated with the presence of wide range of identified and
putative virulence factors including those encoding Shiga toxin. In this study,
we examined the distribution of various virulence determinants among STEC strains
isolated in Poland from different sources. A total of 71 Shiga toxin-producing E.
coli strains isolated from human, cattle and food over the years 1996-2010 were
characterized by microarray and PCR detection of virulence genes. As stx1a
subtype was present in all of the tested Shiga toxin 1 producing E. coli strains,
a greater diversity of subtypes was found in the gene stx2, which occurred in
five subtypes: stx2a, stx2b, stx2c, stx2d, stx2g. Among STEC O157 strains we
observed conserved core set of 14 virulence factors, stable in bacteria genome at
long intervals of time. There was one cattle STEC isolate which possessed
verotoxin gene as well as sta1 gene encoded heat-stable enterotoxin STIa
characteristic for enterotoxigenic E. coli. To the best of our knowledge, this is
the first comprehensive analysis of virulence gene profiles identified in STEC
strains isolated from human, cattle and food in Poland. The results obtained
using microarrays technology confirmed high effectiveness of this method in
determining STEC virulotypes which provides data suitable for molecular risk
assessment of the potential virulence of this bacteria. virulence factors
including those encoding Shiga toxin. In this study, we examined the distribution
of various virulence determinants among STEC strains isolated in Poland from
different sources. A total of 71 Shiga toxin-producing E. coli strains isolated
from human, cattle and food over the years 1996-2010 were characterized by
microarray and PCR detection of virulence genes. As stx1a subtype was present in
all of the tested Shiga toxin 1 producing E. coli strains, a greater diversity of
subtypes was found in the gene stx2, which occurred in five subtypes: stx2a,
stx2b, stx2c, stx2d, stx2g. Among STEC O157 strains we observed conserved core
set of 14 virulence factors, stable in bacteria genome at long intervals of time.
There was one cattle STEC isolate which possessed verotoxin gene as well as sta1
gene encoded heat-stable enterotoxin STIa characteristic for enterotoxigenic E.
coli. To the best of our knowledge, this is the first comprehensive analysis of
virulence gene profiles identified in STEC strains isolated from human, cattle
and food in Poland. The results obtained using microarrays technology confirmed
high effectiveness of this method in determining STEC virulotypes which provides
data suitable for molecular risk assessment of the potential virulence of this
bacteria.
PMID- 29334060
TI - Nonspecific Bacterial Flora Isolated from the Body Surface and Inside Ixodes
ricinus Ticks.
AB - Ixodes ricinus and other representatives of the order Ixodida are vectors of
typical pathogens: Borrelia burgdorferi sensu lato, Anaplasma phagocytophilium,
Babesia spp., a tick-borne encephalitis virus, and other microorganisms which are
important from a medical and veterinary point of view. The presented study
focuses on the verification of nonspecific bacterial flora of I. ricinus. We
analyzed ticks collected in a forest region in Silesia, an industrial district in
Poland. Methods of classical microbiology and biochemical assays (API 20 NE test,
API Staph test and MICRONAUT System) were used for isolation and identification
of microorganisms living on the body surface of I. ricinus and inside ticks. The
results show the presence of various bacteria on the surface and inside ticks'
bodies. During the study, we isolated Acinetobacter lwoffi, Pseudomonas
fluorescens, Aeromonas hydrophila, Achromobacter denitrificans, Alcaligenes
faecalis, Stenotrophomonas maltophilia, Pseudomonas oryzihabitans, Micrococcus
spp., Kocuria varians, Staphylococcus lentus, Kocuria kristinae, Streptococcus
pneumoniae, Rhizobium radiobacter, Staphylococcus xylosus. Majority of the
isolated species are non-pathogenic environmental microorganisms, but some of the
isolated bacterial strains could cause severe infections.
PMID- 29334061
TI - The Effect of Local Platelet Rich Plasma Therapy on the Composition of Bacterial
Flora in Chronic Venous Leg Ulcer.
AB - Microbial colonisation of chronic venous ulcers and synergism between bacterial
species slow down the healing process. The study aimed at performing qualitative
analysis of microbial flora in venous leg ulcers treated with platelet rich
plasma (PRP). Twenty two women and twelve men aged 47-90 years were treated with
PRP at our department between 2012 and 2015. Ulcer cultures collected before and
after PRP therapy yielded 83 and 110 microbial isolates, respectively, of Gram
positive, Gram negative bacteria and candida. Pseudomonas aueruginosa and
Staphylococcus aureus were the most common pre- and post-treatment isolates. PRP
therapy and increased the variety of microbial flora.
PMID- 29334062
TI - The Role of Staphylococcus aureus in Secondary Infections in Patients with Atopic
Dermatitis (AD).
AB - Staphylococcus aureus colonizes the mucous membrane of the nasal vestibule of a
significant number of healthy people. These microorganisms are opportunistic
pathogens, that in favorable conditions, may cause infections of various course,
location or manifestation. Secondary infections emerge in cases when other risk
factors contribute to such a change. One of the diseases during which S. aureus
changes its saprophytic character to a pathogenic one is atopic dermatitis (AD),
an allergic skin condition of a chronic and recurrent nature. Patients with AD
are highly predisposed to secondary staphylococcal infections due to active S.
aureus colonization of the stratum corneum, damage of the skin barrier or a
defective immune response. Microorganisms present in skin lesions destroy the
tissue by secreting enzymes and toxins, and additionally stimulate secondary
allergic reactions. The toxins secreted by strains of S. aureus also act as
superantigens and penetrate the skin barrier contributing to a chronic
inflammation of the atopic skin lesions. The S. aureus species also releases
proinflammatory proteins, including enzymes that cause tissue damage. When
initiating treatment it is particularly important to properly assess that the
onset of the secondary bacterial infection is caused by S. aureus and thus
justifying the inclusion of antibiotic therapy. Depending on the severity and
extent of the staphylococcal infection, topical antibiotics are used, usually
mupirocin or fusidic acid, or general antibiotic treatment is introduced. Another
therapeutic strategy without antibiotics has given a positive effect in patients.
PMID- 29334063
TI - Penicillin Resistance in Enterococcus faecalis: Molecular Determinants and
Epidemiology.
AB - Enterococcus faecalis plays a significant role in hospital-acquired infections
(HAIs), and combination of penicillin with aminoglycoside is important in therapy
of invasive HAIs. Penicillin resistance in this organism is due to modification
of the drug target, penicillin-binding protein (PBP5), its overproduction and
expression of beta-lactamase. Although rare, this phenotype is often associated
with multi-resistant high-risk enterococcal clonal complexes (HiRECCs), such as
CC2 and CC9 which may promote its spread in the near future.
PMID- 29334064
TI - Distribution and Identification of Endophytic Streptomyces Species from Schima
wallichii as Potential Biocontrol Agents against Fungal Plant Pathogens.
AB - The prospective of endophytic microorganisms allied with medicinal plants is
disproportionally large compared to those in other biomes. The use of
antagonistic microorganisms to control devastating fungal pathogens is an
attractive and eco-friendly substitute for chemical pesticides. Many species of
actinomycetes, especially the genus Streptomyces, are well known as biocontrol
agents. We investigated the culturable community composition and biological
control ability of endophytic Streptomyces sp. associated with an ethanobotanical
plant Schima wallichi. A total of 22 actinobacterial strains were isolated from
different organs of selected medicinal plants and screened for their biocontrol
ability against seven fungal phytopathogens. Seven isolates showed significant
inhibition activity against most of the selected pathogens. Their identification
based on 16S rRNA gene sequence analysis, strongly indicated that all strains
belonged to the genus Streptomyces. An endophytic strain BPSAC70 isolated from
root tissues showed highest percentage of inhibition (98.3 %) against Fusarium
culmorum with significant activity against other tested fungal pathogens.
Phylogenetic analysis based on 16S rRNA gene sequences revealed that all seven
strains shared 100 % similarity with the genus Streptomyces. In addition, the
isolates were subjected to the amplification of antimicrobial genes encoding
polyketide synthase type I (PKS-I) and nonribosomal peptide synthetase (NRPS) and
found to be present in most of the potent strains. Our results identified some
potential endophytic Streptomyces species having antagonistic activity against
multiple fungal phytopathogens that could be used as an effective biocontrol
agent against pathogenic fungi.
PMID- 29334065
TI - Pexophagy in Penicillin G Secretion by Penicillium chrysogenum PQ-96.
AB - Penicillin G oversecretion by Penicillium chrysogenum PQ-96 is associated with a
strictly adjusted cellular organization of the mature and senescent mycelial
cells. Abundant vacuolar phagy and extended cellular vacuolization combined with
vacuolar budding resulting in the formation of vacuolar vesicles that fuse with
the cell membrane are the most important characteristic features of those cells.
We suggest as follows: if the peroxisomes are integrated into vacuoles, the
penicillin G formed in peroxisomes might be transferred to vacuoles and later
secreted out of the cells by an exocytosis process. The peroxisomal cells of the
mycelium are privileged in penicillin G secretion.
PMID- 29334066
TI - Comparative Study of Microcalorimetric Behavior of Escherichia coli, Proteus
mirabilis and Klebsiella pneumoniae.
AB - To analyze the microcalorimetric behaviour of Escherichia coli, Proteus mirabilis
and Klebsiella pneumoniae, and to test the prospective use of microcalorimetry in
the early diagnosis of infections by enterobacteria. For our experiments we used
cultures of E. coli, P. mirabilis and K. pneumoniae. For the experimental setup,
we used a Calvet microcalorimeter with the constant temperature of 309 K inside.
Using the measured difference of heat power generated by the cells over time, we
obtained growth graphs of the three bacterial species grown at different
densities. The generated curves have characteristic plot that repeats for each
bacterial species at all the concentrations studied. We observed an inversely
proportional relationship between inoculum size and the time until signal
detection; the smaller inoculum, the longer time for the signal detection. In all
conducted experiments, even with low number of bacteria (10 CFU/ml) as inoculum,
we could identify bacterial growth in the sample within 8 hours. Microcalorimetry
could be an efficient technique used for the early detection and identification
of enterobacteria in a culture medium.
PMID- 29334067
TI - In Search of the Antimicrobial Potential of Benzimidazole Derivatives.
AB - A broad series of 4,5,6,7-tetrahalogenated benzimidazoles and 4-(1H-benzimidazol
2-yl)-benzene-1,3-diol derivatives was tested against selected bacteria and
fungi. For this study three plant pathogens Colletotrichum sp., Fusarium sp., and
Sclerotinia sp., as well as Staphylococcus sp., Enterococcus sp., Escherichia
sp., Enterobacter sp., Klebsiella spp. , and Candida spp. as human pathogens were
used. MIC values and/or area of growth reduction method were applied in order to
compare the activity of the synthesized compounds. From the presented set of 22
compounds, only 8, 16, 18 and 19 showed moderate to good inhibition against
bacterial strains. Against Candida strains only compound 19 with three hydroxyl
substituted benzene moiety presented high inhibition at nystatin level or lower.
PMID- 29334068
TI - Microbial Products and Biofertilizers in Improving Growth and Productivity of
Apple - a Review.
AB - The excessive use of mineral fertilizers causes many negative consequences for
the environment as well as potentially dangerous effects of chemical residues in
plant tissues on the health of human and animal consumers. Bio-fertilizers are
formulations of beneficial microorganisms, which upon application can increase
the availability of nutrients by their biological activity and help to improve
soil health. Microbes involved in the formulation of bio-fertilizers not only
mobilize N and P but mediate the process of producing crops and foods naturally.
This method avoids the use of synthetic chemical fertilizers and genetically
modified organisms to influence the growth of crops. In addition to their role in
enhancing the growth of the plants, biofertilizers can act as biocontrol agents
in the rhizosphere at the same time. Biofertilizers are very safe for human,
animal and environment. The use of Azotobacter, Azospirillum, Pseudomonas,
Acetobacter, Burkholderia, Bacillus, Paenibacillus and some members of the
Enterobacteriaceae is gaining worldwide importance and acceptance and appears to
be the trend for the future.
PMID- 29334069
TI - Quantitative Estimation of Porcine Endogenous Retrovirus Release from PK15 Cells.
AB - The present study focuses on the assessment of porcine endogenous retrovirus
(PERV) release from PK15 cells in a time dependent manner. The highest amount of
PERV A RNA was detected in PK15 cells after 16 hours of culture. The highest
amount of PERV B RNA was detected in PK15 cells after 20 hours. The highest
amount of both subtypes RNAs was detected in culture medium after 32 hours of
culture. The peaks of PERV reverse transcriptase (RT) activity were detected
after 28 h of culture in PK15 cells and after 32 hours in the culture medium. The
monitoring of PERV release from PK15 cell line may be useful for the evaluation
of PERV replication.
PMID- 29334070
TI - Ethanol Production Potential of Ethanol-Tolerant Saccharomyces and Non
Saccharomyces Yeasts.
AB - Four ethanologenic ethanol-tolerant yeast strains, Saccharomyces cerevisiae
(ATKU132), Saccharomycodes ludwigii (ATKU47), and Issatchenkia orientalis (ATKU5
60 and ATKU5-70), were isolated by an enrichment technique in yeast extract
peptone dextrose (YPD) medium supplemented with 10% (v/v) ethanol at 30 degrees
C. Among non-Saccharomyces yeasts, Sd. ludwigii ATKU47 exhibited the highest
ethanol-tolerance and ethanol production, which was similar to S. cerevisiae
ATKU132. The maximum range of ethanol concentrations produced at 37 degrees C by
S. cerevisiae ATKU132 and Sd. ludwigii ATKU47 from an initial D-glucose
concentration of 20% (w/v) and 28% (w/v) sugarcane molasses were 9.46-9.82% (w/v)
and 8.07-8.32% (w/v), respectively.
PMID- 29334071
TI - Genetic Variability and Proteome Profiling of a Radiation Induced Cellulase
Mutant Mushroom Pleurotus florida.
AB - We report the genetic similarity changes between a mutant mushroom (Pleurotus
florida, designated as PfCM4) having increased cellulolytic activity developed
through radiation mutagenesis and its wild type by amplified fragment length
polymorphism (AFLP). On average, 23 AFLP fragments were amplified per primer
combination, and a total of 286 polymorphic fragments (78.57% polymorphism) with
maximal fragment length of 1365 base pairs (bp) were obtained. The genetic
similarity between wild type and PfCM4 was found to be 22.30%. In addition,
mycelial and secreted protein profiling by 2D-PAGE showed at least three and five
different protein spots in the range of 25 kD to 100 kD, respectively, in PfCM4.
It seems that the variation in genetic similarity and different expression of
both mycelial and secreted proteins in PfCM4 in comparison to the wild type could
likely be correlated with its increased cellulolytic activity effected by the
irradiation.
PMID- 29334072
TI - Basidiospore and Protoplast Regeneration from Raised Fruiting Bodies of
Pathogenic Ganoderma boninense.
AB - Ganoderma boninense, a phytopathogenic white rot fungus had sought minimal
genetic characterizations despite huge biotechnological potentials. Thus,
efficient collection of fruiting body, basidiospore and protoplast of G.
boninense is described. Matured basidiocarp raised under the glasshouse
conditions yielded a total of 8.3 * 104 basidiospores/ml using the low speed
centrifugation technique. Mycelium aged 3-day-old treated under an incubation
period of 3 h in lysing enzyme from Trichoderma harzianum (10 mg/ml) suspended in
osmotic stabilizer (0.6 M potassium chloride and 20 mM dipotassium phosphate
buffer) yielded the highest number of viable protoplasts (8.9 * 106 single
colonies) among all possible combinations tested (regeneration media, age of
mycelium, osmotic stabilizer, digestive enzyme and incubation period).
PMID- 29334073
TI - Simultaneous Biodegradation of Phenol and n-Hexadecane by Cryogel Immobilized
Biosurfactant Producing Strain Rhodococcus wratislawiensis BN38.
AB - The capability of the biosurfactant-producing strain Rhodococcus wratislawiensis
BN38 to mineralize both aromatic and aliphatic xenobiotics was proved. During
semicontinuous cultivation 11 g/l phenol was completely degraded within 22 cycles
by Rhodococcus free cells. Immobilization in a cryogel matrix was performed for
the first time to enhance the biodegradation at multiple use. A stable
simultaneous hydrocarbon biodegradation was achieved until the total depletion of
20 g/l phenol and 20 g/l n-hexadecane (40 cycles). The alkanotrophic strain R.
wratislawiensis BN38 preferably degraded hexadecane rather than phenol. SEM
revealed well preserved cells entrapped in the heterogeneous super-macroporous
structure of the cryogel which allowed unhindered mass transfer of xenobiotics.
The immobilized strain can be used in real conditions for the treatment of
contaminated industrial waste water.
PMID- 29334074
TI - Effects of Selected Herbicides on Growth and Nitrogen Fixing Activity of
Stenotrophomonas maltophilia (Sb16).
AB - A study was carried out to determine the effects of paraquat, pretilachlor and 2,
4-D on growth and nitrogen fixing activity of Stenotrophomonas maltophilia (Sb16)
and pH of Jensen's N-free medium. The growth of Sb16 and pH of medium were
significantly reduced with full (X) and double (2X) doses of tested herbicides,
but nitrogen fixing activity was decreased by 2X doses. The nitrogenase activity
had the highest value in samples treated with 1/2X of 2, 4-D on fifth incubation
day, but 2X of 2, 4-D had the most adverse effect. An inhibition in the growth
and nitrogenase activity was recovered on the last days of incubation.
PMID- 29334075
TI - Classifying vortex wakes using neural networks.
AB - Unsteady flows contain information about the objects creating them. Aquatic
organisms offer intriguing paradigms for extracting flow information using local
sensory measurements. In contrast, classical methods for flow analysis require
global knowledge of the flow field. Here, we train neural networks to classify
flow patterns using local vorticity measurements. Specifically, we consider
vortex wakes behind an oscillating airfoil and we evaluate the accuracy of the
network in distinguishing between three wake types, 2S, 2P + 2S and 2P + 4S.
The network uncovers the salient features of each wake type.
PMID- 29334077
TI - Magnitude of the current in 2D interlayer tunneling devices.
AB - Using the Bardeen tunneling method with first-principles wave functions,
computations are made of the tunneling current in graphene/hexagonal-boron
nitride/graphene (G/h-BN/G) vertical structures. Detailed comparison with prior
experimental results is made, focusing on the magnitude of the achievable tunnel
current. With inclusion of the effects of translational and rotational
misalignment of the graphene and the h-BN, predicted currents are found to be
about 15* larger than experimental values. A reduction in this discrepancy, to a
factor of 2.5*, is achieved by utilizing a realistic size for the band gap of the
h-BN, hence affecting the exponential decay constant for the tunneling.
PMID- 29334076
TI - Pt decorated MoS2 nanoflakes for ultrasensitive resistive humidity
sensor.
AB - In this work, we report the fabrication of a low power, humidity sensor where
platinum nanoparticles (NPs) decorated few-layered Molybdenum disulphide
(MoS2) nanoflakes have been used as the sensing layer. A mixed solvent
was used to exfoliate the nanoflakes from the bulk powder. Then the
Pt/MoS2 composites were prepared by reducing Pt NPs from
chloroplatinic acid hexahydrate using a novel reduction technique using sulfide
salt. The successful reduction and composite preparation were confirmed using
various material characterization tools like Scanning Electron Microscopy (SEM),
Atomic Force Microscopy (AFM), Transmission Electron Microscopy (TEM), X-Ray
Diffraction (XRD), X-ray Photoelectron Spectroscopy (XPS), Raman spectroscopy and
UV-visible spectroscopy (UV-Vis). The humidity sensors were prepared by drop
coating the Pt-decorated MoS2 on gold interdigitated electrodes and
then exposed to various levels of relative humidity (RH). Composites with
different weight ratios of Pt were tested and the best response was shown by the
Pt/MoS2 (0.25:1) sample with a record high response of ~4000 times at
85% RH. The response and recovery times were ~92 seconds and ~154 seconds
respectively with repeatable behavior. The sensor performance was found to be
stable when tested over a few months. The underlying sensing mechanisms along
with detailed characterization of the various composites have been discussed.
PMID- 29334078
TI - High PRF ultrafast sliding compound doppler imaging: fully qualitative and
quantitative analysis of blood flow.
AB - Ultrafast compound Doppler imaging based on plane-wave excitation (UCDI) can be
used to evaluate cardiovascular diseases using high frame rates. In particular,
it provides a fully quantifiable flow analysis over a large region of interest
with high spatio-temporal resolution. However, the pulse-repetition frequency
(PRF) in the UCDI method is limited for high-velocity flow imaging since it has a
tradeoff between the number of plane-wave angles (N) and acquisition time. In
this paper, we present high PRF ultrafast sliding compound Doppler imaging method
(HUSDI) to improve quantitative flow analysis. With the HUSDI method, full
scanline images (i.e. each tilted plane wave data) in a Doppler frame buffer are
consecutively summed using a sliding window to create high-quality ensemble data
so that there is no reduction in frame rate and flow sensitivity. In addition, by
updating a new compounding set with a certain time difference (i.e. sliding
window step size or L), the HUSDI method allows various Doppler PRFs with the
same acquisition data to enable a fully qualitative, retrospective flow
assessment. To evaluate the performance of the proposed HUSDI method, simulation,
in vitro and in vivo studies were conducted under diverse flow circumstances. In
the simulation and in vitro studies, the HUSDI method showed improved hemodynamic
representations without reducing either temporal resolution or sensitivity
compared to the UCDI method. For the quantitative analysis, the root mean squared
velocity error (RMSVE) was measured using 9 angles (-12 degrees to 12 degrees )
with L of 1-9, and the results were found to be comparable to those of the UCDI
method (L = N = 9), i.e. ?0.24 cm s-1, for all L values. For the in vivo
study, the flow data acquired from a full cardiac cycle of the femoral vessels of
a healthy volunteer were analyzed using a PW spectrogram, and arterial and venous
flows were successfully assessed with high Doppler PRF (e.g. 5 kHz at L = 4).
These results indicate that the proposed HUSDI method can improve flow
visualization and quantification with a higher frame rate, PRF and flow
sensitivity in cardiovascular imaging.
PMID- 29334079
TI - First heating measurements of endovascular stents in magnetic particle imaging.
PMID- 29334080
TI - Effects of microarchitecture and mechanical properties of 3D microporous PLLA
PLGA scaffolds on fibrochondrocyte and L929 fibroblast behavior.
AB - There are several reports studying cell behavior on surfaces in 2D or in
hydrogels in 3D. However, cell behavior in 3D microporous scaffolds has not been
investigated extensively. In this study, poly(L-lactic acid)/poly(lactic acid-co
glycolic acid) (PLLA/PLGA)-based microporous scaffolds were used to study the
effects of scaffold microarchitecture and mechanical properties on the behavior
of two different cell types, human meniscal fibrochondrocytes and L929 mouse
fibroblasts. In general, cell attachment, spreading and proliferation rate were
mainly regulated by the strut (pore wall) stiffness. Increasing strut stiffness
resulted in an increase in L929 fibroblast attachment and a decrease in
fibrochondrocyte attachment. L929 fibroblasts tended to get more round as the
strut stiffness increased, while fibrochondrocytes tended to get more elongated.
Cell migration increased for both cell types with the increasing pore size.
Migrating L929 fibroblasts tended to get more round on the stiff scaffolds, while
fibrochondrocytes tended to get more round on the soft scaffolds. This study
shows that the behavior of cells on 3D microporous scaffolds is mainly regulated
by pore size and strut stiffness, and the response of a cell depends on the
stiffness of both cells and materials. This study could be useful in designing
better scaffolds for tissue engineering applications.
PMID- 29334081
TI - Bio-inspired all-optical artificial neuromast for 2D flow sensing.
AB - We present the design, fabrication and testing of a novel all-optical 2D flow
velocity sensor, inspired by a fish lateral line neuromast. This artificial
neuromast consists of optical fibres inscribed with Bragg gratings supporting a
fluid force recipient sphere. Its dynamic response is modelled based on the
Stokes solution for unsteady flow around a sphere and found to agree with
experimental results. Tuneable mechanical resonance is predicted, allowing a
deconvolution scheme to accurately retrieve fluid flow speed and direction from
sensor readings. The optical artificial neuromast achieves a low frequency
threshold flow sensing of 5 mm s-1 and 5 MUm s-1 at resonance, with a typical
linear dynamic range of 38 dB at 100 Hz sampling. Furthermore, the optical
artificial neuromast is shown to determine flow direction within a few degrees.
PMID- 29334083
TI - Solvated-electron production using cyanocuprates is compatible with the UV
environment on a Hadean-Archaean Earth.
AB - UV-driven photoredox processing of cyanocuprates can generate simple sugars
necessary for prebiotic synthesis. We investigate the wavelength dependence of
this process from 215 to 295 nm and generally observe faster rates at shorter
wavelengths. The most efficient wavelengths are accessible to a range of
potential prebiotic atmospheres, supporting the potential role of cyanocuprate
photochemistry in prebiotic synthesis on the early Earth.
PMID- 29334082
TI - Economic costs due to workers' sick leave at wastewater treatment plants in
Bulgaria.
AB - BACKGROUND: The compensatory mechanisms of social security include expenses for
sick leave. The aim of the study is to determine the economic cost due to sick
leave among workers in wastewater treatment plants (WWTPs), comparing with the
same economic indicators of the National Social Security Institute (NSSI) in
Bulgaria. MATERIAL AND METHODS: The sick leave of 111 workers at 3 WWTPs was
studied in the period 2012-2014 on the grounds of registered absences from work
due to temporary incapacity for work. The economic indicators of the NSSI, the
gross salary at WWTPs, payable social security contributions and compensatory
payments for sick leave have been used for economic cost calculation for
temporary incapacity of the workers. RESULTS: The frequency of cases and the
frequency of lost days due to temporary incapacity were increased in the observed
period at WWTPs and in Bulgaria, and it is significantly higher for the employed
at WWTPs. The percentage share of workers equivalent to 1.66% at WWTPs have not
worked for an entire year as a result of temporary incapacity in 2012, 2.76% - in
2013, and 4.61% - in 2014. The economic burden due to sick leave at WWTPs was
raised from EUR 4913.02 in 2012 to EUR 16 895.80 for 2014 for employers and the
NSSI. CONCLUSIONS: The frequency of cases and the frequency of lost days due to
temporary incapacity were increased in the observed period at WWTPs and in
Bulgaria, and it is significantly higher for the employed at WWTPs. The economic
burden was equally distributed between employers and the NSSI. Med Pr
2018;69(2):129-141.
PMID- 29334085
TI - SpyCatcher-SpyTag mediated in situ labelling of progeny baculovirus with quantum
dots for tracking viral infection in living cells.
AB - A non-invasive labelling strategy is proposed to label baculovirus via genetic
insertion of a SpyTag into the viral glycoprotein, followed by specific
conjugation with the SpyCatcher protein on modified quantum dots (QDs) through an
isopeptide bond. The labelling method is convenient and efficient and shows
little attenuation of viral infectivity. Therefore, it is a biologically
compatible technique for tracking viral infection.
PMID- 29334084
TI - A cyanine-based fluorescent cassette with aggregation-induced emission for
sensitive detection of pH changes in live cells.
AB - An aggregation-induced emission (AIE) cyanine-based fluorescent cassette with a
large pseudo-Stokes shift was designed and prepared to sensitively image pH
changes in live cells via through-bond energy transfer (TBET) from a
tetraphenylethene (TPE) donor to a cyanine acceptor.
PMID- 29334086
TI - N-Doped graphene-supported PdCu nanoalloy as efficient catalyst for reducing
Cr(vi) by formic acid.
AB - Reducing Cr(vi) to Cr(iii) with formic acid is desirable for environmental
protection, but the sluggish kinetics limits its practical application, which
currently motivates the intensive study of efficient catalysts for this redox
reaction. Here bimetallic PdCu nanoalloy (~5 nm in size) supported by N-doped
graphene was synthesized through a one-pot hydrothermal process. The catalytic
activity of PdCu nanoalloy highly depends on the Pd/Cu atomic ratio and N-doped
graphene support. The obtained Pd6Cu4/NG shows superior catalysis towards the
Cr(vi) reduction by formic acid with a high kinetic constant (kn = 23.2 min-1 mg
1) and a low activation energy (Ea = 34.9 kJ mol-1). Active H atoms were found to
be the exact reductant for the Cr(vi) reduction, quite different from the
reported H2-reduction route. The enhanced catalysis originates from the
electronic and geometric modification of active Pd after formation of PdCu alloy.
Electron transfer from Cu to Pd enhances the electron density of Pd atoms, which
favors the adsorption of the bridging formate intermediate and subsequent
generation of active H atoms over PdCu/NG. The catalyst can be recycled five
times without obvious loss of activity. Our work provides an example to explore
the alloying effect on the catalytic behavior of PdCu alloy, which may shed light
on developing other advanced nanoalloys for Cr(vi) reduction.
PMID- 29334087
TI - Achiral non-fluorescent molecule assisted enhancement of circularly polarized
luminescence in naphthalene substituted histidine organogels.
AB - A naphthalene substituted histidine derivative was found to form an organogel
showing circularly polarized luminescence (CPL) and the addition of non
fluorescent achiral benzoic acids could efficiently enhance the CPL via non
covalent interactions.
PMID- 29334088
TI - Chemically accurate adsorption energies for methane and ethane monolayers on the
MgO(001) surface.
AB - A hybrid QM:QM method that combines MP2 as high-level method on cluster models
with density functional theory (PBE+D2) as low-level method on periodic models is
applied to adsorption of methane and ethane on the MgO(001) surface for which
reliable experimental desorption enthalpies are available. Two coverages are
considered, monolayer (every second Mg2+ ion occupied) and one quarter coverage
(one of eight Mg2+ ions occupied). Structure optimizations are performed at the
hybrid MP2:(PBE+D2) level, with the MP2 energies and forces counterpoise
corrected for basis set superposition error and extrapolated to the complete
basis set limit. For the MP2 calculations on the adsorbate monolayer a two-body
expansion of the lateral molecule-molecule interactions is applied. Higher order
correlation effects are evaluated at the hybrid MP2:(PBE+D2) equilibrium
structures as coupled cluster [CCSD(T)] - MP2 differences adopting smaller basis
sets. The final adsorption energies obtained for monolayer coverage are -14.0 +/-
1.0 and -23.3 +/- 0.6 kJ mol-1 for CH4.MgO(001) and C2H6.MgO(001), respectively.
They agree within 1 kJ mol-1 - well within chemical accuracy limits - with
reference energies of -15.0 +/- 0.6 and -24.4 +/- 0.6 kJ mol-1, respectively. The
latter have been derived from measured desorption enthalpy barriers, taking zero
point vibrational energy (ZPVE) and thermal enthalpy contributions into account.
PMID- 29334089
TI - Asymmetric [4+2] annulations to construct norcamphor scaffolds with 2
cyclopentenone via double amine-thiol catalysis.
AB - An efficient double catalytic system, combining chiral amine and 2
mercaptobenzoic acid, is applied for alpha',beta-regioselective [4+2] annulations
of 2-cyclopentenone with a diversity of activated alkenes, constructing
multifunctional chiral bicycle[2,2,1]heptane scaffolds in good to excellent
yields and enantioselectivities. In comparison with the traditional cross
dienamine species between 2-cyclopentenone and chiral amine, the interrupted
enamine intermediate containing a covalently linked thiol catalyst shows
significantly improved reactivity.
PMID- 29334090
TI - Supramolecular photosensitizers rejuvenate photodynamic therapy.
AB - Owing to its spatiotemporal selectivity and noninvasive nature, photodynamic
therapy (PDT) has become a clinically promising approach for the treatment of a
wide range of cancers and other diseases. However, the full potential of PDT has
not been achieved thus far as a consequence of the lack of optimal
photosensitizers (PSs) and/or smart transport/activation strategies. These
problems, which unfortunately lie at the core of the PDT paradigm, include the
oxygen reliance limits, the effect of PDT on hypoxic tumors, limitations of light
penetration, and undesired skin photosensitization induced by "always on" PSs.
Recently, supramolecular approaches, which rely on the use of non-covalent
interactions to construct biomedical active materials, have become suitable
methods for developing innovative PSs. Non-covalent interactions enable
supramolecular PSs to have sensitive and controllable photoactivities, important
elements needed to maximize photodynamic effects and minimize side effects. In
addition, versatile supramolecular PS-assemblies can be designed so that PDT
occurs synergistically with other therapeutic modalities, e.g., photothermal
therapy, leading to a potential improvement of therapeutic effectiveness. In this
review, recent progress made in the development of supramolecular PSs for
rejuvenating PDT will be presented. Importantly, this discussion also provides a
view of future advances that will likely be made in this area and their potential
clinical applications.
PMID- 29334091
TI - Selectivity shift from paraffins to alpha-olefins in low temperature Fischer
Tropsch synthesis in the presence of carboxylic acids.
AB - A shift of selectivity to long chain alpha-olefins has been observed during
Fischer-Tropsch synthesis over Co catalysts in the presence of carboxylic acids.
The total selectivity to alpha-olefins of 39% was obtained in the presence of
acids. The effect has been ascribed to intermediate formation of esters which
hinder secondary olefin hydrogenation.
PMID- 29334092
TI - Synthetic cells produce a quorum sensing chemical signal perceived by Pseudomonas
aeruginosa.
AB - Recent developments in bottom-up synthetic biology (e.g., lipid vesicle
technology integrated with cell-free protein expression systems) allow the
generation of semi-synthetic minimal cells (in short, synthetic cells, SCs)
endowed with some distinctive capacities of natural cells. In particular, such
approaches provide technological tools and conceptual frameworks for the design
and engineering of programmable SCs capable of communicating with natural cells
by exchanging chemical signals. Here we describe the generation of giant vesicle
based SCs which, via gene expression, synthesize in their aqueous lumen an enzyme
that in turn produces a chemical signal. The latter is a small molecule, which is
passively released in the medium and then perceived by the bacterium Pseudomonas
aeruginosa, demonstrating that SCs and bacteria can communicate chemically. The
results pave the way to a novel basic and applied research area where synthetic
cells can communicate with natural cells, for example for exploring minimal
cognition, developing chemical information technologies, and producing smart and
programmable drug-producing/drug-delivery systems.
PMID- 29334093
TI - Three-component difluoroalkylation and
trifluoromethylthiolation/trifluoromethylselenolation of pi-bonds.
AB - This report describes a new method for three-component difluoroalkylation and
trifluoromethylthiolation/trifluoromethylselenolation of pi-bonds via air-stable
SCF3 and SeCF3 reagents as free-radical initiators of ethyl iododifluoroacetate.
beta-Proton elimination can be overcome effectively in this reaction system, and
a broad substrate scope, including alkenes and alkynes, makes this approach
practical and attractive.
PMID- 29334094
TI - Nine-step total synthesis of (-)-strychnofoline.
AB - Strychnofoline is a Strychnos alkaloid that has unique spirooxindole architecture
and possesses important anticancer activity. Here, we have, for the first time,
reported the enantioselective synthesis of strychnofoline proceeding in only nine
steps from commercially available 6-methoxytryptamine. The efficiency of the
synthesis derives from the use of two sequential transformation steps in the
catalytic asymmetric construction of the spiro[pyrrolidine-3,3'-oxindole] motif
in a facile manner. Our route is amenable to the synthesis of other natural and
synthetic analogs of bioactive spirooxindole alkaloids to access their
therapeutic potential.
PMID- 29334095
TI - Gd3+-Doped MoSe2 nanosheets used as a theranostic agent for bimodal imaging and
highly efficient photothermal cancer therapy.
AB - Recently, two dimensional transition metal dichalcogenides (TMDCs) being used as
nanomedicine have aroused great interest because of their unique photothermal
properties. A simple liquid-phase method was used to prepare gadolinium (Gd3+)
doped molybdenum selenide (MoSe2) nanosheets, and then using poly(ethylene
glycol) (PEG) modification on the surface, MoSe2(Gd3+)-PEG nanosheets were
obtained which had high stability in physiological solutions and showed no
obvious toxicity in vivo. It revealed that Gd3+ used as a paramagnetic material
for MoSe2(Gd3+)-PEG provided a strong contrast effect in magnetic resonance
imaging, furthermore, the MoSe2 showed strong absorption in the near infrared
region, and therefore, MoSe2(Gd3+)-PEG could be used as contrast agent for
photoacoustic imaging (PAI). In in vitro experiments, it was found that
MoSe2(Gd3+)-PEG could effectively increase the temperature to help kill cancer
cells under laser irradiation. In vivo experiments showed that there was an
enhanced permeation and retention effect in the tumor after intravenous injection
measured using magnetic resonance/photoacoustic (MR/PA) bimodal imaging. After
photothermal therapy, a significant suppression effect was achieved for tumors in
mice by injection of these nanosheets with laser irradiation. This work
emphasized that the simple doped TMDC nanomaterials when combined with treatment
and imaging functions achieve a cancer therapy, which will provide a good
opportunity for future diagnosis and treatment of cancer.
PMID- 29334096
TI - Microwave-induced covalent functionalization of few-layer graphene with arynes
under solvent-free conditions.
AB - A non-conventional modification of exfoliated few-layer graphene (FLG) with
different arynes under microwave (MW) irradiation and solvent-free conditions is
reported. The described approach allows reaching fast, efficient and mild
covalent functionalization of FLG.
PMID- 29334097
TI - Artificial light-harvesting supramolecular polymeric nanoparticles formed by
pillar[5]arene-based host-guest interaction.
AB - Artificial light-harvesting nanoparticles were prepared from supramolecular
polymers comprised of pillar[5]arene with anthracene-derived donors and acceptors
through host-guest interactions. The resulting water-dispersible nanoparticles
displayed efficient energy transfer and excellent light harvesting ability in
part because the steric bulk of pillar[5]arene suppressed the self-quenching of
the chromophores.
PMID- 29334098
TI - How a tertiary diamine molecule chelates the silicon dimers of the Si(001)
surface: a real-time scanning tunneling microscopy study.
AB - The patterning of silicon surfaces by organic molecules emerges as an original
way to fabricate innovative nanoelectronic devices. In this regard, we have
studied how a diamine, N,N,N',N'-tetramethylethylenediamine (TMEDA, (CH3)2N
[CH2]2-N(CH3)2), chelates the silicon dimers of the Si(001)-2 * 1 surface.
Starting from very low coverage to surface saturation (at 300 K), we used real
time scanning tunneling microscopy (STM) in a scanning-while-dosing approach. The
images show that the molecules can adopt two bonding configurations: the cross
trench (CT) configuration by bridging two adjacent dimer rows, and the end-bridge
(EB) configuration by chelating two adjacent dimers in the same row. However,
while CT dominates over EB at low coverage, the percentage of EB adducts steadily
increases, until it becomes largely dominant at high molecular coverage. Above a
critical coverage thetamol of ~0.13 monolayer (ML), a sudden change in the
molecular imprints is seen, likely due to a change in the tunneling conditions.
The EB stapling of two adjacent dimers in a row via a dual-dative bond (as shown
by XPS) is achieved efficiently by the TMEDA molecule with a very high chemical
selectivity. The EB is a unique configuration in amine adsorption chemistry, as
it leads to the formation of a pair of first-neighbor, doubly-occupied dangling
bonds. Further reactivity of the EB site with other molecules remains to be
explored, and possible reaction schemes are envisaged.
PMID- 29334099
TI - Composition-dependent emission linewidth broadening in lead bromide perovskite
(APbBr3, A = Cs and CH3NH3) nanoparticles.
AB - Lead halide perovskite nanoparticles (NPs) are attractive as they exhibit
excellent color purity and have a tunable band gap, and can thus be applied in
highly efficient photovoltaic and light-emitting diodes. Fundamental studies of
emission linewidth broadening due to spectral shifts in perovskite NPs may
suggest a way to improve their color purity. However, the carrier-induced Stark
shift that causes spectral diffusion still requires investigation. In this study,
we explore composition-related emission linewidth broadening by comparing CsPbBr3
and CH3NH3PbBr3 (MAPbBr3) perovskite NPs. We find that the MAPbBr3 NPs are more
sensitive to fluctuations in the local electric fields than the CsPbBr3 NPs due
to an intrinsic difference in the dipole moment between the two A cations (Cs and
MA), which shows a carrier-induced Stark shift. The results indicate that the
compositions of perovskite NPs are closely associated with emission linewidth
broadening and they also provide insights into the development of NP-based
devices with high color purity.
PMID- 29334100
TI - First-principles simulation of local response in transition metal dichalcogenides
under electron irradiation.
AB - Electron beam irradiation by transmission electron microscopy (TEM) is a common
and effective method for post-synthesis defect engineering in two-dimensional
transition metal dichalcogenides (TMDs). Combining density functional theory
(DFT) with relativistic scattering theory, we simulate the generation of such
defects in monolayer group-VI TMDs, MoS2, WS2, MoSe2, and WSe2, focusing on two
fundamental TEM-induced atomic displacement processes: chalcogen sputtering and
chalcogen vacancy migration. Our calculations show that the activation energies
of chalcogen sputtering depend primarily on the chalcogen species, and are
smaller in selenides than in sulfides. Meanwhile, chalcogen vacancy migration
activation energies hinge on the transition metal species, being smaller in TMDs
containing Mo. Incorporating these energies into a relativistic, temperature
dependent cross section, we predict that, with appropriate TEM energies and
temperatures, one can induce migrations in all four group-VI TMDs without
simultaneously producing vacancies at a significant rate. This can allow for the
formation of complicated defects and extended patterns, and thus, for the
controlled manipulation of TMD crystals for targeted functionality, without the
risk of substantial collateral damage.
PMID- 29334101
TI - Semiconductor-metal structural phase transformation in MoTe2 monolayers by
electronic excitation.
AB - Optical modulation of the crystal structure and materials properties is an
increasingly important technique for functionalization of two-dimensional and
layered semiconductors, where traditional methods like chemical doping are
ineffective. Controllable transformation between the semiconducting (H) and
semimetallic (T') polytypes of transition metal chalcogenide monolayers is of
central importance to two-dimensional electronics, and thermally-driven and
strain-driven examples of this phase transformation have been previously
reported. However, the possibility of a H-T' phase transformation driven by
electronic or optical excitation is less explored and little is known about the
potential energy surface and the magnitude of activation barriers or the
mechanism of the phase transformation in the excited state. Here, we model the
electronic and ionic structure of excited MoTe2 crystals and demonstrate how
electronic excitation leads to a Fermi-surface-nesting driven softening of phonon
modes at the Brillouin zone boundary and the subsequent stabilization of a low
energy intermediate crystal structure along the semiconductor-metal phase
transition pathway. The significantly reduced barriers for this transformation
upon electronic excitation suggest that optical excitation may enable rapid and
controllable synthesis of lateral semiconductor-metal heterophase homojunctions
in monolayer materials for use in next-generation two-dimensional nano
electronics applications.
PMID- 29334102
TI - Ru nanoparticles dispersed on magnetic yolk-shell nanoarchitectures with Fe3O4
core and sulfoacid-containing periodic mesoporous organosilica shell as
bifunctional catalysts for direct conversion of cellulose to isosorbide.
AB - A green and sustainable approach for biorefining involves the development of
bifunctional catalysts for the one-pot conversion of cellulosic biomass to
isosorbide. This requires highly efficient, easily separated and versatile metal
acid catalysts for hydrolysis-hydrogenation-dehydration cascade reactions.
Herein, we report a new type of metal-acid bifunctional catalyst by dispersing Ru
nanoparticles (NPs) on magnetic yolk-shell nanoarchitectures comprising an Fe3O4
core and a sulfoacid (SO3H)-containing periodic mesoporous organosilica shell.
The resultant magnetic Ru-SO3H nanoreactors are highly porous and have large
surface areas (>350 m2 g-1), uniform mesopores (~3.8 nm), well-dispersed Ru NPs
(<1.5 wt%) and superior magnetization. Tailoring the size of the Ru NPs and the
amount of SO3H moieties produced a highly efficient Ru-SO3H nanocatalyst, which
delivered a high yield of isosorbide of 58.1% with almost complete conversion of
cellulose in 2 h and achieved maximum productivity of 2.19 molIsosor h-1 gRu-1,
which was one order of magnitude higher than that achieved using other Ru
containing acidic catalysts. Moreover, the elaborately fabricated Ru-SO3H
nanocatalyst can be easily separated by applying an external magnetic field and
can be cycled four times. This work reveals new possibilities for the fabrication
of highly efficient, easily separated metal-acid catalysts in virtue of the
concept of nanoreactor design.
PMID- 29334103
TI - Unexpected cleavage of upper rim-bridged calix[4]arenes leading to linear
oligophenolic derivatives.
AB - Regioselective meta-mercuration followed by Pd-catalysed intramolecular bridging
gave birth to a novel type of calixarene bearing a single bond bridge between the
meta positions of the neighboring aromatic subunits. These bridged derivatives
possess extremely distorted cavities that imply possible amended properties over
common calix[4]arenes. This new type of calixarene reactivity can be documented
by acid-/electrophile-mediated cleavage of the basic macrocyclic skeleton leading
to open oligomeric structures-the behavior of which has never been observed
before in classic calix[4]arenes bearing alkoxy groups on the lower rim.
PMID- 29334104
TI - One-pot cascade synthesis of azabicycles via the nitro-Mannich reaction and N
alkylation.
AB - A one-pot, metal-free process for the synthesis of azabicycles is developed. The
key transformations involved a cascade of double intramolecular cyclizations via
the nitro-Mannich reaction and N-alkylation, providing various ring systems of
azabicycles in yields up to 81% and an isomeric ratio of 62 : 1. This approach
offers considerable advantages in terms of the handling of small molecules, the
flexibility to introduce a functionalized side chain, and gives direct access to
various azabicycles.
PMID- 29334105
TI - Specific labeling of mitochondria of Chlamydomonas with cationic helicene
fluorophores.
AB - Twelve cationic helicenes and one triangulene were tested for the specific
labeling of mitochondria from algal cells. Octyl ester derivative 5 readily
penetrates algal cells and gives rise to clear fluorescence patterns when it is
used at concentrations in the MUM range. Under these conditions, cell structures
are well preserved and cell survival is not compromised. Cationic helicene
compounds such as 5 provide new useful tools for examining the mitochondrial
network and its dynamics including fission and fusion events.
PMID- 29334106
TI - Large-scale preparation of a 3D patchy surface with dissimilar dendritic
amphiphiles.
AB - We show here the first example of the large-scale surface decoration of a
macroscopic and porous monolith with dissimilar micropatches. Branched
polyethylenimine (PEI) is alkylated with poly(propylene glycol) (PPG), leading to
a reverse-micelle-like dendritic amphiphile of PEI@PPG. Peralkylation and partial
quaternization of the residual amino groups of PEI@PPG produces a cationic
dendritic amphiphile of PEI-N+@PPG. The two dendritic amphiphiles jointly
stabilize a water-in-oil high-internal-phase emulsion to prepare open-cellular
monoliths of macroscopic size, with the monolith pore surface dictated by the
cationic and neutral dendritic amphiphiles. The amino groups of the neutral
amphiphile are further derivatized into anionic dithiocarbamates. The resulting
monolith, along with the dissimilar functional patches on the surface,
simultaneously eliminates multiple anionic and cationic micropollutants from
water to very low residues, and affords the pH-triggered sequential release. Our
strategy of using dissimilar dendritic amphiphiles rather than block copolymers
as surface building blocks can confer the resulting surface with robust and
predesigned microenvironments besides the conventional coacervate structure, and
thus can afford more functions.
PMID- 29334108
TI - Porous layered stacked MnCo2O4 cubes with enhanced electrochemical capacitive
performance.
AB - The development of new electrode materials with various components, structures,
morphologies and porosities is critical for improving the performance of
supercapacitors. Here, we report a facile strategy for synthesizing porous
layered stacked MnCo2O4 cubes through a hydrothermal method, followed by
annealing treatment. Compared with other morphologies of MnCo2O4, the specific
capacitance of porous layered stacked MnCo2O4 cubes reaches 480.5 F g-1 at a
current density of 1 A g-1. Furthermore, porous layered stacked MnCo2O4 cubes
show an ultrahigh capacity retention of 75.7% even at a current density of 25 A g
1 and good cycling stability with 96.6% specific capacitance retained after 3000
cycles, which makes porous layered stacked MnCo2O4 cubes a great potential
electrode material for supercapacitor applications.
PMID- 29334109
TI - A multifunctional supramolecular hydrogel: preparation, properties and molecular
assembly.
AB - A novel supramolecular hydrogel was designed and constructed by molecular self
assembly of a cationic gemini surfactant, 1,3-bis(N,N-dimethyl-N-cetylammonium)-2
propylacrylate dibromide (AGC16), and an anionic aromatic compound, trisodium
1,3,6-naphthalenetrisulfonate (NTS). Owing to its unique structure, the hydrogel
(abbreviated as AGC16/NTS) has the potential to be used as a multifunctional drug
delivery system. The structure and properties of AGC16/NTS were characterized by
rheological measurements, differential scanning calorimetry, variable-temperature
1H nuclear magnetic resonance, ultraviolet-visible spectroscopy, variable
temperature fluorescence emission spectroscopy, cryogenic scanning electron
microscopy, transmission electron microscopy and X-ray diffraction methods. The
rheological and DSC analysis results revealed that the gel AGC16/NTS was formed
below 57 degrees C. It was found from UV-vis, fluorescence and 1H NMR
spectroscopy characterization that aromatic pi-pi stacking and hydrophobic forces
were indispensable to the formation of AGC16/NTS. The Cryo-SEM and TEM
observation results indicated that gelators AGC16 and NTS self-assembled into one
dimensional fibers which further tightly intertwined to form a three-dimensional
network structure. Based on the spectroscopic data and X-ray diffraction
measurement results, a self-assembly model was proposed, helping to further
understand the molecular self-assembly mechanism of AGC16/NTS. It was also found
that the electrostatic force, hydrophobic force and pi-pi interaction were the
three main driving forces for the gelation. The multiple non-covalent
interactions between AGC16 and NTS endowed the hydrogel with excellent
performance when the hydrogel was used as a carrier for drug delivery, due to
multiple micro-domains within the same gel system. We further investigated the
encapsulation and releasing properties of the hydrogel, using the hydrophobic
model drug curcumin (Cur) and the model drug naproxen sodium (Npx) with aromatic
ring structure. The fluorescence spectroscopy analysis confirmed that Npx was
carried through aromatic pi-pi stacking and the 1H NMR measurement result
revealed that Cur was encapsulated within the hydrophobic cavities of AGC16/NTS
through hydrophobic interaction. Moreover, the drug release study results showed
a sustained release of drugs from the hydrogel, indicating good application
prospects in exploring new multifunctional drug delivery systems.
PMID- 29334111
TI - Constructing two-dimensional CuFeSe2@Au heterostructured nanosheets with an
amorphous core and a crystalline shell for enhanced near-infrared light water
oxidation.
AB - Although substantial efforts have been made toward the synthesis of noble metal
semiconductor heteronanostructures, direct in situ synthesis of two-dimensional
(2D) core-shell semiconductor@noble metal heterostructured nanosheets remains
largely unexplored. Herein, we report the synthesis of a novel 2D core-shell
CuFeSe2@Au heterostructured nanosheet with an amorphous core and a crystalline
shell based on the reversed growth of Au nanosheets on the CuFeSe2 frameworks
under near-infrared (NIR) illumination. The nanosheet exhibits strong absorbance
in the NIR region, and the valence band top of CuFeSe2@Au nanosheets is higher
than the oxidation potential of O2/H2O. Owing to the unique structural features,
the resulting nanosheets show excellent photocatalytic activity and high
stability toward water oxidation with an O2 generation rate up to 3.48 mmol h-1 g
1 compared to those of the constituent materials under NIR light irradiation
(lambda > 850 nm). This work brings new opportunities to prepare 2D core-shell
semiconductor@noble metal heterostructured nanosheets, which can be applied as
photocatalysts toward water splitting and solar energy conversion at long
wavelengths.
PMID- 29334114
TI - Sensing local pH and ion concentration at graphene electrode surfaces using in
situ Raman spectroscopy.
AB - We report a novel approach to probe the local ion concentration at graphene/water
interfaces using in situ Raman spectroscopy. Here, the upshifts observed in the G
band Raman mode under applied electrochemical potentials are used to determine
the charge density in the graphene sheet. For voltages up to +/-0.8 V vs. NHE, we
observe substantial upshifts in the G band Raman mode by as much as 19 cm-1,
which corresponds to electron and hole carrier densities of 1.4 * 1013 cm-2 and
Fermi energy shifts of +/-430 meV. The charge density in the graphene electrode
is also measured independently using the capacitance-voltage characteristics
(i.e., Q = CV), and is found to be consistent with those measured by Raman
spectroscopy. From charge neutrality requirements, the ion concentration in
solution per unit area must be equal and opposite to the charge density in the
graphene electrode. Based on these charge densities, we estimate the local ion
concentration as a function of electrochemical potential in both pure DI water
and 1 M KCl solutions, which span a pH range from 3.8 to 10.4 for pure DI water
and net ion concentrations of +/-0.7 mol L-1 for KCl under these applied
voltages.
PMID- 29334115
TI - Label-free multidimensional information acquisition from optogenetically
engineered cells using a graphene transistor.
AB - The optogenetic technique, which allows the manipulation of cellular activity
patterns in space and time by light, has transformed the field of neuroscience.
However, acquiring multidimensional optogenetic information remains challenging
despite the fact that several cellular information detection methods have been
proposed. Herein, we present a new method to acquire label-free multidimensional
information from optogenetically engineered cells using a graphene transistor.
Using a graphene film to form a strong densely packed layer with cells, the
cellular action potentials were characterized as light-activated transistor
conductance signals, which quantified the multidimensional optogenetic
information. Based on this approach, some important cellular optogenetic
information, including electrophysiological state, cell concentration, expression
levels of opsin and response to variable light intensity, were also precisely
detected. Furthermore, the graphene transistor was also used to distinguish cells
expressing different channelrhodopsin-2 variants. Our study offers a general
detection method of multidimensional optogenetic information for extending the
applications of the optogenetic technique and provides a novel sensor for the
development of future biological prosthetic devices.
PMID- 29334116
TI - Interface engineering of a CeO2-Cu3P nanoarray for efficient alkaline hydrogen
evolution.
AB - It is of great importance to design and develop highly active electrocatalysts
for the hydrogen evolution reaction (HER) under alkaline conditions. In this
work, we report the development of a CeO2-Cu3P nanoarray supported on nickel foam
(CeO2-Cu3P/NF) as an excellent HER catalyst with the demand of an overpotential
of only 148 mV to deliver a geometrical catalytic current density of 20 mA cm-2
in 1.0 M KOH. Remarkably, this catalyst also shows strong long-term
electrochemical durability for at least 100 h with nearly 100% Faradaic
efficiency. Density functional theory calculations reveal that the CeO2-Cu3P/NF
hybrid has a lower water dissociation energy and a more thermo-neutral hydrogen
adsorption free energy.
PMID- 29334117
TI - The relationship between office type and job satisfaction: Testing a multiple
mediation model through ease of interaction and well-being.
AB - Objectives This cross-sectional study investigated the associations between
office type (cellular, shared-room, small open-plan, and medium-sized open-plan)
and employees' ease of interaction with coworkers, subjective well-being, and job
satisfaction. Methods A brief survey including measures of office type, ease of
interaction with coworkers, subjective well-being, and job satisfaction was sent
electronically to 1500 Swedish real-estate agents, 271 of whom returned usable
surveys. The data were analyzed using a regression-based serial multiple
mediation model (PROCESS Model 6), which tested whether the relationship between
office type and job satisfaction would be mediated by ease of interaction and, in
turn, subjective well-being. Results A negative relationship was found between
the number of coworkers sharing an office and employees' job satisfaction. This
association was serially mediated by ease of interaction with coworkers and
subjective well-being, with employees working in small and medium-sized open-plan
offices reporting lower levels of both these aspects than employees who work in
either cellular or shared-room offices. Conclusions Open-plan offices may have
short-term financial benefits, but these benefits may be lower than the costs
associated with decreased job satisfaction and well-being. Therefore, decision
makers should consider the impact of office type on employees rather than
focusing solely on cost-effective office layout, flexibility, and productivity.
PMID- 29334118
TI - Markers of proliferation and invasiveness in somatotropinomas.
AB - Introduction In the search for markers of invasiveness of pituitary adenomas, we
studied the expression of Ki-67 antigen, TOPO 2A (topoisomerase 2 alpha), AIP
(Aryl Hydrocarbon Receptor-Interacting Protein) and VEGF (Vascular Endothelial
Growth Factor) in somatotropinomas. Material and Methods We retrospectively
studied a group of 31 patients who underwent pituitary tumour surgery. Expression
of Ki-67, TOPO 2A, AIP and VEGF in surgical specimens was determined by
immunohistochemistry. Relations between quantitatively determined markers and
clinical symptoms, tumour features, and MR imaging, were analysed. Acromegaly was
confirmed by hormonal tests in all patients studied. Local invasiveness
(cavernous sinus penetration, optic chiasm compression or suprasellar extension)
was observed in 18/31 patients (58,1%). Results Ki-67 was expressed in 77.4%,
TOPO 2A in 87.1%, AIP in 83.8%, and VEGF in 87.1% of 31 cases of somatropinoma.
Median values of Ki-67, TOPO 2A, AIP and cytoplasmic VEGF indices were 1.2%
[IQR=2.2], 1.5% [IQR=1.6], 21.26% [IQR=20.1] and 20.4% [IQR=15.4], respectively.
Ki-67, TOPO 2A, AIP and VEGF expression was not correlated with age nor with
patient gender (p > 0.05). Only Ki-67 and TOPO 2A correlated with tumour size
(for Ki-67: r=0.42, p=0.025; for TOPO 2A: r=0.53, p=0.003). Ki-67 and TOPO 2A
levels were significantly higher in invasive compared to noninvasive
somatropinomas (Ki67 mean values: 1.85+/-1.33% vs. 0.95+/-1.07%, p=0.024; TOPO 2A
mean values: 2.19+/-1.63% vs. 1.45+/-1.23%, , p=0.011). Conclusions Ki-67, TOPO
2A, AIP and VEGF were expressed in over 70% of all somatotropinomas. Only Ki-67
and TOPO 2A expression correlated with tumour size and tumour invasiveness.
PMID- 29334119
TI - Evaluation of Four Variants of the Thyroid Imaging Reporting and Data System
(TIRADS) Classification in Patients with Multinodular Goitre - initial study.
AB - Purpose The goal this study was to evaluate the utility of four variants of the
Thyroid Imaging Reporting and Data System (TIRADS) in the differentiation of
focal lesions in individuals with multinodular goiter. Materials and Methods The
study was approved by the Local Bioethical Committee. Each patient gave informed
consent before enrolment. A total of 163 nodules in 124 patients with
multinodular goiter were evaluated by ultrasound. B-mode and PD imaging and
strain elastography were performed. Archived images were evaluated via
retrospective analysis using four different proposed TIRADS classifications
Results Sensitivity and specificity of the Horvath, Park, Kwak, and Russ
classifications were 0.625 and 0.769, 0.813 and 0.864, 0.938 and 0.667, and 0.875
and 0.293, respectively. Positive and negative predictive values were 0.227 and
0.95, 0.394 and 0.977, 0.234 and 0.99, and 0.119 and 0.956, respectively. Receive
operating characteristic analysis suggests that the best differentiation
potential was demonstrated by the Kwak classification with an area under the
curve (AUC) of 0.896, followed by the Park (AUC = 0.872), Horvath (AUC = 0.774),
and Russ (AUC = 0.729) classifications. Conclusion The TIRADS classification
proposed by Kwak can be a useful tool in daily practice for the evaluation of
thyroid cancer in individuals with multinodular goiter, particularly for
selecting cases that require biopsy, which may improve and simplify clinical
decision making. To adopt a definitive, comprehensive variant of the TIRADS
classification with potential for universal, practical application, further
prospective studies that include improvement of the lexicon and evaluation of the
full spectrum of thyroid malignancy are warranted.
PMID- 29334120
TI - Protein Phosphatase 1 dephosphorylates TDP-43 and suppresses its function in tau
exon 10 inclusion.
AB - Transactive response DNA-binding protein of 43 kDa (TDP-43) regulates RNA
processing, including alternative splicing of tau exon 10. Pathological TDP-43 is
hyperphosphorylated. However, how do the protein phosphatase(s) (PP) regulate TDP
43 phosphorylation is unclear. Here, we found that both PP1 and PP2A were
coimmunoprecipitated with TDP-43. Treatment with calyculin A, but not with
okadaic acid, increased TDP-43 phosphorylation at Ser379, Ser403/404, and
Ser409/410 in cultured cells. PP1alpha, PP1beta, and PP1gamma interacted with TDP
43. Overexpression of PP1alpha and PP1gamma, but not PP1beta, suppressed TDP-43
phosphorylation at Ser403/404 and Ser409/410 and TDP-43-induced tau exon 10
inclusion. These findings suggest that PP1alpha and PP1gamma regulate TDP-43
phosphorylation and its function in tau exon 10 inclusion mainly through its
phosphorylation at Ser403/404 and Ser409/410.
PMID- 29334121
TI - The multipotency-to-commitment transition in Caenorhabditis elegans-implications
for reprogramming from cells to organs.
AB - In animal embryos, cells transition from a multipotential state, with the
capacity to adopt multiple fates, into an irreversible, committed state of
differentiation. This multipotency-to-commitment transition (MCT) is evident from
experiments in which cell fate is reprogrammed by transcription factors for cell
type-specific differentiation, as has been observed extensively in Caenorhabditis
elegans. Although factors that direct differentiation into each of the three germ
layer types cannot generally reprogram cells after the MCT in this animal,
transcription factors for endoderm development are able to do so in multiple
differentiated cell types. In one case, these factors can redirect the
development of an entire organ in the process of "transorganogenesis". Natural
transdifferentiation also occurs in a small number of differentiated cells during
normal C. elegans development. We review these reprogramming and
transdifferentiation events, highlighting the cellular and developmental contexts
in which they occur, and discuss common themes underlying direct cell lineage
reprogramming. Although certain aspects may be unique to the model system,
growing evidence suggests that some mechanisms are evolutionarily conserved and
may shed light on cellular plasticity and disease in humans.
PMID- 29334122
TI - Inhibition of HSP90alpha protects cultured neurons from oxygen-glucose
deprivation induced necroptosis by decreasing RIP3 expression.
AB - Heat shock protein 90alpha (HSP90alpha) maintains cell stabilization and
regulates cell death, respectively. Recent studies have shown that HSP90alpha is
involved in receptor interacting protein 3 (RIP3)-mediated necroptosis in HT29
cells. It is known that oxygen and glucose deprivation (OGD) can induce
necroptosis, which is regulated by RIP3 in neurons. However, it is still unclear
whether HSP90alpha participates in the process of OGD-induced necroptosis in
cultured neurons via the regulation of RIP3. Our study found that necroptosis
occurs in primary cultured cortical neurons and PC-12 cells following exposure to
OGD insult. Additionally, the expression of RIP3/p-RIP3, MLKL/p-MLKL, and the
RIP1/RIP3 complex (necrosome) significantly increased following OGD, as measured
through immunofluorescence (IF) staining, Western blotting (WB), and
immunoprecipitation (IP) assay. Additionally, data from computer simulations and
IP assays showed that HSP90alpha interacts with RIP3. In addition, HSP90alpha was
overexpressed following OGD in cultured neurons, as measured through WB and IF
staining. Inhibition of HSP90alpha in cultured neurons, using the specific
inhibitor, geldanamycin (GA), and siRNA/shRNA of HSP90alpha, protected cultured
neurons from necrosis. Our study showed that the inhibitor of HSP90alpha, GA,
rescued cultured neurons not only by decreasing the expression of total
RIP3/MLKL, but also by decreasing the expression of p-RIP3/p-MLKL and the
RIP1/RIP3 necrosome. In this study, we reveal that inhibition of HSP90alpha
protects primary cultured cortical neurons and PC-12 cells from OGD-induced
necroptosis through the modulation of RIP3 expression.
PMID- 29334123
TI - Cancer associated fibroblasts tailored tumor microenvironment of therapy
resistance in gastrointestinal cancers.
AB - Gastrointestinal cancers (GI), are a group of highly aggressive malignancies with
heavy cancer-related mortalities. Even if continued development of therapy
methods, therapy resistance has been a great obstruction for cancer treatment and
thereby inevitably leads to depressed final mortality. Peritumoral cancer
associated fibroblasts (CAFs), a versatile population assisting cancer cells to
build a facilitated tumor microenvironment (TME), has been demonstrated exerting
a promotion influence on cancer proliferation, migration, invasion, metastasis,
and also therapy resistance. In this review, we provide an update progress in
describing how CAFs mediate therapy resistance in GI by various means, meanwhile
highlight the crosstalk between CAFs and cancer cells and present some vital
signaling pathways activated by CAFs in this resistant process. Furthermore, we
discuss the current advances in adopting novel drugs against CAFs and how the
knowledge contributing to improved therapy efficacy in clinical practice. In sum,
CAFs create a therapy-resistant TME in several aspects of GI progression,
although some key problems about distinguishing CAFs subpopulations and
controversial issues on pleiotropic CAFs in medication need to be solved for
subsequent clinical application. Predictably, targeting therapy-resistant CAFs is
a promising adjunctive treatment to benefit GI patients.
PMID- 29334124
TI - Use of antiviral medications in drug reaction with eosinophilia and systemic
symptoms (DRESS): A case of infantile DRESS.
AB - A 3-month-old girl with Sturge-Weber syndrome presented with a morbilliform rash,
eosinophilia, and fulminant liver failure to our tertiary pediatric hospital. She
was diagnosed with drug reaction with eosinophilia and systemic symptoms
complicated by viremia and evidence of viral hepatitis on liver biopsy. We
discuss the role of viral reactivation in drug reaction with eosinophilia and
systemic symptoms and the relevance of antiviral therapy in management.
PMID- 29334125
TI - Determination of isoorientin levels in rat plasma after oral administration of
Vaccinum bracteatum Thunb. methanol extract by high-performance liquid
chromatography-tandem mass spectrometry.
AB - A simple, sensitive and rapid liquid chromatography tandem mass spectrometry
method (LC-MS/MS) was developed and validated for the determination of plasma
isoorientin levels in rats. After simple protein precipitation using methanol,
chromatographic analysis was performed using a Synergi 4MU polar-RP 80A column
(150 * 2.0 mm, 4MUm) under isocratic conditions and a mobile phase consisting of
0.1% formic acid in water and methanol (80:20, v/v) at a flow rate of 0.2 mL/min.
In positive electrospray ionization mode, the protonated precursor and product
ion transitions of isoorientin (m/z 449.0 -> 299.1) and of puerarin (the internal
standard; m/z 417.1 -> 297.1) were acquired by multiple reaction monitoring.
Calibration curves obtained for plasma showed good linearity over the
concentration range 1-1000 ng/mL. The lower limit of quantification was 1 ng/mL.
Intra- and inter-day precisions were within 8.8% relative standard deviation.
Accuracies ranged from 92.1 and 109.7%. The isoorientin stability in rat plasma
under typical handling/storage conditions also found to be acceptable. The
developed method was applied successfully to a pharmacokinetic study of
isoorientin orally administered as the methanol extract of Vaccinium bracteatum
Thunb. or administered as pure isoorientin.
PMID- 29334126
TI - Methylated PACs are more potent than their parent compounds: A study of aryl
hydrocarbon receptor-mediated activity, degradability, and mixture interactions
in the H4IIE-luc assay.
AB - Twenty-six polycyclic aromatic compounds (PACs; including native polycyclic
aromatic hydrocarbons [PAHs], hydroxylated PAHs, alkylated and oxygenated PAHs,
and [alkylated] heterocyclic compounds) were investigated for their aryl
hydrocarbon receptor (AhR)-mediated potencies in the H4IIE-luc bioassay.
Potential degradabilities of PACs were investigated by use of various durations
of exposure (24, 48, or 72 h), and various mixtures of PACs including PAHs,
alkylated and oxygenated PAHs, and heterocyclic compounds were tested for their
joint AhR-mediated potency. Additive behaviors of PACs in mixtures were studied
by comparing observed mixture potencies with mixture potencies predicted by use
of the concentration addition model. Methylated derivatives were more potent than
their parent compounds in the H4IIE-luc assay. A time-dependent decrease in
relative potency was observed for all AhR-active compounds, which may be
indicative of in vitro biotransformation. Monomethylated compounds seemed to be
more rapidly transformed than analogous unsubstituted compounds. In addition, the
results showed that the predictive power of the concentration addition model
increased with the number of compounds, suggesting additivity in multicomponent
mixtures. Due to the greater potency of methylated derivatives and their
ubiquitous occurrence, there is a need for further research on the toxicity and
mixture behavior of these environmentally and toxicologically relevant compounds.
Environ Toxicol Chem 2018;37:1409-1419. (c) 2018 SETAC.
PMID- 29334127
TI - Non-enzymatic cross-linking of collagen type II fibrils is tuned via osmolality
switch.
AB - An important aspect in cartilage ageing is accumulation of advanced glycation end
products (AGEs) after exposure to sugars. Advanced glycation results in cross
links formation between the collagen fibrils in articular cartilage, hampering
their flexibility and making cartilage more brittle. In the current study, we
investigate whether collagen cross-linking after exposure to sugars depends on
the stretching condition of the collagen fibrils. Healthy equine cartilage
specimens were exposed to l-threose sugar and placed in hypo-, iso-, or hyper
osmolal conditions that expanded or shrank the tissue and changed the 3D
conformation of collagen fibrils. We applied micro-indentation tests, contrast
enhanced micro-computed tomography, biochemical measurement of pentosidine cross
links, and cartilage surface color analysis to assess the effects of advanced
glycation cross-linking under these different conditions. Swelling of
extracellular matrix due to hypo-osmolality made cartilage less susceptible to
advanced glycation, namely, the increase in effective Young's modulus was
approximately 80% lower in hypo-osmolality compared to hyper-osmolality and
pentosidine content per collagen was 47% lower. These results indicate that
healthy levels of glycosaminoglycans not only keep cartilage stiffness at
appropriate levels by swelling and pre-stressed collagen fibrils, but also
protect collagen fibrils from adverse effects of advanced glycation. These
findings highlight the fact that collagen fibrils and therefore cartilage can be
protected from further advanced glycation ("ageing") by maintaining the joint
environment at sufficiently low osmolality. Understanding of mechanochemistry of
collagen fibrils provided here might evoke potential ageing prohibiting
strategies against cartilage deterioration. (c) 2018 The Authors. Journal of
Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of
Orthopaedic Research Society. J Orthop Res 36:1929-1936, 2018.
PMID- 29334128
TI - Improved liver R2* mapping by pixel-wise curve fitting with adaptive neighborhood
regularization.
AB - PURPOSE: To improve liver R2* mapping by incorporating adaptive neighborhood
regularization into pixel-wise curve fitting. METHODS: Magnetic resonance imaging
R2* mapping remains challenging because of the serial images with low signal-to
noise ratio. In this study, we proposed to exploit the neighboring pixels as
regularization terms and adaptively determine the regularization parameters
according to the interpixel signal similarity. The proposed algorithm, called the
pixel-wise curve fitting with adaptive neighborhood regularization (PCANR), was
compared with the conventional nonlinear least squares (NLS) and nonlocal means
filter-based NLS algorithms on simulated, phantom, and in vivo data. RESULTS:
Visually, the PCANR algorithm generates R2* maps with significantly reduced noise
and well-preserved tiny structures. Quantitatively, the PCANR algorithm produces
R2* maps with lower root mean square errors at varying R2* values and signal-to
noise-ratio levels compared with the NLS and nonlocal means filter-based NLS
algorithms. For the high R2* values under low signal-to-noise-ratio levels, the
PCANR algorithm outperforms the NLS and nonlocal means filter-based NLS
algorithms in the accuracy and precision, in terms of mean and standard deviation
of R2* measurements in selected region of interests, respectively. CONCLUSIONS:
The PCANR algorithm can reduce the effect of noise on liver R2* mapping, and the
improved measurement precision will benefit the assessment of hepatic iron in
clinical practice. Magn Reson Med 80:792-801, 2018. (c) 2018 International
Society for Magnetic Resonance in Medicine.
PMID- 29334129
TI - A mitochondrial-targeted antioxidant improves myofilament Ca2+ sensitivity during
prolonged low frequency force depression at low PO2.
AB - KEY POINTS: Skeletal muscle contractile activity is associated with an enhanced
reactive oxygen species (ROS) generation. At very low PO2, ROS generation by
mitochondria can be elevated in intact cells. An elevated intracellular oxidant
activity may affect muscle force development and recovery from fatigue. We
treated intact single muscle fibres with a mitochondrial antioxidant and
stimulated the fibres to contract at a low extracellular PO2 that is similar to
the intracellular PO2 that is observed during moderate to intense exercise in
vivo. The mitochondrial antioxidant prevented a sustained decrease in the
myofibrillar Ca2+ sensitivity and improved muscle submaximal force development
after fatigue at low extracellular PO2. ABSTRACT: Skeletal muscle can develop a
prolonged low frequency-stimulation force depression (PLFFD) following fatigue
inducing contractions. Increased levels of reactive oxygen species (ROS) have
been implicated in the development of PLFFD. During exercise the skeletal muscle
intracellular PO2 decreases to relatively low levels, and can be further
decreased when there is an impairment in O2 diffusion or availability, such as in
certain chronic diseases and during exercise at high altitude. Since ROS
generation by mitochondria is elevated at very low PO2 in cells, we tested the
hypothesis that treatment of muscle fibres with a mitochondrial-targeted
antioxidant at a very low, near hypoxic, PO2 can attenuate PLFFD. We treated
intact single fibres from mice with the mitochondrial-specific antioxidant SS31,
and measured force development and intracellular [Ca2+ ] 30 min after fatigue at
an extracellular PO2 of ~5 Torr. After 30 min following the end of the fatiguing
contractions, fibres treated with SS31 showed significantly less impairment in
force development compared to untreated fibres at submaximal frequencies of
stimulation. The cytosolic peak [Ca2+ ] transients (peak [Ca2+ ]c ) were equally
decreased in both groups compared to pre-fatigue values. The combined force and
peak [Ca2+ ]c data demonstrated that myofibrillar Ca2+ sensitivity was diminished
in the untreated fibres 30 min after fatigue compared to pre-fatigue values, but
Ca2+ sensitivity was unaltered in the SS31 treated fibres. These results
demonstrate that at a very low PO2, treatment of skeletal muscle fibres with a
mitochondrial antioxidant prevents a decrease in the myofibrillar Ca2+
sensitivity, which alleviates the fatigue induced PLFFD.
PMID- 29334130
TI - Radiofrequency ablation combined with multiple biliary metal stent placement
using short-type single-balloon endoscope in patients with surgically altered
anatomy.
PMID- 29334131
TI - A bayesian method for accelerated magnetic resonance elastography of the liver.
AB - PURPOSE: Magnetic resonance elastography is a noninvasive tool for quantifying
soft tissue stiffness. Magnetic resonance elastography has been adopted as a
clinical method for staging liver fibrosis. However, the application of liver
magnetic resonance elastography requires multiple lengthy breath-holds. We
propose a new data acquisition and processing method to reduce magnetic resonance
elastography scan time. METHODS: A Bayesian image reconstruction method that uses
transform sparsity and magnitude consistency across different phase offsets to
recover images from highly undersampled data is proposed. The method is validated
using retrospectively down-sampled phantom data and prospectively down-sampled in
vivo data (N = 86). RESULTS: The proposed technique allows accurate
quantification of mean liver stiffness up to an acceleration factor of R = 6,
enabling acquisition of a slice in 4.3 s. Bland-Altman analysis indicates that
the proposed technique (R = 6) has a bias of -0.04 kPa and limits of agreement of
-0.36 to + 0.28 kPa when compared with traditional generalized autocalibrating
partial parallel acquisition reconstruction (R = 1.4). CONCLUSION: By exploiting
transform sparsity and magnitude consistency, accurate quantification of mean
stiffness in the liver can be obtained at an acceleration rate of up to R = 6.
This potentially enables the collection of three to four liver slices, as per
clinical protocol, within a single breath-hold. Magn Reson Med 80:1178-1188,
2018. (c) 2018 International Society for Magnetic Resonance in Medicine.
PMID- 29334132
TI - Oxybutynin 3% gel for the treatment of primary focal hyperhidrosis in adolescents
and young adults.
AB - BACKGROUND/OBJECTIVES: There are no reliably effective, well-tolerated topical
agents for the treatment of hyperhidrosis. We sought to evaluate the efficacy and
tolerability of oxybutynin 3% gel in adolescents and young adults with primary
focal hyperhidrosis. METHODS: Patients with severe axillary hyperhidrosis were
treated with topical oxybutynin 3% gel for 4 weeks. Response to treatment was
assessed by calculating change in Hyperhidrosis Disease Severity Score from
baseline to weeks 1 and 4. Change in health-related quality of life was assessed
using the Children's Dermatology Life Quality Index or the Dermatology Life
Quality Index. Adverse effects were evaluated using patient diaries, investigator
global review, and physical examination. RESULTS: Of 10 patients aged 13-24
enrolled, seven completed the study. Of those who completed the study, four
(57.1%) reported reduction in axillary Hyperhidrosis Disease Severity Score at
week 1 and all seven (100%) at week 4. Six patients (85.7%) reported reduction in
Children's Dermatology Life Quality Index or Dermatology Life Quality Index
score. Anticholinergic adverse effects were infrequent. The majority of treatment
related adverse events were mild to moderate in severity. One patient experienced
a severe adverse event. CONCLUSION: Oxybutynin 3% gel reduced hyperhidrosis
severity and improved health-related quality of life in this small pilot study.
Safety and efficacy should be further evaluated in a large, prospective, placebo
controlled study.
PMID- 29334133
TI - Hierarchical Porous Nanosheets Constructed by Graphene-Coated, Interconnected
TiO2 Nanoparticles for Ultrafast Sodium Storage.
AB - Sodium-ion batteries (SIBs) are considered promising next-generation energy
storage devices. However, a lack of appropriate high-performance anode materials
has prevented further improvements. Here, a hierarchical porous hybrid nanosheet
composed of interconnected uniform TiO2 nanoparticles and nitrogen-doped graphene
layer networks (TiO2 @NFG HPHNSs) that are synthesized using dual-functional C3
N4 nanosheets as both the self-sacrificing template and hybrid carbon source is
reported. These HPHNSs deliver high reversible capacities of 146 mA h g-1 at 5 C
for 8000 cycles, 129 mA h g-1 at 10 C for 20 000 cycles, and 116 mA h g-1 at 20 C
for 10 000 cycles, as well as an ultrahigh rate capability up to 60 C with a
capacity of 101 mA h g-1 . These results demonstrate the longest cyclabilities
and best rate capability ever reported for TiO2 -based anode materials for SIBs.
The unprecedented sodium storage performance of the TiO2 @NFG HPHNSs is due to
their unique composition and hierarchical porous 2D structure.
PMID- 29334134
TI - A comprehensive next-generation sequencing assay for the diagnosis of
epidermolysis bullosa.
AB - BACKGROUND: Historically, diagnosis of epidermolysis bullosa has required skin
biopsies for electron microscopy, direct immunofluorescence to determine which
gene(s) to choose for genetic testing, or both. METHODS: To avoid these invasive
tests, we developed a high-throughput next-generation sequencing (NGS)-based
diagnostic assay called EBSEQ that allows simultaneous detection of mutations in
21 genes with known roles in epidermolysis bullosa pathogenicity. Mutations are
confirmed with traditional Sanger sequencing. RESULTS: We present our EBSEQ assay
and preliminary studies on the first 43 subjects tested. We identified 11 cases
of epidermolysis bullosa simplex, five cases of junctional epidermolysis bullosa,
11 cases of dominant dystrophic epidermolysis bullosa, 15 cases of recessive
dystrophic epidermolysis bullosa, and one case that remains without diagnosis. We
also found an additional 52 variants of uncertain clinical significance in 17 of
the 21 epidermolysis bullosa-associated genes tested. Three of the variants of
uncertain clinical significance were also found in three other patients, for a
total of 49 unique variants of uncertain clinical significance. We found the
clinical sensitivity of the assay to be 75% to 98% and the analytical sensitivity
to be 99% in identifying base substitutions and small deletions and duplications.
Turnaround time was 3 to 6 weeks. CONCLUSIONS: EBSEQ is a sensitive, relatively
rapid, minimally invasive, comprehensive genetic assay for the diagnosis of
epidermolysis bullosa.
PMID- 29334135
TI - Liquid Letters.
AB - Using the interfacial jamming of cellulose nanocrystal (CNC) surfactants, a new
concept, termed all-liquid molding, is introduced to produce all-liquid objects
that retain the shape and details of the mold with high fidelity, yet remain all
liquid and are responsive to external stimuli. This simple process, where the
viscosity of the CNC dispersion can range from that of water to a crosslinked
gel, opens tremendous opportunities for encapsulation, delivery systems, and
unique microfluidic devices. The process described is generally applicable to any
functionalized nanoparticles dispersed in one liquid and polymer ligands having
complementary functionality dissolved in a second immiscible liquid. Such
sculpted liquids retain all the characteristics of the liquids but retain shape
indefinitely, very much like a solid, and provide a new platform for next
generation soft materials.
PMID- 29334136
TI - Bayesian network meta-analysis: Efficacy of air insufflation, CO2 insufflation,
water exchange, and water immersion in colonoscopy.
AB - BACKGROUND AND AIM: Colonoscopy is an excellent screening tool for colorectal
cancer. There are four colonoscopy techniques: air insufflation, CO2
insufflation, water exchange, and water immersion. Some studies reported that the
latter three methods are better than the criterion standard (air insufflation),
whereas some studies did not. In order to evaluate the efficacy of the four
colonoscopy techniques, a network meta-analysis was carried out. METHODS: We
searched randomized controlled trials (RCT) published up to September 2017 from
PubMed, Embase, Cochrane library, and Web of Science. Studies referencing the
comparison between at least two of air insufflation, CO2 insufflation, water
exchange, and water immersion were selected. Primary outcomes included pain score
during insertion, polyp detection rate, and adenoma detection rate, and secondary
outcomes included cecal intubation time and cecal intubation rate. Mean
differences or odds ratios and their corresponding 95% credible intervals were
pooled with Bayesian modeling. RESULTS: Forty RCT with 13 734 patients were
included in this network meta-analysis. Our analysis showed that air insufflation
had the highest pain score (surface under the cumulative ranking curve [SUCRA]:
98.8%) and the lowest detection rate of adenoma (SUCRA: 21.3%) and polyp (SUCRA:
16.8%). Water exchange had the lowest pain score (SUCRA: 1.1%) and highest
detection rate of adenoma (SUCRA: 96.0%) and polyp (SUCRA: 98.9%), although it
led to the longest cecal intubation time (SUCRA: 86.9%). CONCLUSIONS: Air
insufflation might be the most unsatisfactory colonoscopy. Meanwhile, water
exchange might be the most efficient colonoscopy.
PMID- 29334137
TI - Calcium phosphate precipitation in experimental gaps between fluoride-containing
fast-setting calcium silicate cement and dentin.
AB - A novel fast-setting calcium silicate cement containing fluoride (novel-CSC) has
been developed for applications in tooth crowns. The aim of this study was to
assess the ability of the novel-CSC to close the experimental gaps at the dentin
cement interface. The novel-CSC was tested against Vitrebond and GC Fuji II LC.
Experimental gaps of 50 or 300 MUm width were created between the materials and
dentin. Specimens with the 300-MUm-wide gap were immersed in phosphate-buffered
saline and the closed gap area was measured during 96 h. All specimens with 50 or
300 MUm gap width were analyzed by scanning electron microscopy equipped with
energy dispersive X-ray spectroscopy (SEM/EDX) to assess the morphology and
chemical composition of the precipitates after 96 h immersion in phosphate
buffered saline. High-resolution micro-computed tomography (MUCT) was used to
evaluate the integrity and continuity of the precipitiates after 96 h and 180 d.
In all novel-CSC samples, precipitates closed the gap area completely after 96 h.
The SEM/EDX revealed that the globular precipitates closing the gap area were
mainly composed of calcium and phosphorus. After 180 d, MUCT indicated thicker
precipitates compared with initial precipitates only in the novel-CSC group,
whereas no precipitates were observed in resin-modified glass ionomers. Novel-CSC
promoted continuous precipitation of calcium phosphate, including apatite, and
closed the experimental gaps.
PMID- 29334138
TI - Moving knife tip on the thoracic aorta: High-risk submucosal tunneling endoscopic
resection procedure for a puzzling submucosal mass in the esophagus.
PMID- 29334139
TI - Interleaved susceptibility-weighted and FLAIR MRI for imaging lesion-penetrating
veins in multiple sclerosis.
AB - PURPOSE: To simultaneously image brain lesions and veins in multiple sclerosis.
METHODS: An interleaved sequence was developed to simultaneously acquire 3
dimensional T2*-weighted (or susceptibility-weighted (SW)) and fluid-attenuated
inversion recovery (FLAIR) images on a 3T MRI system. The pulse sequence
parameters were calculated to minimize signal perturbation from steady state
while maintaining acceptable image contrast and scan time. Fifteen multiple
sclerosis patients were enrolled in this prospective study and underwent a
standard multiple sclerosis imaging protocol. In addition, SW and FLAIR images
were acquired separately and also in an interleaved manner. The SW and FLAIR
images were combined into one image to visualize lesions and penetrating veins.
The contrast ratios between white matter lesions and penetrating veins were
compared between the interleaved sequence and the individual noninterleaved
acquisitions. RESULTS: Interleaved scanning of the FLAIR and the SW pulse
sequences was achieved, producing aligned images, and with similar image contrast
as in the noninterleaved images. A total of 1076 lesions were identified in all
patients on the combined SW-FLAIR image, of which 968 lesions (90%) had visible
penetrating veins. Lesion-to-vein contrast ratio was 32.7 +/- 17.9 (mean +/-
standard deviation) for the interleaved sequence compared with 28.1 +/- 13.7
using the separate acquisitions (P < 0.001). CONCLUSION: The feasibility of
interleaved acquisition of SW and FLAIR images was demonstrated. This sequence
provides self-registered images and facilitates the visualization of veins in
brain lesions. Magn Reson Med 80:1132-1137, 2018. (c) 2018 International Society
for Magnetic Resonance in Medicine.
PMID- 29334140
TI - Slit Tubes for Semisoft Pneumatic Actuators.
AB - This article describes a new principle for designing soft or 'semisoft' pneumatic
actuators: SLiT (for SLit-in-Tube) actuators. Inflating an elastomeric balloon,
when enclosed by an external shell (a material with higher Young's modulus)
containing slits of different directions and lengths, produces a variety of
motions, including bending, twisting, contraction, and elongation. The requisite
pressure for actuation depends on the length of the slits, and this dependence
allows sequential actuation by controlling the applied pressure. Different
actuators can also be controlled using external "sliders" that act as
reprogrammable "on-off" switches. A pneumatic arm and a walker constructed from
SLiT actuators demonstrate their ease of fabrication and the range of motions
they can achieve.
PMID- 29334141
TI - Characterization of macromolecular baseline of human brain using metabolite
cycled semi-LASER at 9.4T.
AB - PURPOSE: Macromolecular resonances (MM) arise mainly from cytosolic proteins and
overlap with metabolites, influencing metabolite quantification. Macromolecules
can serve as valuable biomarkers for diseases and pathologies. The objectives of
this study were to characterize MM at 9.4T in the human brain (occipital and left
parietal lobe) and to describe the RF coil setup used for MM acquisition in the
two regions. METHODS: An adiabatic inversion pulse was optimised for metabolite
nulling at 9.4T using double inversion recovery and was combined for the first
time with metabolite cycled (MC) semi-LASER and appropriate coil configuration.
MM spectra (seven volunteers) from two brain locations were averaged and smoothed
creating MM templates, which were then parametrized using simulated Voigt-shaped
lines within LCModel. Quantification was performed on individual data sets,
including corrections for different tissue composition and the T1 and T2
relaxation of water. RESULTS: Our coil configuration method resulted in efficient
B1+ (>30 T/?kW) for both brain regions. The 15 MM components were detected and
quantified in MM baselines of the two brain areas. No significant differences in
concentration levels of MM between different regions were found. Two new MM peaks
were reported (M7 & M8). CONCLUSION: Double inversion, which was combined with MC
semi-LASER, enabled the acquisition of high spectral resolution MM spectra for
both brain regions at 9.4T. The 15 MM components were detected and quantified.
Two new MM peaks were reported for the first time (M7 & M8) and preliminarily
assigned to beta-methylene protons of aspartyl-groups. Magn Reson Med 80:462-473,
2018. (c) 2018 International Society for Magnetic Resonance in Medicine.
PMID- 29334142
TI - Severe ectropion in lamellar ichthyosis managed medically with oral acitretin.
AB - Congenital ectropion is commonly associated with lamellar ichthyosis. Severe
eyelid ectropion may cause corneal exposure, keratopathy, and permanent corneal
scarring. We report a neonate with severe, bilateral, congenital ectropion and
eclabium managed using oral retinoids. Both corneas were protected with topical
antibiotics and lubricating eyedrops and eye ointments. At 12-month follow-up,
the child was doing well, with no ectropion or corneal opacity.
PMID- 29334143
TI - Childhood alopecia areata-Data from the National Alopecia Areata Registry.
AB - BACKGROUND/OBJECTIVES: Alopecia areata may occur at any age and is the third-most
common dermatosis in children. The objective of this study was to investigate the
clinical and epidemiologic features of children and adolescents with alopecia
areata based on the data of the National Alopecia Areata registry on children and
adolescents. METHODS: Two thousand two hundred eighteen children and adolescents
with alopecia areata self-enrolled in the National Alopecia Areata Registry and
completed a web-based, self-administered, short-intake screening questionnaire
(first tier). In the second tier, 643 patients participated in a clinical
examination and completed a long-form questionnaire. RESULTS: Mean age of onset
was 5.9 +/- 4.1 years. With a female to male ratio of 1.5:1, alopecia areata was
more prevalent in girls, but boys were significantly more likely to have a severe
type (P = .009). One-fourth of all children had a positive family history, with
8% having more than three affected relatives. The disease most commonly
associated with alopecia areata was atopic dermatitis (32.7%). CONCLUSION:
Childhood alopecia areata is more prevalent in girls than in boys, but boys have
more extensive alopecia areata. Despite the low prevalence, congenital alopecia
areata is an important differential diagnosis for neonatal hair loss. Alopecia
areata runs in families, suggesting an underlying genetic background. One-quarter
of the children reported at least one affected first-degree relative; 8% had more
than three affected relatives.
PMID- 29334144
TI - Acute gastrointestinal bleeding from appendiceal diverticulitis diagnosed
preoperatively by combined short-interval computed tomography and colonoscopy: A
case report.
PMID- 29334145
TI - Colloidal Cobalt Phosphide Nanocrystals as Trifunctional Electrocatalysts for
Overall Water Splitting Powered by a Zinc-Air Battery.
AB - Highly efficient and stable electrocatalysts, particularly those that are capable
of multifunctionality in the same electrolyte, are in high demand for the
hydrogen evolution reaction (HER), oxygen evolution reaction (OER), and oxygen
reduction reaction (ORR). In this work, highly monodisperse CoP and Co2 P
nanocrystals (NCs) are synthesized using a robust solution-phase method. The
highly exposed (211) crystal plane and abundant surface phosphide atoms make the
CoP NCs efficient catalysts toward ORR and HER, while metal-rich Co2 P NCs show
higher OER performance owing to easier formation of plentiful Co2 P@COOH
heterojunctions. Density functional theory calculation results indicate that the
desorption of OH* from cobalt sites is the rate-limiting step for both CoP and
Co2 P in ORR and that the high content of phosphide can lower the reaction
barrier. A water electrolyzer constructed with a CoP NC cathode and a Co2 P NC
anode can achieve a current density of 10 mA cm-2 at 1.56 V, comparable even to
the noble metal-based Pt/C and RuO2 /C pair. Furthermore, the CoP NCs are
employed as an air cathode in a primary zinc-air battery, exhibiting a high power
density of 62 mW cm-2 and good stability.
PMID- 29334146
TI - Self-Assembled Ag-MXA Superclusters with Structure-Dependent Mechanical
Properties.
AB - The low elastic modulus and time-consuming formation process represent the major
challenges that impede the penetration of nanoparticle superstructures into daily
life applications. As observed in the molecular or atomic crystals, more
effective interactions between adjacent nanoparticles would introduce beneficial
features to assemblies enabling optimized mechanical properties. Here, a
straightforward synthetic strategy is showed that allows fast and scalable
fabrication of 2D Ag-mercaptoalkyl acid superclusters of either hexagonal or
lamellar topology. Remarkably, these ordered superstructures exhibit a structure
dependent elastic modulus which is subject to the tether length of straight-chain
mercaptoalkyl acids or the ratio between silver and tether molecules. These
superclusters are plastic and moldable against arbitrarily shaped masters of
macroscopic dimensions, thereby opening a wealth of possibilities to develop more
nanocrystals with practically useful nanoscopic properties.
PMID- 29334147
TI - Uniform Lithium Nucleation/Growth Induced by Lightweight Nitrogen-Doped Graphitic
Carbon Foams for High-Performance Lithium Metal Anodes.
AB - The lithium metal anode has attracted soaring attention as an ideal battery
anode. Unfortunately, nonuniform Li nucleation results in uncontrollable growth
of dendritic Li, which incurs serious safety issues and poor electrochemical
performance, hindering its practical applications. Herein, this study shows that
uniform Li nucleation/growth can be induced by an ultralight 3D current collector
consisting of in situ nitrogen-doped graphitic carbon foams (NGCFs) to realize
suppressing dendritic Li growth at the nucleating stage. The N-containing
functional groups guide homogenous growth of Li nucleus nanoparticles and the
initial Li nucleus seed layer regulates the following well-distributed Li growth.
Benefiting from such favorable Li growth behavior, superior electrochemical
performance can be achieved as evidenced by the high Coulombic efficiency (~99.6%
for 300 cycles), large capacity (10 mA h cm-2 , 3140 mA h g-1NGCF-Li ), and
ultralong lifespan (>1200 h) together with low overpotential (<25 mV at 3 mA cm-2
); even under a high current density up to 10 mA cm-2 , it still displays low
overpotential of 62 mV.
PMID- 29334149
TI - Evidence based practice readiness: A concept analysis.
AB - AIM: To analyse and define the concept "evidence based practice readiness" in
nurses. BACKGROUND: Evidence based practice readiness is a term commonly used in
health literature, but without a clear understanding of what readiness means.
Concept analysis is needed to define the meaning of evidence based practice
readiness. METHOD: A concept analysis was conducted using Walker and Avant's
method to clarify the defining attributes of evidence based practice readiness as
well as antecedents and consequences. A Boolean search of PubMed and Cumulative
Index for Nursing and Allied Health Literature was conducted and limited to those
published after the year 2000. Eleven articles met the inclusion criteria for
this analysis. RESULTS: Evidence based practice readiness incorporates personal
and organisational readiness. Antecedents include the ability to recognize the
need for evidence based practice, ability to access and interpret evidence based
practice, and a supportive environment. CONCLUSION: The concept analysis
demonstrates the complexity of the concept and its implications for nursing
practice. The four pillars of evidence based practice readiness: nursing,
training, equipping and leadership support are necessary to achieve evidence
based practice readiness. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers are
in the position to address all elements of evidence based practice readiness.
Creating an environment that fosters evidence based practice can improve patient
outcomes, decreased health care cost, increase nurses' job satisfaction and
decrease nursing turnover.
PMID- 29334148
TI - Self-Powered Si/CdS Flexible Photodetector with Broadband Response from 325 to
1550 nm Based on Pyro-phototronic Effect: An Approach for Photosensing below
Bandgap Energy.
AB - Cadmium sulfide (CdS) has received widespread attention as the building block of
optoelectronic devices due to its extraordinary optoelectronic properties, low
work function, and excellent thermal and chemical stability. Here, a self-powered
flexible photodetector (PD) based on p-Si/n-CdS nanowires heterostructure is
fabricated. By introducing the pyro-phototronic effect derived from wurtzite
structured CdS, the self-powered PD shows a broadband response range, even beyond
the bandgap limitation, from UV (325 nm) to near infrared (1550 nm) under zero
bias with fast response speed. The light-induced pyroelectric potential is
utilized to modulate the optoelectronic processes and thus improve the
photoresponse performance. Lasers with different wavelengths have different
effects on the self-powered PDs and corresponding working mechanisms are
carefully investigated. Upon 325 nm laser illumination, the rise time and fall
time of the self-powered PD are 245 and 277 us, respectively, which are faster
than those of most previously reported CdS-based nanostructure PDs. Meanwhile,
the photoresponsivity R and specific detectivity D* regarding to the relative
peak-to-peak current are both enhanced by 67.8 times, compared with those only
based on the photovoltaic effect-induced photocurrent. The self-powered flexible
PD with fast speed, stable, and broadband response is expected to have extensive
applications in various environments.
PMID- 29334150
TI - A General Method for the Chemical Synthesis of Large-Scale, Seamless Transition
Metal Dichalcogenide Electronics.
AB - The capability to directly build atomically thin transition metal dichalcogenide
(TMD) devices by chemical synthesis offers important opportunities to achieve
large-scale electronics and optoelectronics with seamless interfaces. Here, a
general approach for the chemical synthesis of a variety of TMD (e.g., MoS2 , WS2
, and MoSe2 ) device arrays over large areas is reported. During chemical vapor
deposition, semiconducting TMD channels and metallic TMD/carbon nanotube (CNT)
hybrid electrodes are simultaneously formed on CNT-patterned substrate, and then
coalesce into seamless devices. Chemically synthesized TMD devices exhibit
attractive electrical and mechanical properties. It is demonstrated that
chemically synthesized MoS2 -MoS2 /CNT devices have Ohmic contacts between MoS2
/CNT hybrid electrodes and MoS2 channels. In addition, MoS2 -MoS2 /CNT devices
show greatly enhanced mechanical stability and photoresponsivity compared with
conventional gold-contacted devices, which makes them suitable for flexible
optoelectronics. Accordingly, a highly flexible pixel array based on chemically
synthesized MoS2 -MoS2 /CNT photodetectors is applied for image sensing.
PMID- 29334151
TI - Fused Tris(thienothiophene)-Based Electron Acceptor with Strong Near-Infrared
Absorption for High-Performance As-Cast Solar Cells.
AB - A fused tris(thienothiophene) (3TT) building block is designed and synthesized
with strong electron-donating and molecular packing properties, where three
thienothiophene units are condensed with two cyclopentadienyl rings. Based on
3TT, a fused octacylic electron acceptor (FOIC) is designed and synthesized,
using strong electron-withdrawing 2-(5/6-fluoro-3-oxo-2,3-dihydro-1H-inden-1
ylidene)-malononitrile as end groups. FOIC exhibits absorption in 600-950 nm
region peaked at 836 nm with extinction coefficient of up to 2 * 105 m-1 cm-1 ,
low bandgap of 1.32 eV, and high electron mobility of 1.2 * 10-3 cm2 V-1 s-1 .
Compared with its counterpart ITIC3 based on indacenothienothiophene core, FOIC
exhibits significantly upshifted highest occupied molecular orbital level,
slightly downshifted lowest unoccupied molecular orbital level, significantly
redshifted absorption, and higher mobility. The as-cast organic solar cells
(OSCs) based on blends of PTB7-Th donor and FOIC acceptor without additional
treatments exhibit power conversion efficiencies (PCEs) as high as 12.0%, which
is much higher than that of PTB7-Th: ITIC3 (8.09%). The as-cast semitransparent
OSCs based on the same blends show PCEs of up to 10.3% with an average visible
transmittance of 37.4%.
PMID- 29334152
TI - Dynamic Coordination of Eu-Iminodiacetate to Control Fluorochromic Response of
Polymer Hydrogels to Multistimuli.
AB - New fluorochromic materials that reversibly change their emission properties in
response to their environment are of interest for the development of sensors and
light-emitting materials. A new design of Eu-containing polymer hydrogels showing
fast self-healing and tunable fluorochromic properties in response to five
different stimuli, including pH, temperature, metal ions, sonication, and force,
is reported. The polymer hydrogels are fabricated using Eu-iminodiacetate (IDA)
coordination in a hydrophilic poly(N,N-dimethylacrylamide) matrix. Dynamic metal
ligand coordination allows reversible formation and disruption of hydrogel
networks under various stimuli which makes hydrogels self-healable and
injectable. Such hydrogels show interesting switchable ON/OFF luminescence along
with the sol-gel transition through the reversible formation and dissociation of
Eu-IDA complexes upon various stimuli. It is demonstrated that Eu-containing
hydrogels display fast and reversible mechanochromic response as well in
hydrogels having interpenetrating polymer network. Those multistimuli responsive
fluorochromic hydrogels illustrate a new pathway to make smart optical materials,
particularly for biological sensors where multistimuli response is required.
PMID- 29334153
TI - Heterobimetallic Complexes for Theranostic Applications.
AB - The design of more efficient anticancer drugs requires a deeper understanding of
their biodistribution and mechanism of action. Cell imaging agents could help to
gain insight into biological processes and, consequently, the best strategy for
attaining suitable scaffolds in which both biological and imaging properties are
maximized. A new concept arises in this field that is the combination of two
metal fragments as collaborative partners to provide the precise emissive
properties to visualize the cell as well as the optimum cytotoxic activity to
build more potent and selective chemotherapeutic agents.
PMID- 29334154
TI - Nano Titanium Monoxide Crystals and Unusual Superconductivity at 11 K.
AB - Nano TiO2 is investigated intensely due to extraordinary photoelectric
performances in photocatalysis, new-type solar cells, etc., but only very few
synthesis and physical properties have been reported on nanostructured TiO or
other low valent titanium-containing oxides. Here, a core-shell nanoparticle made
of TiO core covered with a ~5 nm shell of amorphous TiO1+x is newly constructed
via a controllable reduction method to synthesize nano TiO core and subsequent
soft oxidation to form the shell (TiO1+x ). The physical properties measurements
of electrical transport and magnetism indicate these TiO@TiO1+x nanocrystals are
a type-II superconductor of a recorded Tconset = 11 K in the binary Ti-O system.
This unusual superconductivity could be attributed to the interfacial effect due
to the nearly linear gradient of O/Ti ratio across the outer amorphous layer.
This novel synthetic method and enhanced superconductivity could open up
possibilities in interface superconductivity of nanostructured composites with
well-controlled interfaces.
PMID- 29334155
TI - Response selection codes in neurophysiological data predict conjoint effects of
controlled and automatic processes during response inhibition.
AB - The inhibition of prepotent responses is a requirement for goal-directed behavior
and several factors determine corresponding successful response inhibition
processes. One factor relates to the degree of automaticity of pre-potent
response tendencies and another factor relates to the degree of cognitive control
that is exerted during response inhibition. However, both factors can conjointly
modulate inhibitory control. Cognitive theoretical concepts suggest that codings
of stimulus-response translations may underlie such conjoint effects. Yet, it is
unclear in how far such specific codes, as assumed in cognitive psychological
concepts, are evident in neurophysiological processes and whether there are
specific functional neuroanatomical structures associated with the processing of
such codes. Applying a temporal decomposition method of EEG data in combination
with source localization methods we show that there are different, intermingled
codes (i.e., "stimulus codes" and "response selection codes") at the
neurophysiological level during conjoint effects of "automatic" and "controlled"
processes in response inhibition. Importantly, only "response selection codes"
predict behavioral performance, and are subject to conjoint modulations by
"automatic" and "controlled" processes. These modulations are associated with
inferior and superior parietal areas (BA40/BA7), possibly reflecting an updating
of internal representations when information is complex and probably difficult to
categorize, but essential for behavioral control. Codes proposed by cognitive,
psychological concepts seem to have a neurophysiological analogue that fits into
current views on functions of inferior and superior parietal regions.
PMID- 29334156
TI - The retinal ganglion cell layer predicts normal-appearing white matter tract
integrity in multiple sclerosis: A combined diffusion tensor imaging and optical
coherence tomography approach.
AB - We investigated the relationship between retinal layers and normal-appearing
white matter (WM) integrity in the brain of patients with relapsing-remitting
multiple sclerosis (MS), using a combined diffusion tensor imaging and high
resolution optical coherence tomography approach. Fifty patients and 62 controls
were recruited. The patients were divided into two groups according to presence
(n = 18) or absence (n = 32) of optic neuritis. Diffusion tensor data were
analyzed with a voxel-wise whole brain analysis of diffusion metrics in WM with
tract-based spatial statistics. Thickness measurements were obtained for each
individual retinal layer. Partial correlation and multivariate regression
analyses were performed, assessing the association between individual retinal
layers and diffusion metrics across all groups. Region-based analysis was
performed, by focusing on tracts associated with the visual system. Receiver
operating characteristic (ROC) curves were computed to compare the biomarker
potential for the diagnosis of MS, using the thickness of each retinal layer and
diffusion metrics. In patients without optic neuritis, both ganglion cell layer
(GCL) and inner plexiform layer thickness correlated with the diffusion metrics
within and outside the visual system. GCL thickness was a significant predictor
of diffusion metrics in the whole WM skeleton, unlike other layers. No
association was observed for either controls or patients with a history of optic
neuritis. ROC analysis showed that the biomarker potential for the diagnosis of
MS based on the GCL was high when compared to other layers. We conclude that GCL
integrity is a predictor of whole-brain WM disruption in MS patients without
optic neuritis.
PMID- 29334157
TI - Elevated sympathetic vasomotor outflow in response to increased inspiratory
muscle activity during exercise is less in young women compared with men.
AB - NEW FINDINGS: What is the central question of this study? Premenopausal women
have an attenuated inspiratory muscle metaboreflex-induced increase in arterial
blood pressure compared with men. It is unclear whether sympathetic vasomotor
outflow during dynamic exercise with increased inspiratory muscle activation is
less in young women than in men. What is the main finding and its importance? The
magnitude of increased sympathetic vasomotor outflow during leg cycling with
inspiratory resistance was smaller in women than in men. Less sympathetic
vasomotor outflow with inspiratory muscle metaboreflex activation could be one of
the mechanisms for the attenuated inspiratory muscle-induced metaboreflex during
exercise in young women. ABSTRACT: We compared changes in muscle sympathetic
nerve activity (MSNA) and cardiovascular variables during leg cycle exercise with
increased inspiratory muscle resistance in men and women. We hypothesized that
sympathetic vasomotor outflow during exercise with increased inspiratory
resistance would be attenuated in young women compared with age-matched men.
Eight women and seven men completed the study. The subjects performed two 10 min
exercise bouts at 40% peak oxygen uptake using a cycle ergometer in a
semirecumbent position [spontaneous breathing for 5 min and voluntary
hyperventilation with or without inspiratory resistive breathing for 5 min
(breathing frequency 50 breaths min-1 with a 50% duty cycle; inspiratory
resistance 30% of maximal inspiratory pressure)]. Mean arterial blood pressure
(MAP) was acquired using finger photoplethysmography. The MSNA was recorded via
microneurography of the right median nerve at the cubital fossa. During leg cycle
exercise with inspiratory resistive breathing, MSNA burst frequency was
increased, accompanied by an increase in MAP in both men and women. Women,
compared with men, had less of an increase in MAP (women +22.8 +/- 12.3 mmHg
versus men +32.2 +/- 5.4 mmHg; P < 0.05) and MSNA burst frequency (women +9.6 +/-
2.9 bursts min-1 versus men +14.6 +/- 6.4 bursts min-1 ; P < 0.05). These results
suggest that the attenuated inspiratory muscle-induced metaboreflex during
exercise in young women is attributable, in part, to a lesser sympathetic
vasomotor outflow compared with men.
PMID- 29334158
TI - Growth of liver allografts over time in pediatric transplant recipients.
AB - The liver's capacity to grow in response to metabolic need is well known.
However, long-term growth of liver allografts in pediatric recipients has not
been characterized. A retrospective review of pediatric recipients at a single
institution identified patients who had cross-sectional imaging at 1, 5, and 10
years post-transplant. Using volumetric calculations, liver allograft size was
calculated and percent SLV were compared across the different time points; 18
patients ranging from 0.3 to 17.7 years old were identified that had imaging at 2
or more time points. Measured liver volumes increased by 59% after 5 years and
170% after 10 years. The measured liver volumes compared to calculated %SLV for
these patients were 123 +/- 37%, 97 +/- 19%, and 118 +/- 27% at 1, 5, and 10
years after transplant, respectively. Our data suggest that liver allografts in
pediatric recipients increase along with overall growth, and reach SLVs for
height and weight by 5 years post-transplantation. Additionally, as pediatric
recipients grow, the livers appear to maintain appropriate SLV.
PMID- 29334159
TI - A Gold(III) Pincer Ligand Scaffold for the Synthesis of Binuclear and
Bioconjugated Complexes: Synthesis and Anticancer Potential.
AB - Cyclometalated (C^N^C)AuIII complexes bearing functionalized N-heterocyclic
carbene (NHC) ligands provide a high-yielding, modular route to bioconjugated and
binuclear complexes. This methodology has been applied to the synthesis of
bioconjugated complexes presenting biotin and 17alpha-ethynylestradiol vectors,
as well as to the synthesis of bimetallic AuIII /AuI complexes. The in vitro
antiproliferative activities of these compounds against various cancer cells
lines depend on the linker length, with the longer linker being the most potent.
The estradiol conjugate AuC6 Estra proved to be more toxic against the estrogen
receptor positive (ER+) cancer cells than against the ER- cancer cells and non
cancer cells. The bimetallic complex AuC6 Au was more selective for breast cancer
cells with respect to a healthy cell standard than the monometallic complex
AuNHC. The metal uptake study on cells expressing or not biotin and estrogen
receptors revealed an improved and targeted delivery of gold for both the
bioconjugated complexes AuC6 Biot and AuC6 Estra compared to the non-vectorised
analogue AuNHC. The investigations of the interaction of the bioconjugates and
bimetallic complexes with human telomeric G-quadruplex DNA using FRET-melting
techniques revealed a reduced ability to stabilize this DNA structure with
respect to the non-vectorised analogue AuNHC.
PMID- 29334160
TI - Fine-Tuning of Molecular Packing and Energy Level through Methyl Substitution
Enabling Excellent Small Molecule Acceptors for Nonfullerene Polymer Solar Cells
with Efficiency up to 12.54.
AB - A novel small molecule acceptor MeIC with a methylated end-capping group is
developed. Compared to unmethylated counterparts (ITCPTC), MeIC exhibits a higher
lowest unoccupied molecular orbital (LUMO) level value, tighter molecular
packing, better crystallites quality, and stronger absorption in the range of 520
740 nm. The MeIC-based polymer solar cells (PSCs) with J71 as donor, achieve high
power conversion efficiency (PCE), up to 12.54% with a short-circuit current (JSC
) of 18.41 mA cm-2 , significantly higher than that of the device based on
J71:ITCPTC (11.63% with a JSC of 17.52 mA cm-2 ). The higher JSC of the PSC based
on J71:MeIC can be attributed to more balanced MUh /MUe , higher charge
dissociation and charge collection efficiency, better molecular packing, and more
proper phase separation features as indicated by grazing incident X-ray
diffraction and resonant soft X-ray scattering results. It is worth mentioning
that the as-cast PSCs based on MeIC also yield a high PCE of 11.26%, which is
among the highest value for the as-cast nonfullerene PSCs so far. Such a small
modification that leads to so significant an improvement of the photovoltaic
performance is a quite exciting finding, shining a light on the molecular design
of the nonfullerene acceptors.
PMID- 29334161
TI - The Role of Neurosonology in the Diagnosis and Management of Patients with
Carotid Artery Disease: A Review.
AB - Carotid artery disease (CAD) is a common cause of ischemic stroke with high rates
of recurrence. Carotid endarterectomy (CEA) or carotid artery stenting (CAS) are
highly recommended for the secondary prevention of symptomatic CAD during the
first 14 days following the index event of transient ischemic attack or minor
stroke. CEA or CAS may also be offered in selected cases with severe asymptomatic
stenosis. Herein, we review the utility of neurosonology in the diagnosis and pre
/peri-interventional assessment of CAD patients who undergo carotid
revascularization procedures. Carotid ultrasound may provide invaluable
information on plaque echogenicity, ulceration, risk of thrombosis, and rupture.
Transcranial Doppler or transcranial color-coded sonography may further assist by
mapping collateral circulation, evaluating the impairment of vasomotor
reactivity, detecting microembolization, or reperfusion hemorrhage in real time.
Neurosonology examinations are indispensable bedside tools assisting in the
diagnosis, risk stratification, peri-interventional monitoring, and follow-up of
patients with CAD.
PMID- 29334162
TI - Prevalence of metabolic syndrome in children with moderate to severe psoriasis
treated with TNF inhibitors in comparison to conventional agents.
AB - Association of childhood psoriasis with metabolic syndrome has not been studied
well. TNF-alfa contributes to the inflammation seen in metabolic syndrome, and
recently etanercept has shown to reduce the levels of inflammatory markers.
Assessment of prevalence of metabolic syndrome in juvenile psoriasis patients in
Kuwait. We included 236 patients with moderate to severe psoriasis below 18 years
treated for at least 24 weeks with TNF inhibitors (Group A), and equal number of
age and sex matched cases treated with conventional medications (Group B). The
metabolic syndrome (MBS) was defined according to the International Diabetes
Foundation (IDF 2007 criteria for children). Increased waist circumference was
seen in 56.77% of cases in Group A. Triglyceridemia was less frequent in Group A.
MBS was higher in Group B [41.52% vs. 50.42%, odds ratio (OR) 1.76, 95% CI 1.19
2.41; p = .005]. Psoriasis is associated with higher prevalence of metabolic
syndrome in children. Six months of anti TNF treatment showed lesser association
with metabolic syndrome. With fasting blood glucose, and serum TG seen in
significantly lesser number of patients in this group.
PMID- 29334163
TI - Isomerically Pure Star-Shaped Triphenylene-Perylene Hybrids Involving Highly
Extended pi-Conjugation.
AB - The synthesis and characterization of a new type of a highly conjugated
heterocyclic pi-chromophore, consisting of a central triphenylene core fused with
three perylene monoimide units (star-shaped molecules), is described. By
judicious bay functionalization with tert-butylphenoxy substituents, aggregation
was completely prevented by using 1,1,2,2-tetrachloroethane, allowing for a
straightforward purification and, for the very first time, the complete
separation of the constitutional isomers by HPLC. Both isomers can be easily
distinguished by means of several conventional spectroscopic techniques.
Furthermore, we have illustrated the absence of supramolecular aggregates and
enhanced processability by noncovalent functionalization of graphene substrates,
showing an outstanding homogeneity and demonstrating a different doping behavior
in both isomers, making it possible to distinguish them by Raman spectroscopy.
PMID- 29334164
TI - Clinical evaluation of a novel fractional radiofrequency device for hair growth:
Fractional radiofrequency for hair growth stimulation.
AB - AGA is a common disorder. Different treatments are available to prevent hair loss
and achieve hair growth with variable results. The purpose of the present study
was to evaluate the efficacy and safety of a novel fractional radiofrequency (RF)
device (HairLux, Innogen Technologies Ltd., Yokneam, Israel), to prevent hair
loss and induce hair growth. Twenty-five patients received 10 fractional RF
treatments every 2 weeks, and were followed up 2 months after the last treatment.
All patients were evaluated by global photography. In 10 patients, blinded manual
hair counts were performed. Patients demonstrated less hair shedding, fuller
hair, and faster hair growth. There was an average increase of 31.6% in hair
density (based on hair counts) and 18% increase in hair shaft thickness. All
subjects tolerated the treatments well. The HairLux device is effective and safe
for hair growth stimulation in AGA. Ten treatment sessions are recommended to
maximize results.
PMID- 29334165
TI - 3D Printing of Liquid Crystal Elastomeric Actuators with Spatially Programed
Nematic Order.
AB - Liquid crystal elastomers (LCEs) are soft materials capable of large, reversible
shape changes, which may find potential application as artificial muscles, soft
robots, and dynamic functional architectures. Here, the design and additive
manufacturing of LCE actuators (LCEAs) with spatially programed nematic order
that exhibit large, reversible, and repeatable contraction with high specific
work capacity are reported. First, a photopolymerizable, solvent-free, main-chain
LCE ink is created via aza-Michael addition with the appropriate viscoelastic
properties for 3D printing. Next, high operating temperature direct ink writing
of LCE inks is used to align their mesogen domains along the direction of the
print path. To demonstrate the power of this additive manufacturing approach,
shape-morphing LCEA architectures are fabricated, which undergo reversible planar
to-3D and 3D-to-3D' transformations on demand, that can lift significantly more
weight than other LCEAs reported to date.
PMID- 29334166
TI - Investigating Nucleosome Accessibility for MNase, FeII Peplomycin, and
Duocarmycin B2 by Using Capillary Electrophoresis.
AB - Capillary electrophoresis, coupled with DNA 5' Texas Red labeling, was used to
investigate the ability of MNase, FeII peplomycin, and duocarmycin B2 to access
the nucleosome. Distinct accessibility patterns of these species to the
nucleosome were observed. MNase was completely prevented from approaching the
nucleosome core and exhibited a higher site specificity for targeting DNA sites
located close to the core region. Intercalation of peplomycin in the nucleosomal
core region was highly suppressed, but reaction sites located at the ends of the
nucleosomal core remained accessible, which implied flexibility of the core DNA
end. Duocarmycin B2 was able to enter and react in the core region, although its
alkylating efficiency decreased significantly.
PMID- 29334167
TI - Cross-Linking/Mass Spectrometry for Studying Protein Structures and Protein
Protein Interactions: Where Are We Now and Where Should We Go from Here?
AB - Structural mass spectrometry (MS) is gaining increasing importance for deriving
valuable three-dimensional structural information on proteins and protein
complexes, and it complements existing techniques, such as NMR spectroscopy and X
ray crystallography. Structural MS unites different MS-based techniques, such as
hydrogen/deuterium exchange, native MS, ion-mobility MS, protein footprinting,
and chemical cross-linking/MS, and it allows fundamental questions in structural
biology to be addressed. In this Minireview, I will focus on the cross-linking/MS
strategy. This method not only delivers tertiary structural information on
proteins, but is also increasingly being used to decipher protein interaction
networks, both in vitro and in vivo. Cross-linking/MS is currently one of the
most promising MS-based approaches to derive structural information on very large
and transient protein assemblies and intrinsically disordered proteins.
PMID- 29334168
TI - Representing causal knowledge in environmental policy interventions: Advantages
and opportunities for qualitative influence diagram applications.
AB - This article develops and explores a methodology for using qualitative influence
diagrams in environmental policy and management to support decision-making
efforts that minimize risk and increase resiliency. Influence diagrams are
representations of the conditional aspects of a problem domain. Their graphical
properties are useful for structuring causal knowledge relevant to policy
interventions and can be used to enhance inference and inclusivity of multiple
viewpoints. Qualitative components of influence diagrams are beneficial tools for
identifying and examining the interactions among the critical variables in
complex policy development and implementation. Policy interventions on social
environmental systems can be intuitively diagrammed for representing knowledge of
critical relationships among economic, environmental, and social attributes.
Examples relevant to coastal resiliency issues in the US Gulf Coast region are
developed to illustrate model structures for developing qualitative influence
diagrams useful for clarifying important policy intervention issues and enhancing
transparency in decision making. Integr Environ Assess Manag 2018;14:381-394.
Published 2018. This article is a US Government work and is in the public domain
in the USA.
PMID- 29334169
TI - Impact of baseline clinical and laboratory features on the risk of thrombosis in
children with acute lymphoblastic leukemia: A prospective evaluation.
AB - BACKGROUND: Children with acute lymphoblastic leukemia (ALL) have increased risk
of thromboembolism (TE). However, the predictors of ALL-associated TE are as yet
uncertain. OBJECTIVE: This exploratory, prospective cohort study evaluated the
effects of clinical (age, gender, ALL risk group) and laboratory variables
(hematological parameters, ABO blood group, inherited and acquired prothrombotic
defects [PDs]) at diagnosis on the development of symptomatic TE (sTE) in
children (aged 1 to <=18) treated on the Dana-Farber Cancer Institute ALL 05-001
study. PROCEDURES: Samples collected prior to the start of ALL therapy were
evaluated for genetic and acquired PDs (proteins C and S, antithrombin,
procoagulant factors VIII (FVIII:C), IX, XI and von Willebrand factor antigen
levels, gene polymorphisms of factor V G1691A, prothrombin gene G20210A and
methylene tetrahydrofolate reductase C677T, anticardiolipin antibodies, fasting
lipoprotein(a), and homocysteine). RESULTS: Of 131 enrolled patients (mean age
[range] 6.4 [1-17] years) 70 were male patients and 20 patients (15%) developed
sTE. Acquired or inherited PD had no impact on the risk of sTE. Multivariable
analyses identified older age (odds ratio [OR] 1.13; 95% confidence interval
[CI]: 1.01, 1.26) and non-O blood group (OR 3.64, 95% CI: 1.06, 12.51) as
independent predictors for development of sTE. Patients with circulating blasts
had higher odds of developing sTE (OR 6.66; 95% CI: 0.82, 53.85). CONCLUSION:
Older age, non-O blood group, and presence of circulating blasts, but not PDs,
predicted the risk of sTE during ALL therapy. We recommend evaluation of these
novel risk factors in the development of ALL-associated TE. If confirmed, these
easily accessible variables at diagnosis can help develop a risk-prediction model
for ALL-associated TE.
PMID- 29334170
TI - Representing causal knowledge in environmental policy interventions: Advantages
and opportunities for qualitative influence diagram applications.
AB - This article develops and explores a methodology for using qualitative influence
diagrams in environmental policy and management to support decision making
efforts that minimize risk and increase resiliency. Influence diagrams are
representations of the conditional aspects of a problem domain. Their graphical
properties are useful for structuring causal knowledge relevant to policy
interventions and can be used to enhance inference and inclusivity of multiple
viewpoints. Qualitative components of influence diagrams are beneficial tools for
identifying and examining the interactions among the critical variables in
complex policy development and implementation. Policy interventions on social
environmental systems can be intuitively diagrammed for representing knowledge of
critical relationships among economic, environmental, and social attributes.
Examples relevant to coastal resiliency issues in the U.S. Gulf Coast region are
developed to illustrate model structures for developing qualitative influence
diagrams useful for clarifying important policy intervention issues and enhancing
transparency in decision making. This article is protected by copyright. All
rights reserved.
PMID- 29334171
TI - Reaction Mechanism for Direct Cyclization of Linear C5 , C6 , and C7 Alkenes over
H-ITQ-13 Zeolite Investigated Using Density Functional Theory.
AB - Although dienes or trienes have been shown to be possible precursors for
cyclization, direct cyclization of alkenes or alkoxides has not been
systematically studied yet. Thus, the reaction mechanism of cyclization of linear
alkenes over H-ITQ-13 was investigated here by density functional theory
considering dispersive interactions (DFT-D). The similar free energy of different
linear alkoxides of the same carbon number suggests that they can co-exist in the
H-ITQ-13 intersection at 673.15 K during the methanol to olefins (MTO) process.
The formation of linear alkenes by olefins methylation with methoxyl groups
(ZOCH3 ), trimethyloxonium ions (TMO+ ), and methanol are kinetically more
favorable than by dimerization of olefins. Linear alkoxides or alkenes prefer
direct cyclization to cycloalkanes rather than hydride transfer to diene. This
study provides new insight into the alkene cyclization and aromatization
mechanisms in MTO process.
PMID- 29334172
TI - Silica Nanoparticle-induced Cytokine Responses in BEAS-2B and HBEC3-KT Cells:
Significance of Particle Size and Signalling Pathways in Different Lung Cell
Cultures.
AB - We have previously reported that silica nanoparticles (SiNPs) of nominal size 50
nm (Si50) induce the pro-inflammatory cytokines CXCL8 and IL-6 in BEAS-2B cells,
via mechanisms involving MAPK p38, TACE-mediated TGF-alpha release and the NF
kappaB pathway. In this study, we examined whether these findings are cell
specific or might be extended to another epithelial lung cell model, HBEC3-KT,
and also to SiNPs of a smaller size (nominal size of 10 nm; Si10). The TEM
average size of Si10 and Si50 was 10.9 and 34.7 nm, respectively. The surface
area (BET) of Si10 was three times higher than for Si50 per mass unit. With
respect to hydrodynamic size (DLS), Si10 in exposure medium showed a higher z
average for the main peak than Si50, indicating more excessive agglomeration.
Si10 strongly induced CXCL8 and IL-6, as assessed by ELISA and RT-PCR, and was
markedly more potent than Si50, even when adjusted to equal surface area.
Furthermore, Si10 was far more cytotoxic, measured as lactate dehydrogenase (LDH)
release, than Si50 in both epithelial cell cultures. With respect to signalling
pathways, Western analysis and experiments with and without inhibition of MAPK,
TACE and NF-kappaB (synthetic inhibitors) revealed that p38-phosphorylation, TACE
mediated TGF-alpha release and NF-kappaB activation seem to be important
triggering mechanisms for both Si50 and Si10 in the two different lung epithelial
cell cultures. In conclusion, the identified signalling pathways are suggested to
be important in inducing cytokine responses in different epithelial cell types
and also for various sizes of silica nanoparticles.
PMID- 29334173
TI - Microfluidic Templated Multicompartment Microgels for 3D Encapsulation and
Pairing of Single Cells.
AB - Controlled encapsulation and pairing of single cells within a confined 3D matrix
can enable the replication of the highly ordered cellular structure of human
tissues. Microgels with independently controlled compartments that can
encapsulate cells within separately confined hydrogel matrices would provide
precise control over the route of pairing single cells. Here, a one-step
microfluidic method is presented to generate monodisperse multicompartment
microgels that can be used as a 3D matrix to pair single cells in a highly
biocompatible manner. A method is presented to induce microgels formation on
chip, followed by direct extraction of the microgels from oil phase, thereby
avoiding prolonged exposure of the microgels to the oil. It is further
demonstrated that by entrapping stem cells with niche cells within separate but
adjacent compartments of the microgels, it can create complex stem cell niche
microenvironments in a controlled manner, which can serve as a useful tool for
the study of cell-cell interactions. This microfluidic technique represents a
significant step toward high-throughput single cells encapsulation and pairing
for the study of intercellular communications at single cell level, which is of
significant importance for cell biology, stem cell therapy, and tissue
engineering.
PMID- 29334174
TI - Trichloroacetic acid (80%) as a chemical debridement method for chronic venous
leg ulcers-A pilot study.
AB - Debridement is essential for the optimal care of venous leg ulcers. Several
debridement methods with different limitations may be deployed. Trichloroacetic
acid (TCA) is used for several dermatological purposes. Its application as a
chemical debridement method for leg ulcers has never been explored. We designed a
prospective study to determine the role of 80% TCA solution as a chemical
debridement method for leg ulcers, regarding efficacy and procedure-associated
pain. Chronic venous leg ulcers were treated with 3 cycles of 80% TCA solution or
curettage over 1 week. Pain and the mean percentage of fibrin and devitalized
tissue covering wound bed were evaluated. At the end of the study, a trend
towards larger fibrin mean reduction among the TCA treated ulcers was observed,
although this difference was not statistically significant (P = .35). The mean
pain score after TCA application was significantly reduced compared to pain after
curettage alone (P < 0.001). TCA presented several advantages over mechanical
debridement: it is a more selective debridement method, has haemostatic
properties, and a simpler and faster application. The 80% TCA solution may be a
cheap, simple, and considerably less-painful chemical debridement method for
venous leg ulcers compared to classical mechanical debridement.
PMID- 29334175
TI - Efficient Catalytic Oxidation of 5-Hydroxymethylfurfural to 2,5-Furandicarboxylic
Acid by Magnetic Laccase Catalyst.
AB - 2,5-Furandicarboxylic acid (FDCA) is a bio-based platform chemical for the
production of polyethylene furanoate (PEF) and other valuable furanic chemicals.
A magnetic laccase catalyst with (2,2,6,6-tetramethyl-piperidin-1-yl)oxyl (TEMPO)
as the mediator has the remarkable capability of oxidizing 5
hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA). Under optimal
reaction conditions, a quantitative yield (90.2 %) of FDCA with complete HMF
conversion was obtained after 96 h of reaction. More importantly, the magnetic
laccase catalyst exhibited good recyclability and stability, maintaining 84.8 %
of its original activity following six reuse cycles. This is the first report on
the efficient catalytic oxidation of HMF to FDCA by using an immobilized enzyme
catalyst.
PMID- 29334176
TI - The effect of 22.5 kHz low-frequency contact ultrasound debridement (LFCUD) on
lower extremity wound healing for a vascular surgery population: A randomised
controlled trial.
AB - The aim of this study was to compare changes in wound size and appearance and
health complication rates in patients with vasculopathy and lower-extremity
wounds treated with or without low-frequency contact ultrasound debridement
(LFCUD) This study was a randomised controlled trial. The study was conducted in
a vascular surgery service, including outpatient wound clinic and inpatient ward,
in a tertiary care academic centre. In total, 70 patients with vasculopathy and
lower-extremity wounds of mixed aetiology were enrolled in the trial; 68
completed the study. Patients were randomised to receive LFCUD plus usual care (n
= 33) or usual care (n = 37) at 4 weekly visits, and were followed thereafter for
up to 12 wk. The main outcome measures included closed wounds, change in wound
surface area (WSA), and wound appearance by the revised Photographic Wound
Assessment Tool (revPWAT). After 4 weekly LFCUD treatments, patients in the LFCUD
group had significantly better wound appearance (total revPWAT score) compared
with the control group treated only with usual care (P = <0.05). LFCUD-treated
wounds also had a significant reduction in WSA over 4 wk that was not found in
the UC group. LFCUD treatment was also associated with a greater number of healed
wounds, odds ratio 5.00 (95% CI 1.24-20.25), and fewer instances of wound
deterioration. Weekly LFCUD applications to patients with significant
vasculopathy resulted in superior healing outcomes when compared with current
usual wound care practice.
PMID- 29334177
TI - Polypropylene Nonwoven Fabric@Poly(ionic liquid)s for Switchable Oil/Water
Separation, Dye Absorption, and Antibacterial Applications.
AB - Pollutants in wastewater include oils, dyes, and bacteria, making wastewater
cleanup difficult. Multifunctional wastewater treatment media consisting of
poly(ionic liquid)-grafted polypropylene (PP) nonwoven fabrics (PP@PIL) are
prepared by a simple and scalable surface-grafting process. The fabricated PP@PIL
fabrics exhibit impressive switchable oil/water separation (eta>99 %) and dye
absorption performance (q=410 mg g-1 ), as well as high antibacterial properties.
The oil/water separation can be easily switched by anion exchanging of the PIL
segments. Moreover, the multiple functions (oil/water separation, dye absorption,
and antibacterial properties) occurred at the same time, and did not interfere
with each other. The multifunctional fibrous filter can be easily regenerated by
washing with an acid solution, and the absorption capacity is maintained after
many recycling tests. These promising features make PIL-grafted PP nonwoven
fabric a potential one-step treatment for multicomponent wastewater.
PMID- 29334178
TI - Factors associated with perceived accuracy of the Undetectable = Untransmittable
slogan among men who have sex with men: Implications for messaging scale-up and
implementation.
AB - INTRODUCTION: Recent research has shown high efficacy of HIV treatment for
reducing the risk of HIV transmission to sexual partners. As the efficacy of
treatment as prevention (TasP) has proliferated, a new messaging campaign,
Undetectable = Untransmittable, has been gaining popularity. The purpose of this
paper was to assess factors associated with the perceived accuracy of this TasP
messaging strategy among a large and diverse sample of gay, bisexual, and other
men who have sex with men (GBMSM) in order to inform subsequent efforts at large
scale and implementation of the HIV prevention message. METHODS: We conducted a
nationwide survey of GBMSM in the U.S. recruited from an online social networking
site and a mobile sexual networking app. We analysed data from 12,222 GBMSM
separately by HIV status to examine sociodemographic and behavioural factors
associated with ratings of the accuracy of the Undetectable = Untransmittable
message, which included the option to indicate not understanding what
"undetectable" meant. RESULTS: Among HIV-negative and unknown men, multivariable
linear regression indicated that being on pre-exposure prophylaxis (PrEP),
identifying as gay or queer (versus bisexual or straight), recent serodiscordant
condomless anal sex (CAS), testing every six months or more often, less concern
about sexually transmitted infection (STI) infection, and lower perceived risk of
HIV infection were the factors with the largest independent effect on rating the
Undetectable = Untransmittable statement as more accurate. Fewer factors emerged
as associated with accuracy ratings among HIV-positive participants-reporting an
undetectable viral load, a lifetime acquired immune deficiency syndrome (AIDS)
diagnosis, and lower concern about STI infection were the factors most strongly
associated with rating the statement as more accurate. CONCLUSIONS: The findings
of the current study highlight variability in the perceived accuracy of the
Undetectable = Untransmittable message, suggesting potential subgroups who might
benefit from targeted educational campaigns, perhaps broadcast utilizing sexual
networking apps. Numerous factors, particularly among HIV-negative and unknown
GBMSM, were associated with rating the message as more accurate. In particular,
being on PrEP and testing regularly were two of the variables most strongly
associated with higher accuracy ratings among HIV-negative GBMSM, suggesting HIV
prevention services as potential points of intervention for increasing HIV
knowledge and decreasing HIV stigma.
PMID- 29334179
TI - Functionalized Nanoparticles Efficiently Enhancing the Targeted Delivery, Tumor
Penetration, and Anticancer Activity of 7-Ethyl-10-Hydroxycamptothecin.
AB - The enhanced permeability and retention (EPR) effect of tumors is much more
complex than initially defined, and it alone is not sufficient for targeted
delivery of nanosized agents. Meanwhile, poor tumor penetration is another major
challenge for the treatment of solid tumors using nanoparticles. Development of
delivery systems for SN38, the active metabolite of CPT-11 in human and a very
potent anticancer molecule, has become an attractive research area. PEGx
p(HEMASN38)y (x and y are viable), a prodrug synthesized by using polyethylene
glycol (PEG) as initiator and SN38 as monomer through atom transfer radical
polymeration (ATRP) method, is previously reported. Using PEG2.4K -p(HEMASN38)3K
as a model prodrug, herein an active-targeted strategy decorated with cys-arg-gly
asp-lys (CRGDK), a peptide specifically binds to neuropilin-1 overexpressed by
tumor vessels and tumor cells, is successfully established to further improve the
delivery and efficacy of SN38. CRGDK-functionalized PEG2.4K -p(HEMASN38)3K (C
SN38) nanoparticles and nonfunctionalized control (B-SN38) are prepared with two
distinct sizes, 30 and 100 nm. Their physiochemical and biological
characteristics are investigated in vitro and in vivo with multiple tumor models.
It is demonstrated for the first time that CRGDK functionalization can be a
promising strategy for efficient delivery of SN38, and C-SN38 is a potent drug
candidate for the treatment of neuropilin-1 overexpressing tumors.
PMID- 29334180
TI - Nitric Oxide Dependent Degradation of Polyethylene Glycol-Modified Single-Walled
Carbon Nanotubes: Implications for Intra-Articular Delivery.
AB - Polyethylene glycol (PEG)-modified carbon nanotubes have been successfully
employed for intra-articular delivery in mice without systemic or local toxicity.
However, the fate of the delivery system itself remains to be understood. In this
study 2 kDa PEG-modified single-walled carbon nanotubes (PNTs) are synthesized,
and trafficking and degradation following intra-articular injection into the knee
joint of healthy mice are studied. Using confocal Raman microspectroscopy, PNTs
can be imaged in the knee-joint and are found to either egress from the synovial
cavity or undergo biodegradation over a period of 3 weeks. Raman analysis
discloses that PNTs are oxidatively degraded mainly in the chondrocyte-rich
cartilage and meniscus regions while PNTs can also be detected in the synovial
membrane regions, where macrophages can be found. Furthermore, using murine
chondrocyte (ATDC-5) and macrophage (RAW264.7) cell lines, biodegradation of PNTs
in activated, nitric oxide (NO)-producing chondrocytes, which is blocked upon
pharmacological inhibition of inducible nitric oxide synthase (iNOS), can be
shown. Biodegradation of PNTs in macrophages is also noted, but after a longer
period of incubation. Finally, cell-free degradation of PNTs upon incubation with
the peroxynitrite-generating compound, SIN-1 is demonstrated. The present study
paves the way for the use of PNTs as delivery systems in the treatment of
diseases of the joint.
PMID- 29334181
TI - Donor Variability in Growth Kinetics of Healthy hMSCs Using Manual Processing:
Considerations for Manufacture of Cell Therapies.
AB - Human mesenchymal stromal cells (hMSCs) are excellent candidates for cell therapy
but their expansion to desired clinical quantities can be compromised by ex vivo
processing, due to differences between donor material and process variation. The
aim of this article is to characterize growth kinetics of healthy baseline
"reference" hMSCs using typical manual processing. Bone-marrow derived hMSCs from
ten donors are isolated based on plastic adherence, expanded, and analyzed for
their growth kinetics until passage 4. Results indicate that hMSC density
decreases with overall time in culture (p < 0.001) but no significant differences
are observed between successive passages after passage 1. In addition, fold
increase in cell number dropped between passage 1 and 2 for three batches, which
correlated to lower performance in total fold increase and expansion potential of
these batches, suggesting that proliferative ability of hMSCs can be predicted at
an early stage. An indicative bounded operating window is determined between
passage 1 and 3 (PDL < 10), despite the high inter-donor variability present
under standardized hMSC expansion conditions used. hMSC growth profile analysis
will be of benefit to cell therapy manufacturing as a tool to predict culture
performance and attainment of clinically-relevant yields, therefore stratifying
the patient population based on early observation.
PMID- 29334182
TI - Designing 3D Biological Surfaces via the Breath-Figure Method.
AB - The fabrication of biointerfaces that mimic cellular physiological environments
is critical to understanding cell behaviors in vitro and for the design of tissue
engineering. Breath figure is a self-assemble method that uses water droplets
condensed from moisture as template and ends up with a highly ordered hexagonal
pore array; this approach is used to fabricate various biological substrates.
This progress report provides an overview of strategies to achieve topographical
modifications and chemical-patterned arrays, such as modulation of the pore size,
shape and selective decoration of the honeycomb holes. Using recent results in
the biological fields, potential future applications and developments of
honeycomb structures are commented upon.
PMID- 29334183
TI - Engineering Polymersomes for Diagnostics and Therapy.
AB - Engineered polymer vesicles, termed as polymersomes, confer a flexibility to
control their structure, properties, and functionality. Self-assembly of
amphiphilic copolymers leads to vesicles consisting of a hydrophobic bilayer
membrane and hydrophilic core, each of which is loaded with a wide array of small
and large molecules of interests. As such, polymersomes are increasingly being
studied as carriers of imaging probes and therapeutic drugs. Effective delivery
of polymersomes necessitates careful design of polymersomes. Therefore, this
review article discusses the design strategies of polymersomes developed for
enhanced transport and efficacy of imaging probes and therapeutic drugs. In
particular, the article focuses on overviewing technologies to regulate the size,
structure, shape, surface activity, and stimuli- responsiveness of polymersomes
and discussing the extent to which these properties and structure of polymersomes
influence the efficacy of cargo molecules. Taken together with future
considerations, this article will serve to improve the controllability of
polymersome functions and accelerate the use of polymersomes in biomedical
applications.
PMID- 29334184
TI - pH-Responsive PEG-Doxorubicin-Encapsulated Aza-BODIPY Nanotheranostic Agent for
Imaging-Guided Synergistic Cancer Therapy.
AB - Synergistic cancer therapy is of great interest for multiple advantages, such as
excellent targeting accuracy, low side effects, and enhanced therapeutic
efficiency. Herein, a near-infrared photosensitizer aza-BODIPY (AB) with high
singlet oxygen quantum yield (PhiDelta = 82%) is designed and synthesized. With
Schiff's base obtained from condensation reaction between doxorubicin (DOX) and
polyethylene glycol-benzaldehyde (PEG-CHO) as the polymer matrix, aza-BODIPY is
encapsulated to afford hydrophilic nanoparticles (DAB NPs). The DAB NPs exhibit
high reactive oxygen species (ROS) generation rate and outstanding photothermal
conversion efficiency (eta = 38.3%) under irradiation. In vivo fluorescence- and
photothermal-imaging (PTI) results demonstrate that DAB NPs can specifically
accumulate at tumor sites and serve as dual-modal imaging probe for cancer
diagnosis. Particularly, triggered by acidic tumor microenvironment, the ?HC?N?
bond of Schiff's base would be broken simultaneously, resulting in the efficient
release of DOX from DAB NPs at tumor sites as well as enhancing the targeting
performance of chemotherapeutics. Compared with free DOX and aza-BODIPY
nanoparticles, DAB NPs can inhibit tumor growth more effectively through pH
responsive photodynamic/photothermal/chemo synergistic therapy. This report may
also present a practicable strategy to develop a pH-responsive nanotheranostic
agent for tumor targeting, imaging, and therapy.
PMID- 29334185
TI - Physical Properties of Implanted Porous Bioscaffolds Regulate Skin Repair:
Focusing on Mechanical and Structural Features.
AB - Porous bioscaffolds are applied to facilitate skin repair since the early 1990s,
but a perfect regeneration outcome has yet to be achieved. Until now, most
efforts have focused on modulating the chemical properties of bioscaffolds, while
physical properties are traditionally overlooked. Recent advances in
mechanobiology and mechanotherapy have highlighted the importance of
biomaterials' physical properties in the regulation of cellular behaviors and
regenerative processes. In skin repair, the mechanical and structural features of
porous bioscaffolds are two major physical properties that determine therapeutic
efficacy. Here, first an overview of natural skin repair with an emphasis on the
major biophysically sensitive cell types involved in this multistage process is
provided, followed by an introduction of the four roles of bioscaffolds as skin
implants. Then, how the mechanical and structural features of bioscaffolds
influence these four roles is discussed. The mechanical and structural features
of porous bioscaffolds should be tailored to balance the acceleration of wound
closure and functional improvements of the repaired skin. This study emphasizes
that decoupling and precise control of the mechanical and structural features of
bioscaffolds are significant aspects that should be considered in future
biomaterial optimization, which can build a foundation to ultimately achieve
perfect skin regeneration outcomes.
PMID- 29334186
TI - Natural Humic-Acid-Based Phototheranostic Agent.
AB - Humic acids, a major constituent of natural organic carbon resources, are
naturally formed through the microbial biodegradation of animal and plant
residues. Due to numerous physiologically active groups (phenol, carboxyl, and
quinone), the biomedical applications of humic acid have been already
investigated across different cultures for several centuries or even longer. In
this work, sodium humate, the sodium salt of humic acid, is explored as
phototheranostic agent for light-induced photoacoustic imaging and photothermal
therapy based on intrinsic absorption in the near-infrared region. The purified
colloidal sodium humate exhibits a high photothermal conversion efficiency up to
76.3%, much higher than that of the majority of state-of-the-art photothermal
agents including gold nanorods, Cu9 S5 nanoparticles, antimonene quantum dots,
and black phosphorus quantum dots, leading to obvious photoacoustic enhancement
in vitro and in vivo. Besides, highly effective photothermal ablation of HeLa
tumor is achieved through intratumoral injection. Impressively, sodium humate
reveals ultralow toxicity at the cellular and animal levels. This work promises
the great potential of humic acids as light-mediated theranostic agents, thus
expanding the application scope of traditional humic acids in biomedical field.
PMID- 29334188
TI - Soft Artificial Bladder Detrusor.
AB - Developing soft devices for invasive procedures bears great importance for human
health. The softness and large strain actuation of responsive hydrogels promise
the potential to fabricate soft devices, which can attach on and assist to the
function of organs. The key challenges lie in the fabrication of soft devices
with robust actuating ability and biocompatibility to the attached organ. This
paper presents a solution that integrates the thermoresponsive hydrogel membrane
with flexible electronics and silk scaffold into a balloon-like soft device. As
an example, the actuation assisting function of this soft device for shrinking an
animal bladder is presented. The mechanical behaviors of the balloon-like soft
device are experimentally and theoretically investigated. The concepts are
applicable to other applications such as soft implants, soft robotics, and
microfluidics.
PMID- 29334189
TI - A Multifunctional Micellar Nanoplatform with pH-Triggered Cell Penetration and
Nuclear Targeting for Effective Cancer Therapy and Inhibition to Lung Metastasis.
AB - The enhancement of cellular internalization and subsequent achievement of a
nuclear targeting of nanocarriers play an important role in maximizing the
therapeutic potency and minimizing the side effects of encapsulated drugs.
Herein, a multifunctional micellar nanoplatform simultaneously with high cell
penetration and nuclear targeting through pH-triggered surface charge reversal is
presented. The miscellar system is constructed from poly(ethylene glycol)
poly(epsilon-caprolactone) with 2,3-dimethylmaleic anhydride-Tat decoration
(PECL/DA-Tat). DA groups are used to mask the positive charge of Tat to prolong
blood circulation of the nanocarriers. In the mildly acidic environment of tumor
tissue, the system exhibits ultrasensitive negative to positive charge reversal,
facilitating the cell internalization and subsequent nuclear targeting. The
chemotherapeutic 10-hydroxycamptothecin conjugated to methoxy polyethylene
glycol, which is loaded in this micelle, obviously enhances cytotoxicity against
tumor cells. The in vivo therapy in mice bearing 4T1 breast tumor reveals that
the system has a significant enhancement of both the endocytosis and nuclear
enrichment, showing a highly effective antitumor efficacy and inhibition to lung
metastasis.
PMID- 29334187
TI - Surveying the landscape of optogenetic methods for detection of protein-protein
interactions.
AB - Mapping the protein-protein interaction (PPi) landscape is of critical importance
to furthering our understanding how cells and organisms function. Optogenetic
methods, that is, approaches that utilize genetically encoded fluorophores or
fluorogenic enzyme reactions, uniquely enable the visualization of biochemical
phenomena in live cells with high spatial and temporal accuracy. Applying
optogenetic methods to the detection of PPis requires the engineering of protein
based systems in which an optical signal undergoes a substantial change when the
two proteins of interest interact. In recent years, researchers have developed a
number of creative and effective optogenetic methods that achieve this goal, and
used them to further elaborate our map of the PPi landscape. In this review, we
provide an introduction to the general principles of optogenetic PPi detection,
and then provide a number of representative examples of how these principles have
been applied. We have organized this review by categorizing methods based on
whether the signal generated is reversible or irreversible in nature, and whether
the signal is localized or nonlocalized at the subcellular site of the PPi. We
discuss these techniques giving both their benefits and drawbacks to enable
rational choices about their potential use. This article is categorized under:
Laboratory Methods and Technologies > Imaging Laboratory Methods and Technologies
> Macromolecular Interactions, Methods Analytical and Computational Methods >
Analytical Methods.
PMID- 29334190
TI - The effects of low levels of trivalent ions on a standard strain of Escherichia
coli (ATCC 11775) in aqueous solutions.
AB - Considering the ever-growing usage of trivalent salts in water treatment, for
example, lanthanum salts in rare earth, AlCl3 and FeCl3 , the effects of
different trivalent cations on the bacterium Escherichia coli (E. coli) ATCC
11775 strain have been studied in aqueous solutions. From colony incubation
studies, the colony-forming unit (CFU) densities were found to decrease
significantly in the presence of even low levels (10-5 mol/L) of lanthanum
chloride. This level of reduction in CFU number is comparable to the results
obtained using the known bacteriocidal cationic surfactant, C14 TAB. By
comparison, exposure of the cells to low levels of trivalent ion, aluminum and
chromium ion solutions produced only modest reductions in CFU density. The
results from the incubation studies suggest that the bacteriostatic mechanism of
La3+ ions has similarities to that of the cationic surfactant, and different to
that of the other trivalent ions. Size distribution and zeta potential
measurements of E. coli cells and phospholipid vesicles in the presence of
trivalent cations solutions suggested significant cell shrinkage probably caused
by membrane disruption.
PMID- 29334191
TI - Exogenous oestrogen inhibits genital transmission of cell-associated HIV-1 in
DMPA-treated humanized mice.
AB - INTRODUCTION: HIV affects more women than any other life-threatening infectious
agent, and most infections are sexually transmitted. HIV must breach the female
genital tract mucosal barrier to establish systemic infection, and clinical
studies indicate virus more easily evades this barrier in women using depot
medroxyprogesterone acetate (DMPA) and other injectable progestins for
contraception. Identifying a potential mechanism for this association, we learned
DMPA promotes susceptibility of wild-type mice to genital herpes simplex virus
type 2 (HSV-2) infection by reducing genital tissue expression of the cell-cell
adhesion molecule desmoglein-1 (DSG-1) and increasing genital mucosal
permeability. Conversely, DMPA-mediated increases in genital mucosal permeability
and HSV-2 susceptibility were eliminated in mice concomitantly administered
exogenous oestrogen (E). To confirm and extend these findings, herein we used
humanized mice to define effects of systemic DMPA and intravaginal (ivag) E
administration on susceptibility to genital infection with cell-associated HIV-1.
METHODS: Effects of DMPA or an intravaginal (ivag) E cream on engraftment of NOD
scid-IL-2Rgcnull (NSG) mice with human peripheral blood mononuclear cells
(hPBMCs) were defined with flow cytometry. Confocal microscopy was used to
evaluate effects of DMPA, DMPA and E cream, or DMPA and the pharmacologically
active component of the cream on vaginal tissue DSG-1 expression and genital
mucosal permeability to low molecular weight (LMW) molecules and hPBMCs. In other
studies, hPBMC-engrafted NSG mice (hPBMC-NSG) received DMPA or DMPA and ivag E
cream before genital inoculation with 106 HIV-1-infected hPBMCs. Mice were
euthanized 10 days after infection, and plasma HIV-1 load quantified by qRT-PCR
and splenocytes used to detect HIV-1 p24 antigen via immunohistochemistry and
infectious virus via TZM-bl luciferase assay. RESULTS: Whereas hPBMC engraftment
was unaffected by DMPA or E treatment, mice administered DMPA and E (cream or the
pharmacologically active cream component) displayed greater vaginal tissue
expression of DSG-1 protein and decreased vaginal mucosal permeability to LMW
molecules and hPBMCs versus DMPA-treated mice. DMPA-treated hPBMC-NSG mice were
also uniformly susceptible to genital transmission of cell-associated HIV-1,
while no animal concomitantly administered DMPA and E cream acquired systemic HIV
1 infection. CONCLUSION: Exogenous E administration reduces susceptibility of
DMPA-treated humanized mice to genital HIV-1 infection.
PMID- 29334192
TI - Digitalizing Self-Assembled Chiral Superstructures for Optical Vortex Processing.
AB - Cholesteric liquid crystal (CLC) chiral superstructures exhibit unique features;
that is, polychromatic and spin-determined phase modulation. Here, a concept for
digitalized chiral superstructures is proposed, which further enables the
arbitrary manipulation of reflective geometric phase and may significantly
upgrade existing optical apparatus. By encoding a specifically designed binary
pattern, an innovative CLC optical vortex (OV) processor is demonstrated. Up to
25 different OVs are extracted with equal efficiency over a wavelength range of
116 nm. The multiplexed OVs can be detected simultaneously without mode crosstalk
or distortion, permitting a polychromatic, large-capacity, and in situ method for
parallel OV processing. Such complex but easily fabricated self-assembled chiral
superstructures exhibit versatile functionalities, and provide a satisfactory
platform for OV manipulation and other cutting-edge territories. This work is a
vital step towards extending the fundamental understanding and fantastic
applications of ordered soft matter.
PMID- 29334193
TI - Managing risk of surgical procedures in pediatric transplant recipients taking
mTOR inhibitors: What is the optimal strategy?
PMID- 29334194
TI - Enrollment in early-phase clinical trials in pediatric oncology: The experience
at Institut Curie.
AB - BACKGROUND: The European Paediatric Regulation was introduced in 2007 to
facilitate access to new medicines for children. Our study explored accessibility
of early-phase trials in pediatric oncology, in line with the European Paediatric
Regulation, to identify the reasons for not inviting patients to participate,
parents' refusal, or inclusion failure. PROCEDURE: We conducted a retrospective
chart review at Institut Curie, Paris, for all pediatric patients whose cancer
progressed despite known effective treatments between July 2010 and December
2013. RESULTS: Out of 100 patients in the palliative phase, 52 received one or
more invitations to participate in early-phase trials. Twenty parents declined
the invitation, mainly prioritizing quality of life or fearing constraints.
Fourteen inclusions failed despite parental approval, mostly due to rapid
clinical deterioration. Five patients received no invitations because no early
phase trials were available. Major reasons for noninclusion in the 43 remaining
patients were presence of exclusion criteria or other physical factors,
preference for conventional treatment, constraints, psychological factors, and
follow-up in another hospital after moving. CONCLUSIONS: The Paediatric
Regulation has led to increased availability of early-phase trials. Better timing
of the proposal, designing less constraining early-phase trials, reducing waiting
lists, and improving information for parents and children would facilitate
pediatric access to new medicines.
PMID- 29334195
TI - Exoproteome Profiling Reveals the Involvement of the Foldase PrsA in the Cell
Surface Properties and Pathogenesis of Staphylococcus aureus.
AB - Staphylococcus aureus is a bacterial pathogen that produces and exports many
virulence factors that cause diseases in humans. PrsA, a membrane-bound foldase,
is expressed ubiquitously in Gram-positive bacteria and required for the folding
of exported proteins into a stable and active structure. To understand the
involvement of PrsA in posttranslocational protein folding in S. aureus, a PrsA
deficient mutant of S. aureus HG001 was constructed. Using isobaric tags for
relative and absolute quantification (iTRAQ)-based mass spectrometry analyses,
the exoproteomes of PrsA mutant and wild type S. aureus were comparatively
profiled, and 163 cell wall-associated proteins and 67 exoproteins with altered
levels have been identified in the PrsA-deficient mutant. Bioinformatics analyses
further reveal that prsA deletion altered the amounts of proteins that are
potentially involved in the regulation of cell surface properties and bacterial
pathogenesis. To determine the relevancy of our findings, we investigated the
functional consequence of prsA deletion in S. aureus. PrsA deficiency can enhance
bacterial autoaggregation and increase the adhesion ability of S. aureus to human
lung epithelial cells. Moreover, mice infected with PrsA-deficient S. aureus had
a better survival rate compared with those infected with the wild-type S. aureus.
Collectively, our findings reveal that PrsA is required for the
posttranslocational folding of numerous exported proteins and critically affects
the cell surface properties and pathogenesis of S. aureus.
PMID- 29334196
TI - Microfluidic Tumor-Vascular Model to Study Breast Cancer Cell Invasion and
Intravasation.
AB - Cancer is a major leading cause of disease-related death in the world. The severe
impact of cancer can be attributed to poor understanding of the mechanisms
involved in earliest steps of the metastatic cascade, specifically invasion into
the surrounding stroma and intravasation into the blood capillaries. However,
conducting integrated biological studies of invasion and intravasation have been
challenging, within in vivo models and traditional in vitro assay, due to
difficulties in establishing a precise tumor microenvironment. To that end, in
this work, a novel 3D microfluidic platform comprised of concentric three-layer
cell-laden hydrogels for simultaneous investigation of breast cancer cell
invasion and intravasation as well as vasculature maturation influenced by tumor
vascular crosstalk is developed. It was demonstrated that the presence of
spontaneously formed vasculature enhance MDA-MB-231 invasion into the 3D stroma.
Following invasion, cancer cells are visualized intravasating into the outer
vasculature. Additionally, invading cancer cells significantly reduce vessel
diameter while increasing permeability, consistent with previous in vivo studies.
Major signaling cytokines involved in tumor-vascular crosstalk that govern cancer
cell invasion and intravasation are further identified. Taken together, this
platform will enable unique insights of critical biological events within the
metastatic cascade, with significant potential for developing efficient cancer
therapeutics.
PMID- 29334198
TI - Enzyme-Based Glucose Sensor: From Invasive to Wearable Device.
AB - Blood glucose concentration is a key indicator of patients' health, particularly
for symptoms associated with diabetes mellitus. Because of the large number of
diabetic patients, many approaches for glucose measurement have been studied to
enable continuous and accurate glucose level monitoring. Among them,
electrochemical analysis is prominent because it is simple and quantitative. This
technology has been incorporated into commercialized and research-level devices
from simple test strips to wearable devices and implantable systems. Although
directly monitoring blood glucose assures accurate information, the invasive
needle-pinching step to collect blood often results in patients (particularly
young patients) being reluctant to adopt the process. An implantable glucose
sensor may avoid the burden of repeated blood collections, but it is quite
invasive and requires periodic replacement of the sensor owing to biofouling and
its short lifetime. Therefore, noninvasive methods to estimate blood glucose
levels from tears, saliva, interstitial fluid (ISF), and sweat are currently
being studied. This review discusses the evolution of enzyme-based
electrochemical glucose sensors, including materials, device structures,
fabrication processes, and system engineering. Furthermore, invasive and
noninvasive blood glucose monitoring methods using various biofluids or blood are
described, highlighting the recent progress in the development of enzyme-based
glucose sensors and their integrated systems.
PMID- 29334197
TI - Increased non-AIDS mortality among persons with AIDS-defining events after
antiretroviral therapy initiation.
AB - INTRODUCTION: HIV-1 infection leads to chronic inflammation and to an increased
risk of non-AIDS mortality. Our objective was to determine whether AIDS-defining
events (ADEs) were associated with increased overall and cause-specific non-AIDS
related mortality after antiretroviral therapy (ART) initiation. METHODS: We
included HIV treatment-naive adults from the Antiretroviral Therapy Cohort
Collaboration (ART-CC) who initiated ART from 1996 to 2014. Causes of death were
assigned using the Coding Causes of Death in HIV (CoDe) protocol. The adjusted
hazard ratio (aHR) for overall and cause-specific non-AIDS mortality among those
with an ADE (all ADEs, tuberculosis (TB), Pneumocystis jiroveci pneumonia (PJP),
and non-Hodgkin's lymphoma (NHL)) compared to those without an ADE was estimated
using a marginal structural model. RESULTS: The adjusted hazard of overall non
AIDS mortality was higher among those with any ADE compared to those without any
ADE (aHR 2.21, 95% confidence interval (CI) 2.00 to 2.43). The adjusted hazard of
each of the cause-specific non-AIDS related deaths were higher among those with
any ADE compared to those without, except metabolic deaths (malignancy aHR 2.59
(95% CI 2.13 to 3.14), accident/suicide/overdose aHR 1.37 (95% CI 1.05 to 1.79),
cardiovascular aHR 1.95 (95% CI 1.54 to 2.48), infection aHR (95% CI 1.68 to
2.81), hepatic aHR 2.09 (95% CI 1.61 to 2.72), respiratory aHR 4.28 (95% CI 2.67
to 6.88), renal aHR 5.81 (95% CI 2.69 to 12.56) and central nervous aHR 1.53 (95%
CI 1.18 to 5.44)). The risk of overall and cause-specific non-AIDS mortality
differed depending on the specific ADE of interest (TB, PJP, NHL). CONCLUSIONS:
In this large multi-centre cohort collaboration with standardized assignment of
causes of death, non-AIDS mortality was twice as high among patients with an ADE
compared to without an ADE. However, non-AIDS related mortality after an ADE
depended on the ADE of interest. Although there may be unmeasured confounders,
these findings suggest that a common pathway may be independently driving both
ADEs and NADE mortality. While prevention of ADEs may reduce subsequent death due
to NADEs following ART initiation, modification of risk factors for NADE
mortality remains important after ADE survival.
PMID- 29334199
TI - Comparison of Cabergoline and Quinagolide in Prevention of Severe Ovarian
Hyperstimulation Syndrome among Patients Undergoing Intracytoplasmic Sperm
Injection.
AB - Background: The aim of the current study is to compare quinagolide with
cabergoline in prevention of ovarian hyperstimulation syndrome (OHSS) among high
risk women undergoing intracytoplasmic sperm injection (ICSI). MATERIALS AND
METHODS: This randomized clinical trial study was performed from March 2015 to
February 2017. One hundred and twenty six women undergoing ICSI who were at high
risk of developing OHSS (having over 20 follicles of >12 mm), were randomized
into two groups. The first group received cabergoline 0.5 mg and the second group
received quinagolide 75 mg every day for 7 days commencing on the day of
gonadotropin-releasing hormone (GnRH) agonist administration. Then OHSS symptoms
as well as their severity were assessed according to standard definition, 3 and 6
days after GnRH agonist administration. Ascites were determined by trans-vaginal
ultrasound. Other secondary points were the number of oocytes and the number of
embryos and their quality. Quantitative and qualitative data were analyzed using
Student's t test, and Chi-square or fisher's exact test, respectively. A P<0.05
was considered statistically significant. RESULTS: The incidence of severe OHSS
in the quinagolide-treated group was 3.1% while it was 15.8% in
cabergolinetreated subjects (P<0.001). Ascites were less frequent after treatment
with Quinagolide as compared to cabergoline (21.9% vs. 61.9%, respectively)
(P=0.0001). There was no significant statistical deferences between the two
groups in terms of mean age, number of oocytes, metaphase I and metaphase II
oocytes, and germinal vesicles. There was a significant difference between
cabergoline and quinagolide groups regarding the embryo number (P=0.037) with
cabergoline-treated group showing a higher number of embryos. But, the number of
good quality embryo in quinagolide- treated individuals was significantly higher
than that of the cabergoline-treated group (P=0.001). CONCLUSION: Quinagolide
seems to be more effective than Cabergoline in prevention of OHSS in high-risk
patients undergoing ICSI. (Registration number: IRCT2016053128187N1).
PMID- 29334200
TI - Comparative Effectiveness of Antidepressant Medication versus Psychological
Intervention on Depression Symptoms in Women with Infertility and Sexual
Dysfunction.
AB - Background: Fertility loss is considered as a challenging experience. This study
was conducted to compare the effectiveness of antidepressant medication and
psychological intervention on depression symptoms in women with infertility and
sexual dysfunctions (SD). MATERIALS AND METHODS: This randomized, controlled
clinical trial study was completed from December 2014 to June 2015 in Babol,
Iran. Of the 485 participants, 93 were randomly assigned in a 1:1:1 ratio to
psychosexual therapy (PST), bupropion extended-release (BUP ER) at a dose of 150
mg/d, and control (no intervention) groups. The beck depression inventory (BDI)
was completed at the beginning and end of the study. Duration of study was eight
weeks. Statistical analyses were performed by using paired-test and analysis of
covariance. RESULTS: The mean depression score on the BDI was 22.35 +/- 8.70 in
all participants. Mean BDI score decreased significantly in both treatment groups
(PST: P<0.0001, BUP: P<0.002) from baseline to end of the study, whereas intra
individual changes in BDI score were not significant in the control group. The
decrease in mean BDI score was greater with PST compared to BUP treatment
(P<0.005) and the control group (P<0.0001). The PST group showed greater
improvement in depression levels (severe to moderate, moderate to mild) in
comparison with the two other groups (P<0.001). Drug treatment was well tolerated
by the participants in the BUP group. CONCLUSION: PST can be a reliable
alternative to BUP ER for relieving depression symptoms in an Iranian population
of women with infertility and SD (Registration number: IRCT2015042721955N2).
PMID- 29334201
TI - Comparison of The Effects of A Positive Reappraisal Coping Intervention and
Problem-Solving Skills Training on Depression during The Waiting Period of The
Result of Intrauterine Insemination Treatment: A Randomized Control Trial.
AB - Background: The outcomes of fertility treatments are unpredictable, and levels of
depressive symptoms increase in patients during the waiting period of the result
of intrauterine insemination (IUI) treatment. The aim of this study was to
compare the effects of a positive reappraisal coping intervention (PRCI) and
problem-solving skills training (PSS) on depression during the waiting period of
the result of IUI Treatment. MATERIALS AND METHODS: This randomized control
clinical trial was done among 108 women undergoing IUI treatment. In the control
group, the women received routine care. In the PRCI group, women attended two
training sessions and were asked to complete coping thoughts cards and fill out
daily monitoring forms during the waiting period. In the PSS group, PSS were
taught over three sessions. The depression was measured by the beck depression
inventory. RESULTS: On the 10thth day of the IUI waiting period, there were
significant differences between the control group (21.42 +/- 11.42) and the PSS
group (12.52 +/- 8.05) and PRCI groups (13.14 +/- 9.7) (P<0.001), but no
significant difference between the PRCI group and the PSS group. CONCLUSION:
According to the results of this randomized control trial there is no difference
between a PRCI and PSS on depression during the waiting period of the result of
IUI treatment. This suggests that both interventions can be used to help
infertile women combat depression during the waiting period of the result of
fertility treatments (Registration number: IRCT2016020926490N1).
PMID- 29334202
TI - Lifestyle-Related Factors Associated with Reproductive Health in Couples Seeking
Fertility Treatments: Results of A Pilot Study.
AB - Background: The objective of this pilot study was to evaluate the feasibility of
conducting a larger prospective cohort study, which will aim at determining the
independent contribution of male and female lifestyle-related factors to assisted
reproductive technology (ART) success. The study also examined whether couples
seeking fertility treatments present lifestyle-related factors that may interfere
with their reproductive health. MATERIALS AND METHODS: This prospective pilot
study was conducted in a fertility clinic between May 2015 and February 2016.
Feasibility factors evaluated were recruitment rates, compliance with the
protocol, retention rate and ART outcomes at six-month follow-up. Anthropometric
profile and lifestyle habits of both partners were evaluated before the beginning
of infertility treatments. RESULTS: We approached 130 eligible infertile couples.
Among them, 32 (25%) agreed to participate and 28 (88%) complied with the
protocol. At six-month follow-up, seven couples (25%) did not start, or stop,
infertility treatments and 13 couples (62%) achieved a clinical pregnancy. Among
the 28 couples included in the analyses, 16% of the partners were obese and 23%
had abdominal obesity. The majority of the subjects were still drinking alcohol
(84%). Sixty-eight percent of women needed improvement in their diet (vs. 95% of
men, P=0.05) and none of them achieved the Canadian recommendations for physical
activity (vs. 33% of men, P=0.001). Moreover, 35% of the partners had a poor
sleep quality. Overall, women presented a worse reproductive health profile than
men, with 3.1 and 2.4 out of seven adverse factors, respectively (P=0.04).
CONCLUSION: Conducting a large prospective cohort study in our fertility clinic
will be feasible but recruitment and compliance with the protocol need to be
improved. Many women and men seeking fertility treatments present unfavourable
lifestyle-related factors that may explain, at least partially, their
difficulties in conceiving.
PMID- 29334203
TI - Modeling In Vitro Fertilization Data Considering Multiple Outcomes Observed among
Iranian Infertile Women.
AB - Background: Women undergoing in vitro fertilization (IVF) cycles should
successfully go through multiple points during the procedure (i.e., implantation,
clinical pregnancy, no spontaneous abortion and delivery) to achieve live births.
In this study, data from multiple cycles and multiple points during the IVF cycle
are collected for each individual to model the effects of factors associated with
success at different stages of IVF cycles in Iranian infertile women. MATERIALS
AND METHODS: This historical cohort study includes 996 assisted reproductive
technology (ART) cycles of 511 infertile women. Covariates considered in this
study were women's age, type of cycle (fresh or frozen embryo transfer), number
of embryos transferred and having polycystic ovarian syndrome during IVF cycles.
Generalized estimating equations were used for calculation of odds ratio (OR) and
95% confidence intervals (95% CI) of success at different stages during IVF
cycles. Cluster-weighted generalized estimating equations (CWGEE) was also fitted
to handle informative cluster size. RESULTS: After adjusting for potential
confounders, it was seen that receiving frozen embryo transfer was associated
with higher odds of success compared to receiving fresh embryo transfer (adj OR:
2.26, 95% CI: 1.66-3.07); however, cycles with fresh embryo transfer exhibited
better results in clinical pregnancy compared to those receiving frozen embryo.
Being in the age category of 38 to 40 was associated with lower odds of success
compared to the reference category (p<35) in CWGEE model (adj OR: 0.67, 95% CI:
0.45-1.00). The number of embryos transferred was positively associated with the
odds of success in CWGEE (adj OR: 1.21, 95% CI: 1.03-1.42) as well as the GEE
model. CONCLUSION: Receiving frozen embryo was positively associated with odds of
success compared to cycles with fresh embryo. The number of embryos transferred
and women's age were significantly associated with odds of success.
PMID- 29334204
TI - Detection of Chlamydia trachomatis in Pap Smear Samples from South Khorasan
Province of Iran.
AB - Background: Chlamydia trachomatis (CT), the most common bacterial sexually
transmitted infection (STI), leads to pelvic inflammatory disease, infertility
and chronic pelvic pain in women as well as an increased risk of vertical
transmission, conjunctivitis and pneumonitis in infants. It may also be a co
factor along with human papillomavirus (HPV) in cervical cancer progression. We
aimed to determine the prevalence of CT genotypes in genital specimens of women
from South Khorasan, Iran and to test the association between CT and cytology
statistics. MATERIALS AND METHODS: This was a cross-sectional study on 248 Pap
smear samples from women who visited a gynecologist for routine Pap smear testing
in South Khorasan province. Nested polymerase chain reaction (PCR) was used to
test the residual fluids of Pap smears for CT-DNA after cytological examination.
Direct sequencing, alignment and phylogenic analyses were performed on eight
samples to identify their genotypes. RESULTS: The mean age of patients was 37.54
+/- 5.21 years. Most samples had a normal cytology (214 cases, 86.29%). Overall,
31 samples were positive for CT infection (12.5%) of which 20 (9.34%) were normal
and 11 (32.35%) were abnormal, with the frequency difference being significant
(P=0.022). The co-infection of CT/HPV in total was identified in 14 cases (5.6%).
The results of sequencing eight samples out of the 31 CT positive samples
revealed the detection of genotypes D and E, each with four cases. CONCLUSION: We
show that a high prevalence of genital CT infection is present in women with both
normal and abnormal cytology; however, the higher prevalence among women in the
abnormal group may indicate its involvement in cervical neoplasia.
PMID- 29334205
TI - Overexpression of Endometrial Estrogen Receptor-Alpha in The Window of
Implantation in Women with Unexplained Infertility.
AB - Background: Failure in the endometrial receptivity may account for a significant
number of infertility cases including unexplained infertility in women. Reduction
in the endometrial estrogen receptor-alpha (ER-alpha) expression during
implantation may be a critical event that coincides with the expression of
specific genes and the formation of a receptive endometrium. The aim of the
present study was to assess the expression of ER-alpha in the mid-secretory phase
in the endometrium of women with unexplained infertility. MATERIALS AND METHODS:
This case-control study was carried out on randomly selected fertile (n=10) and
infertile (n=16) women whose source of infertility remained unexplained. We
evaluated the expression of ER-alpha and glycodelin- A (GdA) through mRNA level
measurement with real-time polymerase chain reaction (PCR) in the endometrium of
fertile women and patients suffering from unexplained infertility and fertile
women. Endometrial biopsies of each subject were collected during a single
menstrual cycle 7 days after the peak of luteinizing hormone (LH+7). RESULTS:
Endometrial expression level of ER-alpha was significantly (P<0.05) higher in the
patients with unexplained infertility compared to the control. Significantly
(P<0.05) lower levels of GdA expression were seen in women with unexplained
infertility. A statistically non-significant negative correlation was observed
between ER-alpha and GdA mRNA expression. CONCLUSION: Our findings demonstrate
that reduction in the endometrial GdA expression is associated with elevated
expression of ER-alpha in mid-luteal phase. Disruption in the endometrial ER
alpha expression, which leads to defects in uterine receptivity, may contribute
to unexplained infertility.
PMID- 29334206
TI - Decreased Expression of Arginine-Phenylalanine-Amide-Related Peptide-3 Gene in
Dorsomedial Hypothalamic Nucleus of Constant Light Exposure Model of Polycystic
Ovarian Syndrome.
AB - Background: An abnormality in pulse amplitude and frequency of gonadotropin
releasing hormone (GnRH) secretion is the most characteristics of polycystic
ovarian syndrome (PCOS). On the other hand, arginine-phenylalanine-amide
(RFamide)-related peptide-3 (RFRP3) inhibits the secretion of GnRH in mammalian
hypothalamus. The current study performed in order to investigate the expression
of RFRP3 mRNA in the dorsomedial hypothalamic nucleus (DMH) after the induction
of PCOS in a rat model of constant light exposure, and the possible role of
parity on occurrence of PCOS. MATERIALS AND METHODS: In the experimental study,
female nulliparous (n=12) and primiparous (n=12) rats were randomly subdivided
into control and PCOS subgroups (n=6). PCOS were induced by 90 days exposure to
constant light. After 90 days, blood, brain, and ovaries were sampled. Serum
levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and
testosterone were evaluated. In addition, six adult female ovariectomized rats as
a control of real-time polymerase chain reaction (PCR) tests were prepared and in
the DMH of all rats, the relative mRNA expression of RFRP3 was assessed. RESULTS:
Histological evaluation of ovaries represented the polycystic features. In
addition, serum concentrations of testosterone in the PCOS subgroups were more
than the controls (P<0.05). Furthermore, the relative expression of RFRP3 mRNA in
PCOS subgroups was lower than the controls (P<0.05). CONCLUSION: Constant light
model of the PCOS-induced rats decreased the gene expression of RFRP3 in the DMH
that suggests the decrease of RFRP3 may reduce its inhibitory effect on GnRH
during the PCOS pathogenesis. This effect was stronger in the nulliparous rats
than the primiparous.
PMID- 29334207
TI - Screening for Causative Mutations of Major Prolificacy Genes in Iranian Fat
Tailed Sheep.
AB - Background: The presence of different missense mutations in sheep breeds have
shown that the bone morphogenetic protein receptor 1B (BMPR1B), bone
morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) genes
play a vital role in ovulation rate and prolificacy in ewes. Therefore, the
present study aims to investigate BMPR1B, BMP15 and GDF9 gene mutations in
prolific ewes of Iranian fat-tailed Lori-Bakhtiari sheep. MATERIALS AND METHODS:
In the present experimental study, genomic DNA was extracted from whole blood of
10 prolific Lori-Bakhtiari ewes with at least two twinning records in the first
four parities to identify point mutations of the BMPR1B, BMP15 and GDF9 genes,
using DNA sequencing. RESULTS: The results obtained from DNA sequencing showed a
new synonymous mutation (g.66496G>A) in exon 8 of the BMPR1B gene, without any
amino acid change. Sequencing of the BMP15 gene revealed a deletion of 3 bp
(g.656_658delTTC) in exon 1, leading to an amino acid deletion (p.Leu19del). Four
single nucleotide polymorphisms (G1:g.2118G>A, G2:g.3451T>C, G3:g.3457A>G and
G4:g.3701G>A), were detected in exons 1 and 2 of the GDF9 gene, two of which
caused amino acid substitutions (G1: p.87Arg>His and G4: p.241Glu>Lys). These
amino acid alterations are proposed to have a benign impact on structure and
function of the GDF9 polypeptide sequence. CONCLUSION: Three major prolificacy
genes (BMPR1B, BMP15 and GDF9) were polymorphic in Lori-Bakhtiari sheep, although
none of the major causative mutation was detected in this sheep type. Further
studies using high throughput methods such as genome-wide association study
(GWAS) and evaluation of other candidate genes are necessary in the future.
PMID- 29334208
TI - Effects of Crocin on The Pituitary-Gonadal Axis and Hypothalamic Kiss-1 Gene
Expression in Female Wistar Rats.
AB - Background: Saffron (Crocus sativus L.) has been traditionally used as a spice
for coloring and flavoring in some countries cuisine. One of the main components
of saffron is Crocin. Recent research have shown that crocin has various
pharmacological effects. The aim of this study was to assess the effects of
crocin on the Pituitary-Gonadal axis and Kiss-1 gene expression in hypothalamus
and ovarian tissue organization in female Wistar rats. MATERIALS AND METHODS: In
this experimental study, 18 adult female Wistar rats were randomly divided into
three groups. Control group received normal saline and experimental groups
received two different doses of crocin (100 and 200 mg/kg) every two days for 30
days. After the treatment period, blood samples were obtained from the heart and
centrifuged. Next, the serum levels of follicle-stimulating hormone (FSH) and
luteinizing hormone (LH), estrogen and progesterone hormones were measured by
ELISA assay. The ovarian tissues were removed and fixed for histological
investigation. The hypothalamic Kiss-1 gene expression was measured using real
time polymerase chain reaction (PCR). All data were analyzed using one-way ANOVA.
RESULTS: A significant reduction (P=0.038) in the number of atretic graafian
follicles (0.5 +/- 0.31) was observed in rats treated with 200 mg/kg crocin. In
addition, estrogen concentration in experimental groups (35.04 +/- 0.85 and 36.18
+/- 0.69 in crocin 100 and 200 mg/kg groups, respectively) compared to control
group (38.35 +/- 0.64) and progesterone concentration in rats treated with crocin
200 mg/kg (2.06 +/- 0.07) compared to control group (2.16 +/- 0.04),
significantly decreased. Interestingly, relative expressions of Kiss-1 mRNA
significantly decreased in experimental groups (0.00053 +/- 0.00051 and 0.0011 +/
0.00066 in crocin 100 and 200 mg/kg groups, respectively) (P=0.000) compared to
control group (1 +/- 0). CONCLUSION: Crocin, at hypothalamic level, reduces Kiss
1 gene expression and it can prevent follicular atresia and reduce serum levels
of estrogen and progesterone.
PMID- 29334209
TI - Comparison of The Effects of Vitrification on Gene Expression of Mature Mouse
Oocytes Using Cryotop and Open Pulled Straw.
AB - Background: Oocyte cryopreservation is an essential part of the assisted
reproductive technology (ART), which was recently introduced into clinical
practice. This study aimed to evaluate the effects of two vitrification systems
Cryotop and Open Pulled Straw (OPS)-on mature oocytes gene expressions. MATERIALS
AND METHODS: In this experimental study, the survival rate of metaphase II (MII)
mouse oocytes were assessed after cryopreservation by vitrification via i. OPS or
ii. Cryotop. Then we compared the fertilization rate of oocytes produced via
these two methods. In the second experiment, we determined the effects of the two
vitrification methods on the expression of Hspa1a, mn-Sod, and beta-actin genes
in vitrified-warmed oocytes. Denuded MII oocytes were vitrified in two
concentrations of vitrification solution (VS1 and VS2) by Cryotop and straw. We
then compared the results using the two vitrification methods with fresh control
oocytes. RESULTS: mn-Sod expression increased in the vitrified-warmed group both
in OPS and Cryotop compared with the controls. We only detected Hspa1a in VS1 and
control groups using Cryotop. The survival rate of the oocytes was 91.2% (VS1)
and 89.2% (VS2) in the Cryotop groups (P=0.902) and 85.5% (VS1) and 83.6% (VS2)
in the OPS groups (P=0.905). There were no significant differences between the
Cryotop and the OPS groups (P=0.927). The survival rate in the Cryotop or the OPS
groups was, nevertheless, significantly lower than the control group (P<0.001).
The fertilization rates of the oocytes were 39% (VS1) and 34% (VS2) in the
Cryotop groups (P=0.902) and 29 %( VS1) and 19.7% (VS2) in the OPS groups
(P=0.413). The fertilization rates were achieved without significant differences
among the Cryotop and OPS groups (P=0.755). CONCLUSION: Our results indicated
that Cryotop vitrification increases both cooling and warming rates, but both
Cryotop and OPS techniques have the same effect on the mouse oocytes after
vitrification.
PMID- 29334210
TI - Combined Effect of Retinoic Acid and Basic Fibroblast Growth Factor on Maturation
of Mouse Oocyte and Subsequent Fertilization and Development.
AB - Background: In this experimental study, germinal vesicle (GV) oocytes obtained
from two-months-old NMRI mice were randomly divided into control, sham and three
experimental groups. The basic culture medium was alpha-MEM supplemented with 10%
fetal bovine serum (FBS), 50 mg/l streptomycin, 60 mg/l penicillin and 10 ng/ ml
epidermal growth factors. Each of the experimental groups received one of the
following treatments: RA (2 MUM), bFGF (20 ng/ml) or combination of RA and bFGF
with the indicated concentrations. After 24 hours, capacitated spermatozoa were
added to in vitro matured oocytes. Five hours later, the oocytes were cultured in
fresh droplets of M2 medium for 24 hours and assessed for cleavage to the two
cells stage. MATERIALS AND METHODS: In this experimental study, germinal vesicle
(GV) oocytes obtained from two-months-old NMRI mice were randomly divided into
control, sham and three experimental groups. The basic culture medium was alpha
MEM supplemented with 10% fetal bovine serum (FBS), 50 mg/l streptomycin, 60 mg/l
penicillin and 10 ng/ ml epidermal growth factors. Each of the experimental
groups received one of the following treatments: RA (2 MUM), bFGF (20 ng/ml) or
combination of RA and bFGF with the indicated concentrations. After 24 hours,
capacitated spermatozoa were added to in vitro matured oocytes. Five hours later,
the oocytes were cultured in fresh droplets of M2 medium for 24 hours and
assessed for cleavage to the two-cells stage. RESULTS: As compared with the
control group, the rate of maturation was significantly increased in the RA
(P<0.001) and bFGF+RA (P<0.02) groups with 58 +/- 10 and 57 +/- 3.46,
respectively. The rate of maturation was significant in the RA (P<0.02) and
bFGF+RA (P<0.03) groups, in comparison with the bFGF group. The bFGF+RA group had
higher rate (83 +/- 1.52) of two-cells development, than control (33 +/- 1,
P<0.001). CONCLUSION: Our findings showed beneficial effects of 2 MUM RA and 20
ng/ml bFGF combination on mouse oocyte IVM.
PMID- 29334211
TI - Curcumin and Quercetin Ameliorated Cypermethrin and Deltamethrin-Induced
Reproductive System Impairment in Male Wistar Rats by Upregulating The Activity
of Pituitary-Gonadal Hormones and Steroidogenic Enzymes.
AB - Background: Dietary antioxidants protect tissues and organs against
insecticides/xenobiotic-induced damage. In the present study, we evaluated the
results of exposure to synthetic pyrethroid insecticides, cypermethrin (Cyp) and
deltamethrin (Del) and possible protective effects of curcumin and quercetin on
reproductive system in male Wistar rats. MATERIALS AND METHODS: In this
controlled experimental study, 42 male Wistar rats were randomly divided into 7
groups of 6 animals. Group A served as control, group B was exposed to Cyp (2
mg/kg.bw), group C was exposed to Del (2 mg/kg.bw), group D was exposed to
Cyp+Del (2 mg/kg.bw each), group E was exposed to Cyp+Del and treated with
curcumin (100 mg/kg.bw), group F was exposed to Cyp+Del and treated with
quercetin (100 mg/kg.bw) and group G was exposed to Cyp+Del and treated with
quercetin+curcumin for 45 days. RESULTS: Exposure to Cyp and Del caused decreases
in reproductive organs weight, sperm count, sperm motility, level of sex hormones
viz. testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone
(LH), steroidogenic enzymes viz. 3beta-hydroxyl steroid dehydrogenase (3beta-HSD)
and 17beta-HSD, non-enzymatic antioxidant glutathione (GSH) and enzymatic
antioxidants viz. superoxide dismutase (SOD), catalase (CAT), glutathione
peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR)
activity and increases in sperm abnormalities and lipid peroxidation (LPO). The
exposure also adversely affected the histo-achitecture of testes. Single and
combined treatment with curcumin and quercetin significantly ameliorated Cyp and
Del-induced damage in reproductive system. CONCLUSION: Curcumin and quercetin
protected against Cyp and Del-induced reproductive system toxicity and oxidative
damage in rats. The increases in activities of 3beta-HSD and 17beta-HSD with
concomitant increases in testosterone were mainly responsible for ameliorating
effects of curcumin and quercetin. Curcumin showed slightly better activity as
compared to quercetin. The combination of both antioxidants offered more
protection compared to each one alone.
PMID- 29334212
TI - Comparison of The Efficacy and Safety of Palomo, Ivanissevich and Laparoscopic
Varicocelectomy in Iranian Infertile Men with Palpable Varicocele.
AB - Background: This study aimed to compare the effects of three commonly used
varicocelectomy techniques namely, open retroperitoneal ligation (Palomo), open
inguinal ligation (Ivanissevich) and laparoscopy, in Iranian infertile men.
MATERIALS AND METHODS: This retrospective study was conducted on 70 infertile men
with palpable varicocele who underwent one of the varicocelectomy techniques
namely, Palomo, Ivanissevich, or laparoscopy. Basic information about semen
parameters were collected and registered prior to the surgery. Three months after
the surgery, semen parameters and surgical complications were investigated in all
patients. RESULTS: The Palomo technique was significantly associated with fewer
complications compared to other techniques (P=0.006). The means of sperm
concentration, normal motility and normal morphology were significantly different
among the three groups after surgery (P=0.025, 0.023 and 0.047, respectively).
However, after adjustment for potential confounders, in addition to the baseline
values of semen parameters, significant differences were observed only in sperm
concentration among the groups (P=0.040). CONCLUSION: Varicocelectomy improved
sperm parameters. The Ivanissevich technique was more effective in improving
sperm concentration compared to the laparoscopic method. The lowest rates of
complications were related to the Palomo technique.
PMID- 29334213
TI - Conservative Management of Ovarian Fibroma in A Case of Gorlin-Goltz Syndrome
Comorbid with Endometriosis.
AB - Ovarian fibromas are the most common benign solid ovarian tumors, which are often
difficult to diagnose preoperatively. Ovarian fibromas, especially in bilateral
cases, may be cases of Gorlin-Goltz syndrome (GGS), a rare autosomal dominant
disorder with predisposition to basal cell carcinomas (BCCs) and other various
benign and malignant tumors. This case report describes a 25 year-old female with
GGS, bilateral ovarian fibroma, endometriosis and septated uterus, which was
referred to the Gynecology Clinic of Rasoul-e-Akram Hospital in October 2016.
This patient had facial asymmetry due to recurrent odontogenic keratocysts. In
young cases of ovarian fibromas as reported here, conservative surgical
management can preserve ovarian function and fertility. These patients must be
followed up by a multidisciplinary team and submitted to periodic tests.
PMID- 29334214
TI - Quality of Life and Its Influencing Factors of Couples Referred to An Infertility
Center in Shiraz, Iran.
AB - In this article which was published in Int J Fertil Steril, Vol 11, No 4, Jan-Mar
2018, on pages 293-297, the "Duration of tducation (male)" was misspelled in
Table 1. The corrected one is "Duration of education (male)". In the sentence
"These differences might be related to the use of a fertility-specific instrument
(FertiQoL) in the study by Huppelschoten et al. (23) and the current study
compared to the general QoL assessment instrument by Chachamovich et al. (24) and
Rashidi et al. (15)." Which was at the page of 296 in the discussion section, the
word "generic" was corrected in to "general".
PMID- 29334215
TI - A year in review in Minerva Anestesiologica 2017 Critical Care: experimental and
clinical studies.
PMID- 29334216
TI - Lysosome-Independent Intracellular Drug/Gene Codelivery by Lipoprotein-Derived
Nanovector for Synergistic Apoptosis-Inducing Cancer-Targeted Therapy.
AB - In this paper, reconstituted high-density lipoprotein (rHDL), a lipoprotein
derived nanovector, was constructed for codelivery of paclitaxel (PTX) and wild
type p53 gene (p53). The particle size and the zeta potential of PTX-DODAB/p53
rHDL nanoparticles were 177.2 nm and -20.06 mV, respectively. Meanwhile, they
exhibited great serum stability and satisfactory sustained release
characteristics in vitro. PTX-DODAB/pDNA-rHDL nanoparticles simultaneously
improved the cellular uptake of PTX and pDNA via scavenger receptor B type I (SR
BI) mediated lysosome-independent internalization and promoted the transfection
of pDNA in MCF-7 cells, which were revealed by flow cytometry and confocal laser
scanning microscopy analyses. The high p53 protein expression in MCF-7 cells
after rHDL-mediated transfection was detected by Western blotting assay.
Moreover, PTX-DODAB/p53-rHDL nanoparticles showed superior cytotoxicity and
significantly induced apoptosis in SR-BI overexpressed MCF-7 cells. In in vivo
studies, PTX-DODAB/p53-rHDL nanoparticles without obvious toxic effects to
vessels, blood, or major organs exhibited efficient tumor targeting and
encouraging antitumor effects on tumor-bearing nude mice compared with controls.
All the results above indicated that PTX-DODAB/p53-rHDL nanoparticles held broad
prospects in combination of chemotherapeutics and gene therapeutic agents for
cancer-targeted therapy.
PMID- 29334218
TI - Photochemically Induced Intramolecular Radical Cyclization Reactions with Imines.
AB - The photochemically induced intramolecular hydrogen abstraction or hydrogen atom
transfer in cyclic imines 8a,b followed by a cyclization is investigated. Two
types of products are observed, one resulting from the formation of a C-C bond,
the other from the formation of a C-N bond. A computational study reveals that
hydrogen is exclusively transferred to the imine nitrogen leading to a triplet
diradical intermediate. After intersystem crossing, the resulting zwitterionic
intermediate undergoes cyclization leading to the final product.
PMID- 29334217
TI - Characterization of an Hsp90-Independent Interaction between Co-Chaperone p23 and
Transcription Factor p53.
AB - Cancer-suppressing transcription factor p53 is regulated by a wide variety of
cellular factors, including many chaperones. The DNA-binding domain (DBD) of p53
is known to interact with the chaperone Hsp90, but the role of other members of
the chaperone network, including co-chaperones such as p23, is unknown. Using a
combination of nuclear magnetic resonance (NMR) titration, isothermal titration
calorimetry, fluorescence anisotropy, and native agarose gel electrophoresis, we
have identified a direct interaction between the p53 DBD and Hsp90 co-chaperone
p23 that occurs in the absence of Hsp90. The affinity is relatively weak and
largely determined by electrostatic interactions between the acidic C-terminal
disordered tail of p23 and the two DNA-binding regions of the p53 DBD. We show by
NMR and native agarose gel electrophoresis that a p53-specific double-stranded
DNA sequence competes successfully with p23 for binding to the p53 DBD. The Hsp90
independence of the interaction between p23 and p53 DBD, together with the
competition of p23 versus DNA for p53, raises the intriguing possibility that
p23, like other small charged proteins, may affect p53 in hitherto unknown ways.
PMID- 29334219
TI - Mussel-Inspired Conductive Polymer Binder for Si-Alloy Anode in Lithium-Ion
Batteries.
AB - The excessive volume changes during cell cycling of Si-based anode in lithium ion
batteries impeded its application. One major reason for the cell failure is
particle isolation during volume shrinkage in delithiation process, which makes
strong adhesion between polymer binder and anode active material particles a
highly desirable property. Here, a biomimetic side-chain conductive polymer
incorporating catechol, a key adhesive component of the mussel holdfast protein,
was synthesized. Atomic force microscopy-based single-molecule force measurements
of mussel-inspired conductive polymer binder contacting a silica surface revealed
a similar adhesion toward substrate when compared with an effective Si anode
binder, homo-poly(acrylic acid), with the added benefit of being electronically
conductive. Electrochemical experiments showed a very stable cycling of Si-alloy
anodes realized via this biomimetic conducting polymer binder, leading to a high
loading Si anode with a good rate performance. We attribute the ability of the Si
based anode to tolerate the volume changes during cycling to the excellent
mechanical integrity afforded by the strong interfacial adhesion of the
biomimetic conducting polymer.
PMID- 29334220
TI - Computational Design, Synthesis, and Structure Property Evaluation of 1,3
Thiazole-Based Color-Tunable Multi-heterocyclic Small Organic Fluorophores as
Multifunctional Molecular Materials.
AB - Probing the chemical space of luminescent organic materials built on novel cores
is highly imperative for its potential to expand the horizons of advanced
functional materials. Small organic fluorophores possessing therapeutic traits
can contribute to theranostics. We coupled computational and classical synthetic
chemistry strategies for the rational design of 5-(hetero-2-yl)-1,3-thiazoles as
color-tunable fluorophore core. With the aid of DFT and TD-DFT, we prove that the
multi-heterocyclic system is built on a thiazole-het core with three inherent
tunable sites on thiazole (C2, C4, and C5) capable of accommodating a panoply of
substituents as a multifunctional molecular materials' platform. This de novo
design offered unprecedented freedom to control strength and direction of charge
transfer by varying donor-acceptor fragments. A 30-member fluorophore library
built on thiazole-thiophene/furan core was accomplished using commercial reagents
by a simple [4 + 1] synthesis. Structure-photophysical property studies revealed
large Stokes shift, positive solvatochromism, acidochromism, and color tunability
in different solvents and were rationalized using computational calculations. In
vitro studies indicated 1a to be active against HL-60 cell lines, suggesting the
possibility of expanding the core for theranostics. The lower values of computed
hole reorganization energies indicated their potential as hole transporting
materials in optoelectronics and widen the scope of these molecules as advanced
functional materials.
PMID- 29334222
TI - Online Preconcentration in Capillaries by Multiple Large-Volume Sample Stacking:
An Alternative to Immunoassays for Quantification of Amyloid Beta Peptides
Biomarkers in Cerebrospinal Fluid.
AB - A novel electrokinetic preconcentration approach, so-called multiple pressure
assisted large-volume sample stacking with an electroosmotic flow pump (M-PA
LVSEP), was developed to allow in-capillary enrichment and separation of analytes
from unlimited sample volumes. With this approach, the inherent limitation of in
capillary electrokinetic preconcentrations to the separation capillary volume can
be overcome. The M-PA-LVSEP protocol relies on repeated cycles of pressure
assisted electroosmotic pumping and injection of extremely large sample volumes
for analyte stacking and sample matrix removal. This technique was developed to
address the challenge of sensitive and simultaneous determination of several
amyloid beta (Abeta) peptides, which are biomarkers for the molecular diagnosis
of Alzheimer's disease (AD). For the first time, reliable quantification of
different species of fluorescently derivatized Abeta peptides, that is, Abeta 1
42, Abeta 1-40, and Abeta 1-38 down to subnanomolar ranges in cerebrospinal
fluids (CSF) from AD and non-demented patients (healthy controls) was made
possible without recourse to immunoassay, immunoprecipitation, or mass
spectrometry approaches. Based on the stacking from a sample plug representing up
to 400% of the total capillary volume, sensitive enhancement factors up to 170
could be achieved with this "antibody free" approach. Quantification limits for
these Abeta peptides down to 0.05 nM with capillary electrophoresis coupled with
laser-induced fluorescent detection could be obtained. Excellent agreement
between results from M-PA-LVSEP and the gold standard ELISA method was achieved
for measurements of Abeta 1-42 in CSF, with a determination correlation (r2)
better than 0.993.
PMID- 29334221
TI - Extracellular Enzyme Composition and Functional Characteristics of Aspergillus
niger An-76 Induced by Food Processing Byproducts and Based on Integrated
Functional Omics.
AB - Byproducts of food processing can be utilized for the production of high-value
added enzyme cocktails. In this study, we utilized integrated functional omics
technology to analyze composition and functional characteristics of extracellular
enzymes produced by Aspergillus niger grown on food processing byproducts. The
results showed that oligosaccharides constituted by arabinose, xylose, and
glucose in wheat bran were able to efficiently induce the production of
extracellular enzymes of A. niger. Compared with other substrates, wheat bran was
more effective at inducing the secretion of beta-glucosidases from GH1 and GH3
families, as well as >50% of proteases from A1-family aspartic proteases.
Compared with proteins induced by single wheat bran or soybean dregs, the protein
yield induced by their mixture was doubled, and the time required to reach peak
enzyme activity was shortened by 25%. This study provided a technical platform
for the complex formulation of various substrates and functional analysis of
extracellular enzymes.
PMID- 29334223
TI - A Novel Color Modulation Analysis Strategy through Tunable Multiband Laser for
Nanoparticle Identification and Evaluation.
AB - Creating color difference and improving the color resolution in digital imaging
is crucial for better application of color analysis. Herein, a novel color
modulation analysis strategy was developed by using a homemade tunable multiband
laser illumination device, in which the portions of R, G, and B components of the
illumination light are discretionarily adjustable, and hence the sample color
could be visually modulated continuously in the RGB color space. Through this
strategy, the color appearance of single gold nanorods (AuNRs) under dark-field
microscopy was migrated from the spectrally insensitive red region to the
spectrally sensitive green-yellow region. Unlike the traditional continuous-wave
light source illumination, wherein the small spectral variations in the samples
within a narrow spectral range are averaged by the whole spectrum of the light
source, leading to little color difference, the application of sharp, multiband
laser illumination could enlarge the color separation between samples, thus
resulting in high spectral sensitivity in color analysis. By comparing the
corresponding color evolution processes of different samples as the multiband
combination of the laser illumination was changed, more efficient color
separation of AuNRs was achieved. With this instrument and single Ag@AuNRs as the
sulfide probe, we achieved high throughput and highly sensitive detection of
sulfide at a detection limit of 0.1 nM, a more than 2 orders of magnitude
improvement compared to the previous color sensing scheme. This strategy could be
utilized for nanoparticle identification, evaluation, and determination in
biological imaging and biochemical analysis.
PMID- 29334224
TI - Diversity-Oriented Approach to N-Heterocyclic Compounds from alpha-Phenyl-beta
enamino Ester via a Mitsunobu-Michael Reaction Sequence.
AB - Herein we delineate a novel route for the diastereoselective construction of
diversely substituted N-heterocyclic ring systems as valuable scaffolds for
natural products and pharmaceuticals, starting from an easily accessible
prochiral alpha-phenyl-beta-enamino ester. The reaction sequence relies on the
unexplored reactivity of alpha-phenyl-beta-enamino ester as a nucleophilic
partner in the Mitsunobu reaction to forge the N-tethered alkene
alcohol/thiol/amine intermediate, which was subjected to an intramolecular hetero
Michael addition reaction under mild conditions to furnish the respective N
heterocyclic compounds embedded with an exocyclic chiral center in high yields
and excellent diastereoselectivities. The methodology is amenable for a broad
range of substrates based on a metal-free approach.
PMID- 29334225
TI - Fate of Poly(3-octylthiophene) Transducer in Solid Contact Ion-Selective
Electrodes.
AB - An experimental approach allowing visualization and quantification of the
underestimated spontaneous process of partition of conducting polymer transducer
material to the ion-selective membrane phase is proposed. The approach proposed
is based on optical properties of the transducer material applied, using
polythiophene as a model system. It is shown that this process occurs not only
during the sensor preparation step but also during pretreatment of the sensor
before use. As shown, this uncontrolled partition of the transducer to the
receptor leads to conducting polymer contents in the membrane phase reaching 0.5%
w/w; this process is accompanied by a partial spontaneous change of the oxidation
state of polythiophene. The conducting polymer present in the membrane
participates to some extent in the overall response of the sensor, which can be
observed as a change in the polythiophene optical emission spectra. Fluorescence
microscopic images obtained clearly show that the conducting polymer is
distributed throughout the membrane thickness, being present also at the
membrane/solution interface. The experimental results presented were obtained for
K+-selective sensors using poly(3-octylthiophene) as a model transducer; however,
the proposed approach is also applicable for other systems.
PMID- 29334226
TI - Ethnic youth and sexual identity: the role of clinical and social support for
'double minorities'.
AB - OBJECTIVES: Sexual-minority youth exhibit increased rates of psychiatric
morbidity, subject to various social factors. We examine the impact of ethnicity
and culture on these phenomena, with particular reference to Asian youth living
in Western societies. CONCLUSIONS: Youth from minority ethnic groups who do not
identify with their native gender and/or who are not exclusively heterosexual are
known as 'double minorities'. Available evidence suggests that such individuals
are at particularly increased risk of depression and suicide, but that this may
be mitigated by social support. More research is needed to understand the
challenges faced by 'double minorities', notably their perception of and ability
to access available clinical and social supports.
PMID- 29334227
TI - Using a television documentary to prevent suicide in men and boys.
AB - OBJECTIVES: We investigated whether a documentary about masculinity and
suicidality ( Man Up) could raise males' awareness of societal pressures to
conform to masculine norms and influence their likelihood of connecting with
their male friends and seeking help. METHODS: We conducted a repeat cross
sectional survey, posting versions of the survey online before and after Man Up
was screened. RESULTS: 1287 male respondents completed the survey; 476 completed
the pre-screening survey, 811 the post-screening survey (192 had not viewed Man
Up, 619 had). Those who had viewed Man Up were more likely to desire closer
relationships with their male friends than those who had not, and had greater
awareness of societal pressures on males, but were no more likely to seek help.
Almost all respondents who saw Man Up indicated they would recommend it to
others, and most said it changed the way they thought about the term 'man up'.
They indicated they would be likely to undertake a number of adaptive actions
following the show, and provided overwhelmingly positive feedback. CONCLUSIONS:
Man Up appeared to effectively address factors that place males at heightened
risk of suicide.
PMID- 29334228
TI - Use of ECT in the presence of acute bilateral posterior vitreous detachmanet.
AB - OBJECTIVES: We describe a case of acute bilateral posterior vitreous detachment
(PVD) in a 71-year-old female, which developed during a course of
electroconvulsive therapy (ECT) for treatment-resistant depression. The risks and
benefits of continuing ECT were assessed and the patient completed the full
course of 16 ECT treatments without further ophthalmic complications.
CONCLUSIONS: As the incidence of PVD increases with age, and ECT is used more
frequently in elderly people with depression, we recommend paying attention to
ophthalmic symptoms as part of the routine clinical monitoring of ECT side
effects. If ophthalmic symptoms occur, the risks and benefits of ECT need to be
weighed up including consultation with an ophthalmologist.
PMID- 29334229
TI - Physical and psychological health of carers of young people with first episode
psychosis.
AB - OBJECTIVE: Carers of people with psychosis may experience psychological distress
and caregiving burden. However, few studies have examined both psychological and
physical health of carers of young people with first episode psychosis (FEP).
METHOD: A total of 32 young people with FEP and 42 of their carers were recruited
from a mental health service. Standardised scales were administered to assess
carers' psychological distress and risk for development of Type 2 diabetes. Their
body mass index, waist circumference and blood pressure were measured. RESULTS: A
total of 24% ( n = 10) of carers experienced high/very high psychological
distress and 39.0% ( n = 16) had high risk for Type 2 diabetes. It was common for
carers to be overweight ( n = 33, 78.6%) and to have hypertension ( n = 14,
33.3%). Carers' higher levels of psychological distress were associated with
shorter duration of illness in the young person. CONCLUSIONS: Caring for a young
person with FEP is associated with poor physical and psychological health.
Findings show the importance of supporting carers' physical and psychological
health early in treatment of young people with FEP.
PMID- 29334230
TI - DNA methylation changes and evolution of RNA-based duplication in Sus scrofa:
based on a two-step strategy.
AB - AIM: This study aims to couple DNA methylation changes and evolution of
retrogenes. MATERIALS & METHODS: A new two-step strategy was developed to screen
retrogenes. Further, reduced representation bisulfite sequencing and RNA-seq data
of eight tissues were used to analyze retrogenes. RESULTS: A total of 964
retrocopies were identified and new retrocopies were available for the synthesis
of glycans and lipids corresponding to pig phenotypic traits. Retrogenes were
consistently hypermethylated. Hypomethylation of parental genes presented more
susceptibility to retroposition. Promoter DNA methylation of retrogenes was
negatively correlated with evolutionary time and played important roles in
regulating retrogene tissue-specific expression pattern. CONCLUSION: A two-step
procedure is effective and necessary for identifying retrogenes. DNA methylation
drives origination, survival, evolution and expression of retrogenes.
PMID- 29334231
TI - Social capital and PTSD among PLWHA in China: the mediating role of resilience
and internalized stigma.
AB - Post-traumatic Stress Disorder (PTSD) is frequent among people living with
HIV/AIDS (PLWHA). Few studies have investigated social-psychological predictors
of PTSD in China. This study aimed to examine relationships between social
capital, stigma, resilience and PTSD among PLWHA in China, and to provide
effective suggestions for PTSD intervention. A cross-sectional study of 520 PLWHA
was conducted from November 2015 to January 2016. Survey data were collected
using anonymous self-reported questionnaire. Multivariable analyses were used to
examine related factors of PTSD, and causal mediation analyses were conducted to
assess whether stigma and resilience were mediators. Results indicated that
higher risk of PTSD was independent associated with stronger stigma, decreasing
social capital and lower resilience. There was an indirect relationship of social
capital on PTSD mediated through resilience and HIV-related stigma. Therefore,
PTSD intervention programs should not only pay attention to the role of social
capital on PTSD, but also attach importance to stigma and resilience on PTSD
symptoms.
PMID- 29334232
TI - Stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma: imaging
evaluation post treatment.
AB - Surgical resection, when feasible, is the standard of care for hepatocellular
carcinoma. However, many tumours are not resectable at the time of diagnosis.
Recently, stereotactic body radiation therapy (SBRT) has emerged as a non
invasive local therapy for both non-resectable primary hepatic malignancies as
well as hepatic metastases. Knowledge of the expected hepatic parenchymal
appearance post treatment, as well as potential pitfalls and complications, is
essential for accurate evaluation of treatment response. This pictorial review
provides a fundamental description of the SBRT technique, outlines the expected
cross-sectional imaging appearances of tumour response, and highlights potential
pitfalls in interpretation. The expected liver parenchymal changes post-SBRT are
also reviewed, along with some common radiation-induced complications.
PMID- 29334233
TI - Perceived discrimination and mental health among older African Americans: the
role of psychological well-being.
AB - OBJECTIVES: Examine the effect of perceived discrimination (both racial and non
racial) on the mental health of older African Americans and explore the buffering
role of psychological well-being (purpose in life and self-acceptance). METHODS:
Using an older African American subsample from the National Health Measurement
Study (n = 397), multiple regression model by gender was used to estimate the
effects of two types of discrimination (every day and lifetime) on SF-36 mental
component and mediating role of two concepts of psychological well-being.
RESULTS: With no gender difference on the everyday discrimination, older men
experienced more lifetime discrimination than older women. The older men's model
found that the depressive symptomology was significantly explained by only
everyday discrimination and mediated by self-acceptance. The older women's model
was significant, with everyday discrimination and both self-acceptance and
purpose in life emerging as mediating variables. DISCUSSION: The prevalence of
institutional lifetime discrimination for older African American men is
consistent with previous research. Inconsistency with past research indicated
that only everyday discrimination is statistically associated with depressive
symptoms. Considering the buffering role of psychological well-being served for
mental health problems, practitioners need to emphasize these factors when
providing services to older African Americans. Equally important, they must
address racial discrimination in mental health care settings.
PMID- 29334234
TI - Is there an association between severity of illness and psychiatric symptoms in
patients with chronic renal failure?
AB - Chronic renal failure (CRF) is a frequent condition in elderly subjects, and it
is associated with psychiatric comorbidity, especially depressive symptoms.
Purpose of the present research was to compare patients with different severity
of chronic kidney disease (CKD) in terms of psychiatric symptoms. One hundred CKD
subjects were randomly selected among those attending the Department of
Nephrology, University of Milan. The patients were evaluated through the
following rating scales: Mini-Mental State Examination (MMSE), Beck Depression
Inventory (BDI), Symptom Checklist (SCL-90), Kidney Disease Quality of Life-
Short Form (KDQOL-SF) and Cumulative Illness Rating Scale (CIRS). A multivariable
linear regression analysis was performed considering eGFR as continuous-dependent
variable and rating scale scores as independent variables. A worse eGFR
significantly correlated with the score about the effects of kidney disease on
daily life (r = 0.25, p = 0.01) and the burden of kidney disease (r = 0.18, p =
0.05). Statistical significance of kidney disease on daily life persisted also in
the final multivariate model (t = 2.04, p = 0.04). Severity of renal dysfunction
seems to influence few psychiatric outcomes, particularly those related to
quality of life and daily functioning. This result might depend on the over
worrying derived from the necessity to start a renal replacement therapy in the
near future.
PMID- 29334235
TI - Impact of an assertive community treatment model of care on the treatment of
prisoners with a serious mental illness.
AB - OBJECTIVES: This study aims to describe the impact of a mental health assertive
community treatment prison model of care (PMOC) on improving the ability to
identify prisoner needs, provide interventions and monitor their efficacy.
METHODS: We carried out a file review across five prisons of referrals in the
year before the implementation of the PMOC in 2010 ( n = 423) compared with
referrals in the year after ( n = 477). RESULTS: Some improvements in the
identification of needs and providing interventions were detected. There was
increased use of medication management and clinically significant improvement in
addressing engagement with families. Monthly multi-disciplinary team face-to-face
contact improved. CONCLUSIONS: Meeting the needs of mentally ill prisoners is
challenged by the complexity of the custodial environment. Improvements made
resulted from changing the model of care, rather than adding new resources.
PMID- 29334236
TI - Whole Body MRI and oncology: recent major advances.
AB - MRI is a very attractive approach for tumour detection and oncological staging
with its absence of ionizing radiation, high soft tissue contrast and spatial
resolution. Less than 10 years ago the use of Whole Body MRI (WB-MRI) protocols
was uncommon due to many limitations, such as the forbidding acquisition times
and limited availability. This decade has marked substantial progress in WB-MRI
protocols. This very promising technique is rapidly arising from the research
world and is becoming a commonly used examination for tumour detection due to
recent technological developments and validation of WB-MRI by multiple studies
and consensus papers. As a result, WB-MRI is progressively proposed by
radiologists as an efficient examination for an expanding range of indications.
As the spectrum of its uses becomes wider, radiologists will soon be confronted
with the challenges of this technique and be urged to be trained in order to
accurately read and report these examinations. The aim of this review is to
summarize the validated indications of WB-MRI and present an overview of its most
recent advances. This paper will briefly discuss how this examination is
performed and which are the recommended sequences along with the future
perspectives in the field.
PMID- 29334237
TI - Safety of working patterns among UK neuroradiologists: what can we learn from the
aviation industry and cognitive science?
AB - As the volume and complexity of imaging in the UK continues to rise, there is
pressure on radiologists to spend increasing lengths of time reporting to cope
with the growing workload. However, there is limited guidance for radiologists
about structuring the working day to strike the necessary balance between
achieving satisfactory reporting volume and maintaining quality and safety. We
surveyed 86 neuroradiologists (receiving 59 responses), regarding time spent
reporting, frequency and duration of work breaks, and break activities. Our
results demonstrate that some neuroradiologists report for up to 12 h a day and
for 4 h before taking a break. Mean duration of breaks is less than 15 min and
these often consist of computer screen-based or cognitively demanding tasks. Many
areas of medicine have looked to the aviation industry to develop improvements in
safety through regulated, standardised practices. There are parallels between the
work of air traffic controllers (ATCs) and radiologists. We review the
legislation that controls the working hours of UK ATCs to minimise fatigue
related errors, and its scientific basis. We also consider the vigilance
decrement, a concept in cognitive science which describes the reduction in
performance with increasing time-on-task. We conclude that, in comparison with
ATCs, work patterns among radiologists are poorly standardised and potentially
dangerous. Evidence suggests that placing limits on reporting time and minimum
break duration, as well as ensuring appropriate break activities, can benefit
reporting quality. It is imperative that radiologists and managers heed these
lessons, to improve standards and protect patients from error.
PMID- 29334238
TI - Chemical constituents from the flowers of Satsuma mandarin and their free radical
scavenging and alpha-glucosidase inhibitory activities.
AB - Flowers of Citrus plants are used as mild sedatives and for the treatment of
insomnia in traditional medicines. In Japan, tea made from the flowers of Satsuma
mandarin is consumed as healthy drink. Hesperidin (1), hesperetin (2), rutin (3),
quercetin (4), nicotiflorin (5), eriocitrin (6), narirutin (7), phenylethyl
glucoside (8) and unshuoside A (9) were isolated from the MeOH extract of fresh
flowers. Structure elucidation of these compounds was performed on the basis of
NMR spectroscopic data. Among them, rutin (3), quercetin (4) and eriocitrin (6)
showed potent free radical scavenging activity, whereas hesperetin (2) and
quercetin (4) showed potent alpha-glucosidase inhibitory activity.
PMID- 29334239
TI - Antimicrobial and antiquorum-sensing activity of Ricinus communis extracts and
ricinine derivatives.
AB - Ricinine (1), a known major alkaloid in Ricinus communis plant, was used as a
starting compound for the synthesis of six ricinine derivatives; two new and four
known compounds. The new derivatives; 3-amino-5-methyl-1H-pyrazolo[4,3-c]pyridin
4(5H)-one (2), and 3-amino-5-methyl-1-(phenylsulfonyl)-1H-pyrazolo[4,3-c]pyridin
4(5H)-one (3), as well as the previously prepared derivatives (4-7) were
subjected for antimicrobial and antiquorum-sensing evaluation in comparison to
different R. communis extracts. Acetyl ricininic acid derivative (5) showed the
highest antimicrobial activity among all tested derivatives against
Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas
aeuroginosa and Candida albicans. However, compound 7 (4-methoxy-1-methyl-2-oxo
1,2-dihydropyridine-3-carboxamide) showed the highest antiquorum-sensing activity
among all tested compounds and extracts. These findings proved the usefulness of
ricinine as a good scaffold for the synthesis of new antimicrobial and antiquorum
sensing derivatives in spite of its poor contribution to the antimicrobial
activity of the plant extracts.
PMID- 29334240
TI - New method for estimating arterial pulse wave velocity at single site.
AB - The clinical importance of measuring local pulse wave velocity (PWV), has
encouraged researchers to develop several local methods to estimate it. In this
work, we proposed a new method, the sum-of-squares method [Formula: see text],
that allows the estimations of PWV by using simultaneous measurements of blood
pressure (P) and arterial diameter (D) at single-location. Pulse waveforms
generated by: (1) two-dimensional (2D) fluid-structure interaction simulation
(FSI) in a compliant tube, (2) one-dimensional (1D) model of 55 larger human
systemic arteries and (3) experimental data were used to validate the new formula
and evaluate several classical methods. The performance of the proposed method
was assessed by comparing its results to theoretical PWV calculated from the
parameters of the model and/or to PWV estimated by several classical methods. It
was found that values of PWV obtained by the developed method [Formula: see text]
are in good agreement with theoretical ones and with those calculated by PA-loop
and D2P-loop. The difference between the PWV calculated by [Formula: see text]
and PA-loop does not exceed 1% when data from simulations are used, 3% when in
vitro data are used and 5% when in vivo data are used. In addition, this study
suggests that estimated PWV from arterial pressure and diameter waveforms provide
correct values while methods that require flow rate (Q) and velocity (U)
overestimate or underestimate PWV.
PMID- 29334241
TI - Transcriptional regulation on the gene expression signature in combined allergic
rhinitis and asthma syndrome.
AB - AIM: This study was intended to evaluate transcriptional regulation of gene
expression signatures in combined allergic rhinitis and asthma syndrome (CARAS).
MATERIALS & METHODS: The blood samples of three patients with CARAS, three
patients with allergic rhinitis and three normal controls were obtained. The
cuffdiff, miRDeep2 and DEGseq were used to quantify the expression of genes and
miRNAs, respectively. And p-value < 0.01 and false discovery rate < 0.001 were
considered as significant differences of genes and miRNAs, respectively. Gene
ontology and the Kyoto Encyclopedia of Genes and Genomes were used to analyze the
biological function. And the cut-off value for significance was p < 0.05.
RESULTS: SLC14A1, SNCA, TNS1, KAT2B and PARP1 were regulated by hsa-miR-93-5p,
hsa-miR-92a-3p and hsa-miR-21-5p. Additionally, phagosome (p =
0.00627769839083361) was the only significantly enriched signal pathway involving
HLA-DOA, TUBB2A and MRC2. CONCLUSION: Disordered expression of genes under the
regulation of miRNAs may play an important role in CARAS.
PMID- 29334242
TI - Development and disease in a dish: the epigenetics of neurodevelopmental
disorders.
AB - Human neurodevelopmental disorders (NDDs) involve mutations in hundreds of
individual genes, with over-representation in genes encoding proteins that alter
chromatin structure to modulate gene expression. Here, we highlight efforts to
model these NDDs through in vitro differentiation of patient-specific induced
pluripotent stem cells into neurons. We discuss how epigenetic regulation
controls normal cortical development, how mutations in several classes of
epigenetic regulators contribute to NDDs, and approaches for modeling cortical
development and function using both directed differentiation and formation of
cerebral organoids. We explore successful applications of these models to study
both syndromic and nonsyndromic NDDs and to define convergent mechanisms,
addressing both the potential and challenges of using this approach to define
cellular and molecular mechanisms that underlie NDDs.
PMID- 29334243
TI - Facile synthesis of simple 2-oxindole-based compounds with promising
antiproliferative activity.
AB - AIM: Discovery of novel potent anticancer agents with lower side effects is a
challenge to overcome cancer, the second leading cause of death. METHODOLOGY: 2
oxindole-based hydrazides (6a-g) and benzenesulfonyl hydrazides (9a-d) were
synthesized by simple condensation reactions of the appropriate hydrazides (2a-g)
or (8a-d) with 1-ethyl-2,3-oxindolinedione (4). They were screened for their
cytotoxicity against HepG2 (liver), MCF-7 (breast), HCT116 (colon) and A549
(lung) cancer cell lines. RESULTS: The substituted benzohydrazides (6b-g)
revealed higher activity and selectivity toward the tested cell lines than
doxorubicin and 9a-d. Compound 6c exhibited the highest activity against MCF-7
cell line with IC50 = 0.0058 MUM and it induced apoptosis by caspase-3
activation, Bax upregulation and Bcl-2 downregulation in a dose-dependent manner.
CONCLUSION: This compound can be considered as a potent cytotoxic agent with
apoptotic induction property.
PMID- 29334244
TI - Evolving concepts and use of immunohistochemical biomarkers in flat non
neoplastic urothelial lesions: WHO 2016 classification update with diagnostic
algorithm.
AB - CONTEXT: The classification of flat non-neoplastic urothelial lesions has been
evolved through the years in the attempt to better define a spectrum of
morphologic entities with somewhat overlapping features. Differentiating these
lesions is important because of differences in patient management and clinical
outcome. Materials and methods and objective: A systematic review of the
literature has been carried out in order to (1) assess the most striking clinical
features of each lesion and (2) identify those morphological traits and
immunophenotypical markers which may aid in the differential diagnosis. RESULTS
AND CONCLUSION: Our results point out the importance of a proper definition of
flat non-neoplastic urothelial lesions in order to predict clinical behaviour and
allow tailored patient management; therefore, we attempted to construct a novel
and "easy to use" algorithm for a clear, standardized and evidence-based
pathological diagnosis.
PMID- 29334245
TI - Steroids from herbs of Reineckia carnea and their anticomplement activities.
AB - A new polyhydroxylated pregnane, named lbeta,2beta,3beta,4beta,5beta,6beta
hexolhydroxy-pregn-16-en-20-one (1), along with nine known (2-10) steroidal
saponins were isolated from the whole plant of Reineckia carnea. Structure
elucidations of all compounds were established by interpretation of their NMR
spectral data, HR-ESI-MS and comparing with literatures. In addition, these
compounds were evaluated with anticomplement activity. The result showed that
compound 1 exhibited anticomplement effects with the CH50 values of 0.043 mg/mL,
but saponins (2-10) showed no inhibition. Interestingly, hydrolysis of steroidal
saponins (2-10) resulted in its aglycones (2a-10a) correspondingly which showed
anticomplement activity with the CH50 values of 0.049-0.156 mg/mL.
PMID- 29334246
TI - Screening of north-east Mexico medicinal plants with activities against herpes
simplex virus and human cancer cell line.
AB - The plants examined in this study have previous biological activity reports
indicating the possibility of found activity against herpes and cancer cell. The
aim of this contribution was to carry out a screening of Juglans mollis
(Juglandaceae), Persea americana (Lauraceae), Hamelia patens (Rubiaceae), Salvia
texana (Lamiaceae), Salvia ballotaeflora (Lamiaceae), Ceanothus coeruleus
(Rhamnaceae), Chrysactinia mexicana (Asteraceae) y Clematis drummondii
(Ranunculaceae), against HeLa cells, VHS-1 and VHS-2. The method MTT was used to
determine the 50% cytotoxic concentration (CC50), in Vero and HeLa cell lines. To
determine the 50% inhibitory concentration (IC50) against herpes, the plaque
reduction method was used. Results showed that none of the plants exhibited
activity against HeLa cells. About antiherpetic activity, J. mollis and S.
ballotaeflora extracts present antiherpetic activity in terms of their SI,
increasingly interest for further studies on the isolation of compounds with
antiherpetic activity and about the mechanisms of action that produce this
activity.
PMID- 29334247
TI - Development of fisetin-loaded folate functionalized pluronic micelles for breast
cancer targeting.
AB - The natural flavonoid fisetin (FS) has shown anticancer properties but its in
vivo administration remains challenging due to its poor aqueous solubility. The
aim of the study was to develop FS loaded pluronic127 (PF)-folic acid (FA)
conjugated micelles (FS-PF-FA) by the way of increasing solubility,
bioavailability and active targetability of FS shall increase its therapeutic
efficacy. FA-conjugated PF was prepared by carbodiimide crosslinker chemistry. FS
PF-FA micelles were prepared by thin-film hydration method and evaluated in
comparison with free FS and FS loaded PF micelles (FS-PF). The smooth surfaces
with spherical in shape of FS-PF-PF micelles displayed smaller in size (103.2 +/-
6.1 nm), good encapsulation efficiency (82.50 +/- 1.78%), zeta potential (-26.7
+/- 0.44 mV) and sustained FS release. Bioavailability of FS from FS-PF-PF
micelles was increased by 6-fold with long circulation time, slower plasma
elimination and no sign of tissue toxicity as compared to free FS. Further, the
FS-PF-FA micelles demonstrated active targeting effect on folate overexpressed
human breast cancer MCF-7 cells. The concentration of the drug needed for growth
inhibition of 50% of cells in a designed time period (GI50) was 14.3 +/- 1.2
ug/ml for FS while it was greatly decreased to 9.8 +/- 0.78 ug/ml, i.e. a 31.46%
decrease for the FS-PF. Furthermore, the GI50 value for FS-PF-FA was 4.9 +/- 0.4
ug/ml, i.e. a 65.737% decrease compared to FS and 50% decrease compare to FS-PF.
The results indicate that the FS-PF-FA micelles have the potential to be applied
for targeting anticancer drug delivery.
PMID- 29334248
TI - Nigrosporanenes C and D, two new cyclohexene derivatives from the enphytic fungus
Nigrospora oryzae S4.
AB - Two new cyclohexene derivatives, nigrosporanenes C and D (1 and 2), together with
three known compounds (3-5), were isolated from the culture of an endophyte
Nigrospora oryzae S4. Their structures were characterized by a combination of
detailed spectroscopic analysis and comparison of their NMR data with those
reported in the literature. All compounds were tested for anti-phytopathogenic
activity, however, none of them showed activity at a concentration of 20 MUM.
PMID- 29334250
TI - Estimation of a Latent Variable Regression Growth Curve Model for Individuals
Cross-Classified by Clusters.
AB - The cross-classified multiple membership latent variable regression (CCMM-LVR)
model is a recent extension to the three-level latent variable regression (HM3
LVR) model which can be utilized for longitudinal data that contains individuals
who changed clusters over time (for instance, student mobility across schools).
The HM3-LVR model can include the initial status on growth effect as varying
across those clusters and allows testing of more flexible hypotheses about the
influence of initial status on growth and of factors that might impact that
relationship, but only in the presence of pure clustering of participants within
higher-level units. This Monte Carlo study was conducted to evaluate model
estimation under a variety of conditions and to measure the impact of ignoring
cross-classified data when estimating the incorrectly specified HM3-LVR model in
a scenario in which true values for parameters are known. Furthermore, results
from a real-data analysis were used to inform the design of the simulation.
Overall, it would be recommended for researchers to utilize the CCMM-LVR model
over the HM3-LVR model when individuals are cross-classified, and to use a bare
minimum of more than 100 clustering units in order to avoid overestimation of the
level-3 variance component estimates.
PMID- 29334249
TI - Antimicrobial activity of 1,3,4-oxadiazole derivatives against planktonic cells
and biofilm of Staphylococcus aureus.
AB - AIM: Staphylococcus aureus is a major cause of severe hospital-acquired
infections, and biofilm formation is an important part of staphylococcal
pathogenesis. Therefore, developing new antimicrobial agents against both
planktonic cells and biofilm of S. aureus is a major challenge. RESULTS: Three
1,3,4-oxadiazole derivatives exhibited antimicrobial activity against seven S.
aureus strains in vitro, with minimum inhibitory concentrations ranging from 4 to
32 MUg/ml. At 4 * minimum inhibitory concentration, all compounds killed cells
within 24 h, demonstrating bactericidal activity. In addition to their effects
against planktonic cells, these compounds prevented biofilm formation in a dose
dependent manner, with inhibitory concentrations for biofilm formation ranging
from 8 to 32 MUg/ml. Interestingly, higher concentrations of these compounds were
effective against mature biofilms and all compounds downregulated the
transcription of the biofilm-related gene spa. CONCLUSION: We report three new
1,3,4-oxadiazole derivatives that have bactericidal activity and could provide as
alternatives to combat S. aureus.
PMID- 29334251
TI - Discussing edaravone with the ALS patient: an ethical framework from a U.S.
perspective.
AB - The recent approval of edaravone by the United States Food and Drug
Administration has generated a mix of hope tempered by reality. The costs of the
drug, both monetarily and with regard to intensity of treatment, are high. The
benefits, while modest, will be viewed through a very different lens by
individuals depending on their goals of care. By virtue of our training and
experience, physicians are ideally suited to understand and explain new
treatments to our patients. As healthcare providers with a fiduciary
responsibility to our patients, we must make sure they are fully informed about
both the costs and benefits of non-curative therapies such as edaravone, and be
prepared to discuss these in the context of their goals of care and potential
impact on quality of life. Respect for our patients' autonomy is critical when
discussing these issues, but we should always be guided by the ethical principles
of beneficence and non-maleficence.
PMID- 29334252
TI - Impact of paternal nutrition on epigenetic patterns.
PMID- 29334253
TI - Circular RNA expression in extracellular vesicles isolated from serum of patients
with endometrial cancer.
AB - AIM: We aimed to explore the roles of circular RNAs (circRNAs) in extracellular
vesicles (EVs) isolated from serum of patients with endometrial cancer. MATERIALS
& METHODS: EVs were isolated from serum samples of three patients with stage III
adenocarcinoma aged 50-60 years and three matched healthy controls. RNA was
extracted from the EVs and analyzed using RNA-seq technique. RESULTS: We got 209
upregulated circRNAs and 66 downregulated circRNAs. Kyoto Encyclopedia of Genes
and Genomes pathway analysis indicated that the differentially expressed circRNAs
were enriched in five pathways. The expression level of hsa_circ_0109046 and
hsa_circ_0002577 was confirmed using real-time quantitative PCR. CONCLUSION: We
identified 275 differentially expressed circRNAs and the expression level of two
circRNAs was confirmed using real-time quantitative PCR.
PMID- 29334254
TI - Antioxidant and anti-proliferative properties of extracts from heterotrophic
cultures of Galdieria sulphuraria.
AB - This study explores the possibility to use the extremophilic microalga Galdieria
sulphuraria (strain 064) as a source of natural biomolecules with beneficial and
protective effects on human health. Galdieria was cultivated in heterotrophy
conditions and cells extracts for their antioxidant and anti-proliferative
properties were tested. Galdieria extracts showed high antioxidant power tested
through ABTS assay and revealed high glutathione and phycocyanin contents. Based
on Annexin-V FITC/propidium iodide and MTT analysis, algae extracts inhibited the
proliferation of human adenocarcinoma A549 cells (51.2% inhibition) through the
induction of apoptosis without cell cycle arrest. Besides, cytotoxicity and
cytometry assays showed a positive pro-apoptotic mechanism. On these bases, we
suggest that G. sulphuraria from heterotrophic culture, for its therapeutic
potential, could be considered a good candidate for further studies with the aim
to isolate bioactive anti-cancer molecules.
PMID- 29334255
TI - NGS-based methylation profiling differentiates TCF3-HLF and TCF3-PBX1 positive B
cell acute lymphoblastic leukemia.
AB - AIM: To determine whether methylation differences between mostly fatal TCF3-HLF
and curable TCF3-PBX1 pediatric acute lymphoblastic leukemia subtypes can be
associated with differential gene expression and remission. MATERIALS & METHODS:
Five (extremely rare) TCF3-HLF versus five (very similar) TCF3-PBX1 patients were
sampled before and after remission and analyzed using reduced representation
bisulfite sequencing and RNA-sequencing. RESULTS: We identified 7000
differentially methylated CpG sites between subtypes, of which 78% had lower
methylation levels in TCF3-HLF. Gene expression was negatively correlated with
CpG sites in 23 genes. KBTBD11 clearly differed in methylation and expression
between subtypes and before and after remission in TCF3-HLF samples. CONCLUSION:
KBTBD11 hypomethylation may be a promising potential target for further
experimental validation especially for the TCF3-HLF subtype.
PMID- 29334256
TI - Differential content of secondary metabolites in diploid and tetraploid cytotypes
of Siegesbeckia orientalis L.
AB - Siegesbeckia orientalis L. is an annual herb widely distributed throughout the
world and has many medicinal properties. In Chinese traditional system, it is
popularly known as Xi-Xian and used for its anti-inflammatory properties. In the
present study, two cytotypes (diploid and tetraploid) have been investigated for
their secondary metabolites. The different plant parts have been explored in
terms of total phenolics, total flavonoids, DPPH radical scavenging acitivity and
total antioxidant capacity. Out of different plant parts, leaves have the maximum
amount of secondary metabolites and antioxidant potential. HPTLC technique has
been applied to quantify six marker compounds in the two cytotypes. Tetraploid
cytotype has been compared with diploid cytotype, which shows that tetraploid has
the maximum amount of studied secondary metabolites with high antioxidant
potential.
PMID- 29334257
TI - Calaxanthones A-C, three new xanthones from the roots of Calophyllum calaba and
the cytotoxicity.
AB - Three new xanthones, named calaxanthones A-C (1-3), along with 17 known xanthones
(4-20) were isolated from the roots of Calophyllum calaba. Their structures were
determined by spectroscopic analysis. All isolated compounds were evaluated for
their cytotoxicity against five cancer cell lines (KB, HeLa S-3, HT-29, MCF-7 and
HepG-2). Compound 3 showed potent cytotoxicity against all the five cancer cell
lines with IC50 values in the range of 0.82-5.04 MUM. Furthermore, compound 6
showed potent cytotoxicity against KB, HeLa S-3 and HepG2 cells with IC50 values
of 7.06, 5.27 and 9.64 MUM, respectively. Additionally, compound 7 showed potent
cytotoxicity against KB cell with an IC50 value of 4.62 MUM.
PMID- 29334258
TI - Two new phenylpropanoid esters from Bulbophyllum retusiusculum.
AB - Two new phenylpropanoid esters bobulretulates A (1) and B (2), together with
eleven known compounds, were isolated from the whole plants of Bulbophyllum
retusiusculum. Their structures were elucidated by means of extensive
spectroscopic analysis.
PMID- 29334259
TI - Development of three-dimensional brain arteriovenous malformation model for
patient communication and young neurosurgeon education.
AB - PURPOSE: Rapid prototyping technology is used to fabricate three-dimensional (3D)
brain arteriovenous malformation (AVM) models and facilitate presurgical patient
communication and medical education for young surgeons. METHODS: Two intracranial
AVM cases were selected for this study. Using 3D CT angiography or 3D rotational
angiography images, the brain AVM models were reconstructed on personal computer
and the rapid prototyping process was completed using a 3D printer. The size and
morphology of the models were compared to brain digital subtraction arteriography
of the same patients. 3D brain AVM models were used for preoperative patient
communication and young neurosurgeon education. RESULTS: Two brain AVM models
were successfully produced. By neurosurgeons' evaluation, the printed models have
high fidelity with the actual brain AVM structures of the patients. The patient
responded positively toward the brain AVM model specific to himself. Twenty
surgical residents from residency programs tested the brain AVM models and
provided positive feedback on their usefulness as educational tool and
resemblance to real brain AVM structures. CONCLUSIONS: Patient-specific 3D
printed models of brain AVM can be constructed with high fidelity. 3D printed
brain AVM models are proved to be helpful in preoperative patient consultation,
surgical planning and resident training.
PMID- 29334260
TI - Crude extract of Origanum vulgare L. induced cell death and suppressed MAPK and
PI3/Akt signaling pathways in SW13 and H295R cell lines.
AB - Oregano (Origanum vulgare L.) is a common aromatic plant used in Mediterranean
and Asian Regions for treating respiratory diseases, painful menstruation,
rheumatoid arthritis, etc. Recently its role as an anticancer plant has been
suggested, although oregano has been never evaluated into adrenocortical tumour
cell models. This study analysed for the first time the anticancer effects of a
crude extract of wild mountain oregano (Origanum vulgare L.) in SW13 and H295R
cell lines. The crude extract was characterised by GC/MS and the toxic effects of
oregano were first analysed by brine shrimp lethality assay. Our findings
demonstrated that oregano decreased cell viability, survival, modified cell cycle
and induced cell death (through necrotic process) and that the effects can be
attributed to a blockade of MAPK and PI3 K/Akt pathways. These results suggest
that oregano extract exerts anticancer activities in adrenocortical tumour cell
lines, providing evidence for further research in higher models.
PMID- 29334261
TI - Lignans, flavonoids and coumarins from Viola philippica and their alpha
glucosidase and HCV protease inhibitory activities.
AB - Two lignans including a new one, five flavonoids and five coumarins were isolated
from the whole plant of Viola philippica (synonymised as Viola yedoensis Makino).
The new compound was structurally determined as (7R,8S,8'S) -3,3'-dimethoxy-
4,4',9-trihydroxy- 7,9'-epoxy-8,8'-lignan 9-O-rutinoside by analysis of its NMR,
MS and CD spectroscopic data. The known compounds were characterised by comparing
their NMR and MS data with those reported. Among the known compounds, 5-hydroxy
4'-methoxyflavone-7-O- rutinoside, 6,7-di-O-beta-D- glucopyranosylesculetin, and
7R,8S-dihydrodehydrodiconiferyl alcohol 4-O-beta-D- glucopyranoside were isolated
and identified from this genus for the first time. Of these compounds, 5-hydroxy
4'-methoxyflavone-7-O-rutinoside and (7R,8S,8'S) -3,3'-dimethoxy- 4,4',9
trihydroxy- 7,9'-epoxy-8,8'-lignan 9-O-rutinoside were potently active against
alpha-glucosidase, while the two dimeric coumarins, 5, 5'-bi (6, 7
dihydroxycoumarin) and 6,6',7,7'-tetrahydroxy-5,8'-bicoumarin potently inhibited
HCV protease.
PMID- 29334262
TI - A multicentre study on unattended automated office blood pressure measurement in
treated hypertensive patients.
AB - AIMS: Unattended automated office blood pressure (uAutoOBP) may eliminate white
coat effect. In the present study, we studied its relationships to attended
office blood pressure (BP) and ambulatory BP monitoring (ABPM). MATERIAL AND
METHODS: Stable treated hypertensive subjects were examined in four Czech
academic hypertension centres. uAutoOBP was measured with the BP Tru device;
attended BP was measured six times: three times with auscultatory method
(AuscOBP) by the physician followed optionally by three oscillometric
measurements (OscOBP). ABPM was performed within one week from the clinical
visit. RESULTS: Data on 172 subjects aged 63.7 +/- 12.4 years with AuscOBP 127.6
+/- 12.1/77.6 +/- 10.0 mm Hg are reported. uAutoOBP was by 8.5 +/- 9.0/3.0 +/-
6.1 mm Hg lower than AuscOBP. The AuscOBP-uAutoOBP difference increased with the
AuscOBP level and it did not depend on any other factor. OscOBP differed by 8.6
+/- 8.6/1.9 +/- 5.7 mm Hg from uAutoOBP. 24-hour mean BP was by 4.2 +/- 12.1/3.5
+/- 7.8 mm Hg lower than AuscOBP and by 4.3 +/- 11.0/0.5 +/- 6.9 mm Hg higher
than uAutoOBP; the correlation coefficients of 24-hour mean BP with AuscOBP and
with uAutoOBP did not differ (p for difference >=.13). In the lowest BP group
(systolic AuscOBP <120 mm Hg or diastolic AuscOBP <70 mm Hg), both AuscOBP and
uAutoOBP were lower than 24-hour mean BP, while in the highest BP group (systolic
AuscOBP >=140 mm Hg or diastolic AuscOBP >=90 mm Hg), they were higher.
CONCLUSIONS: Compared to uAutoOBP, attended BP measurement gives higher values,
both when measured with auscultatory or oscillometric method. Inter-individual
variability of AutoOBP - uAuscOBP difference, as well of uAutoOBP - ABPM
difference, is large. We did not prove that uAutoOBP would be associated to 24
hour ambulatory BP more closely than attended BP.
PMID- 29334263
TI - New cytotoxic natural products from the mangrove biome: covering the period 2007
2015.
AB - Nowadays, the mangrove biome is considered to be a profound resource of natural
products usually possessing cytotoxicity of a broader range. Covering the period
2007-2015, a total of 21 new naturally occurring compounds has stood out. For
example, xylogranin B and swietephragmin C were found to exhibit very potent
cytotoxic activity against the colon HCT-116 cells reaching IC50 values of 0.05
and 0.06 MUM, respectively. Bearing in mind the efficacy of the majority
compounds in the preliminary in vitro screens, these studies should be expanded
to both ex vivo and in vivo screens including the evaluation of the relevant
toxicological profiles.
PMID- 29334264
TI - Antifungal activity of phenolic monoterpenes and structure-related compounds
against plant pathogenic fungi.
AB - The aim of this work is to explore the possibility of using the phenolic
monoterpenes (PMs) as leading compounds with antifungal activity against plant
disease. The in vitro antifungal activities of carvacrol and thymol against seven
kinds of plant pathogenic fungi were evaluated on mycelium growth rate method,
and the results showed that carvacrol and thymol exhibited broad spectrum
antifungal activity. Structure requirement for the antifungal activity of PMs was
also investigated. The preliminary conclusion was that phenolic hydroxyl and
monoterpene were basic structures for the antifungal activity of PMs, and the
position of phenolic hydroxyl showed less effect. Ester derivatives of carvacrol
and thymol were more effective than carvacrol and thymol against plant pathogenic
fungi. We suggested that carvacrol, thymol and their ester derivatives could
potentially be used as new fungicide leading compounds.
PMID- 29334265
TI - Prevalence and covariates of uncontrolled hypertension in ischemic stroke
survivors: the Norwegian stroke in the young study.
AB - PURPOSE: Hypertension is the most important modifiable risk factor for stroke.
Few data are available on control of hypertension in younger ischemic stroke
survivors. MATERIAL AND METHODS: We assessed clinic and ambulatory blood pressure
(BP) measurements in 320 patients aged 15-60 years (mean 48 +/- 10) included in
the Norwegian Stroke in the Young Study during 3-months follow-up after the index
stroke. Controlled hypertension was defined as ambulatory BP <130/80 mmHg.
Carotid-femoral pulse wave velocity (PWV) was measured by applanation tonometry.
Carotid plaque was considered present if focal intima-media thickness >1.5 mm.
RESULTS: At hospital discharge, 58% of the patients were treated for
hypertension. Another 9% of the total study population was diagnosed with new
onset hypertension during follow-up. At the 3-months follow-up visit, 56% of
patients with treated hypertension were uncontrolled. Patients with uncontrolled
treated hypertension were older, had higher body mass index (BMI) and PWV, and
were more likely to have diabetes and carotid plaques compared to patients with
normotension (p < .01). Compared to controlled treated hypertension, patients
with uncontrolled treated hypertension had higher prevalence of carotid plaque (p
< .01). In a multivariate logistic regression, uncontrolled treated hypertension
was associated with higher PWV and BMI, and presence of carotid plaque,
independent of the more intensified use of antihypertensive treatment (all p <
.05). CONCLUSION: Uncontrolled hypertension was highly prevalent in ischemic
stroke survivors <60 years and associated with co-presence of obesity and
functional and structural arterial damage. Our results highlight the unmet
potential and challenge of optimization of hypertension diagnosis and management
in order to prevent recurrent vascular events in ischemic stroke survivors.
PMID- 29334266
TI - Hyaluronic acid modified daunorubicin plus honokiol cationic liposomes for the
treatment of breast cancer along with the elimination vasculogenic mimicry
channels.
AB - BACKGROUND: Breast cancer is an alarming global public health problem and a main
cause of cancer-related death in women. Systemic chemotherapy is the most widely
used treatment for breast cancer. However, current chemotherapy treatments are
far from desirable due to poor targeting specificity, severe side effects and
vasculogenic mimicry (VM). PURPOSE: Hyaluronic acid (HA)-modified daunorubicin
plus honokiol (HNK) cationic liposomes were prepared and characterised for
treatment of breast cancer by eliminating VM. METHODS: HA-modified daunorubicin
plus HNK cationic liposomes were prepared by a thin-film hydration method.
Evaluations were performed on MCF-7 cells and MDA-MB-435S cells, which are human
breast cancer cells, and xenografts of MDA-MB-435S cells. RESULTS: In vitro
results revealed that the HA-modified daunorubicin plus HNK cationic liposomes
enhanced the cellular uptake and destroyed VM channels. In vivo results
demonstrated that the liposomes prolonged the circulation time in the blood,
obviously accumulated in the tumour region, and enhanced the overall anticancer
effects. Action mechanisms were related to down-regulation of VM protein
indicators including FAK, EphA2, MMP-2 and MMP-9. CONCLUSIONS: The prepared HA
modified daunorubicin plus HNK cationic liposomes may serve as a promising
therapeutic strategy for the treatment of breast cancer.
PMID- 29334268
TI - Analysis of the development and progression of carbon monoxide poisoning-related
acute kidney injury according to the Kidney Disease Improving Global Outcomes
(KDIGO) criteria.
AB - CONTEXT: Acute kidney injury (AKI) can occur after carbon monoxide (CO)
intoxication; however, limited data are available. This study aimed to evaluate
the prognostic value of the development and progression of AKI in patients with
acute CO poisoning. MATERIALS AND METHODS: We conducted a retrospective cohort
study using a prospective registry of CO poisoning between January 2010 and
December 2015. AKI was defined and classified according to the Kidney Disease
Improving Global Outcomes (KDIGO) criteria. Multivariate logistic regression
analysis was conducted to determine the association between AKI and adverse
outcomes, defined as neurological deficits at discharge or 28-day mortality.
RESULTS: A total of 661 patients were evaluated. According to KDIGO criteria, 114
patients (17.2%) had AKI (initial: stage 1, 70.2%; stage 2, 26.3%; stage 3, 3.5%)
on admission and 119 (18.0%) finally developed AKI during their hospital stay
(maximum: stage 1, 68.9%; stage 2, 23.5%; stage 3, 7.6%). Almost all patients
(99.2%) were diagnosed as having their highest KDIGO stage within three days
(median, one day). AKI development was associated with adverse outcomes (odds
ratio (OR) 17.53, 95% confidence interval 45.00-77.14). Both initial and maximum
AKI stages demonstrated a stepwise increase of adjusted OR for adverse outcomes.
AKI stage progression occurred in 8.4% of patients with AKI and was an
independent factor for adverse outcomes. CONCLUSION: CO poisoning- related AKI
occurred in 18% and was mostly detected within one day after CO intoxication. The
development and progression of AKI had a strong association with adverse outcomes
and deserve further prospective investigation.
PMID- 29334269
TI - Effects of a transient noise reduction algorithm on speech intelligibility in
noise, noise tolerance and perceived annoyance in cochlear implant users.
AB - OBJECTIVE: To evaluate the validity and efficacy of a transient noise reduction
algorithm (TNR) in cochlear implant processing and the interaction of TNR with a
continuous noise reduction algorithm (CNR). DESIGN: We studied the effects of TNR
and CNR on the perception of realistic sound samples with transients, using
subjective ratings of annoyance, a speech-in-noise test and a noise tolerance
test. STUDY SAMPLE: Participants were 16 experienced cochlear implant recipients
wearing an Advanced Bionics Naida Q70 processor. RESULTS: CI users rated sounds
with transients as moderately annoying. Annoyance was slightly, but significantly
reduced by TNR. Transients caused a large decrease in speech intelligibility in
noise and a moderate decrease in noise tolerance, measured on the Acceptable
Noise Level test. The TNR had no significant effect on noise tolerance or on
speech intelligibility in noise. The combined application of TNR and CNR did not
result in interactions. CONCLUSIONS: The TNR algorithm was effective in reducing
annoyance from transient sounds, but was not able to prevent a decreasing effect
of transients on speech understanding in noise and noise tolerance. TNR did not
reduce the beneficial effect of CNR on speech intelligibility in noise, but no
cumulated improvement was found either.
PMID- 29334270
TI - Secukinumab in multi-failure psoriatic patients: the last hope?
AB - Psoriasis is a multi-systemic chronic inflammatory disease that affects about 1.5
3% of the general population, of which almost 20% suffer from a moderate-severe
form. Those patients can be treated with a systemic agent and in case of scarce
response or contraindications, they may require a biologic therapy, such as tumor
necrosis factor or interleukin-12/23 inhibitors. When also these agents fail,
clinicians face a true therapeutic challenge. We report a case series of multi
failure 16 patients, successfully treated with secukinumab, a human monoclonal
antibody that selectively neutralizes interleukin-17 A and is recently approved
for the treatment of plaque psoriasis, psoriatic arthritis, and ankylosing
spondylitis.
PMID- 29334271
TI - The safety of available treatments of male hypogonadism in organic and functional
hypogonadism.
AB - INTRODUCTION: In the case of primary male hypogonadism (HG), only testosterone
(T) replacement therapy (TRT) is possible whereas when the problem is secondary
to a pituitary or hypothalamus alteration both T production and fertility can be,
theoretically, restored. We here systematically reviewed and discussed the
advantages and limits of medications formally approved for the treatment of HG.
Areas covered: Data derived from available meta-analyses of placebo controlled
randomized trials (RCTs) were considered and analyzed. Gonadotropins are well
toleratedand their use is mainly limited by higher costs and a more cumbersome
treatment schedule than TRT. Available RCTs on TRT suggest that cardiovascular
(CV) and venous thromboembolism risk is not a major issue and that prostate
safety is guaranteed. The risk of increased hematocrit is mainly limited to the
use of short terminjectable preparations. Expert opinion: In the last few years
the concept of 'organic' irreversible HG and 'functional' or age- and comorbidity
related HG has been introduced. This definition is not evidence-based. The
majority of RCTs enrolled patients with 'functional' HG. Considering the
significant improvement in body composition, glucose metabolism and sexual
activity, TRT should not be limited to 'organic' HG, but also offered for
'functional'.
PMID- 29334273
TI - The Barthel Index and the Cumulated Ambulation Score are superior to the de
Morton Mobility Index for the early assessment of outcome in patients with a hip
fracture admitted to an acute geriatric ward.
AB - PURPOSE: To examine clinimetric properties of the de Morton Mobility Index
(DEMMI) in patients with hip fracture in comparison with the modified Barthel
Index (BI), Cumulated Ambulation Score (CAS), and 30-s Chair Stand Test (30-s
CST). MATERIALS AND METHODS: Two hundred and twenty two patients with a hip
fracture admitted to a geriatric ward following surgery were assessed on day 1
and at discharge (mean of 9 [SD 5.1] post-surgery days). RESULTS: Ninety eight
percent and 89% of patients were not able to perform the 30-s CST at baseline and
at discharge (large floor effect), respectively. Corresponding floor effects were
39% and 31% for DEMMI, 12% and 5% for BI, and 22% and 6%, respectively, for CAS.
Convergent validity was strong between DEMMI and CAS (r = 0.76, 95% CI: 0.69
0.81), and moderate between DEMMI and BI (r = 0.58, 95% CI: 0.48-0.66) and CAS
and BI (r = 0.49, 95% CI: 0.39-0.59). Responsiveness, as indicated by the effect
size was 0.76 for DEMMI, 1.78 for BI and 1.04 for CAS. Baseline scores of DEMMI,
BI, and CAS showed similar properties in predicting discharge destination of
patients from own home. CONCLUSIONS: The value of using DEMMI and 30-s CST in
patients with hip fracture during the acute hospitalization seems limited in
comparison with BI and CAS. DEMMI and CAS seem to assess similar constructs.
Implications for Rehabilitation Outcome measures used for the evaluation of
patients with hip fracture should be validated in the specific time-line and
rehabilitation setting following surgery, before being implemented in daily
clinical practice. We suggest the Cumulated Ambulation Score for monitoring basic
mobility during the acute hospitalization for the entire group of patients
recovering from a hip fracture, while DEMMI seems more feasible for the subgroup
of patients with higher functional levels. The modified Barthel Index seems
useful for the assessment of activities of daily living in the acute care setting
of patients with hip fracture. We cannot recommend the original 30-s Chair Stand
Test to be used for the evaluation of patients with hip fracture in the acute
hospital setting.
PMID- 29334272
TI - Extracellular vesicle-mimetic nanovesicles transport LncRNA-H19 as competing
endogenous RNA for the treatment of diabetic wounds.
AB - Diabetic wounds, one of the most enervating complications of diabetes mellitus,
affect millions of people worldwide annually. Vascular insufficiency, caused by
hyperglycemia, is one of the primary causes and categories of diabetic impaired
wound healing. Recently, long noncoding RNA (LncRNA)-H19, which is significantly
decreased in diabetes and may be crucial in triggering angiogenesis, has
attracted increasing interest. The possible relationship between the decrease of
LncRNA-H19 and the impairment of angiogenesis in diabetes could involve
impairment of the insulin-phosphatidylinositol 3-kinase (PI3K)-Akt pathway via
the interdiction of LncRNA-H19. Thus, a therapeutic strategy utilizing LncRNA-H19
delivery is feasible. In this study, we investigated the possibility of using
high-yield extracellular vesicle-mimetic nanovesicles (EMNVs) as an effective
nano-drug delivery system for LncRNA, and studied the function of EMNVs with a
high content of LncRNA-H19 (H19EMNVs). The results, which were exciting, showed
that H19EMNVs had a strong ability to neutralize the regeneration-inhibiting
effect of hyperglycemia, and could remarkably accelerate the healing processes of
chronic wounds. Our results suggest that bioengineered EMNVs can serve as a
powerful instrument to effectively deliver LncRNA and will be an extremely
promising multifunctional drug delivery system in the immediate future.
PMID- 29334274
TI - An overview of robotic/mechanical devices for post-stroke thumb rehabilitation.
AB - PURPOSE: This article aims to clarify the current state-of-the-art of
robotic/mechanical devices for post-stroke thumb rehabilitation as well as the
anatomical characteristics and motions of the thumb that are crucial for the
development of any device that aims to support its motion. METHODS: A systematic
literature search was conducted to identify robotic/mechanical devices for post
stroke thumb rehabilitation. Specific electronic databases and well-defined
search terms and inclusion/exclusion criteria were used for such purpose. A
reasoning model was devised to support the structured abstraction of relevant
data from the literature of interest. RESULTS: Following the main search and
after removing duplicated and other non-relevant studies, 68 articles
(corresponding to 32 devices) were left for further examination. These articles
were analyzed to extract data relative to (i) the motions assisted/permitted -
either actively or passively - by the device per anatomical joint of the thumb
and (ii) mechanical-related aspects (i.e., architecture, connections to thumb,
other fingers supported, adjustability to different hand sizes, actuators - type,
quantity, location, power transmission and motion trajectory). CONCLUSIONS: Most
articles describe preliminary design and testing of prototypes, rather than the
thorough evaluation of commercially ready devices. Defining appropriate kinematic
models of the thumb upon which to design such devices still remains a challenging
and unresolved task. Further research is needed before these devices can actually
be implemented in clinical environments to serve their intended purpose of
complementing the labour of therapists by facilitating intensive treatment with
precise and repeatable exercises. Implications for Rehabilitation Post-stroke
functional disability of the hand, and particularly of the thumb, significantly
affects the capability to perform activities of daily living, threatening the
independence and quality of life of the stroke survivors. The latest studies show
that a high-dose intensive therapy (in terms of frequency, duration and
intensity/effort) is the key to effectively modify neural organization and
recover the motor skills that were lost after a stroke. Conventional therapy
based on manual interaction with physical therapists makes the procedure labour
intensive and increases the costs. Robotic/mechanical devices hold promise for
complementing conventional post-stroke therapy. Specifically, these devices can
provide reliable and accurate therapy for long periods of time without the
associated fatigue. Also, they can be used as a means to assess patients?
performance and progress in an objective and consistent manner. The full
potential of robot-assisted therapy is still to be unveiled. Further exploration
will surely lead to devices that can be well accepted equally by therapists and
patients and that can be useful both in clinical and home-based rehabilitation
practice such that motor recovery of the hand becomes a common outcome in stroke
survivors. This overview provides the reader, possibly a designer of such a
device, with a complete overview of the state-of-the-art of robotic/mechanical
devices consisting of or including features for the rehabilitation of the thumb.
Also, we clarify the anatomical characteristics and motions of the thumb that are
crucial for the development of any device that aims to support its motion.
Hopefully, this?combined with the outlined opportunities for further
research?leads to the improvement of current devices and the development of new
technology and knowledge in the field.
PMID- 29334275
TI - Laparoscopic ovarian drilling versus GnRH antagonist combined with cabergoline as
a prophylaxis against the re-development of ovarian hyperstimulation syndrome.
AB - OBJECTIVE: The aim of this work was to investigate the value of laparoscopic
ovarian drilling (LOD) compared with GnRH antagonist flexible protocol combined
with cabergoline (Cb), as a prophylaxis against the re-development of ovarian
hyperstimulation syndrome (OHSS) in women with clomiphene citrate-resistant
polycystic ovary disease (CCR-PCOD) who had severe OHSS before in a previous ICSI
cycle. STUDY DESIGN: It is a prospective controlled study, where 250 CCR-PCOD
women (n = 250) with a history of severe OHSS before, had been recruited for the
study. LOD had been performed for 120 (n = 120) of the recruited women before
ovarian induction, and considered as group A. GnRH antagonist (Cetrotide 0.25 mg)
was added when a leading follicle reaches 14-16 mm combined with oral Cb in a
dose 0.5 mg a day before hCG, and for 8 d for another 130 (n = 130) women, and
considered as group B. Pregnancy was diagnosed with BhCG level >=25 IU/L, +/- 14
d after embryo transfer, followed with transvaginal ultrasound scanning (TVS) 2
weeks later to confirm intra-uterine pregnancy (IUP). Women were followed up
weekly for 3 months for the possible development of any signs and symptoms of
OHSS. RESULTS: None of the participants in group A developed severe OHSS, and
only six women (5%) developed mild to moderate OHSS. The incidence of severe OHSS
was significantly higher (n = 3, 15%) in group B compared with group A (p <
.001). Another (n = 17, 13.3%) women in group B developed mild to moderate OHSS.
The probability of developing severe OHSS was also significantly higher in group
B as well (p = .031). Pregnancy rate (PR) was significantly higher in group A
more than group B (67% versus 39%, respectively), and all were single
intrauterine pregnancies (IUP) and all developed after fresh embryo transfer
(ET), compared with frozen embryo transfer (FET) which was performed in 42 cases
in group B after postponing ET due to significantly severe OHSS developed.
CONCLUSION: LOD could be considered a good prophylactic measure against OHSS, in
addition to improving the total outcome of IVF cycles in women with CCR-PCOS.
PMID- 29334277
TI - Validation of DPOAE screening conducted by village health workers in a rural
community with real-time click evoked tele-auditory brainstem response.
AB - OBJECTIVE: This study assessed the validity of DPOAE screening conducted by
village health workers (VHWs) in a rural community. Real-time click evoked tele
auditory brainstem response (tele-ABR) was used as the gold standard to establish
validity. DESIGN: A cross-sectional design was utilised to compare the results of
screening by VHWs to those obtained via tele-ABR. Study samples: One hundred and
nineteen subjects (0 to 5 years) were selected randomly from a sample of 2880
infants and young children who received DPOAE screening by VHWs. METHOD: Real
time tele-ABR was conducted by using satellite or broadband internet connectivity
at the village. An audiologist located at the tertiary care hospital conducted
tele-ABR testing through a remote computing paradigm. Tele-ABR was recorded using
standard recording parameters recommended for infants and young children. Wave
morphology, repeatability and peak latency data were used for ABR analysis.
RESULTS: Tele-ABR and DPOAE findings were compared for 197 ears. The sensitivity
of DPOAE screening conducted by the VHW was 75%, and specificity was 91%. The
negative and positive predictive values were 98.8% and 27.2%, respectively.
CONCLUSIONS: The validity of DPOAE screening conducted by trained VHW was
acceptable. This study supports the engagement of grass-root workers in community
based hearing health care provision.
PMID- 29334276
TI - An automatic measure of progression during colonoscopy correlates to patient
experienced pain.
AB - BACKGROUND: Colonoscopy screening and surveillance programs depend on patient's
tolerable experience, which is associated with competence of the endoscopist. The
Colonoscopy Progression Score (CoPS) is an automated tool based on recording of
the Magnetic Scope Imager (MEI) picture in order to track progression. CoPS
deliver a numeric score and a graphic map. A high score expresses a rapid and
smooth progression. Aims of study were to explore the correlation between CoPS
and patient experienced pain and to identity locations associated with pain.
METHODS AND MATERIALS: Patients listed for colonoscopy were included and asked to
reply to pain by pressing a rubber ball. The signal was recorded simultaneous to
CoPS. Patients evaluated the experience on a Visual Analogue Scale (VAS). CoPS
and recorded pain events were used to create a pain sensitive CoPS-map (S-CoPS
map). RESULTS: A total of 58 complete recordings were used for evaluation. We
demonstrated a moderate correlation between CoPS and patient experienced pain,
Pearson's r = -0.47 (p < .001). A low CoPS was associated with a painful
colonoscopy and a high CoPS excluded severe pain. Sensitivity and specificity was
0.79 and 0.60 and AUC was 0.61 Passage of the sigmoid colon, right and left
flexures were associated with pain for 51%, 33% and 25% of the patients,
respectively. CONCLUSION: A moderate correlation between CoPS and patient
experienced pain suggest that CoPS measure inserting skills but might also be a
measure of a gentle performance. The graphic S-CoPS-map can be used to point-out
painful passages and aid planning of future colonoscopies.
PMID- 29334278
TI - A comparative safety review between GLP-1 receptor agonists and SGLT2 inhibitors
for diabetes treatment.
AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium
glucose cotransporter 2 inhibitors (SGLT2i) are of particular interest in type 2
diabetes treatment strategies, due to their efficacy in reducing HbA1c with a low
risk of hypoglycaemia, to their positive effects on body weight and blood
pressure and in light of their effects on cardiovascular risk and on
nephroprotection emerged from the most recent cardiovascular outcome trials.
Since it is therefore very likely that GLP-1RA and SGLT2i use will become more
and more common, it is more and more important to gather and discuss information
about their safety profile. Area Covered: adverse events and the safety concerns
most often emerged in trials with GLP-1RA namely, exenatide long acting release
(LAR), dulaglutide, liraglutide, semaglutide, lixisenatide or SGLT2i, namely
empagliflozin, dapagliflozin, canagliflozin and SGLT2i with an attempt at
comparing the safety profiles of molecules of these two classes. Expert opinion:
GLP-1RA and SGLT2i, although each associated with different specific side
effects, share a 'similar' safety profile and are both drugs relatively easy to
handle. The potentially complementary mechanisms of action, the cardio and
nephroprotective effects demonstrated by molecules of both classes, make these
drugs potentially useful even in add on to each other.
PMID- 29334279
TI - Uric acid and the vaccine adjuvant activity of aluminium (oxy)hydroxide
nanoparticles.
AB - In an effort to improve the adjuvanticity of insoluble aluminium salts, we
discovered that the adjuvant activity of aluminium salt nanoparticles is
significantly stronger than aluminium salt microparticles, likely related to
nanoparticle's stronger ability to directly activate NACHT, LRR and PYD domains
containing protein 3 (NLRP3) inflammasome as the nanoparticles are more
efficiently taken up by phagocytic cells. Endogenous signals such as uric acid
from cell damage or death caused by the cytotoxicity of aluminium salts are
thought to indirectly activate inflammasome, prompting us to hypothesise that the
potent adjuvant activity of aluminium salt nanoparticles is also related to their
ability to stimulate uric acid production. In the present study, we prepared
aluminium (oxy)hydroxide nanoparticles (~ 30-100 nm) and microparticles (X50,
9.43 MUm) and showed that intraperitoneal injection of mice with the
nanoparticles, absorbed with ovalbumin, led to a significant increase in uric
acid level in the peritoneal lavage, whereas the microparticles did not. The
aluminium (oxy)hydroxide nanoparticles' ability to stimulate uric acid production
was also confirmed in cell culture. We concluded that the stronger adjuvant
activity of insoluble aluminium (oxy)hydroxide nanoparticles, relative to
microparticles, may be attributed at least in part to their stronger ability to
induce endogenous danger signals such as uric acid.
PMID- 29334280
TI - Comparison of guidelines for the use of TNF inhibitors for psoriasis in the
United States, Canada, Europe and the United Kingdom: a critical appraisal and
comprehensive review.
AB - PURPOSE: To compare and contrast evidence-based CPGs from leading dermatological
organizations for the use of tumor necrosis factor inhibitors (TNFi) in
psoriasis. MATERIALS AND METHODS: Guidelines from the British National Institute
for Health and Care Excellence (NICE), the British Association of Dermatologists
(BAD), the American Academy of Dermatology (AAD), the National Psoriasis
Foundation (NPF), and the Canadian Dermatology Association (CDA) were reviewed
and compared. RESULTS: Various guidelines are similar regarding treatment
initiation but have significant differences regarding topics such as continuous
versus intermittent therapy, use in erythrodermic and pustular palmoplantar
psoriasis and special patient populations. CONCLUSION: TNF inhibitors remain
valuable tools in psoriasis therapy, and guidelines for their use may help
clinicians use them effectively.
PMID- 29334281
TI - Learning with unwell patients in the intensive care unit.
PMID- 29334282
TI - Evaluation of dentin permeability of fluorotic permanent teeth.
AB - OBJECTIVE: The in vitro permeability characteristics of dentin have been studied
extensively and used to evaluate the efficacy of various preventative and
restorative procedures. The aim of this in vitro study was to precisely determine
the dentin permeability of fluorotic premolar teeth using an electronic hydraulic
conductance measurement system with photosensors and to compare the data with
healthy premolars. METHODS: In total, 40 fluorotic and healthy premolar teeth
with complete root formation that were extracted for orthodontic purposes and had
no caries, restoration, fractures, or cracks were selected for this study. Teeth
were classified according to a modified form of the dental fluorosis index of
Thylstrup and Fejerskov. The dentin discs were placed in an electronic hydraulic
conductance measurement system equipped with photosensors, which was designed for
measurements of dentin permeability. The amount of distilled water passed through
each dentin disc (MUL/min) under a constant pressure was determined. Dentin
permeability data of the fluorotic and healthy teeth were recorded and analyzed
statistically. RESULTS: The present study showed that fluorosis influenced the
volume of fluid that passed through the dentin and the dentin permeability was
decreased, whereas dental fluorosis severity was increased in permanent teeth.
CONCLUSION: The number of teeth with fluorosis is increasing, depending on
fluorine sources, so more appropriate treatments will need to be evaluated by
standardizing the methods employed in related studies.
PMID- 29334283
TI - Effects of an exercise program on the physiological, biological and psychological
profiles in patients with mood disorders: a pilot study.
AB - OBJECTIVE: The objective of this study is to assess the impact of an 8-week
physical training program on physiological, biological and psychological profiles
in individual with mood disorders. METHODS: Seven patients participated in the
study. Patients were trained twice weekly (75 min/session) for 8 weeks. The
training program aimed to improve muscular and cardiorespiratory reserves as well
as functional capacity. Bioassays were also measured (lipid profile, blood
glucose and cortisol). Depression, sleep quality and body image dissatisfaction
were assessed. All measures were administrated at pre/post-intervention. RESULTS:
At post-intervention, 13 of the 15 physiological fitness, muscular strength and
functional capacity variables improved significantly (p < .05). In addition,
change in cortisol levels represented a medium to large effect size (Cohen's d =
0.67) which indicates a clinical reduction of stress-related symptoms. Depression
was significantly improved (Cohen's d = -0.47; p = .027). Sleep and body image
showed a trend-level improvement. CONCLUSIONS: An 8-week periodised training
program improved physiological, biological and psychological profiles in patients
with mood disorders.
PMID- 29334284
TI - Surface endoglin (CD105) expression on acute leukemia blast cells: an extensive
flow cytometry study of 1002 patients.
PMID- 29334285
TI - What should we mean by "allowed to supervise others" in entrustment scales?
PMID- 29334286
TI - An editorial on the article 'Patents in the Diabetes Area in the Years 2008
2016'.
PMID- 29334287
TI - Efficacy and safety of alpha blockers in medical expulsive therapy for ureteral
stones: a mixed treatment network meta-analysis and trial sequential analysis of
randomized controlled clinical trials.
AB - INTRODUCTION: Alpha blockers (AB) are the main group of drugs used for medical
expulsive therapy (MET) in patients with ureteral stones. However, there is no
consensus on the relative efficacy and safety of individual AB in MET. Areas
covered: The present work is a network meta-analysis of randomized controlled
trials comparing AB with either placebo or standard of care in patients with
ureteral stones. Electronic databases of Medline, Cochrane CENTRAL and Google
Scholar were searched for eligible clinical studies. Inverse variance
heterogeneity model was used for mixed treatment comparisons. Stone expulsion
rate (SER) and stone expulsion time (SET) were the primary outcomes. Sub-group
analyses for the following sub-groups were carried out: children; after shockwave
lithotripsy; stone size of <=5 mm; >5 mm; proximal and distal ureteral stones.
Expert review: AB, phosphodiesterase inhibitors and combined AB with
corticosteroids were observed with significant stone expulsion rate compared to
control group in a recent network meta-analysis. Due to lack of head-to-head
clinical trials within AB, only tamsulosin has been widely recommended by various
urological guidelines. The results of this network meta-analysis will guide the
future researchers in evaluating other promising ABs as agents for MET.
PMID- 29334288
TI - Targeted anti-IL-13 therapies in asthma: current data and future perspectives.
AB - INTRODUCTION: The identification of patients with severe asthma who will benefit
from a personalized management approach remains an unmet need. Interleukin-13 (IL
13) is a cytokine possessing a significant role in asthma pathogenesis and
progression of disease. Humanised monoclonal antibodies against IL-13 and IL-13
and IL-4 receptors are mainly proposed as add-on therapy in patients with TH2
high inflammation with uncontrolled asthma despite maximum therapy. Areas
covered: The role of IL-13 in airway inflammation in severe asthma, the targeted
anti-IL-13 therapies and biomarkers that predict response to anti-IL-13 treatment
are discussed. Expert opinion: New effective individualized therapies in severe
asthma are urgently needed to block specific inflammatory pathways using
monoclonal antibodies. Studies on anti-IL-13 therapies showed that asthmatic
patients could benefit from this novel targeted therapy as far as lung function
and exacerbation rate are concerned. TH2-high and especially periostin-high
groups of asthmatics with moderate-to-severe uncontrolled asthma seem to compose
the group that could benefit from anti-IL-13 therapy. Targeting IL-13 alone may
not be sufficient to achieve asthma control. Inhibition of IL-13 and IL-4 with
mabs may be more encouraging and patients will probably have additional benefits
from these therapeutic interventions because of IL-13/IL-4 overlapping actions in
asthma pathophysiology.
PMID- 29334289
TI - The extracellular matrix-degrading protein ADAMTS5 is expressed in the nuclei of
urothelial cells in healthy rats.
AB - OBJECTIVE: The aim of this study was to investigate whether protein expression of
the extracellular matrix-degrading protease ADAMTS5 can be demonstrated in the
urinary bladder of healthy rats, and, if so, to determine the localization of
this enzyme. MATERIALS AND METHODS: The experiments were conducted with eight
inbred male Sprague-Dawley rats. Immunohistochemistry was used to investigate the
expression of ADAMTS5 in the urinary bladder. Negative controls were established
by either excluding the primary antibody or applying the antibody after it had
been preabsorbed with its immunogenic peptide. Confocal microscopy was used to
visualize the distribution of ADAMTS5 in the urinary bladder tissue. RESULTS:
Immunoreactivity for ADAMTS5 was demonstrated in the urothelium and in the
detrusor. This expression was localized not only in the cytoplasm, but also in
the nuclei. Confocal microscopy corroborated these findings. CONCLUSION:
Expression of ADAMTS5 was demonstrated in the cytoplasm as well as in the nuclei
of the urothelium and detrusor cells, suggesting that it may play a role at the
transcriptional level.
PMID- 29334290
TI - Topical lidocaine-prilocaine cream versus lidocaine infiltration for pain relief
during repair of perineal tears after vaginal delivery: randomized clinical
trial.
AB - OBJECTIVE: The current study aims to compare the analgesic effect of lidocaine
prilocaine (LP) cream with lidocaine infiltration during repair of perineal tears
after vaginal delivery. MATERIALS AND METHODS: A single center open-labeled
randomized clinical trial was carried out in a tertiary University Hospital
between October 2016 and May 2017 (Clinical Trials.Gov: NCT02883179). We included
parous women, who delivered at gestational age >37 weeks with first- or second
degree perineal tears. The participants were randomized in a 1:1 ratio to either
lidocaine infiltration (Group I); or application of LP cream (Group II) for pain
relief during perineal repair. The primary outcome was the difference in mean
pain score during perineal repair. Secondary outcomes included the participants'
satisfaction, the need for additional anesthesia, the duration of perineal
repair, and the rate of adverse effects of both medications. RESULTS: The study
included 144 participants randomized to both groups. The mean pain score during
perineal repair was significantly lower in the LP cream group (3.86 +/- 1.59)
than the lidocaine infiltration group (5.99 +/- 1.47) [p = .001]. The duration of
repair was significantly shorter in the LP group than the lidocaine infiltration
group (6.37 +/- 3.68 versus 8.17 +/- 2.75 min, respectively, p = .001). The need
for additional anesthesia was quite similar in both groups (p = .371). More women
in the LP cream group were satisfied than the other group with statistical
significant difference (76.4 versus 30.6%, p = .000). No difference between side
effects in both groups (p = .171) Conclusions: Topical application of lidocaine
prilocaine cream is an effective analgesic during repair of perineal tears with
no harmful side effects.
PMID- 29334291
TI - Prevalence and risk factors of hyperprolactinemia among patients with various
psychiatric diagnoses and medications.
AB - OBJECTIVES: Hyperprolactinemia is a common adverse event associated with
psychotropic medications (mainly antipsychotics) used in the management of
schizophrenia and bipolar disorders. The aim of this study was to estimate the
prevalence of hyperprolactinemia in psychiatric patients and to evaluate its
association with various psychiatric diagnoses and the use of various
psychotropic medications. METHODS: A cross-sectional observational study was
conducted between July 2012 and June 2014. Patients were recruited from a number
of hospitals located in the five regions of Saudi Arabia. Hyperprolactinemia was
defined as blood prolactin levels >25 ng/mL in females and >20 ng/mL in males,
regardless of the presence of symptoms. RESULTS: A total of 997 patients (553
males and 444 females) were included in the current analysis. The average blood
prolactin level was 32.6 +/- 44.1 ng/mL, with higher levels among females than
males (42.9 +/- 61.3 versus 24.4 +/- 18.6, p < .001). The prevalence of
hyperprolactinemia was 44.3%, with no significant gender difference (41.9% in
females versus 46.3% in males, p = .164) but with huge variability according to
individual antipsychotic and other psychotropic medications. In the multivariate
analysis adjusted for demographic and clinical characteristics,
hyperprolactinemia was independently and positively associated with using
antipsychotic medications (OR = 2.08, 1.26-3.42, p = .004). Additionally,
previous hospitalisation, diabetes and hypothyroidism were positively associated,
whereas having primary depressive disorders was negatively associated.
CONCLUSIONS: We report a high prevalence of hyperprolactinemia among a large
sample of psychiatric patients in Saudi Arabia, which was linked to the use of
antipsychotic medications. Routine measurement of blood prolactin levels for all
patients maintained on antipsychotic agents is recommended, regardless of
symptoms.
PMID- 29334293
TI - DNA barcoding for species identification in deep-sea clams (Mollusca: Bivalvia:
Vesicomyidae).
AB - Deep-sea clams (Bivalvia: Vesicomyidae) have been found in reduced environments
over the world oceans, but taxonomy of this group remains confusing at species
and supraspecific levels due to their high-morphological similarity and
plasticity. In the present study, we collected mitochondrial COI sequences to
evaluate the utility of DNA barcoding on identifying vesicomyid species. COI
dataset identified 56 well-supported putative species/operational taxonomic units
(OTUs), approximately covering half of the extant vesicomyid species. One species
(OTU2) was first detected, and may represent a new species. Average distances
between species ranged from 1.65 to 29.64%, generally higher than average
intraspecific distances (0-1.41%) when excluding Pliocardia sp.10 cf. venusta
(average intraspecific distance 1.91%). Local barcoding gap existed in 33 of the
35 species when comparing distances of maximum interspecific and minimum
interspecific distances with two exceptions (Abyssogena southwardae and
Calyptogena rectimargo-starobogatovi). The barcode index number (BIN) system
determined 41 of the 56 species/OTUs, each with a unique BIN, indicating their
validity. Three species were found to have two BINs, together with their high
level of intraspecific variation, implying cryptic diversity within them.
Although fewer 16 S sequences were collected, similar results were obtained.
Nineteen putative species were determined and no overlap observed between intra-
and inter-specific variation. Implications of DNA barcoding for the Vesicomyidae
taxonomy were then discussed. Findings of this study will provide important
evidence for taxonomic revision in this problematic clam group, and accelerate
the discovery of new vesicomyid species in the future.
PMID- 29334294
TI - Comments on manuscript: early amniotomy after dinoprostone insert used for the
induction of labor.
PMID- 29334292
TI - Safety and effectiveness of fascial therapy in adult patients with hemophilic
arthropathy. A pilot study.
AB - BACKGROUND: The primary clinical manifestations of hemophilia are muscle and
joint bleeding. Recurrent bleeding leads to a degenerative process known as
hemophilic arthropathy. Fascial therapy is one of the most used physiotherapy
techniques today to improve joint dysfunctions and chronic pain. OBJECTIVE: To
assess the safety and efficacy of fascial therapy treatment in patients with
hemophilic arthropathy of ankle and knee. DESIGN: Non-randomized, controlled
clinical trial. INTERVENTION: Sixteen patients with hemophilia were allocated to
an experimental group or to a control group. The physiotherapy intervention was
performed through three sessions (one per week), for 60 min per session. Patients
received a physiotherapy treatment using a fascial therapy protocol for patients
with hemophilia. MAIN OUTCOME MEASURES: The joint status was evaluated using the
Hemophilia Joint Health Score; pain was assessed with the Visual Analogue Scale;
the range of movement was evaluated using a universal goniometer; the flexibility
of the hamstring muscles was assessed with the fingertip-to-floor, and the lumbar
mobility through the Schober test. RESULTS: We observed significant differences
in the experimental group for both quality of life and illness behavior. There
was no significant improvement in the joint status; however, an improvement was
noted in terms of perception of pain in the ankle. CONCLUSIONS: A physiotherapy
program based on fascial therapy is safe in patients with hemophilia. Fascial
therapy may improve joint status, pain, and mobility in patients with hemophiliac
arthropathy of the knee and ankle.
PMID- 29334296
TI - The experience of hearing loss: journey through aural rehabilitation.
PMID- 29334295
TI - Neuritin provides neuroprotection against experimental traumatic brain injury in
rats.
AB - OBJECTIVES: Traumatic brain injury (TBI) is a leading cause of death and
disability worldwide. Neuritin is a neurotrophic factor that regulates neural
growth and development. However, the role of neuritin in alleviating TBI has not
been investigated. METHODS: In this study, Sprague Dawley rats (n = 144) weighing
300 +/- 50 g were categorized into control, sham, TBI and TBI + neuritin groups.
The neurological scores and the ultrastructure of cortical neurons, apoptotic
cells and caspase-3 were measured by using Garcia scoring system, transmission
electron microscopy, terminal deoxynucleotidyl transferase-mediated dUTP nick-end
labeling, Western blot analysis and real-time RT-PCR at various time points post
TBI. CONCLUSIONS: Our findings indicated that neuritin plays a protective role in
TBI by improving neurological scores, repairing injured neurons and protecting
the cortical neurons against apoptosis through inhibition of caspase-3
expression. Further investigation of the molecular mechanisms underlying caspase
3 inhibition by neuritin will provide a research avenue for potential TBI
therapeutics.
PMID- 29334297
TI - Perceptions of older people's oral health care among nurses working in geriatric
home care.
AB - OBJECTIVES: This study investigates nurses' self-reported experiences and
perceptions of older people's oral health care using a qualitative method.
METHODS: We interviewed 10 nurses working in geriatric home care who regularly
visit and take care of older people in their homes. The interviews consisted of
semi-structured questions. The interviews were then transcribed and analysed.
RESULTS: All nurses were aware of the connection between oral health and general
health, but more detailed knowledge about oral health was lacking and confidence
in oral health care practices was limited. Many of the interviewees noted the
cleaning of removable dentures and problems related to them, but did not mention
anything about periodontal diseases. Oral health education among the nurses was
rare. The nurses reported lack of time to take care of their clients' oral
health. As possible development steps, the interviewees suggested that including
oral health care in the daily treatment plan would improve oral health care
practices. CONCLUSIONS: The nurses' lack of knowledge about oral health care and
uncertainty in oral health practices among older people are major problems in
daily geriatric home care. Oral health education and confidence in oral health
practices should be improved in both basic and on-the-job education.
PMID- 29334298
TI - Long-term effects of tungsten carbide (WC) nanoparticles in pelagic and benthic
aquatic ecosystems.
AB - As the production and usage of nanomaterials are increasing so are the concerns
related to the release of the material into nature. Tungsten carbide (WC) is
widely used for its hard metal properties, although its use, in for instance tyre
studs, may result in nano-sized particles ending up in nature. Here, we evaluate
the potential long-term exposure effects of WC nanoparticles on a pelagic
(Daphnia magna) and a benthic (Asellus aquaticus) organism. No long-term effects
were observed in the benthic system with respect to population dynamics or
ecosystem services. However, long-term exposure of D. magna resulted in increased
time to first reproduction and, if the particles were resuspended, strong effects
on survival and reproductive output. Hence, the considerable differences in acute
vs. long-term exposure studies revealed here emphasize the need for more long
term studies if we are to understand the effects of nanoparticles in natural
systems.
PMID- 29334299
TI - Mucoadhesive buccal film containing ornidazole and dexamethasone for oral ulcers:
in vitro and in vivo studies.
AB - A bilayered mucoadhesive buccal film containing a combination of ornidazole (OD)
and dexamethasone sodium phosphate (DEX) was prepared using solvent casting to
treat oral ulcers. Films were systematically evaluated in vitro to obtain the
optimum formulation. The therapeutic effects of these films were investigated in
the rabbit oral ulcer model and the in vivo release of OD and DEX in the human
oral cavity was also evaluated. The backing layer contained ethyl cellulose and
an optimal mucoadhesive layer containing both OD and DEX was produced. Films from
the optimum formulation were 0.427 +/- 0.015 mm thick, weighed 55.89 +/- 0.79 mg,
and had a surface pH of 6.34 +/- 0.01. The drug content of the optimum
formulation approximated the theoretical value with good uniformity (2.959 +/-
0.106 mg/cm2 for OD and 0.877 +/- 0.031 mg/cm2 for DEX). The formulation showed
favorable swelling characteristics and both drugs were released at >95% after 4
h. Moreover, the compound film had a statistically significant effect on mucosal
repair and reduced ulcer inflammation without stimulating the human oral mucosa.
Cmax of OD in saliva was 37.04 MUg/ml and that of DEX was 9.737 MUg/ml. Given
promising therapeutic effects, the compound film developed here could become a
local drug delivery device for treating oral ulcers.
PMID- 29334300
TI - The impact of early molecular response in children and adolescents with chronic
myeloid leukemia treated with imatinib: a single-center study from China.
AB - Chronic myeloid leukemia (CML) is rare among children and adolescents. The early
molecular response (EMR) is an important prognostic significance for adult CML
patients. This study explored the impact of EMR on the prognosis in 40 children
and adolescents with CML-CP treated with imatinib (IM). Our results showed that a
high proportion of patients failed to achieve the BCR-ABL1/ABL1 International
Scale (IS) <= 10% at 3 months. Children with a BCR-ABL1/ABL1 <= 10% at 3 months
and <1% at 6 months increased the rate of achieving complete cytogenetic response
(CCyR) and/or major molecular response (MMR) at 12 months compared to those with
BCR-ABL1/ABL1 > 10%. With a median follow-up of 42 months, patients with BCR
ABL1/ABL1 <= 10% showed a better 4-year event-free survival (EFS). In summary,
achieving BCR-ABL1/ABL1 IS <=10% at 3 months and <1% at 6 months would increase
the possibility of achieving MMR, CCyR at 12 months and had a better 4-year EFS.
EMR is a reliable prognosticator for young CML patients treated with IM.
PMID- 29334301
TI - Navigating social distance in foundational clinical encounters: Understanding
medical students' early experiences with diverse patients.
AB - BACKGROUND: Social distance between patients and physicians has been shown to
affect the quality of care that patients receive. Little is known about how
social distance between students and patients is experienced by learners during
early clinical exposures in medical school. OBJECTIVE: This study aims to explore
students' stories of experiencing social distance with patients with concordant
and discordant social characteristics as themselves, respectively, as well as
students' needs from medical curricula regarding developing social competence.
METHODS: Semi-structured interviews of medical students [n = 16] were performed,
and a post-interview survey and a visual analog scale were completed. The
interviews were audio-recorded and transcribed. The written transcripts were
coded using the constant comparison method and analyzed for emerging themes.
RESULTS: Students experience social distance with patients; yet, they are not
taught explicitly by their preceptors how to manage these experiences. Students
identified their needs for the curriculum in regard to developing social
competence and proposed various strategies and curriculum recommendations.
CONCLUSIONS: Our results support that students believe that social competence
training is important for their professional development to improve relationship
building with diverse patients. As such, it would be valuable to incorporate
student recommendations in the formation of a social competence curriculum.
PMID- 29334302
TI - miRNAs as potential regulators of mTOR pathway in renal cell carcinoma.
AB - Renal cell carcinoma (RCC) is the most commonly occurring solid cancer of the
adult kidney with the majority of RCC cases being detected accidentally. The most
aggressive subtype is clear cell RCC (ccRCC). miRNAs, a family of small noncoding
RNAs regulating gene expression have been identified as key biological
modulators. The von Hippel-Lindau pathway is one of the signaling pathways
involved in the pathophysiology of ccRCC. Another oncogenic mechanism involves
the activation of PI3K/AKT/mTOR signaling and serves as a central regulator of
cell metabolism, proliferation and survival. Several studies have described the
involvement of miRNA dysregulation in the pathogenesis and progression of ccRCC.
These molecules can be considered as potential diagnostic and prognostic
biomarkers, allowing response to therapy to be monitored.
PMID- 29334303
TI - Enteral l-arginine supplementation for prevention of necrotizing enterocolitis in
premature infants.
PMID- 29334304
TI - Switching from laparoscopic radical prostatectomy to robot assisted laparoscopic
prostatectomy: comparing oncological outcomes and complications.
AB - OBJECTIVES: To compare oncological outcomes and complication rates based on the
Clavien classification between laparoscopic radical prostatectomies (LRP) and
robot-assisted laparoscopic radical prostatectomies (RALP). MATERIAL AND METHODS:
In a prospective quality registry clinical data were consecutively entered for
544 LRP and 1081 RALP patients operated from 2003 to the end of 2012.
Complications within 90 days postoperatively were assessed according to the
Clavien classification and compared between LRP and RALP patients. Univariate and
multivariate analyses of logistic regression were used to fit oncological
outcomes and complication data. RESULTS: The mean operation time was 213 and 135
minutes in LRP and RALP patients, respectively. Pathological T3a stage (pT3a) in
the RALP group was more frequent than in the LRP group, 32.4% versus 17.8%,
respectively. For pT2 tumours, positive surgical margins (PSM) rate for LRP and
RALP, was 20.3% vs 10.6%, respectively (p < .001). In the LRP group 74 patients
(13.6%) reported 104 and in the RALP group 141 patients (13.0%) reported 177
complications (p = .75). Seventeen (3.1%) LRP patients and 15 (1.4%) RALP
patients had Clavien grade IIIb complications (p = .017). Surgical reintervention
was necessary in 14 patients (2.6%) and 17 patients (1.6%) in the LRP and RALP
group, respectively (p = .04). CONCLUSION: Switching from LRP to RALP resulted in
a much shorter operation time without compromising oncological outcome. There was
no statistically significant difference in overall complication-rates between LRP
and RALP. However, LRP patients had more serious complications and increased need
for surgical reintervention compared to RALP patients.
PMID- 29334305
TI - Twelve tips for teaching a comprehensive disease-focused course with a global
perspective: A sickle cell disease example.
AB - A disease-focused course entitled "Understanding Sickle Cell Disease: A
Biopsychosocial Approach" addressed the complex nature of SCD using patient
centered, global and interdisciplinary approaches. Sickle cell disease (SCD) is a
rare inherited blood disorder that requires multidisciplinary care. Worldwide 20
25 million individuals have SCD, which is associated with a shortened lifespan
due to many medical complications and social and behavioral health challenges.
Health care professionals often have limited knowledge of SCD as they typically
learn about it within the context of their own disciplines. This article provides
twelve tips for educators that can be used to develop a similar course on any
disease, with considerations for both low- and high-resource countries. The tips
were devised from personal experience and available literature. Through these
twelve tips, we provide a practical framework for increasing knowledge of complex
diseases like SCD using a comprehensive elective course.
PMID- 29334306
TI - Learning science as a potential new source of understanding and improvement for
continuing education and continuing professional development.
AB - Learning science is an emerging interdisciplinary field that offers educators key
insights about what happens in the brain when learning occurs. In addition to
explanations about the learning process, which includes memory and involves
different parts of the brain, learning science offers effective strategies to
inform the planning and implementation of activities and programs in continuing
education and continuing professional development. This article provides a brief
description of learning, including the three key steps of encoding, consolidation
and retrieval. The article also introduces four major learning-science
strategies, known as distributed learning, retrieval practice, interleaving, and
elaboration, which share the importance of considerable practice. Finally, the
article describes how learning science aligns with the general findings from the
most recent synthesis of systematic reviews about the effectiveness of continuing
medical education.
PMID- 29334308
TI - Neuromuscular degenerative effects of Ankaferd Blood Stopper(r) in mouse sciatic
nerve model.
AB - PURPOSE: Ankaferd Blood Stopper(r) (ABS), a licenced medicinal herbal extract, is
commonly used as an effective topical haemostatic agent. This study is designed
to investigate whether topical ABS application may cause peripheral nerve
degeneration and neuromuscular dysfunction in a mouse sciatic nerve model.
METHODS: Twenty mice were randomly divided into two groups; an ABS treated
experimental group and a saline-treated control group. Left sciatic nerves were
treated with 0.3 ml of ABS in the experimental group and 0.3 ml of sterile saline
in the control group for 5 min. Peripheral nerve degeneration and neuromuscular
dysfunction were evaluated by behavioural tests, electrophysiological analysis
and weight ratio comparison of target muscles. RESULTS: The motor function,
assessed by the sciatic function index, was significantly impaired in ABS-treated
animals as compared to the animals treated with saline. Motor coordination,
evaluated with the rotarod test, was significantly decreased (-42%) in ABS
treated animals compared to the saline-treated animals. The degree of pain,
assessed by the reaction latency to thermal stimuli (hot-plate test), was
significantly prolonged (313%) in ABS-treated mice when compared to the saline
treated mice. ABS-treated mice showed a significant reduction in motor nerve
conduction velocity (MNCV) (-52%) and the compound muscle action potential (CMAP)
(-47%); however, it significantly prolonged onset latency (23%). The
gastrocnemius muscles weight ratio of the ABS group was considerably lower than
that of the control group. CONCLUSIONS: These findings demonstrate that ABS
triggers peripheral nerve degeneration and functional impairment and, thus
promotes a deterioration of sciatic nerves.
PMID- 29334307
TI - Regorafenib regresses an imatinib-resistant recurrent gastrointestinal stromal
tumor (GIST) with a mutation in exons 11 and 17 of c-kit in a patient-derived
orthotopic xenograft (PDOX) nude mouse model.
AB - Gastrointestinal stromal tumor (GIST) with a mutation in exons 11 and 17 of c-kit
is a rare type of sarcoma. The aim of this study was to determine drug
sensitivity for a regionally-recurrent case of GIST using a patient-derived
orthotopic xenograft (PDOX) model. The PDOX model was established in the anterior
wall of the stomach. GIST PDOX models were randomized into 5 groups of 6 mice
each when the tumor volume reached 60 mm3: G1, control group; G2, imatinib group
(oral administration (p.o.), daily, for 3 weeks); G3, sunitinib group (p.o.,
daily, for 3 weeks); G4, regorafenib (p.o., daily, for 3 weeks); G5, pazopanib
(p.o., daily, for 3 weeks). All mice were sacrificed on day 22. Tumor volume was
evaluated on day 0 and day 22 by laparotomy. Body weight were measured 2 times
per week. Though regorafenib is third-line therapy for GIST, it was the most
effective drug and regressed the tumor significantly (p < 0.001). Sunitinib
suppressed tumor growth compared to the control group (p = 0.002). Imatinib,
first-line therapy for GIST, and pazopanib did not have significant efficacy
compared to the control group (p = 0.886, p = 0.766). The implications of this
result is discussed for GIST patients.
PMID- 29334309
TI - Effects of resisted sprint training on sprinting ability and change of direction
speed in professional soccer players.
AB - Resisted sprint training consists of performing overloaded sprints, which may
produce greater effects than traditional sprint training. We compared a resisted
sprint training with overload control versus an unresisted sprint training
program on performance in soccer players. Eighteen elite athletes were randomly
assigned to resisted (RST) or unresisted sprint training protocol (UR). Before
and after a 6-week training period, sprinting ability, change of direction speed
(COD), vertical jumps (SJ and CMJ), mean power (MP) and mean propulsive power
(MPP) at distinct loads were assessed. Both groups improved sprinting ability at
all distances evaluated (5m: UR = 8%, RST = 7%; 10m: UR = 5%, RST = 5%; 15m: UR =
4%, RST = 4%; 20m: UR = 3%, RST = 3%; 25m: UR = 2%, RST = 3%;), COD (UR = 6%; RST
= 6%), SJ (UR = 15%; RST = 13%) and CMJ (UR = 15%; RST = 15%). Additionally, both
groups increased MP and MPP at all loads evaluated. The between-group magnitude
based inference analysis demonstrated comparable improvement ("trivial" effect)
in all variables tested. Finally, our findings support the effectiveness of a
short-term training program involving squat jump exercise plus sprinting
exercises to improve the performance of soccer players.
PMID- 29334310
TI - Dendritic polyglycerol nanoparticles show charge dependent bio-distribution in
early human placental explants and reduce hCG secretion.
AB - A thorough understanding of nanoparticle bio-distribution at the feto-maternal
interface will be a prerequisite for their diagnostic or therapeutic application
in women of childbearing age and for teratologic risk assessment. Therefore, the
tissue interaction of biocompatible dendritic polyglycerol nanoparticles (dPG
NPs) with first- trimester human placental explants were analyzed and compared to
less sophisticated trophoblast-cell based models. First-trimester human placental
explants, BeWo cells and primary trophoblast cells from human term placenta were
exposed to fluorescence labeled, ~5 nm dPG-NPs, with differently charged
surfaces, at concentrations of 1 uM and 10 nM, for 6 and 24 h. Accumulation of
dPGs was visualized by fluorescence microscopy. To assess the impact of dPG-NP on
trophoblast integrity and endocrine function, LDH, and hCG releases were
measured. A dose- and charge-dependent accumulation of dPG-NPs was observed at
the early placental barrier and in cell lines, with positive dPG-NP-surface
causing deposits even in the mesenchymal core of the placental villi. No signs of
plasma membrane damage could be detected. After 24 h we observed a significant
reduction of hCG secretion in placental explants, without significant changes in
trophoblast apoptosis, at low concentrations of charged dPG-NPs. In conclusion,
dPG-NP's surface charge substantially influences their bio-distribution at the
feto-maternal interface, with positive charge facilitating trans-trophoblast
passage, and in contrast to more artificial models, the first-trimester placental
explant culture model reveals potentially hazardous influences of charged dPG-NPs
on early placental physiology.
PMID- 29334311
TI - The surface chemistry determines the spatio-temporal interaction dynamics of
quantum dots in atherosclerotic lesions.
AB - AIM: To optimize the design of nanoparticles for diagnosis or therapy of vascular
diseases, it is mandatory to characterize the determinants of nano-bio
interactions in vascular lesions. MATERIALS & METHODS: Using ex vivo and in vivo
microscopy, we analyzed the interactive behavior of quantum dots with different
surface functionalizations in atherosclerotic lesions of ApoE-deficient mice.
RESULTS: We demonstrate that quantum dots with different surface
functionalizations exhibit specific interactive behaviors with distinct molecular
and cellular components of the injured vessel wall. Moreover, we show a role for
fibrinogen in the regulation of the spatio-temporal interaction dynamics in
atherosclerotic lesions. CONCLUSION: Our findings emphasize the relevance of
surface chemistry-driven nano-bio interactions on the differential in vivo
behavior of nanoparticles in diseased tissue.
PMID- 29334312
TI - Targeting of phospho-eIF4E by homoharringtonine eradicates a distinct subset of
human acute myeloid leukemia.
AB - More than half of the patients with acute myeloid leukemia (AML) fail to achieve
long-term disease-free survival with current therapies and novel therapeutic
strategies are urgently needed. The effects of homoharringtonine (HHT) on the
growth of AML cell lines and primary leukemia cells were examined using MTT,
colony formation assay. The effects of HHT on both eukaryotic translation
initiation factor 4E (eIF4E) and phospho-eIF4E(p-eIF4E) were examined through
western blot and immunofluorescence staining. HHT selectively reduced levels of p
eIF4E and its downstream oncoprotein Mcl-1, and potently inhibited in vitro and
in vivo the growth of a distinct subset of AML cells and primary leukemia cells
expressing high level of p-eIF4E through apoptosis. Our findings suggest that HHT
might be a first-in-class p-eIF4E-targeted drug and offer a novel therapeutic
option for AML patients expressing high level of p-eIF4E.
PMID- 29334314
TI - On the intrinsic constraint of bacterial growth rate: M. tuberculosis's view of
the protein translation capacity.
AB - In nature, the maximal growth rates vary widely among different bacteria species.
Fast-growing bacteria species such as Escherichia coli can have a shortest
generation time of 20 min. Slow-growing bacteria species are perhaps best known
for Mycobacterium tuberculosis, a human pathogen with a generation time being no
less than 16 h. Despite of the significant progress made on understanding the
pathogenesis of M. tuberculosis, we know little on the origin of its intriguingly
slow growth. From a global view, the intrinsic constraint of the maximal growth
rate of bacteria remains to be a fundamental question in microbiology. In this
review, we analyze and discuss this issue from the angle of protein translation
capacity, which is the major demand for cell growth. Based on quantitative
analysis, we propose four parameters: rRNA chain elongation rate, abundance of
RNA polymerase engaged in rRNA synthesis, polypeptide chain elongation rate, and
active ribosome fraction, which potentially limit the maximal growth rate of
bacteria. We further discuss the relation of these parameters with the growth
rate for M. tuberculosis as well as other bacterial species. We highlight future
comprehensive investigation of these parameters for different bacteria species to
understand how bacteria set their own specific growth rates.
PMID- 29334313
TI - Pneumonia infection in mice reveals the involvement of the feoA gene in the
pathogenesis of Acinetobacter baumannii.
AB - Acinetobacter baumannii has emerged in the last decade as an important nosocomial
pathogen. To identify genes involved in the course of a pneumonia infection, gene
expression profiles were obtained from A. baumannii ATCC 17978 grown in mouse
infected lungs and in culture medium. Gene expression analysis allowed us to
determine a gene, the A1S_0242 gene (feoA), over-expressed during the pneumonia
infection. In the present work, we evaluate the role of this gene, involved in
iron uptake. The inactivation of the A1S_0242 gene resulted in an increase
susceptibility to oxidative stress and a decrease in biofilm formation, in
adherence to A549 cells and in fitness. In addition, infection of G. mellonella
and pneumonia in mice showed that the virulence of the Delta0242 mutant was
significantly attenuated. Data presented in this work indicated that the A1S_0242
gene from A. baumannii ATCC 17978 strain plays a role in fitness, adhesion,
biofilm formation, growth, and, definitively, in virulence. Taken together, these
observations show the implication of the feoA gene plays in the pathogenesis of
A. baumannii and highlight its value as a potential therapeutic target.
PMID- 29334315
TI - Interplay between p53 and Ink4c in spermatogenesis and fertility.
AB - The tumor suppressor p53, and the cyclin-dependent kinase inhibitor Ink4c, have
been both implicated in spermatogenesis control. Both p53-/- and Ink4c-/- single
knockout male mice are fertile, despite testicular hypertrophy, Leydig cell
differentiation defect, and increased sperm count in Ink4c-/- males. To
investigate their collaborative roles, we studied p53-/- Ink4c-/- dual knockout
animals, and found that male p53-/- Ink4c-/- mice have profoundly reduced
fertility. Dual knockout male mice show a marked decrease in sperm count,
abnormal sperm morphology and motility, prolongation of spermatozoa proliferation
and delay of meiosis entry, and accumulation of DNA damage. Genetic studies
showed that the effects of p53 loss on fertility are independent of its
downstream effector Cdkn1a. Absence of p53 also partially reverses the
hyperplasia seen upon Ink4c loss, and normalizes the Leydig cell differentiation
defect. These results implicate p53 in mitigating both the delayed entry into
meiosis and the secondary apoptotic response that occur in the absence of Ink4c.
We conclude that the cell cycle genes p53 and Ink4c collaborate in sperm cell
development and differentiation, and may be important candidates to investigate
in human male infertility conditions.
PMID- 29334316
TI - Potential therapeutic and economic value of risk-stratified treatment as initial
treatment of multiple myeloma in Europe.
AB - Biomarkers associated with prognosis in multiple myeloma (MM) can be used to
stratify patients into risk categories. An attractive alternative to uniform
treatment (UT), risk-stratified treatment (RST) is proposed where high-risk
patients receive bortezomib-based regimens while standard-risk patients receive
alternative less costly regimens. An early Markov-type decision analytic model
evaluated the potential therapeutic and economic value of different RST
strategies compared with UT in MM patients in key European countries. Results
suggest RST strategies were both cheaper and more effective than UT across all
countries, with the molecular marker-only strategy RST-SKY92 producing maximum
health gains (0.031-0.039 QALYs). The conclusions remained consistent in the
univariate sensitivity analyses. These findings should encourage stakeholders to
support the adoption of RST approaches in MM.
PMID- 29334317
TI - Fluctuation - a common but neglected pattern of physical activity behaviour: An
exploratory review of studies in recent 20 years.
AB - BACKGROUND: Regular physical activity (PA) is beneficial for physical and
psychological well-being, yet many people do not achieve these health benefits
due to irregular PA participation which is also known as fluctuation. Limited
attention has been given to the phenomenon of fluctuation in the PA behaviour
literature. OBJECTIVE: The aim of this review was to explore and to map
definitions, measurements, behavioural evidence, and factors related to PA
fluctuation. METHODS: Eligible studies were initially identified by a systematic
search of articles conducted in four databases: Scopus, PubMed, PsycINFO, and
SPORTDiscus between January 1996 and March 2016. Inclusion and exclusion criteria
were set to check the eligibility of all articles. Additional articles were
included by manual searching and expert recommendation. RESULTS: Fifteen articles
were finally included. Definitions of fluctuation are understood from two
perspectives, either as a stage in the process of behaviour change, or as a
particular PA phenomenon consisting of lapse and readoption. Common features were
extracted: behavioural irregularity, high risk of drop-out, intention and
readiness for PA, low automaticity, and limited self-regulation. Furthermore,
fluctuation identification was summarised in three approaches such as stage
algorithm, self-identified PA lapse and readoption, and prospective within-person
variation in meeting the PA guidelines. Regarding the empirical evidence, this
review found that people in PA fluctuation were significantly distinct from those
in preparation and maintenance of PA behavioural performance, as well as distinct
in psychosocial features. CONCLUSIONS: Notwithstanding the limitations, this
review has provided valuable insight into the phenomenon of PA fluctuation.
PMID- 29334318
TI - Molecular dynamics perspective on the thermal stability of mandelate racemase.
AB - Mandelate racemase from Pseudomonas putida is a promising candidate for the
dynamic kinetic resolution of alpha-hydroxy carboxylic acids. In the present
study, the thermal stability of mandelate racemase was investigated through
molecular dynamics simulations in the temperature range of 303-363 K, which can
guide the design of mandelate racemase with higher stability. The basic features
such as radius of gyration, surface accessibility, and secondary structure
content suggested the instability of mandelate racemase at high temperatures.
With increase in temperature, alpha-helix content reduced significantly,
especially the alpha-helices exposed to the environment. At the simulation time
scale considered, intra-protein hydrogen bonds, hydrogen bonds between protein
and water decreased at 363 K, while the number of salt-bridges increased. The
long-distance networks remarkably changed at 363 K. A considerable number of long
lived (percentage existence time higher than 90%) hydrogen bonds and Calpha
contacts were lost. Root mean square fluctuation analysis revealed regions with
high fluctuation, which should be helpful in the reengineering of mandelate
racemase for enhanced thermal stability.
PMID- 29334319
TI - Effect of Porphyromonas gingivalis infection in the placenta and umbilical cord
in pregnant mice with low birth weight.
AB - OBJECTIVE: Growing evidence indicates an association between periodontitis and
delivery outcome; however, the mechanism is unclear. This study aimed to
investigate the influence of Porphyromonas gingivalis (Pg) infection on delivery
outcome in mice. MATERIALS AND METHODS: Bacteremia was induced in pregnant
Slc:ICR mice (8 weeks old) by intravenous injection of Pg. Mice were randomly
divided into a control group (CO), and those receiving Pg injection at
gestational day 1 (GD1), gestational day 15 (GD15) or every day (ED). Delivery
outcome, Pg infection, and gene expression in the placenta and umbilical cord
were evaluated. RESULTS: Birth weight was lower in the ED and GD15 groups than in
the CO group. A remarkable increase in anti-Pg IgG antibody was observed in the
ED and GD1 groups, although Pg was not detected in the placenta or umbilical
cord. mRNA expression of Tnfalpha and Il6 in the placenta, and Hif1alpha in the
umbilical cord, was significantly increased in the ED group. Microarray analysis
of the umbilical cord revealed increased expression of several genes including
Orm1, Mgl2, Rps6ka3 and Trim15 in the ED group. CONCLUSIONS: Pg infection during
the third trimester caused low birth weight and inflammation in the placenta and
umbilical cord.
PMID- 29334320
TI - Human dopamine transporter: the first implementation of a combined in silico/in
vitro approach revealing the substrate and inhibitor specificities.
AB - Parkinson's disease (PD) is characterized by the loss of dopamine-generating
neurons in the substantia nigra and corpus striatum. Current treatments alleviate
PD symptoms rather than exerting neuroprotective effect on dopaminergic neurons.
New drugs targeting the dopaminergic neurons by specific uptake through the human
dopamine transporter (hDAT) could represent a viable strategy for establishing
selective neuroprotection. Molecules able to increase the bioactive amount of
extracellular dopamine, thereby enhancing and compensating a loss of dopaminergic
neurotransmission, and to exert neuroprotective response because of their
accumulation in the cytoplasm, are required. By means of homology modeling,
molecular docking, and molecular dynamics simulations, we have generated 3D
structure models of hDAT in complex with substrate and inhibitors. Our results
clearly reveal differences in binding affinity of these compounds to the hDAT in
the open and closed conformations, critical for future drug design. The
established in silico approach allowed the identification of promising substrate
compounds that were subsequently analyzed for their efficiency in inhibiting hDAT
dependent fluorescent substrate uptake, through in vitro live cell imaging
experiments. Taken together, our work presents the first implementation of a
combined in silico/in vitro approach enabling the selection of promising
dopaminergic neuron-specific substrates.
PMID- 29334321
TI - Biosynthesis of galactomannans found in filamentous fungi belonging to
Pezizomycotina.
AB - The galactomannans (GMs) that are produced by filamentous fungi belonging to
Pezizomycotina, many of which are pathogenic for animals and plants, are
polysaccharides consisting of alpha-(1->2)-/alpha-(1->6)-mannosyl and beta-(1->5)
/beta-(1->6)-galactofuranosyl residues. GMs are located at the outermost layer of
the cell wall. When a pathogenic fungus infects a host, its cell surface must be
in contact with the host. The GMs on the cell surface may be involved in the
infection mechanism of a pathogenic fungus or the defense mechanism of a host.
There are two types of GMs in filamentous fungi, fungal-type galactomannans and O
mannose type galactomannans. Recent biochemical and genetic advances have
facilitated a better understanding of the biosynthesis of both types. This review
summarizes our current information on their biosynthesis.
PMID- 29334322
TI - Plasma brain-derived neurotrophic factor (pBDNF) and executive dysfunctions in
patients with major depressive disorder.
AB - OBJECTIVES: Executive dysfunctions are frequently seen in patients with major
depressive disorder (MDD) and normalise in many cases during effective
antidepressant therapy. This study investigated whether a normalisation of
executive dysfunctions during antidepressant treatment correlates with or can be
predicted by clinical parameters or levels of brain-derived neurotrophic factor
(BDNF). METHODS: In 110 MDD patients with executive dysfunctions (percentile
<16), executive functions and plasma BDNF levels were analysed at baseline, and
days 14 and 56 of an antidepressant treatment. BDNF exon IV and P11 methylation
status was studied at baseline. RESULTS: Eighty patients (73%) experienced a
normalisation of executive dysfunctions, while 30 (27%) suffered from persistent
dysfunctions until day 56. Patients with persistent dysfunctions had
significantly higher HAMD scores at days 14 and 56, and lower plasma BDNF levels
at each time point than patients with a normalisation of dysfunctions (F1= 10.18;
P = 0.002). This was seen for verbal fluency, but not processing speed. BDNF exon
IV and p11 promoter methylation was not associated with test performance.
CONCLUSIONS: Our results corroborate a concomitant amelioration of executive
dysfunctions with successful antidepressant therapy and support a role of BDNF in
the neural mechanisms underlying the normalisation of executive dysfunctions in
MDD. ClinicalTrials.gov number: NCT00974155; EudraCT: 2008-008280-96.
PMID- 29334323
TI - Development of functional agricultural products utilizing the new health claim
labeling system in Japan.
AB - In April 2015, Consumer Affairs Agency of Japan launched a new food labeling
system known as "Foods with Function Claims (FFC)." Under this system, the food
industry independently evaluates scientific evidence on foods and describes their
functional properties. As of May 23, 2017, 1023 FFC containing 8 fresh foods have
been launched. Meanwhile, to clarify the health-promoting effects of agricultural
products, National Agriculture and Food Research Organization (NARO) implemented
the "Research Project on Development of Agricultural Products" and demonstrated
the risk reduction of osteoporosis of beta-cryptoxanthin rich Satsuma mandarins
and the anti-allergic effect of the O-methylated catechin rich tea cultivar
Benifuuki. These foods were subsequently released as FFC. Moreover, NARO
elucidated the health-promoting effects of various functional agricultural
products (beta-glucan rich barley, beta-conglycinin rich soybean, quercetin rich
onion, etc.) and a healthy boxed lunch. This review focuses on new food labeling
system or research examining functional aspects of agricultural products.
PMID- 29334324
TI - The rite of passage of becoming a humanitarian health worker: experiences of
retention in Sweden.
AB - BACKGROUND: Low retention of humanitarian workers poses constraints on
humanitarian organisations' capacity to respond effectively to disasters.
Research has focused on reasons for humanitarian workers leaving the sector, but
little is known about the factors that can elucidate long-term commitment.
OBJECTIVE: To understand what motivates and supports experienced humanitarian
health workers to remain in the sector. METHODS: Semi-structured interviews were
conducted with 10 experienced nurses who had been on at least three field
missions with Medecins Sans Frontieres Sweden. Interviews explored factors
influencing the decision to go on missions, how nurses were supported and how
they looked back on those experiences. Transcripts were analysed through content
analysis informed by van Gennep's concept of 'Rite of Passage', combined with
elements of the self-determination theory. RESULTS: The findings indicate that
their motivations and how nurses thought of themselves, as individuals and
professionals, changed over time. For initiation and continued engagement in
humanitarian work, participants were motivated by several personal and
professional ambitions, as well as altruistic principles of helping others. When
starting their first humanitarian missions, nurses felt vulnerable and had low
self-esteem. However, through experiencing feelings of autonomy, competence and
relatedness during missions, they underwent a process of change and gradually
adjusted to new roles as humanitarian health workers. Reintegration in their home
community, while maintaining the new roles and skills from the missions, proved
very challenging. They individually found their own ways of overcoming the lack
of social support they experienced after missions in order to sustain their
continuation in the sector. CONCLUSIONS: The findings highlight the importance of
social environments that facilitate and support the adjustment of individuals
during and after field missions. Learning from positive examples, such as nurses
with several years of experience, can strengthen strategies of retention, which
can ultimately improve the delivery of humanitarian assistance.
PMID- 29334325
TI - Concurrent validity and reliability of torso-worn inertial measurement unit for
jump power and height estimation.
AB - The purpose of the present study was to evaluate the concurrent validity and test
retest repeatability of torso-worn IMU-derived power and jump height in a counter
movement jump test. Twenty-seven healthy recreationally active males (age, 21.9
[SD 2.0] y, height, 1.76 [0.7] m, mass, 73.7 [10.3] kg) wore an IMU and completed
three counter-movement jumps a week apart. A force platform and a 3D motion
analysis system were used to concurrently measure the jumps and subsequently
derive power and jump height (based on take-off velocity and flight time). The
IMU significantly overestimated power (mean difference = 7.3 W/kg; P < 0.001)
compared to force-platform-derived power but good correspondence between methods
was observed (Intra-class correlation coefficient [ICC] = 0.69). IMU-derived
power exhibited good reliability (ICC = 0.67). Velocity-derived jump heights
exhibited poorer concurrent validity (ICC = 0.72 to 0.78) and repeatability (ICC
= 0.68) than flight-time-derived jump heights, which exhibited excellent validity
(ICC = 0.93 to 0.96) and reliability (ICC = 0.91). Since jump height and power
are closely related, and flight-time-derived jump height exhibits excellent
concurrent validity and reliability, flight-time-derived jump height could
provide a more desirable measure compared to power when assessing athletic
performance in a counter-movement jump with IMUs.
PMID- 29334326
TI - Predicting the dopamine D2 receptor occupancy of ropinirole in rats using
positron emission tomography and pharmacokinetic-pharmacodynamic modeling.
AB - 1. The purpose of this study was to measure dopamine D2/3 receptor occupancy (RO)
as a marker of the clinical efficacy of ropinirole in rats via positron emission
tomography (PET) using 18F-fallypride as the radiotracer and to explore the
relationship between dopamine RO and the plasma concentration of ropinirole via
pharmacokinetic-pharmacodynamic modeling. 2. Plasma was collected from 16 rats
treated with one of four doses of ropinirole. For the time-dependent study, the
data of 16 rats in the 15 mg/kg dose group at four time points were averaged, and
another 24 rats were divided into three dose groups (5 mg/kg, 30 mg/kg and 60
mg/kg) for the dose-dependent study; the animals were assessed via 18F-fallypride
PET scans. The correlation between dopamine RO and the ropinirole plasma
concentration was investigated, and a pharmacokinetic-pharmacodynamic (PK-PD)
model was established with WinNonlin 6.3 software. Both the plasma concentration
and the binding potential changed in a time- and dose-dependent manner, and the
plasma concentration that induces 50% RO (EC50) as calculated by the PK-PD model
was 1391 ng/mL. 3. 18F-fallypride appeared to be a suitable radiotracer for
ropinirole imaging, and its binding to the dopamine D2 receptor has time- and
concentration-dependent characteristics. A theory-based PK-PD model was developed
to describe the relationship between the plasma ropinirole concentration and RO,
providing a methodological foundation for noninvasive and in vivo clinical
evaluations of ropinirole treatment.
PMID- 29334327
TI - Migration of a Kirschner wire into the spinal cord: A case report and literature
review.
AB - CONTEXT: A Kirschner wire (K-wire) is a stainless steel pin with at least one
sharpened tip that is mainly used for the internal fixation of bone fractures.
While some cases of K-wire dislocation and migration have been reported as
complications after fracture surgery, the intraspinal migration of a K-wire is
rare. Herein, we report a case in which a K-wire used for sternal fixation 7
years earlier migrated into the spinal canal. FINDINGS: A 68-year-old male
suddenly sustained severe radiating pain and numbness in his left upper
extremity, and walked to our hospital. He had mild weakness in the left wrist
extensor muscles and the left extensor digitorum. CT-myelography revealed a K
wire penetrating into the spinal cord at C5-6. There was no injury of the
trachea, esophagus, or blood vessels. The patient had a history of surgical
infection after cardiovascular surgery seven years before, and had undergone
surgical debridement and sternum fixation with two K-wires. One K-wire had
broken, and part of it migrated upward. Using an anterior approach, we detected
the tip of K-wire below the left sternocleidomastoid muscle. We cut the K-wire
into 1 to 2-cm pieces and removed it piece by piece. His postoperative course was
uneventful and the symptoms improved markedly after the surgery. CONCLUSION: This
is the first report of a K-wire that had been used for sternal fixation migrating
into the spinal cord. This case illustrates that although rare, it is possible
for a K-wire to migrate upward after sternal fixation.
PMID- 29334328
TI - Different durations within the method of best practice affect the parameters of
the speed-duration relationship.
AB - The aim of the study was to determine whether estimates of the speed-duration
relationship are affected using different time-trial (TT) field-based testing
protocols, where exhaustive times were located within the generally recommended
durations of 2-15 min. Ten triathletes (mean +/- SD age: 31.0 +/- 5.7 years;
height: 1.81 +/- 0.05 m; body mass: 76.5 +/- 6.8 kg) performed two randomly
assigned field tests to determine critical speed (CS) and the total distance
covered above CS (D). CS and D were obtained using two different protocols
comprising three TT that were interspersed by 60 min passive rest. The TTs were
12, 7, and 3 min in Protocol I and 10, 5, and 2 min in Protocol II. A linear
relationship of speed vs. the inverse of time (s = D * 1/t + CS) was used to
determine parameter estimates. Significant differences were found for CS (p =
0.026), but not for D (p = 0.123). The effect size for CS (d = 0.305) was
considered small, while that for D was considered moderate (d = 0.742). CS was
significantly correlated between protocols (r = 0.934; p < 0.001), however, no
correlation was found for D (r = 0.053; p = 0.884). The 95% limits of agreement
were +/-0.28m s-1 and +/-73.9 m for CS and D, respectively. These findings
demonstrate that the choice of exhaustive times within commonly accepted
durations results in different estimates of CS and D, and thus protocols cannot
be used interchangeably. The use of a consistent protocol is therefore
recommended, when investigating or monitoring the speed-duration relationship
estimates in well-trained athletes.
PMID- 29334329
TI - Predictive value of metabolic syndrome definitions in patients with myocardial
infarction with ST segment elevation - are they all the same?
AB - OBJECTIVES: We sought to determine the predictive power of metabolic syndrome
(MS) definitions on the prognosis in patients with myocardial infarction with ST
segment elevation (STEMI). METHODS: We prospectively included 507 patients with
STEMI who were admitted for primary percutaneous coronary intervention and could
be identified for MS using the AHA-NHLBI, NCEP-ATP III and IDF definitions. After
applying these criteria, we divided the group in patients with MS and without MS;
we compared baseline characteristics, clinical findings and outcomes among these
patients. RESULTS: The prevalence of MS was lowest with the NCEP-ATP III
definition (37.87%), followed by the AHA-NHLBI definition (42.80%) and highest
when using the IDF definition (44.38%). During follow-up, the occurrence of new
myocardial infarction and new revascularization was significantly higher in
patients with MS. Only in a group of patients with MS according to the NCEP-ATP
III definition, a higher number of strokes were recorded. Multivariate analysis
shows that MS according to the NCEP-ATP III definition was an independent
predictor for MACE (OR 1.830, 95% CI 1.238-2.704, p = .002) but not for
mortality. CONCLUSION: Metabolic syndrome according to the NCEP-ATP III
definition was associated with increased risk of the development of new
cardiovascular events among the patients with STEMI.
PMID- 29334330
TI - The presence of free d-aspartate in marine macroalgae is restricted to the
Sargassaceae family.
AB - The presence of d-aspartate (d-Asp), a biologically rare amino acid, was
evaluated in 38 species of marine macroalgae (seaweeds). Despite the ubiquitous
presence of free l-Asp, free d-Asp was detected in only 5 species belonging to
the Sargassaceae family of class Phaeophyceae (brown algae) but not in any
species of the phyla Chlorophyta (green algae) and Rhodophyta (red algae). All
other members of Phaeophyceae, including 3 species classified into the section
Teretia of Sargassaceae did not contain d-Asp. These results indicate that the
presence of free d-Asp in marine macroalgae is restricted only to the
Sargassaceae family, excluding the species in the section Teretia.
PMID- 29334331
TI - Transport mobility 5 years after stroke in an urban setting.
AB - Background People after stroke may have residual problems with mobility that can
affect their independence and mode of transport. However, there is limited
knowledge about transport mobility several years after stroke. Objective The
objective was to survey the outdoor mobility and transportation in an urban
setting five years post-stroke. Method This cross-sectional study was based on a
mail survey focusing on long-term consequences after stroke. The survey comprises
a set of self-evaluated questionnaires and was sent to 457 persons, of whom 281
responded (61.5%). From the survey, items regarding transportation and mobility
were selected and analyzed. Results A high level of mobility function was
reported with regard to outdoor mobility and different modes of transport.
However, one-fifth still reported problems with outdoor mobility and mode of
transport. Some perceived barriers were reported, predominantly mobility aspects
such as transfer to/from, and getting on/off specific transportation mode/s. The
respondents reported some communication problems and cognitive impairments, but
these were not reported as prominent barriers when using public transport. A
total of 67% were active drivers and were more often men (p = 0.002), younger (p
<= 0.001), and were less dependent at discharge from the acute hospital (p <=
0.001). Conclusions Five years post-stroke, mobility problems were the dominant
barrier reported when using transport modes. Individualized transport training is
needed during rehabilitation to increase possibility to participate.
Infrastructure and transportation planning should focus on older, women, and
people with impairments to be able to facilitate the use of public transport and
mobility.
PMID- 29334332
TI - Quantifying lower extremity and trunk function for dressing in stroke patients: a
retrospective observational study.
AB - Background Dressing performance relates strongly with balance function, and it is
mainly influenced by the motor functions of the affected and unaffected lower
extremity and trunk function in stroke patients. For the remedial approach to be
effective, ascertaining the degree of function needed in the affected and
unaffected lower extremities and trunk to achieve balance function requisite for
dressing is necessary. Objectives This study aimed to elucidate standards of
lower extremity and trunk function necessary for stroke patients to gain balance
requisite for dressing. Methods The study included 105 first-time stroke
patients, who were classified by Berg Balance Score >=44 or not and >=32 or not
which are previously reported standard indicators for independent and supervision
level in dressing. Receiver operating characteristic curves were determined for
the stroke impairment assessment item of sensory and motor function of affected
lower extremity, abdominal muscle strength, and knee extension muscle strength.
Results Area under the curve was >=0.7 for all variables. In BBS 44-point
analyses, the calculated cut-off values were 4 points for SIAS hip flexion, 4
points for SIAS knee extension, 2 points for SIAS foot pat on the affected side,
3 points for SIAS tactile and position sensation of the affected lower extremity,
3 points for SIAS abdominal muscle strength, and 3 points for SIAS knee extension
muscle strength on the unaffected side. Conclusions These cut-off values can be
used as targets for motor functions, when using the remedial approach for
achieving dressing independence.
PMID- 29334333
TI - Are people at high risk for diabetes visiting health facility for confirmation of
diagnosis? A population-based study from rural India.
AB - BACKGROUND: India is witnessing a rising burden of type 2 diabetes mellitus.
India's National Programme for Prevention and Control of Diabetes, Cancer,
Cardiovascular diseases and Stroke recommends population-based screening and
referral to primary health centre for diagnosis confirmation and treatment
initiation. However, little is known about uptake of confirmatory tests among
screen positives. OBJECTIVE: To estimate the uptake of confirmatory tests and
identify the reasons for not undergoing confirmation by those at high risk for
developing diabetes. METHODS: We analysed data collected under project UDAY, a
comprehensive diabetes and hypertension prevention and management programme,
being implemented in rural Andhra Pradesh, India. Under UDAY, population-based
screening for diabetes was carried out by project health workers using a diabetes
risk score and capillary blood glucose test. Participants at high risk for
diabetes were asked to undergo confirmatory tests. On follow-up visit, health
workers assessed if the participant had undergone confirmation and ask for
reasons if not so. RESULTS: Of the 35,475 eligible adults screened between April
2015 and August 2016, 10,960 (31%) were determined to be at high risk. Among
those at high risk, 9670 (88%) were followed up, and of those, only 616 (6%)
underwent confirmation. Of those who underwent confirmation, 'lack of symptoms of
diabetes warranting visit to health facility' (52%) and 'being at high risk was
not necessary enough to visit' (41%) were the most commonly reported reasons for
non-confirmation. Inconvenient facility time (4.4%), no nearby facility (3.2%),
un-affordability (2.2%) and long waiting time (1.6%) were the common health
system-related factors that affected the uptake of the confirmatory test.
CONCLUSION: Confirmation of diabetes was abysmally low in the study population.
Low uptake of the confirmatory test might be due to low 'risk perception'. The
uptake can be increased by improving the population risk perception through
individual and/or community-focused risk communication interventions.
PMID- 29334334
TI - Mortality after endovascular treatment of infrarenal abdominal aortic aneurysms -
the newer the better?
AB - Although endovascular repair of infrarenal abdominal aortic aneurysms (EVAR)
presents a delicate alternative treatment for abdominal aortic aneurysms (AAA)
with lower perioperative mortality, its long-term efficacy remains a matter of
concern. The purpose of this study was to evaluate the currently reported
mortality evidence after EVAR and to examine the possible effect of aneurysm
status and the study period on mortality rates. The PubMed and Cochrane
bibliographical databases were thoroughly searched for studies reporting on more
than 1 000 patients with non-ruptured or ruptured infrarenal AAA, treated with
EVAR from August 1991 to September 2016. A total of 10 910 titles/abstracts were
retrieved and 121 studies were deemed relevant. Twenty-six studies met the
inclusion criteria and reported on 354 500 patients with a mean age of 74.6
years. Almost all of the studies referred to elective EVAR and the mean aneurysm
size was 5.58 cm. The most common early complication for elective EVAR was
perioperative bleeding (1.9 %), whereas hospital-acquired pneumonia was a major
concern in urgent EVAR (28.5 %). Conversion rate to open surgery was 1.2 %. The
30-day all-cause mortality rate was 4.84 % (1.7 % for non- ruptured aneurysms,
33.8 % for ruptured aneurysms).The overall all-cause late mortality in a mean
follow-up period of 23.8 months was 19.1 %. The aneurysm-related late mortality
rate was 3.4 %. With respect to the time period of patient enrollment, studies
reporting on patients recruited before 2006 were found to face more secondary
complications and higher late mortality rates than patients enrolled after
2005.The endovascular treatment of large and anatomically suitable infrarenal AAA
in selected patients remains a safe alternative to open repair. Our findings
demonstrate that newer studies show better long-term outcomes than the older
ones, proposing a possible improvement of EVAR techniques and perioperative care
and providing encouraging evidence for a wider application of EVAR.
PMID- 29334335
TI - Simultaneous formation of polycyclic aromatic hydrocarbons (PAHs) and
heterocyclic aromatic amines (HCAs) in gas-grilled beef satay at different
temperatures.
AB - This study investigated the simultaneous formation of polycyclic aromatic
hydrocarbons (PAHs) and heterocyclic aromatic amines (HCAs) in gas-grilled beef
satay at different temperatures (150, 200, 250, 300, and 350 degrees C). Solid
phase extraction (SPE) was used for sample clean-up. Fifteen PAHs were determined
using high performance liquid chromatography with fluorescence detection (HPLC
FLD) and nine HCAs were quantified using liquid chromatography tandem-mass
spectrometry (LC-MS/MS) with a gradient programme. The lowest significantly
concentrations of PAHs and HCAs were generated at 150 degrees C; the formation of
PAHs and HCAs simultaneously increased with temperatures. Benzo[a]pyrene was
detected in all samples and increased markedly at 300 and 350 degrees C. The sums
of 4 PAHs (PAH4) in marinated beef satay at 300 and 350 degrees C exceeded the
maximum level in Commission Regulation (EU) 2015/1125. Significant reductions of
polar and non-polar HCAs (except PhIP) were found in marinated beef satay across
all temperatures. Overall, PAHs and HCAs showed opposite trends of formation in
beef satay with marination.
PMID- 29334336
TI - Engineering mechanical microenvironment of macrophage and its biomedical
applications.
AB - Macrophages are the most plastic cells in the hematopoietic system and can be
widely found in almost all tissues. Recently studies have shown that mechanical
cues (e.g., matrix stiffness and stress/strain) can significantly affect
macrophage behaviors. Although existing reviews on the physical and mechanical
cues that regulate the macrophage's phenotype are available, engineering
mechanical microenvironment of macrophages in vitro as well as a comprehensive
overview and prospects for their biomedical applications (e.g., tissue
engineering and immunotherapy) has yet to be summarized. Thus, this review
provides an overview on the existing methods for engineering mechanical
microenvironment of macrophages in vitro and then a section on their biomedical
applications and further perspectives are presented.
PMID- 29334337
TI - Durable responses in refractory autoimmune hemolytic anemia with alemtuzumab.
AB - Autoimmune hemolytic anemia occurs due to an interaction of IgG antibodies with
protein antigens expressed on red blood corpuscles. Glucocorticoids are the
mainstay of treatment for autoimmune hemolytic anemia. For patients not
responding to initial therapy, other agents such as rituximab, immunosuppressive
therapy, or splenectomy are considered. When refractory to these treatment
options, alemtuzumab is an alternative agent. However, long-term outcomes of
patients supporting its use are lacking. We present three patients with
refractory autoimmune hemolytic anemia treated with alemtuzumab.
PMID- 29334338
TI - At-home genital nerve stimulation for individuals with SCI and neurogenic
detrusor overactivity: A pilot feasibility study.
AB - OBJECTIVE: Neurogenic bladder dysfunction, including neurogenic detrusor
overactivity (NDO) is one of the most clinically significant problems for persons
with spinal cord injury (SCI), affecting health and quality of life. Genital
nerve stimulation (GNS) can acutely inhibit NDO-related reflex bladder
contractions and increase bladder capacity. However, it is unknown if GNS can
improve urinary continence or help meet individuals' bladder management goals
during sustained use, which is required for GNS to be clinically effective.
DESIGN: Subjects maintained voiding diaries during a one-month control period
without stimulation, one month with at-home GNS, and one month after GNS.
Urodynamics and quality of life assessments were conducted after each treatment
period, and a satisfaction survey was taken at study completion. SETTING: Subject
screening and clinical procedures were conducted at the Louis Stokes Cleveland VA
Medical Center. Stimulation use and voiding diary entries were conducted in
subjects' homes. PARTICIPANTS: Subjects included five men with SCI and NDO.
INTERVENTIONS: This study tested one month of at-home portable non-invasive GNS.
OUTCOME MEASURES: The primary outcome measure was leakage events per day.
Secondary outcome measures included self-reported subject satisfaction, bladder
capacity, and stimulator use frequency. RESULTS: GNS reduced the number of
leakage events from 1.0 +/- 0.5 to 0.1 +/- 0.4 leaks per day in the four subjects
who reported incontinence data. All study participants were satisfied that GNS
met their bladder goals; wanted to continue using GNS; and would recommend it to
others. CONCLUSIONS: Short term at-home GNS reduced urinary incontinence and
helped subjects meet their bladder management goals. These data inform the design
of a long-term clinical trial testing of GNS as an approach to reduce NDO.
PMID- 29334339
TI - Impact of spasticity on transfers and activities of daily living in individuals
with spinal cord injury.
AB - CONTEXT/OBJECTIVE: For persons with spinal cord injury, spasticity commonly
interferes with activities of daily living such as transfers. Electromyography
can be used to objectively measure muscle spasms during transfers, but how
electromyographic measures relate to the impact spasticity has on life, or to
clinically-rated spasticity, is unclear. We aimed to characterize relationships
among spasm duration and magnitude, impact of spasticity on daily life, and a
clinical measure of extensor spasticity, as well as to determine reliability of
the electromyographic measures. DESIGN: Participants (N=19) underwent
electromyographic measurements of involuntary muscle activity (spasm duration and
magnitude) evoked in quadriceps muscles during transfers on two days. Impact of
spasticity on daily life was measured with the Spinal Cord Injury Spasticity
Evaluation Tool. Clinically-rated spasticity severity was measured with the
Spinal Cord Assessment Tool for Spastic reflexes. RESULTS: No significant
associations were found between impact of spasticity and spasm duration, spasm
magnitude, or clinical extensor spasticity score. Absolute and normalized spasm
duration were positively associated with clinical extensor spasticity score
(rho=0.510-0.667, P < 0.05). Spasm measures during transfers had good to
excellent day-to-day reliability (rho=0.656-0.846, P < 0.05). CONCLUSIONS:
Electromyographic and clinical measures of involuntary activity in the lower
extremity do not significantly relate to perceived impact of spasticity on daily
life. However, quadriceps spasm duration during transfers is related to
clinically-rated extensor spasticity. Electromyography is a reliable method of
quantifying quadriceps spasms during transfers. Future investigations should
identify factors that influence the impact of spasticity on life, which may help
direct treatment strategies to reduce problematic impact.
PMID- 29334340
TI - Identification of anti-filarial leads against aspartate semialdehyde
dehydrogenase of Wolbachia endosymbiont of Brugia malayi: combined molecular
docking and molecular dynamics approaches.
AB - Lymphatic filariasis is a debilitating vector borne parasitic disease that
infects human lymphatic system by nematode Brugia malayi. Currently available
anti-filarial drugs are effective only on the larval stages of parasite. So far,
no effective drugs are available for humans to treat filarial infections. In this
regard, aspartate semialdehyde dehydrogenase (ASDase) in lysine biosynthetic
pathway from Wolbachia endosymbiont Brugia malayi represents an attractive
therapeutic target for the development of novel anti-filarial agents. In this
present study, molecular modeling combined with molecular dynamics simulations
and structure-based virtual screening were performed to identify potent lead
molecules against ASDase. Based on Glide score, toxicity profile, binding
affinity and mode of interactions with the ASDase, five potent lead molecules
were selected. The molecular docking and dynamics results revealed that the amino
acid residues Arg103, Asn133, Cys134, Gln161, Ser164, Lys218, Arg239, His246, and
Asn321 plays a crucial role in effective binding of Top leads into the active
site of ASDase. The stability of the ASDase-lead complexes was confirmed by
running the 30 ns molecular dynamics simulations. The pharmacokinetic properties
of the identified lead molecules are in the acceptable range. Furthermore,
density functional theory and binding free energy calculations were performed to
rank the lead molecules. Thus, the identified lead molecules can be used for the
development of anti-filarial agents to combat the pathogenecity of Brugia malayi.
PMID- 29334341
TI - Thyroid-Related Research in Japan A Spotlight on Recent Important Contributions.
PMID- 29334343
TI - Breast-Milk Iodine Concentrations and Iodine Levels of Infants According to the
Iodine Status of the Country of Residence: A Systematic Review and Meta-Analysis.
AB - BACKGROUND: Iodine, an essential micronutrient, plays a critical role in normal
growth and development, especially during the first two years of life. This
systematic review and meta-analysis is among the first to evaluate breast-milk
iodine concentrations and infant iodine status in countries characterized by
iodine sufficiency or deficiency. METHODS: PubMed, Web of Science, Cochrane
Library, Google Scholar, and other relevant databases, as well as reference lists
of previous reviews, were searched for relevant studies published between 1986
and 2016. Mean or median breast-milk and infant urinary iodine concentrations,
along with other relevant data, were extracted from eligible studies. Each study
was assessed for quality and risk of bias. RESULTS: Of the 496 identified
studies, 57 met the criteria for inclusion in the meta-analysis. The mean
(confidence interval [CI]) iodine concentrations in maternal colostrum were 152.0
MUg/L [CI 106.2-198.7 MUg/L] and 57.8 MUg/L [CI 41.4-74.1 MUg/L] in iodine
sufficient and -deficient countries, respectively, indicating a significant
difference between the two iodine statuses. By contrast, the corresponding values
in mature milk did not differ significantly between mothers in iodine-sufficient
and -deficient countries (71.5 MUg/L [CI 51.0-92.0 MUg/L] and 28.0 MUg/L [CI
13.8 to 69.9 MUg/L], respectively]. The weighted urinary iodine levels [CIs] of
breast-fed infants in iodine-sufficient countries were significantly higher than
those in iodine-deficient countries (164.5 MUg/L [CI 116.4-212.7 MUg/L] vs. 70.4
MUg/L [CI 46.2-94.6 MUg/L]). Similarly, a significant difference was observed in
the pooled estimates of urinary iodine levels [CIs] among formula-fed infants in
iodine-sufficient versus iodine-deficient countries (310.3 MUg/L [CI 287.4-342.1
MUg/L] vs. 38.3 MUg/L [CI 23.4-53.2 MUg/L]). CONCLUSION: The meta-analysis
reveals that in iodine-sufficient countries, the mean iodine concentrations in
colostrum and mature breast milk corresponded to iodine sufficiency among
infants. The results are thus compatible with the international recommendation
that lactating women and infants younger than two years of age who reside in
iodine-sufficient countries do not require iodine supplementation.
PMID- 29334345
TI - Arm crank ergometry improves cardiovascular disease risk factors and community
mobility independent of body composition in high motor complete spinal cord
injury.
AB - OBJECTIVE: Evaluate the effect of aerobic exercise using arm crank ergometry
(ACE) in high motor complete (ISNCSCI A/B) spinal cord injury (SCI) as primarily
related to cardiovascular disease (CVD) risk factors and functional mobility and
secondarily to body composition and metabolic profiles. DESIGN: Longitudinal
interventional study at an academic medical center. METHODS: Ten previously
untrained participants (M8/F2, Age 36.7 y +/- 10.1, BMI 24.5 +/- 6.0) with high
motor complete SCI (C7-T5) underwent ACE exercise training 30 minutes/day * 3
days/week for 10 weeks at 70% VO2Peak. OUTCOME MEASURES: Primary outcome measures
were pre- and post-intervention changes in markers of cardiovascular fitness
(graded exercise testing (GXT): VO2, VO2Peak, respiratory quotient [RQ], GXT
time, peak power, and energy expenditure [EE]) and community mobility (time to
traverse a 100ft-5 degrees ramp, and 12-minute WC propulsion test). Secondary
outcome measures were changes in body composition and metabolic profiles (fasting
and area under the curve for glucose and insulin, homeostasis model assessment
[HOMA] for %beta-cell activity [%beta], %insulin sensitivity [%S], and insulin
resistance [IR], and Matsuda Index [ISIMatsuda]). RESULTS: Resting VO2, relative
VO2Peak, absolute VO2Peak, peak power, RQ, 12-minute WC propulsion, fasting
insulin, fasting G:I ratio, HOMA-%S, and HOMA-IR all significantly improved
following intervention (P < 0.05). There were no changes in body composition
(P>0.05). CONCLUSIONS: Ten weeks of ACE at 70% VO2Peak in high motor complete SCI
improves aerobic capacity, community mobility, and metabolic profiles independent
of changes in body composition.
PMID- 29334346
TI - In this issue: Prerequisites for precision medicine are genomics, computerised
medical record systems, and big data analytics.
PMID- 29334344
TI - Content validity and satisfaction with a caregiver-integrated web-based
rehabilitation intervention for persons with stroke.
AB - Background Family members provide valuable contributions during rehabilitation
after stroke, but frequently report higher incidences of burden, depression, and
social isolation during caregiving. Thus, effective interventions to reduce
stroke impact on the family are needed. Objectives To evaluate the content
validity and satisfaction of a caregiver-focused web-based intervention designed
to improve stroke survivor physical function while reducing caregiver negative
outcomes. Methods Caregivers of individuals with stroke (N = 6) and expert
rehabilitation researchers (N = 4) were presented with a novel, web-based
intervention (CARE-CITE) designed to foster problem-solving and skill-building
while facilitating caregiver involvement during constraint-induced movement
therapy. Caregivers rated CARE-CITE for usefulness, ease of use, acceptability,
and time to complete. Rehabilitation experts evaluated content for accuracy,
feasibility, acceptability, problem relevance and ease of use. Ratings were
assessed using a five-point Likert-type response scales (1 = strongly disagree to
5 = strongly agree). Results On average, all caregivers agreed or strongly agreed
that the modules were useful (4.42), easy to use (4.60), and acceptable (4.41).
Mean total satisfaction score was 4.45, and average review time was 15 min per
module. Expert reviewers agreed or strongly agreed that each module was accurate
(4.95), feasible (4.8), easy to use (4.86), acceptable (4.96), and had
appropriate problem relevance (4.65). Conclusions The CARE-CITE intervention may
be a viable program for caregivers of patients with stroke. Currently a pilot
study is underway to evaluate the impact of the intervention on caregiver mental
health, family conflict around stroke recovery and stroke survivor upper
extremity function.
PMID- 29334347
TI - Methods to Describe Referral Patterns in a Canadian Primary Care Electronic
Medical Record Database: Modelling Multilevel Count Data.
AB - BACKGROUND: A referral from a family physician (FP) to a specialist is an
inflection point in the patient journey, with potential implications for clinical
outcomes and health policy. Primary care electronic medical record (EMR)
databases offer opportunities to examine referral patterns. Until recently,
software techniques were not available to model these kinds of multi-level count
data. OBJECTIVE: To establish methodology for determining referral rates from
FPs to medical specialists using the Canadian Primary Care Sentinel Surveillance
Network (CPCSSN) EMR database. METHOD: Retrospective cohort study, mixed effects
and multi-level negative binomial regression modelling with 87,258 eligible
patients between 2007 and 2012. Mean referrals compared by patient sex, age,
chronic conditions, FP visits, and urban/rural practice location. Proportion of
variance in referral rates attributable to the patient and practice levels.
RESULTS: On average, males had 0.26, and females 0.31 referrals in a 12-month
period. Referrals were significantly higher for females, increased with age, FP
visits, and number of chronic conditions (p<.0001). Overall, 14% of the variance
in referrals could be attributed to the practice level, and 86% to patient level
characteristics. CONCLUSIONS: Both patient and practice characteristics
influenced referral patterns. The methodologic insights gained from this study
have relevance to future studies on many research questions that utilize count
data, both within primary care and broader health services research. The utility
of the CPCSSN database will continue to increase in tandem with data quality
improvements, providing a valuable resource to study Canadian referral patterns
over time.
PMID- 29334348
TI - Assessing the readiness of precision medicine interoperabilty: An exploratory
study of the National Institutes of Health genetic testing registry.
AB - BACKGROUND: Precision medicine involves three major innovations currently
taking place in healthcare: electronic health records, genomics, and big data.
A major challenge for healthcare providers, however, is understanding the
readiness for practical application of initiatives like precision medicine.
OBJECTIVE: To better understand the current state and challenges of precision
medicine interoperability using a national genetic testing registry as a starting
point, placed in the context of established interoperability formats. METHODS:
We performed an exploratory analysis of the National Institutes of Health Genetic
Testing Registry. Relevant standards included Health Level Seven International
Version 3 Implementation Guide for Family History, the Human Genome Organization
Gene Nomenclature Committee (HGNC) database, and Systematized Nomenclature of
Medicine - Clinical Terms (SNOMED CT). We analyzed the distribution of genetic
testing laboratories, genetic test characteristics, and standardized
genome/clinical code mappings, stratified by laboratory setting. RESULTS: There
were a total of 25472 genetic tests from 240 laboratories testing for
approximately 3632 distinct genes. Most tests focused on diagnosis, mutation
confirmation, and/or risk assessment of germline mutations that could be passed
to offspring. Genes were successfully mapped to all HGNC identifiers, but less
than half of tests mapped to SNOMED CT codes, highlighting significant gaps when
linking genetic tests to standardized clinical codes that explain the medical
motivations behind test ordering. Conclusion: While precision medicine could
potentially transform healthcare, successful practical and clinical application
will first require the comprehensive and responsible adoption of interoperable
standards, terminologies, and formats across all aspects of the precision
medicine pipeline.
PMID- 29334349
TI - Research Outputs of England's Hospital Episode Statistics (HES) Database:
Bibliometric Analysis.
AB - BACKGROUND: Hospital administrative data, such as those provided by the Hospital
Episode Statistics (HES) database in England, are increasingly being used for
research and quality improvement. To date, no study has tried to quantify and
examine trends in the use of HES for research purposes. OBJECTIVE: To examine
trends in the use of HES data for research. METHODS: Publications generated from
the use of HES data were extracted from PubMed and analysed. Publications from
1996 to 2014 were then examined further in the Science Citation Index (SCI) of
the Thompson Scientific Institute for Science Information (Web of Science) for
details of research specialty area. RESULTS: 520 studies, categorised into 44
specialty areas, were extracted from PubMed. The review showed an increase in
publications over the 18-year period with an average of 27 publications per year,
however with the majority of output observed in the latter part of the study
period. The highest number of publications was in the Health Statistics specialty
area. CONCLUSION: The use of HES data for research is becoming more common.
Increase in publications over time shows that researchers are beginning to take
advantage of the potential of HES data. Although HES is a valuable database,
concerns exist over the accuracy and completeness of the data entered. Clinicians
need to be more engaged with HES for the full potential of this database to be
harnessed.
PMID- 29334350
TI - Bespoke automation of medical workforce rostering using Google's free cloud
applications.
AB - BACKGROUND: Providing safe and consistent care requires optimal deployment of
medical staff. Ensuring this happens is a significant administrative burden due
to complex working patterns. OBJECTIVE: To describe a pilot feasibility study of
the automation of medical duty rostering in a busy tertiary Ophthalmology
department. METHODS: A cloud based web application was created using Google's
free cloud services. Users access the system via a website which hosts live
rosters, and use electronic forms to submit requests which are automatically
handled by Google App Scripts. RESULTS: Over a 2-year period (8/2014-6/2016), the
system processed 563 leave requests and 300 on call swaps automatically. 3,300
emails and 1,000 forms were automatically generated. User satisfaction was 100%
(n=24). DISCUSSION: Many time consuming aspects of roster management were
automated with significant time savings to all parties, allowing increased
clinical time for doctors involved in administration. Planning for safe staffing
levels was supported.
PMID- 29334351
TI - Integrating third-party telehealth records with the general practice electronic
medical record system: a solution.
AB - BACKGROUND: The implementation of telemonitoring at scale has been less
successful than anticipated, often hindered by clinicians' perceived increase in
workload. One important factor has been the lack of integration of patient
generated data (PGD) with the electronic medical record (EMR). Clinicians have
had problems accessing PGD on telehealth systems especially in patient
consultations in primary care. OBJECTIVE: To design a method to produce a report
of PGD that is available to clinicians through their routine EMR system. METHOD:
We modelled a system with a use case approach using Unified Modelling Language to
enable us to design a method of producing the required report. Anonymised PGD are
downloaded from a third-party telehealth system to National Health Service (NHS)
systems and linked to the patient record available in the hospital recording
system using the patient NHS ID through an interface accessed by healthcare
professionals. The telehealth data are then processed into a report using the
patient record. This report summarises the readings in graphical and tabular form
with an average calculated and with a recommended follow-up suggested if
required. The report is then disseminated to general practitioner practices
through routine document distribution pathways. RESULTS: This addition to the
telehealth system is viewed positively by clinicians. It has helped to greatly
increase the number of general practices using telemonitoring to manage blood
pressure in NHS Lothian.
PMID- 29334352
TI - The Multimorbidity Cluster Analysis Tool: Identifying Combinations and
Permutations of Multiple Chronic Diseases Using a Record-Level Computational
Analysis.
AB - INTRODUCTION: Multimorbidity, or the co-occurrence of multiple chronic health
conditions within an individual, is an increasingly dominant presence and burden
in modern health care systems. To fully capture its complexity, further research
is needed to uncover the patterns and consequences of these co-occurring health
states. As such, the Multimorbidity Cluster Analysis Tool and the accompanying
Multimorbidity Cluster Analysis Toolkit have been created to allow researchers to
identify distinct clusters that exist within a sample of participants or patients
living with multimorbidity. Development: The Tool and Toolkit were developed at
Western University in London, Ontario, Canada. This open-access computational
program (JAVA code and executable file) was developed and tested to support an
analysis of thousands of individual records and up to 100 disease diagnoses or
categories. APPLICATION: The computational program can be adapted to the
methodological elements of a research project, including type of data, type of
chronic disease reporting, measurement of multimorbidity, sample size and
research setting. The computational program will identify all existing, and
mutually exclusive, combinations and permutations within the dataset. An
application of this computational program is provided as an example, in which
more than 75,000 individual records and 20 chronic disease categories resulted in
the detection of 10,411 unique combinations and 24,647 unique permutations among
female and male patients. DISCUSSION: The Tool and Toolkit are now available for
use by researchers interested in exploring the complexities of multimorbidity.
Its careful use, and the comparison between results, will be valuable additions
to the nuanced understanding of multimorbidity.
PMID- 29334353
TI - Genesis of a UK Faculty of Clinical Informatics at a time of anticipation for
some, and ruby, golden and diamond celebrations for others.
AB - This Editorial marks the launch of the UK Faculty of Clinical Informatics (FCI)
at the time when non-clinically qualified informaticians are anticipating the
lauch of the Federation of Informatics Professionals in Health and Care (Fed
IP).
PMID- 29334354
TI - Real World Evidence to an eHealth tool: The 2017 top ten papers from Journal of
Innovation in Health Informatics.
AB - We report the top ten papers published by the Journal ofInnovation in Health
Informatics in 2017.
PMID- 29334355
TI - Retraction: Genetic characterization and assessment of demographic bottleneck in
Caspian horse population.
AB - [This delete the article DOI: 10.14715/cmb/2017.63.11.16.].
PMID- 29334358
TI - Fingerprints of a position-dependent Fermi velocity on scanning tunnelling
spectra of strained graphene.
AB - Nonuniform strain in graphene induces a position dependence of the Fermi
velocity, as recently demonstrated by scanning tunnelling spectroscopy
experiments. In this work, we study the effects of a position-dependent Fermi
velocity on the local density of states (LDOS) of strained graphene, with and
without the presence of a uniform magnetic field. The variation of LDOS obtained
from tight-binding calculations is successfully explained by analytical
expressions derived within the Dirac approach. These expressions also rectify a
rough Fermi velocity substitution used in the literature that neglects the strain
induced anisotropy. The reported analytical results could be useful for
understanding the nonuniform strain effects on scanning tunnelling spectra of
graphene, as well as when it is exposed to an external magnetic field.
PMID- 29334356
TI - p53 orchestrates DNA replication restart homeostasis by suppressing mutagenic
RAD52 and POLtheta pathways.
AB - Classically, p53 tumor suppressor acts in transcription, apoptosis, and cell
cycle arrest. Yet, replication-mediated genomic instability is integral to
oncogenesis, and p53 mutations promote tumor progression and drug-resistance. By
delineating human and murine separation-of-function p53 alleles, we find that p53
null and gain-of-function (GOF) mutations exhibit defects in restart of stalled
or damaged DNA replication forks that drive genomic instability, which
isgenetically separable from transcription activation. By assaying protein-DNA
fork interactions in single cells, we unveil a p53-MLL3-enabled recruitment of
MRE11 DNA replication restart nuclease. Importantly, p53 defects or depletion
unexpectedly allow mutagenic RAD52 and POLtheta pathways to hijack stalled forks,
which we find reflected in p53 defective breast-cancer patient COSMIC mutational
signatures. These data uncover p53 as a keystone regulator of replication
homeostasis within a DNA restart network. Mechanistically, this has important
implications for development of resistance in cancer therapy. Combined, these
results define an unexpected role for p53-mediated suppression of replication
genome instability.
PMID- 29334359
TI - Electronic and optical properties of spinel zinc ferrite: ab initio hybrid
functional calculations.
AB - Spinel ferrites in general show a rich interplay of structural, electronic, and
magnetic properties. Here, we particularly focus on zinc ferrite (ZFO), which has
been observed experimentally to crystallise in the cubic normal spinel structure.
However, its magnetic ground state is still under dispute. In addition, some
unusual magnetic properties in ZFO thin films or nanostructures have been
explained by a possible partial cation inversion and a different magnetic
interaction between the two cation sublattices of the spinel structure compared
to the crystalline bulk material. Here, density functional theory has been
applied to investigate the influence of different inversion degrees and magnetic
couplings among the cation sublattices on the structural, electronic, magnetic,
and optical properties. Effects of exchange and correlation have been modelled
using the generalised gradient approximation (GGA) together with the Hubbard '+U'
parameter, and the more elaborate hybrid functional PBE0. While the GGA+U
calculations yield an antiferromagnetically coupled normal spinel structure as
the ground state, in the PBE0 calculations the ferromagnetically coupled normal
spinel is energetically slightly favoured, and the hybrid functional calculations
perform much better with respect to structural, electronic and optical
properties.
PMID- 29334357
TI - Differential requirements of androgen receptor in luminal progenitors during
prostate regeneration and tumor initiation.
AB - Master regulatory genes of tissue specification play key roles in stem/progenitor
cells and are often important in cancer. In the prostate, androgen receptor (AR)
is a master regulator essential for development and tumorigenesis, but its
specific functions in prostate stem/progenitor cells have not been elucidated. We
have investigated AR function in CARNs (CAstration-Resistant Nkx3.1-expressing
cells), a luminal stem/progenitor cell that functions in prostate regeneration.
Using genetically--engineered mouse models and novel prostate epithelial cell
lines, we find that progenitor properties of CARNs are largely unaffected by AR
deletion, apart from decreased proliferation in vivo. Furthermore, AR loss
suppresses tumor formation after deletion of the Pten tumor suppressor in CARNs;
however, combined Pten deletion and activation of oncogenic Kras in AR-deleted
CARNs result in tumors with focal neuroendocrine differentiation. Our findings
show that AR modulates specific progenitor properties of CARNs, including their
ability to serve as a cell of origin for prostate cancer.
PMID- 29334360
TI - Self-consistent description of local density dynamics in simple liquids. The case
of molten lithium.
AB - The dynamic structure factor is the quantity, which can be measured by means of
Brillouin light-scattering as well as by means of inelastic scattering of
neutrons and x-rays. The spectral (or frequency) moments of the dynamic structure
factor define directly the sum rules of the scattering law. The theoretical
scheme formulated in this study allows one to describe the dynamics of local
density fluctuations in simple liquids and to obtain the expression of the
dynamic structure factor in terms of the spectral moments. The theory satisfies
all the sum rules, and the obtained expression for the dynamic structure factor
yields correct extrapolations into the hydrodynamic limit as well as into the
free-particle dynamics limit. We discuss correspondence of this theory with the
generalized hydrodynamics and with the viscoelastic models, which are commonly
used to analyze the data of inelastic neutron and x-ray scattering in liquids. In
particular, we reveal that the postulated condition of the viscoelastic model for
the memory function can be directly obtained within the presented theory. The
dynamic structure factor of liquid lithium is computed on the basis of the
presented theory, and various features of the scattering spectra are evaluated.
It is found that the theoretical results are in agreement with inelastic x-ray
scattering data.
PMID- 29334361
TI - Engineering the spin polarization of one-dimensional electrons.
AB - We present results of magneto-focusing on the controlled monitoring of spin
polarization within a one-dimensional (1D) channel, and its subsequent effect on
modulating the spin-orbit interaction (SOI) in a 2D GaAs electron gas. We
demonstrate that electrons within a 1D channel can be partially spin polarized as
the effective length of the 1D channel is varied in agreement with the
theoretical prediction. Such polarized 1D electrons when injected into a 2D
region result in a split in the odd-focusing peaks, whereas the even peaks remain
unaffected (single peak). On the other hand, the unpolarized electrons do not
affect the focusing spectrum and the odd and even peaks remain as single peaks,
respectively. The split in odd-focusing peaks is evidence of direct measurement
of spin polarization within a 1D channel, where each sub-peak represents the
population of a particular spin state. Confirmation of the spin splitting is
determined by a selective modulation of the focusing peaks due to the Zeeman
energy in the presence of an in-plane magnetic field. We suggest that the SOI in
the 2D regime is enhanced by a stream of polarized 1D electrons. The spatial
control of spin states of injected 1D electrons and the possibility of tuning the
SOI may open up a new regime of spin-engineering with application in future
quantum information schemes.
PMID- 29334362
TI - Investigation of resistance switching in SiO x RRAM cells using a 3D multi-scale
kinetic Monte Carlo simulator.
AB - We employ an advanced three-dimensional (3D) electro-thermal simulator to explore
the physics and potential of oxide-based resistive random-access memory (RRAM)
cells. The physical simulation model has been developed recently, and couples a
kinetic Monte Carlo study of electron and ionic transport to the self-heating
phenomenon while accounting carefully for the physics of vacancy generation and
recombination, and trapping mechanisms. The simulation framework successfully
captures resistance switching, including the electroforming, set and reset
processes, by modeling the dynamics of conductive filaments in the 3D space. This
work focuses on the promising yet less studied RRAM structures based on silicon
rich silica (SiO x ) RRAMs. We explain the intrinsic nature of resistance
switching of the SiO x layer, analyze the effect of self-heating on device
performance, highlight the role of the initial vacancy distributions acting as
precursors for switching, and also stress the importance of using 3D physics
based models to capture accurately the switching processes. The simulation work
is backed by experimental studies. The simulator is useful for improving our
understanding of the little-known physics of SiO x resistive memory devices, as
well as other oxide-based RRAM systems (e.g. transition metal oxide RRAMs),
offering design and optimization capabilities with regard to the reliability and
variability of memory cells.
PMID- 29334363
TI - Macrophage membrane-coated iron oxide nanoparticles for enhanced photothermal
tumor therapy.
AB - Nanotechnology possesses the potential to revolutionize the diagnosis and
treatment of tumors. The ideal nanoparticles used for in vivo cancer therapy
should have long blood circulation times and active cancer targeting.
Additionally, they should be harmless and invisible to the immune system. Here,
we developed a biomimetic nanoplatform with the above properties for cancer
therapy. Macrophage membranes were reconstructed into vesicles and then coated
onto magnetic iron oxide nanoparticles (Fe3O4 NPs). Inherited from the Fe3O4 core
and the macrophage membrane shell, the resulting Fe3O4@MM NPs exhibited good
biocompatibility, immune evasion, cancer targeting and light-to-heat conversion
capabilities. Due to the favorable in vitro and in vivo properties, biomimetic
Fe3O4@MM NPs were further used for highly effective photothermal therapy of
breast cancer in nude mice. Surface modification of synthetic nanomaterials with
biomimetic cell membranes exemplifies a novel strategy for designing an ideal
nanoplatform for translational medicine.
PMID- 29334364
TI - Compactness of viral genomes: effect of disperse and localized random mutations.
AB - Genomes of single-stranded RNA viruses have evolved to optimize several
concurrent properties. One of them is the architecture of their genomic folds,
which must not only feature precise structural elements at specific positions,
but also allow for overall spatial compactness. The latter was shown to be
disrupted by random synonymous mutations, a disruption which can consequently
negatively affect genome encapsidation. In this study, we use three mutation
schemes with different degrees of locality to mutate the genomes of phage MS2 and
Brome Mosaic virus in order to understand the observed sensitivity of the global
compactness of their folds. We find that mutating local stretches of their
genomes' sequence or structure is less disruptive to their compactness compared
to inducing randomly-distributed mutations. Our findings are indicative of a
mechanism for the conservation of compactness acting on a global scale of the
genomes, and have several implications for understanding the interplay between
local and global architecture of viral RNA genomes.
PMID- 29334365
TI - 12th FluoroFest International Workshop April 24-26, 2017.
PMID- 29334366
TI - Modified Colistin Regimen for Critically Ill Patients with Acute Renal Impairment
and Continuous Renal Replacement Therapy.
AB - Colistin is a last resort antibiotic to treat multidrug-resistant Gram-negative
bacteria infections. Colistin is administered intravenously in the form of its
inactive prodrug colistin methanesulfonate (CMS). For patients with acute kidney
impairment and continuous renal replacement therapy high extracorporeal clearance
may cause a substantial removal of active colistin from the bloodstream,
eventually decreasing its antibacterial efficacy. Currently recommended doses of
CMS may therefore be inadequate for these patients. We report on the potential
value of a modified regimen that adopts a loading dose of CMS (bolus of 9 MU vs.
conventional 3 MU every 8 h), followed by maintenance (3 MU every 8 h).
Preliminary pharmacokinetic evidence for the feasibility and efficacy of this
regimen is described for 2 patients.
PMID- 29334367
TI - Unmanipulated haploidentical transplantation conditioning with busulfan,
cyclophosphamide and anti-thymoglobulin for adult severe aplastic anaemia.
AB - We conducted a retrospective analysis to evaluate outcomes of haploidentical
transplantation in adult severe aplastic anaemia (SAA) patients. Fifty-one adults
received haploidentical transplantation between May 2011 and December 2016.
Patients were administered busulfan (Bu), cyclophosphamide (Cy) and anti
thymoglobulin (ATG) as conditioning regimens, followed by bone marrow and
peripheral blood transplantation. The patients' median age was 25 years. Forty
nine patients survived for more than 28 days and all achieved donor myeloid
engraftment. The median time for myeloid engraftment and platelet recovery was 13
days (range, 10-21) and 17.5 (range, 7-101) days. The cumulative incidence (CI)
of grade II-IV and III-IV acute GvHD) was 20.00+/-0.33% and 6.00+/-0.12%,
respectively. The incidence of chronic GvHD was 14.00+/-0.36% and 25.90+/-0.71%,
and that of moderate-severe chronic GvHD was 2.51+/-0.06% and 6.92+/-0.25% at 1
and 3 years, respectively. The 3-year estimated overall survival and failure-free
survival were both 83.5+/-5.4% with a median follow-up of 21.1 months.
Multivariate analysis showed hematopoietic cell transplantation-specific
comorbidity index (HCT-CI) score of ?3 was significantly associated with worse
outcome. Haploidentical transplantation conditioning including Bu/Cy/ATG was a
safe and effective strategy for adult SAA patients, and HCT-CI might be an
outcome predictor in these patients.
PMID- 29334368
TI - Visualizing detailed postdoctoral employment trends using a new career outcome
taxonomy.
PMID- 29334369
TI - Dual gene activation and knockout screen reveals directional dependencies in
genetic networks.
AB - Understanding the direction of information flow is essential for characterizing
how genetic networks affect phenotypes. However, methods to find genetic
interactions largely fail to reveal directional dependencies. We combine two
orthogonal Cas9 proteins from Streptococcus pyogenes and Staphylococcus aureus to
carry out a dual screen in which one gene is activated while a second gene is
deleted in the same cell. We analyze the quantitative effects of activation and
knockout to calculate genetic interaction and directionality scores for each gene
pair. Based on the results from over 100,000 perturbed gene pairs, we reconstruct
a directional dependency network for human K562 leukemia cells and demonstrate
how our approach allows the determination of directionality in activating genetic
interactions. Our interaction network connects previously uncharacterized genes
to well-studied pathways and identifies targets relevant for therapeutic
intervention.
PMID- 29334370
TI - Scaffolds that mimic antigen-presenting cells enable ex vivo expansion of primary
T cells.
AB - Therapeutic ex vivo T-cell expansion is limited by low rates and T-cell products
of limited functionality. Here we describe a system that mimics natural antigen
presenting cells (APCs) and consists of a fluid lipid bilayer supported by
mesoporous silica micro-rods. The lipid bilayer presents membrane-bound cues for
T-cell receptor stimulation and costimulation, while the micro-rods enable
sustained release of soluble paracrine cues. Using anti-CD3, anti-CD28, and
interleukin-2, we show that the APC-mimetic scaffolds (APC-ms) promote two- to
tenfold greater polyclonal expansion of primary mouse and human T cells compared
with commercial expansion beads (Dynabeads). The efficiency of expansion depends
on the density of stimulatory cues and the amount of material in the starting
culture. Following a single stimulation, APC-ms enables antigen-specific
expansion of rare cytotoxic T-cell subpopulations at a greater magnitude than
autologous monocyte-derived dendritic cells after 2 weeks. APC-ms support over
fivefold greater expansion of restimulated CD19 CAR-T cells than Dynabeads, with
similar efficacy in a xenograft lymphoma model.
PMID- 29334371
TI - Cooperative targeting of melanoma heterogeneity with an AXL antibody-drug
conjugate and BRAF/MEK inhibitors.
AB - Intratumor heterogeneity is a key factor contributing to therapeutic failure and,
hence, cancer lethality. Heterogeneous tumors show partial therapy responses,
allowing for the emergence of drug-resistant clones that often express high
levels of the receptor tyrosine kinase AXL. In melanoma, AXL-high cells are
resistant to MAPK pathway inhibitors, whereas AXL-low cells are sensitive to
these inhibitors, rationalizing a differential therapeutic approach. We developed
an antibody-drug conjugate, AXL-107-MMAE, comprising a human AXL antibody linked
to the microtubule-disrupting agent monomethyl auristatin E. We found that AXL
107-MMAE, as a single agent, displayed potent in vivo anti-tumor activity in
patient-derived xenografts, including melanoma, lung, pancreas and cervical
cancer. By eliminating distinct populations in heterogeneous melanoma cell pools,
AXL-107-MMAE and MAPK pathway inhibitors cooperatively inhibited tumor growth.
Furthermore, by inducing AXL transcription, BRAF/MEK inhibitors potentiated the
efficacy of AXL-107-MMAE. These findings provide proof of concept for the premise
that rationalized combinatorial targeting of distinct populations in
heterogeneous tumors may improve therapeutic effect, and merit clinical
validation of AXL-107-MMAE in both treatment-naive and drug-resistant cancers in
mono- or combination therapy.
PMID- 29334372
TI - Pharmacological blockade of ASCT2-dependent glutamine transport leads to
antitumor efficacy in preclinical models.
AB - The unique metabolic demands of cancer cells underscore potentially fruitful
opportunities for drug discovery in the era of precision medicine. However,
therapeutic targeting of cancer metabolism has led to surprisingly few new drugs
to date. The neutral amino acid glutamine serves as a key intermediate in
numerous metabolic processes leveraged by cancer cells, including biosynthesis,
cell signaling, and oxidative protection. Herein we report the preclinical
development of V-9302, a competitive small molecule antagonist of transmembrane
glutamine flux that selectively and potently targets the amino acid transporter
ASCT2. Pharmacological blockade of ASCT2 with V-9302 resulted in attenuated
cancer cell growth and proliferation, increased cell death, and increased
oxidative stress, which collectively contributed to antitumor responses in vitro
and in vivo. This is the first study, to our knowledge, to demonstrate the
utility of a pharmacological inhibitor of glutamine transport in oncology,
representing a new class of targeted therapy and laying a framework for paradigm
shifting therapies targeting cancer cell metabolism.
PMID- 29334374
TI - Transitory presence of myeloid-derived suppressor cells in neonates is critical
for control of inflammation.
AB - Myeloid-derived suppressor cells (MDSCs) are pathologically activated and
relatively immature myeloid cells that have been implicated in the immunological
regulation of many pathologic conditions. Phenotypically and morphologically,
MDSCs are similar to neutrophils (PMN-MDSCs) and monocytes (M-MDSCs). However,
they have potent suppressive activity and distinct gene expression profiles and
biochemical characteristics. No or very few MDSCs are observed in steady-state
physiological conditions. Therefore, until recently, accumulation of MDSCs was
considered a consequence of pathological processes or pregnancy. Here, we report
that MDSCs with a potent ability to suppress T cells are present during the first
weeks of life in mice and humans. MDSC suppressive activity was triggered by
lactoferrin and mediated by nitric oxide, PGE2, and S100A9 and S100A8 proteins.
MDSCs from newborns had a transcriptome similar to that of tumor MDSCs, but with
strong upregulation of an antimicrobial gene network, and had potent
antibacterial activity. MDSCs played a critical role in control of experimental
necrotizing enterocolitis (NEC) in newborn mice. MDSCs in infants with very low
weight, who are prone to NEC, had lower MDSC levels and suppressive activity than
did infants with normal weight. Thus, the transitory presence of MDSCs may be
critical for regulation of inflammation in newborns.
PMID- 29334373
TI - Prevention of tuberculosis in rhesus macaques by a cytomegalovirus-based vaccine.
AB - Despite widespread use of the bacille Calmette-Guerin (BCG) vaccine, tuberculosis
(TB) remains a leading cause of global mortality from a single infectious agent
(Mycobacterium tuberculosis or Mtb). Here, over two independent Mtb challenge
studies, we demonstrate that subcutaneous vaccination of rhesus macaques (RMs)
with rhesus cytomegalovirus vectors encoding Mtb antigen inserts (hereafter
referred to as RhCMV/TB)-which elicit and maintain highly effector
differentiated, circulating and tissue-resident Mtb-specific CD4+ and CD8+ memory
T cell responses-can reduce the overall (pulmonary and extrapulmonary) extent of
Mtb infection and disease by 68%, as compared to that in unvaccinated controls,
after intrabronchial challenge with the Erdman strain of Mtb at ~1 year after the
first vaccination. Fourteen of 34 RhCMV/TB-vaccinated RMs (41%) across both
studies showed no TB disease by computed tomography scans or at necropsy after
challenge (as compared to 0 of 17 unvaccinated controls), and ten of these RMs
were Mtb-culture-negative for all tissues, an exceptional long-term vaccine
effect in the RM challenge model with the Erdman strain of Mtb. These results
suggest that complete vaccine-mediated immune control of highly pathogenic Mtb is
possible if immune effector responses can intercept Mtb infection at its earliest
stages.
PMID- 29334375
TI - A small-molecule inhibitor of the ubiquitin activating enzyme for cancer
treatment.
AB - The ubiquitin-proteasome system (UPS) comprises a network of enzymes that is
responsible for maintaining cellular protein homeostasis. The therapeutic
potential of this pathway has been validated by the clinical successes of a
number of UPS modulators, including proteasome inhibitors and immunomodulatory
imide drugs (IMiDs). Here we identified TAK-243 (formerly known as MLN7243) as a
potent, mechanism-based small-molecule inhibitor of the ubiquitin activating
enzyme (UAE), the primary mammalian E1 enzyme that regulates the ubiquitin
conjugation cascade. TAK-243 treatment caused depletion of cellular ubiquitin
conjugates, resulting in disruption of signaling events, induction of proteotoxic
stress, and impairment of cell cycle progression and DNA damage repair pathways.
TAK-243 treatment caused death of cancer cells and, in primary human xenograft
studies, demonstrated antitumor activity at tolerated doses. Due to its
specificity and potency, TAK-243 allows for interrogation of ubiquitin biology
and for assessment of UAE inhibition as a new approach for cancer treatment.
PMID- 29334377
TI - Detecting hierarchical genome folding with network modularity.
AB - Mammalian genomes are folded in a hierarchy of compartments, topologically
associating domains (TADs), subTADs and looping interactions. Here, we describe
3DNetMod, a graph theory-based method for sensitive and accurate detection of
chromatin domains across length scales in Hi-C data. We identify nested,
partially overlapping TADs and subTADs genome wide by optimizing network
modularity and varying a single resolution parameter. 3DNetMod can be applied
broadly to understand genome reconfiguration in development and disease.
PMID- 29334378
TI - Supermultiplexed optical imaging and barcoding with engineered polyynes.
AB - Optical multiplexing has a large impact in photonics, the life sciences and
biomedicine. However, current technology is limited by a 'multiplexing ceiling'
from existing optical materials. Here we engineered a class of polyyne-based
materials for optical supermultiplexing. We achieved 20 distinct Raman
frequencies, as 'Carbon rainbow', through rational engineering of conjugation
length, bond-selective isotope doping and end-capping substitution of polyynes.
With further probe functionalization, we demonstrated ten-color organelle imaging
in individual living cells with high specificity, sensitivity and photostability.
Moreover, we realized optical data storage and identification by combinatorial
barcoding, yielding to our knowledge the largest number of distinct spectral
barcodes to date. Therefore, these polyynes hold great promise in live-cell
imaging and sorting as well as in high-throughput diagnostics and screening.
PMID- 29334376
TI - Positively selected enhancer elements endow osteosarcoma cells with metastatic
competence.
AB - Metastasis results from a complex set of traits acquired by tumor cells, distinct
from those necessary for tumorigenesis. Here, we investigate the contribution of
enhancer elements to the metastatic phenotype of osteosarcoma. Through epigenomic
profiling, we identify substantial differences in enhancer activity between
primary and metastatic human tumors and between near isogenic pairs of highly
lung metastatic and nonmetastatic osteosarcoma cell lines. We term these regions
metastatic variant enhancer loci (Met-VELs). Met-VELs drive coordinated waves of
gene expression during metastatic colonization of the lung. Met-VELs cluster
nonrandomly in the genome, indicating that activity of these enhancers and
expression of their associated gene targets are positively selected. As evidence
of this causal association, osteosarcoma lung metastasis is inhibited by global
interruptions of Met-VEL-associated gene expression via pharmacologic BET
inhibition, by knockdown of AP-1 transcription factors that occupy Met-VELs, and
by knockdown or functional inhibition of individual genes activated by Met-VELs,
such as that encoding coagulation factor III/tissue factor (F3). We further show
that genetic deletion of a single Met-VEL at the F3 locus blocks metastatic cell
outgrowth in the lung. These findings indicate that Met-VELs and the genes they
regulate play a functional role in metastasis and may be suitable targets for
antimetastatic therapies.
PMID- 29334379
TI - Highly parallel direct RNA sequencing on an array of nanopores.
AB - Sequencing the RNA in a biological sample can unlock a wealth of information,
including the identity of bacteria and viruses, the nuances of alternative
splicing or the transcriptional state of organisms. However, current methods have
limitations due to short read lengths and reverse transcription or amplification
biases. Here we demonstrate nanopore direct RNA-seq, a highly parallel, real
time, single-molecule method that circumvents reverse transcription or
amplification steps. This method yields full-length, strand-specific RNA
sequences and enables the direct detection of nucleotide analogs in RNA.
PMID- 29334380
TI - Light-activated chemical probing of nucleobase solvent accessibility inside
cells.
AB - The discovery of functional RNAs that are critical for normal and disease
physiology continues to expand at a breakneck pace. Many RNA functions are
controlled by the formation of specific structures, and an understanding of each
structural component is necessary to elucidate its function. Measuring solvent
accessibility intracellularly with experimental ease is an unmet need in the
field. Here, we present a novel method for probing nucleobase solvent
accessibility, Light Activated Structural Examination of RNA (LASER). LASER
depends on light activation of a small molecule, nicotinoyl azide (NAz), to
measure solvent accessibility of purine nucleobases. In vitro, this technique
accurately monitors solvent accessibility and identifies rapid structural changes
resulting from ligand binding in a metabolite-responsive RNA. LASER probing can
further identify cellular RNA-protein interactions and unique intracellular RNA
structures. Our photoactivation technique provides an adaptable framework to
structurally characterize solvent accessibility of RNA in many environments.
PMID- 29334382
TI - A de novo enzyme catalyzes a life-sustaining reaction in Escherichia coli.
AB - Producing novel enzymes that are catalytically active in vitro and biologically
functional in vivo is a key goal of synthetic biology. Here we describe Syn-F4,
the first de novo protein that meets both criteria. Purified Syn-F4 hydrolyzes
the siderophore ferric enterobactin, and expression of Syn-F4 allows an inviable
strain of Escherichia coli to grow in iron-limited medium. These findings
demonstrate that entirely new sequences can provide life-sustaining enzymatic
functions in living organisms.
PMID- 29334383
TI - A simple method for determining the ligand affinity toward a zinc-enzyme model by
using a TAMRA/TAMRA interaction.
AB - Thiolate coordination to zinc(ii) ions occurs widely in such functional
biomolecules as zinc enzymes or zinc finger proteins. Here, we introduce a simple
method for determining the affinity of ligands toward the zinc-enzyme active
center model tetramethylrhodamine (TAMRA)-labeled 1,4,7,10-tetraazacyclododecane
(cyclen)-zinc(ii) complex (TAMRA-ZnL). The 1 : 1 complexation of TAMRA-labeled
cysteine (TAMRA-Cys) with TAMRA-ZnL (each at 2.5 MUM), in which the TAMRA
moieties approach one another closely, induces remarkable changes in the visible
absorption and fluorescence spectra at pH 7.4 and 25 degrees C. The 1 : 1
complex formation constant (K = [thiolate-bound zinc(ii) complex]/[uncomplexed
TAMRA-ZnL][uncomplexed TAMRA-Cys], M-1) was determined to be 106.7 M-1 from a
Job's plot of the absorbances at 552 nm. By a ligand-competition method with the
1 : 1 complexation equilibrium, analogous K values for thiol-containing ligands,
such as N-acetyl-l-cysteine, l-glutathione, and N-acetyl-l-cysteinamide, were
evaluated to have similar values of about 104 M-1. As a result of the ligand
affinities to TAMRA-ZnL, nonlabeled zinc(ii)-cyclen induced remarkable
stabilization of the reduced form of l-glutathione and a cysteine-containing
enolase peptide to aerial oxidation in aqueous solution at pH 7.4 and 25 degrees
C.
PMID- 29334381
TI - The molecular basis of subtype selectivity of human kinin G-protein-coupled
receptors.
AB - G-protein-coupled receptors (GPCRs) are the most important signal transducers in
higher eukaryotes. Despite considerable progress, the molecular basis of subtype
specific ligand selectivity, especially for peptide receptors, remains unknown.
Here, by integrating DNP-enhanced solid-state NMR spectroscopy with advanced
molecular modeling and docking, the mechanism of the subtype selectivity of human
bradykinin receptors for their peptide agonists has been resolved. The conserved
middle segments of the bound peptides show distinct conformations that result in
different presentations of their N and C termini toward their receptors. Analysis
of the peptide-receptor interfaces reveals that the charged N-terminal residues
of the peptides are mainly selected through electrostatic interactions, whereas
the C-terminal segments are recognized via both conformations and interactions.
The detailed molecular picture obtained by this approach opens a new gateway for
exploring the complex conformational and chemical space of peptides and peptide
analogs for designing GPCR subtype-selective biochemical tools and drugs.
PMID- 29334384
TI - Micrometer-sized dihydrogenphosphate-intercalated layered double hydroxides:
synthesis, selective infrared absorption properties, and applications as
agricultural films.
AB - High-performance heat-retention agents for multifunctional green agricultural
films are today largely suitable to increase the production yield as well as to
save energy. Here, an adapted ammonia releasing hydrothermal method was used to
produce a series of micrometer-sized carbonate-layered double hydroxide (CO3-LDH)
precursors of sizes ranging from 1.32 MUm to 8.64 MUm by simply adjusting the
feeding Mg2+ concentration from 0.80 mol L-1 to 0.20 mol L-1. From these pristine
LDH materials, MUm-sized dihydrogenphosphate-intercalated LDHs (H2PO4-LDHs) were
prepared by an anion-exchange method. The structure, the platelet size, and the
associated selective IR absorption properties of the H2PO4-LDH and the derivative
H2PO4-LDH/EVA composite as well as the related visible transmittance and the
photostability of the H2PO4-LDH/EVA film were investigated. The results show that
the selective IR absorption in the wavelength range of 7-14 MUm enabling the heat
retention of the H2PO4-LDHs and H2PO4-LDH/EVA composites depends on the
corresponding number-averaged particle size of H2PO4-LDH in the range of 2.01 MUm
to 8.80 MUm. Compared with EVA, the H2PO4-LDH/EVA composites demonstrate a
significant improvement of selective IR absorption, while maintaining acceptable
visible transmittance, and similar photostability. An optimized particle size of
H2PO4-LDH of ca. 5.85 MUm leads to 60% selective IR absorption and 64% selective
IR absorption when dispersed in EVA, while the polymer free of filler exhibits
less than 50% absorption in the 7-14 MUm IR domain.
PMID- 29334385
TI - Mechanical stability of a nanotube from monolayer black phosphorus with the [110]
direction as the tube's circumference or generatrix.
AB - The mechanical properties of black phosphorus (BP) are anisotropic.
Correspondingly, the properties of the nanotubes formed by bending the same BP
ribbon along different directions are different as well. When bending the ribbon
along the [110] direction (i.e., stair direction), or along its perpendicular
direction (i.e., ps-direction), s- or ps-BPNT can be obtained. The two types of
BPNTs are investigated via molecular dynamics (MD) simulations on their thermal
and mechanical properties. The results indicate that, for the thermal stability
of the s-BPNTs with similar diameters, s-BPNT is weaker than a-BPNTs (armchair
type) but stronger than ps-BPNT, and z-BPNT (zigzag type) is the weakest one. In
general, a-BPNT has larger compressive or tensile strength, while s-BPNT and ps
BPNT can bear larger deformation. Under uniaxial compression, s-BPNT has two
different breaking patterns at different temperatures. The peculiar properties
illustrate the wider application of BPNTs in nanodevices under large deformation.
PMID- 29334386
TI - Organic-inorganic hybrids having a talc-like structure as suitable hosts to guest
a wide range of species.
AB - The sol-gel process involving hydrolysis and condensation reactions is an
attractive way to form siloxane based hybrid materials since it is a one-step
method performed under mild conditions. Organic-inorganic hybrids having a talc
like structure (TLH) can be obtained using this procedure starting from
organotrialkoxysilanes having the formula R-Si(OR')3 (where R stands for an
organic moiety and R' for a methyl or ethyl group) with different
functionalities, an aqueous or ethanolic solution of a magnesium salt, and in
some cases, an aqueous solution of sodium hydroxide. In this way, the organic
chains are covalently bonded to the silicon of the tetrahedral sheets, pointing
toward the interlayer space. The interesting feature in this case is that as many
organotrialkoxysilanes are on the market, a wide range of organic moieties can be
introduced in the interlayer space leading to applications in various fields.
This review highlights the latest trends and the multifaceted applications of
these functional layered compounds.
PMID- 29334387
TI - A utility for organoleads: selective alkyl and aryl group transfer to tin.
AB - Me4Pb and Ph4Pb readily transfer methyl or phenyl groups to an equivalent molar
ratio of tin(iv) chlorides in the order SnCl4 > MeSnCl3 > Me2SnCl2 > Me3SnCl,
often in a selective manner. Me3PbCl and Ph3PbCl specifically transfer a single
methyl/phenyl group under the same reaction conditions to produce recovered
yields in >75%. Specific transfer of 2 methyl groups from PbMe4 can be achieved
at elevated temperatures and/or a 2 : 1 molar ratio Pb : Sn.
PMID- 29334388
TI - Catalytic (de)hydrogenation promoted by non-precious metals - Co, Fe and Mn:
recent advances in an emerging field.
AB - Catalytic hydrogenation and dehydrogenation reactions form the core of the modern
chemical industry. This vast class of reactions is found in any part of chemical
synthesis starting from the milligram-scale exploratory organic chemistry to the
multi-ton base chemicals production. Noble metal catalysis has long been the key
driving force in enabling these transformations with carbonyl substrates and
their nitrogen-containing counterparts. This review is aimed at introducing the
reader to the remarkable progress made in the last three years in the development
of base metal catalysts for hydrogenations and dehydrogenative transformations.
PMID- 29334389
TI - Effect of coordination geometry on the magnetic properties of a series of Ln2 and
Ln4 hydroxo clusters.
AB - A series of three isostructural tetranuclear complexes with the general molecular
formula [Ln4(MU3-OH)4(L)4(MU2-piv)4(MeOH)4] (Ln = Gd 1, Dy 2 and Ho 3; LH = [1,3
bis(o-methoxyphenyl)-propane-1,3-dione]) were isolated and unambiguously
characterized by single crystal XRD. Under similar reaction conditions, simply
changing the co-ligand from pivalate to 2,6-bis(hydroxymethyl)-p-cresol (LH'3)
led to the isolation of dinuclear Ln(iii) complexes with the general molecular
formula [Ln2(L)4(MU2-LH'2)2].4DMF (Ln = Gd 4, Dy 5 and Ho 6). Direct current
magnetic susceptibility data studies on the polycrystalline sample of 1-6 and the
results reveal the existence of weak antiferromagnetic exchange interactions
between the lanthanide ions in 1 which is evident from the spin Hamiltonian (SH)
parameters (J1 = -0.055 cm-1 and g = 2.01) extracted by fitting chiMT(T). On the
other hand, though complex 4 exhibits weak antiferromagnetic coupling (J1 =
0.048 cm-1 and g = 1.99) between the Gd(iii) ions, the chiMT(T) data of complexes
5 and 6 unambiguously disclose the presence of ferromagnetic interactions between
Dy(iii) and Tb(iii) ions at lower temperature. Magnetization relaxation dynamics
studies performed on 2 show frequency dependent out-of-phase susceptibility
signals in the presence of an optimum external magnetic field of 0.5 kOe. In
contrast, complex 5 shows slow magnetization relaxation with an effective energy
barrier (Ueff) of 38.17 cm-1 with a pre-exponential factor (tau0) of 1.85 * 10-6
s. The magnetocaloric effect (MCE) of complexes 1 and 4 was extracted from the
detailed magnetization measurement and the change in the magnetic entropy (
DeltaSm) of 1 and 4 was found to be 25.57 J kg-1 K-1 and 12.93 J kg-1 K-1,
respectively, at 3.0 K for DeltaH = 70 kOe.
PMID- 29334390
TI - Smartphone integrated optoelectrowetting (SiOEW) for on-chip sample processing
and microscopic detection of water quality.
AB - With the increasing capabilities and ubiquity of smartphones and their associated
digital cameras, this study presents a smartphone integrated optoelectrowetting
(SiOEW) device as a simple, portable tool capable of on-chip water sample
preparation and microscopic detection of the target cells in water samples, which
significantly reduce the detection time and the labor cost required for water
quality monitoring. A commercially available smartphone is used as a low
intensity portable light source to perform optoelectrowetting (OEW)-based
microfluidic operations such as droplet transportation, merging, mixing, and
immobilization on a hydrophobic detection zone. Furthermore, a built-in
smartphone camera allows on-chip microscopic detection of water quality with a
45* magnification. We have experimentally demonstrated that the SiOEW platform is
able not only to automate the sample processing of marine water including the
target algae cells (Amphiprora sp.) and staining reagents fluorescein diacetate
(FDA) and 5-chloromethylfluorescein diacetate (CMFDA), but also detect the
fluorescence signals emitted from the target cells in water samples and count
their populations. Using the smartphone, the collected information (e.g. the
location of the water sample collected and the time it was detected, the number
of the target cells, etc.) can be rapidly and wirelessly shared with a central
host such as an environmental regulation agency for real-time monitoring and
further management of water quality.
PMID- 29334392
TI - Control of collagen gel mechanical properties through manipulation of gelation
conditions near the sol-gel transition.
AB - The ability to control the mechanical properties of cell culture environments is
known to influence cell morphology, motility, invasion and differentiation. The
present work shows that it is possible to control the mechanical properties of
collagen gels by manipulating gelation conditions near the sol gel transition.
This manipulation is accomplished by performing gelation in two stages at
different temperatures. The mechanical properties of the gel are found to be
strongly dependent on the duration and temperature of the first stage. In the
second stage the system is quickly depleted of free collagen which self assembles
into a highly branched network characteristic of gelation at the higher
temperature (37 degrees C). An important aspect of the present work is the use
of advanced rheometric techniques to assess the transition point between
viscoelastic liquid and viscoelastic solid behaviour which occurs upon
establishment of a sample spanning network at the gel point. The gel time at the
stage I temperature is found to indicate the minimum time that the gelling
collagen sample must spend under stage I conditions before the two stage gelation
procedure generates an enhancement of mechanical properties. Further, the
Fractional Maxwell Model is found to provide an excellent description of the time
dependent mechanical properties of the mature collagen gels.
PMID- 29334393
TI - Facile fabrication and characterization of two-dimensional bismuth(iii) sulfide
nanosheets for high-performance photodetector applications under ambient
conditions.
AB - Two-dimensional (2D) bismuth(iii) sulfide (Bi2S3) nanosheets as non-toxic
graphene-like nanomaterials were successfully fabricated by a facile liquid phase
exfoliation (LPE) method. A robust photodetector employing a Bi2S3 nanosheet film
has been fabricated for the first time via a facile fabrication process on an ITO
coated glass. UV-Vis and Raman spectroscopy techniques were carried out and they
confirmed the inherent optical and physical properties of Bi2S3 nanosheets.
Photoelectrochemical (PEC) measurements demonstrate that a significantly higher
photocurrent density (42 MUA cm-2) and enhanced photoresponsivity (210 MUA W-1),
at a lower bias potential in alkaline solution, of the Bi2S3 nanosheet-based
photodetector are achieved, compared with those of other 2D nanomaterial-based
photodetectors under light irradiation. Furthermore, the as-prepared Bi2S3
nanosheet-based photodetector not only exhibits an appropriate capacity of self
driven broadband and high-performance photoresponse but also displays strong long
term stability of the ON/OFF switching behaviour without any external protection
in alkaline solutions. Because of facile synthesis via a LPE method, a higher
photocurrent density and photoresponsivity, self-driven performance and long-term
stability of the Bi2S3 nanosheet-based photodetector at a lower bias potential in
alkaline solutions, the present work can provide fundamental acknowledgement of
the high performance of this new kind of PEC-type 2D nanosheet-based
photodetector.
PMID- 29334394
TI - Substitution of the laser borane anti-B18H22 with pyridine: a structural and
photophysical study of some unusually structured macropolyhedral boron hydrides.
AB - Reaction of anti-B18H221 with pyridine in neutral solvents gives sparingly
soluble B16H18-3',8'-Py23a as the major product (ca. 53%) and B18H20-6',9'-Py22
(ca. 15%) as the minor product, with small quantities of B18H20-8'-Py 4 (ca. 1%)
also being formed. The three new compounds 2, 3a and 4 are characterized by
single-crystal X-ray diffraction analyses and by multinuclear multiple-resonance
NMR spectroscopy. Compound 2 is of ten-vertex nido:ten-vertex arachno two-atoms
in-common architecture, long postulated for a species with borons-only cluster
constitution, but previously elusive. Compound 3a is of unprecedented ten-vertex
nido:eight-vertex arachno two-atoms-in-common architecture. The single-crystal X
ray diffraction analysis for the picoline derivative B16H18(NC5H4Me)23b,
similarly obtained, is also presented. B18H20Py 4 is also previously unreported
but is of known ten-vertex nido:ten-vertex nido two-atoms-in-common architecture
of anti configuration, but now with the pyridine ligand positioned differently to
other reported examples of B18H20L compounds. Factors behind the remarkably low
solubility of 3a and 3b are elucidated in terms of electrostatic potential (ESP)
calculations, polarity, and van der Waals complementarities. In view of
contemporary developing high interest in the fluorescent properties of
macropolyhedral boron-containing species, a detailed assessment of the
photophysical characteristics of 3a and 4 is also presented. In contrast to the
thermochromic fluorescence of 2 (from 620 nm brick-red at room temperature to 585
nm yellow at 8 K, quantum yield 0.15), compound 3a is only weakly phosphorescent
in the yellow region (590 nm, quantum yield 0.01), whereas compound 4 exhibits no
luminescence. The far more photoactive nature of compound 2 is associated with S1
excited-state minima structures that differ from each other only by the relative
rotational positions of the pyridine substituents on its disubstituted ten-vertex
{arachno-B10Py2}-subcluster. The wavelength and relative intensity of
fluorescence from these structures depends on the rotational positions of the
pyridine ligands, which in turn are influenced by temperature and/or rotational
inhibition in the solid-state.
PMID- 29334395
TI - Probing the geometry of copper and silver adatoms on magnetite: quantitative
experiment versus theory.
AB - Accurately modelling the structure of a catalyst is a fundamental prerequisite
for correctly predicting reaction pathways, but a lack of clear experimental
benchmarks makes it difficult to determine the optimal theoretical approach.
Here, we utilize the normal incidence X-ray standing wave (NIXSW) technique to
precisely determine the three dimensional geometry of Ag1 and Cu1 adatoms on
Fe3O4(001). Both adatoms occupy bulk-continuation cation sites, but with a
markedly different height above the surface (0.43 +/- 0.03 A (Cu1) and 0.96 +/-
0.03 A (Ag1)). HSE-based calculations accurately predict the experimental
geometry, but the more common PBE + U and PBEsol + U approaches perform poorly.
PMID- 29334396
TI - Towards the continuous production of Pt-based heterogeneous catalysts using
microfluidic systems.
AB - The continuous production of Pt-based heterogeneous catalysts based on ultra
small (<2 nm) noble metal nanoparticles deposited on mesoporous ordered silica
and their catalytic activity in VOC abatement are here reported. Microfluidic
reactors can be used not only to enable the fast and controlled production of
ultra-small Pt nanoparticles (NPs), but also alloyed NPs including PtPd, PtRu and
PtRh can be formed in short residence times (between 60 s and 5 min). A novel
continuous and homogeneous loading of these catalytic NPs on SBA-15 used as a
mesoporous support is also here reported. This procedure eases the NP loading and
minimizes washing post-treatments. A 12-fold decrease in the synthesis time was
obtained when using this microfluidic reactor compared to the traditional batch
production of Pt NPs. Microflow and batch type reactors yielded a Pt precursor
conversion to generate Pt NPs with a 90% and 85% yield, respectively. Under the
same conditions, the productivity of the microfluidic system (27 mg Pt NPs per h)
was twice the one achieved in the conventional batch type reactor. The catalytic
performance of the supported catalysts separately prepared by microfluidics and
by conventional impregnation under the same conditions and with the same noble
metal loading was also compared in the n-hexane abatement as a model of VOCs.
Both catalysts were active in the VOC oxidation reaction but a 95% reduction in
the catalyst synthesis time was obtained when using the catalysts produced in the
microfluidic platform. For this reaction a long-term activity test was
successfully carried out at 175 degrees C during 30 h on stream using the
heterogeneous catalyst prepared by using the flow reactor.
PMID- 29334398
TI - Formation of shelf stable Pickering high internal phase emulsions (HIPE) through
the inclusion of whey protein microgels.
AB - High internal phase emulsions (HIPE) prepared using whey protein microgels (WPMs)
as a surfactant were demonstrated to have substantially higher stability than
HIPEs prepared using similar loadings of non-gelled whey protein isolate (WPI) or
Tween 20. Microgel colloids were prepared from WPI solutions by heat treatment at
85 degrees C in a narrow pH range (5.8-6.0) to particle sizes of approximately
90, 160 and 350 nm in diameter. zeta-potentials of the WPM increased in
negativity with decreasing particle size from -7.4 +/- 2.5 down to -21.1 +/- 0.9
at 90 nm. All WPMs conferred high stability to corn oil based HIPE when used as
an emulsifier. Light microscopy and cryo-scanning electron microscopy showed that
both increasing WPM concentration and decreasing WPM particle size produced
increasingly smaller and more hexagonally shaped corn oil emulsion droplets; WPI
and Tween 20 based HIPE droplets were generally smaller and spherical in shape.
The HIPE (75% w/w corn oil) produced with 1% (w/w) WPM as an emulsifier showed
stability through 6 months storage at 4 degrees C at all WPM sizes tested, while
the HIPE prepared with 1% (w/w) WPI or Tween 20 exhibited significant creaming.
WPM and WPI based HIPE both showed thermal stability at 70 degrees C and 95
degrees C while the heating of Tween 20 based HIPE resulted in droplet
coalescence and oil-phase separation. HIPE production with WPMs significantly
improved the viscoelastic properties of the HIPE, imparting drastic increases in
yield stress, critical stress, complex modulus and elastic modulus over HIPE
prepared with WPI or Tween 20. The more rigid rheology of the WPM HIPE indicated
by these data is likely the primary mechanism driving the improved stability of
these emulsions.
PMID- 29334397
TI - Recombinant phosphatidylserine-binding nanobodies for targeting of extracellular
vesicles to tumor cells: a plug-and-play approach.
AB - Extracellular vesicles (EVs) are increasingly being recognized as candidate drug
delivery systems due to their ability to functionally transfer biological cargo
between cells. However, manipulation of targeting properties of EVs through
engineering of the producer cells can be challenging and time-consuming. As a
novel approach to confer tumor targeting properties to isolated EVs, we generated
recombinant fusion proteins of nanobodies against the epidermal growth factor
receptor (EGFR) fused to phosphatidylserine (PS)-binding domains of lactadherin
(C1C2). C1C2-nanobody fusion proteins were expressed in HEK293 cells and isolated
from culture medium with near-complete purity as determined by SDS-PAGE. Fusion
proteins specifically bound PS and showed no affinity for other common EV
membrane lipids. Furthermore, C1C2 fused to anti-EGFR nanobodies (EGa1-C1C2)
bound EGFR with high affinity and competed with binding of its natural ligand
EGF, as opposed to C1C2 fused to non-targeting control nanobodies (R2-C1C2). Both
proteins readily self-associated onto membranes of EVs derived from erythrocytes
and Neuro2A cells without affecting EV size and integrity. EV-bound R2-C1C2 did
not influence EV-cell interactions, whereas EV-bound EGa1-C1C2 dose-dependently
enhanced specific binding and uptake of EVs by EGFR-overexpressing tumor cells.
In conclusion, we developed a novel strategy to efficiently and universally
confer tumor targeting properties to PS-exposing EVs after their isolation,
without affecting EV characteristics, circumventing the need to modify EV
secreting cells. This strategy may also be employed to decorate EVs with other
moieties, including imaging probes or therapeutic proteins.
PMID- 29334399
TI - Chondrocyte burst promotes space for mineral expansion.
AB - Analysis of tissue development from multidisciplinary approaches can result in
more integrative biological findings, and can eventually allow the development of
more effective bioengineering methods. In this study, we analyzed the initial
steps of mineral formation during secondary ossification of mouse femur based on
biological and bioengineering approaches. We first found that some chondrocytes
burst near the mineralized area. External factors that could trigger chondrocyte
burst were then investigated. Chondrocyte burst was shown to be modulated by
mechanical and osmotic pressure. A hypotonic solution, as well as mechanical
stress, significantly induced chondrocyte burst. We further hypothesized that
chondrocyte burst could be associated with space-making for mineral expansion. In
fact, ex vivo culture of femur epiphysis in hypotonic conditions, or under
mechanical pressure, enhanced mineral formation, compared to normal culture
conditions. Additionally, the effect of mechanical pressure on bone formation in
vivo was investigated by immobilization of mouse lower limbs to decrease the body
pressure onto the joints. The results showed that limb immobilization suppressed
bone formation. Together, these results suggest chondrocyte burst as a novel fate
of chondrocytes, and that manipulation of chondrocyte burst with external mechano
chemical stimuli could be an additional approach for cartilage and bone tissue
engineering.
PMID- 29334400
TI - Oolong tea and LR-White resin: a new method of plant sample preparation for
transmission electron microscopy.
AB - Simplifying sample processing, shortening the sample preparation time, and
adjusting procedures to suitable for new health and safety regulations, these
issues are the current challenges which electron microscopic examinations need to
face. In order to resolve these problems, new plant tissue sample processing
protocols for transmission electron microscopy should be developed. In the
present study, we chose the LR-White resin-assisted processing protocol for the
ultrastructural observation of different types of plant tissues. Moreover, we
explored Oolong tea extract (OTE) as a substitute for UA in staining ultrathin
sections of plant samples. The results revealed that there was no significant
difference between the OTE double staining method and the traditional double
staining method. Furthermore, in some organelles, such as mitochondria in root
cells of tomatoes and chloroplast in leaf cells of watermelons, the OTE double
staining method achieved little better results than the traditional double
staining method. Therefore, OTE demonstrated good potentials in replacing UA as a
counterstain on ultrathin sections. In addition, sample preparation time was
significantly shortened and simplified using LR-White resin. This novel protocol
reduced the time for preparing plant samples, and hazardous reagents in
traditional method (acetone and UA) were also replaced by less toxic ones
(ethanol and OTE).
PMID- 29334401
TI - Unearthing belowground bud banks in fire-prone ecosystems.
AB - Despite long-time awareness of the importance of the location of buds in plant
biology, research on belowground bud banks has been scant. Terms such as
lignotuber, xylopodium and sobole, all referring to belowground bud-bearing
structures, are used inconsistently in the literature. Because soil efficiently
insulates meristems from the heat of fire, concealing buds below ground provides
fitness benefits in fire-prone ecosystems. Thus, in these ecosystems, there is a
remarkable diversity of bud-bearing structures. There are at least six locations
where belowground buds are stored: roots, root crown, rhizomes, woody burls,
fleshy swellings and belowground caudexes. These support many morphologically
distinct organs. Given their history and function, these organs may be divided
into three groups: those that originated in the early history of plants and that
currently are widespread (bud-bearing roots and root crowns); those that also
originated early and have spread mainly among ferns and monocots (nonwoody
rhizomes and a wide range of fleshy underground swellings); and those that
originated later in history and are strictly tied to fire-prone ecosystems (woody
rhizomes, lignotubers and xylopodia). Recognizing the diversity of belowground
bud banks is the starting point for understanding the many evolutionary pathways
available for responding to severe recurrent disturbances.
PMID- 29334402
TI - Noninvasive reconstruction of placental methylome from maternal plasma DNA:
Potential for prenatal testing and monitoring.
AB - OBJECTIVE: During human pregnancy, the DNA methylation of placental tissue is
highly relevant to the normal growth and development of the fetus; therefore,
methylomic analysis of the placental tissue possesses high research and clinical
value in prenatal testing and monitoring. Thus, our aim is to develop an approach
for reconstruction of the placental methylome, which should be completely
noninvasive and achieve high accuracy and resolution. RESULTS: We propose a novel
size-based algorithm, FEtal MEthylome Reconstructor (FEMER), to noninvasively
reconstruct the placental methylome by genomewide bisulfite sequencing and size
based analysis of maternal plasma DNA. By applying FEMER on a real clinical
dataset, we demonstrate that FEMER achieves both high accuracy and resolution,
thus provides a high-quality view of the placental methylome from maternal plasma
DNA. FEtal MEthylome Reconstructor could also predict the DNA methylation profile
of CpG islands with high accuracy, thus shows potential in monitoring of key
genes involved in placental/fetal development. Source code and testing datasets
for FEMER are available at http://sunlab.cpy.cuhk.edu.hk/FEMER/. CONCLUSION:
FEtal MEthylome Reconstructor could enhance the noninvasive fetal/placental
methylomic analysis and facilitate its application in prenatal testing and
monitoring.
PMID- 29334403
TI - Soft tissue volume gain around dental implants using autogenous subepithelial
connective tissue grafts harvested from the lateral palate or tuberosity area. A
randomized controlled clinical study.
AB - AIM: To compare the soft tissue volume gain (VG) around single tooth implants
with subepithelial connective tissue graft (SCTG) from either the lateral palate
(LP) or from the tuberosity area (TA). METHODS: Thirty-two patients with 36
implants with buccal volume deficiencies were randomly assigned to receive SCTG
from LP (control group/CG) or TA (test group/TG). Clinical parameters were
recorded. VG was evaluated by stereolithography (STL) image superimposition of
two intraoral scans (baseline/BL and 3 months after surgery/FU-3). Descriptive
analysis was performed for both groups, and for comparisons, Mann-Whitney U test
was used. RESULTS: In terms of VG values, no statistically significant
differences were observed except for values at 6 and 7 mm apically to the healing
abutment which favoured the TG. Mean values were 0.69 +/- 0.23 mm for CG while TG
obtained 0.79 +/- 0.10 mm (p = .64). Regarding Keratinized tissue (KT) width
statistical significant differences were found favouring TG, which obtained a
gain of 0.83 +/- 0.61 mm compared with 0.22 +/- 0.48 mm for CG (p = .009). Pink
esthetic scores resulted in mean values of 10.07 +/- 2.19 for the CG, while TG
obtained 9.15 +/- 2.34. CONCLUSIONS: Both procedures were effective in increasing
soft tissue volume with no statistically significant differences. A longer follow
up is needed to confirm or refute these results.
PMID- 29334404
TI - Special Issue "Chiroptical Spectroscopy: Instrumentation, Experimental Aspects
and Applications" in memory of Ettore Castiglioni.
PMID- 29334405
TI - High-resolution dental magnetic resonance imaging for planning palatal graft
surgery-a clinical pilot study.
AB - AIM: To evaluate whether high-resolution, non-contrast-enhanced dental magnetic
resonance imaging (MRI) can be used for accurate determination of palatal
masticatory mucosa thickness (PMMT) and to locate the greater palatal artery
(GPA). MATERIALS AND METHODS: In five volunteers (four males, one female; mean
age 30.2 +/- 0.4 years), two independent raters measured PMMT by use of dental
MRI in 180 positions. For comparison, clinical bone sounding was performed. The
GPA was identified in time-of-flight (TOF) angiography and MSVAT-SPACE-prototype
sequence. Intra- and inter-observer agreement for MRI measurements, agreement
between MRI and bone sounding were analysed by intra-class correlation
coefficient (ICC) and Cohen's kappa (kappa). RESULTS: Reliability of dental MRI
measurements was high (intra-observer-ICC 0.962; inter-observer ICC 0.959).
Agreement of MRI measurements with bone sounding was moderate (ICC 0.744), and
the GPA could be identified in 60% of measurement points using the TOF
angiography alone and in 85% with additional information of the MSVAT-SPACE. Good
intra-observer agreement was observed for GPA identification (kappa: 0.778).
CONCLUSION: Palatal masticatory mucosa thickness measured by high-resolution, non
contrast enhanced dental MRI is comparable with that obtained by bone sounding.
Dental MRI enables reliable, non-invasive and radiation-free planning of palatal
tissue harvesting and can also be used for location of the GPA at 85% of
measurement points, which might help reduce complications during surgery.
PMID- 29334407
TI - Chiral separation of novel iminonaringenin derivatives.
AB - A series of 4-iminonaringenin derivatives 2-6 have been prepared in good overall
yields from a condensation reaction between naringenin and primary amines. The
structures of all products were confirmed by ultraviolet, infrared, proton
nuclear magnetic resonance, and carbon-13 nuclear magnetic resonance
spectroscopic techniques. These derivatives were analyzed by high-performance
liquid chromatography using polysaccharide-based chiral stationary phases,
namely, Chiralpak IB and Chiralcel OD, using various mobile phases. 2-Propanol
showed a high enantioselectivity for naringin and its derivatives using achiral
column containing immobilized polysaccharides (Chiralpak IB).
PMID- 29334406
TI - Dasatinib-induced pulmonary arterial hypertension.
AB - Drug-induced (group 1) pulmonary hypertension (PH) is an important subgroup of PH
involving dasatinib as a likely related agent, which is a second-generation
tyrosine kinase inhibitor (TKI) used in the treatment of chronic myeloid
leukaemia (CML). The mechanism of dasatinib-induced pulmonary arterial
hypertension (PAH) is unclear. However, the occurrence of PAH with late onset in
CML patients suggests a chronic pathological mechanism with an insidious onset
rather than an acute inflammatory or cardiac aetiology. Dasatinib has a broader
effect than other TKIs; the major known difference between dasatinib and other
TKIs is the additional inhibition of Src family kinases. Therefore, Src
inhibition was thought to play a role in the development of dasatinib-induced
PAH. However, recently, it was also speculated that chronic dasatinib therapy may
cause pulmonary endothelial damage, attenuate hypoxic pulmonary vasoconstriction
responses and increase susceptibility to PAH independently of the Src family
kinase-induced mechanism. Dasatinib-induced PAH usually seems to be reversible
with the cessation of the drug, and sometimes with PAH-specific treatment
strategies. Transthoracic echocardiography can be recommended as a routine
screening prior to dasatinib initiation, and this non-invasive procedure can be
utilized in patients having signs and symptoms attributable to PAH during
dasatinib treatment.
PMID- 29334408
TI - Effects of metalaxyl enantiomers stress on root activity and leaf antioxidant
enzyme activities in tobacco seedlings.
AB - The objective of this experiment was to study the effects of metalaxyl
enantiomers on the activity of roots and antioxidative enzymes in tobacco
seedlings. Water culture experiment was conducted to analyze the effects of
different concentrations of metalaxyl enantiomers (30 and 10 mg L-1 ) on root
activity and leaf superoxide dismutase (SOD), peroxidase (POD), and catalase
(CAT) activities and malondialdehyde (MDA) content of tobacco seedlings. The
results showed that metalaxyl significantly inhibited root activity and
significantly improved leaf SOD, POD, and CAT activities and MDA content. A
better physiological response in tobacco seedlings was observed at 30 mg L-1 than
at 10 mg L-1 metalaxyl. The stereoselectivity for different enantiomers had no
obvious effect on root activity and the leaf POD activity, but it affected
significantly the SOD and CAT activities and MDA content. The SOD activity was
promoted more by R-enantiomer than by S-enantiomer at 30 mg L-1 metalaxyl, and
the same effect was observed on CAT activity from the beginning to the end of the
stress period. The MDA content under the stress by R-enantiomer was higher than
that under the stress by S-enantiomer at 10 mg L-1 metalaxyl.
PMID- 29334409
TI - Climate-driven mitochondrial selection: A test in Australian songbirds.
AB - Diversifying selection between populations that inhabit different environments
can promote lineage divergence within species and ultimately drive speciation.
The mitochondrial genome (mitogenome) encodes essential proteins of the oxidative
phosphorylation (OXPHOS) system and can be a strong target for climate-driven
selection (i.e., associated with inhabiting different climates). We investigated
whether Pleistocene climate changes drove mitochondrial selection and evolution
within Australian birds. First, using phylogeographic analyses of the
mitochondrial ND2 gene for 17 songbird species, we identified mitochondrial
clades (mitolineages). Second, using distance-based redundancy analyses, we
tested whether climate predicts variation in intraspecific genetic divergence
beyond that explained by geographic distances and geographic position. Third, we
analysed 41 complete mitogenome sequences representing each mitolineage of 17
species using codon models in a phylogenetic framework and a biochemical approach
to identify signals of selection on OXPHOS protein-coding genes and test for
parallel selection in mitolineages of different species existing in similar
climates. Of 17 species examined, 13 had multiple mitolineages (range: 2-6).
Climate was a significant predictor of mitochondrial variation in eight species.
At least two amino acid replacements in OXPHOS complex I could have evolved under
positive selection in specific mitolineages of two species. Protein homology
modelling showed one of these to be in the loop region of the ND6 protein channel
and the other in the functionally critical helix HL region of ND5. These findings
call for direct tests of the functional and evolutionary significance of
mitochondrial protein candidates for climate-associated selection.
PMID- 29334410
TI - Selective Binding and Precipitation of Cesium Ions from Aqueous Solutions: A Size
Driven Supramolecular Reaction.
AB - The nuclear disasters of Chernobyl and Fukushima presented an urgent need for
finding solutions to treatment of radioactive wastes. Among the by-products of
nuclear fission is radioactive 137 Cs, which evokes an environmental hazard due
to its long half-life (>30 years) and high solubility in water. In this work, a
water-soluble organic ligand, readily obtained from alloxan and 1,3,5
benzenetriol, has been found to selectively bind and precipitate Cs+ ions from
aqueous solutions. The special rigid structure of the ligand, which consists of a
"tripodal" carbonyl base above and below an aromatic plane, contributes to the
size-driven selectivity towards the large Cs+ ions and the formation of a giant,
insoluble supramolecular complex. In addition to the low costs of the ligand,
high yields and effectiveness in precipitating Cs+ ions, the Cs-complex revealed
a high endurance to continuous doses of gamma-radiation, increasing its potential
to act as a precipitating agent for 137 Cs.
PMID- 29334411
TI - Nickel-Catalyzed C-S Bond Formation via Decarbonylative Thioetherification of
Esters, Amides and Intramolecular Recombination Fragment Coupling of Thioesters.
AB - A nickel catalyzed cross-coupling protocol for the straightforward C-S bond
formation has been developed. Various mercaptans and a wide range of ester and
amide substrates bearing various substituents were tolerated in this process
which afforded products in good to excellent yields. Furthermore, an
intramolecular protocol for the synthesis of thioethers starting from thioesters
has been developed. The utility of this protocol has been demonstrated in a new
synthetic protocol of benzothiophene.
PMID- 29334412
TI - Stallion semen quality depends on major histocompatibility complex matching to
teaser mare.
AB - The major histocompatibility complex (MHC) has repeatedly been found to influence
mate choice of vertebrates, with MHC-dissimilar mates typically being preferred
over MHC-similar mates. We used horses (Equus caballus) to test whether MHC
matching also affects male investment into ejaculates after short exposure to a
female. Semen characteristics varied much among stallions. Controlling for this
variance with a full-factorial within-subject experimental design, we found that
a short exposure to an MHC-dissimilar mare enhanced male plasma testosterone and
led to ejaculates with elevated sperm numbers as compared to exposure to an MHC
similar mare. Sperm velocity seemed not affected by the treatment. Overall
genetic similarity between stallions and mares (determined from polymorphic
microsatellites on 20 different chromosomes) played no significant role here. The
MHC type of the teaser mare also affected characteristics of cold-stored sperm
after 24 and 48 hr. As expected from ejaculate economics, sperm viability was
elevated after exposure to an MHC-dissimilar mare. However, oxidative stress and
the percentage of sperm with a high DNA fragmentation were mostly increased after
exposure to an MHC-dissimilar mare, depending also on whether the teaser mare was
in oestrous or not. We conclude that males can quickly adjust ejaculate quality
relative to a female's MHC, and that this male reaction to the social environment
can also affect important characteristics of cold-stored semen.
PMID- 29334413
TI - Features of Auxiliaries That Enable Native Chemical Ligation beyond Glycine and
Cleavage via Radical Fragmentation.
AB - Native chemical ligation (NCL) is an invaluable tool in the total chemical
synthesis of proteins. Ligation auxiliaries overcome the requirement for
cysteine. However, the reported auxiliaries remained limited to glycine
containing ligation sites and the acidic conditions applied for cleavage of the
typically applied N-benzyl-type linkages promote side reactions. With the aim to
improve upon both ligation and cleavage, we systematically investigated
alternative ligation scaffolds that challenge the N-benzyl dogma. The study
revealed that auxiliary-mediated peptide couplings are fastest when the ligation
proceeds via 5-membered rather than 6-membered rings. Substituents in alpha
position of the amine shall be avoided. We observed, perhaps surprisingly, that
additional beta-substituents accelerated the ligation conferred by the beta
mercaptoethyl scaffold. We also describe a potentially general means to remove
ligation auxiliaries by treatment with an aqueous solution of
triscarboxyethylphosphine (TCEP) and morpholine at pH 8.5. NMR analysis of a 13 C
labeled auxiliary showed that cleavage most likely proceeds through a radical
triggered oxidative fragmentation. High ligation rates provided by beta
substituted 2-mercaptoethyl scaffolds, their facile introduction as well as the
mildness of the cleavage reaction are attractive features for protein synthesis
beyond cysteine and glycine ligation sites.
PMID- 29334414
TI - Cryptic species as a window into the paradigm shift of the species concept.
AB - The species concept is the cornerstone of biodiversity science, and any paradigm
shift in the delimitation of species affects many research fields. Many
biologists now are embracing a new "species" paradigm as separately evolving
populations using different delimitation criteria. Individual criteria can emerge
during different periods of speciation; some may never evolve. As such, a
paradigm shift in the species concept relates to this inherent heterogeneity in
the speciation process and species category-which is fundamentally overlooked in
biodiversity research. Cryptic species fall within this paradigm shift: they are
continuously being reported from diverse animal phyla but are poorly considered
in current tests of ecological and evolutionary theory. The aim of this review is
to integrate cryptic species in biodiversity science. In the first section, we
address that the absence of morphological diversification is an evolutionary
phenomenon, a "process" counterpart to the long-studied mechanisms of
morphological diversification. In the next section regarding taxonomy, we show
that molecular delimitation of cryptic species is heavily biased towards distance
based methods. We also stress the importance of formally naming of cryptic
species for better integration into research fields that use species as units of
analysis. Finally, we show that incorporating cryptic species leads to novel
insights regarding biodiversity patterns and processes, including large-scale
biodiversity assessments, geographic variation in species distribution and
species coexistence. It is time for incorporating multicriteria species
approaches aiming to understand speciation across space and taxa, thus allowing
integration into biodiversity conservation while accommodating for species
uncertainty.
PMID- 29334415
TI - Early burst in body size evolution is uncoupled from species diversification in
diving beetles (Dytiscidae).
AB - Changes in morphology are often thought to be linked to changes in species
diversification, which is expected to leave a signal of early burst (EB) in
phenotypic traits. However, such signal is rarely recovered in empirical
phylogenies, even for groups with well-known adaptive radiation. Using a
comprehensive phylogenetic approach in Dytiscidae, which harbours ~4,300 species
with as much as 50-fold variation in body size among them, we ask whether pattern
of species diversification correlates with morphological evolution. Additionally,
we test whether the large variation in body size is linked to habitat preference
and whether the latter influences species turnover. We found, in sharp contrast
to most animal groups, that Dytiscidae body size evolution follows an early-burst
model with subsequent high phylogenetic conservatism. However, we found no
evidence for associated shifts in species diversification, which point to an
uncoupled evolution of morphology and species diversification. We recovered the
ancestral habitat of Dytiscidae as lentic (standing water), with many transitions
to lotic habitat (running water) that are concomitant to a decrease in body size.
Finally, we found no evidence for difference in net diversification rates between
habitats nor difference in turnover in lentic and lotic species. This result,
together with recent findings in dragonflies, contrasts with some theoretical
expectations of the habitat stability hypothesis. Thus, a thorough reassessment
of the impact of dispersal, gene flow and range size on the speciation process is
needed to fully encompass the evolutionary consequences of the lentic-lotic
divide for freshwater fauna.
PMID- 29334416
TI - Investigating causal associations between use of nicotine, alcohol, caffeine and
cannabis: a two-sample bidirectional Mendelian randomization study.
AB - BACKGROUND AND AIMS: Epidemiological studies consistently show co-occurrence of
use of different addictive substances. Whether these associations are causal or
due to overlapping underlying influences remains an important question in
addiction research. Methodological advances have made it possible to use
published genetic associations to infer causal relationships between phenotypes.
In this exploratory study, we used Mendelian randomization (MR) to examine the
causality of well-established associations between nicotine, alcohol, caffeine
and cannabis use. METHODS: Two-sample MR was employed to estimate bidirectional
causal effects between four addictive substances: nicotine (smoking initiation
and cigarettes smoked per day), caffeine (cups of coffee per day), alcohol (units
per week) and cannabis (initiation). Based on existing genome-wide association
results we selected genetic variants associated with the exposure measure as an
instrument to estimate causal effects. Where possible we applied sensitivity
analyses (MR-Egger and weighted median) more robust to horizontal pleiotropy.
RESULTS: Most MR tests did not reveal causal associations. There was some weak
evidence for a causal positive effect of genetically instrumented alcohol use on
smoking initiation and of cigarettes per day on caffeine use, but these were not
supported by the sensitivity analyses. There was also some suggestive evidence
for a positive effect of alcohol use on caffeine use (only with MR-Egger) and
smoking initiation on cannabis initiation (only with weighted median). None of
the suggestive causal associations survived corrections for multiple testing.
CONCLUSIONS: Two-sample Mendelian randomization analyses found little evidence
for causal relationships between nicotine, alcohol, caffeine and cannabis use.
PMID- 29334417
TI - Combining allele frequency and tree-based approaches improves phylogeographic
inference from natural history collections.
AB - Model selection approaches in phylogeography have allowed researchers to evaluate
the support for competing demographic histories, which provides a mode of
inference and a measure of uncertainty in understanding climatic and spatial
influences on intraspecific diversity. Here, to rank all models in the comparison
set and determine what proportion of the total support the top-ranked model
garners, we conduct model selection using two analytical approaches-allele
frequency-based, implemented in fastsimcoal2, and gene tree-based, implemented in
phrapl. We then expand this model selection framework by including an assessment
of absolute fit of the models to the data. For this, we utilize DNA isolated from
existing natural history collections that span the distribution of red alder
(Alnus rubra) in the Pacific Northwest of North America to generate genomic data
for the evaluation of 13 demographic scenarios. The quality of DNA recovered from
herbarium specimen leaf tissue was assessed for its utility and effectiveness in
demographic model selection, specifically in the two approaches mentioned. We
present strong support for the use of herbarium tissue in the generation of
genomic DNA, albeit with the inclusion of additional quality control checks prior
to library preparation and analyses with multiple approaches that incorporate
various data. Analyses with allele frequency spectra and gene trees predominantly
support A. rubra having experienced an ancient vicariance event with intermittent
and frequent gene flow between the disjunct populations. Additionally, the data
consistently fit the most frequently selected model, corroborating the model
selection techniques. Finally, these results suggest that the A. rubra disjunct
populations do not represent separate species.
PMID- 29334418
TI - Antimicrobial and stress responses to increased temperature and bacterial
pathogen challenge in the holobiont of a reef-building coral.
AB - Global increases in coral disease prevalence have been linked to ocean warming
through changes in coral-associated bacterial communities, pathogen virulence and
immune system function. However, the interactive effects of temperature and
pathogens on the coral holobiont are poorly understood. Here, we assessed three
compartments of the holobiont (host, Symbiodinium and bacterial community) of the
coral Montipora aequituberculata challenged with the pathogen Vibrio
coralliilyticus and the commensal bacterium Oceanospirillales sp. under ambient
(27 degrees C) and elevated (29.5 and 32 degrees C) seawater temperatures. Few
visual signs of bleaching and disease development were apparent in any of the
treatments, but responses were detected in the holobiont compartments. V.
coralliilyticus acted synergistically and negatively impacted the photochemical
efficiency of Symbiodinium at 32 degrees C, while Oceanospirillales had no
significant effect on photosynthetic efficiency. The coral, however, exhibited a
minor response to the bacterial challenges, with the response towards V.
coralliilyticus being significantly more pronounced, and involving the
prophenoloxidase-activating system and multiple immune system-related genes.
Elevated seawater temperatures did not induce shifts in the coral-associated
bacterial community, but caused significant gene expression modulation in both
Symbiodinium and the coral host. While Symbiodinium exhibited an antiviral
response and upregulated stress response genes, M. aequituberculata showed
regulation of genes involved in stress and innate immune response processes,
including immune and cytokine receptor signalling, the complement system, immune
cell activation and phagocytosis, as well as molecular chaperones. These
observations show that M. aequituberculata is capable of maintaining a stable
bacterial community under elevated seawater temperatures and thereby contributes
to preventing disease development.
PMID- 29334419
TI - A Metallo Pro-Drug to Target CuII in the Context of Alzheimer's Disease.
AB - Alzheimer's disease and oxidative stress are connected. In the present
communication, we report the use of a MnII -based superoxide dismutase (SOD)
mimic ([MnII (L)]+ , 1+ ) as a pro-drug candidate to target CuII -associated
events, namely, CuII -induced formation of reactive oxygen species (ROS) and
modulation of the amyloid-beta (Abeta) peptide aggregation. Complex 1+ is able to
remove CuII from Abeta, stop ROS and prevent alteration of Abeta aggregation as
would do the corresponding free ligand LH. Using 1+ instead of LH in further
biological applications would have the double advantage to avoid the cell
toxicity of LH and to benefit from its proved SOD-like activity.
PMID- 29334420
TI - Copper-Catalyzed Regioselective Cleavage of C-X and C-H Bonds: A Strategy for
Sulfur Dioxide Fixation.
AB - The first example of direct fixation of sulfur dioxide between heteroaryls and
aryl halides has been developed via copper-catalyzed regioselective cleavage of C
X and C-H bonds under base-free and ligand-free conditions by using DABSO (1,4
diazabicyclo[2.2.2]octane bis(sulfur dioxide)) as a solid and bench-stable sulfur
dioxide surrogate. This mild protocol results in double C-S bond-forming
reactions from simple precursors in the absence of prefunctionalized
organometallic reagents, arenediazonium salts, and iodonium salts which extends
the still limited number of sulfur dioxide fixation strategies.
PMID- 29334421
TI - A Survey of tooth morphology teaching methods employed in the United Kingdom and
Ireland.
AB - BACKGROUND: Tooth morphology is a central component of the dental curriculum and
is applicable to all dental specialities. Traditional teaching methods are being
supplemented with innovative strategies to tailor teaching and accommodate the
learning styles of the recent generation of students. METHODS: An online survey
was compiled and distributed to the staff involved in teaching tooth morphology
in the United Kingdom and Ireland to assess the importance of tooth morphology in
the dentistry curriculum and the methodologies employed in teaching. RESULTS: The
results of the survey show that tooth morphology constitutes a small module in
the dental curriculum. It is taught in the first 2 years of the dental curriculum
but is applicable in the clinical years and throughout the dental career.
Traditional teaching methods, lecture and practical, are being augmented with
innovative teaching including e-learning via virtual learning environment, tooth
atlas and e-books leading to blended learning. The majority of the schools teach
both normal dental anatomy and morphologic variations of dental anatomy and
utilise plastic teeth for practical and examination purposes. Learning the 3D
aspects of tooth morphology was deemed important by most of the respondents who
also agreed that tooth morphology is a difficult topic for the students.
CONCLUSION: Despite being core to the dental curriculum, overall minimal time is
dedicated to the delivery of tooth morphology, creating a reliance on the student
to learn the material. New forms of delivery including computer-assisted learning
tools should help sustain learning and previously acquired knowledge.
PMID- 29334422
TI - Psychosocial risks at the workplace and quality of life in cancer survivors in
employment.
PMID- 29334423
TI - Mechanochemical Activation of Iron Cyano Complexes: A Prebiotic Impact Scenario
for the Synthesis of alpha-Amino Acid Derivatives.
AB - Mechanochemical activation of iron cyano complexes by ball milling results in the
formation of HCN, which can be trapped and incorporated into alpha-aminonitriles.
This prebiotic impact scenario can be extended by mechanochemically transforming
the resulting alpha-aminonitriles into alpha-amino amides using a chemical route
related to early Earth conditions.
PMID- 29334424
TI - In Vivo EPR Characterization of Semi-Synthetic [FeFe] Hydrogenases.
AB - EPR spectroscopy reveals the formation of two different semi-synthetic
hydrogenases in vivo. [FeFe] hydrogenases are metalloenzymes that catalyze the
interconversion of molecular hydrogen and protons. The reaction is catalyzed by
the H-cluster, consisting of a canonical iron-sulfur cluster and an
organometallic [2Fe] subsite. It was recently shown that the enzyme can be
reconstituted with synthetic cofactors mimicking the composition of the [2Fe]
subsite, resulting in semi-synthetic hydrogenases. Herein, we employ EPR
spectroscopy to monitor the formation of two such semi-synthetic enzymes in whole
cells. The study provides the first spectroscopic characterization of semi
synthetic hydrogenases in vivo, and the observation of two different oxidized
states of the H-cluster under intracellular conditions. Moreover, these findings
underscore how synthetic chemistry can be a powerful tool for manipulation and
examination of the hydrogenase enzyme under in vivo conditions.
PMID- 29334426
TI - Current Resources for Evidence-Based Practice, January/February 2018.
PMID- 29334425
TI - Updates From the Literature, January/February 2018.
PMID- 29334427
TI - Management of Labor: Are the New Guidelines Justified?
PMID- 29334428
TI - Development of Potent Inhibitors of the Mycobacterium tuberculosis Virulence
Factor Zmp1 and Evaluation of Their Effect on Mycobacterial Survival inside
Macrophages.
AB - The enzyme Zmp1 is a zinc-containing peptidase that plays a critical role in the
pathogenicity of Mycobacterium tuberculosis. Herein we describe the
identification of a small set of Zmp1 inhibitors based on a novel 8
hydroxyquinoline-2-hydroxamate scaffold. Among the synthesized compounds, N
(benzyloxy)-8-hydroxyquinoline-2-carboxamide (1 c) was found to be the most
potent Zmp1 inhibitor known to date, and its binding mode was analyzed both by
kinetics studies and molecular modeling, identifying critical interactions of 1 c
with the zinc ion and residues in the active site. The effect of 1 c on
intracellular Mycobacterium survival was assayed in J774 murine macrophages
infected with M. tuberculosis H37Rv or M. bovis BCG and human monocyte-derived
macrophages infected with M. tuberculosis H37Rv. Cytotoxicity and genotoxicity
were also assessed. Overall, inhibitor 1 c displays interesting in vitro
antitubercular properties worthy of further investigation.
PMID- 29334429
TI - Superhydrophobic/Superhydrophilic Janus Fabrics Reducing Blood Loss.
AB - Hemostatic fabrics are most commonly used in baseline emergency treatment;
however, the unnecessary blood loss due to the excessive blood absorption by
traditional superhydrophilic fabrics is overlooked. Herein, for the first time,
superhydrophobic/superhydrophilic Janus fabrics (superhydrophobic on one side and
superhydrophilic on the other) are proposed: the superhydrophilic part absorbs
water in the blood to expedite the clotting while the superhydrophobic part
prevents blood from further permeating. Compared with the common counterparts,
effective bleeding control with reducing blood loss more than 50% can be achieved
while the breathability largely remain by using Janus fabrics. The proposed
prototypes can even prolong the survival time in the rat model with serious
bleeding. This strategy for reducing blood loss via simply tuning wettability is
promising for the practical applications.
PMID- 29334430
TI - Preclinical therapeutic efficacy of the ciprofloxacin-eluting sinus stent for
Pseudomonas aeruginosa sinusitis.
AB - BACKGROUND: The ciprofloxacin-coated sinus stent (CSS) has unique therapeutic
potential to deliver antibiotics to the sinuses. The objective of this study is
to evaluate the efficacy of the CSS stent in eliminating Pseudomonas aeruginosa
infection in a rabbit model of sinusitis. METHODS: A ciprofloxacin-eluting sinus
stent was created by coating ciprofloxacin/Eudragit RS100 on biodegradable poly
D/L-lactic acid (2 mg). After analyzing in-vitro inhibition of P aeruginosa (PAO
1 strain) biofilm formation, a total of 8 stents (4 shams, 4 CSSs) were placed
unilaterally in rabbit maxillary sinuses via dorsal sinusotomy after inducing
infection for 1 week with PAO-1. Animals were assessed 2 weeks after stent
insertion with nasal endoscopy, sinus culture, computed tomography (CT) scan,
histopathology, and scanning electron microscopy (SEM). RESULTS: PAO-1 biofilm
formation was significantly reduced in vitro with exposure to the CSS (p <
0.0001). Insertion of the stent in PAO-1-infected rabbits for 2 weeks resulted in
significant improvement in sinusitis according to endoscopy scoring (p < 0.0001)
and CT scoring (p < 0.002). Histology and SEM revealed marked improvement in the
structure of the mucosa and submucosa with no detection of biofilm structures in
the CSS cohort. CONCLUSION: Although this study had a small sample size, we
identified robust therapeutic efficacy of the CSS by reducing bacterial load and
biofilm formation of P aeruginosa in a preclinical model of sinusitis after
placement for 2 weeks.
PMID- 29334431
TI - Activation state of circulating eosinophils in nasal polyposis.
AB - BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common disease
with an uncertain pathophysiology. It is characterized by polyps rich in
eosinophils, with an activation status already investigated at the tissue level.
In a group of CRSwNP patients, we assessed the activation status of circulating
eosinophils in the blood before migration into tissues. METHODS: Thirteen
patients with CRSwNP and 16 healthy volunteers were enrolled. Several biologic
parameters were studied: blood count of eosinophils; plasma eosinophil cationic
protein; oxidative metabolism by chemiluminescence at baseline or when activated
by phorbol 12-myristate 13-acetate or platelet-activating factor, with or without
interleukin-5 (IL-5); percent of granulosar cells; and mean fluorescence
intensity (MFI) by flow cytometry. RESULTS: The mean number of eosinophils was
significantly higher in patients with CRSwNP, whose eosinophils showed increased
oxidative metabolism in the basal or activated state significantly decreasing in
the presence of IL-5. There was also a higher percentage of CD49d+ , CD25+ , and
CCR3+ cells in patients, and a nonsignificant decrease in descending order in MFI
between the control group, patients with normal eosinophil levels, patients with
hypereosinophilia, and patients with aspirin-exacerbated respiratory disease.
CONCLUSION: This study demonstrates a priming state of circulating eosinophils in
CRSwNP patients when compared with healthy controls, as evidenced by the extent
of oxidative metabolism, with increased sensitivity to IL-5 and by the observed
variations of percent and MFI of CD49d, CCR3, and CD25. This priming is thus
found at the peripheral level and occurs before the migration of eosinophils to
polyps, reflecting the systemic and not just local nature of abnormalities in
CRSwNP.
PMID- 29334432
TI - Antibiotic use patterns in endoscopic sinus surgery: a survey of the American
Rhinologic Society membership.
AB - BACKGROUND: There is a paucity of data supporting antibiotic use in endoscopic
sinus surgery (ESS). The objective of this study is to determine perioperative
antibiotic use patterns and factors which influence use in ESS. METHODS: An
online-based survey was distributed to members of the American Rhinologic Society
(ARS). Outcomes included timing of perioperative antibiotic use, practice
environment, years of experience, and patient factors that influenced antibiotic
use. RESULTS: There were 204 responses (response rate 18.3%); 36.8% of
respondents were in academic positions, 32.8% were in private practice, and 30.4%
were in academic-affiliated private practice; 20.6% routinely gave preoperative
antibiotics, most commonly to reduce bacterial burden (59.5%) and mucosal
inflammation (59.5%); 54.4% routinely gave intraoperative antibiotics, most
commonly to reduce the risk of postoperative infection (63.1%); 62.3% routinely
gave postoperative antibiotics, citing the need to reduce the risk of
postoperative infection (75.6%). Diagnosis influenced postoperative antibiotic
use in 63.0%. Preoperative antibiotics were more likely to be prescribed by
respondents with more than 5 years of experience (odds ratio [OR] 2.97; 95%
confidence interval [CI], 1.04 to 8.54; p = 0.043). Compared to private
practitioners, academicians were more likely to give intraoperative antibiotics
(OR 2.68; 95% CI, 1.39 to 5.17; p = 0.003), but not preoperative or postoperative
antibiotics. Use of nonabsorbable packing was significantly associated with use
of postoperative antibiotics (OR 2.01; 95% CI, 1.07 to 3.77; p = 0.031).
CONCLUSION: This study demonstrates the significant variation in perioperative
antibiotic use among otolaryngologists. These results provide support for the
establishment of evidence-based practice guidelines for perioperative antibiotic
use in ESS.
PMID- 29334433
TI - Happy Birthday Karel!
PMID- 29334434
TI - The Case for Stabilized Stannous Fluoride Dentifrice: An Advanced Formulation
Designed for Patient Preference.
AB - Oral diseases, particularly caries and gingivitis, continue to be widespread.
Incorporating a stabilized stannous fluoride dentifrice into patients' daily oral
hygiene routine is a convenient, cost effective approach to improve and protect
their oral health and the appearance of their smile. Unlike other common
fluorides that only provide anti-caries benefits (e.g., sodium fluoride and
sodium monofluorophosphate), stabilized stannous fluoride formulations have
demonstrated broader and significantly greater protection, also reducing plaque,
gingivitis, erosion, sensitivity, and halitosis. To deliver the full range of
benefits and simultaneously deliver whitening and tartar control benefits,
stannous fluoride requires careful formulation. Procter & Gamble is the only
dentifrice manufacturer with decades of patented innovations to overcome these
formulation challenges, resulting in a large portfolio of stannous fluoride
containing dentifrice products marketed under the Crest(r) Pro-HealthTM name that
are available today. The most recent innovation is a "smooth texture" variant of
Crest Pro-Health, containing stabilized stannous fluoride with zinc citrate as
the anti-calculus agent. This product was developed to deliver a patient
preferred brushing experience with the full range of benefits offered by Crest
Pro-Health. This article discusses two common misconceptions about dentifrice,
describes the history of key Crest stannous fluoride innovations, and outlines
the research in this issue demonstrating health and cosmetic benefits of the new
Crest Pro-Health smooth texture variant.
PMID- 29334435
TI - Comparative Antiplaque Effect of Two Antimicrobial Dentifrices: Laboratory and
Clinical Evaluations.
AB - OBJECTIVES: To compare the effect of a stannous fluoride dentifrice versus a
triclosan-containing dentifrice on the reduction of plaque using in vitro and
clinical models. METHODS: Both investigations evaluated a novel 0.454% stabilized
stannous fluoride dentifrice (Crest(r) Pro-HealthTM smooth formula) versus a
sodium fluoride/triclosan positive control dentifrice (Colgate(r) Total(r)). The
in vitro evaluation utilized the Plaque Glycolysis and Regrowth Model (PGRM),
wherein the metabolic effects (acid production/glycolysis inhibition) of the
dentifrices were assessed on plaque biofilms grown on glass rods after three days
growth and a single dentifrice treatment. Treatments were evaluated via analysis
of variance, Student's t-test. The clinical trial was a four-week, single-center,
randomized and controlled, double-blind, parallel group study, where 120 adults
were randomized to one of the two dentifrices for use at home according to
manufacturer's instructions. Plaque was evaluated at baseline and Week 4 with the
Rustogi Modified Navy Plaque Index (RMNPI). Statistical analyses were via
analysis of covariance. RESULTS: In vitro PGRM: The stannous fluoride dentifrice
provided 43.3% glycolysis inhibition compared to 27.5% for the triclosan control,
and the pH decrease associated with acid production was significantly less for
stannous fluoride (0.87) versus triclosan (1.11); p < 0.05. Clinical trial: One
hundred eighteen (118) subjects completed the study with fully evaluable data.
Both dentifrice groups demonstrated statistically significant (p < 0.0001)
reductions in plaque at Week 4 compared with baseline, with the stannous fluoride
dentifrice producing a significantly lower adjusted mean Week 4 plaque score (p <
0.0001) versus the triclosan positive control for whole mouth plaque (23.1%
lower) and interproximal plaque (43.5% lower). Both dentifrices were well
tolerated. CONCLUSIONS: The stabilized stannous fluoride dentifrice provided
statistically significant reductions in plaque glycolysis in vitro and plaque
growth in vivo compared to the triclosan dentifrice. Results for both studies
were consistent.
PMID- 29334436
TI - Assessment of the Effects of a Novel Stabilized Stannous Fluoride Dentifrice on
Gingivitis in a Two-Month Positive-Controlled Clinical Study.
AB - OBJECTIVES: The aim of this study was to compare the antibleeding/antigingivitis
effectiveness of a newly formulated 0.454% stabilized stannous fluoride
dentifrice and a marketed positive control triclosan-containing dentifrice in
adults with mild-to-moderate gingivitis. METHODS: This single-center, two-month,
randomized and controlled, double-blind, parallel group clinical trial involved
adults with preexisting mild-to-moderate gingivitis. Baseline bleeding and
gingivitis levels were assessed with the Gingival Bleeding Index (GBI) and Lobene
Modified Gingival Index (MGI). Subjects were randomly assigned to either a new
smooth formula 0.454% stabilized stannous fluoride test dentifrice (Crest(r) Pro
HealthTM) or a commercially available positive control 0.30% triclosan dentifrice
(Colgate(r) Total(r)). Subjects brushed with their assigned dentifrice at home
according to the manufacturer's instructions. At Month 2, subjects were re
evaluated for bleeding and gingivitis as at Baseline, with MGI and GBI
evaluations. RESULTS: Of the 200 subjects randomized to treatment, 197 completed
the study and had fully evaluable data. At Month 2, both the stannous fluoride
and triclosan control dentifrices produced statistically significant reductions
(p < 0.0001) in the mean number of bleeding sites, MGI, and GBI compared to
Baseline. Use of this 0.454% stannous fluoride dentifrice resulted in 22% fewer
bleeding sites versus the positive control triclosan dentifrice (p < 0.0001).
Similarly, after two months of brushing, the stannous fluoride dentifrice group
showed statistically significant lower mean MGI and GBI scores than subjects
using the triclosan positive control dentifrice (p < 0.0001). Both dentifrices
were well-tolerated. CONCLUSIONS: Subjects brushing with a newly formulated
stannous fluoride dentifrice had statistically significantly fewer bleeding sites
and less gingivitis than those using a positive control triclosan dentifrice
after two months.
PMID- 29334437
TI - A Randomized Clinical Trial to Measure the Erosion Protection Benefits of a Novel
Stabilized Stannous Fluoride Dentifrice versus a Control Dentifrice.
AB - OBJECTIVES: The aim of this investigation was to assess the erosion protection
ability of a novel stabilized stannous fluoride (SnF2) dentifrice and a control
sodium fluoride dentifrice (NaF) using a well-credentialed human in situ model.
METHODS: A novel smooth texture 0.454% stabilized SnF2 dentifrice (Crest(r) Pro
HealthTM smooth formula) and a 0.23% NaF marketed control dentifrice with 5%
potassium nitrate (Sensodyne(r) Pronamel(r)) were compared in a 10-day, single
center, randomized, controlled, double-blind, two-treatment, three-period
crossover in situ clinical trial. Subjects wore a mandibular buccal appliance
fitted with eight enamel specimens for approximately six hours over the course of
each study day. Twice daily, subjects brushed the lingual surfaces of their teeth
for 30 seconds while wearing the appliance, then swished with their assigned
treatment toothpaste slurry for 90 seconds under the supervision of clinic staff.
Erosive acid challenges with a citric acid-containing beverage (commercial orange
juice) were done four times each day. RESULTS: The SnF2 dentifrice provided 26.9%
greater erosion protection relative to the NaF dentifrice at Day 10 (p < 0.03).
Adjusted means of enamel surface loss at Day 10 were 9.117 um for the SnF2
dentifrice and 12.471 um for the NaF marketed control. CONCLUSIONS: These results
demonstrate the stabilized SnF2 dentifrice offered greater protection over the
NaF dentifrice against the initiation and progression of dental erosion.
PMID- 29334438
TI - In Vitro and In Vivo Evaluations of the Anticalculus Effect of a Novel Stabilized
Stannous Fluoride Dentifrice.
AB - OBJECTIVES: To evaluate the effect of a novel stannous fluoride dentifrice with
zinc citrate on calculus inhibition using both in vitro and clinical models.
METHODS: Each investigation tested a novel stabilized 0.454% stannous fluoride
dentifrice with zinc citrate as an anticalculus agent (Crest(r) Pro-HealthTM
smooth formula) compared to a negative control fluoride dentifrice. The in vitro
study used the modified Plaque Growth and Mineralization Model (mPGM). Plaque
biofilms were prepared and mineralized by alternate immersion of glass rods in
human saliva and artificial mineralization solution. Treatments of 25% w/w
dentifrice/water slurries were carried out for 60 seconds daily for 6 days,
between saliva and mineralization solution immersions. Plaque calcium levels were
determined by digestion and inductively coupled plasma optical emission
spectroscopy. Student's t-test (p < 0.05) was used for statistical analysis. The
clinical study was a parallel group, double-blind, randomized, and controlled
trial. Following a dental prophylaxis, subjects entered a two-month run-in phase.
At the end, they received a Volpe-Manhold Index (V-MI) calculus examination.
Eighty (80) qualified subjects who had formed at least 9 mm of calculus on the
linguals of the mandibular anterior teeth were re-prophied and randomly assigned
to either the stannous fluoride dentifrice or the negative control. Subjects
brushed twice daily, unsupervised, during the three-month test period, returning
at Weeks 6 and 12 for safety and V-MI examinations. Statistical analyses were via
ANCOVA. RESULTS: In vitro mPGM: The stabilized stannous fluoride dentifrice
showed 20% less in vitro tartar formation, measured as calcium accumulation
normalized by biofilm mass, versus the negative control (106.95 versus 133.04 ug
Ca/mg biofilm, respectively, p < 0.05). Clinical Trial: Seventy-eight (78)
subjects completed with fully evaluable data. The stannous fluoride dentifrice
group had 15.1% less adjusted mean calculus at Week 6 compared to the negative
control group (p = 0.05) and 21.7% less calculus at Week 12 (p < 0.01). Both
dentifrices were well-tolerated. CONCLUSIONS: The stannous fluoride dentifrice
produced significant anticalculus benefits in vitro and in a clinical trial
compared to a negative control.
PMID- 29334439
TI - Pharmacogenetics - The Year in Review.
PMID- 29334440
TI - Multifactorial Splenomegaly.
AB - Splenomegaly is an unusual finding among North Americans, but is commonly seen in
many parts of the world. Increasingly, it can be encountered locally among recent
immigrant and refugee populations. A broad differential diagnosis is required. We
report the case of a 33-year-old refugee with multiple potential causes for
splenomegaly. Empiric treatment of one of the infectious contributors to his
splenomegaly resulted in a significant improvement of his quality of life,
illustrating the importance of a thorough evaluation of potential causes of
splenomegaly, especially in refugee and immigrant populations.
PMID- 29334441
TI - Statin Pharmacogenetics: Moving from Toxicity to Efficacy.
PMID- 29334443
TI - The Sanford School of Medicine's Healthcare Quality Improvement Program:
Connecting Education with Quality Improvement.
PMID- 29334442
TI - A Rare Initial Presentation of Primary Diffuse Leptomeningeal PNET in a 10-Year
Old-Male.
AB - Primary leptomeningeal primitive neuroectodermal tumors (PNETs) are extremely
rare childhood central nervous system malignancies harboring a very poor
prognosis. There is no consensus treatment for these tumors to date. We report a
case of a 10-year-old male who presented with mental status change,
hydrocephalus, intracranial and spinal diffuse leptomeningeal enhancement without
a primary mass upon cranial imaging and a negative initial biopsy until five
months into his presentation. He responded significantly well to initial
chemotherapy and radiotherapy.
PMID- 29334444
TI - Pregnancy and Parenthood During Medical School.
AB - PURPOSE: The stress of pregnancy and parenthood during the intense educational
experience of medical school could increase the risk of student burnout. Because
9.2 percent of U.S. medical students are parents by graduation, it would seem
prudent to include this topic in wellness programs and policies. The purpose of
this study was to determine the effects of pregnancy and parenthood on medical
students. METHOD: This was a cross-sectional, internet survey distributed to all
four classes of medical students at the University of South Dakota Sanford School
of Medicine during the 2016-2017 academic year. The survey determined self
reported pregnancy and parenthood information, knowledge of a medical school
pregnancy policy, and policy recommendations. RESULTS: More than 85 percent of
the 194 respondents recommended that the following elements be included in an
institutional policy: process for arranging parental leave, how leave time might
affect graduation, how missed requirements could be made up, and how to request
special accommodation or leave. Twenty-nine of the respondents (15 percent) were
parents or currently pregnant. Eight pregnancies during medical school were
associated with complications, including three miscarriages. Of the 18 students
who reported maternity or paternity leave, 13 (72 percent) and 10 (56 percent)
would have extended their leave time if it did not delay graduation or only
reduced their number of elective rotations, respectively. No student would choose
to extend leave if it would delay graduation. CONCLUSIONS: This survey is the
first of its kind investigating pregnancy and parenthood in medical students
attending a U.S. medical school. Students want schools to provide clear, well
defined guidelines, scheduling flexibility and administrators who are
approachable and understanding of their individual circumstances.
PMID- 29334445
TI - The Father of the Problem Oriented Medical Record.
PMID- 29334446
TI - Pediatric Community Acquired Pneumonia.
AB - Pediatric community acquired pneumonia (CAP) is frequently encountered by medical
providers and is one of the most common reasons for hospital admission. CAP is
known to cause significant morbidity and mortality, causing greater than 2
million deaths annually worldwide in children younger than five years old. The
Infectious Disease Society of America (IDSA) released guidelines in 2011 with
recommendations regarding appropriate diagnosis and management of community
acquired pneumonia for children greater than 3 months age, with the goal of
assisting providers in clinical decision making. The guidelines do not recommend
routine diagnostic work up for previously healthy, appropriately immunized
patients presenting with mild CAP and are otherwise candidates for outpatient
treatment. Diagnostic work up indicated for patients presenting with moderate to
severe disease include CBC with differential, blood culture, acute phase
reactants and chest radiography. Providers may also consider testing for
influenza, mycoplasma pneumoniae, and other viral respiratory pathogens depending
on the patient's presentation. Antibiotics are not routinely recommended, as the
majority of cases are caused by viral pathogens. Narrow spectrum antibiotics are
indicated for empiric treatment of bacterial CAP in fully immunized pediatric
patients who are not penicillin allergic. Despite these new recommendations,
there continues to be delay in changing the methods of practice in some hospitals
and clinics. It is important that providers are familiar with the most current
guidelines to minimize unnecessary laboratory testing and imaging in the
outpatient setting for mild cases, and to use evidence based recommendations for
laboratory work up, imaging, and treatment in the inpatient setting.
PMID- 29334447
TI - The Heart of the Matter: Antidiabetic Medication Effects on Cardiovascular
Outcomes.
PMID- 29334448
TI - Quality Focus: Expanding Quality Improvement to Achieve Positive Health Outcomes.
PMID- 29334454
TI - Aurophilic Interactions in [(L)AuCl]...[(L')AuCl] Dimers: Calibration by
Experiment and Theory.
AB - Attractive metallophilic (aurophilic, argentophilic, cuprophilic, etc.)
interactions play an important role in arrangement and stabilization of
oligonuclear metal ion complexes. We report a combined experimental and
theoretical assessment of aurophilic interactions in closed-shell gold(I) dimers.
The experimental binding energies were obtained for charged
[(LH)AuCl]+...[(L')AuCl] dimers (L is either a phosphine or an N-heterocyclic
carbene ligand) in the gas phase. These energies served for benchmarking of
correlated quantum chemical calculations (CCSD(T)-calibrated SCS-MP2/CBS method)
that were then applied to neutral [(L)AuCl]...[(L')AuCl] dimers. The overall
attractive interactions between monomeric units are in the order of 100-165 kJ
mol-1 in the charged dimers and of 70-105 kJ mol-1 in the corresponding neutral
dimers. In the neutral dimers, pure aurophilic interactions account for 25-30 kJ
mol-1, the dipole-dipole interactions for 30-45 kJ mol-1, and the L...L' "inter
ligand" dispersion interactions for 5-25 kJ mol-1. Energy of the aurophilic
interactions is thus comparable or even larger than that of strong hydrogen
bonds.
PMID- 29334455
TI - Modulating the Molybdenum Coordination Sphere of Escherichia coli Trimethylamine
N-Oxide Reductase.
AB - The well-studied enterobacterium Escherichia coli present in the human gut can
reduce trimethylamine N-oxide (TMAO) to trimethylamine during anaerobic
respiration. The TMAO reductase TorA is a monomeric, bis-molybdopterin guanine
dinucleotide (bis-MGD) cofactor-containing enzyme that belongs to the dimethyl
sulfoxide reductase family of molybdoenzymes. We report on a system for the in
vitro reconstitution of TorA with molybdenum cofactors (Moco) from different
sources. Higher TMAO reductase activities for TorA were obtained when using Moco
sources containing a sulfido ligand at the molybdenum atom. For the first time,
we were able to isolate functional bis-MGD from Rhodobacter capsulatus formate
dehydrogenase (FDH), which remained intact in its isolated state and after
insertion into apo-TorA yielded a highly active enzyme. Combined
characterizations of the reconstituted TorA enzymes by electron paramagnetic
resonance spectroscopy and direct electrochemistry emphasize that TorA activity
can be modified by changes in the Mo coordination sphere. The combination of
these results together with studies of amino acid exchanges at the active site
led us to propose a novel model for binding of the substrate to the molybdenum
atom of TorA.
PMID- 29334456
TI - Building Ion-Conduction Highways in Polymeric Electrolytes by Manipulating
Protein Configuration.
AB - Solid polymer electrolytes play a critical role in the development of safe,
flexible, and all-solid-state energy storage devices. However, the low ion
conductivity has been the primary challenge impeding them from practical
applications. Here, we propose a new biotechnology to fabricate novel protein
ceramic hybrid nanofillers for simultaneously boosting the ionic conductivity,
mechanical properties, and even adhesion properties of solid polymer
electrolytes. This hybrid nanofiller is fabricated by coating ion-conductive soy
proteins onto TiO2 nanoparticles via a controlled denaturation process in
appropriate solvents and conditions. It is found that the chain configuration and
protein/TiO2 interactions in the hybrid nanofiller play critical roles in
improving not only the mechanical properties but also the ion conductivity,
electrochemical stability, and adhesion properties. Particularly, the ion
conductivity is improved by one magnitude from 5 * 10-6 to 6 * 10-5 S/cm at room
temperature. To understand the possible mechanisms, we perform molecular
simulation to study the chain configuration and protein/TiO2 interactions.
Simulation results indicate that the denaturation environment and procedures can
significantly change the protein configuration and the protein/TiO2 interactions,
both of which are found to be critical for the ion conductivity and mechanical
properties of the resultant solid composite electrolytes. This study indicates
that biotechnology of manipulating protein configuration can bring novel and
promising strategies to build unique ion channels for fast ion conduction in
solid polymer electrolytes.
PMID- 29334457
TI - New Mechanism for Ferroelectricity in the Perovskite Ca2-xMnxTi2O6 Synthesized by
Spark Plasma Sintering.
AB - Perovskite oxides hosting ferroelectricity are particularly important materials
for modern technologies. The ferroelectric transition in the well-known oxides
BaTiO3 and PbTiO3 is realized by softening of a vibration mode in the cubic
perovskite structure. For most perovskite oxides, octahedral-site tilting systems
are developed to accommodate the bonding mismatch due to a geometric tolerance
factor t = (A-O)/[?2(B-O)] < 1. In the absence of cations having lone-pair
electrons, e.g., Bi3+ and Pb2+, all simple and complex A-site and B-site ordered
perovskite oxides with a t < 1 show a variety of tilting systems, and none of
them become ferroelectric. The ferroelectric CaMnTi2O6 oxide is, up to now, the
only one that breaks this rule. It exhibits a columnar A-site ordering with a
pronounced octahedral-site tilting and yet becomes ferroelectric at Tc ~ 650 K.
Most importantly, the ferroelectricity at T < Tc is caused by an order-disorder
transition instead of a displacive transition; this character may be useful to
overcome the critical thickness problem experienced in all proper ferroelectrics.
Application of this new ferroelectric material can greatly simplify the structure
of microelectronic devices. However, CaMnTi2O6 is a high-pressure phase obtained
at 7 GPa and 1200 degrees C, which limits its application. Here we report a new
method to synthesize a gram-level sample of ferroelectric Ca2-xMnxTi2O6, having
the same crystal structure as CaMnTi2O6 and a similarly high Curie temperature.
The new finding paves the way for the mass production of this important
ferroelectric oxide. We have used neutron powder diffraction to identify the
origin of the peculiar ferroelectric transition in this double perovskite and to
reveal the interplay between magnetic ordering and the ferroelectric displacement
at low temperatures.
PMID- 29334458
TI - Direct Electrochemical Vibrio DNA Sensing Adopting Highly Stable Graphene-Flavin
Mononucleotide Aqueous Dispersion Modified Interface.
AB - A biofunctionalized graphene nanohybrid was prepared by simultaneously sonicating
graphene and riboflavin 5'-monophosphate sodium salt (FMNS). FMNS, as a
biodispersant, showed an efficient stabilization for obtaining highly dispersed
graphene nanosheets in an aqueous solution. Due to the superior dispersion of
graphene and the excellent electrochemical redox activity of FMNS, a direct
electrochemical DNA sensor was fabricated by adopting the inherent
electrochemical redox activity of graphene-FMNS (Gr-FMNS). The comparison between
using traditional electrochemical indicator ([Fe(CN)6]3-/4-) and using the self
signal of Gr-FMNS was fully conducted to study the DNA-sensing performance. The
results indicate that the proposed DNA-sensing platform displays fine
selectivity, high sensitivity, good stability, and reproducibility using either
[Fe(CN)6]3-/4- probe or the self-signal of Gr-FMNS. The two methods display the
same level of detection limit: 7.4 * 10-17 M (using [Fe(CN)6]3-/4-) and 8.3 * 10
17 M (using self-signal), respectively, and the latter exhibits higher
sensitivity. Furthermore, the sensing platform also can be applied for the DNA
determination in real samples.
PMID- 29334460
TI - Multiple Stimuli Responses of Stereo-Isomers of AIE-Active Ethynylene-Bridged and
Pyridyl-Modified Tetraphenylethene.
AB - Luminescent molecules with aggregation-induced emission (AIE) property or AIE
active luminogens (AIE-gens) are typical stimuli-responsive materials. Many AIE
gens have shown luminescent responses to mechano-, thermo-, electro-, vapo-,
and/or solvato-stimulus, but the detailed structure-property relationship has
been addressed for only a few of them. Here, we report a tetraphenylethene (TPE)
derivative with pyridyl modifiers and ethynylene bridges. The (Z)- and (E)
isomers are clearly purified, and both of them are AIE-active and demonstrate
multiple luminescent responses to external stimuli. Distinct from other reported
TPE derivatives, the two isomers show negative solvatochromism due to the large
dipole in the ground electronic state. By correlating with the single crystal
structures, the subtle differences in quantum efficiency and emission peak
wavelength of the solids of the (Z)- and (E)-isomers are rationally explained.
Moreover, the ground powder of the (E)-isomer can recover its emission color from
green to blue in the air at room temperature but the (Z)-isomer cannot. This
difference is interpreted by a mechanism of water-triggered conformational
variation, which depends on the hydrogen bond formation between pyridyl moieties
and water molecules in the air. In addition to the reversible emission color
changes by cyclic grinding-fuming treatments, both of the isomers exhibit a
reversible luminescent response to acid-base treatments by switching the emission
color between green (basic) and yellow (acid), owing to the incorporation of
pyridyl units into the molecule. The unprecedented multiple stimuli-responsive
behaviors and clear mechanism explanations allow this kind of AIE-gens to be
promising smart materials.
PMID- 29334459
TI - Development of CHARMM-Compatible Force-Field Parameters for Cobalamin and Related
Cofactors from Quantum Mechanical Calculations.
AB - Corrinoid cofactors such as cobalamin are used by many enzymes and are essential
for most living organisms. Therefore, there is broad interest in investigating
cobalamin-protein interactions with molecular dynamics simulations. Previously
developed parameters for cobalamins are based mainly on crystal structure data.
Here, we report CHARMM-compatible force field parameters for several corrinoids
developed from quantum mechanical calculations. We provide parameters for
corrinoids in three oxidation states, Co3+, Co2+, and Co1+, and with various
axial ligands. Lennard-Jones parameters for the cobalt center in the Co(II) and
Co(I) states were optimized using a helium atom probe, and partial atomic charges
were obtained with a combination of natural population analysis (NPA) and
restrained electrostatic potential (RESP) fitting approaches. The Force Field
Toolkit was used to optimize all bonded terms. The resulting parameters,
determined solely from calculations of cobalamin alone or in water, were then
validated by assessing their agreement with density functional theory geometries
and by analyzing molecular dynamics simulation trajectories of several corrinoid
proteins for which X-ray crystal structures are available. In each case, we
obtained excellent agreement with the reference data. In comparison to previous
CHARMM-compatible parameters for cobalamin, we observe a better agreement for the
fold angle and lower RMSD in the cobalamin binding site. The approach described
here is readily adaptable for developing CHARMM-compatible force-field parameters
for other corrinoids or large biomolecules.
PMID- 29334461
TI - Enhanced Proton Loss from Neutral Free Radicals: Toward Carbon-Centered
Superacids.
AB - Radical centers close to protons are known to enhance their dissociation.
Investigation of the generality of this radical enhanced deprotonation (RED
shift) phenomenon, and the kinds of structures in which it operates, are
reported. The pKas for sulfinic, sulfonic, pentan-2,4-dione, and Meldrum's acid
species, with adjacent radicals centered on C-, N-, and O atoms, were computed by
a DFT method from free energies of deprotonation. All series showed significant
RED-shifts that increased with the electronegativity of the radical center. The
hugely negative pKa obtained for a Meldrum's acid with an alkoxyl radical
substituent showed it to belong to the superacid class. The ethyne unit was found
to be uniquely effective at enhancing acidity and conducting RED-shifts through
chains up to and beyond 20 atoms. These connector units enable a radical center
to alter the pKa of a spatially remote acidic group. RED-shifted species were
characterized by conjugate radical anions displaying site exchange of spin with
electronic charge.
PMID- 29334463
TI - Torquoselective Mechanochemical Activation of the Staudinger Reaction To Form
beta-Lactams.
AB - The Staudinger reaction yielding beta-lactam rings via [2 + 2] cycloaddition is a
torquoselective reaction where the stereochemistry of the product can be steered
by suitable substituents. Although the mechanochemical ring-opening of beta
lactams has been investigated recently, the force-assisted synthesis of this
important functional four-ring motif remains unexplored. As it will be
computationally demonstrated, mechanochemical activation greatly reduces the
barrier of the rate-limiting ring-closure step while, at the same time, preserves
its torquoselectivity. This finding strongly suggests that strained four-membered
rings can be readily incorporated in chain molecules using sonication techniques
that greatly enhance reactivity while conserving selectivity.
PMID- 29334462
TI - Pot-Economy Autooxidative Condensation of 2-Aryl-2-lithio-1,3-dithianes.
AB - The autoxidative condensation of 2-aryl-2-lithio-1,3-dithianes is here reported.
Treatment of 2-aryl-1,3-dithianes with n-BuLi in the absence of any electrophile
leads to condensation of three molecules of 1,3-dithianes and formation of highly
functionalized alpha-thioether ketones orthothioesters in 51-89% yields upon air
exposure. The method was further expanded to benzaldehyde dithioacetals,
affording corresponding orthothioesters and alpha-thioether ketones in 48-97%
yields. The experimental results combined with density functional theory studies
support a mechanism triggered by the autoxidation of 2-aryl-2-lithio-1,3
dithianes to yield a highly reactive thioester that undergoes condensation with
two other molecules of 2-aryl-2-lithio-1,3-dithiane.
PMID- 29334464
TI - Asymmetric Synthesis of Secondary and Tertiary Propargylic Alcohols by Umpolung
of Acetylenic Sulfones and ortho-Sulfinyl Carbanions.
AB - The generation of diastereomerically enriched secondary benzyl propargyl alcohols
by the asymmetric addition of ortho-sulfinylbenzyl carbanions to
sulfonylacetylene derivatives via formation of a Csp-Csp3 bond is described. This
reaction proceeds through an unusual alpha-attack (anti-Michael addition) of the
ortho-sulfinylbenzyl carbanions, followed by elimination of the arylsulfonyl
moiety. The scope of this alkynylation reaction is also discussed. Moreover, the
development of a new approach for the synthesis of optically active tertiary
benzylpropargyl alcohols is described, discussing the possible stereocourse of
the reaction so as the influence of the ether 18-crown-6 and steric importance of
acetylenic substituent.
PMID- 29334466
TI - alpha-N-Heteroarylation and alpha-Azidation of Ketones via Enolonium Species.
AB - Enolonium species, resulting from the umpolung of ketone enolates by Koser's
hypervalent iodine reagents activated by boron trifluoride, react with a variety
of nitrogen heterocycles to form alpha-aminated ketones. The reactions are mild
and complete in 4-5 h. Additionally, alpha-azidation of the enolonium species
takes place using trimethylsilyl azide as a convenient source of azide
nucleophile.
PMID- 29334465
TI - Design of a "Mini" Nucleic Acid Probe for Cooperative Binding of an RNA-Repeated
Transcript Associated with Myotonic Dystrophy Type 1.
AB - Toxic RNAs containing expanded trinucleotide repeats are the cause of many
neuromuscular disorders, one being myotonic dystrophy type 1 (DM1). DM1 is
triggered by CTG-repeat expansion in the 3'-untranslated region of the DMPK gene,
resulting in a toxic gain of RNA function through sequestration of MBNL1 protein,
among others. Herein, we report the development of a relatively short miniPEG
gamma peptide nucleic acid probe, two triplet repeats in length, containing
terminal pyrene moieties, that is capable of binding rCUG repeats in a sequence
specific and selective manner. The newly designed probe can discriminate the
pathogenic rCUGexp from the wild-type transcript and disrupt the rCUGexp-MBNL1
complex. The work provides a proof of concept for the development of relatively
short nucleic acid probes for targeting RNA-repeat expansions associated with DM1
and other related neuromuscular disorders.
PMID- 29334469
TI - Erratum.
PMID- 29334467
TI - Robot-assisted upper extremity rehabilitation for cervical spinal cord injuries:
a systematic scoping review.
AB - : Abstact Purpose: To provide an overview of the feasibility and outcomes of
robotic-assisted upper extremity training for individuals with cervical spinal
cord injury (SCI), and to identify gaps in current research and articulate future
research directions. MATERIALS AND METHODS: A systematic search was conducted
using Medline, Embase, PsycINFO, CCTR, CDSR, CINAHL and PubMed on June 7, 2017.
Search terms included 3 themes: (1) robotics; (2) SCI; (3) upper extremity.
Studies using robots for upper extremity rehabilitation among individuals with
cervical SCI were included. Identified articles were independently reviewed by
two researchers and compared to pre-specified criteria. Disagreements regarding
article inclusion were resolved through discussion. The modified Downs and Black
checklist was used to assess article quality. Participant characteristics, study
and intervention details, training outcomes, robot features, study limitations
and recommendations for future studies were abstracted from included articles.
RESULTS: Twelve articles (one randomized clinical trial, six case series, five
case studies) met the inclusion criteria. Five robots were exoskeletons and three
were end-effectors. Sample sizes ranged from 1 to 17 subjects. Articles had
variable quality, with quality scores ranging from 8 to 20. Studies had a low
internal validity primarily from lack of blinding or a control group. Individuals
with mild-moderate impairments showed the greatest improvements on body
structure/function and performance-level measures. This review is limited by the
small number of articles, low-sample sizes and the diversity of devices and their
associated training protocols, and outcome measures. CONCLUSIONS: Preliminary
evidence suggests robot-assisted interventions are safe, feasible and can reduce
active assistance provided by therapists. Implications for rehabilitation Robot
assisted upper extremity training for individuals with cervical spinal cord
injury is safe, feasible and can reduce hands-on assistance provided by
therapists. Future research in robotics rehabilitation with individuals with
spinal cord injury is needed to determine the optimal device and training
protocol as well as effectiveness.
PMID- 29334470
TI - Heterologous Expression of Rhizobial CelC2 Cellulase Impairs Symbiotic Signaling
and Nodulation in Medicago truncatula.
AB - The infection of legume plants by rhizobia is tightly regulated to ensure
accurate bacterial penetration, infection, and development of functionally
efficient nitrogen-fixing root nodules. Rhizobial Nod factors (NF) have key roles
in the elicitation of nodulation signaling. Infection of white clover roots also
involves the tightly regulated specific breakdown of the noncrystalline apex of
cell walls in growing root hairs, which is mediated by Rhizobium leguminosarum
bv. trifolii cellulase CelC2. Here, we have analyzed the impact of this
endoglucanase on symbiotic signaling in the model legume Medicago truncatula.
Ensifer meliloti constitutively expressing celC gene exhibited delayed nodulation
and elicited aberrant ineffective nodules, hampering plant growth in the absence
of nitrogen. Cotreatment of roots with NF and CelC2 altered Ca2+ spiking in root
hairs and induction of the early nodulin gene ENOD11. Our data suggest that CelC2
alters early signaling between partners in the rhizobia-legume interaction.
PMID- 29334471
TI - Special Issue on "Constructing the Self Online".
PMID- 29334472
TI - When Second Life Becomes Real Life: The Evolution of Self-Presentation.
PMID- 29334475
TI - Abandonment of assistive products: assessing abandonment levels and factors that
impact on it.
AB - PURPOSE: To investigate the levels and factors that influence the abandonment of
assistive products by users of a local reference rehabilitation center. METHODS:
This observational study involved users who received services and assistive
products provided by our center of rehabilitation. Users were identified using
the records of the center and their responses about the abandonment were
collected through face-to-face interviews. RESULTS: The abandonment level of
assistive products was 19.38%. 83.5% of the users use at least one of the
assistive products they have received. Rigid and folding frame wheelchairs, with
and without postural support devices, as well as shower wheelchairs, presented
the lowest abandonment levels, followed by canes and lower limb orthoses. Upper
limb orthoses, Knee Ankle Foot Orthosis(KAFO), walkers, crutches and lower and
upper limb prostheses all presented higher abandonment levels. CONCLUSION: The
simultaneous use of mutiple assistive products, users perception on the
importance of using them, and completing the rehabilitation treatment were found
to impact on the short and long-term use of products. The study offers inputs to
decision making and planning for assistive technology provision in developing
countries with regard to expected demand and service delivery. Implications for
Rehabilitation Data about the abandonment of assistive products in Sao Paulo,
Brazil, could assist informing decision making on provision and servicing of
these products in similar settings. The strong correlation found between
abandonment levels and the simultaneous use of multiple devices should be taken
into account by health professionals when prescribing assistive products and
providing guidance to users. The need for follow up on the use of assistive
products after discharge from rehabilitation treatment becomes strikingly clear,
as data show that completing treatment is significantly relevant when evaluating
abandonment levels. As assistive products users' perception about the importance
of using these devices is shown to be significant in explaining abandonment, it
is mandatory that health and rehabilitation professionals take it into account
when providing guidance and training users.
PMID- 29334476
TI - Biological Control of Botrytis cinerea: Interactions with Native Vineyard Yeasts
from Washington State.
AB - Native yeasts are of increasing interest to researchers, grape growers, and
vintners because of their potential for biocontrol activity and their
contributions to the aroma, flavor, and mouthfeel qualities of wines. To assess
biocontrol activity, we tested 11 yeasts from Washington vineyards, representing
isolates of Candida saitoana, Curvibasidium pallidicorallinum, Metschnikowia
chrysoperlae, M. pulcherrima, Meyerozyma guilliermondii, Saccharomyces
cerevisiae, and Wickerhamomyces anomalus, for ability to colonize Thompson
Seedless grape berries, inhibit the growth of Botrytis cinerea in vitro, and
suppress disease symptoms on isolated berries. The yeast-like fungus
Aureobasidium pullulans was also included based on its known biocontrol activity
against B. cinerea in studies on apple and grape. All yeast strains multiplied
rapidly in grape berries and reached densities of over log 6 cells per wound as
early as 2 days after inoculation with 200 cells. One of the Botrytis isolates
used in this study was much less virulent than the others and was provisionally
identified as B. prunorum based on multilocus sequence analysis. Suppression of
the growth of B. cinerea isolates 111bb, 207a, 207cb, and 407cb occurred on
berries treated with A. pullulans P01A006, Metschnikowia chrysoperlae P34A004 and
P40A002, M. pulcherrima P01A016 and P01C004, Meyerozyma guilliermondii P34D003,
and S. cerevisiae HNN11516. Inhibition of Botrytis isolates by the yeast strains
was more common on berries than in vitro, suggesting the possibility that niche
competition was a more likely biocontrol mechanism than antibiosis in planta.
Metabolic profiling of yeast strains and B. cinerea isolates using Biolog YT
plates revealed seven distinct metabolic groups. Furthermore, the yeast strains
showed partial to complete tolerance to the commonly used fungicides fluopyram,
triflumizole, metrafenone, pyraclostrobin, and boscalid. Implications of these
findings for field deployment of native Washington yeasts as biocontrol agents
against B. cinerea are discussed.
PMID- 29334477
TI - Improvement of endothelial function by pitavastatin: a meta-analysis.
AB - OBJECTIVE: Dyslipidemia is commonly associated with endothelial dysfunction and
increased cardiovascular risk. Pitavastatin has been shown to reduce total and
low-density lipoprotein cholesterol, to increase high-density lipoprotein (HDL)
cholesterol and improve HDL function. Furthermore, several trials explored its
effects on flow-mediated dilation (FMD), as an index of endothelial function. The
authors evaluated the effect of pitavastatin therapy on FMD. METHODS: The authors
performed a systematic review and meta-analysis of all clinical trials exploring
the impact of pitavastatin on FMD. The search included PubMed-Medline, Scopus,
ISI Web of Knowledge and Google Scholar databases. Quantitative data synthesis
was performed using a random-effects model, with weighted mean difference (WMD)
and 95% confidence interval (CI) as summary statistics. RESULTS: Six eligible
studies comprising 7 treatment arms were selected for this meta-analysis.
Overall, WMD was significant for the effect of pitavastatin on FMD (2.45%, 95%
CI: 1.31, 3.60, p < 0.001) and the effect size was robust in the leave-one-out
sensitivity analysis. CONCLUSION: This meta-analysis of all available clinical
trials revealed a significant increase of FMD induced by pitavastatin.
PMID- 29334479
TI - Correction: Mobile App-Based Interventions to Support Diabetes Self-Management: A
Systematic Review of Randomized Controlled Trials to Identify Functions
Associated with Glycemic Efficacy.
PMID- 29334478
TI - Authorship Correction: Sampling Key Populations for HIV Surveillance: Results
From Eight Cross-Sectional Studies Using Respondent-Driven Sampling and Venue
Based Snowball Sampling.
AB - [This corrects the article DOI: 10.2196/publichealth.8116.].
PMID- 29334481
TI - Flexible and freestanding supercapacitor based on nanostructured poly(m
aminophenol)/carbon nanofiber hybrid mats with high energy and power densities.
AB - Nanostructured poly(m-aminophenol) (PmAP) coated freestanding carbon nanofiber
(CNF) mats were fabricated through simple in situ rapid-mixing polymerization of
m-aminophenol in the presence of a CNF mat for flexible solid-state
supercapacitors. The surface compositions, morphology and pore structure of the
hybrid mats were characterized by using various techniques, e.g., FTIR, Raman,
XRD, FE-SEM, TEM, and N2 absorption. The results show that the PmAP nanoparticles
were homogeneously deposited on CNF surfaces and formed a thin flexible hybrid
mat, which were directly used to made electrodes for electrochemical analysis
without using any binders or conductive additives. The electrochemical
performances of the hybrid mats were easily tailored by varying the PmAP loading
on a hybrid electrode. The PmAP/CNF-10 hybrid electrode with a relatively low
PmAP loading (> 42 wt%) showed a high specific capacitance of 325.8 F g-1 and a
volumetric capacitance of 273.6 F cm-3 at a current density of 0.5 A g-1,
together with a specific capacitance retention of 196.2 F g-1 at 20 A g-1. The
PmAP/CNF-10 hybrid electrode showed good cycling stability with 88.2% capacitance
retention after 5000 cycles. A maximum energy density of 45.2 Wh kg-1 and power
density of 20.4 kW kg-1 were achieved for the PmAP/CNF-10 hybrid electrode. This
facile and cost-effective synthesis of a flexible binder-free PmAP/CNF hybrid mat
with excellent capacitive performances encourages its possible commercial
exploitation.
PMID- 29334480
TI - Strategies for enhancing medical student resilience: student and faculty member
perspectives.
AB - Objectives: To improve programs aimed to enhance medical student resiliency, we
examined both medical student and faculty advisor perspectives on resiliency
building in an Asian medical school. Methods: In two separate focus groups, a
convenience sample of 8 MD-PhD students and 8 faculty advisors were asked to
identify strategies for enhancing resilience. Using thematic analysis, two
researchers independently examined discussion transcripts and field notes and
determined themes through a consensus process. They then compared the themes to
discern similarities and differences between these groups. Results: Themes from
the student suggestions for increasing resilience included "Perspective changes
with time and experience", "Defining effective advisors," and "Individual paths
to resiliency". Faculty-identified themes were "Structured activities to change
student perspectives," "Structured teaching of coping strategies", and
"Institution-wide social support". Students described themselves as individuals
building their own resilience path and preferred advisors who were not also
evaluators. Faculty, however, suggested systematic, structural ways to increase
resilience. Conclusions: Students and advisors identified some common, and many
distinct strategies for enhancing medical student resilience. Student/advisor
discrepancies may exemplify a cultural shift in Singapore's medical education
climate, where students value increased individualism and autonomy in their
education. As medical schools create interventions to enhance resilience and
combat potential student burnout, they should consider individually-tailored as
well as system-wide programs to best meet the needs of their students and
faculty.
PMID- 29334482
TI - Carbon nanotubes within polymer matrix can synergistically enhance mechanical
energy dissipation.
AB - Safe operation and health of structures relies on their ability to effectively
dissipate undesired vibrations, which could otherwise significantly reduce the
life-time of a structure due to fatigue loads or large deformations. To address
this issue, nanoscale fillers, such as carbon nanotubes (CNTs), have been
utilized to dissipate mechanical energy in polymer-based nanocomposites through
filler-matrix interfacial friction by benefitting from their large interface area
with the matrix. In this manuscript, for the first time, we experimentally
investigate the effect of CNT alignment with respect to reach other and their
orientation with respect to the loading direction on vibrational damping in
nanocomposites. The matrix was polystyrene (PS). A new technique was developed to
fabricate PS-CNT nanocomposites which allows for controlling the angle of CNTs
with respect to the far-field loading direction (misalignment angle). Samples
were subjected to dynamic mechanical analysis, and the damping of the samples
were measured as the ratio of the loss to storage moduli versus CNT misalignment
angle. Our results defied a notion that randomly oriented CNT nanocomposites can
be approximated as a combination of matrix-CNT representative volume elements
with randomly aligned CNTs. Instead, our results points to major contributions of
stress concentration induced by each CNT in the matrix in proximity of other CNTs
on vibrational damping. The stress fields around CNTs in PS-CNT nanocomposites
were studied via finite element analysis. Our findings provide significant new
insights not only on vibrational damping nanocomposites, but also on their
failure modes and toughness, in relation to interface phenomena.
PMID- 29334483
TI - Latanoprost-induced Skin Hypopigmentation.
PMID- 29334484
TI - In Reply: Is the Optic Nerve Head Structure Impacted by a Diagnostic Lumbar
Puncture in Humans?
PMID- 29334485
TI - In Reply: Latanoprost-induced Skin Hypopigmentation.
PMID- 29334486
TI - Is the Optic Nerve Head Structure Impacted by a Diagnostic Lumbar Puncture in
Humans?
PMID- 29334487
TI - A Novel Hinged Scleral Patch Graft for the Repair of Overfiltration and Bleb
Leaks.
AB - INTRODUCTION: The repair of the scleral flap is often needed in cases of severe
hypotony or bleb leaks with overfiltration. We present a simple novel technique
to restore the hinged flap using a scleral patch graft. MATERIALS AND METHODS: We
present 4 eyes of 4 patients who presented with hypotony [intraocular
pressure(IOP) <6 mm Hg] from overfiltration secondary to loose scleral flap (2
eyes) and bleb leak (2 eyes). A scleral patch from a human donor, preserved in
95% ethanol, was cut in a trapezoidal shape and placed over the area of
filtration after a conjunctival peritomy. The scleral graft was secured
anteriorly with a single double-armed 9-0 nylon suture in a double-mattress
manner so as to create a hinged flap. Permanent or releasable sutures were placed
posteriorly to control aqueous outflow. RESULTS: All 4 patients had complete
resolution of hypotony and bleb leaks with increase in their IOP to early teens.
All maintained aqueous flow posteriorly with preservation of bleb function.
CONCLUSION: Reestablishing the original anatomy of the hinged scleral flap can
maintain bleb function without risk of overfiltration or loss of IOP control.
This can be achieved through a simple repair using a scleral patch graft.
PMID- 29334488
TI - Severe Intraocular Pressure Elevation After Intracameral Healon 5 Viscoelastic
Support for Postoperative Hypotony After XEN Gel Stent Insertion.
AB - PURPOSE: The purpose of this article was to describe (i) a novel case of severe
intraocular pressure (IOP) elevation due to intracameral Healon 5 for management
of early postoperative (post-op) hypotony following XEN Gel Stent insertion and
(ii) the management of this complication. MATERIALS AND METHODS: A case report.
RESULTS: A 52-year-old man, with primary open-angle glaucoma and suboptimal left
IOP control on maximally tolerated medical therapy, was managed with XEN Gel
Stent insertion at another tertiary eye unit. Post-op, the IOP was 2 mm Hg with a
shallow anterior chamber (AC) and choroidal effusions. Intracameral injections of
Provisc on post-op days 1 and 3 failed to reverse hypotony. At 1 week post-op,
persistent clinically significant hypotony was managed with Healon 5 injection
into the AC. Twelve hours later, the patient experienced significant pain and
reduced vision and presented to a different tertiary eye unit, where left visual
acuity was hand movements, IOP was 70 mm Hg with a deep AC (complete ophthalmic
viscosurgical device fill with Healon 5) and a flat drainage bleb with no
external drainage. Emergency AC washout of the Healon 5 was performed with
resolution of symptoms, visual acuity, and IOP control. CONCLUSIONS: We caution
against the use of intracameral Healon 5 in the management of post-op hypotony
following XEN Gel Stent insertion, given the potential risk for extreme IOP
elevation and sight loss.
PMID- 29334489
TI - Association between arterial stiffness and wave reflection with subsequent
development of placental-mediated diseases during pregnancy: findings of a
systematic review and meta-analysis.
AB - OBJECTIVE: We present a comprehensive systematic review of published literature
to examine, whether arterial stiffness and wave reflection measurements during
pregnancy differed between healthy patients and patients with placental-mediated
diseases including preeclampsia (PET), small for gestational age (SGA), fetal
death, and placental abruption, and a quantitative assessment of the findings
using the meta-analysis approach. METHODS: We searched Medline, Embase, and The
Cochrane Library for studies of arterial stiffness in pregnancy, analyzed
pregnancy outcomes and conducted the meta-analysis of data evaluated by
trimesters of pregnancy. Hemodynamic parameters evaluated included: pulse wave
velocity (PWV), augmentation index (AIx), and augmentation index-75 (AIx-75).
RESULTS: We screened 2806 citations, reviewed 36 studies and included nine (n =
15 923) studies for further quantitative assessment. Compared with healthy
pregnancy, measures of arterial stiffness and wave reflection were consistently
increased among pregnant women who subsequently developed PET during all
trimesters. In the first trimester, mean AIx-75 (%) in the PET group was
significantly higher with estimated standardized mean difference (SMD) of 0.90
[95% confidence intervals (95% CI) 0.07-1.73; P = 0.034]. In the second
trimester, the PET group had significantly higher PWV (m/s) with estimated SMD of
1.26 (95% CI 0.22-2.30; P = 0.018). Concerning the SGA group, mean AIx (%) was
greater during the second trimester only: 65.5 (SD 15.6) vs. 57.0 (11.2), P <
0.01. CONCLUSION: There is significant increase in arterial stiffness and wave
reflection parameters among pregnant women who subsequently developed PET and SGA
fetuses. Larger studies with consistent methodological designs are required to
evaluate the role and usefulness of arterial stiffness and wave reflection
measurements as a screening tool for placental-mediated diseases during
pregnancy.
PMID- 29334490
TI - Differential impact of local and regional aortic stiffness on left ventricular
remodeling: a cardiovascular magnetic resonance study.
AB - BACKGROUND: Left ventricular (LV) remodeling and aortic stiffness have
independent predictive value for all causes and cardiovascular mortality. Because
elastic properties of the arterial wall vary along the aortic pathway, we
hypothesized that local and regional aortic stiffness could differently impact on
LV remodeling. METHODS AND RESULTS: Regional aortic stiffness was determined from
carotid-femoral pulse wave velocity (cfPWV) measured by aplanation tonometry.
Aortic arch pulse wave velocity was measured by phase contrast cardiovascular
magnetic resonance (CMR). Local stiffness was calculated in the ascending aorta
pulse wave velocity (aaPWV) and descending aorta pulse wave velocity using
central pulse pressure measurement, cine CMR acquisition, and surface change
estimation. CMR LV remodeling was expressed as LV mass to end-diastolic volume
ratio.We evaluated 146 study participants (41 +/- 15 years) free of overt
cardiovascular disease. In stepwise multivariate regression analysis, cfPWV and
aaPWV were significantly and independently correlated to mass to end-diastolic
volume ratio (partial R = 0.07 and R = 0.10, respectively, all P < 0.005) after
adjustment for age, sex, BMI, brachial mean blood pressure, and central pulse
pressure. Descending aorta pulse wave velocity was correlated with mass to end
diastolic volume ratio to a lower extent (R = 0.04, P = 0.0115) and aortic arch
pulse wave velocity was not independently associated with mass to end-diastolic
volume ratio. CfPWV and aaPWV were both independently associated with mass to end
diastolic volume ratio, explaining 5 and 8% of mass to end-diastolic volume ratio
variance, respectively. CONCLUSION: In study participants free of overt
cardiovascular disease, stiffness of the ascending aorta representing the local
proximal aortic function face to the LV and of the downstream aortic pathway
assessed by cfPWV reflecting more advanced alterations of material properties
involving the entire aorta, are independent determinants of LV remodeling after
adjustment to age, BMI, mean blood pressure, and sex.
PMID- 29334491
TI - A randomized titrate-to-target study comparing fixed-dose combinations of
azilsartan medoxomil and chlorthalidone with olmesartan and hydrochlorothiazide
in stage-2 systolic hypertension.
AB - BACKGROUND: Azilsartan medoxomil (AZL-M), an angiotensin II receptor blocker, has
been developed in fixed-dose combinations (FDCs) with chlorthalidone (CTD).
OBJECTIVE/METHODS: We compared FDCs of AZL-M/CTD 20/12.5 mg once daily titrated
to 40/25 mg if needed or AZL-M/CTD 40/12.5 mg once daily titrated to 80/25 mg if
needed with an olmesartan medoxomil (OLM)-hydrochlorothiazide (HCTZ) 20/12.5 mg
FDC once daily titrated to 40/25 mg if needed in a randomized, double-blind, 8
week study of 1085 participants with clinic SBP 160-190 mmHg and DBP 119 mmHg or
less. Titration to higher doses occurred at week 4 if BP was at least 140/90 mmHg
(>=130/80 mmHg if diabetes or chronic kidney disease). The primary endpoint was
change from baseline in clinic SBP; 24-h ambulatory BP monitoring was also
measured. RESULTS: Greater reductions in clinic SBP from a baseline of 165 mmHg
were observed (P < 0.001) in both AZL-M/CTD arms (-37.6 and -38.2 mmHg) versus
OLM/HCTZ (-31.5 mmHg), despite greater dose titration in the OLM/HCTZ group. At 8
weeks, both AZL-M/CTD FDCs reduced 24-h SBP more than OLM/HCTZ (-26.4 and -27.9
versus -20.7 mmHg; both P < 0.001), and higher proportions in both AZL-M/CTD
groups achieved target BP compared with the OLM/HCTZ group (69.4 and 68.9 versus
54.7%, both P < 0.001). Adverse events leading to drug discontinuation occurred
in 6.2, 9.5, and 3.1% with the AZL-M/CTD lower and higher doses, and OLM/HCTZ,
respectively. CONCLUSION: This large, titration-to-target BP study demonstrated
AZL-M/CTD FDCs to have superior antihypertensive efficacy compared with the
maximum approved dose of OLM/HCTZ.
PMID- 29334493
TI - Understanding Severe Maternal Morbidity: Hospital-based Review.
AB - Cases of severe maternal morbidity (SMM) share similarities to maternal deaths,
including increasing in frequency and having similar rates of preventability.
This article will review steps to organizing and implementing standard reviews of
all cases of SMM. These steps include create multidisciplinary SMM review
committee; identify potential SMM cases and confirm true SMM; identify the
morbidity; abstract and summarize data; present case to review committee for
discussion; determine events leading to morbidity; determine opportunities to
improve outcome; assess provider, system and patient factors in cases with
opportunities to improve outcome; make recommendations; and effect change and
evaluate improvement.
PMID- 29334492
TI - Anti-IL-10-mediated Enhancement of Antitumor Efficacy of a Dendritic Cell
targeting MIP3alpha-gp100 Vaccine in the B16F10 Mouse Melanoma Model Is Dependent
on Type I Interferons.
AB - The chemokine MIP3alpha (CCL20) binds to CCR6 on immature dendritic cells.
Vaccines fusing MIP3alpha to gp100 have been shown to be effective in
therapeutically reducing melanoma tumor burden and prolonging survival in a mouse
model. Other studies have provided evidence that interleukin-10 (IL-10)
neutralizing antibodies (alphaIL-10) enhance immunologic melanoma therapies by
modulating the tolerogenic tumor microenvironment. In the current study, we have
utilized the B16F10 syngeneic mouse melanoma model to demonstrate for the first
time that a therapy neutralizing IL-10 enhances the antitumor efficacy of a
MIP3alpha-gp100 DNA vaccine, leading to significantly smaller tumors, slower
growing tumors, and overall increases in mouse survival. The additive effects of
alphaIL-10 were not shown to be correlated to vaccine-specific tumor-infiltrating
lymphocytes (TILs), total TILs, or regulatory T cells. However, we discovered an
upregulation of IFNalpha-4 transcripts in tumors and a correlation of increased
plasmacytoid dendritic cell numbers with reduced tumor burden in alphaIL-10
treated mice. Interferon alpha receptor knockout (IFNalphaR1) mice received no
benefit from alphaIL-10 treatment, demonstrating that the additional therapeutic
value of alphaIL-10 is primarily mediated by type I IFNs. Efficient targeting of
antigen to immature dendritic cells with a chemokine-fusion vaccine provides an
effective anticancer therapeutic. Combining this approach with an IL-10
neutralizing antibody therapy enhances the antitumor efficacy of the therapy in a
manner dependent upon the activity of type I IFNs. This combination of a vaccine
and immunomodulatory agent provides direction for future optimization of a novel
cancer vaccine therapy.
PMID- 29334494
TI - State-based Review of Maternal Deaths: The Ohio Experience.
AB - Ohio established a Pregnancy-Associated Mortality Review system in 2010 to ensure
that all maternal deaths are identified and preventive actions developed. The
need for detailed and reliable information to supplement vital statistics data
has led to the development of state-based and urban-based maternal death reviews.
Although processes vary from state to state, in general, an expert panel is
convened to review individual cases and make recommendations for systems change.
This article describes the development and operation of Ohio's state-based
maternal death review including interventions developed and actions taken based
on review data.
PMID- 29334495
TI - The ethics of interventional procedures for patients too ill for surgery.
AB - PURPOSE OF REVIEW: Minimally invasive interventional procedures are increasingly
popular options for patients who are high-risk candidates for open surgical
procedures. It is unclear how to proceed in the rare circumstance of a
complication during an interventional procedure, where addressing the
complication would require exposing the patient to the full risk that was being
avoided with the minimally invasive technique. This review provides
recommendations on how to approach this paradoxical scenario. RECENT FINDINGS:
Risk stratification, communication frameworks, and advanced care planning can
facilitate shared decision-making between physicians and patients. Risk
stratification may include mortality predictive models, disability and frailty
scores, and patient-centered outcome studies. In the event of procedural
complication or failure, aggressive surgical treatment or limited repair should
be guided by patient preferences to best ensure value concordant care. SUMMARY:
Interventional procedures, and emergent open surgery, should be offered as long
as patients are fully informed about the benefits and risks, including the
implications of potential life-sustaining treatments, and whether their
respective goals of treatment are consistent with the intervention. Implementing
this framework will require a cultural shift in physician attitudes to recognize
that in some cases, nonintervention or less aggressive treatment may be a
reasonable alternative to surgical intervention.
PMID- 29334496
TI - Oxygen in the critically ill: friend or foe?
AB - PURPOSE OF REVIEW: To examine the potential harmful effects of hyperoxia and
summarize the results of most recent clinical studies evaluating oxygen therapy
in critically ill patients. RECENT FINDINGS: Excessive oxygen supplementation may
have detrimental pulmonary and systemic effects because of enhanced oxidative
stress and inflammation. Hyperoxia-induced lung injury includes altered
surfactant protein composition, reduced mucociliary clearance and histological
damage, resulting in atelectasis, reduced lung compliance and increased risk of
infections. Hyperoxemia causes vasoconstriction, reduction in coronary blood flow
and cardiac output and may alter microvascular perfusion. Observational studies
showed a close relationship between hyperoxemia and increased mortality in
several subsets of critically ill patients. In absence of hypoxemia, the routine
use of oxygen therapy in patients with myocardial infarction, stroke, traumatic
brain injury, cardiac arrest and sepsis, showed no benefit but rather it seems to
be harmful. In patients admitted to intensive care unit, a conservative oxygen
therapy aimed to maintain arterial oxygenation within physiological range has
been proved to be well tolerated and may improve outcome. SUMMARY: Liberal O2 use
and unnecessary hyperoxia may be detrimental in critically ill patients. The
current evidence supports the use of a conservative strategy in O2 therapy to
avoid patient exposure to unnecessary hyperoxemia.
PMID- 29334497
TI - Deep vein thrombosis and venous thromboembolism in trauma.
AB - PURPOSE OF REVIEW: Deep vein thrombosis (DVT) and pulmonary embolus are major
causes of hospital-related morbidity and mortality, and are recognized as
complications in patients with traumatic injury. Despite the significant
morbidity and mortality associated with DVTs, prophylaxis and treatment are still
not well understood and remain the subject of research and debate. RECENT
FINDINGS: Elements of the patient's history and physical examination, along with
thromboelastography, can be used to predict patients who are at greatest risk of
DVT and venous thromboembolism (VTE). Novel assays and biomarkers hold promise
for more accurate evaluation of coagulation status. Patients with traumatic
injury are routinely treated with either mechanical or pharmacological treatments
to prevent DVT, and a growing body of evidence suggests that DVT prophylaxis
should be initiated as early as possible in a patient's hospital course. SUMMARY:
In trauma patients with traumatic injury, early identification and targeted VTE
prophylaxis in trauma patients may prevent this life-threatening complication.
PMID- 29334498
TI - Evidence-based Interpretation of Amyloid-beta PET Results: A Clinician's Tool.
AB - BACKGROUND: Amyloid-beta positron emission tomography (PET) allows for in vivo
detection of fibrillar amyloid plaques, a pathologic hallmark of Alzheimer's
disease (AD). However, amyloid-beta PET interpretation is limited by the
imperfect correlation between PET and autopsy, and the fact that it is positive
in about 20% to 30% of cognitively normal individuals and non-AD dementias,
especially when older or carrying the epsilon4 allele of apolipoprotein E
(ApoE4). When facing a positive amyloid PET, clinicians have to evaluate the
probability of a pathologic false positive as well as the probability of amyloid
positivity being age-related, comorbid to a primary non-AD dementia
(clinicopathologic false positive). These probabilities can be calculated to
reach an evidence-based interpretation of amyloid-beta. As literature review and
calculations cannot be easily performed in the day-to-day clinic, we propose a
clinician friendly, evidence-based Bayesian approach to the interpretation of
amyloid-beta PET results in the differential diagnosis of patients with cognitive
impairment. METHODS: We defined AD as a clinicopathologic entity in which amyloid
beta is the primary cause of cognitive impairment. We systematically reviewed the
literature to estimate the sensitivity and specificity of amyloid-beta PET
against neuropathologic examination. We inferred rates of clinicopathologic false
positivity (non-AD dementia with comorbid amyloid) based on age-dependent and
ApoE-dependent prevalence of amyloid positivity in normal individuals and AD
patients provided in large meta-analyses published by the Amyloid Biomarker Study
Group. We calculated positive predictive value (PPV) and negative predictive
value (NPV) of amyloid-beta PET, which are presented in a clinician-friendly
table. RESULTS: PPV of PET is highest in young ApoE4- patients with high pre-PET
probability of AD. In older ApoE4+ patients with low pre-PET probability of AD,
positive amyloid-beta PET scans must be interpreted with caution. A negative
amyloid-beta PET makes a diagnosis of AD unlikely except in old patients with
high pre-PET probability of AD. CONCLUSION: This evidence-based approach might
provide guidance to clinicians and nuclear medicine physicians to interpret
amyloid-beta PET results for early and differential diagnosis of patients with
progressive cognitive impairment.
PMID- 29334499
TI - Cognitive Function and its Risk Factors Among Older US Adults Living at Home.
AB - BACKGROUND: The Montreal Cognitive Assessment (MoCA) has not been administered to
a representative national sample, precluding comparison of patient scores to the
general population and for risk factor identification. METHODS: A validated
survey-based adaptation of the MoCA (MoCA-SA) was administered to a probability
sample of home-dwelling US adults aged 62 to 90, using the National Social Life,
Health, and Aging Project (n=3129), yielding estimates of prevalence in the
United States. The association between MoCA-SA scores and sociodemographic and
health-related risk factors were determined. RESULTS: MoCA-SA scores decreased
with age, and there were substantial differences among sex, education, and
race/ethnicity groups. Poor physical health, functional status, and depression
were also associated with lower cognitive performance; current health behaviors
were not. Using the recommended MoCA cut-point score for Mild Cognitive
Impairment (MoCA score <26; MoCA-SA score <17), 72% (95% confidence interval, 69%
to 74%) of older US adults would be classified as having some degree of cognitive
impairment. CONCLUSIONS: Our results provide an important national estimate for
interpreting MoCA scores from individual patients, and establish wide variability
in cognition among older home-dwelling US adults. Care should be taken in
applying previously-established MoCA cut-points to the general population,
especially when evaluating individuals from educationally and ethnically diverse
groups.
PMID- 29334500
TI - Overexpression of u-Opioid Receptors in Peripheral Afferents, but Not in
Combination with Enkephalin, Decreases Neuropathic Pain Behavior and Enhances
Opioid Analgesia in Mouse.
AB - BACKGROUND: The current study used recombinant herpes simplex virus type I to
increase expression of u-opiate receptors and the opioid ligand preproenkephalin
in peripheral nerve fibers in a mouse model of neuropathic pain. It was predicted
that viral vector delivery of a combination of genes encoding the u-opioid
receptor and preproenkephalin would attenuate neuropathic pain and enhance opioid
analgesia. The behavioral effects would be paralleled by changes in response
properties of primary afferent neurons. METHODS: Recombinant herpes simplex virus
type 1 containing cDNA sequences of the u-opioid receptor, human
preproenkephalin, a combination, or Escherichia coli lacZ gene marker (as a
control) was used to investigate the role of peripheral opioids in neuropathic
pain behaviors. RESULTS: Inoculation with the u-opioid receptor viral vector (n =
13) reversed mechanical allodynia and thermal hyperalgesia and produced leftward
shifts in loperamide (ED50 = 0.6 +/- 0.2 mg/kg vs. ED50 = 0.9 +/- 0.2 mg/kg for
control group, n = 8, means +/- SD) and morphine dose-response curves (ED50 = 0.3
+/- 0.5 mg/kg vs. ED50 = 1.1 +/- 0.1 mg/kg for control group). In u-opioid
receptor viral vector inoculated C-fibers, heat-evoked responses (n = 12) and
ongoing spontaneous activity (n = 18) were decreased after morphine application.
Inoculation with both u-opioid receptor and preproenkephalin viral vectors did
not alter mechanical and thermal responses. CONCLUSIONS: Increasing primary
afferent expression of opioid receptors can decrease neuropathic pain-associated
behaviors and increase systemic opioid analgesia through inhibition of peripheral
afferent fiber activity.
PMID- 29334501
TI - Practice Guidelines for Moderate Procedural Sedation and Analgesia 2018: A Report
by the American Society of Anesthesiologists Task Force on Moderate Procedural
Sedation and Analgesia, the American Association of Oral and Maxillofacial
Surgeons, American College of Radiology, American Dental Association, American
Society of Dentist Anesthesiologists, and Society of Interventional Radiology.
PMID- 29334502
TI - Risk of Hepatitis B Virus Reactivation Among Patients Treated With Ledipasvir
Sofosbuvir for Hepatitis C Virus Infection.
AB - BACKGROUND: Direct acting antiviral (DAA) agents are the standard of care for
treatment of hepatitis C virus (HCV)-infected individuals. Hepatitis B virus
(HBV) reactivation during HCV treatment has been reported, the incidence and
clinical outcome remains unclear. The aim of our study is to examine the risk of
HBV reactivation in actively infected or previously exposed patients during or
after HCV treatment with DAAs. METHODS: Adults with chronic HCV infection
previously exposed or actively infected with HBV and treated with DAAs between
December 2015 to 2016 were included. Electronic medical records were reviewed for
HCV treatment dates, HCV treatment response, DAA used, HBV status, and concurrent
HBV treatment. Primary end-point was to determine the risk of HBV reactivation
during or up to 3 months after DAA treatment. RESULTS: We identified 283
patients, and 100% of patients completed HCV treatment with ledipasvir
sofosbuvir. 93% had HCV genotype-1 of whom 91% achieved sustained viral response
at 12 weeks posttreatment (SVR-12). In total, 7% had HCV genotype-4 who achieved
SVR-12 of 84%. Mean (+/-SD) age was 59.7 (+/-7) years, and 58% were male. A total
of 45% of patients had hepatitis B core antibody (HBcAb) positive and hepatitis B
surface antigen (HBsAg) negative. In total, 55% of patients had a positive HBsAg
before HCV DAA treatment. No HBV reactivation was encountered in the (HBcAb)
positive HBsAg-negative cohort nor in the (HBsAg) positive group with 95%
confidence interval (0-0.023) and (0-0.019), respectively. CONCLUSION: In our
study of patients with HCV and isolated hepatitis B core or HBsAg positivity, no
HCV patients treated with DAA experienced HBV reactivation.
PMID- 29334503
TI - Family history of autoimmune diseases and risk of gastric cancer: a national
cohort study.
AB - A personal history of autoimmune diseases is associated with an increased
incidence of gastric cancer, but whether they share familial susceptibility is
still unknown. The contribution of shared environmental or genetic factors toward
the observed familial aggregation has not been determined. We used a few Swedish
registers, including the Swedish Multigeneration Register and the Cancer
Register, to examine the familial risk of gastric cancer among individuals with a
family history of a set of autoimmune diseases. Standardized incidence ratios
were used to calculate the relative risk. The overall risk of gastric cancer was
1.22 (95% confidence interval: 1.14-1.30) among individuals with a sibling
affected with any of the 33 autoimmune diseases. For specific disease, siblings
of individuals with Crohn's diseases, diabetes type 1, Graves'/hyperthyroidism,
myasthenia gravis, psoriasis, rheumatoid arthritis, sarcoidosis, and uncreative
colitis showed an association with an increased incidence of gastric cancer, with
a standardized incidence ratio ranging between 1.17 and 1.64. Familial
aggregation was found only for corpus cancer. No association was observed between
spouses. Gastric cancer, mainly corpus cancer, shares familial susceptibility
with a few autoimmune diseases, suggesting that shared genetic polymorphisms may
contribute toward both Helicobacter pylori infection and autoimmune diseases.
PMID- 29334504
TI - Bradykinin receptors gene expression in white adipose tissue in nondiabetic
patients with coronary artery disease.
AB - OBJECTIVES: Adipose tissue plays a key role in cardiovascular physiology. Kinin
receptors are important determinant of the effect of adiposity on endothelial
function and cardiovascular function. We examined the gene expression levels of
kinin receptors in the subcutaneous white adipose tissue (sWAT) of nondiabetic
patients with and without coronary artery disease (CAD). PATIENTS AND METHODS: We
evaluated 21 patients with CAD (13 men, age: 68+/-8 years) and 23 patients
without CAD (15 men, age: 66+/-5 years) who underwent catheterization through the
femoral route. sWAT biopsies were obtained from the site of vessel puncture
before the procedure and analyzed for bradykinin receptor type 1 (BKR1) and 2
(BKR2) gene expression by real-time quantitative PCR. RESULTS: Although BKR2
expression levels did not differ significantly (413.12+/-532.41 in CAD patients
vs. 378.33+/-534.45 in controls, P=NS), BKR1 expression in sWAT was significantly
greater in patients with CAD (352.69+/-455.12 vs. 46.5+/-46.7, P<0.05). Notably,
BKR1 gene expression levels showed a significant positive correlation with BMI
(r=0.45, P<0.002) and total cholesterol levels (r=0.53, P<0.001), and a negative
correlation with fasting blood glucose (r=-0.4, P=0.006). CONCLUSION: There is a
divergence in BKR1 gene expression in sWAT between patients with and without CAD
and is associated with metabolic parameters. More studies are needed to determine
the pathophysiological role of BKRs in adipogenesis, fat expansion, and
atheromatous disease.
PMID- 29334505
TI - The association of chronic air pollutants with coronary artery spasm, vasospastic
angina, and endothelial dysfunction.
AB - BACKGROUND: We evaluated the effect of chronic exposure to air pollutants (APs)
on coronary endothelial function and significant coronary artery spasm (CAS) as
assessed by intracoronary acetylcholine (ACH) provocation test. PATIENTS AND
METHODS: A total of 6430 patients with typical or atypical chest pain who
underwent intracoronary ACH provocation test were enrolled. We obtained data on
APs from the Korean National Institute of Environmental Research
(http://www.nier.go.kr/). APs are largely divided into two types: particulate
matter with aerodynamic diameter of less than or equal to 10 um in size (PM10)
and gaseous pollutants such as nitrogen dioxide, sulfur dioxide, carbon monoxide,
and ozone. The primary endpoint is the incidence of significant CAS and its
associated parameters during ACH provocation test. RESULTS: The incidence of CAS
was positively correlated with an exposure duration of PM10, whereas nitrogen
dioxide, sulfur dioxide, carbon monoxide, and ozone were shown to be unrelated to
CAS. During the ACH provocation test, as PM10 increased, the frequency of CAS was
increased, and the incidence of transient ST-segment elevation was also
increased. There was a trend toward higher incidence of spontaneous spasm as PM10
increased. The mean exposure level of PM10 was 51.3+/-25.4 ug/m. The CAS risk
increased by 4% when the level of PM10 increased by 20 ug/m by an adjusted Cox
regression analysis. CONCLUSION: CAS incidence is closely related to exposure to
PMs but not to gaseous pollutants. Particularly, higher exposure concentrations
and longer exposure duration of PM10 increased the risk of CAS. These important
findings provide a plausible mechanism that links air pollution to vasospastic
angina and provide new insights into environmental factors.
PMID- 29334507
TI - What's hot in heart valve disease 2018?
PMID- 29334506
TI - Targeted biopsy: benefits and limitations.
AB - PURPOSE OF REVIEW: To review the current literature regarding the role of
multiparametric MRI and fusion-guided biopsies in urologic practice. RECENT
FINDINGS: Fusion biopsies consistently show an increase in the detection of
clinically significant cancers and decrease in low-risk disease that may be more
suitable for active surveillance. Although, when to incorporate multiparametric
MRI into workup is not clearly agreed upon, studies have shown a clear benefit in
both biopsy naive and those with prior negative biopsies in determining the
appropriate treatment strategy. More recently, cost-analysis models have been
published that show that upfront MRIs are more cost-effective when considering
missed cancers and treatment courses. SUMMARY: With improved accuracy over
systematic biopsies, fusion biopsies are a superior method for detection of the
true grade of cancer for both biopsy naive and patients with prior negative
biopsies, choosing appropriate candidates for active surveillance, and monitoring
progression on active surveillance.
PMID- 29334508
TI - Practical valvular issues in patients requiring ventricular assist devices.
AB - PURPOSE OF REVIEW: As ventricular assist device (VAD) therapy in patients with
advanced heart failure continues to grow, experience with concomitant valvular
diseases present either before or after VAD implantation continues to accrue. In
this review, we discuss recent data and current practice as it pertains to the
subject of concomitant valvular disease in patients requiring VADs. RECENT
FINDINGS: Persistent aortic valve closure has been identified as a potential
contributor to aortic valve 'disuse atrophy' resulting in valve degeneration.
Dilation of the aortic root may be predictive of future development of aortic
insufficiency. Novel echocardiographic parameters to identify the severity of
aortic insufficiency following VAD implantation may be useful for risk
stratification. Concomitant repair of significant mitral regurgitation may confer
benefit to pulmonary vascular resistance and right ventricular function; however,
this remains controversial. Concomitant repair of significant tricuspid
regurgitation has not demonstrated early postoperative benefit nor survival
benefit. Atrial fibrillation has emerged as a risk factor that may predict
accelerated progression of postoperative tricuspid regurgitation. SUMMARY:
Management of aortic insufficiency, mitral regurgitation or tricuspid
regurgitation in patients requiring VADs continues to be the source of
controversy. As experience accrues with varying strategies to prevent or manage
these valvular lesions, our understanding of the impact of these strategies
continues to evolve.
PMID- 29334509
TI - Comparison of Stress and Strain Distribution Around Splinted and Nonsplinted 6-mm
Short Implants in Posterior Mandible: A Finite Element Analysis Study.
AB - PURPOSE: This study was designed to compare the biomechanical performance of
splinted and nonsplinted short implants, in the posterior mandible, using finite
element analysis. MATERIALS AND METHODS: Three-dimensional models of short
implants with 2 different diameters (4 * 6 mm or 5 * 6 mm) were scanned, and
CATIA (R21) was used to simulate the model of an edentulous lower jaw.
Experimental groups were designed as follows: (1) D4L6-splinted (three 4 * 6-mm
splinted implants), (2) D4L6-nonsplinted, (3) D5L6-splinted, and (4) D5L6
nonsplinted. A 100 N load was applied, and stress and strain values in
surrounding bone were analyzed in specific nodes using ANSYS software (16.1).
RESULTS: The maximum stress values under axial load were found in D5L6-splinted
model, and under oblique load, D5L6-nonsplinted model had the maximum stress
values. Under axial load, D4L6-splinted model showed maximum strain values, but
when oblique load was applied, D4L6-nonsplinted model had the maximum strain
values. CONCLUSION: Splinting adjacent short implants may provide less bone
strain and stress, especially at the presence of lateral forces. Increasing the
implant diameter may be effective in strain reduction, but does not seem to
reduce the bone stress, regardless of the direction of the load applied.
PMID- 29334510
TI - Comparing peri-operative complications of paediatric and adult anaesthesia: A
retrospective cohort study of 81 267 cases.
AB - BACKGROUND: Comparisons of peri-operative complications associated with
paediatric (<=16 years) and adult anaesthesia are poorly available, especially in
which cardiac surgery, organ transplantation and neurosurgery are involved.
OBJECTIVE: The aim of this study was to evaluate the nature and incidence of peri
operative complications that might be due to anaesthesia and to identify
independent risk factors for complications in children and adults, including
those undergoing cardiac surgery, organ transplantation and neurosurgery. DESIGN:
Retrospective cohort study. SETTING: The study was performed at the University
Medical Centre Groningen in the 4 years between 1 January 2010 and the 31
December 2013. MAIN OUTCOME MEASURES: Complications and their severity were
graded according to the standard complication score (20 items) of the Dutch
Society of Anaesthesia. Univariate and multivariate regression analysis was used
to identify independent risk factors for the reported complications. RESULTS: A
total of 81 267 anaesthetic cases were included. In the paediatric cohort, there
were 410 (2.9%) complications and 1675 (2.5%) in the adults. In both cohorts age,
American Society of Anaesthesiologists classification and emergency treatment
were independent risk factors for complications. With respect to age, infants
less than 1 year were at the highest risk, whereas in the adult cohort, increased
age was related to a greater number of complications. The incidences of the
specific complications were different between both cohorts. Upper airway
obstruction was more frequently observed in paediatric patients (26%), whereas in
the adults, complications with the highest incidence concerned conversion of
regional-to-general anaesthesia (25%) and hypotension (17%). CONCLUSION: Risk
factors for all peri-operative complications were similar for paediatric and
adult anaesthesia. However, the incidence of specific complications differed
between both age categories.
PMID- 29334511
TI - Evaluation of recombinant factor VIIa, tranexamic acid and desmopressin to reduce
prasugrel-related bleeding: A randomised, placebo-controlled study in a rabbit
model.
AB - BACKGROUND: Prasugrel is a thienopyridine that inhibits platelet aggregation more
rapidly and effectively than clopidogrel, with an increased bleeding risk.
OBJECTIVE: The current study aimed to evaluate the efficacy of three nonspecific
haemostatic drugs - recombinant activated factor VII (rFVIIa), tranexamic acid
and desmopressin (DDAVP) - to limit blood loss after administration of prasugrel
in a rabbit model of bleeding while also evaluating any prothrombotic effects.
DESIGN: Randomised, placebo-controlled study. SETTING: Faculty of Medicine,
University of Geneva, Switzerland, in 2013. ANIMALS: Anaesthetised and
artificially ventilated rabbits (n=56). INTERVENTIONS: Animals were randomly
allocated to one of five groups: control (placebo-placebo), prasugrel-placebo,
rFVIIa (prasugrel-rFVIIa 150 MUg kg), tranexamic acid (prasugrel-tranexamic acid
20 mg kg) or DDAVP (prasugrel-DDAVP 1 MUg kg). Two hours after an oral prasugrel
loading dose (4 mg kg), a stenosis and an injury were inflicted on the carotid
artery to induce cyclic flow reductions (CFRs) due to thrombosis. Haemostatic
drugs were administered during the ensuing observation period. MAIN OUTCOME
MEASURES: Standardised hepatosplenic sections were performed to evaluate the
primary endpoint of blood loss, monitored for 15 min. Ear-immersion bleeding time
and incidence of CFRs were secondary endpoints. RESULTS: Prasugrel decreased ADP
induced platelet aggregation (light transmission method) from 66 +/- 4% (mean +/-
SD) to 41 +/- 7% (P < 0.001) and doubled blood loss: 10.7 g (10.1 to12.7) [median
(interquartile range)] vs. 20.0 g (17.0 to 24.4), P = 0.003 in the control and
prasugrel-placebo groups, respectively. rFVIIa, tranexamic acid and DDAVP reduced
neither hepatosplenic blood loss [19.7 g (14.0 to 27.6), 25.2 g (22.6 to 28.7)
and 22.9 g (16.8 to 28.8), respectively] nor bleeding time compared with placebo.
Regarding safety, rVIIa induced three or more CFRs in 5/12 rabbits, vs. 0/12 in
the prasugrel-placebo group (P = 0.037), whereas tranexamic acid and DDAVP did
not increase them. CONCLUSION: The three studied haemostatic drugs rFVIIa,
tranexamic acid and DDAVP failed to reduce prasugrel-related bleeding in this
model. rFVIIa-treated rabbits were more prone to arterial thrombotic events.
TRIAL REGISTRATION: NA.
PMID- 29334513
TI - Opioid Use Disorders Attributed to Tramadol Among Egyptian University Students.
AB - BACKGROUND: Tramadol use is an overwhelming problem in Egypt with tremendous
medical and social consequences especially among youth. Use liability among
Egyptian university students is underevaluated. This study aimed to estimate the
prevalence and associated correlates of tramadol use among students from Zagazig
University, Egypt. METHODS: A cross-sectional study included a total of 1135
undergraduate students, from 10 colleges in Zagazig University. Participants were
randomly selected and assessed for tramadol use using The Drug Use Disorders
Identification Test (DUDIT) and The Drug Use Disorders Identification Test
Extended (DUDIT-E). RESULTS: The prevalence of tramadol use was 12.3% among
university students, with higher prevalence in male (20.2%) than female students
(2.4%). The average age at onset of tramadol use was 17.6 +/- 2.1. Only 15% of
the students with substance use were using tramadol alone whereas the rest (85%)
were using at least 1 drug plus tramadol. One-fifth of these students started
with tramadol as their first drug. Smoking, cannabis, and alcohol use predict
tramadol use. About 60% of students who use tramadol had drug-related problems
and 30% had dependence. Treatment readiness for tramadol use is negatively
correlated with smoking and its duration. CONCLUSIONS: Tramadol use was common
among university students, with higher prevalence among males. There is a
considerable relationship between tramadol use, smoking, and use of other
substances. Further population-based longitudinal studies need to investigate the
causal relationship between tramadol use, smoking, and use of other substances.
PMID- 29334512
TI - Association Between Alcohol Use and Angina Symptoms Among Outpatients From the
Veterans Health Administration.
AB - BACKGROUND: Alcohol use is associated with angina incidence, but associations
between alcohol use and experience of angina among patients with coronary artery
disease (CAD) have not been described. METHODS: Outpatients with CAD from 7
clinics in the Veterans Health Administration were surveyed; alcohol use was
measured using the validated Alcohol Use Disorders Identification Test
Consumption scores categorized into 6 groups: nondrinking, low-risk drinking, and
mild, moderate, severe, and very severe unhealthy alcohol use. Three domains of
self-reported angina symptoms (frequency, stability, and physical function) were
measured with the Seattle Angina Questionnaire. Linear regression models
evaluated associations between alcohol use groups and angina symptoms. Models
were adjusted first for age and then additionally for smoking, comorbidities, and
depression. RESULTS: Patients (n = 8303) had a mean age of 66 years. In age
adjusted analyses, a U-shaped association was observed between alcohol use groups
and all angina outcomes, with patients in nondrinking and severe unhealthy
alcohol groups reporting the greatest angina symptoms and lowest functioning.
After full adjustment, no clinically important and few statistically important
differences were observed across alcohol use in angina stability or frequency.
Patients in the nondrinking group had statistically greater functional limitation
from angina than those in all groups of unhealthy alcohol use, though differences
were small. Patients in all groups of unhealthy alcohol use did not differ
significantly from those with low-risk drinking. CONCLUSIONS: Alcohol use was
associated with some small statistically but no clinically important differences
in angina symptoms among patients with CAD. This cross-sectional study does not
support a protective effect of low-level drinking on self-reported angina.
PMID- 29334514
TI - Monitoring Depression Rates in an Urban Community: Use of Electronic Health
Records.
AB - OBJECTIVES: Depression is the most common mental health disorder and mediates
outcomes for many chronic diseases. Ability to accurately identify and monitor
this condition, at the local level, is often limited to estimates from national
surveys. This study sought to compare and validate electronic health record (EHR)
based depression surveillance with multiple data sources for more granular
demographic subgroup and subcounty measurements. DESIGN/SETTING: A survey
compared data sources for the ability to provide subcounty (eg, census tract
[CT]) depression prevalence estimates. Using 2011-2012 EHR data from 2 large
health care providers, and American Community Survey data, depression rates were
estimated by CT for Denver County, Colorado. Sociodemographic and geographic
(residence) attributes were analyzed and described. Spatial analysis assessed for
clusters of higher or lower depression prevalence. MAIN OUTCOME MEASURE(S):
Depression prevalence estimates by CT. RESULTS: National and local survey-based
depression prevalence estimates ranged from 7% to 17% but were limited to county
level. Electronic health record data provided subcounty depression prevalence
estimates by sociodemographic and geographic groups (CT range: 5%-20%). Overall
depression prevalence was 13%; rates were higher for women (16% vs men 9%),
whites (16%), and increased with age and homeless patients (18%). Areas of higher
and lower EHR-based, depression prevalence were identified. CONCLUSIONS:
Electronic health record-based depression prevalence varied by CT, gender,
race/ethnicity, age, and living status. Electronic health record-based
surveillance complements traditional methods with greater timeliness and
granularity. Validation through subcounty-level qualitative or survey approaches
should assess accuracy and address concerns about EHR selection bias. Public
health agencies should consider the opportunity and evaluate EHR system data as a
surveillance tool to estimate subcounty chronic disease prevalence.
PMID- 29334515
TI - Facilitating Adoption of an Electronic Documentation System.
AB - Best practice recommends the integration of clinical documentation into the
hospital electronic health record to support safe, efficient, and timely patient
care. A major barrier to successful adoption and optimization of computerized
documentation systems is user satisfaction. The purpose of this descriptive,
performance improvement initiative was to implement and evaluate user
satisfaction with an electronic documentation system to facilitate successful
adoption. The Clinical Procedure Flowsheets application was implemented in a
geriatric extended care unit of a large healthcare system. Rogers' Diffusion of
Innovation and Davis' Technology Acceptance Model were used to guide system
adoption and improve user experience of the innovation. The Perceived Usefulness
and Perceived Ease of Use questionnaire was distributed to 24 nursing staff
working in the unit 9 weeks after implementation. Results indicated that
respondents perceived the Clinical Procedure Flowsheets as easy to use and useful
in accomplishing their documentation tasks. The overall mean satisfaction score
of 72.17 (SD, 12.13) implied a strong level of user acceptance. The positive
perception of the nursing staff in the geriatric extended care unit suggests a
high probability of system use that can enhance the documentation of patient
care. Further research is recommended to evaluate factors related to system
adoption and user satisfaction.
PMID- 29334516
TI - Computer-Based Training in Eating and Nutrition Facilitates Person-Centered
Hospital Care: A Group Concept Mapping Study.
AB - Studies have shown that computer-based training in eating and nutrition for
hospital nursing staff increased the likelihood that patients at risk of
undernutrition would receive nutritional interventions. This article seeks to
provide understanding from the perspective of nursing staff of conceptually
important areas for computer-based nutritional training, and their relative
importance to nutritional care, following completion of the training. Group
concept mapping, an integrated qualitative and quantitative methodology, was used
to conceptualize important factors relating to the training experiences through
four focus groups (n = 43), statement sorting (n = 38), and importance rating (n
= 32), followed by multidimensional scaling and cluster analysis. Sorting of 38
statements yielded four clusters. These clusters (number of statements) were as
follows: personal competence and development (10), practice close care
development (10), patient safety (9), and awareness about the nutrition care
process (9). First and second clusters represented "the learning organization,"
and third and fourth represented "quality improvement." These findings provide a
conceptual basis for understanding the importance of training in eating and
nutrition, which contributes to a learning organization and quality improvement,
and can be linked to and facilitates person-centered nutritional care and patient
safety.
PMID- 29334517
TI - The effect of arthropathies on illness perceptions, coping strategies, outcomes,
and their changes over time in patients with inflammatory bowel disease: a 12
month follow-up study.
AB - OBJECTIVES: Arthropathies are a common extraintestinal manifestation (EIM) in
inflammatory bowel disease (IBD). This study evaluated the differences in illness
perceptions, coping strategies, and illness outcomes between patients with IBD
with and without arthropathies at baseline and examined changes at 12 months in
these variables in patients with arthropathies. METHODS: In total, 204 patients
with (n=123) and without (n=81) arthropathies completed questionnaires at
baseline and after 1 year, assessing illness perceptions, coping strategies,
quality of life, and work and activity impairment. A linear regression analysis
assessed the effect of arthropathies on these factors compared with patients
without arthropathies. A mixed model analysis evaluated changes in illness
perceptions, coping strategies, and outcomes in patients with arthropathies over
time. RESULTS: Patients with arthropathies had more persistent thoughts on
symptomatology and the variability of symptoms, held more negative views on the
effects of illness, had heightened emotions that affected daily functioning, and
had a poorer understanding of IBD than patients without arthropathies. Patients
with arthropathies could more efficiently divert attention, felt more useful to
others, and perceived a reduced physical and mental health and an increased
activity impairment compared with patients without arthropathies. At follow-up,
patients with arthropathies were more sceptical about the effectiveness of
medical treatment but were better able to adapt their activities to their
complaints compared with baseline. CONCLUSION: Patients with arthropathies in IBD
adopt different illness perceptions and coping strategies and have different
outcomes compared with patients without arthropathies, which is important to know
when designing behavioral and physical interventions to improve functioning.
PMID- 29334518
TI - Is ileocecal valve intubation essential for routine colonoscopic examination?
AB - BACKGROUND: In this study, we aimed to assess the diagnostic yield of terminal
ileum intubation during routine colonoscopy. MATERIALS AND METHODS: We routinely
performed terminal ileum intubation in all patients who underwent colonoscopy at
Dokuz Eylul University Hospital between February 2014 and June 2015. Two
gastroenterology fellows performed colonoscopies in the Central Endoscopy Unit.
Demographic data of patients, indications of colonoscopies, cecum and ileum
intubation rate/time, and endoscopic and histopathologic findings of the terminal
ileum were all assessed. RESULTS: A total of 1310 consecutive patients (726
female and 584 male, median age: 55.79+/-14.29 years) underwent colonoscopy
during this study period. The colonoscopy was successfully completed in 1144
(87.3%) cases. The terminal ileum was successfully intubated in 1032 (90.2%)
cases. The mean time taken to reach the ileum from the cecum was 63.08+/-64.16 s.
Endoscopic abnormalities on the terminal ileum were present in 62 (6%) cases, and
biopsies were taken from these patients. However, endoscopic abnormalities were
found in 7 and 3.3% of patients who were symptomatic and asymptomatic,
respectively. There were statistically significant differences between
symptomatic and asymptomatic patients (P=0.02). Clinically significant
histopathologic findings were observed in 22 cases, and 12 of the 22 cases were
diagnosed as having Crohn's disease. CONCLUSION: Terminal ileum intubation is
particularly indicated in symptomatic patients. In cases of chronic diarrhea,
iron-deficiency anemia, abdominal pain, and suspected inflammatory bowel disease,
terminal ileum intubation should be done.
PMID- 29334519
TI - The Most Common Causes of Eye Pain at 2 Tertiary Ophthalmology and Neurology
Clinics.
AB - BACKGROUND: Eye pain is a common complaint, but no previous studies have
determined the most common causes of this presenting symptom. Our objective was
to determine the most common causes of eye pain in 2 ophthalmology and neurology
departments at academic medical centers. METHODS: This was a retrospective cross
sectional analysis and chart review at the departments of ophthalmology and
neurology at the University Hospital Zurich (USZ), University of Zurich,
Switzerland, and the University of Utah (UU), USA. Data were analyzed from
January 2012 to December 2013. We included patients aged 18 years or older
presenting with eye pain as a major complaint. RESULTS: Two thousand six hundred
three patient charts met inclusion criteria; 742 were included from USZ and 1,861
were included from UU. Of these, 2,407 had been seen in an ophthalmology clinic
and 196 had been seen in a neurology clinic. Inflammatory eye disease
(conjunctivitis, blepharitis, keratitis, uveitis, dry eye, chalazion, and
scleritis) was the underlying cause of eye pain in 1,801 (69.1%) of all patients
analyzed. Although only 71 (3%) of 2,407 patients had migraine diagnosed in an
ophthalmology clinic as the cause of eye pain, migraine was the predominant cause
of eye pain in the neurology clinics (100/196; 51%). Other causes of eye pain in
the neurology clinics included optic neuritis (44 patients), trigeminal
neuralgia, and other cranial nerve disorders (8 patients). CONCLUSIONS: Eye pain
may be associated with a number of different causes, some benign and others sight
or life-threatening. Because patients with eye pain may present to either a
neurology or an ophthalmology clinic and because the causes of eye pain may be
primarily ophthalmic or neurologic, the diagnosis and management of these
patients often requires collaboration and consultation between the 2 specialties.
PMID- 29334520
TI - Invited Commentary: Evaluation of Horner Syndrome in the MRI Era.
AB - : This Invited Commentary discusses the following article: BACKGROUND:: To
identify the etiologies of adult Horner syndrome (HS) in the MRI era using a
targeted evaluation approach and to assess the value and yield of targeted
imaging. METHODS: A retrospective chart review was performed of 200 adult
outpatients with HS, confirmed with cocaine eyedrop testing. Patients were
divided into subgroups based on the presence or absence of symptoms and those who
did or did not receive additional testing with hydroxyamphetamine drops. Imaging
was obtained based on pharmacologic localization and/or clinical evaluation. The
etiology of HS and the yield of imaging were determined in all subgroups.
RESULTS: Imaging showed causative lesions in 24 of 179 (12.84%) imaged patients
with HS, and 13 (69.0%) were determined "idiopathic." Of the patients who
underwent testing with hydroxyamphetamine drops (132 patients), 86 had a
postganglionic localization with an imaging yield of 8.1%, and 46 had
preganglionic cause with an imaging yield of 21.7%. Fifty-three patients (26.5%)
never noticed ptosis/anisocoria before examination, and the imaging yield in this
subgroup was 2.8%. Eighteen of the 200 patients (9.0%) had serious pathology,
including carotid artery dissection, brain, or neck mass, and 6 of these (31.6%)
had acute symptoms and/or pain. CONCLUSION: HS is most often idiopathic with
serious pathology being relatively infrequent. When determining etiology, the
absence of symptoms is not predictive of the pathology. However, acute onset of
symptoms and/or pain are possible indicators for serious pathology. Localizing
the lesion using hydroxyamphetamine drops whenever obtainable and available is
still an efficient way to target imaging evaluation.
PMID- 29334521
TI - New Educational Model to Promote Breast Cancer-Preventive Behaviors (ASSISTS):
Development and First Evaluation.
AB - BACKGROUND: The prevalence of breast cancer in Iran has increased. An effective
approach to decrease the burden of breast cancer is prevention. OBJECTIVE: The
aim of this study was to develop and evaluate an educational model, called the
ASSISTS, for promoting breast cancer-preventive behaviors in women. METHODS: A
multiphase method was used to develop the model designed to promote breast cancer
prevention behaviors. A conceptual model was generated based on a secondary
analysis of qualitative data. Then, a structural equation model technique was
used to test the relationships among the model constructs. RESULTS: The analysis
revealed that 7 constructs could be extracted, namely, perceived social support,
attitude, motivation, self-efficacy, information seeking, stress management, and
self-care. Based on these constructs, a conceptual model was built and tested
using structural equation modeling. The model fit was good, and the model
confirmed significant relationships among the 7 constructs of breast cancer
prevention. CONCLUSION: Findings revealed that self-care behavior and stress
management are influenced directly by attitude, motivation, self-efficacy,
information seeking, and social support. In addition, women seek more information
when they are motivated, have more self-efficacy, have a more positive attitude
toward breast cancer prevention, and experience more social support. IMPLICATION
FOR PRACTICE: Cancer nurses can be at the forefront of breast cancer prevention.
Because they can play a pivotal role in providing information, they can reduce
women's stress and increase their self-care behavior. In addition, their social
support can positively influence Iranian women's attitude, motivation, and self
care behavior. Furthermore, implementing educational programs based on this model
might encourage women to practice preventive behaviors.
PMID- 29334522
TI - Themes in Literature Related to Incidence, Risk, and Prevention of Cancer in
Solid-Organ Transplantation Recipients on Immunosuppressive Therapy.
AB - BACKGROUND: Solid-organ transplants provide a second chance to thousands of
critically ill patients with end-organ failure each year. Immunosuppressants are
administered to patients to prevent graft rejection of a transplanted organ, such
as a heart, kidney, or liver, while placing the recipient at greater risk for
infection and cancer. OBJECTIVE: The literature provides evidence of various
cancers that have been found to develop in patients' posttransplantation. The
purpose of this comprehensive review is to investigate the incidence, risk, and
prevention of cancer in solid-organ transplantation recipients on
immunosuppressive therapy. METHODS: Google Scholar, Cumulative Index to Nursing
and Allied Health Literature and Ovid databases were searched to identify
research articles in peer-reviewed journals from 2011 to 2016. Variables under
examination included cancer risk, cancer type, incidence, demographic
characteristics, prevention, screening modalities, and education tools. RESULTS:
Six articles met the inclusion criteria. Results indicate that malignancy is a
prominent postoperative finding in at least 4% to 5% of solid-organ transplant
recipients, with evidence of various cancer types. Risk factors include male sex,
increased age, number of years posttransplant, fair skin, white race, and UV
exposure. Screening intervals and educational tools have been found to increase
awareness and target those at greater risk. CONCLUSION: Skin cancer and non
Hodgkin lymphoma were the most commonly diagnosed cancers in transplant
recipients. IMPLICATIONS FOR PRACTICE: Practitioners may find utility in
screening tools, self-examination education for patients, and follow-up protocols
to prevent further complications in this patient population. Early detection of
cancer and those at risk may help decrease morbidity and mortality rates in organ
recipients.
PMID- 29334523
TI - Not a Straight Line-Patients' Experiences of Prostate Cancer and Their Journey
Through the Healthcare System.
AB - BACKGROUND: Cancer and its treatment can severely impact quality of life, giving
rise to complex needs with respect to follow-up care. To support patient needs
and increase efficiency of care with limited resources, the Swedish government
has launched national reforms to redesign cancer care pathways. OBJECTIVE: The
aim of this study was to explore how prostate cancer patients experience their
journey through the healthcare system when their care is provided according to
the standardized care pathway, as described in healthcare policy documents.
METHODS: A qualitative, descriptive approach with individual interviews was used.
A template of a standardized prostate cancer pathway, created together with
healthcare professionals, was used during interviews. Fourteen interviews were
conducted with prostate cancer patients all operated on at a midsized hospital in
southeast Sweden between October 2015 and April 2016. The interviews were
analyzed with qualitative content analysis and illustrated in a patient journey
map. RESULTS: We identified an overall theme, "walking a tightrope," consisting
of 4 categories: "waiting," "becoming familiar with a troublesome body,"
"adjusting to a different life," and "information challenges." CONCLUSIONS: The
clinical implementation of the standardized care pathway is described as a
straight path through care, but patients described their experiences as walking a
tightrope. Lack of information, especially about cancer treatment and its adverse
effects, was the most common experience. IMPLICATIONS FOR PRACTICE: Our findings
indicate areas where further healthcare tools could improve patient experiences
of cancer treatment. This could include offering individualized information and
tools to increase patient empowerment, as well as patient/caregiver collaboration
(co-care).
PMID- 29334524
TI - Leveraging Linkage of Cohort Studies With Administrative Claims Data to Identify
Individuals With Cancer.
AB - BACKGROUND: In an effort to overcome quality and cost constraints inherent in
population-based research, diverse data sources are increasingly being combined.
In this paper, we describe the performance of a Medicare claims-based incident
cancer identification algorithm in comparison with observational cohort data from
the Nurses' Health Study (NHS). METHODS: NHS-Medicare linked participants' claims
data were analyzed using 4 versions of a cancer identification algorithm across 3
cancer sites (breast, colorectal, and lung). The algorithms evaluated included an
update of the original Setoguchi algorithm, and 3 other versions that differed in
the data used for prevalent cancer exclusions. RESULTS: The algorithm that
yielded the highest positive predictive value (PPV) (0.52-0.82) and kappa
statistic (0.62-0.87) in identifying incident cancer cases utilized both Medicare
claims and observational cohort data (NHS) to remove prevalent cases. The
algorithm that only used NHS data to inform the removal of prevalent cancer cases
performed nearly equivalently in statistical performance (PPV, 0.50-0.79; kappa,
0.61-0.85), whereas the version that used only claims to inform the removal of
prevalent cancer cases performed substantially worse (PPV, 0.42-0.60; kappa, 0.54
0.70), in comparison with the dual data source-informed algorithm. CONCLUSIONS:
Our findings suggest claims-based algorithms identify incident cancer with
variable reliability when measured against an observational cohort study
reference standard. Self-reported baseline information available in cohort
studies is more effective in removing prevalent cancer cases than are claims data
algorithms. Use of claims-based algorithms should be tailored to the research
question at hand and the nature of available observational cohort data.
PMID- 29334525
TI - Temporal Patterns of Exposure to Asbestos and Risk of Asbestosis: An Analysis of
a Cohort of Asbestos Textile Workers.
AB - OBJECTIVE: The aim of the study was to assess the risk of asbestosis death based
on the temporal pattern of exposure to asbestos. METHODS: We followed up a cohort
of asbestos textile workers, employed in 1946 to 1984, until November 2013. We
measured the duration of the employment, the time since last employment (TSLE),
the age, and the year of first employment. Hazard ratios (HR) were estimated
through multivariable Cox regression models. RESULTS: We observed 51 asbestosis
deaths among 1823 workers. The HR of asbestosis death increased with exposure
duration (HR 2.4 for >=15 years compared with <5 years, P trend = 0.014) and
declined with TSLE (HR 0.3 for >=25 compared with <5 years, P = 0.004). The risk
of asbestosis mortality strongly declined for exposure starting after 1968.
CONCLUSIONS: The risk of asbestosis death strongly declines in the decades after
cessation of the exposure.
PMID- 29334526
TI - Airborne Particulate Matter: Human Exposure and Health Effects.
AB - OBJECTIVE: Exposure to airborne particulate matter (PM) is estimated to cause
millions of premature deaths annually. This work conveys known routes of exposure
to PM and resultant health effects. METHODS: A review of available literature.
RESULTS: Estimates for daily PM exposure are provided. Known mechanisms by which
insoluble particles are transported and removed from the body are discussed.
Biological effects of PM, including immune response, cytotoxicity, and
mutagenicity, are reported. Epidemiological studies that outline the systemic
health effects of PM are presented. CONCLUSION: While the integrated, per capita,
exposure of PM for a large fraction of the first-world may be less than 1 mg per
day, links between several syndromes, including attention deficit hyperactivity
disorder (ADHD), autism, loss of cognitive function, anxiety, asthma, chronic
obstructive pulmonary disease (COPD), hypertension, stroke, and PM exposure have
been suggested. This article reviews and summarizes such links reported in the
literature.
PMID- 29334527
TI - Transanal Minimally Invasive Anal Canal Polyp Resection.
AB - Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are
operative endoscopies that have been performed since a long time. Recently, an
evolution of laparoscopy called transanal minimally invasive surgery began to be
popularized, and it can be adopted in the face of difficult cases for EMR/ESD. In
this video, a 36-year-old woman was submitted to transanal minimally invasive
surgery resection, after unsuccessful ESD, for a 2-cm polyp located anteriorly in
the anal canal, just beyond the pectineal line. Preoperative workup showed a uT1m
versus T1sm N0 M0 lesion. The procedure was performed with a new reusable
transanal platform and a monocurved coagulating hook and grasping forceps. The
operative time was 90 minutes. No perioperative complications were registered,
and the patient was discharged on postoperative day 1. The pathologic report
showed a villotubular adenoma with high-grade dysplasia and distant-free margins.
After 1 year, the patient was going well, without any recurrent disease.
Transanal minimally invasive surgery resection is a good alternative to
conventional endoscopic therapies, allowing a meticulous dissection under the
magnified operative field's exposure, and a mucosal-submucosal flap closure under
satisfactory surgeon's ergonomics.
PMID- 29334529
TI - Midterm Outcome of Kidney Transplantation From Donors With Thin Basement Membrane
Nephropathy.
AB - BACKGROUND: Thin basement membrane nephropathy (TBMN) is the most common cause of
persistent glomerular hematuria. Most individuals with TBMN show a benign course,
although it can be difficult to distinguish it from early stages of progressive
renal diseases. However, only limited studies address the prognosis of donors
with TBMN and their recipients. METHODS: From 2007 to 2016, 11 recipients
received kidney grafts from donors with TBMN, and their clinical data were
analyzed retrospectively. Follow-up protocol kidney biopsies were given to the
recipients at 10 days and 1 year after transplantation. The donors were also
received a follow-up evaluation of their renal function and were interviewed via
telephone survey. RESULTS: All donors were living, and their kidney grafts showed
TBMN on pretransplantation biopsy. The recipients were followed for 57.4 +/- 28.6
months posttransplantation. Seven recipients showed acute rejection by a median
of 9.7 months, and all recipients recovered their renal function after treatment.
Although 1 kidney failed due to graft arterial occlusion, the functions of the
others were preserved during the follow-up period. The donors were followed for
41.0 +/- 39.1 months and additionally contacted via telephone survey (in total,
56.8 +/- 32.0 months). All the donors maintained their renal function upon
clinical follow-up without significant complications and denied any discomfort at
the time of the telephone interview. CONCLUSIONS: Kidney transplant donors with
TBMN and their recipients maintained their renal function through midterm follow
up without significant complications. Therefore, kidney transplantation from
donors with TBMN could be a safe option.
PMID- 29334528
TI - Comparison of Laparoscopic and Open Pancreaticoduodenectomy for the Treatment of
Nonpancreatic Periampullary Adenocarcinomas.
AB - BACKGROUND: Laparoscopic pancreaticoduodenectomy (LPD), a surgical option for
nonpancreatic periampullary adenocarcinoma (NPPA), is a complex procedure that
has become increasing popular. However, there is no consensus as to whether this
technique should be performed routinely. Our aim was to evaluate the outcomes of
LPD compared with open pancreaticoduodenectomy (OPD). MATERIALS AND METHODS: From
October 2010 to September 2015, 58 LPDs were performed to treat NPPA and were
compared with 58 OPDs, which can theoretically be carried out by laparoscopic
approach. Patients were also matched based on their demographic data and
pathologic diagnosis. Demographic information, intraoperative and postoperative
data, pathologic data, and follow-up evaluation data were collected at our
center. RESULTS: All patients had a median follow-up of 34 months (range, 8 to 60
mo). Overall median survival during the study between the groups was not
different (P=0.760). No significant differences between the 2 groups were found
in terms of patient demographics, short-term complications, pathologic outcomes,
or tumor-node-metastasis stage. With regard to operative time, the LPD group was
slightly longer than the OPD group (P<0.001). There were significant differences
between groups in the time to the first passage of flatus and the time to oral
intake (P<0.001). However, no differences were seen in blood loss, length of
intensive care unit stay, node positive, or R0 resection between the laparoscopic
and open groups. CONCLUSIONS: This study found that LPD is a feasible, safe, and
effective method for the treatment of NPPA compared with OPD and may be a
preferred method for surgeons to choose.
PMID- 29334530
TI - Antegrade Arterial and Portal Flushing Versus Portal Flushing Only for Right Lobe
Live Donor Liver Transplantation-A Randomized Control Trial.
AB - BACKGROUND: In live donor liver transplantation portal flush only of the graft is
done on the bench. There are no data on antegrade arterial flush along with
portal flush of the graft. METHODS: Consecutive patients undergoing elective
right lobe live donor liver transplantation were block-randomized to receive
either portal flush only or both portal and antegrade arterial flush. The primary
objectives were safety, rate of early allograft dysfunction (EAD), and impact on
vascular and biliary complications. RESULTS: After randomization, there were 40
patients in each group. Both groups had comparable preoperative, intraoperative,
and donor variables. There were no adverse events related to arterial flushing.
The portal and antegrade arterial flush group had significantly lower
postoperative bilirubin on days 7, 14, and 21 (all P < 0.05), EAD (P = 0.005),
intensive care unit/high dependency unit (P = 0.01), and hospital stay (P =
0.05). This group also had lower peak aspartate aminotransferase (P = 0.07),
alanine aminotransferase (P = 0.06) and lower rates of sepsis (P = 0.08) trending
toward statistical significance. Portal and antegrade arterial flush groups had
lower ascitic fluid drainage and in-hospital mortality. Arterial and biliary
complications were not statistically different in the 2 groups. Multivariate
analysis of EAD showed portal with antegrade arterial flush was associated with
lower rate (P = 0.007), whereas model for end-stage liver disease Na (P = 0.01)
and donor age (P = 0.03) were associated with a higher rate of EAD. CONCLUSIONS:
Portal with antegrade arterial flushing of right lobe live liver grafts is safe,
significantly decreases postoperative cholestasis, EAD, intensive care unit/high
dependency unit, and hospital stay and is associated with lower rates of sepsis,
ascitic drainage and inhospital mortality in comparison to portal flush only.
PMID- 29334531
TI - Dangerously numb: opioids, benzodiazepines, chronic pain, and posttraumatic
stress disorder.
PMID- 29334532
TI - Cost-effectiveness and Improved Parent and Provider Satisfaction With Outpatient
Management of Pediatric Oncology Patients, With Low-risk Fever and Neutropenia.
AB - On the basis of significant evidence for safety, the international pediatric
fever and neutropenia committee recommends the identification and management of
patients with "low-risk fever and neutropenia" (LRFN), outpatient with oral
antibiotics, instead of traditional inpatient management. The aim of our study
was to compare the cost-per-patient with these 2 strategies, and to evaluate
parent and provider satisfaction with the outpatient management of LRFN. Between
March 2016 and February 2017, 17 LRFN patients (median absolute neutrophil count,
90/MUL) were managed at a single institution, per new guidelines. Fifteen
patients were discharged on presentation or at 24 to 48 hours postadmission on
oral levofloxacin, and 2 were inadvertently admitted off protocol. The mean cost
of management for the postimplementation cohort was compared with a historic
preimplementation control group. Satisfaction surveys were completed by parents
and health care providers of LRFN patients. The mean total cost of an LRFN
episode was $12,500 per patient preimplementation and $6168 postimplementation, a
decrease of $6332 (51%) per patient. All parents surveyed found outpatient follow
up easy; most (12/14) parents and all (16/16) providers preferred outpatient
management. Outpatient management of LRFN patients was less costly, and was
preferred by a majority of parents and all health care providers, compared with
traditional inpatient management.
PMID- 29334533
TI - The Moonshot Initiative: Randomized, Controlled Trials, and Its Impact in
Pediatric Oncology.
PMID- 29334534
TI - Symptomatic Hyperammonemia With Erwinia chrysanthemi-derived Asparaginase in
Pediatric Leukemia Patients.
AB - Erwinia chrysanthemi-derived asparaginase is increasingly integral to acute
lymphoblastic leukemia therapy. In our series, 16% of patients developed
symptomatic hyperammonemia following Erwinia administration with symptoms
including refractory nausea, vomiting, profound fatigue, malaise, and coma. This
series of patients receiving Erwinia indicates higher than expected incidence of
hyperammonemia, correlation between ammonia and asparaginase levels and
therapeutic asparaginase activity levels despite dose reduction. The series
provides evidence for investigation into which patients require intervention to
prevent toxicity, which patients may have ammonia levels used as an asparaginase
activity surrogate and which patients may achieve equivalent efficacy with
abridged dosing.
PMID- 29334535
TI - Simultaneous Presentation of Wilms' Tumor and Contralateral Ganglioneuroma in a
Child: Case Report and Literature Review.
AB - We demonstrate a 4-year-old girl who presented with progressive, asymmetrical,
firm abdominal distention and was diagnosed with synchronous Wilms' tumor and
left para-aortic ganglioneuroma (GN). Although synchronous tumors in the
pediatric population are commonly associated with malignancy-predisposing
syndromes, the patient in question was found to be otherwise healthy and had no
clinical evidence nor family history of a syndrome. This case is the second one
in the literature diagnosed with synchronous presentation of Wilms' tumor and GN
in a previously healthy child. In addition, a GN foci presumed to be a previous
metastasis of a neurogenic tumor that subsequently matured to GN was depicted
within a left para-aortic lymph node. We aimed to emphasize an extremely rare
synchronous occurrence of these embryonal tumors, increase the awareness of
physicians, and discuss the radiologic differential diagnosis and management.
PMID- 29334536
TI - Nationwide Trend Analysis of Pediatric Inpatients With Immune Thrombocytopenia in
the United States.
AB - BACKGROUND: Several studies have reported the epidemiology of immune
thrombocytopenia (ITP) among children in the United States and other countries.
However, recent trends in ITP among hospitalized children and hospital course
remain unknown at a national level in the United States. METHOD: Hospital
discharge records of patients with ITP aged 19 years and younger were obtained
for the years 2003, 2006, 2009, and 2012 using the Kids' Inpatient Database. Data
were weighted to estimate the annual hospitalization rates in the United States
with trend analyses. Multivariable regression models were used to ascertain
trends of health care utilizations, hospitalization costs, and length of stay.
RESULTS: Total annual hospitalization rates due to ITP ranged from 6.13 per
100,000 children in 2003 to 6.22 per 100,000 children in 2012 (Ptrend=0.86). The
lowest proportions of hospitalizations were observed in August. The proportions
of inpatients treated with intravenous immunoglobulin increased from 18.5% in
2003 to 39.9% (Ptrend< 0.001), while those examined with bone marrow aspiration
decreased from 7.8% in 2003 to 6.5% in 2012 (Ptrend=0.01). Total hospitalization
costs and length of stay changed from $6147 and 3.78 days in 2003 to $9328 and
2.55 days in 2012. CONCLUSIONS: We provided insights of epidemiology of ITP and
health care utilizations in the United States. Further studies, including cost
effective analyses, will be required to justify the increasing trends in health
care costs and intravenous immunoglobulin.
PMID- 29334537
TI - Isolated Central Nervous System Chloroma as a Presenting Sign of Relapsed
Pediatric Acute Lymphoblastic Leukemia.
AB - Central nervous system (CNS) chloromas are an exceedingly rare presentation of
CNS relapse in acute lymphoblastic leukemia (ALL). We report a relapsed ALL
patient who presented with 2 separate chloromas and cerebrospinal fluid
lymphoblastocytosis, and outline a treatment plan of systemic chemotherapy and
CNS-directed radiation therapy. A review of the literature indicates that
multiagent chemotherapy combined with CNS radiotherapy is effective, with
hematopoietic stem cell transplantation used in half of reported cases. We
conclude that intensive systemic multiagent chemotherapy with CNS-directed
radiation therapy can be successfully used to treat relapsed pediatric ALL with
CNS lymphoblastic chloroma.
PMID- 29334538
TI - Sickle Cell Trait Testing Should Not Be a Player in NCAA Athletics: Examining the
Media's Role in Disseminating Awareness and Information.
PMID- 29334539
TI - Gelatin-Based Hemostatic Agents: Histopathologic Differences.
AB - PURPOSE: To delineate the histopathologic appearance of gelatin-based hemostatic
agents, Surgiflo, Gelfoam, and Floseal, which are used by ophthalmic plastic
surgeons, and which may incidentally be found as foreign materials in
histopathologic tissue samples. METHODS: Histopathologic analysis was performed
with hematoxylin-eosin, periodic acid-Schiff, Masson trichrome, and elastin
staining on tissue samples in which gelatin-based agents were found. To better
characterize these materials, similar analyses were performed on in vitro samples
of commonly used gelatin-based hemostatic agents. RESULTS: Surgiflo and Gelfoam
are composed of small stellate pieces of gelatin with a smooth, homogeneous
quality. In tissues, they are faintly positive with periodic acid-Schiff
staining, amphophilic with Masson trichrome staining, and ink-black with elastin
staining. Floseal has a distinctly different morphology of large rectangular
sheets, yet almost identical in vitro staining properties. DISCUSSION: While the
morphology of the gelatin-based hemostatic agents is consistent under various
conditions, the staining properties of these materials differ based on whether
they have been in contact with human tissue. CONCLUSIONS: Gelatin-derived
hemostatic agents are best identified based on their morphologic characteristics.
Elastin staining highlights these materials prominently within tissue samples and
may be helpful in distinguishing them from other foreign materials.
PMID- 29334540
TI - Predictors of Success Following Muller's Muscle-Conjunctival Resection.
AB - PURPOSE: This study aims to describe Muller's muscle-conjunctival resection
surgery in terms of outcomes and potential factors that may predict final
positions. METHODS: This cross-sectional cohort study included patients
undergoing Muller's muscle-conjunctival resection surgery for involutional ptosis
over a 15-year period. Success was defined in 2 ways: 1) final marginal reflex
distance 1 (MRD1) >=2.5 mm (MRD1 success) and 2) final difference in MRD1 <=1 mm
between eyelids (symmetry success). Percentages of patients achieving both
outcomes were calculated. Predictors of outcome were assessed using bivariate
analysis and multivariate models. RESULTS: The final sample included 315 eyes in
192 patients. The mean age (standard deviation) was 67.9 (11.9) years, and 60.0%
were female. MRD1 >=2.5 mm was achieved in 65.7% of the sample. Symmetry within 1
mm was achieved in 82.9% of the sample. Significant (p < 0.05) predictors of MRD1
success were female sex, concurrent lower eyelid blepharoplasty, and higher
preoperative MRD1 in bivariate analysis; preoperative MRD1 and female sex in the
multivariate model; and preoperative MRD1 in the a priori model. Significant (p <
0.05) predictors of symmetry success were female sex, previous lower eyelid
blepharoplasty, concurrent lateral canthoplasty, preoperative symmetry, and older
age in bivariate analysis; only female sex in the multivariate model. DISCUSSION:
Muller's muscle-conjunctival resection is effective for elevating the eyelid in
ptosis and may be more effective for achieving symmetry than absolute elevation
over 2.5 mm. The results remain difficult to predict based clinical, surgical, or
demographic factors.
PMID- 29334541
TI - A Novel Technique for Measuring Eyelid Force.
AB - PURPOSE: We present a novel technique to directly measure the eyelid upward force
generation. This technique can be used during routine clinical examination using
an inexpensive, portable force gauge. METHODS: This prospective case series was
conducted January to June 2015 in an ophthalmology clinic affiliated with a
tertiary care medical center. A convenience sample of 42 patients (40-90 years of
age) without known eyelid pathology participated. The eyelid upward net force
generated was measured directly using a handheld dynamometer noninvasively
attached to the upper eyelid. Comparison of the eyelid-brow upward force
generated with eyelid upward net force generated allowed us to assess the
contribution of levator and frontalis muscles to the force generated during
upgaze. Data were evaluated with relation to gender and age. RESULTS: Upper
eyelid force generated was 53.3 g OD and 53.9 g OS; the generated force during
frontalis muscle fixation was 38.4 g OD and 41.1 g OS. The levator and frontalis
muscles showed a 3:1 ratio respectively in their contribution to the force
generated during upgaze. Although no statistically significant differences were
seen between eyes, gender, or within age groups, younger patients showed
increased generating force which is attributed to the levator muscle. Interclass
correlation coefficient showed virtually no correlation between clinical eyelid
assessments and direct muscle force measurement. Reliability for repeated direct
force measurements by the same physician was strong, with interclass correlation
coefficient 0.951 to 0.969. No adverse events occurred. CONCLUSIONS: We describe
a simple, reliable, inexpensive, new method for assessing upper eyelid upward
force generation. Because the levator muscle serves as the primary contributor to
eyelid elevation, this directly measurable eyelid assessment may help to increase
understanding of its functional contribution and assessment when assessing eyelid
pathologies.
PMID- 29334542
TI - Medial Buttressing in Orbital Blowout Fractures.
AB - PURPOSE: To study whether ethmoidectomy predisposes the orbit to medial wall
fracture with lesser trauma. METHODS: An interventional cadaver study of 5 heads
(10 orbits); the left or right orbit was randomized to undergo endoscopic
complete ethmoidectomy with the fellow orbit as control. Fractures were induced
with direct globe trauma, and heads underwent CT scanning. Energy to induce
fracture, peak orbital pressure at time of fracture, fracture pattern, and volume
of herniated tissue were measured and analyzed. RESULTS: Fractures were induced
in both orbits of all cadavers. Experimental orbits after ethmoidectomy sustained
orbital fracture at less energy required (2.14 +/- 0.66 vs. 3.10 +/- 0.19 J, mean
difference: -0.96 +/- 0.33 J, p < 0.05). Similarly, peak orbital pressure was
lower for ethmoidectomized orbits than for controls (11.8 +/- 8.42 vs. 28.4 +/-
13.2 mm Hg, mean difference: -16.5 +/- 6.9 mm Hg, p < 0.05). Orbits after
ethmoidectomy were more likely to sustain medial wall involvement in fracture
(100%) compared with controls (20%, p < 0.05) and pure medial wall fracture (80%)
compared with controls (0%, p < 0.05). Overall volume of herniated orbital
contents was not significantly different between groups (p = 0.25); volume of
herniated tissue from the medial wall only was significantly greater in orbits
after ethmoidectomy (mean difference: 1.01 +/- -0.39 cm, p < 0.05). CONCLUSION:
Endoscopic ethmoidectomy in fresh cadavers reduces impact energy necessary to
induce orbital fracture and increases the prevalence of medial wall involvement.
Clinicians may wish to counsel patients undergoing endoscopic sinus surgery about
these relative risks.
PMID- 29334543
TI - Seminoma Metastatic to the Orbit.
AB - PURPOSE: Seminomas are solid tumors in young men, but which rarely metastasize to
the orbit. The authors review the known literature on seminoma metastatic to the
orbit, and describe an additional case in a 33-year-old man. METHODS: A
literature search was performed on the MEDLINE database using keywords
"seminoma," "testicular germ-cell tumors," "testicular cancer," "testicular
neoplasm," "orbital metastasis," and "germ-cell neoplasms." RESULTS: Malignant
neoplasms of the testis account for only 1% of cancers in men. None-the-less,
testicular germ cell seminoma is the most common solid tumor found in young men
between the ages of 15 and 39. Only seven previous cases have been mentioned in
the literature. The pathogenesis remains unclear although genetic, environmental,
and maternal factors may play a role. The number of cases is too few to determine
the best treatment options, but surgical excision and adjunctive orbital
radiotherapy appear to be most appropriate. CONCLUSIONS: Although metastases to
the orbit are rare, seminoma should be considered in the differential diagnosis
of all young men with proptosis.
PMID- 29334544
TI - Blood biomarkers of expressed and inducible HIV-1.
AB - OBJECTIVE: To define the relationships between molecular measures of viral
persistence in blood (i.e., plasma viremia, cellular HIV-1 DNA, and mRNA) and
expressed or inducible virus from resting CD4 T cells of individuals on
suppressive antiretroviral therapy. DESIGN: We compared molecular measurements of
HIV-1 in plasma and in uncultured peripheral blood mononuclear cells (PBMCs) to
the levels of virions produced by either unstimulated or phorbol myristate
acetate and ionomycin (PMA/iono)-stimulated PBMC or resting CD4 T cells from 21
donors on suppressive antiretroviral therapy. RESULTS: We found that unstimulated
virion release from cultured resting CD4 T cells was positively correlated with
the levels of plasma viremia in vivo (Spearman rho = 0.67, P = 0.0017). We also
found that levels of both cellular HIV-1 DNA and unspliced HIV-1 mRNA per million
uncultured PBMC were positively correlated with the levels of inducible virion
release from both PMA/iono-stimulated PBMC (total HIV-1 DNA: rho = 0.64, P =
0.0017; unspliced HIV-1 RNA: rho = 0.77, P < 0.001) and PMA/iono-stimulated
resting CD4 T cells (total HIV-1 DNA: rho = 0.75, P < 0.001; unspliced HIV-1 RNA:
rho = 0.75, P < 0.001). CONCLUSION: These results show for the first time that
there are strong associations between in-vivo measures of HIV-1 persistence and
ex-vivo measures of spontaneous and inducible virus production from cultured PBMC
and resting CD4 T cells. Findings from this study provide insight into the
biology of HIV-1 persistence and suggest methods to guide the evaluation of
clinical strategies to reduce the size of the viral reservoir.
PMID- 29334545
TI - Bacterial vaginosis modifies the association between hormonal contraception and
HIV acquisition.
AB - OBJECTIVE: To examine bacterial vaginosis as an effect modifier for the
association between hormonal contraception and incident HIV infection. DESIGN:
Serodiscordant couples enrolled in an open longitudinal cohort in Lusaka, Zambia
from 1994 to 2012. This analysis was restricted to couples with an HIV-positive
man enrolled between1994 and 2002 when a quarterly genital tract examination and
HIV testing was performed. METHODS: Multivariate Cox models evaluated the
association between contraceptive method and HIV-acquisition, stratified by time
varying bacterial vaginosis status. RESULTS: Among 564 couples contributing
1137.2 couple-years of observation, bacterial vaginosis was detected at 15.5% of
study visits. Twenty-two of 106 seroconversions occurred during intervals after
bacterial vaginosis was detected [12 on no method/nonhormonal method (nonhormonal
contraception), two on injectables, eight on oral contraceptive pills (OCPs)].
Unadjusted seroincidence rates per 100 couple-years for nonhormonal
contraception, injectable, and OCP users, respectively, during intervals with
bacterial vaginosis were 8.3, 20.8, and 31.0 and during intervals without
bacterial vaginosis were 8.2, 9.7, and 12.3. In the bacterial vaginosis-positive
model, there was a significant increase in incident HIV among those using
injectables (adjusted hazard ratio, aHR 6.55, 95% CI 1.14-37.77) and OCPs (aHR
5.20, 95% CI 1.68-16.06) compared with nonhormonal contraception. Hormonal
contraception did not increase the hazard of HIV acquisition in bacterial
vaginosis-negative models. These findings persisted in sensitivity analyses
whenever all covariates from the nonstratified model previously published were
included, whenever other genital tract findings were excluded from the model and
with the addition of condom-less sex and sperm on wet-prep. CONCLUSION: Future
research should consider a potential interaction with bacterial vaginosis
whenever evaluating the impact of hormonal contraception on HIV acquisition.
PMID- 29334546
TI - Impact of early antiretroviral therapy eligibility on HIV acquisition: household
level evidence from rural South Africa.
AB - OBJECTIVES: We investigate the effect of immediate antiretroviral therapy (ART)
eligibility on HIV incidence among HIV-uninfected household members. DESIGN:
Regression discontinuity study arising from a population-based cohort. METHODS:
Household members of patients seeking care at the Hlabisa HIV Treatment and Care
Programme in rural KwaZulu-Natal South Africa between January 2007 and August
2011 with CD4 cell counts up to 350 cells/MUl were eligible for inclusion if they
had at least two HIV tests and were HIV-uninfected at the time the index patient
linked to care (N = 4115). Regression discontinuity was used to assess the
intention-to-treat effect of immediate versus delayed ART eligibility on HIV
incidence among household members. Exploiting the CD4 cell count-based threshold
rule for ART initiation (CD4 < 200 cells/MUl until August 2011), we used Cox
proportional hazards models to compare outcomes for household members of patients
who presented for care with CD4 cell counts just above versus just below the ART
initiation threshold. RESULTS: Characteristics of household members of index
patients initiating HIV care were balanced between those with an index patient
immediately eligible for ART (N = 2489) versus delayed for ART (N = 1626). There
were 337 incident HIV infections among household members, corresponding to an HIV
incidence of 2.4 infections per 100 person-years (95% confidence interval 2.5
3.1). Immediate eligibility for treatment reduced HIV incidence in households by
47% in our optimal estimate (hazard ratio = 0.53, 95% confidence interval 0.30
0.96), and by 32-60% in alternate specifications of the model. CONCLUSION:
Immediate eligibility of ART led to substantial reductions in household-level HIV
incidence.
PMID- 29334547
TI - Quality of life improvement in resource-limited settings after one year of second
line antiretroviral therapy use among adult men and women.
AB - OBJECTIVE: We evaluated improvement of quality of life (QoL) after 1 year of
second-line antiretroviral therapy (ART) use in resource-limited settings (RLS)
among adult men and women, comparing two randomized treatment arms. DESIGN: The
AIDS Clinical Trial Group A5273 was a randomized clinical trial of second-line
ART comparing lopinavir/ritonavir (LPV/r) + raltegravir with LPV/r +
nucleos(t)ide reverse transcriptase inhibitors (NRTIs) in participants failing a
non-NRTI-containing regimen at 15 sites in nine RLS. Participants completed the
AIDS Clinical Trial Group short-form-21 which has eight QoL domains with a
standard score ranging from 0 (worst) to 100 (best). METHODS: Differences in QoL
by randomized arm, as well as by demographic and clinical variables, were
evaluated by regression models for baseline and week 48 QoL scores fitted using
the generalized estimating equations method. RESULTS: A total of 512 individuals
(49% men, median age 39 years) were included. A total of 512 and 492 participants
had QoL assessments at baseline and week 48, respectively. QoL improved
significantly from baseline to week 48 (P < 0.001 for all domains). There was no
significant difference between treatment arms for any domain. Individuals with
higher viral load and lower CD4 cell count at baseline had lower mean QoL at
baseline but larger improvements such that mean QoL was similar at week 48.
CONCLUSION: Improvements in QoL were similar after starting second-line ART of
LPV/r combined with either raltegravir or NRTIs in RLS. QoL scores at baseline
were lower among participants with worse disease status prior to starting second
line, but after 1 year similar QoL scores were achieved.
PMID- 29334548
TI - Plasma and intracellular pharmacokinetics of tenofovir in patients switched from
tenofovir disoproxil fumarate to tenofovir alafenamide.
AB - OBJECTIVES: The aim of the study was to compare the intraindividual plasma and
intracellular peripheral blood mononuclear cell (PBMC) pharmacokinetics of
tenofovir (TFV) and its intracellular metabolite, TFV-diphosphate (TFV-DP) in
patients switched from a fixed-dose combination (FDC) tablet of TFV disoproxil
fumarate (TDF)/emtricitabine (FTC)/elvitegravir (EVG)/cobicistat (COBI) to a FDC
containing TFV alafenamide (TAF)/FTC/EVG/COBI. DESIGN: A single-arm, prospective,
nonrandomized, cross-over, pharmacokinetic study in patients receiving a TDF
containing regimen (TDF 300 mg/FTC 200 mg/EVG 150 mg/COBI 150 mg) switched to a
TAF-containing FDC regimen (TAF 10 mg/FTC 200 mg/EVG 150 mg/COBI 150 mg).
METHODS: Single, sparse plasma and PBMC samples were collected during TDF therapy
and 4-8 weeks post-switch to the TAF-containing regimen. Plasma TFV and cell
associated TFV-DP concentrations were determined with validated liquid
chromatography tandem mass spectrometry methods. PBMC cell enumeration was
performed by quantification of RNaseP (RPP30) gene copy numbers using a highly
sensitive droplet digital PCR assay. Plasma and PBMC pharmacokinetics were
summarized as geometric mean and compared as a geometric mean ratio with a
Wilcoxon signed-rank test. RESULTS: In 30 participants with evaluable data, TFV
plasma concentrations decreased 90% [TDF: 99.98 (2.24) ng/ml vs. TAF: 10.2 (1.6)
ng/ml, P < 0.001] after the switch while cell-associated TFV-DP increased 2.41
fold [TAF: 834.7 (2.49) vs. TDF: 346.85 (3.75) fmol/10 cells, P = 0.004].
CONCLUSION: Intraindividually, plasma TFV concentrations significantly decreased
while cell associated TFV-DP concentrations significantly increased after
switching from a TDF to a TAF-containing antiretroviral therapy regimen.
PMID- 29334549
TI - Cost-effectiveness of alternative strategies for provision of HIV preexposure
prophylaxis for people who inject drugs.
AB - BACKGROUND: Oral HIV preexposure prophylaxis (PrEP) has been recommended as a
means of HIV prevention among people who inject drugs (PWIDs) but, at current
prices, is unlikely to be cost-effective for all PWID. OBJECTIVE: To determine
the cost-effectiveness of alternative strategies for enrolling PWID in PrEP.
DESIGN: Dynamic network model that captures HIV transmission and progression
among PWID in a representative US urban center. OUTCOME MEASURES: HIV infections
averted, discounted costs and quality-adjusted life-years (QALYs), and
incremental cost-effectiveness ratios. INTERVENTION: We assume 25% PrEP coverage
and investigate four strategies: first, random PWID are enrolled (Unselected
Enrollment); second, individuals are randomly selected and enrolled together with
their partners (Enroll Partners); third, individuals with the highest number of
sexual and needle-sharing partnerships are enrolled (Most Partners); fourth,
individuals with the greatest number of infected partners are enrolled (Most
Positive Partners). RESULTS: PrEP can achieve significant health benefits:
compared with the status quo of no PrEP, the strategies gain 1114 QALYs
(Unselected Enrollment), 2194 QALYs (Enroll Partners), 2481 QALYs (Most
Partners), and 3046 QALYs (Most Positive Partners) over 20 years in a population
of approximately 8500 people. The incremental cost-effectiveness ratio of each
strategy compared with the status quo (cost per QALY gained) is $272 000
(Unselected Enrollment), $158 000 (Enroll Partners), $124 000 (Most Partners),
and $101 000 (Most Positive Partners). All strategies except Unselected
Enrollment are cost-effective according to WHO criteria. CONCLUSION: Selection of
high-risk PWID for PrEP can improve the cost-effectiveness of PrEP for PWID.
PMID- 29334551
TI - Rapid decline of HIV-1 DNA and RNA in infants starting very early antiretroviral
therapy may pose a diagnostic challenge.
AB - OBJECTIVE: Birth diagnosis of HIV-1 infection offers an ideal opportunity for
early antiretroviral therapy (ART) to limit HIV-1 reservoir size and limit
disease progression. Although data on cellular HIV-1 DNA decay exist for children
commencing treatment from 2 to 3 months of age, data are lacking for starting
shortly after birth. DESIGN: We studied infants who initiated ART within 8 days
after birth to assess HIV-1 DNA levels longitudinally. METHODS: Children were
recruited from public health clinics in Cape Town where birth diagnosis of HIV-1
coupled with early ART initiation occurred. Total cellular HIV-1 DNA levels were
determined using a sensitive quantitative PCR targeting a conserved region in
integrase. RESULTS: Of 11 infants diagnosed and beginning ART within 8 days of
birth with detectable pre-ART HIV-1 DNA, three subsequently had undetectable HIV
1 DNA after 6 days, 3 months and 4 months on treatment, respectively. In seven
who had virologic suppression (defined as a continuous downward trend in plasma
HIV-1 RNA, and <100 copies/ml after 6 months) total HIV-1 DNA continued to decay
over 12 months [mean half-life of 64.8 days (95% confidence interval: 47.9
105.7)]. CONCLUSION: In infants initiated on ART within 8 days of life the
combination of maternal ART, and early ART for prophylaxis and treatment
contribute to rapid decline of HIV-1 infected cells to low or undetectable
levels. However, rapid decline of HIV-1 RNA and DNA may complicate definitive
diagnosis when confirmatory testing is delayed.
PMID- 29334553
TI - Post-treatment controllers after treatment interruption in chronically HIV
infected patients.
AB - OBJECTIVE: Control HIV replication requires continuous combined antiretroviral
therapy (cART) as discontinuation of cART results in a rapid viral rebound.
However, a few individuals exist who took cART for several years and did not show
the expected viral rebound after treatment cessation. Most post-treatment
controllers (PTCs) are early treated individuals. We report three cases who
started cART during chronic infection. DESIGN: Patients were treated and
monitored according to Italian guidelines. For the description of cases, the
percentage of CD8CD38HLA*DR cells, CD8CD38HLA*DR cells, major histocompatibility
complex genotyping, total HIV-DNA and plasma levels of anti-retroviral (ARV)
drugs were performed. RESULTS: Patients started therapy during chronic infection.
Patient 26636 started her first ARV drug two years after diagnosis and patients
93016 and 50293 started cART with high viral loads and low CD4 cell counts. Time
without cART was 13, 11 and 1.5 years, respectively. None presented any of the
protective class I HLA alleles and patient 93016 has the HLA-B*35 allele that
appears to be enriched in PTCs. Patients 93016 and 50293 had very low levels of
CD8CD38HLA*DR cells (<5%) much lower than those of patient 26636 (27%). T-cell
associated HIV-DNA was 3.78, 3.48 and 3.13 log copies/10 CD4, respectively.
CONCLUSION: Patients like ours may advance our understanding of the
characteristics for which individuals may be more likely to achieve ART-free
remissions. Furthermore, our patients are among the few so far described who
started cART during chronic infection extending the hope that a functional cure
is possible even in this setting.
PMID- 29334554
TI - The Systemic-Immune-Inflammation Index Independently Predicts Survival and
Recurrence in Resectable Pancreatic Cancer and its Prognostic Value Depends on
Bilirubin Levels: A Retrospective Multicenter Cohort Study.
AB - OBJECTIVE: Our aim was to determine the prognostic significance of the systemic
immune-inflammation index (SIII) in patients with resectable pancreatic cancer,
using cancer-specific survival as the primary outcome. BACKGROUND: Pancreatic
cancer is associated with a dysfunctional immune system and poor prognosis. We
examined the prognostic significance of the SIII in patients with resectable
pancreatic ductal adenocarcinoma (PDAC) and the effects of bilirubin on this
index. METHODS: We retrospectively assessed all pancreatic resections performed
between 2004 and 2015 at 4 tertiary referral centers to identify pathologically
confirmed PDAC patients. Baseline clinicopathologic characteristics, preoperative
laboratory values such as absolute neutrophil, lymphocyte, and platelet counts, C
reactive protein, albumin, bilirubin, and CA19-9 levels, and also follow-up
information, were collected. The associations of the calculated inflammatory
indices with outcome were both internally and externally validated. RESULTS: In
all, 590 patients with resectable PDAC were included. The discovery and
validation cohort included 170 and 420 patients, respectively. SIII >900 [hazard
ratio (HR) 2.32, 95% confidence interval (CI) 1.55-3.48], lymph node ratio (HR
3.75, 95% CI 2.08-6.76), and CA19.9 >200 kU/L (HR 1.62, 95% CI 1.07-2.46) were
identified as independent predictors of cancer-specific survival. Separate model
analysis confirmed that preoperative SIII contributed significantly to
prognostication. However, SIII appeared to lose its prognostic significance in
patients with bilirubin levels above 200 MUmol/L. CONCLUSIONS: SIII is an
independent predictor of cancer-specific survival and recurrence in patients with
resectable PDAC. SIII may lose its prognostic significance in patients with high
bilirubin levels. Properly designed prospective studies are needed to further
confirm this hypothesis.
PMID- 29334550
TI - Chronic hepatitis C virus infection and subsequent HIV viral load among women
with HIV initiating antiretroviral therapy.
AB - OBJECTIVES: One in four persons living with HIV is coinfected with hepatitis C
virus (HCV). Biological and behavioral mechanisms may increase HIV viral load
among coinfected persons. Therefore, we estimated the longitudinal effect of
chronic HCV on HIV suppression after ART initiation among women with HIV (WWH).
DESIGN: HIV RNA was measured every 6 months among 441 WWH in the Women's
Interagency HIV Study who initiated ART from 2000 to 2015. METHODS: Log-binomial
regression models were used to compare the proportion of study visits with
detectable HIV RNA between women with and without chronic HCV. Robust sandwich
variance estimators accounted for within-person correlation induced by repeated
HIV RNA measurements during follow-up. We controlled for confounding and
selection bias (because of loss to follow-up and death) using inverse probability
of-exposure-and-censoring weights. RESULTS: One hundred and fourteen women (25%)
had chronic HCV before ART initiation. Overall, the proportion of visits with
detectable HIV RNA was similar among women with and without chronic HCV [relative
risk (RR) 1.19 (95% CI 0.72, 1.95)]. Six months after ART initiation, the
proportion of visits with detectable HIV RNA among women with chronic HCV was
1.88 (95% CI 1.41-2.51) times that among women without HCV, at 2 years, the ratio
was 1.60 (95% CI 1.17-2.19), and by 6 years there was no difference (1.03; 95% CI
0.60-1.79). CONCLUSION: Chronic HCV may negatively impact early HIV viral
response to ART. These findings reaffirm the need to test persons with HIV for
HCV infection, and increase engagement in HIV care and access to HCV treatment
among persons with HIV/HCV coinfection.
PMID- 29334555
TI - Multi-institutional Analysis of Recurrence and Survival After Neoadjuvant
Chemoradiotherapy of Esophageal Cancer: Impact of Histology on Recurrence
Patterns and Outcomes.
AB - OBJECTIVE: To determine the impact of histology on pathologic response, survival
outcomes, and recurrence patterns in patients with esophageal cancer (EC) who
received neoadjuvant chemoradiotherapy (CRT). SUMMARY OF BACKGROUND DATA: There
is a paucity of data regarding comparative outcomes after neoadjuvant CRT between
esophageal squamous cell carcinoma (SCC) and adenocarcinoma. METHODS: Between
2002 and 2015, 895 EC patients who underwent neoadjuvant CRT followed by
esophagectomy at 3 academic institutions were retrospectively reviewed, including
207 patients with SCC (23.1%) and 688 patients with adenocarcinoma (76.9%).
Pathologic response, survival, recurrence pattern, and potential prognostic
factors were compared. RESULTS: Pathologic complete response (pCR) rate was
significantly higher for SCC compared with adenocarcinoma (44.9% vs 25.9%, P <
0.001). After a median follow-up of 52.9 months, 71 patients (34.3%) with SCC
versus 297 patients (43.2%) with adenocarcinoma had recurrent disease (P =
0.023). For patients who achieved a pCR, no significant differences were found in
recurrence pattern, sites, or survival end-points between the 2 histology groups.
For non-pCR patients, the SCC group demonstrated significantly higher regional
and supraclavicular recurrence rates but a lower hematogenous metastasis rate
than adenocarcinoma patients, whereas the adenocarcinoma patients had a more
favorable locoregional failure-free survival (P = 0.005) and worse distant
metastasis-free survival (P = 0.024). No differences were found in overall
survival (P = 0.772) or recurrence-free survival (P = 0.696) between groups.
CONCLUSIONS: SCC was associated with a significantly higher pCR rate than
adenocarcinoma. Recurrence pattern and survival outcomes were significantly
different between the 2 histology subtypes in non-pCR patients.
PMID- 29334556
TI - Decoding Grade B Pancreatic Fistula: A Clinical and Economical Analysis and
Subclassification Proposal.
AB - OBJECTIVE: The aim of this study was to describe characteristics and management
approaches for grade B pancreatic fistula (B-POPF) and investigate whether it
segregates into distinct subclasses. BACKGROUND: The 2016 ISGPS refined
definition of B-POPF is predicated on various postoperative management
approaches, ranging from prolonged drainage to interventional procedures, but the
spectrum of clinical severity within this entity is yet undefined. METHODS:
Pancreatectomies performed at 2 institutions from 2007 to 2016 were reviewed to
identify B-POPFs and their treatment strategies. Subclassification of B-POPFs
into 3 classes was modeled after the Fistula Accordion Severity Grading System
(B1: prolonged drainage only; B2: pharmacologic management; B3: interventional
procedures). Clinical and economic outcomes, unique from the ISGPS definition
qualifiers, were analyzed across subclasses. RESULTS: B-POPF developed in 320 of
1949 patients (16.4%), and commonly required antibiotics (70.3%), prolonged
drainage (67.8%), and enteral/parenteral nutrition (54.7%). Percutaneous drainage
occurred in 79 patients (24.7%), always in combination with other strategies.
Management of B-POPFs was widely heterogeneous with a median of 2
approaches/patient (range 1 to 6) and 38 various strategy combinations used.
Subclasses B1-3 comprised 19.1%, 52.2%, and 28.8% of B-POPFs, respectively, and
were associated with progressively worse clinical and economic outcomes. These
results were confirmed by multivariable analysis adjusted for clinical and
operative factors. Notably, distribution of the B-POPF subclasses was influenced
by institution and type of resection (P < 0.001), while clinical/demographic
predictors proved elusive. CONCLUSION: B-POPF is a heterogeneous entity, where 3
distinct subclasses with increasing clinical and economic burden can be
identified. This classification framework has potential implications for accurate
reporting, comparative research, and performance evaluation.
PMID- 29334557
TI - So What's the Chance of This Mesh Causing Me a Problem in the Long Run?
PMID- 29334558
TI - Comment on: A Propensity Score Matched Analysis of Open Versus Minimally Invasive
Transthoracic Esophagectomy in the Netherlands.
PMID- 29334559
TI - Sex Differences in Faculty Rank Among Academic Surgeons in the United States in
2014.
AB - OBJECTIVE: The aim of this study was to evaluate sex differences in full
professorship among a comprehensive, contemporary cohort of US academic surgeons.
SUMMARY OF BACKGROUND DATA: Previous work demonstrates that women are less likely
than men to be full professors in academic medicine, and in certain surgical
subspecialties. Whether sex differences in academic rank exist across all
surgical fields, and after adjustment for confounders, is not known. METHODS: A
comprehensive list of surgeons with faculty appointments at US medical schools in
2014 was obtained from Association of American Medical Colleges (AAMC) faculty
roster and linked to a comprehensive physician database from Doximity, an online
physician networking website, which contained the following data for all
physicians: sex, age, years since residency, publication number (total and
first/last author), clinical trials participation, National Institutes of Health
grants, and surgical subspecialty. A 20% sample of 2013 Medicare payments for
care was added to this dataset. Multivariable regression models were used to
estimate sex differences in full professorship, adjusting for these variables and
medical school-specific fixed effects. RESULTS: Among 11,549 surgeon faculty at
US medical schools in 2014, 1692 (14.7%) were women. Women comprised 19.4% of
assistant professors (1072/5538), 13.8% of associate professors (404/2931), and
7.0% of full professors (216/3080). After multivariable analysis, women were less
likely to be full professors than men (adjusted odds ratio: 0.76, 95% confidence
interval: 0.6-0.9). CONCLUSION: Among surgical faculty at US medical schools in
2014, women were less likely than men to be full professors after adjustment for
multiple factors known to impact faculty rank.
PMID- 29334560
TI - Proposed Modification of the 8th Edition of the AJCC Staging System for
Pancreatic Ductal Adenocarcinoma.
AB - OBJECTIVE: The aim of this study was to improve the 8th edition (8th) of the
American Joint Committee on Cancer (AJCC) staging system for pancreatic ductal
adenocarcinoma (PDAC). BACKGROUND: The new 8th AJCC staging system for PDAC was
released in October, 2016, and will be applied in clinical practice in 2018.
METHODS: Two large cohorts were included in this analysis. One consisted of
45,856 PDAC patients in the Surveillance, Epidemiology, and End Results (SEER)
database (2004-2014), and the other consisted of 3166 PDAC patients in the Fudan
University Shanghai Cancer Center (FUSCC) database (2005-2015). RESULTS: Using
the 8th AJCC staging system, the median overall survival of the patients in the
same stage varied widely among the different substages. We proposed a modified
staging system based on median OS in which we maintained the T, N, and M
definitions, but regrouped the substages. In the SEER cohort, the concordance
index was higher for local disease with the modified staging system [0.637; 95%
confidence interval (CI) 0.631-0.642] than with the 8th AJCC staging system
(0.620, 95% CI 0.615-0.626). Similar findings were also observed in the FUSCC
cohort. In addition, we verified the reliability of the modified staging system
in an analysis of patients with different examined lymph node counts (>=15 or 1
14). CONCLUSIONS: The modified 8th AJCC staging system for PDAC proposed in this
study provides improvements and may be evaluated for potential adoption in the
next edition.
PMID- 29334561
TI - Preoperative 18F-FDG PET/CT in Pheochromocytomas and Paragangliomas Allows for
Precision Surgery.
AB - BACKGROUND: Fluorodeoxyglucose (F-FDG) positron emission tomography/computed
tomography (PET/CT) imaging is recommended in patients with metastatic
pheochromocytoma (PC) and paraganglioma (PGL). There are no data on whether
routine preoperative F-FDG PET/CT in all patients with PC/PGL impacts surgical
management. OBJECTIVE: The aim of this study was to determine whether routine
preoperative F-FDG PET/CT imaging affects the surgical management of patients
with PC/PGLs. METHODS: We analyzed clinical, biochemical, genetic, and anatomic
imaging data in 93 consecutive patients with PC/PGL who collectively underwent a
total of 100 operations and who had preoperative F-FDG PET/CT imaging. RESULTS:
Of 100 operations, preoperative F-FDG PET/CT showed additional lesions compared
to anatomic imaging in 15 cases. These patients were more likely to undergo an
open surgical approach (P < 0.05). Presence of genetic mutation, redo operations,
sex, age, or tumor size had no significant association with finding additional
lesions on F-FDG PET/CT. CONCLUSIONS: Additional lesions detected on preoperative
F-FDG-PET/CT imaging have an impact on the surgical approach in patients with
PC/PGLs. Therefore, surgeons should routinely obtain F-FDG-PET/CT imaging in
patients with PC/PGL to allow for a more precise surgical intervention.
PMID- 29334563
TI - Response to the Letter to the Editor by CM den Bakker and DL van Der Peet.
PMID- 29334562
TI - Is a Pathological Complete Response Following Neoadjuvant Chemoradiation
Associated With Prolonged Survival in Patients With Pancreatic Cancer?
AB - OBJECTIVES: To describe the survival outcome of patients with borderline
resectable or locally advanced pancreatic ductal adenocarcinoma (BR/LA-PDAC) who
have a pathologic complete response (pCR) following neoadjuvant chemoradiation.
BACKGROUND: Patients with BR/LA-PDAC are often treated with neoadjuvant
chemoradiation in an attempt to downstage the tumor. Uncommonly, a pCR may
result. METHODS: A retrospective review of a prospectively maintained database
was performed at a single institution. pCR was defined as no viable tumor
identified in the pancreas or lymph nodes by pathology. A near complete response
(nCR) was defined as a primary tumor less than 1 cm, without nodal metastasis.
Overall survival (OS) and disease-free survival (DFS) were reported. RESULTS: One
hundred eighty-six patients with BR/LA-PDAC underwent neoadjuvant chemoradiation
and subsequent pancreatectomy. Nineteen patients (10%) had a pCR, 29 (16%) had an
nCR, and the remaining 138 (74%) had a limited response. Median DFS was 26 months
in patients with pCR, which was superior to nCR (12 months, P = 0.019) and
limited response (12 months, P < 0.001). The median OS of nCR (27 months, P =
0.003) or limited response (26 months, P = 0.001) was less than that of pCR (more
than 60 months). In multivariable analyses pCR was an independent prognostic
factor for DFS (HR = 0.45; 0.22-0.93, P = 0.030) and OS (HR=0.41; 0.17-0.97, P =
0.044). Neoadjuvant FOLFIRINOX (HR=0.47; 0.26-0.87, P = 0.015) and negative lymph
node status (HR=0.57; 0.36-0.90, P = 0.018) were also associated with improved
survival. CONCLUSIONS: Patients with BR/LA-PDAC who had a pCR after neoadjuvant
chemoradiation had a significantly prolonged survival compared with those who had
nCR or a limited response.
PMID- 29334564
TI - Validating the Electronic Cardiac Arrest Risk Triage (eCART) Score for Risk
Stratification of Surgical Inpatients in the Postoperative Setting: Retrospective
Cohort Study.
AB - OBJECTIVE: Assess the accuracy of 3 early warning scores for predicting severe
adverse events in postoperative inpatients. SUMMARY OF BACKGROUND DATA:
Postoperative clinical deterioration on inpatient hospital services is associated
with increased morbidity, mortality, and cost. Early warning scores have been
developed to detect inpatient clinical deterioration and trigger rapid response
activation, but knowledge regarding the application of early warning scores to
postoperative inpatients is limited. METHODS: This was a retrospective cohort
study of adult patients hospitalized on the wards after surgical procedures at an
urban academic medical center from November, 2008 to January, 2016. The
accuracies of the Modified Early Warning Score (MEWS), National Early Warning
Score (NEWS), and the electronic cardiac arrest risk triage (eCART) score were
compared in predicting severe adverse events (ICU transfer, ward cardiac arrest,
or ward death) in the postoperative period using the area under the receiver
operating characteristic curve (AUC). RESULTS: Of the 32,537 patient admissions
included in the study, 3.8% (n = 1243) experienced a severe adverse outcome after
the procedure. The accuracy for predicting the composite outcome was highest for
eCART [AUC 0.79 (95% CI: 0.78-0.81)], followed by NEWS [AUC 0.76 (95% CI: 0.75
0.78)], and MEWS [AUC 0.75 (95% CI: 0.73-0.76)]. Of the individual vital signs
and labs, maximum respiratory rate was the most predictive (AUC 0.67) and maximum
temperature was an inverse predictor (AUC 0.46). CONCLUSION: Early warning scores
are predictive of severe adverse events in postoperative patients. eCART is
significantly more accurate in this patient population than both NEWS and MEWS.
PMID- 29334565
TI - Reversal of Intestinal Failure in Children With Tufting Enteropathy Supported
With Parenteral Nutrition at Home.
AB - OBJECTIVES: The aim of the study was to review long-term outcome of intestinal
epithelial dysplasia (IED)/tufting enteropathy (TE) patients treated with
parenteral nutrition (PN) at home managed by an intestinal failure (IF)
rehabilitation service. METHODS: Infants presenting from 1986 to 2010 with IF,
and TE histology were retrospectively reviewed for up to 30 years. Data collected
included outcome, presentation, nutrition (parenteral/enteral), country of
residence, race, EpCAM gene, growth, bone age, and occupation. RESULTS: Thirteen
patients (6 boys) in Malta and the UK with TE histology were established on home
PN. Survival was 100% for UK children and 92% overall (1 death aged 13 months).
Six patients (50% of the surviving 12) weaned off PN. Overall PN requirements
reduced with increasing age and <7 infusions/week were needed by 10/12, 83% by 10
years, 6/8, 75% who had reached 15 years, 5/7, 71% who had reached 20, and all 4,
100% >25 years. Two of 12 cases weaned from PN by 10 years, 1 of 8 by 15 years, 3
of 7 by 20 years, and 3 of 4 or 75% >25 years. Seven Maltese patients homozygous
for the same EPCAM gene abnormality had a similar outcome to the other cases.
Weight, height, bone mineralization, bone age, and insulin-like growth factor-1
(IGF-1) levels were low, but improved with age. Patients achieved educational
levels of parents and were employed. CONCLUSIONS: IED cases should have >92%
chance of long-term survival and >50% chance of enteral autonomy by/in early
adult life and 75% by 25 years. Even if PN dependent s/he can gain employment.
Patients with IED managed on PN at home by an IF rehabilitation service should
avoid intestinal transplant.
PMID- 29334566
TI - Deficiency of transforming growth factor-beta signaling disrupts memory processes
in rats.
AB - Cytokines, in addition to their participation in immune and inflammatory
processes, play an important role in synaptic plasticity, neoneurogenesis, and
cognitive functions. In our work, we aimed to clarify the role of the
transforming growth factor-beta (TGF-beta), which is recognized as a
multifunctional cytokine, in memory processes. Behavioral experiments were
carried out in rats using step-through passive avoidance test. The results
obtained showed that the learning of animals after treatment with SB431542, a
selective inhibitor of TGF-beta receptors, was impaired, which indicated a
significant memory deterioration. Nevertheless, the memory of rats remained at
the control level when TGF-beta and SB431542 were coadministered. Thus, the role
of TGF-beta in memory retrieval after the passive avoidance test was revealed:
memory in rats was weakened if the TGF-beta signaling pathway was inhibited
during learning. Evidently, successful consolidation of at least some types of
memory requires a normal level of TGF-beta, indicating the modulation of
cognitive functions by cytokines under normal physiological conditions.
PMID- 29334567
TI - Pediatric vascular trauma practice patterns and resource availability: A survey
of American College of Surgeon-designated pediatric trauma centers.
AB - BACKGROUND: Variation exists in pediatric vascular trauma management. We aim to
determine practice patterns for vascular trauma management at American College of
Surgeons verified pediatric trauma centers and evaluate the resources available
for management of vascular trauma at both freestanding children's hospitals
(FSCH) and pediatric hospitals within general adult hospitals. METHODS: Pediatric
surgeons and trauma medical directors at American College of Surgeons designated
pediatric surgery trauma centers completed a survey designed to evaluate
anticipated management of traumatic arterial injuries and resource availability.
Hospital setting comparisons were made using Fisher exact tests and t tests.
Binomial tests were used to compare pediatric and vascular surgeons' responses to
clinical vignettes. p Values of 0.05 or less were significant. RESULTS: One
hundred seventy-six (42%) of 414 pediatric surgeons participated. Vascular
surgeons are more likely to operatively manage vascular trauma at all anatomic
sites except subclavian artery when compared to pediatric surgeons, regardless of
hospital setting (p <0.001). Forty-eight percent of the pediatric trauma medical
directors completed their portion of the survey. At FSCHs, 36% did not have a
fellowship-trained vascular surgeon on-call schedule, 27% did not have
endovascular capabilities, and 18% did not have a radiology technologist always
available. CONCLUSION: Vascular surgeons are more likely to manage pediatric
vascular trauma regardless of hospital setting. However, FSCH have fewer
resources available to provide optimal care. LEVEL OF EVIDENCE: Care management,
level IV.
PMID- 29334568
TI - Goal-directed hemostatic resuscitation for trauma induced coagulopathy:
Maintaining homeostasis.
PMID- 29334569
TI - Assessment of prehospital hemorrhage and airway care using a simulation model.
AB - BACKGROUND: The quality of prehospital care impacts patient outcomes. Military
efforts have focused on training revision and the creation of high-fidelity
simulation models to address potentially survivable injuries. We sought to
investigate the applicability of models emphasizing hemorrhage control and airway
management to a civilian population. METHODS: Prehospital health care providers
(PHPs) undergoing their annual training were enrolled. A trauma scenario was
simulated with two modules: hemorrhage control and airway management. Experienced
raters used a validated tool to assess performance. Pearson correlation, logistic
regression, and chi tests were used for analysis. RESULTS: Ninety-five PHPs
participated with a mean experience of 15.9 +/- 8.3 years, and 7.4% reported past
military training. The PHPs' overall execution rate of the six hemorrhage control
measures varied from 38.9% to 88.4%. The median blood loss was 1,700 mL
(interquartile range, 1,043-2,000), and the mean global rater score was 25.0 +/-
7.4 (scale, 5-40). There was a significant relationship between PHP profession
and past military experience to their consideration of blood transfusion and
tranexamic acid. An inverse relationship between blood loss and global rater
score was found (r = -0.59, n = 88, p = 1.93 * 10). After simulated direct
laryngoscope failure in the airway module, 58% of PHPs selected video
laryngoscopy over placement of a supraglottic airway. Eighty-six percent of
participants achieved bilateral chest rise in the manikin regardless of
management method. Participants reported improved comfort with skills after
simulation. CONCLUSION: Our data reveal marginal performance in hemorrhage
control regardless of the PHP's prior experience. The majority of PHPs were able
to secure an advanced airway if direct laryngoscope was unavailable with a
predisposition for video laryngoscopy over supraglottic airway. Our findings
support the need for continued training for PHPs highlighting hemorrhage control
maneuvers and increased familiarity with airway management options. Improved
participant confidence posttraining gives credence to simulation training. LEVEL
OF EVIDENCE: Prognostic/epidemiological study, level III.
PMID- 29334570
TI - The effect of prehospital transport time, injury severity, and blood transfusion
on survival of US military casualties in Iraq.
AB - BACKGROUND: Reducing time from injury to care can optimize trauma patient
outcomes. A previous study of prehospital transport of US military casualties
during the Afghanistan conflict demonstrated the importance of time and treatment
capability for combat casualty survival. METHODS: A retrospective descriptive
analysis was conducted to analyze battlefield data collected on US military
combat casualties during the Iraq conflict from March 19, 2003, to August 31,
2010. All casualties were analyzed by mortality outcome (killed in action, died
of wounds, case fatality rate) and compared with Afghanistan conflict. Detailed
data for those who underwent prehospital transport were analyzed for effects of
transport time, injury severity, and blood transfusion on survival. RESULTS: For
the total population, percent killed in action (16.6% vs. 11.1%), percent died of
wounds (5.9% vs. 4.3%), and case fatality rate (10.0 vs. 8.6) were higher for
Iraq versus Afghanistan (p < 0.001). Among 1,692 casualties (mean New Injury
Severity Score, 22.5; mortality, 17.6%) with detailed data, the injury mechanism
included 77.7% from explosions and 22.1% from gunshot wounds. For prehospital
transport, 67.6% of casualties were transported within 60 minutes, and 32.4% of
casualties were transported in greater than 60 minutes. Although 97.0% of deaths
occurred in critical casualties (New Injury Severity Score, 25-75), 52.7% of
critical casualties survived. Critical casualties were transported more rapidly
(p < 0.01) and more frequently within 60 minutes (p < 0.01) than other
casualties. Critical casualties had lower mortality when blood was received (p <
0.01). Among critical casualties, blood transfusion was associated with survival
irrespective of transport time within or greater than 60 minutes (p < 0.01).
CONCLUSION: Although data were limited, early blood transfusion was associated
with battlefield survival in Iraq as it was in Afghanistan. LEVEL OF EVIDENCE:
Performance improvement and epidemiological, level IV.
PMID- 29334571
TI - Use of French lyophilized plasma transfusion in severe trauma patients is
associated with an early plasma transfusion and early transfusion ratio
improvement.
AB - BACKGROUND: Early transfusion of high ratio of fresh frozen plasma (FFP) and red
blood cells (RBC) is associated with mortality reduction. However, time to reach
high ratio is limited by the need to thaw the FFP. French lyophilized plasma
(FLYP) used by French army and available in military teaching hospital does not
need to be thawed and is immediately available. We hypothesize that the use of
FLYP may reduce time to reach a plasma/RBC ratio of 1:1. METHODS: A retrospective
study performed in a Level 1 trauma center between January 2012 and December
2015. Severe trauma patients who received 2 U of RBC in the emergency room were
included and assigned to two groups according to first plasma transfused: FLYP
group and FFP group. RESULTS: Forty-three severe trauma patients in the FLYP
group and 29 in the FFP group were included. The time until first plasma
transfusion was shorter in the FLYP group than in the FFP group, respectively 15
min (10-25) versus 95 min (70-145) (p < 0.0001). Time until a 1:1 ratio was
shorter in the FLYP group than in the FFP group. There were significantly fewer
cases of massive transfusion in the FLYP group than in the FFP group with
respectively 7% vs. 45% (p < 0.0001). CONCLUSION: The use of FLYP provided
significantly faster plasma transfusions than the use of FFP as well as a plasma
and RBC ratio superior to 1:2 that was reached more rapidly in severe trauma
patients. These results may explain the less frequent need for massive
transfusion in the patients who received FLYP. These positive results should be
confirmed by a prospective and randomized evaluation. LEVEL OF EVIDENCE:
Therapeutic, level IV.
PMID- 29334572
TI - Assessment of Parasympathetic Activity in Athletes: Comparing Two Different
Methods-RETRACTION.
PMID- 29334573
TI - A Fresh Cadaver Study on Indocyanine Green Fluorescence Lymphography: A New Whole
Body Imaging Technique for Investigating the Superficial Lymphatics.
AB - BACKGROUND: Identification of the lymphatic system in cadavers is painstaking
because lymphatic vessels have very thin walls and are transparent. Selection of
appropriate contrast agents is a key factor for successfully visualizing the
lymphatics. In this study, the authors introduce a new imaging technique of
lymphatic mapping in the whole bodies of fresh cadavers. METHODS: Ten fresh human
cadavers were used for this study. The authors injected 0.1 ml of indocyanine
green fluorescence solution subcutaneously at multiple spots along the watershed
lines between lymphatic territories and hand and foot regions. After the body was
scanned by the near-infrared camera system, fluorescent tissues were harvested
and histologic examination was performed under the microscope equipped with the
infrared camera system to confirm that they were the lymphatics. RESULTS:
Subcutaneously injected indocyanine green was immediately transported into the
lymphatic vessels after gentle massage on the injection points. Sweeping massage
along the lymphatic vessels facilitated indocyanine green transport inside the
lymphatic vessel to move toward the lymph nodes. The lymphatic system was
visualized well in the whole body. Histologic examinations confirmed that
indocyanine green was detected in the lymphatic lumens specifically, even when
located far from the injected points. CONCLUSIONS: The lymphatic system could be
visualized in whole-body fresh cadavers, as in living bodies, using indocyanine
green fluorescence lymphography. Compatibility of indocyanine green lymphography
would facilitate the use of cadaveric specimens for macroscopic and microscopic
analyses.
PMID- 29334574
TI - Improved Long-Term Volume Retention of Stromal Vascular Fraction Gel Grafting
with Enhanced Angiogenesis and Adipogenesis.
AB - BACKGROUND: The apoptosis of mature adipocytes after fat grafting can result in
chronic inflammation, absorption, and fibrosis, leading to unpredictable
outcomes. Selective elimination of mature adipocytes may result in better
outcomes and a different underlying retention mode. The authors previously
developed a mature adipocyte-free product, stromal vascular fraction gel, derived
from lipoaspirate, which eliminates adipocytes and preserves the stromal vascular
fraction. This study investigated the retention and regeneration mode of stromal
vascular fraction gel grafting. METHODS: Nude mice were grafted with human
derived stromal vascular fraction gel or Coleman fat. Detailed cellular events
over 3 months were investigated histologically and immunohistochemically.
RESULTS: The retention rate 90 days after grafting was significantly higher for
stromal vascular fraction gel grafts than for standard Coleman fat (82 +/- 15
percent versus 42 +/- 9 percent; p < 0.05). Histologic analysis suggested that,
unlike Coleman fat grafts, stromal vascular fraction gel grafts did not include
significant necrotic areas. Moreover, although adipose tissue regeneration was
found in grafts of both groups, rapid angiogenesis and macrophage infiltration
were observed at a very early stage after stromal vascular fraction gel grafting.
The presence of small preadipocytes with multiple intracellular lipid droplets in
stromal vascular fraction gel grafts on day 3 also suggested very early
adipogenesis. Although some of the cells in the stromal vascular fraction
survived in stromal vascular fraction gel grafts, most of the newly formed
adipose tissue was host-derived. CONCLUSION: Stromal vascular fraction gel has a
high long-term retention rate and a unique adipose regeneration mode, involving
prompt inflammation and infiltration of immune cells, stimulating rapid
angiogenesis and inducing host cell-mediated adipogenesis.
PMID- 29334575
TI - Measurement of Warping Angle in Human Rib Graft: An Experimental Study.
AB - BACKGROUND: The purpose of this study was to determine the warping angle of the
costal cartilage in vivo. METHODS: A nasal framework reconstruction with a rib
graft was performed in a total of 130 patients. After the cartilage specimens
were prepared, the remaining grafts were used for study. The angle of warping in
all grafts was measured at 0, 30, and 60 minutes; after 24 hours; and after 1
week. Eight subgroups of graft thicknesses from central and peripheral groups,
determined according to the perichondral distance of the grafts, were evaluated,
and the warping angles of 48 osteochondral and chondral grafts were measured
individually. Three-way analysis of variance was used to compare the change in
warping over time to detect differences in the grafts. RESULTS: Significant
differences were not observed in the 1- to 3-mm-thick grafts of peripheral and
central origin before 30 minutes (p > 0.05), although significant differences
were observed in these groups for all time points after 30 minutes (p < 0.05). In
central and peripheral grafts thicker than 4 mm, a significant warping angle was
not observed (p > 0.05). In central origin grafts thinner than 1 mm, significant
differences were not observed in the warping angle (p > 0.05), although they were
observed in the same grafts of peripheral origin (p < 0.05). Peripheral origin
grafts thicker than 1 mm showed warping in the direction of the perichondrium (p
< 0.05), whereas central origin grafts thinner than 1 mm showed warping angle
irregularities. CONCLUSION: Interlocking stresses are very important in rib
grafts when balanced cross-sectional carving occurs from the peripheral to the
central areas. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.
PMID- 29334576
TI - Cheek Volumization and the Nasolabial Fold.
AB - BACKGROUND: The impression that cheek filling results in longitudinal shortening
("lift") of the skin and elevation of the nasolabial crease or nasolabial fold
has become common within the facial injection community but remains
unsubstantiated. METHODS: In this study, 77 patients were evaluated before and
after injection of the cheeks with a hyaluronic acid filler using a three
dimensional camera system. RESULTS: A constant pattern of skin expansion away
from the center of the injection and perpendicular to the surface of the skin was
observed. A subgroup of 37 patients without differences in their preinjection and
postinjection facial expression were analyzed by direct comparison and failed to
demonstrate lateral traction (or "pull") on the intervening skin from the cheek
injection site to the nasolabial crease. Furthermore, there was no photographic
difference in the nasolabial fold or nasolabial crease. The only patients who
demonstrated photographic improvement of the medial face were those who had
filler placed directly in the transition between the lateral nasolabial fold and
cheek (nasojugal crease). CONCLUSIONS: Filling the cheek with 3 cc of volume does
not create traction forces or move the skin between the site of injection and the
nasolabial crease. It is likely that expanding the nasojugal crease is the direct
visual cue that leads to perceived improvement in the nasolabial fold.
PMID- 29334577
TI - Consequences of the F.D.A. Directed Moratorium on Silicone Gel Breast Implants -
1992-2006.
AB - The FDA silicone gel breast implant moratorium occurred 25 years ago. The
immediate and long-term consequences of the moratorium are reviewed and assessed.
PMID- 29334578
TI - Commentary on Norm Cole's "Moratorium Consequences."
PMID- 29334579
TI - Implementation of [18F]-labeled amyloid brain PET imaging biomarker in the
diagnosis of Alzheimer's disease: first-hand experience in Thailand.
PMID- 29334580
TI - Load-Power Relationship During a Countermovement Jump: A Joint Level Analysis.
AB - Williams, KJ, Chapman, DW, Phillips, EJ, and Ball, N. Load-power relationship
during a countermovement jump: A joint level analysis. J Strength Cond Res 32(4):
955-961, 2018-This study aimed to investigate whether hip, knee, and ankle peak
power is influenced by the relative load lifted, altering the joint and system
load-power relationship during a countermovement jump (CMJ). Twenty-three male
national representative athletes (age: 20.3 +/- 3.1 years, squat 1 repetition
maximum [1RM]: 133.8 +/- 24.8 kg) completed 3 CMJs at relative barbell loads of
0, 10, 20, 30, and 40% of an athlete's estimated back squat 1RM. Ground reaction
force and joint kinematics were captured using a 16 camera motion capture array
integrated with 2 in-ground triaxial force plates. Hip ((Equation is included in
full-text article.)= 20%, range 0 > 40%), knee ((Equation is included in full
text article.)= 0%, 0 > 20%), and ankle ((Equation is included in full-text
article.)= 40%, 0 > 40%) peak power was maximized at different percentages of
absolute strength, with an athlete-dependent variation in load-power profiles
observed across all lower-body joints. A decrease in system (body + barbell mass)
peak power was significantly (p <= 0.05, r = 0.45) correlated with a reduction in
knee peak power. Timing of instantaneous system and hip peak power occurred
significantly closer to toe-off as load increased. The findings highlight that
the generation and translation of lower-body joint power is influenced by
external load and athlete-dependent traits. This subsequently alters the load
power profile at a system level, explaining the broad spectrums of loads reported
to optimize system power during a CMJ. When training, we recommend that a
combination of barbell loads based on assorted percentages of the estimated 1RM
be prescribed to optimize joint and system power during a CMJ.
PMID- 29334581
TI - Gender- and Muscle-Specific Responses During Fatiguing Exercise.
AB - Hill, EC, Housh, TJ, Smith, CM, Schmidt, RJ, and Johnson, GO. Gender- and muscle
specific responses during fatiguing exercise. J Strength Cond Res 32(5): 1471
1478, 2018-The purpose of the present investigation was to examine potential
gender-related differences in electromyographic (EMG) and mechanomyographic (MMG)
responses during submaximal, concentric, isokinetic, forearm flexion muscle
contractions. Twelve men and 12 women performed concentric peak torque trials
before (pretest) and after (posttest) a fatiguing exercise bout that consisted of
50 submaximal (65% of concentric peak torque), concentric, isokinetic (60 degrees
.s), forearm flexion muscle contractions. Surface EMG and MMG signals were
simultaneously recorded from the biceps brachii and brachioradialis muscles.
There was a gender-related difference in the decline in absolute concentric peak
torque for the men (23.8%) vs. women (18.5%) that was eliminated when covaried
for differences in pretest concentric peak torque values. During the fatiguing
exercise bout, EMG amplitude(AMP) increased and EMG mean power frequency (MPF)
decreased for both genders and muscles. There were, however, muscle- and gender
specific increases, decreases, and no changes for MMG AMP and MMG MPF. The gender
related difference for the posttest decline in concentric peak torque was
associated with differences in muscle strength which may have resulted in greater
blood flow occlusion in the men than the women. The muscles with the most
pronounced fatigue-induced neuromuscular responses were the biceps brachii in men
and the brachioradialis in women. These findings may be related to gender
differences in the usage patterns of synergistic muscles during a fatiguing task.
PMID- 29334582
TI - Carbohydrate Mouth Rinsing Does Not Prevent the Decline in Maximal Strength After
Fatiguing Exercise.
AB - Black, CD, Schubert, DJ, Szczyglowski, MK, and Wren, JD. Carbohydrate mouth
rinsing does not prevent the decline in maximal strength after fatiguing
exercise. J Strength Cond Res 32(9): 2466-2473, 2018-Carbohydrate (CHO) rinsing
has been shown to attenuate the decline of maximal voluntary contractions (MVCs)
after fatiguing exercise-perhaps through a central mechanism. This study sought
to determine the effect of a CHO rinse on MVC, voluntary activation, and
contractile properties after fatiguing exercise. Thirteen adults participated in
a double-blind, cross-over study. Maximal voluntary contraction of the dominant
knee extensors was assessed, and voluntary activation (%VA) was determined using
twitch interpolation. Participants then held 50% of MVC until volitional fatigue
followed by a 20-second rinse with a solution of 8% maltodextrin (CHO) or placebo
(PLA). Maximal voluntary contraction and %VA were reassessed immediately and 5
minutes after exercise. Maximal voluntary contraction did not differ between the
CHO and PLA conditions initially (230 +/- 90 vs. 232 +/- 90 N.m; p = 0.69).
Maximal voluntary contraction declined after exercise (p <= 0.01), but no
differences were found between the CHO and PLA conditions (p >= 0.59). %VA did
not differ between conditions (91.9 +/- 2.9% vs. 91.5 +/- 3.8%; p >= 0.11) nor
did it change after exercise (p = 0.57). Twitch torque, rate of torque
development, and rate of torque relaxation were reduced after exercise (p <=
0.05) but were unaffected by CHO rinsing (p > 0.05). Unlike a previous study, a
CHO rinse did not preserve MVC after fatiguing exercise. This was likely due to a
lack of central fatigue induced by the exercise protocol (as %VA was unaffected)
as the CHO rinse is thought to work through a central mechanism.
PMID- 29334583
TI - Effects of Carnosine (Beta-Alanyl-L-Histidine) in an Experimental Rat Model of
Acute Kidney Injury Due to Septic Shock.
AB - BACKGROUND Acute kidney injury (AKI) secondary to sepsis is a major cause of
morbidity and mortality in the human intensive care unit (ICU). Kidney function
and the histological findings of AKI were investigated in an experimental rat
model with sepsis induced by cecal ligation and puncture (CLP) and compared with
and without treatment with carnosine (beta-alanyl-L-histidine). MATERIAL AND
METHODS Twenty-four Sprague-Dawley rats were randomly divided into three groups
consisting eight rats in each: Group 1 - control; Group 2 - septic shock; and
Group 3 - septic shock treated with carnosine. Femoral vein and artery
catheterization were applied in all rats. Rats in Group 1 underwent laparotomy
and catheterization. The other two groups with septic shock underwent laparotomy,
CLP, catheterization, and bladder cannulation. Rats in Group 3 received an
intraperitoneal (IP) injection of 250 mg/kg carnosine, 60 min following CLP. Rats
were monitored for blood pressure, pulse rate, and body temperature to assess
responses to postoperative sepsis, and 10 mL/kg saline replacement was
administered. Twenty-four hours following CLP, rats were sacrificed, and blood
and renal tissue samples were collected. RESULTS Statistically significant
improvements were observed in kidney function, tissue and serum malondialdehyde
levels, routine blood values, biochemical indices, and in histopathological
findings in rats in Group 3 who were treated with carnosine, compared with Group
2 exposed to septic shock without carnosine treatment. CONCLUSIONS Carnosine
(beta-alanyl-L-histidine) has been shown to have beneficial effects in reducing
AKI due to septic shock in a rat model of septicemia.
PMID- 29334584
TI - In vitro and in vivo metabolite identification of a novel benzimidazole compound
ZLN005 by LC-MS/MS.
AB - RATIONALE: A novel benzimidazole compound ZLN005 was previously identified as a
transcriptional activator of peroxisome proliferator-activated receptor gamma
coactivator 1alpha (PGC-1alpha) in certain metabolic tissues. Upregulation of PGC
1alpha by ZLN005 has been shown to have beneficial effect in a diabetic mouse
model and in a coronary artery disease model in vitro. ZLN005 could also have
therapeutic potential in neurodegenerative diseases involving down-regulation of
PGC-1alpha. Given the phenotypic efficacy of ZLN005 in several animal models of
human disease, its metabolic profile was investigated to guide the development of
novel therapeutics using ZLN005 as the lead compound. METHODS: ZLN005 was
incubated with both rat and human liver microsomes and S9 fractions to identify
in vitro metabolites. Urine from rats dosed with ZLN005 was used to identify in
vivo metabolites. Extracted metabolites were analyzed by LC-MS/MS using a hybrid
linear ion trap triple quadrupole mass spectrometer under full scan, enhanced
product ion scan, neutral loss scan and precursor scan modes. Metabolites in
plasma and brain of ZLN005-treated rats were also profiled using multiple
reaction monitoring. RESULTS: Identified in vitro transformations of ZLN005
include mono- and dihydroxylation, further oxidation to carboxylic acids, and
mono-O-glucuronide and sulfate conjugation to hydroxy ZLN005 as well as
glutathione conjugation. Identified in vivo metabolites are mainly glucuronide
and sulfate conjugates of dihydroxyl, carboxyl, and hydroxy acid of the parent
compound. The parent compound as well as several major phase I metabolites were
found in rat plasma and brain. CONCLUSIONS: Using both in vitro and in vivo
methods, we elucidated the metabolic pathway of ZLN005. Phase I metabolites with
hydroxylation and carboxylation, as well as phase II metabolites with
glucuronide, sulfate and glutathione conjugation, were identified.
PMID- 29334585
TI - Naturally occurring chrysophanol as matrix-assisted laser desorption ionization
matrix for the analysis of a broad spectrum of analytes.
PMID- 29334587
TI - Systolic blood pressure as a potential target of sigma-1 receptor agonist
therapy.
PMID- 29334586
TI - A Non-Heme Iron Photocatalyst for Light-Driven Aerobic Oxidation of Methanol.
AB - Non-heme (L)FeIII and (L)FeIII -O-FeIII (L) complexes (L=1,1-di(pyridin-2-yl)-N,N
bis(pyridin-2-ylmethyl)ethan-1-amine) underwent reduction under irradiation to
the FeII state with concomitant oxidation of methanol to methanal, without the
need for a secondary photosensitizer. Spectroscopic and DFT studies support a
mechanism in which irradiation results in charge-transfer excitation of a FeIII
MU-O-FeIII complex to generate [(L)FeIV =O]2+ (observed transiently during
irradiation in acetonitrile), and an equivalent of (L)FeII . Under aerobic
conditions, irradiation accelerates reoxidation from the FeII to the FeIII state
with O2 , thus closing the cycle of methanol oxidation to methanal.
PMID- 29334588
TI - Molecular Wire Effects in Phenyleneethynylene Oligomers: Surprising Insights.
AB - The synthesis and quenching behavior of a series of water-soluble, carboxylate
carrying phenyleneethynylene oligomers-monomer to tetramer-and their polymers are
reported; their quenching behavior with different test analytes (paraquat, lead
salts, mercury salts, picric acid, methylpyridinium iodide) in water were
investigated, and the results were compared to that of the conjugated polymer.
Significant but analyte-dependent enhancement effects were found. For monovalent
quenchers, only the molecular wire effect applies, but for divalent quenchers
multivalency effects are also important.
PMID- 29334589
TI - Preparation and evaluation of a deoxycholic-calix[4]arene hybrid-type receptor as
a chiral stationary phase for HPLC.
AB - We report the synthesis and enantioseparation characteristics of two novel
covalently immobilized deoxycholic acid derivatives as chiral stationary phases
for high-performance liquid chromatography. In the structure of the first
stationary phase, the 3-position of deoxycholic acid is substituted with a 3,5
dinitrophenylcarbamoyl group and the second one has an additional calix[4]arene
attached to the carboxylic group of the deoxycholic acid. The chromatographic
performance of the stationary phases was evaluated with enantioseparation of N
(3,5-dinitrobenzoyl)-dl-leucine, N-(3,5-dinitrobenzoyl)-dl-valine, omeprazole,
diclofop-methyl, dl-mandelic acid and (RS)-pregabalin. Comparison of the
performance characteristics of the prepared chiral stationary phases provided
evidence for the active involvement of the calix[4]arene unit in the chiral
recognition process. Both stationary phases are chemically bonded to the silica
and can be used in both normal-phase and reversed-phase modes.
PMID- 29334590
TI - Highly Dispersible and Bioavailable Curcumin but not Native Curcumin Induces
Brown-Like Adipocyte Formation in Mice.
AB - SCOPE: The induction of brown-like adipocytes in white adipose tissue (WAT) is a
potential therapeutic target for the treatment of obesity and metabolic disorders
via the ability of these cells to release excess energy as heat in association
with uncoupling protein 1. Some experimental trials suggest that curcumin (a
yellow pigment from turmeric) has a suppressive effect on the accumulation of
body fat. However, there is little evidence to show that curcumin induces the
formation of brown-like adipocytes and the molecular mechanisms involved remain
elusive. In addition, in most experimental trials, high doses of curcumin are
administered. METHODS AND RESULTS: Highly dispersible and bioavailable curcumin
(HC, i.e., 4.5 mg native curcumin kg-1 ) but not the same dose of native curcumin
induces the formation of brown-like adipocytes in mouse inguinal WAT. Moreover,
the formation of brown-like adipocytes induced by HC in inguinal WAT may be
mediated by the production of local norepinephrine from accumulated alternatively
activated macrophages. CONCLUSION: These novel findings suggest that curcumin
increases energy expenditure by inducing the formation of brown-like adipocytes
via a unique molecular mechanism. Importantly, they show that HC has significant
bioactive effects in vivo at lower doses of curcumin.
PMID- 29334591
TI - GTEx project maps wide range of normal human genetic variation: A unique catalog
and follow-up effort associate variation with gene expression across dozens of
body tissues.
PMID- 29334593
TI - Reanalysis of clinical whole-exome sequence data yields multiple new diagnoses: A
time-intensive but successful strategy highlights the benefits of data sharing
and international collaborations.
PMID- 29334594
TI - Thoracic aortic aneurysm in patients with loss of function Filamin A mutations:
Clinical characterization, genetics, and recommendations.
AB - The frequency and gender distribution of thoracic aortic aneurysm as a
cardiovascular manifestation of loss-of-function (LOF) X-linked FilaminA (FLNA)
mutations are not known. Furthermore, there is very limited cardiovascular
morbidity or mortality data in children and adults. We analyzed cardiac data on
the largest series of 114 patients with LOF FLNA mutations, both children and
adults, with periventricular nodular heterotopia (PVNH), including 48 study
patients and 66 literature patients, median age of 22.0 years (88 F, 26 M, range:
0-71 years), with 75 FLNA mutations observed in 80 families. Most (64.9%)
subjects had a cardiac anomaly or vascular abnormality (80.8% of males and 60.2%
of females). Thoracic aortic aneurysms or dilatation (TAA) were found in 18.4% (n
= 21), and were associated with other structural cardiac malformations in 57.1%
of patients, most commonly patent ductus arteriosus (PDA) and valvular
abnormalities. TAA most frequently involved the aortic root and ascending aorta,
and sinus of Valsalva aneurysms were present in one third of TAA patients. Six
TAA patients (28.5%) required surgery (median age 37 yrs, range 13-41 yrs). TAA
with its associated complications was also the only recorded cause of premature,
non-accidental mortality in adults (2 M, 2 F). Two adult patients (1 F, 1 M,
median 38.5 yrs), died of spontaneous aortic rupture at aortic dimensions smaller
than current recommendations for surgery for other aortopathies. Data from this
largest series of LOF FLNA mutation patients underscore the importance of serial
follow-up to identify and manage these potentially devastating cardiovascular
complications.
PMID- 29334596
TI - The diversifying field of plant epigenetics.
PMID- 29334597
TI - Monitoring global tree mortality patterns and trends. Report from the VW
symposium 'Crossing scales and disciplines to identify global trends of tree
mortality as indicators of forest health'.
PMID- 29334599
TI - Sofia J. van Moorsel.
PMID- 29334598
TI - Time to re-think fungal ecology? Fungal ecological niches are often prejudged.
PMID- 29334600
TI - Probing promise versus performance in longer read fungal metabarcoding.
PMID- 29334601
TI - Out of sight, but no longer out of mind - towards an increased recognition of the
role of soil microbes in plant speciation.
PMID- 29334602
TI - High-Dose Metformin Plus Temozolomide Shows Increased Anti-tumor Effects in
Glioblastoma In Vitro and In Vivo Compared with Monotherapy.
AB - PURPOSE: The purpose of the study is to investigate the efficacy of combined
treatment with temozolomide (TMZ) and metformin for glioblastoma (GBM) in vitro
and in vivo. Materials and Methods: We investigated the efficacy of combined
treatment with TMZ and metformin using cell viability and apoptosis assays. A GBM
orthotopic mice model was established by inoculation of 5*105 U87 cells and
treatedwith metformin, TMZ, and the combination for 4weeks. Western blotting and
immunofluorescence of tumor specimens were analyzed to investigate AMP-activated
protein kinase (AMPK) and AKT pathway. RESULTS: The combination of TMZ and
metformin showed higher cytotoxicity than single agents in U87, U251, and A172
cell lines. A combination of high-dose metformin and TMZ showed the highest
apoptotic activity. The combination of TMZ and metformin enhanced AMPK
phosphorylation and inhibited mammalian target of rapamycin phosphorylation, AKT
phosphorylation, and p53 expression. The median survival of each group was 43.6,
55.2, 53.2, 65.2, and 71.3 days for control, metformin treatment (2 mg/25 g/day
or 10 mg/25 g/day), TMZ treatment (15 mg/kg/day), combination treatment with low
dose metformin and TMZ, and combination treatment with high-dose metformin and
TMZ, respectively. Expression of fatty acid synthase (FASN) was significantly
decreased in tumor specimens treated with metformin and TMZ. CONCLUSION: The
combination of metformin and TMZ was superior to monotherapy using metformin or
TMZ in terms of cell viability in vitro and survival in vivo. The combination of
high-dose metformin and TMZ inhibited FASN expression in an orthotopic model.
Inhibition of FASN might be a potential therapeutic target of GBM.
PMID- 29334603
TI - Multicenter Phase II Study of Oxaliplatin, Irinotecan, and S-1 as First-line
Treatment for Patients with Recurrent or Metastatic Biliary Tract Cancer.
AB - PURPOSE: Although gemcitabine plus cisplatin has been established as the standard
first-line chemotherapy for patients with advanced biliary tract cancer (BTC),
overall prognosis remains poor. We investigated the efficacy of a novel triplet
combination of oxaliplatin, irinotecan, and S-1 (OIS) for advanced BTC. Materials
and Methods: Chemotherapy-naive patientswith histologically documented
unresectable or metastatic BTC were eligible for this multicenter, single-arm
phase II study. Patients received 65 mg/m2 oxaliplatin (day 1), 135 mg/m2
irinotecan (day 1), and 40 mg/m2 S-1 (twice a day, days 1-7) every 2 weeks.
Primary endpoint was objective response rate. Targeted exome sequencing for
biomarker analysis was performed using archival tissue. RESULTS: In total, 32
patients were enrolled between October 2015 and June 2016. Median age was 64
years (range, 40 to 76 years), with 24 (75%) male patients; 97% patients had
metastatic or recurrent disease. Response rate was 50%, and median progression
free survival and overall survival (OS) were 6.8 months (95% confidence interval
[CI], 4.8 to 8.8) and 12.5 months (95% CI, 7.0 to 18.0), respectively. The most
common grade 3-4 adverse events were neutropenia (32%), diarrhea (6%), and
peripheral neuropathy (6%). TP53 and KRAS mutations were the most frequent
genomic alterations (42% and 32%, respectively), and KRAS mutations showed a
marginal relationship with worse OS (p=0.07). CONCLUSION: OIS combination
chemotherapy was feasible and associated with favorable efficacy outcomes as a
first-line treatment in patients with advanced BTC. Randomized studies are needed
to compare OIS with gemcitabine plus cisplatin.
PMID- 29334604
TI - Breast Conservation Therapy Versus Mastectomy in Patients with T1-2N1 Triple
Negative Breast Cancer: Pooled Analysis of KROG 14-18 and 14-23.
AB - PURPOSE: The aim of this study is to compare the treatment outcomes of breast
conserving surgery (BCS) plus radiotherapy (RT) versus mastectomy for patients
with pT1-2N1 triple-negative breast cancer (TNBC). Materials and Methods: Using
two multicenter retrospective studies on breast cancer, a pooled analysis was
performed among 320 patients with pT1-2N1 TNBC. All patients who underwent BCS
(n=212) receivedwhole breast RTwith orwithoutregional nodal RT,while nonewho
underwent mastectomy (n=108)received it. All patients received taxane-based
adjuvant chemotherapy. The median follow-up periods were 65 months in the BCS+RT
group, and 74 months in the mastectomy group. RESULTS: The median age of all
patients was 48 years (range, 24 to 70 years). Mastectomy group had more patients
with multiple tumors (p < 0.001), no lymphovascular invasion (p=0.001), higher
number of involved lymph node (p=0.028), and higher nodal ratio >= 0.2 (p=0.037).
Other characteristics were not significantly different between the two groups.
The 5-year locoregionalrecurrence-free, disease-free, and overall survivalrates
of BCS+RT group versus mastectomy group were 94.6% versus 87.7%, 89.5% versus
80.4%, and 95.0% versus 87.8%, respectively, and the differences were
statistically significant after adjusting for covariates (p=0.010, p=0.006, and
p=0.005, respectively). CONCLUSION: In pT1-2N1 TNBC, breast conservation therapy
achieved better locoregional recurrencefree, disease-free, and overall survival
rates compared with mastectomy.
PMID- 29334605
TI - Induction Chemotherapy Plus Concurrent Chemoradiotherapy Versus Concurrent
Chemoradiotherapy Alone in Locoregionally Advanced Nasopharyngeal Carcinoma in
Children and Adolescents: A Matched Cohort Analysis.
AB - PURPOSE: The purpose of this study was to evaluate the long-term clinical outcome
and toxicity of induction chemotherapy (IC) followed by concomitant
chemoradiotherapy (CCRT) compared with CCRT alone for the treatment of children
and adolescent locoregionally advanced nasopharyngeal carcinoma (LACANPC).
Materials and Methods: A total of 194 locoregionally advanced nasopharyngeal
carcinoma patients youngerthan 21 years who received CCRT with or without IC
before were included in the study population. Overall survival (OS) rate,
progression-free survival (PFS) rate, locoregional recurrence-free survival
(LRFS) rate, and distant metastasis-free survival (DMFS) rate were assessed by
the Kaplan-Meier method and a log-rank test. Treatment toxicities were clarified
and compared between two groups. RESULTS: One hundred and thiry of 194 patients
received IC+CCRT. Patients who were younger and with more advanced TNM stage were
more likely to receive IC+CCRT and intensive modulated radiotherapy. The addition
of IC before CCRT failed to improve survival significantly. The matched analysis
identified 43 well-balanced patients in both two groups. With a median follow-up
of 51.5 months, no differences were found between the IC+CCRT group and the CCRT
group in 5-year OS (83.7% vs. 74.6%, p=0.153), PFS (79.2% vs. 73.4%, p=0.355),
LRFS (97.7% vs. 88.2%, p=0.083), and DMFS (81.6% vs. 81.6%, p=0.860). N3 was an
independent prognostic factor predicting poorer OS, PFS, and DMFS. The addition
of IC was associated with increased rates of grade 3 to 4 neutropenia.
CONCLUSION: This study failed to demonstrate that adding IC before CCRT could
provide a significant additional survival benefit for LACANPC patients. Further
investigations are warranted.
PMID- 29334606
TI - The Association of Acquired T790M Mutation with Clinical Characteristics after
Resistance to First-Line Epidermal Growth Factor Receptor Tyrosine Kinase
Inhibitor in Lung Adenocarcinoma.
AB - PURPOSE: The main objective of this study was to investigate the relationship
among the clinical characteristics and the frequency of T790M mutation in
advanced epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma
patients with acquired resistance after firstline EGFR-tyrosine kinase inhibitor
(TKI) treatment. Materials and Methods: We enrolled EGFR-mutant stage IIIB-IV
lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and
evaluated their rebiopsy EGFR mutation status. RESULTS: A total of 205 patients
were enrolled for analysis. The overall T790M mutation rate of rebiopsy was
46.3%. The T790M mutation rates among patients with exon 19 deletion mutation,
exon 21 L858R point mutation, and other mutations were 55.0%, 37.3%, and 27.3%,
respectively. Baseline exon 19 deletion was associated with a significantly
higher frequency of T790M mutation (adjusted odds ratio, 2.14; 95% confidence
interval [CI], 1.20 to 3.83; p=0.010). In the exon 19 deletion subgroup, there
was a greater prevalence of T790M mutation than other exon 19 deletion subtypes
in patients with the Del E746-A750 mutation (61.6% vs. 40.6%; odds ratio, 2.35;
95% CI, 1.01 to 5.49; p=0.049). The progression-free survival (PFS) of first-line
TKI treatment > 11 months was also associated with a higher T790M mutation rate
(54.1% vs. 39.3%; adjusted odds ratio, 1.82; 95% CI, 1.02 to 3.25; p=0.044).
Patients who underwent rebiopsy at metastatic sites had more chance to harbor
T790M mutation (52.6% vs. 33.8%; adjusted odds ratio, 1.97; 95% CI, 1.06 to 3.67;
p=0.032). CONCLUSION: PFS of first-line EGFR-TKI, rebiopsy site, EGFR exon 19
deletion and its subtype Del E746- A750 mutation are associated with the
frequency of T790M mutation.
PMID- 29334607
TI - Geographical Variations and Trends in Major Cancer Incidences throughout Korea
during 1999-2013.
AB - PURPOSE: We aimed to describe the temporal trends and district-level geographical
variations in cancer incidences throughout Korea during 1999-2013. Materials and
Methods: Data were obtained from the Korean National Cancer Incidence Database.
We calculated the age-standardized cumulative cancerincidences according to sex
and geographicalregion (metropolitan cities, provinces, and districts) for three
5-year periods (1999-2003, 2004- 2008, and 2009-2013). Each quintile interval
contained the same number of regions. Disease maps were created to visualize
regional differences in the cancer incidences. RESULTS: Substantial differences
in cancer incidences were observed according to district and cancer type. The
largest variations between geographical regions were found for thyroid cancer
among both men and women. There was little variation in the incidences of
stomach, colorectal, and lung cancer according to geographical region.
Substantially elevated incidences of specific cancers were observed in Jeollanam
do (thyroid); Daejeon (colorectum); Jeollanam-do, Gyeongsangbuk-do, and
Chungcheongbuk-do (lung); Seocho-gu, Gangnam-gu and Seongnam, Bundang-gu (breast
and prostate); Chungcheong and Gyeongsang provinces (stomach); Ulleung-gun and
the southern districts of Gyeongsangnam-do and Jeollanam-do (liver); and along
the Nakdonggang River (gallbladder and biliary tract). CONCLUSION: Mapping
regional cancer incidences in Korea allowed us to compare the results according
to geographical region. Our results may facilitate the development of
infrastructure for systematic cancerincidence monitoring,which could promote the
planning and implementation of region-specific cancer management programs.
PMID- 29334608
TI - Factors Associated with Prolonged Patient-Attributable Delay in the Diagnosis of
Colorectal Cancer.
AB - PURPOSE: The delayed diagnosis of colorectal cancer (CRC) may be attributable to
sociodemographic characteristics, to aspects of tumour histopathology or to the
functioning of the health system. We seek to determine which of these factors
most influences prolonged patient-attributable delay (PPAD) in the diagnosis and
treatment of CRC. Materials and Methods: A prospective, multicentre observational
study was conducted in 22 Spanish hospitals. In total, 1,785 patients were
recruited to the study between 2010 and 2012 and underwent elective or urgent
surgery. PPAD is considered to occur when the time elapsed between a patient
presenting the symptom and him/her seeking attention from the primary care
physician or hospital emergency department exceeds 180 days. A bivariate analysis
was performed to assess differences in variables segmented by tumour location and
patient delay. Multivariate logistic regression analysis was performed on the
outcome variable, PPAD. RESULTS: The rate of PPAD among this population was
12.1%. PPAD was significantly associated with altered bowel rhythm (odds ratio
[OR], 1.36; 95% confidence interval [CI], 1.02 to 1.83) and with adenocarcinoma
histology, in comparison with mucinous adenocarcinoma (OR, 2.03; 95% CI, 1.11 to
3.71). Other sociocultural factors and clinicopathological features were not
independent predictors of PPAD. CONCLUSION: Many patients do not consider altered
bowel rhythm an alarming symptom, warranting a visit to the doctor. PPAD could be
reduced by improving health education, raising awareness of CRC-related symptoms.
PMID- 29334609
TI - Score for the Survival Probability in Metastasis Breast Cancer: A Nomogram-Based
Risk Assessment Model.
AB - PURPOSE: Survival of metastatic breast cancer (MBC) patient remains unknown and
varies greatly from person to person. Thus, we aimed to construct a nomogram to
quantify the survival probability of patients with MBC. Materials and Methods: We
had included 793 MBC patients and calculated trends of case fatality rate by
Kaplan-Meier method and joinpoint regression. Six hundred thirty-four patients
with MBC between January 2004 and July 2011 and 159 patients with MBC between
August 2011 and July 2013 were assigned to training cohort and internal
validation cohort, respectively. We constructed the nomogram based on the results
of univariable and multivariable Cox regression analyses in the training cohort
and validated the nomogram in the validation cohort. Concordance index and
calibration curves were used to assess the effectiveness of nomogram. RESULTS:
Case fatality rate of MBC was increasing (annual percentage change [APC], 21.6;
95% confidence interval [CI], 1.0 to 46.3; p < 0.05) in the first 18 months and
then decreased (APC, -4.5; 95% CI, -8.2 to -0.7; p < 0.05). Metastasis-free
interval, age, metastasis location, and hormone receptor status were independent
prognostic factors and were included in the nomogram, which had a concordance
index of 0.69 in the training cohort and 0.67 in the validation cohort.
Calibration curves indicated good consistency between the two cohorts at 1 and 3
years. CONCLUSION: In conclusion, the fatality risk of MBC was increasing and
reached the summit between 13th and 18th month afterthe detection of MBC. We have
developed and validated a nomogram to predict the 1- and 3-year survival
probability in MBC.
PMID- 29334610
TI - Phase II Study of Dovitinib in Patients with Castration-Resistant Prostate Cancer
(KCSG-GU11-05).
AB - PURPOSE: Fibroblast growth factor (FGF) signals are important in carcinogenesis
and progression of prostate cancer. Dovitinib is an oral, pan-class inhibitor of
vascular endothelial growth factor receptor (VEGFR), platelet-derived growth
factor receptor, and fibroblast growth factor receptor (FGFR). We evaluated the
efficacy and toxicity of dovitinib in men with metastatic castration resistant
prostate cancer (mCRPC). Materials and Methods: This study was a single-arm,
phase II, open-label, multicenter trial of dovitinib 500 mg/day (5-days-on/2-days
off schedule). The primary endpointwas 16-week progression-free survival (PFS).
Secondary endpoints were overall survival (OS), toxicity and prostate-specific
antigen (PSA) response rate. Biomarker analyses for VEGFR2, FGF23, and FGFR2
using multiplex enzyme-linked immunosorbent assay was performed. RESULTS: Forty
four men were accrued from 11 hospitals. Eighty percent were post-docetaxel.
Median PSA was 100 ng/dL, median age was 69, 82% had bone metastases, and 23% had
liver metastases. Median cycles of dovitinibwas 2 (range, 0 to 33). Median PFSwas
3.67 months (95% confidence interval [CI], 1.36 to 5.98) and median OS was 13.70
months (95% CI, 0 to 27.41). Chemotherapy-naive patients had longer PFS (17.90
months; 95% CI, 9.23 to 28.57) compared with docetaxel-treated patients (2.07
months; 95% CI, 1.73 to 2.41; p=0.001) and the patients with high serum VEGFR2
level over median level (7,800 pg/mL) showed longer PFS compared with others
(6.03 months [95% CI, 4.26 to 7.80] vs. 1.97 months [95% CI, 1.79 to 2.15],
p=0.023). Grade 3 related adverse events were seen in 40.9% of patients. Grade 1
2 nausea, diarrhea, fatigue, anorexia, and all grade thrombocytopenia are common.
CONCLUSION: Dovitinib showed modest antitumor activity with manageable toxicities
in men with mCRPC. Especially, patients who were chemo-naive benefitted from
dovitinib.
PMID- 29334611
TI - Understanding Complex Tribofilms by Means of H3BO3-B2O3 Model Glasses.
AB - The discovery of the spontaneous reaction of boric oxides with moisture in the
air to form lubricious H3BO3 films has led to great interest in the tribology of
boron compounds in general. Despite this, a study of the growth kinetics of H3BO3
on a B2O3 substrate under controlled relative humidity (RH) has not yet been
reported in the literature. Here, we describe the tribological properties of
H3BO3-B2O3 glass systems after aging under controlled RH over different lengths
of time. A series of tribological tests has been performed applying a normal load
of 15 N, at both room temperature and 100 degrees C in YUBASE 4 oil. In
addition, the cause of H3BO3 film failure under high-pressure and high
temperature conditions has been studied to find out whether the temperature, the
tribostress, or both influence the removal of the lubricious film from the
contact points. The following techniques were exploited: confocal Raman
spectroscopy to characterize the structure and chemical nature of the glass
systems, environmental scanning electron microscopy to examine the morphology of
the H3BO3 films developed, atomic force microscopy to monitor changes in
roughness as a consequence of the air exposure, focused-ion-beam scanning
electron microscopy to measure the average thickness of the H3BO3 films grown
over various times on B2O3 glass substrates and to reveal the morphology of the
sample in the vertical section, tribological tests to shed light on the system's
lubricating properties, and finally small-area X-ray photoelectron spectroscopy
to investigate the composition of the transfer film formed on the steel ball
while tribotesting.
PMID- 29334612
TI - TEMPO-Oxidized Bacterial Cellulose Pellicle with Silver Nanoparticles for Wound
Dressing.
AB - Biocompatible bacterial cellulose pellicle (BCP) is a candidate for biomedical
material such as wound dressing. However, due to lack of antibacterial activity,
to grant BCP with the property is crucial for its biomedical application. In the
present study, BCP was modified by 2,2,6,6-tetramethylpiperidine-1-oxyl radical
(TEMPO)-mediated oxidation using TEMPO/NaClO/NaBr system at pH 10 to form TEMPO
oxidized BCP (TOBCP) with anionic C6 carboxylate groups. The TOBCP was
subsequently ion-exchanged in AgNO3 solution and silver nanoparticles (AgNP) with
diameter of ~16.5 nm were in situ synthesized on TOBC nanofiber surfaces by
thermal reduction without using a reducing agent. Field emission scanning
electron microscopy, X-ray diffraction, X-ray photoelectron spectra, Fourier
transform infrared spectroscopy, and thermogravimetric analysis were carried out
to confirm morphology and structure of the pellicles with AgNP. The AgNP
continuously released Ag+ with a rate of 12.2%/day at 37 degrees C in 3 days.
The TOBCP/AgNP exhibited high biocompatibility according to the result of in
vitro cytotoxicity test (cell viability >95% after 48 h of incubation) and showed
significant antibacterial activities of 100% and 99.2% against E. coli and S.
aureus, respectively. Hence, the highly biocompatible and highly antibacterial
TOBCP/AgNP prepared in the present study is a promising candidate for wound
dressing.
PMID- 29334613
TI - Reduced miR-144-3p expression in serum and bone mediates osteoporosis
pathogenesis by targeting RANK.
AB - Osteoblasts and osteoclasts are responsible for the formation and resorption of
bone, respectively. An imbalance between these two processes results in a disease
called osteoporosis, in which a decreased level of bone strength increases the
risk of a bone fracture. MicroRNAs (miRNAs) are small non-coding RNA molecules of
18-25 nucleotides that have been previously shown to control bone metabolism by
regulating osteoblast and osteoclast differentiation. In this study, we detected
the expression pattern of 10 miRNAs in serum samples from patients with
osteoporosis, and identified the altered expression of 6 miRNAs by comparison
with patients without osteoporosis. We selected miR-144-3p for further
investigation, and showed that it regulates osteoclastogenesis by targeting RANK,
and that it is conserved amongst vertebrates. Disrupted expression of miR-144-3p
in CD14+ peripheral blood mononuclear cells changed TRAP activity and the
osteoclast-specific genes TRAP, cathepsin K (CTSK), and NFATC. TRAP staining, CCK
8, and flow cytometry analyses revealed that miR-144-3p also affects osteoclast
formation, proliferation, and apoptosis. Together, these results indicate that
miR-144-3p critically mediates bone homeostasis, and thus, represents a promising
novel therapeutic candidate for the treatment of this disease.
PMID- 29334614
TI - Perceptions of exercise screening among older adults.
AB - Prephysical activity screening is important for older adults' participating in
physical activity. Unfortunately, many older adults face barriers to exercise
participation and thus, may not complete proper physical activity screening. The
purpose of this project was to conduct a thematic analysis of perceptions and
experiences of community-dwelling older adults regarding prephysical activity
screening (i.e., Get Active Questionnaire (GAQ) and a standardized exercise
stress test). A convenience sample of adults (male n = 58, female n = 54) aged 75
+/- 7 years living in the City of London, Ontario, Canada, was used. Participants
completed a treadmill stress test and the GAQ at a research laboratory for
community-based referrals. One week later, participants completed the GAQ again
and were asked questions by a research assistant about their perceptions of the
screening process. Thematic analysis of the responses was conducted. The results
indicated that older adults view physical activity screening as acceptable, but
not always necessary. Also, the experiences expressed by this sample of older
adults indicated that physical activity screening can contribute to continued
confidence (through reassurance) and can contribute to increased motivation
(through yearly fitness results) in exercise participation. In conclusion, older
adults may perceive screening as supportive in exercise adoption, if screening is
simple, convenient, and supports older adults' motivation and confidence to
exercise.
PMID- 29334615
TI - Hemodynamic and metabolic responses to self-paced and ramp-graded exercise
testing protocols.
AB - Recent examinations have shown lower maximal oxygen consumption during
traditional ramp (RAMP) compared with self-paced (SPV) graded exercise testing
(GXT) attributed to differences in cardiac output. The current study examined the
differences in hemodynamic and metabolic responses between RAMP and SPV during
treadmill exercise. Sixteen recreationally trained men (aged23.7 +/- 3.0 years)
completed 2 separate treadmill GXT protocols. SPV consisted of five 2-min stages
(10 min total) of increasing speed clamped by the Borg RPE6-20 scale. RAMP
increased speed by 0.16 km/h every 15 s until volitional exhaustion. All testing
was performed at 3% incline. Oxygen consumption was measured via indirect
calorimetry; hemodynamic function was measured via thoracic impedance and blood
lactate (BLa-) was measured via portable lactate analyzer. Differences between
SPV and RAMP protocols were analyzed as group means by using paired-samples t
tests (R Core Team 2017). Maximal values for SPV and RAMP were similar (p > 0.05)
for oxygen uptake (47.1 +/- 3.4 vs. 47.4 +/- 3.4 mL.kg-1.min-1), heart rate (198
+/- 5 vs. 200 +/- 6 beats.min-1), ventilation (158.8 +/- 20.7 vs. 159.3 +/- 19.0
L.min-1), cardiac output (26.9 +/- 5.5 vs. 27.9 +/- 4.2 L.min-1), stroke volume
(SV) (145.9 +/- 29.2 vs. 149.8 +/- 25.3 mL.beat-1), arteriovenous oxygen
difference (18.5 +/- 3.1 vs. 19.7 +/- 3.1 mL.dL-1), ventilatory threshold (VT)
(78.2 +/- 7.2 vs. 79.0% +/- 7.6%), and peak BLa- (11.7 +/- 2.3 vs. 11.5 +/- 2.4
mmol.L-1), respectively. In conclusion, SPV elicits similar maximal hemodynamic
responses in comparison to RAMP; however, SV kinetics exhibited unique
characteristics based on protocol. These results support SPV as a feasible GXT
protocol to identify useful fitness parameters (maximal oxygen uptake, oxygen
uptake kinetics, and VT).
PMID- 29334616
TI - Preoperative Breast Magnetic Resonance Imaging Use by Breast Density and Family
History of Breast Cancer.
AB - BACKGROUND: Use of preoperative breast magnetic resonance imaging (MRI) among
women with a new breast cancer has increased over the past decade. MRI use is
more frequent in younger women and those with lobular carcinoma, but associations
with breast density and family history of breast cancer are unknown. MATERIALS
AND METHODS: Data for 3075 women ages >65 years with stage 0-III breast cancer
who underwent breast conserving surgery or mastectomy from 2005 to 2010 in the
Breast Cancer Surveillance Consortium were linked to administrative claims data
to assess associations of preoperative MRI use with mammographic breast density
and first-degree family history of breast cancer. Multivariable logistic
regression estimated adjusted odds ratios (OR) and 95% confidence intervals (95%
CI) for the association of MRI use with breast density and family history,
adjusting for woman and tumor characteristics. RESULTS: Overall, preoperative MRI
use was 16.4%. The proportion of women receiving breast MRI was similar by breast
density (17.6% dense, 16.9% nondense) and family history (17.1% with family
history, 16.5% without family history). After adjusting for potential
confounders, we found no difference in preoperative MRI use by breast density (OR
= 0.95 for dense vs. nondense, 95% CI: 0.73-1.22) or family history (OR = 0.99
for family history vs. none, 95% CI: 0.73-1.32). CONCLUSIONS: Among women aged
>65 years with breast cancer, having dense breasts or a first-degree relative
with breast cancer was not associated with greater preoperative MRI use. This
utilization is in keeping with lack of evidence that MRI has higher yield of
malignancy in these subgroups.
PMID- 29334617
TI - Chains of risk for alcohol use disorder: Mediators of exposure to neighborhood
deprivation in early and middle childhood.
AB - Our goal was to test a cascade model to identify developmental pathways, or
chains of risk, from neighborhood deprivation in childhood to alcohol use
disorder (AUD) in young adulthood. Using Swedish general population data, we
examined whether exposure to neighborhood deprivation during early and middle
childhood was associated with indicators of social functioning in adolescence and
emerging adulthood, and whether these were predictive of AUD. Structural equation
models showed exposure to neighborhood deprivation was associated with lower
school achievement during adolescence, poor social functioning during emerging
adulthood, and the development of AUD for both males and females. Understanding
longitudinal pathways from early exposure to adverse environments to later AUD
can inform prevention and intervention efforts.
PMID- 29334619
TI - Comparisons between a new point kernel-based scheme and the infinite plane source
assumption method for radiation calculation of deposited airborne radionuclides
from nuclear power plants.
AB - Radiation from the deposited radionuclides is indispensable information for
environmental impact assessment of nuclear power plants and emergency management
during nuclear accidents. Ground shine estimation is related to multiple physical
processes, including atmospheric dispersion, deposition, soil and air radiation
shielding. It still remains unclear that whether the normally adopted "infinite
plane" source assumption for the ground shine calculation is accurate enough,
especially for the area with highly heterogeneous deposition distribution near
the release point. In this study, a new ground shine calculation scheme, which
accounts for both the spatial deposition distribution and the properties of air
and soil layers, is developed based on point kernel method. Two sets of "detector
centered" grids are proposed and optimized for both the deposition and radiation
calculations to better simulate the results measured by the detectors, which will
be beneficial for the applications such as source term estimation. The evaluation
against the available data of Monte Carlo methods in the literature indicates
that the errors of the new scheme are within 5% for the key radionuclides in
nuclear accidents. The comparisons between the new scheme and "infinite plane"
assumption indicate that the assumption is tenable (relative errors within 20%)
for the area located 1 km away from the release source. Within 1 km range, the
assumption mainly causes errors for wet deposition and the errors are independent
of rain intensities. The results suggest that the new scheme should be adopted if
the detectors are within 1 km from the source under the stable atmosphere
(classes E and F), or the detectors are within 500 m under slightly unstable
(class C) or neutral (class D) atmosphere. Otherwise, the infinite plane
assumption is reasonable since the relative errors induced by this assumption are
within 20%. The results here are only based on theoretical investigations. They
should be further thoroughly evaluated with real measurements in the future.
PMID- 29334618
TI - Exploring masculinities, sexual health and wellbeing across areas of high
deprivation in Scotland: The depth of the challenge to improve understandings and
practices.
AB - Within and across areas of high deprivation, we explored constructions of
masculinity in relation to sexual health and wellbeing, in what we believe to be
the first UK study to take this approach. Our sample of 116 heterosexual men and
women age 18-40 years took part in individual semi-structured interviews (n = 35)
and focus group discussions (n = 18), across areas in Scotland. Drawing on a
socio-ecological framework, findings revealed experience in places matter, with
gender practices rooted in a domestically violent milieu, where localised, socio
cultural influences offered limited opportunities for more egalitarian
performances of masculinity. We discuss the depths of the challenge in
transforming masculinities in relation to sexual health and wellbeing in such
communities.
PMID- 29334620
TI - Evaluation of abundance of artificial radionuclides in food products in South
Korea and sources.
AB - Food samples are collected nationwide from January 2016 to February 2017 and
their contents of artificial radionuclides are measured to address the growing
concerns regarding the radioactive contamination of food products in Korea.
Specifically, 900 food samples are collected for this study and their contents of
representative artificial radionuclides 134Cs, 137Cs, 239,240Pu, and 90Sr are
analyzed. The analysis shows that the activity concentrations of 137Cs in fish
range from minimum detectable activity (MDA) to 340 mBq/kg of fresh weight. The
concentration factor (CF) determined for 137Cs as a measure of its
bioavailability is calculated to be ca. 74 and found to be very similar to that
(100) recommended by the International Atomic Energy Agency. With an MDA of
<0.221 mBq/kg, the results reveal that 239,240Pu values in fish are below the
MDA. The activity concentrations of 137Cs and 90Sr are lower than the MDA in both
shellfish and seaweed, while the activity concentrations of 239,240Pu in
shellfish range from 0.26 to 2.18 mBq/kg, and for seaweed samples range from 2.07
to 3.38 mBq/kg. The atom ratios of 240Pu/239Pu in shellfish caught at the Korean
coast vary from 0.209 to 0.237, with a mean of 0.227. The higher 240Pu/239Pu atom
ratio determined in shellfish is thought to be caused by the plutonium
transported from the Pacific Proving Grounds rather than other sources such as
the Fukushima nuclear power plant accident. The activity concentrations of 137Cs
in mushrooms are found to vary from 1.0 to 21.4 Bq/kg, with the highest
concentrations observed in the Oak (shiitake) and Sarcodon asparatus. 134Cs is
detected in three mushroom specimens collected from Jeju Island and about 3-3.6%
of 137Cs present in the wild mushrooms native to the Jeju Island are introduced
as a result of the Fukushima nuclear plant accident. The annual effective doses
of 137Cs received through consumption of mushrooms and fish are 2.0 * 10-4 mSv yr
1 and 3.9 * 10-5 mSv yr-1, and those values are negligible compared to the annual
effective doses limit of 1 mSv yr-1.
PMID- 29334621
TI - Taurine as a green bio-organic catalyst for the preparation of bio-active
barbituric and thiobarbituric acid derivatives in water media.
AB - Taurine, a beta-amino acid that is abundantly available in the tissues of human
and animals, is efficiently used as a green bio-organic catalyst in the
preparation of some of the biologically active barbituric and thiobarbituric acid
derivatives. In the presence of taurine, 5-Arylidene (thio) barbituric acid
derivatives were prepared via Knovenagel reaction between aldehydes and
(thio)barbituric acid. Using this reagent also pyrano[2,3-d]pyrimidinone(thione)
derivatives were synthesized through a three-component reaction between
aldehydes, (thio)barbituric and malononitrile. Both reactions are performed in
water with good to excellent yields during acceptable reaction times. No organic
solvent was used during reaction or separation steps and no extra-purification
was exerted. Meanwhile, reusability of taurine was easy and noticeably high.
PMID- 29334622
TI - Pyridazinone hybrids: Design, synthesis and evaluation as potential
anticonvulsant agents.
AB - A series of new hybrid benzothiazole containing pyridazinones derivatives were
designed and synthesized fulfilling all the pharmacophoric requirements essential
for the anticonvulsant activity. In-silico and in vitro studies revealed that
some of these hybrid derivatives demonstrated admirable GABA AT inhibitory
activity. An attempt has also been made to validate the results of in vitro GABA
AT inhibition of the most potent compound SPS-5F (IC50 9.10 MUM) through in vivo
anticonvulsant screening. Compound SPS-5F administration significantly increases
the whole brain GABA level, might be through the inhibition of GABA AT enzyme.
PMID- 29334623
TI - An alternative carrier solvent for fingermark enhancement reagents.
AB - Solstice(r) Performance Fluid (PF), trans-1-chloro-3,3,3-trifluoropropene, is
presented as an alternative to HFE7100, methoxy-nonafluorobutane, as a carrier
solvent in a number of chemical formulations used for the visualisation of latent
fingermarks. The supply of HFE7100 may be at risk due to a recent European Union
regulation to control global warming. Laboratory trials using split depletions
and a pseudo-operational trial of 1000 porous samples have shown that Solstice(r)
PF is a viable alternative to HFE7100 for the chemical formulations of ninhydrin
and 1,2-indanedione. Other preliminary trials have also indicated that
Solstice(r) PF can be used as a carrier solvent for the zinc toning of marks
found using ninhydrin as well as the alpha-naphtholflavone fixative solution for
iodine developed marks. Results from the pseudo-operational trial demonstrate
that the number of marks detected by ninhydrin and 1,2-indanedione formulations
for each carrier solvent is comparable. When compared to HFE7100, advantages of
Solstice(r) PF include a very low global warming potential and atmospheric
lifetime in addition to a higher wetting index and lower costs. This study also
provides a validation study that supports the potential replacement of DFO with
1,2-indanedione.
PMID- 29334624
TI - Adequate vitamin D3 skin synthesis versus erythema risk in the Northern
Hemisphere midlatitudes.
AB - Health-optimum-exposure index (HOEI) is proposed to assess if the prescribed
amount of vitamin D3 (target value) could be synthesized in the human skin
without erythema appearance. It is defined as the ratio between the vitamin D3
quantity received during the maximum allowed outdoor exposure without erythema
risk and the target value. Sunbathing is safe for HOEI>1 and 1/HOEI represents a
part of minimal erythema dose (MED) necessary to obtain the target value. We
examine the following targets: a vitamin D3 quantity equivalent to 1000 IU
vitamin D3 taken orally, and an optimal vitamin D3 quantity defined by Krzyscin
et al. (2016). The biologically weighted (previtamin D3 and erythemal) doses from
the Northern Hemisphere midlatitudinal stations are analyzed to find HOEI
dependence on personal and meteorological factors. HOEI depends mostly on the
exposed skin area, person's age, and sun elevation at noon but not on the
Fitzpatrick skin phototype. We found that only young adults (<21 yr) could safely
obtain vitamin D3 quantity, which is equivalent to 1000 IU taken orally, almost
throughout the whole year. Duration of such exposures appears <1 h only in the
warm subperiods of the year (April-September) for a person with minimal erythema
dose of 330 J m-2. Exposing larger part of the body (~30%) enables the oldest
persons (>59 yr) to reach 1000 IU target during warm days in spring and summer.
The optimal daily vitamin D3 quantity could only be synthesized only by young
adults for about 40-60% of days in the May-August period if they expose at least
1/3 part of their body surface area. Vitamin D3 supplementation seems to be
necessary over the whole year for the oldest persons with daily dosage of ~2000
IU but reduced to ~1000 IU in summer for sunseekers exposing significant part of
the body.
PMID- 29334625
TI - Light quality affects flavonoid production and related gene expression in
Cyclocarya paliurus.
AB - Understanding the responses of plant growth and secondary metabolites to
differential light conditions is very important to optimize cultivation
conditions of medicinal woody plants. As a highly valued and multiple function
tree species, Cyclocarya paliurus is planted and managed for timber production
and medical use. In this study, LED-based light including white light (WL), blue
light (BL), red light (RL), and green light (GL) were used to affect leaf biomass
production, flavonoid accumulation and related gene expression of one-year C.
paliurus seedlings in controlled environments. After the treatments of 60 days,
the highest leaf biomass appeared in the treatment of WL, while the lowest leaf
biomass was found under GL. Compared to WL, the total flavonoid contents of C.
paliurus leaves were significantly higher in BL, RL, and GL, but the highest
values of selected flavonoids (kaempferol, isoquercitrin and quercetin) were
observed under BL. Furthermore, the greatest yields of total and selected
flavonoids in C. paliurus leaves per seedling were also achieved under BL,
indicating that blue light was effective for inducing the production of
flavonoids in C. paliurus leaves. Pearson's correlation analysis showed that
there were significantly positive correlations between leaf flavonoid content and
relative gene expression of key enzymes (phenylalanine ammonia lyase, PAL; 4
coumaroyl CoA-ligase, 4CL; and chalcone synthase, CHS) in the upstream, which
converting phenylalanine into the flavonoid skeleton of tetrahydroxy chalcone. It
is concluded that manipulating light quality may be potential mean to achieve the
highest yields of flavonoids in C. paliurus cultivation, however this needs to be
further verified by more field trials.
PMID- 29334626
TI - Parenting predicts Strange Situation cortisol reactivity among children adopted
internationally.
AB - The functioning of the hypothalamic pituitary adrenal (HPA) axis can be altered
by adverse early experiences. Recent studies indicate that children who were
adopted internationally after experiencing early institutional rearing and
unstable caregiving exhibit blunted HPA reactivity to stressful situations. The
present study examined whether caregiving experiences post-adoption further
modulate children's HPA responses to stress. Parental sensitivity during
naturalistic parent-child play interactions was assessed for 66 children (M age =
17.3 months, SD = 4.6) within a year of being adopted internationally.
Approximately 8 months later, children's salivary cortisol levels were measured
immediately before as well as 15 and 30 min after a series of brief separations
from the mother in an unfamiliar laboratory setting. Latent growth curve modeling
indicated that experiencing more parental sensitivity predicted increased
cortisol reactivity to the stressor. Although half the families received an
intervention designed to improve parental sensitivity, the intervention did not
significantly alter children's cortisol outcomes. These findings suggest that
post-adoption parental sensitivity may help normalize the HPA response to stress
among children adopted internationally.
PMID- 29334627
TI - Testosterone, DHEA and DHEA-S in patients with schizophrenia: A systematic review
and meta-analysis.
AB - Neuroactive steroids, including testosterone, dehydroepiandrosterone (DHEA) and
its sulfate (DHEA-S) might play an important role in the pathophysiology of
schizophrenia. Therefore, we performed a systematic review and meta-analysis of
studies comparing the levels of testosterone, DHEA and DHEA-S in patients with
schizophrenia and healthy controls. We searched electronic databases from their
inception until Oct 29, 2017. Effect size (ES) estimates were calculated as
Hedges' g. Data analysis was performed using random-effects models. Our analysis
included 34 eligible studies, representing 1742 patients and 1604 controls. Main
analysis revealed elevated DHEA-S levels in the whole group of patients (ES =
0.75, 95%CI: 0.23-1.28, p = 0.005). In subgroup analyses, patients with first
episode psychosis (FEP) had significantly higher levels of free testosterone (ES
= 1.21, 95%CI: 0.30-2.12, p = 0.009) and DHEA-S (ES = 1.19, 95%CI: 0.66-1.71, p <
0.001). Acutely relapsed schizophrenia patients presented significantly higher
levels of total testosterone (ES = 0.50, 95%CI: 0.21-0.70, p < 0.001). Total
testosterone levels were also elevated in stable multi-episode schizophrenia
(sMES) females (ES = 0.56, 95%CI: 0.33-0.80, p < 0.001) and reduced in sMES males
(ES = -0.62, 95%CI: -1.07 to 0.18, p = 0.006). Increased levels of biologically
active, free testosterone and DHEA-S in FEP suggest that these alterations might
appear as a response to stress that becomes blunted during subsequent
exacerbations of schizophrenia. Differential changes in total testosterone levels
in male and female sMES patients might represent medication effects related to
prolactin-releasing effects of antipsychotics.
PMID- 29334628
TI - Production and characterization of human induced pluripotent stem cells (iPSCs)
from Joubert Syndrome: CSSi001-A (2850).
AB - Joubert Syndrome (JS) is a rare autosomal recessive or X-linked condition
characterized by a peculiar cerebellar malformation, known as the molar tooth
sign (MTS), associated with other neurological phenotypes and multiorgan
involvement. JS is a ciliopathy, a spectrum of disorders whose causative genes
encode proteins involved in the primary cilium apparatus. In order to elucidate
ciliopathy-associated molecular mechanisms, human induced pluripotent stem cells
(hiPSCs) were derived from a patient affected by JS carrying a homozygous
missense mutation in the AHI1 gene (p.H896R) that encodes a protein named
Jouberin.
PMID- 29334629
TI - Generation of a human induced pluripotent stem cell line (CSC-42) from a patient
with sporadic form of Parkinson's disease.
AB - Skin fibroblasts were collected from a 44-year-old patient with sporadic case of
Parkinson's disease (PD). The non-integrating Sendai virus vector encoding
OCT3/4, SOX2, c-MYC and KLF4 was used to reprogram fibroblasts into induced
pluripotent stem cells (iPSCs). Generated iPSCs had normal karyotypes, expressed
common stem cell markers, and were capable of differentiating into all three germ
layers. Generated line could be used for PD modeling to understand the mechanisms
that influence the disorder.
PMID- 29334630
TI - Generation of an integration-free induced pluripotent stem cell line (CSC-43)
from a patient with sporadic Parkinson's disease.
AB - An induced pluripotent stem cell (iPSC) line was generated from a 36-year-old
patient with sporadic Parkinson's disease (PD). Skin fibroblasts were
reprogrammed using the non-integrating Sendai virus technology to deliver OCT3/4,
SOX2, c-MYC and KLF4 factors. The generated cell line (CSC-43) exhibits
expression of common pluripotency markers, in vitro differentiation into three
germ layers and normal karyotype. This iPSC line can be used to study the
mechanisms underlying the development of PD.
PMID- 29334631
TI - Acceptability of intervention materials to decrease risk for alcohol and
medication interactions among older adults.
AB - BACKGROUND: The majority of older adults take prescription or over-the-counter
medications and about half consume alcohol regularly. Despite high risk for
alcohol medication interactions (AMI), few community-level interventions exist to
prevent AMI. The current study assessed the acceptability of educational
materials created for use in a brief intervention to prevent AMI among older
adults. METHODS: Older adults from two senior centers reviewed intervention
materials (poster, patient and pharmacist brochures, and public service
announcement) and participated in a pre and post-test to provide feedback and to
assess changes in AMI-related awareness and intentions. RESULTS: Post-test data
showed positive feedback and an increase in participant understanding of AMI
prevention, with statistically significant changes in perceived importance of
messaging surrounding risky alcohol use and potential consequences of AMI.
DISCUSSION: The intervention materials were positively received, and participant
feedback indicated that the collective presentation of all the materials was the
most preferred tool for educating the community. With positive trends in
awareness and knowledge, intervention effectiveness needs to be further evaluated
in future large-scale studies. LESSONS LEARNED: This study provides health
education specialists with tools to prevent alcohol and medication interactions
among older adults.
PMID- 29334632
TI - Capillary electrophoresis-mass spectrometry for targeted and untargeted analysis
of the sub-5 kDa urine metabolome of patients with prostate or bladder cancer: A
feasibility study.
AB - Targeted and untargeted analyses of the sub-5 kDa urine metabolome of
genitourinary cancer patients (prostate and/or bladder) were performed without
chemical derivatization using capillary electrophoresis-electrospray ionization
mass spectrometry (CE-ESI-MS). For targeted analysis, endogenous levels of
sarcosine and 5 other amino acid metabolites implicated in the progression of
prostate cancer were quantified in four patients and in a pooled urine sample
from healthy volunteers. An untargeted analysis (m/z 50 to 850) of patient urine
was performed using the same CE-ESI-MS system identifying over 400 distinct
molecular features per patient. All patient urine samples were collected at
prostatectomy/cystectomy via catheter. Patient urine samples were filtered by
centrifugation, with endogenous sarcosine enriched by solid-phase extraction, and
the processed samples loaded onto CE-ESI-MS for analysis. Diagnostic information,
digital pathological slides, and tissue samples were collected and stored in a
comprehensive biobanking database. The introduction of urine sample collection
into the surgery workflow was facile and is a promising strategy for addressing
the translational research challenge of moving smoothly from "chromatogram to
nomogram".
PMID- 29334633
TI - Fluorous-assisted metal chelate affinity extraction for nucleotides followed by
HILIC-MS/MS analysis.
AB - We herein developed a selective method for the determination of nucleotides by
fluorous-assisted metal chelate affinity extraction followed by hydrophilic
interaction liquid chromatography (HILIC) combined with tandem mass spectrometric
(MS/MS) analysis. In this study, the nucleotides were selectively chelated by
Fe(III)-immobilized perfluoroalkyliminodiacetic acid, and the resulting chelates
were subsequently extracted into a fluorous solvent. The nucleotides present in
the fluorous solvent were then back-extracted into a non-fluorous solution, such
as a solution of ammonia in aqueous acetonitrile. The resulting non-fluorous
solution containing the nucleotides was then directly injected into an amide-type
HILIC column using a mixture of acetonitrile and aqueous ammonium bicarbonate as
the mobile phase for gradient elution, and the nucleotides were detected using
the negative electrospray ionization MS/MS mode. In this method, the extraction
recoveries of the nucleotides ranged from 43.2 to 94.7% within a relative
standard deviation of 17%. This method enabled the determination of intracellular
concentrations of nucleotides.
PMID- 29334634
TI - Equine in vivo-derived metabolites of the SARM LGD-4033 and comparison with human
and fungal metabolites.
AB - LGD-4033 has been found in human doping control samples and has the potential for
illicit use in racehorses as well. It belongs to the pharmacological class of
selective androgen receptor modulators (SARMs) and can stimulate muscle growth,
much like anabolic steroids. However, SARMs have shown superior side effect
profiles compared to anabolic steroids, which arguably makes them attractive for
use by individuals seeking an unfair advantage over their competitors. The
purpose of this study was to investigate the metabolites formed from LGD-4033 in
the horse in order to find suitable analytical targets for doping controls. LGD
4033 was administered to three horses after which plasma and urine samples were
collected and analyzed for metabolites using ultra high performance liquid
chromatography coupled to a high resolution mass spectrometer. In horse urine,
eight metabolites, both phase I and phase II, were observed most of which had not
been described in other metabolic systems. Six of these were also detected in
plasma. The parent compound was detected in plasma, but not in non-hydrolyzed
urine. The longest detection times were observed for unchanged LGD-4033 in plasma
and in urine hydrolyzed with beta-glucuronidase and is thus suggested as the
analytical target for doping control in the horse. The metabolite profile
determined in the horse samples was also compared to those of human urine and
fungal incubate from Cunninghamella elegans. The main human metabolite,
dihydroxylated LGD-4033, was detected in the horse samples and was also produced
by the fungus. However, it was a not a major metabolite for horse and fungus,
which highlights the importance of performing metabolism studies in the species
of interest.
PMID- 29334635
TI - The effect of altitude and climate on the suicide rates in Turkey.
AB - Suicide is one of the most important public health problems. There was an
association between suicide and several factors such as psychiatric diseases and
psychological characteristics, somatic illness, cultural, socioeconomic,
familial, occupational and individual risk factors. Also, high altitude and
climatic factors including high temperature, cloudiness, more sunshine and low
rainfalls were defined as some of these risk factors in the literature. In this
study, we aimed to investigate correlation between suicide rates and altitudes of
all cities in Turkey and between suicide rates and climatic factors including
Rainfall Activity Index, Winter Mean Temperatures, Summer Mean Temperatures and
Temperature Difference between January and July previously defined by several
authors in the broad series in Turkey. In Turkey, 29865 suicidal deaths occurred
in 10 years period between 2006 and 2015. Of them, 21020 (70.4%) were males and
8845 (29.6%) were females. In this study, we found that high altitude above 1500
m, winter median temperature lower than -10 degrees C and hard temperature
changes above 25 degrees C between winter and summer of settlements were
important factors that affected on female suicide rates appropriate to knowledge
which defined in previous studies. In conclusion, we suggested that the
associations among suicide rates with altitudes and climate should be studied in
wider series obtained from different countries for reaching more reliable
results.
PMID- 29334636
TI - Impact of demographic factors on the antidepressant effect: A patient-level data
analysis from depression trials submitted to the Pharmaceuticals and Medical
Devices Agency in Japan.
AB - A substantial and variable placebo response can cause unreliable findings in
clinical trials designed to demonstrate the efficacy of antidepressants, and the
high rate of failed trials represents a major obstacle in the development of new
drugs for major depressive disorder (MDD). However, the influence of demographic
and symptom factors on the antidepressant effect remains to be established. The
purpose of this study was to estimate the magnitude of this influence. A patient
level meta-analysis of data from double-blind, randomized, placebo-controlled
trials involving the use of antidepressants for adults with MDD was performed.
Data from five confirmatory trials evaluating the efficacy of four
antidepressants that were submitted to the Pharmaceuticals and Medical Devices
Agency (PMDA) to support new drug applications were pooled (n = 1898). The change
in the total score of 17-item Hamilton Depression Rating Scale (HDRS17) was the
primary outcome of interest in our analysis. The changes in the total HDRS17
score in both the antidepressant medication group (ADM) and the placebo group
(PBO) increased in relation to baseline symptom severity. Among older patients
and those with a history of prior treatment with antidepressants, the changes in
the total HDRS17 score decreased in ADM and remained static in PBO. There were no
notable clinical symptoms that influenced the change in the total HDRS17 score.
Baseline symptom severity, participant age and a history of previous treatment
with antidepressants were suggested as moderators of the antidepressant effect.
The drug-placebo difference in the estimated changes as a function of baseline
symptom severity varied depending on the regression models used, and further
studies are required to investigate appropriate models.
PMID- 29334637
TI - Contamination characteristics and source apportionment of heavy metals in topsoil
from an area in Xi'an city, China.
AB - As soil-extractable elements potentially pose ecological and health risks,
identifying their contamination characteristics and sources is crucial.
Therefore, to understand topsoil trace elements in the urban ring zone from the
Second Ring Road to the Third Ring of Xi'an city in China, we determined the
concentrations of Zn, Co, V, As, Cu, Mn, Ba, Ni and Pb, and analyzed the sources
of the contamination. The results showed that the individual pollution indices of
Pb, Co, Cu, Zn, Ba, Ni, Mn, As, and V were 1.79, 1.48, 1.41, 1.33, 1.20, 1.07,
1.04, 0.99, and 0.99, respectively. Evaluation with the aid of the pollution load
index (PLI) indicated slight soil contamination by these elements in the study
area. Using the positive matrix factorization (PMF) method, we identified four
sources of contamination, namely (1) a natural source, (2) traffic emission
source, (3) industrial emission source, and (4) mixed source. PMF is an effective
tool for source apportionment of heavy metals in topsoil. The contribution rates
of the natural source, traffic source, mixed source, and industrial source to the
heavy metal contamination were specified as 25.04%, 24.71%, 24.99%, and 25.26%,
respectively. Considering the above, any attempt to reduce the soil environmental
cost of urban development, has to take into account the heavy metal contamination
of the topsoil from industries, traffic, and other activities.
PMID- 29334638
TI - The effectiveness of physical exercise on cognitive and psychological outcomes in
individuals with mild cognitive impairment: A systematic review and meta
analysis.
AB - OBJECTIVE: Individuals with mild cognitive impairment (MCI) are at high risk for
developing dementia. Physical exercise is a promising intervention for cognitive
decline. Systematic reviews regarding the effects of physical exercise on
cognitive and psychological outcomes among MCI patients are limited, and a
systematic review exploring the effects of exercise modalities on the results has
not been conducted. This study evaluated the effects of physical exercise on
cognitive and psychological outcomes for MCI patients and attempted to identify
which specific modality of exercise is more effective. DESIGN: Systematic review
and meta-analysis. DATA SOURCES: A systematic search of Medline, CINAHL, EMBASE,
PsycINFO, SPORTDiscus, and the China National Knowledge Infrastructure was
performed. REVIEW METHODS: Two reviewers independently assessed the study quality
using the Effective Public Health Practice Project Quality Assessment Tool. Meta
analysis was conducted when data were available, with further subgroup analyses
for exercise types. A series of sensitivity analyses were conducted to explore
the influence of study quality and control types on the primary outcome. A
narrative analysis was performed when statistical synthesis was inappropriate.
RESULTS: Eleven studies met the inclusion criteria. The exercise interventions
can be classified into three types: (a) aerobic exercise, (b) resistance
exercise, and (c) multi-modal exercise. Results showed that physical exercise had
beneficial effects for global cognition [standard mean difference (SMD) = 0.30,
95% confidence interval (CI): 0.10-0.49, p = 0.002]. Further subgroup analysis
demonstrated that aerobic exercise programmes are consistently associated with
medium effect size (SMD: 0.54-0.58). However, the effects of physical exercise on
domain-specific cognitive function and psychological outcomes in MCI patients
remain inconclusive. Results of sensitivity analysis indicated that types of
control exert influence on the outcomes. CONCLUSIONS: Physical exercise, aerobic
exercise in particular, benefits global cognition in MCI patients. The evidence
of physical exercise on domain-specific cognitive function and psychological
outcomes remains unclear, more trials with rigorous study design are necessary to
provide the evidence.
PMID- 29334639
TI - Vestibular schwannoma and hearing preservation: Usefulness of level specific CE
Chirp ABR monitoring. A retrospective study on 25 cases with preoperative
socially useful hearing.
AB - BACKGROUND AND OBJECTIVES: Decision-making regarding the therapy of vestibular
schwannoma (VS) changed over the last decades, during which curative microsurgery
has been promoted. Goals of VS microsurgery are: extensive resection, facial
nerve (FN) preservation and, in selected cases, hearing preservation (HP). The
aim of this study is to evaluate postoperative HP with reference to tumor size in
patients operated on with Level Specific (LS)-CE-Chirp(r) ABR monitoring.
PATIENTS AND METHODS: Twentyfive consecutive patients with socially useful
hearing (SUH) underwent VS microneurosurgery by retrosigmoid (RS) approach.
Selection criteria were: pure tone audiogram <50dB loss and speech discrimination
score >50% (50/50 criterion; AAO-HNS class A-B). In relation to maximum diameter,
we identified 2 size-groups: A) <=2cm (13 cases); B) >2cm (12 cases). HP attempt
was assisted by intraoperative ABR evoked by LS CE-Chirp(r) acoustic stimuli.
RESULTS: Mean age was 44,3 years (20-64); average maximum diameter 2,04cm (8
40mm). Total and nearly-total (>95%) resection was possible in all. Mortality and
major morbidity were zero. In all, FN was anatomically and functionally
preserved; in 10 an incomplete FN deficit (House-Brackmann II and III) was
followed by complete recovery (House-Brackmann I). SUH preservation rate was 52%,
with significant differences in relation to size: 61,5% group A and 41,7% group B
(p = 0,014). Postoperative AAO-HNS C (serviceable) hearing was observed in 36%,
deafness in 12%. CONCLUSION: Microsurgery represents a valid therapeutic option
for small growing VS with SUH. Our data confirm that RS removal of VS with
intraoperative ABR monitoring allows good rate of SUH preservation, especially if
maximum diameter does not exceed 2cm. LS-CE-Chirp ABR represent a safe and
effective method for monitoring cochlear nerve, with fast and clear
intraoperative neurophysiological feedback.
PMID- 29334640
TI - Not single brain areas but a network is involved in language: Applications in
presurgical planning.
AB - OBJECTIVES: Language is an important human function, and is a determinant of the
quality of life. In conditions such as brain lesions, disruption of the language
function may occur, and lesion resection is a solution for that. Presurgical
planning to determine the language-related brain areas would enhance the chances
of language preservation after the operation; however, availability of a
normative language template is essential. PATIENTS AND METHODS: In this study,
using data from 60 young individuals who were meticulously checked for mental and
physical health, and using fMRI and robust imaging and data analysis methods,
functional brain maps for the language production, perception and semantic were
produced. RESULTS: The obtained templates showed that the language function
should be considered as the product of the collaboration of a network of brain
regions, instead of considering only few brain areas to be involved in that.
CONCLUSION: This study has important clinical applications, and extends our
knowledge on the neuroanatomy of the language function.
PMID- 29334641
TI - Do clinically anxious children cluster according to their expression of factors
that maintain child anxiety?
AB - BACKGROUND: Cognitive Behaviour Therapy (CBT) is an effective treatment for
childhood anxiety disorders, yet a significant proportion of children do not
benefit from it. CBT for child anxiety disorders typically includes a range of
strategies that may not all be applicable for all affected children. This study
explored whether there are distinct subgroups of children with anxiety disorders
who are characterized by their responses to measures of the key mechanisms that
are targeted in CBT (i.e. interpretation bias, perceived control, avoidance,
physiological arousal, and social communication). METHODS: 379 clinically anxious
children (7-12 years) provided indices of threat interpretation, perceived
control, expected negative emotions and avoidance and measures of heart rate
recovery following a speech task. Parents also reported on their children's
social communication difficulties using the Social Communication Questionnaire
(SCQ). RESULTS: Latent profile analysis identified three groups, reflecting (i)
'Typically anxious' (the majority of the sample and more likely to have
Generalized anxiety disorder); (ii) 'social difficulties' (characterized by high
SCQ and more likely to have social anxiety disorder and be male); (iii)
'Avoidant' (characterized by low threat interpretation but high avoidance and low
perceived control). LIMITATIONS: Some measures may have been influenced by
confounding variables (e.g. physical variability in heart rate recovery). Sample
characteristics of the group may limit the generalizability of the results.
CONCLUSIONS: Clinically anxious children appear to fall in to subgroups that
might benefit from more targeted treatments that focus on specific maintenance
factors. Treatment studies are now required to establish whether this approach
would lead to more effective and efficient treatments.
PMID- 29334642
TI - Examining the latent structure mechanisms for comorbid posttraumatic stress
disorder and major depressive disorder.
AB - BACKGROUND: Posttraumatic stress disorder (PTSD) is a complex psychiatric illness
that can be difficult to diagnose, due in part to its comorbidity with major
depressive disorder (MDD). Given that researchers have found no difference in
prevalence rates of PTSD and MDD after accounting for overlapping symptoms, the
latent structures of PTSD and MDD may account for the high comorbidity. In
particular, the PTSD Negative Alterations in Cognition and Mood (NACM) and
Hyperarousal factors have been characterized as non-specific to PTSD. Therefore,
we compared the factor structures of the Diagnostic and Statistical Manual of
Mental Disorders, 5thedition (DSM-5) PTSD and MDD and examined the mediating role
of the PTSD NACM and Hyperarousal factors on the relationship between MDD and
PTSD symptom severity. METHODS: Participants included 598 trauma-exposed veterans
(Mage = 48.39, 89% male) who completed symptom self-report measures of DSM-5 PTSD
and MDD. RESULTS: Confirmatory factor analyses indicated an adequate-fitting four
factor DSM-5 PTSD model and two-factor MDD model. Compared to other PTSD factors,
the PTSD NACM factor had the strongest relationship with the MDD Affective
factor, and the PTSD NACM and Hyperarousal factors had the strongest association
with the MDD Somatic factor. Further, the PTSD NACM factor explained the
relationship between MDD factors and PTSD symptom severity. More Affective and
Somatic depression was related to more NACM symptoms, which in turn were related
to increased severity of PTSD. LIMITATIONS: Limitations include the reliance on
self-report measures and the use of a treatment-seeking, trauma-exposed veteran
sample which may not generalize to other populations. CONCLUSIONS: Implications
concerning the shared somatic complaints and psychological distress in the
comorbidity of PTSD and MDD are discussed.
PMID- 29334643
TI - Longitudinal determinants of depression among World Trade Center Health Registry
enrollees, 14-15 years after the 9/11 attacks.
AB - BACKGROUND: Exposure to the September 11, 2001 (9/11) terrorist attacks has been
found to be associated with posttraumatic stress disorder (PTSD) and comorbid
PTSD and depression up to 10-11 years post-disaster. However, little is known
about the longitudinal predictors of mental health conditions over time. METHODS:
We examined longitudinal determinants of depression within strata of PTSD among
21,258 enrollees of the World Trade Center Health Registry who completed four
questionnaires over 14 years of follow-up (Wave 1 in 2003-04; Wave 2 in 2005-06;
Wave 3 in 2011-12; and Wave 4 in 2015-16). PTSD status was measured using the
PTSD checklist on all four waves and defined as a score of >= 44; depression was
assessed using the 8-item Patient Health Questionnaire at Waves 3 and 4 and
defined as a score of >= 10. RESULTS: Across Waves 3 and 4, 18.6% experienced
depression, and it was more common among those who ever had PTSD (56.1%) compared
with those who had not (5.6%). Across PTSD strata, predictors of depression
included low income, unemployment, low social integration and support, post-9/11
traumatic life events, and chronic physical illness. These factors also decreased
the likelihood of recovering from depression. LIMITATIONS: Depression symptoms
were not measured at Waves 1 and 2; data was self-reported. CONCLUSIONS: These
findings highlight the substantial burden of depression in a trauma-exposed
population 14-15 years post-disaster, especially among those with PTSD. Similar
life stressors predicted the course of depression among those with and without
PTSD which may inform public health and clinical interventions.
PMID- 29334644
TI - Predictors of remission from probable depression among Hong Kong adolescents - A
large-scale longitudinal study.
AB - BACKGROUND: This study investigated the incidence of remission from probable
depression among adolescents in Hong Kong. Remissions were defined as having
Center for Epidemiological Studies Depression Scale (CESD) scores changed from
>=16 at baseline to <16 over the 12-month follow-up period. The study tested the
predictors of remissions, including perceived changes in family support, self
efficacy, self-esteem, positive affect, negative events, social anxiety, and
loneliness. METHODS: The study surveyed 9666 secondary school students and
identified 5487 (57%) students with probable depression in Hong Kong. A
questionnaire assessing the levels of the aforementioned variables was completed
at baseline and at the 12-month follow-up. RESULTS: Among participants with
probable depression at baseline, 23.2% remitted from depression at follow-up.
Remissions were more common among males than females. Univariate logistic
regression showed that perceived changes in all the aforementioned variables
significantly predicted remission for both males and females. The same is true
for most of these variables when they were entered together into multiple
logistic regression models (with and without controlling for baseline CESD
scores), except for family support in the female model and self-efficacy in both
male and female models. LIMITATIONS: Limitations include potential self-report
bias and only one follow-up observation over time. The design treats cases of
probable mild to severe depression as a single group (CESD>=16). CONCLUSIONS: The
findings are potentially useful for designing and guiding related intervention
programs. Results highlight the importance of long-term follow-up of those
screened as probable depression to understand the course of changes in levels of
depression.
PMID- 29334645
TI - Co-morbid depressive disorder is associated with better neurocognitive
performance in first episode schizophrenia spectrum.
AB - BACKGROUND: Both major depressive disorder (MDD) and first episode schizophrenia
spectrum (FES) are associated with significant neurocognitive deficits. However,
it remains unclear whether the neurocognitive deficits in individuals with FES
are more severe if there is comorbid depressive disorder. The aim of this study
was to compare the neurocognitive profiles between those with and without full
threshold depressive disorder in FES. METHOD: This study involved secondary
analysis of baseline data from a randomized controlled trial of vocational
intervention for young people with first-episode psychosis (N = 82; age range: 15
25 years). RESULTS: Those with full-threshold depressive disorder (n = 24) had
significantly better information processing speed than those without full
threshold depressive disorder. Severity of depressive symptoms was also
associated with better information processing speed. LIMITATIONS: In additional
to the cross-sectional design, limitations of this study include the absence of
assessing insight as a potential mediator. CONCLUSIONS: After the first psychotic
episode, it could be speculated that those with better information processing
speed may be more likely to develop full-threshold depressive disorder, as their
ability to efficiently process information may allow them to be more aware of
their situations and environments, and consequently to have greater insight into
the devastating consequences of FES. Such novel findings support the examination
of full-threshold depressive disorder in relation to neurocognitive performance
across illness phases in future work.
PMID- 29334646
TI - 17beta-estradiol improves the efficacy of exploited autologous bone marrow
derived mesenchymal stem cells in non-union radial defect healing: A rabbit
model.
AB - Exploiting mesenchymal stem cells (MSCs) appears to be an appealing alternative
to the traditional clinical approach in the treatment of non-union bone defects.
It has been shown that 17beta-estradiol improves the osteogenesis and
proliferation potential of the MSCs via estrogen receptors. We investigated the
effect of 17beta-estradiol on exploiting autologous BMSCs (bone marrow-derived
MSCs) for the purpose of healing of radial non-union segmental defect in rabbit.
Twenty rabbits were divided into 4 experimental groups: 1. Control group; 2. MSC
treatment group; 3. 17beta-estradiol (E2) treatment group; and 4. E2+MSC
treatment group. Isolated BMSCs were seeded in a critical-sized defect on radial
mid-diaphysis that was filled with autologous fibrin clot differently in 4
groups: 1. intact fibrin clot (control); 2. Fibrin clot containing MSCs; 3.
Estradiol; and 4. E2 and MSCs. Defect healing was assessed by radiological (week
0, 2, 4, 6, 8 and 10) and histopathological evaluation (week 10). Radiological
evaluation data demonstrated that quantities for the E2+MSC group were
significantly the greatest in comparison with the other groups at week 4 to 10
inclusive. Moreover, Histopathological evaluation indicated that the E2+MSC group
had the highest score which was significantly greater than the E2 group and the
control group (P<0.05). In-vivo application of in situ 17beta-estradiol provides
the seeded BMSCs with improved osteogenic capacity in tandem with an accelerated
rate of bone healing. This obviously more qualified approach that yields in a
shorter time appears to be promising for the future cell-based clinical
treatments of the non-union bone fractures. Exploiting mesenchymal stem cells
(MSCs) appears to be an appealing alternative to the traditional clinical
approach in the treatment of non-union bone defects. It has been shown that
17beta-estradiol improves the osteogenesis and proliferation potential of the
MSCs via estrogen receptors. We investigated the effect of 17beta-estradiol on
exploiting autologous BMSCs (bone marrow-derived MSCs) for the purpose of healing
of radial non-union segmental defect in rabbit. Twenty rabbits were divided into
4 experimental groups: 1. Control group; 2. MSC treatment group; 3. 17beta
estradiol (E2) treatment group; and 4. E2+MSC treatment group. Isolated BMSCs
were seeded in a critical-sized defect on the radial mid-diaphysis that was
filled with autologous fibrin clot differently in 4 groups: 1. intact fibrin clot
(control); 2. Fibrin clot containing MSCs; 3. Estradiol; and 4. E2 and MSCs.
Defect healing was assessed by radiological (week 0, 2, 4, 6, 8 and 10) and
histopathological evaluation (week 10). Radiological evaluation data demonstrated
that quantities for the E2+MSC group were significantly the greatest in
comparison with the other groups at week 4 to 10 inclusive. Moreover,
Histopathological evaluation indicated that the E2+MSC group had the highest
score which was significantly greater than the E2 group and the control group
(P<0.05). In-vivo application of in situ 17beta-estradiol provides the seeded
BMSCs with improved osteogenic capacity in tandem with an accelerated rate of
bone healing. This obviously more efficient approach that yields in a shorter
time appears to be promising for future cell-based clinical treatments of the non
union bone fractures.
PMID- 29334647
TI - Time-resolved decoding of planned delayed and immediate prehension movements.
AB - Different contexts require us either to react immediately, or to delay (or
suppress) a planned movement. Previous studies that aimed at decoding movement
plans typically dissociated movement preparation and execution by means of
delayed-movement paradigms. Here we asked whether these results can be
generalized to the planning and execution of immediate movements. To directly
compare delayed, non-delayed, and suppressed reaching and grasping movements, we
used a slow event-related functional magnetic resonance imaging (fMRI) design. To
examine how neural representations evolved throughout movement planning,
execution, and suppression, we performed time-resolved multivariate pattern
analysis (MVPA). During the planning phase, we were able to decode upcoming
reaching and grasping movements in contralateral parietal and premotor areas.
During the execution phase, we were able to decode movements in a widespread
bilateral network of motor, premotor, and somatosensory areas. Moreover, we
obtained significant decoding across delayed and non-delayed movement plans in
contralateral primary motor cortex. Our results demonstrate the feasibility of
time-resolved MVPA and provide new insights into the dynamics of the prehension
network, suggesting early neural representations of movement plans in the primary
motor cortex that are shared between delayed and non-delayed contexts.
PMID- 29334648
TI - Using mass struvite precipitation to remove recalcitrant nutrients and
micropollutants from anaerobic digestion dewatering centrate.
AB - The primary objective of this research was to remove recalcitrant nutrients from
anaerobically digested sludge dewatering centrate. A struvite precipitation
methodology is proposed where salt crystals are encouraged to ballast colloidal
particles through heterogeneous nucleation and subsequent crystal growth. The
secondary objective was to assess presence of micropollutants in precipitates.
Four biologically unique dewatering centrates were used to test the precipitation
methodology on the variety of anaerobic digester configurations that can be
expected from municipal wastewater treatment plant. The effect of digestion
sludge retention time (2 day, 20 day) and digestion temperature (35 degrees C,
55 degrees C) on the removal of dissolved unreactive phosphorus (P) and nitrogen
(N) was monitored. Averaged across all four centrates, the precipitation
methodology resulted in dissolved unreactive P and N removal of 82.4% and 66.6%,
respectively. Antimicrobial contaminants (triclosan, triclocarban) were observed
in the precipitates at minute concentrations (<18 ng/g-dry solids). Therefore,
mass struvite precipitation can provide a means of recalcitrant nutrient
treatment and reactive nutrient recovery without the micropollutant burden of
biosolids land application.
PMID- 29334649
TI - Determining variables that influence the phosphorus content of waste
stabilization pond algae.
AB - Waste stabilization ponds (WSP) are one of the most common forms of wastewater
treatment for smaller communities globally, but have poor phosphorus removal. It
is known that WSP algae can accumulate polyphosphate within their cells in excess
of that needed for cell function. If polyphosphate accumulation could be
triggered at the higher range of WSP cell concentrations, phosphorus removal from
domestic wastewater could be significantly improved. However, this phenomenon is
sporadic and still not fully understood. With a view of building a fundamental
understanding to underpin the engineering of a new phosphorus removal process,
this paper examines eight previously untested variables that may influence the
cellular phosphorus content of WSP biomass. Although calcium, magnesium, and
potassium are key constituents of polyphosphate granules, the concentrations
tested were not limiting to polyphosphate accumulation. While literature also
pointed to inoculum characteristics as potentially having an impact, no
significance was found in this research. Conversely, three important new triggers
where identified that significantly (90% confidence) affected the cellular
phosphorus content of WSP biomass. An increase in cellular phosphorus content was
triggered by decreasing the organic load, or allowing the pH to increase as
compared to pH control. By contrast, the presence of mixing decreased the
phosphorus content of the WSP biomass.
PMID- 29334650
TI - Environmentally relevant concentrations of glibenclamide induce oxidative stress
in common carp (Cyprinus carpio).
AB - The hypoglycemic pharmaceutical glibenclamide (GLB) is widely used around the
world. This medication is released into the environment by municipal, hospital
and industrial wastewater discharges. Although there are reports of its
environmental occurrence in the scientific literature, toxicity studies on
aquatic species of commercial interest such as the common carp Cyprinus carpio
are scarce. The present study aimed to evaluate the oxidative stress induced on
C. carpio by environmentally relevant concentrations of GLB. Biomarkers of
oxidative damage such as hydroperoxide content, lipid peroxidation and protein
carbonyl content were evaluated as well as the activity of the antioxidant
enzymes superoxide dismutase and catalase. The concentration of GLB was
determined in water as well as in gill, liver, muscle, brain and blood of carp at
12, 24, 48, 72 and 96 h. The findings obtained in the study prove that GLB
induces increases in biomarkers of oxidative damage and antioxidant enzyme
activity in the teleost C. carpio, that this response is not concentration
dependent and that the organs evaluated bioconcentrate this hypoglycemic agent.
These findings permit us to conclude that the presence of GLB in water bodies
represents a risk for aquatic species.
PMID- 29334652
TI - Insight into the expression variation of metal-responsive genes in the seedling
of date palm (Phoenix dactylifera).
AB - Phytochelatin synthase and metallothionein gene expressions were monitored via
qPCR in order to investigate the molecular mechanisms involved in Cd and Cr
detoxification in date palm (Phoenix dactylifera). A specific reference gene
validation procedure using BestKeeper, NormFinder and geNorm programs allowed
selection of the three most stable reference genes in a context of Cd or Cr
contamination among six reference gene candidates, namely elongation factor
alpha1, actin, aldehyde dehydrogenase, SAND family, tubulin 6 and TaTa box
binding protein. Phytochelatin synthase (pcs) and metallothionein (mt) encoding
gene expression were induced from the first days of exposure. At low Cd stress
(0.02 mM), genes were still up-regulated until 60th day of exposure. At the
highest metal concentrations, however, pcs and mt gene expressions decreased. pcs
encoding gene was significantly up-regulated under Cr exposure, and was more
responsive to increasing Cr concentration than mt encoding gene. Moreover,
exposure to Cd or Cr influenced clearly seed germination and hypocotyls
elongation. Thus, the results have proved that both analyzed genes participate in
metal detoxification and their expression is regulated at transcriptional level
in date palm subjected to Cr and Cd stress. Consequently, variations of
expression of mt and pcs genes may serve as early-warning biomarkers of metal
stress in this species.
PMID- 29334651
TI - Effects of perinatal fluoride exposure on the expressions of miR-124 and miR-132
in hippocampus of mouse pups.
AB - To investigate the effects of perinatal fluoride exposure on learning and memory
ability of mouse offspring, ICR female mice were received different doses of
sodium fluoride (0, 25, 50, 100 mg/L NaF) from pregnant day 7 to lactational day
21. Pups were exposed to fluoride through the cord blood and breast milk. Open
field test showed that compared to the control group, perinatal fluoride exposure
significantly decreased the number of entries into the center zone in 100 mg/L
NaF group. In the eight-arm maze test, the number of working memory errors,
reference memory errors, and the total arm entries were significantly increased
in fluoride treatment groups, compared to the control group. Additionally, 100
mg/L NaF significantly elevated the expression levels of miR-124, miR-132, and
DiGeorge syndrome chromosomal region 8 (DGCR8) in hippocampus of mouse pups at
postnatal day (PND) 21. Contrarily, methyl CpG binding protein 2 (MeCP2) were
dramatically reduced in 50 and 100 mg/L NaF groups, while cAMP-response element
binding protein (CREB) mRNA level was significantly decreased in all fluoride
groups. These findings suggested that the impairment of learning and memory in
mouse offspring induced by perinatal fluoride exposure may partly result from the
enhanced miR-124 and miR-132 and the alterations of their target genes.
PMID- 29334653
TI - Depletion study, withdrawal period calculation and bioaccumulation of
sulfamethazine in tilapia (Oreochromis niloticus) treated with medicated feed.
AB - The residue depletion of sulfamethazine (SMZ) was evaluated in tilapia
(Oreochromis niloticus) after 11 days of administration of medicated feed
containing SMZ, at the dose of 422 mg/kg body weight (bw). The determination of
SMZ in feed and tilapia fillet was carried out using the QuEChERS approach for
sample preparation, and high performance liquid chromatography with diode array
detector (HPLC-DAD) and ultra-high performance liquid chromatography-quadrupole
time-of-flight mass spectrometry (UPLC-QToF-MS) for quantitation, respectively.
Both methods were validated based on international and Brazilian guidelines and
shown to be suitable for the intended purposes. The withdrawal period to reach
the maximum residue level (MRL) of 100 MUg/kg, according to the European Union
(EU) legislative framework to all substances belonging to the sulfonamide (SA)
group (EU, 2010), was 10 days (260 degrees C-day). After treatment, the maximum
level of SMZ accumulation in the tilapia muscle was 1.6 mg/kg. SMZ was shown to
be quickly excreted by tilapia. Thus, considering the acceptable daily intake of
SMZ established by the Codex Commission (0-0.05 mg/kg bw), and a factor of 5
times the upper amount of fish consumption in Brazil (38 kg/year), this study
showed that there is a low risk of adverse effects to consumers. This study
offers subsidies not only for the establishment of public policies with regard to
the use of veterinary drugs currently not allowed in a country by their legal
legislative framework for fish farming, but also to fish producers for the proper
handling to ensure safe fish fillets.
PMID- 29334655
TI - How yeast coordinates metabolism, growth and division.
AB - All cells, especially single cell organisms, need to adapt their metabolism,
growth and division coordinately to the available nutrients. This coordination is
mediated by extensive cross-talk between nutrient signaling, metabolism, growth,
and the cell division cycle, which is only gradually being uncovered: Nutrient
signaling not only controls entry into the cell cycle at the G1/S transition, but
all phases of the cell cycle. Metabolites are even sensed directly by cell cycle
regulators to prevent cell cycle progression in absence of sufficient metabolic
fluxes. In turn, cell cycle regulators such as the cyclin-dependent kinase
directly control metabolic fluxes during cell cycle progression. In this review,
I highlight some recent advances in our understanding of how metabolism and the
cell division cycle are coordinated in the model organism Saccharomyces
cerevisiae.
PMID- 29334654
TI - PHBV polymer supported denitrification system efficiently treated high nitrate
concentration wastewater: Denitrification performance, microbial community
structure evolution and key denitrifying bacteria.
AB - Biodegradable polymer supported denitrification (BPD) system shows good
denitrification performance for the wastewater with low nitrate concentrations.
In this study, a BPD system using Poly (3-hydroxybutyrate-co-3-hydroxyvalerate)
(PHBV) polymer as carbon source was developed to treat the wastewater with high
nitrate concentrations. The denitrification performance, utilization ratio of
PHBV polymers, and microbial community structure evolution and key denitrifying
bacteria were comprehensively studied. Results indicated that an average nitrate
removal efficiency of 99% could be achieved with an influent NO3--N concentration
of 100 mg L-1 and a hydraulic retention time (HRT) of 7.25 h. Mass balance model
predicted that 80% of the PHBV polymers were consumed by denitrifying bacteria,
close to 72% consumption in real condition, suggesting the model might be useful
for PHBV polymers management in BPD system. Further, the bacterial community
structures varied along the bioreactor profile, which closely linked to the
concentration profiles of nitrate and ammonia. Metatranscriptomic analysis
identified the key denitrifying bacteria as Comamonas, Acidovorax and
Dechloromonas. The PHBV supported denitrification system developed in this study
shows potential for removal of high concentration of nitrate from wastewater.
PMID- 29334656
TI - Activated protein C suppresses osteoclast differentiation via endothelial protein
C receptor, protease-activated receptor-1, sphingosine 1-phosphate receptor, and
apolipoprotein E receptor 2.
AB - INTRODUCTION: Bone remodeling relies on a delicate balance between formation and
resorption of bone tissues, processes in which bone-forming osteoblasts and bone
resorbing osteoclasts play central roles. Recently, we reported that
anticoagulant activated protein C (APC) promotes osteoblast proliferation, but
the role of the blood coagulation system in bone remodeling remains unclear. In
this study, to further elucidate the relationship between bone remodeling and
blood coagulation, we investigated the effect of APC on osteoclast
differentiation. MATERIALS AND METHODS: Normal human osteoclast precursor cells
were cultured in their growth medium including soluble RANKL, M-CSF, and FBS, and
on days 4 and 7, the culture medium was replaced with the same medium containing
various concentrations of APC, protein C (PC), sphingosine 1-phosphate (S1P)
receptor agonist, FTY720, or APC+various substances without FBS. On day 8, TRAP
positive multinucleated cells (>=3 nuclei) were counted manually using a light
microscope. The effects of APC on NF-kappaB and NFATc1 activation were evaluated
using specific ELISA. RESULTS: APC suppressed RANKL-induced osteoclast
differentiation, and this APC-induced suppression of osteoclast differentiation
was inhibited by zymogen protein C and aprotinin, a serine protease inhibitor.
Immunohistochemistry and RT-PCR analyses suggested that endothelial protein C
receptor (EPCR) and protease-activated receptor-1 (PAR-1) were expressed in
osteoclast precursor cells and osteoclasts. Both anti-PAR-1 antibody and anti
EPCR antibody (RCR-252), which blocks APC binding to EPCR, inhibited the APC
induced suppression of osteoclast differentiation. FTY720 had no effect on
osteoclast differentiation. However, FTY 720 and S1P receptor antagonist, VP
23019, inhibited the APC-induced suppression of osteoclast differentiation. On
the other hand, recombinant soluble human ApoER2 and anti-human ApoER2 inhibited
the APC-induced suppression of osteoclast differentiation. Further, APC had no
effect on NF-kappaB and NFATc1 activation. CONCLUSIONS: APC suppresses human
osteoclast differentiation mainly by inhibiting the formation of multinucleated
cells via EPCR, PAR-1, S1P receptor, and ApoER2 in a manner that depends on APC
protease activity.
PMID- 29334657
TI - Relationship of obsessive-compulsive symptoms to clinical variables and cognitive
functions in individuals at ultra high risk for psychosis.
AB - Few studies have investigated the relationship between obsessive-compulsive
symptoms (OCS) and clinical variables, and cognition in individuals at ultra high
risk (UHR) for psychosis. The aim of this study was to evaluate the frequency of
OCS and their relationship with clinical variables and cognitive functions in
individuals at UHR. Eighty-four individuals at UHR for psychosis were
administered the Brief Psychiatric Rating Scale, the Yale-Brown Obsession
Compulsion Symptom Check List and, the Calgary Depression Scale for
Schizophrenia. A cognitive test battery was also applied. We compared the
clinical, functional, and cognitive parameters of individuals at UHR with and
without OCS and healthy controls. Thirty-five percent of the UHR sample had at
least two obsessions/compulsions. The duration of subthreshold psychotic symptoms
was longer in individuals with OCS. Those who can work/study before first
presentation were more frequent in OCS-positive group. CDSS scores were higher in
those with OCS. Compared to controls, OCS-negative group's performance was worse
in 8 cognitive test items, while OCS-positive group performed worse in only one
cognitive test item. Our findings suggest that OCS are common in the UHR group.
OCS might be related to higher level of depression, but better work/study
performance, and less cognitive deficits in UHR group.
PMID- 29334658
TI - Contextual determinants of psychopathology. The singularity of attachment as a
predictor of mental dysfunction.
AB - The general aim of this research is to evaluate the singular weight of attachment
relationships in psychopathology, to determine the point to which these
relationships cannot be subsumed by other variables that are famously related to
attachment, such as experience of stressful life events, social support, and
coping styles. 172 people treated in mental health centers provided data related
to these four aspects and about manifestations of psychopathology. Multiple
linear regression analyses determined that 51% of the variance in the level of
symptomatology is explained with six variables: two related to adult attachment
(fear of rejection and abandonment in romantic relationships, and the degree of
similarity to the fearful prototype), one related to social support (family
appreciation), one to life events (overall perceived stress), and two to coping
style (cognitive restructuring and social withdrawal). Fear of rejection was the
variable accounting for the most variance. The findings suggest that adult
attachment is a non-redundant individual factor associated with manifestations of
psychological dysfunction and highlight the desirability of taking attachment
history into account in clinical practice.
PMID- 29334659
TI - Serum zinc levels in acute psychiatric patients: A case series.
AB - Zinc dysregulation is linked to neuropsychiatric disorders and a beneficial
response to zinc supplementation has been demonstrated for depression. In this
case series, we examined serum zinc levels with respect to clinical factors among
20 acutely ill psychiatric cases admitted to a large urban public hospital. The
results showed frank clinical zinc insufficiency in a quarter of the subjects.
Group-wise analyses showed a significant association between reduced serum zinc
and diagnosis of depression, and reduced serum zinc in those with aggressive,
assaultive, or violent behaviors. By contrast, relatively elevated zinc levels
were observed in a subset of psychotic cases on antipsychotics and mood
stabilizers who had no mood symptoms. In summary, clinical zinc insufficiency was
common in these acutely admitted psychiatric cases. Zinc supplementation may
ameliorate symptoms in certain cases and should be considered in treatment
planning. A separate patient group had elevated zinc levels, which could
conceivably be pathogenic. Larger studies are needed to confirm and extend this
pilot data.
PMID- 29334660
TI - Global proteomic analysis of water buffalo (Bubalus bubalis) saliva at different
stages of estrous cycle using high throughput mass spectrometry.
AB - Accurate and efficient detection of estrus is one of the major constraints for
exploitation of the production potential of buffalo owing to its poor
manifestation of estrus signs, seasonal differences in expression and higher
incidences of silent estrus (29%). The current study focused on identification of
estrus specific candidate proteins in saliva of buffaloes. Estrus was detected
based on behavioral signs in response to the teaser and changes in reproductive
organs and confirmed by per-rectal examination, trans-rectal USG of reproductive
organs, cervico-vaginal mucus characteristics and blood serum progesterone
estimation. Day of onset of estrus was considered as day 0 and day -3, +3, +10
were considered as proestrus, metestrus and diestrus stage of the estrous cycle
respectively. A total of 19 animals and their 38 estrous cycles (two from each)
were included in this study. Saliva was collected from these animals during
different stages of estrous cycle. Out of these, 08 animals were selected for
global proteome analysis of saliva using in-solution digestion and nano-LC-MS/MS.
A total of 275, 371, 304 and 565 proteins were identified with >=2 peptides
during proestrus, estrus, metestrus and diestrus stages of estrous cycle. Among
the identified proteins 31, 62, 32 and 104 proteins were found specific to
proestrus, estrus, metestrus and diestrus stage of the estrous cycle. Few
salivary proteins such as Cullin-associated NEDD8-dissociated protein 1, Heat
shock 70 kDa protein 1A, 17-beta-hydroxysteroid dehydrogenase type 1, Inhibin
beta A chain, testin were identified as estrus specific and are important for
estrus physiology. Taken together, these estrus specific proteins could be
considered as the candidate biomarker for detection and confirmation of estrus in
buffalo after thorough validation.
PMID- 29334661
TI - Altered expression of IL-1beta, IL-1RI, IL-1RII, IL-1RA and IL-4 could contribute
to anovulation and follicular persistence in cattle.
AB - Cystic ovarian disease (COD) is an important cause of infertility in dairy
cattle. The main signs of this infertility are ovulation failure and follicular
persistence. The aim of this study was to examine the expression of the cytokines
IL-1beta, IL-1RI, IL-1RII, IL-1RA and IL-4 in ovarian follicular structures at
different times of persistence in a model of follicular persistence induced by
prolonged administration of progesterone in dairy cows. Protein expression of IL
1beta, IL-1RI, IL-1RII, IL-1RA and IL-4 was evaluated by immunohistochemistry.
Additionally, IL-1beta and IL-4 concentrations in follicular fluid and serum were
determined by ELISA. In granulosa cells, IL1-RII and IL-4 expression was higher
in follicles with different persistence times than in the control dominant
follicles. IL-1RA expression was higher in persistent follicles of the P15 group
(15 days of follicular persistence) than in those of the control group. In theca
cells, IL-1RII expression was higher in persistent follicles of the P0 group
(expected time of ovulation) than in dominant follicles from the control group (p
< .05) and the other persistence groups, whereas IL-4 expression was higher in
persistent follicles of groups P0 and P15 than in the dominant follicles of the
control group (p < .05). Differences between serum and follicular fluid within
each group were detected only in P0 for IL-1beta, and in the control, P10 and P15
groups for IL-4 (p < .05). These results complement previous results, evidencing
that early development of COD in cows is concurrent with an altered expression of
cytokines in different ovarian follicular structures and may contribute to the
follicular persistence and ovulation failure found in cattle with follicular
cysts.
PMID- 29334662
TI - Aqueous extracts of two tropical ethnobotanicals (Tetrapleura tetraptera and
Quassia undulata) improved spatial and non-spatial working memories in
scopolamine-induced amnesic rats: Influence of neuronal cholinergic and
antioxidant systems.
AB - BACKGROUND: Tetrapleura tetraptera (TT) and Quassia undulata (QU) are two
predominant tropical ethnobotanicals with various medicinal values but are
commonly used in folklore for the treatment of mental illness without justifiable
mechanisms of action. AIM OF THE STUDY: To investigate the effects of aqueous
extracts from TT fruits and QU leaves on the spatial and non-spatial working
memory, antioxidant status and activities of neuronal marker enzymes of
scopolamine-induced amnesic rats and thus, understand the possible mechanism of
action of these plants. MATERIALS AND METHODS: Fifty-five albino rats were
divided into eleven groups. Group I (normal rats) received normal saline (p.o),
Group II-V (normal rats) administered with 50 and 300 mg/kg of each extract group
VI (induced rats) received 2 mg/kg of scopolamine (i.p.), groups VII-X (induced
rats) pretreated with 50 and 300 mg/kg of TT and QU extracts (p.o) before
scopolamine administration, group XI (induced rats) treated with 2.5 mg/kg of
donepezil. The treatment lasted for 14 days and amnesia was induced by a single
dose of 2 mg/kg of scopolamine on the last day. Spatial (Y-maze) and non-spatial
(novel objectect recoginiton test) working memories of the rats were tested.
Thereafter, the animals were sacrificed and homogenates of isolated brain samples
were assayed for cholinesterase activity and malondialdehyde (MDA) content. The
phenolic characterisation of the samples was also carried out using HPLC-DAD
chromatography. RESULTS: Administration of 2 mg/kg of scopolamine brought about a
decrease in spatial and non-spatial memory indeces, increase in
acetylcholinesterase and butyrylcholinesterase activities, as well as increased
MDA content compared to the control. However, pretreatment with both extracts
improved both spatial and non-spatial working memories and ameliorated the
increased enzyme activities and MDA contents. Furthermore, the HPLC-DAD
characterization of the extracts revealed the presence of p-coumaric acid, rutin,
catechin, ellagic acid, quercetin, caffeic acid, chlorogenic acid and galic acid.
CONCLUSION: The ability of the extracts to improved cognitive function and
ameliorate impairment in cholinergic enzyme activities and antioxidant status in
scopolamine-induced amnesic rats could help justify the possible neuroprotective
properties of TT and QU and also explain possible mechanism of action of these
ethnobotanicals as obtained in folklore medical practices.
PMID- 29334663
TI - Acute toxicity screening of different extractions, components and constituents of
Polygonum multiflorum Thunb. on zebrafish (Danio rerio) embryos in vivo.
AB - Polygonum multiflorum Thunb. has been used widely in East Asia in treatment of
diseases associated with aging. However, there are many reports referred to the
toxicity of P. multiflorum, especially for liver adverse reactions. The toxicity
of it is caused by over dosage or by the herb itself remains unclear. The aim of
this study was to study the toxicity of different extractions, components and
constituents of P. multiflorum, which were assessed in zebrafish embryos.
Firstly, the difference of extracting solvent to the toxicity of P. multiflorum
was researched to probe the influence of usages to the safety of P. multiflorum.
The toxicity of 70% EtOH extract is considerably higher than that of other
extracts. Secondly, 70% EtOH extract was subjected to macroporous resin (DM-8)
eluting with a gradient of water and EtOH (H2O, 25% EtOH, 40% EtOH and 95% EtOH)
to give four components (A-D). The toxicity of the component (D) showed higher
than the other components (A-C). Thus, the component (D) was taken more
attentions to research. Lastly, study on the chemical constituents of the
component (D), 27 compounds, including 7 anthraquinones (1-7), 8 stilbenes (8
15), 7 anthrones (16-22), 3 cinnamic acid amides (23-25), 2 naphthols (26-27)
were isolated and assessed in zebrafish embryos. Compounds 1-3, 16-22 and 26-27
showed severe toxicity against the zebrafish embryos while other compounds, such
as stilbenes, showed no obvious toxicity.
PMID- 29334664
TI - Methyl dehydroabietate counters high fat diet-induced insulin resistance and
hepatic steatosis by modulating peroxisome proliferator-activated receptor
signaling in mice.
AB - The aim of this study was to investigate the therapeutic effects of methyl
dehydroabietate (mDA) on adipocyte differentiation in 3T3-L1 preadipocytes and
obesity characteristics induced by high-fat diet (HFD) in mice. Adipocyte
differentiation in 3T3-L1 cells was evaluated after 14 days of incubation with
mDA. mDA enhanced adipocyte differentiation in 3T3-L1 cells. For the in vivo
evaluation, five-week-old male C57BL/6J mice were fed HFD or normal CE-2 diet
(control) for eight weeks. During the experimental period, mice were administered
mDA (50 mg/kg, p.o.) as an olive oil emulsion (containing 10% ethanol), and body
weights were measured weekly. At the end of the experiment, the mice were
euthanized after 16 h fasting period, and plasma samples were collected. The
liver, kidney, and epididymal adipose tissues were collected and weighed. It
significantly decreased body weight, adipose tissue weight, and plasma levels of
glucose, insulin, leptin, and pro-inflammatory cytokines compared with that in
the HFD group, and markedly reduced the impairment in glucose tolerance in obese
mice. Furthermore, mDA reduced HFD-induced adipocyte hypertrophy and the
formation of hepatic lipid droplets. Moreover, it induced the expression of
proliferator-activated receptor alpha (PPARalpha) in the liver and PPARgamma in
the adipose tissues. Our findings demonstrate that mDA reduces obesity-induced
glucose and insulin tolerance by inducing PPAR expression.
PMID- 29334665
TI - I-7ab inhibited the growth of TNBC cells via targeting HDAC3 and promoting the
acetylation of p53.
AB - Triple negative breast cancer (TNBC) is a heterogenous disease with high
aggressive and poor outcome. The lack of biomarkers and targeted therapies makes
it a challenge for the treatment of TNBC. Histone deacetylase inhibitors (HDACis)
are emerging as novel anti-tumor agents in many types of human cancers. In this
study, we found that I-7ab, a novel HDACi, inhibited the cell viability of TNBC
cells and induced the cell apoptosis. Mechanistically, I-7ab specifically
decreased the expression of HDAC3 and promoted the acetylation of p53 at both
Lys373 and Lys382 amino acids. The up-regulated acetylation of p53 promoted the
transcriptional activity of p53 and induced the expression of p21, which
consequently caused cell cycle arrest at G1 phase. Administration of I-7ab
inhibited the colony formation of TNBC cells. Collectively, these results
indicated I-7ab as a promising anti-cancer agent in the treatment of TNBC.
PMID- 29334666
TI - Effects of Berberine chloride on the liver of streptozotocin-induced diabetes in
albino Wistar rats.
AB - The goal of the present study is to evaluate the effect of Berberine chloride
(BC) on the liver of streptozotocin (STZ) induced diabetic rat. Diabetic rats
were treated with BC (50 mg/kg b.w) or glibenclamide (6 mg/kg b.w), daily for 45
days. After BC treatment in diabetic rats, there was a significant (P < 0.05)
decline in the levels of hepatic markers, lipid peroxidation markers such as
lipid hydroperoxides (LOOH) and thiobarbituric acid reactive substances (TBARS),
and pro-inflammatory mediators like tumor necrosis factor-alpha (TNF-alpha),
phosphorylated nuclear factor kappa-B-p65 (phospho-NF-kappaB p65), cyclooxygenase
(COX-2), nitric oxide synthase (iNOS) as well as pro-apoptotic mediators such as
Bax and cytochrome c. A significant (P < 0.05) increase in hexokinase, glucose-6
phosphate dehydrogenase, enzymatic antioxidants such as superoxide dismutase
(SOD), catalase (CAT) and glutathione peroxidase (GPx), and non-enzymatic
antioxidants such as glutathione (GSH), vitamin E and vitamin C, as well as anti
apoptotic protein Bcl-2 were observed in the liver of BC treated diabetic rats.
Thus, from these findings, it can be concluded that the administration of BC
notably recovered the liver from hyperglycemia induced antioxidant imbalance,
inflammation and apoptosis as well as rectified the imbalance in carbohydrate
metabolizing enzymes.
PMID- 29334667
TI - Lithium, a classic drug in psychiatry, improves nilotinib-mediated antileukemic
effects.
AB - Although Tyrosine kinase inhibitors (TKIs) that target Bcr-Abl play a key role in
Chronic Myeloid Leukemia (CML) therapy, they do not eradicate CML-initiating
cells, which lead to the emergence of drug resistance. Here we used the lithium,
a GSK-3 inhibitor, to attempt to potentiate the effects of nilotinib against
leukemia cells. For this purpose, a K562 leukemia cell line and bone marrow cells
from untreated Chronic Myeloid Leukemia (CML) patients, prior to any exposure to
TKIs, were used as a model. Our results demonstrated that the combination of
lithium + nilotinib (L + N) induced K562-cell death and cleaved caspase-3 when
compared to lithium or nilotinib alone, accompanied by GSK-3beta phosphorylation
and Bcr-Abl oncoprotein levels reduction. Interestingly, these events were
related to autophagy induction, expressed by increased LC3II protein levels in
the group treated with L + N. Furthermore, the clonogenic capacity of progenitor
cells from CML patients was drastically reduced by L + N, as well as lithium and
nilotinib when used separately. The number of cell aggregates (clusters), were
increased by all treatments (L + N, lithium, and nilotinib). This pioneering
research has demonstrated that lithium might be of therapeutic value when
targeting Bcr-Abl cells with nilotinib because it triggers cell death in addition
to exerting classical antiproliferative effects, opening new perspectives for
novel target and therapeutic approaches to eradicate CML.
PMID- 29334668
TI - Lidanpaidu prescription alleviates lipopolysaccharide-induced acute kidney injury
by suppressing the NF-kappaB signaling pathway.
AB - The Lidanpaidu Prescription (LDP), a hospital preparation, composed of Chinese
classical preparations, has been reported to have antiendotoxin, anticoagulant
and other effects. However, its therapeutic effect on lipopolysaccharide (LPS)
induced acute kidney injury (AKI) and the mechanisms remain unclear. Therefore,
we administered LPD pretreatment at different doses to examine the protective
effects and mechanisms in LPS-induced AKI in mice. The kidney injury induced by
LPS was assessed by histological examination. ELISA was used to detect the levels
of inflammatory cytokines. The mRNA expression of the inflammatory genes IKKbeta
and TNF-alpha in kidney tissues was assessed by RT-PCR. Finally, Western blot was
performed to assess the NF-kappaB signaling pathway related proteins, and the
nuclear translocation of NF-kB P65 was detected by immunofluorescence laser
confocal microscopy. The findings suggested that LDP significantly improved at 48
h animal survival (66.7%), compared with the LPS group (26.7%), determined by a
Kaplan-Meier analysis. LDP attenuated the kidney histopathological changes
induced by LPS and decreased the inflammatory cytokine levels in serum and renal
tissue. Moreover, LDP markedly inhibited the expression of inflammatory genes and
suppressed the activation of relevant proteins in the nucleus. In summary, these
findings suggest that LDP reduces LPS-induced AKI via a mechanism related to the
suppression of the NF-kappaB signaling pathway.
PMID- 29334669
TI - Anti-obesity effects of Clausena excavata in high-fat diet-induced obese mice.
AB - Clausena excavata (C. excavata) has been used as a traditional medicine for the
treatment of abdominal pain, enteritis, dysentery, and malaria. The present study
was designed to evaluate the effect of a 50% ethanol extract of C. excavata (ECE)
on weight loss, adipocyte size, and obesity-related biochemical parameters in
high-fat diet (HFD)-induced obese mice. After 6 weeks of HFD + ECE
administration, HFD-induced total fat, subcutaneous fat, and visceral fat were
evaluated by micro-computed tomography. The serum levels of triglyceride (TG),
total cholesterol (TCH), high-density lipoprotein (HDL) cholesterol, and low
density lipoprotein (LDL) cholesterol were evaluated with a biochemical analyzer,
and leptin and adiponectin levels in the serum were assessed via enzyme-linked
immunoassay (ELISA). Moreover, adipocyte size and lipid formation in the liver
were examined. We found that weight gain, epididymal fat pad weight, adipocyte
size, and lipid formation were markedly attenuated in the livers of HFD-induced
obese mice treated with ECE. Furthermore, TG, TCH, and leptin decreased in the
serum, whereas adiponectin increased. In conclusion, our data show that ECE has
potent anti-obesity activity in vivo and support the development of ECE as a
potential therapeutic agent for the treatment of obesity.
PMID- 29334670
TI - Genetic ablation of TRPV1 exacerbates pressure overload-induced cardiac
hypertrophy.
AB - Transient receptor potential vanilloid 1 (TRPV1) channels expressed in sensory
nerves may regulate vascular tone and cardiovascular function via their anti
inflammatory effects by releasing neuropeptide calcitonin gene-related peptide
(CGRP). Inflammation plays a role in the progression of cardiac hypertrophy and
TRPV1 activation may be key to cardiac inflammatory processes. The aim of this
study was to test the hypothesis that TRPV1 modulates inflammatory processes to
protect the heart from pressure overload-induced hypertrophy and inflammatory
responses. Trpv1 knockout (Trpv1-/-) and wild-type (WT) mice were subjected to
transverse aortic constriction (TAC) or sham operation. Four weeks after TAC, WT
and Trpv1-/- mice had developed left ventricular (LV) hypertrophy with increased
LV mass, fibrosis and infiltration of macrophages as well as increased secretion
of tumor necrosis factor alpha, interleukin-6 from cardiac tissue (all P < 0.05),
those were higher in Trpv1-/- than in WT mice with TAC (all P < 0.05). In
addition, decreases of LV ejection fraction and fractional shortening were
greater in Trpv1-/- than in WT mice (both P < 0.05). Moreover, atrial natriuretic
peptide level was greater in Trpv1-/- than in WT mice with TAC (P < 0.05).
Compared to sham control, TAC procedure significantly increased cardiac TRPV1
expression and CGRP release in WT mice (both P < 0.05), but not in Trpv1-/- mice.
These results demonstrate that Trpv1 gene deletion results in excessive
inflammation, exaggerates cardiac hypertrophy, and deteriorates cardiac function
after TAC, which may be due to abnormal cardiac remodeling and decreased CGRP in
the absence of TRPV1.
PMID- 29334671
TI - Glucosamine promotes osteoblast proliferation by modulating autophagy via the
mammalian target of rapamycin pathway.
AB - Glucosamine is effective in the treatment of osteoarthritis; however, its effect
on osteoporosis remains unclear. Decreased activity of osteoblasts is the main
cause of osteoporosis. Here, we examined the effects of glucosamine on
osteoblasts. The potential underlying mechanisms were explored. The results
showed that glucosamine had a biphasic effect on the viability of hFOB1.19
osteoblasts. At low concentrations (<0.6 mM), glucosamine induced hFOB1.19 cell
proliferation, whereas at high concentrations (>0.8 mM) it induced apoptosis. The
autophagy inhibitor 3-methyladenine (3-MA) was used to verify that glucosamine
modulated hFOB1.19 cell viability via autophagy. The induction of apoptosis by
high concentrations of glucosamine was significantly exacerbated by 3-MA, whereas
the promotion of cell proliferation by low concentrations of glucosamine was
significantly suppressed by 3-MA. Autophagy was examined by western blot
detection of autophagy-related proteins including LC3, Beclin-1, and SQSTM1/p62
and by immunofluorescence analysis of autophagosomes. Glucosamine activated
autophagy in a time- and concentration-dependent manner. Investigation of the
underlying mechanism showed that glucosamine inhibited the phosphorylation of m
TOR in a concentration-dependent manner within 48 h, and rapamycin significantly
inhibited the phosphorylation of m-TOR. These results demonstrated that
glucosamine promoted hFOB1.19 cell proliferation and increased autophagy by
inhibiting the m-TOR pathway, suggesting its potential as a therapeutic agent for
osteoporosis.
PMID- 29334672
TI - Oxidative and interactive challenge of cadmium and ocean acidification on the
smooth scallop Flexopecten glaber.
AB - Ocean acidification (OA) may affect sensitivity of marine organisms to metal
pollution modulating chemical bioavailability, bioaccumulation and biological
responsiveness of several cellular pathways. In this study, the smooth scallop
Flexopecten glaber was exposed to various combinations of reduced pH (pH/pCO2
7.4/~3000 MUatm) and Cd (20 MUg/L). The analyses on cadmium uptake were
integrated with those of a wide battery of biomarkers including metallothioneins,
single antioxidant defenses and total oxyradical scavenging capacity in digestive
gland and gills, lysosomal membrane stability and onset of genotoxic damage in
haemocytes. Reduced pH slightly increased concentration of Cd in scallop tissues,
but no effects were measured in terms of metallothioneins. Induction of some
antioxidants by Cd and/or low pH in the digestive gland was not reflected in
variations of the total oxyradical scavenging capacity, while the investigated
stressors caused a certain inhibition of antioxidants and reduction of the
scavenging capacity toward peroxyl radical in the gills. Lysosomal membrane
stability and onset of genotoxic damages showed high sensitivity with possible
synergistic effects of the investigated factors. The overall results suggest that
indirect effects of ocean acidification on metal accumulation and toxicity are
tissue-specific and modulate oxidative balance through different mechanisms.
PMID- 29334673
TI - Copper bioaccumulation and biokinetic modeling in marine herbivorous fish Siganus
oramin.
AB - Marine herbivorous fish directly consume macroalgae, which commonly accumulate
high levels of trace metals in polluted areas. We proposed that herbivorous fish
could be better candidates for biomonitoring marine metal pollution than
carnivorous fish. To date, the trophic transfer of Cu from macroalgae to marine
herbivorous fish is unclear. In this study, the kinetics of Cu bioaccumulation in
a widespread marine herbivorous fish, Siganus oramin, were investigated, and
biokinetic modeling was applied to estimate the Cu levels in the fish sampled
from different sites and seasons. The results showed that Cu accumulation in the
fish was linearly correlated to the dietary Cu levels in the different prey
species, which were proportional to the waterborne Cu concentrations. The Cu
found in the subcellular trophically available metal fraction (TAM) in the prey
contributed the largest proportion of accumulated Cu in S. oramin. The dietary
assimilation efficiencies (AEs) of Cu were 15.56 +/- 1.76%, 13.42 +/- 2.86%, and
21.36 +/- 1.47% for Ulva lactuca, Gracilaria lemaneiformis and Gracilaria gigas,
respectively. The calculated waterborne uptake rate constant (ku) of Cu was 0.023
+/- 0.011 L g-1 d-1, and the efflux rate constant (ke) was 0.055 +/- 0.021 d-1.
Dietary Cu accounted for 60%-75% of the body Cu in S. oramin, suggesting that
dietary uptake could be the primary route for Cu bioaccumulation in herbivorous
fish. The biokinetic model demonstrated that the Cu concentrations in the water
and fish presented a positive linear relationship, which was in line with our
field investigation along the coastal areas of South China. Therefore, we
suggested that S. oramin could be used as a biomonitoring organism for Cu
pollution in the marine environment. However, the heterogeneities between the
predicted levels and the measured levels of Cu implied that seasonal changes
should be taken into account to improve the accuracy of the model.
PMID- 29334674
TI - Relationship between jumping abilities and skeletal muscle architecture of lower
limbs in humans: Systematic review and meta-analysis.
AB - The aim of this study was to examine the influence of skeletal muscle
architecture (SMA) features measured by 2-D ultrasonography on jumping
performance in humans. A systematic review and meta-analysis was conducted,
registry number: CRD42016043602. The scientific literature was systematically
searched in eight databases, last run on March 14th, 2017. Cross-sectional
studies focused on the association between SMA features and vertical jumping
performance were selected. A random-effects model was used to analyze the
influence of lower-limb SMA and maximal jump height. A total of 11 studies were
included in the qualitative synthesis and 6 studies were selected for meta
analysis. 250 correlations were reviewed across studies. The vast majority were
either not statistically significant (185; 74%), weak or very weak (169; 68%) for
different jump modalities; counter-movement jump (CMJ), squat jump (SJ), and drop
jump. There was insufficient data to perform meta-analysis on muscles other than
vastus lateralis for CMJ and SJ. The meta-analyses did not yield any significant
association between vastus lateralis SMA and SJ height. Only a significant
overall association was shown between vastus lateralis thickness and CMJ height
(summary-r = 0.28; 95% confidence interval (CI) = -0.05 to 0.48; p = .059) for a
90% CI level. No differences were found between summary-r coefficients for SMA
parameters and jump height during both jumps (CMJ: chi2 = 2.43; df = 2; p =
.30; SJ: chi2 = 0.45; df = 2; p = .80) with a low heterogeneity ratio. Current
evidence does not suggest a great influence of lower-limb SMA on vertical jumping
performance in humans.
PMID- 29334675
TI - Effects of running retraining on biomechanical factors associated with lower limb
injury.
AB - Injury risk is an important concern for runners; however, limited evidence exists
regarding changes to injury risk following running style retraining.
Biomechanical factors, such as absolute peak free moment, knee abduction impulse,
peak foot eversion and foot eversion excursion, have been shown to predict lower
limb injury. The aim of this study was to assess the effects of Pose running
retraining on biomechanical factors associated with lower limb running injury.
Twenty uninjured recreational runners were pair-matched based on their five km
run time performance and randomly assigned to control (n = 10) and intervention
(three 2-h Pose running retraining sessions) groups (n = 10). Three dimensional
kinetic and kinematic data were collected from all participants running at
relative (REL: 1.5 km.h-1 below respiratory compensation point) and absolute
(ABS: 4.5 m.s-1) speeds. Biomechanical factors associated with lower limb injury,
as well as selected kinematic variables (to aid interpretation), were assessed.
Following a six-week, non-coached time-period, all assessments were repeated. No
changes to the biomechanical factors associated with lower limb injury examined
in this study were observed (P > .05). Intervention group participants (presented
as pre- and post-intervention respectively) exhibited an increased foot strike
index (REL speed: 21.79-42.66%; ESW = 4.73; P = .012 and ABS speed: 22.38-46.98%;
ESW = 2.83; P = .008), reduced take-off distance (REL speed: -0.35 to -0.32 m;
ESW = 0.75; P = .012), increased knee flexion at initial contact (REL speed:
14.11 to -18.50 degrees ; ESW = -0.88; P = .003), increased ankle dorsiflexion at
terminal stance (REL speed: -33.61 to -28.35 degrees ; ESW = 1.57; P = .036) and
reduced stance time (ABS speed: 0.21-0.19 s; ESW = -0.85; P = .018). Finally,
five km run time did not change (22:04-22:19 min; ESW = 0.07; P = .229). It was
concluded that following Pose running retraining, retrained participants adopted
a running style that was different to their normal style without changing
specific, biomechanical factors associated with lower limb injury or compromising
performance.
PMID- 29334676
TI - Statins in the treatment of COPD and asthma-where do we stand?
AB - Asthma and chronic obstructive pulmonary disease (COPD) are the two most
prevalent obstructive lung diseases that account for tremendous morbidity and
mortality throughout the world. These diseases have strong inflammatory
components, with multiple prior studies showing elevated levels of various
inflammatory markers and cells in those with COPD and asthma. Therefore, efforts
to target inflammation in management of these diseases are of great interest.
Statins, which define a class of drugs that are HMG-CoA inhibitors, are used to
decrease cholesterol levels and have also been described to have many pleotropic
effects that include anti-inflammatory and anti-oxidative properties. These
properties have led to multiple studies looking at the potential use of statins
in decreasing inflammation in many diseases, including COPD and asthma. This
review aims to address the current evidence behind the potential use of statins
in the treatment of asthma and COPD.
PMID- 29334677
TI - Utilizing journal club to facilitate critical thinking in pre-clinical medical
students.
PMID- 29334679
TI - The IL20 Genetic Polymorphism Is Associated with Altered Clinical Outcome in
Septic Shock.
AB - BACKGROUND: The IL10 family of genes includes crucial immune regulators. We
tested the hypothesis that single nucleotide polymorphisms (SNPs) in IL10, IL19,
IL20, and IL24 of the IL10 family gene cluster alter the clinical outcome of
septic shock. METHODS: Patients with septic shock (n = 1,193) were genotyped for
13 tag SNPs of IL10, IL19, IL20, and IL24. IL20 gene expression was measured in
genotyped lymphoblastoid cells in vitro. Cardiac surgical ICU patients (n = 981)
were genotyped for IL20 rs2981573 A/G. The primary outcome variable was 28-day
mortality. RESULTS: Patients with the G allele of IL20 rs2981573 had a
significantly increased hazard of death over the 28-day period compared to
patients with the A allele in the septic shock cohort (adjusted hazard ratio
1.27; 95% confidence interval 1.10-1.47; p = 8.0 * 10-4). Patients with the GG
genotype had more organ dysfunction (p < 0.05). The GG genotype was associated
with increased IL20 gene expression in stimulated lymphoblastoid cells in vitro
(p < 0.05). The cardiac surgical ICU patients with the GG genotype had an
increased length of ICU stay (p = 0.032). CONCLUSIONS: The GG genotype of IL20
rs2981573 SNP was associated with increased IL20 gene expression and increased
adverse outcomes in patients with septic shock and following cardiac surgery.
PMID- 29334678
TI - Genome Evolution Analysis of Recurrent Testicular Malignant Mesothelioma by Whole
Genome Sequencing.
AB - BACKGROUND/AIMS: Malignant mesothelioma of the tunica vaginalis testis is a rare
and lethal disease. The genomic characteristics and genetic changes of tumor
cells during the progression of this disease are unknown. METHODS: we performed
whole-genome sequencing of four successive tumor samples derived from surgery and
a blood sample in a single patient. RESULTS: All tumors were found to have
significant C-to-T and T-to-C mutations, and amplification of copy number in
chromosomes 1 and 12 were notified in all tumor samples. Subclone analysis
revealed a parallel evolution of the tumor in this patient. We also identified
some mutations in mesothelioma-associated genes such as KIF25, AHNAK, and PRDM2.
CONCLUSIONS: The results showed a comprehensive genomic change in malignant
mesothelioma of the tunica vaginalis testis and provide a better understanding of
the clonal evolution during tumor recurrence and metastasis.
PMID- 29334680
TI - Blood Pressure Variability in Acute Ischemic Stroke: Influence of Infarct
Location in the Insular Cortex.
AB - BACKGROUND: The aim of this study was to elucidate the influence of insular
infarction on blood pressure (BP) variability and outcomes according to the
region of the insular cortex affected. METHODS: A total of 90 patients diagnosed
with acute unilateral ischemic stroke were registered. The BP variability was
calculated over 24 h after admission (hyperacute) and for 2-3 days after
admission (acute). Patients were classified into groups of right and left, and
then right anterior, right posterior, left anterior, and left posterior insular
infarction. RESULTS: Patients with insular infarction showed a significantly
larger infarct volume, higher modified Rankin scale scores, and lower SD and
coefficient of variation (CV) of -systolic BP in the hyperacute phase than shown
by patients without insular infarction (p < 0.01, p < 0.01, p = 0.02, and p =
0.03, respectively). The SD and CV of systolic BP in the hyperacute phase showed
significant differences among the 3 groups with right insular infarction, with
left insular infarction, and without insular infarction (p < 0.05 and p < 0.05,
respectively). There was a tendency for the systolic BP variability to be lower
in patients with right anterior insular infarction than in patients with infarcts
in other areas. CONCLUSION: The right insular cortex, especially the anterior
part, might be a hub for autonomic nervous regulation.
PMID- 29334681
TI - Is There Any Common Pathophysiology between Central Nervous System Lupus and
Parkinson's Disease?
PMID- 29334682
TI - Body Mass Index and Plasma P-Selectin before Coronary Stenting Predict High
Residual Platelet Reactivity at 6 Months on Dual Antiplatelet Therapy.
AB - BACKGROUND: High residual platelet reactivity (HRPR) during dual antiplatelet
therapy (DAPT) may impact clinical outcomes following percutaneous coronary
interventions (PCI). However, whether any biomarkers assessed before PCI at DAPT
loading may predict delayed maintenance HRPR is not clear. OBJECTIVE: The aim of
this study was to determine whether conventional clinical or laboratory indices
at loading before stenting may predict HRPR at 6 months of maintenance DAPT.
METHODS: The study was designed on a single-center prospective cohort, and
included 94 pre-PCI patients. All patients underwent elective PCI with drug
eluting stent implantation, and received DAPT with aspirin and clopidogrel.
Platelet reactivity was assessed with 5 MUmol/L of adenosine diphosphate-induced
light transmission aggregometry before PCI, but after 24 h of DAPT loading, and
repeated at 6 months. Baseline clinical characteristics, CYP2C19 polymorphism, C
reactive protein, soluble P-selectin, CD40L, interleukin-6, PAI-1 levels, and von
Willebrand factor activity were analyzed. RESULTS: The incidence (light
transmission aggregometry <50%) of prestent HRPR was 16%. By univariate
regression, body mass index (BMI; p = 0.02), total cholesterol (p = 0.01), low
density lipoproteins (p = 0.004), CYP2C19*2 allele carriage (p = 0.006), soluble
P-selectin (p = 0.009), and von Willebrand factor (p = 0.04) were linked to
future HRPR. However, multivariate regression analysis suggested that only BMI
and P-selectin were independent predictors of HRPR. CONCLUSIONS: Platelet
reactivity before elective stenting is associated with numerous biomarkers;
however, only BMI and soluble P-selectin were independent predictors of future
HRPR during maintenance-phase DAPT. This may be important for future tailored
antiplatelet strategies in patients with metabolic syndrome and diabetics.
PMID- 29334683
TI - Epigenetic Silencing of the MLH1 Promoter in Relation to the Development of
Gastric Cancer and its use as a Biomarker for Patients with Microsatellite
Instability: a Systematic Analysis.
AB - BACKGROUND/AIMS: Human mutL homolog 1 (MLH1) promoter methylation was reported in
gastric cancer (GC). This study determined the clinicopathological, prognostic,
and diagnostic effects of MLH1 promoter methylation in GC. METHODS: The combined
odds ratio (OR) or hazard ratio (HR) and their corresponding 95% confidence
intervals (95% CI) were calculated. The pooled sensitivity, specificity, and area
under the curve (AUC) were analyzed. RESULTS: A total of 4654 GC patients and
3669 non-malignant controls were identified in this systematic analysis. MLH1
promoter methylation was significantly higher in GC samples than in gastric
adenomas, chronic gastritis, adjacent tissues, normal gastric mucosa, and normal
healthy blood samples, but it exhibited a similar frequency in GC vs. intestinal
metaplasia and dysplasia samples. MLH1 promoter methylation correlated with age
and microsatellite instability (MSI), but it was not associated with gender, H.
pylori infection, smoking, drinking behaviors, pathological histology, tumor
differentiation, clinical stage, lymph node status, distant metastasis, or
overall survival of GC. MLH1 promoter methylation exhibited a poor sensitivity
value (< 0.5) in patients with GC compared with adjacent tissues, gastric
adenomas, chronic gastritis, normal gastric mucosa, and normal healthy blood
samples. The pooled sensitivity, specificity, and AUC of MLH1 promoter
methylation in GC with MSI vs. GC with microsatellite stability (MSS) samples
were 0.64, 0.96, and 0.90, respectively. CONCLUSIONS: Our results suggest that
the detection of MLH1 promoter methylation may be a potential prognostic
biomarker for GC patients with MSI.
PMID- 29334684
TI - Aberrant Connectivity in Mild Cognitive Impairment and Alzheimer Disease Revealed
by Multimodal Neuroimaging Data.
AB - BACKGROUND: Making use of multimodal data simultaneously to understand the neural
mechanism of mild cognitive impairment (MCI) has been in the focus nowadays. The
simultaneous use of multimodal data can take advantage of each modality which may
only provide the view of one specific aspect of the brain. OBJECTIVE: To this
end, the present study used structural magnetic resonance imaging (sMRI),
fluorodeoxyglucose positron emission tomography (FDG-PET) and florbetapir PET to
reveal the integrated brain network between MCI and normal controls (NCs).
METHODS: In this study, 116 MCI, 116 NC and 116 Alzheimer disease (AD) subjects
from the Alzheimer's Disease Neuroimaging Initiative were included for the
evaluation of the brain covariance graphic model. Sparse inverse covariance
estimation was utilized to get the graphic model. RESULTS: The connections among
different brain regions were quite different between NC and MCI or between MCI
and AD subjects (p < 0.01). The number of connections, which were represented by
the covariance among different brain regions in the graphic model, decreased from
NC to MCI and then AD, especially in the temporal lobe, occipital-parietal lobe
and parietal-temporal lobe. CONCLUSION: These findings are good evidence to
reveal the difference between MCI or AD and NC, and enhance the understanding of
MCI.
PMID- 29334685
TI - Observation of a phononic quadrupole topological insulator.
AB - The modern theory of charge polarization in solids is based on a generalization
of Berry's phase. The possibility of the quantization of this phase arising from
parallel transport in momentum space is essential to our understanding of systems
with topological band structures. Although based on the concept of charge
polarization, this same theory can also be used to characterize the Bloch bands
of neutral bosonic systems such as photonic or phononic crystals. The theory of
this quantized polarization has recently been extended from the dipole moment to
higher multipole moments. In particular, a two-dimensional quantized quadrupole
insulator is predicted to have gapped yet topological one-dimensional edge modes,
which stabilize zero-dimensional in-gap corner states. However, such a state of
matter has not previously been observed experimentally. Here we report
measurements of a phononic quadrupole topological insulator. We experimentally
characterize the bulk, edge and corner physics of a mechanical metamaterial (a
material with tailored mechanical properties) and find the predicted gapped edge
and in-gap corner states. We corroborate our findings by comparing the mechanical
properties of a topologically non-trivial system to samples in other phases that
are predicted by the quadrupole theory. These topological corner states are an
important stepping stone to the experimental realization of topologically
protected wave guides in higher dimensions, and thereby open up a new path for
the design of metamaterials.
PMID- 29334686
TI - Fat Mass and Obesity-Related Gene Variants rs9939609 and rs7185735 are Associated
with Second-Generation Antipsychotic-Induced Weight Gain.
AB - INTRODUCTION: Weight gain is a limiting and frequent adverse effect of second
generation antipsychotic therapy. Identifying genetic risk factors would
significantly improve pharmacotherapy. METHODS: We focused on rs7185735 and
rs9939609, 2 common single nucleotide polymorphisms of the fat mass and obesity
associated (FTO) gene reported to be associated with obesity. Three-hundred fifty
Caucasian inpatients were included in a naturalistic study. RESULTS: After 4
weeks of treatment, we did not observe any significant association of
polymorphisms with weight change in the whole study population (p>0.05). In a
subpopulation without additional weight-inducing comedication (n=178), G-allele
carriers of rs7185735 gained 3.4 times more weight (1.69 kg+/-3.1 kg, p=0.019)
than AA genotypes (0.49 kg+/-3.1 kg). A-allele carriers of rs9939609 gained 3.1
times more weight (1.65 kg+/-3.1 kg, p=0.029) than TT genotypes (0.54 kg+/-3.2
kg). DISCUSSION: Our findings confirm the role of the FTO gene as a high
potential risk factor for obesity and indicate a value for predicting a weight
gain induced by second-generation antipsychotics. Further, we detected an
additive effect of FTO rs7185735 and MC4R rs17782313.
PMID- 29334687
TI - Cognitive Deficits in Methamphetamine Users: How Strong is The Evidence?
AB - Methamphetamine use has spread in many European countries and the United States.
The current review provides a summary and critical analysis of research on
cognitive deficits associated with methamphetamine, also known as "crystal meth."
The literature search performed for this review led us to the hypothesis that
methamphetamine use is associated with persistent changes in brain metabolism
that result in various impairments, such as deficits in memory, attention, and
concentration. The dopaminergic system in particular seems to be affected. Some
studies indicate that cognitive impairments may improve when users become
abstinent, but results of other studies are conflicting. This review discusses
these findings and the consequences for the development of a specific addiction
treatment for methamphetamine.
PMID- 29334688
TI - [Guideline for the Diagnosis and Treatment of Asthma - Guideline of the German
Respiratory Society and the German Atemwegsliga in Cooperation with the
Paediatric Respiratory Society and the Austrian Society of Pneumology].
PMID- 29334689
TI - 'Stick with your own kind, or hang with the locals?' Implications of shoaling
strategy for tropical reef fish on a range-expansion frontline.
AB - Range shifts of tropical marine species to temperate latitudes are predicted to
increase as a consequence of climate change. To date, the research focus on
climate-mediated range shifts has been predominately dealt with the physiological
capacity of tropical species to cope with the thermal challenges imposed by
temperate latitudes. Behavioural traits of individuals in the novel temperate
environment have not previously been investigated, however, they are also likely
to play a key role in determining the establishment success of individual species
at the range-expansion forefront. The aim of this study was to investigate the
effect of shoaling strategy on the performance of juvenile tropical reef fishes
that recruit annually to temperate waters off the south east coast of Australia.
Specifically, we compared body-size distributions and the seasonal decline in
abundance through time of juvenile tropical fishes that shoaled with native
temperate species ('mixed' shoals) to those that shoaled only with conspecifics
(as would be the case in their tropical range). We found that shoaling with
temperate native species benefitted juvenile tropical reef fishes, with
individuals in 'mixed' shoals attaining larger body-sizes over the season than
those in 'tropical-only' shoals. This benefit in terms of population body-size
distributions was accompanied by greater social cohesion of 'mixed' shoals across
the season. Our results highlight the impact that sociality and behavioural
plasticity are likely to play in determining the impact on native fish
communities of climate-induced range expansion of coral reef fishes.
PMID- 29334690
TI - Intestinal metabolism of Polygonum cuspidatum in vitro and in vivo.
AB - Rhizoma et Radix Polygoni Cuspidati (RRPC) is commonly prescribed for the
treatment of amenorrhea, arthralgia, jaundice and abscess in traditional Chinese
medicine. Previous pharmacological studies have indicated that polyphenols are
the main pharmacological active ingredients in RRPC. Meanwhile, the poor
bioavailability of polyphenols in RRPC implies that those components are probably
metabolized by intestinal bacteria before absorption. However, there is rather
limited information about RRPC''s metabolites produced by intestinal bacteria and
the intestinal absorbed constituents. In the present study, the metabolites were
characterized after the aqueous extract of RRPC was incubated with the crude
enzyme of human intestinal bacteria in vitro. The metabolic characteristics of
glycosides in RRPC were figured out by comparing the metabolic profiles of emodin
8-O-beta-d-glucopyranoside and polydatin between aqueous extract of RRPC and
equivalent amounts of these two glycosides. The transitional constituents
absorbed into blood were investigated in rats via intraduodental administration
and portal vein intubation. A total of 38 prototype components and 43 metabolites
were detected and characterized in vivo. The overall results demonstrated that
the intestinal bacteria played an important role in the metabolism of RRPC, and
the main metabolic pathways were hydrolysis in vitro, glucuronidation and
sulfation in vivo.
PMID- 29334691
TI - A meta-analysis of the effects of bariatric surgery on fracture risk.
AB - Bariatric surgery effectively treats morbid obesity. However, the negative effect
of this surgery on the bone is concerning. The aim of this meta-analysis was to
investigate the fracture risk associated with bariatric surgery in morbidly obese
subjects. Relevant studies published from database inception to September 2017
were identified in PubMed, Embase and the Cochrane Library. The Newcastle-Ottawa
Scale was used to evaluate the quality of the observational studies, and the
Jadad score evaluated randomized controlled trials. Among the 1003 studies
initially identified, five observational trials and one randomized controlled
trial were eligible for inclusion. All studies included in the meta-analysis were
considered high quality. Risk for any type of fracture was higher in the surgical
group than in the non-surgical group (risk ratio [RR] 1.29, 95% confidence
interval [CI] 1.18-1.42). After surgery, the fracture risk in non-vertebral sites
was significantly increased, especially in the upper limbs (RR 1.42, 95% CI 1.08
1.87; and RR 1.68, 95% CI 1.15-2.45). Compared with those with restrictive
procedures, subjects who underwent mixed restrictive and malabsorptive procedures
tended to have an increased fracture risk (RR 1.54, 95% CI 0.96-2.46). To
conclude, bariatric surgery is associated with an increased risk of total and non
vertebral fractures, especially in the upper limbs.
PMID- 29334692
TI - Body mass index, abdominal adiposity, weight gain and risk of developing
hypertension: a systematic review and dose-response meta-analysis of more than
2.3 million participants.
AB - OBJECTIVE: This study aimed to test the association between anthropometric
measures and risk of developing hypertension. METHODS: We did a systematic search
using PubMed and Scopus, from inception up to January 2017. Prospective cohort
studies reporting the risk estimates of hypertension for three or more
quantitative categories of indices of general and abdominal adiposity were
included. Summary relative risks were calculated using random-effects models.
RESULTS: Fifty-seven prospective cohort studies were included. Summary relative
risks were 1.49 (95% confidence interval [CI]: 1.41, 1.58; I2 = 97.4%, n = 50)
for a five-unit increment in body mass index, 1.27 (95%CI: 1.15, 1.39; I2 =
95.0%, n = 14) for a 10-cm increment in waist circumference, 1.16 (95%CI: 1.09,
1.23; I2 = 77.8%, n = 5) for weight gain equal to a one-unit increment in BMI,
and 1.37 (95%CI: 1.24, 1.51; I2 = 76.4%, n = 8) and 1.74 (95%CI: 1.35, 2.13; I2
= 58.9%, n = 4) for a 0.1-unit increment in waist-to-hip ratio and waist-to
height ratio, respectively. The risk of hypertension increased continuously with
increasing all anthropometric measures, and also along with weight gain.
CONCLUSION: Being as lean as possible within the normal body mass index range may
be the best suggestion in relation to primary prevention of hypertension.
PMID- 29334693
TI - The frequency of family meals and nutritional health in children: a meta
analysis.
AB - Findings on the relationship between family meal frequency and children's
nutritional health are inconsistent. The reasons for these mixed results have to
date remained largely unexplored. This systematic review and meta-analysis of 57
studies (203,706 participants) examines (i) the relationship between family meal
frequency and various nutritional health outcomes and (ii) two potential
explanations for the inconsistent findings: sociodemographic characteristics and
mealtime characteristics. Separate meta-analyses revealed significant
associations between higher family meal frequency and better overall diet quality
(r = 0.13), more healthy diet (r = 0.10), less unhealthy diet (r = -0.04) and
lower body mass index, BMI (r = -0.05). Child's age, country, number of family
members present at meals and meal type (i.e. breakfast, lunch or dinner) did not
moderate the relationship of meal frequency with healthy diet, unhealthy diet or
BMI. Socioeconomic status only moderated the relationship with BMI. The findings
show a significant relationship between frequent family meals and better
nutritional health - in younger and older children, across countries and
socioeconomic groups, and for meals taken with the whole family vs. one parent.
Building on these findings, research can now target the causal direction of the
relationship between family meal frequency and nutritional health.
PMID- 29334694
TI - Home alone: a systematic review and meta-analysis on the effects of individual
housing on body weight, food intake and visceral fat mass in rodents.
AB - Rats and mice are widely used to study environmental effects on psychological and
metabolic health. Study designs differ widely and are often characterized by
varying (social) housing conditions. In itself, housing has a profound influence
on physiology and behaviour of rodents, affecting energy balance and sustainable
metabolic health. However, evidence for potential long-term consequences of
individual versus social housing on body weight and metabolic phenotype is
inconsistent. We conducted a systematic literature review and meta-analyses
assessing effects of individual versus social housing of rats and mice, living
under well-accepted laboratory conditions, on measures of metabolic health,
including body weight, food intake and visceral adipose tissue mass. Seventy-one
studies were included in this review; 59 were included in the meta-analysis.
Whilst housing did not affect body weight, both food intake and visceral adipose
tissue mass were significantly higher in individually compared with socially
housed animals. A combination of emotional stress and lack of social
thermoregulation likely contributed to these effects. Increased awareness of
consequences and improved specifications of housing conditions are necessary to
accurately evaluate efficacy of drugs, diets or other interventions on metabolic
and other health outcomes because housing conditions are rarely considered as
possible moderators of reported outcomes.
PMID- 29334695
TI - Complex interplay among adiposity, insulin resistance and bone health.
AB - Obesity and osteoporosis are common public health problems. Paradoxically, while
obesity is associated with higher bone density, type 2 diabetic obese individuals
have an increased fracture risk. Although obesity and insulin resistance co
exist, some obese individuals remain insulin-sensitive. We suggest that the
apparent paradox relating obesity, bone density and fracture risk in type 2
diabetes may be at least partly influenced by differences in bone strength and
quality between insulin-resistant and insulin-sensitive obese individuals. In
this review, we focus on the complex interplay between, adiposity, insulin
resistance and osteoporotic fracture risk and suggest that this is an important
area of study that has implications for individually tailored and targeted
treatment to prevent osteoporotic fracture in obese type 2 diabetic individuals.
PMID- 29334696
TI - Mast cells participate in chronic low-grade inflammation within adipose tissue.
AB - Obesity is reckoned as one of the civilization diseases, posing a considerable
global health issue. Evidence points towards a contribution of multitude immune
cell populations in obesity pathomechanism and the development of chronic low
grade inflammation in the expanded adipose tissue. Notably, adipose tissue is a
reservoir of mast cells which number in individuals with obesity particularly
increased. Some of them tend to degranulation what generate secretion of strong
pro-inflammatory and regulatory mediators, as well as cytokines/chemokines.
Several lines of evidence suggest that mast cells are strictly associated with
pro-inflammatory status in adipose tissue by their indirect impact on immune cell
attraction and activation. Furthermore, mast cells affect adipose tissue
remodelling and fibrosis by adipocyte differentiation, fibroblast proliferation
and enhancing extracellular matrix proteins expression. This review will
summarize current knowledge on mast cell features and their role in the
development of chronic low-grade inflammation within adipose tissue.
PMID- 29334697
TI - Sepsis-induced activation of endogenous GLP-1 system is enhanced in type 2
diabetes.
AB - BACKGROUND: High levels of circulating GLP-1 are associated with severity of
sepsis in critically ill nondiabetic patients. Whether patients with type 2
diabetes (T2D) display different activation of the endogenous GLP-1 system during
sepsis and whether it is affected by diabetes-related metabolic parameters are
not known. METHODS: Serum levels of GLP-1 (total and active forms) and its
inhibitor enzyme sDPP-4 were determined by ELISA on admission and after 2 to 4
days in 37 sepsis patients with (n = 13) and without T2D (n = 24) and compared to
normal healthy controls (n = 25). Correlations between GLP-1 system activation
and clinical, inflammatory, and diabetes-related metabolic parameters were
performed. RESULTS: A 5-fold (P < .001) and 2-fold (P < .05) increase in active
and total GLP-1 levels, respectively, were found on admission as compared to
controls. At 2 to 4 days from admission, the level of active GLP-1 forms in
surviving patients were decreased significantly (P < .005), and positively
correlated with inflammatory marker CRP (r = 0.33, P = .05). T2D survivors
displayed a similar but more enhanced pattern of GLP-1 response than nondiabetic
survivors. Nonsurvivors demonstrate an early extreme increase of both total and
active GLP-1 forms, 9.5-fold and 5-fold, respectively (P < .05). The initial and
late levels of circulating GLP-1 inhibitory enzyme sDPP-4 were twice lower in all
studied groups (P < .001), compared with healthy controls. CONCLUSIONS: Taken
together, these data indicate that endogenous GLP-1 system is activated during
sepsis. Patients with T2D display an enhanced and prolonged activation as
compared to nondiabetic patients. Extreme early increased GLP-1 levels during
sepsis indicate poor prognosis.
PMID- 29334698
TI - Endoscopic ultrasound and the liver: current applications and beyond.
AB - The diagnosis and management of many gastrointestinal conditions has been
augmented by the development of endoscopic ultrasound. Its role in the diagnosis
and management of liver disease has been somewhat limited, but with the rapid
development of therapeutic advancements it has quickly emerged as a useful tool
in the management of complex hepatic conditions. This includes its use in the
management of complications of portal hypertension as well as its use in liver
lesions and cancer. In this paper, we review case studies, case series and trials
for hepatic applications of endoscopic ultrasound to provide an overview of its
utilization in this field and demonstrating its more novel applications for
future use.
PMID- 29334699
TI - Tokyo Guidelines 2018: updated Tokyo Guidelines for the management of acute
cholangitis/acute cholecystitis.
PMID- 29334700
TI - [Hygiene and health: current situation and prospective].
PMID- 29334701
TI - [Pay attention to the nutrition and health of pregnancy women with advanced age].
PMID- 29334702
TI - [Prevalence of calf muscle cramps and influencing factors for pregnant women in
China during 2010-2012].
AB - Objective: To investigate the prevalence of calf muscle cramps and possible
influencing factors for pregnant women in China. Methods: Using a multi-stage
stratified probability proportional to size cluster randomization sampling method
during 2010-2012. A total of 3 582 pregnant women were investigated at 150
counties from 31 provinces in China mainland. Information on calf muscle cramps,
demographic socio-economic status, pregnancy information, and the physical
activities was collected through questionnaires. The semi-quantitative food
frequency questionnaire (FFQ) was used to collect food intake of pregnant women.
Dynamic cluster analysis was used to assess dietary pattern. Multiple logistic
regression was used to investigate the possible influencing factors for calf
muscle cramps. Results: The prevalence of calf muscle cramps was 32.9% (1 180/3
582) in Chinese pregnant women, which was 11.6% (87/748), 28.2% (420/1 492), and
50.2% (673/1 342), respectively, during the first, second and third trimester.
There were significant differences between them (chi(2)=349.16, P<0.001). Dietary
patterns of the pregnant women were classified into three groups, which called
relatively balanced pattern, high vegetables and fruits pattern, and high dairy
pattern. Among the three groups, the prevalence of calf muscle cramps was 32.0%
(952/2 971), 37.2% (186/500), and 37.8% (42/111), with significant differences
(chi(2)=6.39, P=0.041). The OR (95%CI) values of calf muscle cramps in the second
and third trimester was 2.96 (2.28-3.83), and 8.02 (6.16-10.44), respectively,
comparing with the first trimester. The OR (95%CI) values of calf muscle cramps
in the women taking calcium before pregnant was 1.45 (1.19-1.76), comparing with
the one who was not taken. The OR (95%CI) values of calf muscle cramps in the
women who had been diagnosed by pregnancy-induced hypertension was 5.76 (2.06
16.12), comparing with the one who had not been diagnosed. The OR (95%CI) values
of calf muscle cramps in the high vegetables and fruits pattern and high dairy
pattern was 1.13 (0.91-1.41), and 1.18 (0.76-1.81), respectively, comparing with
the relatively balanced pattern. Conclusion: The prevalence of calf muscle cramps
was relatively high in Chinese pregnant women, which was significantly different
among three trimesters. The residential areas, occupation, and pregnancy-induced
hypertension might be related to the prevalence of calf muscle cramps. However,
there was no significant difference among different dietary patterns.
PMID- 29334703
TI - [The influencing factors of anemia for pregnant women between 2010-2012 in
China].
AB - Objective: To investigate the prevalence of anemia and related risk factors for
pregnant women in China. Method: Based on Chinese National Nutrition and Health
Surveillance 2010-2012, a total of 3 501 pregnant women were investigated from
150 counties of 31 provinces, municipalities and autonomous regions in China,
using a multi-stage stratified cluster randomization sampling method. General
information of pregnant women, health status, and food intake during the
gestation, was collected through a questionnaire investigation. 6 ml fasting
venous blood was collected for the determination of hemoglobin concentration.
Data were analyzed using multiple logistic regression to investigate the
prevalence of anemia and the related influencing factors. Results: The 605 of 3
501 pregnant women had anemia. The prevalence of anemia was 17.2%; and mild
anemia accounted for about 61.0% (369/605). Compared with the pregnant women
living in the large cities, the OR (95%CI) of those living in the poor rural
areas was 1.46 (1.08-1.98). Compared with the pregnant women living in the south
area of China, the OR (95%CI) of those living in the north area of China was 1.39
(1.15-1.68); Compared with the pregnant women in the first trimester, the OR
(95%CI) of those in the second trimester and the third trimester were 1.79 (1.33
2.43) and 2.11 (1.56-2.85), respectively. The OR (95%CI) of pregnant women who
had used folic acid supplementation within the 6 months prior to gestation was
0.76 (0.63-0.93) compared with those who had not used. Conclusion: From 2010 to
2012, the epidemic characteristics of anemia was mild for the pregnant women in
China, and pregnant women residential areas, periods of pregnancy and whether to
take folic acid were related to anemia.
PMID- 29334704
TI - [Status and related factors for gestational weight gain of Chinese pregnant women
during 2010-2012].
AB - Objective: To examine the status and related factors for gestational weight gain
of Chinese pregnant women at different trimesters in 2010-2012. Methods:
Participants were from Chinese National Nutrition and Health Surveillance in 2010
2012. Using a multi-stage stratified cluster random sampling method, we recruited
2 805 singleton pregnant women with gestational age 13 weeks or more from 31
provinces of China. A standard questionnaire was used to collect general
information and pre-pregnancy weight; body weight and height of pregnant women
were measured using a unified weighing scale and stadiometer, dietary intake
during the previous year was collected using a food frequency questionnaire. A
multiple logistic regression was used to analyze potential factors associated
with appropriate gestational weight gain. Results: Among 2 805 pregnant women, 1
441 were in the second (13-27 weeks) and 1 364 in the third trimesters (>=28
weeks) . In the 2(nd) trimester, 229 cases (15.9%), 440 cases (30.5%) and 772
cases (53.6%) were insufficient gestational weight gain, appropriate gestational
weight gain and excessive gestational weight gain respectively. So were 256 cases
(18.8%), 474 cases (34.8%), 634 cases (46.5%) in the 3(rd) trimester
respectively. In the multivariate unconditional logistic model, less fruit intake
was associated with insufficient weight gain for women in the 2(nd) trimester (OR
(95%CI): 1.58 (1.06-2.34)). Pregnant women with Han ethnicity who live in the
small/medium city had lower risk of insufficient weight gain in the 3(rd)
trimester (OR (95%CI): 0.58 (0.34-0.98)). Those pregnant women with physical
activity <1 hour/day had a higher risk of excessive weight gain (OR (95%CI): 1.33
(1.02-1.73)). Conclusion: The prevalence of appropriate gestational weight gain
was low in China. Our study suggests that pregnant weight gain is associated with
fruit intake, types of residential area and physical activity.
PMID- 29334705
TI - [Gestational weight gain and optimal ranges in Chinese mothers giving singleton
and full-term births in 2013].
AB - Objective: To analyze the status of gestational weight gain (GWG) among Chinese
mothers who gave singleton and full-term births, and to look at optimal GWG
ranges. Methods: In 2013, using the multi-stage stratified and population
proportional cluster sampling method, we investigated 8 323 mother-child pairs at
their 0-24 months postpartum from 55 counties (cities/districts) of 30 provinces
(except Tibet) in mainland China. Questionnaire was used to collect data on body
weight before pregnancy and delivery, diseases during gestation, hemorrhage or
not at postpartum, child birth weight and length, and other information about
pregnant outcomes. We measured mother's body weight and height, and child's body
weight and length. Based on 'Chinese Adult Body Weight Standard', we divided
mothers into four groups according to their body weight before pregnancy: low
weight (BMI<18.5 kg/m(2)), normal weight (BMI 18.5-23.9 kg/m(2)), overweight (BMI
24.0-27.9 kg/m(2)) and obesity (BMI>=28.0 kg/m(2)). The status of GWG was
assessed by IOM optimal GWG guidelines. Chinese optimal GWG ranges were
calculated according to the association of GWG with pregnant outcomes and
anthropometry of mothers and children, and according to P25-P75 of GWG among
mothers who had good pregnant outcomes and good anthropometry, and whose children
had good anthropometry. The status of GWG was assessed by the new optimal ranges.
Results: P50 (P25-P75) of GWG among the 8 323 mothers was 15.0 (10.0-19.0) kg.
According to the proposed optimal GWG ranges of IOM, the proportions of
inadequate, optimal and excessive GWG accounted for 27.2% (2 263 mothers), 36.2%
(3 016 mothers) and 36.6% (3 044 mothers). The optimal GWG ranges for low weight,
normal weight, overweight and obesity were 11.5-18.0, 10.0-15.0, 8.0-14.0 and 5.0
11.5 kg. Based on these optimal GWG ranges established in this study, the rates
of inadequate, optimal and excessive GWG were 15.7% (1 303 mothers), 45.0% (3 744
mothers) and 39.3% (3 276 mothers), and these rates were significantly different
from that defined by the IOM standards (chi2=345.36, P<0.001). Conclusion: The
median of GWG among Chinese mothers is 15.0 kg, which is at a relatively higher
level. This study suggests the optimal GWG ranges for Chinese women who give
singleton and full-term babies, which appears lower than IOM's.
PMID- 29334706
TI - [Analysis of mothers' acceptance of HPV vaccination of adolescent girls in
Xiamen].
AB - Objective: To survey the mothers' acceptance of the HPV vaccination for their
adolescent girls in Xiamen and to explore the influencing factors. Methods:
Mothers of adolescent girls were selected by multistage cluster random sampling.
Data of demography of the mothers and girls, the knowledge and attitude of
cervical cancer and HPV vaccine of the mothers were collected. The influencing
factors of mothers' attitudes were analyzed with univariate and multivariate
logistic regression. Results: A total of 2 307 mothers were selected. The average
age of mothers was (38.0+/-4.7) years. 13.1% (300) of the mothers had a family
history of malignant tumor. The mothers' acceptance for vaccinating girls was
61.9% (1 428). The awareness rates of HPV and HPV vaccine were 42.5% (980) and
21.4% (493), respectively. Mothers who had family history of cancer (OR=1.36,
95%CI:1.02-1.82) showed a greater willingness to vaccinate their girls than the
mothers who had not. Mothers who had knowledge of HPV (OR=1.32, 95%CI:1.08-1.62)
and HPV (OR=2.03, 95%CI:1.56-2.66) vaccines showed a greater willingness to
vaccinate their girls than the mothers who had not. Conclusion: The mothers'
acceptance to vaccinate adolescent girls against cervical cancer needs to be
raised, especially for the mothers who had not family history of cancer, no
knowledge of HPV and HPV vaccines.
PMID- 29334708
TI - [Analysis of measles immunity level and serological susceptibility among Yunnan
residents aged >=20 years].
AB - Objective: To evaluate the population immunity to measles and explore the factors
associated with measles susceptibility in Yunnan residents aged >=20 years.
Methods: 2 689 residents aged >=20 years were selected by multistage stratified
systematic randomized sampling in 252 villages of 42 counties in Yunnan Province
between June and September in 2015. Each subject was surveyed by the same
questionnaire, including general information, measles contained vaccine history,
measles history, and 5 ml blood sample of each subject was collected. Serum IgG
antibodies against measles virus were measured by ELISA. Positive was defined as
the antibody concentration >=250 mU/ml, and negative as <250 mU/ml. Non
conditional logistic regression model was used analyze the factors associated
with measles susceptibility in adults. Results: Among 2 689 subjects, 1 214 were
males (45.15%), and the overall positive rate of measles IgG antibody was 89.77%.
Compared with subjects from the region where economic development was low,
subjects from the region where economic development was moderate were likely to
be susceptible to measles virus (OR=1.81, 95%CI: 1.33-2.47). Four age groups had
higher risk of being susceptible to measles virus (compared with >=40 years: 20
24 years old, OR=2.04, 95%CI: 1.26-3.31; 25-29 years old, OR=3.72, 95%CI: 2.37
5.86; 30-34 years old, OR=1.94, 95%CI: 1.22-3.09; 35-39 years old, OR=1.81,
95%CI: 1.07-3.05). Conclusion: Our results suggest that the serological
susceptibility in adults (20-39 years), especially adults from the regions where
the economic development was moderate, should be concerned. The additional
vaccination strategy targeting young adults is important for reducing the risk of
measles infection.
PMID- 29334707
TI - [Comparing the immunogenicity and safety of sequential inoculation of sIPV
followed by bOPV (I+III) in different dosage forms].
AB - Objective: To compare the safety and immunogenicity of two different sequential
schedules of inactivated poliomyelitis vaccine made from Sabin strain (sIPV)
followed by typeI+III bivalent oral poliovirus vaccine (bOPV) in Drug Candy (DC)
form or liquid dosage form). Methods: This randomized, blinded, single center,
parallel-group controlled trial was done from September 2015 to June 2016 in
Liuzhou, Guangxi province. Healthy infants aged >=2 months were eligible for
enrollment and divided into 1sIPV+2bOPV or 2sIPV+1bOPV sequential schedules.
According to the bOPV dosage form each sequential schedules, the subjects again
were divided into drug candy(DC) form or liquid dosage form group, being
1sIPV+bOPV (DC)/1sIPV+2bOPV(liquid)/2sIPV+1bOPV(DC)/2sIPV+1bOPV(liquid).
According to 0, 28, 56 d immunization schedule, Each group were given 3 doses. We
recorded adverse events during the clinical trial (399 participants who receive
at least one dose). 28 days post-Dose 3, we receive a total of 350 blood samples
(excluding the quitters or subjects against trial plan), using cell culture trace
against polio virus neutralization test I, II, III neutralizing antibody (GMT),
calculating the antibody positive rate.PolioI,IIand III antibody titers were
assessed by virus-neutralizing antibody assay and the seroconversion (4-fold
increase in titer) from pre-Dose 1 to 28 days post-Dose 3 was calculated (total
350 samples) . Results: During the vaccination, the incidence of AEs in
1sIPV+2bOPV(DC), 1sIPV+2bOPV (liquid), 2sIPV+1bOPV(DC), 2sIPV+1bOPV (liquid)
group were 79%, 76%, 80% and 74% (chi(2)=1.23, P=0.747) , respectively. The
severe AEs in groups were 6%, 5%, 6% and 4% (chi(2)=0.57, P=0.903) ,
respectively, and none was considered to be vaccination related. 28 days after
3(rd) vaccination, the seroconversion rates in 1sIPV+2bOPV (DC), 1sIPV+2bOPV
(liquid), 2sIPV+1bOPV (DC), 2sIPV+1bOPV (liquid) group, were 99%, 100%, 99% and
99% (chi(2)=0.94, P=0.815) , respectively, for type I poliovirus; and 47%, 57%,
80%, 79% (chi(2)=31.56, P<0.001) , respectively, for type II; and were 100%, 99%,
100%, 99% (chi(2)=2.02, P=0.568) , respectively, for type III. In each group, the
GMT of antibody against poliovirus typeI were 4 539.68, 6 243.43, 6 819.53 and 7
916.29 (F=25.87, P<0.001) , respectively; Type II were 12.98, 10.54, 63.75 and
84.21 (F=8.68, P=0.034) , respectively; Type III were 1 172.55, 1 416.03, 2
648.89 and 3 250.75 (F=14.50, P=0.002) , respectively. Conclusion: On the same
sequential schedules, there was no significant difference between the dosage
forms, all of them showed good safety and immunogenicity. In the same dosage
forms with different sequential schedules, the seroconversion rate was higher in
2 dose sIPV group than the 1 dose sIPV group, especially at the neutralizing
antibody GMT level against polio type II and III after vaccination.
PMID- 29334709
TI - [Molecular epidemiological study of human coronavirus OC43 in Shanghai from 2009
2016].
AB - Objective: To understand the epidemiological characteristics of Human coronavirus
(HCoV), the patterns of emergence and circulation, and the genotype distribution
of human coronavirus OC43 (HCoV-OC43) from November, 2009 to April, 2016 in
Shanghai. Methods: A total of 6 059 respiratory specimens, including pharyngeal
swab, sputum, nasopharyngeal aspirates and alveolar lavage fluid, as well as
relative clinical data were collected from patients with acute respiratory
infections from seven sentinel hospitals during November, 2009 to April, 2016 in
Shanghai. Respiratory specimens were tested by RT-PCR with HCoV-conserved primers
and subsequently genotyped by DNA sequencing. Using specific primers to amplify
and sequence full-length Spike (S), RNA-dependent RNA polymerase (RDRP) and
nucleocapsid (N) gene from HCoV-OC43 positive samples. Further genotype and
phylogenetic analysis of HCoV-OC43 were performed by conducting phylogenetic
trees. Results: Among 6 059 patients, the total frequency of HCoV was 63 (1.04%),
in which HCoV-OC43 was the most frequently detected species with 34 positive
samples, followed by human coronavirus 229E (HCoV-229E) and human coronavirus
HKU1 (HCoV-HKU1) with 18 and 10 positive sample respectively. However, other HCoV
like human coronavirus NL63 (HCoV-NL63), severe acute respiratory syndrome
coronavirus (SARS-CoV) and Middle-East Respiratory Syndrome Coronavirus (MERS
CoV), were not been detected, which illustrated that HCoV-OC43 was the dominant
subtype. The full-length of S, RDRP and N gene were obtained from 29 HCoV-OC43
positive samples. According to the sequence-analysis, 27 of which was genotype D,
2 of which was genotype B and others genotype, including genotype E, F and G,
were not detected. The result indicated that the genotype D may be the dominant
genotype. Further analysis of S protein that help HCoV-OC43 to entry host cell
and stimulate the host immune system to produce neutralizing antibody found that
two important functional domains in S protein, N-terminal domain (NTD) and
receptor-binding domain (RBD) contained more amino acid substitution and positive
selection sites, accompanied with amino acid insertion/deletion. 13 positive
selection sites were all located in the NTD or RBD, 10 of which were located in
the NTD and 3 in the RBD. Conclusion: Human coronavirus OC43 was the major
circulation human coronaviurs in Shanghai from 2009 to 2016, in which genotype D
was the dominant genotype. NTD and RBD regions of the S protein were
hypervariable region during HCoV-OC43 evolution, and had amino acid substitutions
as well as amino acid insertion/deletion.
PMID- 29334710
TI - [A study on genotype of 271 mycobacterium tuberculosis isolates in 6 prefectures
in Yunnan Province].
AB - Objective: To understand the characteristics of genotypes of Mycobacterium
tuberculosis isolates in Yunnan province, and provide the molecular
epidemiological evidence for prevention and control of tuberculosis in Yunnan
Province. Methods: Mycobacterium Tuberculosis isolates were collected from 6
prefectures of Yunnan province in 2014 and their Genetypes of Mycobacterium
tuberculosis isolates were obtained using spoligotyping and multiple locus
variable numbers of tandem repeats analysis (MLVA). The results of spoligotyping
were entered into the SITVITWEB database to obtain the Spoligotyping
International Type (SIT) patterns and the sublineages of MTB isolates. The
genoyping patterns were clustered with BioNumerics (version 5.0). Results: A
total of 271 MTB isolates represented patients were collected from six
prefectures in Yunnan province. Out of these patients, 196 (72.3%) were male. The
mean age of the patients was (41.9+/-15.1) years. The most MTB isolates were from
Puer, totally 94 iusolates(34.69%). Spoligotyping analysis revealed that 151
(55.72%) MTB isolates belonged to the Beijing genotype, while the other 120
(44.28%) were from non-Beijing genotype; 40 genotypes were consisted of 24 unique
genotypes and 16 clusters. The 271 isolates were differentiated into 30 clusters
(2 to 17 isolates per cluster) and 177 unique genotypes, showing a clustering
rate of 23.62%. Beijing genotype strains showed higher clustering rate than non
Beijing genotype strains (29.14% vs 16.67%). The HGI of 12-locus VNTR in total
MTB strains, Beijing genotype strains and non-Beijing genotype was 0.993, 0.982
and 0.995 respectively. Conclusion: The Beijing genotype was the predominant
genotype in Yunnan Province, the characteristics of Mycobacterium tuberculosis
showed high genetic diversity. The genotyping data reflect the potential recent
ongoing transmission in some area, which highlights the urgent need for early
diagnosis and treatment of the infectious TB cases, to cut off the transmission
and avoid a large TB outbreak.
PMID- 29334711
TI - [Serologic surveillance indicators analysis among syphilis-infected pregnant
women in East China].
AB - Objective: To analyze serologic surveillance indicators during pregnancy among
syphilis-infected women who delivered in 2013 in East China. Methods: Data were
from national 'Information System of Prevention of Mother-to-child Transmission
of HIV, syphilis and HBV Management' and in total 5 206 syphilis-infected
pregnant women who delivered in 2013 and in East China were involved in the
analysis. Information on demographic characters, laboratory tests, and treatment
regimens were collected. The maternal non-treponemal testing surveillance and
titer distribution were described and compare the proportions between pregnant
women receiving standard testing and non-standard testing, taking baseline
testing and testing before delivery or at the third trimester. Multivariate
logistic regression model was analyzed using maternal titer control as dependent
variable, using prior history of syphilis infection, syphilis stages, titer,
gestational weeks of treatment initiation and treatment regimens as independent
variables in 3 940 pregnant women with both baseline testing results and testing
results before delivery or at the third trimester. Results: The ages of the 5 206
syphilis infected pregnant women were (28.1+/-5.8) years old. The numbers of
women received penicillin treatment, other treatment regimens and no treatment
were 2 967 (57.0%), 281 (5.4%), and 1 958 (37.6%), respectively. The number of
women with maternal seroconversion, 4-fold or greater titer decline, or titer
increase were 349 (6.7%), 251 (4.8%) and 28 (0.5%). Multivariate analysis results
showed that compared with pregnant women with prior history of syphilis, the
OR(95%CI) for maternal titer control was 1.49 (1.18-1.88) among those with
syphilis-infection history. Compared with pregnant women initiated treatment at
28 gestational weeks or before, the OR (95%CI) for maternal titer control was
4.09 (3.19-5.24) among those who initiated treatment after 28 gestational weeks.
Compared with pregnant women initiated treatment at 28 gestational weeks or
before, the OR (95%CI) for maternal titer control was 4.09 (3.19-5.24) among
those who initiated treatment after 28 gestational weeks or received no
treatment. Compared with pregnant women received penicillin treatment, the OR
(95%CI) for maternal titer control among those received non-penicillin treatment
and those received no treatment were 2.35 (1.46-3.76) and 1.55 (1.13-2.12),
respectively. Conclusion: In East China, the proportion of women achieved
seroconversion or 4-fold or greater titer decline during pregnancy was very low.
Pregnant women with no prior history of syphilis infection, early maternal
initiation of treatment, and penicillin treatment were more likely to reach
maternal titer control.
PMID- 29334712
TI - [The effect of ambient PM(10) on sperm quality in Wuhan].
AB - Objective: To investigate the effect of exposure to particulate matter <=10 MUm
in aerodynamic diameter (PM(10)) on sperm quality in different stages of sperm
development. Methods: This cross-sectional study included 1 827 patients
attending the reproductive medicine center in Renmin Hospital of Wuhan University
during April 2013 to January 2015. Air pollution data from January 2013 to
January 2015 was obtained from the database of Wuhan Municipal Environmental
Protection Bureau. The generalized linear model was employed to assess the
association between each exposure variables and sperm parameters for several
exposure windows (0-9, 10-14, 15-69, 70-90, 0-90 days before sampling) . Results:
The average levels of PM(10) was (116.2+/-71.6) MUg/m(3) during the research
period. Sperm volume was (75.4+/-49.1) *10(6)/ml in sample population, (29.4+/
16.2) % in progressive motility and (51.8+/-21.6) % in total motility. Exposure
to PM(10) was inversely associated with sperm concentration (beta:-0.319; 95%CI:
0.529,-0.046) during 70-90 lag days. PM(10) exposure during the 0-90 lag days was
significantly associated with progressive motility (beta:-0.312; 95%CI:-0.527,
0.097) and total motility (beta:-0.347; 95%CI:-0.636,-0.059) after adjusted for
age, education level, BMI, smoking, abstinence time, temperature, humidity and
season. Conclusion: Exposure to PM(10) was associated with statistically
significant decrements in sperm concentration and motility, and the adverse
impact on sperm concentration was significantly in early phases of
spermatogenesis.
PMID- 29334713
TI - [Prevalence and influential factors of stroke in Jiangxi Province in 2014].
AB - Objective: To discuss the prevalence and influential factors of stroke among
population in Jiangxi Province. Methods: Four cities in urban areas and four
counties in rural areas were selected firstly, in which two districts or
townships were selected; and then three communities or villages were chosen from
each district and township, respectively, using the simple random sampling (SRS)
method. Finally 15 269 subjects aging 15 years old or above, living in Jiangxi
Province >=6 months were randomly selected to participate in this survey from
November 2013 to August 2014. Information of population characteristics, life
behavior way, individual disease history were collected through questionnaire
survey, and height, weight, waist circumference, blood pressure, body fat rate,
visceral fat index and so on were measured by instruments. Risk factors of stroke
prevalence were analyzed by the unconditioned logistic regression analysis.
Results: A total of 15 269 participants (6 267 males) from 15 364 eligible
participants were included in the statistical analysis. Out of which, 7 793
participants came from urban areas, and their average age was (53.04+/-17.91)
years old. In this study, 226 stroke patients (117 males) were found among15 269
participants, including 122 urban participants and 104 rural participants, whose
average age was (67.76+/-9.74) years old. The prevalence of stroke was 1
480.12/100 000 in 2014, which was separately 1 866.92/100 000 and 1 210.84/100
000 among males and females. The prevalence of people aging (45-49) years old was
413.79/100 000 (6/1 450) , while which among people aging 75 years old and above
was 3 311.62/100 000 (61/1 842) . The prevalence of stroke among residents in
Jiangxi presented an uprising tendency with age increasing (linear-by-linear
association chi(2)=62.23, P<0.01). The research showed that when other
influencing factors including gender, BMI, waist circumference, pulse-pressure
difference, VAI, and sleeping time in non-working days were controlled,
hypertensive patients had a higher risk of stroke than people without
hypertension (OR=6.88, 95%CI: 4.90-9.67), drinkers had a higher risk of stroke
than non-drinkers (OR=1.56, 95%CI: 1.17-2.08), compared with people <65 years
old, people aged 65-74 years old and >=75 years old had a higher risk of stroke,
the value of OR (95%CI) were 1.88 (1.36-2.59) and 1.97 (1.39-2.80), respectively,
compared with people with normal body fat percentage, people whose body fat
percentage on high side and people who with high body fat percentage had a higher
risk of stroke, the value of OR (95%CI) were 1.71 (1.18-2.48) and 1.74 (1.18
2.56), respectively, people with sleep time >8 h had a higher risk of stroke than
those with sleep time of 6-8 h. Conclusion: There was a high stroke prevalence
among residents in Jiangxi province. Hypertension, drinking, age, BFP and sleep
duration were associated with stroke prevalence. Corresponding measures for high
risk population and risk factors should be strengthened to prevent and control
the stroke.
PMID- 29334714
TI - [Urinary iodine concentration status and its influencing factors of pregnant
women in Yuhuan county, Zhejiang Province].
PMID- 29334715
TI - [Analysis of HCV infection rate and its influence factors among drug users in
Dehong Prefecture, Yunnan Province].
PMID- 29334716
TI - [Analysis on surveillance data of immunization safety for varicella vaccine after
the immunization strategy implemented].
PMID- 29334717
TI - [The ten-year retrospect of nutrition and health status of pregnant women in
China].
AB - Improvement of the nutrition and health status of pregnant women should be one of
the top priority strategies of improving the physical fitness of next generation
and reserve of talented person for national sustainable development. This paper
reviews the nutrition and health status of pregnant women in China over the
recent ten years and discusses the underlying factors and changing trends. The
most popular nutrition-related problem is dietary imbalance, and many
micronutrient intakes are lower than the recommended dietary intakes or adequate
intakes, and some of nutrient intakes are still at a very low level for a long
time such as vitamin D and calcium. The nutrition-related health problems are
mainly anemia, vitamin D and vitamin A deficiencies; iodine intake is not in
optimal state with a large proportion of inadequate and individual cases facing
excessive intake risk. Overweight and obesity, pregnancy complications such as
gastrocnemius muscle spasms, pregnancy hypertensive disorders and gestational
diabetes were prevalent among pregnant women. We should address both malnutrition
and nutrition imbalance in the same time in order to improve the nutrition and
health status of pregnant women, by developing and implementing relevant laws and
regulations, giving higher attention to pregnant women with advanced age, which
in turns prevent a variety of micronutrient deficiencies, reduce adverse pregnant
outcomes, and improve nutrition and health status of maternal and child.
PMID- 29334718
TI - [Diet and nutrition interventions prevent gestational diabetes mellitus].
AB - Gestational diabetes mellitus (GDM) is one of the most common complications
during pregnancy, with rising trend over the years. Dietary nutrient intake
(protein, fat and fatty acids, carbohydrate, vitamin D, vitamin E, iron, zinc,
selenium and inositol et al.), dietary pattern and probiotics may be related to
GDM occurrence. Dietary factors are modifiable factors for preventing GDM. The
study reviewed the roles of these dietary factors in preventing GDM. Results
showed that plant-based dietary pattern may lower the risk of GDM and dietary
pattern characterized with high animal protein, high fat and low carbohydrate may
increase the risk of GDM. It warrants further studies that nutrient
supplementation may prevent pregnant women from GDM. Diverse diet based on plant
and cereal food should be promote for healthy and appropriate weight gain during
pregnancy.
PMID- 29334719
TI - [Human papillomavirus infection and vaccination].
AB - Human papillomavirus (HPV) is an infection that can be sexually transmitted and
result in health consequences. Persistent high-risk HPV infection can lead to
various cancers and is the essential cause of cervical cancer. HPV vaccine can
prevent the HPV infection and thus the incidence of cervical cancer. In this
review we introduced the prevalence of HPV infection and vaccination, and the
prevention and early detection of cervical cancer. We also introduced the present
knowledge and awareness of HPV infection and HPV vaccine in Chinese. Propaganda
all over China should be performed on HPV vaccination to improve the vaccination
rate, thus preventing the incidence of cervical cancer.
PMID- 29334720
TI - [Responding to national strategy demand for a new era, and grasping key problems
of basic frontiers in preventive medicine--Shuangqing Forum (No. 192) of National
Natural Science Foundation of China].
PMID- 29334721
TI - Efficacy and safety of tocilizumab in Korean patients with active rheumatoid
arthritis.
AB - Background/Aims: To investigate the efficacy and safety of tocilizumab (TCZ)
humanized anti-interleukin-6 receptor monoclonal antibody, in Korean patients
with active rheumatoid arthritis (RA) refractory to conventional disease
modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX). Methods:
The main study was a 24-week, randomized, double-blind, controlled trial that was
followed by a 48-week, open-labeled, extension phase. TCZ (8 mg/kg) or placebo
was intravenously administered every 4 weeks. Results: Those treated with TCZ
showed more favorable outcomes in terms of 20% according to the American College
of Rheumatology response criteria (ACR20) and ACR50 responses, individual
parameters of ACR core set, disease activity score in 28 joints (DAS28)
remission, and European League Against Rheumatism (EULAR) response at week 24.
These improvements were maintained or increased during the extension period.
DAS28 remission at week 72 was associated with EULAR good response at week 12.
The patients who experienced any adverse event (AE) were more frequent in the TCZ
group compared to the placebo group. Most AEs were mild or moderate in intensity,
although TCZ therapy had possible AEs including serious infection, abnormal liver
function, and atherogenic lipid profile. Conclusions: TCZ infusion add-on is
highly efficacious and well-tolerated in Korean patients with active RA
refractory to conventional DMARDs including MTX. EULAR good response at week 12
could predict DAS28 remission at week 72.
PMID- 29334722
TI - Comparison of the morphologic criteria (RECIST) and metabolic criteria (EORTC and
PERCIST) in tumor response assessments: a pooled analysis.
AB - Background/Aims: The Positron Emission Tomography Response Criteria in Solid
Tumors (PERCIST) or European Organization for Research and Treatment of Cancer
(EORTC) criteria are used to assess metabolic tumor responses. However, tumor
responses have shown considerable discrepancies between the morphologic criteria
(Response Evaluation Criteria in Solid Tumors [RECIST]) and metabolic criteria.
We performed this pooled study to compare the RECIST and metabolic criteria in
the assessment of tumor responses. Methods: Electronic databases were searched
for eligible articles with the terms "RECIST," "PERCIST," or "EORTC criteria."
The level of concordance in the tumor responses between the two criteria was
estimated using kappa statistics. Results: A total of 216 patients were collected
from eight studies comparing the RECIST and EORTC criteria. The agreement of
tumor responses between the two criteria was moderate (kappa = 0.447). Eighty-six
patients (39.8%) showed disagreement: tumor response was upgraded in 70 patients
and downgraded in 16 when adopting the EORTC criteria. The EORTC criteria
significantly increased the overall response rate (53% vs. 28%, p < 0.0001). The
agreement of tumor responses between the RECIST and PERCIST was deemed fair
(kappa = 0.389). Of 407 patients from nine studies, 181 (44.5%) showed a
discrepancy: using the PERCIST, tumor response were upgraded in 151 patients and
downgraded in 30. When adopting the PERCIST, the overall response rate was also
significantly increased from 30% to 55% (p < 0.0001). Conclusions: This pooled
analysis demonstrates that the concordance of tumor responses between the
morphologic criteria and metabolic criteria is not excellent. When adopting the
metabolic criteria instead of the RECIST, overall response rates were
significantly increased.
PMID- 29334723
TI - Methacholine bronchial provocation test in patients with asthma: serial
measurements and clinical significance.
AB - Background/Aims: The methacholine bronchial provocation test (MBPT) is used to
detect and quantify airway hyper-responsiveness (AHR). Since improvements in the
severity of asthma are associated with improvements in AHR, clinical studies of
asthma therapies routinely use the change of airway responsiveness as an
objective outcome. The aim of this study was to assess the relationship between
serial MBPT and clinical profiles in patients with asthma. METHODS: A total of
323 asthma patients were included in this study. The MBPT was performed on all
patients beginning at their initial diagnosis until asthma was considered
controlled based on the Global Initiative for Asthma guidelines. A responder was
defined by a decrease in AHR while all other patients were considered non
responders. RESULTS: A total of 213 patients (66%) were responders, while 110
patients (34%) were non-responders. The responder group had a lower initial PC20
(provocative concentration of methacholine required to decrease the forced
expiratory volume in 1 second by 20%) and longer duration compared to the non
responder group. Members of the responder group also had superior qualities of
life, compared to members of the non-responder group. Whole blood cell counts
were not related to differences in PC20; however, eosinophil concentration was.
No differences in sex, age, body mass index, smoking history, serum
immunoglobulin E, or frequency of acute exacerbation were observed between
responders and non-responders. Conclusions: The initial PC20, the duration of
asthma, eosinophil concentrations, and quality-of-life may be useful variables to
identify improvements in AHR in asthma patients.
PMID- 29334724
TI - Disparity in Crohn's disease activity between home and clinics is associated with
unscheduled hospital visits due to disease flares.
AB - BACKGROUND/AIMS: E-health technologies have been implemented for the management
of Crohn's disease (CD). We aimed to identify differences between patient
activities at home and at routine clinic visits using a web-based self-reporting
CD symptom diary (CDSD) and to determine the impact of this disparity on clinical
outcomes. METHODS: Patients with CD from three tertiary hospitals were invited to
assess their symptoms at least once a week using CDSD. We identified patients who
showed disparities in disease activity (high activity at home but normal at the
next hospital visit) and evaluated clinical outcomes of these patients such as
unscheduled visits due to flares using Kaplan-Meier analyses. RESULTS: One
hundred and forty-three patients recorded their symptoms weekly for at least 3
consecutive months and were included. Forty-eight patients (33.6%) showed
disparate disease activities between at home and at the next outpatient clinic
visit. The cumulative risk of unscheduled visits was significantly higher in this
disparity group than in the concordant group (p = 0.001). Disparity in activity
(p = 0.003), and anti-tumor necrosis factor use (p = 0.002) were independent risk
factors of unscheduled visits due to disease flares. CONCLUSION: Disparity in
disease activity is considerable in CD patients and is related to the risk of
unscheduled hospital visit.
PMID- 29334725
TI - Physical activity in chronic obstructive pulmonary disease: clinical impact and
risk factors.
PMID- 29334726
TI - Procalcitonin in bloodstream infections: beyond its role as a marker of clinical
algorithm to reduce antimicrobial overuse.
PMID- 29334727
TI - ApoB/ApoA-I ratio is independently associated with carotid atherosclerosis in
type 2 diabetes mellitus with well-controlled LDL cholesterol levels.
AB - BACKGROUND/AIMS: This study aimed to investigate whether the apolipoprotein (Apo)
B/ApoA-I ratio is associated with carotid intima-media thickness (CIMT) in type 2
diabetes mellitus (T2DM) subjects with low density lipoprotein cholesterol (LDL
C) levels less than 100 mg/dL. METHODS: This cross-sectional study included 845
subjects aged with T2DM 40 to 75 years who had visited Huh's Diabetes Center in
Seoul, Republic of Korea for CIMT measurement. Traditional fasting lipid
profiles, ApoB and ApoA-I levels were examined. CIMT was measured at three points
on the far wall of 1 cm long section of the common carotid artery in the
proximity of the carotid bulb. The mean value of six measurements from right and
left carotid arteries were used as the mean CIMT. In this study, carotid
atherosclerosis was defined as having a focal plaque or diffuse thickening of the
carotid wall (mean CIMT >= 1.0 mm). RESULTS: The prevalence of carotid
atherosclerosis increased with ApoB/ApoA-I ratio. The ApoB/ApoA-I ratio,
expressed as both quartiles (odds ratio [OR], 2.14; 95% confidence interval [CI],
1.21 to 3.79; p for trend = 0.014) and continuous values (OR, 10.05; 95% CI, 3.26
to 30.97; p < 0.001), was significantly associated with a higher risk for carotid
atherosclerosis, regardless of conventional cardiovascular disease risk factors.
The optimal ApoB/ApoA-I ratio cutoff value for detecting carotid atherosclerosis
was 0.57, based on receiver operating characteristic curve analysis with a
sensitivity of 58.0% and a specificity of 55.1%. CONCLUSIONS: A high ApoB/ApoA-I
ratio was significantly associated with carotid atherosclerosis in T2DM patients
with LDL-C levels less than 100 mg/dL.
PMID- 29334728
TI - Changing treatment paradigms for the management of inflammatory bowel disease.
AB - Inflammatory bowel disease (IBD) is a chronic and progressive inf lammatory
condition of the gastrointestinal tract causing bowel damage, hospitalizations,
surgeries, and disability. Although there has been much progress in the
management of IBD with established and evolving therapies, most current
approaches have failed to change the natural course. Therefore, the treatment
approach and follow-up of patients with IBD have undergone a significant change.
Usage of immunosuppressants and/or biologics early during the course of the
disease, known as top-down or accelerated step-up approach, was shown to be
superior to conventional management in patients who had been recently diagnosed
with IBD. This approach can be applied to selected groups based on prognostic
factors to control disease activity and prevent progressive disease. Therapeutic
targets have been shifted from clinical remission mainly based on symptoms to
objective parameters such as endoscopic healing due to the discrepancies observed
between symptoms, objectively evaluated inf lammatory activity, and intestinal
damage. The concept of treat-to-target in IBD has been supported by population
based cohort studies, post hoc analysis of clinical trials, and meta-analysis,
but more evidence is needed to support this concept to be applied to the clinical
practice. In addition, individualized approach with tight monitoring of non
invasive biomarker such as C-reactive protein and fecal calprotectin and drug
concentration has shown to improve clinical and endoscopic outcomes. An
appropriate de-escalation strategy is considered based on patient demographics,
disease features, current disease status, and patients' preferences.
PMID- 29334729
TI - Polyoxygenated Cyclohexenoids with Promising alpha-Glycosidase Inhibitory
Activity Produced by Phomopsis sp. YE3250, an Endophytic Fungus Derived from
Paeonia delavayi.
AB - Seven new polyoxygenated cyclohexenoids, namely, phomopoxides A-G (1-7), were
isolated from the fermentation broth extract of an endophytic fungal strain
Phomopsis sp. YE3250 from the medicinal plant Paeonia delavayi Franch. The
structures of these compounds were established by spectroscopic interpretation.
The absolute configurations of compounds 1 and 4 were confirmed by X-ray
crystallographic analysis and chemical derivative approach. All isolated
compounds showed weak cytotoxic activities toward three human tumor cell lines
(Hela, MCF-7, and NCI-H460) and weak antifungal activities against five
pathogenic fungi (Candida albicans, Aspergillus niger, Pyricularia oryzae,
Fusarium avenaceum, and Hormodendrum compactum). In addition, compounds 1-7
showed a promising alpha-glycosidase inhibitory activity with IC50 values of
1.47, 1.55, 1.83, 2.76, 2.88, 3.16, and 2.94 mM, respectively, as compared with a
positive control of acarbose (IC50 = 1.22 mM).
PMID- 29334730
TI - Decomposition Pathways of Titanium Isopropoxide Ti(OiPr)4: New Insights from UV
Photodissociation Experiments and Quantum Chemical Calculations.
AB - The UV-photodissociation at 266 nm of a widely used TiO2 precursor, titanium
tetraisopropoxide (Ti(OiPr)4, TTIP), was studied under molecular-beam conditions.
Using the MS-TOF technique, atomic titanium and titanium(II) oxide (TiO) were
detected among the most abundant photofragments. Experimental results were
rationalized with the aid of quantum chemical calculations (DLPNO-CCSD(T) and
DFT). Contrary to the existing data in the literature, the new four-centered
acetone-elimination reaction was found to be the primary decomposition process of
TTIP. According to computational results, the effective activation barrier of
this channel was ~49 kcal/mol, which was ~13 kcal/mol lower than that of the
competing propylene elimination. The former process, followed by the dissociative
loss of an H atom, was a dominating channel of TTIP unimolecular decay. The
sequential loss of isopropoxy moieties via these two-step processes was supposed
to produce the experimentally observed titanium atoms. In turn, the combination
of these reactions with propylene elimination can lead to another detected
species, TiO. These results indicate that the existing mechanisms of TTIP thermal
and photoinitiated decomposition in the chemical-vapor deposition (CVD) of
titanium dioxide should be reconsidered.
PMID- 29334731
TI - Validity of Measuring Metallic and Semiconducting Single-Walled Carbon Nanotube
Fractions by Quantitative Raman Spectroscopy.
AB - Although it is known that the Raman spectroscopic signature of single-walled
carbon nanotubes (SWCNTs) is highly chirality dependent, using Raman spectroscopy
with several laser excitations as a tool for quantifying fraction of either
metallic or semiconducting nanotubes in a sample has become a widely used
analytical method. In this work, using the electron diffraction technique as a
basis, we have examined the validity of Raman spectroscopy for quantitative
evaluation of metallic fractions (M%) in single-walled carbon nanotube samples.
Our results show that quantitative Raman spectroscopic evaluations of M% by using
several discrete laser lines, either by using integrated intensities of chirality
associated radial breathing modes (RBMs) or, as has been more commonly utilized
in recent studies, by statistically counting the numbers of RBMs can be
misrepresentative. Specifically, we have found that the occurrence numbers of
certain types of RBMs in Raman spectral mapping depend critically on the diameter
distribution, resonant coupling between transition energies and excitation laser
energy, and the chirality-dependent Raman scattering cross sections rather than
simply on the metallic and semiconducting SWCNT fractions. These dependencies are
similar to those observed in the integrated intensities of RBMs. Our findings
substantially advance the understanding of the proper use of Raman spectroscopy
for carbon nanotube quantification, which is important for carbon nanotube
characterization and crucial to guide research in SWCNT growth and their
applications.
PMID- 29334732
TI - Fine Art of Thermoelectricity.
AB - A detailed study of hitherto unknown electrical and thermoelectric properties of
graphite pencil traces on paper was carried out by measuring the Hall and Seebeck
effects. We show that the combination of pencil-drawn graphite and brush-painted
poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) films on
regular office paper results in extremely simple, low-cost, and environmentally
friendly thermoelectric power generators with promising output characteristics at
low-temperature gradients. The working characteristics can be improved even
further by incorporating n-type InSe flakes. The combination of pencil-drawn n
InSe:graphite nanocomposites and brush-painted PEDOT:PSS increases the power
output by 1 order of magnitude.
PMID- 29334733
TI - Surface Functionalization with Carboxylic Acids by Photochemical Microcontact
Printing and Tetrazole Chemistry.
AB - In this paper, we show that carboxylic acid-functionalized molecules can be
patterned by photochemical microcontact printing on tetrazole-terminated self
assembled monolayers. Upon irradiation, tetrazoles eliminate nitrogen to form
highly reactive nitrile imines, which can be ligated with several different
nucleophiles, carboxylic acids being the most reactive. As a proof of concept, we
immobilized trifluoroacetic acid to monitor the reaction with X-ray photoelectron
spectroscopy. Moreover, we also immobilized peptides and fabricated carbohydrate
lectin as well as biotin-streptavidin microarrays using this method. Surface
patterning was demonstrated by fluorescence microscopy and time-of-flight
secondary ion mass spectrometry.
PMID- 29334735
TI - Complex Dynamics of Photo-Switchable Guest Molecules in All-Optical Poling Close
to the Glass Transition: Kinetic Monte Carlo Modeling.
AB - We study theoretically the kinetics of noninteracting photoswitchable guest
molecules (model azo-dye) dispersed at low concentration in host (model polymer
matrix) in the all-optical poling process close to the glass transition
temperature Tg. We modify kinetic Monte Carlo model used in our previous studies
of nonlinear optical processes in host-guest systems. The polymer matrix is
simulated using the bond-fluctuation model. The kinetics of multiple trans-cis
trans cycles is formulated in terms of transition probabilities which depend on
local free volume in the matrix and its dynamics. Close to Tg, the buildup of
polar order, monitored in terms of angular probability density functions, follows
a power-law in time while the evolution of the nonlinear susceptibilities related
to second harmonic generation effect follows the stretched-exponential law. This
complex dynamics of guest molecules implies the presence of dynamic
heterogeneities of the matrix in space and time which spread the complexity from
the matrix to the otherwise simple dynamics of noninteracting guest molecules. A
qualitative physical picture of mosaic-like states-intertwined areas of free- and
hindered angular motion of guest molecules-is proposed and the role of related
short and longer scales in space for the promotion of complex dynamics of guest
molecules is discussed. A brief comparison of the theory to available
experimental data is given.
PMID- 29334734
TI - A Method for Selective Depletion of Zn(II) Ions from Complex Biological Media and
Evaluation of Cellular Consequences of Zn(II) Deficiency.
AB - We describe the preparation, evaluation, and application of an S100A12 protein
conjugated solid support, hereafter the "A12-resin", that can remove 99% of
Zn(II) from complex biological solutions without significantly perturbing the
concentrations of other metal ions. The A12-resin can be applied to selectively
deplete Zn(II) from diverse tissue culture media and from other biological
fluids, including human serum. To further demonstrate the utility of this
approach, we investigated metabolic, transcriptomic, and metallomic responses of
HEK293 cells cultured in medium depleted of Zn(II) using S100A12. The resulting
data provide insight into how cells respond to acute Zn(II) deficiency. We expect
that the A12-resin will facilitate interrogation of disrupted Zn(II) homeostasis
in biological settings, uncovering novel roles for Zn(II) in biology.
PMID- 29334736
TI - Hydration Behavior along the Folding Pathways of Trpzip4, Trpzip5 and Trpzip6.
AB - The microscopic properties of water confined within different segments of Trpzip4
(TZ4), Trpzip5 (TZ5), and Trzpip6 (TZ6) have been compared for all the states
characterized along their folding pathways. In particular, structural ordering,
energetics, and dynamics of water have been examined as the peptide unfolds along
the free energy landscape. It is observed that the structuring of tetrahedral
network as well as translational and rotational motions of hydration waters
confined within the strands and the turn regions are very different, revealing
motional heterogeneity in small 16-residue trpzips. The polar and charged groups
present at the peptide surface anchor to water molecules through hydrogen bonds
and are responsible for differential hydration among various segments of the
peptide, which is found to be correlated to their hydropathy values. The coherent
collective dynamics of water is strongly coupled with conformational changes in
the peptide since the trends observed in most of the computed quantities are in
accordance with the folded and unfolded states classified along the folding
pathway for all trpzips. The hydration behavior conform to the heterogeneity
observed in the free energy landscape of stable TZ4 with four unfolded states as
compared to more flexible TZ5 and TZ6 with two unfolded states each, in addition
to the folded state. The hydration waters are observed to regulate the protein
dynamics by continuous fluctuations in hydrogen bond network involving lateral
side chains that inject conformational motions in the peptide to facilitate its
unfolding. The implications of mutations on various aspects of hydration water
dynamics including their impact on structural and dynamic organization of
hydrogen bonds are also highlighted. Our studies affirm that topology of the free
energy landscape is shaped by both spatial organization and dynamic transitions
in hydration waters in addition to the conformational fluctuations in the peptide
along the folding pathway.
PMID- 29334737
TI - Tubular Hybrids: A Nanoparticle-Molecular Network.
AB - We report here a new methodology for the formation of freestanding nanotubes
composed of individual gold nanoparticles (NPs) cross-linked by coordination
complexes or porphyrin molecules using WS2 nanotubes (INT-WS2) as a template. Our
method consists of three steps: (i) coverage of these robust inorganic materials
with monodispersed and dense monolayers of gold NPs, (ii) formation of a
molecular AuNP network by exposing these decorated tubes to solutions containing
a ruthenium polypyridyl complex or meso-tetra(4-pyridyl)porphyrin, and (iii)
removal of the INT-WS2 template with a hydrogen peroxide solution.
Nanoindentation of the template-free AuNP tubes with atomic force microscopy
indicates a radial elastic modulus of 4 GPa. The template-free molecular AuNP
tubes are characterized using scanning and transmission electron microscopy,
energy-dispersive X-ray spectroscopy, and micro-Raman spectroscopy. The
methodology provides a convenient and scalable strategy for the realization of
molecular AuNP tubes with a defined length and diameter, depending on the
dimensions of the template.
PMID- 29334738
TI - Quantitative Visualization of Salt Concentration Distributions in Lithium-Ion
Battery Electrolytes during Battery Operation Using X-ray Phase Imaging.
AB - A fundamental understanding of concentrations of salts in lithium-ion battery
electrolytes during battery operation is important for optimal operation and
design of lithium-ion batteries. However, there are few techniques that can be
used to quantitatively characterize salt concentration distributions in the
electrolytes during battery operation. In this paper, we demonstrate that in
operando X-ray phase imaging can quantitatively visualize the salt concentration
distributions that arise in electrolytes during battery operation. From
quantitative evaluation of the concentration distributions at steady states, we
obtained the salt diffusivities in electrolytes with different initial salt
concentrations. Because of no restriction on samples and high temporal and
spatial resolutions, X-ray phase imaging will be a versatile technique for
evaluating electrolytes, both aqueous and nonaqueous, of many electrochemical
systems.
PMID- 29334739
TI - Microfluidic-Assisted Production of Size-Controlled Superparamagnetic Iron Oxide
Nanoparticles-Loaded Poly(methyl methacrylate) Nanohybrids.
AB - In this paper, superparamagnetic iron oxide nanoparticles (SPIONs, around 6 nm)
encapsulated in poly(methyl methacrylate) nanoparticles (PMMA NPs) with
controlled sizes ranging from 100 to 200 nm have been successfully produced. The
hybrid polymeric NPs were prepared following two different methods: (1)
nanoprecipitation and (2) nanoemulsification-evaporation. These two methods were
implemented in two different microprocesses based on the use of an impact jet
micromixer and an elongational-flow microemulsifier. SPIONs-loaded PMMA NPs
synthesized by the two methods presented completely different physicochemical
properties. The polymeric NPs prepared with the micromixer-assisted
nanoprecipitation method showed a heterogeneous dispersion of SPIONs inside the
polymer matrix, an encapsulation efficiency close to 100 wt %, and an irregular
shape. In contrast, the polymeric NPs prepared with the microfluidic-assisted
nanoemulsification-evaporation method showed a homogeneous dispersion, an almost
complete encapsulation, and a spherical shape. The properties of the polymeric
NPs have been characterized by dynamic light scattering, thermogravimetric
analysis, and transmission electron microscope. In vitro cytotoxicity assays were
also performed on the nanohybrids and pure PMMA NPs.
PMID- 29334740
TI - Point of Departure.
PMID- 29334741
TI - Accounts: 50 Years of a Great Idea.
PMID- 29334742
TI - [Diagnostic and prognostic biomarkers in acute coronary syndrome].
AB - Acute myocardial infarction (AMI) is an important cause of mortality and
morbidity worldwide. Early diagnostics of this disease helps in the appropriate
treatment of patients. Great attention is paid to the diagnostic and risk
stratification of patients according to circulating biomarkers. There are a lot
of scientific publications describing this topic. The aim of this article is to
provide a comprehensive overview of the most important and most examined
biomarkers in acute coronary syndrome. Meanwhile troponin takes a fundamental
place for AMI diagnostic (mostly the high-sensitive methods) in preference to MB
fraction of creatine kinase and myoglobin. The connection to a higher sudden
death risk, reinfarcts and heart failure occurring was also proved by many other
biomarkers. The most important of them are the natriuretic peptides, the C
reactive protein, the heart fatty acid binding protein, the pregnancy-associated
plasma protein-A, CD146, cystatin C, NGAL, copeptin, MR-proadrenomedullin, and
the growth differentiation factor-15. More prospective randomized studies are
needed for the further use of these other biomarkers in clinical practice.Key
words: acute coronary syndrome - biomarkers.
PMID- 29334744
TI - [Selenium treatment in thyreopathies].
AB - Selenium (latin Selenium) is a micronutrient embedded in several proteins. In
adults, the thyroid is the organ with the highest amount of selenium per gram of
tissue. Selenium levels in the body depend on the characteristics of the
population and its diet and geographic area. In the thyroid, selenium is required
for the antioxidant function and for the metabolism of thyroid hormones. The
literature suggests that selenium supplementation of patients with Hashimotos
thyroiditis is associated with a reduction in antithyroperoxidase antibody
levels. Selenium supplementation also in mild Graves orbitopathy is associated
with delayed progression of ocular disorders. As a consequence of this
observation The European Group on Graves Orbitopathy recommend six months
selenium preparates supportive therapy for patients with mild form of Graves
orbitopathy.Key words: Graves-Basedows disease - Hashimotos thyroiditis -
selenium - supplementation.
PMID- 29334743
TI - [Adiponectin in patients with metabolic syndrome and diseases of the liver, bile
ducts and pancreas].
AB - Epidemiological data show that the metabolic syndrome can be diagnosed in up to
30 % of the population. Regarding 5 components of the metabolic syndrome, three
of them, in case of positivity (visceral obesity, arterial hypertension,
hypertriglyceridemia, changes of HDL-cholesterol levels and type 2 diabetes
mellitus), are pathogenic factors which are the most frequently related to
cardiovascular diseases, but currently they are also the focus of interest for
gastroenterologists. The relationship between non-alcoholic hepatic steatosis,
including non-alcoholic steatohepatitis, has been described. Less is known so far
about the relation to the pancreas disease, particularly with respect to the
status referred to as non-alcoholic fatty pancreas disease. The hormone
selectively produced by adipose tissue is adiponectin. This protein is studied as
a possible biomarker in people with metabolic syndrome, including obesity.
Besides that, there is a question studied whether adiponectin can also play a
significant role in the pathogenesis of diseases associated with fat building up
in parenchymatous organs. Finding a reliable biomarker for patients with
metabolic syndrome or diseases of the liver, biliary system and pancreas in
relation to metabolic syndrome, presents a big challenge. And adiponectin is one
of the promising biomarkers.Key words: adiponectin - biliary disease - metabolic
syndrome - pancreatic steatosis - steatohepatitis.
PMID- 29334745
TI - [Citalopram and QT prolongation].
AB - In 2011/2012, the US Food and Drug Administration issued a warning about the
effect of citalopram on the QT interval and decreased its dosing. Further studies
addressing this issue have been published since then. The authors were interested
to know whether or not the studies have furnished new information that could
modify or further specify the FDA-issued recommendations. After analyzing the
most relevant studies, the authors concluded that even papers published within
the last 5 years confirmed that, of the SSRI class of drugs, citalopram prolongs
the QT interval most significantly. While the QT interval prolongation in young
and otherwise healthy individuals is small and treatment with citalopram
relatively safe, in elderly comorbid patients with polypharmacy, use of even
currently recommended doses may result in significant QT interval prolongation.
Hence, the decision about future therapy will depend on the degree of risk of
each individual patient. Judging by the most recent data, citalopram is not more
effective compared with the other SSRIs. As a result, therapy with citalopram
will presumably show a declining trend, particularly in elderly patients.Key
words: citalopram - escitalopram - QT interval - SSRI.
PMID- 29334746
TI - [The current role of warfarin].
AB - Well-managed warfarin therapy remains an important method of anticoagulation in
the 21st century, despite the introduction of new antithrombotics into the
clinical practice. The main advantages of warfarin are decades of treatment
experience, the possibility to monitor its anticoagulant effect using the INR and
the last, but not least, the low cost. Currently, approximately 75 % of
anticoagulated patients in the Czech Republic are treated with warfarin and
warfarin remains the only option for oral anticoagulant therapy in certain
clinical conditions (particularly in patients with valvular atrial fibrillation
or mechanical heart valves). For physicians across specialties it is still
indispensable to master the basics of safe and effective warfarin therapy,
including the management of treatment complications.Key words: anticoagulant
therapy - INR - thrombosis - warfarin.
PMID- 29334747
TI - [Drug induced tendon injury].
AB - Tendon injury belongs to the less known side effects of some drugs, reported
until recently only for glucocorticoids and fluoroquinolones. To date, some other
classes of drugs such as statins, aromatase inhibitors, anabolic steroids,
potentially causing tendon injury, have been added to the list. The authors
discuss the most common clinical presentations, diagnosis, and management as well
as latest experimental data regarding this issue. The most often, the Achilles
tendon is affected, however, nearly every tendon of the entire body may be
affected. Tendon rupture or drug induced tendinopathy should be strongly
considered in those who have a tendon injury and have recently taken these
drugs.Key words: anabolic steroids - aromatase inhibitors - fluoroquinolones -
glucocorticoids - statins - tendon injury.
PMID- 29334748
TI - [How to apply the ambulatory cardiovascular rehabilitation: guidelines of the
Working group for cardiovascular rehabilitation at Slovak Society of Cardiology].
AB - Authors have proposed a concept of guidelines for applying the ambulatory complex
cardiovascular rehabilitation (ACCVR) into the clinical practice in Slovakia. As
a background they have used an actual cardiovascular mortality and morbidity data
from home country and abroad as well. They emphasize the non-optimal situation in
this aspect which may not be solved by the increasing supporting the invasive
revascularization methods and by the intensifying pharmacotherapy only, because
the favourable effects of these procedures is timely missing if it is not
accompanied by the therapeutic lifestyle changes. In this proposal the ACCVR is
considered not as a regular, controlled physical training only, but there is
included patient's education, relaxation, stress management, behavioral changes
and possible social support too. At the end of one 3 months lasting cycle of
ACCVR there is subsumed a final test oriented on patient's education and physical
fitness levels and the continuing long-term contacts with him during following
home-based training. Main parts of the concept are the concrete conditions which
should by fulfilled as for as a personal, space and device equipment needed for
accreditation so called cardiology stationary for ACCVR activities (in connection
with cardiology department for out patients). Moreover, there are also included
practical guidelines how to do patient's stratification, how to send the patients
to stationary, indications and contraindications, establishing of the training
heart rate and training load, the composition of one cycle 3 months lasting,
application of the progressive aerobic and resistance training and how to
continue in home-based training. At the end the authors have proposed conditions
which are needed to fulfil for a successful implementation of ACCVR into the
health care system.Key words: cardiovascular rehabilitation for out patients -
exercise training - home based training with telemonitoring control - progressive
resistance training - relaxation and stress management.
PMID- 29334749
TI - [Unusual history of Wilson disease: a case report and review of the literature].
AB - Wilson disease (WD) belongs to autosomal recessive genetic metabolic disorders
with gene mutation ATP7B located on 13th chromosome. The enzyme ATPase plays an
important role in WD. It facilitates excretion of copper into bile. This gene is
responsible for modification of apoceruloplasmin. In this disease, it leads to
insufficient release of copper from organism and accumulation of copper in organs
such as liver, brain which can cause dysfunction of a certain organ. According to
specific symptoms, we can divide WD into psychiatric, neurologic or hepatic form.
The WD usually manifests between 15 and 25 years of age. Hepatic form often
occurs sooner, on the contrary, the neurological variant usually occur during the
later stages. We present a case report of 45-years-old woman with atypical
medical history of WD, in which the diagnostic process was very long and had
interdisciplinary character.Key words: brain - copper - diagnostic - genetics -
liver - panda - Wilson disease.
PMID- 29334750
TI - [Remission of steroid-resistant Stills disease treated with anakinra, evidenced
by FDG-PET/CT examination: case report].
AB - After elimination of infectious causes, neoplastic causes and the systemic
autoimmune disease of connective tissue, a patient with high fevers over 39
degrees C was diagnosed with Stills disease. High doses of prednisone led to
resolution of symptoms, however after reducing the doses of prednisone to 15 mg,
high fevers over 39 degrees C returned, as well as joint pains. The high doses
of prednisone led to decompensation of diabetes mellitus even with 4 daily
insulin dosages. Therefore it was proceeded to regular subcutaneous
administration of anakinra once a day. Anakinra enabled the reduction of
prednisone to as much as the currently administered 2.5 mg a day, but it has not
so far allowed for removing glucocorticoids from the treatment completely.
Activity of the disease is shown by the findings within the FDG-PET/CT
examination. At the time of maximum activity of the disease there was distinct
lymphadenopathy with pathological accumulation of FDG visible as well as
increased accumulation of FDG in the hematopoietic bone marrow. As the disease
activity decreased, the size of nodules regressed and FDG accumulation in both
the lymphatic nodes and bone marrow declined. FDG-PET/CT is a suitable method for
monitoring the activity of Stills disease.Key words: anakinra - Adult-onset
Stills disease.
PMID- 29334751
TI - Pursuing excellence in ERCP.
AB - The term "ERCP cannulation" returns 1,563 items in Pubmed. In 1980 there were 7
papers, and 92 were included in 2015. Any gastroenterologist knows ERCP is often
a complex procedure, at times with uncertain results, that unfortunately leads
every so often to lawsuits. Most issues derive from attempts at biliary
cannulation, despite the improved instruments available since the days of the
first sphincterotomy back in 1974. The initial priority goal of ERCP learning is
a satisfactory rate of choledochal cannulation. Such rate has been somewhat
arbitrarily set as at least 80% of successful biliary access.
PMID- 29334752
TI - The road to registration: Aboriginal and Torres Strait Islander health
practitioner training in north Queensland.
AB - CONTEXT: In 2012, the new profession of Aboriginal and Torres Strait Islander
health practitioner (ATSIHP) was registered under the Health Practitioner
Regulation National Law Act 2009. The project in this present study evolved out
of the Australian Government?'s recognition of the need for the existing
Indigenous health worker (IHW) workforce to meet the minimum qualification
requirements for registration as ATSIHPs through recognition of prior learning
and/or further education. A total of 53 IHWs participated in the upskilling
project between June 2014 and June 2015, with approximately 200 IHWs from
Queensland expressing an interest in undertaking the training. This demonstrated
a clear need for further training programs such as this one. The project was
coordinated by the Indigenous Health Unit at James Cook University (JCU) with
training being delivered by TAFE Cairns in collaboration with the College of
Medicine and Dentistry, JCU. Students travelled from as far north as the Torres
Strait and as far west as Mount Isa. ISSUES: The key issues for discussion were
associated with the ATSIHP role being relatively new including the limited
preparedness of training providers to deliver the upgraded qualification
requirements and uncertainty about the registration process. Compounding this was
a general undervaluing and underutilisation of the IHW role within the current
primary healthcare system. Other challenges included the variations of IHW roles,
scope of practice and educational standards held by individuals, as well as the
associated complexities of providing training to IHWs from the large and diverse
geographic area that is rural and remote Australia. Program and student
evaluation was undertaken with each of the three cohorts via a course experience
questionnaire, TAFE evaluation forms and opportunistic student feedback. LESSONS
LEARNED: Lessons learned as a result of this project include the need to continue
to recognise and promote understanding of the contribution that IHW/ATSIHPs make
in improving health, the importance of conducting a comprehensive student
selection process, the benefits of working collaboratively between the university
and vocational education training sectors, the need to continue to strengthen
partnerships between higher education and health industry, the need for flexible
funding and training models that enable adequate learning support, and the
identification of a significant unmet training need.
PMID- 29334753
TI - Physicians' Perceptions of Hope and How Hope Informs Interactions With Patients:
A Qualitative, Exploratory Study.
AB - OBJECTIVES: Today some studies of physicians' perceptions of hope are available,
but not studies of how hope informs patient care. The objectives of this
qualitative study were to describe the ways physicians conceptualize hope and how
these may inform interactions with their patients. METHODS: Ten physicians
working in a large tertiary care teaching hospital were interviewed. They
represented palliative care, oncology, and 7 other specialties. Minimal amount of
background information was collected. In-depth interviews were conducted during
spring of 2016. Open coding and the constant comparison method were used to
identify emerging themes from the transcribed data. Validation method included
member checking. RESULTS: Hope was defined as an abstract, evolving concept
characterized by future-oriented wishes; offering possibilities for reframing and
shaping new meaning; an attitude of positivity or optimism; an attribute of the
human condition with emotional and relational roots; and as a response to the
existential inevitability of suffering and death. Three themes describing hope
emerged: "assessing hope," "fostering and sustaining hope," and "attributes and
outcomes of hope." CONCLUSIONS: The findings show how physicians conceptualize
hope and how these conceptions differ in the empirical light of the study.
Physicians' perceptions of "hope" may evolve when entering into a therapeutic
relationship exploring the needs and desires of patients. Physicians'
perspectives about "hope" may at times not be solely their own but are those of
their patients and thus resulting in an amalgamation, or a rebuilding/rekindling
of hope amidst hopelessness, that suits a particular relationship.
PMID- 29334754
TI - High Neutrophil to Lymphocyte Ratio Is Associated With Symptomatic and Ruptured
Thoracic Aortic Aneurysm.
AB - The predictive value of the neutrophil to lymphocyte ratio (NLR) has been
demonstrated in several cardiovascular diseases. The aim of our study was to
investigate the association between the preoperative NLR and aneurysm
characteristics as well as 30-day postoperative morbidity and mortality in
patients with thoracic aortic aneurysm (TAA) undergoing aortic surgical repair.
Consecutive patients (n = 75) with TAA were retrospectively included over a 10
year period. Clinical characteristics, aneurysm characteristics, and 30-day
postoperative outcome were recorded. The median age of patients was 71 (67-80)
years. The median preoperative NLR was 3.5 (2.3-5.8). The proportion of
asymptomatic TAA was significantly lower in patients with an NLR > 3.5 compared
with those with an NLR < 3.5 (52.6% vs 75.7%; P = .054). The proportion of
patients with pain or with ruptured TAA was significantly higher in patients with
an NLR > 3.5 compared with those with NLR < 3.5 (42.1% vs 16.2%; P = .022 and
26.3% vs 2.7%; P = .007, respectively). No significant difference was observed
regarding the 30-day overall postoperative mortality and morbidity. The
preoperative NLR did not correlate with TAA diameter. A high preoperative NLR is
significantly associated with symptomatic and ruptured TAA, suggesting a
potential interest as a marker and/or player in the disease.
PMID- 29334755
TI - Neuropathy in Diabetes: "One Cannot Begin It Too Soon".
PMID- 29334756
TI - Thioredoxin-1 Negatively Modulates ADAM17 Activity Through Direct Binding and
Indirect Reductive Activity.
AB - AIMS: A disintegrin and metalloprotease 17 (ADAM17) modulates signaling events by
releasing surface protein ectodomains such as TNFa and the EGFR-ligands. We have
previously characterized cytoplasmic thioredoxin-1 (Trx-1) as a partner of ADAM17
cytoplasmic domain. Still, the mechanism of ADAM17 regulation by Trx-1 is
unknown, and it has become of paramount importance to assess the degree of
influence that Trx-1 has on metalloproteinase ADAM17. RESULTS: Combining
discovery and targeted proteomic approaches, we uncovered that Trx-1 negatively
regulates ADAM17 by direct and indirect effect. We performed cell-based assays
with synthetic peptides and site-directed mutagenesis, and we demonstrated that
the interaction interface of Trx-1 and ADAM17 is important for the negative
regulation of ADAM17 activity. However, both Trx-1K72A and catalytic site mutant
Trx-1C32/35S rescued ADAM17 activity, although the interaction with Trx-1C32/35S
was unaffected, suggesting an indirect effect of Trx-1. We confirmed that the Trx
1C32/35S mutant showed diminished reductive capacity, explaining this indirect
effect on increasing ADAM17 activity through oxidant levels. Interestingly, Trx
1K72A mutant showed similar oxidant levels to Trx-1C32/35S, even though its
catalytic site was preserved. We further demonstrated that the general reactive
oxygen species inhibitor, Nacetylcysteine (NAC), maintained the regulation of
ADAM17 dependent of Trx-1 reductase activity levels; whereas the electron
transport chain modulator, rotenone, abolished Trx-1 effect on ADAM17 activity.
INNOVATION: We show for the first time that the mechanism of ADAM17 regulation,
Trx-1 dependent, can be by direct interaction and indirect effect, bringing new
insights into the cross-talk between isomerases and mammalian metalloproteinases.
CONCLUSION: This unexpected Trx-1K72A behavior was due to more dimer formation
and, consequently, the reduction of its Trx-1 reductase activity, evaluated
through dimer verification, by gel filtration and mass spectrometry analysis.
Antioxid. Redox Signal. 29, 717-734.
PMID- 29334757
TI - High Prevalence of Non-B HIV-1 Subtypes in Overseas Sailors and Prostitutes in
Korea.
AB - There have been no studies related to groups at the highest risk for HIV-1
infection in Korea before 1993. In this study, for the first time, we report the
distribution of HIV subtypes in overseas sailors (OSs) and prostitutes who worked
in brothels near U.S. military bases in Korea. We retrospectively determined the
sequences of nef in 131 patients using reverse transcription polymerase chain
reaction (RT-PCR). These patients composed of 102 OSs, 14 OS spouses, and 15
prostitutes. Phylogenetic analysis was performed using 128 Korean OSs, OS
spouses, and prostitutes. The distribution of non-B subtypes (n = 105) was as
follows: 39, CRF02_AG; 15, CRF01_AE; 7, A1; 7, A2; 6, D; 2, CRF06_cpx; 3, C; 6,
G; 11, untypable; and 1 each for CRF09_cpx, CRF12_BF, CRF50_A1D, A3, AFG, H, F1,
F2, and A. Of the 116 OSs and OS spouses, 101 (87%), 11 (9%), and 4 (3%) subjects
had non-B, Western B, and Korean subclade B (KSB) HIV-1s, respectively. Among the
15 prostitutes, 10 had Western B (67%), 4 non-B (27%), and 1 KSB (7%) HIV-1s. All
14 couples, each comprising of an OS and his spouse, had the same subtype. KSB
(5%) was detected in OSs and prostitutes in 1990 and 1994, respectively. Of the
131 patients analyzed in this study, 105 (80%), 21 (16%), and 5 (4%) were
infected with the non-B, Western B, and KSB subtypes of HIV, respectively. In
future, these data may provide an important foundation for analysis of HIV-1
subtypes in Korea.
PMID- 29334758
TI - Anticancer Thiosemicarbazones: Chemical Properties, Interaction with Iron
Metabolism, and Resistance Development.
AB - SIGNIFICANCE: During the past decades, thiosemicarbazones were clinically
developed for a variety of diseases, including tuberculosis, viral infections,
malaria, and cancer. With regard to malignant diseases, the class of alpha-N
heterocyclic thiosemicarbazones, and here especially 3-aminopyridine-2
carboxaldehyde thiosemicarbazone (Triapine), was intensively developed in
multiple clinical phase I/II trials. Recent Advances: Very recently, two new
derivatives, namely COTI-2 and di-2-pyridylketone 4-cyclohexyl-4-methyl-3
thiosemicarbazone (DpC) have entered phase I evaluation. Based on the strong
metal-chelating/metal-interacting properties of thiosemicarbazones, interference
with the cellular iron (and copper) homeostasis is assumed to play an important
role in their biological activity. CRITICAL ISSUES: In this review, we summarize
and analyze the data on the interaction of (alpha-N-heterocyclic)
thiosemicarbazones with iron, with the special aim of bridging the current
knowledge on their mode of action from chemistry to (cell) biology. In addition,
we highlight the difference to classical iron(III) chelators such as
desferrioxamine (DFO), which are used for the treatment of iron overload. FUTURE
DIRECTIONS: We want to emphasize that thiosemicarbazones are not solely removing
iron from the cells/organism. In contrast, they should be considered as iron
interacting drugs influencing diverse biological pathways in a complex and multi
faceted mode of action. Consequently, in addition to the discussion of
physicochemical properties (e.g., complex stability, redox activity), this review
contains an overview on the diversity of cellular thiosemicarbazone targets and
drug resistance mechanisms. Antioxid. Redox Signal. 00, 000-000.
PMID- 29334759
TI - Redox Nano-Architectures: Perspectives and Implications in Diagnosis and
Treatment of Human Diseases.
AB - SIGNIFICANCE: Efficient targeted therapy with minimal side-effects is the need of
the hour. Locally altered redox state is observed in several human ailments, such
as inflammation, sepsis, and cancer. This has been taken advantage of in
designing redox-responsive nanodrug carriers. Redox-responsive nanosystems open a
door to a multitude of possibilities for the control of diseases over other drug
delivery systems. Recent Advances: The first-generation nanotherapy relies on
novel properties of nanomaterials to shield the drug and deliver it to the
diseased tissue or organ. The second generation is based on targeting the drug or
diagnostic material to the diseased cell-specific receptors, or to a particular
organ to improve the efficacy of the drug. The third and the latest generation of
nanocarriers, the stimuli-responsive nanocarriers exploit the disease condition
or environment to specifically deliver the drug or diagnostic probe for the best
diagnosis and treatment. Several different kinds of stimuli such as temperature,
magnetic field, pH, and altered redox state-responsive nanosystems have educed
immense promise in the field of nanomedicine and therapy. CRITICAL ISSUES: We
describe the evolution of nanomaterial since its inception with an emphasis on
stimuli-responsive nanocarriers, especially redox-sensitive nanocarriers.
Importantly, we discuss the future perspectives of redox-responsive nanocarriers
and their implications. FUTURE DIRECTIONS: Redox-responsive nanocarriers achieve
a near-to-zero premature release of the drug, thus avoiding off-site toxicity
associated with the free drug. This bears great potential for the development of
more effective drug delivery with better pharmacokinetics and pharmacodynamics.
Antioxid. Redox Signal. 00, 000-000.
PMID- 29334760
TI - Polymorphisms in Estrogen Synthesis Genes and Symptom Clusters During the
Menopausal Transition and Early Postmenopause: Observations From the Seattle
Midlife Women's Health Study.
AB - During the menopausal transition and early postmenopause, participants in the
Seattle Midlife Women's Health Study (SMWHS) experienced one of the three symptom
severity clusters identified through latent class analysis: severe hot flashes
with moderate sleep, mood, cognitive, and pain symptoms (high-severity hot
flash); low-severity hot flashes with moderate levels of all other symptom groups
(moderate severity); and low levels of all symptom groups (low severity). In an
effort to determine whether gene polymorphisms were associated with these symptom
severity classes, we tested associations between gene polymorphisms in the
estrogen synthesis pathways (cytochrome P450 19 [CYP 19] and 17 beta
hydroxysteroid dehydrogenase [ 17HSDB1]) and the three symptom severity clusters.
SMWHS participants ( N = 137) recorded symptoms monthly in diaries and provided
buccal smears for genotyping. Multilevel latent class analysis with multinomial
regression was used to determine associations between gene polymorphisms and
symptom severity clusters. Only the 17HSDB1 polymorphisms ( rs615942 and
rs592389) were associated significantly with the high-severity hot flash cluster
versus the low-severity symptom cluster. None of the polymorphisms was associated
with the moderate-severity cluster versus the low-severity symptom cluster.
Findings of associations of the 17HSDB1 polymorphisms with the high-severity hot
flash symptom cluster are consistent with those of an association between 17HSDB1
polymorphisms and hot flashes in the Study of Women and Health Across the Nation
population and our previous findings of associations between these polymorphisms
with greater estrone levels.
PMID- 29334761
TI - Regulation of Cancer and Cancer-Related Genes via NAD.
AB - SIGNIFICANCE: NAD+ is an essential redox cofactor in cellular metabolism and has
emerged as an important regulator of a wide spectrum of disease conditions, most
notably, cancers. As such, various strategies targeting NAD+ synthesis in cancers
are in clinical trials. Recent Advances: Being a substrate required for the
activity of various enzyme families, especially sirtuins and poly(adenosine
diphosphate [ADP]-ribose) polymerases, NAD+-mediated signaling plays an important
role in gene expression, calcium release, cell cycle progression, DNA repair, and
cell proliferation. Many strategies exploring the potential of interfering with
NAD+ metabolism to sensitize cancer cells to achieve anticancer benefits are
highly promising, and are being pursued. CRITICAL ISSUES: With the multifaceted
roles of NAD+ in cancer, it is important to understand how cellular processes are
reliant on NAD+. This review summarizes how NAD+ metabolism regulates various
pathophysiological processes in cancer, and how this knowledge can be exploited
to devise effective anticancer therapies in clinical settings. FUTURE DIRECTIONS:
In line with the redundant pathways that facilitate NAD+ metabolism, further
studies should comprehensively understand the roles of the various NAD+
synthesizing as well as NAD+-utilizing biomolecules to understand its true
potential in cancer treatment. Antioxid. Redox Signal. 00, 000-000.
PMID- 29334762
TI - Altered Redox State Modulates Endothelial KCa2.3 and KCa3.1 Levels in Normal
Pregnancy and Preeclampsia.
AB - AIMS: Altered redox state has been related to the development of normal pregnancy
(NP) and preeclampsia (PE). Endothelial KCa2.3 and KCa3.1 (KCas) play an
important role in vasodilation, and KCas levels are affected by oxidative stress.
We investigated the mechanisms of oxidative stress-mediated KCas expression
modulation during NP and PE. RESULTS: Human uterine microvascular endothelial
cells were incubated in serum from normal nonpregnant women (n = 13) and women
with NP (n = 24) or PE (n = 15), or in vascular endothelial growth factor (VEGF),
oxidized low-density lipoprotein (ox-LDL), progesterone, or estradiol-17beta (E2)
containing medium for 24 h. NP serum elevated H2O2 levels via reducing catalase
and glutathione peroxidase 1 levels, thereby enhancing KCas levels via a
H2O2/fyn/extracellular signal-regulated kinase (ERK)-mediated pathway. VEGF
enhanced H2O2 and KCas levels and KCa3.1 currents. KCas were upregulated and KCas
activation-induced endothelium-dependent relaxation (EDR) was augmented in
vessels from pregnant mice and rats. Whereas PE serum, ox-LDL, progesterone, or
soluble fms-like tyrosine kinase 1 (sFlt-1) elevated superoxide levels via
elevating NADPH oxidase 2 (NOX2) and NOX4 levels and reducing superoxide
dismutase (SOD) 1 levels, thereby downregulating KCas. sFlt-1 inhibited EDR. PE
serum- or progesterone-induced alterations in levels of KCas were reversed by
polyethylene glycol-SOD, NOX inhibition, or E2. Innovation and Conclusions: This
is the first study of how endothelial KCas levels are modulated during NP and PE.
KCas were upregulated by soluble serum factors such as VEGF via H2O2 generation
in NP, and were downregulated by serum factors such as progesterone and ox-LDL
via superoxide generation in PE, which may contribute to hemodynamic adaptations
in NP or to the development of PE. Antioxid. Redox Signal. 00, 000-000.
PMID- 29334763
TI - Long Noncoding RNA LINC01619 Regulates MicroRNA-27a/Forkhead Box Protein O1 and
Endoplasmic Reticulum Stress-Mediated Podocyte Injury in Diabetic Nephropathy.
AB - AIMS: Altered activities of long noncoding RNAs (lncRNAs) have been implicated in
the regulation of microRNAs. microRNA-27a (miR-27a) upregulation has been shown
to induce endoplasmic reticulum (ER) stress podocyte injury in diabetic
nephropathy (DN). Herein, we aim to interrogate the mutually regulated network of
miR-27a with long intergenic noncoding RNA 1619 (LINC01619) and the target gene.
RESULTS: LINC01619 downregulation was found in human DN renal biopsy tissues and
contributed to proteinuria and diminished renal function. LINC01619 was expressed
in podocyte cytoplasm and involved in ER stress signaling pathway. LINC01619
exerted biological function by serving as a "sponge" for miR-27a, which
negatively targeted forkhead box protein O1 (FOXO1) and activated ER stress. In
diabetic rats and high-glucose cultured podocytes, LINC01619 triggered oxidative
stress and podocyte injuries as demonstrated by increased apoptosis, diffuse
podocyte foot process effacement, and decreased renal function. Innovation and
Conclusion: This study demonstrates that LINC01619 functions as a competing
endogenous RNA and regulates miR-27a/FOXO1-mediated ER stress and podocyte injury
in DN. Antioxid. Redox Signal. 29, 355-376.
PMID- 29334764
TI - Development of Gene Therapeutics for Head and Neck Cancer in China: From Bench to
Bedside.
AB - Head and neck cancer represents the seventh most common cancer worldwide.
Although multidisciplinary sequential treatments have been used, there is still
an urgent need for new treatment approaches that can effectively improve the
outcomes of patients with advanced stages of head and neck cancer. Gene therapy
is a rapidly evolving field in cancer therapy that has been shown to improve the
efficacy of antitumor treatment. China is at the forefront in clinical trials and
practice of gene therapy. Chinese researchers have mainly focused on gene
therapeutics based on oncolytic virus and recombinant adenovirus expressing p53,
antiangiogenesis factor or herpes simplex virus-thymidine kinase. Currently, two
gene therapy drugs, Gendicine and Oncorine, have been marketed in China, and a
number of upcoming gene therapy agents are under development for the treatment of
head and neck cancer. Most gene therapy agents have demonstrated excellent
tolerance. However, the therapeutic effects need further improvement. With
current innovations in tumor biology and knowledge, gene therapy has great
potential as a safe and effective anticancer treatment. In recent years, new gene
therapy agents with promising effects have been incorporated into clinical trials
in China. Thus, gene therapy may become an important part of anticancer therapy
and is expected to improve the therapeutic effect of head and neck cancers in the
near future.
PMID- 29334765
TI - Examining Use of Mobile Phones for Sleep Tracking Among a National Sample in the
USA.
AB - Mobile technology has been designed to serve a number of functions relating to
health, but we know little about individuals who use these tools to track sleep.
This study utilized data from a cross-sectional, geographically diverse survey of
adults in the USA (N = 934). Among the sample, 28.2% (n = 263) report current use
of a mobile phone for sleep tracking. Income and gender were significant
correlates of sleep tracking (p < 0.05). Compared to a poor diet, a reported
"excellent" diet was associated with sleep tracking (p < 0.05). Interestingly,
compared to individuals who never smoke, report of smoking "everyday" was
associated with sleep tracking (p < 0.05). Finally, individuals who reported
current use of their mobile device for other health functions (e.g., chat with
their doctor or log symptoms) were more likely to report sleep tracking on their
mobile device (p < 0.05). Results appear to suggest sleep tracking is common
among individuals with good general health.
PMID- 29334766
TI - AJMQ Newsletter: Register Now! Medical Quality 2018: Improving Population Health
Through Health Equity and Patient Advocacy.
PMID- 29334767
TI - A novel adaptive algorithm for 3D finite element analysis to model extracortical
bone growth.
AB - Extracortical bone growth with osseointegration of bone onto the shaft of massive
bone tumour implants is an important clinical outcome for long-term implant
survival. A new computational algorithm combining geometrical shape changes and
bone adaptation in 3D Finite Element simulations has been developed, using a soft
tissue envelope mesh, a novel concept of osteoconnectivity, and bone remodelling
theory. The effects of varying the initial tissue density, spatial influence
function and time step were investigated. The methodology demonstrated good
correspondence to radiological results for a segmental prosthesis.
PMID- 29334768
TI - Angular and metric analysis of the neural structures in the cerebellopontine
angle.
AB - INTRODUCTION: The cerebellopontine angle (CPA) is a subarachnoid space in the
lateral aspect of the posterior fossa. In this study, we propose a complementary
analysis of the CPA from the cerebellopontine fissure. METHODS: We studied 50
hemi-cerebelli in the laboratory of neuroanatomy and included a description of
the CPA anatomy from the cerebellopontine fissure and its relationship with the
flocculus and the 5th, 6th, 7th, and 8th cranial nerves (CN) origins. RESULTS:
The average distance from the 5th CN to the mid-line (ML) was 19.2 mm, 6th CN to
ML was 4.4 mm, 7-8 complex to ML was 15.8 mm, flocculus to ML was 20.5 mm, and
flocculus to 5th CN was 11.5 mm, additionally, and the diameter of the flocculus
was 9.0 mm. The angle between the vertex in the flocculus and the V CN and the
medullary-pontine line was 64.8 degrees. DISCUSSION: The most common access to
the CPA is through the retrosigmoid-suboccipital region and this approach can be
done with the help of an endoscope. The anatomy of origins of neural structures
tends to be preserved in cases of CPA lesions. CONCLUSION: Knowledge of the
average distances between the neural structures in the cerebellar-pontine fissure
and the angular relationships between these structures facilitates the use of
surgical approaches such as microsurgery and endoscopy.
PMID- 29334769
TI - Topographic Analysis of the Distal Femoral Condyle Articular Cartilage Surface:
Adequacy of the Graft from Opposite Condyles of the Same or Different Size for
the Osteochondral Allograft Transplantation.
AB - Objective To analyze the topography of the opposite condyle to treat focal
femoral condyle articular defects with an osteochondral allograft (OCA). Design
Three groups were created: Group 1, same condyle with same width; Group 2,
opposite condyle with same width; Group 3, opposite condyle with different width.
Computed tomography (CT) of 22 cadaveric femoral hemi-condyles was used to create
3-dimensional CT models that were exported into point-cloud models. Three zones
of the donor condyle (anterior, middle, and posterior) were quantified. Four
defect sizes were created (15, 18, 23, 25 mm) at the weight-bearing region. The
defect was moved throughout each donor condyle zone and the least distance was
calculated, defined as the shortest distance between the defect and the donor
condyle. Results The mean least distance increased with larger defect size in all
groups, yet there was a less than 0.2 mm difference in the least distance among
defect sizes. The 15, 18, and 23 mm defect models in Group 1 exhibited greater
least distances at the anterior than middle and posterior zones. The 15 mm defect
model exhibited greater least distance at the anterior zone than posterior zone
in Group 3. However, there was a less than 0.05 mm difference in the mean least
distance between zones. There was no significant difference in the least distance
between groups. Conclusion OCAs from opposite condyles yield similar topographic
matching to OCAs from the same condyles, suggesting that opposite condyles can be
utilized. Clinical correlation and outcomes are necessary.
PMID- 29334770
TI - Student Perceptions of Collaboration Skills in an Interprofessional Context:
Development and Initial Validation of the Self-Assessed Collaboration Skills
Instrument.
AB - An integral component of interprofessional education (IPE) is the development of
a collaboration-ready health-care workforce. While collaboration is a fundamental
element of IPE, there is no existing measure of collaboration skills that is not
context specific. This article describes the development and initial validation
of the Self-Assessed Collaboration Skills (SACS) measure. Items were initially
drawn from the Collaboration Skills Assessment Tool rubric, an educational
assessment tool. The SACS measure was piloted in a sample of students in an
introductory IPE course. Following scale revision, the SACS was piloted a second
time in a sample of students in an IPE health systems course and then validated
in a sample of students in an introductory IPE course. Exploratory factor
analysis was used to assess scale factor structure in Pilots 1 and 2 and
confirmatory factor analysis to confirm factor structure in the validation
sample. Convergent and discriminant validity were also assessed. The final SACS
measure is an 11-item scale consisting of three dimensions of collaboration:
information sharing, learning, and team support. The SACS measure demonstrates
high internal consistency and both convergent and discriminant validity as a
measure of collaboration. The SACS can be implemented in any setting for
assessing collaboration in clinical and nonclinical contexts.
PMID- 29334772
TI - Spontaneous regression of a large skull base meningioma: case report.
AB - We present the case of a 58 year old lady with a large middle cranial fossa
meningioma (5 cm * 4 cm in maximal dimensions) which has considerably regressed
without any treatment during seven years of follow up. While the tumour had
remained radiologically static for the first three years, scans from year five
post-diagnosis onwards have shown shrinkage of the meningioma from a calculated
volume of 36 cm3 to 11.2 cm3. There has been no intratumoral haemorrhage or
infarction and no medication or exogenous hormonal effect that could account for
this effect. We reviewed the literature and report that this is only the second
ever case of spontaneous regression of meningioma.
PMID- 29334771
TI - Development of Anti-Human Mesothelin-Targeted Chimeric Antigen Receptor Messenger
RNA-Transfected Peripheral Blood Lymphocytes for Ovarian Cancer Therapy.
AB - CD19-targeted chimeric antigen receptor (CAR) engineered T/natural killer (NK)
cell therapies can result in durable clinical responses in B-cell malignancies.
However, CAR-based immunotherapies have been much less successful in solid
cancers, in part due to "on-target off-tumor" toxicity related to expression of
target tumor antigens on normal tissue. Based on preliminary observations of
safety and clinical activity in proof-of-concept clinical trials, tumor antigen
specific messenger RNA (mRNA) CAR transfection into selected, activated, and
expanded T/NK cells may permit prospective control of "on-target off-tumor"
toxicity. To develop a commercial product for solid tumors, mesothelin was
selected as an antigen target based on its association with poor prognosis and
overexpression in multiple solid cancers. It was hypothesized that selecting,
activating, and expanding cells ex vivo prior to mRNA CAR transfection would not
be necessary, thus simplifying the complexity and cost of manufacturing. Now, the
development of anti-human mesothelin mRNA CAR transfected peripheral blood
lymphocytes (CARMA-hMeso) is reported, demonstrating the manufacture and
cryopreservation of multiple cell aliquots for repeat administrations from a
single human leukapheresis. A rapid, automated, closed system for cGMP-compliant
transfection of mRNA CAR in up to 20 * 109 peripheral blood lymphocytes was
developed. Here we show that CARMA-hMeso cells recognize and lyse tumor cells in
a mesothelin-specific manner. Expression of CAR was detectable over approximately
7 days in vitro, with a progressive decline of CAR expression that appears to
correlate with in vitro cell expansion. In a murine ovarian cancer model, a
single intraperitoneal injection of CARMA-hMeso resulted in the dose-dependent
inhibition of tumor growth and improved survival of mice. Furthermore, repeat
weekly intraperitoneal administrations of the optimal CARMA-hMeso dose further
prolonged disease control and survival. No significant off-target toxicities were
observed. These data support further investigation of CARMA-hMeso as a potential
treatment for ovarian cancer and other mesothelin-expressing cancers.
PMID- 29334773
TI - MACF1 Overexpression by Transfecting the 21 kbp Large Plasmid PEGFP-C1A-ACF7
Promotes Osteoblast Differentiation and Bone Formation.
AB - Microtubule actin crosslinking factor 1 (MACF1) is a large spectraplakin protein
known to have crucial roles in regulating cytoskeletal dynamics, cell migration,
growth, and differentiation. However, its role and action mechanism in bone
remain unclear. The present study investigated optimal conditions for effective
transfection of the large plasmid PEGFP-C1A-ACF7 (~21 kbp) containing full-length
human MACF1 cDNA, as well as the potential role of MACF1 in bone formation. To
enhance MACF1 expression, the plasmid was transfected into osteogenic cells by
electroporation in vitro and into mouse calvaria with nanoparticles. Then,
transfection efficiency, osteogenic marker expression, calvarial thickness, and
bone formation were analyzed. Notably, MACF1 overexpression triggered a drastic
increase in osteogenic gene expression, alkaline phosphatase activity, and matrix
mineralization in vitro. Mouse calvarial thickness, mineral apposition rate, and
osteogenic marker protein expression were significantly enhanced by local
transfection. In addition, MACF1 overexpression promoted beta-catenin expression
and signaling. In conclusion, MACF1 overexpression by transfecting the large
plasmid containing full-length MACF1 cDNA promotes osteoblast differentiation and
bone formation via beta-catenin signaling. Current data will provide useful
experimental parameters for the transfection of large plasmids and a novel
strategy based on promoting bone formation for prevention and therapy of bone
disorders.
PMID- 29334774
TI - Three column osteotomy for adult spine deformity: comparison of outcomes and
complications between kyphosis and kyphoscoliosis.
AB - BACKGROUND: To compare the surgical outcomes and complications between kyphosis
and kyphoscoliosis when using three-column osteotomies. METHODS: Adult spine
deformity (ASD) patients with three column osteotomies from March 2005 to
December 2014 in our center were retrospectively reviewed. Pre- and postoperative
standing postero-anterior and lateral radiographs of the entire spine were
obtained. Scoliosis Research Society-22 questionnaire [SRS-22] and Oswestry
Disability Index [ODI] were administered preoperatively, postoperatively (surveys
within 2 months after surgery), and at final follow-up. Patients were assigned to
one of two groups according to pre-operative coronal curve magnitude: (1) if
coronal curve <10 degrees , patients were assigned to kyphosis group (K group);
(2) if coronal curve >40 degrees , patients were assigned to kyphoscoliosis group
(S group). RESULTS: 33 ASD patients were assigned to the kyphosis group (K
group), of which 26 received PSO (pedicle subtraction osteotomy) and 7 VCR
(vertebral column resection). 76 patients were assigned to kyphoscoliosis group
(S group), of which 50 received PSO and 26 VCR. Patients in the K group were
significantly older than in the S group (42.8 vs. 33.7 years, p < .05).
Significantly longer OT (operation time) and more EBL (estimated blood loss) were
observed in the S group as compared to K group (OT: 282 vs. 205 min, p < .05;
EBL: 1827 vs. 1214ml, p < .05). No significant difference was noted for number of
fusion levels between the groups (12.4 vs. 12.7, p > .05). Pre-operative
radiographic parameters demonstrated no difference of GK (global kyphosis) and
SVA (sagittal vertical axis) between the two groups (GK: 74.7 degrees vs 76.2
degrees , p > .05; SVA:53.2 vs. 55.7mm, p > .05). K group had larger KF than S
group (26% vs. 15%, p < .05). Overall complication rate was higher in S group
than in K group (30.3% vs. 18.2%, p < .05). No difference of neurological
complication rates between the two groups (9.1% vs. 10.5%, p > .05). CONCLUSIONS:
Kyphoscoliosis group had less KF, GK correction and more OT, EBL and surgical
complications when receiving three column osteotomies.
PMID- 29334775
TI - Resistance to Acetaminophen Interference in a Novel Continuous Glucose Monitoring
System.
AB - Acetaminophen (APAP) can cause erroneously high readings in real-time continuous
glucose monitoring (rtCGM) systems. APAP-associated bias in an investigational
rtCGM system (G6) was evaluated by taking the difference in glucose measurements
between rtCGM and YSI from 1 hour before to 6 hours after a 1-g oral APAP dose in
66 subjects with type 1 or type 2 diabetes. The interference effect was defined
as the average post-dose (30-90 minutes) bias minus the average baseline bias for
each subject. The clinically meaningful interference effect was defined as 10
mg/dL. The G6 system's overall mean (+/-SD) interference effect was 3.1 +/- 4.8
mg/dL (one-sided upper 95% CI = 4.1 mg/dL), significantly lower than 10 mg/dL.
The G6 system's resistance to APAP interference should provide reassurance to
those using the drug.
PMID- 29334776
TI - Multiple intracranial aneurysms in a patient with type I Gaucher disease: a case
report and literature review.
AB - Multiple intracranial aneurysms (IAs) have never been reported in a patient with
Gaucher disease (GD). A 69-year-old-female with type I GD presented with a left
sixth nerve palsy due to a large posterior inferior cerebellar artery (PICA)
aneurysm. Cerebral angiography demonstrated fifteen unruptured IAs (UIAs).
PMID- 29334777
TI - Endovascular implantation of 125I seed combined with transcatheter arterial
chemoembolization for unresectable hepatocellular carcinoma.
AB - AIM: The purpose of this study was to evaluate the efficacy and safety of the
endovascular implantation of 125I seed under ultrasound and x-ray guidance
combined with transcatheter arterial chemoembolization (TACE) for hepatocellular
carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). PATIENTS &
METHODS: The study included 134 pathologically proven or clinically confirmed
primary HCC patients with PVTT in our hospital from January 2013 to June 2015.
RESULTS & CONCLUSION: Compared with the TACE treatment alone, the combination
therapy of 125I seed implantation with TACE significantly prolonged the median
survival time and improved the 6-, 12- and 18-month survival rates for HCC
patients with PVTT. In addition, the type III PVTT and tumor size were
independent predictors for poor prognosis of HCC patients with PVTT.
PMID- 29334778
TI - Fluid Dynamic Analysis of Hand-Pump Infuser and UROMAT Endoscopic Automatic
System for Irrigation Through a Flexible Ureteroscope.
AB - INTRODUCTION: To evaluate the flow characteristics produced by a manual and
automated-pump irrigation system connected to a flexible ureteroscope. MATERIALS
AND METHODS: An in vitro analysis of a manual hand-pump infuser (HP) and the
UROMAT Endoscopic Automatic System for Irrigation(r) (E.A.S.I.) pump was
performed. Standard irrigation tubing was used to connect a three-way valve to a
flexible ureteroscope, the irrigation system, and a digital manometer. Flow rate
and irrigation pressure measurements were recorded over a 15-minute period using
pressure settings of 150 and 200 mm Hg for both irrigation pump systems. Once the
HP was inflated to the initial pressure, it was not reinflated over the course of
the trial. Data were collected with the working channel unoccupied and with
placement of a 200 MUm (0.6F) holmium laser fiber, 1.7F nitinol stone retrieval
basket, or 2.67F guidewire. RESULTS: The difference in pressure measured at the
site of inflow of irrigation to the ureteroscope was significantly greater using
the HP compared to the E.A.S.I. pump at pressure settings of 150 mm Hg with and
without the use of ureteroscopic instrumentation (p < 0.001), and at 200 mm Hg
with instrumentation in the working channel (p < 0.01). There was no significant
difference in the flow rate of irrigation through the open-channel ureteroscope
over the course of 5 minutes between the two pump systems. CONCLUSION: The flow
rates of irrigation produced by the HP and the E.A.S.I. pump are similar at
pressures of 150 and 200 mm Hg irrespective of the occupancy of a ureteroscope's
working channel during the first 5-minutes of irrigation. Irrigation pressure at
the entry site of the ureteroscope is subject to significant variability with use
of the HP compared to the E.A.S.I. pump irrigation system.
PMID- 29334779
TI - Extra-articular tenosynovial giant cell tumor of diffuse type in the temporal
area with brain parenchymal invasion: a case report.
AB - Tenosynovial giant cell tumor of diffuse type is a locally aggressive neoplasm
that most commonly arises in the lower extremities. Herein, we report for the
first time a case of an extra-articular tenosynovial giant cell tumor of diffuse
type in the temporal region with brain parenchymal invasion. Imaging studies
revealed an intracranial expansile mass in the temporal bone without involvement
of the temporomandibular joint. The unusual location of the tumor without
involvement of the joint and the presence of brain parenchymal invasion made this
case challenging to diagnose.
PMID- 29334781
TI - Correction to: Coulter et al., Real-time symptom reporting during elective
intracranial pressure monitoring using an interactive handset.
PMID- 29334780
TI - Rules governing the mechanism of epigenetic reprogramming memory.
AB - AIM: Disclosing the mechanisms that regulate reprogramming memory. MATERIALS &
METHODS: We established computational procedure to find DNA methylation somatic
memory sites (SMSs) at single CpGs and integrated them with genomics,
epigenomics, transcriptomics and imprinting information. RESULTS & CONCLUSION:
Reprogramming memory persists at late passages in low methylated regions.
Contrarily to hypomethylated, hypermethylated SMSs occur at evolutionary
conserved sites overlapping active transcription loci in dynamic chromatin
regions. The epigenetic-memory molecular origin is the expression of source-cell
transcription factors protecting hypomethylated SMSs in euchromatin from de novo
methylation, keeping source-cell lineage-specific loci in induced pluripotent
stem (iPS) cells incompletely silenced. Sites in lineage-specific genes of
different-from-those-of-the-source-cell lineages remain hypermethylated in
heterochromatin regions becoming permanently silenced. SMSs cause differential
expression between iPS cells and embryonic stem cells through two mechanisms:
'epigenetic/expression memory rule', the DNA unreprogramming methylation status
coupled with chromatin states induces differentially expressed genes. 'Imprinting
control', the change of DNA methylation status in imprinting control regions
induces differential expression of imprinted genes.
PMID- 29334782
TI - Outcomes of Bilateral vs Unilateral Ankle Arthrodesis.
AB - BACKGROUND: While ankle arthrodesis is a common treatment for severe ankle
osteoarthritis, performing bilateral ankle arthrodesis is controversial because
of associated problems, such as severe gait abnormality and bilateral loss of
talocrural joint motion. Furthermore, few reports exist regarding the detailed
outcomes of bilateral ankle arthrodesis. Therefore, we aimed to compare the
outcomes of bilateral ankle arthrodesis with those of unilateral ankle
arthrodesis, using both subjective and objective assessments. METHODS: The data
from 20 patients (10 each in the bilateral and unilateral groups), who underwent
arthrodesis between 2005 and 2015, were retrospectively reviewed. The minimum
follow-up duration was 2 years. Radiographic outcomes were assessed using
radiographs and computed tomography. Clinical outcomes were assessed using the
Japanese Society for Surgery of the Foot (JSSF) scale and the Self-Administered
Foot Evaluation Questionnaire (SAFE-Q). RESULTS: With the numbers available, no
significant group differences were observed for any of the patient
characteristics or postoperative range of motion. Mean JSSF scale scores
significantly improved in both groups ( P < .001); however, scores on the SAFE-Q
subscale for "social functioning" were significantly lower in the bilateral group
compared to the unilateral group ( P = .049). CONCLUSIONS: Within the limitations
of the current study design, bilateral ankle arthrodesis did not appear to be
inferior to unilateral ankle arthrodesis, with the possible exception of social
functioning ability. Thus, bilateral ankle arthrodesis can be considered a viable
treatment option. LEVEL OF EVIDENCE: Level III, retrospective cohort study.
PMID- 29334783
TI - Frailty: A global measure of the multisystem impact of COPD.
AB - Chronic obstructive pulmonary disease (COPD) is a multisystem disease that
resembles the accumulation of multiple impairments seen in aging. A comprehensive
geriatric assessment (CGA) captures multisystem deficits, from which a frailty
index (FI) can be derived. We hypothesized that patients with COPD would be
frailer than a comparator group free from respiratory disease. In this cross
sectional analysis, the CGA questionnaire was completed and used to derive an FI
in 520 patients diagnosed with COPD and 150 comparators. All subjects were
assessed for lung function, body composition, 6-minute walking distance (6MWD),
and handgrip strength. Patients completed validated questionnaires on health
related quality of life and respiratory symptoms. Patients and comparators were
similar in age, gender, and body mass index, but patients had a greater mean +/-
SD FI 0.16 +/- 0.08 than comparators 0.05 +/- 0.03. In patients, a stepwise
linear regression 6MWD ( beta = -0.43), number of comorbidities ( beta = -0.38),
handgrip ( beta = -0.11), and number of exacerbations ( beta = 0.11) were
predictors of frailty (all p < 0.01). This large study suggests patients with
COPD are frailer than comparators. The FI derived from the CGA captures the
deterioration of multiple systems in COPD and provides an overview of
impairments, which may identify individuals at increased risk of morbidity and
mortality in COPD.
PMID- 29334784
TI - Unilateral lag screw fixation of isolated non-union atlas lateral mass fracture:
a new technical note.
AB - We describe a novel and new technique of posterior unilateral lag screw fixation
of non-union atlas lateral mass fracture. A 46-year-old man presented with
cervical pain and tenderness after a vehicle turn over accident and he was
diagnosed to have left atlas lateral mass fracture. He was initially treated by
immobilization using Minerva orthosis. About 2 months later, he developed severe
neck pain and limitation of motion and thus he was scheduled for operation due to
non-union atlas lateral mass fracture. A 28 mm lag screw was inserted under
anterior-posterior and lateral fluoroscopic views. The entrance point was at the
dorsal aspect of left atlas posterior arc at its junction to the lateral mass,
and by using the trajectory of 10 degrees medial and 22 degrees cephalad fracture
reduction was achieved. Unilateral lag screw fixation of atlas fractures is an
appropriate, safe and effective surgical technique for the management of
unilateral atlas fractures.
PMID- 29334785
TI - The use of combination immunotherapies as front-line therapy for non-small-cell
lung cancer.
PMID- 29334786
TI - Acute-on-chronic liver failure in chronic hepatitis B: an update.
AB - INTRODUCTION: Acute-on-chronic liver failure is a common pattern of end-stage
liver disease in clinical practice and occurs frequently in patients with chronic
hepatitis B or HBV-related cirrhosis. New progress in recent years leads to a
better understanding of this disease. Areas covered: This review updates the
current comprehensive knowledge about HBV-ACLF from epidemiological studies,
experimental studies, and clinical studies and provide new insights into the
definition, diagnostic criteria, epidemiology, nature history, pathogenesis,
treatment and prognostication of HBV-ACLF. Expert commentary: Patients with
chronic hepatitis B or HBV-related cirrhosis are at risk of developing acute-on
chronic liver failure, with multi-organ failure and high short-term mortality.
The precipitating events can be intra-hepatic or extra-hepatic and the underlying
chronic liver injury can be cirrhotic or non-cirrhotic. Host and viral factors
contribute to the susceptibility of developing HBV-ACLF. Systemic inflammation is
the driver of HBV-ACLF, which can be attributed to non-sterile and sterile
factors. Liver transplantation is the definitive treatment for HBV-ACLF. Cell
therapy is a promising alternative to LT, but requires validation and still has
concern of long-term safety. Other medical therapies, such as nucleoside
analogue, artificial liver supporting and glucocorticoid may improve survival in
a specific subgroup. New scoring systems improve the accuracy of prognostication
in HBV-ACLF, which is critical for early identification of candidates for LT.
PMID- 29334787
TI - Analysis of endocannabinoid receptors and enzymes in the post-mortem motor cortex
and spinal cord of amyotrophic lateral sclerosis patients.
AB - OBJECTIVE: We have investigated the endocannabinoid system in the motor cortex of
motor neuron disease (MND) patients. METHODS: Post-mortem samples from MND
patients and controls were used for immunostaining and/or Western blotting
analysis of endocannabinoid elements. RESULTS: We did not find any evidence of
neuronal losses in the motor cortex of MND patients, but elevations in glial
markers Iba-1 and GFAP were evident. We found no changes in FAAH and MAGL enzymes
and in the CB1 receptor, which correlated with the lack of cortical neuron death.
By contrast, the Western blotting analysis of CB2 receptors proved an increase in
the motor cortex corroborated by immunostaining, correlating with the elevated
gliosis in these patients. Double-labeling analyses revealed that this elevated
CB2 receptor immunostaining was located in GFAP-labelled astroglial cells.
However, we also found CB2 receptor labeling in cortical neurons confirmed with
double immunofluorescence with the neuronal marker MAP-2. This was also found in
the spinal cord, using double-labeling with the spinal motor neuron marker
choline-acetyl transferase. This happened in both patients and controls, despite
these neurons experienced an important degeneration in patients reflected in
reduced Nissl staining, TDP-43 immunostaining and CB1 receptor levels measured by
Western blotting. CONCLUSION: We have confirmed that CB2 receptors are elevated
in the motor cortex of MND patients associated with the reactive gliosis. This
phenomenon is previous to neuronal losses. We also found CB2 receptors in
cortical and spinal motor neurons. These observations support that targeting this
receptor may serve for developing neuroprotective therapies in MNDs.
PMID- 29334788
TI - Latissimus Dorsi Flap in Breast Reconstruction: Recent Innovations in the
Workhorse Flap.
AB - BACKGROUND: Surgeons employ the latissimus dorsi flap (LDF) for reconstruction of
a large variety of breast cancer surgery defects, including quadrantectomy,
lumpectomy, modified radical mastectomy, and others. The LDF may be used in
delayed or immediate reconstruction, in combination with tissue expanders for a
staged reconstruction, with implant-based immediate reconstruction, or alone as
an autogenous flap. METHODS: The authors discuss the historical uses and more
recent developments in the LDF. More recent advancements, including the
"scarless" approach and augmentation with the thoracodorsal artery perforator
flap, are discussed. RESULTS: The LDF is a reliable means for soft tissue
coverage providing form and function during breast reconstruction with acceptable
perioperative and long-term morbidities. CONCLUSIONS: When there is a paucity of
tissue, the LDF can provide tissue volume in autologous reconstruction, as well
as a reliable vascular pedicle for implant-based reconstruction as in the setting
of irradiated tissue.
PMID- 29334789
TI - Circular RNA expression in ovarian endometriosis.
AB - AIM: Circular RNAs (circRNAs) with miRNA response elements (MREs) could function
as competing endogenous RNA (ceRNA) in regulating gene expression. This study was
carried out to identify the expression profile and role of circRNAs in
endometriosis. MATERIALS & METHODS: Microarray assay was performed in four paired
ovarian endometriomas and eutopic endometrium, followed by quantitative real-time
RT-PCR in 24 paired samples. Bioinformatical algorithms were used to predict
MREs, as well as ceRNA and KEGG pathway analysis. RESULTS: We identified 262
upregulated and 291 downregulated circRNAs, binding with 1225 MREs. The ceRNA
network included 122 miRNAs and 137 mRNAs, which are involed in nine pathways.
CONCLUSION: CircRNAs are differentially expressed in endometriosis, which might
be related with pathogenesis of endometriosis.
PMID- 29334790
TI - Cognitive work hardening for return to work following depression: An intervention
study: Le reentrainement cognitif au travail pour favoriser le retour au travail
a la suite d'une depression : etude d'intervention.
AB - BACKGROUND: Work absences due to depression are prevalent; however, few
interventions exist to address the return-to-work challenges following a
depressive episode. PURPOSE: This mixed-methods study aimed to (a) evaluate the
effectiveness of cognitive work hardening in preparing people with depression to
return to work and (b) identify key elements of the intervention. METHOD: A
single group ( n = 21) pretest-posttest study design was used incorporating self
report measures (Work Ability Index, Multidimensional Assessment of Fatigue, Beck
Depression Inventory II) with interviews at intervention completion and at 3
month follow-up. Descriptive statistics, paired-samples t test, and content
analysis were used to analyze the data. FINDINGS: Work ability, fatigue, and
depression severity significantly improved postintervention. Participants
identified structure, work simulations, realism of simulated work environment,
support, and education as key intervention elements. IMPLICATIONS: Findings
underscore an occupationally focused return-to-work intervention for people
recovering from depression with potential for wider adoption and future research.
PMID- 29334792
TI - Mothers' opinions on being asked about exposure to intimate partner violence in
child healthcare centres in Sweden.
AB - Intimate partner violence (IPV) constitutes a hidden health risk for exposed
mothers and children. In Sweden, screening for IPV in healthcare has only been
routine during pregnancy, despite an increase in IPV following childbirth. The
arguments against routine questions postpartum have concerned a lack of evidence
of beneficial effects as well as fear of stigmatizing women or placing abused
women at further risk. Increased understanding of women's attitudes to routine
questions may allay these fears. In this study, 198 mothers in 12 child
healthcare centres (CHCs) filled in a short questionnaire about their exposure
and received information on IPV at a regular baby check-up visit. The mothers'
lifetime prevalence of exposure to IPV was 16%. One hundred and twenty-eight
mothers participated in a telephone interview, giving their opinion on the
screening experience. The intervention was well-received by most of the mothers
who reported that questions and information on IPV are essential for parents,
considering the health risks for children, and that the CHC is a natural arena
for this. Necessary prerequisites were that questioning be routine to avoid
stigmatizing and be offered in privacy without the partner being present.
PMID- 29334791
TI - Application of Fluorescence-Guided Surgery to Subsurface Cancers Requiring Wide
Local Excision: Literature Review and Novel Developments Toward Indirect
Visualization.
AB - The excision of tumors by wide local excision is challenging because the mass
must be removed entirely without ever viewing it directly. Positive margin rates
in sarcoma resection remain in the range of 20% to 35% and are associated with
increased recurrence and decreased survival. Fluorescence-guided surgery (FGS)
may improve surgical accuracy and has been utilized in other surgical
specialties. ABY-029, an anti-epidermal growth factor receptor Affibody molecule
covalently bound to the near-infrared fluorophore IRDye 800CW, is an excellent
candidate for future FGS applications in sarcoma resection; however, conventional
methods with direct surface tumor visualization are not immediately applicable. A
novel technique involving imaging through a margin of normal tissue is needed. We
review the past and present applications of FGS and present a novel concept of
indirect FGS for visualizing tumor through a margin of normal tissue and aiding
in excising the entire lesion as a single, complete mass with tumor-free margins.
PMID- 29334794
TI - A look at the progress of treating pancreatic cancer over the past 20 years.
AB - INTRODUCTION: Pancreatic cancer is known to be the deadliest of all common
cancers. Despite all efforts in pancreatic cancer treatment, the five-year
survival rates at diagnosis over the past 20 years have only increased from 5% to
8%. Assuming that pancreatic cancer is going to become the second most frequent
cause of cancer related death in the next 20 years, we are all encouraged to
treat patients in clinical trials to gain improvements in this devastating
disease. Areas covered: This review will provide a summary of pancreatic cancer
treatment over the last 20 years, starting with the pivotal study in 1997 which
showed the superiority of gemcitabine over 5-FU in advanced pancreatic cancer and
is marked as the beginning of a new era in pancreatic cancer treatment. This
review will also focus on improvements in different areas of treatment, including
pancreatic surgery, adjuvant treatment, neoadjuvant therapy and palliative
therapy. Expert commentary: The treatment of pancreatic cancer has changed
substantially in the last 20 years compared to almost no improvements in the
decades before. This provides hope that more effective treatment options will
become available in the near future. Particularly, new concepts such as
neoadjuvant therapy in resectable and borderline-resectable tumors may
potentially shift treatment strategies.
PMID- 29334793
TI - Controlled synthesis and size effects of multifunctional mesoporous silica
nanosystem for precise cancer therapy.
AB - Nanomaterials-based drug delivery systems display potent applications in cancer
therapy, owing to the enhanced permeability and retention effect and diversified
chemical modification. In this study, we have tailored and synthesized different
sized mesoporous silica nanoparticles (MSNs) through reactant control to
investigate the relevancy of nanoparticle size toward anticancer efficacy and
suppressing cancer multidrug resistance. The different sized MSNs loaded with
anticancer ruthenium complex (RuPOP) and conjugated with folate acid (FA) to
enhance the selectivity between cancer and normal cells. The nanosystem (Ru@MSNs)
can specifically recognize HepG2 hepatocellular carcinoma cells, thus enhance
accumulation and selective cellular uptake. The smaller sized (20 nm) Ru@MSNs
exhibit higher anticancer activity against HepG2 cells, while the larger sized
(80 nm) Ru@MSNs exhibit higher inhibitory effect against DOX-resistant
hepatocellular carcinoma cells (R-HepG2). Moreover, Ru@MSNs induced ROS
overproduction in cancer cells, leading to DNA damage and p53 phosphorylation,
consequently promoting cancer cells apoptosis. Ru@MSNs (80 nm) also inhibited
ABCB1 and ABCG2 expression in R-HepG2 cells to prevent drug efflux, thus overcome
multidrug resistance. Ru@MSNs also inhibited tumor growth in vivo without obvious
toxicity in major organs of tumor-bearing nude mice. Taken together, these
results verify the size effects of MSNs nanosystem for precise cancer therapy.
PMID- 29334795
TI - Progress in the development of histamine H3 receptor antagonists/inverse
agonists: a patent review (2013-2017).
AB - INTRODUCTION: Since years, ligands blocking histamine H3 receptor (H3R) activity
(antagonists/inverse agonists) are interesting targets in the search for new
cures for CNS disorders. Intensive works done by academic and pharmaceutical
company researchers have led to many potent and selective H3R antagonists/inverse
agonists. Some of them have reached to clinical trials. Areas covered: Patent
applications from January 2013 to September 2017 and the most important topics
connected with H3R field are analysed. Espacenet, Patentscope, Pubmed,
GoogleScholar or Cochrane Library online databases were principially used to
collect all the materials. Expert opinion: The research interest in histamine H3R
field is still high although the number of patent applications has decreased
during the past 4 years (around 20 publications). Complexity of histamine H3R
biology e.g. many isoforms, constitutive activity, heteromerization with other
receptors (dopamine D2, D1, adenosine A2A) and pharmacology make not easy
realization and evaluation of therapeutic potential of anti-H3R ligands. First
results from clinical trials have verified potential utility of histamine H3R
antagonist/inverse agonists in some diseases. However, more studies are necessary
for better understanding of an involvement of the histaminergic system in CNS
related disorders and helping more ligands approach to clinical trials and the
market. Lists of abbreviations: hAChEI - human acetylcholinesterase inhibitor;
hBuChEI - human butyrylcholinesterase inhibitor; hMAO - human monoamine oxidase;
MAO - monoamine oxidase.
PMID- 29334796
TI - The systematic review of randomized controlled trials of PCSK9 antibodies
challenges their "efficacy breakthrough" and the "lower, the better" theory.
AB - BACKGROUND: A Cochrane review with meta-analysis showed controversial results
about the efficacy of PCSK9 antibodies in the prevention of cardiovascular
diseases. This review gives the opportunity to test the relationship between LDL
C levels and cardiovascular events. METHODS: The authors analyzed the
relationship between the calculated LDL-C lowering and the risk of all-cause
mortality, fatal and non-fatal myocardial infarction, fatal and non-fatal stroke,
any adverse event, cardiovascular events and cardiovascular disease mortality.
RESULTS: No beneficial relationship was found between LDL-C lowering and
cardiovascular events explored by meta-regression; instead, there was a trend
toward harm. For any of the other outcomes there was no significant association
between LDL-C lowering and risk. Furthermore, the authors calculated the efficacy
that would be expected through the LDL-C lowering showed in the meta-analysis,
considering widely accepted predictions. These were respected only for stroke,
while the observed efficacy on other cardiovascular events was significantly
lower than the expected, and no significant result was observed at all for fatal
outcomes. A separate meta-analysis of trials recruiting familial
hypercholesterolemia patients have showed a tendency to harm for almost all
outcomes. CONCLUSIONS: The relationship between LDL-C lowering and cardiovascular
events has not showed any significant association (and even a tendency toward
harm), challenging the "lower the better" theory. A separate meta-analysis of
trials recruiting familial hypercholesterolemia patients has showed a tendency to
harm for all outcomes with PCSK9 antibodies. Therefore, at the moment, the data
available from randomized trials does not clearly support the use of these
antibodies.
PMID- 29334797
TI - Association of functional MMP-2 gene variant with intracranial aneurysms: case
control genetic association study and meta-analysis.
AB - INTRODUCTION: Abnormalities in Matrix Metalloproteinase (MMP) genes, which are
important in extracellular matrix (ECM) maintenance and therefore arterial wall
integrity are a plausible underlying mechanism of intracranial aneurysm (IA)
formation, growth and subsequent rupture. We investigated whether the rs243865 C
> T SNP (single nucleotide polymorphism) within the MMP-2 gene (which influences
gene transcription) is associated with IA compared to matched controls. MATERIALS
AND METHODS: We conducted a case-control genetic association study, adjusted for
known IA risk factors (smoking and hypertension), in a UK Caucasian population of
1409 patients with intracranial aneurysms (IA), and 1290 matched controls, to
determine the association of the rs243865 C > T functional MMP-2 gene SNP with IA
(overall, and classified as ruptured and unruptured). We also undertook a meta
analysis of two previous studies examining this SNP. RESULTS: The rs243865 T
allele was associated with IA presence in univariate (OR 1.18 [95% CI 1.04-1.33],
p = .01) and in multi-variable analyses adjusted for smoking and hypertension
status (OR 1.16 [95% CI 1.01-1.35], p = .042). Subgroup analysis demonstrated an
association of the rs243865 SNP with ruptured IA (OR 1.18 [95% CI 1.03-1.34] p =
.017), but, not unruptured IA (OR 1.17 [95% CI 0.97-1.42], p = .11). CONCLUSIONS:
Our study demonstrated an association between the functional MMP-2 rs243865
variant and IAs. Our findings suggest a genetic role for altered extracellular
matrix integrity in the pathogenesis of IA development and rupture.
PMID- 29334798
TI - Vulvar vestibular effects of ospemifene: a pilot study.
AB - The study aimed to assess the effects of ospemifene on vulvar vestibule in
postmenopausal women with vulvar pain and dyspareunia. Fifty-five postmenopausal
women used oral ospemifene 60 mg/d for 60 d. Symptoms of dryness, burning, and
dyspareunia were evaluated on a 10 cm visual analog scale. Visual examination of
the vulvar vestibule was also conducted. Patients also underwent current
perception threshold (CPT) testing obtained from the vulvar vestibule. Fifty-five
patients (94.6%) completed the treatment. Hot flashes were the most frequent
adverse effects, but this led to a discontinuation of therapy in three patients
(5.4%). After therapy, there was a statistically significant decrease from the
baseline in the mean scores for dryness, burning, and dyspareunia and reduction
of vestibular trophic score (baseline value of 11.2-4.2 after the therapy, p <=
002) and cotton swab test scores (2.81 compared with 1.25, p = .001). There was a
difference in CPT values for all nerve fibers and more consistent for C fibers (
38% of sensitivity). These results confirm the efficacy of ospemifene on
postmenopausal vestibular symptoms and signs; moreover, the drug was effective in
normalizing vestibular innervation sensitivity.
PMID- 29334799
TI - Potential of EPR spin-trapping to investigate in situ free radicals generation
from skin allergens in reconstructed human epidermis: cumene hydroperoxide as
proof of concept.
AB - The first step in the development of skin sensitisation to a chemical, and in the
elicitation of further allergic contact dermatitis (ACD), is the binding of the
allergen to skin proteins after penetrating into the epidermis. The so-formed
antigenic adduct is then recognised by the immune system as foreign to the body.
Sensitising organic hydroperoxides derived from autoxidation of natural terpenes
are believed to form antigens through radical-mediated mechanisms, although this
has not yet been established. So far, in vitro investigations on reactive radical
intermediates derived from these skin sensitisers have been conducted in
solution, yet with experimental conditions being far away from real-life
sensitisation. Herein, we report for the first time, the potential use of EPR
spin-trapping to study the in situ generation of free radicals derived from
cumene hydroperoxide CumOOH in a 3D reconstructed human epidermis (RHE) model,
thus much closer to what may happen in vivo. Among the undesirable effects
associated with dermal exposure to CumOOH, it is described to cause allergic and
irritant dermatitis, being reported as a significant sensitiser. We considered
exploiting the usage of spin-trap DEPMPO as an extensive view of all sort of
radicals derived from CumOOH were observed all at once in solution. We showed
that in the EpiskinTM RHE model, both by incubating in the assay medium and by
topical application, carbon radicals are mainly formed by redox reactions
suggesting the key role of CumOOH-derived carbon radicals in the antigen
formation process.
PMID- 29334801
TI - Bu-Shen-Yi-Qi formula impairs cytotoxicity of NK cells by up-regulating IDO
expression in trophoblasts.
AB - Recurrent spontaneous abortion (RSA) is a common health problem that affects
about 5% of fertile women, when it occurs for unknown reasons, it is called
unexplained recurrent spontaneous abortion (URSA). Traditional Chinese medicine,
such as Bu-Shen-Yi-Qi formula which consists of Dangshen, Tusizi, Baizhu,
Baishuo, Duzhong, Sangjisheng, Sugeng, and Tiaohuangqin, has played an invaluable
role in the treatment of RSA since ancient times. However, the mechanism of how
it takes effect is still not clear. To identify Bu-Shen-Yi-Qi formula could
modulate immune condition at maternal-fetal interface via its effect on
trophoblasts, HTR-8 of different treatment were co-cultured with peripheral or
decidual natural killer (NK) cells, and the receptors such as NKP30 and NKP46
expression on NK cells were measured by flow cytometry (FCM). In this study, we
found that herb medium could increase the IDO expression at appropriate
concentrations. As an inhibitor of IDO, 1-MT could impair the inhibitory function
of trophoblasts on NK cells. Furthermore, Bu-Shen-Yi-Qi formula could enhance the
inhibitory function of trophoblasts on NK cells. In conclusion, Bu-Shen-Yi-Qi
formula can inhibit NK cytotoxicity by up-regulating IDO expression in
trophoblasts and play a role in the treatment of URSA patients.
PMID- 29334802
TI - Youth and young adults with acquired brain injury transition towards work-related
roles: a qualitative study.
AB - PURPOSE: The purpose of this research was to explore the experiences of youth and
young adults with acquired brain injury as they transition towards work-related
roles. Little is known about employment experiences among this age group.
Understanding their perspectives can inform programs and clinical practice.
MATERIALS AND METHODS: A descriptive qualitative design, including semi
structured interviews with 14 participants (8 females; 6 males) was used.
Interviews were transcribed verbatim and analyzed using an open-coding, thematic
approach. RESULTS: Three major themes emerged related to the experience of work
related roles: (1) getting to know the new me; (2) navigating support systems;
and (3) taking control of my experience. Some participants used coping strategies
to acquire and/or maintain work-related roles, while others felt limited by their
condition. CONCLUSIONS: A variety of work-related roles, people, and environments
directly and indirectly influenced the work-related transition of youth and young
adults with acquired brain injury. Individuals expressed the importance of
acquired brain injury awareness in informing others about their impairments. In
fact, a lack of acquired brain injury awareness was often a main reason for
receiving less than adequate support and accommodations. Without an understanding
of acquired brain injury, people in the lives of these individuals were unable to
perceive the legitimacy of acquired brain injury-related impairments.
Implications for rehabilitation The purpose of this study is to understand the
experiences of youth and young adults with acquired brain injury as they
transition into work-related roles. Using these experiences as a guideline can
promote acquired brain injury awareness, and contribute to how current
interventions are designed and delivered. Clinicians should ensure that youth and
young adults with acquired brain injury have access to the resources they need to
maximize their independence. Healthcare professionals can play a pivotal role in
relaying important acquired brain injury-related education, implementing suitable
treatment plans, and providing them with effective tips to help them through
their transition. A healthy transition to work-related roles should include ample
social support and communication, acquired brain injury-related information that
informs the community of acquired brain injury impairments, needs, and recovery
trajectory, as well as adequate and consistent coordination within and between
the person and the environment.
PMID- 29334800
TI - Research progress of self-assembled nanogel and hybrid hydrogel systems based on
pullulan derivatives.
AB - Polymer nano-sized hydrogels (nanogels) as drug delivery carriers have been
investigated over the last few decades. Pullulan, a nontoxic and nonimmunogenic
hydrophilic polysaccharide derived from fermentation of black yeast like
Aureobasidium pullulans with great biocompatibility and biodegradability, is one
of the most attractive carriers for drug delivery systems. In this review, we
describe the preparation, characterization, and 'switch-on/off' mechanism of
typical pullulan self-assembled nanogels (self-nanogels), and then introduce the
development of hybrid hydrogels that are numerous resources applied for
regenerative medicine. A major section is used for biomedical applications of
different nanogel systems based on modified pullulan, which exert smart stimuli
responses at ambient conditions such as charge, pH, temperature, light, and
redox. Pullulan self-nanogels have found increasingly extensive application in
protein delivery, tissue engineering, vaccine development, cancer therapy, and
biological imaging. Functional groups are incorporated into self-nanogels and
contribute to expressing desirable results such as targeting and modified
release. Various molecules, especially insoluble or unstable drugs and
encapsulated proteins, present improved solubility and bioavailability as well as
reduced side effects when incorporated into self-nanogels. Finally, the
advantages and disadvantages of pullulan self-nanogels will be analyzed
accordingly, and the development of pullulan nanogel systems will be reviewed.
PMID- 29334803
TI - In vitro fermentation of gum acacia - impact on the faecal microbiota.
AB - Interest in the consumption of gum acacia (GA) has been associated with
beneficial health effects, which may be mediated in part by prebiotic activity.
Two doses of GA and fructooligosaccharide (FOS) (1 and 2%) were tested for their
efficacy over 48 h in pH- and temperature-controlled anaerobic batch cultures
inoculated with human faeces. Samples were taken after 0, 5, 10, 24 and 48 h of
fermentation. The selective effects of GA (increases in Bifidobacterium spp. and
Lactobacillus spp.) were similar to those of the known prebiotic FOS. The 1% dose
of substrates showed more enhanced selectivity compared to the 2% dose. The
fermentation of GA also led to SCFA production, specifically increased acetate
after 10, 24 and 48 h of fermentation, propionate after 48 h and butyrate after
24 and 48 h. In addition, FOS led to significant increase in the main SCFAs.
These results suggest that GA displays potential prebiotic properties.
PMID- 29334804
TI - Characterizing on-road driving performance in individuals with traumatic brain
injury who pass or fail an on-road driving assessment.
AB - OBJECTIVE: To characterise on-road driving performance in individuals with
traumatic brain injury who fail on-road driving assessment, compared with both
those who pass assessment and healthy controls, and the injury and cognitive
factors associated with driving performance. STUDY DESIGN: Cross-sectional.
METHODS: Forty eight participants with traumatic brain injury (Age M = 40.50 SD =
14.62, 77% male, post-traumatic amnesia days M = 28.74 SD =27.68) and 48 healthy
matched controls completed a standardised on-road driving assessment in addition
to cognitive measures. RESULTS: Individuals with traumatic brain injury who
passed on-road driving assessment performed no differently from controls while
individuals with traumatic brain injury who failed the assessment demonstrated
significantly worse driving performance relative to controls across a range of
driving manoeuvres and error types including observation of on-road environment,
speed control, gap selection, lane position, following distance and basic car
control. Longer time post-injury and reduced visual perception were both
significantly correlated with reduced driving skills. CONCLUSIONS: This
exploratory study indicated that drivers with traumatic brain injury who failed
on-road assessment demonstrated a heterogeneous pattern of impaired driving
manoeuvres, characterised by skill deficits across both operational (e.g., basic
car control and lane position) and tactical domains (e.g., following distance,
gap selection, and observation) of driving. These preliminary findings can be
used for implementation of future driving assessments and rehabilitation
programs. Implications for rehabilitation Clinicians should be aware that the
majority of individuals with traumatic brain injury were deemed fit to resume
driving following formal on-road assessment, despite having moderate to very
severe traumatic brain injuries. Drivers with traumatic brain injury who failed
an on-road assessment demonstrated a heterogeneous pattern of impaired skills
including errors with observation, speed regulation, gap selection, and vehicle
control and accordingly had difficulty executing a diverse range of common
driving manoeuvres. Comprehensive, formal on-road assessments, incorporating a
range of skills, and manoeuvres, are needed to evaluate readiness to return to
driving following traumatic brain injury. Individually tailored driver
rehabilitation programs need to address these heterogeneous skill deficits to
best support individuals to make a successful return to driving post-traumatic
brain injury.
PMID- 29334806
TI - Effect of scuba diving on the oxidant/antioxidant status, SIRT1 and SIRT3
expression in recreational divers after a winter nondive period.
AB - The aim of this study was to examine the effects of scuba diving on oxidative
damage markers in erythrocytes and plasma, antioxidant system in peripheral blood
mononuclear cells (PBMCs), as well as sirtuin 1 (SIRT1) and sirtuin 3 (SIRT3)
gene expressions in recreational divers after a winter nondive period (at least 5
months). For that purpose, 17 male recreational divers performed an immersion at
a depth of 30 m for 30 min. Blood samples were collected immediately before and
after diving, 3 and 6 h after diving. Erythrocyte lipid peroxidation measured by
thiobarbituric-reactive substances (TBARS) method was significantly increased
immediately after diving, but returned to the baseline 6 h after diving, while no
significant change was found for plasma TBARS and protein carbonyl derivates in
both plasma and erythrocytes. Diving-induced catalase (CAT), superoxide dismutase
2 (SOD2), and consequently total superoxide dismutase (SOD) activities in the
PBMC samples (significantly increased immediately after diving, reached the
maximum activities 3 h after diving, while 6 h after diving only CAT activity
remained significantly increased). No significant change was observed for SOD1
activity and gene expression, as well as SOD2 expression, while CAT and SIRT1
expressions were slightly decreased immediately after diving and 3 h after
diving. Interestingly, SIRT3 expression was significantly increased 6 h after
diving. In conclusion, after the first dive to 30 m after a nondive season,
activation of antioxidant defence was not sufficient to prevent oxidative damage,
while SIRT3 upregulation could be a step towards an adaptive response to the
diving.
PMID- 29334807
TI - Methodologies for the airbrush application of MALDI matrices.
AB - There is still a need to develop reliable and robust matrix deposition methods
for matrix-assisted laser desorption/ionisation mass spectrometry that are
applicable to a range of matrices, solvents and analyte types. This paper
presents a robust methodology for the airbrush application of matrices along with
the implications of varying the set-up and airbrush parameters. A small number of
organic analytes and metal salts are analysed in both positive and negative ion
modes to exemplify this methodology. In the analyses with the airbrush deposited
matrices, performance was enhanced when compared to standard pipette deposition
with the need for a search for sweat spots greatly diminished due to the increase
homogeneity of the matrix surface and resultant analyte spots. As expected, the
graphite matrices were shown to specifically outperform the organic matrices in
negative ion mode.
PMID- 29334805
TI - Delivery of radix ophiopogonis polysaccharide via sucrose acetateisobutyrate
based in situ forming systems alone or combined with itsmono-PEGylation.
AB - This work aimed to achieve long-lasting delivery of radix ophiopogonis
polysaccharide (ROP) by sucrose acetate isobutyrate (SAIB)-based in situ forming
systems (ISFSs) alone or combined with mono-PEGylation of ROP. When the
'90%SAIB/10% solvent' system was used, the mean residence time (MRT) of ROP was
prolonged by 4.3 5 ~ 7.00 times and the initial release rate was reduced
significantly. However, this system was only suitable for days-long sustained
release of ROP in short-term therapy. As to the 'SAIB/additives/solvent' system
containing mono-PEGylated ROP, the results indicated that SAIB/poly(d,l-lactide
co-glycolide) (PLGA)/N-methyl-2-pyrrolidone (NMP) was superior to SAIB/polylactic
acid (PLA)/NMP and SAIB/PLA/ethanol in controlled release. Moreover, weeks- to
months-long (16-60 d) smooth release of ROP could be achieved by varying the
concentration (10-30%) and molecular weight (MW) of PLGA (10-50 kDa) or by
employing a moderate MW of PEGylated ROP (~20 or ~30 kDa). With further
increasing the conjugate MW to ~40 kDa, the contribution of drug elimination to
its plasma retention seemed to surpass that of the SAIB-based system, resulting
in that the system no longer had an obvious influence on the in vivo behavior of
the conjugate. Besides, the results of host response confirmed that with less
solvent being used, the SAIB-based systems showed a higher biocompatibility than
the PLGA-based systems, suggesting that they could be freely chosen in the
prevention and/or cure of chronic diseases.
PMID- 29334808
TI - Identification of a novel site of interaction between ataxin-3 and the amyloid
aggregation inhibitor polyglutamine binding peptide 1.
AB - Amyloid diseases represent a growing social and economic burden in the developed
world. Understanding the assembly pathway and the inhibition of amyloid formation
is key to developing therapies to treat these diseases. The neurodegenerative
condition Machado-Joseph disease is characterised by the self-aggregation of the
protein ataxin-3. Ataxin-3 consists of a globular N-terminal Josephin domain,
which can aggregate into curvilinear protofibrils, and an unstructured,
dynamically disordered C-terminal domain containing three ubiquitin interacting
motifs separated by a polyglutamine stretch. Upon expansion of the polyglutamine
region above 50 residues, ataxin-3 undergoes a second stage of aggregation in
which long, straight amyloid fibrils form. A peptide inhibitor of polyglutamine
aggregation, known as polyQ binding peptide 1, has been shown previously to
prevent the maturation of ataxin-3 fibrils. However, the mechanism of this
inhibition remains unclear. Using nanoelectrospray ionisation-mass spectrometry,
we demonstrate that polyQ binding peptide 1 binds to monomeric ataxin-3. By
investigating the ability of polyQ binding peptide 1 to bind to truncated ataxin
3 constructs lacking one or more domains, we localise the site of this
interaction to a 39-residue sequence immediately C-terminal to the Josephin
domain. The results suggest a new mechanism for the inhibition of polyglutamine
aggregation by polyQ binding peptide 1 in which binding to a region outside of
the polyglutamine tract can prevent fibril formation, highlighting the importance
of polyglutamine flanking regions in controlling aggregation and disease.
PMID- 29334809
TI - Accidental pharmacological poisonings in young children: population-based study
in three settings.
AB - INTRODUCTION: Pharmacological poisonings in young children are avoidable.
Previous studies report calls to poisons centres, presentations to emergency
departments (ED) or hospital admissions. There are limited data assessing
concurrent management of poisonings across all three settings. We aimed to
describe accidental pharmacological poisonings in young children across our
Poisons Information Centre (PIC), EDs and hospitals. METHODS: A population-based
study in New South Wales, Australia, of PIC calls, ED presentations and hospital
admissions for accidental pharmacological poisoning in children aged <5 years,
2007-2013. We examined trends, medicines responsible and subsequent management.
Medicines were coded using ICD10-AM diagnosis codes (T36-50). RESULTS: Over 2007
2013, pharmacological poisonings accounted for 67,816 PIC calls, 7739 ED
presentations and 2082 admissions. Rates (per 10,000 children) of PIC calls
declined from 220 to 178; ED presentations were stable (~22-24), with a decrease
in emergency cases offset by an increase in semi- or non-urgent presentations;
hospital admissions declined (8-5). Most PIC calls related to "non-opioid
analgesics" (25%), and "topical agents" (18%). Nearly every day, one child aged
<5 years was admitted to hospital for poisoning. "Benzodiazepines", "other and
unspecified antidepressants", "uncategorised antihypertensives", and "4
aminophenol derivatives" accounted for over one-third of all admissions. Most PIC
calls (90%) were advised to stay home, 6% referred to hospital. One-quarter of ED
presentations resulted in admission. CONCLUSIONS: Poisonings reported to PIC and
hospitals declined, however, non-urgent ED presentations increased. Strategies to
reduce therapeutic errors and access to medicines, and education campaigns to
improve Poisons Centre call rates to prevent unnecessary ED presentations are
needed.
PMID- 29334810
TI - Monitoring of Metabolic Adverse Effects Associated With Atypical Antipsychotics
Use in an Outpatient Psychiatric Clinic.
AB - BACKGROUND: Atypical antipsychotics are associated with metabolic complications
that contribute to a higher risk of cardiovascular disease. Current evidence
reveal suboptimal adherence to the complex and variable official recommendations
on metabolic monitoring in the corresponding patient population. A study
evaluating metabolic monitoring at guideline-recommended intervals may help
identify areas for intervention. OBJECTIVE: Describe the frequency of monitoring
metabolic adverse effects in patients receiving atypical antipsychotics in an
outpatient psychiatric clinic with respect to the specific guideline-recommended
intervals. METHODS: A retrospective chart review was conducted in the outpatient
psychiatric clinic. The primary outcome measure was the percentage of patients
monitored for metabolic parameters at the current guideline-recommended
intervals. The secondary end points were the percentage of patients with
documented primary care physician, untreated metabolic comorbidities, and treated
metabolic comorbidities by disease state. RESULTS: The most assessed parameters
were family history (98%), blood pressure (81%), and body mass index/body weight
(83%) at the baseline interval. The least assessed parameters were lipids (14%)
at the 12-week interval and waist circumference (0%) at any interval. CONCLUSION:
Interventions are needed to encourage higher compliance with current
recommendations. The complexity of the recommendations is the most likely reason
for the suboptimal compliance.
PMID- 29334811
TI - The experiences of physical rehabilitation in individuals with spinal cord
injuries: a qualitative thematic synthesis.
AB - PURPOSE: The purpose of this thematic synthesis review was to identify and
synthesise published qualitative research on the perspectives of individuals with
spinal cord injuries with respect to physical rehabilitation interventions.
MATERIALS AND METHODS: The peer-reviewed literature was searched across seven
databases and identified abstracts were independently screened by two reviewers.
A thematic synthesis methodology was used to code and synthesise the results from
the included studies. RESULTS: In total, 7233 abstracts were identified; 31
articles were selected for inclusion, representing 26 physical rehabilitation
interventions. The methodological quality of studies was moderate (Standards for
Reporting Qualitative Research mean +/- standard deviation = 14.39 +/- 3.61). The
four main themes developed were: (1) Benefits of physical rehabilitation, (2)
Challenges of physical rehabilitation, (3) Need for support, and (4) Issue of
control. CONCLUSIONS: This qualitative thematic synthesis provides key insights
into the experiences of individuals with spinal cord injuries who received
physical rehabilitation. Recommendations for practice, based on the findings,
include creating a diverse, encouraging, and educational physical rehabilitation
experience with supportive staff who focus on communication and person-centred
care. Implications for Rehabilitation Physical rehabilitation provides
psychological as well as physical benefits to people with spinal cord injuries,
including motivation, hope, improved self-confidence, and acceptance. Challenges
identified during physical rehabilitation for people with spinal cord injuries,
such as comparisons, negative emotions, recovery expectations, and slow progress,
should be addressed by healthcare professionals to ensure person-centred care.
People with spinal cord injuries identified a need for support from health care
professionals, family, and friends, as well other people with spinal cord
injuries. There is an issue of control in physical rehabilitation for people with
spinal cord injuries, which can result in a fight with oneself or with healthcare
professionals to regain the control that has been lost.
PMID- 29334812
TI - Anti-biofilm effect of a butenolide/polymer coating and metatranscriptomic
analyses.
AB - Butenolide is an environmentally friendly antifouling natural product, but its
efficiency and mechanism in preventing biofilm formation have not been examined.
Furthermore, controlling the release of butenolide from paints into seawater is
technically challenging. A coating was developed by mixing butenolide with a
biodegradable polymer, poly (epsilon-caprolactone)-based polyurethane, and a one
month in situ anti-biofilm test was conducted in a subtidal area. The constant
release of butenolide from the surface suggested that its release was well
controlled. Direct observation and confocal microscope investigation indicated
that the coating was effective against both biofilm formation and attachment of
large fouling organisms. Metatranscriptomic analysis of biofilm samples implied
that the coating selectively inhibited the adhesion of microbes from a variety of
phyla and targeted particular functional pathways including energy metabolism,
drug transport and toxin release. These integrated analyses demonstrated the
potential application of this butenolide/polymer coating as an anti-biofilm
material.
PMID- 29334813
TI - Reduction of bacterial adhesion on titanium-doped diamond-like carbon coatings.
AB - A range of titanium doped diamond-like carbon (Ti-DLC) coatings with different Ti
contents were prepared on stainless steel substrates using a plasma-enhanced
chemical vapour deposition technique. It was found that both the electron donor
surface energy and the surface roughness of the Ti-DLC coatings increased with
increasing Ti contents in the coatings. Bacterial adhesion to the coatings was
evaluated against Escherichia coli WT F1693 and Pseudomonas aeruginosa ATCC
33347. The experimental data showed that bacterial adhesion decreased with the
increases of the Ti content, the electron donor surface energy and surface
roughness of the coatings, while the bacterial removal percentage increased with
the increases of these parameters. The Ti-DLC coatings reduced bacterial
attachment by up to 75% and increased bacterial detachment from 15 to 45%,
compared with stainless steel control.
PMID- 29334815
TI - Impact of medication adherence on risk of ischemic stroke, major bleeding and
deep vein thrombosis in atrial fibrillation patients using novel oral
anticoagulants.
AB - OBJECTIVES: Our study examined the impact of adherence to novel oral
anticoagulants [NOACs - dabigatran and rivaroxaban] on ischemic-stroke (IS),
major-bleeding (MB), deep-vein-thrombosis and pulmonary-embolism (DVTPE) risk in
a large, nationwide, propensity-matched sample. METHODS: A retrospective cohort
study utilized data from a US commercial managed-care database (2010-2012). Adult
patients with >=1 diagnosis of atrial fibrillation/flutter (ICD-9 427.31/32), >1
prescription of NOACs and CHA2DS2-VASc score >=1 were included. Patients were
categorized as adherent versus nonadherent (using proportion of days covered [PDC
>=80%]) based on their NOAC use up to 6 months and those continued its use up to
12 months. The patients were matched using propensity score (based on inverse
probability treatment weighting) and the risk of IS, MB, DVTPE outcomes was
evaluated for the matched cohorts' post-adherence (exposure) assessment using
multivariable Cox regression. RESULTS: A total of 3,629 and 1,946 patients with
at least 6 and 12 months of NOAC use were included. Based on a PDC threshold of
>=80%, adherence rates at 6 and 12 month usage were 77% and 76%, respectively.
Patients with lowest adherence were from the South, had low stroke risk and
EPO/HMO insurance. Using Cox models with matched cohorts, nonadherence within the
first 6 months' use was significantly associated with higher risk of IS and DVTPE
(IS: hazard ratio [HR] = 1.82, p = .002; DVTPE: HR = 2.12, p = .010) and the risk
increased with nonadherence for the prolonged period of 12 months' use (IS: HR =
2.08, p = .022; DVTPE: HR = 5.39, p = .003). The risk of MB was not different (p
> .05) between adherent and nonadherent groups for both 6 month and 12 month
cohorts. CONCLUSION: Adherence to NOACs for both 6 months and prolonged use (up
to 12 months) was associated with a reduction in IS and DVTPE risk, but did not
substantially increase risk of MB. Further studies on newer, individual NOACs and
older populations are warranted.
PMID- 29334814
TI - Dual-ligand modified liposomes provide effective local targeted delivery of lung
cancer drug by antibody and tumor lineage-homing cell-penetrating peptide.
AB - The abilities of a drug delivery system to target and penetrate tumor masses are
key factors in determining the system's chemotherapeutic efficacy. Here, we
explored the utility of an anti-carbonic anhydrase IX (anti-CA IX) antibody and
CPP33 dual-ligand modified triptolide-loaded liposomes (dl-TPL-lip) to
simultaneously enhance the tumor-specific targeting and increase tumor cell
penetration of TPL. In vitro, the dl-TPL-lip increased the cytotoxicity of TPL in
CA IX-positive lung cancer cells, which showed tunable size (137.6 +/- 0.8 nm),
high-encapsulation efficiency (86.3 +/- 2.6%) and sustained release. Dl-TPL-lip
significantly improved the ability of liposomes to penetrate 3 D tumor spheroids
and exhibited a superior inhibiting effect. Furthermore, pharmacokinetic studies
in rats that received TPL liposomal formulations by endotracheal administration
showed a reduced concentration of TPL (17.3%-30.6% compared to free TPL) in
systemic circulation. After pulmonary administration in orthotopic lung tumor
bearing mice, dl-TPL-lip significantly enhanced TPL anti-cancer efficacy without
apparent systemic toxicity. This dual-ligand modified liposomal vehicle presents
a potential system for localized and targeted delivery of anti-cancer drugs to
improve their efficacy.
PMID- 29334816
TI - Anti-colchicine Fab fragments prevent lethal colchicine toxicity in a porcine
model: a pharmacokinetic and clinical study.
AB - BACKGROUND: Colchicine poisoning is commonly lethal. Colchicine-specific Fab
fragments increase rat urinary colchicine clearance and have been associated with
a good outcome in one patient. We aimed to develop a porcine model of colchicine
toxicity to study the pharmacokinetics and efficacy of ovine Fab. METHODS: A
Gottingen minipig critical care model was established and serial blood samples
taken for colchicine and Fab pharmacokinetics, clinical chemistry, and
haematology. Animals were euthanised when the mean arterial pressure fell below
45 mmHg without response to vasopressor, or at study completion. RESULTS: Initial
studies indicated that oral dosing produced variable pharmacokinetics and time-to
euthanasia. By contrast, intravenous infusion of 0.25 mg/kg colchicine over 1 h
produced reproducible pharmacokinetics (AUC0-20 343 [SD = 21] ug/L/h), acute
multi-organ injury, and cardiotoxicity requiring euthanasia a mean of 22.5 (SD =
3.2) h after dosing. A full-neutralising equimolar Fab dose given 6 h after the
infusion (50% first hour, 50% next 6 h [to reduce renal-loss of unbound Fab])
produced a 7.35-fold increase in plasma colchicine (AUC0-20 2,522 [SD = 14]
ug/L/h), and removed all free plasma colchicine, but did not prevent toxicity
(euthanasia at 29.1 [SD = 3.4] h). Earlier administration over 1 h of the full
neutralising dose, 1 or 3 h after the colchicine, produced a 12.9-fold (AUC0-20
4,433 [SD = 607] ug/L/h) and 6.0-fold (AUC0-20 2,047 [SD = 51] ug/L/h) increase
in plasma colchicine, respectively, absence of free plasma colchicine until 20 h,
and survival to study end without marked cardiotoxicity. CONCLUSIONS: Colchicine
specific Fab given early, in equimolar dose, bound colchicine, eliciting its
movement into the blood, and preventing severe toxicity. Clinical studies are now
needed to determine how soon this antidote must be given to work in human
poisoning.
PMID- 29334817
TI - QuantiFERON-plus does not discriminate between active and latent tuberculosis.
PMID- 29334818
TI - Relationship between nurses' moral sensitivity and the quality of care.
AB - BACKGROUND: To provide care with high quality, nurses face a number of moral
issues requiring them to have moral abilities in professional performance. Moral
sensitivity is the first step in moral performance. However, its relation to the
quality of care patients receive is controversial. RESEARCH OBJECTIVE: This study
aims to determine the relationship between the moral sensitivity of nurses and
the quality of care received by patients in the medical wards. RESEARCH DESIGN: A
descriptive correlational study using validated tools, including Moral
Sensitivity Questionnaire and the Quality Patient Quality Scale. Participants and
research context: In total, 198 nurses and 198 patients in 17 medical wards of
hospitals affiliated with Tabriz University of Medical Sciences, Iran. Ethical
considerations: The study was reviewed and approved by the Ethics Committee of
Tabriz University of Medical Sciences. FINDINGS: The mean values of nurses' moral
sensitivity and nurses' quality care were 136.47 +/- 13.30 and 196.36 +/- 44.10,
respectively. There was no significant relationship between the patient care
quality and nurses' moral sensitivity ( r = -.14, p = .5). However, there was a
significant inverse relationship between the dimension of "Experiencing moral
conflicts" and the overall score of quality care ( r = -.50, p = .04), the
dimensions of "psychosocial ( r = -.50, p = .04)" and "physical ( r = -.50, p =
.03)." CONCLUSION: Considering the significant inverse relationship between the
score of patient quality care and the dimension of moral conflict experience, it
seems when nurses make moral decisions, they experience a conflict between
personal and professional values in their careers and thus experience moral
tension. If this tension is not resolved properly, it can provide a way for them
to distance themselves from patients, thereby making nurses indifferent to moral
care.
PMID- 29334819
TI - Management of Hodgkin lymphoma in the era of brentuximab vedotin: real-world data
from five European countries.
AB - We examined real-world data on management of relapsed/refractory Hodgkin lymphoma
(R/R HL) in five European countries and the consistency of these data with
guideline recommendations. Retrospective clinical and epidemiologic data for 509
patients with R/R HL treated between January 2014 and March 2015 were collected
at centers in France, Germany, Italy, Spain, and the United Kingdom. Mean age was
46.3 years; 73.3% were receiving second-line therapy for a first relapse during
the reporting period. Most patients received ABVD as front-line chemotherapy,
except in Germany where escalated BEACOPP was used more often. The proportion of
patients receiving stem cell transplantation (SCT) was 44%; 85% of transplants
occurred at first relapse. Brentuximab vedotin (BV) was usually administered
after autologous SCT, and was initiated for 65% of patients following SCT
failure. Our findings suggest that R/R HL management across these countries is
broadly consistent with guideline recommendations and that BV is well-integrated
into treatment pathways.
PMID- 29334820
TI - EMT does not work regular shifts.
PMID- 29334821
TI - Development and validation of a facial expression database based on the
dimensional and categorical model of emotions.
AB - The present study describes the development and validation of a facial expression
database comprising five different horizontal face angles in dynamic and static
presentations. The database includes twelve expression types portrayed by eight
Japanese models. This database was inspired by the dimensional and categorical
model of emotions: surprise, fear, sadness, anger with open mouth, anger with
closed mouth, disgust with open mouth, disgust with closed mouth, excitement,
happiness, relaxation, sleepiness, and neutral (static only). The expressions
were validated using emotion classification and Affect Grid rating tasks
[Russell, Weiss, & Mendelsohn, 1989. Affect Grid: A single-item scale of pleasure
and arousal. Journal of Personality and Social Psychology, 57(3), 493-502]. The
results indicate that most of the expressions were recognised as the intended
emotions and could systematically represent affective valence and arousal.
Furthermore, face angle and facial motion information influenced emotion
classification and valence and arousal ratings. Our database will be available
online at the following URL. https://www.dh.aist.go.jp/database/face2017/ .
PMID- 29334822
TI - Vibsanol A induces differentiation of acute myeloid leukemia cells via activation
of the PKC signaling pathway and induction of ROS.
AB - Identifying novel differentiating agents to promote leukemia-cell differentiation
is a pressing need. Here, we demonstrated that vibsanol A, a vibsane-type
diterpenoid, inhibited the growth of acute myeloid leukemia (AML) cells via
induction of cell differentiation, which was characterized by G1 cell cycle
arrest. The differentiation-inducing effects of vibsanol A were dependent upon
protein kinase C (PKC) activation, and subsequent activation of the extracellular
signal-regulated kinase (ERK) pathway. Furthermore, vibsanol A treatment
increased reactive oxygen species (ROS) levels, and the ROS scavenger NAC
reversed the vibsanol A-induced cell differentiation, indicating an important
role for ROS in the action of vibsanol A. Finally, vibsanol A exhibited a
differentiation-enhancing effect when used in combination with all-trans retinoic
acid in AML cells. Overall results suggested that vibsanol A induces AML cell
differentiation via activation of the PKC/ERK signaling and induction of ROS.
Vibsanol A may prove to be an effective differentiating agent against AML.
PMID- 29334823
TI - A New Genus of Tapeworm (Cestoda: Onchoproteocephalidea) from Sawfish
(Elasmobranchii: Pristidae).
AB - Collections from the dwarf sawfish, Pristis clavata, near Darwin, Australia, in
1997 led to the discovery of the new onchoproteocephalidean genus Matticestus n.
gen.-a taxon that has been referred to in molecular phylogenetic analyses in
which it has been included as "New genus 8." Its type species, Matticestus anneae
n. gen., n. sp., and a second species, Matticestus kathleenae n. sp., are
described. Placement of this taxon in the Onchoproteocephalidea is supported
morphologically in that both species bear a scolex with 4 bothridia each with a
pair of bi-pronged hooks and spinitriches that extend throughout the length of
the body. Sequence data for the D1-D3 region of the 28S rDNA gene also place the
genus solidly among the other elasmobranch-hosted members of the order. The new
genus differs from the other elasmobranch-hosted genera in the order in that its
members possess a combination of biloculated bothridia with lateral lappets on
the posterior margin of the anterior loculus and a pair of bi-pronged hooks with
a distinctive configuration of tubercles and internal channels. Its members are
also extremely small. In summary, Matticestus n. gen. is an unusually tiny,
"spiny," genus of cestode that seems to exclusively parasitize sawfish of the
genus Pristis.
PMID- 29334824
TI - #MeToo - a concern for general practice?
PMID- 29334825
TI - The Influence of Traumatic Axonal Injury in Thalamus and Brainstem on Level of
Consciousness at Scene or Admission: A Clinical Magnetic Resonance Imaging Study.
AB - The aim of this study was to investigate how traumatic axonal injury (TAI)
lesions in the thalamus, basal ganglia, and brainstem on clinical brain magnetic
resonance imaging (MRI) are associated with level of consciousness in the acute
phase in patients with moderate to severe traumatic brain injury (TBI). There
were 158 patients with moderate to severe TBI (7-70 years) with early 1.5T MRI
(median 7 days, range 0-35) without mass lesion included prospectively. Glasgow
Coma Scale (GCS) scores were registered before intubation or at admission. The
TAI lesions were identified in T2*gradient echo, fluid attenuated inversion
recovery, and diffusion weighted imaging scans. In addition to registering TAI
lesions in hemispheric white matter and the corpus callosum, TAI lesions in the
thalamus, basal ganglia, and brainstem were classified as uni- or bilateral.
Twenty percent of patients had TAI lesions in the thalamus (7% bilateral), 18% in
basal ganglia (2% bilateral), and 29% in the brainstem (9% bilateral). One of 26
bilateral lesions in the thalamus or brainstem was found on computed tomography.
The GCS scores were lower in patients with bilateral lesions in the thalamus
(median four) and brainstem (median five) than in those with corresponding
unilateral lesions (median six and eight, p = 0.002 and 0.022). The TAI locations
most associated with low GCS scores in univariable ordinal regression analyses
were bilateral TAI lesions in the thalamus (odds ratio [OR] 35.8; confidence
interval [CI: 10.5-121.8], p < 0.001), followed by bilateral lesions in basal
ganglia (OR 13.1 [CI: 2.0-88.2], p = 0.008) and bilateral lesions in the
brainstem (OR 11.4 [CI: 4.0-32.2], p < 0.001). This Trondheim TBI study showed
that patients with bilateral TAI lesions in the thalamus, basal ganglia, or
brainstem had particularly low consciousness at admission. We suggest these
bilateral lesions should be evaluated further as possible biomarkers in a new TAI
MRI classification as a worst grade, because they could explain low consciousness
in patients without mass lesions.
PMID- 29334827
TI - Left Ventricular Pseudoaneurysms in Children-A Case Series.
AB - Left ventricular pseudoaneurysms are very rare in children. In children, left
ventricular pseudoaneurysms can occur following infection, trauma, ischemia, or
cardiac surgery. The authors report a series of three cases treated at our
hospital with two of the cases having a history of extrapulmonary tuberculosis
and one patient with a history of varicella zoster infection.
PMID- 29334826
TI - Patient safety culture in out-of-hours primary care services in the Netherlands:
a cross-sectional survey.
AB - OBJECTIVE: To examine patient safety culture in Dutch out-of-hours primary care
using the safety attitudes questionnaire (SAQ) which includes five factors:
teamwork climate, safety climate, job satisfaction, perceptions of management and
communication openness. DESIGN: Cross-sectional observational study using an
anonymous web-survey. Setting Sixteen out-of-hours general practitioner (GP)
cooperatives and two call centers in the Netherlands. Subjects Primary healthcare
providers in out-of-hours services. Main outcome measures Mean scores on patient
safety culture factors; association between patient safety culture and
profession, gender, age, and working experience. RESULTS: Overall response rate
was 43%. A total of 784 respondents were included; mainly GPs (N = 470) and
triage nurses (N = 189). The healthcare providers were most positive about
teamwork climate and job satisfaction, and less about communication openness and
safety climate. The largest variation between clinics was found on safety
climate; the lowest on teamwork climate. Triage nurses scored significantly
higher than GPs on each of the five patient safety factors. Older healthcare
providers scored significantly higher than younger on safety climate and
perceptions of management. More working experience was positively related to
higher teamwork climate and communication openness. Gender was not associated
with any of the patient safety factors. CONCLUSIONS: Our study showed that
healthcare providers perceive patient safety culture in Dutch GP cooperatives
positively, but there are differences related to the respondents' profession, age
and working experience. Recommendations for future studies are to examine reasons
for these differences, to examine the effects of interventions to improve safety
culture and to make international comparisons of safety culture. Key Points
Creating a positive patient safety culture is assumed to be a prerequisite for
quality and safety. We found that: * healthcare providers in Dutch GP
cooperatives perceive patient safety culture positively; * triage nurses scored
higher than GPs, and older and more experienced healthcare professionals scored
higher than younger and less experienced professionals - on several patient
safety culture factors; and * within the GP cooperatives, safety climate and
openness of communication had the largest potential for improvement.
PMID- 29334828
TI - An Unusual Combination of Double Inlet Left Ventricle With Discordant
Ventriculoarterial Connections and Bilateral Arterial Ducts.
AB - The presence of bilaterally persistent arterial ducts is an uncommon abnormality.
Here, we describe the anatomy and successful management of an unusual patient
with bilateral ducts in the setting of double inlet left ventricle, discordant
ventriculoarterial connections, aortic atresia, and a severely hypoplastic and
serpentine aortic arch.
PMID- 29334829
TI - Rare Combination of Pathologies Causing Mitral Stenosis and Mitral Regurgitation:
A Case Report.
AB - A supramitral ring is a rare cause of mitral stenosis, while an isolated mitral
valve cleft is a rare cause of congenital mitral regurgitation. Fortunately, both
the lesions are known to have good outcomes after surgical correction. Although
each is known to be associated with a variety of other structural heart defects,
their coexistence has not been reported previously. We report a case of a three-
and half-year-old boy detected to have a rare combination of supramitral ring
producing severe mitral stenosis with a coexisting cleft in the anterior leaflet
of mitral valve causing severe mitral regurgitation. The patient underwent
successful surgical repair with resolution of both mitral stenosis and
regurgitation.
PMID- 29334830
TI - Cardiopulmonary Bypass for a Patient With Congenital Hyperinsulinemia.
AB - Congenital hyperinsulinism is a clinical syndrome of pancreatic beta-cell
dysfunction characterized by failure to suppress insulin secretion in the
presence of hypoglycemia. Here, we describe the concerns, the techniques used to
ameliorate these potential problems, and the outcomes for a child with this
condition undergoing cardiopulmonary bypass for correction of an atrial septal
defect.
PMID- 29334831
TI - Does Stroke Rehabilitation Really Matter? Part B: An Algorithm for Prescribing an
Effective Intensity of Rehabilitation.
AB - BACKGROUND: The proportional recovery rule suggests that current rehabilitation
practices may have limited ability to influence stroke recovery. However, the
appropriate intensity of rehabilitation needed to achieve recovery remains
unknown. Similarities between rodent and human recovery biomarkers may allow
determination of rehabilitation thresholds necessary to activate endogenous
biological recovery processes. OBJECTIVE: We determined the relative influence
that clinically relevant biomarkers of stroke recovery exert on functional
outcome. These biomarkers were then used to generate an algorithm that prescribes
individualized intensities of rehabilitation necessary for recovery of function.
METHODS: A retrospective cohort of 593 male Sprague-Dawley rats was used to
identify biomarkers that best predicted poststroke change in pellet retrieval in
the Montoya staircase-reaching task using multiple linear regression. Prospective
manipulation of these factors using endothelin-1-induced stroke (n = 49) was used
to validate the model. RESULTS: Rehabilitation was necessary to reliably predict
recovery across the continuum of stroke severity. As infarct volume and initial
impairment increased, more intensive rehabilitation was required to engage
recovery. In this model, we prescribed the specific dose of daily rehabilitation
required for rats to achieve significant motor recovery using the biomarkers of
initial poststroke impairment and infarct volume. CONCLUSIONS: Our algorithm
demonstrates an individualized approach to stroke rehabilitation, wherein imaging
and functional performance measures can be used to develop an optimized
rehabilitation paradigm for rats, particularly those with severe impairments.
Exploring this approach in human patients could lead to an increase in the
proportion of individuals experiencing recovery of lost motor function
poststroke.
PMID- 29334832
TI - Novel Mortality Markers for Critically Ill Patients.
AB - AIM: Inflammatory markers, such as the neutrophil to lymphocyte ratio (NLR) and
platelet to lymphocyte ratio (PLR), derived from a complete blood count have
recently attracted attention as potential markers of morbidity and mortality in
various diseases. The aim of the present study was to assess the usefulness of
the NLR and PLR as markers of hospital stay and mortality of patients in
intensive care units (ICUs). METHODS: Patients treated in the ICU of our
institution between October 2016 and August 2017 were enrolled in the study.
After obtaining approval from the institutional committee, patient data were
sourced from the institution's computerized database and retrospectively
analyzed. The patients were assigned to 2 groups according to the outcomes:
survivors and deceased. RESULTS: The NLR of survivors and deceased patients was
2.06 (1.18-21.68) and 10.42 (2.85-48.2), respectively. The NLR was significantly
elevated in deceased patients as compared with that of survivors ( P < .001).
Similarly, the median PLR of patients in the deceased group (268.9 [150-3000])
was significantly higher than that of patients in the survivor group (55.7 [11.8
152.5]). The difference in the PLR between groups was significant ( P < .001).
CONCLUSION: Both the NLR and PLR, as well as C-reactive protein, predicted
mortality in this critically ill population. The PLR and NLR are easy-to-measure,
inexpensive markers. Physicians should be aware of elevations in PLR and NLR in
patient care in ICUs.
PMID- 29334833
TI - Silver nanoparticles induce neurotoxicity in a human embryonic stem cell-derived
neuron and astrocyte network.
AB - Silver nanoparticles (AgNPs) are among the most extensively used nanoparticles
and are found in a variety of products. This ubiquity leads to inevitable
exposure to these particles in everyday life. However, the effects of AgNPs on
neuron and astrocyte networks are still largely unknown. In this study, we used
neurons and astrocytes derived from human embryonic stem cells as a cellular
model to study the neurotoxicity that is induced by citrate-coated AgNPs (AgSCs).
Immunostaining with the astrocyte and neuron markers, glial fibrillary acidic
protein and microtubule-associated protein-2 (MAP2), respectively, showed that
exposure to AgSCs at the concentration of 0.1 ug/mL increased the
astrocyte/neuron ratio. In contrast, a higher concentration of AgSCs (5.0 ug/ml)
significantly changed the morphology of astrocytes. These results suggest that
astrocytes are sensitive to AgSC exposure and that low concentrations of AgSCs
promote astrogenesis. Furthermore, our results showed that AgSCs reduced neurite
outgrowth, decreased the expression of postsynaptic density protein 95 and
synaptophysin, and induced neurodegeneration in a concentration-dependent manner.
Our findings additionally suggest that the expression and phosphorylation status
of MAP2 isoforms, as modulated by the activation of the Akt/glycogen synthase
kinase-3/caspase-3 signaling pathway, may play an important role in AgSC-mediated
neurotoxicity. We also found that AgNO3 exposure only slightly reduced neurite
outgrowth and had little effect on MAP2 expression, suggesting that AgSCs and
AgNO3 have different neuronal toxicity mechanisms. In addition, most of these
effects were reduced when the cell culture was co-treated with AgSCs and the
antioxidant ascorbic acid, which implies that oxidative stress is the major cause
of AgSC-mediated astrocytic/neuronal toxicity and that antioxidants may have a
neuroprotective effect.
PMID- 29334835
TI - National approaches to promote sports and physical activity in adults with
disabilities: examples from the Netherlands and Canada.
AB - PURPOSE: This study described how the Dutch and Canadian governments promote high
performance sports, recreational sports, and physical activity (PA) among adults
with disabilities on a national level. METHODS: An internet-based study was
conducted to identify and select relevant documents and websites containing
information about the national approach to promote disability sports and physical
activities in the Netherlands and Canada. RESULTS: Both governments promote high
performance sports in similar ways, but use different strategies to promote
recreational sports and physical activities. The Dutch approach is characterized
by using time-limited programs focusing on enhancement of sports infrastructure
and inter-sector collaboration in which municipalities have key roles. The
Canadian government promotes recreational sports in disabled populations by
supporting programs via bilateral agreements with provinces and territories.
Furthermore, the level of integration of disability sports into mainstream sports
differs between countries. CONCLUSIONS: The findings of this study may inspire
policy makers from different countries to learn from one another's policies in
order to optimize national approaches to promote disability sports and PA on all
levels. Implications for rehabilitation It is recommended for policy makers of
national governments to develop and implement policy programs that promote sports
and physical activities among people with disabilities because of its potential
impact on functioning, participation, quality of life, and health. Insight into
national approaches to promote sport and physical activities is relevant for
rehabilitation practice to understand ongoing opportunities for people with
disabilities to stay physically active after rehabilitation through participation
in home and/or community-based sport and physical activities. It seems worthwhile
to integrate activities to promote sport and physical activities in
rehabilitation in such a way that it fits with the current governmental approach.
It is recommended to set up international collaborations to develop and share
knowledge about effective and sustainable national approaches to promote sports
and physical activities among people with disabilities.
PMID- 29334834
TI - Mild Jugular Compression Collar Ameliorated Changes in Brain Activation of
Working Memory after One Soccer Season in Female High School Athletes.
AB - Recent neuroimaging studies have suggested that repetitive subconcussive head
impacts, even after only one sport season, may lead to pre- to post-season
structural and functional alterations in male high school football athletes.
However, data on female athletes are limited. In the current investigation, we
aimed to (1) assess the longitudinal pre- to post-season changes in functional
MRI (fMRI) of working memory and working memory performance, (2) quantify the
association between the pre- to post-season change in fMRI of working memory and
the exposure to head impact and working memory performance, and (3) assess
whether wearing a neck collar designed to reduce intracranial slosh via mild
compression of the jugular veins can ameliorate the changes in fMRI brain
activation observed in the female high school athletes who did not wear collars
after a full soccer season. A total of 48 female high school soccer athletes (age
range: 14.00-17.97 years) were included in the study. These athletes were
assigned to the non-collar group (n = 21) or to the collar group (n = 27). All
athletes undewent MRI at both pre-season and post-season. In each session, a fMRI
verbal N-Back task was used to engage working memory. A significant pre- to post
season increase in fMRI blood oxygen level dependent (BOLD) signal was
demonstrated when performing the N-back working memory task in the non-collar
group but not in the collar group, despite the comparable exposure to head
impacts during the season between the two groups. The collar group demonstrated
significantly smaller pre- to post-season change in fMRI BOLD signal than the non
collar group, suggesting a potential protective effect from the collar device.
Significant correlations were also found between the pre- to post-season increase
in fMRI brain activation and the decrease in task accuracy in the non-collar
group, indicating an association between the compensatory mechanism in underlying
neurophysiology and the alteration in the behavioral outcomes.
PMID- 29334836
TI - SNF5 deficiency induces apoptosis resistance by repressing SATB1 expression in
Sezary syndrome.
AB - SNF5, is a core member of the SWI/SNF chromatin remodeling complex. It's
deficiency leads to multiple types of aggressive cancer. Sezary syndrome, a
leukemic variant of cutaneous T-cell lymphoma, is characterized by its resistance
to apoptosis. Although the cause of apoptosis resistance is still poorly
understood, recent evidence has revealed the importance of SATB1 in the apoptosis
resistance of Sezary syndrome. In this study, we show that SNF5 is an upstream
regulator of SATB1 in several conditions and that both are deficient in Sezary
cells. Additionally, SNF5 not only controls the expression of SATB1, but also
utilizes SATB1 to recruit itself to specific sites. Overexpression of SNF5
induces SATB1 expression and partially reverse apoptosis resistance phenotype in
Sezary cells. These results suggest that both SNF5 and SATB1 may regulate
apoptosis-related genes in Sezary syndrome. Thus, targeting SWI/SNF complex may
represent a promising approach for Sezary syndrome therapy.
PMID- 29334837
TI - More expertise for a better perspective: Task and strategy-driven adaptive
neurofunctional reorganization for word production in high-performing older
adults.
AB - The suggestion that neurofunctional reorganization may contribute to preserved
language abilities is still emerging in aging studies. Some of these abilities,
such as verbal fluency (VF), are not unitary but instead rely on different
strategic processes that are differentially changed with age. Younger (n = 13)
and older adults (n = 13) carried out an overt self-paced semantic and
orthographic VF tasks within mixed fMRI design. Our results suggest that patterns
of brain activation sustaining equivalent performances could be underpinned by
different strategies facing brain changes during healthy aging. These main
findings suggest that temporally mediated semantic clustering and frontally
mediated orthographic switching were driven by evolutive neurofunctional
resources in high-performing older adults. These age-related activation changes
can appear to be compatible with the idea that unique neural patterns expressing
distinctive cognitive strategies are necessary to support older adults'
performance on VF tasks.
PMID- 29334838
TI - Monitoring of leukemia stem cells in chronic myeloid leukemia patients.
PMID- 29334839
TI - Bax inhibitor-1 is required for resisting the Early Brain Injury induced by
subarachnoid hemorrhage through regulating IRE1-JNK pathway.
AB - Background and Purpose Bax inhibitor-1 (BI-1) has been identified as a suppressor
of Bax-mediated cell apoptosis by regulation of endoplasmic reticulum stress
induced cell death. However, the role of BI-1 in Early Brain Injury (EBI) after
subarachnoid hemorrhage (SAH) remains unclear. In the present study, we aim to
explore the neuroprotective functions of BI-1 in EBI after SAH by using models of
SAH that induced endovascular perforation in rats. Method The neurological score,
brain water content and blood-brain barrier (BBB) permeability were evaluated
simultaneously as prognostic indicators. Western blot, RT-PCR and TUNEL staining
were performed to study the role and mechanisms of BI-1 in EBI after SAH. Results
We found that BI-1 knockdown increased histological injury and the percentages of
TUNEL-positive neuron in hippocampal, promoted the expressions of endoplasmic
reticulum (ER) stress proteins inositol-requiring enzyme 1alpha (IRE1alpha) and
TNF receptor-associated factor 2 (TRAF2), and increased the activation levels of
apoptosis signal-regulating kinase 1 (ASK1) and c-Jun N-terminal kinase (JNK) in
the hippocampus of SAH rats compared with rats in SAH + vehicle group. Conclusion
Our results indicate that BI-1 may participate in the regulation of EBI after SAH
by regulating IRE1-JNK pathway. Thus, the results suggest that BI-1 may be a
potential therapeutic target for SAH treatment.
PMID- 29334840
TI - Transcallosal conduction in paroxysmal kinesigenic dyskinesia.
AB - OBJECTIVES: Detecting whether a possible disequilibrium between the excitatory
and inhibitory interhemispheric interactions in paroxysmal kinesigenic dyskinesia
(PKD) exists. METHODS: This study assessed measures of motor threshold, motor
evoked potential latency, the cortical silent period, the ipsilateral silent
period and the transcallosal conduction time (TCT) in PKD patients. Data were
compared between the clinically affected hemisphere (aH) and the fellow
hemisphere (fH). RESULTS: The transcallosal conduction time from the aH to the fH
was 11.8 ms (range = 2.3-20.7) and 13.6 ms (range = 2.8-67.7) from the fH to the
aH. The difference in TCT in the affected side was significant (p = .019).
CONCLUSION: The findings demonstrated that, although inhibitory interneurons act
normally and symmetrically between the motor cortices and transcallosal
inhibition was normal and symmetrical between both sides, the onset of
transcallosal inhibition was asymmetrical. The affected hemisphere's inhibition
toward the unaffected hemisphere is faster compared to the inhibition provided by
the fellow hemisphere. These results are consistent with an inhibitory deficit in
the level of interhemispheric interactions. SIGNIFICANCE: This study revealed a
defect in inhibition of the motor axis could be responsible in the pathological
mechanisms of kinesigenic dyskinesia.
PMID- 29334841
TI - Tocilizumab in the treatment of myocardial infarction.
AB - Tocilizumab (TCZ) is an important biologic response modifier that rheumatologists
routinely employ in the treatment of several systemic autoimmune diseases. TCZ
binds to interleukin (IL)-6 receptors, inhibits cellular activation, and
mitigates inflammation by IL-6. In mid-2017, TCZ was approved by the US Food and
Drug Administration for its first nonrheumatologic condition, the treatment of
chimeric antigen receptor (CAR) T cell-induced severe or life-threatening
cytokine release syndrome in patients 2 years of age or older. With this approval
and with the increasing use of TCZ off-label for other non-rheumatologic
conditions such as Castleman's Disease and its variant TAFRO syndrome, where else
might TCZ be successfully utilized as treatment? Recently interesting data has
been published regarding possible use of TCZ in the treatment of myocardial
infarction. This review focuses on the role of IL-6 and its receptor in
myocardial inflammation and association with adverse clinical outcomes. Discussed
are one animal study and two human trials that have been published studying the
effect of TCZ in patients with acute myocardial infarction. Finally, this review
summarizes the current data and makes recommendations for future clinical trial
development in what hopefully will be a promising application of TCZ for a
serious nonrheumatologic condition.
PMID- 29334843
TI - High genetic diversity and low-population differentiation in the Patagonian sprat
(Sprattus fuegensis) based on mitochondrial DNA.
AB - The Patagonian sprat, Sprattus fuegensis, is a small pelagic marine fish that
inhabits the continental shelf along the coasts of Chilean Patagonian and
Argentina, a distribution that was highly impacted during the Last Glacial
Maximum (LGM). In order to identify how the LGM played a role on the current
observed genetic diversity and population structure of S. fuegensis, we analyzed
1438 nucleotide positions from the control region of 335 individuals collected at
12 sites across its distribution. Genetic diversity and differentiation indices
were calculated to identify population structure, and a Bayesian skyride plot
(BSRP) reconstruction was carried out to infer the historic population dynamics.
Extremely high genetic diversity was found at all locations analyzed, non
population structure was found across its distribution, and the BSRP showed two
increases in effective population size over time. Our outcomes suggest that the
current genetic diversity, population structure and population expansion may have
occurred during the medium and late Pleistocene.
PMID- 29334842
TI - A comprehensive review of endoscopic ultrasound core biopsy needles.
AB - INTRODUCTION: Endoscopic ultrasound (EUS)-guided tissue acquisition by-fine
needle biopsy (EUS-FNB) developed over the last two decades as an attempt to
overcome the limitations of fine needle aspiration (FNA). There are now three
commercially available second-generation FNB needles with different tip designs.
Areas covered: In this review the roles of EUS-FNA and FNB, the history and
evolution of the EUS core biopsy needle are addressed followed by a presentation
of currently available needles. Literature search was conducted using MEDLINE,
Controlled Trials Register, US Patent Registry, Google Scholar, and Conference
Abstracts. Expert commentary: While FNA remains the reference standard, it is
limited by the inability to retain stroma and associated cellular architecture in
biopsy samples. Histologic architecture is of paramount importance in providing a
molecular diagnosis and for accurate tumor staging. FNB offers a superior
diagnostic yield to FNA and initial experiences with the three commercially
available second-generation FNB needles show highly promising results.
PMID- 29334844
TI - The molecular signature of AML with increased ALDH activity suggests a stem cell
origin.
AB - Enrichment of leukemic blasts with a stem cell phenotype correlates with poor
survival in acute myeloid leukemia (AML). In this context, measurement of the
stem cell marker aldehyde-dehydrogenase (ALDH) activity can distinguish poor
prognosis cases with increased fractions of ALDH-positive cells (ALDH-numerous
AML) and favorable outcome cases with low percentages (ALDH-rare AML). It has
been shown that ALDH-numerous AML favor leukemic engraftment in
xenotransplantation assays which suggests increased leukemic stem cell (LSC)
potential. To test if this reflects an immature cell of origin, comparative gene
expression studies of CD34+ leukemic blasts were performed. This analysis
revealed increased expression of LSC and HSC signatures in ALDH-numerous AML,
whereas ALDH-rare AML were enriched for a progenitor signature. The enrichment of
stemness-associated transcriptional programs suggests that ALDH-numerous AML
derive from immature hematopoietic progenitors and offers an explanation for the
poor prognosis and therapy resistance of this subgroup which is likely caused by
inherited stem cell properties.
PMID- 29334845
TI - Neutrophil-to-lymphocyte ratio and mural nodule height as predictive factors for
malignant intraductal papillary mucinous neoplasms.
AB - BACKGROUND: Accurate preoperative prediction for malignant IPMN is still
challenging. The aim of this study was to investigate the validity of neutrophil
to-lymphocyte ratio (NLR) and mural nodule height (MNH) for predicting malignant
intraductal papillary mucinous neoplasm (IPMN). METHODS: The medical records of
60 patients who underwent pancreatectomy for IPMN were retrospectively reviewed.
RESULTS: NLR tended to be higher in malignant IPMN (median: 2.23) than in benign
IPMN (median: 2.04; p = .14). MNH was significantly greater in malignant IPMN
(median: 16 mm) than in benign IPMN (median: 8 mm; p < .01). The optimal cutoff
values for the NLR and MNH were 3.60 and 11 mm, respectively. The sensitivity and
specificity of NLR >=3.60 for predicting malignant IPMN were 40% and 93%, and
those of MNH >=11 mm were 73% and 77%, respectively. Univariate analysis revealed
that NLR >=3.60 (p < .01) and MNH >=11 mm (p < .01) were significant predictive
factors. On multivariate analysis, enhanced solid component was identified as an
independent factor, but NLR >=3.60 and MNH >=11 mm were not. CONCLUSIONS: NLR and
MNH are suboptimal tests in predicting malignant IPMN; however, they can be
useful to assist in clinical decision-making.
PMID- 29334846
TI - Scapular motion adaptations in junior overhead athletes: a three-dimensional
kinematic analysis in tennis players and non-overhead athletes.
AB - Adult overhead athletes without a history of shoulder injury show scapular
adaptations. There is a lack of detailed assessment of scapular kinematics in
junior overhead athletes. This study aims to investigate three-dimensional
scapular kinematics in junior overhead athletes. We recruited a total of 20
junior tennis players and 20 healthy children without participation in any
overhead sports in this study. Bilateral scapular kinematic data were recorded
using an electromagnetic tracking device for scapular plane glenohumeral
elevation. The data were further analysed at 30 degrees , 45 degrees , 60 degrees
, 90 degrees and 120 degrees during glenohumeral elevation and lowering.
Statistical comparisons of the data between groups (junior overhead athletes and
non-overhead athletes) and sides (serve dominant and non-dominant shoulders of
the overhead athletes) were analysed with the ANOVA. Comparisons showed that, in
general, the scapula was more upwardly rotated and anteriorly tilted in overhead
athletes when compared to non-overhead athletes, however there was no side-to
side differences when serve dominant and non-dominant shoulders compared in
junior overhead athletes. The serve dominant arm of junior overhead athletes had
alternations in scapular kinematics when compared with the non-overhead athletes.
These findings provide clinical evaluation implications and the need for
clinicians to assess for potential adaptations in junior overhead athletes.
PMID- 29334847
TI - Patient and family psychoeducation: Service development and implementation in a
center in Iran.
AB - BACKGROUND: Family and patient psychoeducation have demonstrated significant
improvement in clinical and social outcomes for patients suffering from severe
mental disorders and their families. However, these evidence-based practices are
not widely implemented at service delivery level and into routine clinical
practice, especially in less developed countries. AIM: The aim of this article is
to report the processes of development and implementation of a psychoeducational
service for patients with severe mental illnesses and their families in Iran.
METHOD: The program was developed at Roozbeh Hospital in Tehran, Iran. A group of
clinicians worked on the development phase of the program and drafting the
manuals. Then, a series of workshops and supervision sessions were held to train
group leaders for implementation of the group psychoeducation for patients and
families. In the pilot phase, the services were delivered to two groups of
patients and families, and then the manual was revised based on the feedback from
group leaders and participants. RESULTS: The program consisted of eight 90-minute
weekly patient group sessions and 6 weekly multiple family group sessions. Two
manuals for patient education (schizophrenia and bipolar disorder) were
developed. Several information sheets were developed and distributed during
different sessions of family and patient psychoeducation related to the content
of each session. Despite providing the hospital clinicians with the information
regarding these new services, less than 10% of the admitted patients were
referred by their clinicians. CONCLUSION: Feasibility and sustainability of the
program are affected by a number of factors. Low referral rate of clinicians,
limited resources of the hospital, issues related to stigma and logistic issues
are barriers in implementation of these services. Administrators' and clinicians'
understanding of the importance of patient and family psychoeducation seems to be
crucial in sustainability of such programs in routine service delivery.
PMID- 29334848
TI - The effect of social support, gratitude, resilience and satisfaction with life on
depressive symptoms among police officers following Hurricane Katrina.
AB - BACKGROUND: Police officers in the New Orleans geographic area faced a number of
challenges following Hurricane Katrina. AIM: This cross-sectional study examined
the effect of social support, gratitude, resilience and satisfaction with life on
symptoms of depression. METHOD: A total of 86 male and 30 female police officers
from Louisiana participated in this study. Ordinary least-square (OLS) regression
mediation analysis was used to estimate direct and indirect effects between
social support, gratitude, resilience, satisfaction with life and symptoms of
depression. All models were adjusted for age, alcohol intake, military experience
and an increase in the number of sick days since Hurricane Katrina. RESULTS: Mean
depressive symptom scores were 9.6 +/- 9.1 for females and 10.9 +/- 9.6 for
males. Mediation analyses indicates that social support and gratitude are
directly associated with fewer symptoms of depression. Social support also
mediated the relationships between gratitude and depression, gratitude and
satisfaction with life, and satisfaction with life and depression. Similarly,
resilience mediated the relationship between social support and fewer symptoms of
depression. CONCLUSION: Social support, gratitude and resilience are associated
with higher satisfaction with life and fewer symptoms of depression. Targeting
and building these factors may improve an officer's ability to address symptoms
of depression.
PMID- 29334849
TI - How to implement an enhanced recovery programme after colorectal surgery?
AB - INTRODUCTION: Although the concept of enhanced recovery after surgery was
introduced more than 20 years ago, its implementation in daily practice still
remains difficult. RESULTS: This article addresses bottlenecks and barriers to
the development of enhanced recovery programme (ERP). Barriers to the
implementation are multifactorial and are raised by the different actors of these
programmes: surgeons, anaesthetists, nurses, patients. Solutions and steps that
must be respected to succeed in introducing ERP in an hospital are proposed.
CONCLUSIONS: Large-scale implementation of ERP continues to face mainly lack of
trust and communication. Solutions exist and are based particularly on team work
and interdisciplinary collaboration.
PMID- 29334850
TI - An Immunopathological Evaluation of the Porcine Cholecyst Matrix as a Muscle
Repair Graft in a Male Rat Abdominal Wall Defect Model.
AB - With the increasing use of animal-based biomaterials for regenerative medical
applications, the need for their safety assessment is paramount. A porcine
cholecyst-derived scaffold (CDS), intended as a muscle repair graft, prepared by
a nondetergent/enzymatic method was engrafted in a rat abdominal wall defect
model. Host tissue-scaffold interface samples were collected 2, 8, and 16 weeks
postimplantation and evaluated by histopathology, immunohistochemistry, and
electron microscopy. The nature of the tissue reaction was compared with those
induced by a jejunum-derived scaffold (JDS) prepared by the same method and a
commercial-grade small intestinal submucosa (CSIS) scaffold. A study of the
immunopathological response in major lymphoid tissues and immunophenotyping for
M1 and M2 macrophages was performed at the host tissue-scaffold interface.
Further, "irritancy scores" for CDS and JDS were determined using CSIS as the
reference material. Both CDS and JDS appeared to be potential biomaterials for
muscle grafts, but the former stimulated a skeletal muscle tissue remodeling
response predominated by M2 macrophages. The data support the notion that
biomaterials with similar biocompatibility, based on local tissue response on
implantation, may cause differential immunogenicity. Additionally, CDS compared
to JDS and CSIS was found to be less immunotoxic.
PMID- 29334851
TI - What Are the Psychosocial Factors Associated With Migraine in the Child? Comorbid
Psychiatric Disorders, Family Functioning, Parenting Style, or Mom's Psychiatric
Symptoms?
AB - OBJECTIVE: Psychiatric diagnoses, parenting style, family functioning among
children and adolescents with migraine, and psychiatric symptoms of their mothers
were examined. METHODS: The K-SADS and other measurements were used to assess
psychiatric disorders in 50 children with migraine (aged 8-18) and matched 50
controls. RESULTS: At least one psychiatric disorder was diagnosed in 56% of the
migraine group. The presence of any psychiatric disorder in children (odds ratio
[OR] = 2.765, P = .027) and somatization symptoms in their mothers (OR = 2.061, P
= .025) were increasing the risk of migraine diagnosis. The parenting style scale
assessments revealed that parents in the migraine group grant their children less
autonomy. CONCLUSION: Psychiatric comorbidity, especially depression and anxiety
disorders, is more common in children with migraine. The frequency of eating
disorder is also higher. Evaluating comorbidity, family functioning, and
particularly affective responsiveness in migraine families may guide the
clinician to a targeted treatment plan.
PMID- 29334852
TI - Child Neurology: A Fragile Future.
PMID- 29334853
TI - Therapeutic Plasma Exchange Use in Pediatric Neurologic Disorders at a Tertiary
Care Center: A 10-Year Review.
AB - Pediatric neurologic conditions requiring therapeutic plasma exchange are rare in
children and literature is sparse. The study aims to determine the outcomes,
safety, and feasibility of therapeutic plasma exchange treatment in pediatric
neurologic disorders. This retrospective analysis looked at the outcomes and
safety of therapeutic plasma exchange in children (n = 50) with neurologic
conditions. Patient age ranged <1 to 19 years old with a mean of 10.35 years. Of
the 50 children treated with plasmapheresis, 26 patients received inpatient
rehabilitation. At discharge, functional status can be summarized as follows: 24
(48%) with mental status impairment, 10 (20%) with vision impairment, 19 (38%)
with bladder incontinence, and 37 (74%) with motor impairment. Three-month follow
up: 30% with mental status impairment, 10% with vision impairment, 18% with
bladder incontinence, and 52% with motor impairment. Therapeutic plasma exchange
is an effective and safe therapy for neurological conditions in the pediatric
population.
PMID- 29334854
TI - The Association Between Premorbid Conditions in School-Aged Children With
Prolonged Concussion Recovery.
AB - The association between preexisting anxiety, depression, and/or
neurodevelopmental disorders and symptom duration among younger children who
sustain concussions is not well known. The authors conducted a prospective cohort
study of 569 patients presenting to a pediatric neurology clinic with the
diagnosis of concussion. The authors measured associations between symptom
duration and premorbid conditions, as well as gender, age, mechanism of injury,
and other factors. Premorbid conditions were common in both age groups. On
univariate modeling female gender, age >12 years, and premorbid conditions were
associated with longer symptom duration. On multivariable modeling, females and
patients <=12 years old with a history of headaches, migraines, or a history of
psychiatric conditions took significantly longer to recover than those without
such conditions. Premorbid conditions are associated with a prolonged recovery
from concussion among those patients <=12 years old.
PMID- 29334856
TI - Stroke After Minor Head Trauma in Infants and Young Children With Basal Ganglia
Calcification: A Lenticulostriate Vasculopathy?
AB - The authors retrospectively reviewed charts of the children with basal ganglia
stroke who either had preceding minor head injury or showed basal ganglia
calcification on computed tomography (CT) scan. Twenty children, 14 boys and 6
girls were identified. Eighteen were aged between 7 months to 17 months.
Presentation was with hemiparesis in 17 and seizures in 3. Preceding minor head
trauma was noted in 18. Family history was positive in 1 case. Bilateral basal
ganglia calcification on CT scan was noted in 18. Brain magnetic resonance
imaging done in 18 infants showed acute or chronic infarcts in basal ganglia.
Results of other laboratory and radiological investigations were normal. Four
infants were lost to follow-up, 9 achieved complete or nearly completely
recovery, and 7 had persistent neurological deficits. Basal ganglia calcification
likely represents mineralized lenticulostriate arteries, a marker of
lenticulostriate vasculopathy. Abnormal lenticulostriate vessels are vulnerable
to injury and thrombosis after minor head trauma resulting in stroke.
PMID- 29334857
TI - Association of Neutrophil/Lymphocyte Ratio With Intravenous Immunoglobulin
Treatment in Children With Guillain-Barre Syndrome.
AB - Guillain-Barre syndrome (GBS) is an acute immune-mediated inflammatory
polyneuropathy of the peripheral nervous system. The authors aimed to investigate
whether the neutrophil/lymphocyte (N/L) and platelet/lymphocyte (P/L) ratios are
the parameters that associated with the drug treatment or severity of GBS. Twenty
seven children with GBS were retrospectively analyzed from the medical records of
patients who attended to the Pediatric Neurology Department of the Gaziantep
University Hospital. Biochemical and hematologic parameters were measured.
Leukocytes, neutrophils counts and N/L ratio were significantly higher before the
intravenous immunoglobulin treatment ( P < .001). However, there were no marked
differences in platelet count and P/L ratio. In addition, marked correlation was
observed between the N/L ratio after treatment and duration of weakness. The
results of the study showed that N/L ratio is significantly higher in GBS
patients, and reduces following with intravenous immunoglobulin treatment.
PMID- 29334858
TI - Case study of occupational mercury exposure during decontamination of turnaround
in refinery plant.
AB - Decontamination during turnaround (TA) can lead to high exposure to toxic
chemicals among workers. The decontamination process in refinery plants usually
comprises two types, i.e. steam and chemical decontamination. No matter the
method used, concentrations of toxic chemicals must be measured using the direct
reading instrument at the end of each decontamination cycle, which maybe repeated
several times until the readings are in acceptable level. To evaluate mercury
exposure of decontamination workers during decontamination procedure in
comprehensive turnaround of a refinery plant. Thirty personal and 16 area air
samples were collected using passive dosimeters and absorbent tubes,
respectively, during 8 days of the decontamination in comprehensive turnaround.
All samples were analyzed using inductively coupled plasma mass spectrometry (ICP
MS). Good practices and standard procedures for air sampling and analysis were
performed. The TWA concentrations were calculated and compared between steam and
chemical decontamination workers. All area samples were well below TLV (ND -
0.0016 mg/m3) while 5 of 14 samples collected at the steam team and 1 of 16
samples taken from the chemical team exceeded the TLV. The geometric mean (GSD)
of TWA concentration of the steam team was 0.0057(10.4906) mg/m3, which is about
twice as high as that of the chemical team, 0.0031(6.9422) mg/m3. The highest
mercury concentration, 0.1037 mg/m3, was collected from a steam decontamination
worker. According to the activities and observation, the steam team may have high
exposure while reading the chemical concentrations at the end of the
decontamination cycle.
PMID- 29334859
TI - Bayesian analysis of semi-parametric Cox models with latent variables.
AB - Respiratory cancer is one of the most commonly diagnosed cancers as well as the
leading cause of cancer death. Numerous efforts have been devoted to reducing the
death rate of respiratory cancer. In this article, we propose a semi-parametric
Cox model with latent variables to assess the effects of observed and latent risk
factors on survival time of respiratory cancer. The characteristics of latent
risk factors are characterized via multiple observed indicators by a confirmatory
factor analysis model. We develop a Bayesian estimation procedure to obtain the
estimates of parameters. Simulation shows that the performance of the proposed
methodology is satisfactory. The proposed method is applied to analyze the
Surveillance, Epidemiology, and End Results Program data set.
PMID- 29334860
TI - A mixed-effects, spatially varying coefficients model with application to multi
resolution functional magnetic resonance imaging data.
AB - Spatial resolution plays an important role in functional magnetic resonance
imaging studies as the signal-to-noise ratio increases linearly with voxel
volume. In scientific studies, where functional magnetic resonance imaging is
widely used, the standard spatial resolution typically used is relatively low
which ensures a relatively high signal-to-noise ratio. However, for pre-surgical
functional magnetic resonance imaging analysis, where spatial accuracy is
paramount, high-resolution functional magnetic resonance imaging may play an
important role with its greater spatial resolution. High spatial resolution comes
at the cost of a smaller signal-to-noise ratio. This begs the question as to
whether we can leverage the higher signal-to-noise ratio of a standard functional
magnetic resonance imaging study with the greater spatial accuracy of a high
resolution functional magnetic resonance imaging study in a pre-operative
patient. To answer this question, we propose to regress the statistic image from
a high resolution scan onto the statistic image obtained from a standard
resolution scan using a mixed-effects model with spatially varying coefficients.
We evaluate our model via simulation studies and we compare its performance with
a recently proposed model that operates at a single spatial resolution. We apply
and compare the two models on data from a patient awaiting tumor resection. Both
simulation study results and the real data analysis demonstrate that our newly
proposed model indeed leverages the larger signal-to-noise ratio of the standard
spatial resolution scan while maintaining the advantages of the high spatial
resolution scan.
PMID- 29334862
TI - The effects of an unanticipated side-cut on lower extremity kinematics and ground
reaction forces during a drop landing.
AB - Unanticipated direction to cut after landing may alter the lower extremity
landing biomechanics when performing landing motions. These alterations may
potentially increase the risk of ACL injury. The purpose of this study was to
determine if an unanticipated side-cut affects lower extremity landing
biomechanics in females. Eighteen recreational female athletes participated in
two blocks of testing: the first block of testing consisted of three acceptable
trials of anticipated dominant limb and non-dominant limb 45-degree diagonal
cutting after landing, which were performed in a counterbalanced order. The
second block of testing consisted of three acceptable trials of unanticipated
dominant limb and non-dominant limb diagonal cutting after landing. Data analysis
mainly focused on the dominant limb landing biomechanics. Unanticipated side-cut
landing, compared (paired t-test, p < 0.05) to the anticipated landings, resulted
in less hip abduction and tibial internal rotation angle at initial contact (IC)
and a lower maximum ankle inversion angle and a greater maximum knee abduction
angle, and knee and hip displacement. Also, greater posterior GRF and a longer
time to peak medial GRF were exhibited. These outcomes indicate that athletes may
adapt their landing mechanics to land unsafely when encountering an unanticipated
event.
PMID- 29334861
TI - COPD management by Swedish general practitioners - baseline results of the
PRIMAIR study.
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common cause of
suffering and death. Evidence-based management of COPD by general practitioners
(GPs) is crucial for decreasing the impact of the disease. Efficient strategies
include early diagnosis, smoking cessation and multimodal treatment. AIM: To
describe knowledge about and skills for managing COPD in GPs in Sweden. METHODS:
Prior to COPD education (the PRIMAIR Study), GPs at primary health care centers
(PHCCs) in Stockholm replied to 13 written, patient-case based, multiple choice
and free-text questions about COPD. Their knowledge and practical management
skills were assessed by assigned points that were analyzed with non-parametric
tests. RESULTS: Overall, 250 GPs at 34 PHCCs replied (89% response rate). Total
mean score was 9.9 (maximum 26). Scores were highest on 'management of smoking
cessation', 'follow-up after exacerbation' and 'diagnostic procedures'.
Spirometry was used frequently, although interpretation skills were suboptimal.
'Management of maintenance therapy', 'management of multimorbidity' and
'interprofessional cooperation' had mediocre scores. Scores were unrelated to
whether there was a nurse-led asthma/COPD clinic at the PHCC. CONCLUSIONS:
Swedish GPs' knowledge of COPD and adherence to current guidelines seem
insufficient. A nurse-led asthma/COPD clinic at the PHCC does not correlate with
sufficient COPD skills in the GPs. The relevance of this study to participants'
actual clinical practice and usefulness of easy-to-access clinical guides are
interesting topics for future investigation. To identify problem areas, we
suggest using questionnaires prior to educational interventions. Key Points
General practitioners (GPs) play a crucial role in providing evidence-based care
for patients with chronic obstructive pulmonary disease (COPD) who are treated in
primary care. Swedish GPs' knowledge about COPD and adherence to current
guidelines seem insufficient. Areas in greatest need of improvement are
spirometry interpretation, management of maintenance therapy, management of
multimorbidity in patients with COPD and interprofessional cooperation.
PMID- 29334863
TI - Totally Percutaneous Fenestration via the "Cheese-Wire" Technique to Facilitate
Endovascular Aneurysm Repair in Chronic Aortic Dissection.
AB - Here, we describe a totally percutaneous technique for longitudinal fenestration
of a chronic dissection flap in the setting of endovascular aneurysm repair
(EVAR), where the septum would otherwise preclude proper endograft sealing. This
technique is demonstrated in a 65-year-old man with a history of open surgical
repair of a Stanford type A aortic dissection, with a type B component that was
managed nonoperatively. The patient developed aneurysmal degeneration of the
infrarenal aorta during follow-up, and his anatomy was well suited for EVAR with
the exception of a chronic dissection flap dividing the proximal seal zone. Using
bilateral percutaneous access, a wire was passed through an existing fenestration
in the septum from true to false lumen and snared from the contralateral side.
Downward traction on this through-wire was then used as a "cheese-wire" to divide
the septum longitudinally and clear it from the proximal fixation site. Removal
of the septum provided an adequate proximal seal zone for the endograft, and
standard infrarenal EVAR was then performed with a good technical result.
Longitudinal fenestration using this technique is a useful adjunctive maneuver to
facilitate EVAR in the setting of chronic aortic dissection and is safely
achievable via a totally percutaneous approach.
PMID- 29334864
TI - Pain Assessment Documentation After Opioid Administration at a Community Teaching
Hospital.
AB - PURPOSE: To compare pain assessment documentation postopioid administration in
hospitalized patients before and after implementing nurse education. METHODS:
Patients 18 years and older were randomly selected for inclusion if they received
1 opioid dose while admitted to the hospital. Through retrospective chart review,
opioid data, including date and time, were collected for each opioid
administered. Pain score data, including time and date of documentation, were
recorded for analysis. The primary objective of this study was to determine
whether a nursing education intervention would improve documentation of pain
scores within an appropriate time frame postadministration of an opioid
medication. The intervention was a training presentation uploaded to the
institution's intranet with an assessment. The primary outcome was measured by
comparing the frequency by which nurses documented pain scores following opioid
administration before and after education. RESULTS: Three hundred twenty patients
(160 patients per time period) were evaluated. The percentage of pain scores
recorded within the appropriate assessment time following opioid administration
increased from 32.9% to 37.8% ( P = .003). The proportion of appropriate pain
score documentation increased 4.9% (95% confidence interval [CI]: 1.6%-8.2%).
CONCLUSION: An increase in the documentation of efficacy assessments after opioid
administration was demonstrated after nursing education. Further studies should
be done to identify additional strategies to increase monitoring as well as to
identify a benchmark for institutions with regard to pain management monitoring.
PMID- 29334865
TI - "I Never Would Have Caught That Before": Pharmacist Perceptions of Using Clinical
Decision Support for Antimicrobial Stewardship in the United States.
AB - To systematically improve the appropriateness of antibiotic prescribing,
antimicrobial stewardship programs have been developed. There is a paucity of
literature examining how pharmacists perform antimicrobial stewardship using a
clinical decision support system in a hospital setting. The purpose of this
qualitative study was to develop a model exploring how pharmacists perform
antimicrobial stewardship to identify areas for programmatic improvement.
Semistructured interviews were conducted across a health care system until
saturation of themes was reached. Pharmacists identified that self-efficacy and
time were vital for antimicrobial stewardship to be performed, while culture of
the hospital and attitude facilitated the process of stewardship. Antimicrobial
stewardship programs using clinical decision support tools should ensure
pharmacists have adequate time to address rules, provide easy-to-use resources
and training to support self-efficacy, and engage influential physicians to
support a culture of collaboration.
PMID- 29334866
TI - Follow-up of an age-period-cohort analysis on alcohol-related mortality trends in
Sweden 1970-2015 with predictions to 2025.
AB - BACKGROUND AND AIMS: Several studies have indicated that birth cohorts are
important in explaining trends in alcohol-related mortality. An earlier study
from Sweden with data up to 2002 showed that birth cohorts that grew up under
periods of more liberal alcohol policies had higher alcohol-related mortality
than those cohorts growing up under more restrictive time periods. In spite of
increasing alcohol consumption, predictions in 2002 also indicated lower alcohol
related mortality in the future. The aim of this study is to follow-up whether
the effects of birth cohorts and the predictions made for Sweden still holds
using data up to 2015. METHOD: The study comprised an age-period-cohort analysis
and predictions based on population predictions from Statistics Sweden. The
analysis was based on all alcohol-related deaths in the Swedish population
between 1969 and 2015 for the cohorts born in the decades 1920 through 1990. Data
were restricted to people 15-84 years of age. In total, the analysis covered
68,341 deaths and more than 284 million person-years. RESULTS: Male and female
cohorts born in the 1940s to 1950s exhibited the highest alcohol-related
mortality, while those born in the 1970s continued to have the lowest alcohol
related mortality rates. The predicted mortality rates for males are still
anticipated to decrease somewhat through 2025. CONCLUSIONS: The updated age
period-cohort analysis further supports the importance of focusing on restrictive
alcohol policies targeting adolescents.
PMID- 29334867
TI - Increasing prevalence of emotional symptoms in higher socioeconomic strata: Trend
study among Danish schoolchildren 1991-2014.
AB - AIMS: The aims of this study were: (a) to examine trends in daily emotional
symptoms among 11- to 15-year-olds from 1991 to 2014 in Denmark, and (b) to
examine trends in social inequality in daily emotional symptoms, that is, whether
the differences in prevalence between adolescents with parents of varying
occupational social class changed over time. METHODS: We combined seven
comparable cross-sectional Health Behaviour in School-aged Children surveys (
N=31,169). Daily emotional symptoms were measured by the HBSC Symptom Check List
and occupational social class (OSC) by students' reports about parents'
occupation. We calculated absolute (per cent) differences in emotional symptoms
between high and low OSC and relative differences by odds ratio for emotional
symptoms by parents' OSC. RESULTS: Eight per cent reported at least one daily
emotional symptoms, with an increasing trend from 1991 to 2014 ( p<0.001). The
prevalence in high, middle and low OSC was 6.2%, 7.4% and 10.6% ( p<0.0001). From
1991 to 2014, there was an increase in the prevalence of daily emotional symptoms
in high ( p<0.0001) and middle ( p<0.0001) but not low OSC ( p=0.4404). This
resulted in a diminishing absolute social inequality in emotional symptoms. The
statistical interaction between OSC and survey year was significant ( p=0.0023)
and suggests a diminishing relative social inequality in emotional symptoms from
1991 to 2014. CONCLUSIONS: There was an increasing prevalence of daily emotional
symptoms from 1991 to 2014 and a diminishing social inequality in prevalence of
daily emotional symptoms in terms of both absolute and relative social
inequality.
PMID- 29334868
TI - Biomechanical analyses of synchronised swimming standard and contra-standard
sculling.
AB - Synchronised swimming involves a variety of sculling movements essential for body
support and propulsion but its study is scarce. We aimed to biomechanically
compare standard and contra-standard sculling techniques, and to observe the
relationship between measures. Six synchronised swimmers performed two, 30 s
maximal intensity, fully tethered standard and contra-standard sculling motions.
Kinetic and kinematic data were obtained using a load-cell and underwater
cameras, respectively. Force decreased along both techniques' bouts, but no
differences in-between techniques were noted for any kinetic variables. Standard
sculling presented a higher cycle rate and a lower elbow mean angle than the
contra-standard sculling (2.4 +/- 0.3 vs. 2.0 +/- 0.2 cycles/s and 134.1 +/- 5.8
and 141.5 +/- 4.7 degrees , p < 0.05). In the standard sculling, by removing and
maintaining the variation between participants (rw and r, respectively), the
absolute mean force was directly related with cycle rate (rw = 0.60) and wrist
angular velocity during flexion (r = 0.82), while in the contra-standard
condition the force was inversely associated with wrist mean angle (r = -0.95)
and directly with hand speed (rw = 0.76), and elbow angular velocity (rw ~ 0.60).
Therefore, technique learning and training require different attention by coaches
and swimmers.
PMID- 29334869
TI - The influence of water depth on kinematic and spatiotemporal gait parameters
during aquatic treadmill walking.
AB - The purpose of this study was to investigate kinematic and spatiotemporal
variables of aquatic treadmill walking at three different water depths. A total
of 15 healthy individuals completed three two-minute walking trials at three
different water depths. The aquatic treadmill walking was conducted at waist
depth, chest-depth and neck-depth, while a customised 3-D underwater motion
analysis system captured their walking. Each participant's self-selected walking
speed at the waist level was used as a reference speed, which was applied to the
remaining two test conditions. A repeated measures ANOVA showed statistically
significant differences among the three walking conditions in stride length,
cadence, peak hip extension, hip range of motion (ROM), peak ankle plantar
flexion and ankle ROM (All p values < 0.05). The participants walked with
increased stride length and decreased cadence during neck level as compared to
waist and chest level. They also showed increased ankle ROM and decreased hip ROM
as the water depth rose from waist and chest to the neck level. However, our
study found no significant difference between waist and chest level water in all
variables. Hydrodynamics, such as buoyancy and drag force, in response to changes
in water depths, can affect gait patterns during aquatic treadmill walking.
PMID- 29334870
TI - Images in Vascular Medicine. Linear morphea masquerading as superficial
thrombophlebitis.
PMID- 29334871
TI - Biomonitoring of arsenic in woodworkers exposed to CCA and evaluation of other
non-occupational sources in Uruguay.
AB - In Uruguay wood-impregnation plants use chromated copper arsenate (CCA) as
preservative applying good manufacture practices (GMP). This study aims a
retrospective evaluation of toxicologically relevant species levels in CCA
exposed woodworker's urine (As-U) and an assessment of the effects of work risk
factors and non-occupational sources in As-U of workers from a selected plant.
From 2014 to 2016, As-U in 212 urine samples (As-U) of 73 woodworkers from six
CCA impregnation plants were determined. In one of these plants, 35 workers were
interviewed to obtain individual data of work tasks, lifestyles, diet, habits,
etc. that may contribute to their overall exposure to Arsenic. Responses were
statistically evaluated. Out of the 212 urine samples from 73 woodworkers, 96%
showed lower levels of As-U than those established by health regulations (<35MUgL
1). According to their work tasks 34% of 35 surveyed workers showed high exposure
risk to As and 29% moderate exposure risk. Although they have lower levels of As
U owing to their personal protective equipment, As-U significantly correlate to
work risk factors. Consumption of bottled water could also contribute to As-U
levels as a non-occupational source. These results confirm that efforts of
Uruguayan authorities to promote GMP were successful and justify the importance
and frequency of As-U systematic biomonitoring for occupational risk assessment.
A significant accomplishment of this work is that non-occupational sources of As
like bottled water consumption should also be considered in future studies.
PMID- 29334872
TI - Labelling as reference Centre of GRACE (Groupe francophone de Rehabilitation
Amelioree apres ChirurgiE) for colorectal surgery: its impact on the
implementation of enhanced recovery programme at the University Hospital of
Liege.
AB - BACKGROUND: Enhanced recovery programme (ERP) has been used in our hospital since
2005 for selected colorectal surgeries. Since October 2015, after labelling as
GRACE reference centre, we included all patients scheduled for elective
colorectal surgery in this programme. We assessed the impact of our labelling on
the implementation of ERP. METHODS: Results of our first 100 patients entered in
the GRACE database were analyzed: length of stay, complications, readmission,
adherence to the protocol. These results are compared to those of the last 100
patients undergoing colorectal surgery before our labelling. RESULTS: Patients'
characteristics in both groups were similar. The complications rate was similar
in both groups. The global length of hospital stay was 4 [5] days vs. 8.5 [8]
(median [IQR]), respectively after and before labelling; p < .001. The duration
of hospitalization for the different subgroups (age, surgical approach, types of
surgery) were significantly shorter after our labelling (respectively: p < .001,
p < .01, and p < .05). CONCLUSIONS: Our results demonstrate that labelling as
reference centre increases the efficiency of the implementation of ERP. The fact
that all subgroups of patients benefit from ERP must encourage inclusion of all
patients undergoing elective colorectal surgery in ERP.
PMID- 29334873
TI - Nobiletin prevents cadmium-induced neuronal apoptosis by inhibiting reactive
oxygen species and modulating JNK/ERK1/2 and Akt/mTOR networks in rats.
AB - Objectives Cadmium (Cd), an extremely noxious environmental pollutant is known to
induce oxidative stress leading to neurodegenerative diseases. Nobiletin, a
citrus flavonoid is reported to possess various pharmacological properties. This
study investigates the effects of nobiletin over Cd-induced neuronal apoptosis in
rodent experimental model. Methods To separate group of male Sprague Dawley rats,
Cd (2 mL/kg/day) was subcutaneously injected for one month which results in a
dose level of 1 mg/kg Cd. Couple of days prior to Cd injection, the treatment
group rats regularly received nobiletin (50, 100, or 200 mg/kg b.wt) orally
through the study period. Results Cd-induced ROS levels and malondialdehyde (MDA)
content were inhibited by nobiletin and improved glutathione levels. Nobiletin
reduced neuronal apoptosis induced by Cd and raised cleaved caspase-3 levels.
Intriguingly, nobiletin blocked JNK and Erk1/2 phosphorylation and down-regulated
the pathways. Raised expression of kinases - MKK and ASK1 were reduced by
nobiletin. Discussion The suppressed expression of phosphatases - PP2A and PP5
were up-regulated on nobiletin treatment. Nobiletin significantly blocked the
activation of Akt/mTOR signaling. Enhanced phosphorylation of S6K1, Akt, and 4E
BP1 induced by Cd was significantly inhibited by nobiletin. The raised levels of
raptor and rictor proteins were remarkably down-regulated on nobiletin treatment.
Collectively, the observations of this study indicate protective effects of
nobiletin against Cd-induced neurotoxicity.
PMID- 29334874
TI - A Comparison of Collaborative Care Outcomes in Two Health Care Systems: VA
Clinics and Federally Qualified Health Centers.
AB - OBJECTIVE: Collaborative care for depression results in symptom reduction when
compared with usual care. No studies have systematically compared collaborative
care outcomes between veterans treated at Veterans Affairs (VA) clinics and
civilians treated at publicly funded federally qualified health centers (FQHCs)
after controlling for demographic and clinical characteristics. METHODS: Data
from two randomized controlled trials that used a similar collaborative care
intervention for depression were combined to conduct post hoc analyses (N=759).
The Telemedicine-Enhanced Antidepressant Management intervention was delivered in
VA community-based outpatient clinics (CBOCs), and the Outreach Using
Telemedicine for Rural Enhanced Access in Community Health intervention was
delivered in FQHCs. Multivariate logistic regression was used to determine
whether veteran status moderated the effect of the intervention on treatment
response (>50% reduction in symptoms). RESULTS: There was a significant main
effect for intervention (odds ratio [OR]=5.23, p<.001) and a moderating effect
for veteran status, with lower response rates among veterans compared with
civilians (OR=.21, p=.01). The addition of variables representing medication
dosage and number of mental health and general health appointments did not
influence the moderating effect. A sensitivity analysis stratified by gender
found a significant moderating effect of veteran status for men but not women.
CONCLUSIONS: Veteran status was a significant moderator of collaborative care
effectiveness for depression, indicating that veterans receiving collaborative
care at a CBOC are at risk of nonresponse. Unmeasured patient- or system-level
characteristics may contribute to poorer response among veterans.
PMID- 29334875
TI - Summary of Key Issues Raised in the Technology for Early Awareness of Addiction
and Mental Illness (TEAAM-I) Meeting.
AB - Technology provides an unparalleled opportunity to remove barriers to earlier
identification and engagement in services for mental and addictive disorders by
reaching people earlier in the course of illness and providing links to just-in
time, cost-effective interventions. Achieving this opportunity, however, requires
stakeholders to challenge underlying assumptions about traditional pathways to
mental health care. In this Open Forum, the authors highlight key issues
discussed in the Technology for Early Awareness of Addiction and Mental Illness
(TEAAM-I) meeting-held October 13-14, 2016, in New York City-that are related to
three identified areas in which technology provides important and unique
opportunities to advance early identification, increase service engagement, and
decrease the duration of untreated mental and addictive disorders.
PMID- 29334877
TI - Utilization of Mental Health Services by Children Displaced by Hurricane Katrina.
AB - OBJECTIVE: This study examined changes in utilization of mental health services
after Hurricane Katrina among children with preexisting conditions who were
displaced from their homes in Louisiana disaster counties and resettled in Texas.
METHODS: A retrospective analysis was performed on Medicaid claims data for
101,950 children from 2004 to 2006. Pre-post changes in utilization of mental
health services by the displaced children and three control groups were compared.
The control groups were children from Louisiana disaster counties who were not
displaced, Louisiana children from nondisaster counties, and Texas children
enrolled in Medicaid. RESULTS: The proportion of children who had a prescription
fill for psychotropic medication and the average days' supply per child decreased
in each group, but the decreases were significantly larger for the displaced
group than for the control groups. The decreases in both measures were largest
for stimulants and antidepressants, the two most common medication classes. By
contrast, changes in the proportion of children with an encounter involving
psychiatric services and the average number of psychiatric services encounters
per child did not vary systematically across the displaced and control groups.
CONCLUSIONS: The contrast between the results for medication utilization and
encounters reveals a potential gap in post-Katrina provision of care. Although
the findings for encounters indicate that, on average, displaced children did not
experience a disruption in provider visits, the medication estimates suggest that
they often did not obtain pharmaceutical treatment. Future disaster responses may
be improved by addressing logistical impediments faced by disaster victims in
filling their prescriptions for psychiatric medications.
PMID- 29334876
TI - Three Nontraditional Approaches to Improving the Capacity, Accessibility, and
Quality of Mental Health Services: An Overview.
AB - To provide evidence for wider use of peer workers and other nonprofessionals, the
authors examined three approaches to mental health service provision-peer support
worker (PSW) programs, task shifting, and mental health first-aid and community
advocacy organizations-summarizing their effectiveness, identifying similarities
and differences, and highlighting opportunities for integration. Relevant
articles obtained from PubMed, MEDLINE, and Google Scholar searches are
discussed. Studies indicate that PSWs can achieve outcomes equal to or better
than those achieved by nonpeer mental health professionals. PSWs can be
particularly effective in reducing hospital admissions and inpatient days and
engaging severely ill patients. When certain care tasks are given to individuals
with less training than professionals (task shifting), these staff members can
provide psychoeducation, engage service users in treatment, and help them achieve
symptom reduction and manage risk of relapse. Mental health first-aid and
community organizations can reduce stigma, increase awareness of mental health
issues, and encourage help seeking. Most PSW programs have reported
implementation challenges, whereas such challenges are fewer in task-shifting
programs and minimal in mental health first-aid. Despite challenges in scaling
and integrating these approaches into larger systems, they hold promise for
improving access to and quality of care. Research is needed on how these
approaches can be combined to expand a community's capacity to provide care.
Because of the serious shortage of mental health providers globally and the
rising prevalence of mental illness, utilizing nontraditional providers may be
the only solution in both low- and high-resource settings, at least in the short
term.
PMID- 29334878
TI - The Use of Standardized Discharge in IPS Supported Employment Programs.
AB - OBJECTIVE: Some researchers have argued for using standardized discharge rules in
individual placement and support (IPS) based on time of unemployment. To evaluate
potential adverse outcomes of these rules, the authors examined time to first job
over 24 months in a large randomized controlled study. METHODS: This secondary
analysis of 2,055 participants in the Mental Health Treatment Study, using
bootstrapping and survival analysis, estimated and compared the likelihood of
finding a first job in the IPS and control groups during each quarter over 24
months. RESULTS: Although the likelihood of obtaining a first job declined over
time, IPS recipients were more likely than participants in a control group to
find first jobs for at least 18 months. CONCLUSIONS: Use of standardized
discharge rules in IPS, based on initial periods of unemployment, may be cost
effective but would penalize recipients who respond more slowly. Natural
attrition may be a more sensitive and ethical way to create capacity.
PMID- 29334879
TI - The Extent to Which Psychiatrists Diagnose and Treat Substance Use Disorders.
PMID- 29334880
TI - Variability in Clinical Outcomes for Youths Treated for Subthreshold Severe
Mental Disorders at an Early Intervention Service.
AB - OBJECTIVE: The study assessed the longitudinal clinical and functional outcomes
of young people receiving early intervention services for subthreshold
manifestations of severe mental disorders at a youth mental health service in
Sydney, Australia. METHODS: The six-month, prospective, longitudinal study
collected data on clinical outcomes of 243 young people treated for subsyndromal
presentations of putative major mental disorders. Reliable change index scores
and effect sizes were calculated to compare results at baseline, three months,
and six months for measures of symptoms (Brief Psychiatric Rating Scale [BPRS]),
psychological distress (Kessler 10 [K10]), and social functioning (Social and
Occupational Functioning Assessment Scale [SOFAS]). RESULTS: There was
variability in outcomes across each of the outcome measures, with 25%, 33%, and
23% of patients showing reliable improvement and 9%, 13%, and 5% showing reliable
deterioration for the SOFAS, K10, and BPRS, respectively. Many individuals did
not show linear improvement or deterioration, with reliable change within
individuals varying significantly between the zero- to three-month and three- to
six-month time points. After the analyses were controlled for covariates,
baseline severity or impairment and number of sessions with a psychiatrist or
psychologist contributed a small (4%-8%) but significant amount to the total
variance in outcomes at six months. CONCLUSIONS: Most individuals did not show
significant deterioration, and about one in four showed reliable improvement by
six months. However, individual patterns of change were diverse, highlighting the
importance of further research into factors that influence treatment outcomes
among youths with subthreshold presentations of severe mental disorders.
PMID- 29334881
TI - A Proactive Behavioral Health Service Model to Address Use of Constant
Observation in a General Hospital.
AB - In hospitals, use of constant observation (CO) causes significant economic burden
without demonstrated reduction in adverse events. A novel quality improvement
(QI) project was developed to reduce use of CO by integrating proactive
behavioral health management of all patients requiring CO in a general hospital.
Specific nonpharmacologic and pharmacologic interventions used in this project,
which included 491 patients, are discussed. Data collected were compared with
data from a baseline period before project implementation. The average monthly
cost of observers was reduced by 33%, and length of stay was reduced 15% without
increased complications. Using QI to develop proactive and consistent involvement
of a designated behavioral health team and potentially reproducible care
protocols for patients requiring CO resulted in improvement in quality, reduction
in cost, and enhanced behavioral health integration in the general hospital.
PMID- 29334882
TI - Federal Parity and Access to Behavioral Health Care in Private Health Plans.
AB - OBJECTIVE: The 2008 Mental Health Parity and Addiction Equity Act (MHPAEA) sought
to improve access to behavioral health care by regulating health plans' coverage
and management of services. Health plans have some discretion in how to achieve
compliance with MHPAEA, leaving questions about its likely effects on health plan
policies. In this study, the authors' objective was to determine how private
health plans' coverage and management of behavioral health treatment changed
after the federal parity law's full implementation. METHODS: A nationally
representative survey of commercial health plans was conducted in 60 market areas
across the continental United States, achieving response rates of 89% in 2010
(weighted N=8,431) and 80% in 2014 (weighted N=6,974). Senior executives at
responding plans were interviewed regarding behavioral health services in each
year and (in 2014) regarding changes. Student's t tests were used to examine
changes in services covered, cost-sharing, and prior authorization requirements
for both behavioral health and general medical care. RESULTS: In 2014, 68% of
insurance products reported having expanded behavioral health coverage since
2010. Exclusion of eating disorder coverage was eliminated between 2010 (23%) and
2014 (0%). However, more products reported excluding autism treatment in 2014
(24%) than 2010 (8%). Most plans reported no change to prior-authorization
requirements between 2010 and 2014. CONCLUSIONS: Implementation of federal parity
legislation appears to have been accompanied by continuing improvement in
behavioral health coverage. The authors did not find evidence of widespread
noncompliance or of unintended effects, such as dropping coverage of behavioral
health care altogether.
PMID- 29334883
TI - Renal outcomes in patients initiated on tenofovir disoproxil fumarate-based
antiretroviral therapy at a community health centre in Malawi.
AB - Tenofovir-based antiretroviral therapy (TDF ART) is the first-line regimen for
human immunodeficiency virus (HIV) in Africa. However, contemporary data on
nephrotoxicity are lacking. We determined the renal outcomes of patients
commenced on TDF ART in Malawi. ART-naive patients initiated on TDF ART at a
community health centre between 1 July 2013 and 31 December 2015 were included.
The estimated glomerular filtration rate (eGFR, Cockcroft-Gault) was recorded at
the initiation of therapy and over 18 months thereafter. The prevalence of renal
impairment at ART initiation (eGFR < 60 ml/min) and the incidence of
nephrotoxicity (eGFR < 50 ml/min) were determined. A total of 439 patients
(median age: 32 years; 317 [72.2%] female) were included. Twenty-one (4.8%)
patients had renal impairment at ART initiation; eGFR improved in all during
follow-up. Nephrotoxicity occurred in 17 (4.0%) patients with eGFR > 50 ml/min at
baseline, predominantly within the first six months of therapy. Increasing age
and diastolic hypertension (>100 mmHg) were independent risk factors for
nephrotoxicity development. The prevalence of kidney disease at ART initiation
was 4.8% and nephrotoxicity occurred in 4.0%. Some eGFR decline may have been due
to weight gain. Targeted monitoring of kidney function six months after TDF
initiation should be considered in Malawi.
PMID- 29334884
TI - Acroangiodermatitis mimicking Kaposi's sarcoma in an HIV-positive man.
AB - Kaposi's sarcoma (KS) is the commonest human immunodeficiency virus (HIV)-related
malignancy with its characteristic cutaneous morphological appearance and
histopathological features. However, it can be simulated by other co-morbid
opportunistic infections and unrelated dermatological conditions. We describe
such a case of acroangiodermatitis in an HIV co-infected man, based on exclusion
of KS histologically and the absence of human herpesvirus 8, the causative agent
of KS.
PMID- 29334885
TI - 2016 United Kingdom national guideline on the sexual health care of men who have
sex with men.
AB - This guideline is intended for use in UK Genitourinary medicine clinics and
sexual health services but is likely to be of relevance in all sexual health
settings, including general practice and Contraception and Sexual Health (CASH)
services, where men who have sex with men (MSM) seek sexual health care or where
addressing the sexual health needs of MSM may have public health benefits. For
the purposes of this document, MSM includes all gay, bisexual and all other males
who have sex with other males and both cis and trans men. This document does not
provide guidance on the treatment of particular conditions where this is covered
in other British Association for Sexual Health and HIV (BASHH) Guidelines but
outlines best practice in multiple aspects of the sexual health care of MSM.
Where prevention of sexually transmitted infections including HIV can be
addressed as an integral part of clinical care, this is consistent with the
concept of combination prevention and is included. The document is designed
primarily to provide guidance on the direct clinical care of MSM but also makes
reference to the design and delivery of services with the aim of supporting
clinicians and commissioners in providing effective services. Methodology This
document was produced in accordance with the guidance set out in the BASHH CEG's
document 'Framework for guideline development and assessment' published in 2010
at http://www.bashh.org/guidelines and with reference to the Agree II instrument.
Following the production of the updated framework in April 2015, the GRADE system
for assessing evidence was adopted and the draft recommendations were regraded.
Search strategy (see also Appendix 1) Ovid Medline 1946 to December 2014, Medline
daily update, Embase 1974 to December 2014, Pubmed NeLH Guidelines Database,
Cochrane library from 2000 to December 2014. Search language English only. The
search for Section 3 was conducted on PubMed to December 2014. Priority was given
to peer-reviewed papers published in scientific journals, although for many
issues evidence includes conference abstracts listed on the Embase database. In
addition, for 'Identification of problematic recreational drug and alcohol use'
section and 'Sexual problems and dysfunctions in MSM' section, searches included
PsycINFO. Methods Article titles and abstracts were reviewed and if relevant the
full text article was obtained. Priority was given to randomised controlled trial
and systematic review evidence, and recommendations made and graded on the basis
of best available evidence. Piloting and feedback The first draft of the
guideline was circulated to the writing group and to a small group of relevant
experts, third sector partners and patient representatives who were invited to
comment on the whole document and specifically on particular sections. The
revised draft was reviewed by the CEG and then reviewed by the BASHH
patient/public panel and posted on the BASHH website for public consultation. The
final draft was piloted before publication. Guideline update The guidelines will
be reviewed and revised in five years' time, 2022.
PMID- 29334886
TI - Factors associated with recent unsuppressed viral load in HIV-1-infected patients
in care on first-line antiretroviral therapy in South Africa.
AB - Unsuppressed viral load (VL) in patients on antiretroviral therapy (ART) occurs
when treatment fails to suppress a person's VL and is associated with decreased
survival and increased HIV transmission. The objective of this study was to
evaluate factors associated with unsuppressed VL (VL > 400 copies/ml) in patients
currently in care on first-line ART for >= 6 months attending South African
public healthcare facilities. We analysed electronic medical records of ART
patients with a VL result on record who started ART between January 2004 and
April 2016 from 271 public health facilities. We present descriptive and
multivariable logistic regression for unsuppressed VL at last visit using a
priori variables. We included 244,370 patients (69% female) on first-line ART in
April 2016 for >= 6 months. Median age at ART start was 33 years (7% were < 15
years old). Median duration on ART was 3.7 years. Adjusting for other variables,
factors associated with having an unsuppressed VL at the most recent visit among
patients in care included: (1) < 15 years old at ART start (adjusted odds ratio
[aOR]=2.58; 95% CI = 2.37, 2.81) versus 15-49 years at ART start, (2) male gender
(aOR = 1.29; 95% CI = 1.25, 1.35), (3) 6-12 months on ART versus longer (aOR =
1.34; 95% CI = 1.29, 1.40), (4) on tuberculosis (TB) treatment (aOR = 1.78; 95%
CI = 1.48, 2.13), and (5) prior ART exposure versus none (aOR = 1.20; 95% CI =
1.08, 1.32). Approximately 85% of the ART cohort who were in care had achieved
viral suppression, though men, youth/adolescents, patients with prior ART
exposure, those with short duration of ART, and patients on TB treatment had
increased odds of not achieving viral suppression. There is a need to develop and
evaluate targeted interventions for ART patients in care who are at high risk of
unsuppressed VL.
PMID- 29334887
TI - Bi-objective integer programming for RNA secondary structure prediction with
pseudoknots.
AB - BACKGROUND: RNA structure prediction is an important field in bioinformatics, and
numerous methods and tools have been proposed. Pseudoknots are specific motifs of
RNA secondary structures that are difficult to predict. Almost all existing
methods are based on a single model and return one solution, often missing the
real structure. An alternative approach would be to combine different models and
return a (small) set of solutions, maximizing its quality and diversity in order
to increase the probability that it contains the real structure. RESULTS: We
propose here an original method for predicting RNA secondary structures with
pseudoknots, based on integer programming. We developed a generic bi-objective
integer programming algorithm allowing to return optimal and sub-optimal
solutions optimizing simultaneously two models. This algorithm was then applied
to the combination of two known models of RNA secondary structure prediction,
namely MEA and MFE. The resulting tool, called BiokoP, is compared with the other
methods in the literature. The results show that the best solution (structure
with the highest F1-score) is, in most cases, given by BiokoP. Moreover, the
results of BiokoP are homogeneous, regardless of the pseudoknot type or the
presence or not of pseudoknots. Indeed, the F1-scores are always higher than 70%
for any number of solutions returned. CONCLUSION: The results obtained by BiokoP
show that combining the MEA and the MFE models, as well as returning several
optimal and several sub-optimal solutions, allow to improve the prediction of
secondary structures. One perspective of our work is to combine better mono
criterion models, in particular to combine a model based on the comparative
approach with the MEA and the MFE models. This leads to develop in the future a
new multi-objective algorithm to combine more than two models. BiokoP is
available on the EvryRNA platform: https://EvryRNA.ibisc.univ-evry.fr .
PMID- 29334888
TI - diceR: an R package for class discovery using an ensemble driven approach.
AB - BACKGROUND: Given a set of features, researchers are often interested in
partitioning objects into homogeneous clusters. In health research, cancer
research in particular, high-throughput data is collected with the aim of
segmenting patients into sub-populations to aid in disease diagnosis, prognosis
or response to therapy. Cluster analysis, a class of unsupervised learning
techniques, is often used for class discovery. Cluster analysis suffers from some
limitations, including the need to select up-front the algorithm to be used as
well as the number of clusters to generate, in addition, there may exist several
groupings consistent with the data, making it very difficult to validate a final
solution. Ensemble clustering is a technique used to mitigate these limitations
and facilitate the generalization and reproducibility of findings in new cohorts
of patients. RESULTS: We introduce diceR (diverse cluster ensemble in R), a
software package available on CRAN: https://CRAN.R-project.org/package=diceR
CONCLUSIONS: diceR is designed to provide a set of tools to guide researchers
through a general cluster analysis process that relies on minimizing subjective
decision-making. Although developed in a biological context, the tools in diceR
are data-agnostic and thus can be applied in different contexts.
PMID- 29334889
TI - Protein-protein interface hot spots prediction based on a hybrid feature
selection strategy.
AB - BACKGROUND: Hot spots are interface residues that contribute most binding
affinity to protein-protein interaction. A compact and relevant feature subset is
important for building machine learning methods to predict hot spots on protein
protein interfaces. Although different methods have been used to detect the
relevant feature subset from a variety of features related to interface residues,
it is still a challenge to detect the optimal feature subset for building the
final model. RESULTS: In this study, three different feature selection methods
were compared to propose a new hybrid feature selection strategy. This new
strategy was proved to effectively reduce the feature space when we were building
the prediction models for identifying hotspot residues. It was tested on eighty
two features, both conventional and newly proposed. According to the strategy,
combining the feature subsets selected by decision tree and mRMR (maximum
Relevance Minimum Redundancy) individually, we were able to build a model with 6
features by using a PSFS (Pseudo Sequential Forward Selection) process. Compared
with other state-of-art methods for the independent test set, our model had shown
better or comparable predictive performances (with F-measure 0.622 and recall
0.821). Analysis of the 6 features confirmed that our newly proposed feature
CNSV_REL1 was important for our model. The analysis also showed that the
complementarity between features should be considered as an important aspect when
conducting the feature selection. CONCLUSION: In this study, most important of
all, a new strategy for feature selection was proposed and proved to be effective
in selecting the optimal feature subset for building prediction models, which can
be used to predict hot spot residues on protein-protein interfaces. Moreover, two
aspects, the generalization of the single feature and the complementarity between
features, were proved to be of great importance and should be considered in
feature selection methods. Finally, our newly proposed feature CNSV_REL1 had been
proved an alternative and effective feature in predicting hot spots by our study.
Our model is available for users through a webserver:
http://zhulab.ahu.edu.cn/iPPHOT/ .
PMID- 29334891
TI - Tuning iteration space slicing based tiled multi-core code implementing
Nussinov's RNA folding.
AB - BACKGROUND: RNA folding is an ongoing compute-intensive task of bioinformatics.
Parallelization and improving code locality for this kind of algorithms is one of
the most relevant areas in computational biology. Fortunately, RNA secondary
structure approaches, such as Nussinov's recurrence, involve mathematical
operations over affine control loops whose iteration space can be represented by
the polyhedral model. This allows us to apply powerful polyhedral compilation
techniques based on the transitive closure of dependence graphs to generate
parallel tiled code implementing Nussinov's RNA folding. Such techniques are
within the iteration space slicing framework - the transitive dependences are
applied to the statement instances of interest to produce valid tiles. The main
problem at generating parallel tiled code is defining a proper tile size and tile
dimension which impact parallelism degree and code locality. RESULTS: To choose
the best tile size and tile dimension, we first construct parallel parametric
tiled code (parameters are variables defining tile size). With this purpose, we
first generate two nonparametric tiled codes with different fixed tile sizes but
with the same code structure and then derive a general affine model, which
describes all integer factors available in expressions of those codes. Using this
model and known integer factors present in the mentioned expressions (they define
the left-hand side of the model), we find unknown integers in this model for each
integer factor available in the same fixed tiled code position and replace in
this code expressions, including integer factors, with those including
parameters. Then we use this parallel parametric tiled code to implement the well
known tile size selection (TSS) technique, which allows us to discover in a given
search space the best tile size and tile dimension maximizing target code
performance. CONCLUSIONS: For a given search space, the presented approach allows
us to choose the best tile size and tile dimension in parallel tiled code
implementing Nussinov's RNA folding. Experimental results, received on modern
Intel multi-core processors, demonstrate that this code outperforms known closely
related implementations when the length of RNA strands is bigger than 2500.
PMID- 29334890
TI - Characterization of the late embryogenesis abundant (LEA) proteins family and
their role in drought stress tolerance in upland cotton.
AB - BACKGROUND: Late embryogenesis abundant (LEA) proteins are large groups of
hydrophilic proteins with major role in drought and other abiotic stresses
tolerance in plants. In-depth study and characterization of LEA protein families
have been carried out in other plants, but not in upland cotton. The main aim of
this research work was to characterize the late embryogenesis abundant (LEA)
protein families and to carry out gene expression analysis to determine their
potential role in drought stress tolerance in upland cotton. Increased cotton
production in the face of declining precipitation and availability of fresh water
for agriculture use is the focus for breeders, cotton being the backbone of
textile industries and a cash crop for many countries globally. RESULTS: In this
work, a total of 242, 136 and 142 LEA genes were identified in G. hirsutum, G.
arboreum and G. raimondii respectively. The identified genes were classified into
eight groups based on their conserved domain and phylogenetic tree analysis. LEA
2 were the most abundant, this could be attributed to their hydrophobic
character. Upland cotton LEA genes have fewer introns and are distributed in all
chromosomes. Majority of the duplicated LEA genes were segmental. Syntenic
analysis showed that greater percentages of LEA genes are conserved. Segmental
gene duplication played a key role in the expansion of LEA genes. Sixty three
miRNAs were found to target 89 genes, such as miR164, ghr-miR394 among others.
Gene ontology analysis revealed that LEA genes are involved in desiccation and
defense responses. Almost all the LEA genes in their promoters contained ABRE,
MBS, W-Box and TAC-elements, functionally known to be involved in drought stress
and other stress responses. Majority of the LEA genes were involved in secretory
pathways. Expression profile analysis indicated that most of the LEA genes were
highly expressed in drought tolerant cultivars Gossypium tomentosum as opposed to
drought susceptible, G. hirsutum. The tolerant genotypes have a greater ability
to modulate genes under drought stress than the more susceptible upland cotton
cultivars. CONCLUSION: The finding provides comprehensive information on LEA
genes in upland cotton, G. hirsutum and possible function in plants under drought
stress.
PMID- 29334892
TI - The genome of a prasinoviruses-related freshwater virus reveals unusual diversity
of phycodnaviruses.
AB - BACKGROUND: Phycodnaviruses are widespread algae-infecting large dsDNA viruses
and presently contain six genera: Chlorovirus, Prasinovirus, Prymnesiovirus,
Phaeovirus, Coccolithovirus and Raphidovirus. The members in Prasinovirus are
identified as marine viruses due to their marine algal hosts, while prasinovirus
freshwater relatives remain rarely reported. RESULTS: Here we present the
complete genomic sequence of a novel phycodnavirus, Dishui Lake Phycodnavirus 1
(DSLPV1), which was assembled from Dishui Lake metagenomic datasets. DSLPV1
harbors a linear genome of 181,035 bp in length (G + C content: 52.7%), with 227
predicted genes and 2 tRNA encoding regions. Both comparative genomic and
phylogenetic analyses indicate that the freshwater algal virus DSLPV1 is closely
related to the members in Prasinovirus, a group of marine algae infecting
viruses. In addition, a complete eukaryotic histone H3 variant was identified in
the genome of DSLPV1, which is firstly detected in phycodnaviruses and
contributes to understand the interaction between algal virus and its eukaryotic
hosts. CONCLUSION: It is in a freshwater ecosystem that a novel Prasinovirus
related viral complete genomic sequence is discovered, which sheds new light on
the evolution and diversity of the algae infecting Phycodnaviridae.
PMID- 29334893
TI - High-sensitivity HLA typing by Saturated Tiling Capture Sequencing (STC-Seq).
AB - BACKGROUND: Highly polymorphic human leukocyte antigen (HLA) genes are
responsible for fine-tuning the adaptive immune system. High-resolution HLA
typing is important for the treatment of autoimmune and infectious diseases.
Additionally, it is routinely performed for identifying matched donors in
transplantation medicine. Although many HLA typing approaches have been
developed, the complexity, low-efficiency and high-cost of current HLA-typing
assays limit their application in population-based high-throughput HLA typing for
donors, which is required for creating large-scale databases for transplantation
and precision medicine. RESULTS: Here, we present a cost-efficient Saturated
Tiling Capture Sequencing (STC-Seq) approach to capturing 14 HLA class I and II
genes. The highly efficient capture (an approximately 23,000-fold enrichment) of
these genes allows for simplified allele calling. Tests on five genes (HLA
A/B/C/DRB1/DQB1) from 31 human samples and 351 datasets using STC-Seq showed
results that were 98% consistent with the known two sets of digitals (field1 and
field2) genotypes. Additionally, STC can capture genomic DNA fragments longer
than 3 kb from HLA loci, making the library compatible with the third-generation
sequencing. CONCLUSIONS: STC-Seq is a highly accurate and cost-efficient method
for HLA typing which can be used to facilitate the establishment of population
based HLA databases for the precision and transplantation medicine.
PMID- 29334894
TI - Rare variant association analysis in case-parents studies by allowing for missing
parental genotypes.
AB - BACKGROUND: The development of next-generation sequencing technologies has
facilitated the identification of rare variants. Family-based design is commonly
used to effectively control for population admixture and substructure, which is
more prominent for rare variants. Case-parents studies, as typical strategies in
family-based design, are widely used in rare variant-disease association
analysis. Current methods in case-parents studies are based on complete case
parents data; however, parental genotypes may be missing in case-parents trios,
and removing these data may lead to a loss in statistical power. The present
study focuses on testing for rare variant-disease association in case-parents
study by allowing for missing parental genotypes. RESULTS: In this report, we
extended the collapsing method for rare variant association analysis in case
parents studies to allow for missing parental genotypes, and investigated the
performance of two methods by using the difference of genotypes between affected
offspring and their corresponding "complements" in case-parent trios and TDT
framework. Using simulations, we showed that, compared with the methods just only
using complete case-parents data, the proposed strategy allowing for missing
parental genotypes, or even adding unrelated affected individuals, can greatly
improve the statistical power and meanwhile is not affected by population
stratification. CONCLUSIONS: We conclude that adding case-parents data with
missing parental genotypes to complete case-parents data set can greatly improve
the power of our strategy for rare variant-disease association.
PMID- 29334895
TI - Challenges imposed by minor reference alleles on the identification and reporting
of clinical variants from exome data.
AB - BACKGROUND: The conventional variant calling of pathogenic alleles in exome and
genome sequencing requires the presence of the non-pathogenic alleles as genome
references. This hinders the correct identification of variants with minor and/or
pathogenic reference alleles warranting additional approaches for variant
calling. RESULTS: More than 26,000 Exome Aggregation Consortium (ExAC) variants
have a minor reference allele including variants with known ClinVar disease
alleles. For instance, in a number of variants related to clotting disorders, the
phenotype-associated allele is a human genome reference allele (rs6025, rs6003,
rs1799983, and rs2227564 using the assembly hg19). We highlighted how the current
variant calling standards miss homozygous reference disease variants in these
sites and provided a bioinformatic panel that can be used to screen these
variants using commonly available variant callers. We present exome sequencing
results from an individual with venous thrombosis to emphasize how pathogenic
alleles in clinically relevant variants escape variant calling while non
pathogenic alleles are detected. CONCLUSIONS: This article highlights the
importance of specialized variant calling strategies in clinical variants with
minor reference alleles especially in the context of personal genomes and exomes.
We provide here a simple strategy to screen potential disease-causing variants
when present in homozygous reference state.
PMID- 29334896
TI - Global analysis of prokaryotic tRNA-derived cyclodipeptide biosynthesis.
AB - BACKGROUND: Among naturally occurring small molecules, tRNA-derived
cyclodipeptides are a class that have attracted attention for their diverse and
desirable biological activities. However, no tools are available to link
cyclodipeptide synthases identified within prokaryotic genome sequences to their
chemical products. Consequently, it is unclear how many genetically encoded
cyclodipeptides represent novel products, and which producing organisms should be
targeted for discovery. RESULTS: We developed a pipeline for identification and
classification of cyclodipeptide biosynthetic gene clusters and prediction of
aminoacyl-tRNA substrates and complete chemical structures. We leveraged this
tool to conduct a global analysis of tRNA-derived cyclodipeptide biosynthesis in
93,107 prokaryotic genomes, and compared predicted cyclodipeptides to known
cyclodipeptide synthase products and all known chemically characterized
cyclodipeptides. By integrating predicted chemical structures and gene cluster
architectures, we created a unified map of known and unknown genetically encoded
cyclodipeptides. CONCLUSIONS: Our analysis suggests that sizeable regions of the
chemical space encoded within sequenced prokaryotic genomes remain unexplored.
Our map of the landscape of genetically encoded cyclodipeptides provides
candidates for targeted discovery of novel compounds. The integration of our
pipeline into a user-friendly web application provides a resource for further
discovery of cyclodipeptides in newly sequenced prokaryotic genomes.
PMID- 29334898
TI - seq-seq-pan: building a computational pan-genome data structure on whole genome
alignment.
AB - BACKGROUND: The increasing application of next generation sequencing technologies
has led to the availability of thousands of reference genomes, often providing
multiple genomes for the same or closely related species. The current approach to
represent a species or a population with a single reference sequence and a set of
variations cannot represent their full diversity and introduces bias towards the
chosen reference. There is a need for the representation of multiple sequences in
a composite way that is compatible with existing data sources for annotation and
suitable for established sequence analysis methods. At the same time, this
representation needs to be easily accessible and extendable to account for the
constant change of available genomes. RESULTS: We introduce seq-seq-pan, a
framework that provides methods for adding or removing new genomes from a set of
aligned genomes and uses these to construct a whole genome alignment. Throughout
the sequential workflow the alignment is optimized for generating a
representative linear presentation of the aligned set of genomes, that enables
its usage for annotation and in downstream analyses. CONCLUSIONS: By providing
dynamic updates and optimized processing, our approach enables the usage of whole
genome alignment in the field of pan-genomics. In addition, the sequential
workflow can be used as a fast alternative to existing whole genome aligners for
aligning closely related genomes. seq-seq-pan is freely available at
https://gitlab.com/rki_bioinformatics.
PMID- 29334897
TI - The genome sequence of the commercially cultivated mushroom Agrocybe aegerita
reveals a conserved repertoire of fruiting-related genes and a versatile suite of
biopolymer-degrading enzymes.
AB - BACKGROUND: Agrocybe aegerita is an agaricomycete fungus with typical mushroom
features, which is commercially cultivated for its culinary use. In nature, it is
a saprotrophic or facultative pathogenic fungus causing a white-rot of hardwood
in forests of warm and mild climate. The ease of cultivation and fructification
on solidified media as well as its archetypal mushroom fruit body morphology
render A. aegerita a well-suited model for investigating mushroom developmental
biology. RESULTS: Here, the genome of the species is reported and analysed with
respect to carbohydrate active genes and genes known to play a role during fruit
body formation. In terms of fruit body development, our analyses revealed a
conserved repertoire of fruiting-related genes, which corresponds well to the
archetypal fruit body morphology of this mushroom. For some genes involved in
fruit body formation, paralogisation was observed, but not all fruit body
maturation-associated genes known from other agaricomycetes seem to be conserved
in the genome sequence of A. aegerita. In terms of lytic enzymes, our analyses
suggest a versatile arsenal of biopolymer-degrading enzymes that likely account
for the flexible life style of this species. Regarding the amount of genes
encoding CAZymes relevant for lignin degradation, A. aegerita shows more
similarity to white-rot fungi than to litter decomposers, including 18 genes
coding for unspecific peroxygenases and three dye-decolourising peroxidase genes
expanding its lignocellulolytic machinery. CONCLUSIONS: The genome resource will
be useful for developing strategies towards genetic manipulation of A. aegerita,
which will subsequently allow functional genetics approaches to elucidate
fundamentals of fruiting and vegetative growth including lignocellulolysis.
PMID- 29334899
TI - Association between sequence variants in panicle development genes and the number
of spikelets per panicle in rice.
AB - BACKGROUND: Balancing panicle-related traits such as panicle length and the
numbers of primary and secondary branches per panicle, is key to improving the
number of spikelets per panicle in rice. Identifying genetic information
contributes to a broader understanding of the roles of gene and provides
candidate alleles for use as DNA markers. Discovering relations between panicle
related traits and sequence variants allows opportunity for molecular application
in rice breeding to improve the number of spikelets per panicle. RESULTS: In
total, 142 polymorphic sites, which constructed 58 haplotypes, were detected in
coding regions of ten panicle development gene and 35 sequence variants in six
genes were significantly associated with panicle-related traits. Rice cultivars
were clustered according to their sequence variant profiles. One of the four
resultant clusters, which contained only indica and tong-il varieties, exhibited
the largest average number of favorable alleles and highest average number of
spikelets per panicle, suggesting that the favorable allele combination found in
this cluster was beneficial in increasing the number of spikelets per panicle.
CONCLUSIONS: Favorable alleles identified in this study can be used to develop
functional markers for rice breeding programs. Furthermore, stacking several
favorable alleles has the potential to substantially improve the number of
spikelets per panicle in rice.
PMID- 29334900
TI - Process evaluation of the RaDIANT community study: a dialysis facility-level
intervention to increase referral for kidney transplantation.
AB - BACKGROUND: The Reducing Disparities in Access to kidNey Transplantation
Community Study (RaDIANT) was an End-Stage Renal Disease (ESRD) Network 6
developed, dialysis facility-level randomized trial testing the effectiveness of
a 1-year multicomponent education and quality improvement intervention in
increasing referral for kidney transplant evaluation among selected Georgia
dialysis facilities. METHODS: To assess implementation of the RaDIANT
intervention, we conducted a process evaluation at the conclusion of the
intervention period (January-December 2014). We administered a 20-item survey to
the staff involved with transplant education in 67 dialysis facilities randomized
to participate in intervention activities. Survey items assessed facility
participation in the intervention (fidelity and reach), helpfulness and
willingness to continue intervention activities (sustainability), suggestions for
improving intervention components (sustainability), and factors that may have
influenced participation and study outcomes (context). We defined high fidelity
to the intervention as completing 11 or more activities, and high participation
in an activity as having at least 75% participation across intervention
facilities. RESULTS: Staff from 65 of the 67 dialysis facilities completed the
questionnaire, and more than half (50.8%) reported high adherence (fidelity) to
RaDIANT intervention requirements. Nearly two-thirds (63.1%) of facilities
reported that RaDIANT intervention activities were helpful or very helpful, with
90.8% of facilities willing to continue at least one intervention component
beyond the study period. Intervention components with high participation
emphasized staff and patient-level education, including in-service staff
orientations, patient and family education programs, and patient educational
materials. Suggested improvements for intervention activities emphasized
addressing financial barriers to transplantation, with financial education
materials perceived as most helpful among RaDIANT educational materials.
Variation in facility-level fidelity of the RADIANT intervention did not
significantly influence the mean difference in proportion of patients referred
pre- (2013) and post-intervention (2014). CONCLUSIONS: We found high fidelity to
the RaDIANT multicomponent intervention at the majority of intervention
facilities, with sustainability of select intervention components at intervention
facilities and feasibility for dissemination across ESRD Networks. Future
modification of the intervention should emphasize financial education regarding
kidney transplantation and amend intervention components that facilities perceive
as time-intensive or non-sustainable. TRIAL REGISTRATION: Clinicaltrials.gov
number NCT02092727 . Registered 13 Mar 2014 (retrospectively registered).
PMID- 29334902
TI - Expression characterization of the herbicide tolerance gene Aryloxyalkanoate
Dioxygenase (aad-1) controlled by seven combinations of regulatory elements.
AB - BACKGROUND: Availability of well characterized maize regulatory elements for gene
expression in a variety of tissues and developmental stages provides effective
alternatives for single and multigene transgenic concepts. We studied the
expression of the herbicide tolerance gene aryloxyalkanoate dioxygenase (aad-1)
driven by seven different regulatory element construct designs including the
ubiquitin promoters of maize and rice, the actin promoters of melon and rice,
three different versions of the Sugarcane Bacilliform Badnavirus promoters in
association with other regulatory elements of gene expression. RESULTS: Gene
expression of aad-1 was characterized at the transcript and protein levels in a
collection of maize tissues and developmental stages. Protein activity against
its target herbicide was characterized by herbicide dosage response. Although
differences in transcript and protein accumulation were observed among the
different constructs tested, all events were tolerant to commercially relevant
rates of quizalafop-P-ethyl compared to non-traited maize under greenhouse
conditions. DISCUSSION: The data reported demonstrate how different regulatory
elements affect transcript and protein accumulation and how these molecular
characteristics translate into the level of herbicide tolerance. The level of
transcript detected did not reflect the amount of protein quantified in a
particular tissue since protein accumulation may be influenced not only by levels
of transcript produced but also by translation rate, post-translational
regulation mechanisms and protein stability. The amount of AAD-1 enzyme produced
with all constructs tested showed sufficient enzymatic activity to detoxify the
herbicide and prevent most herbicidal damage at field-relevant levels without
having a negative effect on plant health. CONCLUSIONS: Distinctive profiles of
aad-1 transcript and protein accumulation were observed when different regulatory
elements were utilized in the constructs under study. The ZmUbi and the SCBV
constructs showed the most consistent robust tolerance, while the melon actin
construct provided the lowest level of tolerance compared to the other regulatory
elements used in this study. These data provide insights into the effects of
differing levels of gene expression and how these molecular characteristics
translate into the level of herbicide tolerance. Furthermore, these data provide
valuable information to optimize future designs of single and multiple gene
constructs for maize research and crop improvement.
PMID- 29334901
TI - Monitoring vaccine and non-vaccine HPV type prevalence in the post-vaccination
era in women living in the Basilicata region, Italy.
AB - BACKGROUND: A large free-of-charge quadrivalent HPV (qHPV) vaccination program,
covering four cohorts annually (women 11, 14, 17 and 24 years), has been
implemented in Basilicata since 2007. This study evaluated vaccine and non
vaccine HPV prevalence 5-7 years post-vaccination program implementation in
vaccinated and unvaccinated women. METHODS: This population-based, cross
sectional study was conducted in the public screening centers of the Local Health
Unit in Matera between 2012 and 2014. Cervical samples were obtained for Pap and
HPV testing (HC2, LiPA Extra(r) assay) and participants completed a
sociodemographic and behavioral questionnaire. Detailed HPV vaccination status
was retrieved from the official HPV vaccine registry. HPV prevalence was
described overall, by type and vaccination status. The association between HPV
type-detection and risk/protective factors was studied. Direct vaccine protection
(qHPV vaccine effectiveness [VE]), cross-protection, and type-replacement were
evaluated in cohorts eligible for vaccination, by analyzing HPV prevalence of
vaccine and non-vaccine types according to vaccination status. RESULTS: Overall,
2793 women (18-50 years) were included, 1314 of them having been in birth cohorts
eligible for the HPV vaccination program (18- to 30-year-old women at enrolment).
Among the latter, qHPV vaccine uptake was 59% (at least one dose), with 94%
completing the schedule; standardized qHPV type prevalence was 0.6% in vaccinated
versus 5.5% in unvaccinated women (P <0.001); adjusted VE against vaccine type
infections was 90% (95% CI: 73%-96%) for all fully vaccinated women and 100% (95%
CI not calculable) in women vaccinated before sexual debut. No statistically
significant difference in overall high-risk HPV, high-risk non-vaccine HPV, or
any single non-vaccine type prevalence was observed between vaccinated and
unvaccinated women. CONCLUSIONS: These results, conducted in a post-vaccine era,
suggest a high qHPV VE and that a well-implemented catch-up vaccination program
may be efficient in reducing vaccine-type infections in a real-world setting. No
cross-protective effect or evidence of type-replacement was observed a few years
after HPV vaccine introduction.
PMID- 29334903
TI - A rare case of pericarditis and pleural empyema secondary to transdiaphragmatic
extension of pyogenic liver abscess.
AB - BACKGROUND: Transdiaphragmatic extension of pyogenic liver abscess is the rarest
cause of pericarditis and pleural empyema. It is a rapidly progressive and highly
lethal infection with mortality rates reaching 100% if left untreated. However,
the transmission route, treatment methods and prognosis have not been well
studied. CASE PRESENTATION: A 65-year-old male patient presented with a fever,
dyspnea, and right upper quadrant abdominal pain. Computed tomography of the
chest and abdomen showed huge liver abscess without full liquefaction in the left
lobe, large amount of left pleural effusion, and mild pericardial effusion, and
the patient was treated with parenteral antibiotics and pigtail insertion at the
left pleura. However, four days later, cardiac tamponade was developed and
surgical drainage of the abscess and pericardium was performed. Klebsiella
pneumonia was isolated from pleural empyema. Twenty-five days after surgery, the
patient was discharged without any complications. CONCLUSIONS: Herein, we report
a rare case of pleural empyema and pericarditis in that resulted from the
extension of huge pyogenic liver abscess. Early surgical treatment may have
prevented progression of the pericarditis to the more dismal purulent
pericarditis. We also review pertinent English literature on pericarditis as a
complication of PLA.
PMID- 29334904
TI - Association of Kidney Disease Quality of Life (KDQOL-36) with mortality and
hospitalization in older adults receiving hemodialysis.
AB - BACKGROUND: For older adults receiving dialysis, health-related quality of life
is not often considered in prognostication of death or future hospitalizations.
To determine if routine health-related quality of life measures may be useful for
prognostication, the objective of this study is to determine the extent of
association of Kidney Disease Quality of Life (KDQOL-36) subscales with adverse
outcomes in older adults receiving dialysis. METHODS: This is a longitudinal
study of 3500 adults aged >=75 years receiving dialysis in the United States in
2012 and 2013. We used Cox and Fine and Gray models to evaluate the association
of KDQOL-36 subscales with risk of death and hospitalization. We adjusted for
sociodemographic variables, hemodialysis access type, laboratory values, and
Charlson index. RESULTS: Three thousand one hundred thirty-two hemodialysis
patients completed the KDQOL-36. From KDQOL-36 completion date in 2012, 880
(28.1%) died and 2023 (64.6%) had at least one hospitalization over a median
follow-up of 512 and 203 days, respectively. Cohort members with a SF-12 physical
component summary (PCS) in the lowest quintile had an increased adjusted risk of
death [hazard ratio (HR), 1.55, 95% confidence interval (CI) 1.19-2.03] and
hospitalization (HR, 1.29, 95% CI 1.09-1.54) compared with those with scores in
the highest quintile. Cohort members with a SF-12 mental component summary in the
lowest quintile had an increased risk of hospitalization (HR, 1.39, 95% CI 1.17
1.65) compared with those in the highest quintile. In adjusted analyses, there
was no association between the symptoms of kidney disease, effects of kidney
disease, and burden of kidney disease subscales with time to death or first
hospitalization. Competing risk models showed similar HRs. CONCLUSIONS: Among the
KDQOL-36 subscales, the SF-12 PCS demonstrates the strongest association with
both death and future hospitalizations in older adults receiving hemodialysis
Further research is needed to assess the value this subscale may add to
prognostication.
PMID- 29334905
TI - Efficacy comparison of multi-phase CT and hepatotropic contrast-enhanced MRI in
the differential diagnosis of focal nodular hyperplasia: a prospective cohort
study.
AB - BACKGROUND: Different clinical behaviour influences the importance of
differentiating focal nodular hyperplasia (FNH) from other focal liver lesions
(FLLs). The aim of this study was to compare the efficacy of contrast-enhanced CT
and MRI in the diagnosis of FNH. METHODS: 157 patients with equivocal FLLs
detected in ultrasonography subsequently underwent multi-phase CT and MRI with
the use of hepatotropic contrast agent (Gd-BOPTA) in a 1.5 T scanner.
Examinations were evaluated by three independent readers. Diagnostic efficacy of
different radiological signs of FNH in both CT and MRI was compared and AFROC
analysis was performed. RESULTS: 4 hepatocellular adenomas, 95 hepatocellular
carcinomas, 98 hemangiomas, 138 metastases and 45 FNHs were diagnosed. In both CT
and MRI the radiological sign of the highest accuracy was the presence of the
central scar within FNH (0.93 and 0.96 relatively). The sum of two radiological
signs in MRI: homogeneous enhancement in hepatic arterial phase (HAP) and
enhancing lesion in hepatobiliary phase (HBP) was characterized with high values
of sensitivity (0.89), specificity (0.97), PPV (0.82), NPV (0.98) and accuracy
(0.96). After inclusion of clinical data into analysis the best discriminating
feature in MRI was the presence of enhancing lesion in HBP in patients without
cirrhosis. In this regard, efficacy parameters increased to 1.00, 0.99, 0.94,
1.00 and 0.99 accordingly. The area under the curve in AFROC analysis of MRI
performance was significantly larger than of CT (p = 0.0145). CONCLUSION: Gd
BOPTA-enhanced MRI is a more effective method in the differential diagnosis of
FNH than multi-phase CT.
PMID- 29334906
TI - Rationale and design of the CAROLINA(r) - cognition substudy: a randomised
controlled trial on cognitive outcomes of linagliptin versus glimepiride in
patients with type 2 diabetes mellitus.
AB - BACKGROUND: Type 2 diabetes mellitus is associated with cognitive dysfunction and
an increased risk of dementia. Linagliptin is a glucose-lowering agent of the
dipeptidyl peptidase-IV (DPP-IV) inhibitor class that is of particular interest
for the prevention of accelerated cognitive decline, because it may potentially
benefit the brain through pleiotropic effects, beyond glucose lowering. This
paper presents the design of a study that aims to establish if linagliptin is
superior to the sulfonylurea glimepiride in the prevention of accelerated
cognitive decline in patients with type 2 diabetes mellitus. METHODS: The
cognition substudy is an integral part of the ongoing event-driven, randomised,
double blind CARdiOvascular safety of LINAgliptin (CAROLINA(r)) trial, which
evaluates the effect of treatment with linagliptin versus glimepiride on
cardiovascular outcomes. CAROLINA(r) includes patients with type 2 diabetes
mellitus with sub-optimal glycaemic control at elevated cardiovascular risk. The
substudy will evaluate patients randomised and treated who have a baseline Mini
Mental State Examination (MMSE) score >= 24, documented years of formal education
with at least one valid cognitive assessment at baseline and during follow-up.
The primary cognitive outcome is the occurrence of accelerated cognitive decline
at the end of follow-up. The two treatment groups will be compared by using a
logistic regression. Accelerated cognitive decline is defined as a rate of
cognitive decline that falls at or below the 16th percentile of decline for the
whole cohort on either the MMSE or a combined score of the trail making and
verbal fluency test. Potential confounders are taken into account at an
individual patient level, using a regression based index. DISCUSSION: Between
December 2010 and December 2012, 6042 patients were randomised and treated with
either linagliptin (5 mg) or glimepiride (1-4 mg) once daily in CAROLINA(r).
Cognitive tests were conducted in nearly 4500 participants at baseline and are
scheduled for two subsequent assessments, after 160 weeks of follow-up and end of
follow-up. This substudy of the ongoing CAROLINA(r) trial will establish if
linagliptin is superior to glimepiride in the prevention of accelerated cognitive
decline in patients with type 2 diabetes mellitus. Final results are expected in
2019. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT 01243424 .
PMID- 29334907
TI - Hemodynamic effects of lateral tilt before and after spinal anesthesia during
cesarean delivery: an observational study.
AB - BACKGROUND: Post-spinal hypotension is a common maternal complication during
cesarean delivery. Aortocaval compression by the gravid uterus has been assumed
as a precipitating factor for post-spinal hypotension. The role of left lateral
tilting position in improving maternal cardiac output after subarachnoid block
(SAB) is unclear. The aim of this work is to investigate the effect of left
lateral tilting on maternal hemodynamics after SAB. METHODS: A prospective
observational study was conducted including 105 full term pregnant women
scheduled for cesarean delivery. Mean arterial pressure, heart rate, cardiac
output (measured by electrical cardiometry), stroke volume, and systemic vascular
resistance were recorded in three positions (supine, 150, and 300 left lateral
positions) before SAB, after SAB, and after delivery of the fetus. RESULTS:
Before SAB, no significant hemodynamic changes were reported with left lateral
tilting. A significant decrease was reported in mean arterial pressure, cardiac
output, stroke volume, and systemic vascular resistance after SAB (in supine
position). When performing left lateral tilting, there was an increase in cardiac
output, heart rate, and mean arterial pressure. No difference was reported
between the two tilt angles (150 and 300). CONCLUSIONS: Changing position of full
term pregnant woman after SAB from supine to left lateral tilted position results
increased cardiac output and mean arterial pressure. There is no difference
between the two tilt angles (150 and 300). TRIAL REGISTRATION: clinicaltrials.gov
( NCT02828176 ) retrospectively registered.
PMID- 29334908
TI - Self-reported genital warts among sexually-active university students: a cross
sectional study.
AB - BACKGROUND: Genital warts are one of the most common forms of sexually
transmitted disease, but their epidemiology has yet to be thoroughly elucidated.
The present study was designed to shed light on the prevalence of clinically
confirmed, self-reported genital warts (GWs) in a representative sample of the
university population. METHODS: In 2015, a cross-sectional survey was conducted
on 11,096 individuals approached at the Students Information Bureau where they
came to enroll for a university degree course. Participants completed an
anonymous, self-administered questionnaire providing information on their
sociodemographic characteristics, sexual behavior, and any history of clinically
diagnosed genital warts. Multivariate logistic regression was then used to
identify any factors associated with the disease. RESULTS: Our analysis was
conducted on 9259 questionnaires (83.4%). Participants were a mean 21.8 +/- 4.8
years of age, and 59.6% were female. Overall, 124 individuals (1.3%, 95%CI: 1.0
1.6) reported having been diagnosed with genital warts: 48 men (1.3%, 95%CI: 0.9
1.6), and 76 women (1.4% 95%CI: 1.1-1.7). Overall, 22.5% of the sample were
vaccinated (1.3% of the males and 36.8% of the females). The group of respondents
aged 30 years or more had the highest incidence of genital warts (males: 5.6%,
95%CI: 2.5-8.6; females: 6.9%, 95%CI: 3.4-10.4). The independent risk factors
associated with a history of disease were (for both genders) a history of other
sexually-transmitted diseases, and >=2 sex partners in the previous 24 months. A
protective role emerged for routine condom use. Additional risk factors
associated with genital warts in males concerned men who have sex with men,
bisexuality vis-a-vis heterosexuality, and smoking. CONCLUSIONS: The findings
emerging from our study help to further clarify the epidemiology of genital warts
in young people, and may be useful to public health decision-makers. This study
showed that genital warts occur in men as well as women, and suggests that both
genders should be monitored for this disease to ascertain the effects of the free
HPV vaccination offered to all girls in the Veneto in their 12th year of life
since 2008, and to all boys of the same age since 2015.
PMID- 29334909
TI - Long term unemployment, income, poverty, and social public expenditure, and their
relationship with self-perceived health in Spain (2007-2011).
AB - BACKGROUND: There is scant research that simultaneously analyzes the joint
effects of long-term unemployment, poverty and public expenditure policies on
poorer self-perceived health during the financial crisis. The aim of the study is
to analyze the joint relationship between long-term unemployment, social
deprivation, and regional social public expenditure on one side, and self
perceived health in Spain (2007-2011) on the other. METHODS: Longitudinal data
were extracted from the Survey on Living Conditions, 2007-2010 and 2008-2011
(9105 individuals and 36,420 observations), which were then used to estimate
several random group effects in the constant multilevel logistic longitudinal
models (level 1: year; level 2: individual; level 3: region). The dependent
variable was self-perceived health. Individual independent interest variables
were long and very long term unemployment, available income, severe material
deprivation and regional variables were per capita expenditure on essential
public services and per capita health care expenditure. RESULTS: All of the
estimated models show a robust association between bad perceived health and the
variables of interest. When compared to employed individuals, long term
unemployment increases the odds of reporting bad health by 22% to 67%; very long
term unemployment (24 to 48 months) increases the odds by 54% to 132%. Family
income reduces the odds of reporting bad health by 16% to 28% for each additional
percentage point in income. Being a member of a household with severe material
deprivation increases the odds of perceiving one's health as bad by between 70%
and 140%. Regionally, per capita expenditure on essential public services
increases the odds of reporting good health, although the effect of this
association was limited. CONCLUSIONS: Long and very long term unemployment,
available income and poverty were associated to self-perceived bad health in
Spain during the financial crisis. Regional expenditure on fundamental public
services is also associated to poor self-perceived health, although in a more
limited fashion. Results suggest the positive role in health of active employment
and redistributing income policies.
PMID- 29334910
TI - Treatment selection of early stage non-small cell lung cancer: the role of the
patient in clinical decision making.
AB - BACKGROUND: The objective of this study is to investigate the role and experience
of early stage non-small cell lung cancer (NSCLC) patient in decision making
process concerning treatment selection in the current clinical practice. METHODS:
Stage I-II NSCLC patients (surgery 55 patients, SBRT 29 patients, median age 68)
were included in this prospective study and completed a questionnaire that
explored: (1) perceived patient knowledge of the advantages and disadvantages of
the treatment options, (2) experience with current clinical decision making, and
(3) the information that the patient reported to have received from their
treating physician. This was assessed by multiple-choice, 1-5 Likert Scale, and
open questions. The Decisional Conflict Scale was used to assess the decisional
conflict. Health related quality of life (HRQoL) was measured with SF-36
questionnaire. RESULTS: In 19% of patients, there was self-reported perceived
lack of knowledge about the advantages and disadvantages of the treatment
options. Seventy-four percent of patients felt that they were sufficiently
involved in decision-making by their physician, and 81% found it important to be
involved in decision making. Forty percent experienced decisional conflict, and
one-in-five patients to such an extent that it made them feel unsure about the
decision. Subscores with regard to feeling uninformed and on uncertainty,
contributed the most to decisional conflict, as 36% felt uninformed and 17% of
patients were not satisfied with their decision. HRQoL was not influenced by
patient experience with decision-making or patient preferences for shared
decision making. CONCLUSIONS: Dutch early-stage NSCLC patients find it important
to be involved in treatment decision making. Yet a substantial proportion
experiences decisional conflict and feels uninformed. Better patient information
and/or involvement in treatment-decision-making is needed in order to improve
patient knowledge and hopefully reduce decisional conflict.
PMID- 29334912
TI - Estimating the total prevalence and incidence of end-stage kidney disease among
Aboriginal and non-Aboriginal populations in the Northern Territory of Australia,
using multiple data sources.
AB - BACKGROUND: Most estimates for End Stage Kidney Disease (ESKD) prevalence and
incidence are based on renal replacement therapy (RRT) registers. However, not
all people with ESKD will commence RRT and estimates based only on RRT registry
data will underestimate the true burden of ESKD in the community. This study
estimates the total number of Northern Territory (NT) residents with ESKD
including: those receiving RRT, those diagnosed but not receiving RRT and an
estimate of "undiagnosed" cases. METHODS: Four data sources were used to identify
NT residents with a diagnosis of ESKD: public hospital admissions, Australia and
New Zealand Dialysis and Transplant Registry registrations, death registrations
and, for the Aboriginal population only, electronic primary care records. Three
data sources contained information recorded between 1 July 2008 and 31 December
2013, death registration data extended to 31 December 2014 to capture 2013
prevalent cases. A capture-recapture method was used to estimate both diagnosed
and undiagnosed cases by making use of probability patterns of overlapping
multiple data sources. RESULTS: In 2013, the estimated ESKD prevalence in the NT
Aboriginal population was 11.01 (95% confidence interval (CI) 10.24-11.78) per
1000, and 0.90 (95% CI 0.76-1.05) per 1000 in the NT non-Aboriginal population.
The age-adjusted rates were 17.97 (95% CI 17.82-18.11) and 1.07 (95% CI 1.05
1.09) per 1000 in the NT Aboriginal and non-Aboriginal populations respectively.
The proportion of individuals receiving RRT was 71.4% of Aboriginal and 75.5% of
non-Aboriginal prevalent ESKD cases. The age-adjusted ESKD incidence was also
greater for the Aboriginal (5.26 (95% CI 4.44-6.08) per 1000 population) than non
Aboriginal population (0.36 (95% CI 0.25-0.47) per 1000). CONCLUSION: This study
provides comprehensive estimates of the burden of ESKD including those cases that
are not identified in relevant health data sources. The results are important for
informing strategies to reduce the total burden of ESKD and to manage the
potential unmet demand, particularly from comparatively young Aboriginal patients
who may be suitable for RRT but do not currently access the services for social,
geographic or cultural reasons.
PMID- 29334911
TI - Hypocholesterolemia is an independent risk factor for depression disorder and
suicide attempt in Northern Mexican population.
AB - BACKGROUND: Cholesterol has been associated as a risk factor for cardiovascular
disease. Recently, however, there is growing evidence about crucial requirement
of neuron membrane cholesterol in the organization and function of the 5-HT1A
serotonin receptor. For this, low cholesterol level has been reported to be
associated with depression and suicidality. However there have been inconsistent
reports about this finding and the exact relationship between these factors
remains controversial. Therefore, we investigated the link between serum
cholesterol and its fractions with depression disorder and suicide attempt in 467
adult subjects in Mexican mestizo population. METHODS: Plasma levels of total
cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-c) and
low density lipoprotein cholesterol (LDL-c) were determined in 261 MDD patients
meeting the DSM-5 criteria for major depressive disorder (MDD), 59 of whom had
undergone an episode of suicide attempt, and 206 healthy controls. RESULTS: A
significant decrease in total cholesterol, LDL-cholesterol, VLDL-cholesterol and
triglyceride serum levels was observed in the groups of MDD patients and suicide
attempt compared to those without suicidal behavior (p < 0.05). After adjusting
for covariates, lower cholesterol levels were significantly associated with MDD
(OR 4.229 CI 95% 2.555 - 7.000, p<.001) and suicide attempt (OR 5.540 CI 95%
2.825 - 10.866, p<.001) CONCLUSIONS: These results support the hypothesis that
lower levels of cholesterol are associated with mood disorders like MDD and
suicidal behavior. More mechanistic studies are needed to further explain this
association.
PMID- 29334913
TI - Identifying enablers and barriers to individually tailored prescribing: a survey
of healthcare professionals in the UK.
AB - BACKGROUND: Many people now take multiple medications on a long-term basis to
manage health conditions. Optimising the benefit of such polypharmacy requires
tailoring of medicines use to the needs and circumstances of individuals.
However, professionals report barriers to achieving this in practice. In this
study, we examined health professionals' perceptions of enablers and barriers to
delivering individually tailored prescribing. METHODS: Normalisation Process
Theory (NPT) informed an on-line survey of health professionals' views of
enablers and barriers to implementation of Individually Tailored Prescribing
(ITP) of medicines. Links to the survey were sent out through known professional
networks using a convenience/snowball sampling approach. Survey questions sought
to identify perceptions of supports/barriers for ITP within the four domains of
work described by NPT: sense making, engagement, action and monitoring. Analysis
followed the framework approach developed in our previous work. RESULTS: Four
hundred and nineteen responses were included in the final analysis (67.3% female,
32.7% male; 52.7% nurse prescribers, 19.8% pharmacists and 21.8% GPs). Almost
half (44.9%) were experienced practitioners (16+ years in practice); around one
third reported already routinely offering ITP to their patients. GPs were the
group least likely to recognise this as consistent usual practice. Findings
revealed general support for the principles of ITP but significant variation and
inconsistency in understanding and implementation in practice. Our findings
reveal four key implications for practice: the need to raise understanding of ITP
as a legitimate part of professional practice; to prioritise the work of ITP
within the range of individual professional activity; to improve the consistency
of training and support for interpretive practice; and to review the impact of
formal and informal monitoring processes on practice. CONCLUSION: The findings
will inform the ongoing development of our new complex intervention (PRIME
Prescribing) to support the individual tailoring of medicines needed to address
problematic polypharmacy.
PMID- 29334914
TI - "Crying without tears" as an early diagnostic sign-post of triple A (Allgrove)
syndrome: two case reports.
AB - BACKGROUND: Triple A syndrome (or Allgrove syndrome) is a rare autosomal
recessive disorder characterized by alacrima, achalasia, adrenal insufficiency
and autonomic/neurological abnormalities. The majority of cases are caused by
mutations in the AAAS gene located on chromosome 12q13. However, the clinical
picture as well as genetic testing may be complex since symptomatology is
variable and mutations cannot be identified in all clinically diagnosed patients.
We present two unrelated patients with triple-A syndrome illustrating the
importance of alacrima as an early clinical sign. CASE PRESENTATION: A 3.5 year
old girl presented with repeated hypoglycaemic myoclonic events. Adrenal
insufficiency was diagnosed. In addition, alacrima, obvious since early infancy,
was incidentally reported by the mother and finally lead to the clinical
diagnosis of triple A syndrome. This was confirmed by positive mutation analysis
of the AAAS gene. The second patient, an 8 months old boy was presented because
of anisocoria and unilateral optic atrophy. MRI revealed cerebellar vermis
hypotrophy. Psychomotor retardation, failure to thrive, and frequent vomiting
lead to further diagnostic work-up. Achalasia was diagnosed radiologically. In
addition, the mother mentioned absence of tears since birth leading to the
clinical diagnosis of triple A syndrome. In contrast to the first cases genetic
testing was negative. CONCLUSION: These two patients illustrate the heterogeneity
of triple A syndrome in both terms, clinical expression and genetic testing. We
particularly aim to stress the importance of alacrima, which should be considered
as a red flag symptom. Further differential diagnosis is required in every child
affected by alacrima.
PMID- 29334916
TI - Influence of drought stress on afalfa yields and nutritional composition.
AB - BACKGROUND: It is predicted that climate change may increase the risk of local
droughts, with severe consequences for agricultural practices. METHODS: Here we
report the influence of drought on alfalfa yields and nutritional composition,
based on artificially induced drought conditions during two field experiments.
Two types of alfalfa cultivars were compared, Gold Queen and Suntory. The
severity and timing of drought periods were varied, and the crop was harvested
either early during flowering, or late at full bloom. RESULTS: The obtained dry
mass yields of Gold Queen were higher than Suntory, and the first was also more
resistant to drought. Early harvest resulted in higher yields. Decreases in
yields due to water shortage were observed with both cultivars, and the fraction
of crude protein (CP) decreased as a result of drought stress; this fraction was
higher in Gold Queen than in Suntory and higher in early harvest compared to late
harvest. Severe drought late in spring had the highest effect on CP content. The
fraction of fibre, split up into neutral detergent fibre (NDF) and acid detergent
fibre (ADF) increased as a result of drought and was lower in early compared to
late harvested plants. Suntory alfalfa produced higher fibre fractions than Gold
Queen. The fraction of water-soluble carbohydrates (WSC) was least affected by
drought. It was consistently higher in Gold Queen compared to Suntory alfalfa,
and late harvest resulted in higher WSC content. CONCLUSIONS: In combination,
these results suggest that the nutritive value of alfalfa will likely decrease
after a period of drought. These effects can be partly overcome by choosing the
Gold Queen cultivar over Suntory, by targeted irrigation, in particular in late
spring, and by harvesting at an earlier time.
PMID- 29334915
TI - Monitoring the responsiveness of T and antigen presenting cell compartments in
breast cancer patients is useful to predict clinical tumor response to
neoadjuvant chemotherapy.
AB - BACKGROUND: Vaccination of mice with tumors treated with Doxorubicin promotes a T
cell immunity that relies on dendritic cell (DC) activation and is responsible
for tumor control in vaccinated animals. Despite Doxorubicin in combination with
Cyclophosphamide (A/C) is widely used to treat breast cancer patients, the
stimulating effect of A/C on T and APC compartments and its correlation with
patient's clinical response remains to be proved. METHODS: In this prospective
study, we designed an in vitro system to monitor various immunological readouts
in PBMCs obtained from a total of 17 breast cancer patients before, and after
neoadjuvant anti-tumor therapy with A/C. RESULTS: The results show that before
treatment, T cells and DCs, exhibit a marked unresponsiveness to in vitro
stimulus: whereas T cells exhibit poor TCR internalization and limited expression
of CD154 in response to anti-CD3/CD28/CD2 stimulation, DCs secrete low levels of
IL-12p70 and limited CD83 expression in response to pro-inflammatory cytokines.
Notably, after treatment the responsiveness of T and APC compartments was
recovered, and furthermore, this recovery correlated with patients' residual
cancer burden stage. CONCLUSIONS: Our results let us to argue that the model used
here to monitor the T and APC compartments is suitable to survey the recovery of
immune surveillance and to predict tumor response during A/C chemotherapy.
PMID- 29334917
TI - Obesity and breast cancer outcomes in chemotherapy patients in New Zealand - a
population-based cohort study.
AB - BACKGROUND: Obesity has been reported as an adverse prognostic factor in breast
cancer, but inconsistently, and under-treatment with chemotherapy may occur. We
provide the first assessment of obesity and breast cancer outcomes in a
population-based, multi-ethnic cohort of New Zealand patients treated with
chemotherapy. METHODS: All 3536 women diagnosed with invasive breast cancer in
the Waikato region of New Zealand from 2000-2014 were registered and followed
until last follow-up in specialist or primary care, death or Dec 2014; median
follow-up 4.1 years. For the 1049 patients receiving chemotherapy, mortality from
breast cancer, other causes, and all causes, and rates of loco-regional and of
distant recurrence, were assessed by body mass index (BMI), recorded after
diagnosis, adjusting for other clinico-pathological and demographic factors by
Cox regression. RESULTS: BMI was known for 98% (n=1049); 33% were overweight (BMI
25-29.9), 21% were obese (BMI 30-34.9), and 14% were very obese (BMI 35+). There
were no significant associations between obesity and survival, after adjustment
for demographic and clinical factors (hazard ratios, HR, for very obese compared
to BMI 21-24, for breast cancer deaths 0.96 (0.56-1.67), and for all deaths 1.03
(0.63-1.67), respectively, and only small non-significant associations for loco
regional or metastatic recurrence rates (HR 1.17 and 1.33 respectively). Subgroup
analyses by age, menopausal status, ethnicity, stage, post-surgical radiotherapy,
mode of diagnosis, type of surgery, and receptor status, showed no associations.
No associations were seen with BMI as a continuous variable. The results in all
patients irrespective of treatment but with recorded BMI data (n=2296) showed
similar results. CONCLUSIONS: In this population, obesity assessed post-diagnosis
had no effect on survival or recurrence, based on 1049 patients with chemotherapy
treatment with follow-up up to 14 years.
PMID- 29334919
TI - Low birthweight in rural Cameroon: an analysis of a cut-off value.
AB - BACKGROUND: Low birthweight (LBW) is a major predictor of early neonatal
mortality which disproportionately affects low-income countries. WHO recommends
regional definitions for LBW to prevent misclassifications and ensure appropriate
care of babies with LBW. We conducted this study to define a clinical cut-off for
LBW, and to determine the predictors and adverse foetal outcomes of LBW babies in
a rural sub-division in Cameroon. METHODS: We conducted a retrospective register
analysis of 1787 singleton deliveries in two health facilities in the Northwest
Region of Cameroon. Records with no birthweight or birthweight less than 1000 g,
babies born before arrival, multiple deliveries and deliveries before 28 weeks
gestation were excluded from this study. The 10th percentile of birthweights was
computed to obtain a statistical cut-off value for the LBW. To assess the
clinical significance of the newly defined cut-off value, we compared the
prevalence of adverse foetal outcomes between LBW (birthweight <10th percentile)
and heavier babies (birthweight >=10th percentile) in our study population.
RESULTS: The 10th percentile of the birthweights was 2700 g. Preterm delivery was
the lone predictor of LBW (aOR = 2.0, 95% CI = 1.3-3.1; p = 0.001). LBW babies
were more likely to be stillborn (OR = 9.6; 95% CI = 4.2-21.6; p < 0.001) or
asphyxiated at the 5th minute (OR = 2.0; 95% CI = 1.2-3.3; p = 0.006), compared
with heavier babies. Also, 6.1% of babies who had a birthweight between 2500 and
2700 g were more likely to be stillborn compared to heavier babies. CONCLUSION:
This study suggests that the clinical cut-off for LBW in this rural community is
2700 g; with 6.1% of babies born with LBW probably receiving inadequate care as
the traditional cut-off value of 2500 g proposed by WHO is still used to define
LBW in our setting. Further studies are necessary to define a national cut-off
value for harmonisation of LBW definitions in the country to prevent
misclassifications and ensure appropriate neonatal care.
PMID- 29334918
TI - Colorectal cancer liver metastases - a population-based study on incidence,
management and survival.
AB - BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer-associated
deaths with liver metastases developing in 25-30% of those affected. Previous
data suggest a survival difference between right- and left-sided liver metastatic
CRC, even though left-sided cancer has a higher incidence of liver metastases.
The aim of the study was to describe the liver metastatic patterns and survival
as a function of the characteristics of the primary tumour and different
combinations of metastatic disease. METHODS: A retrospective population-based
study was performed on a cohort of patients diagnosed with CRC in the region of
Stockholm, Sweden during 2008. Patients were identified through the Swedish
National Quality Registry for Colorectal Cancer Treatment (SCRCR) and additional
information on intra- and extra-hepatic metastatic pattern and treatment were
retrieved from electronic patient records. Patients were followed for 5 years or
until death. Factors influencing overall survival (OS) were investigated by means
of Cox regression. OS was compared using Kaplan-Meier estimations and the log
rank test. RESULTS: Liver metastases were diagnosed in 272/1026 (26.5%) patients
within five years of diagnosis of the primary. Liver and lung metastases were
more often diagnosed in left-sided colon cancer compared to right-sided cancer
(28.4% versus 22.1%, p = 0.029 and 19.7% versus 13.2%, p = 0.010, respectively)
but the extent of liver metastases were more extensive for right-sided cancer as
compared to left-sided (p = 0.001). Liver metastatic left-sided cancer, including
rectal cancer, was associated with a 44% decreased mortality risk compared to
right-sided cancer (HR = 0.56, 95% CI: 0.39-0.79) with a 5-year OS of 16.6%
versus 4.3% (p < 0.001). In liver metastatic CRC, the presence of lung metastases
did not significantly influence OS as assessed by multivariate analysis (HR =
1.11, 95% CI: 0.80-1.53). CONCLUSION: The worse survival in liver metastatic
right-sided colon cancer could possibly be explained by the higher number of
metastases, as well as more extensive segmental involvement compared with left
sided colon and rectal cancer, even though the latter had a higher incidence of
liver metastases. Detailed population-based data on the metastatic pattern of CRC
and survival could assist in more structured and individualized guidelines for
follow-up of patients with CRC.
PMID- 29334920
TI - Factors influencing access of pregnant women and their infants to their local
healthcare system: a prospective, multi-centre, observational study.
AB - BACKGROUND: The successful implementation of maternal vaccination relies on
results of clinical trials, considering the prenatal and postnatal attendance at
selected healthcare institutions. This study evaluated factors influencing
maternal/infant access to healthcare facilities to identify potential barriers to
participation in future clinical trials on maternal vaccination. METHODS: In this
prospective, multi-centre, observational study, pregnant women (N = 3243) were
enrolled at ten sites across Panama, the Dominican Republic, South Africa, and
Mozambique between 2012 and 2014. They completed questionnaires at enrolment,
delivery, and infant follow-up (90 days post-partum) visits, including questions
on transportation, phone accessibility, alternative childcare, gestational age at
enrolment, delivery location, and health status of their infant. Logistic
regression was used to identify factors significantly associated with return to
study site for delivery or infant follow-up visits. RESULTS: Among 3229 enrolled
women with delivery information, 63.6% (range across sites: 25.3-91.5%) returned
to study site for delivery. Older women and those at later gestational age at
enrolment were more likely to deliver at the study site. While heterogeneities
were observed at site level, shorter travel time at delivery and increased
transportation costs at enrolment were associated with increased likelihood of
women returning to study site for delivery. Among 3145 women with live-born
infants, 3077 (95.3%) provided 90-day follow-up information; of these, 68.9%
(range across sites: 25.6-98.9%) returned to study site for follow-up visits.
Women with other children and with lower transportation costs at delivery were
more likely to return to study site for follow-up visits. Among 666 infants
reported sick, 94.3% were taken to a healthcare facility, with only 41.9% (range
across sites: 4.9-77.3%) to the study site. CONCLUSION: Although high retention
was observed from enrolment through 90 days after delivery, post-partum
surveillance should be broadened beyond the study sites and additional follow-up
visits should be planned within the neonatal period. The factors influencing
maternal/infant access to healthcare facilities and the issues identified in this
study should be taken into consideration in planning future clinical studies on
maternal immunisation in low- and middle-income countries. TRIAL REGISTRATION:
The study was registered at ClinicalTrial.gov ( NCT01734434 ) on November 22,
2012.
PMID- 29334921
TI - A pilot feasibility randomised controlled trial of an adjunct brief social
network intervention in opiate substitution treatment services.
AB - BACKGROUND: Approximately 3% of people receiving opioid substitution therapy
(OST) in the UK manage to achieve abstinence from prescribed and illicit drugs
within three years of commencing treatment. Involvement of families and wider
social networks in supporting psychological treatment may be an effective
strategy in facilitating recovery, and this pilot study aimed to evaluate the
impact of a social network-focused intervention for patients receiving OST.
METHODS: A two-site, open feasibility trial randomised patients receiving OST for
at least 12 months but still reporting illicit opiate use in the past 28 days to
one of three treatments: 1) treatment as usual (TAU), 2) Brief Social Behaviour
and Network Therapy (B-SBNT) + TAU, or 3) Personal Goal Setting (PGS) + TAU. The
two active interventions consisted of 4 sessions. There were 3 aims: 1) test the
feasibility of recruiting OST patients to a trial of B-SBNT, and following them
up over 12 months; 2) test the feasibility of training clinicians to deliver B
SBNT; 3) test whether B-SBNT reduces heroin use 3 and 12 months after treatment,
and to explore potential mediating factors. The primary outcome for aim 3 was
number of days of heroin use in the past month, and a range of secondary outcome
measures were specified in advance (level of drug dependence, mental health,
social satisfaction, therapist rapport, treatment satisfaction, social network
size and support). RESULTS: A total of 83 participants were randomised, and 70
(84%) were followed-up at 12 months. Fidelity analysis of showed that B-SBNT
sessions were clearly distinguishable from PGS and TAU sessions, suggesting it
was possible to train clinical staff to an adequate level of competence. No
significant differences were found between the 3 intervention arms in the primary
or secondary outcome measures. Attendance at psychosocial treatment intervention
sessions was low across all three arms (44% overall). CONCLUSIONS: Patients
receiving OST can be recruited into a trial of a social network-based
intervention, but poor attendance at treatment sessions makes it uncertain
whether an adequate dose of treatment was delivered. In order to achieve the
benefits of psychosocial interventions, further work is needed to overcome poor
engagement. TRIAL REGISTRATION: ISRCTN Trial Registration Number: ISRCTN22608399
. Date of registration: 27/04/2012. Date of first randomisation: 14/08/2012.
PMID- 29334922
TI - Relative contribution of various chronic diseases and multi-morbidity to
potential disability among Dutch elderly.
AB - BACKGROUND: The amount of time spent living with disease greatly influences
elderly people's wellbeing, disability and healthcare costs, but differs by
disease, age and sex. METHODS: We assessed how various single and combined
diseases differentially affect life years spent living with disease in Dutch
elderly men and women (65+) over their remaining life course. Multistate life
table calculations were applied to age and sex-specific disease prevalence,
incidence and death rates for the Netherlands in 2007. We distinguished
congestive heart failure, coronary heart disease (CHD), breast and prostate
cancer, colon cancer, lung cancer, diabetes, COPD, stroke, dementia and
osteoarthritis. RESULTS: Across ages 65, 70, 75, 80 and 85, CHD caused the most
time spent living with disease for Dutch men (from 7.6 years at age 65 to 3.7
years at age 85) and osteoarthritis for Dutch women (from 11.7 years at age 65 to
4.8 years at age 85). Of the various co-occurrences of disease, the combination
of diabetes and osteoarthritis led to the most time spent living with disease,
for both men (from 11.2 years at age 65 to 4.9 -years at age 85) and women (from
14.2 years at age 65 to 6.0 years at age 85). CONCLUSIONS: Specific single and
multi-morbid diseases affect men and women differently at different phases in the
life course in terms of the time spent living with disease, and consequently,
their potential disability. Timely sex and age-specific interventions targeting
prevention of the single and combined diseases identified could reduce healthcare
costs and increase wellbeing in elderly people.
PMID- 29334923
TI - Relationship between corneal biomechanical properties and structural biomarkers
in patients with normal-tension glaucoma: a retrospective study.
AB - BACKGROUND: We evaluated the relationships between corneal biomechanical
properties and structural parameters in patients with newly diagnosed, untreated
normal-tension glaucoma (NTG). METHODS: All subjects were evaluated using an
Ocular Response Analyzer (ORA) measuring corneal hysteresis (CH) and the corneal
resistance factor (CRF). Central corneal thickness (CCT), Goldmann applanation
tonometric (GAT) data, axial length, and the spherical equivalent (SE), were also
measured. Confocal scanning laser ophthalmoscopy was performed with the aid of a
Heidelberg retina tomograph (HRT III). We sought correlations between HRT
parameters and different variables including CCT, CH, and the CRF. Multiple
linear regression analysis was performed to identify significant associations
between corneal biomechanical properties and optic nerve head parameters.
RESULTS: We enrolled 95 eyes of 95 NTG patients and 93 eyes of 93 normal
subjects. CH and the CRF were significantly lower in more advanced glaucomatous
eyes (P = 0.001, P = 0.008, respectively). The rim area, rim volume, linear cup
to-disc ratio (LCDR), and mean retinal nerve fiber layer (RNFL) thickness were
significantly worse in more advanced glaucomatous eyes (P < 0.001, P < 0.001, P <
0.001, and P = 0.001). CH was directly associated with rim area, rim volume, and
mean RNFL thickness (P = 0.012, P = 0.028, and P = 0.043) and inversely
associated with LCDR (P = 0.015), after adjusting for age, axial length, CCT,
disc area, GAT data, and SE. However, in normal subjects, there were no
significant associations between corneal biomechanical properties and HRT
parameters. CONCLUSIONS: A lower CH is significantly associated with a smaller
rim area and volume, a thinner RNFL, and a larger LCDR, independent of disc size,
corneal thickness, intraocular pressure, and age.
PMID- 29334924
TI - Longitudinal observation of subretinal fibrosis in Vogt-Koyanagi-Harada disease.
AB - BACKGROUND: Subretinal fibrosis (SRF) is a vision-threatening complication of
Vogt-Koyanagi-Harada disease (VKH). It has long been recognized as a sequela of
chronic inflammation. The developmental process of SRF, however, has not been
described. The purpose of this study is to provide longitudinal observations of
SRF in VKH. METHODS: Retrospective chart review of 10 VKH patients referred to
our group between January 2008 and September 2015 at acute uveitic stage with SRF
at presentation or who developed SRF during follow up. RESULTS: Ten patients (6
males and 4 females) with a median age of 39.0 (range, 23 to 58) years old were
included. The median disease duration at presentation and median duration of
follow up were 25.5 (range 5 to 60) days and 32.5 (range 13 to 61) months
respectively. At presentation, all patients except one had been inappropriately
treated with glucocorticosteroid (insufficiently dosed or tapered too fast) for
longer than 2 weeks. Despite large dose oral glucocorticosteroid (1 mg/kg/d
prednisone or equivalent) with slow tapering in combination with at least one
immunomodulatory agent (cyclosporin A, cyclophosphamide or azathioprine) after
presentation, all patients developed bilateral SRF within the first 4 months of
disease course and 7 patients within the first 2 months. In 8 patients, shape
change/migration and progressive proliferation/pigmentation of SRF was observed
over a period of several months after its formation, and then became quiescent
but may further underwent depigmentation or pigmentation. SRF involved macula in
12 eyes (7 patients) and caused treatment resistant macular detachment and severe
visual impairment in 6 eyes (4 patients). At the last visit, eyes with macular
involvement were more common to had worse final best corrected visual acuity
(<=20/50) than those without (9/12 vs. 0/8, p = 0.001). CONCLUSIONS: SRF usually
develop early in the disease course in VKH patients who are not adequately
controlled; it usually undergoes a highly dynamic process within the subretinal
space and may involve the macula and resulted in poor final visual outcome.
PMID- 29334925
TI - Implementing blended learning in emergency airway management training: a
randomized controlled trial.
AB - BACKGROUND: While emergency airway management training is conventionally
conducted via face-to-face learning (F2FL) workshops, there are inherent cost,
time, place and manpower limitations in running such workshops. Blended learning
(BL) refers to the systematic integration of online and face-to-face learning
aimed to facilitate complex thinking skills and flexible participation at a
reduced financial, time and manpower cost. This study was conducted to evaluate
its effectiveness in emergency airway management training. METHODS: A single
center prospective randomised controlled trial involving 30 doctors from Sarawak
General Hospital, Malaysia was conducted from September 2016 to February 2017 to
compare the effectiveness of BL versus F2FL for emergency airway management
training. Participants in the BL arm were given a period of 12 days to go through
the online materials in a learning management system while those in the F2FL arm
attended a-day of face-to-face lectures (8 h). Participants from both arms then
attended a day of hands-on session consisting of simulation skills training with
airway manikins. Pre- and post-tests in knowledge and practical skills were
administered. E-learning experience and the perception towards BL among
participants in the BL arm were also assessed. RESULTS: Significant improvements
in post-test scores as compared to pre-test scores were noted for participants in
both BL and F2FL arms for knowledge, practical, and total scores. The degree of
increment between the BL group and the F2FL arms for all categories were not
significantly different (total scores: 35 marks, inter-quartile range (IQR) 15.0
41.0 vs. 31 marks, IQR 24.0 - 41.0, p = 0.690; theory scores: 18 marks, IQR 9 -
24 vs. 19 marks, IQR 15 - 20, p = 0.992; practical scores: 11 marks, IQR 5 -18
vs. 10 marks, IQR 9 - 20, p = 0.461 respectively). The overall perception towards
BL was positive. CONCLUSIONS: Blended learning is as effective as face-to-face
learning for emergency airway management training of junior doctors, suggesting
that blended learning may be a feasible alternative to face-to-face learning for
such skill training in emergency departments. TRIAL REGISTRATION: Malaysian
National Medical Research NMRR-16-696-30190 . Registered 28 April 2016.
PMID- 29334926
TI - (R)-alpha-Lipoic acid inhibits fructose-induced myoglobin fructation and the
formation of advanced glycation end products (AGEs) in vitro.
AB - BACKGROUND: Fructose-mediated protein glycation (fructation) has been linked to
an increase in diabetic and cardiovascular complications due to over consumption
of high-fructose containing diets in recent times. The objective of the present
study is to evaluate the protective effect of (R)-alpha-lipoic acid (ALA) against
fructose-induced myoglobin fructation and the formation of advanced glycation end
products (AGEs) in vitro. METHODS: The anti-glycation activity of ALA was
determined using the formation of AGEs fluorescence intensity, iron released from
the heme moiety of myoglobin and the level of fructosamine. The fructation
induced myoglobin oxidation was examined using the level of protein carbonyl
content and thiol group estimation. RESULTS: The results showed that co
incubation of myoglobin (1 mg/mL), fructose (1 M) and ALA (1, 2 and 4 mM)
significantly inhibited the formation of AGEs during the 30 day study period. ALA
markedly decreased the levels of fructosamine, which is directly associated with
the reduction of AGEs formation. Furthermore, ALA significantly reduced free iron
release from myoglobin which is attributed to the protection of myoglobin from
fructose-induced glycation. The results also demonstrated a significant
protective effect of ALA on myoglobin oxidative damages, as seen from decreased
protein carbonyl content and increased protein thiols. CONCLUSION: These findings
provide new insights into the anti-glycation properties of ALA and emphasize that
ALA supplementation is beneficial in the prevention of AGEs-mediated diabetic and
cardiovascular complications.
PMID- 29334927
TI - Dexmedetomidine prevents acute kidney injury after adult cardiac surgery: a meta
analysis of randomized controlled trials.
AB - BACKGROUND: Dexmedetomidine has been shown to confer direct renoprotection by
stabilizing the sympathetic system, exerting anti-inflammatory effects and
attenuating ischemia/reperfusion (I/R) injury in preclinical studies. Results
from clinical trials of dexmedetomidine on acute kidney injury (AKI) following
adult cardiac surgery are controversial. METHODS: We searched EMBASE, PubMed, and
Cochrane CENTRAL databases for randomized controlled trials (RCTs) comparing the
renal effect of dexmedetomidine versus placebo or other anesthetic drugs in adult
patients undergoing cardiac surgery. The primary outcome was the incidence of
AKI. The secondary outcomes were mechanical ventilation (MV) duration, intensive
care unit (ICU) stay and hospital length of stay(LOS), and postoperative
mortality (in-hospital or within 30 days). RESULTS: Ten trials with a total of
1575 study patients were selected. Compared with controls, dexmedetomidine
significantly reduced the incidence of postoperative AKI [68/788 vs 97/787; odds
ratio(OR), 0.65; 95% confidence interval (CI), 0.45-0.92; P = 0.02; I2 = 0.0%],
and there was no difference between groups in postoperative mortality (4/487 vs
11/483; OR, 0.43; 95% CI, 0.14-1.28; P = 0.13; I2 = 0.0%), MV duration [in days;
n = 1229; weighted mean difference(WMD), -0.22; 95% CI, -2.04 to 1.70; P = 0.81],
ICU stay (in days; n = 1363; WMD, -0.85; 95% CI, -2.14 to 0.45; P = 0.20), and
hospital LOS (in days; n = 878; WMD, -0.24; 95% CI, -0.71 to 0.23; P = 0.32).
CONCLUSIONS: Perioperative administration of dexmedetomidine in adult patients
undergoing cardiac surgery may reduce the incidence of postoperative AKI. Future
trials are needed to determine the dose and timing of dexmedetomidine in
improving outcomes, especially in patients with decreased baseline kidney
function.
PMID- 29334928
TI - Consumption of sweetened-beverages and poverty in Colombia: when access is not an
advantage.
AB - BACKGROUND: This study characterizes the intake of sweetened beverages and
establishes whether economic inequalities in their consumption exists. METHODS:
Ecological study. Mixed methods using food frequency questionnaire and inequality
indices. Based on the National Nutrition Survey, Colombia, 2010. The sweetened
beverage intake of 17,514 subjects in 33 geodemographic units was estimated with
a food frequency questionnaire and summarized. The calculation of inequality was
based on the monetary poverty. The prevalence (yes/no) and frequency (times/day)
of sweetened beverage consumption were estimated. Indices of economic inequality
were calculated for both prevalence and frequency. RESULTS: The prevalence of
sweetened beverage consumption was between 79.2% (95% CI, 75.7 to 82.8) in adults
and 88.5% (95% CI, 85.8 to 91.3) in minors. The frequency of consumption in terms
of times/day, was between 0.20 (95% CI, 0.16 to 0.24) in adults and 0.40 (95% CI,
0.33 to 0.46) in minors. The Gini coefficient for the prevalence was close to
zero, between 0.04 and 0.08; for the frequency, it was slightly higher, between
0.12 and 0.25. CONCLUSIONS: It was established that there is no economic
inequality in the consumption of sweetened beverages. Consumption taxes could be
regressive.
PMID- 29334929
TI - Chronic kidney disease in sugarcane workers in Cameroon: a cross-sectional study.
AB - BACKGROUND: Agricultural workers especially in sugarcane plantations have a high
risk of chronic kidney disease (CKD). Little is known about CKD among sugarcane
plantation workers in Cameroon. This study sought to evaluate the prevalence and
identify factors associated with CKD in sugarcane plantation workers in Cameroon.
METHODS: We conducted an analytic cross-sectional study including 204 adult
workers at the sugarcane plantation complex in Mbandjock, Cameroon; over 500 m
above sea level. Chronic kidney disease (proteinuria as estimated by urine
dipstick analysis and/or estimated glomerular filtration rate < 60 ml/min/1.73 m2
persistent after 3 months) was the outcome of interest. Those with abnormal
results were seen again after 3 months to confirm the diagnosis. We evaluated the
association between CKD and participant age, sex, contract-type, duration of
employment, socio-economic status, workspace, exposure to agrochemicals, heavy
metals and heat, selected risk factors and co-morbid conditions. RESULTS: The
overall prevalence of CKD was 3.4%. The factory workers were the most affected
(7%), compared to the field (2.4%) and office workers (0%). 2.9% of the
participants had persistent proteinuria, mild in every case, and 0.5% of them had
an estimated glomerular filtration rate < 60 ml/min/1.73 m2. Age >= 40 years was
an independent predictor of CKD. CONCLUSION: The prevalence of CKD among
employees of the Mbandjock sugarcane plantation is low, probably reflecting the
preventive measures against heat stress and dehydration in place.
PMID- 29334930
TI - Safety and adequacy of percutaneous kidney biopsy performed by nephrology
trainees.
AB - BACKGROUND: Recently there has been a progressive loss of specialty related
skills for nephrologists. Among the skills we find the kidney biopsy that has a
central role in diagnosis of renal parenchymal disease. One of the causes might
be the belief that the kidney biopsy should be performed only in larger Centers
which can rely on the presence of a renal pathologist and on nephrologists with a
large experience. This trend may increase in the short term procedural safety but
may limit the chance of in training nephrologists to become confident with the
technique. METHODS: We evaluated renal biopsies performed from May 2002 to
October 2016 in our Hospital, a mid-sized facility to determine whether the
occurrence of complications would be comparable to those reported in literature
and whether the increase in the number of biopsy performing physicians including
nephrology fellows which took place since January 2012, after our Nephrology Unit
became academic, would be associated to an increase of complications or a
reduction of diagnostic power of renal biopsies. Three hundred thirty seven
biopsies were evaluated. Patients underwent ultrasound guided percutaneous renal
biopsy using a 14 G core needle loaded on a biopsy gun. Observation lasted for 24
h, we evaluated hemoglobin levels 6 and 24 h and kidney ultrasound 24 h after the
biopsy. RESULTS: Complications occurred in 18.7% of patients, of these only 1,2%
were major complications. Complications were more common in female (28%) compared
to male patients (14,8%) (p = 0.004). We found no correlation between diagnosis,
kidney function and complication rates; hypertension was not associated to a
higher risk in complications. The increase of biopsy performing personnel was not
associated to an increase in complication rates (18,7% both pre and post 2012) or
with an increase of major complications (1.2% vs 1,2%). CONCLUSIONS: Kidney
biopsy can be safely performed in mid-sized hospitals. Safety and adequacy are
guaranteed even if the procedure is performed by a larger number of less
experienced nephrologists as long as under tutor supervision, thus kidney biopsy
should become an integral part of a nephrology fellow training allowing more
widespread diffusion of this technique.
PMID- 29334931
TI - In vitro antibacterial and antibiotic modifying activity of crude extract,
fractions and 3',4',7-trihydroxyflavone from Myristica fragrans Houtt against MDR
Gram-negative enteric bacteria.
AB - BACKGROUND: Nutmeg is the seed kernel inside the fruit of Myristica fragrans
Houtt. (Myristicaceae). It possesses various pharmacological activities but is
used in Cameroon only for its flavor in making cakes. The present study thus
aimed to investigate the in vitro antibacterial activity and antibiotic modifying
activities of crude seed kernel methanol extract (MFS), fractions (MFSa-e) as
well as 3',4',7-trihydroxyflavone from Myristica fragrans against a panel of
multi-drug resistant (MDR) Gram-negative bacteria. METHODS: The modified rapid p
iodonitrotetrazolium chloride (INT) colorimetric assay was used to determine the
Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration
(MBC) on the tested bacteria, as well as those of antibiotics in association with
the extract and/or isolated compound. Column chromatography was used for the
fractionation and purification of the seed kernel extract whilst the chemical
structures of compounds were determined using spectroscopic techniques. RESULTS:
Phytochemical investigations lead to the isolation of 3',4',7-trihydroxyflavone
from the fraction MFSb. The crude extract showed antibacterial activity with MICs
ranging from 32 to 1024 MUg/mL on the majority of the 29 tested Gram-negative
bacterial strains. Fraction MFSb inhibited the growth of 100% (29/29) of the
tested bacterial strains, as well as the compound 3',4',7-trihydroxyflavone
(12/12) with a MIC values ranging from 32 to 1024 MUg/mL, and 4 to 128 MUg/mL
respectively. The lowest MIC value (4 MUg/mL) was recorded with 3',4',7
trihydroxyflavone against Providencia stuartii ATCC299645 as well as the best MBC
value (16 MUg/mL) against the same strain. In the presence of Phenylalanine
Arginine-beta-Naphthylamide (PAbetaN), an efflux pumps inhibitor, the activity of
the extract increased on 73.33% (11/15) meanwhile that of 3',4',7
trihydroxyflavone increased on 100% tested bacteria. The compound 3',4',7
trihydroxyflavone potentiated the activity of antibiotics in the majority of the
tested bacterial strains. CONCLUSION: The results of the present work provide
additional information on the use of nutmeg and it major antibacterial component,
3',4',7-trihydroxyflavone, as a potential drug in the treatment of bacterial
infections including multidrug resistant phenotypes.
PMID- 29334932
TI - Anemia in people on second line antiretroviral treatment in Lilongwe, Malawi: a
cross-sectional study.
AB - BACKGROUND: Anemia is common among people living with HIV infection and is
frequently associated with poor quality of life and poor prognosis. It has been
well described in antiretroviral naive individuals and those on non-nucleoside
reverse transcriptase inhibitor-based first line antiretroviral therapy (ART)
regimens. However there is limited information on anemia for ART experienced
individuals on protease inhibitor-based second line ART regimens in resource
limited settings. Our objective was to describe the prevalence and risk factors
of anemia in this ART experienced population in Malawi. METHODS: We conducted a
cross-sectional study using routine facility data at two HIV clinics in Lilongwe,
Malawi. The analysis included individuals receiving protease inhibitor-based
second line ART. Clinical and laboratory data were collected at routine clinic
visits. We used descriptive statistics, two-sample t-tests and multivariate
logistic regression for data analysis. RESULTS: Three hundred seventy-seven
records were included in this analysis (37% male, median age 41 years, median CD4
count 415 cells/MUL). The prevalence of anemia was 125/377 (33.2%) - mild,
moderate and severe anemia was 17.5%, 13.8%, and 1.9% respectively. Female
participants had a higher prevalence than male participants (43.6% vs. 15.7%, p <
0.001). In multivariate logistic regression, female sex (adjusted odds ratio
(aOR) 5.3; 95% CI 2.9-9.5) and a CD4 count <200 cell/ul (aOR 3.1; 95%CI 1.6-6.0)
were associated with increased risk of having anemia while a BMI >=30 kg/m2 (aOR
0.8; 95% CI 0.6-1.0) and being on ART for more than 10 years (aOR 0.4; 95% CI 0.2
0.9) were associated with reduced risk of anemia. Being on a zidovudine-
containing ART regimen was not associated with anemia. CONCLUSION: Anemia is
common in people on second line ART in Lilongwe, Malawi. Screening for anemia in
this population would be a useful strategy; especially for female patients, those
who are underweight and have a low CD4 cell counts.
PMID- 29334933
TI - Temporary exclusion of ill children from childcare centres in Switzerland:
practice, problems and potential solutions.
AB - BACKGROUND: In childcare centres, temporary exclusion of ill children, if their
illness poses a risk of spread of harmful diseases to others, is a central
approach to fight disease transmission. However, not all ill children need to be
excluded. Previous studies suggested that childcare centre staff have
difficulties in deciding whether or not to exclude an ill child, even when
official ill-child guidelines are used. We aimed to describe, quantify and
analyse these ambiguities and discuss potential solutions. METHODS: For this
cross-sectional study, we sent postal surveys to 488 childcare centre directors
in the Swiss Canton of Zurich, where no official ill-child guideline is in place.
We asked for exclusion criteria for ill children and ambiguities faced when
dealing with ill children. We checked whether existing guidelines provided
solutions to the ambiguities identified. RESULTS: 249/488 (51%) directors
responded to the survey. The most common exclusion criteria were fever (87.4%)
and contagiousness (52.2%). Ambiguities were mostly caused by conjunctivitis
(23.7%) and use of antipyretic drugs (22.9%). Roughly one third of the
ambiguities identified could have been resolved with existing guidelines, another
third if existing guidelines contained additional information. For the last
third, clear written directives are difficult to formulate. CONCLUSIONS: Written
recommendations may help to clarify when an ill child should temporarily be
excluded. However, such a guideline should cover the topics antipyretic drugs and
teething and have room for modification to local circumstances. Collaboration
with a paediatrician may be of additional benefit.
PMID- 29334934
TI - Factors influencing the length of hospital stay of patients with anorexia nervosa
- results of a prospective multi-center study.
AB - BACKGROUND: The length of stay (LOS) strongly influences anorexia nervosa (AN)
inpatient weight outcomes. Hence, understanding the predictors of LOS is highly
relevant. However, the existing evidence is inconsistent and to draw conclusions,
additional evidence is required. METHODS: We conducted a prospective, multi
center study including adult female inpatients with AN. Using stepwise linear
regression, the following demographic and clinical variables were examined as
potential predictors for LOS: admission BMI, AN-subtype, age, age of onset,
living situation, partnership status, education, previous hospitalization, self
rated depression, anxiety and somatic symptoms (PHQ-9, PHQ-15, GAD-7), self-rated
therapy motivation (FEVER) and eating disorder psychopathology (EDI-2 subscale
scores). RESULTS: The average LOS of the sample (n = 176) was 11.8 weeks (SD =
5.2). Longer LOS was associated with lower admission BMI (beta = -1.66; p <
.001), purging AN-subtype (beta = 1.91; p = .013) and higher EDI-2 asceticism
(beta = 0.12; p = .030). Furthermore, differences between treatment sites were
evident. CONCLUSIONS: BMI at admission and AN-subtype are routinely assessed
variables, which are robust and clinically meaningful predictors of LOS. Health
care policies might consider these variables. In light of the differences between
treatment sites future research on geographical variations in mental health care
seems recommended.
PMID- 29334935
TI - Adoption and diffusion of zoning bylaws banning fast food drive-through services
across Canadian municipalities.
AB - BACKGROUND: Healthy public policy is an important tool for creating environments
that support human health and wellbeing. At the local level, municipal policies,
such as zoning bylaws, provide an opportunity for governments to regulate
building location and the type of services offered. Across North America, there
has been a recent proliferation of municipal bylaws banning fast food drive
through services. Research on the utilization of this policy strategy, including
bylaw adopters and adopter characteristics, is limited within the Canadian
context. The aim of this study was to identify and characterize Canadian
municipalities based on level of policy innovation and nature of their adopted
bylaw banning fast food drive-through services. METHODS: A multiple case history
methodology was utilized to identify and analyse eligible municipal bylaws, and
included development of a chronological timeline and map of adopter
municipalities within Canada. Grey literature and policy databases were searched
for potential adopters of municipal fast food drive-through service bylaws.
Adopters were confirmed through evidence of current municipal bylaws. Geographic
diffusion and diffusion of innovations theories provided a contextual framework
for analysis of bylaw documents. Analysis included assignment of adopter-types,
extent and purpose of bans, and policy learning activities of each adopter
municipality. RESULTS: From 2002 to 2016, 27 municipalities were identified as
adopters: six innovators and twenty-one early adopters. Mapping revealed parallel
geographic diffusion patterns in western and eastern Canada. Twenty-two
municipalities adopted a partial ban and five adopted a full ban. Rationales for
the drive-through bans included health promotion, environmental concerns from
idling, community character and aesthetics, traffic concerns, and walkability.
Policy learning, including research and consultation with other municipalities,
was performed by nine early adopters. CONCLUSION: This study detailed the
adoption of fast food drive-through bylaws across Canada. Understanding the
adopter-type characteristics of municipalities and the nature of their bylaws can
assist other jurisdictions in similar policy efforts. While the implications for
research and practice are evolving and dynamic, fast food drive-through service
bans may play a role in promoting healthier food environments. Further research
is required to determine the viability of this strategy for health promotion and
chronic disease prevention.
PMID- 29334936
TI - Gender-based violence screening methods preferred by women visiting a public
hospital in Pune, India.
AB - BACKGROUND: Gender-based violence (GBV) is a major global public health concern
and is a risk factor for adverse health outcomes. Early identification of GBV is
crucial for improved health outcomes. Interactions with health care providers may
provide a unique opportunity for routine GBV screening, if a safe, confidential
environment can be established. METHODS: Between November 2014 and February 2015,
a cross-sectional, observational study was conducted where women were interviewed
about their opinions concerning GBV screening in a tertiary health care setting
in Pune, India. Trained counsellors interviewed 300 women at different out
patient and in-patient departments using a semi-structured questionnaire.
RESULTS: Twenty-three percent of these women reported experiencing GBV in their
life. However, 90% of women said they had never been asked about GBV in a health
care setting. Seventy-two percent expressed willingness to be asked about GBV by
their health care providers, with the preferred provider being nurses or
counsellors. More than half (53%) women reported face-to-face interview as the
most preferred method for screening. There were no major differences in these
preferences by GBV history status. CONCLUSIONS: Our study provides evidence for
preferred GBV screening methods and optimal provider engagement as perceived by
women attending a public hospital.
PMID- 29334937
TI - Perspectives on setting limits for RF contact currents: a commentary.
AB - BACKGROUND: Limits for exposure to radiofrequency (RF) contact currents are
specified in the two dominant RF safety standards and guidelines developed by the
Institute of Electrical and Electronics Engineers (IEEE) and the International
Commission on Non-Ionizing Radiation Protection (ICNIRP). These limits are
intended to prevent RF burns when contacting RF energized objects caused by high
local tissue current densities. We explain what contact currents are and review
some history of the relevant limits with an emphasis on so-called "touch"
contacts, i.e., contact between a person and a contact current source during
touch via a very small contact area. RESULTS: Contact current limits were
originally set on the basis of controlling the specific absorption rate resulting
from the current flowing through regions of small conductive cross section within
the body, such as the wrist or ankle. More recently, contact currents have been
based on thresholds of perceived heating. In the latest standard from the IEEE
developed for NATO, contact currents have been based on two research studies in
which thresholds for perception of thermal warmth or thermal pain have been
measured. Importantly, these studies maximized conductive contact between the
subject and the contact current source. This factor was found to dominate the
response to heating wherein high resistance contact, such as from dry skin, can
result in local heating many times that from a highly conductive contact. Other
factors such as electrode size and shape, frequency of the current and the
physical force associated with contact are found to introduce uncertainty in
threshold values when comparing data across multiple studies. CONCLUSIONS:
Relying on studies in which the contact current is minimized for a given
threshold does not result in conservative protection limits. Future efforts to
develop limits on contact currents should include consideration of (1) the basis
for the limits (perception, pain, tissue damage); (2) understanding of the
practical conditions of real world exposure for contact currents such as contact
resistance, size and shape of the contact electrode and applied force at the
point of contact; (3) consistency of how contact currents are applied in research
studies across different researchers; (4) effects of frequency.
PMID- 29334938
TI - Therapeutic plasma exchange in a tertiary care center: 185 patients undergoing
912 treatments - a one-year retrospective analysis.
AB - BACKGROUND: Therapeutic plasma exchange (TPE) is increasingly used throughout the
world. Although the procedure itself is fairly standardized, it is yet unknown
how the underlying disease entities influence the key coordinates of the
treatment. METHODS: Retrospective chart review. The treatment indications were
clustered into four categories. Data are presented as median and interquartile
(25-75%) range [IQR]. RESULTS: Within 1 year, 912 TPE treatments were performed
in 185 patients (90 female, 48.6%). The distribution of the treatment numbers to
the pre-specified disease categories were as follows: transplantation (35.7%),
neurology (31.9%), vasculitis and immunological disease (17.3%), and others
including thrombotic microangiopathy (8.1%), critical care related diseases
(5.4%), hematology [multiple myeloma] (1.1%), and endocrine disorders (0.5%). The
calculated plasma volume was significantly higher in patients with vasculitis and
immunological diseases (3984 [3433-4439] ml) as compared to patients treated for
transplant related indications (3194 [2545-3658] ml; p = 0.0003) and neurological
diseases (3058 [2533-3359] ml; p < 0.0001). This was mainly due to the
differences in the hematocrit which was 30.5 [27.0-33.6] % in the
vasculitis/immunological disease patients and 40.2 [37.5-42.9] % in the
neurological patients; p < 0.0001. Interestingly, treatment time using a membrane
based technology was significantly longer than TPE using a centrifugal device
135.0 [125.0-140.0] min vs. 120.0 [112.5-135.0] min. Furthermore, the relative
exchanged plasma volume was significantly lower in the treatment of vasculitis
and immunological diseases as compared to treatments of transplant related
indications and neurological diseases. CONCLUSION: Patients with low hematocrit
and high body weight do not receive the minimum recommended dose of exchange
volume. Centrifugal TPE allowed faster plasma exchange than membrane TPE.
PMID- 29334939
TI - Choosing a career in oncology: results of a nationwide cross-sectional study.
AB - BACKGROUND: Little information is currently available concerning young medical
students desire to pursue a career in oncology, or their career expectations.
METHODS: This project is a cross-sectional epidemiological study. A voluntary and
anonymous questionnaire was distributed to all young oncologists studying in
France between the 2nd of October 2013 and the 23rd of February 2014. RESULTS:
The overall response rate was 75.6%. A total of 505 young oncologists completed
the questionnaire. The main determining factors in the decision to practice
oncology were the cross-sectional nature of the field (70.8%), the depth and
variety of human relations (56.3%) and the multi-disciplinary field of work
(50.2%). Most residents would like to complete a rotation outside of their
assigned region (59.2%) or abroad (70.2%) in order to acquire additional
expertise (67.7%). In addition, most interns would like to undertake a fellowship
involving care, teaching and research in order to hone their skills (85.7%) and
forge a career in public hospitals (46.4%). Career prospects mainly involve
salaried positions in public hospitals. Many young oncologists are concerned
about their professional future, due to the shortage of openings (40.8%), the
workload (52.8%) and the lack of work-life balance (33.4%). CONCLUSIONS: This
investigation provides a comprehensive profile of the reasons young oncologists
chose to pursue a career in oncology, and their career prospects.
PMID- 29334940
TI - Correction to: The transcriptome landscape of early maize meiosis.
AB - CORRECTION: Following publication of the original article [1], the authors
reported that the number of genes overlaying the bar graph in Fig. 3A were
incorrectly counted and inserted (i.e. including a title tile, and in inverse
order). The corrected numbers are below and match with the listed genes supplied
in Additional File: Table S2.
PMID- 29334941
TI - The association of the N-terminal pro-brain-type natriuretic peptide response to
exercise with disease severity in therapy-naive pulmonary arterial hypertension:
a cohort study.
AB - BACKGROUND: While the N-terminal pro-brain-type natriuretic peptide (NT-proBNP)
at rest is known to be associated with prognosis in pulmonary arterial
hypertension (PAH), it is unclear if the NT-proBNP response to exercise (DeltaNT
proBNP) can contribute to a better assessment of disease severity. METHODS: We
investigated the association of NT-proBNP values at rest and during peak exercise
with hemodynamics and cardiopulmonary exercise testing parameters in 63 therapy
naive PAH patients. RESULTS: The median NT-proBNP increases from 1414 at rest to
1500 pg/ml at peak exercise. The DeltaNT-proBNP is baseline-dependent in PAH.
Both, NT-proBNP at rest and NT-proBNP at peak exercise, are significantly
correlated with hemodynamics and functional capacity. However, neither NT-proBNP
at peak exercise nor DeltaNT-proBNP correlated better with surrogate markers of
disease severity than NT-proBNP at rest. CONCLUSION: The DeltaNT-proBNP does not
contribute to a better assessment of disease severity in PAH.
PMID- 29334942
TI - Poor response to artesunate treatment in two patients with severe malaria on the
Thai-Myanmar border.
AB - BACKGROUND: Malaria has declined dramatically along the Thai-Myanmar border in
recent years due to malaria control and elimination programmes. However, at the
same time, artemisinin resistance has spread, raising concerns about the efficacy
of parenteral artesunate for the treatment of severe malaria. CASE PRESENTATION:
In November 2015 and April 2017, two patients were treated for severe malaria
with parenteral artesunate. Quinine was added within 24 h due to an initial poor
response to treatment. The first patient died within 24 h of starting treatment
and the second did not clear his peripheral parasitaemia until 11 days later.
Genotyping revealed artemisinin resistance Kelch-13 markers. CONCLUSIONS:
Reliable efficacy of artesunate for the treatment of severe malaria may no longer
be assured in areas where artemisinin resistance has emerged. Empirical addition
of parenteral quinine to artesunate for treatment is recommended as a
precautionary measure.
PMID- 29334943
TI - Training programmes to improve evidence uptake and utilisation by
physiotherapists: a systematic scoping review.
AB - BACKGROUND: Research training programmes are a knowledge translation (KT)
intervention which aim to improve research evidence uptake by clinicians. Whilst
KT training programmes have been reported to significantly improve evidence
uptake by physiotherapists, it is unclear which aspects of training optimally
assist KT into physiotherapy practice. The purpose of the review was to establish
the body of evidence regarding KT training programmes to improve
physiotherapists' use of evidence-based practice (EBP) and clinical practice
guidelines (CPG). METHODS: A systematic scoping review was undertaken in line
with the adapted Arksey and O'Malley framework. Nine electronic databases
(CINAHL, BIOMED CENTRAL, Cochrane, Web of Science, PROQUEST, PUBMED, OTseeker,
Scopus, ERIC) were searched. Targeted keywords identified primary research
articles of any hierarchy, that described the nature and impact of KT training
programmes for physiotherapists. Where systematic reviews were identified, the
component primary studies were considered individually for relevance. Critical
appraisal was not undertaken due to the nature of a scoping review, and data was
reported descriptively. RESULTS: Ten systematic reviews were identified (yielding
four relevant primary studies). Five additional primary studies were identified
(two randomised controlled trials, two non-randomised controlled trials and one
pre-post study) which were not included in the original systematic reviews. This
provided nine eligible primary research studies for review. The KT strategies
were all multi-faceted. Interactive sessions, didactic sessions, printed material
and discussion and feedback were consistently associated with effective outcomes.
When KT strategies addressed local barriers to EBP utilisation, there were better
success rates for EBP and CPG uptake, irrespective of the outcome measures used.
There were no consistent ways of measuring outcome. CONCLUSION: Multi-faceted KT
strategies designed to address local barriers to knowledge translation were most
effective in improving EBP/ CPG uptake among physiotherapists.
PMID- 29334944
TI - Changes in malaria epidemiology in Germany, 2001-2016: a time series analysis.
AB - BACKGROUND: German surveillance data showed a sharp rise of malaria cases in 2014
and 2015 due to the increased arrival of refugees from malaria endemic countries.
A time series analysis of data from 2001 to 2016 was performed in order to
describe the epidemiology of imported malaria in Germany in general and of the
recent increase in particular. RESULTS: In total, 11,678 malaria cases were
notified between 2001 and 2016 (range 526-1063 cases/year). Newly arriving
refugees averaged 10 cases/year (1.5%) in 2001-13 and 292.5 cases/year (28.3%) in
2014-15. Plasmodium (P.) falciparum was the most frequently reported species
(range 57.2-85.8%), followed by P. vivax (range during 2001-2013: 7.6-18.1%;
during 2014-2015, mean 31.3%). In 2014-15, 22.3% of all P. vivax cases were
refugees from Eritrea and 3.3% from other countries of the Horn of Africa; in
2015 and 2016, 19.5% were refugees from Afghanistan and Pakistan. Five P.
knowlesi malaria infections were reportedly acquired in Thailand between 2012 and
2016. Total numbers of malaria notifications among native Germans and residents
with migration background showed an increasing trend since 2007. Chemoprophylaxis
use was reported for 24.3% (1695/6984) of cases and showed a declining trend.
Native German cases took significantly more frequently chemoprophylaxis than
cases with migration background (32.6% vs. 17.9%; p < 0.001).
DISCUSSION/CONCLUSIONS: The steep rise in vivax malaria notifications in 2014 and
2015 was mainly due to newly arriving refugees from Eritrea but also from other
countries of the Horn of Africa and South Asia. Clinicians should include malaria
in their differential diagnosis in case of a febrile illness in the respective
population and consider vivax malaria even if arrival to Germany dates back
several months. Over the past 10 years, malaria notifications among native
Germans and residents with migration background showed an increasing trend. Use
of chemoprophylaxis was insufficient in both groups and deteriorating. New
strategies need to be found to increase compliance to chemoprophylaxis
recommendations. The surveillance provides valuable data for epidemiological
assessment of imported malaria in Germany.
PMID- 29334946
TI - Surmounting difficulties to provide home based neonatal care - reflections of
community health workers.
AB - BACKGROUND: In India, community health workers' (CHW) effectiveness in providing
home-based neonatal care (HBNC) has been well documented. The nature of
challenges faced and strategies adopted while providing HBNC services need to be
studied in-depth. METHODS: A qualitative study to understand the challenges faced
and strategies used by Sakhis (women CHW) while providing services as part of a
HBNC program implemented by a non-profit organization. Data consisted of 20 in
depth interviews and three focus group discussions (FGD) with Sakhis. RESULTS:
Sakhis negotiated with the community to start working as a CHW. They faced
challenges while changing behaviors at individual level and also while bringing
about a change in harmful normative practices that increased chances of maternal
and neonatal mortality. Managing crises at the time of deliveries and
facilitating a safe delivery was the most critical challenge faced by many
Sakhis. The key strategies used by Sakhis included: proactively and persistently
providing services even when they faced resistance from the woman or her family;
evolving contextually suitable counseling techniques and tactics to bring about
behavioral change; balancing compliance to traditional practices and promoting
HBNC; defying traditional practices and assisting the woman in times of an
emergency to save lives. Having on-call support from supervisors and cultivating
a good working relationship with health providers facilitated effective service
provision by Sakhis. CONCLUSION: CHWs having a strong sense of commitment can
develop strategies to address challenges and provide HBNC services effectively if
they also have strong supervisory support.
PMID- 29334945
TI - Blood pressure change does not associate with Center of Pressure movement after
postural transition in geriatric outpatients.
AB - BACKGROUND: Orthostatic hypotension (OH), a blood pressure drop after postural
change, is associated with impaired standing balance and falls in older adults.
This study aimed to assess the association between blood pressure (BP) and a
measure of quality of standing balance, i.e. Center of Pressure (CoP) movement,
after postural change from supine to standing position in geriatric outpatients,
and to compare CoP movement between patients with and without OH. METHODS: In a
random subgroup of 75 consecutive patients who were referred to a geriatric
outpatient clinic, intermittent BP measurements were obtained simultaneously with
CoP measurements in mediolateral and anterior-posterior direction directly after
postural change during 3 min of quiet stance with eyes open on a force plate.
Additional measurements of continuous BP were available in n = 38 patients.
Associations between BP change during postural change and CoP movement were
analyzed using Spearman correlation. Mann-Whitney-U tests were used to compare
CoP movement between patients with OH and without OH, in which OH was defined as
a BP drop exceeding 20 mmHg of systolic BP (SBP) and/or 10 mmHg of diastolic BP
(DBP) within 3 min after postural change. RESULTS: OH measured intermittently was
found in 8 out of 75 (11%) and OH measured continuously in 22 out of 38 patients
(57.9%). BP change did not associate with CoP movement. CoP movement did not
differ significantly between patients with and without OH. CONCLUSIONS: Results
do not underpin the added value of CoP movement measurements in diagnosing OH in
a clinical setting. Neither could we identify the role of CoP measurements in the
understanding of the relation between OH and impaired standing balance.
PMID- 29334948
TI - Molecular identification and investigations of contagious ecthyma (Orf virus) in
small ruminants, North west Ethiopia.
AB - BACKGROUND: Orf virus, the prototype of parapoxvirus, is the main causative agent
of contagious ecthyma. Little is known about the status of the disease in
Ethiopia and this study was aimed at determining its status using PCR as a
confirmatory tool. METHODS: a total of 400 randomly selected sheep and goat was
screened for the identification of the virus using amplification of B2L gene and
transfection of mammalian cells (VERO cells). RESULTS: Out of 400 animals
screened for infection of the virus, 48 animals were found positive to PCR and
revealed an overall incidence of 12%. Different epidemiological parameters were
considered to look at the association with incidence of the disease and of which,
only species of the animal(sheep), non-vaccinated and non-treated animals,
nursing animals, poor body condition animals, extensively managed animals,
animals having mouth lesion, and study areas having outbreak history showed
higher prevalence. A univariate logistic regression analysis showed statistically
significant difference in all variables (P < 0.05). Whereas, age and sex of
animals showed no significant difference (P < 0.05). CONCLUSION: The result of
the present finding showed high incidence of Orf virus in the region as confirmed
through PCR.
PMID- 29334947
TI - Effects of hypoxia and hyperoxia on the differential expression of VEGF-A
isoforms and receptors in Idiopathic Pulmonary Fibrosis (IPF).
AB - Dysregulation of VEGF-A bioavailability has been implicated in the development of
lung injury/fibrosis, exemplified by Idiopathic Pulmonary Fibrosis (IPF). VEGF-A
is a target of the hypoxic response via its translational regulation by HIF
1alpha. The role of hypoxia and hyperoxia in the development and progression of
IPF has not been explored. In normal lung (NF) and IPF-derived fibroblasts (FF)
VEGF-Axxxa protein expression was upregulated by hypoxia, mediated through
activation of VEGF-Axxxa gene transcription. VEGF-A receptors and co-receptors
were differentially expressed by hypoxia and hyperoxia. Our data supports a
potential role for hypoxia, hyperoxia and VEGF-Axxxa isoforms as drivers of
fibrogenesis.
PMID- 29334949
TI - Flaxseed-enriched diets change milk concentration of the antimicrobial
danofloxacin in sheep.
AB - BACKGROUND: Flaxseed is the most common and rich dietary source of lignans and is
an acceptable supply of energy for livestock. Flaxseed lignans are precursors of
enterolignans, mainly enterolactone and enterodiol, produced by the rumen and
intestinal microbiota of mammals and have many important biological properties as
phytoestrogens. Potential food-drug interactions involving flaxseed may be
relevant for veterinary therapy, and for the quality and safety of milk and dairy
products. Our aim was to investigate a potential food-drug interaction involving
flaxseed, to explore whether the inclusion of flaxseed in sheep diet affects
concentration of the antimicrobial danofloxacin in milk. RESULTS: Increased
concentrations of enterodiol and enterolactone were observed in sheep plasma and
milk after 2 weeks of flaxseed supplementation (P < 0.05). However, enterolactone
and enterodiol conjugates were not detected in milk. Milk danofloxacin
pharmacokinetics showed that area under the curve (AUC)0-24, maximum
concentration (Cmax) and AUC0-24 milk-to-plasma ratios were reduced by 25-30% in
sheep fed flaxseed-enriched diets (P < 0.05). Our results demonstrate, therefore,
that flaxseed-enriched diets reduce the amount of danofloxacin in sheep milk and
enrich the milk content of lignan-derivatives. CONCLUSION: These findings
highlight an effect of flaxseed-enriched diets on the concentration of
antimicrobials in ruminant's milk, revealing the potential of these modified
diets for the control of residues of antimicrobial drugs in milk.
PMID- 29334950
TI - Will human influences on evolutionary dynamics in the wild pervade the
Anthropocene?
AB - The five most pervasive anthropogenic threats to biodiversity are over
exploitation, habitat changes, climate change, invasive species, and pollution.
Since all of these threats can affect intraspecific biodiversity-including
genetic variation within populations-humans have the potential to induce
contemporary microevolution in wild populations. We highlight recent empirical
studies that have explored the effects of these anthropogenic threats to
intraspecific biodiversity in the wild. We conclude that it is critical that we
move towards a predictive framework that integrates a better understanding of
contemporary microevolution to multiple threats to forecast the fate of natural
populations in a changing world.
PMID- 29334951
TI - The surprising implications of familial association in disease risk.
AB - BACKGROUND: A wide range of diseases show some degree of clustering in families;
family history is therefore an important aspect for clinicians when making risk
predictions. Familial aggregation is often quantified in terms of a familial
relative risk (FRR), and although at first glance this measure may seem simple
and intuitive as an average risk prediction, its implications are not
straightforward. METHODS: We use two statistical models for the distribution of
disease risk in a population: a dichotomous risk model that gives an intuitive
understanding of the implication of a given FRR, and a continuous risk model that
facilitates a more detailed computation of the inequalities in disease risk.
Published estimates of FRRs are used to produce Lorenz curves and Gini indices
that quantifies the inequalities in risk for a range of diseases. RESULTS: We
demonstrate that even a moderate familial association in disease risk implies a
very large difference in risk between individuals in the population. We give
examples of diseases for which this is likely to be true, and we further
demonstrate the relationship between the point estimates of FRRs and the
distribution of risk in the population. CONCLUSIONS: The variation in risk for
several severe diseases may be larger than the variation in income in many
countries. The implications of familial risk estimates should be recognized by
epidemiologists and clinicians.
PMID- 29334952
TI - Predictors of overweight/obesity in a Brazilian cohort after 13 years of follow
up.
AB - BACKGROUND: Obesity is a chronic complex disease with an increasing prevalence
around the world. Prospective studies in adult cohorts are needed to provide
information about predictors of new-onset overweight/obesity on population-based
levels. The aim of this study was to identify factors associated with the risk of
an adult individual become overweight/obese after 13 years of follow-up. METHODS:
Second phase of an observational population-based prospective cohort study in a
small town in the Midwest region of Brazil. A representative sample of the adult
population (>=18 years) was assessed in 2002 (phase 1). Anthropometric,
sociodemographic, dietary intake and lifestyle data were collected. After 13
years of follow-up (2015), the same variables were re-evaluated (phase 2). New
onset overweight/obesity was the outcome variable. RESULTS: A total of 685
subjects were included with a mean age in phase 1 of 42.7 +/- 13.8 years and 56.1
+/- 13.8 years in phase 2, the mean follow-up time was 13.2 years and female sex
counted for 66.3% of the sample. Total weight gain was 5.9 +/- 10.2 Kg, body mass
index increased 2.6 +/- 3.8 Kg/m2 and waist circumference (WC) values increased
8.0 +/- 10.5 cm. The prevalence of overweight/obesity went from 49.1% in phase 1
to 69.8% in phase 2 (p < 0.001). The factors associated with a decreased risk of
new-onset overweight/obesity were ages between 50 and 64 (RR 0.40; CI 0.24-0.67 -
p = 0.001) and >=65 years (RR 0.15; CI 0.06-0.35 - p < 0.001), being part of the
second quartile of fat consumption (RR 0.59; CI 0.35-0.97 - p = 0.041), no
alcohol consumption (RR 0.59; CI 0.37-0.93 - p = 0.024) and smoking (RR 0.58; CI
0.39-0.86 - p = 0,007) in phase 1. CONCLUSIONS: We identified in thirteen years
of follow-up that older ages, a moderate fat consumption compared to low
consumption, no alcohol consumption and smoking habit were related to a decreased
risk of new-onset overweight/obesity. Obesity prevention actions must focus on
subjects at younger ages and include policies to reduce alcohol consumption.
PMID- 29334953
TI - Care relationships at stake? Home healthcare professionals' experiences with
digital medicine dispensers - a qualitative study.
AB - BACKGROUND: Although digital technologies can mitigate the burdens of home
healthcare services caused by an ageing population that lives at home longer with
complex health problems, research on the impacts and consequences of digitalised
remote communication between patients and caregivers is lacking. The present
study explores how home healthcare professionals had experienced the introduction
of digital medicine dispensers and their influence on patient-caregiver
relationships. METHODS: The multi-case study comprised semi-structured interviews
with 21 healthcare professionals whose home healthcare service involved using the
digital medicine dispensers. The constant comparative method was used for data
analyses. RESULTS: Altogether, interviewed healthcare professionals reported
three main technology-related impacts upon their patient-caregiver relationships.
First, national and local pressure to increase efficiency had troubled their
relationships with patients who suspected that municipalities have sought to
lower costs by reducing and digitalising services. Participants reported having
to consider such worries when introducing technologies into their services.
Second, participants reported a shift towards empowering patients. Digital
technology can empower patients who value their independence, whereas safety is
more important for other patients. Healthcare professionals needed to ensure that
replacing care tasks with technology implies safe and improved care. Third, the
safety and quality of digital healthcare services continues to depend upon
surveillance and control mechanisms that compensate for less face-to-face
monitoring. Participants did not consider the possibility that surveillance
exposes information about patients' everyday lives to be problematic, but to
constitute opportunities for adjusting services to meet patients' needs.
CONCLUSIONS: Technologies such as digital medicine dispensers can improve the
efficiency of healthcare services and enhance patients' independence when
introduced in a way that empowers patients as well as safeguards trust and
service quality. Conversely, the patient-caregiver relationship can suffer if the
technology does not meet patients' needs and fails to offer safe and trustworthy
services. Upon introducing technology, home healthcare professionals therefore
need to carefully consider the benefits and possible disadvantages of the
technology. Ethical implications for both individuals and societies need to be
further discussed.
PMID- 29334954
TI - Association between non-cholesterol sterol concentrations and Achilles tendon
thickness in patients with genetic familial hypercholesterolemia.
AB - BACKGROUND: Familial hypercholesterolemia (FH) is a genetic disorder that result
in abnormally high low-density lipoprotein cholesterol levels, markedly increased
risk of coronary heart disease (CHD) and tendon xanthomas (TX). However, the
clinical expression is highly variable. TX are present in other metabolic
diseases that associate increased sterol concentration. If non-cholesterol
sterols are involved in the development of TX in FH has not been analyzed.
METHODS: Clinical and biochemical characteristics, non-cholesterol sterols
concentrations and Aquilles tendon thickness were determined in subjects with
genetic FH with (n = 63) and without (n = 40) TX. Student-t test o Mann-Whitney
test were used accordingly. Categorical variables were compared using a Chi
square test. ANOVA and Kruskal-Wallis tests were performed to multiple
independent variables comparison. Post hoc adjusted comparisons were performed
with Bonferroni correction when applicable. Correlations of parameters in
selected groups were calculated applying the non-parametric Spearman correlation
procedure. To identify variables associated with Achilles tendon thickness
changes, multiple linear regression were applied. RESULTS: Patients with TX
presented higher concentrations of non-cholesterol sterols in plasma than
patients without xanthomas (P = 0.006 and 0.034, respectively). Furthermore,
there was a significant association between 5alpha-cholestanol, beta-sitosterol,
desmosterol, 24S-hydroxycholesterol and 27-hydroxycholesterol concentrations and
Achilles tendon thickness (p = 0.002, 0.012, 0.020, 0.045 and 0.040,
respectively). CONCLUSIONS: Our results indicate that non-cholesterol sterol
concentrations are associated with the presence of TX. Since cholesterol and non
cholesterol sterols are present in the same lipoproteins, further studies would
be needed to elucidate their potential role in the development of TX.
PMID- 29334955
TI - The inverted cup device for blood transfer on malaria RDTs: ease of use,
acceptability and safety in routine use by health workers in Nigeria.
AB - BACKGROUND: Malaria rapid diagnostic tests (RDTs) are becoming widely adopted for
case management at community level. However, reports and anecdotal observations
indicate that the blood transfer step poses a significant challenge to many
users. This study sought to evaluate the inverted cup device in the hands of
health workers in everyday clinical practice, in comparison with the plastic
pipette, and to determine the volume accuracy of the device made of a lower-cost
plastic. METHODS: The volume accuracy of inverted cup devices made of two
plastics, PMMA and SBC, was compared by transferring blood 150 times onto filter
paper and comparing the blood spot areas with those produced by 20 reference
transfers with a calibrated micropipette. The ease of use, safety and
acceptability of the inverted cup device and the pipette were evaluated by 50
health workers in Nigeria. Observations were recorded on pre-designed
questionnaires, by the health workers themselves and by trained observers. Focus
group discussions were also conducted. RESULTS: The volume accuracy assessment
showed that the device made from the low-cost material (SBC) delivered a more
accurate volume (mean 5.4 MUL, SD 0.48 MUL, range 4.5-7.0 MUL) than the PMMA
device (mean 5.9 MUL, SD 0.48 MUL, range 4.9-7.2 MUL). The observational
evaluation demonstrated that the inverted cup device performed better than the
pipette in all aspects, e.g. higher proportions of health workers achieved
successful blood collection (96%, vs. 66%), transfer of the required blood volume
(90%, vs. 58%), and blood deposit without any loss (95%, vs. 50%). Majority of
health workers also considered it' very easy' to use (81%),'very appropriate' for
everyday use (78%), and 50% of them reported that it was their preferred BTD.
CONCLUSIONS: The good volume accuracy and high acceptability of the inverted cup
device shown in this study, along with observed ease of use and safety in hands
of health workers, further strengthens prior findings which demonstrated its
higher accuracy as compared with other BTDs in a laboratory setting. Altogether,
these studies suggest that the inverted cup device should replace other types of
devices for use in day-to-day malaria diagnosis with RDTs.
PMID- 29334956
TI - Identification and characterization of areas of high and low risk for
asymptomatic malaria infections at sub-village level in Ratanakiri, Cambodia.
AB - BACKGROUND: Malaria elimination needs a concentration of activities towards
identification of residual transmission foci and intensification of efforts to
eliminate the last few infections, located in so-called 'malaria hotspots'.
Previous work on characterizing malaria transmission hotspots has mainly focused
on falciparum malaria and especially on symptomatic cases, while the malaria
reservoir is expected to be mainly concentrated in the asymptomatic human
population when transmission is low. For Plasmodium vivax, there has been less
effort in identifying transmission hotspots. The main aim of this study was to
uncover micro-epidemiological mechanisms of clustering of malaria infections at a
sub-village level, based on geographical or behavioural features. METHODS: A
cross-sectional survey was performed in three villages within the highest malaria
endemic province of Cambodia. The survey took place in the dry season, when the
malaria reservoir is expected to be low and residing in the asymptomatic part of
the population. Village and field locations of households were georeferenced,
blood samples were taken from as many residents as possible and a short
questionnaire probing for individual risk factors was taken. Asymptomatic malaria
carriers were detected by PCR, and geographical clustering analysis (SaTScan) as
well as risk factor analysis were performed. RESULTS: A total of 1540 out of 1792
(86%) individuals were sampled. Plasmodial DNA was detected in 129 individuals
(8.4%). P. vivax was most prevalent (5.5%) followed by Plasmodium malariae (2.1%)
and Plasmodium falciparum (1.6%). Mixed infection occurred in 12 individuals. In
two out of three villages geographical clustering of high and low malaria
infection risk was clearly present. Cluster location and risk factors associated
with the infection differed between the parasite species. Age was an important
risk factor for the combined Plasmodium infections, while watching television at
evenings was associated with increased odds of P. vivax infections [OR (CI): 1.86
(0.95-3.64)] and bed net use was associated with reduced odds of P. falciparum
infections [OR (CI): 0.25 (0.077-0.80)]. CONCLUSIONS: Clusters of malaria
carriers were malaria species specific and often located remotely, outside
village centres. As such, at micro-epidemiological level, malaria is not a single
disease. Further unravelling the micro-epidemiology of malaria can enable
programme managers to define the interventions likely to contribute to halt
transmission in a particular hotspot location.
PMID- 29334957
TI - Vertebral column decancellation in Pott's deformity: use of Surgimap Spine for
preoperative surgical planning, retrospective review of 18 patients.
AB - BACKGROUND: In the late stage of Spinal tuberculosis, the bony destruction and
vertebral collapse often leads to significant kyphosis, presenting clinically as
a painful gibbus deformity, with increased instability, vertebral body
translations and increased risk of neurologic involvement. Vertebral column
decancellation is thought to be suitable for most patients with severe rigid
kyphosis. Surgimap Spine, could offer a pragmatic graphical method for the
surgical planning of osteotomies. The aim of this study was to evaluate the
efficacy of Vertebral column decancellation planned preoperatively with the
computer software-assistance in the patients with Pott's kyphosis. METHODS:
Between May 2012 and May 2015, 18 patients with Pott's kyphosis underwent the
Vertebral column decancellation using Surgimap Spine for preoperative surgical
planning. Preoperative and postoperative Konstam's angle, sagittal vertical
angle, lumbar lordosis, thoracic kyphosis, pelvic tilt and pelvic incidence were
measured. Visual analog scale and American Spinal Injury Association were
documented. RESULTS: The Konstam's angles decreased from 88.1 degrees (range, 70
105 degrees ) preoperatively to 18.5 degrees (range, 7-31 degrees ) (P < 0.01).
All patients reached the physiological limits at the final follow-up. The mean
VAS score was reduced from preoperative 7.1 (range, 6-8) to 1.8 (range, 1-3, P <
0.01) and the ODI improved from 65.8% (range, 58-74%) to 20.2% (range, 12-38%, P
< 0.01). At final follow-up, there was radiographic evidence of solid fusion at
the osteotomy site and fixed segments in all patients. Neurological function
improved from ASIA scale D to E in 5 patients. The patients were followed up for
30.4 months on average. CONCLUSION: Vertebral column decancellation is an
effective treatment option for severe Pott's kyphosis. The surgical planning
software Surgimap Spine can be a reliable and helpful tool that provides a
simplified method to evaluate and analyze the spino-pelvic parameters and
simulate the osteotomy procedure. According to individual character, the
appropriate surgery strategy should be selected.
PMID- 29334958
TI - Clinical rationale and safety of restaging transurethral resection in indication
stratified patients with high-risk non-muscle-invasive bladder cancer.
AB - BACKGROUND: Indications for restaging transurethral resection of the bladder
tumor (reTURBT) in patients with non-muscle-invasive bladder cancer (NMIBC)
remain controversial. This study was aimed at evaluation of clinical value and
safety of reTURBT in different clinical indications. METHODS: This is a
retrospective analysis of consecutive 141 patients who underwent TURBT followed
by reTURBT in years 2011-2015 in a single department. Pathological results and
surgical complications were analyzed in the whole study cohort and stratified by
clinical stage (Ta, T1, Tx (no muscle in the specimen)) and grade (low-grade
(LG), high-grade (HG)) of bladder cancer diagnosed at primary TURBT. RESULTS:
Full data was available for 132 patients. Residual disease was found in 53
patients (40.2%) with highest rate for Ta-HG cases (57.1%) followed by T1-HG
(51.4%), Tx-HG (45.2%), T1-LG (32.1%), and Tx-LG (25.8%). In the multivariate
analysis, high grade (p = 0.02) was the only independent predictor of residual
disease. Upstaging to muscle-invasive bladder cancer was noticed in 9 patients
(6.8%). The rate of grade >= 2 Clavien-Dindo complications (1.5 vs. 5.3%) did not
differ significantly between TURBT and reTURBT cases. CONCLUSIONS: ReTURBT is a
safe procedure that remains crucial for therapeutic and staging purposes in
patients with T1, Tx, or high-grade bladder cancer found in the primary
resection.
PMID- 29334959
TI - A structural equation model of perceived and internalized stigma, depression, and
suicidal status among people living with HIV/AIDS.
AB - BACKGROUND: Previous studies have shown positive association between HIV-related
stigma and depression, suicidal ideation, and suicidal attempt among people
living with HIV/AIDS (PLWH). But few studies have examined the mechanisms among
HIV-related stigma, depression, and suicidal status (suicidal ideation and/or
suicidal attempt) in PLWH. The current study examined the relationships among
perceived and internalized stigma (PIS), depression, and suicidal status among
PLWH in Guangzhou, China using structural equation modeling. METHODS: Cross
sectional study by convenience sampling was conducted and 411 PLWH were recruited
from the Number Eight People's Hospital from March to June, 2013 in Guangzhou,
China. Participants were interviewed on their PIS, depressive symptoms, suicidal
status, and socio-demographic characteristics. PLWH who had had suicidal ideation
and suicidal attempts since HIV diagnosis were considered to be suicidal.
Structural equation model was performed to examine the direct and indirect
associations of PIS and suicidal status. Indicators to evaluate goodness of fit
of the structural equation model included Chi-square Statistic, Comparative Fit
Index (CFI), Root Mean Square Error of Approximation (RMSEA), Standardized Root
Mean Square Residual (SRMR), and Weighted Root Mean Square Residual (WRMR).
RESULTS: More than one-third (38.4%) of the PLWH had depressive symptoms and
32.4% reported suicidal ideation and/or attempt since HIV diagnosis. The global
model showed good model fit (Chi-square value = 34.42, CFI = 0.98, RMSEA = 0.03,
WRMR = 0.73). Structural equation model revealed that direct pathway of PIS on
suicidal status was significant (standardized pathway coefficient = 0.21), and
indirect pathway of PIS on suicidal status via depression was also significant
(standardized pathway coefficient = 0.24). There was a partial mediating effect
of depression in the association between PIS and suicidal status. CONCLUSIONS:
Our findings suggest that PIS is associated with increased depression and the
likelihood of suicidal status. Depression is in turn positively associated with
suicidal status and plays a mediating role between PIS and suicidal status.
Therefore, to reduce suicidal ideation and attempt in PLWH, targeted
interventions to reduce PIS and improve mental health status of PLWH are
warranted.
PMID- 29334960
TI - Arsenic exposure and risk of nonalcoholic fatty liver disease (NAFLD) among U.S.
adolescents and adults: an association modified by race/ethnicity, NHANES 2005
2014.
AB - BACKGROUND: While associated with obesity, the cause of the rapid rise in
prevalence of nonalcoholic fatty liver disease (NAFLD) in children, which is
highest among Hispanics, is not well understood. Animal experiments have
demonstrated that arsenic exposure contributes to liver injury. Our objective was
to examine the association between arsenic exposure and NAFLD in humans and to
determine if race/ethnicity modifies the association. METHODS: Urinary inorganic
arsenic concentrations among those >=12 years in the National Health and
Nutrition Examination Survey, 2005-2014 were used to assess the cross-sectional
association with serum alanine aminotransferase (ALT) levels, a marker of liver
dysfunction. We excluded high alcohol consumers (>4-5 drinks/day; n = 939),
positive hepatitis B or C (n = 2330), those missing body mass index (n = 100) and
pregnant women (n = 629) for a final sample of 8518. Arsenic was measured using
liquid chromatography coupled with mass spectrometry and ALT was measured using
standard methods. Sampling weights were used to obtain national estimates. Due to
lack of normality, estimates were log transformed and are presented as geometric
means. Logistic regression models controlling for age, sex, income, and weight
category estimate adjusted odd ratios (aOR) of elevated ALT by quartile of
arsenic and tested for effect modification by race/ethnicity and weight. Elevated
ALT was defined as >25 IU/L and >22 IU/L for boys and girls <=17 years,
respectively and >30 IU/L and >19 IU/L for men and women, respectively. RESULTS:
Among all, aOR of elevated ALT were higher among those in the highest vs. lowest
arsenic quartile (referent), 1.4 (95% confidence interval [CI]: 1.1, 1.7) with a
borderline significant interaction (p = 0.07) by race/ethnicity but not weight (p
= 0.4). In analysis stratified by race/ethnicity, aOR of elevated ALT among those
in the 4th quartile were higher among Mexican Americans, 2.0 (CI: 1.3, 3.1) and
non-Hispanic whites only, aOR 1.4 (CI: 1.1, 1.8) despite the fact that obesity
prevalence was highest among non-Hispanic blacks. CONCLUSIONS: Our findings
demonstrate a positive association between urinary arsenic exposure and risk of
NAFLD among U.S. adolescents and adults that is highest among Mexican Americans
and among those obese, regardless of race/ethnicity.
PMID- 29334961
TI - Smoke, alcohol and drug addiction and male fertility.
AB - In recent decades, the decline in human fertility has become increasingly more
worrying: while therapeutic interventions might help, they are vexing for the
couple and often burdened with high failure rates and costs. Prevention is the
most successful approach to fertility disorders in males and females alike. We
performed a literature review on three of the most common unhealthy habits -
tobacco, alcohol and drug addiction - and their reported effects on male
fertility. Tobacco smoking is remarkably common in most first-world countries;
despite a progressive decline in the US, recent reports suggest a prevalence of
more than 30% in subjects of reproductive age - a disturbing perspective, given
the well-known ill-effects on reproductive and sexual function as well as general
health. Alcohol consumption is often considered socially acceptable, but its
negative effects on gonadal function have been consistently reported in the last
30 years. Several studies have reported a variety of negative effects on male
fertility following drug abuse - a worrying phenomenon, as illicit drug
consumption is on the rise, most notably in younger subjects. While evidence in
these regards is still far from solid, mostly as a result of several confounding
factors, it is safe to assume that cessation of tobacco smoking, alcohol
consumption and recreational drug addiction might represent the best course of
action for any couple trying to achieve pregnancy.
PMID- 29334962
TI - Developing a tablet computer-based application ('App') to measure self-reported
alcohol consumption in Indigenous Australians.
AB - BACKGROUND: The challenges of assessing alcohol consumption can be greater in
Indigenous communities where there may be culturally distinct approaches to
communication, sharing of drinking containers and episodic patterns of drinking.
This paper discusses the processes used to develop a tablet computer-based
application ('App') to collect a detailed assessment of drinking patterns in
Indigenous Australians. The key features of the resulting App are described.
METHODS: An iterative consultation process was used (instead of one-off focus
groups), with Indigenous cultural experts and clinical experts. Regular (weekly
or more) advice was sought over a 12-month period from Indigenous community
leaders and from a range of Indigenous and non-Indigenous health professionals
and researchers. RESULTS: The underpinning principles, selected survey items, and
key technical features of the App are described. Features include culturally
appropriate questioning style and gender-specific voice and images; community
recognised events used as reference points to 'anchor' time periods;
'translation' to colloquial English and (for audio) to traditional language;
interactive visual approaches to estimate quantity of drinking; images of
specific brands of alcohol, rather than abstract description of alcohol type
(e.g. 'spirits'); images of make-shift drinking containers; option to estimate
consumption based on the individual's share of what the group drank. CONCLUSIONS:
With any survey platform, helping participants to accurately reflect on and
report their drinking presents a challenge. The availability of interactive,
tablet-based technologies enables potential bridging of differences in culture
and lifestyle and enhanced reporting.
PMID- 29334963
TI - Evaluating the impact of a falls prevention community of practice in a
residential aged care setting: a realist approach.
AB - BACKGROUND: Falls are a major socio-economic problem among residential aged care
(RAC) populations resulting in high rates of injury including hip fracture.
Guidelines recommend that multifactorial prevention strategies are implemented
but these require translation into clinical practice. A community of practice
(CoP) was selected as a suitable model to support translation of the best
available evidence into practice, as it could bring together like-minded people
with falls expertise and local clinical knowledge providing a social learning
opportunity in the pursuit of a common goal; falls prevention. The aims of this
study were to evaluate the impact of a falls prevention CoP on its membership;
actions at facility level; and actions at organisation level in translating falls
prevention evidence into practice. METHODS: A convergent, parallel mixed methods
evaluation design based on a realist approach using surveys, audits, observations
and semi-structured interviews. Participants were 20 interdisciplinary staff
nominating as CoP members between Nov 2013-Nov 2015 representing 13 facilities
(approximately 780 beds) of a RAC organisation. The impact of the CoP was
evaluated at three levels to identify how the CoP influenced the observed
outcomes in the varying contexts of its membership (level i.), the RAC facility
(level ii.) and RAC organisation (level iii.). RESULTS: Staff participating as
CoP members gained knowledge and awareness in falls prevention (p < 0.001)
through connecting and sharing. Strategies prioritised and addressed at RAC
facility level culminated in an increase in the proportion of residents
supplemented with vitamin D (p = 0.002) and development of falls prevention
education. At organisation level a falls policy reflecting preventative evidence
based guidelines and a new falls risk assessment procedure with aligned
management plans were written, modified and implemented. A key disenabling
mechanism identified by CoP members was limited time to engage in translation of
evidence into practice whilst enabling mechanisms included proactive behaviours
by staff and management. CONCLUSIONS: Interdisciplinary staff participating in a
falls prevention CoP gained connectivity and knowledge and were able to
facilitate the translation of falls prevention evidence into practice in the
context of their RAC facility and RAC organisation. Support from RAC
organisational and facility management to make the necessary investment in staff
time to enable change in falls prevention practice is essential for success.
PMID- 29334964
TI - Ginkgo biloba induced mood dysregulation: a case report.
AB - BACKGROUND: Impairment of cognitive function as well as negative symptom is the
major factor causing the decline of a patient's functioning in chronic stages of
schizophrenia. However, until now, there were no definite treatment options that
could effectively reduce the impairment. CASE PRESENTATION: We report a case of
mood dysregulation associated with use of Ginkgo biloba in a patient with
schizophrenia. After Ginkgo biloba was given, the patient experienced cluster
symptoms of mood dysregulation including irritability, difficulty in controlling
anger, agitation and restlessness. We estimated the possibility as "probable"
according to Naranjo scale considering circumstantial evidence. CONCLUSIONS: This
case suggests that Ginkgo biloba may have caused mood dysregulation in this
patient. Although it is generally accepted as safe, more attention should be
given to the adverse effect when treating with Ginkgo biloba.
PMID- 29334965
TI - A novel IL-1RA-PEP fusion protein alleviates blood-brain barrier disruption after
ischemia-reperfusion in male rats.
AB - BACKGROUND: Current options to treat clinical relapse in inflammatory central
nervous system (CNS) conditions such as cerebral ischemia-reperfusion injury are
limited, and agents that are more effective are required. Disruption of the blood
brain barrier is an early feature of lesion formation that correlates with
clinical exacerbation and facilitates the entry of inflammatory medium and
inflammatory cells. Interleukin-1 receptor antagonist (IL-1RA) is a naturally
occurring anti-inflammatory antagonist of the interleukin-1 (IL-1) family. The
broad-spectrum anti-inflammatory effects of IL-1RA have been investigated against
various forms of neuroinflammation. However, the effect of IL-1RA on blood-brain
barrier disruption following ischemia-reperfusion has not been reported. METHODS:
In this study, we investigated the effects of IL-1RA and a novel protein (IL-1RA
PEP) that was fused to IL-1RA with a cell penetrating peptide, on blood-brain
barrier integrity, in male rats subjected to transient middle cerebral artery
occlusion. RESULTS: After intravenous administration, IL-1RA-PEP (50 mg/kg)
penetrated cerebral tissues more effectively than IL-1RA. Moreover, it preserved
blood-brain barrier integrity, attenuated changes in expression and localization
of tight junction proteins and matrix metalloproteinases, and enhanced
angiogenesis in ischemic brain tissue. Further study suggested that the effects
of IL-1RA-PEP on preserving blood-brain barrier integrity might be closely
correlated with the p65/NF-kappaB pathway, as evidenced by the effects of the
inhibitor JSH-23. CONCLUSIONS: Collectively, our results demonstrated that IL-1RA
PEP could effectively penetrate the brain of rats with middle cerebral artery
occlusion and ameliorate blood-brain barrier disruption. This finding might
represent its novel therapeutic potential in the treatment of the cerebral
ischemia-reperfusion injury.
PMID- 29334966
TI - Atherogenic index of plasma is an effective index for estimating abdominal
obesity.
AB - BACKGROUND: The correlation between the atherogenic index of plasma (AIP) and
waist circumference (WC) remains unknown. METHODS: A total of 5351 middle-aged
men living in Southeastern China were surveyed using the random stratified
cluster sampling method. A WC of 90 cm or greater was indicative of abdominal
obesity, and AIP was calculated as follows: log [triglyceride (TG)/high-density
lipoprotein-cholesterol (HDL-C)]. RESULTS: (1) A significantly higher AIP was
observed in subjects with abdominal obesity than in those without abdominal
obesity (P < 0.001). (2) Multivariate logistic regression analysis revealed an
odds ratio of 1.93, 2.59 and 2.76 for abnormal AIP levels for the second, third
and fourth WC quartiles, respectively (all P < 0.001) compared to the first WC
quartile as a reference. (3) There was a linear correlation between WC and AIP,
and a 1.0 cm increase in WC resulted in a 0.0175 rise in AIP. For AIP
corresponding to moderate risk (0.12-0.21), WC was 85-90 cm; for AIP
corresponding to high risk (> 0.21), WC was >90 cm. CONCLUSIONS: AIP of 0.12-0.21
or >0.21 indicates a likelihood of borderline abdominal obesity or abdominal
obesity, respectively, and the combination of WC and AIP may increase the
specificity and sensitivity for detection of abdominal obesity in clinical
practice. The results suggest that AIP may be used as a reference to estimate
abdominal obesity.
PMID- 29334967
TI - Risk factors and treatment of pneumothorax secondary to granulomatosis with
polyangiitis: a clinical analysis of 25 cases.
AB - OBJECTIVES: To investigate the risk factors and treatment strategies for
pneumothorax secondary to granulomatosis with polyangiitis (GPA). METHOD:
Retrospective analysis of cases with pneumothorax secondary to GPA from our own
practice and published on literature. RESULTS: A total of 25 patients, 18 males
and 7 females, mean age 44 +/- 15.7 years, were analyzed. Diagnosis included
pneumothorax (11 cases), hydropneumothorax (n = 5), empyema (n = 8) and
hemopneumothorax (n = 1). 88% (22/25) patients showed single/multiple pulmonary/
subpleural nodules with/without cavitation on chest imaging. Erythrocyte
sedimentation rate and C-reactive protein were both elevated. Corticosteroids and
immunosuppressive agents were used in 16 cases. Five cases received steroid pulse
therapy, of which 4 patients survived. Pleural drainage was effective in some
patients. Seven patients underwent surgical operations. In the 10 fatal cases,
infection and respiratory failure were the most common cause. Lung biopsy/
autopsy showed lung/pleural necrotizing granulomatous vasculitis, breaking into
the chest cavity, pleural fibrosis, bronchial pleural fistula, etc. The mean age
in the death group was greater than the survival group (53 +/- 12.9 years vs 40.1
+/- 14.7 years, p = 0.05), the ineffective pleural drainage was also higher in
the death group (5/5 vs 0/7, p = 0.01). CONCLUSIONS: Pneumothorax was seen in the
active GPA, due to a variety of reasons, and gave rise to high fatality rate.
Aggressive treatment of GPA can improve the prognosis. Older and lack of response
for pleural drainage indicates poor prognosis.
PMID- 29334969
TI - The effects of workplace respect and violence on nurses' job satisfaction in
Ghana: a cross-sectional survey.
AB - BACKGROUND: Studies have established the negative effects of workplace disrespect
and violence on the personal and professional well-being of nurses. In spite of
this, only a few have directly investigated the effects of these issues on
nurses' job satisfaction. In Africa, research on nurses' job satisfaction
continues to focus largely on economic factors. The aim of this paper was,
therefore, to investigate the impact of the non-economic factors of workplace
violence and respect on the job satisfaction levels of nurses in Ghana. METHODS:
The study employed a cross-sectional questionnaire survey. It involved 592
qualified practising nurses working in public hospitals in Ghana. Data were
collected between September 2013 and April 2014. RESULTS: The results showed
that, overall, nurses were neither satisfied nor dissatisfied with their jobs (M
= 3.19, SD = .54). More than half (52.7%) of the participants had been abused
verbally, and 12% had been sexually harassed in the 12 months prior to the study.
The majority of nurses, however, believed they were respected at the workplace (M
= 3.77, SD = .70, Mode = 4). Multiple regression analyses showed that verbal
abuse and perceived respect were statistically significant predictors of nurses'
job satisfaction. Nurses who experienced verbal abuse and low level of respect
were more likely to report low job satisfaction scores. CONCLUSION: It is
concluded that non-financial strategies such as safe work environments which are
devoid of workplace violence may enhance nurses' job satisfaction levels. A
policy of "zero tolerance" for violence and low tolerance for disrespect could be
put in place to protect nurses and healthcare professionals in general.
PMID- 29334968
TI - Barriers and facilitators to cultural competence in rehabilitation services: a
scoping review.
AB - BACKGROUND: There is an important need to evaluate whether rehabilitation
services effectively address the needs of minority culture populations with North
America's increasingly diverse population. The objective of this paper was
therefore to review and assess the state of knowledge of barriers and
facilitators to cultural competence in rehabilitation services. METHOD: Our
scoping review focused on cultural competence in rehabilitation services.
Rehabilitation services included in this review were: audiology, speech-language
pathology, physiotherapy, and occupational therapy. A search strategy was
developed to identify relevant articles published from inception of databases
until April 2015. Titles and abstracts were screened by two independent reviewers
according to specific eligibility criteria with the use of a liberal-accelerated
approach. Full-text articles meeting inclusion criteria were then screened. Key
study characteristics were abstracted by the first reviewer, and findings were
verified by the second reviewer. RESULTS: After duplicates were removed, 4303
citations were screened. Included articles suggest that studies on cultural
competence occur most frequently in occupational therapy (n = 17), followed by
speech language pathology (n = 11), physiotherapy (n = 6), and finally audiology
(n = 1). Primary barriers in rehabilitation services include language barriers,
limited resources, and cultural barriers. Primary facilitators include cultural
awareness amongst practitioners, cultural awareness in services, and explanations
of health care systems. CONCLUSION: To our knowledge, this review is the first to
summarize barriers and facilitators to cultural competence in rehabilitation
fields. Insufficient studies were found to draw any conclusions with regards to
audiological services. Minimal perspectives based on patient/caregiver
experiences in all rehabilitation fields underscore a research gap. Future
studies should aim to explore both patient/caregiver and practitioner
perspectives as such data can help inform culturally competent practices.
PMID- 29334970
TI - Digital Media-based Health Intervention on the promotion of Women's physical
activity: a quasi-experimental study.
AB - BACKGROUND: Technological advances have caused poor mobility and lower physical
activity among humankind. This study was conducted to assess the impact of a
digital media-based (multi-media, internet, and mobile phone) health intervention
on promotion of women's physical activity. METHODS: In this quasi-experimental
study, 360 women were divided into case and control groups. The digital media
based educational intervention was conducted in two months in the case group
electronically, using mail and Internet and telephone platforms. Physical
activity was measured using International Physical Activity Questionnaire (IPAQ)
that estimated women's physical activity rate in the previous week. Data was
analyzed using descriptive and analytical statistics (ANOVA, chi-square, paired
and independent t-tests) using SPSS 20. RESULTS: The mean score of knowledge,
attitude and level of physical activity in the control group were not
significantly different before and after the intervention. While in the case
group, this difference before and after the intervention was significant (p <
0.001), and mean scores of the above-mentioned factors increased after the
intervention. CONCLUSIONS: Using innovative and digital media-based health
education can be effective in improving health-based behavior such as physical
activity. Therefore, it seems necessary to develop user-based strategies and
strengthen the behavioral change theories and hypotheses based on digital media
for effective influence on behavior. TRIAL REGISTRATION: Iranian Registry of
Clinical Trials (IRCT), IRCT20160619028529N5 . Registered December 24, 2017
[retrospectively registered].
PMID- 29334971
TI - The titanium elastic nail serves as an alternative treatment for adult proximal
radial shaft fractures: a cohort study.
AB - BACKGROUND: To investigate whether closed reduction and internal fixation (CRIF)
with titanium elastic nails (TENs) is a viable alternative treatment in proximal
radial fractures. METHODS: In Kaohsiung Veterans General Hospital, from November
2013 to April 2015, five adult male patients with forearm injuries (average age
43 years; range 35-64 years) were treated for proximal radial shaft fractures.
CRIF with TENs for radial shaft fractures was performed in these five patients.
Radiographs; range of motions; visual analog scale (VAS); quick disabilities of
the arm, shoulder, and hand (Quick DASH) questionnaire; and time to union were
evaluated in our study. RESULTS: Mean follow-up period was 30 months (range 28-36
months). Average time of radius union was 7.3 months (range 6-10 months).
Functional outcomes 1 year after operation revealed an average Quick DASH score
of 7.92 (range 4.5-25), an average VAS of 1.5 (range 1-3), and average forearm
supination and pronation of 69.2 degrees (range 45 degrees -75 degrees ) and
82.5 degrees (range 80 degrees -85 degrees ). No major complication was noted.
CONCLUSIONS: CRIF with TEN for adult proximal radial fractures is a method to
avoid extensive exposure or nerve injury during ORIF, especially in multiple
trauma patients who require short operative time, uremia patients with
ipsilateral forearm AV shunt, severe soft tissue swelling due to direct muscle
contusion or strong muscularity before surgery, extensive radial fracture, and
those in pursuit of cosmetic outcomes.
PMID- 29334972
TI - Community readiness assessment for obesity research: pilot implementation of the
Healthier Families programme.
AB - BACKGROUND: This article reports on the development of a systematic approach to
assess for community readiness prior to implementation of a behavioural
intervention for childhood obesity. Using the Consolidated Framework for
Implementation Research (CFIR), we developed research tools to evaluate local
community centres' organisational readiness and their capacity to implement the
intervention. METHODS: Four community Parks and Recreation centres from different
states expressed interest in piloting an approach for dissemination and
implementation of an evidence-based obesity prevention program for families with
young children (Healthier Families). We conducted a mixed methods pre
implementation evaluation using the CFIR to evaluate the alignment of
organisational priorities with the Healthier Families programme. Written surveys
assessed organisational readiness for change amongst organisational leaders,
recreation programmers, and staff (N = 25). Key informant interviews were
conducted among staff to assess organisational readiness and with community
members to assess community readiness (N = 64). Surveys were analysed with
univariate statistics. Interviews were transcribed, coded and analysed using
inductive and deductive methods of analysis. RESULTS: Mixed-methods analysis led
to the identification of three key domains on which to assess the organisational
readiness to adopt a childhood obesity intervention, namely the physical
infrastructure, the knowledge infrastructure, and the social infrastructure. The
most critical measure of compatibility was the social infrastructure, since
obstacles in the knowledge and physical infrastructures could be overcome by the
strength of social resources, including the staff's ingenuity and commitment to a
healthier community. This approach guided an assessment of organisational
readiness prior to community organisations adopting and preparing to disseminate
an obesity prevention community-based program in a wide-range of social and
environmental contexts. CONCLUSIONS: Using a comprehensive pre-implementation
assessment of the knowledge, physical and social infrastructures in a community
is an essential step in effective dissemination for community-based behavioural
interventions. Our research found that, when evaluating readiness and alignment,
a responsive social infrastructure could provide the capacity to overcome
potential barriers to implementation in either the knowledge or physical
infrastructures.
PMID- 29334973
TI - Options for reducing HIV transmission related to the dead space in needles and
syringes.
AB - BACKGROUND: When shared by people who inject drugs, needles and syringes with
different dead space may affect the probability of HIV and hepatitis C virus
(HCV) transmission differently. METHODS: We measured dead space in 56 needle and
syringe combinations obtained from needle and syringe programs across 17
countries in Europe and Asia. We also calculated the amounts of blood and HIV
that would remain in different combinations following injection and rinsing.
RESULTS: Syringe barrel capacities ranged from 0.5 to 20 mL. Needles ranged in
length from 8 to 38 mm. The average dead space was 3 MUL in low dead space
syringes with permanently attached needles, 13 MUL in high dead space syringes
with low dead space needles, 45 MUL in low dead space syringes with high dead
space needles, and 99 MUL in high dead space syringes with high dead space
needles. Among low dead space designs, calculated volumes of blood and HIV viral
burden were lowest for low dead space syringes with permanently attached needles
and highest for low dead space syringes with high dead space needles. CONCLUSION:
The dead space in different low dead space needle and syringe combinations varied
substantially. To reduce HIV transmission related to syringe sharing, needle and
syringe programs need to combine this knowledge with the needs of their clients.
PMID- 29334974
TI - Prevalence of dysmenorrhea and predictors of its pain intensity among Palestinian
female university students.
AB - BACKGROUND: Few studies on gynaecological problems of young females in Arab
countries were published. The aim of this study was to determine the prevalence
of dysmenorrhea and predictors of its pain among university students in
Palestine. METHODS: A cross - sectional study was carried out on a randomly
selected sample of An-Najah National University female students. A pre-designed
questionnaire, which included questions regarding menstrual cycle, pain during
menstruation, life style, nutritional habits, and symptoms associated with
menstrual pain, was used. Pain intensity was measured using visual analogue
scale. RESULTS: A total of 956 female students were involved in the study. Of the
total study sample, 846 (85.1%) reported having pain during menstruation; i.e.
dysmenorrhea. Dysmenorrhea was significantly [(p = 0.027); OR = 1.5, 95% CI (1.05
2.19)] associated with age at menarche. The mean score of pain among dysmenorrhic
females was 6.79 +/- 2.64. The majority (654; 80.34%) of dysmenorrhic females
reported having moderate/ severe pain. Univariate analysis using Chi-square test
for factors associated with moderate/severe pain among dysmenorrhic females were
irregular cycle [(p = 0.015); OR = 1.57, 95% CI = (1.09-2.30)], skipping
breakfast [(p < 0.001); OR = 1.93, 95% CI = (1.33-2.79)], academic specialization
[(p = 0.03; OR = 2.2, 95% CI = (1.21-3.98)] for medical specialization with
reference to students in humanities), high stress level [(p = 0.036; OR = 1.53,
95% CI = (1.03-2.28)], and living in dormitories [(p = 0.034); OR = 1.72, 95% CI
= (1.04-2.86)]. Multivariate analysis using binary logistic regression enter
method showed that medical specialization [(p = 0.045); OR = 1.92, 95% CI = (1.02
3.64)] for medical students with reference to students in humanities), skipping
breakfast [(p = 0.001); OR = 1.96, 95% CI = (1.35-2.86)], and irregular cycle [(p
= 0.022); OR = 1.56, 95% CI = (1.07-2.29)] were the only significant predictors
of moderate/severe dysmenorrhic pain. CONCLUSION: There is a high proportion of
dysmenorrhea among Palestinian female university students. Skipping breakfast was
the strongest predictor for moderate/severe dysmenorrhea. Increased awareness
regarding factors that might influence the intensity of dysmenorrhic pain is
needed.
PMID- 29334976
TI - Plants traditionally used to make Cantonese slow-cooked soup in China.
AB - BACKGROUND: Lao huo liang tang (Cantonese slow-cooked soup, CSCS) is popular in
Guangdong, China, and is consumed by Cantonese people worldwide as a delicious
appetizer. Because CSCS serves as an important part of family healthcare,
medicinal plants and plant-derived products are major components of CSCS.
However, a collated record of the diverse plant species and an ethnobotanical
investigation of CSCS is lacking. Because of globalization along with a renewed
interest in botanical and food therapy, CSCS has attracted a growing attention in
soup by industries, scientists, and consumers. This study represents the first
attempt to document the plant species used for CSCS in Guangdong, China, and the
associated ethnomedical function of plants, including their local names, part(s)
used, flavors, nature, preparation before cooking, habitats, and conservation
status. METHODS: In 2014-2017, participatory approaches, open-ended
conversations, and semi-structured interviews were conducted with 63 local people
and 48 soup restaurant owners (111 interviews) to better understand the
biocultural context of CSCS, emphasizing ethnobotanical uses of plants in
Guangdong Province, China. Product samples and voucher specimens were collected
for taxonomic identification. Mention Index (QI), frequency of use index (FUI),
and economic index (EI) were adopted to evaluate the significance of each plant
in the food supply. RESULTS: A total of 97 plant species belonging to 46 families
and 90 genera were recorded as having been used in CSCS in the study area.
Recorded menus consisted of one or several plant species, with each one used for
different purposes. They were classified into 11 functions, with clearing heat
being the most common medicinal function. Of the 97 species, 19 grew only in the
wild, 8 species were both wild and cultivated, and 70 species were cultivated.
Roots and fruits were the most commonly used plant parts in the preparation of
CSCS. According to the national evaluation criteria, six of these species are
listed on "China's red list" including two endangered, two critically endangered,
one near-threatened, and one vulnerable species. The QI, FUI, and EI of the 97
species in the study varied between 0.09 and 1, 0.23 and 9.95, and 0.45 and 6.58,
respectively. CONCLUSIONS: As an important part of Cantonese culture, CSCS has
been popularized as a local cuisine with a healthcare function. CSCS also
reflects the plant species richness and cultural diversity of Guangdong Province.
Future research on the safety and efficacy of CSCS as well as on ecological and
cultural conservation efforts is needed for the sustainable growth of China's
botanical and medicinal plant industry.
PMID- 29334975
TI - Molecular characterization of duck enteritis virus UL41 protein.
AB - BACKGROUND: Duck enteritis virus (DEV) belongs to the subfamily
Alphaherpesvirinae, and information on the DEV UL41 gene is limited. METHODS: The
DEV UL41 gene was cloned into the pET32a(+) vector and expressed in a prokaryotic
expression system. Antiserum was raised against a bacterially expressed UL41-His
fusion protein for further experiments. Transcription was quantified and UL41
protein expression levels were determined in DEV-infected cells at different time
points by RT-qPCR and western blotting, respectively. DEV virions were purified
by sucrose gradient centrifugation and analyzed by mass spectrometry to identify
protein content. We confirmed the DEV UL41 gene kinetic class using a
pharmacological test. IFA was used to analyze the intracellular localization of
pUL41. RESULTS: The recombinant expression plasmid, pET-32a(+)-UL41, which highly
expresses a 76.0 kDa fusion protein, was constructed and expressed in E. coli
BL21 (DE3) after induction with 0.2 mM IPTG at 30 degrees C for 10 h, generating
a specific mouse anti-UL41 protein polyclonal antibody. RT-qPCR and western blot
analyses revealed that the UL41 transcript number peaked at 36 hpi, and peak
protein expression occurred at 48 hpi. The pharmacological test showed that UL41
was a gamma2 gene. Mass spectrometry analysis showed that pUL41 was a virion
component. IFA results revealed that pUL41 was localized throughout DEV-infected
cells but only localized to the cytoplasm of transfected cells. DEV pUL47
translocated pUL41 to the nuclei of DEF cells; this translocation was dependent
on predicted pUL47 NLS signals (40-50 aa and 768-777 aa). CONCLUSIONS: DEV UL41
is a gamma2 gene that encodes a virion structural protein, pUL41 localizes
throughout DEV-infected cells but only localizes to the cytoplasm of transfected
cells. pUL41 cannot autonomously localize to the nucleus, as this nuclear
localization is dependent on predicted DEV pUL47 NLS signals (40-50 aa and 768
777 aa).
PMID- 29334977
TI - Ethnoecology of the interchange of wild and weedy plants and mushrooms in
Phurepecha markets of Mexico: economic motives of biotic resources management.
AB - BACKGROUND: Interactions between societies and nature are regulated by complex
systems of beliefs, symbolism, customs, and worldviews (kosmos), ecological
knowledge (corpus), and management strategies and practices (praxis), which are
constructed as product of experiences and communication of people throughout
time. These aspects influence social relations, life strategies, and cultural
identity, and all of them in turn influence and are influenced by local and
regional patterns of interchange. In this study, we analyze the interchange of
wild and weedy plants and mushrooms in traditional markets of the Phurepecha
region of Mexico. Particularly, the social relations constructed around the
interchange of these products; how knowledge, cultural values, and ecological
factors influence and are influenced by interchange; and how all these factors
influence the type and intensity of biotic resources management. METHODS: We
studied three main traditional markets of the Phurepecha region of Michoacan,
Mexico, through 140 visits to markets and 60 semi-structured interviews to
sellers of wild and weedy plants and mushrooms. In nearly 2 years, we carried out
80 visits and 30 interviews in the "Barter Market", 20 visits and 15 interviews
in the "Phurepecha Tianguis", and 40 visits and 15 interviews to the "Municipal
Market". We documented information about the spaces of interchange that form the
markets, the types of interchange occurring there, the cultural and economic
values of the resources studied, the environmental units that are sources of such
resources, the activities associated to resources harvesting and, particularly,
the management techniques practiced to ensure or increase their availability. We
analyzed the relations between the amounts of products interchanged, considered
as pressures on the resources; the perception of their abundance or scarcity,
considered as the magnitude of risk in relation to the pressures referred to; and
the management types as response to pressures and risk. RESULTS: We recorded 38
species of wild and weedy plants and 15 mushroom species interchanged in the
markets. We characterized the spaces of interchange, the interchange types, and
social relations among numerous Phurepecha communities which maintain the main
features of pre-Columbian markets. The products analyzed are differentially
valued according to their role in people's life, particularly food, medicine,
rituals, and ornamental purposes. The highest cultural values were identified in
multi-purpose plant and mushroom resources and, outstandingly, in ornamental and
ritual plants. In markets, women are the main actors and connectors of the
regional households' activities of use and management of local resources and
ecosystems. The interrelationships between worldviews, knowledge, and practices
are visible through the interchange of the products analyzed, including the types
of environments comprised in communitarian territories, agricultural calendars,
and feasts. Those plants and mushrooms are highly valued but relatively scarce
according to the demand on them receiving special attention and management
practices directed to ensure or increase their availability. With the exception
of most mushrooms and ornamental and ritual plants, which have high economic and
cultural values, there are those that are relatively scarce and under high risk,
but are obtained through simple gathering from the wild. CONCLUSIONS: Traditional
markets are crucial part of the subsistence strategy of Phurepecha people based
on the multiple use of resources and ecosystems at the local and regional levels.
The markets influence social relations, cultural identity, and preservation of
traditional knowledge and biodiversity. In general, the demand of products in
markets enhances innovation and practices for ensuring or increasing their
availability, particularly those that are naturally scarce. However, it was
notorious that, althoug mushrooms and ritual plants have high demand and value in
markets, most of them are obtained by simple gathering.
PMID- 29334978
TI - Plasma virome of cattle from forest region revealed diverse small circular ssDNA
viral genomes.
AB - BACKGROUND: Free-range cattle are common in the Northeast China area, which have
close contact with farmers and may carry virus threatening to cattle and farmers.
METHODS: Using viral metagenomics we analyzed the virome in plasma samples
collected from 80 cattle from the forested region of Northeast China. RESULTS:
The virome of cattle plasma is composed of the viruses belonging to the families
including Parvoviridae, Papillomaviridae, Picobirnaviridae, and divergent viral
genomes showing sequence similarity to circular Rep-encoding single stranded
(CRESS) DNA viruses. Five such CRESS-DNA genomes were full characterized, with
Rep sequences related to circovirus and gemycircularvirus. Three bovine
parvoviruses belonging to two different genera were also characterized.
CONCLUSION: The virome in plasma samples of cattle from the forested region of
Northeast China was revealed, which further characterized the diversity of
viruses in cattle plasma.
PMID- 29334979
TI - Measuring spatial accessibility to healthcare services with constraint of
administrative boundary: a case study of Yanqing District, Beijing, China.
AB - BACKGROUND: The two-step floating catchment area (2SFCA) method, which is one of
the most widely used methods for measuring healthcare spatial accessibility,
defines the catchment area of each facility as the area within a certain distance
from the facility. However, in some cases, the service utilization behavior is
constrained by administrative boundaries, therefore the definition of catchment
area within a certain distance may be inappropriate. METHODS: In this study, we
aim to propose a modification of the 2SFCA method for measuring spatial
accessibility to healthcare services in a system constrained by administrative
boundaries. The proposed method defines the catchment areas of healthcare
facilities within certain administrative units. The method is applied in a case
study of the healthcare services in Yanqing District of Beijing, China. Three
types of healthcare facilities, including general hospitals, community healthcare
centers and stations, are included. RESULTS: Based on the sensitivity analysis of
the distance-decay parameter beta, result of the beta = 1 scenario is relatively
appropriate and is utilized for further analysis. The difference between spatial
accessibility with or without constraint of administrative boundary is relatively
significant. The results of the proposed model show that the village-level
spatial accessibility to healthcare services shows a significant disparity, and
the uneven distribution of general hospitals is the main cause. CONCLUSIONS: The
constraint of administrative boundary has a significant impact on healthcare
accessibility, which verifies the validity of the modification proposed by this
study in empirical studies. The empirical results also lead to policy
recommendations to improve healthcare equity in the study area. At the town
level, the improvement of equity in healthcare accessibility could be achieved in
two ways. First, the sizes of community healthcare centers in towns with small
accessibility scores should be expanded. Second, new general hospitals can be
built in the eastern part of Yanqing District. Within each town, to improve the
equity in healthcare accessibility, community healthcare stations should be
expanded or newly built in the periphery villages.
PMID- 29334980
TI - Reoperation for a giant arch anastomotic pseudoaneurysm eleven years after total
arch replacement with island reconstruction.
AB - BACKGROUND: The long-term effects of some surgical treatment procedures of arch
replacement for aortic dissection or aortic aneurysm are unknown. CASE
PRESENTATION: The present study reports the case of a 68-year-old man admitted to
our hospital for aortic arch anastomotic pseudoaneurysm with concomitant aortic
root enlargement and coronary artery stenosis. Eleven years ago, at the age of 56
years, he underwent total arch replacement with island reconstruction for chronic
aortic dissection. We performed a second total arch replacement, aortic root
replacement, and coronary artery bypass, using a cardiopulmonary bypass with
cannulation through the right subclavian artery, femoral artery, and femoral vein
prior to re-sternotomy. We also used selective cerebral perfusion.
Postoperatively, the patient temporarily required reintubation; however, he was
discharged in good condition on the fiftieth postoperative day. CONCLUSIONS: This
case suggests that island reconstruction has the potential to cause arch
anastomotic pseudoaneurysms, particularly after a long postoperative period.
PMID- 29334981
TI - Production of highly and broad-range specific monoclonal antibodies against
hemagglutinin of H5-subtype avian influenza viruses and their differentiation by
mass spectrometry.
AB - BACKGROUND: The highly pathogenic avian influenza viruses of the H5 subtype, such
as the H5N1 viral strains or the novel H5N8 and H5N2 reassortants, are of both
veterinary and public health concern worldwide. To combat these viruses,
monoclonal antibodies (mAbs) against H5 hemagglutinin (HA) play a significant
role. These mAbs are effective diagnostic and therapeutic agents and powerful
tools in vaccine development and basic scientific research. The aim of this study
was to obtain diagnostically valuable mAbs with broad strain specificity against
H5-subtype AIVs. RESULTS: We applied the hybridoma method to produce anti-HA
mAbs. The cloning and screening procedures resulted in the selection of 7 mouse
hybridoma cell lines and their respective antibody clones. Preliminary
immunoreactivity studies showed that these newly established mAbs, all of the
IgG1 isotype, had high specificity and broad-range activities against the H5 HAs.
However, these studies did not allow for a clear distinction among the selected
antibodies and mAb-secreting hybridoma clones. To differentiate the analyzed mAbs
and determine the exact number of hybridoma clones, peptide mapping of the Fc and
Fab fragments was performed using a Matrix-Assisted Laser Desorption Ionization
Time of Flight (MALDI-TOF/TOF) mass spectrometer. Detailed analyses of the
acquired MS and MS/MS spectra confirmed that the Fc fragments constituted highly
conserved species- and isotype-immunoglobulin components, whereas the Fab
fragments exhibited considerable variation in the sequences that determine
antibody specificity. This approach enabled unambiguous characterization of the
selected mAbs according to their peptide composition. As a result, 6 different
clones were distinguished. CONCLUSIONS: Our work provided a unique panel of anti
H5 HA mAbs, which meets the demand for novel, high-specificity analytical tools
for use in serologic surveillance. Applications of these mAbs in areas other than
diagnostics are also possible. Moreover, we demonstrated for the first time that
peptide mapping of antibody fragments with mass spectrometry is an efficient
method for the differentiation of antibody clones and relevant antibody-producing
cell lines. The method may be successfully used to characterize mAbs at the
protein level.
PMID- 29334982
TI - Genome-wide identification, characterization and classification of ionotropic
glutamate receptor genes (iGluRs) in the malaria vector Anopheles sinensis
(Diptera: Culicidae).
AB - BACKGROUND: Ionotropic glutamate receptors (iGluRs) are conserved ligand-gated
ion channel receptors, and ionotropic receptors (IRs) were revealed as a new
family of iGluRs. Their subdivision was unsettled, and their characteristics are
little known. Anopheles sinensis is a major malaria vector in eastern Asia, and
its genome was recently well sequenced and annotated. METHODS: We identified
iGluR genes in the An. sinensis genome, analyzed their characteristics including
gene structure, genome distribution, domains and specific sites by bioinformatic
methods, and deduced phylogenetic relationships of all iGluRs in An. sinensis,
Anopheles gambiae and Drosophila melanogaster. Based on the characteristics and
phylogenetics, we generated the classification of iGluRs, and comparatively
analyzed the intron number and selective pressure of three iGluRs subdivisions,
iGluR group, Antenna IR and Divergent IR subfamily. RESULTS: A total of 56 iGluR
genes were identified and named in the whole-genome of An. sinensis. These genes
were located on 18 scaffolds, and 31 of them (29 being IRs) are distributed into
10 clusters that are suggested to form mainly from recent gene duplication. These
iGluRs can be divided into four groups: NMDA, non-NMDA, Antenna IR and Divergent
IR based on feature comparison and phylogenetic analysis. IR8a and IR25a were
suggested to be monophyletic, named as Putative in the study, and moved from the
Antenna subfamily in the IR family to the non-NMDA group as a sister of
traditional non-NMDA. The generated iGluRs of genes (including NMDA and
regenerated non-NMDA) are relatively conserved, and have a more complicated gene
structure, smaller omega values and some specific functional sites. The iGluR
genes in An. sinensis, An. gambiae and D. melanogaster have amino-terminal domain
(ATD), ligand binding domain (LBD) and Lig_Chan domains, except for IR8a that
only has the LBD and Lig_Chan domains. However, the new concept IR family of
genes (including regenerated Antenna IR, and Divergent IR), especially for
Divergent IR are more variable, have a simpler gene structure (intron loss
phenomenon) and larger omega values, and lack specific functional sites. These IR
genes have no other domains except for Antenna IRs that only have the Lig_Chan
domain. CONCLUSIONS: This study provides a comprehensive information framework
for iGluR genes in An. sinensis, and generated the classification of iGluRs by
feature and bioinformatics analyses. The work lays the foundation for further
functional study of these genes.
PMID- 29334983
TI - An individually tailored family-centered intervention for pediatric obesity in
primary care: study protocol of a randomized type II hybrid effectiveness
implementation trial (Raising Healthy Children study).
AB - BACKGROUND: Pediatric obesity is a multi-faceted public health concern that can
lead to cardiovascular diseases, cancers, and early mortality. Small changes in
diet, physical activity, or BMI can significantly reduce the possibility of
developing cardiometabolic risk factors. Family-based behavioral interventions
are an underutilized, evidence-based approach that have been found to
significantly prevent excess weight gain and obesity in children and adolescents.
Poor program availability, low participation rates, and non-adherence are noted
barriers to positive outcomes. Effective interventions for pediatric obesity in
primary care are hampered by low family functioning, motivation, and adherence to
recommendations. METHODS: This (type II) hybrid effectiveness-implementation
randomized trial tests the Family Check-Up 4 Health (FCU4Health) program, which
was designed to target health behavior change in children by improving family
management practices and parenting skills, with the goal of preventing obesity
and excess weight gain. The FCU4Health is assessment driven to tailor services
and increase parent motivation. A sample of 350 families with children aged 6 to
12 years who are identified as overweight or obese (BMI >= 85th percentile for
age and gender) will be enrolled at three primary care clinics [two Federally
Qualified Healthcare Centers (FQHCs) and a children's hospital]. All clinics
serve predominantly Medicaid patients and a large ethnic minority population,
including Latinos, African Americans, and American Indians who face disparities
in obesity, cardiometabolic risk, and access to care. The FCU4Health will be
coordinated with usual care, using two different delivery strategies: an embedded
approach for the two FQHCs and a referral model for the hospital-based clinic. To
assess program effectiveness (BMI, body composition, child health behaviors,
parenting, and utilization of support services) and implementation outcomes (such
outcomes as acceptability, adoption, feasibility, appropriateness, fidelity, and
cost), we use a multi-method and multi-informant assessment strategy including
electronic health record data, behavioral observation, questionnaires,
interviews, and cost capture methods. DISCUSSION: This study has the potential to
prevent excess weight gain, obesity, and health disparities in children by
establishing the effectiveness of the FCU4Health and collecting information
critical for healthcare decision makers to support sustainable implementation of
family-based programs in primary care. TRIAL REGISTRATION: NCT03013309
ClinicalTrials.gov.
PMID- 29334984
TI - New insights into ANGPLT3 in controlling lipoprotein metabolism and risk of
cardiovascular diseases.
AB - Dyslipidemia, characterized by elevation of plasma low density lipoprotein
cholesterol (LDL-C), triglyceride (TG) and reduction of plasma high density
lipoprotein cholesterol (HDL-C), has been verified as a causal risk factor for
cardiovascular diseases (CVD), leading to a high mortality rate in general
population. It is important to understand the molecular metabolism underlying
dyslipidemia in order to reduce the risk and to develop effective therapeutic
approaches against CVD. ANGPTL3 (human) or Angptl3 (mouse), one member of the
angiopoietin-like protein (ANGPTL) family, has been identified as an important
regulator of lipid metabolism by inhibiting LPL and EL activity. Results have
demonstrated that inactivation of Angptl3 in mice could obviously reduce the
level of TG, LDL-C and the atherosclerotic lesion size, leading to a lower risk
for dyslipidemia and CVD. Additionally, in humans, carriers with homozygous LOF
mutations in ANGPTL3 have lower plasma LDL-C, TG levels and lower risk of
atherosclerosis compared to the non-carriers. Here, we collect the latest data
and results, giving a new insight into the important role of ANGPTL3 in
controlling lipoprotein metabolism. Finally, we introduce two update reports on
the antisense oligonucleotide and monoclonal antibody-based inactivation of
ANGPTL3 in human clinical trials, to identify that ANGPTL3 could be a novel and
effective target for the treatment of dyslipidemia and CVD.
PMID- 29334985
TI - Role of sleep duration and sleep-related problems in the metabolic syndrome among
children and adolescents.
AB - BACKGROUND: There is increasing recognition that sleep is a risk factor for
metabolic syndrome (MetS). The aim of the present study was to analyze the
relationship between self-reported sleep duration, sleep-related problems and the
presence of MetS in children and adolescents from Bogota, D.C., Colombia.
METHODS: This is a cross-sectional analysis from the FUPRECOL study (2014-15).
Participants included 2779 (54.2% girls) youth from Bogota (Colombia). MetS was
defined as the presence of >=3 of the metabolic abnormalities (hyperglycemia,
hypertriglyceridemia, low high-density lipoprotein cholesterol [HDL-c],
hypertension, and increased waist circumference) according to the criteria of de
Ferranti/Magge and colleges. Self-reported sleep duration and sleep-related
problems were assessed with the BEARS questionnaire. RESULTS: Logistic regression
analysis showed that boys who meet recommended duration of sleep had a decreased
risk of elevated blood glucose levels (Odds Ratio [OR] = 0.71, 95%CI [0.40-0.94];
p = 0.031) compared to boys who have short-long sleep duration. Also, compared to
young without sleep problems, excessive sleepiness during the day was related to
low HDL-c levels in boys (OR = 1.36, 95%CI [1.02-1.83]; p = 0.036) and high
triglyceride levels in girls (OR = 1.28, 95%CI [1.01-1.63]; p = 0.045). Girls
with irregular sleep patterns had decreased HDL-c levels (OR = 0.71, 95%CI [0.55
0.91]; p = 0.009). CONCLUSIONS: Recommended sleep duration was associated with a
decreased risk of elevated fasting glucose levels in boys, and sleep problems was
related to lower HDL-c in girls and higher triglyceride levels in boys. These
findings suggested the clinical importance of improving sleep hygiene to reduce
metabolic risk factors in children and adolescents.
PMID- 29334987
TI - Representative survey on idiopathic environmental intolerance attributed to
electromagnetic fields in Taiwan and comparison with the international
literature.
AB - BACKGROUND: Electromagnetic hypersensitivity refers to health effects attributed
to electromagnetic fields (EMF) exposure and has been formally named "idiopathic
environmental intolerance attributed to electromagnetic fields" (IEI-EMF) by the
World Health Organization. Because of the growing use of cell phones, IEI-EMF has
become a global public health concern. A survey in 2007 in Taiwan showed that the
prevalence rate of IEI-EMF was 13.3%, which is higher than rates in studies
conducted previously. The survey also found that the rate was higher in women.
METHODS: To evaluate whether the prevalence rate of IEI-EMF is increasing and to
verify the higher risk in women, we conducted a nationwide questionnaire survey
using the same methods as the 2007 survey to assess the change in the prevalence
rate of IEI-EMF in Taiwan. We also conducted a review of the literature and a
meta-analysis to evaluate the changes in the prevalence rate around the world.
RESULTS: On the basis of the representative sample of 3303 participants, we found
that the prevalence rate of IEI-EMF in Taiwan declined from 13.3% to 4.6% over a
period of 5 years. The literature review also found the prevalence rates in other
countries to be decreasing, instead of increasing as predicted previously. The
meta-analysis of the data from the literature showed that women are more likely
to have IEI-EMF than men, with an odds ratio of 1.19 (95% confidence interval:
1.01-1.40). CONCLUSIONS: We found the prevalence rate of IEI-EMF has been
declining, instead of increasing as predicted previously. Women are more likely
to report having IEI-EMF than men. Further studies to explore the causes leading
to the declines may help the public, scientific community, and government deal
with idiopathic intolerance to other environmental exposures.
PMID- 29334986
TI - Bridging pro-inflammatory signals, synaptic transmission and protection in spinal
explants in vitro.
AB - Multiple sclerosis is characterized by tissue atrophy involving the brain and the
spinal cord, where reactive inflammation contributes to the neurodegenerative
processes. Recently, the presence of synapse alterations induced by the
inflammatory responses was suggested by experimental and clinical observations,
in experimental autoimmune encephalomyelitis mouse model and in patients,
respectively. Further knowledge on the interplay between pro-inflammatory agents,
neuroglia and synaptic dysfunction is crucial to the design of unconventional
protective molecules. Here we report the effects, on spinal cord circuits, of a
cytokine cocktail that partly mimics the signature of T lymphocytes sub
population Th1. In embryonic mouse spinal organ-cultures, containing neuronal
cells and neuroglia, cytokines induced inflammatory responses accompanied by a
significant increase in spontaneous synaptic activity. We suggest that cytokines
specifically altered signal integration in spinal networks by speeding the decay
of GABAA responses. This hypothesis is supported by the finding that synapse
protection by a non-peptidic NGF mimetic molecule prevented both the changes in
the time course of GABA events and in network activity that were left unchanged
by the cytokine production from astrocytes and microglia present in the cultured
tissue. In conclusion, we developed an important tool for the study of synaptic
alterations induced by inflammation, that takes into account the role of neuronal
and not neuronal resident cells.
PMID- 29334988
TI - Epidermal Wnt signalling regulates transcriptome heterogeneity and proliferative
fate in neighbouring cells.
AB - BACKGROUND: Canonical Wnt/beta-catenin signalling regulates self-renewal and
lineage selection within the mammalian epidermis. Although the transcriptional
response of keratinocytes that receive a Wnt signal is well characterized, little
is known about the mechanism by which keratinocytes in proximity to the Wnt
receiving cell are co-opted to undergo a change in cell fate. RESULTS: To address
this, we perform single-cell RNA-sequencing on mouse keratinocytes co-cultured
with and without beta-catenin-activated neighbouring cells. We identify five
distinct cell states in cultures that had not been exposed to the beta-catenin
stimulus and show that the stimulus redistributes wild-type subpopulation
proportions. Using temporal single-cell analysis, we reconstruct the cell fate
change induced by Wnt activation from neighbouring cells. Gene expression
heterogeneity is reduced in neighbouring cells and this effect is most dramatic
for protein synthesis-associated genes. Changes in gene expression are
accompanied by a shift to a more proliferative stem cell state. By integrating
imaging and reconstructed sequential gene expression changes during the state
transition we identify transcription factors, including Smad4 and Bcl3, that are
responsible for effecting the transition in a contact-dependent manner.
CONCLUSIONS: Our data indicate that non-cell autonomous Wnt/beta-catenin
signalling decreases transcriptional heterogeneity. This furthers our
understanding of how epidermal Wnt signalling orchestrates regeneration and self
renewal.
PMID- 29334989
TI - Implantation of a 3D-printed titanium sternum in a patient with a sternal tumor.
AB - BACKGROUND: Primary malignant or metastatic sternal tumors are uncommon. A
subtotal or total sternectomy can offer a radical form of treatment. The issue is
to restore the structural integrity of the chest wall. CASE PRESENTATION: We
report the implantation of an individualized 3D-printed titanium sternum in a
patient with a sternal tumor. CONCLUSIONS: We believe that tridimensional print
technologies may also change the strategy of chest wall reconstruction.
PMID- 29334990
TI - Performance evaluation of existing immunoassays for Clonorchis sinensis infection
in China.
AB - BACKGROUND: Clonorchiasis ranks among the most important food-borne parasitic
diseases in China. However, due to low compliance to traditional fecal
examination techniques in the general population and medical personnel,
immunodiagnosis is expected. This study evaluated, in parallel, the performance
of four immunodiagnostic kits detecting clonorchiasis in China. RESULTS: A bank
with 475 sera was established in this study. Except for the low performance of
the kit detecting IgM, the other three kits detecting IgG showed sensitivities
ranging from 81.51% (194/238) to 99.16% (236/238). Higher sensitivity was
presented in heavy infection intensity [89.47% (68/76) to 100% (76/76)]. Among
the four kits, the overall specificity varied from 73.42% (174/237) to 87.34%
(207/237). It was observed that the specificity was lower in the sera of the
participants living in clonorchiasis-endemic areas but without any parasite
infection [67.5% (81/120) to 90% (108/120)], as compared to those from the non
endemic area [94% (47/50) to 98% (49/50)]. The cross-reaction rate varied from
14.93% (10/67) to 31.34% (21/67). Youden's index was -0.022, 0.689, 0.726, and
0.802 for kits T1, T2, T3 and T4, respectively. Repeatability was high in all
four kits. CONCLUSIONS: Three immunodiagnosis kits targeting IgG antibody had
high performance on detecting chronic Clonorchis sinensis infection, but that
detecting IgM antibody had not. The kits detecting IgG antibody also showed high
sensitivity in heavy infection intensity. Research on immunological diagnosis of
clonorchiasis is expected to be strengthened to improve the sensitivity in light
infection and specificity.
PMID- 29334992
TI - The efficacy of a multimodal physical activity intervention with supervised
exercises, health coaching and an activity monitor on physical activity levels of
patients with chronic, nonspecific low back pain (Physical Activity for Back Pain
(PAyBACK) trial): study protocol for a randomised controlled trial.
AB - BACKGROUND: Physical activity plays an important role in the management of
chronic low back pain (LBP). Engaging in an active lifestyle is associated with a
better prognosis. Nevertheless, there is evidence to suggest that patients with
chronic LBP are less likely to meet recommended physical activity levels.
Furthermore, while exercise therapy has been endorsed by recent clinical practice
guidelines, evidence from systematic reviews suggests that its effect on pain and
disability are at best moderate and not sustained over time. A limitation of
current exercises programmes for chronic LBP is that these programmes are not
designed to change patients' behaviour toward an active lifestyle. Therefore, we
will investigate the short- and long-term efficacy of a multimodal intervention,
consisting of supervised exercises, health coaching and use of an activity
monitor (i.e. Fitbit Flex) compared to supervised exercises plus sham coaching
and a sham activity monitor on physical activity levels, pain intensity and
disability, in patients with chronic, nonspecific LBP. METHODS: This study will
be a two-group, single-blind, randomised controlled trial. One hundred and sixty
adults with chronic, nonspecific LBP will be recruited. Participants allocated to
both groups will receive a group exercise programme. In addition, the
intervention group will receive health coaching sessions (i.e. assisting the
participants to achieve their physical activity goals) and an activity monitor
(i.e. Fitbit Flex). The participants allocated to the control group will receive
sham health coaching (i.e. encouraged to talk about their LBP or other problems,
but without any therapeutic advice from the physiotherapist) and a sham activity
monitor. Outcome measures will be assessed at baseline and at 3, 6 and 12 months
post randomisation. The primary outcomes will be physical activity, measured
objectively with an accelerometer, as well as pain intensity and disability at 3
months post randomisation. Secondary outcomes will be physical activity, pain
intensity and disability at 6 and 12 months post randomisation as well as other
self-report measures of physical activity and sedentary behaviour, depression,
quality of life, pain self-efficacy and weight-related outcomes at 3, 6, and 12
months post randomisation. DISCUSSION: This study is significant as it will be
the first study to investigate whether a multimodal intervention designed to
increase physical activity levels reduces pain and disability, and increases
physical activity levels compared to a control intervention in patients with
chronic LBP. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03200509 . Registered
on 28 June 2017.
PMID- 29334991
TI - Role of the nervous system in cancer metastasis.
AB - Cancer remains as one of the leading cause of death worldwide. The development of
cancer involves an intricate process, wherein many identified and unidentified
factors play a role. Although most studies have focused on the genetic
abnormalities which initiate and promote cancer, there is overwhelming evidence
that tumors interact within their environment by direct cell-to-cell contact and
with signaling molecules, suggesting that cancer cells can influence their
microenvironment and bidirectionally communicate with other systems. However,
only in recent years the role of the nervous system has been recognized as a
major contributor to cancer development and metastasis. The nervous system
governs functional activities of many organs, and, as tumors are not independent
organs within an organism, this system is integrally involved in tumor growth and
progression.
PMID- 29334993
TI - Quality of life in mucopolysaccharidoses: construction of a specific measure
using the focus group technique.
AB - OBJECTIVE: To describe the perceptions of patients, their caregivers, and their
healthcare providers to the development of a new specific instrument for
assessment of the quality of life (QoL) in patients with mucopolysaccharidoses
(MPS) using a qualitative focus group (FG) design. FGs were held in two Brazilian
states (Rio Grande do Sul and Rio de Janeiro). RESULTS: Three versions of the new
instrument were developed, each for a different age group: children (age 8-12
years), adolescents (age 13-17), and adults (age >= 18). The FGs mostly confirmed
the relevance of items. All FGs unanimously agreed on the facets: School,
Happiness, Life Prospects, Religiosity, Pain, Continuity of Treatment, Trust in
Treatment, Relationship with Family, Relationship with Healthcare Providers,
Acceptance, and Meaning of Life. The overall concept of QoL (as proposed by the
WHO-World Health Organization) and its facets apply to this patient population.
However, other specific facets-particularly concerning clinical manifestations
and the reality of the disease-were suggested, confirming the need for the
development of a specific QoL instrument for MPS.
PMID- 29334994
TI - The relationship between home- and individual-level diet quality among African
American and Hispanic/Latino households with young children.
AB - BACKGROUND: The quality of most Americans' diets is far from optimal. Given that
many Americans consume a significant portion of calories in the home, intervening
in this setting could be beneficial. However, the relationship between the home
food environment and diet quality is not well understood. This study examined the
relationship between diet quality at the individual level with home-level diet
quality using an index that measures compliance with federal dietary guidance.
METHODS: This was a cross sectional study that enrolled 97 African American and
Hispanic/Latino low-income parent-child dyads. Diet quality at the individual
level was assessed through two 24-h dietary recalls collected for parents and
children, respectively. Diet quality at the home level was assessed with two home
food inventories conducted in participants' homes. Diet quality scores at the
home and individual levels were computed by applying the Healthy Eating Index
2010 (HEI-2010) to these data. Linear models adjusted for potential confounding
factors were used to examine the relationship between diet quality at the home
and individual levels. RESULTS: Total HEI-2010 scores from parents and children's
diets were positively associated with HEI-2010 scores based on home food
inventories (parent diet: beta: 0.36, 95% CI: 012-0.60; child diet: 0.38 95% CI:
013-0.62). Positive associations were also observed between individual level and
home level subcomponent HEI-2010 scores for total fruit (parent: 0.55 95% CI:
0.16-0.94; child: 0.49 95% CI: 0.03-0.94), whole fruit (parent only: 0.41 95% CI:
0.07-0.74), greens and beans (parent only: 0.39 95% CI: 0.05-0.74), and whole
grain (children only: 0.33 95% CI: 0.04-0.63). CONCLUSION: This study
demonstrated that individual level diet quality was positively associated with
home-level diet quality. Findings from this study can help us to address
modifiable targets of intervention in the home to improve diet quality.
PMID- 29334995
TI - Antisense suppression of the nonsense mediated decay factor Upf3b as a potential
treatment for diseases caused by nonsense mutations.
AB - BACKGROUND: About 11% of all human genetic diseases are caused by nonsense
mutations that generate premature translation termination codons (PTCs) in
messenger RNAs (mRNA). PTCs not only lead to the production of truncated
proteins, but also often result in decreased mRNA abundance due to nonsense
mediated mRNA decay (NMD). Although pharmacological inhibition of NMD could be an
attractive therapeutic approach for the treatment of diseases caused by nonsense
mutations, NMD also regulates the expression of 10-20% of the normal
transcriptome. RESULTS: Here, we investigate whether NMD can be inhibited to
stabilize mutant mRNAs, which may subsequently produce functional proteins,
without having a major impact on the normal transcriptome. We develop antisense
oligonucleotides (ASOs) to systematically deplete each component in the NMD
pathway. We find that ASO-mediated depletion of each NMD factor elicits different
magnitudes of NMD inhibition in vitro and are differentially tolerated in normal
mice. Among all of the NMD factors, Upf3b depletion is well tolerated, consistent
with previous reports that UPF3B is not essential for development and regulates
only a subset of the endogenous NMD substrates. While minimally impacting the
normal transcriptome, Upf3b-ASO treatment significantly stabilizes the PTC
containing dystrophin mRNA in mdx mice and coagulation factor IX mRNA in a
hemophilia mouse model. Furthermore, when combined with reagents promoting
translational read-through, Upf3b-ASO treatment leads to the production of
functional factor IX protein in hemophilia mice. CONCLUSIONS: These data
demonstrate that ASO-mediated reduction of the NMD factor Upf3b could be an
effective and safe approach for the treatment of diseases caused by nonsense
mutations.
PMID- 29334997
TI - Effects of three frequencies of self-monitored blood glucose on HbA1c and quality
of life in patients with type 2 diabetes with once daily insulin and stable
control: a randomized trial.
AB - OBJECTIVE: The optimal frequency of self-monitoring of blood glucose (SMBG) in
patients with type 2 diabetes (T2DM) with stable glycemic control is unknown.
This study investigated effects of 3 frequencies of SMBG on glycemic control and
quality of life after 9 months in patients using one long-acting insulin
injection a day. In an open-label, multi-center, primary-care, parallel (1:1:1)
randomized trial in the Netherlands including patients with T2DM, HbA1c <= 58
mmol/mol (<= 7.5%), stable glycemic control, treated with one insulin injection
daily, three frequencies of 4-point glucose measurements (before meals and
bedtime) were weekly (n = 22), every 2 weeks (n = 16) and monthly (n = 20) were
compared. RESULTS: A total of 58 patients with T2DM were included by 38 general
practitioners, which was lower then anticipated. There were no significant
between group differences in HbA1c (mmol/mol); group C compared to A and B; - 2.7
(95% CI - 6.4, 1.0) and - 1.0 (95% CI - 4.9, 3.0) and quality of life. Baring in
mind the lower than anticipated inclusion rate, there were no significant
differences in HbA1c and quality of life between three different frequencies of
SMBG in patients with stable glycemic control using one long-acting insulin
injection. Trial registration NCT01460459, registered 10-2011, recruitment
between 05-2011 and 12-2011.
PMID- 29334998
TI - Examining human paragonimiasis as a differential diagnosis to tuberculosis in The
Gambia.
AB - OBJECTIVE: Paragonimiasis is a foodborne trematode infection of the lungs caused
by Paragonimus spp., presenting clinically with similar symptoms to active
tuberculosis (TB). Worldwide, an estimated 20.7 million people are infected with
paragonimiasis, but relatively little epidemiological data exists for Africa.
Given a recently reported case, we sought to establish whether paragonimiasis
should be considered as an important differential diagnosis for human TB in The
Gambia, West Africa. RESULTS: We developed a novel PCR-based diagnostic test for
Paragonimus species known to be found in West Africa, which we used to examine
archived TB negative sputum samples from a cross-sectional study of volunteers
with tuberculosis-like symptoms from communities in the Western coastal region of
The Gambia. Based on a "zero patient" design for detection of rare diseases, 300
anonymised AFB smear negative sputum samples, randomly selected from 25 villages,
were screened for active paragonimiasis by molecular detection of Paragonimus
spp. DNA. No parasite DNA was found in any of the sputa of our patient group.
Despite the recent case report, we found no evidence of active paragonimiasis
infection masking as TB in the Western region of The Gambia.
PMID- 29334996
TI - Italian guidelines on the assessment and management of pediatric head injury in
the emergency department.
AB - OBJECTIVE: We aim to formulate evidence-based recommendations to assist
physicians decision-making in the assessment and management of children younger
than 16 years presenting to the emergency department (ED) following a blunt head
trauma with no suspicion of non-accidental injury. METHODS: These guidelines were
commissioned by the Italian Society of Pediatric Emergency Medicine and include a
systematic review and analysis of the literature published since 2005. Physicians
with expertise and experience in the fields of pediatrics, pediatric emergency
medicine, pediatric intensive care, neurosurgery and neuroradiology, as well as
an experienced pediatric nurse and a parent representative were the components of
the guidelines working group. Areas of direct interest included 1) initial
assessment and stabilization in the ED, 2) diagnosis of clinically important
traumatic brain injury in the ED, 3) management and disposition in the ED. The
guidelines do not provide specific guidance on the identification and management
of possible associated cervical spine injuries. Other exclusions are noted in the
full text. CONCLUSIONS: Recommendations to guide physicians practice when
assessing children presenting to the ED following blunt head trauma are reported
in both summary and extensive format in the guideline document.
PMID- 29334999
TI - The plant alkaloid tetrandrine inhibits metastasis via autophagy-dependent
Wnt/beta-catenin and metastatic tumor antigen 1 signaling in human liver cancer
cells.
AB - BACKGROUND: Tetrandrine is a bisbenzylisoquinoline alkaloid isolated from the
Chinese medicinal herb Stephania tetrandra S. Moore. We previously demonstrated
that tetrandrine exhibits potent antitumor effects in many types of cancer cells.
In this study, we investigated the effects of tetrandrine on human hepatocellular
carcinoma (HCC) metastasis. METHODS: The invasion and migration effects were
evaluated via wound healing and transwell assays. Immunofluorescence and western
blotting analyses were used to investigate the levels of epithelial-mesenchymal
transition (EMT)-related protein. A metastasis model was established to
investigate the inhibitory effect of tetrandrine on hepatocellular carcinoma
metastasis in vivo. RESULTS: Tetrandrine inhibits HCC invasion and migration by
preventing cell EMT. The underlying mechanism was closely associated with
tetrandrine-induced human liver cell autophagy, which inhibits Wnt/beta-catenin
pathway activity and decreases metastatic tumor antigen 1 (MTA1) expression to
modulate cancer cell metastasis. CONCLUSION: Our findings demonstrate, for the
first time, that tetrandrine plays a significant role in the inhibition of human
hepatocellular carcinoma metastasis and provide novel insights into the
application of tetrandrine in clinical HCC treatment.
PMID- 29335001
TI - Different clinical presentation and management of temporal bone fibrous dysplasia
in children.
AB - BACKGROUND: Fibrous dysplasia is a slowly progressive benign fibro-osseous
disorder that involves one or multiple bones with a unilateral distribution in
most cases. It is a lesion of unknown etiology, uncertain pathogenesis, and
diverse histopathology. Temporal bone involvement is the least frequently
reported type, especially in children. We reviewed available articles regarding
fibrous dysplasia with temporal bone involvement in children and added four
patients aged 7 to 17 years who were diagnosed and treated in our institution
from 2006 to 2017. The patients' clinical picture comprised head deformity,
external canal stenosis, headache, progressive conductive and/or sensorineural
hearing loss, tinnitus, and sudden deafness. Two patients had experienced severe
episodic vertigo with nausea and vomiting. Two were referred to us with external
canal obstruction and secondary cholesteatoma formation with broad middle ear
destruction. One was diagnosed with acute mastoiditis and intracranial
complications. Optimal management of fibrous dysplasia is unclear and can be
challenging, especially in children. In our two patients with disease expansion
and involvement of important structures, surgical treatment was abandoned and a
"wait-and-scan" policy was applied. The other two were qualified for surgical
treatment. One patient underwent two surgeries: modified lateral petrosectomy
(canal left open) with pathological tissue removal, cavity obliteration, and
subsequent tympanoplasty. Another patient with extensive destruction of the left
temporal bone underwent canal wall down mastoidectomy with perisinus abscess
drainage and revision 12 months later. Tympanoplasty was unsatisfactory in both
patients because of slow progression of the middle ear pathology. None of our
patients underwent pharmacological treatment. CONCLUSIONS: In younger patients,
observation and a "wait-and-scan" protocol is relevant until significant
function, or cosmetic deficits are obvious. Surgery is not preferred and should
be delayed until puberty because fibrous dysplasia has a tendency to stabilize
after adolescence. In patients with severe symptoms medical treatment can be
implemented, but safety of this treatment in children remain controversial.
PMID- 29335000
TI - Molecular characterization of Babesia microti thioredoxin (BmTrx2) and its
expression patterns induced by antiprotozoal drugs.
AB - BACKGROUND: Human babesiosis is an infectious disease that is epidemic in various
regions all over the world. The predominant causative pathogen of this disease is
the intra-erythrocytic parasite Babesia microti. The thioredoxin system is one of
the major weapons that is used in the resistance to the reactive oxygen species
(ROS) and reactive nitrogen species (RNS) produced by host immune system. In
other intra-erythrocytic apicomplexans like the malaria parasite Plasmodium
falciparum, anti-oxidative proteins are promising targets for the development of
anti-parasitic drugs. However, to date, the sequences and biological properties
of thioredoxins and thioredoxin-like molecules of B. microti remain unknown.
Understanding the molecular characterization and function of B. microti
thioredoxins may help to develop anti-Babesia drugs and controlling babesiosis.
METHODS: The full-length B. microti thioredoxin 2 (BmTrx2) gene was obtained
using a rapid amplification of cDNA ends (RACE) method, and the deduced BmTrx2
amino acid sequence was analyzed using regular bioinformatics tools. Recombinant
BmTrx2 protein was expressed in vitro and purified using His-tag protein affinity
chromatography resins. Reverse transcription PCR, quantitative real-time PCR and
Western blot were employed to detect the expression and native proteins of
BmTrx2. Indirect immunofluorescence assay was used to localize BmTrx2 in B.
microti. Bovine insulin reduction assays were used to determine the enzyme
activity of the purified recombinant BmTrx2 protein. RESULTS: The full-length
BmTrx2 was 564 bp with a 408 bp open reading frame encoding a protein of 135
amino acids. The predicted molecular weight of the protein was 15.5 kDa. A
conserved thioredoxin-like family domain was found in BmTrx2. The expression of
BmTrx2 was upregulated on both the third and eighth day post-infection in mice,
whereas expression was downregulated during the beginning and later stages. The
results of Western blot analysis showed the native BmTrx2 in parasite lysates
could be detected by mouse anti-BmTrx2 serum and that the recombinant BmTrx2
protein could be recognized by serum of B. microti-infected mice.
Immunofluorescence microscopy showed that BmTrx2 localized in the cell cytoplasm
of B. microti merozoites in B. microti-infected red blood cells. The results of
bovine insulin reduction assay indicated the purified recombinant BmTrx2 protein
possesses antioxidant enzyme activity. Dihydroartemisinin and quinine, known anti
malaria drugs, and clindamycin, a known anti-babesiosis drug, induced
significantly higher upregulation of BmTrx2 mRNA. CONCLUSIONS: Our results
indicate that BmTrx2 is a functional enzyme with antioxidant activity and may be
involved in the response of B. microti to anti-parasite drugs.
PMID- 29335002
TI - Leishmania mortality in sand fly blood meal is not species-specific and does not
result from direct effect of proteinases.
AB - BACKGROUND: Leishmania development in sand flies is confined to the alimentary
tract and is closely connected with blood meal digestion. Previously, it has been
published that activities of sand fly midgut proteases are harmful to Leishmania,
especially to amastigote-promastigote transition forms. However, our experiments
with various Leishmania-sand fly pairs gave quite opposite results. METHODS: We
evaluated the effect of semi-digested midgut content on different life stages of
Leishmania donovani and Leishmania major in vitro. Various morphological forms of
parasites, including macrophage-derived amastigotes and transition forms, were
incubated 2 h with midguts dissected at various intervals (6-72 h) post-blood
meal or with commercially available proteinase, and their viability was
determined using flow cytometry. In parallel, using amastigote-initiated
experimental infections, we compared development of L. donovani in sand flies
that are either susceptible (Phlebotomus argentipes and P. orientalis) or
refractory (P. papatasi and Sergentomyia schwetzi) to this parasite. RESULTS: In
vitro, sand fly midgut homogenates affected L. major and L. donovani in a similar
way; in all sand fly species, the most significant mortality effect was observed
by the end of the blood meal digestion process. Surprisingly, the most
susceptible Leishmania stages were promastigotes, while mortality of transforming
parasites and amastigotes was significantly lower. Parasites were also
susceptible to killing by rabbit blood in combination with proteinase, but
resistant to proteinase itself. In vivo, L. donovani developed late-stage
infections in both natural vectors; in P. argentipes the development was much
faster than in P. orientalis. On the other hand, in refractory species P.
papatasi and S. schwetzi, promastigotes survived activity of digestive enzymes
but were lost during defecation. CONCLUSIONS: We demonstrated that Leishmania
transition forms are more resistant to the killing effect of semi-digested blood
meal than 24 h-old promastigotes. Data suggest that Leishmania mortality is not
caused directly by sand fly proteases, we assume that this mortality results from
toxic products of blood meal digestion. Survival of L. donovani promastigotes in
refractory sand flies until blood meal defecation, together with similar
mortality of Leishmania parasites incubated in vitro with midgut homogenates of
susceptible as well as refractory species, contradict the previously raised
hypotheses about the role of midgut proteases in sand fly vector competence to
Leishmania.
PMID- 29335003
TI - Antihypertensive medication adherence and associated factors among adult
hypertensive patients at Jimma University Specialized Hospital, southwest
Ethiopia.
AB - BACKGROUND: Adherence to antihypertensive medications is a key component to
control blood pressure levels. Poor adherence to these medications leads to the
development of hypertensive complications and increase risk of cardiovascular
events which in turn reduces the ultimate clinical outcome. The purpose of this
study was to assess antihypertensive medication adherence and associated factors
among adult hypertensive patients. A hospital-based cross-sectional study among
adult hypertensive patients was conducted at hypertensive follow-up clinic of
Jimma University Specialized Hospital from March 4, 2015 to April 3, 2015. A
simple random sampling technique was used to select the study participants from
the study population. The study patients were interviewed and their medical
charts were reviewed using a pretested structured questionnaire. Adherence was
assessed using Morisky Medication Adherence Scale-8 (MMAS-8) and MMAS-8 score
less than 6 was considered as non-adherent and MMAS-8 score was >= 6 was declared
as adherence. Factors associated with adherence were identified using binary and
multivariate logistic regression analysis. Crude odds ratio, adjusted odds ratio
(AOR) and 95% confidence interval of the odds ratio were calculated using SPSS
version 21. Variables with p-value less than 0.05 were assumed as statistically
significant factors. RESULTS: Among 280 hypertensive patients, 61.8% of the study
participants were found to be adherent. More than half (53.2%) of the
participants were males and the mean age of the participants was 55.0 +/- 12.7
years. Co-morbidity (AOR = 0.083, 95% CI = 0.033-0.207, p < 0.001), alcohol
intake (AOR = 0.011, 95% CI = 0.002-0.079, p < 0.001), getting medications freely
(AOR = 0.020, 95% CI = 0.003-0.117, p < 0.001), and combination of
antihypertensive medications (AOR = 0.32, 95% CI = 0.144-0.712, p < 0.005) were
inversely associated with antihypertensive medication adherence. CONCLUSION: The
adherence level to the prescribed antihypertensive medications was found to be
sub-optimal according to the MMAS-8, and influenced by co morbidity, alcohol
intake, self-purchasing of the medications and combination of antihypertensive
medications.
PMID- 29335004
TI - Factors associated with poor treatment outcome of tuberculosis in Debre Tabor,
northwest Ethiopia.
AB - OBJECTIVE: Directly observed treatment short course has been implemented as part
of the national tuberculosis control program in Ethiopia. The strategy, as
evidenced by different studies, has improved the survival and treatment success
rate of tuberculosis patients. However, some patients failed to complete their
treatments and the factors for this failure were not assessed in the study area.
We, therefore sought to identify factors associated with poor treatment outcome
of tuberculosis in Debre Tabor, northwest Ethiopia. RESULTS: We included 303
patients (173 males, 130 females) with mean age of 34.9 years in the study and 39
(12.9%) patients were with poor treatment outcome over the period of 5 years
(2008-2013). Being male, urban residency, positive and unknown smear result at
the 2nd month of treatment and patients in the age of 35-44 years were more
likely to have poor treatment outcomes than their counterparts. Patients in the
new treatment category were less likely to have poor treatment outcome compared
to the retreated cases. Further studies are recommended to explore the
association of poor treatment outcome with other important factors which are not
investigated by this study.
PMID- 29335005
TI - In-depth resistome analysis by targeted metagenomics.
AB - BACKGROUND: Antimicrobial resistance is a major global health challenge.
Metagenomics allows analyzing the presence and dynamics of "resistomes" (the
ensemble of genes encoding antimicrobial resistance in a given microbiome) in
disparate microbial ecosystems. However, the low sensitivity and specificity of
available metagenomic methods preclude the detection of minority populations
(often present below their detection threshold) and/or the identification of
allelic variants that differ in the resulting phenotype. Here, we describe a
novel strategy that combines targeted metagenomics using last generation in
solution capture platforms, with novel bioinformatics tools to establish a
standardized framework that allows both quantitative and qualitative analyses of
resistomes. METHODS: We developed ResCap, a targeted sequence capture platform
based on SeqCapEZ (NimbleGene) technology, which includes probes for 8667
canonical resistance genes (7963 antibiotic resistance genes and 704 genes
conferring resistance to metals or biocides), and 2517 relaxase genes (plasmid
markers) and 78,600 genes homologous to the previous identified targets (47,806
for antibiotics and 30,794 for biocides or metals). Its performance was compared
with metagenomic shotgun sequencing (MSS) for 17 fecal samples (9 humans, 8
swine). ResCap significantly improves MSS to detect "gene abundance" (from 2.0 to
83.2%) and "gene diversity" (26 versus 14.9 genes unequivocally detected per
sample per million of reads; the number of reads unequivocally mapped increasing
up to 300-fold by using ResCap), which were calculated using novel bioinformatic
tools. ResCap also facilitated the analysis of novel genes potentially involved
in the resistance to antibiotics, metals, biocides, or any combination thereof.
CONCLUSIONS: ResCap, the first targeted sequence capture, specifically developed
to analyze resistomes, greatly enhances the sensitivity and specificity of
available metagenomic methods and offers the possibility to analyze genes related
to the selection and transfer of antimicrobial resistance (biocides, heavy
metals, plasmids). The model opens the possibility to study other complex
microbial systems in which minority populations play a relevant role.
PMID- 29335007
TI - Stress-inducible Protein-1 promotes metastasis of gastric cancer via Wnt/beta
catenin signaling pathway.
AB - BACKGROUND: Stress-Inducible Protein-1 (STIP1) is a co-chaperone that associates
directly with heat shock proteins, and regulates motility of various types of
cancer. In the present study, we investigated the role of STIP1 on metastasis of
gastric cancer (GC). METHODS: In vivo metastatic experimental model was employed
to investigate the effect of STIP1 on metastasis of GC cells. Loss-of-function
and gain-of-function experiments were performed to examine the role of STIP1 on
metastasis of GC cells. Western blot, immunofluorescence staining, migration and
invasion assays, microarray and KEGG pathway analysis were applied to explore the
underlying mechanism. RESULTS: In current study, we demonstrated that STIP1
promoted lung metastasis of GC cells in vivo. Furthermore, STIP1 significantly
enhanced migration and invasion abilities of GC cells. In contrast, knock-down of
STIP1 yielded the opposite effects on these phenotypes in vitro. STIP1 promoted
tumor metastasis through inducing epithelial-to-mesenchymal transition in GC
cells. Mechanistically, STIP1 promoted GC metastasis via up-regulation of
targeted genes in Wnt/beta-catenin signaling pathway, including c-Myc and Cyclin
D1, and accompanied with nuclear translocation of beta-catenin. CONCLUSIONS: Our
findings indicate that elevated expression of STIP1 exhibited a metastasis
promoting effect in GC cells through activation of Wnt/beta-catenin signaling
pathway. STIP1 may be served as a potential therapeutic target for preventing GC
metastasis.
PMID- 29335006
TI - Genetic dissection of the neuro-glio-vascular machinery in the adult brain.
AB - The adult brain actively controls its metabolic homeostasis via the circulatory
system at the blood brain barrier interface. The mechanisms underlying the
functional coupling from neuron to vessel remain poorly understood. Here, we
established a novel method to genetically isolate the individual components of
this coupling machinery using a combination of viral vectors. We first discovered
a surprising non-uniformity of the glio-vascular structure in different brain
regions. We carried out a viral injection screen and found that intravenous
Canine Adenovirus 2 (CAV2) preferentially targeted perivascular astrocytes
throughout the adult brain, with sparing of the hippocampal hilus from infection.
Using this new intravenous method to target astrocytes, we selectively ablated
these cells and observed severe defects in hippocampus-dependent contextual
memory and the metabolically regulated process of hippocampal neurogenesis.
Combined with AAV9 targeting of neurons and endothelial cells, all components of
the neuro-glio-vascular machinery can be simultaneously labeled for genetic
manipulation. Together, we demonstrate a novel method, which we term CATNAP
(CAV/AAV Targeting of Neurons and Astrocytes Perivascularly), to target and
manipulate the neuro-glio-vascular machinery in the adult brain.
PMID- 29335009
TI - Isolated follicle stimulated hormone deficiency in male: case report.
AB - BACKGROUND: Recent rapid advances in assisted reproductive health technologies
enables couples with subfertility to conceive through various intervention.
Majority of treatment modalities target the female partner. However it is
important to identify and treat male factor subfertility right at the outset. We
report a case of isolated follicle stimulating hormone deficiency resulting in
azoospermia and primary subfertility. CASE PRESENTATION: A 28 year otherwise
healthy male presented with primary subfertility with a healthy female
counterpart. He was found to have non obstructive azoospermia with low seminal
fluid volume. He had normal external genitalia and potency with increased libido.
Further evaluation revealed an isolated deficiency of follicle stimulating
hormone with elevated testosterone levels. His luteinizing hormone and prolactin
levels were normal. Contrast enhanced CT scan of chest, abdomen and pelvis and
MRI scan of the pituitary fossa were normal too. CONCLUSION: In the era of modern
reproductive technology it is important to further evaluate males with non
obstructive azoospermia to detect underlying gonadotropin deficiency.
PMID- 29335008
TI - Multi-omics differentially classify disease state and treatment outcome in
pediatric Crohn's disease.
AB - BACKGROUND: Crohn's disease (CD) has an unclear etiology, but there is growing
evidence of a direct link with a dysbiotic microbiome. Many gut microbes have
previously been associated with CD, but these have mainly been confounded with
patients' ongoing treatments. Additionally, most analyses of CD patients'
microbiomes have focused on microbes in stool samples, which yield different
insights than profiling biopsy samples. RESULTS: We sequenced the 16S rRNA gene
(16S) and carried out shotgun metagenomics (MGS) from the intestinal biopsies of
20 treatment-naive CD and 20 control pediatric patients. We identified the
abundances of microbial taxa and inferred functional categories within each
dataset. We also identified known human genetic variants from the MGS data. We
then used a machine learning approach to determine the classification accuracy
when these datasets, collapsed to different hierarchical groupings, were used
independently to classify patients by disease state and by CD patients' response
to treatment. We found that 16S-identified microbes could classify patients with
higher accuracy in both cases. Based on follow-ups with these patients, we
identified which microbes and functions were best for predicting disease state
and response to treatment, including several previously identified markers. By
combining the top features from all significant models into a single model, we
could compare the relative importance of these predictive features. We found that
16S-identified microbes are the best predictors of CD state whereas MGS
identified markers perform best for classifying treatment response. CONCLUSIONS:
We demonstrate for the first time that useful predictors of CD treatment response
can be produced from shotgun MGS sequencing of biopsy samples despite the
complications related to large proportions of host DNA. The top predictive
features that we identified in this study could be useful for building an
improved classifier for CD and treatment response based on sufferers' microbiome
in the future. The BISCUIT project is funded by a Clinical Academic Fellowship
from the Chief Scientist Office (Scotland)-CAF/08/01.
PMID- 29335010
TI - Acute intestinal obstruction due to extrinsic compression by previa myoma and
ectopic pregnancy: a case report.
AB - BACKGROUND: Acute intestinal obstruction during pregnancy is a rare digestive
surgical emergency with significant maternal and fetal mortality. Diagnosis is
difficult, often delaying the management. Here, we report an exceptional
association of mechanical acute intestinal obstruction due to compression by
previa uterine leiomyoma, and a ruptured ectopic pregnancy. CASE PRESENTATION:
This is the case report of a 43-year-old primiparous black woman from a rural
area, who was admitted to the surgical emergency department for acute intestinal
obstruction. At examination on admittance, our patient had a bad general
condition with clinical anemia. She had an occlusive syndrome that had been
evolving for 3 days. A physical examination of her abdomen showed a widespread
distension with an irregular and polylobed solid mass occupying the whole of the
lower-umbilical and hypogastric area. A rectal examination found an empty rectum,
and the mass was perceptible in Douglas's pouch. At the vaginal examination, we
found the same mass and a finger holster was clean. The diagnosis of intestinal
occlusion by a tumor was retained. The laparotomy revealed a distended intestine,
a ruptured right tubal ectopic pregnancy and a polymyomatous uterus. The most
massive previa leiomyoma was adhering and compressing the rectal and sigmoidal
hinge. A total hysterectomy was performed and histopathological examination of
specimens confirmed myoma and ectopic pregnancy. The surgical follow-up was
uneventful, and our patient was discharged on postoperative day 12. CONCLUSIONS:
The etiological diagnosis of acute intestinal obstruction during pregnancy is not
easy, especially in the context of a low-income country where the means of
biological and radiological diagnosis are lacking. A laparotomy is required
before diagnosis of acute surgical abdomen and its management will depend on the
intraoperative findings and the condition of the patient.
PMID- 29335011
TI - Generalized estimation of the ventilatory distribution from the multiple-breath
washout: a bench evaluation study.
AB - BACKGROUND: The multiple-breath washout (MBW) is able to provide information
about the distribution of ventilation-to-volume (v/V) ratios in the lungs.
However, the classical, all-parallel model may return skewed results due to the
mixing effect of a common dead space. The aim of this work is to examine whether
a novel mathematical model and algorithm is able to estimate v/V of a physical
model, and to compare its results with those of the classical model. The novel
model takes into account a dead space in series with the parallel ventilated
compartments, allows for variable tidal volume (VT) and end-expiratory lung
volume (EELV), and does not require a ideal step change of the inert gas
concentration. METHODS: Two physical models with preset v/V units and a common
series dead space (vd) were built and mechanically ventilated. The models
underwent MBW with N2 as inert gas, throughout which flow and N2 concentration
signals were acquired. Distribution of v/V was estimated-via nonnegative least
squares, with Tikhonov regularization-with the classical, all-parallel model
(with and without correction for non-ideal inspiratory N2 step) and with the new,
generalized model including breath-by-breath vd estimates given by the Fowler
method (with and without constrained VT and EELV). RESULTS: The v/V distributions
estimated with constrained EELV and VT by the generalized model were practically
coincident with the actual v/V distribution for both physical models. The v/V
distributions calculated with the classical model were shifted leftwards and
broader as compared to the reference. CONCLUSIONS: The proposed model and
algorithm provided better estimates of v/V than the classical model, particularly
with constrained VT and EELV.
PMID- 29335012
TI - The polycomb group protein EZH2 induces epithelial-mesenchymal transition and
pluripotent phenotype of gastric cancer cells by binding to PTEN promoter.
AB - BACKGROUND: The influences of oncogenic Ezh2 on the progression and prognosis of
gastric cancer (GC) and the underlying mechanisms are still poorly understood.
Here, we aimed at investigating clinicopathological significance of Ezh2 in GC
and the mechanisms underlying its function in GC development. METHODS: The
expression level of Ezh2 was determined by qRT-PCR, immunoblot, and
immunohistochemistry analysis in 156 pairs of GC tissues and adjacent normal
gastric mucosa tissues. The biological functions of Ezh2 were assessed by in
vitro and in vivo functional experiments. Chromatin immunoprecipitation (ChIP),
luciferase, and Western blotting analyses were utilized to identify the
relationship between Ezh2 and the PTEN/Akt signaling. RESULTS: The expression of
Ezh2 was higher in gastric cancer tissues in comparison with para-nontumorous
epithelium. High expression of Ezh2 was associated with more aggressive
biological behavior and poor prognosis in GC. In vitro studies indicated that
Ezh2 promoted GC cells' proliferation and clonogenicity. Besides, Ezh2 led to the
acquisition of epithelial-mesenchymal transition (EMT) phenotype of GC cells and
enhanced GC cell migration and invasion capacity. In particular, Ezh2
strengthened sphere-forming capacity of GC cells, indicating its role in the
enrichment of GC stem cells. Furthermore, we found that PTEN/Akt signaling
contributed to the effects of Ezh2 on cancer stem cells (CSC) and EMT phenotype
in GC cells, and blocking PTEN signaling significantly rescued the effects of
Ezh2. CONCLUSIONS: Taken together, Ezh2 has a central role in regulating diverse
aspects of the pathogenesis of GC in part by involving PTEN/Akt signaling,
indicating that it could be an independent prognostic factor and potential
therapeutic target.
PMID- 29335013
TI - FIT for FUNCTION: study protocol for a randomized controlled trial.
AB - BACKGROUND: The current state of evidence suggests that community-based exercise
programs are beneficial in improving impairment, function, and health status, and
are greatly needed for persons with stroke. However, limitations of these studies
include risk of bias, feasibility, and cost issues. METHODS/DESIGN: This single
blinded, randomized controlled trial (RCT) of 216 participants with stroke will
compare the effectiveness of a 12-week YMCA community-based wellness program (FIT
for FUNCTION) specifically designed for community-dwelling persons with stroke to
persons who receive a standard YMCA membership. The primary outcome will be
community reintegration using the Reintegration to Normal Living Index at 12 and
24 weeks. Secondary outcomes include measurement of physical activity level using
the Rapid Assessment of Physical Activity and accelerometry; balance using the
Berg Balance Scale; lower extremity function using the Short Physical Performance
Battery; exercise capacity using the 6-min walk test; grip strength and isometric
knee extension strength using hand held dynamometry; and health-related quality
of life using the European Quality of Life 5-Dimension Questionnaire. We are also
assessing cardiovascular health and lipids; glucose and inflammatory markers will
be collected following 12-h fast for total cholesterol, insulin, glucose, and
glycated hemoglobin. Self-efficacy for physical activity will be assessed with a
single question and self-efficacy for managing chronic disease will be assessed
using the Stanford 6-item Scale. The Patient Activation Measure will be used to
assess the patient's level of knowledge, skill, and confidence for self
management. Healthcare utilization and costs will be evaluated. Group, time, and
group * time interaction effects will be estimated using generalized linear
models for continuous variables, including relevant baseline variables as
covariates in the analysis that differ appreciably between groups at baseline.
Cost data will be treated as non-parametric and analyzed using a Mann-Whitney U
test. DISCUSSION: This is a RCT with broad study eligibility criteria intended to
recruit a wide spectrum of individuals living in the community with stroke. If
positive benefits are demonstrated, results will provide strong research evidence
to support the implementation of structured, community-based exercise and
education/self-management programs for a broad range of people living in the
community with stroke. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02703805 .
Registered on 14 October 2014.
PMID- 29335014
TI - Cost-effectiveness study of early versus late parenteral nutrition in critically
ill children (PEPaNIC): preplanned secondary analysis of a multicentre randomised
controlled trial.
AB - BACKGROUND: The multicentre randomised controlled PEPaNIC trial showed that
withholding parenteral nutrition (PN) during the first week of critical illness
in children was clinically superior to providing early PN. This study describes
the cost-effectiveness of this new nutritional strategy. METHODS: Direct medical
costs were calculated with use of a micro-costing approach. We compared the costs
of late versus early initiation of PN (n = 673 versus n = 670 patients) in the
Belgian and Dutch study populations from a hospital perspective, using Student's
t test with bootstrapping. Main cost drivers were identified and the impact of
new infections on the total costs was assessed. RESULTS: Mean direct medical
costs for patients receiving late PN (?26.680, IQR ?10.090-28.830 per patient)
were 21% lower (-?7.180, p = 0.007) than for patients receiving early PN
(?33.860, IQR ?11.080-34.720). Since late PN was more effective and less costly,
this strategy was superior to early PN. The lower costs for PN only contributed
2.1% to the total cost reduction. The main cost driver was intensive care
hospitalisation costs (-?4.120, p = 0.003). The patients who acquired a new
infection (14%) were responsible for 41% of the total costs. Sensitivity analyses
confirmed consistency across both healthcare systems. CONCLUSIONS: Late
initiation of PN decreased the direct medical costs for hospitalisation in
critically ill children, beyond the expected lower costs for withholding PN.
Avoiding new infections by late initiation of PN yielded a large cost reduction.
Hence, late initiation of PN was superior to early initiation of PN largely via
its effect on new infections. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01536275
. Registered on 16 February 2012.
PMID- 29335015
TI - Cryptic diversity in an Atlantic Forest malaria vector from the mountains of
South-East Brazil.
AB - BACKGROUND: Anopheles (Kerteszia) cruzii is the primary vector of human and
simian malarias in Brazilian regions covered by the Atlantic Rainforest. Previous
studies found that An. cruzii presents high levels of behavioural, chromosomal
and molecular polymorphisms, which led to the hypothesis that it may be a complex
of cryptic species. Here, An. cruzii specimens were collected in five sites in
South-East Brazil located at different altitudes on the inner and coastal slopes
of two mountain ranges covered by Atlantic Rainforest, known as Serra do Mar and
Serra da Mantiqueria. Partial sequences for two genes (Clock and cpr) were
generated and compared with previously published sequences from Florianopolis
(southern Brazil). Genetic diversity was analysed with estimates of population
structure (F ST ) and haplotype phylogenetic trees in order to understand how
many species of the complex may occur in this biome and how populations across
the species distribution are related. RESULTS: The sequences from specimens
collected at sites located on the lower coastal slopes of Serra do Mar
(Guapimirim, Tingua and Sana) clustered together in the phylogenetic analysis,
while the major haplotypes from sites located on higher altitude and at the
continental side of the same mountains (Bocaina) clustered with those from Serra
da Mantiqueira (Itatiaia), an inner mountain range. These two An. cruzii lineages
showed statistically significant genetic differentiation and fixed characters,
and have high F ST values typical of between species comparisons. Finally, in
Bocaina, where the two lineages occur in sympatry, we found deviations from Hardy
Weinberg equilibrium due to a deficit of heterozygotes, indicating partial
reproductive isolation. These results strongly suggest that at least two distinct
lineages of An. cruzii (provisorily named "Group 1" and "Group 2") occur in the
mountains of South-East Brazil. CONCLUSIONS: At least two genetically distinct
An. cruzii lineages occur in the Atlantic Forest covered mountains of South-East
Brazil. The co-occurrence of distinct lineages of An. cruzii (possibly incipient
species) in those mountains is an interesting biological phenomenon and may have
important implications for malaria prevalence, Plasmodium transmission dynamics
and control.
PMID- 29335016
TI - Autophagy is required for human umbilical cord mesenchymal stem cells to improve
spatial working memory in APP/PS1 transgenic mouse model.
AB - BACKGROUND: Recent studies have shown that autophagy plays a central role in
mesenchymal stem cells (MSCs), and many studies have shown that human umbilical
cord MSCs (huMSCs) can treat Alzheimer's disease (AD) through a variety of
mechanisms. However, no studies have looked at the effects of autophagy on
neuroprotective function of huMSCs in the AD mouse model. Thus, in this study we
investigated whether inhibition of autophagy could weaken or block the function
of huMSCs through in vitro and in vivo experiments. METHODS: In vitro we examined
huMSC migration and neuronal differentiation by inhibiting or activating
autophagy; in vivo autophagy of huMSCs was inhibited by knocking down Beclin 1,
and these huMSCs were transplanted into the APP/PS1 transgenic mouse. A series of
related indicators were detected by T-maze task, electrophysiological
experiments, immunofluorescence staining, enzyme-linked immunosorbent assay
(ELISA), and Western blotting. RESULTS: We demonstrated that regulation of
autophagy can affect huMSC migration and their neuronal differentiation.
Moreover, inhibition of autophagy in huMSCs could not realize neuroprotective
effects via anti-apoptosis or promoting neurogenesis and synapse formation
compared with those of control huMSCs. CONCLUSIONS: These findings indicate that
autophagy is required for huMSCs to maintain their function and improve cognition
impairment in APP/PS1 transgenic mice.
PMID- 29335017
TI - Effect of laparoscopy by single-port endoscopic access in benign adnexal surgery:
study protocol for a randomized controlled trial.
AB - BACKGROUND: Laparoscopic surgery has become the preferred surgical approach due
to a reduction in postoperative pain, better recovery, shorter hospitalization,
and improved esthetic outcomes. Laparoscopic surgery with single-port laparoscopy
(SPL) is a laparoscopic surgery technique that is based on making a single
parietal incision using a single trocar specifically designed to allow
introduction of several instruments. The level of evidence regarding the
advantages of SPL in terms of postoperative pain has remained low despite several
randomized studies. Adult patients exhibiting a surgical indication for an a
priori benign ovarian pathology or for prophylactic purposes that can be
performed by laparoscopy will be randomized to receive conventional laparoscopy
(CL) or SPL. The aim of our study is to evaluate whether SPL offers advantages
over CL in benign adnexal surgery. METHODS: The patients will be evaluated
preoperatively to confirm their eligibility. The perioperative data up to 24 h
after the intervention, as well as the postoperative data at day 7 and at one
month from the intervention will be collected. The primary outcome for the study
will be the postoperative pain at 24 h +/- 2 h after the intervention. The pain
will be assessed by a numeric rating scale of 0-10. Other outcomes will also be
assessed, such as pain at other times, the consumption of analgesics, the
operative time, perioperative bleeding, the number of additional trocars in the
two groups, the incidence of laparoconversion, the esthetic criteria of the scar
at one month, the incidence of complications, and the quality of life at one
month. DISCUSSION: If our hypothesis is confirmed, this study will provide
evidence that the use of SPL can decrease postoperative pain in adnexal surgery.
The standard surgical treatment of this condition would thus be modified. TRIAL
REGISTRATION: ClinicalTrials.gov, NCT02739724 . Registered on 12 April 2016.
PMID- 29335018
TI - Danggwijagyaksan for climacteric syndrome in peri- and postmenopausal women with
a blood-deficiency dominant pattern: study protocol for a randomized, double
blind, placebo-controlled pilot trial.
AB - BACKGROUND: This study aims to explore the safety, efficacy, and feasibility of
Danggwijagyaksan (DJS) for alleviating climacteric syndrome in peri- and
postmenopausal women with a blood-deficiency dominant pattern. METHODS/DESIGN:
This is a randomized, double-blind, placebo-controlled pilot clinical trial. A
total of 34 women with climacteric syndrome who have signed informed consent
forms will be registered in this study. Placebo or DJS will be randomly assigned
to the participants in an equal proportion. The participants will visit the
clinical trial center every 2 weeks and receive placebo or DJS granules. The
treatment period is 4 weeks and the administration frequency is three times
daily. Data will be collected from the participants at baseline, at week 5, and
at week 9 after random allocation. The primary outcome measure will be the mean
change in the Menopause Rating Scale from baseline to week 5. Secondary outcome
measures will include the World Health Organization Quality of Life-BREF (WHOQOL
BREF) score, the Blood Deficiency Scoring System score, lean body mass, and blood
tests, including serum follicle-stimulating hormone and estradiol concentration.
To assess the safety of DJS, a laboratory test will be conducted before and after
treatment and the participants will be asked about any occurrence of adverse
events every visit. The recruitment rate, completion rate, and medication
adherence will also be calculated, to assess feasibility. DISCUSSION: The
findings of this study will provide the basis for a full-scale randomized
controlled trial to confirm the safety and efficacy of DJS for the treatment of
climacteric syndrome in peri- and postmenopausal women. TRIAL REGISTRATION:
Clinical Research Information Service (CRIS), Republic of Korea, KCT0002387 .
Registered on 25 July 2017.
PMID- 29335019
TI - Patient blood management programs: how to spread the word?
AB - Red blood cell (RBC) transfusions save lives and improve health; however,
unnecessary transfusion practice exposes patients to immediate and long-term
negative consequences. Indirect consequences of unnecessary transfusions are the
reduced availability of RBC units for patients who are in need. Accumulating
evidence shows that restricting RBC transfusions improves outcomes and current
guidelines suggest limiting RBC transfusion to the minimum number of units
required to relieve symptoms of anemia or to return the patient to a safe
hemoglobin range (7-8 g/dl in stable, non-cardiac inpatients). Still, studies
show that there is over-utilization of RBC transfusion, partly due to low level
of knowledge of physicians regarding restrictive RBC transfusion policy across a
broad range of professions and specialties. Patient blood management (PBM)
programs have been developed to promote clear hospital transfusion guidelines,
strive for optimization of patient hemoglobin and iron stores and, most
importantly, improve education regarding restrictive RBC policy. Understanding
what and where the gaps of knowledge are, as was done in the study by Dr. Koren
and his colleagues, is an important step for developing effective PBM programs.
PMID- 29335020
TI - Ensemble genomic analysis in human lung tissue identifies novel genes for chronic
obstructive pulmonary disease.
AB - BACKGROUND: Genome-wide association studies (GWAS) have identified single
nucleotide polymorphisms (SNPs) significantly associated with chronic obstructive
pulmonary disease (COPD). However, many genetic variants show suggestive evidence
for association but do not meet the strict threshold for genome-wide
significance. Integrative analysis of multiple omics datasets has the potential
to identify novel genes involved in disease pathogenesis by leveraging these
variants in a functional, regulatory context. RESULTS: We performed expression
quantitative trait locus (eQTL) analysis using genome-wide SNP genotyping and
gene expression profiling of lung tissue samples from 86 COPD cases and 31
controls, testing for SNPs associated with gene expression levels. These results
were integrated with a prior COPD GWAS using an ensemble statistical and network
methods approach to identify relevant genes and observe them in the context of
overall genetic control of gene expression to highlight co-regulated genes and
disease pathways. We identified 250,312 unique SNPs and 4997 genes in the
cis(local)-eQTL analysis (5% false discovery rate). The top gene from the
integrative analysis was MAPT, a gene recently identified in an independent GWAS
of lung function. The genes HNRNPAB and PCBP2 with RNA binding activity and the
gene ACVR1B were identified in network communities with validated disease
relevance. CONCLUSIONS: The integration of lung tissue gene expression with
genome-wide SNP genotyping and subsequent intersection with prior GWAS and omics
studies highlighted candidate genes within COPD loci and in communities harboring
known COPD genes. This integration also identified novel disease genes in sub
threshold regions that would otherwise have been missed through GWAS.
PMID- 29335022
TI - Tackling the challenges of matching biomedical ontologies.
AB - BACKGROUND: Biomedical ontologies pose several challenges to ontology matching
due both to the complexity of the biomedical domain and to the characteristics of
the ontologies themselves. The biomedical tracks in the Ontology Matching
Evaluation Initiative (OAEI) have spurred the development of matching systems
able to tackle these challenges, and benchmarked their general performance. In
this study, we dissect the strategies employed by matching systems to tackle the
challenges of matching biomedical ontologies and gauge the impact of the
challenges themselves on matching performance, using the AgreementMakerLight
(AML) system as the platform for this study. RESULTS: We demonstrate that the
linear complexity of the hash-based searching strategy implemented by most state
of-the-art ontology matching systems is essential for matching large biomedical
ontologies efficiently. We show that accounting for all lexical annotations
(e.g., labels and synonyms) in biomedical ontologies leads to a substantial
improvement in F-measure over using only the primary name, and that accounting
for the reliability of different types of annotations generally also leads to a
marked improvement. Finally, we show that cross-references are a reliable source
of information and that, when using biomedical ontologies as background
knowledge, it is generally more reliable to use them as mediators than to perform
lexical expansion. CONCLUSIONS: We anticipate that translating traditional
matching algorithms to the hash-based searching paradigm will be a critical
direction for the future development of the field. Improving the evaluation
carried out in the biomedical tracks of the OAEI will also be important, as
without proper reference alignments there is only so much that can be ascertained
about matching systems or strategies. Nevertheless, it is clear that, to tackle
the various challenges posed by biomedical ontologies, ontology matching systems
must be able to efficiently combine multiple strategies into a mature matching
approach.
PMID- 29335021
TI - Seroprevalence of dengue among healthy adults in a rural community in Southern
Malaysia: a pilot study.
AB - BACKGROUND: The frequency and magnitude of dengue epidemics continue to increase
exponentially in Malaysia, with a shift in the age range predominance toward
adults and an expansion to rural areas. Despite this, information pertaining to
the extent of transmission of dengue virus (DENV) in the rural community is
lacking. This community-based pilot study was conducted to establish DENV
seroprevalence amongst healthy adults in a rural district in Southern Malaysia,
and to identify influencing factors. METHODS: In this study undertaken between
April and May 2015, a total of 277 adult participants were recruited from
households across three localities in the Sungai Segamat subdistrict in Segamat
district. Sera were tested for immunoglobulin G (IgG) (Panbio(r) Dengue Indirect
IgG ELISA/high-titer capture) and immunoglobulin M (IgM) (Panbio(r)) antibodies.
The plaque reduction neutralization test (PRNT) was conducted on random samples
of IgG-positive sera for further confirmation. Medical history and a recall of
previous history of dengue were collected through interviews, whereas
sociodemographic information was obtained from an existing database. RESULTS: The
overall seroprevalence for DENV infection was 86.6% (240/277) (95% CI: 83-91%).
Serological evidence of recent infection (IgM/high-titer capture IgG) was noted
in 11.2% (31/277) of participants, whereas there was evidence of past infection
in 75.5% (209/277) of participants (indirect IgG minus recent infections). The
PRNT assay showed that the detected antibodies were indeed specific to DENV. The
multivariate analysis showed that the older age group was significantly
associated with past DENV infections. Seropositivity increased with age; 48.5% in
the age group of <25 years to more than 85% in age group of >45 years (P <
0.001). No associations with occupation, study site, housing type, comorbidity,
educational level, and marital status were observed, although the latter two were
statistically significant in the univariate analysis. None of the studied factors
were significantly associated with recent DENV infections in the multivariate
analysis, although there was a pattern suggestive of recent outbreak in two study
sites populated predominately by Chinese people. The majority of infections did
not give rise to recognizable disease (either asymptomatic or nonspecific
symptoms) as only 12.9% of participants (31/240) recalled having dengue in the
past. CONCLUSIONS: The predominantly rural community under study had a very high
previous exposure to dengue. The finding of a high proportion of unreported cases
possibly due to subclinical infections underscores the need for enhanced
surveillance and control methods. This finding also has implications for
measuring disease burden, understanding transmission dynamics, and hypothesizing
effects on DENV vaccine efficacy and uptake.
PMID- 29335023
TI - Early neonatal Glutaric aciduria type I hidden by perinatal asphyxia: a case
report.
AB - BACKGROUND: Perinatal asphyxia (PA) occurs in about 2 to 10 per 1000 live full
term births. Although neonatal epileptic seizures are observed in up to 60% of
cases, PA may mimic or subtend other conditions. Hypoxia related brain injury is
particularly relevant, as it may have permanent effects on neuropsychomotor
development. Antepartum obstetric conditions, may, in turn, lead to hypoxic
ischemic damage to the fetus and the newborn, often underlying PA. Herein, a case
of PA that hid and triggered signs and symptoms of Glutaric Aciduria type I (GA
I), is reported. CASE PRESENTATION: R.F. was born at term after prolonged labour,
by induced vaginal delivery with the Kristeller manoeuvre. He presented with
severe asphyxia and asystoly. Immediate cardiopulmonary resuscitation promptly
restored cardiorespiratory parameters, allowing for early extubation 30 min
after. During the following hours, severe axial muscle hypotonia with an
increased tone of the limb extensor muscles became evident. The absence of crying
and archaic reflexes persisted and there was an onset of generalized tonic or
clonic seizure. First level metabolic and inflammatory markers were within the
normal range. An inherited metabolic disease was then suspected, due to the
persistent clinical signs of severe neurological damage without any detectable
septic parameter. GA-I was assessed and specific treatment started without any
clinical improvement, although ensuring adequate growth and metabolic control.
Thereafter, the baby developed a severe encephalopathy with drug resistant
epileptic seizures. The progression of the neurological damage and a CVC-related
sepsis led him to exitus at 2 years. CONCLUSIONS: To the best of our knowledge,
this is the first case of early post-natal onset of GA-I reported in literature
to date, in the absence of expanded newborn screening (NBS) programme. As
expanded NBS programmes for inborn errors of metabolism have not yet been
internationally adopted, we are of the opinion that such diseases may well be
hidden by misleading signs and symptoms imputable to other more frequent harmful
clinical conditions. Moreover, it would be advisable that neonatologists be
trained to include GA-I in the differential diagnosis of neurological damage
secondary to PA.
PMID- 29335025
TI - Prevalence of a carbapenem-resistance gene (KPC), vancomycin-resistance genes
(van A/B) and a methicillin-resistance gene (mecA) in hospital and municipal
sewage in a southwestern province of Saudi Arabia.
AB - OBJECTIVE: According to the World Health Organization, the increasing antibiotic
resistance of pathogens is one of the most important threats to human health.
Prevalence of a carbapenem-resistance gene (KPC), vancomycin-resistance genes
(van A/B) and a methicillin-resistance gene (mecA) in hospital and municipal
sewages will be potential threat to public health. RESULTS: Vancomycin-resistance
genes were detected in the sewage of community tank-II, sewage tank of the
tertiary and general hospital. Carbapenem-resistance gene was detected in sewage
of community tank-II and sewage from tertiary hospital. Methicillin-resistance
gene was detected in sewage of community tank-II, sewage from a fish market
sewage tank and sewage from an animal slaughter house sewage tank. The detection
of a KPC, van A/B and a mecA in sewages will help further the process to take the
appropriate measures to prevent the spread of such bacteria in the environment.
PMID- 29335024
TI - Sex differences in the late first trimester human placenta transcriptome.
AB - BACKGROUND: Development of the placenta during the late first trimester is
critical to ensure normal growth and development of the fetus. Developmental
differences in this window such as sex-specific variation are implicated in later
placental disease states, yet gene expression at this time is poorly understood.
METHODS: RNA-sequencing was performed to characterize the transcriptome of 39
first trimester human placentas using chorionic villi following genetic testing
(17 females, 22 males). Gene enrichment analysis was performed to find enriched
canonical pathways and gene ontologies in the first trimester. DESeq2 was used to
find sexually dimorphic gene expression. Patient demographics were analyzed for
sex differences in fetal weight at time of chorionic villus sampling and birth.
RESULTS: RNA-sequencing analyses detected 14,250 expressed genes, with chromosome
19 contributing the greatest proportion (973/2852, 34.1% of chromosome 19 genes)
and Y chromosome contributing the least (16/568, 2.8%). Several placenta-enriched
genes as well as histone-coding genes were identified to be unique to the first
trimester and common to both sexes. Further, we identified 58 genes with
significantly different expression between males and females: 25 X-linked, 15 Y
linked, and 18 autosomal genes. Genes that escape X inactivation were highly
represented (59.1%) among X-linked genes upregulated in females. Many genes
differentially expressed by sex consisted of X/Y gene pairs, suggesting that
dosage compensation plays a role in sex differences. These X/Y pairs had roles in
parallel, ancient canonical pathways important for eukaryotic cell growth and
survival: chromatin modification, transcription, splicing, and translation.
CONCLUSIONS: This study is the first characterization of the late first trimester
placenta transcriptome, highlighting similarities and differences among the sexes
in ongoing human pregnancies resulting in live births. Sexual dimorphism may
contribute to pregnancy outcomes, including fetal growth and birth weight, which
was seen in our cohort, with males significantly heavier than females at birth.
This transcriptome provides a basis for development of early diagnostic tests of
placental function that can indicate overall pregnancy heath, fetal-maternal
health, and long-term adult health.
PMID- 29335026
TI - Congenital anomalies in neurofibromatosis 1: a retrospective register-based total
population study.
AB - BACKGROUND: Neurofibromatosis type 1 (NF1) is a dominantly inherited Rasopathy
caused by mutations in the NF1 gene on chromosome 17. NF1 has been connected to
congenital anomalies, e.g., in the skeletal and cardiovascular systems, but the
overall incidence of anomalies is unknown. In this retrospective register-based
total population study conducted in Finland, the congenital anomalies in NF1 were
evaluated. METHODS: One thousand four hundred ten patients with NF1 were
identified by searching the medical records related to inpatient and outpatient
hospital visits of patients with an associated diagnosis for NF1 in 1987-2011.
Each diagnosis was confirmed by a thorough review of the medical records. Ten non
NF1 control persons per NF1 patient were collected from the Population Register
Centre. NF1 patients and controls were linked to the Medical Birth Register and
the Register of Congenital Malformations. Odds ratios (OR) and 95% confidence
intervals (95% CI) for major congenital anomalies (MCA) were calculated. RESULTS:
The OR for at least one MCA among NF1 children was almost threefold (adjusted OR
2.78, 95% CI 1.71-4.54) compared to controls matched for age, sex and
municipality. NF1 children had a significantly increased risk of congenital
anomalies in the circulatory (adjusted OR 3.35, 95% CI 1.64-6.83), urinary
(adjusted OR 4.26, 95% CI 1.36-13.35) and musculoskeletal (adjusted OR 2.77, 95%
CI 1.09-7.02) systems. Also, anomalies of the eye, ear, head and neck were more
common among NF1 children than controls (adjusted OR 4.66, 95% CI 1.42-15.31).
Non-NF1 children of mothers with NF1 did not have more anomalies than controls
(adjusted OR 0.53, 95% CI 0.13-2.21). CONCLUSIONS: Children with NF1 have more
MCAs than controls and close follow-up during pregnancy and the neonatal period
is required if the mother or father has NF1. Non-NF1 children of mothers with NF1
do not have an increased risk for anomalies.
PMID- 29335028
TI - Towards a 21st century health care system: advancing the case for telecare.
AB - Telecare is increasingly recognized as an essential tool for a contemporary
twenty-first century health care system even though the evidence is still
emerging on its effectiveness. The need to find delivery models like telecare
that improve both the convenience and value of care is universal, but
particularly pressing for countries like the U.S. and Israel who are facing
rising costs related to the needs of individuals with multiple complex
conditions. This commentary provides highlights of the current state of practice
and policy for telecare and the challenges that remain ahead as it is adopted
into the mainstream.
PMID- 29335027
TI - Fungi stabilize connectivity in the lung and skin microbial ecosystems.
AB - BACKGROUND: No microbe exists in isolation, and few live in environments with
only members of their own kingdom or domain. As microbiome studies become
increasingly more interested in the interactions between microbes than in
cataloging which microbes are present, the variety of microbes in the community
should be considered. However, the majority of ecological interaction networks
for microbiomes built to date have included only bacteria. Joint association
inference across multiple domains of life, e.g., fungal communities (the
mycobiome) and bacterial communities, has remained largely elusive. RESULTS:
Here, we present a novel extension of the SParse InversE Covariance estimation
for Ecological ASsociation Inference (SPIEC-EASI) framework that allows
statistical inference of cross-domain associations from targeted amplicon
sequencing data. For human lung and skin micro- and mycobiomes, we show that
cross-domain networks exhibit higher connectivity, increased network stability,
and similar topological re-organization patterns compared to single-domain
networks. We also validate in vitro a small number of cross-domain interactions
predicted by the skin association network. CONCLUSIONS: For the human lung and
skin micro- and mycobiomes, our findings suggest that fungi play a stabilizing
role in ecological network organization. Our study suggests that computational
efforts to infer association networks that include all forms of microbial life,
paired with large-scale culture-based association validation experiments, will
help formulate concrete hypotheses about the underlying biological mechanisms of
species interactions and, ultimately, help understand microbial communities as a
whole.
PMID- 29335029
TI - Estimating the proportion of clinically diagnosed infectious and non-infectious
animal diseases in Ganta Afeshum woreda, Eastern Tigray zone, Ethiopia.
AB - OBJECTIVE: This study was performed with the objective of identifying the
proportion of emerging and endemic livestock diseases using cross sectional
survey. RESULT: A total of 285 clinically diseased animals were presented to a
veterinary clinic and diagnosed tentatively based on history, clinical sign, and
simple laboratory diagnostics and from the study, actinomycosis (15.83%),
mastitis (15%), tick infestation (10%), respiratory diseases (9.16%) and gastro
intestinal parasitism (9.16%) were confirmed with higher proportion in large
animals. Pasteurollosis (38, 31%), contagious ecthyma (12, 10%), tick infestation
(9, 0%), mite infestation (9, 10%), sheep and goat pox (9, 10%), and
gastrointestinal parasitism (9, 17%) were frequently encountered diseases in
sheep and goat respectively. In equids, back sore, epizootic lymphangitis and
lameness accounted a proportion of 22.95, 21.31, and 13.11% respectively. In
conclusion, result of the present study showed that the proportion of livestock
disease is high, and it affects the socioeconomic status of the local community
in the study area as a result of mortality and production loss.
PMID- 29335031
TI - Respiration pattern variability and related default mode network connectivity are
altered in remitted depression.
AB - BACKGROUND: Studies with healthy participants and patients with respiratory
diseases suggest a relation between respiration and mood. The aim of the present
analyses was to investigate whether emotionally challenged remitted depressed
participants show higher respiration pattern variability (RPV) and whether this
is related to mood, clinical outcome and increased default mode network
connectivity. METHODS: To challenge participants, sad mood was induced with
keywords of personal negative life events in individuals with remitted depression
[recurrent major depressive disorder (rMDD), n = 30] and matched healthy controls
(HCs, n = 30) during functional magnetic resonance imaging. Respiration was
measured by means of a built-in respiration belt. Additionally, questionnaires, a
daily life assessment of mood and a 3 years follow-up were applied. For
replication, we analysed RPV in an independent sample of 53 rMDD who underwent
the same fMRI paradigm. RESULTS: During sad mood, rMDD compared with HC showed
greater RPV, with higher variability in pause duration and respiration frequency
and lower expiration to inspiration ratio. Higher RPV was related to lower daily
life mood and predicted higher depression scores as well as relapses during a 3
year follow-up period. Furthermore, in rMDD compared with HC higher main
respiration frequency exhibited a more positive association with connectivity of
the posterior cingulate cortex and the right parahippocampal gyrus. CONCLUSIONS:
The results suggest a relation between RPV, mood and depression on the
behavioural and neural level. Based on our findings, we propose interventions
focusing on respiration to be a promising additional tool in the treatment of
depression.
PMID- 29335030
TI - Preschool psychiatric disorders: homotypic and heterotypic continuity through
middle childhood and early adolescence.
AB - BACKGROUND: Many preschool-age children meet criteria for psychiatric disorders,
and rates approach those observed in later childhood and adolescence. However,
there is a paucity of longitudinal research examining the outcomes of preschool
diagnoses. METHODS: Families with a 3-year-old child (N = 559) were recruited
from the community. Primary caregivers were interviewed using the Preschool Age
Psychiatric Assessment when children were 3 years old (n = 541), and, along with
children, using the Schedule for Affective Disorders and Schizophrenia for School
Age Children Present and Lifetime Version when children were 9 and 12 years old.
RESULTS: Rates of disruptive behavior disorders (DBD) decreased from preschool to
middle childhood and early adolescence, whereas rates of attention
deficit/hyperactivity disorder (ADHD) increased. Rates of any psychiatric
disorder and depression increased from preschool to early adolescence only.
Preschoolers with a diagnosis were over twice as likely to have a diagnosis
during later periods. Homotypic continuity was present for anxiety disorders from
preschool to middle childhood, for ADHD from preschool to early adolescence, and
for DBD through both later time points. There was heterotypic continuity between
preschool anxiety and early adolescent depression, and between preschool ADHD and
early adolescent DBD. Dimensional symptom scores showed homotypic continuity for
all diagnostic categories and showed a number of heterotypic associations as
well. CONCLUSIONS: Results provide moderate support for the predictive validity
of psychiatric disorders in preschoolers. Psychopathology in preschool is a
significant risk factor for future psychiatric disorders during middle childhood
and early adolescence.
PMID- 29335033
TI - Should capacity assessments be performed routinely prior to discussing advance
care planning with older people?
AB - : ABSTRACTBackground:People with dementia receive worse end of life care compared
to those with cancer. Barriers to undertaking advanced care planning (ACP) in
people with dementia include the uncertainty about their capacity to engage in
such discussions. The primary aim of this study was to compare the Advance Care
Planning-Capacity Assessment Vignette tool (ACP-CAV) with a semi-structured
interview adapted from the MacArthur Competence Assessment Tool-Treatment (MacCAT
T). The secondary aim was to identify demographic and cognitive functioning
variables that may predict whether a person has capacity to discuss ACP. METHODS:
32 older people (mean age = 84.1) with a Mini-Mental State Examination of 24 or
above were recruited from two retirement villages in Auckland. Participants also
completed Trail Making Test Part A & Part B and Geriatric Depression Scale (GDS
15) before undertaking the two capacity assessments that were video recorded to
enable further analysis by four independent old age psychiatrists. RESULTS: Using
the MacCAT-T as the gold standard, over half (53.1%) of the participants were
considered as lacking in capacity to engage in ACP. Participants struggled with
the "Understanding ACP" domain the most. Capacity was not predictable by any of
the demographic or cognitive functioning variables. When compared to the gold
standard, ACP-CAV was accurate in assessing capacity in 68.8% of the cases.
CONCLUSION: Clinicians should routinely explain ACP to older people and ensure
they fully understand it prior to an ACP discussion. If there is any concern
about their understanding, further exploration and documentation of their
capacity using the capacity assessment framework would be necessary. However,
capacity assessment is a complex iterative process that does not easily lend
itself to screening methodology and requires a high level of clinical judgment.
PMID- 29335032
TI - 'Sit and tilt' preparation for subscapular system free flaps.
AB - BACKGROUND: The ablation of advanced head and neck cancer often results in large
three-dimensional defects that require free tissue transfer to optimally address
functional and cosmetic issues. The subscapular system is a highly versatile
donor site for flaps used for head and neck reconstruction. Traditional methods
of harvesting subscapular flaps require repositioning and re-preparing, which
significantly increases the operative time and prevents simultaneous harvesting
of the flap. METHOD: This paper presents our experience of a single-stage 'sit
and tilt' technique, which provides a convenient method for harvesting
subscapular system free flaps without significant repositioning. RESULTS AND
CONCLUSION: This technique was used for a variety of head and neck defects, and
body habitus did not seem to affect free tissue harvesting. It is hoped that
utilisation of this preparation and harvesting technique will make head and neck
surgeons more willing to take advantage of the subscapular system.
PMID- 29335034
TI - Staying Out of the Closet: LGBT Older Adults' Hopes and Fears in Considering End
of-Life.
AB - Canada is experiencing population aging, and given the heterogeneity of older
adults, there is increasing diversity in late life. The purpose of this study was
to help fill the research gaps on LGBT aging and end-of-life. Through focus
groups, we sought to better understand the lived experience of older LGBT
individuals and to examine their concerns associated with end-of-life. Our
analysis highlights the idea that identifying as LGBT matters when it comes to
aging and end-of-life care. In particular, gender identity and sexual orientation
matter when it comes to social connections, in the expectations individuals have
for their own care, and in the unique fear related to staying out of the closet
and maintaining identity throughout aging and end-of-life. This study underscores
the need to consider gender identity and sexual orientation at end-of-life. In
particular, recognition of intersectionality and social locations is crucial to
facilitating positive aging experiences and end-of-life care.
PMID- 29335035
TI - Innovating dementia care; implementing characteristics of green care farms in
other long-term care settings.
AB - : ABSTRACTBackground:People with dementia at green care farms (GCFs) are
physically more active, have more social interactions, are involved in a larger
variety of activities, and come outdoors more often than those in other long-term
dementia care settings. These aspects may positively affect health and well
being. This study explored which and how characteristics of GCFs could be
implemented in other long-term dementia care settings, taking into account
possible facilitators and barriers. METHODS: Semi-structured interviews were
conducted with 23 professionals from GCFs, independent small-scale long-term care
facilities, and larger scale long-term care facilities in the Netherlands. The
framework method was used to analyze the data. RESULTS: Several characteristics
of GCFs (e.g. homelike aspects, domestic activities, and access to outdoor
environments) have already been applied in other types of long-term dementia care
settings. However, how and the extent to which these characteristics are being
applied differ between GCFs and other types of long-term dementia care settings.
Facilitators and barriers for the implementation of characteristics of GCFs were
related to the physical environment in which the care facility is situated (e.g.
the degree of urbanization), characteristics and competences of staff members
(e.g. flexibility, creativity), characteristics and competences of managers (e.g.
leadership, vision), and the political context (e.g. application of risk and
safety protocols). CONCLUSION: Several characteristics can be implemented in
other dementia care settings. However, to realize innovation in dementia care it
is important that not only the physical environment but also the social and
organizational environments are supporting the process of change.
PMID- 29335036
TI - Individuals with currently untreated mental illness: causal beliefs and readiness
to seek help.
AB - AIMS: Many people with mental illness do not seek professional help. Beliefs
about the causes of their current health problem seem relevant for initiating
treatment. Our aim was to find out to what extent the perceived causes of current
untreated mental health problems determine whether a person considers
herself/himself as having a mental illness, perceives need for professional help
and plans to seek help in the near future. METHODS: In a cross-sectional study,
we examined 207 untreated persons with a depressive syndrome, all fulfilling
criteria for a current mental illness as confirmed with a structured diagnostic
interview (Mini International Neuropsychiatric Interview). The sample was
recruited in the community using adverts, flyers and social media. We elicited
causal explanations for the present problem, depression literacy, self
identification as having a mental illness, perceived need for professional help,
help-seeking intentions, severity of depressive symptoms (Patient Health
Questionnaire - Depression), and whether respondents had previously sought mental
healthcare. RESULTS: Most participants fulfilled diagnostic criteria for a mood
disorder (n = 181, 87.4%) and/or neurotic, stress-related and somatoform
disorders (n = 120, 58.0%) according to the ICD-10. N = 94 (45.4%) participants
had never received mental health treatment previously. Exploratory factor
analysis of a list of 25 different causal explanations resulted in five factors:
biomedical causes, person-related causes, childhood trauma, current stress and
unhealthy behaviour. Attributing the present problem to biomedical causes, person
related causes, childhood trauma and stress were all associated with stronger
self-identification as having a mental illness. In persons who had never received
mental health treatment previously, attribution to biomedical causes was related
to greater perceived need and stronger help-seeking intentions. In those with
treatment experience, lower attribution to person-related causes and stress were
related to greater perceived need for professional help. CONCLUSIONS: While
several causal explanations are associated with self-identification as having a
mental illness, only biomedical attributions seem to be related to increase
perceived need and help-seeking intentions, especially in individuals with no
treatment experiences. Longitudinal studies investigating causal beliefs and help
seeking are needed to find out how causal attributions guide help-seeking
behaviour. From this study it seems possible that portraying professional mental
health treatment as not being restricted to biomedical problems would contribute
to closing the treatment gap for mental disorders.
PMID- 29335037
TI - Is freedom (still) therapy? The 40th anniversary of the Italian mental health
care reform.
AB - On 13 May 1978, the Italian Parliament approved Law 180, universally known as
'Basaglia Law' after the name of the leader of the anti-institutional movement
which promoted this radical community mental health care reform. Forty years
later, Italian psychiatry still runs a community care system, albeit with degrees
of solidity and quality very varied along the peninsula. Mental health care is
still an integral part of the National Health System, with liberal regulations on
coercion and a lowest number of general hospital and residential facilities beds.
Recently, Italy has also closed the special forensic psychiatric institutions and
brought the care of the mentally ill offenders within the responsibilities of
local Mental Health Departments. Over time, psychiatric deinstitutionalisation
inspired policies in other sectors of Italian society, such as those regarding
physical and intellectual disabilities, education of children with special needs,
drug addictions and management of deviant minors. Furthermore, debate about Law
180 has reached and maintained an international dimension, becoming a term of
reference for international agencies such as the World Health Organization and
the European Commission, for good and for evil. The overall balance sheet of the
Reform process would seem mostly positive, though the last decade has seen many
threats challenging the system. Mental health care services have been asked to do
much more, in terms of care to a larger population with very diversified needs,
but with much less resources, due to the financial consequences of the economic
crisis. Although there is no evidence of a trend towards re-institutionalisation,
intensity and quality of care may have fallen below acceptable standards in some
parts of Italy.
PMID- 29335038
TI - What is the prevalence of untreated depression and death ideation in older
people? Data from the Irish Longitudinal Study on Aging.
AB - : ABSTRACTObjective:Late life depression (LLD) confers significant morbidity and
mortality but is well recognized that it often goes undetected or untreated. The
objective of this study is to quantify the burden of untreated depression and
death ideation (DI) at a population level. DESIGN: Cross-sectional study
ascertaining the prevalence of, and factors associated with, untreated depression
and DI. SETTING: This study, embedded within the Irish Longitudinal Study on
Ageing, involves over 7,000 community-dwelling people aged >=50 years.
MEASUREMENTS: Depression was defined as Centre for Epidemiological Studies
Depression scale >=16 indicating current clinically relevant depressive symptoms
or Composite International Diagnostic Interview indicative of major depressive
episode within the last year. Participants not prescribed
antidepressants/antipsychotics were defined as untreated. To define DI,
participants were asked "In the last month, have you felt like you would rather
be dead?" RESULTS: In total, 12% (839/7,055) met criteria for depression with 29%
(241/839) on pharmacological therapy. Those with untreated depression were less
likely to endorse symptoms of persistent low mood or worthlessness, but there was
no difference in age or general practitioner (GP) visits compared to those on
treatment. Over 3% (223/7,055) of participants had DI and less than one-third had
visited their GP within the last year. CONCLUSIONS: This study demonstrates that
two-thirds of depressed older people are not prescribed
antidepressant/antipsychotic therapy. It is important to raise awareness of
depression among older people and healthcare professionals, with particular focus
on the fact that LLD is not an inevitable consequence of ageing and effective
treatment is available.
PMID- 29335039
TI - Replacing carbohydrate during a glucose challenge with the egg white portion or
whole eggs protects against postprandial impairments in vascular endothelial
function in prediabetic men by limiting increases in glycaemia and lipid
peroxidation.
AB - Eggs attenuate postprandial hyperglycaemia (PPH), which transiently impairs
vascular endothelial function (VEF). We hypothesised that co-ingestion of a
glucose challenge with egg-based meals would protect against glucose-induced
impairments in VEF by attenuating PPH and oxidative stress. A randomised, cross
over study was conducted in prediabetic men (n 20) who ingested isoenegertic
meals (1674 kJ (400 kcal)) containing 100 g glucose (GLU), or 75 g glucose with
1.5 whole eggs (EGG), seven egg whites (WHITE) or two egg yolks (YOLK). At 30 min
intervals for 3 h, brachial artery flow-mediated dilation (FMD), plasma glucose,
insulin, cholecystokinin (CCK), lipids (total, LDL- and HDL-cholesterol; TAG), F2
isoprostanes normalised to arachidonic acid (F2-IsoPs/AA), and methylglyoxal were
assessed. In GLU, FMD decreased at 30-60 min and returned to baseline levels by
90 min. GLU-mediated decreases in FMD were attenuated at 30-60 min in EGG and
WHITE. Compared with GLU, FMDAUC was higher in EGG and WHITE only. Relative to
baseline, glucose increased at 30-120 min in GLU and YOLK but only at 30-90 min
in EGG and WHITE. GlucoseAUC and insulinAUC were also lower in EGG and WHITE
only. However, CCKAUC was higher in EGG and WHITE compared with GLU. Compared
with GLU, F2-IsoPs/AAAUC was lower in EGG and WHITE but unaffected by YOLK.
Postprandial lipids and methylglyoxal did not differ between treatments. Thus,
replacing a portion of a glucose challenge with whole eggs or egg whites, but not
yolks, limits postprandial impairments in VEF by attenuating increases in
glycaemia and lipid peroxidation.
PMID- 29335040
TI - Does a cognitive stress test predict progression from mild cognitive impairment
to dementia equally well in clinical versus population-based settings?
AB - : ABSTRACTBackground:Evidence suggests that semantic interference may be a
sensitive indicator of early dementia. We examined the utility of the Semantic
Interference Test (SIT), a cognitive stress memory paradigm which taps proactive
and retroactive semantic interference, for predicting progression from mild
cognitive impairment (MCI) to dementia in both a clinical and a population-based
sample. METHODS: Participants with MCI in the clinical (n = 184) and population
based (n = 435) samples were followed for up to four years. We employed receiver
operating characteristic (ROC) methods to establish optimal thresholds for four
different SIT indices. Threshold performance was compared in the two samples
using logistic and Cox proportional hazard regression models. RESULTS: Within
four years, 42 (22.8%) MCI individuals in the clinical sample and 45 (10.3%)
individuals in the population-based sample progressed to dementia. Overall
classification accuracy of SIT thresholds ranged from 61.4% to 84.8%. Different
subtests of the SIT had slightly different performance characteristics in the two
samples. However, regression models showed that thresholds established in the
clinical sample performed similarly in the population sample before and after
adjusting for demographics and other baseline neuropsychological test scores.
CONCLUSIONS: Despite differences in demographic composition and progression
rates, baseline SIT scores predicted progression from MCI to dementia similarly
in both samples. Thresholds that best predicted progression were slightly below
thresholds established for distinguishing between amnestic MCI and cognitively
normal subjects in clinical practice. This confirms the utility of the SIT in
both clinical and population-based samples and establishes thresholds most
predictive of progression of individuals with MCI.
PMID- 29335042
TI - Training and assessment in functional endoscopic sinus surgery.
AB - BACKGROUND: Functional endoscopic sinus surgery is a common procedure performed
within otolaryngology, but it carries potential for significant life-changing
complications. It is therefore essential that trainees undergo adequate training.
The European Working Time Directive has led to reduced operating time for the
trainee surgeon. With variable access and the cost implications associated with
cadaveric specimens, simulation can be an invaluable educational resource in
surgical training. The current literature regarding the various simulation
methodologies that have been used in functional endoscopic sinus surgery training
is discussed. METHOD: A literature search was conducted using the key words
'nasal', 'nasal polyps', 'endoscope', 'education and simulation', 'endoscopic
sinus surgery' and 'training'. RESULTS: Twelve articles were identified; of
these, eight trialled the use of simulators, two utilised ovine models and two
used task trainers. CONCLUSION: Simulation has shown benefit in functional
endoscopic sinus surgery training; however, a robust platform accessible to ENT
trainees is lacking.
PMID- 29335041
TI - Clinical correlates of resilience factors in geriatric depression.
AB - BACKGROUND: Traditional perspectives conceptualize resilience as a trait and
depression as resulting from resilience deficiency. However, research indicates
that resilience varies substantially even among adults who are clinically
depressed, as well as across the lifespan of an individual. Few studies have
investigated resilience in depression, and even fewer have examined resilience in
depressed older adults. METHODS: Three hundred thirty-seven adults >=60 years
with major depressive disorder completed the Connor-Davidson Resilience Scale (CD
RISC) and measures of mental health, quality of life (QOL), and medical
comorbidity. Exploratory factor analysis was used to explore the factor structure
of the CD-RISC. Correlations and general linear models were used to examine
associations between resilience and other variables. RESULTS: The rotated
component matrix indicated a four-factor model. Sorting of items by highest
factor loading revealed constructs associated with (1) grit, (2) active coping
self-efficacy, (3) accommodative coping self-efficacy, and (4) spirituality.
Resilience was significantly correlated with increased age, lower cognitive
functioning, greater cerebrovascular risk, and greater medical comorbidity.
Resilience was negatively associated with mental health symptoms (depression,
apathy, and anxiety) and positively associated with QOL. The final optimal model
identified less depression, less apathy, greater medical comorbidity, higher QOL,
and minority (non-White) race as factors that significantly explained variability
in resilience. CONCLUSIONS: Resilience was significantly associated with a range
of mental health constructs in a sample of older adults with depression. Future
clinical trials and dismantling studies may help determine whether interventions
targeting grit, active coping, accommodative coping, and spirituality can
increase resilience and help prevent and treat depression in older adults.
PMID- 29335043
TI - Stentless mirrored L-shaped septonasal flap versus stented flapless technique for
endoscopic endonasal repair of bilateral congenital choanal atresia: a
prospective randomised controlled study.
AB - OBJECTIVES: To compare the outcomes of endoscopic repair of bilateral congenital
choanal atresia using a flap technique without stenting versus endoscopic repair
using stenting without a flap. METHODS: A prospective randomised controlled study
was conducted, comprising 72 patients with bilateral congenital choanal atresia.
The patients were randomised into two groups. Group A (42 patients) underwent
endoscopic repair using a mirrored L-shaped flap without stenting, and group B
(30 patients) underwent endoscopic repair using stenting without a flap. RESULTS:
At a mean follow-up period of 18.2 months, endoscopic assessment revealed a
patent posterior choana in 81 per cent and 83.33 per cent of patients in group A
and group B respectively. Choanal stenosis occurred in 21.40 per cent and 33.33
per cent of patients in group A and group B respectively. Granulation tissue was
observed in 28.6 per cent and 53.3 per cent of patients in group A and group B
respectively. CONCLUSION: The endoscopic approach utilising a flap without
stenting is safe and effective, with a high success rate.
PMID- 29335044
TI - Leges Sine Moribus Vanae.
PMID- 29335045
TI - Letter to the Editor.
PMID- 29335047
TI - Money in Tension with Ethics: A Commentary.
AB - Monetary incentives are frequently in tension with evidence-based and cost
effective clinical care, thus posing an ethical concern in the practice of
dentistry. The purpose of this commentary was to examine the issue of treating
children in the context of caries risk assessment and with specific reference to
the periodic oral examination, radiographic surveillance, topical fluorides, and
the pumice rubber prophylaxis.
PMID- 29335048
TI - Antiplaque, Antifungal Effectiveness of Aloevera Among Intellectually Disabled
Adolescents: Pilot Study.
AB - PURPOSE: Various candida species have been associated with poor oral hygiene and
active carious lesions. The purpose of this study was to evaluate the
effectiveness of aloe vera compared to triclosan toothpaste against total
candida, C. albicans, C. tropicalis, Candida krusei, and plaque/gingivitis among
intellectually disabled adolescents over 30 days. METHODS: A double-blind
prospective randomized trial was conducted among 40 intellectually disabled
adolescents randomly allocated into aloe vera/triclosan groups. The gingival (Loe
and Silness index), plaque (Silness and Loe index), and candidal carriage counts
were assessed at baseline and follow-up. Caregivers brushed the participant's
teeth twice a day using a modified bass method and refrained from any other oral
hygiene practices for at least two hours prior to assessment. RESULTS: Aloe vera
contaiing toothpaste caused significant reductions in gingival inflammation and
plaque index scores compared to the triclosan group at the end of 30 days. Also,
total candidal counts and C. albicans counts were significantly lower in the aloe
vera group compared to triclosan at the end of the 30-day follow-up (P<0.05).
CONCLUSION: Aloe vera-containing toothpaste was effective in reducing plaque,
gingivitis, and overall candidal counts compared to triclosan. Moreover,
individuals treated with aloe vera experienced improved oral health status
without any negative side effects.
PMID- 29335049
TI - Dental Treatment and Expenditures Under General Anesthesia Among Medicaid
Enrolled Children in North Carolina.
AB - PURPOSE: Many studies reporting dental utilization under general anesthesia (GA)
are dated. The purpose of this study was to provide contemporaneous data about
children receiving dental GA by: (1) determining trends in utilization and
associated expenditures; and (2) examining the effects of provider distribution.
METHODS: This time series cross-sectional study of Medicaid-eligible children
ages zero to eight years old in North Carolina used aggregate Medicaid claims
from State Fiscal Years (SFY) 2011 to 2015 to collect demographic and dental
treatment information. Descriptive statistics were stratified by age and year to
examine trends over time. Panel analysis techniques were used to explore regional
effects of provider distribution on dental GA utilization. RESULTS: For SFY 2011
to 2015, the overall dental utilization rate was 517.1 per 1,000 (total enrolled
equals 632,941 children/year), and the dental GA utilization rate was 15.8 per
1,000. Total dental expenditures averaged $113 million per year, and dental GA
averaged $16.7 million per year. The dental GA proportion of expenditures
increased over time (P<.001). Provider distribution did not affect dental GA
utilization rate (P=.178) but did increase the number of children receiving
dental GA (P<.001). CONCLUSIONS: Utilization and expenditures associated with
dental treatment under general anesthesia continue to increase. While this
reflects increased access to care, interventions should be examined to provide
preventive care earlier in a child's life.
PMID- 29335050
TI - Are Hypomineralized Primary Molars and Canines Associated with Molar-Incisor
Hypomineralization?
AB - PURPOSE: The purpose of this study was to evaluate the prevalence of and
relationship between hypomineralized second primary molars (HSPM) and
hypomineralized primary canines (HPC) with molar-incisor hypomineralization (MIH)
in 1,963 schoolchildren. METHODS: The European Academy of Paediatric Dentistry
(EAPD) criterion was used for scoring HSPM/HPC and MIH. Only children with four
permanent first molars and eight incisors were considered in calculating MIH
prevalence (n equals 858); for HSPM/HPC prevalence, only children with four
primary second molars (n equals 1,590) and four primary canines (n
equals 1,442) were considered. To evaluate the relationship between MIH/HSPM,
only children meeting both criteria cited were considered (n equals 534), as was
true of MIH/HPC (n equals 408) and HSPM/HPC (n equals 360; chi
square test and logistic regression). RESULTS: The prevalence of MIH was 14.69
percent (126 of 858 children). For HSPM and HPC, the prevalence was 6.48 percent
(103 of 1,592) and 2.22 percent (32 of 1,442), respectively. A significant
relationship was observed between MIH and both HSPM/HPC (P<0.001). The odds ratio
for MIH based on HSPM was 6.31 (95 percent confidence interval [CI] equals 2.59
to 15.13) and for HPC was 6.02 (95 percent CI equals 1.08 to 33.05). CONCLUSION:
The results led to the conclusion that both hypomineralized second primary molars
and hypomineralized primary canines are associated with molar-incisor
hypomineralization, because children with HSPM/HPC are six times more likely to
develop MIH.
PMID- 29335051
TI - Effectiveness of a Preventive Recall Strategy for Children After Dental
Rehabilitation with General Anesthesia.
AB - PURPOSE: To test a more frequent preventive recall strategy following full-mouth
dental rehabilitation (FMDR) in children with early childhood caries (ECC).
METHODS: Patients were randomized into two groups: controls, who were scheduled
to return at six-month intervals (6-MR); and the intervention group, who were
scheduled to return at three-month intervals (3-MR and 6-MR). At baseline and at
each recall, a caries risk assessment (CRA) and dental exam were completed.
Analyses followed CONSORT recommendations, resulting in three analyses: intent-to
treat; per-protocol; and an actual recall analysis. RESULTS: Intent-to-treat
analysis showed no significant difference in CRA at six months (P>0.7); per
protocol analysis showed borderline significance (P>.08); and actual recall
analysis showed a statistically significant difference in CRA at six months
(P=.021). For patients with both 3-MR and 6-MR, 44 percent were assessed at a
high caries risk level; for patients with only a 6-MR, 72 percent were assessed
as a high caries risk level (P=.021). No significant differences were found in
caries incidence at six months. CONCLUSIONS: Following full-mouth dental
rehabilitation, patients who returned for follow-ups at both three- and six-month
intervals had a greater decrease in caries risk level compared to patients seen
at six-month follow-up intervals.
PMID- 29335052
TI - An Evaluation of Bite Pattern in Children with Severe-Early Childhood Caries
Before and After Complete Dental Rehabilitation.
AB - PURPOSE: The purpose of this study was to examine the changes in bite
characteristics of children before and after the placement of multiple stainless
steel crowns (SSCs) under general anesthesia (GA). METHODS: Twenty children
scheduled for treatment under general anesthesia who needed SSCs in three or more
posterior quadrants were included in this study. The bite was digitally analyzed
and recorded preoperatively and at one and four weeks postoperatively. The
occlusion time, number of force outliers, and distribution of force at each visit
was recorded and compared. RESULTS: The placement of the SSCs in children
significantly improved the bite characteristics of the participants. The
placement of the SSC did not alter occlusion time, and there were no significant
differences in occlusion time. While there was an increase in the number of
outliers in the first week after the placement of the crown, there was a
reduction in the total number of outliers at the end of one month. All the
patients treated with bilateral placement of an SSC showed a posterior balanced
occlusion post-operatively, a finding that was retained over the one-month follow
up period. CONCLUSION: Bilateral placement of SSCs under general anesthesia does
not significantly alter the occlusion of the child.
PMID- 29335053
TI - Facial Nerve Paresis: Case Report of Blunt Facial Nerve Injury.
AB - Facial nerve paresis is an uncommon but concerning condition in the pediatric
population. The function and anatomy of the facial nerve is complex, and injuries
to this structure may be associated with devastating physiological and
psychological implications for the affected child and family. The purpose of this
paper was to report a case involving a six-year-old Caucasian female who suffered
a blunt traumatic injury to the orofacial region resulting in partial paralysis
of the seventh cranial nerve. Following the injury, the child was unable to fully
elevate the corner of her mouth. The deficit occurred immediately, and she
experienced a prolonged course of recovery.
PMID- 29335054
TI - Orbital, Mediastinal and Cervicofacial Subcutaneous Emphysema after Dental
Rehabilitation in a Pediatric Patient.
AB - Subcutaneous emphysema is a rare possible complication of dental procedures. The
majority of the dental literature describes cases of localized areas of
subcutaneous emphysema following various dental procedures, with a large number
of these cases seen following intraoral surgical procedures. Classically,
subcutaneous emphysema occurs within minutes to hours after conclusion of dental
procedures and is commonly misdiagnosed as either an allergic reaction or acute
post-operative swelling. This case report describes a four-year-old male who
underwent dental rehabilitation for routine restorative dentistry without
extractions under general anesthesia. He subsequently developed extensive
subcutaneous emphysema involving the right periorbital region, cervicofacial
spaces, and caudal extension to include the superior aspect of the mediastinum.
The purpose of this report was to provide a brief review of the prior literature
on the subject, report on the case, and review the management for patients with
subcutaneous emphysema.
PMID- 29335056
TI - Vegetable and Fruit Consumption among Chinese Adults and Associated Factors: A
Nationally Representative Study of 170,847 Adults.
AB - OBJECTIVE: This study examined vegetable and fruit (VF) consumption rate and its
associated factors among Chinese adults. METHODS: Nationally representative data
from the 2013 China Chronic Disease Surveillance survey were used. Dietary intake
data, including VF consumption during the last 12 months, were collected. All
analyses were weighted to obtain nationally representative estimates.
Associations between VF consumption and other factors (e.g., meal frequency and
physical activity) were examined through logistic regression analysis. RESULTS:
The average fruit consumption was 102.3 g/day (95% CI: 97.0-107.6) and the
average vegetable consumption was 350.6 g/day (95% CI: 339.3-361.8). Over half
(53.2%, 95% CI: 50.9-55.4) of Chinese adults met the VF consumption of 400 g/day
recommended by the World Health Organization (WHO). Rural residents had a higher
prevalence of low VF consumption rate than urban residents [49.20% (95% CI: 46.2%
52.2%) vs. 44.0% (95% CI: 41.7%-46.3%) P < 0.01]. Old age (OR = 1.01, 95% CI:
1.00-1.01), low educational level, low income, minority ethnicity (OR = 1.41, 95%
CI: 1.15-1.74), underweight (OR = 1.17, 95% CI: 1.03-1.33), single marital status
(OR = 1.20, 95% CI: 1.08-1.33), low health literacy, irregular breakfast (OR =
1.20, 95% CI: 1.04-1.38) or lunch (OR = 1.58, 95% CI: 1.26-1.99) habits, and no
leisure-time physical activity were associated with low VF consumption.
CONCLUSION: Only half of Chinese adults met the VF consumption recommended by the
WHO. Low socio-economic status, irregular diet, and poor health literacy were
likely associated with low VF consumption. National efforts and programs are
needed to promote VF consumption.
PMID- 29335057
TI - Study on the Simultaneously Quantitative Detection for beta-Lactoglobulin and
Lactoferrin of Cow Milk by Using Protein Chip Technique.
AB - OBJECTIVE: To research a protein chip method which can simultaneously
quantitative detect beta-Lactoglobulin (beta-L) and Lactoferrin (Lf) at one time.
METHODS: Protein chip printer was used to print both anti-beta-L antibodies and
anti-Lf antibodies on each block of protein chip. And then an improved sandwich
detection method was applied while the other two detecting antibodies for the two
antigens were added in the block after they were mixed. The detection conditions
of the quantitative detection for simultaneous measurement of beta-L and Lf with
protein chip were optimized and evaluated. Based on these detected conditions,
two standard curves of the two proteins were simultaneously established on one
protein chip. Finally, the new detection method was evaluated by using the
analysis of precision and accuracy. RESULTS: By comparison experiment, mouse
monoclonal antibodies of the two antigens were chosen as the printing probe. The
concentrations of beta-L and Lf probes were 0.5 mg/mL and 0.5 mg/mL,
respectively, while the titers of detection antibodies both of beta-L and Lf were
1:2,000. Intra- and inter-assay variability was between 4.88% and 38.33% for all
tests. The regression coefficients of protein chip comparing with ELISA for beta
L and Lf were better than 0.734, and both of the two regression coefficients were
statistically significant (r = 0.734, t = 2.644, P = 0.038; and r = 0.774, t =
2.998, P = 0.024). CONCLUSION: A protein chip method of simultaneously
quantitative detection for beta-L and Lf has been established and this method is
worthy in further application.
PMID- 29335058
TI - Association of Dietary Pattern during Pregnancy and Gestational Diabetes
Mellitus: A Prospective Cohort Study in Northern China.
AB - OBJECTIVE: To examine the association of maternal dietary patterns during
pregnancy with gestational diabetes mellitus (GDM) in northern China. METHODS:
The dietary intakes of pregnant women were recorded twice by 24-hour dietary
recalls for three days prior to having been diagnosed with GDM, at 5-15 and 24-28
gestational weeks, respectively. GDM was diagnosed, and serum glycosylated
hemoglobin (HbA1c) was measured at 24-28 weeks. Dietary patterns were assessed by
factor analysis. The association of the dietary pattern with GDM and HbA1c was
examined by multiple logistic models. RESULTS: Of 753 participants, 64 (8.5%)
were diagnosed with GDM. Four dietary patterns were identified: Western pattern
(dairy, baked/fried food and white meat), traditional pattern (light-colored
vegetables, fine grain, red meat and tubers), mixed pattern (edible fungi,
shrimp/shellfish and red meat) and prudent pattern (dark-colored vegetables and
deep-sea fish). Compared with the prudent pattern, both the Western pattern and
the traditional pattern were associated with an increased risk of GDM (aOR =
4.40, 95% CI: 1.58-12.22; aOR = 4.88, 95% CI: 1.79-13.32) and a high level of
HbA1c (aOR = 12.37, 95% CI: 1.47-103.91; aOR = 26.23, 95% CI: 2.54-270.74).
Compared to the lowest quartile (Q), Q3 of the Western pattern scores and Q3-Q4
of the traditional pattern scores were associated with a higher risk of GDM.
CONCLUSION: The consumption of the Western pattern or the traditional pattern
during pregnancy may increase the risk of GDM.
PMID- 29335059
TI - Association of alpha2A-Adrenergic Receptor Genetic Variants with Platelet
Reactivity in Chinese Patients on Dual Antiplatelet Therapy Undergoing
Percutaneous Coronary Intervention.
AB - OBJECTIVE: The alpha 2A-adrenergic receptor gene (ADRA2A) polymorphism in
individuals modifies the antiplatelet response to sympathetic stimulation. The
aim of this study was to investigate the effect of ADRA2A variants on platelet
reactivity in Chinese patients on dual antiplatelet therapy (DAPT) after
undergoing percutaneous coronary intervention (PCI). METHODS: From March 2011 to
March 2013, 1,024 patients were enrolled in this prospective, single-center,
observational study in China. Four single nucleotide polymorphisms (SNPs) of
ADRA2A gene (rs11195419, rs3750625, rs13306146, and rs553668) and CYP2C19*2 were
detected by ligase detection reaction (LDR), and adenosine diphosphate (ADP)
inhibition was detected by thromboelastography (TEG(r)). RESULTS: The minor
allele frequencies of ADRA2A SNPs were common. Platelet ADP inhibition was
significantly different among patients carrying rs11195419 (adjusted P = 0.022)
and rs3750625 (adjusted P = 0.016). The homozygous allele carriers had the lowest
ADP inhibition. However, ADP inhibition was not significantly different in
rs553668 and rs13306146. At the multivariate analysis, rs11195419 (P = 0.033),
rs3750625 (P = 0.020) and CYP2C19*2 (P = 0.002) were independent predictors of
ADP inhibition. Subgroups analysis based on sex showed rs11195419 (P = 0.003) and
rs3750625 (P = 0.002) were significantly associated with ADP inhibition in males,
but not in females. CONCLUSION: ADRA2A genetic variations were associated with
ADP-induced platelet aggregation during DAPT in Chinese patients undergoing PCI,
and the effect was particularly more pronounced in males.
PMID- 29335060
TI - Characteristics of Long-term Nonprogressors and Viremia Controllers Infected with
HIV-1 via Contaminated Blood Donations or Transfusions Conducted 20 Years
Earlier.
AB - To characterize long-term nonprogressors (LTNPs) and viremia controllers (VCs),
infected with HIV-1 through contaminated blood donation or transfusion between
1992 and 1996 in Henan, China. LTNPs and VCs were defined by CD4+T lymphocyte
(CD4) count and viral load (VL). Of 29,294 patients infected with HIV-1 via
contaminated blood donation or transfusion that had conducted for more than 20
years, 92 were LTNPs/VCs. There were 70 LTNPs (0.24%), 43 VCs (0.15%), and 48
LTNPs+VCs- (0.16%). VCs had a significantly lower CD4 nadir, compared to LTNPs
and LTNPs+VCs-, and no significant differences for the highest VL and HIV-1 DNA.
Cases P4 and P5 were LTNPs, while their VL reached approximately 4.3 log
copies/mL. P6 was a VC, but with CD4 < 500 cells/MUL constantly. Data from the
LTNPs/VCs cohort provided valuable information, future research is needed.
PMID- 29335061
TI - Estimating HIV Incidence Rates among MSM in an Urban Area of Chongqing Using
Three Approaches.
AB - To evaluate the HIV pandemic in Chongqing, the pooled PCR, IgG-capture BED enzyme
immunoassay (BED-CEIA), and cohort observations were used to estimate the HIV
incidences among men who have sex with men (MSM). 617 MSM subjects completed the
survey at a voluntary counseling and testing (VCT) site. The observed HIV
incidence was 12.5 per 100 P-Ys (95% CI = 9.1-15.7). The annual acute HIV
infection (AHI) incidence estimated by pooled PCR was 14.0% (95% CI = 10.9-17.1).
The HIV-1 annual incidence estimated based on the BED-CEIA was 12.0% (95% CI =
7.5-16.5). The HIV incidences estimated by these three approaches were consistent
and complementary. The HIV incidence rates were alarmingly high with an uptrend
among the urban MSM of Chongqing.
PMID- 29335062
TI - Epidemiology of Measles Cases in South Darfur State, Sudan, 2011-2015.
AB - Case-based surveillance measles data was defined according to World Health
Organization (WHO) guidelines. A total of 511 measles cases were studied from
2011 to 2015 in Southern Darfur State, Sudan and 58.1% of cases were confirmed
from Nyala city. About 43.4% of cases were males, 56.6% of cases were female, and
47.7% were children under five years old. Similarity, within February to June,
the cases increased by 8.0% in children vaccinated through measles campaign, and
5.3% in children that used child vaccination card and 78.7% in unvaccinated one.
The epidemiologically linked (EPI-Linked) measles cases declined from 2011 to
2015; consequently, Measles still remain to be a significant challenge in south
Darfur state, Sudan.
PMID- 29335063
TI - Tea Consumption is Associated with Increased Risk of Kidney Stones in Northern
Chinese: A Cross-sectional Study.
AB - Kidney stones are a common urinary system condition that can progress to kidney
disease. Previous studies on the association between tea consumption and kidney
stones are inconsistent. A cross-sectional study to investigate the association
between tea consumption and kidney stones was conducted from 2013 to 2014 and
recruited 9,078 northern Chinese adults. A total of 8,807 participants were
included in the final analysis. Participants' prevalence of kidney stones was
1.07%, 1.73%, and 2.25% based on their tea consumption frequency of never,
occasionally, and often groups, respectively. Compared with the 'never' group,
the odds ratios (95% confidence intervals) for the occurrence of kidney stones
were 1.57 (1.00-2.46) and 1.65 (1.06-2.57) in the 'occasionally' and 'often'
groups, respectively. After adjusting for sex, age, and other potential
confounding factors, tea consumption still significantly increased the risk of
kidney stones. Tea consumption is independently associated with an increased risk
of kidney stones in the investigated population, suggesting that a decrease in
the consumption of tea may be a preventive strategy for kidney stones.
PMID- 29335064
TI - Real-time Assessment of Cytosolic, Mitochondrial, and Nuclear Calcium Levels
Change in Rat Pheochromocytoma Cells during Pulsed Microwave Exposure Using a
Genetically Encoded Calcium Indicator.
AB - Little information is available about the effects of exposure to pulsed
microwaves on neuronal Ca2+ signaling under non-thermal conditions. In this
study, rat pheochromocytoma (PC12) cells were exposed to pulsed microwaves for 6
min at a specific absorption rate (SAR) of 4 W/kg to assess possible real-time
effects. During microwave exposure, free calcium dynamics in the cytosol,
mitochondria, and nucleus of cells were monitored by time-lapse microfluorimetry
using a genetically encoded calcium indicator (ratiometric-pericam, ratiometric
pericam-mt, and ratiometric-pericam-nu). We established a waveguide-based real
time microwave exposure system under accurately controlled environmental and
dosimetric conditions and found no significant changes in the cytosolic,
mitochondrial, or nuclear calcium levels in PC12 cells. These findings suggest
that no dynamic changes occurred in [Ca2+]c, [Ca2+]m, or [Ca2+]n of PC12 cells at
the non-thermal level.
PMID- 29335065
TI - Effects of Maternal Marginal Iodine Deficiency on Interactions between Cerebellar
Bergmann Glia Cells and Purkinje Cells in Rat Offspring.
AB - Iodine deficiency (ID) during early pregnancy has an adverse effect on children's
psychomotor and motor function but the mechanism has not been clarified.
Therefore, our aim was to study the effect of maternal marginal ID on cerebellar
neurodevelopment and the underlying mechanism. After obtaining marginal ID rats,
we examined interactions between Bergmann glia cells (BGs) and Purkinje cells
(PCs) using immunofluorescence and expression of the glutamate transporter and
receptor by western blot. Our results showed that marginal ID reduced the number
of contacted points between BGs and PCs, and disturbed expression of the
glutamate transporter and receptor. Our results support the hypothesis that
marginal ID inhibits interactions of BGs-PCs, which may be involved in abnormal
regulation of the glutamate transporter and receptor.
PMID- 29335066
TI - Up- and Down-regulated Leukemia-related Protein 16 Affects ERalpha Expression and
Prolactin Secretion by GH3 Cells.
AB - Prolactinoma is an estrogen-related tumor and leukemia-related protein 16 (LRP16)
is correlated with the progression of estrogen-related tumors, but the regulatory
mechanism between LRP16 and prolactinoma remain unclear. This study demonstrates
a variation in LRP16 with estrogen receptor alpha (ERalpha) in prolactinoma
models and the up and downregulation effects of LRP16 on prolactin secretion of
pituitary adenomas cells (GH3 cells). In our study, 50 male SD rats (30-day-old)
were randomly divided into five groups of 10 rats each. After 120 days of
treatment, the rats were sacrificed, and the expression of LRP16 and ERalpha were
examined by Western blot and immunohistochemistry to explore the changes in
ERalpha, LRP16, and prolactin. After siRNA transfection of the respective genes,
the GH3 cells were cultured, and their secretory function as well as the
expression of ERalpha mRNA and prolactin were analyzed by enzyme-linked
immunosorbent assay and real-time-polymerase chain reaction analysis. The results
show that secretion of prolactin by GH3 cells can be affected by up and
downregulating LRP16 expression, which may provide a novel medical therapy in
clinical trials.
PMID- 29335067
TI - Gata6 in pluripotent stem cells enhance the potential to differentiate into
cardiomyocytes.
AB - Pluripotent stem cell (PSC) variations can cause significant differences in the
efficiency of cardiac differentiation. This process is unpredictable, as there is
not an adequate indicator at the undifferentiated stage of the PSCs. We compared
global gene expression profiles of two PSCs showing significant differences in
cardiac differentiation potential. We identified 12 up-regulated genes related to
heart development, and we found that 4 genes interacted with multiple genes.
Among these genes, Gata6 is the only gene that was significantly induced at the
early stage of differentiation of PSCs to cardiomyocytes. Gata6 knock-down in
PSCs decreased the efficiency of cardiomyocyte production. In addition, we
analyzed 6 mESC lines and 3 iPSC lines and confirmed that a positive correlation
exists between Gata6 levels and efficiency of differentiation into
cardiomyocytes. In conclusion, Gata6 could be utilized as a biomarker to select
the best PSC lines to produce PSC-derived cardiomyocytes for therapeutic
purposes. [BMB Reports 2018; 51(2): 85-91].
PMID- 29335068
TI - Imprinted gene Zinc finger protein 127 is a novel regulator of master
pluripotency transcription factor, Oct4.
AB - Induced pluripotent stem cells (iPSCs) show great promise for replacing current
stem cell therapies in the field of regenerative medicine. However, the original
method for cellular reprogramming, involving four exogenous transcription
factors, is characterized by low efficiency. Here, we focused on using epigenetic
modifications to enhance the reprogramming efficiency. We hypothesized that there
would be a new reprogramming factor involved in DNA demethylation, acting on the
promoters of pluripotency-related genes. We screened proteins that bind to the
methylated promoter of Oct4 and identified Zinc finger protein 127 (Zfp127), the
functions of which have not yet been identified. We found that Zfp127 binds to
the Oct4 promoter. Overexpression of Zfp127 in fibroblasts induced demethylation
of the Oct4 promoter, thus enhancing Oct4 promoter activity and gene expression.
These results demonstrate that Zfp127 is a novel regulator of Oct4, and may
become a potent target to improve cellular reprogramming. [BMB Reports 2018;
51(5): 242-248].
PMID- 29335069
TI - Functional roles of glutamic acid E143 and E705 residues in the N-terminus and
transmembrane domain 7 of Anoctamin 1 in calcium and noxious heat sensing.
AB - Anoctamin 1 (ANO1) is an anion channel that is activated by changes in cytosolic
Ca2+ concentration and noxious heat. Although the critical roles of ANO1 have
been elucidated in various cell types, the control of its gating mechanisms by
Ca2+ and heat remain more elusive. To investigate critical amino acid residues
for modulation of Ca2+ and heat sensing, we constructed a randomized mutant
library for ANO1. Among 695 random mutants, reduced Ca2+ sensitivity was observed
in two mutants (mutant 84 and 87). Consequently, the E143A mutant showed reduced
sensitivity to Ca2+ but not to high temperatures, whereas the E705V mutant
exhibited reduced sensitivity to both Ca2+ and noxious heat. These results
suggest that the glutamic acids (E) at 143 and 705 residues in ANO1 are critical
for modulation of Ca2+ and/or heat responses. Furthermore, these findings help to
provide a better understanding of the Ca2+-mediated activation and heat-sensing
mechanism of ANO1. [BMB Reports 2018; 51(5): 236-241].
PMID- 29335070
TI - Cell proliferation and migration mechanism of caffeoylserotonin and serotonin via
serotonin 2B receptor in human keratinocyte HaCaT cells.
AB - Caffeoylserotonin (CaS), one derivative of serotonin (5-HT), is a secondary
metabolite produced in pepper fruits with strong antioxidant activities. In this
study, we investigated the effect of CaS on proliferation and migration of human
keratinocyte HaCaT cells compared to that of 5-HT. CaS enhanced keratinocyte
proliferation even under serum deficient condition. This effect of CaS was
mediated by serotonin 2B receptor (5-HT2BR) related to the cell proliferation
effect of 5-HT. We also confirmed that both CaS and 5-HT induced G1 progression
via 5-HT2BR/ERK pathway in HaCaT cells. However, Akt pathway was additionally
involved in upregulated expression levels of cyclin D1 and cyclin E induced by
CaS by activating 5-HT2BR. Moreover, CaS and 5-HT induced cell migration in HaCaT
cells via 5-HT2BR. However, 5-HT regulated cell migration only through ERK/AP
1/MMP9 pathway while additional Akt/NF-kappaB/MMP9 pathway was involved in the
cell migration effect of CaS. These results suggest that CaS can enhance
keratinocyte proliferation and migration. It might have potential as a reagent
beneficial for wound closing and cell regeneration. [BMB Reports 2018; 51(4): 188
193].
PMID- 29335072
TI - Rebound excitability mediates motor abnormalities in Parkinson's disease.
AB - Parkinson's disease (PD) is a debilitating disorder resulting from loss of
dopamine neurons. In dopamine deficient state, the basal ganglia increases
inhibitory synaptic outputs to the thalamus. This increased inhibition by the
basal ganglia output is known to reduce firing rate of thalamic neurons that
relay motor signals to the motor cortex. This 'rate model' suggests that the
reduced excitability of thalamic neurons is the key for inducing motor
abnormalities in PD patients. We reveal that in response to inhibition, thalamic
neurons generate rebound firing at the end of inhibition. This rebound firing
increases motor cortical activity and induces muscular responses that triggers
Parkinsonian motor dysfunction. Genetic and optogenetic intervention of the
rebound firing prevent motor dysfunction in a mouse model of PD. Our results
suggest that inhibitory synaptic mechanism mediates motor dysfunction by
generating rebound excitability in the thalamocortical pathway. [BMB Reports
2018; 51(1): 3-4].
PMID- 29335071
TI - Adequate concentration of B cell leukemia/lymphoma 3 (Bcl3) is required for
pluripotency and self-renewal of mouse embryonic stem cells via downregulation of
Nanog transcription.
AB - B cell leukemia/lymphoma 3 (Bcl3) plays a pivotal role in immune homeostasis,
cellular proliferation, and cell survival, as a co-activator or co-repressor of
transcription of the NF-kappaB family. Recently, it was reported that Bcl3
positively regulates pluripotency genes, including Oct4, in mouse embryonic stem
cells (mESCs). However, the role of Bcl3 in the maintenance of pluripotency and
self-renewal activity is not fully established. Here, we report the dynamic
regulation of the proliferation, pluripotency, and self-renewal of mESCs by Bcl3
via an influence on Nanog transcriptional activity. Bcl3 expression is
predominantly observed in immature mESCs, but significantly decreased during cell
differentiation by LIF depletion and in mESC-derived EBs. Importantly, the
knockdown of Bcl3 resulted in the loss of self-renewal ability and decreased cell
proliferation. Similarly, the ectopic expression of Bcl3 also resulted in a
significant reduction of proliferation, and the self-renewal of mESCs was
demonstrated by alkaline phosphatase staining and clonogenic single cell-derived
colony assay. We further examined that Bcl3-mediated regulation of Nanog
transcriptional activity in mESCs, which indicated that Bcl3 acts as a
transcriptional repressor of Nanog expression in mESCs. In conclusion, we
demonstrated that a sufficient concentration of Bcl3 in mESCs plays a critical
role in the maintenance of pluripotency and the self-renewal of mESCs via the
regulation of Nanog transcriptional activity. [BMB Reports 2018; 51(2): 92-97].
PMID- 29335073
TI - [Enhance research, prevention and control of pertussis for protecting public
confidence in vaccination: focus on the adverse events of vaccine with
insufficient potency and its long-term impacts].
AB - On November 3, 2017, the China Food and Drug Administration reported that the
potency indexes of two batches of diphtheria-pertussis-tetanus vaccines produced
by two companies did not reach the requirements. Insufficient potency could
affect the protection effect of these vaccines immunization. Currently, pertussis
cases have already showed an increasing trend in China and could last for several
years. Such an increase could be linked to these adverse events of vaccine with
insufficient potency, which could become an evidence to challenge or deny the
effectiveness of vaccination, and brings a persistent inhibition of the public's
acceptance for vaccination. The wider global context of pertussis resurgence,
previous underestimate on the domestic pertussis, the promotion of detection
methods, the change of knowledge about pertussis, the confirmation of pertussis
in elder children and adults, the antigenicity variation of pertussis strains
could lead to a significant increase of pertussis cases. Health researchers and
clinical workers should raise awareness about these factors, and assess
rationally the impact of vaccine titer deficiency on pertussis epidemiology for
maintaining and promoting public confidence in vaccination.
PMID- 29335074
TI - Trends in narcotics and sedative use during mechanical ventilation of preterm
infants in Canadian neonatal intensive care units.
AB - OBJECTIVE: Mechanical ventilation (MV) in preterm infants (PTI) causes
discomfort. Whether it causes pain is controversial. Meta analysis reviews of
published work on PTI during MV have shown no clinically significant impact of
opioids on pain scales, and hence not recommended for routine use in neonatal
intensive care units (NICUs). Similarly regular use of sedative midazolam is also
not recommended. Therefore we hypothesized a downward trend in narcotics and
sedatives used in MV of PTI in NICUs. This study aimed to assess trends of
sedatives and narcotics use during MV of PTI in Canadian NICUs during 2004-2009.
METHODS: PTI born at gestational age (GA) of <35 weeks requiring invasive MV for
>24 hours were identified retrospectively from the Canadian Neonatal Network
database for 2004-2009. PTI were excluded if moribund on admission, had major
congenital anomalies, surgery (except laser eye surgery), necrotizing
enterocolitis, chest tube or history of maternal narcotic abuse. PTI were
classified according to whether they received any narcotics (morphine, fentanyl,
methadone, sufentanyl, meperidine, alfentynl and codiene) or sedatives (chloral
hydrate, midazolam, lorazepam, phenobarbital, pentobarbital, ketamine and
propofol) for >24 consecutive hours during MV. Trends of narcotics and sedatives
were assessed using the Cochrane-Armitage Trend test separately for PTI born at
<29 and 29-34 weeks of GA. RESULTS: Among 5 638 study subjects, 2 169 (38.5%)
received narcotics and 897 (15.9%) received sedatives. The most common narcotics
were morphine (62.2%) and fentanyl (63.8%) and sedatives were phenobarbital
(44.9%) and chloral hydrate (44.2%). A significant decreasing trend (P<0.01) in
the use of any sedatives during MV was observed in PTI <29 and 29-34 weeks of GA.
However, the use of any narcotics during MV increased significantly (P=0.03)
among PTI <29 weeks of GA, and no change in trend was detected for PTI born at 29
34 weeks of GA. CONCLUSIONS: The use of sedatives during MV in PTI born at <35
weeks of GA was positively affected, however the narcotics use during MV remained
constant for PTI born at 29-34 weeks, and increased in extremely low GA group
(less than 29 weeks) suggesting evidence based practice change was not observed
during the study period.
PMID- 29335075
TI - [A study of Ververck index in 16 865 singleton neonates with a gestational age of
27-42 weeks in Shenzhen, China].
AB - OBJECTIVE: Ververck index (VI) reflects thoracic development, body type, and
nutritional status. This study aimed to investigate the VI of singleton neonates
with a gestational age (GA) of 27-42 weeks at birth, and to establish percentile
curves of VI of the neonates. METHODS: Cross-sectional cluster sampling was
performed between April 2013 and September 2015. Body weight, body length, and
chest circumference were measured for 16 865 singleton neonates with a GA of 27
42 weeks in two hospitals in Shenzhen, China. VI was calculated and the
percentile curves of VI were plotted for the neonates. RESULTS: Mean VIs were
obtained for singleton neonates with a gestational age of 27-42 weeks (in three
groups of male, female, and both sexes), and related 3rd-97th percentile curves
were plotted. As for the 50th percentile curve, the singleton neonates with a GA
of 27 weeks had the lowest 50th percentile value of VI, which gradually increased
with the increase in GA. The singleton neonates with a GA of 42 weeks had the
highest 50th percentile value of VI. Girls had a slightly higher 50th percentile
value of VI than boys in all GA groups. CONCLUSIONS: VI of neonates increases
with the increase in GA. Female neonates may have a slightly better thoracic
development, body type, and nutritional status than male neonates at birth. The
percentile curves of VI plotted for singleton neonates with a GA of 27-42 weeks
(in three groups of male, female, and both sexes) can provide a basis for
evaluating thoracic development, body type, and nutritional status of neonates at
birth in Shenzhen, China.
PMID- 29335076
TI - [Value of arterial blood lactic acid in the evaluation of disease severity and
prognosis in neonatal shock].
AB - OBJECTIVE: To evaluate the value of blood lactic acid (BLA) as a predictor for
the severity and prognosis of neonatal shock. METHODS: A total of 326 neonates
with shock were enrolled and divided into three groups based on the severity,
namely mild group (n=147), moderate group (n=105), and severe group (n=74). BLA
level was measured during and early after (about 6 hours later) fluid
resuscitation, and lactate clearance rate (LCR) was calculated. The receiver
operating characteristic (ROC) curve was applied to evaluate the predictive value
of BLA in neonatal shock. RESULTS: BLA level was high in all subjects prior to
treatment, and was highest in the severe group and lowest in the mild group
(P<0.01). BLA level was significantly higher among patients with septic shock
than among those with hypovolemic, cardiogenic, and asphyxiating shock (P<0.05).
BLA level was significantly reduced in patients in recovery after treatment
(P<0.05). Mortality was significantly lower in patients with BLA level <=4 mmol/L
or LCR >=10% than in those with BLA level >4 mmol/L or LCR <10% (P<0.01). BLA at
11.15 mmol/L had 100% sensitivity and 96.8% specificity in predicting severe
shock. BLA at 10.65 mmol/L had 88.9% sensitivity and 74.1% specificity in
predicting the prognosis (survival or dead) of newborns with shock. CONCLUSIONS:
In neonates with shock, arterial BLA level increases as the disease severity
increases and is associated with prognosis, so it is a useful predictor of the
severity and prognosis of neonatal shock.
PMID- 29335077
TI - [Burden of pediatric cancer in Jiangxi, China, in 2010 and 2015].
AB - OBJECTIVE: To study the burden of pediatric cancer in Jiangxi, China, in 2010 and
2015 and its changes from 2010 to 2015. METHODS: The data of pediatric cancer in
Jiangxi in 2010 and 2015 were collected from the Global Burden of Disease Study
2015 in China, including number of cases, number of deaths, years of life lost
(YLL), years lived with disability (YLD), and disability-adjusted life years
(DALY). The standardized incidence rate, mortality rate, and DALY rate were
calculated with the national census data in 2010 as the standard population, in
order to evaluate the changes in incidence, mortality, and disease burden of
pediatric cancer in Jiangxi. RESULTS: In both 2010 and 2015, boys had higher
numbers of cases, deaths, and DALY than girls, and the 5-14 years group had
higher numbers than the 0-4 years group; boys had higher incidence rate,
mortality rate, and DALY rate than girls, and the 0-4 years group had higher
rates than the 5-14 years group. In 2015, the standardized incidence rate of
pediatric cancer was reduced by 6.66% in the 0-4 years group and 17.56% in the 5
14 years group; the standardized mortality rate was reduced by 11.34% in the 0-4
years group and 21.78% in the 5-14 years group; the standardized DALY rate was
reduced by 11.27% in the 0-4 years group and 21.67% in the 5-14 years group.
Among the different types of pediatric cancer, leukemia had the highest
standardized DALY rate in 2010 and 2015, followed by brain cancer and non
Hodgkin's lymphoma. CONCLUSIONS: There was a certain reduction in the burden of
pediatric cancer in Jiangxi from 2010 to 2015. Leukemia, brain cancer, and non
Hodgkin's lymphoma are the focus of prevention and treatment, and children aged
less than 5 years and boys should be closely monitored.
PMID- 29335078
TI - [Value of indoleamine 2,3-dioxygenase in diagnosis of systemic inflammatory
response syndrome after cardiopulmonary bypass in children with congenital heart
disease].
AB - OBJECTIVE: To study the value of indoleamine 2,3-dioxygenase (IDO) in the early
diagnosis of systemic inflammatory response syndrome (SIRS) after cardiopulmonary
bypass in children with congenital heart disease. METHODS: A total of 90 children
with congenital heart disease who underwent cardiopumonary bypass surgery between
May 2012 and January 2016 were enrolled. According to the prsence or absence of
SIRS after surgery, they were divided into SIRS group (n=43) and control group
(n=47). Peripheral blood samples were collected before surgery, during surgery,
and after surgery. Serum levels of IDO, C-reactive protein (CRP), and interleukin
6 (IL-6) were measured and compared between the two groups. The receiver
operating characteristic (ROC) curve was used to evaluate their diagnostic
efficiency. RESULTS: Compared with the control group, the SIRS group had higher
serum CRP levels at 72 hours after surgery, higher IL-6 levels during surgery and
at 72 hours after surgery, and higher IDO levels at 24 and 72 hours after
surgery. IDO had a certain value in the diagnosis of SIRS at 24 hours after
surgery with an area under the ROC curve (AUC) of 0.793, a specificity of 100%,
and a sensitivity of 58.14%. CRP, IL-6, and IDO had a certain value in the
diagnosis of SIRS at 72 hours after surgery. IDO had the highest diagnostic
efficiency with an AUC of 0.927, a specificity of 95.74%, and a sensitivity of
76.74% at 72 hours after surgery. CONCLUSIONS: IL-6, CRP, and IDO have a certain
value in the diagnosis of SIRS after surgery for congenital heart disease, and
IDO has a higher diagnostic efficiency. IDO can predict the development of SIRS
in children after surgery for congenital heart disease earlier.
PMID- 29335079
TI - [Expression of plasma miRNA-497 in children with sepsis-induced myocardial injury
and its clinical significance].
AB - OBJECTIVE: To study the expression of plasma miRNA-497 in children with sepsis
induced myocardial injury and its clinical significance. METHODS: A total of 148
children with sepsis were enrolled. According to the presence or absence of
myocardial injury, these children were divided into myocardial injury group
(n=58) and non-myocardial injury group (n=90). The two groups were compared in
terms of the changes in plasma levels of miRNA-497, cardiac troponin I (cTnI),
creatine kinase-MB (CK-MB), N-terminal pro-brain natriuretic peptide (NT-proBNP),
procalcitonin (PCT), and C-reactive protein (CRP) and left ventricular ejection
fraction (LVEF). The receiver operating characteristic (ROC) curve was plotted to
evaluate the value of plasma miRNA-497, cTnI, and CK-MB in the diagnosis of
myocardial injury. A Pearson correlation analysis was used to determine the
correlation of miRNA-497 with cTnI, CK-MB, NT-proBNP, PCT, CRP, and LVEF.
RESULTS: Compared with the non-myocardial injury group, the myocardial injury
group had significantly higher plasma levels of miRNA-497, cTnI, CK-MB, NT
proBNP, PCT, and CRP (P<0.05). Plasma miRNA-497, cTnI, and CK-MB when measured
alone or in combination had an area under the ROC curve of 0.918, 0.931, 0.775,
and 0.940 respectively. At the optimal cut-off value of 2.05, miRNA-497 had a
sensitivity of 90.4% and a specificity of 91.2%. The correlation analysis showed
that there was a good correlation between plasma miRNA-497 and cTnI in children
with myocardial injury (r=0.728, P<0.01). CONCLUSIONS: Plasma miRNA-497 has a
similar value as cTnI in the diagnosis of sepsis-induced myocardial injury in
children and may be used as a potential marker for early diagnosis of myocardial
injury.
PMID- 29335080
TI - [Clinical characteristics of refractory Mycoplasma pneumoniae pneumonia in
children].
AB - OBJECTIVE: To provide a basis for early diagnosis and treatment of refractory
Mycoplasma pneumoniae pneumonia (RMPP) in children by comparing the clinical
characteristics of RMPP and general Mycoplasma pneumoniae pneumonia (MPP).
METHODS: Children with MPP hospitalized between October 2015 and December 2016
were selected as study subjects. According to the diagnostic criteria, children
were divided into RMPP group (n=152) and MPP group (n=551). The differences
between the two groups in the basic situation, clinical manifestations, infection
parameters and myocardial enzymes were compared. RESULTS: There were no
significant differences in gender and age between the RMPP and MPP groups
(P>0.05). The peak temperature in the RMPP group was significantly higher than
that in the MPP group on the first day of admission (P<0.01). The percentage of
children with augmentation in the RMPP group was lower than that in the MPP group
(P=0.009). The percentage of neutrophils [Ne(%)] and serum procalcitonin (PCT)
levels in the RMPP group were both higher than those in the MPP group (P<0.05),
while the percentage of lymphocytes was significantly lower in the RMPP group
(P<0.05). The serum levels of aspartate aminotransferase (AST) and lactate
dehydrogenase (LDH) in the RMPP group were also higher than those in the MPP
group (P<0.05). Binary logistic regression analysis showed that the peak
temperature and LDH were closely related to RMPP in children (P<0.05). Receiver
operating characteristic (ROC) curve analysis showed that the area under the
curve (AUC) of the peak temperature and LDH for the diagnosis of RMPP was 0.647
and 0.637 respectively. In children <=2 years old, when the threshold value of
LDH was 400 U/L, the diagnostic sensitivity was 52.63% and the specificity was
54.84%. In children above 2 years old, when the threshold value of LDH was 335
U/L, the diagnostic sensitivity was 69.92% and the specificity was 51.55%.
CONCLUSIONS: The children with RMPP have a high fever in the early stage.
Meanwhile there are abnormal laboratory test results in these children. Elevated
serum LDH levels have a high clinical value of early diagnosis of RMPP,
especially in children above 2 years.
PMID- 29335081
TI - [Expression of vascular intercellular adhesion molecule-1 and its significance in
children with bronchiolitis].
AB - OBJECTIVE: To investigate the expression of intercellular adhesion molecule-1
(ICAM-1) in serum and induced sputum supernatant in children with bronchiolitis,
as well as its role in the pathogenesis of bronchiolitis in children. METHODS: A
total of 67 children with bronchiolitis who were diagnosed and hospitalized
between July 2015 and January 2017 were enrolled. According to the diagnostic
criteria, these children were divided into mild group with 22 children, moderate
group with 24 children, and severe group with 21 children. A total of 20 children
who underwent physical examination were enrolled as healthy control group. ELISA
was used to measure the level of ICAM-1 in serum and induced sputum supernatant
in the children with bronchiolitis in the acute stage and recovery stage and the
children in the healthy control group. RESULTS: Compared with the healthy control
group, the mild, moderate, and severe bronchiolitis groups had a significant
increase in the level of ICAM-1 in serum and sputum (P<0.01). Compared with the
mild group, the moderate and severe groups had a significant increase in the
level of ICAM-1 in serum and sputum (P<0.01). Compared with the moderate group,
the severe group had a significant increase in the level of ICAM-1 in serum and
sputum (P<0.01). Compared with the children with bronchiolitis in the acute
stage, the children in the recovery stage had a significant reduction in the
level of ICAM-1 in serum and sputum (P<0.01). The correlation analysis showed
that in the acute stage, the level of ICAM-1 in serum was positively correlated
with that in sputum in children with bronchiolitis (r=0.875, P<0.001).
CONCLUSIONS: ICAM-1 is involved in the pathogenesis of bronchiolitis and is
associated with disease severity.
PMID- 29335082
TI - [A comparative analysis of anti-N-methyl-D-aspartate receptor encephalitis with
or without abnormal findings on cranial magnetic resonance imaging].
AB - OBJECTIVE: To investigate the clinical features of children with anti-N-methyl-D
aspartate receptor (anti-NMDAR) encephalitis with normal or abnormal cranial
magnetic resonance imaging (MRI) findings via a comparative analysis. METHODS: A
retrospective analysis was performed for the clinical data of 33 children with
anti-NMDAR encephalitis. The clinical features and prognosis were compared
between the children with normal and abnormal cranial MRI findings. RESULTS: In
the 33 children with anti-NMDAR encephalitis, the most common initial symptoms
were seizures (61%) and involuntary movement (61%), followed by language disorder
(54%), mental and behavioral abnormalities (52%), and disturbance of
consciousness (30%). All children had positive anti-NMDAR antibody in the
cerebrospinal fluid, and 29 children (88%) had positive serum antibody. Of all
the children, 15 (46%) had increased leukocytes in the cerebrospinal fluid, 3
(9%) had an increase in protein, and 29 (88%) had positive oligoclonal band; 26
children (79%) had electroencephalographic abnormalities (epileptic wave, slow
wave, or a combination of these two types of waves). One child experienced
respiratory failure. One child was found to have germinoma in the sellar region
during follow-up. Of all the 33 children, 13 (39%) had abnormal cranial MRI
findings, with hypointensity or isointensity on T1W1 and hyperintensity on T2WI
and T2-FLAIR; 2 children had dural enhancement. As for the location of lesion, 5
children (38%) had lesions in the temporal lobe, 3 (23%) in the frontal lobe, 3
(23%) in the basal ganglia, 2 (15%) in the parietal lobe, 2 (15%) in the
occipital lobe, 2 (15%) in the brainstem, 1 (8%) in the thalamus, and 1 (8%) in
the cerebellum. Among the 13 children with abnormal cranial MRI findings, 5 (38%)
had lesions mainly in the grey matter and 8 (62%) had lesions mainly in the white
matter. Compared with the children with normal cranial MRI findings, the children
with abnormal cranial MRI findings had significantly higher proportion of
children with prodromal infection, incidence rate of disturbance of
consciousness, probability of recurrence, Glasgow score, incidence rate of
increased leukocytes in the cerebrospinal fluid, and application rate of second
line treatment (P<0.05). CONCLUSIONS: Children with anti-NMDAR encephalitis and
abnormal cranial MRI findings have certain clinical features, which may provide
guidance for the evaluation of disease conditions and the selection of diagnostic
and treatment measures.
PMID- 29335083
TI - [Clinical and cytogenetic study in a child with de novo chromosome 9
abnormality].
AB - This study aimed to analyze the clinical phenotype of chromosome 9p deletion or
duplication and its relationship with karyotype. A patient, female, aged 6
months, visited the hospital due to motor developmental delay. Karyotype analysis
identified abnormalities of chromosome 9 short arm, and high-throughput
sequencing found 9p24.3-9p23 deletion and 9p23-9p13.1 duplication. Her parents
had a normal karyotype. Karyotype analysis combined with high-throughput
sequencing is of great significance for improving the efficiency of etiological
diagnosis in children with motor developmental delay or multiple congenital
deformities and mental retardation.
PMID- 29335084
TI - [Influence of cow's milk protein allergy on the diagnosis of functional
gastrointestinal diseases based on the Rome IV standard in infants and young
children].
AB - OBJECTIVE: To study the influence of cow's milk protein allergy (CMPA) on the
diagnosis of functional gastrointestinal diseases (FGID) based on the Rome IV
standard in infants and young children. METHODS: A total of 84 children aged 1
month to 3 years who were diagnosed with CMPA were enrolled as the case group,
and 84 infants and young children who underwent physical examination and had no
CMPA were enrolled as the control group. The pediatricians specializing in
gastroenterology asked parents using a questionnaire for the diagnosis of FGID
based on the Rome IV standard to assess clinical symptoms and to diagnose FGID.
RESULTS: The case group had a significantly higher incidence rate of a family
history of allergies than the control group (P<0.05). In the case group, 38 (45%)
met the Rome IV standard for the diagnosis of FGID, while in the control group,
13 (15%) met this standard (P<0.05). According to the Rome IV standard for FGID,
the case group had significantly higher diagnostic rates of reflex, functional
diarrhea, difficult defecation, and functional constipation than the control
group (P<0.05). The children who were diagnosed with FIGD in the control group
were given conventional treatment, and those in the case group were asked to
avoid the intake of cow's milk protein in addition to the conventional treatment.
After 3 months of treatment, the case group had a significantly higher response
rate to the treatment than the control group (P<0.05). CONCLUSIONS: In infants
and young children, CMPA has great influence on the diagnosis of FGID based on
the Rome IV standard. The possibility of CMPA should be considered during the
diagnosis of FGID.
PMID- 29335085
TI - [Impact of transition readiness on quality of life in children with chronic
diseases].
AB - OBJECTIVE: To investigate the current quality of life in children with chronic
diseases, and to explore the impact of transition readiness on quality of life.
METHODS: A total of 332 children with chronic diseases from two children's
hospitals in Shanghai, China were enrolled. A self-designed demographic
questionnaire, Pediatric Quality of Life Inventory 4.0 Generic Core Scales
(PedsQLTM 4.0), and Self-Management and Transition to Adulthood with Rx=Treatment
(STARx) Questionnaire were used to evaluate transition readiness and quality of
life. RESULTS: The children with chronic diseases had a significantly lower total
quality of life score than the national norm (74.66+/-15.85 vs 81.81+/-12.03;
P<0.001). Doctor-patient communication and health care responsibilities (the
child's abilities to take care of himself/herself and adaptation to the process
of diagnosis and treatment from childhood to adulthood) were positively
correlated with the scores on each dimension of quality of life (P<0.05).
Duration of disease, time of absence from school within six months, and the
number of types of drugs taken orally were negatively correlated with the total
quality of life score (rs=-0.172, -0.236, and -0.280; P<0.05). The residence
(urban or rural area), monthly family income, parents' educational level, and
father's occupation had significant influence on children's quality of life
(P<0.05). The hierarchical multiple regression analysis revealed that doctor
patient communication and health care responsibilities led to a 14.3% increase in
the explanation of the total variation in quality of life (P<0.001). CONCLUSIONS:
Quality of life is not satisfactory in children with chronic diseases. Two
domains of transition readiness, namely the abilities to communicate with health
providers and health care responsibilities, are major factors influencing quality
of life in these children.
PMID- 29335086
TI - [Research progress in drug therapy for bronchopulmonary dysplasia in preterm
infants].
AB - Bronchopulmonary dysplasia (BPD) is the most common long-term complication in
surviving extremely preterm infants. This may lead to pulmonary hypertension,
increase late neonatal mortality, and cause abnormal neural development. There is
still controversy over the efficacy, as well as advantages and disadvantages, of
drug therapy for BPD in preterm infants. This article reviews the research
progress in the drug therapy for BPD.
PMID- 29335087
TI - [Research advances in the association between transient receptor potential cation
channel 6 and kidney disease].
AB - Transient receptor potential cation channel 6 (TRPC6) is a member of the
transient receptor superfamily encoded by the TRPC6 gene and is widely expressed
in tissues and organs of the human body, especially in the glomerular podocytes.
TRPC6 interacts with various slit diaphragm (SD) proteins including podocin,
nephrin, ACTN4, and CD2AP to maintain the normal structure and function of
glomerular podocytes. Foot process fusion caused by podocyte damage due to
various factors is the most important morphological change in kidney disease.
This article reviews the biological function of TRPC6 and its effect on kidney
disease.
PMID- 29335088
TI - [Role of programmed death-1 in viral infectious diseases].
AB - The research on the immunoregulatory effect of programmed death-1 (PD-1) in
infectious diseases mainly focuses on chronic viral infection, but there are few
studies on acute viral infection. In chronic viral infection, PD-1 is highly
expressed on the surface of CD8+ T cells, which is a sign of CD8+ T cell
depletion. Recent studies have shown that in chronic viral infection, PD-1 is
also highly expressed on the surface of regulatory T cells and binds to
programmed death-ligand 1 (PD-L1) on the surface of exhausted CD8+ T cells,
resulting in a stronger inhibitory effect on CD8+ T cell immunity. Blocking the
PD-1/PD-L1 signaling pathway between exhausted CD8+ T cells and regulatory T
cells can significantly reverse the depletion of CD8+ T cells and greatly improve
the antiviral effect of CD8+ T cells. However, the role of the PD-1/PD-L1
signaling pathway in acute viral infection remains unknown. This article
summarizes the latest research on PD-1 in infectious diseases and discusses its
role in acute and chronic viral infection.
PMID- 29335089
TI - Associations between clinical indicators of quality and aged-care residents.
AB - Objectives To ascertain Australian multistate prevalence and incidence of five
commonly collected clinical indicators of aged-care home quality and to measure
associations between these clinical indicators and levels of care needs and
consumer and staff satisfaction.Methods A retrospective analysis of national
audit data collected from 426 facilities between 2015 and 2016 was performed.
Regression models were used to examine associations between five clinical
indicators (falls, pressure injury, physical restraint, unplanned weight loss and
polypharmacy) and level of care needs measured by the Aged Care Funding
Instrument (ACFI) and consumer and care staff survey responses.Results With the
exception of polypharmacy, commonly collected negative clinical outcomes were
rare events. Compared with care homes with <25% of residents having high-level
care needs (high ACFI), homes with 25<75% high-ACFI residents had more
occurrences of all negative clinical outcomes except pressure injury. Homes with
>=75% high-ACFI residents reported the highest rates of polypharmacy (odds ratio
1.48, 95% confidence interval 1.39 - 1.57). Falls, unplanned weight loss and
pressure injury were inversely associated with satisfaction scores adjusted for
residents' level of care needs.Conclusions This first Australian study of
multistate clinical indicator data suggests interpretation of clinical indicators
of aged-care home quality requires consideration of the level of residents' care
needs.What is known about the topic? Many Australian aged-care providers use
quality indicators (QI) through benchmarking companies or in-house programs. The
five most widely used aged-care clinical QIs in Australia are falls, pressure
injury, physical restraint, unplanned weight loss and polypharmacy. Prevalence
and incidence of these QIs are highly variable among Australian studies. A
consistent message in the international literature is that residents' clinical
characteristics influence QI outcomes at baseline and may continue to influence
outcomes over time. Study of associations between Australian aged-care home
characteristics and QI outcomes has been limited.What does this paper add? This
is the first Australian study of multistate clinical QI data. It is also the
first to consider the level of resident care needs in the interpretation of
clinical QI outcomes and exploration of the association between level of consumer
and staff satisfaction and QI outcomes.What are the implications for
practitioners? Understanding the connections between aged-care home
characteristics, consumer and staff perceptions and clinical QIs is crucial in
the meaningful interpretation of QI outcomes in context. With the recent
introduction of the National Aged Care Quality Indicator Program, it is timely to
review national policy, to gauge current quality of care and the measure of care
quality in the sector, and to develop directions for possible research to inform
and resolve debates regarding the potential influence and unplanned effects that
such a program may have.
PMID- 29335090
TI - Improving the efficacy of healthcare services for Aboriginal Australians.
AB - Objective The aim of the present systematic review was to examine the enablers
for effective health service delivery for Aboriginal Australians.Methods This
systematic review was undertaken in accordance with the Preferred Reporting Items
for Systematic Reviews and Meta-Analyses (PRISMA) statement. Papers were included
if they had data related to health services for Australian Aboriginal people and
were published between 2000 and 2015. The 21 papers that met the inclusion
criteria were assessed using the Effective Public Health Practice Project Quality
Assessment Tool for Quantitative Studies. Seven papers were subsequently excluded
due to weak methodological approaches.Results There were two findings in the
present study: (1) that Aboriginal people fare worse than non-Aboriginal people
when accessing usual healthcare services; and (2) there are five enablers for
effective health care services for Australian Aboriginal people: cultural
competence, participation rates, organisational, clinical governance and
compliance, and availability of services.Conclusions Health services for
Australian Aboriginal people must be tailored and implementation of the five
enablers is likely to affect the effectiveness of health services for Aboriginal
people. The findings of the present study have significant implications in
directing the future design, funding, delivery and evaluation of health care
services for Aboriginal Australians.What is known about the topic? There is
significant evidence about poor health outcomes and the 10-year gap in life
expectancy between Aboriginal and non-Aboriginal people, and limited evidence
about improving health service efficacy.What does this paper add? This systematic
review found that with usual health care delivery, Aboriginal people experience
worse health outcomes. This paper identifies five strategies in the literature
that improve the effectiveness of health care services intended for Aboriginal
people.What are the implications for practitioners? Aboriginal people fare worse
in both experience and outcomes when they access usual care services. Health
services intended for Aboriginal people should be tailored using the five
enablers to provide timely, culturally safe and high-quality care.
PMID- 29335091
TI - Repositioning interprofessional education from the margins to the centre of
Australian health professional education ? what is required?
AB - Objective This paper examines the implementation and implications of four
development and research initiatives, collectively titled the Curriculum Renewal
Studies program (CRS), occurring over a 6-year period ending in 2015 and focusing
on interprofessional education (IPE) within Australian pre-registration health
professional education.Methods The CRS was developed as an action-focused and
participatory program of studies. This research and development program used a
mixed-methods approach. Structured survey, interviews and extensive documentary
analyses were supplemented by semi-structured interviews, focus groups, large
group consultations and consensus building methods. Narrative accounts of
participants' experiences and an approach to the future development of Australian
IPE were developed.Results Detailed accounts of existing Australian IPE curricula
and educational activity were developed. These accounts were published and used
in several settings to support curriculum and national workforce development.
Reflective activities engaging with the findings facilitated the development of a
national approach to the future development of Australian IPE - a national
approach focused on coordinated and collective governance and
development.Conclusion This paper outlines the design of an innovative approach
to national IPE governance and development. It explores how ideas drawn from
sociocultural theories were used to guide the choice of methods and to enrich
data analysis. Finally, the paper reflects on the implications of CRS findings
for health professional education, workforce development and the future of
Australian IPE.What is known about the topic? IPE to enable the achievement of
interprofessional and collaborative practice capabilities is widely accepted and
promoted. However, many problems exist in embedding and sustaining IPE as a
system-wide element of health professional education. How these implementation
problems can be successfully addressed is a health service and education
development priority.What does this paper add? The paper presents a summary of
how Australian IPE was conceptualised, developed and delivered across 26
universities during the period of the four CRS studies. It points to strengths
and limitations of existing IPE. An innovative approach to the future development
of Australian IPE is presented. The importance of sociocultural factors in the
development of practitioner identity and practice development is identified.What
are the implications for practitioners? The findings of the CRS program present a
challenging view of current Australian IPE activity and what will be required to
meet industry and health workforce expectations related to the development of an
Australian interprofessional- and collaborative-practice-capable workforce.
Although the directions identified pose considerable challenges for the higher
education and health sectors, they also provide a consensus-based approach to the
future development of Australian IPE. As such they can be used as a blueprint for
national development.
PMID- 29335092
TI - The Journal of Cataract & Refractive Surgery: New look, new year.
PMID- 29335093
TI - Changes in biomechanically corrected intraocular pressure and dynamic corneal
response parameters before and after transepithelial photorefractive keratectomy
and femtosecond laser-assisted laser in situ keratomileusis.
AB - PURPOSE: To evaluate the changes in biomechanically corrected intraocular
pressure (IOP) and new dynamic corneal response parameters measured by a dynamic
Scheimpflug analyzer before and after transepithelial photorefractive keratectomy
(PRK) and femtosecond laser-assisted laser in situ keratomileusis (LASIK).
SETTING: Yonsei University College of Medicine and Eyereum Eye Clinic, Seoul,
South Korea. DESIGN: Retrospective case series. METHODS: Medical records of
patients having transepithelial PRK or femtosecond-assisted LASIK were examined.
The primary outcome variables were biomechanically corrected IOP and dynamic
corneal response parameters, including deformation amplitude ratio 2.0 mm,
stiffness parameter at first applanation, Ambrosio relational thickness through
the horizontal meridian, and integrated inverse radius before the procedure and 6
months postoperatively. RESULTS: Of the 129 patients (129 eyes) in the study, 65
had transepithelial PRK and 64 had femtosecond-assisted LASIK. No significant
differences in biomechanically corrected IOP were noted before and after surgery.
The deformation amplitude ratio 2.0 mm and integrated inverse radius increased,
whereas the stiffness parameter at first applanation and the Ambrosio relational
thickness through the horizontal meridian decreased after surgery (P < .001). The
changes in deformation amplitude ratio 2.0 mm and integrated inverse radius were
smaller in transepithelial PRK than femtosecond-assisted LASIK (P < .001). Using
analysis of covariance, with refractive error change or corneal thickness change
as a covariate, the changes in deformation amplitude ratio 2.0 mm and integrated
inverse radius were smaller in transepithelial PRK than femtosecond-assisted
LASIK (P < .001). CONCLUSIONS: The dynamic Scheimpflug analyzer showed stable
biomechanically corrected IOP measurement before and after surgery. The changes
in dynamic corneal response parameters were smaller with transepithelial PRK than
with femtosecond-assisted LASIK, indicating less of a biomechanical effect with
transepithelial PRK.
PMID- 29335094
TI - Clinical outcomes of laser in situ keratomileusis with an aberration-neutral
profile centered on the corneal vertex comparing vector planning with manifest
refraction planning for the treatment of myopic astigmatism.
AB - PURPOSE: To evaluate clinical outcomes of laser in situ keratomileusis (LASIK)
with an aberration-neutral profile centered on the estimated visual axis
(considering 70% of the pupil offset toward the corneal vertex) comparing vector
planning with manifest refraction planning for the treatment of myopic
astigmatism. SETTING: Muscat Eye Laser Center, Muscat, Sultanate of Oman, Muscat,
Oman. DESIGN: Retrospective case series. METHODS: The outcomes were evaluated at
a 6-month follow-up in eyes showing ocular residual astigmatism (ORA) over 0.75
diopters (D) preoperatively. RESULTS: Eighty-five treatments were based on
manifest astigmatism (preoperative sphere -2.11 D +/- 1.3 [SD], cylinder -0.90 +/
1.0 D), and 79 treatments were based on vector planning (preoperative sphere
2.46 +/- 1.5 D, cylinder -0.78 +/- 0.79 D). At a 6-month follow-up, 128 patients
(164 eyes) were evaluated and no significant differences were observed between
the 2 groups in terms of difference between corrected distance visual acuity and
uncorrected distance visual acuity (UDVA) (P = .1, t test and Fisher exact test
Snellen lines 1 or better, P = .4) and postoperative UDVA (P = .05, t test and
Fisher exact test for UDVA 20/16 or better, P = .3). Significant differences were
observed between the 2 groups in terms of achieved spherical equivalent (P =
.04), corneal toricity, and ORA (P < .001, t test and Fisher exact test for ORA
<=0.75 D, P < .001). CONCLUSION: Performing LASIK for myopic astigmatism with the
vector planning approach resulted in comparable visual outcomes to manifest
refraction planning.
PMID- 29335095
TI - Vector analysis of astigmatic changes and optical quality outcomes after
wavefront-guided laser in situ keratomileusis using a high-resolution
aberrometer.
AB - PURPOSE: To assess the ocular optical quality results as well as the astigmatic
changes after wavefront-guided laser in situ keratomileusis (LASIK) in eyes with
myopic astigmatism. SETTING: Instituto Clinico-Quirurgico Oftalmologico, Bilbao,
Vizcaya, Spain. DESIGN: Prospective case series. METHODS: Thirty-three eyes
having wavefront-guided LASIK with the Star S4IR excimer laser combined with the
iDesign system were enrolled in the study. Changes in visual acuity, refraction,
higher-order aberrations, and ocular scattering index (OSI) were evaluated during
a 3-month follow-up. The Alpins method was used to analyze the astigmatic
changes. RESULTS: A significant reduction was observed in refraction (P < .001),
with significant improvement in uncorrected (UDVA) and corrected (CDVA) distance
visual acuities (P < .001). All eyes had a spherical equivalent within +/-0.50
diopter (D) and UDVA of 20/25 or better at 90 days after surgery. A total of
27.3% of eyes gained lines of CDVA. No significant changes were observed in
primary coma and spherical aberration (P >= .551). Likewise, no significant
changes were observed in OSI (P = .361), with a mean 90-day postoperative value
of 0.66 +/- 0.58 (SD). A significant change to negative values of the magnitude
of error (P = .007) and a significant decrease in the correction index (P = .004)
were observed during the follow-up, with mean 90-day postoperative values of
0.24 +/- 0.28 D and 0.86 +/- 0.17 D, respectively. CONCLUSION: Wavefront-guided
LASIK using a high-resolution aberrometer provided safe and efficacious
correction of myopic astigmatism, with preservation of the ocular optical
quality.
PMID- 29335096
TI - Clinically significant laser in situ keratomileusis flap striae.
AB - PURPOSE: To describe the incidence, risk factors, and outcomes before and after
irrigation of clinically significant laser in situ keratomileusis (LASIK) flap
striae. SETTING: Multisurgeon multicenter standardized protocol practice. DESIGN:
Retrospective case-control series. METHODS: Eyes with striae necessitating flap
relift and irrigation were identified. Preoperative, intraoperative, and
postoperative variables were collected. Incidence, risk factors, and outcomes
were assessed. RESULTS: Of the 109 403 eyes that had LASIK, the incidence of
striae-treated eyes was 0.79% (n = 875), with 8.7% irrigated the first hour after
surgery. The preoperative spherical equivalent (SE) and ablation depth
exponentially increased the striae risk (R2 = 0.9674; P < .001). Striae induced a
small hyperopic shift that reversed after the relift (mean 0.22 diopter [D] +/-
0.52 [SD] versus -0.02 +/- 0.45 D) (P < .001). After relifting, 68.0%, 87.0%, and
96.0% of eyes had an uncorrected distance visual acuity (UDVA) of 20/20, 20/25,
20/40 or better versus 25.0%, 55.0%, and 84.0%, respectively, before the relift
(P < .001). Thirteen percent fewer striae-treated eyes achieved a UDVA of 20/20.
Before relifting, 51.0% of striae eyes lost 1 or more lines of corrected distance
visual acuity, with a safety index reverting to control values (0.99 versus 1.00)
(P > .05) after the relift. A laser refractive enhancement was performed in 6.28%
of relifted striae eyes versus 3.04% in nonstriae control eyes. CONCLUSIONS: Flap
striae requiring surgeon intervention occurred in 0.79% of eyes. Higher
preoperative SE values were associated with an exponential increase risk for
striae. Treatment by lifting and irrigation significantly improved the accuracy,
efficacy, and safety to a level close to that of contralateral control eyes,
although striae-treated eyes were more likely to need excimer laser retreatment.
PMID- 29335097
TI - Aspheric versus wavefront-guided aspheric photorefractive keratectomy in eyes
with significant astigmatism.
AB - PURPOSE: To compare the refractive and higher-order aberrations (HOAs) outcomes
after photorefractive keratectomy (PRK) in patients with significant astigmatism
using aspheric versus wavefront-guided aspheric profiles. SETTING: Ophthalmic
Research Center and Department of Ophthalmology, Shahid Beheshti University of
Medical Sciences, Negah Eye Hospital, Tehran, Iran. DESIGN: Prospective
randomized case series. METHODS: One eye of each patient with a refractive
astigmatism more than 2.00 diopters (D) randomly received aspheric PRK. In the
other eye, wavefront-guided and aspheric treatment was performed using a
personalized treatment advanced algorithm. Visual acuity, refractive errors, and
HOAs were compared between the 2 groups preoperatively and 12 months
postoperatively. RESULTS: The study comprised 32 patients (64 eyes). The mean
preoperative refractive astigmatism was -4.07 D +/- 1.64 (SD) and -4.02 +/- 1.55
D in the aspheric group and wavefront-guided aspheric group, respectively (P =
.2). The mean postoperative astigmatism was -0.46 +/- 0.37 D and -0.82 +/- 0.53 D
in the aspheric group and wavefront-guided aspheric group, respectively (P =
.02). Postoperatively, the root mean square of total HOAs was significantly
increased in both groups. However, compared with wavefront-guided aspheric PRK,
aspheric PRK induced fewer HOAs (P = .003). CONCLUSIONS: In eyes with high
astigmatism, post-PRK residual astigmatism was lower in the aspheric group than
in the wavefront-guided aspheric group. The increase in HOAs was significantly
higher in the wavefront-guided aspheric group than in the aspheric group.
PMID- 29335098
TI - Factors affecting corneal incision position during femtosecond laser-assisted
cataract surgery.
AB - PURPOSE: To compare the expected versus actual position and dimension of corneal
incisions during femtosecond laser-assisted cataract surgery. SETTING: Private
Ophthalmic Clinic, Sydney, NSW, Australia. DESIGN: Retrospective case series.
METHODS: Video recordings of femtosecond laser-assisted cataract surgery with a
Lensx laser were reviewed. The deviation of the main and 2 secondary incisions
from the expected position were correlated with globe tilt, globe displacement,
and biometric data. The globe tilt was inferred from anterior capsule tilt. Globe
displacement was measured. The Softfit contact lens thickness used in the patient
interface was measured separately. RESULTS: The primary incision internal and
external exits were within 142 MUm +/- 70 (SD) and 151 +/- 75 MUm of the planned
position. The dimensions and position did not correlate with biometric variables.
The superior secondary incision external exit was displaced centrally (321 +/- 84
MUm) and the internal exit was displaced peripherally (84 +/- 102 MUm). The
inferior secondary incision external exit was displaced centrally (278 +/- 142
MUm) and the internal exit was displaced peripherally (190 +/- 133 MUm).
Multivariate analysis showed that the external and internal exits of the superior
(adjusted r2 = 0.36, P < .001; r2 = 0.15, P < .001) and inferior secondary
incisions (r2 = 0.67, P < .001; r2 = 0.46, P < .001) correlated with globe tilt
and displacement. CONCLUSIONS: The primary incisions were close to the expected
dimensions. The secondary incision position was affected by eye tilt and
eccentric docking. These could potentially be improved with optical coherence
tomography guidance.
PMID- 29335099
TI - Femtosecond laser-assisted cataract surgeries reported to the European Registry
of Quality Outcomes for Cataract and Refractive Surgery: Baseline
characteristics, surgical procedure, and outcomes.
AB - PURPOSE: To describe a large cohort of femtosecond laser-assisted cataract
surgeries in terms of baseline characteristics and the related outcomes. SETTING:
Eighteen cataract surgery clinics in 9 European countries and Australia. DESIGN:
Prospective multicenter case series. METHODS: Data on consecutive eyes having
femtosecond laser-assisted cataract surgery in the participating clinics were
entered in the European Registry of Quality Outcomes for Cataract and Refractive
Surgery (EUREQUO). A trained registry manager in each clinic was responsible for
valid reporting to the EUREQUO. Demographics, preoperative corrected distance
visual acuity (CDVA), risk factors, type of surgery, type of intraocular lens,
visual outcomes, refractive outcomes, and complications were reported. RESULTS:
Complete data were available for 3379 cases. The mean age was 64.4 years +/- 10.9
(SD) and 57.8% (95% confidence interval [CI], 56.1-59.5) of the patients were
women. A surgical complication was reported in 2.9% of all cases (95% CI, 2.4
3.5). The mean postoperative CDVA was 0.04 +/- 0.15. logarithm of the minimum
angle of resolution. A biometry prediction error (spherical equivalent) was
within +/-0.5 diopter in 71.8% (95% CI, 70.3-73.3) of all surgeries.
Postoperative complications were reported in 3.3% (95% CI, 2.7-4.0). Patients
with good preoperative CDVA had the best visual and refractive outcomes; patients
with poor preoperative visual acuity had poorer outcomes. CONCLUSIONS: The visual
and refractive outcomes of femtosecond laser-assisted cataract surgery were
favorable compared with manual phacoemulsification. The outcomes were highly
influenced by the preoperative visual acuity, but all preoperative CDVA groups
had acceptable outcomes.
PMID- 29335100
TI - Risk factors for and management of pupillary intraocular lens capture after
intraocular lens transscleral fixation.
AB - PURPOSE: To analyze risk factors and management of pupillary intraocular lens
(IOL) capture after IOL transscleral fixation. SETTING: Department of
Ophthalmology, Seoul National University Hospital, Seoul, South Korea. DESIGN:
Retrospective case series. METHODS: A chart review was performed of patients who
had transscleral fixation of IOLs between January 1, 2012, and December 31, 2013.
Eyes were divided into 2 groups depending on whether the IOL was pupillary
captured. Perioperative corrected distance visual acuity (CDVA), intraocular
pressure (IOP), spherical equivalent (SE) with refraction, axial length (AL), and
total follow-up time were compared between the 2 groups. Ultrasound biomicroscopy
images were used to analyze iris morphology and IOL position. RESULTS: The chart
review identified 138 patients, 112 patients of whom were included in this
analysis. The preoperative and final mean CDVA, IOP, SE, AL, and most iris
morphologic parameters were not significantly different between the 2 groups. In
the pupillary capture IOL group, the mean age of patients with was younger, the
anterior chamber depth (ACD) was narrower, and the rate of reverse pupillary
block was higher (P = .003, P = .03, and P = .016, respectively). Intraocular
lens decentration in the captured group was significantly larger (P = .002).
Multiple logistic regression analysis showed that ACD, reverse pupillary block,
and main decentration were associated with pupillary capture of the IOL.
CONCLUSIONS: Pupillary capture of an IOL occurred more in eyes with reverse
pupillary block and poor IOL positioning. Accordingly, laser iridotomy must be
considered for treatment.
PMID- 29335101
TI - Outcomes and complication rates of primary resident-performed cataract surgeries
at a large tertiary-care county hospital.
AB - PURPOSE: To identify the preoperative risk factors, intraoperative events, and
postoperative complications increasing the risk for poor visual outcomes in
resident-performed cataract surgeries at a tertiary-care county hospital.
SETTING: Ben Taub General Hospital, Houston, Texas, USA. DESIGN: Retrospective
case series. METHODS: Resident-performed cataract surgeries were analyzed for
risk factors, comorbidities, and intraoperative and postoperative complications.
The main outcome measures were preoperative and postoperative uncorrected
distance visual acuity and corrected distance visual acuity (CDVA), which were
correlated with preoperative demographics, intraoperative and postoperative
events, and resident training level. The data were subdivided into cases without
events and cases with events to determine which complications led to poor visual
outcomes. RESULTS: The study analyzed 1290 resident-performed cataract surgeries.
The mean visual acuity improved significantly after surgery in all patients (P <
.001), with 80.5% of patients without complications and 70.7% with complications
attaining a CDVA of 20/40 or better (P < .002). Poor visual outcomes were
associated with alpha-antagonist use (P = .043) and pseudoexfoliation syndrome (P
= .001). The most common intraoperative complications were vitreous loss (6.7%)
and posterior capsule tear (7.0%). The mean postoperative visual acuity did not
vary by trainee year, and the rate of dropped nucleus during surgery declined as
residents progressed in training (P < .05). All other complication rates were
similar between levels of training. CONCLUSION: Despite more complicated
cataracts and advanced comorbidities, primary resident-performed cataract surgery
in a tertiary-care county hospital system achieved visual outcomes and
complication rates similar to those found in other training hospitals.
PMID- 29335102
TI - Comparison of 2 laser fragmentation patterns used in femtosecond laser-assisted
cataract surgery.
AB - PURPOSE: To evaluate the effect of fragmentation patterns (pie pattern versus
grid pattern) on effective phacoemulsification time (EPT). SETTING: Department of
Ophthalmology, Goethe University, Frankfurt am Main, Germany. DESIGN:
Retrospective case series. METHODS: Eyes that had femtosecond laser-assisted
cataract surgery were included. One half of the group was treated with the pie
pattern. The preoperative lens density was evaluated by Scheimpflug imaging
(Pentacam). Then, the eyes treated with the grid pattern were matched to the pie
pattern group based on lens density (Scheimpflug imaging). RESULTS: The study
comprised 150 eyes (75 in the pie-pattern group and 75 in the grid pattern
group). The mean patient age was 66 years +/- 10.67 (SD). The Scheimpflug density
zone was 10.05% +/- 1.52%. The mean EPT was 6.63 +/- 5.41 seconds for the pie
pattern, significantly higher than the 4.26 +/- 6.99 seconds for the grid pattern
(P < .01, Wilcoxon rank-sum test). The number of eyes with EPT = 0 was
significantly higher with grid pattern (37 for grid versus 1 for pie, P < .01,
chi2 test). Regression analysis showed that the EPT was significantly dependent
on lens density for both methods (P = .045 for pie versus P < .01 for grid). In
eyes with a lens density higher than 12% (9 eyes in each group), the pie pattern
showed significantly lower EPT (P = .02, Wilcoxon rank-sum test). CONCLUSIONS: In
cases of low to moderate lens density, grid fragmentation pattern should be used
because the EPT was significantly lower and a significantly higher number of eyes
did not require further emulsification. However, in eyes with high density
(>12%), pie-pattern fragmentation is recommended.
PMID- 29335103
TI - New objective lens density quantification method using swept-source optical
coherence tomography technology: Comparison with existing methods.
AB - PURPOSE: To assess a new objective cataract grading method based on lens
densitometry on swept-source optical coherence tomography (SS-OCT) scans provided
by the IOLMaster 700. SETTINGS: Rothschild Foundation, Paris, France. DESIGN:
Prospective case series. METHODS: All patients consulting for cataract evaluation
who provided their consent to participate in the study were included. A history
of eye surgery, corneal or retinal disorders, and ocular dryness were exclusion
criteria. The average lens densitometry was measured with SS-OCT scans using
ImageJ software. The ocular scatter index (OSI) measured with a double-pass
aberrometer (Optical Quality Analysis System), the Pentacam nucleus staging
(hereafter referred to as nuclear staging) score, and mean nuclear staging were
also measured and compared with the mean lens densitometry. RESULTS: One hundred
ten eyes (51 with cataract and 59 controls) were included. The average lens
densitometry measurements were repeatable (P = .99, analysis of variance). The
repeatability limit was 2.50 pixel units. The average lens density was correlated
with the OSI (r2 = 0.52, P < .01), nuclear staging score (r2 = 0.75, P < .01),
and mean nuclear staging (r2 = 0.41, P < .01). An average lens density greater
than 82.9 pixel units was the cutoff threshold for cataract, with a sensitivity
of 73.9% and a specificity of 91.2%. CONCLUSIONS: The average lens density
measured by SS-OCT was a repeatable and reliable objective cataract grading
method. It was correlated with OSI measurement. If the average lens density was
greater than 82.9 pixel units and the patient reported visual impairment,
cataract surgery might be discussed.
PMID- 29335104
TI - Vision-related quality of life and dependency in French keratoconus patients:
Impact study.
AB - PURPOSE: To assess the quality of life in French keratoconus patients. SETTING:
Fifty-seven Keratoconus National Reference Centers across France. DESIGN:
Prospective case series. METHODS: Patients completed the National Eye Institute
Visual Functioning Questionnaire-25 (NEI VFQ-25) and a French validated
questionnaire on disability and dependency from February to June 2012 when they
came for an ophthalmic examination at 57 participating centers across France. An
ocular examination including refraction, corneal topography, pachymetry, and
slitlamp biomicroscopy was performed. The composite or global NEI VFQ-25 score
and the proportion of patients who were dependent (defined by the difficulties
with activities of daily living) because of keratoconus were the main evaluation
criteria in this study. RESULTS: The study comprised 550 keratoconus patients.
Women, corrected distance visual acuity worse than 20/40, steep keratometry
higher than 52.0 diopters, history of surgery (corneal transplant, intrastromal
corneal ring segments, or corneal crosslinking), and more severe keratoconus
according to the Amsler-Krumeich classification were associated with an
increasingly negative impact on quality of life (overall scores are significantly
lower). Moreover, 4.9% of participants reported having changed their jobs because
of keratoconus and 7.8% received keratoconus-related disability. Sixty-nine
(12.5%) patients reported having difficulties with activities of daily living and
are considered dependent. CONCLUSION: Keratoconus was associated with a
significant reduction in quality of life but it did not result in social
exclusion.
PMID- 29335105
TI - Optimization and comparison of a 0.7 mm tip with the 0.9 mm tip on an active
fluidics phacoemulsification platform.
AB - PURPOSE: To assess the effect of varying levels of torsional power on
phacoemulsification efficiency using an active-fluidics phacoemulsification
platform with a 0.7 mm Sonata tip. SETTING: John A. Moran Eye Center
Laboratories, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental
study. METHODS: A 0.7 mm tip was used to emulsify 2.0 mm porcine lenses that had
been hardened in formalin. The torsional power was varied from 10% to 100% at
intervals of 10%, and efficiency and chatter were recorded. A comparison of the
0.7 mm tip with the 0.9 mm Balanced tip was also performed. Using a torsional
power setting of 90% and 100%, the 0.7 mm tip and the 0.9 mm tip efficiency times
were recorded. RESULTS: The study showed an increase in efficiency as torsional
power increased. The relationship was linear and more efficient up to 90% (R2 =
.8025, P = .0005). Chatter was only observed at a torsional power setting of 60%.
In addition, a head-to-head comparison of the 0.7 mm tip with the 0.9 mm tip
showed that both tips were statistically similar in efficiency times, despite the
smaller diameter of the 0.7 mm tip. CONCLUSIONS: The optimum torsional power
setting with the Centurion platform in conjunction with the 0.7 mm tip was 90%.
The efficiency of the 0.7 mm tip and the 0.9 mm tip was statistically similar.
PMID- 29335106
TI - Preoperative optimization of ocular surface disease before cataract surgery.
AB - An impaired ocular surface adversely affects preoperative planning for cataract
surgery, including intraocular lens (IOL) calculations, toric IOL axis and
magnitude estimates, keratometry, and topography measurements. It also increases
surgical difficulty. We performed a review to evaluate the connection between
cataract surgery and dry eye and to determine the best management for these
patients. Of the 16 papers included in this review, 6 were randomized controlled
trials. Cataract surgery was shown to worsen ocular parameters and aggravate dry
eye disease. Physicians should recognize and aggressively treat cataract patients
with poor prognostic factors and/or with existing dry-eye disease. Increased
incision extent, operation time, irrigation, and microscopic-light exposure time
decreased the tear breakup time and mean goblet cell density. Postoperatively,
the use of eyedrops was associated with worsening of goblet cell density; hence,
these medications should be tapered off when no longer needed.
PMID- 29335107
TI - Surgical removal of dystrophic calcification on a silicone intraocular lens in
association with asteroid hyalosis.
AB - We present a case of successful removal of late calcium deposition on the
posterior surface of a silicone intraocular lens (IOL) optic in association with
asteroid hyalosis using a surgical technique that included pars plana vitrectomy,
a lighted pick, and a modified silicone-tipped cannula. The lighted pick provided
the most efficient and complete removal of calcium deposits. Postoperatively, the
dystrophic calcification was removed and the IOL optic was clear at 6 months
follow-up. The patient's symptoms resolved and uncorrected distance visual acuity
returned to 20/20. This method can be considered in patients with dystrophic
calcification of a silicone IOL in association with asteroid hyalosis and might
avoid the need for IOL exchange and its associated complications and uncertain
refractive outcomes.
PMID- 29335108
TI - Cataract morphology and risk for glaucoma after cataract surgery in infants with
unilateral congenital cataract.
PMID- 29335109
TI - Trypan blue-assisted microinvasive glaucoma surgery.
PMID- 29335110
TI - December consultation #2.
PMID- 29335111
TI - Corneal asymmetry associated with stromal opacity after previous laser in situ
keratomileusis: December consultation #1.
PMID- 29335112
TI - December consultation #3.
PMID- 29335114
TI - December consultation #5.
PMID- 29335113
TI - December consultation #6.
PMID- 29335115
TI - December consultation #4.
PMID- 29335116
TI - Editor's Comment.
PMID- 29335117
TI - December consultation #7.
PMID- 29335118
TI - Management of subluxated intraocular lens-capsular bag complex.
PMID- 29335119
TI - Reply.
PMID- 29335120
TI - Differentiating retinal tear and detachment rate by axial length to identify at
risk patients having neodymium:YAG capsulotomy.
PMID- 29335121
TI - Letter to the Editor: Proceedings from the USDA and National Dairy Council
Collaborative Research Planning Meeting Held August 24, 2016.
PMID- 29335122
TI - ?
PMID- 29335123
TI - ?
PMID- 29335124
TI - [The reception, a prerequisite of the encounter: a political question].
AB - The reception of a patient in psychiatry is a stage which consists of more than a
single initial contact between a person suffering psychologically and a
caregiver. This time can open the way to an encounter, without which a care
relationship cannot be established. The reception as a paradigm of psychiatric
care questions the concept of this care, at a time when caregivers cannot avoid
the question of their political engagement.
PMID- 29335125
TI - [The end of the asylum, a change in representations].
AB - Through the major changes which the psychiatric hospital has undergone throughout
history, the question is raised of the identity of caregivers, what the
psychiatric asylum provides as a response to mental illness, and the function of
the asylum as a place for receiving and then caring for patients, within society.
These radical changes, which undermine the narcissism of caregivers, have
consequences both within the psychiatric hospital and society as a whole.
Consequences which question the very notion of care in a post-modern society.
PMID- 29335126
TI - [Reception of the patient in psychiatry: overcoming the narcissistic test of the
caregiver].
AB - The theme of the encounter is addressed through the question of the reception of
the patient. This encounter forces the caregiver to consider his or her own
identity faced with the patient, to adjustments which can elude narcissistic
doubts by resorting to the standardisation of care. Possible ways for the
construction of a joint project are then considered. A 'common illusion' of care,
which ensures that the encounter, a prelude to the possibility of care, is
achieved.
PMID- 29335127
TI - [Accessing the sensitive part of the Being before us].
AB - The acceleration of the standardisation of care and the dominance of the quality
approach, since the 1990s, have brought significant changes to nursing practices,
the different therapeutic approaches and the 'place' of caregivers with regard to
the patient. In this context of modern psychiatry which must comply with all
kinds of recommendations, what is the situation of the patient suffering from
psychosis, who would previously have been supported over the long term in a
psychopathological process? The encounter, envisaged as an opening, is placed at
the heart of the therapeutic relationship.
PMID- 29335129
TI - [A tale of two encounters].
AB - The moving testimony of a patient shows the impact which a successful encounter
can have. Beyond the positive clinical consequences, her rediscovered motivation
and pleasure are the essential drivers which have guided her along the pathway of
reconstruction. A tale of two encounters which have marked her life course.
PMID- 29335128
TI - [Risking the encounter].
AB - In their daily practice, psychiatric caregivers seek an encounter with the
patient. This involves trying to understand the patient's suffering, to give
meaning and to make the clinical connection. This equates to constructing
together. Some care organisations are working to create spaces within units which
are suited to receiving patients with an atmosphere favouring the encounter. The
story of Baptiste illustrates this approach. Testimony.
PMID- 29335130
TI - [Body marking in psychosis].
AB - Patients with psychosis speak of an uneasy relationship with their body. Between
feelings of too little and too much, for them it is a matter of trying to suture
an image which is not always unified, a body which they are not always sure they
have. The attentive clinician will attempt to support the solutions of each
psychotic patient to maintain their body, beyond the death drive which pushes
them to tear it apart.
PMID- 29335132
TI - ?
PMID- 29335131
TI - [Call for reinforcements, care to support clinical pertinence].
AB - In their day-to-day practice, psychiatric caregivers are frequently confronted
with difficult clinical situations, or crises, which require a rapid and
appropriate nursing response. While most of these situations are managed and
contained by the professionals present, others will require, depending on their
criticality, outside help in order to guarantee greater clinical pertinence and a
safe environment.
PMID- 29335133
TI - ?
PMID- 29335134
TI - ?
PMID- 29335135
TI - [Nursing home, caregiving practice and new work organisation].
AB - The recent ageing of the population is resulting in a corresponding increase in
the functional dependence of elderly people. Nursing homes hosting this specific
population must adapt to this new profile of resident and their arrival at an
increasingly older age. Caregiving tasks are becoming more cumbersome affecting
the working conditions of caregivers who also face the new management approaches
which are imposed.
PMID- 29335136
TI - [Life project of residents and institutional approach in nursing homes].
AB - The life project in a nursing home involves all the players concerned: first of
all, the resident, then the caregivers, the families and the institution. This
unifying tool, organised around the elderly, helps to develop collective
competencies, favours the integration of new residents and reassures families.
This article presents a nursing home's experience of setting up a life project.
PMID- 29335137
TI - [Nutritional status of residents of a nursing home and optimisation of the
working time of caregivers].
AB - The lack of time to devote to care is a frequent complaint of nurses and nursing
assistants. The results of a study show that an improvement in the nutritional
status of nursing home residents could help to improve their quality of life and
to optimise the working time of the nursing teams, thanks to the reduction of
pressure ulcers, diarrhoea, falls, fractures and infections.
PMID- 29335138
TI - [Intrafamily conflicts and family-caregiver tensions in a nursing home].
AB - Conflicts between families and caregivers in a nursing home have multiple causes
centred (but not exclusively) on the interest of the resident. Intrafamily
conflicts can lead to tensions between families and caregivers. Alzheimer's
disease changes the relations with the patient's family members when they are
involved in the care, which can lead to a division within the family. This
article discusses the sources of difficulties between families and caregivers and
ways of managing and above all preventing them.
PMID- 29335139
TI - [The analogon, a caregiving resource in geriatric psychiatry].
AB - Few caregivers know what analogons are, yet they use them on occasion,
intuitively, for the benefit of their patients. An analogon, an identifying
object, enables patients with cognitive disorders to 'decipher' their environment
and find meaning in it. Caregivers sometimes use analogons without being aware of
the theory behind them.
PMID- 29335140
TI - [The sexualisation of the care relationship by the patient in gerontology].
AB - The expression of the sexuality of the ageing patient in the care setting,
particularly when it concerns the genital area and involves the caregiver without
he or she being aware, constitutes a critical situation for the geriatric teams.
A psychodynamic reading of these situations is important for the caregiving teams
in order to optimise the somatic treatment and to prevent the risk of an
unsuitable reactive treatment. This article presents a clinical case as an
example.
PMID- 29335141
TI - ?
PMID- 29335142
TI - ?
PMID- 29335143
TI - ?
PMID- 29335144
TI - ?
PMID- 29335145
TI - [The place of separations in a child's development].
AB - The issue of separation follows a specific process in the course of a child's
development. Putting in place the intersubjective distance and primitive links
marks the process of differentiation, falling short of actual separation.
Therapeutic separations can be restorative and structuring, under certain
conditions. The role of professionals is to ensure that the separations do not
simply constitute 'bad encounters'.
PMID- 29335146
TI - [Supporting the encounter of mothers suffering from borderline conditions with
their baby].
AB - Mothers suffering from borderline conditions are overwhelmed by emotions. Their
interactions are tainted with qualitative discontinuities, unpredictable for
infants. These high-risk situations must not be trivialised. They are
characterised by the importance of providing rapid support to the baby and by the
existence of maternal suffering. The infant's basic needs guide the professionals
working with these families.
PMID- 29335147
TI - [Pre- and postnatal support through haptonomy].
AB - Pre- and postnatal haptonomy constitutes a quality form of support for babies and
their parents, from the final months of pregnancy through to the acquisition of
walking. It contributes to the development of infants' emotional, sensory and
tonic-postural security, enabling them to start to move and engage with
confidence in life and in relationships.
PMID- 29335148
TI - [Access to language, encounters and separations].
AB - Access to language is part of the extension of a preverbal relationship with one
or several partners. This relationship, present from birth, is founded on
extremely sophisticated innate competencies. Oral language is both an instrument
of encounter with those around us and a means of separating ourselves from others
harmlessly, thanks to the symbolic value of words and the process of
internalisation which they allow.
PMID- 29335149
TI - [Learning to separate together, the separation-individuation group].
AB - The 'separation-individuation' group is offered to children aged between three
and five, in outpatient consultations with a paediatric psychiatrist. It was
created following the testimonies of early childhood professionals describing the
feeling on the part of parents of being torn from their child, during the first
year of school. Open and held on a weekly basis, it is combined with a parents'
meeting organised simultaneously. The individualised group tool supports the
separation-individuation process when this is particularly painful, for the child
and the parents.
PMID- 29335150
TI - [Birth and separation, questioning caesarean deliveries on maternal request].
AB - Clinical practice and literature highlight the emergence and the growth in the
number of caesareans carried out on the request of the mother without medical
indication. For some women, a vaginal delivery is an anachronism, while for
others it is a necessary passage towards motherhood. A reflection was carried out
to illustrate the singularity behind these requests and attempt to overcome the
'for' and 'against' divide.
PMID- 29335151
TI - [Tools to overcome anxiety in paediatric surgery].
AB - An association of caregivers carried out several actions to combat children's
anxiety in paediatric surgery, including anaesthetic masks to cover in stickers,
a tactile application on the operating pathway and a cuddly toy in the recovery
room. These tools help children at the moment of being separated from their
parents and all along their care pathway. They also encourage caregivers to
adjust their practices to improve the care provided to the families.
PMID- 29335152
TI - ["I foster babies awaiting adoption."]
AB - A mother's decision to give up a child is followed by a two-month period during
which she may go back on her decision. During this time, the baby may be cared
for in a care home or placed with a specialist foster family. An interview with
Christiane Hamel, a retired children's nurse who has chosen to foster children in
her home.
PMID- 29335153
TI - [The sitting position during peripheral venipunctures in young children, a
practice to develop].
AB - The children's nurse has several missions including that of caring for the child
in a holistic approach, ensuring their physical safety and psychological
security. When performing peripheral venipunctures in young children, caregivers
must implement strategies to relieve pain and prevent psychological traumas which
may generate stress for subsequent care procedures. In a paediatric unit, their
observations and analysis have improved children's experience of this invasive
procedure, with a need for less restraint. In this context, the sitting position
seems beneficial for the young patient.
PMID- 29335154
TI - Local administration of Tiludronic Acid downregulates important mediators
involved in periodontal tissue destruction in experimental periodontitis in rats.
AB - OBJECTIVE: The purpose of this study was to evaluate whether local administration
of TIL could influence the expression of the inflammatory mediators IL-1beta, TNF
alpha, MMP-8 and COX-2 in rats with experimental periodontitis (EP). METHODS:
Twenty-four adult male rats (Rattus norvegicus, albinus, Wistar) were assigned to
groups C, EP, EP-TIL (CControl group, EP-Periodontitis groups). On EP groups, a
ligature was placed around maxillary 2nd molars on day 1. On group EP-TIL, 20 MUL
of TIL solution (1 mg/kg body weight) was injected into the subperiosteal palatal
area adjacent to the maxillary 2nd molar every other day until euthanasia (day
11). Alveolar bone loss was morphometrically analyzed. mRNA expressions of IL
1beta, TNF-alpha, MMP-8 and COX-2 were assessed by qPCR. IL-1beta, TNF-alpha, MMP
8 and COX-2 were immunohistochemically analyzed. Data were analyzed
statistically. RESULTS: Group EP-TIL presented reduced alveolar bone loss when
compared with group EP (p < 0.05). Group EP-TIL presented decreased mRNA
expressions of IL-1beta, TNF-alpha, MMP-8 and COX-2 and reduced immunolabeling of
IL-1beta, TNF-alpha and MMP-8 when compared with group EP (p < 0.05). No
differences regarding the immunolabeling of COX-2 were found when group EP-TIL
was compared with the other groups (p > 0.05). CONCLUSION: Within the limits of
this study, it can be concluded that local administration of TIL downregulates
important mediators involved in periodontal tissue destruction in ligature
induced periodontitis in rats.
PMID- 29335155
TI - Investigating the potential impact of dose banding for systemic anti-cancer
therapy in the paediatric setting based on pharmacokinetic evidence.
AB - BACKGROUND: To make systemic anti-cancer therapy (SACT) preparation more
practicable, dose-banding approaches are currently being introduced in many
clinical centres. The present study aimed to determine the potential impact of
using recently developed National Health Service in England (NHSE) dose-banding
tables in a paediatric setting. METHODS: Using pharmacokinetic parameters
obtained from 385 drug administrations in 352 children aged from 1 month to 18
years, treated with five drugs (dactinomycin, busulfan, carboplatin,
cyclophosphamide and etoposide), individual exposures (area under the plasma drug
concentration versus time curve; AUC) obtained using doses rounded according to
the published NHSE tables were calculated and compared with those obtained by
standard dose calculation methods. RESULTS: For all five drugs, the relative
variation between the NHSE dose and the recommended dose (RecDose) (standard
individually calculated dose) was between -6% and +5% as expected. In terms of
AUC, there was no statistically significant difference in precision between
exposures obtained by the RecDose and those obtained with dose banding (absolute
value of relative difference 15-34%). CONCLUSION: Based on pharmacokinetic data
for these five drugs, the results generated support the implementation of NHSE
dose-banding tables. Indeed, inter-patient variability in drug clearance and
exposure far outweighs the impact of relatively small drug dose changes
associated with dose banding.
PMID- 29335157
TI - Thermal and epithermal neutron flux distributions measurement in thermal column
of TRR using an experimental-simulation method.
AB - For designing an appropriate neutron beam, the determination of neutron flux at
any irradiation facility is an important key factor. Due to the importance of
determining the thermal and epithermal neutron fluxes in a typical thermal column
of a reactor, a simple and accurate technique is introduced in this study.
Absolute thermal and epithermal fluxes were measured experimentally at a certain
point using the foil activation method by neutron bombardment of bare and cadmium
covered Au foils. The relative neutron fluxes were also derived simply by means
of Monte Carlo simulation by accurate modelling of the reactor components.
Finally, by normalization of the relative distribution flux with regard to
information about the absolute neutron flux, the accurate thermal and epithermal
neutron distributions were derived, separately.
PMID- 29335156
TI - Adapting cervical cancer screening for women vaccinated against human
papillomavirus infections: The value of stratifying guidelines.
AB - BACKGROUND: Several countries have implemented vaccination against human
papillomavirus (HPV) for adolescent girls and must decide whether and how to
adapt cervical cancer (CC) screening for these low-risk women. We aimed to
identify the optimal screening strategies for women vaccinated against HPV
infections and quantify the amount that could be spent to identify vaccination
status among women and stratify CC screening guidelines accordingly. METHODS: We
used a mathematical model reflecting HPV-induced CC in Norway to project the long
term health benefits, resources and costs associated with 74 candidate-screening
strategies that varied by screening test, start age and frequency. Strategies
were considered separately for women vaccinated with the bivalent/quadrivalent
(2/4vHPV) and nonavalent (9vHPV) vaccines. We used a cost-effectiveness framework
(i.e. incremental cost-effectiveness ratios and net monetary benefit) and a
commonly-cited Norwegian willingness-to-pay threshold of ?75,000 per quality
adjusted life-year gained. RESULTS: The most cost-effective screening strategy
for 9vHPV- and 2/4vHPV-vaccinated women involved HPV testing once and twice per
lifetime, respectively. The value of stratifying guidelines by vaccination status
was ?599 (2/4vHPV) and ?725 (9vHPV) per vaccinated woman. Consequently, for the
first birth cohort of ~22,000 women who were vaccinated in adolescence in Norway,
between ?10.5-13.2 million over their lifetime could be spent on identifying
individual vaccination status and stratify screening while remaining cost
effective. CONCLUSION: Less intensive strategies are required for CC screening to
remain cost-effective in HPV-vaccinated women. Moreover, screening can remain
cost-effective even if large investments are made to identify individual
vaccination status and stratify screening guidelines accordingly.
PMID- 29335158
TI - Arvanil, olvanil, AM 1172 and LY 2183240 (various cannabinoid CB1 receptor
agonists) increase the threshold for maximal electroshock-induced seizures in
mice.
AB - BACKGROUND: Recent evidence reveals therapeutic potential for cannabinoids to
reduce seizure frequency, severity and duration. Animal models are useful tools
to determine the potential antiseizure or antiepileptic effects of cannabinoids.
The objective of this study was evaluation of the effect of arvanil, olvanil, AM
1172 and LY 2183240, the compounds interacted with endocannabinoid and/or
endovanilloid systems, on convulsions in the commonly used model of convulsions
in mice. METHODS: Arvanil and olvanil were injected intraperitoneally (ip) 30min
and AM 1172 and LY 2183240 were administered ip 60min before the maximal
electroshock seizure threshold (MEST) test. The criterion for convulsant activity
was tonic hindlimb extension. RESULTS: Arvanil, olvanil, AM 1172 and LY 2183240
dose-dependently increased the electroconvulsive threshold in mice. The TID20
(threshold increasing dose 20) values for arvanil, olvanil, AM 1172 and LY
2183240 were 0.9, 2.18, 2.48 and 3.56mgkg-1, respectively, and the TID50
(threshold increasing dose 50) values were 1.88, 6.45, 6.29 and 10.04mgkg-1,
respectively. CONCLUSION: This study identified anticonvulsant effects of
arvanil, olvanil, AM 1172 and LY 2183240. The order of the magnitude of the
anticonvulsant effects of the examined compounds was following:
arvanil>olvanil>AM 1172>LY 2183240.
PMID- 29335159
TI - Repeated Domperidone treatment modulates pulmonary cytokines in LPS-induced acute
lung injury in mice.
AB - The dopaminergic antagonist drug Domperidone has immunomodulatory effects. We
investigated the effects of repeated Domperidone treatment in a model of
Lypopolyssacharide (LPS)-induced acute lung inflammation. Adult C57BL/6J mice
were treated with either Vehicle or Domperidone for 5days, and challenged
intranasally with LPS in the following day. The behavior of mice was analyzed in
the open field and elevated plus-maze test before and 24h after LPS challenge.
The bronchoalveolar lavage fluid, blood and lung tissue were collected 24h and
48h after LPS challenge. Domperidone treatment increased LPS-induced tumor
necrosis factor (TNF) and interleukin (IL)-6 production in the bronchoalveolar
lavage fluid, without altering tissue damage and the number of immune cells in
the lungs and circulation. Locomotor and anxiety-like behavior were unchanged
after Domperidone and/or LPS treatment. Cytokine data indicate that Domperidone
promotes a change in activity of other cell types, likely alveolar epithelial
cells, without affecting immune cell migration in the present model. Due to the
role of these cytokines in progression of inflammation, Domperidone treatment may
exacerbate a subsequent inflammatory injury.
PMID- 29335160
TI - Mobile phone use among patients and health workers to enhance primary healthcare:
A qualitative study in rural South Africa.
AB - Mobile phones have the potential to improve access to healthcare information and
services in low-resourced settings. This study investigated the use of mobile
phones among patients with chronic diseases, pregnant women, and health workers
to enhance primary healthcare in rural South Africa. Qualitative research was
undertaken in Mpumalanga in 2014. Semi structured in-depth interviews were
conducted with 113 patients and 43 health workers from seven primary healthcare
clinics and one district hospital. Data were thematically analysed. We found that
some health workers and patients used their own mobile phones for healthcare,
bearing the cost themselves. Patients used their mobile phones to remind
themselves to take medication or attend their clinic visits, and they appreciated
receiving voice call reminders. Some patients and health workers accessed
websites and used social media to gather health information, but lacked web
search strategies. The use of the websites and social media was intermittent due
to lack of financial ability to afford airtime among these patients and health
workers. Many did not know what to search for and where to search. Doctors have
developed their own informal mobile health solutions in response to their work
needs and lack of resources due to their rurality. Physical and social factors
influence the usability of mobile phones for healthcare, and this can shape
communication patterns such as poor eyesight. The bottom-up use of mobile phones
has been evolving to fill the gaps to augment primary care services in South
Africa; however, barriers to access remain, such as poor digital infrastructure
and low digital literacy.
PMID- 29335161
TI - Health equity monitoring for healthcare quality assurance.
AB - Population-wide health equity monitoring remains isolated from mainstream
healthcare quality assurance. As a result, healthcare organizations remain ill
informed about the health equity impacts of their decisions - despite becoming
increasingly well-informed about quality of care for the average patient. We
present a new and improved analytical approach to integrating health equity into
mainstream healthcare quality assurance, illustrate how this approach has been
applied in the English National Health Service, and discuss how it could be
applied in other countries. We illustrate the approach using a key quality
indicator that is widely used to assess how well healthcare is co-ordinated
between primary, community and acute settings: emergency inpatient hospital
admissions for ambulatory care sensitive chronic conditions ("potentially
avoidable emergency admissions", for short). Whole-population data for 2015 on
potentially avoidable emergency admissions in England were linked with
neighborhood deprivation indices. Inequality within the populations served by 209
clinical commissioning groups (CCGs: care purchasing organizations with mean
population 272,000) was compared against two benchmarks - national inequality and
inequality within ten similar populations - using neighborhood-level models to
simulate the gap in indirectly standardized admissions between most and least
deprived neighborhoods. The modelled inequality gap for England was 927
potentially avoidable emergency admissions per 100,000 people, implying 263,894
excess hospitalizations associated with inequality. Against this national
benchmark, 17% of CCGs had significantly worse-than-benchmark equity, and 23%
significantly better. The corresponding figures were 11% and 12% respectively
against the similar populations benchmark. Deprivation-related inequality in
potentially avoidable emergency admissions varies substantially between English
CCGs serving similar populations, beyond expected statistical variation.
Administrative data on inequality in healthcare quality within similar
populations served by different healthcare organizations can provide useful
information for healthcare quality assurance.
PMID- 29335162
TI - The effectiveness of virtual simulation in improving student nurses' knowledge
and performance during patient deterioration: A pre and post test design.
AB - BACKGROUND: Preparing nursing students to perform competently in complex
emergency situations, such as during rapid patient deterioration, is challenging.
Students' active engagement in such scenarios cannot be ensured, due to the
unexpected nature of such infrequent events. Many students may consequently not
experience and integrate the management of patient deterioration into their
knowledge and practical competency by the end of their studies, making them
unprepared to manage such situations as practicing nurses. This study
investigated the effectiveness of virtual simulation in improving performance
during rapid patient deterioration. OBJECTIVE: To investigate the effectiveness
of virtual simulation in improving student nurses' knowledge and performance
during rapid patient deterioration. DESIGN: A pre- and post-test design was used.
SETTING: Nursing students at a university in Malta were invited to participate in
a virtual simulation program named FIRST2ACTWebTM, using their own computer
devices. PARTICIPANTS: A total of 166 (response rate=50%) second and third year
diploma and degree nursing students participated in the study. METHODS: The
simulation included three scenarios (Cardiac-Shock-Respiratory) portraying
deteriorating patients. Performance feedback was provided at the end of each
scenario. Students completed pre- and post-scenario knowledge tests and
performance during each scenario was recorded automatically on a database.
RESULTS: Findings showed a significant improvement in the students' post-scenario
knowledge (z=-6.506, p<0.001). Highest mean performance scores were obtained in
the last scenario (M=19.7, median: 20.0, s.d. 3.41) indicating a learning effect.
Knowledge was not a predictor of students' performance in the scenarios.
CONCLUSIONS: This study supports virtual simulation as an effective learning tool
for pre-registration nursing students in different programs. Simulation improves
both knowledge about and performance during patient deterioration. Virtual
simulation of rare events should be a key component of undergraduate nurse
education, to prepare students to manage complex situations as practicing nurses.
PMID- 29335163
TI - N,N-Diethylmethylamine as lineshape standard for NMR above 130 K.
AB - We demonstrate that N,N-Diethylmethylamine (DEMA) is a useful compound for
shimming the magnetic field when doing NMR experiments at room temperature and
130 K, near the temperature used in many dynamic nuclear polarization (DNP)
experiments. The resonance assigned to the N-methyl carbon in DEMA at 14.7 T and
140 K has a full-width-half-max linewidth of <4 Hz and has a spin-lattice
relaxation time of 0.17 +/- 0.03 s.
PMID- 29335164
TI - Local T1-T2 distribution measurements in porous media.
AB - A novel slice-selective T1-T2 measurement is proposed to measure spatially
resolved T1-T2 distributions. An adiabatic inversion pulse is employed for slice
selection. The slice-selective pulse is able to select a quasi-rectangular slice,
on the order of 1 mm, at an arbitrary position within the sample.The method does
not employ conventional selective excitation in which selective excitation is
often accomplished by rotation of the longitudinal magnetization in the slice of
interest into the transverse plane, but rather a subtraction based on CPMG data
acquired with and without adiabatic inversion slice selection. T1 weighting is
introduced during recovery from the inversion associated with slice selection.
The local T1-T2 distributions measured are of similar quality to bulk T1-T2
measurements. The new method can be employed to characterize oil-water mixtures
and other fluids in porous media. The method is beneficial when a coarse spatial
distribution of the components is of interest.
PMID- 29335165
TI - Dioxins, furans and dioxin-like PCBs in sediment samples and suspended
particulate matter from the Scheldt estuary and the North Sea Coast: Comparison
of CALUX concentration levels in historical and recent samples.
AB - BACKGROUND: The Scheldt estuary is historically a highly polluted river system.
While several studies have focused on contamination with metals, pesticides,
Polycyclic Aromatic Hydrocarbons (PAHs) and marker PolyChlorinated Biphenyls
(PCBs), no data are available concerning past contamination by dioxin-like
compounds. OBJECTIVES: The objective of this study is to determine spatial and
time trends of PolyChlorinated Dibenzo-p-Dioxins and DibenzoFurans (PCDD/Fs) and
dioxin-like PCBs (dl-PCBs) in sediment samples and Suspended Particulate Matter
(SPM) from the Scheldt River basin and the North Sea Coast. METHODS: Dioxin-like
compounds (PCDD/F and dl-PCB fractions) were measured with the CALUX-bioassay.
Bioanalytical EQuivalent concentrations (BEQs) and Total Organic Carbon (TOC)
content of historical (1982-1984) and recent (2011-2015) sediment and SPM samples
from different locations in the coastal area and the estuary, were evaluated.
RESULTS: A decrease in dioxin-like compound concentrations was found at all
stations over time, especially for the PCDD/Fs. Dl-PCBs were relatively low in
all samples. The Scheldt mouth and the Antwerp harbor yielded the highest BEQs
and levels were higher in SPM than in sediment due to the higher organic carbon
content in this fraction. CONCLUSIONS: Current PCDD/F and dl-PCB levels in the
Belgian Coastal Zone and Scheldt estuary are much lower than their levels 30
years ago and pose a relatively low risk to the aquatic system. This is the
result of a strong decrease in emissions, however, large local variabilities in
sediment concentration levels can still exist because of local variability in
sedimentation, erosion rates and in organic carbon content.
PMID- 29335166
TI - Ambient soil cation exchange capacity inversely associates with infectious and
parasitic disease risk in regional Australia.
AB - Human contact with soil may be important for building and maintaining normal
healthy immune defence mechanisms, however this idea remains untested at the
population-level. In this continent-wide, cross-sectional study we examine the
possible public health benefit of ambient exposures to soil of high cation
exchange capacity (CEC), a surrogate for potential immunomodulatory soil
microbial diversity. We compare distributions of normalized mean 2011/12-2012/13
age-standardized public hospital admission rates (cumulative incidence) for
infectious and parasitic diseases across regional Australia (representing an
average of 29,516 patients/year in 228 local government areas), within tertiles
of socioeconomic status and soil exposure. To test the significance of soil CEC,
we use probabilistic individual-level environmental exposure data (with or
without soil), and group-level variables, in robust non-parametric multilevel
modelling to predict disease rates in unseen groups. Our results show that in
socioeconomically-deprived areas with high CEC soils, rates of infectious and
parasitic disease are significantly lower than areas with low CEC soils. Also,
health inequality (relative risk) due to socioeconomic status is significantly
lower in areas with high CEC soils compared to low CEC soils (Delta relative risk
= 0.47; 95% CI: 0.13, 0.82). Including soil exposure when modelling rates of
infectious and parasitic disease significantly improves prediction performance,
explaining an additional 7.5% (Delta r2 = 0.075; 95% CI: 0.05, 0.10) of variation
in disease risk, in local government areas that were not used for model building.
Our findings suggest that exposure to high CEC soils (typically high soil
biodiversity) associates with reduced risk of infectious and parasitic diseases,
particularly in lower socioeconomic areas.
PMID- 29335167
TI - Fate and hazard of the electrochemical oxidation of triclosan. Evaluation of
polychlorodibenzo-p-dioxins and polychlorodibenzofurans (PCDD/Fs) formation.
AB - Triclosan (TCS) is widely used as antiseptic or preservative in many personal
care products (PCPs), such as cosmetics, hand wash, toothpaste and deodorant
soaps, among others. It is characterized by acute toxicity, resistance to
biodegradation, environmental persistence and relatively high lipophilicity. In
order to protect the environment and natural resources from the negative effects
of the discharge of polluted wastewater with TCS, the application of efficient
remediation technologies able to degrade the pollutant to harmless levels becomes
crucial. Electrochemical oxidation, among all advanced oxidation processes
(AOPs), has been reported as very effective in the complete degradation of a
number of persistent pollutants; therefore, its performance using boron-doped
diamond (BDD) anodes, and response to operation variables, has been studied in
this work. As expected, complete degradation of TCS was achieved in all the
studied conditions; however, going a step further and knowing that TCS is a
precursor of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), their
quantitative presence in the oxidation media has been assessed. Results showed
the dominance of dichlorinated (DCDD) and trichlorinated (TrCDD/Fs) in the
homologue profile of total PCDD/Fs, reaching values up to 1.48 * 105 pg L-1 in
samples with initial concentration of TCS of 100 mg L-1 and NaCl as electrolyte.
Under these conditions, the International Toxicity Equivalency Factor (I-TEF)
achieved values up to 2.76 * 102 pg L-1. Nevertheless, the presence of copper in
the oxidation medium tends to reduce I-TEF values. Finally, considering the
information reported in literature, a mechanism describing the formation of low
chlorinated PCDD/Fs from TCS oxidation reactions is proposed.
PMID- 29335168
TI - WRF modeling of PM2.5 remediation by SALSCS and its clean air flow over Beijing
terrain.
AB - Atmospheric simulations were carried out over the terrain of entire Beijing,
China, to investigate the effectiveness of an air-pollution cleaning system named
Solar-Assisted Large-Scale Cleaning System (SALSCS) for PM2.5 mitigation by using
the Weather Research and Forecasting (WRF) model. SALSCS was proposed to utilize
solar energy to generate airflow therefrom the airborne particulate pollution of
atmosphere was separated by filtration elements. Our model used a derived
tendency term in the potential temperature equation to simulate the buoyancy
effect of SALSCS created with solar radiation on its nearby atmosphere. PM2.5
pollutant and SALSCS clean air were simulated in the model domain by passive
tracer scalars. Simulation conditions with two system flow rates of 2.64 * 105
m3/s and 3.80 * 105 m3/s were tested for seven air pollution episodes of Beijing
during the winters of 2015-2017. The numerical results showed that with eight
SALSCSs installed along the 6th Ring Road of the city, 11.2% and 14.6% of PM2.5
concentrations were reduced under the two flow-rate simulation conditions,
respectively.
PMID- 29335169
TI - Seasonal variations in fine particle composition from Beijing prompt oxidative
stress response in mouse lung and liver.
AB - Exposure to air pollution can induce oxidative stress, inflammation and adverse
health effects. To understand how seasonal and chemical variations drive health
impacts, we investigated indications for oxidative stress and inflammation in
mice exposed to water and organic extracts from urban fine particles/PM2.5
(particles with aerodynamic diameter <= 2.5 MUm) collected in Beijing, China.
Higher levels of pollution components were detected in heating season (HS, winter
and part of spring) PM2.5 than in the non-heating season (NHS, summer and part of
spring and autumn) PM2.5. HS samples were high in metals for the water extraction
and high in polycyclic aromatic hydrocarbons (PAHs) for the organic extraction
compared to their controls. An increased inflammatory response was detected in
the lung and liver following exposure to the organic extracts compared to the
water extracts, and mostly in the HS PM2.5. While reduced antioxidant response
was observed in the lung, it was activated in the liver, again, more in the HS
extracts. Nrf2 transcription factor, a master regulator of stress response that
controls the basal oxidative capacity and induces the expression of antioxidant
response, and its related genes were induced. In the liver, elevated levels of
lipid peroxidation adducts were measured, correlated with histologic analysis
that revealed morphologic features of cell damage and proliferation, indicating
oxidative and toxic damage. In addition, expression of genes related to
detoxification of PAHs was observed. Altogether, the study suggests that the
acute effects of PM2.5 can vary seasonally with stronger health effects in the HS
than in the NHS in Beijing, China and that some secondary organs may be
susceptible for the exposure damage. Specifically, the liver is a potential organ
influenced by exposure to organic components such as PAHs from coal or biomass
burning and heating.
PMID- 29335170
TI - Risk factors associated with rural water supply failure: A 30-year retrospective
study of handpumps on the south coast of Kenya.
AB - An improved understanding of failure risks for water supplies in rural sub
Saharan Africa will be critical to achieving the global goal of safe water for
all by 2030. In the absence of longitudinal biophysical and operational data,
investigations into water point failure risk factors have to date been limited to
cross-sectional research designs. This retrospective cohort study applies
survival analysis to identify factors that predict failure risks for handpumps
installed on boreholes along the south coast of Kenya from the 1980s. The
analysis is based on a unique dataset linking attributes of >300 water points at
the time of installation with their operational lifespan over the following
decades. Cox proportional hazards and accelerated failure time models suggest
water point failure risks are higher and lifespans are shorter when water
supplied is more saline, static water level is deeper, and groundwater is pumped
from an unconsolidated sand aquifer. The risk of failure also appears to grow as
distance to spare part suppliers increases. To bolster the sustainability of
rural water services and ensure no community is left behind, post-construction
support mechanisms will need to mitigate heterogeneous environmental and
geographical challenges. Further studies are needed to better understand the
causal pathways that underlie these risk factors in order to inform policies and
practices that ensure water services are sustained even where unfavourable
conditions prevail.
PMID- 29335172
TI - Preparation of amidoxime-functionalized mesoporous silica nanospheres (ami-MSN)
from coal fly ash for the removal of U(VI).
AB - It is usually difficult to control the microstructure of mesoporous silica
materials using coal fly ash as raw materials. In this study, amidoxime
functionalized mesoporous silica nanospheres (ami-MSN) were prepared from coal
fly ash using a novel interfacial cohydrolysis-condensation method in an alkane
aqueous system. Characterizations suggested a regular microstructure, high
specific surface area (676 m2/g) as well as stable and uniformly distributed
amidoxime groups in the ami-MSN framework. Furthermore, ami-MSN displays a high
U(VI) removal capacity in sorption experiments (98.9% removal efficiency of 50
ppm U(VI) at a dosage of 600 mg/L). The sorption showed significant pH
dependence. Introducing various cations and anions showed differing effects on
sorption, which can be attributed to differing complexation abilities of ions/ami
MSN/U(VI). The sorption mechanism was also studied. In pursuit of the strategy of
"treating wastewater with materials derived from waste," this work suggests that
ami-MSN can be an effective and low-cost sorbent for U(VI) removal.
PMID- 29335171
TI - Effect of hydrogen peroxide on Microcystic aeruginosa: Role of cytochromes P450.
AB - Cyanobacterial bloom has been rising as a worldwide issue owing to its adverse
effects to water quality and ecological health. To solve this problem, hydrogen
peroxide (H2O2) has been considered as a potential algaecide because no by
products are generated after treatment and because it kills cyanobacteria
selectively. In addition, cytochromes P450 (CYPs) was reported to be related with
H2O2, but the roles of CYPs in the regulation of H2O2 in cyanobacteria have yet
to be investigated. In this study, the CYPs suicide inhibitor 1
aminobenzotriazole (ABT) was added to the representative cyanobacteria
Microcystis aeruginosa (M. aeruginosa) exposed to H2O2. The results showed that
CYPs mediates the effects of H2O2 on M. aeruginosa. To be exact, the addition of
ABT induced greater inhibitory effects on the growth and higher reactive oxygen
species levels in M. aeruginosa comparing to those treated with H2O2 alone. At
the same time, photosynthetic parameters significantly decreased, and the content
of extracellular microcystins (MCs) increased but the total MCs decreased due to
the combined effect of H2O2 and ABT. ABT also intensified the aggregation of Fe,
which might explain the effects on photosynthesis and synthesis of MCs.
Furthermore, the transcriptional levels of MCs-synthesis genes (mcyA and mcyD)
decreased but MCs-release gene (mcyH) increased, and photosynthetic genes (psaB,
psbD1 and rbcL) decreased, which confirmed the effects on the MC
production/release and electron transport of photosynthesis, respectively. In
summary, this study illuminated the mediation role of CYPs in the adverse effects
on M. aeruginosa induced by H2O2, thus providing new theoretical basis for the
explanation of H2O2 as potential algaecide.
PMID- 29335173
TI - Application of Fe3O4@MIL-100 (Fe) core-shell magnetic microspheres for evaluating
the sorption of organophosphate esters to dissolved organic matter (DOM).
AB - Organophosphate esters (OPEs) are widely used as flame retardants and
plasticizers in many products and materials. Because of the potential biologic
toxicity on human beings, OPEs are regarded as a class of emerging pollutants.
Dissolved organic matters (DOM) have significant effects on the bioavailability
and toxicity of the pollutants in the environment. Negligible-depletion solid
phase microextraction (nd-SPME) is an efficient way for measuring the freely
dissolved pollutants but suffers from long equilibrium time. Metal-organic
frameworks (MOFs) are a class of porous crystalline materials with unique
properties such as high pore volume, regular porosity, and tunable pore size,
being widely used for the extraction of various organic compounds. Here we
developed a novel method for quick determination the sorption coefficients of
OPEs to DOM in aquatic phase using Fe3O4@MIL-100 (Fe) core-shell magnetic
microspheres. The mesoporous structures of the as-synthesized microspheres
hindered the extraction of OPEs which associated with humic acid due to the
volume exclusion effect. However, the freely dissolved OPEs can access into the
mesoporous and then were extracted by MIL-100 (Fe). Due to the small pore size
(4.81 nm), large surface area (141 m2 g-1), high pore volume (0.17 g3 g-1), and
ultra-thin MOFs layers, Fe3O4@MIL-100 (Fe) core-shell magnetic microspheres have
large contact area for the analytes in aqueous phase and therefore the diffusion
distance was largely shortened. Besides, the microspheres can be collected
conveniently after the extraction process by applying a magnetic field. Compared
to the nd-SPME method with 35 h equilibration time (t90%), the proposed method
for these studied OPEs only need 24 min to achieve equilibration. The sorption
coefficients (logKDOC) of the OPEs to humic acid were ranged from 3.84-5.28,
which were highly consistent with the results by using polyacrylate-coated fiber
and polydimethylsiloxane-coated fiber with nd-SPME.
PMID- 29335174
TI - Testing association between soil bacterial diversity and soil carbon storage on
the Loess Plateau.
AB - Bacteria are widely distributed and play an important role in soil carbon (C)
cycling. The impact of soil bacterial diversity on soil C storage has been well
established, yet little is known about the underlying mechanisms and the
interactions among them. Here, we examined the association between soil bacterial
diversity and soil C storage in relation to vegetation restoration on the Loess
Plateau. The dominant phyla among land use types (artificial forest, Af; natural
shrubland, Ns; artificial grassland, Ag; natural grassland, Ng; slope cropland,
Sc) were Acidobacteria, Actinobacteria, Alphaproteobacteria, and
Betaproteobacteria, which transited from Acidobacteria-dominant to Actinobacteria
dominant community due to vegetation restoration. Soil C storage and the Shannon
diversity index of soil bacterial community (HBacteria) showed the order Ns > Ng
> Af > Ag > Sc, whereas no significant difference was found in Good's coverage (p
> .05). Further, a strong relationship was observed between the relative
abundance of dominant bacterial groups and soil C storage (p < .05).
Additionally, soil bacterial diversity was closely related to soil C storage
based on the structural equation model (SEM) and generalized additive models
(GAMs). Specifically, soil C storage had the largest deterministic effects,
explaining >70% of the variation and suggesting a strong association between soil
C storage and soil bacterial diversity. Overall, we propose that further studies
are necessary with a focus on the soil bacterial groups with specific functions
in relation to soil C storage on the Loess Plateau.
PMID- 29335175
TI - An assessment of the Ca weathering sources to surface waters on the Precambrian
Shield in central Ontario.
AB - There is increasing concern over the negative ecological impacts caused by
falling calcium (Ca) concentrations in lakes, particularly in central Ontario,
Canada. Forecasting regional changes in lake Ca concentrations relies on accurate
estimates of mineral weathering rates that are not widely available. In this
study, bulk atmospheric deposition, surface water and soil chemistry along with
87Sr/86Sr isotope measurements were used to provide regional insight into
weathering controls on Ca concentrations in lakes. Regionally, Ca concentrations
in 90% of 129 lakes sampled in central Ontario were <0.1 mmol L-1 and the Ca/Sr
ratio in lakes increased and the K/Sr ratio decreased with increasing Sr
concentration, which is indicative of greater Ca sources from calcite or apatite
in the higher Ca lakes. Significant relationships between 87Sr/86Sr ratios and
Ca/Sr rations in dilute acid (0.1 M HCl) soil extracts are also indicative of the
presence of trace amounts of calcite or apatite in surficial soils. Within the
low (<0.7 mmol L-1) Ca lakes, defined in this study that are considered most at
risk from falling Ca concentrations, 87Sr/86Sr ratios fell within the range
observed in weak acid soil extracts and were also significantly related to Ca/Na
and K/Sr ratios in surface waters. There were large inconsistencies however,
between Ca/Na ratios and Ca/Sr in surface waters and soil acid extracts that
suggest differences in 87Sr/86Sr ratios in surface waters of the low Ca lakes do
not simply reflect differences in Ca derived from non-silicate minerals in
surficial soils and that that Ca sources from deeper soil or bedrock are also
important contributors to surface water Ca in these low Ca lakes.
PMID- 29335176
TI - Arsenic characteristics in the terrestrial environment in the vicinity of the
Shimen realgar mine, China.
AB - In this study, multiple types of samples, including soils, plants, litter and
soil invertebrates, were collected from a former arsenic (As) mine in China. The
total As concentrations in the soils, earthworms, litter and the aboveground
portions of grass from the contaminated area followed the decreasing order of 83
2224 mg/kg, 31-430 mg/kg, 1-62 mg/kg and 2-23 mg/kg, respectively. X-ray
absorption near-edge structure (XANES) analysis revealed that the predominant
form of As in the soils was arsenate (As(V)), while no arsenite (As(III)) was
detected. In the grass and litter of the native plant community, inorganic As
species (As(V) and As(III)) were the main species, while minor amounts of DMA,
MMA, AsC, and an unknown As species were also detected in the extracts analyzed
with high-performance liquid chromatography inductively coupled plasma mass
spectrometry (HPLC-ICP-MS). The As speciation and As concentrations varied with
the plant species, and very high As levels (197-584 mg/kg) and proportions of
inorganic As (>99%) were found in two As-hyperaccumulating ferns, Pteris vittata
and Pteris cretica. The major As species extracted from earthworms were
inorganic, with proportions of 51-53% As(III) and 38-48% As(V). AsB was the only
organic species present in the earthworm samples, although at low proportions
(<8.99%). The internal bioconversion of other As species is hypothesized to
contribute greatly to the formation and accumulation of AsB in earthworms,
although the direct external absorption of organic As from soils might be another
source. This study sheds light on the potential sources of complex
organoarsenicals, such as AsB, in terrestrial organisms.
PMID- 29335177
TI - Study of the evolution of gravel beaches nourished with sand.
AB - Coastal erosion is a worldwide problem, so accurate knowledge of the factors
involved in the shoreline evolution is of great importance. This study analysed
three gravel beaches that were nourished with sand from the same source. However,
the evolution of their shoreline was different in each case. For its analysis,
different factors were studied such as the shoreline and cross-shore profile
evolution, the maritime climate, sedimentology and mineralogy. From the results,
it should be noted that Centro beach is the most stable with a loss of surface
after the first regeneration of 12.8%, while Carrer de mar is the most instable
with a loss of 20.9%. The Posidonia oceanica meadow is one of the factors that
make Centro beach the most stable despite being the one that receives the most
wave energy. Another factor is its mineralogy and more specifically the
composition of the particles that form the sample. Thus, it is observed how the
cracking or the formation of particles by different minerals with a fragile
union, are factors that make the beaches behave differently against erosion. For
this reason, it is concluded that in order for the shoreline to be as stable as
possible over time, a previous study of the sediment to be used for nourishment
is necessary, as well as its possible effect on the ecosystem, since the future
shoreline evolution will depend on it.
PMID- 29335178
TI - Bone lead levels in an environmentally exposed elderly population in shanghai,
China.
AB - This study looked at measurements of lead (Pb) in a pilot population of
environmentally exposed elderly residents of Shanghai, China and presented the
first set of bone Pb data on an elderly Chinese population. We found that with
environmental exposures in this population using K-shell x-ray fluorescence
(KXRF) bone Pb measurements 40% of the individuals had bone Pb levels above the
nominal detection limit with an average bone lead level of 4.9 +/- 3.6 MUg/g.
This bone lead level is lower than comparable values from previous studies of
community dwelling adults in US cities. This population had a slightly higher
geometric mean blood Pb of 2.6 MUg/dL than the adult US population. The main
conclusion of this data is that in Shanghai there is environmental exposure to
Pb, measured through blood and bone, which should be further investigated to
assess the health impact of this exposure.
PMID- 29335179
TI - Chronic nitrogen addition induces a cascade of plant community responses with
both seasonal and progressive dynamics.
AB - Short-lived herbaceous plants provide a useful model to rapidly reveal how
multiple generations of plants in natural plant communities of sensitive desert
ecosystems will be affected by N deposition. We monitored dynamic responses of
community structure, richness, evenness, density and biomass of herbaceous plants
to experimental N addition (2:1 NH4+:NO3- added at 0, 0.5, 1, 3, 6 and 24gNm-2a
1) in three seasons in each of three years in the Gurbantunggut desert, a typical
temperate desert of central Asia. We found clear rate-dependent and season
dependent effects of N deposition on each of these variables, in most cases
becoming more obvious through time. N addition reduced plant richness, leading to
a loss of about half of the species after three generations in the highest N
application level. Evenness and density were relatively insensitive to all but
the greatest levels of N addition for two generations, but negative effects
emerged in the third generation. Biomass, both above and below ground, was non
linearly affected by N deposition. Low and intermediate levels of N deposition
often increased biomass, whereas the highest level suppressed biomass.
Stimulatory effects of intermediate N addition disappeared in the third
generation. All of these responses are strongly interrelated in a cascade of
changes. Notably, changes in biomass due to N deposition were mediated by
declines in richness and evenness, and other changes in community structure,
rather than solely being the direct outcome of release from limitation. The
interrelationships between N deposition and the different plant community
attributes change not only seasonally, but also progressively change through
time. These temporal changes appear to be largely independent of interannual or
seasonal climatic conditions.
PMID- 29335180
TI - Synthesis of nanometer-sized fayalite and magnesium-iron(II) mixture olivines.
AB - Olivines are divalent orthosilicates with important geologic, biological, and
industrial significance and are typically comprised of mixtures of Mg2+ and Fe2+
ranging from forsterite (Mg2SiO4) to fayalite (Fe2SiO4). Investigating the role
of Fe(II) in olivine reactivity requires the ability to synthesize olivines that
are nanometer-sized, have different percentages of Mg2+ and Fe2+, and have good
bulk and surface purity. This article demonstrates a new method for synthesizing
nanosized fayalite and Mg-Fe mixture olivines.First, carbonaceous precursors are
generated from sucrose, PVA, colloidal silica, Mg2+, and Fe3+. Second, these
precursors are calcined in air to burn carbon and create mixtures of Fe(III)
oxides, forsterite, and SiO2. Finally, calcination in reducing CO-CO2 gas buffer
leads to Fe(II)-rich olivines. XRD, Mossbauer, and IR analyses verify good bulk
purity and composition. XPS indicates that surface iron is in its reduced Fe(II)
form, and surface Si is consistent with olivine. SEM shows particle sizes
predominately between 50 and 450 nm, and BET surface areas are 2.8-4.2 m2/g. STEM
HAADF analysis demonstrates even distributions of Mg and Fe among the available
M1 and M2 sites of the olivine crystals. These nanosized Fe(II)-rich olivines are
suitable for laboratory studies with in situ probes that require mineral samples
with high reactivity at short timescales.
PMID- 29335181
TI - Enhancing the photovoltaic performance of bulk heterojunction polymer solar cells
by adding Rhodamine B laser dye as co-sensitizer.
AB - Ternary blend (TB) strategy has been considered as an effective method to enhance
the photovoltaic performance of bulk heterojunction (BHJ) polymer solar cells
(PSCs). Here, we report on TB-based PSCs containing two donor materials; poly-3
hexylthiophene (P3HT) and Rhodamine B (RhB) laser organic dye, and [6,6]-phenyl
C61 butyric acid methyl ester (PC61BM) as an acceptor. The influence of RhB
weight percentage and injection volume was extensively studied. To gain insight
into the influences of RhB on the photovoltaic performance of PSCs,
physicochemical and optical properties of TBs were compared with those of BHJ
binary blend as a standard. RhB broadened the light absorption properties of the
active layer and played a bridging role between P3HT and PC61BM. The PCE and
short-circuit current density (Jsc) of the optimized TB-based PSCs comprising of
0.5 wt% RhB reached 5% and 12.12 mA/cm2, respectively. Compared to BHJ standard
cell, the PCE and the generated current was improved by two orders of magnitude
due to higher photon harvest of the active layer, cascade energy level structure
of TB components and a considerable decrease in the charge carrier recombination.
The results suggest that RhB can be considered as an effective material for
application in PSCs to attain high photovoltaic performance.
PMID- 29335182
TI - Microstructures and performances of pegylated polysulfone membranes from an in
situ synthesized solution via vapor induced phase separation approach.
AB - In situ pegylated (PEGylated) microporous membranes have been extensively
reported using poly(ethylene glycol) (PEG)-based polymers as blending additives.
Alternatively, free standing PEGylated polysulfone (PSf) membranes with excellent
hydrophilicity and antifouling ability were directly fabricated from
polysulfone/poly(ethylene glycol) methyl ether methacrylate (PSf/PEGMA) solutions
after in situ cross-linking polymerization without any treatment via vapor
induced phase separation (VIPS) process for the first time. The microstructures
and performances of the resulting membranes shifted regularly by adjusting
exposure time of the liquid film in humid air. With increasing exposure time,
plenty of worm-like networks formed and distributed on membrane surfaces,
meanwhile cross-sectional morphology changed from asymmetric finger-like
microporous structure to symmetric cellular-like structure, resulting in better
mechanical stability. As the exposure time raised from 0 to 5 min, the surface
coverage of carboxyl groups increased from ~1.1 to 4.0 mol%, leading to the
decrease in water contact angle from ~63 to 27 degrees and the increase in water
flux from ~110 to 512 L m-2 h-1. In addition, at prolonged exposure time,
increasing hydrophilic PEG chains migrated to membrane surfaced and repelled the
adsorption and deposition of protein, resulting in better antifouling ability.
The findings of this study offer a facile and high efficient strategy for
flexible design and fabrication of the in situ PEGylated membranes with desirable
structures and performances in large scale.
PMID- 29335183
TI - Microwave-assisted synthesis of palladium nanoparticles intercalated nitrogen
doped reduced graphene oxide and their electrocatalytic activity for direct
ethanol fuel cells.
AB - Palladium nanoparticles decorated reduced graphene oxide (Pd-rGO) and palladium
nanoparticles intercalated inside nitrogen doped reduced graphene oxide (Pd-NrGO)
hybrids have been synthesized by applying a very simple, fast and economic route
using microwave-assisted in-situ reduction and exfoliation method. The Pd-NrGO
hybrids materials show good activity as catalyst for ethanol electro oxidation
for direct ethanol fuel cells (DEFCs) as compared to Pd-rGO hybrids. The enhanced
direct ethanol fuel cell can serve as alternative to fossil fuels because it is
renewable and environmentally-friendly with a high energy conversion efficiency
and low pollutant emission. As proof of concept, the electrocatalytic activity of
Pd-NrGO hybrid material was accessed by cyclic voltammetry in presence of ethanol
to evaluate its applicability in direct-ethanol fuel cells (DEFCs). The Pd-NrGO
catalyst presented higher electro active surface area (~6.3 m2 g-1) for ethanol
electro-oxidation when compared to Pd-rGO hybrids (~3.7 m2 g-1). Despite the
smaller catalytic activity of Pd-NrGO, which was attributed to the lower
exfoliation rate of this material in relation to the Pd-rGO, Pd-NrGO showed to be
very promising and its catalytic activity can be further improved by tuning the
synthesis parameters to increase the exfoliation rate.
PMID- 29335184
TI - Trimellitated sugarcane bagasse: A versatile adsorbent for removal of cationic
dyes from aqueous solution. Part I: Batch adsorption in a monocomponent system.
AB - Trimellitated-sugarcane bagasse (STA) was used as an environmentally friendly
adsorbent for removal of the basic dyes auramine-O (AO) and safranin-T (ST) from
aqueous solutions at pH 4.5 and 7.0. Dye adsorption was evaluated as a function
of STA dosage, agitation speed, solution pH, contact time, and initial dye
concentration. Pseudo-first- and pseudo-second-order, Elovich, intraparticle
diffusion, and Boyd models were used to model adsorption kinetics. Langmuir,
Dubinin-Radushkevich, Redlich-Peterson, Sips, Hill-de Boer, and Fowler-Guggenheim
models were used to model adsorption isotherms, while a Scatchard plot was used
to evaluate the existence of different adsorption sites. Maximum adsorption
capacities for removal of AO and ST were 1.005 and 0.638 mmol g-1 at pH 4.5, and
1.734 and 1.230 mmol g-1 at pH 7.0, respectively. Adsorption enthalpy changes
obtained by isothermal titration calorimetry (ITC) ranged from -21.07 +/- 0.25 to
-7.19 +/- 0.05 kJ mol-1, indicating that both dyes interacted with STA by
physisorption. Dye desorption efficiencies ranged from 41 to 51%, and re
adsorption efficiencies ranged from 66 to 87%, showing that STA can be reused in
new adsorption cycles. ITC data combined with isotherm studies allowed
clarification of adsorption interactions.
PMID- 29335185
TI - One step electrochemical route to the fabrication of highly ordered array of
cylindrical nano porous structure and its electrocatalytic performance toward
efficient hydrogen evolution.
AB - An efficient and non-precious metal catalyst is a key factor for hydrogen
evolution reaction (HER). Here we report that the fabrication of highly ordered
porous arrays of Cu-Zn-Ni alloy has been carried out in a one-step
electrochemical route at a constant apparent current density of -3 A.cm-2. The
optimum film composition and reactivity of the electrodes for catalytic hydrogen
evolution reaction were analyzed by using different current densities, deposition
time and bath concentration. For this purpose, onset potentials in linear sweep
voltammograms (LSV) were compared. The structure and morphology of nanoporous Cu
Zn-Ni and Cu-Zn alloy were characterized by SEM and energy dispersive X-ray (EDS)
analysis. The experimental results on the behavior of electrocatalytic activity
of prepared alloys showed that the addition of nickel to the alloys improves of
the electrocatalytic performance of the electrodes toward HER. In addition,
enhancement of electrochemical activity toward hydrogen evolution can be
attributed to the large electrochemical active surface area and porous structure
of Cu-Zn-Ni alloy. In order to improvement of reaction kinetics, Tafel plots were
derived from LSV voltammograms, and the exchange current densities for HER on
synthesized electrodes (Cu-Zn and Cu-Zn-Ni alloys) were calculated about 3.2 * 10
5 and 2.1 * 10-3 mA.cm-2, respectively.
PMID- 29335186
TI - Rheological and calorimetric study of alkyltrimethylammonium bromide-sodium
salicylate wormlike micelles in aqueous binary systems.
AB - HYPOTHESIS: It is known that additives like glycerol and sucrose lead to the
swelling of aqueous bilayer Lalpha phases. The swelling of the Lalpha phases can
be explained by the increase of the refractive index of the mixed solvent, which
lowers the van der Waals attraction between the bilayers. Afterwards, the
undulation forces between the bilayers can push them apart. This hypothesis was
previously extended to wormlike micelles (WLM) of cetyltrimethylammonium bromide
(CTAB) and sodium salicylate (NaSal). These types of self-assembly structures
have viscoelastic properties, and the zero shear viscosity of these solutions is
dependent on the molar ratio NaSal/CTAB, R. At R = 0.6, R = 1.0 and R ~ 2.6 the
viscosity goes, respectively, through a maximum, a minimum and another maximum.
These viscosities can be explained by differences in relaxation mechanisms
predominant in each region. Similarly to what is observed to bilayer Lalpha
phases, the additives would change the interaction between the WLM, affecting the
relaxation processes of each region, altering the profile from two maxima and one
minimum to a single maximum in viscosity. In the present manuscript, it is
investigated whether it is only the refractive index, other solvent properties,
or a combination of several factors that induce these changes in WLM. For this,
several additives, forming binary mixtures with water, were studied, through
rheology of CTAB/NaSal and calorimetry of tetradecyltrimethylammonium bromide
(TTAB)/NaSal. EXPERIMENTS: Herein, we present the zero-shear viscosity diagrams
of NaSal and CTAB with glycerol, sucrose, dimethyl sulfoxide, 1,3-butanediol and
urea combined with water. Additionally, isothermal titration calorimetry was used
to obtain the variations of enthalpy for formation of WLM of TTAB and NaSal in
mixtures of water and such additives. FINDINGS: Based on our data, only the
refractive index match is not enough to explain the rheological and calorimetric
behaviors of the WLM. For instance, sucrose has little effect on the micelles,
even at the same refractive index match conditions. Additional characteristics,
such as dielectric constant, the cohesivity of the solvent (here symbolized by
the Gordon parameter), and the interactions of the additive with the micelles,
have to be considered to better describe the results.
PMID- 29335187
TI - Novel low-fouling membranes from lab to pilot application in textile wastewater
treatment.
AB - A novel antifouling coating based on the polymerization of a polymerisable
bicontinuous microemulsion (PBM) was developed and applied for commercially
available membranes for textile wastewater treatment. PBM coating was produced by
polymerizing, on a polyethersulfone (PES) membrane, a bicontinuous microemulsion,
realized by finely tuning its properties in terms of chemical composition and
polymerization temperature. In particular, the PBM was prepared by using, as the
surfactant component, inexpensive and commercially available
dodecyltrimethylammonium bromide (DTAB). The coating exhibited a more hydrophilic
and a smoother surface in comparison to uncoated PES surface, making the produced
PBM membranes more resistant and less prone to be affected by fouling. The anti
fouling potential of PBM membranes was assessed by using humic acid (HA) as a
model foulant, evaluating the water permeability decrease as an indicator of the
fouling propensity of the membranes. PBM membrane performances in terms of dye
rejection, when applied for model textile wastewater treatment, were also
evaluated and compared to PES commercial ones. The PBM membranes were finally
successfully scaled-up (total membrane area 0.33 m2) and applied in a pilot
membrane bioreactor (MBR) unit for the treatment of real textile wastewater.
PMID- 29335189
TI - Biofuel production and phycoremediation by Chlorella sp. ISTLA1 isolated from
landfill site.
AB - The present study aims to investigate the biofuel production ability and
potential of heavy metal remediation of Chlorella sp. ISTLA1 isolated from a
landfill site. The strain was cultured in Bold's Basal medium at different
concentration of NaHCO3 and pH. Response surface methodology was employed for the
optimization of nutrient sources for higher lipid production. Under the optimized
conditions, the yield of lipid and biomass was 365.42 and 833.14 mg L-1
respectively. GC-MS analysis of lipid indicated the presence of C8 to C31 organic
compounds consisting mainly of palmitic acid (C16:0), stearic acid (C18:0) and
oleic acid (C18:1). Additionally, remediation of heavy metals like Zn, Cu, Mn and
Fe from waste water was observed by AAS and EDX. The removal efficiency was 82.6%
for Zn, 56.5% for Cu, 79.8% for Mn and 40% for Fe. The study revealed
simultaneous biodiesel production and waste water treatment by Chlorella sp.
ISTLA1.
PMID- 29335188
TI - Electrophoretic deposition of single-source precursors as a general approach for
the formation of hybrid nanorod array heterostructures.
AB - HYPOTHESIS: Subjecting colloids to electric fields often results in
(electrophoretic) deposition on conductive substrates. Dispersing a single-source
precursor (SSP) of choice in an appropriate solvent, should allow its deposition
on different substrates. The SSP-solvent interaction might play a role in the
deposition (e.g., direction, rate, coverage). After thermal decomposition, the
SSPs convert to the designed material, thus allowing formation of thin films or
hybrid nanostructures. EXPERIMENTS: Electrophoretic deposition (EPD) was applied
on two representative SSPs in different solvents. These SSPs were deposited onto
substrates covered with vertically-aligned ZnO nanorod (NR) arrays. After thermal
decomposition, hybrid nanostructures were obtained and their morphology and
interfaces were characterized by electron microscopy, X-ray diffraction, UV-vis,
and electrochemistry. FINDINGS: Tuning the organic dispersant-SSP interaction
allows control over the final film morphology, which can result in coating and
filling of NRs with metal-sulfides or metal-oxides after thermal decomposition of
the SSP. These findings introduce a new facile method for a fast and large-scale
uniform deposition of different (nanostructured) thin film semiconductors on a
variety of substrates. We discuss the influence of the dispersant medium on the
deposition of metallo-organic SSPs. As an example, the formed ZnO-CdS interface
supports charge transfer upon illumination.
PMID- 29335190
TI - Phytochemistry and pharmacology of the genus Leonurus: The herb to benefit the
mothers and more.
AB - Plants belonging to the genus Leonurus, also named motherwort, are traditionally
used for anti-gynecological disorder in East Asia, and for sedative in Europe.
Chemical investigation of the genus Leonurus not only enriched the natural
products library, but also enlarged the pharmacological application of this
traditional herb. In this review, we systematically summarized the structures of
259 compounds isolated from the genus Leonurus, featured with 147 labdane
diterpenoids. The reported bioactivity studies up to 2017 are presented in the
second part, with the main focus on the isolated compounds and also concerning
the extracts. In addition to the traditional uterine contraction and sedative
activity, recently the cardiovascular protection effect of leonurine has drawn
most attention. Other than that, neuroprotection, anti-inflammation, anti-cancer,
anti-platelet aggregation and many other activities have been assigned to various
compounds from the genus Leonurus. Among 70 bioactivity references cited in this
review, 57% of them were concentrated on two alkaloids (leonurine and
stachydrine), whereas only 20% are about the 147 diterpenoids. Anti-inflammation
is the major bioactivity discovered so far for the labdane diterpenoids from the
genus Leonurus, whose further therapeutic potential still remains for
exploration.
PMID- 29335191
TI - Effects of alumina nanoparticles on the microstructure, strength and wear
resistance of poly(methyl methacrylate)-based nanocomposites prepared by friction
stir processing.
AB - In this study, alumina-reinforced poly(methyl methacrylate) nanocomposites
(PMMA/Al2O3) containing up to 20vol% nanoparticles with an average diameter of
50nm were prepared by friction stir processing. The effects of nanoparticle
volume fraction on the microstructural features and mechanical properties of PMMA
were studied. It is shown that by using a frustum pin tool and employing an
appropriate processing condition, i.e. a rotational speed of 1600rpm/min and
transverse velocity of 120mm/min, defect free nanocomposites at microscale with
fine distribution of the nanoparticles can successfully been prepared. Mechanical
evaluations including tensile, flexural, hardness and impact tests indicate that
the strength and toughness of the material gradually increases with the
nanoparticle concentration and reach to a flexural strength of 129MPa, hardness
of 101 Shore D, and impact energy 2kJ/m2 for the nanocomposite containing 20vol%
alumina. These values are about 10% and 20% better than untreated and FSP-treated
PMMA (without alumina addition). Fractographic studies indicate typical brittle
features with crack deflection around the nanoparticles. More interestingly, the
sliding wear rate in a pin-on-disk configuration and the friction coefficient are
reduced up to 50% by addition of alumina nanoparticles. The worn surfaces exhibit
typical sliding and ploughing features.
PMID- 29335192
TI - Isolated and modulated effects of topology and material type on the mechanical
properties of additively manufactured porous biomaterials.
AB - In this study, we tried to quantify the isolated and modulated effects of
topological design and material type on the mechanical properties of AM porous
biomaterials. Towards this aim, we assembled a large dataset comprising the
mechanical properties of AM porous biomaterials with different topological
designs (i.e. different unit cell types and relative densities) and material
types. Porous structures were additively manufactured from Co-Cr using a
selective laser melting (SLM) machine and tested under quasi-static compression.
The normalized mechanical properties obtained from those structures were compared
with mechanical properties available from our previous studies for porous
structures made from Ti-6Al-4V and pure titanium as well as with analytical
solutions. The normalized values of elastic modulus and yield stress were found
to be relatively close to each other as well as in agreement with analytical
solutions regardless of material type. However, the material type was found to
systematically affect the mechanical properties of AM porous biomaterials in
general and the post-elastic/post-yield range (plateau stress and energy
absorption capacity) in particular. To put this in perspective, topological
design could cause up to 10-fold difference in the mechanical properties of AM
porous biomaterials while up to 2-fold difference was observed as a consequence
of changing the material type.
PMID- 29335193
TI - Damage mechanisms in bioactive glass matrix composites under uniaxial
compression.
AB - The damage and crack resistance improvement of bioactive glass is of prime
importance, particularly when applied to the repair of load-bearing bones. The
present contribution is focused on the prediction of damage mechanisms and crack
resistance under uniaxial compression of bioactive glass matrix composites
reinforced with a particulate phase. In order to characterize the effects of
voids and particles on the damage mechanisms and the macro-response, a two-step
homogenization is performed by considering the two phases existing at two
different scales: micro/meso through the homogenization of the porous matrix and
then meso/macro through the periodic micro-field approach. The damage in the
bioactive glass matrix is computed via an anisotropic stress-based damage model,
implemented into a finite element program. Failure resulting of excessive damage
accumulation in the bioactive glass matrix is predicted by a critical damage
criterion combined with a vanishing element technique. The implication of
particles in the toughening mechanism as well as the damage and crack resistance
improvement in this class of porous biomaterials is highlighted via a parametric
study using the proposed numerical model.
PMID- 29335194
TI - Characterization and mechanical behaviour of reinforced hydroxyapatite coatings
deposited by vacuum plasma spray on SS-316L alloy.
AB - Hydroxyapatite powder reinforced individually with 10wt percentage (wt%) of Al2O3
and ZrO2 (HA + 10wt% Al2O3 and HA + 10wt% ZrO2) was thermally sprayed onto SS
316L substrate with a bond coat of Zirconia by vacuum plasma spray (VPS)
technique. The resulted coatings were heat treated at 700 degrees C for 1h to
study its effects on microstructural and mechanical properties of the deposited
coatings. The characterization of the coatings was carried out using scanning
electron microscope, x-ray diffraction, porosity, surface roughness and
crystallinity using Rietveld analysis. The results indicated that after post
coating heat treatment substantial decrease in porosity was witnessed along with
significant improvement in crystallinity. Besides, the hardness across the cross
section of the coatings and bond strength was considerably improved; however the
hardness of top coat was reduced owing to the loosening of un-melted and
partially melted particles by diffusion process which takes place during heat
treatment.
PMID- 29335195
TI - Periprocedural Anticoagulation for Catheter Ablation of Atrial Fibrillation:
Practical Implications for Perioperative Management.
PMID- 29335196
TI - Percutaneous Transcatheter Valve-in-Valve Implantation for Prosthetic Valve
Disease-An Analysis of Evolving Data and Technology.
PMID- 29335197
TI - Antifungal efficacy of Au@ carbon dots nanoconjugates against opportunistic
fungal pathogen, Candida albicans.
AB - In the current study, we have investigated the toxicological effect of a novel
hydrophilic nanoconjugate gold@carbon dot (Au@CD) and carbon dots (CDs) on the
opportunistic fungal pathogen, Candida albicans. A homogenous experimental
analysis was conducted for determining the toxicity of Au@CDs nanoconjugates of
five different sizes ranging from 22 +/- 2 to 35 +/- 3 nm prepared using the
carbon dots of mean hydrodynamic radius 12 +/- 1 nm. The smallest size of
nanoconjugate was synthesized using 0.3 mg ml-1 HAuCl4 precursor. Our study for
the first time, conclusively establishes the size-dependent toxicity effect of
these characterized nanoconjugates against the abovementioned fungal pathogen.
The MIC80 value of smaller sized Au@CDs nanoconjugates, S1-S3 samples were 250,
500 and 500 MUg ml-1, respectively, while nanoconjugates of Rh diameter greater
than 30 nm (S4 and S5 samples) did not show any toxicity. The results thus
demonstrate that alteration in composition (carbon vs Au@CDs) exhibits a profound
effect on the susceptibility of Candida albicans cells. While a size-dependent
toxicity was observed for the nanoconjugates, CDs were found to be quite toxic
owing to their small size which facilitated their entry into the cells and
challenged the biocompatibility of carbon allotropes.
PMID- 29335198
TI - Triple cell-responsive nanogels for delivery of drug into cancer cells.
AB - In this report, biocompatible nanogels with multi cell-responsiveness (thermo-,
pH- and reduction) were fabricated by in situ cross-linking of alginate (AG)
using cystamine (Cys) as a cross-linker through an emulsion approach, in the
presence of a thermosensitive polymer, poly(N-isopropylacrylamide) (PNIPAM). The
AG/PNIPAM nanogels exhibited an abrupt swelling upon temperature increase from 37
to 25 degrees C under physiological conditions (497 +/- 258 nm at 29 degrees C
and 147 +/- 48 nm at 37 degrees C). The nanogels were easily taken up by cancer
cells at high temperature, where temperature variation could induce toxicity
against cancer cells. Furthermore, the accelerated release under reducible and
acidic microenvironments inside cells, together their thermosensitivity, made the
nanogels selectively deliver drug intracellulary to exert a synergistical
anticancer efficacy, potentiating therir high promise for drug delivery
application.
PMID- 29335199
TI - 3-D mineralized silk fibroin/polycaprolactone composite scaffold modified with
polyglutamate conjugated with BMP-2 peptide for bone tissue engineering.
AB - In the field of bone tissue engineering, an ideal three-dimensional (3-D)
scaffold should not only structurally mimic the extracellular matrix (ECM) in
large tissues but also mechanically support the bone healing process and provide
biochemical cues to induce osteogenesis. In this study, we investigated the
feasibility of functionalisation of scaffolds by coupling polyglutamate acid
conjugated with BMP-2 peptide onto silk fibroin (SF)/polycaprolactone (PCL)
(SF/PCL) blend nanofibers. The morphology, composition, and mineralisation, were
confirmed by FE-SEM, XRD, and FT-IR spectroscopy. The FE-SEM images revealed that
wet-electrospun nanofibrous scaffolds exhibited inter-connected nano/micro-pores
at different levels, and a different morphology was observed on the 3-D SF/PCL
scaffold after mineralisation. Furthermore, the binding property and release
behaviour of the peptide were investigated on this mineralized structure, and
adipose-derived stem cells were seeded on the composite scaffolds to assay their
cytocompatibility and osteogenic differentiation capacities. Results suggest that
the polyglutamate motif (repetitive glutamate amino acids) exhibited markedly
improved binding properties to mineralized nanofibers, and the mineralized 3-D
scaffolds with the conjugated with peptide enhances the mRNA expression of
osteogenic genes. The sponge-like 3-D nanofibrous scaffold mechanically and
biochemically mimics the regenerative process for applications in bone tissue
engineering, including the regeneration of calvarial defects.
PMID- 29335200
TI - Discovery and optimization of phthalazinone derivatives as a new class of potent
dengue virus inhibitors.
AB - Using a dengue replicon cell line-based screening, we identified 3
(dimethylamino)propyl(3-((4-(4-fluorophenyl)-1-oxophthalazin-2(1H)
yl)methyl)phenyl)carbamate (10a) as a potent DENV-2 inhibitor, with an IC50 value
of 0.64 MUM. A series of novel phthalazinone derivatives based on hit 10a were
synthesized and evaluated for their in vitro anti-DENV activity and cytotoxicity.
The subsequent SAR study and optimization led to the discovery of the most
promising compound 14l, which displayed potent anti-DENV-2 activity, with low
IC50 value against DENV-2 RNA replication of 0.13 MUM and high selectivity (SI =
89.2) with acceptable pharmacokinetics profiles.
PMID- 29335201
TI - Antitumor activity of pyrrolizines and their Cu(II) complexes: Design, synthesis
and cytotoxic screening with potential apoptosis-inducing activity.
AB - Two novel series including Schiff bases of the pyrrolizine-5-carboxamides and
their Cu(II) complexes were designed, synthesized and analysed using spectral and
analytical techniques. The analytical results indicated the formation of the
complexes in 1:1 or 1:2 (Metal:Ligand) ratio. The geometry around the Cu centers
was confirmed to be tetrahedral or octahedral. The cytotoxic activity of the new
compounds was evaluated using MCF-7 (human breast adenocarcinoma), A2780 (human
ovary adenocarcinoma) and HT29 (human colon adenocarcinoma), in addition to MRC5
(normal human fetal lung fibroblast) cells using the MTT cytotoxicity assay. The
Schiff base 12c and the Cu complex 13b were the most active in the two series
with IC50 values in the range of 0.14-2.54 MUM against the three cell lines.
Also, the Cu complex 13e showed excellent activity against HT29 with IC50 =
0.05MUM. 7-Cyano-N-(4-methoxyphenyl)-6-((3-phenylallylidene) amino)-2,3-dihydro
1H-pyrrolizine-5-carboxamide (12c) showed high selectivity (6-13 folds) for
cancerous cells over normal cells; and it induced marginal increases in the G1
and S phases of MCF-7 cells during cell cycle analysis, while compound 13b
increased the MCF-7 Sub-G1 proapoptotic population, and blocked cells in the G2-M
phase in a dose dependent manner. The annexin V apoptosis assay revealed the
ability of compounds 12c and 13b to increase the early apoptotic MCF-7 cell
populations two and three fold, respectively. Furthermore, these findings were
supported by data showing that the two compounds (12c and 13b) elicit cytotoxic
activity. Taken together, the data presented in this study warrants further in
vitro and in vivo investigations.
PMID- 29335202
TI - 5-Bromo-oxoisoaporphine platinum(II) complexes exhibit tumor cell cytotoxcicity
via inhibition of telomerase activity and disruption of c-myc G-quadruplex DNA
and mitochondrial functions.
AB - Two platinum(II) complexes [Pt(L)(DMSO)Cl] (1) and [Pt(L)(pn)]Cl (2) with 5-bromo
oxoisoaporphine (H-L) were synthesized. We found that the two new platinum(II)
complexes were more selective for Hep-G2 tumor cells than for normal cells (HL
7702, WI-38 and L-o2 cell lines). 5-Bromine-oxoisoaporphine platinum(II) complex
2 was a telomerase inhibitor targeting c-myc G4, and it triggered Hep-G2 cell
apoptosis more potently than complex 1. Moreover, they induced cell apoptosis via
disruption of mitochondrial functions. Significantly increased ROS level, loss of
Deltapsi, decrease of bcl-2 level, and increase of some of the mitochondria
initiated apoptosis protein levels (including bax, Cyt C, caspase-3, caspase-9,
and apaf-1) were observed in Hep-G2 cells. In brief, complexes 1 and 2 triggered
Hep-G2 cell apoptosis mainly through inhibiting telomerase activity by
interacting with c-myc promoter elements and disruption of mitochondrial pathway.
Our results also showed the effects of second ligands on the in vitro antitumor
activity in the order of pn > Cl and DMSO.
PMID- 29335203
TI - Inhibitor of the human telomerase reverse trancriptase (hTERT) gene promoter
induces cell apoptosis via a mitochondrial-dependent pathway.
AB - Telomerase is aberrantly expressed in many cancers and plays an important role in
the development of cellular immortality and oncogenesis, which makes it a
potential cancer therapeutic target for drug discovery. Here, we constructed a
firefly luciferase reporter driven by the human telomerase reverse trancriptase
(hTERT) gene promoter to screen for inhibitory compounds. Compound 5c was
discovered and shown to significantly inhibit the promoter activity of hTERT
gene. Furthermore, five analogs of compound 5c were synthesized, and compound 8b
was shown to be a more potent inhibitor of hTERT gene promoter activity and
subsequent expression of hTERT mRNA and protein. The viability of HeLa cells was
inhibited by a knockdown of hTERT gene expression, and the same effect was also
observed by treating with compound 8b. Moreover, our results indicated that
compound 8b induced apoptosis of HeLa cells, and activated caspase-9 and caspase
3 enzymes. Taken together, these results suggested that compound 8b down
regulates the expression of hTERT and induces mitochondrial-dependent apoptosis.
PMID- 29335205
TI - Design and synthesis of 2-(4,5,6,7-tetrahydrothienopyridin-2-yl)-benzoimidazole
carboxamides as novel orally efficacious Poly(ADP-ribose)polymerase (PARP)
inhibitors.
AB - The nuclear protein poly(ADP-ribose) polymerases-1/2 (PARP-1/2) are involved in
DNA repair damaged by endogenous or exogenous process. And PARP-1/2 inhibitors
have been proved to be clinically efficacious for DNA repair deficient tumors in
the past decade. We have developed a series of 4,5,6,7-tetrahydrothienopyridin-2
yl benzimidazole carboxamides as novel and potent PARP-1/2 inhibitors. The best
compound resulted from this series is compound 27 which displays excellent PARP-1
and PARP-2 inhibitory activity with IC50 of 18 nM and 42 nM, respectively.
Furthermore, it can selectively kill BRCA2 deficient V-C8 cells with a CC50 of
920 nM. In the MDA-MB-436 (BRCA-1 mutant) xenograft model, this compound was well
tolerated and showed single-agent activity. Based on the results above, compound
27 has been selected as a lead candidate targeting PARP-1/2 and its preclinical
characterization is also underway.
PMID- 29335204
TI - Synthesis and biological evaluation of bifendate derivatives bearing 6,7-dihydro
dibenzo[c,e]azepine scaffold as potential P-glycoprotein and tumor metastasis
inhibitors.
AB - As a continuation of previous research, fifteen bifendate derivatives bearing 6,7
dihydro-dibenzo [c,e]azepine scaffold were synthesized and evaluated as P-gp
medicated multidrug resistance (MDR) reversal agents. Biological evaluation
indicated that compounds 6k and 9c more potently reversed P-gp-mediated MDR than
bifendate and verapamil (VRP) by blocking P-gp mediated drug efflux function and
not by decreasing P-gp expression in K562/A02 MDR cells. Interestingly, wound
healing and chamber migration assay showed that 6k and 9c could significantly
attenuate the migration of MDA-MB-231 cells. Notably, 6k and 9c could markedly
suppress the invasive activity of MDA-MB-231 cells, thus displayed potential anti
metastasis activity. Preliminary mechanism studies indicated that the anti
metastasis activity of 6k and 9c was associated with their inhibitory effect on
the activity and expression of MMP-2 and MMP-9. These results, together with the
MDR reversal results indicated that compounds 6k and 9c might be promising leads
for developing novel anti-cancer agents with P-gp and tumor metastasis inhibitory
activities.
PMID- 29335206
TI - Synthesis and biological evaluation of 4-amino-5-cinnamoylthiazoles as chalcone
like anticancer agents.
AB - A series of 4-amino-5-cinnamoylthiazoles 3a-p were designed and synthesized as
chalcone-like anticancer agents. The synthesized derivatives 3a-p were evaluated
for their in vitro antiproliferative activities against three different human
cancer cell lines including MCF-7, HepG2 and SW480. Most of compounds could
significantly prevent proliferation of tested cell lines. In particular, the
pyrrolidine derivative 3e namely (E)-1-(4-amino-2-(pyrrolidin-1-yl)thiazol-5-yl)
3-(2,4-dichlorophenyl)prop-2-en-1-one showed promising activity, especially
against HepG2 cells (IC50 = 10.6 MUg/ml). Flow cytometric analyses revealed that
the prototype compound 3e can prevent the proliferation of HepG2 cells by
blockade of the cell cycle at the G2 phase and induction of apoptosis.
PMID- 29335207
TI - Synthesis and biological evaluation of 3-(2-aminoethyl) uracil derivatives as
gonadotropin-releasing hormone (GnRH) receptor antagonists.
AB - We investigated a series of uracil analogues by introducing various substituents
on the phenyl ring of the N-3 aminoethyl side chain and evaluated their
antagonistic activity against human gonadotropin-releasing hormone (GnRH)
receptors. Analogues with substituents at the ortho or meta position demonstrated
potent in vitro antagonistic activity. Specifically, the introduction of a 2-OMe
group enhanced nuclear factor of activated T-cells (NFAT) inhibition up to 6-fold
compared to the unsubstituted analogue. We identified compound 12c as a highly
potent GnRH antagonist with moderate CYP inhibition. Compound 12c showed potent
and prolonged LH suppression after a single dose was orally administered in
castrated monkeys compared to a known antagonist, Elagolix. We believe that our
SAR study offers useful insights to design GnRH antagonists as a potential
treatment option for endometriosis.
PMID- 29335208
TI - New findings on the d(TGGGAG) sequence: Surprising anti-HIV-1 activity.
AB - The biological relevance of tetramolecular G-quadruplexes especially as anti-HIV
agents has been extensively reported in the literature over the last years. In
the light of our recent results regarding the slow G-quadruplex folding kinetics
of ODNs based on d(TGGGAG) sequence, here we report a systematic anti-HIV
screening to investigate the impact of the G-quadruplex folding on their anti-HIV
activity. In particular, varying the single stranded concentrations of ODNs, it
has been tested a pool of ODN sample solutions with different G-quadruplex
concentrations. The anti-HIV assays have been designed favouring the limited
kinetics involved in the tetramolecular G4-association based on the d(TGGGAG)
sequence. Aiming to determine the stoichiometry of G-quadruplex structures in the
same experimental conditions of the anti-HIV assays, a native gel electrophoresis
was performed. The gel confirmed the G-quadruplex formation for almost all sample
solutions while showing the formation of high order G4 structures for the more
concentrated ODNs solutions. The most significant result is the discovery of a
potent anti-HIV activity of the G-quadruplex formed by the natural d(TGGGAG)
sequence (IC50 = 14 nM) that, until now, has been reported to be completely
inactive against HIV infection.
PMID- 29335209
TI - Chameleon-like behavior of indolylpiperidines in complex with cholinesterases
targets: Potent butyrylcholinesterase inhibitors.
AB - Alzheimer's disease (AD) is the most common form of dementia worldwide with an
increasing prevalence for the next years. The multifactorial nature of AD
precludes the design of new drugs directed to a single target being probably one
of the reasons for recent failures. Therefore, dual binding site
acetylcholinesterase (AChE) inhibitors have been revealed as cognitive enhancers
and beta-amyloid modulators offering an alternative in AD therapy field. Based on
the dual ligands NP61 and donepezil, the present study reports the synthesis of a
series of indolylpiperidines hybrids to optimize the NP61 structure preserving
the indole nucleus, but replacing the tacrine moiety of NP61 by benzyl piperidine
core found in donepezil. Surprisingly, this new family of indolylpiperidines
derivatives showed very potent and selective hBuChE inhibition. Further studies
of NMR and molecular dynamics have showed the capacity of these hybrid molecules
to change their bioactive conformation depending on the binding site, being
capable to inhibit with different shapes BuChE and residually AChE.
PMID- 29335210
TI - Privileged scaffolds as MAO inhibitors: Retrospect and prospects.
AB - This review aims to be a comprehensive, authoritative, critical, and readable
review of general interest to the medicinal chemistry community because it
focuses on the pharmacological, chemical, structural and computational aspects of
diverse chemical categories as monoamine oxidase inhibitors (MAOIs). Monoamine
oxidases (MAOs), namely MAO-A and MAO-B represent an enormously valuable class of
neuronal enzymes embodying neurobiological origin and functions, serving as
potential therapeutic target in neuronal pharmacotherapy, and hence we have
coined the term "Neurozymes" which is being introduced for the first time ever.
Nowadays, therapeutic attention on MAOIs engrosses two imperative categories; MAO
A inhibitors, in certain mental disorders such as depression and anxiety, and MAO
B inhibitors, in neurodegenerative disorders like Alzheimer's disease (AD) and
Parkinson's disease (PD). The use of MAOIs declined due to some potential side
effects, food and drug interactions, and introduction of other classes of drugs.
However, curiosity in MAOIs is reviving and the recent developments of new
generation of highly selective and reversible MAOIs, have renewed the therapeutic
prospective of these compounds. The initial section of the review emphasizes on
the detailed classification, structural and binding characteristics, therapeutic
potential, current status and future challenges of the privileged pharmacophores.
However, the chemical prospective of privileged scaffolds such as; aliphatic and
aromatic amines, amides, hydrazines, azoles, diazoles, tetrazoles, indoles,
azines, diazines, xanthenes, tricyclics, benzopyrones, and more interestingly
natural products, along with their conclusive SARs have been discussed in the
later segment of review. The last segment of the article encompasses some patents
granted in the field of MAOIs, in a simplistic way.
PMID- 29335211
TI - Synthesis of carbazole derivatives containing chalcone analogs as non
intercalative topoisomerase II catalytic inhibitors and apoptosis inducers.
AB - Novel topoisomerase II (Topo II) inhibitors have gained considerable interest for
the development of anticancer agents. In this study, a series of carbazole
derivatives containing chalcone analogs (CDCAs) were synthesized and investigated
for their Topo II inhibition and cytotoxic activities. The results from Topo II
mediated DNA relaxation assay showed that CDCAs could significantly inhibit the
activity of Topo II, and the structure-activity relationship indicated the
halogen substituent in phenyl ring play an important role in the activity.
Further mechanism studies revealed that CDCAs function as non-intercalative Topo
II catalytic inhibitors. Moreover, some CDCAs showed micromolar cytotoxic
activities. The most potent compound 3h exhibited notable growth inhibition
against four human cancer cell lines. Flow cytometric analysis revealed that
compounds 3d and 3h arrested the HL-60 cells in sub G1 phase by induction of
apoptosis. It was further confirmed by Annexin-V-FITC binding assay. Western blot
analysis revealed that compound 3h induces apoptosis likely through the
activation of caspase proteins.
PMID- 29335212
TI - Synthesis and biological evaluation of novel bavachinin analogs as anticancer
agents.
AB - A library of 28 analogs of bavachinin including aliphatic and aromatic ethers,
epoxide, chalcone, oxime, semicarbazide, oxime ether and triazole derivatives
have been synthesized and evaluated for cytotoxicity against four different human
cancer cell lines. Bio-evaluation studies exhibited better cytotoxic profile for
many analogs compare to bavachinin. Best results were observed for a 1,2,3
triazole analog (17i) with IC50 values 7.72, 16.08, 7.13 and 11.67 MUM against
lung (A549), prostate (PC-3), colon (HCT-116) and breast (MCF-7) cancer cell
lines respectively. This analog showed three and four fold improvement in
cytotoxicity against HCT-116 and A549 cell lines than parent molecule (1).
Structure activity relationship (SAR) study for all synthesized analogs was
carried out. Further, mechanistic study of the lead molecule (17i) revealed that
it inhibits colony formation and in vitro migration of human colon cancer cells
(HCT-116). Also, it induced the morphological changes and mediated the apoptotic
cell death of HCT-116 cells with perturbance in mitochondrial membrane potential
(MMP) and PARP cleavage.
PMID- 29335213
TI - Jietacins, azoxy antibiotics with potent nematocidal activity: Design, synthesis,
and biological evaluation against parasitic nematodes.
AB - Jietacins, an azoxy antibiotic class of chemicals, were isolated from the culture
broth of Streptomyces sp. KP-197. They have a unique structural motif, including
a vinyl azoxy group and a long acyclic aliphatic chain, which is usually branched
but non-branched in the case of jietacin C. During a drug discovery program, we
found that jietacins display potent anthelmintic activity against parasitic
nematodes and that jietacin A has a moderate or low acute toxicity (LD50 > 300
mg/kg) and no mutagenic potential in a mini Ames screen. This suggests that
jietacins have potential for drug discovery research. In order to create a novel
anthelmintic agent, we performed design, synthesis, and biological evaluation of
jietacin derivatives against parasitic nematodes. Of these derivatives, we found
that a fully synthesized simplified derivative exhibited better anthelmintic
activity against three parasitic nematodes than natural jietacins. In addition,
it had a better efficacy in vivo through oral administration against a mouse
nematode. This indicated that the azoxy motif could prove useful as a template
for anthelmintic discovery, possibly creating a class of anthelmintic with novel
skeletons, a potential new mode of action, and providing further insight for
rational drug design.
PMID- 29335215
TI - Removing antimony from waste lead storage batteries alloy by vacuum displacement
reaction technology.
AB - With the wide application of lead acid battery, spent lead acid battery has
become a serious problem to environmental protection and human health. Though
spent battery can be a contaminant if not handled properly, it is also an
important resource to obtain refined lead. Nowadays, the Sb-content in lead
storage batteries is about 0.5-3 wt%, which is higher than the Sb-content in the
crude lead. However, there are few reports about the process of removing antimony
from high-antimony lead bullion. In this study, vacuum displacement reaction
technology, a new process for removing antimony from high-antimony lead melts,
was investigated. During this process, lead oxide was added to the system and
antimony from lead melts was converted into antimony trioxide, which easily was
evaporated under vacuum so that antimony was removed from lead melts. The
experimental results demonstrated that Sb-content in lead melts decreased from
2.5% to 23 ppm under following conditions: mass ratio of PbO/lead bullion of
0.33, residual gas pressure of 30 Pa, melt temperature of 840 degrees C,
reaction time of 60 min. The distillate gotten can be used as by-product to
produce antimony white. Moreover, this study is of importance to recycling of
waste lead storage batteries alloy.
PMID- 29335214
TI - In vivo potent BM635 analogue with improved drug-like properties.
AB - BM635 is the hit compound of a promising anti-TB compound class. Herein we report
systematic variations around the central pyrrole core of BM635 and we describe
the design, synthesis, biological evaluation, pharmacokinetic analysis, as well
as in vivo TB mouse efficacy studies of novel BM635 analogues that show improved
physicochemical properties. This hit-to-lead campaign led to the identification
of a new analogue, 4-((1-isopropyl-5-(4-isopropylphenyl)-2-methyl-1H-pyrrol-3
yl)methyl)morpholine (17), that shows excellent activity (MIC = 0.15 MUM; SI =
133) against drug-sensitive Mycobacterium tuberculosis strains, as well as
efficacy in a murine model of TB infection.
PMID- 29335216
TI - A new screened microbial consortium OEM2 for lignocellulosic biomass
deconstruction and chlorophenols detoxification.
AB - Recalcitrance limits biomass application in biorefinery. It is even more so when
toxic chlorophenols are present. In this study, we screened a microbial
consortium, OEM2, for lignocellulose deconstruction and chlorophenols
detoxification through a short-term and efficient screening process. Microbial
consortium OEM2 had a good buffer capability in the cultivation process and
exhibited a high xylanase activity, with over 85% hemicellulose degradation
within 12 days. Throughout the treatment process, 41.5% rice straw decomposition
on day 12 and around 75% chlorophenols (MCP, 2,4-DCP, 2,4,6-TCP) removal on day
9, were recorded. Moreover, Fourier translation infrared spectroscopy (FTIR)
analysis indicated that chemical bonds and groups (eg. hydrogen-bond, beta-1,4
glycosidic bond, lignin-carbohydrate cross-linking) in the rice straw were
broken. Cuticle and silica layer destruction and subsequent exposed cellulose
fibers were observed by scanning electron microscopy (SEM). Microbial consortium
OEM2 diversity analysis by 16S rRNA gene sequencing indicated that Proteobacteria
(41.3%) was the most abundant phylum and the genera Paenibacillus and Pseudomonas
played an important role in the lignocellulose decomposition and chlorophenols
detoxification. This study developed a faster and more efficient strategy to
screen a specific microbial consortium. And the new microbial consortium, OEM2,
makes lignocellulose more accessible and complex pollutants unproblematic in the
further biorefinery process.
PMID- 29335217
TI - Synthesis and characterisation of calix[4]arene based bis(triazole)
bis(hexahydroquinoline): Probing highly selective fluorescence quenching towards
mercury (Hg2+) analyte.
AB - In the present study, we are reporting the synthesis of a triazoles incorporated
fluorescent hexahydroquinoline appended calix[4]arene 7 and its highly selective
optical recognition ability towards Hg2+. The optical sensor 7 was synthesized
via two different synthetic pathways and unambiguously characterized by mass
spectrometry and NMR spectroscopy. The stoichiometric ratio between 7 and Hg2+
was determined as 1:1 based on Job's plot and ESI-MS analysis. The chemosensor 7
selectively recognized Hg2+ in the presence of competitive cations such as Cu2+,
Cu1+, Co3+, Ni2+, Ag1+, Fe2+, Fe3+, Cr3+, Pb2+, Cd2+, Zn2+, Sn2+, Ti4+, Sb3+,
In3+, Ba2+, Ca2+, and K1+. The limit of detection (LOD) was established as 0.5
MUM on spectrofluorimetric analysis. According to world health organization (WHO)
in guidelines for drinking-water quality, the mercury level in natural occurring
ground and surface water is about ~0.5 MUM (MUg/L). The supra molecule 7 with LOD
(0.5 MUM) could potentially serve effective receptors for Hg2+ cation. The probe
7 was applied effectively for detection of Hg2+ in real water samples (i.e. tap
and deionized water), spiked with Hg2+ (10 MUM) solution. Moreover, the compound
7 showed non-toxicity during cytotoxic assay against human B cells as they retain
their morphology. The supramolecule 7 in living cells showed selectivity towards
Hg2+ in cytotoxic assay with T lymphocytes, evident by morphological changes
observed via AFM analysis.
PMID- 29335218
TI - Environmental benefits and drawbacks of composite fuels based on industrial
wastes and different ranks of coal.
AB - A promising solution to many problems that thermal power industry is facing today
would be switching from conventional coal dust combustion to coal-water slurries
containing petrochemicals (CWSP). Here, we perform an experimental study of the
most hazardous anthropogenic emissions (sulfur and nitrogen oxides) from the
combustion of high-potential CWSP. We identify the main benefits and potential
drawbacks of using CWSP in thermal power industry. A set of components and
additives to CWSP are explored that significantly affect the environmental and
energy performance of fuels. The anthropogenic emissions from the combustion of
CWSP made of widespread coal and oil processing wastes are no higher than those
from coal dust combustion. Using specialized additives to CWSP, we can change the
concentrations of NOx and SOx several times. The most appealing additives to CWSP
are sawdust, straw, charcoal, limestone, and glycerol. They provide better
environmental, economic, and energy performance and improve the rheological
properties of CWSP. Waste oils and oil sludge added to CWSP may impair the
environmental performance but boost the cost and energy efficiency. Using coal
water slurries containing petrochemicals as a fuel at thermal power plants is an
environmentally friendly as well as cost- and energy-efficient way to recover
industrial wastes.
PMID- 29335219
TI - Thermal removal of arsenic from copper concentrates: Three-dimensional isothermal
predominance diagrams for the Cu-As-S-O system.
AB - The three-dimensional predominance volume diagrams (PVDs) for the system Cu-As-S
O were constructed at 900 K using [Formula: see text] as independent coordinates.
The constant total pressure surface was used to identify the equilibrium phases
that are stable at 0.25 atm total pressure. The isobaric surface superimposed on
the predominance diagram provides useful insights into the roasting of complex
copper sulfosalts such as enargite (Cu3AsS4) and tennantite (Cu12As4S13). There
are nine interior invariant points each with four associated condensed phases at
900 K. The expanded diagrams showing the stability volumes of each individual
phase are presented. According to the PVD for the Cu-As-S-O system, the
transformation of enargite to copper sulfate follows the Cu3AsS4->CuS->CuSO4 or
Cu3AsS4->Cu2S->CuS->CuSO4 sequence when the pressure of As4O6g is extremely low.
At high As4O6g pressures however, enargite can directly transform to copper
sulfate.
PMID- 29335220
TI - Adeno-associated virus vector-mediated expression of DJ-1 attenuates learning and
memory deficits in 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47)-treated mice.
AB - Evidence indicates that oxidative stress is the central pathological feature of
2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47)-induced neurotoxicity. Protein
kinase C delta (PKCdelta), an oxidative stress-sensitive kinase, can be
proteolytically cleaved to yield a catalytically active fragment (PKCdelta-CF)
that is involved in various neurodegenerative disorders. Here, we showed that BDE
47 treatment increased ROS, malondialdehyde, and protein carbonyl levels in the
mouse hippocampus. In turn, excessive ROS induced caspase-3-dependent PKCdelta
activation and stimulated NF-kappaB p65 nuclear translocation, resulting in
inflammation in the mouse hippocampus. These changes caused learning and memory
deficits in BDE-47-treated mice. Treatment with Z-DEVD-fmk, a caspase-3
inhibitor, or N-acetyl-L-cysteine, an antioxidant, blocked PKCdelta activation
and subsequently inhibited inflammation, thereby improving learning and memory
deficits in BDE-47-treated mice. Our data further showed that activation of ROS
PKCdelta signaling was associated with DJ-1 downregulation, which exerted
neuroprotective effects against oxidative stress induced by different neurotoxic
agents. Adeno-associated viral vector-mediated DJ-1 overexpression in the
hippocampus effectively inhibited excessive ROS production, suppressed caspase-3
dependent PKCdelta cleavage, blunted inflammation and ultimately reversed
learning and memory deficits in BDE-47-treated mice. Taken together, our results
demonstrate that DJ-1 plays a pivotal role in BDE-47-induced neurotoxic effects
and learning and memory deficits.
PMID- 29335221
TI - Highly efficient solar-driven photocatalytic degradation on environmental
pollutants over a novel C fibers@MoSe2 nanoplates core-shell composite.
AB - As an important member of two-dimensional transition metal dichalcogenides, MoSe2
has a wide range of photoelectrochemical properties. However, MoSe2 alone can not
directly be used as photocatalyst for its poor performance owing to the strong
recombination of photogenerated electron-hole pairs. Here, we propose a novel C
fibers@MoSe2 nanoplates core-shell composite, which was prepared by a facile, one
step thermal evaporation method. The composite has a remarkable feature of
numerous MoSe2 thin nanoplates grown in-situ, densely and even vertically on the
surface of the C fibers. Due to the effective separation of photogenerated
electron-hole pairs promoted by the prompt transfer of photogenerated electrons
through C fibers, compared with commercially available pure MoSe2 powder, such
composite exhibits greatly improved solar-driven photocatalytic activity and high
stability for the degradation of various organic/inorganic environmental
pollutants including methylene blue, rhodamine B, p-chlorophenol and K2Cr2O7
aqueous solutions, showing the great potential for environmental remediation by
degrading toxic industrial chemicals in waste water using sunlight. Moreover,
this one-step thermal evaporation is an easy-handling, eco-friendly and low-cost
synthesis method, which is suitable for large-scale production.
PMID- 29335222
TI - Quasi-polymeric construction of stable perovskite-type LaFeO3/g-C3N4
heterostructured photocatalyst for improved Z-scheme photocatalytic activity via
solid p-n heterojunction interfacial effect.
AB - Materials of perovskite-type structure have attracted considerable attention for
their applications in photocatalysis. In this study, a novel composite of p-type
LaFeO3 microsphere coated with n-type nanosized graphitic carbon nitride
nanosheets was constructed by the quasi-polymeric calcination method with the aid
of electrostatic self-assembly interaction. Results indicate that the LaFeO3/g
C3N4p-n heterostructured photocatalyst obtained, in contrast to the pure
constituents, enabled improved visible-light absorption, and more efficient
separation and migration of charge carriers via solid p-n heterojunction
interfacial effect. Correspondingly, the LaFeO3/g-C3N4 composite allowed for
higher visible-light-responsive photocatalytic activity for the degradation of
Brilliant Blue, which was 16.9 and 7.8 times that of pristine g-C3N4 and LaFeO3,
respectively. The photocatalytic degradation of Brilliant Blue was ascribed to
the combined contributions of the photogenerated holes (h+), superoxide radicals
(O2-) and hydroxyl radicals (OH). Based on solid p-n heterojunction interfacial
interaction, a Z-scheme charge carrier transfer pathway integrated with the dye
sensitization effect is proposed as the underlying mechanism of the
photocatalytic reaction process. Therefore, we believe that the perovskite-type
LaFeO3/g-C3N4 Z-scheme photcatalyst promotes the development of photocatalysis
and holds much promise for environmental remediation.
PMID- 29335223
TI - Electron CHanneling ORientation Determination (eCHORD): An original approach to
crystalline orientation mapping.
AB - We present a proof-of-concept attesting the feasability to obtain orientation
maps of polycrystalline materials within a conventional Scanning Electron
Microscope (SEM) using a standard goniometer and Back Scattered Electron (BSE)
detector. The described method is based on the analysis of the contrast variation
of grains due to the channeling of incident electrons on a rotating sample. On
each pixel of the map, experimental intensity profiles as a function of the
rotation angle are obtained and compared with simulated ones to retrieve the
orientation. From first results on aluminum polycrystals, the angular resolution
is estimated to be better than one degree.
PMID- 29335224
TI - Adaptive-scanning, near-minimum-deformation atomic force microscope imaging of
soft sample in liquid: Live mammalian cell example.
AB - In this paper, an adaptive-scanning mode (ASM) of atomic force microscope (AFM)
with near-minimum sample deformation is proposed for imaging live biological
samples in liquid. Conventional contact mode (CM) imaging of live cells is rather
slow (scan rate < 0.2 Hz), and as the imaging speed increases, significant
deformation of the soft and highly corrugated cell membrane is induced. Such a
low speed CM imaging of live biological samples is not only time consuming, but
also incapable of capturing dynamic biological evolutions occurring in seconds to
minutes. The proposed ASM approach aims to address these issues through two
synergetic efforts integrated together. First, an adaptive-scanning technique is
proposed to optimally adjust the lateral scanning speed to accommodate the sample
topography variation and the probe-sample interaction force, so that the scanning
caused sample deformation is maintained below the threshold value while the
overall imaging time is minimized. Secondly, a data-driven iterative feedforward
control is integrated to the vertical feedback loop along with a gradient-based
optimization of the deflection set-point to substantially improve the tracking of
the sample topography while maintaining the vertical sample deformation around
the minimal. The ASM technique is experimentally validated through imaging live
human prostate cancer cells on AFM. The experimental results demonstrate that
compared to the conventional CM imaging, the imaging speed is increased over
eight times without loss of tracking the topography details of the live cell
membrane, and the probe-sample interaction force is substantially reduced.
PMID- 29335225
TI - A systematic comparison of on-axis and off-axis transmission Kikuchi diffraction.
AB - The capabilities of the novel on-axis transmission Kikuchi diffraction (TKD)
technique were explored in a systematic comparison with conventional off-axis
TKD. The effect of experimental parameters on the appearance of on-axis and off
axis Kikuchi patterns was measured and discussed. In contrast to off-axis TKD, on
axis TKD is more sensitive to changes in beam current and beam energy and less
sensitive to changes in working distance and detector distance. Moreover, on-axis
TKD has a distinct advantage over off-axis TKD due to enhanced pattern intensity,
which allows reduction of the beam current or an increase in the acquisition
rate. The physical and effective spatial resolution were measured with detector
typical parameters. Even though the spatial resolution of both configurations did
not differ significantly under test conditions, on-axis TKD enables measurement
over large areas with the determined resolution, whereas off-axis TKD is more
sensitive to beam drift. Band detection by the Hough-transform led to indexing
of, on average, one additional Kikuchi band when measuring with on-axis TKD
compared to off-axis TKD and operated more stable on on-axis patterns.
PMID- 29335226
TI - Genomic and metabolic characterization of spoilage-associated Pseudomonas
species.
AB - Pseudomonas are common spoilage agents of aerobically stored fresh foods. Their
ability to cause spoilage is species- and may be strain-specific. To improve our
understanding of the meat and milk spoilage agents Pseudomonas fragi and
Pseudomonas lundensis, we sequenced the genomes of 12 P. fragi and seven P.
lundensis isolates. These genomes provided a dataset for genomic analyses. Key
volatile organic compounds (VOCs) produced or metabolised by the isolates were
determined during their growth on a beef paste and where possible, metabolic
activity was associated with gene repertoire. Genome analyses showed that the
isolates included in this work may belong to more than two Pseudomonas species
with possible spoilage potential. Pan-genome analyses demonstrated a high degree
of diversity among the P. fragi and genetic flexibility and diversity may be
traits of both species. Growth of the P. lundensis isolates was characterised by
the production of large amounts of 1-undecene, 5-methyl-2-hexanone and methyl-2
butenoic acid. P. fragi isolates produced extensive amounts of methyl and ethyl
acetate and the production of methyl esters predominated over ethyl esters. Some
of the P. fragi produced extremely low levels of VOCs, highlighting the
importance of strain-specific studies in food matrices. Furthermore, although
usually not considered to be denitrifiers, all isolates generated molecular
nitrogen, indicating that at least some steps of this pathway are intact.
PMID- 29335227
TI - Potential of yeasts isolated from dry-cured ham to control ochratoxin A
production in meat models.
AB - The environmental conditions reached during the ripening of dry-cured meat
products favour the proliferation of moulds on their surface. Some of these
moulds are hazardous to consumers because of their ability to produce ochratoxin
A (OTA). Biocontrol using Debaryomyces hansenii could be a suitable strategy to
prevent the growth of ochratoxigenic moulds and OTA accumulation in dry-cured
meat products. The aim of this work was to evaluate the ability of two strains of
D. hansenii to control the growth and OTA production of Penicillium verrucosum in
a meat model under water activities (aw) values commonly reached during the dry
cured meat product ripening. The presence of D. hansenii strains triggered a
lengthening of the lag phase and a decrease of the growth rate of P. verrucosum
in meat-based media at 0.97 and 0.92 aw. Both D. hansenii strains significantly
reduced OTA production (between 85.16 and 92.63%) by P. verrucosum in the meat
based medium at 0.92 aw. Neither absorption nor detoxification of OTA by D.
hansenii strains seems to be involved. However, a repression of the expression of
the non-ribosomal peptide synthetase (otanpsPN) gene linked to the OTA
biosynthetic pathway was observed in the presence of D. hansenii. To confirm the
protective role of D. hansenii strains, they were inoculated together with P.
verrucosum Pv45 in dry-fermented sausage and dry-cured ham slices. Although P.
verrucosum Pv45 counts were not affected by the presence of D. hansenii in both
meat matrices, a reduction of OTA amount was observed. Therefore, the effect of
D. hansenii strains on OTA accumulation should be attributed to a reduction at
transcriptional level. Consequently, native D. hansenii can be useful as
biocontrol agent in dry-cured meat products for preventing the hazard associated
with the presence of OTA.
PMID- 29335228
TI - Irreversible electroporation for locally advanced pancreatic cancer through a
minimally invasive surgery supported by laparoscopic ultrasound.
AB - INTRODUCTION: Pancreatic cancer is one of the most lethal cancers worldwide, with
5-years survival rate as low as 6%. The majority of pancreatic cancer patients
present locally advanced or metastatic disease at diagnosis. Typically, patients
affected by locally advanced pancreatic cancer (LAPC) do not undergo radical
surgery but are treated with focal ablative therapies. However, a high rate of
morbidity due to the heat sink effect has limited the application of ablative
techniques on a routine basis in LAPC patients. Irreversible electroporation
(IRE) has proved to be a new method of LAPC ablation. PRESENTATION OF THE CASE: A
69-year-old woman affected by LAPC with good response to systemic chemotherapy
with FOLFIRINOX and residual 35 mm mass in the neck of the pancreas underwent to
IRE through a minimally invasive surgical approach under laparoscopic ultrasound
guide. The post-operative course was uneventful and the patient was discharged
after 5 days. Six months after surgery she had no evidence of distant or
recurrent disease. DISCUSSION: IRE has previously shown promising results in the
treatment of LAPC, with relatively acceptable morbidity rates and improvement of
survival. We report on the application of IRE through a minimally invasive
surgical approach supported by laparoscopic ultrasound. CONCLUSION: In
conclusion, we propose a novel technical approach that combines the benefits of
IRE on the treatment of patients affected by LAPC with the advantages of
laparoscopic surgery.
PMID- 29335229
TI - Ciliated cyst of the gallbladder: A new case and literature review.
AB - INTRODUCTION: The ciliated cyst is a rare anomaly that develops from the anterior
primitive intestine. Its localization is essentially supra diaphragmatic. It's
localization in the gallbladder is very uncommon. CASE REPORT: We report the
first case in Tunisia of a ciliated cyst of the gallbladder in a 34 years old
woman who was operated for a gallbladder stone and in whom the discovery of a
cystic mass attached to the neck of the gallbladder was preoperatively. The
pathologic study did conclude to a ciliated cyst. DISCUSSION: The ciliated cyst
of the gallbladder is a benign congenital lesion that develops from the anterior
primitive intestine. The most frequent clinical symptom is abdominal pain and the
median age is 45 years old. The most frequent location is the neck. This
pathology affects women more than men. Abdominal ultrasound is not very specific
exam and describes the ciliated cyst as a cystic lesion often anechogenic and
sometimes hyperechogenic. The CT-scan as well as the abdominal MRI are very
helpful of the diagnosis. The positif diagnosis of ciliated cyst is histological.
CONCLUSION: The recommended current treatment for this rare pathology is surgery
and it consists of a celioscopic cholecystectomie. The place of conservatory
treatment hasn't been established due to the rarity of described case and the
possibility of degeneration.
PMID- 29335230
TI - Application of a health risk assessment model for cattle exposed to pesticides in
contaminated drinking waters: A study case from the Pampas region, Argentina.
AB - Using the USEPA methodology we estimated the probabilistic chronic risks for
calves and adult cows due to pesticide exposure through oral intake of
contaminated surface and ground waters in Tres Arroyos County (Argentina).
Because published data on pesticide toxicity endpoints for cows are scarce, we
used threshold levels based on interspecies extrapolation methods. The studied
waters showed acceptable quality for cattle production since none of the
pesticides were present at high-enough concentrations to potentially affect cow
health. Moreover, ground waters had better quality than surface waters, with
dieldrin and deltamethrin being the pesticides associated with the highest risk
values in the former and the latter water compartments, respectively. Our study
presents a novel use of the USEPA risk methodology proving it is useful for water
quality evaluation in terms of pesticide toxicity for cattle production. This
approach represents an alternative tool for water quality management in the
absence of specific cattle pesticide regulatory limits.
PMID- 29335231
TI - Reinvestigating the role of reactive species in the oxidation of organic co
contaminants during Cr(VI) reactions with sulfite.
AB - Experimental work was undertaken in this study to re-investigate the mechanisms
and active species responsible for oxidation of co-contaminants in the
Cr(VI)/HSO3- reaction system. Batch experiments showed that the degradation rates
of 4-chlorophenol (4-CP) correlated well with the rates of Cr(VI) reduction by
sulfite in the same solutions, and that O2(aq) was necessary for the oxidation of
4-CP. Multiple lines of evidences indicate that Cr(VI)/HSO3- reaction is a SO4-
based oxidation process. SO3- was generated in Cr(VI)/HSO3- system based on the
electron spin resonance spectra, which could be transformed to secondary radicals
(SO4-, SO5-, and HO). The contribution of SO5- was ruled out through almost
complete inhibition of methanol (MeOH) on 4-CP degradation. Considering the
negligible inhibition of tert-butanol (TBA) on 4-CP degradation, SO4- was
identified to be reactive species in Cr(VI)/HSO3- process. This result was
further verified by almost no degradation of nitrobenzene and the inhibiting
effect of Cl- in Cr(VI)/HSO3- process. This mechanism is beneficial to
application of Cr(VI)/HSO3- system in wastewater treatment.
PMID- 29335232
TI - Smartphone App Using Mindfulness Meditation for Women With Chronic Pelvic Pain
(MEMPHIS): Protocol for a Randomized Feasibility Trial.
AB - BACKGROUND: Female chronic pelvic pain (CPP) is defined as intermittent or
constant pelvic or lower abdominal pain occurring in a woman for at least 6
months. Up to a quarter of women are estimated to be affected by CPP worldwide
and it is responsible for one fifth of specialist gynecological referrals in the
United Kingdom. Psychological interventions are commonly utilized. As waiting
times and funding capacity impede access to face-to-face consultations, supported
self-management (SSM) has emerged as a viable alternative. Mindfulness meditation
is a potentially valuable SSM tool, and in the era of mobile technology, this can
be delivered to the individual user via a smartphone app. OBJECTIVE: To assess
the feasibility of conducting a trial of a mindfulness meditation intervention
delivered by a mobile phone app for patients with CPP. The main feasibility
objectives were to assess patient recruitment and app adherence, to obtain
information to be used in the sample size estimate of a future trial, and to
receive feedback on usability of the app. METHODS: Mindfulness Meditation for
Women With Chronic Pelvic Pain (MEMPHIS) is a three-arm feasibility trial, that
took place in two hospitals in the United Kingdom. Eligible participants were
randomized in a 1:1:1 ratio to one of three treatment arms: (1) the intervention
arm, consisting of a guided, spoken mindfulness meditation app; (2) an active
control arm, consisting of a progressive muscle relaxation app; and (3) usual
care (no app). Participants were followed-up for 6 months. Key feasibility
outcomes included the time taken to recruit all patients for the study,
adherence, and estimates to be used in the sample size calculation for a
subsequent full-scale trial. Upon completion of the feasibility trial we will
conduct focus groups to explore app usability and reasons for noncompliance.
RESULTS: Recruitment for MEMPHIS took place between May 2016 and September 2016.
The study was closed March 2017 and the report was submitted to the NIHR on
October 26, 2017. CONCLUSIONS: This feasibility trial will inform the design of a
large multicentered trial to assess the clinical effectiveness of mindfulness
meditation delivered via a smartphone app for the treatment of CPP. TRIAL
REGISTRATION: ClinicalTrials.gov: NCT02721108;
https://clinicaltrials.gov/ct2/show/NCT02721108 (Archived by WebCite at
http://www.webcitation.org/6wLMAkuaU); BioMed Central: ISRCTN10925965;
https://www.isrctn.com/ISRCTN10925965 (Archived by WebCite at
http://www.webcitation.org/6wLMVLuys).
PMID- 29335233
TI - Internet-Based Group Intervention for Ovarian Cancer Survivors: Feasibility and
Preliminary Results.
AB - BACKGROUND: Development of psychosocial group interventions for ovarian cancer
survivors has been limited. Drawing from elements of cognitive-behavioral stress
management (CBSM), mindfulness-based stress reduction (MBSR), and acceptance and
commitment therapy (ACT), we developed and conducted preliminary testing of an
Internet-based group intervention tailored specifically to meet the needs of
ovarian cancer survivors. The Internet-based platform facilitated home delivery
of the psychosocial intervention to a group of cancer survivors for whom
attending face-to-face programs could be difficult given their physical
limitations and the small number of ovarian cancer survivors at any one treatment
site. OBJECTIVE: The aim of this study was to develop, optimize, and assess the
usability, acceptability, feasibility, and preliminary intended effects of an
Internet-based group stress management intervention for ovarian cancer survivors
delivered via a tablet or laptop. METHODS: In total, 9 ovarian cancer survivors
provided feedback during usability testing. Subsequently, 19 survivors
participated in 5 waves of field testing of the 10-week group intervention led by
2 psychologists. The group met weekly for 2 hours via an Internet-based
videoconference platform. Structured interviews and weekly evaluations were used
to elicit feedback on the website and intervention content. Before and after the
intervention, measures of mood, quality of life (QOL), perceived stress, sleep,
and social support were administered. Paired t tests were used to examine changes
in psychosocial measures over time. RESULTS: Usability results indicated that
participants (n=9) performed basic tablet functions quickly with no errors and
performed website functions easily with a low frequency of errors. In the field
trial (n=19), across 5 groups, the 10-week intervention was well attended.
Perceived stress (P=.03) and ovarian cancer-specific QOL (P=.01) both improved
significantly during the course of the intervention. Trends toward decreased
distress (P=.18) and greater physical (P=.05) and functional well-being (P=.06)
were also observed. Qualitative interviews revealed that the most common
obstacles participants experienced were technical issues and the time commitment
for practicing the techniques taught in the program. Participants reported that
the intervention helped them to overcome a sense of isolation and that they
appreciated the ability to participate at home. CONCLUSIONS: An Internet-based
group intervention tailored specifically for ovarian cancer survivors is highly
usable and acceptable with moderate levels of feasibility. Preliminary
psychosocial outcomes indicate decreases in perceived stress and improvements in
ovarian cancer-specific QOL following the intervention. A randomized clinical
trial is needed to demonstrate the efficacy of this promising intervention for
ovarian cancer survivors.
PMID- 29335234
TI - A Patient-Held Smartcard With a Unique Identifier and an mHealth Platform to
Improve the Availability of Prenatal Test Results in Rural Nigeria: Demonstration
Study.
AB - BACKGROUND: Community-based strategies to test for HIV, hepatitis B virus (HBV),
and sickle cell disease (SCD) have expanded opportunities to increase the
proportion of pregnant women who are aware of their diagnosis. In order to use
this information to implement evidence-based interventions, these results have to
be available to skilled health providers at the point of delivery. Most
electronic health platforms are dependent on the availability of reliable
Internet connectivity and, thus, have limited use in many rural and resource
limited settings. OBJECTIVE: Here we describe our work on the development and
deployment of an integrated mHealth platform that is able to capture medical
information, including test results, and encrypt it into a patient-held smartcard
that can be read at the point of delivery without the need for an Internet
connection. METHODS: We engaged a team of implementation scientists, public
health experts, and information technology specialists in a requirement-gathering
process to inform the design of a prototype for a platform that uses smartcard
technology, database deployment, and mobile phone app development. Key design
decisions focused on usability, scalability, and security. RESULTS: We
successfully designed an integrated mHealth platform and deployed it in 4 health
facilities across Benue State, Nigeria. We developed the Vitira Health platform
to store test results of HIV, HBV, and SCD in a database, and securely encrypt
the results on a Quick Response code embedded on a smartcard. We used a mobile
app to read the contents on the smartcard without the need for Internet
connectivity. CONCLUSIONS: Our findings indicate that it is possible to develop a
patient-held smartcard and an mHealth platform that contains vital health
information that can be read at the point of delivery using a mobile phone-based
app without an Internet connection. TRIAL REGISTRATION: ClinicalTrials.gov
NCT03027258; https://clinicaltrials.gov/ct2/show/NCT03027258 (Archived by WebCite
at http://www.webcitation.org/6owR2D0kE).
PMID- 29335235
TI - VA FitHeart, a Mobile App for Cardiac Rehabilitation: Usability Study.
AB - BACKGROUND: Cardiac rehabilitation (CR) improves outcomes for patients with
ischemic heart disease or heart failure but is underused. New strategies to
improve access to and engagement in CR are needed. There is considerable interest
in technology-facilitated home CR. However, little is known about patient
acceptance and use of mobile technology for CR. OBJECTIVE: The aim of this study
was to develop a mobile app for technology-facilitated home CR and seek to
determine its usability. METHODS: We recruited patients eligible for CR who had
access to a mobile phone, tablet, or computer with Internet access. The mobile
app includes physical activity goal setting, logs for tracking physical activity
and health metrics (eg, weight, blood pressure, and mood), health education,
reminders, and feedback. Study staff demonstrated the mobile app to participants
in person and then observed participants completing prespecified tasks with the
mobile app. Participants completed the System Usability Scale (SUS, 0-100), rated
likelihood to use the mobile app (0-100), questionnaires on mobile app use, and
participated in a semistructured interview. The Unified Theory of Acceptance and
Use of Technology and the Theory of Planned Behavior informed the analysis. On
the basis of participant feedback, we made iterative revisions to the mobile app
between users. RESULTS: We conducted usability testing in 13 participants. The
first version of the mobile app was used by the first 5 participants, and revised
versions were used by the final 8 participants. From the first version to revised
versions, task completion success rate improved from 44% (11/25 tasks) to 78%
(31/40 tasks; P=.05), SUS improved from 54 to 76 (P=.04; scale 0-100, with 100
being the best usability), and self-reported likelihood of use remained high at
76 and 87 (P=.30; scale 0-100, with 100 being the highest likelihood). In
interviews, patients expressed interest in tracking health measures ("I think
it'll be good to track my exercise and to see what I'm doing"), a desire for
introductory training ("Initially, training with a technical person, instead of
me relying on myself"), and an expectation for sharing data with providers ("It
would also be helpful to share with my doctor, it just being a matter of clicking
a button and sharing it with my doctor"). CONCLUSIONS: With participant feedback
and iterative revisions, we significantly improved the usability of a mobile app
for CR. Patient expectations for using a mobile app for CR include tracking
health metrics, introductory training, and sharing data with providers. Iterative
mixed-method evaluation may be useful for improving the usability of health
technology.
PMID- 29335236
TI - Tanzania Health Information Technology (T-HIT) System: Pilot Test of a Tablet
Based System to Improve Prevention of Mother-to-Child Transmission of HIV.
AB - BACKGROUND: The prevention of mother-to-child transmission (PMTCT) of HIV
requires innovative solutions. Although routine monitoring is effective in some
areas, standardized and easy-to-scale solutions to identify and monitor pregnant
women, test them for HIV, and treat them and their children is still lacking.
Mobile health (mHealth) offers opportunities for surveillance and reporting in
rural areas of low- and middle-income countries. OBJECTIVE: The aim of this study
was to document the preliminary impacts of the Tanzania Health Information
Technology (T-HIT) system mHealth intervention aimed at health workers for PMTCT
care delivery and capacity building in a rural area of Tanzania. METHODS: We
developed T-HIT as a tablet-based system for an electronic data collection system
designed to capture and report PMTCT data during antenatal, delivery, and
postnatal visits in Misungwi, Tanzania. T-HIT was tested by health workers in a
pilot randomized trial comparing seven sites using T-HIT assigned at random to
seven control sites; all sites maintained standard paper record-keeping during
the pilot intervention period. We compared numbers of antenatal visits, number of
HIV tests administered, and women testing positive across all sites. RESULTS:
Health workers recorded data from antenatal visits for 1530 women; of these, 695
(45.42%) were tested for HIV and 3.59% (55/1530) tested positive. Health workers
were unable to conduct an HIV test for 103 women (6.73%, 103/1530) because of
lack of reagent, which is not captured on paper logs. There was no difference in
the activity level for testing when comparing sites T-HIT to non-T-HIT sites. We
observed a significant postintervention increase in the numbers of women testing
positive for HIV compared with the preintervention period (P=.04), but this was
likely not attributable to the T-HIT system. CONCLUSIONS: T-HIT had a high degree
of acceptability and feasibility and is perceived as useful by health workers,
who documented more antenatal visits during the pilot intervention compared with
a traditional system of paper logs, suggesting potential for improvements in
antenatal care for women at risk for HIV.
PMID- 29335237
TI - "Why Do They Need to Check Me?" Patient Participation Through eHealth and the
Doctor-Patient Relationship: Qualitative Study.
AB - BACKGROUND: Roles in the doctor-patient relationship are changing and patient
participation in health care is increasingly emphasized. Electronic health
(eHealth) services such as patient accessible electronic health records (PAEHRs)
have been implemented to support patient participation. Little is known about
practical use of PAEHR and its effect on roles of doctors and patients.
OBJECTIVE: This qualitative study aimed to investigate how physicians view the
idea of patient participation, in particular in relation to the PAEHR system.
Hereby, the paper aims to contribute to a deeper understanding of physicians'
constructions of PAEHR, roles in the doctor-patient relationship, and levels and
limits of involvement. METHODS: A total of 12 semistructured interviews were
conducted with physicians in different fields. Interviews were transcribed,
translated, and a theoretically informed thematic analysis was performed.
RESULTS: Two important aspects were identified that are related to the doctor
patient relationship: roles and involvement. The physicians viewed their role as
being the ones to take on the responsibility, determining treatment options, and
to be someone who should be trusted. In relation to the patient's role, lack of
skills (technical or regarding medical jargon), motives to read, and patients'
characteristics were aspects identified in the interviews. Patients were often
referred to as static entities disregarding their potential to develop skills and
knowledge over time. Involvement captures aspects that support or hinder patients
to take an active role in their care. CONCLUSIONS: Literature of at least two
decades suggests an overall agreement that the paternalistic approach in health
care is inappropriate, and a collaborative process with patients should be
adopted. Although the physicians in this study stated that they, in principle,
were in favor of patient participation, the analysis found little support in
their descriptions of their daily practice that participation is actualized. As
seen from the results, paternalistic practices are still present, even if
professionals might not be aware of this. This can create a conflict between
patients who strive to become more informed and their questions being interpreted
as signs of critique and mistrust toward the physician. We thus believe that the
full potential of PAEHRs is not reached yet and argue that the concept of patient
empowerment is problematic as it triggers an interpretation of "power" in health
care as a zero-sum, which is not helpful for the maintenance of the relationship
between the actors. Patient involvement is often discussed merely in relation to
decision making; however, this study emphasizes the need to include also
sensemaking and learning activities. This would provide an alternative
understanding of patients asking questions, not in terms of "monitoring the
doctor" but to make sense of the situation.
PMID- 29335240
TI - "Arrogant" surgeon fined for writing his initials on patients' livers.
PMID- 29335238
TI - Automating Quality Measures for Heart Failure Using Natural Language Processing:
A Descriptive Study in the Department of Veterans Affairs.
AB - BACKGROUND: We developed an accurate, stakeholder-informed, automated, natural
language processing (NLP) system to measure the quality of heart failure (HF)
inpatient care, and explored the potential for adoption of this system within an
integrated health care system. OBJECTIVE: To accurately automate a United States
Department of Veterans Affairs (VA) quality measure for inpatients with HF.
METHODS: We automated the HF quality measure Congestive Heart Failure Inpatient
Measure 19 (CHI19) that identifies whether a given patient has left ventricular
ejection fraction (LVEF) <40%, and if so, whether an angiotensin-converting
enzyme inhibitor or angiotensin-receptor blocker was prescribed at discharge if
there were no contraindications. We used documents from 1083 unique inpatients
from eight VA medical centers to develop a reference standard (RS) to train
(n=314) and test (n=769) the Congestive Heart Failure Information Extraction
Framework (CHIEF). We also conducted semi-structured interviews (n=15) for
stakeholder feedback on implementation of the CHIEF. RESULTS: The CHIEF
classified each hospitalization in the test set with a sensitivity (SN) of 98.9%
and positive predictive value of 98.7%, compared with an RS and SN of 98.5% for
available External Peer Review Program assessments. Of the 1083 patients
available for the NLP system, the CHIEF evaluated and classified 100% of cases.
Stakeholders identified potential implementation facilitators and clinical uses
of the CHIEF. CONCLUSIONS: The CHIEF provided complete data for all patients in
the cohort and could potentially improve the efficiency, timeliness, and utility
of HF quality measurements.
PMID- 29335239
TI - Comparing Diet and Exercise Monitoring Using Smartphone App and Paper Diary: A
Two-Phase Intervention Study.
AB - BACKGROUND: There is increasing recognition that personalized approaches may be
more effective in helping people establish healthier eating patterns and exercise
more, and that this approach may be particularly effective in adolescents.
OBJECTIVE: The objective of this study was to investigate the use of a smartphone
app (FoodWiz2) in supporting healthy lifestyle choices in adolescence. METHODS:
Participants (N=34: 11 male, 23 female) aged 16-19 years in full- or part-time
education were recruited from sixth form colleges, schools, and other further
education establishments in Norfolk and Suffolk, United Kingdom, between February
and May 2015. Participants recorded food intake and exercise using a paper diary
for 4-5 weeks and then used the app for the same duration. Initial nutrition
education and general support were provided during the paper diary use, but the
app included personalized messages sent in response to app activity. At the end
of each study phase, participants completed an online questionnaire to describe
their experience of using the paper diary and app. RESULTS: Record completion
declined throughout the study, possibly affected by examination pressure. Food
intake data showed increased fruit consumption and significantly reduced
consumption of chocolate snacks (P=.01) and fizzy drinks (P=.002) among
participants using the app. Questionnaire responses indicated that the app was
generally preferred to the paper diary, in particular, the app was seen as less
boring to use (P=.03) and more acceptable in social settings (P<.001).
CONCLUSIONS: This app-based approach has shown the potential for a more effective
approach to improving adolescent diet and exercise levels.
PMID- 29335241
TI - The MFHR1 Fusion Protein Is a Novel Synthetic Multitarget Complement Inhibitor
with Therapeutic Potential.
AB - The complement system is essential for host defense, but uncontrolled complement
system activation leads to severe, mostly renal pathologies, such as atypical
hemolytic uremic syndrome or C3 glomerulopathy. Here, we investigated a novel
combinational approach to modulate complement activation by targeting C3 and the
terminal pathway simultaneously. The synthetic fusion protein MFHR1 links the
regulatory domains of complement factor H (FH) with the C5 convertase/C5b-9
inhibitory fragment of the FH-related protein 1. In vitro, MFHR1 showed cofactor
and decay acceleration activity and inhibited C5 convertase activation and C5b-9
assembly, which prevented C3b deposition and reduced C3a/C5a and C5b-9
generation. Furthermore, this fusion protein showed the ability to escape
deregulation by FH-related proteins and form multimeric complexes with increased
inhibitory activity. In addition to substantially inhibiting alternative and
classic pathway activation, MFHR1 blocked hemolysis mediated by serum from a
patient with aHUS expressing truncated FH. In FH-/- mice, MFHR1 administration
augmented serum C3 levels, reduced abnormal glomerular C3 deposition, and
ameliorated C3 glomerulopathy. Taking the unique design of MFHR1 into account, we
suggest that the combination of proximal and terminal cascade inhibition together
with the ability to form multimeric complexes explain the strong inhibitory
capacity of MFHR1, which offers a novel basis for complement therapeutics.
PMID- 29335242
TI - Effect of Bariatric Surgery on CKD Risk.
AB - Obesity is linked to the development and progression of CKD, but whether
bariatric surgery protects against CKD is poorly understood. We, therefore,
examined whether bariatric surgery influences CKD risk. The study included 2144
adults who underwent bariatric surgery from March of 2006 to April of 2009 and
participated in the Longitudinal Assessment of Bariatric Surgery-2 Study cohort.
The primary outcome was CKD risk categories as assessed by the Kidney Disease
Improving Global Outcomes (KDIGO) consortium criteria using a combination of eGFR
and albuminuria. Patients were 79% women and 87% white, with a median age of 46
years old. Improvements were observed in CKD risk at 1 and 7 years after surgery
in patients with moderate baseline CKD risk (63% and 53%, respectively), high
baseline risk (78% and 56%, respectively), and very high baseline risk (59% and
23%, respectively). The proportion of patients whose CKD risk worsened was <=10%;
five patients developed ESRD. Sensitivity analyses using year 1 as baseline to
minimize the effect of weight loss on serum creatinine and differing eGFR
equations offered qualitatively similar results. Treatment with bariatric surgery
associated with an improvement in CKD risk categories in a large proportion of
patients for up to 7 years, especially in those with moderate and high baseline
risk. These findings support consideration of CKD risk in evaluation for
bariatric surgery and further study of bariatric surgery as a treatment for high
risk obese patients with CKD.
PMID- 29335244
TI - Making the Right Decision: Do Clinical Decision Support Systems for AKI Improve
Patient Outcomes?
PMID- 29335243
TI - Nephronectin Regulates Mesangial Cell Adhesion and Behavior in Glomeruli.
AB - A critical aspect of kidney function occurs at the glomerulus, the capillary
network that filters the blood. The glomerular basement membrane (GBM) is a key
component of filtration, yet our understanding of GBM interactions with mesangial
cells, specialized pericytes that provide structural stability to glomeruli, is
limited. We investigated the role of nephronectin (Npnt), a GBM component and
known ligand of alpha8beta1 integrin. Immunolocalization and in situ
hybridization studies in kidneys of adult mice revealed that nephronectin is
produced by podocytes and deposited into the GBM. Conditional deletion of Npnt
from nephron progenitors caused a pronounced increase in mesangial cell number
and mesangial sclerosis. Nephronectin colocalized with alpha8beta1 integrin to
novel, specialized adhesion structures that occurred at sites of mesangial cell
protrusion at the base of the capillary loops. Absence of nephronectin disrupted
these adhesion structures, leading to mislocalization of alpha8beta1. Podocyte
specific deletion of Npnt also led to mesangial sclerosis in mice. These results
demonstrate a novel role for nephronectin and alpha8beta1 integrin in a newly
described adhesion complex and begin to uncover the molecular interactions
between the GBM and mesangial cells, which govern mesangial cell behavior and may
have a role in pathologic states.
PMID- 29335245
TI - CDK9-mediated phosphorylation controls the interaction of TIP60 with the
transcriptional machinery.
AB - The acetyltransferase TIP60 is regulated by phosphorylation, and we have
previously shown that phosphorylation of TIP60 on S86 by GSK-3 promotes p53
mediated induction of the BCL-2 protein PUMA. TIP60 phosphorylation by GSK-3
requires a priming phosphorylation on S90, and here, we identify CDK9 as a
TIP60S90 kinase. We demonstrate that a phosphorylation-deficient mutant,
TIP60S90A, exhibits reduced interaction with chromatin, histone 3 and RNA Pol II,
while its association with the TIP60 complex subunit EPC1 is not affected.
Consistently, we find a diminished association of TIP60S90A with the MYC gene. We
show that cells expressing TIP60S90A, but also TIP60S86A, which retains S90
phosphorylation, exhibit reduced histone 4 acetylation and proliferation. Thus,
our data indicate that, during transcription, phosphorylation of TIP60 at two
sites has different regulatory effects on TIP60, whereby S90 phosphorylation
controls association with the transcription machinery, and S86 phosphorylation is
regulating TIP60 HAT activity.
PMID- 29335247
TI - The genetics of domestication: Research into the domestication of livestock and
companion animals sheds light both on their "evolution" and human history.
PMID- 29335246
TI - Differential roles of ERRFI1 in EGFR and AKT pathway regulation affect cancer
proliferation.
AB - AKT signaling is modulated by a complex network of regulatory proteins and is
commonly deregulated in cancer. Here, we present a dual mechanism of AKT
regulation by the ERBB receptor feedback inhibitor 1 (ERRFI1). We show that in
cells expressing high levels of EGFR, ERRF1 inhibits growth and enhances
responses to chemotherapy. This is mediated in part through the negative
regulation of AKT signaling by direct ERRFI1-dependent inhibition of EGFR In
cells expressing low levels of EGFR, ERRFI1 positively modulates AKT signaling by
interfering with the interaction of the inactivating phosphatase PHLPP with AKT,
thereby promoting cell growth and chemotherapy desensitization. These
observations broaden our understanding of chemotherapy response and have
important implications for the selection of targeted therapies in a cell context
dependent manner. EGFR inhibition can only sensitize EGFR-high cells for
chemotherapy, while AKT inhibition increases chemosensitivity in EGFR-low cells.
By understanding these mechanisms, we can take advantage of the cellular context
to individualize antineoplastic therapy. Finally, our data also suggest targeting
of EFFRI1 in EGFR-low cancer as a promising therapeutic approach.
PMID- 29335248
TI - Fast neurogenesis from carotid body quiescent neuroblasts accelerates adaptation
to hypoxia.
AB - Unlike other neural peripheral organs, the adult carotid body (CB) has a
remarkable structural plasticity, as it grows during acclimatization to hypoxia.
The CB contains neural stem cells that can differentiate into oxygen-sensitive
glomus cells. However, an extended view is that, unlike other catecholaminergic
cells of the same lineage (sympathetic neurons or chromaffin cells), glomus cells
can divide and thus contribute to CB hypertrophy. Here, we show that O2-sensitive
mature glomus cells are post-mitotic. However, we describe an unexpected
population of pre-differentiated, immature neuroblasts that express
catecholaminergic markers and contain voltage-dependent ion channels, but are
unresponsive to hypoxia. Neuroblasts are quiescent in normoxic conditions, but
rapidly proliferate and differentiate into mature glomus cells during hypoxia.
This unprecedented "fast neurogenesis" is stimulated by ATP and acetylcholine
released from mature glomus cells. CB neuroblasts, which may have evolved to
facilitate acclimatization to hypoxia, could contribute to the CB oversensitivity
observed in highly prevalent human diseases.
PMID- 29335249
TI - Hypertension and Diabetes Mellitus: Coprediction and Time Trajectories.
AB - Type 2 diabetes mellitus and hypertension overlap in the population. In many
subjects, development of diabetes mellitus is characterized by a relatively rapid
increase in plasma glucose values. Whether a similar phenomenon occurs during the
development of hypertension is not known. We analyzed the pattern of blood
pressure (BP) changes during the development of hypertension in patients with or
without diabetes mellitus using data from the MCDS (Mexico City Diabetes Study; a
population-based study of diabetes mellitus in Hispanic whites) and in the FOS
(Framingham Offspring Study, a community-based study in non-Hispanic whites)
during a 7-year follow-up. Diabetes mellitus at baseline was a significant
predictor of incident hypertension (in FOS, odds ratio, 3.14; 95% confidence
interval, 2.17-4.54) independently of sex, age, body mass index, and familial
diabetes mellitus. Conversely, hypertension at baseline was an independent
predictor of incident diabetes mellitus (in FOS, odds ratio, 3.33; 95% CI, 2.50
4.44). In >60% of the converters, progression from normotension to hypertension
was characterized by a steep increase in BP values, averaging 20 mm Hg for
systolic BP within 3.5 years (in MCDS). In comparison with the nonconverters
group, hypertension and diabetes mellitus converters shared a metabolic syndrome
phenotype (hyperinsulinemia, higher body mass index, waist girth, BP, heart rate
and pulse pressure, and dyslipidemia). Overall, results were similar in the 2
ethnic groups. We conclude that (1) development of hypertension and diabetes
mellitus track each other over time, (2) transition from normotension to
hypertension is characterized by a sharp increase in BP values, and (3) insulin
resistance is one common feature of both prediabetes and prehypertension and an
antecedent of progression to 2 respective disease states.
PMID- 29335250
TI - Akap1 Regulates Vascular Function and Endothelial Cells Behavior.
AB - MitoAKAPs (mitochondrial A kinase anchoring proteins), encoded by the Akap1 gene,
regulate multiple cellular processes governing mitochondrial homeostasis and cell
viability. Although mitochondrial alterations have been associated to endothelial
dysfunction, the role of mitoAKAPs in the vasculature is currently unknown. To
test this, postischemic neovascularization, vascular function, and arterial blood
pressure were analyzed in Akap1 knockout mice (Akap1-/- ) and their wild-type
(wt) littermates. Primary cultures of aortic endothelial cells (ECs) were also
obtained from Akap1-/- and wt mice, and ECs migration, proliferation, survival,
and capillary-like network formation were analyzed under different experimental
conditions. After femoral artery ligation, Akap1-/- mice displayed impaired blood
flow and functional recovery, reduced skeletal muscle capillary density, and Akt
phosphorylation compared with wt mice. In Akap1-/- ECs, a significant enhancement
of hypoxia-induced mitophagy, mitochondrial dysfunction, reactive oxygen species
production, and apoptosis were observed. Consistently, capillary-like network
formation, migration, proliferation, and AKT phosphorylation were reduced in
Akap1-/- ECs. Alterations in Akap1-/- ECs behavior were also confirmed in Akap1-/
mice, which exhibited a selective reduction in acetylcholine-induced
vasorelaxation in mesenteric arteries and a mild but significant increase in
arterial blood pressure levels compared with wt. Finally, overexpression of a
constitutively active Akt mutant restored vascular reactivity and ECs function in
Akap1-/- conditions. These results demonstrate the important role of mitoAKAPs in
the modulation of multiple ECs functions in vivo and in vitro, suggesting that
mitochondria-dependent regulation of ECs might represent a novel therapeutic
approach in cardiovascular diseases characterized by endothelial dysfunction.
PMID- 29335251
TI - Goblet cell carcinomas of the appendix: rare but aggressive neoplasms with
challenging management.
AB - Goblet cell carcinomas (GCC) are a rare, aggressive sub-type of appendiceal
tumours with neuroendocrine features, and controversy exists with regards to
therapeutic strategy. We undertook a retrospective review of GCC patients
surgically treated at two tertiary referral centres. Clinical and
histopathological data were extracted from a prospectively maintained database.
Survival analyses utilised Kaplan-Meier methodology. Twenty-one patients were
identified (9 females). Median age at diagnosis was 55 years (range 32-77). There
were 3, 6 and 9 grade 1, 2 and 3 tumours, respectively. One, 10, 5 and 5 patients
had stage I, II, III and IV disease at diagnosis, respectively. There were 8, 10
and 3 Tang class A, B and C tumours, respectively. Index operation was
appendectomy (n = 12), right hemicolectomy (n = 6) or resections including
appendix/right colon, omentum and the gynaecological system (n = 3). Eight
patients underwent completion right hemicolectomy. Surgery for recurrence
included small bowel resection (n = 2), debulking with peritonectomy and heated
intraperitoneal chemotherapy, and hysterectomy and bilateral salpingo
oophorectomy (all n = 1). Median follow-up was 30 months (range 2.5-123). One-, 3
and 5-year OS was 79.4, 60 and 60%, respectively. Mean OS (1-, 3-, and 5-year
OS) for Tang class A, B and C tumours were 73.1 months (85.7, 85.7, 51.4%), 83.7
months (all 66.7%) and 28.5 months (66.7, 66.7%, not reached), respectively.
Chromogranin A/B and 68Ga-DOTATATE PET/CT were not useful in follow-up, but CEA,
CA 19-9, CA 125 and 18F-FDG PET/CT identified tumour recurrence. GCC must be
clearly discriminated from relatively indolent appendiceal neuroendocrine
neoplasms. 18F-FDG PET/CT and CEA/CA19-9/CA 125 are useful in detecting
recurrence of GCC.
PMID- 29335253
TI - Women's reproductive factors and incident cardiovascular disease in the UK
Biobank.
AB - BACKGROUND: Studies have suggested that women's reproductive factors are
associated with the risk of cardiovascular disease (CVD); however, findings are
mixed. We assessed the relationship between reproductive factors and incident CVD
in the UK Biobank. METHODS: Between 2006 and 2010, the UK Biobank recruited over
500 000 participants aged 40-69 years across the UK. During 7 years of follow-up,
9054 incident cases of CVD (34% women), 5782 cases of coronary heart disease
(CHD) (28% women), and 3489 cases of stroke (43% women) were recorded among 267
440 women and 215 088 men without a history of CVD at baseline. Cox regression
models yielded adjusted hazard ratios (HRs) for CVD, CHD and stroke associated
with reproductive factors. RESULTS: Adjusted HRs (95% CI) for CVD were 1.10 (1.01
to 1.30) for early menarche (<12 years), 0.97 (0.96 to 0.98) for each year
increase in age at first birth, 1.04 (1.00 to 1.09) for each miscarriage, 1.14
(1.02 to 1.28) for each stillbirth, and 1.33 (1.19 to 1.49) for early menopause
(<47 years). Hysterectomy without oophorectomy or with previous oophorectomy had
adjusted HRs of 1.16 (1.06 to 1.28) and 2.30 (1.20 to 4.43) for CVD. Each
additional child was associated with a HR for CVD of 1.03 (1.00 to 1.06) in women
and 1.03 (1.02 to 1.05) in men. CONCLUSIONS: Early menarche, early menopause,
earlier age at first birth, and a history of miscarriage, stillbirth or
hysterectomy were each independently associated with a higher risk of CVD in
later life. The relationship between the number of children and incident CVD was
similar for men and women.
PMID- 29335252
TI - Diagnostic re-evaluation of congenital hypothyroidism in Macedonia: predictors
for transient or permanent hypothyroidism.
AB - BACKGROUND: Diagnostic re-evaluation is important for all patients with
congenital hypothyroidism (CH) for determining the etiology and identifying
transient CH cases. Our study is a first thyroxine therapy withdrawal study
conducted in Macedonian CH patients for a diagnostic re-evaluation. We aimed to
evaluate the etiology of CH, the prevalence of transient CH and identify
predictive factors for distinguishing between permanent (PCH) and transient CH
(TCH). MATERIALS AND METHODS: Patients with CH aged >3 years underwent a trial of
treatment withdrawal for 4 weeks period. Thyroid function testing (TFT),
ultrasound and Technetium-99m pertechnetate thyroid scan were performed
thereafter. TCH was defined when TFT remained within normal limits for at least 6
month follow-up. PCH was diagnosed when TFT was abnormal and classified according
the imaging findings. RESULTS: 42 (55%) patients had PCH and 34 (45.0%) patients
had TCH. Thyroid agenesia was the most prevalent form in the PCH group. Patients
with TCH had lower initial thyroid-stimulating hormone (TSH) values (P < 0.0001);
higher serum thyroxine levels (P = 0.0023) and lower mean doses of levothyroxine
during treatment period (P < 0.0001) than patients with PCH. Initial TSH level
<30.5 IU/mL and levothyroxine dose at 3 years of age <2.6 mg/kg/day were a
significant predictive factors for TCH; sensitivity 92% and 100%, specificity
75.6% and 76%, respectively. CONCLUSION: TCH presents a significant portion of
patients with CH. Initial TSH value and levothyroxine dose during treatment
period has a predictive role in differentiating TCH from PCH. Earlier re
evaluation, between 2 and 3 years age might be considered in some patients
requiring low doses of levothyroxine.
PMID- 29335254
TI - Depressed left and right ventricular cardiac output in fetuses of diabetic
mothers.
AB - INTRODUCTION: We compared right and left ventricular cardiac output (RVCO and
LVCO) in fetuses of diabetic mothers (FDM) to a large normal cohort. METHODS: We
prospectively enrolled 264 normal fetuses and 30 FDM. Fetal CO parameters:
semilunar valve velocity time integrals (AVVTI, PVVTI), ventricular outflow
diameters (LVOTD, RVOTD), stroke volumes (AVSV, PVSV) were measured, and LVCO and
RVCO calculated. These were normalized using nonlinear regression to estimated
fetal weight (EFW) to provide means and standard deviations. Among FDMs, mean Z
scores and 95% confidence limits (CL) were calculated, and compared to zero.
RESULTS: LVCO, RVCO, and parameters they were calculated from, increased
predictably and non-linearly with increasing EFW. In FDM, LVCO was depressed
(mean Z -1.679, 95% CL -2.404, -0.955, p<0.001), and AVVTI, LVOTD, AVSV
significantly lower than normal. Similarly, RVCO (mean Z = -1.119, CL -1.839,
0.400, p=0.003), RVOTD (mean -2.085, CL -3.077, -1.093, p<0.001), and PVSV (mean
1.184, CL -1.921, -0.446, p=0.003) were lower than normal, however, PVVTI was not
different (mean Z 0.078, CL -0.552, +0.707, p=0.803). CONCLUSION: Normal
biventricular stroke volumes and outputs follow a nonlinear regression with EFW.
FDM have significantly lower right and left heart stroke volumes and outputs for
weight than do normal fetuses.
PMID- 29335255
TI - Neighbourhood looking glass: 360o automated characterisation of the built
environment for neighbourhood effects research.
AB - BACKGROUND: Neighbourhood quality has been connected with an array of health
issues, but neighbourhood research has been limited by the lack of methods to
characterise large geographical areas. This study uses innovative computer vision
methods and a new big data source of street view images to automatically
characterise neighbourhood built environments. METHODS: A total of 430 000 images
were obtained using Google's Street View Image API for Salt Lake City, Chicago
and Charleston. Convolutional neural networks were used to create indicators of
street greenness, crosswalks and building type. We implemented log Poisson
regression models to estimate associations between built environment features and
individual prevalence of obesity and diabetes in Salt Lake City, controlling for
individual-level and zip code-level predisposing characteristics. RESULTS:
Computer vision models had an accuracy of 86%-93% compared with manual
annotations. Charleston had the highest percentage of green streets (79%), while
Chicago had the highest percentage of crosswalks (23%) and commercial
buildings/apartments (59%). Built environment characteristics were categorised
into tertiles, with the highest tertile serving as the referent group.
Individuals living in zip codes with the most green streets, crosswalks and
commercial buildings/apartments had relative obesity prevalences that were 25%
28% lower and relative diabetes prevalences that were 12%-18% lower than
individuals living in zip codes with the least abundance of these neighbourhood
features. CONCLUSION: Neighbourhood conditions may influence chronic disease
outcomes. Google Street View images represent an underused data resource for the
construction of built environment features.
PMID- 29335257
TI - Staphylococcal Superantigens Use LAMA2 as a Coreceptor To Activate T Cells.
AB - Canonical Ag-dependent TCR signaling relies on activation of the src-family
tyrosine kinase LCK. However, staphylococcal superantigens can trigger TCR
signaling by activating an alternative pathway that is independent of LCK and
utilizes a Galpha11-containing G protein-coupled receptor (GPCR) leading to
PLCbeta activation. The molecules linking the superantigen to GPCR signaling are
unknown. Using the ligand-receptor capture technology LRC-TriCEPS, we identified
LAMA2, the alpha2 subunit of the extracellular matrix protein laminin, as the
coreceptor for staphylococcal superantigens. Complementary binding assays (ELISA,
pull-downs, and surface plasmon resonance) provided direct evidence of the
interaction between staphylococcal enterotoxin E and LAMA2. Through its G4
domain, LAMA2 mediated the LCK-independent T cell activation by these toxins.
Such a coreceptor role of LAMA2 involved a GPCR of the calcium-sensing receptor
type because the selective antagonist NPS 2143 inhibited superantigen-induced T
cell activation in vitro and delayed the effects of toxic shock syndrome in vivo.
Collectively, our data identify LAMA2 as a target of antagonists of
staphylococcal superantigens to treat toxic shock syndrome.
PMID- 29335256
TI - Recombinant Human Vimentin Binds to P-Selectin and Blocks Neutrophil Capture and
Rolling on Platelets and Endothelium.
AB - Leukocyte adhesion to vascular endothelium and platelets is an early step in the
acute inflammatory response. The initial process is mediated through P-selectin
glycoprotein ligand-1 (PSGL-1) on leukocytes binding to platelets adhered to
endothelium and the endothelium itself via P-selectin. Although these
interactions are generally beneficial, pathologic inflammation may occur in
undesirable circumstances, such as in acute lung injury (ALI) and ischemia and
reperfusion injury. Therefore, the development of novel therapies to attenuate
inflammation may be beneficial. In this article, we describe the potential
benefit of using a recombinant human vimentin (rhVim) on reducing human leukocyte
adhesion to vascular endothelium and platelets under shear stress. The addition
of rhVim to whole blood and isolated neutrophils decreased leukocyte adhesion to
endothelial and platelet monolayers. Furthermore, rhVim blocked neutrophil
adhesion to P-selectin-coated surfaces. Binding assays showed that rhVim binds
specifically to P-selectin and not to its counterreceptor, PSGL-1. Finally, in an
endotoxin model of ALI in C57BL/6J mice, treatment with rhVim significantly
decreased histologic findings of ALI. These data suggest a potential role for
rhVim in attenuating inflammation through blocking P-selectin-PSGL-1
interactions.
PMID- 29335258
TI - Cleavage of TL1A Differentially Regulates Its Effects on Innate and Adaptive
Immune Cells.
AB - TNF superfamily cytokines play major roles in the regulation of adaptive and
innate immunity. The TNF superfamily cytokine TL1A (TNFSF15), through its cognate
receptor DR3 (TNFRSF25), promotes T cell immunity to pathogens and directly
costimulates group 2 and 3 innate lymphoid cells. Polymorphisms in the TNFSF15
gene are associated with the risk for various human diseases, including
inflammatory bowel disease. Like other cytokines in the TNF superfamily, TL1A is
synthesized as a type II transmembrane protein and cleaved from the plasma
membrane by metalloproteinases. Membrane cleavage has been shown to alter or
abrogate certain activities of other TNF family cytokines; however, the
functional capabilities of membrane-bound and soluble forms TL1A are not known.
Constitutive expression of TL1A in transgenic mice results in expansion of
activated T cells and promotes intestinal hyperplasia and inflammation through
stimulation of group 2 innate lymphoid cells. Through the generation of membrane
restricted TL1A-transgenic mice, we demonstrate that membrane TL1A promotes
expression of inflammatory cytokines in the lung, dependent upon DR3 expression
on T cells. Soluble TL1A alone was unable to produce this phenotype but was still
able to induce intestinal type 2 inflammation independently of T cells. These
data suggest differential roles for membrane and soluble TL1A on adaptive and
innate immune cells and have implications for the consequences of blocking these
two forms of TL1A.
PMID- 29335259
TI - Mental health needs our attention.
PMID- 29335260
TI - An emergency response to the opioid overdose crisis in Canada: a regulated opioid
distribution program.
PMID- 29335262
TI - Addressing overestimation of the prevalence of depression based on self-report
screening questionnaires.
PMID- 29335261
TI - Childhood trajectories of peer victimization and prediction of mental health
outcomes in midadolescence: a longitudinal population-based study.
AB - BACKGROUND: Exposure to peer victimization is relatively common. However, little
is known about its developmental course and its effect on impairment associated
with mental illnesses. We aimed to identify groups of children following
differential trajectories of peer victimization from ages 6 to 13 years and to
examine predictive associations of these trajectories with mental health in
adolescence. METHODS: Participants were members of the Quebec Longitudinal Study
of Child Development, a prospective cohort of 2120 children born in 1997/98 who
were followed until age 15 years. We included 1363 participants with self
reported victimization from ages 6 to 13 years and data available on their mental
health status at 15 years. RESULTS: We identified 3 trajectories of peer
victimization. The 2 prevailing groups were participants with little or moderate
exposure to victimization (441/1685 [26.2%] and 1000/1685 [59.3%], respectively);
the third group (244 [14.5%]) had been chronically exposed to the most severe and
long-lasting levels of victimization. The most severely victimized individuals
had greater odds of reporting debilitating depressive or dysthymic symptoms (odds
ratio [OR] 2.56, 95% confidence interval [CI] 1.27-5.17), debilitating
generalized anxiety problems (OR 3.27, CI 1.64-6.51) and suicidality (OR 3.46, CI
1.53-7.81) at 15 years than those exposed to the lowest levels of victimization,
after adjustment for sex, childhood mental health, family hardship and
victimization perpetration. The association with suicidality remained significant
after controlling for concurrent symptoms of depression or dysthymia and
generalized anxiety problems. INTERPRETATION: Adolescents who were most severely
victimized by peers had an increased risk of experiencing severe symptoms
consistent with mental health problems. Given that peer victimization
trajectories are established early on, interventions to reduce the risk of being
victimized should start before enrolment in the formal school system.
PMID- 29335263
TI - Exacerbation of psychosis triggered by a synthetic cannabinoid in a 70-year-old
woman with Parkinson disease.
PMID- 29335264
TI - Physician burnout.
PMID- 29335265
TI - Contact lens-related Pseudomonas aeruginosa keratitis in a 49-year-old woman.
PMID- 29335266
TI - Urgent care access: finding solutions that match causation.
PMID- 29335268
TI - Fertility advocates protest criminal sanctions in assisted reproduction act.
PMID- 29335267
TI - Peripartum suicide: additional considerations.
PMID- 29335269
TI - Family doctors call for guaranteed access to EMR data for research and quality
improvement.
PMID- 29335270
TI - Doctors disappointed by income sprinkling changes.
PMID- 29335271
TI - Health and social care: What's in a name?
PMID- 29335272
TI - Complementary Value of Cardiac Magnetic Resonance Imaging and Positron Emission
Tomography/Computed Tomography in the Assessment of Cardiac Sarcoidosis.
AB - BACKGROUND: Although cardiac magnetic resonance (CMR) and positron emission
tomography (PET) detect different pathological attributes of cardiac sarcoidosis
(CS), the complementary value of these tests has not been evaluated. Our
objective was to determine the value of combining CMR and PET in assessing the
likelihood of CS and guiding patient management. METHODS AND RESULTS: In this
retrospective study, we included 107 consecutive patients referred for evaluation
of CS by both CMR and PET. Two experienced readers blinded to all clinical data
reviewed CMR and PET images and categorized the likelihood of CS as no (<10%),
possible (10%-50%), probable (50%-90%), or highly probable(>90%) based on
predefined criteria. Patient management after imaging was assessed for all
patients and across categories of increasing CS likelihood. A final clinical
diagnosis for each patient was assigned based on a subsequent review of all
available imaging, clinical, and pathological data. Among 107 patients (age, 55+/
11 years; left ventricular ejection fraction, 43+/-16%), 91 (85%) had late
gadolinium enhancement, whereas 82 (76%) had abnormal F18-fluorodeoxyglucose
uptake on PET, suggesting active inflammation. Among the 91 patients with
positive late gadolinium enhancement, 60 (66%) had abnormal F18
fluorodeoxyglucose uptake. When PET data were added to CMR, 48 (45%) patients
were reclassified as having a higher or lower likelihood of CS, most of them
(80%) being correctly reclassified when compared with the final diagnosis.
Changes in immunosuppressive therapies were significantly more likely among
patients with highly probable CS. CONCLUSIONS: Among patients with suspected CS,
combining CMR and PET provides complementary value for estimating the likelihood
of CS and guiding patient management.
PMID- 29335273
TI - Establishing an Evidence-Based Method to Diagnose Cardiac Sarcoidosis: The
Complementary Use of Cardiac Magnetic Resonance Imaging and FDG-PET.
PMID- 29335274
TI - Doctors from overseas are missing out on dyslexia screening, researchers find.
PMID- 29335275
TI - Interplay between ChREBP and SREBP-1c coordinates postprandial glycolysis and
lipogenesis in livers of mice.
AB - Lipogenesis in liver is highest in the postprandial state; insulin activates
SREBP-1c, which transcriptionally activates genes involved in FA synthesis,
whereas glucose activates carbohydrate-responsive element-binding protein
(ChREBP), which activates both glycolysis and FA synthesis. Whether SREBP-1c and
ChREBP act independently of one another is unknown. Here, we characterized mice
with liver-specific deletion of ChREBP (L-Chrebp-/- mice). Hepatic ChREBP
deficiency resulted in reduced mRNA levels of glycolytic and lipogenic enzymes,
particularly in response to sucrose refeeding following fasting, a dietary
regimen that elicits maximal lipogenesis. mRNA and protein levels of SREBP-1c, a
master transcriptional regulator of lipogenesis, were also reduced in L-Chrebp-/-
livers. Adeno-associated virus-mediated restoration of nuclear SREBP-1c in L
Chrebp-/- mice normalized expression of a subset of lipogenic genes, while not
affecting glycolytic genes. Conversely, ChREBP overexpression alone failed to
support expression of lipogenic genes in the livers of mice lacking active SREBPs
as a result of Scap deficiency. Together, these data show that SREBP-1c and
ChREBP are both required for coordinated induction of glycolytic and lipogenic
mRNAs. Whereas SREBP-1c mediates insulin's induction of lipogenic genes, ChREBP
mediates glucose's induction of both glycolytic and lipogenic genes. These
overlapping, but distinct, actions ensure that the liver synthesizes FAs only
when insulin and carbohydrates are both present.
PMID- 29335277
TI - Adverse effects of caffeinated energy drinks among youth and young adults in
Canada: a Web-based survey.
AB - BACKGROUND: Energy drink consumption has increased dramatically among young
Canadians, with anecdotal evidence of adverse health effects. There is a lack of
population-based studies to examine the prevalence of adverse events from energy
drinks, particularly among young people. The current study sought to assess
adverse events from energy drinks among a population-based sample of youth and
young adults in Canada. METHODS: An online survey was conducted in 2015 with a
national sample of youth (aged 12-17 yr) and young adults (aged 18-24 yr)
recruited from a consumer panel. Respondents reported prior consumption of energy
drinks as well as adverse outcomes, concurrent activities associated with the
outcomes and whether medical attention was sought or considered. Adverse events
from coffee were also assessed for comparison. Weighted analyses are reported.
RESULTS: Of the 2055 respondents, 1516 (73.8%) reported having ever consumed an
energy drink, and 1741 (84.7%) reported having ever consumed coffee (unweighted).
Overall, 55.4% of respondents who had ever consumed an energy drink reported that
they had experienced at least 1 adverse event, including fast heartbeat (24.7%),
difficulty sleeping (24.1%), headache (18.3%), nausea/vomiting/diarrhea (5.1%),
chest pain (3.6%) and seizures (0.2%); 3.1% had sought or had considered seeking
medical help for an adverse event. The prevalence of reported adverse events was
significantly greater among energy drink consumers than among coffee consumers
(36.0%) (odds ratio [OR] 2.67 [95% confidence interval (CI) 2.01-2.56]), as was
the proportion who reported seeking or considering seeking medical help for
adverse events (3.1% v. 1.4%) (OR 2.18 [95% CI 1.39-3.41]). INTERPRETATION: More
than half of youth and young adults who had consumed energy drinks reported
adverse outcomes, some serious enough to warrant seeking medical help. The
adverse outcomes were consistent with the physiologic effects of caffeine but
were significantly more prevalent than with other sources of caffeine such as
coffee, consistent with data from national adverse event databases.
PMID- 29335278
TI - Coffee consumption and health: we need randomised controlled trials.
PMID- 29335276
TI - Assigning function to natural allelic variation via dynamic modeling of gene
network induction.
AB - More and more natural DNA variants are being linked to physiological traits. Yet,
understanding what differences they make on molecular regulations remains
challenging. Important properties of gene regulatory networks can be captured by
computational models. If model parameters can be "personalized" according to the
genotype, their variation may then reveal how DNA variants operate in the
network. Here, we combined experiments and computations to visualize natural
alleles of the yeast GAL3 gene in a space of model parameters describing the
galactose response network. Alleles altering the activation of Gal3p by galactose
were discriminated from those affecting its activity (production/degradation or
efficiency of the activated protein). The approach allowed us to correctly
predict that a non-synonymous SNP would change the binding affinity of Gal3p with
the Gal80p transcriptional repressor. Our results illustrate how personalizing
gene regulatory models can be used for the mechanistic interpretation of genetic
variants.
PMID- 29335279
TI - Margaret McCartney: We need another vote.
PMID- 29335282
TI - Treatment of Subclinical Atrial Fibrillation: Does One Plus One Always Equal Two?
PMID- 29335283
TI - Confusion Around Therapeutic Temperature Management Hypothermia After In-Hospital
Cardiac Arrest?
PMID- 29335284
TI - Nitric Oxide Signaling and Atherothrombosis Redux: Evidence From Experiments of
Nature and Implications for Therapy.
PMID- 29335280
TI - Mapping protein interactions of sodium channel NaV1.7 using epitope-tagged gene
targeted mice.
AB - The voltage-gated sodium channel NaV1.7 plays a critical role in pain pathways.
We generated an epitope-tagged NaV1.7 mouse that showed normal pain behaviours to
identify channel-interacting proteins. Analysis of NaV1.7 complexes affinity
purified under native conditions by mass spectrometry revealed 267 proteins
associated with Nav1.7 in vivo The sodium channel beta3 (Scn3b), rather than the
beta1 subunit, complexes with Nav1.7, and we demonstrate an interaction between
collapsing-response mediator protein (Crmp2) and Nav1.7, through which the
analgesic drug lacosamide regulates Nav1.7 current density. Novel NaV1.7 protein
interactors including membrane-trafficking protein synaptotagmin-2 (Syt2), L-type
amino acid transporter 1 (Lat1) and transmembrane P24-trafficking protein 10
(Tmed10) together with Scn3b and Crmp2 were validated by co-immunoprecipitation
(Co-IP) from sensory neuron extract. Nav1.7, known to regulate opioid receptor
efficacy, interacts with the G protein-regulated inducer of neurite outgrowth
(Gprin1), an opioid receptor-binding protein, demonstrating a physical and
functional link between Nav1.7 and opioid signalling. Further information on
physiological interactions provided with this normal epitope-tagged mouse should
provide useful insights into the many functions now associated with the NaV1.7
channel.
PMID- 29335281
TI - High-throughput identification of RNA nuclear enrichment sequences.
AB - In the post-genomic era, thousands of putative noncoding regulatory regions have
been identified, such as enhancers, promoters, long noncoding RNAs (lncRNAs), and
a cadre of small peptides. These ever-growing catalogs require high-throughput
assays to test their functionality at scale. Massively parallel reporter assays
have greatly enhanced the understanding of noncoding DNA elements en masse Here,
we present a massively parallel RNA assay (MPRNA) that can assay 10,000 or more
RNA segments for RNA-based functionality. We applied MPRNA to identify RNA-based
nuclear localization domains harbored in lncRNAs. We examined a pool of 11,969
oligos densely tiling 38 human lncRNAs that were fused to a cytosolic transcript.
After cell fractionation and barcode sequencing, we identified 109 unique RNA
regions that significantly enriched this cytosolic transcript in the nucleus
including a cytosine-rich motif. These nuclear enrichment sequences are highly
conserved and over-represented in global nuclear fractionation sequencing.
Importantly, many of these regions were independently validated by single
molecule RNA fluorescence in situ hybridization. Overall, we demonstrate the
utility of MPRNA for future investigation of RNA-based functionalities.
PMID- 29335285
TI - Sodium and Potassium Intake in US Adults.
PMID- 29335286
TI - Biomarker-Assisted Diagnosis of Acute Aortic Dissection.
PMID- 29335287
TI - Identifying Candidates for Advanced Hemodynamic Support After Cardiac Arrest.
PMID- 29335289
TI - Costly Medications Add Urgency to Physician-Patient Affordability Discussions.
PMID- 29335290
TI - Young Male With Incessantly Wide Complex Tachycardia: What Is the Substrate of
the Arrhythmia?
PMID- 29335288
TI - Prognostic Value of High-Sensitivity Troponin T in Chronic Heart Failure: An
Individual Patient Data Meta-Analysis.
AB - BACKGROUND: Most patients with chronic heart failure have detectable troponin
concentrations when evaluated by high-sensitivity assays. The prognostic
relevance of this finding has not been clearly established so far. We aimed to
assess high-sensitivity troponin assay for risk stratification in chronic heart
failure through a meta-analysis approach. METHODS: Medline, EMBASE, Cochrane
Library, and Scopus were searched in April 2017 by 2 independent authors. The
terms were "troponin" AND "heart failure" OR "cardiac failure" OR "cardiac
dysfunction" OR "cardiac insufficiency" OR "left ventricular dysfunction."
Inclusion criteria were English language, clinical stability, use of a high
sensitivity troponin assay, follow-up studies, and availability of individual
patient data after request to authors. Data retrieved from articles and provided
by authors were used in agreement with the PRISMA statement. The end points were
all-cause death, cardiovascular death, and hospitalization for cardiovascular
cause. RESULTS: Ten studies were included, reporting data on 11 cohorts and 9289
patients (age 66+/-12 years, 77% men, 60% ischemic heart failure, 85% with left
ventricular ejection fraction <40%). High-sensitivity troponin T data were
available for all patients, whereas only 209 patients also had high-sensitivity
troponin I assayed. When added to a prognostic model including established risk
markers (sex, age, ischemic versus nonischemic etiology, left ventricular
ejection fraction, estimated glomerular filtration rate, and N-terminal fraction
of pro-B-type natriuretic peptide), high-sensitivity troponin T remained
independently associated with all-cause mortality (hazard ratio, 1.48; 95%
confidence interval, 1.41-1.55), cardiovascular mortality (hazard ratio, 1.40;
95% confidence interval, 1.33-1.48), and cardiovascular hospitalization (hazard
ratio, 1.42; 95% confidence interval, 1.36-1.49), over a median 2.4-year follow
up (all P<0.001). High-sensitivity troponin T significantly improved risk
prediction when added to a prognostic model including the variables above. It
also displayed an independent prognostic value for all outcomes in almost all
population subgroups. The area under the curve-derived 18 ng/L cutoff yielded
independent prognostic value for the 3 end points in both men and women, patients
with either ischemic or nonischemic etiology, and across categories of renal
dysfunction. CONCLUSIONS: In chronic heart failure, high-sensitivity troponin T
is a strong and independent predictor of all-cause and cardiovascular mortality,
and of hospitalization for cardiovascular causes, as well. This biomarker then
represents an additional tool for prognostic stratification.
PMID- 29335292
TI - Letter by Madias Regarding Article, "Prosthetic Valve Endocarditis After Surgical
Aortic Valve Replacement".
PMID- 29335291
TI - Electronic Cigarette Smoking Increases Arterial Stiffness and Oxidative Stress to
a Lesser Extent Than a Single Conventional Cigarette: An Acute and Chronic Study.
PMID- 29335293
TI - Response by Glaser et al to Letter Regarding Article, "Prosthetic Valve
Endocarditis After Surgical Aortic Valve Replacement".
PMID- 29335294
TI - Letter by Jin-shan and Xue-bin Regarding Article, "Prospective Study of Adenosine
on Atrioventricular Nodal Conduction in Pediatric and Young Adult Patients After
Heart Transplantation".
PMID- 29335295
TI - Letter by Ye et al Regarding Article, "Prospective Study of Adenosine on
Atrioventricular Nodal Conduction in Pediatric and Young Adult Patients After
Heart Transplantation".
PMID- 29335296
TI - Digital healthcare: regulating the revolution.
PMID- 29335297
TI - The apps attempting to transfer NHS 111 online.
PMID- 29335298
TI - Crystal structure of IspF from Bacillus subtilis and absence of protein complex
assembly amongst IspD/IspE/IspF enzymes in the MEP pathway.
AB - 2-C-Methyl-d-erythritol 2,4-cyclodiphosphate synthase (IspF) is a key enzyme in
the 2-C-Methyl-d-erythritol-4-phosphate (MEP) pathway of isoprenoid biosynthesis.
This enzyme catalyzes the 4-diphosphocytidyl-2-C-methyl-d-erythritol 2-phosphate
(CDPME2P) to 2-C-methyl-d-erythritol 2,4-cyclodiphosphate (MEcDP) with
concomitant release of cytidine 5'-diphospate (CMP). Bacillus subtilis is a
potential host cell for the production of isoprenoids, but few studies are
performed on the key enzymes of MEP pathway in B. subtilis In this work, the high
resolution crystal structures of IspF in native and complex with CMP from B.
subtilis have been determined. Structural comparisons indicate that there is a
looser packing of the subunits of IspF in B. subtilis, whereas the solvent
accessible surface of its active pockets is smaller than that in Escherichia
coli. Meanwhile, the protein-protein associations of 2-C-Methyl-d-erythritol-4
phosphatecytidyltransferase (IspD), CDPME kinase (IspE) and IspF from B. subtilis
and E. coli, which catalyze three consecutive steps in the MEP pathway, are
analyzed by native gel shift and size exclusion chromatography methods. The data
here show that protein complex assembly is not detectable. These results will be
useful for isoprenoid biosynthesis by metabolic engineering.
PMID- 29335299
TI - HOTAIR contributes to cell proliferation and metastasis of cervical cancer via
targetting miR-23b/MAPK1 axis.
AB - The long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) has been
found to be overexpressed in many human malignancies and involved in tumor
progression and metastasis. Although the downstream target through which HOTAIR
modulates tumor metastasis is not well-known, evidence suggests that miR-23b
might be involved in this event. In the present study, the expressions of HOTAIR
and miR-23b were detected by real-time PCR in 33 paired cervical cancer tissue
samples and cervical cell lines. The effects of HOTAIR on the expressions of miR
23b and mitogen-activated protein kinase 1 (MAPK1) were studied by overexpression
and RNAi approaches. We found that HOTAIR expression was significantly increased
in cervical cancer cells and tissues. In contrast, the expression of miR-23b was
obviously decreased. We further demonstrated that HOTAIR knockdown promoted
apoptosis and inhibited cell proliferation and invasion in vitro and in vivo
Moreover, our data indicated that HOTAIR may competitively bind miR-23b and
modulate the expression of MAPK1 indirectly in cervical cancer cells. Taken
together, our study has identified a novel pathway through which HOTAIR exerts
its oncogenic role, and provided a molecular basis for potential applications of
HOTAIR in the prognosis and treatment of cervical cancer.
PMID- 29335303
TI - Trump administration allows states to deny Medicaid to unemployed people.
PMID- 29335301
TI - Mobilization of a splicing factor through a nuclear kinase-kinase complex.
AB - The splicing of mRNA is dependent on serine-arginine (SR) proteins that are
mobilized from membrane-free, nuclear speckles to the nucleoplasm by the Cdc2
like kinases (CLKs). This movement is critical for SR protein-dependent assembly
of the macromolecular spliceosome. Although CLK1 facilitates such trafficking
through the phosphorylation of serine-proline dipeptides in the prototype SR
protein SRSF1, an unrelated enzyme known as SR protein kinase 1 (SRPK1) performs
the same function but does not efficiently modify these dipeptides in SRSF1. We
now show that the ability of SRPK1 to mobilize SRSF1 from speckles to the
nucleoplasm is dependent on active CLK1. Diffusion from speckles is promoted by
the formation of an SRPK1-CLK1 complex that facilitates dissociation of SRSF1
from CLK1 and enhances the phosphorylation of several serine-proline dipeptides
in this SR protein. Down-regulation of either kinase blocks EGF-stimulated
mobilization of nuclear SRSF1. These findings establish a signaling pathway that
connects SRPKs to SR protein activation through the associated CLK family of
kinases.
PMID- 29335300
TI - Extracellular ATP activates store-operated Ca2+ entry in white adipocytes:
functional evidence for STIM1 and ORAI1.
AB - In the present study, we have applied ratiometric measurements of intracellular
Ca2+ concentrations ([Ca2+]i) to show that extracellularly applied ATP (adenosine
triphosphate) (100 uM) stimulates store-operated Ca2+ entry (SOCE) in 3T3-L1
adipocytes. ATP produced a rapid increase in [Ca2+]i consisting of an initial
transient elevation followed by a sustained elevated phase that could be observed
only in the presence of extracellular Ca2+ Gene expression data and [Ca2+]i
recordings with uridine-5'-triphosphate or with the phospholipase C (PLC)
inhibitor U73122 demonstrated the involvement of purinergic P2Y2 receptors and
the PLC/inositol trisphosphate pathway. The [Ca2+]i elevation produced by
reintroduction of a Ca2+-containing intracellular solution to adipocytes exposed
to ATP in the absence of Ca2+ was diminished by known SOCE antagonists. The chief
molecular components of SOCE, the stromal interaction molecule 1 (STIM1) and the
calcium release-activated calcium channel protein 1 (ORAI1), were detected at the
mRNA and protein level. Moreover, SOCE was largely diminished in cells where
STIM1 and/or ORAI1 had been silenced by small interfering (si)RNA. We conclude
that extracellular ATP activates SOCE in white adipocytes, an effect
predominantly mediated by STIM1 and ORAI1.
PMID- 29335304
TI - Differentiating between acute heart failure and acute respiratory distress
syndrome.
PMID- 29335305
TI - Orolingual and abdominal angioedema post thrombolysis and thrombectomy.
PMID- 29335307
TI - Editors' note: A phase 3 trial of IV immunoglobulin for Alzheimer disease.
PMID- 29335306
TI - Pearls & Oy-sters: Family history of Huntington disease disguised a case of
dentatorubral-pallidoluysian atrophy.
PMID- 29335308
TI - Reader response: A phase 3 trial of IV immunoglobulin for Alzheimer disease.
PMID- 29335309
TI - Author response: A phase 3 trial of IV immunoglobulin for Alzheimer disease.
PMID- 29335310
TI - Editors' note: Clinical Reasoning: Labyrinthine hemorrhage: An unusual etiology
for peripheral vertigo.
PMID- 29335311
TI - Reader response: Clinical Reasoning: Labyrinthine hemorrhage: An unusual etiology
for peripheral vertigo.
PMID- 29335312
TI - Author response: Clinical Reasoning: Labyrinthine hemorrhage: An unusual etiology
for peripheral vertigo.
PMID- 29335313
TI - Teaching NeuroImages: Gasperini syndrome.
PMID- 29335314
TI - Teaching Video NeuroImages: Electromyographic variation in stiff-person syndrome.
PMID- 29335315
TI - Teaching Video NeuroImages: Oculogyric crisis in treated Parkinson disease.
PMID- 29335316
TI - Integrated lipid clinics for adults and children with familial
hypercholesterolaemia.
PMID- 29335317
TI - Reduced N-Type Ca2+ Channels in Atrioventricular Ganglion Neurons Are Involved in
Ventricular Arrhythmogenesis.
AB - BACKGROUND: Attenuated cardiac vagal activity is associated with ventricular
arrhythmogenesis and related mortality in patients with chronic heart failure.
Our recent study has shown that expression of N-type Ca2+ channel alpha-subunits
(Cav2.2-alpha) and N-type Ca2+ currents are reduced in intracardiac ganglion
neurons from rats with chronic heart failure. Rat intracardiac ganglia are
divided into the atrioventricular ganglion (AVG) and sinoatrial ganglion.
Ventricular myocardium receives projection of neuronal terminals only from the
AVG. In this study we tested whether a decrease in N-type Ca2+ channels in AVG
neurons contributes to ventricular arrhythmogenesis. METHODS AND RESULTS:
Lentiviral Cav2.2-alpha shRNA (2 MUL, 2*107 pfu/mL) or scrambled shRNA was in
vivo transfected into rat AVG neurons. Nontransfected sham rats served as
controls. Using real-time single-cell polymerase chain reaction and reverse-phase
protein array, we found that in vivo transfection of Cav2.2-alpha shRNA decreased
expression of Cav2.2-alpha mRNA and protein in rat AVG neurons. Whole-cell patch
clamp data showed that Cav2.2-alpha shRNA reduced N-type Ca2+ currents and cell
excitability in AVG neurons. The data from telemetry electrocardiographic
recording demonstrated that 83% (5 out of 6) of conscious rats with Cav2.2-alpha
shRNA transfection had premature ventricular contractions (P<0.05 versus 0% of
nontransfected sham rats or scrambled shRNA-transfected rats). Additionally, an
index of susceptibility to ventricular arrhythmias, inducibility of ventricular
arrhythmias evoked by programmed electrical stimulation, was higher in rats with
Cav2.2-alpha shRNA transfection compared with nontransfected sham rats and
scrambled shRNA-transfected rats. CONCLUSIONS: A decrease in N-type Ca2+ channels
in AVG neurons attenuates vagal control of ventricular myocardium, thereby
initiating ventricular arrhythmias.
PMID- 29335318
TI - Longitudinal Effect of Stroke on Cognition: A Systematic Review.
AB - BACKGROUND: Stroke is associated with an increased risk of dementia; however, the
impact of stroke on cognition has been found to be variable, such that stroke
survivors can show decline, remain stable, or revert to baseline cognitive
functioning. Knowing the natural history of cognitive impairment after stroke is
important for intervention. The aim of this systematic review is to investigate
the longitudinal course of cognitive function in stroke survivors. METHODS AND
RESULTS: Three electronic databases (Medline, Embase, PsycINFO) were searched
using OvidSP from inception to July 15, 2016. Longitudinal studies with >=2 time
points of cognitive assessment after stroke were included. In total, 5952
articles were retrieved and 14 were included. There was a trend toward
significant deterioration in cognitive test scores in stroke survivors (8
studies). Cognitive stability (3 studies) and improvement (3 studies) were also
demonstrated, although follow-up time tended to be shorter in these studies.
Variables associated with impairment included age, ethnicity, premorbid cognitive
performance, depression, stroke location, and history of previous stroke.
Associations with APOE*E4 (apolipoprotein E with the E4 allele) allele status and
sex were mixed. CONCLUSIONS: Stroke is associated with an increased risk of
cognitive decline, but cognitive decline is not a consequence. Factors associated
with decline, such as sociodemographic status, health-related comorbidity, stroke
history, and clinical features could be used in models to predict future risk of
dementia after stroke. A risk model approach could identify patients at greatest
risk for timely intervention to reduce the frequency or delay the onset of
poststroke cognitive impairment and dementia.
PMID- 29335320
TI - January 15th Question.
PMID- 29335319
TI - Preterm Delivery and Future Risk of Maternal Cardiovascular Disease: A Systematic
Review and Meta-Analysis.
AB - BACKGROUND: Preterm delivery (<37 weeks gestational age) affects 11% of all
pregnancies, but data are conflicting whether preterm birth is associated with
long-term adverse maternal cardiovascular outcomes. We aimed to systematically
evaluate and summarize the evidence on the relationship between preterm birth and
future maternal risk of cardiovascular diseases. METHODS AND RESULTS: A
systematic search of MEDLINE and EMBASE was performed to identify relevant
studies that evaluated the association between preterm birth and future maternal
risk of composite cardiovascular disease, coronary heart disease, stroke, and
death caused by cardiovascular or coronary heart disease and stroke. We
quantified the associations using random effects meta-analysis. Twenty-one
studies with over 5.8 million women, including over 338 000 women with previous
preterm deliveries, were identified. Meta-analysis of studies that adjusted for
potential confounders showed that preterm birth was associated with an increased
risk of maternal future cardiovascular disease (risk ratio [RR] 1.43, 95%
confidence interval [CI], 1.18, 1.72), cardiovascular disease death (RR 1.78, 95%
CI, 1.42, 2.21), coronary heart disease (RR 1.49, 95% CI, 1.38, 1.60), coronary
heart disease death (RR 2.10, 95% CI, 1.87, 2.36), and stroke (RR 1.65, 95% CI,
1.51, 1.79). Sensitivity analysis showed that the highest risks occurred when the
preterm deliveries occurred before 32 weeks gestation or were medically
indicated. CONCLUSIONS: Preterm delivery is associated with an increase in future
maternal adverse cardiovascular outcomes, including a 2-fold increase in deaths
caused by coronary heart disease. These findings support the assessment of
preterm delivery in cardiovascular risk assessment in women.
PMID- 29335321
TI - Effectiveness and Cost of Weekly Recombinant Tissue Plasminogen Activator
Hemodialysis Catheter Locking Solution.
AB - BACKGROUND AND OBJECTIVES: Evidence to guide hemodialysis catheter locking
solutions is limited. We aimed to assess effectiveness and cost of recombinant
tissue plasminogen activator (rt-PA) once per week as a locking solution,
compared with thrice weekly citrate or heparin, in patients at high risk of
complications. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used a
prospective design and pre-post comparison in three sites across Canada. Pre-post
comparisons were conducted using multilevel mixed effects regression models
accounting for cluster with site and potential enrollment of patients more than
once. In the pre period, catheter malfunction was managed as per site-specific
standard of care. The intervention in the post period was once weekly rt-PA as a
locking solution (with citrate or heparin used for other sessions). The primary
outcome was rate of rt-PA use for treatment of catheter malfunction. Secondary
outcomes included rates of bacteremia, management of catheter malfunction, and
cost. RESULTS: There were 374 patients (mean age 68 years; 52% men) corresponding
to 506 enrollments. Mean length of enrollment was 200 days (SD 119) in the pre
period and 187 days (SD 101) in the post period. There was a significant decline
in rate of rt-PA use for treatment of catheter malfunction in the post compared
with pre period (adjusted incidence rate ratio, 0.39; 95% confidence interval,
0.30 to 0.52); however, there was no difference in the rate of bacteremia, or
catheter stripping or removal/replacement. The increase in mean total health care
cost in the post period was CAD$962 per enrollment, largely related to costs of
rt-PA as a locking solution. CONCLUSIONS: Once weekly rt-PA as a catheter locking
solution was associated with a reduction in rt-PA use for treatment of catheter
malfunction. Our results showing a reduction in rescue rt-PA use are consistent
with a prior randomized trial, although we did not observe a reduction in
bacteremia or catheter stripping/removal and did observe an increased incremental
cost of this strategy primarily accounted for by the cost of the rt-PA.
PMID- 29335322
TI - Identifying patterns of communication in patients attending memory clinics: a
systematic review of observations and signs with potential diagnostic utility.
AB - BACKGROUND: Subjective cognitive complaints are commonly encountered in primary
care and often result in memory clinic referral. However, meta-analyses have
shown that such concerns do not consistently correspond to objective memory
impairment or predict future dementia. Memory clinic referrals are increasing,
with greater proportions of patients attending who do not have dementia. Studies
of interaction during memory clinic assessments have identified conversational
profiles that can differentiate between dementia and functional disorders of
memory. To date, studies exploring communication patterns for the purpose of
diagnosis have not been reviewed. Such profiles could reduce unnecessary
investigations in patients without dementia. AIM: To identify and collate signs
and observable features of communication, which could clinically differentiate
between dementia and functional disorders of memory. DESIGN AND SETTING: This was
a systematic review and synthesis of evidence from studies with heterogeneous
methodologies. METHOD: A qualitative, narrative description and typical memory
clinic assessment were employed as a framework. RESULTS: Sixteen studies met the
criteria for selection. Two overarching themes emerged: 1) observable clues to
incapacity and cognitive impairment during routine assessment and interaction,
and 2) strategies and accounts for loss of abilities in people with dementia.
CONCLUSION: Whether the patient attends with a companion, how they participate,
give autobiographical history, demonstrate working memory, and make qualitative
observations during routine cognitive testing are all useful in building a
diagnostic picture. Future studies should explore these phenomena in larger
populations, over longer periods, include dementia subtypes, and develop robust
definitions of functional memory disorders to facilitate comparison.
PMID- 29335323
TI - Antibiotic prescribing quality for children in primary care: an observational
study.
AB - BACKGROUND: Overuse and inappropriate prescribing of antibiotics is driving
antibiotic resistance. GPs often prescribe antibiotics for upper respiratory
tract infections (URTIs) in young children despite their marginal beneficial
effects. AIM: To assess the quality of antibiotic prescribing for common
infections in young children attending primary care and to investigate
influencing factors. DESIGN AND SETTING: An observational, descriptive analysis,
including children attending primary care sites in England and Wales. METHOD: The
Diagnosis of Urinary Tract infection in Young children study collected data on
7163 children aged <5 years, presenting to UK primary care with an acute illness
(<28 days). Data were compared with the European Surveillance of Antimicrobial
Consumption Network (ESAC-Net) disease-specific quality indicators to assess
prescribing for URTIs, tonsillitis, and otitis media, against ESAC-Net proposed
standards. Non-parametric trend tests and chi2 tests assessed trends and
differences in prescribing by level of deprivation, site type, and demographics.
RESULTS: Prescribing rates fell within the recommendations for URTIs but exceeded
the recommended limits for tonsillitis and otitis media. The proportion of
children receiving the recommended antibiotic was below standards for URTIs and
tonsillitis, but within the recommended limits for otitis media. Prescribing
rates increased as the level of deprivation decreased for all infections
(P<0.05), and increased as the age of the child increased for URTIs and
tonsillitis (P<0.05). There were no other significant trends or differences.
CONCLUSION: The quality of antibiotic prescribing in this study was mixed and
highlights the scope for future improvements. There is a need to assess further
the quality of disease-specific antibiotic prescribing in UK primary care
settings using data representative of routine clinical practice.
PMID- 29335324
TI - Prevalence of primary aldosteronism in primary care: a cross-sectional study.
AB - BACKGROUND: Primary aldosteronism (PA) is the most frequent cause of secondary
hypertension. Reported prevalences of PA vary considerably because of a large
heterogeneity in study methodology. AIM: To examine the proportion of patients
with PA among patients with newly diagnosed, never treated hypertension. DESIGN
AND SETTING: A cross-sectional study set in primary care. METHOD: GPs measured
aldosterone and renin in adult patients with newly diagnosed, never treated
hypertension. Patients with elevated aldosterone-to-renin ratio and increased
plasma aldosterone concentration underwent a saline infusion test to confirm or
exclude PA. The source population was meticulously assessed to detect possible
selection bias. RESULTS: Of 3748 patients with newly diagnosed hypertension, 343
patients were screened for PA. In nine out of 74 patients with an elevated
aldosterone-to-renin ratio and increased plasma aldosterone concentration the
diagnosis of PA was confirmed by a saline infusion test, resulting in a
prevalence of 2.6% (95% confidence interval = 1.4 to 4.9). All patients with PA
were normokalaemic and 8 out of 9 patients had sustained blood pressure >150/100
mmHg. Screened patients were younger (P<0.001) or showed higher blood pressure
(P<0.001) than non-screened patients. CONCLUSION: In this study a prevalence of
PA of 2.6% in a primary care setting was established, which is lower than
estimates reported from other primary care studies so far. This study supports
the screening strategy as recommended by the Endocrine Society Clinical Practice
Guideline. The low proportion of screened patients (9.2%), of the large cohort of
eligible patients, reflects the difficulty of conducting prevalence studies in
primary care clinical practice.
PMID- 29335325
TI - Population and patient factors affecting emergency department attendance in
London: retrospective cohort analysis of linked primary and secondary care
records.
AB - BACKGROUND: Population factors, including social deprivation and morbidity,
predict the use of emergency departments (EDs). AIM: To link patient-level
primary and secondary care data to determine whether the association between
deprivation and ED attendance is explained by multimorbidity and other clinical
factors in the GP record. DESIGN AND SETTING: Retrospective cohort study based in
East London. METHOD: Primary care demographic, consultation, diagnostic, and
clinical data were linked with ED attendance data. GP Patient Survey (GPPS)
access questions were linked to practices. RESULTS: Adjusted multilevel analysis
for adults showed a progressive rise in ED attendance with increasing numbers of
long-term conditions (LTCs). Comparing two LTCs with no conditions, the odds
ratio (OR) is 1.28 (95% confidence interval [CI] = 1.25 to 1.31); comparing four
or more conditions with no conditions, the OR is 2.55 (95% CI = 2.44 to 2.66).
Increasing annual GP consultations predicted ED attendance: comparing zero with
more than two consultations, the OR is 2.44 (95% CI = 2.40 to 2.48). Smoking (OR
1.30, 95% CI = 1.28 to 1.32), being housebound (OR 2.01, 95% CI = 1.86 to 2.18),
and age also predicted attendance. Patient-reported access scores from the GPPS
were not a significant predictor. For children, younger age, male sex, white
ethnicity, and higher GP consultation rates predicted attendance. CONCLUSION:
Using patient-level data rather than practice-level data, the authors demonstrate
that the burden of multimorbidity is the strongest clinical predictor of ED
attendance, which is independently associated with social deprivation. Low use of
the GP surgery is associated with low attendance at ED. Unlike other studies, the
authors found that adult patient experience of GP access, reported at practice
level, did not predict use.
PMID- 29335326
TI - Attendance of routine childcare visits in primary care for children of mothers
with depression: a nationwide population-based cohort study.
AB - BACKGROUND: Depression is a common and potentially debilitating illness
worldwide. Attendance to routine childcare appointments is a key point of
interest in the effort to improve the health and care for families facing
depression. AIM: To evaluate the association between maternal depression and
offspring non-attendance to the Danish childcare and vaccination programme (CCP)
for children from 0-5 years of age. The CCP consists of seven separate visits and
several vaccinations. To investigate if exposure to recent and previous
depression may affect attendance differently. DESIGN AND SETTING: Population
based cohort study using Danish nationwide registers. METHOD: Participants were
all live-born children (n = 853 315) in Denmark in the period from 1 January 2000
until 31 August 2013, and their mothers. The outcome of interest was non
attendance of each one of the seven scheduled childcare visits and two
vaccination entities in the CCP. Exposure was maternal (both previous and recent)
depression. All information was obtained from Danish national registries.
RESULTS: The risk of not attending CCP was higher for children of mothers with
depression. For children of mothers with previous depression, the relative risk
(RR) was 1.01 (95% confidence interval [CI] = 0.98 to 1.03) at the 5-week
childcare visit, and 1.12 (95% CI = 1.09 to 1.14) at the 5-year childcare visit.
For children of mothers with recent depression, the RR was 1.07 (95% CI = 1.03 to
1.13) at the 5-week visit, and 1.15 (95% CI = 1.13 to 1.17) at the 5-year visit.
Furthermore, the risk of missing at least four of the seven childcare visits was
higher for children of females with maternal depression (RR = 1.16, 95% CI = 1.13
to 1.19). CONCLUSION: Maternal depression seems to compromise CCP attendance.
These findings suggest a need for careful clinical attention to these vulnerable
families, even years after a diagnosis of depression.
PMID- 29335327
TI - GPs' experiences of diagnosing and managing childhood eczema: a qualitative study
in primary care.
AB - BACKGROUND: Eczema is common among children, and in the UK the majority are
managed by GPs. The most common cause of poor disease control is incorrect use of
topical treatments. There is a lack of research into the challenges faced by GPs
in diagnosing and managing this condition. AIM: To explore the experiences of GPs
in assessing and managing children with eczema. DESIGN AND SETTING: Qualitative
study in primary care in England. METHOD: Semi-structured interviews with 15 GPs
were audiorecorded, transcribed verbatim, and analysed thematically using the
framework method. RESULTS: GPs described a paucity of dermatology training.
Although most GPs were confident diagnosing uncomplicated eczema, they reported
using a trial-and-error approach to prescribing emollients, and were uncertain
about quantities of topical treatments to issue. Mild and moderate potency
topical corticosteroids (TCS) were commonly used, but most GPs lacked confidence
in recommending potent TCS, and viewed parents or carers to be fearful of using
all strengths of TCS. GPs perceived adherence to treatments to be low, but
provision of information to support self-care was variable. Routine review of
medication use or disease control was uncommon, which GPs attributed to service
constraints. Participants' views on the causes and management of eczema were
perceived to be at odds with parents and carers, who were said to be overly
focused on an underlying cause, such as allergy. CONCLUSION: GP uncertainty in
managing eczema, lack of routine information and review, and perceived dissonance
with parents around causation and management may be contributing to low
concordance with treatments.
PMID- 29335328
TI - Walking prescription of 10 000 steps per day in patients with type 2 diabetes
mellitus: a randomised trial in Nigerian general practice.
AB - BACKGROUND: In clinical practice, translating the benefits of a sustained
physically active lifestyle on glycaemic control in patients with type 2 diabetes
mellitus (T2DM) is difficult. A walking prescription may be an effective
alternative. AIM: To examine the effect of a 10 000 steps per day prescription on
glycaemic control of patients with T2DM. DESIGN AND SETTING: Forty-six adults
with T2DM attending a general outpatient clinic were randomised into two equal
groups. The intervention group was given goals to accumulate 10 000 steps per day
for 10 weeks, whereas the control group maintained their normal activity habits.
METHOD: Daily step count was measured with waist-mounted pedometer and baseline
and endline average steps per day. Glycosylated haemoglobin (HbA1c),
anthropometric, and cardiovascular measurements were also obtained. An intention
to-treat analysis was done. RESULTS: The average baseline step count was 4505
steps per day for all participants, and the average step count in the
intervention group for the last 4 weeks of the study period was higher by 2913
steps per day (95% confidence interval [CI] = 1274 to 4551, F (2, 37.7) = 18.90,
P<0.001). Only 6.1% of the intervention group participants achieved the 10 000
steps per day goal. The mean baseline HbA1c was 6.6% (range = 5.3 to 9.0).
Endline HbA1c was lower in the intervention group than in the control group (mean
difference -0.74%, 95% CI = -1.32 to -0.02, F = 12.92, P = 0.015) after adjusting
for baseline HbA1c. There was no change in anthropometric and cardiovascular
indices. CONCLUSION: Adherence to 10 000 steps per day prescription is low but
may still be associated with improved glycaemic control in T2DM. Motivational
strategies for better adherence would improve glycaemic control.
PMID- 29335329
TI - Relocating patients from a specialist homeless healthcare centre to general
practices: a multi-perspective study.
AB - BACKGROUND: The relocation of formerly homeless patients eligible to transfer
from a specialist homeless healthcare centre (SHHC) to mainstream general
practices is key to patient integration in the local community. Failure to
transition patients conferring eligibility for relocation may also negatively
impact on SHHC service delivery. AIM: To explore barriers and facilitators of
relocation from the perspectives of formerly homeless patients and healthcare
staff involved in their care. DESIGN AND SETTING: Qualitative semi-structured
face-to-face and telephone interviews conducted in the north east of Scotland.
METHOD: Participants were patients and healthcare staff including GPs, nurses,
substance misuse workers, administrative, and local community pharmacy staff
recruited from one SHHC, two mainstream general practices, and four community
pharmacies. Interview schedules based on the 14 domains of the Theoretical
Domains Framework (TDF) were drafted. Transcripts of the interviews were analysed
by two independent researchers using a framework approach. RESULTS: Seventeen
patients and 19 staff participated. Key barriers and facilitators aligned to TDF
domains included: beliefs about consequences regarding relocation; patient
intention to relocate; environmental context and resources in relation to the
care of the patients and assessing patient eligibility; patient skills in
relation to integration; social and professional role and identity of staff and
patients; and emotional attachment to the SHHC. CONCLUSION: Implementation of
services, which promote relocation and integration, may optimise patient
relocation from SHHCs to mainstream general practices. These include peer support
networks for patients, better information provision on the relocation process,
and supporting patients in the journey of identifying and adjusting to mainstream
practices.
PMID- 29335330
TI - Stroke Incidence and Outcomes in Northeastern Greece: The Evros Stroke Registry.
AB - BACKGROUND AND PURPOSE: Data are scarce on both stroke incidence rates and
outcomes in Greece and in rural areas in particular. We performed a prospective
population-based study evaluating the incidence of first-ever stroke in the Evros
prefecture, a region of a total 147 947 residents located in North Eastern
Greece. METHODS: Adult patients with first-ever stroke were registered during a
24-month period (2010-2012) and followed up for 12 months. To compare our stroke
incidence with that observed in other studies, we standardized our incidence rate
data according to the European Standard Population, World Health Organization,
and Segi population. We also applied criteria of data quality proposed by the
Monitoring Trends and Determinants in Cardiovascular Disease project. Stroke
diagnosis and classification were performed using World Health Organization
criteria on the basis of neuroimaging and autopsy data. RESULTS: We prospectively
documented 703 stroke cases (mean age: 75+/-12 years; 52.8% men; ischemic stroke:
80.8%; intracerebral hemorrhage: 11.8%; subarachnoid hemorrhage: 4.4%; undefined:
3.0%) with a total follow-up time of 119 805 person-years. The unadjusted and
European Standard Population-adjusted incidences of all strokes were 586.8 (95%
confidence interval [CI], 543.4-630.2) and 534.1 (95% CI, 494.6-573.6) per 100
000 person-years, respectively. The unadjusted incidence rates for ischemic
stroke, intracerebral hemorrhage, and subarachnoid hemorrhage were 474.1 (95% CI,
435-513), 69.3 (95% CI, 54-84), and 25.9 (95% CI, 17-35) per 100 000 person
years, respectively. The corresponding European Standard Population-adjusted
incidence rates per 100 000 person-years were 425.9 (95% CI, 390.9-460.9), 63.3
(95% CI, 49.7-76.9), and 25.8 (95% CI, 16.7-34.9) for ischemic stroke,
intracerebral hemorrhage, and subarachnoid hemorrhage, respectively. The overall
28-day case fatality rate was 21.3% (95% CI, 18.3%-24.4%) for all strokes and was
higher in hemorrhagic strokes than ischemic stroke (40.4%, 95% CI, 31.3%-49.4%
versus 16.2%, 95% CI, 13.2%-19.2%). CONCLUSIONS: This is the largest to date
population-based study in Greece documenting one of the highest stroke incidences
ever reported in South Europe, highlighting the need for efficient stroke
prevention and treatment strategies in Northeastern Greece.
PMID- 29335332
TI - Historical Slavery and Modern-Day Stroke Mortality in the United States Stroke
Belt.
PMID- 29335331
TI - Cerebrovascular Disease Knowledge Portal: An Open-Access Data Resource to
Accelerate Genomic Discoveries in Stroke.
PMID- 29335333
TI - Predictors of In-Hospital Death After Aneurysmal Subarachnoid Hemorrhage:
Analysis of a Nationwide Database (Swiss SOS [Swiss Study on Aneurysmal
Subarachnoid Hemorrhage]).
AB - BACKGROUND AND PURPOSE: To identify predictors of in-hospital mortality in
patients with aneurysmal subarachnoid hemorrhage and to estimate their impact.
METHODS: Retrospective analysis of prospective data from a nationwide multicenter
registry on all aneurysmal subarachnoid hemorrhage cases admitted to a tertiary
neurosurgical department in Switzerland (Swiss SOS [Swiss Study on Aneurysmal
Subarachnoid Hemorrhage]; 2009-2015). Both clinical and radiological independent
predictors of in-hospital mortality were identified, and their effect size was
determined by calculating adjusted odds ratios (aORs) using multivariate logistic
regression. Survival was displayed using Kaplan-Meier curves. RESULTS: Data of
n=1866 aneurysmal subarachnoid hemorrhage patients in the Swiss SOS database were
available. In-hospital mortality was 20% (n=373). In n=197 patients (10.6%),
active treatment was discontinued after hospital admission (no aneurysm occlusion
attempted), and this cohort was excluded from analysis of the main statistical
model. In the remaining n=1669 patients, the rate of in-hospital mortality was
13.9% (n=232). Strong independent predictors of in-hospital mortality were
rebleeding (aOR, 7.69; 95% confidence interval, 3.00-19.71; P<0.001), cerebral
infarction attributable to delayed cerebral ischemia (aOR, 3.66; 95% confidence
interval, 1.94-6.89; P<0.001), intraventricular hemorrhage (aOR, 2.65; 95%
confidence interval, 1.38-5.09; P=0.003), and new infarction post-treatment (aOR,
2.57; 95% confidence interval, 1.43-4.62; P=0.002). CONCLUSIONS: Several-and
among them modifiable-factors seem to be associated with in-hospital mortality
after aneurysmal subarachnoid hemorrhage. Our data suggest that strategies aiming
to reduce the risk of rebleeding are most promising in patients where active
treatment is initially pursued. CLINICAL TRIAL REGISTRATION: URL:
http://www.clinicaltrials.gov. Unique identifier: NCT03245866.
PMID- 29335334
TI - Diagnosis of Cerebral Amyloid Angiopathy: Evolution of the Boston Criteria.
PMID- 29335335
TI - Closure of Patent Foramen Ovale Versus Medical Therapy in Patients With
Cryptogenic Stroke or Transient Ischemic Attack: Updated Systematic Review and
Meta-Analysis.
AB - BACKGROUND AND PURPOSE: Previous systematic reviews and meta-analyses compared
the efficacy and safety of patent foramen ovale (PFO) closure versus medical
treatment in patients with cryptogenic stroke or transient ischemic attack (TIA).
Recently, new evidence from randomized trials became available. METHODS: We
searched PubMed until September 24, 2017, for trials comparing PFO closure with
medical treatment in patients with cryptogenic stroke/TIA using the items: stroke
or cerebrovascular accident or TIA and patent foramen ovale or paradoxical
embolism and trial or study. RESULTS: Among 851 identified articles, 5 were
eligible. In 3627 patients with 3.7-year mean follow-up, there was significant
difference in ischemic stroke recurrence (0.53 versus 1.1 per 100 patient-years,
respectively; odds ratio [OR], 0.43; 95% confidence intervals (CI), 0.21-0.90;
relative risk reduction, 50.5%; absolute risk reduction, 2.11%; and number needed
to treat to prevent 1 event, 46.5 for 3.7 years). There was no significant
difference in TIAs (0.78 versus 0.98 per 100 patient-years, respectively; OR,
0.80; 95% CI, 0.53-1.19) and all-cause mortality (0.18 versus 0.23 per 100
patient-years, respectively; OR, 0.73; 95% CI, 0.34-1.56). New-onset atrial
fibrillation occurred more frequently in the PFO closure arm (1.3 versus 0.25 per
100 patient-years, respectively; OR, 5.15; 95% CI, 2.18-12.15) and resolved in
72% of cases within 45 days, whereas rates of myocardial infarction (0.12 versus
0.09 per 100 patient-years, respectively; OR, 1.22; 95% CI, 0.25-5.91) and any
serious adverse events (7.3 versus 7.3 per 100 patient-years, respectively; OR,
1.07; 95% CI, 0.92-1.25) were similar. CONCLUSIONS: In patients with cryptogenic
stroke/TIA and PFO who have their PFO closed, ischemic stroke recurrence is less
frequent compared with patients receiving medical treatment. Atrial fibrillation
is more frequent but mostly transient. There is no difference in TIA, all-cause
mortality, or myocardial infarction.
PMID- 29335336
TI - Periodontal Disease, Regular Dental Care Use, and Incident Ischemic Stroke.
AB - BACKGROUND AND PURPOSE: Periodontal disease is independently associated with
cardiovascular disease. Identification of periodontal disease as a risk factor
for incident ischemic stroke raises the possibility that regular dental care
utilization may reduce the stroke risk. METHODS: In the ARIC (Atherosclerosis
Risk in Communities) study, pattern of dental visits were classified as regular
or episodic dental care users. In the ancillary dental ARIC study, selected
subjects from ARIC underwent fullmouth periodontal measurements collected at 6
sites per tooth and classified into 7 periodontal profile classes (PPCs).
RESULTS: In the ARIC study 10 362 stroke-free participants, 584 participants had
incident ischemic strokes over a 15-year period. In the dental ARIC study, 6736
dentate subjects were assessed for periodontal disease status using PPC with a
total of 299 incident ischemic strokes over the 15-year period. The 7 levels of
PPC showed a trend toward an increased stroke risk (chi2 trend P<0.0001); the
incidence rate for ischemic stroke/1000-person years was 1.29 for PPC-A (health),
2.82 for PPC-B, 4.80 for PPC-C, 3.81 for PPC-D, 3.50 for PPC-E, 4.78 for PPC-F,
and 5.03 for PPC-G (severe periodontal disease). Periodontal disease was
significantly associated with cardioembolic (hazard ratio, 2.6; 95% confidence
interval, 1.2-5.6) and thrombotic (hazard ratio, 2.2; 95% confidence interval,
1.3-3.8) stroke subtypes. Regular dental care utilization was associated with
lower adjusted stroke risk (hazard ratio, 0.77; 95% confidence interval, 0.63
0.94). CONCLUSIONS: We confirm an independent association between periodontal
disease and incident stroke risk, particularly cardioembolic and thrombotic
stroke subtype. Further, we report that regular dental care utilization may lower
this risk for stroke.
PMID- 29335337
TI - Salivary glands regenerate after radiation injury through SOX2-mediated secretory
cell replacement.
AB - Salivary gland acinar cells are routinely destroyed during radiation treatment
for head and neck cancer that results in a lifetime of hyposalivation and co
morbidities. A potential regenerative strategy for replacing injured tissue is
the reactivation of endogenous stem cells by targeted therapeutics. However, the
identity of these cells, whether they are capable of regenerating the tissue, and
the mechanisms by which they are regulated are unknown. Using in vivo and ex vivo
models, in combination with genetic lineage tracing and human tissue, we discover
a SOX2+ stem cell population essential to acinar cell maintenance that is capable
of replenishing acini after radiation. Furthermore, we show that acinar cell
replacement is nerve dependent and that addition of a muscarinic mimetic is
sufficient to drive regeneration. Moreover, we show that SOX2 is diminished in
irradiated human salivary gland, along with parasympathetic nerves, suggesting
that tissue degeneration is due to loss of progenitors and their regulators.
Thus, we establish a new paradigm that salivary glands can regenerate after
genotoxic shock and do so through a SOX2 nerve-dependent mechanism.
PMID- 29335340
TI - Anticitrullinated Protein Antibodies Induce Inflammatory Gene Expression Profile
in Peripheral Blood Cells from CCP-positive Patients with RA.
AB - OBJECTIVE: Anticitrullinated protein antibodies (ACPA) have major diagnostic
significance in rheumatoid arthritis (RA). ACPA are directed against different
citrullinated antigens, including filaggrin, fibrinogen, vimentin, and collagen.
The presence of ACPA is associated with joint damage and extraarticular
manifestations, suggesting that ACPA may have a significant role in the
pathogenesis of RA. METHODS: To verify the effect of ACPA on RA-immune cells,
peripheral blood mononuclear cells (PBMC) from cyclic citrullinated peptide (CCP)
positive patients with RA and healthy controls were cocultured in vitro with
ACPA. ACPA-positive stained cells were analyzed by flow cytometry and the effect
of ACPA on mRNA expression levels was evaluated by real-time PCR. We tested
whether the stimulatory effects induced by ACPA could be inhibited by the
addition of a new multiepitope citrullinated peptide (Cit-ME). RESULTS: We found
that ACPA bind specifically to PBMC from CCP-positive patients with RA through
the Fab portion. ACPA induce upregulation of pathogenic cytokine expression (4-
to 13-fold increase) in PBMC derived from CCP-positive patients with RA.
Moreover, ACPA upregulated IL-1beta and IL-6 mRNA expression levels by 10- and 6
fold, respectively, compared to control IgG. Cit-ME, a genuine ligand of ACPA,
inhibited the ACPA-induced upregulation of IL-1beta and IL-6 by 30%. CONCLUSION:
ACPA bind to a limited percentage of PBMC and upregulate inflammatory cytokine
expression, suggesting that ACPA is involved in RA pathogenesis. Targeting ACPA
to decrease their pathogenic effects might provide a novel direction in
developing therapeutic strategies for RA.
PMID- 29335341
TI - Trends in Healthcare Expenditures among Individuals with Arthritis in the United
States from 2008 to 2014.
AB - OBJECTIVE: With the expected rise in the arthritis population, information is
required regarding trends of healthcare expenditures among individuals with
arthritis in the United States. We examined temporal trends in direct and out-of
pocket (OOP) healthcare expenditures among individuals with arthritis using a
nationally representative database, the Medical Expenditures Panel Survey.
METHODS: The study population was composed of cross-sectional cohorts of
individuals aged >= 18 years from 2008 to 2014. Two-part models were used to
estimate the incremental total and types of annual direct and OOP healthcare
expenditures (adjusted to 2014 US dollars) for arthritis, after controlling for
predisposing, enabling, need, personal health practice, and external
environmental factors, as per the Anderson Healthcare Behavioral Model. RESULTS:
An annual weighted arthritis population rose from 56.1 million in 2008 to 65.1
million in 2014. Among individuals with arthritis, the annual average direct and
OOP expenditure was $10,424 [standard error (SE) = $345, aggregate = $584.8
billion] and $1493 (SE = $50, aggregate = $83.8 billion) in 2008, respectively,
and $910 (SE = $279, total = $645.1 billion) and $1099 (SE = $36, aggregate =
$71.5 billion) in 2014, respectively. In the fully adjusted model, individuals
with arthritis had significantly greater total and OOP expenditures from 2008 to
2014; however, the magnitude of incremental OOP expenditure declined from 2008 to
2014. CONCLUSION: Although the annual direct healthcare expenditures per person
remained stable over the years, the rise in proportion of the arthritis
population led to a huge increase in aggregate economic burden to the US
healthcare system.
PMID- 29335338
TI - CRTH2 promotes endoplasmic reticulum stress-induced cardiomyocyte apoptosis
through m-calpain.
AB - Apoptotic death of cardiac myocytes is associated with ischemic heart disease and
chemotherapy-induced cardiomyopathy. Chemoattractant receptor-homologous molecule
expressed on T helper type 2 cells (CRTH2) is highly expressed in the heart.
However, its specific role in ischemic cardiomyopathy is not fully understood.
Here, we demonstrated that CRTH2 disruption markedly improved cardiac recovery in
mice postmyocardial infarction and doxorubicin challenge by suppressing
cardiomyocyte apoptosis. Mechanistically, CRTH2 activation specifically
facilitated endoplasmic reticulum (ER) stress-induced cardiomyocyte apoptosis via
caspase-12-dependent pathway. Blockage of m-calpain prevented CRTH2-mediated
cardiomyocyte apoptosis under ER stress by suppressing caspase-12 activity. CRTH2
was coupled with Galphaq to elicit intracellular Ca2+ flux and activated m
calpain/caspase-12 cascade in cardiomyocytes. Knockdown of caspase-4, an
alternative to caspase-12 in humans, markedly alleviated CRHT2 activation-induced
apoptosis in human cardiomyocyte response to anoxia. Our findings revealed an
unexpected role of CRTH2 in promoting ER stress-induced cardiomyocyte apoptosis,
suggesting that CRTH2 inhibition has therapeutic potential for ischemic
cardiomyopathy.
PMID- 29335339
TI - Inhibition of Drp1/Fis1 interaction slows progression of amyotrophic lateral
sclerosis.
AB - Bioenergetic failure and oxidative stress are common pathological hallmarks of
amyotrophic lateral sclerosis (ALS), but whether these could be targeted
effectively for novel therapeutic intervention needs to be determined. One of the
reported contributors to ALS pathology is mitochondrial dysfunction associated
with excessive mitochondrial fission and fragmentation, which is predominantly
mediated by Drp1 hyperactivation. Here, we determined whether inhibition of
excessive fission by inhibiting Drp1/Fis1 interaction affects disease
progression. We observed mitochondrial excessive fragmentation and dysfunction in
several familial forms of ALS patient-derived fibroblasts as well as in cultured
motor neurons expressing SOD1 mutant. In both cell models, inhibition of
Drp1/Fis1 interaction by a selective peptide inhibitor, P110, led to a
significant reduction in reactive oxygen species levels, and to improvement in
mitochondrial structure and functions. Sustained treatment of mice expressing
G93A SOD1 mutation with P110, beginning at the onset of disease symptoms at day
90, produced an improvement in motor performance and survival, suggesting that
Drp1 hyperactivation may be an attractive target in the treatment of ALS
patients.
PMID- 29335342
TI - Comparative Efficacy of Tumor Necrosis Factor-alpha Inhibitors in Ankylosing
Spondylitis: A Systematic Review and Bayesian Network Metaanalysis.
AB - OBJECTIVE: To compare the efficacy of 6 tumor necrosis factor-alpha inhibitors
(TNFi) in treatment of ankylosing spondylitis (AS) at 12 weeks and 24 weeks.
METHODS: We performed a systematic literature review of randomized controlled
trials of TNFi in patients with active AS. We included trials that reported
efficacy at 10 to 14 weeks (12-week analysis) and at 24 to 30 weeks (24-week
analysis). We used Bayesian network metaanalysis (NMA) to compare their relative
efficacy to improve the Bath Ankylosing Spondylitis Disease Activity Index
(BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and C-reactive
protein (CRP) level. RESULTS: We included 20 trials of 6 TNFi, with 43 treatment
arms and 3220 participants. All TNFi were significantly better than placebo in
reducing BASDAI and BASFI at 12 weeks and 24 weeks; all but certolizumab pegol
(CZP) were statistically better than placebo in reducing CRP at 12 weeks; all but
CZP and infliximab-dyyb (IFX biosimilar) were significantly better than placebo
in reducing CRP at 24 weeks. IFX was superior to the other TNFi in decreasing
BASDAI at 12 weeks, but not at 24 weeks. Excluding 1 open-label trial, there were
no differences among TNFi. CONCLUSION: Based on this NMA of clinical trials, IFX
was superior to other TNFi in reducing BASDAI at 12 weeks, but sensitive to
inclusion of an open-label trial, and its efficacy was diminished at 24 weeks.
The analysis was limited by few direct comparison trials. Further study of
relative safety and longterm effectiveness will help inform the choice of TNFi in
treating active AS.
PMID- 29335343
TI - Association Between Glucocorticoid Exposure and Healthcare Expenditures for
Potential Glucocorticoid-related Adverse Events in Patients with Rheumatoid
Arthritis.
AB - OBJECTIVE: Oral glucocorticoid (OGC) use for rheumatoid arthritis (RA) is debated
because of the adverse event (AE) profile of OGC. We evaluated the associations
between cumulative doses of OGC and potential OGC-related AE, and quantified the
associated healthcare expenditures. METHODS: Using the MarketScan databases,
patients >= 18 years old who have RA with continuous enrollment from January 1 to
December 31, 2012 (baseline), and from January 1 to December 31, 2013 (evaluation
period), were identified. Cumulative OGC dose was measured using prescription
claims during the baseline period. Potential OGC-related AE (osteoporosis,
fracture, aseptic necrosis of the bone, type 2 diabetes, ulcer/gastrointestinal
bleeding, cataract, hospitalization for opportunistic infection, myocardial
infarction, or stroke) and AE-related expenditures (2013 US$) were gathered
during the evaluation period. Multivariable regression models were fitted to
estimate OR of AE and incremental costs for patients with AE. RESULTS: There were
84,357 patients analyzed, of whom 48% used OGC during the baseline period and 26%
had an AE during the evaluation period. A cumulative OGC dose > 1800 mg was
associated with an increased risk of any AE compared with no OGC exposure (OR
1.19, 99.65% CI 1.09-1.30). Incremental costs per patient with any AE were
significantly greater for cumulative OGC dose > 1800 mg compared with no OGC
exposure (incremental cost = $3528, 99.65% CI $2402-$4793). CONCLUSION: Chronic
exposure to low to medium doses of OGC was associated with significantly
increased risk of potential OGC-related AE in patients with RA, and greater
cumulative OGC dose was associated with substantially higher AE-related
healthcare expenditures among patients with AE.
PMID- 29335344
TI - Can Ultrasound Be Used to Predict Loss of Remission in Patients with RA in a Real
life Setting? A Multicenter Cohort Study.
AB - OBJECTIVE: Several studies have suggested that patients with rheumatoid arthritis
(RA) presenting with ultrasound (US) synovitis despite clinical remission have
more subsequent flares than those who show both clinical and sonographic
remission. The objective of our study was to investigate whether these results
could be translated to a real-life setting. METHODS: We compared the time from
the first US performed in clinical remission to loss of remission (defined by a
DAS28 > 2.6 or the need for stepping up treatment with disease-modifying
antirheumatic drugs) within the Swiss Clinical Quality Management cohort of
patients with RA, and we adjusted for relevant confounders. Analyses were
repeated for different definitions of US-detected synovitis (US+) using
greyscale, Doppler, and combined modes based on previously validated scores, and
they were adjusted for relevant confounders. RESULTS: There were 318 RA patients
with 378 remission phases included. Loss of clinical remission was observed in
60% of remission phases. Residual US synovitis was associated with a shorter
duration of clinical remission (median 2-5 mos) and a moderately increased hazard
ratio (HR) for loss of remission (HR 1.2-1.5), with the highest HR for the
combined US score. The association between US+ and loss of remission was
strongest when the US measurement had taken place early in remission (shorter
median duration of 6-20 mos) and when followup time was limited to the first 3 or
6 months (most HR between 2-4). CONCLUSION: US-detected synovitis, particularly
when US is performed early in clinical remission, has a moderate predictive power
for loss of remission in a real-life setting.
PMID- 29335346
TI - Severity of Sacroiliitis and Erythrocyte Sedimentation Rate are Associated with a
Low Trabecular Bone Score in Young Male Patients with Ankylosing Spondylitis.
AB - OBJECTIVE: To examine factors related to a low trabecular bone score (TBS) and
the association between TBS and vertebral fractures in patients with ankylosing
spondylitis (AS). METHODS: One hundred patients (all male, aged < 50 yrs) who
fulfilled the modified New York criteria for the classification of AS were
enrolled. The TBS and bone mineral density (BMD) were assessed using dual-energy
X-ray absorptiometry. Clinical variables, inflammatory markers, and the presence
of vertebral fractures were also assessed. Sacroiliitis grade and spinal
structural damage were measured using the modified New York criteria and the
Stoke Ankylosing Spondylitis Spine Score (SASSS). RESULTS: The mean TBS was 1.38
+/- 0.13. The TBS showed a positive correlation with BMD at the lumbar spine,
femoral neck, and total hip. TBS negatively correlated with SASSS, whereas BMD at
the lumbar spine showed a positive correlation. A significant decrease in TBS
values was observed in patients with spinal structural damage (p = 0.001).
Univariate analysis identified disease duration, erythrocyte sedimentation rate
(ESR), sacroiliitis grade, and SASSS as being associated with TBS. Multivariate
analysis identified ESR and sacroiliitis grade as being independently associated
with TBS (p = 0.006 and p < 0.001, respectively). Ten patients had morphometric
vertebral fractures. The mean TBS was lower in patients with vertebral fractures
than in age-matched patients without fractures (p = 0.028). Lower TBS predicted
vertebral fractures (area under curve = 0.733, cutoff = 1.311). CONCLUSION: The
TBS in young male patients with AS is associated with the ESR and severity of
sacroiliitis. The TBS may be useful as a tool for assessing osteoporosis in AS.
PMID- 29335345
TI - S100A12 Is Associated with Response to Therapy in Juvenile Idiopathic Arthritis.
AB - OBJECTIVE: Around one-third of patients with juvenile idiopathic arthritis (JIA)
fail to respond to first-line methotrexate (MTX) or anti-tumor necrosis factor
(TNF) therapy, with even fewer achieving >= American College of Rheumatology
Pediatric 70% criteria for response (ACRpedi70), though individual responses
cannot yet be accurately predicted. Because change in serum S100-protein myeloid
related protein complex 8/14 (MRP8/14) is associated with therapeutic response,
we tested granulocyte-specific S100-protein S100A12 as a potential biomarker for
treatment response. METHODS: S100A12 serum concentration was determined by ELISA
in patients treated with MTX (n = 75) and anti-TNF (n = 88) at baseline and
followup. Treatment response (>= ACRpedi50 score), achievement of inactive
disease, and improvement in Juvenile Arthritis Disease Activity Score (JADAS)-10
score were recorded. RESULTS: Baseline S100A12 concentration was measured in
patients treated with anti-TNF [etanercept n = 81, adalimumab n = 7; median 200,
interquartile range (IQR) 133-440 ng/ml] and MTX (median 220, IQR 100-440 ng/ml).
Of the patients in the anti-TNF therapy group, 74 (84%) were also receiving MTX.
Responders to MTX (n = 57/75) and anti-TNF (n = 66/88) therapy had higher
baseline S100A12 concentration compared to nonresponders: median 240 (IQR 125
615) ng/ml versus 150 (IQR 87-233) ng/ml, p = 0.021 for MTX, and median 308 (IQR
150-624) ng/ml versus 151 (IQR 83-201) ng/ml, p = 0.002, for anti-TNF therapy.
Followup S100A12 could be measured in 44/75 MTX-treated patients (34/44
responders) and 39/88 anti-TNF-treated patients (26/39 responders). Responders
had significantly reduced S100A12 concentration (MTX: p = 0.031, anti-TNF: p <
0.001) at followup versus baseline. Baseline serum S100A12 in both univariate and
multivariate regression models for anti-TNF therapy and univariate analysis alone
for MTX therapy was significantly associated with change in JADAS-10. CONCLUSION:
Responders to MTX or anti-TNF treatment can be identified by higher pretreatment
S100A12 serum concentration levels.
PMID- 29335348
TI - The Dorsal 4-finger Technique: A Novel Method to Examine Metacarpophalangeal
Joints in Patients with Rheumatoid Arthritis.
AB - OBJECTIVE: To describe the dorsal 4-finger technique (DFFT) in examining
metacarpophalangeal (MCP) joints of patients with rheumatoid arthritis (RA) and
compare it to the traditional 2-finger technique (TFT) using ultrasound (US) as a
gold standard. METHODS: Four rheumatologists evaluated 180 MCP joints of 18
patients with RA. All patients underwent US for greyscale (GSUS) and power
Doppler US (PDUS). Agreements between rheumatologists, the 2 techniques, and US
were evaluated using Cohen kappa and the first-order agreement coefficient (AC1)
kappa methods. RESULTS: The population comprised 17 females (94.4%) with a mean
(SD) age and disease duration of 56.8 (14.4) and 21.8 (12.9) years, respectively.
Eight patients (44.4%) were taking methotrexate monotherapy, while 10 patients
(55.6%) were receiving biologics. US evaluation revealed 69 (38.3%) and 30
(16.7%) joints exhibited synovitis grade 2-3 by GSUS and PDUS, respectively.
Effusion was documented in 30 joints (16.7%). The mean intraobserver agreement
using the DFFT and TFT were 80.5% and 86%, respectively. The mean interobserver
agreements using the DFFT and TFT were 84% and 74%, respectively. kappa agreement
with US findings was similar for both techniques in tender joints but was higher
for the DFFT in nontender joints (0.33 vs 0.07, p = 0.015 for GSUS) and (0.48 vs
0.11, p = 0.002 for PDUS). The DFFT had a higher sensitivity in detecting
ballottement by GSUS (0.47 vs 0.2, p < 0.001) and PDUS (0.60 vs 0.27, p < 0.001).
CONCLUSION: The DFFT is a novel, reproducible, and reliable method to examine MCP
joints, and it has a better correlation with US than the traditional TFT.
PMID- 29335347
TI - Smoking Is the Most Significant Modifiable Lung Cancer Risk Factor in Systemic
Lupus Erythematosus.
AB - OBJECTIVE: To assess lung cancer risk in systemic lupus erythematosus (SLE),
relative to demographics, drug exposures, smoking, and disease activity. METHODS:
We analyzed data from 14 SLE cohorts. We calculated adjusted HR estimates for
lung cancer in SLE, relative to demographics, smoking, time-dependent medication
exposures, and cumulative disease activity [mean adjusted SLE Disease Activity
Index (SLEDAI) scores]. This project was approved by the ethics boards of all
participating institutions, including the Institutional Review Board of the
McGill University Health Centre. The ethics approval number for the Cancer Risk
study is GEN-06-031. RESULTS: Within these 14 SLE cohorts, 49 incident lung
cancers occurred. Among lung cancer cases, 59.0% were in the highest SLEDAI
quartile at baseline versus 40.8% of lung cancer-free SLE controls. The vast
majority (84.2%) of SLE lung cancer cases were ever-smokers at baseline, versus
40.1% of those without lung cancer. In adjusted models, the principal factors
associated with lung cancer were ever smoking (at cohort entry) and current age.
Estimated adjusted effects of all drugs were relatively imprecise, but did not
point toward any drug exposures as strong lung cancer risk factors. CONCLUSION:
We saw no clear evidence for drugs as a trigger for lung cancer risk in SLE,
although drug risk estimates were relatively imprecise. Smoking may be the most
significant modifiable lung cancer risk factor in SLE.
PMID- 29335349
TI - Efficacy of Continuous Interleukin 1 Blockade in Mevalonate Kinase Deficiency: A
Multicenter Retrospective Study in 13 Adult Patients and Literature Review.
AB - OBJECTIVE: To report efficacy and tolerance of interleukin 1 blockade in adult
patients with mevalonate kinase deficiency (MKD). METHODS: We retrospectively
collected data on 13 patients with MKD who had received anakinra (n = 10) and
canakinumab (n = 7). RESULTS: Anakinra resulted in complete or partial remission
in 3/10 and 5/10 patients, respectively, and no efficacy in 2/10, but a switch to
canakinumab led to partial remission. Canakinumab resulted in complete or partial
remission in 3/7 and 4/7 patients, respectively. CONCLUSION: These data support
frequent partial responses, showing a better response with canakinumab. The
genotype and therapeutic outcomes correlation should help in the personalization
of treatment.
PMID- 29335351
TI - Endocrinologist charged with murder of wife who threatened to reveal his opioid
dealing.
PMID- 29335350
TI - Epidemiology and Medication Pattern Change of Psoriatic Diseases in Taiwan from
2000 to 2013: A Nationwide, Population-based Cohort Study.
AB - OBJECTIVE: To analyze the trend of prevalence and incidence rates for psoriatic
arthritis (PsA) and psoriasis in Taiwan, and to determine the changes in
medication patterns. METHODS: Data were collected from the Taiwan National Health
Insurance Research Database, which covered at least 95% of the population from
2000 to 2013. International Classification of Diseases, 9th edition (ICD-9) was
used to identify PsA (ICD-9 696.0) and other psoriasis (ICD-9 696.1). Medications
were identified by Anatomical Therapeutic Chemical Classification code. We
calculated the annual age standardized prevalence and incidence rate of PsA and
psoriasis in individuals aged >= 16 years from 2000 to 2013, and used the Poisson
regression to test the trends by Wald chi-square statistic. RESULTS: The
prevalence (per 100,000 population) of psoriatic diseases between 2000 and 2013
increased from 11.12 to 37.75 for PsA, and from 179.2 to 281.5 for psoriasis. The
incidence (per 100,000 person-yrs) increased from 3.64 to 6.91 in PsA, while
there was no significant change in psoriasis. Prevalence and incidence in PsA
were more rapidly increased than in psoriasis. Sex ratio (men to women) of PsA
decreased from 2.0 to 1.5 in 2000 and 2013, respectively. There was an increase
in the use of disease-modifying antirheumatic drugs (DMARD), especially
biologics, which is significantly different from topical therapies. CONCLUSION:
The prevalence and incidence rates of psoriatic disease, especially PsA, were
increasing in Taiwan. The medication pattern showed an increase in DMARD and
biologics, while use of topical therapies decreased.
PMID- 29335352
TI - Discrete Modules and Mesoscale Functional Circuits for Thermal Nociception within
Primate S1 Cortex.
AB - This study addresses one long-standing question of whether functional separations
are preserved for somatosensory modalities of touch, heat, and cold nociception
within primate primary somatosensory (S1) cortex. This information is critical
for understanding how the nature of pain is represented in the primate brain.
Using a combination of submillimeter-resolution fMRI and microelectrode local
field potential (LFP) and spike recordings, we identified spatially segregated
cortical zones for processing touch and nociceptive heat and cold stimuli in
somatotopically appropriate areas 3a, 3b, 1, and 2 of S1 in male monkeys. The
distances between zones were comparable (~3.4 mm) across stimulus modalities
(heat, cold, and tactile), indicating the existence of uniform, modality-specific
modules. Stimulus-evoked LFP maps validated the fMRI maps in areas 3b and 1.
Isolation of heat and cold nociceptive neurons from the fMRI zones confirmed the
validity of using fMRI to probe nociceptive regions and circuits. Resting-state
fMRI analysis revealed distinct intrinsic functional circuits among functionally
related zones. We discovered distinct modular structures and networks for thermal
nociception within S1 cortex, a finding that has significant implications for
studying chronic pain syndromes and guiding the selection of neuromodulation
targets for chronic pain management.SIGNIFICANCE STATEMENT Primate S1 subregions
contain discrete heat and cold nociceptive modules. Modules with the same
properties exhibit strong functional connection. Nociceptive fMRI response
coincides with LFP and spike activities of nociceptive neurons. Functional
separation of heat and cold pain is retained within primate S1 cortex.
PMID- 29335353
TI - KChIP3 N-Terminal 31-50 Fragment Mediates Its Association with TRPV1 and
Alleviates Inflammatory Hyperalgesia in Rats.
AB - Potassium voltage-gated channel interacting protein 3 (KChIP3), also termed
downstream regulatory element antagonist modulator (DREAM) and calsenilin, is a
multifunctional protein belonging to the neuronal calcium sensor (NCS) family.
Recent studies revealed the expression of KChIP3 in dorsal root ganglion (DRG)
neurons, suggesting the potential role of KChIP3 in peripheral sensory
processing. Herein, we show that KChIP3 colocalizes with transient receptor
potential ion channel V1 (TRPV1), a critical molecule involved in peripheral
sensitization during inflammatory pain. Furthermore, the N-terminal 31-50
fragment of KChIP3 is capable of binding both the intracellular N and C termini
of TRPV1, which substantially decreases the surface localization of TRPV1 and the
subsequent Ca2+ influx through the channel. Importantly, intrathecal
administration of the transmembrane peptide transactivator of transcription (TAT)
31-50 remarkably reduces Ca2+ influx via TRPV1 in DRG neurons and alleviates
thermal hyperalgesia and gait alterations in a complete Freund's adjuvant-induced
inflammatory pain model in male rats. Moreover, intraplantar injection of TAT-31
50 attenuated the capsaicin-evoked spontaneous pain behavior and thermal
hyperalgesia, which further strengthened the regulatory role of TAT-31-50 on
TRPV1 channel. In addition, TAT-31-50 could also alleviate inflammatory thermal
hyperalgesia in kcnip3-/- rats generated in our study, suggesting that the
analgesic effect mediated by TAT-31-50 is independent of endogenous KChIP3. Our
study reveals a novel peripheral mechanism for the analgesic function of KChIP3
and provides a potential analgesic agent, TAT-31-50, for the treatment of
inflammatory pain.SIGNIFICANCE STATEMENT Inflammatory pain arising from inflamed
or injured tissues significantly compromises the quality of life in patients.
This study aims to elucidate the role of peripheral potassium channel interacting
protein 3 (KChIP3) in inflammatory pain. Direct interaction of the KChIP3 N
terminal 31-50 fragment with transient receptor potential ion channel V1 (TRPV1)
was demonstrated. The KChIP3-TRPV1 interaction reduces the surface localization
of TRPV1 and thus alleviates heat hyperalgesia and gait alterations induced by
peripheral inflammation. Furthermore, the transmembrane transactivator of
transcription (TAT)-31-50 peptide showed analgesic effects on inflammatory
hyperalgesia independently of endogenous KChIP3. This work reveals a novel
mechanism of peripheral KChIP3 in inflammatory hyperalgesia that is distinct from
its classical role as a transcriptional repressor in pain modulation.
PMID- 29335354
TI - Correction: Heat strain, volume depletion and kidney function in California
agricultural workers.
PMID- 29335355
TI - Snap, crackle and pop: when sneezing leads to crackling in the neck.
AB - Spontaneous perforation of the pharynx is an unusual condition. Due to its non
specific presentation and general lack of awareness, diagnosis and intervention
may be delayed resulting in potential complications. This case reports a rare
spontaneous perforation of the pyriform sinus after a forceful sneeze, leading to
cervical subcutaneous emphysema and pneumomediastinum.
PMID- 29335356
TI - Single Bursts of Individual Granule Cells Functionally Rearrange Feedforward
Inhibition.
AB - The sparse single-spike activity of dentate gyrus granule cells (DG GCs) is
punctuated by occasional brief bursts of 3-7 action potentials. It is well-known
that such presynaptic bursts in individual mossy fibers (MFs; axons of granule
cells) are often able to discharge postsynaptic CA3 pyramidal cells due to
powerful short-term facilitation. However, what happens in the CA3 network after
the passage of a brief MF burst, before the arrival of the next burst or solitary
spike, is not understood. Because MFs innervate significantly more CA3
interneurons than pyramidal cells, we focused on unitary MF responses in
identified interneurons in the seconds-long postburst period, using paired
recordings in rat hippocampal slices. Single bursts as short as 5 spikes in <30
ms in individual presynaptic MFs caused a sustained, large increase (tripling) in
the amplitude of the unitary MF-EPSCs for several seconds in ivy, axo
axonic/chandelier and basket interneurons. The postburst unitary MF-EPSCs in
these feedforward interneurons reached amplitudes that were even larger than the
MF-EPSCs during the bursts in the same cells. In contrast, no comparable
postburst enhancement of MF-EPSCs could be observed in pyramidal cells or
nonfeedforward interneurons. The robust postburst increase in MF-EPSCs in
feedforward interneurons was associated with significant shortening of the
unitary synaptic delay and large downstream increases in disynaptic IPSCs in
pyramidal cells. These results reveal a new cell type-specific plasticity that
enables even solitary brief bursts in single GCs to powerfully enhance inhibition
at the DG-CA3 interface in the seconds-long time-scales of interburst
intervals.SIGNIFICANCE STATEMENT The hippocampal formation is a brain region that
plays key roles in spatial navigation and learning and memory. The first stage of
information processing occurs in the dentate gyrus, where principal cells are
remarkably quiet, discharging low-frequency single action potentials interspersed
with occasional brief bursts of spikes. Such bursts, in particular, have
attracted a lot of attention because they appear to be critical for efficient
coding, storage, and recall of information. We show that single bursts of a few
spikes in individual granule cells result in seconds-long potentiation of
excitatory inputs to downstream interneurons. Thus, while it has been known that
bursts powerfully discharge ("detonate") hippocampal excitatory cells, this study
clarifies that they also regulate inhibition during the interburst intervals.
PMID- 29335357
TI - Nonlinear Relationship Between Spike-Dependent Calcium Influx and TRPC Channel
Activation Enables Robust Persistent Spiking in Neurons of the Anterior Cingulate
Cortex.
AB - Continuation of spiking after a stimulus ends (i.e. persistent spiking) is
thought to support working memory. Muscarinic receptor activation enables
persistent spiking among synaptically isolated pyramidal neurons in anterior
cingulate cortex (ACC), but a detailed characterization of that spiking is
lacking and the underlying mechanisms remain unclear. Here, we show that the rate
of persistent spiking in ACC neurons is insensitive to the intensity and number
of triggers, but can be modulated by injected current, and that persistent
spiking can resume after several seconds of hyperpolarization-imposed quiescence.
Using electrophysiology and calcium imaging in brain slices from male rats, we
determined that canonical transient receptor potential (TRPC) channels are
necessary for persistent spiking and that TRPC-activating calcium enters in a
spike-dependent manner via voltage-gated calcium channels. Constrained by these
biophysical details, we built a computational model that reproduced the observed
pattern of persistent spiking. Nonlinear dynamical analysis of that model
revealed that TRPC channels become fully activated by the small rise in
intracellular calcium caused by evoked spikes. Calcium continues to rise during
persistent spiking, but because TRPC channel activation saturates, firing rate
stabilizes. By calcium rising higher than required for maximal TRPC channel
activation, TRPC channels are able to remain active during periods of
hyperpolarization-imposed quiescence (until calcium drops below saturating
levels) such that persistent spiking can resume when hyperpolarization is
discontinued. Our results thus reveal that the robust intrinsic bistability
exhibited by ACC neurons emerges from the nonlinear positive feedback
relationship between spike-dependent calcium influx and TRPC channel
activation.SIGNIFICANCE STATEMENT Neurons use action potentials, or spikes, to
encode information. Some neurons can store information for short periods (seconds
to minutes) by continuing to spike after a stimulus ends, thus enabling working
memory. This so-called "persistent" spiking occurs in many brain areas and has
been linked to activation of canonical transient receptor potential (TRPC)
channels. However, TRPC activation alone is insufficient to explain many aspects
of persistent spiking such as resumption of spiking after periods of imposed
quiescence. Using experiments and simulations, we show that calcium influx caused
by spiking is necessary and sufficient to activate TRPC channels and that the
ensuing positive feedback interaction between intracellular calcium and TRPC
channel activation can account for many hitherto unexplained aspects of
persistent spiking.
PMID- 29335358
TI - Sox2 Is Essential for Oligodendroglial Proliferation and Differentiation during
Postnatal Brain Myelination and CNS Remyelination.
AB - In the CNS, myelination and remyelination depend on the successful progression
and maturation of oligodendroglial lineage cells, including proliferation and
differentiation of oligodendroglial progenitor cells (OPCs). Previous studies
have reported that Sox2 transiently regulates oligodendrocyte (OL)
differentiation in the embryonic and perinatal spinal cord and appears
dispensable for myelination in the postnatal spinal cord. However, the role of
Sox2 in OL development in the brain has yet to be defined. We now report that
Sox2 is an essential positive regulator of developmental myelination in the
postnatal murine brain of both sexes. Stage-specific paradigms of genetic
disruption demonstrated that Sox2 regulated brain myelination by coordinating
upstream OPC population supply and downstream OL differentiation. Transcriptomic
analyses further supported a crucial role of Sox2 in brain developmental
myelination. Consistently, oligodendroglial Sox2-deficient mice developed severe
tremors and ataxia, typical phenotypes indicative of hypomyelination, and
displayed severe impairment of motor function and prominent deficits of brain OL
differentiation and myelination persisting into the later CNS developmental
stages. We also found that Sox2 was required for efficient OPC proliferation and
expansion and OL regeneration during remyelination in the adult brain and spinal
cord. Together, our genetic evidence reveals an essential role of Sox2 in brain
myelination and CNS remyelination, and suggests that manipulation of Sox2 and/or
Sox2-mediated downstream pathways may be therapeutic in promoting CNS myelin
repair.SIGNIFICANCE STATEMENT Promoting myelin formation and repair has
translational significance in treating myelin-related neurological disorders,
such as periventricular leukomalacia and multiple sclerosis in which brain
developmental myelin formation and myelin repair are severely affected,
respectively. In this report, analyses of a series of genetic conditional knock
out systems targeting different oligodendrocyte stages reveal a previously
unappreciated role of Sox2 in coordinating upstream proliferation and downstream
differentiation of oligodendroglial lineage cells in the mouse brain during
developmental myelination and CNS remyelination. Our study points to the
potential of manipulating Sox2 and its downstream pathways to promote
oligodendrocyte regeneration and CNS myelin repair.
PMID- 29335359
TI - Recruitment of Additional Corticospinal Pathways in the Human Brain with State
Dependent Paired Associative Stimulation.
AB - Standard brain stimulation protocols modify human motor cortex excitability by
modulating the gain of the activated corticospinal pathways. However, the
restoration of motor function following lesions of the corticospinal tract
requires also the recruitment of additional neurons to increase the net
corticospinal output. For this purpose, we investigated a novel protocol based on
brain state-dependent paired associative stimulation.Motor imagery (MI)-related
electroencephalography was recorded in healthy males and females for brain state
dependent control of both cortical and peripheral stimulation in a brain-machine
interface environment. State-dependency was investigated with concurrent,
delayed, and independent stimulation relative to the MI task. Specifically,
sensorimotor event-related desynchronization (ERD) in the beta-band (16-22 Hz)
triggered peripheral stimulation through passive hand opening by a robotic
orthosis and transcranial magnetic stimulation to the respective cortical motor
representation, either synchronously or subsequently. These MI-related paradigms
were compared with paired cortical and peripheral input applied independent of
the brain state. Cortical stimulation resulted in a significant increase in
corticospinal excitability only when applied brain state-dependently and
synchronously to peripheral input. These gains were resistant to a depotentiation
task, revealed a nonlinear evolution of plasticity, and were mediated via the
recruitment of additional corticospinal neurons rather than via synchronization
of neuronal firing. Recruitment of additional corticospinal pathways may be
achieved when cortical and peripheral inputs are applied concurrently, and during
beta-ERD. These findings resemble a gating mechanism and are potentially
important for developing closed-loop brain stimulation for the treatment of hand
paralysis following lesions of the corticospinal tract.SIGNIFICANCE STATEMENT The
activity state of the motor system influences the excitability of corticospinal
pathways to external input. State-dependent interventions harness this property
to increase the connectivity between motor cortex and muscles. These stimulation
protocols modulate the gain of the activated pathways, but not the overall
corticospinal recruitment. In this study, a brain-machine interface paired
peripheral stimulation through passive hand opening with transcranial magnetic
stimulation to the respective cortical motor representation during volitional
beta-band desynchronization. Cortical stimulation resulted in the recruitment of
additional corticospinal pathways, but only when applied brain state-dependently
and synchronously to peripheral input. These effects resemble a gating mechanism
and may be important for the restoration of motor function following lesions of
the corticospinal tract.
PMID- 29335361
TI - Correction to "Discovery of Novel Small-Molecule Inducers of Heme Oxygenase-1
That Protect Human iPSC-Derived Cardiomyocytes from Oxidative Stress".
PMID- 29335360
TI - Activity in the Ventral Medial Prefrontal Cortex Is Necessary for the Therapeutic
Effects of Extinction in Rats.
AB - Poor response and high relapse rates remain problematic in the treatment of
stress-related psychiatric disorders such as depression and post-traumatic stress
disorder. Although mechanisms of pharmacotherapies are intensely studied, little
is known about mechanisms of behavioral therapy that could inform improved
treatments. We have previously demonstrated the therapeutic effects of extinction
learning as a behavioral intervention modeling exposure therapy in rats. In the
present study, we tested the hypothesis that activity in the ventral medial
prefrontal cortex (vmPFC) during extinction is necessary for its therapeutic
effects. The inhibitory Gi-coupled designer receptor exclusively activated by
designer drug CaMKIIalpha-hM4Di was expressed in vmPFC before administering
chronic unpredictable stress (CUS). vmPFC projection neurons were then inhibited
during extinction treatment by administering clozapine-N-oxide. Coping behavior
and cognitive flexibility were assessed 24 h later on the shock-probe defensive
burying test and attentional set-shifting test, respectively. Replicating
previous results, extinction reversed the CUS-induced deficits in coping behavior
and cognitive flexibility. Inhibiting vmPFC during extinction blocked these
therapeutic effects. Further, increasing vmPFC activity with the excitatory Gq
coupled designer receptor exclusively activated by designer drug hM3Dq 24 h
before testing was sufficient to reverse the CUS-induced deficits. CUS reduced
mPFC responsivity, assessed by measuring afferent-evoked field potentials in the
mPFC, and this reduction was reversed by extinction treatment 24 h before
testing. These results demonstrate the necessity of vmPFC activity in the
therapeutic effects of extinction as a model of exposure therapy, and suggest
that increased vmPFC activity induced by extinction is sufficient to produce
lasting plastic changes that underlie its beneficial effects.SIGNIFICANCE
STATEMENT Stress-related psychiatric disorders remain poorly treated.
Psychotherapies can be effective, but their mechanisms remain unknown, hindering
progress toward improved treatment. We used a rat model of behavioral therapy to
identify potential targets for enhancing treatment. Fear extinction as a
therapeutic behavioral intervention reversed stress-induced cognitive dysfunction
and passive coping in rats, modeling components of stress-related psychiatric
disease. Extinction also reversed stress-induced attenuation of mPFC
responsivity. The therapeutic effects were prevented by blocking activity of
glutamatergic neurons in the mPFC during extinction, and were mimicked by
inducing activity in lieu of extinction. Thus, activity and plasticity in the
mPFC underlie the beneficial effects of extinction on cognitive flexibility and
coping behavior compromised by stress, and could be targets to enhance behavioral
therapy.
PMID- 29335362
TI - China: a return to the "kingdom of bicycles"?
PMID- 29335363
TI - Why are there associations between telomere length and behaviour?
AB - Individual differences in telomere length are associated with individual
differences in behaviour in humans and birds. Within the human epidemiological
literature this association is assumed to result from specific behaviour patterns
causing changes in telomere dynamics. We argue that selective adoption-the
hypothesis that individuals with short telomeres are more likely to adopt
specific behaviours-is an alternative worthy of consideration. Selective adoption
could occur either because telomere length directly affects behaviour or because
behaviour and telomere length are both affected by a third variable, such as
exposure to early-life adversity. We present differential predictions of the
causation and selective adoption hypotheses and describe how these could be
tested with longitudinal data on telomere length. Crucially, if behaviour is
causal then it should be associated with differential rates of telomere
attrition. Using smoking behaviour as an example, we show that the evidence that
smoking accelerates the rate of telomere attrition within individuals is
currently weak. We conclude that the selective adoption hypothesis for the
association between behaviour and telomere length is both mechanistically
plausible and, if anything, more compatible with existing empirical evidence than
the hypothesis that behaviour is causal.This article is part of the theme issue
'Understanding diversity in telomere dynamics'.
PMID- 29335364
TI - Experimental manipulation of telomere length: does it reveal a corner-stone role
for telomerase in the natural variability of individual fitness?
AB - Telomeres, the non-coding ends of linear chromosomes, are thought to be an
important mechanism of individual variability in performance. Research suggests
that longer telomeres are indicative of better health and increased fitness;
however, many of these data are correlational and whether these effects are
causal are poorly understood. Experimental tests are emerging in medical and
laboratory-based studies, but these types of experiments are rare in natural
populations, which precludes conclusions at an evolutionary level. At the
crossroads between telomere length and fitness is telomerase, an enzyme that can
lengthen telomeres. Experimental modulation of telomerase activity is a powerful
tool to manipulate telomere length, and to look at the covariation of telomerase,
telomeres and individual life-history traits. Here, we review studies that
manipulate telomerase activity in laboratory conditions and emphasize the
associated physiological and fitness consequences. We then discuss how
telomerase's impact on ageing may go beyond telomere maintenance. Based on this
overview, we then propose several research avenues for future studies to explore
how individual variability in health, reproduction and survival may have
coevolved with different patterns of telomerase activity and expression. Such
knowledge is of prime importance to fully understand the role that telomere
dynamics play in the evolution of animal ageing.This article is part of the theme
issue 'Understanding diversity in telomere dynamics'.
PMID- 29335365
TI - Characterization in humans of in vitro leucocyte maximal telomerase activity
capacity and association with stress.
AB - The goal of this study was to develop and validate a measure of maximal
telomerase activity capacity (mTAC) for use in human studies of telomere biology,
and to determine its association with measures of stress and stress responsivity.
The study was conducted in a population of 28 healthy young women and men who
were assessed serially across two separate days, at multiple time points, and in
response to a standardized laboratory stressor. Venous blood was collected at
each of these multiple assessments, and an in vitro mitogen challenge
(phytohaemagglutinin supplemented with interleukin-2) was used to stimulate
telomerase activity in leucocytes. After first establishing the optimal post
stimulation time course to characterize mTAC, we determined the within-subject
stability and the between-subject variability of mTAC. The major findings of our
study are as follows: (i) the optimal time point to quantify human leucocyte mTAC
appears to be at 72 h after mitogen stimulation; (ii) mTAC exhibits substantial
within-subject stability (correlations were in the range of r 0.68-0.82) and
between-subject variability, with a high intra-class coefficient (0.70),
indicating greater between-subject relative to within-subject variability; (iii)
mTAC is not influenced by situational factors including time of day, cortisol,
acute stress exposure and immune cell distribution in the pre-stimulation blood
sample; and (iv) a significant proportion of the between-subject variability in
mTAC is associated with measures of stress and stress responsivity (mTAC is lower
in subjects reporting higher levels of perceived (chronic) stress and exhibiting
higher psychophysiological stress reactivity). Based collectively on these
findings, it appears that mTAC, as proposed and operationalized, empirically
meets the key criteria to represent a potentially useful individual difference
measure of telomerase activity capacity of human leucocytes.This article is part
of the theme issue 'Understanding diversity in telomere dynamics'.
PMID- 29335367
TI - Evolution of telomere maintenance and tumour suppressor mechanisms across
mammals.
AB - Mammalian species differ dramatically in telomere biology. Species larger than 5
10 kg repress somatic telomerase activity and have shorter telomeres, leading to
replicative senescence. It has been proposed that evolution of replicative
senescence in large-bodied species is an anti-tumour mechanism counteracting
increased risk of cancer due to increased cell numbers. By contrast, small-bodied
species express high telomerase activity and have longer telomeres. To counteract
cancer risk due to longer lifespan, long-lived small-bodied species evolved
additional telomere-independent tumour suppressor mechanisms. Here, we tested the
connection between telomere biology and tumorigenesis by analysing the propensity
of fibroblasts from 18 rodent species to form tumours. We found a negative
correlation between species lifespan and anchorage-independent growth. Small
bodied species required inactivation of Rb and/or p53 and expression of oncogenic
H-Ras to form tumours. Large-bodied species displayed a continuum of phenotypes
requiring additional genetic 'hits' for malignant transformation. Based on these
data we refine the model of the evolution of tumour suppressor mechanisms and
telomeres. We propose that two different strategies evolved in small and large
species because small-bodied species cannot tolerate small tumours that form
prior to activation of the telomere barrier, and must instead use telomere
independent strategies that act earlier, at the hyperplasia stage.This article is
part of the theme issue 'Understanding diversity in telomere dynamics'.
PMID- 29335366
TI - The paternal age at conception effect on offspring telomere length: mechanistic,
comparative and adaptive perspectives.
AB - Telomeres are repeating DNA found at the ends of chromosomes that, in the absence
of restorative processes, shorten with cell replications and are implicated as a
cause of senescence. It appears that sperm telomere length (TL) increases with
age in humans, and as a result offspring of older fathers inherit longer
telomeres. We review possible mechanisms underlying this paternal age at
conception (PAC) effect on TL, including sperm telomere extension due to
telomerase activity, age-dependent changes in the spermatogonial stem cell
population (possibly driven by 'selfish' spermatogonia) and non-causal
confounding. In contrast to the lengthening of TL with PAC, higher maternal age
at conception appears to predict shorter offspring TL in humans. We review
evidence for heterogeneity across species in the PAC effect on TL, which could
relate to differences in statistical power, sperm production rates or testicular
telomerase activity. Finally, we review the hypothesis that the PAC effect on TL
may allow a gradual multi-generational adaptive calibration of maintenance
effort, and reproductive lifespan, to local demographic conditions: descendants
of males who reproduced at a later age are likely to find themselves in an
environment where increased maintenance effort, allowing later reproduction,
represents a fitness improving resource allocation.This article is part of the
theme issue 'Understanding diversity in telomere dynamics'.
PMID- 29335368
TI - In medio stat virtus: unanticipated consequences of telomere dysequilibrium.
AB - The integrity of chromosome ends, or telomeres, depends on myriad processes that
must balance the need to compact and protect the telomeric, G-rich DNA from
detection as a double-stranded DNA break, and yet still permit access to enzymes
that process, replicate and maintain a sufficient reserve of telomeric DNA. When
unable to maintain this equilibrium, erosion of telomeres leads to perturbations
at or near the telomeres themselves, including loss of binding by the telomere
protective complex, shelterin, and alterations in transcription and post
translational modifications of histones. Although the catastrophic consequences
of full telomere de-protection are well described, recent evidence points to
other, less obvious perturbations that arise when telomere length equilibrium is
altered. For example, critically short telomeres also perturb DNA methylation and
histone post-translational modifications at distal sites throughout the genome.
In murine stem cells for example, this dysregulated chromatin leads to
inappropriate suppression of pluripotency regulator factors such as Nanog This
review summarizes these recent findings, with an emphasis on how these genome
wide, telomere-induced perturbations can have profound consequences on cell
function and fate.This article is part of the theme issue 'Understanding
diversity in telomere dynamics'.
PMID- 29335369
TI - The rate of telomere loss is related to maximum lifespan in birds.
AB - Telomeres are highly conserved regions of DNA that protect the ends of linear
chromosomes. The loss of telomeres can signal an irreversible change to a cell's
state, including cellular senescence. Senescent cells no longer divide and can
damage nearby healthy cells, thus potentially placing them at the crossroads of
cancer and ageing. While the epidemiology, cellular and molecular biology of
telomeres are well studied, a newer field exploring telomere biology in the
context of ecology and evolution is just emerging. With work to date focusing on
how telomere shortening relates to individual mortality, less is known about how
telomeres relate to ageing rates across species. Here, we investigated telomere
length in cross-sectional samples from 19 bird species to determine how rates of
telomere loss relate to interspecific variation in maximum lifespan. We found
that bird species with longer lifespans lose fewer telomeric repeats each year
compared with species with shorter lifespans. In addition, phylogenetic analysis
revealed that the rate of telomere loss is evolutionarily conserved within bird
families. This suggests that the physiological causes of telomere shortening, or
the ability to maintain telomeres, are features that may be responsible for, or
co-evolved with, different lifespans observed across species.This article is part
of the theme issue 'Understanding diversity in telomere dynamics'.
PMID- 29335370
TI - Somatic growth and telomere dynamics in vertebrates: relationships, mechanisms
and consequences.
AB - Much telomere loss takes place during the period of most rapid growth when cell
proliferation and potentially energy expenditure are high. Fast growth is linked
to reduced longevity. Therefore, the effects of somatic cell proliferation on
telomere loss and cell senescence might play a significant role in driving the
growth-lifespan trade-off. While different species will have evolved a growth
strategy that maximizes lifetime fitness, environmental conditions encountered
during periods of growth will influence individual optima. In this review, we
first discuss the routes by which altered cellular conditions could influence
telomere loss in vertebrates, with a focus on oxidative stress in both in vitro
and in vivo studies. We discuss the relationship between body growth and telomere
length, and evaluate the empirical evidence that this relationship is generally
negative. We further discuss the potentially conflicting hypotheses that arise
when other factors are taken into account, and the further work that needs to be
undertaken to disentangle confounding variables.This article is part of the theme
issue 'Understanding diversity in telomere dynamics'.
PMID- 29335371
TI - The relationship between telomere length and mortality risk in non-model
vertebrate systems: a meta-analysis.
AB - Telomere length (TL) has become a biomarker of increasing interest within ecology
and evolutionary biology, and has been found to predict subsequent survival in
some recent avian studies but not others. Here, we undertake the first formal
meta-analysis to test whether there is an overall association between TL and
subsequent mortality risk in vertebrates other than humans and model laboratory
rodents. We identified 27 suitable studies and obtained standardized estimates of
the hazard ratio associated with TL from each. We performed a meta-analysis on
these estimates and found an overall significant negative association implying
that short telomeres are associated with increased mortality risk, which was
robust to evident publication bias. While we found that heterogeneity in the
hazard ratios was not explained by sex, follow-up period, maximum lifespan or the
age group of the study animals, the TL-mortality risk association was stronger in
studies using qPCR compared to terminal restriction fragment methodologies. Our
results provide support for a consistent association between short telomeres and
increased mortality risk in birds, but also highlight the need for more research
into non-avian vertebrates and the reasons why different telomere measurement
methods may yield different results.This article is part of the theme issue
'Understanding diversity in telomere dynamics'.
PMID- 29335373
TI - Ectothermic telomeres: it's time they came in from the cold.
AB - We review the evolutionary ecology and genetics of telomeres in taxa that cannot
elevate their body temperature to a preferred level through metabolism but do so
by basking or seeking out a warm environment. This group of organisms contains
all living things on earth, apart from birds and mammals. One reason for our
interest in this synthetic group is the argument that high, stable body
temperature increases the risk of malignant tumours if long, telomerase-restored
telomeres make cells 'live forever'. If this holds true, ectotherms should have
significantly lower cancer frequencies. We discuss to what degree there is
support for this 'anti-cancer' hypothesis in the current literature. Importantly,
we suggest that ectothermic taxa, with variation in somatic telomerase expression
across tissue and taxa, may hold the key to understanding ongoing selection and
evolution of telomerase dynamics in the wild. We further review endotherm
specific effects of growth on telomeres, effects of autotomy ('tail dropping') on
telomere attrition, and costs of maintaining sexual displays measured in telomere
attrition. Finally, we cover plant ectotherm telomeres and life histories in a
separate 'mini review'.This article is part of the theme issue 'Understanding
diversity in telomere dynamics'.
PMID- 29335372
TI - All's well that ends well: why large species have short telomeres.
AB - Among mammal species, almost all life-history traits are strongly size dependent.
This size dependence even occurs at a molecular level. For example, both telomere
length and telomerase expression show a size-dependent threshold. With some
exceptions, species smaller than approximately 2 kg express telomerase, while
species larger than that do not. Among species greater than approximately 5 kg,
telomeres tend to be short-less than 25 kb-while among smaller species, some
species have short and some have long telomeres. Here, we present a model to
explore the role of body size-dependent trade-offs in shaping this threshold. We
assume that selection favours short telomeres as a mechanism to protect against
cancer. At the same time, selection favours long telomeres as a protective
mechanism against DNA damage and replicative senescence. The relative importance
of these two selective forces will depend on underlying intrinsic mortality and
risk of cancer, both of which are size-dependent. Results from this model suggest
that a cost-benefit model for the evolution of telomere length could explain
phylogenetic patterns observed within the Class Mammalia. In addition, the model
suggests a general conceptual framework to think about the role that body size
plays in the evolution of tumour suppressor mechanisms.This article is part of
the theme issue 'Understanding diversity in telomere dynamics'.
PMID- 29335374
TI - Understanding diversity in telomere dynamics.
PMID- 29335375
TI - Reflections on telomere dynamics and ageing-related diseases in humans.
AB - Epidemiological studies have principally relied on measurements of telomere
length (TL) in leucocytes, which reflects TL in other somatic cells. Leucocyte TL
(LTL) displays vast variation across individuals-a phenomenon already observed in
newborns. It is highly heritable, longer in females than males and in individuals
of African ancestry than European ancestry. LTL is also longer in offspring
conceived by older men. The traditional view regards LTL as a passive biomarker
of human ageing. However, new evidence suggests that a dynamic interplay between
selective evolutionary forces and TL might result in trade-offs for specific
health outcomes. From a biological perspective, an active role of TL in ageing
related human diseases could occur because short telomeres increase the risk of a
category of diseases related to restricted cell proliferation and tissue
degeneration, including cardiovascular disease, whereas long telomeres increase
the risk of another category of diseases related to increased proliferative
growth, including major cancers. To understand the role of telomere biology in
ageing-related diseases, it is essential to expand telomere research to newborns
and children and seek further insight into the underlying causes of the variation
in TL due to ancestry and geographical location.This article is part of the theme
issue 'Understanding diversity in telomere dynamics'.
PMID- 29335376
TI - Telomeres and genomic evolution.
AB - The terminal regions of eukaryotic chromosomes, composed of telomere repeat
sequences and sub-telomeric sequences, represent some of the most variable and
rapidly evolving regions of the genome. The sub-telomeric regions are
characterized by segmentally duplicated repetitive DNA elements, interstitial
telomere repeat sequences and families of variable genes. Sub-telomeric repeat
sequence families are shared among multiple chromosome ends, often rendering
detailed sequence characterization difficult. These regions are composed of
constitutive heterochromatin and are subjected to high levels of meiotic
recombination. Dysfunction within telomere repeat arrays, either due to
disruption in the chromatin structure or because of telomere shortening, can lead
to chromosomal fusion and the generation of large-scale genomic rearrangements
across the genome. The dynamic nature of telomeric regions, therefore, provides
functionally useful variation to create genetic diversity, but also provides a
mechanism for rapid genomic evolution that can lead to reproductive isolation and
speciation. This article is part of the theme issue 'Understanding diversity in
telomere dynamics'.This article is part of the theme issue 'Understanding
diversity in telomere dynamics'.
PMID- 29335377
TI - Heritability of telomere variation: it is all about the environment!
AB - Individual differences in telomere length have been linked to survival and
senescence. Understanding the heritability of telomere length can provide
important insight into individual differences and facilitate our understanding of
the evolution of telomeres. However, to gain accurate and meaningful estimates of
telomere heritability it is vital that the impact of the environment, and how
this may vary, is understood and accounted for. The aim of this review is to
raise awareness of this important, but much under-appreciated point. We outline
the factors known to impact telomere length and discuss the fact that telomere
length is a trait that changes with age. We highlight statistical methods that
can separate genetic from environmental effects and control for confounding
variables. We then review how well previous studies in vertebrate populations
including humans have taken these factors into account. We argue that studies to
date either use methodological techniques that confound environmental and genetic
effects, or use appropriate methods but lack sufficient power to fully separate
these components. We discuss potential solutions. We conclude that we need larger
studies, which also span longer time periods, to account for changing
environmental effects, if we are to determine meaningful estimates of the genetic
component of telomere length.This article is part of the theme issue
'Understanding diversity in telomere dynamics'.
PMID- 29335378
TI - Comparison of telomere length measurement methods.
AB - The strengths and limitations of the major methods developed to measure telomere
lengths (TLs) in cells and tissues are presented in this review. These include Q
PCR (Quantitative Polymerase Chain Reaction), TRF (Terminal Restriction Fragment)
analysis, a variety of Q-FISH (Quantitative Fluorescence In Situ Hybridization)
methods, STELA (Single TElomere Length Analysis) and TeSLA (Telomere Shortest
Length Assay). For each method, we will cover information about validation
studies, including reproducibility in independent laboratories, accuracy,
reliability and sensitivity for measuring not only the average but also the
shortest telomeres. There is substantial evidence that it is the shortest
telomeres that trigger DNA damage responses leading to replicative senescence in
mammals. However, the most commonly used TL measurement methods generally provide
information on average or relative TL, but it is the shortest telomeres that
leads to telomere dysfunction (identified by TIF, Telomere dysfunction Induced
Foci) and limit cell proliferation in the absence of a telomere maintenance
mechanism, such as telomerase. As the length of the shortest telomeres is a key
biomarker determining cell fate and the onset of senescence, a new technique
(TeSLA) that provides quantitative information about all the shortest telomeres
will be highlighted.This article is part of the theme issue 'Understanding
diversity in telomere dynamics'.
PMID- 29335379
TI - The role of telomeres in the mechanisms and evolution of life-history trade-offs
and ageing.
AB - Evolutionary biology and biomedicine have seen a surge of recent interest in the
possibility that telomeres play a role in life-history trade-offs and ageing.
Here, I evaluate alternative hypotheses for the role of telomeres in the
mechanisms and evolution of life-history trade-offs and ageing, and highlight
outstanding challenges. First, while recent findings underscore the possibility
of a proximate causal role for telomeres in current-future trade-offs and ageing,
it is currently unclear (i) whether telomeres ever play a causal role in either
and (ii) whether any causal role for telomeres arises via shortening or length
independent mechanisms. Second, I consider why, if telomeres do play a proximate
causal role, selection has not decoupled such a telomere-mediated trade-off
between current and future performance. Evidence suggests that evolutionary
constraints have not rendered such decoupling impossible. Instead, a causal role
for telomeres would more plausibly reflect an adaptive strategy, born of telomere
maintenance costs and/or a function for telomere attrition (e.g. in countering
cancer), the relative importance of which is currently unclear. Finally, I
consider the potential for telomere biology to clarify the constraints at play in
life-history evolution, and to explain the form of the current-future trade-offs
and ageing trajectories that we observe today.This article is part of the theme
issue 'Understanding diversity in telomere dynamics'.
PMID- 29335380
TI - Mitochondrial activity in gametes and uniparental inheritance: a comment on 'What
can we infer about the origin of sex in early eukaryotes?'
PMID- 29335382
TI - The mitochondrial genome, paternal age and telomere length in humans.
AB - Telomere length (TL) in humans is highly heritable and undergoes progressive age
dependent shortening in somatic cells. By contrast, sperm donated by older men
display comparatively long telomeres, presumably because in the male germline,
telomeres become longer with age. This puzzling phenomenon might explain why TL
in the offspring correlates positively with paternal age. The present
communication proposes that mitochondrial DNA polymorphisms and heteroplasmy
cause variation in the production of reactive oxygen species, which, in turn,
mediate age-dependent selection of germ stem cells with long telomeres and hence
sperm with long telomeres. These long telomeres are then inherited by the
offspring. The effect of paternal age on the offspring TL might be an
evolutionarily driven mechanism that helps regulate TL across the human
population.This article is part of the theme issue 'Understanding diversity in
telomere dynamics'.
PMID- 29335383
TI - Response to Ghiselli F et al. (2018).
PMID- 29335384
TI - Predictors of Hemodynamic Improvement and Stabilization Following Intraaortic
Balloon Pump Implantation in Patients With Advanced Heart Failure.
AB - OBJECTIVES: The intraaortic balloon pump (IABP) is currently an essential tool to
improve hemodynamics in patients with advanced heart failure (HF). This study
investigated predictors for hemodynamic improvement or stabilization with IABP
therapy in patients with advanced HF. METHODS: Patients with advanced HF and
hemodynamic deterioration treated with IABP were enrolled in this retrospective
study. Invasive hemodynamics were measured before IABP implantation and 2 weeks
after IABP initiation. Significant degree of hemodynamic improvement was defined
as 30% improvement in all three of the following variables: central venous
pressure (CVP); pulmonary capillary wedge pressure (PCWP); and cardiac index
(CI). Hemodynamic stabilization was counted in patients reaching CVP <12 mm Hg,
PCWP <18 mm Hg, and CI >2.0 L/min/m2 or CI >2.2 L/min/m2 on inotropes. RESULTS:
Ninety-one patients (55 +/- 12 years; 78% males) were evaluated. Seventeen
patients (18.7%) achieved significant hemodynamic improvement, and baseline CVP
>16 mm Hg was associated with this endpoint (P<.05). Thirty-two patients (35.2%)
achieved hemodynamic stabilization; lower baseline heart rate (HR) and PCWP were
associated with this stabilization (P<.05). Patients with HR <92 beats/min and
PCWP <25 mm Hg achieved hemodynamic stabilization more frequently than those
without HR <92 beats/min and PCWP <25 mm Hg (66.7% vs 19.7%; P<.05). CONCLUSION:
Elevated CVP and lower HR and PCWP before IABP initiation help predict high
response to IABP.
PMID- 29335386
TI - Safety and Feasibility of a Novel, Second-Generation Robotic-Assisted System for
Percutaneous Coronary Intervention: First-in-Human Report.
AB - OBJECTIVES: The goal of this study is to evaluate the safety and efficacy of the
second-generation robotic-assisted system CorPath GRX (Corindus) for percutaneous
coronary intervention (PCI). BACKGROUND: The first-generation CorPath 200 robotic
assisted system for PCI is effective, but is limited by the lack of an active
robotic guide-catheter control. The CorPath GRX device enables robotic guide
catheter manipulation, in addition to guidewire and balloon/stent delivery.
However, there have been no clinical data reported with this device. METHODS:
Consecutive patients with demonstrated obstructive coronary artery disease (>70%
stenosis) and clinical indications for PCI were treated with the CorPath GRX
system and enrolled in the study. The two co-primary endpoints were clinical
procedural success (final TIMI 3 flow, and <30% residual stenosis without in
hospital major adverse cardiac event) and device technical success (robotic
clinical procedural success without the need for unplanned manual
assistance/conversion). RESULTS: The study enrolled 40 subjects (65.7 +/- 11.9
years; 72.5% males; 54 lesions) with a high proportion of American College of
Cardiology/American Heart Association type B2/C lesions (77.8%). Clinical
procedural success and device technical success rates were 97.5% (n = 39 of 40)
and 90.0% (n = 36 of 40), respectively. CONCLUSION: The second-generation CorPath
GRX system for robotic-assisted PCI is safe and effective, and achieves high
rates of clinical and technical success in a cohort of patients with complex
coronary disease.
PMID- 29335385
TI - A Transradial Approach of Cardiac Catheterization for Patients on Dialysis.
AB - BACKGROUND: Periprocedural bleeding is associated with increased risk of early
mortality during percutaneous coronary intervention (PCI), especially in patients
on dialysis. A transradial approach (TRA) should be considered for these
patients; however, PCI operators avoid this approach because of the risk of
radial artery occlusion (RAO). The aim of this study is to construct a TRA system
and clarify its safety in patients on dialysis. METHODS: Eighty-eight consecutive
patients on dialysis who underwent cardiac catheterization were prospectively
included in this study and divided according to the access site into either the
TRA group or the transfemoral approach (TFA) group. Radial access was limited in
the opposite side of arteriovenous fistula. The study endpoints were in-hospital
and 30-day mortality rates, puncture-site related bleeding complications, and
other complications. The study safety endpoints were procedure success rate and
RAO rate in the TRA group. RESULTS: Mean patient age was 70.4 +/- 8.5 years. PCI
was performed in 43 patients (48.9%). The TRA and TFA groups included 62 patients
(70.5%) and 26 patients (29.5%), respectively. In-hospital and 30-day mortality
rates were 0.0% in both groups. Puncture-site bleeding rates were 3.8% in the TFA
group and 0.0% in the TRA group (P=.12). Procedural success rate in the TRA group
was 98.4%. Crossover to TFA was necessary in 1 patient due to radial artery
spasm. RAO occurred in 4 patients (6.5%). CONCLUSIONS: Constructed TRA can be
safely used in patients on dialysis. Our study could lead to an increase in TRA
in these patients, which would lead to better prognosis and patient comfort.
PMID- 29335387
TI - Clear Cell Carcinoma of the abdominal wall.
AB - BACKGROUND: Clear cell carcinoma in scars after cesarean section is extremely
rare, with only 22 cases reported in the literature. Management of this condition
needs to be further explored. Here, we report of a patient with clear cell
carcinoma of the abdominal wall that developed 35 years after cesarean section.
CASE REPORT: The material of the study was a group of 61 patients divided into
two groups. Group I - 35 deaf or with profound sensorineural hearing loss
children (the pupils of the deaf and hard of hearing school), aged 5-17 years
(average 9,2 years), 14 males, 21 females, II - control group comprised 26 normal
hearing patients, aged 5-16 years (average 10,4 years), 14 males, 12 females
(patients of Department of Pediatric Otolaryngology, Audiology and Phoniatrics,
Medical University of Lodz). In both groups, exon 2 sequencing of GJB2 gene was
performed. RESULTS: A 58-year-old woman was admitted to our department due to
abdominal pain and a progressively growing mass in the abdominal wall. Based on
biopsy, a preliminary diagnosis of clear cell carcinoma was made. A wide surgical
excision of the tumor with clear margins, hysterectomy with bilateral salpingo
oophorectomy, and abdominal wall reconstruction using synthetic mesh were
performed. The patient was discharged in good condition after fifteen days of
hospitalization. The patient remained recurrence-free 6 months after the
treatment. CONCLUSIONS: T Lack of standardized management of rare malignant
transformations hinders patient care. Due to a growing number of cesarean
deliveries, we can expect clear cell carcinoma prevalence of the abdominal wall
to increase. Therefore, patients and clinicians should attend to any pain,
itching, or change in the size of abdominal wall scars.
PMID- 29335381
TI - The fetal programming of telomere biology hypothesis: an update.
AB - Research on mechanisms underlying fetal programming of health and disease risk
has focused primarily on processes that are specific to cell types, organs or
phenotypes of interest. However, the observation that developmental conditions
concomitantly influence a diverse set of phenotypes, the majority of which are
implicated in age-related disorders, raises the possibility that such
developmental conditions may additionally exert effects via a common underlying
mechanism that involves cellular/molecular ageing-related processes. In this
context, we submit that telomere biology represents a process of particular
interest in humans because, firstly, this system represents among the most
salient antecedent cellular phenotypes for common age-related disorders;
secondly, its initial (newborn) setting appears to be particularly important for
its long-term effects; and thirdly, its initial setting appears to be plastic and
under developmental regulation. We propose that the effects of suboptimal
intrauterine conditions on the initial setting of telomere length and telomerase
expression/activity capacity may be mediated by the programming actions of stress
related maternal-placental-fetal oxidative, immune, endocrine and metabolic
pathways in a manner that may ultimately accelerate cellular dysfunction, ageing
and disease susceptibility over the lifespan. This perspectives paper provides an
overview of each of the elements underlying this hypothesis, with an emphasis on
recent developments, findings and future directions.This article is part of the
theme issue 'Understanding diversity in telomere dynamics'.
PMID- 29335388
TI - Association between clinical stage of oral cancer and expression of
immunohistochemical markers.
AB - AIM: The aim of this study is to demonstrate the possible correlation between the
expression of examined protein markers - p53, EGFR, PCNA, p44/42 in the mass of
the tumor and the clinical stage of disease. MATERIAL: 48 patients of the
Department and Clinic of Oral and Maxillofacial Surgery, Lublin diagnosed with
oral cancer. The control group consisted of 10 patients diagnosed with
leukoplakia lesions in the oral cavity. The methods: Immunohistochemical analysis
using the detection system DAKO K5007 Cat - Dako REAL TM Detection System,
Peroxidase DAB +, Rabbit / Mouse. RESULTS: Based upon the statistical results,
significant correlation between p53 protein and tumor staging; however, a
correlation between the level of expression of EGFR, p44/42, PCNA and staging was
not likewise revealed. CONCLUSIONS: Looking for oral squamous cell carcinoma
markers remains an actual issue. Identification of specific markers of oral
cancer could be used in screening the population, determining prognosis and
response to treatment.
PMID- 29335389
TI - Checklist in colorectal surgery - proposal of experts of the Polish Club of
Coloproctology and National Consultant in general surgery.
AB - A checklist is a collection of information that helps reduce the risk of failure
due to limitations in human memory and attention. In surgery, the first Surgical
Safety Checklist (SSC), created under the supervision of WHO (World Health
Organization), was established in 2007 and covers three stages related to the
patient's stay in the operating theater and operation: 1. Prior to initiation
(induction) of anesthesia; 2. before cutting the skin; 3. before the patient
leaves the operating room Colorectal surgery is particularly at high risk for
complications and relatively high mortality. Elimination or, more likely,
reducing the risk of complications by standardizing perioperative procedures may
be particularly important in this group. The introduction of "dedicated"
colorectal checklist surgery seems to be justified. The checklist proposed by the
authors in colorectal surgery is divided into four stages, in which conscientious
completion of checklists is intended to reduce the potential risk of
complications due to hospitalization and surgical treatment. The presented
checklist is obviously not closed, as a new publications or recommendations
appear, some points may be modified, new issues may be added to the checklist. At
present, however, it is a tool considering the well-known and confirmed elements
of intraoperative procedures, the compliance of which may significantly reduce
the rate of adverse events or surgical complications.
PMID- 29335390
TI - Direct Trocar Insertion with Elevation of the Rectus Sheath in Bariatric Surgery:
A Novel Technique.
AB - INTRODUCTION: Initial trocar entry, the first step in laparoscopic surgery, is
associated with several complications. In morbidly obese patients, initial trocar
placement is associated with a greater number of complications compared to non
obese patients. Materials and Surgical Technique. In this study, we describe our
use of an initial trocar entry technique which is direct trocar insertion with
elevation of the rectus sheath by a single Backhaus towel clamp and we would like
to evaluate the sa fety and efficacy of its administration in bariatric surgery.
DISCUSSION: Our results indicate that gaining initial trocar entry using our
technique leads to successful laparoscopic bariatric surgery. Our technique is a
safe, effective, and reliable first step in successful laparoscopic surgery for
almost all patients, and is only contraindicated in patients with severe
hepatomegaly.
PMID- 29335391
TI - Renal vascularization anomalies in the Polish population.
AB - : The aim of the study was to determine the incidence of renal venous system
congenital anomalies in the Polish population. MATERIAL AND METHOD: Vascular
kidney samples were investigated by means of preparations and X-ray contrasting.
The study the group comprised 281 male and 269 female specimens. RESULTS:
Congenital anomalies were diagnosed in 186 patients (33 8% of all cases), and
they were more frequent in men than in women, albeit that difference was non
significant. The following anomalies were most commonly observed: multiple venous
variations on the right side (20.4%), retroaortic course of the left renal vein
(4.2%), and circumaortic venous ring of the left renal vein (3.8%). Other
anomalies were diagnosed in 1%-2% of cases. CONCLUSIONS: Awareness and
preoperative assessment of the venous system before abdominal aortic surgery,
isolated collection of renal venous blood samples, and urological or kidney
transplantation procedures is essential.
PMID- 29335392
TI - Cytoreductive surgery and HIPEC in the treatment of peritoneal metastases of
sarcomas and other rare malignancies.
AB - .................................... Cytoreductive surgery and HIPEC in the
treatment of peritoneal metastases of sarcomas and other rare malignancies.
PMID- 29335393
TI - Peritoneal metastases of colorectal origin - cytoreductive surgery and
hyperthermic intraperitoneal chemotherapy (HIPEC). The financial aspect.
AB - The incidence of peritoneal carcinomatosis of colorectal cancer amounts to 5%-15%
for synchronous metastases and as much as 40% in cases of local recurrence. Best
results are obtained for cytoreductive surgery combined with hyperthermic
intraperitoneal chemotherapy (HIPEC). This treatment offers much better outcomes,
leading to 5-year survival rates of as much as 30%-50%. The procedures require
significant experience in abdominal surgery, are time-consuming (mean duration of
the procedure ranging from 6 to 8 hours) and are burdened by complications that
are due not only to the procedure itself but also to the intraperitoneal
administration of the cytostatic drug at elevated temperature (41.5 degrees C).
After the procedure, patients are required to be admitted to intensive care units
due to potential complications associated with the extent and duration of the
procedure as well as chemotherapy administered in hyperthermia. Postoperative
management of these patients requires appropriate experience of the entire
medical and nursing team. Cytoreductive surgeries combined with HIPEC as highly
specialized medical procedures should be assessed for their potential long-term
benefits and their costs should be appropriately calculated with consideration to
realistic reimbursement rates. Realistic valuation and reimbursement covering the
overall average cost of the procedure is recommended by the National Consultant
in Surgical Oncology as well as the ESMO consensus guidelines.
PMID- 29335394
TI - Landscape of oncoplastic breast surgery across Poland.
AB - Oncoplastic and reconstructive techniques are essential tools in the
armamentarium of contemporary breast surgeons. The aim of the study was to
identify oncoplastic reconstructive patterns in breast cancer centers across
Poland. A questionnaire of 18 questions was sent by email to the members of the
Polish Society of Surgical Oncology and the Polish Society of Plastic,
Reconstructive and Esthetic Surgery via their dedicated websites. The numbers of
breast cancer patients operated on in each center ranged from 120 to 904 per
year. Breast-conserving surgery (BCS) predominated in all but one center (range
50-70%). Immediate breast reconstructions (IBR) accounted for 6-42% of
procedures, The most frequent type of IBR was either a two-stage expander
followed by a permanent implant or one-stage implant- based with or without
synthetic mesh. The most frequent type of delayed breast reconstruction (DBR) was
a two-stage expander followed by implant-based reconstruction. None of the
surveyed cancer centers performed free flap reconstruction. Deep inferior
epigastric perforator (DIEP) flaps were performed in the plastic surgery
department. Reconstructions based on pedicled flaps were performed in cancer
centers. Acellular dermal matrices (ADM) and fat transfer were used in selected
centers. In the clinical scenario of adjuvant radiotherapy, delayed breast
reconstruction was favored. The full range of oncoplastic BCS was performed.
Patient-reported outcome measures (PROM) and complications were assessed. Our
findings can act as a platform for further improvement in skills, certification,
data collection and audit, including patient reported expectation measures. There
is also an urgent need to address pan-European inconsistencies in procedural
reimbursement.
PMID- 29335395
TI - Predictors of recanalization after endovascular treatment of posterior
circulation aneurysms.
AB - INTRODUCTION: Posterior circulation aneurysms account for approximately 30% of
all intracranial aneurysms, and their rupture often causes aneurysmal
subarachnoid hemorrhage (aSAH). Because surgical treatment of posterior
circulation aneurysms is difficult, endovascular treatment is commonly indicated.
However, simple coil embolization is associated with a high rate of
recanalization. Our goal was to investigate morphometric aneurysmal features
assessed on pre-embolization computed tomography angiography (CTA) as predictors
of recanalization in patients with posterior circulation aneurysms. MATERIAL AND
METHODS: We retrospectively analyzed data of 24 patients who underwent coil
embolization due to rupture of saccular posterior circulation aneurysms. The
morphometric features of aneurysms were measured based on pre-embolization 3D-CTA
aneurysm models, and aneurysmal size and volume were measured on digital
subtraction angiography (DSA) images. The effectiveness of initial endovascular
treatment was determined visually with the modified Raymond Roy classification
directly after embolization and on follow-up DSAs. Recanalization was diagnosed
when, compared to the primary embolization aneurysm appearance, compaction and
filling of the aneurysm occurred. Statistical analysis was performed with
Statistica 13.1 software. RESULTS: Higher maximal aneurysm height perpendicular
to the aneurysmal neck was associated with a greater aneurysm recanalization risk
(12.12+/-5.13mm vs. 7.41+/-3.97mm, p=0.039), and this relationship remained
significant after adjustment for patient's age, sex and aneurysm localization
(OR=1.26, 95%CI: 1.01-1.60, p=0.047). Maximal aneurysm height perpendicular to
the aneurysmal neck distinguished well between recanalized and non-recanalized
aneurysms (AUC=0.755, 95%CI: 0.521- 0.989, p=0.033). CONCLUSIONS: Predictors of
aneurysm recanalization can help choose best endovascular treatment strategies,
which could reduce complication rates.
PMID- 29335396
TI - Barogenic rupture of esophagus (Boerhaave syndrome) as diagnostic and therapeutic
challenge requiring rapid and effective interdisciplinary cooperation - case
report.
AB - We describe a 47-year-old male who was admitted to our centre from a local
emergency unit with septic shock due to suspected Boerhaave syndrome. After the
diagnosis was confirmed, the patient underwent emergency surgery.
Postoperatively, the patient had symptoms of acute alcoholic delirium, and
developed an oesophagomediastinal fistula as the most serious local complication.
Successful conservative treatment enabled complete healing of the fistula,
leading to patient recovery. No late complications like oesophageal stenosis were
found at 6 months from discharge.
PMID- 29335397
TI - Pediatric Renal Transplantation: Focus on Current Transition Care and Proposal of
the "RISE to Transition" Protocol.
AB - The transition from pediatric to adult medical services is an important time in
the life of an adolescent or young adult with a renal transplant. Failure of
proper transition can lead to medical non-adherence and subsequent loss of graft
and/or return to dialysis. The aim of this study was to conduct a systematic
review and survey to assess the challenges and existing practices in transition
of renal transplant recipient children to adult services, and to develop a
transition protocol. We conducted a literature review and performed a survey of
pediatric nephrologists across the United States to examine the current state of
transition care. A structured transition protocol was developed based on these
results. Our literature review revealed that a transition program has a positive
impact on decline in renal function and acute rejection episodes, and may improve
long-term graft outcomes in pediatric kidney transplant patients. With a response
rate of 40% (60/150) from nephrologists in 56% (49/87) of centers, our survey
shows inconsistent use of validated tools despite their availability, inefficient
communication between teams, and lack of use of dedicated clinics. To address
these issues, we developed the "RISE to Transition" protocol, which relies on 4
competency areas: Recognition, Insight, Self-reliance, and Establishment of
healthy habits. The transition program decreases acute graft rejection episodes,
and the main challenges in transition care are the communication gap between
health care providers and inconsistent use of transition tools. Our RISE to
transition protocol incorporates transition tools, defines personnel, and aims to
improve communication between teams.
PMID- 29335398
TI - Massive Post-Obstructive Diuresis.
AB - BACKGROUND The purpose of presenting this case is to demonstrate the degree to
which the kidney is capable of selectively excreting a massive load of sodium and
water when challenged with both of these, without altering the plasma levels of
other ions. CASE REPORT An 8-year-old boy was admitted in severe renal failure.
Workup demonstrated a high grade obstruction of a single kidney. Following
dialysis, the patient underwent surgery to correct the obstruction and he
developed post-obstructive diuresis. Within one week he was receiving 34 liters
of essentially 1/2 Na by IV and by mouth and was excreting 70% of his filtered
load of water and 50% of his filtered load of sodium. As soon as the administered
fluids and Na were cut back, the kidney responded appropriately. CONCLUSIONS
While post-obstructive diuresis is a real phenomenon, very frequently it is
magnified by forcing diuresis with the administration of too much water. These
patients are best treated by administering fluids to equal output for two to
three days and then gradually cutting back on fluid intake. If the kidney
responds appropriately, then fluids can be given as the patient requests.
PMID- 29335399
TI - Prevalence and Causes of Visual Impairment in Adults in Binhu District, Wuxi,
China.
AB - BACKGROUND Previously reported data has guided the treatment and prevention of
blindness. This study aimed to evaluate the current prevalence and causes of
visual impairment among adults who were 50 years old and older in the Binhu
District of Wuxi City, China. MATERIAL AND METHODS A randomized sample of
stratified clusters was used to analyze individuals from 30 basic sampling units
in Wuxi Binhu District. Visual impairment was defined according to World Health
Organization (WHO) standards. RESULTS A total of 6725 people who were at least 50
years old participated in this study. According to WHO standards, bilateral low
vision and blindness prevalence were both higher in women than in men (low
vision: 6.5% vs. 5.2%; and blindness: 1.4% vs. 0.8%; P=0.022 and P=0.039,
respectively). The incidence of bilateral visual impairment increased
significantly with age (P<0.001 and P<0.001, respectively). Further studies
showed that the main causes of bilateral low vision were cataract, high myopic
macular degeneration (MMD), and age-related macular degeneration (AMD). The main
causes of bilateral blindness were cataract, MMD, and eye loss/atrophy, while the
main causes of monocular low vision were cataract, MD, and AMD. The main causes
of monocular blindness were cataract, eye loss/atrophy, and AMD. CONCLUSIONS The
prevalence of low vision and blindness remains high in the Binhu District of Wuxi
City in China, especially among older women. In our study, cataracts were the
leading cause of visual impairment. Our study highlights that some efforts should
be initiated to prevent and treat blindness and low vision. Additional causes of
visual impairment were MMD, AMD, and eye loss/atrophy.
PMID- 29335401
TI - Author Correction: Spiraling pathways of global deep waters to the surface of the
Southern Ocean.
AB - The original version of this Article contained errors in Fig. 6. In panel a, the
grey highlights obscured the curves for CESM, CM2.6 and SOSE, and the labels
indicating SWIR, KP, MR, PAR, and DP were inadvertently omitted. These have now
been corrected in both the PDF and HTML versions of the Article.
PMID- 29335400
TI - Causal associations between risk factors and common diseases inferred from GWAS
summary data.
AB - Health risk factors such as body mass index (BMI) and serum cholesterol are
associated with many common diseases. It often remains unclear whether the risk
factors are cause or consequence of disease, or whether the associations are the
result of confounding. We develop and apply a method (called GSMR) that performs
a multi-SNP Mendelian randomization analysis using summary-level data from genome
wide association studies to test the causal associations of BMI, waist-to-hip
ratio, serum cholesterols, blood pressures, height, and years of schooling
(EduYears) with common diseases (sample sizes of up to 405,072). We identify a
number of causal associations including a protective effect of LDL-cholesterol
against type-2 diabetes (T2D) that might explain the side effects of statins on
T2D, a protective effect of EduYears against Alzheimer's disease, and
bidirectional associations with opposite effects (e.g., higher BMI increases the
risk of T2D but the effect of T2D on BMI is negative).
PMID- 29335402
TI - A partially-open inward-facing intermediate conformation of LeuT is associated
with Na+ release and substrate transport.
AB - Neurotransmitter:sodium symporters (NSS), targets of antidepressants and
psychostimulants, clear neurotransmitters from the synaptic cleft through sodium
(Na+)-coupled transport. Substrate and Na+ are thought to be transported from the
extracellular to intracellular space through an alternating access mechanism by
coordinated conformational rearrangements in the symporter that alternately
expose the binding sites to each side of the membrane. However, the mechanism by
which the binding of ligands coordinates conformational changes occurring on
opposite sides of the membrane is not well understood. Here, we report the use of
single-molecule fluorescence resonance energy transfer (smFRET) techniques to
image transitions between distinct conformational states on both the
extracellular and intracellular sides of the prokaryotic NSS LeuT, including
partially open intermediates associated with transport activity. The nature and
functional context of these hitherto unidentified intermediate states shed new
light on the allosteric mechanism that couples substrate and Na+ symport by the
NSS family through conformational dynamics.
PMID- 29335403
TI - Floats with bio-optical sensors reveal what processes trigger the North Atlantic
bloom.
AB - The North Atlantic bloom corresponds to a strong seasonal increase in
phytoplankton that produces organic carbon through photosynthesis. It is still
debated what physical and biological conditions trigger the bloom, because
comprehensive time series of the vertical distribution of phytoplankton biomass
are lacking. Vertical profiles from nine floats that sampled the waters of the
North Atlantic every few days for a couple of years reveal that phytoplankton
populations start growing in early winter at very weak rates. A proper bloom with
rapidly accelerating population growth rates instead starts only in spring when
atmospheric cooling subsides and the mixed layer rapidly shoals. While the weak
accumulation of phytoplankton in winter is crucial to maintaining a viable
population, the spring bloom dominates the overall seasonal production of organic
carbon.
PMID- 29335404
TI - Publisher Correction: Second-order spectral lineshapes from charged interfaces.
AB - The original version of this Article contained an error in Equation 3b. A ' + '
sign incorrectly appeared instead of a '-' sign in the denominator of the right
hand side of the equation and incorrectly read:[Formula: see text]The correct
form of the equation is as follows:[Formula: see text]This has now been corrected
in both the PDF and HTML versions of the Article.
PMID- 29335405
TI - Author Correction: Myoblasts and macrophages are required for therapeutic
morpholino antisense oligonucleotide delivery to dystrophic muscle.
AB - In the original version of this Article, financial support was not fully
acknowledged. The PDF and HTML versions of the Article have now been corrected to
include support from the CRI Light Microscopy and Image Analysis Core.
PMID- 29335406
TI - Thalidomide plus prednisone with or without danazol therapy in myelofibrosis: a
retrospective analysis of incidence and durability of anemia response.
AB - Low-dose thalidomide and prednisone alone or combined are effective therapies in
some persons with primary myelofibrosis (PMF) and anemia with or with RBC
transfusion dependence. Danazol is also effective in some persons with PMF and
anemia. Responses to these drugs are typically incomplete and not sustained. It
is unclear whether adding danazol to thalidomide and prednisone would improve
efficacy. We retrospectively compared the outcomes of 88 subjects with PMF and
anemia receiving thalidomide and prednisone without (n = 46) or with danazol (n =
42). The primary end point was anemia response, which was 71% (95% confidence
interval (CI), 57, 85%) in subjects receiving thalidomide/prednisone/danazol
compared with 46% (32, 60%; P = 0.014) in those receiving thalidomide/prednisone.
Response rates in subjects who were RBC transfusion dependent was also higher in
the danazol cohort (61% (38, 84%)) vs. 25% (6, 44%); P = 0.024). Time to response
was rapid (median, 2 months (range, 1-11 months)) and similar between the
cohorts. Response duration was longer in the thalidomide/prednisone/danazol
cohort (HR 2.18 (1.18-5.42); P = 0.019). Adverse effects were mild and similar
between the cohorts. In conclusion, thalidomide/prednisone/danazol seems superior
to thalidomide/prednisone in persons with PMF and anemia. Our conclusion requires
confirmation in a randomized trial.
PMID- 29335407
TI - Radical asymmetric intramolecular alpha-cyclopropanation of aldehydes towards
bicyclo[3.1.0]hexanes containing vicinal all-carbon quaternary stereocenters.
AB - The development of a general catalytic method for the direct and stereoselective
construction of cyclopropanes bearing highly congested vicinal all-carbon
quaternary stereocenters remains a formidable challenge in chemical synthesis.
Here, we report an intramolecular radical cyclopropanation of unactivated alkenes
with simple alpha-methylene group of aldehydes as C1 source via a Cu(I)/secondary
amine cooperative catalyst, which enables the single-step construction of
bicyclo[3.1.0]hexane skeletons with excellent efficiency, broad substrate scope
covering various terminal, internal alkenes as well as diverse (hetero)aromatic,
alkenyl, alkyl-substituted geminal alkenes. Moreover, this reaction has been
successfully realized to an asymmetric transformation, providing an attractive
approach for the construction of enantioenriched bicyclo[3.1.0]hexanes bearing
two crucial vicinal all-carbon quaternary stereocenters with good to excellent
enantioselectivity. The utility of this method is illustrated by facile
transformations of the products into various useful chiral synthetic
intermediates. Preliminary mechanistic studies support a stepwise radical process
for this formal [2 + 1] cycloaddition.
PMID- 29335408
TI - Escape from thymic deletion and anti-leukemic effects of T cells specific for
hematopoietic cell-restricted antigen.
AB - Whether hematopoietic cell-restricted distribution of antigens affects the degree
of thymic negative selection has not been investigated in detail. Here, we show
that T cells specific for hematopoietic cell-restricted antigens (HRA) are not
completely deleted in the thymus, using the mouse minor histocompatibility
antigen H60, the expression of which is restricted to hematopoietic cells. As a
result, low avidity T cells escape from thymic deletion. This incomplete thymic
deletion occurs to the T cells developing de novo in the thymus of H60-positive
recipients in H60-mismatched bone marrow transplantation (BMT). H60-specific
thymic deletion escapee CD8+ T cells exhibit effector differentiation potentials
in the periphery and contribute to graft-versus-leukemia effects in the
recipients of H60-mismatched BMT, regressing H60+ hematological tumors. These
results provide information essential for understanding thymic negative selection
and developing a strategy to treat hematological tumors.
PMID- 29335409
TI - Electric-field control of anomalous and topological Hall effects in oxide bilayer
thin films.
AB - One of the key goals in spintronics is to tame the spin-orbit coupling (SOC) that
links spin and motion of electrons, giving rise to intriguing magneto-transport
properties in itinerant magnets. Prominent examples of such SOC-based phenomena
are the anomalous and topological Hall effects. However, controlling them with
electric fields has remained unachieved since an electric field tends to be
screened in itinerant magnets. Here we demonstrate that both anomalous and
topological Hall effects can be modulated by electric fields in oxide
heterostructures consisting of ferromagnetic SrRuO3 and nonmagnetic SrIrO3. We
observe a clear electric field effect only when SrIrO3 is inserted between SrRuO3
and a gate dielectric. Our results establish that strong SOC of nonmagnetic
materials such as SrIrO3 is essential in electrical tuning of these Hall effects
and possibly other SOC-related phenomena.
PMID- 29335410
TI - Abnormal phase transition between two-dimensional high-density liquid crystal and
low-density crystalline solid phases.
AB - Some two-dimensional liquid systems are theoretically predicted to have an
anomalous phase transition due to unique intermolecular interactions, for example
the first-order transition between two-dimensional high-density water and low
density amorphous ice. However, it has never been experimentally observed, to the
best of our knowledge. Here we report an entropy-driven phase transition between
a high-density liquid crystal and low-density crystalline solid, directly
observed by scanning tunneling microscope in carbon monoxide adsorbed on Cu(111).
Combined with first principle calculations, we find that repulsive dipole-dipole
interactions between carbon monoxide molecules lead to unconventional
thermodynamics. This finding of unconventional thermodynamics in two-dimensional
carbon monoxide not only provides a platform to study the fundamental principles
of anomalous phase transitions in two-dimensional liquids at the atomic scale,
but may also help to design and develop more efficient copper-based catalysis.
PMID- 29335411
TI - Reconfiguring crystal and electronic structures of MoS2 by substitutional doping.
AB - Doping of traditional semiconductors has enabled technological applications in
modern electronics by tailoring their chemical, optical and electronic
properties. However, substitutional doping in two-dimensional semiconductors is
at a comparatively early stage, and the resultant effects are less explored. In
this work, we report unusual effects of degenerate doping with Nb on structural,
electronic and optical characteristics of MoS2 crystals. The doping readily
induces a structural transformation from naturally occurring 2H stacking to 3R
stacking. Electronically, a strong interaction of the Nb impurity states with the
host valence bands drastically and nonlinearly modifies the electronic band
structure with the valence band maximum of multilayer MoS2 at the Gamma point
pushed upward by hybridization with the Nb states. When thinned down to
monolayers, in stark contrast, such significant nonlinear effect vanishes,
instead resulting in strong and broadband photoluminescence via the formation of
exciton complexes tightly bound to neutral acceptors.
PMID- 29335412
TI - Phosphorylation-induced conformation of beta2-adrenoceptor related to arrestin
recruitment revealed by NMR.
AB - The C-terminal region of G-protein-coupled receptors (GPCRs), stimulated by
agonist binding, is phosphorylated by GPCR kinases, and the phosphorylated GPCRs
bind to arrestin, leading to the cellular responses. To understand the mechanism
underlying the formation of the phosphorylated GPCR-arrestin complex, we
performed NMR analyses of the phosphorylated beta2-adrenoceptor (beta2AR) and the
phosphorylated beta2AR-beta-arrestin 1 complex, in the lipid bilayers of
nanodisc. Here we show that the phosphorylated C-terminal region adheres to
either the intracellular side of the transmembrane region or lipids, and that the
phosphorylation of the C-terminal region allosterically alters the conformation
around M2155.54 and M2796.41, located on transemembrane helices 5 and 6,
respectively. In addition, we found that the conformation induced by the
phosphorylation is similar to that corresponding to the beta-arrestin-bound
state. The phosphorylation-induced structures revealed in this study propose a
conserved structural motif of GPCRs that enables beta-arrestin to recognize
dozens of GPCRs.
PMID- 29335413
TI - Heliconical smectic phases formed by achiral molecules.
AB - Chiral symmetry breaking in soft matter is a hot topic of current research.
Recently, such a phenomenon was found in a fluidic phase showing orientational
order of molecules-the nematic phase; although built of achiral molecules, the
phase can exhibit structural chirality-average molecular direction follows a
short-pitch helix. Here, we report a series of achiral asymmetric dimers with an
odd number of atoms in the spacer, which form twisted structures in nematic as
well as in lamellar phases. The tight pitch heliconical nematic (NTB) phase and
heliconical tilted smectic C (SmCTB) phase are formed. The formation of a variety
of helical structures is accompanied by a gradual freezing of molecular rotation.
In the lowest temperature smectic phase, HexI, the twist is expressed through the
formation of hierarchical structure: nanoscale helices and mesoscopic helical
filaments. The short-pitch helical structure in the smectic phases is confirmed
by resonant X-ray measurements.
PMID- 29335414
TI - Evolutionary history of Coleoptera revealed by extensive sampling of genes and
species.
AB - Beetles (Coleoptera) are the most diverse and species-rich group of insects, and
a robust, time-calibrated phylogeny is fundamental to understanding
macroevolutionary processes that underlie their diversity. Here we infer the
phylogeny and divergence times of all major lineages of Coleoptera by analyzing
95 protein-coding genes in 373 beetle species, including ~67% of the currently
recognized families. The subordinal relationships are strongly supported as
Polyphaga (Adephaga (Archostemata, Myxophaga)). The series and superfamilies of
Polyphaga are mostly monophyletic. The species-poor Nosodendridae is robustly
recovered in a novel position sister to Staphyliniformia, Bostrichiformia, and
Cucujiformia. Our divergence time analyses suggest that the crown group of extant
beetles occurred ~297 million years ago (Mya) and that ~64% of families
originated in the Cretaceous. Most of the herbivorous families experienced a
significant increase in diversification rate during the Cretaceous, thus
suggesting that the rise of angiosperms in the Cretaceous may have been an
'evolutionary impetus' driving the hyperdiversity of herbivorous beetles.
PMID- 29335415
TI - USP48 restrains resection by site-specific cleavage of the BRCA1 ubiquitin mark
from H2A.
AB - BRCA1-BARD1-catalyzed ubiquitination of histone H2A is an important regulator of
the DNA damage response, priming chromatin for repair by homologous
recombination. However, no specific deubiquitinating enzymes (DUBs) are known to
antagonize this function. Here we identify ubiquitin specific protease-48 (USP48)
as a H2A DUB, specific for the C-terminal BRCA1 ubiquitination site. Detailed
biochemical analysis shows that an auxiliary ubiquitin, an additional ubiquitin
that itself does not get cleaved, modulates USP48 activity, which has possible
implications for its regulation in vivo. In cells we reveal that USP48
antagonizes BRCA1 E3 ligase function and in BRCA1-proficient cells loss of USP48
results in positioning 53BP1 further from the break site and in extended
resection lengths. USP48 repression confers a survival benefit to cells treated
with camptothecin and its activity acts to restrain gene conversion and mutagenic
single-strand annealing. We propose that USP48 promotes genome stability by
antagonizing BRCA1 E3 ligase function.
PMID- 29335416
TI - Lack of pronounced changes in the expression of fatty acid handling proteins in
adipose tissue and plasma of morbidly obese humans.
AB - BACKGROUND/OBJECTIVES: Fatty acid handling proteins are involved in the process
of accumulation of lipids in different fat tissue depots. Thus, the aim of the
study was to estimate the expression of both fatty acid transport and binding
proteins in the subcutaneous (SAT) and visceral adipose tissue (VAT) of patients
with morbid obesity without metabolic syndrome, as well as the plasma
concentrations of these transporters. SUBJECTS/METHODS: Protein (Western
blotting) and mRNA (Real-time PCR) expression of selected fatty acid handling
proteins was assessed in the visceral and subcutaneous adipose tissue of 30
patients with morbid obesity. The control group consisted of 10 lean age-matched
patients. Plasma levels of fatty acid protein transporters were also evaluated
using ELISA method. Moreover, total plasma fatty acid composition and
concentration was determined by gas-liquid chromatography (GLC). RESULTS:
Significant increase in fatty acid translocase (FAT/CD36) mRNA (P = 0.03) and
plasmalemmal (P = 0.01) expression was observed in VAT of patients with morbid
obesity vs. lean subjects together with elevation of lipoprotein lipase (LPL), as
well as peroxisome proliferator-activated receptor gamma (PPARgamma) in both
examined compartments of adipose tissue. Moreover, in obese subjects plasma
concentration of RBP4 was markedly elevated (P = 0.04) and sCD36 level presented
a tendency for an increase (P = 0.08) with concomitant lack of changes in FABP4
concentration (P > 0.05). CONCLUSIONS: Fatty acid transport into adipocytes may
be, at least in part, related to the increased expression of FAT/CD36 in the VAT
of morbidly obese patients, which is accompanied by augmented expression of LPL,
as well as PPARgamma. Probably, alternations in plasma concentrations of RBP4 and
sCD36 in obese patients are associated with "unhealthy" fat distribution.
PMID- 29335417
TI - Europe's lost forests: a pollen-based synthesis for the last 11,000 years.
AB - 8000 years ago, prior to Neolithic agriculture, Europe was mostly a wooded
continent. Since then, its forest cover has been progressively fragmented, so
that today it covers less than half of Europe's land area, in many cases having
been cleared to make way for fields and pasture-land. Establishing the origin of
Europe's current, more open land-cover mosaic requires a long-term perspective,
for which pollen analysis offers a key tool. In this study we utilise and compare
three numerical approaches to transforming pollen data into past forest cover,
drawing on >1000 14C-dated site records. All reconstructions highlight the
different histories of the mixed temperate and the northern boreal forests, with
the former declining progressively since ~6000 years ago, linked to forest
clearance for agriculture in later prehistory (especially in northwest Europe)
and early historic times (e.g. in north central Europe). In contrast, extensive
human impact on the needle-leaf forests of northern Europe only becomes
detectable in the last two millennia and has left a larger area of forest in
place. Forest loss has been a dominant feature of Europe's landscape ecology in
the second half of the current interglacial, with consequences for carbon
cycling, ecosystem functioning and biodiversity.
PMID- 29335418
TI - Gender-specific association of early age-related macular degeneration with
systemic and genetic factors in a Japanese population.
AB - The Tsuruoka Metabolomics Cohort Study included subjects aged 35-74 years from
participants in annual health check-up programs in Tsuruoka, Japan. The gender
specific associations of early age-related macular degeneration (AMD) with
systemic and genetic factors was assessed cross-sectionally. Of these, 3,988
subjects had fundus photographs of sufficient quality, and early AMD was present
in 12.3% and 10.3% of men and women, respectively. In men, higher levels of high
density lipoprotein cholesterol and lower levels of triglycerides were associated
with increased odds of having early AMD after adjusting for potential risk
factors (for each 1 mmol/L increase, odds ratio [OR]: 1.61 and 0.78, 95%
confidence interval [CI]: 1.17-2.23 and 0.64-0.96, respectively). In women,
higher levels of total cholesterol and low-density lipoprotein cholesterol were
associated with increased risk of having early AMD (OR: 1.21 and 1.26, 95% CI:
1.01-1.44 and 1.03-1.53, respectively). Sub-analysis demonstrated that women with
ARMS2 A69S polymorphisms had a stronger risk for early AMD (OR: 3.25, 95% CI:
2.10-5.04) than men (OR: 1.65, 95% CI: 1.02-2.69). Differential associations of
early AMD with both systemic and genetic factors by sex were demonstrated in a
Japanese cohort, which suggests that disease process of early AMD could be
different by sex.
PMID- 29335419
TI - A Global View of Transcriptome Dynamics During Male Floral Bud Development in
Populus tomentosa.
AB - To obtain a comprehensive overview of the dynamic transcriptome during male
floral bud development in Populus tomentosa, high-throughput RNA-seq was
conducted during eight flowering-related stages. Among the 109,212 de novo
assembled unigenes, 6,959 were differentially expressed during the eight stages.
The overrepresented classed of genes identified by Gene Ontology (GO) enrichment
included 'response to environmental stimuli' and 'plant-type spore development'.
One-third of the differentially expressed genes were transcription factors (TFs).
Several genes and gene families were analyzed in depth, including MADS-box TFs,
Squamosa promoter binding protein-like family, receptor-like kinases, FLOWERING
LOCUS T/TERMINAL-FLOWER-LIKE 1 family, key genes involved in anther and tapetum
development, as well as LEAFY, WUSCHEL and CONSTANS. The results provided new
insights into the roles of these and other well known gene families during the
annual flowering cycle. To explore the mechanisms regulating poplar flowering, a
weighted gene co-expression network was constructed using 98 floral-related genes
involved in flower meristem identity and flower development. Many modules of co
expressed genes and hub genes were identified, such as APETALA1 and HUA1. This
work provides many new insights on the annual flowering cycle in a perennial
plant, and a major new resource for plant biology and biotechnology.
PMID- 29335420
TI - Lamina Cribrosa Morphology Predicts Progressive Retinal Nerve Fiber Layer Loss In
Eyes with Suspected Glaucoma.
AB - Although early diagnosis and treatment reduce the risk of blindness from
glaucoma, the decision on whether or not to begin treatment in patients with
suspected glaucoma is often a dilemma because the majority of patients never
develop definite glaucoma. A growing body of evidences suggests that posterior
bowing of the lamina cribrosa (LC) is the earliest structural change preceding
the retinal nerve fiber layer (RNFL) loss in glaucomatous optic neuropathy. Based
on this notion, we conducted a prospective study enrolling 87 eyes suspected of
having glaucoma to investigate whether the future rate of RNFL loss is associated
with the baseline LC curve evaluated by measuring the LC curve index (LCCI) using
enhanced depth imaging optical coherence tomography. A faster rate of RNFL loss
was significantly associated with greater LCCI (P < 0.001;standardized
coefficient beta = -0.392), older age (P = 0.008;beta = -0.314), and greater
vertical cup-to-disc ratio (P = 0.040;beta = -0.233). Assessment of LC morphology
may help predict the disease outcome in eyes with suspected glaucoma.
PMID- 29335421
TI - Hydroacoustics as a tool to examine the effects of Marine Protected Areas and
habitat type on marine fish communities.
AB - Hydroacoustic technologies are widely used in fisheries research but few studies
have used them to examine the effects of Marine Protected Areas (MPAs). We
evaluate the efficacy of hydroacoustics to examine the effects of closure to
fishing and habitat type on fish populations in the Cabo Pulmo National Park
(CPNP), Mexico, and compare these methods to Underwater Visual Censuses (UVC).
Fish density, biomass and size were all significantly higher inside the CPNP
(299%, 144% and 52% respectively) than outside in non-MPA control areas. These
values were much higher when only accounting for the reefs within the CPNP
(4715%, 6970% and 97% respectively) highlighting the importance of both habitat
complexity and protection from fishing for fish populations. Acoustic estimates
of fish biomass over reef-specific sites did not differ significantly from those
estimated using UVC data, although acoustic densities were less due to higher
numbers of small fish recorded by UVC. There is thus considerable merit in
nesting UVC surveys, also providing species information, within hydroacoustic
surveys. This study is a valuable starting point in demonstrating the utility of
hydroacoustics to assess the effects of coastal MPAs on fish populations,
something that has been underutilised in MPA design, formation and management.
PMID- 29335422
TI - Lifetime-preserving reference models for characterizing spreading dynamics on
temporal networks.
AB - To study how a certain network feature affects processes occurring on a temporal
network, one often compares properties of the original network against those of a
randomized reference model that lacks the feature in question. The randomly
permuted times (PT) reference model is widely used to probe how temporal features
affect spreading dynamics on temporal networks. However, PT implicitly assumes
that edges and nodes are continuously active during the network sampling period -
an assumption that does not always hold in real networks. We systematically
analyze a recently-proposed restriction of PT that preserves node lifetimes
(PTN), and a similar restriction (PTE) that also preserves edge lifetimes. We use
PT, PTN, and PTE to characterize spreading dynamics on (i) synthetic networks
with heterogeneous edge lifespans and tunable burstiness, and (ii) four real
world networks, including two in which nodes enter and leave the network
dynamically. We find that predictions of spreading speed can change considerably
with the choice of reference model. Moreover, the degree of disparity in the
predictions reflects the extent of node/edge turnover, highlighting the
importance of using lifetime-preserving reference models when nodes or edges are
not continuously present in the network.
PMID- 29335423
TI - Evaluation of the effects of space allowance on measures of animal welfare in
laboratory mice.
AB - We studied how space allowance affects measures of animal welfare in mice by
systematically varying group size and cage type across three levels each in both
males and females of two strains of mice (C57BL/6ByJ and BALB/cByJ; n = 216
cages, a total of 1152 mice). This allowed us to disentangle the effects of total
floor area, group size, stocking density, and individual space allocation on a
broad range of measures of welfare, including growth (food and water intake, body
mass); stress physiology (glucocorticoid metabolites in faecal boli);
emotionality (open field behaviour); brain function (recurrent perseveration in a
two-choice guessing task); and home-cage behaviour (activity, stereotypic
behaviour). While increasing group size was associated with a decrease in food
and water intake in general, and more specifically with increased attrition due
to escalated aggression in male BALB mice, no other consistent effects of any
aspect of space allowance were found with respect to the measures studied here.
Our results indicate that within the range of conditions commonly found in
laboratory mouse housing, space allowance as such has little impact on measures
of welfare, except for group size which may be a risk factor for escalating
aggression in males of some strains.
PMID- 29335424
TI - Functionalisation of Detonation Nanodiamond for Monodispersed, Soluble DNA
Nanodiamond Conjugates Using Mixed Silane Bead-Assisted Sonication
Disintegration.
AB - Nanodiamonds have many attractive properties that make them suitable for a range
of biological applications, but their practical use has been limited because
nanodiamond conjugates tend to aggregate in solution during or after
functionalisation. Here we demonstrate the production of DNA-detonation
nanodiamond (DNA-DND) conjugates with high dispersion and solubility using an
ultrasonic, mixed-silanization chemistry protocol based on the in situ Bead
Assisted Sonication Disintegration (BASD) silanization method. We use two silanes
to achieve these properties: (1) 3-(trihydroxysilyl)propyl methylphosphonate
(THPMP); a negatively charged silane that imparts high zeta potential and
solubility in solution; and (2) (3-aminopropyl)triethoxysilane (APTES); a
commonly used functional silane that contributes an amino group for subsequent
bioconjugation. We target these amino groups for covalent conjugation to
thiolated, single-stranded DNA oligomers using the heterobifunctional crosslinker
sulfosuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (Sulfo-SMCC).
The resulting DNA-DND conjugates are the smallest reported to date, as determined
by Dynamic Light Scattering (DLS) and Atomic Force Microscopy (AFM). The
functionalisation method we describe is versatile and can be used to produce a
wide variety of soluble DND-biomolecule conjugates.
PMID- 29335426
TI - Author Correction: Intensification of terrestrial carbon cycle related to El Nino
Southern Oscillation under greenhouse warming.
AB - In the original version of this Article, the affiliation for Su-Jon Jeong was
incorrectly given as 'Southern University of Science and Technology of China
(SUSTECH)', instead of 'Southern University of Science and Technology (SUSTECH)'.
This has now been corrected in both the PDF and HTML versions of the Article.
PMID- 29335425
TI - SPARC expression is associated with hepatic injury in rodents and humans with non
alcoholic fatty liver disease.
AB - Mechanisms that control progression from simple steatosis to steato-hepatitis and
fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) are unknown.
SPARC, a secreted matricellular protein, is over-expressed in the liver under
chronic injury. Contribution of SPARC accumulation to disease severity is largely
unknown in NAFLD. We assessed the hypothesis that SPARC is increased in livers
with more necrosis and inflammation and could be associated with more fibrosis.
qrt-PCR, immunohistochemistry, and ELISA were employed to localize and quantify
changes in SPARC in 62 morbidly obese patients with NAFLD/NASH and in a mouse
model of diet-induced-NASH. Results were correlated with the severity of
NAFLD/NASH. In obese patients 2 subgroups were identified with either high SPARC
expression (n = 16) or low SPARC expression (n = 46) in the liver, with a cutoff
of 1.2 fold expression. High expression of SPARC paralleled hepatocellular damage
and increased mRNA expression of pro-fibrogenic factors in the liver. In line
with these findings, in the NASH animal model SPARC knockout mice were protected
from inflammatory injury, and showed less inflammation and fibrosis. Hepatic
SPARC expression is associated with liver injury and fibrogenic processes in
NAFLD. SPARC has potential as preventive or therapeutic target in NAFLD patients.
PMID- 29335427
TI - Chronic alcohol exposure disrupts top-down control over basal ganglia action
selection to produce habits.
AB - Addiction involves a predominance of habitual control mediated through action
selection processes in dorsal striatum. Research has largely focused on neural
mechanisms mediating a proposed progression from ventral to dorsal lateral
striatal control in addiction. However, over reliance on habit striatal processes
may also arise from reduced cortical input to striatum, thereby disrupting
executive control over action selection. Here, we identify novel mechanisms
through which chronic intermittent ethanol exposure and withdrawal (CIE) disrupts
top-down control over goal-directed action selection processes to produce habits.
We find CIE results in decreased excitability of orbital frontal cortex (OFC)
excitatory circuits supporting goal-directed control, and, strikingly,
selectively reduces OFC output to the direct output pathway in dorsal medial
striatum. Increasing the activity of OFC circuits restores goal-directed control
in CIE-exposed mice. Our findings show habitual control in alcohol dependence can
arise through disrupted communication between top-down, goal-directed processes
onto basal ganglia pathways controlling action selection.
PMID- 29335428
TI - Analysis of the HIV-2 protease's adaptation to various ligands: characterization
of backbone asymmetry using a structural alphabet.
AB - The HIV-2 protease (PR2) is a homodimer of 99 residues with asymmetric assembly
and binding various ligands. We propose an exhaustive study of the local
structural asymmetry between the two monomers of all available PR2 structures
complexed with various inhibitors using a structural alphabet approach. On
average, PR2 exhibits asymmetry in 31% of its positions-i.e., exhibiting
different backbone local conformations in the two monomers. This asymmetry was
observed all along its structure, particularly in the elbow and flap regions. We
first differentiated structural asymmetry conserved in most PR2 structures from
the one specific to some PR2. Then, we explored the origin of the detected
asymmetry in PR2. We localized asymmetry that could be induced by PR2's
flexibility, allowing transition from the semi-open to closed conformations and
the asymmetry potentially induced by ligand binding. This latter could be
important for the PR2's adaptation to diverse ligands. Our results highlighted
some differences between asymmetry of PR2 bound to darunavir and amprenavir that
could explain their differences of affinity. This knowledge is critical for a
better description of PR2's recognition and adaptation to various ligands and for
a better understanding of the resistance of PR2 to most PR2 inhibitors, a major
antiretroviral class.
PMID- 29335429
TI - RFA Guardian: Comprehensive Simulation of Radiofrequency Ablation Treatment of
Liver Tumors.
AB - The RFA Guardian is a comprehensive application for high-performance patient
specific simulation of radiofrequency ablation of liver tumors. We address a wide
range of usage scenarios. These include pre-interventional planning, sampling of
the parameter space for uncertainty estimation, treatment evaluation and, in the
worst case, failure analysis. The RFA Guardian is the first of its kind that
exhibits sufficient performance for simulating treatment outcomes during the
intervention. We achieve this by combining a large number of high-performance
image processing, biomechanical simulation and visualization techniques into a
generalized technical workflow. Further, we wrap the feature set into a single,
integrated application, which exploits all available resources of standard
consumer hardware, including massively parallel computing on graphics processing
units. This allows us to predict or reproduce treatment outcomes on a single
personal computer with high computational performance and high accuracy. The
resulting low demand for infrastructure enables easy and cost-efficient
integration into the clinical routine. We present a number of evaluation cases
from the clinical practice where users performed the whole technical workflow
from patient-specific modeling to final validation and highlight the
opportunities arising from our fast, accurate prediction techniques.
PMID- 29335430
TI - Transspinal Direct Current Stimulation Produces Persistent Plasticity in Human
Motor Pathways.
AB - The spinal cord is an integration center for descending, ascending, and segmental
neural signals. Noninvasive transspinal stimulation may thus constitute an
effective method for concomitant modulation of local and distal neural circuits.
In this study, we established changes in cortical excitability and input/output
function of corticospinal and spinal neural circuits before, at 0-15 and at 30-45
minutes after cathodal, anodal, and sham transspinal direct current stimulation
(tsDCS) to the thoracic region in healthy individuals. We found that
intracortical inhibition was different among stimulation polarities, however
remained unchanged over time. Intracortical facilitation increased after cathodal
and anodal tsDCS delivered with subjects seated, and decreased after cathodal
tsDCS delivered with subjects lying supine. Both cathodal and anodal tsDCS
increased corticospinal excitability, yet facilitation was larger and persisted
for 30 minutes post stimulation only when cathodal tsDCS was delivered with
subjects lying supine. Spinal input/output reflex function was decreased by
cathodal and not anodal tsDCS. These changes may be attributed to altered
spontaneous neural activity and membrane potentials of corticomotoneuronal cells
by tsDCS involving similar mechanisms to those mediating motor learning. Our
findings indicate that thoracic tsDCS has the ability to concomitantly alter
cortical, corticospinal, and spinal motor output in humans.
PMID- 29335431
TI - Synaptic localisation of SRF coactivators, MKL1 and MKL2, and their role in
dendritic spine morphology.
AB - The megakaryoblastic leukaemia (MKL) family are serum response factor (SRF)
coactivators, which are highly expressed in the brain. Accordingly, MKL plays
important roles in dendritic morphology, neuronal migration, and brain
development. Further, nucleotide substitutions in the MKL1 and MKL2 genes are
found in patients with schizophrenia and autism spectrum disorder, respectively.
Thus, studies on the precise synaptic localisation and function of MKL in neurons
are warranted. In this study, we generated and tested new antibodies that
specifically recognise endogenously expressed MKL1 and MKL2 proteins in neurons.
Using these reagents, we biochemically and immunocytochemically show that MKL1
and MKL2 are localised at synapses. Furthermore, shRNA experiments revealed that
postsynaptic deletion of MKL1 or MKL2 reduced the percentage of mushroom- or
stubby-type spines in cultured neurons. Taken together, our findings suggest that
MKL1 and MKL2 are present at synapses and involved in dendritic spine maturation.
This study may, at least in part, contribute to better understanding of the
molecular mechanisms underlying MKL-mediated synaptic plasticity and neurological
disorders.
PMID- 29335432
TI - The relationship of dietary fish intake to diabetic retinopathy and retinal
vascular caliber in patients with type 2 diabetes.
AB - In this cross-sectional study, we evaluated the association of dietary fish
intake with varying severity of diabetic retinopathy (DR) and retinal vascular
caliber in Asians with type 2 diabetes mellitus. 357 Asians (median age: 58
years; 31% women; 78% Chinese) were recruited from a tertiary eye care
institution in Singapore. Fish consumption was evaluated using a validated food
frequency questionnaire. Digital retinal photographs assessed for DR severity and
retinal vascular caliber. Ordered logistic and linear regression models were used
to investigate the association of fish intake with DR severity and vascular
caliber. Increasing frequency of fish consumption was significantly associated
with lower odds of having severe DR (odds ratio [OR] = 0.91, 95% CI: 0.84-0.99
per 1-unit increase of fish intake; P = 0.038). Among those with no retinopathy,
persons in quartile 4 fish intake had a wider retinal vascular caliber for
arteriolar (beta = 22.27 um, 95% CI: 12.64-31.90; P-trend < 0.001) and venular
(beta = 32.00 um, 95% CI: 17.56-46.43; P-trend < 0.001), than those in quartile 1
fish intake. Persons with higher fish intake had a decreased likelihood of having
severe DR. In diabetics without retinopathy, higher fish intake was associated
with wider retinal vascular caliber. Future research is needed to reinforce the
direction of the casualty.
PMID- 29335433
TI - Conformational Landscape of the PRKACA-DNAJB1 Chimeric Kinase, the Driver for
Fibrolamellar Hepatocellular Carcinoma.
AB - In fibrolamellar hepatocellular carcinoma a single genetic deletion results in
the fusion of the first exon of the heat shock protein 40, DNAJB1, which encodes
the J domain, with exons 2-10 of the catalytic subunit of protein kinase A,
PRKACA. This produces an enzymatically active chimeric protein J-PKAcalpha. We
used molecular dynamics simulations and NMR to analyze the conformational
landscape of native and chimeric kinase, and found an ensemble of conformations.
These ranged from having the J-domain tucked under the large lobe of the kinase,
similar to what was reported in the crystal structure, to others where the J
domain was dislodged from the core of the kinase and swinging free in solution.
These simulated dislodged states were experimentally captured by NMR. Modeling of
the different conformations revealed no obvious steric interactions of the J
domain with the rest of the RIIbeta holoenzyme.
PMID- 29335434
TI - Competitive influence maximization and enhancement of synchronization in
populations of non-identical Kuramoto oscillators.
AB - Many networked systems have evolved to optimize performance of function. Much
literature has considered optimization of networks by central planning, but
investigations of network formation amongst agents connecting to achieve non
aligned goals are comparatively rare. Here we consider the dynamics of
synchronization in populations of coupled non-identical oscillators and analyze
adaptations in which individual nodes attempt to rewire network topology to
optimize node-specific aims. We demonstrate that, even though individual nodes'
goals differ very widely, rewiring rules in which each node attempts to connect
to the rest of the network in such a way as to maximize its influence on the
system can enhance synchronization of the collective. The observed speed-up of
consensus finding in this competitive dynamics might explain enhanced
synchronization in real world systems and shed light on mechanisms for improved
consensus finding in society.
PMID- 29335435
TI - Placental Morphology Is Associated with Maternal Depressive Symptoms during
Pregnancy and Toddler Psychiatric Problems.
AB - Maternal depressive symptoms during pregnancy predict increased psychiatric
problems in children. The underlying biological mechanisms remain unclear. Hence,
we examined whether alterations in the morphology of 88 term placentas were
associated with maternal depressive symptoms during pregnancy and psychiatric
problems in 1.9-3.1-years old (Mean = 2.1 years) toddlers. Maternal depressive
symptoms were rated biweekly during pregnancy with the Center of Epidemiological
Studies Depression Scale (n = 86). Toddler psychiatric problems were mother-rated
with the Child Behavior Checklist (n = 60). We found that higher maternal
depressive symptoms throughout pregnancy [B = -0.24 Standard Deviation (SD)
units: 95% Confidence Interval (CI) = -0.46; -0.03: P = 0.03; Mean difference =
0.66 SDs; 95% CI = -0.08; -1.23: P = 0.03; between those with and without
clinically relevant depressive symptoms] were associated with lower variability
in the placental villous barrier thickness of gamma-smooth muscle actin-negative
villi. This placental morphological change predicted higher total (B = -0.34 SDs:
95% CI = -0.60; -0.07: P = 0.01) and internalizing (B = -0.32 SDs: 95% CI =
0.56; -0.08: P = 0.01) psychiatric problems in toddlers. To conclude, our
findings suggest that both maternal depressive symptoms during pregnancy and
toddler psychiatric problems may be associated with lower variability in the
villous membrane thickness of peripheral villi in term placentas. This lower
heterogeneity may compromise materno-fetal exchange, suggesting a possible role
for altered placental morphology in the fetal programming of mental disorders.
PMID- 29335436
TI - Deregulated PP1alpha phosphatase activity towards MAPK activation is antagonized
by a tumor suppressive failsafe mechanism.
AB - The mitogen-activated protein kinase (MAPK) pathway is frequently aberrantly
activated in advanced cancers, including metastatic prostate cancer (CaP).
However, activating mutations or gene rearrangements among MAPK signaling
components, such as Ras and Raf, are not always observed in cancers with
hyperactivated MAPK. The mechanisms underlying MAPK activation in these cancers
remain largely elusive. Here we discover that genomic amplification of the PPP1CA
gene is highly enriched in metastatic human CaP. We further identify an
S6K/PP1alpha/B-Raf signaling pathway leading to activation of MAPK signaling that
is antagonized by the PML tumor suppressor. Mechanistically, we find that
PP1alpha acts as a B-Raf activating phosphatase and that PML suppresses MAPK
activation by sequestering PP1alpha into PML nuclear bodies, hence repressing S6K
dependent PP1alpha phosphorylation, 14-3-3 binding and cytoplasmic accumulation.
Our findings therefore reveal a PP1alpha/PML molecular network that is
genetically altered in human cancer towards aberrant MAPK activation, with
important therapeutic implications.
PMID- 29335437
TI - Deubiquitinase USP13 dictates MCL1 stability and sensitivity to BH3 mimetic
inhibitors.
AB - MCL1 is a pivot member of the anti-apoptotic BCL-2 family proteins. While a
distinctive feature of MCL1 resides in its efficient ubiquitination and
destruction, the deubiquitinase USP9X has been implicated in the preservation of
MCL1 expression by removing the polyubiquitin chains. Here we perform an unbiased
siRNA screen and identify that the second deubiquitinase, USP13, regulates MCL1
stability in lung and ovarian cancer cells. Mechanistically, USP13 interacts with
and stabilizes MCL1 via deubiquitination. As a result, USP13 depletion using
CRISPR/Cas9 nuclease system inhibits tumor growth in xenografted nude mice. We
further report that genetic or pharmacological inhibition of USP13 considerably
reduces MCL1 protein abundance and significantly increases tumor cell sensitivity
to BH3 mimetic inhibitors targeting BCL-2 and BCL-XL. Collectively, we nominate
USP13 as a novel deubiquitinase which regulates MCL1 turnover in diverse solid
tumors and propose that USP13 may be a potential therapeutic target for the
treatment of various malignancies.
PMID- 29335439
TI - Net global warming potential and greenhouse gas intensity as affected by
different water management strategies in Chinese double rice-cropping systems.
AB - This study provides a complete account of global warming potential (GWP) and
greenhouse gas intensity (GHGI) in relation to a long-term water management
experiment in Chinese double-rice cropping systems. The three strategies of water
management comprised continuous (year-round) flooding (CF), flooding during the
rice season but with drainage during the midseason and harvest time (F-D-F), and
irrigation only for flooding during transplanting and the tillering stage (F-RF).
The CH4 and N2O fluxes were measured with the static chamber method. Soil organic
carbon (SOC) sequestration rates were estimated based on the changes in the
carbon stocks during 1998-2014. Longer periods of soil flooding led to increased
CH4 emissions, reduced N2O emissions, and enhanced SOC sequestration. The net
GWPs were 22,497, 8,895, and 1,646 kg CO2-equivalent ha-1 yr-1 for the CF, F-D-F,
and F-RF, respectively. The annual rice grain yields were comparable between the
F-D-F and CF, but were reduced significantly (by 13%) in the F-RF. The GHGIs were
2.07, 0.87, and 0.18 kg CO2-equivalent kg-1 grain yr-1 for the CF, F-D-F, and F
RF, respectively. These results suggest that F-D-F could be used to maintain the
grain yields and simultaneously mitigate the climatic impact of double rice
cropping systems.
PMID- 29335440
TI - Co-action equilibrium fails to predict choices in mixed-strategy settings.
AB - Social projection is the tendency to project one's own characteristics onto
others. This phenomenon can potentially explain cooperation in prisoner's dilemma
experiments and other social dilemmas. The social projection hypothesis has
recently been formalized for symmetric games as co-action equilibrium and for
general games as consistent evidential equilibrium. These concepts have been
proposed to predict choice behavior in experimental one-shot games. We test the
predictions of the co-action equilibrium concept in a simple binary minimizer
game experiment. We find no evidence of social projection.
PMID- 29335438
TI - Grey and white matter volumes either in treatment-naive or hormone-treated
transgender women: a voxel-based morphometry study.
AB - Many previous magnetic resonance imaging (MRI) studies have documented sex
differences in brain morphology, but the patterns of sexual brain differences in
transgender women - male sex assigned at birth - with a diagnosis of gender
dysphoria (TW) have been rarely investigated to date. We acquired T1-weighted MRI
data for the following four (n = 80) groups: treatment-naive TW (TNTW), TW
treated with cross-sex hormones for at least one year (TTW), cisgender men, and
cisgender women (cisgender individuals as controls). Differences in whole-brain
and regional white matter volume and grey matter volume (GMV) were assessed using
voxel-based morphometry. We found lower global brain volumes and regional GMVs in
a large portion of the posterior-superior frontal cortex in the cisgender women
group than in the TTW and cisgender men groups. Additionally, both transgender
groups exhibited lower bilateral insular GMVs than the cisgender women group. Our
results highlight differences in the insula in both transgender groups; such
differences may be characteristic of TW. Furthermore, these alterations in the
insula could be related to the neural network of body perception and reflect the
distress that accompanies gender dysphoria.
PMID- 29335441
TI - A Collective Route to Head and Neck Cancer Metastasis.
AB - Distant metastasis (DM) from head and neck cancers (HNC) portends a poor patient
prognosis. Despite its important biological role, little is known about the cells
which seed these DM. Circulating tumour cells (CTCs) represent a transient cancer
cell population, which circulate in HNC patients' peripheral blood and seed at
distant sites. Capture and analysis of CTCs offers insights into tumour
metastasis and can facilitate treatment strategies. Whilst the data on singular
CTCs have shown clinical significance, the role of CTC clusters in metastasis
remains limited. In this pilot study, we assessed 60 treatment naive HNC patients
for CTCs with disease ranging from early to advanced stages, for CTC clusters
utilizing spiral CTC enrichment technology. Single CTCs were isolated in 18/60
30% (Ranging from Stage I-IV), CTC clusters in 15/60-25% (exclusively Stage IV)
with 3/15-20% of CTC clusters also containing leukocytes. The presence of CTC
clusters associated with the development of distant metastatic disease(P =
0.0313). This study demonstrates that CTC clusters are found in locally advanced
patients, and this may be an important prognostic marker. In vivo and in vitro
studies are warranted to determine the role of these CTC clusters, in particular,
whether leukocyte involvement in CTC clusters has clinical relevance.
PMID- 29335442
TI - Nanostructural Differentiation and Toxicity of Amyloid-beta25-35 Aggregates Ensue
from Distinct Secondary Conformation.
AB - Amyloid nanostructures are originated from protein misfolding and aberrant
aggregation, which is associated with the pathogenesis of many types of
degenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD)
and Huntington's disease. The secondary conformation of peptides is of a
fundamental importance for aggregation and toxicity of amyloid peptides. In this
work, Abeta25-35, a fragment of amyloid beta(1-42) (Abeta42), was selected to
investigate the correlation between secondary structures and toxicity of amyloid
fibrils. Furthermore, each aggregation assemblies show different cell membrane
disruption and cytotoxicity. The structural analysis of amyloid aggregates
originated from different secondary structure motifs is helpful to understand the
mechanism of peptides/cell interactions in the pathogenesis of amyloid diseases.
PMID- 29335444
TI - A Geodetic Strain Rate Model for the East African Rift System.
AB - Here we describe the new Sub-Saharan Africa Geodetic Strain Rate Model v.1.0 (SSA
GSRM v.1.0), which provides fundamental constraints on long-term tectonic
deformation in the region and an improved seismic hazards assessment in Sub
Saharan Africa. Sub-Saharan Africa encompasses the East African Rift System, the
active divergent plate boundary between the Nubian and Somalian plates, where
strain is largely accommodated along the boundaries of three subplates. We
develop an improved geodetic strain rate field for sub-Saharan Africa that
incorporates 1) an expanded geodetic velocity field, 2) redefined regions of
deforming zones guided by seismicity distribution, and 3) updated constraints on
block rotations. SSA-GSRM v.1.0 spans longitudes 22 degrees to 55.5 degrees and
latitudes -52 degrees to 20 degrees with 0.25 degrees (longitude) by 0.2
degrees (latitude) spacing. For plates/sub-plates, we assign rigid block
rotations as constraints on the strain rate calculation that is determined by
fitting bicubic Bessel splines to a new geodetic velocity solution for an
interpolated velocity gradient tensor field. We derive strain rates, velocities,
and vorticity rates from the velocity gradient tensor field. A comparison with
the Global Geodetic Strain Rate model v2.1 reveals regions of previously
unresolved spatial heterogeneities in geodetic strain rate distribution, which
indicates zones of elevated seismic risk.
PMID- 29335443
TI - Elucidating the genomic architecture of Asian EGFR-mutant lung adenocarcinoma
through multi-region exome sequencing.
AB - EGFR-mutant lung adenocarcinomas (LUAD) display diverse clinical trajectories and
are characterized by rapid but short-lived responses to EGFR tyrosine kinase
inhibitors (TKIs). Through sequencing of 79 spatially distinct regions from 16
early stage tumors, we show that despite low mutation burdens, EGFR-mutant Asian
LUADs unexpectedly exhibit a complex genomic landscape with frequent and early
whole-genome doubling, aneuploidy, and high clonal diversity. Multiple truncal
alterations, including TP53 mutations and loss of CDKN2A and RB1, converge on
cell cycle dysregulation, with late sector-specific high-amplitude amplifications
and deletions that potentially beget drug resistant clones. We highlight the
association between genomic architecture and clinical phenotypes, such as co
occurring truncal drivers and primary TKI resistance. Through comparative
analysis with published smoking-related LUAD, we postulate that the high intra
tumor heterogeneity observed in Asian EGFR-mutant LUAD may be contributed by an
early dominant driver, genomic instability, and low background mutation rates.
PMID- 29335445
TI - Trophic ecology of glass sponge reefs in the Strait of Georgia, British Columbia.
AB - Sponges link the microbial loop with benthic communities by feeding on bacteria.
Glass sponge reefs on the continental shelf of western Canada have extremely high
grazing rates, consuming seven times more particulate carbon than can be supplied
by vertical flux alone. Unlike many sponges, the reef building species
Aphrocallistes vastus has no microbial symbionts and removes little dissolved
organic carbon. To determine how reef sponges therefore get enough food to
sustain such substantial grazing we measured stable carbon and nitrogen isotope
signatures of water, sediment and sponge tissues. To ensure samples were
temporally associated, we also studied the duration particles were retained in
tissues in controlled feeding studies using microscopic beads and 13C-labeled
bacteria. Although fecal pellets were expelled from sponges within 24 hours of
feeding, intact bacteria were still found in tissues and sponge tissues retained
elevated 13C levels for at least 14 days. These independent lines of evidence
suggest that carbon in reef sponge tissues may reflect food consumed from days to
weeks earlier. Stable isotope analysis suggests that heterotrophic bacteria
ingested by the sponges comes from a confluence of trophic subsidies: from
terrestrial and oceanic sources, and also potentially on sediment-borne bacteria
resuspended by tidal currents.
PMID- 29335446
TI - Experimental quantum simulation of fermion-antifermion scattering via boson
exchange in a trapped ion.
AB - Quantum field theories describe a variety of fundamental phenomena in physics.
However, their study often involves cumbersome numerical simulations. Quantum
simulators, on the other hand, may outperform classical computational capacities
due to their potential scalability. Here we report an experimental realization of
a quantum simulation of fermion-antifermion scattering mediated by bosonic modes,
using a multilevel trapped ion, which is a simplified model of fermion scattering
in both perturbative and non-perturbative quantum electrodynamics. The simulated
model exhibits prototypical features in quantum field theory including particle
pair creation and annihilation, as well as self-energy interactions. These are
experimentally observed by manipulating four internal levels of a 171Yb+ trapped
ion, where we encode the fermionic modes, and two motional degrees of freedom
that simulate the bosonic modes. Our experiment establishes an avenue towards the
efficient implementation of field modes, which may prove useful in studies of
quantum field theories including non-perturbative regimes.
PMID- 29335447
TI - Exposure to famine in early life and chronic kidney diseases in adulthood.
AB - OBJECTIVE: Chronic kidney disease (CKD) is an increasing contributor to the
global disease burden. Previous findings indicated that exposure to famine in
early life was associated with various metabolic diseases and urinary protein
levels. We aimed to assess whether the exposure to China's Great Famine 1959-1962
during fetal or childhood period was associated with glomerular filtration rate
(GFR) and risk of CKD (eGFR<60 mL/min per 1.73 m2) in adulthood. MATERIALS AND
METHODS: SPECT-China was a population-based observational study in 2014-2015.
Totally, 5124 women were included from SPECT-China study. Based on the birth
year, they were divided into fetal-exposed (1959-1962), childhood-exposed (1949
1958), adolescence/young adult-exposed (1921-1948), and non-exposed (1963-1974,
reference). The estimated glomerular filtration rate (eGFR) was calculated
according to the Chronic Kidney Disease Epidemiology Collaboration equation. CKD
was defined as eGFR less than 60 mL/min per 1.73 m2. RESULTS: Compared with the
non-exposed, fetal exposure to famine was significantly associated with lower
eGFR (B -1.47, 95%CI -2.81, -1.13) and greater risk of having CKD (OR 2.85, 95%CI
1.25, 6.50) in the crude model adjusting age. Further adjustments for demographic
variables, body mass index, diabetes, and blood pressure did not qualitatively
change the association (eGFR B -1.35, 95%CI -2.67, -0.04; CKD OR 2.42, 95%CI
1.05, 5.58). This association was not found in childhood-exposed and
adolescence/young adult-exposed individuals. CONCLUSIONS: Prenatal exposure to
famine may have long-term effects on declined GFR and the development of CKD in
humans. thus, fetal stage may be an important time window to prevent CKD in later
life.
PMID- 29335448
TI - Regional evaluation of childhood acute lymphoblastic leukemia genetic
susceptibility loci among Japanese.
AB - Genome-wide association studies (GWAS) performed mostly in populations of
European and Hispanic ancestry have confirmed an inherited genetic basis for
childhood acute lymphoblastic leukemia (ALL), but these associations are less
clear in other races/ethnicities. DNA samples from ALL patients (aged 0-19 years)
previously enrolled onto a Tokyo Children's Cancer Study Group trial were
collected during 2013-2015, and underwent single nucleotide polymorphism (SNP)
microarray genotyping resulting in 527 B-cell ALL for analysis. Cases and control
data for 3,882 samples from the Nagahama Study Group and Aichi Cancer Center
Study were combined, and association analyses across 10 previous GWAS-identified
regions were performed after targeted SNP imputation. Linkage disequilibrium (LD)
patterns in Japanese and other populations were evaluated using the varLD score
based on 1000 Genomes data. Risk associations for ARID5B (rs10821936, OR = 1.84,
P = 6 * 10-17) and PIP4K2A (rs7088318, OR = 0.76, P = 2 * 10-4) directly
transferred to Japanese, and the IKZF1 association was detected by an alternate
SNP (rs1451367, OR = 1.52, P = 2 * 10-6). Marked regional LD differences between
Japanese and Europeans was observed for most of the remaining loci for which
associations did not transfer, including CEBPE, CDKN2A, CDKN2B, and ELK3. This
study represents a first step towards characterizing the role of genetic
susceptibility in childhood ALL risk in Japanese.
PMID- 29335449
TI - Transcriptome profile of NO-induced Arabidopsis transcription factor genes
suggests their putative regulatory role in multiple biological processes.
AB - TFs are important proteins regulating plant responses during environmental
stresses. These insults typically induce changes in cellular redox tone driven in
part by promoting the production of reactive nitrogen species (RNS). The main
source of these RNS is nitric oxide (NO), which serves as a signalling molecule,
eliciting defence and resistance responses. To understand how these signalling
molecules regulate key biological processes, we performed a large scale S
nitrosocysteine (CySNO)-mediated RNA-seq analysis. The DEGs were analysed to
identify potential regulatory TFs. We found a total of 673 (up- and down
regulated) TFs representing a broad range of TF families. GO-enrichment and
MapMan analysis suggests that more than 98% of TFs were mapped to the Arabidopsis
thaliana genome and classified into pathways like hormone signalling, protein
degradation, development, biotic and abiotic stress, etc. A functional analysis
of three randomly selected TFs, DDF1, RAP2.6, and AtMYB48 identified a regulatory
role in plant growth and immunity. Loss-of-function mutations within DDF1 and
RAP2.6 showed compromised basal defence and effector triggered immunity,
suggesting their positive role in two major plant defence systems. Together,
these results imply an important data representing NO-responsive TFs that will
help in exploring the core mechanisms involved in biological processes in plants.
PMID- 29335452
TI - Chaotic universe model.
AB - In this study, we consider nonlinear interactions between components such as dark
energy, dark matter, matter and radiation in the framework of the Friedman
Robertson-Walker space-time and propose a simple interaction model based on the
time evolution of the densities of these components. By using this model we show
that these interactions can be given by Lotka-Volterra type equations. We
numerically solve these coupling equations and show that interaction dynamics
between dark energy-dark matter-matter or dark energy-dark matter-matter
radiation has a strange attractor for 0 > w de >-1, w dm >= 0, w m >= 0 and w
r >= 0 values. These strange attractors with the positive Lyapunov exponent
clearly show that chaotic dynamics appears in the time evolution of the
densities. These results provide that the time evolution of the universe is
chaotic. The present model may have potential to solve some of the cosmological
problems such as the singularity, cosmic coincidence, big crunch, big rip,
horizon, oscillation, the emergence of the galaxies, matter distribution and
large-scale organization of the universe. The model also connects between
dynamics of the competing species in biological systems and dynamics of the time
evolution of the universe and offers a new perspective and a new different
scenario for the universe evolution.
PMID- 29335450
TI - Copper sulfide nanoparticles as a photothermal switch for TRPV1 signaling to
attenuate atherosclerosis.
AB - Atherosclerosis is characterized by the accumulation of lipids within the
arterial wall. Although activation of TRPV1 cation channels by capsaicin may
reduce lipid storage and the formation of atherosclerotic lesions, a clinical use
for capsaicin has been limited by its chronic toxicity. Here we show that
coupling of copper sulfide (CuS) nanoparticles to antibodies targeting TRPV1 act
as a photothermal switch for TRPV1 signaling in vascular smooth muscle cells
(VSMCs) using near-infrared light. Upon irradiation, local increases of
temperature open thermo-sensitive TRPV1 channels and cause Ca2+ influx. The
increase in intracellular Ca2+ activates autophagy and impedes foam cell
formation in VSMCs treated with oxidized low-density lipoprotein. In vivo, CuS
TRPV1 allows photoacoustic imaging of the cardiac vasculature and reduces lipid
storage and plaque formation in ApoE-/- mice fed a high-fat diet, with no obvious
long-term toxicity. Together, this suggests CuS-TRPV1 may represent a therapeutic
tool to locally and temporally attenuate atherosclerosis.
PMID- 29335451
TI - A hot-spot mutation in CDC42 (p.Tyr64Cys) and novel phenotypes in the third
patient with Takenouchi-Kosaki syndrome.
AB - Takenouchi-Kosaki syndrome (TKS) is a congenital malformation syndrome
characterized by severe developmental delay, macrothrombocytopenia,
camptodactyly, sensorineural hearing loss, and dysmorphic facial features.
Recently, a heterozygous de novo mutation (p.Tyr64Cys) in the CDC42 gene, which
encodes a key small GTP-binding protein of the Rho-subfamily, was identified in
two unrelated patients with TKS. We herein report a third patient with TKS who
had the same heterozygous CDC42 mutation. The phenotype of the patient was very
similar to those of the two previously reported patients with TKS; however, she
also demonstrated novel clinical manifestations, such as congenital
hypothyroidism and immunological disturbance. Thus, despite the heterozygous
mutation of CDC42 (p.Tyr64Cys) likely being a hot-spot mutation for TKS, its
phenotype may be variable. Further studies and the accumulation of patients with
CDC42 mutations are needed to clarify the phenotype in patients with TKS and the
pathophysiological roles of the CDC42 mutation.
PMID- 29335453
TI - Engineering Yarrowia lipolytica to Simultaneously Produce Lipase and Single Cell
Protein from Agro-industrial Wastes for Feed.
AB - Lipases are scarcely exploited as feed enzymes in hydrolysis of lipids for
increasing energy supply and improving nutrient use efficiency. In this work, we
performed homologous overexpression, in vitro characterization and in vivo
assessment of a lipase from the yeast Yarrowia lipolytica for feed purpose.
Simultaneously, a large amount of yeast cell biomass was produced, for use as
single cell protein, a potential protein-rich feed resource. Three kinds of low
cost agro-industrial wastes were tested as substrates for simultaneous production
of lipase and single cell protein (SCP) as feed additives: sugarcane molasses,
waste cooking oil and crude glycerol from biodiesel production. Sugarcane
molasses appeared as the most effective cheap medium, allowing production of
16420 U/ml of lipase and 151.2 g/L of single cell protein at 10 liter
fermentation scale. In vitro characterization by mimicking a gastro-intestinal
environment and determination of essential amino acids of the SCP, and in vivo
oral feeding test on fish all revealed that lipase, SCP and their combination
were excellent feed additives. Such simultaneous production of this lipase and
SCP could address two main concerns of feed industry, poor utilization of lipid
and shortage of protein resource at the same time.
PMID- 29335455
TI - Publisher Correction: Trapping and manipulation of nanoparticles using multifocal
optical vortex metalens.
AB - A correction to this article has been published and is linked from the HTML
version of this paper. The error has been fixed in the paper.
PMID- 29335454
TI - Relationship between spectrotemporal modulation detection and music perception in
normal-hearing, hearing-impaired, and cochlear implant listeners.
AB - The objective of this study was to examine the relationship between
spectrotemporal modulation (STM) sensitivity and the ability to perceive music.
Ten normal-nearing (NH) listeners, ten hearing aid (HA) users with moderate
hearing loss, and ten cochlear Implant (CI) users participated in this study.
Three different types of psychoacoustic tests including spectral modulation
detection (SMD), temporal modulation detection (TMD), and STM were administered.
Performances on these psychoacoustic tests were compared to music perception
abilities. In addition, psychoacoustic mechanisms involved in the improvement of
music perception through HA were evaluated. Music perception abilities in unaided
and aided conditions were measured for HA users. After that, HA benefit for music
perception was correlated with aided psychoacoustic performance. STM detection
study showed that a combination of spectral and temporal modulation cues were
more strongly correlated with music perception abilities than spectral or
temporal modulation cues measured separately. No correlation was found between
music perception performance and SMD threshold or TMD threshold in each group.
Also, HA benefits for melody and timbre identification were significantly
correlated with a combination of spectral and temporal envelope cues though HA.
PMID- 29335456
TI - Incidence of solid tumors in polycythemia vera treated with phlebotomy with or
without hydroxyurea: ECLAP follow-up data.
PMID- 29335457
TI - An equation-of-state-meter of quantum chromodynamics transition from deep
learning.
AB - A primordial state of matter consisting of free quarks and gluons that existed in
the early universe a few microseconds after the Big Bang is also expected to form
in high-energy heavy-ion collisions. Determining the equation of state (EoS) of
such a primordial matter is the ultimate goal of high-energy heavy-ion
experiments. Here we use supervised learning with a deep convolutional neural
network to identify the EoS employed in the relativistic hydrodynamic simulations
of heavy ion collisions. High-level correlations of particle spectra in
transverse momentum and azimuthal angle learned by the network act as an
effective EoS-meter in deciphering the nature of the phase transition in quantum
chromodynamics. Such EoS-meter is model-independent and insensitive to other
simulation inputs including the initial conditions for hydrodynamic simulations.
PMID- 29335458
TI - Publisher Correction: Microbial network of the carbonate precipitation process
induced by microbial consortia and the potential application to crack healing in
concrete.
AB - A correction to this article has been published and is linked from the HTML
version of this paper. The error has been fixed in the paper.
PMID- 29335459
TI - Publisher Correction: Discovery of targetable genetic alterations in advanced non
small cell lung cancer using a next-generation sequencing-based circulating tumor
DNA assay.
AB - A correction to this article has been published and is linked from the HTML
version of this paper. The error has been fixed in the paper.
PMID- 29335460
TI - God is watching: history in the age of near-infinite digital archives.
PMID- 29335461
TI - Pixelated spatial gene expression analysis from tissue.
AB - Here, we present a technique that performs on-chip picoliter real-time reverse
transcriptase loop mediated isothermal amplification (RT-LAMP) reactions on a
histological tissue section without any analyte purification while preserving the
native spatial location of the nucleic acid molecules. We demonstrate this method
by amplifying TOP2A messenger RNA (mRNA) in a prostate cancer xenograft with 100
um spatial resolution and by visualizing the variation in threshold time of
amplification across the tissue. The on-chip reaction was validated by mRNA
fluorescence in situ hybridization (mFISH) from cells in the tissue section. The
entire process, from tissue loading on microchip to results from RT-LAMP can be
carried out in less than 2 h. We anticipate that this technique, with its ease of
use, fast turnaround, and quantitative molecular outputs, would become an
invaluable tissue analysis tool for researchers and clinicians in the biomedical
arena.
PMID- 29335462
TI - Iron-related toxicity of single-walled carbon nanotubes and crocidolite fibres in
human mesothelial cells investigated by Synchrotron XRF microscopy.
AB - Carbon nanotubes (CNTs) are promising products in industry and medicine, but
there are several human health concerns since their fibrous structure resembles
asbestos. The presence of transition metals, mainly iron, in the fibres seems
also implicated in the pathogenetic mechanisms. To unravel the role of iron at
mesothelial level, we compared the chemical changes induced in MeT-5A cells by
the exposure to asbestos (crocidolite) or CNTs at different content of iron
impurities (raw-SWCNTs, purified- and highly purified-SWCNTs). We applied
synchrotron-based X-Ray Fluorescence (XRF) microscopy and soft X-ray imaging
(absorption and phase contrast images) to monitor chemical and morphological
changes of the exposed cells. In parallel, we performed a ferritin assay. X-ray
microscopy imaging and XRF well localize the crocidolite fibres interacting with
cells, as well as the damage-related morphological changes. Differently, CNTs
presence could be only partially evinced by low energy XRF through carbon
distribution and sometimes iron co-localisation. Compared to controls, the cells
treated with raw-SWCNTs and crocidolite fibres showed a severe alteration of iron
distribution and content, with concomitant stimulation of ferritin production.
Interestingly, highly purified nanotubes did not altered iron metabolism. The
data provide new insights for possible CNTs effects at mesothelial/pleural level
in humans.
PMID- 29335463
TI - Sub-kb Hi-C in D. melanogaster reveals conserved characteristics of TADs between
insect and mammalian cells.
AB - Topologically associating domains (TADs) are fundamental elements of the
eukaryotic genomic structure. However, recent studies suggest that the insulating
complexes, CTCF/cohesin, present at TAD borders in mammals are absent from those
in Drosophila melanogaster, raising the possibility that border elements are not
conserved among metazoans. Using in situ Hi-C with sub-kb resolution, here we
show that the D. melanogaster genome is almost completely partitioned into >4000
TADs, nearly sevenfold more than previously identified. The overwhelming majority
of these TADs are demarcated by the insulator complexes, BEAF-32/CP190, or BEAF
32/Chromator, indicating that these proteins may play an analogous role in flies
as that of CTCF/cohesin in mammals. Moreover, extended regions previously thought
to be unstructured are shown to consist of small contiguous TADs, a property also
observed in mammals upon re-examination. Altogether, our work demonstrates that
fundamental features associated with the higher-order folding of the genome are
conserved from insects to mammals.
PMID- 29335464
TI - Evaluation of endothelial function by VOP and inflammatory biomarkers in patients
with arterial hypertension.
AB - Hypertension is associated with microcirculatory impairment. Our objectives were
to evaluate endothelial function and inflammatory biomarkers in patients with
resistant (RH) and mild to moderate (MMH) arterial hypertension in comparison to
normotensives (control group-CG). Three groups, 25 patients each, have been
investigated, by anamnesis, venous occlusion plethysmography (VOP) and serum
determination of adhesion molecules (VCAM, ICAM), adiponectin, endothelin and C
reactive protein (CRP). Patients not using statins and with or without blood
pressure control were also analyzed. RH group showed smaller percentage increase
of maximum forearm blood flow (FBF) (endothelial-dependent vasodilatation) than
controls (p < 0.05), but no significant difference could be detected between MMH
and CG groups on maximum FBF and minimum vascular resistance post-ischemia. RH
and MMH groups showed higher resistance averages compared to controls (p < 0.05).
Uncontrolled BP in hypertensive patients showed worse results for blood flow and
resistance. Endothelial-independent vasodilatation was not affected. Endothelin
levels were higher in RH and MMH groups (p < 0.05) not using statins. CRP was
significantly higher only in RH compared to CG (p < 0.05). In conclusion patients
with severe hypertension and lack of blood pressure control showed greater
impairment of endothelial function with higher CRP and endothelin levels.
PMID- 29335465
TI - The high concentration of progesterone is harmful for endometrial receptivity and
decidualization.
AB - Progesterone is required for the establishment and maintenance of mammalian
pregnancy and widely used for conservative treatment of luteal phase deficiency
in clinics. However, there are limited solid evidences available for the optimal
timing and dose of progesterone therapy, especially for the possible adverse
effects on implantation and decidualization when progesterone is administrated
empirically. In our study, mouse models were used to examine effects of excess
progesterone on embryo implantation and decidualization. Our data indicate that
excess progesterone is not only harmful for mouse implantation, but also impairs
mouse decidualization. In excess progesterone-treated mice, the impaired
LIF/STAT3 pathway and dysregulated endoplasmic reticulum stress may lead to the
inhibition of embryo implantation and decidualization. It is possible that the
decrease in birth weight of excess progesterone-treated mice is due to a
compromised embryo implantation and decidualization. Furthermore, excess
progesterone compromises in vitro decidualization of human endometrial stromal
cells.
PMID- 29335466
TI - Deeply-sourced formate fuels sulfate reducers but not methanogens at Lost City
hydrothermal field.
AB - Hydrogen produced during water-rock serpentinization reactions can drive the
synthesis of organic compounds both biotically and abiotically. We investigated
abiotic carbon production and microbial metabolic pathways at the high energy but
low diversity serpentinite-hosted Lost City hydrothermal field. Compound-specific
14C data demonstrates that formate is mantle-derived and abiotic in some
locations and has an additional, seawater-derived component in others. Lipids
produced by the dominant member of the archaeal community, the Lost City
Methanosarcinales, largely lack 14C, but metagenomic evidence suggests they
cannot use formate for methanogenesis. Instead, sulfate-reducing bacteria may be
the primary consumers of formate in Lost City chimneys. Paradoxically, the
archaeal phylotype that numerically dominates the chimney microbial communities
appears ill suited to live in pure hydrothermal fluids without the co-occurrence
of organisms that can liberate CO2. Considering the lack of dissolved inorganic
carbon in such systems, the ability to utilize formate may be a key trait for
survival in pristine serpentinite-hosted environments.
PMID- 29335467
TI - An engineered CARS substrate with giant field enhancement in crisscross dimer
nanostructure.
AB - We theoretically investigate the optical properties of a nanostructure consisting
of the two identical and symmetrically arranged crisscrosses. A plasmonic Fano
resonance is induced by a strong interplay between bright mode and dark modes,
where the bright mode is due to electric dipole resonance while dark modes
originate from the magnetic dipole induced by LC resonances. In this article, we
find that the electric field "hotspots" corresponding to three different
wavelengths can be positioned at the same spatial position, and its spectral
tunability is achieved by changing geometric parameters. The crisscrosses system
can be designed as a plasmonic substrate for enhancing Coherent Anti-Stokes Raman
Scattering (CARS) signal. This discovery provides a new method to achieve single
molecule detection. At the same time, it also has many important applications for
multi-photon imaging and other nonlinear optical processes, such as four-wave
mixing and stimulated Raman scattering.
PMID- 29335468
TI - AICDA drives epigenetic heterogeneity and accelerates germinal center-derived
lymphomagenesis.
AB - Epigenetic heterogeneity is emerging as a feature of tumors. In diffuse large B
cell lymphoma (DLBCL), increased cytosine methylation heterogeneity is associated
with poor clinical outcome, yet the underlying mechanisms remain unclear.
Activation-induced cytidine deaminase (AICDA), an enzyme that mediates affinity
maturation and facilitates DNA demethylation in germinal center (GC) B cells, is
required for DLBCL pathogenesis and linked to inferior outcome. Here we show that
AICDA overexpression causes more aggressive disease in BCL2-driven murine
lymphomas. This phenotype is associated with increased cytosine methylation
heterogeneity, but not with increased AICDA-mediated somatic mutation burden.
Reciprocally, the cytosine methylation heterogeneity characteristic of normal GC
B cells is lost upon AICDA depletion. These observations are relevant to human
patients, since DLBCLs with high AICDA expression manifest increased methylation
heterogeneity vs. AICDA-low DLBCLs. Our results identify AICDA as a driver of
epigenetic heterogeneity in B-cell lymphomas with potential significance for
other tumors with aberrant expression of cytidine deaminases.
PMID- 29335469
TI - Structural basis for chitin acquisition by marine Vibrio species.
AB - Chitin, an insoluble polymer of N-acetylglucosamine, is one of the most abundant
biopolymers on Earth. By degrading chitin, chitinolytic bacteria such as Vibrio
harveyi are critical for chitin recycling and maintenance of carbon and nitrogen
cycles in the world's oceans. A decisive step in chitin degradation is the uptake
of chito-oligosaccharides by an outer membrane protein channel named chitoporin
(ChiP). Here, we report X-ray crystal structures of ChiP from V. harveyi in the
presence and absence of chito-oligosaccharides. Structures without bound sugar
reveal a trimeric assembly with an unprecedented closing of the transport pore by
the N-terminus of a neighboring subunit. Substrate binding ejects the pore plug
to open the transport channel. Together with molecular dynamics simulations,
electrophysiology and in vitro transport assays our data provide an explanation
for the exceptional affinity of ChiP for chito-oligosaccharides and point to an
important role of the N-terminal gate in substrate transport.
PMID- 29335470
TI - Stratospheric ozone loss over the Eurasian continent induced by the polar vortex
shift.
AB - The Montreal Protocol has succeeded in limiting major ozone-depleting substance
emissions, and consequently stratospheric ozone concentrations are expected to
recover this century. However, there is a large uncertainty in the rate of
regional ozone recovery in the Northern Hemisphere. Here we identify a Eurasia
North America dipole mode in the total column ozone over the Northern Hemisphere,
showing negative and positive total column ozone anomaly centres over Eurasia and
North America, respectively. The positive trend of this mode explains an enhanced
total column ozone decline over the Eurasian continent in the past three decades,
which is closely related to the polar vortex shift towards Eurasia. Multiple
chemistry-climate-model simulations indicate that the positive Eurasia-North
America dipole trend in late winter is likely to continue in the near future. Our
findings suggest that the anticipated ozone recovery in late winter will be
sensitive not only to the ozone-depleting substance decline but also to the polar
vortex changes, and could be substantially delayed in some regions of the
Northern Hemisphere extratropics.
PMID- 29335471
TI - Raman enhancement on ultra-clean graphene quantum dots produced by quasi
equilibrium plasma-enhanced chemical vapor deposition.
AB - Graphene is regarded as a potential surface-enhanced Raman spectroscopy (SERS)
substrate. However, the application of graphene quantum dots (GQDs) has had
limited success due to material quality. Here, we develop a quasi-equilibrium
plasma-enhanced chemical vapor deposition method to produce high-quality ultra
clean GQDs with sizes down to 2 nm directly on SiO2/Si, which are used as SERS
substrates. The enhancement factor, which depends on the GQD size, is higher than
conventional graphene sheets with sensitivity down to 1 * 10-9 mol L-1 rhodamine.
This is attributed to the high-quality GQDs with atomically clean surfaces and
large number of edges, as well as the enhanced charge transfer between molecules
and GQDs with appropriate diameters due to the existence of Van Hove
singularities in the electronic density of states. This work demonstrates a
sensitive SERS substrate, and is valuable for applications of GQDs in graphene
based photonics and optoelectronics.
PMID- 29335472
TI - Provided support, caregiver burden and well-being in partners of persons with
spinal cord injury 5 years after discharge from first inpatient rehabilitation.
AB - STUDY DESIGN: Cross-sectional study. OBJECTIVES: To describe type and regularity
of support given by partners for individuals with paraplegia versus tetraplegia 5
years after discharge from first inpatient rehabilitation; to describe perceived
caregiver burden, mental health and life satisfaction among partners; and to
analyse determinants of perceived burden and the partner's mental health and life
satisfaction. SETTING: The Netherlands. METHODS: Participants were partners of
persons with spinal cord injury (SCI) 5 years after discharge from first
inpatient rehabilitation (N = 67). Participants completed a self-report
questionnaire. Provided support was assessed with an existing scale consisting of
25 activities for which partners could indicate how often they provide support to
the patient. Caregiver burden was assessed with the Caregiver Strain Index.
Mental health was measured with the Short-Form Health Survey 36 (mental health
subscale), and life satisfaction was measured with the Life Satisfaction
Questionnaire. RESULTS: Five years after inpatient rehabilitation, partners
provided support with a large variety of activities. How often and in which
activities partners provided support was associated with lesion level. About 43%
of the partners experienced high levels of caregiver burden. Provided support was
related to perceived burden (rS = 0.58) and life satisfaction (rS = -0.24), and
burden was negatively related to mental health (rS = -0.47) and life satisfaction
(rS = -0.67). CONCLUSIONS: High levels of perceived burden among partners and the
associations between higher burden with lower well-being show the importance to
prevent caregiver overload in partners of individuals with SCI. Monitoring burden
during regular rehabilitation visits may help to early detect burden.
PMID- 29335473
TI - Mental health and life satisfaction of individuals with spinal cord injury and
their partners 5 years after discharge from first inpatient rehabilitation.
AB - STUDY DESIGN: Cross-sectional study. OBJECTIVES: To describe and compare mental
health and life satisfaction between individuals with spinal cord injury (SCI)
and their partners 5 years after discharge from first inpatient rehabilitation;
and to examine if injury severity moderates the association between individuals'
with SCI and their partners' mental health and life satisfaction. SETTING: Dutch
community. METHODS: Sixty-five individuals with SCI and their partners completed
a self-report questionnaire. Main outcome measures were the mental health
subscale of the Short-Form Health Survey and the Life Satisfaction Questionnaire.
RESULTS: Levels of mental health and life satisfaction of individuals with SCI
and partners were similar, with median scores of 76 and 4.8 versus 76 and 4.6,
respectively. Moderate to strong correlations between individuals with SCI and
their partners were found for the mental health (rS = 0.35) and life satisfaction
scores (rS = 0.51). These associations were generally stronger in the subgroup of
individuals with less severe SCI. Associations between scores on separate life
domains ranged from negligible (0.05) to moderate (0.53). Individuals with SCI
and their partners were least satisfied with their 'sexual life'. Compared with
their partners, individuals with SCI were significantly more satisfied in the
domains 'leisure situation', 'partnership relation' and 'family life', and less
satisfied in 'self-care ability'. CONCLUSIONS: This study showed similarities but
also differences in mental health and life satisfaction between individuals with
SCI and their partners. In clinical practice, attention on mental health and life
satisfaction should, therefore, focus on different domains for individuals with
SCI and partners.
PMID- 29335474
TI - Low vitamin D levels are independent predictors of 1-year worsening in physical
function in people with chronic spinal cord injury: a longitudinal study.
AB - STUDY DESIGN: Longitudinal cohort study. OBJECTIVE: To explore the longitudinal
association of baseline vitamin D levels with 1-year change in physical function
outcomes in people with chronic spinal cord injury (SCI). SETTING: Rehabilitation
institute. METHODS: Sixty-seven patients (44 men and 23 women) with chronic SCI
admitted to a rehabilitation program were included. Functional independence in
daily living activities (as evaluated by the Spinal Cord Independence Measure
version III, SCIM III) and leisure time physical activity (LTPA) were assessed as
measures of physical function at the admission and re-assessed 1-year later.
Comorbidity was scored by Charlson comorbidity index (CCI). RESULTS: A 1-year
worsening in SCIM and LTPA were registered in 44 and 40 patients (66% and 60% of
the study population), respectively. They exhibited significantly lower baseline
25(OH)D levels, higher CCI, and shorter distance from the injury. At the multiple
linear regression analyses, lower baseline 25(OH)D levels exhibited a significant
independent association with higher percentages of 1-year worsening in both SCIM
and LTPA. At ROC analysis, baseline 25(OH)D levels <18.6 and <18.2 ng/mL
discriminated individuals with 1-year worsening in SCIM and LTPA, respectively.
According to these cut-off points, at the multiple logistic regression analysis,
patients with low baseline 25(OH)D levels exhibited an OR of worsening in SCIM
and LTPA engagement 2.8- and 2.6-fold higher, after adjustment for CCI, distance
from injury, and post-follow-up 25(OH)D levels. CONCLUSIONS: In people with
chronic SCI, a low 25(OH)D level may represent an independent predictor of
worsening in physical function outcomes over time.
PMID- 29335475
TI - Discontinuous ventilator weaning of patients with acute SCI.
AB - STUDY DESIGN: Retrospective, single centre cohort study. OBJECTIVES: To determine
factors associated with ventilator weaning success and failure in patients with
acute spinal cord injury (SCI); determine length of time and attempts required to
wean from the ventilator successfully and determine the incidence of pneumonia.
SETTING: BG Klinikum Hamburg, Level 1 trauma centre, SCI Department, Germany.
METHODS: From 2010 until 2017, 165 consecutive patients with cervical SCI,
initially dependent on a ventilator, were included and weaned discontinuously via
tracheal cannula. Data related to anthropometric details, neurological injury,
respiratory outcomes, and weaning parameters were prospectively recorded in a
database and retrospectively analysed. RESULTS: Seventy-nine percent of all
patients were successfully weaned from ventilation. Average duration of the
complete weaning process was 37 days. Ninety-one percent of the successfully
weaned patients completed this on first attempt. Age (>56 years), level of injury
(C4 and/or above), vital capacity (<1500 ml), obesity (>25 kg/m2), and chronic
obstructive pulmonary disease (COPD) significantly decreased the chance of
successful weaning. These factors also correlated with a higher number of weaning
attempts. High level of injury, older age, and reduced vital capacity also
increased the duration of the weaning process. Patients with low vital capacity
and concurrent therapy with Baclofen and Dantrolene showed higher rates of
pneumonia. CONCLUSIONS: We conclude that mentioned factors are associated with
weaning outcome and useful for clinical recommendations and patient counselling.
These data further support the complexity of ventilator weaning in the SCI
population due to associated complications, therefore we recommend conducting
weaning of patients with SCI on intensive or intermediate care units (ICU/IMCU)
in specialised centres.
PMID- 29335476
TI - Reliability and validity of the Persian version of the spinal cord injury
lifestyle scale and the health behavior questionnaire in persons with spinal cord
injury.
AB - STUDY DESIGN: Cross-sectional psychometric study. OBJECTIVE: To evaluate the
reliability and validity of a spinal cord injury lifestyle scale (SCILS) and
Health Behavior Questionnaire (HBQ) in the Persian language for persons with
spinal cord injury (SCI). SETTING: Participants were selected among those
referred to health centers and the Brain and Spinal Cord Injury Research Center.
METHOD: In accordance with standard procedure for translation, two
questionnaires, the SCILS and HBQ, were translated using a forward and backward
translation approach by professional translators. Face validity of the
questionnaires was assessed by ten persons with SCI and content validity was
agreed upon by 12 professors from health care teaching universities. To test the
final versions of both questionnaires, 97 persons with SCI were included using a
consecutive sampling method. Other questionnaires were used to assess concurrent
validity (secondary impairment checklist, as well as SCILS and HBQ) and
convergent validity (impact of event scale revised, brief symptom inventory, beck
depression inventory, and functional independence measure). RESULTS: Internal
consistency of SCILS and HBQ, assessed by Cronbach's alpha, was 0.75 for SCILS
and 0.85 for HBQ. Test-retest reliability intraclass correlations were 0.86 and
0.92 for SCILS and HBQ, respectively. The number of current secondary impairments
had a significant and negative correlation with SCILS (r = -0.22, P < 0.001), but
it was not correlated with HBQ. SCILS had a significant and strong correlation
with HBQ (r = 0.65, P < 0.001). CONCLUSION: SCILS and HBQ can be used for
measuring the health behavior of persons with SCI in Iran.
PMID- 29335478
TI - Publisher Correction: Marked bias towards spontaneous synaptic inhibition
distinguishes non-adapting from adapting layer 5 pyramidal neurons in the barrel
cortex.
AB - A correction to this article has been published and is linked from the HTML
version of this paper. The error has been fixed in the paper.
PMID- 29335477
TI - Transcriptomic signatures of cellular and humoral immune responses in older
adults after seasonal influenza vaccination identified by data-driven clustering.
AB - PBMC transcriptomes after influenza vaccination contain valuable information
about factors affecting vaccine responses. However, distilling meaningful
knowledge out of these complex datasets is often difficult and requires advanced
data mining algorithms. We investigated the use of the data-driven Weighted Gene
Correlation Network Analysis (WGCNA) gene clustering method to identify vaccine
response-related genes in PBMC transcriptomic datasets collected from 138 healthy
older adults (ages 50-74) before and after 2010-2011 seasonal trivalent influenza
vaccination. WGCNA separated the 14,197 gene dataset into 15 gene clusters based
on observed gene expression patterns across subjects. Eight clusters were
strongly enriched for genes involved in specific immune cell types and processes,
including B cells, T cells, monocytes, platelets, NK cells, cytotoxic T cells,
and antiviral signaling. Examination of gene cluster membership identified
signatures of cellular and humoral responses to seasonal influenza vaccination,
as well as pre-existing cellular immunity. The results of this study illustrate
the utility of this publically available analysis methodology and highlight genes
previously associated with influenza vaccine responses (e.g., CAMK4, CD19), genes
with functions not previously identified in vaccine responses (e.g., SPON2, MATK,
CST7), and previously uncharacterized genes (e.g. CORO1C, C8orf83) likely related
to influenza vaccine-induced immunity due to their expression patterns.
PMID- 29335479
TI - LPS-induced Vitamin D Receptor Decrease in Oral Keratinocytes Is Associated With
Oral Lichen Planus.
AB - The suppressive function of vitamin D on oral lichen planus (OLP) have been
documented previously. Vitamin D receptor (VDR) expression is down-regulated in
OLP, but the molecular mechanism of its decrease and the related anti
inflammatory contributor of epithelial VDR signaling is unclear. Herein, we
demonstrated that lipopolysaccharide (LPS) remarkedly down-regulated VDR
expression of keratinocytes, and the reduced regulation was dependent on tumor
necrosis factor alpha (TNFalpha)-miR-346 pathway. In human specimen studies, VDR
levels of oral mucosal epithelia from OLP patients decreased substantially
accompanied with robust TNFalpha and miR-346 induction, compared to the normal
tissues. In addition, vitamin D/VDR signaling inhibited LPS-induced p53
upregulated modulator of apoptosis (PUMA) induction in keratinocytes via impeding
nuclear factor-kappaB (NF-kappaB) activation, resulting in keratinocytes
apoptosis reduction. Importantly, PUMA activity was up-regulated strongly in
diseased epithelium, reversely correlated with VDR expression. Totally, our data
indicate that LPS is responsible for VDR downregulation in oral keratinocytes,
which is associated with OLP development.
PMID- 29335482
TI - Engineered nonlinear materials using gold nanoantenna array.
AB - Gold dipole nanoantennas embedded in an organic molecular film provide strong
local electromagnetic fields to enhance both the nonlinear refractive index (n2)
and two-photon absorption (2PA) of the molecules. An enhancement of 53* for 2PA
and 140* for nonlinear refraction is observed for BDPAS (4,4'
bis(diphenylamino)stilbene) at 600 nm with only 3.7% of gold volume fraction. The
complex value of the third-order susceptibility enhancement results in a sign
change of n2 for the effective composite material relative to the pure BDPAS
film. This complex nature of the enhancement and the tunability of the
nanoantenna resonance allow for engineering the effective nonlinear response of
the composite film.
PMID- 29335481
TI - Bioimpedimetric analysis in conjunction with growth dynamics to differentiate
aggressiveness of cancer cells.
AB - Determination of cancer aggressiveness is mainly assessed in tissues by looking
at the grade of cancer. There is a lack of specific method to determine
aggressiveness of cancer cells in vitro. In our present work, we have proposed a
bio-impedance based non-invasive method to differentiate aggressive property of
two breast cancer cell lines. Real-time impedance analysis of MCF-7 (less
aggressive) and MDA-MB-231 cells (more aggressive) demonstrated unique growth
pattern. Detailed slope-analysis of impedance curves at different growth phases
showed that MDA-MB-231 had higher proliferation rate and intrinsic resistance to
cell death, when allowed to grow in nutrient and space limiting conditions. This
intrinsic nature of death resistance of MDA-MB-231 was due to modulation and
elongation of filopodia, which was also observed during scanning electron
microscopy. Results were also similar when validated by cell cycle analysis.
Additionally, wavelet based analysis was used to demonstrate that MCF-7 had
lesser micromotion based cellular activity, when compared with MDA-MB-231.
Combined together, we hypothesize that analysis of growth rate, death resistance
and cellular energy, through bioimpedance based analysis can be used to determine
and compare aggressiveness of multiple cancer cell lines. This further opens
avenues for extrapolation of present work to human tumor tissue samples.
PMID- 29335480
TI - Novel analgesic effects of melanin-concentrating hormone on persistent
neuropathic and inflammatory pain in mice.
AB - The melanin-concentrating hormone (MCH) is a peptidergic neuromodulator
synthesized by neurons in the lateral hypothalamus and zona incerta. MCHergic
neurons project throughout the central nervous system, indicating the
involvements of many physiological functions, but the role in pain has yet to be
determined. In this study, we found that pMCH-/- mice showed lower baseline pain
thresholds to mechanical and thermal stimuli than did pMCH+/+ mice, and the time
to reach the maximum hyperalgesic response was also significantly earlier in both
inflammatory and neuropathic pain. To examine its pharmacological properties, MCH
was administered intranasally into mice, and results indicated that MCH treatment
significantly increased mechanical and thermal pain thresholds in both pain
models. Antagonist challenges with naltrexone (opioid receptor antagonist) and
AM251 (cannabinoid 1 receptor antagonist) reversed the analgesic effects of MCH
in both pain models, suggesting the involvement of opioid and cannabinoid
systems. MCH treatment also increased the expression and activation of CB1R in
the medial prefrontal cortex and dorsolateral- and ventrolateral periaqueductal
grey. The MCH1R antagonist abolished the effects induced by MCH. This is the
first study to suggest novel analgesic actions of MCH, which holds great promise
for the application of MCH in the therapy of pain-related diseases.
PMID- 29335483
TI - Pilot study to assess visualization and therapy of inflammatory mechanisms after
vessel reopening in a mouse stroke model.
AB - After reperfusion therapy in stroke patients secondary inflammatory processes may
increase cerebral damage. In this pilot study, effects of anti-inflammatory
therapy were assessed in a middle cerebral artery occlusion (MCAO) mouse model
after reperfusion. 1 hour after MCAO, the artery was reopened and tacrolimus or
NaCl were administered intra-arterially. Perfusion-weighted (PWI) and diffusion
weighted images (DWI) were obtained by MRI during MCAO. DWI, T2- and T1-weighted
images with and without Bis-5HT-DTPA administration were obtained 24 hours after
MCAO. Neutrophils, Myeloperoxidase-positive-(MPO+)-cells and microglia, including
M1 and M2 phenotypes, were assessed immunohistochemically. Treatment with
tacrolimus led to significantly smaller apparent diffusion coefficient (ADC)
lesion volume within 24 hours (median -55.6mm3, range -81.3 to -3.6, vs. median
8.0 mm3, range 1.2 to 41.0; P = 0.008) and significantly lower enhancement of Bis
5-HT-DTPA (median signal intensity (SI) ratiocortex, median 92.0%, range 82.8% to
97.1%, vs. median 103.1%, range 98.7% to 104.6%; P = 0.008) compared to the NaCl
group. Immunohistochemical analysis showed no significant differences between
both groups. Intra-arterially administered anti-inflammatory agents after
mechanical thrombectomy may improve treatment efficiency in stroke by reducing
infarct volume size and MPO activity.
PMID- 29335484
TI - Microbial Competition of Rhodotorula mucilaginosa UANL-001L and E. coli increase
biosynthesis of Non-Toxic Exopolysaccharide with Applications as a Wide-Spectrum
Antimicrobial.
AB - Bacterial species are able to colonize and establish communities in biotic and
abiotic surfaces. Moreover, within the past five decades, incidence of bacterial
strains resistant to currently used antibiotics has increased dramatically. This
has led to diverse health issues and economical losses for different industries.
Therefore, there is a latent need to develop new and more efficient
antimicrobials. This work reports an increased production of an exopolysaccharide
in a native yeast strain isolated from the Mexican Northeast, Rhodotorula
mucilaginosa UANL-001L, when co-cultured with E. coli. The exopolysaccharide
produced is chemically and physically characterized and its applications as an
antimicrobial and antibiofilm are explored. The exopolysaccharide is capable of
inhibiting planktonic growth and biofilm formation in Escherichia coli,
Pseudomonas aeruginosa and Staphylococcus aureus. Additionally, the
exopolysaccharide studied here does not exhibit cytotoxic effects when assessed
both, in vitro against an H9c2 mammalian cell line, and in vivo in a murine
toxicity model. Taken together, the properties of this exopolysaccharide indicate
that it has potential applications to inhibit bacterial colonization in medical
and industrial settlings.
PMID- 29335485
TI - Electron beam melting in the fabrication of three-dimensional mesh titanium
mandibular prosthesis scaffold.
AB - The study was designed to fulfill effective work-flow to fabricate three
dimensional mesh titanium scaffold for mandibular reconstruction. The 3D titanium
mesh scaffold was designed based on a volunteer with whole mandible defect. (1)
acquisition of the CT data; (2) design with computer aided design (CAD) and
finite element analysis (FEA). The pore size and intervals with the best mechanic
strength was also calculated using FEA. (3) fabrication of the scaffold using
electron beam melting (EBM); (4) implantation surgery. The case recovered well,
without loosening and rejection. Additionally, 12 mandibular defect model beagles
were used to verify the results. The model was established via tooth extraction
and mandibular resection surgeries, and the scaffold was designed individually
based on CT data obtained at 2 weeks after extraction operation. Then scaffolds
were fabricated using 3D EBM, and the implantation surgery was performed at 2
months after extraction operation. All the animals healed well after
implantation, and the grafted mandibular recovered well with time. The relevant
parameters of the grafted mandibular were nearly to the native mandibular at
postoperative 12 months. It is feasible to fabricate mesh titanium scaffold for
repairing mandibular defects individually using reverse engineering, CAD and EBM
techniques.
PMID- 29335486
TI - High-resolution TADs reveal DNA sequences underlying genome organization in
flies.
AB - Despite an abundance of new studies about topologically associating domains
(TADs), the role of genetic information in TAD formation is still not fully
understood. Here we use our software, HiCExplorer (hicexplorer.readthedocs.io) to
annotate >2800 high-resolution (570 bp) TAD boundaries in Drosophila
melanogaster. We identify eight DNA motifs enriched at boundaries, including a
motif bound by the M1BP protein, and two new boundary motifs. In contrast to
mammals, the CTCF motif is only enriched on a small fraction of boundaries
flanking inactive chromatin while most active boundaries contain the motifs bound
by the M1BP or Beaf-32 proteins. We demonstrate that boundaries can be accurately
predicted using only the motif sequences at open chromatin sites. We propose that
DNA sequence guides the genome architecture by allocation of boundary proteins in
the genome. Finally, we present an interactive online database to access and
explore the spatial organization of fly, mouse and human genomes, available at
http://chorogenome.ie-freiburg.mpg.de .
PMID- 29335487
TI - Increased Expression of GLP-1R in Proliferating Islets of Men1 Mice is Detectable
by [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 /PET.
AB - Multiple endocrine neoplasia type 1 (MEN1) is an endocrine tumor syndrome caused
by heterozygous mutations in the MEN1 tumor suppressor gene. The MEN1 pancreas of
the adolescent gene carrier frequently contain diffusely spread pre-neoplasias
and microadenomas, progressing to macroscopic and potentially malignant
pancreatic neuroendocrine tumors (P-NET), which represents the major death cause
in MEN1. The unveiling of the molecular mechanism of P-NET which is not currently
understood fully to allow the optimization of diagnostics and treatment. Glucagon
like peptide 1 (GLP-1) pathway is essential in islet regeneration, i.e.
inhibition of beta-cell apoptosis and enhancement of beta-cell proliferation, yet
involvement of GLP-1 in MEN1 related P-NET has not yet been demonstrated. The
objective of this work was to investigate if normal sized islets of Men1
heterozygous mice have increased Glucagon-like peptide-1 receptor (GLP-1R)
expression compared to wild type islets, and if this increase is detectable in
vivo with positron emission tomography (PET) using [68Ga]Ga-DO3A-VS-Cys40-Exendin
4 (68Ga-Exendin-4). 68Ga-Exendin-4 showed potential for early lesion detection in
MEN1 pancreas due to increased GLP1R expression.
PMID- 29335488
TI - Distinct ERP profiles for auditory processing in infants at-risk for autism and
language impairment.
AB - Early identification of autism spectrum disorder (ASD) is crucial for the
formulation of effective intervention programs. Language deficits may be a
hallmark feature of ASD and language delay observed in ASD shows striking
similarities to that observed in children with language impairment (LI). Auditory
processing deficits are seen in both LI and ASD, however, they have not
previously been compared directly using Event-Related Potentials (ERPs) in the
two at-risk populations. This study aims to characterize infants at-risk for ASD
(HR-ASD) at the electrophysiological level and to compare them with infants at
risk for LI (HR-LI) and controls, to find specific markers with predictive value.
At 12-month-old, auditory processing in HR-ASD, HR-LI and controls was
characterized via ERP oddball paradigm. All infants were then evaluated at 20
months, to investigate the associations between auditory processing and
language/ASD-related outcomes. In both HR-ASD and HR-LI, mismatch response
latency was delayed compared to controls, whereas only HR-ASD showed overall
larger P3 amplitude compared to controls. Interestingly, these ERP measures
correlated with later expressive vocabulary and M-CHAT critical items in the
whole sample. These results may support the use of objective measurement of
auditory processing to delineate pathophysiological mechanisms in ASD, as
compared to LI.
PMID- 29335490
TI - Study on regeneration of waste powder activated carbon through pyrolysis and its
adsorption capacity of phosphorus.
AB - The regeneration of WPAC through pyrolysis and its adsorption capacity of
phosphorus were studied. The optimum conditions for WPAC regeneration were 650
degrees C and 2 h which resulted in a recovery of BET surface and total pore
volume with a value of 1161.4 m2/g and 1.2176 m3/g. WPAC had a maximum PO43--P
adsorption capacity of 9.65 mg/g which was 48.93% of PAC, while RWPAC had a
maximum PO43--P adsorption capacity of 15.31 mg/g which was 77.64% of PAC. The
kinetic analysis revealed that Langmuir model could well describe the adsorption
process of PAC, WPAC and RWPAC on PO43--P and the PO43--P adsorption followed the
pseudo-second-order model.
PMID- 29335489
TI - Direct quantum process tomography via measuring sequential weak values of
incompatible observables.
AB - The weak value concept has enabled fundamental studies of quantum measurement
and, recently, found potential applications in quantum and classical metrology.
However, most weak value experiments reported to date do not require quantum
mechanical descriptions, as they only exploit the classical wave nature of the
physical systems. In this work, we demonstrate measurement of the sequential weak
value of two incompatible observables by making use of two-photon quantum
interference so that the results can only be explained quantum physically. We
then demonstrate that the sequential weak value measurement can be used to
perform direct quantum process tomography of a qubit channel. Our work not only
demonstrates the quantum nature of weak values but also presents potential new
applications of weak values in analyzing quantum channels and operations.
PMID- 29335491
TI - Validation and optimization of the Systemic Inflammation-Based modified Glasgow
Prognostic Score in predicting postoperative outcome of inflammatory bowel
disease: preliminary data.
AB - Systemic Inflammation-Based modified Glasgow Prognostic Score (mGPS) was
developed as an objective tool to grade state of inflammation. However, the
association between mGPS and postoperative complications for inflammatory bowel
disease (IBD) patients was still unknown. In our study, 270 IBD patients [Crohn's
disease (CD), n = 186; Ulcerative colitis (UC), n = 84] from January 2013 and
January 2016 who underwent elective bowel resection were retrospectively
analyzed, and, the levels of preoperative C-reactive protein (CRP) and albumin
were included as parameters of mGPS. The incidence of overall postoperative
complications was 44.81% (121/270), including 46.77% (87/186) of CD and 40.48%
(34/84) of UC. According to multivariate analysis, mGPS (CD: OR = 3.47, p =
0.003; UC: OR = 3.28, p = 0.019) was independently associated with an increased
risk of postoperative complications. Patients with a higher mGPS also suffered
longer postoperative stay and increased SSIs (both p < 0.05). Combining mGPS with
neutrophil ratio improved its prognostic value with a better area under the curve
(AUC), using receiver operating characteristic (ROC) method. Then we confirmed
that mGPS was associated with postoperative complications in IBD patients
undergoing elective bowel resection and the addition of neutrophil ratio enhanced
its prognostic value.
PMID- 29335492
TI - Assessing the effectiveness of NICE criteria for stratifying breast cancer risk
in a UK cohort.
AB - Breast cancer risk is a common indication for referral to clinical genetics
services. UK National Institute of Health and Care Excellence (NICE) guidelines
use family history (FH) to stratify by 10-year risk of breast cancer from age 40.
Patients are stratified into population risk (PR, 10-year risk <3%), moderate
(MR, 3-8%) and high risk (HR, >8%). Women at increased risk are offered screening
at or prior to age 40. To assess the clinical effectiveness of current risk
stratification, FH data were obtained for all unaffected women with a FH of
breast cancer aged <50, referred to cancer genetics from 2000-2010. Patients were
risk stratified by NICE criteria, identifying patients who subsequently developed
breast cancer. A total of 1409 women had 15,414 patient years of follow-up.
Thirty invasive breast cancers developed, 13 in MR and 13 in HR women. Kaplan
Meier analysis demonstrated no significant difference in the rate of breast
cancer development between PR and MR women from ages 40 to 49 (Log rank p =
0.431). There was a significant difference between ages 40 and 49 years between
PR and HR women (p = 0.036), but not on exclusion of BRCA mutation carriers (p =
0.136). NICE absolute 10-year risk thresholds between ages 40 and 49 were not met
in any risk group, when risk was estimated using the guidelines (PR = 0.82%, MR =
1.68%, HR = 3.56%). Our data suggest that improved criteria are required for risk
assessment prior to age 50 and screening resources may be best focussed on those
with highly penetrant mutations in cancer risk genes.
PMID- 29335493
TI - Biophysical feedbacks mediate carbonate chemistry in coastal ecosystems across
spatiotemporal gradients.
AB - Ocean acidification (OA) projections are primarily based on open ocean
environments, despite the ecological importance of coastal systems in which
carbonate dynamics are fundamentally different. Using temperate tide pools as a
natural laboratory, we quantified the relative contribution of community
composition, ecosystem metabolism, and physical attributes to spatiotemporal
variability in carbonate chemistry. We found that biological processes were the
primary drivers of local pH conditions. Specifically, non-encrusting producer
dominated systems had the highest and most variable pH environments and the
highest production rates, patterns that were consistent across sites spanning 11
degrees of latitude and encompassing multiple gradients of natural variability.
Furthermore, we demonstrated a biophysical feedback loop in which net community
production increased pH, leading to higher net ecosystem calcification. Extreme
spatiotemporal variability in pH is, thus, both impacting and driven by
biological processes, indicating that shifts in community composition and
ecosystem metabolism are poised to locally buffer or intensify the effects of OA.
PMID- 29335494
TI - Magnetic Chern Insulators in a monolayer of Transition Metal Trichalcogenides.
AB - A monolayer of transition metal trichalcogenides has received a lot of attention
as potential two dimensional magnetic materials. The system has a honeycomb
structure of transition metal ions, where both spin-orbit coupling and electron
correlation effect play an important role. Here, motivated by these transition
metal series with effective doping or mixed valence case, we propose the possible
realization of magnetic Chern insulators at quarter filled honeycomb lattice. We
show that the interplay of intrinsic spin-orbit coupling and electron correlation
opens a wide region of ferromagnetic Chern insulating phases in between metals
and normal insulators. Within the mean field approximation, we present the phase
diagram of a quarter filled Kane-Mele Hubbard model and also discuss the effects
of Rashba spin-orbit coupling and nearest neighbor interactions on it.
PMID- 29335497
TI - Interference induced enhancement of magneto-optical Kerr effect in ultrathin
magnetic films.
AB - We have studied the magneto-optical spectra of ultrathin magnetic films deposited
on Si substrates coated with an oxide layer (SiOx). We find that the Kerr
rotation angle and the ellipticity of ~1 nm thick CoFeB thin films, almost
transparent to visible light, show a strong dependence on the thickness of the
SiOx layer. The Kerr signal from the 1 nm CoFeB thin film can be larger than that
of ~100 nm thick CoFeB films for a given SiOx thickness and light wavelength. The
enhancement of the Kerr signal occurs when optical interference takes place
within the SiOx layer. Interestingly, under such resonance condition, the
measured Kerr signal is in some cases larger than the estimation despite the good
agreement of the measured and calculated reflection amplitude. We infer the
discrepancy originates from interface states that are distinct from the bulk
characteristics. These results show that optical interference effect can be
utilized to study the magneto-optical properties of ultrathin films.
PMID- 29335496
TI - Localization and function of neurosecretory protein GM, a novel small secretory
protein, in the chicken hypothalamus.
AB - Recently, we discovered a novel cDNA encoding the precursor of a small secretory
protein, neurosecretory protein GL (NPGL), in the hypothalamic infundibulum of
chickens. NPGL plays an important role in the regulation of growth and feeding. A
database search indicated that the NPGL gene has a paralogous gene:
neurosecretory protein GM (NPGM), also in chickens. We identified cDNA encoding
the NPGM precursor in chickens. Morphological analysis showed that NPGM
containing cells are specifically localized in the medial mammillary nucleus (MM)
and infundibular nucleus (IN) in the hypothalamus. In addition, we found that
NPGM and NPGL are co-localized, especially in the MM. The expression levels of
NPGM mRNA gradually decreased during post-hatch development, in contrast to those
of NPGL mRNA. Moreover, we investigated the relationship between NPGM and other
known factors. NPGM was found to be produced in histaminergic neurons in the MM.
NPGM and histidine decarboxylase, a histamine-producing enzyme, displayed similar
expression patterns during post-hatch development. Acute intracerebroventricular
injection of NPGM decreased food intake, similar to the effect of histamine. To
our knowledge, this is the first report of the localization and function of NPGM
in the brain of vertebrates. These results will further advance the understanding
mechanisms underlying energy homeostasis.
PMID- 29335495
TI - Dysfunction of CD19+CD24hiCD27+ B regulatory cells in patients with bullous
pemphigoid.
AB - Bullous pemphigoid (BP) is an autoimmune blistering skin disease characterized by
the production of autoantibodies against the hemidesmosomal protein BP180. B
regulatory cells (Bregs) are crucial in maintaining self-tolerance and
suppressing autoantibody production. However, it is still unclear whether the
dysfunctions of Bregs contributes to the autoantibody production in BP patients.
In this study, we found that CD19+CD24hiCD27+ Bregs and IL-10+CD19+ Bregs were
significantly increased in the peripheral blood samples of BP patients compared
with that in healthy controls. Moreover, compared to Bregs from healthy
individuals, we found that Bregs from BP patients fails to suppress the
production of specific anti-BP180 autoantibody when co-cultured with patient
derived PBMCs. Additionally, Bregs from BP patients were defective in suppressing
the CD4+ T cell proliferation and the cytokines expression (including IFN-gamma,
TNF-alpha and IL-4). Notably, we found that patient-derived Bregs produced high
level of TNF-alpha and the TNF inhibitor etanercept could inhibit the
autoantibody production in the culture system in vitro. Our results indicate that
Bregs from BP patient appear phenotypically pro-inflammatory by their cytokine
profile and are defective in immunosuppressive function, which suggest that Bregs
play a pro-inflammatory role rather than a regulatory role in the pathogenesis of
BP.
PMID- 29335498
TI - Stretchable Electrospun PVDF-HFP/Co-ZnO Nanofibers as Piezoelectric
Nanogenerators.
AB - Herein, we investigate the morphology, structure and piezoelectric performances
of neat polyvinylidene fluoride hexafluoropropylene (PVDF-HFP) and PVDF-HFP/Co
ZnO nanofibers, fabricated by electrospinning. An increase in the amount of
crystalline beta-phase of PVDF-HFP has been observed with the increase in Co
doped ZnO nanofiller concentration in the PVDF-HFP matrix. The dielectric
constants of the neat PVDF-HFP and PVDF-HFP/2 wt.% Co-ZnO nanofibers are derived
as 8 and 38 respectively. The flexible nanogenerator manipulated from the polymer
nanocomposite (PVDF-HFP/Co-ZnO) exhibits an output voltage as high as 2.8 V
compared with the neat PVDF-HFP sample (~120 mV). These results indicate that the
investigated nanocomposite is appropriate for fabricating various flexible and
wearable self-powered electrical devices and systems.
PMID- 29335500
TI - Evidence of a cubic iron sub-lattice in t-CuFe2O4 demonstrated by X-ray
Absorption Fine Structure.
AB - Copper ferrite, belonging to the wide and technologically relevant class of
spinel ferrites, was grown in the form of t-CuFe2O4 nanocrystals within a porous
matrix of silica in the form of either an aerogel or a xerogel, and compared to a
bulk sample. Extended X-ray absorption fine structure (EXAFS) spectroscopy
revealed the presence of two different sub-lattices within the crystal structure
of t-CuFe2O4, one tetragonal and one cubic, defined by the Cu2+ and Fe3+ ions
respectively. Our investigation provides evidence that the Jahn-Teller
distortion, which occurs on the Cu2+ ions located in octahedral sites, does not
affect the coordination geometry of the Fe3+ ions, regardless of their location
in octahedral or tetrahedral sites.
PMID- 29335499
TI - Structure of a MacAB-like efflux pump from Streptococcus pneumoniae.
AB - The spr0693-spr0694-spr0695 operon of Streptococcus pneumoniae encodes a putative
ATP-binding cassette (ABC)-type efflux pump involved in the resistance of
antibiotics and antimicrobial peptides. Here we report the crystal structures of
Spr0694-0695 at 3.3 A and Spr0693 at 3.0 A resolution, revealing a MacAB-like
efflux pump. The dimeric Spr0694-0695 adopts a non-canonical fold of ABC
transporter, the transmembrane domain of which consists of eight tightly packed
transmembrane helices with an insertion of extracellular domain between the first
and second helices, whereas Spr0693 forms a nanotube channel docked onto the ABC
transporter. Structural analyses combined with ATPase activity and antimicrobial
susceptibility assays, enable us to propose a putative substrate-entrance tunnel
with a lateral access controlled by a guard helix. Altogether, our findings
provide structural insights and putative transport mechanism of a MacAB-like
efflux pump in Gram-positive bacteria.
PMID- 29335501
TI - Dual functional dinuclear platinum complex with selective reactivity towards c
myc G-quadruplex.
AB - G-quadruplexes (GQ) folded by the oncogenic G-rich sequences are the promising
targets for developing anticancer therapeutic molecules. However, the current
drug development mainly focused on non-covalent dynamic binders to stabilize GQ
structures, while the covalent targeting from inorganic complexes via chelating
principles, as a potent therapeutic strategy was surprisingly lack of
exploration. Herein, a series of dinuclear platinum complexes, [(Pt(Dip)Cl)2(MU
diamine)](NO3)2 (Dip: 4,7-diphenyl-1,10-phenanthroline), were designed to contain
two dual-functional Pt cores connected by an alkyl linkage. Pt3 with
nonanediamine linkage optimized the specific binding towards c-myc G-quadruplex
via dual functional clamp on GQ as 1) non-covalently pi-stacking of aromatic
ligands, and 2) two Pt(II) cores covalently chelated to guanines at both 3'- and
5'-ends.
PMID- 29335502
TI - The space charge limited current and huge linear magnetoresistance in silicon.
AB - Huge magnetoresistance in space charge regime attracts broad interest on non
equilibrium carrier transport under high electric field. However, the accurate
fitting for the current-voltage curves from Ohmic to space charge regime under
magnetic fields has not been achieved quantitatively. We conjecture that the
localized intensive charge dynamic should be taken into consideration. Here, by
introducing a field-dependent dielectric constant, for the first time, we
successfully simulate the current-voltage curves of covalent crystal silicon
wafers under different magnetic fields (0-1 Tesla). The simulation reveals that
the optical phonon, instead of the acoustic phonon, plays a major role for the
carriers transport under magnetic fields in space charge regime.
PMID- 29335503
TI - Tuning charge carrier transport and optical birefringence in liquid-crystalline
thin films: A new design space for organic light-emitting diodes.
AB - Liquid-crystalline organic semiconductors exhibit unique properties that make
them highly interesting for organic optoelectronic applications. Their optical
and electrical anisotropies and the possibility to control the alignment of the
liquid-crystalline semiconductor allow not only to optimize charge carrier
transport, but to tune the optical property of organic thin-film devices as well.
In this study, the molecular orientation in a liquid-crystalline semiconductor
film is tuned by a novel blading process as well as by different annealing
protocols. The altered alignment is verified by cross-polarized optical
microscopy and spectroscopic ellipsometry. It is shown that a change in alignment
of the liquid-crystalline semiconductor improves charge transport in single
charge carrier devices profoundly. Comparing the current-voltage characteristics
of single charge carrier devices with simulations shows an excellent agreement
and from this an in-depth understanding of single charge carrier transport in two
terminal devices is obtained. Finally, p-i-n type organic light-emitting diodes
(OLEDs) compatible with vacuum processing techniques used in state-of-the-art
OLEDs are demonstrated employing liquid-crystalline host matrix in the emission
layer.
PMID- 29335504
TI - Testing for the Presence of Correlation Changes in a Multivariate Time Series: A
Permutation Based Approach.
AB - Detecting abrupt correlation changes in multivariate time series is crucial in
many application fields such as signal processing, functional neuroimaging,
climate studies, and financial analysis. To detect such changes, several
promising correlation change tests exist, but they may suffer from severe loss of
power when there is actually more than one change point underlying the data. To
deal with this drawback, we propose a permutation based significance test for
Kernel Change Point (KCP) detection on the running correlations. Given a
requested number of change points K, KCP divides the time series into K + 1
phases by minimizing the within-phase variance. The new permutation test looks at
how the average within-phase variance decreases when K increases and compares
this to the results for permuted data. The results of an extensive simulation
study and applications to several real data sets show that, depending on the
setting, the new test performs either at par or better than the state-of-the art
significance tests for detecting the presence of correlation changes, implying
that its use can be generally recommended.
PMID- 29335505
TI - PERK-mediated translational control is required for collagen secretion in
chondrocytes.
AB - As chondrocytes are highly secretory and they experience a variety of stresses,
physiological unfolded protein response (UPR) signalling is essential for
extracellular matrix (ECM) secretion and chondrogenesis. In the three branches of
the UPR pathway, PERK governs the translational attenuation and transcriptional
upregulation of amino acid and redox metabolism and induction of apoptosis. It
was previously demonstrated that a defect of the PERK branch of the UPR
signalling pathway causes the accumulation of unfolded proteins, leading to cell
death without perturbing endoplasmic reticulum (ER)-to-Golgi transport in
pancreatic beta cells. However, little is known about the role of PERK in
chondrocytes. In this study, we found that PERK signalling is activated in
chondrocytes, and inhibition of PERK reduces collagen secretion despite causing
excessive collagen synthesis in the ER. Perk -/- mice displayed reduced collagen
in articular cartilage but no differences in chondrocyte proliferation or
apoptosis compared to the findings in wild-type mice. PERK inhibition increases
misfolded protein levels in the ER, which largely hinder ER-to-Golgi transport.
These results suggest that the translational control mediated by PERK is a
critical determinant of ECM secretion in chondrocytes.
PMID- 29335506
TI - Transcriptome profiling during mangrove viviparity in response to abscisic acid.
AB - Mangrove plants adapt to coastal tidal mudflats with specially evolved viviparity
seed development. However, very little is known about the genetic and molecular
mechanisms of mangrove viviparity. Here, we tested a hypothesis that plant
hormone abscisic acid (ABA) plays a significant role in precocious germination of
viviparous Kandelia obovata seeds by exogenous applications. Through
transcriptome analysis of ABA treated seeds, it was found that ABA repressed
mangrove fruit growth and development, and there were thousands of genes
differentially expressed. As a result, dynamics of the pathways were dramatically
altered. In particular, "Plant hormone signal transduction" and "MAPK signaling
pathway" were represented significantly. Among differentially expressed genes,
some key genes of ABA signal transduction were induced, while ABA biosynthesis
genes were repressed. Take ABI1 and ABI2, key negative regulators in ABA signal
pathway, as examples, homologous alignment and a phylogenetic tree in various
species showed that ABI1 and ABI2 are highly conserved among various species. The
functional similarity of these genes was confirmed by transgenic work in
Arabidopsis. Taken together, ABA inhibited mangrove viviparity, but mangroves
developed a mechanism to prevent accidently increase of ABA in the harsh
environment for maintaining viviparous reproductive strategy.
PMID- 29335508
TI - Label-Free, High Resolution, Multi-Modal Light Microscopy for Discrimination of
Live Stem Cell Differentiation Status.
AB - A label-free microscopy method for assessing the differentiation status of stem
cells is presented with potential application for characterization of therapeutic
stem cell populations. The microscopy system is capable of characterizing live
cells based on the use of evanescent wave microscopy and quantitative phase
contrast (QPC) microscopy. The capability of the microscopy system is
demonstrated by studying the differentiation of live immortalised neonatal mouse
neural stem cells over a 15 day time course. Metrics extracted from microscope
images are assessed and images compared with results from endpoint immuno
staining studies to illustrate the system's performance. Results demonstrate the
potential of the microscopy system as a valuable tool for cell biologists to
readily identify the differentiation status of unlabelled live cells.
PMID- 29335507
TI - Highly conserved molecular pathways, including Wnt signaling, promote functional
recovery from spinal cord injury in lampreys.
AB - In mammals, spinal cord injury (SCI) leads to dramatic losses in neurons and
synaptic connections, and consequently function. Unlike mammals, lampreys are
vertebrates that undergo spontaneous regeneration and achieve functional recovery
after SCI. Therefore our goal was to determine the complete transcriptional
responses that occur after SCI in lampreys and to identify deeply conserved
pathways that promote regeneration. We performed RNA-Seq on lamprey spinal cord
and brain throughout the course of functional recovery. We describe complex
transcriptional responses in the injured spinal cord, and somewhat surprisingly,
also in the brain. Transcriptional responses to SCI in lampreys included
transcription factor networks that promote peripheral nerve regeneration in
mammals such as Atf3 and Jun. Furthermore, a number of highly conserved axon
guidance, extracellular matrix, and proliferation genes were also differentially
expressed after SCI in lampreys. Strikingly, ~3% of differentially expressed
transcripts belonged to the Wnt pathways. These included members of the Wnt and
Frizzled gene families, and genes involved in downstream signaling.
Pharmacological inhibition of Wnt signaling inhibited functional recovery,
confirming a critical role for this pathway. These data indicate that molecular
signals present in mammals are also involved in regeneration in lampreys,
supporting translational relevance of the model.
PMID- 29335510
TI - TiO2 Nanoribbons/Carbon Nanotubes Composite with Enhanced Photocatalytic
Activity; Fabrication, Characterization, and Application.
AB - TiO2 nanoribbons (TiO2 NRs) loaded with FeCo-Al2O3 catalyst were synthesized and
used as a precursor in the synthesis of TiO2 nanoribbons/carbon nanotubes (TiO2
NRs/CNTs) composite by a chemical vapor deposition (CVD) method. TiO2 NRs and
TiO2 NRs/CNTs composite were characterized by XRD, FT-IR, TEM, SEM, EDX and UV
Vis spectrophotometer. The results revealed the formation of TiO2-B and hydrogen
titanate nanoribbon like structures by the hydrothermal treatment. After loading
TiO2 NRs by FeCo-Al2O3 catalyst and the CVD growth of carbon nanotubes, the
synthetic TiO2 nanoribbons converted entirely to TiO2-B nanoribbons with nanopits
structure. The composite composed of tube-like nanostructures forming an
interlocked network from CNTs and TiO2-B NRs. The composite shows a relatively
red-shifted band gap (3.09 eV), broader and stronger UV absorption band relative
to TiO2 NRs. The photocatalytic properties of TiO2 NRs and TiO2 NRs/CNTs
composite were studied under sunlight irradiation. The photocatalytic degradation
of methylene blue (MB) dye was investigated as a function of contact time, dye
concentration, and catalyst dose. The kinetics and mechanisms of degradation were
discussed. TiO2 NRs/CNTs composite showed higher stability after six runs and 50%
shorter irradiation time than TiO2 NRs photocatalyst.
PMID- 29335511
TI - Publisher Correction: Broad modulus range nanomechanical mapping by magnetic
drive soft probes.
AB - In the original version of this Article, the text labels on the bottom-right
graph in Fig. 1c were inadvertently displaced during the production process. This
has now been corrected in both the PDF and HTML versions of the Article.
PMID- 29335509
TI - Salient type 1 interleukin 1 receptor expression in peripheral non-immune cells.
AB - Interleukin 1 is a pleiotropic cytokine that mediates diverse functions through
its receptor, type I interleukin 1 receptor (IL-1R1). Most previous studies have
focused on the expression and function of IL-1R1 in immune cells. Here we
performed a comprehensive mapping of IL-1R1 distribution in multiple peripheral
tissues using our IL-1R1 reporter (IL-1R1GR/GR) mice. This method yielded the
highest sensitivity of in situ detection of IL-1R1 mRNA and protein. Besides
validating previously reported IL-1R1 expression in the endocrine tissues
including pituitary and pancreas, our results refuted previously reported
exclusive IL-1R1 expression in neurons of the spinal cord dorsal horn and dorsal
root ganglia (DRG). Instead, IL-1R1 expression was detected in endothelial cells
within DRG, spinal cord, pancreas, colon, muscles and many immune organs. In
addition, gp38+ fibroblastic reticular cells (FRCs), rather than tissue
macrophages or other immune cells, were found to express high levels of IL-1R1 in
colon and many immune organs. A functional test of spleen FRCs showed that they
responded rapidly to systemic IL-1beta stimulation in vivo. Taken together, this
study provides a rigorous re-examination of IL-1R1 expression in peripheral
tissues and reveals tissue FRCs as a previously unappreciated novel high IL-1R1
expressing cell type in peripheral IL-1 signaling.
PMID- 29335512
TI - Label-free photoacoustic imaging of human palmar vessels: a structural
morphological analysis.
AB - We analysed the vascular morphology of the palm using a photoacoustic tomography
(PAT) instrument with a hemispherical detector array. The three-dimensional (3D)
morphology of blood vessels was determined noninvasively. Overall, 12 females and
11 males were recruited as healthy volunteers. Their ages were distributed almost
evenly from 22 to 59 years. In all cases, many vascular networks were observed
just beneath the skin and were determined to be veins anatomically. To analyse
the major arteries, the layer containing the subcutaneous venous network was
removed from the image. The analysis focused on the common and proper palmar
digital arteries. We used the curvature of these arteries as a parameter to
analyse their morphologies. There was no significant difference in the curvature
between genders when comparing the subjects as a whole. The blood vessel
curvature increased with age. Good agreement was found between the 3D numerical
analysis results and the subjective evaluation of the two-dimensional (2D)
projection image. The PAT system enabled visualization of the 3D features of
blood vessels in the palm and noninvasive analysis of arterial tortuousness.
PMID- 29335513
TI - Optimal ranges of variables for an effective adsorption of lead(II) by the
agricultural waste pomelo (Citrus grandis) peels using Doehlert designs.
AB - The capacity of pomelo peels' adsorption on lead(II) from aqueous solutions
without modifications was investigated and confirmed. Four variables in this
study, pH, temperature, time and initial concentration of lead(II), significantly
affected the adsorption rate of pomelo peels. The prediction model and optimal
ranges of optimized variables were given by Doehlert designs, which made the
selection of variables rapid, flexible and effortless to obtain an adsorption
rate reaching 99.9% and 20 mg/L for initial lead(II) concentration, 3 for pH, 50
degrees C for temperature and 210 min for time was a choice. The higher
correlation coefficient as well as the more consistent value of experimental
equilibrium adsorption capacity of the pseudo-first-order model suggested it bore
a better prediction of the adsorption kinetics than the pseudo-second-order
model. Langmuir model indicated the adsorption mechanism of pomelo peels was
monolayer sorption with the help of both physical adsorption and chemical
bonding, which were demonstrated by scanning electron microscopy and Fourier
transform-infrared, respectively. The ability of pomelo peels to adsorb lead(II)
from aqueous solutions was not interfered with the presence of calcium(II),
magnesium(II), copper(II) and zinc(II). Pomelo peels had the potential to be
utilized in the simultaneous adsorption of toxic heavy metal ions.
PMID- 29335514
TI - Monitoring single-cell gene regulation under dynamically controllable conditions
with integrated microfluidics and software.
AB - Much is still not understood about how gene regulatory interactions control cell
fate decisions in single cells, in part due to the difficulty of directly
observing gene regulatory processes in vivo. We introduce here a novel integrated
setup consisting of a microfluidic chip and accompanying analysis software that
enable long-term quantitative tracking of growth and gene expression in single
cells. The dual-input Mother Machine (DIMM) chip enables controlled and
continuous variation of external conditions, allowing direct observation of gene
regulatory responses to changing conditions in single cells. The Mother Machine
Analyzer (MoMA) software achieves unprecedented accuracy in segmenting and
tracking cells, and streamlines high-throughput curation with a novel leveraged
editing procedure. We demonstrate the power of the method by uncovering several
novel features of an iconic gene regulatory program: the induction of Escherichia
coli's lac operon in response to a switch from glucose to lactose.
PMID- 29335515
TI - Ultrafast consolidation of bulk nanocrystalline titanium alloy through ultrasonic
vibration.
AB - Nanocrystalline (NC) materials have fascinating physical and chemical properties,
thereby they exhibit great prospects in academic and industrial fields. Highly
efficient approaches for fabricating bulk NC materials have been pursued
extensively over past decades. However, the instability of nanograin, which is
sensitive to processing parameters (such as temperature and time), is always a
challenging issue to be solved and remains to date. Herein, we report an
ultrafast nanostructuring strategy, namely ultrasonic vibration consolidation
(UVC). The strategy utilizes internal friction heat, generated from mutually
rubbing between Ti-based metallic glass powders, to heat the glassy alloy rapidly
through its supercooled liquid regime, and accelerated viscous flow bonds the
powders together. Consequently, bulk NC-Ti alloy with grain size ranging from 10
to 70 nm and nearly full density is consolidated in 2 seconds. The novel
consolidation approach proposed here offers a general and highly efficient
pathway for manufacturing bulk nanomaterials.
PMID- 29335516
TI - An evaluation of the effect of pulse-shape on grey and white matter stimulation
in the rat brain.
AB - Despite the current success of neuromodulation, standard biphasic, rectangular
pulse shapes may not be optimal to achieve symptom alleviation. Here, we compared
stimulation efficiency (in terms of charge) between complex and standard pulses
in two areas of the rat brain. In motor cortex, Gaussian and interphase gap
stimulation (IPG) increased stimulation efficiency in terms of charge per phase
compared with a standard pulse. Moreover, IPG stimulation of the deep
mesencephalic reticular formation in freely moving rats was more efficient
compared to a standard pulse. We therefore conclude that complex pulses are
superior to standard stimulation, as less charge is required to achieve the same
behavioral effects in a motor paradigm. These results have important implications
for the understanding of electrical stimulation of the nervous system and open
new perspectives for the design of the next generation of safe and efficient
neural implants.
PMID- 29335517
TI - A versatile MOF-based trap for heavy metal ion capture and dispersion.
AB - Current technologies for removing heavy metal ions are typically metal ion
specific. Herein we report the development of a broad-spectrum heavy metal ion
trap by incorporation of ethylenediaminetetraacetic acid into a robust metal
organic framework. The capture experiments for a total of 22 heavy metal ions,
covering hard, soft, and borderline Lewis metal ions, show that the trap is very
effective, with removal efficiencies of >99% for single-component adsorption,
multi-component adsorption, or in breakthrough processes. The material can also
serve as a host for metal ion loading with arbitrary selections of metal ion
amounts/types with a controllable uptake ratio to prepare well-dispersed single
or multiple metal catalysts. This is supported by the excellent performance of
the prepared Pd2+-loaded composite toward the Suzuki coupling reaction. This work
proposes a versatile heavy metal ion trap that may find applications in the
fields of separation and catalysis.
PMID- 29335518
TI - Recurrence patterns after maximal surgical resection and postoperative
radiotherapy in anaplastic gliomas according to the new 2016 WHO classification.
AB - We assessed the appropriateness of current radiotherapy volume for WHO grade III
gliomas. The records of 73 patients with WHO grade III gliomas who received
postoperative radiotherapy between 2001 and 2013 were retrospectively reviewed.
Based on the 2016 WHO classification, 25/73 (34.2%) patients had anaplastic
oligodendroglioma (AO), IDH-mutant and 1p/19q-codeleted; 11/73 (15.1%) patients
had anaplastic astrocytoma, IDH-mutant; and 37/73 (50.7%) patients had anaplastic
astrocytoma, IDH-wildtype. The extent of resection (EOR) was total in 43 patients
(58.9%). The median follow-up time was 84 months. The 5-year overall survival was
65.4%. Of 31 patients with documented recurrences, 20 (64.5%) had infield gross
tumor volume (GTV) failure, six (19.4%) had clinical target volume (CTV)/marginal
failure, and five (16.1%) had outfield failure/seeding. In 13 recurrences among
43 patients who underwent gross total resection (GTR), six (46.2%) had infield
CTV/marginal failure. However, among 30 patients for whom GTR was not conducted,
infield GTV failure was dominant (77.8%). Seventeen patients with AO, IDH-mutant
and 1p/19q-codeleted who underwent GTR experienced no recurrence. In conclusion,
maximal surgical resection and postoperative radiotherapy resulted in a favorable
prognosis, especially in patients with GTR, IDH mutation, and 1p/19q codeletion.
Patterns of failure differed by EOR.
PMID- 29335519
TI - Metabolic reprogramming by PCK1 promotes TCA cataplerosis, oxidative stress and
apoptosis in liver cancer cells and suppresses hepatocellular carcinoma.
AB - Phosphoenolpyruvate carboxykinase (PEPCK or PCK) catalyzes the first rate
limiting step in hepatic gluconeogenesis pathway to maintain blood glucose
levels. Mammalian cells express two PCK genes, encoding for a cytoplasmic (PCPEK
C or PCK1) and a mitochondrial (PEPCK-M or PCK2) isoforms, respectively.
Increased expressions of both PCK genes are found in cancer of several organs,
including colon, lung, and skin, and linked to increased anabolic metabolism and
cell proliferation. Here, we report that the expressions of both PCK1 and PCK2
genes are downregulated in primary hepatocellular carcinoma (HCC) and low PCK
expression was associated with poor prognosis in patients with HCC. Forced
expression of either PCK1 or PCK2 in liver cancer cell lines results in severe
apoptosis under the condition of glucose deprivation and suppressed liver
tumorigenesis in mice. Mechanistically, we show that the pro-apoptotic effect of
PCK1 requires its catalytic activity. We demonstrate that forced PCK1 expression
in glucose-starved liver cancer cells induced TCA cataplerosis, leading to energy
crisis and oxidative stress. Replenishing TCA intermediate alpha-ketoglutarate or
inhibition of reactive oxygen species production blocked the cell death caused by
PCK expression. Taken together, our data reveal that PCK1 is detrimental to
malignant hepatocytes and suggest activating PCK1 expression as a potential
treatment strategy for patients with HCC.
PMID- 29335520
TI - HPV16 E6 and E7 upregulate the histone lysine demethylase KDM2B through the c
MYC/miR-146a-5p axys.
AB - Persistent infection by high-risk human papillomaviruses (HPVs) is associated
with the development of cervical cancer and a subset of anogenital and head and
neck squamous cell carcinomas. Abnormal expression of cellular microRNAs (miRNAs)
plays an important role in the development of cancer, including HPV-related
tumors. In this study, we demonstrated that miR-146a-5p was down-regulated by E6
and, less efficiently, by E7 of high-risk HPV16 in keratinocytes and the presence
of low levels of this miRNA in cervical carcinoma cell lines and in high-risk HPV
positive cervical specimens. Down-regulation of miR-146a-5p was mediated at least
in part by the transcription repressor c-MYC, through binding sites in the miR
146a promoter. Overexpression of miR-146a-5p significantly inhibited
proliferation and migration of keratinocytes and cervical cancer cells. The
histone demethylase KDM2B was validated as a new direct target of miR-146a-5p and
two putative binding sites for miR-146a-5p were identified in its 3'UTR sequence.
Western blot analysis and immunohistochemistry showed that KDM2B was
overexpressed in HPV16 E6/E7-positive keratinocytes, in cervical cancer cell
lines, and in a subset of invasive cervical carcinomas and HPV-positive laryngeal
squamous cell carcinomas. In these tumors, KDM2B overexpression was associated
with c-MYC copy number gain. In vitro, silencing of KDM2B inhibited proliferation
of cervical cancer cells. In conclusion, this study identified a novel player,
the hystone demethylase KDM2B, in HPV-mediated tumorigenesis. E6 and, less
efficiently, E7 of high-risk HPV16 up-regulated KDM2B expression in human
keratinocytes through a pathway involving overexpression of c-MYC, which in turn
downregulated miR-146a-5p.
PMID- 29335521
TI - Non-canonical roles of PFKFB3 in regulation of cell cycle through binding to
CDK4.
AB - There is growing interest in studying the molecular mechanisms of crosstalk
between cancer metabolism and the cell cycle. 6-phosphate fructose-2
kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) is a well-known glycolytic
activator that plays an important role in tumorigenesis. We investigated whether
PFKFB3 was directly involved in oncogenic signaling networks. Mass Spectrometry
showed that PFKFB3 interacts with cyclin-dependent kinase (CDK) 4, which controls
the transition from G1 phase to S phase of the cell cycle. Further analysis
indicated that lysine 147 was a key site for the binding of PFKBFB3 to CDK4.
PFKFB3 binding resulted in the accumulation of CDK4 protein by inhibiting
ubiquitin proteasome degradation mediated by the heat shock protein 90-Cdc37-CDK4
complex. The proteasome-dependent degradation of CDK4 was accelerated by
disrupting the interaction of PFKFB3 with CDK4 by mutating lysine (147) to
alanine. Blocking PFKFB3-CDK4 interaction improved the therapeutic effect of FDA
approved CDK4 inhibitor palbociclib on breast cancer. These findings suggest that
PFKFB3 is a hub for coordinating cell cycle and glucose metabolism. Combined
targeting of PFKFB3 and CDK4 may be new strategy for breast cancer treatment.
PMID- 29335522
TI - Pyruvate kinase M2 promotes pancreatic ductal adenocarcinoma invasion and
metastasis through phosphorylation and stabilization of PAK2 protein.
AB - Pyruvate kinase muscle isozymes (PKMs) have crucial roles in regulating metabolic
changes during carcinogenesis. A switch from PKM1 to PKM2 isoform was thought to
lead to aerobic glycolysis promoting carcinogenesis, and was considered as one of
the cancer signatures. However, recent evidence has argued against the existence
of PKM isoform switch and related metabolic effects during cancer progression. We
compared the effects of PKM1 and PKM2 in cell invasiveness and metastasis of
pancreatic ductal adenocarcinoma (PDAC). Both PKM1 and PKM2 expression affected
cell migration and invasion abilities of PDAC cells, but only knockdown of PKM2
suppressed metastasis in a xenograft model. By comparing the established PKM2
mutants in the regulation of cell invasion, we found that PKM2 may control cell
mobility through its protein kinase and phopho-peptide binding abilities. Further
survey for PKM2-associated proteins identified PAK2 as a possible phosphorylation
target in PDAC. In vitro binding and kinase assays revealed that PKM2 directly
phosphorylated PAK2 at Ser20, Ser141, and Ser192/197. Knockdown of PKM2 decreased
PAK2 protein half-life by increasing ubiquitin-dependent proteasomal degradation.
Moreover, we identified PAK2 as an HSP90 client protein and the mutation at
Ser192/197 of PAK2 reduced PAK2-HSP90 association. Knockdown of PAK2 diminished
in vitro cell mobility and in vivo metastatic ability of PKM2 overexpressed PDAC
cells. PKM2 and PAK2 protein expression also positively correlated with each
other in PDAC tissues. Our findings indicate that PKM2-PAK2 regulation is
critical for developing metastasis in PDAC, and suggest that targeting the
PKM2/HSP90/PAK2 complex has a potential therapeutic value in this deadly disease.
PMID- 29335524
TI - Kidney cancer in 2017: Challenging and refining treatment paradigms.
PMID- 29335523
TI - miR-139-5p inhibits aerobic glycolysis, cell proliferation, migration, and
invasion in hepatocellular carcinoma via a reciprocal regulatory interaction with
ETS1.
AB - Cancer cells have metabolic features that allow them to preferentially metabolize
glucose through aerobic glycolysis, providing them with a progression advantage.
However, microRNA (miRNA) regulation of aerobic glycolysis in cancer cells has
not been extensively investigated. We addressed this in the present study by
examining the regulation of miR-139-5p on aerobic glycolysis of hepatocellular
carcinoma (HCC) using clinical specimens, HCC cells, and a mouse xenograft model.
We found that overexpressing miR-139-5p restrained aerobic glycolysis,
suppressing proliferation, migration, and invasion in HCC cells. miR-139-5p
regulated hexokinase 1 (HK1) and 6-phosphofructo-2-kinase/fructose-2,6
biphosphatase 3 (PFKFB3) expression by directly targeting the transcription
factor ETS1, which bound to the promoters of the HK1 and PFKFB3 genes. miR-139-5p
induced aerobic glycolysis, proliferation, migration, and invasion were reversed
by ETS1 overexpression, while ETS1 silencing induced the expression of miR-139-5p
via a post-transcriptional regulation mode involving Drosha. miR-139-5p
expression was reduced in HCC compared to para-carcinoma tissue, which was
confirmed in The Cancer Genome Atlas and GSE54751 HCC cohorts. Notably, the lower
expression of mir-139 was correlated with worse prognosis. These outcomes
indicate that reciprocal regulatory interactions between miR-139-5p and ETS1
modulate aerobic glycolysis, proliferation, and metastasis in HCC cells,
suggesting new targets for HCC treatment.
PMID- 29335525
TI - Urothelial cancer: Optimizing and integrating cisplatin-based chemotherapy across
the disease spectrum.
PMID- 29335526
TI - Prostate cancer: Race and prostate cancer personalized medicine: the future.
PMID- 29335527
TI - Myosin-Va is required for preciliary vesicle transportation to the mother
centriole during ciliogenesis.
AB - Primary cilia play essential roles in signal transduction and development. The
docking of preciliary vesicles at the distal appendages of a mother centriole is
an initial/critical step of ciliogenesis, but the mechanisms are unclear. Here,
we demonstrate that myosin-Va mediates the transportation of preciliary vesicles
to the mother centriole and reveal the underlying mechanism. We also show that
the myosin-Va-mediated transportation of preciliary vesicles is the earliest
event that defines the onset of ciliogenesis. Depletion of myosin-Va
significantly inhibits the attachment of preciliary vesicles to the distal
appendages of the mother centriole and decreases cilia assembly. Myosin-Va
functions upstream of EHD1- and Rab11-mediated ciliary vesicle formation.
Importantly, dynein mediates myosin-Va-associated preciliary vesicle
transportation to the pericentrosomal region along microtubules, while myosin-Va
mediates preciliary vesicle transportation from the pericentrosomal region to the
distal appendages of the mother centriole via the Arp2/3-associated branched
actin network.
PMID- 29335528
TI - EXD2 governs germ stem cell homeostasis and lifespan by promoting mitoribosome
integrity and translation.
AB - Mitochondria are subcellular organelles that are critical for meeting the
bioenergetic and biosynthetic needs of the cell. Mitochondrial function relies on
genes and RNA species encoded both in the nucleus and mitochondria, and on their
coordinated translation, import and respiratory complex assembly. Here, we
characterize EXD2 (exonuclease 3'-5' domain-containing 2), a nuclear-encoded
gene, and show that it is targeted to the mitochondria and prevents the aberrant
association of messenger RNAs with the mitochondrial ribosome. Loss of EXD2
results in defective mitochondrial translation, impaired respiration, reduced ATP
production, increased reactive oxygen species and widespread metabolic
abnormalities. Depletion of the Drosophila melanogaster EXD2 orthologue (CG6744)
causes developmental delays and premature female germline stem cell attrition,
reduced fecundity and a dramatic extension of lifespan that is reversed with an
antioxidant diet. Our results define a conserved role for EXD2 in mitochondrial
translation that influences development and ageing.
PMID- 29335529
TI - Transient Scute activation via a self-stimulatory loop directs enteroendocrine
cell pair specification from self-renewing intestinal stem cells.
AB - The process through which multiple types of cell-lineage-restricted progenitor
cells are specified from multipotent stem cells is unclear. Here we show that, in
intestinal stem cell lineages in adult Drosophila, in which the Delta-Notch
signalling-guided progenitor cell differentiation into enterocytes is the default
mode, the specification of enteroendocrine cells (EEs) is initiated by transient
Scute activation in a process driven by transcriptional self-stimulation combined
with a negative feedback regulation between Scute and Notch targets. Scute
activation induces asymmetric intestinal stem cell divisions that generate EE
progenitor cells. The mitosis-inducing and fate-inducing activities of Scute
guide each EE progenitor cell to divide exactly once prior to its terminal
differentiation, yielding a pair of EEs. The transient expression of a fate
inducer therefore specifies both type and numbers of committed progenitor cells
originating from stem cells, which could represent a general mechanism used for
diversifying committed progenitor cells from multipotent stem cells.
PMID- 29335530
TI - Segregation of mitochondrial DNA heteroplasmy through a developmental genetic
bottleneck in human embryos.
AB - Mitochondrial DNA (mtDNA) mutations cause inherited diseases and are implicated
in the pathogenesis of common late-onset disorders, but how they arise is not
clear1,2. Here we show that mtDNA mutations are present in primordial germ cells
(PGCs) within healthy female human embryos. Isolated PGCs have a profound
reduction in mtDNA content, with discrete mitochondria containing ~5 mtDNA
molecules. Single-cell deep mtDNA sequencing of in vivo human female PGCs showed
rare variants reaching higher heteroplasmy levels in late PGCs, consistent with
the observed genetic bottleneck. We also saw the signature of selection against
non-synonymous protein-coding, tRNA gene and D-loop variants, concomitant with a
progressive upregulation of genes involving mtDNA replication and transcription,
and linked to a transition from glycolytic to oxidative metabolism. The
associated metabolic shift would expose deleterious mutations to selection during
early germ cell development, preventing the relentless accumulation of mtDNA
mutations in the human population predicted by Muller's ratchet. Mutations
escaping this mechanism will show shifts in heteroplasmy levels within one human
generation, explaining the extreme phenotypic variation seen in human pedigrees
with inherited mtDNA disorders.
PMID- 29335531
TI - Publisher Correction: Coherent diffractive imaging of single helium nanodroplets
with a high harmonic generation source.
AB - In the original version of this Article, the affiliation for Luca Poletto was
incorrectly given as 'European XFEL GmbH, Holzkoppel 4, 22869 Schenefeld,
Hamburg, Germany', instead of the correct 'CNR, Istituto di Fotonica e
Nanotecnologie Padova, Via Trasea 7, 35131 Padova, Italy'. This has now been
corrected in both the PDF and HTML versions of the Article.
PMID- 29335532
TI - Intelligent image-based in situ single-cell isolation.
AB - Quantifying heterogeneities within cell populations is important for many fields
including cancer research and neurobiology; however, techniques to isolate
individual cells are limited. Here, we describe a high-throughput, non
disruptive, and cost-effective isolation method that is capable of capturing
individually targeted cells using widely available techniques. Using high
resolution microscopy, laser microcapture microscopy, image analysis, and machine
learning, our technology enables scalable molecular genetic analysis of single
cells, targetable by morphology or location within the sample.
PMID- 29335533
TI - Fc-modified exenatide-loaded nanoparticles for oral delivery to improve
hypoglycemic effects in mice.
AB - To improve the oral efficiency of exenatide, we prepared polyethylene glycol
poly(lactic-co-glycolic acid) (PEG-PLGA) NPs modified with Fc (NPs-Fc) for
exenatide oral delivery. Exenatide was encapsulated into the NPs by the w/o/w
emulsion-solvent evaporation method. The particle size of the NPs-Fc was
approximately 30 nm larger than that of the unmodified NPs with polydispersity
indices in a narrow range (PDIs; PDI < 0.3) as detected by DLS, and the highest
encapsulation efficiency of exenatide in the NPs was greater than 80%. Fc
conjugated NPs permeated Caco-2 cells faster and to a greater extent compared to
unmodified NPs, as verified by CLSM and flow cytometry. Hypoglycemic effect
studies demonstrated that oral administration of exenatide-loaded PEG-PLGA NPs
modified by an Fc group extended the hypoglycemic effects compared with s.c.
injection of the exenatide solution. Fluorescence-labeled NPs were used to
investigate the effects of Fc targeting, and the results demonstrated that the
NPs-Fc stayed in the gastrointestinal tract for a longer time in comparison with
the unmodified NPs, as shown by the whole-body fluorescence images and
fluorescence images of the dissected organs detected by in vivo imaging in live
mice. Therefore, Fc-targeted nano-delivery systems show great promise for oral
peptide/protein drug delivery.
PMID- 29335534
TI - Cell-type specific potent Wnt signaling blockade by bispecific antibody.
AB - Cell signaling pathways are often shared between normal and diseased cells. How
to achieve cell type-specific, potent inhibition of signaling pathways is a major
challenge with implications for therapeutic development. Using the Wnt/beta
catenin signaling pathway as a model system, we report here a novel and generally
applicable method to achieve cell type-selective signaling blockade. We
constructed a bispecific antibody targeting the Wnt co-receptor LRP6 (the
effector antigen) and a cell type-associated antigen (the guide antigen) that
provides the targeting specificity. We found that the bispecific antibody
inhibits Wnt-induced reporter activities with over one hundred-fold enhancement
in potency, and in a cell type-selective manner. Potency enhancement is dependent
on the expression level of the guide antigen on the target cell surface and the
apparent affinity of the anti-guide antibody. Both internalizing and non
internalizing guide antigens can be used, with internalizing bispecific antibody
being able to block signaling by all ligands binding to the target receptor due
to its removal from the cell surface. It is thus feasible to develop bispecific
based therapeutic strategies that potently and selectively inhibit signaling
pathways in a cell type-selective manner, creating opportunity for therapeutic
targeting.
PMID- 29335535
TI - A multi-omics study of the grapevine-downy mildew (Plasmopara viticola)
pathosystem unveils a complex protein coding- and noncoding-based arms race
during infection.
AB - Fungicides are applied intensively to prevent downy mildew infections of
grapevines (Vitis vinifera) with high impact on the environment. In order to
develop alternative strategies we sequenced the genome of the oomycete pathogen
Plasmopara viticola causing this disease. We show that it derives from a
Phytophthora-like ancestor that switched to obligate biotrophy by losing genes
involved in nitrogen metabolism and gamma-Aminobutyric acid catabolism. By
combining multiple omics approaches we characterized the pathosystem and
identified a RxLR effector that trigger an immune response in the wild species V.
riparia. This effector is an ideal marker to screen novel grape resistant
varieties. Our study reveals an unprecedented bidirectional noncoding RNA-based
mechanism that, in one direction might be fundamental for P. viticola to
proficiently infect its host, and in the other might reduce the effects of the
infection on the plant.
PMID- 29335536
TI - Characterizing the dynamics underlying global spread of epidemics.
AB - Over the past few decades, global metapopulation epidemic simulations built with
worldwide air-transportation data have been the main tool for studying how
epidemics spread from the origin to other parts of the world (e.g., for pandemic
influenza, SARS, and Ebola). However, it remains unclear how disease epidemiology
and the air-transportation network structure determine epidemic arrivals for
different populations around the globe. Here, we fill this knowledge gap by
developing and validating an analytical framework that requires only basic
analytics from stochastic processes. We apply this framework retrospectively to
the 2009 influenza pandemic and 2014 Ebola epidemic to show that key epidemic
parameters could be robustly estimated in real-time from public data on local and
global spread at very low computational cost. Our framework not only elucidates
the dynamics underlying global spread of epidemics but also advances our
capability in nowcasting and forecasting epidemics.
PMID- 29335537
TI - A bony-crested Jurassic dinosaur with evidence of iridescent plumage highlights
complexity in early paravian evolution.
AB - The Jurassic Yanliao theropods have offered rare glimpses of the early paravian
evolution and particularly of bird origins, but, with the exception of the
bizarre scansoriopterygids, they have shown similar skeletal and integumentary
morphologies. Here we report a distinctive new Yanliao theropod species bearing
prominent lacrimal crests, bony ornaments previously known from more basal
theropods. It shows longer arm and leg feathers than Anchiornis and tail feathers
with asymmetrical vanes forming a tail surface area even larger than that in
Archaeopteryx. Nanostructures, interpreted as melanosomes, are morphologically
similar to organized, platelet-shaped organelles that produce bright iridescent
colours in extant birds. The new species indicates the presence of bony
ornaments, feather colour and flight-related features consistent with proposed
rapid character evolution and significant diversity in signalling and locomotor
strategies near bird origins.
PMID- 29335538
TI - Speed-related activation in the mesolimbic dopamine system during the observation
of driver-view videos.
AB - Despite the ubiquity and importance of speeding offenses, there has been little
neuroscience research regarding the propensity for speeding among vehicle
drivers. In the current study, as a first attempt, we examined the hypothesis
that visual inputs during high-speed driving would activate the mesolimbic
dopaminergic system that plays an important role in mediating motivational
craving. To this end, we used functional magnetic resonance imaging to identify
speed-related activation changes in mesolimbic dopaminergic regions during the
observation of driver-view videos in two groups that differed in self-reported
speeding propensity. Results revealed, as we expected, greater activation in the
ventral tegmental area (VTA) in response to driver-view videos with higher speed.
Contrary to our expectation, however, we found no significant between-group
difference in speed-related activation changes in mesolimbic dopaminergic
regions. Instead, an exploratory psychophysiological interaction analysis found
that self-reported speeding propensity was associated with speed-related
functional coupling between the VTA and the right intraparietal sulcus. Further
validation of our hypothesis will require future studies examining associations
between speed-related activation in the mesolimbic dopaminergic system and
individual differences in speeding propensity, using a more reliable measure of
actual speeding propensity in real traffic.
PMID- 29335540
TI - Publisher Correction: Acoustic allometry revisited: morphological determinants of
fundamental frequency in primate vocal production.
AB - A correction to this article has been published and is linked from the HTML
version of this paper. The error has not been fixed in the paper.
PMID- 29335539
TI - Brain activity patterns in high-throughput electrophysiology screen predict both
drug efficacies and side effects.
AB - Neurological drugs are often associated with serious side effects, yet drug
screens typically focus only on efficacy. We demonstrate a novel paradigm
utilizing high-throughput in vivo electrophysiology and brain activity patterns
(BAPs). A platform with high sensitivity records local field potentials (LFPs)
simultaneously from many zebrafish larvae over extended periods. We show that
BAPs from larvae experiencing epileptic seizures or drug-induced side effects
have substantially reduced complexity (entropy), similar to reduced LFP
complexity observed in Parkinson's disease. To determine whether drugs that
enhance BAP complexity produces positive outcomes, we used light pulses to
trigger seizures in a model of Dravet syndrome, an intractable genetic epilepsy.
The highest-ranked compounds identified by BAP analysis exhibit far greater anti
seizure efficacy and fewer side effects during subsequent in-depth behavioral
assessment. This high correlation with behavioral outcomes illustrates the power
of brain activity pattern-based screens and identifies novel therapeutic
candidates with minimal side effects.
PMID- 29335541
TI - Modulation of UVB-induced Carcinogenesis by Activation of Alternative DNA Repair
Pathways.
AB - The molecular basis for ultraviolet (UV) light-induced nonmelanoma and melanoma
skin cancers centers on cumulative genomic instability caused by inefficient DNA
repair of dipyrimidine photoproducts. Inefficient DNA repair and subsequent
translesion replication past these DNA lesions generate distinct molecular
signatures of tandem CC to TT and C to T transitions at dipyrimidine sites. Since
previous efforts to develop experimental strategies to enhance the repair
capacity of basal keratinocytes have been limited, we have engineered the N
terminally truncated form (Delta228) UV endonuclease (UVDE) from
Schizosaccharomyces pombe to include a TAT cell-penetrating peptide sequence with
or without a nuclear localization signal (NLS): UVDE-TAT and UVDE-NLS-TAT.
Further, a NLS was engineered onto a pyrimidine dimer glycosylase from Paramecium
bursaria chlorella virus-1 (cv-pdg-NLS). Purified enzymes were encapsulated into
liposomes and topically delivered to the dorsal surface of SKH1 hairless mice in
a UVB-induced carcinogenesis study. Total tumor burden was significantly reduced
in mice receiving either UVDE-TAT or UVDE-NLS-TAT versus control empty liposomes
and time to death was significantly reduced with the UVDE-NLS-TAT. These data
suggest that efficient delivery of exogenous enzymes for the initiation of repair
of UVB-induced DNA damage may protect from UVB induction of squamous and basal
cell carcinomas.
PMID- 29335543
TI - Genetics of lipid metabolism in prostate cancer.
PMID- 29335542
TI - Compartmentalized activities of the pyruvate dehydrogenase complex sustain
lipogenesis in prostate cancer.
AB - The mechanisms by which mitochondrial metabolism supports cancer anabolism remain
unclear. Here, we found that genetic and pharmacological inactivation of pyruvate
dehydrogenase A1 (PDHA1), a subunit of the pyruvate dehydrogenase complex (PDC),
inhibits prostate cancer development in mouse and human xenograft tumor models by
affecting lipid biosynthesis. Mechanistically, we show that in prostate cancer,
PDC localizes in both the mitochondria and the nucleus. Whereas nuclear PDC
controls the expression of sterol regulatory element-binding transcription factor
(SREBF)-target genes by mediating histone acetylation, mitochondrial PDC provides
cytosolic citrate for lipid synthesis in a coordinated manner, thereby sustaining
anabolism. Additionally, we found that PDHA1 and the PDC activator pyruvate
dehydrogenase phosphatase 1 (PDP1) are frequently amplified and overexpressed at
both the gene and protein levels in prostate tumors. Together, these findings
demonstrate that both mitochondrial and nuclear PDC sustain prostate
tumorigenesis by controlling lipid biosynthesis, thus suggesting this complex as
a potential target for cancer therapy.
PMID- 29335544
TI - Transposon-derived small RNAs triggered by miR845 mediate genome dosage response
in Arabidopsis.
AB - Chromosome dosage has substantial effects on reproductive isolation and
speciation in both plants and animals, but the underlying mechanisms are largely
obscure 1 . Transposable elements in animals can regulate hybridity through
maternal small RNA 2 , whereas small RNAs in plants have been postulated to
regulate dosage response via neighboring imprinted genes3,4. Here we show that a
highly conserved microRNA in plants, miR845, targets the tRNAMet primer-binding
site (PBS) of long terminal repeat (LTR) retrotransposons in Arabidopsis pollen,
and triggers the accumulation of 21-22-nucleotide (nt) small RNAs in a dose
dependent fashion via RNA polymerase IV. We show that these epigenetically
activated small interfering RNAs (easiRNAs) mediate hybridization barriers
between diploid seed parents and tetraploid pollen parents (the 'triploid
block'), and that natural variation for miR845 may account for 'endosperm
balance' allowing the formation of triploid seeds. Targeting of the PBS with
small RNA is a common mechanism for transposon control in mammals and plants, and
provides a uniquely sensitive means to monitor chromosome dosage and imprinting
in the developing seed.
PMID- 29335545
TI - An aberrant SREBP-dependent lipogenic program promotes metastatic prostate
cancer.
AB - Lipids, either endogenously synthesized or exogenous, have been linked to human
cancer. Here we found that PML is frequently co-deleted with PTEN in metastatic
human prostate cancer (CaP). We demonstrated that conditional inactivation of Pml
in the mouse prostate morphs indolent Pten-null tumors into lethal metastatic
disease. We identified MAPK reactivation, subsequent hyperactivation of an
aberrant SREBP prometastatic lipogenic program, and a distinctive lipidomic
profile as key characteristic features of metastatic Pml and Pten double-null
CaP. Furthermore, targeting SREBP in vivo by fatostatin blocked both tumor growth
and distant metastasis. Importantly, a high-fat diet (HFD) induced lipid
accumulation in prostate tumors and was sufficient to drive metastasis in a
nonmetastatic Pten-null mouse model of CaP, and an SREBP signature was highly
enriched in metastatic human CaP. Thus, our findings uncover a prometastatic
lipogenic program and lend direct genetic and experimental support to the notion
that a Western HFD can promote metastasis.
PMID- 29335547
TI - Pan-genome analysis highlights the extent of genomic variation in cultivated and
wild rice.
AB - The rich genetic diversity in Oryza sativa and Oryza rufipogon serves as the main
sources in rice breeding. Large-scale resequencing has been undertaken to
discover allelic variants in rice, but much of the information for genetic
variation is often lost by direct mapping of short sequence reads onto the O.
sativa japonica Nipponbare reference genome. Here we constructed a pan-genome
dataset of the O. sativa-O. rufipogon species complex through deep sequencing and
de novo assembly of 66 divergent accessions. Intergenomic comparisons identified
23 million sequence variants in the rice genome. This catalog of sequence
variations includes many known quantitative trait nucleotides and will be helpful
in pinpointing new causal variants that underlie complex traits. In particular,
we systemically investigated the whole set of coding genes using this pan-genome
data, which revealed extensive presence and absence of variation among rice
accessions. This pan-genome resource will further promote evolutionary and
functional studies in rice.
PMID- 29335546
TI - Transcription factors orchestrate dynamic interplay between genome topology and
gene regulation during cell reprogramming.
AB - Chromosomal architecture is known to influence gene expression, yet its role in
controlling cell fate remains poorly understood. Reprogramming of somatic cells
into pluripotent stem cells (PSCs) by the transcription factors (TFs) OCT4, SOX2,
KLF4 and MYC offers an opportunity to address this question but is severely
limited by the low proportion of responding cells. We have recently developed a
highly efficient reprogramming protocol that synchronously converts somatic into
pluripotent stem cells. Here, we used this system to integrate time-resolved
changes in genome topology with gene expression, TF binding and chromatin-state
dynamics. The results showed that TFs drive topological genome reorganization at
multiple architectural levels, often before changes in gene expression. Removal
of locus-specific topological barriers can explain why pluripotency genes are
activated sequentially, instead of simultaneously, during reprogramming.
Together, our results implicate genome topology as an instructive force for
implementing transcriptional programs and cell fate in mammals.
PMID- 29335548
TI - Paternal easiRNAs regulate parental genome dosage in Arabidopsis.
AB - The regulation of parental genome dosage is of fundamental importance in animals
and plants, as exemplified by X-chromosome inactivation and dosage compensation.
The 'triploid block' is a classic example of dosage regulation in plants that
establishes a reproductive barrier between species differing in chromosome
number1,2. This barrier acts in the embryo-nourishing endosperm tissue and
induces the abortion of hybrid seeds through a yet unknown mechanism 3 . Here we
show that depletion of paternal epigenetically activated small interfering RNAs
(easiRNAs) bypasses the triploid block in response to increased paternal ploidy
in Arabidopsis thaliana. Paternal loss of the plant-specific RNA polymerase IV
suppressed easiRNA formation and rescued triploid seeds by restoring small-RNA
directed DNA methylation at transposable elements (TEs), correlating with reduced
expression of paternally expressed imprinted genes (PEGs). Our data suggest that
easiRNAs form a quantitative signal for paternal chromosome number and that their
balanced dosage is required for post-fertilization genome stability and seed
viability.
PMID- 29335549
TI - Reconstructing an African haploid genome from the 18th century.
AB - A genome is a mosaic of chromosome fragments from ancestors who existed some
arbitrary number of generations earlier. Here, we reconstruct the genome of Hans
Jonatan (HJ), born in the Caribbean in 1784 to an enslaved African mother and
European father. HJ migrated to Iceland in 1802, married and had two children. We
genotyped 182 of his 788 descendants using single-nucleotide polymorphism (SNP)
chips and whole-genome sequenced (WGS) 20 of them. Using these data, we
reconstructed 38% of HJ's maternal genome and inferred that his mother was from
the region spanned by Benin, Nigeria and Cameroon.
PMID- 29335550
TI - The PEG-responding desiccome of the alder microsymbiont Frankia alni.
AB - Actinorhizal plants are ecologically and economically important. Symbiosis with
nitrogen-fixing bacteria allows these woody dicotyledonous plants to colonise
soils under nitrogen deficiency, water-stress or other extreme conditions.
However, proteins involved in xerotolerance of symbiotic microorganisms have yet
to be identified. Here we characterise the polyethylene glycol (PEG)-responding
desiccome from the most geographically widespread Gram-positive nitrogen-fixing
plant symbiont, Frankia alni, by next-generation proteomics, taking advantage of
a Q-Exactive HF tandem mass spectrometer equipped with an ultra-high-field
Orbitrap analyser. A total of 2,052 proteins were detected and quantified. Under
osmotic stress, PEG-grown F. alni cells increased the abundance of envelope
associated proteins like ABC transporters, mechano-sensitive ion channels and
Clustered Regularly Interspaced Short Palindromic Repeats CRISPR-associated (cas)
components. Conjointly, dispensable pathways, like nitrogen fixation, aerobic
respiration and homologous recombination, were markedly down-regulated. Molecular
modelling and docking simulations suggested that the PEG is acting on Frankia
partly by filling the inner part of an up-regulated osmotic-stress large
conductance mechanosensitive channel.
PMID- 29335552
TI - A pathway for biological methane production using bacterial iron-only
nitrogenase.
AB - Methane (CH4) is a potent greenhouse gas that is released from fossil fuels and
is also produced by microbial activity, with at least one billion tonnes of CH4
being formed and consumed by microorganisms in a single year 1 . Complex
methanogenesis pathways used by archaea are the main route for bioconversion of
carbon dioxide (CO2) to CH4 in nature2-4. Here, we report that wild-type iron
iron (Fe-only) nitrogenase from the bacterium Rhodopseudomonas palustris reduces
CO2 simultaneously with nitrogen gas (N2) and protons to yield CH4, ammonia (NH3)
and hydrogen gas (H2) in a single enzymatic step. The amount of CH4 produced by
purified Fe-only nitrogenase was low compared to its other products, but CH4
production by this enzyme in R. palustris was sufficient to support the growth of
an obligate CH4-utilizing Methylomonas strain when the two microorganisms were
grown in co-culture, with oxygen (O2) added at intervals. Other nitrogen-fixing
bacteria that we tested also formed CH4 when expressing Fe-only nitrogenase,
suggesting that this is a general property of this enzyme. The genomes of 9% of
diverse nitrogen-fixing microorganisms from a range of environments encode Fe
only nitrogenase. Our data suggest that active Fe-only nitrogenase, present in
diverse microorganisms, contributes CH4 that could shape microbial community
interactions.
PMID- 29335553
TI - Mutations in ppe38 block PE_PGRS secretion and increase virulence of
Mycobacterium tuberculosis.
AB - Mycobacterium tuberculosis requires a large number of secreted and exported
proteins for its virulence, immune modulation and nutrient uptake. Most of these
proteins are transported by the different type VII secretion systems1,2. The most
recently evolved type VII secretion system, ESX-5, secretes dozens of substrates
belonging to the PE and PPE families, which are named for conserved proline and
glutamic acid residues close to the amino terminus3,4. However, the role of these
proteins remains largely elusive 1 . Here, we show that mutations of ppe38
completely block the secretion of two large subsets of ESX-5 substrates, that is,
PPE-MPTR and PE_PGRS, together comprising >80 proteins. Importantly,
hypervirulent clinical M. tuberculosis strains of the Beijing lineage have such a
mutation and a concomitant loss of secretion 5 . Restoration of PPE38-dependent
secretion partially reverted the hypervirulence phenotype of a Beijing strain,
and deletion of ppe38 in moderately virulent M. tuberculosis increased virulence.
This indicates that these ESX-5 substrates have an important role in virulence
attenuation. Phylogenetic analysis revealed that deletion of ppe38 occurred at
the branching point of the 'modern' Beijing sublineage and is shared by Beijing
outbreak strains worldwide, suggesting that this deletion may have contributed to
their success and global distribution6,7.
PMID- 29335551
TI - Tumor-derived exosomal miR-1247-3p induces cancer-associated fibroblast
activation to foster lung metastasis of liver cancer.
AB - The communication between tumor-derived elements and stroma in the metastatic
niche has a critical role in facilitating cancer metastasis. Yet, the mechanisms
tumor cells use to control metastatic niche formation are not fully understood.
Here we report that in the lung metastatic niche, high-metastatic hepatocellular
carcinoma (HCC) cells exhibit a greater capacity to convert normal fibroblasts to
cancer-associated fibroblasts (CAFs) than low-metastatic HCC cells. We show high
metastatic HCC cells secrete exosomal miR-1247-3p that directly targets B4GALT3,
leading to activation of beta1-integrin-NF-kappaB signaling in fibroblasts.
Activated CAFs further promote cancer progression by secreting pro-inflammatory
cytokines, including IL-6 and IL-8. Clinical data show high serum exosomal miR
1247-3p levels correlate with lung metastasis in HCC patients. These results
demonstrate intercellular crosstalk between tumor cells and fibroblasts is
mediated by tumor-derived exosomes that control lung metastasis of HCC, providing
potential targets for prevention and treatment of cancer metastasis.
PMID- 29335555
TI - Metatranscriptome of human faecal microbial communities in a cohort of adult men.
AB - The gut microbiome is intimately related to human health, but it is not yet known
which functional activities are driven by specific microorganisms' ecological
configurations or transcription. We report a large-scale investigation of 372
human faecal metatranscriptomes and 929 metagenomes from a subset of 308 men in
the Health Professionals Follow-Up Study. We identified a metatranscriptomic
'core' universally transcribed over time and across participants, often by
different microorganisms. In contrast to the housekeeping functions enriched in
this core, a 'variable' metatranscriptome included specialized pathways that were
differentially expressed both across participants and among microorganisms.
Finally, longitudinal metagenomic profiles allowed ecological interaction network
reconstruction, which remained stable over the six-month timespan, as did strain
tracking within and between participants. These results provide an initial
characterization of human faecal microbial ecology into core, subject-specific,
microorganism-specific and temporally variable transcription, and they
differentiate metagenomically versus metatranscriptomically informative aspects
of the human faecal microbiome.
PMID- 29335554
TI - Stability of the human faecal microbiome in a cohort of adult men.
AB - Characterizing the stability of the gut microbiome is important to exploit it as
a therapeutic target and diagnostic biomarker. We metagenomically and
metatranscriptomically sequenced the faecal microbiomes of 308 participants in
the Health Professionals Follow-Up Study. Participants provided four stool
samples-one pair collected 24-72 h apart and a second pair ~6 months later.
Within-person taxonomic and functional variation was consistently lower than
between-person variation over time. In contrast, metatranscriptomic profiles were
comparably variable within and between subjects due to higher within-subject
longitudinal variation. Metagenomic instability accounted for ~74% of
corresponding metatranscriptomic instability. The rest was probably attributable
to sources such as regulation. Among the pathways that were differentially
regulated, most were consistently over- or under-transcribed at each time point.
Together, these results suggest that a single measurement of the faecal
microbiome can provide long-term information regarding organismal composition and
functional potential, but repeated or short-term measures may be necessary for
dynamic features identified by metatranscriptomics.
PMID- 29335556
TI - Thermodynamic insight into stimuli-responsive behaviour of soft porous crystals.
AB - Knowledge of the thermodynamic potential in terms of the independent variables
allows to characterize the macroscopic state of the system. However, in practice,
it is difficult to access this potential experimentally due to irreversible
transitions that occur between equilibrium states. A showcase example of sudden
transitions between (meta)stable equilibrium states is observed for soft porous
crystals possessing a network with long-range structural order, which can
transform between various states upon external stimuli such as pressure,
temperature and guest adsorption. Such phase transformations are typically
characterized by large volume changes and may be followed experimentally by
monitoring the volume change in terms of certain external triggers. Herein, we
present a generalized thermodynamic approach to construct the underlying
Helmholtz free energy as a function of the state variables that governs the
observed behaviour based on microscopic simulations. This concept allows a unique
identification of the conditions under which a material becomes flexible.
PMID- 29335557
TI - A framework for quantifying the relationship between intensity and severity of
impact of disturbance across types of events and species.
AB - Understanding the impacts of natural disturbances on wildlife populations is a
central task for ecologists; in general, the severity of impact of a disturbance
(e.g., the resulting degree of population decline) is likely to depend primarily
on the disturbance intensity (i.e., strength of forcing), type of disturbance,
and species vulnerability. However, differences among disturbance events in the
physical units of forcing and interspecific differences in the temporal
variability of population size under normal (non-disturbance) conditions hinder
comprehensive analysis of disturbance severity. Here, we propose new measures of
disturbance intensity and severity, both represented by the return periods. We
use a meta-analysis to describe the severity-intensity relationship across
various disturbance types and species. The severity and the range of its 95%
confidential interval increased exponentially with increasing intensity. This
nonlinear relationship suggests that physically intense events may have a
catastrophic impact, but their severity cannot be extrapolated from the severity
intensity relationship for weak, frequent disturbance events. The framework we
propose may help to clarify the influence of event types and species traits on
the severity-intensity relationship, as well as to improve our ability to predict
the ecological consequences of various disturbance events of unexperienced
intensity.
PMID- 29335558
TI - Strongly exchange-coupled and surface-state-modulated magnetization dynamics in
Bi2Se3/yttrium iron garnet heterostructures.
AB - Harnessing the spin-momentum locking of topological surface states in conjunction
with magnetic materials is the first step to realize novel topological insulator
based devices. Here, we report strong interfacial coupling in Bi2Se3/yttrium iron
garnet (YIG) bilayers manifested as large interfacial in-plane magnetic
anisotropy (IMA) and enhancement of damping probed by ferromagnetic resonance.
The interfacial IMA and damping enhancement reaches a maximum when the Bi2Se3
film approaches its two-dimensional limit, indicating that topological surface
states play an important role in the magnetization dynamics of YIG. Temperature
dependent ferromagnetic resonance of Bi2Se3/YIG reveals signatures of the
magnetic proximity effect of TC as high as 180 K, an emerging low-temperature
perpendicular magnetic anisotropy competing the high-temperature IMA, and an
increasing exchange effective field of YIG steadily increasing toward low
temperature. Our study sheds light on the effects of topological insulators on
magnetization dynamics, essential for the development of topological insulator
based spintronic devices.
PMID- 29335559
TI - Publisher Correction: Fusion guide RNAs for orthogonal gene manipulation with
Cas9 and Cpf1.
AB - The originally published version of this Article contained an error in the
spelling of the author Da-eun Kim, which was incorrectly given as Da-Eun Kim.
Furthermore, in Figure 1a, the Cas9 protein was positioned incorrectly during
typesetting. These errors have now been corrected in both the PDF and HTML
versions of the Article.
PMID- 29335560
TI - Ligands with 1,10-phenanthroline scaffold for highly regioselective iron
catalyzed alkene hydrosilylation.
AB - Transition-metal-catalyzed alkene hydrosilylation is one of the most important
homogeneous catalytic reactions, and the development of methods that use base
metals, especially iron, as catalysts for this transformation is a growing area
of research. However, the limited number of ligand scaffolds applicable for base
metal-catalyzed alkene hydrosilylation has seriously hindered advances in this
area. Herein, we report the use of 1,10-phenanthroline ligands in base-metal
catalysts for alkene hydrosilylation. In particular, iron catalysts with 2,9
diaryl-1,10-phenanthroline ligands exhibit unexpected reactivity and selectivity
for hydrosilylation of alkenes, including unique benzylic selectivity with
internal alkenes, Markovnikov selectivity with terminal styrenes and 1,3-dienes,
and excellent activity toward aliphatic terminal alkenes. According to the
mechanistic studies, the unusual benzylic selectivity of this hydrosilylation
initiates from pi-pi interaction between the phenyl of the alkene and the
phenanthroline of the ligand. This ligand scaffold and its unique catalytic model
will open possibilities for base-metal-catalyzed hydrosilylation reactions.
PMID- 29335561
TI - Sub-angstrom cryo-EM structure of a prion protofibril reveals a polar clasp.
AB - The atomic structure of the infectious, protease-resistant, beta-sheet-rich and
fibrillar mammalian prion remains unknown. Through the cryo-EM method MicroED, we
reveal the sub-angstrom-resolution structure of a protofibril formed by a wild
type segment from the beta2-alpha2 loop of the bank vole prion protein. The
structure of this protofibril reveals a stabilizing network of hydrogen bonds
that link polar zippers within a sheet, producing motifs we have named 'polar
clasps'.
PMID- 29335562
TI - Cryo-EM structure of the exocyst complex.
AB - The exocyst is an evolutionarily conserved octameric protein complex that
mediates the tethering of post-Golgi secretory vesicles to the plasma membrane
during exocytosis and is implicated in many cellular processes such as cell
polarization, cytokinesis, ciliogenesis and tumor invasion. Using cryo-EM and
chemical cross-linking MS (CXMS), we solved the structure of the Saccharomyces
cerevisiae exocyst complex at an average resolution of 4.4 A. Our model revealed
the architecture of the exocyst and led to the identification of the helical
bundles that mediate the assembly of the complex at its core. Sequence analysis
suggests that these regions are evolutionarily conserved across eukaryotic
systems. Additional cell biological data suggest a mechanism for exocyst assembly
that leads to vesicle tethering at the plasma membrane.
PMID- 29335564
TI - Electrical control of charged carriers and excitons in atomically thin materials.
AB - Electrical confinement and manipulation of charge carriers in semiconducting
nanostructures are essential for realizing functional quantum electronic devices1
3. The unique band structure4-7 of atomically thin transition metal
dichalcogenides (TMDs) offers a new route towards realizing novel 2D quantum
electronic devices, such as valleytronic devices and valley-spin qubits 8 . 2D
TMDs also provide a platform for novel quantum optoelectronic devices9-11 due to
their large exciton binding energy12,13. However, controlled confinement and
manipulation of electronic and excitonic excitations in TMD nanostructures have
been technically challenging due to the prevailing disorder in the material,
preventing accurate experimental control of local confinement and tunnel
couplings14-16. Here we demonstrate a novel method for creating high-quality
heterostructures composed of atomically thin materials that allows for efficient
electrical control of excitations. Specifically, we demonstrate quantum transport
in the gate-defined, quantum-confined region, observing spin-valley locked
quantized conductance in quantum point contacts. We also realize gate-controlled
Coulomb blockade associated with confinement of electrons and demonstrate
electrical control over charged excitons with tunable local confinement
potentials and tunnel couplings. Our work provides a basis for novel quantum opto
electronic devices based on manipulation of charged carriers and excitons.
PMID- 29335563
TI - Visualization and analysis of non-covalent contacts using the Protein Contacts
Atlas.
AB - Visualizations of biomolecular structures empower us to gain insights into
biological functions, generate testable hypotheses, and communicate biological
concepts. Typical visualizations (such as ball and stick) primarily depict
covalent bonds. In contrast, non-covalent contacts between atoms, which govern
normal physiology, pathogenesis, and drug action, are seldom visualized. We
present the Protein Contacts Atlas, an interactive resource of non-covalent
contacts from over 100,000 PDB crystal structures. We developed multiple
representations for visualization and analysis of non-covalent contacts at
different scales of organization: atoms, residues, secondary structure, subunits,
and entire complexes. The Protein Contacts Atlas enables researchers from
different disciplines to investigate diverse questions in the framework of non
covalent contacts, including the interpretation of allostery, disease mutations
and polymorphisms, by exploring individual subunits, interfaces, and protein
ligand contacts and by mapping external information. The Protein Contacts Atlas
is available at http://www.mrc-lmb.cam.ac.uk/pca/ and also through PDBe.
PMID- 29335565
TI - Ballistic Majorana nanowire devices.
AB - Majorana modes are zero-energy excitations of a topological superconductor that
exhibit non-Abelian statistics1-3. Following proposals for their detection in a
semiconductor nanowire coupled to an s-wave superconductor4,5, several tunnelling
experiments reported characteristic Majorana signatures6-11. Reducing disorder
has been a prime challenge for these experiments because disorder can mimic the
zero-energy signatures of Majoranas12-16, and renders the topological properties
inaccessible17-20. Here, we show characteristic Majorana signatures in InSb
nanowire devices exhibiting clear ballistic transport properties. Application of
a magnetic field and spatial control of carrier density using local gates
generates a zero bias peak that is rigid over a large region in the parameter
space of chemical potential, Zeeman energy and tunnel barrier potential. The
reduction of disorder allows us to resolve separate regions in the parameter
space with and without a zero bias peak, indicating topologically distinct
phases. These observations are consistent with the Majorana theory in a ballistic
system 21 , and exclude the known alternative explanations that invoke disorder12
16 or a nonuniform chemical potential22,23.
PMID- 29335566
TI - Tunable confinement of charges and excitations.
PMID- 29335567
TI - Metagenomic analysis of microbial communities yields insight into impacts of
nanoparticle design.
AB - Next-generation DNA sequencing and metagenomic analysis provide powerful tools
for the environmentally friendly design of nanoparticles. Herein we demonstrate
this approach using a model community of environmental microbes (that is,
wastewater-activated sludge) dosed with gold nanoparticles of varying surface
coatings and morphologies. Metagenomic analysis was highly sensitive in detecting
the microbial community response to gold nanospheres and nanorods with either
cetyltrimethylammonium bromide or polyacrylic acid surface coatings. We observed
that the gold-nanoparticle morphology imposes a stronger force in shaping the
microbial community structure than does the surface coating. Trends were
consistent in terms of the compositions of both taxonomic and functional genes,
which include antibiotic resistance genes, metal resistance genes and gene
transfer elements associated with cell stress that are relevant to public health.
Given that nanoparticle morphology remained constant, the potential influence of
gold dissolution was minimal. Surface coating governed the nanoparticle
partitioning between the bioparticulate and aqueous phases.
PMID- 29335568
TI - Strain distributions and their influence on electronic structures of WSe2-MoS2
laterally strained heterojunctions.
AB - Monolayer transition metal dichalcogenide heterojunctions, including vertical and
lateral p-n junctions, have attracted considerable attention due to their
potential applications in electronics and optoelectronics. Lattice-misfit strain
in atomically abrupt lateral heterojunctions, such as WSe2-MoS2, offers a new
band-engineering strategy for tailoring their electronic properties. However,
this approach requires an understanding of the strain distribution and its effect
on band alignment. Here, we study a WSe2-MoS2 lateral heterojunction using
scanning tunnelling microscopy and image its moire pattern to map the full two
dimensional strain tensor with high spatial resolution. Using scanning tunnelling
spectroscopy, we measure both the strain and the band alignment of the WSe2-MoS2
lateral heterojunction. We find that the misfit strain induces type II to type I
band alignment transformation. Scanning transmission electron microscopy reveals
the dislocations at the interface that partially relieve the strain. Finally, we
observe a distinctive electronic structure at the interface due to hetero
bonding.
PMID- 29335570
TI - Machine learning for tracking illegal wildlife trade on social media.
PMID- 29335569
TI - Apparent shift in long-range motion trajectory by local pattern orientation.
AB - The present study shows that the apparent direction of a moving pattern is
systematically affected by its orientation. We found that the perceived direction
of motion of a single Gabor grating changing position in discrete steps
interleaved by blank inter-stimulus interval (ISI) is biased toward the
orientation of the grating. This orientation-induced motion shift peaks for
grating orientations ~+/-15 deg away from the physical motion trajectory and was
profound for relatively short distances. Orientation adaptation revealed that the
directional shift is determined by the apparent -not the physical -orientation of
the grating, and a subsequent experiment demonstrated that directional shift is
also influenced by the orientation of the contrast-defined stimulus envelope.
Results provide further evidence that the apparent trajectory of a motion
stimulus is determined by interactions between motion and pattern information at
relatively high levels of visual processing.
PMID- 29335571
TI - Biodiversity conservation should be a core value of China's Belt and Road
Initiative.
PMID- 29335572
TI - Variation and constraints in hybrid genome formation.
AB - Hybridization is an important source of variation; it transfers adaptive genetic
variation across species boundaries and generates new species. Yet, the limits to
viable hybrid genome formation are poorly understood. Here we investigated to
what extent hybrid genomes are free to evolve by sequencing the genomes of four
island populations of the homoploid hybrid Italian sparrow Passer italiae. We
report that a variety of novel and fully functional hybrid genomic combinations
are likely to have arisen independently on Crete, Corsica, Sicily and Malta, with
differentiation in candidate genes for beak shape and plumage colour. However,
certain genomic regions are invariably inherited from the same parent species,
limiting variation. These regions are over-represented on the Z chromosome and
harbour candidate incompatibility loci, including DNA-repair and mitonuclear
genes. These gene classes may contribute to the general reduction of
introgression on sex chromosomes. This study demonstrates that hybrid genomes may
vary, and identifies new candidate reproductive isolation genes.
PMID- 29335573
TI - Australia's mammal fauna requires a strategic and enhanced network of predator
free havens.
PMID- 29335574
TI - Sexual antagonism and the instability of environmental sex determination.
AB - The sex of an organism can be determined by its genetics or its early
environment. Across the animal kingdom, genetic sex determination (GSD) is far
more common than environmental sex determination (ESD). Here, we propose an
explanation for this pattern: the coupling of genes that bias offspring sex
ratios towards one sex with genes that are beneficial in that sex but costly in
the other. Gradual strengthening of the sex-specific tendency of this association
eventuates in a neo-sex chromosome; that is, GSD. Our model predicts to which
system of heterogamety ESD will evolve when nesting behaviour is an important
determinant of brood sex ratios. It explains the puzzling observation in some GSD
species of sex reversal induced by extreme environments. The model also suggests
an approach to discovering sex-determining genes in ESD species.
PMID- 29335576
TI - Ancient balancing selection on heterocyst function in a cosmopolitan
cyanobacterium.
AB - The conventional view of bacterial adaptation emphasizes the importance of
rapidly evolved changes that are highly repeatable in response to similar
environments and subject to loss in the absence of selection. Consequently,
genetic variation is not expected to persist over long time scales for these
organisms. Here, we show that a geographically widespread gene content
polymorphism has surprisingly been maintained for tens of millions of years of
diversification of the multicellular cyanobacterium Fischerella thermalis. The
polymorphism affects gas permeability of the heterocyst-the oxygen-sensitive,
nitrogen-fixing cell produced by these bacteria-and spatial variation in
temperature favours alternative alleles due to thermodynamic effects on both
heterocyst function and organism fitness at physiological temperature extremes.
Whether or not ancient balancing selection plays a generally important role in
the maintenance of microbial diversity remains to be investigated.
PMID- 29335575
TI - Genotypic variability enhances the reproducibility of an ecological study.
AB - Many scientific disciplines are currently experiencing a 'reproducibility crisis'
because numerous scientific findings cannot be repeated consistently. A novel but
controversial hypothesis postulates that stringent levels of environmental and
biotic standardization in experimental studies reduce reproducibility by
amplifying the impacts of laboratory-specific environmental factors not accounted
for in study designs. A corollary to this hypothesis is that a deliberate
introduction of controlled systematic variability (CSV) in experimental designs
may lead to increased reproducibility. To test this hypothesis, we had 14
European laboratories run a simple microcosm experiment using grass (Brachypodium
distachyon L.) monocultures and grass and legume (Medicago truncatula Gaertn.)
mixtures. Each laboratory introduced environmental and genotypic CSV within and
among replicated microcosms established in either growth chambers (with stringent
control of environmental conditions) or glasshouses (with more variable
environmental conditions). The introduction of genotypic CSV led to 18% lower
among-laboratory variability in growth chambers, indicating increased
reproducibility, but had no significant effect in glasshouses where
reproducibility was generally lower. Environmental CSV had little effect on
reproducibility. Although there are multiple causes for the 'reproducibility
crisis', deliberately including genetic variability may be a simple solution for
increasing the reproducibility of ecological studies performed under stringently
controlled environmental conditions.
PMID- 29335577
TI - Salmonella enterica genomes from victims of a major sixteenth-century epidemic in
Mexico.
AB - Indigenous populations of the Americas experienced high mortality rates during
the early contact period as a result of infectious diseases, many of which were
introduced by Europeans. Most of the pathogenic agents that caused these
outbreaks remain unknown. Through the introduction of a new metagenomic analysis
tool called MALT, applied here to search for traces of ancient pathogen DNA, we
were able to identify Salmonella enterica in individuals buried in an early
contact era epidemic cemetery at Teposcolula-Yucundaa, Oaxaca in southern Mexico.
This cemetery is linked, based on historical and archaeological evidence, to the
1545-1550 CE epidemic that affected large parts of Mexico. Locally, this epidemic
was known as 'cocoliztli', the pathogenic cause of which has been debated for
more than a century. Here, we present genome-wide data from ten individuals for
Salmonella enterica subsp. enterica serovar Paratyphi C, a bacterial cause of
enteric fever. We propose that S. Paratyphi C be considered a strong candidate
for the epidemic population decline during the 1545 cocoliztli outbreak at
Teposcolula-Yucundaa.
PMID- 29335578
TI - Author Correction: The rise and fall of the Old World savannah fauna and the
origins of the African savannah biome.
AB - In the version of this Article originally published, each of the five panels in
Fig. 5 incorrectly contained a black diagonal line across the plot. This has now
been corrected.
PMID- 29335579
TI - The effects of Antibody Engineering CH and CL in Trastuzumab and Pertuzumab
recombinant models: Impact on antibody production and antigen-binding.
AB - Current therapeutic antibodies such as Trastuzumab, are typically of the blood
circulatory IgG1 class (Ckappa/ CHgamma1). Due to the binding to Her2 also
present on normal cell surfaces, side effects such as cardiac failure can
sometimes be associated with such targeted therapy. Using antibody isotype
swapping, it may be possible to reduce systemic circulation through increased
tissue localization, thereby minimising unwanted side effects. However, the
effects of such modifications have yet to be fully characterized, particularly
with regards to their biophysical properties in antigen binding. To do this, we
produced all light and heavy chain human isotypes/subtypes recombinant versions
of Trastuzumab and Pertuzumab, and studied them with respect to recombinant
production and Her2 binding. Our findings show that while the light chain
constant region changes have no major effects on production or Her2 binding, some
heavy chain isotypes, in particularly, IgM and IgD isotypes, can modulate antigen
binding. This study thus provides the groundwork for such isotype modifications
to be performed in the future to yield therapeutics of higher efficacy and
efficiency.
PMID- 29335580
TI - Widespread bone-based fluorescence in chameleons.
AB - Fluorescence is widespread in marine organisms but uncommon in terrestrial
tetrapods. We here show that many chameleon species have bony tubercles
protruding from the skull that are visible through their scales, and fluoresce
under UV light. Tubercles arising from bones of the skull displace all dermal
layers other than a thin, transparent layer of epidermis, creating a 'window'
onto the bone. In the genus Calumma, the number of these tubercles is sexually
dimorphic in most species, suggesting a signalling role, and also strongly
reflects species groups, indicating systematic value of these features. Co-option
of the known fluorescent properties of bone has never before been shown, yet it
is widespread in the chameleons of Madagascar and some African chameleon genera,
particularly in those genera living in forested, humid habitats known to have a
higher relative component of ambient UV light. The fluorescence emits with a
maximum at around 430 nm in blue colour which contrasts well to the green and
brown background reflectance of forest habitats. This discovery opens new avenues
in the study of signalling among chameleons and sexual selection factors driving
ornamentation.
PMID- 29335581
TI - Role of hypoxia in Diffuse Large B-cell Lymphoma: Metabolic repression and
selective translation of HK2 facilitates development of DLBCL.
AB - Published molecular profiling studies in patients with lymphoma suggested the
influence of hypoxia inducible factor-1 alpha (HIF1alpha) targets in prognosis of
DLBCL. Yet, the role of hypoxia in hematological malignancies remains unclear. We
observed that activation of HIF1alpha resulted in global translation repression
during hypoxic stress in DLBCL. Protein translation efficiency as measured using
35S-labeled methionine incorporation revealed a >=50% reduction in translation
upon activation of HIF1alpha. Importantly, translation was not completely
inhibited and expression of clinically correlated hypoxia targets such as GLUT1,
HK2, and CYT-C was found to be refractory to translational repression under
hypoxia in DLBCL cells. Notably, hypoxic induction of these genes was not
observed in normal primary B-cells. Translational repression was coupled with a
decrease in mitochondrial function. Screening of primary DLBCL patient samples
revealed that expression of HK2, which encodes for the enzyme hexokinase 2, was
significantly correlated with DLBCL phenotype. Genetic knockdown studies
demonstrated that HK2 is required for promoting growth of DLBCL under hypoxic
stress. Altogether, our findings provide strong support for the direct
contribution of HK2 in B-cell lymphoma development and suggest that HK2 is a key
metabolic driver of the DLBCL phenotype.
PMID- 29335582
TI - Differential roles of NaV1.2 and NaV1.6 in regulating neuronal excitability at
febrile temperature and distinct contributions to febrile seizures.
AB - Dysregulation of voltage-gated sodium channels (VGSCs) is associated with
multiple clinical disorders, including febrile seizures (FS). The contribution of
different sodium channel subtypes to environmentally triggered seizures is not
well understood. Here we demonstrate that somatic and axonal sodium channels
primarily mediated through NaV1.2 and NaV1.6 subtypes, respectively, behave
differentially at FT, and might play distinct roles in FS generation. In contrast
to sodium channels on the main axonal trunk, somatic ones are more resistant to
inactivation and display significantly augmented currents, faster gating rates
and kinetics of recovery from inactivation at FT, features that promote neuronal
excitabilities. Pharmacological inhibition of NaV1.2 by Phrixotoxin-3 (PTx3)
suppressed FT-induced neuronal hyperexcitability in brain slice, while up
regulation of NaV1.2 as in NaV1.6 knockout mice showed an opposite effect.
Consistently, NaV1.6 knockout mice were more susceptible to FS, exhibiting much
lower temperature threshold and shorter onset latency than wildtype mice. Neuron
modeling further suggests that NaV1.2 is the major subtype mediating FT-induced
neuronal hyperexcitability, and predicts potential outcomes of alterations in
sodium channel subtype composition. Together, these data reveal a role of native
NaV1.2 on neuronal excitability at FT and its important contribution to FS
pathogenesis.
PMID- 29335583
TI - The effect of differentiation and TGFbeta on mitochondrial respiration and
mitochondrial enzyme abundance in cultured primary human skeletal muscle cells.
AB - Measuring mitochondrial respiration in cultured cells is a valuable tool to
investigate the influence of physiological and disease-related factors on
cellular metabolism; however, the details of the experimental workflow greatly
influence the informative value of the results. Working with primary cells and
cell types capable of differentiation can be particularly challenging. We present
a streamlined workflow optimised for investigation of primary human skeletal
muscle cells. We applied the workflow to differentiated and undifferentiated
cells and we investigated the effect of TGFbeta1 treatment. Differentiation of
myoblasts to myotubes increased mitochondrial respiration and abundance of
mitochondrial enzymes and mitochondrial marker proteins. Differentiation also
induced qualitative changes in mitochondrial protein composition and respiration.
TGFbeta1 reduced complex IV protein MTCO1 abundance in both myoblasts and
myotubes. In myoblasts, spare electron transport system (ETS) capacity was
reduced due to a reduction in maximal oxygen consumption. In TGFbeta1-treated
myotubes, the reduction in spare ETS capacity is mainly a consequence of
increased oxidative phosphorylation capacity and complex III protein UQCRC2.
Taken together, our data shows that it is important to monitor muscle cell
differentiation when mitochondrial function is studied. Our workflow is not only
sensitive enough to detect physiological-sized differences, but also adequate to
form mechanistic hypotheses.
PMID- 29335584
TI - Genome-wide identification and characterization of SPL transcription factor
family and their evolution and expression profiling analysis in cotton.
AB - Plant specific transcription factors, SQUAMOSA promoter-binding protein-like
(SPL), are involved in many biological processes. However, no systematical study
has been reported in cotton. In this study, a total of 177 SPL genes were
identified, including 29, 30, 59 and 59 SPLs in Gossypium arboreum, G. raimondii,
G. barbadense, and G. hirsutum, respectively. These SPL genes were classified
into eight phylogenetical groups. The gene structure, conserved motif, and
clustering were highly conserved within each orthologs. Two zinc finger-like
structures (Cys3His and Cys2HisCys) and NLS segments were existed in all GrSPLs.
Segmental duplications play important roles in SPL family expansion, with 20
genes involved in segmental duplications and 2 in tandem duplications, and ten
ortholog pairs in syntenic regions between G. raimondii and A. thaliana. Several
putative cis-elements, involved in light, stresses and phytohormones response,
were found in the promoter regions of GhSPLs, suggesting that plant responses to
those environmental changes may be induced through targeting SPL transcription
factors. RNA-seq analysis shows that SPL genes were differentially expressed in
cotton; some were highly expressed during fiber initiation and early development.
Comparing with other plants, SPL genes show subfunctionalization, lost and/or
gain functions in cotton during long-term domestication and evolution.
PMID- 29335586
TI - Publisher Correction: Pelagic barite precipitation at micromolar ambient sulfate.
AB - The original version of this Article contained an error in the barite saturation
state equation in the fourth paragraph of the Introduction and incorrectly read
'Omegabarite=({134Ba2+}?{SO42-})/Ksp)'. The correct version removes the
superscript 134 next to 'Ba2+'. This error has now been corrected in both the PDF
and HTML versions of the Article.
PMID- 29335585
TI - Robust fabrication of thin film polyamide-TiO2 nanocomposite membranes with
enhanced thermal stability and anti-biofouling propensity.
AB - The development of nano-enabled composite materials has led to a paradigm shift
in the manufacture of high-performance nanocomposite membranes with enhanced
permeation, thermo-mechanical, and antibacterial properties. The major challenges
to the successful incorporation of nanoparticles (NPs) to polymer films are the
severe aggregation of the NPs and the weak compatibility of NPs with polymers.
These two phenomena lead to the formation of non-selective voids at the interface
of the polymer and NPs, which adversely affect the separation performance of the
membrane. To overcome these challenges, we have developed a new method for the
fabrication of robust TFN reverse osmosis membranes. This approach relies on the
simultaneous synthesis and surface functionalization of TiO2 NPs in an organic
solvent (heptane) via biphasic solvothermal reaction. The resulting stable
suspension of the TiO2 NPs in heptane was then utilized in the interfacial (in
situ) polymerization reaction where the NPs were entrapped within the matrix of
the polyamide (PA) membrane. TiO2 NPs of 10 nm were effectively incorporated into
the thin PA layer and improved the thermal stability and anti-biofouling
properties of the resulting TFN membranes. These features make our synthesized
membranes potential candidates for applications where the treatment of high
temperature streams containing biomaterials is desirable.
PMID- 29335587
TI - Bacterial and Fungal Community Composition and Functional Activity Associated
with Lake Wetland Water Level Gradients.
AB - The water regime is often the primary force driving the evolution of freshwater
lakes, but how soil microbes responded to this process is far from understood.
This study sampled wetland soils from a shallow lake that experienced water
regime changes, Poyang Lake of China, to explore the features of bacterial and
fungal community in response to water level changes. The soil physicochemical
properties, T-RFLP based community structures and soil activities (including
basal respiration, microbial biomass and enzymes) were all determined. Soil
microbial eco-function was captured by testing the carbon metabolism with Biolog
Ecoplate. The results showed remarkable influence of the water level gradients on
the soil physicochemical properties, microbial community structures and soil
activities. However, the carbon utilization profile exhibited weak connections
with the environmental variables and microbial community structures (p > 0.05).
The microbial activities were significantly correlated with both bacterial and
fungal community structures. Our results also emphasized the ascendant role of
the deterministic process in the assemblages of microbial community structures
and functions in wetland. In conclusion, this study revealed the discrepancy
between community structures and eco-functions in response to water level
gradients, and a relatively stable eco-function helped to maintain the ecosystem
function of wetland from a long-term perspective.
PMID- 29335589
TI - Strong modulation of second-harmonic generation with very large contrast in
semiconducting CdS via high-field domain.
AB - Dynamic control of nonlinear signals is critical for a wide variety of
optoelectronic applications, such as signal processing for optical computing.
However, controlling nonlinear optical signals with large modulation strengths
and near-perfect contrast remains a challenging problem due to intrinsic second
order nonlinear coefficients via bulk or surface contributions. Here, via
electrical control, we turn on and tune second-order nonlinear coefficients in
semiconducting CdS nanobelts from zero to up to 151 pm V-1, a value higher than
other intrinsic nonlinear coefficients in CdS. We also observe ultrahigh ON/OFF
ratio of >104 and modulation strengths ~200% V-1 of the nonlinear signal. The
unusual nonlinear behavior, including super-quadratic voltage and power
dependence, is ascribed to the high-field domain, which can be further controlled
by near-infrared optical excitation and electrical gating. The ability to
electrically control nonlinear optical signals in nanostructures can enable
optoelectronic devices such as optical transistors and modulators for on-chip
integrated photonics.
PMID- 29335588
TI - Peripheral iron levels in children with attention-deficit hyperactivity disorder:
a systematic review and meta-analysis.
AB - There is growing recognition that the risk of attention-deficit hyperactivity
disorder (ADHD) in children may be influenced by micronutrient deficiencies,
including iron. We conducted this meta-analysis to examine the association
between ADHD and iron levels/iron deficiency (ID). We searched for the databases
of the PubMed, ScienceDirect, Cochrane CENTRAL, and ClinicalTrials.gov up to
August 9th, 2017. Primary outcomes were differences in peripheral iron levels in
children with ADHD versus healthy controls (HCs) and the severity of ADHD
symptoms in children with/without ID (Hedges' g) and the pooled adjusted odds
ratio (OR) of the association between ADHD and ID. Overall, seventeen articles
met the inclusion criteria. Peripheral serum ferritin levels were significantly
lower in ADHD children (children with ADHD = 1560, HCs = 4691, Hedges' g =
0.246, p = 0.013), but no significant difference in serum iron or transferrin
levels. In addition, the severity of ADHD was significantly higher in the
children with ID than those without ID (with ID = 79, without ID = 76, Hedges' g
= 0.888, p = 0.002), and there was a significant association between ADHD and ID
(OR = 1.636, p = 0.031). Our results suggest that ADHD is associated with lower
serum ferritin levels and ID. Future longitudinal studies are required to confirm
these associations and to elucidate potential mechanisms.
PMID- 29335590
TI - Direct observation of the effects of cellulose synthesis inhibitors using live
cell imaging of Cellulose Synthase (CESA) in Physcomitrella patens.
AB - Results from live cell imaging of fluorescently tagged Cellulose Synthase (CESA)
proteins in Cellulose Synthesis Complexes (CSCs) have enhanced our understanding
of cellulose biosynthesis, including the mechanisms of action of cellulose
synthesis inhibitors. However, this method has been applied only in Arabidopsis
thaliana and Brachypodium distachyon thus far. Results from freeze fracture
electron microscopy of protonemal filaments of the moss Funaria hygrometrica
indicate that a cellulose synthesis inhibitor, 2,6-dichlorobenzonitrile (DCB),
fragments CSCs and clears them from the plasma membrane. This differs from
Arabidopsis, in which DCB causes CSC accumulation in the plasma membrane and a
different cellulose synthesis inhibitor, isoxaben, clears CSCs from the plasma
membrane. In this study, live cell imaging of the moss Physcomitrella patens
indicated that DCB and isoxaben have little effect on protonemal growth rates,
and that only DCB causes tip rupture. Live cell imaging of mEGFP-PpCESA5 and
mEGFP-PpCESA8 showed that DCB and isoxaben substantially reduced CSC movement,
but had no measureable effect on CSC density in the plasma membrane. These
results suggest that DCB and isoxaben have similar effects on CSC movement in P.
patens and Arabidopsis, but have different effects on CSC intracellular
trafficking, cell growth and cell integrity in these divergent plant lineages.
PMID- 29335591
TI - Functionalized Sugarcane Bagasse for U(VI) Adsorption from Acid and Alkaline
Conditions.
AB - The highly efficient removal of uranium from mine tailings effluent, radioactive
wastewater and enrichment from seawater is of great significance for the
development of nuclear industry. In this work, we prepared an efficient U(VI)
adsorbent by EDTA modified sugarcane bagasse (MESB) with a simple process. The
prepared adsorbent preserves high adsorptive capacity for UO22+ (pH 3.0) and
uranyl complexes, such as UO2(OH)+, (UO2)2(OH)22+ and (UO2)3(OH)5+ (pH 4.0 and pH
5.0) and good repeatability in acidic environment. The maximum adsorption
capacity for U(VI) at pH 3.0, 4.0 and 5.0 is 578.0, 925.9 and 1394.1 mg/g and the
adsorption capacity loss is only 7% after five cycles. With the pH from 3.0 to
5.0, the inhibitive effects of Na+ and K+ decreased but increased of Mg2+ and
Ca2+. MESB also exhibits good adsorption for [UO2(CO3)3]4- at pH 8.3 from 10 mg/L
to 3.3 MUg/L. Moreover, MESB could effectively extract U(VI) from simulated
seawater in the presence of other metals ions. This work provided a general and
efficient uranyl enriched material for nuclear industry.
PMID- 29335592
TI - Differential tolerance to nickel between Dreissena polymorpha and Dreissena
rostriformis bugensis populations.
AB - Differential tolerance to stress is partly responsible for the heterogeneity of
biomarker responses between populations of a sentinel species. Although currently
used for freshwater biomonitoring, studies concerning inter-populational
variability in tolerance to contaminants for the zebra mussel (Dreissena
polymorpha) are scarce. Moreover, this well-known invader is currently replaced
by another, the quagga mussel (Dreissena rostriformis bugensis). To evaluate the
differential tolerance between dreissenids, several populations of both species
were exposed to a high concentration of nickel. A LT50 (time when 50% of
individuals were dead) was established for each population. Biomarker responses
and internal nickel concentration were also measured, to link tolerance with
physiological status. Results evidenced that D. polymorpha populations are more
heterogeneous and more tolerant than D. r. bugensis ones. For D. polymorpha
populations only, LT50 values were positively correlated with the nickel
contamination in situ, with higher anti-oxidative defences and a higher
Integrated Biomarker Response value in the field. Such findings may be explained
by local adaptation and invasion dynamic within each species. The significance of
this differential tolerance when using biomarker responses for biomonitoring
purposes is thus discussed.
PMID- 29335593
TI - Bacterial iron reduction and biogenic mineral formation for the stabilisation of
corroded iron objects.
AB - Exploiting bacterial metabolism for the stabilisation of corroded iron artefacts
is a promising alternative to conventional conservation-restoration methods.
Bacterial iron reduction coupled to biogenic mineral formation has been shown to
promote the conversion of reactive into stable corrosion products that are
integrated into the natural corrosion layer of the object. However, in order to
stabilise iron corrosion, the formation of specific biogenic minerals is
essential. In this study, we used the facultative anaerobe Shewanella loihica for
the production of stable biogenic iron minerals under controlled chemical
conditions. The biogenic formation of crystalline iron phosphates was observed
after iron reduction in a solution containing Fe(III) citrate. When the same
biological treatment was applied on corroded iron plates, a layer composed of
iron phosphates and iron carbonates was formed. Surface and cross-section
analyses demonstrated that these two stable corrosion products replaced 81% of
the reactive corrosion layer after two weeks of treatment. Such results
demonstrate the potential of a biological treatment in the development of a
stabilisation method to preserve corroded iron objects.
PMID- 29335594
TI - Interfacial Coupling Effect on Electron Transport in MoS2/SrTiO3 Heterostructure:
An Ab-initio Study.
AB - A variety of theoretical and experimental works have reported several potential
applications of MoS2 monolayer based heterostructures (HSs) such as light
emitting diodes, photodetectors and field effect transistors etc. In the present
work, we have theoretically performed as a model case study, MoS2 monolayer
deposited over insulating SrTiO3 (001) to study the band alignment at TiO2
termination. The interfacial characteristics are found to be highly dependent on
the interface termination. With an insulating oxide material, a significant band
gap (0.85eV) is found in MoS2/TiO2 interface heterostructure (HS). A unique
electronic band profile with an indirect band gap (0.67eV) is observed in MoS2
monolayer when confined in a cubic environment of SrTiO3 (STO). Adsorption
analysis showed the chemisorption of MoS2 on the surface of STO substrate with
TiO2 termination which is justified by the charge density calculations that shows
the existence of covalent bonding at the interface. The fabrication of HS of such
materials paves the path for developing the unprecedented 2D materials with
exciting properties such as semiconducting devices, thermoelectric and
optoelectronic applications.
PMID- 29335595
TI - Mapping the epidemic changes and risks of hemorrhagic fever with renal syndrome
in Shaanxi Province, China, 2005-2016.
AB - Hemorrhagic fever with renal syndrome (HFRS) is a major rodent-borne zoonosis.
Each year worldwide, 60,000-100,000 HFRS human cases are reported in more than
seventy countries with almost 90% these cases occurring in China. Shaanxi
Province in China has been among the most seriously affected areas since 1955.
During 2009-2013, Shaanxi reported 11,400 human cases, the most of all provinces
in China. Furthermore, the epidemiological features of HFRS have changed over
time. Using long-term data of HFRS from 2005 to 2016, we carried out this
retrospective epidemiological study combining ecological assessment models in
Shaanxi. We found the majority of HFRS cases were male farmers who acquired
infection in Guanzhong Plain, but the geographic extent of the epidemic has
slowly spread northward. The highest age-specific attack rate since 2011 was
among people aged 60-74 years, and the percentage of HFRS cases among the elderly
increased from 12% in 2005 to 25% in 2016. We highly recommend expanding HFRS
vaccination to people older than 60 years to better protect against the disease.
Multivariate analysis revealed artificial area, cropland, pig and population
density, GDP, and climate conditions (relative humidity, precipitation, and wind
speed) as significant risk factors in the distribution of HFRS.
PMID- 29335596
TI - Circulating microRNA signature for the diagnosis of childhood dilated
cardiomyopathy.
AB - Circulating miRNAs are proposed as a biomarker of heart disease. This study
evaluated whether circulating miRNAs could be used as a biomarker for childhood
dilated cardiomyopathy (CDCM). A total of 28 participants were enrolled in a
discovery set, including patients with CDCM (n = 16) and healthy children (n =
12). The cardiac function of patients with CDCM was characterized by
echocardiography and serum miRNA profiles of all participants were assessed by
miRNA sequencing. After miRNA profiling, we quantitatively confirmed 148
regulated miRNAs in patients with CDCM compared with healthy subjects, and none
were downregulated. Validation of candidate miRNAs was assessed by quantitative
real-time polymerase chain reaction in other patients with CDCM (n = 30) and
healthy controls (n = 16). A unique signature comprising mir-142-5p, mir-143-3p,
mir-27b-3p, and mir-126-3p differentiated patients with CDCM from healthy
subjects. Importantly, we observed an increase in mir-126-3p or let-7g in
parallel with a robust decrease in the ejection fraction in patients with CDCM,
which could differentiate heart failure patients from non-heart failure patients
with CDCM. Moreover, mir-126-3p and let-7g were significantly negatively
associated with the left ventricular ejection fraction. This study shows that a
signature of four serum miRNAs may be a potential biomarker for diagnosing CDCM
and assessing heart failure.
PMID- 29335597
TI - Exercise Protects Against Olanzapine-Induced Hyperglycemia in Male C57BL/6J Mice.
AB - Olanzapine is a widely prescribed antipsychotic drug. While effective in reducing
psychoses, treatment with olanzapine causes rapid increases in blood glucose. We
wanted to determine if a single bout of exercise, immediately prior to treatment,
would attenuate the olanzapine-induced rise in blood glucose and if this occurred
in an IL-6 dependent manner. We found that exhaustive, but not moderate exercise,
immediately prior to treatment, prevented olanzapine-induced hyperglycemia and
this occurred in parallel with increases in serum IL-6. To determine if IL-6 was
involved in the mechanisms through which exhaustive exercise protected against
olanzapine-induced hyperglycemia several additional experiments were completed.
Treatment with IL-6 (3 ng/g bw, IP) alone did not protect against olanzapine
induced increases in blood glucose. The protective effects of exhaustive exercise
against olanzapine-induced increases in blood glucose were intact in whole body
IL-6 knockout mice. Similarly, treating mice with an IL-6 neutralizing antibody
prior to exhaustive exercise did not negate the protective effect of exercise
against olanzapine-induced hyperglycemia. Our findings provide evidence that a
single bout of exhaustive exercise protects against acute olanzapine-induced
hyperglycemia and that IL-6 is neither sufficient, nor required for exercise to
protect against increases in blood glucose with olanzapine treatment.
PMID- 29335598
TI - Gene and MicroRNA Perturbations of Cellular Response to Pemetrexed Implicate
Biological Networks and Enable Imputation of Response in Lung Adenocarcinoma.
AB - Pemetrexed is indicated for non-small cell lung carcinoma and mesothelioma, but
often has limited efficacy due to drug resistance. To probe the molecular
mechanisms underlying chemotherapeutic response, we performed mRNA and microRNA
(miRNA) expression profiling of pemetrexed treated and untreated lymphoblastoid
cell lines (LCLs) and applied a hierarchical Bayesian method. We identified
genetic variation associated with gene expression in human lung tissue for the
most significant differentially expressed genes (Benjamini-Hochberg [BH] adjusted
p < 0.05) using the Genotype-Tissue Expression data and found evidence for their
clinical relevance using integrated molecular profiling and lung adenocarcinoma
survival data from The Cancer Genome Atlas project. We identified 39 miRNAs with
significant differential expression (BH adjusted p < 0.05) in LCLs. We developed
a gene expression based imputation model of drug sensitivity, quantified its
prediction performance, and found a significant correlation of the imputed
phenotype generated from expression data with survival time in lung
adenocarcinoma patients. Differentially expressed genes (MTHFD2 and SUFU) that
are putative targets of differentially expressed miRNAs also showed differential
perturbation in A549 fusion lung tumor cells with further replication in A549
cells. Our study suggests pemetrexed may be used in combination with agents that
target miRNAs to increase its cytotoxicity.
PMID- 29335599
TI - Hindlimb Ischemia Impairs Endothelial Recovery and Increases Neointimal
Proliferation in the Carotid Artery.
AB - Peripheral ischemia is associated with higher degree of endothelial dysfunction
and a worse prognosis after percutaneous coronary interventions (PCI). However,
the role of peripheral ischemia on vascular remodeling in remote districts
remains poorly understood. Here we show that the presence of hindlimb ischemia
significantly enhances neointima formation and impairs endothelial recovery in
balloon-injured carotid arteries. Endothelial-derived microRNAs are involved in
the modulation of these processes. Indeed, endothelial miR-16 is remarkably
upregulated after vascular injury in the presences of hindlimb ischemia and
exerts a negative effect on endothelial repair through the inhibition of
RhoGDIalpha and nitric oxide (NO) production. We showed that the repression of
RhoGDIalpha by means of miR-16 induces RhoA, with consequent reduction of NO
bioavailability. Thus, hindlimb ischemia affects negative carotid remodeling
increasing neointima formation after injury, while systemic antagonizzation of
miR-16 is able to prevent these negative effects.
PMID- 29335600
TI - Alteration in Fluidity of Cell Plasma Membrane in Huntington Disease Revealed by
Spectral Phasor Analysis.
AB - Huntington disease (HD) is a late-onset genetic neurodegenerative disorder caused
by expansion of cytosine-adenine-guanine (CAG) trinucleotide in the exon 1 of the
gene encoding the polyglutamine (polyQ). It has been shown that protein
degradation and lipid metabolism is altered in HD. In many neurodegenerative
disorders, impaired lipid homeostasis is one of the early events in the disease
onset. Yet, little is known about how mutant huntingtin may affect phospholipids
membrane fluidity. Here, we investigated how membrane fluidity in the living
cells (differentiated PC12 and HEK293 cell lines) are affected using a
hyperspectral imaging of widely used probes, LAURDAN. Using phasor approach, we
characterized the fluorescence of LAURDAN that is sensitive to the polarity of
the immediate environment. LAURDAN is affected by the physical order of
phospholipids (lipid order) and reports the membrane fluidity. We also validated
our results using a different fluorescent membrane probe, Nile Red (NR). The
plasma membrane in the cells expressing expanded polyQ shows a shift toward
increased membrane fluidity revealed by both LAURDAN and NR spectral phasors.
This finding brings a new perspective in the understanding of the early stages of
HD that can be used as a target for drug screening.
PMID- 29335602
TI - In situ single-shot diffractive fluence mapping for X-ray free-electron laser
pulses.
AB - Free-electron lasers (FELs) in the extreme ultraviolet (XUV) and X-ray regime
opened up the possibility for experiments at high power densities, in particular
allowing for fluence-dependent absorption and scattering experiments to reveal
non-linear light-matter interactions at ever shorter wavelengths. Findings of
such non-linear effects are met with tremendous interest, but prove difficult to
understand and model due to the inherent shot-to-shot fluctuations in photon
intensity and the often structured, non-Gaussian spatial intensity profile of a
focused FEL beam. Presently, the focused beam is characterized and optimized
separately from the actual experiment. Here, we present the simultaneous
measurement of XUV diffraction signals from solid samples in tandem with the
corresponding single-shot spatial fluence distribution on the actual sample. Our
in situ characterization scheme enables direct monitoring of the sample
illumination, providing a basis to optimize and quantitatively understand FEL
experiments.
PMID- 29335601
TI - Loss of CD14 leads to disturbed epithelial-B cell crosstalk and impairment of the
intestinal barrier after E. coli Nissle monoassociation.
AB - The TLR4 co-receptor CD14 was identified as an IBD candidate gene. Here, its
influence on the intestinal barrier was addressed utilizing E. coli Nissle (EcN),
which induces severe inflammation in germfree TLR4-/- mice. After
monoassociation, EcN was detected in spleens and livers of TLR4-/- and CD14-/-
but not wildtype mice. Barrier impairment was characterized by increased
apoptosis and decreased epithelial junction (EJ) expression and was reversed by
TLR2 stimulation in CD14-/- mice. Bone marrow (BM) transplantation revealed
contribution of hematopoietic and non-hematopoietic cells towards intestinal
homeostasis. EcN inoculated WT mice showed B cell activation, CD14-/- and TLR4-/-
mice cytotoxic T cell and impaired B cell responses. The latter was characterized
by absence of B cells in TLR4-/- mice, decreased levels of EcN induced
immunoglobulins and downregulation of their transporter pIgR. EcN colonization of
mice with genetically or antibody induced impaired B cell response resulted in
dissemination of EcN and downregulation of EJ. BM chimeras indicated that CD14
originating from radiation resistant cells is sufficient to restore EJ-function.
Overall, CD14/TLR4 signalling seems to be critical for intestinal barrier
function and for the crosstalk between B cells and the epithelium, underlining
that CD14 serves as a protective modulator of intestinal homeostasis.
PMID- 29335603
TI - In vivo simultaneous transcriptional activation of multiple genes in the brain
using CRISPR-dCas9-activator transgenic mice.
AB - Despite rapid progresses in the genome-editing field, in vivo simultaneous
overexpression of multiple genes remains challenging. We generated a transgenic
mouse using an improved dCas9 system that enables simultaneous and precise in
vivo transcriptional activation of multiple genes and long noncoding RNAs in the
nervous system. As proof of concept, we were able to use targeted activation of
endogenous neurogenic genes in these transgenic mice to directly and efficiently
convert astrocytes into functional neurons in vivo. This system provides a
flexible and rapid screening platform for studying complex gene networks and gain
of-function phenotypes in the mammalian brain.
PMID- 29335604
TI - Dentate network activity is necessary for spatial working memory by supporting
CA3 sharp-wave ripple generation and prospective firing of CA3 neurons.
AB - Complex spatial working memory tasks have been shown to require both hippocampal
sharp-wave ripple (SWR) activity and dentate gyrus (DG) neuronal activity. We
therefore asked whether DG inputs to CA3 contribute to spatial working memory by
promoting SWR generation. Recordings from DG and CA3 while rats performed a
dentate-dependent working memory task on an eight-arm radial maze revealed that
the activity of dentate neurons and the incidence rate of SWRs both increased
during reward consumption. We then found reduced reward-related CA3 SWR
generation without direct input from dentate granule neurons. Furthermore, CA3
cells with place fields in not-yet-visited arms preferentially fired during SWRs
at reward locations, and these prospective CA3 firing patterns were more
pronounced for correct trials and were dentate-dependent. These results indicate
that coordination of CA3 neuronal activity patterns by DG is necessary for the
generation of neuronal firing patterns that support goal-directed behavior and
memory.
PMID- 29335606
TI - Conserved properties of dentate gyrus neurogenesis across postnatal development
revealed by single-cell RNA sequencing.
AB - The dentate gyrus of the hippocampus is a brain region in which neurogenesis
persists into adulthood; however, the relationship between developmental and
adult dentate gyrus neurogenesis has not been examined in detail. Here we used
single-cell RNA sequencing to reveal the molecular dynamics and diversity of
dentate gyrus cell types in perinatal, juvenile, and adult mice. We found
distinct quiescent and proliferating progenitor cell types, linked by transient
intermediate states to neuroblast stages and fully mature granule cells. We
observed shifts in the molecular identity of quiescent and proliferating radial
glia and granule cells during the postnatal period that were then maintained
through adult stages. In contrast, intermediate progenitor cells, neuroblasts,
and immature granule cells were nearly indistinguishable at all ages. These
findings demonstrate the fundamental similarity of postnatal and adult
neurogenesis in the hippocampus and pinpoint the early postnatal transformation
of radial glia from embryonic progenitors to adult quiescent stem cells.
PMID- 29335605
TI - Dietary salt promotes neurovascular and cognitive dysfunction through a gut
initiated TH17 response.
AB - A diet rich in salt is linked to an increased risk of cerebrovascular diseases
and dementia, but it remains unclear how dietary salt harms the brain. We report
that, in mice, excess dietary salt suppresses resting cerebral blood flow and
endothelial function, leading to cognitive impairment. The effect depends on
expansion of TH17 cells in the small intestine, resulting in a marked increase in
plasma interleukin-17 (IL-17). Circulating IL-17, in turn, promotes endothelial
dysfunction and cognitive impairment by the Rho kinase-dependent inhibitory
phosphorylation of endothelial nitric oxide synthase and reduced nitric oxide
production in cerebral endothelial cells. The findings reveal a new gut-brain
axis linking dietary habits to cognitive impairment through a gut-initiated
adaptive immune response compromising brain function via circulating IL-17. Thus,
the TH17 cell-IL-17 pathway is a putative target to counter the deleterious brain
effects induced by dietary salt and other diseases associated with TH17
polarization.
PMID- 29335607
TI - Grid scale drives the scale and long-term stability of place maps.
AB - Medial entorhinal cortex (MEC) grid cells fire at regular spatial intervals and
project to the hippocampus, where place cells are active in spatially restricted
locations. One feature of the grid population is the increase in grid spatial
scale along the dorsal-ventral MEC axis. However, the difficulty in perturbing
grid scale without impacting the properties of other functionally defined MEC
cell types has obscured how grid scale influences hippocampal coding and spatial
memory. Here we use a targeted viral approach to knock out HCN1 channels
selectively in MEC, causing the grid scale to expand while leaving other MEC
spatial and velocity signals intact. Grid scale expansion resulted in place scale
expansion in fields located far from environmental boundaries, reduced long-term
place field stability and impaired spatial learning. These observations, combined
with simulations of a grid-to-place cell model and position decoding of place
cells, illuminate how grid scale impacts place coding and spatial memory.
PMID- 29335608
TI - N6-methyladenosine RNA modification regulates embryonic neural stem cell self
renewal through histone modifications.
AB - Internal N6-methyladenosine (m6A) modification is widespread in messenger RNAs
(mRNAs) and is catalyzed by heterodimers of methyltransferase-like protein 3
(Mettl3) and Mettl14. To understand the role of m6A in development, we deleted
Mettl14 in embryonic neural stem cells (NSCs) in a mouse model. Phenotypically,
NSCs lacking Mettl14 displayed markedly decreased proliferation and premature
differentiation, suggesting that m6A modification enhances NSC self-renewal.
Decreases in the NSC pool led to a decreased number of late-born neurons during
cortical neurogenesis. Mechanistically, we discovered a genome-wide increase in
specific histone modifications in Mettl14 knockout versus control NSCs. These
changes correlated with altered gene expression and observed cellular phenotypes,
suggesting functional significance of altered histone modifications in knockout
cells. Finally, we found that m6A regulates histone modification in part by
destabilizing transcripts that encode histone-modifying enzymes. Our results
suggest an essential role for m6A in development and reveal m6A-regulated histone
modifications as a previously unknown mechanism of gene regulation in mammalian
cells.
PMID- 29335610
TI - Liquid-like thermal conduction in intercalated layered crystalline solids.
AB - As a generic property, all substances transfer heat through microscopic
collisions of constituent particles 1 . A solid conducts heat through both
transverse and longitudinal acoustic phonons, but a liquid employs only
longitudinal vibrations2,3. As a result, a solid is usually thermally more
conductive than a liquid. In canonical viewpoints, such a difference also serves
as the dynamic signature distinguishing a solid from a liquid. Here, we report
liquid-like thermal conduction observed in the crystalline AgCrSe2. The
transverse acoustic phonons are completely suppressed by the ultrafast dynamic
disorder while the longitudinal acoustic phonons are strongly scattered but
survive, and are thus responsible for the intrinsically ultralow thermal
conductivity. This scenario is applicable to a wide variety of layered compounds
with heavy intercalants in the van der Waals gaps, manifesting a broad
implication on suppressing thermal conduction. These microscopic insights might
reshape the fundamental understanding on thermal transport properties of matter
and open up a general opportunity to optimize performances of thermoelectrics.
PMID- 29335611
TI - Designing perturbative metamaterials from discrete models.
AB - Identifying material geometries that lead to metamaterials with desired
functionalities presents a challenge for the field. Discrete, or reduced-order,
models provide a concise description of complex phenomena, such as negative
refraction, or topological surface states; therefore, the combination of
geometric building blocks to replicate discrete models presenting the desired
features represents a promising approach. However, there is no reliable way to
solve such an inverse problem. Here, we introduce 'perturbative metamaterials', a
class of metamaterials consisting of weakly interacting unit cells. The weak
interaction allows us to associate each element of the discrete model with
individual geometric features of the metamaterial, thereby enabling a systematic
design process. We demonstrate our approach by designing two-dimensional elastic
metamaterials that realize Veselago lenses, zero-dispersion bands and topological
surface phonons. While our selected examples are within the mechanical domain,
the same design principle can be applied to acoustic, thermal and photonic
metamaterials composed of weakly interacting unit cells.
PMID- 29335609
TI - Prognostic significance of HALP (hemoglobin, albumin, lymphocyte and platelet) in
patients with bladder cancer after radical cystectomy.
AB - The outcome of bladder cancer after radical cystectomy is heterogeneous. We aim
to evaluate the prognostic value of HALP (hemoglobin, albumin, lymphocyte and
platelet) and explore novel prognostic indexes for patients with bladder cancer
after radical cystectomy. In this retrospective study, 516 patients with bladder
cancer after radical cystectomy were included. The median follow-up was 37 months
(2 to 99 mo). Risk factors of decreased overall survival were older age, high TNM
stage, high American Society of Anesthesiologists (ASA) grade and low HALP score.
The predictive accuracy was better with HALP-based nomogram than TNM stage (C-
index 0.76 +/- 0.039 vs. 0.708 +/- 0.041). By combining ASA grade and HALP, we
created a novel index-HALPA score and found it an independent risk factor for
decreased survival (HALPA score = 1, HR 1.624, 95% CI 1.139-2.314, P = 0.007;
HALPA score = 2, HR 3.471, 95% CI: 1.861-6.472, P < 0.001).The present study
identified the prognostic value of HALP and provided a novel index HALPA score
for bladder cancer after radical cystectomy.
PMID- 29335612
TI - Wrist circumference is associated with increased systolic blood pressure in
children with overweight/obesity.
AB - Wrist circumference is a clinical marker for insulin-resistance in
overweight/obese children and adolescents. Insulin resistance is considered a
major determinant of increased vascular resistance and hypertension. The aim of
the study was to investigate the association between wrist circumference and
systolic (S) and diastolic (D) blood pressure (BP) in a population of
overweight/obese children and adolescents. A population of 1133 overweight/obese
children and adolescents (n = 1133) were consecutively enrolled. Multivariate
regression analyses were used to investigate the influence of independent
variables on the variance of BP. The prevalence of hypertension was 21.74% in
males and 28.95% in females (p = 0.048). The results showed that SBP was
significantly associated with wrist circumference in both genders (p < 0.0001 for
both comparisons). We found no association between DBP and wrist circumference in
either gender. Wrist circumference accounted for 17% of the total variance of SBP
in males and 14% in females. Wrist circumference, a marker of insulin resistance,
is associated with increased SBP in overweight/obese children and adolescents,
suggesting a role of insulin resistance in the pathogenesis and development of
hypertension.
PMID- 29335613
TI - Food items contributing to high dietary salt intake among Japanese adults in the
2012 National Health and Nutrition Survey.
PMID- 29335614
TI - Reliability of pulse waveform separation analysis responses to an orthostatic
challenge.
AB - Cardiovascular autonomic nervous system function can be assessed using an
orthostatic challenge to induce arterial wave reflection. While arterial
reflection is typically estimated using a central augmentation index, a superior
estimation can be obtained using pulse wave separation analysis to estimate the
aortic backward pressure wave (Pb). However, to be of value in a clinical or
research setting, an assessment tool must be precise (reliable). Therefore, this
study sought to determine the measurement precision of Pb responses to a modified
tilt-table test. Twenty healthy adults (26.4 year (SD 5.2), 24.7 kg/m2 (SD 3.8),
55% female) were tested in a fasted state on three different mornings separated
by a maximum of seven days. Pressure waveforms were recorded on the left arm, and
aortic waveforms were generated using a generalized transfer function.
Subsequently, a physiologic flow waveform was assumed to separate the aortic
pressure wave into its forward and timing-independent backward (Pb) components.
The criterion intra-class correlation coefficient of >=0.75 was exceeded at
baseline (0.79), following a 5-min tilt (0.75), and following a 5-min recovery
from tilt (0.75). The standard error of measurement was 7%. These findings
indicate that in a healthy cohort, the Pb response to an orthostatic challenge
can be assessed with acceptable precision. The next step is to determine the
sensitivity (validity) of this technique in identifying cardiovascular autonomic
dysfunction in patient groups.
PMID- 29335615
TI - Marinobufagenin is related to elevated central and 24-h systolic blood pressures
in young black women: the African-PREDICT Study.
AB - Marinobufagenin (MBG) is an endogenous steroidal alpha1-Na+K+-ATPase inhibitor.
Because of its role in sodium handling, MBG has been associated with both
antihypertensive and prohypertensive effects in normal physiology and pathology.
MBG is positively associated with blood pressure in Dahl salt-sensitive rats
exhibiting a similar hypertensive phenotype to black populations, characterized
by impaired urinary Na+ excretion. However, clinical studies exploring blood
pressure (BP)-related effects of MBG in black populations are scant. We
determined whether the MBG/Na+ ratio (assessing the effectiveness of Na+
excretion resistance to MBG) is related to systolic BP (SBP) in young black men
and women, compared to whites. We included 331 apparently healthy participants
(20-30 years) (42.9% black, 43.8% men) on a habitual diet. We obtained 24-h and
central SBP, and 24-h urinary Na+ and MBG levels. We found no ethnic differences
in MBG, Na+ or MBG/Na+. MBG excretion correlated positively with Na+ excretion in
all groups and to SBP in white men and black women (p <= 0.011). In black women
only SBP related positively to MBG/Na+ in single and multi-variable adjusted
regression models: central SBP (R2 = 0.26; beta = 0.28; p = 0.039), 24-h SBP (R2
= 0.46; beta = 0.30; p = 0.011), daytime (R2 = 0.38; beta = 0.28; p = 0.023) and
nighttime SBP (R2 = 0.38; beta = 0.33; p = 0.009). In contrast, inverse
associations of MBG/Na+ with nighttime SBP were evident in white women (r =
0.20; p = 0.038) but lost significance after multiple adjustments (R2 = 0.36;
beta = -0.13; p = 0.12). We found independent positive associations of SBP with
MBG/Na+ in black women. This data supports the concept that reduced MBG-mediated
Na+ excretion can contribute to adverse hemodynamics.
PMID- 29335616
TI - Roles of angiotensin II type 2 receptor in mice with fetal growth restriction.
AB - Our previous report indicated that vascular injury enhances vascular remodeling
in fetal growth restriction (FGR) mice. The angiotensin II type 2 receptor (AT2R)
is relatively highly expressed in fetal mice. Therefore, we investigated the
roles of AT2R in FGR-induced cardiovascular disease using AT2R knockout (AT2KO)
mice. Dams (wild-type and AT2KO mice) were fed an isocaloric diet containing 20%
protein (NP) or 8% protein (LP) until delivery. Arterial blood pressure, body
weight, and histological changes in organs were investigated in offspring. The
birth weight of offspring from dams fed an LP diet (LPO) was significantly lower
than that of offspring from dams fed an NP diet. The heart/body and kidney/body
weight ratios in AT2KO-LPO at 12 weeks of age were significantly higher than
those in the other groups. Greater thickness of the left ventricular wall, larger
cardiomyocyte size and enhancement of perivascular fibrosis were observed in
AT2KO-LPO. Interestingly, mRNA expression of collagen I and inflammatory
cytokines was markedly higher in the AT2KO-LPO heart at 6 weeks of age but not at
12 weeks of age. AT2R signaling may be involved in cardiovascular disorders of
adult offspring with FGR. Regulation of AT2R could contribute to preventing
future cardiovascular disease in FGR offspring.
PMID- 29335617
TI - Cardiovascular Function of Modern Pigs Does not Comply with Allometric Scaling
Laws.
AB - Growing concerns have been expressed regarding cardiovascular performance in
modern farm pigs, which has been proposed as a critical factor contributing to
the reduced adaptability of modern pigs to stress. Here we tested the hypothesis
that cardiac dimensions and pump function in modern heavy farm pigs are
disproportionally low for their body weight, and investigated potential
underlying mechanisms. The results from the present study indeed demonstrate
disproportionally low values for stroke volume and cardiac output in pigs with
bodyweights over 150 kg. Importantly, these low values were not the result of
impaired left ventricular (LV) systolic contractile function, but were due to a
disproportionally small LV end-diastolic volume. The latter was associated with
changes in determinants of LV passive stiffness, including (i) an increase in LV
myocardial collagen, (ii) a shift from the compliant N2BA titin isoform towards
the stiff N2B, and (iii) a marked elevation of aortic blood pressure. Taken
together, these results demonstrate reduced pumping capacity of the hearts of
heavy modern pigs, due to structural abnormalities in the LV myocardium.
PMID- 29335620
TI - Maternal, dominance and additive genetic effects in Nile tilapia; influence on
growth, fillet yield and body size traits.
AB - There are only few studies of dominance effects in non-inbred aquaculture
species, since commonly used mating designs often have low power to separate
dominance, maternal and common environmental effects. Here, a factorial design
with reciprocal cross, common rearing of eggs and subsequent lifecycle stages and
pedigree assignment using DNA microsatellites was used to separate these effects
and estimate dominance (d2) and maternal (m2) ratios in Nile tilapia for six
commercial traits. The study included observations on 2524 offspring from 155
full-sib families. Substantial contributions of dominance were observed (P <
0.05) for body depth (BD) and body weight at harvest (BWH) with estimates of d2 =
0.27 (s.e. 0.09) and 0.23 (s.e. 0.09), respectively in the current breeding
population. In addition the study found maternal variance (P < 0.05) for BD, BWH,
body thickness and fillet weight explaining ~10% of the observed phenotypic
variance. For fillet yield (FY) and body length (BL), no evidence was found for
either maternal or dominance variance. For traits exhibiting maternal variance,
including this effect in evaluations caused substantial re-ranking of selection
candidates, but the impact of including dominance effects was notably less.
Breeding schemes may benefit from utilising maternal variance in increasing
accuracy of evaluations, reducing bias, and developing new lines, but the
utilisation of the dominance variance may require further refinement of parameter
estimates.
PMID- 29335618
TI - Long-Term Maintenance of Human Pluripotent Stem Cells on cRGDfK-Presenting
Synthetic Surfaces.
AB - Synthetic human pluripotent stem cell (hPSC) culture surfaces with defined
physical and chemical properties will facilitate improved research and
therapeutic applications of hPSCs. In this study, synthetic surfaces for hPSC
culture in E8 medium were produced for screening by modifying two polymer brush
coatings [poly(acrylamide-co-acrylic acid) (PAAA) and poly(acrylamide-co
propargyl acrylamide) (PAPA)] to present single peptides. Adhesion of hPSC
colonies was more consistently observed on surfaces modified with cRGDfK compared
to surfaces modified with other peptide sequences tested. PAPA-coated polystyrene
flasks with coupled cRGDfK (cRGDfK-PAPA) were then used for long-term studies of
three hPSC lines (H9, hiPS-NHF1.3, Genea-02). Cell lines maintained for ten
passages on cRGDfK-PAPA were assessed for colony morphology, proliferation rate,
maintenance of OCT4 expression, cell viability at harvest, teratoma formation
potential, and global gene expression as assessed by the PluriTestTM assay.
cRGDfK-PAPA and control cultures maintained on GeltrexTM produced comparable
results in most assays. No karyotypic abnormalities were detected in cultures
maintained on cRGDfK-PAPA, while abnormalities were detected in cultures
maintained on GeltrexTM, StemAdhereTM or SynthemaxTM. This is the first report of
long term maintenance of hPSC cultures on the scalable, stable, and cost
effective cRGDfK-PAPA coating.
PMID- 29335619
TI - Cytokine MIF Enhances Blood-Brain Barrier Permeability: Impact for Therapy in
Ischemic Stroke.
AB - Ischemic stroke is a devastating disease with limited therapeutic options. It is
very urgent to find a new target for drug development. Here we found that the
blood level of MIF in ischemic stroke patients is upregulated. To figure out the
pathological role of MIF in ischemic stroke, both in vitro and in vivo studies
were conducted. For in vitro studies, primary cortical neuron cultures and adult
rat brain endothelial cells (ARBECs) were subjected to oxygen-glucose deprivation
(OGD)/reoxygenation. Middle cerebral artery occlusion (MCAo) rodent models were
used for in vivo studies. The results show that MIF exerts no direct neuronal
toxicity in primary culture but disrupts tight junction in ARBECs. Furthermore,
administration of MIF following MCAo shows the deleterious influence on stroke
induced injury by destroying the tight junction of blood-brain barrier and
increasing the infarct size. In contrast, administration of MIF antagonist ISO-1
has the profound neuroprotective effect. Our results demonstrate that MIF might
be a good drug target for the therapy of stroke.
PMID- 29335621
TI - Prognostic relevance of DNMT3A R882 mutations in AML patients undergoing non
myeloablative conditioning hematopoietic stem cell transplantation.
PMID- 29335622
TI - Topical vitamin D analog for chronic graft versus host disease of the skin.
PMID- 29335623
TI - Sinusoidal obstruction syndrome/veno-occlusive disease after high-dose
intravenous busulfan/melphalan conditioning therapy in high-risk Ewing Sarcoma.
AB - This mono-institutional observational study was conducted to determine incidence,
severity, risk factors, and outcome of sinusoidal obstruction syndrome/veno
occlusive disease (SOS/VOD) in high-risk Ewing sarcoma (ES) patients treated with
intravenous busulfan and melphalan (BU-MEL) followed by autologous stem cell
transplantation (ASCT). During the past 10 years, 75 consecutive ES patients
resulted evaluable for the analysis. After diagnosis of SOS/VOD, defibrotide
therapy was started as soon as the medication was available. The variables
analyzed as potential risk factors were: gender, patient's age at diagnosis,
primary tumor site, disease stage, and prior radiation therapy (RT) given,
focusing on RT liver exposure. The median age at diagnosis was 18.8 years. Five
patients developed moderate to severe SOS/VOD (cumulative incidence, 6.67%). None
of 32 pediatric patients (<=17 years) developed SOS/VOD (p = 0.0674). In
univariate analysis, prior RT liver exposure resulted statistically significant
(p = 0.0496). There was one death due to severe SOS/VOD. This study reports the
largest series of high-risk ES patients treated with intravenous BU-MEL before
ASCT. The incidence of SOS/VOD was lower when compared with other studies that
used oral busulfan. Any prior RT liver exposure should be avoided. Earlier
defibrotide treatment confirms to be effective.
PMID- 29335624
TI - Beneficial impact of low-dose rabbit anti-thymocyte globulin in unrelated
hematopoietic stem cell transplantation: focusing on difference between stem cell
sources.
PMID- 29335626
TI - Using liver elastography to diagnose sinusoidal obstruction syndrome in pediatric
patients undergoing hematopoetic stem cell transplant.
AB - Sinusoidal obstruction syndrome (SOS) is a potentially fatal complication of
hematopoietic stem cell transplantation (HSCT). Traditional ultrasound (US) has
poor sensitivity and specificity. US shear wave elastography (SWE) is a newer
technology that measures liver stiffness. This is a single-institution,
prospective cohort study evaluating SWE in patients younger than 21 years who
received HSCT from December 2015 through June 2017. SOS was defined using the
modified Seattle criteria. Subjects had US with SWE at three scheduled time
points. t-tests were used to assess for difference between the groups and ROC
curves were generated. Twenty-five patients were included. Five subjects
developed SOS. At day +5 HSCT, SOS patients had SWE velocities that increased by
0.25 +/- 0.21 m/s compared to 0.02 +/- 0.18 in patients without SOS (p = 0.020).
At day +14, SOS patients had SWE velocities that significantly increased by 0.91
m/s +/- 1.14 m/s compared to 0.03 m/s +/- 0.23 m/s in patients without SOS (p =
0.010). SWE SOS diagnosis occurred on average 9 and 11 days before clinical and
conventional US diagnosis, respectively. Patients who develop SOS have increased
liver stiffness compared to patients who do not develop SOS. SWE changes occur
before other imaging and clinical findings of SOS.
PMID- 29335625
TI - The European Society for Blood and Marrow Transplantation (EBMT) Consensus
Guidelines for the Detection and Treatment of Donor-specific Anti-HLA Antibodies
(DSA) in Haploidentical Hematopoietic Cell Transplantation.
AB - Haploidentical donors are now increasingly considered for transplantation in the
absence of HLA-matched donors or when an urgent transplant is needed. Donor
specific anti-HLA antibodies (DSA) have been recently recognized as an important
barrier against successful engraftment of donor cells, which can affect
transplant survival. DSA appear more prevalent in this type of transplant due to
higher likelihood of alloimmunization of multiparous females against offspring's
HLA antigens, and the degree of mismatch. Here we summarize the evidence for the
role of DSA in the development of primary graft failure in haploidentical
transplantation and provide consensus recommendations from the European Society
for Blood and Marrow Transplant Group on testing, monitoring, and treatment of
patients with DSA receiving haploidentical hematopoietic progenitor cell
transplantation.
PMID- 29335627
TI - A comparison of attitudes toward HSCT and survival estimations post HSCT across
two pediatric Hematology-Oncology and Intensive Care departments in Canada.
PMID- 29335628
TI - Endothelial cell damage in idiopathic pneumonia syndrome.
PMID- 29335629
TI - A prospective, randomized evaluation of the feasibility of exergaming on patients
undergoing hematopoietic stem cell transplantation.
AB - The positive effects of physical and sports therapy for strain dependent physical
practice and improved quality of life (QoL) are well known. Nevertheless, the
available capacities and problem-oriented therapies in the setting of
hematopoietic stem cell transplantation (HSCT) are limited. We conducted a
prospective, randomized study among 42 HSCT recipients in order to investigate
the influence of exergaming on Nintendo Wii(r) or classical physiotherapy (PT) on
physical fitness and psychological well-being. The trial included evaluation of
muscle strength, endurance, physical activity, distress, QoL, anxiety, and
depression. Within the first 2 weeks after HSCT endurance, muscle strength and
physical well-being decreased, while the value of distress increased
significantly in both groups. However, exergaming on Nintendo Wii(r) resulted in
a decrease of anxiety and depression and improved emotional well-being, while the
PT group showed a contrariwise pattern of these features. Analysis of the FACT
BMT revealed a decline of QoL domains 2 and 4 weeks after HSCT and an improvement
afterwards. The decrease of functional status after HSCT was accompanied by a
drop of QoL and an increase of distress in both groups. However, our prospective
study demonstrates that exergaming using the Nintendo Wii(r) is feasible and well
tolerated in HSCT recipients.
PMID- 29335630
TI - Haploidentical stem cell transplantation cures autoimmune hepatitis and
cerebrovascular disease in a patient with sickle cell disease.
PMID- 29335631
TI - Impact of HLA allele mismatch at HLA-A, -B, -C, -DRB1, and -DQB1 on outcomes in
haploidentical stem cell transplantation.
AB - The impact of human leukocyte antigen (HLA) allele mismatch on transplant
outcomes in haploidentical stem cell transplantation (haplo-SCT) has not been
established. We retrospectively studied 595 patients with hematologic malignancy
who received haplo-SCT. The impact of multiple HLA allele mismatches (HLA-A, -B,
C, -DRB1, and -DQB1) and each HLA allele mismatch on transplant outcomes was
analyzed. Greater number of HLA allele disparity does not appear worsen outcome.
As for each HLA locus, HLA-A mismatch correlated with decreased rate of platelet
engraftment (HR 0.740, P = .003); HLA-B mismatch independently correlated with
decreased relapse rate (HR 0.494, P = .032) and improved disease-free survival
and overall survival (HR 0.514, P = .003; HR 0.494, P = .002, respectively); HLA
C mismatch appeared to be protective for transplant-related mortality (TRM) (HR
0.567, P = .039); HLA-DRB1 mismatch was associated with increased cumulative
incidence of grade II-IV acute graft-vs.-host disease (GVHD) (HR 1.942, P =
.002). No associations of any HLA mismatch with delayed neutrophil engraftment or
increased cumulative incidence of chronic GVHD were observed. Our data indicated
that high degree of HLA allele mismatches did not adversely affect transplant
outcomes in haplo-SCT and each HLA allele mismatch had different effect.
PMID- 29335632
TI - Long-term outcome analysis of reduced-intensity allogeneic stem cell
transplantation in patients with mantle cell lymphoma: a retrospective study from
the EBMT Lymphoma Working Party.
AB - Reduced-intensity allogeneic stem cell transplantation (RIST) is usually reserved
for patients with mantle cell lymphoma who relapse after an autoSCT. However, the
long-term efficacy of RIST and its curative potential have not been clearly
demonstrated. We studied the long-term outcome of patients receiving a RIST for
MCL as reported to the EBMT. A total of 324 patients, median age 57 years (range
31-70), underwent a RIST between 2000 and 2008; 43% of the patients had received
>3 lines of prior therapy, including an autoSCT in 46%. Non-relapse mortality
(NRM) was 10% at 100 days and 24% at 1 year and was lower for patients receiving
anti-thymocyte globulin (ATG)/ALG (RR 0.59, p = 0.046). After a median follow-up
of 72 months (range 3-159), 118 patients relapsed at a median of 8 months post
RIST (range 1-117). The cumulative incidence of relapse was 25% and 40% at 1 and
5 years, respectively, and was associated with chemorefractory disease (HR 0.49,
p = 0.01) and the use of CAMPATH (HR 2.59, p = 0.0002). The 4-year progression
free survival rate and overall survival rate was 31 and 40%, respectively. RIST
results in long-term disease-free survival in about 30% of the patients,
including those patients relapsing after a prior autoSCT.
PMID- 29335633
TI - Long term survival among patients who are disease free at 1-year post allogeneic
hematopoietic cell transplantation: a single center analysis of 389 consecutive
patients.
AB - Allogeneic hematopoietic cell transplantation (HCT) is associated with
significant morbidity and mortality especially in the first year after HCT. In
this study, we examine the long-term outcomes of patients who survived at least
one year post HCT without evidence of relapse. We analyzed the records for 389
consecutive patients receiving an allogeneic transplant from 2005 to 2016 from a
MRD, MUD, or haploidentical donor, who were alive and disease free at one year
post-transplant. Patient characteristics and outcome parameters were extracted
from our institutional database where they had been prospectively entered. A
total of 389 patients met the selection criteria with donor graft including MRD
37%, MUD 39%, and Haploidenitcal relative 24%. The median follow-up of survivors
from time of HCT was 48.2 months. The median overall survival and disease-free
survival at 5 years after the first anniversary post HCT was 78 and 74%,
respectively. The most common causes of late mortality were disease relapse,
chronic GVHD and infections. The major risk factors for late mortality included
chronic GVHD requiring immunosuppression, being transplanted between 2005 and
2009 compared to later years and male sex. Patients with high risk disease risk
index (DRI) had worse OS compared to low risk DRI. The risk factors for late
relapse included male sex and high/very high disease risk index. The projected
long-term survival of 1-year survivors following allogeneic HCT is excellent.
However, some patients remain at high risk of late relapse and late mortality.
Early referral to transplant, adopting post-transplant consolidation strategies
for high risk patients, and implementing newer GVHD prevention methods are
potential interventions to help minimize the risk of late relapse and death.
PMID- 29335634
TI - The PII signaling protein from red algae represents an evolutionary link between
cyanobacterial and Chloroplastida PII proteins.
AB - PII superfamily consists of widespread signal transduction proteins found in all
domains of life. Whereas they are well-studied in Archaea, Bacteria and
Chloroplastida, no PII homolog has been analyzed in Rhodophyta (red algae), where
PII is encoded by a chloroplast localized glnB gene. Here, we characterized
relevant sensory properties of PII from the red alga Porphyra purpurea (PpPII) in
comparison to PII proteins from different phyla of oxygenic phototrophs
(cyanobacteria, Chlamydomonas and Physcomitrella) to assess evolutionary
conservation versus adaptive properties. Like its cyanobacterial counterparts,
PpPII binds ATP/ADP and 2-oxoglutarate in synergy with ATP. However, green algae
and land plant PII proteins lost the ability to bind ADP. In contrast to PII
proteins from green algae and land plants, PpPII enhances the activity of N
acetyl-L-glutamate kinase (NAGK) and relieves it from feedback inhibition by
arginine in a glutamine-independent manner. Like PII from Chloroplastida, PpPII
is not able to interact with the cyanobacterial transcriptional co-activator
PipX. These data emphasize the conserved role of NAGK as a major PII-interactor
throughout the evolution of oxygenic phototrophs, and confirms the specific role
of PipX for cyanobacteria. Our results highlight the PII signaling system in red
algae as an evolutionary intermediate between Cyanobacteria and Chlorophyta.
PMID- 29335636
TI - Saving seed microbiomes.
AB - Plant seeds are home to diverse microbial communities whose composition is
determined by plant genotype, environment, and management practices. Plant
domestication is now recognized as an important driver of plant-associated
microbial diversity. To what extent and how domestication affects seed
microbiomes is less well studied. Here we propose a 'back-to-the-future' approach
to harness seed microbiomes of wild relatives of crop cultivars to save and re
instate missing beneficial seed microbes for improved plant tolerance to biotic
and abiotic stress.
PMID- 29335635
TI - The emergence of metabolic heterogeneity and diverse growth responses in isogenic
bacterial cells.
AB - Microorganisms adapt to frequent environmental changes through population
diversification. Previous studies demonstrated phenotypic diversity in a clonal
population and its important effects on microbial ecology. However, the dynamic
changes of phenotypic composition have rarely been characterized. Also, cellular
variations and environmental factors responsible for phenotypic diversity remain
poorly understood. Here, we studied phenotypic diversity driven by metabolic
heterogeneity. We characterized metabolic activities and growth kinetics of
starved Escherichia coli cells subject to nutrient upshift at single-cell
resolution. We observed three subpopulations with distinct metabolic activities
and growth phenotypes. One subpopulation was metabolically active and immediately
grew upon nutrient upshift. One subpopulation was metabolically inactive and non
viable. The other subpopulation was metabolically partially active, and did not
grow upon nutrient upshift. The ratio of these subpopulations changed dynamically
during starvation. A long-term observation of cells with partial metabolic
activities indicated that their metabolism was later spontaneously restored,
leading to growth recovery. Further investigations showed that oxidative stress
can induce the emergence of a subpopulation with partial metabolic activities.
Our findings reveal the emergence of metabolic heterogeneity and associated
dynamic changes in phenotypic composition. In addition, the results shed new
light on microbial dormancy, which has important implications in microbial
ecology and biomedicine.
PMID- 29335637
TI - Expression profiling of host and virus during a coccolithophore bloom provides
insights into the role of viral infection in promoting carbon export.
AB - The cosmopolitan coccolithophore Emiliania huxleyi is a unicellular eukaryotic
alga that forms vast blooms in the oceans impacting large biogeochemical cycles.
These blooms are often terminated due to infection by the large dsDNA virus, E.
huxleyi virus (EhV). It was recently established that EhV-induced modulation of
E. huxleyi metabolism is a key factor for optimal viral infection cycle. Despite
the huge ecological importance of this host-virus interaction, the ability to
assess its spatial and temporal dynamics and its possible impact on nutrient
fluxes is limited by current approaches that focus on quantification of viral
abundance and biodiversity. Here, we applied a host and virus gene expression
analysis as a sensitive tool to quantify the dynamics of this interaction during
a natural E. huxleyi bloom in the North Atlantic. We used viral gene expression
profiling as an index for the level of active infection and showed that the
latter correlated with water column depth. Intriguingly, this suggests a possible
sinking mechanism for removing infected cells as aggregates from the E. huxleyi
population in the surface layer into deeper waters. Viral infection was also
highly correlated with induction of host metabolic genes involved in host life
cycle, sphingolipid, and antioxidant metabolism, providing evidence for
modulation of host metabolism under natural conditions. The ability to track and
quantify defined phases of infection by monitoring co-expression of viral and
host genes, coupled with advance omics approaches, will enable a deeper
understanding of the impact that viruses have on the environment.
PMID- 29335638
TI - Clearcutting alters decomposition processes and initiates complex restructuring
of fungal communities in soil and tree roots.
AB - Forest management practices often severely affect forest ecosystem functioning.
Tree removal by clearcutting is one such practice, producing severe impacts due
to the total reduction of primary productivity. Here, we assessed changes to
fungal community structure and decomposition activity in the soil, roots and
rhizosphere of a Picea abies stand for a 2-year period following clearcutting
compared to data from before tree harvest. We found that the termination of
photosynthate flow through tree roots into soil is associated with profound
changes in soil, both in decomposition processes and fungal community
composition. The rhizosphere, representing an active compartment of high enzyme
activity and high fungal biomass in the living stand, ceases to exist and starts
to resemble bulk soil. Decomposing roots appear to separate from bulk soil and
develop into hotspots of decomposition and important fungal biomass pools. We
found no support for the involvement of ectomycorrhizal fungi in the
decomposition of roots, but we found some evidence that root endophytic fungi may
have an important role in the early stages of this process. In soil, activity of
extracellular enzymes also decreased in the long term following the end of
rhizodeposition by tree roots.
PMID- 29335639
TI - Reply to the commentary "Uncultivated microbes-in need of their own
nomenclature?"
PMID- 29335640
TI - The stage of soil development modulates rhizosphere effect along a High Arctic
desert chronosequence.
AB - In mature soils, plant species and soil type determine the selection of root
microbiota. Which of these two factors drives rhizosphere selection in barren
substrates of developing desert soils has, however, not yet been established.
Chronosequences of glacier forelands provide ideal natural environments to
identify primary rhizosphere selection factors along the changing edaphic
conditions of a developing soil. Here, we analyze changes in bacterial diversity
in bulk soils and rhizospheres of a pioneer plant across a High Arctic glacier
chronosequence. We show that the developmental stage of soil strongly modulates
rhizosphere community assembly, even though plant-induced selection buffers the
effect of changing edaphic factors. Bulk and rhizosphere soils host distinct
bacterial communities that differentially vary along the chronosequence. Cation
exchange capacity, exchangeable potassium, and metabolite concentration in the
soil account for the rhizosphere bacterial diversity. Although the soil fraction
(bulk soil and rhizosphere) explains up to 17.2% of the variation in bacterial
microbiota, the soil developmental stage explains up to 47.7% of this variation.
In addition, the operational taxonomic unit (OTU) co-occurrence network of the
rhizosphere, whose complexity increases along the chronosequence, is loosely
structured in barren compared with mature soils, corroborating our hypothesis
that soil development tunes the rhizosphere effect.
PMID- 29335641
TI - Benefit from decline: the primary transcriptome of Alteromonas macleodii str.
Te101 during Trichodesmium demise.
AB - Interactions between co-existing microorganisms deeply affect the physiology of
the involved organisms and, ultimately, the function of the ecosystem as a whole.
Copiotrophic Alteromonas are marine gammaproteobacteria that thrive during the
late stages of phytoplankton blooms in the marine environment and in laboratory
co-cultures with cyanobacteria such as Trichodesmium. The response of this
heterotroph to the sometimes rapid and transient changes in nutrient supply when
the phototroph crashes is not well understood. Here, we isolated and sequenced
the strain Alteromonas macleodii str. Te101 from a laboratory culture of
Trichodesmium erythraeum IMS101, yielding a chromosome of 4.63 Mb and a single
plasmid of 237 kb. Increasing salinities to >=43 ppt inhibited the growth of
Trichodesmium but stimulated growth of the associated Alteromonas. We
characterized the transcriptomic responses of both microorganisms and identified
the complement of active transcriptional start sites in Alteromonas at single
nucleotide resolution. In replicate cultures, a similar set of genes became
activated in Alteromonas when growth rates of Trichodesmium declined and
mortality was high. The parallel activation of fliA, rpoS and of flagellar
assembly and growth-related genes indicated that Alteromonas might have increased
cell motility, growth, and multiple biosynthetic activities. Genes with the
highest expression in the data set were three small RNAs (Aln1a-c) that were
identified as analogs of the small RNAs CsrB-C in E. coli or RsmX-Z in pathogenic
bacteria. Together with the carbon storage protein A (CsrA) homolog Te101_05290,
these RNAs likely control the expression of numerous genes in responding to
changes in the environment.
PMID- 29335642
TI - Controlled dynamic screening of excitonic complexes in 2D semiconductors.
AB - We report a combined theoretical/experimental study of dynamic screening of
excitons in media with frequency-dependent dielectric functions. We develop an
analytical model showing that interparticle interactions in an exciton are
screened in the range of frequencies from zero to the characteristic binding
energy depending on the symmetries and transition energies of that exciton. The
problem of the dynamic screening is then reduced to simply solving the
Schrodinger equation with an effectively frequency-independent potential.
Quantitative predictions of the model are experimentally verified using a test
system: neutral, charged and defect-bound excitons in two-dimensional monolayer
WS2, screened by metallic, liquid, and semiconducting environments. The screening
induced shifts of the excitonic peaks in photoluminescence spectra are in good
agreement with our model.
PMID- 29335643
TI - Decoding Musical Training from Dynamic Processing of Musical Features in the
Brain.
AB - Pattern recognition on neural activations from naturalistic music listening has
been successful at predicting neural responses of listeners from musical
features, and vice versa. Inter-subject differences in the decoding accuracies
have arisen partly from musical training that has widely recognized structural
and functional effects on the brain. We propose and evaluate a decoding approach
aimed at predicting the musicianship class of an individual listener from dynamic
neural processing of musical features. Whole brain functional magnetic resonance
imaging (fMRI) data was acquired from musicians and nonmusicians during listening
of three musical pieces from different genres. Six musical features, representing
low-level (timbre) and high-level (rhythm and tonality) aspects of music
perception, were computed from the acoustic signals, and classification into
musicians and nonmusicians was performed on the musical feature and parcellated
fMRI time series. Cross-validated classification accuracy reached 77% with nine
regions, comprising frontal and temporal cortical regions, caudate nucleus, and
cingulate gyrus. The processing of high-level musical features at right superior
temporal gyrus was most influenced by listeners' musical training. The study
demonstrates the feasibility to decode musicianship from how individual brains
listen to music, attaining accuracy comparable to current results from automated
clinical diagnosis of neurological and psychological disorders.
PMID- 29335645
TI - The new genetics of intelligence.
AB - Intelligence - the ability to learn, reason and solve problems - is at the
forefront of behavioural genetic research. Intelligence is highly heritable and
predicts important educational, occupational and health outcomes better than any
other trait. Recent genome-wide association studies have successfully identified
inherited genome sequence differences that account for 20% of the 50%
heritability of intelligence. These findings open new avenues for research into
the causes and consequences of intelligence using genome-wide polygenic scores
that aggregate the effects of thousands of genetic variants.
PMID- 29335646
TI - Dipeptidyl peptidase-4 inhibitors, pancreatic cancer and acute pancreatitis: A
meta-analysis with trial sequential analysis.
AB - The use of dipeptidyl peptidase-4 (DPP-4) inhibitors may be associated with
pancreatic cancer and acute pancreatitis. Recent meta-analyses have reported
conflicting findings. Therefore, we performed a meta-analysis to assess the risk
of both pancreatic cancer and acute pancreatitis associated with the use of DPP-4
inhibitors. We also used trial sequential analysis to evaluate whether the number
of patients included was enough to reach conclusions. We included randomised
controlled trials lasting 24 weeks or more that compared DPP-4 inhibitors with
placebo or other antihyperglycaemic agents. A total of 59,404 patients were
included. There was no relationship between the use of DPP-4 inhibitors and
pancreatic cancer (Peto odds ratio 0.65; 95% CI 0.35-1.21), and the optimal
sample size was reached to determine a number needed to harm (NNH) of 1000
patients. DPP-4 inhibitors were associated with increased risk for acute
pancreatitis (Peto odds ratio 1.72; 95% CI 1.18-2.53), with an NNH of 1066
patients, but the optimal sample size for this outcome was not reached. In
conclusion, there is no association between DPP-4 inhibitors and pancreatic
cancer, and a small risk for acute pancreatitis was observed with DPP-4 inhibitor
use, although the latter finding is not definitive.
PMID- 29335644
TI - Runs of homozygosity: windows into population history and trait architecture.
AB - Long runs of homozygosity (ROH) arise when identical haplotypes are inherited
from each parent and thus a long tract of genotypes is homozygous. Cousin
marriage or inbreeding gives rise to such autozygosity; however, genome-wide data
reveal that ROH are universally common in human genomes even among outbred
individuals. The number and length of ROH reflect individual demographic history,
while the homozygosity burden can be used to investigate the genetic architecture
of complex disease. We discuss how to identify ROH in genome-wide microarray and
sequence data, their distribution in human populations and their application to
the understanding of inbreeding depression and disease risk.
PMID- 29335647
TI - Aged polymorphonuclear leukocytes cause fibrotic interstitial lung disease in the
absence of regulation by B cells.
AB - Pulmonary immunity requires tight regulation, as interstitial inflammation can
compromise gas exchange and lead to respiratory failure. Here we found a greater
number of aged CD11bhiL-selectinloCXCR4+ polymorphonuclear leukocytes (PMNs) in
lung vasculature than in the peripheral circulation. Using pulmonary intravital
microscopy, we observed lung PMNs physically interacting with B cells via beta2
integrins; this initiated neutrophil apoptosis, which led to macrophage-mediated
clearance. Genetic deletion of B cells led to the accumulation of aged PMNs in
the lungs without systemic inflammation, which caused pathological fibrotic
interstitial lung disease that was attenuated by the adoptive transfer of B cells
or depletion of PMNs. Thus, the lungs are an intermediary niche in the PMN
lifecycle wherein aged PMNs are regulated by B cells, which restrains their
potential to cause pulmonary pathology.
PMID- 29335650
TI - CNS cancer: TTFields improve survival.
PMID- 29335648
TI - Rapid chromatin repression by Aire provides precise control of immune tolerance.
AB - Aire mediates the expression of tissue-specific antigens in thymic epithelial
cells to promote tolerance against self-reactive T lymphocytes. However, the
mechanism that allows expression of tissue-specific genes at levels that prevent
harm is unknown. Here we show that Brg1 generates accessibility at tissue
specific loci to impose central tolerance. We found that Aire has an intrinsic
repressive function that restricts chromatin accessibility and opposes Brg1
across the genome. Aire exerted this repressive influence within minutes after
recruitment to chromatin and restrained the amplitude of active transcription.
Disease-causing mutations that impair Aire-induced activation also impair the
protein's repressive function, which indicates dual roles for Aire. Together,
Brg1 and Aire fine-tune the expression of tissue-specific genes at levels that
prevent toxicity yet promote immune tolerance.
PMID- 29335649
TI - Hyaluronic acid-based nano-sized drug carrier-containing Gellan gum microspheres
as potential multifunctional embolic agent.
AB - The purpose of this study was to develop a gellan gum-based multifunctional
embolic agent. Calibrated spherical gellan gum and nanoparticle-containing gellan
gum microspheres were prepared via water-in oil emulsification method. Self
assembled nanoparticles composed of short-chain hyaluronic acid and
polyethylenimine as the doxorubicin carrier were prepared. The short-chain
hyaluronic acid/polyethylenimine/ doxorubicin (sHH/PH/Dox) with the mean size was
140 +/- 8 nm. To examine sHH/PH/Dox nanoparticle uptake into cells, the results
confirmed that sHH/PH nanoparticles as drug carrier can facilitate the transport
of doxorubicin into HepG2 liver cancer cells. Subsequently, sHH/PH/Dox merged
into the gellan gum (GG) microspheres forming GG/sHH/PH/Dox microsphere. After a
drug release experiment lasting 45 days, the amount of released doxorubicin from
285, 388, and 481 MUm GG/sHH/PH/Dox microspheres were approximately 4.8, 1.8 and
1.1-fold above the IC50 value of the HepG2 cell. GG/sHH/PH/Dox microspheres were
performed in rabbit ear embolization model and ischemic necrosis on ear was
visible due to the vascular after 8 days. Regarding the application of this
device in the future, we aim to provide better embolization agents for
transcatheter arterial chemoembolization (TACE).
PMID- 29335651
TI - Haematological cancer: Daratumumab proves effective in patients with newly
diagnosed multiple myeloma.
PMID- 29335652
TI - Kidney cancer: First-in-class HIF2alpha antagonist safe and effective.
PMID- 29335653
TI - Will a global fund for cancer be the answer?
PMID- 29335654
TI - Microwave SQUID Multiplexer Demonstration for Cosmic Microwave Background
Imagers.
AB - Key performance characteristics are demonstrated for the microwave SQUID
multiplexer (umux) coupled to transition edge sensor (TES) bolometers that have
been optimized for cosmic microwave background (CMB) observations. In a 64
channel demonstration, we show that the umux produces a white, input referred
current noise level of [Formula: see text] at -77 dB microwave probe tone power,
which is well below expected fundamental detector and photon noise sources for a
ground-based CMB-optimized bolometer. Operated with negligible photon loading, we
measure [Formula: see text] in the TES-coupled channels biased at 65% of the
sensor normal resistance. This noise level is consistent with that predicted from
bolometer thermal fluctuation (i.e. phonon) noise. Furthermore, the power
spectral density is white over a range of frequencies down to ~ 100 mHz, which
enables CMB mapping on large angular scales that constrain the physics of
inflation. Additionally, we report cross-talk measurements that indicate a level
below 0.3%, which is less than the level of cross-talk from multiplexed readout
systems in deployed CMB imagers. These measurements demonstrate the umux as a
viable readout technique for future CMB imaging instruments.
PMID- 29335655
TI - A Bifactor Approach to Model Multifaceted Constructs in Statistical Mediation
Analysis.
AB - Statistical mediation analysis allows researchers to identify the most important
mediating constructs in the causal process studied. Identifying specific
mediators is especially relevant when the hypothesized mediating construct
consists of multiple related facets. The general definition of the construct and
its facets might relate differently to an outcome. However, current methods do
not allow researchers to study the relationships between general and specific
aspects of a construct to an outcome simultaneously. This study proposes a
bifactor measurement model for the mediating construct as a way to parse variance
and represent the general aspect and specific facets of a construct
simultaneously. Monte Carlo simulation results are presented to help determine
the properties of mediated effect estimation when the mediator has a bifactor
structure and a specific facet of a construct is the true mediator. This study
also investigates the conditions when researchers can detect the mediated effect
when the multidimensionality of the mediator is ignored and treated as
unidimensional. Simulation results indicated that the mediation model with a
bifactor mediator measurement model had unbiased and adequate power to detect the
mediated effect with a sample size greater than 500 and medium a- and b-paths.
Also, results indicate that parameter bias and detection of the mediated effect
in both the data-generating model and the misspecified model varies as a function
of the amount of facet variance represented in the mediation model. This study
contributes to the largely unexplored area of measurement issues in statistical
mediation analysis.
PMID- 29335657
TI - Changing Gender Norms and Marriage Dynamics in the United States.
AB - Using a regional measure of gender norms from the General Social Surveys together
with marital histories from the Panel Study of Income Dynamics, this study
explored how gender norms were associated with women's marriage dynamics between
1968 and 2012. Results suggested that a higher prevalence of egalitarian gender
norms predicted a decline in marriage formation. This decline was, however, only
true for women without a college degree. For college-educated women, the
association between gender norms and marriage formation became positive when
gender egalitarianism prevailed. The findings also revealed an inverted U-shaped
relationship between gender norms and divorce: an initial increase in divorce was
observed when gender norms were predominantly traditional. The association,
however, reversed as gender norms became egalitarian. No differences by education
were found for divorce. The findings partially support the gender revolution
framework but also highlight greater barriers to marriage for low-educated women
as societies embrace gender equality.
PMID- 29335656
TI - Hydrogen-Atom Transfer Oxidation with H2O2 Catalyzed by [FeII(1,2-bis(2,2'
bipyridyl-6-yl)ethane(H2O)2]2+: Likely Involvement of a (MU-Hydroxo)(MU-1,2
peroxo)diiron(III) Intermediate.
AB - The iron(II) triflate complex (1) of 1,2-bis(2,2'-bipyridyl-6-yl)ethane, with two
bipyridine moieties connected by an ethane bridge, was prepared. Addition of
aqueous 30% H2O2 to an acetonitrile solution of 1 yielded 2, a green compound
with lambdamax=710 nm. Moessbauer measurements on 2 showed a doublet with an
isomer shift (delta) of 0.35 mm/s and a quadrupole splitting (DeltaEQ) of 0.86
mm/s, indicative of an antiferromagnetically coupled diferric complex. Resonance
Raman spectra showed peaks at 883, 556 and 451 cm-1 that downshifted to 832, 540
and 441 cm-1 when 1 was treated with H218O2. All the spectroscopic data support
the initial formation of a (MU-hydroxo)(MU-1,2-peroxo)diiron(III) complex that
oxidizes carbon-hydrogen bonds. At 0 degrees C 2 reacted with cyclohexene to
yield allylic oxidation products but not epoxide. Weak benzylic C-H bonds of
alkylarenes were also oxidized. A plot of the logarithms of the second order rate
constants versus the bond dissociation energies of the cleaved C-H bond showed an
excellent linear correlation. Along with the observation that oxidation of the
probe substrate 2,2-dimethyl-1-phenylpropan-1-ol yielded the corresponding ketone
but no benzaldehyde, and the kinetic isotope effect, kH/kD , of 2.8 found for the
oxidation of xanthene, the results support the hypothesis for a metal-based H
atom abstraction mechanism. Complex 2 is a rare example of a (MU-hydroxo)(MU-1,2
peroxo)diiron(III) complex that can elicit the oxidation of carbon-hydrogen
bonds.
PMID- 29335659
TI - Recommendation System for Adaptive Learning.
AB - An adaptive learning system aims at providing instruction tailored to the current
status of a learner, differing from the traditional classroom experience. The
latest advances in technology make adaptive learning possible, which has the
potential to provide students with high-quality learning benefit at a low cost. A
key component of an adaptive learning system is a recommendation system, which
recommends the next material (video lectures, practices, and so on, on different
skills) to the learner, based on the psychometric assessment results and possibly
other individual characteristics. An important question then follows: How should
recommendations be made? To answer this question, a mathematical framework is
proposed that characterizes the recommendation process as a Markov decision
problem, for which decisions are made based on the current knowledge of the
learner and that of the learning materials. In particular, two plain vanilla
systems are introduced, for which the optimal recommendation at each stage can be
obtained analytically.
PMID- 29335658
TI - Highly Stereoselective Asymmetric Aldol Routes to tert-Butyl-2-(3,5
difluorophenyl)-1-oxiran-2-yl)ethyl)carbamates: Building Blocks for Novel
Protease Inhibitors.
AB - Enantioselective syntheses of tert-butyl ((S)-2-(3,5-difluorophenyl)-1-((S)
oxiran-2-yl)ethyl)carbamate and ((S)-2-(3,5-difluorophenyl)-1-((R)-oxiran-2
yl)ethyl)carbamate are described. We utilized asymmetric syn- and anti-aldol
reactions to set both stereogenic centers. We investigated ester-derived Ti
enolate aldol reactions as well as Evans' diastereoselective syn-aldol reaction
for these syntheses. We have converted optically active ((S)-2-(3,5
difluorophenyl)-1-((S)-oxiran-2-yl)ethyl)carbamate to a potent beta-secretase
inhibitor.
PMID- 29335660
TI - Can Linear Superiorization Be Useful for Linear Optimization Problems?
AB - Linear superiorization considers linear programming problems but instead of
attempting to solve them with linear optimization methods it employs perturbation
resilient feasibility-seeking algorithms and steers them toward reduced (not
necessarily minimal) target function values. The two questions that we set out to
explore experimentally are (i) Does linear superiorization provide a feasible
point whose linear target function value is lower than that obtained by running
the same feasibility-seeking algorithm without superiorization under identical
conditions? and (ii) How does linear superiorization fare in comparison with the
Simplex method for solving linear programming problems? Based on our
computational experiments presented here, the answers to these two questions are:
"yes" and "very well", respectively.
PMID- 29335661
TI - Weather Correlations to Calculate Infiltration Rates for U. S. Commercial
Building Energy Models.
AB - As building envelope performance improves, a greater percentage of building
energy loss will occur through envelope leakage. Although the energy impacts of
infiltration on building energy use can be significant, current energy simulation
software have limited ability to accurately account for envelope infiltration and
the impacts of improved airtightness. This paper extends previous work by the
National Institute of Standards and Technology that developed a set of EnergyPlus
inputs for modeling infiltration in several commercial reference buildings using
Chicago weather. The current work includes cities in seven additional climate
zones and uses the updated versions of the prototype commercial building types
developed by the Pacific Northwest National Laboratory for the U. S. Department
of Energy. Comparisons were made between the predicted infiltration rates using
three representations of the commercial building types: PNNL EnergyPlus models,
CONTAM models, and EnergyPlus models using the infiltration inputs developed in
this paper. The newly developed infiltration inputs in EnergyPlus yielded average
annual increases of 3 % and 8 % in the HVAC electrical and gas use, respectively,
over the original infiltration inputs in the PNNL EnergyPlus models. When
analyzing the benefits of building envelope airtightening, greater HVAC energy
savings were predicted using the newly developed infiltration inputs in
EnergyPlus compared with using the original infiltration inputs. These results
indicate that the effects of infiltration on HVAC energy use can be significant
and that infiltration can and should be better accounted for in whole-building
energy models.
PMID- 29335662
TI - Is Nebulin the Product of Duchenne Muscular Dystrophy Gene?
PMID- 29335663
TI - Improving Mental Health Treatment Utilization in Military Veterans: Examining the
Effects of Perceived Need for Care and Social Support.
AB - Objective: Many veterans with mental health problems do not adequately utilize
needed care. Research has focused on identifying barriers to mental health care
in veterans. Method: The current study adds to existing literature by examining
whether perceived need for treatment and social support affect treatment
utilization in a national longitudinal survey of Iraq and Afghanistan veterans (n
= 1090). Results: The Health Beliefs Model (HBM) postulates that a key reason why
patients fail to obtain needed care is their belief "it's up to me to handle my
own problems." This view was endorsed by 42% in the current national sample of
veterans and was found in multivariate analysis to predict less treatment seeking
in the next year. Mediation analysis revealed that veterans with higher ratings
of social support were less likely to believe they needed to solve mental health
problems on their own, indirectly equating to higher odds of treatment use.
Simultaneously, findings indicated that posttraumatic stress disorder (PTSD) had
a direct effect on more mental health visits but was also associated with higher
endorsement that one needed to handle one's own problems and thus had an indirect
effect of reducing mental health visits. Conclusion: Both social support and PTSD
affected veterans' perceptions of needing to solve one's own problems,
significantly predicted follow-up with mental health care. As a result, the
findings indicate that clinicians' should explore veterans' belief systems about
perceived treatment need as well as investigate the role of social support to
improve mental health treatment utilization.
PMID- 29335664
TI - Applying a biodeposition layer to increase the bond of a repair mortar on a
mortar substrate.
AB - One of the major concerns in infrastructure repair is a sufficient bond between
the substrate and the repair material, especially for the long-term performance
and durability of the repaired structure. In this study, the bond of the repair
material on the mortar substrate is promoted via the biodeposition of a calcium
carbonate layer by a ureolytic bacterium. X-ray diffraction and scanning electron
microscopy were used to examine the interfaces between the repair material and
the substrate, as well as the polymorph of the deposited calcium carbonate. The
approximately 50 MUm thick biodeposition film on the mortar surface mostly
consisted of calcite and vaterite. Both the repair material and the substrate
tended to show a good adherence to that layer. The bond, as assessed by slant
shear specimen testing, was improved by the presence of the biodeposition layer.
A further increase was found when engineering the substrate surface using a
structured pattern layer of biodeposition.
PMID- 29335665
TI - Self-Control as Value-Based Choice.
AB - Self-control is often conceived as a battle between "hot" impulsive processes and
"cold" deliberative ones. Heeding the angel on one shoulder leads to success;
following the demon on the other leads to failure. Self-control feels like a
duality. What if that sensation is misleading, and, despite how they feel, self
control decisions are just like any other choice? We argue that self-control is a
form of value-based choice wherein options are assigned a subjective value and a
decision is made through a dynamic integration process. We articulate how a value
based choice model of self-control can capture its phenomenology and account for
relevant behavioral and neuroscientific data. This conceptualization of self
control links divergent scientific approaches, allows for more robust and precise
hypothesis testing, and suggests novel pathways to improve self-control.
PMID- 29335666
TI - A Modified Dynamic Surface Controller for Delayed Neuromuscular Electrical
Stimulation.
AB - A widely accepted model of muscle force generation during neuromuscular
electrical stimulation (NMES) is a second-order nonlinear musculoskeletal
dynamics cascaded to a delayed first-order muscle activation dynamics. However,
most nonlinear NMES control methods have either neglected the muscle activation
dynamics or used an ad hoc strategies to tackle the muscle activation dynamics,
which may not guarantee control stability. We hypothesized that a nonlinear
control design that includes muscle activation dynamics can improve the control
performance. In this paper, a dynamic surface control (DSC) approach was used to
design a PID-based NMES controller that compensates for EMD in the activation
dynamics. Because the muscle activation is unmeasurable, a model based estimator
was used to estimate the muscle activation in realtime. The Lyapunov stability
analysis confirmed that the newly developed controller achieves semi-global
uniformly ultimately bounded (SGUUB) tracking for the musculoskeletal system.
Experiments were performed on two able-bodied subjects and one spinal cord injury
subject using a modified leg extension machine. These experiments illustrate the
performance of the new controller and compare it to a previous PID-DC controller
that did not consider muscle activation dynamics in the control design. These
experiments support our hypothesis that a control design that includes muscle
activation improves the NMES control performance.
PMID- 29335667
TI - Zero-inflated multiscale models for aggregated small area health data.
AB - It is our primary focus to study the spatial distribution of disease incidence at
different geographical levels. Often, spatial data are available in the form of
aggregation at multiple scale levels such as census tract, county, state, and so
on. When data are aggregated from a fine (e.g. county) to a coarse (e.g. state)
geographical level, there will be loss of information. The problem is more
challenging when excessive zeros are available at the fine level. After data
aggregation, the excessive zeros at the fine level will be reduced at the coarse
level. If we ignore the zero inflation and the aggregation effect, we could get
inconsistent risk estimates at the fine and coarse levels. Hence, in this paper,
we address those problems using zero inflated multiscale models that jointly
describe the risk variations at different geographical levels. For the excessive
zeros at the fine level, we use a zero inflated convolution model, whereas we
consider a regular convolution model for the smoothed data at the coarse level.
These methods provide a consistent risk estimate at the fine and coarse levels
when high percentages of structural zeros are present in the data.
PMID- 29335668
TI - Bayesian Empirical Likelihood Methods for Quantile Comparisons.
AB - Bayes factors, practical tools of applied statistics, have been dealt with
extensively in the literature in the context of hypothesis testing. The Bayes
factor based on parametric likelihoods can be considered both as a pure Bayesian
approach as well as a standard technique to compute p-values for hypothesis
testing. We employ empirical likelihood methodology to modify Bayes factor type
procedures for the nonparametric setting. The paper establishes asymptotic
approximations to the proposed procedures. These approximations are shown to be
similar to those of the classical parametric Bayes factor approach. The proposed
approach is applied towards developing testing methods involving quantiles, which
are commonly used to characterize distributions. We present and evaluate one and
two sample distribution free Bayes factor type methods for testing quantiles
based on indicators and smooth kernel functions. An extensive Monte Carlo study
and real data examples show that the developed procedures have excellent
operating characteristics for one-sample and two-sample data analysis.
PMID- 29335669
TI - Portable FAIMS: Applications and Future Perspectives.
AB - Miniaturized mass spectrometry (MMS) is optimal for a wide variety of
applications that benefit from field-portable instrumentation. Like MMS, field
asymmetric ion mobility spectrometry (FAIMS) has proven capable of providing in
situ analysis, allowing researchers to bring the lab to the sample. FAIMS
compliments MMS very well, but has the added benefit of operating at atmospheric
pressure, unlike MS. This distinct advantage makes FAIMS uniquely suited for
portability. Since its inception, FAIMS has been envisioned as a field-portable
device, as it affords less expense and greater simplicity than many similar
methods. Ideally, these are simple, robust devices that may be operated by non
professional personnel, yet still provide adequate data when in the field. While
reducing the size and complexity tends to bring with it a loss of performance and
accuracy, this is made up for by the incredibly high throughput and overall
convenience of the instrument. Moreover, the FAIMS device used in the field can
be brought back to the lab, and coupled to a conventional mass spectrometer to
provide any necessary method development and compound validation. This work
discusses the various considerations, uses, and applications for portable FAIMS
instrumentation, and how the future of each applicable field may benefit from the
development and acceptance of such a device.
PMID- 29335670
TI - Big Data and Neuroimaging.
AB - Big Data are of increasing importance in a variety of areas, especially in the
biosciences. There is an emerging critical need for Big Data tools and methods,
because of the potential impact of advancements in these areas. Importantly,
statisticians and statistical thinking have a major role to play in creating
meaningful progress in this arena. We would like to emphasize this point in this
special issue, as it highlights both the dramatic need for statistical input for
Big Data analysis and for a greater number of statisticians working on Big Data
problems. We use the field of statistical neuroimaging to demonstrate these
points. As such, this paper covers several applications and novel methodological
developments of Big Data tools applied to neuroimaging data.
PMID- 29335671
TI - Feasibility, Acceptability, and Preliminary Effectiveness of a 4-week Mindfulness
Based Cognitive Therapy Protocol for Hospital Employees.
AB - Hospital employees may experience occupational stress and burnout, which
negatively impact quality of life and job performance. Evidence-based
interventions implemented within the hospital setting are needed to promote
employees' well-being. We offered a 4-week Mindfulness-Based Cognitive Therapy
group program for hospital employees, and used a mixed-methods practice-based
research approach to explore feasibility, acceptability, and effects on stress
and burnout. Participants were 65 hospital employees (Mage = 44.06; 85% white)
who participated between September 2015 and January 2016. Participants completed
validated measures of stress and burnout before and after the program, and
answered open-ended satisfaction questions after the program. Groups consistently
enrolled at least 10 participants, but attendance rates declined across sessions
(76% at session 2 vs. 54% at session 4) due primarily to work-related scheduling
conflicts. The program content was acceptable as evidenced by high perceived
value (M = 9.18 out of 10), homework compliance (51% practicing at least 3
times/week), and qualitative requests for program expansion. There were large,
statistically significant decreases in stress (DeltaM = 2.1, p < .001, d = .85)
and medium decreases in burnout (DeltaM = .46, p = .01, d = .57), which were
supported by qualitative themes of improved self-regulation and mindfulness
skills, stress reduction, emotional well-being, and improved work productivity
and patient care skills. Findings suggest that 4-week MBCT is acceptable and
useful for hospital employees, though research is needed to identify alternate
delivery methods or strategies to enhance session attendance.
PMID- 29335672
TI - Seeing Roses in the Thorn Bush: Sexual Assault Survivors' Perceptions of Social
Reactions.
AB - Objective: After sexual assault, survivors often reach to others for support and
receive a range of reactions. Although these reactions have been characterized by
researchers as positive (e.g., emotional support) or negative (e.g., victim
blaming), survivors vary in their perceptions in ways that do not always match
this framework. The goal of this research was to examine the degree to which
designations of reactions as "positive" or "negative" fits across types of
reactions and explain instances of mismatch between these designations and
survivors' perceptions. Method: We conducted a qualitative analysis of interviews
with 26 survivors of sexual assault to identify themes in their perceptions of
social reactions. Results: Although social reactions were generally perceived in
a manner that matched researcher categorizations, there was significant
variation. Perceptions could be characterized in terms of whether the reaction
felt comfortable/soothing, consistent with survivors' needs/hopes/expectations,
and helpful in the long term. The closeness of survivors' relationships with
responders, the degree to which they were impacted by the assault, and the
presence of other social reactions explained variation from researcher
designations of reaction types. Conclusion: This study clarifies the
considerations that survivors make when evaluating social reactions and what
accounts for discrepant perceptions of these reactions; in particular, they
highlight that there is no "one size fits all" reaction to survivors of sexual
assault and the context in which reactions occur may affect how they are seen.
PMID- 29335673
TI - Desistance and Severity of Alcohol Use Disorder: A Lifespan-Developmental
Investigation.
AB - Key to an understanding of alcohol use disorder (AUD) are the drinking-related
reductions that begin in young adulthood and continue throughout the adult
lifespan. Research is needed to precisely characterize the form of these
reductions, including possible developmental differences across the lifespan.
Using U.S.-representative data, we estimated multiple-group Markov models
characterizing longitudinal transitions among five drinking statuses and
differences in transition patterns across six adult age periods. While past
research indicates relative developmental stability in overall AUD-desistance
rates, we found far higher rates of Severe-AUD desistance in young adulthood
relative to later ages. Especially considering the dramatic change reflected by
Severe-AUD desistance (from 6+ symptoms to 0-1 symptoms), this result indicates a
substantial developmental shift, with Severe-AUD-desistance rates peaking at 43
50% across ages 25-34 and then dropping to 22-24% across ages 35-55. We discuss
implications regarding practical significance of young-adult "maturing out" and
predictions regarding lifespan variability in desistance mechanisms.
PMID- 29335675
TI - Exit, cohesion, and consensus: social psychological moderators of consensus among
adolescent peer groups.
AB - Virtually all social diffusion work relies on a common formal basis, which
predicts that consensus will develop among a connected population as the result
of diffusion. In spite of the popularity of social diffusion models that predict
consensus, few empirical studies examine consensus, or a clustering of attitudes,
directly. Those that do either focus on the coordinating role of strict
hierarchies, or on the results of online experiments, and do not consider how
consensus occurs among groups in situ. This study uses longitudinal data on
adolescent social networks to show how meso-level social structures, such as
informal peer groups, moderate the process of consensus formation. Using a novel
method for controlling for selection into a group, I find that centralized peer
groups, meaning groups with clear leaders, have very low levels of consensus,
while cohesive peer groups, meaning groups where more ties hold the members of
the group together, have very high levels of consensus. This finding is robust to
two different measures of cohesion and consensus. This suggests that consensus
occurs either through central leaders' enforcement or through diffusion of
attitudes, but that central leaders have limited ability to enforce when people
can leave the group easily.
PMID- 29335676
TI - Behavioral Assays to Study Oxygen and Carbon Dioxide Sensing in Caenorhabditis
elegans.
AB - Animals use behavioral strategies to seek optimal environments. Population
behavioral assays provide a robust means to determine the effect of genetic
perturbations on the ability of animals to sense and respond to changes in the
environment. Here, we describe a C. elegans population behavioral assay used to
measure locomotory responses to changes in environmental oxygen (O2) and carbon
dioxide (CO2) concentrations. These behavioral assays are high-throughput and
enable examination of genetic, neuronal and circuit function.
PMID- 29335677
TI - Two-dimensional imaging and modification of nanophotonic resonator modes using a
focused ion beam.
AB - High-resolution imaging of optical resonator modes is a key step in the
development and characterization of nanophotonic devices. Many sub-wavelength
mode-imaging techniques have been developed using optical and electron beam
excitation-each with its own limitations in spectral and spatial resolution.
Here, we report a 2D imaging technique using a pulsed, low-energy focused ion
beam of Li+ to probe the near-surface fields inside photonic resonators. The ion
beam locally modifies the resonator structure, causing temporally varying
spectroscopic shifts of the resonator. We demonstrate this imaging technique on
several optical modes of silicon microdisk resonators by rastering the ion beam
across the disk surface and extracting the maximum mode shift at the location of
each ion pulse. A small shift caused by ion beam heating is also observed and is
independently extracted to directly measure the thermal response of the device.
This technique enables visualization of the splitting of degenerate modes into
spatially-resolved standing waves and permits persistent optical mode editing.
Ion beam probing enables minimally perturbative, in operando imaging of
nanophotonic devices with high resolution and speed.
PMID- 29335674
TI - Noble metal nanoparticles in biosensors: recent studies and applications.
AB - The aim of this review is to cover advances in noble metal nanoparticle (MNP)
based biosensors and to outline the principles and main functions of MNPs in
different classes of biosensors according to the transduction methods employed.
The important biorecognition elements are enzymes, antibodies, aptamers, DNA
sequences, and whole cells. The main readouts are electrochemical (amperometric
and voltametric), optical (surface plasmon resonance, colorimetric,
chemiluminescence, photoelectrochemical, etc.) and piezoelectric. MNPs have
received attention for applications in biosensing due to their fascinating
properties. These properties include a large surface area that enhances
biorecognizers and receptor immobilization, good ability for reaction catalysis
and electron transfer, and good biocompatibility. MNPs can be used alone and in
combination with other classes of nanostructures. MNP-based sensors can lead to
significant signal amplification, higher sensitivity, and great improvements in
the detection and quantification of biomolecules and different ions. Some recent
examples of biomolecular sensors using MNPs are given, and the effects of
structure, shape, and other physical properties of noble MNPs and nanohybrids in
biosensor performance are discussed.
PMID- 29335678
TI - Does mental context drift or shift?
AB - Theories of episodic memory have generally proposed that individual memory traces
are linked together by a representation of context that drifts slowly over time.
Recent data challenge the notion that contextual drift is always slow and
passive. In particular, changes in one's external environment or internal model
induce discontinuities in memory that are reflected in sudden changes in neural
activity, suggesting that context can shift abruptly. Furthermore, context change
effects are sensitive to top-down goals, suggesting that contextual drift may be
an active process. These findings call for revising models of the role of context
in memory, in order to account for abrupt contextual shifts and the controllable
nature of context change.
PMID- 29335679
TI - Deep Tissue Imaging with Multiphoton Fluorescence Microscopy.
AB - We present a review of imaging deep-tissue structures with multiphoton
microscopy. We examine the effects of light scattering and absorption due to the
optical properties of biological sample and identify 1,300 nm and 1,700 nm as
ideal excitation wavelengths. We summarize the availability of fluorophores for
multiphoton microscopy as well as ultrafast laser sources to excite available
fluorophores. Lastly, we discuss the applications of multiphoton microscopy for
neuroscience.
PMID- 29335680
TI - Flows, scaling, and the control of moment hierarchies for stochastic chemical
reaction networks.
AB - Stochastic chemical reaction networks (CRNs) are complex systems that combine the
features of concurrent transformation of multiple variables in each elementary
reaction event and nonlinear relations between states and their rates of change.
Most general results concerning CRNs are limited to restricted cases where a
topological characteristic known as deficiency takes a value 0 or 1, implying
uniqueness and positivity of steady states and surprising, low-information forms
for their associated probability distributions. Here we derive equations of
motion for fluctuation moments at all orders for stochastic CRNs at general
deficiency. We show, for the standard base case of proportional sampling without
replacement (which underlies the mass-action rate law), that the generator of the
stochastic process acts on the hierarchy of factorial moments with a finite
representation. Whereas simulation of high-order moments for many-particle
systems is costly, this representation reduces the solution of moment hierarchies
to a complexity comparable to solving a heat equation. At steady states, moment
hierarchies for finite CRNs interpolate between low-order and high-order scaling
regimes, which may be approximated separately by distributions similar to those
for deficiency-zero networks and connected through matched asymptotic expansions.
In CRNs with multiple stable or metastable steady states, boundedness of high
order moments provides the starting condition for recursive solution downward to
low-order moments, reversing the order usually used to solve moment hierarchies.
A basis for a subset of network flows defined by having the same mean-regressing
property as the flows in deficiency-zero networks gives the leading contribution
to low-order moments in CRNs at general deficiency, in a 1/n expansion in large
particle numbers. Our results give a physical picture of the different
informational roles of mean-regressing and non-mean-regressing flows and clarify
the dynamical meaning of deficiency not only for first-moment conditions but for
all orders in fluctuations.
PMID- 29335681
TI - NASH-RELATED CIRRHOSIS: AN OCCULT LIVER DISEASE BURDEN.
PMID- 29335682
TI - Robust Dynamic Risk Prediction with Longitudinal Studies.
AB - Providing accurate and dynamic age-specific risk prediction is a crucial step in
precision medicine. In this manuscript, we introduce an approach for estimating
the tau-year age-specific absolute risk directly via a flexible varying
coefficient model. The approach facilitates the utilization of predictors varying
over an individual's lifetime. By using a nonparametric inverse probability
weighted kernel estimating equation, the age-specific effects of risk factors are
estimated without requiring the specification of the functional form. The
approach allows borrowing information across individuals of similar ages, and
therefore provides a practical solution for situations where the longitudinal
information is only measured sparsely. We evaluate the performance of the
proposed estimation and inference procedures with numerical studies, and make
comparisons with existing methods in the literature. We illustrate the
performance of our proposed approach by developing a dynamic prediction model
using data from the Framingham Study.
PMID- 29335683
TI - Sex Differences in Salivary Parameters of Caries Susceptibility in Healthy
Individuals.
AB - PURPOSE: To investigate salivary parameters of caries susceptibility in men and
women in order to identify potential variations due to sexual dimorphism.
MATERIALS AND METHODS: A total of 46 female and 24 male patients, aged 18-40
years, participated in this study. Unstimulated saliva was collected for the
evaluation of flow rate, pH, secretory IgA, Snyder test scores, and Streptococcus
mutans counts (confirmed by PCR assay). Statistical analysis included the Mann
Whitney, Kruskal-Wallis and Bonferroni tests, one-way ANOVA, and the Spearman
correlation at a 5% significance level, followed by a general linear model and
multiple linear regressions. RESULTS: Female participants presented lower
salivary pH values compared to males (p < 0.05), and different patterns of
correlation among salivary parameters were found in men (p < 0.05) and women (p <
0.001). When comparing the variables according to Snyder test scores in men and
women, there was a significant difference for S. mutans levels in the male group,
and for pH and IgA in the female group (p < 0.05). Gender was found to be a
predictor of salivary flow (R2 = 0.05; p < 0.05) and pH (R2 = 0.16; p < 0.001).
In the female group, multiple regression showed several predictors for salivary
flow rate, pH, IgA and Snyder test scores (p < 0.05), whereas no predictor was
found in the male group (p > 0.05). CONCLUSION: Different salivary patterns were
observed in men and women, thus the implications of such findings for caries
susceptibility require further investigation.
PMID- 29335684
TI - Association Between Self-Perceived Oral Health and Clinical Indicators.
AB - PURPOSE: To determine whether self-perceived oral health impact and satisfaction
measure oral health in the same way as do clinical indicators in adults and older
adults. MATERIALS AND METHODS: The population consisted of adult patients aged 20
to 59 years receiving care at "Juan Pablo II" Health Care Centre and older adult
patients aged 60 or more years from the home for the elderly "Virgen del Amor
Hermoso", Lima, Peru. The indices Oral Impacts on Daily Performance (OIDP) and
Oral Satisfaction Scale of 0-10 (OSS 0-10) were used to evaluate perceived impact
of and satisfaction with oral health. In addition, the following internationally
validated criteria established by the World Health Organization (WHO) were used
as clinical indicators: Decayed-Missing-Filled Teeth (DMFT) Index, O'Leary's
Hygiene Index, Community Periodontal Index, Motivation to Hygiene Index, Denture
Situation Index, Need for Denture Index, Denture Hygiene Index and Oral Mucosal
Lesion Index. RESULTS: Forty-four adults and 53 older adults participated. OIDP
showed that the greatest perceived difficulty in daily performance was "eating
and enjoying food" (adults: 77.3% and older adults: 79.2%). The OSS 0-10 showed
that among adults, 43.1% were dissatisfied, 20.5% were neutral and 36.4% were
satisfied, while among older adults, 45.3% were dissatisfied, 22.6% were neutral
and 32.1% were satisfied. A statistically significant association was found
between OSS 0-10 and 1. DMFT index in adults; 2. upper denture situation in older
adults; and 3. denture hygiene in older adults. A highly significant inverse
linear correlation was found between OIDP and OSS 0-10 in adults and older
adults. CONCLUSION: The perceived impact of oral health does not have a
demonstrable association with oral health problems when used as an instrument for
measuring oral health status, whereas perceived satisfaction with oral health has
a better association with the clinical indicators.
PMID- 29335685
TI - Can Coloured Fluoride Gel Stain Demineralised Enamel?
AB - PURPOSE: This study evaluated the colour changes of demineralized enamel after
treatment with coloured fluoride gel. MATERIALS AND METHODS: Enamel blocks
obtained from bovine incisors were submitted to artificial caries induction by pH
cycling followed by fluoride gel applications (2% sodium fluoride, pH 6.8) using
a colourless gel (control group), pink or blue gels. The enamel optical
properties were evaluated by spectrophotometry, using the CIE L*a*b* system at
baseline (sound enamel), after artificial caries induction (demineralised enamel)
and after each of the five fluoride gel applications (weekly intervals). Changes
in enamel optical properties (DeltaE) were analysed by two-way ANOVA and Tukey's
test (alpha = 0.05). RESULTS: No significant differences were found among
fluoride gels (p = 0.476) regardless of the presence of pigments in the gel.
DeltaE values were significantly different (p < 0.001) between baseline
evaluation and treated enamel (after fluoride gel application). CONCLUSION: This
in vitro study demonstrated that colour changes in enamel do not occur during
fluoride gel treatment, regardless of the presence or absence of coloured
pigments in the gel.
PMID- 29335686
TI - Synthetic Hydroxyapatite as a Biomimetic Oral Care Agent.
AB - PURPOSE: Human tooth enamel consists mostly of minerals, primarily
hydroxyapatite, Ca10(PO4)6(OH)2, and thus synthetic hydroxyapatite can be used as
a biomimetic oral care agent. This review describes the synthesis and
characterization of hydroxyapatite from a chemist's perspective and provides an
overview of its current use in oral care, with a focus on dentin
hypersensitivity, caries, biofilm management, erosion, and enamel lesions.
SOURCES: Reviews and original research papers published in English and German
were included. RESULTS: The efficiency of synthetic hydroxyapatite in occluding
open dentin tubules, resulting in a protection for sensitive teeth, has been well
documented in a number of clinical studies. The first corresponding studies on
caries, biofilm management and erosion have provided evidence for a positive
effect of hydroxyapatite either as a main or synergistic agent in oral care
products. However, more in situ and in vivo studies are needed due to the
complexity of the oral milieu and to further clarify existing results.
CONCLUSIONS: Due to its biocompatibility and similarity to biologically formed
hydroxyapatite in natural tooth enamel, synthetic hydroxyapatite is a promising
biomimetic oral care ingredient that may extend the scope of preventive
dentistry.
PMID- 29335687
TI - Structure of the Bacterial Community in Different Stages of Early Childhood
Caries.
AB - PURPOSE: To characterise in vivo the structure of bacterial communities in
decayed and sound primary teeth. MATERIALS AND METHODS: Samples of biofilms were
collected from three groups of patients with complete and exclusively primary
dentition (n = 45): G1: sound teeth (n = 15); G2: enamel lesion (n = 15); G3:
dentin lesion (n = 15). DNA was extracted (CTAB 2%) from the biofilm, the partial
16S rRNA gene was amplified with Bacteria Universal Primers (BA338fGC - UN518r)
and subjected to DGGE (denaturing gradient gel electrophoresis). Multidimensional
scaling and ANOSIM (analysis of similarity) were employed to determine the
structure of the bacterial communities. The amplicon richness was determined by
averaging amplicons, with the differences between treatments determined with
ANOVA, while means were compared using Tukey's test (p < 0.05). RESULTS: Compared
to sound teeth, a greater variety of bacterial communities was found in decayed
teeth. Despite the differences between the bacterial communities of sound teeth
and decayed teeth, the Venn diagram showed that the samples had 38 amplicons in
common. Greater amplicon richness was observed in samples of decayed teeth
(enamel: 20.5 +/- 2.7; dentin: 20.1 +/- 2.8) compared with the sound samples
(12.0 +/- 4.3) (p <0.05), indicating enhanced growth for specific groups of
bacteria on decayed teeth. CONCLUSION: Although there is less bacterial diversity
on sound than ECC-decayed teeth, the bacterial communities are very similar.
PMID- 29335688
TI - Multiple invasive cervical resorption and celiac disease: A case report.
AB - Multiple invasive cervical resorption (MICR) is a rare disease of unknown
etiology. A case of a patient with MICR of six teeth, with low vitamin D3 level
detected, is presented. Applied surgical and general treatments were only
partially effective, as they failed to stop the resorption, although the
parameters of calcium-phosphate management appreciably improved, and secondary
hyperparathyroidism was successfully resolved.
PMID- 29335689
TI - Psoriasis: A review of systemic comorbidities and dental management
considerations.
AB - OBJECTIVE: There is a growing body of evidence to substantiate that cutaneous
psoriasis is associated with an increased risk for a multitude of systemic
disorders. Although there is an extensive array of medical publications regarding
psoriasis, the dental literature has almost exclusively been focused on erythema
migrans and occasionally, with oral psoriatic mucositis, chronic periodontitis,
and psoriatic arthritis of the temporomandibular joint. This report will review
the diversity of systemic comorbidities, namely cardiovascular, neurologic,
renal, liver, gastrointestinal, pulmonary, endocrine, ocular, arthritic
(including temporomandibular joint), nail, cutaneous, and psychologic (including
suicide) disorders; neoplasia; infection; dyslipidemia; vitamin D deficiency;
substance abuse; higher mortality; and oral mucosal involvement. A discussion of
the oral and maxillofacial relevance of these comorbidities is also provided.
METHOD AND MATERIALS: The author conducted a PubMed search from 1975 through
August 2017 for articles on comorbidities associated with psoriasis. For select
topics, some relevant case reports were examined. RESULTS: A search on PubMed
yielded almost 44,000 articles on psoriasis and nearly 1,300 with the keywords
psoriasis and comorbidities. Articles selected for discussion consisted mostly of
recent systematic reviews and meta-analyses. Case reports were included when
there was a restricted number of psoriatic patients with a particular
comorbidity. CONCLUSION: When a patient presents with a history of psoriasis, the
dental practitioner should expand the medical history process to ascertain
possible correlated diseases. Information gleaned from this interview process may
prompt the attending dental clinician to seek consultation with the patient's
physician to gain greater insight to the severity of any prevailing comorbidities
and engage in discussions for possible modifications in dental management.
Knowledge of psoriatic comorbidities and their possible impact on dental care may
improve clinical outcomes.
PMID- 29335690
TI - Ni(OH)2-Fe2P hybrid nanoarray for alkaline hydrogen evolution reaction with
superior activity.
AB - It is highly attractive to develop efficient hydrogen evolution reaction (HER)
electrocatalysts under alkaline conditions. In this communication, we report the
preparation of amorphous Ni(OH)2 decorated Fe2P nanoarray on Ti mesh (Ni(OH)2
Fe2P/TM) via electrodeposition. As a 3D electrode for the hydrogen evolution
reaction, such Ni(OH)2-Fe2P/TM demonstrates superior catalytic activity.
Moreover, the as-prepares electrocatalyst requires an overpotential of only 76 mV
to drive a current density of 10 mA cm-2, which is 94 mV less than that for
Fe2P/TM. It also shows strong long-term electrochemical durability with its
catalytic activity being maintained for at least 20 h.
PMID- 29335691
TI - Size-dependent formation of membrane nanotubes: continuum modeling and molecular
dynamics simulations.
AB - Membrane nanotubes play important functional roles in numerous cell activities
such as cellular transport and communication. By exerting an external pulling
force over a finite region in a membrane patch, here we investigate the size
dependence of the membrane nanotube formation under the continuum and atomistic
modeling frameworks. It is shown that the membrane undergoes a discontinuous
shape transition as the size of the pulling region and the membrane tension
increase. A formula characterizing the nonlinear relationship between the maximum
static pulling force and pulling size is identified. During the membrane
extraction, lipids in the upper and lower leaflets exhibit different behaviors of
structural rearrangements. Moreover, our computational simulations indicate that
the steady state pulling force increases linearly with the pulling velocity as
well as the size of the pulling region.
PMID- 29335692
TI - Marine natural products.
AB - Covering: 2016. Previous review: Nat. Prod. Rep., 2017, 34, 235-294This review
covers the literature published in 2016 for marine natural products (MNPs), with
757 citations (643 for the period January to December 2016) referring to
compounds isolated from marine microorganisms and phytoplankton, green, brown and
red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms,
mangroves and other intertidal plants and microorganisms. The emphasis is on new
compounds (1277 in 432 papers for 2016), together with the relevant biological
activities, source organisms and country of origin. Reviews, biosynthetic
studies, first syntheses, and syntheses that led to the revision of structures or
stereochemistries, have been included.
PMID- 29335693
TI - Crystal structures of uranyl complexes with isobutyrate and isovalerate anions.
AB - Single crystals of Na[(UO2)(i-C3H7COO)3].0.7H2O (I), Cs[(UO2)(i-C3H7COO)3] (II)
and (NH4)[(UO2)(i-C4H9COO)3] (III) were obtained via isothermal evaporation and
their structures were solved using X-ray diffraction techniques. Even though the
ligands are branched, bulky and spatial, many carbon and hydrogen atoms are still
disordered in these crystal structures at low temperature. A new type of Na
coordination is observed for the first time for this family of compounds,
proposing high sensitivity of compound I to humidity. Depolymerization of the
metal-oxygen frameworks for the new compounds is compared with the known ones.
Coordination sequences of sodium/cesium and uranyl complexes with aliphatic
monocarboxylate ions are calculated to show different crystal-chemical function
of crystallographically independent atoms. As there are analogous compounds to
the title ones with straight-chain ligands, such groups of similar compounds with
single varying parameters are very advantageous for establishing correlations
between composition and crystal structure.
PMID- 29335694
TI - The Seventh Biennial Berry Health Benefits Symposium.
AB - Research advancing current scientific understanding of the health benefits of
berries continues to increase. The Berry Health Benefits Symposium (BHBS) is a
biennial meeting highlighting the most recent berry health benefits research from
all over the world. Pismo Beach, California was the venue for the seventh
biennial BHBS in 2017, and featured oral invited papers on heart health and
healthy aging, gut/microbiome health, brain aging, inflammation, cancer
prevention, berry special topics, technology and chemistry. These thematic health
areas, while not exhaustive, characterize the state of berry health benefits
science. The advancing field now encompasses human efficacy trials along with the
most recent animal model and cell culture work elucidating mechanisms of action.
Similar to past meetings, the research findings at the 2017 BHBS primarily
focused on blackberries, blueberries, red raspberries, black raspberries,
cranberries, and strawberries. However, research on other berry fruits, such as
chokeberry (aronia berry), cloudberry, and bilberry were also covered. The BHBS
continues to be a leading forum for interactions between scientists and berry
industry stakeholders. The cluster of papers in this issue represents a snapshot
of presentations at the 2017 BHBS, which support the positive biological effects
of berries on human health and disease risk reduction.
PMID- 29335695
TI - Synthesis of garlic skin-derived 3D hierarchical porous carbon for high
performance supercapacitors.
AB - A three-dimensional hierarchical porous carbon is synthesized via a facile
chemical activation route with garlic skin as the precursor and KOH as the
activating agent. The as-obtained carbon presents a high specific surface area of
2818 m2 g-1 and a hierarchical porous architecture containing macroporous
frameworks, mesopores (2-4 nm), and micropores (0.6-1.0 nm). As the electrode
material for a supercapacitor, due to its unique interconnected porous structure,
this garlic skin-derived carbon exhibits excellent electrochemical performance
and cycling stability. At a current density of 0.5 A g-1, the capacitance is up
to 427 F g-1 (162 F cm-3). Even at a high current density of 50 A g-1, the
capacitance can be maintained to a high value of 315 F g-1 (120 F cm-3). After
charging-discharging at a current density of 4.5 A g-1 for 5000 cycles, the
capacitance retention is as high as 94%. The results suggest that this garlic
skin-derived 3D hierarchical porous carbon is a promising electrode material for
high-performance supercapacitors.
PMID- 29335696
TI - Structurally and electronically modulated spin interaction of transient
biradicals in two photon-gated stepwise photochromism.
AB - The development of two-photon induced photochromic compounds is important for
advanced photoresponsive materials. The utilization of the long-lived transient
states or species for two-photon absorption is one of the efficient strategies to
realize the advanced photochemical behavior beyond a one-photon photochemical
reaction. We have synthesized bi-photochromic compounds composed of two
photochromic phenoxyl-imidazolyl radical complex units. The biphotochromic
compounds generate two biradical units when the two photochromic units absorb
photons with a stepwise manner. The interaction between the two biradicals
through the central bridging phenyl ring is the key feature to control the
stepwise photochromic reaction. Here, we introduced aromatic spacers in order to
modulate the distance and the dihedral angle between the biradical units. The
color and the rate of the thermal back reaction of the stepwise photochromism can
be regulated by the control of the central bridging part. These results give
important insights to develop desirable advanced photoresponsive compounds.
PMID- 29335697
TI - Photodissociation dynamics of bromoiodomethane from the first and second
absorption bands. A combined velocity map and slice imaging study.
AB - The photodissociation dynamics of bromoiodomethane (CH2BrI) have been
investigated at the maximum of the first A and second A' absorption bands, at 266
and 210 nm excitation wavelengths, respectively, using velocity map and slice
imaging techniques in combination with a probe detection of both iodine and
bromine fragments, I(2P3/2), I*(2P1/2), Br(2P3/2) and Br*(2P1/2) via (2 + 1)
resonance enhanced multiphoton ionization. Experimental results, i.e.
translational energy and angular distributions, are reported and discussed in
conjunction with high level ab initio calculations of potential energy curves and
absorption spectra. The results indicate that in the A-band, direct dissociation
through the 5A' excited state leads to the I(2P3/2) channel while I*(2P1/2) atoms
are produced via the 5A' -> 4A'/4A'' nonadiabatic crossing. The presence of Br
and Br* fragments upon excitation to the A-band is attributed to indirect
dissociation via a curve crossing between the 5A' with upper excited states such
as the 9A'. The A'-band is characterized by a strong photoselectivity leading
exclusively to the Br(2P3/2) and Br*(2P1/2) channels, which are likely produced
by dissociation through the 9A' excited state. Avoided crossings between several
excited states from both the A and A' bands entangle however the possible
reaction pathways.
PMID- 29335699
TI - Michael addition of carbonyl compounds to nitroolefins under the catalysis of new
pyrrolidine-based bifunctional organocatalysts.
AB - Novel bifunctional pyrrolidine-based organocatalysts for the asymmetric Michael
addition of carbonyl compounds to nitroolefins have been synthesised from
homoallylamines, which are easily obtained from (R)-glyceraldehyde as a chiral
precursor. Under optimal reaction conditions, these bifunctional organocatalysts
showed a high catalytic efficiency (almost quantitative yield in most cases) and
stereoselectivity in the Michael addition reactions of a variety of aldehydes (up
to 98 : 2 dr and 97% ee) and ketones (up to 98 : 2 dr and 99% ee) to
nitroolefins.
PMID- 29335698
TI - Absorbance enhancement of aptamers/GNP enables sensitive protein detection in rat
brains.
AB - An absorbance enhanced probe based on gold nanoparticles (GNPs) was proposed for
a protein assay in the cerebrospinal fluid of a rat brain. The GNPs, assembled
with two aptamers by proximity ligation, have high anti-salt properties, and good
selectivity and response toward proteins, such as interferon-gamma, in the brain.
PMID- 29335701
TI - A mononuclear manganese(iii)-hydroperoxo complex: synthesis by activating
dioxygen and reactivity in electrophilic and nucleophilic reactions.
AB - We report the synthesis of manganese(iii)-peroxo (MnIII(O2)) and manganese(iii)
hydroperoxo (MnIII(O2H)) complexes by activating dioxygen (O2) and the amphoteric
reactivity of the Mn(iii)-hydroperoxo complex in electrophilic and nucleophilic
reactions.
PMID- 29335702
TI - Ultrasmall Sn nanoparticles embedded in spherical hollow carbon for enhanced
lithium storage properties.
AB - We here report on the preparation and Li-ion battery anode application of
ultrasmall Sn nanoparticles (~5 nm) uniformly embedded in spherical hollow
carbon. The novel Sn-C composite shows a high Li-storage capacity (743 mA h g-1
at 0.5 A g-1) with unprecedentedly high cyclic stability (92.1% capacity
retention after 6000 cycles at 4 A g-1).
PMID- 29335704
TI - Photoexcited charge carrier dynamics of interconnected TiO2 nanoparticles:
evidence of enhancement of charge separation at anatase-rutile particle
interfaces.
AB - The charge carrier kinetics of hydrothermally treated TiO2 nanoparticles,
consisting of interconnected anatase and rutile crystallographic forms, was
investigated using a heterodyne transient grating technique to obtain direct
evidence of the enhancement of charge separation efficiency. We found that
surface recombination arising from trapped electrons was retarded, compared with
that of P25 TiO2 nanoparticles, with the aid of an increase of particle
interfaces. This means that the charge separation efficiency of hydrothermally
treated TiO2 nanoparticles is higher than that of P25 TiO2 nanoparticles, to
which the enhanced photocatalytic performance of the hydrothermally treated TiO2
nanoparticles could be attributed.
PMID- 29335705
TI - Synthesis of 2,5-disubstituted oxazoles via cobalt(iii)-catalyzed cross-coupling
of N-pivaloyloxyamides and alkynes.
AB - An efficient synthesis of 2,5-disubstituted oxazoles via Co(iii) catalysis is
described herein. The synthesis is achieved under mild conditions through [3+2]
cycloaddition of N-pivaloyloxyamides and alkynes. The reaction operates through
an internal oxidation pathway and features a very broad substrate scope. The one
step synthesis of natural products such as texamine and balsoxin has been
demonstrated via this protocol.
PMID- 29335709
TI - Elongated phase separation domains in spin-cast polymer blend thin films
characterized using a panoramic image.
AB - Polymer thin films with micro/nano-structures can be prepared by a solvent
evaporation induced phase separation process via spin-casting a polymer blend,
where the elongated phase separation domains are always inevitable. The striation
defect, as a thickness nonunifomity in spin-cast films, is generally coexistent
with the elongated domains. Herein, the morphologies of polymer blend thin films
are recorded from the spin-cast center to the edge in a panoramic view. The
elongated domains are inclined to appear at the ridge regions of striations with
increasing radial distance and align radially, exhibiting a coupling between the
phase separation morphology and the striation defect that may exist. We
demonstrate that the formation of elongated domains is not attributed to shape
deformation, but is accomplished in situ. A possible model to describe the
initiation and evolution of the polymer blend phase separation morphology during
spin-casting is proposed.
PMID- 29335711
TI - White Blood Cell BRCA1 Promoter Methylation Status and Ovarian Cancer Risk: A
Perspective.
PMID- 29335710
TI - Continuous-flow trapping and localized enrichment of micro- and nano-particles
using induced-charge electrokinetics.
AB - In this work, we report an effective microfluidic technique for continuous-flow
trapping and localized enrichment of micro- and nano-particles by using induced
charge electrokinetic (ICEK) phenomena. The proposed technique utilizes a simple
microfluidic device that consists of a straight microchannel and a conducting
strip attached to the bottom wall of the microchannel. Upon application of the
electric field along the microchannel, the conducting strip becomes polarized to
introduce two types of ICEK phenomena, the ICEK flow vortex and particle
dielectrophoresis, and they are identified by a theoretical model formulated in
this study to be jointly responsible for the trapping of particles over the edge
of the conducting strip. Our experiments showed that successful trapping requires
an AC/DC combined electric field: the DC component is mainly to induce
electroosmotic flow for transporting particles to the trapping location; the AC
component induces ICEK phenomena over the edge of the conducting strip for
particle trapping. The performance of the technique is examined with respect to
the applied electric voltage, AC frequency and the particle size. We observed
that the trapped particles form a narrow band (nearly a straight line) defined by
the edge of the conducting strip, thereby allowing localized particle enrichment.
For instance, we found that under certain conditions a high particle enrichment
ratio of 200 was achieved within 30 seconds. We also demonstrated that the
proposed technique was able to trap particles from several microns down to
several tens of nanometer. We believe that the proposed ICEK trapping would have
great flexibility that the trapping location can be readily varied by controlling
the location of the patterned conducting strip and multiple-location trapping can
be expected with the use of multiple conducting strips.
PMID- 29335712
TI - White Blood Cell BRCA1 Promoter Methylation Status and Ovarian Cancer Risk.
AB - Background: The role of normal tissue gene promoter methylation in cancer risk is
poorly understood. Objective: To assess associations between normal tissue BRCA1
methylation and ovarian cancer risk. Design: 2 case-control (initial and
validation) studies. Setting: 2 hospitals in Norway (patients) and a population
based study (control participants). Participants: 934 patients and 1698 control
participants in the initial study; 607 patients and 1984 control participants in
the validation study. Measurements: All patients had their blood sampled before
chemotherapy. White blood cell (WBC) BRCA1 promoter methylation was determined by
using methylation-specific quantitative polymerase chain reaction, and the
percentage of methylation-positive samples was compared between population
control participants and patients with ovarian cancer, including the subgroup
with high-grade serous ovarian cancer (HGSOC). Results: In the initial study,
BRCA1 methylation was more frequent in patients with ovarian cancer than control
participants (6.4% vs. 4.2%; age-adjusted odds ratio [OR], 1.83 [95% CI, 1.27 to
2.63]). Elevated methylation, however, was restricted to patients with HGSOC
(9.6%; OR, 2.91 [CI, 1.85 to 4.56]), in contrast to 5.1% and 4.0% of patients
with nonserous and low-grade serous ovarian cancer (LGSOC), respectively. These
findings were replicated in the validation study (methylation-positive status in
9.1% of patients with HGSOC vs. 4.3% of control participants-OR, 2.22 [CI 1.40 to
3.52]-4.1% of patients with nonserous ovarian cancer, and 2.7% of those with
LGSOC). The results were not influenced by tumor burden, storage time, or WBC
subfractions. In separate analyses of young women and newborns, BRCA1 methylation
was detected in 4.1% (CI, 1.8% to 6.4%) and 7.0% (CI, 5.0% to 9.1%),
respectively. Limitations: Patients with ovarian cancer were recruited at the
time of diagnosis in a hospital setting. Conclusion: Constitutively normal tissue
BRCA1 promoter methylation is positively associated with risk for HGSOC. Primary
Funding Source: Norwegian Cancer Society.
PMID- 29335713
TI - Risk for Arterial and Venous Thrombosis in Patients With Myeloproliferative
Neoplasms: A Population-Based Cohort Study.
AB - Background: Patients with myeloproliferative neoplasms (MPNs) are reported to be
at increased risk for thrombotic events. However, no population-based study has
estimated this excess risk compared with matched control participants. Objective:
To assess risk for arterial and venous thrombosis in patients with MPNs compared
with matched control participants. Design: Matched cohort study. Setting:
Population-based setting in Sweden from 1987 to 2009, with follow-up to 2010.
Patients: 9429 patients with MPNs and 35 820 matched control participants.
Measurements: The primary outcomes were rates of arterial and venous thrombosis.
Flexible parametric models were used to calculate hazard ratios (HRs) and
cumulative incidence with 95% CIs. Results: The HRs for arterial thrombosis among
patients with MPNs compared with control participants at 3 months, 1 year, and 5
years were 3.0 (95% CI, 2.7 to 3.4), 2.0 (CI, 1.8 to 2.2), and 1.5 (CI, 1.4 to
1.6), respectively. The corresponding HRs for venous thrombosis were 9.7 (CI, 7.8
to 12.0), 4.7 (CI, 4.0 to 5.4), and 3.2 (CI, 2.9 to 3.6). The rate was
significantly elevated across all age groups and was similar among MPN subtypes.
The 5-year cumulative incidence of thrombosis in patients with MPNs showed an
initial rapid increase followed by gentler increases during follow-up. The HR for
venous thrombosis decreased during more recent calendar periods. Limitation: No
information on individual laboratory results or treatment. Conclusion: Patients
with MPNs across all age groups have a significantly increased rate of arterial
and venous thrombosis compared with matched control participants, with the
highest rates at and shortly after diagnosis. Decreases in the rate of venous
thrombosis over time likely reflect advances in clinical management. Primary
Funding Source: The Cancer Research Foundations of Radiumhemmet,
Blodcancerfonden, the Swedish Research Council, the regional agreement on medical
training and clinical research between Stockholm County Council and Karolinska
Institutet, the Adolf H. Lundin Charitable Foundation, and Memorial Sloan
Kettering Cancer Center.
PMID- 29335714
TI - Guideline: Experts recommend a single dose of oral steroids for pain relief in
acute sore throat.
PMID- 29335715
TI - In postmenopausal women with osteoporosis, romosozumab followed by alendronate
reduced fractures vs alendronate alone.
PMID- 29335716
TI - Pooled RCTs: In postmenopausal women, hormone therapy for 6 to 7 years did not
affect mortality at 18 years.
PMID- 29335717
TI - Pooled RCTs: Reanalysis accounting for screening intensity suggests that
screening reduces prostate cancer mortality.
PMID- 29335718
TI - Adding patent foramen ovale closure to antiplatelet drugs reduced ischemic stroke
after cryptogenic stroke.
PMID- 29335719
TI - Adding patent foramen ovale closure to antiplatelet therapy reduced stroke after
cryptogenic stroke.
PMID- 29335720
TI - Review: Newer second-line drugs for diabetes are not more cost-effective than
sulfonylureas.
PMID- 29335721
TI - Review: In suspected influenza, some rapid tests have high sensitivity and high
specificity for detecting infection.
PMID- 29335722
TI - Review: In adults, contrast-enhanced CT is not linked to acute kidney injury or
mortality vs noncontrast CT.
PMID- 29335724
TI - Correction: Benefits and Harms of Intensive Blood Pressure Treatment in Adults
Aged 60 Years or Older.
PMID- 29335723
TI - Review: In primary care, CRP testing, shared decision making, and procalcitonin
reduce antibiotic prescribing for ARI.
PMID- 29335725
TI - Growth and Rupture Risk of Small Unruptured Intracranial Aneurysms.
PMID- 29335726
TI - Growth and Rupture Risk of Small Unruptured Intracranial Aneurysms.
PMID- 29335727
TI - Presence of Human Hepegivirus-1 in a Cohort of People Who Inject Drugs.
PMID- 29335728
TI - Presence of Human Hepegivirus-1 in a Cohort of People Who Inject Drugs.
PMID- 29335729
TI - Presence of Human Hepegivirus-1 in a Cohort of People Who Inject Drugs.
PMID- 29335731
TI - Changes in Hospital-Physician Affiliations in U.S. Hospitals.
PMID- 29335730
TI - Changes in Hospital-Physician Affiliations in U.S. Hospitals.
PMID- 29335732
TI - Changes in Hospital-Physician Affiliations in U.S. Hospitals.
PMID- 29335733
TI - Changes in Hospital-Physician Affiliations in U.S. Hospitals.
PMID- 29335734
TI - Two Doctors Meet.
PMID- 29335735
TI - Let the Sun Shine In! An Adventure in Open Payments.
PMID- 29335736
TI - Web Exclusives. Annals for Hospitalists Inpatient Notes - Modernizing Rounds-Why
It's Time to Redesign Our Hospital Practice.
PMID- 29335737
TI - Shedding New Light on the Magnitude of Thrombosis Risk in Patients With
Myeloproliferative Neoplasms.
PMID- 29335738
TI - Remission of Psoriasis After Treatment of Chronic Hepatitis C Virus Infection
With Direct-Acting Antivirals.
PMID- 29335739
TI - A Postzygotic SMO Mutation Caused the Original Case of Happle-Tinschert Syndrome.
PMID- 29335740
TI - Painful Papules on the Hand: A Quiz.
PMID- 29335741
TI - Methotrexate Treatment for Pityriasis Rubra Pilaris: A Case Series and Literature
Review.
AB - Treatment recommendations for pityriasis rubra pilaris (PRP) are based solely on
case reports and small case series, as to-date no randomized controlled trials
are available. We present here a case series of 3 patients and a literature
review of 28 studies treating a total of 116 patients, with the aim of providing
data regarding efficacy and safety of methotrexate in the treatment of PRP.
Methotrexate was effective in our patients; the review showed an overall response
rate of 65.5% with complete clearing in 23.3% and excellent improvement in 17.2%,
respectively. After excluding studies with other concurrent systemic therapies or
low reliability, the overall response rate increased to 90.9%, with complete
clearing in 40.9% and excellent improvement in 31.8%, respectively. Sixteen
adverse reactions, of which 11 were mild, were observed in 15 patients (12.9%).
In conclusion, the available literature supports good response rates and safety
of methotrexate in PRP.
PMID- 29335742
TI - Stand-alone Emollient Treatment Reduces Flares After Discontinuation of Topical
Steroid Treatment in Atopic Dermatitis: A Double-blind, Randomized, Vehicle
controlled, Left-right Comparison Study.
AB - Prevention of the flares is a main goal in the long-term treatment of atopic
dermatitis (AD). Therefore we investigated the efficacy of a water-in-oil
emollient, containing licochalcone A, omega-6-fatty acids, ceramide 3 and
glycerol, for prevention of the flares in adults with mild to moderately severe
AD, treated with topical steroids, that led to clearing of the inflammatory
lesions and had been discontinued prior to inclusion. The study was a 12-week,
double-blind, randomized, vehicle-controlled, left-right comparison test with the
number of relapses, defined as re-occurrence of erythema for at least 3
consecutive days, considered the primary outcome. Compared with the vehicle, the
active formulation significantly reduced the number of relapses and maintained
the barrier homeostasis of the respective arm. To the best of knowledge, this is
the first study to show prevention of the AD flares by the use of stand-alone
emollient treatment, based on comparison with the corresponding vehicle while
excluding concomitant/rescue medications.
PMID- 29335744
TI - [National Competency-Based Learning Objective Catalogue for Dental and Human
Medicine].
PMID- 29335745
TI - [Health privacy in the age of digital networks].
AB - Digitization in the health sector embodies opportunities and risks. These consist
of patient and data confidentiality. Vulnerability of data concerning integrity
and availability can lead to financial losses and to damage of the health of data
subjects. Those risks must be tackled by privacy or data protection law. For this
purpose we have the European Data Protection Regulation as a comprehensive legal
framework and a harmonizing bracket.This framework contains regulations on
consent, purpose binding and data transfer, on rights of the data subject,
technical and organizational measures and procedural arrangements. Recently,
codes of conduct and certification schemes have been added as instruments. The
frame of privacy law is completed by the law on medical products and information
security regulations.Unfortunately, German legislation did not grip the
opportunity of the European regulation to modernize, tighten and harmonize
national privacy law in the health sector. This led to a lack of clarity,
particularly because of the parallel applicability of privacy law and
professional law. Central issues - for instance concerning transparency for data
subjects, official supervision, analytics and processing for research purposes -
remain dysfunctional. The German legislation should adjust those deficits.
Corporations and the chambers for health professionals could and should also be
active for this concern.
PMID- 29335746
TI - [Cockade of the cecum in a child with acute abdominal pain].
PMID- 29335743
TI - [Prevention of cardiovascular diseases].
AB - The incidence of cardiovascular diseases can be reduced by the early detection
and targeted treatment of risk factors and subclinical forms of the disease.
Primary prevention provides several opportunities for successful interventions.
In addition to a drug-based therapy, especially life style-modifying measures,
such as physical activity, normalization of body weight, consistent nicotine
abstinence and the consideration of psychosocial aspects represent core
components of prevention programs. Healthcare data indicate that risk factors
still often remain undetected and that the full potential of risk factor
management has not yet been fully exploited at a population level. Especially
motivation of patients and adherence to therapy represent key elements of
successful prevention efforts.
PMID- 29335747
TI - Patellar resurfacing versus patellar retention in primary total knee
arthroplasty: a systematic review of overlapping meta-analyses.
AB - PURPOSE: The need of patellar resurfacing in total knee arthroplasty (TKA) is a
subject of debate. This systematic review of overlapping meta-analyses aimed to
assess and analyze current evidence regarding patellar resurfacing and non
resurfacing in TKA. METHODS: A systematic literature search was performed in
March 2017 in PubMed, CINAHL and Cochrane Library. Inclusion criteria were meta
analysis of randomized controlled trials that compared TKA with and without
patellar resurfacing considering as outcomes re-operations rate, complications,
anterior knee pain, functional scores. The quality of meta-analyses was evaluated
with AMSTAR score and the most relevant meta-analysis was determined by applying
the Jadad algorithm. RESULTS: Ten meta-analyses, published between 2005 and 2015,
were included in the systematic review. Two studies found a significantly
increased Knee Society Score in the resurfacing group. According to four meta
analyses, anterior knee pain incidence was lower in resurfacing group. Six of the
included studies described a greater risk of re-intervention in the non
resurfacing groups. The overall quality of included studies was moderate. The
most relevant meta-analysis reported no differences in functional scores and
incidence of anterior knee pain between the groups. CONCLUSIONS: Comparable
outcomes were found when comparing patellar resurfacing and non-resurfacing in
TKA. The higher risk of re-operations after non-resurfacing should be interpreted
with caution due to the methodological limitations of the meta-analyses regarding
search criteria, heterogeneity and the inherent bias of easier indication to
reoperation when the patella is not resurfaced. There is no clear superiority of
patellar resurfacing compared to patellar retention. LEVEL OF EVIDENCE: Level II,
systematic review of meta-analyses.
PMID- 29335748
TI - Hydrogel implant is as effective as osteochondral autologous transplantation for
treating focal cartilage knee injury in 24 months.
AB - PURPOSE: The treatment approach for a patient with knee joint focal cartilage
lesion is a difficult decision. To date, there has been no randomized clinical
trial involving Hydrogel (CartivaTM). This study evaluated and compared the
results of a hydrogel implant (CartivaTM) with autologous osteochondral
transplantation (AOT) for treating knee joint focal cartilage lesions. METHODS:
Thirty-eight symptomatic patients, with a focal cartilage lesion of Outerbridge
grades III or IV, were randomized into one of two groups according to the
inclusion and exclusion criteria. Group I underwent AOT, and Group II was treated
with a Hydrogel implant. Patients were evaluated preoperatively and again
postoperatively at 6, 12, and 24 months using the subjective International Knee
Documentation Committee (IKDC) scores, Visual Analog Scale for Pain (VAS Pain),
Activities of Daily Living Scale (ADLS) and Lysholm score. RESULTS: Both groups
showed significant improvements from baseline (pre-surgery) to post-surgery (6,
12, and 24 months; p < 0.05), but there was no difference between the groups.
Regarding complications, prolonged pain was observed in four patients (10.5%),
two from each group, with a regression of symptoms within 1 year. CONCLUSION: The
Hydrogel implant showed similar efficiency as the autologous osteochondral graft
for treating knee joint focal cartilage lesions. Both techniques showed
satisfactory results compared to preoperative status. The Hydrogel implant was
safe and effective, and it provided good stability and joint function at 2-year
follow-up. LEVEL OF EVIDENCE: I.
PMID- 29335750
TI - Performance drifts in two-finger cyclical force production tasks performed by one
and two actors.
AB - We explored changes in the cyclical two-finger force performance task caused by
turning visual feedback off performed either by the index and middle fingers of
the dominant hand or by two index fingers of two persons. Based on an earlier
study, we expected drifts in finger force amplitude and midpoint without a drift
in relative phase. The subjects performed two rhythmical tasks at 1 Hz while
paced by an auditory metronome. One of the tasks required cyclical changes in
total force magnitude without changes in the sharing of the force between the two
fingers. The other task required cyclical changes in the force sharing without
changing total force magnitude. Subjects were provided with visual feedback,
which showed total force magnitude and force sharing via cursor motion along the
vertical and horizontal axes, respectively. Further, visual feedback was turned
off, first on the variable that was not required to change and then on both
variables. Turning visual feedback off led to a mean force drift toward lower
magnitudes while force amplitude increased. There was a consistent drift in the
relative phase in the one-hand task with the index finger leading the middle
finger. No consistent relative phase drift was seen in the two-person tasks. The
shape of the force cycle changed without visual feedback reflected in the lower
similarity to a perfect cosine shape and in the higher time spent at lower force
magnitudes. The data confirm findings of earlier studies regarding force
amplitude and midpoint changes, but falsify predictions of an earlier proposed
model with respect to the relative phase changes. We discuss factors that could
contribute to the observed relative phase drift in the one-hand tasks including
the leader-follower pattern generalized for two-effector tasks performed by one
person.
PMID- 29335752
TI - Diagnosis and management of long-bone nonunions: a nationwide survey.
AB - PURPOSE: There is variability among surgeons on definitions regarding the degree
of bone healing of long-bone fractures. A lack of consensus may negatively affect
communication between surgeons, and lead to unintended and unwanted variability
in treatment of patients suffering from abnormal healing of long-bone fractures.
We aimed to identify differences between surgeons regarding their views on the
degree of union of long-bone fractures. METHODS: We performed a survey among 114
surgeons who worked at 11 level I trauma centers and 68 level II/III hospitals in
the Netherlands. We asked them to represent their institutional colleagues and
answer questions regarding their views on the definition, factors influencing
bone healing, clinical practice, views on scientific evidence, and the use or
need of guidelines for non-union of long-bone fractures. A total of 26 trauma
surgeons and 37 orthopedic surgeons responded (59%). RESULTS: Compared to trauma
surgeons, more orthopedic surgeons maintain 6 months as the timeframe for
classifying a fracture without healing tendencies as a non-union fracture (50 vs
70%; P = 0.019). Compared to orthopedic surgeons, trauma surgeons use the bone
scan (46 vs 19%; P = 0.027) and the PET scan (50 vs 5.4%; P < 0.001) more often,
and consider medication use to be a factor influencing bone healing more often
(92 vs 69%; P = 0.040). Furthermore, they utilize bone marrow aspiration (35 vs
11%; P = 0.029), reaming of long bones (96 vs 70%; P = 0.010), synthetic bone
substitutes (31 vs 5.4%; P = 0.012), bone morphogenetic proteins (58 vs 16%; P =
0.001), and the Diamond concept (92 vs 8.1%) more often as treatment modalities
for non-union of long-bone fractures. Surgeons agreed on that intramedullary nail
osteosynthesis was the treatment option supported by the highest level of
evidence. 80% of the respondents feel a need for a clinical guideline on the
management of long-bone non-union. CONCLUSION: There is no consensus among
surgeons on the definition, factors influencing healing, clinical practice, and
scientific evidence regarding non-union of long-bone fractures. The vast majority
of surgeons believe that their practice would benefit from (inter)national
guidelines on this topic, and efforts should be made to reduce surgeon-to-surgeon
variability in treatment recommendations and facilitate more homogenous
scientific research on non-union of long-bone fractures. LEVEL OF EVIDENCE: Level
V.
PMID- 29335751
TI - Transcranial direct current stimulation enhances foot sole somatosensation when
standing in older adults.
AB - Foot-sole somatosensation is critical for safe mobility in older adults.
Somatosensation arises when afferent input activates a neural network that
includes the primary somatosensory cortex. Transcranial direct current
stimulation (tDCS), as a strategy to increase somatosensory cortical
excitability, may, therefore, enhance foot-sole somatosensation. We hypothesized
that a single session of tDCS would improve foot-sole somatosensation, and thus
mobility, in older adults. Twenty healthy older adults completed this randomized,
double-blinded, cross-over study consisting of two visits separated by one week.
On each visit, standing vibratory threshold (SVT) of each foot and the timed-up
and-go test (TUG) of mobility were assessed immediately before and after a 20-min
session of tDCS (2.0 mA) or sham stimulation with the anode placed over C3
(according to the 10/20 EEG placement system) and the cathode over the
contralateral supraorbital margin. tDCS condition order was randomized. SVT was
measured with a shoe insole system. This system automatically ramped up, or down,
the amplitude of applied vibrations and the participant stated when they could or
could no longer feel the vibration, such that lower SVT reflected better
somatosensation. The SVTs of both foot soles were lower following tDCS as
compared to sham and both pre-test conditions [F(1,76) > 3.4, p < 0.03]. A trend
towards better TUG performance following tDCS was also observed [F(1,76) = 2.4, p
= 0.07]. Greater improvement in SVT (averaged across feet) moderately correlated
with greater improvement in TUG performance (r = 0.48, p = 0.03). These results
suggest that tDCS may enhance lower-extremity somatosensory function, and
potentially mobility, in healthy older adults.
PMID- 29335756
TI - Lead-Induced Physiological, Biochemical and Enzymatic Changes in Asplenium
scolopendrium L.
AB - The paper aims to determine the lead-induced physiological, biochemical and
enzymatic changes in Asplenium scolopendrium, which could represent biomarkers
used in environmental assessment. Of all the physiological processes,
photosynthesis and respiration were analyzed and the enzymatic and biochemical
determinations focused on catalase activity, assimilatory pigment concentration,
polyphenol content and lead presence in tissues.The stress induced by the
exposure to Pb of the species Asplenium scolopendrium determined an increase in
the carotenoid content, the catalase activity, the total polyphenol content and
also enhanced the respiration potential. No significant changes were recorded
regarding the chlorophyll content and the photosynthetic activity. The recorded
changes may be used as non-specific markers in the assessment of the impact of Pb
on plants (Asplenium scolopendrium).
PMID- 29335757
TI - Total Mercury in Squalid Callista Megapitaria squalida from the SW Gulf of
California, Mexico: Tissue Distribution and Human Health Risk.
AB - We evaluated the total Hg concentration in different tissues of squalid callista
Megapitaria squalida in order to measure Hg distribution in tissue and to
estimate human health risk. Samples were obtained by free diving in the SW Gulf
of California, Mexico. Concentrations are given on a wet weight basis. A total of
89 squalid callista specimens were obtained, presenting an average Hg
concentration of 0.07 +/- 0.04 ug g-1. There were no significant differences (p >
0.05) in Hg concentration between tissues (visceral mass = 0.09 +/- 0.08 ug g-1;
mantle = 0.06 +/- 0.07 ug g-1; muscle = 0.06 +/- 0.04 ug g-1). The low Hg values
found in squalid callista and its low risk quotient (HQ = 0.03) suggest that the
consumption of squalid callista does not represent a human health risk. However,
HQ calculated using MeHg was > 1, it which could indicate a potential risk
related to consumption of clams.
PMID- 29335749
TI - Diversity among POU transcription factors in chromatin recognition and cell fate
reprogramming.
AB - The POU (Pit-Oct-Unc) protein family is an evolutionary ancient group of
transcription factors (TFs) that bind specific DNA sequences to direct gene
expression programs. The fundamental importance of POU TFs to orchestrate
embryonic development and to direct cellular fate decisions is well established,
but the molecular basis for this activity is insufficiently understood. POU TFs
possess a bipartite 'two-in-one' DNA binding domain consisting of two
independently folding structural units connected by a poorly conserved and
flexible linker. Therefore, they represent a paradigmatic example to study the
molecular basis for the functional versatility of TFs. Their modular architecture
endows POU TFs with the capacity to accommodate alternative composite DNA
sequences by adopting different quaternary structures. Moreover, associations
with partner proteins crucially influence the selection of their DNA binding
sites. The plentitude of DNA binding modes confers the ability to POU TFs to
regulate distinct genes in the context of different cellular environments.
Likewise, different binding modes of POU proteins to DNA could trigger
alternative regulatory responses in the context of different genomic locations of
the same cell. Prominent POU TFs such as Oct4, Brn2, Oct6 and Brn4 are not only
essential regulators of development but have also been successfully employed to
reprogram somatic cells to pluripotency and neural lineages. Here we review
biochemical, structural, genomic and cellular reprogramming studies to examine
how the ability of POU TFs to select regulatory DNA, alone or with partner
factors, is tied to their capacity to epigenetically remodel chromatin and drive
specific regulatory programs that give cells their identities.
PMID- 29335758
TI - Toxicity of Diclofenac in the Fern Azolla filiculoides and the Lichen Xanthoria
parietina.
AB - This study investigated the occurrence of toxicity, expressed as damage to the
photosynthetic apparatus, in the aquatic fern Azolla filiculoides and the lichen
Xanthoria parietina following treatments with diclofenac at different
concentrations (0.1, 1, 10 and 100 mg/L) and different exposure times (24, 48, 72
and 240 h). Measurements of photosynthetic efficiency, chlorophyll content and
chlorophyll degradation indicated dose- and time-dependent toxicity, since
significant differences with control samples as well as among treatments, emerged
mainly for the highest concentration (100 mg/L) and the longest time (240 h). In
addition, also the mycobiont of the lichen X. parietina showed similar toxic
effects, expressed as ergosterol content. The absence of relevant alterations at
the lowest concentration (0.1 mg/L) suggested a very limited susceptibility of
these species to environmentally relevant levels of this pharmaceutical.
PMID- 29335759
TI - Bone-mediated anteroinferior glenohumeral instability : Current concepts.
AB - Recurrent anterior shoulder instability is commonly associated with defects of
the anterior glenoid rim. Substantial osseous defects significantly diminish the
glenohumeral stability and require a bony augmentation, either by a coracoid
transfer or free bone grafting procedure. Both reconstructive techniques have
been applied for a long time and evaluated biomechanically and clinically.
Although neither treatment option has been recognized as clearly superior, both
comprise certain advantages and disadvantages. The Latarjet technique enables a
biomechanically superior stabilization through the additional sling effect at
time zero, but constitutes an extra-anatomical procedure with a broad spectrum
and relatively high incidence of complications. Free bone grafting techniques
enable an anatomical reconstruction of the glenoid concavity, offer the advantage
of an unlimited graft size and show generally less severe and more easily
manageable complications. The indications need to be carefully considered
depending on the specific defect type, the glenoid track concept in cases of
bipolar lesions as well as the individual patient characteristics. For both
reconstructive procedures, open and arthroscopic approaches have been described
with very good results, allowing a selection based on individual surgical skills
and experience levels.
PMID- 29335760
TI - [Current aspects and new techniques in dislocation of the shoulder joint].
AB - With 12% of all injuries concerning the shoulder, acromioclavicular (AC) joint
dislocations are a common injury especially in young and active patients. The
Rockwood classification is widely accepted, which differentiates between six
types depending on the degree of injury and the vertical dislocation. Because the
classification does not adequately address the horizontal instability, its
benefits are questionable and there is currently no consensus. For this reason,
the classification and the therapy of these injuries are increasingly becoming
the subject of scientific investigations. Whereas conservative treatment for type
I and II injuries and operative treatment for type IV-VI injuries are widely
accepted, there is still no agreement in treating type III lesions. The goal of
this review article is to present the current evidence for the diagnostics,
different classifications and therapeutic possibilities.
PMID- 29335761
TI - Adjacent intervertebral space infection after lumbar fusion.
AB - BACKGROUND: Surgical site infection is a catastrophic complication after spinal
surgery, which seriously affects the progress of rehabilitation and clinical
outcome. Currently the clinical reports on spinal surgical site infections are
mostly confined to the surgical segment itself and there are few reports on
adjacent segment infections after spinal surgery. STUDY DESIGN: Case report.
OBJECTIVE: To report a clinical case with adjacent level infection after spinal
fusion. METHODS: We report the case of a 68-year-old woman who underwent
posterior lumbar 4-5 laminectomy, posterolateral fusion and internal fixation.
The patient showed signs of surgical site infection, such as surgical site pain,
high fever and increase of the inflammatory index 1 week after the operation.
Magnetic resonance imaging (MRI) confirmed the diagnosis of adjacent
intervertebral disc infection. The patient received early combined, high-dose
anti-infection treatment instead of debridement. RESULTS: After the conservative
treatment, the infection was controlled and the patient subsequently enjoyed a
normal daily life. CONCLUSION: Adjacent level infections can occur after spinal
surgery. Early diagnosis and anti-infection treatment played an important role in
the treatment of this kind of complication.
PMID- 29335763
TI - 18F-Fluorocholine PET/CT as a second line nuclear imaging technique before
surgery for primary hyperparathyroidism.
PMID- 29335764
TI - Pulmonary 18F-FDG uptake helps refine current risk stratification in idiopathic
pulmonary fibrosis (IPF).
AB - PURPOSE: There is a lack of prognostic biomarkers in idiopathic pulmonary
fibrosis (IPF) patients. The objective of this study is to investigate the
potential of 18F-FDG-PET/ CT to predict mortality in IPF. METHODS: A total of 113
IPF patients (93 males, 20 females, mean age +/- SD: 70 +/- 9 years) were
prospectively recruited for 18F-FDG-PET/CT. The overall maximum pulmonary uptake
of 18F-FDG (SUVmax), the minimum pulmonary uptake or background lung activity
(SUVmin), and target-to-background (SUVmax/ SUVmin) ratio (TBR) were quantified
using routine region-of-interest analysis. Kaplan-Meier analysis was used to
identify associations of PET measurements with mortality. We also compared PET
associations with IPF mortality with the established GAP (gender age and
physiology) scoring system. Cox analysis assessed the independence of the
significant PET measurement(s) from GAP score. We investigated synergisms between
pulmonary 18F-FDG-PET measurements and GAP score for risk stratification in IPF
patients. RESULTS: During a mean follow-up of 29 months, there were 54 deaths.
The mean TBR +/- SD was 5.6 +/- 2.7. Mortality was associated with high pulmonary
TBR (p = 0.009), low forced vital capacity (FVC; p = 0.001), low transfer factor
(TLCO; p < 0.001), high GAP index (p = 0.003), and high GAP stage (p = 0.003).
Stepwise forward-Wald-Cox analysis revealed that the pulmonary TBR was
independent of GAP classification (p = 0.010). The median survival in IPF
patients with a TBR < 4.9 was 71 months, whilst in those with TBR > 4.9 was 24
months. Combining PET data with GAP data ("PET modified GAP score") refined the
ability to predict mortality. CONCLUSIONS: A high pulmonary TBR is independently
associated with increased risk of mortality in IPF patients.
PMID- 29335765
TI - Wastewater-based tracing of doping use by the general population and amateur
athletes.
AB - The present study investigates the applicability of the chemical analysis of
wastewater to assess the use of doping substances by the general population and
amateur athletes. To this end, an analytical methodology that can identify and
quantify a list of 15 substances from the groups of anabolic steroids, weight
loss products, and masking agents in wastewater has been developed. The method
uses solid phase extraction to increase the detection sensitivity of the target
analytes, expected to be present at very low concentrations (ng L-1 range), and
decrease possible matrix interferences. Instrumental analysis is performed by
liquid chromatography coupled to high-resolution mass spectrometry, allowing data
acquisition in both full scan and tandem MS mode. The method has been
successfully validated at two concentration levels (50 and 200 ng L-1) with
limits of quantification ranging between 0.7 and 60 ng L-1, intra- and inter-day
precision expressed as relative standard deviation below 15%, procedural
recoveries between 60 and 160% and matrix effects ranging from 45 to 121%. The
stability of the analytes in wastewater was evaluated at different storage
temperatures illustrating the importance of freezing the samples immediately
after collection. The application of the method to 24-h composite wastewater
samples collected at the entrance of three wastewater treatment plants and one
pumping station while different sport events were taking place revealed the
presence in wastewater, and hence the use, of the weight loss substances
ephedrine, norephedrine, methylhexanamine, and 2,4-dinitrophenol. The use of
these stimulants was visible just prior and during the event days and in greater
amounts than anabolic steroids or masking agents. Graphical abstract Chemical
analysis of untreated wastewater reveals the use of prohibited doping substances
during amateur sport event.
PMID- 29335766
TI - Magnetofluorescent nanocomposites and quantum dots used for optimal application
in magnetic fluorescence-linked immunoassay.
AB - Magnetofluorescent nanocomposites with optimal magnetic and fluorescent
properties were prepared and characterized by combining magnetic nanoparticles
(iron oxide@polymethyl methacrylate) with fluorescent nanoparticles (rhodamine
6G@mSiO2). Experimental parameters were optimized to produce nanocomposites with
high magnetic susceptibility and fluorescence intensity. The detection of a model
biomarker (alpha-fetoprotein) was used to demonstrate the feasibility of applying
the magnetofluorescent nanocomposites combined with quantum dots and using
magnetic fluorescence-linked immunoassay. The magnetofluorescent nanocomposites
enable efficient mixing, fast re-concentration, and nanoparticle quantization for
optimal reactions. Biofunctional quantum dots were used to confirm the alpha
fetoprotein (AFP) content in sandwich immunoassay after mixing and washing. The
analysis time was only one third that required in ELISA. The detection limit was
0.2 pg mL-1, and the linear range was 0.68 pg mL-1-6.8 ng mL-1. This detection
limit is lower, and the linear range is wider than those of ELISA and other
methods. The measurements made using the proposed method differed by less than
13% from those obtained using ELISA for four AFP concentrations (0.03, 0.15,
0.75, and 3.75 ng mL-1). The proposed method has a considerable potential for
biomarker detection in various analytical and biomedical applications. Graphical
abstract Magnetofluorescent nanocomposites combined with fluorescent quantum dots
were used in magnetic fluorescence-linked immunoassay.
PMID- 29335762
TI - Targeting PSMA by radioligands in non-prostate disease-current status and future
perspectives.
AB - BACKGROUND: Prostate-specific membrane antigen (PSMA) is the up-and-coming target
for molecular imaging of prostate cancer. Despite its name, non-prostate-related
PSMA expression in physiologic tissue as well as in benign and malignant disease
has been reported in various publications. Unlike in prostate cancer, PSMA
expression is only rarely observed in non-prostate tumor cells. Instead,
expression occurs in endothelial cells of tumor-associated neovasculature,
although no endothelial expression is observed under physiologic conditions. The
resulting potential for tumor staging in non-prostate malignant tumors has been
demonstrated in first patient studies. This review summarizes the first clinical
studies and deduces future perspectives in staging, molecular characterization,
and PSMA-targeted radionuclide therapy based on histopathologic examinations of
PSMA expression. CONCLUSIONS: The non-exclusivity of PSMA in prostate cancer
opens a window to utilize the spectrum of available radioactive PSMA ligands for
imaging and molecular characterization and maybe even therapy of non-prostate
disease.
PMID- 29335767
TI - Atrial fibrillation and MPNs.
PMID- 29335769
TI - An adolescent presenting with acquired acute renal damage: Questions.
PMID- 29335770
TI - An adolescent presenting with acquired acute renal damage: Answers.
PMID- 29335768
TI - CTLA-4 polymorphisms: influence on transplant-related mortality and survival in
children undergoing allogeneic hematopoietic stem cell transplantation.
AB - PURPOSE: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative
approach for a variety of hematological diseases; however, it is still associated
with substantial morbidity and mortality. Transplant-related mortality (TRM)
after HSCT depends mainly on the toxicity of the conditioning regimen,
infections, and graft-versus-host disease. The purpose of this study was to
identify the association between CTLA-4 single nucleotide polymorphisms and TRM
in children undergoing allogeneic HSCT. METHODS: 153 donors and 153 children with
acute lymphoblastic leukemia, acute myeloid leukemia or juvenile myelomonocytic
leukemia who had undergone allogeneic HSCT were genotyped of CTLA-4 gene for
rs3087243 (CT60G>A), rs231775 (+ 49 A>G) and rs4553808 using TaqMan real-time
polymerase chain reaction. RESULTS: We observed a significant association between
the donor's CLTA-4 genotype of rs3087243 and TRM in children undergoing
allogeneic HSCT. Genotype AG was found in 78 donors (51%), GG in 44 donors (29%)
and 31 donors (20%) were homozygous for AA. 30 patients died as a result of
transplant-related causes. Interestingly, we observed a significantly reduced TRM
in children who were transplanted from a donor with the CTLA-4 genotype GG in
comparison to genotype AG or AA (9 versus 19 versus 36%, P = 0.013). In addition,
we found significant differences of event-free survival (EFS) depending on the
donor's genotype. The EFS was 64, 46 or 32% if the patient was transplanted from
a donor with CTLA-4 genotype GG, AG or AA, respectively (P = 0.043). In
multivariate analysis, CTLA-4 genotype of rs3087243 was an independent risk
factor for TRM (P = 0.011) and EFS (P = 0.035). CONCLUSION: This study provides
first evidence that the CTLA-4 polymorphisms are significant risk factors for TRM
and survival in children undergoing allogeneic HSCT and should be evaluated in
further trials.
PMID- 29335772
TI - Investigation on the correlation between energy deposition and clustered DNA
damage induced by low-energy electrons.
AB - This study presents the correlation between energy deposition and clustered DNA
damage, based on a Monte Carlo simulation of the spectrum of direct DNA damage
induced by low-energy electrons including the dissociative electron attachment.
Clustered DNA damage is classified as simple and complex in terms of the
combination of single-strand breaks (SSBs) or double-strand breaks (DSBs) and
adjacent base damage (BD). The results show that the energy depositions
associated with about 90% of total clustered DNA damage are below 150 eV. The
simple clustered DNA damage, which is constituted of the combination of SSBs and
adjacent BD, is dominant, accounting for 90% of all clustered DNA damage, and the
spectra of the energy depositions correlating with them are similar for different
primary energies. One type of simple clustered DNA damage is the combination of a
SSB and 1-5 BD, which is denoted as SSB + BD. The average contribution of SSB +
BD to total simple clustered DNA damage reaches up to about 84% for the
considered primary energies. In all forms of SSB + BD, the SSB + BD including
only one base damage is dominant (above 80%). In addition, for the considered
primary energies, there is no obvious difference between the average energy
depositions for a fixed complexity of SSB + BD determined by the number of base
damage, but average energy depositions increase with the complexity of SSB + BD.
In the complex clustered DNA damage constituted by the combination of DSBs and BD
around them, a relatively simple type is a DSB combining adjacent BD, marked as
DSB + BD, and it is of substantial contribution (on average up to about 82%). The
spectrum of DSB + BD is given mainly by the DSB in combination with different
numbers of base damage, from 1 to 5. For the considered primary energies, the DSB
combined with only one base damage contributes about 83% of total DSB + BD, and
the average energy deposition is about 106 eV. However, the energy deposition
increases with the complexity of clustered DNA damage, and therefore, the
clustered DNA damage with high complexity still needs to be considered in the
study of radiation biological effects, in spite of their small contributions to
all clustered DNA damage.
PMID- 29335771
TI - Risk perception of heat waves and its spatial variation in Nanjing, China.
AB - The intensity, frequency, and duration of heat waves are expected to increase
with climate change. In this study, we found a significant difference of public
perceived effects of heat waves and trust in government among urban, suburban,
and rural districts. Rural residents had a significant higher effect perception
than urbanites and also showed stronger willingness to have medical insurance or
regular physical examinations. Meanwhile, suburban residents had the lowest trust
perception in government among these three districts, which may be due to
suburban districts' unique social structure and complex social issues. Besides,
we assessed the relationship between the factor effect and demographic variables.
The results showed that urban respondents' effect perception was significantly
related to heat wave experiences. Suburban respondents' effect perception was
significantly related to age, income, and heat wave experiences. And rural
respondents' effect perception was significantly related to income and chronic
diseases. Based on our results, much more attention needs to be paid to rural
districts. The government should strengthen infrastructure construction such as
cooling centers, improve emergency response plans and mechanisms, and increase
reserves of emergency supplies in rural districts. Also, targeted risk
communication is of the equal importance to aid the policy-makers improving the
relationship with the public and regaining the public's trust and support.
PMID- 29335773
TI - Effects of combining ergonomic interventions and motor control exercises on
muscle activity and kinematics in people with work-related neck-shoulder pain.
AB - PURPOSE: This study compared the effects of "Ergomotor" intervention and
conventional physiotherapy, on influencing the motor control in the neck-shoulder
region in people with work-related neck-shoulder pain (WRNSP). METHODS: 101
patients (age range 20-54 years) diagnosed with chronic WRNSP were randomized
into control (CO) group (n = 50) and Ergomotor (EM) group (n = 51). Each group
received a 12-week intervention. Participants in CO group received treatment for
pain relief and general exercises. EM group received individualized motor control
training and advice of ergonomic modifications at their workplaces. RESULTS: At
post-intervention, EM group showed significant reduction of bilateral upper
trapezius muscle activity during active neck movements (left: 40-35%, right: 35
27%) and functional tasks such as lifting a weight forward-backward (left: 31
21%, right: 22-14%) and upward-downward (left: 26-23%, right: 20-13%). Cervical
erector spinae also showed significant decrease in muscle activity during some
phases of the functional tasks (left: 13-6%, right: 10-2%). In contrast, CO group
did not show such changes in muscle activity at post-intervention. EM group also
showed significant increase in movement velocity and acceleration during active
neck movements in all directions (from 18 to 31%), while CO group only showed
significant increase in movement velocity in some directions. Both groups
reported significant but similar reduction in pain scores, at post-intervention
and 1-year follow-up. CONCLUSIONS: The present results provided some evidence to
support the positive and sustainable benefits of integrating motor control
training into the workplace postures and motions.
PMID- 29335774
TI - Genomic trade-offs: are autism and schizophrenia the steep price of the human
brain?
AB - Evolution often deals in genomic trade-offs: changes in the genome that are
beneficial overall persist even though they also produce disease in a subset of
individuals. Here, we explore the possibility that such trade-offs have occurred
as part of the evolution of the human brain. Specifically, we provide support for
the possibility that the same key genes that have been major contributors to the
rapid evolutionary expansion of the human brain and its exceptional cognitive
capacity also, in different combinations, are significant contributors to autism
and schizophrenia. Furthermore, the model proposes that one of the primary genes
behind this trade-off may not technically be "a gene" or "genes" but rather are
the highly duplicated sequences that encode the Olduvai protein domain family
(formerly called DUF1220). This is not an entirely new idea. Others have proposed
that the same genes involved in schizophrenia were also critical to the rapid
expansion of the human brain, a view that has been expressed as "the same 'genes'
that drive us mad have made us human". What is new is that a "gene", or more
precisely a protein domain family, has been found that may satisfy these
requirements.
PMID- 29335775
TI - A new genus, Planticonsortium (Mucoromycotina), and new combination (P. tenue),
for the fine root endophyte, Glomus tenue (basionym Rhizophagus tenuis).
AB - In 1977, the fine root endophyte, originally named Rhizophagus tenuis, was
transferred into the genus Glomus as G. tenue, thus positioning the species with
all other known arbuscular mycorrhizal fungi (Glomeromycota, Glomeromycotina).
Recent molecular evidence, however, places it in a different subphylum,
Mucoromycotina in the Mucoromycota. No suitable genus exists in the
Mucoromycotina to accommodate G. tenue, so it is moved to Planticonsortium gen.
nov. as P. tenue comb. nov.
PMID- 29335776
TI - MIGS: therapeutic success of combined Xen Gel Stent implantation with cataract
surgery.
AB - PURPOSE: Glaucoma, a common disease in the elderly population, is frequently
coexistent with cataract. While the combination of filtration surgery and
cataract surgery is a challenging topic with limited success, minimal invasive
glaucoma surgery (MIGS), such as Xen Gel Stents, seems to provide promising
results. The aim of this study was to investigate the complete and qualified
therapeutic success of Xen Gel Stent implantation with (XenPhaco) and without
cataract surgery. METHODS: One hundred and eleven open-angle glaucoma eyes
underwent implantation of Xen45 Gel Stent (AqueSys, Inc.) with or without
cataract operation. Complete therapeutic success was defined as target
intraocular pressure (IOP) < 18 mmHg at any time point within 6 months of follow
up without local antiglaucomatous therapy or further surgical interventions.
Qualified success was defined as target IOP <18 mmHg with additional 1-2 local
antiglaucomatous eye drops. Failure included all cases with the necessity of at
least three local antiglaucomatous eye drops or additional glaucoma surgery.
RESULTS: Combined implantation of Xen Gel Stent with cataract surgery was
performed in 30 eyes and stand-alone Xen Gel Stent implantation was performed in
81 eyes. A complete therapeutic success was achieved in 46.9% of single Xen Gel
Stent implantation, whereas 53.3% was reached with combined XenPhaco. Qualified
success was seen in 2.5% in the eyes of the single Xen Gel Stent implantation
group and in 3.3% of the combined surgery group. Therapeutic failure rate was
49.4% in the stand-alone group vs 46.7% in the combined group. Data were not
significantly different for group and subgroup analyses. CONCLUSIONS: Complete
and qualified therapeutic success is similar for the combination of Xen Gel Stent
implantation with and without cataract surgery in open-angle glaucoma patients.
MIGS using Xen Gel Stent can be recommended in situations if glaucoma surgery is
indicated besides coexisting cataract.
PMID- 29335778
TI - Hippocampal area CA2: properties and contribution to hippocampal function.
AB - This review focuses on area CA2 of the hippocampus, as recent results have
revealed the unique properties and surprising role of this region in encoding
social, temporal and contextual aspects of memory. Originally identified and
described by Lorente de No, in 1934, this region of the hippocampus has unique
intra-and extra-hippocampal connectivity, sending and receiving input to septal
and hypothalamic regions. Recent in vivo studies have indicated that CA2
pyramidal neurons encode spatial information during immobility and play an
important role in the generation of sharp-wave ripples. Furthermore, CA2 neurons
act to control overall excitability in the hippocampal network and have been
found to be consistently altered in psychiatric diseases, indicating that normal
function of this region is necessary for normal cognition. With its unique role,
area CA2 has a unique molecular profile, interneuron density and composition.
Furthermore, this region has an unusual manifestation of synaptic plasticity that
does not occur post-synaptically at pyramidal neuron dendrities but through the
local network of inhibitory neurons. While much progress has recently been made
in understanding the large contribution of area CA2 to social memory formation,
much still needs to be learned.
PMID- 29335777
TI - Fully automatic CT-histogram-based fat estimation in dead bodies.
AB - Post-mortem body cooling is the foundation of temperature-based death time
estimations (TDE) in homicide cases. Forensic science generally provides two
types of p.m. body cooling models, the phenomenological and the physical models.
Since both of them have to implement important individual parameters like the
quantity of abdominal fat explicitly or implicitly, a more exact quantification
and localization of abdominal fat is a desideratum in TDE. Particularly for the
physical models, a better knowledge of the abdominal fat distribution could lead
to relevant improvements in TDEs. Modern imaging methods in medicine like
computed tomography (CT) are opening up the possibility to register the quantity
and spatial distribution of body fat in individual cases with unprecedented
precision. Since a CT-scan of an individual's abdominal region can comprise 1000
slices as an order of magnitude, it is evident that their evaluation for body fat
quantification and localization needs fully automated algorithms. The paper at
hand describes the development and validation of such an algorithm called "CT
histogram-based fat estimation and quasi-segmentation" (CFES). The approach can
be characterized as a weighted least squares method dealing with the gray value
histogram of single CT-slices only. It does not require any anatomical a priori
information nor does it perform time-consuming feature detection on the CT
images. The processing result consists in numbers quantifying the amount of
abdominal body fat and of muscle-, organ-, and connective tissue. As a by
product, CFES generates a quasi-segmentation of the slices processed
differentiating fat from muscle-, organ-, and connective tissue. The tool is
validated on synthetic data and on CT-data of a special phantom. It was also
applied on a CT-scan of a dead body, where it produced anatomically plausible
results.
PMID- 29335779
TI - Equine neutrophils and their role in ischemia reperfusion injury and lung
inflammation.
AB - Horses are susceptible to a multitude of inflammatory conditions that are
characterized by a strong neutrophilic response. Here, we review basic equine
neutrophil biology and explore the role of neutrophils in inflammatory conditions
with emphasis on intestinal ischemia and reperfusion injury and lung
inflammation. In addition, unique aspects of equine neutrophil biology have been
highlighted. Neutrophils comprise the highest proportion of circulating white
blood cells in equine blood. The concentration of circulating equine neutrophils
is a primary indicator of systemic inflammation. Additionally, equine neutrophils
exposed to various stimulants develop "toxic" changes characterized as
cytoplasmic basophilia, presence of Dohle bodies, cytoplasmic vacuolation and
toxic granulation. In contrast to human neutrophils, equine neutrophils fail to
undergo chemotaxis in response to the peptide N-formyl-methionyl-leucyl
phenylalanine and are dependent on the addition of arachidonic acid due to
reduced activity of phospholipase A2 to synthesize leukotrienes as part of the
arachidonic acid pathway. Understanding the biologic function of neutrophils in
horses is integral to developing methods to modulate inflammation associated with
ischemia reperfusion injury and lung disease.
PMID- 29335781
TI - Peripartum events associated with severe neurologic morbidity and mortality among
acidemic neonates.
AB - PURPOSE: To identify peripartum events that may predict the development of short
term neurologic morbidity and mortality among acidemic neonates. METHODS:
Retrospective case-control study conducted at a single-teaching hospital on data
from January 2010 to December 2015. The study cohort group included all acidemic
neonates (cord artery pH <= 7.1) born at >= 34 weeks. Primary outcome was a
composite including any of the following: neonatal encephalopathy, convulsions,
intra-ventricular hemorrhage, or neonatal death. The study cohort was divided to
the cases group, i.e., acidemic neonates who had any component of the primary
outcome, and a control group, i.e., acidemic neonates who did not experience any
component of the primary outcome. RESULTS: Of all 24,311 neonates born >= 34
weeks during the study period, 568 (2.3%) had a cord artery pH <= 7.1 and
composed the cohort study group. Twenty-one (3.7%) neonates composed the cases
group. Multivariate logistic regression analysis revealed that cases were
significantly more likely to have experienced placental abruption (OR 18.78; 95%
CI 5.57-63.26), born <= 2500 g (OR 13.58; 95% CI 3.70-49.90), have meconium (OR
3.80; 95% CI 1.20-11.98) and cord entanglement (OR 5.99; 95% CI 1.79-20.06). The
probability for developing the composite outcome rose from 3.7% with isolated
acidemia to 97% among neonates who had all these peripartum events combined with
intrapartum fetal heart rate tracing category 2 or 3. CONCLUSION: Neonatal
acidemia carries a favorable outcome in the vast majority of cases. In
association with particular antenatal and intrapartum events, the short-term
outcome may be unfavorable.
PMID- 29335780
TI - A comparison of semi-automated volumetric vs linear measurement of small
vestibular schwannomas.
AB - OBJECTIVE: Accurate and precise measurement of vestibular schwannoma (VS) size is
key to clinical management decisions. Linear measurements are used in routine
clinical practice but are prone to measurement error. This study aims to compare
a semi-automated volume segmentation tool against standard linear method for
measuring small VS. This study also examines whether oblique tumour orientation
can contribute to linear measurement error. STUDY DESIGN: Experimental comparison
of observer agreement using two measurement techniques. SETTING: Tertiary skull
base unit. PARTICIPANTS: Twenty-four patients with unilateral sporadic small (<
15 mm maximum intracranial dimension) VS imaged with 1 mm-thickness T1-weighted
Gadolinium enhanced MRI. MAIN OUTCOME MEASURES: (1) Intra and inter-observer
intraclass correlation coefficients (ICC), repeatability coefficients (RC), and
relative smallest detectable difference (%SDD). (2) Mean change in maximum linear
dimension following reformatting to correct for oblique orientation of VS.
RESULTS: Intra-observer ICC was higher for semi-automated volumetric when
compared with linear measurements, 0.998 (95% CI 0.994-0.999) vs 0.936 (95% CI
0.856-0.972), p < 0.0001. Inter-observer ICC was also higher for volumetric vs
linear measurements, 0.989 (95% CI 0.975-0.995) vs 0.946 (95% CI 0.880-0.976), p
= 0.0045. The intra-observer %SDD was similar for volumetric and linear
measurements, 9.9% vs 11.8%. However, the inter-observer %SDD was greater for
volumetric than linear measurements, 20.1% vs 10.6%. Following oblique
reformatting to correct tumour angulation, the mean increase in size was 1.14 mm
(p = 0.04). CONCLUSION: Semi-automated volumetric measurements are more
repeatable than linear measurements when measuring small VS and should be
considered for use in clinical practice. Oblique orientation of VS may contribute
to linear measurement error.
PMID- 29335782
TI - Association of endogenous circulating sex steroids and condition-specific quality
of life domains in postmenopausal women with pelvic floor disorders.
AB - OBJECTIVE: To examine the relationship between endogenous sex steroids and
various condition-specific quality of life domains in postmenopausal women with
pelvic floor disorders. We hypothesized that woman with lowest androgen and
estradiol concentrations would report worse scores of quality of life domains.
METHODS: Forty-six women with pelvic organ prolapse (POP) and 47 cases with
stress urinary incontinence (SUI) answered the validated pelvic floor
questionnaire and underwent serum sex steroid measurement. A multivariate
logistic regression model was used to determine the association between
subjective outcome parameters and serum hormonal levels after adjusting for
confounders. RESULTS: Univariate analysis revealed a strong inverse correlation
between serum estradiol level (E2) and prolapse domain score (correlation
coefficient = 0.005) as well as a significant positive correlation between SHBG
level and prolapse domain score (correlation coefficient = 0.019) in cases with
POP. Furthermore, the sex domain score showed a significant negative correlation
with the androstendion (correlation coefficient = 0.020), DHEAS (correlation
coefficient = 0.046) and testosterone level (correlation coefficient = 0.032) in
the POP group. In the multivariate model, high serum SHBG (CI: 0.007-0.046)
remained independently associated with worse scores in the prolapse domain and
low serum DHEAS (CI: - 0.989 to 1.320) persisted as a significant predictor for a
worse score in the sex domain. Regarding SUI cases, no association was noted
between serum hormonal levels and quality of life related pelvic floor domains
(correlation coefficient > 0.05). CONCLUSION: Our results suggest that pelvic
floor related quality of life might also be affected by endogenous sex steroids
in POP, but not in SUI cases.
PMID- 29335783
TI - Maternal and neonatal omentin-1 levels in gestational diabetes.
AB - PURPOSE: To evaluate the effect of gestational diabetes on omentin-1 in maternal
and cord plasma. As a potent mediator of insulin resistance, Omentin-1, an
adipokine derived from human adipose and placental tissue, may be an important
player in the pathophysiology of gestational diabetes. METHODS: This was a
prospective case-control study. The study included 96 women with gestational
diabetes and 96 pregnant women without. Omentin-1 was measured at the time of the
oral glucose tolerance test, at 32 weeks in maternal plasma and right after
delivery in umbilical cord blood by ELISA assay. RESULTS: Over a period of 2
years, 200 patients were enrolled. Omentin-1 levels did not significantly differ
between both groups throughout the pregnancy: omentin-1 levels were 157 +/- 83
ng/ml in women with gestational diabetes and 158 +/- 93 ng/ml in women without
gestational diabetes (p = 0.94) at time of the oral glucose tolerance test and
118 +/- 77 ng/ml in women with diabetes and 150 +/- 89 ng/ml in women without (p
= 0.12) at 32 weeks, respectively. Both groups showed a decrease in omentin-1
levels throughout pregnancy, with a more pronounced decrease in diabetic women
(13 +/- 53 versus 4 +/- 48 ng/ml; p = 0.5). Neonatal omentin-1 levels were
significantly lower in offspring of diabetic mothers: 106 +/- 61 versus 134 +/-
45 ng/ml (p = 0.03). CONCLUSIONS: There was no significant difference in omentin
1 levels between healthy and diabetic mothers throughout the pregnancy. However,
we found significantly lower omentin-1 levels in offspring of diabetic mothers.
This may indicate a risk for the development of insulin resistance in later life.
PMID- 29335784
TI - Clinical significance of miRNA-21, -103, -129, -150 in serous ovarian cancer.
AB - PURPOSE: We aimed to compare expression levels of miRNA-21, -103, -129, -150 in
primary tumour tissues and its omental metastases from patients operated for
advanced ovarian serous cancer. Expression levels of selected miRNAs were
correlated with clinicopathological features, including chemosensitivity and
survival. METHODS: We performed total RNA extraction from archival formalin-fixed
paraffin-embedded tissue samples of primary serous ovarian cancer and omental
metastases. The study included 48 patients with advanced ovarian cancer. The
reference group consisted of 48 normal ovarian tissue samples. We performed cDNA
synthesis, real time polymerase chain reaction and assessed relative expression
of selected miRNAs. RESULTS: Samples derived from serous ovarian cancer were
characterized by higher expression levels of miRNA-150 in comparison to omental
metastases (p = 0.045). Furthermore, we observed that shorter progression free
survival was associated with lower levels of miRNA-150 in metastatic tissues. We
did not find similar relationships for other miRNAs. CONCLUSIONS: MiRNA-150 may
potentially serve as a prognostic factor in advanced ovarian cancer. However,
further studies are required to clearly confirm such hypothesis.
PMID- 29335785
TI - Heterologous expression of rice 9-cis-epoxycarotenoid dioxygenase 4 (OsNCED4) in
Arabidopsis confers sugar oversensitivity and drought tolerance.
AB - BACKGROUND: The 9-cis-epoxycarotenoid dioxygenases OsNCED4 was cloned from rice
in conjunction with OsNCED 1-3 and 5, of which 3 has been shown to function in
ABA biosynthesis and alteration of leaf morphology. In higher plants, NCEDs have
been shown to be key enzymes controlling ABA biosynthesis and belong to a
differentially expressed gene family. Aside from OsNCED3, it remains largely
unknown if other OsNCED genes are involved in ABA biosynthesis in rice. Thus,
transgenic Arabidopsis plants overexpressing OsNCED4 were generated in the
129B08/nced3 mutant background to explore OsNCED4 function in ABA biosynthesis.
RESULTS: Heterologous expression of OsNCED4 in Arabidopsis increased ABA levels
and altered plant size and leaf shape, delayed seed germination, caused sugar
oversensitivity in post-germination growth, and enhanced tolerance to drought.
The native OsNCED3 and OsNCED4 promoters were expressed in an overlapping pattern
in rice seeds and young seedlings, suggesting possible functional redundancy
between OsNCED3 and OsNCED4. At the one-leaf stage, similar regulation of OsNCED3
and OsNCED4 gene expression in roots or leaves in response to moderate salt
stress (150 mM NaCl) was observed. CONCLUSION: Like OsNCED3, OsNCED4 is
functionally active in ABA biosynthesis in rice. OsNCED3 and OsNCED4 might play
redundant roles in controlling ABA biosynthesis in rice, as suggested by GUS
staining assay, but this should be further analyzed through complementation of
rice NCED knockout mutants.
PMID- 29335786
TI - Anti-inflammatory and antiplatelet effects of non-vitamin K antagonist oral
anticoagulants in acute phase of ischemic stroke patients.
AB - BACKGROUND: Recently, non-vitamin K antagonist oral anticoagulants such as direct
thrombin and direct factor Xa inhibitors have been prescribed for prevention of
embolic stroke. While in Japan, argatroban, also a direct thrombin inhibitor, is
available for the treatment of atherothrombotic stroke patients. This study aimed
to explore whether there is any differences between direct thrombin and direct
factor Xa inhibitors regarding the inhibiting effect against thrombogenesis in
the clinical setting of acute ischemic stroke. METHODS: Acute ischemic stroke
patients newly prescribed anti-thrombotic agents were consecutively screened, and
44 patients with single medicine were enrolled (median 72.0 years-old). Blood
samples were obtained at 1 and 2 weeks after the medication started. The extent
of anticoagulation activity, inflammatory markers and platelet aggregation were
assessed. Patients with antiplatelets were used as control. RESULTS: Prescribed
antithrombotics were dabigatran (group D: n = 12), apixaban (group A: n = 14) and
antiplatelet agents (group P: n = 18). Prevalence of stroke risks and
anticoagulation activity were not different between groups D and A. The
alteration of inflammatory markers in a week in the group A showed similar trend
to those in the group P. The group D presented relatively lower amount of high
sensitive C-reactive protein and higher amount of pentraxin-3 compared with
groups A and P. While 88.9% of group P patients showed decreased platelet
aggregation activity with adenosine diphosphate, 55.6% of group D and 40.0% of
group A presented the inhibition of platelet aggregation activity. CONCLUSIONS:
Even in acute ischemic stroke patients, both apixaban and dabigatran equally
showed the anticoagulation activity. The reduction of inflammatory response might
be prominent in apixaban, whereas the inhibition of platelet aggregation activity
might be evident in dabigatran.
PMID- 29335787
TI - Synthesis of Water-Soluble Antimony Sulfide Quantum Dots and Their Photoelectric
Properties.
AB - Antimony sulfide (Sb2S3) has been applied in photoelectric devices for a long
time. However, there was lack of information about Sb2S3 quantum dots (QDs)
because of the synthesis difficulties. To fill this vacancy, water-soluble Sb2S3
QDs were prepared by hot injection using hexadecyltrimethylammonium bromide
(CTAB) and sodium dodecyl sulfate (SDS) mixture as anionic-cationic surfactant,
alkanol amide (DEA) as stabilizer, and ethylenediaminetetraacetic acid (EDTA) as
dispersant. Photoelectric properties including absorbing and emission were
characterized by UV-Vis-IR spectrophotometer and photoluminescence (PL)
spectroscopic technique. An intensive PL emission at 880 nm was found, indicating
Sb2S3 QDs have good prospects in near-infrared LED and near-infrared laser
application. Sb2S3 QD thin films were prepared by self-assembly growth and then
annealed in argon or selenium vapor. Their band gaps (E g s) were calculated
according to transmittance spectra. The E g of Sb2S3 QD thin film has been found
to be tunable from 1.82 to 1.09 eV via annealing or selenylation, demonstrating
the good prospects in photovoltaic application.
PMID- 29335788
TI - Over-expression of a grafting-responsive gene from hickory increases abiotic
stress tolerance in Arabidopsis.
AB - KEY MESSAGE: A grafting response gene CcPIP1;2 was cloned from hickory plant,
further functional characterization of the gene for water transport activity and
abiotic stress tolerances were carried out through heterologous expression in
Xenopus and Arabidopsis. Plasma membrane intrinsic proteins (PIPs) are
multifunctional channel proteins belonging to the membrane intrinsic protein
(MIP) family. In this study, a grafting-responsive gene from hickory (CcPIP1;2)
was cloned and functionally characterized. Application of non-selective water
inhibitors (HgCl2 and phloretin) led to the death of grafted hickory plants at 30
days after grafting (DAG). Furthermore, the transcript accumulation of the
selected CcPIP1;2 gene was gradually decreased from 0 to 14 DAG in the grafted
samples under inhibitor treatment conditions. Transient expression analysis of
the GFP-CcPIP1;2 fusion protein showed that CcPIP1;2 was located at plasma
membrane. Heterologous expression of CcPIP1;2 protein in the Xenopus oocyte
system helped the access of water into the cells. Over-expression of CcPIP1;2 in
Arabidopsis improved the percentage of seed germination when the seeds were grown
in H2O2-, ABA-, and mannitol-containing media, but had no effect when grown in
the salt containing media. CcPIP1;2 transgenic plants grew better under drought
conditions. The expression of various ABA-related stress marker genes as well as
cell wall expansin marker genes was significantly higher in CcPIP1;2 over
expression Arabidopsis lines than in the wild type (WT).
PMID- 29335789
TI - First record of Trypanosoma dionisii of the T. cruzi clade from the Eastern bent
winged bat (Miniopterus fuliginosus) in the Far East.
AB - Chiropteran mammals worldwide harbour trypanosomes (Euglenozoa: Kinetoplastea:
Trypanosomatida) of the subgenus 'Schizotrypanum' in the classical sense.
Latterly, these trypanosomes have been referred to as members of the 'Trypanosoma
cruzi clade' as their phylogenetic relationships, structure and life cycle
conform to T. cruzi, parasitising various terrestrial mammals as well as humans
in Latin America. Little is known, however, about the trypanosome species in
Asian bats. During a survey on Borrelia spp. in the Eastern bent-winged bat
(Miniopterus fuliginosus) living in a cave in Wakayama Prefecture, Japan,
incidental proliferation of trypanosomes was detected in two of 94 haemocultures.
Squat or slender trypanosomes that proliferated in the cultures were 7.5-20.5 MUm
in length between both body ends and 1.0-3.8 MUm in width with/without free
flagella up to 14.5 MUm (n = 29). The nucleotide sequences of the small subunit
ribosomal RNA gene (SSU rDNA; 2176 bp), large subunit ribosomal RNA gene (1365
bp) and glycosomal glyceraldehyde-3-phosphate dehydrogenase gene (gGAPDH; 843 bp)
of the present isolates were characterized to clarify their molecular
phylogenetic position in T. cruzi-like trypanosomes. The newly obtained SSU rDNA
and gGAPDH nucleotide sequences showed the highest identities with Brazilian and
European isolates of Trypanosoma dionisii of the T. cruzi clade, ranging between
99.4 and 99.7% or between 95.6 and 99.3% identities, respectively. Although
multiple T. dionisii isolates from the North and South American continents showed
the closest molecular genetic relatedness to the present Far East isolates, only
short SSU rDNA segments of the former isolates were deposited. Therefore, a
definitive conclusion cannot be made until full nucleotide sequencing of at least
the American isolates' SSU rDNA is available. This is the first confirmation of a
Far East distribution of T. dionisii, demonstrating a wide geographical
distribution of the species in the Eurasian and American continents with a
limited nucleotide variation.
PMID- 29335790
TI - Echinococcus multilocularis (Cestoda, Cyclophyllidea, Taeniidae): origin,
differentiation and functional ultrastructure of the oncospheral tegument and
hook region membrane.
AB - Both the oncospheral tegument and the hook region membrane (HRM) of Echinococcus
multilocularis hexacanths originate from a syncytial binucleate complex that
appears in the early stage of morphogenesis and organogenesis of the hexacanth
larva. The primordium of this binucleate complex forms a binucleate syncytial cap
or "calotte" situated beneath the inner envelope at one pole of the developing
embryo. During oncospheral differentiation, the binucleate perikaryon of the
syncytial cap is sunk progressively deeper into the central part of the embryo,
but remains always connected with the distal cytoplasm by a tendrillar
cytoplasmic connection or bridge. Following migration or sinking of the
binucleate perikaryon, numerous cytoplasmic vesicles appear in the distal
cytoplasm. These vesicles fuse progressively together and form a single large
cavity or lacuna. The walls of this cavity are becoming at this point the walls
of two delaminated layers: (1) the distal anucleated cytoplasmic layer is
transformed into the oncospheral tegument and (2) the proximal thin cytoplasmic
layer is transformed into the "hook region membrane". This delamination of the
initially compact layer of distal cytoplasm into two layers seems to be closely
associated with differentiation of oncospheral hooks, the elongating blades of
which protrude progressively into a newly formed cavity. The pressure of hook
blades on the hook region membrane appears to facilitate its further separation
from the basal layer of distal cytoplasm which is transformed into the peripheral
layer of oncospheral tegument. In the mature oncosphere, the surface of this
peripheral layer forms a regular brush border of cytoplasmic processes or
microvilli and represents the true body covering of the hexacanth. The very thin
cytoplasmic connection between the peripheral layer of tegument and binucleate
perikaryon appears only very seldom in the ultrathin sections as a narrow
cytoplasmic strand and has a plasma membrane that is reinforced by a single row
of cortical microtubules. The HRM covers only one pole of the oncosphere and is
attached to the oncosphere surface. The HRM is clearly visible in the mature
oncosphere and is draped over the hook blades, the sharp points of which are
protected by moderately electron-dense caps. Comparison of the above morphology
with that of TEM study of the tegument of adult cestodes shows a great similarity
as well as homology in the body covering of both larval and adult cestodes.
PMID- 29335791
TI - Behavior of C-reactive protein in association with surgery of facial fracture and
the influence of dexamethasone.
AB - PURPOSE: To clarify pre- and postoperative C-reactive protein (CRP) levels in
patients with facial fractures and to investigate the influence of
perioperatively administered dexamethasone on postoperative CRP levels. PATIENTS
AND METHODS: Facial fracture patients were randomized to receive perioperatively
a total dose of 30 mg of dexamethasone (Oradexon(r)), whereas patients in the
control group received no glucocorticoid. The analysis included patients who had
CRP measured pre- and postoperatively. RESULTS: A total of 73 adult patients with
facial fractures were included in the final analysis. Mean CRP level was elevated
preoperatively and the level increased further after surgery. However,
postoperative CRP rise was significantly impeded by dexamethasone (p < 0.001),
regardless of gender, age, treatment delay, site of fracture, surgical approach,
and duration of surgery. CRP rise halved on the 1st postoperative day when
dexamethasone was used. In addition, dexamethasone resulted in a CRP decrease on
the 2nd postoperative day, whereas the CRP rise continued in the control group.
CONCLUSIONS: CRP rise is a normal body response after facial fracture and surgery
that can be markedly reduced with dexamethasone. CRP changes should be considered
with caution if perioperative dexamethasone is used.
PMID- 29335792
TI - Toward Exploring the Structure of Monolayer to Few-layer TaS2 by Efficient
Ultrasound-free Exfoliation.
AB - Tantalum disulfide nanosheets have attracted great interest due to its electronic
properties and device applications. Traditional solution-ased ultrasonic process
is limited by ultrasound which may cause the disintegration into submicron-sized
flake. Here, an efficient multi-step intercalation and ultrasound-free process
has been successfully used to exfoliate 1T-TaS2. The obtained TaS2 nanosheets
reveal an average thickness of 3 nm and several micrometers in size. The
formation of few-layer TaS2 nanosheets as well as monolayer TaS2 sheets is
further confirmed by atomic force microscopy images. The few-layer TaS2
nanosheets remain the 1T structure, whereas monolayer TaS2 sheets show lattice
distortion and may adopt the 1H-like structure with trigonal prism coordination.
PMID- 29335793
TI - Accuracy of emergency department triage using the Emergency Severity Index and
independent predictors of under-triage and over-triage in Brazil: a retrospective
cohort analysis.
AB - BACKGROUND: Emergency department (ED) triage is performed to prioritize care for
patients with critical and time-sensitive illness. Triage errors create
opportunity for increased morbidity and mortality. Here, we sought to measure the
frequency of under- and over-triage of patients by nurses using the Emergency
Severity Index (ESI) in Brazil and to identify factors independently associated
with each. METHODS: This was a single-center retrospective cohort study. The
accuracy of initial ESI score assignment was determined by comparison with a
score entered at the close of each ED encounter by treating physicians with full
knowledge of actual resource utilization, disposition, and acute outcomes. Chi
square analysis was used to validate this surrogate gold standard, via comparison
of associations with disposition and clinical outcomes. Independent predictors of
under- and over-triage were identified by multivariate logistic regression.
RESULTS: Initial ESI-determined triage score was classified as inaccurate for
16,426 of 96,071 patient encounters. Under-triage was associated with a
significantly higher rate of admission and critical outcome, while over-triage
was associated with a lower rate of both. A number of factors identifiable at
time of presentation including advanced age, bradycardia, tachycardia, hypoxia,
hyperthermia, and several specific chief complaints (i.e., neurologic complaints,
chest pain, shortness of breath) were identified as independent predictors of
under-triage, while other chief complaints (i.e., hypertension and allergic
complaints) were independent predictors of over-triage. CONCLUSIONS: Despite
rigorous and ongoing training of ESI users, a large number of patients in this
cohort were under- or over-triaged. Advanced age, vital sign derangements, and
specific chief complaints-all subject to limited guidance by the ESI algorithm
were particularly under-appreciated.
PMID- 29335795
TI - Combined effects of predator cues and competition define habitat choice and food
consumption of amphipod mesograzers.
AB - Predation has direct impact on prey populations by reducing prey abundance. In
addition, predator presence alone can also have non-consumptive effects on prey
species, potentially influencing their interspecific interactions and thus the
structure of entire assemblages. The performance of potential prey species may,
therefore, depend on both the presence of predators and competitors. We studied
habitat use and food consumption of a marine mesograzer, the amphipod
Echinogammarus marinus, in the presence/absence of a fish mesopredator and/or an
amphipod competitor. The presence of the predator affected both habitat choice
and food consumption of the grazer, indicating a trade-off between the use of
predator-free space and food acquisition. Without the predator, E. marinus were
distributed equally over different microhabitats, whereas in the presence of the
predator, most individuals chose a sheltered microhabitat and reduced their food
consumption. Furthermore, habitat choice of the amphipods changed in the presence
of interspecific competitors, also resulting in reduced feeding rates. The
performance of E. marinus is apparently driven by trait-mediated direct and
indirect effects caused by the interplay of predator avoidance and competition.
This highlights the importance of potential non-consumptive impacts of predators
on their prey organisms. The flexible responses of small invertebrate consumers
to the combined effects of predation and competition potentially lead to changes
in the structure of coastal ecosystems and the multiple species interactions
therein.
PMID- 29335794
TI - Effect of a calcitonin gene-related peptide-binding L-RNA aptamer on neuronal
activity in the rat spinal trigeminal nucleus.
AB - BACKGROUND: Calcitonin gene-related peptide (CGRP) plays a major role in the
pathogenesis of migraine and other primary headaches. Spinal trigeminal neurons
integrate nociceptive afferent input from trigeminal tissues including
intracranial afferents, and their activity is thought to reflect facial pain and
headache in man. CGRP receptor inhibitors and anti-CGRP antibodies have been
demonstrated to be therapeutically effective in migraine. In parallel, CGRP
receptor inhibition has been shown to lower spinal trigeminal neuron activity in
animal models of meningeal nociception. METHODS: In a rat model of meningeal
nociception, single cell activity of neurons in the spinal trigeminal nucleus
with meningeal afferent input was recorded to test a further pharmacological
approach, scavenging CGRP with a CGRP-binding L-RNA oligonucleotide, the L
aptamer NOX-C89. Cumulative ascending doses of NOX-C89 were intravenously
infused. RESULTS: Spontaneous activity of spinal trigeminal neurons did not
change after 0.05 mg/kg NOX-C89, however, after additional infusion of 0.5 mg/kg
and 5 mg/kg NOX-C89, spontaneous activity was dose-dependently reduced. Identical
doses of a control L-aptamer had no effect. This pharmacological effect of NOX
C89 was observed 10-25 min after infusion, but no difference was detected in the
period 0-5 min. For comparison, the previously investigated CGRP receptor
antagonist olcegepant had reduced activity within 5 min after infusion. Alongside
the reduced spontaneous activity, after infusion of NOX-C89 the heat-induced
neuronal activity was abolished. CONCLUSIONS: Scavenging CGRP by mirror-image RNA
aptamers provides further evidence that this approach can be used to control
spinal trigeminal activity.
PMID- 29335796
TI - Association between frailty and bone loss in patients undergoing maintenance
hemodialysis.
AB - Frailty is significantly associated with bone loss in the general population.
However, it is unclear whether this association also exists in patients
undergoing hemodialysis who have chronic kidney disease-mineral and bone disorder
(CKD-MBD). This study aimed to assess the association between frailty and bone
loss in patients undergoing hemodialysis. This cross-sectional study included 214
(90 women, 124 men) Japanese outpatients undergoing maintenance hemodialysis
three times per week, with a mean age of 67.1 years (women) and 66.8 years (men).
Frailty was defined based on criteria set forth by the Cardiovascular Health
Study (CHS)-19 (21.1%) women and 47 (37.9%) men were robust, 41 (45.6%) women and
43 (34.7%) men were pre-frail, and 30 (33.3%) women and 34 (27.4%) men were
frail. For bone mass, quantitative ultrasound (QUS) parameters (speed of sound,
broadband ultrasound attenuation, stiffness index) of the calcaneus were
measured. The association between frailty and QUS parameters was determined
separately for women and men using multivariate analysis of covariance (ANCOVA),
with adjustments for clinical characteristics including age, body mass index,
hemodialysis vintage, diabetes, current smoking, serum albumin, phosphate,
corrected calcium, intact parathyroid hormone, and medication for CKD-MBD
(vitamin D receptor activator, calcimimetics). ANCOVA revealed that all QUS
parameters declined significantly with increasing levels of frailty in both sexes
(P < 0.05). In conclusion, frailty (as defined by CHS criteria) should be
considered a risk factor for bone loss in patients undergoing hemodialysis.
PMID- 29335798
TI - 3D morphological change of skull base and fronto-temporal soft-tissue in the
patients with unicoronal craniosynostosis after fronto-orbital advancement.
AB - PURPOSE: This study aims to comprehensively evaluate the deformation of the skull
base and fronto-temporal soft tissue in the patients with anterior plagiocephaly
over 1 year of age by three-dimensional (3D) imaging after fronto-orbital
advancement (FOA). METHODS: We quantitatively analyzed the surgical results and
outcome of FOA performed in 10 patients with anterior plagiocephaly. The
measurements of the skull base and fronto-temporal soft tissue were performed
based on 3D computed tomography (CT) scan. We assessed symmetry of the skull base
and fronto-temporal soft tissue change. RESULTS: The mean age of patients at FOA
was 38.9 months. A significant asymmetry of the skull base was found in all the
patients. The growth of the anterior and middle fossae was restricted and the
deformation of the fronto-temporal region was marked by soft tissue measurements
in different grades. On the follow-up CT images 23.6 months after surgery, there
was prominent change (p < 0.05) between the two hemibases (CSO^ ratio) and
between the lengths and angles of the anterior and middle cranial hemi-fossae
(CX, CSX^, XSM^, XM ratio), especially in grade IIA. Anterior cranial vault
asymmetry index obviously decreased to - 1.2 from 12% after surgery (p < 0.05).
What's more, ACA^ was also proved to be less after surgical correction (19.91
degrees versus 8.29 degrees , p < 0.01) in grade IIA. The change of fronto
temporal soft tissue was significant such as the frontal angle, the angle of the
frontal plane, the fontal-temporal angle, and the angle of the temporal plane in
different grades. CONCLUSIONS: The asymmetry of the skull base and the
deformation of the fronto-temporal region can be presented by intracranial view
at over 1 year of age in different grades. FOA can correct the skeletal
malformation of the fronto-temporal region as well as soft tissue and the
asymmetry of the skull base was improved after surgical treatment.
PMID- 29335799
TI - Precisely Defined Polymers for Efficient Gene Delivery.
AB - Gene therapy requires successful delivery of therapeutic nucleic acids into
target cells; thus, efficient and safe gene delivery carriers are crucial to its
success. Although many polymeric materials have shown their potential as
effective nucleic acid carriers, the inherent heterogeneity and polydispersity of
these polymers hinder their application in clinical studies because of
difficulties in their further precise modification, structure-activity
relationship study, as well as consistent manufacturing. Therefore, precisely
defined polymers, with potential for site-specific optimization according to
structure-activity relationship information and highly controllable production,
have been extensively investigated. In this review, we focus on the design and
development of precisely defined polymers for efficient gene delivery,
illustrated with examples including dendrimers, peptide-based polymers, and
sequence-defined oligoaminoamide oligomers.
PMID- 29335797
TI - High-intensity aerobic interval training can lead to improvement in skeletal
muscle power among in-hospital patients with advanced heart failure.
AB - This study investigated the effectiveness and safety of interval training during
in-hospital treatment of patients with advanced heart failure. Twenty-four
consecutive patients with advanced symptomatic heart failure who were referred
for cardiac transplant evaluation were recruited. After performing aerobic
exercise for approximate intensity, high-intensity interval training (HIIT) was
performed. The protocol consisted of 3 or 4 sessions of 1-min high-intensity
exercise aimed at 80% of peak VO2 or 80% heart rate reserve, followed by 4-min
recovery periods of low intensity. In addition to the necessary laboratory data,
hand grip strength and knee extensor strength were evaluated at the start of
exercise training and both at the start and the end of HIIT. Knee extensor
strength was standardized by body weight. The BNP level at the start of exercise
training was 432 (812) pg/mL and it significantly decreased to 254 (400) pg/mL (p
< 0.001) at the end of HIIT. Hand grip strength did not change during course. By
contrast, knee extensor strength significantly increased during HIIT [4.42 +/-
1.43 -> 5.28 +/- 1.45 N/kg, p < 0.001], whereas the improvement of knee extensor
strength was not significant from the start of exercise training to the start of
HIIT. In addition, the change in knee extensor strength during HIIT was
significantly associated with the hemoglobin A1c level at the start of exercise
(R = - 0.55; p = 0.015). HIIT has a positive impact on skeletal muscle strength
among in-hospital patients with advanced heart failure.
PMID- 29335800
TI - Enrichment and characterization of a bacterial mixture capable of utilizing C
mannosyl tryptophan as a carbon source.
AB - C-Mannosylation, a protein-modification found in various eukaryotes, involves the
attachment of a single mannose molecule to selected tryptophan residues of
proteins. Since C-mannosyl tryptophan (CMW) was detected in human urine, it is
generally thought that CMW is not catabolized inside our body and instead is
excreted via the urine. This paper reports enrichment of a bacterial consortium
from soil that degrades CMW. The bacteria grew in minimal medium supplemented
with CMW as the carbon source. Interestingly, even after successive clonal picks
of individual colonies, several species were still present in each colony as
revealed by 16S rRNA gene sequence analysis, indicating that a single species may
not be responsible for this activity. A next generation sequencing (NGS) analysis
was therefore carried out in order to determine which bacteria were responsible
for the catabolism of CMW. It was found that a species of Sphingomonadaceae
family, but not others, increased with simultaneous decrease of CMW in the media,
suggesting that this species is most likely the one that is actively involved in
the degradation of CMW.
PMID- 29335801
TI - IgM Augments Complement Bactericidal Activity with Serum from a Patient with a
Novel CD79a Mutation.
AB - Antibody replacement therapy for patients with antibody deficiencies contains
only IgG. As a result, concurrent IgM and IgA deficiency present in a large
proportion of antibody deficient patients persists. Especially patients with IgM
deficiency remain at risk for recurrent infections of the gastrointestinal and
respiratory tract. The lack of IgM in the current IgG replacement therapy is
likely to contribute to the persistence of these mucosal infections because this
antibody class is especially important for complement activation on the mucosal
surface. We evaluated whether supplementation with IgM increased serum
bactericidal capacity in vitro. Serum was collected from a patient with
agammaglobulinemia and supplemented with purified serum IgM to normal levels.
Antibody and complement deposition on the bacterial surface was determined by
multi-color flow cytometry. Bacterial survival in serum was determined by colony
forming unit counts. We present a patient previously diagnosed with
agammaglobulinemia due to CD79A (Igalpha) deficiency revealing a novel pathogenic
insertion variant in the CD79a gene (NM_001783.3:c.353_354insT). Despite IgG
replacement therapy and antibiotic prophylaxis, this patient developed a
Campylobacter jejuni spondylodiscitis of lumbar vertebrae L4-L5. We found that
serum IgM significantly contributes to complement activation on the bacterial
surface of C. jejuni. Furthermore, supplementation of serum IgM augmented serum
bactericidal activity significantly. In conclusion, supplementation of
intravenous IgG replacement therapy with IgM may potentially offer greater
protection against bacterial infections, also in the context of increasing
antibiotic resistance.
PMID- 29335802
TI - The clinical relevance of drug-drug interaction between co-trimoxazole and
sacubitril/valsartan treatment in a heart failure patient: a case report and
overview of mechanisms and management in clinical practice.
PMID- 29335803
TI - Contribution of transposable elements and distal enhancers to evolution of human
specific features of interphase chromatin architecture in embryonic stem cells.
AB - Transposable elements have made major evolutionary impacts on creation of primate
specific and human-specific genomic regulatory loci and species-specific genomic
regulatory networks (GRNs). Molecular and genetic definitions of human-specific
changes to GRNs contributing to development of unique to human phenotypes remain
a highly significant challenge. Genome-wide proximity placement analysis of
diverse families of human-specific genomic regulatory loci (HSGRL) identified
topologically associating domains (TADs) that are significantly enriched for
HSGRL and designated rapidly evolving in human TADs. Here, the analysis of HSGRL,
hESC-enriched enhancers, super-enhancers (SEs), and specific sub-TAD structures
termed super-enhancer domains (SEDs) has been performed. In the hESC genome, 331
of 504 (66%) of SED-harboring TADs contain HSGRL and 68% of SEDs co-localize with
HSGRL, suggesting that emergence of HSGRL may have rewired SED-associated GRNs
within specific TADs by inserting novel and/or erasing existing non-coding
regulatory sequences. Consequently, markedly distinct features of the principal
regulatory structures of interphase chromatin evolved in the hESC genome compared
to mouse: the SED quantity is 3-fold higher and the median SED size is
significantly larger. Concomitantly, the overall TAD quantity is increased by 42%
while the median TAD size is significantly decreased (p = 9.11E-37) in the hESC
genome. Present analyses illustrate a putative global role for transposable
elements and HSGRL in shaping the human-specific features of the interphase
chromatin organization and functions, which are facilitated by accelerated
creation of novel transcription factor binding sites and new enhancers driven by
targeted placement of HSGRL at defined genomic coordinates. A trend toward the
convergence of TAD and SED architectures of interphase chromatin in the hESC
genome may reflect changes of 3D-folding patterns of linear chromatin fibers
designed to enhance both regulatory complexity and functional precision of GRNs
by creating predominantly a single gene (or a set of functionally linked genes)
per regulatory domain structures. Collectively, present analyses reveal critical
evolutionary contributions of transposable elements and distal enhancers to
creation of thousands primate- and human-specific elements of a chromatin folding
code, which defines the 3D context of interphase chromatin both restricting and
facilitating biological functions of GRNs.
PMID- 29335804
TI - Identification of a functional toxin-antitoxin system located in the genomic
island PYG1 of piezophilic hyperthermophilic archaeon Pyrococcus yayanosii.
AB - Toxin-antitoxin (TA) system is bacterial or archaeal genetic module consisting of
toxin and antitoxin gene that be organized as a bicistronic operon. TA system
could elicit programmed cell death, which is supposed to play important roles for
the survival of prokaryotic population under various physiological stress
conditions. The phage abortive infection system (AbiE family) belongs to
bacterial type IV TA system. However, no archaeal AbiE family TA system has been
reported so far. In this study, a putative AbiE TA system (PygAT), which is
located in a genomic island PYG1 in the chromosome of Pyrococcus yayanosii CH1,
was identified and characterized. In Escherichia coli, overexpression of the
toxin gene pygT inhibited its growth while the toxic effect can be suppressed by
introducing the antitoxin gene pygA in the same cell. PygAT also enhances the
stability of shuttle plasmids with archaeal plasmid replication protein Rep75 in
E. coli. In P. yayanosii, disruption of antitoxin gene pygA cause a significantly
growth delayed under high hydrostatic pressure (HHP). The antitoxin protein PygA
can specifically bind to the PygAT promoter region and regulate the transcription
of pygT gene in vivo. These results show that PygAT is a functional TA system in
P. yayanosii, and also may play a role in the adaptation to HHP environment.
PMID- 29335805
TI - Effects of nicotine on the biosynthesis of carotenoids in halophilic Archaea
(class Halobacteria): an HPLC and Raman spectroscopy study.
AB - Nicotine has a profound influence on the carotenoid metabolism in halophilic
Archaea of the class Halobacteria. In a study of Halobacterium salinarum,
Haloarcula marismortui and Halorubrum sodomense, using different analytical
techniques to monitor the production of different carotenoids as a function of
the presence of nicotine, we showed that the formation of alpha-bacterioruberin
was inhibited in all. In Hbt. salinarum, addition of nicotine led to a
significant change in the color of the culture due to the accumulation of
lycopene, in addition to the formation of bisanhydrobacterioruberin which does
not differ in color from alpha-bacterioruberin. Very little or no lycopene was
formed in Har. marismortui and in Hrr. sodomense; instead
bisanhydrobacterioruberin was the only major carotenoid found in nicotine-amended
cultures. The findings are discussed in the framework of the recently elucidated
biochemical pathway for the formation of the different carotenoid pigments
encountered in the Halobacteria.
PMID- 29335806
TI - Assessment of ocular toxoplasmosis patients reported at a tertiary center in the
northeast of Iran.
AB - PURPOSE: Ocular toxoplasmosis, which is caused by the single-cell parasite
Toxoplasma gondii, is currently the most significant cause of posterior uveitis
in the world. No previous studies have described the prevalence and clinical
features of ocular toxoplasmosis in the northeast of Iran. The purpose of the
current study was to address this gap. METHODS: In this retrospective study, the
medical records of 488 uveitis patients who presented to the Khatam-al-Anbia Eye
Hospital of Mashhad University of Medical Sciences, a tertiary ophthalmology
center in the northeast of Iran, between January 2013 and December 2015 were
evaluated. The clinical features and risk factors of 99 (20%) consecutive
patients with ocular toxoplasmosis were extracted. RESULTS: Ninety-nine including
53 (53.5%) female and 46 (46.5%) male patients with ocular toxoplasmosis were
included in the analysis. Reduced vision (77%) and floaters (15.2%) were the most
common presenting symptoms. The age category that was most affected by ocular
toxoplasmosis was 20-40 years (range: 11-65 years) with a mean age of 27.2. All
patients had retinochoroiditis, but just two had anterior uveitis. All of the
extracted patients, with the exception of three patients, had unilateral
involvement. None of the patients had any other medical disorders with the
exception of one woman, who had diabetes. Only four recurring ocular
toxoplasmosis patients were referred to the education hospital during the study.
Serology data were available for just 32 patients, of which 31 (96.8%) were IgG
positive, and 1 (3.2%) was IgM positive. CONCLUSION: Toxoplasma gondii was
responsible for 20% of the patients of uveitis that presented to the largest
ophthalmology center in the northeast of Iran. There is a high incidence of
patients of ocular toxoplasmosis in the northeast of Iran, and it is a
significant cause of uveitis and visual impairment in this area.
PMID- 29335807
TI - Assessment of in vitro cytotoxic and genotoxic activities of some trimethoprim
conjugates.
AB - Trimethoprim, a commonly used antibacterial agent, is widely applied in the
treatment of variety of infections in human. A few studies have demonstrated an
extensive exposure of man to antibiotics, but there is still a lack of data for
cytotoxic effects including nephrotoxicity, gastrointestinal toxicity,
hematotoxicity, neurotoxicity and ototoxicity. The main purpose behind this study
was to determine cytotoxic and genotoxic activities of trimethoprim (1),
trimethoprim with maleic acid (2) and trimethoprim in conjugation with oxalic
acid dihydrate (3). The cytotoxic effects of these three conjugates were
elucidated by employing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoium
bromide (MTT) assay using embryonic rat fibroblast-like cell line (F2408) and H
ras oncogene activated embryonic rat fibroblast-like cancer cell line (5RP7).
Additionally, determination of genotoxic activity of these three compounds were
studied by using cytokinesis blocked micronucleus assay (CBMN) in human
lymphocytes. The results demonstrated that trimethoprim alone and its combination
with other compounds are able to induce both cytotoxic and genotoxic damage on
cultured cells (F2408, 5RP7, human lymphocytes).
PMID- 29335808
TI - Perfluorooctanoic acid impaired glucose homeostasis through affecting adipose AKT
pathway.
AB - Perfluorooctanoic acid (PFOA) is commonly applied in manufactured products, and
its potential health risk is concerned greatly. Increasing evidences have
indicated PFOA-induced liver dysfunction. However, detailed molecular mechanism
has not been completely identified. In this study, we aimed to investigate the
mechanical association between PFOA exposure and AKT pathway in white adipose
tissue. As results, PFOA-treated mice showed increased blood glucose and insulin
levels, and induced insulin resistance. In addition, serum levels of leptin and
adiponectin in PFOA-treated mice were elevated. As shown in histological
examination, increased cell death counts in PFOA-treated adipose were observed,
as well as ultrastructural impairment in adipose cells was found. Further,
immunohistochemical stains exhibited GLUT4, p-AKT positive cells were down
regulated in PFOA-treated adipose, while PTEN immune-labeled cells were reduced.
In validated data, RT-PCR assay suggested adipose AKT mRNA was down-regulated in
PFOA-treated mice, and PTEN mRNA was increased. Western blot data showed that
intracellular PTEN protein level in PFOA-treated adipose was up-regulated, while
phosphorylation of AKT, GSK3beta levels were lowered dose-dependently. Taken
together, the present findings indicate that PFOA impaired glucose homeostasis
via negatively regulating AKT pathway in white adipose tissue.
PMID- 29335809
TI - Healthcare and Social Services Providers Who Serve Sexual and Gender Minorities
in a U.S.-Mexico Border City.
AB - Sexual and gender minorities, including lesbian, gay, bisexual, transgender, and
queer (LGBTQ) individuals, experience barriers to healthcare as a result of
stigma, discrimination, and poor cultural competence by healthcare and social
services providers (HCSSP). The purpose of the study is to increase access to
care and services for the LGBTQ community in a U.S.-Mexico border city by
identifying LGBTQ-friendly HCSSP. A survey, developed based on concerns voiced in
a predominantly Hispanic LGBTQ community, was administered to HCSSP and used to
create a referral list, "The Purple Pages of El Paso" (PPoEP). Overall, 77 HCSSP
have responded and 43 are included in the most recent version of the PPoEP. This
model for developing a referral list of providers can be adapted in areas where
LGBTQ communities face similar barriers to care and services. To be effective in
reducing barriers to care, PPoEP must be updatable and sustainable.
PMID- 29335810
TI - Sexual and Reproductive Health Education Needs, Gender Roles Attitudes and
Acceptance of Couple Violence According to Engaged Men and Women.
AB - This descriptive study was aimed to evaluate the attitudes of the engaged men and
women who are of legal age to marry towards gender roles and acceptance of couple
violence, and determine their sexual/reproductive health education needs. It was
conducted in two marriage registry offices in Ankara, Turkey. The study sample
consisted of 740 participants. Data were collected by using semi-structured form,
Gender Roles Attitude Scale and Acceptance of Couple Violence Scale. It was found
that the engaged couples had educational needs concerning sexual/reproductive
health; socio-demographic characteristics such as gender, age, education,
residence, and income level created significant differences in the attitudes
related to accepting gender roles and violence; and having an egalitarian
attitude towards gender roles decreased the rate of accepting violence between
the couples. Results indicate that premarital counseling is a promising strategy
to support engaged couples' sexual/reproductive health needs, and increase their
awareness about gender based couple violence in communities.
PMID- 29335811
TI - Surgical stress response and promotion of metastasis in colorectal cancer: a
complex and heterogeneous process.
AB - Surgery remains the curative treatment modality for colorectal cancer in all
stages, including stage IV with resectable liver metastasis. There is emerging
evidence that the stress response caused by surgery as well as other
perioperative therapies such as anesthesia and analgesia may promote growth of
pre-existing micro-metastasis or potentially initiate tumor dissemination.
Therapeutically targeting the perioperative period may therefore reduce the
effect that surgical treatments have in promoting metastases, for example by
combining beta-adrenergic receptor antagonists and cyclooxygenase-2 (COX-2)
inhibitors in the perioperative setting. In this paper, we highlight some of the
mechanisms that may underlie surgery-related metastatic development in colorectal
cancer. These include direct tumor spillage at the time of surgery, suppression
of the anti-tumor immune response, direct stimulatory effects on tumor cells, and
activation of the coagulation system. We summarize in more detail results that
support a role for catecholamines as major drivers of the pro-metastatic effect
induced by the surgical stress response, predominantly through activation of beta
adrenergic signaling. Additionally, we argue that an improved understanding of
surgical stress-induced dissemination, and more specifically whether it impacts
on the level and nature of heterogeneity within residual tumor cells, would
contribute to the successful clinical targeting of this process. Finally, we
provide a proof-of-concept demonstration that ex-vivo analyses of colorectal
cancer patient-derived samples using RGB-labeling technology can provide
important insights into the heterogeneous sensitivity of tumor cells to stress
signals. This suggests that intra-tumor heterogeneity is likely to influence the
efficacy of perioperative beta-adrenergic receptor and COX-2 inhibition, and that
ex-vivo characterization of heterogeneous stress response in tumor samples can
synergize with other models to optimize perioperative treatments and further
improve outcome in colorectal and other solid cancers.
PMID- 29335812
TI - Sperm telomere length in donor samples is not related to ICSI outcome.
AB - PURPOSE: Variations in sperm telomere length (STL) have been associated with
altered sperm parameters, poor embryo quality, and lower pregnancy rates, but for
normozoospermic men, STL relevance in IVF/ICSI is still uncertain. Moreover, in
all studies reported so far, each man's STL was linked to the corresponding
female partner characteristics. Here, we study STL in sperm donor samples, each
used for up to 12 women, in order to isolate and determine the relationship
between STL and reproductive outcomes. METHODS: Relative STL was determined by
qPCR in 60 samples used in a total of 676 ICSI cycles. Univariable and
multivariable statistical analyses were used to study the STL effect on
fertilization rate; embryo morphology; biochemical, clinical, and ongoing
pregnancy rates; and live birth (LB) rates. RESULTS: The average STL value was
4.5 (relative units; SD 1.9; range 2.4-14.2). Locally weighted scatterplot
smoothing regression and the rho-Spearman test did not reveal significant
correlations between STL and the outcomes analyzed. STL was not different between
cycles resulting or not in pregnancy and LB (Mann-Whitney U test, p > 0.05). No
significant effect of STL on reproductive outcomes was found, with the OR for
each unit increase in STL (95% CI) of 0.94 (0.86-1-04), 0.99 (0.9-1.09), 0.98
(0.89-1.09), and 0.93 (0.8-1.06) for biochemical, clinical, and ongoing pregnancy
and LB, respectively. The multilevel analysis confirmed that the effect of STL on
fertilization; biochemical, clinical, and ongoing pregnancy; and LB was not
significant (p > 0.05). CONCLUSION: After addressing STL independently from
female variables, results show that STL measurement is not useful to predict
reproductive outcomes in ICSI cycles using donor semen.
PMID- 29335814
TI - ?
PMID- 29335817
TI - Repurposing existing drugs for new AMPK activators as a strategy to extend
lifespan: a computer-aided drug discovery study.
AB - Dietary restriction is one of the several ways which could putatively extend
organisms' lifespan, ranging from Saccharomyces cerevisiae to rodents, by
activating the AMP-activated protein kinase (AMPK), an ATP/AMP sensor. Extensive
researches have shown that aging reduces sensibility of AMPK and eventually
causes energy imbalance in cells. Research in mammals' AMPK depicts that this
signaling molecule could control autophagy, improve cellular stress resistance
and suppress inflammatory responses. Hence, in this study we performed a drug
repurposing of 1908 FDA-approved drugs in order to discover putative safe
activators of AMPK and to find new applications for existing drugs. For this
purpose, FDA-approved drugs were screened by virtual screening and the ligand
protein interactions were carefully inspected. Moreover, through MM/PBSA
analysis, the binding affinity of hit compounds in gamma and alphabeta binding
sites were investigated. As Cangrelor, Nacitentan, Levoleucovorin and Glisoxepide
had lower binding affinities; we predicted that they would probably prove to be
more potential activators than C2. However, hit-compounds in alphabeta binding
site, exhibited higher unfavorable binding affinity. Hence, present findings can
prove to be valuable for discovering new activators for AMPK.
PMID- 29335813
TI - Organic acidurias in adults: late complications and management.
AB - Organic acidurias (synonym, organic acid disorders, OADs) are a heterogenous
group of inherited metabolic diseases delineated with the implementation of gas
chromatography/mass spectrometry in metabolic laboratories starting in the 1960s
and 1970s. Biochemically, OADs are characterized by accumulation of mono-, di-
and/or tricarboxylic acids ("organic acids") and corresponding coenzyme A,
carnitine and/or glycine esters, some of which are considered toxic at high
concentrations. Clinically, disease onset is variable, however, affected
individuals may already present during the newborn period with life-threatening
acute metabolic crises and acute multi-organ failure. Tandem mass spectrometry
based newborn screening programmes, in particular for isovaleric aciduria and
glutaric aciduria type 1, have significantly reduced diagnostic delay. Dietary
treatment with low protein intake or reduced intake of the precursor amino
acid(s), carnitine supplementation, cofactor treatment (in responsive patients)
and nonadsorbable antibiotics is commonly used for maintenance treatment.
Emergency treatment options with high carbohydrate/glucose intake,
pharmacological and extracorporeal detoxification of accumulating toxic
metabolites for intensified therapy during threatening episodes exist. Diagnostic
and therapeutic measures have improved survival and overall outcome in
individuals with OADs. However, it has become increasingly evident that the
manifestation of late disease complications cannot be reliably predicted and
prevented. Conventional metabolic treatment often fails to prevent irreversible
organ dysfunction with increasing age, even if patients are considered to be
"metabolically stable". This has challenged our understanding of OADs and has
elicited the discussion on optimized therapy, including (early) organ
transplantation, and long-term care.
PMID- 29335816
TI - Organ reserve, excess metabolic capacity, and aging.
AB - "Organ reserve" refers to the ability of an organ to successfully return to its
original physiological state following repeated episodes of stress. Clinical
evidence shows that organ reserve correlates with the ability of older adults to
cope with an added workload or stress, suggesting a role in the process of aging.
Although organ reserve is well documented clinically, it is not clearly defined
at the molecular level. Interestingly, several metabolic pathways exhibit excess
metabolic capacities (e.g., bioenergetics pathway, antioxidants system,
plasticity). These pathways comprise molecular components that have an excess of
quantity and/or activity than that required for basic physiological demand in
vivo (e.g., mitochondrial complex IV or glycolytic enzymes). We propose that the
excess in mtDNA copy number and tandem DNA repeats of telomeres are additional
examples of intrinsically embedded structural components that could comprise
excess capacity. These excess capacities may grant intermediary metabolism the
ability to instantly cope with, or manage, added workload or stress. Therefore,
excess metabolic capacities could be viewed as an innate mechanism of
adaptability that substantiates organ reserve and contributes to the cellular
defense systems. If metabolic excess capacities or organ reserves are impaired or
exhausted, the ability of the cell to cope with stress is reduced. Under these
circumstances cell senescence, transformation, or death occurs. In this review,
we discuss excess metabolic and structural capacities as integrated metabolic
pathways in relation to organ reserve and cellular aging.
PMID- 29335818
TI - Dorsal shaving affects concentrations of faecal cortisol metabolites in lactating
golden hamsters.
AB - Breeding of golden hamsters is classically performed at thermal conditions
ranging from 20 to 24 degrees C. However, growing evidence suggests that
lactating females suffer from heat stress. We hypothesised that shaving females
dorsally to maximise heat dissipation may reduce stress during reproduction. We
thus compared faecal cortisol metabolites (FCM) from shaved golden hamster
mothers with those from unshaved controls. We observed significantly lower FCM
levels in the shaved mothers (F1,22 = 8.69, p = 0.0075) pointing to lower stress
due to ameliorated heat dissipation over the body surface. In addition, we
observed 0.4 degrees C lower mean subcutaneous body temperatures in the shaved
females, although this effect did not reach significance (F1,22 = 1.86, p =
0.18). Our results suggest that golden hamsters having body masses being more
than four times that of laboratory mice provide a very interesting model to study
aspects of lactation and heat production at the same time.
PMID- 29335819
TI - NMDA Receptor GluN2 Subtypes Control Epileptiform Events in the Hippocampus.
AB - NMDA receptors (NMDARs) play a key role in synaptic plasticity and
excitotoxicity. Subtype-specific role of NMDAR in neural disorders is an emerging
area. Recent studies have revealed that mutations in NMDARs are a cause for
epilepsy. Hippocampus is a known focal point for epilepsy. In hippocampus,
expression of the NMDAR subtypes GluN1/GluN2A and GluN1/GluN2B is temporally
regulated. However, the pharmacological significance of these subtypes is not
well understood in epileptic context/models. To investigate this, epilepsy was
induced in hippocampal slices by the application of artificial cerebrospinal
fluid that contained high potassium but no magnesium. Epileptiform events (EFEs)
were recorded from the CA1 and DG areas of hippocampus with or without subtype
specific antagonists. Irrespective of the age group, CA1 and DG showed
epileptiform activity. The NMDAR antagonist AP5 was found to reduce the number of
EFEs significantly. However, the application of subtype-specific antagonists (TCN
201 for GluN1/GluN2A and Ro 25-69811 for GluN1/GluN2B) revealed that EFEs had
area-specific and temporal components. In slices from neonates, EFEs in CA1 were
effectively reduced by Ro 25-69811, but were largely insensitive to TCN 201. In
contrast, EFEs in DG were equally sensitive to both of the subtype-specific
antagonists. However, the differential sensitivity for the antagonists observed
in neonates was absent in later developmental stages. The study provides a
functional insight into the NMDAR subtype-dependent contribution of EFEs in
hippocampus of young rats, which may have implications in treating childhood
epilepsy and avoiding unnecessary side effects of broad spectrum antagonists.
PMID- 29335820
TI - How much do we know about hemolytic capability of pathogenic Candida species?
AB - Hemolytic factor production by pathogenic Candida species is considered an
important attribute in promoting survival within the mammal host through the
ability to assimilate iron from the hemoglobin-heme group. Hemolytic capability
has been evaluated for Candida species based on hemolysis zones on plate assay,
analysis of hemolytic activity in liquid culture medium, and hemolysis from cell
free culture broth. The production of hemolytic factor is variable among Candida
species, where C. parapsilosis is the less hemolytic species. In general, no
intraspecies differences in beta-hemolytic activities are found among isolates
belonging to C. albicans, C. glabrata, C. krusei, C. tropicalis, and C.
parapsilosis. The production of hemolytic factor by Candida species is affected
by several factors such as glucose supplementation in the culture medium, blood
source, presence of erythrocytes and hemoglobin, and presence of electrolytes. On
the basis of existing achievements, more researches are still needed in order to
extend our knowledge about the biochemical nature of hemolytic molecules produced
by distinct Candida species, the mechanism of hemolysis, and the molecular basis
of the hemolytic factor expression.
PMID- 29335821
TI - Maternal incarceration, child protection, and infant mortality: a descriptive
study of infant children of women prisoners in Western Australia.
AB - BACKGROUND: There are no population statistics collected on a routine basis on
the children of prisoners in Australia. Accordingly, their potential
vulnerability to adverse outcomes remains unclear. This study draws on linked
administrative data to describe the exposure of children aged less than 2 years
to maternal imprisonment in Western Australia, their contact with child
protection services, and infant mortality rates. RESULTS: In Western Australia,
36.5 per 1000 Indigenous (n = 804) and 1.3 per 1000 non-Indigenous (n = 395)
children born between 2001 and 2011 had mothers imprisoned after birth to age 2
years. One-third of infants' mothers had multiple imprisonments (maximum of 11).
Nearly half (46%) of prison stays were for <=2 weeks, 12% were between 2 and 4
weeks, 14% were for 1-3 months, and 28% were longer than three months.
Additionally, 17.4 per 1000 Indigenous (n = 383) and 0.5 per 1000 non-Indigenous
(n = 150) children had mothers imprisoned during pregnancy. Half of the children
with a history of maternal incarceration in pregnancy to age 2 years came into
contact with child protection services by their second birthday, with 31% of
Indigenous and 35% of non-Indigenous children entering out-of-home care. Rates of
placement in care were significantly higher for Indigenous children (Relative
Risk (RR) 27.30; 95%CI 19.19 to 38.84; p < .001) and for non-Indigenous children
(RR 110.10; 95%CI 61.70 to 196.49; p < .001) with a history of maternal
imprisonment compared to children of mothers with no corrections record. Infant
mortality for children whose mothers were imprisoned up to 5 years before birth
or within their first year after birth was higher than for children of mothers
with no corrections record for both Indigenous (RR 2.36; 95%CI 1.41 to 3.95; p =
.001) and non-Indigenous children (RR 2.28; 95%CI 0.75 to 6.97; p = .147).
CONCLUSIONS: This study highlights the particular vulnerability of children whose
mothers have been incarcerated and the importance of considering their needs
within corrective services policies and procedures. Prison may present an
opportunity to identify and work with vulnerable families to help improve
outcomes for children as well as mothers.
PMID- 29335822
TI - Emergency department throughput: an intervention.
AB - Shortening emergency department (ED) boarding time and managing hospital bed
capacity by expediting the inpatient discharge process have been challenging for
hospitals nationwide. The objective of this study is was to explore the effect of
an innovative prospective intervention on hospital workflow, specifically on
early inpatient discharges and the ED boarding time. The intervention consisted
of a structured nursing "admission discharge transfer" (ADT) protocol receiving
new admissions from the ED and helping out floor nursing with early discharges.
ADT intervention was implemented in a 38-bed hospitalist run inpatient unit at an
academic hospital. The study population consisted of 4486 patients (including
inpatient and observation admissions) who were hospitalized to the medicine unit
from March 2013-March 2014. Of these hospitalizations, 2259 patients received the
ADT intervention. Patients' demographics, discharge and ED boarding data were
collected for from March 4, 2013 to March 31, 2014 for both intervention and
control groups (28 weeks each). Chi-square and unpaired t tests were utilized to
compare population characteristics. Poisson regression analysis was conducted to
estimate the association between intervention and hospital length of stay
adjusted for differences in patient demographics. Mean age of the study
population was 58.6 years, 23% were African Americans and 55% were women. A
significant reduction in ED boarding time (p < 0.001) and improvement in early
(before 2 PM) hospital discharges (p = 0.01) were noticed among patients in the
intervention groups. There was a slight but significant reduction in hospital
length of stay for observation patients in the intervention group; however, no
such difference was noted for inpatient admissions. Our study showed that
dedicating nursing resources towards ED-boarded patients and early inpatient
discharges can significantly improve hospital workflow and reduce hospital length
of stay.
PMID- 29335823
TI - [Drugs for intravenous induction of anesthesia: propofol].
AB - In a series of articles dealing with hypnotics for induction of anesthesia, this
article describes the development and current value of propofol. Its significance
far exceeds that of a pure induction hypnotic (sedation in diagnostic and
therapeutic procedures and on the intensive care unit). Propofol is also used for
sedation in diagnostic and therapeutic procedures and on the intensive care unit.
In the field of induction of anesthesia, the alternatives are barely used. Some
contraindications are still controversial whereas others are no longer
sufficiently anchored in the users' awareness (widespread off-label use). Adverse
effects, such as injection pain, infection risk and propofol-related infusion
syndrome (PRIS) could be significantly reduced by pharmacovigilance. With
appropriate caution nearly the whole spectrum of anesthesiology patients can be
treated using propofol. The hemodynamic side effects and the rare but potentially
fatal PRIS are limitations. Further developments address the water solubility and
the solubilizing agents of propofol.
PMID- 29335824
TI - Broad-spectrum resistance of Pseudomonas aeruginosa from shellfish: infrequent
acquisition of novel resistance mechanisms.
AB - Pseudomonas aeruginosa is one the most common multidrug-resistant pathogens
worldwide. It has been previously detected in marine shellfish, but its
antibiotic resistance in such environment has not been explored. By combining PCR
detection of acquired genes, and resistance-nodulation-cell division (RND) efflux
studying, we investigated the multifactorial resistance traits of 108 P.
aeruginosa isolates recovered from wild-growing Mediterranean mussels (Mytilus
galloprovincialis) in Croatia. Eleven different resistance profiles were found,
with the main mechanism being the overexpression of intrinsic efflux pump(s),
particularly MexAB-OprM. Several acquired resistance determinants were detected,
including the beta-lactamase gene blaTEM-116, sulfamethoxazole resistance gene
sul1, and the class 1 integron gene cassette carrying the streptomycin resistance
gene aadA7. This study evidenced the multiple resistance in P. aeruginosa in
shellfish from human-impacted marine environment, pointing to the underestimated
role of the marine habitat for maintenance of multiresistant P. aeruginosa and,
consequently, the potential risk for human and environmental health.
PMID- 29335825
TI - Application of artificial intelligence using a convolutional neural network for
detecting gastric cancer in endoscopic images.
AB - BACKGROUND: Image recognition using artificial intelligence with deep learning
through convolutional neural networks (CNNs) has dramatically improved and been
increasingly applied to medical fields for diagnostic imaging. We developed a CNN
that can automatically detect gastric cancer in endoscopic images. METHODS: A CNN
based diagnostic system was constructed based on Single Shot MultiBox Detector
architecture and trained using 13,584 endoscopic images of gastric cancer. To
evaluate the diagnostic accuracy, an independent test set of 2296 stomach images
collected from 69 consecutive patients with 77 gastric cancer lesions was applied
to the constructed CNN. RESULTS: The CNN required 47 s to analyze 2296 test
images. The CNN correctly diagnosed 71 of 77 gastric cancer lesions with an
overall sensitivity of 92.2%, and 161 non-cancerous lesions were detected as
gastric cancer, resulting in a positive predictive value of 30.6%. Seventy of the
71 lesions (98.6%) with a diameter of 6 mm or more as well as all invasive
cancers were correctly detected. All missed lesions were superficially depressed
and differentiated-type intramucosal cancers that were difficult to distinguish
from gastritis even for experienced endoscopists. Nearly half of the false
positive lesions were gastritis with changes in color tone or an irregular
mucosal surface. CONCLUSION: The constructed CNN system for detecting gastric
cancer could process numerous stored endoscopic images in a very short time with
a clinically relevant diagnostic ability. It may be well applicable to daily
clinical practice to reduce the burden of endoscopists.
PMID- 29335827
TI - Satisfactory arterial repair 1 year after ultrathin strut biodegradable polymer
sirolimus-eluting stent implantation: an angioscopic observation.
AB - The ultrathin strut biodegradable polymer sirolimus-eluting stent (Orsiro, O-SES)
exhibits satisfactory clinical outcomes. However, no report to date has
documented the intravascular status of artery repair after O-SES implantation. We
examined 5 O-SES placed in 4 patients (age 65 +/- 12 years, male 75%) presenting
with stable angina pectoris due to de novo lesions in native coronary arteries.
Coronary angioscopy was performed immediately after percutaneous coronary
intervention and 1 year later. Angioscopic images were analyzed to determine the
following: (1) dominant grade of neointimal coverage (NIC) over the stent; (2)
maximum yellow plaque grade; and (3) existence of thrombus. Yellow plaque grade
was evaluated both immediately after stent implantation and at the time of follow
up observation. The other parameters were evaluated at the time of follow-up
examination. NIC was graded as: grade 0, stent struts exposed; grade 1, struts
bulging into the lumen, although covered; grade 2, struts embedded in the
neointima, but translucent; grade 3, struts fully embedded and invisible. Yellow
plaque severity was graded as: grade 0, white; grade 1, light yellow; grade 2,
yellow; and grade 3, intensive yellow. Angioscopic findings at 1 year
demonstrated the following: dominant NIC grade 1, grade 2, and grade 3 in 1, 2,
and 2 stents, respectively; all stents were covered to some extent; focal
thrombus adhesion was observed in only 1 stent. Yellow plaque grade did not
change from immediately after stent implantation to follow-up. O-SES demonstrated
satisfactory arterial repair 1 year after implantation.
PMID- 29335826
TI - High-salt- and cholesterol diet-associated cognitive impairment attenuated by
tannins-enriched fraction of Emblica officinalis via inhibiting NF-kB pathway.
AB - Metabolic disorders are closely associated with dietary habits and seem to be
related to neuroinflammation and neurodegenerative disease in humans. Emblica
officinalis (EOT) fruits not only have good nutritional value but also have
excellent therapeutic potential. We used a tannins-enriched fraction of EOT fruit
with the expectation of controlling diet-induced neuroinflammation and cognitive
impairment in rats. A high-salt and cholesterol diet (HSCD) was used to induce
neuroinflammation and cognitive impairment in rats. The diet of the rats was then
supplemented with EOT (100 and 200 mg/kg b.w.) for 7 weeks. In order to evaluate
the neuroprotective effects of EOT; in silico study, neurobehavioral tests,
biochemical analyses, and immunohistochemical studies were performed. In silico
study of p50 (NF-kappaB1) receptors with emblicanin (the main constituent of EOT)
suggests that EOT has binds to NF-kappaB. EOT treatment reversed the HSCD-induced
behavioral and memory disturbances in a step-down-type passive avoidance test.
EOT treatment also inhibited HSCD-induced NF-kappaB upstream signaling, including
the release of Th1, such as TNF-alpha, and downstream signaling Th2, such as IL
10, by flow cytometer. In addition, EOT treatment attentuated the HSCD-induced
increase in the level of cognitive impairment markers, such as amyloid beta.
Furthermore, immunohistochemical results demonstrated that EOT modulated neuronal
cell death by inhibiting the overexpression of NF-kB in brain. This study
confirms that EOT may be a promising therapy in ameliorating the neurotoxicity of
HSCD; however further studies are warranted to elucidate the exact mechanism of
action of EOT.
PMID- 29335828
TI - Low, but Not High, Doses of Copper Sulfate Impair Synaptic Plasticity in the
Hippocampal CA1 Region In Vivo.
AB - Previous studies have shown the inhibitory effect of the in vitro application of
copper sulfate on hippocampal long-term potentiation. While in vivo
administration of copper did not affect spatial learning and memory. To find
possible answers to this controversial issue, we evaluate the effect of different
doses of copper sulfate on in vivo long-term potentiation, synaptic transmission,
and paired-pulse behavior of CA1 pyramidal cells. Thirty-two male Wistar rats
were divided into four groups: control, 5, 10, and 15 mg of copper sulfate. Field
excitatory postsynaptic potential from the stratum radiatum of CA1 neurons was
recorded following Schaffer collateral stimulation in rats. Spike amplitude, long
term potentiation and paired-pulse index were measured in all groups. The results
of this study showed that 5 mg/kg copper sulfate increased synaptic transmission
and inhibited long-term potentiation and decreased the hippocampal paired-pulse
ratio, while 10 and 15 mg/kg copper sulfate did not affect CA1 synaptic
transmission properties. Low, but not high, doses of copper sulfate affect
synaptic plasticity. This finding may explain the difference between the effect
of copper on synaptic plasticity and spatial learning and memory.
PMID- 29335829
TI - Pancreaticoduodenectomy for periampullary tumours: a review article based on
Surveillance, End Results and Epidemiology (SEER) database.
AB - INTRODUCTION: This study set to examine relative survival of patients with
periampullary cancers undergoing pancreaticoduodenectomy (PD). METHODS: Using the
Surveillance, End Results and Epidemiology (SEER) database, this study identified
9877 patients with non-metastatic pancreatic adenocarcinoma who underwent PD
between 2004 and 2013. RESULTS: Ampullary carcinomas have the best survival among
periampullary malignancies. Lymph node ratio is a significant prognostic factor,
even when stratified by tumour types. Patients receiving adjuvant radiotherapy
following PD have superior survival than patients without radiotherapy (median 25
vs 20 months, p < 0.001), particularly ductal adenocarcinoma (HR: 0.74, CI95%
0.69-0.78; p < 0.001), cholangiocarcinoma (HR: 0.75, CI95% 0.59-0.97; p = 0.027),
and ampullary carcinoma (HR: 0.79, CI95% 0.64-0.98; p = 0.029) with greatest
survival benefit at 1-year postresection. CONCLUSION: Future studies aiming to
further define genetic signatures of individual periampullary cancers would allow
a personalised therapeutic approach in improving survival.
PMID- 29335830
TI - From imaging to biology of glioblastoma: new clinical oncology perspectives to
the problem of local recurrence.
AB - GBM is one of the most common and aggressive brain tumors. Surgery and adjuvant
chemoradiation have succeeded in providing a survival benefit. Although most
patients will eventually experience local recurrence, the means to fight
recurrence are limited and prognosis remains poor. In a disease where local
control remains the major challenge, few trials have addressed the efficacy of
local treatments, either surgery or radiation therapy. The present article
reviews recent advances in the biology, imaging and biomarker science of GBM as
well as the current treatment status of GBM, providing new perspectives to the
problem of local recurrence.
PMID- 29335832
TI - Lateral trochanteric pain following total hip arthroplasty: radiographic
assessment of altered biomechanics as a potential aetiology.
AB - INTRODUCTION: Lateral trochanteric pain (LTP) complicates up to 17% of cases of
total hip arthroplasty (THA). Studies have refuted underlying trochanteric
bursitis. Restoration of the femoral offset and reproduction of the natural
femoral centre of rotation are important in successful arthroplasty. LTP is
believed to be associated with their alteration. AIM: The aim of our study was to
evaluate the effect of femoral offset and centre of rotation on the incidence of
LTP post-THA. METHODS: A retrospective case control study was developed from 158
patients who underwent a THA over a two-year period to form two patient cohorts.
Twenty-nine patients diagnosed with LTP were matched with 110 control subjects.
The direct lateral approach was used in all cases. Anterior-posterior pelvic
radiographs before and after surgery were compared to assess the femoral, cup and
global offsets and limb length discrepancies between the two groups. Statistical
analyses were performed using the Mann-Whitney U test and independent samples t
test. RESULTS: Twenty-nine diagnosed with post-operative LTP. Sixty-two percent
of symptomatic patients were female (p = 0.13). The median ages were 74.33
(symptomatic) and 70.71 (control) (p = 0.11). The differences (pre-post) of the
femoral (p = 0.17), cup (p = 0.5) and global offsets (p = 0.99) and mean of limb
length discrepancy (LLD) (p = 0.83) were not significant between the two groups.
CONCLUSION: No relationship was found between LTP and femoral offset or femoral
centre of rotation. Disruption of the soft tissues during a lateral approach with
resultant abductor tear, tendon defects and tendinitis might play a role in LTP
and explain the apparent efficacy of corticosteroid injections.
PMID- 29335833
TI - Regulation of Bone Metabolism by microRNAs.
AB - PURPOSE OF REVIEW: The small non-coding microRNAs (miRNAs) have emerged as
important post-transcriptional regulators of various physiological and
pathological processes. The purpose of this article is to review the important
recent advances on the role of miRNAs in bone remodeling and metabolic bone
disorders. RECENT FINDINGS: In a physiological context, miRNAs regulate bone
formation and bone resorption, thereby contributing to the maintenance of bone
homeostasis. Under pathological conditions, an aberrant miRNA signaling
contributes to the onset and progression of skeletal disorders, such as
osteoporosis. Furthermore, miRNAs can be secreted to circulation and have
clinical potential as non-invasive biomarkers. In a therapeutic setting, miRNA
delivery or antagonism has been reported to affect several diseases under pre
clinical conditions thereby emerging as novel pharmacological tools. miRNAs are
key regulators of bone remodeling in health and disease. The future perspectives
in the field include the role of secreted miRNAs in cell-cell communication in
the bone environment. Furthermore, the clinical potential of using miRNAs as
diagnostic tools and therapeutic targets to treat metabolic bone diseases
provides an attractive future direction.
PMID- 29335831
TI - Quality of inter-hospital transportation in 431 transport survivor patients
suffering from acute respiratory distress syndrome referred to specialist
centers.
AB - BACKGROUND: The acute respiratory distress syndrome (ARDS) is a life-threatening
condition. In special situations, these critically ill patients must be
transferred to specialized centers for escalating treatment. The aim of this
study was to evaluate the quality of inter-hospital transport (IHT) of ARDS
patients. METHODS: We evaluated medical and organizational aspects of structural
and procedural quality relating to IHT of patients with ARDS in a prospective
nationwide ARDS study. The qualification of emergency staff, the organizational
aspects and the occurrence of critical events during transport were analyzed.
RESULTS: Out of 1234 ARDS patients, 431 (34.9%) were transported, and 52 of these
(12.1%) treated with extracorporeal membrane oxygenation. 63.1% of transferred
patients were male, median age was 54 years, and 26.8% of patients were obese.
All patients were mechanically ventilated during IHT. Pressure-controlled
ventilation was the preferred mode (92.1%). Median duration to organize the IHT
was 165 min. Median distance for IHT was 58 km, and median duration of IHT 60
min. Forty-two patient-related and 8 technology-related critical events (11.6%,
50 of 431 patients) were observed. When a critical event occurred, the PaO2/FiO2
ratio before transport was significant lower (68 vs. 80 mmHg, p = 0.017). 69.8%
of physicians and 86.7% of paramedics confirmed all transfer qualifications
according to requirements of the German faculty guidelines (DIVI). CONCLUSIONS:
The transport of critically ill patients is associated with potential risks. In
our study the rate of patient- and technology-related critical events was
relatively low. A severe ARDS with a PaO2/FiO2 ratio < 70 mmHg seems to be a risk
factor for the appearance of critical events during IHT. The majority of
transport staff was well qualified. Time span for organization of IHT was
relatively short. ECMO is an option to transport patients with a severe ARDS
safely to specialized centers. Trial registration NCT02637011
(ClinicalTrials.gov, Registered 15 December 2015, retrospectively registered).
PMID- 29335835
TI - Etiology of invasive candidosis agents in Russia: a multicenter epidemiological
survey.
AB - A multicenter prospective epidemiological survey on the etiologic agents of
invasive candidosis was conducted in Russia in the period of 2012-2014. Samples
were collected from 284 patients with invasive candidosis and Candida species
isolated by culture. The species were identified by DNA sequencing and MALDI-TOF
massspectrometry. A total of 322 isolates were recovered, in which 96% of Sandida
species belonged to six major species, namely, C. albicans (43.2%), C.
parapsilosis (20.2%), C. glabrata (11.5%), C. tropicalis (9.6%), C. krusei
(6.2%), and C. guilliermondii (5.3%). Most Candida species were isolated from
blood samples (83.23%). Notably, the prevalence rate of C. albicans reduced from
52.38% to 32.79% (2012 vs. 2014) (P = 0.01) whereas that of non-C. albicans
increased from 47.62% (2012) to 67.21% (2014) (P < 0.01). Species distribution
differed among geographical regions; specifically, the prevalence rate of C.
albicans as an etiologic agent of invasive candidosis in Siberian Federal region
was significantly higher than that in other Federal regions. Results indicated a
shift from C. albicans to non-C. albicans. Therefore, a detailed investigation on
the contributing factors and appropriate treatment of invasive candidosis is
needed.
PMID- 29335834
TI - Genetics of Osteopetrosis.
AB - PURPOSE OF REVIEW: The term osteopetrosis refers to a group of rare skeletal
diseases sharing the hallmark of a generalized increase in bone density owing to
a defect in bone resorption. Osteopetrosis is clinically and genetically
heterogeneous, and a precise molecular classification is relevant for prognosis
and treatment. Here, we review recent data on the pathogenesis of this disorder.
RECENT FINDINGS: Novel mutations in known genes as well as defects in new genes
have been recently reported, further expanding the spectrum of molecular defects
leading to osteopetrosis. Exploitation of next-generation sequencing tools is
ever spreading, facilitating differential diagnosis. Some complex phenotypes in
which osteopetrosis is accompanied by additional clinical features have received
a molecular classification, also involving new genes. Moreover, novel types of
mutations have been recognized, which for their nature or genomic location are at
high risk being neglected. Yet, the causative mutation is unknown in some
patients, indicating that the genetics of osteopetrosis still deserves intense
research efforts.
PMID- 29335836
TI - Adipogenesis and lipid production in adipocytes subjected to sustained tensile
deformations and elevated glucose concentration: a living cell-scale model system
of diabesity.
AB - Adipocyte fate commitment is characterized by morphological changes of
fibroblastic pre-adipocyte cells, and specifically by accumulation of lipid
droplets (LDs) as part of the adipogenesis metabolism. Formation of LDs indicates
the production of triglycerides from glucose through an insulin-regulated glucose
internalization process. In obesity, adipocytes typically become insulin
resistant, and glucose transport into the cells is impaired, resulting in type 2
diabetes. In the present study, we monitored the adipogenesis in 3T3-L1 cultured
cells exposed to high (450 mg/dL hyperglycemia) and low (100 mg/dL physiological)
glucose concentrations, in a novel cell culture model system of diabesity. In
addition to glucose conditions, cells were concurrently exposed to different
substrate tensile strains (12% and control) based on our prior work which
revealed that adipogenesis is accelerated in cultures subjected to static,
chronic substrate tensile deformations. Phase-contrast images were taken
throughout the adipogenesis process (3 weeks) and were analyzed by an image
processing algorithm which quantitatively monitors cell differentiation and lipid
accumulation (number of LDs per cell and their radius as well as cell size and
shape). The results indicated that high glucose concentrations and substrate
tensile strains delivered to adipocytes accelerated lipid production by 1.7- and
1.4-fold, respectively. In addition, significant changes in average cell
projected area and in other morphological attributes were observed during the
differentiation process. The importance of this study is in characterizing the
adipogenesis parameters as potential read-outs that can predict the occurrence of
insulin resistance in the development of diabesity.
PMID- 29335837
TI - Backbone chemical shift assignments of the glycine cleavage complex H protein of
Escherichia coli.
AB - Glycine cleavage complex H protein (GcvH) is one of the four components that form
the glycine cleavage complex (GCS), essential for the synthesis of C1 (one-carbon
units) for cell metabolism, by the oxidative cleavage of glycine. The activity of
this complex is induced in the presence of exogenous glycine, and is repressed by
purines. GCS, in cooperation with GCA (serine hydroxymethyltransferase) regulates
the endogenous levels of glycine and C1 units in the cell. GcvH, the lipoamide
containing component of the complex, plays an indispensable role in this
reaction, as its prosthetic group shuttles between the active site of the three
other components of the GCS complex sequentially. In environments rich in
exogenous lipoic acid, GcvH is converted to lipoyl-GcvH by Lipoate protein ligase
(LplA), by the salvage pathway. When exogenous lipoic acid is deficient, it is
post-translationally modified to lipoyl-GcvH by the consecutive action of two
enzymes, (a) Lipoate protein ligase B (LipB) and (b) Lipoyl synthase (LipA).
Although, the crystal structure has been determined for Escherichia coli GcvH, no
information exists for its interaction with LipB or LipA. Therefore, we plan to
study its interactions with the aforementioned enzymes. As a first step, we have
carried out the complete backbone chemical shift assignments of the E. coli
glycine cleavage complex H protein in its apo-form, as well as its C8-
intermediate.
PMID- 29335839
TI - Successful replacement of the longest worldwide in situ Nanostim leadless cardiac
pacemaker for a Micra Transcatheter Pacing System.
PMID- 29335838
TI - Effect of immunonutrition on colorectal cancer patients undergoing surgery: a
meta-analysis.
AB - PURPOSE: Immunonutrition has been used to prevent the complications after
colorectal elective surgery. This systematic review aimed to analyze and assess
the effect of immunonutrition on colorectal cancer patients who received elective
surgery. METHODS: Three electronic databases (Medline, Embase, Cochrane) were
used to search the latent studies which investigated the effects of enteral
immunonutrition (EIN) compared with standard enteral nutrition (EN) or parenteral
immunonutrition (PIN) compared with standard parenteral nutrition (PN) on
colorectal cancer patients who are undergoing surgery until 21st of April, 2017.
Meta-analysis was conducted to calculate odd risk (OR), mean difference (MD), or
standard mean difference (SMD) with 95% confidence interval (CI), and
heterogeneity was tested by Q test. RESULTS: Nine publications were included. The
meta-analysis results presented that EIN improved the length of hospital stay
(pooled MD, 2.53; 95% CI, 1.29-3.41), infectious complications (pooled OR, 0.33;
95% CI, 0.21-0.53) which contains the Surgical Site Infections (pooled OR, 0.25;
95% CI, 0.22-0.58) and Superficial/Deep incisional infections (pooled OR, 0.27;
95% CI, 0.12-0.64); meanwhile, PIN improved the length of hospital stay (pooled
MD, 2.66; 95% CI, 0.62-4.76), IL-6 (pooled MD, - 6.09; 95% CI, - 10.11 to -
2.07), CD3 (pooled MD, 7.50; 95% CI, 3.57-11.43), CD4 (pooled MD, 5.47; 95% CI,
2.54-8.40), and CD4/CD8 (pooled MD, 0.50; 95% CI, 0.22-0.78); the level of CD8
was lower (pooled MD, - 4.32; 95% CI, - 7.09 to - 1.55) in PIN. CONCLUSION:
Immunonutrition could be an effective approach to enhance the immune function of
colorectal cancer patients undergoing elective surgery and to improve the
clinical and laboratory outcomes.
PMID- 29335840
TI - Efficacy of ultrasound-guided axillary/subclavian venous approaches for pacemaker
and defibrillator lead implantation: a randomized study.
AB - PURPOSE: Subclavian access is a reliable technique for lead insertion in
pacemaker and defibrillator (ICD) implantation, but it is often accompanied by
complications. The aim of this study was to compare the efficacy of the
ultrasound-guided axillary approach to the subclavian method. METHODS: This
randomized comparative study was performed on 174 patients: as a first attempt,
116 patients underwent the ultrasound-guided axillary access and 58 patients
underwent the subclavian approach. A total of 364 leads were placed. Operators
were trained in ultrasound-guided vein access technique. RESULTS: Axillary access
was successful in 69% of patients (32/46), in the training phase and, as a first
attempt, in 91.4% of patients (106/116), in the randomized phase. When axillary
approach failed, we performed the following: subclavian access in 5.2% of
patients (6/116), cephalic approach in 2.6% of patients (3/116), surgical method
in 0.9% of patients (1/116). The subclavian technique was effective, as a first
attempt, in 55 patients (94.8%). When the subclavian access failed, the
ultrasound axillary approach successfully performed in all three cases. During a
mean follow-up of 18 +/- 6 months, the number of lead complications was similar
in the subclavian group compared to the axillary group (p = 0.664). CONCLUSIONS:
As first attempt, ultrasound-guided axillary method showed similarly high-success
rate than subclavian approach and well performed when the first attempt in
subclavian group failed. Axillary access can be considered a safe and effective
alternative technique to the conventional subclavian method for device
implantation.
PMID- 29335842
TI - Direct repression of IGF2 is implicated in the anti-angiogenic function of
microRNA-210 in human retinal endothelial cells.
AB - Pathological angiogenesis leads to the development of retinal vasculopathies and
causes severe vision impairment. Increased understanding of the mechanisms
underlying the angiogenic behavior of retinal endothelial cells helps provide new
insights for developing treatment of retinal vasculopathies. Pro-angiogenic
function of miR-210 has previously been identified. However, the functional
implication of miR-210 in retinal endothelial cells remains unknown. Human
retinal microvascular endothelial cells (HRECs) were employed to investigate the
impact of miR-210 on the angiogenic capacity of retinal endothelial cells. It was
observed that without affecting the viability of HRECs, miR-210 significantly
suppressed the migration and capillary-like tube formation in HRECs. Moreover,
pro-angiogenic insulin growth factor 2 (IGF2) was newly identified as a direct
target of miR-210 in HRECs. MiR-210 decreased the expression of IGF2 at both mRNA
and protein levels in HRECs. IGF2-simulated activation of p38 MAPK was attenuated
by miR-210 in HRECs. Recombinant IGF2 protein rescued miR-210-induced impairment
of tube formation in HRECs. Therefore, in contrast to the previously reported pro
angiogenic function of miR-210, the current work reveals novel anti-angiogenic
activity of miR-210 in HRECs. Furthermore, IGF2 is identified for the first time
as a direct target of miR-210 in HRECs, adding new mechanistic insights into the
expression regulation of pro-angiogenic IGF2 in human retinal endothelial cells.
The current work helps increase the understanding of regulatory mechanisms
underlying retinal endothelial cell physiology, justifying further evaluation for
the therapeutic implications of miR-210/IGF2 interaction in the treatment of
related retinal vasculopathies.
PMID- 29335841
TI - Reconstructing normality following the diagnosis of a childhood chronic disease:
does "rare" make a difference?
AB - : Living with a childhood chronic disease can be challenging, especially if the
diagnosis involves a rare condition. This study sought to elucidate how the
diagnosis of a rare disease, as compared to a common, chronic condition, may
influence maternal experiences of childhood illness. We conducted face-to-face,
semi-structured interviews with 26 mothers of children treated in a pediatric
hospital in the province of Lecco, Italy. Half of the participants had a child
diagnosed with Bartter syndrome (BS), and the rest had a child suffering from
celiac disease (CD). Interviews were recorded, transcribed, and analyzed using an
inductive thematic approach. We identified three main themes from the analysis of
our data: (1) disrupted normality and the need to know, (2) reconstructing
normality, and (3) acting "normal." Although most participants experienced the
disclosure of diagnosis as a relief, processes that facilitated normality
reconstruction in celiac families, notably access to appropriate information,
social support, and personal contact with comparison others, were found to be
important stressors for mothers living with BS. CONCLUSION: This comparative
qualitative study provides evidence on how well-known problems associated with
the rarity of childhood diseases impact on families' efforts to cope with the
illness and regain a sense of normality. What is Known: * Families living with a
rare disease have been found to experience a range of common problems, directly
linked to the rarity of these pathologies. What is New: * Maximization of both
emotional and instrumental social support, through provision of appropriate
information or establishment of disease-specific support groups, could greatly
contribute to rare disease families' efforts to cope with childhood illness and
regain a sense of normality.
PMID- 29335843
TI - Study on the Clinical Features and Prognosis of Penicilliosis marneffei Without
Human Immunodeficiency Virus Infection.
AB - OBJECTIVE: To improve the diagnosis and treatment of Penicilliosis marneffei
without human immunodeficiency virus infection. METHODS: Analyze and review the
clinical features, diagnosis and treatment of six cases of P. marneffei without
human immunodeficiency virus infection at The First Affiliated Hospital of Fujian
Medical University. RESULTS: Two cases were diagnosed in the ENT Department,
three cases in the respiratory department and one case in the dermatological
department. Penicillium marneffei infection was confirmed by sputum culture,
blood culture and tissue biopsy. After definite diagnosis, one refused further
treatment, and others showed significant improvement. CONCLUSION: Penicilliosis
marneffei is insidious onset and easy to be escaped and misdiagnosed. To achieve
early diagnosis and appropriate treatment, doubtful cases should be alerted for
the diagnoses as P. marneffei.
PMID- 29335844
TI - The Adiponectin Homolog Osmotin Enhances Neurite Outgrowth and Synaptic
Complexity via AdipoR1/NgR1 Signaling in Alzheimer's Disease.
AB - Alzheimer's disease is a major neurodegenerative disease characterized by memory
loss and cognitive deficits. Recently, we reported that osmotin, which is a
homolog of adiponectin, improved long-term potentiation and cognitive functions
in Alzheimer's disease mice. Several lines of evidence have suggested that Nogo-A
and the Nogo-66 receptor 1 (NgR1), which form a complex that inhibits long-term
potentiation and cognitive function, might be associated with the adiponectin
receptor 1 (AdipoR1), which is a receptor for osmotin. Here, we explore whether
osmotin's effects on long-term potentiation and memory function are associated
with NgR1 signaling via AdipoR1 in Alzheimer's disease. Osmotin reduced the
expression of NgR1 without affecting Nogo-A expression. Furthermore, osmotin
inhibited NgR1 signaling by prohibiting the formation of the Nogo-A and NgR1
ligand-receptor complex, resulting in enhanced neurite outgrowth; these effects
disappeared in the presence of AdipoR1 interference. In addition, osmotin
increased the expression of the pre- and postsynaptic markers synaptophysin and
PSD-95, as well as the activation of the memory-associated markers AMPA receptor
and CREB; these effects occurred in an AdipoR1- and NgR1-dependent manner.
Osmotin was also found to enhance dendritic complexity and spine density in the
hippocampal region of Alzheimer's disease mouse brains. These results suggest
that osmotin can enhance neurite outgrowth and synaptic complexity through
AdipoR1 and NgR1 signaling, implying that osmotin might be an effective
therapeutic agent for Alzheimer's disease and that AdipoR1 might be a crucial
therapeutic target for neurodegenerative diseases such as Alzheimer's.
PMID- 29335847
TI - Diabetes, Obesity, and the Metabolic Syndrome as Prognostic Factors in Stages I
to III Colorectal Cancer Patients.
AB - BACKGROUND: Attempts to introduce prognostic factors for survival outcomes in
localized colorectal cancer patients receiving surgical treatment with or without
adjuvant therapies, beyond the classic staging parameters, have been met with
limited success. Obesity and diabetes mellitus are among the conditions that
predispose to colorectal cancer but their value as prognostic markers once the
disease is diagnosed is controversial. PATIENTS AND METHODS: This study examines
the prognostic value of the components of metabolic syndrome in a retrospective
series of colorectal cancer patients with stages I to III disease followed in a
single center. RESULTS: Among the four components of the metabolic syndrome, only
diabetes was independently associated with progression-free survival (PFS) while
obesity, hypertension, and dyslipidemia were not. No associations of the
metabolic syndrome (MS) or its components with overall survival (OS) were
observed in multivariate analysis. CONCLUSION: These data pinpoint to diabetes
mellitus (DM) as a possible prognostic factor for PFS in localized colorectal
cancer and further cast doubt for the value of obesity as measured by body mass
index (BMI) on local stage colorectal cancer prognosis.
PMID- 29335849
TI - Differential expression of adipokines in knee osteoarthritis patients with and
without metabolic syndrome.
AB - PURPOSE: The purpose of this study was to compare adipokines levels in plasma and
synovial fluid (SF) between knee osteoarthritis (OA) patients with and without
metabolic syndrome (MetS), and to evaluate the associations between adipokines
levels and clinical severity of knee osteoarthritis. METHODS: Eighty female
patients with knee osteoarthritis were enrolled in the study. These patients were
divided into two groups: patients with and without MetS. Clinical severity was
evaluated according to visual analogue scale (VAS) pain scores and Western
Ontario McMaster University Osteoarthritis Index (WOMAC) scores. Adipokines and
soluble leptin receptor levels in plasma and SF were determined by a sandwich
enzyme-linked immunosorbent assay. RESULTS: Forty-three (54%) osteoarthritis
patients with MetS and 37 (46%) osteoarthritis patients without MetS were
enrolled as MetS-OA group and nMetS-OA group, respectively. VAS pain and WOMAC
scores were higher in MetS-OA group compared with those in nMets-OA group (p <
0.01). The leptin and free leptin levels in plasma and SF were significantly
higher in MetS-OA group than those in nMetS-OA group, while the adiponectin
levels were lower (All p < 0.01). Significant differences existed even after
adjustment for body mass index (BMI) (p < 0.05). There were no significant
associations between adipokines levels and the clinical severity of OA in MetS-OA
group and nMetS-OA group respectively (p > 0.05). CONCLUSIONS: Leptin was higher
and adiponectin was lower in knee osteoarthritis patients with MetS compared to
those without MetS, independent of BMI. The higher SF and plasma levels of leptin
in MetS-OA patients may need further studies to delineate their
pathophysiological relationships.
PMID- 29335845
TI - Carnosic Acid as a Promising Agent in Protecting Mitochondria of Brain Cells.
AB - Carnosic acid (CA; C20H28O4), a phenolic diterpene characterized as an ortho
dihydroquinone-type molecule, is a pro-electrophile agent that becomes an
electrophile after reacting with free radicals. The electrophile generated from
CA interacts with and activates the nuclear factor erythroid 2-related factor 2
(Nrf2) transcription factor, which is a major modulator of redox biology in
mammalian cells. CA induces antioxidant and anti-inflammatory effects in several
cell types, as observed in both in vitro and in vivo experimental models. In this
context, CA has been viewed as a neuroprotective agent by activating signaling
pathways associated with cell survival during stressful conditions. Indeed, CA
exhibits the ability to promote mitochondrial protection in neural cells.
Mitochondria are the main source of both ATP and reactive species in animal
cells. Mitochondrial dysfunction plays a central role in the start and
development of neurodegenerative disorders, such as Alzheimer's disease,
Parkinson's disease, and Huntington's disease, among others. Therefore, the study
of strategies aiming to reduce mitochondrial impairment in the case of
neurodegeneration is of pharmacological interest. In the present review, it is
described and discussed the effects of CA on brain mitochondria in experimental
models of neural lesion. Based on the data discussed here, CA is a potential
candidate to be listed as a neuroprotective agent by acting on the mitochondria
of neural cells.
PMID- 29335850
TI - Functional outcome after endoscopic assisted release of the ulnar nerve for
cubital tunnel syndrome: mid-to-long term results.
AB - AIM OF THE STUDY: The aim of the study was to investigate functional and patient
rated outcome parameters after endoscopic assisted release of the ulnar nerve for
cubital tunnel syndrome. METHODS: One hundred of 204 consecutive patients between
2006 and 2011 met the inclusion/exclusion criteria. Fifty-one of these patients
were recruited and evaluated clinically and by questionnaire testing
retrospectively after a mean follow-up of 82 months (range: 60-116). RESULTS:
Neurological parameters (two-point-discrimination, application of Semmes
Weinstein monofilaments, Tinel's test), grip, and three-point pinch strength were
not significantly different from the contralateral extremity at the time of
examination, whereas key pinch strength was significantly weaker. Mean
Disabilities of the Arm, Shoulder, and Hand score was 20.82. Patients' overall
opinion was good/excellent for 78% of the study population. DISCUSSION: The
examined surgical procedure proved to be as efficacious as open in-situ
decompression regarding functional outcome with fewer post-operative
complications. Regarding the results it might be postulated that grip strength
and three-point pinch strength determination is not necessarily relevant for
ulnar nerve evaluation. CONCLUSION: Endoscopic assisted release of the ulnar
nerve is a reliable and safe treatment option for cubital tunnel syndrome with
satisfactory mid-to-long term functional and patient-rated outcomes.
PMID- 29335846
TI - Cotinine: A Therapy for Memory Extinction in Post-traumatic Stress Disorder.
AB - Post-traumatic stress disorder (PTSD) is a mental disorder that may develop after
exposure to exceptionally threatening or unescapable horrifying events. Actual
therapies fail to alleviate the emotional suffering and cognitive impairment
associated with this disorder, mostly because they are ineffective in treating
the failure to extinguish trauma memories in a great percentage of those
affected. In this review, current behavioral, cellular, and molecular evidence
supporting the use of cotinine for treating PTSD are reviewed. The role of the
positive modulation by cotinine of the nicotinic acetylcholine receptors (nAChRs)
and their downstream effectors, the protection of astroglia, and the inhibition
of microglia in the PTSD brain are also discussed.
PMID- 29335851
TI - The relation between personality, informal caregiving, life satisfaction and
health-related quality of life: evidence of a longitudinal study.
AB - PURPOSE: Personality characteristics of the caregiver might play a role in the
relation between informal caregiving and health-related quality of life as well
as life satisfaction. However, a limited body of research has examined this
relation. This study aimed to examine the role personality characteristics of the
caregiver might play in the relation between informal caregiving and well-being
outcomes using a longitudinal approach. METHODS: Data were derived from the large
Panel 'Labour Market and Social Security.' This is an annual household survey,
which is conducted by order of the Institute for Employment Research covering
persons and households registered as residents of Germany. The SF-12 was used to
capture health-related quality of life (covering physical and mental health). A
short version of the Big Five Inventory (BFI-K) was used to quantify personality
factors. Life satisfaction was measured by a single-item measure. Concentrating
on these factors, we used data from the third (2008/2009), sixth (2012), and
ninth wave (2015). 34,548 observations were used in fixed effects regressions.
RESULTS: Adjusting for various potential confounders, linear fixed effects
regressions showed that the onset of informal caregiving reduced life
satisfaction (beta = - .14, p < .01), but not physical and mental health. The
relation between informal caregiving and life satisfaction was significantly
moderated by agreeableness (p < .01). CONCLUSIONS: Findings of the present study
emphasized that agreeableness moderates the relationship between informal
caregiving and life satisfaction. Measuring personality characteristics of the
informal caregiver is important for tailoring interventional strategies in order
to increase the benefit of these programs.
PMID- 29335852
TI - Authors' reply to "Rectal sparing approach after preoperative radio- and/or
chemotherapy (RESARCH) in patients with rectal cancer: potential pitfalls of a
multicentre observational study".
PMID- 29335853
TI - Effect of nonwoven jute agrotextile mulch on soil health and productivity of
broccoli (Brassica oleracea L.) in lateritic soil.
AB - A field experiment was conducted in winter season of 2015-2016 in the dry
lateritic soil of Eastern India to study the effect of different thicknesses of
nonwoven jute agrotextile mulches (NJATM) along with other mulches on soil
health, growth and productivity of broccoli (Brassica oleracea L.). The
experiment was conducted in randomized block design with six treatments viz., T1
(control, i.e. no mulching), T2 (300 gsm NJATM), T3 (350 gsm NJATM), T4 (400 gsm
NJATM), T5 (rice straw) and T6 (black polythene mulch), each of which was
replicated four times. The highest average curd weight (355.25 g) and yield (8.53
t ha-1) of broccoli were recorded in T3 treatment. The lowest density of broad
leaved weed, sedges and grasses were recorded in T6 treatment which was
statistically at par with T4. All the treatments composing of NJATM increased the
population of all the soil microbes except bacteria in the root rhizosphere of
broccoli from their initial population. On average, the highest population of
fungi (54.0 * 103 cfu per g) and actinomycetes (134.75 * 103 cfu per g) was
recorded with T3 and T4 treatments respectively in the post-harvest soil. The
soil moisture was conserved in all treatments compared to control showing highest
moisture content in T4 treatment. Organic carbon and available N, P and K
contents of soil were increased in all mulch treated plots compared to control,
and their initial value and their highest value were recorded in T3. The NJATM of
350 gsm thickness was very effective compared to other mulches in increasing the
growth and productivity of broccoli by suppressing weeds, increasing moisture,
microbial population and nutrient content of the lateritic soil.
PMID- 29335854
TI - Nonreconstruction Options for Treating Medial Ulnar Collateral Ligament Injuries
of the Elbow in Overhead Athletes.
AB - PURPOSE OF REVIEW: This review aims to describe the nonreconstructive options for
treating ulnar collateral ligament (UCL) injuries ranging from nonoperative
measures, including physical therapy and biologic injections, to ligament repair
with and without augmentation. RECENT FINDINGS: Nonoperative options for UCL
injuries include guided physical therapy and biologic augmentation with platelet
rich plasma (PRP). In some patients, repair of the UCL has shown promising return
to sport rates by using modern suture and suture anchor techniques. Proximal
avulsion injuries have shown the best results after repair. Currently, there is
growing interest in augmentation of UCL repair with an internal brace. The
treatment of UCL injuries involves complex decision making. UCL reconstruction
remains the gold standard for attritional injuries and complete tears, which
occur commonly in professional athletes. However, nonreconstructive options have
shown promising results for simple avulsion or partial thickness UCL injuries.
Future research comparing reconstructive versus nonreconstructive options is
necessary.
PMID- 29335855
TI - T cell responses to tumor: how dominant assumptions on immune activity led to a
neglect of pathological functions, and how evolutionary considerations can help
identify testable hypotheses for improving immunotherapy.
AB - Cancer immunotherapy is based on the premise that activated, pro-inflammatory T
cell responses to tumor will mostly combat tumor growth. Nowadays accepted as
largely valid, this hypothesis has been formed as a result of extensive
theoretical and experimental argumentation on the inherent function of the immune
system and the nature of the immunological self, dating back to the foundations
of immunology. These arguments have also been affected by how current working
hypotheses were set by researchers, an issue that has been the focus of study by
medical anthropologists. As a result of these processes, cancer immunotherapy has
developed into a truly promising anti-cancer strategy, with very substantial
benefits in clinical outcomes. However, as immunotherapy still has large margins
for improvement, a more thorough examination of both the historical background
and evolutionary context of current assumptions for how the immune system
responds to cancer can help reveal novel, testable questions. We describe how
attempting to answer some of these questions experimentally, such as identifying
the contributors of tumor-associated fibrosis, has led to potentially useful
insights on how to improve immunotherapy.
PMID- 29335856
TI - Abscopal effects of radiotherapy and combined mRNA-based immunotherapy in a
syngeneic, OVA-expressing thymoma mouse model.
AB - BACKGROUND: Tumor metastasis and immune evasion present major challenges of
cancer treatment. Radiotherapy can overcome immunosuppressive tumor
microenvironments. Anecdotal reports suggest abscopal anti-tumor immune
responses. This study assesses abscopal effects of radiotherapy in combination
with mRNA-based cancer vaccination (RNActive(r)). METHODS: C57BL/6 mice were
injected with ovalbumin-expressing thymoma cells into the right hind leg (primary
tumor) and left flank (secondary tumor) with a delay of 4 days. Primary tumors
were irradiated with 3 * 2 Gy, while secondary tumors were shielded. RNA and
combined treatment groups received mRNA-based RNActive(r) vaccination. RESULTS:
Radiotherapy and combined radioimmunotherapy significantly delayed primary tumor
growth with a tumor control in 15 and 53% of mice, respectively. In small
secondary tumors, radioimmunotherapy significantly slowed growth rate compared to
vaccination (p = 0.002) and control groups (p = 0.01). Cytokine microarray
analysis of secondary tumors showed changes in the cytokine microenvironment,
even in the non-irradiated contralateral tumors after combination treatment.
CONCLUSION: Combined irradiation and immunotherapy is able to induce abscopal
responses, even with low, normofractionated radiation doses. Thus, the
combination of mRNA-based vaccination with irradiation might be an effective
regimen to induce systemic anti-tumor immunity.
PMID- 29335857
TI - Effect of soothing Gan (Liver) and invigorating Pi (Spleen) recipes on TLR4-p38
MAPK pathway in kupffer cells of non-alcoholic steatohepatitis rats.
AB - OBJECTIVE: To investigate the mechanism of inflammatory-mediated toll-like
receptor 4 (TLR4)-p38 mitogen-activated protein kinase (p38 MAPK) pathway in
Kupffer cells (KCs) of non-alcoholic steatohepatitis (NASH) rats and the
intervention effect of soothing Gan (Liver) and invigorating Pi (Spleen) recipes
on this pathway. METHODS: After 1 week of acclimatization, 120 Sprague-Dawley
male rats were randomly divided into 8 groups using a random number table (n=15
per group): normal group, model group, low-dose Chaihu Shugan Powder (, CHSG)
group (3.2 g/kg), high-dose CHSG group (9.6 g/kg), low-dose Shenling Baizhu
Powder (, SLBZ) group (10 g/kg), high-dose SLBZ (30 g/kg) group, and low-and
highdose integrated recipe (L-IR, H-IR) groups. All rats in the model and
treatment groups were fed with a high-fat diet (HFD). The treatments were
administrated by gastrogavage once daily and lasted for 26 weeks. The liver
tissues were detected with hematoxylin-eosin (HE) and oil red O staining. Levels
of liver lipids, serum lipids and transaminases were measured. KCs were isolated
from the livers of rats to evaluate the mRNA expressions of TLR4 and p38 MAPK by
real-time flfl uorescence quantitative polymerase chain reaction, and proteins
expressions of TLR4, p-p38 MAPK and p38 MAPK by Western blot. Levels of
inflammatory cytokines including tumor necrosis factor alpha (TNF-alpha),
interleukin (IL)-1 and IL-6 in KCs were measured by enzyme-linked immunosorbent
assay. RESULTS: After 26 weeks of HFD feeding, HE and oil red O staining showed
that the NASH model rats successfully reproduced typical pathogenesis and
histopathological features. Compared with the normal group, the model group
exhibited signifificant increases in body weight, liver weight, liver index,
serum levels of total cholesterol (TC), triglyceride (TG), low-density
lipoprotein cholesterol, and aspartate aminotransferase as well as TC and TG
levels in liver tissues, and significant decrease in serum level of high-density
lipoprotein cholesterol (P<0.05 or P<0.01), while those indices were
significantly ameliorated in the H-IR group (P<0.05 or P<0.01). Higher levels of
TNF-alpha, IL-1 and IL-6 in KCs were observed in the model group compared with
the normal group (P<0.01). Signifificant decreases in TNF-alpha, IL-1 and IL-6
were observed in the H-SLBZ, H-IR and L-IR groups compared with the model group
(P<0.05 or P<0.01). The mRNA expressions of TLR4 and p38 MAPK and protein
expressions of TLR4, p38 MAPK and p-p38 MAPK in KCs in the model group were
signifificantly higher than the normal group (P<0.01), while those expression
levels in the L-IR and H-IR groups were signifificantly lower than the model
group (P<0.05 or P<0.01). CONCLUSIONS: Inflfl ammation in KCs might play an
important role in the pathogenesis of NASH in rats. The data demonstrated the
importance of TLR4-p38MAPK signaling pathway in KCs for the anti-inflfl ammatory
effect of soothing Gan and invigorating Pi recipes.
PMID- 29335858
TI - Effects of Aidi injection () with Western medical therapies on quality of life
for patients with primary liver cancer: a systematic review and meta-analysis.
AB - OBJECTIVE: To evaluate the effects of Aidi Injection (, AD) in combination with
Western medical therapies (WMT) in patients with primary liver cancer (PLC).
METHODS: Randomized controlled trials (RCTs) comparing AD plus WMT with WMT alone
were retrieved from inception to March 2013 by retrieving the literature database
thoroughly and systematically. The extracted data from included studies were
analyzed and synthesized by Review Manager 5.2 software. The Cochrane risk of
bias tool was used to assess the quality of included studies, and Begg's and
Egger's tests were used to evaluate the potential presence of publication bias.
The studies were divided into 7 separate subgroups in terms of quality of life
(QOL), recent chemotherapy and the incidence of leukocyte reduction. The subgroup
analysis was applied to assess the heterogeneity between included researches, and
the sensitivity analysis was used to weigh the stability of studies. RESULTS:
Twenty-four RCTs were included in this study. Compared with WMT used alone, AD as
additional intervention was more effective on improving QOL (P<0.01), increasing
short-term effificacy (P<0.01), prolonging life (P<0.05 or P<0.01), relieving
clinical symptoms (P<0.01), and reducing adverse events (e.g. reduce white blood
cell counts, P=0.002; reduce in platelet counts, P<0.01). Subgroup analysis
showed that the hepatic artery interventions with AD was superior in improving
QOL (P<0.01) and enhancing short-term response rates (P=0.007) and reducing white
blood cell counts (P=0.0004) than hepatic artery interventions alone (P<0.01).
The chemoembolization plus AD or the chemotherapy plus AD were both better than
chemoembolization or the chemotherapy alone in improving the QOL and short-term
response rate (P<0.05 or P<0.01). CONCLUSIONS: AD in combination with WMT
improves QOL in patients with PLC. Considering the inherent limitations of the
included studies, further well-designed, rigorously performed, high-quality, and
double-blinded RCTs with large sample sizes are needed.
PMID- 29335859
TI - Arginine vasopressin-aquaporin-2 pathway-mediated dehydration effects of
electroacupuncture in guinea pig model of AVP-induced endolymphatic hydrops.
AB - OBJECTIVE: To investigate the effects of electroacupuncture (EA) on endolymphatic
hydrops (EH) and the regulation of arginine vasopressin (AVP)-aquaporin-2 (AQP2)
pathway in guinea pigs. METHODS: EH was induced in male guinea pigs by an
intraperitoneal injection of AVP. For the treatment, EA was delivered to Baihui
(GV 20) and Tinggong (SI 19) acupoints, once per day for 10 consecutive days. In
histomorphological studies, cochlear hydrops degree was evaluated by hematoxylin
eosin (HE) staining, and then the ratio of scala media (SM) area to SM + scala
vestibuli (SV) area (R value) was calculated. In mechanical studies, a comparison
of plasma AVP (p-AVP) concentrations, cyclic adenosine monophosphate (cAMP)
levels, vasopressin type 2 receptor (V2R) and AQP2 mRNA expressions in the
cochlea were compared among groups. RESULTS: EA significantly reduced cochlear
hydrops in guinea pigs (P=0.001). EA significantly attenuated the AVPinduced up
regulation of p-AVP concentrations (P=0.006), cochlear cAMP levels (P=0.003) and
AQP2 mRNA expression (P=0.016), and up-regulated the expression of V2R mRNA
(P=0.004) in the cochlea. CONCLUSIONS: The dehydrating effect of EA might be
associated with its inhibition of AVP-AQP2 pathway activation.
PMID- 29335860
TI - Effectiveness and safety of Chinese medicine for Idiopathic pulmonary fibrosis: A
systematic review and meta-analysis.
AB - OBJECTIVE: To evaluate the effectiveness and safety of Chinese medicine (CM) for
Idiopathic pulmonary fifibrosis (IPF) patients. METHODS: To screened relevant
articles, PubMed, Cochrane Library, Excerpta Medica Datase (EMBASE), China
National Knowledge Infrastructure (CNKI), Chinese VIP Information (VIP), Wanfang
Database and Chinese Biomedical Database (CBM) were searched in English or
Chinese until December 2015 for randomized controlled trials, which compared CM
treatment (CM group) with Western medicine or placebo (control group) on IPF. The
outcome measures included acute exacerbation, pulmonary function, the St George's
respiratory questionnaire (SGRQ) scores, 6-minute walk test (6MWT) distance,
adverse events and mortality. RESULTS: This meta-analysis included 25 randomized
controlled trials involving 1,471 patients. Compared with the control group, CM
group was superiori in reducing the risk of exacerbation [relative risk
(RR)=0.40, 95% CI 0.22 to 0.72, P<0.05], improving in forced expiratory volume in
one second (FEV1) [standard mean difference (SMD)=0.62, 95% CI 0.40 to 0.84,
P<0.01] and diffusion capacity for carbon monoxide (DLCO, SMD=0.40, 95% CI 0.22
to 0.58, P<0.01), but there was no significant difference in vital capacity (VC,
SMD=0.10, 95% CI-0.12 to 0.31, P>0.05). This meta-analysis also revealed that CM
therapy signifificantly decreased the SGRQ score (SMD=-0.60, 95% CI-1.14 to-0.05,
P<0.05) and improved 6MWT distance (SMD=0.59, 95% CI 0.34 to 0.84, P<0.01),
compared with the control group. Meanwhile, CM therapy was associated with a low
incidence of adverse effects (RR=0.19, 95% CI 0.08 to 0.43, P<0.01). However,
there was no signifificant difference in mortality (RR=0.24, 95% CI 0.05 to 1.10,
P>0.05) between CM and control groups. CONCLUSIONS: The pooled outcomes suggest
that CM treatment appears benefifit in reducing the risk of exacerbation,
improving lung function and decreasing the incidence of adverse effects and
enhancing the quality of life. However, the outcomes were limited because of the
low quality of the included studies. More rigorous clinic trials need to be
carried out to provide suffificient and accurate evidence in the future.
PMID- 29335862
TI - Rules of meridians and acupoints selection in treatment of Parkinson's disease
based on data mining techniques.
AB - OBJECTIVE: To help selecting appropriate meridians and acupoints in clinical
practice and experimental study for Parkinson's disease (PD), the rules of
meridians and acupoints selection of acupuncture and moxibustion were analyzed in
domestic and foreign clinical treatment for PD based on data mining techniques.
METHODS: Literature about PD treated by acupuncture and moxibustion in China and
abroad was searched and selected from China National Knowledge Infrastructure and
MEDLINE. Then the data from all eligible articles were extracted to establish the
database of acupuncture-moxibustion for PD. The association rules of data mining
techniques were used to analyze the rules of meridians and acupoints selection.
RESULTS: Totally, 168 eligible articles were included and 184 acupoints were
applied. The total frequency of acupoints application was 1,090 times. Those
acupoints were mainly distributed in head and neck and extremities. Among all,
Taichong (LR 3), Baihui (DU 20), Fengchi (GB 20), Hegu (LI 4) and Chorea-tremor
Controlled Zone were the top five acupoints that had been used. Superior-inferior
acupoints matching was utilized the most. As to involved meridians, Du Meridian,
Dan (Gallbladder) Meridian, Dachang (Large Intestine) Meridian, and Gan (Liver)
Meridian were the most popular meridians. CONCLUSIONS: The application of
meridians and acupoints for PD treatment lay emphasis on the acupoints on the
head, attach importance to extinguishing Gan wind, tonifying qi and blood, and
nourishing sinews, and make good use of superior-inferior acupoints matching.
PMID- 29335863
TI - Integrative medicine on optimizing clopidogrel and aspirin therapy.
AB - This article reviews the available published data on optimizing clopidogrel and
aspirin therapy using translational and integrative medicine. Translational and
evidence-based medical studies show that the CYP2C19 gene mutation (CYP2C19*2 and
CYP2C19*3) could affect > 50% of the Chinese population, and that this mutation
is closely associated with clopidogrel resistance and an increased risk of major
adverse cardiovascular events, particularly stent thrombosis in patients
following percutaneous coronary intervention (PCI). Adjusted-dose warfarin and
aspirin reduce stroke in patients with atrial fibrillation (AF), and warfarin is
substantially more efficacious than aspirin. However, a poor compliance is a big
problem in warfarin use especially in China. The genetic variants of vitamin K
expoxide reductase might account for the universally lower warfarin dosage used
in Chinese population. The available evidence indicates that the integrating
mainstream treatments (e.g., clopidogrel, CYP2C19 genotyping) and non-mainstream
medicines [e.g., Chinese medicines, Naoxintong Capsule (, NXT)] to treat CYP2C19
gene mutation patients following PCI can be effective. Aspirin combined NXT and
the adjusted-dose warfarin was equally effective in elderly patients with non
valvular AF in prevention of ischemic stroke.
PMID- 29335861
TI - Alterations of Gefitinib Pharmacokinetics by Co-administration of Herbal
Medications in Rats.
AB - OBJECTIVE: To evaluate the potential pharmacokinetic interactions of the
anticancer agent gefitinib (Iressa(r)) and the oriental medications Guipi
Decoction (, GPD, Guibi-tang in Korean) and Bawu Decoction (, BWD, Palmul-tang in
Korean). METHODS: Methylcellulose (MC, control), GPD (1,200 mg/kg), or BWD (6,000
mg/kg) was orally administered to rats either as a single dose or multiple doses
prior to gefitinib administration. To examine the effects of a single dose of the
herbal medicines, gefitinib (10 mg/kg) was orally administered after 5 min or 1 h
of MC or the herbal medicine pretreatments. To examine the effects of the
multiple doses of the herbal medicines, gefitinib (10 mg/kg) was orally
administered following 7 consecutive days of the administration of MC or each
herbal medicine. The plasma concentrations of gefitinib were determined with
liquid chromatography-tandem mass spectrometry assay. The plasma concentration
time profiles of gefitinib were analyzed with a noncompartmental analysis.
RESULTS: Gefitinib was rapidly absorbed and showed a monoexponential decline with
an elimination half-life of 3.7-4.1 h. The pharmacokinetics of gefitinib was not
affected by GPD pretreatment. However, a significantly lower maximum plasma
concentration (Cmax, P<0.05) and area under the curve (P<0.05), and a delayed
time to reach Cmax (Tmax, P<0.01) were observed in both single- and multipledose
BWD-pretreated rats compared with the control rats. CONCLUSIONS: BWD and not GPD
might delay and interfere with gefitinib absorption. Further evaluations of the
clinical significance of these findings are needed.
PMID- 29335864
TI - Ethanol Extract of Lycopodium serratum Thunb. Attenuates Lipopolysaccharide
Induced C6 Glioma Cells Migration via Matrix Metalloproteinase-9 Expression.
AB - OBJECTIVE: To elucidate how ethanol extract of L. serratum (ELS) could exert anti
migratory effects on glioma with the suppression of nuclear factor kappa B (NF
kappaB) downstream pathway. METHODS: Cell viability of ELS on C6 glioma was
detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
assay. Nitric oxide (NO) assay and 2',7'-dichlorofluorescin diacetate (DCFH-DA)
assay were applied to measure NO production and reactive oxygen species (ROS)
generation on lipopolysaccharide (LPS)-induced C6 glioma cells. NF-kappaB,
mitogen-activated protein kinase (MAPK), inducible nictric oxide synthase (iNOS)
and cyclooxygenase-2 (COX-2) protein were determined by Western blot. Wound
healing assay was used to investigate the inhibitory effect of ELS on fetal
bovine serum (FBS)-induced migration and matrix metalloproteinase (MMP)-9 and -2
activity was examined by zymography. RESULTS: ELS suppressed LPS-induced
phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal
kinase (JNK), and p38 through inhibiting the expression of chemokine CCL2 (or
monocyte chemoattractant protein-1, MCP-1). In addition, ELS inhibited the
expression of iNOS, COX-2, and the production of NO by LPS in C6 glioma cells.
ELS also significantly decreased serum-induced migration of C6 glioma cells in
scratch wound healing in a dose-dependent manner (P<0.01). The activity of MMP-9
and -2 were also significantly attenuated by ELS with LPS treatment (P<0.01).
CONCLUSIONS: Our results suggest that downregulation of MMP-9 gene expression
might be involved in the anti-migration effect of ELS against LPS-induced C6
glioma cells.
PMID- 29335865
TI - Beneficial Effect of Berberis amurensis Rupr. on Penile Erection.
AB - OBJECTIVE: To investigate whether the methanol extract of Berberis amurensis
Rupr. (BAR) augments penile erection using in vitro and in vivo experiments.
METHODS: The ex vivo study used corpus cavernosum strips prepared from adult male
New Zealand White rabbits. In in vivo studies for intracavernous pressure (ICP),
blood pressure, mean arterial pressure (MAP), and increase of peak ICP were
continuously monitored during electrical stimulation of Sprague-Dawley rats.
RESULTS: Preconstricted with phenylephrine (PE) in isolated endotheliumintact
rabbit corus cavernosum, BAR relaxed penile smooth muscle in a dose-dependent
manner, which was inhibited by pretreatment with NG-nitro-L-arginine methyl ester
(L-NAME), a nitric oxide synthase inhibitor, and 1H-[1,2,4]-oxadiazole-[4,3
alpha]-quinoxalin-1-one, a soluble guanylyl cclase inhibitor. BAR significantly
relaxed penile smooth muscles dose-dependently in ex vivo, and this was inhibited
by pretreatment with L-NAME 1H-[1,2,4]-oxadiazole-[4,3-alpha]-quinoxalin-1-one.
BAR-induced relaxation was significantly attenuated by pretreatment with
tetraethylammonium (TEA, P<0.01), a nonselective K+ channel blocker, 4
aminopyridine (4-AP, P<0.01), a voltage-dependent K+ channel blocker, and
charybdotoxin (P<0.01), a large and intermediate conductance Ca2+ sensitive-K+
channel blocker, respectively. BAR induced an increase in peak ICP, ICP/MAP ratio
and area under the curve dose dependently. CONCLUSION: BAR augments penile
erection via the nitric oxide/cyclic guanosine monophosphate system and Ca2+
sensitive-K+ (BKCa and IKCa) channels in the corpus cavernosum.
PMID- 29335866
TI - Balancing Effect of Biejiajian Oral Liquid () on ACE-Ang II-AT1R Axis and ACE2
Ang-(1-7)-Mas Axis in Rats with CCl4-Induced Hepatic Fibrosis.
AB - OBJECTIVE: To explore the effect of Biejiajian Oral Liquid (, BOL) on CCl4
induced hepatic fibrosis in rats by detecting the changes in the levels of
angiotensin II (Ang II), angiotensin-(1-7) [Ang-(1-7)], angiotensin-converting
enzyme (ACE), ACE2, angiotensin II type 1 receptor (AT1R), Mas, etc. METHODS: A
total of 180 Wistar rats were randomly divided into two groups by random digital
table method: prevention experiment and treatment experiment. Each group was
further subdivided into the following 6 subgroups: normal control group, model
group, vitamin E [100 mg/(kg.d), VE] group, enalapril [10 mg/(kg.g), Ena] group,
high-dosage [20 g/(kg.d)] BOL group, and low-dosage [10 g/(kg.d)] BOL group. The
hepatic fibrosis rat model was established by subcutaneous injection of CCl4 for
6 weeks. Prevention experiment and treatment experiment were administered with
specific drugs at different times. At the end of treatment experiment, the
pathological changes of liver were observed after hematoxylin-eosin staining. The
expressions of ingredients in renin-angiotensin-aldosterone system (RAAS) such as
AngII, Ang-(1-7), ACE, ACE2, AT1R, Mas, renin, CYP11B2 and angen in liver were
detected by enzyme linked immunosorbent assay, immunohistochemistry method or
reverse transcription-polymerase chain reaction, respectively. RESULTS: The
levels of AngII and Ang-(1-7) at the 6th week increased by 496.10% and 73.64%,
respectively, compared with those at the 2nd week in the model group (P<0.01).
With prevention or treatment with high-dosage BOL, there was an evident reduction
of AngII level but an improvement of Ang-(1-7) level. Specifically, AngII level
of high-dosage group decreased by 77.50% in prevention experiment (P=0.000) and
by 76.93% in treatment experiment (P=0.002) compared with that in the model
group. Ang-(1-7) level increased by 91.69% in prevention experiment (P=0.006) and
by 70.77% in the treatment experiment (P=0.010) compared with that in the model
group. The expression levels of mRNA of renin, ACE, CYP11B2, angen and AT1R
decreased by 58.15%, 99.90%, 99.84%, 99.99% and 99.99% (all P<0.01),
respectively. CONCLUSIONS: BOL could help resist liver fibrosis in rats by
enhancing the level of each ingredient in ACE2-Ang-(1-7)-Mas axis, while
decreasing the level of each ingredient in ACE-AngII-AT1R axis. To some extent,
BOL could enhance the regulation of RAAS in rats with CCl4-induced hepatic
fibrosis.
PMID- 29335867
TI - Can CT-based radiomics signature predict KRAS/NRAS/BRAF mutations in colorectal
cancer?
AB - OBJECTIVES: To investigate whether CT-based radiomics signature can predict
KRAS/NRAS/BRAF mutations in colorectal cancer (CRC). METHODS: This retrospective
study consisted of a primary cohort (n = 61) and a validation cohort (n = 56)
with pathologically confirmed CRC. Patients underwent KRAS/NRAS/BRAF mutation
tests and contrast-enhanced CT before treatment. A total of 346 radiomics
features were extracted from portal venous-phase CT images of the entire primary
tumour. Associations between the genetic mutations and clinical background,
tumour staging, and histological differentiation were assessed using univariate
analysis. RELIEFF and support vector machine methods were performed to select key
features and build a radiomics signature. RESULTS: The radiomics signature was
significantly associated with KRAS/NRAS/BRAF mutations (P < 0.001). The area
under the curve, sensitivity, and specificity for predicting KRAS/NRAS/BRAF
mutations were 0.869, 0.757, and 0.833 in the primary cohort, respectively, while
they were 0.829, 0.686, and 0.857 in the validation cohort, respectively.
Clinical background, tumour staging, and histological differentiation were not
associated with KRAS/NRAS/BRAF mutations in both cohorts (P>0.05). CONCLUSIONS:
The proposed CT-based radiomics signature is associated with KRAS/NRAS/BRAF
mutations. CT may be useful for analysis of tumour genotype in CRC and thus
helpful to determine therapeutic strategies. KEY POINTS: * Key features were
extracted from CT images of the primary colorectal tumour. * The proposed
radiomics signature was significantly associated with KRAS/NRAS/BRAF mutations. *
In the primary cohort, the proposed radiomics signature predicted mutations. *
Clinical background, tumour staging, and histological differentiation were unable
to predict mutations.
PMID- 29335869
TI - Magnetic resonance cholangiopancreatography with GRASE sequence at 3.0T: does it
improve image quality and acquisition time as compared with 3D TSE?
AB - OBJECTIVES: The current study evaluated the clinical usefulness of the gradient
and spin-echo (GRASE) sequence with single breath-hold in 3.0 T magnetic
resonance cholangiopancreatography (MRCP). We compared the acquisition time and
image quality between GRASE and breath navigator-triggered 3D turbo spin echo (3D
TSE). METHODS: We examined 54 consecutive patients who underwent MRCP with GRASE
and 3D TSE. We compared the image acquisition time and contrast-to-noise ratio
(CNR) between the common bile duct (CBD) and liver. Overall image quality,
blurring, motion artifacts and CBD visibility were scored on a 4-point scale by
two radiologists. Paired t-tests were used to compare the variables. RESULTS: The
mean image acquisition time was 95 % shorter with the GRASE than with 3D TSE
(GRASE: 20 s; 3D TSE: 6 min 27 s). The CNR of GRASE was significantly higher than
that of 3D TSE (GRASE: 25.4 +/- 13.9 vs. 3D TSE: 18.2 +/- 9.6, p < 0.01). All
qualitative scores for GRASE were significantly better than those for 3D TSE.
CONCLUSIONS: 3.0 T MRCP with GRASE sequence with single breath-hold significantly
improved the CNR of CBD with a 95 % shorter acquisition time compared with
conventional 3D MRCP with 3D TSE. KEY POINTS: * MRCP acquisition time was 95%
shorter with GRASE than with 3D TSE. * Overall image quality of GRASE was
significantly better than 3D TSE. * Pancreaticobiliary tree visibility with GRASE
was better than that with 3D TSE.
PMID- 29335868
TI - Added value of ancillary imaging features for differentiating scirrhous
hepatocellular carcinoma from intrahepatic cholangiocarcinoma on gadoxetic acid
enhanced MR imaging.
AB - OBJECTIVES: To determine ancillary features that help distinguish between
scirrhous hepatocellular carcinoma (S-HCC) and intrahepatic cholangiocarcinoma
(ICC) and investigate added value of ancillary features to enhancement pattern
based diagnosis on gadoxetic acid-enhanced MRI. METHODS: This retrospective study
included 96 patients with S-HCCs and 120 patients with ICCs who underwent
gadoxetic acid MRI before surgical resection. Two observers reviewed MRIs of the
tumours. After determining ancillary features for differentiating tumour types,
we measured the diagnostic performance of adding ancillary features to
enhancement pattern-based diagnosis. RESULTS: T2 central darkness, capsule and
septum were significant and independent features differentiating S-HCC from ICC
(p <= .06). Adding ancillary features to enhancement pattern led to increased
accuracy (observer 1, 78.9 vs. 93.8 %; observer 2, 80.3 vs. 92.8 %; p < .001),
sensitivity (observer 1, 74.5 vs. 96.4 %; observer 2, 77.1 vs. 93.2 %; p < .001
and .001), and specificity (observer 1, 82.5 vs. 91.7 %; observer 2, 82.9 vs.
92.5 %; p = .006 and .005) for diagnosis of S-HCC by differentiation from ICC.
CONCLUSIONS: Adding ancillary features capsule, septum and T2 central darkness to
conventional enhancement patterns on gadoxetic acid-enhanced MRI improved
accuracy, sensitivity and specificity for S-HCC diagnosis with differentiation
from ICC. KEY POINTS: * Capsule, septum, and T2 central darkness were ancillary
features for S-HCC. * A typical HCC enhancement was seen in 31.3% of S-HCCs. *
Ancillary MRI features were useful in differentiation between S-HCC and ICC.
PMID- 29335870
TI - A New Species of Pararrhopalites Bonet & Tellez (Collembola, Symphypleona,
Sminthuridae) from Iron Caves in Brazil.
AB - A second species of the genus Pararrhopalites is described from caves inserted in
iron ore lithology. Both species present a particular sensory organ in the
interantennal region. The new species, Pararrhopalites ubiquum n.sp., has a wider
distribution and it is not restricted to a single cave, as it is the case of
Pararrhopalites sideroicus Zeppelini & Brito, in Fla Entomol 97(4):1733-1744,
2014, being found even in the Mesovoid Shallow Substratum. An update to the
previously published identification key is presented.
PMID- 29335871
TI - Validation of tautomeric and protomeric binding modes by free energy
calculations. A case study for the structure based optimization of D-amino acid
oxidase inhibitors.
AB - Optimization of fragment size D-amino acid oxidase (DAAO) inhibitors was
investigated using a combination of computational and experimental methods.
Retrospective free energy perturbation (FEP) calculations were performed for
benzo[d]isoxazole derivatives, a series of known inhibitors with two potential
binding modes derived from X-ray structures of other DAAO inhibitors. The good
agreement between experimental and computed binding free energies in only one of
the hypothesized binding modes strongly support this bioactive conformation.
Then, a series of 1-H-indazol-3-ol derivatives formerly not described as DAAO
inhibitors was investigated. Binding geometries could be reliably identified by
structural similarity to benzo[d]isoxazole and other well characterized series
and FEP calculations were performed for several tautomers of the deprotonated and
protonated compounds since all these forms are potentially present owing to the
experimental pKa values of representative compounds in the series. Deprotonated
compounds are proposed to be the most important bound species owing to the
significantly better agreement between their calculated and measured affinities
compared to the protonated forms. FEP calculations were also used for the
prediction of the affinities of compounds not previously tested as DAAO
inhibitors and for a comparative structure-activity relationship study of the
benzo[d]isoxazole and indazole series. Selected indazole derivatives were
synthesized and their measured binding affinity towards DAAO was in good
agreement with FEP predictions.
PMID- 29335872
TI - Disruptor of telomeric silencing 1-like (DOT1L): disclosing a new class of non
nucleoside inhibitors by means of ligand-based and structure-based approaches.
AB - Chemical inhibition of chromatin-mediated signaling involved proteins is an
established strategy to drive expression networks and alter disease progression.
Protein methyltransferases are among the most studied proteins in epigenetics
and, in particular, disruptor of telomeric silencing 1-like (DOT1L) lysine
methyltransferase plays a key role in MLL-rearranged acute leukemia Selective
inhibition of DOT1L is an established attractive strategy to breakdown aberrant
H3K79 methylation and thus overexpression of leukemia genes, and leukemogenesis.
Although numerous DOT1L inhibitors have been several structural data published no
pronounced computational efforts have been yet reported. In these studies a first
tentative of multi-stage and LB/SB combined approach is reported in order to
maximize the use of available data. Using co-crystallized ligand/DOT1L complexes,
predictive 3-D QSAR and COMBINE models were built through a python implementation
of previously reported methodologies. The models, validated by either modeled or
experimental external test sets, proved to have good predictive abilities. The
application of these models to an internal library led to the selection of two
unreported compounds that were found able to inhibit DOT1L at micromolar level.
To the best of our knowledge this is the first report of quantitative LB and SB
DOT1L inhibitors models and their application to disclose new potential
epigenetic modulators.
PMID- 29335873
TI - Agricultural non-point source pollution management in a reservoir watershed based
on ecological network analysis of soil nitrogen cycling.
AB - The Miyun Reservoir plays a pivotal role in providing drinking water for the city
of Beijing. In this research, ecological network analysis and scenario analysis
were integrated to explore soil nitrogen cycling of chestnut and Chinese pine
forests in the upper basin of the Miyun Reservoir, as well as to seek favorable
fertilization modes to reduce agricultural non-point source pollution. Ecological
network analysis results showed that (1) the turnover time was 0.04 to 0.37 year
in the NH4+ compartment and were 15.78 to 138.36 years in the organic N
compartment; (2) the Finn cycling index and the ratio of indirect to direct flow
were 0.73 and 11.92 for the chestnut forest model, respectively. Those of the
Chinese pine forest model were 0.88 and 29.23, respectively; and (3) in the
chestnut forest model, NO3- accounted for 96% of the total soil nitrogen loss,
followed by plant N (2%), NH4+ (1%), and organic N (1%). In the Chinese pine
forest, NH4+ accounted for 56% of the total soil nitrogen loss, followed by
organic N (34%) and NO3- (10%). Fertilization mode was identified as the main
factor affecting soil N export. To minimize NH4+ and NO3- outputs while
maintaining the current plant yield (i.e., 7.85e0 kg N/year), a fertilization
mode of 162.50 kg N/year offered by manure should be adopted. Whereas, to achieve
a maximum plant yield (i.e., 3.35e1 kg N/year) while reducing NH4+ and NO3-
outputs, a fertilization mode of 325.00 kg N/year offered by manure should be
utilized. This research is of wide suitability to support agricultural non-point
source pollution management at the watershed scale.
PMID- 29335874
TI - Mass balance of arsenic fluxes in rivers impacted by gold mining activities in
Paracatu (Minas Gerais State, Brazil).
AB - Arsenic (As) is a dangerous and carcinogenic element and drinking water is its
main pathway of human exposure. Gold mines are widely recognized as important
sources of As pollution. This work proposes the assessment of As distribution
along watersheds surrounding "Morro do Ouro" gold mine (Paracatu, southeastern
Brazil). A balance approach between filtered As fluxes (As < 0.45 MUm) and
suspended particulate material (AsSPM) in different river segments was applied.
Ultrafiltration procedure was used to categorize As into the following classes:
particulate > 0.1 MUm, colloidal < 0.1 MUm to > 10 kDa, dissolved < 10 kDa to > 1
kDa, and truly dissolved < 1 kDa. By applying this approach, arsenic
contributions from mining facilities were quantified in order to identify
critical fluvial segments and support decision makers in actions of remediation.
The mass balance indicated the occurrence of a decreasing gradient from upstream
to downstream: (i) of the As concentrations higher than the limit established by
Brazilian law (10 MUg L-1); (ii) of the ratio between specific fluxes (g As km-2
day-1) and those determined using an uncontaminated watershed (a proxy for
estimating the anthropic contribution), from 103 to 101; (iii) of the specific
fluxes As < 0.45 MUm and AsSPM from 102 to 100; and (iv) of the negative balance
output minus input for each river segment that suggests As accumulation in
sediments along the rivers in both urban and rural areas, mainly due to SPM
sedimentation and sorption by Fe oxyhydroxides. Ultrafiltration shattering showed
concentrations of decreasing As with particle size; the SPM load (> 0.1 MUm) was
almost one order higher to dissolved load (< 1 kDa).
PMID- 29335875
TI - Seasonal variation and source apportionment of PM2.5-bound trace elements at a
coastal area in southwestern Taiwan.
AB - The aim of this study is to investigate the seasonal variations and source
apportionment on atmospheric fine particulate matter (PM2.5) mass and associated
trace element concentrations at a coastal area, in Chiayi County of southwestern
Taiwan. Particle measurements were conducted in 2015. Twenty-three trace elements
in PM2.5 were analyzed using inductively coupled plasma mass spectrometry (ICP
MS). Multiple approaches of the enrichment factor (EF) analysis and positive
matrix fraction (PMF) model were used to identify potential sources of PM2.5
bound trace elements. Daily mean concentration of PM2.5 in cold season (25.41 MUg
m-3) was higher than that in hot season (13.10 MUg m-3). The trace elements
contributed 11.02 and 10.74% in total PM2.5 mass concentrations in cold season
and hot season, respectively. The results of EF analysis confirmed that Sb, Mo,
and Cd were the top three anthropogenic trace elements in the PM2.5; furthermore,
carcinogenic elements (Cr, Ni, and As) and other trace elements (Na, K, V, Cu,
Zn, Sr, Sn, Ba, and Pb) were attributable to anthropogenic emissions in both cold
and hot seasons; however, highly enriched Li and Mn were observed only in cold
season. The PMF model identified four main sources: iron and steel industry, soil
and road dust, coal combustion, and traffic-related emission. Each of these
sources has an annual mean contribution of 8.2, 27.5, 11.2, and 53.1%,
respectively, to PM2.5. The relative dominance of each identified source varies
with changing seasons. The highest contributions occurred in cold season for iron
and steel industry (66.2%), in hot season for traffic-related emission (58.4%),
soil and road dust (22.0%), and coal combustion (2.8%). These findings revealed
that the PM2.5 mass concentration, PM2.5-bound trace element concentrations, and
their contributions were various by seasons.
PMID- 29335876
TI - Hydrogen metabolic patterns driven by Clostridium-Streptococcus community shifts
in a continuous stirred tank reactor.
AB - The hydrogen (H2) production efficiency in dark fermentation systems is strongly
dependent on the occurrence of metabolic pathways derived from the selection of
microbial species that either consume molecular H2 or outcompete hydrogenogenic
bacteria for the organic substrate. In this study, the effect of organic loading
rate (OLR) on the H2 production performance, the metabolic pathways, and the
microbial community composition in a continuous system was evaluated. Two
bacterial genera, Clostridium and Streptococcus, were dominant in the microbial
community depending on the OLR applied. At low OLR (14.7-44.1 gLactose/L-d),
Clostridium sp. was dominant and directed the system towards the acetate-butyrate
fermentation pathway, with a maximum H2 yield of 2.14 molH2/molHexose obtained at
29.4 gLactose/L-d. Under such conditions, the volumetric hydrogen production rate
(VHPR) was between 3.2 and 11.6 LH2/L-d. In contrast, relatively high OLR (58.8
and 88.2 gLactose/L-d) favored the dominance of Streptococcus sp. as co-dominant
microorganism leading to lactate production. Under these conditions, the formate
production was also stimulated serving as a strategy to dispose the surplus of
reduced molecules (e.g., NADH2+), which theoretically consumed up to 5.72 LH2/L
d. In such scenario, the VHPR was enhanced (13.7-14.5 LH2/L-d) but the H2 yield
dropped to a minimum of 0.74 molH2/molHexose at OLR = 58.8 gLactose/L-d. Overall,
this research brings clear evidence of the intrinsic occurrence of metabolic
pathways detrimental for biohydrogen production, i.e., lactic acid fermentation
and formate production, suggesting the use of low OLR as a strategy to control
them.
PMID- 29335877
TI - Development of cyclic AMP receptor protein-based artificial transcription factor
for intensifying gene expression.
AB - Vector-dependent gene overexpression typically relies on an efficient operon and
sufficient RNA polymerases (RNAPs). The lac (lactose) operon is a paradigm of
transcription control, and cyclic AMP receptor protein (CRP) is a global
regulator capable of recruiting RNAPs. However, the gap between lac operon and
CRP has not been well bridged. In this work, CRP was fused to lac repressor
protein (lacI) to form an artificial transcription factor (ATF) with the
expectation that when LacI acted on the lacO-positioned upstream of gene of
interest, the LacI-tethered CRP would trap RNAPs and thus improve the expression
of PuuC, an aldehyde dehydrogenase catalyzing 3-hydroxypropionaldehyde (3-HPA) to
3-hydroxypropionic acid (3-HP) in Klebsiella pneumoniae. As expected, SDS-PAGE
and HPLC showed enhanced PuuC expression and 3-HP production, respectively,
compared to the control strain without expressing chimeric protein LacI-CRP.
Moreover, quantitative real-time PCR demonstrated increased transcription levels
of both PuuC and RNAP coding genes. In shake-flask cultivation, the recombinant
K. pneumoniae strain coexpressing LacI-CRP and PuuC produced 1.67-fold of 3-HP
relative to the stain only overexpressing PuuC. In bioreactor cultivation, the
strain coexpressing LacI-CRP and PuuC produced 35.1 g/L 3-HP, whereas the strain
without expressing LacI-CRP generated only 9.8 g/L 3-HP. Overall, these results
indicated that as an ATF, LacI-CRP significantly boosted PuuC expression and 3-HP
production. We envision that LacI-CRP as a plug-and-play part can be used for
regulating gene expression.
PMID- 29335878
TI - Antioxidant Compounds Recovery from Jucara Residue by Thermal Assisted
Extraction.
AB - This study aimed to recover bioactive compounds by solid-liquid extraction from
the agro-industrial residue obtained during jucara fruits processing into pulp. A
preliminary study using different solvents (methanol, ethanol and water)
indicated ethanol in aqueous solution as the best solvent for antioxidants
recovery. Then, a Box-Behnken design was applied considering as independent
variables the solvent composition (30-70% ethanol in water), temperature (30-70
degrees C) and time (30-60 min), in order to evaluate the effects of these
factors on antioxidant activity in jucara extract. Results showed that the
extracts with higher antioxidant activity were obtained using 30% ethanol at 70
degrees C for 60 min; measurements included ABTS and DPPH assays, determination
of total phenolic content and total monomeric anthocyanins. Furthermore, the
effect of pH in antioxidants recovery was evaluated. For this purpose, the 30%
ethanol solution was acidified to pH 1 and 2 with HCl. Principal component
analysis showed the formation of three distinct groups: one characterized by high
bioactive compounds content (pH 1.0), another with superior antioxidant activity
(pH 5.75, non-acidified), and finally the group at pH 2 presenting the worst
concentrations in the evaluated responses. HPLC analysis showed the presence of
cyanidin-3-O-rutinoside and cyanidin-3-O-glucoside in the extracts. Therefore,
the conventional solid-liquid extraction using renewable solvent can be
successfully applied to recover bioactive compounds from jucara residue, which
can be used by different food industries.
PMID- 29335879
TI - Current Approaches and New Developments in the Pharmacological Management of
Tourette Syndrome.
AB - Tourette syndrome (TS) is a neurodevelopmental disorder of unknown etiology
characterized by spontaneous, involuntary movements and vocalizations called
tics. Once thought to be rare, TS affects 0.3-1% of the population. Tics can
cause physical discomfort, emotional distress, social difficulties, and can
interfere with education and desired activities. The pharmacologic treatment of
TS is particularly challenging, as currently the genetics, neurophysiology, and
neuropathology of this disorder are still largely unknown. However, clinical
experience gained from treating TS has helped us better understand its
pathogenesis and, as a result, derive treatment options. The strongest data exist
for the antipsychotic agents, both typical and atypical, although their use is
often limited in children and adolescents due to their side-effect profiles.
There are agents in a variety of other pharmacologic categories that have
evidence for the treatment of TS and whose side-effect profiles are more
tolerable than the antipsychotics; these include clonidine, guanfacine, baclofen,
topiramate, botulinum toxin A, tetrabenazine, and deutetrabenazine. A number of
new agents are being developed and tested as potential treatments for TS. These
include valbenazine, delta-9-tetrahydrocannabidiol, and ecopipam. Additionally,
there are agents with insufficient data for efficacy, as well as agents that have
been shown to be ineffective. Those without sufficient data for efficacy include
clonazepam, ningdong granule, 5-ling granule, omega-3 fatty acids, and n
acetylcysteine. The agents that have been shown to be ineffective include
pramipexole and metoclopramide. We will review all of the established
pharmacologic treatments, and discuss those presently in development.
PMID- 29335881
TI - Reply to Reck-Burneo et al.: imaging anorectal and cloacal malformations.
PMID- 29335883
TI - ?
PMID- 29335882
TI - Clinical response to Vim's thalamic stereotactic radiosurgery for essential
tremor is associated with distinctive functional connectivity patterns.
AB - INTRODUCTION: Essential tremor (ET) is the most common movement disorder. Drug
resistant ET can benefit from standard surgical stereotactic procedures (deep
brain stimulation, thalamotomy) or minimally invasive high-intensity focused
ultrasound (HIFU) or stereotactic radiosurgical thalamotomy (SRS-T). Resting
state fMRI (rs-fMRI) is a non-invasive imaging method acquired in absence of a
task. We examined whether rs-fMRI correlates with tremor score on the treated
hand (TSTH) improvement 1 year after SRS-T. METHODS: We included 17 consecutive
patients treated with left unilateral SRS-T in Marseille, France. Tremor score
evaluation and rs-fMRI were acquired at baseline and 1 year after SRS-T. Resting
state data (34 scans) were analyzed without a priori hypothesis, in Lausanne,
Switzerland. Based on degree of improvement in TSTH, to consider SRS-T at least
as effective as medication, we separated two groups: 1, <= 50% (n = 6, 35.3%); 2,
> 50% (n = 11, 64.7%). They did not differ statistically by age (p = 0.86),
duration of symptoms (p = 0.41), or lesion volume at 1 year (p = 0.06). RESULTS:
We report TSTH improvement correlated with interconnectivity strength between
salience network with the left claustrum and putamen, as well as between
bilateral motor cortices, frontal eye fields and left cerebellum lobule VI with
right visual association area (the former also with lesion volume). Longitudinal
changes showed additional associations in interconnectivity strength between
right dorsal attention network with ventro-lateral prefrontal cortex and a
reminiscent salience network with fusiform gyrus. CONCLUSIONS: Brain connectivity
measured by resting-state fMRI relates to clinical response after SRS-T. Relevant
networks are visual, motor, and attention. Interconnectivity between visual and
motor areas is a novel finding, revealing implication in movement sensory
guidance.
PMID- 29335880
TI - The long-term effect of erythropoiesis stimulating agents given to preterm
infants: a proton magnetic resonance spectroscopy study on neurometabolites in
early childhood.
AB - BACKGROUND: Erythropoiesis stimulating agents (ESAs) are neuroprotective in cell
and animal models of preterm birth. Prematurity has been shown to alter
neurometabolite levels in children in studies using proton magnetic resonance
spectroscopy (1H-MRS). OBJECTIVE: We hypothesized that ESA treatment in premature
infants would tend to normalize neurometabolites by 4-6 years of age. MATERIALS
AND METHODS: Children in a longitudinal study of neurodevelopment underwent MRI
and 1H-MRS at approximately 4 years and 6 years of age. Prematurely born children
(500-1,250 g birth weight) received ESAs (erythropoietin or darbepoetin) or
placebo during their neonatal hospitalization, and these groups were compared to
healthy term controls. 1H-MRS spectra were obtained from the anterior cingulate
(gray matter) and frontal lobe white matter, assessing combined N-acetylaspartate
and N-acetylaspartylglutamate (tNAA), myo-inositol, choline compounds (Cho),
combined creatine and phosphocreatine, and combined glutamate and glutamine.
RESULTS: No significant (P<=0.5) group differences were observed for any
metabolite level. Significant age-related increases in white-matter tNAA and Cho
were observed, as well as a trend for increased gray-matter tNAA. CONCLUSION:
Neither prematurity nor neonatal ESA treatment was associated with differences in
brain metabolite levels in the children of this study at a significance level of
0.05. These findings suggest that earlier differences that might have existed had
normalized by 4-6 years of age or were too small to be statistically significant
in the current sample.
PMID- 29335884
TI - Effects of moderate exercise on biochemical, morphological, and physiological
parameters of the pancreas of female mice with estrogen deprivation and
dyslipidemia.
AB - Menopausal women are at high risk of developing heart disease. However, physical
exercise practice can reverse this scenario. We evaluated the biochemical,
morphological, and physiological effects of moderate aerobic physical exercise on
the pancreas of knockout mice for LDL receptor with estrogen deprivation by
ovariectomy. Animals were divided into six groups (n = 5): sedentary non
ovariectomized control; sedentary ovariectomized control; trained ovariectomized
control; sedentary non-ovariectomized LDL-R knockout; sedentary ovariectomized
LDL-R knockout; and trained ovariectomized LDL-R knockout. Physical exercise
practice promoted improvement in biometric and biochemical parameters analyzed,
with reduction of visceral adipose tissue and VLDL, triglycerides, total
cholesterol, and blood glucose levels. In addition, physical exercise practice
altered the morphology of pancreatic islets and improved their response to the
effects of menopause. Thus, physical exercise practice was fundamental to
minimize the effects of dyslipidemia associated with ovariectomy in the
pancreatic tissue of LDL-R knockout animals, contributing to reduce the risk of
developing cardiac diseases in the menopause period.
PMID- 29335885
TI - Glottic Foreign Body Removal: A Novel Approach.
PMID- 29335886
TI - Effect of actual age on outcome at discharge in patients by surgical clipping and
endovascular coiling for ruptured cerebral aneurysm in Japan.
AB - The Japanese population features the highest rate of elderly individuals
worldwide. However, the difference of actual age indication for surgical clipping
(SC) and endovascular coiling (EC) has never reported. We clarified the effect of
actual age on poor outcome at discharge in patients by each treatment for
ruptured cerebral aneurysm according to the Japanese Stroke Data Bank. A total of
3593 patients with ruptured saccular cerebral aneurysm were treated by SC and/or
EC between 2000 and 2013. The effect of actual age on poor outcome (modified
Rankin scale [mRS] score > 2) at discharge was evaluated by the cutoff age using
receiver operating characteristic analysis for each treatment. There were 2666
cases in the SC group and 881 cases in the EC group. The cutoff age for poor
outcome was 3 to 9 years older for EC than for SC. The gap of cutoff age between
two treatments was 3 years shorter in mild subarachnoid hemorrhage than severe
cases. The gap of cutoff age between two treatments was 7 years in elderly
patients over 65 years old. The cutoff age was 78 years old for both SC and EC in
elderly female patients. In conclusion, the cutoff age for poor mRS score > 2 was
3 to 9 years older for EC than for SC. Actual age was one of the indications for
elderly patients to achieve the optimum outcome; however, the treatment
indication should be carefully considered based on the condition in each country.
PMID- 29335887
TI - Sphingadienes show therapeutic efficacy in neuroblastoma in vitro and in vivo by
targeting the AKT signaling pathway.
AB - Neuroblastoma is a childhood malignancy that accounts for approximately 15% of
childhood cancer deaths. Only 20-35% of children with metastatic neuroblastoma
survive with standard therapy. Identification of more effective therapies is
essential to improving the outcome of children with high-stage disease.
Sphingadienes (SD) are growth-inhibitory sphingolipids found in natural sources
including soy. They exhibit chemopreventive activity in mouse models of colon
cancer, where they mediate cytotoxicity by inhibiting key pro-carcinogenic
signaling pathways. In this study, the effect of SD on neuroblastoma was
analyzed. Low micromolar concentrations of SD were cytotoxic to transformed and
primary neuroblastoma cells independently of N-Myc amplification status. SD
induced both caspase-dependent apoptosis and autophagy in neuroblastoma cells.
However, only inhibition of caspase-dependent apoptosis protected neuroblastoma
cells from SD-mediated cytotoxicity. SD also inhibited AKT activation in
neuroblastoma cells as shown by reduced phosphorylated AKT levels. Pre-treatment
with insulin attenuated SD-mediated cytotoxicity in vitro. SD-loaded
nanoparticles (NP) administered parenterally to immunodeficient mice carrying
neuroblastoma xenografts resulted in cytotoxic levels of SD in the circulation
and significantly reduced tumor growth compared to vehicle-treated controls.
Analysis of tumor extracts demonstrated reduced AKT activation in tumors of mice
treated with SD-NP compared to controls treated with empty NP. Our findings
indicate SD are novel potential chemotherapeutic agents that promote
neuroblastoma cell death and reduce tumorigenicity in vivo.
PMID- 29335888
TI - Root lengthening with apical closure in two maxillary immature permanent central
incisors after placement of mineral trioxide aggregate (MTA) as an apical plug.
AB - BACKGROUND: Necrosis of permanent immature teeth is a common reason for
consultation in paediatric dentistry. Apexification is a therapeutic procedure
aiming to create an apical calcified barrier in open apex teeth. CASE REPORT: Two
cases are presented in which apexification were completed on immature permanent
traumatised incisors using a mineral trioxide aggregate (MTA) plug. FOLLOW-UP: At
2 and 5 years showed apical closure and radicular elongation beyond the MTA plug.
CONCLUSION: Unexpectedly, a regeneration of mineral tissues beyond the MTA plug
occurred which is an uncommon outcome.
PMID- 29335890
TI - Effectiveness of Sodium-Glucose Cotransporter-2 Inhibitor as an Add-on Drug to
GLP-1 Receptor Agonists for Glycemic Control of a Patient with Prader-Willi
Syndrome: A Case Report.
AB - INTRODUCTION: Diabetes patients with Prader-Willi syndrome (PWS) are obese
because of hyperphagia; weight control by dietary modification and medicine is
required for glycemic control. There are several recent reports showing the
effectiveness of GLP-1 receptor agonists (GLP-1RAs) for diabetes treatment in
PWS. CASE REPORT: A 36-year-old Japanese male patient was diagnosed with PWS at
10 years of age. At age 16 years, he was diagnosed with diabetes and began to
take several kinds of oral hypoglycemic agents. At age 29 years, his BMI was 39.1
kg/m2 and he was referred to our department for diabetes and obesity treatment.
In the present case, the HbA1c was not improved by GLP-1RAs despite a 28-kg BW
reduction, which included a 9-kg loss of muscle. Apprehensive of further loss of
muscle mass, basal insulin of insulin glargine was administered in addition to
GLP-1RAs. Immediately after the addition of tofogliflozin, a sodium-glucose
cotransporter-2 (SGLT2) inhibitor, the patient's HbA1c decreased dramatically
with only about an additional 3% BW reduction. We note an improvement in our case
of lipid deposition in the pancreas confirmed by abdominal CT after the
improvement of HbA1c. It is unknown whether this improvement of fatty pancreas
was a cause or an effect of the improved glycemic control in the present case.
CONCLUSION: This finding clearly supports the effectiveness of combining SGLT2
inhibitors with GLP-1RAs for treatment of patients with PWS and non-alcoholic
fatty pancreas disease.
PMID- 29335889
TI - Comparison of gray matter volume between migraine and "strict-criteria" tension
type headache.
AB - BACKGROUND: Despite evidently distinct symptoms, tension-type headache (TTH) and
migraine are highly comorbid and exhibit many similarities in clinical practice.
The purpose of this study was to investigate whether both types of headaches are
similar in brain morphology. METHODS: Consecutive patients with TTH and age- and
sex-matched patients with migraine and healthy controls were enrolled for brain
magnetic resonance imaging examination. Patients with TTH were excluded if they
reported any headache features or associated symptoms of migraine. Changes in
gray matter (GM) volume associated with headache diagnosis (TTH vs. migraine) and
frequency (episodic vs. chronic) were examined using voxel-based morphometry. The
correlation with headache profile and the discriminative ability between TTH and
migraine were also investigated for these GM changes. RESULTS: In comparison with
controls (n = 43), the patients with TTH (25 episodic and 24 chronic) exhibited a
GM volume increase in the anterior cingulate cortex, supramarginal gyrus,
temporal pole, lateral occipital cortex, and caudate. The patients with migraine
(31 episodic and 25 chronic) conversely exhibited a GM volume decrease in the
orbitofrontal cortex. These GM changes did not correlate with any headache
profile. A voxel-wise 2 * 2 factorial analysis further revealed the substantial
effects of headache types and frequency in the comparison of GM volume between
TTH and migraine. Specifically, the migraine group (vs. TTH) had a GM decrease in
the superior and middle frontal gyri, cerebellum, dorsal striatum, and precuneus.
The chronic group (vs. episodic group) otherwise demonstrated a GM decrease in
the bilateral insula and anterior cingulate cortex. In receiver operating
characteristic analysis, the GM volumes of the left superior frontal gyrus and
right cerebellum V combined had good discriminative ability for distinguishing
TTH and migraine (area under the curve = 0.806). CONCLUSIONS: TTH and migraine
are separate headache disorders with different characteristics in relation to GM
changes. The major morphological difference between the two types of headaches is
the relative GM decrease of the prefrontal and cerebellar regions in migraine,
which may reflect a higher allostatic load associated with this disabling
headache.
PMID- 29335891
TI - Serum Bilirubin Concentration is Associated with Left Ventricular Remodeling in
Patients with Type 2 Diabetes Mellitus: A Cohort Study.
AB - INTRODUCTION: Previous studies have shown that serum bilirubin concentration is
inversely associated with the risk of cardiovascular disease. The relationship
between serum bilirubin concentration and left ventricular geometry, however, has
not been investigated in patients with diabetes mellitus. METHODS: In this cohort
study, 158 asymptomatic patients with type 2 diabetes mellitus without overt
heart disease were enrolled. Left ventricular structure and function were
assessed using echocardiography. Serum bilirubin concentration, glycemic control,
lipid profile, and other clinical characteristics were evaluated, and their
association with left ventricular geometry was determined. Patients with New York
Heart Association Functional Classification greater than I, left ventricular
ejection fraction less than 50%, history of coronary artery disease, severe
valvulopathy, chronic atrial fibrillation, or creatinine clearance less than 30
ml/min, and those receiving insulin treatment, were excluded. RESULTS: Univariate
analyses showed that relative wall thickness (RWT) was significantly correlated
with diastolic blood pressure (P = 0.003), HbA1c (P = 0.024), total cholesterol
(P = 0.043), urinary albumin (P = 0.023), and serum bilirubin concentration (P =
0.009). There was no association between left ventricular mass index and serum
bilirubin concentration. Multivariate linear regression analysis showed that log
RWT was positively correlated with diastolic blood pressure (P = 0.010) and that
log RWT was inversely correlated with log bilirubin (P = 0.003). In addition, the
patients with bilirubin less than 0.8 mg/dl had a higher prevalence of concentric
left ventricular remodeling compared with those with bilirubin 0.8 mg/dl or more.
CONCLUSION: Our study shows that the serum bilirubin concentration may be
associated with the progression of concentric left ventricular remodeling in
patients with type 2 diabetes mellitus.
PMID- 29335892
TI - Is sugammadex alone sufficient to cause anaphylaxis?
PMID- 29335893
TI - Neurological prognosis of 6 cases after chest compression during general
anesthesia.
AB - INTRODUCTION: Data on the outcomes after chest compression (CC) of patients who
are under general anesthesia (GA) are limited. The present study aimed to
evaluate the neurological outcomes in patients who received CC while under GA.
METHODS: The patients who received CC while under GA, between 2010 and 2015, in
Kyoto Medical Center were surveyed retrospectively. The primary outcome was poor
neurologic function or death, as defined by a cerebral performance category score
(CPC) score of 3-5 on day 28. RESULTS: Six patients received CC while under GA,
and four patients had poor neurological outcomes with a CPC score of 4 or 5 on
day 28. All these patients required emergency operation because of their primary
disease. CONCLUSION: Even if the patients were monitored and immediately managed
under GA, ineffective management of preoperative conditions tended to result in
the poor neurological prognosis.
PMID- 29335894
TI - Management of periprosthetic shoulder infections with the use of a permanent
articulating antibiotic spacer.
AB - INTRODUCTION: Management of periprosthetic shoulder infections (PSIs) still
remains challenging. We conducted a retrospective case study to assess the
outcomes of definitive articulating antibiotic spacer implantation in a cohort of
elderly, low-demanding patients. We hypothesized that in patients with low
functional demands seeking pain relief with chronic PSIs, treatment with a
definitive articulating antibiotic spacer would lead to satisfying results
concerning eradication of the infection, improvement of pain, and improving
shoulder function. MATERIALS AND METHODS: 19 patients underwent definitive
articulating antibiotic spacer implantation for the treatment of an infected
shoulder arthroplasty. Mean age at surgery was 70.2 years. Patients were assessed
pre-operatively with functional assessment including Constant-Murley score, and
objective examination comprehending ROM, visual analog scale pain score, and
patient subjective satisfaction (excellent, good, satisfied, or unsatisfied)
score. Radiographs were taken to examine signs of loosening, and change in
implant positioning. RESULTS: At the most recent follow-up, none of the patients
had clinical or radiographic signs suggesting recurrent infection. Most patients
reported satisfying subjective and objective outcomes. Follow-up examination
showed significant improvement of all variables compared to pre-operative values
(p < 0.001). Radiographs did not show progressive radiolucent lines or change in
the position of the functional spacer. In one case, glenoid osteolysis was
reported, which did not affect the clinical outcome. CONCLUSIONS: In selected
elderly patients with low functional demands seeking pain relief with infected
shoulder arthroplasty, definitive management with a cement spacer is a viable
treatment option that helps in eradicating shoulder infection and brings
satisfying subjective and objective outcomes. LEVEL OF EVIDENCE: Case series,
Level IV.
PMID- 29335895
TI - Pharmacokinetics, Antiviral Activity, and Safety of Rilpivirine in Pregnant Women
with HIV-1 Infection: Results of a Phase 3b, Multicenter, Open-Label Study.
AB - INTRODUCTION: Physiologic changes during pregnancy may impact the
pharmacokinetics of drugs. In addition, efficacy and safety/tolerability concerns
have been identified for some antiretroviral agents. METHODS: Human
immunodeficiency virus (HIV)-1-infected pregnant women (18-26 weeks gestation)
receiving the non-nucleoside reverse transcriptase inhibitor rilpivirine 25 mg
once daily were enrolled in this phase 3b, open-label study examining the impact
of pregnancy on the pharmacokinetics of rilpivirine when it is given in
combination with other antiretroviral agents. Blood samples (collected over the
24-h dosing interval) to assess total and unbound rilpivirine plasma
concentrations were obtained during the second and third trimesters (24-28 and 34
38 weeks gestation, respectively) and 6-12 weeks postpartum. Pharmacokinetic
parameters were derived using noncompartmental analysis and compared (pregnancy
versus postpartum) using linear mixed effects modeling. Antiviral and immunologic
response and safety were assessed. RESULTS: Nineteen women were enrolled; 15 had
evaluable pharmacokinetic results. Total rilpivirine exposure was 29-31% lower
during pregnancy versus postpartum; differences were less pronounced for unbound
(pharmacodynamically active) rilpivirine. At study entry, 12/19 (63.2%) women
were virologically suppressed; 10/12 (83.3%) women were suppressed at the
postpartum visit. Twelve infants were born to the 12 women who completed the
study (7 discontinued); no perinatal viral transmission was observed among 10
infants with available data. Rilpivirine was generally safe and well tolerated in
women and infants exposed in utero. CONCLUSION: Despite decreased rilpivirine
exposure during pregnancy, treatment was effective in preventing mother-to-child
transmission and suppressing HIV-1 RNA in pregnant women. Results suggest that
rilpivirine 25 mg once daily, as part of individualized combination
antiretroviral therapy, may be an appropriate option for HIV-1-infected pregnant
women. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT00855335.
PMID- 29335896
TI - Familial occurrence of gastroschisis: a population-based overview on recurrence
risk, sex-dependent influence, and geographical distribution.
AB - PURPOSE: There is uncertainty over whether familial recurrences in gastroschisis
might be higher. Moreover, scant information is available regarding its
sociodemographic features. We aim to explore the recurrence risk, sex-dependent
influence, and geographical distribution of familial gastroschisis. METHODS: A
systematic review of the literature and data extraction from population-based
studies published 1970-2017 (PubMed/MEDLINE) was independently performed by two
reviewers. Familial ocurrence of gastroschisis, whereas sociodemographic features
from 11 studies were pooled including 862 probands as a base. A descriptive
analysis and Chi-square test were performed. RESULTS: Twenty-four probands had a
positive family history of gastroschisis including 49 affected family members,
for a recurrence risk of 5.7 and 3% adjusted for proband. Siblings' recurrence
was 4.3%. Sex-dependent influence analysis (n = 879, from three studies)
evidenced an increased susceptibility to gastroschisis in males (2.5%) compared
to females (1.3%) adjusted for proband. Heterogeneity was identified by Fisher's
exact test (P = 0.023). CONCLUSION: Our findings support a greater liability
attributable to familial factors on gastroschisis along with significant
information for family and prenatal counseling. We suggest that future studies
should include for a more accurate account for both familial and environmental
confounding factors to uncover relatives and environmental exposures that more
limited family histories may have missed.
PMID- 29335897
TI - Splenectomy in systemic lupus erythematosus and autoimmune hematologic disease: a
comparative analysis.
AB - : The objective of the study is to analyze the efficacy and safety of splenectomy
in the management of refractory autoimmune thrombocytopenia (AT)/autoimmune
hemolytic anemia (AIHA) associated or not with systemic lupus erythematosus.
Thirty-four patients after splenectomy due to severe AT and/or AIHA were divided
into group 1 (G1) 18 SLE/APS patients: 9 AT/SLE patients, 6 SLE/antiphospholipid
syndrome (APS), and 3 primary APS. Group 2 (G2): 16 patients without SLE/APS: 2
Fisher-Evans syndrome and 14 AIHA. Surgery approach when (1) platelets <=
50,000/ml despite 2 weeks on medical therapy, (2) medically dependent, and (3)
medically intolerant or after two hemolytic crises in AIHA patients. Splenectomy
response: (1) complete (CR): >= 150,000 platelets/ml, (2) partial: 50,000
149,000/ml, or (3) none: <= 50,000/ml. CR for AIHA: hemoglobin >=9 g/dl.
STATISTICAL ANALYSIS: descriptive statistics and chi-square test. The mean age
was 34.6 years; mean follow-up: 28.5 months. Open splenectomy in 15/34 vs
laparoscopy in 19/34 (p = NS). CR in 15/34, G1: 4/18, G2: 11/16, (p = 0.006).
Complications in 6/34, 5 from G2 vs 1 from G1 (p = 0.05). Relapse in 7/18
patients in G1 and 3/16 in G2 (p = 0.05). Open and laparoscopic splenectomies in
SLE and AT patients are as effective as in those without SLE; however, patients
with SLE and APS had more relapses.
PMID- 29335898
TI - The novel transcription factor TRP interacts with ZFP5, a trichome initiation
related transcription factor, and negatively regulates trichome initiation
through gibberellic acid signaling.
AB - KEY MESSAGE: The trichome-related protein (TRP) is a novel transcription factor
(TF) that negatively regulates trichome initiation-related TFs through
gibberellin (GA) signaling. Trichomes, which are outgrowths of leaf epidermal
cells, provide the plant with a first line of defense against damage from
herbivores and reduce transpiration. The initiation and development of trichomes
are regulated by a network of positively or negatively regulating transcription
factors (TFs). However, little information is currently available on
transcriptional regulation related to trichome formation. Here, we report a novel
TF Trichome-Related Protein (TRP) that was observed to negatively regulate the
trichome initiation-related TFs through gibberellic acid (GA) signaling.
ProTRP:GUS revealed that TRP was only expressed in the trichome. The TRP loss-of
function mutant (trp) had an increased number of trichomes on the flower, cauline
leaves, and main inflorescence stems compared to the wild-type. In contrast, TRP
overexpression lines (TRP-Ox) exhibited a decreased number of trichomes on
cauline leaves and main inflorescence stem following treatment with exogenous GA.
Moreover, the expressions of trichome initiation regulators (GIS, GIS2, ZFP8,
GL1, and GL3) increased in trp plants but decreased in TRP-Ox lines after GA
treatment. TRP was observed to physically interact with ZFP5, a C2H2 TF that
controls trichome cell development through GA signaling, both in vivo and in
vitro. Based on these results, we suggest that TRP functions upstream of the
trichome initiation regulators and represses the binding of ZFP5 to the ZFP8
promoter.
PMID- 29335899
TI - The ultrasonographic "whirlpool sign" in testicular torsion: valuable tool or
waste of valuable time? A systematic review and meta-analysis.
AB - PURPOSE: A positive whirlpool sign (WS) is defined as the presence of a spiral
like pattern when the spermatic cord is assessed during ultrasonography (US),
using standard, high-resolution ultrasonography (HRUS) and/or color Doppler
sonography (CDS), in the presence of testicular torsion. The objective of this
review was to assess the validity and accuracy of this sign by performing a
comprehensive systematic literature review and meta-analysis. METHODS: In
accordance with the Preferred Reporting Items for Systematic Reviews and Meta
analyses (PRISMA) guidelines, a comprehensive literature search was performed
(August, 2017), using the following databases: BMJ Best Practice, Cochrane
Library, Embase, PubMed, Scopus, and Web of Science. Selected studies were
further assessed for relevance and quality using the Oxford 2010 Critical
Appraisal Skills Program (CASP). RESULTS: Of the studies assessed, a total of 723
participants were included, with a mean of 72.3 (SD 71.9) participants. Of the
participants, 226 (31.3%) were diagnosed with testicular torsion (TT). Meta
analysis of the studies that provided sufficient data resulted in a pooled
sensitivity and specificity of the WS of 0.73 (95% CI, 0.65-0.79) and 0.99 (95%
CI, 0.92-0.99), respectively. Removal of all neonates increased the pooled
sensitivity to 0.92 (95% CI, 0.70-0.98) while the pooled specificity remained
almost unchanged at 0.99 (95% CI, 0.95-1.00). The estimated summary effect of all
studies with sufficient data was 4.34 (95% CI, 1.01-7.67; n = 394; p = 0.001). A
large degree of heterogeneity was suggested by an I2 statistic of 88.27% (95% CI,
68.60-98.68%). Removal of neonatal subjects increased the estimated summary
effect to 5.32 (95% CI, 1.59-9.05; n = 375; p = 0.001). CONCLUSION: The WS, when
correctly diagnosed, may be viewed as a very definitive sign for TT in the
pediatric and adult populations. However, its role in neonates is limited.
PMID- 29335900
TI - Hypercomplex pedicle subtraction osteotomies: definition, early clinical and
radiological results and complications.
AB - PURPOSE: To describe hypercomplex pedicle subtraction osteotomies (HyC-PSO) for
adult spine deformity with sagittal imbalance in terms of preoperative,
intraoperative and postoperative outcomes and complications. METHODS: From a
prospective single centre database, patients undergoing PSO between January 2016
and May 2017 were reviewed. HyC-PSO were defined as those in patients with one of
the following conditions: sagittal correction > 45 degrees needed at a single
level or at 1-3 consecutive vertebrae, more than 60 degrees of total sagittal
correction needed and PSO on segments of the spine with congenital deformities.
RESULTS: 22 patients were included, 14 had standard PSO (group A) and 8 had HyC
PSO (group B). Significant correction of lumbar lordosis (LL) and pelvic (PT) was
noted in both groups (p < 0.01). Operative time was longer in HyC-PSO, 604 min
compared to standard PSO, 478 min. A trend versus greater intraoperative blood
loss (3837 vs 2285 ml) and greater intraoperative blood infusion (from cell saver
plus homologous, 2306 vs 1280 ml) was recorded in HyC-PSO (ns). Patients in group
B received significantly more blood units intra and postoperatively (8.25 vs 4.71
units, p = 0.006). Sagittal correction at the PSO level (54.7 degrees -30 degrees
to 85 degrees -vs 26.8 degrees -8 degrees to 39 degrees -, p = 0.000) and total
sagittal correction (64.5 degrees -50 to 95 degrees -vs 39.8 degrees -20 degrees
to 51 degrees -, p = 0.000) were greater in HyC-PSO. PROMs at the last available
follow-up did not show significant differences between groups for any of the
outcomes analyzed. Complications were similar in both groups. CONCLUSION: This is
the first report on hypercomplex pedicle subtraction osteotomies. Hypercomplex
PSO describes a subset of clinical scenarios with increased surgical effort that
can be measured as longer surgical time and greater blood transfusion
requirements. Successful correction of misalignment can be achieved in this
specific group of patients, and clinical results and complications profile could
be similar to standard PSO procedures.
PMID- 29335901
TI - Letter to the Editor concerning "Spinal movement and dural sac compression during
airway management in a cadaveric model with atlanto-occipital instability" by
Liao S, Schneider NRE, Weilbacher F, et al. (2017) Eur Spine J;
doi:10.1007/s00586-017-5416-9.
PMID- 29335902
TI - Letter to the Editor concerning "Clinical and radiological factors related to the
presence of motor deficit in lumbar disc prolapse: a prospective analysis of 70
consecutive cases with neurological deficit" by V. Krishnan et al. [Eur Spine J
(2017) 26:2642-2649).
PMID- 29335903
TI - Anterior cervical corpectomy and fusion versus posterior laminoplasty for the
treatment of oppressive myelopathy owing to cervical ossification of posterior
longitudinal ligament: a meta-analysis.
AB - PURPOSE: The purpose of this research is to compare the clinical efficacy,
postoperative complication and surgical trauma between anterior cervical
corpectomy and fusion versus posterior laminoplasty for the treatment of
oppressive myelopathy owing to cervical ossification of the posterior
longitudinal ligament (OPLL). STUDY DESIGN: Systematic review and meta-analysis.
METHODS: An comprehensive search of literature was implemented in three
electronic databases (Embase, Pubmed, and the Cochrane library). Randomized or
non-randomized controlled studies published since January 1990 to July 2017 that
compared anterior cervical corpectomy and fusion (ACCF) versus posterior
laminoplasty (LAMP) for the treatment of cervical oppressive myelopathy owing to
OPLL were acquired. Exclusion criteria were non-human studies, non-controlled
studies, combined anterior and posterior operative approach, the other anterior
or posterior approaches involving cervical discectomy and fusion and laminectomy
with (or without) instrumented fusion, revision surgeries, and cervical
myelopathy caused by cervical spondylotic myelopathy. The quality of the included
articles was evaluated according to GRADE. The main outcome measures included:
preoperative and postoperative Japanese Orthopedic Association (JOA) score; neuro
functional recovery rate; complication rate; reoperation rate; preoperative and
postoperative C2-C7 Cobb angle; operation time and intraoperative blood loss; and
subgroup analysis was performed according to the mean preoperative canal
occupying ratio (Subgroup A:the mean preoperative canal occupying ratio < 60%,
and Subgroup B:the mean preoperative canal occupying ratio >= 60%). RESULTS: A
total of 10 studies containing 735 patients were included in this meta-analysis.
And all of the selected studies were non-randomized controlled trials with
relatively low quality as assessed by GRADE. The results revealed that there was
no obvious statistical difference in preoperative JOA score between the ACCF and
LAMP groups in both subgroups. Also, in subgroup A (the mean preoperative canal
occupying ratio < 60%), no obvious statistical difference was observed in the
postoperative JOA score and neurofunctional recovery rate between the ACCF and
LAMP groups. But, in subgroup B (the mean preoperative canal occupying ratio >=
60%), the ACCF group illustrated obviously higher postoperative JOA score and
neurofunctional recovery rate than the LAMP group (P < 0.01, WMD 1.89 [1.50,
2.28] and P < 0.01, WMD 24.40 [20.10, 28.70], respectively). Moreover, the
incidence of both complication and reoperation was markedly higher in the ACCF
group compared with LAMP group (P < 0.05, OR 1.76 [1.05, 2.97] and P < 0.05, OR
4.63 [1.86, 11.52], respectively). In addition, the preoperative cervical C2-C7
Cobb angle was obviously larger in the LAMP group compared with ACCF group (P <
0.05, WMD - 5.77 [- 9.70, - 1.84]). But no statistically obvious difference was
detected in the postoperative cervical C2-C7 Cobb angle between the two groups.
Furthermore, the ACCF group showed significantly more operation time as well as
blood loss compared with LAMP group (P < 0.01, WMD 111.43 [40.32,182.54], and P <
0.01, WMD 111.32 [61.22, 161.42], respectively). CONCLUSION: In summary, when the
preoperative canal occupying ratio < 60%, no palpable difference was tested in
postoperative JOA score and neurofunctional recovery rate. But, when the
preoperative canal occupying ratio >= 60% ACCF was associated with better
postoperative JOA score and the recovery rate of neurological function compared
with LAMP. Synchronously, ACCF in the cure for cervical myelopathy owing to OPLL
led to more surgical trauma and more incidence of complication and reoperation.
On the other hand, LAMP had gone a diminished postoperative C2-C7 Cobb angle,
that might be a cause of relatively higher incidence of postoperative late
neurofunctional deterioration. In brief, when the preoperative canal occupying
ratio < 60%, LAMP seems to be effective and safe. However, when the preoperative
canal occupying ratio >= 60%, we prefer to choose ACCF while complications could
be controlled by careful manipulation and advanced surgical techniques. No matter
which option you choose, benefits and risks ought to be balanced.
PMID- 29335904
TI - The SAFE pathway for cardioprotection: is this a promising target?
AB - The survivor activating factor enhancement (SAFE) pathway was discovered as an
alternative intrinsic pro-survival signaling pathway to the reperfusion injury
salvage kinase pathway for cardioprotection against ischemia-reperfusion injury.
The delineation of this pathway, made of key components such as cytokines of the
immune system and transcription factors, has brought major advancements in our
understanding on how the heart is able to protect itself against ischemia
reperfusion injury. In this viewpoint, we describe the major steps leading to the
discovery of the SAFE pathway in small animal models to date and we discuss its
translation to large animals and humans.
PMID- 29335905
TI - Influence of antiviral therapy on the liver stiffness in chronic HBV hepatitis.
AB - PURPOSE: The aim of this study was to evaluate the effects of antiviral therapy
on liver stiffness measurement (LSM). METHODS: Two hundred HBV patients were
enrolled from four hospital centers in southern Italy; median age was 50.7 (25
75) males were 68%; 171 patients underwent to liver biopsy and 200 patients had
LSM at baseline and 189 at the end of follow-up. One hundred and forty-nine
patients were treated with nucleos(t)ide analogs, while 51 patients were
untreated. The cutoffs of the LSM, related to the fibrosis stages, were as
follows: non-advanced fibrosis <= 8.1 kPa and advanced fibrosis >= 8.2 Kpa.
RESULTS: At baseline, the median value of LSM was 14.1 kPa for advanced
fibrosis/cirrhosis and 6.9 kPa for non-advanced fibrosis. LSM was performed at 24
months from the start of therapy. The treated patients (68% received Entecavir
and 32% Tenofovir) showed a decrease in liver stiffness measurement of 1.5 kPa (p
< 0.001) in non-advanced fibrosis and of 6 kPa (p < 0.001) in advanced
fibrosis/cirrhosis. In the patients not undergoing antiviral treatment, no
statistically significant change of the LSM was observed (p = 0.26). A logistic
binary regression model showed that the only independent factor associated with a
significant change in the LSM was the liver stiffness value at baseline (odd
ratio 2.855; 95% CI 1.456-5.788; (p = 0.007). CONCLUSION: Long-term antiviral
therapy induced a significant reduction of liver stiffness measurement and this
result may be related to the reduction of liver fibrosis.
PMID- 29335906
TI - The Health Behaviors of Ethnically Diverse Women at Increased Risk of Gestational
Diabetes: The Behaviors Affecting Baby and You (B.A.B.Y.) Study.
AB - Objectives Cigarette smoking, low physical activity, and sedentary behavior are
modifiable risk factors for adverse pregnancy outcomes. However, only one study
has evaluated predictors of these health risk behaviors among women at high risk
for gestational diabetes mellitus (GDM). Therefore, our goal was to examine
predictors of smoking, low physical activity, and sedentary behavior during
pregnancy in an ethnically diverse high risk cohort. Methods This cross-sectional
analysis utilized baseline data from the Behaviors Affecting Baby and You
(B.A.B.Y.) study conducted among prenatal care patients at high risk for GDM
(personal history of GDM or family history of diabetes and body mass index [BMI]
>= 25 kg/m2). Smoking was assessed using questions from the Pregnancy Risk
Assessment Monitoring System questionnaire and sedentary behavior (top vs. lower
quartiles) and moderate/vigorous physical activity (bottom vs. upper quartile)
via the Pregnancy Physical Activity Questionnaire. Results Participants (n = 400)
enrolled at a mean of 12.4 (SD 3.6) weeks gestation. A total of 150 (44.1%)
engaged in one, 37 (10.9%) in two, and 4 (1.2%) in three risk behaviors. Lower
household income and not having children at home were each associated with a 2-6
fold increased odds of smoking, high sedentary behavior, and engaging in at least
one risk behavior. Being married, Hispanic or of younger age was associated with
a 2-6 fold reduced odds of smoking. BMI and personal history of GDM were not
associated with risk behaviors. Conclusions for Practice Findings help
characterize high risk groups and inform prenatal interventions targeting these
health risk behaviors.
PMID- 29335907
TI - Content of First Prenatal Visits.
AB - Objective The purpose of this study was to examine the content of the first
prenatal visit within an academic medical center clinic and to compare the topics
discussed to 2014 American College of Obstetrics and Gynecologists guidelines for
the initial prenatal visit. Methods Clinical interactions were audio recorded and
transcribed (n = 30). A content analysis was used to identify topics discussed
during the initial prenatal visit. Topics discussed were then compared to the
2014 ACOG guidelines for adherence. Coded data was queried though the qualitative
software and reviewed for accuracy and content. Results First prenatal visits
included a physician, nurse practitioner, nurse midwife, medical assistant,
medical students, or a combination of these providers. In general, topics that
were covered in most visits and closely adhered to ACOG guidelines included
vitamin supplementation, laboratory testing, flu vaccinations, and cervical
cancer screening. Topics discussed less often included many components of the
physical examination, education about pregnancy, and screening for an
identification of psychosocial risk. Least number of topics covered included
prenatal screening. Conclusions for Practice While the ACOG guidelines may
include many components that are traditional in addition to those based on
evidence, the guidelines were not closely followed in this study. Identifying new
ways to disseminate information during the time constrained initial prenatal
visit are needed to ensure improved patient outcomes.
PMID- 29335908
TI - Surgery for Abdominal Well-Differentiated Liposarcoma.
AB - OPINION STATEMENT: Retroperitoneal sarcomas are rare tumors of which liposarcoma
is the most common histology. Surgical resection remains the mainstay of therapy,
particularly for the well-differentiated subtype. They can grow to massive size
before causing symptoms or detection. Well-differentiated liposarcoma, while
having a negligible metastatic rate, is fraught with a high local recurrence
rate, despite a complete surgical resection. Reasons for this are not completely
known but may be related to a field defect of the retroperitoneal fat creating a
niche for recurrence. These tumors are classically chemo- and radio-resistant.
Surgical therapy of recurrences can be challenging, but remains the treatment of
choice for well-differentiated liposarcoma. In an attempt to improve on survival
and recurrence rates for retroperitoneal liposarcoma, an extended resection
approach has been promoted by a few groups. This involves the en bloc resection
of contiguous organs that are not macroscopically involved. While this has
improved local recurrence rates, benefit for overall survival has not been
demonstrated. Interestingly, the improvement in local recurrence rate appeared to
be driven by histology and was most improved in the well-differentiated subtype
compared to historical data. However, for well-differentiated liposarcomas that
are multifocal, this approach may be less useful. The application of this
approach still requires further study in terms of balancing increased morbidity
of extended resection against the potential for multiple surgeries for
recurrence.
PMID- 29335909
TI - Persistent posterior seroma after laparoscopic repair of ventral abdominal wall
hernias with expanded polytetrafluoroethylene mesh: prevalence, independent
predictors and detached tacks : Retrospective review.
AB - PURPOSE: A persistent seroma located posterior to a mesh (PPS) remains a little
known complication after laparoscopic ventral hernia repair (LVHR). The aim of
this large case series was to analyse the prevalence and clinical course as well
as identify related factors and independent predictors of PPS. METHODS: All 1288
adult patients who underwent a LVHR with an expanded polytetrafluoroethylene mesh
(ePTFE) between January 2003 and July 2014 were reviewed. Those who underwent an
abdominal computed tomography (CT) scan more than 3 months afterwards (n = 166)
were included and their scans were analysed. The primary outcome measure was the
prevalence of a PPS and its characteristics. The secondary outcome measures were
identification of significantly related factors and independent predictors of
PPS. RESULTS: A PPS was observed in 14 of 166 analysed CT scans (8.4%). Eleven
patients were symptomatic; conservative treatment (wait-and-see policy) was
successful in eight. Three underwent relaparoscopy with removal of a thick
neoperitoneum. Several instances of tack and/or mesh detachment were identified
on CT scans and during relaparoscopy. Independent predictors were: > 3 trocars
(RR 5.0, 95% CI 1.6-15.8) and use of a mesh larger than > 300 cm2 (RR 9.9, 95% CI
1.9-51.2). CONCLUSIONS: A PPS is a relatively common complication after LVHR with
an ePTFE mesh of usually larger hernias. A "wait-and-see" approach seems
justified in most cases. Some require laparoscopic excision of the thick
neoperitoneum. A PPS can cause tack and mesh detachment but the clinical
consequences are unclear. Recurrences have not been observed in this series.
PMID- 29335910
TI - Duration and magnitude of postoperative risk of venous thromboembolism after
planned inguinal hernia repair in men: a population-based cohort study.
AB - PURPOSE: Little is known regarding the magnitude and timing of the risk of VTE
following inguinal hernia surgery. We aimed to determine the absolute and
relative rates of venous thromboembolism (VTE) following planned inguinal hernia
repair. METHODS: We analysed male adults with a first inguinal hernia repair with
no prior record of VTE from the Clinical Practice Research Datalink, linked to
the Hospital Episode Statistics (2001-2011). Crude rates and adjusted hazard
ratios (HR) of the first VTE were calculated using Cox regression analysis to
compare specific time periods following the surgery compared to the general
population. RESULTS: We identified 28,782 men who underwent an inguinal hernia
repair with 53 (0.18%) having a first VTE in the 90 days following surgery. The
overall rate of VTE in the first 90 days following surgery was 7.61 per 1000
person years (pyrs) (95% CI 5.82-9.96). Increasing age, a body mass index > 30
kg/m2 and an in-patient procedure were associated with an increased risk of VTE,
when compared to the general population. The risk of VTE was highest in the 1st
month following the surgery with a 2.3- (aHR 2.33; 95% CI 1.09-4.99) and 3.5-
(aHR 3.47; 95% CI 2.07-5.83) fold increased risk compared to the general
population for both day case and planned in-patient procedures, respectively.
CONCLUSIONS: Reassuringly, the absolute rates of VTE following inguinal hernia
repair are low. Patients should be informed that their peak risk of VTE is during
the 1st month following the surgery. Further studies on the optimum duration of
thromboprophylaxis following surgery are required in high-risk patients
undergoing hernia repair.
PMID- 29335911
TI - Biotechnology software in the digital age: are you winning?
AB - There is a digital revolution taking place and biotechnology companies are slow
to adapt. Many pharmaceutical, biotechnology, and industrial bio-production
companies believe that software must be developed and maintained in-house and
that data are more secure on internal servers than on the cloud. In fact, most
companies in this space continue to employ large IT and software teams and
acquire computational infrastructure in the form of in-house servers. This is due
to a fear of the cloud not sufficiently protecting in-house resources and the
belief that their software is valuable IP. Over the next decade, the ability to
quickly adapt to changing market conditions, with agile software teams, will
quickly become a compelling competitive advantage. Biotechnology companies that
do not adopt the new regime may lose on key business metrics such as return on
invested capital, revenue, profitability, and eventually market share.
PMID- 29335912
TI - Unprecedented response to combination BRAF and MEK inhibitors in adult anaplastic
ganglioglioma.
PMID- 29335913
TI - Analyzing the interactions of mRNAs, miRNAs, lncRNAs and circRNAs to predict
competing endogenous RNA networks in glioblastoma.
AB - Cross-talk between competitive endogenous RNAs (ceRNAs) may play a critical role
in revealing potential mechanisms of tumor development and physiology.
Glioblastoma is the most common type of malignant primary brain tumor, and the
mechanisms of tumor genesis and development in glioblastoma are unclear. Here, to
investigate the role of non-coding RNAs and the ceRNA network in glioblastoma, we
performed paired-end RNA sequencing and microarray analyses to obtain the
expression profiles of mRNAs, lncRNAs, circRNAs and miRNAs. We identified that
the expression of 501 lncRNAs, 1999 mRNAs, 2038 circRNAs and 143 miRNAs were
often altered between glioblastoma and matched normal brain tissue. Gene ontology
and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed on
these differentially expressed mRNAs and miRNA-mediated target genes of lncRNAs
and circRNAs. Furthermore, we used a multi-step computational framework and
several bioinformatics methods to construct a ceRNA network combining mRNAs,
miRNAs, lncRNAs and circRNA, based on co-expression analysis between the
differentially expressed RNAs. We identified that plenty of lncRNAs, CircRNAs and
their downstream target genes in the ceRNA network are related to glutamatergic
synapse, suggesting that glutamate metabolism is involved in glioma biological
functions. Our results will accelerate the understanding of tumorigenesis, cancer
progression and even therapeutic targeting in glioblastoma.
PMID- 29335914
TI - Accuracy and trending of non-invasive hemoglobin measurement during different
volume and perfusion statuses.
AB - The evolution of non-invasive hemoglobin measuring technology would save time and
improve transfusion practice. The validity of pulse co-oximetry hemoglobin (SpHb)
measurement in the perioperative setting was previously evaluated; however, the
accuracy of SpHb in different volume statuses as well as in different perfusion
states was not well investigated. The aim of this work is to evaluate the
accuracy and trending of SpHb in comparison to laboratory hemoglobin (Lab-Hb)
during acute bleeding and after resuscitation. Seventy patients scheduled for
major orthopedic procedures with anticipated major blood loss were included.
Radical-7 device was used for continuous assessment of SpHb, volume status [via
pleth variability index (PVI)] and perfusion status [via perfusion index (PI)].
Lab-Hb and SpHb were measured at three time-points, a baseline reading, after
major bleeding, and after resuscitation. Samples were divided into fluid
responsive and fluid non-responsive samples, and were also divided into high-PI
and low-PI samples. Accuracy of SpHb was determined using Bland-Altman analysis.
Trending of SpHb was evaluated using polar plot analysis. We obtained 210 time
matched readings. Fluid non-responsive samples were 106 (50.5%) whereas fluid
responsive samples were 104 (49.5%). Excellent correlation was reported between
Lab-Hb and SpHb (r = 0.938). Excellent accuracy with moderate levels of agreement
was also reported between both measures among all samples, fluid non-responsive
samples, fluid-responsive samples, high-PI samples, and low-PI samples [Mean bias
(limits of agreement): 0.01 (- 1.33 and 1.34) g/dL, - 0.08 (- 1.27 and 1.11)
g/dL, 0.09 (- 1.36 and 1.54) g/dL, 0.01 (- 1.34 to 1.31) g/dL, and 0.04 (- 1.31
to 1.39) g/dL respectively]. Polar plot analysis showed good trending ability for
SpHb as a follow up monitor. In conclusion, SpHb showed excellent correlation
with Lab-Hb in fluid responders, fluid non-responders, low-PI, and high PI
states. Despite a favorable mean bias of 0.01 g/dL for SpHb, the relatively wide
levels of agreement (- 1.3 to 1.3 g/dL) might limit its accuracy. SpHb showed
good performance as a trend monitor.
PMID- 29335915
TI - Phenylephrine and paradoxically increased muscle tissue oxygenation: is the
mechanism related to local venoconstriction or augmented venous return?
PMID- 29335916
TI - Association between obstructive sleep apnea and non-alcoholic fatty liver
disease: a systematic review and meta-analysis.
AB - The relationship between obstructive sleep apnea (OSA) and non-alcoholic fatty
liver disease (NAFLD) has been an issue of great concern. The primary purpose of
this study was to determine the influence of OSA on the levels of liver enzymes
including alanine transaminase (ALT) and aspartate transaminase (AST). The
secondary purpose was to estimate the effect of OSA on the histological lesions
of NAFLD, such as steatosis, lobular inflammation, ballooning degeneration,
fibrosis, as well as NAFLD activity score (NAS). A systematic literature review
using PubMed, Cochrane Library, Embase, and Ovid technologies from January 2007
to April 2017 was performed, and 9 studies (2272 participants) that met the
selection criteria were evaluated. The present study demonstrated that OSA was
related to ALT levels, but no significant correlation was found with AST levels.
The subgroup analysis showed that the severity of OSA was associated with ALT
levels, not with AST levels. The meta-regression analysis showed that age, sex,
homeostasis model assessment, diabetes mellitus, body mass index, and waist
circumference did not have a significant effect on the levels of ALT and AST. OSA
was also found to be significantly correlated with steatosis, lobular
inflammation, ballooning degeneration, and fibrosis, but was not correlated with
NAS. OSA was independently related to the development and progression of NAFLD in
terms of liver enzyme level and histological alterations. Future studies should
investigate the possible relevant mechanisms, thereby guiding the exploration of
potential therapeutic implications to prevent the progression of disease.
PMID- 29335917
TI - Basal sympathetic predominance in periodic limb movements in sleep after
continuous positive airway pressure.
AB - PURPOSE: This study investigated the basal autonomic regulation in patients with
obstructive sleep apnea (OSA) showing periodic limb movements in sleep (PLMS)
emerging after therapy with continuous positive airway pressure (CPAP). METHODS:
Data of patients with OSA undergoing a first polysomnography for diagnosis and a
second polysomnography for therapy with CPAP were reviewed. Patients with OSA
showing PLMS on the first polysomnography were excluded. By using heart rate
variability analysis, epochs without any sleep events and continuous effects from
the second polysomnography were retrospectively analyzed. RESULTS: Of 125
eligible patients, 30 with PLMS after therapy with CPAP (PLMS group) and 30 not
showing PLMS on both polysomnography (non-PLMS group) were randomly selected for
the analysis. No significant differences in the demographic characteristics and
variables of polysomnographies were identified between the groups. Although one
trend of low root mean square of successive differences (RMSSD) between intervals
of adjacent normal heart beats (NN intervals) in the PLMS group was observed,
patients in the PLMS group had significantly low normalized high-frequency (n-HF)
and high-frequency (HF) values, but high normalized low frequency (n-LF) and high
ratio of LF to HF (LF/HF ratio). After adjustment for confounding variables, PLMS
on the second polysomnography was significantly associated with RMSSD (beta = -
6.7587, p = 0.0338), n-LF (beta = 0.0907, p = 0.0148), n-HF (beta = - 0.0895, p =
0.0163), log LF/HF ratio (beta = 0.4923, p = 0.0090), and log HF (beta = -
0.6134, p = 0.0199). CONCLUSIONS: Patients with OSA showing PLMS emerging after
therapy with CPAP may have a basal sympathetic predominance with potential
negative cardiovascular effects.
PMID- 29335919
TI - Inter- and intracellular colonization of Arabidopsis roots by endophytic
actinobacteria and the impact of plant hormones on their antimicrobial activity.
AB - Many actinobacteria live in close association with eukaryotes such as fungi,
insects, animals and plants. Plant-associated actinobacteria display
(endo)symbiotic, saprophytic or pathogenic life styles, and can make up a
substantial part of the endophytic community. Here, we characterised endophytic
actinobacteria isolated from root tissue of Arabidopsis thaliana (Arabidopsis)
plants grown in soil from a natural ecosystem. Many of these actinobacteria
belong to the family of Streptomycetaceae with Streptomyces olivochromogenes and
Streptomyces clavifer as well represented species. When seeds of Arabidopsis were
inoculated with spores of Streptomyces strain coa1, which shows high similarity
to S. olivochromogenes, roots were colonised intercellularly and, unexpectedly,
also intracellularly. Subsequent exposure of endophytic isolates to plant
hormones typically found in root and shoot tissues of Arabidopsis led to altered
antibiotic production against Escherichia coli and Bacillus subtilis. Taken
together, our work reveals remarkable colonization patterns of endophytic
streptomycetes with specific traits that may allow a competitive advantage inside
root tissue.
PMID- 29335920
TI - Clergy's Beliefs About Mental Illness and Their Perception of Its Treatability:
Experience from a Church-Based Prevention of Mother-to-Child HIV Transmission
(PMTCT) Trial in Nigeria.
AB - Clergy participating in the Healthy Beginning Initiative (N = 45), a program
utilizing church workers to integrate packages of care into church activities,
completed a 43-item self-administered questionnaire assessing their attitudes and
beliefs about mental disorders and perception of their treatability. A majority
believed that drug/alcohol use, stress and genetic inheritance could cause mental
illness and that society needed to adopt more tolerant attitude toward people
with mental disorders. Clergy with contact with people with mental disorders were
more likely to perceive depression as treatable. In conclusion, participants had
positive attitudes toward mental disorders with some believing that they are
treatable.
PMID- 29335921
TI - Development of real-time PCR assay for the detection of Mycoplasma bovis.
AB - Mycoplasma bovis is one of the important bovine mycoplasma involved in
economically important clinical conditions like respiratory diseases, otitis
media, and mastitis. The present study was undertaken with the objective of
developing a SYBR Green dye-based real-time PCR assay targeting uvrC gene for the
diagnosis of M. bovis. The analytical sensitivity and specificity of the assay
were evaluated. The test showed 103-fold more sensitivity than conventional PCR
and detected down to 100 fg level of DNA. It was found to be specific, as no
cross reactivity was shown with other related bacteria and Mycoplasma species.
The developed assay was able to detect down to 40 copies of uvrC gene from spiked
bovine milk samples. At present, this developed assay may be used as a valuable
diagnostic tool for the detection of Mycoplasma bovis.
PMID- 29335922
TI - Breast conserving surgery in combination with intraoperative radiotherapy after
previous external beam therapy: an option to avoid mastectomy.
AB - PURPOSE: Mastectomy is the standard procedure in patients with in-breast tumor
recurrence (IBTR) or breast cancer after irradiation of the chest due to
Hodgkin's disease. In certain cases a second breast conserving surgery (BCS) in
combination with intraoperative radiotherapy (IORT) is possible. To date, data
concerning BCS in combination with IORT in pre-irradiated patients are limited.
This is the first pooled analysis of this special indication with a mature follow
up of 5 years. METHODS: Patients with IBTR after external beam radiotherapy
(EBRT; treated in two centers) for breast cancer were included. Patients with
previous EBRT including the breast tissue due to other diseases were also
included. IORT was performed with the IntrabeamTM-device using low kV X-rays.
Clinical data including outcome for all patients and toxicity for a
representative cohort (LENT-SOMA scales) were obtained. Statistical analyses were
done including Kaplan-Meier estimates for local recurrence, distant metastasis
and overall survival. RESULTS: A total of 41 patients were identified (39
patients with IBTR, 2 with Hodgkin's disease in previous medical history). Median
follow-up was 58 months (range 4-170). No grade 3/4 acute toxicity occurred
within 9 weeks. Local recurrence-free survival rate was 89.9% and overall
survival was 82.7% at 5 years. Seven patients developed metastasis within the
whole follow-up. CONCLUSIONS: BCS in combination with IORT in IBTR in pre
irradiated patients is a feasible method to avoid mastectomy with a low risk of
side effects and an excellent local control and good overall survival.
PMID- 29335923
TI - How reliable are the available safety data on hormonal stimulation for fertility
preservation in young women with newly diagnosed early breast cancer?
PMID- 29335924
TI - BRCA1 and BRCA2 germline variants in breast cancer patients from the Republic of
Macedonia.
AB - PURPOSE: We aimed to establish the spectrum of BRCA1/2 mutations among the breast
cancer (BC) patients from the Republic of Macedonia. METHODS: We used targeted
next-generation sequencing (NGS), Sanger DNA sequencing, and multiplex ligation
probe amplification analysis (MLPA) to search for point mutations and
deletions/duplications involving BRCA1 and BRCA2-coding regions. RESULTS: We have
analyzed a total of 313 BC patients, enriched for family history of cancer, early
age of onset and bilateral and/or triple negative (TN) BC. A total of 26
pathogenic mutations were observed in 49 unrelated BC patients (49/313, 15.7%).
BRCA2 mutations (27/49, 55.1%) were more common than BRCA1 mutations (22/49,
44.9%). We identified five novel point mutations, one in BRCA1 (c.4352_4356delA)
and four in BRCA2 (c.151G>T, c.4707_4708delCA, c.7811_7814delTGTG, and
c.9304_9305delG), as well as two novel deletions involving parts of the BRCA1
gene (c.81-?_593+?del and c.5470-?_5530+?del). The most common mutations were
c.181T>G, c.5266dupC, and c.3700_3704del5 in BRCA1 and c.7879A>T,
c.8317_8330del14 and c.5722_5723delCT in BRCA2 gene. Thus far, BRCA2 c.7879A>T
and c.8317_8330del14 mutations have been described in several isolated cases;
however, our study is the first one showing that they have a founder effect among
Macedonian population. Nine recurrent mutations account for 65.3% of all of the
detected mutations allowing for implementation of a fast first-step BRCA1/2
mutational screening strategy in our country. CONCLUSION: This study provides a
comprehensive view of known and novel BRCA1/2 mutations in BC patients from the
Republic of Macedonia and contributes to the global spectrum of BRCA1/2 mutations
in breast cancer.
PMID- 29335925
TI - Germline deleterious mutations in genes other than BRCA2 are infrequent in male
breast cancer.
AB - PURPOSE: Male breast cancer (MBC) is a rare cancer entity, with mutations in
BRCA1 and BRCA2 genes accounting for ~ 10% of patients. Multiple-gene sequencing
has already entered clinical practice for female breast cancer, whereas the
performance of panel testing in MBC has not been studied extensively. Therefore,
the aim of this study was to evaluate the clinical utility of panel testing for
MBC, by the largest gene panel used so far, through investigation of patients
deriving from a population with known founder effects. METHODS: Genomic DNA from
one hundred and two Greek MBC patients, unselected for age and family history,
was used to prepare libraries which capture the entire coding regions of 94
cancer genes. RESULTS: Loss-of-function (LoF) mutations were found in 12.7% of
the cases, distributed in six genes: BRCA2, ATM, BRCA1, CHEK2, PMS2, and FANCL.
BRCA2 mutations were the most frequent, followed by ATM mutations, accounting for
6.9 and 2%, respectively, while mutations in other genes were detected in single
cases. Age at diagnosis or family history was not predictive of mutation status.
Beyond mutations in established breast cancer predisposing genes, LoF mutations
in PMS2 and FANCL among MBC patients are reported here for the first time.
CONCLUSIONS: Our findings, using the largest gene panel for MBC patients so far,
indicate that BRCA testing should be the primary concern for MBC patients. Until
sufficient evidence arises from larger studies, multiple-gene panels may be of
limited benefit for MBC and their families, at least for MBC patients of specific
descent.
PMID- 29335926
TI - ?
PMID- 29335927
TI - miRNAs as Potential Treatment Targets and Treatment Options in Cancer.
AB - Standard cancer therapies for solid malignancies, such as chemotherapy and
radiotherapy, are not target specific against cancer cells and are often not
fully efficacious. Chemotherapy and radiotherapy may cause side effects, and the
need to develop additional strategies for cancer treatment is urgent. MicroRNAs
(miRNAs) are small non-coding RNAs with heterogeneous functions and have been
described in almost every known cancer model. Besides their basic tumor
suppressive and oncogenic functions, they also have the potential to modulate
chemotherapy and radiotherapy and to be manipulated with chemical compounds to
make them chemically suitable for efficient delivery to cancer cells. It has been
suggested that the level of expression of specific miRNAs could increase
treatment efficacy by determining the stage of chemotherapy/radiotherapy
sensitivity. Application of miRNAs alone or in combination with standard
therapeutic strategies may significantly improve the success of cancer treatments
in the future.
PMID- 29335928
TI - CT imaging of primary pancreatic lymphoma: experience from three referral centres
for pancreatic diseases.
AB - PURPOSE: To describe CT characteristics of primary pancreatic lymphoma (PPL), a
rare disease with features in common with adenocarcinoma. MATERIALS AND METHODS:
Fourteen patients were enrolled. CT: unenhanced scan, contrast-enhanced
pancreatic and venous phases. Image analysis: tumour location; peri-pancreatic
vessel encasement; necrosis; enlarged lymph nodes; fat stranding; enlarged bile
duct and pancreatic duct; neoplasm longest dimension, volume and density.
RESULTS: Histopathological diagnoses: follicular non-Hodgkin lymphoma (5/14),
diffuse large B-cell lymphoma (6/14) and high-grade B-cell lymphoma not otherwise
specified (3/14). Six of 14 PPLs were located in the pancreatic head and 7/14 in
the body-tail; 1/14 involved the whole gland. In 5/14 cases the superior
mesenteric artery and vein were encased; splenic vein and artery encasement was
depicted in 2 PPLs. Necrosis was present in 2/14. Enlarged retroperitoneal lymph
nodes were found in 11 cases and fat stranding in all patients. The bile duct was
dilated in six cases and the pancreatic duct in five. Mean neoplasm longest
diameter and volume were 8.05 cm and 210.8 cm3. Mean tumour attenuation values
were 39.1 HU at baseline, 60.6 HU in the pancreatic phase and 71.4 HU in the
venous phase. CONCLUSIONS: PPL presents as a large mass lesion with delayed
homogeneous enhancement; peri-pancreatic fat stranding and vessel encasement are
present, without vascular infiltration. Pancreatic duct dilatation is rare. KEY
POINTS: * Primary pancreatic lymphoma (PPL) is a rare haematological disease *
PPL presents imaging features in common with pancreatic carcinoma but also some
distinctive findings * The majority of PPLs are large lesions with delayed
homogeneous enhancement * Peri-pancreatic fat stranding and vessel encasement are
common in PPL * Vascular infiltration and pancreatic duct dilatation are rare in
PPL.
PMID- 29335930
TI - [Comments and supplement : Leukopenia and agranulocytosis under antirheumatic
drug treatment in HLA B27 positive patients].
PMID- 29335929
TI - Computational model to investigate the relative contributions of different
neuromuscular properties of tibialis anterior on force generated during ankle
dorsiflexion.
AB - This study describes a new model of the force generated by tibialis anterior
muscle with three new features: single-fiber action potential, twitch force, and
pennation angle. This model was used to investigate the relative effects and
interaction of ten age-associated neuromuscular parameters. Regression analysis
(significance level of 0.05) between the neuromuscular properties and
corresponding simulated force produced at the footplate was performed.
Standardized slope coefficients were computed to rank the effect of the
parameters. The results show that reduction in the average firing rate is the
reason for the sharp decline in the force and other factors, such as number of
muscle fibers, specific force, pennation angle, and innervation ratio. The fast
fiber ratio affects the simulated force through two significant interactions.
This study has ranked the individual contributions of the neuromuscular factors
to muscle strength decline of the TA and identified firing rate decline as the
biggest cause followed by decrease in muscle fiber number and specific force. The
strategy for strength preservation for the elderly should focus on improving
firing rate. Graphical abstract Neuromuscular properties of Tibialis Anterior on
force generated during ankle dorsiflexion.
PMID- 29335931
TI - [Indications for joint replacement : Knee arthroplasty].
AB - Current demographic trends with an increasing number of older patients, have led
to a rising number of patients with higher demands on performance. Osteoarthritis
in younger patients caused by abnormal forms or accidents also pose new
challenges for medical professionals in the orthopedic field. As a rule of thumb,
all conservative therapeutic possibilities should be exhausted before starting a
surgical intervention. The main aims of surgery are to reduce pain, increase
mobility and quality of life. In order to qualify for total knee arthroplasty
(TKA) patients must fulfil major and minor criteria; however, after TKA
approximately one fifth of patients are not satisfied with the result. In order
to reduce this rate, indications should be narrowly set and expectations should
be thoroughly discussed with the patient prior to an intervention. The high
degree of dissatisfaction must be improved by intensifying efforts in further
research.
PMID- 29335932
TI - The EURO-FORTA (Fit fOR The Aged) List: International Consensus Validation of a
Clinical Tool for Improved Drug Treatment in Older People.
AB - BACKGROUND: Drug treatment of older people is still potentially inappropriate in
many cases as multimorbidity and related polypharmacy are highly prevalent. To
increase the quality of drug treatment in older people, the FORTA (Fit fOR The
Aged) List (first version 2012) was developed in a Delphi consensus procedure and
updated (FORTA2015) by 21 experts from Germany and Austria. It has been validated
in a randomized, controlled, prospective trial demonstrating significant
improvement in the quality of drug treatment and clinical endpoints (VALFORTA).
METHODS: Based on these results, Delphi consensus validations (two rounds) of
country/region-specific FORTA Lists were conducted in the UK/Ireland, France,
Poland, Italy, Spain, the Nordic countries and The Netherlands. An algorithm
based on geriatric/pharmacologic expertise, publications and professional
position was used to find experts in the field. RESULTS: Forty-seven experts
agreed to participate in the Delphi process (return rate of 97.9%). For each
country/region, the overall mean consensus coefficient (deviation from the
initiator proposal) was > 0.9. FORTA Lists from six countries/regions with a
minimum of four participating experts (excluding The Netherlands) plus the
original FORTA List were collated into the EURO-FORTA List containing 264 items
in 26 main indication groups. Two drugs had to be added to the proposed items, as
proposed by at least four countries/regions; none had to be removed. CONCLUSION:
This project produced seven new country/region-specific FORTA Lists, as well as
the overarching EURO-FORTA List showing a high consensual level based on a
broader expert base. EURO-FORTA should help to spread the FORTA approach and
improve geriatric pharmacotherapy internationally.
PMID- 29335933
TI - Cost-Effectiveness Analysis of Bariatric Surgery for Morbid Obesity.
AB - BACKGROUND: In the USA, three types of bariatric surgeries are widely performed,
including laparoscopic sleeve gastrectomy (LSG), laparoscopic Roux-en-Y gastric
bypass (LRYGB), and laparoscopic adjustable gastric banding (LAGB). However, few
economic evaluations of bariatric surgery are published. There is also scarcity
of studies focusing on the LSG alone. Therefore, this study is evaluating the
cost-effectiveness of bariatric surgery using LRYGB, LAGB, and LSG as treatment
for morbid obesity. METHODS: A microsimulation model was developed over a
lifetime horizon to simulate weight change, health consequences, and costs of
bariatric surgery for morbid obesity. US health care prospective was used. A
model was propagated based on a report from the first report of the American
College of Surgeons. Incremental cost-effectiveness ratios (ICERs) in terms of
cost per quality-adjusted life-year (QALY) gained were used in the model. Model
parameters were estimated from publicly available databases and published
literature. RESULTS: LRYGB was cost-effective with higher QALYs (17.07) and cost
($138,632) than LSG (16.56 QALYs; $138,925), LAGB (16.10 QALYs; $135,923), and no
surgery (15.17 QALYs; $128,284). Sensitivity analysis showed initial cost of
surgery and weight regain assumption were very sensitive to the variation in
overall model parameters. Across patient groups, LRYGB remained the optimal
bariatric technique, except that with morbid obesity 1 (BMI 35-39.9 kg/m2)
patients, LSG was the optimal choice. CONCLUSION: LRYGB is the optimal bariatric
technique, being the most cost-effective compared to LSG, LAGB, and no surgery
options for most subgroups. However, LSG was the most cost-effective choice when
initial BMI ranged between 35 and 39.9 kg/m2.
PMID- 29335934
TI - The Predictive Factors for Diabetic Remission in Chinese Patients with BMI > 30
kg/m2 and BMI < 30 kg/m2 Are Different.
AB - INTRODUCTION: Roux-en-Y gastric bypass has been proven to be beneficial for
patients with obesity and type 2 diabetes mellitus (T2DM). In less-obese patient
(BMI 30-35 kg/m2), surgical treatment is indicated when medication fails to
control the T2DM. Asian develops diabetes at a lower BMI. For lower-BMI patients,
the rate of diabetes amelioration varies significantly with patients of higher
BMI after surgical treatment. The factors that contribute to the post-operative
diabetes response rate in lower-BMI patients have not been elucidated. METHODS:
Between 2010 and 2014, a total of 144 patients who underwent gastric bypass for
the treatment of T2DM were included for study. Patients were divided into two
groups for subgroup analysis, namely BMI > 30 kg/m2 and BMI < 30 kg/m2. Factors
affecting the remission rate were examined. RESULTS: Of the studied patients, the
DM remission rate for the high-BMI group (BMI > 30 kg/m2) was 80% (n = 90)
whereas for the lower BMI (BMI < 30 kg/m2) was 50% (n = 54), p < 0.001. For high
BMI group, low HbA1c and high fasting C-peptide are predictive factors whereas
for lower-BMI group, along with elevated C-peptide level, disease duration is the
positive predictive factor for DM remission. CONCLUSION: Patients with BMI > 30
kg/m2 and those with BMI < 30 kg/m2 have distinct remission predicting factors.
Low HbA1c is a predictor of remission in low-high-BMI patients while duration of
diabetes is for high-low-BMI patients. C-peptide is a predictor of remission in
both groups. Further large-scale studies are required to define the predictors of
diabetes remission after gastric bypass in low- and high-BMI patients.
PMID- 29335935
TI - ?
PMID- 29335936
TI - ?
PMID- 29335937
TI - ?
PMID- 29335938
TI - [Diabetes and infection - a missing link really?]
PMID- 29335939
TI - [E-cigarettes: in urgent cases an acceptable alternative].
PMID- 29335940
TI - [The human intestinal microbiome and why you have to think twice before
prescribing antibiotics!]
PMID- 29335941
TI - ?
PMID- 29335942
TI - [Lipoprotein (a) - what to do?]
PMID- 29335943
TI - [PCSK9 inhibitors: For which patients? For which indication? What to consider?]
PMID- 29335944
TI - [Statin-associated muscle symptoms].
PMID- 29335945
TI - ?
PMID- 29335946
TI - ?
PMID- 29335947
TI - ?
PMID- 29335948
TI - ?
PMID- 29335949
TI - ?
PMID- 29335951
TI - ?
PMID- 29335950
TI - ?
PMID- 29335952
TI - ?
PMID- 29335953
TI - ?
PMID- 29335954
TI - ?
PMID- 29335955
TI - ?
PMID- 29335956
TI - ?
PMID- 29335957
TI - ?
PMID- 29335958
TI - ?
PMID- 29335959
TI - ?
PMID- 29335960
TI - ?
PMID- 29335961
TI - ?
PMID- 29335962
TI - ?
PMID- 29335964
TI - ?
PMID- 29335963
TI - ?
PMID- 29335965
TI - ?
PMID- 29335966
TI - ?
PMID- 29335967
TI - ?
PMID- 29335968
TI - ?
PMID- 29335969
TI - ?
PMID- 29335970
TI - ?
PMID- 29335972
TI - ?
PMID- 29335971
TI - ?
PMID- 29335973
TI - ?
PMID- 29335974
TI - ?
PMID- 29335975
TI - ?
PMID- 29335976
TI - ?
PMID- 29335977
TI - ?
PMID- 29335978
TI - ?
PMID- 29335980
TI - ?
PMID- 29335982
TI - ?
PMID- 29335981
TI - ?
PMID- 29335983
TI - ?
PMID- 29335985
TI - ?
PMID- 29335984
TI - ?
PMID- 29335986
TI - ?
PMID- 29335987
TI - ?
PMID- 29335989
TI - ?
PMID- 29335990
TI - ?
PMID- 29335988
TI - ?
PMID- 29335992
TI - ?
PMID- 29335993
TI - ?
PMID- 29335991
TI - ?
PMID- 29335995
TI - ?
PMID- 29335994
TI - ?
PMID- 29335996
TI - ?
PMID- 29335997
TI - ?
PMID- 29335998
TI - ?
PMID- 29335999
TI - [Rheumatoid arthritis].
PMID- 29336000
TI - The Origin and Ecological Function of an Ion Inducing Anti-Predator Behavior in
Lithobates Tadpoles.
AB - In aquatic environments, chemical cues are believed to be associated with prey
response to predation risk, yet few basic cue compositions are known despite the
pronounced ecological and evolutionary significance of such cues. Previous work
indicated that negatively-charged ions of m/z 501 are possibly a kairomone that
induces anti-predator responses in amphibian tadpoles. However, work described
here confirms that this specific ion species m/z 501.2886 is produced by injured
tadpoles, exhibits increased spectral intensity with higher tadpole biomass, and
is not produced by starved predators. These results indicate the anion is an
alarm cue released from tadpoles. High resolution mass spectrometry (HR-MS)
revealed a unique elemental composition for [M-H]-, m/z 501.2886, of C26H45O7S-
which could not be determined in previous studies using low resolution
instruments. Collision induced dissociation of m/z 501 ions formed product ions
of m/z 97 and m/z 80, HSO4- and SO3-, respectively, showing the presence of
sulfate. Green frog tadpoles, Lithobates clamitans, exposed to the m/z 501 anion
or sodium dodecyl sulfate exhibited similar anti-predator responses, suggesting
organic sulfate is a tadpole behavior modifier.
PMID- 29336001
TI - Advances in the Study of the Middle Cranial Fossa through Cutting Edge
Neuroimaging Techniques.
AB - The objective of this paper is to present a morphometric study of the middle
cranial fossa from the study of 87 patients using cutting edge multislice
computed tomography scans (32 detectors) and Magnetic Resonance Imaging. The
study presents a detailed anatomical-radiological and morphometric analysis of
the middle cranial fossa as well as its neurovascular elements in normal
conditions. The implications of this investigation in training and clinical
contexts are discussed.
PMID- 29336003
TI - Prevalence of pre-school children for overweight/obesity in Turkey.
AB - BACKGROUND: Most of the studies and interventions are targeted to address
undernutrition, but childhood obesity has become a silent killer among children.
Developing countries, including Turkey, could recognize the importance of the
issue now and have begun to discuss the necessity of studies on this subject.
Therefore, this study aims to examine the prevalence of obesity among pre-school
children in Turkey. METHODS: The data source of this study is the Turkey
Demographic and Health Survey (TDHS)-2013. The TDHS-2013 was a sample study to
gather information about the fertility levels and changes in them, infant and
child mortality, family planning, and maternal and infant health at the national
level. RESULTS: Overweight/obesity for height was 8.6% and 6.6% for age.
Overweight/obesity problems are mostly observed in the West and are higher in
urban areas. Overweight/obesity decreases with increasing age. There is a
positive correlation between overweight/obesity and maternal educational level.
As the household welfare level increases, overweight/obesity increases in pre
school children. Female children are at higher risk of overweight/obesity than
males. As birth order increases, overweight/obesity decreases. Children living in
other regions have overweight/obesity problems more than the pre-school children
living in the East. CONCLUSIONS: This study speculates that obesity appears to be
a major problem among pre-school children in Turkey. Based on the findings, the
current situation of overweight/obesity among pre-school children is so close to
many developing and developed countries, whose obesity levels are a greater
concern. This finding demonstrates that effective interventions of obesity should
begin as early as infancy in Turkey, as it is a developing country.
PMID- 29336002
TI - Body composition and circulating estradiol are the main bone density predictors
in healthy young and middle-aged men.
AB - PURPOSE: Current fracture risk assessment options in men call for improved
evaluation strategies. Recent research directed towards non-classic bone mass
determinants have often yielded scarce and conflicting results. We aimed at
investigating the impact of novel potential bone mass regulators together with
classic determinants of bone status in healthy young and middle-aged men.
METHODS: Anthropometric measurements, all-site bone mineral density (BMD) and
body composition parameters assessed by dual-energy X-ray absorptiometry and also
serum concentrations of (1) the adipokines leptin and resistin, (2) vitamin D and
parathormone (PTH), (3) sex hormone binding globulin (SHBG), total testosterone
and estradiol (free testosterone was also calculated) and (4) C-terminal
telopeptide of type I collagen (CTx) were obtained from 30 apparently healthy
male volunteers aged 20-65 years enrolled in this cross-sectional study. RESULTS:
Only lean mass (LM) and total estradiol independently predicted BMD in men in
multiple regression analysis, together explaining 49% (p <= 0.001) of whole-body
BMD variance. Hierarchical regression analysis with whole-body BMD as outcome
variable demonstrated that the body mass index (BMI) beta coefficient became
nonsignificant when LM was added to the model. Adipokines, fat parameters,
testosterone (total and free), SHBG, PTH and vitamin D were not independently
associated with BMD or CTx. CONCLUSIONS: The present study shows that LM and sex
hormones-namely estradiol-are the main determinants of bone mass in young and
middle-aged men. The effects of BMI upon BMD seem to be largely mediated by LM.
Lifestyle interventions should focus on preserving LM in men for improved bone
outcomes.
PMID- 29336004
TI - Point-of-Care Urine Ethyl Glucuronide Testing to Detect Alcohol Use Among HIV
Hepatitis B Virus Coinfected Adults in Zambia.
AB - In an HIV-hepatitis B virus (HIV-HBV) coinfection cohort in Zambia, we piloted a
qualitative point-of-care (POC) test for urine Ethyl glucuronide (uEtG), assessed
concordance between uEtG and alcohol use disorders identification test
consumption (AUDIT-C), and identified epidemiological factors associated with
underreporting (defined as uEtG-positivity with last reported drink > 7 days
prior). Among 211 participants (40.8% women), there were 44 (20.8%) lifetime
abstainers, 32 (15.2%) former drinkers, and 135 (64.0%) current drinkers,
including 106 (50.2%) with unhealthy drinking per AUDIT-C. Eighty-seven (41.2%)
were uEtG-positive including 64 of 65 (98.5%) who drank <= 3 days prior and 17 of
134 (12.7%) underreported, all of whom admitted to recent drinking when results
were discussed. uEtG was moderately concordant with AUDIT-C. Past drinking
(versus lifetime abstinence) and longer time on antiretrovirals (>= 12 months)
were associated with underreporting. These data support further use of POC
alcohol biomarkers in HIV and hepatitis research and clinical settings.
PMID- 29336006
TI - The place of frailty and vulnerability in the surgical risk assessment: should we
move from complexity to simplicity?
AB - Due to aging of the world population, older patients accessing health services
are becoming continuously more frequent. This has increased the interest in
assessing frailty and vulnerability in all specialties and general medicine.
Although the term frailty has been recognized for over 30 years, there is not yet
a universally recognized definition, and different care providers assess frailty
and vulnerability with dissimilar tools, from very complex to very simple
validated scales. Being treated with respect and dignity at the right time and
place is the key message, as well as after undergoing a global evaluation both in
urgency/emergency and in programmed surgery for all older surgical patients.
Filling the gap will improve the results of any clinical intervention, both
medical and surgical. Anesthesiologists, surgeons, hospitalists, and any member
of the team of care providers must be trained into geriatric syndromes.
PMID- 29336005
TI - Degranulation inhibitors from the arils of Myristica fragrans in antigen
stimulated rat basophilic leukemia cells.
AB - A methanol extract of mace, the aril of Myristica fragrans (Myristicaceae), was
found to inhibit the release of beta-hexosaminidase, a marker of antigen-IgE
stimulated degranulation in rat basophilic leukemia cells (RBL-2H3, IC50 = 45.7
MUg/ml). From the extract, three new 8-O-4' type neolignans, maceneolignans I-K
(1-3), were isolated, and the stereostructures of 1-3 were elucidated based on
spectroscopic and chemical evidence. Among the isolates, maceneolignans A (5), D
(6), and H (8), (-)-(8R)-?8'-4-hydroxy-3,3',5'-trimethoxy-8-O-4'-neolignan (13),
(-)-(8R)-?8'-3,4,5,3',5'-pentamethoxy-8-O-4'-neolignan (14), (-)-erythro-(7R,8S)
?8'-7-acetoxy-3,4-methylenedioxy-3',5'-dimethoxy-8-O-4'-neolignan (17), (+)
licarin A (20), nectandrin B (24), verrucosin (25), and malabaricone C (29) were
investigated as possible degranulation inhibitors (IC50 = 20.7-63.7 MUM). These
inhibitory activities were more potent than those of the antiallergic agents
tranilast (282 MUM) and ketotifen fumalate (158 MUM). Compounds 5, 25, and 29
also inhibited antigen-stimulated tumor necrosis factor-alpha production (IC50 =
39.5-51.2 MUM), an important process in the late phase of type I allergic
reactions.
PMID- 29336007
TI - Vulvo-vaginal rejuvenation: Fact or fiction? Fractional carbon dioxide laser for
genitourinary syndrome of menopause.
PMID- 29336008
TI - Dermatology training across the globe.
PMID- 29336009
TI - Gefitinib for advanced non-small cell lung cancer.
AB - BACKGROUND: The role of gefitinib for the treatment of advanced non-small cell
lung cancer (NSCLC) is evolving. We undertook a systematic review to evaluate the
available evidence from all randomised trials. OBJECTIVES: To determine the
effectiveness and safety of gefitinib as first-line, second-line or maintenance
treatment for advanced NSCLC. SEARCH METHODS: We performed searches in CENTRAL,
MEDLINE and Embase from inception to 17 February 2017. We handsearched relevant
conference proceedings, clinical trial registries and references lists of
retrieved articles. SELECTION CRITERIA: We included trials assessing gefitinib,
alone or in combination with other treatment, compared to placebo or other
treatments in the first- or successive-line treatment of patients with NSCLC,
excluding compassionate use. DATA COLLECTION AND ANALYSIS: We used the standard
Cochrane methodology. Two authors independently assessed the search results to
select those with sound methodological quality. We carried out all analyses on an
intention-to-treat basis. We recorded the following outcome data: overall
survival, progression-free survival, toxicity, tumour response and quality of
life. We also collected data for the following subgroups: Asian ethnicity and
positive epidermal growth factor receptor (EGFR) mutation. MAIN RESULTS: We
included 35 eligible randomised controlled trials (RCTs), which examined 12,089
patients.General populationGefitinib did not statistically improve overall
survival when compared with placebo or chemotherapy in either first- or second
line settings. Second-line gefitinib prolonged time to treatment failure (TTF)
(hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.75 to 0.90, P < 0.0001)
when compared with placebo. Maintenance gefitinib improved progression-free
survival (HR 0.70, 95% CI 0.53 to 0.91, P = 0.007) after first-line
therapy.Studies in patients of Asian ethnicity or that conducted subgroup
analysesSecond-line gefitinib prolonged overall survival over placebo (HR 0.66,
95% CI 0.48 to 0.91, P = 0.01). In the first-line setting, progression-free
survival was improved with gefitinib over chemotherapy alone (HR 0.65, 95% CI
0.43 to 0.98, P = 0.04, moderate quality of evidence). Gefitinib given in
combination with a chemotherapy regimen improved progression-free survival versus
either gefitinib alone or chemotherapy alone (HR 0.69, 95% CI 0.49 to 0.96, P =
0.03; HR 0.69, 95% CI 0.62 to 0.77, P < 0.00001, respectively). In the second
line setting, progression-free survival was superior in patients given gefitinib
over placebo or chemotherapy (HR 0.69, 95% CI 0.52 to 0.91, P = 0.009; HR 0.71,
95% CI 0.57 to 0.88, P = 0.002; moderate quality of evidence, respectively).
Combining gefitinib with chemotherapy in the second-line setting was superior to
gefitinib alone (HR 0.65, 95% CI 0.43 to 0.97, P = 0.04). As maintenance therapy,
gefitinib improved progression-free survival when compared with placebo (HR 0.42,
95% CI 0.33 to 0.54, P < 0.00001).Patients with EGFR mutation-positive
tumoursStudies in patients with EGFR mutation-positive tumours showed an
improvement in progression-free survival in favour of gefitinib over first-line
and second-line chemotherapy (HR 0.47, 95% CI 0.36 to 0.61, P < 0.00001; HR 0.24,
95% CI 0.12 to 0.47, P < 0.0001, respectively). Gefitinib as maintenance therapy
following chemotherapy improved overall and progression-free survival (HR 0.39,
95% CI 0.15 to 0.98, P = 0.05; HR 0.17, 95% CI 0.07 to 0.41, P < 0.0001,
respectively) in one phase III study when compared to placebo.Toxicities from
gefitinib included skin rash, diarrhoea and liver transaminase derangements.
Toxicities from chemotherapy included anaemia, neutropenia and neurotoxicity.In
terms of quality of life, gefitinib improved Functional Assessment of Cancer
Therapy-Lung (FACT-L) (standardised mean difference (SMD) 10.50, 95% CI 9.55 to
11.45, P < 0.000001), lung cancer subscale (SMD 3.63, 95% CI 3.08 to 4.19, P <
0.00001) and Trial Outcome Index (SMD 9.87, 95% CI 1.26 to 18.48, P < 0.00001)
scores when compared with chemotherapy. AUTHORS' CONCLUSIONS: This systematic
review shows that gefitinib, when compared with standard first- or second-line
chemotherapy or maintenance therapy, probably has a beneficial effect on
progression-free survival and quality of life in selected patient populations,
particularly those with tumours bearing sensitising EGFR mutations.Patients with
EGFR mutations lived longer when given maintenance gefitinib than those given
placebo.One study conducted subgroup analysis and showed that gefitinib improved
overall survival over placebo in the second-line setting in patients of Asian
ethnicity. All other studies did not detect any benefit on overall survival. The
data analysed in this review were very heterogenous. We were limited in the
amount of data that could be pooled, largely due to variations in study design.
The risk of bias in most studies was moderate, with some studies not adequately
addressing potential selection, attrition and reporting bias. This heterogeneity
may have an impact on the applicability of the resultsCombining gefitinib with
chemotherapy appears to be superior in improving progression-free survival to
either gefitinib or chemotherapy alone, however further data and phase III
studies in these settings are required.Gefitinib has a favourable toxicity
profile when compared with current chemotherapy regimens. Although there is no
improvement in overall survival, gefitinib compares favourably with cytotoxic
chemotherapy in patients with EGFR mutations with a prolongation of progression
free survival and a lesser side effect profile.
PMID- 29336010
TI - The unique role of executive function skills in predicting Hong Kong
kindergarteners' reading comprehension.
AB - BACKGROUND: Word reading and linguistic comprehension skills are two crucial
components in reading comprehension, according to the Simple View of Reading
(SVR). Some researchers have posited that a third component should be involved in
reading and understanding texts, namely executive function (EF) skills. AIM: This
study was novel in two ways. Not only did we tested EF skills as a predictor of
reading comprehension in a non-alphabetic language (i.e., Chinese) to extend the
theoretical model of SVR, we also examined reading comprehension further in
kindergarten children (age 5) in Hong Kong, in the attempt to reveal possible
early precursors of reading comprehension. SAMPLE(S): A group of 170 K3
kindergarteners was recruited in Hong Kong. METHODS: Children's word reading was
assessed. Their linguistic comprehension was assessed with phonological
awareness, verbal short-term memory, and vocabulary knowledge. Using a structured
observation task, Head-Toes-Knees-Shoulders (HTKS), we measured their composite
scores for EF skills. RESULTS: Head-Toes-Knees-Shoulders performance predicted
unique variance in children's Chinese reading comprehension concurrently beyond
word reading and a set of linguistic comprehension skills. CONCLUSIONS: The
results highlight the important role of EF skills in beginning readers' reading
comprehension.
PMID- 29336011
TI - Decreased retinal sensitivity in depressive disorder: a controlled study.
AB - OBJECTIVE: To compare pupil responses in depressed patients with a seasonal
pattern, depressed patients without a seasonal pattern and healthy controls as a
function of daylight hours on the testing day. METHOD: Patients suffering from a
major depressive episode were included in wintertime. The pupil light reflex was
measured at inclusion and in the following summer using a binocular pupillometer.
A protocol of low (1 lux) and high (400 lux) intensity red and blue lights was
used to assess rod, cone and melanopsin-containing intrinsic photosensitive
retinal ganglion cell input to the pupil reflex. RESULTS: The mean group pupil
responses associated with a melanopsin-mediated sustained pupil response at 400
lux blue light were significantly reduced in the depressed subjects (N = 39) as
compared to the healthy controls (N = 24) (P = 0.023). Across all groups, a
reduction in number of daylight hours was significantly associated with a
reduction in sustained pupil response (P = 0.007). All groups showed an equal
effect of daylight hours on the melanopsin-mediated sustained pupil response.
CONCLUSION: The melanopsin-mediated sustained pupil contraction to offset of high
intensity blue light is reduced in depressed patients. These results further
emphasize the interaction of light exposure with depression.
PMID- 29336012
TI - Predictors and consequences of health anxiety symptoms: a novel twin modeling
study.
AB - OBJECTIVE: The question of how to best conceptualize health anxiety (HA) from a
diagnostic and etiological perspective remains debated. The aim was to examine
the relationship between HA and the symptoms of anxiety and obsessive-compulsive
related disorders in a normative twin population. METHOD: Four hundred and ninety
six monozygotic adult twin pairs from the Australian Twin Registry participated
in the study (age, 34.4 +/- 7.72 years; 59% females). Validated scales were used
to assess each domain. We applied a twin regression methodology-ICE FALCON-to
determine whether there was evidence consistent with 'causal' relationships
between HA and other symptoms by fitting and comparing model estimates. RESULTS:
Estimates were consistent with higher levels of obsessing ('unwanted thoughts')
(P = 0.008), social anxiety (P = 0.03), and body dysmorphic symptoms (P = 0.008)
causing higher levels of HA symptoms, and with higher levels of HA symptoms
causing higher levels of physical/somatic anxiety symptoms (P = 0.001).
CONCLUSION: Obsessional thoughts, body dysmorphic concerns, and social anxiety
symptoms may have a causal influence on HA. To report physical/somatic anxiety
appears to be a consequence of the underlying presence of HA-related fears.
Should our results be confirmed by longitudinal studies, the evaluation and
treatment of HA may benefit from the consideration of these identified risk
factors.
PMID- 29336013
TI - Systematic review of atopic dermatitis disease definition in studies using
routinely collected health data.
AB - BACKGROUND: Routinely collected electronic health data obtained for
administrative and clinical purposes are increasingly used to study atopic
dermatitis (AD). Methods for identifying AD patients in routinely collected
electronic health data differ, and it is unknown how this might affect study
results. OBJECTIVES: To evaluate how patients with AD have been identified in
studies using routinely collected electronic health data, to determine whether
these methods were validated and to estimate how the method for identifying
patients with AD affected variability in prevalence estimates. METHODS: We
systematically searched PubMed, Embase and Web of Science for studies using
routinely collected electronic health data that reported on AD as a primary
outcome. Studies of localized AD and other types of dermatitis were excluded. The
protocol for this review was registered in PROSPERO (CRD42016037968). RESULTS: In
total, 59 studies met eligibility criteria. Medical diagnosis codes for inclusion
and exclusion, number of occasions of a code, type of provider associated with a
code and prescription data were used to identify patients with AD. Only two
studies described validation of their methods and no study reported on disease
severity. Prevalence estimates ranged from 0.18% to 38.33% (median 4.91%) and up
to threefold variation in prevalence was introduced by differences in the method
for identifying patients with AD. CONCLUSIONS: This systematic review highlights
the need for clear reporting of methods for identifying patients with AD in
routinely collected electronic health data to allow for meaningful interpretation
and comparison of results.
PMID- 29336014
TI - Response to: Yazdani A. Surgery or in vitro fertilisation: The simplicity of this
question belies its complexity. When all you have is a hammer, everything looks
like a nail.
AB - This is perhaps the most apt mantra of IVF (in vitro fertilisation) as a
treatment in Australasia in this day and age. It is also important to note the
truth in the identification of IVF being low skill-based, largely independent of
the practitioner, but more importantly costly, and with few exceptions, only
available in the private sector. Such revelations really require a rethink of the
entire reproductive endocrinology and infertility (CREI) subspecialty. In fact,
if there is only one solution to all fertility problems - that of the 'effective
IVF procedure' - why not do away completely with the clinician and simply have
nurse practitioners who oversee the identified issue of an individual or couple
wanting a pregnancy? This in conjunction with the outstanding scientific advances
that led to the initiation and promulgation of IVF really would reduce costs by
cutting out the unnecessary clinician middle-person who is unimportant in the
equation. It may be that such cost reduction, the disbandment of the irrelevant
subspecialty and protocol-driven, high-quality fertility checklists would allow
this to be a publically accessible service for all, not just those who can afford
it.
PMID- 29336015
TI - A Metatheory for Cognitive Development (or "Piaget is Dead" Revisited).
AB - In 1997, I argued that with the loss of Piaget's theory as an overarching guide,
cognitive development had become disjointed and a new metatheory was needed to
unify the field. I suggested developmental biology, particularly evolutionary
theory, as a candidate. Here, I examine the increasing emphasis of biology in
cognitive development research over the past 2 decades. I describe briefly the
emergence of evolutionary developmental psychology and examine areas in which
proximal and distal biological causation have been particularly influential. I
argue that developmental biology will continue to increasingly influence research
and theory in cognitive development and that evolutionary theory is well on its
way to becoming a metatheory, not just for cognitive development, but for
developmental psychology generally.
PMID- 29336016
TI - Could conjunctivitis in patients with atopic dermatitis treated with dupilumab be
caused by colonization with Demodex and increased interleukin-17 levels?: reply
from the authors.
PMID- 29336018
TI - The Legacy of Early Abuse and Neglect for Social and Academic Competence From
Childhood to Adulthood.
AB - This study used data from the Minnesota Longitudinal Study of Risk and Adaptation
(N = 267) to investigate whether abuse and neglect experiences during the first 5
years of life have fading or enduring consequences for social and academic
competence over the next 3 decades of life. Experiencing early abuse and neglect
was consistently associated with more interpersonal problems and lower academic
achievement from childhood through adulthood (32-34 years). The predictive
significance of early abuse and neglect was not attributable to the stability of
developmental competence over time, nor to abuse and neglect occurring later in
childhood. Early abuse and neglect had enduring associations with social (but not
academic) competence after controlling for potential demographic confounds and
early sensitive caregiving.
PMID- 29336017
TI - Long-term surveillance of SUDEP in drug-resistant epilepsy patients treated with
VNS therapy.
AB - OBJECTIVE: Limited data are available regarding the evolution over time of the
rate of sudden unexpected death in epilepsy patients (SUDEP) in drug-resistant
epilepsy. The objective is to analyze a database of 40 443 patients with epilepsy
implanted with vagus nerve stimulation (VNS) therapy in the United States (from
1988 to 2012) and assess whether SUDEP rates decrease during the postimplantation
follow-up period. METHODS: Patient vital status was ascertained using the Centers
for Disease Control and Prevention's National Death Index (NDI). An expert panel
adjudicated classification of cause of deaths as SUDEP based on NDI data and
available narrative descriptions of deaths. We tested the hypothesis that SUDEP
rates decrease with time using the Mann-Kendall nonparametric trend test and by
comparing SUDEP rates of the first 2 years of follow-up (years 1-2) to longer
follow-up (years 3-10). RESULTS: Our cohort included 277 661 person-years of
follow-up and 3689 deaths, including 632 SUDEP. Primary analysis demonstrated a
significant decrease in age-adjusted SUDEP rate during follow-up (S = -27 P =
.008), with rates of 2.47/1000 for years 1-2 and 1.68/1000 for years 3-10 (rate
ratio 0.68; 95% confidence interval [CI] 0.53-0.87; P = .002). Sensitivity
analyses confirm these findings. SIGNIFICANCE: Our data suggest that SUDEP risk
significantly decreases during long-term follow-up of patients with refractory
epilepsy receiving VNS Therapy. This finding might reflect several factors,
including the natural long-term dynamic of SUDEP rate, attrition, and the impact
of VNS Therapy. The role of each of these factors cannot be confirmed due to the
limitations of the study.
PMID- 29336019
TI - Computerized planimetry to assess clinical responsiveness in a phase II
randomized trial of topical R333 for discoid lupus erythematosus.
AB - BACKGROUND: R333 is a topical janus kinase and spleen tyrosine kinase inhibitor
being evaluated for discoid lupus erythematosus (DLE) treatment. There is no
validated measure to assess the area of active DLE lesions. OBJECTIVES: To
evaluate R333 efficacy and assess a technique to measure responsiveness. METHODS:
Fifty-four patients with DLE were randomized in a double-blind design to R333 or
placebo. Primary end point was the proportion of patients achieving >= 50%
decrease in erythema and scale based on lesional Cutaneous Lupus Erythematosus
Disease Area and Severity IndexTM for all treated lesions at week 4. Two
dimensional (2D) area measurements for each lesion were recorded at baseline and
weeks 1-6. Eighty-eight photographs (44 pre- and 44 post-treatment) were obtained
from the trial and change in size of active areas was analysed by computerized
planimetry and physician-assessed area change (PAAC). RESULTS: Thirty-six
patients were randomized to R333 and 18 patients were randomized to placebo.
Primary end point was not achieved. There was a strong association between lesion
activity and physician global assessment (P < 0.001). Photos of 42 patients
assessed by computerized planimetry demonstrated excellent inter- and intra-rater
reliability. Area change by computerized planimetry showed a strong correlation
with PAAC (Spearman r = 0.72). Area change by 2D measurements showed a weak
correlation with PAAC (Spearman r = 0.29). CONCLUSIONS: Four weeks of R333
treatment did not result in significant improvement in lesion activity. Lesion
activity and area change using computerized planimetry are better determinants of
responsiveness than area change using 2D measurements.
PMID- 29336021
TI - Evolutionary Developmental Psychology: 2017 Redux.
PMID- 29336020
TI - Return to driving after a diagnosis of epilepsy: A prospective registry study.
AB - OBJECTIVE: To determine the frequency and predictors of return to driving within
1 year after a diagnosis of epilepsy. METHODS: SEISMIC (the Sydney Epilepsy
Incidence Study to Measure Illness Consequences) was a prospective, multicenter,
community-wide study of people of all ages with newly diagnosed epilepsy in
Sydney, Australia. Demographic, socioeconomic, and clinical characteristics and
driving status were obtained as soon as possible after baseline registration with
a diagnosis of epilepsy. Multivariate logistic regression was used to determine
predictors of return to driving at 12-month follow-up. RESULTS: Among 181 (76%)
adult participants (>=18 years old) who reported driving before an epilepsy
diagnosis, 152 provided information on driving at 12 months, of whom 118 (78%)
had returned to driving. Driving for reasons of getting to work or place of
education (odds ratio [OR] = 4.70, 95% confidence intervals [CI] = 1.87-11.86),
no seizure recurrence (OR = 5.15, 95% CI = 2.07-12.82), and being on no or a
single antiepileptic drug (OR = 4.54, 95% CI = 1.45-14.22) were associated with
return to driving (C statistic = 0.79). More than half of participants with
recurrent seizures were driving at follow-up. SIGNIFICANCE: Early return to
driving after a diagnosis of epilepsy is related to work/social imperatives and
control of seizures, but many people with recurrent seizures continue to drive.
Further efforts are required to implement driving restriction policies and to
provide transport options for people with epilepsy.
PMID- 29336022
TI - Nonspecific diffuse alopecia as a single manifestation of syphilis infection:
clinical and trichoscopic features.
PMID- 29336023
TI - Bridging Evolutionary Biology and Developmental Psychology: Toward An Enduring
Theoretical Infrastructure.
AB - Bjorklund synthesizes promising research directions in developmental psychology
using an evolutionary framework. In general terms, we agree with Bjorklund:
Evolutionary theory has the potential to serve as a metatheory for developmental
psychology. However, as currently used in psychology, evolutionary theory is far
from reaching this potential. In evolutionary biology, formal mathematical models
are the norm. In developmental psychology, verbal models are the norm. In order
to reach its potential, evolutionary developmental psychology needs to embrace
formal modeling.
PMID- 29336025
TI - How Children Invented Humanity.
AB - I use the commentaries of Legare, Clegg, and Wen and of Frankenhuis and Tiokhin
as jumping-off points to discuss an issue hinted at both in my essay and their
commentaries: How a developmental perspective can help us achieve a better
understanding of evolution. I examine briefly how neoteny may have contributed to
human morphology; how developmental plasticity in great apes, and presumably our
common ancestor with them, may have led the way to advances in social cognition;
and how the "invention" of childhood contributed to unique human cognitive
abilities. I conclude by acknowledging that not all developmentalists have
adopted an evolutionary perspective, but that we are approaching a time when an
evolutionary perspective will be implicit in the thinking of all psychologists.
PMID- 29336024
TI - Facility and State Variation in Hip Fracture in U.S. Nursing Home Residents.
AB - OBJECTIVES: To quantify the variation in hip fracture incidence across U.S.
nursing home (NH) facilities and states and examine how hip fracture incidence
varies according to facility- and state-level characteristics. DESIGN:
Retrospective cohort using linked national Minimum Data Set assessments; Online
Survey, Certification and Reporting records; and Medicare claims. SETTING: U.S.
NHs with 100 or more beds. PARTICIPANTS: Long-stay NH residents between May 1,
2007, and April 30, 2008, from 1,481 facilities and 46 U.S. states (N = 201,892).
MEASUREMENTS: Incident hip fractures were ascertained using Medicare Part A
diagnostic codes. Each resident was followed for up to 2 years. RESULTS: The mean
adjusted incidence rate of hip fractures for all facilities was 3.13 (95%
confidence interval (CI) = 3.01-3.26) per 100 person-years (range 1.20, 95% CI =
1.15-1.26 to 6.40, 95% CI = 6.07-6.77). Facilities with the highest rates of hip
fracture had greater percentages of residents taking psychoactive medications
(top tertile 27.2%, bottom tertile 24.8%), and fewer nursing (top tertile 3.43,
bottom tertile 3.53) and direct care (top tertile 3.22, bottom tertile 3.29)
hours per day per resident. The combination of state and facility characteristics
explained 6.7% of the variation in hip fracture, and resident characteristics
explained 7.6%. CONCLUSION: Much of the variation in hip fracture incidence
remained unexplained, although these findings indicate that potentially
modifiable state and facility characteristics such as psychoactive drug
prescribing and minimum staffing requirements could be addressed to help reduce
the rate of hip fracture in U.S. NHs.
PMID- 29336026
TI - Youth's Conceptions of Adolescence Predict Longitudinal Changes in Prefrontal
Cortex Activation and Risk Taking During Adolescence.
AB - The development of cognitive control during adolescence is paralleled by changes
in the function of the lateral prefrontal cortex (PFC). Using a three-wave
longitudinal neuroimaging design (N = 22, Mage = 13.08 years at Wave 1), this
study examined if youth's stereotypes about teens modulate changes in their
neural activation during cognitive control. Participants holding stereotypes of
teens as irresponsible in the family context (i.e., ignoring family obligations)
in middle school showed increases in bilateral ventrolateral PFC activation
during cognitive control over the transition to high school, which was associated
with increases in risk taking. These findings provide preliminary evidence that
youth's conceptions of adolescence play a role in neural plasticity over this
phase of development.
PMID- 29336027
TI - Evaluating the validity of subclassifying warfarin-associated nonuremic
calciphylaxis: a retrospective cohort study.
AB - BACKGROUND: Calciphylaxis is a devastating multifactorial disorder of the
subcutaneous fat that is known to be associated with hypercoagulability. Recent
literature has proposed subclassifying patients with calciphylaxis as having
warfarin-associated or warfarin-unassociated disease. AIM: We aimed to determine
whether patients with warfarin-associated calciphylaxis differ clinically from
patients with warfarin-unassociated calciphylaxis. MATERIALS AND METHODS: We
performed a subgroup analysis of patients with nonuremic calciphylaxis from a
previously studied cohort and compared clinical and outcomes features of patients
who were taking warfarin at the time of disease onset to those of patients who
were not. RESULTS: Nineteen patients with nonuremic calciphylaxis were
identified, including 10 (53%) who had been on warfarin at the time of disease
onset and 9 (47%) who had not. Of all clinical and outcomes parameters tested, no
significant differences were detected between the two groups. DISCUSSION AND
CONCLUSIONS: Though this study is limited by its retrospective nature and the
relatively small number of patients studied, available data do not support
subclassifying patients with nonuremic calciphylaxis as having warfarin
associated or warfarin-unassociated disease. Rather, the body of literature would
suggest that identification and correction of underlying disorders of
hypercoagulability should be prioritized.
PMID- 29336028
TI - The role of the head in configural body processing: Behavioural and
electrophysiological evidence from the inversion and scrambling effect.
AB - The present study aimed to further explore the role of the head for configural
body processing by comparing complete bodies with headless bodies and faceless
heads (Experiment 1). A second aim was to further explore the role of the eye
region in configural face processing (Experiment 2). Due to that, we conducted a
second experiment with complete faces, eyeless faces, and eyes. In addition, we
used two effects to manipulate configural processing: the effect of stimulus
inversion and scrambling. The current data clearly show an inversion effect for
intact bodies presented with head and faces including the eye region. Thus, the
head and the eye region seem to be central for configural processes that are
manipulated by the effect of stimulus inversion. Furthermore, the behavioural and
electrophysiological body inversion effect depends on the intact configuration of
bodies and is associated with the N170 as the face inversion effect depends on
the intact face configuration. Hence, configural body processing depends not only
on the presence of the head but rather on a complete representation of human
bodies that includes the body and the head. Furthermore, configural face
processing relies on intact and complete face representations that include faces
and eyes.
PMID- 29336029
TI - Sudden unexpected death in epilepsy in patients treated with brain-responsive
neurostimulation.
AB - OBJECTIVE: To study the incidence and clinical features of sudden unexpected
death in epilepsy (SUDEP) in patients treated with direct brain-responsive
stimulation with the RNS System. METHODS: All deaths in patients treated in
clinical trials (N = 256) or following U.S. Food and Drug Administration (FDA)
approval (N = 451) through May 5, 2016, were adjudicated for SUDEP. RESULTS:
There were 14 deaths among 707 patients (2208 postimplantation years), including
2 possible, 1 probable, and 4 definite SUDEP events. The rate of probable or
definite SUDEP was 2.0/1000 (95% confidence interval [CI] 0.7-5.2) over 2036
patient stimulation years and 2.3/1000 (95% CI 0.9-5.4) over 2208 patient implant
years. Stored electrocorticograms around the time of death were available for 4
patients with probable/definite SUDEP and revealed the following: frequent
epileptiform activity ending abruptly (n = 2), no epileptiform activity or
seizures (n = 1), and an electrographic and witnessed seizure with cessation of
postictal electrocorticography (ECoG) activity associated with apnea and
pulselessness (n = 1). SIGNIFICANCE: The SUDEP rate of 2.0/1000 patient
stimulation years among patients treated with the RNS System is favorable
relative to treatment-resistant epilepsy patients randomized to the placebo arm
of add-on drug studies or with seizures after resective surgery. Our findings
support that treatments that reduce seizures reduce SUDEP risk and that not all
SUDEPs follow seizures.
PMID- 29336030
TI - The aryl hydrocarbon receptor modulates the function of human CD56bright NK
cells.
AB - Human natural killer (NK) cells are divided into two subsets: CD56bright and
CD56dim NK cells, which differ in maturation, function and distribution.
Mechanisms regulating NK cell functions are not completely understood. Aryl
hydrocarbon receptor (AhR) is a ligand-activated transcription factor, that binds
to a variety of endogenous and exogenous molecules, and that has recently been
shown to modulate the function and differentiation of immune cells. Here, we
studied the expression of AhR and its involvement in the regulation of NK cell
functions. We found that AhR mRNA is highly expressed in peripheral CD56bright NK
cells and that AhR mRNA expression gradually decreases as NK cells display a more
mature phenotype. CD56bright NK cells were highly sensitive to AhR ligands.
Specifically, AhR ligands modulated their activation and their expression of NK
cell receptors, as well as cytokine secretion which is the major function of
these cells. As CD56bright NK cells are highly enriched in tissues and in tumors,
our observations point to a possible effect of local AhR ligands in the
regulation of the function of CD56bright tissue-resident or intratumoral NK
cells.
PMID- 29336032
TI - My mind, your mind, and God's mind: How children and adults conceive of different
agents' moral beliefs.
AB - Extending prior research on belief attributions, we investigated the extent to
which 5- to 8-year-olds and adults distinguish their beliefs and other humans'
beliefs from God's beliefs. In Study 1, children reported that all agents held
the same beliefs, whereas adults drew greater distinctions among agents. For
example, adults reported that God was less likely than humans to view behaviors
as morally acceptable. Study 2 additionally investigated attributions of beliefs
about controversial behaviours (e.g., telling prosocial lies) and belief
stability. These data replicated the main results from Study 1 and additionally
revealed that adults (but not children) reported that God was less likely than
any other agent to think that controversial behaviours were morally acceptable.
Furthermore, across ages, participants reported that another person's beliefs
were more likely to change than either God's beliefs or their own beliefs. We
discuss implications for theories regarding belief attributions and for religious
and moral cognition. Statement of contribution What is already known on this
subject Preschoolers can attribute different beliefs to different humans Children
and adults attribute greater cognitive capacities to God than to humans What the
present study adds Children attribute the same moral beliefs to God and humans
Adults distinguish among different agents' minds when attributing moral beliefs
Developmental differences are less pronounced in judgements of belief stability.
PMID- 29336031
TI - Experiences of case management with chronic illnesses: a qualitative systematic
review.
AB - AIM: This qualitative systematic review aimed to identify and synthesize recent
qualitative studies to improve understanding of the experiences and perceptions
of case management interventions that individuals with chronic illnesses and
their caregivers have. BACKGROUND/INTRODUCTION: Case management has been shown to
be effective at improving quality of care and lowering costs for individuals with
chronic illnesses. However, no qualitative review has been synthesized with
recent qualitative studies about case management experiences by individual with
chronic illnesses. METHODS: This qualitative systematic review uses a thematic
synthesis method to review 10 qualitative studies published within the last 10
years, from 2007 to 2016, thereby identifying and discussing the understandings
that individuals with chronic illnesses and their caregivers have about case
management. RESULTS: From this synthesis, three themes were identified as
facilitators of case management (access to healthcare resources, health status
supports and emotional aid) and two themes were identified as barriers to it (low
information about case management and time constraints). CONCLUSIONS: This is the
first qualitative systematic review of the perceptions and experiences that
individuals with chronic illnesses and their caregivers have about case
management. The facilitators of case management can be employed to inform
patients about the benefits of case management and to improve population health.
IMPLICATIONS FOR NURSING AND HEALTH POLICY: The findings about barriers to case
management can be used to reform case management for populations with chronic
illnesses. These factors should be considered by nursing researchers and
healthcare policymakers when implementing case management.
PMID- 29336033
TI - H2 O2 mediates nitrate-induced iron chlorosis by regulating iron homeostasis in
rice.
AB - The uptake of nitrate by plant roots causes a pH increment in rhizosphere and
leads to iron (Fe) deficiency in rice. However, little is known about the
mechanism how the nitrate uptake-induced high rhizosphere pH causes Fe
deficiency. Here, we found that rice showed severe leaf chlorosis and large
amounts of Fe plaque were aggregated on the root surface and intercellular space
outside the exodermis in a form of ferrihydrite under alkaline conditions. In
this case, there was significantly decreased Fe concentration in shoots, and the
Fe deficiency responsive genes were strongly induced in the roots. The high
rhizosphere pH induced excess hydrogen peroxide (H2 O2 ) production in the
epidermis due to the increasing expression of NADPH-oxidase respiratory burst
oxidase homolog 1, which enhanced root oxidation ability and improved the Fe
plaque formation in rhizosphere. Further, the concentrated H2 O2 regulated the
phenylpropanoid metabolism with increased lignin biosynthesis and decreased
phenolics secretion, which blocked apoplast Fe mobilization efficiency. These
factors coordinately repressed the Fe utilization in rhizosphere and led to Fe
deficiency in rice under high pH. In conclusion, our results demonstrate that
nitrate uptake-induced rhizosphere alkalization led to Fe deficiency in rice,
through H2 O2 -dependent manners of root oxidation ability and phenylpropanoid
metabolism.
PMID- 29336035
TI - Jim's View: "Some Thoughts for Young Scientists".
PMID- 29336034
TI - Quantitative evaluation of collagen and elastic fibers after intense pulsed light
treatment of mouse skin.
AB - BACKGROUND AND OBJECTIVE: The aging of human skin includes intrinsic aging and
photo-aging, which are characterized by a decrease in collagen and the deposition
of abnormal elastic fibers. Intense pulsed light (IPL) sources are widely used in
medicine to treat various cosmetic problems, including photo-damaged skin. Few
studies have examined the microscopic changes produced by IPL. The objective of
this study was to quantitatively evaluate the effects of IPL on collagen and
elastic fibers in mice. MATERIALS AND METHODS: Forty female BALB/c mice were
divided into four subgroups. Group 1 was the control group (n = 10), and groups
2, 3, and 4 were treatment groups (n = 10 in each group). Group 2 received one
treatment, group 3 received two treatments, and group 4 received three treatments
every 2 weeks. Skin tissue was obtained from irradiated areas 24 hours after the
last treatment in each mouse. Collagen fibers were identified using the
picrosirius red method. Elastic fibers were marked by Weigert-oxone stain. All
samples were analyzed and quantified by a light microscope using analyzer system
images. RESULTS: Group 4, which received three IPL treatments, showed significant
quantitative increases in both collagen fibers (P < 0.05) and elastic fibers (P <
0.01). Collagen fibers demonstrated a better parallel distribution in relation to
the epidermis. CONCLUSION: IPL treatment significantly increased the number of
collagen and elastic fibers within the dermis and improved the parallel
distribution of collagen fibers in relation to the epidermis. These results were
evident after three IPL treatments. Lasers Surg. Med. (c) 2018 Wiley Periodicals,
Inc.
PMID- 29336037
TI - Developmental control of hypoxia during bud burst in grapevine.
AB - Dormant or quiescent buds of woody perennials are often dense and in the case of
grapevine (Vitis vinifera L.) have a low tissue oxygen status. The precise timing
of the decision to resume growth is difficult to predict, but once committed, the
increase in tissue oxygen status is rapid and developmentally regulated. Here, we
show that more than a third of the grapevine homologues of widely conserved
hypoxia-responsive genes and nearly a fifth of all grapevine genes possessing a
plant hypoxia-responsive promoter element were differentially regulated during
bud burst, in apparent harmony with resumption of meristem identity and cell
cycle gene regulation. We then investigated the molecular and biochemical
properties of the grapevine ERF-VII homologues, which in other species are oxygen
labile and function in transcriptional regulation of hypoxia-responsive genes.
Each of the 3 VvERF-VIIs were substrates for oxygen-dependent proteolysis in
vitro, as a function of the N-terminal cysteine. Collectively, these data support
an important developmental function of oxygen-dependent signalling in determining
the timing and effective coordination bud burst in grapevine. In addition, novel
regulators, including GASA-, TCP-, MYB3R-, PLT-, and WUS-like transcription
factors, were identified as hallmarks of the orderly and functional resumption of
growth following quiescence in buds.
PMID- 29336036
TI - The incidence and significance of periictal apnea in epileptic seizures.
AB - OBJECTIVE: The aim of this study was to investigate periictal central apnea as a
seizure semiological feature, its localizing value, and possible relationship
with sudden unexpected death in epilepsy (SUDEP) pathomechanisms. METHODS: We
prospectively studied polygraphic physiological responses, including inductance
plethysmography, peripheral capillary oxygen saturation (SpO2 ),
electrocardiography, and video electroencephalography (VEEG) in 473 patients in a
multicenter study of SUDEP. Seizures were classified according to the
International League Against Epilepsy (ILAE) 2017 seizure classification based on
the most prominent clinical signs during VEEG. The putative epileptogenic zone
was defined based on clinical history, seizure semiology, neuroimaging, and EEG.
RESULTS: Complete datasets were available in 126 patients in 312 seizures. Ictal
central apnea (ICA) occurred exclusively in focal epilepsy (51/109 patients [47%]
and 103/312 seizures [36.5%]) (P < .001). ICA was the only clinical manifestation
in 16/103 (16.5%) seizures, and preceded EEG seizure onset by 8 +/- 4.9 s, in
56/103 (54.3%) seizures. ICA >=60 s was associated with severe hypoxemia (SpO2
<75%). Focal onset impaired awareness (FOIA) motor onset with automatisms and FOA
nonmotor onset semiologies were associated with ICA presence (P < .001), ICA
duration (P = .002), and moderate/severe hypoxemia (P = .04). Temporal lobe
epilepsy was highly associated with ICA in comparison to extratemporal epilepsy
(P = .001) and frontal lobe epilepsy (P = .001). Isolated postictal central apnea
was not seen; in 3/103 seizures (3%), ICA persisted into the postictal period.
SIGNIFICANCE: ICA is a frequent, self-limiting semiological feature of focal
epilepsy, often starting before surface EEG onset, and may be the only clinical
manifestation of focal seizures. However, prolonged ICA (>=60 s) is associated
with severe hypoxemia and may be a potential SUDEP biomarker. ICA is more
frequently seen in temporal than extratemporal seizures, and in typical temporal
seizure semiologies. ICA rarely persists after seizure end. ICA agnosia is
typical, and thus it may remain unrecognized without polygraphic measurements
that include breathing parameters.
PMID- 29336038
TI - A single-nucleotide polymorphism in the canine cytochrome b5 reductase (CYB5R3)
gene is associated with sulfonamide hypersensitivity and is overrepresented in
Doberman Pinschers.
AB - Canine sulfonamide hypersensitivity (HS) has been associated with a variant in
the cytochrome b5 reductase gene (CYB5R3 729A>G), which encodes a drug
detoxifying enzyme. Study objectives were to determine variant allele frequency
in Doberman Pinschers (DOBE), a breed which may be predisposed to sulfonamide HS,
and to characterize the effects of CYB5R3 729G on gene expression and function.
CYB5R3 729A>G allele frequencies were compared between DOBE (n = 24) vs. non
Doberman (non-DOBE; n = 60) dogs. CYB5R3mRNA expression, protein expression, and
reduction of sulfamethoxazole hydroxylamine were compared between banked canine
liver samples of 729AA vs. GG genotype. The 729G allele was overrepresented in
DOBE (1.00) vs. non-DOBE dogs (0.567, p < .0001). mRNA and protein expressions as
well as cyt b5 reductase activity were similar between livers of AA and GG
genotype. All Doberman Pinschers in this study were homozygous for CYB5R3 729G,
which could contribute to this breed's apparent predisposition to sulfonamide HS.
However, CYB5R3 729G does not alter sulfamethoxazole detoxification capacity, so
a direct role could not be demonstrated. It is possible that this marker is
linked to another contributing variant.
PMID- 29336039
TI - Pollen germination and in vivo fertilization in response to high-temperature
during flowering in hybrid and inbred rice.
AB - High-temperature during flowering in rice causes spikelet sterility and is a
major threat to rice productivity in tropical and subtropical regions, where
hybrid rice development is increasingly contributing to sustain food security.
However, the sensitivity of hybrids to increasing temperature and physiological
responses in terms of dynamic fertilization processes is unknown. To address
these questions, several promising hybrids and inbreds were exposed to control
temperature and high day-time temperature (HDT) in Experiment 1, and hybrids
having contrasting heat tolerance were selected for Experiment 2 for further
physiological investigation under HDT and high-night-time-temperature treatments.
The day-time temperature played a dominant role in determining spikelet fertility
compared with the night-time temperature. HDT significantly induced spikelet
sterility in tested hybrids, and hybrids had higher heat susceptibility than the
high-yielding inbred varieties. Poor pollen germination was strongly associated
with sterility under high-temperature. Our novel observations capturing the
series of dynamic fertilization processes demonstrated that pollen tubes not
reaching the viable embryo sac was the major cause for spikelet sterility under
heat exposure. Our findings highlight the urgent need to improve heat tolerance
in hybrids and incorporating early-morning flowering as a promising trait for
mitigating HDT stress impact at flowering.
PMID- 29336040
TI - Evaluation of reference values of standard semen parameters in fertile Egyptian
men.
AB - The reference values of human semen, published in the WHO's latest edition in
2010, were lower than those previously reported. The objective of this study was
to evaluate reference values of standard semen parameters in fertile Egyptian
men. This cross-sectional study included 240 fertile men. Men were considered
fertile when their wives had recent spontaneous pregnancies with time to
pregnancy (TTP) <=12 months. The mean age of fertile men was 33.8 +/- 0.5 years
(range 20-55 years). The 5th percentiles (95% confidence interval) of macroscopic
semen parameters were 1.5 ml for volume and 7.2 for pH. The 5th percentiles of
microscopic parameters were 15 million/ml for sperm concentration, 30 million per
ejaculate for total sperm count, 50% for total motility, 40% for progressive
motility, 62% for vitality, 4% for normal sperm forms and 0.1 million/ml for
seminal leucocyte counts. In conclusion, fertile Egyptian men had higher
reference values of sperm total motility, progressive motility and vitality, and
lower reference values for total sperm counts as compared to those determined by
the latest edition of the WHO laboratory manual in 2010. Other semen parameters
were identical to those defined by the WHO 2010 manual.
PMID- 29336041
TI - Symptoms of social anxiety, depression, and stress in parents of children with
social anxiety disorder.
AB - OBJECTIVES: It has been suggested that elevated maternal social anxiety may play
a disorder-specific role in maintaining childhood social anxiety disorder (SAD),
but few studies have examined whether mothers of children with SAD are more
socially anxious than mothers of children with other anxiety disorders (ANX).
This study set out to examine whether symptoms of social anxiety were more severe
amongst mothers of 7-12 year old children presenting for treatment with SAD (n =
260) compared to those presenting with ANX (n = 138). In addition, we examined
whether there were differences between these two groups in terms of maternal and
paternal general anxiety, depression, and stress. METHOD: Parents of 7-12 year
old children referred for treatment of SAD or ANX completed self-report
questionnaire measures of emotional symptoms. RESULTS: Compared to mothers of
children with ANX, mothers of children with SAD reported significantly higher
levels of social anxiety, general anxiety, and depression. In addition, fathers
of children with SAD reported significantly higher levels of anxiety, stress, and
depression than fathers of children with ANX. CONCLUSIONS: This study is one of
the few existing studies that have examined mothers' and fathers' psychopathology
across different childhood anxiety disorders. Compared to parents of children
with ANX, parents of children with SAD may have poorer mental health which may
inhibit optimum child treatment outcomes for children with SAD. Thus, targeting
parental psychopathology may be particularly important in the treatment of
childhood SAD. PRACTITIONER POINTS: Consideration of parental psychopathology may
be particularly important in the treatment of childhood social anxiety disorder.
Mothers of children with social anxiety disorder are more socially anxious than
mothers of children with other anxiety disorders Fathers of children with social
anxiety disorder are more anxious and depressed than fathers of children with
other anxiety disorders Participants were predominantly of high socioeconomic
status. Parental diagnostic information was not obtained.
PMID- 29336042
TI - Forum for the History of the Human Sciences.
PMID- 29336043
TI - 2017 Cheiron Young Scholar Award Winner: Shayna Fox Lee.
PMID- 29336044
TI - ESHHS 2018, GRONINGEN (NL) - First call for abstracts.
PMID- 29336045
TI - The creation of a postcolonial subject: The Chicago and Ateneo de Manila schools
and the Peace Corps in the Philippines, 1960-1970.
AB - In the 1950s and 1960s scholars from the University of Chicago and the Ateneo de
Manila created social scientific knowledge that helped establish the Peace Corps
as a Cold War institution in the Philippines. Central were the social scientists
at the University of Chicago and the Ateneo de Manila University who established
a knowable postcolonial subject: "the Filipino," which resulted from their
research on Philippine values. In this context, the Ateneo/Chicago social
scientists developed the "SIR," the "smooth interpersonal relation" model that
entails the notion that Filipinos and Filipinas particularly valued this
nonconfrontational skill set among people. The SIR model was taught by social
science experts to early Peace Corps volunteers as they prepared for their
assignments in the Philippines. The article shows how the SIR model could cause
distress and confusion as it was applied by Peace Corps volunteers in the
Philippines.
PMID- 29336046
TI - News and Notes: Conferences.
PMID- 29336047
TI - Acrodermatitis acidaemica.
AB - Methylmalonic acidaemia (MMA) is an inborn error of amino acid metabolism that
may be associated with cutaneous manifestations mimicking other diagnoses,
including staphylococcal scalded skin syndrome (SSSS), psoriasis and
acrodermatitis enteropathica. Whether this is due to the underlying metabolic
disorder itself or occurs as a consequence of dietary restriction has yet to be
elucidated. Skin biopsies typically show histological features shared by a number
of other metabolic disorders and nutritional deficiency-associated diseases. Some
presentations, especially SSSS-like eruptions, may be associated with acute
metabolic decompensation. An underlying metabolic disorder, such as MMA, should
be considered in a diagnosed adult or undiagnosed child presenting with skin
eruptions that resemble those listed above, so that specialist management may be
initiated early.
PMID- 29336048
TI - Fetal growth: too little or just right?
PMID- 29336049
TI - A distinct group of north European Aedes vexans as determined by mitochondrial
and nuclear markers.
AB - The floodwater mosquito Aedes (Aedimorphus) vexans (Meigen, 1830) (Diptera:
Culicidae) is common in several areas of Sweden and is predicted to become more
abundant in the wake of expected changes in precipitation and temperature caused
by climate change. As well as being a nuisance, Ae. vexans can act as a vector of
over 30 viruses. In the event of an outbreak of disease caused by a vector-borne
virus, knowledge of the distribution, population structure and intermixing of
populations from different locations will help direct resources to target
locations to prevent spread of the pathogen. The present study analysed
individual Ae. vexans from eight locations throughout Sweden. Based on the
mitochondrial cytochrome oxidase I (COI) marker, a subset of the analysed
mosquitoes cluster apart from the other samples. Similarly, two nuclear loci were
sequenced and the same phylogenetic structure observed. These results indicate
that this group represents a reproductively isolated population among Ae. vexans.
Comparisons with COI sequences held in the Barcode of Life Database (BoLD) for
Ae. vexans from around the world show that specimens collected in Belgium and
Estonia group together with the Swedish group, suggesting that this genotype is
present throughout northern Europe. These results suggest there is a cryptic
taxonomic unit related to Ae. vexans in northern Europe.
PMID- 29336050
TI - Sperm fluorescent in situ hybridisation study of interchromosomal effect in six
Tunisian carriers of reciprocal and Robertsonian translocations.
AB - Carriers of structural chromosomal anomalies, translocations and inversions are
at increased risk of aneuploid gametes production. Besides the direct effect on
the involved chromosomes, these rearrangements might disturb the segregation of
other structurally normal chromosomes during meiosis. Such event is known as
interchromosomal effect. In this study, six male carriers of translocations, four
reciprocals and two Robertsonians, were investigated. In addition, seven fertile
men with normal 46,XY karyotypes and normal sperm characteristics were enrolled
as a control group. Spermatic fluorescent in situ hybridisation specific for
chromosomes X, Y, 18, 21 and 22 was carried out. The Mann-Whitney U-test was used
to compare the aneuploidy rates between patients and controls. All translocation
carriers showed significantly increased frequencies of disomy of all investigated
chromosomes, and diploid gametes compared with the control group (p < .05).
However, disomy XY was not significantly different between controls and patients
(p > .05). We have also observed a considerable interindividual variability in
disomy and diploidy rates. These results confirm that the interchromosomal effect
seems to exist and could contribute to higher rates of abnormal prenatal
aneuploidy, resulting in a small increase in the risk of miscarriage and birth of
children with congenital abnormalities and a potential reduction in fertility.
PMID- 29336051
TI - Right testicular volume is a dominant predictor of testicular function determined
by sperm parameters and total testosterone.
AB - This study aims to evaluate the predictive value of left testicular volume (LTV)
and right testicular volume (RTV) for testicular function respectively. Men who
requested fertility testing for any reason were enrolled from December 2012 to
November 2015. Subjects with primary scrotal diseases or a condition interfering
reproductive system were excluded. Testicular volume (TV) was evaluated by
scrotal ultrasound. Sex hormone and semen analysis including sperm concentration
(SC) and sperm motility rate (SMR) were performed. Statistical analysis including
comparison, stepwise linear regression and logistic regression was used. Two
hundred and seventy-four patients with oligoasthenozoospermia/low testosterone
and 27 control subjects were enrolled. Both LTV and RTV positively correlated
with testicular function, and no differences were found between bilateral TV. RTV
is the best independent factor associated with testicular function determined by
SC (beta=.292, p < .001), SMR (beta=.227, p < .001) and total testosterone (TT)
(beta=.245, p < .001). Using a RTV value of 15.47 ml, the highest discriminating
sensitivity and specificity were 66.7% and 62.4% respectively. RTV (<15 ml) was
the only positive predictor for low testicular function (odds ratio=2.79, 95%
confidence interval: 1.18-6.66; p =.020). RTV rather than LTV is the independent
factor of overall testicular function determined by semen quality and TT levels.
Further studies are needed to support and elucidate the difference in volume
function between bilateral testes.
PMID- 29336052
TI - Rapidly developing heart failure from capecitabine cardiotoxicity: a case study.
PMID- 29336053
TI - Specific Modulation of Vertebral Marrow Adipose Tissue by Physical Activity.
AB - Marrow adipose tissue (MAT) accumulation with normal aging impacts the bone,
hemopoiesis, and metabolic pathways. We investigated whether exercise was
associated with lower MAT, as measured by vertebral marrow fat fraction (VFF) on
magnetic resonance imaging. A total of 101 healthy individuals (54 females) aged
25 to 35 years without spine or bone disease but with distinct exercise histories
were studied. Long-distance runners (67 km/wk, n = 25) exhibited lower mean
lumbar VFF (27.9% [8.6%] versus 33.5% [6.0%]; p = 0.0048) than non-sporting
referents (n = 24). In habitual joggers (28 km/wk, n = 30), mean lumbar VFF was
31.3% (9.0%) (p = 0.22 versus referents) and 6.0 percentage points lower than
referents at vertebrae T10 , T11 , and T12 (p <= 0.023). High-volume road cycling
(275 km/wk, n = 22) did not impact VFF. 3D accelerations corresponding to faster
walking, slow jogging, and high-impact activities correlated with lower VFF,
whereas low-impact activities and sedentary time correlated with higher mean
lumbar VFF (all p <= 0.05). Given an estimated adipose bone marrow conversion of
7% per decade of life, long distance runners, with 5.6 percentage points lower
VFF, showed an estimated 8-year younger vertebral marrow adipose tissue
phenotype. Regression analysis showed a 0.7 percentage point reduction in mean
lumbar VFF with every 9.4 km/wk run (p = 0.002). This study presents the first
evidence in humans or animals that specific volumes and types of exercise may
influence the age-determined adipose marrow conversion and result in low MAT.
These results identify a potentially modifiable risk factor for prevalent chronic
conditions related to bone metabolism, hemopoietic production, and other
metabolic functions with potential global health applications. (c) 2017 American
Society for Bone and Mineral Research.
PMID- 29336055
TI - Intrauterine ritodrine exposure and childhood asthma: Is ritodrine a real
culprit?
PMID- 29336054
TI - The EAACI/GA2LEN/EDF/WAO guideline for the definition, classification, diagnosis
and management of urticaria.
AB - This evidence- and consensus-based guideline was developed following the methods
recommended by Cochrane and the Grading of Recommendations Assessment,
Development and Evaluation (GRADE) working group. The conference was held on 1
December 2016. It is a joint initiative of the Dermatology Section of the
European Academy of Allergology and Clinical Immunology (EAACI), the EU-founded
network of excellence, the Global Allergy and Asthma European Network (GA2LEN),
the European Dermatology Forum (EDF) and the World Allergy Organization (WAO)
with the participation of 48 delegates of 42 national and international
societies. This guideline was acknowledged and accepted by the European Union of
Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease,
presenting with wheals, angioedema, or both. The lifetime prevalence for acute
urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic
forms of urticaria are disabling, impair quality of life and affect performance
at work and school. This guideline covers the definition and classification of
urticaria, taking into account the recent progress in identifying its causes,
eliciting factors and pathomechanisms. In addition, it outlines evidence-based
diagnostic and therapeutic approaches for the different subtypes of urticaria.
PMID- 29336056
TI - ILEI is an important intermediate participating in the formation of TGF-beta1
induced renal tubular EMT.
AB - : Renal interstitial fibrosis is the most common process by which chronic kidney
diseases progress to end-stage renal failure. Epithelial-to-mesenchymal
transitions (EMTs) play a crucial role in the progression of renal interstitial
fibrosis. A newly identified cytokine, interleukin-like EMT inducer (ILEI), has
been linked to EMT in some diseases. However, the effects of ILEI on renal
tubular EMT have not yet been well established. Here, we characterize the
expression of ILEI in tubular EMT and describe the role and mechanism of ILEI in
transforming growth factor beta 1 (TGF-beta1)-induced renal tubular EMT. The
results indicate that ILEI is involved in renal tubular EMT induced by TGF-beta1,
as overexpression of ILEI not only induces EMT of HK-2 cells independently but
also profoundly enhances EMT in response to TGF-beta1. Supporting this finding,
ILEI small interfering RNA was found to block the EMT of HK-2 cells induced by
TGF-beta1. This work additionally suggests ILEI mediates TGF-beta1-dependent EMT
via the extracellular regulated protein kinases (ERKs) and protein kinase B (Akt)
signalling pathways. In conclusion, ILEI appears to play a crucial role in
mediating TGF-beta1-induced EMT through the Akt and ERK pathways, which may
provide a therapeutic target for the treatment of fibrotic kidney diseases.
SIGNIFICANCE OF THE STUDY: There is no study reporting the effect of ILEI in
renal EMTs. In this research, we examined the role and mechanism of ILEI in EMT
using tubular epithelial cell; we found that ILEI participated in renal tubular
EMT, and overexpression of ILEI can not only induce EMT of HK-2 cells
independently but also enhance EMT in response to TGF-beta1. Meanwhile, we found
ILEI small interfering RNA blocked the EMT induced by TGF-beta1, and ILEI
participates in the EMT caused by TGF-beta1 via ERK and Akt signalling pathways.
We hoped to provide new ideas in further study on the prevention and treatment of
fibrotic kidney diseases.
PMID- 29336057
TI - Amelioration of colitis through blocking lymphocytes entry to Peyer's patches by
sphingosine-1-phosphate lyase inhibitor.
AB - BACKGROUND AND AIM: Sphingosine-1-phosphate (S1P) receptor 1, a therapeutic
target of the S1P1 agonist FTY720, plays a crucial role in lymphocyte migration
and is expressed in several cells including naive T lymphocytes and endothelial
cells. 2-Acetyl-4-tetrahydroxybutyl imidazole (THI), an inhibitor of S1P lyase,
exhibits immunomodulatory activity through increasing the S1P concentration in
the secondary lymphoid organs, but its effects on colitis remain unclear. This
study aimed to clarify how THI affects colitis and migration of naive T
lymphocytes in Peyer's patches (PPs). METHODS: The effect of THI on gut immunity
was investigated by analyzing the dextran sulfate sodium (DSS)-induced murine
colitis model, lymphocyte components in thoracic duct lymphocytes (TDLs), and
microscopic movement of TDLs in PPs. RESULTS: 2-Acetyl-4-tetrahydroxybutyl
imidazole ameliorated DSS-induced colitis histologically by causing a significant
decrease in colonic lymphocyte infiltration and expression of mucosal pro
inflammatory cytokines. THI suppressed the inflow of naive T lymphocytes into the
thoracic duct. Microscopic observation of PPs in control animals revealed that
many TDLs egressed to the stroma and migrated to lymph capillaries after
attaching to the high endothelial venules (HEVs). THI or FTY720 treatment in
recipient animals blocked lymphocyte egression from the HEVs to the stroma.
CONCLUSIONS: This is the first study to clarify the ameliorating effects of THI
on DSS-induced colitis. Microscopic observations demonstrated the involvement of
HEVs in the egression of S1P-dependent gut-tropic T lymphocytes to lymph
capillaries. This S1P lyase inhibitor might become a novel immunosuppressant for
inflammatory bowel disease therapy by blocking infiltration of lymphocytes
through HEVs into the stroma in PPs.
PMID- 29336058
TI - Programming settings and recharge interval in a prospective study of a
rechargeable sacral neuromodulation system for the treatment of overactive
bladder.
AB - AIMS: The RELAX-OAB study is designed to confirm the safety, efficacy, and
technical performance of the Axonics r-SNM System, a miniaturized, rechargeable
SNM system approved in Europe and Canada for the treatment of bladder and bowel
dysfunction. The purpose of this article is to describe study subjects' ability
to charge the rechargeable neurostimulator and to document their neurostimulator
program settings and recharge interval over time. METHODS: Fifty-one OAB patients
were implanted in a single-stage procedure. These results represent the 3-month
charging experience for 48 subjects who completed the 3-month follow-up. Recharge
intervals were estimated using therapy stimulation settings and subject
experience was evaluated using questionnaires. RESULTS: Forty-seven of forty
eight (98%) subjects were able to successfully charge their device prior to
follow-up within 1-month post-implant. At 3-month post-implant, 98% of subjects
were able to charge prior to their follow-up visit. Average stimulation amplitude
across all subjects was 1.8 mA (+/-1.1 mA). A total of 69% of subjects had >=14
day recharge intervals (time between charging) and 98% of subjects had >=7-day
recharge interval. No charging related adverse events occurred. CONCLUSIONS:
Study subjects were able to charge the Axonics r-SNM System and stimulation
settings provided 2 weeks of therapy between recharging for most subjects.
Subject satisfaction indicates that subjects are satisfied with rechargeable SNM
therapy.
PMID- 29336059
TI - Erratum for Ann. N.Y. Acad. Sci. Volume 1299: v-x.
PMID- 29336060
TI - What the non-nephrologist needs to know about dialysis.
AB - The End-Stage Renal Disease (ESRD) program now serves approximately 675,000
individuals in the United States at a cost of $26.1 billion to the Medicare
system. Given the size of this population, healthcare providers from all
disciplines will deliver care to patients on dialysis. Mortality remains high
among patients on chronic dialysis, with 42.3% surviving 5 years. As this is a
vulnerable population, it is important in the care of ESRD patients that non
nephrologists have a working knowledge of issues germane to dialysis. This review
examines the physiology, mechanics, complications, and care delivery concerns of
kidney dialysis modalities relevant to the non-nephrologist. The majority of
patients receive in-center hemodialysis thrice weekly, with a small proportion on
home-based therapies such as peritoneal dialysis or home hemodialysis. Inpatients
may undergo hemodialysis or peritoneal dialysis, and in critically ill patients,
continuous renal replacement therapies are utilized. Practical aspects of each of
these modalities are discussed.
PMID- 29336061
TI - Classifying High-risk Children Born Preterm.
PMID- 29336062
TI - Time-Varying Effects of Signs and Symptoms on Pregnancy Loss <20 Weeks: Findings
from a Preconception Prospective Cohort Study.
AB - BACKGROUND: Although pregnancy loss affects one-third of pregnancies, the
associated signs/symptoms have not been fully described. Given the dynamic nature
of maternal physiologic adaptation to early pregnancy, we posited the
relationships between signs/symptoms and subsequent loss would vary weekly.
METHODS: In a preconception cohort with daily follow-up, pregnancies were
ascertained by self-administered sensitive home pregnancy tests on day of
expected menses. We evaluated the effects of weekly time-varying signs/symptoms
(including vaginal bleeding, lower abdominal cramping, and nausea and/or
vomiting) on pregnancy loss <20 weeks in Cox proportional hazards models and
calculated the week-specific probability of loss by the presence/absence of each
sign/symptom. RESULTS: Of 341 pregnancies ascertained by home pregnancy test, 95
(28%) ended in loss. Relationships between signs/symptoms and loss varied across
time since first positive pregnancy test. In the first week following pregnancy
confirmation, when many losses occurred, bleeding [hazard ratio (HR) 8.7, 95%
confidence interval (CI) 4.7, 16.0] and cramping (HR 1.8, 95% CI 1.2, 2.7) were
associated with loss even when accompanied by nausea and/or vomiting (HR 5.2, 95%
CI 2.6, 10.5). After the second week, new relationships emerged with nausea
and/or vomiting inversely associated (HR range 0.6-0.3, all 95% CI upper bounds
<1.00) and bleeding no longer associated with loss. Probabilities of loss of
ranged from 78% (95% CI 59%, 96%) with bleeding present in week 1 to 8% (95% CI
5%, 12%) with nausea/vomiting present in week 5. CONCLUSIONS: Relationships
between signs/symptoms and pregnancy loss vary in early pregnancy possibly
reflecting maternal physiologic response.
PMID- 29336063
TI - Use of complementary and alternative medicine in children with asthma.
PMID- 29336064
TI - Home hemodialysis education during postdoctoral training: Challenges and
innovations.
AB - Inadequate education in home hemodialysis (HHD) fellowship training might
contribute to underutilization of this modality in the United States. Most
graduates of nephrology fellowships do not grade themselves as competent in HHD
suggesting that fellowship training in HHD is inadequate. An essential component
for fellow education is at least one faculty member with expertise in HHD who is
passionate about promoting the use of this modality. At a minimum, fellow
training should utilize a curriculum that includes both lectures about HHD and
outpatient clinical exposure to this modality over a period of at least 6-12
months. Fellows benefit from the opportunity to transition at least three
patients to a home modality to gain experience with modality education, access
placement, initial prescriptions, and home dialysis training. They should spend
time with HHD training nurses to learn more about modality education, observe
nurse intake interviews with patients in order to learn the criteria for entrance
into the home dialysis program as well as recognize how to identify potential
barriers to successful home dialysis therapy. To expose fellows to problems that
do not occur during clinic visits fellows are encouraged to take first call
during the day for HHD patients. There are many opportunities to do research and
quality improvement projects which might also propel some fellows into an
academic career as a home dialysis nephrologist.
PMID- 29336065
TI - Optimization of 18 F-syntheses using 19 F-reagents at tracer-level concentrations
and liquid chromatography/tandem mass spectrometry analysis: Improved synthesis
of [18 F]MDL100907.
AB - Traditional radiosynthetic optimization faces the challenges of high radiation
exposure, cost, and inability to perform serial reactions due to tracer decay. To
accelerate tracer development, we have developed a strategy to simulate
radioactive 18 F-syntheses by using tracer-level (nanomolar) non-radioactive 19 F
reagents and LC-MS/MS analysis. The methodology was validated with fallypride
synthesis under tracer-level 19 F-conditions, which showed reproducible and
comparable results with radiosynthesis, and proved the feasibility of this
process. Using this approach, the synthesis of [18 F]MDL100907 was optimized
under 19 F-conditions with greatly improved yield. The best conditions were
successfully transferred to radiosynthesis. A radiochemical yield of 19% to 22%
was achieved with the radiochemical purity >99% and the molar activity 38.8 to
53.6 GBq/ MUmol (n = 3). The tracer-level 19 F-approach provides a high
throughput and cost-effective process to optimize radiosynthesis with reduced
radiation exposure. This new method allows medicinal and synthetic chemists to
optimize radiolabeling conditions without the need to use radioactivity.
PMID- 29336066
TI - Medication use and association with urinary incontinence in women: Data from the
Norwegian Prescription Database and the HUNT study.
AB - AIMS: To investigate the association between medication use and urinary
incontinence (UI) in women. METHODS: In a cross-sectional population-based study
we analyzed questionnaire data on UI, including type and severity, from 21 735
women included in the Nord-Trondelag Health Study (HUNT) in Norway. These data
were linked to data on filled prescriptions retrieved from the Norwegian
Prescription Database. A multivariate logistic regression model was used to
calculate the odds for having UI related to the number of filled prescriptions
for selected drug groups during the 6 months prior to participation in HUNT,
after adjustment for numerous confounding factors. RESULTS: Significant
associations with UI were found for selective serotonin reuptake inhibitors
(SSRIs) and lamotrigine with OR 1.52 (1.30-1.78) and 2.73 (1.59-4.68) for two or
more filled prescriptions. Both for SSRIs and lamotrigine, the associations were
pronounced for mixed UI, whereas there were no clear-cut increased risk of stress
UI and urgency UI. The relations were strongest in women with the most severe
symptoms. One filled prescription of antipsychotics, but not two or more, was
also found to be related to UI with OR 1.91 (1.35-2.71). No associations were
found for benzodiazepines, zopiclone/zolpidem, beta blockers, and diuretics.
CONCLUSIONS: The odds for having UI were found to be about 1.5-fold in women
using SSRIs and almost threefold in women using lamotrigine. The association with
lamotrigine has not been reported previously, and should be further evaluated in
future studies.
PMID- 29336068
TI - Isatin, an endogenous nonpeptide biofactor: A review of its molecular targets,
mechanisms of actions, and their biomedical implications.
AB - Isatin (indole-2,3-dione) is an oxidized indole. It is widely distributed in
mammalian tissues and body fluids, where isatin concentrations vary significantly
from <0.1 to > 10 uM. Isatin output is increased under conditions of stress.
Exogenously administered isatin is characterized by low toxicity, mutagenicity,
and genotoxicity in vivo. Cytotoxic effects of isatin on various cell cultures
are usually observed at concentrations exceeding 100 uM. Binding of [3 H]isatin
to rat brain sections is consistent with its physiological concentrations.
Proteomic analysis of mouse and rat brain isatin-binding proteins revealed about
90 individual proteins, which demonstrated significant interspecies differences
(rat versus mouse). Certain evidence exist that redox state(s) and possibly other
types of posttranslational modifications regulate affinity of target proteins to
isatin. Recent data suggest that interacting with numerous intracellular isatin
binding proteins, isatin can act as a regulator of complex protein networks in
norm and pathology. Physiological concentrations of isatin in vitro inhibit
monoamine oxidase B and natriuretic peptide receptor guanylate cyclase, higher
(neuroprotective) concentrations (50-400 MUM) cause apoptosis of various
(including malignant tumor) cell lines and influence expression of certain
apoptosis-related genes. Being administered in vivo, isatin exhibits various
behavioral effects; it attenuates manifestations of MPTP-induced parkinsonism and
tumor growth in experimental animal models. (c) 2017 BioFactors, 44(2):95-108,
2018.
PMID- 29336069
TI - An examination of the interaction between morality and self-control in offending:
A study of differences between girls and boys.
AB - BACKGROUND: There is a well-documented gender difference in offending, with
evidence that boys, on average, are more involved in crime than girls. Opinions
differ, however, on whether the causes of crime apply to girls and boys
similarly. AIMS: Our aim is to explore crime propensity in boys and girls. Our
research questions were (1) are there differences between boys and girls in moral
values and self-control; (2) are these attributes similarly correlated with
offending among girls and boys; and (3) is any interaction effect between
morality and self-control identical for girls and boys. METHODS: Data were drawn
from the Malmo Individual and Neighbourhood Development Study, which includes 481
girls and boys aged 16-17. An 8-item self-control scale was derived from
Grasmick's self-control instrument; we created a 16-item morality scale. Analysis
of variance was used to test for differences in scale scores. RESULTS: There were
significant gender differences in moral values but not self-control. Moral values
and self-control were significantly correlated with offending among both girls
and boys. In the multiple regression analysis, the three-way interaction term
used to test the interaction between gender, self-control and moral values was
non-significant, indicating that the magnitude of the self-control-moral value
interaction is not affected by gender. CONCLUSIONS: Our findings indicate that
effects of morality and self-control are general and apply to girls and boys
similarly, so more research is needed to explain gender differences in crime
prevalence. (c) 2018 The Authors Criminal Behaviour and Mental Health Published
by John Wiley & Sons Ltd.
PMID- 29336070
TI - Changes in surface characteristics of titanium and zirconia after surface
treatment with ultraviolet light or non-thermal plasma.
AB - Positive effects of irradiation with ultraviolet (UV) light or treatment with non
thermal plasma on titanium and zirconia surfaces have been described in various
studies. The aim of this study was to assess and compare the changes in the
physicochemical surface conditions of titanium and zirconia surfaces after a
short treatment with UV light or with non-thermal plasmas of argon or oxygen.
Titanium and zirconia samples with moderately rough surfaces were treated for 12
min either in a UV-light oven or in a non-thermal plasma reactor that generates
non-thermal plasmas of oxygen or argon. Changes in surface conditions were
assessed by confocal microscopy, dynamic contact angle measurement, and X-ray
photoelectron spectroscopy (XPS). No changes in roughness occurred. Ultraviolet
irradiation and non-thermal plasma significantly increased the wettability of the
titanium and zirconia surfaces. X-ray photoelectron spectroscopy showed an
increase of oxygen and a significant decrease of carbon after treatment with
either method. Thus, ultraviolet light and non-thermal plasma were found to be
able to improve the chemical surface conditions of titanium and zirconia
following a short exposure time. However, further in vitro and in vivo studies
are needed to determine the relevance of the results.
PMID- 29336071
TI - Hierarchical N-Rich Carbon Sponge with Excellent Cycling Performance for Lithium
Sulfur Battery at High Rates.
AB - Lithium-sulfur batteries (LSBs) are receiving extensive attention because of
their high theoretical energy density. However, practical applications of LSBs
are still hindered by their rapid capacity decay and short cycle life, especially
at high rates. Herein, a highly N-doped (~13.42 at %) hierarchical carbon sponge
(HNCS) with strong chemical adsorption for lithium polysulfide is fabricated
through a simple sol-gel route followed by carbonization. Upon using the HNCS as
the sulfur host material in the cathode and an HNCS-coated separator, the battery
delivers an excellent cycling stability with high specific capacities of 424 and
326 mA h g-1 and low capacity fading rates of 0.033 % and 0.030 % per cycle after
1000 cycles under high rates of 5 and 10 C, respectively, which are superior to
those of other reported carbonaceous materials. These impressive cycling
performances indicate that such a battery could promote the practical application
prospects of LSBs.
PMID- 29336067
TI - Treatment of allergic rhinitis using mobile technology with real-world data: The
MASK observational pilot study.
AB - BACKGROUND: Large observational implementation studies are needed to triangulate
the findings from randomized control trials as they reflect "real-world" everyday
practice. In a pilot study, we attempted to provide additional and complementary
insights on the real-life treatment of allergic rhinitis (AR) using mobile
technology. METHODS: A mobile phone app (Allergy Diary, freely available in
Google Play and Apple App stores) collects the data of daily visual analog scales
(VAS) for (i) overall allergic symptoms, (ii) nasal, ocular, and asthma symptoms,
(iii) work, as well as (iv) medication use using a treatment scroll list
including all medications (prescribed and over the counter (OTC)) for rhinitis
customized for 15 countries. RESULTS: A total of 2871 users filled in 17 091 days
of VAS in 2015 and 2016. Medications were reported for 9634 days. The assessment
of days appeared to be more informative than the course of the treatment as, in
real life, patients do not necessarily use treatment on a daily basis; rather,
they appear to increase treatment use with the loss of symptom control. The
Allergy Diary allowed differentiation between treatments within or between
classes (intranasal corticosteroid use containing medications and oral H1
antihistamines). The control of days differed between no [best control], single,
or multiple treatments (worst control). CONCLUSIONS: This study confirms the
usefulness of the Allergy Diary in accessing and assessing everyday use and
practice in AR. This pilot observational study uses a very simple assessment
(VAS) on a mobile phone, shows novel findings, and generates new hypotheses.
PMID- 29336072
TI - Re: Re: Karabakan M, Bozkurt A, Hirik E, Celebi B, Akdemir S, Guzel O, Nuhoglu B.
The prevalence of premature ejaculation in young Turkish men. Andrologia 2016;
24: 1-5.
PMID- 29336073
TI - Hypoxia-ischemia and brain injury in infants born preterm.
PMID- 29336074
TI - Closing the knowledge gap in Mexico: towards evidence-based medicine in childhood
disability.
PMID- 29336075
TI - What causes the encephalopathy of prematurity?
PMID- 29336076
TI - Cerebral palsy and genomics: an international consortium.
PMID- 29336077
TI - Perspectives on caring for the child and the caregiver.
PMID- 29336078
TI - The novel Axonics(r) rechargeable sacral neuromodulation system: Procedural and
technical impressions from an initial North American experience.
AB - AIMS: The rechargeable Axonics(r) r-SNMTM System is currently approved and
available in Europe and Canada, with US FDA approval pending. This article
provides a review of the system along with technique and technical considerations
for its implantation based on my clinical experience with the new Axonics r-SNM
System. METHODS: The description of the surgical technique and technological
considerations for the Axonics r-SNM System is based my clinical experience of 11
cases performed at UHN Toronto Western Hospital. RESULTS: While the Axonics
system is intended to provide similar therapy to the existing SNM system, the
Axonics system has several new technological advances. Understanding these
differences and optimizing surgical technique is anticipated to improve outcomes
and patient experience. CONCLUSIONS: Overall the Axonics r-SNM System and implant
procedure requires minimal learning curve for experienced SNM implanters and
provides several enhanced features for physicians and patients. Further
experience by others may elucidate other nuances important to the implantation of
this novel SNM system.
PMID- 29336079
TI - The low FODMAP diet in the management of irritable bowel syndrome: an evidence
based review of FODMAP restriction, reintroduction and personalisation in
clinical practice.
AB - Dietary restriction of fermentable oligosaccharides, disaccharides,
monosaccharides and polyols (FODMAPs) is effective in the management of
functional gastrointestinal symptoms that occur in irritable bowel syndrome
(IBS). Numerous reviews have been published regarding the evidence for their
restriction in the low FODMAP diet; however, few reviews discuss the
implementation of the low FODMAP diet in practice. The aim of this review is to
provide practical guidance on patient assessment and the implementation and
monitoring of the low FODMAP diet. Broadly speaking, the low FODMAP diet consists
of three stages: FODMAP restriction; FODMAP reintroduction; and FODMAP
personalisation. These stages can be covered in at least two dietetic
appointments. The first appointment focuses on confirmation of diagnosis,
comprehensive symptom and dietary assessment, detailed description of FODMAPs and
their association with symptom induction, followed by counselling regarding
FODMAP restriction. Dietary counselling should be tailored to individual needs
and appropriate resources provided. At the second appointment, symptoms and diet
are re-assessed and, if restriction has successfully reduced IBS symptoms,
education is provided on FODMAP reintroduction to identify foods triggering
symptoms. Following this, the patient can follow FODMAP personalisation for which
a less restrictive diet is consumed that excludes their personal FODMAP triggers
and enables a more diverse dietary intake. This review provides evidence and
practice guidance to assist in delivering high-quality clinical service in
relation to the low FODMAP diet.
PMID- 29336080
TI - Special issues for a special community.
PMID- 29336081
TI - Measurement of long-range heteronuclear coupling constants using the peak
intensity in classical 1D HMBC spectra.
AB - In this contribution, we show that the magnitude of heteronuclear long-range
coupling constants can be directly extracted from the classical 1D HMBC spectra,
as all multiplet lines of a cross-peak always and exclusively vanish for the
condition Delta = k/n JCH . To the best of our knowledge, this feature of the
classical HMBC has not yet been noticed and exploited. This condition holds true,
irrespective of the magnitude and numbers of additional active and passive
homonuclear n JHH' couplings. Alternatively, the n JCH value may also be
evaluated by fitting the peak's intensity in the individual spectra to its simple
sin(pin JCH Delta)exp(-Delta/T2eff ) dependence. Compared to the previously
proposed J-HMBC sequences that also use the variation of the cross-peak's
intensity for extracting the coupling constants, the classical HMBC pulse
sequence is significantly more sensitive.
PMID- 29336082
TI - Metabolomics Study of Cultivated Bulbus Fritillariae Cirrhosae at Different
Growth Stages using UHPLC-QTOF-MS Coupled with Multivariate Data Analysis.
AB - INTRODUCTION: Bulbus fritillariae cirrhosae (known as Chuan bei mu in China, BFC)
contain fritillaria steroidal alkaloids as the bioactive ingredients and are
widely used as traditional Chinese medicine for the treatment of cough and
phlegm. Due to limited wild resources, the cultivated species are becoming
predominantly used in Chinese traditional medicine markets. OBJECTIVE: To assess
the impact of different growth stages on the alkaloids of cultivated BFC and
establish a reference for quality control and guidance for appropriate harvesting
practices. METHODS: The ultra-high performance liquid chromatography quadrupole
time-of-flight mass spectrometry (UHPLC-QTOF-MS) metabolomic strategy was applied
to determine potential chemical markers for the discrimination and quality
control of cultivated BFC in different growth stages. The molecular feature
extraction and multivariate statistical analysis were applied to alkaloid
extraction and full metabolomic profiling of cultivated BFC for classification
and marker compound characterisation. RESULT: This approach allowed the
establishment of a fast and efficient comparative multivariate analysis of the
metabolite composition of 42 samples covering growth of cultivated BFC ranging in
age from one to seven years old. Four alkaloid compounds were identified in
cultivated BFC based on accurate mass, retention time, and MS/MS fragments. These
compounds may be used as potential chemical markers for the classification and
discrimination of cultivated BFC samples indifferent growth stages. CONCLUSIONS:
The proposed analytical method in combination with multivariate statistical
analysis comprised a useful and powerful strategy to explore the chemical
ingredients and transforming mechanisms of cultivated BFC and for quality
evaluation and control. Copyright (c) 2018 John Wiley & Sons, Ltd.
PMID- 29336083
TI - How sea level change mediates genetic divergence in coastal species across
regions with varying tectonic and sediment processes.
AB - Plate tectonics and sediment processes control regional continental shelf
topography. We examine the genetic consequences of how glacial-associated sea
level change interacted with variable nearshore topography since the last
glaciation. We reconstructed the size and distribution of areas suitable for
tidal estuary formation from the last glacial maximum, ~20 thousand years ago, to
present from San Francisco, California, USA (~38 degrees N) to Reforma, Sinaloa,
Mexico (~25 degrees N). We assessed range-wide genetic structure and diversity of
three codistributed tidal estuarine fishes (California Killifish, Shadow Goby,
Longjaw Mudsucker) along ~4,600 km using mitochondrial control region and cytB
sequence, and 16-20 microsatellite loci from a total of 524 individuals. Results
show that glacial-associated sea level change limited estuarine habitat to few,
widely separated refugia at glacial lowstand, and present-day genetic clades were
sourced from specific refugia. Habitat increased during postglacial sea level
rise and refugial populations admixed in newly formed habitats. Continental
shelves with active tectonics and/or low sediment supply were steep and hosted
fewer, smaller refugia with more genetically differentiated populations than on
broader shelves. Approximate Bayesian computation favoured the refuge
recolonization scenarios from habitat models over isolation by distance and
seaway alternatives, indicating isolation at lowstand is a major diversification
mechanism among these estuarine (and perhaps other) coastal species. Because sea
level change is a global phenomenon, we suggest this top-down physical control of
extirpation-isolation-recolonization may be an important driver of genetic
diversification in coastal taxa inhabiting other topographically complex coasts
globally during the Mid- to Late Pleistocene and deeper timescales.
PMID- 29336084
TI - Age onset of offending and serious mental illness among forensic psychiatric
patients: A latent profile analysis.
AB - BACKGROUND: Developmental typologies regarding age of onset of violence and
offending have not routinely taken account of the role of serious mental illness
(SMI), and whether age of onset of offending in relation to onset of illness
impacts on the manifestation of offending over the life course. AIMS: To test
whether forensic psychiatric patients can be classified according to age of onset
of SMI and offending, and, if so, whether subtypes differ by sex. METHODS:
Details of all 511 patients enrolled into a large forensic mental health service
in Ontario, Canada, in 2011 or 2012 were collected from records. RESULTS: A
latent profile analysis supported a 2-class solution in both men and women.
External validation of the classes demonstrated that those with a younger age
onset of serious mental illness and offending were characterised by higher levels
of static risk factors and criminogenic need than those whose involvement in both
mental health and criminal justice systems was delayed to later life.
CONCLUSIONS: Our findings present a new perspective on life course trajectories
of offenders with SMI. While analyses identified just two distinct age-of-onset
groups, in both the illness preceded the offending. The fact that our sample was
entirely drawn from those hospitalised may have introduced a selection bias for
those whose illness precedes offending, but findings underscore the complexity
and level of need among those with a younger age of onset. Copyright (c) 2018
John Wiley & Sons, Ltd.
PMID- 29336085
TI - Endotracheal tube placement during computed tomography of brachycephalic dogs
alters upper airway dimensional measurements.
AB - Computed tomography (CT) is used to document upper airway lesions in dogs with
brachycephalic obstructive airway syndrome. The presence of an endotracheal tube
during CT scanning is often required for general anesthesia. We hypothesized that
the endotracheal tube placement would change the soft tissue dimensions of the
upper airway. The aims of this prospective, method comparison study were to
evaluate the reliability of the previously reported upper airway CT measurements
with endotracheal tube placement, and to propose measurements that are minimally
affected by the endotracheal tube. Twenty brachycephalic dogs were included in
this study. Each dog underwent head/neck CT with an endotracheal tube, followed
by a second scan without the endotracheal tube. Ten measurements of the soft
palate, nasopharynx, and trachea were performed. Tracheal dimension was
significantly larger with the endotracheal tube compared to without, whereas the
soft palate cross-sectional area was significantly smaller with the endotracheal
tube than without the endotracheal tube. The influence of the endotracheal tube
on the caudal nasopharynx cross-sectional (transverse-sectional) area varied with
a mean proportional absolute difference of 35%. Rostral soft palate thickness,
tracheal perimeter, and cross-sectional area of the rostral nasopharynx were the
measurements least affected by the endotracheal tube (intraclass correlation
coefficient = 0.964, 0.967, and 0.951, respectively). Therefore, we proposed that
these three measurements may be most useful for future brachycephalic obstructive
airway syndrome studies that require CT scanning of intubated animals. However,
with endotracheal tube placement, measurements of soft palate length, caudal
nasopharyngeal cross-sectional area, and trachea height and width may not be
reliable.
PMID- 29336086
TI - Learning to blast a way into crime, or just good clean fun? Examining aggressive
play with toy weapons and its relation with crime.
AB - BACKGROUND: Researchers, such as Bandura, have proposed that children's mere
exposure to the use of play weapons encourages deviant displays of aggression,
but there is very little research to support this hypothesis of 20 years. AIM: To
examine the relationship between amount of weapon play and concurrent aggression
as well as later violent juvenile crime, while controlling for other variables
possibly influencing criminal pathways. METHOD: Using longitudinal survey data
collected from mothers and children (n = 2019) from age 5, with follow-up at age
15, correlations between children's play with toy weapons and juvenile
criminality were examined. Multivariate regression analyses were employed to
determine to what extent early childhood aggression, symptoms of attention
deficit hyperactivity disorder, and symptoms of depression were antecedents of
juvenile crime. RESULTS: For bivariate analysis between toy weapon play and
juvenile criminality, the effect size was small and not significant. The
relationship remained not significant once control variables were introduced into
the model. CONCLUSIONS AND IMPLICATIONS: The act of pretending to be aggressive
in childhood thus plays little role in predicting later criminality after other
factors, such as gender, attention deficit hyperactivity disorder or depression,
have been taken into account. Involvement in imaginative play with toy gun use in
early childhood is unlikely to be useful as a risk marker for later criminal
behaviour. Play fighting and war toy games may even be considered necessary
components within the frame of normal development. Copyright (c) 2018 John Wiley
& Sons, Ltd.
PMID- 29336087
TI - New Stretching Method for Aligning Gels: Its Application to the Measurement
Residual Chemical Shift Anisotropies (RCSAs) without the Need for Isotropic Shift
Correction.
AB - An existing gel stretching device is modified, permitting the use of organic
solvents for the study of small molecules. Different from the original device,
gels are stretched into 4 mm open-ended NMR tubes and then inserted into regular
5 mm NMR tubes. No open-ended tubes are inserted in the NMR probe avoiding the
risk of sample leaking. It is also shown that residual chemical shift
anisotropies (RCSAs) measured with the device are free of isotropic shift
interferences and corrections for them are not needed during the post-acquisition
data analysis. Three internal references for chemical shift were evaluated (CCl4
, CBr4 and TMS), being CCl4 the most convenient one to measure RCSAs in CDCl3 .
RCSAs measured with the modified stretching device using CCl4 as the internal
chemical shift reference were enough to determine the relative configuration of
three small molecules with an excellent degree of configuration discrimination.
PMID- 29336088
TI - Casual movement speed but not maximal locomotor capacity predicts mate searching
success.
AB - Maximal locomotor performance is often used as a proxy for fitness. Maximal speed
may be important under high-threat conditions, such as during predator escape.
However, animals do not always move at a speed that reflects their maximal
physiological capacities when undisturbed. The physiological factors that
determine the movement speed chosen by animals, such as minimization of energy
use, may be independent from maximal performance. As a result, the casual speed
at which individuals move when undisturbed in a given context may better
represent an individual's motivation to move. The casual speed may therefore be a
better predictor of fitness in natural contexts than maximal performance
capacity. We tested the hypothesis that casual movement speed rather than maximal
speed predicts fitness in the golden orb-web spider, Nephila plumipes. We
measured fitness in two separate contexts, mate-searching success and the
positional rank near a female. We show that casual but not maximal locomotor
speed predicted both aspects of fitness. Casual speed was linearly related to
maximal speed, indicating that casual speed is determined by physiological
optimization. Size and metabolic scope were not related to either maximal or
chosen speeds, indicating that the supply of ATP does not limit locomotor
performance in this species. Overall, our results demonstrate that locomotor
performance is related to fitness, but suggest that different types of
performance and not necessarily maximal physiological capacities are most
relevant for particular ecologically relevant tasks.
PMID- 29336089
TI - Corrigendum.
PMID- 29336090
TI - Microsphere Assemblies via Phosphonate Monoester Coordination Chemistry.
AB - By complexing a bent phosphonate monoester ligand with cobalt(II), coupled with
in situ ester hydrolysis, coordination microspheres (CALS=CALgary Sphere) are
formed whereas the use of the phosphonic acid directly resulted in a sheet-like
structure. Manipulation of the synthetic conditions gave spheres with different
sizes, mechanical stabilities, and porosities. Time-dependent studies determined
that the sphere formation likely occurred through the formation of a Co2+ and
ligand chain that propagates in three dimensions through different sets of
interactions. The relative rates of these assembly processes versus annealing by
ester hydrolysis and metal dehydration determine the growth of the microspheres.
Hardness testing by nanoindentation is carried out on the spheres and sheets.
Notably, no templates or capping agents are employed, the growth of the spheres
is intrinsic to the ligand geometry and the coordination chemistry of cobalt(II)
and the phosphonate monoester.
PMID- 29336092
TI - Development and validation of a scoring system to predict progression to acute-on
chronic liver failure in patients with acute exacerbation of chronic hepatitis B.
AB - AIM: The aim of this study was to develop and validate a scoring system to
predict the progression to acute-on-chronic liver failure (ACLF) in patients with
acute exacerbation (AE) of chronic hepatitis B (CHB). METHODS: The baseline
characteristics of 474 patients with AE of CHB were retrospectively reviewed; 280
and 194 patients were randomly assigned to the derivation and validation cohorts,
respectively. Univariate risk factors associated with ACLF development were
entered into a multivariate logistic regression. The score model was established,
and its predictive value was evaluated by the receiver operating characteristic
(ROC) curve and the area under the ROC curve (AUROC). RESULTS: Hepatitis B virus
(HBV) DNA, international normalized ratio (INR) of prothrombin time, and patient
age were identified as independent risk factors associated with progressing to
ACLF. The prediction model was established as R = -13.323 + 0.553 * log HBV-DNA
(copies/mL) + 3.631* INR + 0.053 * age. The AUROCs of our prediction model were
higher than those of the Model for End-stage Liver Disease (MELD) and MELD-sodium
(Na) for both cohorts. At the cut-off value of -2.43, our prediction model had
higher sensitivity (87.5%), specificity (73.6%), positive predictive value
(23.0%), positive likelihood ratio (3.30), and lower negative likelihood ratio
(0.17) in the validation cohort than those of MELD and MELD-Na. CONCLUSION: The
independent risk factors associated with progressing to ACLF in patients with AE
of CHB are HBV-DNA, INR, and age. Our risk prediction model is useful for
predicting the development of ACLF.
PMID- 29336093
TI - Heart failure with mid-range ejection fraction: causes and consequences.
PMID- 29336091
TI - Drug resistance in anaplastic lymphoma kinase-rearranged lung cancer.
AB - The anaplastic lymphoma kinase (ALK) gene encodes a receptor tyrosine kinase, and
many kinds of ALK fusion genes have been found in a variety of carcinomas. There
is almost no detectable expression of ALK in adults. However, through ALK gene
rearrangement, the resultant ALK fusion protein is aberrantly overexpressed and
dimerized through the oligomerization domains, such as the coiled-coil domain, in
the fusion partner that induces abnormal constitutive activation of ALK tyrosine
kinase. This results in dysregulated cell proliferation. ALK gene rearrangement
has been observed in 3%-5% of non-small-cell lung cancers, and multiple ALK
inhibitors have been developed for the treatment of ALK-positive lung cancer.
Among those inhibitors, in Japan, 3 (4 in the USA) ALK tyrosine kinase inhibitors
(TKIs) have been approved and are currently used in clinics. All of the currently
approved ALK-TKIs have been shown to induce marked tumor regression in ALK
rearranged non-small-cell lung cancer; however, tumors inevitably relapse because
of acquired resistance within a few years. This review focuses on ALK-TKIs, their
resistance mechanisms, and the potential therapeutic strategies to overcome
resistance.
PMID- 29336095
TI - Sleep hygiene, insomnia and mental health.
PMID- 29336094
TI - Sympathetic neurovascular regulation during pregnancy: A longitudinal case series
study.
AB - NEW FINDINGS: What is the main observation in this case? The main observation of
this case report is that during pregnancy there is a progressive sympatho
excitation in basal conditions and under stress, which is offset by a concurrent
reduction in neurovascular transduction. Strong correlations between autonomic
nervous system activity and sex hormones (oestrogen and progesterone),
vasopressin and aldosterone were found. What insights does it reveal? Our
findings suggest that hormonal surges might be associated with central
sympathetic activation. ABSTRACT: The adaptations of sympathetic nerve activity
(SNA) during pregnancy remain poorly understood. An increase in blood volume,
cardiac output and SNA, with a concomitant drop in total peripheral resistance
(TPR), suggest that during pregnancy there is a reduced transduction of SNA into
TPR. Most of these findings have originated from cross-sectional studies; thus,
we conducted a longitudinal assessment of SNA and TPR in two participants.
Measurements were made before pregnancy (early follicular phase), on four
occasions during pregnancy and at 2 months postpartum. Mean arterial pressure and
cardiac output were used to calculate TPR. The SNA was measured using
microneurography (peroneal nerve). There was a gestation-dependent increase in
SNA burst frequency (r2 = 0.96, P = 0.009). Neurovascular transduction, however,
decreased by 53% in both women. Sympathetic hyperactivity was reversed
postpartum, whereas neurovascular transduction remained lower. These longitudinal
data highlight the progressive sympatho-excitation of pregnancy, which is offset
by a concurrent reduction in neurovascular transduction.
PMID- 29336096
TI - Fe2 Si5 N8 : Access to Open-Shell Transition-Metal Nitridosilicates.
AB - Highly condensed nitridosilicates doped with Eu2+ or Ce3+ play an important role
in saving energy by converting the blue light of (In,Ga)N-LEDs. Although
nitridosilicates are known for great structural variety based on covalent anionic
Si-N networks, elemental variety is restricted. Presenting a significant
extension of the latter, this work describes a general access to open-shell
transition-metal nitridosilicates. As a proof-of-principle, the first iron
nitridosilicate, namely Fe2 Si5 N8 , was prepared by exchanging Ca2+ in alpha-Ca2
Si5 N8 applying a FeCl2 melt (salt metathesis). The title compound was analyzed
by powder X-ray diffraction, EDX, ICP-OES, combustion analysis, TG/DSC, Mossbauer
spectroscopy and magnetic susceptibility measurements. Furthermore, the structure
of alpha-Ca2 Si5 N8 was determined at 1073 and 1173 K confirming the anionic
network of alpha-Ca2 Si5 N8 providing possible migration pathways for the ion
exchange reaction.
PMID- 29336097
TI - Identification of dementia using standard clinical assessments by primary care
physicians in Japan.
AB - AIM: The aim of the present study was to develop a way of identifying dementia
using clinical assessments made by primary care physicians under the existing
medical care system in Japan. METHODS: A total of 623 people aged >=65 years
underwent standard clinical assessments by primary care physicians under the long
term-care insurance program to determine their grade of activities of daily
living related to dementia. To examine the validity of the diagnosis,
neuropsychiatrists carried out further diagnosis of dementia for all the
participants. We regarded the dementia patients who received care for disability
under the long-term care insurance program as having disabling dementia. RESULTS:
Multivariable odds ratio (95% confidence interval) in single-grade increments of
the activity was 2.1 (1.7-2.5) for dementia and 2.8 (2.2-3.4) for disabling
dementia. The grades >=I and >=IIa were near the upper-left corner in the
receiver operating characteristic curves. Setting the cut-off point at grades >=I
or >=IIa yielded a higher integrated discrimination improvement, suggesting a
major improvement in reducing misclassification by using these cut-off points.
When we used grades >=I as the cut-off point, the sensitivity (95% confidence
limits) was 65% (58-72%) and the specificity was 93% (91-96%) for dementia, and
the corresponding values in grades >=IIa were 54% (47-62%) and 96% (94-97%). The
corresponding values for disabling dementia were 83% (76-90%), 92% (90-95%), 73%
(65-80%) and 96% (94-97%). CONCLUSIONS: Our findings suggest that selection of
grades >=I or >=IIa as the cut-off point would reduce instances of
misclassification in the identification of dementia and disabling dementia.
Geriatr Gerontol Int 2018; 18: 738-744.
PMID- 29336098
TI - Increasing the knowledge, identification and treatment of osteoporosis through
education and shared decision-making with residents living in a retirement
village community.
AB - OBJECTIVE: This pilot study explored whether individual goal setting in a
retirement village setting could improve strategies to strengthen bones in an
ageing population and help prevent osteoporosis. METHODS: A two-phased
osteoporosis prevention program was developed, piloted and evaluated involving a
group education session followed by the development of individualised Bone Plans
based upon personal understanding of individual fracture risk and lifestyle
factors. RESULTS: A significant improvement in knowledge and understanding of
factors to prevent and manage osteoporosis was achieved, and changes in lifestyle
behaviours were sustained at six months. CONCLUSION: Success was due to education
by specialist medical and health personnel, flexibility of goal setting, use of
group sessions and location of the program within the retirement community
setting. The 'Mind Your Bones' program is a feasible and acceptable way to
translate preventative bone health messages to a large number of people via the
retirement village network.
PMID- 29336099
TI - Evolving rationale for post-mastectomy radiation.
PMID- 29336100
TI - Silver(I)-Catalyzed Widely Applicable Aerobic 1,2-Diol Oxidative Cleavage.
AB - The oxidative cleavage of 1,2-diols is a fundamental organic transformation. The
stoichiometric oxidants that are still predominantly used for such oxidative
cleavage, such as H5 IO6 , Pb(OAc)4 , and KMnO4 , generate stoichiometric
hazardous waste. Herein, we describe a widely applicable and highly selective
silver(I)-catalyzed oxidative cleavage of 1,2-diols that consumes atmospheric
oxygen as the sole oxidant, thus serving as a potentially greener alternative to
the classical transformations.
PMID- 29336101
TI - Recurrence of vulval intraepithelial neoplasia following treatment with cidofovir
or imiquimod: results from a multicentre, randomised, phase II trial (RT3VIN).
AB - OBJECTIVE: To compare the recurrence rates after complete response to topical
treatment with either cidofovir or imiquimod for vulval intraepithelial neoplasia
(VIN) 3. DESIGN: A prospective, open, randomised multicentre trial. SETTING: 32
general hospitals located in Wales and England. POPULATION OR SAMPLE: 180
patients were randomised consecutively between 21 October 2009 and 11 January
2013, 89 to cidofoovir (of whom 41 completely responded to treatment) and 91 to
imiquimod (of whom 42 completely responded to treatment). METHODS: After 24 weeks
of treatment, complete responders were followed up at 6-monthly intervals for 24
months. At each visit, the Common Terminology Criteria for Adverse Events (CTCAE)
v3.0 was assessed and any new lesions were biopsied for histology. MAIN OUTCOME
MEASURES: Time to histologically confirmed disease recurrence (any grade of VIN).
RESULTS: The median length of follow up was 18.4 months. At 18 months, more
participants were VIN-free in the cidofovir arm: 94% (95% CI 78.2-98.5) versus
71.6% (95% CI 52.0-84.3) [univariable hazard ratio (HR) 3.46, 95% CI 0.95-12.60,
P = 0.059; multivariable HR 3.53, 95% CI 0.96-12.98, P = 0.057). The number of
grade 2+ events was similar between treatment arms (imiquimod: 24/42 (57%) versus
cidofovir: 27/41 (66%), chi2 = 0.665, P = 0.415), with no grade 4+. CONCLUSIONS:
Long-term data indicates a trend towards response being maintained for longer
following treatment with cidofovir than with imiquimod, with similar low rates of
adverse events for each drug. Adverse event rates indicated acceptable safety of
both drugs TWEETABLE ABSTRACT: Long-term follow up in the RT3VIN trial suggests
cidofovir may maintain response for longer than imiquimod.
PMID- 29336102
TI - Behavioural responses of the yellow emitting annelid Tomopteris helgolandica to
photic stimuli.
AB - In contrast to most mesopelagic bioluminescent organisms specialised in the
emission and reception of blue light, the planktonic annelid Tomopteris
helgolandica produces yellow light. This unusual feature has long been suggested
to serve for intraspecific communication. Yet, this virtually admitted hypothesis
has never been tested. In this behavioural study of spectral colour sensitivity,
we first present an illustrated repertoire of the postures and action patterns
described by captive specimens. Then video tracking and motion analysis are used
to quantify the behavioural responses of singled out worms to photic stimuli
imitating intraspecific (yellow) or interspecific (blue) bioluminescent signals.
We show the ability of T. helgolandica to react and to contrast its responses to
bioluminescent-like blue and yellow light signals. In particular, the attractive
effect of yellow light and the variation of angular velocity observed according
to the pattern of yellow stimuli (flashes versus glows) support the intraspecific
communication hypothesis. However, given the behavioural patterns of T.
helgolandica, including mechanically induced light emission, the possibility that
bioluminescence may be part of escape/defence responses to predation, should
remain an open question.
PMID- 29336103
TI - Staff preparedness for providing palliative and end-of-life care in long-term
care homes: Instrument development and validation.
AB - AIM: Although much attention has been on integrating the palliative care approach
into services of long-term care homes for older people living with frailty and
progressive diseases, little is known about the staff preparedness for these new
initiatives. The present study aimed to develop and test the psychometric
properties of an instrument for measuring care home staff preparedness in
providing palliative and end-of-life care. METHODS: A 16-item instrument,
covering perceived knowledge, skill and psychological readiness, was developed. A
total of 247 staff members of different ranks from four care homes participated
in the study. Exploratory factor analysis using the principal component analysis
extraction method with varimax rotation was carried out for initial validation.
Known group comparison was carried out to examine its discriminant validity.
Reliability of the instrument was assessed based on test-retest reliability of a
subsample of 20 participants and the Cronbach's alpha of the items. RESULTS:
Exploratory factor analysis showed that the instrument yielded a three-factor
solution, which cumulatively accounted for 68.5% of the total variance. Three
subscales, namely, willingness, capability and resilience, showed high internal
consistency and test-retest reliability. It also showed good discriminant
validity between staff members of professional and non-professional groups.
CONCLUSIONS: This is a brief, valid and reliable scale for measuring care home
staff preparedness for providing palliative and end-of-life care. It can be used
to identify their concerns and training needs in providing palliative and end-of
life care, and as an outcome measure to evaluate the effects of interventional
studies for capacity building in this regard. Geriatr Gerontol Int 2018; 18: 745
749.
PMID- 29336104
TI - Early intervention in bipolar disorders: Where we are now and need to go next.
PMID- 29336105
TI - Senescence chips for ultrahigh-throughput isolation and removal of senescent
cells.
AB - Cellular senescence plays an important role in organismal aging and age-related
diseases. However, it is challenging to isolate low numbers of senescent cells
from small volumes of biofluids for downstream analysis. Furthermore, there is no
technology that could selectively remove senescent cells in a high-throughput
manner. In this work, we developed a novel microfluidic chip platform, termed
senescence chip, for ultrahigh-throughput isolation and removal of senescent
cells. The core component of our senescence chip is a slanted and tunable 3D
micropillar array with a variety of shutters in the vertical direction for rapid
cell sieving, taking advantage of the characteristic cell size increase during
cellular senescence. The 3D configuration achieves high throughput, high recovery
rate, and device robustness with minimum clogging. We demonstrated proof-of
principle applications in isolation and enumeration of senescent mesenchymal stem
cells (MSCs) from undiluted human whole blood, and senescent cells from mouse
bone marrow after total body irradiation, with the single-cell resolution. After
scale-up to a multilayer and multichannel structure, our senescence chip achieved
ultrahigh-throughput removal of senescent cells from human whole blood with an
efficiency of over 70% at a flow rate of 300 ml/hr. Sensitivity and specificity
of our senescence chips could be augmented with implementation of multiscale size
separation, and identification of background white blood cells using their cell
surface markers such as CD45. With the advantages of high throughput, robustness,
and simplicity, our senescence chips may find wide applications and contribute to
diagnosis and therapeutic targeting of cellular senescence.
PMID- 29336106
TI - Best practice perioperative strategies and surgical techniques for preventing
caesarean section surgical site infections: a systematic review of reviews and
meta-analyses.
AB - BACKGROUND: Surgical site infection (SSI) following caesarean section is a
problem for women and health services. Caesarean section is a high volume
procedure and the estimated incidence of SSI may be as high as 9%. OBJECTIVES:
The objective of this study was to identify a suite of perioperative strategies
and surgical techniques that reduce the risk of SSI following caesarean section.
SEARCH STRATEGY: Six electronic databases were searched to systematically review
literature reviews, systematic reviews and meta-analyses published from 2006 to
2016. Search terms included: endometritis, SSI, caesarean section, meta-analysis,
review, systematic. SELECTION CRITERIA: Studies were sought in which competing
perioperative strategies and surgical techniques relevant for caesarean section
were identified and quantifiable infection outcomes were reported. General
infection control strategies were excluded. DATA COLLECTION AND ANALYSIS: Data on
study characteristics and clinical effectiveness were extracted. Quality,
including bias within individual studies, was examined using a modified A
Measurement Tool to Assess Systematic Reviews (AMSTAR) checklist. Recommendations
for SSI risk-reducing strategies were developed using the Grading of
Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN
RESULTS: Of 466 records retrieved, 44 studies were selected for the evidence
synthesis. Recommended strategies were: administer pre-incision antibiotic
prophylaxis, prepare the vagina with iodine-povidone solution and spontaneous
placenta removal. CONCLUSIONS: We recommend clinicians implement pre-incision
antibiotic prophylaxis, vaginal preparation and spontaneous placenta removal as
an infection control bundle for caesarean section. FUNDING: Queensland University
of Technology. TWEETABLE ABSTRACT: Infection control for caesarean: pre-incision
AB prophylaxis, vaginal prep, spontaneous placenta removal.
PMID- 29336107
TI - Centrality of spirituality/religion in the culture of palliative care service in
Indonesia: An ethnographic study.
AB - Experiencing life-threatening illness could impact on an individual's
spirituality or religious beliefs. In this paper, we report on a study which
explored cultural elements that influence the provision of palliative care for
people with cancer. A contemporary ethnographic approach was adopted.
Observations and interviews were undertaken over 3 months with 48 participants,
including palliative care staff, patients, and their families. An ethnographic
data analysis framework was adopted to assist in the analysis of data at item,
pattern, and structural levels. Religion was identified as central to everyday
life, with all participants reporting being affiliated to particular religions
and performing their religious practices in their daily lives. Patients'
relatives acknowledged and addressed patients' needs for these practices. Staff
provided spiritual care for the patients and their relatives in the form of
religious discussion and conducting prayers together. An understanding that
religious and spiritual practices are integral cultural elements and of
fundamental importance to the holistic health of their patients is necessary if
health-care professionals are to support patients and their families in end-of
life care.
PMID- 29336108
TI - Reversible CO2 Addition to a Si=O Bond and Synthesis of a Persistent SiO2 -CO2
Cycloadduct Stabilized by a Lewis Donor-Acceptor Ligand.
AB - The donor-stabilized sila-beta-lactone 1 reacts with CO2 via a remarkable
reversible [2+2]-cycloaddition reaction to form the spiro-cyclic silicon
carbonate derivative 2. Furthermore, photolysis of 2 under pressure of CO2
affords the first persistent SiO2 -CO2 cycloadduct 3, presenting a Si2 O4 -like
structure, which is stabilized by a Lewis donor-acceptor type ligand. As
predicted by theoretical calculations, in marked contrast to the
thermodynamically stable SiO2 dimer, the SiO2 -CO2 mixed cycloadduct 3 is labile
and readily releases CO2 .
PMID- 29336109
TI - Moderate hypofractionation for prostate cancer: A user's guide.
AB - Three large randomised controlled trials have been published in the last year
demonstrating the non-inferiority of moderate hypofractionation compared to
conventional fractionation for localised prostate cancer with respect to both
disease control and late toxicity at 5 years. Furthermore, no clinically
significant differences in patient-reported outcomes have emerged. More mature
follow-up data are now also available from phase 2 studies confirming that
moderate hypofractionation is associated with low rates of significant toxicity
at 10 years. Moving forward it is likely that appropriate patient selection,
integration of androgen deprivation and attention to optimising technique will
play a more important role than modest differences in dose-fractionation
schedules. Here we briefly review the evidence, discuss issues of patient
selection and provide an approach to implementing moderately hypofractionated
radiation therapy for prostate cancer in clinical practice.
PMID- 29336110
TI - Stabilization of the Pentazolate Anion in a Zeolitic Architecture with Na20 N60
and Na24 N60 Nanocages.
AB - The experimental detection and synthesis of pentazole (HN5 ) and its anion (cyclo
N5- ) have been actively pursued for the past hundred years. The synthesis of an
aesthetic three-dimensional metal-pentazolate framework (denoted as MPF-1) is
presented. It consists of sodium ions and cyclo-N5- anions in which the isolated
cyclo-N5- anions are preternaturally stabilized in this inorganic open framework
featuring two types of nanocages (Na20 N60 and Na24 N60 ) through strong metal
coordination bonds. The compound MPF-1 is indefinitely stable at room temperature
and exhibits high thermal stability relative to the reported cyclo-N5- salts.
This finding offers a new approach to create metal-pentazolate frameworks (MPFs)
and enables the future exploration of interesting pentazole chemistry and also
related functional materials.
PMID- 29336111
TI - Beyond mere pill taking: SMS reminders for HIV treatment adherence delivered to
mobile phones of clients in a community support network in Australia.
AB - SMS reminders sent to personal mobiles are increasingly used by clinical services
to promote patient engagement, including adherence to antiretroviral treatment
(ART) for HIV. From August to September 2015, a 6-week, randomised SMS reminder
for ART adherence intervention was implemented among 98 HIV-positive clients of
Australian's largest HIV charitable organisation located in Sydney. This was
followed by a mixed-method evaluation, comprising a self-completed online survey
and a one-to-one interview. Of the 62 survey participants, all being men, the
majority were gay (85.5%) and living long-term with HIV (median year of HIV
diagnosis = 1998). While everyone was on ART, a substantial proportion (n = 27,
43.5%) had interrupted treatment in the past. At the end of the intervention,
based on the standard SMAQ measure, 82% had consistently adhered to ART in the
previous week. While there was no statistically significant intervention effect,
perceiving less stigma were independently associated with better ART adherence
(adjusted odds ratio = 0.37; 95% CI 0.16-0.89; P = .026). Of the 11 interviewees,
despite limited add-on effects on individual ART adherence, the campaign was well
received as a unique community support service. This study underscores the
essential role of empowerment through enhancing disease self-management,
increasing social support and reducing stigma, particularly for long-term HIV
survivors. SMS messaging, part of mHealth, delivered by community services could
have broader impacts on reducing health and social inequity.
PMID- 29336112
TI - Is there an association of ABO blood groups and Rhesus factor with alopecia
areata?
AB - BACKGROUND/OBJECTIVES: Alopecia areata (AA) is an autoimmune disease
characterized by noncicatricial hair loss localized on hair, beard, mustache,
eyebrow, eyelash, and sometimes on the body. Although etiopathogenesis is not
fully understood, many studies show remarkable associations between various
diseases and ABO blood groups. However, there is no study with AA and blood
groups. METHODS: Healthy people and patients with AA were included in this study.
A total of 155 patients with AA and 299 healthy controls were included in the
study. RESULTS: ABO blood group distribution in patients with AA and distribution
of healthy donors were similar. However, Rhesus factor positivity in the AA group
was significantly higher than in healthy donors. The relationship between stress
and AA was high as known. But, ABO blood group and Rhesus factor were not in a
significant connection with stress. CONCLUSION: We conclude that there was no
association between ABO blood group and AA, but the observed distribution of
Rhesus blood group differed slightly but significantly from that of the healthy
population. The result of the study shows a small but statistically significant
difference in the Rh blood group between patients with AA and the healthy
population blood groups. This result is important because it suggests that
genetic factors may influence the development of AA. The role of blood groups in
the development of AA remains to be determined. We believe that the studies which
will be carried out in other centers with wider series will be more valuable to
support this hypothesis.
PMID- 29336113
TI - Comments on Famulski and Halloran AJT i-IFTA letter.
PMID- 29336114
TI - Nucleolar and spindle-associated protein 1 is a tumor grade correlated prognosis
marker for glioma patients.
AB - AIMS: Despite therapeutic advances in glioma management including surgery,
radiation, and chemotherapy, the improvement of patient outcome is far from
satisfactory. Nucleolar and spindle-associated protein 1 (NUSAP1) is an important
functional protein during mitosis, and its abnormal expression is implicated in
progression of different types of tumors. However, the role of NUSAP1 in gliomas
remains unclear. METHODS: NUSAP1 expression in gliomas with different grades was
investigated based on GEO glioma datasets. Kaplan-Meier survival analysis was
used to evaluate its prognostic significance. In vitro assays were also performed
to evaluate effects of NUSAP1 on malignant phenotypes of glioma cells by
silencing NUSAP1. RESULTS: NUSAP1 expression was correlated not only with glioma
grade but also with prognosis of glioma patients. NUSAP1 depletion suppressed
proliferation of U251 cells by inducing cell cycle arrest at G2/M phase and
apoptosis. NUSAP1 depletion rendered U251 cells impaired migratory ability as
well. CONCLUSION: NUSAP1 is a potential prognosis marker for glioma patients and
therapeutic strategies targeting NUSAP1 might hold promise in improving glioma
treatment.
PMID- 29336115
TI - Insight into the inhibitor discrimination by FLT3 F691L.
AB - Fms-like tyrosine kinase 3 (FLT3) belongs to the receptor tyrosine kinase family
and expressed in hematopoietic progenitor cells. FLT3 gene mutations are reported
in ~30% of acute myeloid leukemia cases. FLT3 kinase domain mutation F691L is one
of the common causes of acquired resistance to the FLT3 inhibitors including
quizartinib. MZH29 and crenolanib were previously reported to inhibit FLT3 F691L.
However, crenolanib was reported for the moderate inhibition. We found that
Glu661and Asp829 were the most significant residues to target the FLT3 F691L
which contribute most significantly to the binding energy with MZH29 and
crenolanib. These interactions were found absent with quizartinib. Further free
energy landscape analysis revealed that FLT3 F691L bound to MZH29 and crenolanib
was more stable as compared to quizartinib.
PMID- 29336116
TI - The retina of the collared peccary (Pecari tajacu): structure and function.
AB - OBJECTIVE: To study retinal morphology and function in the collared peccary, an
ungulate species distantly related to the domestic pig. ANIMAL STUDIES: Twenty
captive peccaries anesthetized for routine health examinations. Procedures No
abnormalities were noted on a complete ophthalmic examination. Fundi were
examined ophthalmoscopically and photographed. The eyes of an individual that
died of unrelated, nonocular reasons were studied histologically and by
immunohistochemistry. Scotopic, mixed rod-cone, and photopic electroretinography
(ERG) responses were recorded using the 'QuickRetCheck' (n = 6) and 'Dog
diagnostic' (n = 5) protocols of the Handheld Multispecies ERG (HMsERG). RESULTS:
The fundus of the peccary is atapetal, with varying amounts of pigmentation seen
ophthalmoscopically, and histologically in the retinal pigment epithelium (RPE)
and choroid. The retina is holangiotic with dichotomously branching vessels.
These cross, and apparently loop on, the optic disk surface, but no venous circle
was seen. Immunohistochemistry suggests a high concentration of cone
photoreceptors with red/green cones being more abundant than blue cones. Rod ERG
responses were very low with no evident dark adaptation. Mixed rod-cone and cone
ERG response amplitudes were low compared to those of domestic pigs, but quite
similar to those of minipigs. CONCLUSIONS: To the best of our knowledge, this
study describes the collared peccary's retinal features for the first time. A
comparison of our findings with data from other ungulate species shows some
similarities between the peccary and pig retinas. Further studies are warranted
to determine whether the peccary can be used alongside the pig as an animal model
in retinal studies.
PMID- 29336117
TI - Prussian Blue-Derived Iron Phosphide Nanoparticles in a Porous Graphene Aerogel
as Efficient Electrocatalyst for Hydrogen Evolution Reaction.
AB - Tailoring of new hydrogen evolution reaction (HER) electrocatalyst with earth
abundant elements is important for large scale water splitting and hydrogen
production. In this work, we present a simple synthetic method for incorporating
iron phosphide (FeP) particles into three-dimensional (3D) porous graphene
aerogel (GA) structure. The FeP formed in porous 3D GA (FeP/GA) is derived from
electroactive Fe hexacyanoferrate (FeHCF). The advantage of incorporating FeP, in
the porous 3D graphene network enables high accessibility for HER. As synthesized
FeP/GA catalyst shows good electrocatalytic activity for HER in both acidic and
alkaline solutions. The developed method can be useful for synthesizing metal
hexacyanoferrate derived mono/bimetal phosphide catalyst in porous 3D graphene
aerogels.
PMID- 29336118
TI - Resveratrol Potently Counteracts Quercetin Starvation-Induced Autophagy and
Sensitizes HepG2 Cancer Cells to Apoptosis.
AB - SCOPE: Resveratrol (RSV) has been described as a potent antioxidant,
antisteatotic, and antitumor compound, and it has also been identified as a
potent autophagy inducer. On the other hand, quercetin (QCT) is a dietary
flavonoid with known antitumor, anti-inflammatory, and antidiabetic effects.
Additionally, QCT increases autophagy. To study the hypothetical synergistic
effect of both compounds, we test the combined effect of QCT and RSV on the
autophagy process in HepG2 cells. METHODS AND RESULTS: Autophagy is studied by
western blotting, real-time RT-PCR, and cellular staining. Our results clearly
indicate a bifunctional molecular effect of RSV. Both polyphenols are
individually able to promote autophagy. Strikingly, when RSV is combined with
QCT, it promotes a potent reduction of QCT-induced autophagy and influences
proapoptotic signaling. CONCLUSION: RSV acts differentially on the autophagic
process depending on the cellular energetic state. We further characterize the
molecular mechanisms related to this effect, and we observe that AMP-activated
protein kinase (AMPK) phosphorylation, heme oxygenase 1 (HO-1) downregulation,
lysosomal membrane permeabilization (LMP), and Zinc (Zn2+ ) dynamics could be
important modulators of such RSV-related effects and could globally represent a
promising strategy to sensitize cancer cells to QCT treatment.
PMID- 29336119
TI - Evaluations of UltraiQ software for objective ultrasound image quality assessment
using images from a commercial scanner.
AB - We evaluated a commercially available software package that uses B-mode images to
semi-automatically measure quantitative metrics of ultrasound image quality, such
as contrast response, depth of penetration (DOP), and spatial resolution
(lateral, axial, and elevational). Since measurement of elevational resolution is
not a part of the software package, we achieved it by acquiring phantom images
with transducers tilted at 45 degrees relative to the phantom. Each measurement
was assessed in terms of measurement stability, sensitivity, repeatability, and
semi-automated measurement success rate. All assessments were performed on a GE
Logiq E9 ultrasound system with linear (9L or 11L), curved (C1-5), and sector (S1
5) transducers, using a CIRS model 040GSE phantom. In stability tests, the
measurements of contrast, DOP, and spatial resolution remained within a +/-10%
variation threshold in 90%, 100%, and 69% of cases, respectively. In sensitivity
tests, contrast, DOP, and spatial resolution measurements followed the expected
behavior in 100%, 100%, and 72% of cases, respectively. In repeatability testing,
intra- and inter-individual coefficients of variations were equal to or less than
3.2%, 1.3%, and 4.4% for contrast, DOP, and spatial resolution (lateral and
axial), respectively. The coefficients of variation corresponding to the
elevational resolution test were all within 9.5%. Overall, in our assessment, the
evaluated package performed well for objective and quantitative assessment of the
above-mentioned image qualities under well-controlled acquisition conditions. We
are finding it to be useful for various clinical ultrasound applications
including performance comparison between scanners from different vendors.
PMID- 29336120
TI - The cognitive profile of Sotos syndrome.
AB - Sotos syndrome is a congenital overgrowth disorder, associated with intellectual
disability. Previous research suggests that Sotos syndrome may be associated with
relative strength in verbal ability and relative weakness in non-verbal reasoning
ability but this has not been explicitly assessed. To date, the cognitive profile
of Sotos syndrome is unknown. Cognitive abilities of a large and representative
sample of individuals with Sotos syndrome (N = 52) were assessed using the
British Ability Scales (BAS3). The majority of participants had intellectual
disability or borderline intellectual functioning. The cluster score profile
analysis revealed a consistent verbal ability > non-verbal reasoning ability
profile. Four specific criteria were proposed as the Sotos syndrome cognitive
profile (SSCP): verbal ability > non-verbal reasoning ability; quantitative
reasoning T-score or matrices T-score <20th percentile; quantitative reasoning T
score < mean T-score; recognition of designs T-score or recognition of pictures T
score > mean T-score. Of the 35 participants included in the profile analysis, 28
met all four SSCP criteria, yielding a sensitivity of 0.8. The sensitivity of
each of the SSCP criteria was >0.9. Individuals with Sotos syndrome display a
clear and consistent cognitive profile, characterized by relative strength in
verbal ability and visuospatial memory but relative weakness in non-verbal
reasoning ability and quantitative reasoning. This has important implications for
the education of individuals with Sotos syndrome.
PMID- 29336121
TI - Inter- and intra-operator reliability in patient-specific template positioning
for total hip arthroplasty. A cadaver study.
AB - BACKGROUND: The implantation of the acetabular cup essentially determines the
clinical outcome of total hip arthroplasty. To address this issue, the aim of
this study was to build patient-specific instruments (PSIs) with various
reference surfaces, followed by in vitro investigations to examine the inter- and
intra-operator reliability as well as the overall precision of these patient
specific templates. METHODS: Seven human hemi-pelvis specimens were used for this
study. After a CT scan, PSIs with different imprint heights were created. The
overall precision of the templates and the inter- and intra-operator
reliabilities were calculated. RESULTS: Strong differences in precision between
the PSI designs could be observed. The desired orientation of the acetabular cup
could be adjusted with a precision of up to 1.55 degrees . CONCLUSION: Based on
our results, we believe that the application of the PSI-based acetabular cup
positioning in total hip arthroplasty procedures can potentially increase the
precision of cup placement.
PMID- 29336122
TI - LETTER TO EDITOR.
PMID- 29336123
TI - Balance Assessment in Deaf Children and Teenagers Prior to and Post Capoeira
Practice through the Berg Balance Scale.
AB - INTRODUCTION: Hearing loss changes the functionality and body structure a
disability that limits activity and restricts the participation of the individual
in situations of daily life. It is believed that capoeira can help people with
visual disabilities to minimize these deficits. BSE is a low specificity scale
that evaluates objectively and functionally aspects of balance and risk of falls
in the elderly and children, including the effect of environment on balance
function. OBJECTIVE: The objective of the research is to analyze deaf children
and adolescents prior to and post-practice of capoeira using the Berg Balance
Scale (BBS). METHODS: Quantitative, clinical and observational studies. Twenty
five deaf children between 10 and 16 years old of both genders were assessed. BBS
was applied in two stages: before starting capoeira and after 6 months of
training. The one-hour classes were held once a week for quantitative evaluation
purposes. The subjects were divided and evaluated in two groups (10-13 years old
and 14-16 years old). RESULTS: There was a significant statistical difference in
BBS scores. The general group and the group of 10-13 years old (p = 0.0251)
showed an increase in scores after practicing capoeira (p = 0.0039). There were
no statistically significant differences in the group from 14 to 16 years of age
(p = 0.0504). CONCLUSION: Using the Berg Balance Scale, it was possible to
observe an improvement in the balance of the group of children and adolescents
who practiced capoeira, and consequently, a decrease in the risk of falling.
PMID- 29336124
TI - Masking Treatment and its Effect on Tinnitus Parameters.
AB - OBJECTIVE: Tinnitus is described as the perception of sound without any external
acoustic stimulation. Any pathology of auditory pathways or any system of the
human body may result with tinnitus. The pathophysiology of tinnitus accompanying
the disorders of auditory system is not fully understood and there is not any
particular effective treatment method has been specified. Tinnitus masking
therapy has been reported as an effective treatment modality in the treatment of
tinnitus. In this study, the results of tinnitus masking treatment on the
parameters were evaluated prospectively. PATIENTS AND METHODS: Patients with
normal physical examination was enrolled in the study. Blood tests (complete
blood count, biochemical analysis of lipid profile, and thyroid hormones), pure
tone audiometry, tympanometric measurement of the middle ear pressure and
stapedial reflexes were performed, Sixty six patients with normal results of
blood tests and normal hearing thresholds with type A tympanogram were included.
Tinnitus sufferers questionnaires (socio-demographics, clinical information,
Tinnitus Handicap Inventory (THI), Beck Depression Inventory (BDI) was filled,
audiological tests were performed, tinnitus parameters (frequency, intensity,
minimal masking levels, residual inhibition) were measured. After four weeks of
the treatment the questionnaires were repeated. RESULTS: Masking treatment for
tinnitus patients resulted with significant decrease in Tinnitus Handicap
Inventory and VAS scores. After four weeks of the masking treatment the
questionnaire was repeated. Twenty patients did not respond to treatment.
CONCLUSION: Masking therapy is one of the most effective methods of treatment for
tinnitus patients. Masking therapy, that is not invasive and cost-effective has
an important place in the treatment of tinnitus. Especially in a short time
provides a significant reduction in tinnitus parameters.
PMID- 29336125
TI - Association of Chronic Subjective Tinnitus with Neuro- Cognitive Performance.
AB - INTRODUCTION: Chronic subjective tinnitus is associated with cognitive
disruptions affecting perception, thinking, language, reasoning, problem solving,
memory, visual tasks (reading) and attention. OBJECTIVE: To evaluate existence of
any association between tinnitus parameters and neuropsychological performance to
explain cognitive processing. MATERIALS AND METHODS: Study design was
prospective, consisting 25 patients with idiopathic chronic subjective tinnitus
and gave informed consent before planning their treatment. Neuropsychological
profile included (i) performance on verbal information, comprehension, arithmetic
and digit span; (ii) non-verbal performance for visual pattern completion
analogies; (iii) memory performance for long-term, recent, delayed-recall,
immediate-recall, verbal-retention, visualretention, visual recognition; (iv)
reception, interpretation and execution for visual motor gestalt. Correlation
between tinnitus onset duration/ loudness perception with neuropsychological
profile was assessed by calculating Spearman's coefficient. RESULTS: Findings
suggest that tinnitus may interfere with cognitive processing especially
performance on digit span, verbal comprehension, mental balance, attention &
concentration, immediate recall, visual recognition and visual-motor gestalt
subtests. Negative correlation between neurocognitive tasks with tinnitus
loudness and onset duration indicated their association. Positive correlation
between tinnitus and visual-motor gestalt performance indicated the brain
dysfunction. CONCLUSION: Tinnitus association with non-auditory processing of
verbal, visual and visuo-spatial information suggested neuroplastic changes that
need to be targeted in cognitive rehabilitation.
PMID- 29336126
TI - Effects of Smoking on Eustachian Tube and Hearing.
AB - OBJECTIVE: The purpose of this study was to evaluate the effect of tobacco use on
the Eustachian tube and inner ear function. STUDY DESIGN: Case-control study.
SUBJECTS AND SETTINGS: Thirty-one nonsmoking volunteers and 34 smoking subjects
recruited in an University Hospital, submitted to an audiological evaluation
including pure tone audiometry, basal tympanogram, stapedial reflexes analysis,
and nine-step eustachian tube (ET) function test. RESULTS: Pure Tone Average
(PTA) threshold at all frequencies tested was 12.5 dB in smokers and 3.7 in
nonsmoking subjects. Nine smokers (27%) presented some degree of hearing loss
versus none in the nonsmoker group. Linear regression analysis showed a higher
degree of sensorineural hearing loss with age in smokers. Among the smokers, 20
subjects (59%) presented an impaired tubal function for the nine-step
inflation/deflation tympanometric test, while only 6 (19%) subjects in the group
of nonsmokers showed a tubal dysfunction. CONCLUSION: Tobacco use may reduce the
ability to hear, mainly causing a sensorineural hearing loss for higher
frequencies. We also found the presence of a high number of smokers suffering
from tubal dysfunction. This has an important clinical relevance, not only
because smoking increases the incidence of middle ear diseases, but also because
tubal dysfunction may cause nonspecific symptoms characterised by ear fullness
and difficulties in middle ear equalisation.
PMID- 29336127
TI - Popularity and Harms of Aural Foreign Bodies: A Descriptive Study of Patients in
Baqiyatallah University Hospital, Tehran, Iran.
AB - OBJECTIVE: To evaluate the prevalence of external ear complications among Iranian
aural foreign body users attending to otolaryngology clinic of our hospital.
METHODS: In this cross-sectional study patients attending to Otolaryngology
clinics of Baqiyatallah hospital were enrolled regardless of their age, gender
and reason of attending. Patients between 15 and 60 years of age were included in
the present study. Those with positive history of chronic ear diseases, ear
surgery, congenital ear disorders, trauma to ear or head and neck region or shock
wave trauma were excluded from the study. Demographic information as well as data
on chief complaint, educational level, frequency and type of used foreign body
and findings of physical examination and Otoscopy by a single otolaryngologist
were recorded in a predesigned checklist. RESULTS: Eventually 362 patients (232
male and 130 female) with a mean age of 40.32 +/- 16.90 years underwent analysis.
Of all patients 244 (67.2%) were using a kind of aural foreign body frequently
and Cotton bud was the most popular (63.5%) used foreign body among patients.
Drying ear canal was the most common (54.9%) reason of using AFBs among study
individuals followed by itching (29.5%) and pyorrhea (11.06%). Also 11 (4.5%)
patients were using AFBs as a habit with no specific reason. Itching was the most
prevalent symptom reported by both aural foreign body users (78%) and non-users
(45.5%); however it was significantly higher among AFB users (p = 0.026). Also
hearing loss was significantly more reported by AFB users (p = 0.033). A majority
of patients had normal physical examination in both AFB users and non-users
group. Inflammation of ear canal was significantly more detected in AFB users (p
= 0.004). In addition, rate of right ear wax impaction was higher among AFB users
(p = 0.016). CONCLUSION: In conclusion we realized that 67.2% of patients
attending to Otolaryngology clinic of our hospital were using a kind of aural
foreign bodies and itching was the most common chief complaint of these patients.
PMID- 29336128
TI - The Effect of PRP-enriched Gelfoam on Chronic Tympanic Membrane Perforation: A
Double-blind Randomized Clinical Trial.
AB - OBJECTIVE: To evaluate the effect of PRP-enriched gelfoam on the healing of
chronic TM perforation in comparison with gelfoam alone. METHODS: In this double
blind randomized clinical trial Patients with chronic tympanic membrane were
randomly allocated to two groups; intervention group underwent tympanoplasty with
platelet rich plasma (PRP)- enriched gel foams and control group underwent
operation with conventional gel foams alone. Patients information was recorded 4
and 12 months after surgery. RESULTS: Eventually 24 patients (12 males and 12
females) with a mean age of 43.33 +/- 12.34 years in intervention and 41.33 +/-
10.02 years in control group underwent analysis (p = 0.667). Complete TM healing
was seen in 8 (66.67%) patients in intervention group and 3 (25%) patients in
control group three months after intervention (p = 0.031, OR = 5.98). CONCLUSION:
Addition of PRP to conventional gelfoams used in TM perforation repair increases
the complete healing rate of TM perforation with less morbidity and
complications.
PMID- 29336129
TI - Somatic Tinnitus.
AB - Modulation of tinnitus characteristics such as pitch and loudness has been
extensively described following movements of the head, neck and limbs, vertical
or horizontal eye gaze, pressure on myofascial trigger points, cutaneous
stimulation of the hands, electrical stimulation of the median nerve, and
transcranial direct current stimulation. Modulation of tinnitus follows complex
interactions between auditory and somatosensory afferents and can be favored by
underlying somatic disorders. When tinnitus appears to be preceded or strictly
linked to a somatic disorder, and therefore related to problems of the
musculoskeletal system rather than of the ear, it is defined somatic tinnitus. A
correct diagnosis and treatment of somatic disorders underlying tinnitus play a
central role for a correct management of somatic tinnitus. However, the
identification of somatic tinnitus may be complex in some cases. In this paper,
after a general review of the current evidences for somatic tinnitus available in
the literature, we present and discuss some cases of patients in which somatic
modulation of tinnitus played a role-although different from case to case-in
their tinnitus, describing the diagnostic and therapeutic approaches followed in
each individual case and the results obtained, also highlighting unexpected
findings and pitfalls that may be encountered when approaching somatic tinnitus
patients.
PMID- 29336130
TI - Comparison of Three Types of Mesenchymal Stem Cells (Bone Marrow, Adipose Tissue,
and Umbilical Cord-Derived) as Potential Sources for Inner Ear Regeneration.
AB - In this review, we compared the potential of mesenchymal stem cells derived from
bone marrow, adipose tissue and umbilical cord as suitable sources for
regeneration of inner ear hair cells and auditory neurons. Our intensive
literature search indicates that stem cells in some of adult mammalian tissues,
such as bone marrow, can generate new cells under physiological and pathological
conditions. Among various types of stem cells, bone marrow-derived mesenchymal
stem cells are one of the most promising candidates for cell replacement therapy.
Mesenchymal stem cells have been reported to invade the damaged area, contribute
to the structural reorganization of the damaged cochlea and improve incomplete
hearing recovery. We suggest that bone marrow-derived mesenchymal stem cells
would be more beneficial than other mesenchymal stem cells.
PMID- 29336131
TI - Vestibular Schwannoma and Ipsilateral Endolymphatic Hydrops: An Unusual
Association.
AB - Vestibular schwannoma and endolymphatic hydrops are two conditions that may
present with similar audio-vestibular symptoms. The association of the two in the
same patient represents an unusual finding that may lead clinicians to errors and
delays in diagnosis and clinical management of affected subjects. We discuss the
case of a patient with an intrameatal vestibular schwannoma reporting symptoms
suggestive for ipsilateral endolymphatic hydrops. The patient presented with
fluctuating hearing loss, tinnitus, and acute rotatory vertigo episodes, and
underwent a full audiological evaluation and imaging of the brain with contrast
enhanced Magnetic Resonance Imaging. Clinical audio-vestibular and radiological
examination confirmed the presence of coexisting vestibular schwannoma and
endolymphatic hydrops. Hydrops was treated pharmacologically; vestibular
schwannoma was monitored over time with a wait and scan protocol through
conventional MRI. The association of vestibular schwannoma and endolymphatic
hydrops is rare, but represents a possible finding in clinical practice. It is
therefore recommended investigating the presence of inner ear disorders in
patients with vestibular schwannoma and, similarly, to exclude the presence of
this condition in patients with symptoms typical of inner ear disorders.
PMID- 29336132
TI - Auditory System Synchronization and Cochlear Function in Patients with Normal
Hearing With Tinnitus: Comparison of Multiple Feature with Longer Duration and
Single Feature with Shorter Duration Tinnitus.
AB - OBJECTIVE: To observe cochlear and brainstem function in normal hearing ears with
tinnitus using DPOAE and ABR audiometry. DESIGN: Case-control study. SAMPLE SIZE:
Included 60 normal hearing male patients with age less than 45 years; control
group consisted of 30 patients without tinnitus and the study group consisted of
those with unilateral tinnitus of at least 6 month duration. Pure tone
audiometry, tinnitus matching (pitch & loudness), DPOAE (SNR & Amplitude) and ABR
results of absolute latency of wave I, III and V, with IPL difference of I-III,
III-V & I-V, and ILD-V were investigated. RESULTS: SNR and amplitude value of
DPOAE were significantly different between tinnitus ears and without tinnitus
ears. Abnormal prolonged absolute latencies of peak I, III, V suggesting presence
of hearing loss above 8 kHz and significant difference of only IPL III-V in the
tinnitus ear suggesting of upper brain steam lesion in tinnitus patients were
found. The IPL of III-V and ILD-V findings were significantly different in longer
duration with multiple features (more than one type of pitch) than shorter
duration with single feature tinnitus. Thus whole brainstem function has
significant relationship with the presence of tinnitus, longer duration with
multiple nature of tinnitus perception. CONCLUSION: Abnormal OAE and ABR results
were present in patients with tinnitus. It was more prominent in patients with
longer duration with multiple features of tinnitus perception.
PMID- 29336133
TI - Effects of Tinnitus Retraining Therapy with Different Colours of Sound.
AB - BACKGROUND: In Tinnitus Retraining Therapy (TRT) sound stimulation is
conventionally performed with low-level broadband sound generators; since the
patient has to receive it for many hours in a day, it is important that the sound
is tolerable and agreeable to the patient. A clinical trial was undertaken to
evaluate the effect of different colour sound generators on tinnitus. The colour
of a sound refers to the power spectrum of the signal. The sound generators used
in this study provide the option to choose the preferred or most acceptable sound
among white, red and pink noise. METHODS AND FINDINGS: Changes in Tinnitus
Handicap Inventory and Numeric Rating Scales were measured in 20 patients after 3
and 6 months following the fitting of ear-level multi-colour sound generators.
The outcomes were compared to a similar group of 20 participants receiving the
same management except through conventional white noise sound generators.
Significant improvements were obtained in both groups following 3 and 6 months
after fitting. No significant difference was found between the two groups using
one or the other type of sound. Two thirds of the patient preferred white noise,
making it the most appealing amongst the options. The rest of the patients
indicated red noise as the preferred sound given that it reminded them of
soothing noises like shower or rainfall. No one chose pink noise. CONCLUSIONS:
TRT with different colour sound generators is effective in reducing the
discomfort caused by tinnitus in normal hearing patients. Enabling the patients
to choose their preferred sound after short trial periods achieved higher patient
satisfaction. This practice could help tailor individualized treatment for each
patient.
PMID- 29336134
TI - Treatment of Tinnitus: A Scoping Review.
AB - BACKGROUND: Tinnitus is a perception of an auditory sensation without the
presence of an external sound. It has devastating impact on the quality of life
and psychosocial aspect of the sufferer. Mechanisms of tinnitus not clear;
however, its management include counselling, hearing aids, tinnitus masking,
relaxation therapy, cognitive behaviour therapy and tinnitus retraining therapy.
OBJECTIVE: To conduct a scoping review to explore the role of counselling,
hearing aids, tinnitus masking, relaxation therapy, cognitive-behavioural therapy
and tinnitus retraining therapy in India. To also provide an overview of efficacy
of these approaches in tinnitus management. RESEARCH DESIGN: Scoping review.
STUDY SAMPLE: Experimental studies, follow-up assessments, and reviews assessing
tinnitus treatment approaches were identified as a result of an electronic
database met search. RESULTS: The evidence suggests that all tinnitus management
programs have their unique benefits in the treatment of tinnitus. Given the
confounding variables that include length of therapy, tinnitus severity and
subject population, the overall level of evidence is equivocal. Nonetheless, the
efficacy of CBT appears reasonably established and combined approach (masking +
counselling + attention diversion) appears to be most promising for audiologists
for future tinnitus management. A common ground of therapeutic elements was
established and evidence was found to be robust enough to guide clinical
practice. CONCLUSION: The use of more robust methodology with well-defined
control groups, as well as randomization of clinical trials in future studies
would increase the quality of evidence in the study of tinnitus management.
CLINICAL RECOMMENDATION: Combined therapies (masking + counselling + attention
diversion) appear more appropriate in the treatment of tinnitus as the evidence
is not sufficient to support a specific treatment method.
PMID- 29336135
TI - A Randomized, Placebo-Controlled, Double-Blind, Parallel Groups Study Evaluating
the Performance and Safety of a Steady State Coherent Biomodulator Patch in the
Treatment of Subjective Tinnitus.
AB - OBJECTIVE: The objectives of this study were to evaluate the performance and
safety of an innovative passive light photon driven microscopic biomodulator
patch as an alternative medical device for tinnitus relief. MATERIALS AND
METHODS: Eighty-two (82) patients were randomized to receive either an active
(biomodulator) patch or a placebo patch, for a 3-week treatment period. Patch
performance (evaluated with questionnaires related to tinnitus and quality-of
life) and safety were assessed after 3 weeks of treatment (Week 3) and at a
follow-up visit 4-weeks after end of treatment (Week 7). RESULTS: The
biomodulator patch was safe and well-tolerated and was efficacious, with
significant difference (p < 0.05) between the groups at Week 7; active patch had
30% responders compared to 10% for placebo, measured as a decrease from baseline
in at least 2 points in tinnitus annoyance visual analogue scale (VAS, 0-10).
Tinnitus handicap inventory (THI, 0-100) improved by mean -16 points
significantly (p = 0.0005) for the active responder group, but with no
statistically significant changes for the placebo group or between the groups.
Well-being questionnaire also improved for the active responder group, but not
statistically significant. The placebo responder group did not improve in well
being. Other tinnitus related symptoms did not show significant changes. There
was no statistically significant difference in performance between the active
(biomodulator) and placebo groups directly at the end of treatment (Week 3).
CONCLUSION: In a cost-risk-benefit rationale according to this study it can be
reasonable to recommend the biomodulator patch for treatment of tinnitus.
Improvements were shown at Week 7 (4 weeks after the end of treatment period).
PMID- 29336136
TI - International Clinical Protocol on Vestibular Disorders (Dizziness).
AB - 26-28 May at 43 Congress of Neurootological and Equilibriometric Society
(Budapest, Hungary) International Clinical Protocol on Vestibular Disorders
(Dizziness) being discussed and accepted as Consensus Document. Cochrane reports
estimates that dizziness has prevalence of 22.9% in the last 12 months and an
incidence of 3.1%. Only 1.8% of adults consulted a physician in the last 12
months. Cochrane reviews suggest that the evidence base for dizziness evaluation
is weak, thus necessitates the creation of evidence-based document. Protocol is
based at the new concept of vestibular system, which involves the vestibular
peripheral sensors, space orientation tetrad, vestibular presentations in the
brain cortex and vestibular effectory projections in the brain. Labyrinth
consists of sensors, for which six modalities are adequate: 1. acceleration, 2.
gravitation, 3. low frequency whole-body vibration, 4. Infrasound, 5. magnetic
impulse, 6. metabolic changes. Vestibular system from rhomboid fosse gets the
inputs from visual, acoustic, somatosensory organs, integrating them and forming
space perception and orientation. Interaction with space is realized through
sensory, motor, vegetative and limbic projections. So, vestibular disturbances
may manifest as paropsia, tinnitus, numbness. Vestibular evoked potentials (not
VEMP) and craniocorpography have highest sensitivity (90% and more). As
vestibular dysfunction has recurrent character patients need monitoring.
PMID- 29336137
TI - In Vitro Differentiation of Human Bone Marrow Mesenchymal Stem Cells to Hair
Cells Using Growth Factors.
AB - OBJECTIVE: In this study, we attempted to differentiated human bone marrow
derived mesenchymal stem cells (hBMSCs) to auditory hair cells using growth
factors. METHODS: Retinoic acid (RA), basic fibroblast growth factor (bFGF), and
epidermal growth factor (EGF) were added to hBMSCs cell culture medium. The cells
were evaluated morphologically and the expression of SOX2, POU4F3, MYO7A, and
Calretinin at mRNA level and ATOH1 mRNA and protein expression. RESULTS: After
treatment with the growth factors, the morphology of the cells did not change,
but evaluation of gene expression at the mRNA level increased the expression of
the ATOH1, SOX2, and POU4F3 markers. Growth factors increased the expression of
ATOH1 at the protein level. The expression of calretinin showed decreased and
MYO7A no significant change in expression. CONCLUSION: hBMSCs have the potential
to differentiate to hair cell-like using the RA, bFGF, and EGF.
PMID- 29336138
TI - Psycho acoustical Measures in Individuals with Congenital Visual Impairment.
AB - INTRODUCTION: In congenital visual impaired individuals one modality is impaired
(visual modality) this impairment is compensated by other sensory modalities.
There is evidence that visual impaired performed better in different auditory
task like localization, auditory memory, verbal memory, auditory attention, and
other behavioural tasks when compare to normal sighted individuals. OBJECTIVE:
The current study was aimed to compare the temporal resolution, frequency
resolution and speech perception in noise ability in individuals with congenital
visual impaired and normal sighted. METHODS: Temporal resolution, frequency
resolution, and speech perception in noise were measured using MDT, GDT, DDT,
SRDT, and SNR50 respectively. Twelve congenital visual impaired participants with
age range of 18 to 40 years were taken and equal in number with normal sighted
participants. All the participants had normal hearing sensitivity with normal
middle ear functioning. RESULTS: Individual with visual impairment showed
superior threshold in MDT, SRDT and SNR50 as compared to normal sighted
individuals. This may be due to complexity of the tasks; MDT, SRDT and SNR50 are
complex tasks than GDT and DDT. CONCLUSION: Visual impairment showed superior
performance in auditory processing and speech perception with complex auditory
perceptual tasks.
PMID- 29336139
TI - Smart Self-Assembled Nanosystem Based on Water-Soluble Pillararene and Rare-Earth
Doped Upconversion Nanoparticles for pH-Responsive Drug Delivery.
AB - Exploring novel drug delivery systems with good stability and new structure to
integrate pillararene and upconversion nanoparticles (UCNPs) into one system
continues to be an important challenge. Herein, we report a novel preparation of
a supramolecular upconversion nanosystem via the host-guest complexation based on
carboxylate-based pillar[5]arene (WP5) and 15-carboxy-N,N,N-trialkylpentadecan-1
ammonium bromide (1)-functionalized UCNPs to produce WP5?1-UCNPs that can be
loaded with the chemotherapeutic drug doxorubicin (DOX). Importantly, the WP5 on
the surface of the drug-loaded nanosystem can be efficiently protonated under
acidic conditions, resulting in the collapse of the nanosystem and drug release.
Moreover, cellular uptake confirms that the nanosystem can enter human cervical
cancer (HeLa) cells, resulting in drug accumulation in the cells. More
importantly, cytotoxicity experiments demonstrated the excellent biocompatibility
of WP5?1-UCNPs without loading DOX and that the nanosystem DOX-WP5?1-UCNPs
exhibited an ability of killing HeLa cells effectively. We also investigated
magnetic resonance imaging and upconversion luminescence imaging, which may be
employed as visual imaging agents in cancer diagnosis and treatment. Thus, in the
present work, we show a simple yet powerful strategy to combine UCNPs and
pillar[5]arene to produce a unified nanosystem for dual-mode bioimaging-guided
therapeutic applications.
PMID- 29336140
TI - Synthesis of Cisplatin(IV) Prodrug-Tethered CuFeS2 Nanoparticles in Tumor
Targeted Chemotherapy and Photothermal Therapy.
AB - In this study, for the first time, CuFeS2 nanocrystals were successfully prepared
through a facile noninjection-based synthetic strategy, by reacting Cu and Fe
precursors with dodecanethiol in a 1-octadecene solvent. This one-pot
noninjection strategy features easy handling, large-scale production, and high
synthetic reproducibility. Following hyaluronic acid (HA) encapsulation, CuFeS2
nanocrystals coated with HA (CuFeS2@HA) not only readily dispersed in water and
showed improved biocompatibility but also possessed a tumor-specific targeting
ability of cancer cells bearing the cluster determinant 44 (CD44) receptors. The
encapsulated CuFeS2@HA showed broad optical absorbance from the visible to the
near-infrared (NIR) region and high photothermal conversion efficiencies of about
74.2%. They can, therefore, be utilized for the photothermal ablation of cancer
cells with NIR light irradiation. In addition, toxicity studies in vitro (B16F1
and HeLa) and in vivo (zebrafish embryos), as well as in vitro blood
compatibility studies, indicated that CuFeS2@HA show low cytotoxicity at the
doses required for photothermal therapy. More importantly, CuFeS2@HA can be used
as delivery vehicles for chemotherapy cisplatin(IV) prodrug forming CuFeS2@HA
Pt(IV). Their release profile revealed pH- and glutathione-mediated drug release
from CuFeS2@HA-Pt(IV), which may minimize the side effects of the drug to normal
tissues during therapy. Subsequent in vitro experiments confirmed that the use of
CuFeS2@HA-Pt(IV) provides an enhanced and synergistic therapeutic effect compared
to that from the use of either chemotherapy or photothermal therapy alone.
PMID- 29336141
TI - Label-Free Optical Biodetection of Pathogen Virulence Factors in Complex Media
Using Microtoroids with Multifunctional Surface Functionality.
AB - Early detection of pathogens or their virulence factors in complex media has a
key role in early diagnosis and treatment of many diseases. Nanomolar and
selective detection of Exotoxin A, which is a virulence factor secreted from
Pseudomonas aeruginosa in the sputum of Cystic Fibrosis (CF) patients, can pave
the way for early diagnosis of P. aeruginosa infections. In this study, we
conducted a preliminary study to demonstrate the feasibility of optical
biodetection of P. aeruginosa Exotoxin A in a diluted artificial sputum mimicking
the CF respiratory environment. Our surface engineering approach provides an
effective biointerface enabling highly selective detection of the Exotoxin A
molecules in the complex media using monoclonal anti-Exotoxin A functionalized
microtoroids. The highly resilient microtoroid surface toward other constituents
of the sputum provides Exotoxin A detection ability in the complex media by
reproducible measurements. In this study, the limit-of-detection of Exotoxin A in
the complex media is calculated as 2.45 nM.
PMID- 29336142
TI - Smart Dual Quenching Strategy Enhances the Detection Sensitivity of Intracellular
Furin.
AB - Development of sensitive fluorescence "Turn-On" strategies for imaging enzyme
activity in living cells is of disease-diagnostic importance but remains
challenging. Herein, by employing a click condensation reaction and rational
design of a single quenched probe Cys(StBu)-Lys(Gly-Lys(DABCYL)-Gly-Gly-Arg-Arg
Val-Arg-Gly-FITC)-CBT (1), we developed a "smart" dual quenching strategy and
applied it to detect intracellular furin activity with enhanced sensitivity. At
physiological conditions, 1 was subjected to reduction-controlled condensation
reaction to form 1-NPs and its fluorescence intensity further dropped to 1/2.8 of
its original. Upon furin cleavage in vitro, the dual quenched 1-NPs had
fluorescence "Turn-On" contrast 11-fold more than that of single quenched control
probe FITC-Gly-Arg-Val-Arg-Arg-Gly-Gly-Lys(DABCYL)-Gly-OH (1-P). Live cell
imaging results indicated that 1 showed fluorescence "Turn-On" contrast 6.3-fold
of that of 1-P for sensing intracellular furin activity. We envision that, by
replacing the RVRR substrate with other enzyme-cleavable ones, our versatile
"smart" dual quenching strategy could be easily adjusted for the detection (or
imaging) of other intracellular enzymes' activity with enhanced sensitivity.
PMID- 29336143
TI - Water-Soluble Fluorescent Probe with Dual Mitochondria/Lysosome Targetability for
Selective Superoxide Detection in Live Cells and in Zebrafish Embryos.
AB - A novel water-soluble fluorescein-based fluorescent probe for superoxide
detection was developed. The probe is fairly stable under neutral and acidic
conditions. It can be used to detect superoxide both in solution with the
detection limit of 2.2 MUM and in living cells. Cell imaging experiments
indicated that such a probe displayed good cell penetration and O2*- could be
detected with PMA-stimulated HepG2 cells in both mitochondria and lysosome. Such
a probe is the first dual mitochondria- and lysosome- targetable fluorescent
chemodosimeter. Additionally, O2*- in intact live zebrafish embryos was
successfully visualized under PMA-stimulated conditions, and the possible
detection mechanism was studied as well.
PMID- 29336144
TI - Nanostructured Peptidotoxins as Natural Pro-Oxidants Induced Cancer Cell Death
via Amplification of Oxidative Stress.
AB - Melittin (Mel), one of the host defense peptides derived from the venom of
honeybees, demonstrates substantial anticancer properties, which is attributed to
augmenting reactive oxygen species (ROS) generation. However, little has been
reported on its pro-oxidation capacity in cancer oxidation therapy. In this
study, an ROS amplifying nanodevice was fabricated through direct complexation of
two natural pro-oxidants, Mel and condensed epigallocatechin gallate (pEGCG). The
obtained nanocomplex (NC) was further covered with phenylboronic acid derivatized
hyaluronic acid (pHA) through the ROS-responsive boronate ester coordination bond
to produce pHA-NC. Upon undergoing receptor-mediated endocytosis into cancer
cells, the inner cores of pHA-NC will be partially uncovered once pHA corona is
degraded by hyaluronidase and will then escape from the lysosome by virtue of
cytolytic Mel. The elevated ROS level in the tumor cytoplasm can disrupt the
boronate ester bond to facilitate drug release. Both Mel and pEGCG could
synergistically amplify oxidative stress and prolong ROS retention in cancer
cells, leading to enhanced anticancer efficacy. This ROS cascade amplifier based
on selective coordination bond and inherent pro-oxidation properties of natural
ingredients could detect and elevate intracellular ROS signals, potentiating to
move the tumor away from its homeostasis and make the tumor vulnerable. Compared
to previously reported chemosynthetic pro-oxidants, the ROS self-sufficient
system, fully composed of natural medicine, from this study provides a new
insight in developing cancer oxidation therapy.
PMID- 29336145
TI - T1-Mediated Nanosensor for Immunoassay Based on an Activatable MnO2 Nanoassembly.
AB - Current magnetic relaxation switching (MRS) sensors for detection of trace
targets in complex samples still suffer from limitations in terms of relatively
low sensitivity and poor stability. To meet this challenge, we develop a
longitudinal relaxation time (T1)-based nanosensor by using Mn2+ released from
the reduction of a MnO2 nanoassembly that can induce the change of T1, and thus
can greatly improve the sensitivity and overcome the "hook effect" of
conventional MRS. Through the specific interaction between antigen and the
antibody-functionalized MnO2 nanoassembly, the T1 signal of Mn2+ released from
the nanoassembly is quantitatively determined by the antigen, which allows for
highly sensitive and straightforward detection of targets. This approach broadens
the applicability of magnetic biosensors and has great potential for applications
in early diagnosis of disease biomarkers.
PMID- 29336146
TI - Coordination-Triggered Hierarchical Folate/Zinc Supramolecular Hydrogels Leading
to Printable Biomaterials.
AB - Printable hydrogels desired in bioengineering have extremely high demands on
biocompatibility and mechanic strength, which can hardly be achieved in
conventional hydrogels made with biopolymers. Here, we show that on employment of
the strategy of coordination-triggered hierarchical self-assembly of naturally
occurring small-molecule folic acid, supramolecular hydrogels with robust
mechanical elastic modulus comparable to synthetic double-network polymer gels
can be made at concentrations below 1%. A sequence of hierarchical steps are
involved in the formation of this extraordinary hydrogel: petrin rings on folate
form tetramers through hydrogen bonding, tetramers stack into nanofibers by pi-pi
stacking, and zinc ions cross-link the nanofibers into larger-scale fibrils and
further cross-link the fibril network to gel water. These supramolecular
qualities endow the hydrogel with shear-thinning and instant healing ability,
which makes the robust gel injectable and printable into various three
dimensional structures. Owing to the excellent biocompatibility, the gel can
support cells three-dimensionally and can be used as an ideal carrier for imaging
agent (Gd3+), as well as chemodrugs. In combination with its easy formation and
abundant sources, this newly discovered metallo-folate supramolecular hydrogel is
promising in various bioengineering technological applications.
PMID- 29336147
TI - Urolithins Attenuate LPS-Induced Neuroinflammation in BV2Microglia via MAPK, Akt,
and NF-kappaB Signaling Pathways.
AB - Emerging data suggest that urolithins, gut microbiota metabolites of
ellagitannins, contribute toward multiple health benefits attributed to
ellagitannin-rich foods, including walnuts, red raspberry, strawberry, and
pomegranate. However, there is limited data on whether the potential
neuroprotective effects of these ellagitannin-rich foods are mediated by
urolithins. Herein, we evaluated the potential mechanisms of
antineuroinflammatory effects of urolithins (urolithins A, B, and C; 8-methyl-O
urolithin A; and 8,9-dimethyl-O-urolithin C) in BV2 murine microglia in vitro.
Nitrite analysis and qRT-PCR suggested that urolithins A and B reduced NO levels
and suppressed mRNA levels of pro-inflammatory genes of TNF-alpha, IL-6, IL
1beta, iNOS, and COX-2 in LPS-treated microglia. Western blot revealed that
urolithins A and B decreased phosphorylation levels of Erk1/2, p38 MAPK, and Akt,
prevented IkappaB-alpha phosphorylation and degradation, and inhibited NF-kappaB
p65 subunit phosphorylation and nuclear translocation in LPS-stimulated
microglia. Our results indicated that urolithins A and B attenuated LPS-induced
inflammation in BV2 microglia, which may be mediated by inhibiting NF-kappaB,
MAPKs (p38 and Erk1/2), and Akt signaling pathway activation. The
antineuroinflammatory activities of urolithins support their role in the
potential neuroprotective effects reported for ellagitannin-rich foods warranting
further in vivo studies on these ellagitannin gut microbial derived metabolites.
PMID- 29336148
TI - Logic Catalytic Interconversion of G-Molecular Hydrogel.
AB - By incorporating hemin into G-quadruplex (G4) during cation-templated self
assembly between guanosine and KB(OH)4, we have constructed an artificial enzyme
hydrogel (AEH)-based system for the highly sensitive and selective detection of
Pb2+. The sensing strategy is based on a Pb2+-induced decrease in AEH activity.
Because of the higher efficiency of Pb2+ for stabilizing G4 compared with K+, the
Pb2+ ions substitute K+ and trigger hemin release from G4, thus giving rise to a
conformational interconversion accompanied by the loss of enzyme activity. The
Pb2+-induced catalytic interconversion endows the AEH-based system with high
sensitivity and selectivity for detecting Pb2+. As a result, the AEH-based system
shows an excellent response for Pb2+ in the range from 1 pM to 50 nM with a limit
of detection of ~0.32 pM, which is much lower than that of the previously
reported G4-DNAzyme. We also demonstrate that this AEH-based system exhibits high
selectivity toward Pb2+ over other metal ions. Furthermore, two two-input INHIBIT
logic gates have been constructed via switching of the catalytic interconversion
induced by K+ and Pb2+ or K+ and pH. Given its versatility, this AEH-based system
provides a novel platform for sensing and biomolecular computation.
PMID- 29336149
TI - Molecular Imprinting Based Hybrid Ratiometric Fluorescence Sensor for the Visual
Determination of Bovine Hemoglobin.
AB - We describe a simple and effective strategy to construct a molecular imprinting
ratiometric fluorescence sensor (MIR sensor) for the visual detection of bovine
hemoglobin (BHb) used as a model protein. The sensor was prepared by simply
mixing the solution of green and red CdTe quantum dots (QDs), which were embedded
in core-shell structured molecularly imprinted polymers and silica nanoparticles,
respectively. The resultant hybrid MIR sensor can selectively bind with BHb and
thus quench the fluorescence of the green QDs, while the red QDs wrapped with
silica are insensitive to BHb with the fluorescence intensity unchanged. As a
result, a continuous obvious fluorescence color change from green to red can be
observed by naked eyes, with the detection limit of 9.6 nM. Moreover, the MIR
sensor was successfully applied to determine BHb in bovine urine samples with
satisfactory recoveries at three spiking levels ranging from 95.7 to 101.5%,
indicating great potential application for detecting BHb in real samples. This
strategy of using different fluorescence emission materials incorporated to
construct a ratiometric fluorescence sensor is reasonable and convenient, which
can be extended to the preparation of other ratiometric fluorescence systems for
targeted analytes.
PMID- 29336150
TI - Chemical Exchange Saturation Transfer in Chemical Reactions: A Mechanistic Tool
for NMR Detection and Characterization of Transient Intermediates.
AB - The low sensitivity of NMR and transient key intermediates below detection limit
are the central problems studying reaction mechanisms by NMR. Sensitivity can be
enhanced by hyperpolarization techniques such as dynamic nuclear polarization or
the incorporation/interaction of special hyperpolarized molecules. However, all
of these techniques require special equipment, are restricted to selective
reactions, or undesirably influence the reaction pathways. Here, we apply the
chemical exchange saturation transfer (CEST) technique for the first time to NMR
detect and characterize previously unobserved transient reaction intermediates in
organocatalysis. The higher sensitivity of CEST and chemical equilibria present
in the reaction pathway are exploited to access population and kinetics
information on low populated intermediates. The potential of the method is
demonstrated on the proline-catalyzed enamine formation for unprecedented in situ
detection of a DPU stabilized zwitterionic iminium species, the elusive key
intermediate between enamine and oxazolidinones. The quantitative analysis of
CEST data at 250 K revealed the population ratio of [Z-iminium]/[exo
oxazolidinone] 0.02, relative free energy +8.1 kJ/mol (calculated +7.3 kJ/mol),
and free energy barrier of +45.9 kJ/mol (DeltaG?calc.(268 K) = +42.2 kJ/mol) for
Z-iminium -> exo-oxazolidinone. The findings underpin the iminium ion
participation in enamine formation pathway corroborating our earlier theoretical
prediction and help in better understanding. The reliability of CEST is validated
using 1D EXSY-build-up techniques at low temperature (213 K). The CEST method
thus serves as a new tool for mechanistic investigations in organocatalysis to
access key information, such as chemical shifts, populations, and reaction
kinetics of intermediates below the standard NMR detection limit.
PMID- 29336152
TI - Mutation of Phenylalanine-223 to Leucine Enhances Transformation of
Benzo[a]pyrene by Ring-Hydroxylating Dioxygenase of Sphingobium sp. FB3 by
increasing Accessibility of the Catalytic Site.
AB - Burning of agricultural biomass generates polycyclic aromatic hydrocarbons (PAHs)
including the carcinogen benzo[a]pyrene, of which the catabolism is primarily
initiated by a ring-hydroxylating dioxygenase (RHD). This study explores
catalytic site accessibility and its role in preferential catabolism of some PAHs
over others. The genes flnA1f, flnA2f, flnA3, and flnA4, encoding the oxygenase
alpha and beta subunits, ferredoxin, and ferredoxin reductase, respectively, of
the RHD enzyme complex (FlnA) were cloned from Sphingobium sp. FB3 and
coexpressed in E. coli BL21. The FlnA effectively transformed fluoranthene but
not benzo[a]pyrene. Substitution of the bulky phenylalanine-223 by leucine
reduces the steric constraint in the substrate entrance to make the catalytic
site of FlnA more accessible to large substrates, as visualized by 3D modeling,
and allows the FlnA mutant to efficiently transform benzo[a]pyrene. Accessibility
of the catalytic site to PAHs is a mechanism of RHD substrate specificity. The
results shed light on why some PAHs are more recalcitrant than others.
PMID- 29336151
TI - Ultrarobust Biochips with Metal-Organic Framework Coating for Point-of-Care
Diagnosis.
AB - Most biosensors relying on antibodies as recognition elements fail in harsh
environment conditions such as elevated temperatures, organic solvents, or
proteases because of antibody denaturation, and require strict storage conditions
with defined shelf life, thus limiting their applications in point-of-care and
resource-limited settings. Here, a metal-organic framework (MOF) encapsulation is
utilized to preserve the biofunctionality of antibodies conjugated to
nanotransducers. This study investigates several parameters of MOF coating
(including growth time, surface morphology, thickness, and precursor
concentrations) that determine the preservation efficacy against different
protein denaturing conditions in both dry and wet environments. A plasmonic
biosensor based on gold nanorods as the nanotransducers is employed as a model
biodiagnostic platform. The preservation efficacy attained through MOF
encapsulation is compared to two other commonly employed materials (sucrose and
silk fibroin). The results show that MOF coating outperforms sucrose and silk
fibroin coatings under several harsh conditions including high temperature (80
degrees C), dimethylformamide, and protease solution, owing to complete
encapsulation, stability in wet environment and ease of removal at point-of-use
by the MOF. We believe this study will broaden the applicability of this
universal approach for preserving different types of on-chip biodiagnostic
reagents and biosensors/bioassays, thus extending the benefits of advanced
diagnostic technologies in resource-limited settings.
PMID- 29336153
TI - Genetic Algorithm Based Design and Experimental Characterization of a Highly
Thermostable Metalloprotein.
AB - The development of thermostable and solvent-tolerant metalloproteins is a long
sought goal for many applications in synthetic biology and biotechnology. In this
work, we were able to engineer a highly thermostable and organic solvent-stable
metallo variant of the B1 domain of protein G (GB1) with a tetrahedral zinc
binding site reminiscent of the one of thermolysin. Promising candidates were
designed computationally by applying a protocol based on classical and first
principles molecular dynamics simulations in combination with genetic algorithm
optimization. The most promising of the computationally predicted mutants was
expressed and structurally characterized and yielded a highly thermostable
protein. The experimental results thus confirm the predictive power of the
applied computational protein engineering approach for the de novo design of
highly stable metalloproteins.
PMID- 29336154
TI - Methods for Determining Cell Wall-Bound Phenolics in Maize Stem Tissues.
AB - We compared two methods with different sample pretreatment, hydrolysis, and
separation procedures to extract cell wall-bound phenolics. The samples were pith
and rind tissues from six maize inbred lines reportedly containing different
levels of cell wall-bound phenolics. In method 1, pretreated samples were
extracted with a C18 solid-phase extraction cartridge, and it took 6 days to
complete. In method 2, phenolics were extracted from crude samples with ethyl
acetate, it took 2 days to complete, and the cost per sample was reduced more
than 60%. Both methods extracted more 4-coumarate than ferulate. Overall, method
1 yielded more 4-coumarate, while method 2 yielded more ferulate. The lack of a
genotype * method interaction and significant correlations between the results
obtained using the two methods indicate that both methods are reliable for use in
large-scale plant breeding programs. Method 2, scaled, is proposed for general
plant biology research.
PMID- 29336155
TI - Highly Bendable Flexible Perovskite Solar Cells on a Nanoscale Surface Oxide
Layer of Titanium Metal Plates.
AB - We report highly bendable and efficient perovskite solar cells (PSCs) that use
thermally oxidized layer of Ti metal plate as an electron transport layer (ETL).
The power conversion efficiency (PCE) of flexible PSCs reaches 14.9% with a short
circuit current density (Jsc) of 17.9 mA/cm2, open-circuit voltage (Voc) of 1.09,
and fill factor (ff) of 0.74. Moreover, the Ti metal-based PSCs exhibit a
superior fatigue resistance over indium tin oxide/poly(ethylene terephthalate)
substrate. Flexible PSCs maintain 100% of their initial PCE even after PSCs are
bent 1000 times at a bending radius of 4 mm. This excellent performance of
flexible PSCs is due to high crystalline quality and low oxygen vacancy
concentration of TiO2 layer. The concentration of oxygen vacancies in the
oxidized Ti metal surface controls the electric function of TiO2 as ETL of PSCs.
A decrease in the oxygen vacancy concentration of the TiO2 layer is critical to
improving the electron collection efficiency of the ETL. Our results suggest that
Ti metal-based PSCs possess excellent mechanical properties, which can be applied
to the renewable energy source for flexible electronics.
PMID- 29336156
TI - Infrared Dielectric Screening Determines the Low Exciton Binding Energy of Metal
Halide Perovskites.
AB - The performance of lead-halide perovskites in optoelectronic devices is due to a
unique combination of factors, including highly efficient generation, transport,
and collection of photogenerated charge carriers. The mechanism behind efficient
charge generation in lead-halide perovskites is still largely unknown. Here, we
investigate the factors that influence the exciton binding energy (Eb) in a
series of metal-halide perovskites using accurate first-principles calculations
based on solution of the Bethe-Salpeter equation, coupled to ab initio molecular
dynamics simulations. We find that Eb is strongly modulated by screening from low
energy phonons, which account for a factor ~2 Eb reduction, while dynamic
disorder and rotational motion of the organic cations play a minor role. We
calculate Eb = 15 meV for MAPbI3, in excellent agreement with recent experimental
estimates. We then explore how different material combinations (e.g., replacing
Pb -> Pb:Sn-> Sn; and MA -> FA -> Cs) may lead to different Eb values and
highlight the mechanisms underlying Eb tuning.
PMID- 29336157
TI - Glycerol Hydrogen-Bonding Network Dominates Structure and Collective Dynamics in
a Deep Eutectic Solvent.
AB - The deep eutectic solvent glyceline formed by choline chloride and glycerol in
1:2 molar ratio is much less viscous compared to glycerol, which facilitates its
use in many applications where high viscosity is undesirable. Despite the large
difference in viscosity, we have found that the structural network of glyceline
is completely defined by its glycerol constituent, which exhibits complex
microscopic dynamic behavior, as expected from a highly correlated hydrogen
bonding network. Choline ions occupy interstitial voids in the glycerol network
and show little structural or dynamic correlations with glycerol molecules.
Despite the known higher long-range diffusivity of the smaller glycerol species
in glyceline, in applications where localized dynamics is essential (e.g., in
microporous media), the local transport and dynamic properties must be dominated
by the relatively loosely bound choline ions.
PMID- 29336159
TI - Ligand-Controlled Copper(I)-Catalyzed Cross-Coupling of Secondary and Primary
Alcohols to alpha-Alkylated Ketones, Pyridines, and Quinolines.
AB - One hexanuclear Cu(I) cluster of 4,6-dimethylpyrimidine-2-thiolate efficiently
catalyzes the dehydrogenative cross-coupling of secondary and primary alcohols to
alpha-alkylated ketones with high selectivity. This transformation proceeds
through a one-pot sequence of dehydrogenation of alcohols, condensation of
aldehydes and ketones, hydrogenation of the resulting alpha,beta-unsaturated
ketones, and dehydrogenation of the alpha-alkylated alcohols to generate alpha
alkylated ketones. This catalytic system also displays high activity for the
annulation reaction of secondary alcohols with gamma-amino- and 2-aminobenzyl
alcohols to yield pyridines and quinolines, respectively.
PMID- 29336158
TI - Chromosome Gene Orientation Inversion Networks (GOINs) of Plasmodium Proteome.
AB - The spatial distribution of genes in chromosomes seems not to be random. For
instance, only 10% of genes are transcribed from bidirectional promoters in
humans, and many more are organized into larger clusters. This raises intriguing
questions previously asked by different authors. We would like to add a few more
questions in this context, related to gene orientation inversions. Does gene
orientation (inversion) follow a random pattern? Is it relevant to biological
activity somehow? We define a new kind of network coined as the gene orientation
inversion network (GOIN). GOIN's complex network encodes short- and long-range
patterns of inversion of the orientation of pairs of gene in the chromosome. We
selected Plasmodium falciparum as a case of study due to the high relevance of
this parasite to public health (causal agent of malaria). We constructed here for
the first time all of the GOINs for the genome of this parasite. These networks
have an average of 383 nodes (genes in one chromosome) and 1314 links (pairs of
gene with inverse orientation). We calculated node centralities and other
parameters of these networks. These numerical parameters were used to study
different properties of gene inversion patterns, for example, distribution, local
communities, similarity to Erdos-Renyi random networks, randomness, and so on. We
find clues that seem to indicate that gene orientation inversion does not follow
a random pattern. We noted that some gene communities in the GOINs tend to group
genes encoding for RIFIN-related proteins in the proteome of the parasite. RIFIN
like proteins are a second family of clonally variant proteins expressed on the
surface of red cells infected with Plasmodium falciparum. Consequently, we used
these centralities as input of machine learning (ML) models to predict the RIFIN
like activity of 5365 proteins in the proteome of Plasmodium sp. The best linear
ML model found discriminates RIFIN-like from other proteins with sensitivity and
specificity 70-80% in training and external validation series. All of these
results may point to a possible biological relevance of gene orientation
inversion not directly dependent on genetic sequence information. This work opens
the gate to the use of GOINs as a tool for the study of the structure of
chromosomes and the study of protein function in proteome research.
PMID- 29336160
TI - Visible-Light Photoredox/Nickel Dual Catalysis for the Cross-Coupling of Sulfinic
Acid Salts with Aryl Iodides.
AB - An efficient cross-coupling of sodium or lithium sulfinates with aryl iodides,
using a combination of nickel and photoredox catalysis, is described. The dual
catalyst system enables a versatile synthesis of aryl sulfones at room
temperature in good yields and displays a broad functional group compatibility.
The potential utility of this method in the late-stage diversification of complex
molecules and in the conversion of organolithium reagents and sulfur dioxide into
sulfones is demonstrated.
PMID- 29336161
TI - Stereoselective Synthesis of 1,4,5-Tri-cis-guaiane Sesquiterpene: First Total
Synthesis of (-)-Dendroside C Aglycon.
AB - The first total synthesis of (-)-dendroside C aglycon, consisting of a 1,4,5-tri
cis-guaiane skeleton, from a versatile hydroazulene intermediate has been
accomplished. The key features of the syntheses include the stereoselective
preparation of the unusual cis-hydroazulene core via a sequence of a unique
Dieckmann condensation of the bicyclic lactone system, which was concisely
prepared by the tandem conjugate addition and intramolecular allylic alkylation
of a butenolide precursor, and construction of the characteristic tricyclic
skeleton by a carbene-mediated cyclopropanation.
PMID- 29336162
TI - Regioselective Synthesis of alpha- and gamma-Amino Quinolinyl Phosphonamides
Using N-Heterocyclic Phosphines (NHPs).
AB - A regioselective phosphonylation of quinolines for the synthesis of alpha-amino
quinolinyl phosphonamides and gamma-amino quinolinyl phosphonamides has been
developed under mild reaction conditions. An NHP-thiourea enables selective
synthesis of alpha-amino quinolinyl phosphonamides by a Reissert-type reaction,
and an NHP-tosylamide affords gamma-amino quinolinyl phosphonamides via a 1,4
conjugate addition reaction. The corresponding amino quinolinyl phosphonate
adducts were obtained in moderate to excellent yields (up to 99% yield) and
regioselectivities (up to 99:1) with good functional group tolerance.
PMID- 29336163
TI - Construction of Polycyclic Indole Derivatives via Multiple Aryne Reactions with
Azaheptafulvenes.
AB - An efficient [8 + 2]/aryl-ene tandem reaction between azaheptafulvenes and arynes
has been developed, leading to the formation of cyclohepta[b]indoles in a single
step with good yield. In addition, employment of excess arynes provides a [8 +
2]/aryl-ene /[6 + 2] tandem reaction to synthesize polycyclic
oxacyclohepta[b]indoles. This is the first time that azaheptafulvenes have been
employed in tandem reactions with arynes.
PMID- 29336164
TI - Management of Takayasu arteritis.
PMID- 29336165
TI - Development of novel delivery system for nanoencapsulation of catalase:
formulation, characterization, and in vivo evaluation using oxidative skin injury
model.
AB - One of the main challenges for successful pharmaceutical application of Catalase
(CAT) is maintaining its stability. Physical immobilization of CAT through nano
encapsulation was proposed to resolve this challenge. CAT encapsulating niosomes
(e-CAT) were prepared using Brij(r) 30, 52, 76, 92, and 97 in the presence of
cholesterol (Ch) by thin film hydration method. Niosomes were characterized for
encapsulation efficiency % (EE), size, poly-dispersity index (PI), and
morphology. Kinetic parameters, pH optimum, thermal stability, and reusability of
CAT were determined. The influence of optimized e-CAT dispersion onto thermally
injured rat skin was evaluated. Results revealed that encapsulation enhanced CAT
catalytic efficiency (Vmax/Km). Free CAT and e-CAT had pH optimum at 7.0. e-CAT
exhibited improved thermal stability where it retained 50% residual activity at
60 degrees C. Free CAT lost its activity after three consecutive operational
cycles; however, e-CAT retained 60% of its initial activity following 12 cycles.
After 24 h of topical application on thermal injury, a significant difference in
lesion size was observed with e-CAT compared with the control group. Based on
these encouraging results, CAT immobilization demonstrated a promising novel
delivery system that enhances its operational stability. In addition, nano
encapsulated CAT can be anticipated to be beneficial in skin oxidative injury.
PMID- 29336166
TI - Optimizing outcomes in EGFR mutation-positive NSCLC: which tyrosine kinase
inhibitor and when?
AB - Despite the efficacy of standard-of-care EGFR tyrosine kinase inhibitors (TKIs),
erlotinib, gefitinib and afatinib, in EGFR mutation-positive non-small-cell lung
cancer, resistance develops, most commonly due to the T790M mutation. Osimertinib
showed clinical activity in the treatment of T790M-positive disease following
progression on a first-line TKI, and is approved in this setting. Recently,
osimertinib improved efficacy versus first-generation TKIs (erlotinib and
gefitinib) in the first-line setting. Multiple factors can influence first-line
treatment decisions, including subsequent therapy options, presence of brain
metastases and tolerability, all of which should be considered in the long-term
treatment plan. Further research into treatment sequencing is also needed, to
optimize outcomes in EGFR mutation-positive non-small-cell lung cancer.
PMID- 29336167
TI - Does personal experience of dementia change attitudes? The Bristol and South
Gloucestershire survey of dementia attitudes.
AB - Background It is unclear how attitudes towards people with dementia are formed
and whether, for instance, increased contact with people with dementia, either
through work or personal experience alters attitudes. This study used a validated
questionnaire (the Approaches to Dementia Questionnaire) to examine whether
having experience of dementia (either as a result of work, or by being affected
by dementia) is associated with differences in attitudes towards dementia.
Methods A modified version of the Approaches to Dementia Questionnaire was
completed by 2201 participants, either online or in written form. Participants
also recorded their age, gender and ethnicity as well as whether they worked with
people with dementia or had been personally affected by dementia. Results
Increased contact with people with dementia was associated with increases in both
total Approaches to Dementia Questionnaire scores and across both sub-scales
reflecting more positive person-centred attitudes toward dementia. The highest
levels of increase were found amongst non-white participants. Conclusions This
study is, we believe, the first attempt to look systematically at whether greater
contact with people with dementia is associated with changes in attitudes. The
results strongly support the contention that increased contact with people with
dementia leads to more person-centred attitudes, and by inference, less
stigmatising views.
PMID- 29336168
TI - Dementia in Eastern Mediterranean countries: A systematic review.
AB - Globally, there is an increase in the older population, whose lives are affected
by local cultural norms. In Eastern Mediterranean countries, dementia is
conventionally hidden from view with few dedicated services or recognition for
diagnosis. The aim of this systematic review is to explore the limited literature
on dementia and cognitive impairment among older people in Eastern Mediterranean
countries to present an evaluation of current practices and to consolidate
knowledge for future planning. Thirty-three studies were identified for inclusion
in the review, and four themes were apparent. Firstly, prevalence, comorbidity
and gender: In Eastern Mediterranean countries, many studies identify that the
prevalence of dementia is high. As is the case elsewhere, many older adults in
Eastern Mediterranean countries have at least one coexisting long-term condition,
and some experience low life-satisfaction. Secondly, culture: In Eastern
Mediterranean countries, the older adult is highly respected, and placement
outside of the family home is considered an abandonment of family duty. The term
dementia carries stigma, and it is widely believed that dementia is caused by
'fate'. Thirdly, recognition and tools: There is a lack of verified assessment
instruments to assess for dementia. Despite concerns about the cultural
appropriateness of the Mini-Mental State Exam, particularly for people who have
low literacy levels, and low literacy being the norm in Eastern Mediterranean
countries, the Mini-Mental State Examination is the main assessment instrument.
Translation and transition of non-Arabic assessment instruments and tools with
psychometric properties presents a challenge for clinicians. Finally, workforce
issues: health care workers lack knowledge about dementia, as dementia care is a
relatively recent addition to the nursing and medical syllabi. While there were
some inconsistencies in the papers published, many of the articles call for
increasing educational programmes and health and social care policies to promote
improved and practical gerontological nursing and medicine. Health care
professionals need education about sociocultural, religious, and language needs
to deliver improved culturally sensitive care.
PMID- 29336169
TI - Bone metastasis target redox-responsive micell for the treatment of lung cancer
bone metastasis and anti-bone resorption.
AB - In order to inhibit the growth of lung cancer bone metastasis and reduce the bone
resorption at bone metastasis sites, a bone metastasis target micelle DOX@DBMs
ALN was prepared. The size and the zeta potential of DOX@DBNs-ALN were about 60
nm and -15 mV, respectively. DOX@DBMs-ALN exhibited high binding affinity with
hydroxyapatite and released DOX in redox-responsive manner. DOX@DBMs-ALN was
effectively up taken by A549 cells and delivered DOX to the nucleus of A549
cells, which resulted in strong cytotoxicity on A549 cells. The in vivo
experimental results indicated that DOX@DBMs-ALN specifically delivered DOX to
bone metastasis site and obviously prolonged the retention time of DOX in bone
metastasis site. Moreover, DOX@DBMs-ALN not only significantly inhibited the
growth of bone metastasis tumour but also obviously reduced the bone resorption
at bone metastasis sites without causing marked systemic toxicity. Thus, DOX@DBMs
ALN has great potential in the treatment of lung cancer bone metastasis.
PMID- 29336170
TI - Nanoparticles for treatment of atherosclerosis: challenges of plasmonic
photothermal therapy in translational studies.
PMID- 29336171
TI - Phenolic composition, antioxidant and antinociceptive activities of Syringa
vulgaris L. bark and leaf extracts.
AB - Metabolite profile, antioxidant and antinociceptive activities of Syringa
vulgaris bark and leaf methanolic extracts were investigated. By means of HPLC
DAD-ESI-TOF and HPLC-DAD-ESI-MS/MS, a total of 33 phenolics were identified,
including 15 secoiridoids, 6 phenylpropanoids, 3 flavonoids, 3 lignans and 6 low
molecular weight phenols. Validated quantitative analysis show that syringin
(2.52%) and rutin (1.13%) are the main phenolic compounds in bark and leaf,
respectively. Notable radical scavenging and antinociceptive activities of the
bark and leaf extracts were confirmed by in vitro DPPH? and ABTS?+ assays and by
in vivo hot-plate method in mice, respectively. Our results could lay the
scientific basic of future clinical perspectives of lilac bark and leaf.
PMID- 29336172
TI - Correction to: Erci et al., Green synthesis of silver nanoparticles using Thymbra
spicata L. var. spicata (zahter) aqueous leaf extract and evaluation of their
morphology-dependent antibacterial and cytotoxic activity.
PMID- 29336173
TI - Genome analysis and clinical implications of the bacterial communities in early
biofilm formation on dental implants restored with titanium or zirconia
abutments.
AB - This cross-sectional study aimed to identify and quantify up to 42 target species
colonizing the early biofilm of dental implants restored with titanium or
zirconia abutments. A total of 720 samples from 20 healthy individuals were
investigated. Biofilm samples were collected from the peri-implant sulci, inner
parts of implants, abutment surfaces and prosthetic crowns over a functioning
period of 30 days. Checkerboard DNA-DNA hybridization was used for microbial
detection and quantitation. Clinical characteristics (probing depth, bleeding on
probing, clinical attachment level and marginal bone loss) were also investigated
during the monitoring period. Genome counts were low at the implant loading time
point for both the abutment materials, and increased over time. Both the titanium
and the zirconia groups presented similar microbial counts and diversity over
time, and the microbiota was very similar to that colonizing the remaining teeth.
Clinical findings were consistent with a healthy condition with no significant
difference regarding marginal bone loss between the two materials.
PMID- 29336174
TI - Modularising outpatient care delivery: A mixed methods case study at a Finnish
University Hospital.
AB - BACKGROUND: Modularisation is a potential means to develop health care delivery
by combining standardisation and customisation. However, little is known about
the effects of modularisation on hospital care. The objective was to analyse how
modularisation may change and support health care delivery in specialised
hospital care. METHODS: A mixed methods case study methodology was applied using
both qualitative and quantitative data, including interviews, field notes,
documents, service usage data, bed count and personnel resource data. Data from a
reference hospital's unit were used to understand the context and development of
care delivery in general. RESULTS: The following outcome themes were identified
from the interviews: balance between demand and supply; support in shift from
inpatient to outpatient care; shorter treatment times and improved management of
service production. Modularisation supported the shift from inpatient towards
outpatient care. Changes in resource efficiency measures were both positive and
negative; the number of patients per personnel decreased, while the number of
visits per personnel and the bed utilisation rate increased. CONCLUSIONS:
Modularisation may support health care providers in classifying patients and
delivering services according to patients' needs. However, as the findings are
based on a single university hospital case study, more research is needed.
PMID- 29336175
TI - A new monoterpene from the poisonous mushroom Trogia venenata, which has caused
Sudden Unexpected Death in Yunnan province, China.
AB - A new monoterpene, 6,7,8-trihydroxy-2,6-dimethyloctanoic acid (1), and a known
sesquiterpene, beta-caryophyllene 4R,5R-oxide (2), as well as four known ergosta
steroids, 5alpha,8alpha-epidioxyergosta-6,22-dien-3beta-y1 linoleate (3), 3-O
beta-D-glucopyranosyl-22E,24R-5alpha,8alpha-epidioxyergosta-6,22-dien (4),
5alpha,8alpha-epidioxy-(22E,24R)-ergosta-6,22-dien-3beta-ol (5) and (22E,24R)
ergosta-7,22-dien-3beta-ol (6), were isolated from the fruiting bodies of the
mushroom Trogia venenata. The structures of these compounds were identified by
the analysis of spectral data. All of the compounds were isolated from this
mushroom for the first time.
PMID- 29336176
TI - Replenishing the damaged heart with oxygen by nature-inspired photosynthesis.
PMID- 29336177
TI - In vivo assessment of a nanofibrous silk tube as nerve guide for sciatic nerve
regeneration.
AB - A nanofibrous silk nerve conduit has been evaluated for its efficiency based on
the promotion of peripheral nerve regeneration in rats. The designed tubes with
or without Schwann cells were implanted into a 10 mm gap in the sciatic nerves of
the rats. Four months after the surgery, the regenerated nerves were monitored
and evaluated by macroscopic assessments and histology. The results demonstrated
that the nanofibrous grafts, especially in the presence of Schwann cells, enabled
reconstruction of the rat sciatic nerve trunk with a restoration of nerve
continuity and formation of nerve fibres with myelination. Histological data
demonstrated the presence of Schwann and glial cells in regenerated nerves. This
study strongly supports the feasibility of using artificial nerve grafts for
peripheral nerve regeneration by bridging large defects in a rat model.
PMID- 29336178
TI - Evaluation of take-home exposure to asbestos from handling asbestos-contaminated
worker clothing following the abrasive sawing of cement pipe.
AB - Although industrial uses of asbestos have declined since the 1970s, in recent
years there has been a renewed interest in para-occupational ("take-home")
exposure to these fibers. The aim of this study was to quantify the release of
asbestos fibers, if any, during the shaking out of crocidolite- and chrysotile
contaminated clothing in a simulated at-home setting. An exposure study was
conducted in which personal and area air samples were collected during the
handling (i.e. shake-out) of work clothing (shirt and pants) previously worn by
an operator who had cut asbestos-containing cement pipe. During eight "loading"
events, the operator cut a historically representative asbestos-containing cement
pipe (10% crocidolite and 25% chrysotile) using a powered abrasive saw.
Subsequently, 30-minute air samples were collected during four "shake-out"
events, each of which consisted of the handling of two complete sets of
contaminated work clothes. Samples were analyzed in accordance with NIOSH methods
7400 and 7402. The mean phase contrast microscopy equivalent (PCME) airborne
concentrations were 0.52 f/cc (SD = 0.34 f/cc) for total asbestos fibers, 0.36
f/cc (SD = 0.26 f/cc) for chrysotile and 0.17 f/cc (SD = 0.096 f/cc) for
crocidolite. Based on likely estimates of the frequency of laundering activities,
and assuming that the dusty clothing (1) is not blown off in the occupational
setting using compressed air and (2) is not shaken out before entering the home,
a family member handling the clothing could potentially have a lifetime
cumulative exposure to chrysotile and crocidolite of approximately 0.20 f/cc-year
and 0.096 f/cc-year, respectively.
PMID- 29336180
TI - Erratum.
PMID- 29336179
TI - Belimumab and antipneumococcal vaccination in patients with systemic lupus
erythematosus.
AB - In systemic lupus erythematosus (SLE), flares can be caused by infections. In
particular, Streptococcus pneumoniae infection can be severe or even potentially
lethal in absence of previous immunization or in case of 'aggressive' systemic
antibiotic therapy. Immunization efficacy, however, can be reduced in such
patients with the use of the various immunosuppressive therapeutic regimens. In
particular, the use of novel monoclonal antibodies against B lymphocytes raises
concerns over the potential interference with antipneumococcal vaccination.
Previous studies demonstrated that belimumab therapy did not significantly reduce
the efficacy of antipneumococcal vaccination, when received after the initiation
of belimumab therapy. The study being evaluated in this article investigated the
efficacy of vaccination in relationship to initiation of belimumab therapy in SLE
patients.
PMID- 29336181
TI - Analytical and between-subject variation of thrombin generation measured by
calibrated automated thrombography on plasma samples.
AB - BACKGROUND: The Calibrated Automated Thrombography (CAT) is an in vitro thrombin
generation (TG) assay that holds promise as a valuable tool within clinical
diagnostics. However, the technique has a considerable analytical variation, and
we therefore, investigated the analytical and between-subject variation of CAT
systematically. Moreover, we assess the application of an internal standard for
normalization to diminish variation. METHODS: 20 healthy volunteers donated one
blood sample which was subsequently centrifuged, aliquoted and stored at -80
degrees C prior to analysis. The analytical variation was determined on eight
runs, where plasma from the same seven volunteers was processed in triplicates,
and for the between-subject variation, TG analysis was performed on plasma from
all 20 volunteers. The trigger reagents used for the TG assays included both PPP
reagent containing 5 pM tissue factor (TF) and PPPlow with 1 pM TF. Plasma, drawn
from a single donor, was applied to all plates as an internal standard for each
TG analysis, which subsequently was used for normalization. RESULTS: The total
analytical variation for TG analysis performed with PPPlow reagent is 3-14% and 9
13% for PPP reagent. This variation can be minimally reduced by using an internal
standard but mainly for ETP (endogenous thrombin potential). The between-subject
variation is higher when using PPPlow than PPP and this variation is considerable
higher than the analytical variation. CONCLUSION: TG has a rather high inherent
analytical variation but considerable lower than the between-subject variation
when using PPPlow as reagent.
PMID- 29336182
TI - The effects of fermented milk containing Lactococcus lactis subsp. cremoris FC on
defaecation in healthy young Japanese women: a double-blind, placebo-controlled
study.
AB - The objective of this double-blind, placebo-controlled study was to elucidate the
effects of fermented milk containing Lactococcus lactis subsp. cremoris FC (FC)
on defaecation in healthy young women. We included 31 women (18-31 years old) who
were randomly selected into two groups. Subjects in the test group consumed
fermented milk containing FC, while subjects in the placebo group consumed non
fermented gelled milk. In the test group, defaecation frequency (both in days and
times per week) and stool volume significantly increased during the consumption
of fermented milk containing FC compared with before consumption. These effects
were also observed in subjects with mild constipation. Furthermore, in subjects
with mild constipation, stool ammonia concentration was significantly lower in
the test group than that in the placebo group after 4 weeks. These results
suggest that fermented milk containing FC is beneficial for improving defaecation
and faecal properties.
PMID- 29336183
TI - Postradiation Synovial Sarcoma of the Common Bile Duct: A Previously Unreported
Anatomic Site.
AB - Synovial sarcoma is a ubiquitous neoplasm predominantly affecting soft tissues of
young adults of any gender; few cases have been described in the digestive
system, mostly in the stomach. The (X;18)(p11.2; q11.2) translocation yields
unique SS18-SSX fusion genes. Synovial sarcoma has been related to radiotherapy,
but no synovial sarcoma has been associated with the digestive system. This
article describes the case of a synovial sarcoma arising along the extrahepatic
biliary tree, 10 years after the application of an abdominal radiotherapy
schedule due to a retroperitoneal metastatic seminoma in a male who developed
progressive obstructive jaundice. Ninety percent of the analyzed cells carried
the SS18 gene with separation of sequences, thus denoting a translocation. There
are only 8 post-radiotherapy synovial sarcomas that have been reported
previously, and this is the first report of a radiotherapy-related synovial
sarcoma arising from the extrahepatic biliary tree, and the second case described
in this anatomic region.
PMID- 29336184
TI - Alpha-amylase, alpha-glucosidase and lipase inhibiting activities of polyphenol
rich extracts from six common bean cultivars of Southern Italy, before and after
cooking.
AB - Common beans (Phaseolus vulgaris) are a good source of nutrients and phenolic
compounds with versatile health benefits. Polyphenol-rich extracts of six
ecotypes of P. vulgaris were analysed to determine their phenolic profiles and
assayed in vitro for inhibitory effects on digestive enzymes relevant to
carbohydrates and lipids metabolism. The extracts inhibited enzyme activities in
a dose-dependent manner. IC 50 values ranged from 69 +/- 1.9 to 126 +/- 3.2
MUg/mL and from 107.01 +/- 4.5 to 184.20 +/- 5.7 MUg/mL, before and after
cooking, for alpha-amylase, from 39.3 +/- 4.4 to 74.13 +/- 6.9 MUg/mL and from 51
+/- 7.7 to 122.1 +/- 5.2 MUg/mL for alpha-glucosidase and from 63.11 +/- 7.5 to
103.2 +/- 5.9 MUg/mL and from 92.0 +/- 6.3 to 128.5 +/- 7.4 MUg/mL for lipase.
Results suggest encouraging their consumption, being natural sources of enzyme
inhibitors important for type-2 diabetes and obesity prevention/control. Well
monitored in vivo studies would help to establish their beneficial effects,
making them worthwhile of further consideration as functional foods.
PMID- 29336185
TI - An update on first line therapies for metastatic breast cancer.
AB - INTRODUCTION: In recent years, outcomes of patients with metastatic breast cancer
(MBC) have improved due to a greater understanding of the mechanisms of
carcinogenesis in the development of newer molecularly targeted drugs, especially
those as a front-line therapy. Remarkable improvements have been made in the
treatment of hormone receptor positive (HR+) and Her2 positive MBC and currently
targeted treatment strategies represent a valid first line treatment. Areas
covered: Herein, the authors provide an overview of the first-line
pharmacotherapies currently available for the treatment of MBC and provide their
expert perspectives on the area. Expert opinion: Decisions on the first-line
treatment of MBC should consider the clinical features of the disease, but also
the biological mechanisms that regulate tumor cell growth. New and effective
therapeutic agents have recently been introduced in the first-line therapy of
MBC. However, to optimize the treatment of patients with metastatic disease,
clinicians need biomarkers of resistance or sensitivity to targeted therapies.
Efforts must also be made in developing strategies to personalize treatments of
MBC patients and to identify those patients who might gain the most benefit from
new treatment interventions, to save costs and limit toxicity.
PMID- 29336186
TI - Subcutaneous Fat Necrosis of Newborn: Unfamiliar Histomorphology of a Familiar
Lesion.
PMID- 29336187
TI - Efficacy and safety of sirukumab in Japanese patients with moderate to severe
rheumatoid arthritis inadequately controlled by disease modifying anti-rheumatic
drugs: Subgroup analysis of a phase 3 study.
AB - OBJECTIVE: To evaluate the efficacy and safety of sirukumab in Japanese patients
with active rheumatoid arthritis (RA) uncontrolled by disease-modifying
antirheumatic drugs. METHODS: This subgroup analysis based on a double-blind,
placebo-controlled, 52-week phase 3 study (SIRROUND-D) assessed American College
of Rheumatology (ACR) 20 response at week 16 and van der Heijde-modified Sharp
score (vdH-S) at week 52 (coprimary endpoints). RESULTS: A total of 168
(Japanese)/1670 patients received sirukumab 50 mg/4 weeks (q4w, n = 58), 100
mg/every 2 weeks (q2w, n = 54), or placebo (n = 56) subcutaneously. Significantly
more patients achieved ACR20 response at week 16 with sirukumab (50 mg q4w:
69.0%; 100mg q2w: 66.7%) vs. placebo (21.4%; p < .001). Median change from
baseline in total vdH-S score at week 52 was significantly lower with sirukumab
(50 mg q4w: 0.3, p = .024; 100 mg q2w: 0.0, p = .002) vs. placebo (1.3).
Sirukumab consistently showed greater improvements in secondary endpoints at
weeks 24 and 52. Nasopharyngitis, elevated liver enzymes, injection site erythema
and upper respiratory tract infections were the common treatment-emergent adverse
events (TEAEs). Incidences of TEAEs and serious AEs were consistent between
sirukumab groups through week 52. CONCLUSION: Sirukumab showed clinically
meaningful improvements consistent with significant improvements in the global
study. No new safety signals were observed.
PMID- 29336188
TI - Establishment of reference interval for the tumour marker serum CYFRA 21-1 in
healthy Chinese Han ethnic adults.
AB - BACKGROUND: Our aim was to establish the reference interval (RI) for serum CYFRA
21-1 in healthy Chinese Han ethnic adults, since there has been no report about
it. METHODS: After screening, 9954 healthy Chinese Han adults (age range 18-95
years) were recruited, including 6639 (66.7%) males and 3315 (33.3%) females.
Electrochemiluminescence immunoassay was used to measure serum CYFRA21-1. The RI
was defined by nonparametric 95% percentile interval. RESULTS: The distribution
for serum CYFRA21-1 level was non-Gaussian. The RI for healthy Chinese Han adults
calculated by nonparametric method was 0-4.47 ng/ml in this study, higher than
that recommended by Roche Diagnostics GmbH (<=3.3 ng/ml). The reference values
were higher in males than females before 50 years of age, although the difference
was hardly seen after 50 years of age. The reference value increased with age in
both males and females. Of slight difference, the increase of male reference
value was obvious at 60-69 and more than 80 years of age, while that of female
obvious at 50-69 and more than 80 years of age. CONCLUSIONS: We establish the RI
for serum CYFRA21-1 in healthy Chinese Han population, which is higher than that
recommended by Roche Diagnostics GmbH. Furthermore, our study suggests that it is
necessary to establish the age- and sex-specific RIs for serum CYFRA21-1.
PMID- 29336189
TI - Depression, sexual satisfaction, and other psychological issues in women with
polycystic ovary syndrome.
AB - Polycystic ovary syndrome (PCOS) increases the risk of depression, poor quality
of life, and low sexual satisfaction of women. The aim of the study was to
evaluate the prevalence of these disorders and to assess the need for
psychological consultation at the time of PCOS diagnosis. A case-control single
center study of 250 women who were diagnosed with PCOS voluntarily filled in an
anonymous, interactive questionnaire. The inquiry form included 27 questions
covering the woman's characteristics, satisfaction with their outer appearance
and sexual life, as well as the Beck Depression Inventory (BDI). Based on the
BDI, 52% (130/250) of studied women presented depressive symptoms. This group had
significantly higher body mass index (29.5 +/- 8.1 vs. 24.6 +/- 5.8; p<.001) and
a lower level of self-attractiveness than other studied women (3.3 +/- 2.2 vs.
5.4 +/- 2.3; p<.001). Forty two percent (106/250) of women viewed themselves as
unattractive. A correlation between reduced sexual satisfaction and a sense of
low attractiveness was noted (r = 0.465, p<.001). Sixty four percent (160/250) of
women believed that psychological consultation should be offered to all PCOS
women. Treatment of PCOS women should be multidisciplinary and include
psychological counseling, especially in obese PCOS women with inadequate family
support and dissatisfied with their sexual life.
PMID- 29336190
TI - A cost-effectiveness analysis of calcipotriol plus betamethasone dipropionate
aerosol foam versus gel for the topical treatment of plaque psoriasis.
AB - BACKGROUND: Calcipotriol 50 ug/g and betamethasone 0.5 mg/g dipropionate (Cal/BD)
aerosol foam formulation provides greater effectiveness and improved patient
preference compared with traditional Cal/BD formulations for the topical
treatment of plaque psoriasis. OBJECTIVE: To determine the cost-effectiveness of
Cal/BD foam compared with Cal/BD gel from the Australian perspective. METHODS: A
Markov model was developed to evaluate the cost-effectiveness of topical Cal/BD
foam and gel for the treatment of people with plaque psoriasis. Treatment
effectiveness, safety, and utilities were based on a randomized control trial,
resource use was informed by expert opinion, and unit costs were obtained from
public sources. Outcomes were reported in terms of 1-year costs, quality-adjusted
life years, and incremental cost-effectiveness ratios. All costs were reported in
2017 Australian Dollars. RESULTS: The model showed that patients using Cal/BD
foam had more QALYs and higher costs over 1 year compared with patients using
Cal/BD gel, resulting in a cost of $13,609 per QALY gained at 4-weeks. When 4
weeks of Cal/BD foam was compared with 8 weeks of Cal/BD gel treatment, Cal/BD
foam was $8 less expensive and resulted in 0.006 more QALYs gained. Sensitivity
analyses showed that, compared with Cal/BD ointment, Cal/BD foam was associated
with an incremental cost of $15,091 per QALY gained. CONCLUSION: Cal/BD foam is
the most cost-effective Cal/BD formulation for the topical treatment of patients
with plaque psoriasis.
PMID- 29336191
TI - Teratogenic potential of nanoencapsulated vitamin A evaluated on an alternative
model organism, the tunicate Ciona intestinalis.
AB - Nano-encapsulation is a technology used to pack substances in order to enhance
their stability and bioavailability, but this packing may interact with living
systems, causing unexpected toxicity. Vitamin A (vit A) is a substance that has
received attention, because in developed countries, the increasing availability
of supplements is leading to its excessive intake. This study aims to compare
teratogenic effects caused by exposure to the traditional formulation of vit A
versus nano-encapsulated vit A. We used ascidian embryos as an alternative model.
Ascidians are marine organisms closely related to vertebrates that share with
them a body plan and developmental programme, including the morphogenetic role of
retinoic acid (RA). Our data showed that the adverse effects of exposure to the
same concentration of the two formulations were different, suggesting that the
nano-encapsulation increased the bioavailability of the molecule, which could be
better absorbed and metabolised to RA, the effective teratogenic substance.
PMID- 29336192
TI - How mass spectrometric approaches applied to bacterial identification have
revolutionized the study of human gut microbiota.
AB - INTRODUCTION: Describing the human hut gut microbiota is one the most exciting
challenges of the 21st century. Currently, high-throughput sequencing methods are
considered as the gold standard for this purpose, however, they suffer from
several drawbacks, including their inability to detect minority populations. The
advent of mass-spectrometric (MS) approaches to identify cultured bacteria in
clinical microbiology enabled the creation of the culturomics approach, which
aims to establish a comprehensive repertoire of cultured prokaryotes from human
specimens using extensive culture conditions. Areas covered: This review first
underlines how mass spectrometric approaches have revolutionized clinical
microbiology. It then highlights the contribution of MS-based methods to
culturomics studies, paying particular attention to the extension of the human
gut microbiota repertoire through the discovery of new bacterial species. Expert
commentary: MS-based approaches have enabled cultivation methods to be
resuscitated to study the human gut microbiota and thus to fill in the blanks
left by high-throughput sequencing methods in terms of culturing minority
populations. Continued efforts to recover new taxa using culture methods,
combined with their rapid implementation in genomic databases, would allow for an
exhaustive analysis of the gut microbiota through the use of a comprehensive
approach.
PMID- 29336193
TI - Enhancement of iodinin solubility by encapsulation into cyclodextrin
nanoparticles.
AB - Phenazine is known to regroup planar nitrogen-containing heterocyclic compounds.
It was used here to enhance the bioavailability of the biologically important
compound iodinin, which is near insoluble in aqueous solutions. Its water
solubility has led to the development of new formulations using diverse
amphiphilic alpha-cyclodextrins (CDs). With the per-[6-desoxy-6-(3
perfluorohexylpropanethio)-2,3-di-O-methyl]-alpha-CD, we succeeded to get iodinin
loaded nanoformulations with good parameters such as a size of 97.9 nm, 62%
encapsulation efficiency and efficient control release. The study presents an
interesting alternative to optimizing the water solubility of iodinin by chemical
modifications of iodinin.
PMID- 29336194
TI - A Robust Multiplex Mass Spectrometric Assay for Screening Small-Molecule
Inhibitors of CD73 with Diverse Inhibition Modalities.
AB - CD73/Ecto-5'-nucleotidase is a membrane-tethered ecto-enzyme that works in tandem
with CD39 to convert extracellular adenosine triphosphate (ATP) into adenosine.
CD73 is highly expressed on various types of cancer cells and on infiltrating
suppressive immune cells, leading to an elevated concentration of adenosine in
the tumor microenvironment, which elicits a strong immunosuppressive effect. In
preclinical studies, targeting CD73 with anti-CD73 antibody results in favorable
antitumor effects. Despite initial studies using antibodies, inhibition of CD73
catalytic activity using small-molecule inhibitors may be more effective in
lowering extracellular adenosine due to better tumor penetration and
distribution. To screen small-molecule libraries, we explored multiple
approaches, including colorimetric and fluorescent biochemical assays, and due to
some limitations with these assays, we developed a mass spectrometry (MS)-based
assay. Only the MS-based assay offers the sensitivity and dynamic range required
for screening small-molecule libraries at a substrate concentration close to the
Km value of substrate and for evaluating the mode of binding of screening hits.
To achieve a throughput suitable for high-throughput screening (HTS), we
developed a RapidFire-tandem mass spectrometry (RF-MS/MS)-based multiplex assay.
This assay allowed a large diverse compound library to be screened at a speed of
1536 reactions per 40-50 min.
PMID- 29336195
TI - Is aspiration and sclerotherapy treatment for hydroceles in the aging male an
evidence-based treatment?
AB - Symptomatic hydroceles are commonly treated with surgical repair. They are
associated with sexual dysfunction in the aging male. Patients who are not fit
for surgery often undergo aspiration and sclerotherapy of the hydrocele. There is
a range of sclerosing agents used in the literature. I performed a literature
search to assess whether one sclerosant was better than the others. STDS is the
sclerosing agent with the best cure rate after a single injection and low side
effect rates. The cure rates of sodium tetradecyl sulphate (STDS) after a single
aspiration and injection were 76%. After multiple treatments 94% achieved a cure.
Patient satisfaction rates at mean 40 months were 95%. Complication rates were
generally low and much lower than surgical repair. Aspiration and sclerotherapy
have a role in treating symptomatic hydroceles. This literature review shows that
this is over and above its current use in the UK, where it is used for patients
unfit for general anaesthetic. If the patients are carefully selected for this
procedure, they can have a good outcome and avoid the higher complication rate
and longer recovery rates of surgical repair. Patients should be counselled about
aspiration and sclerotherapy as part of the informed consent process.
PMID- 29336196
TI - Effect of Chromoendoscopy Filters on Visualization of KTP Laser-Associated Tissue
Changes: A Cadaveric Animal Model.
AB - Standard KTP laser (potassium titanyl phosphate) wavelength-specific protective
eyewear often impairs visualization of tissue changes during laser treatment.
This sometimes necessitates eyewear removal to evaluate tissue effects, which
wastes time and poses safety concerns. The objective was to determine if
"virtual" or "electronic" chromoendoscopy filters, as found on some endoscopy
platforms, could alleviate the restricted visualization inherent to protective
eyewear. A KTP laser was applied to porcine laryngeal tissue and recorded via
video laryngoscopy with 1 optical (Olympus Narrow Band Imaging) and 8 digital
(Pentax Medical I-scan) chromoendoscopy filters. Videos were viewed by 11
otolaryngologists wearing protective eyewear. Using a discrete visual analog
scale, they rated each filter on its ability to improve visualization,. No filter
impaired visualization; 5 of 9 improved visualization. Based on statistical
significance, the number of positive responses, and the lack of negative
responses, narrow band imaging and the I-scan tone enhancement filter for
leukoplakia performed best. These filters could shorten procedure time and
improve safety; therefore, further clinical evaluation is warranted.
PMID- 29336198
TI - Long non-coding RNA GPR65-1 is up-regulated in gastric cancer and promotes tumor
growth through the PTEN-AKT-slug signaling pathway.
AB - Increasing evidence has shown that abnormal expression of lncRNAs is involved in
various biological behaviors and major cellular pathways of human cancers.
However, the role of lncRNAs in the progression of gastric cancer has not been
adequately investigated. Therefore, in this study, we investigated the expression
levels of linc-GPR65-1 using Quantitative real-time PCR (qRT-PCR) and found that
linc-GPR65-1 was significantly up-regulated in 50 gastric cancer tissues compared
to the corresponding normal tissues. In addition, increased linc-GPR65-1
expression was associated with TNM stage (P = 0.037), tumor size (P = 0.024),
distal metastasis (P = 0.023), and poor prognosis of gastric cancer patients.
Moreover, functional assays indicated that decreased linc-GPR65-1 expression
inhibited the aggressive phenotypes of gastric cancer cells, and enhanced linc
GPR65-1 expression resulted in the opposite phenomenon. Then, a cancer signaling
phosphoantibody microarray was conducted to explore the potential mechanisms of
linc-GPR65-1 in regulating gastric cancer progression and observed that linc
GPR65-1 could regulate the PTEN-AKT-slug signaling pathway. These data showed
that linc-GPR65-1, regulating the PTEN-AKT-slug signaling pathway, might act as a
tumor promoter and serve as a novel target for gastric cancer prevention and
therapy.
PMID- 29336197
TI - Neurosensory Deficits Vary as a Function of Point of Care in Pediatric Mild
Traumatic Brain Injury.
AB - Neurosensory abnormalities are frequently observed following pediatric mild
traumatic brain injury (pmTBI) and may underlie the expression of several common
concussion symptoms and delay recovery. Importantly, active evaluation of
neurosensory functioning more closely approximates real-world (e.g., physical and
academic) environments that provoke symptom worsening. The current study
determined whether symptom provocation (i.e., during neurosensory examination)
improved classification accuracy relative to pre-examination symptom levels and
whether symptoms varied as a function of point of care. Eighty-one pmTBI were
recruited from the pediatric emergency department (PED; n = 40) or outpatient
concussion clinic (n = 41), along with matched (age, sex, and education) healthy
controls (HC; n = 40). All participants completed a brief (~ 12 min) standardized
neurosensory examination and clinical questionnaires. The magnitude of symptom
provocation upon neurosensory examination was significantly higher for concussion
clinic than for PED patients. Symptom provocation significantly improved
diagnostic classification accuracy relative to pre-examination symptom levels,
although the magnitude of improvement was modest, and was greater in the
concussion clinic. In contrast, PED patients exhibited worse performance on
measures of balance, vision, and oculomotor functioning than the concussion
clinic patients, with no differences observed between both samples and HC.
Despite modest sample sizes, current findings suggest that point of care
represents a critical but highly under-studied variable that may influence
outcomes following pmTBI. Studies that rely on recruitment from a single point of
care may not generalize to the entire pmTBI population in terms of how
neurosensory deficits affect recovery.
PMID- 29336199
TI - The Rust Fungus Melampsora larici-populina Expresses a Conserved Genetic Program
and Distinct Sets of Secreted Protein Genes During Infection of Its Two Host
Plants, Larch and Poplar.
AB - Mechanisms required for broad-spectrum or specific host colonization of plant
parasites are poorly understood. As a perfect illustration, heteroecious rust
fungi require two alternate host plants to complete their life cycles. Melampsora
larici-populina infects two taxonomically unrelated plants, larch, on which
sexual reproduction is achieved, and poplar, on which clonal multiplication
occurs, leading to severe epidemics in plantations. We applied deep RNA
sequencing to three key developmental stages of M. larici-populina infection on
larch: basidia, pycnia, and aecia, and we performed comparative transcriptomics
of infection on poplar and larch hosts, using available expression data. Secreted
protein was the only significantly overrepresented category among differentially
expressed M. larici-populina genes between the basidial, the pycnial, and the
aecial stages, highlighting their probable involvement in the infection process.
Comparison of fungal transcriptomes in larch and poplar revealed a majority of
rust genes were commonly expressed on the two hosts and a fraction exhibited host
specific expression. More particularly, gene families encoding small secreted
proteins presented striking expression profiles that highlight probable candidate
effectors specialized on each host. Our results bring valuable new information
about the biological cycle of rust fungi and identify genes that may contribute
to host specificity.
PMID- 29336200
TI - Does CPAP Affect Patient-Reported Voice Outcomes?
AB - Upper aerodigestive tract symptoms are common in patients with obstructive sleep
apnea (OSA). It remains unclear whether continuous positive airway pressure
(CPAP) improves or worsens these otolaryngology symptoms. As therapy-related side
effects limit CPAP adherence, this study aimed to determine if CPAP negatively
affects voice, sinonasal, and reflux symptoms of the upper airway. Case series
with planned data collection was performed at an academic otolaryngology sleep
center. Newly diagnosed patients with OSA were evaluated before and 6 months
after initiating CPAP therapy. Data collected included CPAP data download, Reflux
Symptom Index (RSI), Epworth Sleepiness Scale (ESS), Voice Handicap Index 10 (VHI
10), Sino-Nasal Questionnaire (SNQ), and oral dryness visual analog scale (VAS).
For the 11 CPAP-adherent participants, the RSI significantly improved with CPAP
(mean RSI, 22.0-9.5; P = .002); however, the VAS, VHI-10, and SNQ did not change
after 6 months of CPAP therapy. In a small sample size, patient-reported voice
outcomes (VHI-10) and other upper aerodigestive tract symptoms did not worsen
with CPAP; rather, CPAP therapy was associated with a reduction in reflux
symptoms.
PMID- 29336201
TI - Poor Motor-Function Recovery after Spinal Cord Injury in Anxiety-Model Mice with
Phospholipase C-Related Catalytically Inactive Protein Type 1 Knockout.
AB - Mice with a knockout of phospholipase C (PLC)-related inactive protein type 1
(PRIP1-/- mice) display anxiety-like behavior and altered gamma-aminobutyric acid
(GABA)A-receptor pharmacology. Here, we examined associations between anxiety and
motor-function recovery in PRIP1-/- mice after a spinal cord injury (SCI) induced
by a moderate contusion injury at the 10th thoracic level. Uninjured PRIP1-/-
mice showed less distance than wild-type (WT) mice in the center 25% in an open
field test (OFT), indicating anxiety-like behavior. Anxiety behavior increased in
both WT and PRIP1-/- mice after SCI. WT and PRIP1-/- mice were completely
paralyzed on day 1 after SCI, but gradually recovered until reaching a plateau at
~4 weeks. After SCI, the PRIP1-/- mice had significantly greater motor
dysfunction than the WT mice. In WT mice after SCI, the percentage of distance
spent in the center 25% of the OFT was correlated with the OFT distance traveled
and velocity, and with the reaction time in a plantar pressure-sensitivity
mechanical test. In PRIP1-/- mice after SCI, the percentage of distance spent in
the center 25% of the OFT was correlated with the OFT distance traveled and with
the latency to fall in the rotarod test. Six weeks after SCI, ionized calcium
binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP)
expressions were elevated at the lesion epicenter in PRIP1-/- mice, and spinal
cord atrophy and demyelination were more severe than in WT mice. The axonal fiber
development was also decreased in PRIP1-/- mice, consistent with the poor motor
function recovery after SCI in these mice.
PMID- 29336202
TI - The Prediction Value of the Systemic Inflammation Score for Oral Cavity Squamous
Cell Carcinoma.
AB - Objectives This study aimed to investigate the potential prognostic role of the
oral cancer systemic inflammation score (SIS) based on serum albumin levels and
the lymphocyte-to-monocyte ratio in patients with oral squamous cell carcinoma
(OSCC) after treatment. Study Design A retrospective cohort study. Setting
Tertiary care center. Subjects and Methods The study involved 613 patients who
were treated for OSCC between September 2005 and December 2014. The association
of the oral cancer SIS with various clinicopathological features was
investigated. A nomogram based on different clinicopathological features and SIS
was established to predict prognosis. Results Higher SIS was significantly
associated with older age ( P = .0013), advanced tumor status ( P < .0001), tumor
depth ( P < .0001), advanced overall pathologic stage ( P < .0001), and
extranodal extension ( P = .0045), as well as the presence of perineural invasion
( P = .0341). Higher SIS, older age, overall stage, and extranodal extension were
demonstrated to be independent prognostic indicators for shorter overall survival
( P < .0001). A nomogram comprising SIS, TNM stage, and the degree of cell
differentiation, as well as perineural invasion and extranodal extension, was
developed to predict the prognosis of these patients. The c-index of the nomogram
model based on TNM staging only was 0.688 and could be increased to 0.752 if SIS
and several other clinicopathological parameters were incorporated. Conclusions
Higher SIS is associated with many poor prognosticators, and the nomogram that
was established and based on the incorporation of SIS might strengthen the
prediction of prognosis in patients with OSCC.
PMID- 29336203
TI - Aberrant interactions of peripheral measures and neurometabolites with lipids in
complex regional pain syndrome using magnetic resonance spectroscopy: A pilot
study.
AB - Background The aim of this study was to assess peripheral measures and central
metabolites associated with lipids using magnetic resonance spectroscopy. Results
Twelve patients with complex regional pain syndrome (CRPS) and 11 healthy
controls participated. Using magnetic resonance spectroscopy, we measured the
levels of lipid 13a (Lip13a) and lipid 09 (Lip09) relative to total creatine
(tCr) levels in the right and left thalamus. We found negative correlations of
Lip13a/tCr in the right thalamus with red blood cells or neutrophils, but a
positive correlation between Lip13a/tCr and lymphocytes in the controls. We found
negative correlations between Lip09/tCr and peripheral pH or platelets in the
controls. There were positive correlations between Lip09a/tCr and myo
inositol/tCr, between Lip13a/tCr and N-acetylaspartate (NAA)/tCr, and between
Lip09/tCr and NAA/tCr in healthy controls. On the other hand, there were positive
correlations between Lip13a/tCr and Lip09/tCr and urine pH in CRPS patients.
There were significant correlations between Lip13a/tCr or Lip09/tCr and different
peripheral measures depending on the side of the thalamus (right or left) in CRPS
patients. Conclusion This is the first report indicating that abnormal
interactions of Lip13a and Lip09 in the thalamus with peripheral measures and
central metabolites may mediate the complex pathophysiological mechanisms
underlying CRPS.
PMID- 29336205
TI - Prediction of natalizumab anti-drug antibodies persistency.
AB - BACKGROUND: Anti-drug antibodies (ADA) against natalizumab develop early during
treatment. ADA persistency is defined by two consecutive positive results as
performed by the current qualitative ELISA assay (positive/negative). Very little
is known about the magnitude of the natalizumab ADA response and persistency.
DESIGN/METHODS: We developed a highly sensitive natalizumab ADA titration assay
on the Meso Scale Discovery (MSD) platform and a pharmacokinetic (PK) assay. We
included 43 patients with a positive ELISA-ADA result within 6 months of
treatment initiation (baseline) of whom a follow-up serum sample was available 12
30 months after treatment start. MSD-ADA titres and drug levels were measured.
RESULTS: Median MSD-ADA titre at baseline was 4881 and 303 at follow-up. A titre
of >400 at baseline had a 94% sensitivity and 89% specificity to predict ADA
persistency. Reversion to ADA negativity occurred in 10 patients with mean drug
levels of 10.8 MUg/mL. The median trough drug level in ADA-positive samples was 0
ug/mL. PK levels and ADA titres correlated strongly negatively ( r = -0.67).
CONCLUSION: High baseline natalizumab ADA titres accurately predict persistency.
Despite continuous treatment, the majority of patients with persistent ADA had no
detectable drug levels indicating loss of efficacy in line with phase 3 study
results.
PMID- 29336206
TI - Working in global health: A planning and implementation framework for
international electives.
AB - PURPOSE: Propose a framework for planning and undertaking an international
elective. METHODS: On returning from conducting maternal health and well-being
research in several remote communities in India, two undergraduate medical
students have reflected on and documented their experiences with the view to
assisting other students (and their supervisors) considering undertaking an
international elective. RESULTS: A framework for undertaking clinical or research
electives in remote or rural communities is presented. The framework comprises
three distinct phases: Pre-departure planning and briefing, in-country
experiences and returning from the elective and considers a range of factors to
ensure that, as a minimum, visiting students "do no harm" and are themselves not
harmed. CONCLUSIONS: Students' home institutions have a duty of care for
preparing them for their international electives by providing pre-departure
training, support during the elective and comprehensive de-briefing on their
return. These electives should be evaluated (including by host communities) to
ensure that exchanges are socially accountable, with no harm to the often
vulnerable communities in which students gain considerable experience. Also
important is that future students build on the positive experiences of their
predecessors to ensure sustainability of any interventions in host communities.
PMID- 29336204
TI - Continuous Infusion of Phenelzine, Cyclosporine A, or Their Combination:
Evaluation of Mitochondrial Bioenergetics, Oxidative Damage, and Cytoskeletal
Degradation following Severe Controlled Cortical Impact Traumatic Brain Injury in
Rats.
AB - To date, all monotherapy clinical traumatic brain injury (TBI) trials have
failed, and there are currently no Food and Drug Administration (FDA)-approved
pharmacotherapies for the acute treatment of severe TBI. Due to the complex
secondary injury cascade following injury, there is a need to develop multi
mechanistic combinational neuroprotective approaches for the treatment of acute
TBI. As central mediators of the TBI secondary injury cascade, both mitochondria
and lipid peroxidation-derived aldehydes make promising therapeutic targets.
Cyclosporine A (CsA), an FDA-approved immunosuppressant capable of inhibiting the
mitochondrial permeability transition pore, and phenelzine (PZ), an FDA-approved
monoamine oxidase inhibitor capable of scavenging neurotoxic lipid peroxidation
derived aldehydes, have both been shown to be partially neuroprotective following
experimental TBI. Therefore, it follows that the combination of PZ and CsA may
enhance neuroprotection over either agent alone through the combining of distinct
but complementary mechanisms of action. Additionally, as the first 72 h
represents a critical time period following injury, it follows that continuous
drug infusion over the first 72 h following injury may also lead to optimal
neuroprotective effects. This is the first study to examine the effects of a 72 h
subcutaneous continuous infusion of PZ, CsA, and the combination of these two
agents on mitochondrial respiration, mitochondrial bound 4-hydroxynonenal (4
HNE), and acrolein, and alpha-spectrin degradation 72 h following a severe
controlled cortical impact injury in rats. Our results indicate that
individually, both CsA and PZ are able to attenuate mitochondrial 4-HNE and
acrolein, PZ is able to maintain mitochondrial respiratory control ratio and
cytoskeletal integrity but together, PZ and CsA are unable to maintain
neuroprotective effects.
PMID- 29336207
TI - Cytotoxicity of Ciprofloxacin and Steroids in Mouse Tympanic Membrane
Fibroblasts.
AB - Objective Ciprofloxacin, commonly given as eardrops, has been shown to adversely
affect tympanic membrane fibroblasts. Dexamethasone potentiates this effect. A
newly available eardrop contains ciprofloxacin and fluocinolone, a more potent
steroid. We evaluated the cytotoxic effects of this preparation on mouse tympanic
membrane fibroblasts. Study Design Prospective, in vitro. Setting Academic
laboratory. Subjects and Methods In experiment 1, fibroblasts were exposed to
1:10 dilutions of commercially available 0.3% ofloxacin, 0.3% ciprofloxacin, 0.3%
ciprofloxacin + 0.1% dexamethasone, 0.3% ciprofloxacin + 0.025% fluocinolone, or
dilute hydrochloric acid (control), twice within 24 hours. In experiment 2, cells
were also treated with the dilutions of the pure form of dexamethasone 0.1% or
fluocinolone 0.025%, alone and in combination with ofloxacin or ciprofloxacin.
Cells were exposed to the solutions for 2 hours each time and were placed back in
growth media after the treatments. Cells were observed with phase-contrast
microscope until the cytotoxicity assay was performed. Results Survival of
fibroblasts treated with ofloxacin was not different from the control.
Fibroblasts treated with ciprofloxacin, ciprofloxacin + dexamethasone, or
ciprofloxacin + fluocinolone had much lower survival (all P < .0001). Cells
treated with ciprofloxacin + fluocinolone had lower survival than ciprofloxacin (
P < .0001) and ciprofloxacin + dexamethasone ( P = .0001). Steroids alone also
decreased fibroblast survival compared to control ( P < .0001). The combination
of dexamethasone or fluocinolone with ciprofloxacin, but not ofloxacin, further
decreased fibroblast survival ( P < .0001). Phase-contrast images mirrored the
cytotoxicity findings. Conclusion Tympanic membrane fibroblast cytotoxicity of
ciprofloxacin is potentiated by corticosteroids. This effect may be deleterious
when treating a healing perforation but beneficial when treating granulation
tissue on the tympanic membrane.
PMID- 29336208
TI - The Effects of Sex Differences and Hormonal Contraception on Outcomes after
Collegiate Sports-Related Concussion.
AB - There is conflicting evidence regarding whether females are more adversely
affected after concussion than males. Further, recent research suggests that
hormonal contraceptive (HC) use may affect symptom severity and duration post
concussion. The objective of this study was to examine the effects of sex and HC
use on outcomes following concussion among collegiate varsity athletes. We
hypothesized that females would have longer length of recovery (LOR), and that
peak symptom severity would be associated with longer LOR in both males and
females. Among females, we hypothesized that non-HC users would have longer LOR
and higher peak symptom severity than HC users. Ninety collegiate student
athletes were included in this study (40 males, 50 females; 24 HC users, 25 non
HC users). Demographic, injury, and recovery information was abstracted via
retrospective record review. LOR was defined as days between injury and clearance
for full return to play by team physician. Peak symptom severity score (Sport
Concussion Assessment Tool [SCAT] 2 or 3) was used in analyses. Study results
revealed that males had shorter LOR than females (F[1, 86] = 5.021, p < 0.05, d =
0.49), but had comparable symptom severity scores. Symptom severity was strongly
related to LOR for males (r = 0.513, p < 0.01) but not females (r = -0.003, p >
0.05). Among females, non-HC users demonstrated higher symptom severity than HC
users (F[1,47] = 5.142, p < 0.05, d = 0.70). No significant differences between
female HC users and non-HC users on LOR were observed. This study provides
evidence for differential concussion outcomes between male and female collegiate
athletes and between HC users and nonusers among females.
PMID- 29336209
TI - Effects of Treadmill Training Combined with Serotonergic Interventions on
Spasticity after Contusive Spinal Cord Injury.
AB - Spasticity usually emerges during the course of recovery from spinal cord injury
(SCI). While medications and physical rehabilitation are prescribed to alleviate
spastic symptoms, the insufficiency of their effects remains an important problem
to be addressed. Given the challenges associated with increasing the dose of
medication, we hypothesized that a combination therapy with medication and
physical rehabilitation can be effective. Therefore, we examined the effects of
treadmill training (TMT) along with serotonergic medication using a spastic rat
model after contusive injury. Spasticity-strong SCI rats were selected 4 weeks
after SCI and received one of the following interventions for 2 weeks: only TMT,
TMT with fluoxetine (a selective serotonin re-uptake inhibitor), TMT with
cyproheptadine (a 5-HT2 receptor antagonist), only fluoxetine, or only
cyproheptadine. We performed the swimming test to quantify the frequency of
spastic behaviors. We also evaluated hindlimb locomotor functions every week. At
the end of the intervention, we examined the Hoffman reflex from the plantar
muscle and the immunoreactivity of the 5-HT2A receptor in spinal cord tissues.
While the TMT group and cyproheptadine-treated groups showed decreased spastic
behaviors and reduction in spinal hyperreflexia, the fluoxetine-treated group
showed the opposite effect, even with TMT. Moreover, TMT suppressed the
expression of the 5-HT2A receptor in the lumbar spinal motor neurons, while
cyproheptadine treatment did not change it. We did not observe any differences in
locomotor functions between the groups. Taken together, our findings indicate
that TMT and cyproheptadine significantly alleviated spastic symptoms, but did
not show synergistic or additive effects.
PMID- 29336210
TI - Semi-supervised identification of cancer subgroups using survival outcomes and
overlapping grouping information.
AB - Identification of cancer patient subgroups using high throughput genomic data is
of critical importance to clinicians and scientists because it can offer
opportunities for more personalized treatment and overlapping treatments of
cancers. In spite of tremendous efforts, this problem still remains challenging
because of low reproducibility and instability of identified cancer subgroups and
molecular features. In order to address this challenge, we developed Integrative
Genomics Robust iDentification of cancer subgroups (InGRiD), a statistical
approach that integrates information from biological pathway databases with high
throughput genomic data to improve the robustness for identification and
interpretation of molecularly-defined subgroups of cancer patients. We applied
InGRiD to the gene expression data of high-grade serous ovarian cancer from The
Cancer Genome Atlas and the Australian Ovarian Cancer Study. The results indicate
clear benefits of the pathway-level approaches over the gene-level approaches. In
addition, using the proposed InGRiD framework, we also investigate and address
the issue of gene sharing among pathways, which often occurs in practice, to
further facilitate biological interpretation of key molecular features associated
with cancer progression. The R package "InGRiD" implementing the proposed
approach is currently available in our research group GitHub webpage (
https://dongjunchung.github.io/INGRID/ ).
PMID- 29336211
TI - The effect of altering loading distance on skeleton start performance: Is higher
pre-load velocity always beneficial?
AB - Athletes initiating skeleton runs differ in the number of steps taken before
loading the sled. We aimed to understand how experimentally modifying loading
distance influenced sled velocity and overall start performance. Ten athletes
(five elite, five talent; 67% of all national athletes) underwent two to four
sessions, consisting of two dry-land push-starts in each of three conditions
(preferred, long and short loading distances). A magnet encoder on the sled wheel
provided velocity profiles and the overall performance measure (sled acceleration
index). Longer pre-load distances (12% average increase from preferred to long
distances) were related to higher pre-load velocity (r = 0.94), but lower load
effectiveness (r = -0.75; average reduction 29%). Performance evaluations across
conditions revealed that elite athletes' preferred distance push-starts were
typically superior to the other conditions. Short loading distances were
generally detrimental, whereas pushing the sled further improved some talent
squad athletes' performance. Thus, an important trade-off between generating high
pre-load velocity and loading effectively was revealed, which coaches should
consider when encouraging athletes to load later. This novel intervention study
conducted within a real-world training setting has demonstrated the scope to
enhance push-start performance by altering loading distance, particularly in
developing athletes with less extensive training experience.
PMID- 29336212
TI - Simulated Microgravity Impairs Cardiac Autonomic Neurogenesis from Neural Crest
Cells.
AB - Microgravity-induced alterations in the autonomic nervous system (ANS) contribute
to derangements in both the mechanical and electrophysiological function of the
cardiovascular system, leading to severe symptoms in humans following space
travel. Because the ANS forms embryonically from neural crest (NC) progenitors,
we hypothesized that microgravity can impair NC-derived cardiac structures.
Accordingly, we conducted in vitro simulated microgravity experiments employing
NC genetic lineage tracing in mice with cKitCreERT2/+, Isl1nLacZ, and Wnt1-Cre
reporter alleles. Inducible fate mapping in adult mouse hearts and pluripotent
stem cells (iPSCs) demonstrated reduced cKitCreERT2/+-mediated labeling of both
NC-derived cardiomyocytes and autonomic neurons (P < 0.0005 vs. controls). Whole
transcriptome analysis, suggested that this effect was associated with repressed
cardiac NC- and upregulated mesoderm-related gene expression profiles, coupled
with abnormal bone morphogenetic protein (BMP)/transforming growth factor beta
(TGF-beta) and Wnt/beta-catenin signaling. To separate the manifestations of
simulated microgravity on NC versus mesodermal-cardiac derivatives, we conducted
Isl1nLacZ lineage analyses, which indicated an approximately 3-fold expansion (P
< 0.05) in mesoderm-derived Isl-1+ pacemaker sinoatrial nodal cells; and an
approximately 3-fold reduction (P < 0.05) in cardiac NC-derived ANS cells,
including sympathetic nerves and Isl-1+ cardiac ganglia. Finally, NC-specific
fate mapping with a Wnt1-Cre reporter iPSC model of murine NC development
confirmed that simulated microgravity directly impacted the in vitro development
of cardiac NC progenitors and their contribution to the sympathetic and
parasympathetic innervation of the iPSC-derived myocardium. Altogether, these
findings reveal an important role for gravity in the development of NCs and their
postnatal derivatives, and have important therapeutic implications for human
space exploration, providing insights into cellular and molecular mechanisms of
microgravity-induced cardiomyopathies/channelopathies.
PMID- 29336213
TI - Heart versus head: Differential bodily feedback causally alters economic decision
making.
AB - Metaphorically, altruistic acts, such as monetary donations, are said to be
driven by the heart, whereas sound financial investments are guided by reason,
embodied by the head. In a unique experiment, we tested the effects of these
bodily metaphors using biofeedback and an incentivized economic decision-making
paradigm. Participants played a repeated investment game with a simulated
partner, alternating between tactical investor and altruistic investee. When
making decisions, participants received counterbalanced visual feedback from
their own or a simulated partner's heart or head, as well as no feedback. As
investor, participants transferred a greater proportion of their endowments when
exposed to visual feedback from their own head than to feedback from their own
heart or no feedback at all. These effects were not observed when the source of
the feedback was the simulated partner. As investee, heart feedback predicted
greater altruistic returns than head or no feedback, but this effect did not
differ based on source (own vs partner). Consistent with a dual-process
framework, we suggest that people may be encouraged to invest more or be more
altruistic when receiving bodily feedback from conceptually diametric sources.
PMID- 29336214
TI - Direct red 81 adsorption on iron filings from aqueous solutions; kinetic and
isotherm studies.
AB - Direct Red 81 (DR-81) dye with a very high water solubility is widely used in
many industries particularly textile industries. This study aimed to evaluate the
practicability of using iron filings for the adsorption of DR-81 dye from the
aqueous solutions. The effects of pH, adsorbent dose, initial DR-81 dye
concentration, and adsorption time on adsorption process were also evaluated. The
maximum of adsorption efficiency of DR-81 dye achieved in the optimum pH: 3,
adsorbent dose: 2.5 g/L, contact time: 30 min, and initial dye concentration: 50
mg/L. The dye adsorption efficiency is increased by increasing the adsorbent dose
and adsorption time. The kinetic and isotherm studies indicated that the
adsorption process obeys a pseudo-first-order and Langmuir isotherm models. The
experimental studies indicated that iron filings had the potential to act as an
alternative adsorbent to remove the DR-81 dye from an aqueous solution.
PMID- 29336215
TI - Noninvasive Real-Time Assessment of Cell Viability in a Three-Dimensional Tissue.
AB - Maintaining cell viability within 3D tissue engineering scaffolds is an essential
step toward a functional tissue or organ. Assessment of cell viability in 3D
scaffolds is necessary to control and optimize tissue culture process. Monitoring
systems based on respiration activity of cells (e.g., oxygen consumption) have
been used in various cell cultures. In this research, an online monitoring system
based on respiration activity was developed to monitor cell viability within
acellular lung scaffolds. First, acellular lung scaffolds were recellularized
with human umbilical cord vein endothelial cells, and then, cell viability was
monitored during a 5-day period. The real-time monitoring system generated a cell
growth profile representing invaluable information on cell viability and
proliferative states during the culture period. The cell growth profile obtained
by the monitoring system was consistent with 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide analysis and glucose consumption measurement. This
system provided a means for noninvasive, real-time, and repetitive investigation
of cell viability. Also, we showed the applicability of this monitoring system by
introducing shaking as an operating parameter in a long-term culture.
PMID- 29336216
TI - Sulfamethoxazole removal in membrane-photocatalytic reactor system -
experimentation and modelling.
AB - In this study, the efficacy of membrane-photocatalytic reactor (MPR) in
sulfamethoxazole (SMX) removal was explored at a fixed initial SMX concentration,
i.e. 100 mg/L. A supported catalyst, i.e. TiO2 on granular activated carbon (GAC
TiO2), was used for MPR experiments. The SMX removal efficiency of the MPR was
investigated under a range of hydraulic retention time (i.e. HRT from 51 to 152.5
min) and TiO2 catalyst dosage (55-50 mg/L). A maximum SMX removal efficiency of
83.6% was observed under 220 mg/L catalyst dosage and 80 min HRT. The increase in
catalyst dosage from 55 to 550 mg/L has increased the transmembrane pressure of
the reactor from 9.8 to 22.2 kPa. A multiple non-linear regression model was
developed based on the experimental data and its significance was analyzed using
two-way ANOVA. Based on the model, the optimal HRT and catalyst dosage for
complete SMX removal (100%) were found out. The comparison of photocatalytic
degradation experiments with sorption experiments conducted earlier revealed that
SMX removal in the MPR was mainly by photocatalytic degradation and not by
adsorption onto GAC-TiO2 catalyst. However, the performance of MPR in removing
other emerging pollutants from real-time wastewaters could be explored before its
field-scale application.
PMID- 29336217
TI - Coronary anomaly: when you think you've seen it all.
PMID- 29336218
TI - The different audiences of science communication: A segmentation analysis of the
Swiss population's perceptions of science and their information and media use
patterns.
AB - Few studies have assessed whether populations can be divided into segments with
different perceptions of science. We provide such an analysis and assess whether
these segments exhibit specific patterns of media and information use. Based on
representative survey data from Switzerland, we use latent class analysis to
reconstruct four segments: the "Sciencephiles," with strong interest for science,
extensive knowledge, and a pronounced belief in its potential, who use a variety
of sources intensively; the "Critically Interested," also with strong interest
and support for science but with less trust in it, who use similar sources but
are more cautious toward them; the "Passive Supporters" with moderate levels of
interest, trust, and knowledge and tempered perceptions of science, who use fewer
sources; and the "Disengaged," who are not interested in science, do not know
much about it, harbor critical views toward it, and encounter it-if at all-mostly
through television.
PMID- 29336219
TI - Asymmetricity Between Sister Cells of Pluripotent Stem Cells at the Onset of
Differentiation.
AB - Various somatic stem cells divide asymmetrically; however, it is not known
whether embryonic stem cells (ESCs) divide symmetrically or asymmetrically, not
only while maintaining an undifferentiated state but also at the onset of
differentiation. In this study, we observed single ESCs using time-lapse imaging
and compared sister cell pairs derived from the same mother cell in either the
maintenance or differentiation medium. Mouse ESCs were cultured on E-cadherin
coated glass-based dishes, which allowed us to trace single cells. The
undifferentiated cell state was detected by green fluorescent protein (GFP)
expression driven by the Nanog promoter, which is active only in undifferentiated
cells. Cell population analysis using flow cytometry showed that the peak width
indicating distribution of GFP expression broadened when cells were transferred
to the differentiation medium compared to when they were in the maintenance
medium. This finding suggested that the population of ESCs became more
heterogeneous at the onset of differentiation. Using single-cell analysis by time
lapse imaging, we found that although the total survival ratio decreased by
changing to differentiation medium, the one-live-one-dead ratio of sister cell
pairs was smaller compared with randomly chosen non-sister cell pairs, defined as
an unsynchronized cell pair control, in both media. This result suggested that
sister cell pairs were more positively synchronized with each other compared to
non-sister cell pairs. The differences in interdivision time (the time interval
between mother cell division and the subsequent cell division) between sister
cells was smaller than that between non-sister cell pairs in both media,
suggesting that sister cells divided synchronously. Although the difference in
Nanog-GFP intensity between sister cells was smaller than that between non-sister
cells in the maintenance medium, it was the same in differentiation medium,
suggesting asymmetrical Nanog-GFP intensity. These data suggested that ESCs may
divide asymmetrically at the onset of differentiation resulting in heterogeneity.
PMID- 29336220
TI - High Serum Cholesterol Is a Novel Risk Factor for Graves' Orbitopathy: Results of
a Cross-Sectional Study.
AB - BACKGROUND: Limited data suggest that treatment with statins is associated with a
reduced risk of Graves' orbitopathy (GO) in patients with Graves' disease (GD),
attributed to the anti-inflammatory rather than to the hypolipemic effects of
these medications. The aim of the present study was to investigate whether there
is an association between high cholesterol and GO. The primary outcome was the
relation between GO and low-density lipoprotein (LDL)-cholesterol. The secondary
outcomes were the relation between severity or activity (the clinical activity
score [CAS]) of GO and LDL-cholesterol. METHODS: A cross-sectional investigation
was conducted in consecutive patients with GD who came under the authors'
observation to undergo radioiodine treatment, a stratification aimed at forming
two distinct groups of patients under the same conditions. A total of 250
patients were enrolled, 133 with and 117 without GO. Ophthalmological assessments
and serum lipids measurements were performed. RESULTS: In multivariate analyses
with correction for the duration of hyperthyroidism, a variable that differed
between patients with respect to the presence or absence of GO, a correlation
between the presence of GO and both total (p = 0.01) and LDL-cholesterol (p =
0.02) was observed. In patients with hyperthyroidism lasting <44 months, total
and LDL-cholesterol were higher (p = 0.01 and p = 0.008, respectively) among GO
patients. In this subgroup, based on the presence/absence of GO, cutoff values
were established for total (191 mg/dL) and LDL-cholesterol (118.4 mg/dL), above
which an increased risk of GO was observed (total cholesterol relative risk:
1.47; p = 0.03; LDL-cholesterol relative risk: 1.28; p = 0.03). GO severity and
CAS did not correlate with serum lipids. However, CAS was found to be higher (p =
0.02) in patients with high total cholesterol. When the analysis was restricted
to untreated GO patients, a correlation was found between CAS and both total (p =
0.04) and LDL-cholesterol (p = 0.03), after adjustment for GO duration.
CONCLUSIONS: In patients with a short duration of hyperthyroidism, total and LDL
cholesterol correlate with the presence of GO, suggesting a role of cholesterol
in the development of GO. Depending on GO duration, total and LDL-cholesterol
correlate with GO activity, suggesting a role of cholesterol in the clinical
expression of GO.
PMID- 29336221
TI - Sequelae of Tympanostomy Tubes in a Multihospital Health System.
AB - Objectives Review the incidence of long-term sequelae after placement of
tympanostomy tubes. Study Design Case series with chart review. Setting
Multihospital network. Subjects Patients 0 to 3 years old undergoing tympanostomy
tube (TT) placement. Methods A case series of 14,058 children between 2004 and
2010 was reviewed. The patients were followed for 5 years to determine number of
repeated tube placements, need for surgical removal of tubes, and presence of
perforation requiring repair. Results The study cohort included 14,058 children
who underwent TT placement. The mean age at time of procedure was 1.4 years. A
total of 14.4% of patients required a second set of tubes within the 5 years of
follow-up studied, and 4.6% required 3 or more sets. Three percent required
removal of a tube, and this occurred at an average time of 34.2 +/- 17.6 months
postplacement. In total, 5.1% had a resulting perforation after either tube
extrusion or tube removal requiring myringoplasty. Conclusions The rate of
multiple tube placements and myringoplasty and tympanoplasty to correct resulting
perforations has yet to be studied in a single large population. This information
allows for more detailed preoperative counseling to patients and families. Better
characterization of these populations with accurate rates of sequelae can help to
tailor treatment and preoperative counseling in the future.
PMID- 29336222
TI - Implementing a Health Home: Michigan's Experience.
AB - As the number of individuals in the United States with chronic conditions and the
associated costs in caring for these individuals continues to rise, there is a
need to transform how health care services are delivered. Under Section 2703 of
the Affordable Care Act of 2010, the federal government provides state Medicaid
programs the opportunity to improve care coordination for people with chronic
conditions in a person-centered approach through the establishment of health
homes. Given the complexity of care for Medicaid beneficiaries with chronic
conditions, addressing the social determinants of health and providing integrated
care are central to effectively improving health outcomes and generating cost
savings. Although launching a health home model is a step toward improving care
coordination and care management for high-risk individuals, there are myriad
components to implementing such a program. The purpose of this article is to
explain the process that Michigan policymakers undertook to implement its Section
2703 Medicaid health home initiative, named the MI Care Team. The authors present
lessons learned for policymakers and stakeholders in other states seeking to
implement a Medicaid health home and explain how the nursing profession is
integral for health homes.
PMID- 29336223
TI - Assessment of safety culture among job positions in high-rise construction: a
hybrid fuzzy multi criteria decision-making (FMCDM) approach.
AB - The construction industry is known as one of the most dangerous industries, which
not only requires sound operation of executive laws and regulations, but also
necessitates the safety culture of all workers at workshops. Therefore, the aim
of this research is to identify the factors of safety culture and ranking
occupations in jobsites based on those factors in order to proactively improve
the safety culture of construction projects and subsequently promote safety
conditions and worksites. In this study, safety culture criteria are weighted by
a combination of Fuzzy Decision Trail and Evaluation Laboratory and Fuzzy ANP
methods. Next, different job positions in high-rise projects are ranked using the
Fuzzy Technique for Order of Preference by Similarity to Ideal Solution method.
Findings demonstrated that the project manager, site superintendent and
supervisor occupations had the highest and labourers had the lowest level of
safety culture in the high-rise construction industry. Furthermore, factors such
as safety supervision and training must be considered more seriously in order to
create a positive safety culture among workers.
PMID- 29336224
TI - Treatment of a Klebsiella pneumoniae KPC cellulitis and gut decolonization with
ceftazidime/avibactam in a migrant from Libya.
AB - KPC-producing Klebsiella pneumoniae (KPC-Kp) is nowadays a global concern.
Ceftazidime/avibactam is the most promising novel antibiotic combination
available at the moment. We describe the case of a migrant with no risk factors
for an infection due to multidrug resistant bacteria. He suffered from a KPC-Kp
cellulitis and was treated with a ceftazidime/avibactam-meropenem-fosfomycin
combination that not only eradicated the infection but also decontaminated his
gut. Ceftazidime/avibactam-based treatment can be useful also in decontamination
procedures.
PMID- 29336225
TI - A robust likelihood approach to inference about the kappa coefficient for
correlated binary data.
AB - We construct a legitimate likelihood function for the agreement kappa coefficient
for correlated data without specifically modelling all levels of correlation.
This makes available the likelihood ratio test, the score test and other tools
without the knowledge of the underlying distributions. This parametric robust
likelihood approach applies to general clustered data scenarios. We provide
simulations and real data analysis to demonstrate the advantage of the robust
procedure.
PMID- 29336226
TI - Identifying Metrics before and after Readmission following Head and Neck Surgery
and Factors Affecting Readmission Rate.
AB - Objectives Determine nationally representative readmission rates after head and
neck cancer (HNCA) surgery and factors associated with readmission. Study Design
Cross-sectional analysis of admissions database. Methods The 2013 Nationwide
Readmissions Database was analyzed for HNCA surgery admissions and subsequent
readmission within 30 days. The readmission rate, length of stay (LOS),
disposition, mortality rate, and total charges were determined. Diagnoses and
procedures upon readmission were quantified. Factors that were associated with
readmission were determined. Results In total, 132,755 HNCA surgery inpatient
admissions (mean age, 57.3 years; 52.2% male) were analyzed. Nationally
representative metrics for HNCA surgery were mean LOS (4.4 +/- 0.1 days),
disposition (home without services, 80.5%; home health care, 10.9%; and skilled
facility, 6.6%), mortality rate (1.0% +/- 0.1%), and total charges ($53,106 +/-
$1167). The readmission rate was 7.7% +/- 0.2% (mean readmission postoperative
days, 17.1 +/- 0.1), with readmission LOS (5.6 +/- 0.1 days), mortality rate
(3.7% +/- 0.3%), and total charges ($49,425 +/- $1548). The most common diagnoses
at readmission included surgical complications (15.5%), mental health and
substance abuse (13.1%), hypertension (12.8%), septicemia/infection (12.1%),
gastrointestinal disease (11.3%), nutritional/metabolic disorders (10.1%),
electrolyte abnormalities (8.5%), and esophageal disorders (8.1%). In
multivariate analyses, male sex, increasing All Patients Refined Diagnosis
Related Group (APR-DRG) severity score, and initial LOS were associated with
readmission (odds ratio [95% confidence interval], 1.11 [1.04-1.20], 1.94 [1.77
2.12], and 1.34 [1.22-1.48], respectively), whereas age and discharge location
were not ( P = .361 and .482). Conclusion HNCA surgery readmission is associated
with significant increases in services/skilled care on discharge, mortality, and
additional total health care cost. This national analysis identifies common
readmission diagnoses to target to prevent readmissions.
PMID- 29336227
TI - Extracts from Lupinus albescens: antioxidant power and antifungal activity in
vitro against phytopathogenic fungi.
AB - Fungi are considered the most damaging microorganisms in agriculture. The
indiscriminate use of chemical treatments in agricultural products causes the
development of pest resistance and affects human health. An alternative to
synthetic fungicides is the use of natural products such as plant extracts for
the management of fungal diseases in plants. Extracts from different parts of
Lupinus albescens (roots, stalks, leaves, and flowers) were obtained by
extraction using supercritical carbon dioxide (CO2) or compressed liquefied
petroleum gas (LPG). Thereafter, the antioxidant activity of each extract was
measured, and the antifungal activity in vitro of extracts was evaluated against
Fusarium oxysporum and Fusarium verticillioides. For a concentration of 5000
mg/L, the half maximal inhibitory concentration (IC50) ranged from 29.25 MUg/mL
to 192.96 MUg/mL. Antifungal tests showed that all matrices presented inhibitory
effect against both fungi tested. The extracts obtained from roots by CO2 and LPG
presented 70.1% and 65.1% inhibition against F. oxysporum, and 67.8% and 61.2%
inhibition against F. verticillioides, respectively. These results suggest that
the extracts obtained from L. albescens by extractions using supercritical CO2
and compressed LPG might be a potential source of antioxidants and natural
fungicides.
PMID- 29336228
TI - The Multitheoretical List of Therapeutic Interventions - 30 items (MULTI-30).
AB - OBJECTIVE: To develop a brief version of the Multitheoretical List of Therapeutic
Interventions (MULTI-60) in order to decrease completion time burden by
approximately half, while maintaining content coverage. Study 1 aimed to select
30 items. Study 2 aimed to examine the reliability and internal consistency of
the MULTI-30. Study 3 aimed to validate the MULTI-30 and ensure content coverage.
METHOD: In Study 1, the sample included 186 therapist and 255 patient MULTI
ratings, and 164 ratings of sessions coded by trained observers. Internal
consistency (Chronbach's alpha and McDonald's omega) was calculated and
confirmatory factor analysis was conducted. Psychotherapy experts rated content
relevance. Study 2 included a sample of 644 patient and 522 therapist ratings,
and 793 codings of psychotherapy sessions. In Study 3, the sample included 33
codings of sessions. A series of regression analyses was conducted to examine
replication of previously published findings using the MULTI-30. RESULTS: The
MULTI-30 was found valid, reliable, and internally consistent across 2564 ratings
examined across the three studies presented. CONCLUSION: The MULTI-30 a brief and
reliable process measure. Future studies are required for further validation.
PMID- 29336229
TI - Parasites of importance for human health on edible fruits and vegetables in
Nigeria: a systematic review and meta-analysis of published data.
AB - Contamination of edible fruits and vegetables is now a global public health issue
despite their health benefits as non-pharmacological prophylaxis against chronic
diseases. Studies that will harness the extent of parasitic contaminations will
ensure public health protection. Here, the prevalence and distribution of
parasites of importance for human health on fruits and vegetables in Nigeria were
determined through a systematic review and meta-analysis of published data. The
random-effects model was used to determine pooled prevalence estimate (PPE).
Heterogeneity was evaluated by the Cochran's Q-test. Parasites overall PPE of
32.4% (95% CI: 0.73, 0.91) was observed from 19 eligible studies reported across
13 Nigerian states. Sub-groups PPEs ranged between 3.5% (95% CI: 0.45, 1.86) and
58.5% (95% CI: 1.40, 4.09). A high degree of heterogeneity 97.53% (95% CI: 0.30,
0.46, P: 0.000) was observed within studies and sub-groups. Cryptosporidium
species were the most prevalent, while Ancylostoma duodenale and Ascaris
lumbricoides had the widest geographical distribution. Pineapple (Prev: 41.3%,
95% CI: 0.40, 0.75) and lettuce (Prev: 51.5%, 95% CI: 0.37, 0.68) recorded the
highest level of parasitic contamination. Parasites of importance for human
health are prevalent on edible fruits and vegetables in Nigeria. Prevalence
estimates were highest in the South-eastern region and during the most recent
decade. Adequate washing of fruits and vegetables, on-farm irrigation of
vegetables using good sources of water and adequate hygiene by food handlers will
help the general public to maximize the health benefits associated with the
intake of fruits and vegetables while minimizing the risk of acquiring parasitic
infections.
PMID- 29336230
TI - Alterations of Global DNA Methylation and DNA Methyltransferase Expression in T
and B Lymphocytes from Patients with Newly Diagnosed Autoimmune Thyroid Diseases
After Treatment: A Follow-Up Study.
AB - BACKGROUND: Dysregulated DNA methylation in lymphocytes has been linked to
autoimmune disorders. The aims of this study were to identify global DNA
methylation patterns in patients with autoimmune thyroid diseases and to observe
methylation changes after treatment for these conditions. METHODS: A cross
sectional study was conducted, including the following patients: 51 with newly
diagnosed Graves' disease (GD), 28 with autoimmune hypothyroidism (AIT), 29 with
positive thyroid autoantibodies, and 39 matched healthy volunteers. Forty GD
patients treated with radioiodine or antithyroid drugs and 28 AIT patients
treated with L-thyroxine were followed for three months. Serum free
triiodothyronine, free thyroxine, thyrotropin, thyroid peroxidase antibodies,
thyroglobulin antibodies, and thyrotropin receptor antibodies were assayed using
electrochemiluminescent immunoassays. CD3+ T and CD19+ B cells were separated by
flow cytometry for total DNA and RNA extraction. Global DNA methylation levels
were determined by absorptiometry using a methylation quantification kit. DNA
methyltransferase (DNMT) expression levels were detected by real-time polymerase
chain reaction. RESULTS: Hypomethylation and down-regulated DNMT1 expression in T
and B lymphocytes were observed in the newly diagnosed GD patients. Neither the
AIT patients nor the positive thyroid autoantibodies patients exhibited
differences in their global DNA methylation status or DNMT mRNA levels compared
with healthy controls. Antithyroid drugs restored global methylation and DNMT1
expression in both T and B lymphocytes, whereas radioiodine therapy affected only
T cells. L-thyroxine replacement did not alter the methylation or DNMT expression
levels in lymphocytes. The global methylation levels of B cells were negatively
correlated with the serum thyroid peroxidase antibodies in patients with
autoimmune thyroid diseases. CONCLUSIONS: Hyperthyroid patients with newly
diagnosed GD had global hypomethylation and lower DNMT1 expression in T and B
lymphocytes. The results provide the first demonstration that antithyroid drugs
or radioiodine treatment restore global DNA methylation and DNMT1 expression with
concurrent relief of hyperthyroidism.
PMID- 29336232
TI - Wealth, Social Protection Programs, and Child Labor in Colombia: A Cross
sectional Study.
AB - This article has 3 main objectives: (1) to assess the prevalence of child labor
in Colombia, (2) to identify factors associated with child labor, and (3) to
determine whether social protection programs have an association with the
prevalence of child labor in the country. Using a cross-sectional study with data
from the Colombian Demographic and Health Survey 2010, a working child was
defined as a child who worked during the week prior to the survey in an activity
other than household chores. Through descriptive statistics, bivariate analysis,
and multivariate regressions, it was found that child labor was associated with
gender (boys were more likely to work), older age, ethnicity (children from
indigenous communities were more likely to be workers), school dropout,
disability (children with disabilities were less likely to be working),
subsidized health social security system membership, and lower number of years of
mother's schooling. Furthermore, the results of this study suggest that children
beneficiaries of the subsidy Familias en Accion were less likely to be working
and that social protection programs were more effective to reduce child labor
when targeting the lowest wealth quintiles of the Colombian population.
PMID- 29336231
TI - A Universal Classification System of Skin Substitutes Inspired by Factorial
Design.
AB - The complexity of the dermal layer of skin means that damage to this section can
result in permanent impairment of function. Partial or total dermal loss is a
feature of deep burns and chronic wounds such as pressure sores or diabetic
ulcers. The issues posed by traditional skin grafts have led to substantial
research being carried out in the fields of tissue engineering and biomaterials
science to develop a vast array of alternative skin substitutes. Given the large
number of different materials, manufacturing methods, and techniques for
implementation described for artificial skin substitutes, many classification
systems have been created to simplify their categorization. Some of these systems
are oriented toward clinicians while others toward researchers. However, none
address the needs of both groups and none are intuitive. The creation of an
effective classification system would be particularly helpful in the regulation,
distribution, organization, and selection of skin substitutes. The aim of this
review is to examine existing methods of classification of skin substitutes, and
to propose a new system that uses an algorithm that is inspired by factorial
design. Our system allows multiple factors to be simultaneously investigated or
in this case, described, since all skin substitutes possess multiple
characteristics: (1) cellularity (acellular or cellular), (2) layering (single
layer or bilayer), (3) replaced region (epidermis, dermis, or both), (4)
materials used (natural, synthetic, or both), and (5) permanence (temporary or
permanent). The factors and levels are combined into an algorithm where all the
possible combinations are shown. The multifactorial and palindromic structure of
our system should enable all users to quickly understand the makeup of a selected
skin substitute, or search for a skin substitute depending on their specific
requirements. We feel that our proposed classification can be used by clinicians
and biomedical researchers alike, which should be an advantage given the
multidisciplinary nature of the tissue engineering field and the science that
underpins the development of skin substitutes. We also touch upon some of the
state-of-the-art skin substitutes that are commercially available or under
development to demonstrate how our new method of classification might work.
PMID- 29336234
TI - Haemostaseological complication management in caval and iliac venous stenting.
AB - Antiplatelet and anticoagulation therapy after venous stenting is still not
standardized, data from randomized-controlled trials are missing. Rare
prothrombotic disorders and nonresponsiveness to drugs must be taken into
account. This case report demonstrates successful haemostaselogical complication
management in recurrent rethromboses due to underlying clopidogrel resistance and
low responsiveness to anticoagulation with dabigatran after endovascular stent
reconstruction of chronic pelvic and caval vein occlusion in a patient with
severe postthrombotic syndrome.
PMID- 29336235
TI - Rapid Remission of Graves' Hyperthyroidism Without Thionamides Under
Immunosuppressive Treatment for Concomitant Autoimmune Hepatitis.
PMID- 29336237
TI - Masticatory function and oral stereognosis in bruxers.
AB - OBJECTIVE: To compare the mastication and oral sensory function of individuals
with and without sleep bruxism. METHODS: The sample comprised 60 volunteers, of
which 30 were bruxers (mean age = 30.5 +/- 6.0) and 30 non-bruxers (mean age =
28.6 +/- 3.3). Sleep bruxism was clinically diagnosed and confirmed using the
Bruxoff(r) device. Mastication was evaluated according to swallowing threshold
and masticatory efficiency. Swallowing threshold was determined from the median
particle size of Optosil(r), obtained after an individualized number of
masticatory cycles, which was first determined by chewing peanuts; masticatory
efficiency was estimated by the sieving method. Oral stereognosis test was used
to determine the oral sensory function. Variables were compared using one-way
ANOVA (p < .05). RESULTS: The median particle size, masticatory efficiency, and
oral sensory function did not differ significantly between bruxers and non
bruxers (p > .05). CONCLUSION: Dentate adults present similar mastication and
oral sensory function, despite the presence of sleep bruxism.
PMID- 29336236
TI - Implementation of genomics research in Africa: challenges and recommendations.
AB - BACKGROUND: There is exponential growth in the interest and implementation of
genomics research in Africa. This growth has been facilitated by the Human
Hereditary and Health in Africa (H3Africa) initiative, which aims to promote a
contemporary research approach to the study of genomics and environmental
determinants of common diseases in African populations. OBJECTIVE: The purpose of
this article is to describe important challenges affecting genomics research
implementation in Africa. METHODS: The observations, challenges and
recommendations presented in this article were obtained through discussions by
African scientists at teleconferences and face-to-face meetings, seminars at
consortium conferences and in-depth individual discussions. RESULTS: Challenges
affecting genomics research implementation in Africa, which are related to
limited resources include ill-equipped facilities, poor accessibility to research
centers, lack of expertise and an enabling environment for research activities in
local hospitals. Challenges related to the research study include delayed
funding, extensive procedures and interventions requiring multiple visits, delays
setting up research teams and insufficient staff training, language barriers and
an underappreciation of cultural norms. While many African countries are
struggling to initiate genomics projects, others have set up genomics research
facilities that meet international standards. CONCLUSIONS: The lessons learned in
implementing successful genomics projects in Africa are recommended as strategies
to overcome these challenges. These recommendations may guide the development and
application of new research programs in low-resource settings.
PMID- 29336238
TI - SIRT1-Regulated Abnormal Acetylation of FOXP3 Induces Regulatory T-Cell Function
Defect in Hashimoto's Thyroiditis.
AB - BACKGROUND: Hashimoto's thyroiditis (HT) is an autoimmune thyroid disease
characterized by low expression of transcription factor Forkhead Box P3 (FOXP3)
and functional deficiency of a cluster of differentiation regulatory T cells
(Tregs). This study aimed to investigate the mechanism of Treg dysfunction in HT.
METHODS: The number of CD4+CD25+FOXP3+ T cells was determined by flow cytometry.
Expression of FOXP3 and Sirtuin type 1 (SIRT1) was evaluated by Western blot
analysis. Acetylation of FOXP3 was analyzed by immunoprecipitation and Western
blot analysis. The suppressive function of Treg was analyzed by the 5,6
carboxyfluorescein diacetate succinimidyl ester (CFSE) assay. RESULTS: The
percentage of CD4+CD25+FOXP3+ T cells, expression of FOXP3, and FOXP3 acetylation
level in the HT group were significantly lower than in the control groups.
Conversely, SIRT1 expression was significantly higher in the HT group than in the
other two groups. After Ex-527 treatment, the CD4+CD25+FOXP3+ T cells percentage,
FOXP3 expression, and FOXP3 acetylation level in the HT group were significantly
increased. HT Tregs exhibited less suppressive activity, but Ex-527 treatment
significantly increased their suppressive activity. CONCLUSIONS: The findings
demonstrate that the reduced FOXP3 expression level and Treg function defect in
HT patients are regulated by SIRT1-mediated abnormal FOXP3 acetylation. Ex-527
may upregulate the FOXP3 acetylation level and subsequently increase the number
and suppressive function of Treg cells.
PMID- 29336239
TI - Early prognosis and predictor analysis for positive coronary angiography after
out-of-hospital cardiac arrest (OHCA).
AB - BACKGROUND: Key predictors of survival after OHCA have been described in the
literature. Current guidelines recommend emergency angiography in patients
without an obvious extra-cardiac cause of arrest. However, the value of this
strategy is debated. Moreover, diagnosis of acute coronary ischaemia after OHCA
remains challenging, especially in patients without ST-segment elevation.
OBJECTIVES: The primary objective was to identify qualitative variables
associated with an increased chance of 30-d survival after OHCA. The secondary
objective was to identify predictors of 30-d survival among patients with
ischaemic cardiomyopathy and patients without ST-segment elevation. Afterwards,
we sought to identify parameters associated with acute coronary ischaemia and
positive coronary angiography in patients without ST-segment elevation. METHODS:
Retrospective single-centre study including 123 patients resuscitated from OHCA.
Baseline characteristics, resuscitation settings and angiographic findings were
analysed. RESULTS: The predictors of 30-d survival after OHCA included witnessed
cardiac arrest, haemodynamic instability and coronary angiography. Convertible
cardiac rhythm, history of coronary disease and presence of at least two
cardiovascular risk factors were associated with acute coronary ischaemia.
Predictors for a positive angiography in patients without ST-segment elevation
included history of coronary disease, gender, diabetes, dyslipidaemia and
presence of at least two cardiovascular risk factors (all p < .05). CONCLUSIONS:
We identified qualitative predictors of 30-day survival after OHCA. Our findings
suggest that the recognition of acute coronary ischaemia after OHCA might be
improved. The identification of risk criteria may help to select the best
candidates for emergency angiography.
PMID- 29336240
TI - Treatment of anemia in patients with solid tumors receiving chemotherapy in
palliative setting: usual practice versus guidelines.
AB - Background Anemia is frequent in patients with cancer and is often
multifactorial. Treatment depends on etiology and can consist of transfusions,
intravenous iron (IV Fe), and/or erythropoiesis-stimulating agents (ESA). Several
studies have shown that cancer-related anemia is undertreated. The aim of this
study is to compare usual practice in a university hospital with the
international guidelines. Methods Using the hospital and pharmacy informatics all
adults (>=18 years), who received a treatment for anemia (transfusion, IV Fe,
ESA) from February to August 2016 during palliative chemotherapy, were
identified. Episodes of care were defined as the start of palliative chemotherapy
up until 4 weeks after end of chemotherapy. After informed consent, relevant data
in the episode of care were collected. Usual practice was compared to
international guidelines adapted to Belgium reimbursement criteria. Results A
total of 72 episodes of care were included. At initiation of chemotherapy, anemia
was present in 59.7% of cases. Iron status was measured in 54.2% of all cases.
Iron deficiency was found in 34.7% of patients. Only 52% of the iron deficient
patents received IV Fe. Fifteen cases were considered eligible for ESA, six (40%)
of these patients received an ESA. The most frequent treatments for anemia were
transfusions (91.7%), followed by IV Fe (18.1%). Only 8.3% received an ESA.
Conclusion Assessment for iron, Vitamin B12, and FA deficits are underused. We
detected a high rate of transfusions. In contrast there is still a low use of IV
Fe and ESA's. There has been no major improvement in the implementation of the
international guidelines in the last decade. We estimate that in at least 16.7
26.4% of our patients less to no transfusions would have been required, if
guidelines were strictly followed.
PMID- 29336241
TI - Generation of the Fluorescent HPV16 E7 Protein for Detection of Delivery In
vitro.
AB - BACKGROUND: Immunotherapies targeting the human papillomavirus (HPV) oncogenic
proteins, E6 and E7, are effective to treat HPV-associated cervical malignancies.
OBJECTIVE: The main objective of this study was to generate the fluorescent HPV16
E7 protein for detection of delivery in vitro. METHODS: Two types of the fusion
E7-GFP proteins (i.e., with or without linker) were expressed in different E.
coli strains. Then, the efficiency of GFP and E7-GFP transfection was compared
with FITC-antibody protein control using TurboFect reagent in the HEK-293T cell
line. RESULTS: Our data indicated that both E7-GFP fusion proteins were
efficiently produced in M15 E. coli strain, but not in BL21 or Rosetta strains.
The E7-GFP fusion showed a clear band of ~ 50 kDa in SDS-PAGE. Moreover, the E7
GFP protein maintained the fluorescent properties only when there was a distance
between E7 and GFP genes, suggesting a promising potential to use GFP fusion
protein in generating soluble form of protein. This fluorescent property was
stable and could be detected in vitro. Moreover, the HEK-293T cells transfected
by GFP/TurboFect and E7- GFP/TurboFect complexes demonstrated spreading green
regions using fluorescent microscopy. Flow cytometry results showed that the GFP
fluorescence was stable even at 24 h post-transfection. CONCLUSION: Briefly, the
E7-GFP fusion protein with linker can be useful for the development of protein
vaccines against HPV16 infections and detection in vivo.
PMID- 29336242
TI - The Influence of Fatty Acids on Metoprolol - Human Serum Albumin Interaction in
Low Affinity Binding Sites: A Multifactorial NMR Approach.
AB - BACKGROUND: Metoprolol (MTP) is a cardio-selective beta1-blocker used in
hypertension, angina pectoris and chronic heart failure therapies. Serum albumin
is the most frequently occurring protein in blood plasma. The binding of ligands
to human serum albumin (HSA) has an important effect on pharmacokinetics and
final clinical effects. OBJECTIVE: The objectives of this study included a
detailed analysis of metoprolol - serum albumin interactions in low affinity
binding sites, on the surface or within the hydrophobic subdomain of a
macromolecule, as well as an analysis of the competition between MTP and fatty
acids in binding with protein. METHODS: The analysis of the drug-albumin
interaction was based on the observed chemical shifts in combination with
correlation Times (T1 -1 = tau) [1/s], 2D NOESY 1H NMR spectra and association
constants Ka [M-1]. For the determination of chemical shifts sigma [ppm],
relaxation times T1 [s] and for the NOESY experiment, the final concentrations of
MTP and albumins (in the presence (HSA) and absence of fatty acids (dHSA)) were 5
x 10-3 M and 2 x 10-5 M - 4.55 x 10-4 M, respectively. In order to calculate the
association constants, the final concentrations of MTP and both HSA and dHSA were
2.75 x 10-3 M - 6.25 x 10-2 M and 2.5 x 10-4 M, respectively. For the analysis,
the MTP proton resonances of aliphatic H17, aromatic (H2/H6 and H3/H5) and the
methoxy group H14 were chosen. RESULTS: Changes in the values of the 1H NMR
chemical shift [ppm] are evidence of interaction between MTP, fatted (HSA) and
defatted (dHSA) human serum albumin. With an increase of albumin concentration,
changes in the chemical shift values were observed for the aromatic protons H2/H6
(Deltasigma = 0.013 ppm and 0.018 ppm) and H3/H5 (Deltasigma = 0.015 ppm and
0.019 ppm), the aliphatic proton H17 (Deltasigma = 0.018 ppm and 0.022 ppm) and
the aliphatic protons of the methoxy group H14 (Deltasigma = 0.019 ppm and 0.022
ppm) for dHSA and HSA, respectively. Greater changes in chemical shifts in the
presence of fatty acids (FA) were observed. Changes in the correlation times of
MTP aromatic H2/H6 (Deltatauc = 0.224 1/s and 0.189 1/s) and H3/H5 (Deltatauc =
0.269 1/s and 0.210 1/s), aliphatic from the methoxy group H14 (Deltatauc = 0.472
1/s and 0.271 1/s) and aliphatic H17 protons (Deltatauc = 0.178 1/s and 0.137
1/s) for dHSA and HSA systems, respectively. It confirms the interaction between
the drug and albumin are evidence for the dynamics of the process. In the
presence of FA the relaxation time of all analyzed MTP proton resonance signals
significantly increases (due to the decrease of correlation time). This
phenomenon is due to the increase of electron density in the MTP protons'
surroundings. Association constants for the MTP-dHSA complex in the low affinity
site range between 0.29 x 102 M-1 and 0.47 x 102 M-1. The presence of FA results
in a two to three-fold increase of the Ka values of protons from aromatic (H2/H6
and H3/H5), aliphatic H17 and methoxy (H14) groups. In 2D NOESY spectra proton
magnetization transfer was observed between cysteine (Cys-34) and aromatic H3/H5
and H2/H6 protons. Cross-peaks were also observed between cysteine and aliphatic
protons from the methoxy group. CONCLUSION: The selective changes in sigma [ppm]
and tauc [1/s] values indicated the unequal participation of chemical groups of
MTP in the interaction with HSA and dHSA. The data obtained suggest that the
presence of fatty acids increases the accessibility of low affinity sites of
serum albumin to MTP, which results in the higher affinity of albumin towards the
drug. The results showed that the main binding site of MTP and fatty acid is
probably a low affinity site in subdomain IB, where Cys-34 can be located.
PMID- 29336243
TI - Identification of In-Vitro Red Fluorescent Protein with Antipathogenic Activity
from the Midgut of the Silkworm (Bombyx Mori L.).
AB - BACKGROUND: The midgut of silkworm (Bombyx mori L.) plays an important role as a
natural barrier and source of innate immunity. We had purified the novel red
fluorescent protein (RFP) from the midgut of the silkworm Bombyx mori L. and
bioassay studies confirmed RFPs possess antiviral, antifungal and antibacterial
properties. N-terminal sequence of RFP analysis predicted chbp gene and it
belongs to lipocalin gene family and is known to involve in anti-pathogenic
activities. OBJECTIVE: The main objective of this study was to purify RFP from
the midgut of Kolar Gold silkworm and confirm its antimicrobial activity.
METHODS: For isolation of RFP, midgut juice was collected by brief exposure to
chloroform vapours to fifth instar Kolar Gold silkworm larvae. Juice was purified
by 40 % ammonium sulfate precipitation and purified by gel filtration
chromatography (GFC) and fractions with fluorescence red under Ultra violet (UV)
were collected. Molecular weight and purity of RFP was identified using PAGE,
MALDI-TOF and HPLC. Antimicrobial property of purified RFP against BmNPV,
Escherichia coli, Klebsiella pneumonia, Bacillus subtilis and Phytophthora meadii
was performed. N-terminal sequencing of RFP was performed using Edman degradation
method. Using ten amino acid sequence, using default parameter BLAST search was
performerd. From the fifth day old fifth instar silkworm midgut mRNA was isolated
and cDNA was synthesized using oligo-dt primer and amplification of ChBP gene was
carried out by using cDNA as the template and ChBP gene specific primers. chbp
protein sequence as a input built the homology model by using SWISS-MODEL.
RESULTS: RFP was purified by 40 % ammonium sulfate precipitation and gel
filtration chromatography (GFC) and fractions with fluorescence red under Ultra
violet (UV) were collected and SDS - PAGE revealed a size of 40 kDa. RFP purified
by GFC was further reconfirmed by HPLC with a single peak with a retention time
of 8.755 min. MALDI-TOF produced a peak at a molecular mass of 40 kDa. RFP from
the midgut juice showed antiviral activity against the silkworm virus BmNPV,
antibacterial activity against Escherichia coli, Klebsiella pneumonia, Bacillus
subtilis and Phytophthora meadii. N-terminal sequencing of RFP by Edman
degradation method sequenced TQTIETDYWV amino acids and BLAST analysis predicted
the Chlorophyllide-a Binding Protein (chbp) with B. mori. PCR product was
sequenced and obtained 911bp nucleotides encoding 302 amino acid residues and
deposited with the accession number KX186723 in NCBI. Sequence analysis revealed
Chbp belongs to lipocalin gene family and known to involve in antiviral,
antifungal and anti-bacterial properties. Chbp gene homology model was predicted
using crystal structure of insecticyanin A from the tobacco hornworm as a
template. CONCLUSION: Our results indicated RFP present in midgut juice of 5th
instar larvae of kolar gold silkworm. We have purified novel RFP with molecular
mass of 40 kDa and showed its antipathogenic activities. Chbp gene synthesises
RFP and further it could be utilized for agriculture and pharmaceutical industry.
PMID- 29336244
TI - Editorial: Signal Proteins Involved in Glucose and Lipid Metabolism Regulation.
PMID- 29336245
TI - The Role of Colchicine in Pericardial Syndromes.
AB - BACKGROUND: Colchicine is an old drug originally employed for the treatment of
inflammatory disorders such as acute gout and familiar Mediterranean fever.
METHODS: In the past few decades, colchicine has been at the forefront of the
pharmacotherapy of several cardiac diseases, including acute and recurrent
pericarditis, coronary artery disease, prevention of atrial fibrillation and
heart failure. In this review, we have summarized the current evidence based
medicine and guidelines recommendations in the specific context of pericardial
syndromes. RESULTS: Colchicine has been firstly engaged in the treatment of
recurrent pericarditis of viral, idiopathic and autoimmune origin. Shortly
thereafter colchicine use has been expanded to the primary prevention of
recurrences in patients with a first episode of pericarditis depicting similarly
good results. The acquisition of high quality scientific data in the course of
time from prospective randomized placebo-controlled trials and metanalyses have
established colchicine as first line treatment option in acute and recurrent
pericarditis, on top of the conventional treatment. The only concerns related to
the use of colchicine are the side effects (mainly gastrointestinal intolerance)
which although generally not serious, may account for treatment withdrawal in
some cases. CONCLUSION: Colchicine has been established as a first line
medication in the treatment of acute (first episode) and recurrent pericarditis
on top of the conventional treatment as well as for the prevention of
postpericardiotomy syndrome. It depicts a good safety profile with
gastrointestinal intolerance being the most common side effect.
PMID- 29336246
TI - The Role of Colchicine in the Prevention of Cerebrovascular Ischemia.
AB - INTRODUCTION: Despite the proven efficacy of anti-thrombotic, lipid-lowering,
anti-hypertensive therapies and lifestyle modification changes for secondary
ischemic stroke prevention, the risk of recurrent stroke, coronary events and
vascular death remains substantial even for patients treated with high rates of
established secondary preventive medications. METHODS: In the present review, we
summarize available literature data on the association between systemic
inflammation and symptomatic atherosclerosis including recurrent cerebral
ischemia. We also highlight the potential role of colchicine in the suppression
of atherosclerosis-induced inflammation, plaque stabilization and thromboembolism
prevention. RESULTS: Accumulating evidence suggests that inflammation is of key
importance in the pathophysiology of atherosclerotic plaque de-stabilization and
thromboembolism, with inflammatory cells being involved in all stages of
atherosclerosis development. Therefore, anti-inflammatory therapies targeting the
atherosclerotic plaque inflammation may be important contributors in plaque
stabilization and in the prevention of thromboembolic events. Colchicine is known
to have multiple anti-inflammatory properties including inhibition of microtubule
polymerization, leading to reduced secretion in monocyte-macrophages. Currently
the randomized controlled CONVINCE trial is enrolling stroke patients to evaluate
the effect of a daily low-dose of colchicine in reducing the rate of recurrent
stroke and major vascular events. CONCLUSION: Inflammatory pathways seem to be
key mediators in the development of atherosclerotic process, atheromatous plaque
destabilization and thromboembolism. Colchicine as a novel therapeutic agent
could be a safe and effective inhibitor of the inflammation cascade in patients
with extra- or intracranial atherosclerosis or arteriolosclerosis, resulting in
reduced vascular events.
PMID- 29336247
TI - The Role of Colchicine in the Treatment of Autoinflammatory Diseases.
AB - Colchicine has been longstanding and widely used for the treatment of acute gout
flares and prevention of gout relapses. Its use has been extended to a series of
autoinflammatory diseases, such as familial Mediterranean fever and more recently
to periodic fever with aphthous stomatitis, pharyngitis and adenitis, Behcet's
disease and idiopathic recurrent acute pericarditis. In this review, we summarize
current indications of colchicine use, discuss its pharmacokinetics and mechanism
of action and examine its use in the treatment of autoinflammatory diseases.
Further understanding of the underlying mechanisms of the latter conditions as
well as identification of the therapeutic efficacy and treatment target of
colchicine may lead to more effective management of these diseases.
PMID- 29336248
TI - Immunotheraphy in Allergic Diseases.
AB - The prevalence of allergic diseases is increasing worldwide. It is estimated that
more than 30% of the world population is now affected by one or more allergic
conditions and a high proportion of this increase is in young people. The
diagnosis of allergy is dependent on a history of symptoms on exposure to an
allergen together with the detection of allergen-specific IgE. Accurate diagnosis
of allergies opens up therapeutic options. Allergen specific immunotherapy is the
only successful disease-modifying therapy for IgE-mediated allergic diseases. New
therapeutic strategies have been developed or are currently under clinical
trials. Besides new routes of administration, new types of allergens are being
developed. The use of adjuvants may amplify the immune response towards tolerance
to the antigens. In this review, we analyze different antigen-specific
immunotherapies according to administration route, type of antigens and
adjuvants, and we address the special case of food allergy.
PMID- 29336249
TI - Mutations of Nuclear and Mitochondrial Genomes as Potential Targets for the
Treatment of Metabolic Syndrome.
AB - In addition to external factors, such as exercise, food and the environment,
genetic predisposition makes great contribution to the development of metabolic
disorders and cardiovascular disease. This review is aimed to examine the genetic
basis of complex metabolic disorders conventionally described as "metabolic
syndrome" (MetS), with the special focus on currently known mutations in the
nuclear and mitochondrial genomes, which are associated with both the individual
components of MetS and combinations thereof, and also on the studies of the
relationship of MetS phenotype as a binary trait. The defects in the
mitochondrial genome should be considered as one of the possible genetic reasons
leading to MetS. It is known that mitochondrial dysfunction is closely associated
with metabolic disorders, as mitochondria are the center of energy metabolism.
Consequently, the changes in mitochondrial genes and their functions affect
regulation of metabolism. Until now, the role of mitochondrial DNA damage in the
development of cardiovascular diseases, age-related and metabolic disorders is
still poorly understood. The results of performed studies would help assessing
the role of mitochondrial DNA mutations in susceptibility to metabolic syndrome
and related metabolic diseases.
PMID- 29336250
TI - Colchicum Genus in the Writings of Ancient Greek and Byzantine Physicians.
AB - The plants of the Colchicum family were known during the archaic period in Greece
for their deleterious properties. Later on, they were used for the treatment of
podagra. The treatment was introduced by the ancient Greek physicians and passed
on to the Byzantine and Arabian physicians to endure until nowadays. The first
plant was most probably named "Medea" from the notorious Colchican witch. As the
most common member of the family blossoms in autumn, the plant was named
Colchicum autumnale. Various nominations were also used, such as Ephemeron,
Hermodactyl, Anima articulorum and Surugen. Our article discusses them, while at
the same time presents the most notable authorities who have used Colchicum
plants in herbal medicine and toxicology.
PMID- 29336251
TI - Isolating Colchicine in 19th Century: An Old Drug Revisited.
AB - Colchicine is a tricyclic alkaloid extracted from the herbaceous plant Colchicum
autumnale. Known since antiquity for its therapeutic efficacy in the treatment of
gout, colchicine was reintroduced in 19th century pharmacopeia, thanks to the
work of the French chemists and pharmacists Pierre-Joseph Pelletier (1788-1842)
and Joseph Bienaime Caventou (1795-1877) who in 1819, isolated a peculiar
substance in the roots of Colchicum autumnale. In 1833, the substance was further
analyzed by the German pharmacist and chemist Philipp Lorenz Geiger (1785-1836),
who coined the name colchicine. In 1884, the French pharmacist Alfred Houde (1854
1919) produced for the first time pure crystallized colchicine in granules of
1milligram which is still sold under this trade name in several countries. In the
last two centuries, colchicine's indications were furthermore expanded. From anti
gout drug during antiquity and a diuretic in 19th century, colchicine is
currently administered in several affections such as Adamantiades-Behcet's
disease, familial Mediterranean fever, pericarditis and atrial fibrillation.
PMID- 29336252
TI - Colchicine in Gout: An Update.
AB - Despite the fact that colchicine is by far the most ancient treatment for gout,
new data are still being gathered. In gout, colchicine's ability to block
polymerization of tubulin prevents the activation of the inflammasome. Efficacy
of colchicine for the treatment of gout flares has been demonstrated only
recently by a randomized- controlled trial, but it still has not been compared to
other drugs. Use of colchicine is impaired by the impact of underlying comorbid
conditions and drug interactions that can considerably modify its
pharmacokinetics and pharmacodynamics. This manuscript reviews the state-of-the
art of colchicine in gout, from its known mechanisms of action to its effects,
wanted and unwanted, expected and unexpected.
PMID- 29336253
TI - Colchicine in Post-operative Atrial Fibrillation: A Review.
AB - Post-operative atrial fibrillation (POAF) is a frequent entity increasing
hospitalization duration, stroke and mortality. In the recent years, a few
studies have sought to investigate the potential effect of colchicine in POAF
prevention after cardiac surgery or catheter pulmonary vein isolation for AF. In
the present review article, we intend to provide a synopsis of clinical practice
guidelines, summarize and critically approach current evidence for or against
colchicine as a means of POAF prevention.
PMID- 29336254
TI - Colchicine in Neurosurgery.
AB - BACKGROUND: Colchicine is an ancient drug. Many uses have been reported in
medical books and reports through the centuries. Currently the understanding of
its mechanism of action has opened new horizons to its use. OBJECTIVE: This
article aims to discuss the use of colchicine in various neurosurgical
conditions. METHODS: A pubmed database and clinical trials search was performed,
using the key words "colchicine", "Neurosurgery", "low back pain", "stroke" and
glioma". RESULTS: Various reports were found contemplating the use of colchicine
in chronic low-back pain. The effect of the drug on neutrophil chemotaxis and its
role as an anti-inflammatory agent has been the main argument upon which such use
of colchicine has been structured. These characteristics have been the key to
initiate colchicine as a preventive agent in vascular conditions. Furthermore, as
colchicine is an antimitotic drug, it is currently being studied as a potential
anti-glioma agent. However, the narrow therapeutic index of the drug is a
discouraging factor in clinical application of colchicine in these entities.
Therefore, colchicine derivatives that can exert the same effectiveness in lower
doses are being studied, forming a new direction in colchicine use. CONCLUSION:
Colchicine is a drug that over the years has shown promising results in certain
neurosurgical entities. Its derivatives or potential colchicine-like agents might
have a more significant place in neurosurgical practice.
PMID- 29336255
TI - Fast Screening Technology for Drug Emergency Management: Predicting Suspicious
SNPs for ADR with Information Theory-based Models.
AB - OBJECTIVE: The genetic polymorphism of Cytochrome P450 (CYP 450) is considered as
one of the main causes for adverse drug reactions (ADRs). In order to explore the
latent correlations between ADRs and potentially corresponding single-nucleotide
polymorphism (SNPs) in CYP450, three algorithms based on information theory are
used as the main method to predict the possible relation. METHODS: The study uses
a retrospective case-control study to explore the potential relation of ADRs to
specific genomic locations and single-nucleotide polymorphism (SNP). The genomic
data collected from 53 healthy volunteers are applied for the analysis, another
group of genomic data collected from 30 healthy volunteers excluded from the
study are used as the control group. The SNPs respective on five loci of
CYP2D6*2,*10,*14 and CYP1A2*1C, *1F are detected by the Applied Biosystem 3130xl.
The raw data is processed by ChromasPro to detect the specific alleles on the
above loci from each sample. The secondary data are reorganized and processed by
R combined with the reports of ADRs from clinical reports. Three information
theory based algorithms are implemented for the screening task: JMI, CMIM, and
mRMR. If a SNP is selected by more than two algorithms, we are confident to
conclude that it is related to the corresponding ADR. The selection results are
compared with the control decision tree + LASSO regression model. RESULTS: In the
study group where ADRs occur, 10 SNPs are considered relevant to the occurrence
of a specific ADR by the combined information theory model. In comparison, only 5
SNPs are considered relevant to a specific ADR by the decision tree + LASSO
regression model. In addition, the new method detects more relevant pairs of SNP
and ADR which are affected by both SNP and dosage. This implies that the new
information theory based model is effective to discover correlations of ADRs and
CYP 450 SNPs and is helpful in predicting the potential vulnerable genotype for
some ADRs. CONCLUSION: The newly proposed information theory based model has
superiority performance in detecting the relation between SNP and ADR compared to
the decision tree + LASSO regression model. The new model is more sensitive to
detect ADRs compared to the old method, while the old method is more reliable.
Therefore, the selection criteria for selecting algorithms should depend on the
pragmatic needs.
PMID- 29336256
TI - Mushrooms as Potent Sources of New Biofungicides.
AB - BACKGROUND: Microfungi are causal agents of numerous diseases and disorders of
agricultural plants, farm mushrooms and animals as well as human, which results
are serious global reduction of the food amount, decrease of life quality, the
severe life-threatening diseases and enormous economic losses. METHODS: In spite
of organism innate ability to combat against pathogens, in invasions of some
pathogens, support of additional antimycotic agents to defence system is
required. Nowadays, common "fighters" against the microfungi are numerous
synthetic fungicides that, besides benefits, have also side effects on host and
environment and can cause the development of fungicide resistance in the
pathogens. Therefore, the creation of new natural fungicides with different modes
of action, strengthening the defense system and increase of organism resistance
to pathogens are the main requirements of modern society. RESULTS: Numerous
mushrooms produce chemically various intra- and extracellular metabolites with
antifungal potential, among which the most potent ones are polysaccharides,
proteins, and phenolic compounds. They act as immunostimulators, inhibitors of
pathogen development and virulence and/or activators of pathogens' autolytic
system. CONCLUSION: Therefore, mushroom-based antimycotic agents could be
successfully applied in the diseases treatments as accessories or alternatives to
commercial therapies and in such a way contribute to environmentally friendly
combat against pathogens, i.e. decrease or complete substitution of commercial
synthetic fungicides with natural ones.
PMID- 29336257
TI - Medium Optimization for Recombinant Soluble Arginine Deiminase Expression in
Escherichia coli Using Response Surface Methodology.
AB - OBJECTIVE: Optimization of the medium for recombinant arginine deiminase
production in E. coli was performed using response surface methodology. This is
the first study of optimization of recombinant arginine deiminase production in
E. coli by the use of response surface methodology. METHODS: A Mycoplasm arginine
deiminase gene was computationally optimized and inserted into pET-3a (+)
expression vector. The synthetic pET3a-arginine deiminase construct was cloned
and overexpressed in E. coli. The effect of glucose, NH4Cl and MgSO4.7H2O
concentrations on the expression of intracellular soluble arginine deiminase was
investigated using central composite design (CCD). RESULTS: The maximum arginine
deiminase activity (U/mL) was obtained in optimal concentrations g/L of glucose,
6.6; NH4Cl, 1.81; MgSO4.7H2O, 0.94; KH2PO4, 3.0; Na2HPO4, 6.78; NaCl, 0.5; CaCl2,
0.1 mL/L (1M), which was about 6.6 fold higher than that in M9 standard medium.
CONCLUSION: The obtained result can be utilized for large-scale production of
this enzyme and related recombinant protein.
PMID- 29336258
TI - Association of Thrombospondin-1 (N700S) and Thrombospondin-4 (A387P) Gene
Polymorphisms with the Incidence of Acute Myocardial Infarction in Egyptians
AB - BACKGROUND: Thrombospondin (TSP) 1 and 4 are extracellular matrix glycoproteins
that me-diate cell proliferation, platelet aggregation and inflammatory response.
Conflicting data addressed thepossible contribution of TSP-1 and TSP-4 gene
polymorphisms to acute myocardial infarction (AMI). OBJECTIVE: Our study aimed to
examine the association of TSP-1 (N700S) and TSP-4 (A387P) geneticvariants with
the incidence of AMI in Egyptians. It also correlated TSP-1 variants to TSP-1 and
TNF-alphaserum concentrations while TSP-4 variants to IL-8 concentration
identifying TSPs' contribution to vascular inflammation. METHODS: Genotyping was
done in 214 subjects; 114 AMI patients and 100 controls using PCR-RFLPanalysis.
Serum Tsp-1, TNF-alpha and IL-8 levels were measured by ELISA assay. RESULTS: For
TSP-4, (GC and CC) genotype distribution and the (C) allele frequency were
significantlyhigher in AMI patients than controls (p = 0.0186), (p = 0.0117)
respectively. In contrast, TSP-1 genotypesand allele frequencies showed no
significant difference between AMI and controls (p = 0.7124 and p =0.7201,
respectively). Serum TSP-1, TNF-alpha and IL-8 concentrations were significantly
elevated in AMIcompared to controls (p = 0.0146, p < 0.0001 and p = 0.0057)
respectively. Serum IL-8 levels had a significant difference among TSP-4
genotypes (p= 0.0368), being highest in the mutant C allele. SerumTSP-1 and TNF
alpha concentrations showed no significant difference among TSP-1 genotypes, but
therewas a positive correlation between both concentrations in AMI patients (p =
0.0014), (r = 0.4125). CONCLUSION: TSP-4 A387P polymorphism, but not TSP-1
polymorphism, is an independent risk factorfor AMI in the Egyptians.
PMID- 29336259
TI - p53 as the Focus of Gene Therapy: Past, Present and Future.
AB - BACKGROUND: Several gene deviations can be responsible for triggering oncogenic
processes. However, mutations in tumour suppressor genes are usually more
associated to malignant diseases, with p53 being one of the most affected and
studied element. p53 is implicated in a number of known cellular functions,
including DNA damage repair, cell cycle arrest in G1/S and G2/M and apoptosis,
being an interesting target for cancer treatment. OBJECTIVE: Considering these
facts, the development of gene therapy approaches focused on p53 expression and
regulation seems to be a promising strategy for cancer therapy. RESULTS: Several
studies have shown that transfection of cancer cells with wild-type p53
expressing plasmids could directly drive cells into apoptosis and/or growth
arrest, suggesting that a gene therapy approach for cancer treatment can be based
on the re-establishment of the normal p53 expression levels and function. Up
until now, several clinical research studies using viral and non-viral vectors
delivering p53 genes, isolated or combined with other therapeutic agents, have
been accomplished and there are already in the market, therapies based on the use
of this gene. CONCLUSION: This review summarizes the different methods used to
deliver and/or target the p53 as well as the main results of therapeutic effect
obtained with the different strategies applied. Finally, the ongoing approaches
are described, also focusing on the combinatorial therapeutics to show increased
therapeutic potential of combining gene therapy vectors with chemo or
radiotherapy.
PMID- 29336260
TI - Adipocytes and Abdominal Aortic Aneurysm: Putative Potential Role of Adipocytes
in the Process of AAA Development.
AB - BACKGROUND: Adipose tissue plays a role in the storage of excess energy as
triglycerides (TGs). Excess fat accumulation causes various metabolic and
cardiovascular diseases. It has been reported that ectopic fat deposition and
excess TG accumulation in non-adipose tissue might be important predictors of
cardiometabolic and vascular risk. For example, ectopic fat in perivascular
tissue promotes atherosclerotic plaque formation in the arterial wall. OBJECTIVE:
Recently, it has been reported that ectopic fat (adipocyte) in the vascular wall
of an abdominal aortic aneurysm (AAA) is present in both human and experimental
animal models. The pathological significance of adipocytes in the AAA wall has
not been fully understood. In this review, we summarized the functions of
adipocytes and discussed potential new drugs that target vascular adipocytes for
AAA treatment. RESULT: Previous studies suggest that adipocytes in vascular wall
play an important role in the development of AAA. CONCLUSION: Adipocytes in the
vascular wall could be novel targets for the development of AAA therapeutic
drugs.
PMID- 29336261
TI - Formulation and Investigation of a Lipid Based Delivery System Containing
Antimicrobials for the Treatment of Periodontal Disease.
AB - BACKGROUND: Periodontitis is a chronic inflammatory disease, which affects the
supporting tissues of the teeth, and without proper treatment it may lead to
tooth loss. Antibiotics - administered orally - have been widely used in the
treatment of periodontitis. With the conventional administration routes, adequate
drug levels cannot be reached in the periodontal pockets and oral application of
antimicrobials could lead to side effects. Drug delivery systems containing
antibiotics, administered at the site of infection, could possibly help eliminate
pathogen bacteria and treat periodontitis. OBJECTIVE: The aim of the recent study
was to create a locally swellable, biodegradable, biocompatible, mucoadhesive,
lipophilic drug delivery system containing antimicrobial drugs which softens at
body temperature, accommodate to the shape of the periodontal pocket and can
provide extended drug release for at least one week. METHODS: During the
formulation, thermoanalytical, consistency, wettability, swelling, degradation
and drug release studies were applied to determine the ideal ratios of lipid
bases, structure-building components and surface active agent concentrations.
RESULTS AND DISCUSSION: The structure-building component cetostearyl alcohol
appeared to be the most convenient, thanks to its wettability and mechanical
properties, which led to controlled drug release. With the use of ideal
concentrations of components (10% surfactant, 40% structure-building component,
32 % lipid base, 15% antimicrobial agent and 3% polymer), sustained drug release
can be provided up to nearly 3 weeks.
PMID- 29336262
TI - Ethosomes as Novel Vesicular Carrier: An Overview of the Principle, Preparation
and its Applications.
AB - BACKGROUND: In the study of lipid vesicular carriers in permeation enhancement of
drug molecules across skin after the success story of liposomes, ethosomes are a
recent addition. There are a number of published reviews but still, there is a
lack of reviews representing various aspects in a systematic way with a detailed
description of current research works. This review serves to fill this deficiency
along with special emphasize on its preparation methods and applications.
METHODS: Information was collected from previously published literatures which
were represented after analysis in terms of various aspects such as principles,
composition, preparation, mechanism of penetration, modified forms,
characterization, marketed preparations and its applications. RESULT: This review
is represented in an informative and easily understandable way. Basic principles
and background were covered in the introduction section. Composition section
contains the basic components of formulations along with the impact of various
parameters on the characterization of the ethosome. A detailed discussion of all
the methods along with their own utility is elaborately provided. Various aspects
of characterization studies of ethosomes are also discussed. Therapeutic and
cosmetic applications of ethosomes are also outlined here. CONCLUSION: In spite
of having a excellent permeation-enhancing and targeted drug release profile,
ethosome suffers from limited commercialization. Various challenges regarding
their commercialization and product development are also discussed in this review
with an objective of acting as a directional route for the researchers.
PMID- 29336263
TI - In vitro Methods for In vitro-In vivo Correlation (IVIVC) for Poorly Water
Soluble Drugs: Lipid Based Formulation Perspective.
AB - A great number of new drug candidates identified from the discovery pipeline are
poorly water soluble, which is a drawback to bring such candidates into the
pharmaceutical market. Formulating these compounds as self
emulsifying/microemulsifying/ nanoemulsifying drug delivery systems
(SEDDS/SMEDDS/SNEDDS) within lipid based formulations is of growing interest.
Some of the recent studies have resulted in commercial products that provided
improved bioavailability and dissolution due to the better dispersion properties
of SEDDS/SMEDDS/SNEDDS. An ongoing challenge that the pharmaceutical industry is
facing is identifying in vitro tests that are needed in order to predict the
behavior of dosage forms in the GI tract. The goal of the current review is to
present the various levels of in vitro-in vivo correlations (IVIVCs) and to
provide tools on the utilization of the IVIVCs in product development and
optimization of SEDDS/SMEDDS/SNEDDS.
PMID- 29336264
TI - Taxifolin: Evaluation Through Ex vivo Permeations on Human Skin and Porcine
Vaginal Mucosa.
AB - BACKGROUND: Taxifolin (TAX) is a flavonoid that has numerous pharmacological
properties, including an antioxidant ability superior to that of other flavonoids
due to its particular structure. Nevertheless, it has low oral bioavailability,
which limits its therapeutic application. In this context, potentially important
approaches for systemic drug delivery could be by alternative routes such as skin
and vaginal mucosa, once both routes have a variety of advantages compared with
the oral route, including the ability to bypass both first-pass hepatic
metabolism and the consequent degradation in the gastrointestinal tract. Vaginal
delivery could also account for a local effect, or an effect on circumvent
microregion. OBJECTIVE: The major objective of this study was to develop and
validate a high-performance liquid chromatography (HPLC) method for the
determination of TAX in a semisolid dosage forms and then to evaluate ex vivo
permeations across porcine vaginal mucosa and human skin. METHODS: TAX was
incorporated into an oil-in-water emulsion developed previously by our group.
Method for quantification was developed and validated using HPLC. Permeation
through human skin and vaginal porcine mucosa were conducted in Franz-type cells.
RESULTS: The method was precise (CV < 5%), accurate (recovery between 98% and
102%), linear (R2> 0.99), specific, and robust. Permeation experiments through
porcine vaginal mucosa and human skin presented permeated percentages equal to
87.43% and 48.09% (per dose), respectively. CONCLUSION: The results suggest that,
in the matrixes studied, TAX may be able to exert its biological activities
systemically when applied by these routes. Furthermore, it exhibits greater
permeability potential when administered by intravaginal route.
PMID- 29336265
TI - Efficacy of Aloe vera/ Plantago major gel in Diabetic Foot Ulcer: a randomized
double-blind clinical trial.
AB - BACKGROUND: Diabetic foot ulcer (DFU) is one of the most common complications of
diabetic patients. Mostly, non-healing DFU leads to infection, gangrene,
amputation and even death. High costs and poor healing of the wounds need a new
treatment such as alternative medicine. So, the aim of this study was to evaluate
the efficacy of Aloe vera/ Plantago major gel (Plantavera gel) in healing of DFU.
METHODS: Forty patients with DFU enrolled in a double-blind randomized clinical
trial. The patients who were randomly assigned into the intervention group (n =
20), received topical Plantavera gel in addition to the routine cares, whereas
the patients in the control group (n = 20), received topical Placebo gel in
addition to the routine cares. Intervention was done twice a day for 4 weeks in
the both groups. Photography and an evaluation of DFU healing were conducted by a
checklist and then were scored at baseline and at the end of each week. The
collected data was analyzed by SPSS software. RESULTS: At the end of the study,
there was a significant difference between the two groups in terms of total ulcer
score (P<0.001) and Plantavera gel significantly reduced the ulcer surface
comparing with the control group (P=0.039). However, there was not a significant
difference between the two groups (P=0.263) in terms of the ulcer depth. During
this study, no side effect was observed for Plantavera gel in the intervention
group. CONCLUSION: Topical Plantavera gel seems to be an effective, cheap and
safe treatment. Of course, further studies are required to confirm the properties
of the wound healing of this gel.
PMID- 29336266
TI - Design, Synthesis, Evaluation and Computational Studies of Nipecotic Acid
Acetonaphthone Hybrids as Potential Antiepileptic Agents.
AB - BACKGROUND: Nipecotic acid is considered to be one of the most potent inhibitors
of neuronal and glial gamma-aminobutyric acid (GABA) uptake in vitro. However,
nipecotic acid does not readily cross the blood-brain barrier (BBB) following
peripheral administration, owing to its hydrophilic nature. OBJECTIVE: A series
of substituted acetonaphthones tethered nipecotic acid derivatives were designed
and synthesized with an aim to improve the lipophilicity and the blood-brain
barrier (BBB) permeation. METHODS: Synthesized compounds were tested in mice
models of PTZ, pilocarpine, and DMCM induced epilepsy, in vivo. The rota-rod test
was performed to determine the acute neurotoxicity of the potential leads (4a,
4b, and 4i). These potential hybrids were also evaluated for their ability to
cross the BBB by an in vitro parallel artificial membrane permeability BBB assay
(PAMPA-BBB). The leads were subjected to in silico molecular docking and dynamics
studies on homology modelled protein of human GABA (gamma-amino butyric acid)
transporter 1 (GAT1) and prediction of their pharmacokinetic properties. RESULT:
Amongst the synthesized derivatives, compounds 3a, 3b, 3i, 4a, 4b, and 4i
exhibited increased latency of seizures against subcutaneous pentylenetetrazole
(scPTZ) induced seizures in mice. Derivatives 4a, 4b, 4i were more effective
compared to nipecotic acid ester counterparts 3a, 3b and 3i placing the
importance of the presence of free carboxyl group in the centre. The findings
revealed that 4i was comparatively more permeable (Pe= 8.89) across BBB than the
standard tiagabine (Pe= 7.86). In silico studies proved the consensual
interactions of compound 4i with the active binding pocket. CONCLUSION: Some
nipecotic acid-acetonaphthone hybrids with considerable anti-epileptic activity,
drug like properties and the ability to permeate the BBB have been successfully
synthesized.
PMID- 29336267
TI - Stem Cells Derived from Amniotic Fluid: A Potential Pluripotent-Like Cell Source
for Cellular Therapy?
AB - BACKGROUND: Regenerative medicine aims to provide therapeutic treatment for
disease or injury, and cell-based therapy is a newer therapeutic approach
different from conventional medicine. Ethical issues that rose by the utilisation
of human embryonic stem cells (hESC) and the limited capacity of adult stem
cells, however, hinder the application of these stem cells in regenerative
medicine. Recently, isolation and characterisation of c-kit positive cells from
human amniotic fluid, which possess intermediate characteristics between hESCs
and adult stem cells, provided a new approach towards realising their promise for
fetal and adult regenerative medicine. Despite the number of studies that have
been initiated to characterize their molecular signature, research on developing
approaches to maintain and enhance their regenerative potential is urgently
needed and must be developed. AIM: Thus, this review is focused on understanding
their potential uses and factors influencing their pluripotent status in vitro.
CONCLUSION: In short, this cell source could be an ideal cellular resource for
pluripotent cells for potential applications in allogeneic cellular replacement
therapies, fetal tissue engineering, pharmaceutical screening, and in disease
modelling.
PMID- 29336268
TI - Anaplastic Lymphoma Kinase in Glioblastoma: Detection/Diagnostic Methods and
Therapeutic Options.
AB - BACKGROUND: Glioblastoma (GBM) is the most aggressive and common brain tumor in
adults, currently lacking effective life-prolonging and recurrence-preventing
therapy; median survival of GBM patients stands at only 14-16 months. Increasing
lines of evidence indicate that Anaplastic lymphoma kinase (ALK), a druggable
tyrosine kinase receptor over-expressed in GBM, represents a potential
therapeutic target in this tumor. OBJECTIVE: An overview of the state of the art
and the existing recent patents regarding potential exploitation of ALK as a
therapeutic target and/or diagnostic/prognostic factor in GBM. METHOD: Recent
literature and patents focusing on or including ALK pre-clinical and clinical
research in GBM have been identified and reviewed, and are discussed according to
their potential use. RESULTS: Numerous recent ALK-related patents were
identified. They were reviewed/analyzed in relation to previously published
research and categorized based on their potential in GBM: i) diagnosis/
prognosis, ii) drug-based therapeutic targeting of ALK using a single compound or
combination schemes and iii) therapeutic ALK targeting by other means, e.g. ALK
vaccination. CONCLUSION: ALK targeting holds promise as a novel therapeutic
approach in GBM, especially in combination schemes allowing multi-target therapy.
Such schemes may incorporate detection-guided therapy and utilize next generation
inhibitory compounds with improved central nervous system penetration. Moreover,
identification of ALK-mediated molecular pathway(s) related to GBM
carcinogenesis/ pathology and putative therapy resistance is of high priority and
warrants further exploitation.
PMID- 29336269
TI - Design, Synthesis, and Biological Evaluation of New Azole Derivatives as Potent
Aromatase Inhibitors with Potential Effects against Breast Cancer.
AB - PURPOSE: Some aromatase inhibitors are FDA-approved agents as first-line therapy
in the treatment of endocrine-responsive breast cancer. In this study, we aimed
to develop new azole derivatives with higher specificity and potency. METHODS:
New aromatase inhibitors were designed by Molecular Operating Environment (MOE)
software and synthesized in a one-step SN2 reaction. These compounds were
characterized by melting point, 1H- and 13C-NMR, elemental analysis and mass
spectra. The in-vitro and in-vivo aromatase inhibition of these compounds was
evaluated using the Estrone ELISA assay, and by measuring the inhibition of
androstenedione-induced uterine hypertrophy. The selectivity of aromatase
inhibition was investigated by the inhibition of ACTH stimulation on the plasma
concentrations of aldosterone and cortisol. RESULTS: Docking simulations showed
that four new azole derivatives could efficiently interact with enzyme active
sites. The in-vitro aromatase-inhibition assay showed that the compounds 1,3,5
tris(imidazol-1-ylmethyl)benzene (3b) and 1,3-Bis(imidazole-1- ylmethyl) benzene
(3d) effectively inhibited aromatase, with IC50 values of 0.2 nM and 6.8 nM,
respectively; these values were similar to known aromatase inhibitor letrozole
(IC50 0.3 nM). The in-vivo aromatase-inhibitory potency of compound 3b was
similar to letrozole, although compound 3b acted more selectively. CONCLUSION:
This report introduced a new compound that can be considered as a new lead for
further investigation to explore more-potent and more-selective aromatase
inhibitors.
PMID- 29336270
TI - In silico Structure-based Identification of Novel Acetylcholinesterase Inhibitors
Against Alzheimer's Disease.
AB - OBJECTIVE AND BACKGROUND: Inhibition of acetylcholinesterase (AChE) has gained
much importance since the discovery of the involvement of peripheral anionic site
as an allosteric regulator of AChE. Characterized by the formation of beta
amyloid plaques, Alzheimer's disease (AD) is currently one of the leading causes
of death across the world. Progression in this neurodegenerative disorder causes
deficit in the cholinergic activity that leads towards cognitive decline.
Therapeutic interventions in AD are largely focused upon AChE inhibitors designed
essentially to prevent the loss of cholinergic function. The multifactorial AD
pathology calls for Multitarget-directed ligands (MTDLs) to follow up on various
components of the disease. Considering this approach, other related AD targets
were also selected. Structure-based virtual screening was relied upon for the
identification of lead compounds with anti-AD effect. METHOD: Several
chemoinformatics approaches were used in this study, reporting four multi-target
inhibitors: MCULE-7149246649-0-1, MCULE-6730554226-0-4, MCULE-1176268617-0-6 and
MCULE-8592892575-0-1 with high binding energies that indicate better AChE
inhibitory activity. Additional in-silico analysis hypothesized the abundant
presence of aromatic interactions to be pivotal for interaction of selected
compounds to the acetyl-cholinesterase. Additionally, we presented an alternative
approach to determine protein-ligand stability by calculating the Gibbs-free
energy change over time. Furthermore, this allows to rank potential hits for
further in-vitro testing. RESULTS AND CONCLUSION: With no predicted indication of
adverse effects on humans, this study unravels four active multi-target
inhibitors against AChE with promising affinities and good ADMET profile for the
potential use in AD treatment.
PMID- 29336271
TI - Anti-Inflammatory Drugs and Herbs with Special Emphasis on Herbal Medicines for
Countering Inflammatory Diseases and Disorders - A Review.
AB - BACKGROUND: Diseases with inflammatory etiopathology have increased in incidence
in recent times. Drugs used for therapeutic management of such inflammatory
diseases are relieving the ailment but at the same time also countering serious
life threatening consequences. Moreover, they are costly and rarely available at
all places. In this context, research and development on medicinal herbs have
opened a new era in the prophylactic and therapeutic management of inflammatory
diseases. OBJECTIVE: To highlight the importance of anti-inflammatory medicine
synthetic drugs and natural herbs, their constituents, mechanism of action,
benefits, side effects and future prospects. The overall aim is to provide better
health services to patients regardless of their background on equality basis.
RESULTS: Anti-inflammatory herbs have proven beneficial by combating inflammatory
responses that lead to severe abnormality in body systems. Inflammation though a
protective response to infection or injury and may result in pathological outcome
when aggravated or of severe degree thus needs an early intervention for proper
resolution. Medicinal plants or their constituents are considered beneficial due
to the properties i.e., satisfactory potency, ease of availability, cheapness,
less or no side effects, safer and efficient as compared to the synthetic
counterparts. These medicinal herbs contain phytoconstituents that can prevent
undesirable inflammatory processes and also posses anti-inflammatory activity.
Steroids, glycosides, phenolics, flavonoids, alkaloids, polysaccharides,
terpenoids, cannabinoids, fatty acids are common phytoconstituents present in
these plants. Different mechanisms have been explored for the anti-inflammatory
action of these active ingredients. They may synergize the anti-inflammatory
pathway enzymes, factors, proteins or interfere with these in the inflammatory
pathway like lipooxygenases, cyclooxygenases, tumor necrosis factors,
interleukins, prostaglandin, nitric oxide, mitogenactivated protein, nuclear
factor, etc. Considering all the above-mentioned factors, further research from
molecular to cellular level will enable a better understanding of the mechanisms.
Common antiinflammatory herbal plants are Curcuma longa, Zingiber officinale,
Rosmarinus officinalis, Borago officinalis, Urtica dioica, Uncaria tomentosa,
Vaccinium myrtillus, Olea europaea and much more. They are believed to be without
side effects unlike the chemical counterparts or synthetic anti-inflammatory
agents e.g. steroids, nonsteroid anti-inflammatory drugs, and immunosuppresants
used for controlling and suppressing inflammatory crisis. A proper phytochemical,
pharmacological and physiological evaluation will enable their safe and effective
use in inflammatory conditions. Many of these anti-inflammatory drugs and herbal
preparations have been patented with some under consideration. CONCLUSION:
Natural herbs are safe, effective and better options as anti-inflammatory agents
than synthetic ones. The phytoconstituents are as effective with the comparable
mechanism of action as synthetic molecules. Future research should focus on
molecular mechanisms of different beneficial applications of these herbal plants
in various diseases. Recent patents on anti-inflammatory drugs and herbal plants
have been covered which provide insight into the current status and future
prospects in this field.
PMID- 29336273
TI - Medications Are Risky Business.
PMID- 29336272
TI - Let-7 miRNA Precursors Co-express with LIN28B in Cervical Cells.
AB - BACKGROUND: The let-7 microRNAs (miRNAs) are frequently dysregulated in
carcinogenic processes, including cervical cancer. LIN28 proteins regulate let-7
biogenesis by binding to conserved sequences within the pre-miRNA structure.
Nevertheless, recent research has shown that some let-7 miRNAs may escape LIN28
regulation. OBJECTIVE: Correlate pre-let-7 miRNAs and LIN28B levels in cervical
cell lines with different malignancy and HPV content. METHODS: Pre-let-7 levels
were determined by RTqPCR. LIN28B and other let-7 targets were analyzed by
immunoblot. In silico tools were used to correlate let-7 and LIN28B expression
and to analyze prelet- 7 sequences and structures. RESULTS: Lin28B protein was
detected in all tested cell lines although it was more expressed in tumor cell
lines. High levels of pre-let-7c/f-1 and pre-miR-98 were present in almost all
cell lines regardless malignancy and LIN28B expression. Pre-let-7g/i were mainly
expressed in tumor cell lines, pre-let-7e and pre-let-7-a3 were absent in all
cell lines and pre-let-7a-2 showed indistinct expression. LIN28B showed positive
correlation with pre-let-7i/g/f-1 and pre-miR-98 in tumor cell lines, suggesting
escape from regulation. Sequence alignment and analysis of pre-let-7 miRNAs
showed distinctive structural features within the preE region that may influence
the ideal pre-let-7 structuring for LIN28B interaction. Short preE-stems were
present in pre-let-7 that may escape LIN28B regulation, but long preEstems were
mostly associated with high-level pre-let-7 miRNAs. CONCLUSION: The observed
differences of pre-let-7 levels in cervical cell lines may be the result of
alternative preE structuring affecting interaction with LIN28B thus resulting in
differential let-7 regulation.
PMID- 29336274
TI - Controlling Diabetes: Continuous Glucose Monitoring for the Older Adult.
AB - Obtaining and maintaining adequate blood glucose control in the older adult with
diabetes offers unique challenges. Intensive blood glucose control can increase
the risk of hypoglycemia, which can be particularly risky in the older adult.
Adding and adjusting diabetes medications in elderly patients with multiple
comorbidities and numerous other medications can also be challenging. The use of
professional continuous glucose monitors-which are worn by the patient for up to
two weeks and record blood sugars every 5 to 15 minutes-provides pharmacists and
other health care professionals with valuable data for managing the care of the
older adult with diabetes.
PMID- 29336275
TI - Clinical Research That Matters: Designing Outcome-Based Research for Older Adults
to Qualify for Systematic Reviews and Meta-Analyses.
AB - Though older adults are more sensitive to the effects of medications than their
younger counterparts, they are often excluded from manufacturer-based clinical
studies. Practice-based research is a practical method to identify medication
related effects in older patients. This research also highlights the role of a
pharmacist in improving care in this population. A single study rarely has strong
enough evidence to change geriatric practice, unless it is a large-scale,
multisite, randomized controlled trial that specifically targets older adults. It
is important to design studies that may be used in systematic reviews or meta
analyses that build a stronger evidence base. Recent literature has documented a
gap in advanced pharmacist training pertaining to research skills. In this paper,
we hope to fill some of the educational gaps related to research in older adults.
We define best practices when deciding on the type of study, inclusion and
exclusion criteria, design of the intervention, how outcomes are measured, and
how results are reported. Well-designed studies increase the pool of available
data to further document the important role that pharmacists have in optimizing
care of older patients.
PMID- 29336276
TI - Streamlining the Medication Review Process by Use of a New Review Tool: CHART.
AB - OBJECTIVE: The Carlson-Hamilton Adult Medication Review Tool (CHART) represents
an effort to improve the approach to geriatric care by streamlining the
medication review process and identifying potential medication issues that may be
relevant to patient's cognitive presentation and impact clinical decision making.
SETTING: CHART was created at a behavioral health facility. The most common
primary diagnoses on this unit include new onset psychosis and recent mental
status changes. PRACTICE DESCRIPTION: This facility contains 155 beds divided
into six units. The geriatric unit has an average census of 10 patients, with an
average length of stay of 10 to 12 days. PRACTICE INNOVATION: This site is
working to improve geriatric patient care by simplifying and streamlining the
medication review process. MAIN OUTCOME MEASUREMENTS: The pharmacy team evaluated
change in medication burden and change in medication review requests. RESULTS:
Following implementation, this facility saw both a decreased medication burden
and an increase in medication review requests. CONCLUSION: CHART is a tool that
allows pharmacists and student pharmacists to streamline the review of
medications and make recommendations.
PMID- 29336277
TI - Evaluation of Hypoglycemia and Potential Risk Factors in a Veterans Affairs
Community Living Center.
AB - OBJECTIVES: To describe hypoglycemic events in a Veterans Affairs (VA) community
living center (CLC) population and to determine predictive risk factors
associated with hypoglycemia. DESIGN: Retrospective, exploratory, observational
chart review. SETTING: Tertiary-care VA Healthcare System CLC. PATIENTS:
Residents residing in a VA CLC with at least one active order for insulin between
June 1, 2009, and June 30, 2013, were evaluated over a 90-day study period. MAIN
OUTCOME MEASURES: The primary outcome was the number of days to the first
hypoglycemic event as described by the survival curve analysis. The secondary
outcomes included the overall incidence of hypoglycemia, the association of
potential risk factors on the proportion of hypoglycemic events, and the
association of potential risk factors on the development of an additional
hypoglycemic event. RESULTS: There was a 49% incidence of a hypoglycemic event in
the 90-day study period with a 24% incidence within the first 7 days of resident
admission, representing approximately half of all events that occurred. The only
statistically significant risk factor for having a hypoglycemic event was the
number of units of insulin/kg/day (hazard ratio = 1.008, 95% confidence interval
1.001, 1.015; P = 0.0317) that a resident was prescribed. CONCLUSIONS: Residents
are at increased risk for hypoglycemia within the first seven days of admission
to a CLC. It is imperative that providers closely monitor and reevaluate
antidiabetic regimens at this time of transition.
PMID- 29336278
TI - Use of 2015 Beers Criteria Medications by Older Medicare Beneficiaries.
AB - OBJECTIVE: To examine the prevalence of potentially inappropriate medications
(PIMs) in community-dwelling Medicare beneficiaries based on the updated 2015
American Geriatrics Society Beers criteria. DESIGN: Cross-sectional study.
SETTING: Thirteen mobile Medicare clinics were held throughout Northern and
Central California during the fall of 2015. PATIENTS, PARTICIPANTS:
Noninstitutionalized Medicare beneficiaries 65 years of age and older taking one
or more medications. INTERVENTIONS: Pharmacy students under direct supervision of
licensed pharmacists performed medication therapy management (MTM). Drug and
disease state data were collected and used to identify PIMs based on the 2015
Beers criteria. MAIN OUTCOME MEASURES: Number of beneficiaries who are taking a
PIM, have a potential drug-drug or drug-disease interaction, and common factors
associated with receiving a PIM. RESULTS: MTM services were provided to 703
beneficiaries 65 years of age or older taking 1 or more medications. In total,
204 (29%) beneficiaries were taking 1 or more PIM. Drug-drug interactions were
found in 54 beneficiaries, and 12 beneficiaries were found to have a significant
drug-disease interaction. PIM prescribing was associated with certain chronic
conditions (e.g., pain and insomnia). The prevalence of PIM use was significantly
higher in women compared with men, whites compared with non-whites, and low
income beneficiaries compared with high income. CONCLUSION: Prescribers and
pharmacists should work in concert to minimize PIM use in older adults.
Practitioners knowledgeable about the updated 2015 Beers criteria may monitor
drug use more closely, hopefully minimizing potentially harmful drug and/or
disease-state problems, and preventing avoidable health-related sequelae.
PMID- 29336279
TI - CMS Proposes Sweeping Medicare Rule.
PMID- 29336280
TI - Open access: Is there a predator at the door?
PMID- 29336281
TI - Naive and effector B-cell subtypes are increased in chronic rhinosinusitis with
polyps.
AB - BACKGROUND: Recent studies demonstrated that B cells and their chemoattractants
are elevated in the nasal mucosa of patients with chronic rhinosinusitis (CRS)
with nasal polyposis (CRSwNP). However, the presence of naive B cells and of
plasmablasts and memory B-cell subsets in the mucosa and periphery of the same
patient with CRS is yet to be characterized. OBJECTIVE: Here we sought to
quantify naive, plasmablasts, and memory B cells in mucosal tissue and peripheral
blood of patients with CRSwNP, patients with CRS without nasal polyps (CRSsNP),
and control patients. METHODS: Polyps, mucosa, and peripheral blood samples were
prospectively collected from the patients with CRS and from the non-CRS controls.
We used flow cytometry to distinguish among naive, plasmablast, and memory B
cells in sinus tissue and peripheral blood. RESULTS: A total of 45 patients were
recruited for the study. The patients with CRSwNP had significantly increased
mucosal B-cell numbers versus the controls (3.39 +/- 4.05% versus 0.39 +/- 1.05%
of live cells; p < 0.01, Kruskal-Wallis test), which included naive B cells (0.61
+/- 0.94 versus 0.11 +/- 0.24% of live cells; p < 0.03, Kruskal-Wallis test),
plasmablasts (0.06 +/- 0.26 versus 0.00 +/- 0.00% of live cells; p < 0.055,
Kruskal-Wallis test), and memory B cells (0.62 +/- 1.26 versus 0.05 +/- 0.15% of
live cells; p < 0.02, Kruskal-Wallis test). CONCLUSION: Our study identified
increased frequencies of different B-cell subtypes in the mucosa of patients with
CRSwNP but not in the peripheral blood. We also found that patients with CRSwNP
had significantly increased B-cell subtypes compared with the patients with
CRSsNP and the controls. These results implied a potential role for mucosal B
cells in the ongoing inflammation in patients with CRSwNP.
PMID- 29336283
TI - Headaches and facial pain in rhinology.
AB - "Sinus headache" is a common chief complaint that often leads patients to an
otolaryngologist's office. Because facial pain may or may not be sinogenic in
origin, the otolaryngologist should be equipped to evaluate and treat or to
appropriately refer these patients. Analysis of current data indicates that the
majority of patients who present with sinus headaches actually have migraines.
Furthermore, the downstream effect of the cytokine cascade initiated in migraine
physiology can cause rhinologic symptoms, including rhinorrhea, congestion, and
lacrimation, which may also confound diagnosis. Other causes of sinus headache
include the following: cluster headaches, Sluder neuralgia, trigeminal neuralgia,
myofascial trigger point pain (tension headaches, temporomandibular joint
dysfunction), and contact point headaches. The diagnostic dilemma for an
otolaryngologist occurs when a patient has facial pain and symptoms that may
indicate chronic rhinosinusitis but with nondiagnostic endoscopy. Traditionally,
these patients have been primarily managed with empiric antibiotics. An
alternative strategy is to first screen these patients with an upfront computed
tomography. This algorithm may ultimately decrease cost; avert unnecessary
antibiotics prescriptions; and prompt more timely referrals to other, more
appropriate, disciplines, such as neurology, dentistry, and/or pain management
specialists.
PMID- 29336282
TI - Role of group 2 innate lymphocytes in aspirin-exacerbated respiratory disease
pathogenesis.
AB - Aspirin-exacerbated respiratory disease (AERD) is characterized by chronic
eosinophilic nasal polyps, asthma, and airway reactions upon cyclooxygenase (COX)
1 inhibition. AERD is present in up to 7% of adult patients with asthma and the
underlying pathogenesis remains largely elusive but prostaglandin D2, cysteinyl
leukotrienes, mast cells, and type 2 cytokines are thought to contribute. A
wealth of studies have recently implicated group 2 innate lymphoid cells (ILC2),
a novel lineage-negative lymphocyte population that produces type 2 cytokines, in
human allergic disease pathogenesis. Importantly, our recent work identified that
ILC2s are recruited to the nasal mucosa of patients on AERD after COX-1 inhibitor
administration. Here, we review the potential impact of ILC2s in the development
and propagation of type 2 inflammation in AERD.
PMID- 29336284
TI - Assessing the onset of allergic rhinitis by nasal cytology and immunoglobulin E
antibody levels in children.
AB - BACKGROUND: It is difficult to identify the onset of allergic rhinitis in infants
because making a conclusive diagnosis can be challenging. OBJECTIVE: We used a
combination of cell differentials in nasal swabs and immunoglobulin E (sIgE)
antibody values to food and inhalant allergens to make the diagnosis and identify
relevant allergens for investigation of the onset of allergic rhinitis. METHODS:
We studied 302 children, 2 to 120 months old, who visited our clinic for
rhinorrhea. Nasal swabs were taken from all children, and neutrophils (N),
eosinophils (Eo), and mast cells (Mc) were identified by nasal cytology and their
numbers were estimated. Levels of sIgE antibodies to various food and inhalant
allergens were determined in patients with nasal Eo and Mc. RESULTS: Percentages
of participants with Eo-Mc and Eo-Mc-N at 2-14 (n = 84), 15-24 (n = 57), 25-60 (n
= 73), and 61-120 months of age (n = 88) were 20, 23, 58, and 65%, respectively.
There were no significant differences between the 2-14 and 15-24, and 25-60 and
61-120 months age groups, but there was a significant difference between the 15
24 and 25-60 months age groups (p = 0.00013). The percentages of participants
with sIgE antibodies to food and inhalant allergens as solitary or main allergen
were 12%/0% at 2-14 months old, 10.5%/7% at 15-24 months old, 1.3%/42.4% at 25-60
months old, and 0%/56.8% at 61-120 months old, respectively with a significant
difference between 15-24 and 25-60 months old groups (p = 0.00025) for inhalant
allergens. CONCLUSION: Allergic rhinitis associated with inhalant allergens in
infants <15 months of age is rare, but it is tempting to postulate that symptoms
of rhinitis in these infants may be associated with sIgE antibodies to food
allergens. Transition of sIgE responses from food to inhalant allergens occurred
after 15 months of age, and sIgE antibodies to inhalant allergens were
predominant after 25 months.
PMID- 29336285
TI - Optimal cutoff values of allergen-specific immunoglobulin E to house dust mites
and animal dander based on skin-prick test results: Analysis in 16,209 patients
with allergic rhinitis.
AB - BACKGROUND: The most common tests for allergen sensitization in patients with
allergic rhinitis are the skin-prick test (SPT) and an in vitro test to detect
serum specific immunoglobulin E (sIgE). However, in vitro allergen test results
were interpreted dichotomically as positive or negative at a threshold of 0.35
kU/L of sIgE, regardless of the patient characteristics or antigen types.
OBJECTIVE: The purpose of this study was to determine the cutoff value for sIgE
in house-dust mites and animal dander, and to analyze differences in cutoff value
according to age and gender. METHODS: A total of 16,209 patients with more than
one allergic rhinitis symptom who underwent both SPT and serum sIgE testing were
retrospectively evaluated between March 2008 and May 2012. There were 9374 male
(57.8%) and 6835 female (42.2%) patients. The mean age was 31.8 years (range, 2
89 years). The criterion standard for allergen sensitization was defined as a
wheal of >3 mm or an allergen-to-histamine ratio of >=1 in SPT results. The
Youden index was used to calculate the cutoff value of sIgE. RESULTS: Cutoff
values of sIgE for Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat,
and dog were 0.69, 1.16, 0.13, and 0.45 kU/L, respectively. The cutoff value of
sIgE changed according to age for D. pteronyssinus and D. farinae but not for cat
and dog allergens. When categorizing according to age group, the cutoff values of
sIgE for D. pteronyssinus and D. farinae had a tendency to decrease with age.
There was no significant difference in cutoff value according to gender.
CONCLUSION: The cutoff value for sIgE differed for each antigen and changed with
age. Physicians should select the proper cutoff value for sIgE for appropriate
criteria according to antigen and patient age rather than using a uniform cutoff
value.
PMID- 29336286
TI - Oral allergy syndrome.
AB - OBJECTIVES: To review oral allergy syndrome (OAS). METHODS: We searched several
medical literature data bases with the following key words: "oral allergy
syndrome," "OAS," "pollen-food allergy syndrome," "PFAS," "allergy," "diagnosis,"
"treatment." RESULTS: Oral allergy syndrome (OAS), also called "pollen-food
allergy syndrome," is a type of food allergy brought about by flavors, nuts, raw
fruit, and vegetables. The most well-known symptoms are mouth and throat itching,
which starts rapidly after a food is placed in the mouth, and that, as a rule,
continues for just a couple of minutes after the food has been swallowed. The
frequency of OAS with pollen allergy has been reported as 5-8%; 1-2% of patients
with OAS with pollen allergy show extreme responses, e.g., anaphylaxis. Birch
tree pollen, ragweed pollen, and grass pollen hypersensitivity cause the
symptoms. The diagnosis of OAS is confirmed by a positive history and positive
skin-prick test result triggered by the food's fresh extract. Oral challenge
result is normally positive with the raw food and negative with the similar
cooked food. CONCLUSION: Patients with grass allergy may have a response to
peaches, oranges, celery, tomatoes, and melons. Patients with ragweed allergy may
show OAS symptoms with melon, cucumber, banana, and zucchini. Physicians should
be aware of OAS and know the appropriate treatment.
PMID- 29336287
TI - Endoscopically assisted Crawford tube placement results in shorter general
anesthesia times in pediatric patients.
AB - BACKGROUND: Crawford tube placement is commonly used to achieve patency of
nasolacrimal ducts for epiphora secondary to nasolacrimal duct obstruction. The
nasal passages of pediatric patients are narrower than adults, and the result is
a relatively higher risk of intranasal complications (e.g., synechiae, bleeding)
with Crawford tube placement. There is evidence that general anesthesia may
negatively affect the neurocognitive function and behavioral development of
children, which prompts efforts to decrease operation times for potential health
benefits and also potentially to reduce health care costs. Analysis of research
reports supports the use of nasal endoscopy to reduce intranasal complications
with Crawford tube placement; however, no publications currently address the
effect of nasal endoscopy concurrent with Crawford tube placement on operative
times on pediatric patients or the resulting effects on health care costs.
OBJECTIVE: To determine the difference in procedure time and cost between
Crawford tubes placed traditionally and those placed with endoscopic assistance
in pediatric patients. METHODS: A chart review was performed from January 1, 2011
to December 31, 2016 for cases using CPT codes 68815 or 31231. Within this group
of patients, the patient in whom nasal endoscopy was performed were placed in the
"endoscopic" group and the patients without endoscopy were placed in the
"traditional" group. Procedure times were noted, and the t-test was performed to
examine for any statistically significant difference in operative times.
Estimates of anesthesia cost savings were made. We identified 24 patients in the
traditional group and 7 patients in the endoscopic group. RESULTS: The average
operative time for the traditional group was 27.3 minutes compared with 14.0
minutes for the endoscopic group (p = 0.02). The cost comparison data revealed no
significant difference with the traditional group averaging $9369 per procedure
and the endoscopic group averaging $8891 (p = 0.51). CONCLUSION: An
endoscopically assisted Crawford tube placement resulted in patients who had less
time under general anesthesia compared with the traditional technique at no
difference in cost.
PMID- 29336288
TI - How often is sinus surgery performed for chronic rhinosinusitis with versus
without nasal polyps?
AB - BACKGROUND: There currently are no data on the relative frequency of endoscopic
sinus surgeries (ESS) performed for chronic rhinosinusitis with nasal polyposis
(CRSwNP) versus chronic rhinosinusitis without nasal polyposis (CRSsNP) in the
United States. OBJECTIVES: To compare the rate of surgical interventions for
CRSwNP and CRSsNP. METHODS: Cases identified by CPT codes were extracted from the
2009-2011 State Ambulatory Surgery Databases for California, Florida, Maryland,
and New York. Patient demographics, extent of surgery, mean charges, and
operating room (OR) time were compared. RESULTS: A total of 97,228 ESS cases were
performed in the four states; 29.3% of surgeries were for patients with CRSwNP,
66.0% of patients with CRSsNP, and 4.8% for other indications. The proportion of
ESS for CRSwNP varied across states, with California having the highest
percentage (34.6%) and Maryland having the lowest (26.4%) (p < 0.0001). Patients
with Medicaid (33.8%) and Medicare (32.2%) had higher rates of surgery for CRSwNP
compared with patients with private insurance (29.9%) (p < 0.001). Surgeons who
performed a higher volume of sinus surgery compared to lower volume surgeons
performed a lower percentage of surgery for CRSwNP (24.4 versus 33.5%; p <
0.001). ESS cases for CRSwNP were more extensive (relative risk of four sinus
surgeries of 1.88; p < 0.0001), used image guidance more frequently (relative
risk, 1.39; p < 0.0001), and were less likely to include a balloon procedure
(relative risk, 0.69; p < 0.0001). Patients with CRSwNP had longer OR times (ESS
that involved all four sinuses took 14 minutes longer) (p < 0.0001), but no
difference in charges compared with patients with CRSsNP who underwent a similar
extent of surgery. CONCLUSION: Almost 30% of ESS were performed for CRSwNP, and
these cases were, on average, more extensive, used more OR time, and more often
used image guidance than surgeries for CRSsNP. The rate of surgery performed for
CRSwNP varied based on geography, payer, and surgical volume, which indicted that
patient selection impacted surgical management.
PMID- 29336289
TI - Management of odontogenic cysts by endonasal endoscopic techniques: A systematic
review and case series.
AB - BACKGROUND: Odontogenic cysts and tumors of the maxilla may be amendable to
management by endonasal endoscopic techniques, which may reduce the morbidity
associated with open procedures and avoid difficult reconstruction. OBJECTIVE: To
perform a systematic review that evaluates the feasibility and outcomes of
endoscopic techniques in the management of different odontogenic cysts. A case
series of our experience with these minimally invasive techniques was assembled
for insight into the technical aspects of these procedures. METHODS: The
Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used to
identify English-language studies that reported the use of endoscopic techniques
in the management of odontogenic cysts. Several medical literature data bases
were searched for all occurrences in the title or abstract of the terms
"odontogenic" and "endoscopic" between January 1, 1950, and October 1, 2016.
Publications were evaluated for the technique used, histopathology,
complications, recurrences, and the follow-up period. A case series of patients
who presented to a tertiary rhinology clinic and who underwent treatment of
odontogenic cysts by an endoscopic technique was included. RESULTS: A systematic
review identified 16 case reports or series that described the use of endoscopic
techniques for the treatment of odontogenic cysts, including 45 total patients.
Histopathologies encountered were radicular (n = 16) and dentigerous cysts (n =
10), and keratocystic odontogenic tumor (n = 12). There were no reported
recurrences or major complications for a mean follow-up of 29 months. A case
series of patients in our institution identified seven patients without
recurrence for a mean follow-up of 10 months. CONCLUSION: Endonasal endoscopic
treatment of various odontogenic cysts are described in the literature and are
associated with effective treatment of these lesions for an average follow-up
period of >2 years. These techniques have the potential to reduce morbidity
associated with the resection of these lesions, although comparative studies
would better define specific indications.
PMID- 29336290
TI - Comparison between endoscopic and external dacryocystorhinostomy by using the
Lacrimal Symptom Questionnaire: A pilot study.
AB - BACKGROUND: Epiphora has a significant impact on the patient's quality of life
and is commonly caused by nasolacrimal duct obstruction. Dacryocystorhinostomy
(DCR) has traditionally been performed via an external approach, which involves a
skin incision. With the advent of endoscopes, the endonasal approach to DCR has
gained significant popularity. METHOD: To prospectively compare the quality of
life of adult patients who underwent either an endonasal or an external DCR for
acquired nasolacrimal duct obstruction, the Lacrimal Symptom Questionnaire (Lac
Q) was administered before and after surgery. The treatment group assignment was
nonrandom and performed based on patient preference. The Lac-Q is a validated
questionnaire that assesses the subjective perception of one's well-being from an
eye-specific symptom and social impact standpoint. Total scores range from 0 (no
concerns) to 33 (maximal degree of ocular symptoms and social impact). RESULTS:
Sixty patients (22 in the endonasal group, 38 in the external group) were
recruited between January 1, 2014, and January 1, 2016. Postoperative assessment
was performed at 3 and 6 months. Patients who underwent external DCR reported a
median 7.0-point improvement (interquartile range [IQR], 3.0-11.0) in total Lac-Q
scores. A 12.0-point improvement (IQR, 10.0-18.5) was seen in the endonasal group
(p = 0.005). The median change in the social impact score was 3.0 and 4.0 in the
external group and the endoscopic group, respectively (p = 0.029). Changes in the
median lacrimal symptom score were 4.0 in the external group and 8.0 in the
endoscopic group (p = 0.014). The anatomic patency rate was lower in the external
group (60.0%) when compared with the endonasal group (90.4%). Patients in the
external DCR group were significantly older (median age, 51 versus 41 years).
CONCLUSION: Our study indicated that both endonasal and external DCR can lead to
improvement in quality of life by using a validated questionnaire. Although there
are differences in age and anatomic success rates between the two groups,
subgroup analyses indicated that the differences in the Lac-Q scores persisted
when age and anatomic patency were removed as potential confounding factors.
Further larger, randomized studies would be helpful.
PMID- 29336291
TI - Extent of surgery in endoscopic transsphenoidal skull base approaches and the
effects on sinonasal morbidity.
AB - BACKGROUND: Endoscopic transsphenoidal skull base surgery (ETSS) is now
considered the criterion standard approach for resection of pituitary adenomas
and other midline anterior skull base lesions. Normal sinonasal structures are
resected during ETSS, which raises concerns for nasal morbidity and patient-based
outcome. OBJECTIVE: To perform a surgical outcome assessment by examining whether
the extent of ETSS approaches affected patient-specific sinonasal quality of life
as measured by the 22-item Sino-Nasal Outcome Test (SNOT-22). METHODS: A single
center prospective cohort study of patients operated on by the same skull base
team between 2012 and 2016. Patients with completed pre- and postoperative SNOT
22 were included. The primary outcome was SNOT-22 scores at preoperative, 0-1
month, 2-4 months, >5 months follow-up. Age, sex, tumor pathology, surgical
procedure, and intraoperative cerebral spinal fluid leak repair were also
obtained. RESULTS: Of the 249 ETSS performed, 148 patients (59%) had at least one
completed SNOT-22; 45 (18%) met the inclusion criteria. Sinonasal quality of life
based on SNOT-22 at the 0-1-month follow-up was significantly worse than the
presurgical levels (p < 0.05). However, there was a return of SNOT-22 scores to
preoperative levels at 2-4 months (p > 0.05), which was sustained at >5 months (p
> 0.05). Factors such as the extent of ETSS, a previous nasal surgery, repair of
an intraoperative cerebral spinal fluid leak, and the tumor pathology did not
affect SNOT-22 scores at any follow-up intervals (p > 0.05). CONCLUSION:
Sinonasal quality of life worsened after ETSS at 0-1 month follow-up but returned
to preoperative levels at 2-4 months and remained at postoperative levels >5
months. Analysis of these data will allow us to educate our patients that the
anticipated nasal morbidity after ETSS is usually only transient and should be
expected to recover to preoperative levels.
PMID- 29336292
TI - Use of intraoperative negative margins reduces inverted papilloma recurrence.
AB - BACKGROUND: Recurrence of inverted papilloma (IP) is a problem in 12-17% of
tumors. Controversy exists regarding benefits of intraoperative frozen section
histopathology (IFSH) for IP resection; however, to our knowledge, no study has
specifically investigated this. IFSH for IP resection is the standard of care in
our practice. We, therefore, reviewed our outcomes of using IFSH for IP
resection. A secondary goal was to assess the reliability of IFSH. METHODS:
Patients with IP who underwent surgical resection (2010-2016) with minimum 9
month follow-up were included. RESULTS: Twenty-two adults with IP met inclusion
criteria. All underwent surgery via endoscopic techniques, supplemented by
external ports in five patients. At the time of presentation, 36% IPs were
recurrent tumors; 68% were graded as Krouse stage 3. Resection was conducted
until "clear" (negative) mucosal margins were achieved on IFSH. In 6 (27%), a
"positive" IFSH result dictated additional resection to clear margins. Final
negative margins were achieved in all the patients. Both positive and negative
predictive values for IFSH were 100% (concordance with final pathology results).
Surveillance was performed every 1-6 months with nasal endoscopy by using imaging
when necessary. No recurrences were noted (0%) at mean follow-up of 40 months
(range, 10-73 months). CONCLUSIONS: Positive IFSH results led to increased
resection in 27% of the patients, with a 0% recurrence rate in this cohort. The
reliability of IFSH for IP is very high. No recurrence of IP was noted in any
patient at a mean follow-up of 3.3 years. IFSH may help reduce recurrence rates
of IP, but additional studies with longer follow-up are warranted.
PMID- 29336293
TI - Using the nasoseptal flap for reconstruction after endoscopic debridement of
radionecrosis in nasopharyngeal carcinoma.
AB - BACKGROUND: Radionecrosis is a complication of nasopharyngeal carcinoma (NPC)
that is difficult to treat. Endoscopic debridement is the first-line treatment
for radionecrosis. After debridement, however, either bone or the internal
carotid artery is exposed and requires mucosal coverage. OBJECTIVES: This study
sought to demonstrate the effectiveness of a nasoseptal flap (NSF) after
endoscopic debridement of radionecrosis in the reconstruction of nasopharyngeal
or skull base defects. METHODS: Nine patients with NPC who underwent navigation
guided endoscopic debridement, followed by NSF reconstruction between April 2013
and July 2016, were included. The patients' clinical features and outcomes were
evaluated. RESULTS: All nine patients had headaches, and eight had a foul odor
associated with their radionecrosis. One patient underwent three radiotherapy
treatments, four had two treatments, and the remaining four had just one
treatment. The foul odor disappeared after treatment in all the patients who had
been affected. The headache was significantly reduced after treatment in all
patients. The NSF detached in two patients. In one patient, NSF failed, and the
patient experienced postoperative rupture of the internal carotid artery. In the
seven other patients, the NSF successfully covered the resultant defects, despite
one intraoperative internal carotid artery rupture. Only two patients required
further debridement, whereas the others experienced complete healing after just
one surgical procedure. The nasopharyngeal surface was healthy-appearing in eight
patients (median follow-up, median 11 months). CONCLUSION: Reconstruction by
using NSF after endoscopic debridement for radionecrosis of NPC allowed for
faster healing and reduced the need for further debridement.
PMID- 29336294
TI - Esthetic nasolabial angle according to the degree of upper lip protrusion in an
Asian population.
AB - BACKGROUND: The positioning of the nasal tip is as esthetically important as the
tip projection when rhinoplasty is being considered. It is not uncommon for
Asians to have a protruding upper lip and teeth that affect the nasolabial angle
(NLA). This study aimed to find the preferred NLA according to the degree of
upper lip protrusion in an Asian population. METHODS: A left-side lateral
photograph of each participant was used for simulation of six different tip
angles by using a photoshop program. First, the angles of the upper lip
protrusion were changed into 10, 20, and 30 degrees by a perpendicular line to
the Frankfort line in each image; then, the NLAs were changed into six different
angles (from 75 to 110 degrees ) for each of the three angles of upper lip
protrusion for each model. Newly transformed images of nasal tips, six for the
male model and six for the female model, were made by using presentation software
slides and were placed in a random order. Then, 120 Korean raters were asked to
choose the most preferred image from among the slides. RESULTS: In 10 degrees of
upper lip protrusion, the preferred mean +/- standard deviation (SD) NLAs for the
male and female models were 88.7 +/- 6.4 degrees and 92.9 +/- 6.9 degrees ,
respectively. In 20 degrees of upper lip protrusion, the preferred mean +/- SD
NLAs for the male and female models were 80.9 +/- 6.9 degrees and 83.9 +/- 5.7
degrees , respectively. In 30 degrees of upper lip protrusion, the preferred
mean +/- SD NLAs for the male and female models were 78.4 +/- 5.5 degrees and
79.0 +/- 5.4 degrees , respectively. CONCLUSION: In an Asian population, the
preferred NLA was changed to a more acute angle according to the degree of upper
lip protrusion.
PMID- 29336295
TI - Transnasal endoscopic resection of pediatric orbital cyst: "How I do it".
AB - BACKGROUND: An orbital cystic lesion is a common orbital disease and has
classically been approached via external incision. The introduction of endoscopic
surgery has revolutionized the management of sinus and skull base disorders.
Similarly, endoscopic techniques have been increasingly used to access
intraorbital lesions with excellent outcomes, especially in pediatric patients.
OBJECTIVE: We described, in detail, the surgical technique of the endoscopic
approach to treat a pediatric orbital cyst. RESULTS: The cyst was completely
resected, and the patient quickly recovered without any complication. CONCLUSION:
The transnasal endoscopic surgical approach can be safe and effective for
pediatric patients with orbital lesions. Use of this approach is based on the
surgeon's experience and progressive instrumentation.
PMID- 29336296
TI - Superior turbinate eosinophilia correlates with olfactory deficit in chronic
rhinosinusitis patients.
PMID- 29336298
TI - [Diagnosis of vaginal discharge].
AB - Changes in vaginal discharge are often caused by imbalance in the vaginal
microflora, and laboratory testing is usually of little use, as most microbes
detected are commensals. In-office diagnosis in general practice using wet mount
microscopy and Amsel criteria is helpful and often sufficient to ensure correct
diagnosis and treatment. Laboratory testing of vaginal discharge should only be
performed, if sexually transmitted disease is suspected, if there is treatment
failure or inconclusive wet mount prior to gynaecological surgery, and in
pregnant women with recurrent miscarriage or preterm birth.
PMID- 29336297
TI - Add-on perampanel and aggressive behaviour in severe drug-resistant focal
epilepsies.
AB - This study aimed to investigate the incidence of aggressiveness in patients with
severe drug-refractory focal epilepsy (DRE) who started perampanel (PER) as add
on treatment, and to identify possible predisposing factors. Data on 49
consecutive patients with severe DRE who initiated PER were retrospectively
collected. Twelve of the 49 patients experienced aggressiveness as adverse event
related to PER treatment, one third of them on low (2-4 mg/day) PER dosages. PER
was discontinued in 10/12 patients because of aggressive behaviors.
Aggressiveness could appear after several months or even more than one year of
PER treatment. One third of patients with PER-related aggressiveness had
intellectual disabilities and 5/12 patients took levetiracetam as a concomitant
antiepileptic drug. Our study suggests that the occurrence of aggressive
behaviors in patients with severe DRE is not uncommon during PER treatment and
that it may occur after months or even years of treatment with a stable dosage,
requiring PER discontinuation in the great majority of patients.
PMID- 29336299
TI - [Duplication cyst as cause of ileus in a 16-year-old girl].
AB - A 16-year-old girl was admitted to hospital with lower abdominal pain. An
ultrasound examination suggested an ovarian cyst. A laparoscopic procedure found
that a duplication cyst in the patient's ileum had caused mechanical ileus. The
cyst was surgically resected through the creation of an end-to-end anastomosis,
and pathological examination confirmed it to be a duplication cyst. Duplication
cysts are a rare congenital disorder, especially past infancy. They are
characterized by an epithelium of gastrointestinal origin and a lining of smooth
muscle in their walls. The treatment is surgical resection when possible.
PMID- 29336300
TI - [Successful treatment of acute promyelocytic leukaemia without chemotherapy and
blood transfusion].
AB - Untreated acute promyelocytic leukaemia (APL) is a rapidly lethal blood cancer.
Conventional treatment consists of all-trans retinoic acid and chemotherapy.
Standard chemo-therapy-containing treatments necessitate the use of blood
products. This is a case report of typical APL in a 32-year-old female patient,
who due to religious conviction refused supportive therapy with blood products. A
treatment regimen consisting of all-trans retinoic acid and arsenic trioxide was
successful without the use of blood transfusions.
PMID- 29336301
TI - [Acute promyelocytic leukaemia].
AB - Acute promyelocytic leukaemia has changed from being a highly fatal to a highly
curable disease. Over time, key discoveries have identified the genetic and
molecular abnormalities, which cause the disease. First choice of treatment has
now changed from all-trans retinoic acid (ATRA) and chemotherapy to a chemo-free
combination of arsenic trixoide and ATRA. This new regimen has shown equal
responses and overall cure rates compared with the previous standard of care
containing conventional chemotherapy, but with much lower toxicity. This will
pave the way for better and easier treatment for elderly and frail patients.
PMID- 29336302
TI - [Cyclizine is sold in Denmark as an over-the-counter drug and has serious side
effects when overdosed].
AB - Cyclizine is sold in Denmark as an over-the-counter drug and affects not only
histaminergic but also muscarinergic, serotonergic and alpha-adrenergic
receptors, with side effects such as respiratory depression and cardiac
arrhythmias, leading to fatalities. Due to the numerous side effects, it raises
questions concerning the status of cyclizine as an over-the-counter drug. Data of
healthcare contacts because of cyclizine intoxication in the 2014-2016 period
should be analyzed to further illuminate the health risk of cyclizine poisoning.
PMID- 29336304
TI - Why do women with melanoma do better than men?
AB - Harnessing female sex hormones may improve how all patients with melanoma respond
to treatment.
PMID- 29336303
TI - Keratinocytes mediate innocuous and noxious touch via ATP-P2X4 signaling.
AB - The first point of our body's contact with tactile stimuli (innocuous and
noxious) is the epidermis, the outermost layer of skin that is largely composed
of keratinocytes. Here, we sought to define the role that keratinocytes play in
touch sensation in vivo and ex vivo. We show that optogenetic inhibition of
keratinocytes decreases behavioral and cellular mechanosensitivity. These
processes are inherently mediated by ATP signaling, as demonstrated by
complementary cutaneous ATP release and degradation experiments. Specific
deletion of P2X4 receptors in sensory neurons markedly decreases behavioral and
primary afferent mechanical sensitivity, thus positioning keratinocyte-released
ATP to sensory neuron P2X4 signaling as a critical component of baseline
mammalian tactile sensation. These experiments lay a vital foundation for
subsequent studies into the dysfunctional signaling that occurs in cutaneous pain
and itch disorders, and ultimately, the development of novel topical therapeutics
for these conditions.
PMID- 29336305
TI - Inferring joint sequence-structural determinants of protein functional
specificity.
AB - Residues responsible for allostery, cooperativity, and other subtle but
functionally important interactions remain difficult to detect. To aid such
detection, we employ statistical inference based on the assumption that residues
distinguishing a protein subgroup from evolutionarily divergent subgroups often
constitute an interacting functional network. We identify such networks with the
aid of two measures of statistical significance. One measure aids identification
of divergent subgroups based on distinguishing residue patterns. For each
subgroup, a second measure identifies structural interactions involving pattern
residues. Such interactions are derived either from atomic coordinates or from
Direct Coupling Analysis scores, used as surrogates for structural distances.
Applying this approach to N-acetyltransferases, P-loop GTPases, RNA helicases,
synaptojanin-superfamily phosphatases and nucleases, and thymine/uracil DNA
glycosylases yielded results congruent with biochemical understanding of these
proteins, and also revealed striking sequence-structural features overlooked by
other methods. These and similar analyses can aid the design of drugs targeting
allosteric sites.
PMID- 29336308
TI - Clinical significance of concordance or discordance between fractional flow
reserve and coronary flow reserve for coronary physiological indices,
microvascular resistance, and prognosis after elective percutaneous coronary
intervention.
AB - AIMS: We aimed to investigate the impact of concordance or discordance of
fractional flow reserve (FFR) and coronary flow reserve (CFR) on coronary flow
profiles and microvascular resistance after percutaneous coronary intervention
(PCI), and the prognostic impact of the periprocedural physiological indices.
METHODS AND RESULTS: A total of 249 de novo physiologically significant coronary
lesions from 231 patients who underwent FFR, CFR, and index of microcirculatory
resistance (IMR) examinations before and after PCI were included. Baseline
characteristics and physiological indices were compared between the concordant
(FFR <=0.80 and CFR <2.0, n=114) and discordant (FFR <=0.80 and CFR >=2.0, n=135)
groups. Follow-up data were collected to determine predictors of cardiac events.
Shortening of the mean transit time, CFR improvement, and decrease in the
hyperaemic IMR were all significantly greater in the concordant territories. Cox
proportional hazards analysis showed that a lower pre-PCI CFR was an independent
predictor of adverse events at a median follow-up of 26.5 months, whereas neither
the pre- nor post-PCI FFR was predictive of events. Event-free survival was
significantly worse in patients with a lower pre-PCI CFR. CONCLUSIONS: FFR/CFR
concordantly abnormal territories provide a favourable benefit as assessed by
coronary physiological indices after elective PCI. The pre-PCI CFR may predict
adverse cardiac events.
PMID- 29336309
TI - Dedicated bifurcated balloon for coronary bifurcation lesions: a preclinical
proof of concept.
PMID- 29336307
TI - Activation of G protein-coupled estrogen receptor signaling inhibits melanoma and
improves response to immune checkpoint blockade.
AB - Female sex and history of prior pregnancies are associated with favorable
melanoma outcomes. Here, we show that much of the melanoma protective effect
likely results from estrogen signaling through the G protein-coupled estrogen
receptor (GPER) on melanocytes. Selective GPER activation in primary melanocytes
and melanoma cells induced long-term changes that maintained a more
differentiated cell state as defined by increased expression of well-established
melanocyte differentiation antigens, increased pigment production, decreased
proliferative capacity, and decreased expression of the oncodriver and stem cell
marker c-Myc. GPER signaling also rendered melanoma cells more vulnerable to
immunotherapy. Systemically delivered GPER agonist was well tolerated, and
cooperated with immune checkpoint blockade in melanoma-bearing mice to
dramatically extend survival, with up to half of mice clearing their tumor.
Complete responses were associated with immune memory that protected against
tumor rechallenge. GPER may be a useful, pharmacologically accessible target for
melanoma.
PMID- 29336306
TI - MERS-CoV spillover at the camel-human interface.
AB - Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus from
camels causing significant mortality and morbidity in humans in the Arabian
Peninsula. The epidemiology of the virus remains poorly understood, and while
case-based and seroepidemiological studies have been employed extensively
throughout the epidemic, viral sequence data have not been utilised to their full
potential. Here, we use existing MERS-CoV sequence data to explore its
phylodynamics in two of its known major hosts, humans and camels. We employ
structured coalescent models to show that long-term MERS-CoV evolution occurs
exclusively in camels, whereas humans act as a transient, and ultimately terminal
host. By analysing the distribution of human outbreak cluster sizes and zoonotic
introduction times, we show that human outbreaks in the Arabian peninsula are
driven by seasonally varying zoonotic transfer of viruses from camels. Without
heretofore unseen evolution of host tropism, MERS-CoV is unlikely to become
endemic in humans.
PMID- 29336310
TI - Two-year outcomes of high bleeding risk patients with acute coronary syndrome
after Biolimus A9 polymer-free drug-coated stents: a LEADERS FREE substudy.
PMID- 29336311
TI - Comparison of the effects of P2Y12 receptor antagonists on platelet function and
clinical outcomes in patients undergoing Primary PCI: A substudy of the HEAT-PPCI
trial.
AB - AIMS: The HEAT-PPCI trial compared bivalirudin and unfractionated heparin in
patients undergoing primary percutaneous coronary intervention (PPCI). The aim of
this study was to report pre-specified, secondary analyses comparing the effects
of P2Y12 inhibiting agents on platelet reactivity and clinical events. METHODS
AND RESULTS: All patients received preprocedural oral antiplatelet therapy.
During the early stages of the trial, the P2Y12 inhibitor of choice was prasugrel
with some use of clopidogrel. Later, routine therapy switched to ticagrelor. For
cases performed during working hours, multiple electrode aggregometry (MEA) was
used to assess ADP-induced platelet aggregation at the end of the index
procedure. The effect of P2Y12 inhibitors on the primary efficacy (major adverse
cardiac events [MACE]) and safety (major bleeding) outcomes was assessed in all
patients. Multiple logistic regression was used to adjust for differences in
baseline characteristics. With MEA data from 469 patients, prasugrel therapy
resulted in significantly greater suppression of ADP-induced platelet aggregation
at 40 U (23, 78) (median; interquartile range [IQR]) when compared against
ticagrelor 75 U (41, 100.75); p<0.001 or clopidogrel 79 U (56, 96); p<0.001. In
the entire study population (N=1,803), prasugrel therapy was associated with
significantly fewer MACE (26/497; 5.2%) in comparison to ticagrelor (83/1,123;
7.4%) or clopidogrel (18/183; 9.8%); odds ratio (OR) 0.64, confidence interval
(CI): 0.41-0.99, p=0.045. For major bleeding, there were no significant
differences among the three groups - clopidogrel (3/183; 1.6%), prasugrel
(13/497; 2.6%) and ticagrelor (43/1,123; 3.8%); OR 0.73, CI: 0.39-1.35, p=0.31.
Patients treated with clopidogrel had more high-risk features and clopidogrel use
was more common as an alternative to prasugrel. After adjustment, there were no
significant differences in the rates of MACE (OR 0.70, CI: 0.41-1.21, p=0.20) or
major bleeding (OR 0.80, CI: 0.41-1.60, p=0.53). CONCLUSIONS: In HEAT-PPCI,
patients who received prasugrel (rather than clopidogrel or ticagrelor) had
significantly greater suppression of ADP-induced platelet aggregation at the end
of the procedure. After adjustment for differences in baseline characteristics,
there were no significant differences in ischaemic or bleeding outcomes among the
antiplatelet therapies.
PMID- 29336312
TI - Apocrine mixed tumour on the abdomen: an atypical location.
PMID- 29336313
TI - Reduced IgG anti-desmocollin autoantibody titre and concomitant improvement in a
patient with pemphigus vegetans.
PMID- 29336314
TI - Two cases of annular acute generalized exanthematous pustulosis induced by
terbinafine.
PMID- 29336316
TI - Mycosis fungoides in patients with psoriasis: an ongoing issue.
PMID- 29336315
TI - A high neutrophil to lymphocyte ratio prior to BRAF inhibitor treatment is a
predictor of poor progression-free survival in patients with metastatic melanoma.
AB - Some studies have shown that a high neutrophil/lymphocyte ratio (NLR) >=4 before
initiating ipilimumab treatment is an independent prognostic indicator of poor
survival in patients with metastatic melanoma (MM). To determine whether the NLR
before starting BRAF inhibitor (BRAFi) treatment in patients with (MM) is
associated with progression-free survival (PFS). This retrospective study
included 49 patients consecutively receiving BRAFi for MM between July 2012 and
December 2014. Cox proportional hazards regression was used to analyse the
relationship between NLR and other factors, such as lactate dehydrogenase (LDH),
performance status, BRAFi as first- or second-line therapy, and corticosteroid
intake with PFS. The NLR before starting BRAFi was significantly associated with
PFS based on univariate analysis and multivariate analysis adjusted for potential
confounding factors, such as LDH activity, ulceration, performance status, first
line therapy, and corticosteroid intake. A high NLR (continuous variable) was
associated with short PFS (HR: 1.35; 95% CI: 1.07-1.70; p = 0.01), and NLR >=4
was associated with shorter PFS (HR: 3.24; 95% CI: 1.30-8.12; p = 0.01).
Corticosteroid intake was not associated with short PFS based on multivariate
analysis. An NLR >4, before starting BRAFi treatment, is an independent
prognostic indicator of poor progression-free survival.
PMID- 29336317
TI - Association between Helicobacter pylori infection and vulvar lichen sclerosus: a
clinical comparative study.
PMID- 29336318
TI - Nevus anelasticus in a school-aged girl: ultrastructural observation and Er:YAG
laser treatment.
PMID- 29336319
TI - Acute renal injury induced by oral valacyclovir.
PMID- 29336320
TI - Two childhood cases of pigmented dermatofibrosarcoma protuberans with atrophic
change.
PMID- 29336321
TI - Epstein Barr virus and invasive mammary carcinomas: EBNA, EBERs and molecular
profile in a population of West Algeria.
AB - Breast cancer is the common malignancy that affects women worldwide, but
conventional risk factors account for only a small proportion of these cases. A
possible viral etiology for breast cancer has been proposed and Epstein-Barr
virus (EBV) is a widely studied candidate virus. The objective of this study is
to determine the association of EBV infection with infiltrating ductal carcinomas
(IDC). This descriptive study was carried out in the laboratory of developmental
biology and differentiation, from 2012 to 2014. Of 39 cases, we determined the
clinicopathological characteristics of the population. Of the 23 cases of IDC, we
implemented the techniques Elisa, immunohistochemistry and in situ hybridization.
To determine the serological profile, overexpression of onco-proteins EBNA-1,
HER2, the mitotic index Ki67 and detection of the presence of the viral genome.
The mean age is 57.40+/-4, SBR II predominates with 70%, pN+ (27%), RE+ (58%),
RP+ (52%), HER2 (81%), Luminal A (34%), Luminal B (14%), HER2 (24%), and triple
negative (28%). The serological profile of IgG VCA + in IgG EBNA-1 (87%), EBNA-1
P79 (82%) with a positive relationship between the IgG EBNA-1 and EBNA-1 P79
serology profile (p=0.001), HER2 (p=0.003) and with the molecular profile
(p=0.051), EBNA-1 overexpression in (13%). The viral genome (EBER) is found in
the tumors 43% representing an inverse relationship with the overexpression of
Ki67 and a positive relationship with the overexpression of HER2. In our study we
found an association with the presence of the EBV virus and the IDC studied.
PMID- 29336322
TI - Treatment of nail psoriasis with topical application of clobetasol propionate
0.05% solution: a pilot study.
PMID- 29336323
TI - Nivolumab for recurrent cutaneous squamous cell carcinoma: three cases.
AB - Programmed cell death ligand 1 (PD-L1) is frequently expressed in cutaneous
squamous cell cancer (CSCC) and preliminary data from an ongoing clinical trial
suggest that programmed death receptor 1 (PD-1) checkpoint inhibitors may be
useful to treat patients with metastatic non-melanoma skin cancer. To report a
series of three patients with advanced CSCC treated with nivolumab, showing that
commercially available PD-1 checkpoint inhibitors may be useful in non-melanoma
skin cancer patients without access to a clinical trial. All patients had
previous chemotherapy. All cancers were PD-1 ligand (PD-L1)-positive based on
immunohistochemistry. Patients consented to off-label therapy with nivolumab,
which is commercially available in Switzerland. Two patients had a partial tumour
response, and have been receiving therapy for more than 12 months. One patient
had stable disease after three months, and therapy is also ongoing. So far, no
severe adverse effects have occurred. Our cases confirm previous reports
demonstrating a clinical effect and tolerability of PD-1 checkpoint inhibitors
for heavily pre-treated patients with metastatic CSCC. Commercially available PD
1 checkpoint inhibitors may be useful in these patients who should be considered
for PD-1 checkpoint inhibitor therapy, preferentially within clinical trials.
PMID- 29336324
TI - Diagnostic value of autoantibody titres in patients with bullous pemphigoid.
AB - BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering
disease of the skin requiring skin and serum tests for a precise diagnosis.
OBJECTIVES: We analysed the sensitivity and specificity of BP-relevant parameters
and the value of autoantibody titres during follow-up of BP patients. MATERIALS &
METHODS: In a retrospective single-centre study, we included 200 consecutive
patients with BP and 400 non-BP patients, and evaluated the test results of
patients' serum and skin. In addition, we followed patients' autoantibody titres
and clinical characteristics. RESULTS: BP180-ELISA revealed the highest
sensitivity (85.0%; specificity: 93.9%), while BP230-ELISA demonstrated the
lowest sensitivity (55.5%; specificity: 92.9%). Direct and indirect
immunofluorescence showed comparable results for sensitivity (77.2%/72.7%) and
specificity (94.9%/93.7%). The sensitivity for skin histology was 76.3%
(specificity: 81.3%). Longitudinal analysis showed significant changes in
autoantibody titres. CONCLUSIONS: BP diagnostics should include serum tests for
BP autoantibodies and skin immunofluorescence. Skin histology is supportive for
diagnosis. Autoantibody titres are markers for disease activity.
PMID- 29336325
TI - [Surgical and academic education in Urology.]
PMID- 29336326
TI - [Current status of Urological Education in Spain.]
AB - INTRODUCTION: Urology is a medicalsurgical specialty that deals with the study,
diagnosis and treatment of medical and surgical conditions of the urinary tract
and retroperitoneum in both sexes and of the male genital tract without age
limit. The traditional method of training is based on the imitation of the skills
and behaviors of the tutors, creating variability in the training between
different centers and giving a passive role to resident internal physicians
(MIR). LEGISLATIVE FRAMEWORK: The 2006 BOE establishes the specific formative
content in its theoretical, practical and scientific facets. At the beginning of
the MIR training period, the first year focuses on general surgical training and
the remaining four on specific urological training. The current legislative
framework that regulates our specialty is one of the oldest, with no prospect of
renewal, since this would be carried out with the development of the trunk
project, currently paralyzed after the judgment of the Supreme Court. Therefore,
we are in a situation of uncertainty with a legal framework in renewal plans.
CURRENT STATE OF TRAINING: a National survey shows the degree of surgical
participation of the MIR is low, as well as training on models and course
attendance. In addition, the self-confidence they feel for interventions that
could be considered of low complexity is high, for activities such as
consultation is moderate and for interventions of moderate-high complexity is
low. CONCLUSION: The current training program is upgradeable. New studies and
efforts should aim to standardize the acquisition of surgical and non-surgical
skills, guarantee access to surgical training courses, establish a minimum of
required interventions per year and at the end of residency, foster academic
training, participation in research of residents and achieve an objective
assessment of the specialty.
PMID- 29336327
TI - Current status of urological training in Europe.
AB - Modern urological training has changed drastically in the past years, due to the
global surgical training trends, advances in technology, subspecialization of the
field and, working hour regulations for doctors. The lack of a standardized
curriculum across Europe, puts in evidence the great difference in the
requirements in every country, from the start of the residency, to obtaining the
accreditation. We sought to identify problems related to medical, scientific and
surgical activity during urological training, and summarize data obtained from
surveys realized during the European Urology Residents Education Programme
(EUREP) in 2013, and from countries such as Germany, Italy and Spain. Data from
surveys reveals an evident lack of surgical confidence across all participants
for major procedures, a general non-compliance with the working hour regulations,
and a worrisome risk for burnout and negative consequences in resident's personal
lives. Possible solutions are discussed, involving an early preference for a
particular practice, and a standardized simulation-based training. The European
Association of Urology (EAU) and the European School of Urology (ESU) offer a
wide range of working groups, educational and scientific activities for improving
the acquisition of competencies (surgical and scientific) of residents and
urologists at any point of their career. We describe a brief description of the
most important EAU and ESU opportunities.
PMID- 29336328
TI - Needs, realities and expectations for urology training: Questionaire-based study.
AB - OBJECTIVE: Urology residency training is a difficult and complex education period
for urology residents. This education period differs in countries and mainly for
5 years. In this study, we aimed to assess the expectations and the realities for
Turkish urology residents and to evaluate the adequacy of their education in the
field of urology. METHODS: In this study, 113 Turkish urology residents have been
included and residents were asked 24 questions related with their surgical
skills, thoughts towards their educations, their future plans and including
demographic information. RESULTS: The years of residency were divided as; 1st
year-12 (10.6%), 2nd year-17 (15%), 3rd year-22 (19.4%), 4th year-24 (21.3%) and
5th year-38 (33.7%). Mainly they suffered from the lack of practical education
and the lack of encouragement to scientific and academic works, studies.
CONCLUSION: Urological education must be standardized and must cover the
educational needs of urology residents.
PMID- 29336329
TI - [Current status of urological training in Latin America.]
AB - OBJECTIVE: Achieving residents' medical training of quality is a constant concern
in the Confederacion Americana de Urologia (CAU), the third Urological Society
worldwide. We aim to analyze the diversity of state training programs, with the
intention to identify opportunities for global improvement within them and also
to analyse the professional reality in different countries. METHODS: Data from
2nd and 3rd Foro Educativo CAU regarding postgraduate training and labour
implications are reviewed. This information is complemented by the opinion of
representatives involved with the academic training in Confederacion Americana de
Urologia, who have analyzed the reality and current status of the urological
training through a 10-question survey that describes different aspects of
residency program in the countries confederated in CAU. RESULTS: A total of 3,000
graduate doctors train as residents in Urology at the CAU environment. Each year
670 residents begin their training program in Latin America, Spain and Portugal,
a territory that serves nearly 650 million people, with an active professional
force of around 16.800 professionals. Detailed data on training, employment and
supporting reality in the countries that comprise the CAU are presented. We also
discuss the proportion of residents who carry out research and doctorate during
the residency program. Finally, we examine the proportion of professionals who
receive specific training at the end of their residence, the relative importance
of this training and what are the most popular environments to carry it out.
CONCLUSIONS: Current postgraduate training in CAU environment is heterogeneous in
their programs, as well as in the modes of accreditation and recertification.
Academic activities do not seem to be properly valued. However, specific training
offers better expectations of professional development.
PMID- 29336330
TI - [The current urological training program in Spain. Urology National Specialty
Commission.]
AB - OBJECTIVES: 44/2003 Law involved the creation of the National Council of
Specialties in Health Sciences and the National Commissions of the Specialties in
Health Sciences. METHODS: Analysis of the main laws implicated in Specialized
Training and the role of the National Specialty Commission. DISCUSSION: 44/2003
Law regulates the training of health professionals and establishes the procedure
for the training programs creation by the National Specialty Commission and its
later approval and publication in the BOE. Access to specialized training will be
carried out with the annual and national MIR exam. The Health Ministry
establishes the criteria for educational centers accreditation, and the National
Specialty Commission issues a favorable or unfavorable report as advisor about
new accreditation requests. 183/2008 RD develops the tutor figure, the formative
evaluation through the Resident's Book and how will be like the external
rotations. CONCLUSIONS: to understand the Urology's specialty training system we
must know the laws that regulate it, being the most important the 44/2003 Law.
The National Specialty Commission is an advisory party of the Ministry, whose
main function is to elaborate the Urology training program and to establish the
evaluation criteria of the specialists in formation.
PMID- 29336331
TI - [Job status after the resident training period in Spain. Analysis of a national
survey.]
AB - OBJECTIVES: Since the establishment of specialization of medicine through the
residency system, Spanish health care has sought to maintain a balance between
established needs and trained professionals, with the aim of avoiding the deficit
or excess of health specialists with its consequences. The objective of the
present review is to know the working conditions of urologist specialists at the
end of the residency training period. METHODS: The results of a survey for
urologist who completed their residency contract from 2012 to 2016 are presented,
assessing working status, academic and working data during the first months after
the completion of specialized training. RESULTS: A total of 42 surveys were
collected. All respondents had a working contract within 6 months of completing
their training. 71% had a temporary contract, most with duration of less than one
year. There are more contract numbers in the public health system, although they
increase progressively in the private sector. More than half of the respondents
were satisfied with their work situation. CONCLUSIONS: The work insertion of the
recently specialized urologists is high, reaching 100% within 6 months of
finishing their specialization. Labor quality issues are not so positive,
observing great working instability associated to a high proportion of temporary
contracts lower than 6 months.
PMID- 29336332
TI - [Fatigue syndrome: Stress, Burnout and depression in Urology.]
AB - OBJECTIVE: To determine the factors related to stress, Burnout and depression in
urology, as well as consequences in residents and urologists, in addition to the
possible applicable strategies to diminish and treat them. ACQUISITION OF THE
EVIDENCE: Depression, stress and Burnout syndrome has become a problem in urology
specialty. These topics have gained interest in international congresses and
urological associations. Efforts are being made to find related factors as well
as possible strategies and applicable support programs. SYNTHESIS OF EVIDENCE:
Burnout frequency is higher among health professionals than general population,
40-76% in students and residents, its incidence has skyrocketed in recent years,
in addition Urology is one of the specialties with highest incidence and
severity. Its increase has been related to work overload, documentation,
administrative/bureaucratic workload, hostile work environment; its consequences
include poor work performance, medical errors, depression, substance abuse,
disruption in family and couple relationships and suicidal ideation. Strategies
for prevention including resilience training, lifestyle balance, teamwork, and
support programs. CONCLUSION: Stress, burnout and depression are problems in
urology, early detection, promoting individual techniques in resilience,
lifestyle and teamwork are fundamental now and for the future of the specialty.
Developing and implementing support programs should be seriously considered by
health systems and urological associations.
PMID- 29336333
TI - Simulation and training in Urology - in collaboration with ESU/ESUT.
AB - Being a Surgeon today means taking on your shoulders countless responsibilities.
It is definitely a high-stakes job but, even though the professionals do not go
through the intense, focused and demanding training schedule as followed by the
other equally risky fields, it doesn't yet require any practical training
certification. Simulation was introduced in the aviation field in the early '30s
with the "Link Trainer", designed to reproduce the most difficult flying case
scenario: landing on an air-carrier. After almost a century, flight simulation is
still becoming more sophisticated, while surgical training is slowly starting to
fill the gap. The aim of a simulator is to produce an "imitation of the operation
of a real-world process or system over time". This short but effective definition
explains why simulators are utilised across different fields. There is no doubt
that surgeons are continuously undergoing a condition of stress, even in
nonthreatening situations, while performing a procedure. This condition adds a
relevant variable to surgery, meaning that mastering technical skills is not
always equal to "safe surgery". This is why "non-technical skills" (NTS) training
should be a part of any simulation based training opportunity and will probably
start to be always more part of the Handson Training programs.
PMID- 29336334
TI - [Training in basic and advanced laparoscopy: Evaluation of a 30-year experience
in a training program in Spain.]
AB - The lack of globally established standards for learning urological laparoscopy
has not prevented laparoscopic techniques from evolution and continuous
development. Laparoscopy coexists with robotic surgery today, and in the last
decade there have been many techniques that have undergone a boom with the use of
a laparoscopic approach (total and partial nephrectomy, pyeloplasty,
colposacropexy, etc.).We intend to evaluate the progressive incorporation of
different surgical techniques in the laparoscopic learning program and, on the
other hand, to analyze the evolution of training programs in urological
laparoscopy to bring this type of techniques within the hospital surgical
activity. We describe our 30-years experience in different training programs in
urological laparoscopy that have been sponsored by the Spanish Association of
Urology (AEU), and have undergone several validity studies to assess their
capacity in order to evaluate effectively basic and advanced laparoscopic skills.
We will also highlight the current and future trend towards training models based
on surgical competences where individualized training, accreditation and
specialization of tutors is crucial, and where the increase in the use of
training and evaluation methods based on the simulation are increasingly common.
PMID- 29336335
TI - [Evaluation of competencies in urology. Esscolap(r) basic, as aproximation to
urologists skills improvement.]
AB - : Urology needs models of competencies assessment, although there is a wide range
of tools not yet integrated into the official training programs. CONTEXT: At
present, there is no universal framework for measuring surgeons' level of
competence. Urology training programs should provide and consider knowledge,
pyschomotor/cognitive skills, and simulator, cadaver or animal models-based
training. Validity is a complex concept that refers to the capacity of the
evaluation tool, so it is necessary to demonstrate several types of validation to
assure the capacity of a method, reinforced with different reliability tests and
calculation of internal consistency between evaluators. OBJECTIVE: Based on a
structured dossier of surgical skills, classified by groups, the ESSCOLAP(r)
Basic system was proposed with 5 simulator tasks to evaluate basic laparoscopic
skills. Once validated in the JUMISC (Spain), the tool was proposed to extend its
scope and implementation in other locations. RESULTS: Our system has not yet
demonstrated a full validity in the real clinical setting because a predictive
validity needs to be demonstrated on the basis of clinical data. It also suffers
from a certain range of subjectivity, thus implying clear and defined criteria
for any situation. Factors like the number of evaluators and tasks to assess will
influence the reliability tests that measure the degree of agreement between
evaluators, so that a higher number of evaluated cases would imply a greater
reliability of our system. Finally, we assume that the incorporation of this type
of tools implies an added cost, charged to the public and private responsible
institutions, which will only be considered cost-effective when it is
demonstrated its real and positive traceability in health outcomes. CONCLUSIONS:
ESSCOLAP(r) Basic, of quick and simple implementation capacity, has been
validated and calibrated for the evaluation of basic technical skills in
laparoscopy.
PMID- 29336336
TI - [Training program in urological laparoscopic surgery. Future perspective.]
AB - Nowadays in urology, laparoscopic surgery is a reality that implies a very high
percentage of the daily surgical activity. The interest in laparoscopy in
urological pathology is undeniable, and the advantages for our patients with this
approach are clear in most cases. But how do we deal with learning curve of this
technique? What is the difficulty in laparoscopy training? What future
perspectives might offer this approach? Difficulties in learning laparoscopy are
easily identified and clear. The loss of the image in 3 dimensions, loss of
touch, great dependence on surgical instruments, among others. For all these
reasons, it seems common sense that the learning of laparoscopic surgery is
structured and organized in a progressive increase in the difficulty of the
exercises, which will seek to acquire the necessary skills before facing the
patient inside the operating room.
PMID- 29336337
TI - [Training program in endourological surgery. Future perspectives.]
AB - Current training in urological endoscopy lacks a specific training program.
However, there is a clear need for a specific and uniform program, which will
ensure the training, regardless of the unit where it is carried out. So, the goal
is to first evaluate the current model and then bring improvements for update.
The hospital training accreditation programme are only the adjustment of the
official program of the urology specialty to the specific circumstances of each
center, which causes variability in training of residents. After reviewing 19
training programs belonging to 12 Spanish regions. The current outlook shows that
scarcely 10% of hospitals quantify the number of procedures/ year, although the
Spanish program emphasizes that the achievement of the residents should be
quantified. Urology residents, sense their training as inadequate and therefore
their level of satisfaction is moderate. The three main problems detected by
residents as an obstacle on their training are: the lack of supervision, tutors
completing their own learning. Finally, the lack of quantification in surgical
activities is described as a threat. This has no easy solution, since the
learning curve of the most common techniques in endourology is not correctly
established. Regarding aspects that can improve the current model, they highlight
the need to design a specific program. The need to customize the training, the
ineludible accreditation of tutors and obviously dignify the tutor's teaching
activity. Another basic aspect is the inclusion of new technologies as training
tools, e-learning. As well as the implementation of an adequate competency
assessment plan and the possibility of relying on simulation systems. Finally,
they highlight the need to attend monographic meetings and external clinic
rotations to promote critical training.
PMID- 29336338
TI - Training in urological robotic surgery. Future perspectives.
AB - As robotics are becoming more integrated into the medical field, robotic training
is becoming more crucial in order to overcome the lack of experienced robotic
surgeons. However, there are several obstacles facing the development of robotic
training programs like the high cost of training and the increased operative time
during the initial period of the learning curve, which, in turn increase the
operative cost. Robotic-assisted laparoscopic prostatectomy is the most commonly
performed robotic surgery. Moreover, robotic surgery is becoming more popular
among urologic oncologists and pediatric urologists. The need for a standardized
and validated robotic training curriculum was growing along with the increased
number of urologic centers and institutes adopting the robotic technology.
Robotic training includes proctorship, mentorship or fellowship, telementoring,
simulators and video training. In this chapter, we are going to discuss the
different training methods, how to evaluate robotic skills, the available robotic
training curriculum, and the future perspectives.
PMID- 29336339
TI - [Training program in oncologic urology. Future prospectives.]
AB - Urology is a medical-surgical specialty that deals with the study, diagnosis and
treatment of the medical and surgical diseases of the urinary apparatus and
retroperitoneum in both sexes and the male genital apparatus without age limit,
due to congenital, traumatic, septic, metabolic, obstructive and oncological
conditions. Urologic oncology is the broadest urological part, where research and
new advances make continuous learning essential. In this chapter we treat all
academic features related with training in the field of Urooncology.
PMID- 29336340
TI - [Training program on medical urology: Future perspectives.]
AB - Urology is defined as the medical-surgical specialty that includes the study,
diagnosis and treatment of medical conditions of the urinary system. It is well
specified by the National Commission of Specialties that we must know the medical
pathology that concerns us. However, on occasions, resident training focuses on
the surgical field and oncological pathology, which, although one of the main
pillars of the specialty, is usually to the detriment of training in medical and
functional pathology. We conducted a survey of residents in the fourth year of
Urology in Spain, where we asked about the quality of training in Andrology and
Functional Urology. The average rotation time is 3.5 months in each unit. Only
20% consider that their training is satisfactory and sufficient in Andrology.
Seventy-five percent of residents surveyed believe that their training in
Functional Urology is acceptable or sufficient, both medical and surgical. There
are numerous fields of action to improve the training of residents and young
urologists in this country in the management of urological medical pathology. The
future is open, and it is in our hand to set up a training for urology residents
within excellence and to be recognized both nationally and internationally as one
of the great pillars of Spanish Urology. In this chapter we will analyze the
current situation in the training of Spanish Urology Residents in urological
medical pathology, and we will focus on training in functional urology and
andrology.
PMID- 29336341
TI - [Academic opportunities for Urology residents in Spain.]
AB - The development of an academic career gives a new dimension to the chosen
specialty. It consists in combining clinical activity with teaching and research
activity. In the area of surgical specialties there is currently a lack of
academic positions which is necessary to overcome to maintain the quality
standards. Residency and the immediate posterior period it is a good time to star
our academic career. This side of our specialty demands an additional effort,
great motivation, clear and determined objectives and especially dedication.
Considering Urology is a medical-surgical specialty it offers a perfect scenario
for the development of research activity. In this article we review some of the
available options to develop an academic career starting during residency. Among
them we find some indispensable if one wants to develop an universitary career
and others that facilitate the learning of scientific methodology, indispensable
to elaborate a research project.
PMID- 29336342
TI - [Homogeneity of the European training program. The role of the European Board of
Urology.]
AB - From its origins and acting through its specific committees, the E.B.U. has been
dedicated to the improvement and standardization of urological training across
Europe. Identifying minimal requirements for urology training, publishing a
European Curriculum and defining basic rules for accreditation of educational
activities, hence, offering a systematic assessment for the recognition of
quality. Working through different dedicated committees, the E.B.U. oversees
every aspect on the urological training in Europe. The Accreditation Committee
sets standards for the accreditation of educational/scientific activities and
ensures the proper evaluation of submissions for CME/ CPD accreditation. The
Certification Committee oversees the appropriate implementation of the EBU
Certification programme and ensures a thorough quality assessment process that
aims to standardise urological training across Europe. Finally, the Examination
Committee, that is structured into two sub-committees one for the In Service
Assessment (I.S.A.) and the written F.E.B.U. examination (Part 1) and a second
for the oral F.E.B.U. examination (Part 2). The committee works to ensure that
all EBU examinations and associated assessment activities are thoroughly prepared
and conducted in accordance with EBU's criteria.
PMID- 29336343
TI - [On line learning in urologic surgery. The value of the 2.0 Web tools.]
AB - The field of Surgery is under the pressure of accelerated change where
technological cycles get shorter and shorter, sometimes transformational.
Learning and training have gotten a key role because learning curves for new
techniques directly affect patient's safety and learning cycles are slower. The
traditional learning model within the urology department is overwhelmed. We need
new training and learning methods. The aim of this article is to perform a
critical analysis of the current status of learning in urological surgery and the
challenges we face, evaluating how new information and communication technologies
can help us to facilitate the learning process. We also present our initial
experience with on line education on upper urinary tract laparoscopic and robotic
surgery using the 2.0 Web tools.
PMID- 29336344
TI - [The urologist of the future and new technologies.]
AB - The last 25 years have brought about revolutionary changes for medicine and in
particular for urology: internet was only in its infancy, medical records were
written on paper, searches for medical information were done in the hospital
library, medical articles were photocopied and our relationship with patients
only existed face to face. Social networks had not yet appeared and even Google
did not exist. Just imagine what might happen during the next 25 years, we're
going to see even more radical changes. The urologist of the future is going to
see the arrival of artificial intelligence, collaborative medicine, telemedicine,
machine learning, the Internet of Things and personalized robotics; in the
meantime, social media will continue to transform the interaction between
physician and patient. The training of urologists will also be different thanks
to new learning technologies such as virtual reality or augmented reality. IBM
Watson Health through its system of artificial intelligence and its learning
algorithms will become our essential travel companion. The urologist of the
future, as well as physician, will have to acquire the necessary technological
skills in order to use all these new tools which are already on the horizon.
PMID- 29336345
TI - [The role of social media in academic training in Urology. Adequate use.]
AB - Social media is characterized because all its services are participative. Users
of 2.0 technologies can interact easily and openly with other people, share
resources and communicate immediately and simultaneously. Research improves from
participatory technologies by allowing groups to share reflections,
methodologies, resources and results.The social media platform with greater
diffusion and use in urology is possibly Twitter because it allows to realize
what is known like "microblogging", the users generate comments and brief
messages through the creation of "tweets". It is possible to determine that there
are three broad areas from a scientific point of view in which social media are
manifested: sharing research, resources and results. The use and applications of
social media become a major responsibility in the area of health and urology,
obviously for reasons of privacy, scientific rigor, ethics and the nature of the
medical - legal content.
PMID- 29336346
TI - Future of Urology training.
AB - Urology has become more complex through the years, as it comprises increasingly
sophisticated medical and surgical technologies such as advanced medical tumour
therapies, and endourological, laparoscopicand robotic surgical techniques.
Training in urology starts during medical school and once a medical student
chooses to specialize on it, becomes life-long. Becoming a good urologist
requires a highly qualified education and sufficient experience. To devise a
training programme of high proficiency, several important factors must be
considered. There are many studies in the literature revealing the thoughts of
urology residents towards their training, needs and the realities. The aim of
this chapter is to review the new technologies in urology training and show the
new pathway of the future of training in urology.
PMID- 29336347
TI - Electromigration and morphological changes in Ag nanostructures.
AB - Electromigration (EM) as a structuring tool was investigated in Ag nanowires
(width 300 nm, thickness 25 nm) and partly in notched and bow-tie Ag structures
on a Si(1 0 0) substrate in ultra-high vacuum using a four-tip scanning tunneling
microscope in combination with a scanning electron microscope. From simulations
of Ag nanowires we got estimates of temperature profiles, current density
profiles, EM and thermal migration (TM) mass flux distributions within the
nanowire induced by critical current densities of 108 A cm-2. At room
temperature, the electron wind force at these current densities by far dominates
over thermal diffusion, and is responsible for formation of voids at the cathode
and hillocks at the anode side. For current densities that exceed the critical
current densities necessary for EM, a new type of wire-like structure formation
was found both at room temperature and at 100 K for notched and bow-tie
structures. This suggests that the simultaneous action of EM and TM is structure
forming, but with a very small influence of TM at low temperature.
PMID- 29336348
TI - Optimizing highly noncoplanar VMAT trajectories: the NoVo method.
AB - We introduce a new method called NoVo (Noncoplanar VMAT Optimization) to produce
volumetric modulated arc therapy (VMAT) treatment plans with noncoplanar
trajectories. While the use of noncoplanar beam arrangements for intensity
modulated radiation therapy (IMRT), and in particular high fraction stereotactic
radiosurgery (SRS), is common, noncoplanar beam trajectories for VMAT are less
common as the availability of treatment machines handling these is limited. For
both IMRT and VMAT, the beam angle selection problem is highly nonconvex in
nature, which is why automated beam angle selection procedures have not entered
mainstream clinical usage. NoVo determines a noncoplanar VMAT solution (i.e. the
simultaneous trajectories of the gantry and the couch) by first computing a
[Formula: see text] solution (beams from every possible direction, suitably
discretized) and then eliminating beams by examing fluence contributions. Also
all beam angles are scored via geometrical considerations only to find out the
usefulness of the whole beam space in a very short time. A custom path finding
algorithm is applied to find an optimized, continuous trajectory through the most
promising beam angles using the calculated score of the beam space. Finally,
using this trajectory a VMAT plan is optimized. For three clinical cases, a lung,
brain, and liver case, we compare NoVo to the ideal [Formula: see text] solution,
nine beam noncoplanar IMRT, coplanar VMAT, and a recently published noncoplanar
VMAT algorithm. NoVo comes closest to the [Formula: see text] solution
considering the lung case (brain and liver case: second), as well as improving
the solution time by using geometrical considerations, followed by a time
effective iterative process reducing the [Formula: see text] solution. Compared
to a recently published noncoplanar VMAT algorithm, using NoVo the computation
time is reduced by a factor of 2-3 (depending on the case). Compared to coplanar
VMAT, NoVo reduces the objective function value by 24%, 49% and 6% for the lung,
brain and liver cases, respectively.
PMID- 29336349
TI - Nanodoping: a route for enhancing electro-optic performance of bent core nematic
system.
AB - We report the effect of dispersion of barium titanate (BaTiO3) nanoparticles
(BNPs) in a four ring bent core nematic (BCN) liquid crystal. Polarizing optical
microscopy reveals the presence of a single nematic phase in pure and doped
states. Polar switching has been observed in the bent core system and the value
of spontaneous polarization (P s) increases with increase in doping concentration
of BNPs in BCN. Dielectric study shows a lower frequency mode, which can be
ascribed to the formation of cybotactic clusters. These clusters are also
responsible for the observed polar switching in pure, as well as, in doped BCNs.
Another higher frequency mode, observed only in pure BCN, indicates the rotation
of molecules about their long molecular axis. The conductivity of doped samples
is also found to decrease as compared to the pure BCN. This reduction helps in
the minimization of negative effects caused by free ions in liquid crystal based
devices. This study demonstrates that the interaction between BNPs and BCN
molecules improves the P s, dielectric behaviour, viscosity and reduces the
conductivity of pure BCN. Hence, nanodoping in a BCN is an effective method for
the enhancement of electro-optic performances and will lead to the development of
faster electro-optic devices.
PMID- 29336350
TI - Mixed matrix membranes with fast and selective transport pathways for efficient
CO2 separation.
AB - To improve CO2 separation performance, porous carbon nanosheets (PCNs) were used
as a filler into a Pebax MH 1657 (Pebax) matrix, fabricating mixed matrix
membranes (MMMs). The PCNs exhibited a preferential horizontal orientation within
the Pebax matrix because of the extremely large 2D plane and nanoscale thickness
of the matrix. Therefore, the micropores of the PCNs provided fast CO2 transport
pathways, which led to increased CO2 permeability. The reduced pore size of the
PCNs was a consequence of the overlapping of PCNs and the polymer chains
penetrating into the pores of the PCNs. The reduction in the pore size of the
PCNs improved the CO2/gas selectivity. As a result, the CO2 permeability and
CO2/CH4 selectivity of the Pebax membrane with 10 wt% PCNs-loading (Pebax-PCNs
10) were 520 barrer and 51, respectively, for CO2/CH4 mixed-gas. The CO2
permeability and CO2/N2 selectivity of the Pebax-PCNs-10 membrane were 614 barrer
and 61, respectively, for CO2/N2 mixed-gas.
PMID- 29336351
TI - Microwave absorption properties of reduced graphene oxide strontium
hexaferrite/poly(methyl methacrylate) composites.
AB - The key factors to consider when designing microwave absorber materials for
eradication of electromagnetic (EM) pollution are absorption of incident EM waves
and good impedance matching. By keeping these things in mind, flexible microwave
absorber composite films can be fabricated by simple gel casting techniques using
reduced graphene oxide (RGO) and strontium ferrite (SF) in a poly(methyl
methacrylate) (PMMA) matrix. SF nanoparticles are synthesized by the well known
sol-gel method. Subsequently, reduced graphene oxide (RGO) and SF nanocomposite
(RGOSF) are prepared through a chemical reduction method using hydrazine. The
structure, morphology, chemical composition, thermal stability and magnetic
properties of the nanocomposite are characterized in detail by various
techniques. The SF particles are found to be nearly 500 nm and decorated on RGO
sheets as revealed by field emission scanning electron microscopy and
transmission electron microscopy analysis. Fourier transform infrared and and
Raman spectroscopy clearly show the presence of SF in the graphene sheet by the
lower peak positions. Finally, ternary polymer composites of RGO/SF/PMMA are
prepared by an in situ polymerization method. Magnetic and dielectric studies of
the composite reveal that the presence of RGO/SF/PMMA lead to polarization
effects contributing to dielectric loss. Also, RGO surrounding SF provides a
conductive network in the polymer matrix which is in turn responsible for the
magnetic loss in the composite. Thus, the permittivity as well as the
permeability of the composite can be controlled by an appropriate combination of
RGO and SF in PMMA. More than 99% absorption efficiency is achieved by a suitable
combination of magneto-dielectric coupling in the X-band frequency range by
incorporating 9 wt% of RGO and 1 wt% of SF in the polymer matrix.
PMID- 29336352
TI - One-pot synthesis of a PtPd dendritic nanocube cage superstructure on graphenes
as advanced catalysts for oxygen reduction.
AB - How to use Pt economically and efficiently in the oxygen reduction reaction (ORR)
is of theoretical and practical significance for the industrialization of the
proton-exchange membrane fuel cells. In order to minimize Pt consumption and
optimize the ORR performance, the ORR catalysts are recommended to be designed as
a porous nanostructure. Herein, we report a one-pot solvothermal strategy to
prepare PtPd dendritic nanocube cages via a galvanic replacement mechanism
triggered by an I- ion. These PtPd alloy crystals are nanoporous, and uniformly
dispersed on reduced graphene oxides (RGOs). The size of the PtPd dendritic
nanocube cages can be easily tuned from 20-80 nm by controlling their
composition. Their composition is optimized to be 1:5 Pt/Pd atomic ratio for
these RGO-supported PtPd dendritic nanocages. This catalyst shows superior ORR
performance with a specific activity of 2.01 mA cm-2 and a mass activity of 4.45
A mg-1 Pt, far above those for Pt/C catalysts (0.288 mA cm-2 for specific
activity, and 0.21 A mg-1 Pt for mass activity). In addition to ORR activity, it
also exhibits robust durability with almost negligible decay in ORR mass activity
after 10 000 voltammetric cycling.
PMID- 29336353
TI - Perovskite nanocrystals: across-dimensional attachment, film-scale assembly on a
flexible substrate and their fluorescence properties.
AB - Perovskite nanocrystals (NCs), which are a good fluorescence candidate with
excellent photoelectric properties, have opened new avenues in the fabrication of
highly efficient solar cells, light-emitting diodes (LEDs), and other
optoelectronic devices. Further advances will rely on the multitude of
compositional, structural variants that enable the formation of lower
dimensionality layered and three-dimensional (3D) perovskites with architectural
innovations. In this work, the perovskite film was fabricated on a flexible
substrate using simple dip-coating technology and 3D assemblies of perovskite NCs
were obtained through an attachment process. Original perovskite NCs had a
rectangular or square morphology with high particle uniformity and the narrow and
symmetric fluorescence emission peak was adjustable at 515-527 nm. The
controllable self-assembly of the micron size cuboid-like 3D assembly had an
apparent enhancement on peak (111) in the x-ray diffraction (XRD) pattern.
Surface ligands not only play a role in the attachment process but also keep the
independence of each NC in 3D assemblies. Such assembly of the perovskite film
maintained the original perovskite NCs fluorescence emission peak and narrow full
width at the half-maximum (FWHM), which is of great importance for the
investigation of future devices.
PMID- 29336354
TI - An analytical poroelastic model for ultrasound elastography imaging of tumors.
AB - The mechanical behavior of biological tissues has been studied using a number of
mechanical models. Due to the relatively high fluid content and mobility, many
biological tissues have been modeled as poroelastic materials. Diseases such as
cancers are known to alter the poroelastic response of a tissue. Tissue
poroelastic properties such as compressibility, interstitial permeability and
fluid pressure also play a key role for the assessment of cancer treatments and
for improved therapies. At the present time, however, a limited number of
poroelastic models for soft tissues are retrievable in the literature, and the
ones available are not directly applicable to tumors as they typically refer to
uniform tissues. In this paper, we report the analytical poroelastic model for a
non-uniform tissue under stress relaxation. Displacement, strain and fluid
pressure fields in a cylindrical poroelastic sample containing a cylindrical
inclusion during stress relaxation are computed. Finite element simulations are
then used to validate the proposed theoretical model. Statistical analysis
demonstrates that the proposed analytical model matches the finite element
results with less than 0.5% error. The availability of the analytical model and
solutions presented in this paper may be useful to estimate diagnostically
relevant poroelastic parameters such as interstitial permeability and fluid
pressure, and, in general, for a better interpretation of clinically-relevant
ultrasound elastography results.
PMID- 29336355
TI - Evaluation of cardiolipin nanodisks as lipid replacement therapy for Barth
syndrome
AB - Barth syndrome (BTHS) is a mitochondrial disorder characterized by cardiomyopathy
and skeletal muscle weakness. Disease results from mutations in the tafazzin
(TAZ) gene, encoding a phospholipid transacylase. Defective tafazzin activity
results in an aberrant cardiolipin (CL) profile. The feasibility of restoring the
intracellular CL profile was tested by in vivo administration of exogenous CL in
nanodisk (ND) delivery particles. Ninety mg/kg CL (as ND) was administered to
doxycycline-inducible taz shRNA knockdown (KD) mice once a week. After 10 weeks
of CL-ND treatment, the mice were sacrificed and tissues harvested. Liquid
chromatography-mass spectrometry of extracted lipids revealed that CL-ND
administration failed to alter the CL profile of taz KD or WT mice. Thus,
although CL-ND were previously shown to be an effective means of delivering CL to
cultured cells, this effect does not extend to an in vivo setting. We conclude
that CL-ND administration is not a suitable therapy option for BTHS.
PMID- 29336356
TI - Tcf7l1 promotes transcription of Kruppel-likefactor 4 during Xenopus
embryogenesis.
AB - Kruppel-like factor 4 (Klf4) is a zinc finger transcriptionfactor and plays
crucial roles in Xenopus embryogenesis. However, its regulation during
embryogenesis is stillunclear. Here, we report that Tcf7l1, a key downstream
transducerof the Wnt signaling pathway, could promote Klf4 transcription and
stimulate Klf4 promoter activity in early Xenopus embryos. Furthermore,
cycloheximide treatmentshowed a direct effect on Klf4 transcriptionfacilitated by
Tcf7l1. Moreover, the dominant negative form of Tcf7l1(dnTcf7l1), which lacks N
terminusof the beta-catenin binding motif, could still activate Klf4
transcription, suggesting that thisregulation is Wnt/beta-catenin independent.
Taken together, ourresults demonstrate that Tcf7l1 lies upstream of Klf4 to
maintainits expression level during Xenopus embryogenesis.
PMID- 29336357
TI - Distinctive roles of Rac1 and Rab29 in LRRK2 mediated membrane trafficking and
neurite outgrowth.
AB - Parkinson's disease (PD) associated leucine-rich repeat kinase 2 (LRRK2) mutants
have shown pathogenic effects on variety of subcellular processes.Two small
GTPases Rac1 and Rab29 have been indicated as possible downstream effectors
participating in LRRK2 signaling but their detail mechanisms remain unclear. In
this study, we have used biochemical and cell biology approaches to address
whether two GTPases interact with LRRK2 and hence function differently in LRRK2
mediated pathogenesis.Here we show thatRac1 and Rab29 specifically interact with
LRRK2with higher affinity for Rab29and with different preference in functional
domain binding. Mutant Rab29 but not Rac1 alters theendosome-to-TGN retrograde
trafficking of a cargo protein cation-independent mannose-6-phosphate receptor
(CI-M6PR) and its stability. On the other hand, overexpressedwild type Rab29 but
not Rac1 rescue the altered retrograde membrane trafficking induced by the
pathogenic mutant LRRK2G2019S. Furthermore, both Rac1 and Rab29 can rescue the
neurite shortening in differentiated SH-SY5Y cells induced by LRRK2G2019S. Our
study strongly suggests that Rac1 and Rab29 are involved in the distinct
functions as downstream effectors in LRRK2 signaling pathways.
PMID- 29336358
TI - Risk Factors, Regional Disparity and Trends of Ischemic Stroke Etiologic
Subtypes.
PMID- 29336359
TI - White Matter Lesions Predict Recurrent Vascular Events in Patients with Transient
Ischemic Attacks.
AB - BACKGROUND: White matter lesions (WMLs) are common findings in brain magnetic
resonance imaging (MRI) and are strongly associated with stroke incidence,
recurrence, and prognosis. However, the relationship between WMLs and transient
ischemic attacks (TIAs) is not well established. This study aimed to determine
the clinical significance of WMLs in patients with TIA. METHODS: A total of 181
consecutive inpatients with first-ever TIA were enrolled. Brain MRIs within 2
days of symptom onset were used to measure WML volumes. Recurrent vascular events
within 1 year of TIA onset were assessed. The relationship between WMLs and
recurrent risk of vascular events was determined by a multivariate logistic
regression. RESULTS: WMLs were identified in 104 patients (57.5%). Age and ratio
of hypertension were significantly different between patients with and without
WMLs. The incidence of vascular events in patients with WMLs significantly
increased in comparison to those without WMLs (21.15% vs. 5.19%, 95% confidence
interval [CI]: 1.18-15.20, P = 0.027) after controlling for confounders.
Furthermore, distributions of WML loads were found to be different between
patients who developed vascular events and those who did not. WML volumes were
demonstrated to be correlated with recurrent risks, and the fourth quartile of
WML volumes led to an 8.5-fold elevation of recurrent risk of vascular events
compared with the first quartile (95% CI: 1.52-47.65, P = 0.015) after adjusting
for hyperlipidemia. CONCLUSION: WMLs occur frequently in patients with TIA and
are associated with the high risk of recurrent vascular events, suggesting a
predictive neuroimaging marker for TIA outcomes.
PMID- 29336360
TI - Early Neurological Deterioration after Recanalization Treatment in Patients with
Acute Ischemic Stroke: A Retrospective Study.
AB - BACKGROUND: Early neurological deterioration (END) is a prominent issue after
recanalization treatment. However, few studies have reported the characteristics
of END after endovascular treatment (EVT) as so far. This study investigated the
incidence, composition, and outcomes of END after intravenous recombinant tissue
plasminogen activator (IV rt-PA) and EVT of acute ischemic stroke, and identified
risk factors for END. METHODS: Medical records of patients who received
recanalization treatment between January 1, 2014, and December 31, 2015 were
reviewed. Patients were classified into IV rt-PA or EVT group according to the
methods of recanalization treatment. The END was defined as an increase in the
National Institutes of Health Stroke Scale (NIHSS) >=4 or an increase in Ia of
NIHSS >=1 within 72 h after recanalization treatment. Clinical data were compared
between the END and non-END subgroups within each recanalization group. RESULTS:
Of the 278 patients included in the study, the incidence of END was 34.2%. The
incidence rates of END were 29.8% in the IV rt-PA group and 40.2% in the EVT
group. Ischemia progression (68.4%) was the main contributor to END followed by
vasogenic cerebral edema (21.1%) and symptomatic intracranial hemorrhage (10.5%).
Multivariate logistic regression showed that admission systolic blood pressure
(SBP) >=160 mmHg (odds ratio [OR]: 2.312, 95% confidence interval [CI]: 1.105
4.837) and large artery occlusion after IV rt-PA (OR: 3.628, 95% CI: 1.482-8.881)
independently predicted END after IV rt-PA; and admission SBP >=140 mmHg (OR:
5.183, 95% CI: 1.967-13.661), partial recanalization (OR: 4.791, 95% CI: 1.749
13.121), and nonrecanalization (OR: 5.952, 95% CI: 1.841-19.243) independently
predicted END after EVT. The mortality rate and grave outcome rate at discharge
of all the END patients (26.3% and 55.8%) were higher than those of all the non
END patients (1.1% and 18.6%; P < 0.01). CONCLUSIONS: END was not an uncommon
event and associated with death and grave outcome at discharge. High admission
SBP and unsatisfactory recanalization of occluded arteries might predict END.
PMID- 29336361
TI - Muscle Magnetic Resonance Imaging for the Differentiation of Multiple Acyl-CoA
Dehydrogenase Deficiency and Immune-mediated Necrotizing Myopathy.
AB - BACKGROUND: Clinically, it is difficult to differentiate multiple acyl-CoA
dehydrogenase deficiency (MADD) from immune-mediated necrotizing myopathy (IMNM)
because they display similar symptoms. This study aimed to determine whether
muscle magnetic resonance imaging (MRI) could be used for differential diagnosis
between MADD and IMNM. METHODS: The study evaluated 25 MADD patients, confirmed
by muscle biopsy and ETFDH gene testing, and 30 IMNM patients, confirmed by
muscle biopsy. Muscles were assessed for edema and fatty replacement using thigh
MRI (tMRI). Degrees and distribution patterns of fatty infiltration and edema in
gluteus maximus and thigh muscles were compared. RESULTS: Total fatty
infiltration and edema scores (median, [Q1, Q3]) were 4.00 (1.00, 15.00) and 0
(0, 4.00) in MADD and 14.50 (8.00, 20.75) and 22.00 (16.75, 32.00) in IMNM,
respectively, which were significantly more severe in IMNM than that in MADD (P =
0.000 and P = 0.004, respectively). Edema scores for gluteus maximus, long head
of biceps femoris, and semimembranosus were significantly higher in IMNM than in
MADD (all P = 0.000). Fatty infiltration scores for anterior and medial
compartments were significantly more severe in IMNM than that in MADD (all P =
0.000). CONCLUSION: Different patterns of muscle involvement on tMRI can
contribute to differential diagnosis between MADD and IMNM when clinical
suspicions alone are insufficient, thereby reducing the need for muscle biopsy.
PMID- 29336362
TI - Screening for SH3TC2, PMP2, and BSCL2 Variants in a Cohort of Chinese Patients
with Charcot-Marie-Tooth.
AB - BACKGROUND: SH3TC2, PMP2, and BSCL2 genes are related to autosomal recessive (AR)
Charcot-Marie-Tooth (CMT) disease type 1, autosomal dominant (AD)-CMT1, and AD
CMT2, respectively. Pathogenic variants in these three genes were not well
documented in Chinese CMT patients. Therefore, this study aims to detect SH3TC2,
PMP2, and BSCL2 pathogenic variants in a cohort of 315 unrelated Chinese CMT
families. METHODS: A total of 315 probands from 315 unrelated Chinese CMT
families were recruited from the Department of Neurology of Third Xiangya
Hospital and Xiangya Hospital. We screened for SH3TC2 pathogenic variants in 84
AR or sporadic CMT probands, PMP2 pathogenic variants in 39 AD or sporadic CMT1
probands, and BSCL2 pathogenic variants in 50 AD or sporadic CMT2 probands, using
polymerase chain reaction and Sanger sequencing. All these patients were out of
315 unrelated Chinese CMT families and genetically undiagnosed after exclusion of
pathogenic variants of PMP22, MFN2, MPZ, GJB1, GDAP1, HSPB1, HSPB8, EGR2, NEFL,
and RAB7. Candidate variants were analyzed based on the standards and guidelines
of American College of Medical Genetics and Genomics (ACMG). Clinical features
were reevaluated. RESULTS: We identified three novel heterozygous variants such
as p.L95V (c.283C>G), p.L1048P (c.3143T>C), and p.V1105M (c.3313G>A) of SH3TC2
gene and no pathogenic variants of PMP2 and BSCL2 genes. Although evaluation in
silico and screening in the healthy control revealed that the three SH3TC2
variants were likely pathogenic, no second allele variants were discovered.
According to the standards and guidelines of ACMG, the heterozygous SH3TC2
variants such as p.L95V, p.L1048P, and p.V1105M were considered to be of
uncertain significance. CONCLUSIONS: SH3TC2, PMP2, and BSCL2 pathogenic variants
might be rare in Chinese CMT patients. Further studies to confirm our findings
are needed.
PMID- 29336363
TI - Utility and Safety of Intrathecal Methotrexate Treatment in Severe Anti-N-methyl
D-aspartate Receptor Encephalitis: A Pilot Study.
AB - BACKGROUND: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a
treatable autoimmune neurologic syndrome that occurs with or without tumor
association. However, some severe cases are refractory to systemic immunotherapy.
This pilot study aimed to evaluate the utility and safety of intrathecal
methotrexate injection for severe patients with anti-NMDAR encephalitis who did
not respond to first-line immunotherapy. METHODS: Intrathecal injections with
methotrexate and dexamethasone were performed weekly in four legible patients
within consecutive 4 weeks. Cerebrospinal fluid (CSF) was collected at baseline
and each time of intrathecal injection for identification of anti-NMDAR antibody
titers. RESULTS: Significant clinical improvement was observed in three patients
associated with a stepwise decrease of CSF anti-NMDAR antibody titers (maximum:
1/320 to minimum: 1/10). After 2 months of follow-up, they were able to follow
simple commands and had appropriate interactions with people (modified Rankin
scale [mRS] of 0-2). At 12 months of follow-up, they all had returned to most
activities of daily life (mRS of 0), and no relapses were reported. One patient
showed no clinical improvement and died of neurologic complications. CONCLUSIONS:
Intrathecal treatment may be a potentially useful supplementary therapy in
severely affected patients with anti-NMDAR encephalitis. Further large cohort
study and animal experiment may help us elaborate the utility of intrathecal
injection of methotrexate and its mechanism of action.
PMID- 29336364
TI - Mechanism of Chronic Stress-induced Reduced Atherosclerotic Medial Area and
Increased Plaque Instability in Rabbit Models of Chronic Stress.
AB - BACKGROUND: Chronic stress contributes to increased risks of atherosclerotic
diseases including heart disease, stroke, and transient ischemic attack. However,
its underline mechanisms are poorly understood. This study aimed to elucidate the
mechanism via which chronic stress exerts its effect on atherosclerosis (AS).
METHODS: Fifty male New Zealand white rabbits were used. Aortic balloon-injury
model was applied. Both social stress and physical stress methods were adopted to
establish chronic stress models. The lumen stenotic degree, intimal and medial
areas, maximum fibrous cap thickness, and plaque contents were measured with
histological sections. Proteomic methods were applied to detect protein changes
in abdominal aortas to identify the specialized mediators. Real-time reverse
transcription-polymerase chain reaction was used for further verification and
investigation. RESULTS: The stress rabbits exhibited lower body weight, worse fur
state, more inactivity behavior, and higher serum cortisol level. Chronic stress
was significantly associated with the decreased medial area and increased plaque
instability, which was manifested by thinner fibrous caps, larger lipid cores,
more macrophages, and new vessels but fewer smooth muscle cells and elastic
fibers. After chronic stress, the apoptosis-related genes UBE2K, BAX, FAS,
Caspase 3, Caspase 9, and P53 were upregulated, and BCL-2/BAX was down-regulated;
the angiogenesis-related genes ANG and VEGF-A were also highly expressed in
atherosclerotic arteries. CONCLUSIONS: Rabbit models of chronic stress were
successfully established by applying both social stress and physical stress for 8
weeks. Chronic stress can reduce AS tunica media and accelerate plaque
instability by promoting apoptosis and neovascularization.
PMID- 29336365
TI - IL1F7 Gene Polymorphism Is not Associated with Rheumatoid Arthritis
Susceptibility in the Northern Chinese Han Population: A Case-Control Study.
AB - BACKGROUND: Interleukin (IL)-37, also called IL1F7, is a natural inhibitor of
inflammatory and immune responses. It is involved in the pathogenesis of
rheumatoid arthritis (RA). This study aimed to investigate the role of IL1F7 gene
polymorphism in RA susceptibility in a large cohort of patients. METHODS: Five
selected single-nucleotide polymorphisms in IL1F7 genes (rs2723186, rs3811046,
rs4241122, rs4364030, and rs4392270) were genotyped by TaqMan Allelic
Discrimination in Northern Chinese Han population. The allele and the genotype
were compared between patients with RA and healthy controls. Association analyses
were performed on the entire data set and on different RA subsets based on the
status of the anti-cyclic citrullinated peptide antibody and the rheumatoid
factor by logistic regression, adjusting for age and gender. RESULTS: Trend
associations were detected between rs2723186, rs4241122, rs4392270, and RA in
Stage I (160 patients with RA; 252 healthy controls). Further validation in Stage
II comprised 730 unrelated patients with RA (mean age: 54.9 +/- 12.6 years; 81.6%
females) and 778 unrelated healthy individuals (mean age: 53.5 +/- 15.7 years;
79.5% females). No significant differences in the distributions of alleles and
genotypes were observed between the case and control groups in both the entire
set and the different RA subsets. Disease activity and age of RA onset were also
not associated with genotype distributions. CONCLUSION: IL1F7 gene polymorphism
does not significantly influence RA susceptibility in the Northern Chinese Han
population.
PMID- 29336366
TI - Potential Value of Datura stramonium Agglutinin-recognized Glycopatterns in
Urinary Protein on Differential Diagnosis of Diabetic Nephropathy and Nondiabetic
Renal Disease.
AB - BACKGROUND: Diabetic nephropathy (DN) is the most common and serious
microvascular complication of diabetes. To date, the gold standard for
identifying DN and nondiabetic renal disease (NDRD) is a renal biopsy; however,
there is currently no reliable diagnostic marker to identify DN and NDRD in a
noninvasive manner. This study aimed to investigate the different glycopatterns
in urine specimens of DN patients and NDRD patients for a differential diagnosis.
METHODS: In total, 19 DN patients and 18 NDRD patients who underwent renal
biopsies between March 2015 and March 2016 at the Chinese People's Liberation
Army General Hospital were enrolled in this study. A lectin microarray was used
to investigate the glycopatterns in the urinary protein of the 37 patients. Ratio
analysis and one-way analysis of variance were used to screen altered
glycopatterns. Then, the altered glycopatterns between the DN and NDRD groups
were verified by a urinary protein microarray among another 32 patients (15 with
DN and 17 with NDRD), and receiver operating characteristic (ROC) curve analysis
was used to determine the diagnostic value of the altered glycopatterns in
differentiating DN and NDRD. Finally, lectin blotting was used to evaluate the
altered glycosylation in protein level. RESULTS: The result of lectin microarrays
revealed that the relative abundance of the (beta-1,4)-linked N-acetyl-D
glucosamine (GlcNAc) recognized by lectin Datura stramonium agglutinin (DSA) was
significantly higher in urinary protein in DN patients than that in NDRD patients
(fold change >1.50, P < 0.001). Subsequently, the results of urinary protein
microarrays were consistent with lectin microarrays (P < 0.05). Furthermore, the
ROC curve showed that glycopatterns could effectively distinguish DN from NDRD
patients (area under the ROC curve = 0.94, P < 0.001). DSA lectin blotting showed
that glycoproteins, with a molecular weight of approximately 50,000, demonstrated
a difference in urine samples between DN patients and NDRD patients. CONCLUSIONS:
The relative abundance of (beta-1,4)-linked GlcNAc recognized by lectin DSA and
urinary glycoprotein with a molecular weight of approximately 50,000 are
significantly different between DN and NDRD patients, indicating that the
glycopatterns could be used as potential biomarkers for a differential diagnosis.
PMID- 29336367
TI - Reduction of Tat-interacting Protein 30 Expression Could be a Prognostic Marker
in Bladder Urothelial Cancer.
AB - BACKGROUND: Tat-interacting protein 30 (TIP30) has been reported to be a tumor
suppressor, with reduced or absent expression in various tumors. However, its
role in bladder urothelial cancer (BUC) has not been investigated. Therefore,
herein, we investigated the expression of TIP30 protein in BUC and normal bladder
mucosa and the clinical significance of TIP30 expression in the prognosis of BUC.
METHODS: We reviewed data from 79 cases of BUC and 15 adjacent tissue samples
from 79 patients treated at our institution between 2004 and 2007. TIP30
expression was examined by immunohistochemistry. The relationship between TIP30
expression and tumor stage, histological grade, and survival was analyzed.
Differences between groups were evaluated using the t-test or matched-pairs test,
and differences in the survival rates were analyzed with the log-rank test.
RESULTS: TIP30 protein expression was significantly reduced in BUC tissue (t =
6.91, P < 0.05) compared with normal tissue samples, and in invasive bladder
cancer (t = 10.89, P < 0.05) compared with superficial bladder cancer. TIP30
protein expression differed significantly among different differentiated groups
classified either according to the World Health Organization (2004, F = 17.48, P
< 0.01) or World Health Organization (1973, F = 10.68, P < 0.01). TIP30 protein
expression was significantly reduced in high-grade papillary urothelial carcinoma
compared with papillary urothelial neoplasm of low malignant potential (P < 0.05)
and low-grade papillary urothelial carcinoma (P < 0.05). Meanwhile, TIP30 protein
expression was significantly reduced in Grade III BUC, compared with Grade I (P <
0.05) and Grade II (P < 0.05). Patients with low TIP30 expression showed a higher
incidence of disease progression than those with high TIP30 expression (t = 2.63,
P < 0.05). Kaplan-Meier survival analysis showed a strong positive relationship
between TIP30 expression and overall survival (OS) (chi2 = 17.29, P < 0.05).
CONCLUSIONS: TIP30 expression was associated with clinical tumor stage in BUC,
suggesting that it might play an important role in disease progression.
Furthermore, TIP30 might predict postoperative OS. Thus, its evaluation might be
useful for predicting prognosis.
PMID- 29336368
TI - Glycosaminoglycan Content of the Lateral Compartment Cartilage in Knees
Conforming to the Indications for Oxford Medial Unicompartmental Knee
Arthroplasty.
AB - BACKGROUND: The quality of the lateral compartment cartilage is important to
preoperative evaluation and prognostic prediction of unicompartmental knee
arthroplasty (UKA). Delayed gadolinium-enhanced magnetic resonance imaging of
cartilage (dGEMRIC) enables noninvasive assessment of glycosaminoglycan (GAG)
content in cartilage. This study aimed to determine the GAG content of the
lateral compartment cartilage in knees scheduled to undergo Oxford medial UKA.
METHODS: From December 2016 to May 2017, twenty patients (20 osteoarthritic
knees) conforming to the indications for Oxford medial UKA were included as the
osteoarthritis (OA) group, and 20 healthy volunteers (20 knees) paired by sex,
knee side, age (+/-3 years), and body mass index (BMI) (+/-3 kg/m2) were included
as the control group. The GAG contents of the weight-bearing femoral cartilage
(wbFC), the posterior non-weight-bearing femoral cartilage (pFC), the lateral
femoral cartilage (FC), and tibial cartilage (TC) were detected using dGEMRIC.
The dGEMRIC indices (T1Gd) were calculated in the middle three consecutive slices
of the lateral compartment. Paired t-tests were used to compare the T1Gd in each
region of interest between the OA group and control group. RESULTS: The average
age and BMI in the two groups were similar. In the OA group, T1Gd of FC and TC
was 386.7 +/- 50.7 ms and 429.6 +/- 59.9 ms, respectively. In the control group,
T1Gd of FC and TC was 397.5 +/- 52.3 ms and 448.6 +/- 62.5 ms, respectively. The
respective T1Gd of wbFC and pFC was 380.0 +/- 47.8 ms and 391.0 +/- 66.3 ms in
the OA group and 400.3 +/- 51.5 ms and 393.6 +/- 57.9 ms in the control group.
Although the T1Gd of wbFC and TC tended to be lower in the OA group than the
control group, there was no significant difference between groups in the T1Gd in
any of the analyzed cartilage regions (P value of wbFC, pFC, FC, and TC was
0.236, 0.857, 0.465, and 0.324, respectively). CONCLUSIONS: The GAG content of
the lateral compartment cartilage in knees conforming to indications for Oxford
medial UKA is similar with those of age- and BMI-matched participants without OA.
PMID- 29336369
TI - Pedicle Subtraction Osteotomy with a Cage Prevents Sagittal Translation in the
Correction of Kyphosis in Ankylosing Spondylitis.
AB - BACKGROUND: Sagittal translation (ST) is an accidental event that surgeons
commonly encounter during a spinal osteotomy in the correction of kyphosis in
ankylosing spondylitis (AS). However, there is a paucity of effective techniques
to prevent ST. The purpose of this study was to propose a pedicle subtraction
osteotomy (PSO) with a cage as a method to prevent ST and to explore the efficacy
and feasibility of this method in the treatment of kyphosis in AS. METHODS: We
retrospectively reviewed 89 consecutive patients with AS kyphosis who underwent a
PSO (Group B, 46 patients) or a PSO with a cage (Group A, 43 patients) from
February 2009 to December 2013. Pre- and post-operative radiographic results were
reviewed. ST and complications were analyzed in both groups. Clinical assessment
was performed using the Scoliosis Research Society-22 (SRS-22) outcomes metric.
The patients were followed up for at least 2 years. RESULTS: Group A achieved the
same re-alignment of the kyphotic spine as Group B. Two (4.7%) of the 43 patients
in Group A and 14 (30.4%) of the 46 patients in Group B had intraoperative ST
(chi2 = 10.020, P = 0.002). Significant differences were identified between the
two groups in the height change of the osteotomized column. SRS-22 scores
improved significantly in both groups. Seven patients experienced neurologic
complications (1 in Group A and 6 in Group B). Eight patients had cerebrospinal
fluid leakage (2 in Group A and 6 in Group B). CONCLUSION: PSO with a cage
significantly avoided ST during the osteotomy procedure and might represent a
new, safe, and feasible choice for treating patients with AS kyphosis.
PMID- 29336370
TI - Differences of Matrix Metalloproteinase 2 Expression between Left and Right
Ventricles in Response to Nandrolone Decanoate and/or Swimming Training in Mice.
AB - BACKGROUND: Matrix metalloproteinase (MMP)-2 plays an important role in the
remodeling of left ventricles (LVs) and right ventricles (RVs). We investigated
the differences of MMP-2 expression between LV and RV in response to nandrolone
decanoate (ND), swimming training (ST), and combined ND and ST (NS) in mice,
based on their structural, functional, and biochemical characteristics. METHODS:
Totally 28 male C57B1 mice (6 weeks old; 20-23 g) were divided into four groups,
including the control (n = 7), ND (n = 6), ST (n = 8), and NS (n = 7) groups.
After respective treatments for 8 weeks, echocardiographic examination was used
to assess the cardiac structure and function. Van Gieson stain was used to
examine the fibrosis of LV and RV in response to different treatments, and
Western blotting analysis was performed to explore different MMP-2 expressions
between LV and RV in response to ND and/or ST. Analysis of variance was used for
comparing the four groups. RESULTS: At 8 weeks, right ventricular dimension/body
weight in the ND group was larger than the other three groups (F = 7.12, P <
0.05) according to the echocardiographic examination. Fibrosis induced by ND
administration was increased more in RV (2.59%) than that in LV (2.21%). MMP-2
expression of the ND group in RV was significantly greater than the control and
NS groups in RV and the corresponding ND group in LV. CONCLUSION: The
experimental data support the hypothesis that ND administration induces greater
MMP-2 expression increase in RV compared to LV, leading to consequent RV
dilation.
PMID- 29336371
TI - In vitro Flow Perfusion Maintaining Long-term Viability of the Rat Groin Fat
Flap: A Novel Model for Research on Large-scale Engineered Tissues.
AB - BACKGROUND: Large-scale muscle tissue engineering remains a major challenge. An
axial vascular pedicle and perfusion bioreactor are necessary for the development
and maintenance of large-scale engineered muscle to ensure circulation within the
construct. We aimed to develop a novel experimental model of a large-scale
engineered muscle flap from an existing rat groin fat flap. METHODS: A fat flap
based on the superficial inferior epigastric vascular pedicle was excised from
rats and placed into a perfusion bioreactor. The flaps were kept in the
bioreactor for up to 7 weeks, and transdifferentiation of adipose to muscle
tissue could have taken place. This system enabled myogenic-differentiation
medium flow through the bioreactor at constant pH and oxygen concentration.
Assessment of viability was performed by an immunofluorescence assay,
histological staining, a calcein-based live/dead test, and through determination
of RNA quantity and quality after 1, 3, 5, and 7 weeks. RESULTS:
Immunofluorescence staining showed that smooth muscle around vessels was still
intact without signs of necrosis or atrophy. The visual assessment of viability
by the calcein-based live/dead test revealed viability of the rat adipose tissue
preserved in the bioreactor system with permanent perfusion. RNA samples from
different experimental conditions were quantified by spectrophotometry, and
intact bands of 18S and 28S rRNA were detected by gel electrophoresis, indicating
that degradation of RNA was minimal. CONCLUSIONS: Flow perfusion maintains the
long-term viability of a rat groin engineered muscle flap in vitro, and a large
scale vascularized muscle could be engineered in a perfusion bioreactor.
PMID- 29336372
TI - Effects of Matricaria chamomilla Extract on Growth and Maturation of Isolated
Mouse Ovarian Follicles in a Three-dimensional Culture System.
AB - BACKGROUND: The aim of this study was to design and assess the effects of
hydroalcoholic extract of Matricaria chamomilla (MC) on preantral follicle
culture of mouse ovaries in a three-dimensional culture system. METHODS: Isolated
preantral follicles were randomly divided into three main groups: the control
group containing 10% fetal bovine serum without MC extract (G1), the first
experimental group supplemented with 25 MUg/ml hydroalcoholic extract of
chamomile (G2), and the second experimental group supplemented with 50 MUg/ml
hydroalcoholic extract of chamomile (G3). RESULTS: After 12 days of culture, the
survival rate (P < 0.05), antrum formation (P < 0.01), metaphase two oocytes (P <
0.01), and the expression of PCNA (P < 0.05) and FSHR (P < 0.05) genes
significantly decreased in G3 as compared with G1. On the other hand, at the last
day of culture (day 12), the mean diameter of follicles cultured in the medium
which was supplemented with 50 MUg/ml hydroalcoholic extract of chamomile
significantly decreased as compared with the G1 (P < 0.05). In addition, the
levels of progesterone and dehydroepiandrosterone hormones significantly
increased in the medium of G3 relative to G1 (P < 0.01), while in the medium of
G1, the level of 17beta-estradiol was significantly higher than that of other
groups (P < 0.01). Reactive oxygen species levels of metaphase II oocytes were
significantly decreased in G2 as compared with G1 (P < 0.01). CONCLUSION: Adding
chamomile extract to culture media appeared to decrease follicular function and
development.
PMID- 29336373
TI - Advances of Long Noncoding RNAs-mediated Regulation in Reproduction.
AB - OBJECTIVE: Advances in genomics and molecular biology have led to the discovery
of a large group of uncharacterized long noncoding RNAs (lncRNAs). Emerging
evidence indicated that many lncRNAs function in multiple biological processes
and its dysregulation often causes diseases. Recent studies suggested that almost
all regulatory lncRNAs interact with biological macromolecules such as DNA, RNA,
and protein. LncRNAs regulate gene expression mainly on three levels, including
epigenetic modification, transcription, and posttranscription, through DNA
methylation, histone modification, and chromatin remodeling. LncRNAs can also
affect the development of diseases and therefore be used to diagnose and treat
diseases. With new sequencing and microarray techniques, hundreds of lncRNAs
involved in reproductive disorders have been identified, but their functions in
these disorders are undefined. DATA SOURCES: This review was based on articles
published in PubMed databases up to July 10, 2017, with the following keywords:
"long noncoding RNAs", "LncRNA", "placentation", and "reproductive diseases".
STUDY SELECTION: Original articles and reviews on the topics were selected.
RESULTS: LncRNAs widely participate in various physiological and pathological
processes as a new class of important regulatory factors. In spermatogenesis,
spermatocytes divide and differentiate into mature spermatozoa. The whole process
is elaborately regulated by the expression of phase-specific genes that involve
many strains of lncRNAs. Literature showed that lncRNA in reproductive cumulus
cells may contribute to the regulation of oocyte maturation, fertilization, and
embryo development. CONCLUSIONS: LncRNA has been found to play a role in the
development of reproduction. Meanwhile, we reviewed the studies on how lncRNAs
participate in reproductive disorders, which provides a basis for the study of
lncRNA in reproduction regulation.
PMID- 29336375
TI - Spontaneous Rupture and Thrombosis of Right Atrium.
PMID- 29336374
TI - Radiotherapy for Gastrointestinal Stromal Tumors.
AB - OBJECTIVE: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors of
the gastrointestinal tract, which frequently cause intraabdominal metastases. The
current standard of care is surgery for localized cases, and adjuvant imatinib is
recommended for tumors with a high risk of recurrence. To date, radiotherapy has
not been commonly accepted as a part of multimodality treatment approach other
than palliation. However, recently published case reports and some small series
suggest that radiotherapy is a valuable option for controlling locally
progressive, drug-resistant disease. The aim of this review is to provide a
viewpoint from a radiation oncologist concerning the management of GISTs,
especially rectal GIST, and clarify the role and technical aspects of
radiotherapy in the treatment approach. DATA SOURCES: A comprehensive search in
PubMed using the keywords "radiotherapy for rectal GIST" and "rectal GIST" was
undertaken. The literature search included the related articles after 1995. STUDY
SELECTION: The main articles including rectal GIST case reports and GIST series
containing rectal cases were the primary references. RESULTS: Surgery is the
mainstay of treatment. However, to date, radiotherapy is included in the
multidisciplinary treatment strategy of rectal GISTs in some circumstances with
palliative, adjuvant, or definitive intent using different treatment doses and
fields. CONCLUSIONS: Recently reported long-term local control rates indicate
that GIST is a radiosensitive disease. This makes radiotherapy a valuable
alternative in GIST management with curative intent, especially in patients who
(1) cannot tolerate or are resistant to chemotherapy agents, (2) have an
unresectable disease, (3) have a gross or microscopic residual disease after
surgery, and (4) have a recurrent disease.
PMID- 29336376
TI - Papillary Glioneuronal Tumor with an Excessive Angiomatous Component in an
Elderly Man.
PMID- 29336377
TI - Pulmonary Capillary Hemangiomatosis without Pulmonary Hypertension: An Early
Stage of Disease?
PMID- 29336378
TI - Reliability and Accuracy of Sepsis-related Organ Failure Assessment Scoring among
Emergency Physicians.
PMID- 29336379
TI - Recurrent Viral Infections Complicated with Cold Agglutinin Disease after
Splenectomy for Thrombocytopenia.
PMID- 29336380
TI - Iron Overload and Hepatitis C Virus Infection.
PMID- 29336381
TI - Reply to "Iron Overload and Hepatitis C Virus Infection".
PMID- 29336382
TI - Atrioventricular septal defects.
PMID- 29336383
TI - Perioperative renal protection during cardiac surgery: A choice between dopamine
and dexmedetomidine.
PMID- 29336384
TI - Noninvasive ventilation using bipap: Expanding indications to post cardiac
surgery care.
PMID- 29336385
TI - Prophylaxis of postoperative nausea and vomiting after cardiac surgery in high
risk patients: A randomized controlled study.
AB - CONTEXT: The role of prophylaxis for postoperative nausea and vomiting (PONV) in
cardiac surgery is under debate. AIMS: To study the risk factors for PONV after
cardiac surgery and the role of betamethasone with or without droperidol for its
prevention. SETTING AND DESIGN: Randomized open-label controlled study comparing
standard care with PONV prophylaxis from February to November 2016. METHODS: Five
hundred and two patients with planned nonemergent cardiac surgery were included.
INTERVENTIONS: In the intervention arm, PONV prophylaxis (4 mg betamethasone
with/without 0.625 mg droperidol) was administered in high-risk patients (two or
more risk factors). Patients in the control arm were treated as per routine
hospital practices. RESULTS: Female sex, past history of PONV, and migraines were
associated with a significantly increased risk of PONV, while motion sickness,
smoking status, and volatile anesthetics were not. Pain and treatment with
nefopam or ketoprofen were associated with an increased risk of PONV. PONV was
less frequent in the active arm compared to controls (45.5% vs. 54.0%, P = 0.063;
visual analogic scale 10.9 vs. 15.3 mm, P = 0.043). Among the 180 patients
(35.6%) with >=2 risk factors, prophylaxis was associated with reduced PONV
(intention-to-treat: 46.8% vs. 67.8%, P = 0.0061; per-protocol: 39.2% vs. 69%, P
= 0.0002). In multivariate analysis, prophylaxis was independently associated
with PONV (odds ratio [OR]: 0.324, 95% confidence interval: 0.167-0.629, P =
0.0009), as were female sex, past history of PONV, and migraines (OR: 3.027,
3.031, and 2.160 respectively). No drug-related side effects were reported.
CONCLUSION: Betamethasone with/without droperidol was effective in decreasing
PONV in high risk cardiac surgical patients without any side effect.
PMID- 29336386
TI - Retrospective study of complete atrioventricular canal defects: Anesthetic and
perioperative challenges.
AB - OBJECTIVE: The objective of this study was to highlight anesthetic and
perioperative management and the outcomes of infants with complete
atrioventricular (AV) canal defects. DESIGN: This retrospective descriptive study
included children who underwent staged and primary biventricular repair for
complete AV canal defects from 1999 to 2013. SETTING: A single-center study at a
university affiliated heart center. PARTICIPANTS: One hundred and fifty-seven
patients with a mean age at surgery of 125 +/- 56.9 days were included in the
study. About 63.6% of them were diagnosed as Down syndrome. Mean body weight at
surgery was 5.6 +/- 6.3 kg. METHODS: Primary and staged biventricular repair of
complete AV canal defects. MEASUREMENTS AND MAIN RESULTS: A predefined protocol
including timing of surgery, management of induction and maintenance of
anesthesia, cardiopulmonary bypass, and perioperative intensive care treatment
was used throughout the study. Demographic data as well as intraoperative and
perioperative Intensive Care Unit (ICU) data, such as length of stay in ICU,
total duration of ventilation including reintubations, and total length of stay
in hospital and in hospital mortality, were collected from the clinical
information system. Pulmonary hypertension was noted in 60% of patients from
which 30% needed nitric oxide therapy. Nearly 2.5% of patients needed permanent
pacemaker implantation. Thorax was closed secondarily in 7% of patients. In 3.8%
of patients, reoperations due to residual defects were undertaken. Duration of
hospital stay was 14.5 +/- 4.7 days. The in-hospital mortality was 0%.
CONCLUSION: Protocolized perioperative management leads to excellent outcome in
AV canal defect repair surgery.
PMID- 29336387
TI - Dexmedetomidine for prevention of skeletal muscle ischaemia-reperfusion injury in
patients with chronic limb ischaemia undergoing aortobifemoral bypass surgery: A
prospective double-blind randomized controlled study.
AB - BACKGROUND: Dexmedetomidine is a selective alpha-2 agonist used for sedation. It
has also been shown to have myocardial protective effect and prevent ischemia
reperfusion injury in off-pump coronary artery bypass patients. The aim of our
study was to assess the effect of dexmedetomidine for prevention of skeletal
muscle ischemia-reperfusion injury in patients undergoing aortobifemoral bypass
surgery. METHODOLOGY: Sixty adult patients (Group dexmedetomidine n = 30, Group
normal saline n = 30) undergoing aortobifemoral bypass surgery were recruited
over 3 months. Randomization was done using a computer-generated random table.
The attending anesthesiologist would be blinded to whether the drug/normal saline
was being administered. He would consider each unlabeled syringe as containing
dexmedetomidine and calculate the volume to be infused via a syringe pump
accordingly. Dexmedetomidine infusion (1 mcg/kg) over 15 minutes was given as a
loading dose, followed by maintenance infusion of 0.5 mcg/kg/h till 2 h
postprocedure in Group dexmedetomidine (D) while the same volume of normal saline
was given in the control Group C till 2 h postprocedure. Creatine phosphokinase
(CPK) values were noted at baseline (T0), 6 h (T1), 12 h (T2), and 24 h (T3)
after the procedure. Hemodynamic variables (heart rate [HR] and mean blood
pressure [MAP]) were recorded at T0, T1, T2, and T3. Results were analyzed using
unpaired Student's t-test, P < 0.05 was considered statistically significant.
RESULTS: MAP and HR significantly decreased in Group D as compared to control
group (P < 0.05). However, the decrease was never <20% of the baseline. The CPK
values at 6, 12, and 24 h were statistically significant between the two groups.
CONCLUSION: Dexmedetomidine prevents skeletal muscle ischemia-reperfusion injury
in patients undergoing aortobifemoral bypass surgery.
PMID- 29336388
TI - Assessment the effect of dexmedetomidine on incidence of paradoxical hypertension
after surgical repair of aortic coarctation in pediatric patients.
AB - OBJECTIVE: The aim of the study was to assess the effect of dexmedetomidine on
the incidence of paradoxical hypertension in patients undergoing aortic
coarctation repair. DESIGN: Randomized observational study. SETTING: University
hospital and cardiac center. PATIENTS: The study included 108 pediatric patients
with isolated aortic coarctation. METHODS: The patients were classified into two
groups (each = 54): Group D: the patients received dexmedetomidine as a loading
dose of 0.5 MUg/kg over 10 min followed by infusion 0.3 MUg/kg/h during surgery
and continued for the first 48 postoperative hours. Group C: The patients
received an equal amount of normal saline. The medication was prepared by the
nursing staff and given to anesthetist blindly. The collected data included the
heart rate, systolic and diastolic arterial blood pressure, incidence, onset,
severity and treatment of paradoxical hypertension, fentanyl dose and end-tidal
sevoflurane concentration, amount of blood loss and urine output. MAIN RESULTS:
The heart rate, systolic and diastolic blood pressure decreased significantly
with dexmedetomidine than Group C (P < 0.05). The incidence and severity of the
paradoxical hypertension was lower with dexmedetomidine than Group C (P = 0.011,
P = 0.017, respectively). The onset the paradoxical hypertension was earlier in
Group C than dexmedetomidine (P = 0.026). The dose of fentanyl and sevoflurane
concentration decreased significantly with dexmedetomidine (P = 0.034, P = 0.026,
respectively). The blood loss decreased with dexmedetomidine (P = 0.020) and the
urine output increased with dexmedetomidine (P = 0.024). The incidence of
hypotension and bradycardia was more with dexmedetomidine (P < 0.05). CONCLUSION:
Dexmedetomidine is safe in pediatric patients undergoing aortic coarctation
repair. It minimized the incidence and severity of paradoxical hypertension. It
decreased the required antihypertensive medications.
PMID- 29336390
TI - Long-term quality of life postacute kidney injury in cardiac surgery patients.
AB - BACKGROUND: Acute renal failure after cardiac surgery is known to be associated
with significant short-term morbidity and mortality. There have as yet been no
major reports on long-term quality of life (QOL). This study assessed the impact
of acute kidney injury (AKI) and renal replacement therapy (RRT) on long-term
survival and QOL after cardiac surgery. The need for long-term RRT is also
assessed. MATERIALS AND METHODS: Patients who underwent cardiac surgery between
2005 and 2011 (n = 6087) and developed AKI (RIFLE criteria, n = 570) were
included. They were propensity-matched 1:1 to patients without renal impairment
(control). Data were prospectively collected, and health-related QOL
questionnaire was sent to patients who were alive at least 1-year postoperatively
at the time of the study. RESULTS: There was no significant difference in the
preoperative characteristics between the two groups (age, gender, left
ventricular ejection fraction, procedure, urgency, logistic Euroscore),
respectively. Median follow-up was 52 months. Survival data were available in all
patients. Questionnaires were returned in 64% of eligible patients. Long-term
survival was significantly lower, and QOL, in particular the physical aspect, was
significantly worse for the AKI group as compared to non-AKI group (38.8 vs.
44.2, P = 0.002), especially so in patients who required RRT. In alive
respondents, despite an 18% (66/359) incidence of ongoing renal follow-up, the
need for late RRT was only in 1.1% (4/359). CONCLUSION: AKI and especially the
need for RRT following cardiac surgery are associated with increased long-term
mortality as well as worse quality of life in a propensity-matched control group.
PMID- 29336389
TI - A randomized controlled trial comparing the myocardial protective effects of
isoflurane with propofol in patients undergoing elective coronary artery bypass
surgery on cardiopulmonary bypass, assessed by changes in N-terminal brain
natriuretic peptide.
AB - OBJECTIVE: The objective of the study is to compare the myocardial protective
effects of isoflurane with propofol in patients undergoing elective coronary
artery bypass surgery on cardiopulmonary bypass (CPB), the cardio protection been
assessed by changes in N-terminal brain natriuretic peptide (NT proBNP).
Methodology and Design: This study is designed as a participant blinded,
prospective randomized clinical trial. SETTING: Christian Medical College
Hospital, Vellore, India. PARTICIPANTS: Patients undergoing elective coronary
artery bypass surgery on CPB. INTERVENTION: Anesthesia was maintained with 0.8
1.2 end tidal concentrations of isoflurane in the isoflurane group and in the
propofol group, anesthesia was maintained with propofol infusion as described by
Roberts et al. MEASUREMENTS: Hemodynamic data were recorded at frequent intervals
during the surgery and up to 24 h in the Intensive Care Unit (ICU). The other
variables that were measured include duration of mechanical ventilation, dose and
duration of inotropes in ICU, (inotrope score), duration of ICU stay, NT proBNP
levels before induction and 24 h postoperatively, creatine kinase-MB levels in
the immediate postoperative, first and second day. RESULTS: Mean heart rate was
significantly higher in propofol group during sternotomy, (P = 0.021). Propofol
group had a significantly more number of patients requiring nitroglycerine in the
prebypass period (P = 0.01). The increase in NT proBNP from preoperative to
postoperative value was lesser in the isoflurane group compared to propofol even
though the difference was not statistically significant. The requirement of
phenylephrine to maintain mean arterial pressure within 20% of baseline,
mechanical ventilation duration, inotrope use, duration of ICU stay and hospital
stay were found to be similar in both groups. CONCLUSION: Propofol exhibit
comparable myocardial protective effect like that of isoflurane in patients
undergoing coronary artery bypass graft surgery. Considering the unproven
mortality benefit of isoflurane and the improved awareness of green OT concept,
propofol may be the ideal alternative to volatile anesthetics, at least in
patients with good left ventricular function.
PMID- 29336391
TI - Design and standardization of tools for assessing the perceived heart risk and
heart health literacy in Iran.
AB - OBJECTIVES: The aim is to achieve the standard tools for heart health, the
present study aimed to design, develop, and standardize the two questionnaires of
perceived heart risk scale (PHRS) and heart health literacy scale (HHLS).
METHODS: The present study was a methodological research conducted on the
residents of Kermanshah Province, Iran, using the multi-stage cluster sampling.
Further, considering the scientific methods in the psychometric field, the design
of the research questionnaires was conducted. In addition, the viewpoints of
experts in different domains were qualitatively and quantitatively included to
assess the validity of the questionnaires. To assess the reliability of the
questionnaires, a sample including 31 subjects was first selected and studied
within a fortnight's interval. Then, the reliability and validity of the scales
were assessed using factor analysis and Cronbach's alpha in a sample of 771
subjects. RESULTS: After reviewing the viewpoints of experts, the items were
adjusted and implemented in the first sample at two stages. The results were
indicative of the stability and acceptability of the Cronbach's alpha. In
addition, the validity and reliability of the questionnaires were confirmed in
the second sample too. CONCLUSION: According to the results of the present study,
it can be concluded that the two questionnaires of PHRS and HHLS had acceptable
reliability and validity.
PMID- 29336392
TI - Transesophageal echocardiography evaluation of the aortic arch branches.
AB - Visualization of aortic arch branches by transesophageal echocardiography has
been technically challenging. Visualizing these vessels helps in identifying the
extent of dissection of the aorta, assessing the severity of carotid artery
stenosis, presence of atheromatous plaques, patency of the left internal mammary
artery graft, confirmation of subclavian artery cannulation, confirming
holodiastolic flow reversal in the left subclavian artery by spectral Doppler
imaging in case of severe aortic regurgitation, and confirming the optimal
position of the intraaortic balloon perioperatively. The information obtained is
helpful for diagnosis, monitoring, and decision-making during aortic surgery.
PMID- 29336394
TI - Commentary: Similar philosophy does not always synchronize.
PMID- 29336393
TI - Cardiac surgery in a patient with implanted vagal nerve stimulator.
AB - The prevalence of epilepsy worldwide is around 0.5%-2% of the population.
Antiepileptic medications are the first line of treatment in most of the cases
but approximately 25%-30% epilepsy patients are refractory to the single or
combination therapy. The surgical option for temporal lobe epilepsy is temporal
lobectomy, which has its inherent risk of neurological deficits after the
surgery. Patients who are either refractory to combination therapy or do not want
surgical temporal lobectomy are the candidates for electrical stimulation
therapy. Refractory cases require implantable device such as vagal nerve
stimulator (VNS). We are reporting perioperative management of a patient, with an
implanted VNS, posted for pericardiectomy. It is important for the
anesthesiologist to be familiar with the mechanism of VNS for proper
perioperative care.
PMID- 29336395
TI - Tricuspid valve straddling: An uncommon cause of left ventricular outflow tract
obstruction in transposition of great artery with ventricular septal defect.
AB - Transposition of great arteries (TGA) can be associated with left ventricle
outflow tract (LVOT) obstruction. In the presence of ventricular septal defect
(VSD), septal leaflet of tricuspid valve may prolapse through perimembranous VSD
or rarely tricuspid valve tissue may override to produce LVOT obstruction.
Occasionally, this may be mistaken for vegetation due to associated pulmonary
valve endocarditis. We report a case of d-TGA with presumptive pulmonary valve
endocarditis and LVOT obstruction that was found to be due to tricuspid valve
straddling on transesophageal echocardiography, resulting in change in the
surgical plan and thus avoiding catastrophe.
PMID- 29336396
TI - Right atrial fibroma in an adult patient.
AB - Left atrial fibroma as a benign tumor is an exceedingly rare left atrial mass. It
has various clinical signs and symptoms and sometimes leads to serious
complications such as lethal arrhythmia and death. We report a case of right
atrial fibroma in a 40-year-old male who presented with dyspnea and atrial
fibrillation. Transthoracic echocardiography revealed a large sessile mass
attached to interatrial septum near the coronary sinus valve in the right atrium.
The patient underwent surgical resection of tumor through the right atrium. The
postoperative course was unremarkable. Histopathological examination showed that
it was a fibroma. The 6-month follow-up revealed that the patient was in well
condition with no evidence of tumor recurrence.
PMID- 29336397
TI - Large inferolateral left ventricular aneurysm.
AB - The majority of cardiac left ventricular aneurysms involve the anterior and/or
apical wall. We present a case of a 50-year-old man with heart failure caused by
a large inferolateral left ventricular aneurysm and associated mitral
regurgitation, managed by aneurysmectomy, mitral valvuloplasty, and surgical
revascularization.
PMID- 29336398
TI - Concomitant neurogenic and vascular thoracic outlet syndrome due to multiple
exostoses.
AB - We report a rare case of multiple hereditary exostosis where patient presented
with bilateral base of neck exostoses with concurrent compression of brachial
plexus and subclavian artery and vein. The patient was a young 26-year-old woman
with chief complaints of pain in the left upper extremity, paresthesia in the
left ring and little finger, and weakness in hand movement and grip. On referral,
history, physical examination, radiological imaging, and electrodiagnostic tests
evaluated the patient. Due to severe pain and disability in performing routine
activities, surgical intervention was necessary. In the current case, the patient
had thoracic outlet syndrome with concomitant venous, arterial, and neurogenic
sub types. Radial pulse returned and pain associated with brachial plexus
compression was resolved after the surgery.
PMID- 29336399
TI - Commentary: Comments on thoracic outlet syndrome.
PMID- 29336400
TI - Successful resolution with apixaban of a massive left atrial appendage thrombus
due to nonrheumatic atrial fibrillation: A case report and review.
AB - A 32-year-old woman with a past medical history of paroxysmal atrial
fibrillation, long QT syndrome, and implantation of an automatic iimplantable
cardioverter-defibrillator (AICD) following cardiac arrest presented with
disabling symptoms of paroxysmal atrial fibrillation due to recurrent AICD
shocks. Before curative ablation, transesophageal echocardiography was performed
to assess for existing thrombi. This is a rare case of successful resolution with
apixaban of a massive left atrial appendage thrombus due to non-rheumatic atrial
fibrillation that was successfully treated with apixaban.
PMID- 29336401
TI - Bleeding in the lung complicates a routine intracardiac repair: What went
wrong!!!
AB - Cyanotic congenital heart disease presents an increased tendency to bleed in view
of subtle coagulation defects. Airway bleeding can be particularly difficult to
manage while maintaining an adequate ventilation. An isolated lung bleed with the
exclusion of possible traumatic, medical and surgical causes of bleeding, should
alert the attending anesthesiologist to the possibility of the collateral-related
bleeding. Preoperative coil embolization remains an important initial management
step in a case of tetralogy of Fallot (TOF) with major aortopulmonary
collaterals. Nevertheless, the coiling of the collaterals in certain specific
case scenarios is not feasible, rendering the management of a lung bleed, all the
more challenging. We, hereby discuss a case of a 7-year-old girl with a massive
endotracheal bleed at the time of weaning from cardiopulmonary bypass after
corrective surgery for TOF. The subsequent approach and management are discussed.
The optimal management of tetralogy with collaterals mandates an effective
communication among the cardiologist, radiologist, anesthesiologist, and the
surgeon.
PMID- 29336402
TI - Mechanical discordance between left atrium and left atrial appendage.
AB - During standard transesophageal echocardiographic examinations in sinus rhythm
(SR) patients, the left atrial appendage (LAA) is not routinely assessed with
Doppler. Despite having a SR, it is still possible to have irregular activity in
the LAA. This situation is even more important for SR patients where assessment
of the left atrium is often foregone. We describe a case where we encountered
this situation and briefly review how to assess the left atrium and its appendage
in such a case scenario.
PMID- 29336403
TI - Superior vena cava clamping during thoracic surgery: Implications for the
anesthesiologist.
AB - Resection and reconstruction of the SVC is a challenging Intraoperative situation
owing to the potential complications after clamping a patent vessel. Hemodynamic
imbalance and neurological effects of SVC clamping can be life threatening. These
complications can be prevented by careful intraoperative monitoring and
management. Anaesthesiologist must be aware of different options to manage such
challenging situations.
PMID- 29336404
TI - Role of transesophageal echocardiography during left atrial appendage occlusion
device closure in a patient with non-valvular atrial fibrillation and
angiodysplasia of the colon.
AB - Atrial fibrillation is the most common arrhythmia associated with significant
mortality and morbidity secondary to thrombo-embolism. To prevent this thrombo
embolism oral anticoagulation therapy is the recommended treatment. In patients
with contraindications to oral anticoagulation therapy, percutaneous left atrial
appendage occlusion device is indicated. TEE is essential to guide in all the
stages of LAA device deployment. Right from pre-procedure screening, to guiding
during deployment, to rule out any complications and post-procedure surveillance
and monitoring long term outcomes.
PMID- 29336405
TI - Looking inside the third generation left ventricular assist device using color
doppler transesophageal echocardiography.
AB - HeartWare is a third-generation continuous flow left ventricular assist device
(LVAD) and generates centrifugal pattern of blood flow. In the perioperative
setting, interrogating the HeartWare devices is very difficult due to the
interference of the Doppler by the impeller frequency and generation of the
waterfall artifact. We present a case where using color Doppler a view "inside"
the impeller can be seen which corresponds to the centrifugal flow of blood. With
time, these images can be looked into in pathological states such as pump
thrombosis, to come to a more meaningful conclusion regarding the flow of blood
within the centrifugal chamber. Newer technologies are constantly evolving to
give us more meaningful insights into the flow of blood within the heart
chambers. We believe similar technologies can be applied to see the flow of blood
inside the LVAD devices.
PMID- 29336406
TI - Quadricuspid aortic valve: A rare intraoperative diagnosis by transesophageal
echocardiography.
AB - Quadricuspid aortic valve (QAV) is a rare congenital anomaly frequently
associated with other anomalies particularly coronary anomalies. It may be
detected on transthoracic or transesophageal echocardiography. We present here a
case report of a 27-year-old male patient with a QAV, the valve being regurgitant
and requiring aortic valve replacement. It has been reported as isolated case
reports in the literature and various theories exist to the development of QAV.
The diagnosis requires a high degree of suspicion and a detailed assessment, and
if asymptomatic, then patients need to be carefully followed up for the
development of aortic regurgitation.
PMID- 29336407
TI - Unknown left atrial appendage mass! real-time three-dimensional transesophageal
echocardiography helps in identification.
AB - Left Atrial Appendage (LAA) is the most contractile part of Left atrium. It is
also the most frequent place for thrombus formation that may lead to disastrous
consequences. Complete trasoesophageal echocardiography examination always
includes assessing LAA but sometimes unusually placed pectinate muscle, which is
a normal structure may give baffling shadow that can only be interpreted
correctly by Real time 3D echocardiography.
PMID- 29336408
TI - Pneumopericardium after minimally invasive atrial septal defect closure.
AB - Minimally invasive atrial septal defect (ASD) closure is a commonly performed
cardiac surgical procedure and has good outcome. We report an interesting chest X
ray showing pneumopericardium in a patient who underwent ASD closure using a
minimally invasive approach.
PMID- 29336409
TI - Large thymus tumor with invasion into superior vena cava: Transesophageal
echocardiography proved to be helpful during surgery.
PMID- 29336410
TI - Spontaneous coronary artery dissection in anabolic steroid misuse.
PMID- 29336411
TI - Unsolved enigma of atrial myxoma with biventricular dysfunction.
PMID- 29336412
TI - In response to: Unsolved enigma of atrial myxoma with biventricular dysfunction.
AB - Thanks to Raut et al.[1] for appreciating our efforts in managing the case of
biatrial myxomas. A brief discussion is warranted here on the types, size of
cardiac myxomas, interleukin 6 (IL-6) levels, left ventricle (LV) dysfunction,
and their relation. IL-6 is a pleiotropic cytokine with a variety of biologic
activities, including differentiation of B cell, thymocytes, and T cells;
activation of macrophages; and stimulation of hepatocyte to produce acute-phase
proteins such as C-reactive protein.[2],[3] It is also said to have paracrine,
endocrine, and autocrine growth functions.[3].
PMID- 29336413
TI - Erratum: Comparison of the renoprotective effect of dexmedetomidine and dopamine
in high-risk renal patients undergoing cardiac surgery: A double-blind randomized
study.
AB - [This corrects the article DOI: 10.4103/aca.ACA_57_17.].
PMID- 29336414
TI - Reflections about the Impact of Infertility on Female Sexual Function.
PMID- 29336415
TI - Retrospective Study to Determine Stability of Mandibular Setback Surgery using
Bilateral Sagittal Split Osteotomy Technique.
AB - Background Bilateral sagittal split osteototomy of mandible is one of the most
commonly performed orthognathic surgical procedure performed in the mandible.
According to hierarchy of stability, mandibular setback procedure is considered
to be relatively unstable procedure and chances of relapse are higher. Objective
We conducted this study to determine the skeletal stability of mandibular setback
procedure using bilateral sagittal split osteotomy technique in Nepalese
population. Method Lateral cephalograms of 14 patients who underwent mandibular
setback using bilateral saggital split osteotomy were taken pre-operatively (P1),
immediate postoperatively (P2) and eight months to one year post-operatively
(P3). Cephalometric tracing was done for all the cephalograms. Various parameters
of Burstone's hard and soft tissue, Steiner's and McNamara analysis were used in
the study to determine angular and linear changes following surgery. After
tracing the cephalograms, changes between P1- P2, P1-P3 and P2-P3 were
calculated. Mean difference in changes between P1-P2, P1-P3 and P2-P3 were
compared using paired t test. P value less than 0.05 was considered to be
significant. Data analysis was done using SPSS software version 20. Result Mean
setback at Pogonion was 3.03 mm whereas at point B were 4.64 mm. Relapse at
Pogonion was 0.03 mm and relapse at point B were 0.02 mm. Mean change in point A
Nasion-point B angle was 5.1 degrees whereas mean changes in NA-Pogonion angle
were 4.69 degrees. Conclusion There were significant changes in angular as well
as horizontal parameters at P2 but there were no significant changes in those
parameters at P3. This is a preliminary study that we have carried out at our
institution with smaller sample size thus we recommend a study with larger sample
size and long term follow up.
PMID- 29336416
TI - Work Related Musculoskeletal Morbidity among Tailors: A Cross Sectional Study in
a Slum of Kolkata.
AB - Background Musculoskeletal disorders comprise the single largest group of work
related illnesses in developing countries. Sedentary working style with wrong
posture for long time is considered to be an important risk factor, which is
largely modifiable. Objective This study was performed to determine the
prevalence and find out the factors associated with Musculoskeletal disorders
among the workers involved in tailoring occupation. Method A descriptive
community based cross-sectional study was conducted in the urban slums of Chetla,
Kolkata on March and April, 2015. One hundred and ten (110) out of 383 resident
tailors in the area were chosen by simple random sampling and interviewed by
approaching them in their work place. Descriptive statistics and multivariable
logistic regression were used Result Using Nordic Musculoskeletal questionnaire,
Musculoskeletal disorders was found among 65.45% of tailors. The most commonly
affected site was neck (41.8%) followed by lower and upper back. In bivariate
analysis, musculo-skeletal disorders was found to be significantly associated
with age more than 45 years [OR (95% CI)= 3.35 (1.30- 8.60)], working for > 10
years [OR (95% CI)= 7.01 (2.93-16.79)*], working > 8 hours per day [OR (95% CI)=
2.75 (1.20-6.20)], full time job [OR (95% CI)= 2.41 (1.08-5.39)] and unfavourable
workstation ergonomic [OR (95% CI)= 2.40 (1.10-5.40)], whereas in multivariate
analysis age, sex, duration in the profession [AOR (95%CI= 4.40 (1.40- 14.30)],
working hours per day [AOR (95%CI= 7.20 (1.80-27.80)], and unfavourable
workstation ergonomic [AOR (95%CI)= 3.50 (1.26-9.80)] remained significant.
Conclusion A multidimensional approach including appropriate technique in terms
of operators' posture and ergonomically sound workstation are required to avoid
the debilitating effect of Musculoskeletal disorders among the workers.
PMID- 29336417
TI - Compliance and its Determinants Regarding Iron and Folic Acid Supplementation
during Pregnancy in Kathmandu, Nepal.
AB - Background Iron deficiency anemia is one of the major public health problems
mostly affecting pregnant women of developing countries like Nepal. Kathmandu,
the capital city of Nepal, has considerably high prevalence of anemia, which is
attributed to inadequate dietary iron and problems of compliance to iron and
folic acid supplementation. Objective This descriptive study aimed to identify
the levels of and determinants associated with compliance regarding Iron and
folic acid supplementation among pregnant women in Kathmandu, Nepal. Method The
study was conducted in Paropakar Maternity and Women's Hospital in Kathmandu.
Systematic random sampling was done to select a total of 406 samples that were
either handed questionnaire for self-administration or interviewed. The chi2 test
and multiple linear regressions were used for statistical analysis. Result The
findings showed 73.2% of the respondents had high compliance, 12.8% moderate
compliance, and 14% low compliance to iron and folic acid supplementation. More
than half of the respondents had insufficient knowledge regarding anemia, iron
deficiency and iron and folic acid supplementation. Multiple linear regression
revealed that perceived severity, perceived barriers and social support were
determinants of compliance to iron and folic acid supplementation (p<0.05).
Conclusion This study infers that there is a lack of knowledge and awareness
regarding anemia, iron deficiency, and iron and folic acid supplementation among
pregnant women, and improvement in social support and perception of severity of
the disease, and minimization of associated barriers may lead to better outcome
in terms of compliance to iron and folic acid supplementation among pregnant
women.
PMID- 29336418
TI - Dysmenorrhea and Stress among the Nepalese Medical Students.
AB - Background Dysmenorrhea is the most common gynecological disorder in women of
reproductive age with implications as reduced quality of life and school
absenteeism. Mental stress is possibly the most important known predisposing
factor for primary dysmenorrhea. Objective This study aims to assess the
relationship between stress and dysmenorrhea amongst the Nepalese medical
students. Method This is cross-sectional descriptive study, conducted from 1st
Dec. 2012 to 31st Jan. 2013. The study was conducted in Kathmandu University
School of Medical Sciences. A total of 184 participants consented for this study
and each one was given a questionnaire to complete. This study included only
unmarried nulliparous, healthy (all through first to final years) female medical
students, in age group of 16 to 24 years. Result The mean age of the participants
was 19.43(+/-3.9) years. Among them, 67% of the participants experienced
dysmenorrhea. Of them, 85% experienced increase in frequency and severity of
dysmenorrhea after joining medical college. Similarly, 65% of participants
considered medical education to be stressful. Of participants experiencing
dysmenorrhea, 29.45% missed classes and 17.39% participants had positive family
history of dysmenorrhea in first and second degree relatives. Conclusion The
present study indicated a positive relationship between psychological stress and
dysmenorrhea. Dysmenorrhea is the leading cause of recurrent short-term school
absence in young ladies; this issue certainly needs to be addressed.
PMID- 29336419
TI - Variable Presentations of Sinonasal Polypoid Masses: A Tertiary Institution
Experience.
AB - Background Lesions of the sinonasal area are varied, but they mostly present as
polypoid masses which require meticulous work-up to reach at the most probable
diagnosis. Objective Analysis of polypoid sinonasal masses in terms of etiology,
clinical presentations, brief demographic profile, clinico-histologic correlate
where possible, and follow-up results. Method In this descriptive, longitudinal
study, 198 patients with polypoid sinonasal masses attending the otolaryngology
clinic of a tertiary teaching institute were selected using proper selection
criteria and analyzed through a pre-set proforma and algorithm for a diagnostic
work-up (that included histopathology where necessary). Result Common
presentations were nasal obstruction (~89%), discharge (~70%) and hyposmia
(~22%). Though nearly 87% was clinically benign and 8% indeterminate, therapeutic
and diagnostic interventions (including histopathology) showed 91% truly benign,
of which polyposis formed the bulk. Sensitivity of clinical detection was 75% for
benign lesions and 62% for malignancies. Diagnosis depended on histopathology in
52.52% cases, including the clinically malignant, the "grey zone", and more than
40% of the clinically benign lesions. There was male predilection (2.16 for
benign lesions and 1.57 for malignant), rural preponderance, and above 60% of the
patients were within 50-70 years. There was ~26% recurrence in the follow-up
period of a minimum of one year, predominantly in polyposis (29.55%) and
malignancies (~39%). Conclusion Presentations of polypoid sinonasal masses are
variable, etiology of which is mostly benign. Proper clinico-histologic correlate
is necessary for correct diagnosis. A low threshold of suspicion is required
because of this variability, necessitating follow-up for further evaluation.
PMID- 29336420
TI - Perception on Informed Consent Regarding Nursing Care Practices in a Tertiary
Care Center.
AB - Background Consent for care procedures is mandatory after receipt of adequate
information. It maintains patient's rights and autonomy to make thoughtful
decisions. Poor communication often leads to poor health quality. Objective To
assess hospitalized patients' perception on informed consent regarding nursing
care practices in a tertiary care center. Method This is a descriptive cross
sectional study among 113 admitted patients conducted in February 2012 at
Dhulikhel Hospital, Nepal. Patients of various wards were selected using
purposive non-probability sampling with at least 3 days of hospitalization. Close
ended structured questionnaire was used to assess patients' perception on three
different areas of informed consent (information giving, opportunity to make
decision and taking prior consent). Result Among the participants 71.6% perceived
positively regarding informed consent towards nursing care practices with a mean
score of 3.32 +/- 1.28. Patients' perception on various areas of informed consent
viz. information giving, opportunities to make specific decision and taking prior
consent were all positive with mean values of 3.43+/-1.12, 2.88+/-1.23, 3.65+/
1.49 respectively. Comparison of mean perception of informed consent with various
variables revealed insignificant correlation (p-value >0.05) for age, educational
level and previous hospitalization while it was significant (p-value < 0.05) for
communication skills of nurses. Conclusion Majority of patients have positive
perception on informed consent towards nursing care practices. Communication
skills of nurses affect the perception of patients' regardless of age, education
level and past experiences.
PMID- 29336421
TI - Reflux Symptom Index and Reflux Finding Score in Diagnosis of Laryngopharyngeal
Reflux.
AB - Background Although laryngopharyngeal reflux is a common condition encountered in
otolaryngological practice, its diagnosis is not very easy because of its
indistinct symptoms Objective To assess the efficacy of proton pump inhibitors
versus proton pump inhibitors with lifestyle modification in patients with
laryngopharyngeal reflux. Method Prospective, analytical study conducted in
Department of Otorhinolaryngology and Head and Neck Surgery at Dhulikhel
Hospital, Kathmandu University Hospital between January 2015 to January 2016.
Eighty two patients with laryngopharyngeal reflux having Reflux symptom index >
13 and Reflux finding score > 7 were included. Patients were divided into 2
groups. Group A comprised of patients treated with proton pump inhibitors alone
and Group B with Proton pump inhibitors with lifestyle modification. Pre and post
therapeutic reflux finding score and reflux symptom index were compared. Result
The mean reflux symptom index score difference before and after treatment in
group A was 16.70 and group B was 14.58. Similarly, mean reflux finding score
difference before and after treatment in group A was 8.68 and group B was 9.92.
Comparison of reflux finding score and reflux symptom index scores before and
after treatment revealed improvement in both groups and the difference was
statistically significant (p<0.001). However, comparison of pre and post
therapeutic and scores between group A and B, showed no statistical significance.
Conclusion The extent of symptomatic improvement correlated positively with both
proton pump inhibitor therapy alone as well as with proton pump inhibitor therapy
along with lifestyle modification. Although addition of lifestyle modification
offered incremental benefit for treating laryngopharyngeal reflux, it was not
found to be statistically significant.
PMID- 29336422
TI - Cold Pressor Test in Borderline Hypertensive University Students.
AB - Background Hyperactive sympathetic reaction is an important factor for
development of hypertension in young individuals. The stress induced increase in
blood pressure recovers within very short period of time and those with
exaggerated stress induced cardiovascular response at young age have a high risk
of blood pressure elevation in future. Objective To determine the cardiovascular
reactivity in response to cold and to correlate its relation with factors such as
smoking, family history and physical activity. Method Study was conducted in the
Department of Pharmacy, Kathmandu University from July to November, 2015. Resting
blood pressure was recorded using sphygmomanometer in sitting position after 5
minutes of rest. Out of 130 volunteers, 34 were found to be prehypertensive and
equal number of normotensive were recruited randomly to perform the test. The
subjects were directed to immerse his/her right hand up to the wrist in cold
water of 10C for 1 minute. The blood pressure was recorded just before the hand
was taken out of the water and then 1.5 minutes and 4 minutes after the
withdrawal. Data was analyzed by Student's t test using Microsoft Excel 2007.
Result Systolic and diastolic blood pressure increased significantly after cold
pressor test in both normal (systolic blood pressure from 110+/-6.46 to 119+/
9.45 mmHg and diastolic blood pressure from 71+/-4.63 to 78+/-6.15 mmHg) and
prehypertensive group (systolic blood pressure from 122+/-6.75 to 126+/-8.05 mmHg
and diastolic blood pressure from 79+/-6.78 to 85+/-7.76 mmHg). Maximum recovery
in both systolic and diastolic blood pressure was observed in 2.5 minutes of
removal of hand from cold water. Though sharp drop was observed in blood pressure
at the end of 2.5 minute in both groups of individuals, the recovery in case of
prehypertensive individual was not sharper. In the present study, significant
rise in diastolic blood pressure was observed in prehypertensive smoking males.
Also the difference was significant (p<0.02) in recovery of diastolic blood
pressure between smoker and non smoker prehypertensive group. Conclusion This
study suggests that prolonged elevation in blood pressure in response to stress
in young individual can be used as marker of development of hypertension in
future. Adopting a healthier lifestyle can help to delay the development of
hypertension in later life.
PMID- 29336423
TI - Prevalence of Anatomical Variations of the Sinonasal Region and their
Relationship with Chronic Rhinosinusitis.
AB - Background Precise knowledge of anatomic variations of nose and paranasal sinus
complex is essential for achieving best surgical results during endoscopic sinus
surgery. Computed tomography is the gold standard investigation for evaluation of
paranasal sinuses and adjacent structures. Objective To study prevalence of
anatomical variations of nose, paranasal sinuses and osteomeatal complex and to
identify a probable association between anatomical variations and chronic
rhinosinusitis. Method Prospective, analytical study conducted in 218 patients
with Chronic rhinosinusitis in Department of Radiology, Dhulikhel Hospital,
Kathmandu University Hospital between January 2015 to January 2016. Volumetric
axial CT scan was done in 128 slice CT scanner in 3mm thickness from frontal
sinus to floor of maxillary sinus with thin multiplanar reconstruction.
Radiological findings were reviewed and obtained data analyzed with SPSS version
16. Pearson chi square test and Pearson correlation coefficient were used for
statistical analysis. Result The most common anatomical variation was pneumatized
agger nasi cells followed by concha bullosa and deviated nasal septum
respectively. Statistical significance were seen between ipsilateral agger nasi
cell and frontal sinusitis (p< 0.001), ipsilateral haller cell and concha bullosa
with maxillary sinusitis (p<0.001) and onodi cell with sphenoid sinusitis
(p<0.001), However, no obvious statistical correlation was noted between deviated
nasal septum with ipsilateral maxillary sinusitis. Conclusion Precise knowledge
of anatomic variations of the paranasal sinuses is important in chronic
rhinosinusitis to prevent possible complications during surgery. Computed
tomography is the modality of choice in evaluation of paranasal sinuses and
adjacent structures.
PMID- 29336425
TI - Multi-Detector Computed Tomography Evaluation of Normal Appendix.
AB - Background Appendix is a blind-ended tubular structure arising from caecum, with
variable intraluminal contents and position. Acute appendicitis is one of the
common indications for emergency radiological investigation. Objective To assess
visualization rate, size and position of normal appendix by Computed Tomography
(CT). Method This cross-sectional observational study was done in 198 individuals
undergoing abdominal CT without suspicion of acute appendicitis and without any
pathology localized within right iliac fossa. Axial and coronal reformatted
images of nonenhanced and contrast enhanced CT of abdomen were evaluated for
visualization of appendix. Visualized appendices arising from caecum were traced
and tip localized. Contents within the appendicular lumen were also evaluated and
maximum transverse diameter of appendix measured. The relationship between
appendicular diameter, intraluminal content and position with different age
groups & gender were also derived. Result Visualization rates of appendix were
90% (93% male and 87% female) in nonenhanced CT and 97% (99.8% male and 95.4%
female) in enhanced CT. The mean diameter of the appendix was 6.2 +/- 1.16 mm.
Most common location of the tip of appendix was pelvic position, followed by
retrocaecal position. Most of the appendices showed intraluminal air. Conclusion
Multi-Detector Computed Tomography is superior over ultrasonography (USG) in
detection of appendix. Modifications of CT protocol reduce limitations of CT over
ultrasound in evaluation of appendix. Ultrasound size criteria for appendicitis
(>6 mm) is not applicable in CT as normal appendix can measure >6 mm in CT.
PMID- 29336424
TI - Clinical Profile and Electroencephalogram Findings in Children with Seizure
Presenting to Dhulikhel Hospital.
AB - Background Seizure disorder is the most common childhood neurologic condition and
a major public health concern. Identification of the underlying seizure etiology
helps to identify appropriate treatment options and the prognosis for the child.
Objective This study was conducted to investigate the clinical profile, causes
and electroencephalogram findings in children with seizure presenting to a
tertiary center in Kavre district. Method This was a hospital based prospective
study carried out in the Department of Pediatrics, Dhulikhel Hospital, Kavre from
1st April 2015 to 31st March 2016. Variables collected were demographics,
clinical presentations, laboratory tests, brain imaging studies,
electroencephalography, diagnosis and outcome. Result Study included 120 (age 1
month to 16 years) children attending Dhulikhel Hospital. Majority of the
patients were male (60.84%). Age at first seizure was less than 5 years in 75.83%
of children. Seizure was generalized in 62.50%, focal in 31.67% and unclassified
in 5.83%. Common causes of seizure were - Primary generalized epilepsy (26.66%),
neurocysticercosis (10%) and hypoxic injury (6.6%) which was diagnosed in the
perinatal period. Febrile seizure (26.66%) was the most common cause of seizure
in children between 6 months to 5 years of age. Neurological examination,
electroencephalography and Computed Tomography were abnormal in 71.66%, 68.92%
and 58.14% cases respectively. Seizure was controlled by monotherapy in 69.16%
cases and was resistant in 7.50% of the cases. Conclusion Primary generalized
epilepsy and febrile seizure were the most common causes of seizures in children
attending Dhulikhel Hospital. Electroencephalogram findings help to know the
pattern of neuronal activity. Response to monotherapy was good and valproic acid
was the most commonly used drug.
PMID- 29336426
TI - Combination Topical PUVAsol with Methotrexate Versus Methotrexate in the
Treatment of Palmoplantar Psoriasis.
AB - Background Non-pustular palmoplantar psoriasis (PPP) is chronic and disabling
dermatosis. Topical psoralen and solar ultraviolet - A therapy (PUVAsol) is
efficacious and safe therapy in psoriasis management. Objective To study the
efficacy and adverse clinical effect profile of topical PUVAsol along with
methotrexate in PPP. Method This is a prospective, randomized, clinical trial
conducted among 54 patients with moderate to severe PPP. Patients were grouped
into two categories. Group I was treated with weekly oral methotrexate only while
group II had additional soak PUVAsol therapy twice weekly for a total of three
months. Modified palmoplantar psoriasis area severity index (mPPPASI) score was
used for quantification of severity. Patients were followed up monthly for the
efficacy and adverse clinical event profile for 3 months; additionally patients
were followed up monthly for next three months for assessment of relapse. Result
The mean age of patients with PPP was found to be 38.7 +/- 13 years and male:
female ratio was 1.1:1. In comparison to group I patients, statistically
significant improvement was observed among group II patients in the third month
follow up (p= 0.039). Fifteen patients (35%) achieved mPPPASI 75 during the
treatment period. No significant difference was noted among the mPPPASI score
during relapse assessment. Eleven (29%) patients had evidence of relapse (mPPPASI
more than 25% of baseline) during follow up period. No statistically significant
adverse clinical events were noted. Conclusion Topical PUVAsol is an efficacious,
safe and cost effective modality in moderate to severe PPP. It could be employed
in rotational or maintenance therapy of psoriasis.
PMID- 29336427
TI - Congenital Bilateral Coloboma of Upper Eyelid.
AB - Congenital coloboma of eyelid is a rare anomaly. There is partial or total
absence of eyelid structures. A seven year male child had coloboma of both the
upper lids lateral to lacrimal puctum affecting the medial half of lid
symmetrically with symblepharon in region of defect bilaterally. The study was
carried out at Maharaja Krushna Chandra Gajpati Medical College Berhampur, Odisha
in year 2010. Both eyebrows were abnormal. He presented on and off diminution of
vision, burning sensation, redness and watering from both the eyes on and off. On
examination high refractive error was detected (visual aquity was 6/18 in
righteye and 6/24 in left eye). Cornea was dry and opacities were present in both
the eyes. There was limitation of ocular movement in both sides due to
symblepharon. Nystagmus was present. The subject did not have any other
associated anomaly. The birth and family history was normal. This case can be
surgically treated and earliest management can give good fuctional as well as
cosmetic results.
PMID- 29336428
TI - Keratocystic Odontogenic Tumour Mimicking Lateral Periodontal Cyst: A Diagnostic
Dilemma.
AB - The Keratocystic Odontogenic Tumor is a developmental cyst derived from the
enamel organ or from the dental lamina. It is a benign, multicystic, intraosseous
tumor of odontogenic origin, with a characteristic lining of parakeratinized
stratified squamous epithelium and has a potential for aggressive, infiltrative
behavior and recurrence. Keratocystic Odontogenic Tumors have a predilection for
males and occurs mainly in the second and third decade of life, most commonly in
the mandible, mostly in the posterior body, the angle and the ascending ramus. It
extends in the intramedullary space making it difficult to diagnose at an early
stage. It is regarded as a distinctive entity because of its characteristic
histology, proliferation kinetics and behavior. Main in 1970 described,
collateral variant of Keratocystic Odontogenic Tumor, which presents adjacent to
the roots of the teeth usually in the mandibular premolar region and
radiologically is indistinguishable from the lateral periodontal cyst and
gingival cyst.
PMID- 29336429
TI - Thyroid Isthmus Agenesis in a Patient with Papillary Carcinoma of Thyroid.
AB - Thyroid gland is the largest of all endocrine glands. It is composed of two
lobes. These two lobes are joined by an isthmus and this resemble the letter "H".
A wide range of morphological variations and developmental anomalies of the
thyroid gland like hypoplasia, ectopy, hemiagenesis, and agenesis have been
reported in literature. Out of these, the incidence of agenesis of the thyroid
isthmus is rare, and very few cases have been reported. In our report, 28 year
old male patient was found with agenesis of thyroid isthmus with papillary
carcinoma in the right lobe of thyroid. During the operation it was seen that the
right and left thyroid lobes were independent from each other and isthmus was
absent. We will present a case of thyroid isthmus agenesis and discuss the
clinical importance and the incidence of this case.
PMID- 29336430
TI - Persistent Trophoblastic Disease at Cesarean Scar.
AB - Pregnancy over the cesarean scar is the rarest cause of ectopic pregnancy and
development of persistent trophoblastic disease at the scar site is extremely
rare. A high index of suspicion is needed for early diagnosis and management of
cesarean scar molar pregnancy. This condition is difficult to diagnose and must
be considered in the patient with a history of cesarean section who has
persistent vaginal bleeding or symptoms of pregnancy after suction evacuation.
Diagnosis can be confirmedby measuring beta Human Chorionic Gonadotropin levels,
transvaginal ultrasound with doppler flow evaluation. As this is an uncommon
condition, this case report with conservative non surgical approach will add up
to its clinical spectrum.
PMID- 29336431
TI - Anti-PD1 in the wonder-gut-land.
AB - After the initial success of cancer immunotherapy using immune checkpoint
blockers, the challenge is to understand why only a minority of patients respond
to the therapy and to increase the rate of response. Three recent papers now
report that the gut microbiota modulates the response to anti-PD1 therapy in
patients with epithelial cancers or melanoma.
PMID- 29336432
TI - Increased Mortality Rates With Prolonged Corticosteroid Therapy When Compared
With Antitumor Necrosis Factor-alpha-Directed Therapy for Inflammatory Bowel
Disease.
AB - OBJECTIVES: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory
bowel diseases (IBD) that compromise quality of life and may increase mortality.
This study compared the mortality risk with prolonged corticosteroid use vs.
antitumor necrosis factor-alpha (anti-TNF) drugs in IBD. METHODS: A retrospective
cohort study was conducted among Medicaid and Medicare beneficiaries from 2001 to
2013 with IBD prescribed either >3,000 mg of prednisone or equivalent within a 12
month period or new initiation of anti-TNF therapy, each treated as time-updating
exposures. The primary outcome was all-cause mortality. Secondary outcomes
included common causes of death. Marginal structural models were used to
determine odds ratios (ORs) and 95% confidence intervals (CIs) for anti-TNF use
relative to corticosteroids. RESULTS: Among patients with CD, 7,694 entered the
cohort as prolonged corticosteroid users and 1,879 as new anti-TNF users. Among
patients with UC, 3,224 and 459 entered the cohort as prolonged CS users and new
anti-TNF users, respectively. The risk of death was statistically significantly
lower in patients treated with anti-TNF therapy for CD (21.4 vs. 30.1 per 1,000
person-years, OR 0.78, 0.65-0.93) but not for UC (23.0 vs. 30.9 per 1,000 person
years, OR 0.87, 0.63-1.22). Among the CD cohort, anti-TNF therapy was also
associated with lower rates of major adverse cardiovascular events (OR 0.68, 0.55
0.85) and hip fracture (OR 0.54, 0.34-0.83). CONCLUSIONS: Compared with prolonged
corticosteroid exposure, anti-TNF drug use was associated with reduced mortality
in patients with CD that may be explained by lower rates of major adverse
cardiovascular events and hip fracture.
PMID- 29336433
TI - Eosinophilic Esophagitis: Relationship of Subepithelial Eosinophilic Inflammation
With Epithelial Histology, Endoscopy, Blood Eosinophils, and Symptoms.
AB - OBJECTIVES: For technical reasons, the histologic characterization of
eosinophilic esophagitis (EoE)-specific alterations is almost exclusively based
on those found in the esophageal epithelium, whereas little is known about
subepithelial abnormalities. In this study, we aimed to systematically assess the
nature of subepithelial histologic alterations, and analyze their relationship
with epithelial histologic findings, endoscopic features, and symptoms. METHODS:
Adult patients with established EoE diagnosis were prospectively included during
a yearly follow-up visit. Patients underwent assessment of clinical, endoscopic,
and histologic disease activity using EoE-specific scores. RESULTS: We included
200 EoE patients (mean age 43.5+/-15.7 years, 74% males) with a median peak count
of 36 intraepithelial eosinophils/hpf (IQR 14-84). The following histologic
features were identified in the subepithelial layer: eosinophilic infiltration
(median peak count of 20 eosinophils/hpf (IQR 10-51)), eosinophil degranulation
(43%), fibrosis (82%), and lymphoid follicles (56%). Peak intraepithelial
eosinophil counts were higher, identical, and lower when compared to the
subepithelial layer in 62.5%, 7%, and 30.5% of patients, respectively. Anti
eosinophilic treatment at inclusion did not influence the relation between
subepithelial and epithelial peak eosinophil counts. Subepithelial histologic
activity correlated with epithelial histologic activity (rho 0.331, P<0.001),
endoscopic severity (rho 0.208, P=0.003), and symptom severity (rho 0.179,
P=0.011). Forty percent (21/52) of patients with <15 intraepithelial
eosinophils/hpf had subepithelial peak counts of >=15/hpf. CONCLUSIONS: There is
a significant but modest correlation between subepithelial histologic activity
and epithelial histologic activity, endoscopic severity, and symptom severity.
The long-term clinical impact of assessing subepithelial alterations in EoE needs
to be further elucidated.
PMID- 29336435
TI - Cardiac regeneration in 2017: Novel paradigms in the fight against heart failure.
PMID- 29336436
TI - Dyslipidaemias in 2017: Atherogenic lipoproteins as treatment targets.
PMID- 29336437
TI - Ge12{Fe(CO)3}8(MU-I)4: a germanium-iron cluster with Ge4, Ge2 and Ge units.
AB - The germanium-iron cluster Ge12{Fe(CO)3}8(MU-I)4 was prepared by reacting GeI4
and Fe2(CO)9 in [BMIm]Cl/AlCl3 as ionic liquid (BMIm: 1-butyl-3
methylimidazolium). The cluster contains a Ge12Fe8 metal core consisting of a
central Ge4 rectangle, two Ge2 pairs, and four single Ge atoms. These Ge units
are interconnected by Fe atoms to a real Ge-Fe cluster. According to DFT
calculations, Hund's localization criterion is fulfilled for the whole cluster if
we assume three different atomic charges on the Ge4, Ge2, and Ge units.
PMID- 29336434
TI - ACG Clinical Guideline: Alcoholic Liver Disease.
AB - Alcoholic liver disease (ALD) comprises a clinical-histologic spectrum including
fatty liver, alcoholic hepatitis (AH), and cirrhosis with its complications. Most
patients are diagnosed at advanced stages and data on the prevalence and profile
of patients with early disease are limited. Diagnosis of ALD requires
documentation of chronic heavy alcohol use and exclusion of other causes of liver
disease. Prolonged abstinence is the most effective strategy to prevent disease
progression. AH presents with rapid onset or worsening of jaundice, and in severe
cases may transition to acute on chronic liver failure when the risk for
mortality, depending on the number of extra-hepatic organ failures, may be as
high as 20-50% at 1 month. Corticosteroids provide short-term survival benefit in
about half of treated patients with severe AH and long-term mortality is related
to severity of underlying liver disease and is dependent on abstinence from
alcohol. General measures in patients hospitalized with ALD include inpatient
management of liver disease complications, management of alcohol withdrawal
syndrome, surveillance for infections and early effective antibiotic therapy,
nutritional supplementation, and treatment of the underlying alcohol-use
disorder. Liver transplantation, a definitive treatment option in patients with
advanced alcoholic cirrhosis, may also be considered in selected patients with AH
cases, who do not respond to medical therapy. There is a clinical unmet need to
develop more effective and safer therapies for patients with ALD.
PMID- 29336438
TI - Zein-derived peptides as nanocarriers to increase the water solubility and
stability of lutein.
AB - Zein and its derived peptides have been used as nanocarriers for bioactive
components. Lutein, as well as other xanthophylls, are characterized by blue
light filtering and anti-oxidant properties. However, lutein is unstable and has
low water solubility, poor absorption, and low bioavailability. In order to
protect lutein from oxidative degradation, and to enhance its solubility and
dispersibility, stability and bioactivity, lutein-loaded zein nanoparticles (LLZ
NP) and zein-derived peptide nanoparticles (LLZ-PEP-NP) were prepared by the
solvent diffusion method. Compared to LLZ-NP, LLZ-PEP-NP possessed good
physicochemical properties, including particle size, polydispersity index, zeta
potential, entrapment efficiency and in vitro stability. Specifically,
transmission electron microscopy (TEM) images showed that LLZ-PEP-NP had a
spherical form with a nanometric size and lutein was efficiently loaded into zein
derived peptides through self-assembly. Dynamic light scattering (DLS) results
demonstrated that LLZ-PEP-NP had a narrow size distribution in the range of 200
300 nm and a decreased zeta potential compared to that of LLZ-NP. The lutein
entrapment efficiency (EE%) of LLZ-NP and LLZ-PEP-NP was more than 85%, while LUT
PEP-NP showed higher lutein entrapment efficiency because of the better capacity
of peptides bound with lutein. Nanoencapsulation of lutein into LLZ-PEP-NP
resulted in a significantly higher solubility compared to nanoencapsulation of
lutein into LLZ-NP and free lutein. The stabilities of lutein in zein-derived
peptide nanoparticles in simulated gastric fluid (SGF) and simulated intestinal
fluid (SIF) were improved. These results suggest that zein-derived peptides have
the potential to be used as nanocarriers to enhance the solubility and stability
of lutein, which can further improve its bioavailability.
PMID- 29336439
TI - Tailoring a nanostructured plasmonic absorber for high efficiency surface
assisted laser desorption/ionization.
AB - The surface-assisted laser desorption/ionization (SALDI) effect is investigated
on Au plated anodized aluminum oxide (Au/AAO) thin films, a new type of low-cost
broadband plasmonic absorber, which has attracted a lot of attention recently.
Mass spectrometry (MS) measurements show that the ionization efficiency of Au/AAO
substrates can be significantly improved (*30 fold) by simply tuning the size of
nanopores in Au/AAOs. This leads to a signal-to-noise ratio of 394, which is 4
times better than the result obtained using the conventional matrix-assisted
laser desorption/ionization (MALDI)-MS technique. Experimental and theoretical
studies show that the dramatic improvement is caused by the pore-size-dependent
optical and thermal properties of Au/AAOs. It provides a simple yet effective
strategy for designing and building high performance plasmonic SALDI substrates.
PMID- 29336440
TI - Manganese/cobalt-catalyzed oxidative C(sp3)-H/C(sp3)-H coupling: a route to alpha
tertiary beta-arylethylamines.
AB - Reported herein is an oxidative coupling reaction of an alpha-C(sp3)-H bond of
amine with a benzylic C(sp3)-H bond through Mn or Co catalysis to provide diverse
collections of alpha-tertiary beta-arylethylamines. This protocol features an
easily installed and removable coordinating activation group, a wide scope of
substrates, low-cost metal catalysts, easily available starting materials and
synthetic simplicity.
PMID- 29336441
TI - A high pressure study of calmodulin-ligand interactions using small-angle X-ray
and elastic incoherent neutron scattering.
AB - Calmodulin (CaM) is a Ca2+ sensor and mediates Ca2+ signaling through binding of
numerous target ligands. The binding of ligands by Ca2+-saturated CaM (holo-CaM)
is governed by attractive hydrophobic and electrostatic interactions that are
weakened under high pressure in aqueous solutions. Moreover, the potential
formation of void volumes upon ligand binding creates a further source of
pressure sensitivity. Hence, high pressure is a suitable thermodynamic variable
to probe protein-ligand interactions. In this study, we compare the binding of
two different ligands to holo-CaM as a function of pressure by using X-ray and
neutron scattering techniques. The two ligands are the farnesylated hypervariable
region (HVR) of the K-Ras4B protein, which is a natural binding partner of holo
CaM, and the antagonist trifluoperazine (TFP), which is known to inhibit holo-CaM
activity. From small-angle X-ray scattering experiments performed up to 3000 bar,
we observe a pressure-induced partial unfolding of the free holo-CaM in the
absence of ligands, where the two lobes of the dumbbell-shaped protein are
slightly swelled. In contrast, upon binding TFP, holo-CaM forms a closed globular
conformation, which is pressure stable at least up to 3000 bar. The HVR of K
Ras4B shows a different binding behavior, and the data suggest the dissociation
of the holo-CaM/HVR complex under high pressure, probably due to a less dense
protein contact of the HVR as compared to TFP. The elastic incoherent neutron
scattering experiments corroborate these findings. Below 2000 bar, pressure
induces enhanced atomic fluctuations in both holo-CaM/ligand complexes, but those
of the holo-CaM/HVR complex seem to be larger. Thus, the inhibition of holo-CaM
by TFP is supported by a low-volume ligand binding, albeit this is not associated
with a rigidification of the complex structure on the sub-ns A-scale.
PMID- 29336442
TI - Ambient chemical fixation of CO2 using a highly efficient heterometallic helicate
catalyst system.
AB - Two novel heptanuclear 3d-4f helicates have been synthesized and characterized.
The helicates act as catalysts and show high catalytic activity for the coupling
of CO2 and epoxides to obtain cyclic carbonates with a wide substrate scope at
ambient temperature and pressure.
PMID- 29336443
TI - Actuating and memorizing bilayer hydrogels for a self-deformed shape memory
function.
AB - A general strategy for fabricating a double layer self-deformed shape memory
hydrogel which includes a thermo-responsive actuating layer and a pH-responsive
memorizing layer is presented. Compared with traditional shape memory polymer
systems, the temporary shape of the hydrogel could be generated by a thermo
responsive actuating layer upon the trigger of heat without the need for an
external force, which could be further memorized by the pH-responsive memorizing
layer.
PMID- 29336444
TI - The structural diversity of C-rich DNA aggregates: unusual self-assembly of
beetle-like nanostructures.
AB - We studied the ability of oligonucleotides CnT25 (n = 2, 5, 7, 9, 12, 25) to form
an intermolecular i-motif using circular dichroism, ultra-violet spectroscopy,
nuclear magnetic resonance, high-resolution atomic force microscopy, high
performance liquid chromatography, and molecular dynamics simulations. The
arrangement of single-stranded oligonucleotides in multimer i-motifs was very
unusual: C-tracts of different oligonucleotides followed each other consecutively
in order to fold into a closed intermolecular i-motif core with minimal loops
(one cytidine in a loop spanning over a minor groove, three cytidines in a loop
over a major groove); intact T-tracts protruded from predefined loci allowing
visualization of beetle-like nanostructures by atomic force microscopy. The same
structures were formed from analogous biotinylated oligonucleotides demonstrating
one of the potential applications of such structures as carriers of multiple
functional groups. Our findings open up possibilities for the rational design of
pH-sensitive DNA aggregates and evaluation of the efficiency of their assembly.
PMID- 29336445
TI - Single Pd atomic catalyst on Mo2CO2 monolayer (MXene): unusual activity for CO
oxidation by trimolecular Eley-Rideal mechanism.
AB - The geometric stability, electronic structure and catalytic properties of a
single Pd atom deposited on a pristine Mo2CO2 monolayer and a defective Mo2CO2
monolayer with an oxygen vacancy (denoted as Pd/OV-Mo2CO2) are systematically
investigated through density functional theory. We find that the oxygen vacancy
(OV) can stabilize the single Pd atom and make the Pd/OV-Mo2CO2 system an
excellent mono-dispersed atomic catalyst. The Pd dopant serves as an active
center which makes the intermediates react productively around it. Three reaction
mechanisms are considered for CO oxidation to test the catalytic activity of
Pd/OV-Mo2CO2, which exhibits high activity for CO oxidation via a tri-molecular
Eley-Rideal (TER) mechanism with a rate-limiting energy barrier of 0.49 eV. The
pre-adsorbed CO molecules on the Pd dopant could transfer electrons to the O2
2pi* orbitals, which would promote O2 molecule activation and induce O-O bond
scission. This work demonstrates that the defective monolayer MXene may serve as
a promising sort of support to fabricate single atomic catalysts (SACs) for CO
oxidation or other reactions, agreeing well with the experimental reports, which
opens up a new avenue for the design and fabrication of SACs of MXene-based
materials.
PMID- 29336446
TI - An elimination/Heck coupling/allylation cascade reaction: synthesis of 2,3
dihydrobenzofurans from allenoate adducts.
AB - A highly regio- and stereoselective Pd-catalyzed cascade reaction of allenoate
adducts has been developed. Various allenoate adducts of phosphine-catalyzed
addition of allenoates are found to be efficient substrates for the preparation
of 2,3-dihydrobenzofuran. It is the first example of allenoate adducts used as
ideal and practical precursors of hard-to-get functionalized 1,3-butadienes for
heterocycle synthesis.
PMID- 29336447
TI - Synthesis of indolizine derivatives containing eight-membered rings via a gold
catalyzed two-fold hydroarylation of diynes.
AB - A gold-catalyzed method for the construction of indolizines with eight-membered
rings has been developed. The reaction proceeded through a two-fold
hydroarylation with indole or pyrrole derivatives containing a 1,6-diyne using a
tri(1-adamantyl)phosphine gold complex as the catalyst, affording 1,8
disubstituted indolizines in moderate to good yields in DCE at 80 degrees C. The
potential usefulness of these indolizines as blue or green OLEDs has been also
disclosed.
PMID- 29336448
TI - Determination of derived volumetric properties and heat capacities at high
pressures using two density scaling based equations of state. Application to
dipentaerythritol hexa(3,5,5-trimethylhexanoate).
AB - Reliable equations of state (EoS) together with heat capacities at atmospheric
pressure make it possible to determine properties such as the isobaric thermal
expansivity, compressibility, both isothermal and isentropic, high pressure
isobaric heat capacities or speed of sound. In this work, we analysed the
reliability of two density scaling based EoS, Power-Law Density Scaling (PLDS)
and General Density Scaling (GDS), and the Tammann-Tait EoS to determine these
quantities. For this aim, dipentaerythritol hexa(3,5,5-trimethylhexanoate),
diPEiC9, was chosen because it has been recently proposed as a candidate to fill
the gap of reference fluids suitable for high pressure viscometer calibration or
their verification. New experimental densities measured between (283.15 and
398.15) K at pressures up to 70 MPa together with isobaric heat capacities
between (282.93 and 399.92) K and thermal conductivities between (283 and 333) K
at 0.1 MPa of diPEiC9 are reported. Literature relative volumes up to 400 MPa for
this compound were also used. The three EoSs give rise to coherent values of the
above properties. The most difficult property to describe is isobaric thermal
expansivity for which the isobaric curves can present minima and/or maxima and
the isotherm curves can cross at different pressures. The loci of the maxima of
the isobaric thermal expansivity in p-T diagrams of the GDS and PLDS EoSs are
very close.
PMID- 29336450
TI - Lithium diamidodihydridoaluminates: bimetallic cooperativity in catalytic
hydroboration and metallation applications.
AB - Cooperativity between the Li and Al centres is implicated in catalytic
hydroboration reactions of aldehydes and ketones with pinacolborane via
heteroleptic lithium diamidodihydridoaluminates. In addition to implementing
hydroalumination, these versatile heteroleptic ates can also perform as amido
bases as illustrated with an acidic triazole.
PMID- 29336449
TI - pH-Dependent cooperativity and existence of a dry molten globule in the folding
of a miniprotein BBL.
AB - Solution pH plays an important role in protein dynamics, stability, and folding;
however, detailed mechanisms remain poorly understood. Here we use continuous
constant pH molecular dynamics in explicit solvent with pH replica exchange to
describe the pH profile of the folding cooperativity of a miniprotein BBL, which
has drawn intense debate in the past. Our data reconciled the two opposing
hypotheses (downhill vs. two-state) and uncovered a sparsely populated unfolding
intermediate. As pH is lowered from 7 to 5, the folding barrier vanishes. As pH
continues to decrease, the unfolding barrier lowers and denaturation is triggered
by the protonation of Asp162, consistent with experimental evidence.
Interestingly, unfolding proceeded via an intermediate, with intact secondary
structure and a compact, unlocked hydrophobic core shielded from solvent, lending
support to the recent hypothesis of a universal dry molten globule in protein
folding. Our work demonstrates that constant pH molecular dynamics is a unique
tool for testing this and other hypotheses to advance the knowledge in protein
dynamics, stability, and folding.
PMID- 29336451
TI - The uptake, retention and clearance of drug-loaded dendrimer nanoparticles in
astrocytes - electrophysiological quantification.
AB - Nanoparticle-based drug delivery systems may impose risks to patients due to
potential toxicity associated with a lack of clearance from cells or prolonged
carrier-cell retention. This work evaluates vesicular cell uptake, retention and
the possible transfer of endocytosed methylprednisolone-loaded
carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles (NPs) into
secretory vesicles of rat cultured astrocytes. The cells were incubated with NPs
and unitary vesicle fusions/fissions with the plasma membrane were monitored
employing high-resolution membrane capacitance measurements. In the NP-treated
cells the frequency of unitary exocytotic events was significantly increased. The
presence of NPs also induces an increase in the size of exocytotic vesicles
interacting with the plasma membrane, which exhibit transient fusion with
prolonged fusion pore dwell-time. Live-cell confocal imaging revealed that once
NPs internalize into endocytotic compartments they remain in the cell for 7 days,
although a significant proportion of these merge with secretory vesicles destined
for exocytosis. Co-localization studies show the route of clearance of NPs from
cells via the exocytotic pathway. These findings bring new insight into the
understanding of the intracellular trafficking and biological interactions of
drug-loaded dendrimer NPs targeting astrocytes.
PMID- 29336452
TI - Resonant scattering of green light enabled by Ag@TiO2 and its application in a
green light projection screen.
AB - The ability to selectively scatter green light is essential for an RGB
transparent projection display, and this can be achieved by a silver-core,
titania-shell nanostructure (Ag@TiO2), based on the metallic nanoparticle's
localized surface plasmon resonance. The ability to selectively scatter green
light is shown in a theoretical design, in which structural optimization is
included, and is then experimentally verified by characterization of a
transparent film produced by dispersing such nanoparticles in a polymer matrix. A
visual assessesment indicates that a high-quality green image can be clearly
displayed on the transparent film. For completeness, a theoretical design for
selective scattering of red light based on Ag@TiO2 is also shown.
PMID- 29336453
TI - Semimetallic carbon honeycombs: new three-dimensional graphene allotropes with
Dirac cones.
AB - Classic two-dimensional (2D) graphene possesses outstanding properties due to
Dirac cone structures. When scaling up to three-dimensional (3D) structures,
their high porosity and large surface-area-to-volume ratio made them have more
promising engineering perspectives. However, the currently synthesized and
density-functional-theory-predicted 3D graphene structures, termed as carbon
honeycombs (CHCs), are metallic. Herein, we propose new families of stable
semimetallic CHC structures, which have lower energies than the previous
experimentally reported structure and they would be realized experimentally.
Results from density functional theory (DFT) and tight binding (TB) model showed
that multiple Dirac cones with massless Dirac Fermions are present in both
pristine and strained CHCs. Dirac cones in pristine CHCs originated from
interactions between sp2-hybridized carbon atoms along the zigzag direction
(denoted as C, i = alpha, beta,...), while strain-induced direction-dependent
Dirac cones primarily stemmed from interactions (i) between the two C atoms
bonded to a selected sp3-hybridized carbon atom or (ii) between C and C (alpha
carbon atoms at the armchair direction) atoms. The largest Fermi velocity
achieved is 1.204 * 106 m s-1, which is approximately 44.7% larger than that of
graphene. These results open up a new direction in carbon-based 3D porous
materials and these findings provide significant insights on numerous
applications, ranging from nanoelectronics and nanomechanics to gas and liquid
separations.
PMID- 29336455
TI - 5'-Vitamin B12 derivatives suitable for bioconjugation via the amide bond.
AB - Vitamin B12 is an attractive candidate for a drug or an imaging-agent carrier
into cells, due to its dietary uptake and well established transport through
glycoproteins. Utilization of this system requires an appropriate
functionalization of vitamin B12 that both allows for the conjugation of
therapeutics and does not interrupt its recognition by transport proteins.
Modifications at the 5'-position on the ribose moiety are among a few approaches
which meet the criteria. In this article we present vitamin B12 derivatives
bearing either the amino or the carboxylic group at the 5'-position. The presence
of these functional groups enables conjugation of biologically important
molecules to vitamin B12via the amide bond. The established method is not only
limited to organic media but also works in an aqueous environment, giving the
desired products in very good yields.
PMID- 29336454
TI - High temporal resolution delayed analysis of clinical microdialysate streams.
AB - This paper presents the use of tubing to store clinical microdialysis samples for
delayed analysis with high temporal resolution, offering an alternative to
traditional discrete offline microdialysis sampling. Samples stored in this way
were found to be stable for up to 72 days at -80 degrees C. Examples of how this
methodology can be applied to glucose and lactate measurement in a wide range of
in vivo monitoring experiments are presented. This paper presents a general
model, which allows for an informed choice of tubing parameters for a given
storage time and flow rate avoiding high back pressure, which would otherwise
cause the microdialysis probe to leak, while maximising temporal resolution.
PMID- 29336461
TI - New di-anchoring A-pi-D-pi-A configured organic chromophores for DSSC
application: sensitization and co-sensitization studies.
AB - Herein, we report the design and synthesis of three new un-symmetrical metal-free
carbazole based organic dyes, E1-3 with A-pi-D-pi-A architecture, as effective di
anchoring sensitizers in DSSCs. The new entities comprise carbazole as a donor
scaffold connected to three different units, viz. cyano acetic acid, 2,4
thiazolidinedione and barbituric acid as acceptor/anchoring units via vinylene
and phenylene as pi-spacers at 3- and 6-positions of the carbazole ring,
respectively. Photophysical, electrochemical and theoretical studies were carried
out in order to assess their feasibility as active sensitizers. Furthermore,
their photoelectrochemical performances and charge transport properties in
fabricated DSSCs were evaluated. The results revealed that the device fabricated
with the E1 sensitizer displayed the highest PCE of 2.38% among the three dyes.
Its JSC, VOC, and IPCE values were found to be 6.36 mA cm-2, 0.599 V, and 57%,
respectively. Its enhanced performance is attributed to the presence of a highly
electron withdrawing cyano acetic acid unit on either side of the carbazole core
through appropriate pi-spacers. Interestingly, the DFT study indicated that the
electron cloud of the LUMO level has been shifted significantly towards the 2
cyano phenyl acrylic acid connected at the 6th position of the carbazole ring,
when compared to the cyano acrylic acid linked at position 3, confirming
efficient charge separation in E1. The assigned lifetimes of E1-3 obtained from
EIS studies were found to be in accordance with experimentally obtained
photovoltaic parameters. Furthermore, E1-3, when co-sensitized with NCSU-10
sensitizer in DSSCs, displayed higher VOC values, but lower PCE values than that
of NCSU-10.
PMID- 29336462
TI - Cascaded photo-potential in a carbon dot-hematite system driving overall water
splitting under visible light.
AB - Hematite is an earth-abundant and ubiquitous semiconductor with a suitable
bandgap of 2.1 eV for solar water splitting. Unfortunately, it suffers from a low
conduction band position compared to the H+/H2 potential and typically an
external bias has to be applied. Here, we demonstrate carbon dot-hematite (CD
Fe2O3) nanocomposites as photocatalysts for visible-light-driven overall water
splitting without any external bias or scavenger. Notably, the CD-Fe2O3
nanocomposites (carbon dots, 5 wt%) show a hydrogen evolution rate of 0.390 MUmol
h-1 and an oxygen evolution rate of 0.225 MUmol h-1 under visible light
illumination. In our system, carbon dots have been well coupled with hematite and
are detected to generate a photo-induced potential. This photo-potential can be
combined with hematite to meet the requirement for overall water splitting. In
addition, carbon dots can significantly improve the charge separation efficiency.
Our finding may greatly enhance the practical application of hematite for solar
water splitting.
PMID- 29336463
TI - Protein corona in drug delivery for multimodal cancer therapy in vivo.
AB - The protein corona is inevitably formed on nanoparticles (NPs) when they are
introduced in vivo and has been associated with a reduction in targeting yield,
immune recognition and rapid blood clearance, leading to poor tumor accumulation.
We have recently shown that it is possible to exploit the protein corona for drug
delivery by exploiting it for loading and triggering the release of a
photosensitizer Chlorin e6 (Ce6) for simultaneous photodynamic (PDT) and
photothermal therapy (PTT) in vitro. Here, we extended our previous in vitro
studies to evaluate its effectiveness in vivo. Specifically, we pre-formed the
protein corona from mouse serum (MS) around gold nanorods (NRs) and loaded it
with Ce6 to form NR-MS-Ce6. The intravenous delivery of NR-MS-Ce6 at a dose of 10
mg kg-1 Au loaded with 9.63 MUg kg-1 Ce6 into tumor-bearing NCr nude mice
resulted in their tumor accumulation reaching a peak concentration of 560.3 MUg
Au per kg tissue (0.0752% dose) within 6 h post-injection. Subsequent localized
laser irradiation of the xenograft tumor resulted in a significant tumor
temperature increase of 16.85 degrees C within 20 min. Combined with the
simultaneous reactive oxygen species (ROS) production by Ce6 for PDT, complete
tumor regression was achieved within 19 days with no tumor regrowth up to 31
days. Similar to other NPs, significant gold accumulation was observed in the
major reticuloendothelial system (RES) organs, particularly the liver and spleen,
although no acute toxicity was observed histologically 31 days post-treatment.
Our results demonstrated for the first time an in vivo application of the protein
corona around NPs in the loading and delivery of drugs in small animals. The ease
of drug loading and the biocompatibility of the endogenous serum-based protein
corona could make it useful for drug delivery and therapeutic applications
instead of merely being considered as a biological artefact to be eliminated.
PMID- 29336464
TI - Edge orientation dependent nanoscale friction.
AB - Nanoscale friction is generally found to be a function of the contact area.
However, little is known whether and how it is dependent on the contact area
shape. In this study, based on molecular dynamics (MD) simulations about a
rectangular graphene flake sliding on a diamond-supported graphene substrate, we
show that the friction between the flake and the substrate is significantly
dependent on the flake edge oriented perpendicular to the sliding direction, but
less dependent on the edge along the sliding direction. As a result, the friction
between the flake and the substrate is closely related to the aspect ratio of the
flake. We propose a novel nanoscale friction formula for the translational motion
of a rectangular slider. The simulation data fit the formula well and the effect
of the aspect ratio on nanoscale friction can thus be efficiently captured. We
discuss also the origin of the edge orientation dependent nanoscale friction. The
present findings provide not only a preliminary evaluation of the contact area
shape dependent nanoscale friction, but also a quite important guide for modeling
the friction properties of nanodevices based on two-dimensional (2D) materials.
PMID- 29336465
TI - Breast cancer stem-like cells are sensitized to tamoxifen induction of self
renewal inhibition with enforced Let-7c dependent on Wnt blocking.
AB - Let-7 microRNAs have been reported to have tumor suppressive functions; however,
the effect of Let-7 when used in combination with chemotherapies is uncertain,
but may have potential for use in clinical practice. In this study, we used RT
qPCR, western blot analysis, cell proliferation assay, flow cytometry analysis,
immunohistochemistry (IHC) staining, luciferase assays, cell sorting analysis and
xenografted tumor model to explore the role of Let-7 in the chemotherapy
sensitivity of breast cancer stem cells. The findings of the current study
indicated that Let-7 enhances the effects of endocrine therapy potentially by
regulating the self-renewal of cancer stem cells. Let-7c increased the anticancer
functions of tamoxifen and reduced the ratio of cancer stem-like cells (CSCs),
sensitizing cells to therapy-induced repression in an estrogen receptor (ER)
dependent manner. Notably, Let-7 decreased the tumor formation ability of
estrogen-treated breast CSCs in vivo and suppressed Wnt signaling, which further
consolidated the previously hypothesis that Let-7 decreases the self-renewal
ability, contributing to reduced tumor formation ability of stem cells. The
suppressive effects exerted by Let-7 on stem-like cells involved Let-7c/ER/Wnt
signaling, and the functions of Let-7c exerted with tamoxifen were dependent on
ER. Taken together, the findings identified a biochemical and functional link
between Let-7 and endocrine therapy in breast CSCs, which may facilitate clinical
treatment in the future using delivery of suppressive Let-7.
PMID- 29336466
TI - Magnolol protects against ischemic-reperfusion brain damage following oxygen
glucose deprivation and transient focal cerebral ischemia.
AB - In the present study, the neuroprotective potential of magnolol against ischemia
reperfusion brain injury was examined via in vivo and in vitro experiments.
Magnolol exhibited strong radical scavenging and antioxidant activity, and
significantly inhibited the production of interleukin-6, tumor necrosis factor-a
and nitrite/nitrate (NOX) in lipopolysaccharide-stimulated BV2 and RAW 264.7
cells when applied at concentrations of 10 and 50 uM, respectively. Magnolol (100
uM) also significantly attenuated oxygen-glucose deprivation-induced damage in
neonatal rat hippocampal slice cultures, when administered up to 4 h following
the insult. In a rat model of stable ischemia, compared with a vehicle-treated
ischemic control, pretreatment with magnolol (0.01-1 mg/kg, intravenously)
significantly reduced brain infarction following ischemic stroke, and post
treatment with magnolol (1 mg/kg) remained effective and significantly reduced
infarction when administered 2 h following the onset of ischemia. Additionally,
magnolol (0.3 and 1 mg/kg) significantly reduced the accumulation of superoxide
anions at the border zones of infarction and reduced oxidative damage in the
ischemic brain. This was assessed by measuring the levels of NOX, malondialdehyde
and myeloperoxidase, the ratio of glutathione/oxidized glutathione and the
immunoreactions of 8-hydroxy-2'-deoxyguanosine and 4-hydroxynonenal. Thus,
magnolol was revealed to protect against ischemia-reperfusion brain damage. This
may be partly attributed to its antioxidant, radical scavenging and anti
inflammatory effects.
PMID- 29336467
TI - NOX4/ROS mediate ethanol-induced apoptosis via MAPK signal pathway in L-02 cells.
AB - The aim of the present study was to assess the molecular mechanism of ethanol
induced oxidative stress-mediated apoptosis in L-02 liver cells in order to
elucidate novel pathways associated with alcoholic liver disease. L-02 cells were
treated with 400 mM ethanol with or without inhibitors. The cell viability was
measured by an MTT assay. Cell apoptosis was assessed by flow cytometry and a
single-stranded DNA (ssDNA) assay. Intracellular reactive oxygen species (ROS)
production of L-02 cells was determined using the 2',7'-dichlorofluorescein
diacetate dye. The protein expression of c-Jun N-terminal kinase (JNK),
phosphorylated (p)-JNK, P38, p-P38, NADPH oxidase (NOX)1, NOX4, p22phox, B-cell
lymphoma 2 (Bcl-2) and Bcl-2-associated X protein were measured by western blot
analysis. The mRNA expression of NOX1, NOX4 and p22phox was measured by reverse
transcription polymerase chain reaction analysis. The results indicated that
after treatment with various concentrations of ethanol for the indicated
durations, L-02 cells were displayed a significant decrease in cell viability in
a dose-and time-dependent manner. Ethanol-induced apoptosis and cell death of L
02 cells was accompanied by the generation of ROS, elevated expression of NOX, as
well as phosphorylation of JNK and P-38. In addition, increased expression of Bcl
2 was induced by 400 mM ethanol. Furthermore, treatment with NOX inhibitor
attenuated the ethanol-induced a decrease in cell viability, and an increase in
apoptosis and Bcl-2 expression. In conclusion, ethanol induced apoptosis in the L
02 hepatocyte cell line via generation of ROS and elevated expression of NOX4.
This indicated that activation of JNK and p38 in the mitogen-activated protein
kinase pathway promotes apoptosis in L-02 cells.
PMID- 29336468
TI - Increased expression of sterol regulatory element binding protein-2 alleviates
autophagic dysfunction in NAFLD.
AB - Sterol regulatory element binding protein-2 (SREBP-2) is an important
transcription factor in lipid homeostasis. A previous study showed that SREBP-2
also activated autophagic genes during cell-sterol depletion. Alterations in
autophagy are reported to be involved in the pathogenesis of nonalcoholic fatty
liver disease (NAFLD). However, whether the regulation of SREBP-2 restores
dysfunctional autophagy in hepatocytes during NAFLD remains to be elucidated. In
the present study, a steatosis model was established with palmitic acid (PA)
treatment at the indicated times and concentrations. Autophagosomes in
hepatocytes were visualized by confocal microscopy after transfection with a
tandem GFP-mCherry-LC3 construct. Autophagy-associated protein levels were
analyzed by western blot analysis. Loss- and gain-of-function studies were
performed to examine the role of SREBP-2 in the regulation of hepatocyte
autophagy. It was demonstrated that PA induced autophagy and enhanced autophagic
flux at the early stage, whereas prolonged treatment with PA resulted in
dysfunction of autophagy in the PA-induced steatotic hepatocytes. In addition,
different cellular models presented with differing dysfunctional autophagy in
response to fatty acid overload. It was also confirmed that SREBP-2 regulated
autophagy-related gene expression in hepatocytes, and it was shown that the
overexpression of SREBP-2 increased the expression of autophagy-related genes,
but did not affect the inhibition of the autophagic flux in lipid-overloaded HL
7702 cells. By contrast, increased SREBP-2 partly restored the inhibited
autophagic activity in lipid-overloaded hepatoma HepG2 cells. Taken together, the
present study demonstrated that autophagic function was impaired in lipid
overloaded human hepatocytes, and the differential effect of PA on autophagy was
associated with the duration of PA and the cell type. Under these conditions, the
overexpression of SREBP-2 alleviated the inhibited autophagic activity rather
than the inhibition of autophagic flux. Consequently, the results indicated that
restoration of autophagy dysfunction via the regulation of SREBP-2 may be a
potential therapeutic target for the treatment of NAFLD.
PMID- 29336469
TI - Transcriptional regulation of HIV-1 host factor COMMD1 by the Sp family.
AB - Copper metabolism Murr1 domain containing 1 (COMMD1) has multiple functions in
the regulation of protein stability at the plasma membrane and in the cytoplasm.
However, the regulation of COMMD1 transcriptional has remained to be elucidated.
In the present study, the 5'-flanking region (-1,192/+83 bp) of the human COMMD1
gene was cloned. It was observed that the COMMD1 promoter region contains GC-rich
region that has 7 putative Sp1-binding sites via in silico analysis. The proximal
promoter region at -289/+83 bp was required for COMMD1 basal promoter activity by
deletion constructs of COMMD1 promoter. Moreover, Sp1 inhibitor, mithramycin A,
suppressed basal COMMD1 promoter activity. The Sp1-binding site (-11/-1 bp) in
the proximal promoter region was a critical site for COMMD1 gene regulation by
Sp1 and Sp3. Sp1 upregulated COMMD1 promoter activity, whereas Sp3 suppressed it.
Endogenous Sp1 and Sp3 bound to the proximal promoter region of COMMD1. Taken
together, Sp1 constitutively regulates the basal expression of the COMMD1 gene in
human epithelial cell lines.
PMID- 29336470
TI - TNF-alpha induces Drp1-mediated mitochondrial fragmentation during inflammatory
cardiomyocyte injury.
AB - Dynamin-related peptide 1 (Drpl)-mediated mitochondrial fission is an important
process associated with cardiac dysfunction under different pathological
conditions. The aim of the present study was to investigate the expression of
Drpl during inflammatory myocardial injury. Sprague-Dawley rats were treated
intraperitoneally with lipopolysaccharides (LPS). Furthermore, cultured H9C2
cardiomyocytes were treated with LPS, interleukin-6 (IL-6) and tumor necrosis
factor-alpha (TNF-alpha). Total and mitochondrial proteins were isolated from the
heart tissue of rats and from the H9C2 cardiomyocytes. Expression levels of Drp1
and RhoA were analyzed by western blotting. Mitochondrial morphology was
determined using confocal laser microscopy. The levels of mitochondrial Drp1 and
phosphorylated-Drp1 (p-Drp1) Ser616 were revealed to be increased in rats 6 h
after injection with LPS (5, 10 or 20 mg/kg). Furthermore, treatment with LPS and
IL-6 did not demonstrate a significant effect on the expression of total and
mitochondrial Drp1 in H9C2 cardiomyocytes in vitro; however, treatment with TNF
alpha (20 ng/ml) significantly enhanced the levels of mitochondrial Drp1 and p
Drp1 Ser616. Following TNF-alpha treatment, the expression of Ras homolog gene
family member A (RhoA) was also revealed to increase. Treatment with both Y-27632
and fasudil, [Rho kinase (ROCK) inhibitors], was demonstrated to attenuate the
otherwise TNF-alpha-induced increase in p-Drp1 Ser616 and mitochondrial Drp1. In
addition, it was revealed that Y-27632 and fasudil may also attenuate the TNF
alpha-induced increase in mitochondrial fragmentation and cell viability.
Therefore, the findings of the present study suggest that TNF-alpha is the
predominant inducer of Drp1 S616 phosphorylation during sepsis. The results of
the present study also suggest that the RhoA/ROCK pathway may be involved in the
phosphorylation and mitochondrial translocation of Drp1, which leads to
mitochondrial fragmentation.
PMID- 29336471
TI - Neuroprotective effects of p53/microRNA-22 regulate inflammation and apoptosis in
subarachnoid hemorrhage.
AB - The present study aimed to investigate whether the neuroprotective effects of
p53/microRNA-22 regulate inflammation and apoptosis in subarachnoid hemorrhage
(SAH). In a mouse model of SAH, microRNA-22 expression was upregulated. In
addition, downregulation of microRNA-22 in HEB cells increased the mRNA
expression levels of interleukin (IL)-6, induced cysteine rich angiogenic inducer
61 (Cyr61) expression, and suppressed the protein expression levels of B-cell
lymphoma 2-associated X protein (Bax) and caspase-3 activity. Treatment with the
p53 inhibitor, pifithrin-alpha, suppressed p53 protein expression, increased IL-6
mRNA expression, decreased microRNA-22 expression, Bax protein expression and
caspase-3 activity, and induced Cyr61 expression in mice with SAH. Furthermore,
p53 expression was knocked down using p53 small interfering RNA, which suppressed
microRNA-22 expression and increased IL-6 mRNA expression, inhibited Bax protein
expression and caspase-3 activity, and induced Cyr61 expression in HEB cells. The
present study demonstrated that the neuroprotective effects of p53/microRNA-22
may regulate inflammation and apoptosis in SAH. Reverse transcription
quantitative polymerase chain reaction (qPCR) was used to analyze the expression
of microRNA-22, western blot analysis was used to analyze the protein expression
of Bax and Cyr61.
PMID- 29336473
TI - Usefulness of identifying G-protein-coupled receptor dimers for diagnosis and
therapy of neurodegenerative diseases and of gliomas.
AB - Immunochemical detection of G-protein-coupled receptors (GPCRs) in cells and
tissues was a technical challenge for years. After the discovery of formation of
GPCR dimers/trimers/tetramers in transfected cells, a most recent challenge has
been to confirm receptor-receptor interactions in natural sources. The occurrence
of dimers or higher order oligomers is important from a therapeutic point of
view, mainly because their physiology/pharmacology is different from those of
individual receptors. On the one hand, pathophysiological factors need to count
more on GPCR dimers than on individual receptors. On the other hand, the
expression of dimers, trimers, etc. may change in pathological conditions and/or
along the course of a disease. This review will focus on G-protein-coupled
receptor dimers, on how to detect them by novel histological techniques and on
how the detection may be used in diagnosis and therapy of ailments of the central
nervous system, for instance in neurodegenerative diseases and gliomas.
PMID- 29336472
TI - Baicalin increases hair follicle development by increasing canonical Wnt/beta
catenin signaling and activating dermal papillar cells in mice.
AB - Baicalin is a traditional Chinese herbal medicine commonly used for hair loss,
the precise molecular mechanism of which is unknown. In the present study, the
mechanism of baicalin was investigated via the topical application of baicalin to
reconstituted hair follicles on mice dorsa and evaluating the effect on canonical
Wnt/beta-catenin signaling in the hair follicles and the activity of dermal
papillar cells. The results indicate that baicalin stimulates the expression of
Wnt3a, Wnt5a, frizzled 7 and disheveled 2 whilst inhibiting the Axin/casein
kinase 1alpha/adenomatous polyposis coli/glycogen synthase kinase 3beta
degradation complex, leading to accumulation of beta-catenin and activation of
Wnt/beta-catenin signaling. In addition, baicalin was observed to increase the
alkaline phosphatase levels in dermal papillar cells, a process which was
dependent on Wnt pathway activation. Given its non-toxicity and ease of topical
application, baicalin represents a promising treatment for alopecia and other
forms of hair loss. Further studies of baicalin using human hair follicle
transplants are warranted in preparation for future clinical use.
PMID- 29336474
TI - Exposure to violence, teacher support, and school delay amongst adolescents in
South Africa.
AB - BACKGROUND: Many adolescents in South Africa are exposed to multiple types of
violence, socio-economic disadvantage, and low-quality education: all risk
factors for educational outcomes including school delay (grade enrolment below
that which is age-appropriate). Supportive teacher-student relationships are
known to be associated with improved academic outcomes in high-income contexts.
AIMS: To investigate whether the academic and emotional support provided by
teachers can protect against school delay for adolescents exposed to multiple
types of violence and socio-economic disadvantage in South Africa. SAMPLE: High
risk sample of 503 adolescents aged 10-18 exposed to multiple types of violence
and socio-economic disadvantage at home, in school, and in their communities.
METHODS: Multilevel aggregated structural equation modelling was applied to
pre/post-RCT data. This investigated whether associations between adolescent
exposure to violence and school delay could be lessened by having teachers who
were academically and/or emotionally supportive. RESULTS: More frequent exposure
to 'poly-violence' and receiving more emotional support from teachers were
independently associated with greater school delay. On the contrary, higher
academic support from teachers was associated with lower school delay. Neither
academic nor emotional teacher support was found to moderate the relationship
between more frequent exposure to 'poly-violence' and an increased risk of
adolescent school delay. CONCLUSION: Adolescents' academic support from teachers
is low in poorly resourced school contexts in South Africa. School-based
secondary prevention programmes assisting teachers with more training and
academic support in deprived contexts have potential to reduce the impact of
violence and socio-economic disadvantage on adolescents' school delay.
PMID- 29336475
TI - Exosomes originating from MSCs stimulated with TGF-beta and IFN-gamma promote
Treg differentiation.
AB - Mesenchymal stem cells (MSCs) have been approved as a cellular drug for the
treatment of a variety of immune-related diseases by the government of many
countries'. Previous investigations, including ours, have shown that exosomes
secreted by MSCs (MSC-ex) are one of the main factors responsible for the
therapeutic effect of MSCs. However, the immune modulation activities and the
contents of MSC-ex derived from cells under different incubation conditions
differ dramatically. Therefore, the optimal way to ensure effectiveness is by
identifying and preparing MSC-ex with confirmed potent immunosuppressive
activity. The aim of this study was to investigate and analyze the composition
and function of MSC-ex secreted by MSCs stimulated by different cytokines to
obtain exosomes with more potent immunosuppressive activity. To achieve this aim,
umbilical cord-derived MSCs were treated with PBS, TGF-beta, IFN-gamma, or TGF
beta plus IFN-gamma for 72 hr. Then, exosomes were isolated from the culture
supernatants. Common exosome markers, such as CD9, CD63, and CD81, were detected
and analyzed by FCM. At the same time, the TGF-beta, IFN-gamma, IDO, and IL-10
content in exosomes was detected, and the influence of exosmes from defferent
groups on the induction of mononuclear cell transformation into Tregs was
analyzed via FCM. Our results show that the TGF-beta combined with IFN-gamma
exosome group more effectively promoted the transformation of mononuclear cells
to Tregs, and the analysis showed that IDO may play an important role. This study
might provide a novel strategy to treat GVHD as well as other immune-associated
disorders.
PMID- 29336476
TI - Drivers and demographic consequences of seasonal mass changes in an alpine
ungulate.
AB - We know little about the determinants and demographic consequences of the marked
seasonal mass changes exhibited by many northern and alpine mammals. We analysed
43 years of data on individual winter mass loss (the difference between mass in
early June and mass in mid-September the previous year) and summer mass gain (the
difference between mass in mid-September and in early June of the same year) in
adult bighorn sheep (Ovis canadensis). We calculated relative seasonal mass
change as a proportion of individual body mass at the start of each season. We
first examined the effects of weather and population density on relative changes
in body mass. We then assessed the consequences of relative seasonal mass changes
on reproduction. Mean April-May temperature was the main driver of relative
seasonal mass changes: warm springs reduced both relative winter mass loss and
summer mass gain of both sexes, likely partially due to a trade-off between
growth rate of plants and duration of access to high-quality forage. Because
these effects cancelled each other, spring temperature did not influence mass in
mid-September. Mothers that lost relatively more mass during the winter had lambs
that gained less mass during summer, likely because these females allocated fewer
resources to lactation. Winter survival of lambs increased with their summer mass
gain. In males, relative mass loss during winter, which includes the rut, did not
influence the probability of siring at least one lamb, possibly indicating that
greater mating effort did not necessarily translate into greater reproductive
success. Our findings improve our understanding of how weather influences
recruitment and underline the importance of cryptic mechanisms behind the effects
of climate change on demographic traits.
PMID- 29336477
TI - Intraoperative adverse events associated with extremely preterm cesarean
deliveries.
AB - INTRODUCTION: At the same time as survival is increasing among premature babies
born before 26 weeks of gestation, the rates of cesarean deliveries before 26
weeks is also rising. Our purpose was to compare the frequency of intraoperative
adverse events during cesarean deliveries in two gestational age groups: 24-25
weeks and 26-27 weeks. MATERIAL AND METHODS: This single-center retrospective
cohort study included all women with cesarean deliveries performed before 28+0
weeks from 2007 through 2015. It compared the frequency of intraoperative adverse
events between two groups: those at 24-25 weeks of gestation and at 26-27 weeks.
Intraoperative adverse events were a classical incision, transplacental incision,
difficulty in fetal extraction (explicitly mentioned in the surgical report),
postpartum hemorrhage (>=500 mL of blood loss), and injury to internal organs. A
composite outcome including at least one of these events enabled us to analyze
the risk factors for intraoperative adverse events with univariate and
multivariable analysis. Stratified analyses by the indication for the cesarean
were performed. RESULTS: We compared 74 cesarean deliveries at 24-25 weeks of
gestation and 214 at 26-27 weeks. Intraoperative adverse events occurred at
higher rates in the 24-25-week group (63.5 vs. 30.8%, p < 0.001). After
adjustment for confounding factors, this group remained at significantly higher
risk of intraoperative adverse events [adjusted odds ratio 5.04 (2.67-9.50)],
even after stratification by indication for the cesarean. CONCLUSION: These
results should help obstetricians and women making decisions about cesarean
deliveries at these extremely low gestational ages.
PMID- 29336478
TI - Apelin-13 treatment enhances the stability of atherosclerotic plaques.
AB - BACKGROUND: Apelin is an endogenous peptidergic system which modulates
cardiovascular function. Recent studies pointed out a fundamental contribution of
apelin on atherosclerosis development; however, such reports revealed
contradictory data, and to date, it is difficult to accurately define a
beneficial or deleterious role. To better understand apelin function on
atherosclerosis, we aimed to investigate apelin-13 treatment effects on
atherosclerotic plaques composition. DESIGN: Apolipoprotein E gene-deleted mice
were fed on Western-type diet for 11 weeks. Atherosclerotic plaque formation was
induced in the carotid artery by a shear stress modifier device, which exposes
the same vessel to distinct patterns of shear stress enabling the formation of
plaques with different composition. Mice were treated with apelin-13 (2 mg kg-1
day-1 ) or vehicle for the last 3 weeks. RESULTS: Apelin-13 treatment did not
alter the lipid content of low shear stress- and oscillatory shear stress-induced
plaques in the carotid. However, apelin-13 greatly ameliorated plaque stability
by increasing intraplaque collagen content and reducing MMP-9 expression.
Furthermore, apelin-13 decreased the infiltration of inflammatory cells
(neutrophil and macrophage) and intraplaque reactive oxygen species content.
Interestingly, apelin-13 treatment reduced total cholesterol, LDL levels and free
fatty acid serum levels, while HDL, triglycerides serum levels were not
significantly changed. CONCLUSIONS: Apelin-13 treatment for 3 weeks did not alter
the lesion size, but it significantly enhanced the stable phenotype of
atherosclerotic plaques and improved serum lipid profile. These results indicate
that activation of apelin system decreases plaque vulnerability.
PMID- 29336479
TI - Inhibition of glycolytic metabolism in glioblastoma cells by Pt3glc combinated
with PI3K inhibitor via SIRT3-mediated mitochondrial and PI3K/Akt-MAPK pathway.
AB - Glioblastoma multiforme (GBM) is the most malignant and aggressive glioma with
abnormal expression of genes that mediate glycolytic metabolism and tumor cell
growth. Petunidin-3-O- glucoside (Pt3glc) is a kind of anthocyanin in the red
grape and derived beverages, representing the most common naturally occurring
anthocyanins with a reduced incidence of cancer and heart diseases. In this
study, whether Pt3glc could effectively regulate glycolysis to inhibit GBM cell
was investigated by using the DBTRG-05MG cell lines. Notably, Pt3glc displayed
potent anti-proliferative activity and significantly changed the protein levels
related to both glycolytic metabolism and GBM cell survival. The expression of
the pro-apoptotic protein Bax was increased with concomitant reduction on the
levels of the anti-apoptotic protein Bcl-2 and caspase-3 activity. Furthermore,
the levels of survival signaling proteins, such as Akt and p-Akt (Scr473), ERK
and phospho-ERK, were significantly decreased by Pt3glc in combination with the
PI3K inhibitor of LY294002. Most importantly, the levels of SIRT3 and
phosphorylated p53 were also down-regulation, indicating that Pt3glc combinated
with PI3K inhibitor could induced GBM cell death may act via the SIRT3/p53
mediated mitochondrial and PI3K/Akt-ERK pathways. Our findings thus provide
rational evidence that the combination of Pt3glc with PI3K inhibitor, which
target alternative pathways in GBM cells, may be a useful adjuvant therapy in
glioblastoma treatment. This article is protected by copyright. All rights
reserved.
PMID- 29336480
TI - Species co-occurrence networks: Can they reveal trophic and non-trophic
interactions in ecological communities?
AB - Co-occurrence methods are increasingly utilized in ecology to infer networks of
species interactions where detailed knowledge based on empirical studies is
difficult to obtain. Their use is particularly common, but not restricted to,
microbial networks constructed from metagenomic analyses. In this study, we test
the efficacy of this procedure by comparing an inferred network constructed using
spatially intensive co-occurrence data from the rocky intertidal zone in central
Chile to a well-resolved, empirically based, species interaction network from the
same region. We evaluated the overlap in the information provided by each network
and the extent to which there is a bias for co-occurrence data to better detect
known trophic or non-trophic, positive or negative interactions. We found a poor
correspondence between the co-occurrence network and the known species
interactions with overall sensitivity (probability of true link detection) equal
to 0.469, and specificity (true non-interaction) equal to 0.527. The ability to
detect interactions varied with interaction type. Positive non-trophic
interactions such as commensalism and facilitation were detected at the highest
rates. These results demonstrate that co-occurrence networks do not represent
classical ecological networks in which interactions are defined by direct
observations or experimental manipulations. Co-occurrence networks provide
information about the joint spatial effects of environmental conditions,
recruitment, and, to some extent, biotic interactions, and among the latter, they
tend to better detect niche-expanding positive non-trophic interactions.
Detection of links (sensitivity or specificity) was not higher for well-known
intertidal keystone species than for the rest of consumers in the community.
Thus, as observed in previous empirical and theoretical studies, patterns of
interactions in co-occurrence networks must be interpreted with caution,
especially when extending interaction-based ecological theory to interpret
network variability and stability. Co-occurrence networks may be particularly
valuable for analysis of community dynamics that blends interactions and
environment, rather than pairwise interactions alone.
PMID- 29336481
TI - The "unguarded-X" and the genetic architecture of lifespan: Inbreeding results in
a potentially maladaptive sex-specific reduction of female lifespan in Drosophila
melanogaster.
AB - Sex differences in ageing and lifespan are ubiquitous in nature. The "unguarded
X" hypothesis (UXh) suggests they may be partly due to the expression of
recessive mutations in the hemizygous sex chromosomes of the heterogametic sex,
which could help explain sex-specific ageing in a broad array of taxa. A
prediction central to the UX hypothesis is that inbreeding will decrease the
lifespan of the homogametic sex more than the heterogametic sex, because only in
the former does inbreeding increase the expression of recessive deleterious
mutations. In this study, we test this prediction by examining the effects of
inbreeding on the lifespan and fitness of male and female Drosophila melanogaster
across different social environments. We found that, across social environments,
inbreeding resulted in a greater reduction of female than male lifespan, and that
inbreeding effects on fitness did not seem to counterbalance sex-specific effects
on lifespan, suggesting the former are maladaptative. Inter- and intra-sexual
correlation analyses also allowed us to identify evidence of an underlying joint
genetic architecture for inbreeding effects on lifespan. We discuss these results
in light of the UXh and other alternative explanations, and suggest that more
attention should be paid to the possibility that the "unguarded-X" may play an
important role in the evolution of sex-specific lifespan.
PMID- 29336482
TI - Litter removal in a tropical rain forest reduces fine root biomass and production
but litter addition has few effects.
AB - Many old-growth lowland tropical rain forests are potentially nutrient limited,
and it has long been thought that many such forests maintain growth by recycling
nutrients from decomposing litter. We investigated this by continuously removing
(for 10 yr) freshly fallen litter from five (45 m * 45 m) plots, adding it to
five other plots, there were five controls. From monthly measures over 1 yr we
show that litter removal caused lower: fine root (<=2 mm diameter) standing mass,
fine root standing length, fine root length production and fine root length
survivorship. Litter addition did not significantly change fine root mass or
length or production. Nutrient concentrations in fine roots in litter removal
plots were lower than those in controls for nitrogen (N), calcium (Ca) and
magnesium (Mg), concentrations in fine roots in litter addition plots were higher
for N and Ca. Chronic litter removal has resulted in reduced forest growth due to
lack of nutrients, probably nitrogen. Conversely, long-term litter addition has
had fewer effects.
PMID- 29336483
TI - Glucose metabolism during in vitro maturation of mouse oocytes: An study using
RNA interference.
AB - In previous studies on glucose metabolism during in vitro maturation, intact
cumulus-oocyte complexes (COCs) were treated with enzyme inhibitors/activators.
Because inhibitors/activators may have non-specificity and/or toxicity, and
culture of COCs cannot differentiate whether glucose metabolism of cumulus cells
(CCs) or that of the oocyte supports oocyte maturation, results from the previous
studies must be verified by silencing genes in either CCs or cumulus-denuded
oocytes (DOs). In this study, RNAi was adopted to specify the effects of glucose
metabolism in CCs or DOs on oocyte maturation. Although silencing either
glyceraldehyde 3-phosphate dehydrogenase (GAPDH) or glucose-6-phosphate
dehydrogenase (G6PD) genes in CCs significantly decreased competence of the
cocultured DOs, silencing G6PD impaired competence to a greater extent. While
silencing G6PD or GAPDH of CCs decreased glutathione and ATP contents of
cocultured DOs to similar extents, silencing G6PD increased oxidative stress as
well. Analysis on metabolite contents and oxidative stress index and culture of
DOs in medium conditioned with gene-silenced CCs indicated that CCs supported
oocyte maturation by releasing glucose metabolites. Silencing mitochondrial
pyruvate carrier 1 or NADH dehydrogenase (ubiquintone) flavoprotein 1 of DOs
significantly impaired their maturation. The results have unequivocally confirmed
that CCs promote oocyte maturation by releasing glucose metabolites from both
pentose phosphate pathway (PPP) and glycolysis. Pyruvate is transferred into DOs
by mitochondrial pyruvate carrier (MPC) and utilized through mitochondrial
electron transport to support maturation.
PMID- 29336484
TI - Epigenetic regulation of megakaryocytic and erythroid differentiation by PHF2
histone demethylase.
AB - Plant homeodomain finger 2 (PHF2) is a JmjC family histone demethylase that
demethylates H3K9me2, a repressive gene marker. PHF2 was found to play a role in
the differentiation of several tissue types such as osteoblast and adipocyte
differentiation. We report here that PHF2 plays a role in the epigenetic
regulation of megakaryocytic (MK) and erythroid differentiation. We investigated
PHF2 expression during MK and erythroid differentiation in K562 and human CD34+
progenitor (hCD34+ ) cells. Our data demonstrate that PHF2 expression is down
regulated during megakaryopoiesis and erythropoiesis. PHF2 has a negative role in
MK and erythroid differentiation of K562 cells; knockdown of PHF2 promotes MK and
erythroid differentiation of hCD34+ cells. Similarly, we found that p53
expression is also down-regulated during MK and erythroid differentiation, which
parallels PHF2 expression. PHF2 binds to the p53 promoter and regulates the
expression of p53 by demethylating H3K9me2 in the promoter region of p53. Taken
together, our data show that PHF2 is a negative epigenetic regulator of MK and
erythroid differentiation, and that one of the pathways through which PHF2
affects MK and erythroid differentiation is via regulation of p53 expression.
PMID- 29336485
TI - A multimodal microcharacterisation of trace-element zonation and crystallographic
orientation in natural cassiterite by combining cathodoluminescence, EBSD, EPMA
and contribution of confocal Raman-in-SEM imaging.
AB - In cassiterite, tin is associated with metals (titanium, niobium, tantalum,
indium, tungsten, iron, manganese, mercury). Knowledge of mineral chemistry and
trace-element distribution is essential for: the understanding of ore formation,
the exploration phase, the feasibility of ore treatment, and disposal/treatment
of tailings after the exploitation phase. However, the availability of analytical
methods make these characterisations difficult. We present a multitechnical
approach to chemical and structural data that includes scanning electron
microscopy (SEM)-based imaging and microanalysis techniques such as: secondary
and backscattered electrons, cathodoluminescence (CL), electron probe
microanalyser (EPMA), electron backscattered diffraction (EBSD) and confocal
Raman-imaging integrated in a SEM (RISE). The presented results show the
complementarity of the used analytical techniques. SEM, CL, EBSD, EPMA provide
information from the interaction of an electron beam with minerals, leading to
atomistic information about their composition, whereas RISE, Raman spectroscopy
and imaging completes the studies with information about molecular vibrations,
which are sensitive to structural modifications of the minerals. The correlation
of Raman bands with the presence/absence of Nb, Ta, Fe (heterovalent
substitution) and Ti (homovalent substitution) is established at a submicrometric
scale. Combination of the different techniques makes it possible to establish a
direct link between chemical and crystallographic data of cassiterite.
PMID- 29336486
TI - Preventing post-traumatic stress disorder following childbirth and traumatic
birth experiences: a systematic review.
AB - INTRODUCTION: Between 9 and 44% of women experience giving birth as traumatic,
and 3% of women develop a post-traumatic stress disorder following childbirth.
Knowledge on risk factors is abundant, but studies on treatment are limited. This
study aimed to present an overview of means to prevent traumatic birth
experiences and childbirth-related post-traumatic stress disorder. MATERIAL AND
METHODS: Major databases [Cochrane; Embase; PsycINFO; PubMed (Medline)] were
searched using combinations of the key words and their synonyms. RESULTS: After
screening titles and abstracts and reading 135 full-text articles, 13 studies
were included. All evaluated secondary prevention, and none primary prevention.
Interventions included debriefing, structured psychological interventions,
expressive writing interventions, encouraging skin-to-skin contact with healthy
newborns immediately postpartum and holding or seeing the newborn after
stillbirth. The large heterogeneity of study characteristics precluded pooling of
data. The writing interventions to express feelings appeared to be effective in
prevention. A psychological intervention including elements of exposure and
psycho-education seemed to lead to fewer post-traumatic stress disorder symptoms
in women who delivered via emergency cesarean section. CONCLUSIONS: No research
has been done on primary prevention of traumatic childbirth. Research on
secondary prevention of traumatic childbirth and post-traumatic stress disorder
following delivery provides insufficient evidence that the described
interventions are effective in unselected groups of women. In certain subgroups,
results are inhomogeneous.
PMID- 29336487
TI - Mig6 reduces inflammatory mediators production by regulating the activation of
EGFR in LPS-induced endotoxemia.
AB - Epithelial growth factor receptor (EGFR), a tyrosine kinase receptor, plays a
critical role in lipopolysaccharide (LPS)-induced endotoxemia. Meanwhile, EGFR
signaling is regulated by multiple feedback regulators, including mitogen
inducible gene 6 protein (Mig6). However, as an EGFR regulator, the role of Mig6
in endotoxemia is still remained unknown. Here, we reported for the first time
that LPS treatment increased the expression of Mig6 and this effect could be
inhibited by EGFR inhibitor, PD168393 or erlotinib. Furthermore, knocking down of
Mig6 expression led to increased EGFR activation and inflammatory mediators (TNF
alpha, il-1beta) production in response to LPS treatment. On the other hand, the
increased EGFR activation and TNF-alpha or il-1beta production in LPS treatment
could be inhibited by Mig6 overexpression. Besides, in LPS-induced endotoxemia,
ERK1/2 and p-38 activation required Mig6. All these results indicated that Mig6
regulates the production of inflammatory mediators (TNF-alpha, il-1beta) through
inhibiting the over activation of EGFR, which in turn inhibit MAPKs signaling
(ERK1/2, p-38). These finding suggested that Mig6 may be a novel potential target
for controlling the over inflammatory response in endotoxemia.
PMID- 29336489
TI - Executive summary of the methods report for 'The EAACI/GA2 LEN/EDF/WAO Guideline
for the Definition, Classification, Diagnosis and Management of Urticaria. The
2017 Revision and Update'.
PMID- 29336488
TI - Neonatal Ethanol Exposure Causes Behavioral Deficits in Young Mice.
AB - BACKGROUND: Fetal ethanol (EtOH) exposure can damage the developing central
nervous system and lead to cognitive and behavioral deficits, known as fetal
alcohol spectrum disorders (FASD). EtOH exposure to mouse pups during early
neonatal development was used as a model of EtOH exposure that overlaps the human
third-trimester "brain growth spurt"-a model that has been widely used to study
FASD in rats. METHODS: C57BL/6 male and female mice were exposed to EtOH (4
g/kg/d) on postnatal days (PD) 4 to 10 by oral intubation. Intubated and
nontreated controls were also included. Behavioral testing of the offspring,
including open field, elevated plus maze, and Morris water maze, was performed on
PD 20 to 45. RESULTS: EtOH exposure during PD 4 to 10 resulted in hyperactivity
and deficits in learning and memory in young mice with no apparent sex
differences. CONCLUSIONS: Based on these data, this neonatal intubation mouse
model may be useful for future mechanistic and genetic studies of FASD and for
screening of novel therapeutic agents.
PMID- 29336490
TI - Progress towards a methodology for high throughput 3D reconstruction of soot
nanoparticles via electron tomography.
AB - The aim of this work is to make progress towards the development of 3D
reconstruction as a legitimate alternative to traditional 2D characterization of
soot. Time constraints are the greatest opposition to its implementation, as
currently reconstruction of a single soot particle takes around 5-6 h to
complete. As such, the accuracy and detail gains are currently insufficient to
challenge 2D characterization of a representative sample (e.g. 200 particles).
This work is a consideration of the optimization of the steps included within the
computational reconstruction and manual segmentation of soot particles. Our
optimal process reduced the time required by over 70% in comparison to a typical
procedure, whilst producing models with no appreciable decrease in quality.
PMID- 29336491
TI - Effect of sex steroid hormone fluctuations in the pathophysiology of male-retinal
pigment epithelial cells.
AB - Gender-based differences may influence the occurrence of several ocular
conditions suggesting the possibility that fluctuations in sex steroid
homeostasis may have direct effects on the eye physiology. Here, we evaluated the
effect of sex steroid hormone fluctuations in male retinal pigment epithelial
cells, RPEs (ARPE-19). To mimic hormonal fluctuations occurring during aging, we
exposed ARPE-19 to acute, prolonged or chronic estradiol, and progesterone
challenges. We found that chronic estradiol treatment promotes a remarkable
necrosis of RPE cells, and does not affect pRb2/p130 or PAI-2 sub-cellular
localization. In contrast, chronic progesterone exposure induces nuclear
subcellular rearrangement of pRb2/p130, co-immunolocalization of pRb2/p130 with
PAI-2, and accumulation of cells in G2/M phase, which is accompanied by a
remarkable reduction of necrosis in favour of apoptosis activation. This study
has a high clinical significance since it considers sex steroid fluctuations as
inducers of milieu change in the retina able to influence pathological situations
occurring with aging in non-reproductive systems such as the eye. Exogenous
administration of physiologically significant amounts of sex hormones for long
periods of time is a common clinical practice for transgender patients seeking
sex reassignment. In particular, our study offers the unique opportunity to
unravel the effects of sex hormones, not only in determining gender differences
but also in affecting the physiology of non-reproductive systems, such as the
eye, in the underserved transgender community.
PMID- 29336492
TI - Joint effects of chlorpyrifos and mancozeb on the terrestrial isopod
Porcellionides pruinosus: A multiple biomarker approach.
AB - The exposure to pesticides by nontarget soil biota has long been regarded as a
serious downside of modern agricultural regimes and the subject of heated debate.
Of utmost relevance is the exposure to pesticide mixtures because their effects
have been shown to not necessarily reflect the individual toxicity of their
components, and even the simple addition of effects may lead to consequences not
clearly anticipated. In the present study, a multiple biomarker approach was
employed to identify the mechanistic and time effects underlying several single
and mixture treatments of chlorpyrifos (CPF) and mancozeb (MCZ) in juveniles and
adults of the terrestrial isopod Porcellionides pruinosus. The effects of the
individual pesticides and the mixtures at recommended doses were mostly
transitory under these controlled conditions and one-pulse exposure. Whereas
imbalances were identified on detoxification and oxidative stress-related
enzymes, the isopods generally showed the ability to recover through the end of
the experiment. However, juveniles displayed greater vulnerability than adults.
Most of the differences between life stages occurred in energy-related parameters
where distinct performances and stress-handling behaviors were observed,
suggesting higher metabolic costs to juveniles. Our results stress that
understanding the time dependence of the underlying mechanisms governing the
joint effects of the pesticides can help in assessing and anticipating the
effects of the pesticide mixtures. Moreover, we emphasize the importance of
taking life stage-related differences into consideration when evaluating the
environmental risks of pesticides and pesticide mixtures. Environ Toxicol Chem
2018;37:1446-1457. (c) 2018 SETAC.
PMID- 29336494
TI - Conditional neuromodulation of neurogenic detrusor overactivity using transrectal
stimulation in patients with spinal cord injury: A proof of principle study.
Knight SL, Edirisinghe N, Leaker B, Susser J, Craggs MD, Neurourol Urodyn. 2017
Jun 30.
PMID- 29336493
TI - N-Terminal Cu-Binding Motifs (Xxx-Zzz-His, Xxx-His) and Their Derivatives:
Chemistry, Biology and Medicinal Applications.
AB - Peptides and proteins with N-terminal amino acid sequences NH2 -Xxx-His (XH) and
NH2 -Xxx-Zzz-His (XZH) form well-established high-affinity CuII -complexes. Key
examples are Asp-Ala-His (in serum albumin) and Gly-His-Lys, the wound healing
factor. This opens a straightforward way to add a high-affinity CuII -binding
site to almost any peptide or protein, by chemical or recombinant approaches.
Thus, these motifs, NH2 -Xxx-Zzz-His in particular, have been used to equip
peptides and proteins with a multitude of functions based on the redox activity
of Cu, including nuclease, protease, glycosidase, or oxygen activation
properties, useful in anticancer or antimicrobial drugs. More recent research
suggests novel biological functions, mainly based on the redox inertness of CuII
in XZH, like PET imaging (with 64 Cu), chelation therapies (for instance in
Alzheimer's disease and other types of neurodegeneration), antioxidant units, Cu
transporters and activation of biological functions by strong CuII binding. This
Review gives an overview of the chemical properties of Cu-XH and -XZH motifs and
discusses the pros and cons of the vastly different biological applications, and
how they could be improved depending on the application.
PMID- 29336495
TI - Acute toxicity of 6 neonicotinoid insecticides to freshwater invertebrates.
AB - Neonicotinoids are a group of insecticides commonly used in agriculture. Due to
their high water solubility, neonicotinoids can be transported to surface waters
and have the potential to be toxic to aquatic life. The present study assessed
and compared the acute (48- or 96-h) toxicity of 6 neonicotinoids (acetamiprid,
clothianidin, dinotefuran, imidacloprid, thiacloprid, and thiamethoxam) to 21
laboratory-cultured and field-collected aquatic invertebrates spanning 10 aquatic
arthropod orders. Test conditions mimicked species' habitat, with lentic taxa
exposed under static conditions, and lotic taxa exposed under recirculating
systems. Median lethal concentrations (LC50s) and median effect concentrations
(EC50s; immobility) were calculated and used to construct separate lethal- and
immobilization-derived species sensitivity distributions for each neonicotinoid,
from which 5th percentile hazard concentrations (HC5s) were calculated. The
results showed that the most sensitive invertebrates were insects from the orders
Ephemeroptera (Neocloeon triangulifer) and Diptera (Chironomus dilutus), whereas
cladocerans (Daphnia magna, Ceriodaphnia dubia) were the least sensitive. The
HC5s were compared with neonicotinoid environmental concentrations from Ontario
(Canada) monitoring studies. For all neonicotinoids except imidacloprid, the
resulting hazard quotients indicated little to no hazard in terms of acute
toxicity to aquatic communities in Ontario freshwater streams. For the
neonicotinoid imidacloprid, a moderate hazard was found when only invertebrate
immobilization, and not lethality, data were considered. Environ Toxicol Chem
2018;37:1430-1445. (c) 2018 SETAC.
PMID- 29336496
TI - Donepezil Reverses Dendritic Spine Morphology Adaptations and Fmr1 Epigenetic
Modifications in Hippocampus of Adult Rats After Adolescent Alcohol Exposure.
AB - BACKGROUND: Adolescent intermittent ethanol (AIE) exposure produces persistent
impairments in cholinergic and epigenetic signaling and alters markers of
synapses in the hippocampal formation, effects that are thought to drive
hippocampal dysfunction in adult rodents. Donepezil (Aricept), a cholinesterase
inhibitor, is used clinically to ameliorate memory-related cognitive deficits.
Given that donepezil also prevents morphological impairment in preclinical models
of neuropsychiatric disorders, we investigated the ability of donepezil to
reverse morphological and epigenetic adaptations in the hippocampus of adult rats
exposed to AIE. Because of the known relationship between dendritic spine density
and morphology with the fragile X mental retardation 1 (Fmr1) gene, we also
assessed Fmr1 expression and its epigenetic regulation in hippocampus after AIE
and donepezil pretreatment. METHODS: Adolescent rats were administered
intermittent ethanol for 16 days starting on postnatal day 30. Rats were treated
with donepezil (2.5 mg/kg) once a day for 4 days starting 20 days after the
completion of AIE exposure. Brains were dissected out after the fourth donepezil
dose, and spine analysis was completed in dentate gyrus granule neurons. A
separate cohort of rats, treated identically, was used for molecular studies.
RESULTS: AIE exposure significantly reduced dendritic spine density and altered
morphological characteristics of subclasses of dendritic spines. AIE exposure
also increased mRNA levels and H3-K27 acetylation occupancy of the Fmr1 gene in
hippocampus. Treatment of AIE-exposed adult rats with donepezil reversed both the
dendritic spine adaptations and epigenetic modifications and expression of Fmr1.
CONCLUSIONS: These findings indicate that AIE produces long-lasting decreases in
dendritic spine density and changes in Fmr1 gene expression in the hippocampal
formation, suggesting morphological and epigenetic mechanisms underlying
previously reported behavioral deficits after AIE. The reversal of these effects
by subchronic, post-AIE donepezil treatment indicates that these AIE effects can
be reversed by up-regulating cholinergic function.
PMID- 29336497
TI - Effects of treatment with Maraviroc a CCR5 inhibitor on a human hepatic stellate
cell line.
AB - After an acute liver damage, tissue regeneration repairs lesions with degradation
of deposed fibrotic material, while mechanisms of tissue restoration are
persistently activated following several repeated injuries, inducing deposition
of extracellular matrix. (ECM). Factors responsible for ECM remodeling have been
identified in a pathway involving a family of zinc-dependent enzyme matrix
metalloproteinases (MMPs), together with tissue inhibitor of metalloproteinases
(TIMPs). Recent experimental models suggested a role of CCR5 receptor in the
genesis of liver fibrosis. Drawing from these background we decided to evaluate
the effects of the treatment with the CCR5 inhibitor Maraviroc on LX-2, a human
hepatic stellate cell line (HSC). Treatment with Maraviroc resulted in a block in
S phase of LX-2 cells with increased expression levels of cyclin D1 and p21 while
the expression of p53 was reduced. Treatment with Maraviroc was also able to
block the accumulation of fibrillar collagens and extracellular matrix proteins
(ECM), as demonstrated by the decrease of specific markers as Collagen type I,
alpha-SMA, and TGF-beta1. In addition we observed a down regulation of both
metalloproteins (MMP-2, MMP-9), used for the degradation of the extracellular
matrix and their inhibitors (TIMP-1, TIMP-2). The identification of a compound
that may modulate the dynamic of liver fibrosis could be crucial in all chronic
liver diseases. Maraviroc could play an important role because, in addition to
its own anti-HIV activity, it could reduce the release of pro-inflammatory
citokynes implicated in liver fibrogenesis.
PMID- 29336498
TI - Erratum for Ann. N.Y. Acad. Sci. 2009. 1173: 670-674.
PMID- 29336499
TI - Ecologically Driven Ultrastructural and Hydrodynamic Designs in Stomatopod
Cuticles.
AB - Ecological pressures and varied feeding behaviors in a multitude of organisms
have necessitated the drive for adaptation. One such change is seen in the
feeding appendages of stomatopods, a group of highly predatory marine
crustaceans. Stomatopods include "spearers," who ambush and snare soft bodied
prey, and "smashers," who bludgeon hard-shelled prey with a heavily mineralized
club. The regional substructural complexity of the stomatopod dactyl club from
the smashing predator Odontodactylus scyllarus represents a model system in the
study of impact tolerant biominerals. The club consists of a highly mineralized
impact region, a characteristic Bouligand architecture (common to arthropods),
and a unique section of the club, the striated region, composed of highly aligned
sheets of mineralized fibers. Detailed ultrastructural investigations of the
striated region within O. scyllarus and a related species of spearing stomatopod,
Lysiosquillina maculate show consistent organization of mineral and organic, but
distinct differences in macro-scale architecture. Evidence is provided for the
function and substructural exaptation of the striated region, which facilitated
redeployment of a raptorial feeding appendage as a biological hammer. Moreover,
given the need to accelerate underwater and "grab" or "smash" their prey, the
spearer and smasher appendages are specifically designed with a significantly
reduced drag force.
PMID- 29336500
TI - 9,9'-Bifluorenylidene-Core Perylene Diimide Acceptors for As-Cast Non-Fullerene
Organic Solar Cells: The Isomeric Effect on Optoelectronic Properties.
AB - Two different non-fullerene small-molecule acceptors, m-PIB and p-PIB, based on
9,9'-bifluorenylidene (BF) and perylene diimide (PDI) were designed and
synthesized. Four beta-substituted PDIs were linked to BF in different positions.
Based on DFT analysis, derivative p-PIB exhibited reduced intramolecular twisting
between the PDI moieties, more delocalized wave function, and sufficiently wider
pi-electron delocalization than that of m-PIB. The absorption ability of p-PIB
was enhanced due to increased intermolecular interactions. By blending p-PIB with
poly{4,8-bis[5-(2ethylhexyl)thiophen-2-yl]benzo[1,2-b:4,5-b']dithiophene-co-3
fluorothieno[3,4-b]-thiophene-2-carboxylate} (PTB7-Th), organic solar cells
(OSCs) based on p-PIB obtained a maximum power conversion efficiency of 5.95 %
without any treatments. Due to the improved and balanced hole and electron
mobilities, the short-circuit current and fill factor of OSCs based on PTB7-Th
and p-PIB were significantly increased. The AFM and TEM results revealed that the
PTB7-Th:p-PIB film had favorable nanoscale phase separation and formed a
bicontinuous interpenetrating network.
PMID- 29336501
TI - Uncontrolled asthmatics have increased FceRI+ and TGF-beta-positive MCTC mast
cells and collagen VI in the alveolar parenchyma.
AB - BACKGROUND: Asthma has been associated with increased collagen deposition in both
conducting airways and alveolar parenchyma. Mast cells (MCs) are key effector
cells in asthma and have the ability to affect collagen synthesis. However, the
link between clinical control and changes in bronchial and alveolar MC phenotypes
and specific collagens in controlled and uncontrolled asthma remains unknown.
OBJECTIVE: To investigate MC phenotypes in correlation with deposition of
specific collagen subtypes in patients with controlled and uncontrolled asthma as
well as to healthy controls. METHODS: The tissue expression of IgE+ ,
FcepsilonRI+ and TGF-beta+ MCs, as well as immunoreactivity of collagen I, III
and VI, was assessed using immunohistochemistry on bronchial and transbronchial
biopsies from controlled asthmatics (n = 9), uncontrolled asthmatics (n = 16) and
healthy controls (n = 8). RESULTS: In the alveolar parenchyma, the total number
of MCs, as well as the number of FcepsilonRI+ MCs and pro-fibrotic TGF-beta+
MCTC, was significantly increased in uncontrolled asthma compared to both
controlled asthma and healthy controls. The proportion of TGF-beta+ MCTC
correlated positively to an increased immunoreactivity of alveolar collagen VI
but not collagen I and III. Collagen VI was increased in the alveolar parenchyma
of uncontrolled asthmatics compared to controlled asthmatics. Controlled
asthmatics had an increased deposition of alveolar collagen I. In bronchi, the
immunoreactivity of collagen I was increased in both controlled and uncontrolled
asthmatics while collagen III was increased only in controlled asthmatics.
CONCLUSIONS: Patients with uncontrolled atopic asthma have an altered pro
fibrotic MCTC phenotype in the alveolar parenchyma that is associated with
alveolar collagen VI. The present data thus support distal lung mast cell and
matrix changes as histopathological features of asthma that may be of particular
clinical relevance in patients who have remaining symptoms despite conventional
inhaler therapy.
PMID- 29336502
TI - Nursing teamwork in a health system: A multisite study.
AB - AIM: The aim of this study was to examine how the facets of teamwork exist among
nurse-only teams in acute and continuing care settings. BACKGROUND: The health
care 'team' conventionally describes the interdisciplinary team in both
literature and practice. Nursing-specific teams are rarely considered in the
literature. An examination of this specific professional cohort is important to
understand how teamwork exists among those who provide the majority of patient
care. METHOD: This was a descriptive, comparative, cross-sectional study using
the Nursing Teamwork Survey to measure teamwork of nursing-based teams among 1414
participants in multiple acute care environments across a large Midwestern health
system. RESULTS: The characteristics of nursing teams were analysed. The results
from the subscales within the teamwork model showed that nursing teams had a good
understanding of the various roles and responsibilities. However, nurse team
members held a more individualistic rather than collective team-oriented mindset.
CONCLUSIONS AND IMPLICATIONS FOR NURSING MANAGEMENT: Increased teamwork has a
positive effect on job satisfaction, staffing efficiencies, retention and care
delivery. Nurse leaders can use the information provided in this study to target
the aspects of highly functioning teams by improving team orientation, trust and
backup behaviours.
PMID- 29336503
TI - Sappinia sp. (Amoebozoa: Thecamoebida) and Rosculus sp. (SAR: Cercozoa) Isolated
From King Penguin Guano Collected in the Subantarctic (South Georgia, Salisbury
Plain) and their Coexistence in Culture.
AB - Two amoeboid organisms of the genera Sappinia Dangeard, 1896 and Rosculus Hawes,
1963 were identified in a sample containing king penguin guano. This sample,
collected in the Subantarctic, enlarges the list of fecal habitats known for the
presence of coprophilic amoebae. The two organisms were co-isolated and
subcultured for over 6 mo, with continuous efforts being invested to separate
each one from the mixed culture. In the mixed culture, Rosculus cells were fast
growing, tolerated changes in culturing conditions, formed cysts, and evidently
were attracted by Sappinia trophozoites. The separation of the Rosculus strain
was accomplished, whereas the Sappinia strain remained intermixed with
inseparable Rosculus cells. Sappinia cell populations were sensitive to changes
in culturing conditions; they improved with reduction of Rosculus cells in the
mixed culture. Thick-walled cysts, reportedly formed by Sappinia species, were
not seen. The ultrastructure of both organisms was congruent with the currently
accepted generic characteristics; however, some details were remarkable at the
species level. Combined with the results of phylogenetic analyses, our findings
indicate that the ultrastructure of the glycocalyx and the presence/absence of
the Golgi apparatus in differential diagnoses of Sappinia species require a
critical re-evaluation.
PMID- 29336504
TI - Wolbachia-induced transcription factor GATA4 suppresses ovary-specific genes
blastoderm-specific protein 25D and imaginal disc growth factor.
AB - The endosymbiotic bacterium Wolbachia infects a wide array of insect hosts and
has been implicated in a range of biological modifications as a consequence of
its infection. Previously, it was shown that the transcription factor GATA4 was
significantly induced in Wolbachia wMelPop-CLA strain infected Aedes aegypti
whole mosquitoes and cells. Here, we provide evidence that this induction also
occurs in mosquito ovaries where the ovary-specific genes blastoderm-specific
protein 25D (Bsg25D) and imaginal disc growth factor (Disc) are suppressed by
Wolbachia. We further demonstrate that transcriptional depletion of GATA4 results
in upregulation of both genes and conversely its overexpression leads to
downregulation of the genes, suggesting that Wolbachia-induced GATA4 plays a
suppressive regulatory role with regards to Bsg25D and Disc expression in
mosquito ovaries. When the Disc gene was silenced in mosquitoes, we did not
observe any difference in the number of mature ovarian follicles developed
between treatment groups. However, we did find a significant delay in the
hatching of eggs that had been laid by Disc knockdown mosquitoes.
PMID- 29336505
TI - Signalling transduction events involved in agonist-induced PGE2/EP4 receptor
externalization in cultured rat dorsal root ganglion neurons.
AB - BACKGROUND: Prostaglandin E2 (PGE2) enriched in inflamed tissues contributes to
chronic pain by sensitizing nociceptive dorsal root ganglion (DRG) neurons
(nociceptors). Of four PGE2 receptors (EP1-4), EP4 plays a major role in PGE2
induced nociceptor sensitization. We have previously reported that PGE2 or EP4
agonists stimulated EP4 externalization in cultured DRG neurons and this event
contributes to nociceptor sensitization. However, the signalling transduction
events governing this event remain unknown. METHODS: In this study, using
antibody-based externalization assay, we examined EP subtypes and multiple
signalling transduction events involved in PGE2-induced EP4 externalization in
cultured DRG neurons. RESULTS: In addition to EP4 agonist, EP2 agonist, to a
lesser extent, also induced EP4 externalization while EP1 and EP3 agonists had no
effect. The extracellular and intracellular calcium chelators, the inhibitors of
CaMKII, cAMP, PKA, PKC, PKCepsilon, PLC, MAPKs, PI3K and Akt suppressed agonist
induced EP4 externalization. The activator of AC, two PKA-specific cAMP analogues
and one Epac-specific cAMP analogue also induced EP4 externalization. ELISA
showed that double sequential exposures to EP4 agonists induced a greater release
of pain peptide CGRP from cultured DRG neurons than a single exposure, an event
blocked by the inhibitor of anterograde transport from ER/Golgi complex to cell
surface. CONCLUSIONS: Taken together, these data suggest that mobilization of
extracellular and intracellular calcium as well as the activation of CaMKII,
cAMP/PKA, cAMP/Epac, PKC/PKCepsilon, MAPKs, PI3K-Akt and PLC signalling
transduction pathways are involved in agonist-induced EP4 externalization.
Agonist-enhanced EP4 externalization increases EP4 cell surface abundance and
activity, thus enhancing nociceptor sensitization. SIGNIFICANCE: This study adds
mechanistic information regarding signalling transduction events involved in
agonist-induced EP4 cell surface trafficking. EP4 and EP2 (to lesser extent)
receptors, extra- and intracellular Ca++ , CaKMII, cAMP, PKA, PKC, PKCepsilon,
PLC, MAPK, PI3K and Akt are involved in this event. Agonist-induced EP4
externalization contributes to enhanced nociceptor sensitization.
PMID- 29336506
TI - Influence of culture change on the perception of fear and anxiety pathways in
Endodontics: A pilot proof of concept study.
AB - This study assessed the influence of cultural changes (known as acculturation) on
pathways of fear and anxiety in Endodontics. A purposive sampling technique
identified patients of Saudi Arabian descent living in Australia and Saudi
Arabia. Only patients with root canal fillings (or treatment planned for
endodontic treatment) were included. Patients with intellectual disabilities,
surgical root therapy, and aged under 20 were excluded. Consenting patients
attending the dental clinics of University of Griffith University, Australia and
University of Dammam, Saudi Arabia completed the "My Endodontic Fear
Questionnaire." Three hundred and twenty-four patients (21-75 years) were
included, 90% of participants reported more than one pathway. Australian Saudi
Arabians mainly utilised vicarious pathway (94.9%), whilst Saudi Arabians
utilised the verbal threat (93.5%) and parental pathway (78.3%). This study
highlights the possible role of acculturation on the perception of fear and
anxiety in Endodontics; however, further research with other ethnic groups is
essential to enhance our understanding.
PMID- 29336507
TI - "LEARN"ing what is important to children and young people with intellectual
disabilities when they are in hospital.
AB - BACKGROUND: The need to review health service provision for children and young
people (CYP) with disabilities and their families in the United Kingdom has been
expressed in multiple reports: the most consistent message being that services
need to be tailored to meet their individual needs. Our aim was to understand the
hospital-related needs and experiences of CYP with intellectual disabilities.
METHOD: An ethnographic study of a neurosciences ward and outpatient department
was conducted within a paediatric tertiary hospital setting. RESULTS: Five
themes, developed using the acronym LEARN, explained what is important to CYP
with intellectual disabilities in hospital: (i) little things make the biggest
difference, (ii) eliminate unnecessary waiting, (iii) avoid boredom, (iv) routine
and home comforts are key and (v) never assume. CONCLUSIONS: It is imperative
that the present authors continue to challenge the idea that it is acceptable to
exclude CYP with intellectual disabilities from research because of their
inability to participate.
PMID- 29336508
TI - National audit of perinatal HIV infections in the UK, 2006-2013: what lessons can
be learnt?
AB - OBJECTIVES: The aim of the study was to investigate circumstances surrounding
perinatal transmissions of HIV (PHIVs) in the UK. METHODS: The National Study of
HIV in Pregnancy and Childhood conducts comprehensive surveillance of all
pregnancies in women diagnosed with HIV infection and their infants in the UK;
reports of all HIV-diagnosed children are also sought, regardless of country of
birth. Children with PHIV born in 2006-2013 and reported by 2014 were included in
an audit, with additional data collection via telephone interviews with
clinicians involved in each case. Contributing factors for each transmission were
identified, and cases described according to main likely contributing factor, by
maternal diagnosis timing. RESULTS: A total of 108 PHIVs were identified. Of the
41 (38%) infants whose mothers were diagnosed before delivery, it is probable
that most were infected in utero, around 20% intrapartum and 20% through
breastfeeding. Timing of transmission was unknown for most children of
undiagnosed mothers. For infants born to diagnosed women, the most common
contributing factors for transmission were difficulties with engagement and/or
antiretroviral therapy (ART) adherence in pregnancy (14 of 41) and late antenatal
booking (nine of 41); for the 67 children with undiagnosed mothers, these were
decline of HIV testing (28 of 67) and seroconversion (23 of 67). Adverse social
circumstances around the time of pregnancy were reported for 53% of women,
including uncertain immigration status, housing problems and intimate partner
violence. Eight children died, all born to undiagnosed mothers. CONCLUSIONS:
Priority areas requiring improvement include reducing incident infections,
improving ART adherence and facilitating better engagement in care, with
attention to addressing the health inequalities and adverse social situations
faced by these women.
PMID- 29336509
TI - The investigation of substituent effects on the fragmentation pathways of
pentacoordinated phenoxyspirophosphoranes by ESI-MSn.
AB - The fragmentation pathways of pentacoordinated phenoxyspirophosphoranes were
investigated in the positive mode by electrospray ionization multistage mass
spectrometry. The results demonstrate that the sodium adducts of the title
compounds undergo two competitive fragmentation pathways, and the fragmentation
patterns are heavily dependent on the various substituent patterns at the
phenolic group. An electron-withdrawing substituent at the ortho-position always
results in the removal of a corresponding phenol analogue, while cleavage by
spiroring opening becomes the predominant fragmentation pathway if an electron
donating substituent is at the phenolic group. The substituent effects on the
competitive fragmentation pathways were further elucidated by theoretical
calculations, single crystal structure analysis, and high-resolution mass
spectrometry. The results contribute to the understanding of the gas-phase
fragmentation reactions and the structure identification of spirophosphorane
analogues by electrospray ionization multistage mass spectrometry.
PMID- 29336510
TI - Hierarchy of Asymmetry at Work: Chain-Dependent Helix-to-Helix Interactions in
Supramolecular Polymers.
AB - A detailed investigation of the hierarchy of asymmetry operating in the self
assembly of achiral (1) and chiral ((S)-2 and (R)-3) 1,3,5
triphenylbenzenetricarboxamides (TPBAs) is reported. The aggregation of these
TPBAs is conditioned by the point chirality at the peripheral side chains for (S)
2 and (R)-3. An efficient helix-to-helix interaction that goes further in the
organization of fibrillar bundles is experimentally detected and theoretically
supported only for the achiral TPBA 1. The effective interdigitation of the
achiral aliphatic side chains produces a social self-sorting to form
preferentially heterochiral macromolecular aggregates.
PMID- 29336511
TI - Differential visual ornamentation between brood parasitic and parental cuckoos.
AB - The evolution of brood parasitism should affect adult phenotypic traits due to
sexual selection as well as the parasite-host interactions, although it is rarely
focused on. Sexual selection theory predicts extravagant secondary sexual
characteristics in brood parasites whereas immature-like modest sexual
characteristics in parental species. This is because juvenile-like immature
traits can attract mates by exploiting parental care for young (i.e. attraction
to young), and because the good parent process, which favours traits that signal
parental care ability, would constrain the evolution of costly secondary sexual
characteristics due to evolutionary trade-offs between parental investment and
sexually selected traits. Using a phylogenetic comparative approach, we studied
plumage and bare-part characteristics of adults in relation to brood parasitism
in cuckoos (family Cuculidae), in which brood parasitism together with loss of
parental care has evolved three times. As predicted, we found that nonparasitic
cuckoos had plumage more similar to the juveniles than did brood parasitic
cuckoos. Furthermore, nonparasitic cuckoos had a higher probability of having
additional bare skin, that is a seemingly less costly, hatchling-like trait, than
did brood parasitic cuckoos. This finding further supports the link between
parental care and sexual selection, although the influence of a parasite-host
interaction cannot be excluded. The analysis of evolutionary pathways suggested
interdependent evolution of additional bare skin and brood parasitism. Brood
parasitism together with the loss of parental care may prevent the maintenance of
a modest phenotype similar to the young, and vice versa in some cases.
PMID- 29336512
TI - Using field data to quantify chemical impacts on wildlife population viability.
AB - Environmental pollution is an important driver of biodiversity loss. Yet, to
date, the effects of chemical exposure on wildlife populations have been
quantified for only a few species, mainly due to a lack of appropriate laboratory
data to quantify chemical impacts on vital rates. In this study, we developed a
method to quantify the effects of toxicant exposure on wildlife population
persistence based on field monitoring data. We established field-based vital-rate
response functions for toxicants, using quantile regression to correct for the
influences of confounding factors on the vital rates observed, and combined the
response curves with population viability modelling. We then applied the method
to quantify the impact of DDE on three bird species: the White-tailed Eagle, Bald
Eagle, and Osprey. Population viability was expressed via five population
extinction vulnerability metrics: population growth rate (r1 ), critical patch
size (CPS), minimum viable population size (MVP), probability of population
extirpation (PE), and median time to population extirpation (MTE). We found that
past DDE exposure concentrations increased population extirpation vulnerabilities
of all three bird species. For example, at DDE concentrations of 25 mg/kg wet
mass of egg (the maximum historic exposure concentration reported in literature
for the Osprey), r1 became small (White-tailed Eagle and Osprey) or close to zero
(Bald Eagle), the CPS increased up to almost the size of Connecticut (White
tailed Eagle and Osprey) or West Virginia (Bald Eagle), the MVP increased up to
approximately 90 (White-tailed Eagle and Osprey) or 180 breeding pairs (Bald
Eagle), the PE increased up to almost certain extirpation (Bald Eagle) or only
slightly elevated levels (White-tailed Eagle and Osprey) and the MTE became
within decades (Bald Eagle) or remained longer than a millennium (White-tailed
Eagle and Osprey). Our study provides a method to derive species-specific field
based response curves of toxicant exposure, which can be used to assess
population extinction vulnerabilities and obtain critical levels of toxicant
exposure based on maximum permissible effect levels. This may help conservation
managers to better design appropriate habitat restoration and population recovery
measures, such as reducing toxicant levels, increasing the area of suitable
habitat or reintroducing individuals.
PMID- 29336513
TI - Palladium-Catalyzed Asymmetric Aminohydroxylation of 1,3-Dienes.
AB - A PdII -catalyzed asymmetric aminohydroxylation of 1,3-dienes with N-tosyl-2
aminophenols was developed by making use of a chiral pyridinebis(oxazoline)
ligand. The highly regioselective reaction provides direct and efficient access
to chiral 3,4-dihydro-2H-1,4-benzoxazines in high yield and enantioselectivity
(up to 96:4 e.r.). The reaction employs readily available N-tosyl-2-aminophenols
as a unique aminohydroxylation reagent and is complementary to known asymmetric
aminohydroxylation methods.
PMID- 29336514
TI - Machine-learned analysis of quantitative sensory testing responses to noxious
cold stimulation in healthy subjects.
AB - BACKGROUND: Pain in response to noxious cold has a complex molecular background
probably involving several types of sensors. A recent observation has been the
multimodal distribution of human cold pain thresholds. This study aimed at
analysing reproducibility and stability of this observation and further
exploration of data patterns supporting a complex background. METHOD: Pain
thresholds to noxious cold stimuli (range 32-0 degrees C, tonic: temperature
decrease -1 degrees C/s, phasic: temperature decrease -8 degrees C/s) were
acquired in 148 healthy volunteers. The probability density distribution was
analysed using machine-learning derived methods implemented as Gaussian mixture
modeling (GMM), emergent self-organizing maps and self-organizing swarms of data
agents. RESULTS: The probability density function of pain responses was trimodal
(mean thresholds at 25.9, 18.4 and 8.0 degrees C for tonic and 24.5, 18.1 and
7.5 degrees C for phasic stimuli). Subjects' association with Gaussian modes was
consistent between both types of stimuli (weighted Cohen's kappa = 0.91).
Patterns emerging in self-organizing neuronal maps and swarms could be associated
with different trends towards decreasing cold pain sensitivity in different
Gaussian modes. On self-organizing maps, the third Gaussian mode emerged as
particularly distinct. CONCLUSION: Thresholds at, roughly, 25 and 18 degrees C
agree with known working temperatures of TRPM8 and TRPA1 ion channels,
respectively, and hint at relative local dominance of either channel in
respective subjects. Data patterns suggest involvement of further distinct
mechanisms in cold pain perception at lower temperatures. Findings support data
science approaches to identify biologically plausible hints at complex molecular
mechanisms underlying human pain phenotypes. SIGNIFICANCE: Sensitivity to pain is
heterogeneous. Data-driven computational research approaches allow the
identification of subgroups of subjects with a distinct pattern of sensitivity to
cold stimuli. The subgroups are reproducible with different types of noxious cold
stimuli. Subgroups show pattern that hints at distinct and inter-individually
different types of the underlying molecular background.
PMID- 29336515
TI - Expectations and experiences of patients with osteoarthritis undergoing total
joint arthroplasty: An integrative review.
AB - BACKGROUND: The effectiveness of educational interventions for osteoarthritic
patients undergoing total joint arthroplasty remains inconclusive. It is
essential to understand the educational needs of these patients from their
perspectives. AIM: The aim of this study was to systematically summarize and
synthesize osteoarthritic patients' expectations and experiences in undergoing
total joint arthroplasty to identify their educational needs. DESIGN: An
integrative review was conducted. METHODS: Twenty studies (13 qualitative and 7
quantitative), published between 2006 and 2016, were independently appraised by 2
reviewers using the Critical Appraisal Skills Programme checklist for qualitative
studies and the Joanna Briggs Institute Critical Appraisal Tools for quantitative
studies. Data were analysed using thematic analysis, and the findings were
synthesized in a narrative summary. RESULTS: Six themes describing patients'
preoperative and post-operative educational needs were identified: (1)
preoperative anxiety, (2) unrealistic expectations of recovery, (3) post
operative pain, (4) regaining functional abilities, (5) physical and
psychological sense of loss, and (6) lack of continuity of care. CONCLUSION: This
review is the first to capture the osteoarthritic patients' educational needs
from their perspectives. The biopsychosocial model can address the
multidimensionality (biological, psychological, and social) of patients'
educational needs. A robust infrastructure supporting interprofessional
collaborative practice and continuity of care should be adopted to enhance
current educational efforts.
PMID- 29336516
TI - Neglect of attention to reproductive health in women with HIV infection:
contraceptive use and unintended pregnancies in the Swiss HIV Cohort Study.
AB - OBJECTIVES: Women with HIV infection are mainly of reproductive age and need
safe, effective and affordable contraception to avoid unintended pregnancies. The
aim of this study was to evaluate contraceptive use and unintended pregnancies in
this population in Switzerland. METHODS: A self-report anonymous questionnaire on
contraceptive methods, adherence to them, and unintended pregnancies was
completed by women included in the Swiss HIV Cohort Study (SHCS) between November
2013 and June 2014. Sociodemographic characteristics and information related to
combined antiretroviral therapy and HIV disease status were obtained from the
SHCS database. RESULTS: Of 462 women included, 164 (35.5%) reported not using any
contraception. Among these, 65 (39.6%) reported being sexually active, although
29 (44.6%) were not planning a pregnancy. Of 298 women using contraception, the
following methods were reported: condoms, 219 (73.5%); oral hormonal
contraception, 32 (10.7%); and intrauterine devices, 28 (9.4%). Among all women
on contraception, 32 (10.7%) reported using more than one contraceptive method
and 48 (16%) had an unintended pregnancy while on contraception (18, condoms; 16,
oral contraception; four, other methods). Of these, 68.1% terminated the
pregnancy and almost half (43.7%) continued using the same contraceptive method
after the event. CONCLUSIONS: Family planning needs in HIV-positive women are not
fully addressed because male condoms remained the predominant reported
contraceptive method, with a high rate of unintended pregnancies. It is of utmost
importance to provide effective contraception such as long-acting reversible
contraceptives for women living with HIV.
PMID- 29336518
TI - Seeded Polymerization through the Interplay of Folding and Aggregation of an
Amino-Acid-based Diamide.
AB - Amino acid based diamides are widely used as a substructure in supramolecular
polymers and are also key components of polypeptides that help to understand
protein folding. The interplay of folding and aggregation of a diamide was used
to achieve seed-initiated supramolecular polymerization. For that purpose, a
pyrene-substituted diamide was synthesized in which pyrene is used as a tracer to
monitor the supramolecular polymerization. Thermodynamics and time-dependent
studies revealed that the folding of the diamide moiety, via the formation of
intramolecular hydrogen bonds, effectively prevents a spontaneous nucleation that
leads to supramolecular polymerization. Under such out-of-equilibrium conditions,
the addition of seeds successfully initiates the supramolecular polymerization.
These results demonstrate the utility of such amino acid based diamides in
programmable supramolecular polymerizations.
PMID- 29336517
TI - Environmental Sequencing Fills the Gap Between Parasitic Haplosporidians and Free
living Giant Amoebae.
AB - Class Ascetosporea (Rhizaria; Endomyxa) comprises many parasites of
invertebrates. Within this group, recent group-specific environmental DNA (eDNA)
studies have contributed to the establishment of the new order Mikrocytida, a new
phylogeny and characterization of Paramyxida, and illuminated the diversity and
distribution of haplosporidians. Here, we use general and lineage-specific PCR
primers to investigate the phylogenetic "gap" between haplosporidians and their
closest known free-living relatives, the testate amoeba Gromia and reticulate
amoeba Filoreta. Within this gap are Paradinium spp. parasites of copepods, which
we show to be highly diverse and widely distributed in planktonic and benthic
samples. We reveal a robustly supported radiation of parasites, ENDO-3, comprised
of Paradinium and three further clades (ENDO-3a, ENDO-3b and SPP). A further
environmental group, ENDO-2, perhaps comprising several clades, branches between
this radiation and the free-living amoebae. Early diverging haplosporidians were
also amplified, often associated with bivalves or deep-sea samples. The general
primer approach amplified an overlapping set of novel lineages within ENDO-3 and
Haplosporida, whereas the group-specific primer strategy, targeted to amplify
from the earliest known divergent haplosporidians to Gromia, generated greater
sequence diversity across part of this phylogenetic range.
PMID- 29336519
TI - Management of venous thromboembolism: Time to measure our performance.
PMID- 29336520
TI - Near-Infrared Triggered Decomposition of Nanocapsules with High Tumor
Accumulation and Stimuli Responsive Fast Elimination.
AB - A near-infrared (NIR) induced decomposable polymer nanocapsule is demonstrated.
The nanocapsules are fabricated based on layer-by-layer co-assembly of azobenzene
functionalized polymers and up/downconversion nanoparticles (U/DCNPs). When the
nanocapsules are exposed to 980 nm light, ultraviolet/visible photons emitted by
the U/DCNPs can trigger the photoisomerization of azobenzene groups in the
framework. The nanocapsules could decompose from large-sized nanocapsule to small
U/DCNPs. Owing to their optimized original size (ca. 180 nm), the nanocapsules
can effectively avoid biological barriers, provide a long blood circulation (ca.
5 h, half-life time) and achieve four-fold tumor accumulation. It can fast
eliminate from tumor within one hour and release the loaded drugs for
chemotherapy after NIR-induced dissociation from initial 180 nm capsules to small
20 nm U/DCNPs.
PMID- 29336521
TI - Identification and quantification of VOCs by proton transfer reaction time of
flight mass spectrometry: An experimental workflow for the optimization of
specificity, sensitivity, and accuracy.
AB - Proton transfer reaction time of flight mass spectrometry (PTR-ToF-MS) is a
direct injection MS technique, allowing for the sensitive and real-time
detection, identification, and quantification of volatile organic compounds. When
aiming to employ PTR-ToF-MS for targeted volatile organic compound analysis, some
methodological questions must be addressed, such as the need to correctly
identify product ions, or evaluating the quantitation accuracy. This work
proposes a workflow for PTR-ToF-MS method development, addressing the main issues
affecting the reliable identification and quantification of target compounds. We
determined the fragmentation patterns of 13 selected compounds (aldehydes, fatty
acids, phenols). Experiments were conducted under breath-relevant conditions
(100% humid air), and within an extended range of reduced electric field values
(E/N = 48-144 Td), obtained by changing drift tube voltage. Reactivity was
inspected using H3 O+ , NO+ , and O2+ as primary ions. The results show that a
relatively low (<90 Td) E/N often permits to reduce fragmentation enhancing
sensitivity and identification capabilities, particularly in the case of
aldehydes using NO+ , where a 4-fold increase in sensitivity is obtained by means
of drift voltage reduction. We developed a novel calibration methodology, relying
on diffusion tubes used as gravimetric standards. For each of the tested
compounds, it was possible to define suitable conditions whereby experimental
error, defined as difference between gravimetric measurements and calculated
concentrations, was 8% or lower.
PMID- 29336522
TI - Continued root maturation despite persistent apical periodontitis of immature
permanent teeth after failed regenerative endodontic therapy.
AB - Three immature permanent teeth with pulp necrosis and apical periodontitis were
treated with regenerative endodontic therapy (RET), which included root canal
disinfection with sodium hypochlorite irrigation, intra-canal medication with
calcium hydroxide paste, 17% EDTA rinse, induction of periapical bleeding into
the canal, collagen matrix and MTA coronal seal, and composite resin restoration
of access cavities. After different periods of follow-up, it was observed that
continued root maturation, especially apical closure occurred despite persistent
apical periodontitis of immature permanent teeth after failed RET. This finding
is of interest as the secondary goal of further root maturation occurred despite
failure of the primary goal of elimination of clinical symptom/sign and
periapical inflammation. The possible biological mechanisms that could allow for
further root maturation to occur in spite of persistent root canal infection of
immature permanent teeth are discussed. Based on these observations, the biology
of wound healing of immature permanent teeth after injury is not fully understood
and should be further investigated. This case report demonstrates that whilst
further root maturation is considered a successful outcome for teeth treated with
RET, the primary objective must be the resolution of the signs and symptoms of
apical periodontitis.
PMID- 29336523
TI - Quadratus lumborum block in management of severe pain after uterine artery
embolization.
AB - BACKGROUND AND OBJECTIVES: The quadratus lumborum (QL) block has been widely used
for acute postoperative pain management after numerous surgical procedures
including urological, abdominal, gynaecological and orthopaedic surgical
procedures. The local anaesthetic spread in this area can provide unilateral
sensory block in T6-L2 dermatomes. We performed bilateral quadratus lumborum
block for the management of acute pain after the uterine artery embolization
(UAE). METHODS: A 43-year-old woman was admitted to the gynaecology department of
Mother and Child Hospital, University Medical Center, for uterine artery
embolization. Shortly, after successful completion of the UAE procedure, the
patient began to complain of severe pain in the lower abdomen rated as a 9 on a
verbal analogue scale (VAS) of 0-10. Intravenous tramadol 100 mg was infused over
30 min with minimal reduction in pain. Trimeperidine 20 mg was then infused over
30 min. Pain scores, however, remained 7-8/10 on the VAS. It was therefore
decided to place a bilateral single-shot ultrasound-guided quadratus lumborum
block. RESULTS: The procedure was well tolerated and brought notable pain relief.
VAS declined from 8/10 to 5/10 after 30 min and to 3/10 at 60 min. Over the
ensuing 24 h, VAS pain intensity remained 2-3/10. No further analgesics were
necessary. CONCLUSION: A randomized control clinical trial is warranted to assess
the efficacy of QL blockade and to compare it with other analgesic options in
uterine artery embolization. Bilateral quadratus lumborum blockade may be an
excellent pain control option after uterine artery embolization. SIGNIFICANCE:
Uterine artery embolization is associated with significant postprocedural pain
which can prove difficult to manage with opioids. Bilateral quadratus lumborum
block may be an excellent pain control option - one that might significantly
reduce not only pain, but also the need for opioids and perhaps even the need for
hospitalization.
PMID- 29336524
TI - Human Intestinal Dendritic Cells in Inflammatory Bowel Diseases.
AB - Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative
colitis, is a serious, costly, and persistent health problem with an estimated
prevalence in Western countries around 0.5% of the general population; its
socioeconomic impact is comparable with that for chronic diseases such as
diabetes. Conventional treatment involves escalating drug regimens with
concomitant side effects followed, in some cases, by surgical interventions,
which are often multiple, mainly in Crohn's disease. The goal of finding a
targeted gut-specific immunotherapy for IBD patients is therefore an important
unmet need. However, to achieve this goal we first must understand how dendritic
cells (DC), the most potent antigen present cells of the immune system, control
the immune tolerance in the gastrointestinal tract and how their properties are
altered in those patients suffering from IBD. In this review, we summarize the
current available information regarding human intestinal DC subsets composition,
phenotype, and function in the human gastrointestinal tract describing how, in
the IBD mucosa, DC display pro-inflammatory properties, which drive disease
progression. A better understanding of the mechanisms inducing DC abnormal
profile in IBD may provide us with novel tools to perform tissue specific
immunomodulation.
PMID- 29336525
TI - Complications of curative radiation treatment for early prostate cancer.
AB - AIM: To report the incidence of urological complications following curative
radiation treatment for early prostate cancer, including minimally invasive
urological procedures (MUIP), hospital admissions and open surgical procedures.
Second malignancies following radiation are also reported and compared with
patients undergoing a prostatectomy. METHODS: Included were patients receiving
curative intent external beam radiation treatment for early prostate cancer
between January 1, 2002, and December 31, 2009. Medical records were reviewed for
baseline characteristics, treatment details and outcomes. Kaplan-Meier methods
were used to derive the 5-year cumulative incidence of the urological outcomes
and second malignancy. RESULTS: There were 439 patients identified. The median
follow-up was 6.96 years. The median age was 69. A total of 56 patients developed
a radiation related urological complication, 25 requiring hospital admission. The
5-year cumulative incidence for an MIUP and admission was 3.95% (95% confidence
interval (CI), 2.47-6.28) and 2.24% (95% CI, 1.17-4.27), respectively. There were
no open surgical procedures. Further malignancy developed in 27 patients during
the 5- to 9-year posttreatment period with a cumulative incidence of 10.7% (95%
CI, 7.31-15.51). Of the comparator prostatectomy group, of the 265 eligible
patients analyzed, 19 patients developed a second malignancy with a cumulative
incidence of 9.92% (95% CI, 6.28-15.48). On log-rank testing, there was no
difference in the cumulative incidence rates of second malignancy between 5 and 9
years, following respective treatments (P = 0.8554). CONCLUSIONS: The incidence
of MUIP, hospital admissions and open surgical procedures following radiation is
reassuringly low. The second malignancy rates are also low and similar to the
rates in patients treated with a prostatectomy.
PMID- 29336526
TI - Human Milk Oligosaccharides as Promising Antivirals.
AB - Human milk oligosaccharides (HMOs) are diverse unconjugated carbohydrates that
are highly abundant in human breast milk. These glycans are investigated in the
context of exhibiting multiple functions in infant growth and development. They
seem to provide protection against infectious diseases, including a number of
poorly manageable viral infections. Although the potential mechanism of the HMO
antiviral protection is rather broad, much of the current experimental work has
focused on studying of HMO antiadhesive properties. HMOs may mimic structures of
viral receptors and block adherence to target cells, thus preventing infection.
Still, the potential of HMOs as a source for new antiviral drugs is relatively
unexploited. This can be partly attributed to the extreme complexity of the virus
carbohydrate interactions and technical difficulties in HMO isolation,
characterization, and manufacturing procedures. Fortunately, we are currently
entering a period of major technological advances that have enabled deeper
insights into carbohydrate mediated viral entry, rational selection of HMOs as
anti-entry inhibitors, and even evaluation of individual synthetic HMO
structures. Here, we provide an up-to-date review on glycan binding studies for
rotaviruses, noroviruses, influenza viruses, and human immunodeficiency viruses.
We also discuss the preventive and therapeutic potential of HMOs as anti-entry
inhibitors and address challenges on the route from fundamental studies to
clinical trials.
PMID- 29336527
TI - Sustainable Synthesis of Oxalic and Succinic Acid through Aerobic Oxidation of C6
Polyols Under Mild Conditions.
AB - The sustainable chemical industry encompasses a shift from the use of fossil
carbon to renewable carbon. The synthesis of chemicals from nonedible biomass
(cellulosic or oil) represents one of the key steps for "greening" the chemical
industry. In this paper, we report the aerobic oxidative cleavage of C6 polyols
(5-HMF, glucose, fructose and sucrose) to oxalic acid (OA) and succinic acid (SA)
in water under mild conditions using M@CNT and M@NCNT (M=Fe, V; CNT=carbon
nanotubes; NCNT=N-doped CNT), which, under suitable conditions, were recoverable
and reusable without any loss of efficiency. The influence of the temperature, O2
pressure (PO2 ), reaction time and stirring rate are discussed and the best
reaction conditions are determined for an almost complete conversion of the
starting material and a good OA yield of 48 %. SA and formic acid were the only
co-products. The former could be further converted into OA by oxidation in the
presence of formic acid, resulting in an overall OA yield of >62 %. This process
was clean and did not produce organic waste nor gas emissions.
PMID- 29336528
TI - Synthesis of Functionalized (eta5 -Indenyl)rhodium(III) Complexes and Their
Application to C-H Bond Functionalization.
AB - It has been established that reductive complexation of functionalized
benzofulvenes, which are readily prepared from commercially available indene and
2-methylindene, with RhCl3 in ethanol affords the corresponding indenyl
rhodium(III) dichlorides bearing substituents at the 1- (H or CO2 Et), 2- (H or
Me), and 3- [CH2 Ph or CH2 (2-MeOC6 H4 )] positions. The indenyl-rhodium(III)
complexes bearing one ethoxycarbonyl group showed higher thermal stability and
regioselectivity than our previously reported CpE RhIII complex toward the
oxidative [3+2] annulation of acetanilides with internal alkynes.
PMID- 29336529
TI - High prevalence of reduced thrombin generation and/or decreased platelet response
in women with unexplained heavy menstrual bleeding.
AB - INTRODUCTION: Heavy menstrual bleeding (HMB) is a condition that affects 20%-30%
of women of reproductive age. HMB has a multifactorial pathophysiology, which is
incompletely understood. HMB symptoms are very common in patients with
established haemostasis defects, likewise, women with heavy menstrual bleeding
have a higher prevalence of impaired Von Willebrand factor (VWF) levels and
function, thrombocytopenia, impaired platelet function and impaired coagulation.
The aim of this study was to quantify the prevalence of impaired platelet
function, impaired coagulation and reduced VWF activity in patients with HMB.
METHODS: We have used thrombin generation (TG), a flow cytometry-based platelet
function test and a flow cytometry-based VWF function test to study haemostasis
in 58 women (median age: 48.4 years, range 40-60 years) with HMB. In addition, we
determined VWF antigen levels and VWF ristocetin co-factor activity in platelet
poor plasma. Reference ranges of platelet function were measured in whole blood
of 123 healthy volunteers, while reference ranges of TG were determined in
platelet-poor plasma (PPP) of 126 healthy volunteers. RESULTS: Fourteen (24%)
patients with HMB had impaired platelet function and 17 (29.3%) patients had
impaired coagulation. Five patients (8.6%) had both impaired platelet function
and impaired coagulation. Only 2 (3.4%) patients had an impaired VWF function or
levels; one of them was in combination with impaired coagulation. CONCLUSION: Our
approach in women with HMB using a high precision platelet function test in
combination with thrombin generation showed impaired coagulation or impaired
platelet function in more than 40% of the patients.
PMID- 29336530
TI - Cut-point for Ki-67 proliferation index as a prognostic marker for glioblastoma.
AB - INTRODUCTION: Ki-67 proliferation index (Ki-67 index) is used to quantify cell
proliferation during histopathological assessment of various tumors including
glioblastoma (GB). AIM: We aimed to assess correlation between Ki-67 index and
overall survival in patients with GB and determine a cut-point for Ki-67 index
that predicts for poorer survival. METHOD: Records of adult patients diagnosed
with GB on histopathological specimens at a tertiary cancer center in Sydney
between 1 January 2002 and 30 July 2012 were retrieved. Specimens of these
patients were examined for quantification of Ki-67 staining by two independent
pathologists. Patient, disease, treatment, and survival data were collected from
hospital and cancer care service records. Statistical analysis was performed
using proportional hazards models, Kaplan-Meier curves, and the minimum P-value
approach. RESULT: Of the eligible 71 patients, 58% were males with median age of
58 (range 18-87). Seventy-three percent of patients were of ECOG performance
status 0-1. There was a statistically significant correlation between Ki-67 index
and overall survival. In patients with Ki-67 > 22% (n = 36), 5-year survival was
approximately 30% compared to 5% in those with Ki-67 <= 22% (n = 35; log-rank P
value = 0.04; hazard ratio (HR) = 0.53; 95% confidence intervals (CI), 0.29
0.97). CONCLUSION: This study demonstrates a positive correlation between Ki-67
index and overall survival in patients with GB. Percentage staining of Ki-67 <
22% appears to predict for poorer survival in GB.
PMID- 29336531
TI - Nanobiotechnology of Carbon Dots: A Review.
AB - In recent years, carbon dots (CDs) have gained increasing attention owing to
their unique properties and enormous potential for several biomedical and
technological applications. CDs are biocompatible, have a small size with a
relatively large surface area, are photostable, and have customizable
photoluminescence properties. This review is divided into the following
discussions of CDs: general definitions; an overview of recent reviews; methods
of green and classical synthesis; applications in bioimaging, involving
supercapacitors, nanocarriers and nanomedicine; toxicological evaluations
(including cytotoxic, genotoxic and anti-cancer properties of CDs); their
conjugation with enzymes, biosensors, and cell labeling. Finally the remaining
drawbacks and challenges of CD applications are highlighted. In this context,
this article aims to provide critical insight and inspire further developments in
the synthesis and application of CDs.
PMID- 29336532
TI - Nanoscale Photodynamic Agents for Colorectal Cancer Treatment: A Review.
AB - Colorectal cancer is the most common form of gastroenteric cancer worldwide.
Photodynamic therapy is emerging as an attractive method to treat cancers.
Candidate targets of photodynamic therapy include epidermal growth factor
receptors, cholesterol and low-density lipoprotein, estrogen receptors, the
nucleus and DNA, folic acid receptors, cholecystokinin A receptors, lectin
saccharide receptors, and tumor-specific antibodies. Specifically, in colorectal
tumors, anti-DR5 antibody and cancer-specific antibody moieties are involved.
Cancer cells incorporate greater quantities of sugars, and glycoconjugated
photosensitizer has remarkable internalization and cytotoxicity in
colon/colorectal cancer cells. Simultaneously, to circumvent the bio-distribution
limitation, other molecules, including lectins, Hyaluronic acid, and peptides,
have also been considered for colorectal cancer. Other novel strategies
indirectly targeting colorectal cancer include pH-responsive PS, enzymatically
activated photosensitization, and cancer-suppressing immune cells, mainly
macrophages. Recently, nanoparticles have gained attention as a versatile
platform for multi-functional photodynamic therapy. In this review, we summarize
the targeting strategies investigated and highlight the potential of
nanoparticles for target photodynamic therapy in colorectal cancer.
PMID- 29336533
TI - Targeted Nanocurcumin Therapy Using Annexin A2 Anitbody Improves Tumor
Accumulation and Therapeutic Efficacy Against Highly Metastatic Breast Cancer.
AB - A major challenge in pharmaceutical research is effective targeting strategies to
their sites of action. Emerging knowledge and the current progress in
nanotechnology based delivery systems has opened up exciting ways towards
successful targeted nanodelivery systems. For cancer therapy, nanoparticle-based
drug formulations hold several advantages over free drugs, including improved
pharmacokinetics, enhanced tumor accumulation, reduced systemic exposure and side
effects and better patient compliance. The goal of this study was to validate the
in vivo targeting potential and evaluate the combinatorial therapeutic potential
of novel Annexin A2 (AnxA2) antibody-conjugated curcumin loaded poly(lactic-co
glycolic acid) (PLGA) nanoparticles (AnxA2-CPNP) against metastatic breast
cancer. As a first step, we demonstrated that the cell-surface expression of
AnxA2 is increases during breast cancer progression with very high expression in
highly malignant cancer cells and basal expression in non-malignant cells. This
confirmed AnxA2 as an excellent target for targeting our curcumin nanoparticles.
Our results indicate that AnxA2-CPNP showed increased uptake in highly metastatic
breast cancer cells than untargeted nanoparticles due to the differential AnxA2
expression. Cell viability, plasmin generation and wound healing assays reveal
that AnxA2-CPNPs effectively inhibited cell proliferation, invasion and
migration, key elements for cancer growth and metastasis. Further, angiogenesis
assay illustrated that AnxA2-CPNPs decreased the formation of tube capillaries,
thus inhibiting neoangiogenesis, a critical element in tumor growth. Live animal
imaging demonstrated that AnxA2-PNPs and AnxA2-CPNPs effectively targeted and
accumulated in the tumor as seen by the increased fluorescence intensity on the
live scans. Xenograft studies in mice showed significant regression of breast
tumor as a result of both effective targeting, accumulation and sustained release
of curcumin in the tumor. In conclusion, AnxA2-CPNPs were successfully validated
for their breast tumor targeting potential and its improved therapeutic efficacy
against metastatic breast cancer.
PMID- 29336534
TI - Folic Acid Functionalized gamma-Cyclodextrin C60, A Novel Vehicle for Tumor
Targeted Drug Delivery.
AB - Folic acid (FA)-gamma cyclodextrin (gamma CD)-C60 was synthesized in this study
as a carrier for tumor-targeted drug delivery to enhance the anticancer effect of
carboplatin (CBP). FA-gamma CD and C60-CBP were prepared and C60-CBP was then
entrapped into FA-gamma CD through host-guest effect. FA-gamma CD-C60
significantly increased the intracellular uptake and release of CBP, thereby
providing higher cytotoxicity against the HeLa cells with high expression of
folate receptor (FR). In vivo experiments revealed that FA-gamma CD-C60-CBP had
more significant anticancer effects than CBP alone, showing no obvious toxic
effects on zebrafish at concentration as high as 500 MUg/mL. These results
suggest that FA-gamma CD-C60 may provide an effective strategy for administration
of antineoplastics, with great promise in future targeted therapy for cancers.
PMID- 29336536
TI - Imprecise Percentages.
PMID- 29336535
TI - Construction of Functional Targeting Daunorubicin Liposomes Used for Eliminating
Brain Glioma and Glioma Stem Cells.
AB - The highly infiltrative nature of brain glioma makes total surgical removal of
cancerous cells virtually impossible. Regular chemotherapy plays an important
role in eradicating the residual cancer cells but is ineffective in treating
brain glioma due to the hindrance of drug penetration into the tumor site by the
blood brain barrier (BBB) and the regeneration of cancer cells by glioma stem
cells (GSCs). In this study, functional targeting daunorubicin liposomes were
developed by modifying the liposomes with distearoylphosphatidylethanolamine
polyethylene glycol-polyethylenimine (DSPE-PEG2000PEI600 and a lipid-glucose
derivative (DSPE-PEG2000-GLU). The studies were performed in brain glioma and
glioma stem cells in vitro and in brain glioma-bearing mice inoculated with the
glioma stem cells. The results showed that the functional targeting daunorubicin
liposomes were able to significantly transfer across the BBB and exhibited an
obvious efficacy in killing glioma and glioma stem cells in mice. The action
mechanisms of the functional targeting daunorubicin liposomes were related to
their properties: long-duration circulation in the blood system, transport
capability across the BBB, concentrated accumulation in the brain glioma site,
and increased internalization by malignant cells and their mitochondria. This
functional drug formulation showed anticancer efficacy through a direct cytotoxic
effect and an apoptosis-inducing effect through the apoptotic signaling pathways
in the cytoplasm and mitochondria of the cells. As a chemotherapy strategy for
treating brain glioma, functional targeting daunorubicin liposomes have the
potential to eliminate brain glioma along with glioma stem cells.
PMID- 29336538
TI - Error in Abstract.
PMID- 29336537
TI - Polymer-Encapsulated Abeta Peptide Fragments as an Oligomeric-Specific Vaccine
for Alzheimer's Disease.
AB - Vaccination is regarded as one of the most cost-effective and reliable methods
for combating disease. We have developed a new method for an oligomeric Abeta
specific AD vaccination using polymer micelle-encapsulated peptide fragments,
which overcome many problems of vaccination associated with the direct use of the
Abeta1-42 peptide. We studied different encapsulated forms of shortened Abeta
peptides with and without the entire T cell epitope in an APP/PS1 mouse model.
After two inoculations with encapsulated Abeta fragments, antibodies were
produced in all mice with antibody titer greater than 1:12,800. No anti-polymer
antibodies were detected after five inoculations, and none of the injected mice
showed any adverse effects throughout experimentation. Anti-Abeta antibodies from
our polymer-encapsulated vaccine were able to bind to A plaques in the brain of
our mice, and were able to specifically recognize oligomeric Abeta. Our results
suggest that the safety and efficacy issues previously encountered in other Abeta
vaccination trials may be successfully addressed by using micelle-encapsulated
peptides. These shorter Abeta fragments are also easier to synthesize and more
cost-effective than the highly hydrophobic full-length Abeta1-42 peptide.
PMID- 29336539
TI - Chitosan-Coated Poly(lactic-co-glycolic acid)-Diiodinated boron-Dipyrromethene
Nanoparticles Improve Tumor Selectivity and Stealth Properties in Photodynamic
Cancer Therapy.
AB - Their limited solubility and lack of tumor selectivity limit the clinical
usefulness of photosensitizers. Various nanostructures have been evaluated as
delivery agents for photosensitizers in an attempt to overcome these obstacles,
but these have typically been limited by premature clearance by the
reticuloendothelial system (RES) and non-specific interactions with normal cells
that result from their hydrophobic surfaces. In this study, we report our attempt
to circumvent these problems by applying a low molecular weight chitosan (25 kDa)
coating to a poly(lactic-co-glycolic acid)-diiodinated boron dipyrromethene (PLGA
I2BODIPY) nanoparticle-photosensitizer construct. This chitosan coating increased
the hydrophilicity and decreased the charge of PLGA-I2 BODIPY nanoparticle
surfaces without changing their size (average diameter 147 nm) or morphology. In
comparison to the uncoated controls, the coated nanoparticles reduced the burst
release of I2BODIPY, increased its predominantly lysosomal cellular uptake, and
enhanced its photocytotoxicity in 4T1 murine and MDA-MB-231 human breast cancer
cells. PLGA-Chitosan-I2BODIPY nanoparticles also showed reduced serum protein
adsorption and macrophage uptake compared to the uncoated controls. In 4T1 tumor
bearing mice, the PLGA-Chitosan-I2BODIPY nanoparticles exhibited better tumor
targeting selectivity and significantly reduced accumulation in RES tissues,
including the lymph nodes, spleen and liver (by 10.2-, 2.1- and 1.3-fold,
respectively), and in non-tumorous organs, such as the skin and eyes (by 22.7-
and 4-fold, respectively). The PLGA-Chitosan-I2BODIPY and PLGA-I2BODIPY
nanoparticles also showed increased anticancer efficacy compared to free
I2BODIPY. These results suggest that the low molecular weight chitosan (25 kDa)
is a promising nanoparticle "stealth coating" that improves tumor selectivity.
PMID- 29336540
TI - Silicene on Monolayer PtSe2: From Strong to Weak Binding via NH3 Intercalation.
AB - We study the properties of silicene on monolayer PtSe2 by first-principles
calculations and demonstrate a much stronger interlayer interaction than
previously reported for silicene on other semiconducting substrates. This fact
opens the possibility of a direct growth. A band gap of 165 meV results from
inversion symmetry breaking and large spin-splittings in the valence and
conduction bands from proximity to monolayer PtSe2 and its strong spin-orbit
coupling. It is also shown that the interlayer interaction can be effectively
reduced by intercalating NH3 molecules between silicene and monolayer PtSe2
without inducing charge transfer or defect states near the Fermi energy. A small
NH3 diffusion barrier makes intercalation a viable experimental approach to
control the interlayer interaction.
PMID- 29336541
TI - Rapid Patterning of PDMS Microfluidic Device Wettability Using Syringe-Vacuum
Induced Segmented Flow in Nonplanar Geometry.
AB - We present a simple and rapid method to spatially pattern the surface wetting
properties of PDMS microfluidic devices by layer-by-layer (LbL) deposition of
polyelectrolytes using syringe-vacuum-induced segmented flow in nonplanar
geometry. Our technique offers selective surface modification in microfluidic
chips with multiple flow-focusing junctions, enabling production of monodisperse
double- and triple-emulsion drops.
PMID- 29336542
TI - Humidity-Sensing Performance of 3DOM WO3 with Controllable Structural
Modification.
AB - The development of humidity sensors with excellent sensing performance is a great
challenge in the field of material chemistry. Here, we synthesized 3DOM WO3
nanomaterials through a poly(methyl methacrylate) template method, and first, we
applied it to humidity measurement. For the goal of better sensing performance,
the structural modification of Li/K-codoping was adopted, and the test results
showed that Li/K-codoped 3DOM WO3 possessed highly improved humidity sensing
performances, such as high response, low-humidity hysteresis, good long-term
stability, great repeatability, decent response, and recovery properties. To
deeply understand the great effect of Li/K-codoping on sensing performance, the
pure, Li-monodoped, and Li/K-codoped 3DOM WO3-based humidity sensors were
compared, and we found that the structure defects and adsorbed oxygen as well as
the co-effect of Li/K dopants were key factors for the improved sensing
performance. Additionally, a possible humidity sensitive mechanism was proposed
to further study the promotion effect of Li/K-codoping on humidity sensing
process.
PMID- 29336543
TI - Histone Deacetylase 11 Is a Fatty-Acid Deacylase.
AB - Histone deacetylase 11 (HDAC11) is a sole member of the class IV HDAC subfamily
with negligible intrinsic deacetylation activity. Here, we report in vitro
profiling of HDAC11 deacylase activities, and our data unequivocally show that
the enzyme efficiently removes acyl moieties spanning 8-18 carbons from the side
chain nitrogen of the lysine residue of a peptidic substrate. Additionally, N
linked lipoic acid and biotin are removed by the enzyme, although with lower
efficacy. Catalytic efficiencies toward dodecanoylated and myristoylated peptides
were 77 700 and 149 000 M-1 s-1, respectively, making HDAC11 the most proficient
fatty-acid deacylase of the HDAC family. Interestingly, HDAC11 is strongly
inhibited by free myristic, palmitic, and stearic acids with inhibition constants
of 6.5, 0.9, and 1.6 MUM, respectively. At the same time, its deacylase activity
is stimulated more than 2.5-fold by both palmitoyl-coenzyme A and myristoyl
coenzyme A, pointing toward metabolic control of the enzymatic activity by fatty
acid metabolites. Our data reveal novel enzymatic activity of HDAC11 that can, in
turn, facilitate the uncovering of additional biological functions of the enzyme
as well as the design of isoform-specific HDAC inhibitors.
PMID- 29336544
TI - Identification of Collateral Sensitivity to Dihydroorotate Dehydrogenase
Inhibitors in Plasmodium falciparum.
AB - Drug resistance has been reported for every antimalarial in use highlighting the
need for new strategies to protect the efficacy of therapeutics in development.
We have previously shown that resistance can be suppressed with a population
biology trap: by identifying situations where resistance to one compound confers
hypersensitivity to another (collateral sensitivity), we can design combination
therapies that not only kill the parasite but also guide its evolution away from
resistance. We applied this concept to the Plasmodium falciparum dihydroorotate
dehydrogenase ( PfDHODH) enzyme, a well validated antimalarial target with
inhibitors in the development pipeline. Here, we report a high-throughput screen
to identify compounds specifically active against PfDHODH resistant mutants. We
additionally perform extensive cross-resistance profiling allowing us to identify
compound pairs demonstrating the potential for mutually incompatible resistance.
These combinations represent promising starting points for exploiting collateral
sensitivity to extend the useful lifespan of new antimalarial therapeutics.
PMID- 29336545
TI - Self-Assembly of Silicon@Oxidized Mesocarbon Microbeads Encapsulated in Carbon as
Anode Material for Lithium-Ion Batteries.
AB - The utilization of silicon/carbon composites as anode materials to replace the
commercial graphite is hampered by their tendency to huge volumetric expansion,
costly raw materials, and complex synthesis processes in lithium-ion batteries.
Herein, self-assembly method is successfully applied to prepare hierarchical
silicon nanoparticles@oxidized mesocarbon microbeads/carbon (Si@O-MCMB/C)
composites for the first time, in which O-MCMB core and low-cost sucrose-derived
carbon shell not only effectively enhance the electrical conductivity of the
anode, but also mediate the dramatic volume change of silicon during cycles. At
the same time, the carbon can act as "adhesive", which is crucial in enhancing
the adhesive force between Si and O-MCMB in the composites. The as-obtained Si@O
MCMB/C delivers an initial reversible capacity of 560 mAh g-1 at 0.1 A g-1, an
outstanding cyclic retention of 92.8% after 200 cycles, and respectable rate
capability. Furthermore, the synthetic route presented here is efficient, less
expensive, simple, and easy to scale up for high-performance composites.
PMID- 29336546
TI - CuAg@Ag Core-Shell Nanostructure Encapsulated by N-Doped Graphene as a High
Performance Catalyst for Oxygen Reduction Reaction.
AB - Development of a robust, cost-effective, and efficient catalyst is extremely
necessary for oxygen reduction reaction (ORR) in fuel cell applications. Herein,
we reported a well-defined nanostructured catalyst of highly dispersed CuAg@Ag
core-shell nanoparticle (NP)-encapsulated nitrogen-doped graphene nanosheets
(CuAg@Ag/N-GNS) exhibiting a superior catalytic activity toward ORR in alkaline
medium. The synergistic effects produced from the unique properties of CuAg@Ag
core-shell NPs and N-GNS made such a novel nanohybrid display a catalytic
behavior comparable to that of the commercial Pt/C product. In particular, it
demonstrated a much better stability and methanol tolerance than Pt/C under the
same conditions. Because of its outstanding electrochemical performance and ease
of synthesis, CuAg@Ag/N-GNS material was expected to be a promising low-cost
catalyst for ORR in alkaline fuel cell applications.
PMID- 29336547
TI - Efficient Blue and Yellow Organic Light-Emitting Diodes Enabled by Aggregation
Induced Emission.
AB - A new class of donor-bridge-acceptor (D-pi-A) pi-conjugated light-emitting
molecules comprising carbazole as donor and maleimide (Cbz-MI, Cbz-MI(d)),
phthalimide (Cbz-Pth) as acceptor units with phenyl ring as spacer have been
synthesized in good yields. These compounds exhibit high quantum yield with three
distinct emission colors yellowish-green (Cbz-MI), bright yellow Cbz-MI(d), and
sky blue (Cbz-Pth) in the solid state. Single-crystal X-ray and quantum chemical
calculations reveals that twisting of the phenyl rings with high torsional angle
on maleimide and phthalimide units reduce the effective inter-chromophore
electronic coupling, furnish dramatic changes in their photophysical properties
in solution and solid states. Intriguingly, Cbz-MI(d) and Cbz-Pth exhibits a
unique aggregation-induced blue-shifted emission (AIBSE) due to restricted
intramolecular rotation (RIR) process, while Cbz-MI shows red-shifted emission in
the solid state. The solvatochromic study reveal that combined RIR and excited
state migration augment AIE (aggregation-induced emission) properties. The
electrochemical properties reveal that Cbz-MI exhibits high oxidation propensity
while Cbz-Pth shows low reduction values. Subsequently, organic light-emitting
diodes (OLEDs) were fabricated with a simple three-layer device containing Cbz
Pth and Cbz-MI(d) as emitting layers. Cbz-MI(d) exhibits high performance yellow
OLED with an external quantum efficiency exceeding ~4.1% and a brightness
exceeding ~73915 cd/m2, which is among the best performance reported for bright
yellow fluorescence organic light-emitting diodes.
PMID- 29336548
TI - Judicious Design of Cationic, Cyclometalated Ir(III) Complexes for Photochemical
Energy Conversion and Optoelectronics.
AB - The exponential growth in published studies on phosphorescent metal complexes has
been triggered by their utilization in optoelectronics, solar energy conversion,
and biological labeling applications. Very recent breakthroughs in organic
photoredox transformations have further increased the research efforts dedicated
to discerning the inner workings and structure-property relationships of these
chromophores. Initially, the principal focus was on the Ru(II)-tris-diimine
complex family. However, the limited photostability and lack of luminescence
tunability discovered in these complexes prompted a broadening of the research to
include 5d transition metal ions. The resulting increase in ligand field
splitting prevents the population of antibonding eg* orbitals and widens the
energy range available for color tuning. Particular attention was given to
Ir(III), and its cyclometalated, cationic complexes have now replaced Ru(II) in
the vast majority of applications. At the start, this Account documents the
initial efforts dedicated to the color tuning of these complexes for their
application in light emitting electrochemical cells, an easy to fabricate single
layer organic light emitting device (OLED). Systematic modifications of the
ligand sphere of [Ir(ppy)2bpy]+ (ppy: 2-phenylpyridine, bpy: 2,2'-bipyridine)
with electron withdrawing and donating substituents allowed access to complexes
with luminescence emission maxima throughout the visible spectrum exhibiting room
temperature excited state lifetimes ranging from nanoseconds to dozens of
microseconds and quantum yields up to 15 times that of [Ru(bpy)3]2+. The diverse
photophysical properties were also beneficial when using these Ir(III) complexes
for driving solar fuel-producing reactions. For instance, photocatalytic water
reduction systems were explored to gain access to efficient water splitting
systems. For this purpose, a variety of water reduction catalysts were paired
with libraries of Ir(III) photosensitizers in high-throughput photoreactors. This
parallelized approach allowed exploration of the interplay between the diverse
photophysical properties of the Ir compounds and the electron-accepting
catalysts. Further work enhanced and simplified the critical electron transfer
processes between these two species through the use of bridging functional groups
installed on the photosensitizer. Later, a novel approach summarized in this
Account explores the possibility of using Zn metal as a solar fuel. Structure
activity relationships of the light-driven reduction of Zn2+ to Zn metal are
described. DFT calculations along with cyclic voltammetry were utilized to gain
clear insights into the complexes' electronic structures responsible for the
effective photochemical properties observed in these dyes. While [Ir(ppy)2bpy]+
and its derivatives were found to be much more photostable than the Ru(II)-tris
diimine complex family, mass spectrometry indicated that the bpy ligand still
photodissociated under extensive illumination. An interesting new approach
involved the substitution of the bidentate 2,2'-bipyridine with a stronger
chelating terpyridine ligand. This approach leaves room for one 2-phenylpyridine
ligand and a third, anionic ligand, either Cl- or CN-. This Account reviews the
effect of structural modifications on the photophysical properties of these
[Ir(tpy)(ppy)X]+ complexes and corroborates the findings with the results
obtained through DFT modeling. These complexes found application in
photocatalytic CO2 reductions as well as a solvent tolerant light-absorber for
the photogeneration of hydrogen. It was also documented that the robustness of
these dyes in photoredox processes supersedes those of the commercially available
[Ir(ppy)2(dtbbpy)]PF6 and [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 complexes pioneered in the
Bernhard laboratory.
PMID- 29336549
TI - Top-Down Hydrogen-Deuterium Exchange Analysis of Protein Structures Using
Ultraviolet Photodissociation.
AB - Top-down hydrogen-deuterium exchange (HDX) analysis using electron capture or
transfer dissociation Fourier transform mass spectrometry (FTMS) is a powerful
method for the analysis of secondary structure of proteins in solution. The
resolution of the method is a function of the degree of fragmentation of backbone
bonds in the proteins. While fragmentation is usually extensive near the N- and C
termini, electron capture (ECD) or electron transfer dissociation (ETD)
fragmentation methods sometimes lack good coverage of certain regions of the
protein, most often in the middle of the sequence. Ultraviolet photodissociation
(UVPD) is a recently developed fast-fragmentation technique, which provides
extensive backbone fragmentation that can be complementary in sequence coverage
to the aforementioned electron-based fragmentation techniques. Here, we explore
the application of electrospray ionization (ESI)-UVPD FTMS on an Orbitrap Fusion
Lumos Tribrid mass spectrometer to top-down HDX analysis of proteins. We have
incorporated UVPD-specific fragment-ion types and fragment-ion mixtures into our
isotopic envelope fitting software (HDX Match) for the top-down HDX analysis. We
have shown that UVPD data is complementary to ETD, thus improving the overall
resolution when used as a combined approach.
PMID- 29336550
TI - Phasor-Fluorescence Lifetime Imaging Microscopy Analysis to Monitor Intercellular
Drug Release from a pH-Sensitive Polymeric Nanocarrier.
AB - The design of highly efficient drug carriers, and the development of appropriate
techniques to monitor their mechanism of action and therapeutic effect, are both
critical for improving chemotherapy. Herein, a polymeric nanoparticle, PAH
Cit/DOX (poly(allylamine)-citraconic anhydride/doxorubicin), was synthesized and
used as a nanodrug system for the efficient delivery and pH-responsive release of
doxorubicin (DOX) into cancer cells. The PAH-Cit/DOX nanoparticles were stable at
physiological pH but effectively released DOX under weakly acidic conditions. The
release efficiency was 90.6% after 60 h of dialysis in phosphate-buffered saline
at pH 5.5. Confocal images showed the rapid movement of the drug from the
cytoplasm to the nucleus, indicating the effective drug release MCF-7 cells.
Notably, the combination of fluorescence lifetime imaging microscopy (FLIM) and
phasor analysis (phasor-FLIM) provides an approach to monitor the dynamic change
of DOX fluorescence lifetime in intercellular environments. Phasor-differentiated
lifetime pixel intensity in FLIM images was quantified and used to evaluate the
DOX release from nanocarriers, making it possible to detect the dynamics of
intracellular release and transport of DOX.
PMID- 29336551
TI - First Gut Instincts Are Always Right: The Resolution Required for a Mass Defect
Analysis of Polymer Ions Can Be as Low as Oligomeric.
AB - Its recent adaptation to low-resolution mass spectra of polymers using fractional
base units raises the question of the minimal resolution needed for a Kendrick
mass defect (KMD) analysis. Intuiting an oligomeric resolution since the mass of
a repeat unit is the sole value to be known, it is challenged by the relative
failure of the KMD plots computed from an isotopically resolved matrix-assisted
laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrum to display
clear alignments in the high mass range. Another procedure based on the
remainders of Kendrick mass (RKMs) overcomes this pitfall with oligomers
perfectly aligned in a new RKM plot. Despite a concomitant degradation of the
resolving power and accuracy, with the example of MALDI-TOF/TOF mass spectra of a
variety of homo- and copolymer ions, the RKM procedure still allows a rapid
enumeration, assignment, and any further manipulation of all the product ion
series in visual RKM plots. Successfully extended to the critical case of a MALDI
mass spectrum recorded with a linear TOF analyzer allowing a bare oligomeric
resolution, the RKM plot turns the distributions differing by their end-groups or
adducted ion into clear horizontal lines. It eventually gives intuition its due
by answering the original question: the minimal resolution required for a mass
defect analysis can be as low as oligomeric with the appropriate formulas.
PMID- 29336552
TI - Engineering the Surface of Therapeutic "Living" Cells.
AB - Biological cells are complex living machines that have garnered significant
attention for their potential to serve as a new generation of therapeutic and
delivery agents. Because of their secretion, differentiation, and homing
activities, therapeutic cells have tremendous potential to treat or even cure
various diseases and injuries that have defied conventional therapeutic
strategies. Therapeutic cells can be systemically or locally transplanted. In
addition, with their ability to express receptors that bind specific tissue
markers, cells are being studied as nano- or microsized drug carriers capable of
targeted transport. Depending on the therapeutic targets, these cells may be
clustered to promote intercellular adhesion. Despite some impressive results with
preclinical studies, there remain several obstacles to their broader development,
such as a limited ability to control their transport, engraftment, secretion and
to track them in vivo. Additionally, creating a particular spatial organization
of therapeutic cells remains difficult. Efforts have recently emerged to resolve
these challenges by engineering cell surfaces with a myriad of bioactive
molecules, nanoparticles, and microparticles that, in turn, improve the
therapeutic efficacy of cells. This review article assesses the various
technologies developed to engineer the cell surfaces. The review ends with future
considerations that should be taken into account to further advance the quality
of cell surface engineering.
PMID- 29336553
TI - Catalytic Mechanism of Cruzain from Trypanosoma cruzi As Determined from Solvent
Kinetic Isotope Effects of Steady-State and Pre-Steady-State Kinetics.
AB - Cruzain, an important drug target for Chagas disease, is a member of clan CA of
the cysteine proteases. Understanding the catalytic mechanism of cruzain is vital
to the design of new inhibitors. To this end, we have determined pH-rate profiles
for substrates and affinity agents and solvent kinetic isotope effects in pre
steady-state and steady-state modes using three substrates: Cbz-Phe-Arg-AMC, Cbz
Arg-Arg-AMC, and Cbz-Arg-Ala-AMC. The pH-rate profile of kcat/ Km for Cbz-Arg-Arg
AMC indicated p K1 = 6.6 (unprotonated) and p K2 ~ 9.6 (protonated) groups were
required for catalysis. The temperature dependence of the p K = 6.2-6.6 group
exhibited a Delta Hion value of 8.4 kcal/mol, typical of histidine. The pH-rate
profile of inactivation by iodoacetamide confirmed that the catalytic cysteine
possesses a p Ka of 9.8. Normal solvent kinetic isotope effects were observed for
both D2O kcat (1.6-2.1) and D2O kcat/ Km (1.1-1.4) for all three substrates. Pre
steady-state kinetics revealed exponential bursts of AMC production for Cbz-Phe
Arg-AMC and Cbz-Arg-Arg-AMC, but not for Cbz-Arg-Ala-AMC. The overall solvent
isotope effect on kcat can be attributed to the solvent isotope effect on the
deacylation step. Our results suggest that cruzain is unique among papain-like
cysteine proteases in that the catalytic cysteine and histidine have neutral
charges in the free enzyme. The generation of the active thiolate of the
catalytic cysteine is likely preceded (and possibly triggered) by a ligand
induced conformational change, which could bring the catalytic dyad into the
proximity to effect proton transfer.
PMID- 29336554
TI - Competition between Dehydrogenative Organometallic Bonding and Covalent Coupling
of an Unfunctionalized Porphyrin on Cu(111).
AB - We studied the formation of linked porphyrin oligomers from 5,15
diphenylporphyrin (2H-DPP) by thermal, substrate-assisted organometallic and
dehydrogenation coupling on Cu(111) by scanning tunneling microscopy. In the
range of 300-620 K, we find three distinct stages, at 300 K, the intact 2H-DPP
molecules self-assemble into linear structures held together by van der Waals
forces. Increasing the substrate temperature, self-metalation and intramolecular
ring-closing reactions result in planar and isolated DPP species on the surface.
By C-H cleavage, porphyrin oligomers bonded by organometallic and covalent bonds
between the modified DPP are formed. The amount of covalently bonded DPP
oligomers increases strongly with annealing time and temperature, and they become
the dominant species at 570 K. In contrast, the number of organometallically
bonded DPP oligomers increases moderately even up to 620 K, indicating that in
this case the organometallic bond is no precursor of the covalent bond.
PMID- 29336555
TI - Correction to Ozone Formation Induced by the Impact of Reactive Bromine and
Iodine Species on Photochemistry in a Polluted Marine Environment.
PMID- 29336556
TI - Linking Spectral Induced Polarization (SIP) and Subsurface Microbial Processes:
Results from Sand Column Incubation Experiments.
AB - Geophysical techniques, such as spectral induced polarization (SIP), offer
potentially powerful approaches for in situ monitoring of subsurface
biogeochemistry. The successful implementation of these techniques as monitoring
tools for reactive transport phenomena, however, requires the deconvolution of
multiple contributions to measured signals. Here, we present SIP spectra and
complementary biogeochemical data obtained in saturated columns packed with
alternating layers of ferrihydrite-coated and pure quartz sand, and inoculated
with Shewanella oneidensis supplemented with lactate and nitrate. A biomass
explicit diffusion-reaction model is fitted to the experimental biogeochemical
data. Overall, the results highlight that (1) the temporal response of the
measured imaginary conductivity peaks parallels the microbial growth and decay
dynamics in the columns, and (2) SIP is sensitive to changes in microbial
abundance and cell surface charging properties, even at relatively low cell
densities (<108 cells mL-1). Relaxation times (tau) derived using the Cole-Cole
model vary with the dominant electron accepting process, nitrate or ferric iron
reduction. The observed range of tau values, 0.012-0.107 s, yields effective
polarization diameters in the range 1-3 MUm, that is, 2 orders of magnitude
smaller than the smallest quartz grains in the columns, suggesting that
polarization of the bacterial cells controls the observed chargeability and
relaxation dynamics in the experiments.
PMID- 29336557
TI - Nitrosoallene-Mediated endo-Cyclizations for the Synthesis of (Hetero)cyclic
alpha-Substituted exo-Unsaturated Oximes.
AB - Nitrosoallene-mediated endo-dig cyclization reactions producing (hetero)cyclic
exo-unsaturated oximes (enoximes) are described. The intramolecular 1,4-type
addition to in situ generated nitrosoallenes afforded alpha-substituted cyclic
enoximes with exo-methylene units, which are the favored conformation for further
cyclizations. The strong electron-withdrawing ability of the nitroso group
facilitated the construction of five-to-seven-membered ring systems via C-O, C-N,
C-S, and C-C bond formations, including a quaternary carbon center, at low
temperatures.
PMID- 29336558
TI - Excited-State Processes of Cyclometalated Platinum(II) Charge-Transfer Dimers
Bridged by Hydroxypyridines.
AB - A series of four anti-disposed dinuclear platinum(II) complexes featuring metal
metal-to-ligand charge-transfer (MMLCT) excited states, bridged by either 2
hydroxy-6-methylpyridine or 2-hydroxy-6-phenylpyridine and cyclometalated with
7,8-benzoquinoline or 2-phenylpyridine, are presented. The 2-hydroxypyridine
bridging ligands control intramolecular d8-d8 metal-metal sigma interactions,
affecting the frontier orbitals' electronic structure, resulting in marked
changes to the ground- and excited-state properties of these complexes. Three of
these molecules possess reversible one-electron oxidations in cyclic voltammetry
experiments as a result of strong intramolecular metallophilic interactions. In
this series of molecules, X-ray crystallography revealed Pt-Pt distances ranging
between 2.815 and 2.878 A; the former represents the shortest reported metal
metal distance for platinum(II) dimers possessing low-energy MMLCT transitions.
All four molecules reported here display visible absorption bands beyond 500 nm
and feature MMLCT-based red photoluminescence (PL) above 700 nm at room
temperature with high PL quantum yields (up to 4%) and long excited-state
lifetimes (up to 341 ns). The latter were recorded using both transient PL and
transient absorption experiments that self-consistently yielded quantitatively
identical excited-state lifetimes. The energy-gap law was successfully applied to
this series of chromophores, documenting this behavior for the first time in
molecules possessing MMLCT excited states. The combined data illustrate that
entirely new classes of MMLCT chromophores can be envisioned using bridging
pyridyl hydroxides in cooperation with various C^N cyclometalates to achieve
photophysical properties suitable for excited-state electron- and energy-transfer
chemistry.
PMID- 29336559
TI - Investigation on Two Forms of Temperature-Sensing Parameters for Fluorescence
Intensity Ratio Thermometry Based on Thermal Coupled Theory.
AB - Absolute temperature sensitivity (Sa) reflects the precision of sensors that
belong to the same mechanism, whereas relative temperature sensitivity (Sr) is
used to compare sensors from different mechanisms. For the fluorescence intensity
ratio (FIR) thermometry based on two thermally coupled energy levels of one rare
earth (RE) ion, we define a new ratio as the temperature-sensing parameter that
can vary greatly with temperature in some circumstances, which can obtain higher
Sa without changing Sr. Further discussion is made on the conditions under which
these two forms of temperature-sensing parameters can be used to achieve higher
Sa for biomedical temperature sensing. Based on the new ratio as the temperature
sensing parameter, the Sa and Sr of the BaTiO3: 0.01%Pr3+, 8%Yb3+ nanoparticles
at 313 K reach as high as 0.1380 K-1 and 1.23% K-1, respectively. Similarly, the
Sa and Sr of the BaTiO3: 1%Er3+, 3%Yb3+ nanoparticles at 313 K are as high as
0.0413 K-1 and 1.05% K-1, respectively. By flexibly choosing the two ratios as
the temperature-sensing parameter, higher Sa can be obtained at the target
temperature, which means higher precision for the FIR thermometers.
PMID- 29336560
TI - Trifluoromethyl-Substituted Iridium(III) Complexes: From Photophysics to
Photooxidation of a Biological Target.
AB - Photodynamic therapeutic agents are of key interest in developing new strategies
to develop more specific and efficient anticancer treatments. In comparison to
classical chemotherapeutic agents, the activity of photodynamic therapeutic
compounds can be finely controlled thanks to the light triggering of their
photoreactivity. The development of type I photosensitizing agents, which do not
rely on the production of ROS, is highly desirable. In this context, we developed
new iridium(III) complexes which are able to photoreact with biomolecules;
namely, our Ir(III) complexes can oxidize guanine residues under visible light
irradiation. We report the synthesis and extensive photophysical characterization
of four new Ir(III) complexes, [Ir(ppyCF3)2(N^N)]+ [ppyCF3 = 2-(3,5
bis(trifluoromethyl)phenyl)pyridine) and N^N = 2,2'-dipyridyl (bpy); 2-(pyridin-2
yl)pyrazine (pzpy); 2,2'-bipyrazine (bpz); 1,4,5,8-tetraazaphenanthrene (TAP)].
In addition to an extensive experimental and theoretical study of the
photophysics of these complexes, we characterize their photoreactivity toward
model redox-active targets and the relevant biological target, the guanine base.
We demonstrate that photoinduced electron transfer takes place between the
excited Ir(III) complex and guanine which leads to the formation of stable
photoproducts, indicating that the targeted guanine is irreversibly damaged.
These results pave the way to the elaboration of new type I photosensitizers for
targeting cancerous cells.
PMID- 29336561
TI - A Borane Platinum Complex Undergoing Reversible Hydride Migration in Solution.
AB - Reaction of [Pt(kappa2-C,N-ppy)(dmso)Cl], 1 (Hppy = 2-phenylpyridine), with
Na[H2B(mb)2] (Hmb = 2-mercapto-benzimidazole) smoothly afforded the complex
{[(kappa3-S,B,S-HB(mb)2]Pt(kappa2-C,N-ppy)H}, 2, featuring a strong reverse
dative Pt -> B sigma interaction in the solid state. When dissolved in thf (or
acetone) solution, 2 undergoes a reversible Pt-H bond activation, establishing an
equilibrium between the hexacoordinated 2 and the tetracoordinate complex
{[(kappa2-S,S-H2B(mb)2]Pt(kappa2-C,N-ppy)}, 3, as ascertained by multinuclear
NMR. Hydrolysis of the B-N bond in 2/3 resulted ultimately in the formation of a
dimeric half-lantern platinum(II,II) complex [{Pt(kappa2-C,N-ppy)(MU2-kappa2-N,S
mb)}2], 4. The SC-XRD structures of 2 and 4 are reported.
PMID- 29336562
TI - Neutron Diffraction Study on the Structure of Hydrated Li+ in Dilute Aqueous
Solutions.
AB - Neutron diffraction measurements have been carried out for 6Li/7Li isotopically
substituted aqueous 1.0 mol % (0.5 mol/kg) LiCl and 1.1 mol % (0.56 mol/kg)
LiClO4 solutions in D2O to obtain structural insight concerning hydration
structure of Li+ in more dilute electrolyte solutions. The first-order difference
function, DeltaLi(Q), was analyzed by means of the least squares fitting
procedure to obtain short-range structural parameters around the Li+. It was
revealed that the nearest neighbor Li+...O(D2O) distance, rLiO, and the
coordination number, nLiO, for the aqueous 1.0 mol % LiCl solution are 2.01 +/-
0.02 A and 5.9 +/- 0.1, respectively. The values, rLiO = 1.97 +/- 0.02 A and nLiO
= 6.1 +/- 0.1, are obtained for aqueous 1.1 mol % LiClO4 solution. These results
indicate that the hydration number of Li+ in a dilute solution is close to 6,
which is much larger than 4, which has long been believed. A possible explanation
is that the hydration number of Li+ varies with the solute concentration.
PMID- 29336563
TI - Electron Precise Group 5 Dimetallaheteroboranes [{CpV(MU-EPh)}2{MU-eta2:eta2
BH3E}] and [{CpNb(MU-EPh)}2{MU-eta2:eta2-B2H4E}] (E = S or Se).
AB - Synthesis and structural elucidation of various electron precise group 5
dimetallaheteroboranes have been described. Room temperature reaction of
[Cp2VCl2] with Li[BH3(EPh)], generated from the treatment of LiBH4.THF and Ph2E2
(E = S or Se), for 1 h in toluene, followed by thermolysis, led to the formation
of bimetallic complexes [{CpV(MU-EPh)}2{MU-eta2:eta2-BH3E}], 1 and 2 (1: E = S
and 2: E = Se), and [{CpV(MU-SePh)}2{MU-eta2:eta2-BH(OC4H8)Se}], 3. One of the
striking features of these compounds is that they represent a rare class of
distorted tetrahedral clusters having bridging hydrogens. Evaluating the skeletal
electron pairs and bonding types, compounds 1, 2, and 3 may be considered as
isoelectronic with our earlier reported [(CpV)2(B2H6)2]. In an attempt to
synthesize the Nb analogues of 1-3, room temperature reactions of [CpNbCl4] and
Li[BH3(EPh)] (E = S or Se) were carried out that afforded compounds [{CpNb(MU
EPh)}2{MU-eta2:eta2-B2H4E}], 4 and 5 (4: E = S and 5: E = Se). The solid-state X
ray structures of both 4 and 5 exemplify electronically saturated [M2B3] systems,
and their geometries are analogous to that of [(Cp*MoCl)2B3H7]. For the extension
of this work, reaction of [Cp*TaCl4] (Cp* = eta5-C5Me5) with Li[BH3(SePh)] was
carried out that yielded a tantalaselenaborane cluster [(Cp*Ta)2(MU
Se)B3H6Se(C6H5)] (6). All the new compounds have been characterized using 1H,
11B{1H}, 13C{1H} NMR, UV-vis absorption, and IR spectroscopy, mass spectrometry,
and X-ray diffraction studies.
PMID- 29336564
TI - Benzophenone-4 Promotes the Growth of a Pseudomonas sp. and Biogenic Oxidation of
Mn(II).
AB - Interactions between microbes and micropollutants (MPs) play a crucial role in
water purification or treatment. Current studies have generally focused on the
direct degradation or cometabolism of MPs. Considering the increasing interest in
and importance of the roles of MPs in microbial metabolism, we adopted an Mn(II)
oxidizing Pseudomonas sp. QJX-1 using tyrosine (Tyr) as the sole carbon and
nitrogen source to investigate the effects of seven MPs on its growth and
function. Six MPs exhibited an inhibition effect on bacterial growth and Mn(II)
oxidation. Only benzophenone-4 (BP-4) promoted the growth of QJX-1 and biogenic
oxidation Mn(II), but its concentration was not directly coupled to growth, which
was unexpected. RNA-seq data suggested that the addition of BP-4 did not
significantly change the basic metabolic function of QJX-1, but stimulated the
upregulation of the pyruvate and gluconeogenesis metabolic pathways of Tyr for
QJX-1 growth. Furthermore, protein identification and extracellular superoxide
detection indicated that Mn(II) oxidation was largely driven by the formation of
superoxide in response to Tyr starvation; the acceleration of superoxide
production, due to BP-4 accelerating Tyr consumption, was responsible for the
promotion effect of BP-4 on QJX-1 Mn(II) oxidation. Our findings highlight the
dual effects that MPs can have on the growth and function of a single strain in
aquatic ecosystem, i.e., the coexistence of inhibition and promotion.
PMID- 29336565
TI - Appearances of Fukushima Daiichi Nuclear Power Plant-Derived 137Cs in Coastal
Waters around Japan: Results from Marine Monitoring off Nuclear Power Plants and
Facilities, 1983-2016.
AB - Monitoring of 137Cs in seawater in coastal areas around Japan between 1983 and
2016 yielded new insights into the sources and transport of Fukushima Daiichi
Nuclear Power Plant (FDNPP)-derived 137Cs, particularly along the west coast of
Japan. Before the FDNPP accident (1983-2010), the activity concentrations of
137Cs, mainly from fallout, were decreasing exponentially. Effective 137Cs half
lives in surface seawater ranged from 15.6 to 18.4 yr. After the FDNPP accident
(March 2011) 137Cs activity concentrations in seawater off Fukushima and
neighboring prefectures immediately increased. Since May/June 2011, 137Cs
activity concentrations there have been declining, and they are now approaching
preaccident levels. Along the west coast of Japan remote from FDNPP (i.e., the
Japan Sea), however, radiocesium activity concentrations started increasing by
2013, with earlier (May/June 2011) increases at some sites due to airborne
transport and fallout. The inventory of 137Cs in the Japan Sea (in the main body
of the Tsushima Warm Current) in 2016 was calculated to be 0.97 * 1014 Bq,
meaning that 0.44 * 1014 Bq of FDNPP-derived 137Cs was added to the estimated
global fallout 137Cs inventory in 2016 (0.53 * 1014 Bq). The net increase of
137Cs inventory in the Japan Sea through the addition of FDNPP-derived 137Cs
accounts for approximately 0.2% of the total 137Cs flux from the plant to the
ocean from the accident.
PMID- 29336566
TI - Electrochemistry of Bis(pyridine)cobalt (Nitrophenyl)corroles in Nonaqueous
Media.
AB - A series of bis(pyridine)cobalt corroles with one or three nitrophenyl groups on
the meso positions of the corrole macrocycle were synthesized and characterized
as to their electrochemical and spectroscopic properties in dichloromethane,
benzonitrile, and pyridine. The potentials for each electrode reaction were
measured by cyclic voltammetry and the electron-transfer mechanisms evaluated by
analysis of the electrochemical data combined with UV-visible spectra of the
neutral, electroreduced, and electroxidized forms of the corroles. The proposed
electronic configurations of the initial compounds and the prevailing redox
reactions involving the electroactive central cobalt ion, the electroactive
conjugated macrocycle, and the electroactive meso-nitrophenyl groups are all
discussed in terms of solvent binding and the number of the nitrophenyl groups
and other substituents on the meso-nitrophenyl rings of the compounds.
PMID- 29336567
TI - Nonisothermal Spreading Dynamics of Self-Rewetting Droplets.
AB - We experimentally studied the spreading dynamics of binary alcohol mixtures (and
pure liquids for reference) deposited on a heated substrate in a partially
wetting situation under nonisothermal conditions. We show that the spreading
mechanism of an evaporating droplet exhibits a power-law growth with early-stage
exponents that depend strongly and nonmonotonically on the substrate temperature.
Moreover, we investigated the temporal and spatial thermal dynamics in the
droplet using infrared thermography, revealing the existence of unique thermal
patterns due to thermal and/or solutal instabilities, which lead to surface
tension gradients, namely the Marangoni effect. Our key findings are that the
temperature of the substrate drastically affects the early-stage inertial
capillary spreading regime owing to the nonmonotonic surface tension-temperature
dependence of the self-rewetting liquids. At later stages of wetting, the
spreading dynamics enters the viscous-capillary dominated regime, with the
characteristic low kinetics mirroring the behavior of pure liquids.
PMID- 29336569
TI - Paper-Based DNA Reader for Visualized Quantification of Soil-Transmitted Helminth
Infections.
AB - Soil-transmitted helminth (STH) infections are a global health issue affecting
nearly one-third of the world's population. As most endemic areas of STH are
impoverished countries or regions with limited healthcare resources, the accurate
diagnosis of STH requires analytical tools that are not only quantitative, but
also portable, inexpensive, and with no or minimal demand for external
instrument. Herein, we introduce a novel paper-based diagnostic device, termed
quantitative paper-based DNA reader (qPDR), capable of quantifying STH at the
molecular level by measuring distance as readout, thus eliminating the need for
external readers. On the basis of the unique interfacial interaction of a DNA
intercalating dye, SYBR Green I, with native cellulose on a chromatographic
paper, qPDR allows the distance-based quantification of minute amounts of double
stranded DNA as short as 6 min. By integrating qPDR with polymerase chain
reactions that were performed using a smartphone-controlled portable thermal
cycler, we were able to quantify minute amount of genetic markers from adult
worms of an STH (Trichuris trichiura) that were expelled post-treatment by
infected children living in the rural areas of Honduras.
PMID- 29336568
TI - Strain Distribution Across an Individual Shear Band in Real and Simulated
Metallic Glasses.
AB - Because of the fast dynamics of shear band formation and propagation along with
the small size and transient character of the shear transformation zones (STZs),
the elementary units of plasticity in metallic glasses, the description of the
nanoscale mechanism of shear banding often relies on molecular dynamics (MD)
simulations. However, the unrealistic parameters used in the simulations related
to time constraints may raise questions about whether quantitative comparison
between results from experimental and computational analyses is possible. Here,
we have experimentally analyzed the strain field arising across an individual
shear band by nanobeam X-ray diffraction and compared the results with the strain
characterizing a shear band generated by MD simulations. Despite their largely
different spatiotemporal scales, the characteristic features of real and
simulated shear bands are strikingly similar: the magnitude of the strain across
the shear band is discontinuous in both cases and the direction of the principal
strain axes exhibits the same antisymmetric profile. This behavior can be
explained by considering the mechanism of STZ activation and percolation at the
nanoscale, indicating that the nanoscale effects of shear banding are not limited
to the area within the band but they extend well into the surrounding elastic
matrix. These findings not only demonstrate the reliability of MD simulations for
explaining (also quantitatively) experimental observations of shear banding but
also suggest that designed experiments can be used the other way around to verify
numerical predictions of the atomic rearrangements occurring within a band.
PMID- 29336570
TI - Design of Near-Infrared Luminescent Lanthanide Complexes Sensitive to
Environmental Stimulus through Rationally Tuning the Secondary Coordination
Sphere.
AB - The design of near-infrared (NIR) emissive lanthanide (Ln) complexes sensitive to
external stimulus is fundamentally important for the practical application of Ln
materials. Because NIR emission from Ln is extremely sensitive to X-H (X = C, N
and O) bond vibration, we herein report to harness the secondary coordination
sphere to design NIR luminescent lanthanide sensors. Toward this goal, we
designed and synthesized two isomeric [(eta5-C5H5)Co{(D3CO)2P = O}3]-Yb(III)
7,8,12,13,17,18-hexafluoro-5,10,15,20-tetrakis(pentafluorophenyl)porpholactol NIR
emitters, Yb-up and Yb-down, based on the stereoisomerism of porphyrin peripheral
beta-hydroxyl group. Yb-up, in which beta-OH is at the same side of Yb(III)
center, can form an intramolecular hydrogen bond with the axial Klaui ligand,
whereas Yb-down cannot because its beta-OH is opposite to Yb(III) center. X-ray
crystal structures and photophysical studies suggested that the intramolecular
hydrogen bond plays important roles on the NIR luminescence of ytterbium(III),
which shortens the distance between beta-OH and Yb(III) and facilitates the
nonradiative deactivation of Ln excited state. Importantly, Yb-up/down were
demonstrated to be highly sensitive toward temperature and viscosity. The PMMA
polymer using Yb-up as the dopant NIR emitter showed thermosensitivity up to 6.0%
degrees C-1 in the wide temperature range of 77-400 K, higher than that of Yb
down (3.8% degrees C-1). These complexes were also explored as the first NIR
viscosity sensor, revealing their potential applications as optical sensors
without visible light interference. This work demonstrates the importance of
secondary coordination sphere on designing NIR Ln luminescent functional
materials.
PMID- 29336571
TI - Atmospheric Processing and Iron Mobilization of Ilmenite: Iron-Containing Ternary
Oxide in Mineral Dust Aerosol.
AB - Over the last several decades, iron has been identified as a limiting nutrient in
about half of the world's oceans. Its most significant source is identified as
deposited iron-containing mineral dust that has been processed during atmospheric
transportation. The current work focuses on chemical and photochemical processing
of iron-containing mineral dust particles in the presence of nitric acid, and an
organic pollutant dimethyl sulfide under atmospherically relevant conditions.
More importantly, ilmenite (FeTiO3) is evaluated as a proxy for the iron
containing mineral dust. The presence of titanium in its lattice structure
provides higher complexity to mimic mineral dust, yet it is simple enough to
study reaction pathways and mechanisms. Here, spectroscopic methods are combined
with dissolution measurements to investigate atmospheric processing of iron in
mineral dust, with specific focus on particle mineralogy, particle size, and
their environmental conditions (i.e., pH and solar flux). Our results indicate
that the presence of titanium elemental composition enhances iron dissolution
from mineral dust, at least by 2-fold comparison with its nontitanium-containing
counterparts. The extent of iron dissolution and speciation is further influenced
by the above factors. Thus, our work highlights these important, yet
unconsidered, factors in the atmospheric processing of iron-containing mineral
dust aerosol.
PMID- 29336572
TI - {[Hg(SCN)3]2(MU-L)}2-: An Efficient Secondary Building Unit for the Synthesis of
2D Iron(II) Spin-Crossover Coordination Polymers.
AB - We report an unprecedented series of two-dimensional (2D) spin-crossover (SCO)
heterobimetallic coordination polymers generically formulated as
{FeII[(HgII(SCN)3)2](L)x}.Solv, where x = 2 for L = tvp (trans-(4,4'
vinylenedipyridine)) (1tvp), bpmh ((1E,2E)-1,2-bis(pyridin-4
ylmethylene)hydrazine) (1bpmh.nCH3OH; n = 0, 1), bpeh ((1E,2E)-1,2-bis(1-(pyridin
4-yl)ethylidene)hydrazine) (1bpeh.nH2O; n = 0, 1) and x = 2.33 for L = bpbz (1,4
bis(pyridin-4-yl)benzene) (1bpbz.nH2O; n = 0, 2/3). The results confirm that self
assembly of FeII, [HgII(SCN)4]2-, and ditopic rodlike bridging ligands L
containing 4-pyridyl moieties favors the formation of linear [Fe(MU-L)]n2n+
chains and in situ generated binuclear units {[HgII(SCN)3]2(MU-L)}2-. The latter
act as bridges between adjacent chains generating robust 2D layers. The [FeIIN6]
centers are equatorially surrounded by four NCS- groups and two axial N atoms of
the organic ligand L. The compound 1tvp and the unsolvated form of 1bpmh undergo
complete SCO centered at T1/2 = 177 and 226 K, characterized by the enthalpy and
entropy variations DeltaH = 12.3 and 10.5 kJ mol-1 and DeltaS = 69.4 and 48 J K-1
mol-1, respectively. The almost complete SCO of the unsolvated form of 1bpeh
occurs at ca. T1/2 = 119 K and exhibits a complete LIESST effect. Regardless of
the degree of solvation, a half-spin conversion at T1/2 < 100 K occurs for
1bpbz.nH2O, which becomes almost complete at p = 0.65 GPa. The labile solvent
molecules present in 1bpmh.CH3OH and 1bpeh.H2O have a dramatic influence on the
corresponding SCO behavior.
PMID- 29336573
TI - Biomimetic Enantioselective Total Synthesis of (-)-Petromindole.
AB - The first enantioselective total synthesis of (-)-petromindole, an
architecturally distinct congener of indole diterpene family, has been achieved.
Key features of this synthetic route include the scalable and concise synthesis
of tricyclic allylic alcohol from enantiopure Wieland-Mischer ketone derivative,
and TMSOTf-mediated, highly efficient biomimetic C-4 cyclization of indole
derivative for the rapid construction of a hexacyclic skeleton of petromindole.
PMID- 29336574
TI - Janus-Type Gold/Polythiophene Composites Formed via Redox Reaction at the Ionic
Liquid|Water Interface.
AB - Janus-type Au/polythiophene (PT) composites have been prepared by utilizing the
liquid/liquid interface between water (W) and a hydrophobic ionic liquid (IL) as
the redox reaction site. AuCl4- is reductively deposited, and terthiophene is
oxidatively polymerized spacio-selectively at the IL|W interface, leading to the
formation of the Au/PT composites. The composites are Janus-type Au-attached PT
plates with two surface morphologies, flat surface and flowerlike surface at the
W and IL sides of the plates at the IL|W interface, respectively. Not only
surface morphologies but also attached Au structures are different at the two
surfaces; Au microurchins on the flat surface and dendritic Au nanofibers on the
flowerlike surface. Optical and scanning electron microscopic observations have
revealed that nanofibers and microurchins are formed at the early and later stage
of the reaction, respectively. Electrochemistry at the IL|W interface has
illustrated that electron transfer across the IL|W interface during the formation
of the Janus-type Au/PT composites is coupled with ion transfer of AuCl4- to
compensate for the charge unbalance in the two liquid phases. AuCl4- transferred
into IL is found to be the source of the dendritic Au nanofibers formed at the IL
side of the PT plates.
PMID- 29336576
TI - Dicyclopentyl Dithiosquarate as an Intermediate for the Synthesis of
Thiosquaramides.
AB - A general and greatly improved route is reported for the synthesis of a variety
of thiosquaramides from a common dithionated intermediate. Both diaryl
thiosquaramides and bifunctional thiosquaramides are readily accessed from
dicyclopentyl dithiosquarate via two addition-elimination reactions. The
convenient handling characteristics and relative stability of associated
intermediates enable an operationally simple thiosquaramide preparation.
Bifunctional aryl thiosquaramides, which were inaccessible by the previous
method, are also prepared, and their catalytic performance is demonstrated,
including their capability to function as Bronsted acid catalysts.
PMID- 29336577
TI - [Indications to liver transplantation].
AB - Liver transplantation should be considered in patients with end-stage liver
disease in whom this operation would extend life expectancy beyond what the
natural history of underlying disease would predict or in whom transplantation is
likely to substantially improve the quality of life. Liver transplantation is
indicated in end-stage liver disease, in selected liver tumors and in fulminant
liver failure. The most common indication in adult to transplantation is
decompensated liver cirrhosis with life expectancy one year or less. Evaluation
and referral to transplantation center should be considered when a major
complication of liver cirrhosis occurs - ascites, bleeding due to portal
hypertension, hepatorenal syndrome or hepatic encephalopathy. MELD score 15 is
recommended to list patients with end-stage liver disease. In recent years the
indication of decompensated cirrhosis B and C is declining, on contrary, there is
an increase in indication for hepatocellular carcinoma and NASH. An extension of
indications has been observed recently - patients above 70 years of age, patients
with neuroendocrine tumors among others. In 2016 in Czech Republic total 179
livers were transplanted, but only a small fraction of potential candidates was
referred to transplant centers.
PMID- 29336575
TI - Challenges in the Conversion of Manual Processes to Machine-Assisted Syntheses:
Activation of Thioglycoside Donors with Aryl(trifluoroethyl)iodonium Triflimide.
AB - The steps needed to adapt a stable iodonium promoter for use in automated
fluorous-assisted solution-phase oligosaccharide synthesis are described. Direct
adaptation of the originally reported batch procedure resulted in the formation
of an orthoester or protecting group transfer to the glycosyl acceptor.
Fortunately, the addition of inexpensive beta-pinene as an acid scavenger avoided
both of these side reactions. The utility of this newly developed protocol was
applied to the automated solution-phase synthesis of a beta-glucan fragment.
PMID- 29336578
TI - [Intestinal transplantation in Czech Republic].
AB - : Intestinal transplantation represents a suitable treatment for patients with
intestinal failure who then develop life-threatening complications of total
parenteral nutrition and for some patients with complex abdominal disorders not
suitable for conventional treatment. METHODS: prior to launch of the clinical
program, preparation started in 2006 initially with extensive experimentation
carried out on pigs. The clinical phase involved a specialized, multidisciplinary
team who examined 23 patients being considered for transplantation. Seven
patients were put on a waiting list and one female, due to the improvement of her
medical status, was unlisted. The first ever intestinal transplantation was done
in 2014. RESULTS: three out of six transplanted patients are alive with 380 days
of actual survival; median 131 days (63-763). Two patients are on a full oral
diet and nutritionally independent with an excellent quality of life. One female
is nutritionally independent but with the need for partial supplemental
parenteral rehydration due to the stomal output. CONCLUSION: intestinal
transplantation is a suitable treatment for highly selected patients with
intestinal failure who meet specific listing criteria.
PMID- 29336579
TI - [Pros and cons of dual kidney transplantation].
AB - Dual kidney transplantation is one of the options to utilize so called marginal
grafts, kidneys that would be insufficient for normal single transplantation.
This time consuming and burdensome surgical procedure can be beneficial in
precisely selected patients. This method requires correct algorithm of donors and
recipients selections, than we can expect the best results.Key words: dual kidney
transplantation, marginal donor, chronic renal failure, expanded criteria donor.
PMID- 29336580
TI - Organ transplantation from donors after circulatory death.
AB - The scarcity of organs for transplantation resulted in the increase of organ
donation after circulatory death. This review describes the current practice with
donors after circulatory death (DCD), recent classification of DCD and organ
procurement from DCD. Then the outcome of organ transplantation from is discussed
and the new strategies in DCD are presented. Despite of the fact that DCD are
extended criteria donors, strict organ selection and novel technologies as
machine perfusion or normothermic perfusion allows better utilization of DCD with
a similar outcome as from donors after brain death.
PMID- 29336581
TI - [Organ transplantation from donors after circulatory death].
AB - The scarcity of organs for transplantation resulted in the increase of organ
donation after circulatory death. This review describes the current practice with
donors after circulatory death (DCD), recent classification of DCD and organ
procurement from DCD. Then the outcome of organ transplantation from is discussed
and the new strategies in DCD are presented. Despite of the fact that DCD are
extended criteria donors, strict organ selection and novel technologies as
machine perfusion or normothermic perfusion allows better utilization of DCD with
a similar outcome as from donors after brain death.
PMID- 29336582
TI - [Psychological evaluation of uterus transplantation trial participants].
AB - Uterus transplantation is a life-giving and quality-of-life enhancing
transplantation. Life with transplanted uterus is a transitional phase of life
for both recipients and their partners. Six deliveries of healthy children from
five transplanted mothers out of 9 uterus transplantations in Sweden may
encourage untimely hopes of thousands of women with absolute uterine factor
infertility worldwide. Psychological evaluation might be included into all trials
regarding new treatment methods and treatment procedures. Main psychological
issues connected with the infertility treatment in women with absent uterus are
clearly defined (especially in vitro fertilization, uterus transplantation,
compliance with immunosuppressive treatment, ultrasound examinations of uterine
vascular perfusion, rejection signs surveillance, embryo transfer, pregnancy,
cesarean section, preterm delivery risk, puerperium, hysterectomy and
immunosuppressive treatment termination). The role of psychological evaluation of
participants before the admission to complicated treatment process is to choose
those who will be able to cope all mentioned difficulties and unexpected
complications including potential failure of the whole treatment without serious
negative impact on their psychological situation. Up to now experience with
psychological stability of our 7 uterus recipients and 3 uterus living donors are
good although post-transplant period is especially in recipients connected with
everyday psychological adaptation on the significant life changes. We are aware
that psychological evaluation of our study participants will require further 3
years of follow up with publication of our results.
PMID- 29336583
TI - [Psychological problems of patients who survived cardiac arrest out of hospital].
AB - Out-of-hospital circulatory arrest is a major challenge of current medicine.
Circulatory arrest survivors bear increased risk of developing anxiety disorders
and depressions both during hospitalization and after discharging to the home
care. Circulatory arrest survivors are not provided routinely with psychological
care. Patients included in our pilot research were identified in the register of
surviving circulatory arrest. The survey was carried out using a non-standardized
questionnaire. A total of 28 patients surviving the circulatory arrest were
included in the pilot research. The average age of respondents was 54 years.
There were 20 men and 8 women. The project showed that 18 (64.3 %) people, since
they went through the critical status, have suffered from negative and bothering
symptoms, such as: fear of a repeated cardiac arrest, sleeping disorders,
persistent tiredness etc. Despite the fact that our group of patients was
relatively small and larger studies addressing the issue are needed, our finding
is alarming - the patients after the cardiac arrest suffer from many anxious and
depressive symptoms as well as from cognitive deficit. In the situation when the
common psychological intervention by a specialist is not provided, it seems that
an early psychological invention is highly desirable and may have a beneficial
effect on return of the patients to their everyday life.
PMID- 29336584
TI - [Current macro-diagnostic trends of forensic medicine in the Czech Republic].
AB - Over the last few years, advanced diagnostic methods have penetrated in the realm
of forensic medicine in addition to standard autopsy techniques supported by
traditional X-ray examination and macro-diagnostic laboratory tests. Despite the
progress of imaging methods, the conventional autopsy has remained basic and
essential diagnostic tool in forensic medicine. Postmortem computed tomography
and magnetic resonance imaging are far the most progressive modern radio
diagnostic methods setting the current trend of virtual autopsies all over the
world. Up to now, only two institutes of forensic medicine have available
postmortem computed tomography for routine diagnostic purposes in the Czech
Republic. Postmortem magnetic resonance is currently unattainable for routine
diagnostic use and was employed only for experimental purposes. Photogrammetry is
digital method focused primarily on body surface imaging. Recently, the most
fruitful results have been yielded from the interdisciplinary cooperation between
forensic medicine and forensic anthropology with the implementation of body
scanning techniques and 3D printing. Non-invasive and mini-invasive investigative
methods such as postmortem sonography and postmortem endoscopy was
unsystematically tested for diagnostic performance with good outcomes despite of
limitations of these methods in postmortem application. Other futuristic methods,
such as the use of a drone to inspect the crime scene are still experimental
tools. The authors of the article present a basic overview of the both routinely
and experimentally used investigative methods and current macro-diagnostic trends
of the forensic medicine in the Czech Republic.
PMID- 29336585
TI - [The Guideline on Spiritual Care of the Ministry of Health of the Czech
Republic].
AB - In April 2017, the Ministry of Health of the Czech Republic issued a Guideline on
Spiritual Care in Bedside Medical Facilities of Medical Service Providers.
Through this document, the ministry established the much-needed framework for the
operation of hospital chaplains in medical facilities, including the conditions
for their activities, and defined some terms such as spiritual care, chaplains,
etc. Although this is an important initiative on the part of the ministry, the
guideline does not cover a number of aspects of spiritual care in bedside medical
facilities and will need some specification and completion.
PMID- 29336586
TI - Image Information Obtained Using a Charge-Coupled Device (CCD) Camera During an
Immersion Liquid Evaporation Process for Measuring the Refractive Index of Solid
Particles.
AB - The refractive index is a fundamental physical property of a medium, which can be
used for the identification and purity issues of all media. Here we describe a
refractive index measurement technique to determine simultaneously the refractive
index of different solid particles by monitoring the transmittance of light from
a suspension using a charge-coupled device (CCD) camera. An important feature of
the measurement is the liquid evaporation process for the refractive index
matching of the solid particle and the immersion liquid; this was realized by
using a pair of volatile and non-volatile immersion liquids. In this study,
refractive indices of calcium fluoride (CaF2) and barium fluoride (BaF2) were
determined using the proposed method.
PMID- 29336587
TI - Spatially Resolved Spectral Powder Analysis: Experiments and Modeling.
AB - Understanding the behavior of light in granular media is necessary for
determining the sample size, shape, and weight when probing using fiber optic
setups. This is required for a correct estimate of the active pharmaceutical
ingredient content in a pharmaceutical blend via near-infrared spectroscopy.
Several strategies to describe the behavior of light in granular and turbid media
exist. A common approach is the Monte-Carlo simulation of individual photons and
their description using mean free path lengths for scattering and absorption. In
this work, we chose a complementary method by approximating these parameters via
real physical counterparts, i.e., the particle size, shape, and density and the
resulting chord lengths. Additionally, the wavelength dependence of refractive
indices is incorporated. The obtained results were compared with those obtained
in an experimental setup that included the SAM-Spec Felin probe head by Indatech
for detecting spatially resolved spectra of samples. Our method facilitates the
interpretation of the acquired experimental results by contrasting the optical
response, the physical particle attributes, and the simulation results.
PMID- 29336588
TI - Uncertainty of Integrated Intensity Following Line Profile Fitting of Multiline
Spectra.
AB - A novel method of determining the total uncertainty in the integrated intensity
of fitted emission lines in multipeaked emission spectra is presented. The
proposed method does not require an assumption of the type of line profile to be
specified. The absolute difference between a fit and measured spectrum defines
the uncertainty of the integrated signal intensity and is subsequently decomposed
to determine the uncertainty of each peak in multiline fits. Decomposition relies
on tabulating a weighting factor, which describes how each peak contributes to
the total integral uncertainty. Applications of this method to quantitative
approaches in laser-induced breakdown spectroscopy analysis are described.
PMID- 29336589
TI - Near-Infrared Spectroscopy Screening to Allow Detection of Pathogenic
Mitochondrial DNA Variants in Individuals with Unexplained Abnormal Fatigue: A
Preliminary Study.
AB - Unexplained abnormal fatigue is characterized by chronic fatigue persisting for
at least six months and not sufficiently explained by any recognized medical
condition. In this pilot study, twelve individuals with abnormal fatigue
remaining unexplained after thorough screening were investigated using a near
infrared (NIR) spectroscopy handgrip test. Four of them were found to have an
abnormal oxygen extraction pattern similar to participants with documented
mitochondrial myopathy. In three of the four individuals, diverse mitochondrial
abnormalities were documented by spectrophotometric, immunocytological,
fluorescent, and morphological analyses performed in skeletal muscle and in
cultured skin fibroblasts. Three of the four participants with decreased muscular
oxygen extraction were each shown to harbor a different homoplasmic pathogenic
mitochondrial DNA point mutation (m.961T > C, m.1555A > G, m.14484T > C). In the
fourth participant, the presence of multiple large mitochondrial DNA deletions
was suspected in muscle tissue. In contrast, none of the eight abnormally
fatigued participants with normal NIR spectroscopy results harbored either a
pathogenic mitochondrial DNA point mutation or large deletions ( P < 0.001). This
pilot study shows that NIR spectroscopy may serve as a noninvasive screening tool
to delineate a subgroup (of participants) with mitochondrial dysfunction among
the large group of individuals with unexplained abnormal fatigue.
PMID- 29336590
TI - Modern perspectives on the health benefits of kefir in next generation sequencing
era: Improvement of the host gut microbiota.
AB - Kefir is a natural complex fermented milk product containing more than 50 species
of probiotic bacteria and yeast, and has been demonstrated to have multiple
properties conferring health benefits, including antiobesity, anti-hepatic
steatosis, antioxidative, antiallergenic, antitumor, anti-inflammatory,
cholesterol-lowering, constipation-alleviating, and antimicrobial properties. To
better understand the underlying mechanisms of these benefits, we here review
research on the effect of kefir (and kefir microorganisms) consumption to
modulate the host gut microbiota. Owing to its excellent gastrointestinal
resistance and colonization ability and wide ranges of microbial interaction,
kefir has shown significant and wide-spectrum modulatory effects on the host gut
microbiota. In particular, as a bacteria- and yeast-containing food, kefir can
modulate both the gut microbiota and mycobiota. Since the association of this
modulation with health benefit has only been addressed in a small number of
recent studies thus far, further studies are needed to determine the precise
mechanisms of the beneficial effects of kefir in relation to the modulation of
the gut microbiota and mycobiota. Gaining this insight will surely help to take
full advantage of this unique probiotic food.
PMID- 29336591
TI - Adherence to antiretroviral therapy, stigma and behavioral risk factors in HIV
infected adolescents in Asia.
AB - We studied behavioral risks among HIV-infected and uninfected adolescents using
an audio computer-assisted self-interview. A prospective cohort study was
initiated between 2013 and 2014 in Malaysia, Thailand, and Vietnam. HIV-infected
adolescents were matched to uninfected adolescents (4:1) by sex and age group (12
14 and 15-18 years). We enrolled 250 HIV-infected (48% male; median age 14.5
years; 93% perinatally infected) and 59 uninfected (51% male; median age 14.1
years) adolescents. At enrollment, HIV-infected adolescents were on
antiretroviral therapy (ART) for a median (IQR) of 7.5 (4.7-10.2) years, and 14%
had HIV-RNA >1000 copies/mL; 19% reported adherence <80%. Eighty-four (34%) HIV
infected and 26 (44%) uninfected adolescents reported having ever smoked
cigarettes or drunk alcohol (p = 0.13); 10% of HIV-infected and 17% of uninfected
adolescents reported having initiated sexual activity; 6 of the HIV-infected
adolescents had HIV-RNA >1000 copies/mL. Risk behaviors were common among
adolescents, with few differences between those with and without HIV.
PMID- 29336592
TI - Changes in Body Mass Index, Leptin, and Leptin Receptor Polymorphisms and Breast
Cancer Risk.
AB - Obesity is a strong risk factor for breast cancer. The polymorphisms of leptin
(LEP) and leptin receptor (LEPR) may be associated with breast cancer by
regulator of adipose tissue mass and tumor cell growth. A total of 794 cases and
805 matched controls were sequentially enrolled. Time-of-flight mass spectrometry
was used to determine the LEPrs7799039, LEPRrs1137100, and LEPRrs1137101
genotypes for each participant. Associations between polymorphisms of these
genes, change in body mass index (BMI), and breast cancer risk were assessed by
unconditional multivariable logistic regression models. The unconditional
logistic regression model showed that persistent overweight (BMI >=24 kg/m2) over
the preceding 10 years was associated with increased breast cancer risk in
premenopausal women (odds ratio [OR] = 1.67, 95% confidence interval [CI]: 1.19
2.35). No associations between LEPrs7799039, LEPRrs1137100, or LEPRrs1137101
polymorphisms alone and breast cancer risk were found. Persistent overweight over
the preceding 10 years and carrying the LEPrs7799039 AA genotype together
increased breast cancer risk in premenopausal women (ORadj = 2.00, 95% CI: 1.26
3.16). Persistent overweight over the preceding 10 years and carrying the
LEPRrs1137100 GG genotype increased breast cancer risk in premenopausal women
(ORadj = 1.68, 95% CI: 1.06-2.68). In premenopausal women, persistent overweight
(BMI >=24 kg/m2) over the preceding 10 years increases breast cancer risk.
Persistent overweight along with LEPrs7799039 AA or LEPRrs1137100 GG genotypes
synergistically increase risk of breast cancer among premenopausal women.
PMID- 29336593
TI - Effect of vitamin A supplementation on iron status in humans: A systematic review
and meta-analysis.
AB - Anemia is a worldwide public health problem that can be related to many causes,
including vitamin A deficiency. The aim of this study was to assess and estimate
the effect of vitamin A supplementation (VAS) on iron status biomarkers and
anemia in humans. Six databases, including Cochrane, EMBASE, LILACS, Pubmed,
Scopus and Web of Science, were searched for clinical trials and cohort studies
that investigated the effect of vitamin A supplementation alone on iron status
and anemia, without time-restriction. The search yielded 23 eligible studies, 21
clinical trials and 2 cohort studies, with children, teenagers, pregnant or
lactating women. The meta-analysis of the clinical trials showed that VAS reduces
the risk of anemia by 26% and raises hemoglobin levels, compared to non-treated
group, independent of the life stage. VAS did not alter the prevalence of iron
deficiency among the clinical trials conducted with children and teenagers (RR
0.82, 95% CI 0.60 to 1.12, p = 0.204), whereas a significant increase in serum
ferritin levels was observed in trials conducted with pregnant and lactating
women (WMD 6.61 MUg/L; 95% CI 6.00 to 7.21 MUg/L; p < 0.001). Therefore, vitamin
A supplementation alone may reduce the risk of anemia, by improving hemoglobin
and ferritin levels in individuals with low serum retinol levels.
PMID- 29336595
TI - Exploitation of microbial antagonists for the control of postharvest diseases of
fruits: a review.
AB - Fungal diseases result in significant losses of fruits and vegetables during
handling, transportation and storage. At present, post-production fungal spoilage
is predominantly controlled by using synthetic fungicides. Under the global
climate change scenario and with the need for sustainable agriculture, biological
control methods of fungal diseases, using antagonistic microorganisms, are
emerging as ecofriendly alternatives to the use of fungicides. The potential of
microbial antagonists, isolated from a diversity of natural habitats, for
postharvest disease suppression has been investigated. Postharvest biocontrol
systems involve tripartite interaction between microbial antagonists, the
pathogen and the host, affected by environmental conditions. Several modes for
fungistatic activities of microbial antagonists have been suggested, including
competition for nutrients and space, mycoparasitism, secretion of antifungal
antibiotics and volatile metabolites and induction of host resistance.
Postharvest application of microbial antagonists is more successful for efficient
disease control in comparison to pre-harvest application. Attempts have also been
made to improve the overall efficacy of antagonists by combining them with
different physical and chemical substances and methods. Globally, many microbe
based biocontrol products have been developed and registered for commercial use.
The present review provides a brief overview on the use of microbial antagonists
as postharvest biocontrol agents and summarises information on their isolation,
mechanisms of action, application methods, efficacy enhancement, product
formulation and commercialisation.
PMID- 29336594
TI - Incorporating Whole-Genome Sequencing into Public Health Surveillance: Lessons
from Prospective Sequencing of Salmonella Typhimurium in Australia.
AB - In Australia, the incidence of Salmonella Typhimurium has increased dramatically
over the past decade. Whole-genome sequencing (WGS) is transforming public health
microbiology, but poses challenges for surveillance. To compare WGS-based
approaches with conventional typing for Salmonella surveillance, we performed
concurrent WGS and multilocus variable-number tandem-repeat analysis (MLVA) of
Salmonella Typhimurium isolates from the Australian Capital Territory (ACT) for a
period of 5 months. We exchanged data via a central shared virtual machine and
performed comparative genomic analyses. Epidemiological evidence was integrated
with WGS-derived data to identify related isolates and sources of infection, and
we compared WGS data for surveillance with findings from MLVA typing. We found
that WGS data combined with epidemiological data linked an additional 9% of
isolates to at least one other isolate in the study in contrast to MLVA and
epidemiological data, and 19% more isolates than epidemiological data alone.
Analysis of risk factors showed that in one WGS-defined cluster, human cases had
higher odds of purchasing a single egg brand. While WGS was more sensitive and
specific than conventional typing methods, we identified barriers to uptake of
genomic surveillance around complexity of reporting of WGS results, timeliness,
acceptability, and stability. In conclusion, WGS offers higher resolution of
Salmonella Typhimurium laboratory surveillance than existing methods and can
provide further evidence on sources of infection in case and outbreak
investigations for public health action. However, there are several challenges
that need to be addressed for effective implementation of genomic surveillance in
Australia.
PMID- 29336596
TI - HIV-related thought avoidance, sexual risk, and alcohol use among men who have
sex with men.
AB - HIV-related "cognitive escape" refers to a tendency to avoid thoughts associated
with HIV, which may be particularly common among men who have sex with men (MSM)
who are often inundated with HIV information, potentially to the point of
fatigue. HIV-related cognitive escape is associated with increased sexual risk
behaviors, such as condomless sex, and heavier alcohol use patterns. Other
studies show that some MSM may use alcohol specifically to facilitate sex. These
sexual motives for drinking (SMDs) could be one mechanism whereby cognitive
escape leads to health risk behaviors. In this study, we tested models exploring
whether cognitive escape was associated with markers of sex risk (condom use,
number of sex partners) and alcohol use/problems, and examined whether SMDs
mediated these associations. Heavy drinking, HIV-negative men (N = 196) aged >=
21 years who self-reported past year condomless anal sex with men completed
assessments as part of a larger study. Results suggest that cognitive escape was
associated with higher number of anal sex partners (incidence rate ratio [IRR] =
1.50, SE = 0.04, p < .001), decreased condom use (B = -0.30, SE = 0.14, p =
.028), and increased alcohol-related problems (IRR = 1.28, SE = 0.07, p = .001)
but not with drinking quantity. Sexual motives for drinking appeared to partially
mediate the observed relationship between cognitive escape and alcohol-related
problems, but other relationships did not show evidence of mediation. Findings
suggest that those who tend to avoid HIV-related thoughts may be at increased
risk for HIV and alcohol-related problems. Drinking to facilitate sex may
partially account for the higher risk for alcohol-related problems conferred by
cognitive escape. Alcohol interventions for MSM may be more effective if they
address alcohol's role in coping with HIV threat and in facilitating sex under
these circumstances.
PMID- 29336597
TI - Navigating emotions and relationship dynamics: family life review as a clinical
tool for older adults during a relocation transition into an assisted living
facility.
AB - OBJECTIVE: Relocation for the purpose of receiving care may be one of the more
challenging transitions for older adults. The purpose of this study was to
facilitate a family life review (FLR) session aimed at enhancing family
relationships and assisting older adults in coping with the challenges associated
with a relocation. METHODS: Fourteen dyads comprised of older adults who
relocated to an assisted living facility (ALF) and a chosen family member or
friend participated in a FLR session and semi-structured follow up interview.
Data were analyzed using the constant comparative method and triangulated with
descriptive statistics. RESULTS: Emergent themes suggested participating in FLR
influenced families by raising emotions, systemically thinking, and navigating
the relocation. FLR facilitated positive connections, enhanced existing
relationships, and promoted self-acceptance. Families indicated mutual
storytelling was enjoyable and reminded them of the urgency to share their story.
FLR allowed dyads to reflect and thus prompted a renewed perspective on some of
the more challenging components of the relocation transition. CONCLUSION: Study
findings provide insight into how families organize individual and interpersonal
narratives and use these narratives during transitional times. FLR can aid
families in making a smoother and fulfilling move to an ALF and other late life
transitions.
PMID- 29336598
TI - Quantitative MR Evaluation of Chronic Pancreatitis: Extracellular Volume Fraction
and MR Relaxometry.
AB - OBJECTIVE: The purpose of this study was to determine if extracellular volume
fraction and T1 mapping can be used to diagnose chronic pancreatitis (CP).
MATERIALS AND METHODS: This HIPAA-compliant study analyzed 143 consecutive
patients with and without CP who underwent MR imaging between May 2016 and
February 2017. Patients were selected for the study according to inclusion and
exclusion criteria that considered history and clinical and laboratory findings.
Eligible patients (n = 119) were grouped as normal (n = 60) or with mild (n =
22), moderate (n = 27), or severe (n = 10) CP on the basis of MRCP findings using
the Cambridge classification as the reference standard. T1 maps were acquired in
unenhanced and late contrast-enhanced phases using a 3D dual flip-angle gradient
echo sequence. All patients were imaged on the same 3-T scanner using the same
imaging parameters, contrast agent, and dosage. RESULTS: Mean extracellular
volume fractions and T1 relaxation times were significantly different within the
study groups (one-way ANOVA, p < 0.001). Using the AUC curve analysis,
extracellular volume fraction of > 0.27 showed 92% sensitivity (54/59) and 77%
specificity (46/60) for the diagnosis of CP (AUC = 0.90). A T1 relaxation time of
> 950 ms revealed 64% sensitivity (38/59) and 88% specificity (53/60) (AUC =
0.80). Combining extracellular volume fraction and T1 mapping yielded sensitivity
of 85% (50/59) and specificity of 92% (55/60) (AUC = 0.94). CONCLUSION:
Extracellular volume fraction and T1 mapping may provide quantitative metrics for
determining the presence and severity of acinar cell loss and aid in the
diagnosis of CP.
PMID- 29336599
TI - Femoral Neck Stress Injuries: Analysis of 156 Cases in a U.S. Military Population
and Proposal of a New MRI Classification System.
AB - OBJECTIVE: The objective of this study is to formulate a new MRI classification
system for fatigue-type femoral neck stress injuries (FNSIs) that is based on
patient management and return-to-duty (RTD) time. MATERIALS AND METHODS: A
retrospective review of 156 consecutive FNSIs in 127 U.S. Army soldiers over a 24
month period was performed. The width of marrow edema for low-grade FNSIs and the
measurement of macroscopic fracture as a percentage of femoral neck width for
high-grade FNSIs were recorded. RTD time was available for 90 soldiers.
Nonparametric testing, univariate linear regression, and survival analysis on RTD
time were used in conjunction with patient management criteria to develop a new
FNSI MRI classification system. RESULTS: The FNSI incidence was 0.09%, and all
FNSIs were compressive-sided injuries. RTD time was significantly longer for high
grade FNSIs versus low-grade FNSIs (p < 0.001). Our FNSI MRI classification
system showed a significant difference in RTD time between grades 1 and 2 (p =
0.001-0.029), 1 and 3 (p < 0.001), and 1 and 4 (p = 0.001-0.01). There was no
significant RTD time difference between the remaining grades. The rates of
completing basic training (BT) and requiring medical discharge were significantly
associated with the FNSI MRI grades (p = 0.038 and p = 0.001, respectively).
CONCLUSION: The proposed FNSI MRI classification system provides a robust
framework for patient management optimization by permitting differentiation
between operative and nonoperative candidates, by allowing accurate prediction of
RTD time, and by estimating the risk of not completing BT and requiring medical
discharge from the military.
PMID- 29336600
TI - Current Clinical Practice Patterns of Self-Identified Interventional
Radiologists.
AB - OBJECTIVE: The purpose of this study was to assess patterns of procedural,
clinical evaluation and management (E/M), and diagnostic imaging services
rendered by self-identified interventional radiologists (IRs) across the United
States. MATERIALS AND METHODS: Recent Medicare Physician and Other Supplier
Public Use and Physician Compare national downloadable files were linked. IRs
were defined as physicians self-identifying interventional radiology as their
primary specialty on Medicare claims or as a specialty during Medicare
enrollment. The primary outcome measure was percentage of work (in work relative
value units [WRVU]) attributed to interventional services (both procedural and
E/M) per IR. Secondary outcome measures included sociodemographic factors per
interventional WRVU quartile and percentage of E/M service units per IR.
Statistical analysis included chi-square and t tests and logistic regression.
RESULTS: Overall, 3132 physicians nationally self-identified to Medicare as IRs.
The distribution of WRVU attributed to interventional services was strongly
bimodal. Procedures and E/M together accounted for >= 91% and <= 5% of total work
for the most and least intervention-oriented quartiles, respectively, but were
widely distributed in the middle two quartiles. The most intervention-oriented
self-identified IRs were more likely out of medical school <= 30 years (odds
ratio [OR], 2.5; p < 0.0001), men (OR, 2.2; p < 0.0001), and in academic practice
(OR, 4.3; p < 0.0001). E/M accounted for only 1.4% of all billed services.
CONCLUSION: Although most self-identified IRs perform both interventional and
diagnostic imaging services, the subspecialty distribution is strongly bimodal,
one-quarter each focusing <= 5% and >= 91% of work on interventional services.
Despite ongoing emphasis on clinically focused interventional radiology, E/M
services remain rarely reported.
PMID- 29336601
TI - JOURNAL CLUB: Computer-Aided Detection of Lung Nodules on CT With a Computerized
Pulmonary Vessel Suppressed Function.
AB - OBJECTIVE: The purpose of this study is to evaluate radiologists' performance in
detecting actionable nodules on chest CT when aided by a pulmonary vessel image
suppressed function and a computer-aided detection (CADe) system. MATERIALS AND
METHODS: A novel computerized pulmonary vessel image-suppressed function with a
built-in CADe (VIS/CADe) system was developed to assist radiologists in
interpreting thoracic CT images. Twelve radiologists participated in a
comparative study without and with the VIS/CADe using 324 cases (involving 95
cancers and 83 benign nodules). The ratio of nodule-free cases to cases with
nodules was 2:1 in the study. Localization ROC (LROC) methods were used for
analysis. RESULTS: In a stand-alone test, the VIS/CADe system detected 89.5% and
82.0% of malignant nodules and all nodules no smaller than 5 mm, respectively.
The false-positive rate per CT study was 0.58. For the reader study, the mean
area under the LROC curve (LROCAUC) for the detection of lung cancer
significantly increased from 0.633 when unaided by VIS/CADe to 0.773 when aided
by VIS/CADe (p < 0.01). For the detection of all clinically actionable nodules,
the mean LROC-AUC significantly increased from 0.584 when unaided by VIS/CADe to
0.692 when detection was aided by VIS/CADe (p < 0.01). Radiologists detected
80.0% of cancers with VIS/CADe versus 64.45% of cancers unaided (p < 0.01);
specificity decreased from 89.9% to 84.4% (p < 0.01). Radiologist interpretation
time significantly decreased by 26%. CONCLUSION: The VIS/CADe system
significantly increased radiologists' detection of cancers and actionable nodules
with somewhat lower specificity. With use of the VIS/CADe system, radiologists
increased their interpretation speed by a factor of approximately one-fourth. Our
study suggests that the technique has the potential to assist radiologists in the
detection of additional actionable nodules on thoracic CT.
PMID- 29336602
TI - Surface Spectroscopic Signatures of Mechanical Deformation in High-Density
Polyethylene (HDPE).
AB - High-density polyethylene (HDPE) has been extensively studied, both as a model
for semi-crystalline polymers and because of its own industrial utility. During
cold drawing, crystalline regions of HDPE are known to break up and align with
the direction of tensile load. Structural changes due to deformation should also
manifest at the surface of the polymer, but until now, a detailed molecular
understanding of how the surface responds to mechanical deformation has been
lacking. This work establishes a precedent for using vibrational sum-frequency
generation (VSFG) spectroscopy to investigate changes in the molecular-level
structure of the surface of HDPE after cold drawing. X-ray diffraction (XRD) was
used to confirm that the observed surface behavior corresponds to the expected
bulk response. Before tensile loading, the VSFG spectra indicate that there is
significant variability in the surface structure and tilt of the methylene groups
away from the surface normal. After deformation, the VSFG spectroscopic
signatures are notably different. These changes suggest that hydrocarbon chains
at the surface of visibly necked HDPE are aligned with the direction of loading,
while the associated methylene groups are oriented with the local C2v symmetry
axis roughly parallel to the surface normal. Small amounts of unaltered material
are also found at the surface of necked HDPE, with the relative amount of
unaltered material decreasing as the amount of deformation increases. Aspects of
the nonresonant SFG response in the transition zone between necked and undeformed
polymer provide additional insight into the deformation process and may provide
the first indication of mechanical deformation. Nonlinear surface spectroscopy
can thus be used as a noninvasive and nondestructive tool to probe the stress
history of a HPDE sample in situations where X-ray techniques are not available
or not applicable. Vibrational sum-frequency generation thus has great potential
as a platform for material state awareness (MSA) and should be considered as part
of a broader suite of tools for such applications.
PMID- 29336603
TI - Comparison of Unlicensed and Off-Label Use of Antipsychotics Prescribed to Child
and Adolescent Psychiatric Outpatients for Treatment of Mental and Behavioral
Disorders with Different Guidelines: The China Food and Drug Administration
Versus the FDA.
AB - OBJECTIVES: This study aims to compare the prevalence of unlicensed and off-label
use of antipsychotics among child and adolescent psychiatric outpatients with
guidelines proposed by the China Food and Drug Administration (CFDA) and the U.S.
Food and Drug Administration (FDA), and to identify factors associated with
inconsistencies between the two regulations. METHODS: A retrospective analysis of
29,326 drug prescriptions for child and adolescent outpatients from the
Affiliated Brain Hospital of Guangzhou Medical University was conducted.
Antipsychotics were classified as "unlicensed" or "off-label use" according to
the latest pediatric license information registered by the CFDA and the FDA or
the package inserts of antipsychotics authorized by the CFDA or the FDA for the
treatment of pediatric mental and behavioral disorders, respectively. Binary
logistic regression analysis was performed to assess factors associated with
inconsistencies between the two regulations. RESULTS: The total unlicensed use,
according to the CFDA analysis, was higher than that found in the FDA analysis
(74.14% vs. 22.04%, p < 0.001). However, the total off-label use, according to
the FDA analysis, was higher than that found in the CFDA analysis (46.53% vs.
15.77%, p < 0.001). Antipsychotic drug classes, age group, number of diagnoses,
and diagnosis of schizophrenia and schizotypal and delusional disorders were
associated with inconsistent unlicensed use. Antipsychotic drug classes, age
group, number of prescribed psychotropic drugs, gender, diagnosis of
schizophrenia and schizotypal and delusional disorders, diagnosis of mood
[affective] disorders, diagnosis of mental retardation, and diagnosis of
psychological development disorders were associated with inconsistent off-label
use. CONCLUSIONS: The difference in prevalence of total unlicensed and off-label
use of antipsychotics between the two regulations was statistically significant.
This inconsistency could be partly attributed to differences in pediatric license
information and package inserts of antipsychotics. The results indicate a need
for further clinical pediatric studies and better harmonization between agencies
regarding antipsychotic used in pediatrics.
PMID- 29336604
TI - Family Functioning and Mental Health of Transgender and Gender-Nonconforming
Youth in the Trans Teen and Family Narratives Project.
AB - Transgender and gender-nonconforming (TGN) youth are at increased risk for
adverse mental health outcomes, but better family functioning may be protective.
This study describes TGN youth's mental health and associations with family
functioning in a community-based sample. Participants were from 33 families (96
family members) and included 33 TGN youth, ages 13 to 17 years; 48 cisgender (non
transgender) caregivers; and 15 cisgender siblings. Participants completed a
survey with measures of family functioning (family communication, family
satisfaction) and mental health of TGN youth (suicidality, self-harm, depression,
anxiety, self-esteem, resilience). TGN youth reported a high risk of mental
health concerns: suicidality (15% to 30%), self-harm (49%), clinically
significant depressive symptoms (61%); and moderate self-esteem (M = 27.55, SD =
7.15) and resiliency (M = 3.67, SD = 0.53). In adjusted models, better family
functioning from the TGN youth's perspective was associated with better mental
health outcomes among TGN youth (beta ranged from -0.40 to -0.65 for self-harm,
depressive symptoms, and anxious symptoms, and 0.58 to 0.70 for self-esteem and
resiliency). Findings from this study highlight the importance of considering TGN
youth's perspectives on the family to inform interventions to improve family
functioning in families with TGN youth.
PMID- 29336606
TI - Update on Molecular Testing for Cytologically Indeterminate Thyroid Nodules.
AB - CONTEXT: - Approximately 15% to 30% of thyroid nodules that undergo fine-needle
aspiration are classified as cytologically indeterminate, presenting management
challenges for patients and clinicians alike. During the past several years,
several molecular tests have been developed to reduce the diagnostic uncertainty
of indeterminate thyroid fine-needle aspirations. OBJECTIVE: - To review the
methodology, clinical validation, and recent peer-reviewed literature for 4
molecular tests that are currently marketed for cytologically indeterminate
thyroid fine-needle aspiration specimens: Afirma, ThyroSeq, ThyGenX/ThyraMIR, and
RosettaGX Reveal. DATA SOURCES: - Peer-reviewed literature retrieved from PubMed
search, data provided by company websites and representatives, and authors'
personal experiences. CONCLUSIONS: - The 4 commercially available molecular tests
for thyroid cytology offer unique approaches to improve the risk stratification
of thyroid nodules. Familiarity with data from the validation studies as well as
the emerging literature about test performance in the postvalidation setting can
help users to select and interpret these tests in a clinically meaningful way.
PMID- 29336605
TI - Colorectal Carcinomas With Isolated Loss of PMS2 Staining by
Immunohistochemistry.
AB - CONTEXT: - Isolated loss of PMS2 staining is an uncommon immunophenotype in
colorectal carcinomas, accounting for approximately 4% of tumors with
microsatellite instability. Limited information regarding these tumors is
available in the literature. OBJECTIVE: - To compare the clinicopathologic
features of colorectal carcinomas with isolated PMS2 loss by immunohistochemistry
to those with other forms of mismatch repair deficiency. DESIGN: - Ninety-three
colorectal carcinomas with isolated PMS2 loss by immunohistochemistry and 193
with other forms of mismatch repair deficiency were identified. Forty (43%) of
the isolated PMS2 loss cases and 35 control cases (18%) had a known germline
mutation or a clinical diagnosis of Lynch syndrome. RESULTS: - Overall, isolated
PMS2-loss tumors occurred in significantly younger patients ( P < .001) and in
fewer female patients ( P = .006). These tumors were significantly less likely to
be right-sided ( P = .001), high-grade ( P = .01), or display histologic features
of microsatellite instability ( P < .001). The isolated PMS2-loss group also
exhibited increased odds of disease-specific death (odds ratio [OR], 3.09; 95%
CI, 1.41-6.85; P = .007). When the analysis was restricted to germline
mutation/Lynch syndrome cases and controls, no significant differences were
detected for age, sex, tumor location, tumor grade, histologic features, or
distant metastases, although a trend toward increased odds of disease-specific
death in the isolated PMS2-loss group was evident (OR, 3.87; 95% CI, 0.89-27.04;
P = .10). CONCLUSIONS: - Unusual clinicopathologic features observed in
colorectal carcinomas with isolated PMS2 loss are likely related to the high
proportion of cases caused by germline mutations. Isolated PMS2-loss tumors may
demonstrate more aggressive behavior than other tumors with microsatellite
instability, but larger studies are needed to investigate that possibility
further.
PMID- 29336607
TI - Alu siRNA to increase Alu element methylation and prevent DNA damage.
AB - : Global DNA hypomethylation promoting genomic instability leads to cancer and
deterioration of human health with age. AIM: To invent a biotechnology that can
reprogram this process. METHODS: We used Alu siRNA to direct Alu interspersed
repetitive sequences methylation in human cells. We evaluated the correlation
between DNA damage and Alu methylation levels. RESULTS: We observed an inverse
correlation between Alu element methylation and endogenous DNA damage in white
blood cells. Cells transfected with Alu siRNA exhibited high Alu methylation
levels, increased proliferation, reduced endogenous DNA damage and improved
resistance to DNA damaging agents. CONCLUSION: Alu methylation stabilizes the
genome by preventing accumulation of DNA damage. Alu siRNA could be useful for
evaluating reprograming of the global hypomethylation phenotype in cancer and
aging cells.
PMID- 29336608
TI - Prevalence of frailty and its association with depressive symptoms among older
adults in Singapore.
AB - OBJECTIVES: The aims of the study were to (1) estimate the prevalence of frailty
among community-dwelling older adults , and (2) investigate the independent
association between level of frailty and depressive symptoms. METHODS: A total of
721 older adults (aged 60 and above ) were included in this study. Severity of
frailty was determined using the Clinical Frailty Scale and further classified
into four levels (CFS1-3: F1, CFS4: F2, CFS5: F3, and CFS6-7: F4). The depressive
symptoms were assessed using the Patient Health Questionnaire-9. The prevalence
of frailty by four levels was described and the association between level of
frailty and depressive symptoms was assessed using multiple linear regression.
RESULTS: The prevalence of frailty among the study population was 24.5% (F2:
14.4%, F3:3.7%, F4: 6.4%). There was no significant difference in level of
frailty between male and female. With the increase in severity level of frailty,
older adults reported substantially higher depressive symptom scores (p < .001),
even after controlling for socio-demographics, number of non-mental chronic
conditions, and number of medications taken regularly. CONCLUSIONS: Level of
frailty is independently associated with depressive symptoms among community
dwelling older population, which is not fully explained by symptom overlap, socio
demographic, and comorbidity covariates.
PMID- 29336609
TI - Fibroblast growth factor 23 (FGF23) gene polymorphisms are associated with
essential hypertension risk and blood pressure levels in Chinese Han population.
AB - In this case-control study, 246 EH patients and 157 healthy controls were
selected from Chinese Han population to explore the associations between the
fibroblast growth factor 23 (FGF23) gene polymorphisms and essential hypertension
(EH).The SequenomMassarray system was used for the genotyping of three FGF23 gene
Tag single-nucleotide polymorphisms, namely rs7955866, rs13312756, and rs3812822.
The primers were designed by Assay Designer 3.1 software, and then the samples
were added to a 384-well plate for the polymerase chain reaction amplification,
shrimp alkaline phosphatase reaction, and desalting after extension. The
distributions of the alleles, genotypes, and haplotypes were compared between the
two groups. Confounding factors (sex, age, BMI, smoking, and drinking) were
adjusted in the non-logistic regression, and the results showed that rs7955866
and rs3812822 polymorphisms were independently associated with the risk of
developing EH (P < 0.05). The statistical analysis of the haplotype of rs7955866
rs13312756-rs3812822 showed that haplotype ACC could increase the risk of
developing EH (P = 0.046; OR = 1.513, 95%CI: 1.005-2.278). The analysis of the
control group showed that carrying rs7955866 A allele (P = 0.031) and rs3812822 C
allele (P = 0.025) was associated with the increase of systolic blood pressure
(SBP). The insulin (INS) level in the peripheral blood was significantly
different between the case and control groups (P = 0.014). After confounding
factors were excluded, the results showed that the serum INS level was also an
independent risk factor of developing EH (P = 0.044; OR = 1.604, 95%CI: 1.014
2.539). In summary, our results suggest that FGF23 gene polymorphisms are
associated with the risk of developing EH in Chinese Han population.
PMID- 29336610
TI - NrF2/ARE and NF-kappaB pathway regulation may be the mechanism for lutein
inhibition of human breast cancer cell.
AB - AIM: Though lutein can inhibit cancer cell proliferation via alleviating
oxidative injury, the molecular mechanisms of lutein involvement in the
NrF2/antioxidant response element (ARE) and NF-kappaB pathways remain poorly
understood. MATERIALS & METHODS: MTT, flow cytometry, quantitative real-time PCR
(qRT-PCR) and western blot assays were performed. RESULTS: After treatment with
lutein, breast cancer cell proliferation was significantly decreased in a dose
dependent manner. Lutein induced nuclear translocation and protein expression of
NrF2, improved the expression of cellular antioxidant enzymes and attenuated
reactive oxygen species levels. Moreover, lutein treatment decreased NF-kappaB
signaling pathway related NF-kappaB p65 protein expression. CONCLUSION: The
effect of lutein antiproliferation was mediated by activation of the NrF2/ARE
pathway, and blocking of the NF-kappaB signaling pathway.
PMID- 29336611
TI - Interventions to improve benzodiazepine tapering success in the elderly: a
systematic review.
AB - BACKGROUND: Long-term benzodiazepine use in the elderly population is a
significant public health problem that leads to impaired cognitive functioning,
medication dependence and increased risks for adverse drug reactions. The aim of
this review was to examine randomized controlled trials (RCTs) on the efficacy of
different methods for tapering and discontinuing benzodiazepines. METHOD: We used
four databases (Ovid, PubMed, Academic Search Complete, Web of Science) to
retrieve randomized controlled trials published in peer-reviewed journals that
explored different methods for tapering benzodiazepine use in a primarily
geriatric population. RESULTS: Eleven papers met the inclusion criteria. Methods
to assist in benzodiazepine tapering included patient education, cognitive
behavioural therapy (CBT), and pharmaceutical adjuvants (SSRIs, melatonin,
progesterone). Patient education was consistently effective in increasing
benzodiazepine discontinuation success while CBT had mixed but promising results.
The use of medications to help improve tapering success was inconclusive.
CONCLUSIONS: Patient education is a successful, time- and cost-effective
intervention that can significantly help with benzodiazepine discontinuation
success. CBT may also be an effective approach. However, cost can be an issue
since public healthcare coverage in Canada does not cover psychotherapy. More
research is needed in looking at pharmaceutical adjuvants and their role in
assisting with benzodiazepine discontinuation.
PMID- 29336613
TI - Breastfeeding: The Road Less Traveled.
PMID- 29336612
TI - Relationship among adiponectin, insulin resistance and atherosclerosis in non
diabetic hypertensive patients and healthy adults.
AB - Adiponectin, which is secreted specifically by adipose tissue, has been shown to
have anti-atherogenic and anti-inflammatory effects and to improve insulin
resistance (IR). The aim of this study was to determine the correlations among
adiponectin, IR and atherosclerosis in non-diabetic hypertensive patients and
healthy volunteers. In this case control study, we collected complete demographic
data from and measured several laboratory parameters in all enrolled subjects.
The homeostasis model of assessment for insulin resistance (HOMA-IR) was
calculated as an insulin sensitivity index. The atherogenic index of plasma
(AIP), which is calculated as log (triglyceride (TG)/high-density lipoprotein
cholesterol (HDL-C)), was a significant predictor of atherosclerosis and was a
better predictor of atherosclerosis than low-density lipoprotein cholesterol (LDL
C). Plasma adiponectin, interleukin (IL)-6, monocyte chemoattractant protein-1
(MCP-1) and matrix metalloprotein-9 (MMP-9) concentrations were determined using
enzyme-linked immunosorbent assay (ELISA). All data were analyzed using
Statistical Product and Service Solutions for Windows (SPSS) 13.0 software. A
total of 309 participants were enrolled in the study. Hypertensive patients with
IR (n = 93) displayed significantly higher HOMA-IR values and AIPs and lower
adiponectin levels than hypertensive patients without IR (n = 121) and healthy
adults (n = 95) (P < 0.05). Furthermore, circulating IL-6, MCP-1 and MMP-9
concentrations differed significantly between hypertensive patients and healthy
adults (P < 0.05). Additionally, adiponectin levels were found to be inversely
correlated with IL-6, MCP-1, and MMP-9 levels; HOMA-IR values; and AIPs in the
clinical study. HOMA-IR values and adiponectin and creatinine (Cr) concentrations
remained independently associated with AIPs in all participants after adjustment
for confounders via multivariate linear regression. Low adiponectin levels are
positively correlated with decreased insulin sensitivity, increased pro
inflammatory cytokine production and worsening atherosclerosis in hypertensive
patients and healthy adults.
PMID- 29336614
TI - Evaluation of Corneal Parameters with Dual Scheimpflug Imaging in Patients with
Systemic Sclerosis.
AB - PURPOSE: To evaluate the cornea of systemic sclerosis (SSc) patients with Dual
Scheimpflug Imaging. METHODS: Twenty consecutive SSc patients and 20 age and sex
matched controls were enrolled in this cross-sectional study. Corneal
measurements were acquired by dual Scheimpflug analyzer. RESULTS: SSc patients
had statistically significant steeper corneas than the control group. The mean
anterior curvature-average (SimK) was 44.93 +/- 1.64 D (mean +/- standard
deviation) in SSc and 43.61 +/- 0.99D in control group, p = 0.01. Posterior
curvature was also steeper in SSc patients compared to controls (p = 0.02). There
was no statistically significant difference regarding central average pachymetry
(p = 0.07), thinnest pachymetry (p = 0.09). CONCLUSIONS: Patients with SSc
present with steeper corneas than controls.
PMID- 29336615
TI - Pharmacokinetic bioequivalence, safety and acceptability of Ornibel(r), a new
polymer composition contraceptive vaginal ring (etonogestrel/ethinylestradiol
11.00/3.474 mg) compared with Nuvaring(r) (etonogestrel/ethinylestradiol 11.7/2.7
mg).
AB - OBJECTIVE: To show the clinical development of Ornibel(r) (ExeltisHealthcare,
Spain) a contraceptive vaginal ring manufactured with a new polymer composition
and containing etonogestrel/ethinylestradiol, compared to Nuvaring(r) (MSD,
Spain). SUBJECTS AND METHODS: Randomised, single dose, 2-period, 2-sequence, 2
stage crossover, comparative bioavailability study conducted in 40 healthy female
subjects. All subjects received both treatments for 28 days in each of two
periods, separated by a 28 days washout. Ornibel(r) contains
etonogestrel/ethinylestradiol 11.00/3.47 mg and Nuvaring(r) contains
etonogestrel/ethinylestradiol 11.7/2.7 mg, both rings delivering 120/15 ug/day.
For the calculation of pharmacokinetic parameters, 37 blood samples were
collected up to 840 h after each ring insertion to quantify plasma concentrations
of etonogestrel and ethinylestradiol using a validated MS/MS-HPLC. Safety was
assessed by adverse events recording, clinical laboratory and vital signs and
tolerability by vaginal examination. Acceptability was investigated by a 5-point
scale questionnaire. RESULTS: Bioequivalence was demonstrated in the first stage
as the 94.12% Confidence Intervals of the primary parameters laid within the 80
125% acceptance range for both etonogestrel (Cmax: 96.81-112.20%; AUC0-504h:
98.71-108.61%; AUC0-t: 100.14-109.10%) and ethinylestradiol. (Cmax: 105.91
120.62%; AUC0-504h: 105.47-114.59%; AUC0-t: 108.31-117.61%). During the first day
of use a burst effect was observed with Nuvaring(r), with significantly higher
level of ethinylestradiol (Cmax0-24h ratio: 78.34%, 94.12CI: 73.55-83.45%). Both
products were well tolerated and accepted, without significant differences
between them. CONCLUSION: Ornibel(r) is bioequivalent to Nuvaring(r) in terms of
efficacy, safety, tolerability and acceptability. The new polymer composition
provides Ornibel(r) with more stability and gradual hormonal release during the
first day of use, particularly for ethinylestradiol.
PMID- 29336616
TI - Study of the osteoprotegerin/receptor activator of nuclear factor-kB ligand
system association with inflammation and atherosclerosis in systemic sclerosis.
AB - OBJECTIVE: we aimed to study systemic sclerosis patients in order to assess
osteoprotegerin/Receptor activator of nuclear factor-kB ligand (OPG/RANKL) system
and find the relation of these biomarkers with the clinical features of the
disease, the carotid intima thickness, markers of inflammation, lipid profile,
and other laboratory characteristics. METHODS: both the level of (RANKL), (OPG)
in sera of participants, in 30 (SSc) patients and the atherosclerotic changes
affecting the common carotid artery were measured and, were compared to 30
healthy controls matched for age and sex. All participants were assessed
clinically and subjected to the Revised Medsger SSc severity scale and underwent
carotid Doppler ultrasound examination. RESULTS: OPG, RANKL, and RANKL/OPG were
1.9 +/- 0.4 ng/ml, 24.3 +/- 17.25 ng/ml, and 13.5 +/-9.8 versus 0.77 +/- 0.25
ng/ml, 7.13 +/- 3.02 ng/ml, and 9.6 +/- 3.1 in the SSc patients and the controls
with significance (P = 0.001, P = 0.001, P = 0.045) respectively. The OPG- RANKL
axis in the SSc patients correlated significantly with carotid intima thickness,
arthritis, arthralgia, inflammatory markers, Medsger joint, Medsger vascular,
Medsger skin, and dyslipidemia. CONCLUSION: In cardiovascular risks, OPG serum
level might increase as a preventive compensatory mechanism to neutralize the
RANKL level increment. The determination of the OPG-RANKL system is a diagnostic
indicator for the intensity of vascular calcification and atherosclerosis in SSc
patients.
PMID- 29336617
TI - Incidental neuroblastoma with bilateral retinoblastoma: what are the chances?
AB - A child with bilateral familial retinoblastoma underwent staging MRI brain and
orbit which identified subtle leptomeningeal enhancement, thus prompting an MRI
whole body, which revealed a retroperitoneal mass, confirmed on laparoscopic
biopsy to be neuroblastoma. This is the first reported case of these two rare
embryonal non-central nervous system tumors occurring concurrently. The cause of
this concurrence is unknown despite their pathogenic similarities with a chance
of 4 cases per 10 billion children aged 1-4 years. Incidental neuroblastomas in
infants can regress spontaneously but this child underwent systemic chemotherapy
for his retinoblastoma that may have caused regression of the neuroblastoma.
PMID- 29336619
TI - Minimally Invasive Nerve-Sparing Radical Hysterectomy: A Win-Win Scenario.
PMID- 29336618
TI - Rheumatoid arthritis: A single-center Egyptian experience.
AB - OBJECTIVE: Demonstration of rheumatoid arthritis (RA) characteristics in a large
cohort of Egyptian patients. METHODS: Retrospective analysis of data of 3219 RA
patients attending the Rheumatology outpatient clinic, Kasr Alainy Hospital,
Cairo University; from January 1995 till December 2015. RESULTS: Mean age at
disease onset was 36.1 +/-13.4 years; 2774 (84%) were females and mean disease
duration was 12.9 +/-7.9 years. Regarding number of joint affected at disease
onset; polyarticular pattern was found in 77.1%, pattern of joint involvement;
combined small and large joints involvement was in 83.2%, subcutaneous nodules in
14.2%, interstitial lung disease in 0.3%, secondary Sjogren's syndrome in 10.5%,
hand bony erosions at diagnosis in 20.6%. Rheumatoid factor was positive in 52%.
There was annual increase in the newly diagnosed cases (P = 0.017) reflecting
increase in patients' awareness and improvement of medical service, also annual
increase in: mean age of onset (P < 0.001) reflecting changes in health measures,
also in cases with monoarticular or oligoarticular patterns at disease onset (P =
0.02, 0.01 respectively) reflecting earlier diagnosis of patients and in patients
with small joint involvement (P = 0.001) with a significant decline in:
polyarticular pattern (P = 0.001), combined small and large joint affection (P <
0.001), and number of cases with hand bony erosions (P = 0.01) denoting earlier
diagnosis, tight disease control. CONCLUSION: We found a female predominance,
younger age at disease onset, lower frequency of extra articular manifestations,
more frequent polyarticular pattern at disease onset and less erosive disease,
denoting changing referral patterns, earlier diagnosis, improved disease control
in Egyptian RA patients over 2 decades. ABBREVIATIONS: SNs: Subcutaneous nodules;
2ry SS: 2ry Sjogren's syndrome; ILD: Interstitial lung disease; ACPA: Anti-cyclic
citrullinated peptide antibodies; DMARDs: Disease modifying anti-rheumatic drugs.
PMID- 29336620
TI - The role of the PI3K/mTOR signaling pathway in Staphylococcus epidermidis small
colony variants intracellular survival.
AB - The objective of this study was to analyze how Staphylococcus epidermidis SCV and
WT strains manipulate the PI3K/Akt/mTOR signaling pathway. Six S. epidermidis
strains with normal phenotype (WT) and six S. epidermidis strains with SCV
phenotype were isolated in parallel from six patients with the prosthetic hip
joint infections. THP-1 activated cells were incubated with or without PI3K
inhibitor-wortmannin or with mTOR inhibitor-rapamycin. Next, macrophages were
exposed to S. epidermidis WT and SCV strains. After 4 h incubation, bacterial
survival inside macrophages as well as PI3K-mTOR activation was analyzed. SCV
strains of S. epidermidis increased the level of Akt phosphorylation, compared to
uninfected macrophages and to their parental WT forms. Wild type variants of S.
epidermidis phosphorylated Akt at similar or lower levels as control uninfected
cells. Next, the induction of mTOR target, phosphorylated ribosomal protein S6,
was measured in bacteria-infected macrophages. The level of phosphorylation was
significantly reduced when the cells were exposed to WT strains of S.
epidermidis. In contrast, the SCV strains activated S6 protein mostly at a level
comparable to the control cells. Rapamycin inhibited mTOR activation as the
number of p-S6 positive cells decreased in the tested cases. To conclude, the SCV
strains activate the PI3K-Akt signaling pathway in opposite to WT strains. This
fact however did not influence the increase in the number of live SCV bacteria as
compared to the WT strains. Knowing that the PI3K-Akt pathway is involved in
proinflammatory cytokines suppression, SCVs seem to use this pathway to reduce
the inflammatory response during the infection.
PMID- 29336621
TI - Beta-Alanine Does Not Enhance the Effects of Resistance Training in Older Adults.
AB - To investigate the potential of beta-alanine to increase muscular endurance of
elder individuals in specific resistance-training protocols, we randomly assigned
27 participants (60-82 years of age) to a 12-week double-blind intervention using
3.2 g/day beta-alanine or placebo with or without resistance training to
determine the effects on anthropometrics, muscular performance, and activities of
daily living (ADL). The endurance-based resistance-training program (ERT) was
given three times per week and included two sets of 15-25 repetitions on 11
computerized pneumatic machines (alternating upper and lower body) at an
intensity of 50% of maximum lifting weight (1RM). Mixed design analysis of
variance (ANOVA) revealed no significant group * time interactions (p > .05) for
any anthropometric or strength measures except 1RM leg press (p = .010). A post
hoc analysis revealed significant improvements in 1RM leg press for both the
resistance-training groups (p < .001) but no significant between-group difference
attributable to beta-alanine. For the 20-repetition chest and leg press tests, no
main effects of beta-alanine or group * time interactions for the exercise versus
control groups were observed. Pairwise comparisons, however, did reveal
significant improvements in peak and average power for both tests and fatigue
index for the chest press in resistance-training groups. Although beta-alanine
had no effect on any measures, the ERT program did positively affect three
performance variables: 1RM, mechanical power, and fatigue patterns during
muscular endurance testing. Future research should examine beta-alanine with
different dosages and training programs to expand upon our findings using
endurance-based resistance training.
PMID- 29336622
TI - Nutritional Supplement and Functional Food Use Among Medical Students in India.
AB - This study was conducted to assess the pattern of use of nutritional supplements
(NSs) and functional foods (FFs), reasons for their use, factors influencing
their use, and perception toward their use among medical students. Data were
collected from 400 randomly chosen participants using a self-administered
semistructured questionnaire. The most common source of information on these
substances was from medical professionals (n = 140 [35%]). Multivitamins were
consumed by 48 (45.3%) participants. Most common reasons stated for the use of
supplements were for good health (n = 39 [36.8%]), doctor's prescription (n = 36
[34%]), and to balance a poor diet (n = 34 [32.1%]). Sixty-six (62.3%) users used
NSs on a daily or more than once daily basis. In 17.9% of the users, supplements
were not recommended by a doctor or a dietician. The use of NSs was significantly
more among females (p < .001), participants who exercised regularly (p < .001),
participants who habitually skipped breakfast (p = 0.04), those with a family
history of use of these products (p < .001), and those with "poor to fair" self
rated health (p = .017). Use of FFs was associated with family history of use (p
< .001) and intensity of exercise (p = .039). Participants who significantly used
multiple NSs in this study were those who were vegetarians (p = .044) and those
with "poor to fair" self-rated health (p = .047). Participants who used multiple
FFs were female (p < .001). Only 18 (16.9%) users felt that regular use of NSs
results in side effects. In multivariate analysis, family history of NS use was
found to influence its usage among participants (p < 0.001). It is a matter of
concern that there is lack of knowledge on NSs and FFs among medical students.
Therefore, they need to learn more about the indications and the safety of
prescription of these products.
PMID- 29336623
TI - The Effect of Phytosterol-Rich Fraction from Palm Fatty Acid Distillate on Blood
Serum Lipid Profile of Dyslipidemia Rats.
AB - Phytosterol-rich fraction (PRF) obtained from palm fatty acid distillate (PFAD)
was investigated for its effect on blood serum lipid profile of dyslipidemia
rats. Dyslipidemia was induced by force feeding cholesterol to five groups of
rats; one group was a control or normal group. Cholesterol force-fed groups were
treated with 0, 10, 20, 30, and 40 mg PRF/kg/day for 4 weeks. All groups of rats
were fed standard diet. A normal group was fed standard diet without PRF
treatment and cholesterol force feeding. Lipid profile was measured every week
(0, 1, 2, 3, and 4). Four-week treatment resulted in significant blood serum
lipid profile improvement. PRF improved blood serum lipid profile by decreasing
total cholesterol, triglyceride, and low density lipoprotein (LDL) cholesterol
level and increasing high density lipoprotein (HDL) cholesterol level. The doses
of PRF significantly affected blood serum lipid profile as well as duration of
PRF treatment. PRF inhibited cholesterol absorption, which delayed blood serum
total cholesterol rise. Cholesterol absorption inhibition was also indicated by
higher fecal cholesterol concentration after PRF feeding. These results indicate
the beneficial effect of PRF in the treatment of dyslipidemia.
PMID- 29336624
TI - Potential Molecular Targets in the Treatment of Lung Cancer Using siRNA
Technology.
AB - Lung cancer is the leading cause of cancer-related mortality with about 1.6
million deaths every year worldwide. Gene mutations and overexpression of
oncogenes play a central role in malignant transformation in NSCLC. Conventional
approaches for treatments of NSCLC have shown low levels of success while showing
severe side effects. Target therapy using siRNA has recently emerged as a new
strategy for cancer treatment by specific targeting of genes involved in the
development and metastasis of cancer. This article dedicated to an update review
of molecular targets could potentially be used for target therapy of lung cancer
using SiRNA technology.
PMID- 29336625
TI - The Clavien-Dindo Classification in Pancreatic Surgery: A Clinical and Economic
Validation.
AB - BACKGROUND/AIMS: In 2004 P. A. Clavien and D. Dindo published the well-known
grading system of postoperative complications. It is established in several
surgical disciplines. The aim of this study was to assess its validity in
pancreatic surgery. The impact of complication grade on economic resources was
investigated as well. METHODS: From a prospective database, we retrospectively
evaluated all patients who underwent pancreatic resection between January 2009
and December 2014 at our department. 309 patients received pancreatic head
resection (pylorus-preserving pancreatoduodenectomy (PPPD) or Kausch-Whipple),
total pancreatectomy or left resection. We performed a univariate analysis of the
correlation between the Clavien-Dindo classification-grade (CDC-grade) with
length of postoperative stay (LOS) and DRG-related (diagnosis related groups)
remuneration using Kruskal-Wallis test. Furthermore, we performed a subgroup
analysis (chi-square test and Fishers-test) of demographic, clinical, and
perioperative data. RESULTS: American Society of Anesthesiologists (ASA) score (p
= 0.0014), operation time (p = 0.0229) and intraoperative blood loss (p = 0.0016)
showed significant correlation with CDC-grade. Increasing LOS and DRG-related
remuneration correlated significantly with increasing CDC-grade (p < 0.0001).
CONCLUSION: The CDC-grading system shows high correlation to clinical outcome and
case-related remuneration in pancreatic surgery. Therefore, it is a valid tool
for evaluation and comparison of surgical techniques and surgical centers.
PMID- 29336626
TI - Antihypertensive monotherapy or combined therapy: which is more effective on
functional status?
AB - BACKGROUND: This study aims to analyze the effects of anti-hypertensive
monotherapy and combined therapy on functional status, and cardiovascular risk
outcomes in older adults. METHODS: This longitudinal non-randomized cohort study,
involved hypertensive older adults (n = 440) aged 60 or more years with
comorbidities. Participants underwent a community exercise training program and
one of the following 2 conditions: i) use of daily mono-dose angiotensin
converting enzyme inhibitors (ACEi; n= 232); ii) combined therapy including ACEi
plus other class agent (Combined; n= 208). Baseline and 2-year follow-up
evaluations included the functional fitness, health-related quality of life
(HRQoL), health history questionnaires, anthropometric and hemodynamic profile.
RESULTS: Both experimental groups have significantly improved physical functional
status, and have significantly decreased blood pressure and waist circumference.
ACEi group has significantly reduced body mass and body mass index, the Combined
group significantly reduced the waist-to-hip ratio. Additionally, both groups
perceived better physical HRQoL. CONCLUSIONS: Functional status has improved with
ACEi medication and exercise training, regardless the ACEi medication therapy.
Exercise training plus ACEi antihypertensive therapy should be recommended into
the standard prescription practice to reduce the rate of physical disability
among hypertensive older adults.
PMID- 29336627
TI - Clinical Severity Classification using Automated Conjunctival Hyperemia Analysis
Software in Patients with Superior Limbic Keratoconjunctivitis.
AB - PURPOSE: Digitization of clinical observation is necessary for assessing the
severity of superior limbic keratoconjunctivitis (SLK). This study aimed to use a
novel quantitative marker to examine hyperemia in patients with SLK. MATERIALS
AND METHODS: We included six eyes of six patients with both dry eye disease and
SLK (SLK group) and eight eyes of eight patients with Sjogren syndrome (SS
group). We simultaneously obtained the objective finding scores by using slit
lamp examination and calculated the superior hyperemia index (SHI) with an
automated conjunctival hyperemia analysis software by using photographs of the
anterior segment. Three objective finding scores, including papillary formation
of the superior palpebral conjunctiva, superior limbal hyperemia and swelling,
and superior corneal epitheliopathy, were determined. The SHI was calculated as
the superior/temporal ratio of bulbar conjunctival hyperemia by using the
software. Fisher's exact test was used to compare a high SHI (>=1.07) ratio
between the SLK and SS groups. P-Values < 0.05 were considered statistically
significant. RESULTS: The SHI (mean +/- standard deviation) in the SLK and SS
groups was 1.19 +/- 0.50 and 0.69 +/- 0.24, respectively. The number of patients
with a high SHI (>=1.07) was significantly higher in the SLK group than in the SS
group (p < 0.05). The sensitivity and specificity of the SHI in the differential
diagnosis between SS and SLK were 66.7% and 87.5%, respectively. An analysis of
the association between the objective finding scores and SHI showed that the SHI
had a tendency to indicate the severity of superior limbal hyperemia and swelling
score in the SLK group. CONCLUSION: The SHI calculated using the automated
conjunctival hyperemia analysis software could successfully quantify superior
bulbar conjunctival hyperemia and may be a useful tool for the differential
diagnosis between SS and SLK and for the quantitative follow-up of patients with
SLK.
PMID- 29336628
TI - Effect of Multi-Ingredient Supplement Containing Satiereal, Naringin, and Vitamin
D on Body Composition, Mood, and Satiety in Overweight Adults.
AB - The purpose of this investigation was to examine the effects of 28 days of a
dietary supplement on body composition, mood, and satiety in overweight adults.
Twenty healthy adults (25.5 +/- 3.8 years; 87.3 +/- 20.7 kg; 169.9 +/- 10.6 cm;
29.9 +/- 5.1 body mass index) participated in this randomized, double-blind,
placebo-controlled investigation. Ten participants were provided with a dietary
supplement containing 178 mg satiereal, 100 mg naringin, and 2,000 IU vitamin D3
daily (SUPP), and ten participants were provided a placebo (PL) for 28 days.
Baseline (PRE) and post (POST) assessments included body mass, BMI, and waist
circumference measures. In addition, participants provided self-reported food
records and completed study questionnaires twice weekly. Questionnaires consisted
of profile of mood states, visual analog scales, modified trait food-cravings
questionnaire, and a modified state food-cravings questionnaire. No significant
differences were noted between groups for total calorie or macronutrient intake
(p = 0.65-0.92), body mass (p = 0.34), BMI (p = 0.24), or waist circumference
measures (p = 0.56-0.94). In addition, no significant differences between groups
were observed for mood states, subjective measures of food cravings, or feelings
of anxiety, fullness, bloating, hunger, craving, and stress (p >.05). In
conclusion, 28 days of a dietary supplement containing satiereal, naringin, and
vitamin D3 did not have any detectable beneficial effects on body-weight
management.
PMID- 29336629
TI - Pupillary manifestations of Marfan syndrome: from the Marfan eye consortium of
Chicago.
AB - BACKGROUND: Marfan syndrome (MFS) is a genetic disorder that affects multiple
organ systems, including the eye. The most common ocular manifestations include
ectopia lentis and retinal detachment. The current literature qualitatively cites
that MFS patients have miotic or "poorly dilating" pupils. This study was the
first to quantitatively assess pupillary function in MFS patients. MATERIALS AND
METHODS: 57 eyes from 29 MFS patients, 36 eyes from 18 pediatric age- and gender
matched controls, and 44 eyes from 22 adult age-matched controls were measured in
a clinic-based cross sectional study. Pupillometry data were measured in scotopic
conditions using the handheld NeurOptics PLR-200TM Pupillometer (NeurOptics,
Irvine, CA, USA). Data obtained with the pupillometer were maximum and minimum
diameter, constriction percentage, latency, average and maximum constriction
velocities, average dilation velocity, and 75% recovery time (T75). RESULTS:
Pediatric patients with MFS had significantly slower average constriction
velocity measurements (beta = 0.65, p = 0.0003), maximum constriction velocity
measurements (beta = 0.51, p = 0.0150) and average dilation velocity measurements
(beta = -0.19, p = 0.0029) compared to control patients. In the adult cohort,
results indicated significantly slower average dilation velocity measurements
(beta = -0.13, p = 0.0077) compared to controls. CONCLUSIONS: Our data highlight
pupillary parameters within a population of MFS patients under scotopic
conditions. Constriction and dilation velocities were slower in the pediatric MFS
patients compared to age- and gender-matched controls, and dilation velocities
were slower in the adult MFS patients compared to age-matched controls. These
findings, for the first time, quantitatively demonstrated differences in
pupillary function in patients with MFS.
PMID- 29336630
TI - Ameliorating Role of Lycopene, Tomato Puree, and Spirulina + Tomato Puree on the
Hematology of Fluoride-Exposed Swiss Albino Mice.
AB - Plant species rich in antioxidants (vitamins, flavonoids, lignans, and
carotenoids) have been explored for complementary therapy of chronic diseases
(cancers, coronary heart disease) and mitigation of pollutant toxicity. This
article investigates their ameliorative role on selective hematological and serum
biochemical parameters in fluoride-exposed (190 mg/kg body weight) Swiss albino
mice pretreated with the antioxidant-rich diet supplements tomato puree (with and
without peels), spirulina (cyanobacteria), and lycopene (present in tomato) for
45 days prior to entry into experimental protocol. Compared with standard feed
control, diet-modulated controls had more hairy and lustrous white fur,
hemodilution, increase in platelet counts (2- to 5-fold), red blood cell (RBC)
size (11%-14%), mean corpuscular hemoglobin (Hb) concentration (MCHC; 5%-14%),
and serum albumin (23%-27%). Fluoride-exposed mice reared on standard feed had
less hairy, pale white, lusterless fur and black nails, reduction in RBC and
white blood cell (WBC) counts and Hb content, and morphological abnormalities in
RBCs (poikilocytosis). By contrast, fur quality of fluoride-treated diet
modulated groups was similar to standard feed control; counts and morphology of
their RBCs and Hb content similar to the respective controls, and increase in WBC
counts greater than controls. In comparison to the fluoride-treated standard feed
group, platelet counts were higher in the treated mice of the diet-modulated
groups. This study thus revealed the hemoprotective role of diet supplements in
fluoride-treated mice. Considering the prevalence of fluoride-induced chronic
toxicity in developing countries, our findings have relevance in minimizing
hematological disorders among people residing in the fluoride-affected areas,
because indigenously cultivated low-price tomato fruits are easily available for
consumption.
PMID- 29336631
TI - The Beneficial Radioprotective Effect of Tomato Seed Oil Against Gamma Radiation
Induced Damage in Male Rats.
AB - Radiation protection research receives intense focus due to its significant
impact on human health. The present study was undertaken to investigate the
protective effect of pretreatment with tomato seed oil (TSO) against gamma
radiation-induced damage in rats. Male Wistar rats were divided into four groups:
(1) untreated control; (2) TSO-supplemented; (3) gamma-irradiated; (4) TSO
pretreated and gamma-irradiated. Acute exposure of animals to a single gamma
radiation dose (6 Gy) induced oxidative stress in major body organs, altered
serum lipid homeostasis, significantly increased serum testosterone and sorbitol
dehydrogenase levels, and elicited a systemic inflammation as manifested by the
induction of serum vascular cell adhesion molecule-1. Oral pretreatment with TSO
(1 ml/kg; 3 times/week for 8 weeks) before exposure to gamma radiation protected
rats against ionizing radiation-induced oxidative stress, restored lipid
homeostasis, and suppressed systemic inflammation. Histological findings of
target tissues verified biochemical data. The radioprotective ability of TSO was
attributed to its content of phytosterols, policosanol, and antioxidants,
including lycopene, beta-carotene, lutein, and tocopherols. TSO is considered a
promising radioprotective agent that can be effectively used to protect the body
from the damaging effects of harmful radiation.
PMID- 29336632
TI - Mobius syndrome with cardiac rhabdomyomas.
AB - BACKGROUND: Mobius syndrome is a rare congenital condition which presents not
merely with 6th and 7th nerve palsies, but involves gaze paresis associated with
craniofacial, limb, and other abnormalities. Heterogeneity is well known in
patients with Mobius syndrome and rather than being of familial inheritance based
on rare cases, it is much more recognized as a sporadic syndrome. We report an
infant with features of congenital Mobius syndrome associated with cardiac
rhabdomyomas in the absence of tuberous sclerosis. MATERIALS AND METHODS:
Observational case report of an infant seen at a tertiary academic center with
genetic testing, ophthalmic, neurological, and cardiac clinical examination and
imaging. RESULTS: A newborn baby boy at birth was seen with multiple congenital
craniofacial malformations, and respiratory distress. He was noted to have
micrognathia, retrognathia, wide nasal bridge, low set ears, high arched palate,
nonreducing bilateral talipes equinovarus and bilateral large angle esotropia
with -4 abduction deficit and facial palsy, findings suggestive of Mobius
Syndrome. MRI of the brain was unremarkable except for syringomyelia in the
cervical spine. Echocardiography showed two cardiac rhabdomyomas in the right
ventricle and ulltrasound of the abdomen showed mild right hydroneprosis.
Cytogenetics revealed segmental loss at 21q21.2. Testing for tuberous sclerosis
was negative for deletion or duplications of genes TSC1 and TSC2. CONCLUSION:
This case highlights the rare co-occurrence of cardiac rhabdomyomas with Mobius
syndrome and new segmental loss at 21q21.2 on genetic testing. Findings could
indicate not a "suggestion of Mobius", but rather the syndrome itself in
association with cardiac defects.
PMID- 29336633
TI - The relationship between asthma and depression in a community-based sample.
AB - OBJECTIVE: Asthma is an increasingly prevalent disease that is associated with
substantial physical and financial burdens. Additionally, asthma is linked to
psychiatric disorders. This study examines the relationship between asthma
diagnosis, current depressive symptoms, and lifetime psychiatric disorder history
in a large, community-based sample. METHODS: We analyzed data from 2168
participants in the Dallas Heart Study, a large, diverse, community-based sample
of people designed to be representative of the Dallas County population. Logistic
regressions analyzing the relationship between asthma diagnosis and history of a
psychiatric disorder, as well as between asthma diagnosis and the Quick Inventory
of Depressive Symptomatology (QIDS) scores were performed, controlling for
demographic data. RESULTS: 13.4% of the sample had an asthma diagnosis. Asthma
diagnosis was significantly associated with a history of nervous, emotional, or
mental health disorder diagnosis [OR 1.810 (95% CI 1.280-2.559) p = 0.001], and
with QIDS scores consistent with moderate or greater current depressive symptom
severity [OR 1.586 (95%CI 1.106-2.274) p = 0.012]. The relationships were not
moderated by age, gender, race, smoking status, or Body Mass Index. CONCLUSIONS:
A diagnosis of asthma may be associated with current clinically significant
levels of depressive symptoms and a lifetime psychiatric disorder. The current
report adds to the existing literature in this area by assessing both current and
lifetime symptoms and by using a large and diverse population. The findings
highlight the clinical importance of considering the possibility of psychiatric
illness in asthma patients and suggest further research in this area is needed.
PMID- 29336634
TI - sICAM-1, sVCAM-1 and sE-Selectin Levels in Type 1 Diabetes.
AB - BACKGROUND/OBJECTIVE: This study was performed to compare soluble levels of
adhesion molecules between diabetic patients and controls and to assess their
possible association with long-term complications of type 1 diabetes (T1D).
METHODS: Forty-eight patients with T1D and 39 healthy controls were enrolled in
this study. The plasma level of adhesion molecules was measured by sandwich
enzyme-linked immunosorbent assay technique. RESULTS: Higher sVCAM 1 (soluble
vascular cell adhesion molecule 1) levels correlated with older age of onset of
T1D. The plasma level of sICAM 1 (soluble intercellular adhesion molecule 1) was
significantly increased, while sE selectin was significantly decreased in
patients with T1D, compared to controls. There was no significant relationship
between these plasma-level variations and the long-term complications of T1D.
CONCLUSION: Although plasma levels of cell adhesion molecules are different in
T1D patients and healthy controls, they might not be good candidate markers for
prognosis of disease.
PMID- 29336635
TI - Lymphomatoid Granulomatosis in a 14-Year-Old Boy with Trisomy 21 and History of B
Lymphoblastic Leukemia/Lymphoma.
AB - BACKGROUND: Lymphomatoid granulomatosis is a EBV-driven lymphoproliferative
disorder that has been reported in association with immunodeficiency, but only
exceptionally in patients with hematopoietic malignancy. CASE REPORT: A 14-year
old boy with trisomy-21 and a history of B-lymphoblastic leukemia/lymphoma (B
ALL) diagnosed 1.5 years prior, on maintenance chemotherapy, presented with fever
and respiratory symptoms. Chest X-ray revealed right-lower-lobe consolidation. He
was treated for pneumonia but continued to be febrile with worsening respiratory
status, with development of additional pulmonary and liver nodules. No infectious
etiology was identified. Following nondiagnostic lung and liver biopsies, the
largest pulmonary mass was resected. The histopathologic findings were diagnostic
of lymphomatoid granulomatosis. There was no residual B-ALL. The patient's status
continued to deteriorate and he died shortly thereafter. CONCLUSION: Relative
immunosuppression due to maintenance therapy for B-ALL can lead to lymphomatoid
granulomatosis.
PMID- 29336636
TI - A Dysmorphology Based Systematic Approach Toward Perinatal Genetic Diagnosis in a
Fetal Autopsy Series.
AB - BACKGROUND: This retrospective study assesses the contribution of genetic
disorders in fetuses undergoing postmortem evaluation and the performance of a
clinical dysmorphology based systematic approach toward genetic diagnosis.
MATERIALS AND METHODS: Ninety fetuses, including spontaneous losses and
terminated pregnancies, underwent a postmortem evaluation including
dysmorphological examination, radiological studies, and histopathological
examination. Genetic testing including karyotyping, biochemical testing, Sanger
sequencing, and exome sequencing were performed selectively. RESULTS: A genetic
etiology was concluded in 48 fetuses (55%). As a standalone test,
dysmorphological examination was able to ascertain a definite genetic diagnosis
in sixteen cases, histopathology in six; and karyotyping, biochemical testing and
exome sequencing in two cases each (Total 28). Additionally, dysmorphology
findings indicated possible genetic disorder in 20 cases. CONCLUSION: Genetic
etiologies contribute significantly to fetuses undergoing autopsy in this series.
A systematic approach to postmortem fetal evaluation guided by dysmorphological
examination provides high diagnostic yield toward perinatal genetic diagnosis.
PMID- 29336637
TI - Post Mortem Diagnosis of Blake's Pouch Cyst: A Presentation of Distended Cyst at
Necropsy.
AB - BACKGROUND: Blake's pouch cyst forms from non-permeabilization of Blake's pouch.
It is difficult to visualize at necropsy as the cyst ruptures easily into the 4th
ventricle during dissection. CASE REPORT: Based upon prenatal imaging, delicate
dissection allowed post-mortem confirmation of the Blake's pouch cyst.
CONCLUSIONS: This highlights the importance of utilizing premortem imaging to
help guide the postmortem dissection and documentation of a posterior fossa cyst.
PMID- 29336638
TI - Prehospital Administration of Epinephrine in Pediatric Anaphylaxis - A Statewide
Perspective.
AB - OBJECTIVE: Timely administration of epinephrine is critical in the treatment of
anaphylaxis. This study sought to determine the frequency of administration of
epinephrine by EMS providers caring for pediatric patients in the prehospital
setting. METHODS: We examined data from the NC EMS database (PreMIS) from 2010-3
to determine frequency of epinephrine administration in pediatric patients with
anaphylaxis. We studied patients <18 years of age with an EMS provider impression
of "allergic reaction." Anaphylaxis was present if there was hypotension (defined
as SBP < 90 or DBP < 45 for patients age 11 and older, and SBP < 70 + (2 * age)
for patients ages 0-10), or impaired respirations (defined as description of
labored or absent respirations, or RR < 12 or > 30). We determined the overall
frequency of epinephrine administration. A multivariate logistic regression was
then constructed to examine the impact of the following variables on appropriate
epinephrine administration: age < 10, non-white race, rural county of case
origin, duration of transportation from scene, and presence of a paramedic.
RESULTS: A total of 504 patients met inclusion criteria, of which 471
demonstrated anaphylaxis as previously defined. A total of 153 patients with
anaphylaxis received epinephrine (32.4%, 95% CI 28.3-36.9%). Age < 10 was
associated with increased odds of not receiving epinephrine appropriately (OR
2.90, 95% CI 1.85-4.54, p < 0.001). Other variables did not have statistically
significant impact on epinephrine administration. CONCLUSION: There are missed
opportunities for prehospital administration of epinephrine in pediatric patients
with anaphylaxis. Very young children (age < 10) had increased odds for not
receiving epinephrine.
PMID- 29336639
TI - Intellectual, educational, and situation-based social outcome in adult survivors
of childhood medulloblastoma.
AB - PURPOSE: To investigate intellectual and situation-based social outcome and
educational achievement in adult survivors of childhood medulloblastoma and
analyse factors influencing outcome Methods: We collected demographic, medical
and cognitive data, and social and educational outcome at a mean time since the
end of treatments of 14.9 years in 58 adults, aged 19-35 years, consecutively
treated in a single cancer center between 1989 and 2005. RESULTS: Ten survivors
had severe intellectual disability, 12 were still studying, 23 had a regular
employment and 13 were unemployed. Full Scale Intellectual Quotient, assessed 6.6
years after the end of treatments, ranged from 46 to 131. It was strongly
associated with educational achievement and significantly lower in patients who
experienced postoperative cerebellar mutism, and when parental education level
was low. CONCLUSION: These factors should be systematically considered at
diagnosis in order to offer adequate and timely assessments and interventions.
PMID- 29336640
TI - Novel RNASET2 Pathogenic Variants in an East Asian Child with Delayed Psychomotor
Development.
AB - INTRODUCTION: RNASET2 mutation has been reported in patients with cystic
leukoencephalopathy without megalencephaly and the Aicardi-Goutieres syndrome.
Both disorders are Mendelian mimics of congenital cytomegalovirus infection with
overlapping features, including leukoencephalopathy, white matter alterations,
intracranial calcification, delayed psychomotor development, intelligence
disability and seizures. Only eight families with RNASET2 mutation have been
previously reported. METHODS: Whole exome sequencing was performed and copy
number variants were described by read-depth strategy. RESULTS: We identified a
novel nonsense variant c.128G>A (p. W43*) and a 430 Kb 6q27 microdeletion
encompassing RNASET2. Our patient did not show anterior temporal lobe subcortical
cysts, hearing loss, dystonia or extra-neurological features. CONCLUSION: Our
results provided further genetic and phenotypic information of RNASET2 mutation
in Chinese patients and highlighted the importance for physicians to consider
RNASET2-related disorders when diagnosing patients with congenital brain
infection-like phenotypes.
PMID- 29336641
TI - Impact of Forward and Backward Scattering and Corneal Higher-Order Aberrations on
Visual Acuity after Penetrating Keratoplasty.
AB - PURPOSE: To assess the relationship of forward and backward scattering and
corneal higher-order aberrations (HOAs) with corrected distance visual acuity
(CDVA) after penetrating keratoplasty (PK). METHODS: This retrospective study
comprised 25 eyes of 25 consecutive patients who underwent PK using the VisuMax
femtosecond laser system and age-matched 25 eyes of 25 healthy subjects. We
quantitatively assessed objective scattering index (OSI) using the double-pass
instrument (OQAS II, Visiometrics), corneal densitometry (CD) and corneal HOAs
with the Scheimpflug rotating camera (Pentacam HR, Oculus) 1 year
postoperatively. RESULTS: The OSI, CD, and corneal HOAs were significantly larger
in the PK group than those in the control group (p <= 0.011). We found
significant correlations of logMAR CDVA with the OSI (r = 0.477, p = 0.016), and
with the anterior, posterior, and total corneal HOAs of the central 4-mm zone
(anterior: r = 0.573, p = 0.003, posterior: r = 0.596, p = 0.002, total: r =
0.472, p = 0.017), but no significant association with the CD of the 0-2 mm zone
at any layers (anterior: r = 0.236, p = 0.257, center: r = 0.139, p = 0.506,
posterior: r = 0.073, p = 0.728, total: r = 0.212, p = 0.308). Similar results
were obtained when the analysis was repeated with corneal HOAs of the central 6
mm zone and CDs in 2-6 mm zone. CONCLUSIONS: Our pilot study demonstrated that
the postoperative CDVA was significantly correlated with OSI and corneal HOAs,
but not with backward scattering in post-PK eyes, suggesting that OSI as well as
corneal HOAs plays an essential role in postoperative visual performance after
PK.
PMID- 29336642
TI - Concurrent Validity of Two Gait Performance Measures in Children with Neuromotor
Disorders.
AB - AIMS: To investigate the concurrent validity of two mobility performance
measures, the Functional Mobility Scale (FMS) and the Gillette Functional
Assessment Questionnaire - walking scale (FAQ) in an inpatient pediatric
neurorehabilitation setting. METHODS: Cross-sectional data were collected on 71
children (mean age 12.7 years) with neuromotor gait impairments who participated
in an inpatient rehabilitation program to evaluate aspects of concurrent validity
of the FMS and FAQ. Physiotherapists independently performed ratings. Comparator
instruments included the walking item of the Functional Independence Measure for
children, 10-m and 6-minute walking tests, and Gross Motor Function Measure-88
dimension E. All tests were completed within 7 days. Spearman correlation
coefficients were calculated to test a priori formulated hypotheses regarding the
strength and direction of the measures relationships. RESULTS: The children had a
broad spectrum of mobility levels, including all levels of FMS and levels 2-10 of
FAQ. Spearman correlation coefficients with comparator measures varied between
0.58-0.79 for the FMS and 0.69-0.73 for the FAQ. Hypotheses concerning
correlation strengths and directions were met for FMS and FAQ. CONCLUSIONS: The
findings demonstrate that the FMS and FAQ are valid to evaluate functional
mobility in pediatric inpatient neurorehabilitation.
PMID- 29336643
TI - Measurement of Fetal Mesencephalon and Pons Via Ultrasonographic Cross Sectional
Imagining.
AB - OBJECTIVES: This study evaluated the feasibility of measuring the fetal
mesencephalon and pons by ultrasonographic cross sectional imaging to detect
fetal central nervous system developmental abnormalities. MATERIALS AND METHODS:
Fetal ultrasonographic measurements included: Fetal mesencephalon anteroposterior
diameters (MAD), mesencephalon transverse diameters (MTD), pons anteroposterior
diameter (PAD) and proximal transverse diameters (PTD). RESULTS: Nine-hundred
ninety fetuses were imaged. Thirty-eight fetuses (observation group) presented
central nervous system abnormalities; 952 fetuses without imaged abnormalities
were utilized as the reference (control) group. Fetal MAD, MTD, PAD, and PTD in
control fetuses showed a linear correlation with gestational age. Thirty-eight
fetuses had 40 abnormal measurements (8 MAD, 8 MTD, 14 PAD, and 10 PTD), 16 in
mesencephalon, and 24 in pons. All data fell below the 95% confidence intervals'
lower limits for the corresponding gestational age. CONCLUSION: Using normative
data based on 957 fetuses allows detection of size abnormalities of the pons and
midbrain during fetal life.
PMID- 29336644
TI - Evidence, education and multi-disciplinary integration are needed to embed
exercise into lung cancer clinical care: A qualitative study involving
physiotherapists.
AB - AIMS: To explore physiotherapists perceptions regarding barriers and enablers to
embedding exercise into routine lung cancer clinical care. DESIGN: Qualitative
study (content analysis). Eight physiotherapists working in the area of lung
cancer at five hospitals participated. The focus group was conducted, transcribed
verbatim and independently crosschecked. Thematic analysis was utilized. RESULTS:
The data generated four major themes: evidence justifying exercise; staffing and
services; maximising the efficacy of interventions; and hospital culture.
Physiotherapists perceived that barriers included lack of evidence, lack of
physiotherapy time and funding, inconsistencies in patient access to outpatient
exercise programs, lack of clear referral pathways, limited knowledge about
exercise by the wider multi-disciplinary team, and poor culture of physical
activity in the inpatient setting. Recommendations included developing a stronger
evidence-base, establishing set patient pathways into exercise programs, re
allocating physiotherapy services to high-risk patients, and
integrating/involving the multi-disciplinary team particularly through education
and communication. CONCLUSION: This study has identified barriers to, and
potential strategies for, the embedding of exercise into lung cancer clinical
practice. Evidence, education and multi-disciplinary integration are viewed by
physiotherapists as critical for success. A targeted gradual approach, by
applying these strategies at defined stages across the lung cancer pathway, is
recommended to facilitate future practice change.
PMID- 29336645
TI - Physical exercise prior to hematopoietic stem cell transplantation: A feasibility
study.
AB - PURPOSE: This study explores the feasibility and preliminary effectiveness of an
exercise program in people scheduled for hematopoietic stem cell transplantation
(HSCT). METHODS: In this controlled clinical trial, we compare pre
transplantation exercise to no exercise in the waiting period for an allogeneic
of autologous HSCT. The supervised individually tailored exercise program (4-6
weeks) consisted of aerobic endurance, muscle strength, and relaxation exercises,
administered twice a week in the period prior to HSCT. Feasibility was determined
based on inclusion rate, attrition rate, adherence to intervention, safety, and
satisfaction (0-10). Preliminary effectiveness was determined primarily by self
perceived physical functioning, quality of life (QOL), and fatigue. Secondary
outcomes were global perceived effect (GPE), blood counts, hospital stay, and
physical fitness. RESULTS: Forty-six patients were eligible, of whom 29 (69%)
participated: 14 in the intervention group and 15 in the control group. The
adherence rate to training was 69%. No adverse events or injuries occurred.
Satisfaction of training conditions was high (mean 9.2 +/- 1.3). Positive (follow
up) trends in favor of the intervention group were found for self-perceived
physical functioning, QOL, fatigue, GPE, blood counts, and hospital stay.
CONCLUSION: Exercise prior to HSCT is safe and feasible, and positive trends
suggest favorable preliminary effectiveness. Adherence to the exercise program
needs to be optimized in a future trial.
PMID- 29336646
TI - Anti-cyclic citrullinated peptide antibodies, other common autoantibodies, and
smoking as risk factors for lymphoma in patients with rheumatoid arthritis.
AB - OBJECTIVES: Patients with rheumatoid arthritis (RA) are at increased risk of
lymphoma. There is no biomarker to indicate future lymphoma risk in RA and it is
not known whether factors associated with an increased risk of RA also confer an
increased risk of lymphoma. We investigated whether anti-cyclic citrullinated
peptide (CCP) antibodies, other autoantibodies, and smoking, are associated with
lymphoma development in RA. METHOD: From two population-based case-control
studies, the Scandinavian Lymphoma Etiology (SCALE) study and the Epidemiological
Investigation of Rheumatoid Arthritis (EIRA) I study, we identified lymphoma
cases with a validated RA diagnosis (n = 50), to whom we matched study
participants with RA but no lymphoma (n = 261), lymphoma but no RA (n = 257), and
neither RA nor lymphoma (n = 233). Lymphomas were classified according to the WHO
classification. Blood samples were analysed for immunoglobulin G (IgG), IgM, and
IgA isotypes and IgG1-4 subclasses of anti-CCP antibodies and for 15 antinuclear
antibody (ANA)-associated specific autoantibodies. Relative risks were estimated
as crude and adjusted odds ratios (adjOR) with 95% confidence intervals (CIs)
using logistic regression. RESULTS: We found no association between anti-CCP IgG
>= 25 units/mL (adjOR 1.4, 95% CI 0.7-2.7), anti-CCP IgG >= 500 units/mL (adjOR
1.4, 95% CI 0.7-3.0), anti-CCP Ig of other isotypes, other autoantibodies (adjOR
any vs none 0.6, 95% CI 0.3-1.2), or cigarette smoking (adjOR ever vs never 1.1,
95% CI 0.5-2.2) and lymphoma risk among patients with RA. CONCLUSION: In this
study, neither anti-CCP antibodies (IgG, IgG1-4, IgM, or IgA), nor other common
autoantibodies, nor smoking predicted lymphoma risk in RA.
PMID- 29336647
TI - Inflammatory Myofibroblastic Tumor of the Tongue. Report of a Pediatric Case and
Review of the Literature.
AB - BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is an uncommon mesenchymal
lesion composed of myofibroblastic and fibroblastic spindle cells, accompanied by
inflammatory infiltration. IMT may occur in the tongue. Five cases have been
previously reported at this site. CASE REPORT: An inflammatory myofibroblastic
tumor arose in the tongue of a 10 month old infant, confirmed by anaplastic
lymphoma kinase (ALK) immunohistochemical staining and the clinical response to
the tyrosine kinase inhibitor. CONCLUSIONS: IMT can occur in the tongue. This
report highlights the differential diagnosis of IMT. ALK staining is both a
helpful diagnostic marker and a predictive marker for targeted therapy in this
tumor type.
PMID- 29336648
TI - Rhythmic arm swing integrated into treadmill training in patients with chronic
stroke: A single-subject experimental study.
AB - Normal walking includes coordinated and controlled movement of the legs and arms.
However, patients following stroke often present with inappropriate motor control
which limits coordinated movement patterns of the affected limbs. This study
aimed to compare the effects of rhythmic arm swing and arm fixation during
treadmill walking in patients with poststroke hemiparesis. We used an alternating
study design with multiple baselines across subjects. Three patients with chronic
stroke participated in this study. During treadmill walking, rhythmic arm swing
and arm fixation conditions were alternately applied. Outcome measures included
the 10-meter walk test (10MWT) and energy expenditure index (EEI). In the
intervention phase, all subjects showed significantly greater improvements in the
10MWT and EEI scores for rhythmic arm swing condition compared to those for arm
fixation condition (p < 0.05). 10MWT improvement rates: Subject 1-34.81% vs.
15.75%; Subject 2-40.00% vs. 17.95%; and Subject 3-38.08% vs. 21.85%; and EEI
improvements: Subject 1-23.19% vs. 14.08%; Subject 2-26.15% vs. 20.43%; and
Subject 3-22.99% vs. 14.49%. These findings suggest that rhythmic arm swing is
clinically feasible as a more favorable option to enhance the effects of
treadmill walking training. However, larger studies with a different study design
are needed to be able to make any judgment about the usefulness of the treatment.
PMID- 29336649
TI - Severe Craniofacial Involvement due to Amniotic Band Sequence.
AB - BACKGROUND: Disruptive amniotic band sequence (DABS) is a sporadic, non-familial
disorder with unclear etiology. Diagnosis is based on clinical features because
there is currently no reliable laboratory diagnostic tests. OBJECTIVE: We
describe six cases of DABS with severe craniofacial deformations, three with and
three without classical constrictive limb deformation. RESULTS: The craniofacial
deformities were delimited by peripheral sharply demarcated scarring. CONCLUSION:
When a sharply demarcated linear disruptive craniofacial lesion is observed, DABS
should be considered despite the absence of constrictive limb scarring.
PMID- 29336650
TI - Association of REL Polymorphism with Cow's Milk Proteins Allergy in Pediatric
Algerian Population.
AB - INTRODUCTION: Cow's milk proteins allergy (CMPA) pathogenesis involves complex
immunological mechanisms with the participation of several cells and molecules
involved in food allergy. The association of polymorphisms in the interleukin 4,
Forkhead box P3 and the avian reticuloendotheliosis genes was investigated in an
infant population with CMPA of Western Algeria. MATERIALS AND METHODS: We
obtained DNA and clinical data from milk allergic subjects during active phase
and from a group of non-atopic control subjects. RESULTS: Our findings showed
that the allele G of the cRel gene intronic polymorphism at +7883 positions was
significantly higher among cow's milk proteins allergic patients compared to
control subjects. CONCLUSION: The results of this study suggest a possible
association of CMPA with cRel G+7883T polymorphism.
PMID- 29336651
TI - Formal and Informal Control of Cannabis: Regular Users' Experience.
AB - BACKGROUND: The debate on recreational use of cannabis, recently relaunched by
the election of the Liberal Party of Canada that intends to legalize and regulate
its use and access, implies a better understanding of social control mechanisms
that are in place, and their influence on users' behaviors. OBJECTIVE: This study
addresses the issue of formal and informal controls by providing, first, a
theoretical perspective of this concept, and, second, by illustrating its
operation from the users' perspective. METHODS: Semi-structured interviews were
conducted with 164 regular, adult cannabis users recruited in four large Canadian
cities (Vancouver, Toronto, Montreal, and Halifax). An initial qualitative
analysis based on the principles of grounded theory was conducted. The main
categories identified were then used to find and re-code relevant material on the
respondents' experience with formal and informal control (secondary analysis).
RESULTS: The users' perspective shows that mechanisms of informal control play an
important role in defining the social context of their use (when, where, and with
whom cannabis is consumed). In contrast, formal control had no deterrent impact
on the cessation or reduction of use, but affected their behavior by influencing
them to change the context of their practices to avoid criminal legal
consequences and stigmatization. Conclusions/Importance: The regulatory controls
based in public health that the Canadian government plans to implement (replacing
criminal ones), should be based on a better understanding of current practices
and patterns of cannabis users, and in accordance with informal controls already
in place. Legislative formal controls, in a regulatory model, that are better
defined and consistent with social practices, will be more accepted and respected
by the user population and thus likely to be more effective in reducing harm.
PMID- 29336652
TI - Detection of STEMI Using Prehospital Serial 12-Lead Electrocardiograms.
AB - OBJECTIVE: Repeated or serial 12-lead electrocardiograms (ECGs) in the
prehospital setting may improve management of patients with subtle ST-segment
elevation (STE) or with a ST-segment elevation myocardial infarction (STEMI) that
evolves over time. However, there is a minimal amount of scientific evidence
available to support the clinical utility of this method. Our objective was to
evaluate the use of serial 12-lead ECGs to detect STEMI in patients during
transport in a Canadian emergency medical services (EMS) jurisdiction. METHODS:
We performed a retrospective study of suspected STEMI patients transported by EMS
in the Chaudiere-Appalaches region (Quebec, Canada) between August 2006 and
December 2013. Patients were monitored by a serial 12-lead ECG system where an
averaged ECG was transmitted every 2 minutes. Following review by an emergency
physician, ECGs were grouped as having either a persistent STE or a dynamic STE
that evolved over time. RESULTS: A total of 754 suspected STEMI patients were
transported by EMS during the study period. Of these, 728 patients met
eligibility criteria and were included in the analysis. A persistent STE was
observed in 84.3% (614/728) of patients, while the remaining 15.7% (114/728) had
a dynamic STE. Among those with dynamic STE, 11.1% (81/728) had 1 ST-segment
change (41 no-STEMI to STEMI; 40 STEMI to no-STEMI) and 4.5% (33/728) had >= 2 ST
segment changes (17 no-STEMI to STEMI; 16 STEMI to no-STEMI). Overall, in 8.0%
(58/728) of the cohort, STEMI was identified on a subsequent ECG following an
initial no-STEMI ECG. CONCLUSIONS: Through recognition of transient ST-segment
changes during transport via the prehospital serial 12-lead ECG system, STEMI was
identified in 8% of suspected STEMI patients who had an initial no-STEMI ECG. Key
words: electrocardiography; emergency medical services; ST-elevation myocardial
infarction; prehospital dynamic ECG.
PMID- 29336653
TI - Assessment of spatial heterogeneity in continuous twin screw wet granulation
process using three-compartmental population balance model.
AB - In this study, a novel three-compartmental population balance model (PBM) for a
continuous twin screw wet granulation process is developed, combining the
techniques of PBM and regression process modeling. The developed model links
screw configuration, screw speed, and blend throughput with granule properties to
predict the granule size distribution (GSD) and volume-average granule diameter.
The granulator screw barrel was divided into three compartments along barrel
length: wetting compartment, mixing compartment, and steady growth compartment.
Different granulation mechanisms are assumed in each compartment. The proposed
model therefore considers spatial heterogeneity, improving model prediction
accuracy. An industrial data set containing 14 experiments is applied for model
development. Three validation experiments show that the three-compartmental PBM
can accurately predict granule diameter and size distribution at randomly
selected operating conditions. Sixteen combinations of aggregation and breakage
kernels are investigated in predicting the experimental GSD to best judge the
granulation mechanism. The three-compartmental model is compared with a one
compartmental model in predicting granule diameter at different experimental
conditions to demonstrate its advantage. The influence of the screw
configuration, screw speed and blend throughput on the volume-average granule
diameter is analyzed based on the developed model.
PMID- 29336654
TI - Serotonin Syndrome in Tapentadol Literature: Systematic Review of Original
Research.
AB - The potential association between serotonin syndrome and tapentadol is not well
described in the literature. This study aimed to review the literature and
identify methodological issues that could lead to inaccurately reported rates of
serotonin syndrome associated with tapentadol use. A systematic review of English
articles using MEDLINE, Cochrane Controlled Trials Register, and Scopus was
performed. Additional studies were identified by cross-referencing article
bibliographies. Original research that examined the safety of tapentadol in
patients with nonconfounding indications were examined. In total, 22 studies met
inclusion criteria. There were 13 randomized clinical trials, 7 open-label
trials, and 2 observational studies. All studies either did not mention whether
serotonergic medication use was prohibited or disallowed use. Frequently reported
adverse events were nausea, diarrhea, constipation, fatigue, vomiting, and
somnolence. No studies reported serotonin syndrome development. No included
trials differentiated between the development of adverse events in patients
taking serotonergic drugs and those who were not. This differentiation is
necessary to evaluate the increased risk of adverse events in patients prescribed
tapentadol concomitantly with other serotonergic medications. Therefore, the
current tapentadol literature has important limitations that prevent the adequate
characterization of the potential association between tapentadol and serotonin
syndrome.
PMID- 29336655
TI - Reversible cicatricial ectropion associated with EGFR inhibitors.
AB - The management of cicatricial ectropion resulting from epidermal growth factor
receptor (EGFR) inhibitors is unclear. We describe two cases of bilateral
cicatricial ectropion following the use of an EGFR inhibitor who were treated
with oral doxycycline, topical ophthalmic steroid and antibiotic ointment to the
eyelids, and topical facial steroid cream with lubrication. The first case
resolved with discontinuation of panitumumab infusions along with institution of
the aforementioned regimen. However, it is unclear whether the resolution was
from discontinuation of the infusions or from the instituted regimen. The second
case resolved without a dose adjustment of cituximab. This case may provide
support for the use of this regimen prior to discontinuation of the offending
agent, as there was a successful outcome without alteration of the infusions.
Additional cases are necessary to determine if this is a successful means of
treating bilateral lower-lid cicatricial ectropion from EGFR inhibitors.
PMID- 29336656
TI - The use of mastoid vibration with canalith repositioning procedure to treat
persistent benign paroxysmal positional vertigo: A case report.
AB - The Canalith Repositioning Procedure (CRP) was originally described as a non
invasive treatment for Benign Paroxysmal Positional Vertigo (BPPV) by Epley.
Since its inception, the maneuver has undergone several modifications; and
currently is performed in the absence of induced mastoid vibration (oscillation).
Clinically, mastoid vibration may be used to assist in treatment of persistent
cases of BPPV, where a simple CRP may fail to improve symptoms. This case
describes a patient with a three-month history of BPPV (right posterior
canalithiasis), who was previously treated unsuccessfully with standard CRP.
Mastoid vibration was introduced as part of the treatment due to persistent BPPV.
After one treatment utilizing CRP with mastoid vibration, the patient had
complete resolution of symptoms, and remained symptom free at a six-month follow
up. It can be concluded that introducing mastoid oscillation via vibration to the
CRP in persistent cases of semicircular canalithiasis BPPV may produce positive
patient outcomes.
PMID- 29336657
TI - What Factors are Associated with Electronic Cigarette, Shisha-Tobacco and
Conventional Cigarette Use? Findings from a Cross-Sectional Survey of Australian
Adolescents?
AB - BACKGROUND: Adolescents' use of electronic cigarettes and shisha-tobacco
increased in several countries during the 2000s, including in the United States,
United Kingdom and Canada. Few studies have examined the factors associated with
exclusive e-cigarette or shisha-tobacco use and whether adolescents using these
substances exclusively differ from those using traditional cigarettes.
OBJECTIVES: To examine the socio-demographic and behavioural correlates of
exclusive e-cigarette and exclusive shisha-tobacco use to those found for users
of tobacco cigarettes and multiple nicotine products in Australian adolescents.
METHODS: Cross-sectional survey of smoking behaviours of a random sample of 4,576
students in the Australian state of Victoria aged 12-17 conducted between June
2014 and December 2014. RESULTS: Overall, 14% of students had used an e-cigarette
with 3% using e-cigarettes exclusively. 13% had used shisha-tobacco, with 2%
using shisha-tobacco exclusively. Most students (65%) using e-cigarette and
shisha-tobacco (67%) had also used tobacco cigarettes. After adjusting for
demographic factors, students using e-cigarettes only were more likely to have
never used cannabis or drink alcohol in the past year compared to tobacco
cigarette users. Compared to tobacco cigarette users, students using only shisha
tobacco were younger, less likely to use cannabis or alcohol or have friends or
parents who smoke. CONCLUSIONS: Most Australian adolescents who use alternative
nicotine and tobacco-related products do so in conjunction with tobacco
cigarettes. Students using e-cigarettes or shisha-tobacco exclusively were less
likely to use other substances. Australian longitudinal studies are needed to
determine whether this group of students are on a pathway to traditional tobacco
use.
PMID- 29336658
TI - Just a First-Year Thing? The Relations between Drinking During Orientation Week
and Subsequent Academic Year Drinking Across Class Years.
AB - BACKGROUND: The goal of Orientation Week is to help new students adjust to
university life. However, it is a period when many new students engage in
excessive alcohol consumption and where problematic drinking patterns may be
established. OBJECTIVE: The objective is to determine whether returning students
drink in a similar manner to students in their first-year of classes and whether
Orientation Week drinking predicts semester drinking more strongly for first-year
than returning students. METHODS: We tested 552 students (18 to 25 years old) in
their first, second, or third class year of university. Students reported their
Orientation Week drinking and then completed daily drinking diaries for 13
consecutive days during the academic year. RESULTS: Orientation Week drinking was
similar across class years and also predicted academic year drinking for students
in all class years. Conclusion/Importance: Drinking during Orientation Week is
not just a first-year problem and prevention efforts should focus on all
students.
PMID- 29336659
TI - Long non-coding RNA HOTAIR promotes cervical cancer progression through
regulating BCL2 via targeting miR-143-3p.
AB - BACKGROUND: HOX transcript antisense RNA (HOTAIR) is a long non-coding RNA
(lncRNA) widely involved in the progression of numerous malignancies. Whereas,
the potential molecular mechanism of HOTAIR involved in cervical cancer
progression is still needed to be elaborated. METHODS: The expression of HOTAIR
and miR-143-3p were detected in cervical cancer tissues and cells by qRT-PCR. MTT
and flow cytometry analysis were performed to measure cell proliferation and
apoptosis. Bioinformatics, Dual-Luciferase reporter and RIP were used to analyze
the possible correlation between HOTAIR, miR-143-3p and BCL2. The expression of
Bax and BCL2 was detected by western blot. Mice xenograft model was established
to confirm the role of HOTAIR on tumor growth in vivo. RESULTS: HOTAIR expression
was elevated while miR-143-3p expression was reduced in cervical cancer tissues
and cell lines. HOTAIR knockdown suppressed proliferation and enhanced apoptosis
in cervical cancer cells. Moreover, HOTAIR could function as a sponge for miR-143
3p. The inhibitory effect of HOTAIR knockdown on cervical cancer cells growth was
abolished following decrease of miR-143-3p expression. Furthermore, HOTAIR
promoted BCL2 expression by modulating miR-143-3p. BCL2 overexpression attenuated
the tumor-suppressive effect of miR-143-3p in cervical cancer. Finally, the
carcinogenicity of HOTAIR was validated in mice. CONCLUSIONS: HOTAIR promoted
cervical cancer cell growth by modulating BCL2 via miR-143-3p, hinting a novel
regulatory mechanism and potential therapeutic target in cervical cancer.
PMID- 29336660
TI - Current Practice Patterns Surrounding Fertility Concerns in Stage I Seminoma
Patients: Survey of United States Radiation Oncologists.
AB - PURPOSE: Patients with testicular seminoma may face fertility issues because of
their underlying disease as well as treatments they undergo. The current patterns
of practice among U.S. radiation oncologists aimed at assessing and preserving
fertility in patients with Stage I seminoma are unknown. METHODS: We surveyed
practicing U.S. radiation oncologists via an Institutional Review Board-approved
online questionnaire. Respondents' characteristics and perceived patient
infertility rates were analyzed for association with treatment recommendations.
RESULTS: We received 353 responses, of whom one quarter (23%) consider themselves
experts. A vast majority (84%) recommend observation as a default strategy. Fifty
two percent routinely advise fertility assessment for patients before observation
or chemotherapy, and 74% routinely do so before adjuvant radiation therapy (RT).
Forty-one percent and 43% believe that 10% and 30% of patients are infertile
following orchiectomy, respectively. Thirty-seven percent and 22% believe
infertility rates following para-aortic RT to be 30% and 50%, respectively.
Eighty percent routinely use clamshell scrotal shielding. Responders with higher
perceived infertility rates are more likely to recommend fertility
assessment/sperm banking (Fisher's exact p < 0.0001). Responders who routinely
advised fertility assessment were more likely to use clamshell shielding (Cochran
Armitage trend test p = 0.0007). Clamshell use was positively correlated with
higher perceived infertility rates following para-aortic RT (Spearman's
correlation coefficient = 0.006). CONCLUSIONS: Despite a clear knowledge of
fertility issues in men diagnosed with seminoma, there is no universal adoption
of fertility assessment among U.S. radiation oncologists.
PMID- 29336661
TI - Cancer-Related Genetic Testing and Personalized Medicine for Adolescents: A
Narrative Review of Impact and Understanding.
AB - Genetic testing is becoming increasingly available for adolescents who are
undergoing cancer treatment or at risk of cancer predisposition syndromes. With
this narrative review, we aimed to synthesize the evidence on psychosocial
outcomes and adolescents' understanding of genetic testing-thus far, an
underresearched topic. Both psychological benefits and harms of predictive
testing were reported in adolescents from high-risk families. Harms were mainly
related to cancer-specific distress and increased worries. Findings on genetic
understanding were sparse. Future studies should focus on psychosocial outcomes
and adolescents' understanding undergoing genetic testing and enabling access to
genetic counseling pre-testing and post-testing.
PMID- 29336663
TI - Lactobacillus acidophilus Improves Intestinal Inflammation in an Acute Colitis
Mouse Model by Regulation of Th17 and Treg Cell Balance and Fibrosis Development.
AB - Disruption of the balance among the microbiota, epithelial cells, and resident
immune cells in the intestine is involved in the pathogenesis of inflammatory
bowel disease (IBD). Probiotics exert protective effects against IBD, and
probiotic commensal Lactobacillus species are common inhabitants of the natural
microbiota, especially in the gut. To investigate the effects of Lactobacillus
acidophilus on the development of IBD, L. acidophilus was administered orally in
mice with dextran sodium sulfate (DSS)-induced colitis. DSS-induced damage and
the therapeutic effect of L. acidophilus were investigated. Treatment with L.
acidophilus attenuated the severity of DSS-induced colitis. Specifically, it
suppressed proinflammatory cytokines such as interleukin (IL)-6, tumor necrosis
factor-alpha, IL-1beta, and IL-17 in the colon tissues, which are produced by T
helper (Th) 17 cells. Moreover, in vitro L. acidophilus treatment directly
induced T regulatory (Treg) cells and the production of IL-10, whereas the
production of IL-17 was suppressed in splenocytes. In addition, we found that L.
acidophilus treatment decreased the levels of alpha-smooth muscle actin, a marker
of activated myofibroblasts, and type I collagen compared with control mice.
These results suggest that L. acidophilus may be a novel treatment for IBD by
modulating the balance between Th17 and Treg cells, as well as fibrosis
development.
PMID- 29336662
TI - Body mass index in HER2-negative metastatic breast cancer treated with first-line
paclitaxel and bevacizumab.
AB - The evidence emerged from the TOURANDOT trial encourages evaluating the role of
anthropometric determinants on treatment outcomes in HER2-negative metastatic
breast cancer patients treated with bevacizumab-including regimens. We thus
analyzed data from a subgroup of these patients from a larger cohort previously
assessed for treatment outcomes. Patients were included in the present analysis
if body mass index values had been recorded at baseline. Clinical benefit rates,
progression free survival and overall survival were assessed for the overall
study population and subgroups defined upon molecular subtype. One hundred ninety
six patients were included (N:196). Body mass index showed no impact on clinical
benefit rates in the overall study sample and in the luminal cancer subset (p =
0.12 and p = 0.79, respectively), but did so in the triple negative subgroup,
with higher rates in patients with body mass index >=25 (p = 0.03). In the
overall study sample, body mass index did no impact progression free or overall
survival (p = 0.33 and p = 0.67, respectively). Conversely, in triple negative
patients, progression free survival was significantly longer with body mass index
>=25 (6 vs 14 months, p = 0.04). In this subset, overall survival was more
favorable (25 vs 19 months, p = 0.02). The impact of the molecular subtype was
confirmed in multivariate models including the length of progression free
survival, and number of metastatic sites (p < 0.0001). Further studies are
warranted to confirm our findings in more adequately sized, ad hoc, prospective
studies.
PMID- 29336664
TI - Grab and passive sampling applied to pesticide analysis in the Sao Lourenco river
headwater in Campo Verde - MT, Brazil.
AB - In this study, the quality of surface water in the headwaters of Sao Lourenco
River in Mato Grosso, Brazil, was evaluated in relation to contamination by
pesticides. For this purpose, samples were collected between December 2015 and
June 2016 by grab sampling and by passive sampling using an integrative polar
organic compound sampler installed in the field during four 14-day cycles between
March and June 2016. The analyses were performed by gas chromatography (CG/MS)
and by liquid chromatography (UPLC-MS/MS). The results showed the detection of
two pesticides (atrazine and pyraclostrobin) of the five analyzed by passive
sampling and eight active principles among the 20 analyzed (malathion, diuron,
carbofuran, carbendazim, trifluralin, imidacloprid, metolachlor, and acetamiprid)
by grab sampling. The detection of 10 pesticides, even almost a decade after the
beginning of a recovery process of the ciliary forest, confirms the headwaters'
vulnerability to these contaminants and passive sampling proved to be an
important tool in capturing small concentrations of pesticides constituting an
interesting complement to grab sampling.
PMID- 29336665
TI - Pesticide exposure and health conditions among orange growers in Southern Brazil.
AB - This study aimed to evaluate the exposure to pesticides through the biomarkers
analysis, as well as life habits and use of Personal Protective Equipment (PPE)
in a group of farmers who grow citrus in the Vale do Cai region, in Rio Grande do
Sul, southern Brazil. The study population consisted of 73 volunteer farmers, 45
males and 28 females, aged between 13 and 69 years old. The control group
consisted of 30 individuals who were not exposed to pesticides. Measures of urea,
creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT),
gamma-glutamyltransferase (GGT), plasma cholinesterase (BChE) activity, and
hematological parameters were analyzed. The study population also answered a
structured questionnaire on life habits and health. The results showed that BChE
activity was significantly lower in the exposed group than in the control group.
AST, ALT, and creatinine were increased in the group of women exposed to
pesticides when compared to the control group. GGT, urea, and hematological
parameters did not show statistical differences for both male and female group.
The most prevalent symptom reported by farmers after exposure to pesticides was
headache. Furthermore, it was verified that the use of complete PPE is only made
by 38% of the studied population.
PMID- 29336666
TI - Educational Needs of Health Professionals Caring for Adolescents and Young Adults
with Cancer.
AB - BACKGROUND: Young people with cancer have distinct clinical and psychosocial
needs during and after cancer treatment. However, as adolescent and young adult
(AYA) cancer is rare, and only recently recognized as specialty, health
professionals may not have the skills, competence, and confidence to meet the
needs of the young patient with cancer. The aim of this study was to identify the
learning needs of health professionals providing cancer care to adolescents and
young adults before and following the introduction of a state-wide AYA cancer
education program. METHODS: A survey of educational needs of health professionals
was undertaken in 2013 at the commencement of the Queensland Youth Cancer
Service. The survey was used to develop the education program of the service. The
education program was delivered across the state in a variety of formats,
covering a range of topics throughout 2013-2016. The second survey was completed
in 2017. Results were compared to identify if educational needs or the self-rated
confidence of health professionals in regard to AYA cancer care had changed over
time. RESULTS: One hundred twenty-two participants completed the first survey and
73 completed the second. The most prominent educational needs in 2013 were
palliative care and biomedical topics such as understanding AYA growth and
development as well as specific AYA cancers and treatment. The second survey
identified that palliative care education remained important; however, there was
a shift toward health professionals request for more psychosocial and practical
education on topics including fertility, sexuality, and managing late effects.
CONCLUSION: To provide high-quality healthcare to AYAs with cancer, health
professionals require ongoing opportunities for education and training.
PMID- 29336667
TI - Influence of long-term consumption of bitter apricot seeds on risk factors for
cardiovascular diseases.
AB - The present study was designed to reveal whether long-term consumption of bitter
apricot seeds causes changes in lipid profile and other risk factors for
cardiovascular diseases. The study group consisted of 12 healthy adult volunteers
(5 females and 7 males). The average age of women was 41.60 +/- 11.28 years and
the average age of men was 36.71 +/- 13.70 years. Volunteers consumed 60 mg kg-1
of body weight of bitter apricot seeds divided into 8-12 doses daily for 12
weeks. Volunteers were recruited from the general population of Slovak Republic.
After 12 weeks, mean body weight of the participants increased from 77.34 to
78.22 kg (P > 0.05). The average total cholesterol levels decreased from 4.86
mmol L-1 at the beginning of the study to 4.44 mmol L-1 at the end of the study
(P < 0.05). We did not observe any significant increase in high-density
cholesterol (from 1.55 to 1.60 mmol L-1). The average low-density cholesterol
levels decreased from 2.93 mmol L-1 at the beginning of the study to 2.31 mmol L
1 at the end of the study (P < 0.001). Concentration of triglycerides increased
significantly over the 12-week intervention period from 0.84 to 1.17 mmol L-1.
After the intervention, the high-sensitivity C-reactive protein level decreased
from 1.92 to 1.23 mg L-1, but results were non-significant (P > 0.05). Creatine
kinase serum levels increased from 2.31 to 2.77 mg L-1 (P > 0.05) over the 12
week intervention period. The results suggest that regular intake of bitter
apricot seeds may be considered potentially useful for prevention of
cardiovascular diseases.
PMID- 29336668
TI - Safety and biodistribution of sulfated archaeal glycolipid archaeosomes as
vaccine adjuvants.
AB - Archaeosomes are liposomes comprised of ether lipids derived from various
archaea. Unlike conventional ester-linked liposomes, archaeosomes exhibit high pH
and thermal stability. As adjuvants, archaeosomes can induce robust, long-lasting
humoral and cell-mediated immune responses and enhance protection in murine
models of infectious disease and cancer. Archaeosomes constituted with total
polar lipids (TPL) of various archaea are relatively complex, comprising >10
different lipid compounds. Archaeosomes can be constituted with semi-synthetic
glycerolipids built on ether-linked isoprenoid phytanyl cores with varied
synthetic glycol- and amino-head groups. However, such semi-synthetic
archaeosomes involve many synthetic steps to arrive at the final desired
glycolipid composition. We have developed a novel archaeosome formulation
comprising a sulfated saccharide group covalently linked to the free sn-1
hydroxyl backbone of an archaeal core lipid (sulfated S-lactosylarchaeol, SLA)
mixed with uncharged glycolipid (lactosylarchaeol, LA). This new class of
adjuvants can be easily synthesized and retains strong immunostimulatory activity
for induction of cell-mediated immunity following systemic immunization. Herein,
we demonstrate the safety of SLA/LA archaeosomes following intramuscular
injection to mice and evaluate the immunogenicity, in vivo distribution and
cellular uptake of antigen (ovalbumin) encapsulated into SLA/LA archaeosomes.
Overall, we have found that semi-synthetic sulfated glycolipid archaeosomes are a
safe and effective novel class of adjuvants capable of inducing strong antigen
specific immune responses in mice and protection against subsequent B16 melanoma
tumor challenge. A key step in their mechanism of action appears to be the
recruitment of immune cells to the injection site and the subsequent trafficking
of antigen to local draining lymph nodes.
PMID- 29336669
TI - First-line treatment of apatinib in elderly patient of advanced gastric
carcinoma: A case report of NGS-driven targeted therapy.
AB - Gastric carcinoma (GC) is a common gastrointestinal malignancy with high
incidence and mortality worldwide, and most patients are diagnosed in the late
stages of disease. Palliative chemotherapy provides a survival benefit for
patients with inoperable advanced GC. However, elderly patients who are unable to
tolerate chemotherapy had worse prognosis due to lack of effective treatment.
Herein we reported a Chinese elderly GC patient using next generation sequencing
(NGS)-based tumor DNA analysis. Valuable gene variants of vascular endothelial
growth factor (VEGF) A gene amplification were detected. Additionally, a novel
NOTCH1-BPHL fusion has been identified. He received antiangiogenic drug apatinib
and showed both good clinical and radiographic response, but eventually died of
non-cancer related cause, with progression free survival time (PFS) and overall
survival time (OS) up to 9.53 months. This was the first GC case with apatinib
usage as first-line treatment under the guidance of NGS gene profiling.
PMID- 29336670
TI - Does Drug Use Inhibit Crime Deceleration or Does Crime Inhibit Drug Use
Deceleration? A Test of the Reciprocal Risk Postulate of the Worst of Both Worlds
Hypothesis.
AB - BACKGROUND: Prior research has shown that ongoing drug use inhibits the commonly
reported maturing out of crime process and that ongoing crime inhibits the
commonly reported maturing out of drug use process. OBJECTIVES: To test the
predictive efficacy of drug use for crime deceleration and of crime for drug
deceleration using a prospective analysis of data on a group of 524 male
California Youth Authority parolees to see if both effects exist simultaneously.
METHOD: A two-equation regression analysis of Year 3 arrests and illicit drug use
was performed, controlling for age, race, marital status, employment status, and
number of months free in the community. RESULTS: It was determined that illicit
drug use at Year 2 predicted an increase in arrests between the first and third
years of the analysis and arrests at Year 2 predicted an increase in illicit drug
use over this same time period. Alcohol use, on the other hand, failed to predict
a change in arrests and arrests failed to predict a change in alcohol use.
CONCLUSIONS: The results of this study suggest that illicit drug use may inhibit
the natural maturing out of crime process observed in emerging adults whereas
involvement in crime may inhibit the natural maturing out of illicit drug use
process. These findings not only support the reciprocal risk postulate from the
Worst of Both Worlds hypothesis but also have implications for risk prediction,
risk management, and treatment.
PMID- 29336671
TI - The Indirect Effect of Ethnic Identity on Marijuana Use Through School
Engagement: An African American High School Sample.
AB - BACKGROUND: African American marijuana use is associated with many negative
social, emotional, and health-related consequences. Of significance, over recent
years this population has shown an increase in use. In the literature, ethnic
identity and school engagement are prominent protective factors against substance
use. OBJECTIVE: This study will examine how these protective factors are related,
specifically whether ethnic identity mitigates risk through school engagement to
reduce marijuana use. METHOD: A path analysis was conducted with 437 African
American high school students (41% male) from Midwestern schools to examine the
role of school engagement in the relationship between ethnic identity and
marijuana use. RESULTS: The results revealed that students high in ethnic
identity have higher school engagement, which lessens their frequency of
marijuana use. Therefore, ethnic identity reduces marijuana use by increasing
student's school engagement. Conclusions/Importance: The results offer a clearer
picture of how ethnic identity and school engagement protect against marijuana
use. The results also present insight into how to protect students who are low in
ethnic identity.
PMID- 29336672
TI - Internal Cs+ inhibits root elongation in rice.
AB - The root system anchors the plant to the soil and contributes to plant autotrophy
by taking up nutrients and water. In relation with this nutritional function,
root development is largely impacted by availability of nutrients and water. Due
to human activity, plants, in particular crops, can also be exposed to pollutants
which can be absorbed and incorporated into the food chain. Cesium in soils is
present at non-toxic concentrations for the plant (micromolar or less), even in
soils highly polluted with radioactive cesium due to nuclear accidents. Here, we
report on the morphological response of rice roots to Cs+ at micromolar
concentrations. It is shown that Cs+ reduces root elongation without affecting
root dry weight. Noteworthy, inactivation of the Cs+-permeable K+ transporter
OsHAK1 prevents such effect of Cs+, suggesting that internal Cs+ triggers the
modification of the root system.
PMID- 29336673
TI - A practical synthesis of xylo- and arabinofuranoside precursors by
diastereoselective reduction using Corey-Bakshi-Shibata catalyst.
AB - The Corey-Bakshi-Shibata (CBS) catalyst provides an efficient mechanism to reduce
ketones and achieve desired enantiopure alcohols. Herein, the diastereoselective
reduction of C-2' and C-3'-keto ribofuranoside derivatives to the corresponding
arabino- and xylofuranosides in greater than 95% diastereomeric excess is
reported. The stereo-directed substitution with an azido group as well as the
synthesis of prodrugs cytarabine and vidarabine are also described. The reported
strategy offers superior diastereoselectivity, shorter reaction times, and
obviates cooling required with comparable protocols involving achiral reductants.
PMID- 29336674
TI - A facile synthesis of novel pyrazolopyrimidine thioglycosides as purine
thioglycoside analogues.
AB - The easy, convenient and high yielding preparation of new thioglycosides
incorporating mercaptopyrazolo[1,5-a]pyrimidine moieties from readily accessible
starting materials has been reported. The main step of this protocol is the
formation of 7-mercaptopyrazolo[1,5-a]pyrimidine-6-carbonitrile derivatives 4a-d
by condensation of sodium 2-cyano-3-ethoxy-3-oxoprop-1-ene-1,1-bis(thiolate) 1
with 4-(aryldiazenyl)-1H-pyrazole-3,5-diamines 3a-d to form target compounds 4a
d, which coupled with tetra-O-acetyl-alpha-D-glycopyranosyl bromides 5a,b in the
presence of basic medium to provide the corresponding product purine
thioglycoside analogs 6a-h. Ammonolysis of the latter compounds 6a-d at ambient
temperature for 10 minutes, led to the free glycoside derivatives 7a-h, which
were obtained in approximately quantitative yields. Their structures were created
based on the spectroscopic and elemental data.
PMID- 29336675
TI - Synthesis and cytotoxic activity of novel acyclic nucleoside analogues with
functionality in click chemistry.
AB - We describe synthesis of novel acyclic nucleoside analogues which are building
blocks for CuAAC reaction and their activity against two types of human cancer
cell lines (HeLa, KB). Three of chosen compounds show promising cytotoxic
activity. Synthesis pathway starting from simple and easily accessible substrates
employing DMT or TBDPS protective groups is described. Adenosine and thymidine
analogues containing alkyne moiety and adenosine analogue containing azido group
were synthesized. The obtained units showed ability of forming triazole motif
under the CuAAC reaction conditions.
PMID- 29336676
TI - Vasopressors in Sepsis.
AB - BACKGROUND: Sepsis accounts for 10% of intensive care unit admissions and
significant healthcare costs. Although the mortality rate from sepsis has been
decreasing with better critical care, early identification of septic patients,
and prompt interventions, the mortality rate remains 20%-30%. METHOD: Review of
the English-language literature. RESULTS: Norepinephrine is the first-line
vasopressor in shock and is associated with a lower mortality rate as well as
fewer adverse effects. Dopamine has similar actions but is associated with
significantly more tachydysrhythmias and should be reserved for patients with
bradycardia. Epinephrine and vasopressin are appropriate second-line vasopressors
and may enable use of lower doses of norepinephrine while improving hemodynamics.
Inotropes may be added in patients with cardiac dysfunction. CONCLUSION:
Appropriate treatment of sepsis includes prompt identification, early
antimicrobial drug therapy, appropriate fluid resuscitation, and initiation of
vasopressors in the presence of continued septic shock. Further research needs to
be done to better understand the ideal timing of the addition of a second agent
and the optimal combinations of vasopressors for individual patients.
PMID- 29336677
TI - Molecular Screening Versus Phenotypic Susceptibility Testing of Multidrug
Resistant Mycobacterium tuberculosis Isolates for Streptomycin and Ethambutol.
AB - Proper management of multidrug-resistant tuberculosis (MDR-TB) requires accurate
drug susceptibility testing (DST) of Mycobacterium tuberculosis isolates to other
(ethambutol [EMB], pyrazinamide, and streptomycin [SM]) first-line drugs. This
study compared the performance of Mycobacterium Growth Indicator Tube (MGIT) 960
system for DST of MDR-TB isolates with polymerase chain reaction (PCR) sequencing
of embB, rpsL, and rrs genes for detecting resistance to EMB and SM. MDR-TB
strains (n = 60) and 25 pansusceptible M. tuberculosis isolates collected during
2011-2016 were tested. Phenotypic DST was performed by MGIT 960 system by using
SIRE drug kit. EMB and SM resistance-conferring mutations in embB and rpsL+rrs
genes, respectively, were detected by PCR sequencing. No mutations were detected
in pansusceptible isolates. Among 60 MDR-TB strains, 35 of 40 SM-resistant and
none of 20 SM-susceptible isolates contained rpsL and/or rrs mutations (kappa =
0.82, very good agreement). However, all 18 EMB-resistant MDR-TB strains and 33
of 42 EMB-susceptible MDR-TB strains contained an embB mutation (kappa = 0.14,
poor agreement). Thus, 40 of 60 (67%) and 35 of 60 (58%) isolates were resistant
to SM (p = 0.451), while 18 of 60 (30%) and 51 of 60 (85%) isolates were
resistant to EMB (p = 0.000) by MGIT 960 system and PCR sequencing, respectively.
MGIT 960 system showed acceptable performance for DST for SM; however, it
performed poorly for EMB as many MDR-TB strains with embB mutations, which confer
low-level resistance to EMB, were detected as EMB susceptible. Molecular
screening for resistance-conferring mutations in embB gene is thus superior to
MGIT 960 system when accurate EMB susceptibility results are needed for proper
management of MDR-TB patients.
PMID- 29336678
TI - Phylogeny and diversity of the morphologically similar polypore genera
Rigidoporus, Physisporinus, Oxyporus, and Leucophellinus.
AB - Rigidoporus and its morphologically similar genera Physisporinus, Oxyporus, and
Leucophellinus, which include some forest pathogens and medicinal species, are
very important groups of wood-decaying fungi. Species of these genera have not
only ecological functions, but also economic importance. Phylogenetic and
taxonomic studies on taxa in these genera were carried out. Inferred from
phylogenies based on DNA sequences of the nuc rDNA ITS1-5.8S-ITS2 (internal
transcribed spacer [ITS]) and D1-D2 domains of nuc 28S rDNA, 36 species sampled
that traditionally belong to Physisporinus, Rigidoporus, Leucophellinus, and
Oxyporus are nested mostly in eight lineages. Of these lineages, five (including
four genera of Physisporinus, Emmia, Flaviporus, and Flavodon and one taxon "R.
hypobrunneus") belong to Polyporales and three (including the genera Rigidoporus,
Bridgeoporus, and Leucophellinus) belong to Hymenochaetales. Rigidoporus and
Oxyporus are merged because the type species of both genera are nested in a
single lineage within Hymenochaetales. Some taxon previously placed in Ceriporia
and Oxyporus are transferred to Emmia and Flavodon, respectively, on the basis of
current phylogeny. Utilizing a combination of the morphological and phylogenetic
evidence, 16 new combinations in Bridgeoporus, Emmia, Flaviporus, Flavodon,
Rigidoporus, and Physisporinus are proposed. Five new species, Physisporinus
crataegi, P. lavendulus, P. subcrocatus, P. tibeticus, and Rigidoporus
submicroporus, are recognized from China. Illustrated descriptions of these novel
species are provided. Three taxa are treated at the generic level of
Physisporinus because of limited samples.
PMID- 29336679
TI - Arcobacter butzleri Ciprofloxacin Resistance: Point Mutations in DNA Gyrase A and
Role on Fitness Cost.
AB - Arcobacter butzleri is a widely distributed emerging pathogen resistant to
various classes of antimicrobial agents, namely fluoroquinolones. A. butzleri
resistance to fluoroquinolones is conferred by point mutations at the antibiotic
target. The aim of this study was to evaluate mutations at gyrA associated with
ciprofloxacin resistance and evaluate whether acquisition of resistance impacts
on fitness and stress tolerance of A. butzleri. A. butzleri ciprofloxacin mutants
were generated by laboratory induction. Identification of mutations associated
with ciprofloxacin resistance was performed by gyrA sequencing. Growth kinetics,
cost of fitness, biofilm formation ability, and stress tolerance were assessed.
Two amino acid substitutions in the quinolone resistance-determining region of
GyrA were identified in the mutant strains, one previously described (Thr-85-Ile)
and a new substitution (Asp-89-Tyr). No differences in growth kinetics were
recorded between parental and mutant strains; however, fitness cost was variable,
according to the genetic background of the strains, and independently of
ciprofloxacin resistance. Overall, the ciprofloxacin resistance development did
not significantly affect stress tolerance, motility, or biofilm-forming ability.
In conclusion, acquisition of ciprofloxacin resistance in A. butzleri is
associated with mutations in gyrA and is likely well compensated, with cost of
fitness reflecting the diversity in genetic background of this bacterium.
PMID- 29336680
TI - Relating soil geochemical properties to arsenic bioaccessibility through
hierarchical modeling.
AB - Interest in improved understanding of relationships among soil properties and
arsenic (As) bioaccessibility has motivated the use of regression models for As
bioaccessibility prediction. However, limits in the numbers and types of soils
included in previous studies restrict the usefulness of these models beyond the
range of soil conditions evaluated, as evidenced by reduced predictive
performance when applied to new data. In response, hierarchical models that
consider variability in relationships among soil properties and As
bioaccessibility across geographic locations and contaminant sources were
developed to predict As bioaccessibility in 139 soils on both a mass fraction
(mg/kg) and % basis. The hierarchical approach improved the estimation of As
bioaccessibility in studied soils. In addition, the number of soil elements
identified as statistically significant explanatory variables increased when
compared to previous investigations. Specifically, total soil Fe, P, Ca, Co, and
V were significant explanatory variables in both models, while total As, Cd, Cu,
Ni, and Zn were also significant in the mass fraction model and Mg was
significant in the % model. This developed hierarchical approach provides a novel
tool to (1) explore relationships between soil properties and As bioaccessibility
across a broad range of soil types and As contaminant sources encountered in the
environment and (2) identify areas of future mechanistic research to better
understand the complexity of interactions between soil properties and As
bioaccessibility.
PMID- 29336681
TI - Exposure to firework chemicals from production factories in pregnant women and
risk of preterm birth occurrence in Liuyang, China.
AB - In the production of fireworks, various pollutants including particles of metals
and organic compounds are released into the environment. Although the adverse
effects of these air pollutants are known, the impact on pregnant women residing
in this area remains to be determined. The aim of this study was to examine the
association between maternal exposure to fireworks production chemicals and
frequency of preterm birth in Liuyang, China. Maternal exposure to fireworks
production was estimated at the residential district level and assessed using
factory density, which was defined as the number of fireworks factories per 1000
residents in each district. The association of maternal exposure to particulates
released from fireworks production plants with frequency of preterm birth was
determined using data obtained from a cohort study conducted in Liuyang, China.
Data were analyzed utilizing linear regression and logistic regression. There was
no significant association between factory density and spontaneous preterm or
medically induced preterm birth. Unexpectedly, pregnant women residing in areas
with higher density of fireworks factories were at a reduced risk of preterm
premature rupture of membranes (PPROM). Data demonstrated that residential
density of fireworks factories appeared to be negatively correlated with preterm
birth rate as evidenced by PPROM. At present, it is difficult to reconcile the
inverse relationship between firework chemical exposure and frequency of preterm
births as ambient particulate inhalation is known to adversely affect preterm
birth occurrence.
PMID- 29336682
TI - Preliminary phylogeny of Coemansia (Kickxellales), with descriptions of four new
species from Taiwan.
AB - Four new species of Coemansia from Taiwan are described. Three produce spirally
twisted sporangiophores, and these new taxa increase the number of species in the
Coemansia spiralis complex from three to six. Each new taxon is morphologically
unique. Coemansia biformis, sp. nov., has two different asexual reproductive
types on the same thallus; one is straight and the other has a spiral fertile
region. Coemansia helicoidea, sp. nov., has stoloniferous sporangiophores with a
helicoid fertile region. Coemansia pennisetoides, sp. nov., has a sporangiophore
with a fertile region that resembles the inflorescence of the plant genus
Pennisetum. Coemansia umbellata, sp. nov., has an umbellate sporangiophore
branching pattern and a spirally twisted fertile region on the lowest branches. A
dichotomous key was provided to identify the 23 accepted Coemansia species.
Phylogenetic analysis based on a combined data set of D1-D2 domains of nuc 28S
ribosomal RNA (rDNA) and partial nuc 18S rDNA identifies several independent
evolutionary lineages within Coemansia and suggests that Spirodactylon aureum and
Kickxella alabastrina may be nested within the genus Coemansia. Sequences of nuc
rDNA ITS1-5.8S-ITS2 (internal transcribed spacer [ITS] barcode) are also used to
support the description of these new species of Coemansia.
PMID- 29336683
TI - Adsorption of 2,4-dichlorophenoxyacetic acid and 4-chloro-2-metylphenoxyacetic
acid onto activated carbons derived from various lignocellulosic materials.
AB - Adsorption of 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2
metylphenoxyacetic acid (MCPA) from aqueous solution onto activated carbons
derived from various lignocellulosic materials including willow, miscanthus,
flax, and hemp shives was investigated. The adsorption kinetic data were analyzed
using two kinetic models: the pseudo-first order and pseudo-second order
equations. The adsorption kinetics of both herbicides was better represented by
the pseudo-second order model. The adsorption isotherms of 2,4-D and MCPA on the
activated carbons were analyzed using the Freundlich and Langmuir isotherm
models. The equilibrium data followed the Langmuir isotherm. The effect of pH on
the adsorption was also studied. The results showed that the activated carbons
prepared from the lignocellulosic materials are efficient adsorbents for the
removal of 2,4-D and MCPA from aqueous solutions.
PMID- 29336684
TI - A Systematic Search and Review of Adult-Targeted Overweight and Obesity
Prevention Mass Media Campaigns and Their Evaluation: 2000-2017.
AB - Mass media campaigns are a commonly used strategy in public health. However, no
review has assessed whether the design and evaluation of overweight and obesity
campaigns meets best practice recommendations. This study aimed to fill this gap.
We systematically searched five databases for peer-reviewed articles describing
adult-targeted obesity mass media campaigns published between 2000 and 2017,
complemented by reference list searches and contact with authors and agencies
responsible for the campaigns. We extracted data on campaign design,
implementation, and evaluation from eligible publications and conducted a
qualitative review of 29 publications reporting on 14 campaigns. We found a need
for formative research with target audiences to ensure campaigns focus on the
most salient issues. Further, we noted that most campaigns targeted individual
behaviors, despite calls for campaigns to also focus upstream and to address
social determinants of obesity. Television was the dominant communication channel
but, with the rapid advance of digital media, evaluation of other channels, such
as social media, is increasingly important. Finally, although evaluation methods
varied in quality, the evidence suggests that campaigns can have an impact on
intermediate outcomes, such as knowledge and attitudes. However, evidence is
still limited as to whether campaigns can influence behavior change.
PMID- 29336685
TI - Seroprevalence of Q Fever Among the Indigenous People (Orang Asli) of Peninsular
Malaysia.
AB - Q fever is a disease caused by Coxiella burnetii. It is a disease of public
health concern in many parts of the world. In this study, we described the
seroprevalence of Q fever among selected populations of Orang Asli (OA),
indigenous people, many of whom live within the forest fringe areas of Peninsular
Malaysia. Serum samples were obtained from 887 OA participants from selected
villages. Samples were analyzed for the presence of IgG antibodies reactive
against C. burnetii by enzyme-linked immunosorbent assay. Statistical methods
were used to identify possible associations between seropositivity for C.
burnetii and a number of demographic variables obtained from the questionnaires.
In total, 9.6% (n = 85/887) of the serum samples were reactive to C. burnetii.
Statistical results suggest that elderly male OA residing in OA village, Bukit
Payung, were most likely to be tested seropositive for C. burnetii. This study
suggests that OA are at a significant risk of contracting C. burnetii infection,
and both demographic and geographic factors are important contributors to this
risk. Further prospective studies are needed to establish the true burden of C.
burnetii infection within the indigenous population as well as within Peninsular
Malaysia as a whole.
PMID- 29336686
TI - Phylogeny and taxonomy of Favolus (Basidiomycota).
AB - Favolus is a natural genus that is closely related to Polyporus. A taxonomic
study of Favolus was carried out based on morphological characteristics and
phylogenetic analysis of the internal transcribed spacer (ITS) region (ITS1-5.8S
ITS2 = ITS) and 18S and 28S genes of the nuc rDNA, translation elongation factor
1-alpha gene (TEF1-alpha), the mt 16S rDNA gene (mt rrnS), beta-tubulin gene
(TBB1), and the RNA polymerase II largest subunit (RPB1) and second largest
subunit (RPB2) genes. Fourteen specimens collected from subtropical to tropical
regions in China were shown to be different from existing Favolus species. They
are described and illustrated here as four new species, namely, Favolus niveus,
F. septatus, F. pseudoemerici, and F. subtropicus.
PMID- 29336687
TI - Reasons why undergraduate women comply with unwanted, non-coercive sexual
advances: A serial indirect effect model integrating sexual script theory and
sexual self-control perspectives.
AB - This study explored the predictors of young women's compliance with unwanted
sexual activities, integrating the social with the cognitive and behavioral
correlates of sexual compliance. In total, 222 young heterosexual women completed
measures examining the Sexual Self-Control model, including reasons for
consenting, sexual resourcefulness, and compliance with unwanted sex, as well as
gender role measures pertaining to sexual script theory, including the sexual
double standard, gender role stress, and virginity scripts. An exploratory
analysis of serial indirect effects demonstrated that women scoring lower in
sexual resourcefulness endorsed higher female gender role stress, which in turn
was associated with higher endorsement of reasons for consent, translating into
more frequent compliance with unwanted sexual activities. The relationship
between one's ability to refuse and their decision to refuse appears quite
complex. Understanding one's decision requires consideration of the social
aspects of gender role endorsement.
PMID- 29336688
TI - Beliefs about Memory as a Mediator of Relations between Metacognitive Beliefs and
Actual Memory Performance.
AB - The goal of the present study was to investigate relationships between personal
beliefs about memory, metacognitive beliefs, and actual memory performance. One
hundred thirty-seven participants' (aged 20 to 60 years) metacognitive beliefs
were measured using the Metacognition Questionnaire (MCQ-30), memory beliefs were
measured using the Personal Beliefs about Memory Instrument (PBMI), and an
episodic memory task was used to measure actual memory performance, memory
predictions, and postdictions. Younger adults had lower scores on the positive
beliefs subfactor of the MCQ-30, higher scores on retrospective change and
control subfactors of the PBMI, and outperformed middle-aged adults on recall and
recall postdiction. Path analysis showed that individuals' beliefs about memory
mediate the relationship between metacognitive beliefs and actual memory
performance. Specifically, low lack of confidence (or less worry) in one's own
memory and attentional capabilities was related to higher memory performance and
positive personal beliefs regarding specific memory ability mediated
relationship.
PMID- 29336689
TI - A Molecular Survey of Tick-Borne Pathogens from Ticks Collected in Central
Queensland, Australia.
AB - Central Queensland (CQ) is a large and isolated, low population density, remote
tropical region of Australia with a varied environment. The region has a diverse
fauna and several species of ticks that feed upon that fauna. This study examined
518 individual ticks: 177 Rhipicephalus sanguineus (brown dog tick), 123
Haemaphysalis bancrofti (wallaby tick), 102 Rhipicephalus australis (Australian
cattle tick), 47 Amblyomma triguttatum (ornate kangaroo tick), 57 Ixodes
holocyclus (paralysis tick), 9 Bothriocroton tachyglossi (CQ short-beaked echidna
tick), and 3 Ornithodoros capensis (seabird soft tick). Tick midguts were pooled
by common host or environment and screened for four genera of tick-borne zoonoses
by PCR and sequencing. The study examined a total of 157 midgut pools of which 3
contained DNA of Coxiella burnetii, 13 Rickettsia gravesii, 1 Rickettsia felis,
and 4 other Rickettsia spp. No Borrelia spp. or Babesia spp. DNA were recovered.
PMID- 29336690
TI - Advanced glaucoma at presentation is associated with poor follow-up among
glaucoma patients attending a tertiary eye facility in Southern Nigeria.
AB - PURPOSE: Globally, particularly in Africa, poor compliance with medication is a
major problem in glaucoma management but little is known about follow-up rates
among African glaucoma patients. The aim of this study was to determine rates of
follow-up among glaucoma patients attending a tertiary hospital in southern
Nigeria and investigate predictors of poor follow-up. METHODS: Data were
extracted from medical records of new glaucoma patients who attended the hospital
between June 2011 and May 2013. Socio-demographic and clinical parameters (visual
acuity; stage of glaucoma) recorded at diagnosis were extracted using a pre
tested form. Follow-up was defined as good if they had attended within 9 months
of the study date, inadequate when the last follow-up was more than 9 months and
failed if they did not attend any follow-up or the most recent visit was more
than 14 months from the study date. Univariate and multivariable analyses were
undertaken to explore predictors of poor follow-up (inadequate plus failed).
RESULTS: Three hundred forty-eight patients were recruited, 54% were male and the
mean age was 52.7 (range 16-88) years. Follow-up was as follows: good 28.4%,
inadequate 46.6%, failed 25%. Overall, 71.6% had poor follow-up. Independent
predictors of poor follow-up were poorer visual acuity (OR 3.85, 95% confidence
interval (CI) 1.25-11.80 for visual impairment; OR 4.11, 95% CI 1.32-12.81 for
blind) and end-stage glaucoma (OR 3.55 (1.31-9.62), p = 0.01). CONCLUSION:
Enhanced counselling of patients with moderate to advanced glaucoma and visual
impairment is required to improve follow-up and hence glaucoma management.
PMID- 29336691
TI - The evaluation of Cr-curcumin-DNA complexation by experimental and theoretical
approaches.
AB - Chromium(III) chloride mediates DNA-DNA cross-linking. Some chromium complexes
promote programmed cell death in specific ligand environment through binding to
DNA. One strategy that can be supposed for reduction of Cr3+ binding affinity to
DNA is using curcumin as a chelator. In the current study, the
[Cr(Curcumin)(EtOH)2](NO3)2 (CCC) was synthesized and characterized by UV/Vis, FT
IR, CHN and spectrophotometric titration techniques. The mole ratio plot revealed
a 1:1 complex between Cr3+ and curcumin in solution. Binding interaction of this
complex with calf thymus-DNA (CT-DNA) was investigated using UV/Vis, circular
dichroism (CD), FT-IR and cyclic voltammetry. The intrinsic binding constants of
CCC with DNA, measured by UV/Vis and cyclic voltammetry, were 1.60 * 105 and 1.13
* 105, respectively. The thermodynamic studies showed that the reaction is
enthalpy and entropy favoured. CD analysis revealed that only Lambda-CCC
interacts with DNA and Delta-CCC form has no tendency towards DNA. Based on FT-IR
studies, it was understood that CCC interacts with DNA via minor groove binding.
The docking simulation was carried out for finding the binding mode of CCC to
DNA, too. All of data demonstrated that the curcumin significantly reduced the
affinity of Cr3+ to the DNA and the form of Delta-CCC has no interaction with
DNA.
PMID- 29336692
TI - The First Serological Study of Q Fever in Humans in Lebanon.
AB - OBJECTIVE: The aim of this study was to estimate, for the first time, the human
seroprevalence of Q fever in Lebanon, by assessing the presence of antibodies
against the causative agent, Coxiella burnetii. A total number of 421 serum
samples (226 females and 196 males) were collected in February 2015 from
hospitals and laboratories dispersed in five Lebanese provinces: Akkar, Bekaa,
Mount Lebanon, Nabatieh, and South Lebanon. METHODS: Serial testing approach was
used. Samples were first screened for IgG phase II antibodies against C. burnetii
by Enzyme Linked Immunosorbent Assay (ELISA) Kit. Then, both positive and
inconclusive sera were reexamined by immunofluorescence assay (IFA) test with the
aims to confirm and specify the infection status (past or probably acute
infection) by detecting IgG (I/II) and IgM (I/II) in human sera. RESULTS:
Screening of 421 samples was estimated to be 38.70% (95% CI 34-43.3) positive
samples, 5.90% (95% CI 3.7-8.2) suspect samples (as doubtful results), and 55.40%
(95% CI 50.7-60.1) negative samples. Furthermore, all positive and suspect
samples by ELISA test were retested by immunofluorescence assay test (IFAT), and
the prevalence of positive sample was 37% and the infection case was recorded:
23.75% (95% CI 19.7-27.8) samples resulted from past infection, 1.9% (95% CI 0.6
3.2) probably acute infection characterized by several dominance clinical
symptoms as: fever, cough, headache, difficulty breathing, and atypical
pneumonia, and 0.23% (95% CI 0-0.7) inconclusive sample accompanied by different
symptoms as bone metastasis and lung cancer. CONCLUSION: The study records the
exposition of 37% of 421 patients to C. burnetii distributed in five Lebanese
provinces with the highest seroprevalence in Bekaa and Akkar provinces and the
lowest reported in Mount Lebanon. This difference may be due to the presence of
high density of livestock production and of major agricultural areas in these two
provinces.
PMID- 29336693
TI - Self-Other Differentiation Scale: Dimensionality, IRT Parameterization, and
Measurement Invariance.
AB - The Self-Other Differentiation Scale (Olver, Aries, & Batgos, 1989 ) is a self
report instrument assessing the experience of a separate sense of self from
others. The authors aimed to examine its dimensionality, reliability, and
measurement invariance across gender. It was completed by 348 participants (48%
men) from 17 to 30 years old in Study 1, 348 participants (40% men) from 18 to 28
years old in Study 2, and 1,068 participants (49% men) from 17 to 28 years old in
Study 3. The results supported the hypothesis of just one factor underlying the
scale; they also showed an appropriate internal consistency and a partial
measurement invariance across gender. Results also showed evidence for a 10-item
version of the scale. Globally, the Self-Other Differentiation Scale can be
considered a good scale to assess individual's sense of differentiation of one's
own sense of self from others.
PMID- 29336694
TI - "It has changed my whole life": The systemic implications of chronic low back
pain among older adults.
AB - Chronic low back pain (CLBP) is the most common pain complaint among older
adults. Despite its prevalence, very little research has qualitatively examined
the diverse consequences of living with CLBP in later life. As part of a larger
study aiming to understand the experience of CLBP among older adults, the
objective of this manuscript is to understand how older adults experience CLBP
and its impacts on the functioning of older adults. Guided by van Manen's
phenomenological method, 23 semi-structured interviews with 21 pain clinic
patients aged 66-83 were conducted. Through an iterative process assisted by
NVivo 11 software, researchers used line-by-line thematic coding to identify main
impacts of CLBP. Under the main theme "It has changed my whole life," results are
reflected in six subthemes: (a) Pain damages sense of self; (b) trapped in a body
that doesn't work anymore; (c) me, my partner, and my pain; (d) pain complicates
family relationships; (e) painfully employed; and (f) feeling socially and
recreationally repressed. This study improves our understanding of older pain
clinic patients' experience of living with debilitating CLBP and offers direction
for social work intervention in the context of multidisciplinary pain management.
PMID- 29336695
TI - "Ghosts from the past": The re-emergence of internalized religious stigma
following diagnosis of HIV among Northern Irish gay men.
AB - This article explores how previous exposure to religious homonegativity features
in the sense-making process following HIV diagnosis in a homogenous sample of six
gay men living in Northern Ireland. Interpretive phenomenological analysis was
used to identify two key overarching themes: Negotiating authenticity in unsafe
space, which relates to the experience of negotiating same-sex attraction within
religious environments, and Re-emergence of religious shame in diagnosis, which
relates to the way in which the men made sense of diagnosis from the position of
having been exposed to religious homonegativity earlier in their lives. Findings
demonstrate how the men negotiated their sexual orientation within religious
contexts and how a reconstruction of God was necessary to preserve an authentic
sense of self. Despite reaching reconciliation, HIV was initially appraised
within a retributive religious framework that served to temporarily reinforce
previously learned shame-based models of understanding this aspect of the self.
PMID- 29336696
TI - Controlled Adverse Environment Chambers in Dry Eye Research.
AB - Dry eye disease (DED) is a common condition with signs and symptoms that vary
depending on a wide range of environmental factors to which people are exposed in
their daily lives. Factors such as variable temperature, airflow velocity,
relative humidity, seasonality, and pollutants can alter the rate of tear film
evaporation, improving or exacerbating symptoms of DED. Results from currently
available clinical tests do not always correlate well with patient-reported
symptoms, and the continually changing environment and variability in DED
symptoms present challenges for the design and conduct of clinical trials.
Controlled adverse environment chambers allow standardization of temperature,
humidity, and airflow and may minimize potential confounding factors in clinical
investigations. Their use can promote accurate study of the pathophysiology of
DED, discovery of disease biomarkers, and assessment of the effect of various
therapeutic approaches on patients' symptoms. Controlled adverse environment
chambers have been used to simulate indoor surroundings such as airplane cabins
and to test their effects on contact lens wearers. This review summarizes how
these chambers may be useful for the development, approval, and differentiation
of potential new treatments for DED.
PMID- 29336697
TI - Understanding Knowledge, Attitudes, and Behaviors Toward West Nile Virus
Prevention: A Survey of High-Risk Adults in Maryland.
AB - OBJECTIVE: To assess knowledge, attitudes, and behaviors toward West Nile virus
(WNV) prevention among Maryland adults >=60 years old who are at increased risk
of severe WNV disease utilizing the health belief model. METHODS: Using a
stratified random sample of households from zip codes with >=2 human WNV cases,
we conducted a telephone survey of 211 Maryland adults >=60 years old between
October and December 2012. RESULTS: Participants expressing worry about WNV were
over thrice more likely to use insect repellent in the prior 90 days (adjusted
odds ratio [aOR] = 3.46, 95% confidence interval [CI] = 1.33-8.95) and nearly
thrice more likely to drain standing water around their homes than those not
worried (aOR = 2.86, 95% CI = 1.25-6.52). Respondents perceiving a benefit in
paying less for WNV vaccine were more likely to support mosquito control programs
(aOR = 16.00, 95% CI = 1.50-170.68). CONCLUSIONS: Future interventions to promote
WNV prevention among older adults should seek to enhance perceptions of
vulnerability to WNV through risk communication, including media outreach and
written messaging, emphasizing the benefits of personal protective behaviors.
Community partnerships may aid in outreach to this population.
PMID- 29336698
TI - It makes you keep trying: Life review writing for older adults.
AB - Life review writing produces numerous psychosocial benefits for older adults, who
are at risk for isolation and depression. This article shares findings from a
study that examined the experiences of older adults participating in a life
review writing group. The impact of gender composition on the group dynamic was
also explored. Using interpretative phenomenological analysis, this study
explored the experiences of six women and one man who participated in a life
review writing group. Six unifying themes emerged from the research findings: (1)
legacy, (2) connecting with others, (3) reflection, (4) vitality, (5) structure
of the group, and (6) gender dynamics. Implications for theory, practice, and
research are discussed.
PMID- 29336699
TI - Persistent Ambivalence: Theorizing Queer East German Studies.
AB - The German Democratic Republic (GDR; East Germany) had an ambivalent relationship
with homosexuality. Under the principles of socialism, everyone was welcome to
contribute to the greater good. The situation for queer people, here lesbians and
gay men, was different: one of illegality and invisibility. A difficulty in
analyzing these experiences is the theory and methodology necessary to find them
and draw them together in a historical narrative. This essay offers a mode of
analysis in which theories of affect illustrate long-term trends in East German
conceptualizations of same-sex sexuality. By discussing a 1950 court ruling and a
1989 film, the essay demonstrates the persistence of homophobic prejudice and
fear of homosexual seduction of young people and the links to historical and
legal developments.
PMID- 29336700
TI - Effect of Daily Exposure to an Isolated Soy Protein Supplement on Body
Composition, Energy and Macronutrient Intake, Bone Formation Markers, and Lipid
Profile in Children in Colombia.
AB - A soy protein-based supplement may optimize bone health, support physical growth,
and stimulate bone formation. This study aimed to assess the effect of a daily
soy protein supplement (SPS) on nutritional status, bone formation markers, lipid
profile, and daily energy and macronutrient intake in children. One hundred seven
participants (62 girls), ages 2 to 9, started the study and were randomly
assigned to lunch fruit juice with (n = 57, intervention group) or without (n =
50, control group) addition of 45 g (230 Kcal) of a commercial SPS during 12
months; 84 children (51 girls, 33 boys) completed the study (45 and 39
intervention and control, respectively). Nutritional assessment included
anthropometry and nutrient intakes; initial and final blood samples were taken;
insulin-like growth factor-I (IGF-I), osteocalcin, bone specific alkaline
phosphatase (BAP), insulin-like growth factor binding protein-3 (IGFBP-3),
cholesterol, triglycerides, low-density lipoprotein (LDL), and high-density
lipoprotein (HDL) were analyzed. Statistically significant changes (p < .05) in
body mass index and weight for age Z scores were observed between groups while
changes in body composition were not. Changes in energy, total protein, and
carbohydrate intakes were significantly higher in the intervention group (p <
.01). Calorie intake changes were statistically significant between groups (p <
.001), and BAP decreased in both groups, with values within normal ranges.
Osteocalcin, IGFBP-3, and lipid profile were not different between groups. IGF-I
levels and IGF/IGFBP-3 ratio increased significantly in both groups. In
conclusion, changes in macronutrient and energy intake and nutritional status in
the intervention group compared to control group may ensure harmonious and
adequate bone health and development.
PMID- 29336701
TI - Coming Out of the Shadows and the Closet: Visibility Schemas Among Undocuqueer
Immigrants.
AB - Centering the experiences of 31 undocuqueer immigrants, this study seeks to
understand the ways that undocuqueer immigrants negotiate the boundaries of
social performance by revealing or concealing their gender, sexuality, and
immigration status. Findings of this study reveal how, in order to avoid the
constant threat of rejection (both legal and social), undocuqueer immigrants
engage visibility schemas and make strategic decisions about coming out of the
shadows and the closet across different contexts. Undocuqueer immigrants'
narratives reveal the ways the closet resembles the shadows in that both provide
protection from the outside world, yet neither are considered suitable places for
sustaining life. This study raises implications for both research and policy by
considering how the intersection of gender, sexuality, and immigration status
nullifies neoliberal narratives of coming out as an empowering process and
illustrating the uneven landscapes of social acceptance and political control
that undocuqueer immigrants must negotiate.
PMID- 29336702
TI - A health agenda for Green Chemistry.
PMID- 29336704
TI - Intent to use a web-based psychological intervention for partners of cancer
patients: Associated factors and preferences.
AB - This study examined partners of cancer patients intention to use a web-based
psychological intervention, their preferences regarding its preconditions,
functionalities and topics, and factors related to their intention. One hundred
and sixty-eight partners completed a questionnaire about these aspects. Forty
eight percent of the partners would (maybe) make use of a web-based intervention.
Partners who intended to participate were significantly younger, used the
Internet more often, and perceived more caregiver strain. Most partners preferred
an intervention that takes less than 1 hour/week, lasts five weeks or more, and
contains information and peer support. Half of the partners would like to receive
online guidance.
PMID- 29336705
TI - "Thinking about the future, what's gonna happen?"-How young people in Sweden who
neither work nor study perceive life experiences in relation to health and well
being.
AB - PURPOSE: The aim of this study was to explore how young people in Sweden who
neither work nor study perceive life experiences in relation to health and well
being. METHODS: A task-based interview technique was used and data was analysed
with qualitative content analysis. Interviews were conducted with 16 participants
aged 16-20 who were unemployed and not eligible for upper secondary school, or
who had dropped out of school. RESULTS: Three themes emerged from the analysis
illustrating how the young people perceive their life experiences in relation to
health and well-being: Struggling with hardships in the absence of caring
connections, Feeling good when closely connected to others, and Being forced to
question what has been taken for granted. Each theme consists of 2-3 subthemes.
CONCLUSION: Based on the young people's narrated experiences health can be
understood as: something that is created in relation to others and in relation to
the social and cultural context; as something dynamic and changeable; as the
ability to adapt and respond to challenges; and finally as something existing on
a collective as well as an individual level. Implications for school, social
services and health promotion initiatives are discussed, with an emphasis on
working with young people.
PMID- 29336706
TI - Family caregivers' reported nonadherence to the controller medication of asthma
in children in Casablanca (Morocco): Extent and associated factors.
AB - OBJECTIVE: Recent statistics show a relatively high prevalence of asthma among
Moroccan children and a weak control over their symptoms. To our knowledge, no
research has been carried out to document adherence to the controller treatment
in this population. This study aims 1) to assess the extent of children's
nonadherence to the controller treatment of asthma in an urban region of Morocco
as reported by a family caregiver, and 2) to identify the associated factors.
METHODS: We conducted a cross-sectional study among caregivers of asthmatic
children (2-12 years old) in different health and education facilities of
Casablanca-Settat. We administered face-to-face questionnaires incorporating
validated instruments (Medication Adherence Rating Scale-Asthma (MARS-A), Beliefs
about Medicines Questionnaire (BMQ), Asthma Knowledge Questionnaire). Univariate
and multivariate log-binomial regressions evaluating the association between
several factors and reported nonadherence were performed (prevalence ratios (PR)
and 95% confidence intervals (CI)). RESULTS: Through two public hospitals, three
private medical clinics, and one private school, 103 caregivers were recruited.
Low adherence to the controller treatment of asthma was reported by 48% of the
caregivers (MARS-A <45). In the multivariate model, caregivers with the lowest
level of knowledge about asthma were almost three times more likely to report low
adherence compared to caregivers with the highest level (PR = 2.93; 95% CI: 1.14
7.52). CONCLUSIONS: This study highlights the finding that low adherence is
widespread in this context and also the importance of targeting caregivers'
knowledge of asthma for interventions.
PMID- 29336703
TI - Establishing Correlates of Protection for Vaccine Development: Considerations for
the Respiratory Syncytial Virus Vaccine Field.
AB - Correlates of protection (CoPs) can play a significant role in vaccine
development by assisting the selection of vaccine candidates for clinical trials,
supporting clinical trial design and implementation, and simplifying tests of
vaccine modifications. Because of this important role in vaccine development, it
is essential that CoPs be defined by well-designed immunogenicity and efficacy
studies, with attention paid to benefits and limitations. The respiratory
syncytial virus (RSV) field is unique in that a great deal of information about
the humoral response is available from basic research and clinical studies.
Polyclonal and monoclonal antibodies have been used routinely in the clinic to
protect vulnerable infants from infection, providing a wealth of information
about correlations between neutralizing antibodies and disease prevention.
Considerations for the establishment of future CoPs to support RSV vaccine
development in different populations are therefore discussed.
PMID- 29336708
TI - Emergency Dispatcher Stroke Recognition: Associations with Downstream Care.
AB - OBJECTIVE: As the first point of contact for patients activating emergency
medical services (EMS), emergency dispatchers have the earliest opportunity to
recognize stroke. We sought to quantify dispatcher stroke recognition and its
relationships with EMS stroke recognition and response speed. METHODS: We
assembled a cohort of consecutive EMS-transported patients with a dispatcher
suspected stroke or a hospital discharge diagnosis of stroke or transient
ischemic attack (TIA). Dispatcher sensitivity and positive predictive value (PPV)
for stroke recognition were calculated. Multivariable logistic regression
analysis was used to determine predictors of dispatcher recognition and
relationships between dispatcher recognition and downstream care. RESULTS: During
a 12-month period, 601 patients met inclusion criteria. Dispatchers suspected
stroke in 229/324 (sensitivity = 70.7% [65.5 to 75.4%]) confirmed stroke/TIA
cases and correctly assigned a suspected stroke label in 229/506 cases (PPV =
45.3% [41.0 to 49.6%]). Dispatchers had higher odds of recognizing ischemic
strokes (aOR 3.4 [1.4 to 8.5]) and lower odds of recognizing patients with visual
deficits (aOR = 0.4 [0.2 to 0.9]) or vomiting (aOR = 0.3 [0.1 to 0.9]).
Dispatcher suspected stroke cases received more on-scene stroke screens (79.0%
vs. 54.7%, p < 0.0001) and were more often recognized by EMS as strokes (77.7%
vs. 57.9%, p = 0.0005). Dispatcher recognition was independently associated with
EMS stroke recognition (aOR = 3.8 [1.9 to 7.7]), but not with transportation
times, door-to-CT times, or t-PA delivery. CONCLUSIONS: Emergency dispatcher
stroke recognition is associated with higher rates of on-scene stroke scale
performance and EMS ischemic stroke recognition but not with reduced transport
times, door-to-CT times, or t-PA treatment.
PMID- 29336707
TI - Kyasanur Forest Disease Prevalence in Western Ghats Proven and Confirmed by
Recent Outbreak in Maharashtra, India, 2016.
AB - INTRODUCTION: Kyasanur forest disease (KFD) outbreak was confirmed in Dodamarg
Taluka, Sindhudurga district (Maharashtra) in India during the year 2016. The
rise in suspected KFD cases was reported in January 2016, peaked during March,
and then declined gradually from April 2016. The outbreak was thoroughly
investigated considering different socio-clinical parameters. METHODS: Total, 488
suspected KFD cases were investigated using KFD specific real-time RT-PCR and
anti-KFDV IgM enzyme-linked immunosorbent assay (ELISA). Sero-epidemiological
survey was carried out in the affected area using anti-KFDV IgG ELISA. RESULTS:
Among suspected KFD cases, high age-specific attack rate (105.1 per 1000 persons)
was observed in adults (aged 40-59 years). Out of 488 suspected KFD cases, 130
were laboratory confirmed. Of these, 54 cases were KFDV real-time RT-PCR
positive, 66 cases were anti-KFDV IgM ELISA positive and 10 cases were positive
by both the assays. Case fatality ratio among laboratory-confirmed KFD cases were
2.3% (3/130). Majority of laboratory-confirmed KFD cases (93.1%) had visited
Western Ghats forest in Dodamarg for activities like working in cashew nut farms
(79.8%), cashew nut fruit collection (76.6%), collection of firewood (68.5%) and
dry leaves/grass (40.3%), etc., before the start of symptoms. Common clinical
features included fever (100%), headache (93.1%), weakness (84.6%), and myalgia
(83.1%). Hemorrhagic manifestations were observed in nearly one-third of the
laboratory-confirmed KFD cases (28.5%). A seroprevalence of (9.7%, 72/745) was
recorded in KFD-affected area and two neighboring villages (9.1%, 15/165).
Serosurvey conducted in Ker village showed clinical to subclinical ratio of 6:1
in KFD-affected areas. CONCLUSION: This study confirms the outbreak of KFD
Sindhudurg district with 130 cases. Detection of anti-KFDV IgG antibodies among
the healthy population in KFD-affected area during the KFD outbreak suggested the
past exposure of KFD infection. This outbreak investigation has helped health
authorities in adopting KFD vaccination strategy for the population at risk.
PMID- 29336709
TI - Novel Mutation of the Dystrophin Gene in a Child with Duchenne Muscular
Dystrophy.
AB - INTRODUCTION: Duchenne muscular dystrophy (DMD) is an X-linked autosomal
recessive genetic disorder caused by mutations in DMD gene. Approximately 70% of
the mutations are caused by deletions or duplications of DMD exons, while the
remaining were minor mutations. CASE REPORT: We present a 5-year-old boy with
typical clinical features of DMD. A novel mutation was identified as a
c.9358_9359insA of DMD gene by next-generation sequencing. This mutation which
was origined from mother, generated a frameshift mutation and resulted in
abnormal synthesis of protein polypeptide chains. CONCLUSION: We demonstrated a
novel mutation of DMD gene and expanded the spectrum of mutations causing DMD.
PMID- 29336710
TI - Consensus Statement- Prehospital Care of Exertional Heat Stroke.
AB - Exertional heat stroke (EHS) is one of the most common causes of sudden death in
athletes. It also represents a unique medical challenge to the prehospital
healthcare provider due to the time sensitive nature of treatment. In cases of
EHS, when cooling is delayed, there is a significant increase in organ damage,
morbidity, and mortality after 30 minutes, faster than the average EMS transport
and ED evaluation window. The purpose of this document is to present a paradigm
for prehospital healthcare systems to minimize the risk of morbidity and
mortality for EHS patients. With proper planning, EHS can be managed successfully
by the prehospital healthcare provider.
PMID- 29336712
TI - Reliability and minimal detectable change of thoracoabdominal mobility
measurements using photogrammetry.
AB - The knowledge about measurement errors of the measuring tool is important before
its use, as clinical decisions are going to be made based on its results. Here we
investigate intrarater and interrater reliability and the minimal detectable
change (MDC) of thoracoabdominal mobility measurements using photogrammetry,
considering novice and experienced raters. Thoracoabdominal mobility of 17
healthy participants was assessed; photographs during apnea in maximal
inspiration and expiration were used to calculate latero-lateral and
anteroposterior diameters of the thorax (at axillary and xiphoid level) and
abdomen. One novice and one experienced rater measured the same photographs three
times. We found good reliability for the experienced rater (average Intraclass
Correlation Coefficient (ICC): 0.98; average MDC: 0.3) and for interrater
comparison (average ICC: 0.97; average MDC: 0.35) for all measures, with poorer
results for latero-lateral mobility of abdomen. The novice rater presented
moderate reliability for latero-lateral mobility of the thorax at axillary level
and abdomen (ICC: 0.52 and 0.61; MDC: 1.42 and 2.05, respectively) and good
reliability for the other measures (average ICC: 0.81; average MDC: 1.52). The
photogrammetric analysis of thoracoabdominal mobility presented itself as a
reliable method when used by an experienced professional. However, considering
that the measurement of latero-lateral mobility is more subjected to errors, it
should be used with caution. The MDC presented should be taken into account as a
threshold to be certain that the measure is not under the measurement error due
to rater variability.
PMID- 29336711
TI - Circulating serum interleukin-6, serum chitinase-3-like protein-1, and plasma
vascular endothelial growth factor are not predictive for remission and
radiographic progression in patients with early rheumatoid arthritis: post-hoc
explorative and validation studies based on the CIMESTRA and OPERA trials.
AB - OBJECTIVE: To investigate serum interleukin-6 (IL-6), serum chitinase-3-like
protein-1 (YKL-40), and plasma vascular endothelial growth factor (VEGF) as
measures of disease activity and predictors of clinical remission and
radiographic progression in two early rheumatoid arthritis (RA) randomized
controlled trials (RCTs). METHOD: Treatment-naive patients with early RA (< 6
months' duration) and active disease, participating in two investigator-initiated
RCTs, were treated according to a predefined treat-to-target algorithm aiming at
inflammatory control, using methotrexate (MTX) + cyclosporine versus MTX +
placebo (CIMESTRA study, n = 150, 5 year follow-up) or MTX + adalimumab versus
MTX + placebo (OPERA study, n = 180, 2 year follow-up). The 28-joint Disease
Activity Score (DAS28) and conventional radiography [bilateral hands and feet at
baseline, 2 years and 5 years (only CIMESTRA)] were obtained at baseline and
during follow-up. Serum IL-6, serum YKL-40, and plasma VEGF were measured in
baseline blood samples and during follow-up. Hypotheses regarding the biomarkers'
relation with DAS28 and ability to predict clinical remission (DAS28 < 2.6) and
radiographic progression (change in total Sharp van der Heijde score >= 2) were
generated in CIMESTRA and validated in OPERA, by Spearman's correlation and
logistic regression analyses. RESULTS: Baseline IL-6, YKL-40, and VEGF correlated
significantly with DAS28 in CIMESTRA (r = 0.50, r = 0.36, r = 0.36, respectively,
all p < 0.01) and these results were confirmed in OPERA patients (r = 0.52, p <
0.01; r = 0.18, p = 0.01; r = 0.23, p = 0.002, respectively). None of the
biomarkers (absolute values or change) was predictive of clinical remission or
radiographic progression at 2 or 5 years in either study. CONCLUSION: Serum IL-6,
serum YKL-40, and plasma VEGF were significantly correlated with DAS28 at
baseline, but did not have consistent predictive value for clinical remission or
radiographic progression in two early RA RCTs.
PMID- 29336713
TI - Persistent Pulmonary Hypertension Without Underlying Cardiac Disease as a
Presentation of Pulmonary Interstitial Glycogenosis.
AB - INTRODUCTION: Pulmonary interstitial glycogenosis (PIG) is an idiopathic lung
condition that remains clinically underrecognized despite a growing body of
literature. CASE REPORT: We present a case of PIG with pulmonary hypertension
without underlying cardiac disease. This patient presented with respiratory
distress and spontaneous pneumothorax at 6 months of age. Laboratory and imaging
investigations demonstrated nonspecific features, but refractory pulmonary
hypertension was confirmed on cardiac catheterization. Lung tissue histopathology
showed glycogen positive staining of the interstitial cells, consistent with PIG.
CONCLUSION: This unique case demonstrates that pulmonary hypertension can be seen
in the setting of PIG without associated cardiac anomalies, and persists despite
treatment in an otherwise self-limited condition.
PMID- 29336714
TI - Urinary Retention and Medication Utilization on a Palliative Care Unit: A
Retrospective Observational Study.
AB - Urinary retention is a common problem at end-of-life that may be a result of
medications used to control other symptoms. To determine whether use of retention
causing drugs was associated with catheterization for urinary retention among
palliative care unit (PCU) patients, the authors reviewed charts of 91
consecutively admitted patients to a hospital-based PCU. Utilization of eight
classes of retention-causing medications (opioids, antidopaminergics,
benzodiazepines, anticholinergics, antidepressants, calcium channel antagonists,
nonsteroidal anti-inflammatory drugs [NSAIDs], and H1 histamine antagonists) was
compared between those catheterized for urinary retention (n = 34) and those
never catheterized (n = 31). All patients used medication from more than one
class of retention-causing medication. A statistically significant association
with urinary retention occurred for antidopaminergic medications, but not other
drug classes. The total number of classes of retention-causing medications was
not associated with catheterization. These findings question whether urinary
retention need hinder medication use for symptom management at end-of-life.
Tapering of antidopaminergic medications, compared with other drug classes
studied, may be more likely to resolve retention.
PMID- 29336715
TI - Chronic innate immune signaling results in ubiquitination of splicing machinery.
PMID- 29336716
TI - Reactive oxygen species, nitric oxide production and antioxidant gene expression
during development of aerenchyma formation in wheat.
AB - In response to hypoxia, plant roots produce very high levels of nitric oxide.
Recently, it was demonstrated that NO and ethylene both are essential for
development of aerenchyma in wheat roots under hypoxia. Increased NO under
hypoxia correlated with induction of NADPH oxidase gene expression, ROS
production and lipid peroxidation in cortical cells. Tyrosine nitration was
prominent in cells developing aerenchyma suggesting that NO and ROS play a key
role in development of aerenchyma. However, the role of antioxidant genes during
development of aerenchyma is not known, therefore, we checked gene expression of
various antioxidants such as SOD1, AOX1A, APX and MnSOD at different time points
after hypoxia treatment and found that expression of these genes elevated in 2 h
but downregulated in 24 h where development of aerenchyma is prominent. Further,
we found that plants growing under ammonium nutrition displayed delayed
aerenchyma development. Taken together, new insights presented in this short
communication highlighted additional regulatory role of antioxidants gene
expression during aerenchyma development.
PMID- 29336717
TI - PD1 protein expression in tumor infiltrated lymphocytes rather than PDL1 in tumor
cells predicts survival in triple-negative breast cancer.
AB - To determine PD1/PDL1 expression status in triple-negative breast cancer (TNBC)
at both protein and mRNA levels, and to analyze the relationship between their
expression and clinical parameters of the TNBC patients. Immunohistochemistry and
RNAscope were used to semi quantitively evaluate PD1/PDL1 protein and mRNA
expression in 195 TNBC cases on tissue microarrays. Tumor infiltrating lymphocyte
(TILs) abundance was assessed using hematoxylin-eosin staining. Both tumor cells
and TILs expressed PDL1. PDL1 protein and mRNA positivity was 6.7% and 74.4%
respectively in tumor cells, and 31.3% and 50.9% respectively in TILs. PDL1
protein and mRNA expressions had no significant association with patient
prognosis. PD1 protein was only detected in TILs (70.3% positivity). PD1 protein
expression was significantly related to PDL1 expression, higher TIL abundance, Ki
67 index, basal-like subtypes, and distant metastasis. Furthermore, it was
significantly associated with longer disease free survival (P<0.001) and overall
survival (P = 0.004). There was no significant association between PD1 mRNA
expression and clinicopathological characteristics. PD1/PDL1 protein and mRNA
expressions were inconsistent (kappa = 0.705 and 0.061, respectively). PD1
protein expression in TILs, but not PDL1 in tumor cells, was a favorable
prognostic factor in TNBC. PD1/PDL1 mRNA and protein expressions were
inconsistent.
PMID- 29336718
TI - Effect of Irvingia gabonensis on Metabolic Syndrome, Insulin Sensitivity, and
Insulin Secretion.
AB - The aim of this study was to evaluate the effect of Irvingia gabonensis on
metabolic syndrome (MetS), insulin sensitivity, and insulin secretion. A
randomized, double-blind, placebo-controlled clinical trial was performed in 24
patients with MetS in accordance with the International Diabetes Federation
criteria. Twelve patients received I. gabonensis (150 mg) twice a day during 90
days, and 12 patients received placebo. Glucose and insulin concentrations were
measured during a 2-h oral glucose tolerance test. Also, lipid profile,
creatinine, uric acid, and hepatic enzymes were determined. The area under the
curve (AUC) of glucose and insulin, total insulin secretion, first phase of
insulin secretion, and insulin sensitivity were calculated. Data were tested
using non-parametric tests. The Ethics Committee approved the protocol. After I.
gabonensis administration, significant decreases in waist circumference (WC)
(94.0 +/- 8.0 vs. 91.0 +/- 8.2 cm, P < .01), glucose 90' (10.0 +/- 2.5 vs. 8.6 +/
2.7 mmol/L, P < .05), glucose 120' (8.8 +/- 2.4 vs. 7.6 +/- 2.7 mmol/L, P <
.05), triglycerides (2.5 +/- 1.2 vs. 2.0 +/- 1.1 mmol/L, P < .05), very low
density lipoproteins (VLDL) (0.5 +/- 0.2 vs. 0.4 +/- 0.2 mmol/L, P < .05), and
AUC of glucose (694 +/- 142 vs. 629 +/- 172 mmol/L/min, P < .05) were found.
Seven patients (58.3%) of the I. gabonensis group showed remission of MetS and
two patients (16.7%) of the placebo group (P = .045). I. gabonensis lead to
remission of MetS in 58.3% of the patients and significantly decreased WC,
glucose 90', glucose 120', triglycerides, VLDL, and AUC of glucose.
PMID- 29336719
TI - Bidirectional Relationships between Alcohol-Specific Parental Socialization
Behaviors and Adolescent Alcohol Misuse.
AB - BACKGROUND: Although numerous studies have examined parental influence on
adolescent alcohol misuse, few have examined how adolescents impact parental
behavior or the reciprocal nature of parent-adolescent behavior relative to
alcohol misuse. OBJECTIVES: This study assessed bidirectional relationships
between adolescent alcohol misuse and three alcohol-specific parenting behaviors
(substance-specific monitoring, permissive communication messages about alcohol,
and cautionary communication messages about alcohol). METHODS: Data were from
1,645 parent-adolescent dyads drawn from a longitudinal study spanning grades 6
10. A multivariate latent curve model with structured residuals was used to test
study hypotheses. RESULTS: One marginally significant result emerged (increased
alcohol misuse leads to greater substance-specific monitoring) after accounting
for underlying developmental processes. CONCLUSIONS: Though practical
implications are limited based on the results of the study, further directions
for research regarding study design and measurement are provided to more fully
examine dynamic processes between parents and adolescents relative to alcohol
use.
PMID- 29336720
TI - A novel 4-phenyl amino thiourea derivative designed for real-time ratiometric
colorimetric detection of toxic Pb2.
AB - The objective of this study was to develop a ratiometric and colorimetric organic
sensor for Pb2+ detection in environmental samples. A new probe 4-phenyl amino
thiourea (PAT) was designed and synthesized using hydrazine hydrate and phenyl
isothiocyanate as raw materials. After its structure was characterized and
confirmed, its UV-vis spectral property was investigated in detail. PAT possesses
a specifically real-time, ratiometric and colorimetric response to Pb2+ in
dimethyl formamide (DMF)/H2O (v/v = 9:1, pH = 7.0) within 18.0 s. There was
little interference in the presence of some other common metal ions, such as
Fe3+, Cd2+, Zn2+, Mg2+, Cr3+, Ca2+, Ba2+, Sn2+, Na+, Mn2+, Hg2+, and Pb2+. Under
the optimized conditions (DMF/H2O with v/v of 9:1, cPAT = 1.0 * 10-3 mol.L-1, pH
= 7.0), the present sensor PAT was successfully applied for Pb2+ determination in
environmental water samples with satisfied recoveries (83.0%-106.0%) and
analytical precision (<=7.2%). The recognition mechanism was confirmed to form a
stable 1:1 six-member ring complex between the target dye and Pb2+ with a
coordination constant of 4.96 * 104.
PMID- 29336721
TI - Using hydrogen peroxide to prevent antibody disulfide bond reduction during
manufacturing process.
AB - During large-scale monoclonal antibody manufacturing, disulfide bond reduction of
antibodies, which results in generation of low molecule weight species, is
occasionally observed. When this happens, the drug substance does not meet
specifications. Many investigations have been conducted across the
biopharmaceutical industry to identify the root causes, and multiple strategies
have been proposed to mitigate the problem. The reduction is correlated with the
release of cellular reducing components and depletion of dissolved oxygen before,
during, and after harvest. Consequently, these factors can lead to disulfide
reduction over long-duration storage at room temperature prior to Protein A
chromatography. Several strategies have been developed to minimize antibody
reduction, including chemical inhibition of reducing components, maintaining
aeration before and after harvest, and chilling clarified harvest during holding.
Here, we explore the use of hydrogen peroxide in clarified harvest bulk or cell
culture fluid as a strategy to prevent disulfide reduction. A lab-scale study was
performed to demonstrate the effectiveness of hydrogen peroxide in preventing
antibody reduction using multiple IgG molecules. Studies were done to define the
optimal concentration of hydrogen peroxide needed to avoid unnecessary
oxidization of the antibody products. We show that adding a controlled amount of
hydrogen peroxide does not change product quality attributes of the protein.
Since hydrogen peroxide is soluble in aqueous solutions and decomposes into water
and oxygen, there is no additional burden involved in removing it during the
downstream purification steps. Due to its ease of use and minimal product impact,
we demonstrate that hydrogen peroxide treatment is a powerful, simple tool to
quench reducing potential by simply mixing it with harvested cell culture fluid.
PMID- 29336722
TI - Perceptions on technology for volunteer respite care for bedridden elders in
Chile.
AB - PURPOSE: Informal caregivers of bedridden elders need a respite. One form of
obtaining a respite is through volunteers who are contacted by means of
information and communication technology (ICT). METHOD: A qualitative study was
carried out in a low-income district in Santiago, Chile, to learn about how
caregivers of bedridden elders perceive the possibility of using ICT to access
this respite. In-depth interviews were carried out and transcribed verbatim, then
analysed using open coding. Results: The results reveal that caregivers are
willing to receive a volunteer in their home and use ICT to communicate with
them, although a discrepancy exists between the use of devices connected to the
Internet and feature phones. Conclusion: This study concludes that informal
caregivers of bedridden elders have a favourable disposition towards accessing a
respite system by means of ICT based on a peer-to-peer economy.
PMID- 29336723
TI - Chemical characterization and evaluation of the antioxidants in Chaenomeles
fruits by an improved HPLC-TOF/MS coupled to an on-line DPPH-HPLC method.
AB - An improved method based on HPLC-TOF/MS was developed to catalog the antioxidants
in five species of Chaenomeles (Mugua). Forty-four fractions from the Mugua
extracts show appreciable levels of antioxidative activity in scavenging the
stable free-radical 2,2-diphenyl-1-picrylhydrazyl and the hydroxyl radicals.
Twelve major antioxidant's chemical structures are identified. Antioxidant
activities differ between species, but intra-species level of antioxidants,
regardless of their ripeness, are similar. C. sinensis has the highest
antioxidant level. A rigorous quality control procedure was implemented to ensure
accuracy of antioxidant quantification. This improved procedure can be used for
rapid discovery of antioxidants in other plant extracts.
PMID- 29336724
TI - Explicit Awareness does not Modulate Retrograde Interference Effects in Sequence
Learning.
AB - Motor sequences are learned explicitly or implicitly based on conscious awareness
of the sequence. Interference happens when two sequences are learned
successively. Here, we aimed to determine whether implicit and explicit sequence
learning are affected differently by retrograde interference. Young healthy
volunteers participated in either a control or interference group and either an
explicit or implicit learning condition. We used a modified serial reaction time
task to induce sequence learning and control awareness. Results showed that the
overall amount of sequence learning was greater in the explicit condition
compared to implicit. However, sequence learning was equally susceptible to
retrograde interference under either condition. We conclude that although
susceptible to interference, explicit awareness improves overall sequence
learning compared to implicit conditions.
PMID- 29336725
TI - Adaptability of mitosporic stage in Sphaerodes mycoparasitica towards its
mycoparasitic-polyphagous lifestyle.
AB - Sphaerodes mycoparasitica Vuj. is a Fusarium-specific mycoparasite. Some recent
discoveries recognize its biotrophic polyphagous lifestyle as an interesting
biocontrol property against a broad spectrum of mycotoxigenic Fusarium hosts.
Secondary metabolites such as mycotoxins produced by Fusarium spp. may play an
important role in the signaling process, allowing an early mycoparasite-host
recognition. A multiple-paper-disc assay has been conducted to test S.
mycoparasitica hyphal adaptability to filtrates of 12 Fusarium spp. This study
shows that shifts of adapted and nonadapted hyphal migration towards different
Fusarium-host filtrates may partly explain S. mycoparasitica polyphagous
lifestyle, and its adaptability depending on host preference or compatibility. In
terms of host compatibility, the current findings suggest that S. mycoparasitica
tends to prefer native Fusarium hosts more related to its origin and propose that
the mycoparasite could possess diphasic interactions such as biotrophic
attraction and antagonistic-inhibition relationships based on relative radial
growth. This implies that the mycoparasite may use a group of mycotoxins produced
by specific Fusarium spp. as an adaptive selective mechanism that facilitates a
parasite-host recognition and further successful mycoparasitism. In particular,
relative polarity or hydrophilicity/hydrophobicity of mycotoxins may be related
to solubility and absorption properties in hyphae of the mycoparasite. Taken
together, the studies of host compatibility and adaptability depending on host
filtrates will aid in understanding complex mechanisms of S. mycoparasitica, as a
promising model organism for a specific biotrophic mycoparasite to enhance and
improve biocontrol efficacy against Fusaria.
PMID- 29336726
TI - Parallel dual-task processing and task-shielding in older and younger adults:
Behavioral and diffusion model results.
AB - : Background/Study Context: The study investigated the Backward Crosstalk Effect
(BCE) in dual-task situations, that is, the observation that Task 2
characteristics can even influence Task 1 processing. This observation suggests
that the tasks are processed in parallel. Besides determining the existence of a
BCE in a group of older adults, the size of the BCE was compared to that in a
group of younger adults. Importantly, recent studies yielded unclear results.
METHODS: Twenty-four younger and older adults (19-27 and 58-71 years of age,
respectively) performed a dual-task experiment, where Task 1 required a
left/right manual response and Task 2 required a left/right foot response. The
BCE manifests in shorter Task 1 RTs if both responses are given on the same side
(compatible) compared to when they are given on different sides (incompatible).
Data were analyzed by Analyses of Variance and diffusion modeling. RESULTS: Both
age groups clearly exhibited a BCE, and the BCEs were of the same size. Further,
for both age groups, the size of the BCE was similarly modulated by the previous
trial's compatibility status. Diffusion model analyses attribute the BCE to an
increased drift rate in compatible compared to incompatible trials, and also
revealed no age group differences in any of the analyzed parameters. CONCLUSION:
The results point to an aspect of cognition that seems not to show age-related
deteriorations, similar to, for example, n-2 repetition costs in task-switching
situations. Certain response selection-related aspects of task processing are
processed in parallel to the same degree in younger and older adults, and both
age groups are similarly able to shield Task 1 processing from interfering Task 2
processing in a dual-task situation.
PMID- 29336728
TI - The efficacy of cognitive interventions for improving cognitive performance and
academic achievement in children after cancer treatment: A systematic review.
AB - Academic decline has been reported in children after cancer treatment, believed
to be as a result of cognitive impairment. Cognitive interventions may improve
both the present and future outcomes for children after cancer treatment by
improving cognitive and/or academic performance. This review aimed to examine the
efficacy of cognitive interventions in children who had received cancer
treatment. A systematic search of the PsycInfo and PubMed databases was conducted
in May 2015 to identify studies in which cognitive interventions were conducted
with children who had undergone cancer treatment and were under the age of 21.
Cognitive or academic outcomes needed to be reported pre- and post-intervention
to meet the inclusion criteria. Eleven studies were included in this review.
Computerized and home-based cognitive interventions were found to be most
successful at improving cognitive skills. However, few cognitive interventions
assessed academic achievement specifically. Future cognitive intervention
research studies should include measures of academic achievement outcomes,
because academic achievement and cognitive outcomes may differ. Future research
regarding the effectiveness of early, home-based and computerized intervention is
warranted.
PMID- 29336727
TI - Providing services to trafficking survivors: Understanding practices across the
globe.
AB - PURPOSE: Human trafficking is a global issue, with survivors representing all
genders, ages, races, ethnicities, religions, and countries. However, little
research exists that identifies effective practices in supporting survivors of
human trafficking. The research that does exist is Western-centric. To fill this
gap in the literature, the goal of this research was to understand practices used
throughout the globe with adult human trafficking survivors. METHODS: A
qualitative approach was utilized. Providers from 26 countries, across six
different continents, were interviewed to allow for a comprehensive and multi
faceted understanding of practices in working with survivors. RESULTS:
Participants identified utilizing an empowerment-based, survivor, and human life
centered approach to working with survivors, emphasized the importance of
engaging in community level interventions, and highlighted the importance of
government recognition of human trafficking. DISCUSSION: Findings provide
information from the perspective of advocates on best practices in the field that
can be used by agencies to enhance human trafficking programming.
PMID- 29336729
TI - The victim-offender overlap in late adulthood.
AB - This study contributes to the general knowledge of the victim-offender overlap by
determining whether the phenomenon exists among older adults and whether known
correlates of crime and victimization explain the relationship. Cross-sectional
survey data from telephone interviews conducted with individuals 60 years and
older (N = 2,000) residing in Arizona and Florida are used to estimate
confirmatory factor models for both victimization and criminal offending. The
results from a series of multivariate regression models show that victimization
is associated with criminal offending. While factors such as low self-control,
depression, and spending time in commercial drinking establishments partially
attenuate the victimization-crime link, the statistically significant
relationship persists in a multivariate context. Further testing indicates that
the observed findings are robust across measurement and modeling strategies.
Coupled with prior research, the results support the argument that the victim
offender overlap exists (and is difficult to explain) over the life course.
PMID- 29336730
TI - Motor and Visual-spatial Cognition Development in Primary School-Aged Children in
Cameroon and Germany.
AB - It was the main goal of this study to investigate the motor and visual-spatial
development in primary school-aged children in Cameroon and Germany. Thirty-four
children from each country completed a motor test and a mental rotation test. It
was found that children in Cameroon showed a better motor ability (better overall
gross motor score and also on most single items) than children in Germany did.
This can be explained by the early motor stimulation in infancy in Cameroon.
Concerning mental rotation performance, Cameroonian children perform below chance
level. A positive correlation between the overall motor ability and mental
rotation performance could only be analyzed and conducted in the German sample.
Therefore, this study emphasizes the need for the development of culture-fair
cognitive tests.
PMID- 29336731
TI - Lead induces DNA damage and alteration of ALAD and antioxidant genes mRNA
expression in construction site workers.
AB - Oxidative stress and DNA damage are considered as possible mechanisms involved in
lead toxicity. To test this hypothesis, DNA damage and expression variations of
aminolevulinic acid dehydratase (ALAD), superoxide dismutase 2 (SOD2), and 8
oxoguanine DNA glycosylase 2a (OGG1-2a) genes was studied in a cohort of 100
exposed workers and 100 controls with comet assay and real-time polymerse chain
reaction (PCR). Results indicated that increased number of comets was observed in
exposed workers versus controls (p < 0.001). After qPCR analysis, significant
down-regulation in ALAD (p < 0.0001), SOD2 (p < 0.0001), and OGG1-2a (p < 0.0001)
level was observed in exposed workers versus controls. Additionally, a positive
spearmen correlation was observed between ALAD versus SOD2 (r = 0.402**, p <
0.001), ALAD versus OGG1-2a (r = 0.235*, p < 0.05), and SOD2 versus OGG1-2a (r =
0.292*, p < 0.05). This study showed that lead exposure induces DNA damage, which
is accompanied by an elevated intensity of oxidative stress and expression
variation of lead-related gene.
PMID- 29336732
TI - "Some University Lecturers Wear Gay Pride T-shirts. Get Over It!": Denials of
Homophobia and the Reproduction of Heteronormativity in Responses to a Gay-Themed
T-shirt.
AB - This article explores an incident involving a gay pride T-shirt, printed with the
slogan "Some people are gay. Get over it!," that I wore during a university
lecture, and students' predominantly negative responses to it. I use the lens of
modern prejudice research, particularly discursive psychological approaches to
modern prejudice, to interpret the students' responses to a qualitative survey
about their views on the T-shirt. They related strong feelings of upset and
anger, particularly because I had-in their view-implicitly accused them of being
homophobic. They passionately refused this supposed accusation on the grounds
that "everything's equal now" and "gay people are no different from us." I argue
that the ideological themes of cultural heterosexism and compulsory
heterosexuality provide a productive framework for making sense of the students'
responses, as they sanction a rational neoliberal subject who is both non
homophobic and inculcated into heteronormativity.
PMID- 29336733
TI - Impaired Visuospatial Short-Term Memory in Children with ADHD.
AB - Previous studies provide clear evidence that visuospatial memory performance in
children with attention-deficit/hyperactivity disorder (ADHD) is significantly
lower than in typically developing children. In the present study, we
investigated a major cause of their low performance using a spatial span test.
Possibly, inattention resulting from lack of motivation or interest causes their
low performance so that they do not correctly encode targets to be remembered. On
the other hand, a deficit in temporary maintenance per se may cause their low
performance; that is, their inefficient use of rehearsal during a retention
interval may lead to memory traces' fast decay. Results in this study indicated
that children with ADHD could sustain attention during the encoding phase.
Furthermore, their performance at delayed recall was significantly lower than
immediate recall, but delayed recall did not affect typically developing
children's performance. These results provide evidence for the likelihood that a
factor causing children with ADHD difficulty in temporarily maintaining
visuospatial information is fast decay of memory traces as a result of
inefficient use of rehearsal, not inattention in the encoding phase.
PMID- 29336734
TI - The relationship between women's characteristics and herbal medicines use during
pregnancy.
AB - The use of herbal medicines (HM) has been increasing worldwide. This cross
sectional study investigated the prevalence of and characteristics related to use
of HM among 320 pregnant women. Participants were admitted to Mazandaran-based
hospitals' postnatal wards from March to June 2015. Data were collected via a
self-report questionnaire, including herbs used during pregnancy and demographic,
socioeconomic and pregnancy-related factors. Nearly half (48.4%) of the women
reported taking one or more HM during pregnancy. The most frequently used herbs
were Sour orange (30.97%), Peppermint (19.81%) and Borage (19.46%). Most women
(29.20%) were advised by their relatives to take these and did not disclose this
use to their health care providers (50%) because they perceived their use as safe
(39.7%). The use of herbs was greater among pregnant women with upper secondary
level education, living in their own house and from higher socioeconomic classes.
Most of the information sources for women were informal, indicating they were not
knowledgeable about the herbs' safety and efficacy during pregnancy. Health care
providers should be informed about HM and question pregnant women about their use
of HM during pregnancy so that they can advise them about potential side effects
and drug interactions.
PMID- 29336735
TI - Effect of low-cost resistance training on lower-limb strength and balance in
institutionalized seniors.
AB - : Background/Study Context: Given the rapid increase in the aging population
worldwide, fall prevention is of utmost importance. It is essential to establish
an efficient, simple, safe, and low-cost intervention method for reducing the
risk of falls. This study examined the effect of 12 weeks of progressive elastic
resistance training on lower-limb muscle strength and balance in seniors living
in the Rumah Seri Kenangan, social welfare home in Cheras, Malaysia. METHODS: A
total of 51 subjects qualified to take part in this quasi-experimental study.
They were assigned to either the resistance exercise group (n = 26) or control
group (n = 25). The mean age of the 45 participants who completed the program was
70.7 (SD = 6.6). The exercise group met twice per week and performing one to
three sets of 8 to 10 repetitions for each of nine lower-limb elastic resistance
exercises. All exercises were conducted at low to moderate intensities in sitting
or standing positions. The subjects were tested at baseline and 6 and 12 weeks
into the program. RESULTS: The results showed statistically significant
improvements in lower-limb muscle strength as measured by five times sit-to-stand
test (%Delta = 22.6) and dynamic balance quantified by the timed up-and-go test
(%Delta = 18.7), four-square step test (%Delta = 14.67), and step test for the
right (%Delta = 18.36) and left (%Delta = 18.80) legs. No significant changes
were observed in static balance as measured using the tandem stand test (%Delta =
3.25), and one-leg stand test with eyes opened (%Delta = 9.58) and eyes closed
(%Delta = -0.61) after completion of the program. CONCLUSION: The findings
support the feasibility and efficacy of a simple and inexpensive resistance
training program to improve lower-limb muscle strength and dynamic balance among
the institutionalized older adults.
PMID- 29336736
TI - The Emergence and Persistence of Queerness: Conversing Through Visual Culture
Within a Generation.
AB - In this article, the authors explore the work of becoming queer within the
Millennial generation. Collaborative in nature, their investigation turns to
three key popular-culture texts of the 1990s-Will & Grace, Rent, and MTV's Spring
Break-that were central to their then-emerging sense of self. Staged as an
intragenerational conversation, the authors look to create space to unpack the
connections, anecdotal by design, between popular texts and changing ideas of
queer identity and community. Since neither author grew up within the confines of
a gay ghetto-Boystown of Chicago, the Castro of San Francisco, the East Village
of New York City-where they may have encountered and been enamored by the avant
garde queer subcultures so often praised in queer scholarship (for important
reasons), they turn instead to experiences with popular culture that opened up
lessons in becoming gay, in rural and Midwestern locales where queerness operated
and emerged differently.
PMID- 29336737
TI - Handwashing Improvement Project-A Resident Run Success.
PMID- 29336738
TI - Concomitant Fecal Impaction and Perforated Appendicitis in an Autistic Patient.
PMID- 29336739
TI - Nonuterine Lipoleiomyoma.
PMID- 29336740
TI - Primary Synchronous Bilateral Angiosarcoma of the Breast.
PMID- 29336741
TI - Malignant Phyllodes: A Presentation of Two Patients with a Rare Disease.
PMID- 29336742
TI - Small Bowel Obstruction from a 3-cm Gallstone in the Setting of Child-Pugh C
Liver Cirrhosis.
PMID- 29336743
TI - Multiple Mycotic Visceral Artery Aneurysms.
PMID- 29336744
TI - Personal Watercraft Related Injuries-16-Year Experience from a Level I Trauma
Center.
PMID- 29336745
TI - Redo Gracilis Muscle Transposition for Recurrent Complex Pouch-Vaginal Fistula: A
Feasible and Effective Pouch Salvage Surgical Procedure.
PMID- 29336746
TI - Abdominal Splenosis Mimicking Carcinomatosis in a Patient with Acute
Appendicitis.
PMID- 29336747
TI - Traumatic Arteriovesical Fistula from the External Iliac Artery after Gunshot
Wound to the Pelvis.
PMID- 29336748
TI - An Update on the Current Management of Perforated Diverticulitis.
AB - The management of perforated diverticulitis is a challenging aspect of general
surgery. The prevalence of colonic diverticular disease has increased over the
last decade and will continue to increase as the baby boomers add to the elderly
population. Improvements in diagnostic imaging modalities, efforts to maintain
intestinal continuity, and percutaneous drainage procedures now result in several
alternatives when selecting a management strategy for complicated presentations.
Specifically, laparoscopic lavage and resection with primary anastomosis have
emerged as options for treatment of Hinchey III and IV diverticulitis in place of
diversion in the appropriately selected patient. Percutaneous drainage of Hinchey
II diverticulitis in centers equipped with interventional radiology provides
another minimally invasive adjunct. The objective of this paper is to provide an
update on the current management of perforated diverticulitis, with a focus on
the advantages and disadvantages of the surgical options for the treatment of
Hinchey III and IV diverticulitis.
PMID- 29336749
TI - Heroic Measures for an American Hero: Attempting to Save the Life of General
Douglas MacArthur.
AB - General Douglas MacArthur was a towering public figure on an international stage
for the first half of the 20th century. He was healthy throughout his life but
developed a series of medical problems when he entered his 80s. This article
reviews the General's medical care during two separate life-threatening medical
crises that required surgical intervention. The first episode occurred in 1960
when MacArthur presented with renal failure due to an obstructed prostate. Four
years later after his 84th birthday, MacArthur developed bile duct obstruction
from common duct stones. He underwent an uncomplicated cholecystectomy and common
duct exploration but developed variceal bleeding requiring an emergent
splenorenal shunt. His terminal event was precipitated by strangulated bowel in
long-ignored very large inguinal hernias. MacArthur died, despite state-of-the
art surgical intervention, due to renal failure and hepatic coma.
PMID- 29336750
TI - Percutaneous versus Cut-Down Technique for Indwelling Port Placement.
AB - The superiority of surgical cut-down of the cephalic vein versus percutaneous
catheterization of the subclavian vein for the insertion of totally implantable
venous access devices (TIVADs) is debated. To compare the safety and efficacy of
surgical cut-down versus percutaneous placement of TIVADs. This is a single
institution retrospective cohort study of oncologic patients who had TIVADs
implanted by 14 surgeons. Primary outcomes were inability to place TIVAD by the
primary approach and postoperative complications within 30 days. Multivariate
analysis was performed by logistic regression. Secondary outcomes included
operative time. Two hundred and forty-seven (55.9%) percutaneous and 195 (44.1%)
cephalic cut-down patients were identified. The 30-day complication rate was 5.2
per cent: 14 patients (5.7%) in the percutaneous and nine (4.6%) in the cut-down
group. The technique was not a significant predictor of having a 30-day
complication (odds ratio = 0.820; 95% confidence interval 0.342-1.879).
Implantation failure was observed in 16 percutaneous patients (6.5%) and 28 cut
down patients (14.4%) (adjusted odds ratio for cephalic vs cut-down = 2.387; 95%
confidence interval 1.275-4.606). The median operative time for percutaneous
patients was 46 minutes (interquartile range = 35, 59) versus 37.5 minutes
(interquartile range = 30, 49) for cut-down patients(P < 0.0001). Both the
percutaneous and cut-down technique are safe and effective for TIVAD
implantation. Operative times were shorter and the odds of implantation failure
higher for cephalic cut-down. As implantation failure is common, surgeons should
familiarize themselves with both techniques.
PMID- 29336751
TI - Laparoscopic Exploration Can Salvage Recurrent Common Bile Duct Stone after
Cholecystectomy.
AB - Conventionally, patients suffered from recurrent common bile duct (CBD) stone
after cholecystectomy are suggested to be treated with endoscopic retrograde
cholangiopancreaticography. This study was designed to explore the feasibility of
laparoscopic common bile duct exploration (LCBDE) as a salvage procedure for
recurrent CBD calculi after cholecystectomy. A retrospective review was conducted
of data from 65 patients who underwent LCBDE for recurrent CBD calculi after
cholecystectomy from January 2011 to July 2015. LCBDE was successfully carried
out in 61 cases, with a successful rate of 93.8 per cent. Three cases required
open conversion because of serious abdominal adhesion, and one case for
intraoperative bleeding. Postoperative bile leakage occurred in two cases, and
bile peritonitis developed in one case; all these three patients with
complications were fully cured by conservative treatment. A postoperative
retained CBD stone was found in one patient, which was extracted with endoscopic
sphincterotomy. Furthermore, it was found that the mean operative time and length
of postoperative hospital stay were much shorter in primary closure group (n =
49) than in T-tube drainage group (n = 12), and the hospital expense was also
lower in primary closure group. We suggest that LCBDE could be a novel approach
as a salvage procedure for the recurrent CBD stone after cholecystectomy, and we
prefer to intraoperative primary closure of CBD if possible.
PMID- 29336752
TI - External Validation of Velazquez-Gomez Severity Score Index and ATLAS Scores and
the Identification of Risk Factors Associated with Mortality in Clostridium
difficile Infections.
AB - Treatment guidelines for Clostridium difficile infection (CDI) are limited by a
lack of widely accepted clinical prediction tools (CPTs). Two published CPTs, the
Velazquez-Gomez Severity Score Index (VGSSI) and ATLAS scores, were evaluated,
and variables showing the greatest correlation with mortality in patients with
CDI were identified to further develop an objective, mortality-based CPT. A
retrospective review of the charts of 271 hospitalized patients with CDI was
performed. VGSSI and ATLAS scores were assigned. Means and correlations of these
scores with mortality were evaluated. Multivariate logistic regression analysis
was performed on 32 known potential mortality predictor variables. Mortality was
overall strongly associated with VGSSI and ATLAS scores with poor correlation
within the intermediate ranges. Mean scores for nonsurvivors indicated poor
calibration. The variables most associated with mortality were Age, vasopressors,
steroids, creatinine level, and albumin. Although both CPTs revealed the ability
to discriminate patients at greater risk for mortality, precision and overall
calibration were lacking. Five variables were identified which had the greatest
correlation with mortality. Utilization of these variables to enhance or modify
the existing CPTs is suggested as the next step in the development of a useful
and accurate mortality-based CPT for the treatment of CDI.
PMID- 29336753
TI - Randomized Clinical Trial Comparing Low Density versus High Density Meshes in
Patients with Bilateral Inguinal Hernia.
AB - We present a randomized clinical trial to compare postoperative pain,
complications, feeling of a foreign body, and recurrence between heavyweight and
lightweight meshes in patients with bilateral groin hernia. Sixty-seven patients
with bilateral hernia were included in our study. In each patient, the side of
the lightweight mesh was decided by random numbers table. Pain score was measured
by visual analogue scale, on 1st, 3rd, 5th, and 7th postoperative day, and one
year after the surgery. There were no statistically significative differences
between both meshes in postoperative complications. About differences of pain
average, there were statistically significant differences only on the 1st
postoperative day (P <0.01) and the 7th postoperative day (P <0.05). In the
review after a year, there were no statistically significative differences in any
parameter. In our study, we did not find statistically significative differences
between lightweight and heavyweight meshes in postoperative pain, complications,
feeling of a foreign body, and recurrence, except pain on 1st and 7th
postoperative day.
PMID- 29336754
TI - Predictors and Outcomes of Nondiagnostic Ultrasound for Acute Appendicitis in
Children.
AB - Ultrasound assessments of children with possible acute appendicitis (AA) are
often nondiagnostic. We aimed to identify the predictors of nondiagnostic
ultrasound and to investigate the outcomes. A retrospective review was conducted
on children aged 4 to 17 years evaluated in 2013 for AA with ultrasound at a
tertiary hospital pediatric emergency department. Demographics, clinical data,
and outcomes were analyzed. Of 528 children, 194 (36.7%) had diagnostic
ultrasounds and 334 (63.3%) had nondiagnostic ultrasounds. Nondiagnostic
ultrasounds were more common after-hours (7 pm-7 am weekdays and on weekends,
70.7%) than during business hours (7 am-7 pm weekdays; 29.3%). After-hours timing
and female sex were identified as independent predictors of nondiagnostic
ultrasounds (P < 0.05 for both). AA was diagnosed in 35 children with a
nondiagnostic ultrasound (10.5%; P < 0.05). No child who underwent a
nondiagnostic ultrasound was found to have AA with laboratory values of white
blood cell < 11 * 103/uL and c-reactive protein (CRP) < 5 mg/dL. Children with
nondiagnostic ultrasounds have a low likelihood of AA if white blood cell < 11
and CRP < 5. We propose a management algorithm that we hope will help reduce
admissions and decrease the use of computed tomography scans.
PMID- 29336755
TI - Incorporation of Anterior Lumbosacral Spine Exposure into a General Surgical
Practice.
AB - Many spine surgeons enlist the aid of an "access surgeon" to provide anterior
exposure of the lumbosacral spine. We proposed that a single, community hospital
general surgery practice can successfully develop an anterior spine exposure
program with acceptable clinical outcomes. One hundred and forty-three
consecutive anterior exposures were performed between 2008 and 2014. Morbidity
and 30-day mortality were recorded. The effects of American Society of
Anesthesiologists Physical Status classification (ASA class) and number of levels
exposed on length of stay (LOS) and estimated blood loss (EBL) was reported. The
growth of the program during this period was also evaluated. During the six-year
period, there were nine (6.3%) major complications and 17 (11.9%) minor
complications with no 30-day mortality. The mean LOS was similar for one-level
and two-level exposures (3.8 days). Mean LOS was higher in ASA III patients (4.4
days) than ASA I (2.9 days) or ASA II (3.2 days). Mean EBL for one-level
exposures (336.3 mL) was not significantly different than EBL for two-level
exposures (425.9 mL). EBLs in ASA class III patients were greater than in class I
and class II patients. The program began in July of 2008 with a single spine
surgeon and one operation that year. A high of 54 procedures, with seven
different spine surgeons, was recorded in 2013. A single, community hospital
general surgery practice can successfully develop an anterior approach to spine
exposure program with acceptable clinical outcomes and with sustained growth of
the program.
PMID- 29336756
TI - Risk Factors for Elevated Preoperative Alkaline Phosphatase in Patients with
Refractory Secondary Hyperparathyroidism.
AB - Elevated preoperative levels of alkaline phosphatase (ALP) in patients with
refractory secondary hyperparathyroidism are correlated with postoperative
hypocalcemia and mortality. The aim of this study was to identify the predictors
of preoperative ALP in patients with secondary hyperparathyroidism. From April
2012 to December 2015, 220 patients with refractory secondary hyperparathyroidism
undergoing total parathyroidectomy without autotransplantation were reviewed. A
total of 164 patients presented with elevated preoperative ALP. Univariate
analysis showed that patients with elevated ALP were significantly younger. The
elevated ALP group had significantly higher levels of preoperative parathyroid
hormone (PTH), lower preoperative serum calcium, higher preoperative phosphorus,
lower postoperative hypocalcemia, and a longer hospital stay. Logistic regression
analysis showed that elevated preoperative PTH was a significant independent risk
factor for elevated preoperative ALP (P = 0.000), and its value of 1624 pg/mL was
the optimal cutoff point. Factors predictive of elevated preoperative ALP in
patients with secondary hyperparathyroidism include preoperative PTH. Earlier
surgery, aggressive calcium supplementation, and more careful or aggressive
postoperative care for high-risk patients are needed.
PMID- 29336757
TI - Radiofrequency Thermal Ablation Heat Energy Transfer in an Ex-Vivo Model.
AB - Little work has been done to consider the temperature changes and energy transfer
that occur in the tissue outside the vein with ultrasound-guided vein ablation
therapy. In this experiment, a Ex-Vivo model of the human calf was used to
analyze heat transfer and energy degradation in tissue surrounding the vein
during endovascular radiofrequency ablation (RFA). A clinical vein ablation
protocol was used to determine the tissue temperature distribution in 10 per cent
agar gel. Heat energy from the radiofrequency catheter was measured for 140
seconds at fixed points by four thermometer probes placed equidistant radially at
0.0025, 0.005, and 0.01 m away from the RFA catheter. The temperature rose 1.5
degrees C at 0.0025 m, 0.6 degrees C at 0.005 m, and 0.0 degrees C at 0.01 m from
the RFA catheter. There was a clinically insignificant heat transfer at the
distances evaluated, 1.4 +/- 0.2 J/s at 0.0025 m, 0.7 +/- 0.3 J/s at 0.0050 m,
and 0.3 +/- 0.0 J/s at 0.01 m. Heat degradation occurred rapidly: 4.5 +/- 0.5 J
(at 0.0025 m), 4.0 +/- 1.6 J (at 0.0050 m), and 3.9 +/- 3.6 J (at 0.01 m).
Tumescent anesthesia injected one centimeter around the vein would act as a heat
sink to absorb the energy transferred outside the vein to minimize tissue and
nerve damage and will help phlebologists strategize options for minimizing
damage.
PMID- 29336758
TI - Occult Appendiceal Neoplasms in Acute and Chronic Appendicitis: A Single
Institution Experience of 1793 Appendectomies.
AB - The incidence of appendiceal neoplasms may have been underreported in the past.
Patients undergoing incidental appendectomies or appendectomies for chronic
appendicitis may be at higher risk for an incidental appendiceal neoplasm. To
determine the incidence of occult appendiceal neoplasms and identify risk factors
associated with this pathology, a retrospective review of a pathology specimen
database was conducted from November 2007 to December 2011, in a single tertiary
care hospital center. All patients with appendectomies were included for analysis
(n = 1793). Pathology specimens were grouped based on the indication for
appendectomy, and the incidence of appendiceal neoplasms, and patient variables
among the groups were compared using chi2 test and Student's t test. A total of
1793 appendectomy specimens met criteria for evaluation. The total number of
appendiceal neoplasms was 31 (1.7%). There were 14 neoplasms in 1337 (1.0%) cases
of acute appendicitis with 2 in 41 (4.9%) cases of chronic and 15 in 415 (3.6%)
cases, where an incidental appendectomy was performed (P < 0.001). Patients with
carcinoid tumors were significantly younger than patients with noncarcinoid
tumors (P = 0.0001). Indication for operation was the only significant factor for
predicting an appendiceal tumor on final pathology. Patients who undergo interval
or incidental appendectomies may be at higher risk of appendiceal neoplasm
compared with those performed for other indications. Younger patients may be at a
higher risk of occult appendiceal carcinoid neoplasms than other age groups.
Pathologic diagnosis in specific high-risk patient groups may be the only way to
effectively capture these tumors for optimal treatment.
PMID- 29336759
TI - Robotic Rectopexy for Rectal Prolapse in Pediatric Patients.
AB - Rectal prolapse is the protrusion of the rectum out of the anus. Surgical
correction can be accomplished via open and minimally invasive abdominal
approaches, as well as from the perineum. Robotic rectopexy is an option for
minimally invasive treatment of rectal prolapse. There are no studies that have
established the efficacy of robotic rectopexy for rectal prolapse in the
pediatric population. The aim of this study was to review the experience of
robotic rectopexy at a single institution. This is a retrospective review of our
pediatric robotic rectopexy experience from 2012 to 2015. Information was
obtained from chart review of both operative notes and clinic visits. Four
pediatric patients underwent a robotic rectopexy for rectal prolapse from 2012 to
2015. Three patients were male and one was female. The mean age was 15.5 years
(range 13-17). Two patients had rectal prolapse with chronic constipation. One
patient had rectal prolapse from Ehlers Danlos syndrome, and the last had rectal
prolapse after imperforate anus repair as an infant. Three patients received a
bowel preparation. Three patients were completed robotically, and one patient
required conversion to an open procedure. The average postoperative length of
stay was 3.25 days (range 2-4). There were no episodes of recurrent prolapse. Two
patients had improvement in constipation, one had no improvement, and one had no
documented change. Average postoperative follow-up was 11.5 months (range 3-29).
This study was a review of one institution's experience with pediatric robotic
rectopexy. With short-term follow-up, there was no recurrence of prolapse.
Robotic rectopexy provided a safe, reliable, and short-term resolution of rectal
prolapse in pediatric patients.
PMID- 29336760
TI - Cancer Frequency in Retrosternal Goiter.
AB - Retrosternal goiter prevalence is 5 to 40 per cent according to classifications
in goiter series. Goiters with mediastinal extension were reported to be related
with higher cancer rates. In our study, we aimed to investigate whether cancer
incidence increased in retrosternal goiters compared with the cervical ones.
Three hundred and ninety consecutive patients, who had surgery because of
retrosternal goiter in Istanbul University Medical Faculty Department of General
Surgery between 2005 and 2015 were included in the study (Group 1). Control group
included 880 patients who had surgery because of nontoxic multinodular goiter in
the same period (Group 2). Preoperative ultrasonography (USG) was performed to
each patient. Fine-needle aspiration biopsy was performed in suspicious nodules
and results were recorded. Carcinomas in histopathological examination were
classified as intrathorasic and extrathorasic. Diagnostic rates of USG results
were compared with histopathologic cancer results. Papillary carcinoma was
diagnosed in 76 patients with retrosternal goiter (19%) and in 200 patients in
the control group (22%). No statistically significant difference was detected
between groups regarding the tumor rates (P > 0.05). One hundred and forty-four
tumoral foci were detected in 76 patients with papillary carcinoma in
retrosternal goiter patients. Three hundred and seventy tumoral foci were
detected in 200 patients with papillary carcinoma in the control group. In the
retrosternal goiter group, 104 carcinoma lesions of 144 papillary carcinomas were
intrathorasic (72%). No statistically significant difference was detected between
intrathorasic (2.1 +/- 1 cm) and extrathorasic regiones (1.9 +/- 0.8 cm)
regarding the tumor size P > 0.05. When patients with and without cancer in the
retrosternal goiter group were compared regarding familial thyroid cancer
history, radiation to the neck, and cervical adenopathy, no statistically
significant difference was detected. Cancer incidence of retrosternal goiters was
not higher than that of the cervical ones. Yet, cancer foci of retrosternal
goiters were commonly located in the intrathorasic area and were not detected
with USG. Depending on these findings, we suggest that all retrosternal goiters
should be surgically treated.
PMID- 29336761
TI - Lymphatic Permeation Predicts Systemic Recurrence in Combination with Vascular
Involvement in Laparoscopically Resected N0 Colon Cancer.
AB - High-risk patient selection is required in N0 colon cancer. Although a number of
studies have suggested high-risk clinicopathological predictors, most of these
are based on analyses in heterogeous patients in terms of surgical procedures.
Laparoscopic surgery for colon cancer is becoming a standard procedure worldwide
because of its less invasiveness. Accordingly, we aimed to identify bona fide
high-risk factors of recurrence in homogeneous N0 patients who underwent
laparoscopic surgery. Two hundred and twenty-five patients who underwent
laparoscopic curative resection for N0 colon cancer were analyzed.
Clinicopathological parameters were tested for their relation to survival. The 5
year recurrence-free survival rate (RFS) was 96.1 per cent. Lymphatic involvement
(P < 0.001), vascular involvement (P = 0.007), and size of tumor (P = 0.023) were
significantly associated with worse prognosis in the univariate analyses.
Lymphatic involvement was the independent prognostic factor associated with RFS
in the multivariate analysis (P = 0.013). Importantly, lymphatic involvement
predicts detrimental prognosis only when vascular involvement is present. The RFS
of the patients with both lymphatic and vascular involvement was 88.9 per cent,
whereas it was 100 per cent in the counterpart. Differentiation, vascular
involvement preoperative carcinoembryonic antigen, and CA 19-9 levels were
significantly associated with lymphatic involvement in a multivariate logistic
regression analyses. The present study concludes that lymphatic involvement in
the presence of vascular involvement may be a high risk for systemic recurrence
in the laparoscopically resected N0 colon cancer.
PMID- 29336762
TI - R A Cowley, the "Golden Hour," the "Momentary Pause," and the "Third Space".
AB - R Adams Cowley (1917-1991), the Baltimore thoracic and trauma surgeon, was an
outstanding politician and promoter of emergency medical services. His skills
included the effective use of language, for example, identifying the critical
time immediately after injury as a "golden hour," and describing shock as a
"momentary pause in the act of death." Conversely, Cowley avoided the tendency of
some contemporaries to justify massive crystalloid infusion by invoking a "third
space." Cowley is often assumed to have originated the first two phrases, but, in
fact, their histories go back at least to the 19th century and illustrate the
development of surgical science. The "third space" is often assumed to have
originated with Cowley's contemporary, Tom Shires (1925-2007), but, in fact,
neither of them used the phrase to describe Shires' controversial theories about
an extracellular fluid deficit after trauma. Reviewing the actual etymology of
these terms may help clarify the history of the underlying scientific ideas and
enable more effective communication in the future.
PMID- 29336763
TI - Methicillin-Resistant Staphylococcus aureus in a Trauma Population: Does
Decolonization Prevent Infection?
AB - The purpose of this study was to determine if a decolonization regimen reduces
the frequency of methicillin-resistant Staphylococcus aureus (MRSA) infections
and if colonization isolates are genetically related to subsequent infectious
strains. Trauma patients admitted to the intensive care unit with positive MRSA
nasal swabs were randomized to either daily chlorhexidine gluconate (CHG) baths
and mupirocin (MUP) ointment to the nares or soap and water baths and placebo
ointment for five days. Nasal swabs performed at the end of treatment and
invasive MRSA infections during the remaining hospitalization were compared with
the original nasal isolate via polymerase chain reaction for genetic relatedness
as well as CHG and MUP resistance genes. Six hundred and seventy-eight intensive
care unit admissions were screened, and 92 (13.6%) had positive (+) MRSA nasal
swabs over a 22-month period ending in 3/2014. After the five day treatment
period, there were 13 (59.1%) +MRSA second nasal swabs for CHG + MUP and 9 (90%)
for soap and water baths and placebo, P = 0.114. No isolates tested positive for
the MUP or CHG resistance genes mupA and qacA/B but 7 of 20 (35%) contained smr.
There were seven (31.8%) MRSA infections in the CHG group and six (60%) for soap,
P = 0.244. All 13 patients with MRSA infections had the same MRSA isolate present
in the original nasal swab. There was no difference in all-cause Gram-negative or
positive infections for CHG versus soap, 12 (54.5%) versus 7 (70%), P = 0.467.
CHG + MUP are ineffective in eradicating MRSA from the anterior nares but may
reduce the incidence of infection. Subsequent invasive MRSA infections are
typically caused by the endogenous colonization strain.
PMID- 29336764
TI - Mode of Transport and Clinical Outcome in Rural Trauma: A Helicopter versus
Ambulance Comparison.
AB - Helicopter Emergency Medical Services (HEMS) is presumably an effective way of
patient transport in rural trauma, yet the literature addressing its
effectiveness is scarce. In this study, we compared the clinical outcome of rural
trauma patients between Ground Emergency Medical Services (GEMS) and HEMS
transportation from the beginning of 2006 to the end of 2012. Focus was placed on
identifying factors associated with survival to discharge in these patients. Over
the seven-year study period, 4492 patients met the inclusion criteria with 2414
patients (54%) being transferred by GEMS and 2078 patients (46%) being
transferred by HEMS. In comparison with GEMS, patients transferred by HEMS were
younger men who were admitted with a higher mean Injury Severity Score and a
lower mean Glasgow Coma Score (all Ps < 0.0001). HEMS patients were more
frequently intubated before arrival at the trauma center (32% vs 9%, P < 0.0001)
and were more frequently transferred to the operating room from the emergency
department (11% vs 5%, P < 0.0001). In multivariate analysis, transfer by HEMS
was associated with a significant increase in survival to discharge (odds ratio:
1.57, 95% confidence interval: 1.03-2.40, P = 0.036). Blunt injury, no
intubation, and Glasgow Coma Score >8 were also associated with significantly
improved odds of survival to discharge (all P < 0.0001). These findings show that
although patients transferred by HEMS arrived in less favorable clinical
conditions, HEMS transfer was associated with significantly higher odds of
survival in rural trauma.
PMID- 29336765
TI - Robotic Inguinal Hernia Repair.
AB - Laparoscopic inguinal hernia repair has certain advantages over open repair
including less pain and earlier return to normal activity. Concurrent robotic
inguinal hernia repair at the time of prostatectomy has been shown to have a
lower recurrence rate than open repair. Robotic surgery adds high definition
visualization and articulating instruments which enhances dexterity that makes
laparoscopic hernia repair more refined. A series of robotic, laparoscopic,
inguinal hernia repairs by a single surgeon with an extensive laparoscopic hernia
experience at a single institution was undertaken to determine the role of
robotic laparoscopic inguinal hernia repair in minimally invasive surgery. Five
hundred forty-two laparoscopic inguinal hernia operations were performed from
April 2012 through December 2015. There were 154 cases of robotic transabdominal
preperitoneal procedures done during that time. Hospital records and follow-up
care were prospectively reviewed and data collected for age, sex, American
Society of Anesthesia class, and operative time. Follow-up was done at 2, 8, and
16 weeks after surgery. All patients consented for the study. Ninety percent of
the patients were male. Age averaged 57.04 years with a range of 21 to 85 years.
American Society of Anesthesia averaged 2.01 with comorbidities of hypertension,
hypercholesterolemia, and gastroesophageal reflux disease being the most common.
Body mass index was between 19 and 31.6, averaging 24.34. Twenty-five patients
(16%) had an umbilical hernia repair done concomitantly. Operating room time
ranged from 25 to 140 minutes with an average of 63.6 minutes decreased as
experience increased. One patient with a large, left scrotal hernia was converted
to open; one patient developed perforated sigmoid diverticulitis seven days
postop and case #5 recurred indirectly after a direct hernia repair. Four
patients required prolonged postoperative Foley catheterization. Robotic inguinal
hernia repair is safe and effective. Operating room time was longer than standard
laparoscopic herniorrhaphy but decreased with experience. A single-port platform
may have use in patients with umbilical hernias, 16 per cent, and will need to be
studied.
PMID- 29336766
TI - The Implications of Transfer to an Acute Care Surgical Tertiary Service.
AB - Tertiary hospitals are increasingly called on by smaller hospitals and free
standing emergency rooms (ERs) to provide surgical care for complex patients.
This study assesses patients transferred to an acute care surgery service. The ER
and transfer center logs, as well as billing data, were reviewed for 12 months
for all cases evaluated by acute care surgery. The charts were reviewed for
demographics, comorbidities, and outcomes. A total of 111 transferred patients
with complete data were identified, with 59 transferred from another hospital and
52 from a free-standing ER. The hospital transfer patients were older with more
comorbidities, had a longer length of stay, and were more likely discharged to
skilled care. There was no difference in the percent of patients requiring a
procedure; however, significantly more procedures in the hospital transfer group
were done by nonsurgical specialties Better infrastructure to monitor the impact
of hospital transfers is warranted in the setting of the complex patient
population transferred to tertiary hospitals.
PMID- 29336767
TI - Surgery for Acromioclavicular Dislocation: Factors Affecting Functional Recovery.
AB - The objective of the study is to compare the clinical outcomes of two different
interventions for Rockwood type III (or above) acromioclavicular dislocation and
study the factors influencing postoperative functional recovery. A total of 60
patients with Rockwood type III (or above) acromioclavicular dislocation were
included in the study. Patients were divided into two groups based on the
surgical intervention: Clavicular Hook Plate Fixation (Group A) and EndoButton
technique of Coracoclavicular Ligament Reconstruction (Group B). Constant
shoulder score was employed for the assessment of functional recovery before and
after the surgery. Statistical analysis was performed in terms of age, gender,
obesity (body mass index), Constant shoulder score, compliance of rehabilitation
guidance, and the amount of reduction loss. The Constant score was significantly
improved after surgery (P < 0.05). The score was better in Group B compared with
Group A in the sixth month after surgery (P < 0.05), but showed no significant
difference in the fifteenth month. Compliance with rehabilitation guidance
significantly affected the values of the Constant score after the surgery (P <
0.05). Clavicular Hook Plate and EndoButton technique both are effective ways to
treat Rockwood type III (or above) acromioclavicular dislocation. However,
EndoButton technique is more effective for early functional recovery. Patients'
compliance with rehabilitation guidance is critical for the functional recovery
after surgery.
PMID- 29336768
TI - Is Routine Continuous EEG for Traumatic Brain Injury Beneficial?
AB - Severe traumatic brain injury (TBI) is associated with increased risk for early
clinical and subclinical seizures. The use of continuous electroencephalography
(cEEG) monitoring after TBI allows for identification and treatment of seizures
that may otherwise occur undetected. Benefits of "routine" cEEG after TBI remain
controversial. We examined the rate of subclinical seizures identified by cEEG in
TBI patients admitted to a Level I trauma center. We analyzed a cohort of trauma
patients with moderate to severe TBI (head Abbreviated Injury Score >=3) who
received cEEG within seven days of admission between October 2011 and May 2015.
Demographics, clinical data, injury severity, and costs were recorded. Clinical
characteristics were compared between those with and without seizures as
identified by cEEG. A total of 106 TBI patients with moderate to severe TBI
received a cEEG during the study period. Most were male (74%) with a mean age of
55 years. Subclinical seizures were identified by cEEG in only 3.8 per cent of
patients. Ninety-three per cent were on antiseizure prophylaxis at the time of
cEEG. Patients who had subclinical seizures were significantly older than their
counterparts (80 vs 54 years, P = 0.03) with a higher mean head Abbreviated
Injury Score (5.0 vs 4.0, P = 0.01). Mortality and intensive care unit stay were
similar in both groups. Of all TBI patients who were monitored with cEEG,
seizures were identified in only 3.8 per cent. Seizures were more likely to occur
in older patients with severe head injury. Given the high cost of routine cEEG
and the low incidence of subclinical seizures, we recommend cEEG monitoring only
when clinically indicated.
PMID- 29336769
TI - Processes of Health Care Delivery, Education, and Provider Satisfaction in Acute
Care Surgery: A Systematic Review.
AB - In recent years, significant workload, high acuity, and complexity of emergency
general surgery conditions have led hospitals to replace the traditional on-call
model with dedicated acute care surgery (ACS) service models. A systematic search
of Ovid, EMBASE, and MEDLINE was undertaken to examine the impact of ACS services
on health-care delivery processes and cost, education, and provider satisfaction.
From 1827 papers, reviewers identified 22 studies that met inclusion criteria and
subsequently used The Evidence-Based Practice for Improving Quality method and
Newcastle-Ottawa Scale to score quality and level of evidence. Most studies found
an increase in daytime operating, improved patient transit from emergency
department to operating room to home, and decreased length of stay. Higher and
more diverse case volumes improved resident education and operative experience.
ACS services enhanced the educational experience of residents on subspecialty
services by offloading emergency work from those services. Finally, surgeons
generally felt that ACS services improved job satisfaction, productivity, and
billing. The ACS model has demonstrated improvement in timeliness of care,
diversified case mix, decreased costs, improved trainee learning, and increased
surgeon job satisfaction.
PMID- 29336770
TI - Limit Crystalloid Resuscitation after Traumatic Brain Injury.
AB - Patients with traumatic brain injury (TBI) are often resuscitated with
crystalloids in the emergency department (ED) to maintain cerebral perfusion. The
purpose of this study was to evaluate whether crystalloid resuscitation volume
impacts mortality in TBI patients. This was a retrospective study of trauma
patients with head abbreviated injury scale score >=2, who received crystalloids
during ED resuscitation between 2004 and 2013. Clinical characteristics and
volume of crystalloids received in the ED were collected. Patients who received
<2 L of crystalloids were categorized as low volume (LOW), whereas those who
received >=2 L were considered high volume (HIGH). Mortality and outcomes were
compared. Multivariable regression analysis was used to determine the odds of
mortality while controlling for confounders. Over 10 years, 875 patients met
inclusion criteria. Overall mortality was 12.5 per cent. Seven hundred and forty
two (85%) were in the LOW cohort and 133 (15%) in the HIGH cohort. Gender and age
were similar between the groups. The HIGH cohort had lower admission systolic
blood pressure (128 vs 138 mm Hg, P = 0.001), lower Glasgow coma scale score (10
vs 12, P < 0.001), higher head abbreviated injury scale (3.8 vs 3.3, P < 0.001),
and higher injury severity score (25 vs 18, P < 0.001). The LOW group had a lower
unadjusted mortality (10 vs 26%, P < 0.001). Multivariable analysis adjusting for
confounders demonstrated that those resuscitated with >=2 L of crystalloids had
increased odds of mortality (adjusted odds ratio 2.25, P = 0.005). Higher volume
crystalloid resuscitation after TBI is associated with increased mortality, thus
limited resuscitation for TBI patients may be indicated.
PMID- 29336771
TI - Surgical and Endovascular Management of Patients with Chronic Mesenteric
Ischemia: A Single Center Experience.
AB - Chronic mesenteric ischemia is a rare intestinal disorder, with a potential
evolution toward intestinal infraction. The choice of the appropriate treatment
is currently the most crucial issue in the management of patients with chronic
mesenteric ischemia. We describe our experience with 16 cases, and we discuss the
current diagnostic and therapeutic approaches. A retrospective review of the
clinical records was performed, and demographic, clinical, therapeutic, and
prognostic data were collected. Six patients were females (37%), and the mean age
was 62 years. Postprandial pain was present in all the cases, whereas sitophobia
and weight loss were detected in 87 per cent of them. Eight patients were treated
with open surgery; no perioperative deaths or relevant complications occurred.
One patient had a restenosis of the celiac trunk and superior mesenteric artery
10 months after surgery. No deaths or relevant complications occurred in the
remaining patients, who underwent an endovascular procedure. One patient
presented a restenosis distal to the vascular stent, whereas two patients died
due to comorbidities. The low rates of postoperative morbidity, mortality, and
restenosis obtained suggest that surgical or endovascular correction of chronic
mesenteric ischemia is satisfactory when performed by experienced surgeons, with
an adequate selection of the patients.
PMID- 29336772
TI - tPA/DNase for Complicated Parapneumonic Effusions and Empyemas.
PMID- 29336773
TI - Outcomes of Elderly Patients Undergoing Elective Abdominal Surgery.
PMID- 29336774
TI - Altered cortical thickness and attentional deficits in adolescent girls and women
with bulimia nervosa.
AB - BACKGROUND: Frontostriatal and frontoparietal abnormalities likely contribute to
deficits in control and attentional processes in individuals with bulimia nervosa
and to the persistence of dysregulated eating across development. This study
assessed these processes and cortical thickness in a large sample of adolescent
girls and women with bulimia nervosa compared with healthy controls. METHODS: We
collected anatomical MRI data from adolescent girls and women (ages 12-38 yr)
with full or subthreshold bulimia nervosa and age-matched healthy controls who
also completed the Conners Continuous Performance Test-II (CPT-II). Groups were
compared on task performance and cortical thickness. Mediation analyses explored
associations among cortical thickness, CPT-II variables, bulimia nervosa symptoms
and age. RESULTS: We included 60 girls and women with bulimia nervosa and 54
controls in the analyses. Compared with healthy participants, those with bulimia
nervosa showed increased impulsivity and inattention on the CPT-II, along with
reduced thickness of the right pars triangularis, right superior parietal and
left dorsal posterior cingulate cortices. In the bulimia nervosa group,
exploratory analyses revealed that binge eating frequency correlated inversely
with cortical thickness of frontoparietal and insular regions and that reduced
frontoparietal thickness mediated the association between age and increased
symptom severity and inattention. Binge eating frequency also mediated the
association between age and lower prefrontal cortical thickness. LIMITATIONS:
These findings are applicable to only girls and women with bulimia nervosa, and
our cross-sectional design precludes understanding of whether cortical thickness
alterations precede or result from bulimia nervosa symptoms. CONCLUSION:
Structural abnormalities in the frontoparietal and posterior cingulate regions
comprising circuits that support control and attentional processes should be
investigated as potential contributors to the maintenance of bulimia nervosa and
useful targets for novel interventions.
PMID- 29336775
TI - Neural correlates of emotional action control in anger-prone women with
borderline personality disorder.
AB - BACKGROUND: Difficulty in controlling emotional impulses is a crucial component
of borderline personality disorder (BPD) that often leads to destructive,
impulsive behaviours against others. In line with recent findings in aggressive
individuals, deficits in prefrontal amygdala coupling during emotional action
control may account for these symptoms. METHODS: To study the neurobiological
correlates of altered emotional action control in individuals with BPD, we asked
medication-free, anger-prone, female patients with BPD and age- and intelligence
matched healthy women to take part in an approach-avoidance task while lying in
an MRI scanner. The task required controlling fast behavioural tendencies to
approach happy and avoid angry faces. Additionally, before the task we collected
saliva testosterone and self-reported information on tendencies to act out anger
and correlated this with behavioural and functional MRI (fMRI) data. RESULTS: We
included 30 patients and 28 controls in our analysis. Patients with BPD reported
increased tendencies to act out anger and were faster in approaching than
avoiding angry faces than with healthy women, suggesting deficits in emotional
action control in women with BPD. On a neural level, controlling fast emotional
action tendencies was associated with enhanced activation in the antero- and
dorsolateral prefrontal cortex across groups. Healthy women showed a negative
coupling between the left dorsolateral prefrontal cortex and right amygdala,
whereas this was absent in patients with BPD. LIMITATIONS: Specificity of results
to BPD and sex differences remain unknown owing to the lack of clinical control
groups and male participants. CONCLUSION: The results indicate reduced lateral
prefrontal-amygdala communication during emotional action control in anger-prone
women with BPD. The findings provide a possible neural mechanism underlying
difficulties with controlling emotional impulses in patients with BPD.
PMID- 29336776
TI - Pharmacokinetics and dose individualization of ceftriaxone in a hepatically
impaired, critically-ill patient receiving continuous venovenous hemofiltration.
PMID- 29336777
TI - Presence of apoptosis distinguishes primary central nervous system lymphoma from
glioblastoma during intraoperative consultation.
AB - AIM: To evaluate the overlapping and distinguishing cytologic features of primary
central nervous system lymphoma (PCNSL), diffuse large B-cell lymphoma, and
glioblastoma (GM) in frozen sections and squash smear slides. MATERIALS AND
METHODS: Intraoperative frozen sections and squash smear slides from PCNSL (N =
63) and GM (N = 122) patients diagnosed from 2005 to 2015 were retrieved from
pathology records. Overlapping and distinguishing histologic features were
examined and statistically analyzed. RESULTS: Necrosis and moderate nuclear size
variation were common features of PCNSL and GM. PCNSL characteristically showed
apoptosis, lack of a fibrillary background, monotonous nuclei, scant cytoplasm,
lack of microvascular proliferation, and presence of perivascular cuffing.
Multivariate analysis revealed that presence of apoptosis was the most powerful
predictive parameter for the diagnosis of PCNSL. CONCLUSION: The presence of
apoptosis was effective for the intraoperative diagnosis of PCNSL compared to
GM.?.
PMID- 29336779
TI - Prophylactic thyroidectomies in MEN2 syndrome: Management and outcomes.
AB - AIM OF THE STUDY: The aim of the study was to evaluate the outcomes of
prophylactic thyroidectomies performed in an academic setting in the context of
multiple endocrine neoplasia type 2 (MEN2) syndrome. METHODS: A chart review of
patients <18years old who underwent prophylactic thyroidectomy for a MEN2
syndrome at a children's hospital between 2006 and 2015 was performed. MAIN
RESULTS: The study included 21 patients (57% female) with a mean age of 6.2+/
2.5years. All patients were asymptomatic at first evaluation. Nineteen had MEN2A
syndrome with RET proto-oncogene mutations identified. The remaining two were RET
negative with familial medullary thyroid cancer (FMTC). One patient had a
concomitant Hirschsprung disease. Of the 11 patients who had RET proto-oncogene
mutations ranked as Moderate Risk for medullary thyroid cancer (MTC) (American
Thyroid Association), one had a microcarcinoma on the resected specimen, and the
others had C-Cell Hyperplasia. Among the 8 patients who had RET proto-oncogene
mutations ranked as High Risk level for MTC, all had microcarcinoma. Of the nine
patients with microcarcinoma, three underwent surgery after 5years of age. No
microcarcinoma exceeded 6mm. There were no permanent complications. Six patients
experienced transient hypocalcemia, of which only one was symptomatic. No
patients had lymph node involvement, and no recurrence was noted during the
follow-up period. CONCLUSIONS: Of 21 children with familial thyroid cancer
syndrome who underwent a prophylactic thyroidectomy, nine had microcarcinoma.
This study highlights the need for a complete familial history, including FMTC
history and mandatory preventive surgical approach. LEVEL OF EVIDENCE: III.
PMID- 29336778
TI - Damage-induced reactive oxygen species regulate vimentin and dynamic collagen
based projections to mediate wound repair.
AB - Tissue injury leads to early wound-associated reactive oxygen species (ROS)
production that mediate tissue regeneration. To identify mechanisms that function
downstream of redox signals that modulate regeneration, a vimentin reporter of
mesenchymal cells was generated by driving GFP from the vimentin promoter in
zebrafish. Early redox signaling mediated vimentin reporter activity at the wound
margin. Moreover, both ROS and vimentin were necessary for collagen production
and reorganization into projections at the leading edge of the wound. Second
harmonic generation time-lapse imaging revealed that the collagen projections
were associated with dynamic epithelial extensions at the wound edge during wound
repair. Perturbing collagen organization by burn wound disrupted epithelial
projections and subsequent wound healing. Taken together our findings suggest
that ROS and vimentin integrate early wound signals to orchestrate the formation
of collagen-based projections that guide regenerative growth during efficient
wound repair.
PMID- 29336780
TI - Advances in non-contrast quiescent-interval slice-selective (QISS) magnetic
resonance angiography.
AB - There is a pressing clinical need to develop accurate, efficient non-contrast
magnetic resonance angiography (NC-MRA) techniques. Our efforts in the field have
focused on a novel non-subtractive technique called quiescent-interval slice
selective (QISS) MRA. Compared with other NC-MRA techniques, QISS has the
advantage of being more accurate while enabling a simpler and more efficient
workflow. The original implementation, which uses electrocardiogram (ECG) gating
and a Cartesian k-space trajectory, is a reliable technique for the evaluation of
peripheral arterial disease (PAD). Recent advances in QISS technology include the
use of a radial k-space trajectory, which facilitates rapid imaging of the
coronary, renal, and pulmonary arteries as well as other vascular beds, and
ungated ("UnQISS") acquisitions for PAD.
PMID- 29336781
TI - Corrigendum to "Osteopontin promotes collagen I synthesis in hepatic stellate
cells by miRNA-129-5p inhibition" [Exp. Cell Res. 362(2) (2018) 343-348].
PMID- 29336782
TI - Loss of GPNMB Causes Autosomal-Recessive Amyloidosis Cutis Dyschromica in Humans.
AB - Amyloidosis cutis dyschromica (ACD) is a distinct form of primary cutaneous
amyloidosis characterized by generalized hyperpigmentation mottled with small
hypopigmented macules on the trunks and limbs. Affected families and sporadic
case subjects have been reported predominantly in East and Southeast Asian
ethnicities; however, the genetic cause has not been elucidated. We report here
that the compound heterozygosity or homozygosity of GPNMB truncating alleles is
the cause of autosomal-recessive ACD. Six nonsense or frameshift mutations were
identified in nine individuals diagnosed with ACD. Immunofluorescence analysis of
skin biopsies showed that GPNMB is expressed in all epidermal cells, with the
highest staining observed in melanocytes. GPNMB staining is significantly reduced
in the lesional skin of affected individuals. Hyperpigmented lesions exhibited
significantly increased amounts of DNA/keratin-positive amyloid deposits in the
papillary dermis and infiltrating macrophages compared with hypo- or depigmented
macules. Depigmentation of the lesions was attributable to loss of melanocytes.
Intracytoplasmic fibrillary aggregates were observed in keratinocytes scattered
in the lesional epidermis. Thus, our analysis indicates that loss of GPNMB, which
has been implicated in melanosome formation, autophagy, phagocytosis, tissue
repair, and negative regulation of inflammation, underlies autosomal-recessive
ACD and provides insights into the etiology of amyloidosis and pigment
dyschromia.
PMID- 29336783
TI - Bronchiectasis is highly prevalent in anti-MPO ANCA-associated vasculitis and is
associated with a distinct disease presentation.
AB - OBJECTIVES: To assess the prevalence of bronchiectasis in a Western cohort with
ANCA-positive granulomatosis with polyangiitis (GPA) or microscopic polyangiitis
(MPA) and its correlations with disease presentation and outcome. METHODS:
Retrospective study of ANCA-associated vasculitis (AAV) patients followed at
Nantes University Hospital (2005-2015). Clinical, biological, and follow-up data
were collected through chart review. Two experienced radiologists blinded to the
clinical data interpreted chest high-resolution CTs according to the Feischner
Society criteria. RESULTS: Fifty-eight patients were included: 30 had MPA (51.7%)
and 28 had GPA (48.3%). The median age at AAV diagnosis was 65.5 years. Anti-MPO
ANCA and anti-PR3-ANCA were present in 39 (67.2%) and 19 (32.8%) patients,
respectively. Overall, bronchiectasis was found in 22 patients (37.9%), all of
whom had anti-MPO ANCA. In multivariate analysis, bronchiectasis was
independently associated with anti-MPO-ANCA, female gender and age at AAV
diagnosis. Furthermore, anti-MPO ANCA patients with bronchiectasis had more
frequent peripheral nerve involvement (54.5 vs. 17.6%, p = 0.019) and less
frequent renal involvement than those without bronchiectasis (40.9% vs. 82.3%, p
= 0.009). Disease course, survival and risk of severe pulmonary infection were
similar in patients with and without bronchiectasis on chest CT. CONCLUSIONS:
This study shows that bronchiectasis is a highly prevalent pre-existing
respiratory condition in Caucasian patients with anti-MPO AAV. This subset of
patients exhibits a distinct presentation. Further studies are needed to confirm
these findings and clarify the clinical implications of this association. Whether
the respiratory tract could be the site of initiation of anti-MPO auto-immunity
remains to be investigated.
PMID- 29336784
TI - Reflections on the utility of excess bases as a marker in the prognosis of chest
trauma in the geriatric population.
PMID- 29336785
TI - The erector spinae plane block in 4 cases of video-assisted thoracic surgery.
AB - Multimodal anaesthesia, combining epidural catheter and general anaesthesia, is a
common technique in thoracic surgery, however, epidural catheter placement is not
always possible. Recently, erector spinae plane block has been described, which
provides analgesia like that of the epidural block, although unilateral, and
which has been used in various procedures at thoracic level. At present, there
are no studies comparing the efficacy or safety of this block with those commonly
used in thoracic surgery. However, its safety profile and contraindications seem
different from those of the epidural catheter, since its placement is done under
ultrasound view, the needle introduction is done in plane and the ultrasound
target, the transverse process, is easily identifiable and is relatively remote
from major neural or vascular structures and the pleura. Unlike other blockages
made by anatomical references, erector spinae plane block can be done with the
patient in different positions. We describe our experience with erector spinae
plane block as part of a multimodal anaesthetic approach in thoracic surgery.
PMID- 29336786
TI - A Possible Role of Takotsubo Cardiomyopathy in Ventricular Fibrillation During
Delirium Tremens: A Case Report and Literature Review.
PMID- 29336787
TI - Clinical Severity Alone Does Not Determine Disposition Decisions for Patients in
the Emergency Department with Suicide Risk.
AB - BACKGROUND: Boarding of patients with suicide risk in emergency departments (EDs)
negatively affects both patients and society. Factors other than clinical
severity may frequently preclude safe outpatient dispositions among suicidal
patients boarding for psychiatric admission in the ED. OBJECTIVE: To determine
the extent to which nonclinical factors preclude safe outpatient discharge from
the ED among patients boarding for psychiatric admission based on suicide risk.
METHODS: A survey regarding the importance of 13 clinical and 19 nonclinical
barriers to safe outpatient disposition was administered in the ED to 40 adults
who were determined by psychiatrists to require inpatient level of psychiatric
care due to suicide risk. A second survey regarding whether addressing the
nonclinical factors would have enabled a safe outpatient disposition in each case
was administered to the psychiatrists who evaluated each patient participant.
RESULTS: Out of 40 patient participants, 39 cited at least one nonclinical factor
that could have enabled a safe outpatient disposition had it been correctable in
the ED. According to the psychiatrists who made the decision to hospitalize, 10
(25%) of the patient participants could have been discharged had social support
become available. CONCLUSION: Both clinical and nonclinical factors affect
disposition from the ED after an evaluation for suicide risk. Attention to
nonclinical factors should be considered in programmatic efforts to reduce ED
boarding of patients with suicide risk.
PMID- 29336788
TI - Grey Wolf based control for speed ripple reduction at low speed operation of PMSM
drives.
AB - Speed ripple at low speed-high torque operation of Permanent Magnet Synchronous
Machine (PMSM) drives is considered as one of the major issues to be treated. The
presented work proposes an efficient PMSM speed controller based on Grey Wolf
(GW) algorithm to ensure a high-performance control for speed ripple reduction at
low speed operation. The main idea of the proposed control algorithm is to
propose a specific objective function in order to incorporate the advantage of
fast optimization process of the GW optimizer. The role of GW optimizer is to
find the optimal input controls that satisfy the speed tracking requirements. The
synthesis methodology of the proposed control algorithm is detailed and the
feasibility and performances of the proposed speed controller is confirmed by
simulation and experimental results. The GW algorithm is a model-free controller
and the parameters of its objective function are easy to be tuned. The GW
controller is compared to PI one on real test bench. Then, the superiority of the
first algorithm is highlighted.
PMID- 29336789
TI - Actuator stiction compensation via variable amplitude pulses.
AB - A novel model free stiction compensation scheme is developed which eliminates the
oscillations and also reduces valve movement, allowing good setpoint tracking and
disturbance rejection. Pulses with varying amplitude are added to the controller
output to overcome stiction and when the error becomes smaller than a specified
limit, the compensation ceases and remains in a standby mode. The compensation re
starts as soon as the error exceeds the user specified threshold. The ability to
cope with uncertainty in friction is a feature achieved by the use of pulses of
varying amplitude. The algorithm has been evaluated via simulation and by
application on an industrial DCS system interfaced to a pilot scale process with
features identical to those found in industry including a valve positioner.
PMID- 29336790
TI - A multiple kernel classification approach based on a Quadratic Successive
Geometric Segmentation methodology with a fault diagnosis case.
AB - This work presents a new approach for solving classification and learning
problems. The Successive Geometric Segmentation technique is applied to
encapsulate large datasets by using a series of Oriented Bounding Hyper Box
(OBHBs). Each OBHB is obtained through linear separation analysis and each one
represents a specific region in a pattern's solution space. Also, each OBHB can
be seen as a data abstraction layer and be considered as an individual Kernel.
Thus, it is possible by applying a quadratic discriminant function, to assemble a
set of nonlinear surfaces separating each desirable pattern. This approach allows
working with large datasets using high speed linear analysis tools and yet
providing a very accurate non-linear classifier as final result. The methodology
was tested using the UCI Machine Learning repository and a Power Transformer
Fault Diagnosis real scenario problem. The results were compared with different
approaches provided by literature and, finally, the potential and further
applications of the methodology were also discussed.
PMID- 29336791
TI - Robust inertia-free attitude takeover control of postcapture combined spacecraft
with guaranteed prescribed performance.
AB - In this paper, a robust inertia-free attitude takeover control scheme with
guaranteed prescribed performance is investigated for postcapture combined
spacecraft with consideration of unmeasurable states, unknown inertial property
and external disturbance torque. Firstly, to estimate the unavailable angular
velocity of combination accurately, a novel finite-time-convergent tracking
differentiator is developed with a quite computationally achievable structure
free from the unknown nonlinear dynamics of combined spacecraft. Then, a robust
inertia-free prescribed performance control scheme is proposed, wherein, the
transient and steady-state performance of combined spacecraft is first
quantitatively studied by stabilizing the filtered attitude tracking errors.
Compared with the existing works, the prominent advantage is that no parameter
identifications and no neural or fuzzy nonlinear approximations are needed, which
decreases the complexity of robust controller design dramatically. Moreover, the
prescribed performance of combined spacecraft is guaranteed a priori without
resorting to repeated regulations of the controller parameters. Finally, four
illustrative examples are employed to validate the effectiveness of the proposed
control scheme and tracking differentiator.
PMID- 29336792
TI - An Ounce of Prevention May Be Worth Many Pounds of Cure.
PMID- 29336794
TI - Tubercular Dactylitis in a Young Boy.
PMID- 29336795
TI - The Breathing Effort of Very Preterm Infants at Birth.
AB - OBJECTIVE: To compare the respiratory effort of very preterm infants receiving
positive pressure ventilation (PPV) with infants breathing on continuous positive
airway pressure (CPAP), directly after birth. STUDY DESIGN: Recorded
resuscitations of very preterm infants receiving PPV or CPAP after birth were
analyzed retrospectively. The respiratory effort (minute volume and recruitment
breaths [>8 mL/kg], heart rate, oxygen saturation, and oxygen requirement were
analyzed for the first 2 minutes and in the fifth minute after birth. RESULTS:
Respiratory effort was analyzed in 118 infants, 87 infants receiving PPV and 31
infants receiving CPAP (median gestational age, 28 weeks [IQR, 26-29] vs 29 weeks
[IQR, 29-30; P < .001); birth weight, 1059 g [IQR, 795-1300] vs 1205 g [IQR, 956
1418; P = .06]). The minute volume of spontaneous breaths of infants receiving
PPV was lower at 2 minutes (37 mL/kg/minute [IQR, 15-69] vs 188 mL/kg/minute
[IQR, 128-297; P < .001]) and at 5 minutes (112 mL/kg/minute [IQR, 46-229] vs 205
mL/kg/minute [IQR, 174-327; P < .001]). Recruitment breaths occurred less in the
PPV group at 2 minutes (0 breaths/minute [IQR, 0-1] vs 4 breaths/minute [IQR, 1
8; P < .001]) and 5 minutes (0 breaths/minute [IQR, 0-3] vs 2 breaths/minute
[IQR, 0-11; P = .01). The heart rate was lower in the PPV group (94 beats/minute
[IQR, 68-128] vs 124 beats/minute [IQR, 100-144; P = .02]) as was oxygen
saturation (50% [IQR, 35%-66%] vs 67% [IQR, 34%-80%; P = .04]), but not different
at 5 minutes (heart rate, 149 beats/minute [IQR, 131-162] vs 150 beats/minute
[IQR, 132-160; P = NS]; oxygen saturation , 91% [IQR, 80%-95%] vs 92% [IQR, 89%
97%; P = NS]). The oxygen requirement was higher (at 2 minutes, 30% [IQR, 21%
53%] vs 21% [IQR, 21%-29%; P = .05]; at 5 minutes, 39% [IQR, 22%-91%] vs 22%
[IQR, 21%-31%; P = .003]). CONCLUSION: Very preterm infants breathe at birth when
receiving PPV, but the respiratory effort was significantly lower when compared
with infants receiving CPAP only. The reduced breathing effort observed likely
justified applying PPV in most infants.
PMID- 29336796
TI - An Unusual Cause of Abdominal Pain.
PMID- 29336797
TI - Deficit of Fat Free Mass in Very Preterm Infants at Discharge is Associated with
Neurological Impairment at Age 2 Years.
AB - Preterm infants have a deficit of fat-free mass accretion during hospitalization.
This study suggests that z score of fat-free mass at discharge is associated with
neurologic outcome (P = .003) at 2 years of age, independent of sex, gestational
age, and birth weight z score. Interventions to promote quality of growth should
be considered.
PMID- 29336793
TI - Hand Preference and Cognitive, Motor, and Behavioral Functioning in 10-Year-Old
Extremely Preterm Children.
AB - The association of hand preference (left, mixed, and right) with cognitive,
academic, motor, and behavioral function was evaluated in 864 extremely preterm
children at 10 years of age. Left-handed and right-handed children performed
similarly but mixed-handed children had greater odds of functional deficits
across domains than right-handed children.
PMID- 29336798
TI - Hospital Readmissions in Children with Pulmonary Hypertension: A Multi
Institutional Analysis.
AB - OBJECTIVE: To assess the rate of and risk factors for 30-day hospital readmission
in children with pulmonary hypertension. STUDY DESIGN: The Pediatric Health
Information System database was analyzed for patients <=18 years old with
pulmonary hypertension (International Classification of Diseases, Ninth Revision,
diagnosis codes of 416.0, 416.1, 416.8, or 416.9) admitted from 2005 through
2014. A generalized hierarchical regression model was used to determine
significant ORs and 95% CIs associated with 30-day readmission. RESULTS: A total
of 13580 patients met inclusion criteria (median age 1.7 years [IQR 0.3-8.7],
45.3% with congenital heart disease). Admissions increased 4-fold throughout the
study period. Associated hospital charges increased from $119 million in 2004 to
$929 million in 2014. During initial admission, 57.4% of patients required
admission to the intensive care unit, and 48.2% required mechanical ventilation.
The 30-day readmission rate was 26.3%. Mortality during readmission was 4.2%.
Factors increasing odds of readmission included a lower hospital volume of
pulmonary hypertension admissions (1.41 [1.23-1.57], P < .001) and having public
insurance (1.26 [1.16-1.38], P < .001). Decreased odds of readmission were
associated with older age and the presence of congenital heart disease (0.86
[0.79-0.93], P < .001). CONCLUSIONS: The pediatric pulmonary hypertension
population carries significant morbidity, as reflected by a high use of intensive
care unit resources and a high 30-day readmission rate. Younger patients and
those with public insurance represent particularly at-risk groups.
PMID- 29336800
TI - Oral Granular Cell Tumor Mimicking a Giant Sialolith in a Child.
PMID- 29336799
TI - Access to High Pediatric-Readiness Emergency Care in the United States.
AB - OBJECTIVE: To determine the geographic accessibility of emergency departments
(EDs) with high pediatric readiness by assessing the percentage of US children
living within a 30-minute drive time of an ED with high pediatric readiness, as
defined by collaboratively developed published guidelines. STUDY DESIGN: In this
cross-sectional analysis, we examined geographic access to an ED with high
pediatric readiness among US children. Pediatric readiness was assessed using the
weighted pediatric readiness score (WPRS) of US hospitals based on the 2013
National Pediatric Readiness Project (NPRP) survey. A WPRS of 100 indicates that
the ED meets the essential guidelines for pediatric readiness. Using estimated
drive time from ZIP code centroids, we determined the proportions of US children
living within a 30-minute drive time of an ED with a WPRS of 100 (maximum), 94.3
(90th percentile), and 83.6 (75th percentile). RESULTS: Although 93.7% of
children could travel to any ED within 30 minutes, only 33.7% of children could
travel to an ED with a WPRS of 100, 55.3% could travel to an ED with a WPRS at or
above the 90th percentile, and 70.2% could travel to an ED with a WPRS at or
above the 75th percentile. Among children within a 30-minute drive of an ED with
the maximum WPRS, 90.9% lived closer to at least 1 alternative ED with a WPRS
below the maximum. Access varied across census divisions, ranging from 14.9% of
children in the East South Center to 56.2% in the Mid-Atlantic for EDs scoring a
maximum WPRS. CONCLUSION: A significant proportion of US children do not have
timely access to EDs with high pediatric readiness.
PMID- 29336801
TI - Fixing nature's mistakes on the aortic valve: Will the normal form ensure normal
function in the long term?
PMID- 29336802
TI - Resection of pleural implants in patients with lung cancer should remain the
exception rather than the rule.
PMID- 29336803
TI - Postoperative cognitive dysfunction related to Alzheimer disease?
PMID- 29336804
TI - Primum non nocere-it takes a village.
PMID- 29336805
TI - Height supersedes weight: Height-diameter indexing keeps you ahead of the game.
PMID- 29336806
TI - Variety is the spice of life: One-stage or two-stage repair of extensive chronic
thoracic aortic dissection.
PMID- 29336807
TI - Functionalized metal-organic framework nanocomposites for dispersive solid phase
extraction and enantioselective capture of chiral drug intermediates.
AB - The facile preparation, characterization and application of a novel magnetic
graphene oxide- metal organic framework [Zn2(d-Cam)2(4, 4'-bpy)]n (MGO-ZnCB) as a
sorbent for fast, simple and enantioselective capture of chiral drug
intermediates are presented in this paper. The MGO-ZnCB nanocomposite, developed
by encapsulating MGO nanoparticles into the homochiral metal organic framework of
ZnCB, can integrate the advantages from each component endowing the hybrids with
improved synergystic effects. The enantioselective performance of MGO-ZnCB was
evaluated by dispersive magnetic nanoparticle solid phase extraction (d-MNSPE) of
1, 1'-bi-2-naphthol (BN) and 2, 2'-furoin (Furoin) racemic solutions. Due to the
excellent dispersive capability, high stability, relatively larger saturation
magnetization and distinct enrichment capacity of MGO-ZnCB, the d-MNSPE method
provids good enantioselective separation of these compounds with enantiomeric
excess (ee) values as high as 74.8% and 57.4%, respectively. The entire process
with BN or Furoin can be completed within 3 min or less. After washing with
methanol, the host MGO-ZnCB can be easily recycled and reused six times without
any apparent loss of performance. Furthermore, the adsorbed BN and Furoin in
nanodomains of the MGO-ZnCB composite were directly investigated for the first
time by atomic force microscopy-infrared (AFM-IR) technique.
PMID- 29336808
TI - Miniaturized solid-phase extraction of macrolide antibiotics in honey and bovine
milk using mesoporous MCM-41 silica as sorbent.
AB - A simple and effective method of miniaturized solid-phase extraction (mini-SPE)
was developed for the simultaneous purification and enrichment of macrolide
antibiotics (MACs) (i.e. azithromycin, clarithromycin, erythromycin, lincomycin
and roxithromycin) from honey and skim milk. Mesoporous MCM-41 silica was
synthesized and used as sorbent in mini-SPE. Several key parameters affecting the
performance of mini-SPE procedure were thoroughly investigated, including sorbent
materials, amount of sorbent and elution solvents. Under the optimized condition,
satisfactory linearity (r2 > 0.99), acceptable precision (RSDs, 0.3-7.1%), high
sensitivity (limit of detection in the range of 0.01-0.76 MUg/kg), and good
recoveries (83.21-105.34%) were obtained. With distinct advantages of simplicity,
reliability and minimal sample requirement, the proposed mini-SPE procedure
coupled with ultrahigh performance liquid chromatography and quadrupole time-of
flight tandem mass spectrometry could become an alternative tool to analyze the
residues of MACs in complex food matrixes.
PMID- 29336809
TI - Screening of break point cluster region Abelson tyrosine kinase inhibitors by
capillary electrophoresis.
AB - In the present study, a capillary electrophoresis (CE) method was developed for
screening of inhibitors against the break point cluster region Abelson tyrosine
kinase (BCR-ABL). The screening method was established by using 5
carboxyfluorescein labeled peptide substrate of BCR-ABL (F-ABLS), a known BCR-ABL
tyrosine kinase inhibitor dasatinib, as well as a small chemical library
consisting of 37 natural products. Thus, the inhibition of BCL-ABL kinase by
small inhibitors was assayed by a CE system equipped with the laser induced
fluorescence detector. The yield of phosphorylated product could be precisely
measured through the separation by CE. The method is competent for enzymatic
inhibition assay as well as the measurement of the inhibition kinetics. For
screening BCR-ABL tyrosine kinase inhibitors, the hits were readily identified
once the peak area of the phosphorylated products was reduced in comparison with
the negative control. By taking the advantage of the screening method, luteolin
and epicatechin gallate were discovered as the new BCR-ABL inhibitors.
PMID- 29336811
TI - Discussion.
PMID- 29336810
TI - Does adjuvant radiation provide any survival benefit after an R1 resections for
pancreatic cancer?
AB - BACKGROUND: The benefit of adding external beam radiation to adjuvant
chemotherapy in patients that have undergone a margin positive resection for
early stage, pancreatic ductal adenocarcinoma has not been determined
definitively. METHODS: The National Cancer Data Base was queried to evaluate the
utility of adjuvant radiation in patients with pathologic stage I-II pancreatic
ductal adenocarcinoma who underwent upfront pancreatoduodenectomy with a positive
margin (margin positive resection) between 2004 and 2013. RESULTS: In the study,
1,392 patients met inclusion criteria, of whom 263 (18.9%) were lymph node
negative (pathologic stages IA, IB, IIA) and 1,129 (81.1%) were node-positive
(pathologic stage IIB); 938 (67.4%) patients received adjuvant radiation and
chemotherapy, while 454 (32.6%) received adjuvant chemotherapy alone. Cox
modeling stratified by nodal status demonstrated the benefit of radiation to be
statistically significant only in node positive patients (hazard ratio 0.81, 95%
confidence interval, 0.71-0.93). Node-positive patients receiving adjuvant
radiation and chemotherapy had an adjusted median survival of 17.5 months vs 15.2
months for those receiving adjuvant chemotherapy alone (P=.003). In patients who
had negative nodes, there was no difference in overall survival with radiation
(22.5 vs 23.6 months, P=.511). CONCLUSION: Addition of radiation to adjuvant
chemotherapy after a margin positive resection confers a survival benefit albeit
limited (about 2 months) in patients with node-positive pancreatic head cancer.
(Surgery 2017;160:XXX-XXX.).
PMID- 29336812
TI - Enhancing surgical performance by adopting expert musicians' practice and
performance strategies.
AB - BACKGROUND: Surgery is a performing art-each surgical procedure is a live
performance that has immediate and irreversible consequences for both the
performer and the audience. Surgeons operate with surgical instruments, whereas
musicians perform with musical instruments. Both perform in high-stress, high
risk work environments, where small errors in motor performance or judgment can
have immediate negative consequences. While there is abundant literature on
musical performance and their impact on outcome, little similar research has been
published in the field of surgery. We aimed at identifying expert musicians'
practice and performance strategies that may aid surgeons to enhance their
surgical performance. METHODS: In the study, 82 relevant English-language
articles from 1974 to 2017 matched applicable search terms. Nominal Group
Technique was applied to identify 5 key domains that comprise important parallels
between surgical and expert musical performance. RESULTS: The 5 key domains
identified were: (1) extensive training and deliberate practice, (2) dexterity
and ambidexterity, (3) performance evaluation and competition, (4) performance
related injuries, and (5) performance anxiety. We found focused and mindful
training in motor performance, not performing immediately after a hiatus from
practice, training to improve the precision and responsiveness of the nondominant
hand, continuous and critical self-evaluation, training in injury recognition and
prevention, and pharmacologic factors to be of utmost importance. CONCLUSION:
Critical parallels exist between surgical and expert musical performance that may
improve surgical outcomes by adopting musicians' strategies for combating
physiological and psychologic performance-related issues. Raising surgeons'
awareness for this subject content may improve surgical performance and patient
outcomes, as well as help prevent occupational injuries.
PMID- 29336813
TI - Recurrence after curative-intent resection of perihilar cholangiocarcinoma:
analysis of a large cohort with a close postoperative follow-up approach.
AB - BACKGROUND: Although several studies have been conducted on the patterns of
recurrence in resected perihilar cholangiocarcinoma, they have many limitations.
The aim of this study was to investigate recurrence after resection and to
evaluate prognostic factors on the time to recurrence and recurrence-free
survival. METHODS: Consecutive patients who underwent curative-intent resection
of perihilar cholangiocarcinoma between 2001 and 2012 were reviewed
retrospectively. The Cox proportional hazards model was used for multivariable
analysis. RESULTS: In the study period, 402 patients underwent resection of
perihilar cholangiocarcinoma (R0, n = 340; R1, n = 62). Radial margin positivity
(n = 43, 69%) was the most common reason for R1 resection. The median follow-up
of survivors was 7.4 years. The cumulative recurrence probability was higher in
R1 than in R0 resection (86% vs 57% at 5 years, P < .001). Seventeen R0 patients
had a recurrence over 5 years after resection. There was no difference in median
survival time after recurrence between R0 and R1 resection (10 vs 7 months). The
proportion of isolated locoregional recurrence was higher in R1 than in R0
resection (37% vs 16%, P < .001), whereas the proportion of distant recurrence
was similar. In R0 resection, the independent prognostic factors for time to
recurrence and recurrence-free survival were microscopic venous invasion and
lymph node metastasis. CONCLUSION: More than half of patients with perihilar
cholangiocarcinoma experience recurrence after R0 resection. These recurrences
occur frequently within 5 years but occasionally after 5 years, which emphasizes
the need for close and long-term surveillance. Adjuvant strategies should be
considered, especially for patients with nodal metastasis or venous invasion even
after R0 resection.
PMID- 29336814
TI - Inhibition of Interleukin-10 in the tumor microenvironment can restore mesothelin
chimeric antigen receptor T cell activity in pancreatic cancer in vitro.
AB - BACKGROUND: Pancreatic cancer cells are known to shield themselves from
immunosurveillance by secreting immune inhibitory cytokines such as Interleukin
10. Using mesothelin, a differentiating antigen that is overexpressed in
pancreatic cancer, we assessed the negative effect of the tumor microenvironment
on chimeric antigen receptor T cell-based immunotherapy and its reversal via
depletion of Interleukin-10. METHODS: T cells cultured in pancreatic cancer-cell
conditioned medium were transduced with lentiviruses encoding mesothelin-chimeric
antigen receptor in the presence or absence of anti-Interleukin-10-blocking
antibody. RESULTS: Coculture supernatants of conditioned medium displayed
significant inhibition of interferon gamma and granzyme B secretion, both of
which are crucial for induction of target cell cytotoxicity. In contrast, this
inhibition was restored toward baseline when conditioned medium was Interleukin
10- depleted (p < .05 for both interferon gamma and granzyme B). In addition, we
observed a significant decrease in mesothelin-chimeric antigen receptor T cell
induced cytotoxicity of BxPC-3 target cells in the presence of conditioned
medium. Furthermore, we observed a partial blunting of this inhibition when
Interleukin-10 was depleted from the conditioned medium. CONCLUSION: Substantial
reversal of tumor-derived immunosuppression may be achieved by blocking
Interleukin-10 in the local microenvironment, allowing for more effective
cytotoxicity of mesothelin-engrafted chimeric antigen receptor T cells and
enhancing the potential for clinical application.
PMID- 29336815
TI - Impact of restricted intraoperative fluid infusion on liver dysfunction after
portal venous embolization protocols for major hepatectomy.
PMID- 29336816
TI - Traumatic thoracic rib cage hernias: Operative management and proposal for a new
anatomic-based grading system.
AB - BACKGROUND: Traumatic Rib Cage Hernias (TRCH) requiring operative repair are rare
and there is currently no literature to guiding surgical management. METHODS:
Perioperative review of TRCH over 32 years. Five operative grades were developed
based on extent of tissue/bone damage, size, and location. RESULTS: Twenty-four
patients (20 blunt, 4 penetrating) underwent operative repair. Lung was the
herniated organ in 88% with a median of 4 rib fractures and average size of 60.25
cm. Types of operation were well clustered by assigned TRCH grade. The majority
required mesh (75%) and/or rib plating (79%). Complex tissue flap reconstruction
was required in 10%. Full range-of-motion was maintained in 88% with79% returning
to pre-injury activity levels. Five patients had continued pain at final follow
up (mean = 7months). CONCLUSION: The size and degree of injury has important
implications in the optimal surgical management of TRCHs. These operative grades
effectively direct surgical care for these rare and complex injuries.
PMID- 29336817
TI - Neurocognitive assessment in patients with a minor traumatic brain injury and an
abnormal initial CT scan: Can cognitive evaluation assist in identifying patients
who require surveillance CT brain imaging?
AB - BACKGROUND: Evidence for repeat computed tomography (CT) in minor traumatic brain
injury (mTBI) patients with intracranial pathology is scarce. The aim of this
study was to investigate the utility of clinical cognitive assessment (COG) in
defining the need for repeat imaging. METHODS: COG performance was compared with
findings on subsequent CT, and need for neurosurgery in mTBI patients (GCS 13-15
and positive CT findings). RESULTS: Of 152 patients, 65.8% received a COG (53.0%
passed). Patients with passed COG underwent fewer repeat CT (43.4% vs. 78.7%; p =
.001) and had shorter LOS (8.7 vs. 19.5; p < .05). Only 1 patient required
neurosurgery after a passed COG. The negative predictive value of a normal COG
was 90.6% (95%CI = 81.8%-95.4%). CONCLUSION: mTBI patients with an abnormal index
CT who pass COG are less likely to undergo repeat CT head, and rarely require
neurosurgery. The COG warrants further investigation to determine its role in
omitting repeat head CT.
PMID- 29336818
TI - Discussion of "Breast cancer in women under 50: Most are not high risk".
PMID- 29336819
TI - Identification of a Corticohabenular Circuit Regulating Socially Directed
Behavior.
AB - BACKGROUND: The prefrontal cortex (PFC) has been implicated in the
pathophysiology of social dysfunction, but the specific circuit partners
mediating PFC function in health and disease are unclear. METHODS: The excitatory
designer receptor exclusively activated by designer drugs (DREADD) hM3Dq was used
to induce PFC activation during social behavior measured in the three-chamber
sociability assay (rats/mice). Functional magnetic resonance imaging was combined
with hM3Dq-mediated PFC activation to identify novel nodes in the "social brain"
in a hypothesis-free manner. In multiplexed DREADD experiments, hM3Dq and the
inhibitory KORDi were used to bidirectionally modulate PFC activity and measure
social behavior and global functional magnetic resonance imaging signature. To
characterize the functional role of specific nodes identified in this functional
magnetic resonance imaging screen, we used anterograde and retrograde tracers,
optogenetic and DREADD-assisted circuit mapping, and circuit behavioral
experiments. RESULTS: PFC activation suppressed social behavior and modulated
activity in a number of regions involved in emotional behavior. Bidirectional
modulation of PFC activity further refined this subset of brain regions and
identified the habenula as a node robustly correlated with PFC activity.
Furthermore, we showed that the lateral habenula (LHb) receives direct synaptic
input from the PFC and that activation of LHb neurons or the PFC inputs to the
LHb suppresses social preference. Finally, we demonstrated that LHb inhibition
can prevent the social deficits induced by PFC activation. CONCLUSIONS: The LHb
is thought to provide reward-related contextual information to the mesolimbic
reward system known to be involved in social behavior. Thus, PFC projections to
the LHb may represent an important part of descending PFC pathways that control
social behavior.
PMID- 29336820
TI - Micro-CT and micro-FE analysis of pedicle screw fixation under different loading
conditions.
AB - Anchorage of pedicle screw instrumentation in the elderly spine with poor bone
quality remains challenging. In this study, micro finite element (uFE) models
were used to assess the specific influence of screw design and the relative
contribution of local bone density to fixation mechanics. These were created from
micro computer tomography (uCT) scans of vertebras implanted with two types of
pedicle screws, including a full region-or-interest of 10 mm radius around each
screw, as well as submodels for the pedicle and inner trabecular bone of the
vertebral body. The local bone volume fraction (BV/TV) calculated from the uCT
scans around different regions of the screw (pedicle, inner trabecular region of
the vertebral body) were then related to the predicted stiffness in simulated
pull-out tests as well as to the experimental pull-out and torsional fixation
properties mechanically measured on the corresponding specimens. Results show
that predicted stiffness correlated excellently with experimental pull-out
strength (R2 > 0.92, p < .043), better than regional BV/TV alone (R2 = 0.79, p =
.003). They also show that correlations between fixation properties and BV/TV
were increased when accounting only for the pedicle zone (R2 = 0.66-0.94, p <=
.032), but with weaker correlations for torsional loads (R2 < 0.10). Our analyses
highlight the role of local density in the pedicle zone on the fixation stiffness
and strength of pedicle screws when pull-out loads are involved, but that local
apparent bone density alone may not be sufficient to explain resistance in
torsion.
PMID- 29336821
TI - Validation of radiostereometric analysis in six degrees of freedom for use with
reverse total shoulder arthroplasty.
AB - A phantom study was conducted to determine bias in motion and bias at zero motion
of radiostereometric analysis (RSA) for evaluating implant relative displacement
in reverse total shoulder arthroplasty (RTSA). A Sawbones shoulder phantom was
fitted with a RTSA implant set and 13 tantalum markers. The model was fixed to a
manual micrometer, providing controlled movements though fifteen known increments
in translation and twelve increments in rotation (0.02-5.00 mm and 0.1-6.0
degrees ), along each translation and rotation axis. Movement between the glenoid
and humerus was assessed using beads vs. beads (B/B), model vs. beads (M/B), and
model vs. model (M/M) measurement methods in a model-based RSA environment. Bias
in motion and bias at zero motion were defined as the difference between measured
and accepted reference values, and the difference between double examinations
with a theoretical displacement of zero, respectively. Bias in motion ranged from
0.054 +/- 0.010 to 0.129 +/- 0.014 mm and 0.076 +/- 0.025 to 0.126 +/- 0.025
degrees (B/B), 0.023 +/- 0.009 to 0.126 +/- 0.016 mm and 0.111 +/- 0.033 to
0.794 +/- 0.251 degrees (M/B), and 0.029 +/- 0.010 to 0.135 +/- 0.030 mm and
0.243 +/- 0.088 to 0.384 +/- 0.153 degrees (M/M). Bias at zero motion ranged
from 0.120 to 0.156 mm and 0.075 to 0.206 degrees (B/B), 0.074 to 0.149 mm and
0.067 to 1.953 degrees (M/B), and 0.069 to 0.259 mm and 0.284 to 1.273 degrees
(M/M). This is the first RSA for RTSA study, with results comparable to those
validating the use of RSA for hip and knee arthroplasties (accepted as 0.05-0.50
mm and 0.15-1.15 degrees ), justifying the potential use of RSA as a tool for
measuring implant displacement in the shoulder.
PMID- 29336822
TI - Role of Color Doppler Ultrasound in the Diagnosis of Idiopathic Facial Aseptic
Granuloma.
PMID- 29336823
TI - A reliable and easy to transport quality control method for chlamydia and
gonorrhoea molecular point of care testing.
AB - Quality control (QC) is an essential component of point-of-care testing programs.
In the context of a randomised-controlled trial (TTANGO) using GeneXpert (Xpert)
Chlamydia trachomatis and Neisseria gonorrhoeae (CT/NG) point-of-care testing in
remote areas of Australia, we aimed to develop and utilise a stable positive
control material. Bacterial cultures of CT and NG were resuspended together to
provide cycle threshold (Ct) values of approximately 25 cycles for both CT and NG
when tested on the Xpert CT/NG assay. These positive control suspensions were
dried in aliquots, heat inactivated, and then provided to 12 participating health
services as research-only QC samples in kit form. At each service, a QC sample
was resuspended and tested each month on the Xpert. QC results, including Xpert
Ct values, were analysed from each site over 30 months and we calculated costs
per QC sample. Overall, at 12 health services there were 89 QC samples tested
(average of 8 tests per site per year). Mean Ct values for the 89 controls
samples were 25.25 cycles (SD = 1.15) for CT, 24.04 cycles (SD = 1.400) for one
NG target and 23.35 cycles (SD = 1.55) for the other NG target. No significant
differences in Ct value for CT or NG controls were observed over a trial period
of 30 months. Positive QC samples for research use in a trial of a molecular
point-of-care assay were inexpensive to produce and stable when stored at 2-8
degrees C. For routine use, additional requirements such as meeting National
Association of Testing Authority (NATA) regulations and Therapeutic Goods
Administration (TGA) approval will need to be achieved.
PMID- 29336824
TI - Trait-based characterization of species transported on Japanese tsunami marine
debris: Effect of prior invasion history on trait distribution.
AB - Nearly 300 coastal marine species collected from >630 debris items from the 2011
Great East Japan earthquake and tsunami have landed alive along the North
American Pacific coast and the Hawaiian Archipelago. We synthesized life history,
environmental, and distributional traits for 103 of these species and compared
species with (n=30) and without (n=62) known invasion histories. The species
represent 12 phyla, and Mollusca, Crustacea, and Bryozoa accounted for 71 of the
103 species. The majority are native to the Northwest Pacific and the Central
Indo-Pacific. Species with known invasion history were more common on artificial
and hardpan substrates, in temperate reef, fouling, and flotsam habitats, at
subtropical and tropical temperatures, and exhibited greater salinity tolerance
than species with no prior invasion history. Thirty-five Japanese tsunami marine
species without prior invasion history overlapped in ordination trait space with
known invaders, indicating a subset of species in this novel assemblage that
possess traits similar to species with known invasion history.
PMID- 29336825
TI - Detecting the occurrence of indigenous and non-indigenous megafauna through
fishermen knowledge: A complementary tool to coastal and port surveys.
AB - Marine bioinvasions and other rapid biodiversity changes require today
integrating existing monitoring tools with other complementary detection
strategies to provide a more efficient management. Here we explored the efficacy
of fishermen observations and traditional port surveys to effectively track the
occurrence of both indigenous and non-indigenous megafauna in the Adriatic Sea.
This consisted mainly of mobile taxa such as fishes, crustaceans and molluscs.
Port surveys using traps and nets within 10 major Adriatic harbours, were
compared with the information obtained from 153 interviews with local fishermen.
Information gathered by traps and nets varied significantly and generally
resulted of limited efficacy in exotic species detection. Interviews allowed
tracking the occurrence of new species through time and space, providing
complementary knowledge at the low cost. This combined approach improves our
capability of being informed on the arrival of species of different origin,
providing a more rational, improved basis for environmental management and
decision making.
PMID- 29336827
TI - Significant changes in CMS pharmacy services F-Tags for long-term care
facilities.
PMID- 29336828
TI - What is new in the world of immunizations for 2018.
PMID- 29336829
TI - What don't we know about bladder control and why does it matter? An AGS-NIA
collaborative conference sought answers - and progress.
PMID- 29336830
TI - Interdisciplinary development and implementation of a dementia skills training
program in a VA community living center: a pilot study.
AB - This pilot study investigates the usefulness of a dementia care training program
developed by an interdisciplinary team to address problem behaviors associated
with dementia. Staff members of a VA Community Living Center completed an 8-hour
workshop covering fundamental knowledge about dementia and instruction in skills
to use with patients through video, lecture, and role-plays. Measures on dementia
knowledge and perceived self-efficacy were completed by staff members before and
after the workshop. Results revealed increases in self-efficacy and knowledge,
with particular gains in general knowledge of dementia and communicating with
patients. Younger staff members scored higher on tests of knowledge at pre- and
post-test, whereas staff members with more years of work experience rated their
self-efficacy higher at post-test only. There was an associated decrease in
assaultive behaviors by patients with dementia in the year this workshop was
implemented. Results highlight the benefit of interdisciplinary collaboration in
developing educational content and the value of providing staff training on
managing dementia-related behaviors. Adjustments to this training program are
discussed.
PMID- 29336831
TI - Ultraviolet radiation significantly enhances the molecular response to dispersant
and sweet crude oil exposure in Nematostella vectensis.
AB - Estuarine organisms are subjected to combinations of anthropogenic and natural
stressors, which together can reduce an organisms' ability to respond to either
stress or can potentiate or synergize the cellular impacts for individual
stressors. Nematostella vectensis (starlet sea anemone) is a useful model for
investigating novel and evolutionarily conserved cellular and molecular responses
to environmental stress. Using RNA-seq, we assessed global changes in gene
expression in Nematostella in response to dispersant and/or sweet crude oil
exposure alone or combined with ultraviolet radiation (UV). A total of 110
transcripts were differentially expressed by dispersant and/or crude oil
exposure, primarily dominated by the down-regulation of 74 unique transcripts in
the dispersant treatment. In contrast, UV exposure alone or combined with
dispersant and/or oil resulted in the differential expression of 1133
transcripts, of which 436 were shared between all four treatment combinations.
Most significant was the differential expression of 531 transcripts unique to one
or more of the combined UV/chemical exposures. Main categories of genes affected
by one or more of the treatments included enzymes involved in xenobiotic
metabolism and transport, DNA repair enzymes, and general stress response genes
conserved among vertebrates and invertebrates. However, the most interesting
observation was the induction of several transcripts indicating de novo synthesis
of mycosporine-like amino acids and other novel cellular antioxidants. Together,
our data suggest that the toxicity of oil and/or dispersant and the complexity of
the molecular response are significantly enhanced by UV exposure, which may co
occur for shallow water species like Nematostella.
PMID- 29336832
TI - Anticoagulation in neonatal ECMO.
AB - Despite advances made in technology and neonatal intensive care, the rate of
hemorrhagic and thrombotic complications remains unacceptably high in patients
undergoing extracorporeal membrane oxygenation (ECMO) and these complications
negatively impact morbidity and mortality. Management of anticoagulation in
neonates who have a developing hemostatic system is vastly different from adults
and poses unique challenges. Variation in practice among ECMO centers regarding
anticoagulation monitoring and titration reflects the lack of high-quality
evidence. Novel anticoagulants may offer alternative options, though their impact
on outcomes is yet to be demonstrated. In this chapter, we review the hemostatic
alterations that occur during ECMO with a focus on current approaches and
limitations to anticoagulation titration in neonates on ECMO.
PMID- 29336833
TI - Education for ECMO providers: Using education science to bridge the gap between
clinical and educational expertise.
AB - A well-organized educational curriculum for the training of both novice and
experienced ECMO providers is critical for the continued function of an
institutional ECMO program. ELSO provides guidance for the education for ECMO
specialists, physicians and staff, which incorporates "traditional" instructor
centered educational methods, such as didactic lectures and technical skill
training. Novel research suggests utilization of strategies that align with
principles of adult learning to promote active learner involvement and reflection
on how the material can be applied to understand existing and new constructs may
be more effective. Some examples include the "flipped classroom," e-learning,
simulation, and interprofessional education. These methodologies have been shown
to improve active participation, which can be related to improvements in
understanding and long-term retention. A novel framework for ECMO training is
considered. Challenges in assessment and credentialing are also discussed.
PMID- 29336834
TI - An overview of medical ECMO for neonates.
AB - Extracorporeal membrane oxygenation (ECMO), a life-saving therapy for respiratory
and cardiac failure, was first used in neonates in the 1970s. The indications and
criteria for ECMO have changed over the years, but it continues to be an
important option for those who have failed other medical therapies. Since the
Extracorporeal Life Support Organization (ELSO) Registry was established in 1989,
more than 29,900 neonates have been placed on ECMO for respiratory failure, with
84% surviving their ECMO course, and 73% surviving to discharge or transfer. In
this chapter, we will review the basics of ECMO, patient characteristics and
criteria, patient management, ECMO complications, special uses of neonatal ECMO,
and patient outcomes.
PMID- 29336836
TI - Current status of tissue engineering applied to bladder reconstruction in humans.
AB - CONTEXT AND OBJECTIVE: Bladder reconstruction is performed to replace or expand
the bladder. The intestine is used in standard clinical practice for tissue in
this procedure. The complications of bladder reconstruction range from those of
intestinal resection to those resulting from the continuous contact of urine with
tissue not prepared for this contact. In this article, we describe and classify
the various biomaterials and cell cultures used in bladder tissue engineering and
reviews the studies performed with humans. ACQUISITION OF EVIDENCE: We conducted
a review of literature published in the PubMed database between 1950 and 2017,
following the principles of the PRISM declaration. SYNTHESIS OF THE EVIDENCE:
Numerous in vitro and animal model studies have been conducted, but only 18
experiments have been performed with humans, with a total of 169 patients. The
current evidence suggests that an acellular matrix, a synthetic polymer with
urothelial and autologous smooth muscle cells attached in vitro or stem cells
would be the most practical approach for experimental bladder reconstruction.
CONCLUSIONS: Bladder replacement or expansion without using intestinal tissue is
still a challenge, despite progress in the manufacture of biomaterials and the
development of cell therapy. Well-designed studies with large numbers of patients
and long follow-up times are needed to establish an effective clinical
translation and standardisation of the check-up functional tests.
PMID- 29336835
TI - Standard whole prostate gland radiotherapy with and without lesion boost in
prostate cancer: Toxicity in the FLAME randomized controlled trial.
AB - PURPOSE: To compare toxicity rates in patients with localized prostate cancer
treated with standard fractionated external beam radiotherapy (EBRT) with or
without an additional integrated boost to the macroscopically visible tumour.
MATERIAL AND METHODS: FLAME is a phase 3 multicentre RCT (NCT01168479) of
patients with pathologically confirmed localized intermediate or high-risk
prostate cancer. The standard treatment arm (n = 287) received a dose to the
entire prostate of 77 Gy in 35 fractions. The dose-escalated treatment arm (n =
284) received 77 Gy in 35 fractions to the entire prostate, with an integrated
boost up to 95 Gy to the multi-parametric MRI-defined (macroscopic) tumour within
the prostate. Treatment related toxicity was measured using the CTCAE version
3.0. Grade 2 or worse GU or GI events up to two years were compared between
groups by presenting proportions and by Generalized Estimating Equations (GEE)
analyses for repeated measures. RESULTS: Ninety percent of the 571 men randomly
assigned between September 2009 and January 2015 had high-risk disease (Ash
2000), of whom nearly 66% were prescribed hormonal therapy up to three years.
Median follow-up was 55 months at the time of this analysis. Toxicity prevalence
rates for both GI and GU increased until the end of treatment and regressed
thereafter, with no obvious differences across treatment groups. Late cumulative
GI toxicity rates were 11.1% and 10.2% for the standard and dose-escalated group,
respectively. These rates were 22.6% and 27.1% for GU toxicity. GEE analyses
showed that both GU toxicity and GI toxicity (>=grade 2) up to two years after
treatment were similar between arms (OR 1.02 95%CI 0.78-1.33p = 0.81 and (OR 1.19
95%CI 0.82-1.73p = 0.38), respectively. CONCLUSIONS: In intermediate- and high
risk prostate cancer patients, focal dose escalation integrated with standard
EBRT did not result in an increase in GU and GI toxicity when compared to the
standard treatment up to two years after treatment. This suggests that the
described focal dose escalation technique is safe and feasible.
PMID- 29336837
TI - Effectiveness of definitive radiotherapy for squamous cell carcinoma of the vulva
with gross inguinal lymphadenopathy.
AB - OBJECTIVE: To evaluate the effectiveness and long-term side effects of definitive
groin radiotherapy for vulvar cancer with grossly involved inguinal lymph nodes.
METHODS: The records of 407 women with vulvar squamous cell carcinoma treated
with radiotherapy at one institution during 1992-2014 were reviewed to identify
patients who had radiographic or histologic evidence of grossly involved inguinal
lymph nodes. Patients with lymphadenectomy before radiotherapy and patients
treated for recurrent disease were excluded. Actuarial incidences of vulvar,
inguinal, and distant recurrences, the relationship between vulvar recurrence and
inguinal recurrence, and overall survival were analyzed using the Kaplan-Meier
method. RESULTS: Thirty-three patients were identified. The median age at
diagnosis was 64 years. The median long-axis radiographic diameter of the largest
inguinal lymph node or lymph node mass was 2.5 cm (range, 1.4-8.7). Sixteen
patients (48%) also had evidence of pelvic lymph node metastasis. The median
radiation dose delivered to grossly involved nodes was 66.0 Gy (range, 60.0
70.0). The 3-year actuarial incidences of vulvar, groin, and distant recurrences
were 24.2%, 17.7%, and 30.3%, respectively. With a median follow-up time of 28
months (range, 2-196), four patients (12%) had groin recurrence, of whom three
also had vulvar recurrence. There were few major late adverse effects of regional
radiotherapy. The 3-year overall survival rate was 51%. CONCLUSIONS: High-dose
volume-directed radiotherapy achieves a high rate of local control with low risk
of serious long-term toxic effects in patients with vulvar squamous cell
carcinoma and grossly involved inguinal lymph nodes.
PMID- 29336838
TI - Pediatric Concussion Update: What ED Nurses Should Know After "Humpty Dumpty"
Falls.
PMID- 29336839
TI - Effect of thymectomy on refractory autoimmune status epilepticus.
AB - Refractory status epilepticus (RSE) is an increasingly recognized manifestation
of autoimmune encephalitis, which can occur either as a paraneoplastic or non
paraneoplastic disorder. The effect of tumor removal in paraneoplastic status
epilepticus has never been explored systematically, although early tumor
treatment is usually recommended. In this study, we report clinical, pathological
and EEG findings of a patient who developed RSE as one of multiple paraneoplastic
manifestations of thymoma and the effect of thymectomy on seizure outcome. To our
knowledge, this is the first report of successful treatment of RSE with tumor
removal in paraneoplastic encephalitis.
PMID- 29336841
TI - Economic impact of the new oral treatments for multiple sclerosis.
AB - INTRODUCTION: Multiple sclerosis (MS) is a chronic disease affecting the central
nervous system and is characterised by inflammation, demyelination, gliosis, and
axonal damage. The introduction of dimethyl fumarate and teriflunomide has led to
an increase in the number of alternative first-line therapies for MS. The
objective of this study was to evaluate the economic impact of the incorporation
of new oral therapies at the reference unit (CSUR) at Hospital Universitario
Puerta de Hierro Majadahonda. MATERIALS AND METHODS: We performed a retrospective
observational study including patients diagnosed with MS, who underwent treatment
with disease-modifying drugs in 2015 and were followed up for a minimum mean time
of one year. Data were collected from patients' electronic clinical histories and
the pharmacy service's programme for dispensing drugs to outpatients. RESULTS:
Evaluating the cost of changing 125 patients' treatment from other drugs to
dimethyl fumarate and teriflunomide, and comparing this with the cost that would
have resulted from maintaining their previous treatment, demonstrated a total
saving of ?169,107.31 over the study period. CONCLUSIONS: In addition to
contributing new therapeutic alternatives, dimethyl fumarate and teriflunomide
produced an economic saving in MS treatment at our hospital.
PMID- 29336840
TI - Heterozygous TYROBP deletion (PLOSLFIN) is not a strong risk factor for cognitive
impairment.
AB - Biallelic loss-of-function mutations in TYROBP and TREM2 cause a rare disease
that resembles early-onset frontotemporal dementia with bone lesions called
polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy
(PLOSL). Some PLOSL-causing variants in TREM2 have also been associated with
Alzheimer's disease when heterozygous. Here, we studied the PLOSLFINTYROBP
deletion that covers 4 of the gene's 5 exons. We genotyped 3220 older Finns (mean
age 79, range 58-104) and found 11 deletion carriers (mean age 78, range 60-94).
The carrier prevalence was 0.0034 (1 in 293) that matches previous findings in
younger cohorts suggesting no significant early mortality. By comparing Mini
Mental State Examination (MMSE) scores and diagnoses of dementia, we did not find
any significant differences between TYROBP deletion carriers and noncarriers (all
p-values >0.5). Neuropathological analysis of 2 deletion carriers (aged 89 and 94
years) demonstrated only minimal beta amyloid pathology (Consortium to Establish
a Registry for Alzheimer's Disease (CERAD) score 0). Collectively these results
suggest that heterozygous carriership of the TYROBP deletion is not a major risk
factor of cognitive impairment.
PMID- 29336842
TI - Immunohistochemical localization of angiotensin AT1 receptors in the rat carotid
body.
AB - The carotid body (CB) is a major peripheral arterial chemoreceptor that initiates
respiratory and cardiovascular adjustments to maintain homeostasis. Recent
evidence suggests that circulating or locally produced hormones like angiotensin
II acting via AT1 receptors modulate its activity in a paracrine-autocrine
manner. The aim of this study was to examine the immunohistochemical localization
of AT1 receptor in the CB of adult rats and to compare its expression in vehicle
treated animals, and after the long-term application of its selective blocker
losartan. Immunohistochemistry revealed that a subset of CB glomeruli and the
vast majority of neurons in the adjacent superior cervical ganglion (SCG) were
strongly AT1 receptor-immunoreactive. In the CB immunostaining was observed in
the chemosensory glomus cells typically aggregated in cell clusters while the
nerve fibers in-between and large capillaries around them were immunonegative.
Exogenous administration of losartan for a prolonged time significantly reduces
the intensity of AT1 receptor immunostaining in the CB glomus cells and SCG
neurons. Our results show that AT1 receptors are largely expressed in the rat CB
under physiological conditions, and their expression is down-regulated by
losartan treatment.
PMID- 29336843
TI - Neuroprotective effects of quercetin 4'-O-beta-d-diglucoside on human striatal
precursor cells in nutrient deprivation condition.
AB - Several investigations have demonstrated neuroprotective effects of quercetin, a
polyphenol widely present in nature, against neurotoxic chemicals, as well as in
neuronal injury/neurodegenerative disease models. Most of these studies have been
performed with quercetin aglycone and its metabolites, while scanty data are
available on its glycosides. This study is aimed at investigating the
neuroprotective effects of quercetin 3,4'-O-beta-d-diglucoside (Q3,4'dG),
isolated from the bulbs of the white cultivar (Allium cepa L.), using an in vitro
model of human striatal precursor cells (HSPs), a primary culture isolated from
the striatal primordium and previously characterized. To study the effect of
Q3,4'dG on cell survival, HSPs were exposed to nutrient deprivation created by
replacing culture medium with phosphate buffer saline (PBS). Our findings showed
that Q3,4'dG treatment significantly promoted cell survival and strongly
decreased apoptosis induced by nutrient deprivation, as evaluated by cell
proliferation/death analyses. In addition, since the adhesive capacities of cells
are essential for cell survival, the expression of some adhesion molecules, such
as pancadherin and focal adhesion kinase, was evaluated. Interestingly, PBS
exposure significantly decreased the expression of both molecules, while in the
presence of Q3,4'dG this effect was prevented. This study provides evidence of a
neuroprotective role exerted by Q3,4'dG and suggests its possible implication in
sustaining neuronal survival for prevention and treatment of neurodegenerative
disorders.
PMID- 29336844
TI - Detecting and Avoiding Problems When Using the Cre-lox System.
AB - The Cre-lox recombination approach is commonly used to generate cell-specific
gene inactivation (or activation). We have noticed that the breeding and
genotyping sections of papers utilizing Cre-lox techniques are frequently
incomplete. While seemingly straightforward, there are important considerations
that need to be implemented in the breeding and genotyping methods to prevent the
introduction of experimental confounds. Germline recombination and transient
expression of Cre recombinase during development are some examples of the
complications that can occur, and conventional genotyping methods may fail to
identify these events. In this opinion article, we highlight the importance of
testing for unexpected recombination events, suggest strategies to isolate and
minimize adverse recombination events, and encourage editors and reviewers to
expect more definitive statements regarding the validation of genotyping.
PMID- 29336845
TI - Defining B Cell Chromatin: Lessons from EBF1.
AB - Hematopoiesis is regulated by signals from the microenvironment, transcription
factor networks, and changes of the epigenetic landscape. Transcription factors
interact with and shape chromatin to allow for lineage- and cell type-specific
changes in gene expression. During B lymphopoiesis, epigenetic regulation is
observed in multilineage progenitors in which a specific chromatin context is
established, at the onset of the B cell differentiation when early B cell factor
1 (EBF1) induces lineage-specific changes in chromatin, during V(D)J
recombination and after antigen-driven activation of B cells and terminal
differentiation. In this review, we discuss the epigenetic changes underlying B
cell differentiation, focusing on the role of transcription factor EBF1 in B cell
lineage priming.
PMID- 29336846
TI - Sex Differences in Prevalence of Emergency Department Patient Substance Use.
AB - PURPOSE: Substance use and misuse is prevalent in emergency department (ED)
populations. While the prevalence of substance use and misuse is reported, sex
specific trends in ED populations have not been documented. We set out to
determine the sex-specific prevalence of ED patient substance use during this
current epidemic. METHODS: A retrospective electronic data abstraction tool,
developed for quality-improvement purposes, was used to assess ED visits in 3
hospitals in northeastern Pennsylvania. All patients with ED diagnosis codes for
substance use F10.000 through F 19.999 (excluding F17 codes for nicotine) were
abstracted for network ED visits at all 3 hospitals. Data points included ED
clinical enrollment site, primary substance used, sex, date of ED visit,
disposition (including left without being seen, left against medical advice,
discharged, admitted, and treatment in rehabilitation) for 18 months (January 1,
2016 through July 31, 2017). The categorical parameters of sex, clinical
enrollment site, diagnosis, date of ED visit, and disposition status were
summarized as a proportion of the subject group. Time series analysis was used to
assess trends in substance use and misuse visits by patient sex. FINDINGS: A
total of 10,511 patients presented to the EDs during the study time period with a
final diagnosis of a substance use-related reason and were included in the
analysis. The mean age for these patients was 43.6 (SD 16.4) years, and the
majority was male (65.6%, n = 6900). The most common substance in the final
diagnosis for the ED visit was alcohol (54.3%; 95% CI, 53.3-55.2), followed by
opioids (19.2%; 95% CI, 18.4-19.9) and cannabis (14.4%; 95% CI, 13.7-15.0).
Females tended to be younger than males (42.4 years vs 44.3 years; P < 0.001),
and were more likely to be discharged after the ED visit than males (36.1% vs
32.3%; P < 0.001). When exploring differences in age by sex and substance, males
with a final diagnosis including alcohol- and cannabis-related issues were older
than females, whereas females diagnosed with opioid-related reasons were older
than males (41.3 vs 38.9 years; P < 0.001). IMPLICATIONS: There are sex-specific
differences in prevalence of patients presenting with substance use in the ED
setting.
PMID- 29336847
TI - Frequent contamination of nursing scrubs is associated with specific care
activities.
AB - BACKGROUND: The objective of this article is to assess health care worker (HCW)
and patient care factors associated with bacterial contamination of scrubs.
METHODS: We performed a cohort study of critical care HCWs. Participants were
given 4 sets of new scrubs; each set was sampled 8 times during the 8-month study
period on random days in the last 4 hours of the shift. Total colony counts and
presence of prespecified pathogenic bacteria were assessed. Generalized
estimating equation was used to identify factors associated with contamination.
RESULTS: There were 720 samples obtained from 90 HCWs; 30% of samples were
contaminated with pathogenic bacteria. Multivariate analysis showed that
providing care for patients with wounds (odds ratio [OR], 1.75; 95% confidence
interval [CI], 1.17-2.62; P < .01) or giving a bath (OR, 1.46; 95% CI, 0.96-2.22;
P = .07) was associated with higher odds of scrub contamination. A second model
showed the average log colony count of bacterial contamination of scrubs was
higher when a bath was given (log colony count difference, 0.21; P = .05) but
lower among HCWs assigned to care for at least 1 patient on contact precautions
(log colony count difference, 0.28; P < .01). CONCLUSIONS: HCW attire was
frequently contaminated with bacteria. Providing care for patients with wounds or
giving a bath were associated with scrub contamination by pathogenic bacteria.
However, the amount of contamination was lower among HCWs who were assigned to
care for patients on contact precautions.
PMID- 29336848
TI - Response to a letter to the Editor regarding the prospective evaluation of risk
factors and clinical influence of carbapenem resistance in children with gram
negative bacteria infection.
PMID- 29336849
TI - "Let's not hurry, but let's not waste time": The importance of appropriate
management of non-ST-elevation myocardial infarction.
PMID- 29336850
TI - Microvenous Reflux in the Skin of Limbs with Superficial Venous Incompetence.
AB - This study investigated whether microvenous reflux can be detected in limbs with
chronic venous disease using superb microvascular imaging (SMI) and colour
Doppler imaging. Participants with venous disease (limbs, n = 26) and without
venous disease (limbs, n = 10) were studied. The skin in the medial gaiter region
was imaged using both SMI and colour Doppler to identify reflux in the small
vessels in response to distal augmentation. The diameters and depths of
responsive vessels were measured. In limbs with venous disease, reflux in
response to provocation was visualised with SMI in a greater number of vessels
(12/26 versus 4/26) and smaller vessels than with colour Doppler. Reflux in the
superficial skin veins was demonstrated in one control participant (1/10) using
SMI and in none using colour Doppler (0/10). Our study indicates that microvenous
reflux is demonstrable in limbs with venous disease and that SMI is more
sensitive than colour Doppler.
PMID- 29336851
TI - Clinical Utility of Fetal Short-Lag Spatial Coherence Imaging.
AB - In this study, we evaluate the clinical utility of fetal short-lag spatial
coherence (SLSC) imaging. Previous work has documented significant improvements
in image quality with fetal SLSC imaging as quantified by measurements of
contrast and contrast-to-noise ratio (CNR). The objective of this study was to
examine whether this improved technical efficacy is indicative of the clinical
utility of SLSC imaging. Eighteen healthy volunteers in their first and second
trimesters of pregnancy were scanned using a modified Siemens SC2000 clinical
scanner. Raw channel data were acquired for routinely examined fetal organs and
used to generate fully matched raw and post-processed harmonic B-mode and SLSC
image sequences, which were subsequently optimized for dynamic range and other
imaging parameters by a blinded sonographer. Optimized videos were reviewed in
matched B-mode and SLSC pairs by three blinded clinicians who scored each video
based on overall quality, target conspicuity and border definition. SLSC imaging
was highly favored over conventional imaging with SLSC scoring equal to (28.2 +/-
10.5%) or higher than (63.9 +/- 12.9%) B-mode for video pairs across all examined
structures and processing conditions. Multivariate modeling revealed that SLSC
imaging is a significant predictor of improved image quality with p <= 0.002.
Expert-user scores for image quality support the application of SLSC in fetal
ultrasound imaging.
PMID- 29336852
TI - Brazilian species of Calliandra Benth. (tribe Ingeae) are nodulated by diverse
strains of Paraburkholderia.
AB - The Chapada Diamantina in NE of Brazil is a biodiversity hotspot and a center of
radiation for many Neotropical legume genera, such as Calliandra and Mimosa. The
present study aimed to evaluate nodulation in Calliandra species endemic to
various environments, and to characterize the diversity of their symbiotic
rhizobia using housekeeping (16S rRNA, recA) and plasmid-borne, symbiosis-related
(nifH and nodC) genes. The nodulation ability of selected isolates was assessed.
All of the 126 bacterial isolates from 18 Calliandra species collected in six
different vegetation types were identified as Paraburkholderia according to their
housekeeping and symbiosis gene phylogenies. They were grouped in seven clades in
relation to the dominant vegetation type in their native environments. The
majority, particularly those from highland "campo rupestre" vegetation, were
similar to Paraburkholderia nodosa, but had nodC genes identical to the Mimosa
symbiont Paraburkholderia tuberum sv. mimosae. The other smaller groups were
related to Paraburkholderia diazotrophica and Paraburkholderia sabiae, and some
single strains were not close to any known species. The symbionts of Calliandra
spp. in NE Brazil are Paraburkholderia strains closely-related to Mimosa
symbionts from the same region. NE Brazil is a reservoir of symbiotic
Paraburkholderia that have an affinity for genera in the Mimosoid clade.
PMID- 29336853
TI - Updated Guidelines on Infection Prevention in Pediatric Ambulatory Settings.
AB - The American Academy of Pediatrics (AAP) recently released updated guidelines on
infection control and prevention in pediatric outpatient settings. Key
recommendations include mandatory influenza vaccination for all healthcare
workers offered free to all staff, expanded guidance on infection control
practices for children with cystic fibrosis, guidance on additional prevention
procedures during community outbreaks of infectious diseases and recommendations
on improving communication between healthcare facilities when referring
potentially contagious patients. The new guidelines modify standard precautions
by indicating that gloves are not required for diaper changes or some body fluid
contact (nasal secretions and tears) in a well child, or when administering
vaccines. In addition, efforts should be made to minimize exposure to infections
from contaminated toys that cannot be cleaned including plush toys, cleaning toys
in waiting rooms each day and encouraging families to bring their own toys or
books to visits.
PMID- 29336854
TI - Morphologically-directed Raman spectroscopy for forensic soil analysis.
AB - Morphologically-directed Raman spectroscopy (MDRS) is a novel yet reliable
analytical technique that can be used for a variety of forensic applications,
enabling scientists to gain more information from samples than they obtain using
more traditional methods. In soil forensics, MDRS delivers particle size
distribution and microscopic morphological characteristics for the particles
present, and at the same time allows secure mineral identification. In this
article, we explore the benefits of utilizing soil in forensic investigations,
and demonstrate the value of applying MDRS. Two case studies illustrate the real
life potential and applications of this technology.
PMID- 29336855
TI - Update on Anemia in ESRD and Earlier Stages of CKD: Core Curriculum 2018.
AB - Anemia is a frequent complication during the later stages of chronic kidney
disease. When present, it may cause symptoms such as fatigue and shortness of
breath. The pathogenesis of anemia in chronic kidney disease is complex, but a
central feature is a relative deficit of erythropoietin. New information has
elucidated the critical role of the hypoxia-sensing system in mediating
erythropoietin synthesis and release. Iron deficiency is a second important
factor in the anemia of chronic kidney disease. New insights into the dynamics of
iron metabolism have clarified the role of chronic inflammation and hepcidin as
key mediators of impaired iron utilization. In this article, we review the
epidemiology, pathobiology, clinical evaluation, and treatment of anemia in
chronic kidney disease.
PMID- 29336856
TI - Evaluation of Kidney Donors: Core Curriculum 2018.
AB - Nearly 100,000 patients are waiting for a kidney transplant, yet each year only
11,000 undergo transplantation with a deceased donor kidney. Annual death rates
among waitlist registrants range from 5% to 15%; many die before receiving a
transplant. Not surprisingly, registrants turn to family and friends to become
living kidney donors on their behalf. Living kidney donor selection practices aim
to quantify lifetime risk for kidney failure based on a candidate's predonation
demographic and health characteristics. It has been established that estimated
lifetime risk for kidney failure varies considerably based on predonation
comorbid conditions, and as such, it is of paramount importance that potential
living donor candidates undergo proper medical, surgical, and psychosocial
screening before donation. This installment of AJKD's Core Curriculum in
Nephrology provides readers with the tools necessary for proper evaluation of
living kidney donor candidates.
PMID- 29336857
TI - Identifying Risk Factors for the Development of Stiffness After Revision Total
Knee Arthroplasty.
AB - BACKGROUND: Although there are several studies concerning manipulation under
anesthesia (MUA) after primary total knee arthroplasty, there is a paucity of
literature evaluating MUA after revision total knee arthroplasty (rTKA). The
purpose of this study was to determine the incidence, timing, and risk factors
associated with MUA after rTKA. METHODS: The Humana database was reviewed from
2007 to 2015 for all patients who underwent rTKA. Patients who underwent rTKA
followed by ipsilateral MUA were identified. Time to MUA was calculated monthly.
Possible risk factors analyzed included preoperative narcotic use, smoking,
anxiety and/or depression, diabetes, obesity, age, and sex. Multivariate logistic
regression was used to determine odds ratio. RESULTS: In total, 5414 rTKAs were
included in the study and 1.7% (n = 96) underwent MUA after surgery. Sixty-nine
percent of MUAs occurred within the first 3 months after rTKA. Young patients
(<50 years) had significantly higher odds of MUA after rTKA (6.5, P < .0001). No
difference in odds of MUA (1.0, P = .85) occurred between males and females. A
diagnosis of obesity, diabetes, anxiety and/or depression, previous history of
narcotic use, or a history of smoking demonstrated no increased risk of MUA after
rTKA. Multivariate logistic regression analysis demonstrated that younger age
remained predictive of higher odds of MUA after rTKA. CONCLUSION: In this large
multicenter cohort study, 1.7% of patients underwent MUA after rTKA and younger
patients were 6 times more likely to have a MUA than patients over 50 years old.
These data should serve to help counsel patients regarding their risk of MUA
after rTKA.
PMID- 29336858
TI - Are Ceramic Bearings Becoming Cost-Effective for All Patients?
AB - BACKGROUND: The purpose of this study is to analyze whether the cost for ceramic
on-polyethylene (C-PE) and ceramic-on-ceramic (COC) bearings used in primary
total hip arthroplasty (THA) was changing over time, and if the cost differential
between ceramic bearings and metal-on-polyethylene (M-PE) bearings was
approaching the previously published tipping point for cost-effectiveness of
$325. METHODS: A total of 245,077 elderly Medicare patients (65+) who underwent
primary THA between 2010 and 2015 were identified from the United States Medicare
100% national administrative hospital claims database. The inpatient hospital
cost, calculated using cost-to-charge ratios, and hospital payment were analyzed.
The differential cost of C-PE and COC bearings, compared to M-PE, were evaluated
using parametric and nonparametric models. RESULTS: After adjustment for patient
and clinical factors, and the year of surgery, the mean hospital cost and
payments for primary THA with a C-PE or COC was within +/-1% of the cost for
primary THA with M-PE bearings (P < .001). From the nonparametric analysis, the
median hospital cost was $318-$360 more for C-PE and COC than M-PE. The
differential in median Medicare payment for THA with ceramic bearings compared to
M-PE was <$100. Cost differentials were found to decrease significantly over time
(P < .001). CONCLUSION: Patient and clinical factors had a far greater impact on
the cost of inpatient THA surgery than bearing selection. Because we found that
costs and cost differentials for ceramic bearings were decreasing over time, and
approaching the tipping point, it is likely that the cost-effectiveness
thresholds relative to M-PE are likewise changing over time and should be
revisited in light of this study.
PMID- 29336859
TI - Effectiveness of chemotherapy counselling on self-esteem and psychological
affects among cancer patients in Malaysia: Randomized controlled trial.
AB - OBJECTIVES: The aim of this study was to implement and evaluate the outcomes of
chemotherapy counselling based on the "Managing Patients on Chemotherapy" module
on self-esteem and psychological affect (anxiety, depression) of cancer patients
by pharmacists in ten selected government hospitals in Peninsular Malaysia.
METHODS: A randomized control trial was conducted among 2120 cancer patients from
April 2016 to January 2017 in ten selected government hospitals in Peninsular
Malaysia. Cancer patients were randomly assigned to intervention and control
groups. The intervention group received chemotherapy counselling by pharmacists
based on the "Managing Patients on Chemotherapy" module. The outcomes were
assessed at baseline, 1st, 2nd and 3rd follow-ups after counselling. In the
course of data analysis; independent sample t-test, chi-square and two-way
repeated measures ANOVA were conducted. RESULTS: Mean scores of self-esteem in
the intervention group had significant difference in comparison with those of the
control group in the 1st, 2nd and 3rd follow-ups after counselling (P < 0.0001).
Also, among those with depression and anxiety at baseline, there was reduction in
depression and anxiety scores after the 1st, 2nd and 3rd follow-ups after
counselling (p < 0.05). CONCLUSION: Repetitive counselling by pharmacists based
on the "Managing Patients on Chemotherapy" module had positive effect on
improving self-esteem and psychological affect of cancer patients undergoing
chemotherapy in Peninsular Malaysia. PRACTICE IMPLICATIONS: This module can be
used for all Malaysian cancer patients undergoing chemotherapy to improving self
esteem and psychological affect.
PMID- 29336860
TI - Coaching to support men in making informed choices about prostate cancer
screening: A qualitative study.
AB - OBJECTIVE: The objective of this study was to examine the perceptions of men,
practice nurses (PNs) and general practitioners (GPs) on patient decision
coaching for prostate cancer screening. METHODS: Seven focus groups were
conducted with 47 participants, representing three stakeholder groups - men, GPs
and PNs. All focus group discussions were conducted by the same facilitator and
guided by a semi-structured interview schedule. Transcriptions were analysed by
thematic analysis. RESULTS: Knowledge about the merits of prostate cancer
screening was high amongst GPs, but limited with PNs and men. All groups saw the
value in PN-led decision coaching for men considering screening for prostate
cancer, but had reservations about its implementation in practice. Barriers to
implementing a decision coaching system with PNs included staffing and cost of
implementation. CONCLUSION: GPs, PNs and men identified benefits for the use of a
PN-led decision coaching support intervention to assist men with making an
informed choice about screening for prostate cancer. Stakeholders had
reservations about how a PN-led intervention would effectively work in clinical
practice. PRACTICE IMPLICATIONS: A feasibility study is required to examine
barriers and enablers to implementing a PN-led decision coaching process for
prostate cancer screening in the Australian primary healthcare setting.
PMID- 29336861
TI - Care guide use for repeated non-emergent complaints and its effect on emergency
department visit frequency.
PMID- 29336862
TI - Reconciling Supply and Demand for State and Local Public Health Staff in an Era
of Retiring Baby Boomers.
AB - INTRODUCTION: The purpose of this study is to reconcile public health workforce
supply and demand data to understand whether the expected influx of public health
graduates can meet turnover events. METHODS: Four large public health workforce
data sources were analyzed to establish measures of workforce demand, voluntary
separations, and workforce employees likely to retire at state and local health
departments. Data were collected in 2014-2016 and analyzed in 2016 and 2017.
Potential workforce supply (i.e., candidates with formal public health training)
was assessed by analyzing data on public health graduates. Supply and demand data
were reconciled to identify potential gaps in the public health workforce.
RESULTS: At the state and local level, ?197,000 staff are employed in health
departments. This is down more than 50,000 from 2008. In total, >=65,000 staff
will leave their organizations during fiscal years 2016-2020, with <=100,000
staff leaving if all planned retirements occur by 2020. During 2000-2015, more
than 223,000 people received a formal public health degree at some level. More
than 25,000 students will receive a public health degree at some level in each
year through 2020. CONCLUSIONS: Demands for public health staff could possibly be
met by the influx of graduates from schools and programs of public health.
However, substantial implications exist for transferal of institutional knowledge
and ability to recruit and retain the best staff to sufficiently meet demand.
PMID- 29336863
TI - Age-associated expression of vitamin D receptor and vitamin D-metabolizing
enzymes in the male reproductive tract and sperm of Hu sheep.
AB - The cellular response to 1,25-dihydroxyvitamin D3 (Vit D3; biologically active
form of Vitamin D) is complex and depends not only on Vitamin D receptor (VDR)
expression but also on cellular uptake of circulating Vit D3 and the presence and
activity of Vitamin D-metabolizing enzyme. This study evaluated the expression of
VDR and Vitamin D-metabolizing enzymes in the ram reproductive tract at different
developmental stages and in spermatozoa. Nearly all cell types in the testes and
epithelial cells of the caput, corpus, and cauda expressed VDR, CYP27B1, and
CYP24A1 proteins. The mRNA and protein expression of CYP2R1, CYP27A1, and CYP27B1
in the testes and cauda increased significantly with increasing age (P < 0.05).
However, epididymal VDR mRNA and protein expression showed no significant
difference (P < 0.05) between adult (9- and 24-month-old) and prepubertal (3
month-old) rams. Furthermore, VDR and CYP24A1 were mainly concentrated in the mid
piece of ejaculated or cauda epididymis spermatozoa or both. Additionally, VDR
and CYP27B1 mRNA and protein expression levels were significantly higher in
ejaculated spermatozoa than in cauda epididymal spermatozoa (P < 0.05). Moreover,
VDR and CYP24A1 expression was significantly higher in high-motility than in low
motility spermatozoa (P < 0.05). The diverse expression patterns of VDR and
Vitamin D-metabolizing enzymes in the ram reproductive tract at different
developmental stages and spermatozoa suggest it plays a potential role in
spermatogenesis.
PMID- 29336864
TI - Biochemical characterization, stability, and pathogen safety of a new fibrinogen
concentrate (fibryga(r)).
AB - Fibryga(r) is a new lyophilized fibrinogen concentrate for intravenous use for
the treatment of congenital fibrinogen deficiency. fibryga(r) is produced from
pooled human plasma and the final product is characterized by high purity,
integrity, and pathogen safety. Functional activity of fibrinogen was
demonstrated by cross-linking studies and thromboelastometry; integrity of the
fibrinogen molecule was demonstrated by size exclusion chromatography and the
detection of only trace amounts of activation markers in the final product.
Pathogen safety of fibryga(r) was proved by downscaling studies for the two
dedicated pathogen inactivation/removal steps, i.e. solvent detergent treatment
and nanofiltration. Fibryga(r) is stable for at least three years when stored at
room temperature. In conclusion, the performed studies demonstrated that
fibryga(r) meets the requirements for a state-of-the-art fibrinogen concentrate,
such as a satisfactory activity profile combined with a favorable pathogen safety
profile and stability.
PMID- 29336865
TI - Continuous Hyperfractionated Accelerated Radiotherapy (CHART) for Non-small Cell
Lung Cancer (NSCLC): 7 Years' Experience From Nine UK Centres.
AB - AIM: Continuous hyperfractionated accelerated radiotherapy (CHART) remains an
option to treat non-small cell lung cancer (NSCLC; NICE, 2011). We have
previously published treatment outcomes from 1998-2003 across five UK centres.
Here we update the UK CHART experience, reporting outcomes and toxicities for
patients treated between 2003 and 2009. MATERIALS AND METHODS: UK CHART centres
were invited to participate in a retrospective data analysis of NSCLC patients
treated with CHART from 2003 to 2009. Nine (of 14) centres were able to submit
their data into a standard database. The Kaplan-Meier method estimated survival
and the Log-rank test analysed the significance. RESULTS: In total, 849 patients
had CHART treatment, with a median age of 71 years (range 31-91), 534 (63%) were
men, 55% had undergone positron emission tomography-computed tomography (PET-CT)
and 26% had prior chemotherapy; 839 (99%) patients received all the prescribed
treatment. The median overall survival was 22 months with 2 and 3 year survival
of 47% and 32%, respectively. Statistically significant differences in survival
were noted for stage IA versus IB (33.2 months versus 25 months; P = 0.032) and
IIIA versus IIIB (20 months versus 16 months; P = 0.018). Response at 3 months
and outcomes were significantly linked; complete response showing survival of 34
months against 19 months, 15 months and 8 months for partial response, stable and
progressive disease, respectively (P < 0.001). Age, gender, performance status,
prior chemotherapy and PET-CT did not affect the survival outcomes. Treatment was
well tolerated with <5% reporting >=grade 3 toxicity. CONCLUSION: In routine
practice, CHART results for NSCLC remain encouraging and we have been able to
show an improvement in survival compared with the original trial cohort. We have
confirmed that CHART remains deliverable with low toxicity rates and we are
taking a dose-escalated CHART regimen forward in a randomised phase II study of
sequential chemoradiotherapy against other accelerated dose-escalated schedules.
PMID- 29336866
TI - Regulatory mechanisms of collagen expression by interleukin-22 signaling in
scleroderma fibroblasts.
AB - BACKGROUND: Various cytokines have been indicated to be involved in the
pathogenesis of systemic sclerosis (SSc). IL-22 is one of the member of IL-10
cytokine family, and several studies have implicated IL-22 signaling in the
pathogenesis of autoimmune diseases. OBJECTIVES: To clarify the role of IL-22 in
the regulatory mechanism of ECM expression and to determine the contribution of
IL-22 to the phenotype of SSc. METHODS: The effect of IL-22 on ECM expression in
normal fibroblasts was determined by using PCR array, real-time PCR and
immunoblotting. microRNA expression was evaluated by real-time PCR. The
expression levels of IL-22 in the skin and sera were determined by using
immunohistochemical staining and ELISA. RESULTS: IL-22 significantly increased
the expression of type I collagen protein without changing its mRNA levels in
cultured normal human dermal fibroblast. The expression of let-7a, one of the
microRNAs which have negative effect on type I collagen expression, was
significantly decreased by the treatment with IL-22 in dermal fibroblasts. There
was no significant difference in the serum levels of IL-22 between SSc patients
and control subjects. However, the expression of IL-22 was detected in the
infiltrated lymphocytes in the SSc dermis, but not in normal dermis. IL-22
receptors were expressed in both normal and SSc dermal fibroblasts to the similar
extent. CONCLUSION: IL-22 expressed in infiltrated lymphocytes may stimulate the
up-regulation of type I collagen protein in dermal fibroblasts via let-7a down
regulation in SSc skin.
PMID- 29336867
TI - Nevus-like lesions on the lip and the foot.
PMID- 29336868
TI - The therapeutic potential of targeting the peripheral endocannabinoid/CB1
receptor system.
AB - Endocannabinoids (eCBs) are internal lipid mediators recognized by the
cannabinoid-1 and -2 receptors (CB1R and CB2R, respectively), which also mediate
the different physiological effects of marijuana. The endocannabinoid system,
consisting of eCBs, their receptors, and the enzymes involved in their
biosynthesis and degradation, is present in a vast number of peripheral organs.
In this review we describe the role of the eCB/CB1R system in modulating the
metabolism in several peripheral organs. We assess how eCBs, via activating the
CB1R, contribute to obesity and regulate food intake. In addition, we describe
their roles in modulating liver and kidney functions, as well as bone remodeling
and mass. Special importance is given to emphasizing the efficacy of the recently
developed peripherally restricted CB1R antagonists, which were pre-clinically
tested in the management of energy homeostasis, and in ameliorating both obesity-
and diabetes-induced metabolic complications.
PMID- 29336870
TI - Trends in Singing Voice Research: An Innovative Approach.
AB - OBJECTIVES: The objectives of this study were to trace and describe research
patterns in singing voice, to compare the amount of published research over time,
to identify journals that published most papers on "singing voice," and to
establish the most frequent research topics. MATERIALS AND METHODS: The study
uses qualitative and quantitative approaches through descriptive statistics, text
mining, and clustering. The authors conducted a search to identify scientific
papers. The titles and abstracts were analyzed regarding word frequency and
relations between them, through hierarchical cluster analysis and co-occurrence
networks. The frequency of journals was calculated, as well as the amount of
papers across time. RESULTS: Since 1949, 754 papers were published and an
increase was noticed. Even though 162 journals were identified by the authors,
the Journal of Voice holds the majority of papers, in every analyzed period. An
evolution of studied topics is described. Up to 2010, the main theme was
professional singers, especially classical and opera interpreters. Since then,
voice quality and the effects of training gathered more attention. CONCLUSIONS:
The growing interest in singing has been conspicuous since the first indexed
paper. However, it has been slightly slowing down. Until 2010, great importance
was given to the voice quality of singers and their occupational demands.
Acoustic analysis was widely used to study the effects of training. Since 2010,
the concern with functionality is increasing, rather than the organic voice
structures. Musical perception studies have been a trend, as well as the use of
electroglottography.
PMID- 29336869
TI - Long-term Average Spectra Analysis of Voice in Children With Cleft Palate.
AB - OBJECTIVES: The purpose of this study was to survey the spectral characteristics
and to compare, using an acoustic analyzer, the objective data obtained from
patients with cleft palates with the objective data of normal children using long
term average spectra (LTAS) analysis. METHODS: Participants were divided into a
clinical group and a control group. All participants were asked to practice
reading a sentence to become fluent. The duration of each recording was about 60
seconds. All samples were subjected to acoustic analysis using Praat software.
All recordings were analyzed acoustically using LTAS. RESULTS: In this study,
there was no significant difference between the control group and the clinical
group in the low-frequency region (boys: 0-2720 Hz; girls: 0-2240 Hz). LTAS
measurements showed a great difference between the control group and the clinical
group in the middle-frequency region (boys: 2720-4000 Hz; girls: 2240-4000 Hz).
We also found that the energy distributed in the clinical group was lower than
that of the control group in the high-frequency region (4000 Hz-8000 Hz) in both
boys and girls. CONCLUSIONS: The results reveal a lack of flat region in the
middle-frequency range in the clinical group (both boys and girls) in comparison
with the control group. The results also reveal that there is no significant
difference across the control group and the clinical group in the low-frequency
region.
PMID- 29336871
TI - Epigenetic regulation of the kappa opioid receptor gene by an insertion-deletion
in the promoter region.
AB - Preclinical and clinical studies have demonstrated that the kappa opioid receptor
(KOR) regulates reward, hedonic tone and emotions. At therapeutic level, on-going
clinical trials are assessing the potential of targeting the KOR for the
management of depression, anxiety disorders and substance use disorders. However,
genetic polymorphisms in the KOR gene that potentially contribute to its
implication in these phenotypes have been poorly studied. Here we investigated an
insertion-deletion in the promoter region of KOR (rs35566036), recently
associated with alcohol addiction, in a cohort of depressed subjects who died by
suicide, as well as psychiatrically healthy individuals. Focusing on 3 brain
regions (anterior insula, anterior cingulate cortex, and mediodorsal thalamus),
we characterized the functional impact of this structural variant on the
expression and patterns of DNA methylation of the KOR gene, using qPCR and
targeted Bisulfite-Sequencing, respectively. While there was no significant
change in the expression of KOR as a function of the insertion-deletion, or as a
function of disease status in any brain region, we found that this variant
strongly determines DNA methylation in KOR promoter, leading to a significant
decrease in methylation levels of 8 nearby CpG dinucleotides located
approximately 500 base pairs upstream the transcription start site. In addition,
our results suggest a possible association between the insertion-deletion and
depression; however, this result should be tested in larger populations. In sum,
in this study we uncovered an epigenetic mechanism potentially contributing to
KOR dysfunction in carriers of the insertion-deletion.
PMID- 29336872
TI - Abundance of ribosomal RNA gene copies in the genomes of schizophrenia patients.
AB - OBJECTIVE: The ribosome is a critical component of the translation machinery. The
key component of ribosomes is ribosomal RNA (rRNA). Dysregulation of rRNA
biogenesis has been implicated in some human diseases. One of the factors
affecting rRNA biogenesis is the ribosomal RNA genes (rDNA) copy number in the
genome. The aim of this study was to examine the rDNA copy number (CN) variation
in the genomes of patients with schizophrenia (SZ) compared to healthy controls
(HC). METHODS: We evaluated rDNA CN in leukocytes of 179 subjects with SZ (108
male/71 female) in comparison with 122 HC (60 male/62 female) using two
techniques: qPCR and nonradioactive quantitative hybridization (NQH), which is
based on the use of biotinylated rDNA probes. RESULTS: rDNA CN (NQH) and rDNA CN
(qPCR) was higher in SZ patients than in controls (median 542 vs 384, p=10-25 and
median 498 vs 370, p=10-12). NQH was experimentally proved to be less sensitive
to severe DNA damage than qPCR. The more DNA damage, the higher the ratio R=CN
(NQH)/CN (qPCR). 15% of the SZ patients had significantly higher rDNA damage
degree than the HC. CONCLUSION: Genomes of some SZ patients contain more
ribosomal genes than those of HC. The elevated ribosomal genes copy number in
human genome can be one of the genetic factors of schizophrenia development. This
hypothesis requires further experimental studies to be corroborated or disproved.
PMID- 29336874
TI - Regioselectivity of thiouracil alkylation: Application to optimization of
Darapladib synthesis.
AB - Darapladib is one of the most potent Lp-PLA2 (Lipoprotein-associated
phospholipase A2) inhibitor with an IC50 of 0.25 nM. We demonstrate that a
crucial step of Darapladib synthesis was not correctly described in the
literature, leading to the production of wrong regioisomers. Moreover we show
that the inhibitory activity is directly linked to the position on N1 since
compounds bearing alkylation on different sites have potentially less interaction
within the active site of Lp-PLA2.
PMID- 29336873
TI - Optimization of novel monobactams with activity against carbapenem-resistant
Enterobacteriaceae - Identification of LYS228.
AB - Metallo-beta-lactamases (MBLs), such as New Delhi metallo-beta-lactamase (NDM-1)
have spread world-wide and present a serious threat. Expression of MBLs confers
resistance in Gram-negative bacteria to all classes of beta-lactam antibiotics,
with the exception of monobactams, which are intrinsically stable to MBLs.
However, existing first generation monobactam drugs like aztreonam have limited
clinical utility against MBL-expressing strains because they are impacted by
serine beta-lactamases (SBLs), which are often co-expressed in clinical isolates.
Here, we optimized novel monobactams for stability against SBLs, which led to the
identification of LYS228 (compound 31). LYS228 is potent in the presence of all
classes of beta-lactamases and shows potent activity against carbapenem-resistant
isolates of Enterobacteriaceae (CRE).
PMID- 29336875
TI - Systems pharmacology dissection of the anti-stroke mechanism for the Chinese
traditional medicine Xing-Nao-Jing.
AB - Xing-Nao-Jing (XNJ) is a well-known injection that has been extensively applied
in clinical treatment of stroke in China. However, the underlying mechanism of
clinical administration of XNJ in stroke remains unclear. In this study, a
systems pharmacology strategy based on pharmacokinetic and pharmacodynamics data
was applied to analyze the pharmacological effect of XNJ on stroke. Sixteen
active compounds were filtered from XNJ through Drug-likeness (DL) and Brain
blood-barrier (BBB) evaluations. Ninety-four potential targets of these active
components were identified by SysDT and SEA. Biological process and pathway
enrichment analyses of these targets demonstrated that XNJ exerted anti-stroke
effects by biological processes and pathways, such as the response to oxidative
stress, regulation of blood pressure, calcium signaling pathway, and apoptosis.
Integrating the compound-target network and stroke-related PPI network, we found
that Akt1, HIF-1alpha and ITGB2 may play key roles in the treatment of stroke.
The experiments demonstrated that oxycurcumenol may prevent PC12 cells from
oxidative stress-induced cell damage. Our study indicates that XNJ has an effect
on stroke by protecting neuro cells from oxidative stress-induced cell damage via
HIF1alpha, and the research strategy at the systems pharmacology level is
feasible to reveal the mechanisms of novel lead compounds from natural products.
PMID- 29336876
TI - Structural Basis of Heterochromatin Formation by Human HP1.
AB - Heterochromatin plays important roles in transcriptional silencing and genome
maintenance by the formation of condensed chromatin structures, which determine
the epigenetic status of eukaryotic cells. The trimethylation of histone H3
lysine 9 (H3K9me3), a target of heterochromatin protein 1 (HP1), is a hallmark of
heterochromatin formation. However, the mechanism by which HP1 folds chromatin
containing H3K9me3 into a higher-order structure has not been elucidated. Here we
report the three-dimensional structure of the H3K9me3-containing dinucleosomes
complexed with human HP1alpha, HP1beta, and HP1gamma, determined by cryogenic
electron microscopy with a Volta phase plate. In the structures, two H3K9me3
nucleosomes are bridged by a symmetric HP1 dimer. Surprisingly, the linker DNA
between the nucleosomes does not directly interact with HP1, thus allowing
nucleosome remodeling by the ATP-utilizing chromatin assembly and remodeling
factor (ACF). The structure depicts the fundamental architecture of
heterochromatin.
PMID- 29336877
TI - Sin-quadratic model for chest tomosynthesis respiratory signal analysis and its
application in four dimensional chest tomosynthesis reconstruction.
AB - Chest tomosynthesis (CTS) is a newly developed imaging technique which provides
pseudo-3D volume anatomical information of thorax from limited-angle projections
and contains much less of superimposed anatomy than the chest X-ray radiography.
One of the relatively common problems in CTS is the patient respiratory motion
during image acquisition, which negatively impacts the detectability. In this
work, we propose a sin-quadratic model to analyze the respiratory motion during
CTS scan, which is a real time method where the respiratory signal is generated
by extracting the motion of diaphragm from projection radiographs. According to
the estimated respiratory signal, the CTS projections were then amplitude-based
sorted into four to eight phases, and an iterative reconstruction strategy with
total variation regularization was adopted to reconstruct the CTS images at each
phase. Simulated digital XCAT phantom data and three sets of patient data were
adopted for the experiments to validate the performance of the sin-quadratic
model and its application in four dimensional (4D) CTS reconstruction. Results of
the XCAT phantom simulation study show that the correlation coefficient between
the extracted respiratory signal and the originally designed respiratory signal
is 0.9964, which suggests that the proposed model could exactly extract the
respiratory signal from CTS projections. The 4D CTS reconstructions of both the
phantom data and the patient data show clear reduction of motion-induced blur.
PMID- 29336878
TI - Healing of Periapical Lesions after Endodontic Treatment with the GentleWave
Procedure: A Prospective Multicenter Clinical Study.
AB - INTRODUCTION: This report includes outcomes for a group of patients with
significant periapical lesions who were treated and evaluated in two single-arm,
multicenter, prospective, nonsignificant risk clinical studies. METHODS: Forty
five teeth were from 45 patients who met the inclusion criteria and consented for
the clinical studies and were diagnosed with periapical lesions with periapical
index score >=3. Patients were treated with a standardized treatment protocol
including instrumentation to an apical diameter of #20 without orifice
enlargement, the GentleWave Procedure, and warm vertical obturation. Clinical
signs and radiographic assessments were evaluated at 12 months to assess healing.
Success was classified as healing or healed and accounted for the cumulative
success rate of healing. Statistical analyses were performed by using Fisher
exact test, Pearson correlation, and multivariate logistic regression analyses.
RESULTS: At 12 months, 44 of 45 teeth (97.8%) were evaluated. The cumulative
success rate for the GentleWave Procedure was 97.7%. Forty-three of 44 teeth were
completely functional; all teeth had complete resolution for measured indices of
mobility, soft tissue lesions, sinus tract, and furcation involvement. No
patients experienced moderate or severe pain at 2, 7, and 14 days after
procedure. Although only 1 patient was unsuccessful and the presence of clinical
symptoms and type of periradicular diagnosis at 12 months were correlated with an
unsuccessful outcome, the analyses were limited by the sample size. CONCLUSIONS:
In this case series analysis, treatment of sizable periapical lesions with the
GentleWave Procedure resulted in a success rate of 97.7% at 12-month re
evaluation.
PMID- 29336879
TI - Effect of Dynamic Immersion in Sodium Hypochlorite and EDTA Solutions on Cyclic
Fatigue Resistance of WaveOne and WaveOne Gold Reciprocating Nickel-titanium
Files.
AB - INTRODUCTION: The purpose of this study was to evaluate the effect of sodium
hypochlorite (NaOCl) and EDTA solutions on the cyclic fatigue resistance of
WaveOne (WO) and WaveOne Gold (WOG) nickel-titanium reciprocating files. METHODS:
A hundred WO (25/.08), and 100 WOG (25/.07) were randomly divided into 5 groups:
group 1, no immersion; group 2, immersion in 5.25% NaOCl at 37 degrees C +/- 1
degrees C for 5 minutes; group 3, immersion in 5.25% NaOCl at 37 degrees C +/- 1
degrees C for 10 minutes; group 4, immersion in 17% EDTA at 37 degrees C +/- 1
degrees C for 5 minutes; and group 5, immersion in 17 % EDTA at 37 degrees C +/-
1 degrees C for 10 minutes. Then, the instruments were reciprocated in an
artificial canal until fracture occurred, and the time to fracture was recorded.
The data were statistically analyzed using 1-way analysis of variance and the
Student t test via SPSS 21.0 software (IBM Corp, Armonk, NY) with the
significance level set at P < .05. RESULTS: The cyclic fatigue resistance of the
WOG was statistically higher than the WO in all the conditions tested (P < .05).
There was no statistically significant difference among the different conditions
tested in terms of cyclic fatigue resistance for both WO and WOG files (P > .05).
Among the groups, there was no significant difference in the fracture lengths (P
> .05). CONCLUSIONS: Within the limitations of the present study, it was
determined that NaOCl and EDTA solutions did not have any effect on the cyclic
fatigue resistance of WO and WOG files.
PMID- 29336880
TI - Marginal Gaps between 2 Calcium Silicate and Glass Ionomer Cements and Apical
Root Dentin.
AB - INTRODUCTION: The outcome of periapical surgery has been directly improved with
the introduction of novel material formulations. The aim of the study was to
compare the retrograde obturation quality of the following materials: calcium
silicate (Biodentine; Septodont, Saint-Maur-des-Fosses, France), mineral trioxide
aggregate (MTA+; Cerkamed Company, Stalowa Wola, Poland), and glass ionomer
cement (Fuji IX; GC Corporation, Tokyo, Japan). METHODS: Materials' wettability
was calculated concerning the contact angles of the cements measured using a
glycerol drop. Cements' porosity was determined using mercury intrusion
porosimetry and micro-computed tomographic (MUCT) imaging. Extracted upper human
incisors were retrofilled, and MUCT analysis was applied to calculate the volume
of the gap between the retrograde filling material and root canal dentin.
Experiments were performed before and after soaking the materials in simulated
body fluid (SBF). RESULTS: No statistically significant differences were found
among the contact angles of the studied materials after being soaked in SBF. The
material with the lowest nanoporosity (Fuji IX: 2.99% and 4.17% before and after
SBF, respectively) showed the highest values of microporosity (4.2% and 3.1%
before and after SBF, respectively). Biodentine had the lowest value of
microporosity (1.2% and 0.8% before and after SBF, respectively) and the lowest
value of microgap to the root canal wall ([10 +/- 30] * 10-3 mm3). CONCLUSIONS:
Biodentine and MTA possess certain advantages over Fuji IX for hermetic
obturation of retrograde root canals. Biodentine shows a tendency toward the
lowest marginal gap at the cement-to-dentin interface.
PMID- 29336881
TI - Influence of Contracted Endodontic Access on Root Canal Geometry: An In Vitro
Study.
AB - INTRODUCTION: Contracted endodontic cavities (CECs) have developed from the
concept of minimally invasive dentistry and provide an alternative to traditional
endodontic cavities (TECs). They have been designed in an effort to preserve the
mechanical stability of teeth. The contracted cavity design preserves more of the
dentin but may influence the geometric shaping parameters. The aim of this micro
computed tomographic study was to evaluate the influence of contracted endodontic
cavities on the preservation of the original root canal anatomy after shaping
with nickel-titanium rotary instruments. METHODS: Thirty extracted human
mandibular molars with fully formed apices and independent mesial canals were
randomly assigned to group 1 (TEC) and group 2 (CEC). Each group was shaped using
ProGlider (Dentsply Maillefer, Ballaigues, Switzerland) and WaveOne Gold
(Dentsply Maillefer). Irrigation was performed with 10% EDTA and 5% sodium
hypochlorite. Samples were scanned before and after canal shaping to match canal
volumes (SkyScan; Bruker microCT, Kontich, Belgium [100 kV, 100 MUA, and 15-MUm
resolution]), and images were analyzed to evaluate canal volumes, surface areas,
and centroid shift on cross sections at -1 mm and -3 mm from the apex. RESULTS:
TECs showed a greater preservation of the original root canal anatomy with less
apical transportation than CECs, possibly because of the absence of coronal
interferences and, therefore, fewer pecking motions required to complete
instrumentation. CONCLUSIONS: Within the limitations of this study, TECs may lead
to a better preservation of the original canal anatomy during shaping compared
with CECs, particularly at the apical level.
PMID- 29336882
TI - Histobacteriologic Conditions of the Apical Root Canal System and Periapical
Tissues in Teeth Associated with Sinus Tracts.
AB - INTRODUCTION: This histobacteriologic study described the pattern of
intraradicular and extraradicular infections in teeth with sinus tracts and
chronic apical abscesses. METHODS: The material comprised biopsy specimens from
24 (8 untreated and 16 treated) roots of teeth associated with apical
periodontitis and a sinus tract. Specimens were obtained by periradicular surgery
or extraction and were processed for histobacteriologic and histopathologic
methods. RESULTS: Bacteria were found in the apical root canal system of all
specimens, in the main root canal (22 teeth) and within ramifications (17 teeth).
Four cases showed no extraradicular infection. Extraradicular bacteria occurred
as a biofilm attached to the outer root surface in 17 teeth (5 untreated and 12
treated teeth), as actinomycotic colonies in 2 lesions, and as planktonic cells
in 2 lesions. Extraradicular calculus formation (mineralized biofilm) was evident
in 10 teeth. CONCLUSIONS: Teeth with chronic apical abscesses and sinus tracts
showed a very complex infectious pattern in the apical root canal system and
periapical lesion, with a predominance of biofilms.
PMID- 29336883
TI - Long-term Prognosis of Pulpal Status of Traumatized Teeth Exhibiting
Contradictory Results between Pulp Sensibility Test and Ultrasound Doppler
Flowmetry: A Retrospective Study.
AB - INTRODUCTION: In this retrospective study, we investigated long-term (over 3
years) follow-up results of teeth that exhibited contradictory results between
the pulp sensibility test (thermal or electric pulp test) and ultrasound Doppler
flowmetry (UDF) until 1 year after trauma to inspect the prognosis of the pulp.
METHODS: Data were collected from the records of trauma patients in our hospital
between February 2012 and May 2015. The teeth that had continuously shown
contrasting results on the pulp sensibility test and UDF until 1 year after
trauma were chosen for the study. Cases with follow-up records of more than 3
years after trauma were finally included, and a retrospective chart review was
performed. RESULTS: Data from 343 teeth in 147 patients who visited the hospital
with traumatic dental injuries were examined. Among these, 13 teeth from 7
patients were included, and the record of each case was reviewed. All the
subjects showed negative responses on the pulp sensibility test and positive
responses on UDF until 1 year after trauma. Ultimately, 8 of the 13 teeth
recovered pulp sensibility. Two teeth failed to recover pulp sensibility and
became symptomatic; root canal treatment was performed on the teeth. The
remaining 3 teeth belonged to patients suffering from nerve damage; therefore,
the pulp sensibility test was not feasible. CONCLUSIONS: Based on this study, UDF
can be effectively used for the evaluation of pulpal status in traumatized teeth.
PMID- 29336884
TI - Effect of Torsional and Fatigue Preloading on HyFlex EDM Files.
AB - INTRODUCTION: The purpose of this study was to evaluate the effect of a low
amount of torsional preloading on the fatigue life and different degrees of
cyclic fatigue on torsional failure of HyFlex EDM (EDM; Coltene-Whaledent,
Allstetten, Switzerland) and HyFlex CM (CM; Coltene-Whaledent) instruments.
METHODS: EDM and CM files were used. The fatigue resistance was examined in a 5
mm radius and 60 degrees single curve, and the mean number of cycles to failure
(Nf) was recorded. The torque and rotation angles at failure of the instruments
were measured according to ISO 3630-1. New files were precycled to 0%, 50%, and
75% of the Nf, and torsional tests were then performed. Other new files were
preloaded at 5%, 15%, 25%, and 50% of the mean rotation angles before the fatigue
test. The fracture surfaces of the fragments were examined under a scanning
electron microscope. RESULTS: The fatigue resistance of EDM instruments was
higher than that of CM instruments (P < .05). The torque and angle of rotation at
fracture of the files were similar. Torsional preloading lowered the Nf of EDM at
15% preloading (P < .05) and the Nf of CM at 50% preloading (P < .05). However,
the Nf of EDM files even with 50% torsional preloading was significantly higher
than unused CM files (P < .05). Fatigue prestressing even at 75% had no negative
effect on the torque and rotation angle of the EDM files. Moderate precycling
(50%) of EDM files increased their torsional resistance. The fractographic
patterns corresponded to the pattern defined by the last stage test. CONCLUSIONS:
A low amount (15%) of torsional preloading reduced the fatigue resistance of EDM
files, whereas even extensive (75%) precyclic fatigue was not detrimental to
their torsional resistance.
PMID- 29336885
TI - Structural Basis for Activity and Specificity of an Anticoagulant Anti-FXIa
Monoclonal Antibody and a Reversal Agent.
AB - Coagulation factor XIa is a candidate target for anticoagulants that better
separate antithrombotic efficacy from bleeding risk. We report a co-crystal
structure of the FXIa protease domain with DEF, a human monoclonal antibody that
blocks FXIa function and prevents thrombosis in animal models without detectable
increased bleeding. The light chain of DEF occludes the FXIa S1 subsite and
active site, while the heavy chain provides electrostatic interactions with the
surface of FXIa. The structure accounts for the specificity of DEF for FXIa over
its zymogen and related proteases, its active-site-dependent binding, and its
ability to inhibit substrate cleavage. The inactive FXIa protease domain used to
obtain the DEF-FXIa crystal structure reversed anticoagulant activity of DEF in
plasma and in vivo and the activity of a small-molecule FXIa active-site
inhibitor in vitro. DEF and this reversal agent for FXIa active-site inhibitors
may help support clinical development of FXIa-targeting anticoagulants.
PMID- 29336886
TI - Can the Syndesmosis Procedure Prevent Metatarsus Primus Varus and Hallux Valgus
Deformity Recurrence? A 5-Year Prospective Study.
AB - One of the main objectives of hallux valgus surgery is correction of the
metatarsus primus varus deformity by osteotomy, arthrodesis, or soft tissue
correction. The syndesmosis procedure uses intermetatarsal cerclage sutures to
realign the first metatarsal and also induces a syndesmotic bonding between the
first and second metatarsals to prevent metatarsus primus varus deformity
recurrence. The purpose of the present study was to demonstrate radiologic
evidence of the effectiveness of the syndesmosis concept and to identify the
incidence and nature of deformity recurrence. A total of 55 feet from 60
consecutive procedures were followed regularly at 6 fixed points for 5 years. The
radiologic inclusion criterion was a first intermetatarsal angle >9 degrees or
metatarsophalangeal angle >20 degrees . The initial postoperative radiographs
showed significant correction of the intermetatarsal angle from a preoperative
average of 14.5 degrees to 4.3 degrees (p < .0001). It had increased to 7.0
degrees during the first 6 postoperative months but remained within the normal
upper limit of 9 degrees and exhibited no further significant changes for the
subsequent 4.5 years (p = .0792). Hallux valgus deformity correction also
correlated with metatarsus primus varus deformity correction. Three (5%) second
metatarsal stress fractures occurred, and all recovered uneventfully. In
conclusion, we have report the findings from a detailed medium long-term follow
up study showing, to the best of our knowledge, for the first time that
metatarsus primus varus and hallux valgus deformities can be effectively
corrected and maintained using a specific surgical technique. Also included are 6
relevant radiographs and photographs of the included and excluded feet in the
online Supplementary Material for reference.
PMID- 29336887
TI - GroEL Ring Separation and Exchange in the Chaperonin Reaction.
AB - The bacterial chaperonin GroEL and its cofactor, GroES, form a nano-cage for a
single molecule of substrate protein (SP) to fold in isolation. GroEL and GroES
undergo an ATP-regulated interaction cycle to close and open the folding cage.
GroEL consists of two heptameric rings stacked back to back. Here, we show that
GroEL undergoes transient ring separation, resulting in ring exchange between
complexes. Ring separation occurs upon ATP-binding to the trans ring of the
asymmetric GroEL:7ADP:GroES complex in the presence or absence of SP and is a
consequence of inter-ring negative allostery. We find that a GroEL mutant unable
to perform ring separation is folding active but populates symmetric GroEL:GroES2
complexes, where both GroEL rings function simultaneously rather than
sequentially. As a consequence, SP binding and release from the folding chamber
is inefficient, and E. coli growth is impaired. We suggest that transient ring
separation is an integral part of the chaperonin mechanism.
PMID- 29336890
TI - Some notes on citrulline in the CNS.
PMID- 29336889
TI - KRAS Dimerization Impacts MEK Inhibitor Sensitivity and Oncogenic Activity of
Mutant KRAS.
AB - The mechanism by which the wild-type KRAS allele imparts a growth inhibitory
effect to oncogenic KRAS in various cancers, including lung adenocarcinoma
(LUAD), is poorly understood. Here, using a genetically inducible model of KRAS
loss of heterozygosity (LOH), we show that KRAS dimerization mediates wild-type
KRAS-dependent fitness of human and murine KRAS mutant LUAD tumor cells and
underlies resistance to MEK inhibition. These effects are abrogated when wild
type KRAS is replaced by KRASD154Q, a mutant that disrupts dimerization at the
alpha4-alpha5 KRAS dimer interface without changing other fundamental biochemical
properties of KRAS, both in vitro and in vivo. Moreover, dimerization has a
critical role in the oncogenic activity of mutant KRAS. Our studies provide
mechanistic and biological insights into the role of KRAS dimerization and
highlight a role for disruption of dimerization as a therapeutic strategy for
KRAS mutant cancers.
PMID- 29336888
TI - LXR/ApoE Activation Restricts Innate Immune Suppression in Cancer.
AB - Therapeutic harnessing of adaptive immunity via checkpoint inhibition has
transformed the treatment of many cancers. Despite unprecedented long-term
responses, most patients do not respond to these therapies. Immunotherapy non
responders often harbor high levels of circulating myeloid-derived suppressor
cells (MDSCs)-an immunosuppressive innate cell population. Through genetic and
pharmacological approaches, we uncovered a pathway governing MDSC abundance in
multiple cancer types. Therapeutic liver-X nuclear receptor (LXR) agonism reduced
MDSC abundance in murine models and in patients treated in a first-in-human dose
escalation phase 1 trial. MDSC depletion was associated with activation of
cytotoxic T lymphocyte (CTL) responses in mice and patients. The LXR
transcriptional target ApoE mediated these effects in mice, where LXR/ApoE
activation therapy elicited robust anti-tumor responses and also enhanced T cell
activation during various immune-based therapies. We implicate the LXR/ApoE axis
in the regulation of innate immune suppression and as a target for enhancing the
efficacy of cancer immunotherapy in patients.
PMID- 29336891
TI - Cupuacu extract reduces nitrosative stress and modulates inflammatory mediators
in the kidneys of experimental diabetes.
AB - BACKGROUND & AIMS: We have previously reported an increased nitrosative stress in
the kidneys of diabetic animals, which was reduced by an antioxidant probiotic.
The present study evaluated whether the extract of cupuacu (EC), an antioxidant
compound rich in polyphenols and theograndins, when administered at a dose that
can be reasonably obtained through daily consumption, could delay the onset of
diabetic complications in the kidney. METHODS: Mouse immortalized mesangial cells
(MiMC) were placed in medium normal glucose (NG) or high glucose (HG), with or
without EC (500, 100, 50 or 10 MUg/mL) during 24, 48 or 72 h for analysis of
viability, proliferation, nitric oxide (NO) levels and reactive oxygen species or
nitrogen (ROS/RNS). Male, adult Wistar rats were distributed in 4 groups: control
(CTL) and diabetic (DM) who received water; CTLEC and DMEC who received 1 mL/day
of EC (1 g/mL), via gavage for 8 consecutive weeks. After, metabolic profile and
renal function were evaluated and, kidneys were collected for analysis of NO,
ROS, 3-nitrotyrosine (3-NT), endothelial nitric oxide synthase (eNOS), IL-6, IL
10, TNF-alpha and NF-kappaB p65. RESULTS: The MiMC showed normal viability in all
groups, demonstrating that EC had no cytotoxic effect at doses on 24, 48 or 72 h.
MiMC under HG presented significant increase in proliferation, NO and ROS vs. NG;
these parameters were significantly reduced after 72 h of EC treatment (P <
0.05). DMEC showed a significant reduction of feed intake, ROS and NO, 3-NT, IL-6
and eNOS vs. DM (P < 0.05). Supplementation with EC at a dose consumed daily
could improve control of nitrosative stress, combined with reduction of
inflammatory factors, suggesting the importance of bioactive compounds as non
pharmacological adjuvant therapy to delay kidney complications in diabetic
patients.
PMID- 29336892
TI - Gene therapy and gene editing strategies for hemoglobinopathies.
AB - Gene therapy for hemoglobinopathies is currently based on transplantation of
autologous hematopoietic stem cells genetically modified with an integrating
lentiviral vector expressing a globin gene under the control of globin
transcriptional regulatory elements. Studies and safety works demonstrated the
potential therapeutic efficacy and safety of this approach, providing the
rationale for clinical translation. The outcomes of early clinical trials,
although showing promising results, have highlighted the current limitations to a
more general application. These include the nature, source and age of
repopulating hematopoietic stem cells, the suboptimal transduction efficiency and
gene expression levels, the toxicity and efficacy of bone marrow conditioning,
the stress status of bone marrow microenvironment in chronic diseases such as
beta-thalassemia and sickle cell disease. Recently, gene editing strategies based
on the use of nucleases offered a novel approach to increase globin expression in
a quasi-physiological way, independently from the addition of transgenes and
viral sequences to the human genome. This review will discuss the current status
of gene therapy for beta-thalassemia and sickle cell disease with a perspective
towards the improvements necessary in the context of clinical translation.
PMID- 29336893
TI - A meta-analysis of the utility of the neutrophil-to-lymphocyte ratio in
predicting survival after pancreatic cancer resection.
AB - BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is thought to reflect cancer
disease burden. To assess the prognostic ability of the NLR on overall survival
in patients with resectable, pancreatic cancer a meta-analysis of published
literature was undertaken. METHOD: A systematic review was performed
independently by two authors using PubMed, Ovid MEDLINE and Embase databases.
Included studies detailed the pre-operative NLR and overall survival of
pancreatic cancer patients. RESULTS: Of the 214 studies retrieved using the
search strategy, 8 studies involving 1519 patients were included in the meta
analysis. Only one study did not find a statistically significant association
between a high NLR and OS. The pooled Hazard Ratio was 1.77 (95% CI [1.45-2.15];
p < 0.01). The NLR cut-off values ranged from 2 to 5. There was low to moderate
inter-study heterogeneity (I2 = 31%; p = 0.17), a low risk of intra-study bias,
and potentially 3 unpublished (negative) studies. CONCLUSIONS: A high pre
operative NLR indicates a worse prognosis than in patients with a low NLR. There
is potential to use the NLR to direct therapies. A specific cut-off value has not
been established from this study and so further research is required.
PMID- 29336894
TI - Preoperative surveillance rectal swab is associated with an increased risk of
infectious complications in pancreaticoduodenectomy and directs antimicrobial
prophylaxis: an antibiotic stewardship strategy?
AB - BACKGROUND: Despite improvements in the perioperative care, the morbidity rate
after pancreaticoduodenectomy (PD) is still higher than 50%. The aim of this
study was twofold: first, to assess the correlation between preoperative rectal
swab (RS) and intraoperative bile cultures; to examine the impact of RS isolates
on postoperative course after PD. METHODS: An observational study was conducted
analyzing all consecutive PD performed from January 2015 to July 2016. Based on
the positivity/negativity of preoperative RS for multi-drug resistant bacteria,
two groups of patients were identified (RS+ vs. RS-) and then compared. RESULTS:
Three hundred thirty-eight patients were considered for the analysis. RS culture
showed a perfect correlation (species and phenotypic antibiotic susceptibility
pattern) with bile culture in 157 patients (86.7%). Fifty patients (14.8%) had a
RS+. Preoperative biliary drain (PBD) was the single independent preoperative
risk factor associated to RS+ (p = 0.021, OR = 2.6, 95% CI = 1.5-11.7). Infective
complications (IC) and mortality were independently correlated to RS+ (p = 0.013,
OR = 2.9, 95% CI = 1.3-6.7; p = 0.009 OR = 3.4, 95% CI = 1.8-14.9, respectively).
CONCLUSIONS: Preoperative surveillance RS-culture's positivity correlates to
biliary colonization that occurs after PBD. IC and mortality after PD are
associated with RS+. Preoperative RS can direct antibiotic prophylaxis to reduce
morbidity and mortality after PD.
PMID- 29336895
TI - Alterations in peripheral fatty acid composition in bipolar and unipolar
depression.
AB - BACKGROUND: Lipid metabolism has been shown to play an important role in unipolar
and bipolar depression. In this study, we aimed to evaluate levels of fatty acids
in patients with unipolar (MDD) and bipolar depression (BDD) in comparison to
patients with bipolar disorder in euthymia (BDE) and non-psychiatric controls.
METHODS: Levels of saturated fatty acids (SFAs), monounsaturated fatty acids
(MUFAs) and polyunsaturated fatty acids (PUFAs) were assessed in serum of (87)
patients with BD (31 euthymic, 22 depressive) or MDD (34) and (31) non
psychiatric controls through GC-FID. RESULTS: No significant difference in total
levels of PUFAs (polyunsaturated fatty acids), SFAs (saturated fatty acids),
MUFAs (monounsaturated fatty acids) and total fatty acids were found between
groups. Our results demonstrated higher levels AA: EPA and AA: EPA+DHA in
patients with BDD. Additionally, we observed that overall omega-6 present a
positive correlation with illness duration in patients with BDD and AA: EPA ratio
positively associated with illness duration in MDD group. Depression severity was
positively associated with AA: EPA+DHA ratio in all participants. CONCLUSION:
Together, our results support the relevance for the balance of omega-3 and omega
6 in BDD. Also, our results suggest a potential subset of stage-related lipid
biomarkers that further studies are needed to help clarify the dynamics of lipid
alteration in BD and MDD.
PMID- 29336896
TI - Targeted Retinal Photocoagulation for Diabetic Macular Edema with Peripheral
Retinal Nonperfusion: Three-Year Randomized DAVE Trial.
AB - PURPOSE: To evaluate the effect of targeted retinal photocoagulation (TRP) on
visual and anatomic outcomes and treatment burden in eyes with diabetic macular
edema (DME). DESIGN: Phase I/II prospective, randomized, controlled clinical
trial. PARTICIPANTS: Forty eyes of 29 patients with center-involved macular edema
secondary to diabetes mellitus. METHODS: Eyes with center-involved DME and Early
Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA)
between 20/32 and 20/320 (Snellen equivalent) were randomized 1:1 to monotherapy
with 0.3 mg ranibizumab (Lucentis, Genentech, South San Francisco, CA) or
combination therapy with 0.3 mg ranibizumab and TRP guided by widefield
fluorescein angiography. All eyes received 4 monthly ranibizumab injections
followed by monthly examinations and pro re nata (PRN) re-treatment through 36
months. Targeted retinal photocoagulation was administered outside the macula to
areas of retinal capillary nonperfusion plus a 1-disc area margin in the
combination therapy arm at week 1, with re-treatment at months 6, 18, and 25, if
indicated. MAIN OUTCOME MEASURES: Mean change in ETDRS BCVA from baseline and
number of intravitreal injections administered. RESULTS: At baseline, mean age
was 55 years, mean BCVA was 20/63 (Snellen equivalent), and mean central retinal
subfield thickness (CRT) was 530 MUm. Thirty-four eyes (85%) completed month 36,
at which point mean BCVA improved 13.9 and 8.2 letters (P = 0.20) and mean CRT
improved 302 and 152 MUm (P = 0.03) in the monotherapy and combination therapy
arms, respectively. The mean number of injections administered through month 36
was 24.4 (range, 10-34) and 27.1 (range, 12-36), with 73% (362/496) and 80%
(433/538) of PRN injections administered (P = 0.004) in the monotherapy and
combination therapy arms, respectively. Goldmann visual field isopter III-4e area
decreased by 2% and 18% in the monotherapy and combination therapy arms,
respectively (P = 0.30). CONCLUSIONS: In this 3-year randomized trial of 40 eyes
with DME, there was no evidence that combination therapy with ranibizumab and TRP
improved visual outcomes or reduced treatment burden compared with ranibizumab
alone.
PMID- 29336897
TI - The Real-World Effect of Intravitreous Anti-Vascular Endothelial Growth Factor
Drugs on Intraocular Pressure: An Analysis Using the IRIS Registry.
AB - PURPOSE: To identify sustained differences in intraocular pressure (IOP) after
intravitreous injections of anti-vascular endothelial growth factor (VEGF) drugs.
DESIGN: Database study. PARTICIPANTS: Patients seeing an ophthalmic provider who
contributes to the database. METHODS: We identified a total of 23 776 unique
patients who received only a single type of anti-VEGF medication (bevacizumab,
aflibercept, or ranibizumab) by injection in the right eye in the American
Academy of Ophthalmology Intelligent Research in Sight Registry. Subgroups
included patients with age-related macular degeneration only and patients who had
not received an anti-VEGF injection for at least 1 year before the study. We
examined those with at least 12, 18, and 25 injections for each of these 3
medications. For all groups, we used fellow, untreated eyes for comparison. MAIN
OUTCOME MEASURES: The mean change in IOP from baseline at a minimum of 1 year of
follow-up and the proportion of eyes with a clinically significant IOP increase
(defined as sustained rise of at least 6 mmHg to an IOP of more than 21 mmHg).
RESULTS: All patients in all groups receiving all drugs showed a decrease in IOP
from baseline, with a mean of 0.9 mmHg in treated eyes compared with an average
decrease of 0.2 mmHg in fellow untreated eyes, a statistically significant
difference. A generalized linear model accounting for confounders associated
bevacizumab with slightly less lowering of IOP than aflibercept and ranibizumab
in most subgroups. A clinically significant IOP increase was seen in 2.6% of eyes
receiving injections compared with 1.5% in the associated untreated fellow eyes.
Clinically significant IOP increases occurred at a rate of 1.9%, 2.8%, and 2.8%
for aflibercept, ranibizumab, and bevacizumab, respectively, which was
significantly higher than untreated fellow eyes for bevacizumab and ranibizumab,
but not for aflibercept. CONCLUSIONS: These analyses from real-world data
indicate that anti-VEGF intravitreous injections are associated with a small but
statistically significant decrease in IOP over time. A proportion of patients, on
average 2.6%, experienced a sustained clinically significant IOP rise with these
drugs overall compared with 1.5% in the fellow untreated eyes. However, such an
increase was not seen with aflibercept.
PMID- 29336898
TI - Effect of transcranial direct current stimulation on short-term and long-term
treatment of chronic tinnitus.
AB - OBJECTIVE: This study was conducted to investigate the effectiveness of anodal
and cathodal methods in reducing the intensity of tinnitus and to compare them
with the control. METHODOLOGY: This randomized double-blind clinical trial with
case and control groups was conducted in Al-Zahra Hospital in Isfahan between
2015 and 2016. In this trial, 51 patients with tinnitus, for at least one year,
were selected among those outpatients visiting the throat, nose and ear clinic
within this period. Inclusion criteria were patients on electrical stimulation
prohibition, with Meniere's disease, otosclerosis, chronic headache, and
pulsatile tinnitus. Patients were randomly divided in three equal-sized groups:
anodal stimulation group, cathodal stimulation group, and control group. The
subjects received 20-min current stimulation (2 mA). Five subjects were selected
from those with a significant difference between the stimulated states (anodal or
cathodal) and/or control. They received weekly transcranial electrical
stimulation for two months, and their long-term recovery from tinnitus was
investigated. Data analysis was done with SPSS20. RESULTS: Findings showed no
significant between-groups difference in mean scores of tinnitus before the
intervention (p = .68); whereas, this difference was significant immediately
after the intervention (p = .02) and 1 h after it (p = .03). The mean score of
tinnitus in the anodal stimulation group was significantly lower than the
control; whereas, no significant difference was observed between the anodal and
cathodal stimulation groups, and between the cathodal and control groups (p <
.05). Findings also showed that the mean scores of tinnitus in two cathodal
stimulation groups (p = .24) and control group (p = .62) were not significantly
different at three different points of time; whereas, this score was
significantly different in the anodal group at these time points (p = .01).
CONCLUSION: In conclusion, anodal stimulation was more effective than the
cathodal and control stimulation in reducing the intensity of tinnitus in the
short term.
PMID- 29336899
TI - Commentary on letter to the editor on manuscript "Image analysis of
interarytenoid area to detect cases of Laryngopharyngeal Reflux: An objective
method".
PMID- 29336900
TI - Combined use of a nanocarbon suspension and 99mTc-MIBI for the intra-operative
localization of the parathyroid glands.
AB - OBJECTIVE: To investigate the combined use of a nanocarbon (NC) suspension and
low-dose 99mTc-MIBI for parathyroid localization during surgery in patients with
secondary hyperparathyroidism (sHPT). METHODS: Between March 2010 and September
2015, 40 patients with sHPT were enrolled in this study and were randomized to
receive either low-dose 99mTc-MIBI+NC (group I) or low-dose 99mTc-MIBI (group
II). Pre- and post-operative serum levels of intact PTH (iPTH), calcium and
phosphorus between groups were compared and the intra-operative radioactive
counts of the parathyroid glands were measured. RESULTS: The post-operative iPTH
level was significantly lower in patients of group I (24.2+/-31ng/L) than in
those of group II (106+/-155ng/L) (P=0.03) while there were no significant
differences in intra-operative parathyroid gland radioactive counts between the
groups. The duration of the surgical procedure was shorter for patients of group
I than patients of group II. There were no serious intra-operative or post
operative complications. CONCLUSION: The combined use of an NC suspension and
99mTc-MIBI for patients with sHPT is strongly recommended for the localization of
parathyroid glands during surgery and is likely to improve clinical outcomes for
patients.
PMID- 29336901
TI - Image analysis of the interarytenoid area to detect laryngopharyngeal reflux
disease.
PMID- 29336902
TI - Surgical management of pulsatile tinnitus secondary to jugular bulb or sigmoid
sinus diverticulum with review of literature.
AB - INTRODUCTION: Jugular bulb and sigmoid sinus anomalies are well-known causes of
vascular pulsatile tinnitus. Common anomalies reported in the literature include
high-riding and/or dehiscent jugular bulb, and sigmoid sinus dehiscence. However,
cases of pulsatile tinnitus due to diverticulosis of the jugular bulb or sigmoid
sinus are less commonly encountered, with the best management option yet to be
established. In particular, reports on surgical management of pulsatile tinnitus
caused by jugular bulb diverticulum have been lacking in the literature.
OBJECTIVES: To report two cases of pulsatile tinnitus with jugular bulb and/or
sigmoid sinus diverticulum, and their management strategies and outcomes. In this
series, we describe the first reported successful case of pulsatile tinnitus due
to jugular bulb diverticulum that was surgically-treated. SUBJECTS AND METHODS:
Two patients diagnosed with either jugular bulb and/or sigmoid sinus
diverticulum, who had presented to the Otolaryngology clinic with pulsatile
tinnitus between 2016 and 2017, were studied. Demographic and clinical data were
obtained, including their management details and clinical outcomes. RESULTS: Two
cases (one with jugular bulb diverticulum and one with both sigmoid sinus and
jugular bulb diverticula) underwent surgical intervention, and both had immediate
resolution of pulsatile tinnitus post-operatively. This was sustained at
subsequent follow-up visits at the outpatient clinic, and there were no major
complications encountered for both cases intra- and post-operatively. CONCLUSION:
Transmastoid reconstruction/resurfacing of jugular bulb and sigmoid sinus
diverticulum with/without obliteration of the diverticulum is a safe and
effective approach in the management of bothersome pulsatile tinnitus arising
from these causes.
PMID- 29336903
TI - One-year experience of a regional service model of teleconsultation for planning
and treatment of complex thoracoabdominal aortic disease.
AB - OBJECTIVE: The objective of this study was to report the methodology and 1-year
experience of a regional service model of teleconsultation for planning and
treatment of complex thoracoabdominal aortic disease (TAAD). METHODS: Complex
TAADs without a feasible conventional surgical repair were prospectively
evaluated by vascular surgeons of the same public health service (National Health
System) located in a huge area of 22,994 km2 with 3.7 million inhabitants and 11
tertiary hospitals. Surgeons evaluated computed tomography scans and clinical
details that were placed on a web platform (Google Drive; Google, Mountain View,
Calif) and shared by all surgeons. Patients gave informed consent for the
teleconsultation. The surgeon who submits a case discusses in detail his or her
case and proposes a possible therapeutic strategy. The other surgeons suggest
other solutions and options in terms of grafts, techniques, or access to be used.
Computed tomography angiography, angiography, and clinical outcomes of cases are
then presented at the following telemeetings, and a final agreement of the
operative strategy is evaluated. Teleconsultation is performed using a web
conference service (WebConference.com; Avaya Inc, Basking Ridge, NJ) every month.
An inter-rater agreement statistic was calculated, and the kappa value was
interpreted according to Altman's criteria for computed tomography angiography
measurements. RESULTS: The rate of participation was constant (mean number of
surgeons, 11; range, 9-15). Twenty-four complex TAAD cases were discussed for
planning and operation during the study period. The interobserver reliability
recorded was moderate (kappa = 0.41-0.60) to good (kappa = 0.61-0.80) for
measurements of proximal and distal sealing and very good (kappa = 0.81-1) for
detection of any target vessel angulation >60 degrees, significant calcification
(circumferential), and thrombus presence (>50%). The concordance for planning and
therapeutic strategy among all participants was complete in 16 cases. In one
case, the consultation was decisive for creating an innovative therapeutic
strategy; in the remaining seven cases, the strategy proposed by the patient's
surgeon was changed completely after the discussion. Technical success was the
same (100%) if concordance in planning was present initially or not. Overall 6
month mortality was 4%, 0% for those patients with initial concordance in
planning vs 12% for those without initial concordance (P = .33). Surgery was
always performed in a tertiary hospital by local surgeons, and in two cases (8%)
external surgeons joined the local surgical team. CONCLUSIONS: Such a regional
service of teleconsultation may be of value in standardizing the treatment and
derived costs of complex TAADs in a huge region under the same health provider.
The shared decision-making strategy may be of medical-legal value as well.
PMID- 29336905
TI - Getting a good night sleep? The importance of recognizing and treating nocturnal
hypokinesia in Parkinson's disease.
AB - When Parkinson's disease (PD) patients are asked about the quality of their
sleep, their answers are dominated by difficulties associated with impaired
mobility in bed, medically referred to as nocturnal hypokinesia. Nocturnal
hypokinesia is symptomatic from the mid-stage of the disease, affecting up to 70%
of PD patients, and contributes to poor sleep quality, and increased carer
burden. Here we explore four areas of nocturnal hypokinesia that are relevant to
clinical practice, namely: manifestations and definition; clinical assessment and
objective monitoring; etiologies and contributing factors; and evidence-based
therapeutic approaches. In addition, we provide an operational definition of what
constitutes nocturnal hypokinesia and outline different methods of assessment,
ranging from clinical interviews and rating scales to objective night-time
monitoring with inertial sensors. Optimal management of nocturnal hypokinesia in
PD begins with recognizing its manifestation by inquiring about cardinal symptoms
and contributing factors from, not only patients, but also carers, followed by
formal assessment, and the application of individualized evidence-based
treatment. Night-time dopaminergic treatment is the primary therapy; however,
careful clinical judgment is required to balance the benefits with the potential
adverse events related to nocturnal dopaminergic stimulation. Future studies are
needed to explore the practicality of home-based objective assessment of
nocturnal hypokinesia, new therapeutic options not limited to dopaminergic
medications, and non-pharmacologic approaches, including training on compensatory
strategies and bedroom adaptations.
PMID- 29336904
TI - Bypass versus endovascular intervention for healing ischemic foot wounds
secondary to tibial arterial disease.
AB - OBJECTIVE: Pedal (inframalleolar) bypass is a long-standing therapy for tibial
arterial disease in patients with ischemic tissue loss. Endovascular tibial
intervention is an appealing alternative with lower risks of perioperative
mortality or complications. Our objective was to compare the effectiveness of
these two treatment modalities with respect to patency and limb-related clinical
outcomes. METHODS: We performed a retrospective chart review of patients
presenting between 2006 and 2013 with ischemic foot wounds and infrapopliteal
arterial disease who underwent a revascularization procedure (either open
surgical bypass to an inframalleolar target or endovascular tibial intervention).
Data were collected on baseline demographics and comorbidities, procedural
details, and postprocedure outcomes. The primary outcome was successful healing
of the index wound, with mortality, major amputation, and patency assessed as
secondary outcomes. RESULTS: We identified 417 patients who met our eligibility
criteria; 105 underwent surgical bypass and 312 underwent endovascular
intervention, with mean follow-up of 25.0 and 20.2 months, respectively (P =
.08). The endovascular patients were older at baseline (P = .009), with higher
rates of hyperlipidemia (P = .02), prior cerebrovascular accidents (P = .04), and
smoking history (P = .04). Within 30 days postoperatively, there was no
difference in mortality (P = .31), but bypass patients had longer hospital length
of stay (P < .0001), higher rate of discharge to nursing facility (P < .001), and
higher rates of myocardial infarctions (P = .03) and wound complications (P <
.001). At 6 months, the rate of wound healing was 22.4% in the bypass group
compared with 29.0% in the endovascular group (P = .02). At 1 year, survival was
higher after bypass (86.2% vs 70.4%; P < .0001), but freedom from major
amputation was similar (84.9% vs 82.8%; P = .42). Primary patency (53.1% vs
38.2%; P = .002) and primary assisted patency (76.6% vs 51.7%; P < .0001) were
higher in the bypass group, but there was no difference in secondary patency
(77.3% vs 73.8%; P = .13). CONCLUSIONS: Endovascular tibial intervention is
associated with poorer primary patency but similar secondary patency and wound
healing rates compared with the "gold standard" of surgical bypass to a pedal
target. In patients with tibial arterial disease, endovascular intervention
should be considered a lower risk alternative to pedal bypass that provides
similar clinical outcomes.
PMID- 29336906
TI - Progression of white matter damage in progressive supranuclear palsy with
predominant parkinsonism.
AB - INTRODUCTION: Progressive supranuclear palsy with predominant parkinsonism (PSP
P) accounts for 14-35% of all PSP cases. A few cross-sectional MRI studies in PSP
P showed a remarkable white matter (WM) damage. Progression of brain structural
damage in these patients remains unknown. METHODS: Longitudinal clinical,
cognitive and diffusion tensor (DT) MRI data were obtained over a mean 1.6 year
follow up in 10 PSP-P patients. At study entry, patients were compared with 36
healthy controls. Voxelwise statistical analysis of white matter DT MRI data
(mean, axial and radial diffusivity, and fractional anisotropy) was carried out
using tract-based spatial statistics. RESULTS: During the 1.6 year follow up, PSP
P patients showed significant decline of motor, cognitive and mood disturbances.
DT MRI analysis revealed at baseline a widespread pattern of WM alterations. Over
time, PSP-P patients exhibited progression of WM damage in supratentorial tracts
compared to baseline. No WM changes were detected in cerebellar WM. CONCLUSIONS:
In PSP-P patients, WM damage significantly progressed over time. Longitudinal DT
MRI measures are a potential in vivo marker of disease progression in PSP-P.
PMID- 29336907
TI - A Palliative Approach to Falls in Advanced Dementia.
AB - Falls are viewed as a preventable cause of injury, functional loss, and death in
older adults with dementia, and have been used as a marker of quality of care in
long-term care facilities. Despite intensive intervention around fall prevention
in these settings, falls and injury remain frequent, particularly among residents
in the advanced stages of dementia. In this clinical review, we consider the
common challenges and pitfalls in both the management of falls and the provision
of palliative care in advanced dementia. We then describe a palliative approach
to falls in advanced dementia that involves identifying individuals who would
benefit from this care approach, framing falls and loss of mobility as a quality
of life issue, and devising an individualized symptom assessment and management
plan. A palliative approach can lead to recognition and acceptance that recurrent
falls are often symptomatic of advanced dementia, and that not all falls are
preventable. We conclude that falls in the advanced stage of dementia can be
sentinel events indicating the need for a palliative approach to care. Rather
than replace falls prevention activities, a palliative approach to falls prompts
us to select dementia stage-appropriate interventions with a focus on symptom
management, comfort, and dignity.
PMID- 29336908
TI - Re: Sentinel node biopsy in desmoplastic thin melanoma: Histogenetic
recommendations.
PMID- 29336909
TI - [Non reported spa types in our country in Staphylococcus aureus from adult
patients of a school hospital, Santa Fe - Argentina].
AB - Staphylococcus aureus is a pathogen associated a different kind of infection.
Molecular markers are useful tools to study microbial epidemiology. Twenty two
methicillin-resistant S. aureus (MRSA) and 23 methicillin-susceptible S. aureus
(MSSA) were studied by mecA gene, SCCmec cassette, Panton Valentine leucocidin
(PVL) and spa polymorphism. The clinical data patients were analyzed. MSSA was
prevalent in samples different from skin and soft tissue (SST) and in
hospitalized patients, whereas MRSA in SST. SCCmec type IV was predominant,
followed by type I. Low presence of PVL was found. In MRSA 11 different types of
spa were detected, t019 was the most frequent and associated with outpatient, 17
types were found in MSSA and t189 was prevalent. spa t002 was present in MSSA and
MRSA. We found 11 types of spa not reported in our country.
PMID- 29336910
TI - Bioconversion of hemicellulosic materials into ethanol by yeast, Pichia
kudriavzevii 2-KLP1, isolated from industrial waste.
AB - In the present work, a yeast strain Pichia kudriavzevii was identified on the
basis of 18S rDNA, showing maximum growth at 30 degrees C and pH 7.0. Among all
the complex polysaccharides used, wheat bran proved to be the best substrate as
indicated by the maximum growth of the yeast strain. The yeast isolate was
capable of producing xylanase both intra- and extra-cellularly, the dominant form
being extracellular. The maximum enzyme activity was determined at pH 5.0 and at
50 degrees C. Na+, Mg2+ and Fe2+ presence caused a substantial increase in enzyme
activity while a slight decrease (4.5%) was observed in the presence of Mn2+,
Zn2+ and Cu2+. Pyruvate decarboxylase (PDC) and alcohol dehydrogenase (ADH)
activities were assayed to confirm the presence of the ethanol pathway and PDC
activity was much more pronounced (73%) compared to ADH activity (51%). The yeast
strain can be employed to utilize hemicellulose containing agroindustrial
residues for ethanol production.
PMID- 29336911
TI - [Detection and characterization of Shiga toxin-producing Escherichia coli in
children treated at an inter-zonal pediatric hospital in the city of La Plata].
AB - Shiga toxin-producing Escherichia coli (STEC) is a foodborne pathogen that can
cause watery diarrhea, bloody diarrhea (BD), and hemolytic uremic syndrome (HUS).
The objective of this study was to determine the phenotypic and genotypic
profiles of STEC strains isolated from children with BD and HUS treated at a
pediatric hospital in the city of La Plata in the period 2006-2012, and to
establish the clonal relationship of O157:H7 isolates by pulsed field
electrophoresis. The percentage of positive samples was 4.9% and 39.2% in
patients with BD and HUS, respectively. Seventy-seven STEC strains from 10
different serotypes were isolated, with 100% colony recovery, O157:H7 being the
most frequent (71.4%) serotype, followed by O145:NM (15.6%). An average of 98.2%
of O157:H7 isolates belonged to biotype C and were sensitive to all the
antibiotics tested. All of them (100%) carried genotype stx2, eae, fliCH7, ehxA,
iha, efa, toxB, lpfA1-3 and lpfA2-2. When the clonal relationship of the O157:H7
strains was studied, a total of 42 patterns with at least 88% similarity were
identified, and 6 clusters with identical profiles were established. The eae
negative isolates belonged to serotypes O59:H19, O102:H6, O174:NM and O174:H21.
The strains O59:H19 and O174:H21 were positive for the aggR gene. This study
shows that STEC of different serotypes and genotypes circulate in the city of La
Plata and surroundings. Despite the genetic diversity observed between the
O157:H7 isolates, some were indistinguishable by the subtyping techniques used.
PMID- 29336912
TI - [Bartonella henselae: Serological evidence in pediatric patients with clinical
suspicion of cat scratch disease].
AB - Cat scratch disease (CSD) is caused by Bartonella henselae, which mainly affects
children. The cat is the reservoir. The laboratory diagnosis is based on the
detection of antibodies by the Indirect Immunofluorescence (IFI) assay. The
objective of this study was to analyze the serological evidence of B. henselae
infection in pediatric patients that met the clinical/epidemiological criteria
for suspected CSD. We studied 92 patients, who were categorized into four
serological groups: 1) IgG (+)/IgM(+), 31,5% (n=29); 2) IgG (-)/IgM(+), 10,9%
(n=10); 3) IgG (+)/IgM(-), 9,8% (n=9); 4) IgG (-)/IgM(-), 47,8% (n=44). These
findings aim to promote future works for investigating the seroprevalence of
Bartonella spp. in Argentina, which will allow us to know the importance of this
zoonosis in our population and to evaluate new cut-off points of the technique.
PMID- 29336913
TI - Erratum to "A systematic review of in-hospital worsening heart failure as an
endpoint in clinical investigations of therapy for acute heart failure" [Int. J.
Cardiol. 250 (2018) 215-222].
PMID- 29336915
TI - Stable coronary artery disease and endothelial progenitor cells.
PMID- 29336914
TI - Switching from clopidogrel to prasugrel to protect early invasive treatment in
acute coronary syndromes: Results of the switch over trial.
AB - BACKGROUND: Clopidogrel is used to pretreat patients with non-ST elevation acute
coronary syndromes (NSTE-ACS), but prasugrel provides better platelet inhibition
with improved outcome. However, switching from clopidogrel at the time of
percutaneous coronary intervention (PCI) remains incompletely defined. Our aim
was to compare the pharmacodynamic (PD) effects of 3 prasugrel loading doses
(LDs; G1:10mg, G2: 30mg, and G3: 60mg) before PCI. A fourth group, continuing
clopidogrel, served as control (G4). METHODS: 100 clopidogrel-pretreated patients
were enrolled and blood collected before PCI, 30min, 1, 2, 4, 6, 24 and 48h
thereafter. Platelet inhibition was measured by vasodilator-stimulated
phosphoprotein phosphorylation (VASP) and Verify-Now assays. The end-points (EP)
was the difference of PD effect at 4h between G3 and G4 (primary EP) with
hierarchic evaluation between G2 and G1 versus G4 (secondary EP). A mixed-design
ANOVA statistic was used to compare the four group scores over time. RESULTS:
Baseline characteristics were balanced across the groups. Only patients receiving
60 and 30mg prasugrel LDs showed a rapid (<1h) and significant (p<0.001) platelet
inhibition up to 48h after PCI.The primary EP was met by G3 (p<0.0001), but also
G2 scored different (p<0-001) from G4 at 4h after PCI. Similar findings were
observed with Verify-Now. No differences in 30-day clinical outcomes were
observed across groups. CONCLUSIONS: Switching NSTE-ACS patients before PCI to
prasugrel 60 or 30mg LDs determined a better and faster platelet inhibition than
continuing clopidogrel, while PCI it is still underway.
PMID- 29336916
TI - The outlook of prognostic indicators for the Takotsubo syndrome.
PMID- 29336917
TI - Changing Practice Evaluation-Stage 1 Seminoma: Outcomes With Adjuvant Treatment
Versus Surveillance: Risk Factors for Recurrence and Optimizing Follow-up
Protocols-Experience From a Supraregional Center.
AB - BACKGROUND: Stage 1 seminoma is frequently cured by radical orchiectomy; however,
the management strategies after this diagnosis vary in terms of the use of
adjuvant treatment and the nature of the follow-up protocols. We analyzed stage 1
seminomas treated in the Thames Valley Cancer Network for outcomes to determine
whether any factors are predictive of recurrence. We also studied relapses to
determine the optimal follow-up schedule and protocol. MATERIALS AND METHODS:
Data were obtained from centers within the Thames Valley Cancer Network for a 12
year period from 2004 to 2016. We identified 501 patients with stage 1 seminoma.
RESULTS: Relapses occurred in 6.2% of the patients receiving adjuvant treatment
and 6.1% of those who did not. The only statistically significant predictive
factor identified for relapse was rete testis invasion, and the risk was greater
when only stromal rete invasion was included, rather than pagetoid as well. A
trend was seen toward an increased risk with increased tumor size, but the
difference was not statistically significant. Recurrences developed within the
first 2 years after surgery in nearly 75% of cases and were identified through
surveillance computed tomography scans in 54.8% of the patients. All relapses
were treated curatively. CONCLUSION: Active surveillance leads to excellent
outcomes for stage 1 seminoma; however, adjuvant treatment should be reserved for
those with high-risk disease. Follow-up schedules should include computed
tomography imaging during the first 3 years, long-term measurement of tumor
markers, and mechanisms for patients to be seen promptly should symptoms of tumor
recurrence occur.
PMID- 29336918
TI - Current prevention and control of health care-associated infections in long-term
care facilities for the elderly in Japan.
AB - Residents of long-term care facilities for the elderly are vulnerable to health
care-associated infections. However, compared to medical institutions, long-term
care facilities for the elderly lag behind in health care-associated infection
control and prevention. We conducted a epidemiologic study to clarify the current
status of infection control in long-term care facilities for the elderly in
Japan. A questionnaire survey on the aspects of infection prevention and control
was developed according to SHEA/APIC guidelines and was distributed to 617 long
term care facilities for the elderly in the province of Osaka during November
2016 and January 2017. The response rate was 16.9%. The incidence rates of health
care-associated infection outbreaks and residents with health care-associated
infections were 23.4 per 100 facility-years and 0.18 per 1,000 resident-days,
respectively. Influenza and acute gastroenteritis were reported most frequently.
Active surveillance to identify the carrier of multiple drug-resistant organisms
was not common. The overall compliance with 21 items selected from the SHEA/APIC
guidelines was approximately 79.2%. All facilities had infection control manuals
and an assigned infection control professional. The economic burdens of infection
control were approximately US$ 182.6 per resident-year during fiscal year 2015.
Importantly, these data implied that physicians and nurses were actively
contributed to higher SHEA/APIC guideline compliance rates and the advancement of
infection control measures in long-term care facilities for the elderly. Key
factors are discussed to further improve the infection control in long-term care
facilities for the elderly, particularly from economic and social structural
standpoints.
PMID- 29336919
TI - Achalasia subtype differences based on clinical symptoms, radiographic findings,
and stasis scores.
PMID- 29336920
TI - Pediatric Nurse Practitioners' Perspectives on Health Care Transition From
Pediatric to Adult Care.
AB - INTRODUCTION: This study examined the perspectives of pediatric nurse
practitioners (PNPs) regarding the needs of adolescents, parents/caregivers,
clinicians, and institutions in the health care transition (HCT) process for
adolescents/young adults. METHODS: PNPs (N = 170) participated in a luncheon for
those interested in transition at an annual conference. Small groups discussed
and recorded their perspectives related to health care transition from adolescent
to adult services. Content analysis was used to analyze responses (Krippendorff,
2013). RESULTS: Four themes, Education, Health care system, Support, and
Communication, emerged from the data analysis. PNPs identified health care
informatics and adolescents' use of technology as additional critical aspects to
be considered in health care transition. DISCUSSION: Opportunities and challenges
identified by the PNPs are discussed to improve the quality and process of
transitioning adolescents to adult services. This report will help National
Association of Pediatric Nurse Practitioners formulate a new Health Care
Transition Policy Statement for the organization.
PMID- 29336921
TI - Legal and Policy Issues for LGBT Patients with Cancer or at Elevated Risk of
Cancer.
AB - OBJECTIVE: To understand the major legal and policy issues for lesbian, gay,
bisexual and transgender (LGBT) cancer patients. DATA SOURCES: LGBT health policy
research. CONCLUSION: Major policy issues include discrimination, lack of
cultural competency and clinically appropriate care, insurance coverage, family
recognition, and sexual orientation and gender identity data collection.
IMPLICATIONS FOR NURSING PRACTICE: Nurses play a major role in providing
affirming and competent care to LGBT cancer patients. Using correct names and
pronouns with transgender patients, and collecting sexual orientation and gender
identity data can send an affirming message to LGBT patients, as well as inform
decision support and preventive screenings, and improve treatment outcomes.
PMID- 29336922
TI - Segmentation-free direct tumor volume and metabolic activity estimation from PET
scans.
AB - Tumor volume and metabolic activity are two robust imaging biomarkers for
predicting early therapy response in F-fluorodeoxyglucose (FDG) positron emission
tomography (PET), which is a modality to image the distribution of radiotracers
and thereby observe functional processes in the body. To date, estimation of
these two biomarkers requires a lesion segmentation step. While the segmentation
methods requiring extensive user interaction have obvious limitations in terms of
time and reproducibility, automatically estimating activity from segmentation,
which involves integrating intensity values over the volume is also suboptimal,
since PET is an inherently noisy modality. Although many semi-automatic
segmentation based methods have been developed, in this paper, we introduce a
method which completely eliminates the segmentation step and directly estimates
the volume and activity of the lesions. We trained two parallel ensemble models
using locally extracted 3D patches from phantom images to estimate the activity
and volume, which are derivatives of other important quantification metrics such
as standardized uptake value (SUV) and total lesion glycolysis (TLG). For
validation, we used 54 clinical images from the QIN Head and Neck collection on
The Cancer Imaging Archive, as well as a set of 55 PET scans of the Elliptical
Lung-Spine Body PhantomTMwith different levels of noise, four different
reconstruction methods, and three different background activities, namely; air,
water, and hot background. In the validation on phantom images, we achieved
relative absolute error (RAE) of 5.11 % +/-3.5% and 5.7 % +/-5.25% for volume and
activity estimation, respectively, which represents improvements of over 20% and
6% respectively, compared with the best competing methods. From the validation
performed using clinical images, we found that the proposed method is capable of
obtaining almost the same level of agreement with a group of trained experts, as
a single trained expert is, indicating that the method has the potential to be a
useful tool in clinical practice.
PMID- 29336924
TI - Immunization of preterm infants with GSK's hexavalent combined diphtheria-tetanus
acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae
type b conjugate vaccine: A review of safety and immunogenicity.
AB - BACKGROUND: Infants with history of prematurity (<37 weeks gestation) and low
birth weight (LBW, <2500 g) are at high risk of infection due to functional
immaturity of normal physical and immunological defense mechanisms. Despite
current recommendations that infants with history of prematurity/LBW should
receive routine immunization according to the same schedule and chronological age
as full-term infants, immunization is often delayed. METHODS: Here we summarize
10 clinical studies and 15 years of post-marketing safety surveillance of GSK's
hexavalent vaccine (DTPa-HBV-IPV/Hib), a combined diphtheria-tetanus-acellular
pertussis-hepatitis-B-inactivated-poliovirus-Haemophilus influenzae-type-b (Hib)
conjugate vaccine, when administered alone, or co-administered with pneumococcal
conjugate, rotavirus, and meningococcal vaccines and respiratory syncytial virus
IgG to infants with history of prematurity/LBW in clinical trials. RESULTS: At
least 92.5% of infants with history of prematurity/LBW as young as 24 weeks
gestation in clinical studies were seropositive to all vaccine antigens after 3
dose primary vaccination with GSK's hexavalent DTPa-HBV-IPV/Hib vaccine, with
robust immune responses to booster vaccination. Seropositivity rates and antibody
concentrations to hepatitis B and Hib appeared lower in infants with history of
prematurity/LBW than term infants. Between 13-30% of medically stable infants
with history of prematurity developed apnea after vaccination with GSK's
hexavalent DTPa-HBV-IPV/Hib vaccine; usually after dose 1. The occurrence of post
immunization cardiorespiratory events appears to be influenced by the severity of
any underlying neonatal condition. Most cardiorespiratory events resolve
spontaneously or require minimal intervention. GSK's hexavalent DTPa-HBV-IPV/Hib
vaccine was well tolerated in co-administration regimens. CONCLUSION: GSK's
hexavalent DTPa-HBV-IPV/Hib vaccine alone or co-administered with other pediatric
vaccines has a clinically acceptable safety and immunogenicity profile when used
in infants with history of prematurity/LBW for primary and booster vaccination.
Additional studies are needed in very premature and very LBW infants. However,
currently available data support using GSK's hexavalent DTPa-HBV-IPV/Hib vaccine
to immunize infants with history of prematurity/LBW according to chronological
age.
PMID- 29336923
TI - Report on WHO meeting on immunization in older adults: Geneva, Switzerland, 22-23
March 2017.
AB - Many industrialized countries have implemented routine immunization policies for
older adults, but similar strategies have not been widely implemented in low- and
middle-income countries (LMICs). In March 2017, the World Health Organization
(WHO) convened a meeting to identify policies and activities to promote access to
vaccination of older adults, specifically in LMICs. Participants included
academic and industry researchers, funders, civil society organizations,
implementers of global health interventions, and stakeholders from developing
countries with adult immunization needs. These experts reviewed vaccine
performance in older adults, the anticipated impact of adult vaccination
programs, and the challenges and opportunities of building or strengthening an
adult and older adult immunization platforms. Key conclusions of the meeting were
that there is a need for discussion of new opportunities for vaccination of all
adults as well as for vaccination of older adults, as reflected in the recent
shift by WHO to a life-course approach to immunization; that immunization in
adults should be viewed in the context of a much broader model based on an
individual's abilities rather than chronological age; and that immunization
beyond infancy is a global priority that can be successfully integrated with
other interventions to promote healthy ageing. As WHO is looking ahead to a
global Decade of Healthy Ageing starting in 2020, it will seek to define a
roadmap for interdisciplinary collaborations to integrate immunization with
improving access to preventive and other healthcare interventions for adults
worldwide.
PMID- 29336926
TI - Changes of Tumour-Node-Metastasis Staging in 2017: Concepts and Evolutions in the
European and American Continents.
PMID- 29336925
TI - A novel inactivated vaccine against Lawsonia intracellularis induces rapid
induction of humoral immunity, reduction of bacterial shedding and provides
robust gut barrier function.
AB - Porcine proliferative ileitis is a major economic burden for the swine industry,
affecting growing pigs and young adult pigs. In this study, the protective
efficacy of an inactivated, injectable whole-cell bacteria vaccine against L.
intracellularis - Porcilis(r) Ileitis was evaluated under field conditions.
Eighty-five, three-week-old pigs on a commercial farrow-to-finish farm were
vaccinated by the intramuscular route, either with a dose of injectable vaccine,
or with saline. A subset of vaccinates and control pigs were necropsied at 21
days post-challenge. Incidence and severity of ileitis were evaluated by gross
and microscopic observation of ileal tissues. Colonization of the gut after
challenge was examined by L. intracellularis-specific immunohistochemistry, and
qPCR of ileal scrapings. Integrity of the intestinal barrier was evaluated to
quantify a range of intestinal markers including secreted mucin and intestinal
alkaline phosphatase, and innate immune markers including Caspase-3 and
Calprotectin. A second subset of pigs was monitored for fecal shedding of L.
intracellularis, until resolution of shedding. Our investigation indicated that
Porcilis Ileitis provided robust protection against ileitis, reduced bacterial
shedding 15-fold (p < .05) and preserved normal gut barrier function in the face
of an experimental challenge with virulent L. intracellularis.
PMID- 29336927
TI - Efficacy and Safety of Sacral and Percutaneous Tibial Neuromodulation in Non
neurogenic Lower Urinary Tract Dysfunction and Chronic Pelvic Pain: A Systematic
Review of the Literature.
AB - CONTEXT: Neuromodulation is considered in patients with non-neurogenic lower
urinary tract dysfunction (LUTD) not responsive to conservative treatment.
OBJECTIVE: To systematically review the available studies on efficacy and safety
of sacral neuromodulation (SNM) and percutaneous tibial nerve stimulation (PTNS)
in non-neurogenic LUTDs not responsive to conservative treatments. EVIDENCE
ACQUISITION: A literature research was conducted in PubMed/Medline and Scopus,
restricted to articles in English, published between January 1998 and June 2017,
with at least 20 patients and 6 mo of follow-up. EVIDENCE SYNTHESIS: Twenty-one
reports were identified. Concerning SNM, the improvement of >=50% in leakage
episodes ranged widely between 29% and 76%. Overall dry rate ranged between 43%
and 56%. Overall success/improvement rate in PTNS varied between 54% and 59%.
Symptom improvement or efficacy in interstitial cystitis/bladder pain syndrome
patients appeared to be lower compared with other indications in both techniques.
Safety data showed fewer side effects in patients submitted to PTNS. CONCLUSIONS:
Neuromodulation gives good results and is a safe therapy for patients with
overactive bladder or chronic nonobstructive urinary retention with long-lasting
efficacy. Moreover, PTNS has been shown to have good success rates and fewer side
effects compared with SNM. These data have to be confirmed with long-term follow
up. PATIENT SUMMARY: Sacral neuromodulation can improve low urinary tract
symptoms in selected patients; it appears to be a safe therapy for nonresponders
to standard medical therapies. Percutaneous tibial nerve stimulation (PTNS) is a
less invasive technique that gives good results in short time with fewer side
effects. However, we must consider that PTNS has not been tested in the long term
and results are lower if compared with SNM.
PMID- 29336928
TI - Tackling the recurrence of Clostridium difficile infection.
AB - The pathogenesis of recurrent Clostridium difficile infection (CDI) is still
poorly understood. The risk of recurrence is approximately 20% after an initial
CDI episode and dramatically increases with subsequent CDI recurrences. Several
factors may play a role in recurrent CDI (rCDI), including conditions influencing
germination, metabolic pathways that influence toxin production of C. difficile,
and the microbiota composition offering protection against colonization and
disease caused by C. difficile. Paradoxically, the currently recommended
treatment for acute symptomatic CDI, i.e. metronidazole or vancomycin, can cause
modification of the intestinal flora. Indeed, administration of anti-CDI
antibiotics leads to suppression of C. difficile, along with collateral damage of
the protective intestinal microbiota and opening of a "window of vulnerability"
for recurrence. Host factors also have a prominent role, including innate and
acquired humoral immunity, i.e. passive antibodies administration or active
vaccination as a prevention strategy. They play a crucial role in the protection
against severe and recurrent CDI. The assessment of risk factors of recurrence
and modeling prediction scores could help in preventing the troublesome
experience of CDI recurrence. Six studies have methodologically assessed
prediction scores for rCDI. However, the definition of recurrence was
heterogeneous, external validation was often not performed, and immunological
factors were often not considered. There is a need for further studies on the
pathophysiology of recurrence to design models for prediction that are sound and
applicable in clinical practice.
PMID- 29336929
TI - Economic burden and cost-effective management of Clostridium difficile
infections.
AB - Clostridium difficile infection (CDI) is the most important cause of healthcare
associated infectious diarrhea in industrialized countries. We performed a
literature review of the overall economic burden of initial and recurrent CDI as
well as of the cost-effectiveness of the various treatment strategies applied in
these settings. Even though analysis of health economic data is complicated by
the limited comparability of results, our review identified several
internationally consistent results. Authors from different countries have shown
that recurrent CDI disproportionally contributes to the overall economic burden
of CDI and therefore offers considerable saving potential. Subsequent cost
effectiveness analyses almost exclusively identified fidaxomicin as the preferred
treatment option for initial CDI and fecal microbiota transplant (FMT) for
recurrent CDI. Among the various FMT protocols, optimum results were obtained
using early colonoscopy-based FMT.
PMID- 29336930
TI - Exploring ways to improve CDI outcomes.
AB - Clostridium difficile is an anaerobic spore-forming Gram-positive bacillus
recognized as an evolving international health problem. Metronidazole and
vancomycin were - until recently - the only drugs available to treat C. difficile
infection (CDI). Better knowledge of the pathophysiology and the development of
new drugs completely modified the management of initial episodes and recurrences
of CDI. Fidaxomicin significantly reduced recurrences compared with vancomycin.
New drugs are also currently evaluated (cadazolid, surotomycin, ridinilazole,
rifaximin). Gut microbiota homeostasis was clearly shown to be a key determinant
in recurrences as demonstrated by the development of gut microbiota
transplantation and alternative microbiota substitution. Passive immunotherapy
and vaccinal approaches are also currently being evaluated. In conclusion, CDI
treatment has evolved with the development of new therapeutic pathways which now
need to be implemented in international guidelines.
PMID- 29336931
TI - Impact of crack cocaine use on the occurrence of oral lesions and micronuclei.
AB - The aim of this study was to investigate the occurrence of oral lesions and
micronuclei in crack cocaine users. A cross-sectional study was conducted
involving 106 crack users and 106 non-users matched for age, sex, and tobacco
use. Socio-demographic characteristics, the consumption of psychoactive
substances, and the occurrence of fundamental lesions were investigated. Cellular
changes in the oral mucosa (karyolysis, karyorrhexis, 'broken egg' events, and
micronuclei) were determined by exfoliative cytology for 54 participants in each
group. Crack users had a greater occurrence of fundamental lesions (P=0.001).
Furthermore, they had higher mean occurrences of micronuclei (17.25 vs. 3.80),
karyolysis (12.39 vs. 9.46), and karyorrhexis (30.39 vs. 10.11) (number per 1000
cells) than non-users (all P<0.05). No difference between the groups was found
with regard to broken egg events (P>0.05). After controlling for confounding
variables, fundamental lesions were 2.02-fold more frequent and micronuclei were
3.54-fold more frequent in crack users. Crack use was found to be associated with
clinical and cellular changes in the oral mucosa. These findings can contribute
to the planning of health care for individuals who are dependent on street drugs.
PMID- 29336932
TI - Orthognathic surgery in Melnick-Needles syndrome: a review of the literature and
report of two siblings.
AB - Melnick-Needles syndrome (MNS) is a rare congenital X-linked dominant skeletal
dysplasia, characterized by exophthalmos, a prominent forehead, and mandibular
hypoplasia and retrognathism. Dental features may include anodontia, hypodontia,
or oligodontia. Increased collagen content, unpredictable collagen synthesis, and
abnormal bony architecture have raised concerns regarding bone splitting
intraoperatively and bone healing postoperatively. This report describes the
cases of two sisters with MNS, who successfully underwent orthognathic surgery
consisting of bilateral mandibular ramus osteotomies combined with advancement
genioplasty and iliac crest bone grafting, to correct the classical MNS facial
deformity of mandibular retrognathia.
PMID- 29336933
TI - Left vocal cord paralysis after patent ductus arteriosus ligation: A systematic
review.
AB - CONTEXT: Extremely premature (EP) infants are at increased risk of left vocal
cord paralysis (LVCP) following surgery for patent ductus arteriosus (PDA).
OBJECTIVE: A Systematical Review was conducted to investigate the incidence and
outcomes of LVCP after PDA ligation in EP born infants. DATA SOURCES: Searches
were performed in Cochrane, Medline, Embase, Cinahl and PsycInfo. STUDY
SELECTION: Studies describing EP infants undergoing PDA surgery and reporting
incidence of LVCP were included. DATA EXTRACTION AND SYNTHESIS: Study details,
demographics, incidence of LVCP, diagnostic method and reported outcomes were
extracted. DerSimonian and Laird random effect models with inverse variance
weighting were used for all analyses. STUDY APPRAISAL: The Newcastle-Ottawa scale
for observational studies was used for quality assessment. RESULTS: 21
publications including 2067 infants were studied. The overall pooled summary
estimate of LVCP incidence was 9.0% (95% CI 5.0, 15.0). However, the pooled
incidence increased to 32% when only infants examined with laryngoscopy were
included. The overall risk ratio for negative outcomes was higher in the LVCP
group (2.20, 95% CI 1.69, 2.88, p = 0.01) compared to the non-LVCP-group.
CONCLUSIONS: Reported incidence of LVCP varies widely. This may be explained by
differences in study designs and lack of routine vocal cords postoperative
assessment. LVCP is associated with negative outcomes in EP infants. The
understanding of long-term outcomes is scarce. Routine laryngoscopy may be
necessary to identify all cases of LVCP, and to provide correct handling for
infants with LVCP.
PMID- 29336934
TI - Determination of recombination and polarity correction factors, kS and kP, for
small cylindrical ionization chambers PTW 31021 and PTW 31022 in pulsed filtered
and unfiltered beams.
AB - The aim of this technical communication is to provide correction factors for
recombination and polarity effect for two new ionization chambers PTW PinPoint 3D
(type 31022) and PTW Semiflex 3D (type 31021). The correction factors provided
are for the (based on the) German DIN 6800-2 dosimetry protocol and the AAPM TG51
protocol. The measurements were made in filtered and unfiltered high-energy
photon beams in a water equivalent phantom at maximum depth of the PDD and a
field size on the surface of 10cm*10cm. The design of the new chamber types leads
to an ion collection efficiency and a polarity effect that are well within the
specifications requested by pertinent dosimetry protocols including the addendum
of TG-51. It was confirmed that the recombination effect of both chambers mainly
depends on dose per pulse and is independent of the filtration of the photon
beam.
PMID- 29336935
TI - Update on the laboratory investigation of dyslipidemias.
AB - The role of the clinical laboratory is evolving to provide more information to
clinicians to assess cardiovascular disease (CVD) risk and target therapy more
effectively. Current routine methods to measure LDL-cholesterol (LDL-C), the
Friedewald calculation, ultracentrifugation, electrophoresis and homogeneous
direct methods have established limitations. Studies suggest that LDL and HDL
size or particle concentration are alternative methods to predict future CVD
risk. At this time there is no consensus role for lipoprotein particle or
subclasses in CVD risk assessment. LDL and HDL particle concentration are
measured by several methods, namely gradient gel electrophoresis,
ultracentrifugation-vertical auto profile, nuclear magnetic resonance and ion
mobility. It has been suggested that HDL functional assays may be better
predictors of CVD risk. To assess the issue of lipoprotein subclasses/particles
and HDL function as potential CVD risk markers robust, simple, validated
analytical methods are required. In patients with small dense LDL particles, even
a perfect measure of LDL-C will not reflect LDL particle concentration. Non-HDL-C
is an alternative measurement and includes VLDL and CM remnant cholesterol and
LDL-C. However, apolipoprotein B measurement may more accurately reflect LDL
particle numbers. Non-fasting lipid measurements have many practical advantages.
Defining thresholds for treatment with new measurements of CVD risk remain a
challenge. In families with genetic variants, ApoCIII and lipoprotein (a) may be
additional risk factors. Recognition of familial causes of dyslipidemias and
diagnosis in childhood will result in early treatment. This review discusses the
limitations in current laboratory technologies to predict CVD risk and reviews
the evidence for emergent approaches using newer biomarkers in clinical practice.
PMID- 29336936
TI - Very unusual "needle- and pencil-like" uric acid crystals in the urine unmasked
by infrared spectroscopy investigation.
AB - In this paper we describe a case with very unusual "needle- and pencil-like"
crystals, partly similar to those reported by other investigators, who considered
them as due to uric acid. Quite importantly, infrared spectroscopy investigation
which, to our knowledge, we have been the first to perform on this type of
crystals, confirmed their nature as uric acid structures. This case demonstrates
that the planet of urinary crystals still has several unknown facets and still
deserves exploration.
PMID- 29336937
TI - The combination of stereo-EEG and radiofrequency ablation.
AB - SEEG-guided radiofrequency thermocoagulation (SEEG-guided RFTC), a combination of
Stereo-electroencephalography (SEEG) and radiofrequency thermocoagulation (RFTC),
has been performed since 2001 in drug resistant epilepsy. The interest of this
procedure is to aim at total or partial destruction of the epileptogenic zone, as
tailored in each individual patient by the SEEG exploration. These multiple SEEG
guided RFTC lesions of epileptic foci are produced by using a radiofrequency
generator connected to the electrode contacts. This review summarizes the results
of SEEG-guided RFTC reported in 251 patients. This procedure appears to be safe
since complications are rare, minor and usually reversible, which is explained by
the use of functional electrical stimulations before RFTC. It makes it also
possible to produce RF lesions located very close to cortical areas having a high
functional value or being poorly accessible to a conventional surgical procedure.
Even if seizure outcome is not as good as results of surgery, 41% of the patients
are responders at 12 months with several seizure free patients. The benefit-risk
ratio of the SEEG-guided RFTC procedure proved to be particularly favorable for
the patients presenting with epileptogenic cortical malformation of development
(nodular heterotopy as well as focal cortical dysplasia) and for those in whom
surgery is not feasible or risky. For the patients in whom surgery is feasible,
SEEG-guided RFTC could be used as a first step, as a predictive therapeutic test
before resective surgery.
PMID- 29336938
TI - Determination of the energy requirements in mechanically ventilated critically
ill elderly patients in different BMI groups using the Harris-Benedict equation.
AB - BACKGROUND: Due to studies on calorie requirement in mechanically ventilated
critically ill elderly patients are few, and indirect calorimetry (IC) is not
available in every intensive care unit (ICU). The aim of this study was to
compare IC and Harris-Benedict (HB) predictive equation in different BMI groups.
METHODS: A total of 177 mechanically ventilated critically ill elderly patients
(?65 years old) underwent IC for measured resting energy expenditure (MREE).
Estimated calorie requirement was calculated by the HB equation, using actual
body weight (ABW) and ideal body weight (IBW) separately. Patients were divided
into four BMI groups. One-way ANOVA and Pearson's correlation coefficient were
used for statistical analyses. RESULTS: The mean MREE was 1443.6 +/- 318.2
kcal/day, HB(ABW) was 1110.9 +/- 177.0 kcal/day and HB(IBW) was 1101.5 +/- 113.1
kcal/day. The stress factor (SFA = MREE / HB(ABW)) was 1.43 +/- 0.26 for the
underweight, 1.30 +/- 0.27 for the normal weight, 1.20 +/- 0.19 for the
overweight, and 1.20 +/- 0.31 for the obese. The SFI (SFI = MREE / HB(IBW)) was
1.24 +/- 0.24 for the underweight, 1.31 +/- 0.26 for the normal weight, 1.36 +/-
0.21 for the overweight, and 1.52 +/- 0.39 for the obese. MREE had significant
correlation both with REE(ABW) = HB(ABW) * SFA (r = 0.46; P < 0.0001) and
REE(IBW) = HB(IBW) * SFI (r = 0.43; P < 0.0001). CONCLUSION: IC is the best
accurate method for assessing calorie requirement of mechanically ventilated
critically ill elderly patients. When IC is not available, using the predictive
HB equation is an alternative choice. Calorie requirement can be predicted by
HB(ABW) * 1.20-1.43 for critically ill elderly patients according to different
BMI groups, or using HB(IBW) * 1.24-1.52 for patients with edema, ascites or no
available body weight data.
PMID- 29336939
TI - Examination of serum hematinics and autoantibodies is important for treatment of
recurrent aphthous stomatitis.
PMID- 29336940
TI - Myeloperoxidase: Its role for host defense, inflammation, and neutrophil
function.
AB - Myeloperoxidase (MPO) is a heme-containing peroxidase expressed mainly in
neutrophils and to a lesser degree in monocytes. In the presence of hydrogen
peroxide and halides, MPO catalyzes the formation of reactive oxygen
intermediates, including hypochlorous acid (HOCl). The MPO/HOCl system plays an
important role in microbial killing by neutrophils. In addition, MPO has been
demonstrated to be a local mediator of tissue damage and the resulting
inflammation in various inflammatory diseases. These findings have implicated MPO
as an important therapeutic target in the treatment of inflammatory conditions.
In contrast to its injurious effects at sites of inflammation, recent studies
using animal models of various inflammatory diseases have demonstrated that MPO
deficiency results in the exaggeration of inflammatory response, and that it
affects neutrophil functions including cytokine production. Given these diverse
effects, a growing interest has emerged in the role of this well-studied enzyme
in health and disease.
PMID- 29336941
TI - Age-specific excess mortality patterns and transmissibility during the 1889-1890
influenza pandemic in Madrid, Spain.
AB - PURPOSE: Although the 1889-1890 influenza pandemic was one of the most important
epidemic events of the 19th century, little is known about the mortality impact
of this pandemic based on detailed respiratory mortality data sets. METHODS: We
estimated excess mortality rates for the 1889-1890 pandemic in Madrid from high
resolution respiratory and all-cause individual-level mortality data retrieved
from the Gazeta de Madrid, the Official Bulletin of the Spanish government. We
also generated estimates of the reproduction number from the early growth phase
of the pandemic. RESULTS: The main pandemic wave in Madrid was evident from
respiratory and all-cause mortality rates during the winter of 1889-1890. Our
estimates of excess mortality for this pandemic were 58.3 per 10,000 for all
cause mortality and 44.5 per 10,000 for respiratory mortality. Age-specific
excess mortality rates displayed a J-shape pattern, with school children aged 5
14 years experiencing the lowest respiratory excess death rates (8.8 excess
respiratory deaths per 10,000), whereas older populations aged greater than or
equal to 70 years had the highest rates (367.9 per 10,000). Although seniors
experienced the highest absolute excess death rates, the standardized mortality
ratio was highest among young adults aged 15-24 years. The early growth phase of
the pandemic displayed dynamics consistent with an exponentially growing
transmission process. Using the generalized-growth method, we estimated the
reproduction number in the range of 1.2-1.3 assuming a 3-day mean generation
interval and of 1.3-1.5 assuming a 4-day mean generation interval. CONCLUSIONS:
Our study adds to our understanding of the mortality impact and transmissibility
of the 1889-1890 influenza pandemic using detailed individual-level mortality
data sets. More quantitative studies are needed to quantify the variability of
the mortality impact of this understudied pandemic at regional and global scales.
PMID- 29336942
TI - Malleable Penile Implant Is an Effective Therapeutic Option in Men With
Peyronie's Disease and Erectile Dysfunction.
AB - BACKGROUND: The inflatable penile prosthesis (IPP) is typically the preferred
implant for Peyronie's disease (PD) and malleable penile prostheses (MPPs) have
been discouraged. AIMS: To evaluate the effectiveness and patient satisfaction of
the MPP vs IPP in patients with PD. METHODS: Men with PD and erectile dysfunction
who elected for penile implant surgery constituted the study population.
Preoperatively, demographic and comorbidity parameters were recorded. Curvature
was measured with a goniometer at maximum rigidity after intracavernosal
injection of a vasoactive agent. Postoperatively, overall satisfaction was
measured at 3, 6, 12, and 24 months on 5-point Likert scale from 1 (dissatisfied)
to 5 (very satisfied). RESULTS: 166 men with a mean age of 59 +/- 10 years were
analyzed. The mean preoperative curvature in the entire cohort was 65 degrees
(range = 30-130 degrees ). 94% of patients with MPP had total resolution of their
curvature at the end of the operation, whereas 8 patients (6%) had residual
curvature (25-40 degrees ). In the IPP group 25 of 30 (83.3%) had a straight
penis at the end of surgery, whereas 5 of 30 (16.7%) had residual curvature, with
the mean magnitude being 33 degrees in the MPP group and 30 degrees in the IPP
group. 86% of all patients had diabetes. There were no differences between the 2
implant groups in age, hemoglobin A1c, body mass index, or smoking status. The
mean patient satisfaction was 4.42 +/- 0.70 (range = 2-5) and there was no
difference between the 2 groups. The mean follow-up period was 23.4 months (range
= 6-29 months). CONCLUSION: We found that the MPP is as effective as the IPP in
curvature correction in patients with PD, with similar patient satisfaction for
the 2 groups. Habous M, Farag M, Tealab A, et al. Malleable Penile Implant Is an
Effective Therapeutic Option in Men With Peyronie's Disease and Erectile
Dysfunction. Sex Med 2018;6:24-29.
PMID- 29336943
TI - One time quantitative PCR detection of Pseudomonas aeruginosa to discriminate
intermittent from chronic infection in cystic fibrosis.
AB - BACKGROUND: Chronic airway infection with Pseudomonas aeruginosa is a major risk
factor of progression of lung disease in patients with cystic fibrosis (CF).
Chronic P. aeruginosa infection evolves from intermittent infection that is
amenable to antibiotic eradication, whereas chronically adapted P. aeruginosa
becomes resistant to antibiotic therapy. Discrimination of intermittent versus
chronic infection is therefore of high therapeutic relevance, yet the available
diagnostic methods are only partly satisfactory. The aim of the present study
was, therefore, to evaluate the usage of quantitative PCR (qPCR) to measure
pathogen abundance and to discriminate between intermittent and chronic
Pseudomonas infection in patients with CF. METHOD: Using an established qPCR
protocol, we analyzed the abundance of P. aeruginosa in 141 throats swabs and 238
sputa from CF patients with intermittent or chronic infection with P. aeruginosa,
as determined by standard culture based diagnostics. RESULTS: We observed a large
increase of abundance of P. aeruginosa in throat swabs and sputum samples from
patients with chronic compared to intermittent infections with P. aeruginosa. The
data show that abundance of P. aeruginosa as measured by qPCR is a valuable tool
to discriminate intermittent from chronic infection. Of note, P. aeruginosa
burden seems more sensitive than mucoidity phenotype to discriminate chronic from
intermittent strains. Furthermore we observed that molecular detection in throat
swabs was linked to a viable culture in the sputum when sputum was available.
This result is of special interest in young patients with cystic fibrosis that
often cannot expectorate sputum. We also observed that qPCR in comparison to
culture detected the infection earlier. CONCLUSION: The results suggest that qPCR
detection and quantification of P. aeruginosa is a precious tool to be added to
the diagnostic toolbox in cystic fibrosis.
PMID- 29336944
TI - Editorial commentary: Newborn screening for Fabry disease: Too much too soon?
PMID- 29336945
TI - Current treatment of significant left main coronary artery disease: A review.
AB - Though infrequent, left main stenosis has a major prognostic impact. The
management of left main disease has evolved over the last few decades with the
growing evidence of the efficacy and safety of percutaneous interventions, as
attested by the most recent trials. However, mastery of the technical aspects of
left main bifurcation stenting is essential in ensuring optimal results. This
review focuses on recent data concerning left main angioplasty results as well as
the current technical approaches.
PMID- 29336946
TI - LDL cholesterol: How low to go?
AB - Epidemiology and the results of large-scale outcome trials indicate that the
association of LDL with atherosclerotic cardiovascular disease is causal, and
continuous not only across levels seen in the general population but also down to
sub-physiological values. There is no scientific basis, therefore, to set a
target or 'floor' for LDL cholesterol lowering, and this presents a clinical and
conceptual dilemma for prescribers, patients, and payers. With the advent of
powerful agents such as proprotein convertase/subtilisin kexin type 9 (PCSK9)
inhibitors, LDL cholesterol can be lowered profoundly but health economic
constraints mandate that this therapeutic approach needs to be selective. Based
on the need to maximize the absolute risk reduction when prescribing combination
lipid-lowering therapy, it is appropriate to prioritize patients with the highest
risk (aggressive and established CVD) who will obtain the highest benefit, that
is, those with elevated LDL cholesterol on optimized statin therapy.
PMID- 29336947
TI - Characterization of goose SPMS: Molecular characterization and expression
profiling of SPMS in the goose ovary.
AB - Spermine synthase (SPMS), which converts spermidine into spermine, is essential
for normal cell growth and development processes in humans and other mammals, but
the molecular characterization and expression profiling of the SPMS gene remain
undetermined in goose tissues and ovarian follicles. In this study, the SPMS cDNA
sequence of the Sichuan white goose was cloned and analysed, and SPMS mRNA
expression was profiled in various tissues and ovarian follicles. The results
showed that the open reading frame of the SPMS cDNA sequence was 1092 bp in
length, encoding 363 amino acids with a molecular weight of 41 kDa. Among all the
examined tissues, SPMS expression was highest in the spleen and cerebrum and
lowest in the breast and thigh muscles. SPMS expression in the F1 follicle was
significantly higher than that in the POF (except for POF2) (P < 0.05). Our
results indicate that SPMS might play an important role in follicular development
and ovulation.
PMID- 29336948
TI - The effect of a potentially tamper-resistant oxycodone formulation on opioid use
and harm: main findings of the National Opioid Medications Abuse Deterrence
(NOMAD) study.
AB - BACKGROUND: Escalation of pharmaceutical opioid use and harm in North America is
well-documented, with similar issues emerging in Australia. One response is the
development of tamper-resistant formulations of opioids. A potentially tamper
resistant formulation of controlled-release oxycodone was introduced in Australia
in April, 2014, rapidly replacing the non-tamper-resistant formulation. Our study
is the most systematic and comprehensive examination of the impact of a new
opioid formulation to date, assessing the effect of tamper-resistant formulation
of controlled-release oxycodone on population-level opioid use and opioid-related
harm (ie, overdose, help-seeking, and treatment-seeking); and opioid use,
tampering, and preference for the tamper-resistant formulation of controlled
release oxycodone compared with other drugs or formulations among sentinel
populations likely to tamper with pharmaceutical opioids. METHODS: We conducted
interrupted time-series analyses of opioid sales data and multiple routinely
collected health datasets, followed up a cohort of people who tamper with
pharmaceutical opioids before and after the introduction of the tamper-resistant
formulation of controlled-release oxycodone, and analysed annual surveys of
people who inject drugs. Data were collected from several Australian states: New
South Wales, South Australia, and Tasmania. Meta-analyses (weighted Z tests) were
conducted to synthesise across data sources providing evidence for a given
indicator. FINDINGS: At the population level, we found reduced sales of higher
strengths of controlled-release oxycodone and increased sales of other oxycodone
formulations. No significant effect was observed among population-level
indicators of opioid overdose, or help or treatment-seeking. Mortality data were
not available for inclusion at the time of our study. Meta-analyses across
sentinel populations (ie, prospective cohort, surveys of people who inject drugs,
and clients of supervised injecting facilities or needle and syringe programmes)
indicated reduced controlled-release oxycodone use via tampering (mainly
injection), with no evidence of switching to heroin or other drug use.
INTERPRETATION: This formulation of controlled-release oxycodone reduced
tampering with pharmaceutical opioids among people who inject drugs, but did not
affect population-level opioid use or harm. FUNDING: Mundipharma Australia, the
Australian Government, and the National Health and Medical Research Council.
PMID- 29336949
TI - Evaluating difficult-to-crush opioids in the community.
PMID- 29336950
TI - Daratumumab: Therapeutic asset, biological trap!
AB - OBJECTIVES: Recently, daratumumab has been included in the therapeutic strategies
for myeloma patients. This molecule is an antibody directed against CD38,
strongly expressed on plasma cells. Nevertheless, as CD38 is also present on
erythrocyte membrane, daratumumab interferes with immunohaematological tests,
complicating the selection of compatible blood. METHODS: A total of 14 patients
treated by daratumumab have been followed in our transfusion laboratory. Among
them, 11 have been transfused. Dithiotreitol (DTT) has been used to inhibit the
daratumumab's interference, in the pre-transfusion tests (irregular antibody
screening and cross-match). RESULTS: The red blood cell treatment with DTT has
been very efficacious to inhibit the daratumumab's interference in 13 patients
out of 14. Some precautionary measures had to be taken into account, especially
the pH and the storage conditions. An extended pheno/genotype was an additional
security element in the selection of compatible blood. To simplify and to
optimize the laboratory practices, a decisional flow chart has been written.
CONCLUSION: DTT red blood cell treatment is very useful and efficacious in the
pre-transfusion tests of patients treated with daratumumab. It allows to avoid
the selection of blood bags only on the basis of an extended pheno/genotype, what
is more secure and more ethical with respect to other at higher risk patients. A
clear decisional flow chart allows a quality assurance gait. Collaboration with
physicians is essential.
PMID- 29336952
TI - The Safe Use of Medication by Adolescents Living on Campus.
PMID- 29336951
TI - Design, synthesis and evaluation against Chikungunya virus of novel small
molecule antiviral agents.
AB - Chikungunya virus is a re-emerging arbovirus transmitted to humans by mosquitoes,
responsible for an acute flu-like illness associated with debilitating
arthralgia, which can persist for several months or become chronic. In recent
years, this viral infection has spread worldwide with a previously unknown
virulence. To date, no specific antivirals treatments nor vaccines are available
against this important pathogen. Starting from the structures of two antiviral
hits previously identified in our research group with in silico techniques, this
work describes the design and preparation of 31 novel structural analogues, with
which different pharmacophoric features of the two hits have been explored and
correlated with the inhibition of Chikungunya virus replication in cells.
Structure-activity relationships were elucidated for the original scaffolds, and
different novel antiviral compounds with EC50 values in the low micromolar range
were identified. This work provides the foundation for further investigation of
these promising novel structures as antiviral agents against Chikungunya virus.
PMID- 29336953
TI - Effective use of iron-aluminum rich laterite based soil mixture for treatment of
landfill leachate.
AB - Landfill leachate poses environmental threats worldwide and causes severe issues
on adjacent water bodies and soil by direct discharge. The primary objective of
this study is to analyze the efficient use of compost and laterite mixtures (0,
10, 20, 30 and 40 wt% compost/laterite) on leachate treatment and to investigate
the associated removal efficiencies under different sorption processes.
Therefore, in the experimental design, laterite is used for providing adsorption
characteristics, and compost for activating biological properties of the filter.
The filtering process is continued until major physical changes occur in the
filter at approximately 100 days. The raw leachate used for the experiment shows
higher average values for many analyzed parameters. Parameters for the experiment
are selected based on their availability in raw leachate in the Sri Lanka. During
filtering, removal efficiencies of BOD (>90%), COD (>85%), phosphate (>90%) and
nitrate (75-95%) show higher values for all filters. These removals are mainly
associated with biodegradation, which is activated by the added compost. Perhaps
the removal of nitrate steadily increases with time, which indicates in
denitrification by the added excess carbon from the leachate. The removal of
total suspended solids (TSS) is moderate to high, but conversely, the electric
conductivity (EC) is unsteady, indicating an association between iron exchange
and carbonate degradation. A very high removal efficiency is reported in Fe (90
100%), and wide ranges of efficiencies in Mn (30-90%), Cu (45-85%), Ni (30-93%),
Cd (37-98%), Zn (15-98%), and Pb (35-98%) involve heterogeneous sorption
processes. Furthermore, the normalization of raw leachate by the liquid filtrate
has apparent improvements. The differences (p > .05) in removal efficiencies
between the filters are significant. It can be concluded that the filter with
laterite mixed with 20% of compost has the optimum conditions. Further, the
Fourier-transforminfrared (FT-IR) models for filter media conclude multiple
sorptions and reveal evidence on vacant sites. X-ray diffraction (XRD) analyses
indicate secondary minerals gibbsite, hematite, goethite and kaolinite as the
major minerals that involved on the sorption process.
PMID- 29336954
TI - High voltage fragmentation of composites from secondary raw materials - Potential
and limitations.
AB - The comminution of composites for liberation of valuable components is a costly
and energy-intensive process within the recycling of spent products. It therefore
is continuously studied and optimized. In addition to conventional mechanical
comminution innovative new principles for size reduction have been developed. One
is the use of high voltage (HV) pulses, which is known to be a technology
selectively liberating along phase boundaries. This technology offers the
advantage of targeted liberation, preventing overgrinding of the material and
thus improving the overall processing as well as product quality. In this study,
the high voltage fragmentation of three different non-brittle composites
(galvanized plastics, carbon fibre composites, electrode foils from Li-ion
batteries) was investigated. The influence of pulse rate, number of pulses and
filling level on the liberation and efficiency of comminution is discussed. Using
the guideline VDI 2225 HV, fragmentation is compared to conventional mechanical
comminution with respect to numerous criteria such as cost, throughput, energy
consumption, availability and scalability. It was found that at current state of
development, HV fragmentation cannot compete with mechanical comminution beyond
laboratory scale.
PMID- 29336955
TI - Assessing Gaps in the HIV Care Continuum in Young Men Who Have Sex With Men: The
P18 Cohort Study.
PMID- 29336957
TI - Human-Snake Encounters and Folk Remedies in Nepal.
PMID- 29336956
TI - Reverse transcription loop-mediated isothermal amplification for species-specific
detection of tomato chlorotic spot orthotospovirus.
AB - Tomato chlorotic spot orthotospovirus (TCSV) is an emerging orthotospovirus that
can cause severe disease on tomato plants. There are at least four
orthotospoviruses infecting tomato, and mixed infection of two or more
orthotospoviruses in a single tomato plant is quite common in the field. With
similarity in the symptomatology and cross serological reactivity among tomato
infecting orthotospoviruses, especially between TCSV and groundnut ringspot
orthotospovirus (GRSV), the current serological tests could not achieve definite
and accurate species-specific determination in disease diagnosis. Here, a one
step reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay
was developed for TCSV. Under optimum conditions, the virus was detected in as
little as 0.2 ng of total RNA or in 1:10,000 dilution of a simple diluted tissue
extract, which was ten times more sensitive than a conventional RT-PCR assay. The
RT-LAMP assay was highly specific for TCSV, with no cross reaction with the other
two orthotospoviruses: GRSV and tomato spotted wilt orthotospovirus (TSWV). These
results demonstrate that this simple and sensitive RT-LAMP could be used to
achieve species-specific detection for TCSV under field conditions.
PMID- 29336958
TI - Prehospital Emergencies in Illegal Gold Mining Sites in French Guiana.
AB - INTRODUCTION: Illegal gold mining is flourishing in French Guiana, existing
outside the law due to both the high cost of gold mining permits and the
challenges of law enforcement within the Amazon forest. We report the
characteristics of, and the medical responses to, medical emergencies in illegal
gold mining sites. METHODS: We performed a retrospective study of all medical
emergencies reported from illegal gold mining sites to the centralized call
office of SAMU 973 from 1998 through 2000 and from 2008 through 2010. According
to the national health care system, any medical emergency within the territory is
handled by the prehospital emergency medical service (SAMU 973), irrespective of
the patients' legal status. Data were extracted from the SAMU 973 notebook
registry (1998-2000) or the SAMU 973 computerized database (2008-2010) and werre
collected using a standardized questionnaire. RESULTS: Of 71,932 calls for
medical emergencies in French Guiana during the study periods, 340 (0.5%)
originated from illegal gold mining sites. Of these, 196 (58%) led to medical
evacuation by helicopter, whereas the overall rate of evacuation by helicopter
after placing a call to SAMU 973 was only 4% (3020/71,932; P<0.0001 for
comparison with illegal gold mining sites). Medical emergencies were classified
as illness (48%, mostly infectious), trauma (44%, mostly weapon wounds), and
miscellaneous (8%). CONCLUSIONS: Medical emergencies at illegal gold mining sites
in the Amazon forest mostly include infectious diseases, followed by trauma, and
often require medical evacuation by helicopter. Our study suggests that
implementation of preventive medicine within gold mining sites, irrespective of
their legal status, could be cost-effective and reduce morbidity.
PMID- 29336959
TI - Psychological Attributes of Ultramarathoners.
AB - INTRODUCTION: As the popularity of ultramarathon participation increases, there
still exists a lack of understanding of the unique psychological characteristics
of ultramarathon runners. The current study sought to investigate some of the
psychological and behavioral factors that are involved in ultramarathon running.
METHODS: We obtained information from participants of the Bear Chase Trail Race
via an online survey. This race is a single-day, multidistance race consisting of
a 10 k, half marathon, 50 k, 50 mi, and 100 k run in Lakewood, Colorado, at a
base altitude of 1680 m with total altitude in climbs ranging from 663 to 2591 m.
We correlated information from the Exercise Addiction Inventory and the Patient
Health Questionnaire-2 and demographic information with race finish times.
RESULTS: Out of 200 runners who started the race, 98 (48%) completed the survey.
Over half of the runners were men (61.2%), and the average age was 39.0 years
(SD+/-8.9; range 21-64 years). A number of respondents (20%) screened positive
for exercise addiction concerns. Approximately 20% of our sample screened
positive for depressive symptoms (Patient Health Questionnaire-2 score >3). The
majority of participants reported receiving strong social support from current
partners with regard to their ultramarathon running training time and goals.
CONCLUSIONS: Although only a screening, the number of positive screens on the
Exercise Addiction Inventory suggests use of screening measures with an
ultramarathon running population. Athletes with positive screening tests should
be fully evaluated for depression and exercise addiction because this would
enable appropriate athlete support and treatment referral.
PMID- 29336960
TI - PRO: Prothrombin Complex Concentrate Should Be Used in Preference to Fresh Frozen
Plasma for Hemostasis in Cardiac Surgical Patients.
PMID- 29336961
TI - Chronic Lung Disease and Mortality after Cardiac Surgery: A Prospective Cohort
Study.
AB - OBJECTIVE: To investigate the 1-year survival in cardiac surgical patients with
lung disease, including previously undiagnosed cases. DESIGN: Prospective cohort
study. SETTING: Tertiary hospital. PARTICIPANTS: Patients scheduled for elective
coronary artery bypass graft (CABG) surgery. INTERVENTIONS: None. MEASUREMENTS
AND MAIN RESULTS: Pulmonary function tests (PFTs) were performed in 454 patients
before surgery. Abnormal respiratory patterns were defined as follows:
obstructive (forced expiratory volume in 1 second/forced vital capacity <0.70),
restrictive (forced expiratory volume in 1 second/forced vital capacity >=0.70
and forced vital capacity <80% of predicted), and mixed. Overall 1-year mortality
was 3.3%. Among 31 patients with documented chronic obstructive pulmonary disease
(COPD), mortality was 9.6%, hazard ratio (HR) 1.28, 95% confidence interval (CI)
1.02-12.80, p = 0.04. Of 423 patients without history of COPD, 57 obstructive, 46
restrictive, and 4 mixed abnormal patterns were identified. Of a total of 72 with
obstructive lung disease confirmed by PFT (ie, 15 of COPD patients and 57 newly
identified cases), 6.9% died, HR 2.75, 95% CI 0.98-8.07, p = 0.06. When combined
with cases of COPD where a respiratory abnormality was confirmed (26 patients),
newly diagnosed obstructive lung disease (57 patients) was significantly
associated with 1-year mortality, HR 4.13, 95% CI 1.50-11.42, p = 0.006. The
adjustment for EuroSCORE II did not change the results. CONCLUSIONS: Combination
of confirmed preexisting lung disease and newly diagnosed cases provides a clear
link to mid-term mortality.
PMID- 29336962
TI - Preoperative Left Ventricular Diastolic Dysfunction and One-Year Survival in
Patients Undergoing Transcatheter Aortic Valve Replacement.
PMID- 29336963
TI - Ultrasound Guided Cannulation of the Carotid Artery in Extensive Aortic
Dissection Involving the Aortic Arch Branch Vessels.
PMID- 29336964
TI - Continuous Erector Spinae Plane (ESP) Block for Postoperative Analgesia after
Minimally Invasive Mitral Valve Surgery.
PMID- 29336965
TI - Tracheostomy Insertion During Venovenous Extracorporeal Membrane Oxygenation: Do
the Benefits Outweigh the Risks?
PMID- 29336966
TI - Conversion from Monitored Anesthesia Care to General Anesthesia for Transcatheter
Aortic Valve Replacement.
PMID- 29336967
TI - Con: Activated Clotting Time Should Not Be Monitored During Heparinization for
Vascular Surgery.
PMID- 29336968
TI - Reappearance of Motor-Evoked Potentials During the Rewarming Phase After Deep
Hypothermic Circulatory Arrest.
AB - OBJECTIVE: Although motor-evoked potentials (MEPs) disappear in deep hypothermic
circulatory arrest (DHCA), MEPs have been used to confirm whether motor function
is intact after DHCA. It is crucial to know the timing, body temperature, and MEP
amplitude at MEP reappearance to detect spinal cord ischemia after DHCA. However,
data on these parameters are sparse. The authors investigated the characteristics
of MEPs at reappearance after DHCA. DESIGN: A retrospective observational study.
SETTING: Single national center. PARTICIPANTS: Sixty-one patients who underwent
descending aortic replacement and thoracoabdominal aortic replacement with DHCA
between January 2013 and December 2015. INTERVENTIONS: None. MEASUREMENTS AND
MAIN RESULTS: The authors extracted the following data: time to MEP reappearance
after the end of lower extremity circulatory arrest, bladder temperature (BT) and
nasopharyngeal temperature (NPT) when MEPs recovered, and %amplitude of MEPs
relative to control values at MEP reappearance. The median time to MEP
reappearance was approximately 70 minutes. BT at MEP reappearance ranged from
34.3 degrees C to 34.6 degrees C and NPT ranged from 36.2 degrees C to 36.4
degrees C. At MEP reappearance, %amplitude less than 50% of the control value was
observed in more than 50% of patients. Time to MEP reappearance had a significant
positive association with rewarming time (p < 0.01) and BT (p = 0.03).
CONCLUSIONS: There was a wide variation in MEP amplitude at reappearance during
the rewarming phase. BT was approximately 34 degrees C when MEPs in the leg
recovered. The time to MEP reappearance is influenced significantly by rewarming
time and BT.
PMID- 29336969
TI - Delayed Seroconversion in a Patient With Heparin-Induced Thrombocytopenia.
PMID- 29336970
TI - A Nasal Ventilation Mask for a Morbidly Obese Patient with OSA and Atrial
Fibrillation undergoing Cardioversion.
PMID- 29336971
TI - Inhaled Nitric Oxide (iNO) and Inhaled Epoprostenol (iPGI2) Use in Cardiothoracic
Surgical Patients: Is there Sufficient Evidence for Evidence-Based
Recommendations?
PMID- 29336972
TI - General Anesthesia for Transcatheter Aortic Valve Replacement: Total Intravenous
Anesthesia is Associated with Less Delirium as Compared to Volatile Agent
Technique.
AB - OBJECTIVE: Investigate the effect of volatile anesthesia versus total intravenous
anesthesia on the incidence of postoperative delirium and length of stay in
patients undergoing transcatheter aortic valve replacement under general
anesthesia. DESIGN: Retrospective study. SETTING: Single institution, academic
medical center. PARTICIPANTS: Adult patients who underwent transcatheter aortic
valve replacement under general anesthesia between November 2014 and February
2017. INTERVENTIONS: This study was not an interventional study. MEASUREMENTS AND
MAIN RESULTS: Electronic medical records were reviewed for intraoperative
maintenance anesthetic technique, hospital and intensive care unit length of
stay, 30-day mortality, and documentation of delirium. Delirium was defined as
either 1) positive Confusion Assessment Method for the Intensive Care Unit score
or 2) documentation of delirium or confusion by the care team within 2 days of
surgery. Overall, 116 patients were included and 84 (72%) received a total
intravenous anesthesia technique. Twenty-three patients (20%) had postoperative
delirium. The odds of delirium were lower in patients undergoing transcatheter
aortic valve replacement with total intravenous anesthesia, compared with
volatile anesthesia, even after adjusting for procedure approach (odds ratio
0.22, 95% confidence interval 0.06, 0.79, p = 0.02). No significant difference in
hospital or intensive care unit length of stay was seen after adjusting for
procedural characteristics. CONCLUSIONS: While postoperative delirium is a
complex and multifactorial problem, the type of general anesthetic maintenance
may contribute to the incidence of postoperative delirium in patients undergoing
transcatheter aortic valve replacement, and total intravenous anesthesia may be
an attractive alternative to volatile-based general anesthesia maintenance.
PMID- 29336973
TI - Redo Mitral Surgery: Risk, Outcomes, and the Scope of Transcatheter
Interventions.
PMID- 29336974
TI - Commentary on "Superior Reproducibility of the Leading to Leading Edge and Inner
to Inner Edge Methods in the Ultrasound Assessment of Maximum Abdominal Aortic
Diameter".
PMID- 29336975
TI - Mechanical and Biochemical Role of Fibrin Within a Venous Thrombus.
AB - BACKGROUND: The physical properties of a venous thrombus are derived from
molecular characteristics, including fibrin polymer diameter, density, branching,
and cross-linking. Dense thrombi with thin, highly branched fibrin fibres and
small pores in the meshwork have been observed to be more rigid, less permeable,
and more resistant to lysis. The three dimensional fibrin meshwork acts as the
main structure to entrap and capture erythrocytes, platelets and plasma
components. Attached factors become integrated into the developing thrombus, co
localise with fibrin deposition and act in either a pro- or anticoagulant
capacity. Similarly, factors including blood flow, osmolarity and pH, oxidative
stress, platelet and leukocyte recruitment, and thrombin concentration alter
thrombus composition, architecture, and its mechanical properties. CONCLUSIONS:
Over time, an increase in thrombus cellular composition and a linear decrease in
fibrin content as a function of thrombus age is observed. However, little else is
known regarding the evolution of fibrin based clots. The role of fibrin in
mediating cellular coordination, thrombus maturation, and changes of the venous
wall also requires further research. This review discusses the current impact of
fibrin on thrombus remodeling and addresses the limitations of the work done in
this area.
PMID- 29336976
TI - Venus Flytrap: How an Excitable, Carnivorous Plant Works.
AB - The carnivorous plant Dionaea possesses very sensitive mechanoreceptors. Upon
contact with prey an action potential is triggered which, via an electrical
network - comparable to the nervous system of vertebrates - rapidly closes its
bivalved trap. The 'hunting cycle' comprises a constitutively activated mechanism
for the rapid capture of prey, followed by a well-orchestrated sequence of
activation of genes responsible for tight trap closure, digestion of the prey,
and uptake of nutrients. Decisions on the step-by-step activation are based on
'counting' the number of stimulations of sensory organs. These remarkable animal
like skills in the carnivore are achieved not by taking over genes from its prey
but by modifying and rearranging the functions of genes that are ubiquitous in
plants.
PMID- 29336977
TI - The role of extended venous thromboembolism prophylaxis following urologic pelvic
surgery.
AB - With the emergence of evidence that venous thromboembolisms (VTE) typically
occurs following discharge after urologic pelvic surgery, the focus on extended
VTE prophylaxis has intensified. Urologists should have a comprehensive
understanding of various VTE risk factors in order to weigh the risk of
postoperative hemorrhage with the possibility of fatal pulmonary embolus. Risk
factors such as advanced age, obesity, and active malignancy are especially
common in patient's undergoing urologic pelvic surgery, and thus this issue
becomes particularly relevant to the practicing urologist. In previous years,
guidelines on extended VTE prophylaxis have either been vague or not urology
specific; however, the European Association of Urology has recently issued
recommendations on VTE prophylaxis stratified by VTE risk and surgery type.
Although these guidelines are a major advance, definitive answers on this
question may prove elusive in the form of prospective randomized data given the
low incidence of clinically significant postoperative VTE.
PMID- 29336978
TI - Metastatic burden in newly diagnosed hormone-naive metastatic prostate cancer:
Comparing definitions of CHAARTED and LATITUDE trial.
AB - OBJECTIVES: No uniformity exists in the definition of metastatic burden in
metastatic hormone-naive prostate cancer (mHNPC) across clinical trials making
their comparison challenging. We explored definition agreement and prognostic
significance of bulky mHNPC according to the CHAARTED and LATITUDE trial.
MATERIALS AND METHODS: Since 2014, 95 patients with newly diagnosed mHNPC were
prospectively registered. For this study, they were categorized as having high
volume (HVD) vs. low-volume (LVD) and high-risk (HRD) vs. low-risk disease (LRD)
according to the definition of CHAARTED and LATITUDE, respectively. Agreement was
tested using Cohen's kappa coefficient. The Kaplan-Meier method was used to
compare castration-resistant prostate cancer-free survival (CRPC-FS) and overall
survival (OS). Prognostic significance was analyzed using Cox regression models.
RESULTS: In total, 44 (46%) and 46 (48%) patients showed HVD and HRD,
respectively. Cohen's kappa coefficient was 0.83 indicating "almost perfect"
agreement (P<0.001). Median CRPC-FS was 40 (95% CI: 25-55) vs. 11 months (95% CI:
8-14) for LVD and HVD (P = 0.001); 40 (95% CI: 27-53) vs. 11 months (95% CI: 8
14) for LRD and HRD (P<0.001), respectively. Median OS was not reached vs. 51
months (95% CI: 0-102) for LVD and HVD (P = 0.001); not reached vs. 51 months
(95% CI: 2-100) for LRD and HRD (P = 0.003), respectively. The prognostic
significance of both definitions remained significant in the multivariate model
for CRPC-FS (P = 0.012 and P = 0.003). CONCLUSIONS: There is an excellent
agreement between the definitions of bulky mHNPC in the CHAARTED and LATITUDE
trial. Both definitions have significant prognostic value for predicting worse
CRPC-FS and OS.
PMID- 29336979
TI - Prostate magnetic resonance imaging: The truth lies in the eye of the beholder.
AB - PURPOSE: To determine the diagnostic accuracy and interobserver variability of
radiologic interpretation of magnetic resonance imaging (MRI) performed for
surgical planning before prostatectomy. PATIENTS AND METHODS: The records of 233
men undergoing prostatectomy with presurgical multiparametric 3T surface body
coil MRI were reviewed. All initial films were read by a fellowship-trained body
radiologist provided with relevant clinical information. A senior radiologist
then reread all pelvic MRIs blinded to the initial interpretation with findings
from both readings compared to final pathology. Kappa (kappa) scores as well as
sensitivity, specificity, positive predictive values (PPV), negative predictive
value (NPV), and accuracy were determined. RESULTS: When considering
extraprostatic extension (EPE), there was low concordance comparing the initial
vs. repeat MRI interpretation (kappa = 0.22). Additionally, when the senior
radiologist reread his own initial interpretation (n = 93, blinded to initial
result), concordance for EPE was greater (kappa = 0.36) albeit similarly low.
With regard to EPE, a comparison of initial MRI interpretation vs. reread by
senior radiologist noted universal improvements in diagnostic characteristics
including sensitivity (30.3% vs. 56.1%), specificity (80.2% vs. 88.6%), PPV
(37.7% vs. 66.1%), NPV (74.4% vs. 83.6%), and accuracy (66.1% vs. 79.4%). In
contrast, seminal vesicle invasion interpretation was more uniform whereby
initial MRI interpretation vs. reread yielded similar sensitivity (18.2% vs.
27.3%), specificity (97.2% vs. 93.8%), PPV (40.0% vs. 31.6%), NPV (91.9% vs.
92.5%), and accuracy (89.7% vs. 87.6%). CONCLUSIONS: Even at a tertiary referral
center, interobserver variability among radiologists regarding local extent of
disease on prostate MRI is high. These observations underscore the importance of
uniformity when defining criteria for EPE and seminal vesicle invasion to allow
for optimal presurgical planning.
PMID- 29336980
TI - Surfactant Effects on Lipid-Based Vesicles Properties.
AB - Understanding the effect of surfactant properties is critical when designing
vesicular delivery systems. This review evaluates previous studies to explain the
influence of surfactant properties on the behavior of lipid vesicular systems,
specifically their size, charge, stability, entrapment efficiency,
pharmacokinetics, and pharmacodynamics. Generally, the size of vesicles decreases
by increasing the surfactant concentration, carbon chain length, the
hydrophilicity of the surfactant head group, and the hydrophilic-lipophilic
balance. Increasing surfactant concentration can also lead to an increase in
charge, which in turn reduces vesicle aggregation and enhances the stability of
the system. The vesicles' entrapment efficiency not only depends on the
surfactant properties but also on the encapsulated drug. For example, the
encapsulation of a lipophilic drug could be enhanced by using a surfactant with a
low hydrophilic-lipophilic balance value. Moreover, the membrane permeability of
vesicles depends on the surfactant's carbon chain length and transition
temperature. In addition, surfactants have a clear influence on pharmacokinetics
and pharmacodynamics such as sustaining drug release, enhancing the circulation
time of vesicles, improving targeting and cellular uptake.
PMID- 29336982
TI - IL-6 receptor blockade ameliorates diabetic nephropathy via inhibiting
inflammasome in mice.
AB - BACKGROUND AND OBJECTIVE: Interleukin 6 (IL-6) has been identified as a key
mediator in inflammation, immune responses and glucose metabolism. In this study,
we assessed the effects of an IL-6 receptor antibody on diabetic nephropathy in a
mouse model of type 2 diabetes mellitus. METHODS: Twelve week old male db/db mice
were treated with Tocilizumab (an IL-6 receptor antibody), normal IgG1 control
antibody, insulin or normal saline for 12 weeks. Renal injury, inflammation and
insulin resistance were assessed. RESULTS: Db/db mice treated with Tocilizumab
exhibited reduced proteinuria and glomerular mesangial matrix accumulation
compared to db/db + IgG controls. Additionally, Tocilizumab suppressed
inflammatory response, oxidative stress and the IL-6 signaling pathway in the
diabetic kidneys. It is noteworthy that blockade of IL-6 receptor blunted the
activation of NLRP3 inflammasome partly through inhibition of IL-17A.
Furthermore, insulin resistance assessed by glucose tolerance test, was
ameliorated by Tocilizumab treatment. CONCLUSIONS: The protective effects of an
IL-6 receptor blockade against diabetic renal injury may be due to decreased
insulin resistance and inhibition of the inflammasome.
PMID- 29336981
TI - Challenges and Opportunities for the Subcutaneous Delivery of Therapeutic
Proteins.
AB - Biotherapeutics is a rapidly growing drug class, and over 200 biotherapeutics
have already obtained approval, with about 50 of these being approved in 2015 and
2016 alone. Several hundred protein therapeutic products are still in the
pipeline, including interesting new approaches to treatment. Owing to patients'
convenience of at home administration and reduced number of hospital visits as
well as the reduction in treatment costs, subcutaneous (SC) administration of
biologics is of increasing interest. Although several avenues for treatment using
biotherapeutics are being explored, there is still a sufficient gap in knowledge
regarding the interplay of formulation conditions, immunogenicity, and
pharmacokinetics (PK) of the absorption of these compounds when they are given
SC. This review seeks to highlight the major concerns and important factors
governing this route of administration and suggest a holistic approach for
effective SC delivery.
PMID- 29336983
TI - A response to S. Basu (2017).
PMID- 29336984
TI - Can the problem of the observability of other minds be solved in the lab?:
Comment on "Seeing mental states: An experimental strategy for measuring the
observability of other minds" by Cristina Becchio et al.
PMID- 29336986
TI - A systematic literature review of observational studies of the bidirectional
association between metabolic syndrome and migraine.
AB - AIMS: To evaluate all epidemiological evidence in the literature linking the
metabolic syndrome (MetS) and migraine in adults. METHODS: Database (Medline,
Embase; published reports up to November 2017) and manual searches were
performed. Information on data collection, sample characteristics, study design,
MetS and migraine assessment, and results was extracted from each relevant
publication. The methodological quality of each study was also assessed. RESULTS:
A total of 15 observational epidemiological studies in adults, published between
2009 and 2017, were retrieved. Of these, one employed a prospective design, while
the rest had a cross-sectional (13 studies) or case-control (one study) design.
Five studies assessed the presence of migraine in individuals with MetS, whereas
10 studies assessed the presence or risk of MetS in migraineurs. Most
participants were female hospital outpatients. The sole prospective cohort study
reported 11-year MetS incidence of 21.8% in migraineurs with aura, 16.8% in
migraineurs without aura and 14.5% in subjects without headaches. Most studies
(60%) provided no statistical estimates of association. Methodological flaws
included selection biases, lack of power analysis, unsuitable research plans and
no multivariable analyses. Meta-analysis was not feasible with the available
data. CONCLUSION: Our systematic review has identified major gaps in knowledge
and weaknesses in research that should provide an impetus for future
epidemiological investigations using more rigorous methodology, large general
population prospective cohorts, and substantial data on dietary behaviours and
lifestyle.
PMID- 29336985
TI - The Blacklegged Tick, Ixodes scapularis: An Increasing Public Health Concern.
AB - In the United States, the blacklegged tick, Ixodes scapularis, is a vector of
seven human pathogens, including those causing Lyme disease, anaplasmosis,
babesiosis, Borrelia miyamotoi disease, Powassan virus disease, and ehrlichiosis
associated with Ehrlichia muris eauclarensis. In addition to an accelerated rate
of discovery of I. scapularis-borne pathogens over the past two decades, the
geographic range of the tick, and incidence and range of I. scapularis-borne
disease cases, have increased. Despite knowledge of when and where humans are
most at risk of exposure to infected ticks, control of I. scapularis-borne
diseases remains a challenge. Human vaccines are not available, and we lack solid
evidence for other prevention and control methods to reduce human disease. The
way forward is discussed.
PMID- 29336988
TI - Superior Mesenteric Artery Syndrome: An Uncommon Cause of Abdominal Pain.
PMID- 29336987
TI - The in vitro radiosensitizer potential of resveratrol on MCF-7 breast cancer
cells.
AB - Radiation therapy is commonly applied in breast cancer (BC) patients. However,
radioresistance and side effects are limiting factors of this practice.
Therefore, studying substances that can enhance the radiation effect and, at the
same time, protect normal cells is very relevant. Thus, the aim of this work was
to assess the radiosensitizer effect of resveratrol (RV) on BC cells (MCF-7). A
high cytotoxic and antiproliferative effect was observed in the treatment with 10
MUM of RV + 3 Gy ionizing radiation (IR). Our results indicate that, 24 h after
the exposition of cell cultures to RV + IR, an induction of necrosis/senescence
has occurred. Furthermore, was observed the activation of extrinsic apoptosis
pathway through a decrease of the Bax/Bcl-2 ratio and a high activity of caspase
8. Moreover, our data show that this treatment affected the oxidative cell
metabolism, increasing oxidative protein, lipid and membrane damage and also
acted to decrease the antioxidant enzymes activity. The antiproliferative effect
on 72 h cultures may be associated with a high expression of p53 and an
interruption of cell cycle in the S phase. Therefore, our results suggest that RV
is a potential radiosensitizer of MCF-7 BC cells.
PMID- 29336989
TI - Are Geriatric Patients Placed in an Emergency Department Observation Unit on a
Chest Pain Pathway More Likely Than Non-Geriatric Patients to Re-Present to the
Hospital within 30 Days?
AB - BACKGROUND: Emergency department observation units (EDOUs) are used frequently
for low-risk chest pain evaluations. OBJECTIVE: The purpose of this study was to
determine whether geriatric compared to non-geriatric patients evaluated in an
EDOU for chest pain have differences in unscheduled 30-day re-presentation,
length of stay (LOS), and use of stress testing. METHODS: We conducted an
exploratory, retrospective, cohort study at a single academic, urban ED of all
adult patients placed in an EDOU chest pain protocol from June 1, 2014 to May 31,
2015. Our primary outcome was any unscheduled return visits within 30 days of
discharge from the EDOU. Secondary outcomes included EDOU LOS and stress testing.
We used Wilcoxon non-parametric and chi2 tests to compare geriatric to non
geriatric patients. RESULTS: There were 959 unique EDOU placements of geriatric
(n = 219) and non-geriatric (n = 740) patients. Geriatric compared to non
geriatric patients had: no significant difference in unscheduled 30-day return
visits after discharge from the EDOU (15.5% vs. 18.5%; p = 0.31); significantly
longer median EDOU LOS (22.1 vs. 20.6 h; p < 0.01) with a greater percentage
staying longer than 24 h (42% vs. 29.1%; p < 0.01). Geriatric patients had
significantly fewer stress tests (39.7% vs. 51.4%; p < 0.01), more of which were
nuclear stress tests (78.2% vs. 39.5%; p < 0.01). CONCLUSIONS: In this
exploratory retrospective study, geriatric EDOU chest pain patients did not have
an increased rate of re-presentation to the hospital within 30 days compared to
non-geriatric patients. Geriatric patients had a longer EDOU LOS than non
geriatric patients. Geriatric patients in the EDOU had fewer stress tests, but
more of those were nuclear stress tests.
PMID- 29336990
TI - Failure of Intracardiac Pacing After Fatal Propafenone Overdose: A Case Report.
AB - BACKGROUND: Propafenone is a sodium-channel blocker, class IC antiarrhythmic
drug, frequently used to manage supraventricular dysrhythmias, especially atrial
fibrillation. We report a self mono-intoxication with propafenone. CASE REPORT: A
68-year-old woman presented with a decreased level of consciousness, hypotension,
and electrocardiogram showing QRS widening with atrial asystole and extreme
bradycardia < 20 beats/min. After initial stabilization with transcutaneous
pacing, laboratory findings detected normal electrolyte ranges and metabolic
acidosis, and her medical history revealed availability of propafenone due to
paroxysmal atrial fibrillation and depressive syndrome, which led to the
suspicion of intoxication. Despite intravenous sodium bicarbonate, calcium,
norepinephrine, and aggressive fluid replacement (10% glucose with insulin),
hemodynamic stability was not achieved. Temporary intracardiac pacing was
implanted. However, even with multiple electrode positions, effective capture
could not be achieved. At that time, transcutaneous pacing was also ineffective.
Consequently, the patient died in refractory asystole due to complete myocardial
nonexcitability. The concentration of 5270 ng/mL of propafenone was found in the
blood at autopsy, using gas spectrometry-mass chromatography. It is the third
highest reported propafenone lethal concentration and the first case in which the
myocardial nonexcitability refractory to intracardiac pacing was seen despite
normal electrode position in the right ventricle, with failure to achieve the
patient's hemodynamic stability. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF
THIS?: Emergency physicians should be aware of possible propafenone ingestion
causing toxicity, which is probably more frequent than previously described,
especially because propafenone is widely available due to its use in managing
atrial fibrillation, the most common arrhythmia nowadays.
PMID- 29336991
TI - SIRPalpha-CD47 Immune Checkpoint Blockade in Anticancer Therapy.
AB - Inhibitory immune checkpoint blockade has been one of the most significant
advances in anticancer therapy of the past decade. Research so far has largely
focused on improving adaptive immune functions, but recent studies have indicated
that the signal-regulatory protein (SIRP)alpha-CD47 pathway, a phagocytosis
checkpoint in macrophages and other innate immune cells, may be an interesting
therapeutic target. Here, we summarize current knowledge about SIRPalpha-CD47
blockade, and highlight key issues for future investigations. These include the
targeting of prophagocytic receptors (Fc receptors or otherwise) to complement
SIRPalpha-CD47 blockade, the understanding of constraints on phagocytosis other
than the SIRPalpha-CD47 checkpoint and the contribution of immune cells other
than macrophages. A better understanding of how SIRPalpha-CD47 blockade works may
aid in identifying patients suitable for this therapy, avoiding potential
toxicities and designing optimal combination therapies.
PMID- 29336992
TI - Schwann cell lamellipodia regulate cell-cell interactions and phagocytosis.
AB - Lamellipodia in Schwann cells (SCs) are crucial for myelination, but their other
biological functions remain largely uncharacterised. Two types of lamellipodia
exist in SCs: axial lamellipodia at the outermost edge of the cell processes, and
radial lamellipodia appearing peripherally along the entire cell. We have
previously shown that radial lamellipodia on olfactory glia (olfactory
ensheathing cells; OECs) promote cell-cell adhesion, contact-mediated migration
and phagocytosis. Here we have investigated whether lamellipodia in SCs have
similar roles. Using live-cell imaging, we show that the radial lamellipodia in
SCs are highly motile, appear at multiple cellular sites and rapidly move in a
wave-like manner. We found that axial and radial lamellipodia had strikingly
different roles and are regulated by different intracellular pathways. Axial
lamellipodia initiated interactions with other SCs and with neurons by contacting
radial lamellipodia on SCs, and budding neurites/axons. Most SC-SC interactions
resulted in repulsion, and, lamellipodial activity (unlike in OECs) did not
promote contact-mediated migration. We show that lamellipodia are crucial for SC
mediated phagocytosis of both axonal debris and bacteria, and demonstrated that
inhibition of lamellipodial activity by blocking the Rho/Rac pathways also
inhibits phagocytosis. We also show that heregulin, which induces SC
differentiation and maturation, alters lamellipodial behaviour but does not
affect phagocytic activity. Overall, the results show that SC lamellipodia are
important for cell interactions and phagocytosis.
PMID- 29336993
TI - WORLDSymposiumTM 2018 Introduction.
PMID- 29336994
TI - Agreement between the results of meta-analyses from case reports and from
clinical studies regarding the efficacy of laronidase therapy in patients with
mucopolysaccharidosis type I who initiated enzyme replacement therapy in adult
age: An example of case reports meta-analyses as an useful tool for evidence
based medicine in rare diseases.
AB - BACKGROUND: Case reports might have a prominent role in the rare diseases field,
due to the small number of patients affected by one such disease. A previous
systematic review regarding the efficacy of laronidase therapy in patients with
mucopolysaccharidosis type I (MPS-I) who initiated enzyme replacement therapy
(ERT) in adult age has been published. The review included a meta-analysis of 19
clinical studies and the description of eleven case reports. It was of interest
to perform a meta-analysis of those case reports to explore the role of such meta
analyses as a tool for evidence-based medicine in rare diseases. METHODS: The
study included all case reports with standard treatment regimen. Primary analysis
was the percentage of case reports showing an improvement in a specific outcome.
Only when that percentage was statistically higher than 5%, the improvement was
confirmed as such. The outcomes that accomplished this criterion were ranked and
compared to the GRADE criteria obtained by those same outcomes in the previous
meta-analysis of clinical studies. RESULTS: There were three outcomes that had a
significant improvement: Urine glycosaminoglycans, liver volume and 6-minute
walking test. Positive and negative predictive values, sensitivity and
specificity for the results of the meta-analysis of case reports as compared to
that of clinical studies were 100%, 88.9%, 75% and 100%, respectively.
Accordingly, absolute (Rho=0.82, 95%CI: 0.47 to 0.95) and relative agreement
(Kappa=0.79, 95%CI: 0.593 to 0.99) between the number of case reports with
improvement in a specific outcome and the GRADE evidence score for that outcome
were good. Sensitivity analysis showed that agreement between the meta-analysis
of case reports and that of the clinical studies were good only when using a
strong confirmatory strategy for outcome improvement in case reports.
CONCLUSIONS: We found an agreement between the results of meta-analyses from case
reports and from clinical studies in the efficacy of laronidase therapy in
patients with MPS-I who initiated ERT in adult age. This agreement suggests that
combining case reports quantitatively, rather than analyzing them separately or
qualitatively, may improve conclusions in the field of rare diseases.
PMID- 29336995
TI - A search for molecular mechanisms underlying male idiopathic infertility.
AB - Infertility affects approximately 15% of the couples wanting to conceive. In 30 -
40% of the cases the aetiology of male infertility remains unknown and is called
idiopathic male infertility. When assisted reproductive technologies are used to
obtain pregnancy, an adequate (epi)genetic diagnosis of male infertility is of
major importance to evaluate if a genetic abnormality will be transmitted to the
offspring. In addition, there is need for better diagnostic seminal biomarkers to
assess the success rates of these assisted reproductive technologies. This review
investigated the possible causes and molecular mechanisms underlying male
idiopathic infertility by extensive literature searches of: (i) causal gene
mutations; (ii) proteome studies of spermatozoa from idiopathic infertile
men;(iii) the role of epigenetics; (iv) post-translational modifications; and (v)
sperm DNA fragmentation in infertile men. In conclusion, male infertility is a
complex, multi-factorial disorder and the underlying causes often remain unknown.
Further research on the (epi)genetic and molecular defects in spermatogenesis and
sperm function is necessary to improve the diagnosis and to develop more
personalized treatments of men with idiopathic infertility.
PMID- 29336996
TI - Follicular flushing in patients with poor ovarian response: a systematic review
and meta-analysis.
AB - A systematic literature review and meta-analysis was conducted to evaluate the
effect of follicular flushing on clinical outcomes (primary outcome: mean number
of cumulus-oocyte-complexes [COC]) in poor-response IVF patients). The
bibliographic databases OvidMedline (includes Pubmed), Cochrane Library and Web
of Science were searched electronically for randomized controlled trials (RCT)
comparing follicular flushing with no flushing. Three RCT with a total of 210
patients could be included. The mean number of COC did not increase with flushing
(weighted mean difference: -0.45 COC, 95% CI -1.14 to 0.25, I2 = 70%; P = 0.21;
three RCT, n = 210). Mean number of metaphase II oocytes and the proportion of
randomized patients having at least one COC retrieved were no different between
groups. No difference was observed between groups for mean number of embryos, the
proportion of randomized patients achieving embryo transfer, clinical pregnancy
and live birth rates. Procedure duration was significantly increased with
flushing (P = 0.0006). A positive effect of flushing on any of the investigated
outcomes could not be observed in the existing literature in patients with poor
ovarian response. Flushing is unlikely to significantly increase the number of
oocytes, and the routine use of follicular flushing should, therefore, be
scrutinized.
PMID- 29336997
TI - Modulation of nonessential amino acid biosynthetic pathways in virulent Hessian
fly larvae (Mayetiola destructor), feeding on susceptible host wheat (Triticum
aestivum).
AB - Compatible interactions between wheat (Triticum aestivum), and its dipteran pest
Hessian fly (Hf, Mayetiola destructor) result in successful establishment of
larval feeding sites rendering the host plant susceptible. Virulent larvae employ
an effector-based feeding strategy to reprogram the host physiology resulting in
formation of a protein- and sugar-rich nutritive tissue beneficial to developing
larvae. Previous studies documented increased levels of nonessential amino acids
(NAA; that need not be received through insect diet) in the susceptible wheat in
response to larval feeding, suggesting importance of plant-derived NAA in larval
nutrition. Here, we investigated the modulation of genes from NAA biosynthetic
pathways (NAABP) in virulent Hf larvae. Transcript profiling for 16 NAABP genes,
annotated from the recently assembled Hf genome, was carried out in the feeding
first-, and second-instars and compared with that of the first-instar neonate
(newly hatched, migrating, assumed to be non-feeding) larvae. While Tyr, Gln,
Glu, and Pro NAABP genes transcript abundance declined in the feeding instars as
compared to the neonates, those for Ala, and Ser increased in the feeding larval
instars, despite higher levels of these NAA in the susceptible host plant. Asp,
Asn, Gly and Cys NAABP genes exhibited variable expression profiles in the
feeding first- and second-instars. Our results indicate that while Hf larvae
utilize the plant-derived NAA, de novo synthesis of several NAA may be necessary
to: (i) provide larvae with the requisite amount for sustaining growth before
nutritive tissue formation and, (ii) overcome any inadequate amounts in the host
plant, post-nutritive tissue formation.
PMID- 29336998
TI - Developing a Predictive Model for Clinical Outcomes of Advanced Non-Small Cell
Lung Cancer Patients Treated With Nivolumab.
AB - INTRODUCTION: Despite significant improvement of clinical outcomes of advanced
non-small-cell lung cancer (NSCLC) patients treated with immunotherapy, our
knowledge of optimal biomarkers is still limited. PATIENTS AND METHODS: We
retrospectively evaluated 159 advanced NSCLC patients in our institution treated
with nivolumab after disease progression during platinum-based chemotherapy. We
correlated several variables with progression-free survival (PFS) to develop the
immunotherapy, Sex, Eastern Cooperative Oncology Group performance status,
Neutrophil-to-lymphocyte ratio (NLR), and Delta NLR (iSEND) model. We categorized
patients into iSEND good, intermediate, and poor risk groups and evaluated their
clinical outcomes. Performance of iSEND at 3, 6, 9, and 12 months was evaluated
according to receiver operating characteristic (ROC) curves and internally
validated using bootstrapping. The association of iSEND risk groups with clinical
benefit was evaluated using logistic regression. RESULTS: Median follow-up was
11.5 months (95% confidence interval [CI], 9.4-13.1). There were 50 deaths and 43
with disease progression without death. PFS rates at 3, 6, 9, and 12 months were
78.4%, 63.7%, 55.3%, and 52.2% in iSEND good; 79.4%, 44.3%, 25.9%, and 19.2% in
iSEND intermediate; and 65%, 25.9%, 22.8%, and 17.8% in iSEND poor. Time
dependent area under ROC curves of iSEND for PFS at 3, 6, 9, and 12 months were
0.718, 0.74, 0.746, and 0.774. The iSEND poor group was significantly associated
with progressive disease at 12 +/- 2 weeks (odds ratio, 9.59; 95% CI, 3.8-26.9; P
< .0001). CONCLUSION: The iSEND model is an algorithmic model that can
characterize clinical outcomes of advanced NSCLC patients receiving nivolumab
into good, intermediate, or poor risk groups and might be useful as a predictive
model if validated independently.
PMID- 29336999
TI - Faculty Relative Value Unit Incentives and Resident Education.
PMID- 29337000
TI - Mechanical Forces Program the Orientation of Cell Division during Airway Tube
Morphogenesis.
AB - Oriented cell division plays a key role in controlling organogenesis. The
mechanisms for regulating division orientation at the whole-organ level are only
starting to become understood. By combining 3D time-lapse imaging, mouse
genetics, and mathematical modeling, we find that global orientation of cell
division is the result of a combination of two types of spindles with distinct
spindle dynamic behaviors in the developing airway epithelium. Fixed spindles
follow the classic long-axis rule and establish their division orientation before
metaphase. In contrast, rotating spindles do not strictly follow the long-axis
rule and determine their division orientation during metaphase. By using both a
cell-based mechanical model and stretching-lung-explant experiments, we showed
that mechanical force can function as a regulatory signal in maintaining the
stable ratio between fixed spindles and rotating spindles. Our findings
demonstrate that mechanical forces, cell geometry, and oriented cell division
function together in a highly coordinated manner to ensure normal airway tube
morphogenesis.
PMID- 29337001
TI - Antidepressant Treatment Duration in Pediatric Depressive and Anxiety Disorders:
How Long is Long Enough?
AB - Anxiety and depressive disorders are common in the pediatric primary care
setting, and respond to both psychotherapeutic and psychopharmacologic treatment.
However, there are limited data regarding the optimal treatment duration. This
article systematically reviews guidelines and clinical trial data related to
antidepressant treatment duration in pediatric patients with depressive and
anxiety disorders. The extant literature suggests 9-12 months of antidepressant
treatment for youth with major depressive disorder. For generalized, separation
and social anxiety disorders, 6-9 months of antidepressant treatment may be
sufficient, though many clinicians extend treatment to 12 months based on
extrapolation of data from adults with anxiety disorders. Such extended treatment
periods may decrease the risk of long-term morbidity and recurrence; however, the
goal of treatment is ultimately remission, rather than duration of antidepressant
pharmacotherapy. Moreover, while evidence-based guidelines represent a starting
point, appropriate treatment duration varies and patient-specific response,
psychological factors, and timing of discontinuation must be considered for
individual pediatric patients.
PMID- 29337002
TI - Hypothalamic inflammation and malfunctioning glia in the pathophysiology of
obesity and diabetes: Translational significance.
AB - Preclinical studies have suggested that chronic inflammation in the brain might
be associated with multiple metabolic disorders, including obesity and diabetes.
In particular, hypothalamic inflammation interferes with the endocrine system and
modulates nutritional homeostasis, leading to metabolic alterations and
consequent pathologies. With regard to the mechanisms underlying molecular and
cellular pathogenesis, neurons, non-neuronal cells, and the crosstalk between
them have gained particular attention. Specifically, malfunctioning glia have
recently been implicated as an important component of pathological hypothalamic
inflammation. Hypothalamic inflammation modulates food intake, energy
expenditure, insulin secretion, hepatic glucose production, and glucose and fatty
acid metabolism. Moreover, growing evidence suggests that hypothalamic
inflammation is intrinsically associated with the pathogenesis of obesity,
diabetes, and their dysfunctional consequences. However, the translational
significance of hypothalamic inflammation has not yet been fully explored. In
this review, we cover recent advances suggesting that hypothalamic inflammation
and glia play a central role in the ontology of obesity, diabetes, and their
complications. Finally, we explore the possibilities and challenges of targeting
hypothalamic inflammation as a potential therapeutic strategy.
PMID- 29337003
TI - Mouse lung fibroblasts are highly susceptible to necroptosis in a reactive oxygen
species-dependent manner.
AB - Mouse embryonic fibroblasts (MEFs) have extensively been used to study
necroptosis, a recently identified form of programmed cell death. However, very
little is yet known about the role of necroptosis and its regulation by reactive
oxygen species (ROS) in cell types naturally exposed to high oxygen levels such
as mouse lung fibroblasts (MLFs). Here, we discover that MLFs are highly
susceptible to undergo necroptosis in a ROS-dependent manner upon exposure to a
prototypic death receptor-mediated necroptotic stimulus, i.e. cotreatment with
tumor necrosis factor (TNF)alpha, Smac mimetic and the caspase inhibitor zVAD.fmk
(TSZ). Kinetic analysis revealed that TSZ rapidly induces cell death in MLFs.
Pharmacological inhibition of receptor-interacting protein kinase (RIPK)1 by
necrostatin-1 (Nec-1) or RIPK3 by GSK'872 significantly rescues TSZ-stimulated
cell death. Also, genetic silencing of RIPK3 or mixed lineage kinase domain-like
pseudokinase (MLKL) significantly protects MLFs from TSZ-mediated cell death.
Prior to cell death, TSZ significantly increases production of ROS. Importantly,
addition of radical scavengers such as butylated hydroxyanisole (BHA) or alpha
Tocopherol (alpha-Toc) significantly suppresses TSZ-induced cell death in
parallel with a significant reduction of ROS generation. Consistently, BHA
prevented TSZ-triggered phosphorylation of MLKL similar to the addition of
GSK'872. Thus, our study demonstrates for the first time that MLFs are prone to
undergo necroptosis in response to a prototypic necroptotic stimulus and
identifies ROS as important mediators of TSZ-triggered necroptosis.
PMID- 29337004
TI - Quantitative sensory testing profiles in children, adolescents and young adults
(6-20 years) with cerebral palsy: Hints for a neuropathic genesis of pain
syndromes.
AB - INTRODUCTION: Many patients with cerebral palsy (CP) suffer chronic pain as one
of the most limiting factors in their quality of life. In CP patients, pain
mechanisms are not well understood, and pain therapy remains a challenge.
Quantitative sensory testing (QST) might provide unique information about the
functional status of the somatosensory system and therefore better guide pain
treatment. OBJECTIVES: To understand better the underlying pain mechanisms in
pediatric CP patients, we aimed to assess clinical and pain parameters, as well
as QST profiles, which were matched to the patients' cerebral imaging pathology.
PATIENTS AND METHODS: Thirty CP patients aged 6-20 years old (mean age 12 years)
without intellectual impairment underwent standardized assessments of QST.
Cerebral imaging was reassessed. QST results were compared to age- and sex
matched controls (multiple linear regression; Fisher's exact test; linear
correlation analysis). RESULTS: CP patients were less sensitive to all mechanical
and thermal stimuli than healthy controls but more sensitive to all mechanical
pain stimuli (each p < 0.001). Fifty percent of CP patients showed a combination
of mechanical hypoesthesia, thermal hypoesthesia and mechanical hyperalgesia; 67%
of CP patients had periventricular leukomalacia (PVL), which was correlated with
mechanic (r = 0.661; p < 0.001) and thermal (r = 0.624; p = 0.001) hypoesthesia.
CONCLUSION: The combination of mechanical hypoesthesia, thermal hypoesthesia and
mechanical hyperalgesia in our CP patients implicates lemniscal and
extralemniscal neuron dysfunction in the thalamus region, likely due to PVL. We
suspect that extralemniscal tracts are involved in the original of pain in our CP
patients, as in adults.
PMID- 29337005
TI - Walker-Warburg syndrome and tectocerebellar dysraphia: A novel association caused
by a homozygous DAG1 mutation.
AB - OBJECTIVES: To elaborate the imaging phenotype associated with a homozygous
c.743C > del frameshift mutation in DAG1 leading to complete absence of both
alpha- and beta-dystroglycan previously reported in a consanguineous Israeli-Arab
family. METHODS: We analyzed prenatal and postnatal imaging data of patients from
a consanguineous Israeli-Arab kindred harboring the DAG1 mutation. RESULTS: The
imaging studies (fetal ultrasound, CT scan and postnatal MRI) demonstrated: flat
cortex (abnormally thick with irregular pebbled cortical-white matter border on
MRI), hydrocephalus, scattered small periventricular heterotopia and subependymal
hemorrhages and calcifications, z-shaped brainstem, and in addition an occipital
encephalocele, vermian agenesis, and an elongated and thick tectum
(tectocerebellar dysraphia). CONCLUSIONS: The novel association of cobblestone
malformation with tectocerebellar dysraphia as part of WWS is characteristic of
the homozygous c.743C > del frameshift mutation in the DAG1 gene.
PMID- 29337007
TI - Postnatal post-traumatic stress: An integrative review.
AB - PROBLEM: Post-traumatic stress disorder and post-traumatic stress symptoms
following birth occur amongst a small proportion of women but can lead to poor
maternal mental health, impairment in mother-infant bonding and relationship
stress. This integrative review aims to examine the associated risk factors and
women's own experiences of postnatal post-traumatic stress in order to better
understand this phenomenon. METHOD: Fifty three articles were included and
critically reviewed using the relevant Critical Appraisal Skills Program
checklists or Strengthening the Reporting of Observational studies in
Epidemiology assessment tool. FINDINGS: Risk factors for postnatal post-traumatic
stress symptoms and disorder include factors arising before pregnancy, during the
antenatal period, in labour and birth and in the postnatal period. Potential
protective factors against postnatal post-traumatic stress have been identified
in a few studies. The development of postnatal post-traumatic stress can lead to
negative outcomes for women, infants and families. DISCUSSION: Risk factors for
post-traumatic stress symptoms and disorder are potentially identifiable pre
pregnancy and during the antenatal, intrapartum and postnatal periods. Potential
protective factors have been identified however they are presently under
researched. Predictive models for postnatal post-traumatic stress disorder
development have been proposed, however further investigation is required to test
such models in a variety of settings. CONCLUSIONS: Postnatal post-traumatic
stress symptoms and disorder have been shown to negatively impact the lives of
childbearing women. Further investigation into methods and models for identifying
women at risk of developing postnatal post-traumatic stress following childbirth
is required in order to improve outcomes for this population of women.
PMID- 29337006
TI - Relation Between Dietary Essential Fatty Acid Intake and Dry Eye Disease and
Meibomian Gland Dysfunction in Postmenopausal Women.
AB - PURPOSE: To evaluate the relationship between omega-3 (n-3) and omega-6 (n-6)
fatty acids with dry eye disease (DED) and meibomian gland dysfunction (MGD).
DESIGN: Cross-sectional study. METHODS: Postmenopausal women (n = 439) underwent
a clinical evaluation and completed the Vio Food Frequency Questionnaire to
estimate their dietary intake of n-3s and n-6s. Subjects were categorized into 2
binary classifications based on whether or not they had (1) DED and (2) MGD. Mean
intake of dietary fatty acids was compared with 2-sample t tests. Univariate
logistic regression models were used to estimate the odds ratios for each
condition associated with each quintile of n-3s, n-6s, and n-6:n-3 ratios.
RESULTS: For DED vs non-DED, there were no significant differences in n-3 intake
(1.95 +/- 1.47 g vs 1.92 +/- 1.24 g, P = .86), n-6 intake (15.58 +/- 11.56 g vs
15.44 +/- 10.61 g, P = .91), and n-6:n-3 (8.30 +/- 2.57 vs 8.30 +/- 2.57, P =
.99). For MGD vs non-MGD, there were no significant differences in n-3 intake
(1.87 +/- 1.35 vs 1.96 +/- 1.39, P = .61), n-6 intake (15.26 +/- 11.85 vs 15.62
+/- 10.93, P = .80), and n-6:n-3 (8.35 +/- 2.94 vs 8.28 +/- 2.42, P = .84). The
odds ratios (OR) for DED did not differ significantly from 1.0 for n-3, n-6, or n
6:n-3. High n-3 consumption (OR = 0.22 [0.06-0.78]) and moderate n-6 consumption
(OR = 0.37 [0.15-0.91]) were associated with a decreased frequency of MGD.
CONCLUSIONS: Dietary consumption of n-3s and n-6s showed no association with DED,
but high n-3 consumption and moderate n-6 consumption were protective against MGD
in this large sample of postmenopausal women.
PMID- 29337008
TI - Ice pack induced perineal analgesia after spontaneous vaginal birth: Randomized
controlled trial.
AB - BACKGROUND: Ice-pack is widely used for alleviating postpartum perineal pain
sustained after birth related perineal trauma. However, it lacks robust evidence
on timing and frequency of applications, to ensure the effective and safe use of
this therapy. AIMS: To evaluate if a 10min ice-pack application relieved
postpartum perineal pain and if the analgesic effect was maintained for up to 2h.
METHODS: A randomised controlled trial conducted from December 2012 to February
2013 with 69 primiparous women >=18 years old, 6-24h postpartum, with perineal
pain >=3, who had not received anti-inflammatory medication or analgesics after
childbirth, who were randomised to a single ice-pack application on the perineum
for 10min or standard care. The primary and secondary outcomes were a reduction
>=30% in perineal pain intensity, immediately after the application and the
maintenance of the analgesic effect for up to 2h, respectively. FINDINGS:
Immediately post-intervention, the proportion of women whose perineal pain
decreased >=30% was significantly higher in the experimental group. Within 2h,
there was no significant difference in the pain levels in both groups. Within 2h,
for 61.9% and 89.3% of women in the experimental and control group, respectively,
the perineal pain levels remained unchanged. For the remaining participants,
perineal pain was increasing after an average time of 1h 45min and 1h 56min for
the experimental and control groups, respectively. CONCLUSION: By applying an ice
pack for 10min to the perineum, effective pain relief is achieved, that is
maintained for between 1h 45min and 2h.
PMID- 29337009
TI - Coherence and interlimb force control: Effects of visual gain.
AB - Neural coupling across hemispheres and homologous muscles often appears during
bimanual motor control. Force coupling in a specific frequency domain may
indicate specific bimanual force coordination patterns. This study investigated
coherence on pairs of bimanual isometric index finger force while manipulating
visual gain and task asymmetry conditions. We used two visual gain conditions
(low and high gain = 8 and 512 pixels/N), and created task asymmetry by
manipulating coefficient ratios imposed on the left and right index finger forces
(0.4:1.6; 1:1; 1.6:0.4, respectively). Unequal coefficient ratios required
different contributions from each hand to the bimanual force task resulting in
force asymmetry. Fourteen healthy young adults performed bimanual isometric force
control at 20% of their maximal level of the summed force of both fingers. We
quantified peak coherence and relative phase angle between hands at 0-4, 4-8, and
8-12 Hz, and estimated a signal-to-noise ratio of bimanual forces. The findings
revealed higher peak coherence and relative phase angle at 0-4 Hz than at 4-8 and
8-12 Hz for both visual gain conditions. Further, peak coherence and relative
phase angle values at 0-4 Hz were larger at the high gain than at the low gain.
At the high gain, higher peak coherence at 0-4 Hz collapsed across task asymmetry
conditions significantly predicted greater signal-to-noise ratio. These findings
indicate that a greater level of visual information facilitates bimanual force
coupling at a specific frequency range related to sensorimotor processing.
PMID- 29337011
TI - The genus Opisthacanthus Peters, 1861 (Scorpiones: Hormuridae), a remarkable
Gondwanian group of scorpions.
AB - New comments are proposed on the geographic distribution of genus Opisthacanthus,
and the Gondwanian model is further supported. The diversity of the genus is
extraordinary in Madagascar, with the same number of species as in continental
Africa, but sub-Saharan Africa is home to six out of the nine groups currently
recognized of Opisthacanthus. Given the affinities of the Opisthacanthus groups
and their current distribution, a center of origin in Africa could be favored for
these ancient scorpions. The proposed Gondwana model suggests that the Madagascar
Opisthacanthus are closer to those of the New World, which is consistent with the
affinities observed in morphological characters. A new species, Opisthacanthus
titanus sp. n., is described from the Torotorofotsy Forest, located in Eastern
Madagascar. The new species shows affinities with both Opisthacanthus
madagascariensis Kraepelin, 1894 known from dry regions in the western portion of
the island and Opisthacanthus lavasoa Lourenco, Wilme & Waeber, 2016 only known
from the extreme southeast of the island. The new species and O. madagascariensis
have similar external morphologies but the morphometric values are markedly
distinct. Moreover, O. madagascariensis is exclusively found in spiny forest
thickets and open woodlands, whereas the new species was found in the humid
forest of Torotorofotsy. The total number of species in Madagascar is now raised
to twelve. Biogeographical scenarios are also proposed to infer the origin of the
Opisthacanthus and better understand its distribution in the New World, in Africa
and Madagascar.
PMID- 29337010
TI - Protective effects of a radical scavenger edaravone on oligodendrocyte precursor
cells against oxidative stress.
AB - Oligodendrocyte precursor cells (OPCs) play critical roles in maintaining the
number of oligodendrocytes in white matter. Previously, we have shown that
oxidative stress dampens oligodendrocyte regeneration after white matter damage,
while a clinically proven radical scavenger, edaravone, supports oligodendrocyte
repopulation. However, it is not known how edaravone exerts this beneficial
effect against oxidative stress. Using in vivo and in vitro experiments, we have
examined whether edaravone exhibits direct OPC-protective effects. For in vivo
experiments, prolonged cerebral hypoperfusion was induced by bilateral common
carotid artery stenosis in mice. OPC damage was observed on day 14 after the
onset of cerebral hypoperfusion, and edaravone was demonstrated to decrease OPC
death in cerebral white matter. In vitro experiments also confirmed that
edaravone reduced oxidative-stress-induced OPC death. Because white matter damage
is a major hallmark of many neurological diseases, and OPCs are instrumental in
white matter repair after injury, our current study supports the idea that
radical scavengers may provide a potential therapeutic approach for white matter
related diseases.
PMID- 29337012
TI - Expanding the limits of endoscopic intraorbital tumor resection using 3
dimensional reconstruction.
AB - INTRODUCTION: Endoscopic orbital surgery is a nascent field and new tools are
required to assist with surgical planning and to ascertain the limits of the
tumor resectability. OBJECTIVE: We purpose to utilize three-dimensional
radiographic reconstruction to define the theoretical lateral limit of endoscopic
resectability of primary orbital tumors and to apply these boundary conditions to
surgical cases. METHODS: A three-dimensional orbital model was rendered in 4
representative patients presenting with primary orbital tumors using OsiriX open
source imaging software. A 2-Dimensional plane was propagated between the
contralateral nare and a line tangential to the long axis of the optic nerve
reflecting the trajectory of a trans-septal approach. Any tumor volume falling
medial to the optic nerve and/or within the space inferior to this plane of
resectability was considered theoretically resectable regardless of how far it
extended lateral to the optic nerve as nerve retraction would be unnecessary.
Actual tumor volumes were then superimposed over this plan and correlated with
surgical outcomes. RESULTS: Among the 4 lesions analyzed, two were fully medial
to the optic nerve, one extended lateral to the optic nerve but remained inferior
to the plane of resectability, and one extended both lateral to the optic nerve
and superior to the plane of resectability. As predicted by the three-dimensional
modeling, a complete resection was achieved in all lesions except one that
transgressed the plane of resectability. No new diplopia or vision loss was
observed in any patient. CONCLUSION: Three-dimensional reconstruction enhances
preoperative planning for endoscopic orbital surgery. Tumors that extend lateral
to the optic nerve may still be candidates for a purely endoscopic resection as
long as they do not extend above the plane of resectability described herein.
PMID- 29337013
TI - Inferior turbinectomy: what is the best technique?
PMID- 29337014
TI - The anatomic analysis of the vidian canal and the surrounding structures
concerning vidian neurectomy using computed tomography scans.
AB - INTRODUCTION: The type of endoscopic approach chosen for vidian neurectomy can be
specified by evaluating the vidian canal and the surrounding sphenoid sinus
structures. OBJECTIVE: The variations and morphometry of the vidian canal were
investigated, focusing on the functional correlations between them which are
crucial anatomical landmarks for preoperative planning. METHODS: This study was
performed using paranasal multidetector computed tomography images that were
obtained with a section thickening of 0.625mm of 250 adults. RESULTS: The
distributions of 500 vidian canal variants were categorized as follows; Type 1,
within the sphenoid corpus (55.6%); Type 2, partially protruding into the
sphenoid sinus (34.8%); Type 3, within the sphenoid sinus (9.6%). The
pneumatization of the pterygoid process is mostly seen in vidian canal Type 2
(72.4%) and Type 3 (95.8%) (p<0.001). The mean distances from the vidian canal to
the foramen rotundum and the palatovaginal canal were greater in the vidian canal
Type 2 and 3 with the pterygoid process pneumatization (p<0.001). The prevalence
of the intrasphenoid septum between the vidian canal and the vomerine crest and
lateral attachment which ending on carotid prominence were much higher in vidian
canal Type 3 than other types (p<0.001). The mean angle between the posterior end
of the middle turbinate and the lateral margin of the anterior opening of the
vidian canal was measured as 33.05+/-7.71 degrees . CONCLUSIONS: Preoperative
radiologic analysis of the vidian canal and the surrounding structures will allow
surgeons to choose an appropriate endoscopic approach to ensure predictable
postoperative outcomes.
PMID- 29337015
TI - Improved quantitative fatty acid values with correction of T2 relaxation time in
terminal methyl group: In vivo proton magnetic resonance spectroscopy at ultra
high field in hepatic steatosis.
AB - Proton magnetic resonance spectroscopy (MRS) with optimized relaxation time is an
effective method to quantify hepatic fatty acid values and characterize
steatosis. The aim of this study is to quantify the difference in hepatic lipid
content with metabolic changes during the progression of steatosis by using
localized MRS sequence with T2 relaxation time determination. Fatty liver disease
was induced in C57BL/6N mice through a high-fat diet (HFD) of pellets containing
60% fat, 20% protein, and 20% carbohydrates. We used stimulated echo acquisition
mode (repetition time: 3500 ms; mixing time: 10 ms; echo time: 20 ms) sequence.
Using enhanced and mono exponential curve-fitting methods, the lipid relaxation
time in mice was estimated at a fixed repetition time of 5000 ms and echo time
ranging from 20 to 70 ms. The calculated lipid contents with incorrect and
correct relaxation times were as follows: total saturated fatty acid (4.00 +/-
2.90 vs 6.74 +/- 2.25, p < 0.05 at week 0; 15.23 +/- 9.94 vs 25.53 +/- 10.49, p <
0.05 at week 4); total unsaturated fatty acid (0.40 +/- 0.49 vs 0.56 +/- 0.47, p
< 0.05 at week 4; 0.33 +/- 0.26 vs 0.60 +/- 0.21, p < 0.01 at week 7); total
unsaturated bond (0.48 +/- 0.52 vs 1.05 +/- 0.58, p < 0.05 at week 10).
Furthermore, we determined that the correct relaxation times of triglycerides
between 0 and 10 weeks were significantly altered in the resonances (~2.03 ppm:
31.07 +/- 1.00 vs 27.62 +/- 1.20, p < 0.01; ~2.25 ppm: 29.10 +/- 1.52 vs 26.39 +/
1.08, p < 0.05; ~2.78 ppm: 37.67 +/- 2.92 vs 29.37 +/- 2.64, p < 0.001). The
work presented focused on the significance of the J-coupling effect. The
selection of an appropriate relaxation time considering the J-coupling effect
provides an effective method for quantifying lipid contents and characterizing
hepatic steatosis.
PMID- 29337017
TI - Management of diabetes in older adults.
AB - Type 2 diabetes prevalence is high in older adults and is expected to rise in the
next decades. Diabetes in the population of frail older adults is accompanied by
functional disability, several comorbidities, and premature mortality. A
comprehensive geriatric assessment, including functional, cognitive, mental and
social status, is advisable for identifying the glycemic targets and glucose
lowering therapies, focused on patient preferences, needs, and risks. The
therapeutic options for older adults with diabetes are like those for the adult
population. However, the pharmacological treatments must be carefully prescribed
and monitored, taking into consideration the patient cognitive capacities, the
potentially life-threatening drug-drug interactions, the cardiovascular risk, and
with the main goal of avoiding hypoglycemia. Also, a careful nutritional
evaluation with appropriate tools, as well as a balanced and periodically
monitored physical activity, contribute to an effective tailored care plan, as
needed by older adults with diabetes. This review evaluates the currently
available hypoglycemic drugs and the current indications to the Italian
diabetology community, specifically with regard to the treatment of adults aged
75 years or older with diabetes, including the unmet needs by the guidelines.
PMID- 29337016
TI - Tear instability importance, mechanisms, validity and reliability of assessment.
AB - PURPOSE: To examine the factors which contribute to tear stability and the
validity and reliability of methods used for assessing tear break up time which
is a core part of an examination of tear stability in dry eye patients. METHODS:
A review of publications which are relevant to tear stability and its assessment.
RESULTS: Tear break up time may be more invasive than intended if difficulty
avoiding blinking during assessment results in reflex tearing. Notwithstanding
control of instilled volume and concentration of fluorescein, on-eye dilution is
highly variable according to resident tear volume. Blinking to evenly distribute
fluorescein may improve tear and lipid layer thickness so habitual tear function
is not assessed. Emphasis on a role for Meibomian gland dysfunction as a cause of
tear instability may be appropriate in many cases but ignores the roles for other
sources of tear lipid and other non-lipid contributions to tear instability such
as aqueous or mucus deficiency, desiccated epitheliopathy or anomalous blinking.
Objective less-invasive methods eliminate problems of inter-observer variability
and can reliably 'maintain vigilance' over wide areas of the tear layer. However
less-invasive results to date include mean tear break up findings which are both
shorter and longer than expected for normal controls. CONCLUSIONS: Fluorescein
tear break up time assessments cannot be standardised and less-invasive methods
are not yet standardised. Objective less-invasive and subjective fluorescein
break up time tests do not appear to be measuring the same tear phenomena
although both should be performed before other invasive procedures.
PMID- 29337018
TI - Prevalence of and secular trends in diagnosed diabetes in Italy: 1980-2013.
AB - BACKGROUND AND AIMS: The aim of this research was to examine the prevalence of
diabetes in Italy over a 34-year period. METHODS AND RESULTS: Self-reported
diabetes was assessed in eight health interview surveys of representative samples
of Italian population aged 20 years and over. Crude and standardised prevalence
were calculated by age, sex, educational level and area of residence. Logistic
models were fitted to calculate the contribution of age and BMI to the trend in
prevalence. In 2013 nearly 3.4 million Italians had a diagnosis of diabetes, more
than twice as many as in 1980. The crude prevalence of diabetes in men rose from
3.3% in 1980 to 7.1% in 2013 (+115%), and from 4.7% to 6.8% in women (+45%). The
prevalence was almost stable during the eighties, and started to rise from the
beginning of the nineties. One third of the increase in men and two thirds in
women is due to the ageing of the population, since the age-standardised
prevalence increased by 79% in men and 14% in women. The prevalence of overweight
and obesity increased less steeply than diabetes, and their contribution to the
trend in diabetes is less relevant than age. Prevalence rose more in the elderly,
in low-educated men, and in high-educated women. CONCLUSION: Given that the
ageing population plays a considerable role in explaining the trend, and that the
number of people in the oldest age groups will continue to grow, the rise in the
number of individuals with diabetes will represent a severe challenge for the
national health system.
PMID- 29337019
TI - Prediabetes is associated with microalbuminuria, reduced kidney function and
chronic kidney disease in the general population: The KORA (Cooperative Health
Research in the Augsburg Region) F4-Study.
AB - BACKGROUND AND AIMS: We investigated the associations of serum fasting (FG) and 2
h postload (2HG) glucose from an oral glucose tolerance test (OGTT), glycated
hemoglobin (HbA1c), fasting insulin and the homeostasis model assessment-insulin
resistance index (HOMA-IR) with urinary albumin-to-creatinine ratio (ACR) and
estimated glomerular filtration rate (eGFR). METHODS AND RESULTS: We performed
cross-sectional analyses of 2713 subjects (1429 women; 52.7%) without known type
2 diabetes, aged 31-82 years, from the KORA (Cooperative Health Research in the
Augsburg Region) F4-Study. FG, 2HG, HbA1c, fasting insulin, HOMA-IR and glucose
tolerance categories were analyzed for association with ACR and eGFR in
multivariable adjusted linear and median regression models, and with isolated
microalbuminuria (i-MA), isolated reduced kidney function (i-RKF) and chronic
kidney disease (CKD, defined as MA and/or RKF) in multivariable adjusted logistic
regression models. Among the 2713 study participants, 28% revealed prediabetes
(isolated impaired fasting glucose [i-IFG], isolated glucose tolerance [i-IGT] or
both by American Diabetes Association definition), 4.2% had unknown type 2
diabetes, 6.5% had i-MA, 3.1% i-RKF and 10.9% CKD. In multivariable adjusted
analysis, all continuous variables (FG, 2HG, HbA1c, fasting insulin and HOMA-IR)
were associated with i-MA, i-RKF and CKD. The odds ratios (ORs) for i-MA and CKD
were 1.54 (95% confidence interval: 1.02-2.33) and 1.58 (1.10-2.25) for
individuals with i-IFG. Moreover, the OR for i-RKF was 2.57 (1.31-5.06) for
individuals with IFG + IGT. CONCLUSION: Our findings suggest that prediabetes
might have harmful effects on the kidney.
PMID- 29337020
TI - Inverse association between plasma homocysteine concentrations and type 2
diabetes mellitus among a middle-aged and elderly Chinese population.
AB - BACKGROUND AND AIMS: Plasma homocysteine concentrations have been reported to be
associated with type 2 diabetes mellitus (T2DM) with controversial findings. The
aim of the present study was to investigate the association between plasma
homocysteine concentrations and T2DM. METHODS AND RESULTS: A cross-sectional
study including 19,085 eligible participants derived from the Dongfeng-Tongji
cohort was conducted. Plasma homocysteine concentrations were measured by Abbott
Architect i2000 Automatic analyzer and T2DM was defined according to American
Diabetes Association criteria. Logistic regression model was used to explore the
association between plasma homocysteine concentrations and T2DM. The prevalence
of T2DM was 19.0% in the whole population (mean age 62.9 years), 21.8% in males,
and 17.1% in females. In the multivariable logistic regression analyses, compared
with those in the lowest quintile, the OR (95% CI) of T2DM was 1.05 (0.92-1.21),
0.99 (0.86-1.14), 0.90 (0.78-1.05), and 0.77 (0.66-0.90) for quintile 2 to
quintile 5 of homocysteine concentrations after adjustment for potential
confounders (P for trend < 0.0001). Homocysteine concentrations were associated
with decreased T2DM prevalence risk (OR = 0.88 per SD increase of homocysteine
concentration; 95% CI: 0.84-0.93). A significant interaction between homocysteine
concentrations and drinking status on T2DM prevalence risk was observed (P for
interaction = 0.03). The inverse association of plasma homocysteine
concentrations with T2DM prevalence risk was observed in non-drinkers but not in
current drinkers. CONCLUSION: Plasma homocysteine concentrations were inversely
correlated with T2DM among a middle-aged and elderly Chinese population.
PMID- 29337021
TI - Changing Physical Activity Behavior in People With Multiple Sclerosis: A
Systematic Review and Meta-Analysis.
AB - OBJECTIVES: To (1) systematically review the literature on behavioral
interventions for people with multiple sclerosis (MS) that aim to change physical
activity (PA) behavior; and (2) explore whether these interventions are
clinically effective in improving PA, are theory based, and use established
behavior change techniques (BCTs). DATA SOURCES: A systematic electronic search
was conducted on databases EBSCO (including AMED, Biomedical Reference
Collection: Expanded, CINHAL, MEDLINE, PsycArticles, PsycInfo), PubMed, EMBASE,
and Web of Science from April 2017 to May 2017. STUDY SELECTION: Studies were
included if (1) the interventions aimed to change PA behavior among people with
MS; (2) PA was recognized as a primary outcome measure; and (3) they had a
randomized controlled trial (RCT) design. DATA EXTRACTION: The resulting
behavioral interventions were coded using the Theory Coding Scheme and the CALO
RE taxonomy to assess theory base and BCTs. A meta-analysis was conducted to
assess effectiveness. DATA SYNTHESIS: Fourteen RCTs were included. Combined,
there was a significant (P=.0003; d=1.00; 95% confidence interval, .46-1.53)
short-term change in self-report PA behavior for studies with nonactive control
groups. There was no change in objective or long-term PA. Studies failed to
discuss results in relation to theory and did not attempt to refine theory. Fifty
percent of BCTs within the CALO-RE were used, with BCTs of "goal-setting" and
"action-planning" being the most frequently used. CONCLUSIONS: Current evidence
supports the efficacy of PA intervention on subjective but not objective
outcomes. However, conclusions from this review should be interpreted with
caution because of the small number of studies included and small sample size.
Further, while using theory in intervention design, interventions in this review
have not reported the refining of theory. Exploration of the use of additional
BCTs to change PA behavior is also required within future interventions.
PMID- 29337022
TI - Reaction Time and Joint Kinematics During Functional Movement in Recently
Concussed Individuals.
AB - OBJECTIVE: To compare movement reaction time and joint kinematics between
athletes with recent concussion and matched control recreational athletes during
3 functional tasks. DESIGN: Cross-sectional. SETTING: Laboratory. PARTICIPANTS:
College-aged recreational athletes (N=30) comprising 2 groups (15 participants
each): (1) recent concussion group (median time since concussion, 126d; range, 28
432d) and (2) age- and sex-matched control group with no recent concussions.
INTERVENTIONS: We investigated movement reaction time and joint kinematics during
3 tasks: (1) jump landing, (2) anticipated cut, and (3) unanticipated cut. MAIN
OUTCOME MEASURES: Reaction time and reaction time cost (jump landing reaction
time-cut reaction time/jump landing reaction time*100%), along with trunk, hip,
and knee joint angles in the sagittal and frontal planes at initial ground
contact. RESULTS: There were no reaction time between-group differences, but the
control group displayed improved reaction time cost (10.7%) during anticipated
cutting compared with the concussed group (0.8%; P=.030). The control group
displayed less trunk flexion than the concussed group during the nondominant
anticipated cut (5.1 degrees difference; P=.022). There were no other kinematic
between-group differences (P>=.079). CONCLUSIONS: We observed subtle reaction
time and kinematic differences between individuals with recent concussion and
those without concussion more than a month after return to activity after
concussion. The clinical interpretation of these findings remains unclear, but
may have future implications for postconcussion management and rehabilitation.
PMID- 29337023
TI - The Effects of Functional Training, Bicycle Exercise, and Exergaming on Walking
Capacity of Elderly Patients With Parkinson Disease: A Pilot Randomized
Controlled Single-blinded Trial.
AB - OBJECTIVES: To compare the effects of functional training, bicycle exercise, and
exergaming on walking capacity of elderly with Parkinson disease (PD). DESIGN: A
pilot randomized, controlled, single-blinded trial. SETTING: A state reference
health care center for elderly, a public reference outpatient clinic for the
elderly. PARTICIPANTS: Elderly individuals (>=60 years of age; N=62) with
idiopathic PD (stage 2 to 3 of modified Hoehn and Yahr staging scale) according
to the London Brain Bank. INTERVENTION: The participants were randomly assigned
to three groups. Group 1 (G1) participated in functional training (n=22); group 2
(G2) performed bicycle exercise (n=20), and group 3 (G3) trained with Kinect
Adventures (Microsoft, Redmond, WA) exergames (n=20). MAIN OUTCOME MEASURES: The
primary outcome measure was the 6-minute walk test (6MWT); secondary outcome
measures were the 10-m walk test (10MWT), sitting-rising test (SRT), body mass
index, Parkinson Disease Questionnaire-39, World Health Organization Disability
Assessment Schedule 2.0 (WHODAS 2.0), and 15-item Geriatric Depression Scale.
RESULTS: All groups showed significant improvements in 6MWT (G1 P=.008; G2
P=.001; G3 P=.005), SRT (G1 P<.001; G2 P=.001; G3 P=.003), and WHODAS 2.0 (G1
P=.018; G2 P=.019; G3 P=.041). Only G3 improved gait speed in 10MWT (P=.11). G1
(P=.014) and G3 (P=.004) improved quality of life. No difference was found
between groups. CONCLUSIONS: Eight weeks of exergaming can improve the walking
capacity of elderly patients with PD. Exergame training had similar outcomes
compared with functional training and bicycle exercise. The three physical
exercise modalities presented significant improvements on walking capacity,
ability to stand up and sit, and functionality of the participants.
PMID- 29337024
TI - Moderators of Treatment Outcomes After Telehealth Self-Management and Education
in Adults With Multiple Sclerosis: A Secondary Analysis of a Randomized
Controlled Trial.
AB - OBJECTIVE: To examine moderators of treatment effects in a randomized controlled
trial comparing a telehealth self-management intervention with a telehealth
multiple sclerosis (MS) education intervention for fatigue, pain, and mood in
adults with MS. DESIGN: Secondary analysis of a single-blind randomized
controlled trial. SETTING: Community. PARTICIPANTS: Adults with MS and chronic
fatigue, chronic pain, and/or moderate depressive symptoms (N=163) recruited from
across the United States. INTERVENTIONS: Two 8-week, telephone-delivered symptom
interventions delivered 1:1: a self-management intervention (n=75) and an MS
education intervention (n=88). MAIN OUTCOME MEASURES: Outcome measures were
fatigue impact pain interference, and depressive symptom severity assessed at
baseline and posttreatment. Potential moderators of treatment effects assessed at
baseline were demographics (age, sex, and education), clinical characteristics
(disease duration and disability severity), symptoms (perceived cognitive
impairment and pain intensity), baseline levels of the treatment outcomes (pain
interference, fatigue impact and depressive symptom severity), and cognitive
behavioral factors (pain catastrophizing, fatigue catastrophizing, self-efficacy,
and patient activation). RESULTS: Moderation analyses found significant
moderation for fatigue impact but not for pain intensity or depressive symptom
severity. Baseline patient activation interacted with treatment group to predict
fatigue impact at posttreatment (P=.049). Among participants with high baseline
patient activation, the self-management group reported significantly less fatigue
at posttreatment than the education group. No other variables moderated the study
outcomes. CONCLUSIONS: At the group level, participants responded to both
interventions, regardless of disease characteristics, demographics, symptom
levels, and cognitive behavioral factors. Self-management and education are both
potentially beneficial symptom treatments that may be recommended to individuals
with MS and chronic pain, fatigue, and/or depressive symptoms.
PMID- 29337025
TI - Hepatosplenic T-cell Lymphoma: a review of clinicopathologic features,
pathogenesis, and prognostic factors.
AB - Hepatosplenic T-cell lymphoma (HSTCL) is a rare and clinically aggressive type of
T-cell lymphoma that arises most often in adolescents and young adults. Patients
with HSTCL commonly present with B-symptoms and cytopenias, which may suggest a
diagnosis of acute leukemia initially. Patients present with extranodal disease
involving the spleen, liver and bone marrow; lymphadenopathy is usually absent.
The lymphoma cells can show a spectrum of cell sizes and are of T-cell lineage,
often negative for CD4 and CD8 and positive for T-cell receptor gammadelta or,
less often, alphabeta. Recent studies have identified gene mutations in oncogenic
pathways that are likely involved in pathogenesis and may be targets for therapy.
Mutations in STAT3 or STAT5B lead to activation of the JAK/STAT pathway, and
mutations involving SETD2, IN080 and ARID1 are involved in chromatin
modification. Currently, there is no consensus standard of care for HSTCL
patients, although several studies support a role for allogeneic hematopoietic
stem cell transplant. Although patients with HSTCL are best treated in the
context of clinical trials, the rarity of these neoplasms likely necessitates a
multi-institutional approach. In this review, we focus on the clinicopathologic
and genetic characteristics of HSTCL. We also discuss the differential diagnosis
and therapeutic approaches.
PMID- 29337026
TI - Effect of recombinant human growth hormone on rotator cuff healing after
arthroscopic repair: preliminary result of a multicenter, prospective,
randomized, open-label blinded end point clinical exploratory trial.
AB - BACKGROUND: This study evaluated the effect of systemic injection of recombinant
human growth hormone (rhGH) on outcomes after arthroscopic rotator cuff repair.
METHODS: This multicenter, prospective, randomized, comparative trial, randomized
patients who underwent arthroscopic repair of large-sized rotator cuff tears into
3 groups: rhGH 4 mg group (n = 26), rhGH 8 mg group (n = 24) , and control group
(n = 26). Sustained release rhGH was injected subcutaneously once weekly for 3
months postoperatively. The healing failure rate (primary end point), fatty
infiltration, and atrophy of the supraspinatus muscle, and functional scores
(Constant and American Shoulder and Elbow Surgeons scores) were evaluated at 6
months. Range of motion, pain visual analog scale, and serum insulin-like growth
factor-1 level were measured at each follow-up. RESULTS: The healing failure rate
was similar between groups (rhGH 4 mg group, 30.8%; rhGH 8 mg group, 16.7%; and
control group, 34.6%; all P > .05) The proportion of severe fatty infiltration
(Goutallier grade >=3) was 20.8% in the rhGH 8 mg group, 23.1% in the rhGH 4 mg
group, and 34.6% in the control group (P > .05). Functional outcomes, range of
motion, and pain visual analog scale were similar between groups (all P > .05).
The rhGH 8 mg group showed more increased peak insulin-like growth factor-1 level
(279.43 ng/mL) than the rhGH 4 mg group ((196.82 ng/mL) and control group (186.31
ng/mL), which was not statistically different (all P > .05). No rhGH injection
related major safety issues occurred. CONCLUSIONS: This preliminary study showed
no statistically significant improvement in healing or outcomes related to the
treatment of rhGH after rotator cuff repair. However, further study with more
enrolled patients after resetting the rhGH dose or daily administration protocol
would be mandatory.
PMID- 29337027
TI - An assessment of proximal humerus density with reference to stemless implants.
AB - BACKGROUND: Shoulder arthroplasty humeral components have undergone several
generational changes, with systems now offering shorter stems and stemless
options. The stemless humeral implants obtain fixation in the trabecular bone of
the proximal humerus through elaborate fixation features. To optimize implant
design, the regional variations in bone density within the proximal humerus
should be determined. As such, the purpose of this computed tomography-based
study was to map the regional variations in bone density of the proximal humerus.
METHODS: The trabecular-canal of the proximal humerus was extracted from computed
tomography scans of 98 subjects and divided into 13 slices and 5 subsections
(central, anterior, posterior, medial, and lateral). The average apparent density
(rhoAVG) was then quantified in each subsection of the trabecular-canal. RESULTS:
Slice depth, subsection, and gender were all significant main effects, with
additional significant interactions between slice depth, subsection, and
osteoarthritic condition. The slices above the resection plane had the greatest
rhoAVG, with densities decreasing down the canal. The central subsection had
significantly lower rhoAVG than the peripheral sections, and the medial
subsection tended to have the highest rhoAVG (P < .001). Furthermore, the rhoAVG
of male subjects was significantly greater than that of female subjects (P <
.001). CONCLUSIONS: The apparent density of the proximal humerus' trabecular
canal is nonuniform. This has implications for the design of stemless implants,
indicating that implants seeking purchase in higher density bone should take
advantage of the peripheral regions of the trabecular-canal within the first 15
20 mm beneath the humeral head resection plane.
PMID- 29337028
TI - Bipolar pedicled teres major transfer for irreparable subscapularis tendon tears:
an anatomic feasibility study.
AB - BACKGROUND: Subscapularis (SSC) tendon tears are a challenging problem because
they can significantly alter shoulder mechanics and function. Tendon retraction
and advanced fatty degeneration associated with a chronic tear may make it
irreparable. Tendon transfers options for such tears are viable, but results in
the setting of associated glenohumeral instability are inconsistent. With the
potential to recreate the SSC line of pull, the teres major (TM) may be a viable
option for transfer. This cadaveric study investigated the feasibility and
outlined the steps of a bipolar, pedicled TM transfer for irreparable SSC tendon
tears. METHODS: Eight fresh frozen cadaver torsos from 4 women and 4 men (average
age, 84 years; range, 68-96 years) were dissected. Anatomic details comparing TM
to SSC were examined, including muscle width, length, thickness, and line of pull
in the scapular plane. In addition, a surgical technique was described for
implementing the pedicled TM transfer. RESULTS: Measurements between the TM and
SSC were comparable, with the exception of muscle belly width, which was
significantly greater in the SSC. With transfer of the TM, there was no
impingement or tension on the brachial plexus or the neurovascular pedicle of the
TM. The line of pull of the TM relative to the SSC had a difference of 9 degrees
. CONCLUSIONS: This study demonstrates that a bipolar TM tendon transfer is an
anatomically feasible option for reconstruction of an irreparable SSC tendon
tear. Further clinical studies are necessary to understand its outcome in in vivo
conditions.
PMID- 29337029
TI - Arthroscopic Latarjet procedure with double-button fixation: short-term
complications and learning curve analysis.
AB - BACKGROUND: The arthroscopic Latarjet with double-button fixation is a guided
procedure recently proposed to treat anterior shoulder instability with glenoid
bone loss. The goal of this study was to report intraoperative and early
postoperative complications and to analyze the learning curve. METHODS: This was
a prospective, nonrandomized study that included 88 patients. Intraoperative or
postoperative complications as well as adverse events and operative time were
recorded. Clinical outcomes were evaluated at 2 weeks, 1.5 months, and at the
last follow-up. Radiologic analysis was based on an immediate postoperative
computed tomography scan. RESULTS: The intraoperative complications or adverse
events rate was 3.3%: 1 conversion to open surgery, 1 bone block fracture, and 1
instrumentation problem. The postoperative complication rate was 6.8%: 4 coracoid
migrations, and 2 subluxations. None of these complications occurred beyond the
10th case performed. The average operative time significantly decreased with
surgical experience (r = -0.8426; 95% confidence interval, -0.9074 to -0.7384; P
< .0001) to reach 76 +/- 12 minutes (range, 62-95 minutes) at 30 cases.
Radiologically, 90% of the bone blocks were flush and subequatorial beyond the
30th case. At a mean follow-up of 12.6 months (range, 6-24 months), Walch-Duplay
and Rowe scores were 80 and 81 points, respectively. CONCLUSIONS: At short-term
follow-up, the arthroscopic Latarjet procedure with double-button fixation
exhibited a low complication rate. Operative time significantly improved with
surgical experience and was optimized after 30 cases. Early clinical results
confirmed that this procedure can be safe and reliable.
PMID- 29337030
TI - Nasal IL-25 predicts the response to oral corticosteroids in chronic
rhinosinusitis with nasal polyps.
PMID- 29337031
TI - Does vagus nerve stimulation influence pregnancy outcomes?
PMID- 29337032
TI - Biohydrogen fermentation of galactose at various substrate concentrations in an
immobilized system and its microbial correspondence.
AB - The effects of substrate concentration on fermentative hydrogen production from
galactose at a fixed hydraulic retention time of 12 h were investigated in an
immobilized continuously stirred tank reactor. Peak hydrogen production rate and
hydrogen yield of 9.57 L/L-d and 1.10 mol/mol galactoseadded, respectively, were
obtained at a feed substrate concentration of 30 g/L and an organic loading rate
of 60 L/L-d. Quantitative polymerase chain reaction analysis showed that the
variations in the performance resulted primarily from metabolic alterations
within the metabolism of the established microbial community rather than
modifications in the population. The results obtained showed that optimal
substrate concentration is essential for the efficient, continuous production of
hydrogen from galactose.
PMID- 29337033
TI - Gliclazide, a KATP channel blocker, inhibits vascular smooth muscle cell
proliferation through the CaMKKbeta-AMPK pathway.
AB - Gliclazide, a sulfonylurea that is widely used to treat type II-diabetes,
specifically blocks KATP channels and recombinant smooth muscle (SUR2B/Kir6.1)
KATP channels with high potency. Furthermore, it exerts antioxidant properties
and inhibits tumor cell proliferation. In this study, we investigated the
inhibitory effect of gliclazide on vascular smooth muscle cell (VSMC)
proliferation and tried to identify the underlying signaling pathway. We first
investigated the effect of gliclazide-induced AMP-activated protein kinase (AMPK)
activation on the proliferation of VSMCs. Gliclazide induced phosphorylation of
AMPK in a dose- and time-dependent manner and inhibited VSMC proliferation
following stimulation by platelet-derived growth factor (PDGF). However, KATP
channel openers and Kir6.1 siRNA prevented gliclazide-mediated inhibition of VSMC
proliferation. Gliclazide also increased the levels of Ca2+/calmodulin-dependent
protein kinase kinase beta (CaMKKbeta), an upstream kinase of AMPK. These
findings suggested that the effects of KATP channels on AMPK activity were
mediated by the regulation of intracellular Ca2+ levels. Oral administration of
2mg/kg gliclazide resulted in the activation of CaMKKbeta and AMPK in vivo,
suggesting that gliclazide suppressed VSMC proliferation via the CaMKKbeta-AMPK
signaling pathway. Taken together, our observations indicated that gliclazide
induced AMPK activation may act to prevent diabetes-associated atherosclerosis.
PMID- 29337034
TI - Establishment of trimester-specific reference range for thyroid hormones during
pregnancy.
AB - OBJECTIVE: Physiological gestational changes are associated with alterations in
thyroid function which require different biochemical interpretation from that of
non-pregnant women and necessitate established pregnancy-specific reference
ranges. We aimed to identify the trimester-specific ranges of thyroid markers in
a healthy population of pregnant Iranian women. METHODS: In this self-sequential
study, data were extracted from The Tehran Thyroid and Pregnancy Study; a total
of 314 women were tested during the 1st, 2nd and 3rd trimesters for serum levels
of thyrotropin (TSH), thyroxine (T4), free thyroxine index (FT4I) and thyroid
peroxidase antibody (TPOAb). Trimester-specific reference intervals for TSH, T4
and FT4I and first trimester reference range for TPOAb were estimated. The normal
and modulus exponential-normal models were fitted by maximum likelihood using
STATA software. The 2.5th and 97.5th percentiles of thyroid parameters were
determined and used as reference intervals. RESULTS: Mean+/-SD age of
participants was 26.8+/-5.2years. Estimated reference intervals for TSH, T4 and
FT4I in the 1st, 2nd and 3rd trimesters corresponding to the 2.5th and 97.5th
percentiles were 0.14-6.14, 0.43-4.64, 0.63-3.9MUIU/ml; 78.01-215.19, 93.23
243.87, 89.61-211.37nmol/L; and 1.73-4.53, 1.96-5.64, 1.72-4.30, respectively.
Reference interval for TPOAb in the 1st trimester was 1.40-38.02IU/mL. Median of
TSH was low in the 1st trimester, and gradually increased until 2nd trimester,
followed by a slight decrease onward. A decreasing trend in TSH levels was
observed in higher centiles with advancing gestational age. CONCLUSION: This
study provides trimester-specific reference ranges for some common thyroid
markers among healthy Iranian women in an iodine sufficient area, to prevent
biochemical misinterpretations during pregnancy.
PMID- 29337035
TI - Early Warning Scores do not accurately predict mortality in sepsis: A meta
analysis and systematic review of the literature.
AB - OBJECTIVES: Early Warning Scores are used to evaluate patients in many hospital
settings. It is not clear if these are accurate in predicting mortality in
sepsis. We performed a systematic review and meta-analysis of multiple studies in
sepsis. Our aim was to estimate the accuracy of EWS for mortality in this
setting. METHODS: PubMED, CINAHL, Cochrane, Web of Science and EMBASE were
searched to October 2016. Studies of adults with sepsis who had EWS calculated
using any appropriate tool (e.g. NEWS, MEWS) were eligible for inclusion. Study
quality was assessed using QUADAS-2. Summary estimates were derived using HSROC
analysis. RESULTS: Six studies (4298 participants) were included. Results suggest
that EWS cannot be used to predict which patients with sepsis will (positive
likelihood ratio 1.79, 95% CI 1.53 to 2.11) or will not die (negative likelihood
ratio 0.59, 95% CI 0.45 to 0.78). Two studies were rated as low risk of bias and
one as unclear risk of bias on all domains. The other three studies were judged
at high risk of bias in one domain. CONCLUSION: Early Warning Scores are not
sufficiently accurate to rule in or rule out mortality in patients with sepsis,
based on the evidence available, which is generally poor quality.
PMID- 29337036
TI - Potential of real-time PCR threshold cycle (CT) to predict presence of free toxin
and clinically relevant C. difficile infection (CDI) in patients with cancer: A
reply.
PMID- 29337037
TI - Synthesis of new sarsasapogenin derivatives with antiproliferative and apoptotic
effects in MCF-7 cells.
AB - Sarsasapogenin, a kind of mainly effective component of Anemarrhena asphodeloides
Bunge, possesses good antitumor properties. Two series of new sarsasapogenin
derivatives were synthesized and evaluated for their cytotoxicities against three
human cancer cell lines (HepG2, A549, MCF-7) using the MTT assay. The structure
activity relationship revealed that the N, N-dimethylamino, pyrrolidinyl, and
imidazolyl substituted at the C26 position could increase the antitumor efficacy
of the 3-oxo sarsasapogenin series of compounds. Compound 4c with pyrrolidinyl
substituted at the C26 position exhibited the greatest cytotoxic activity against
MCF-7 cell line (IC50 = 10.66 MUM), which was 4.3-fold more potent than
sarsasapogenin. Action mechanism investigations showed that 4c could inhibit the
colony formation and induce the apoptosis of MCF-7 cells. Further researches
showed that a decrease in mitochondrial membrane potential and increases in the
expression level of cleaved-PARP and the ratio of Bax/Bcl-2 were observed in MCF
7 cells after treatment with 4c, suggesting that the mitochondrial pathway was
involved in the 4c-mediated apoptosis. These results show that compound 4c may
serve as a lead for further optimization.
PMID- 29337038
TI - Back to the future: Epigenetic clock plasticity towards healthy aging.
AB - Aging is the most important risk factor for major human lifestyle diseases,
including cancer, neurological and cardiometabolic disorders. Due to the complex
interplay between genetics, lifestyle and environmental factors, some individuals
seem to age faster than others, whereas centenarians seem to have a slower aging
process. Therefore, a biochemical biomarker reflecting the relative biological
age would be helpful to predict an individual's health status and aging disease
risk. Although it is already known for years that cumulative epigenetic changes
occur upon aging, DNA methylation patterns were only recently used to construct
an epigenetic clock predictor for biological age, which is a measure of how well
your body functions compared to your chronological age. Moreover, the epigenetic
DNA methylation clock signature is increasingly applied as a biomarker to
estimate aging disease susceptibility and mortality risk. Finally, the epigenetic
clock signature could be used as a lifestyle management tool to monitor healthy
aging, to evaluate preventive interventions against chronic aging disorders and
to extend healthy lifespan. Dissecting the mechanism of the epigenetic aging
clock will yield valuable insights into the aging process and how it can be
manipulated to improve health span.
PMID- 29337040
TI - Colonic perforation due to GI histoplasmosis in an immunocompetent host mimicking
Crohn's disease.
PMID- 29337039
TI - Patients with small and diminutive proximal hyperplastic polyps have higher rates
of synchronous advanced neoplasia compared with patients without serrated
lesions.
AB - BACKGROUND AND AIMS: The association of proximal small and diminutive
hyperplastic polyps (HPs) with synchronous advanced neoplasia is not well
defined. However, sessile serrated polyps (SSPs), even when small, are known to
portend a risk of synchronous neoplasia. Currently, the U.S. Multi-Society Task
Force on Colorectal Cancer does not recommend a change in the surveillance
interval when proximal small HPs are detected. We aimed to compare the rates of
synchronous advanced neoplasia in a screening colonoscopy cohort of patients with
small and then diminutive proximal HPs in comparison, first to a cohort absent
any serrated or proximal HPs and then in comparison with a cohort with small
proximal SSPs. METHODS: Consecutive screening colonoscopies were recorded between
2005 and 2010 at an academic medical center. Patients were divided into 3
mutually exclusive groups. Group 1 consisted of patients with at least 1 HP that
was proximal to the sigmoid colon, <1 cm in endoscopic size, and up to 3 total
HPs in number. Group 2 included patients without any proximal HPs or SSPs. Group
3 consisted of patients with 1 to 2 SSPs, with at least 1 being proximal to the
sigmoid colon, that were <1 cm in endoscopic size and without dysplasia. Rates of
synchronous advanced neoplasia in patients with small (<1 cm) and diminutive (<=5
mm) proximal HPs were compared with the rates for the other 2 groups. RESULTS:
There were 482 of 2569 patients (18.8%) with a small proximal HP who met the
criteria for Group 1. The rate of synchronous advanced neoplasia in patients with
a small proximal HP (61/482, 12.7%) was significantly greater compared with the
average risk in the non-serrated cohort (Group 2, 133/1878, 7.1%; P < .001).
There was no significant difference in the rate of synchronous advanced neoplasia
when the small proximal HP group was subdivided by size (<=5 mm, 51/404, 12.6% vs
6-9 mm, 10/78, 12.8%; P = 1.00). The rate of synchronous advanced neoplasia in
patients with diminutive (<=5 mm) proximal HPs (51/404, 12.6%) was not
significantly different from the rate observed with proximal SSPs of similar size
(17/113, 15.0%; P = .529). CONCLUSION: Patients with small and diminutive
proximal HPs tend to harbor higher rates of synchronous advanced neoplasia
compared with those without any serrated lesions detected on screening
colonoscopy. Surveillance outcomes for metachronous advanced neoplasia for
patients with small proximal HPs deserves further study. The synchronous advanced
neoplasia rate in patients with proximal diminutive HPs is similar to that of
proximal diminutive SSPs and could have implications in a resect and discard
strategy.
PMID- 29337041
TI - Provision of abortion and other reproductive health services among former Midwest
Access Project trainees.
AB - OBJECTIVE: The Midwest Access Project (MAP) offers opt-in training to students,
residents and practicing clinicians in reproductive health care including
abortion. We surveyed MAP alumni to identify current practice characteristics and
assess predictors of reproductive health service provision. STUDY DESIGN: We sent
an online survey to alumni of MAP's Individual Clinical Training program, 2007
2015 (n=127). The primary outcome was current provision of any abortion service.
Secondary outcomes included providing specific abortion services and other
reproductive services. RESULTS: We received responses from 61% of eligible MAP
alumni (n=77 out of 127). The majority reported a specialty of Family Medicine
(68%) and current location in the Midwest (52%). Among current residents, fellows
or clinicians practicing in a field whose scope includes abortion (n=56), 50%
provide abortion. Most (84%) provide outpatient miscarriage management, and
nearly all (>=96%) provide pregnancy options counseling and full scope
contraception. Respondents who received the most advanced training in medication
abortion as part of their MAP training were more likely to report providing
abortion in their current practice than those who did not (63% vs. 32%, p=.027),
as were those who completed more than one MAP rotation compared to those who
completed one rotation (100% vs. 44%, p=.009). CONCLUSIONS: Half of MAP's alumni
provide some abortion care. Nearly all provide comprehensive counseling and
contraceptive services. IMPLICATIONS: Opt-in training is a promising strategy to
develop providers of comprehensive reproductive health care.
PMID- 29337042
TI - Endovascular recanalization for nonmalignant obstruction of the inferior vena
cava.
AB - OBJECTIVE: The aim of this study was to evaluate outcomes of endovascular
recanalization of the inferior vena cava (IVC) and iliac veins with long-standing
chronic venous obstruction caused by nonmalignant disease. METHODS: Medical
records for 66 patients who underwent endovascular recanalization of the IVC with
or without iliac veins from January 2001 to December 2014 at our medical center
were retrospectively reviewed. Primary outcomes included morbidity and mortality;
secondary outcomes included primary, primary assisted, and secondary patency and
resolution of symptoms. RESULTS: Forty-five (68%) patients were male; the mean
age was 43 years (range, 17-83 years). All but one patient had chronic symptoms
(mean duration, 8 +/- 9 years). Clinical, Etiology, Anatomy, and Pathophysiology
classes included 3, 4a, 4b, 5, and 6 in 41, 2, 1, 2, and 20 patients,
respectively. Mean Venous Clinical Severity Score was 12.4 +/- 6.5. Fifty-nine
patients (89%) had history of deep venous thrombosis, and 13 also had pulmonary
embolism. Twenty-five patients (38%) had an IVC filter; 20 (30%) had
thrombophilia. The obstruction involved the infrarenal IVC in 44 patients and
both the infrarenal and suprarenal IVC in 22 patients. All recanalizations were
performed under conscious sedation and local anesthesia and involved sequential
angioplasty and stent placement into the IVC, with or without iliac vein
stenting. Venous access included bilateral femoral veins and right internal
jugular vein. Stents used were Wallstents (Boston Scientific, Marlborough, Mass;
n = 70), Protege stents (ev3, Plymouth, Minn; n = 49), Gianturco (Cook Medical,
Bloomington, Ind; n = 44), and Luminexx (Bard, Tempe, Ariz; n = 1). Pressure
gradients were 6.7 +/- 4.0 mm Hg before and 0.9 +/- 1.1 mm Hg after stenting (P <
.001). Procedural success was 90% and 100% at first and second attempt at
recanalization, respectively. There was no mortality or clinically significant
pulmonary embolism. Four patients had five complications: two developed an
arteriovenous fistula, one patient developed groin hematoma that required open
evacuation, and one had peri-IVC hematoma and femoral vein thrombosis that
required repeated angioplasty and stenting; 93% of patients received long-term
anticoagulation. Follow-up was 42 +/- 36 months. Four patients were lost to
follow-up. Primary patency, primary assisted patency, and secondary patency at 36
months were 78%, 87%, and 91%, respectively. Symptoms resolved in 83% of
patients. On multivariable regression analysis, hypercoagulable state was the
only predictor of reocclusion of the recanalized veins. CONCLUSIONS: Endovascular
recanalization for nonmalignant symptomatic IVC and associated iliofemoral venous
obstruction with balloon angioplasty and self-expanding stents is technically
challenging; however, it is safe and durable. In our retrospective study,
estimated patency rates at 36 months were >85%, and clinical outcomes were
excellent. Venous stenting should be attempted for chronic nonmalignant IVC and
associated iliac or iliofemoral venous obstructions before open surgical
reconstruction is contemplated.
PMID- 29337043
TI - Membrane-permeable Rab27A is a regulator of the acrosome reaction: Role of
geranylgeranylation and guanine nucleotides.
AB - The acrosome reaction is the regulated exocytosis of mammalian sperm's single
secretory granule, essential for fertilization. It relies on small GTPases, the
cAMP binding protein Epac, and the SNARE complex, among other components. Here,
we describe a novel tool to investigate Rab27-related signaling pathways: a
hybrid recombinant protein consisting of human Rab27A fused to TAT, a cell
penetrating peptide. With this tool, we aimed to unravel the connection between
Rab3, Rab27 and Rap1 in sperm exocytosis and to deepen our understanding about
how isoprenylation and guanine nucleotides influence the behaviour of Rab27 in
exocytosis. Our results show that TAT-Rab27A-GTP-gamma-S permeated into live
sperm and triggered acrosomal exocytosis per se when geraylgeranylated but
inhibited it when not lipid-modified. Likewise, an impermeant version of Rab27A
elicited exocytosis in streptolysin O-permeabilized - but not in non
permeabilized - cells when geranylgeranylated and active. When GDP-beta-S
substituted for GTP-gamma-S, isoprenylated TAT-Rab27A inhibited the acrosome
reaction triggered by progesterone and an Epac-selective cAMP analogue, whereas
the non-isoprenylated protein did not. Geranylgeranylated TAT-Rab27A-GTP-gamma-S
promoted the exchange of GDP for GTP on Rab3 and Rap1 detected by far
immunofluorescence with Rab3-GTP and Rap1-GTP binding cassettes. In contrast, TAT
Rab27A lacking isoprenylation or loaded with GDP-beta-S prevented the activation
of Rab3 and Rap1 elicited by progesterone. Challenging streptolysin O
permeabilized human sperm with calcium increased the population of sperm with
Rap1-GTP, Rab3-GTP and Rab27-GTP in the acrosomal region; pretreatment with anti
Rab27 antibodies prevented the activation of all three. The novel findings
reported here include: the description of membrane permeant TAT-Rab27A as a
trustworthy tool to unveil the regulation of the human sperm acrosome reaction by
Rab27 under physiological conditions; that the activation of endogenous Rab27 is
required for that of Rab3 and Rap1; and the connection between Epac and Rab27 and
between Rab27 and the configuration of the SNARE complex. Moreover, we present
direct evidence that Rab27A's lipid modification, and activation/inactivation
status correlate with its stimulatory or inhibitory roles in exocytosis.
PMID- 29337044
TI - Lysophosphatidic acid regulates the motility of MCF10CA1a breast cancer cell
sheets via two opposing signaling pathways.
AB - Aberrant cell migration leads to the dispersal of malignant cells. The ubiquitous
lipid mediator lysophosphatidic acid (LPA) modulates cell migration and is
implicated in tumor progression. Yet, the signaling cascades that regulate LPA's
effect on cell motility remain unclear. Using time-lapse imaging and quantitative
analyses, we studied the role of signaling cascades that act downstream of LPA on
the motility of MCF10CA1a breast cancer cells. We found that LPA alters cell
motility via two major signaling pathways. The Rho/ROCK signaling cascade is the
predominant pathway that increases E-Cadherin containing cell-cell adhesions and
cortical arrangement of actomyosin to promote slow, directional, spatially
coherent and temporally consistent movement. In contrast, Galphai/o- and
Galphaq/11-dependent signaling cascades lessen directionality and support the
independent movement of cells. The net effect of LPA on breast cancer cell
migration therefore results from the integrated signaling activity of the
Rho/ROCK and Galphai/o- and Galphaq/11-dependent pathways, thus allowing for a
dynamic migratory response to changes in the cellular or microenvironmental
context.
PMID- 29337045
TI - Increased dendritic length in CA1 and CA3 hippocampal neurons during the
metestrus phase in Wistar rats.
AB - Studies have shown that changes in ovarian hormone concentrations promote natural
fluctuations in the density of dendritic spines of hippocampal neurons in female
Sprague-Dawley rats, without changes in dendritic length, throughout the estrous
cycle. However, it is still unknown whether these fluctuations are present in
other rat strains. Due to our interest in Wistar rats, the objective of the
present study was to determine if there is natural dendritic remodeling in the
female Wistar rat throughout the estrous cycle. This study analyzed the dendritic
arborization of pyramidal neurons CA1 and CA3 of the dorsal hippocampus in each
phase of the estrous cycle. We used the Golgi-Cox staining method and Sholl
analysis to evaluate the dendritic length and density of dendritic spines. Our
results showed that the dendritic length of the basilar and apical trees of CA1
neurons was longer in the metestrus phase. In CA3 neurons, only the apical
dendritic trees showed longer dendritic length during metestrus. There was no
variation in the density of dendritic spines in relation to any of the phases of
the estrous cycle. Taken together, these results indicated that pyramidal neurons
of the CA1 and CA3 regions of the dorsal hippocampus in the Wistar rat exhibited
changes in dendritic length in the metestrus phase of the estrous cycle.
Together, these data are important when considering the use of these organisms in
behavioral studies.
PMID- 29337046
TI - The impact of fast track protocols in upper gastrointestinal surgery: A meta
analysis of observational studies.
AB - BACKGROUND: Fast track surgery has been implemented in colorectal procedures
during the last decade and is accompanied by significant improvement in patient
outcomes during the early postoperative period. However, to date, its adoption in
upper gastrointestinal surgery remains a matter of debate. In this context, we
aimed to summarize the existing evidence in the international literature.
MATERIALS AND METHODS: We searched Medline, Scopus, ClinicalTrials.gov and
Cochrane Central Register databases for published randomized controlled trials.
The meta-analysis was performed with the RevMan 5.3.5 software. MAIN FINDINGS:
Thirty studies were finally included in the present meta-analysis. The post
operative morbidity was not influenced by the implementation of fast track
surgery (FTS) (OR 0.84, 95% CI 0.64-1.09). However, in cases treated with
laparoscopic surgery fast track surgery seemed to reduce morbidity by 50% (p =
.006). The overall mortality of patients was low in the majority of included
studies and was not influenced by fast track surgery (OR 1.12, 95% CI 0.50-2.52).
The duration of postoperative hospitalization was significantly reduced with the
adoption of FTS (MD -2.24, 95% CI -2.63 to -1.85 days). Concurrently, the overall
cost was significantly reduced in cases treated with FTS (MD -982.30, 95% CI
1367.68 to -596.91 U.S dollars). CONCLUSION: According to the findings of our
meta-analysis suggest that FTS seems to be safe in patients undergoing upper
gastrointestinal surgery and reduce both the days of postoperative
hospitalization and the overall cost. This observation should be taken into
account in future recommendations to enhance the implementation of FTS protocols
in current clinical practice.
PMID- 29337047
TI - Imaging flow cytometry: A method for examining dynamic native FOXO1 localization
in human lymphocytes.
AB - While flow cytometry can reliably assess surface and intracellular marker
expression within small cell populations, it does not provide any information on
protein localization. Several key transcription factors (TF) downstream of
lymphocyte surface receptors are regulated by nuclear versus cytoplasmic
localization, and one such TF is Forkhead box O1 (FOXO1). FOXO1 integrates
antigen-binding, co-receptor activation and metabolic signals in lymphocytes,
leading to proliferation and differentiation. Importantly, the nuclear or
cytoplasmic localization of FOXO1 is key for gene expression leading to different
lymphocyte phenotypes. In effector lymphocytes (Teff), for example, lymphocyte
receptor (TCR) signaling leads to an Akt-dependent phosphorylation of FOXO1.
Phosphorylated FOXO1 is excluded from the nucleus, promoting proliferation and
effector functions. In contrast, nuclear retention of FOXO1 is essential for
early and late development of T and B cells and for the thymic development and
stability of regulatory T cells. Given the critical role of FOXO1 localization as
an indicator and determinant of function, quantification of FOXO1 cellular
localization in human lymphocytes can help determine immune cell activation and
activity in experimental and clinical scenarios. The standard method used to
determine subcellular protein localization is the analysis of nuclear and
cytoplasmic protein extracts by Western blotting (WB). However, available
techniques, such as WB, are limited by a requirement for a large number of cells
and inability to determine FOXO1 localization in individual cells or sub
populations. In contrast, a standardized method using an imaging flow cytometer
(IFC) such as the Amnis ImagestreamX Mark II, would provide both qualitative, per
cell localization information, as well as quantitative data on gated sub
populations. To this end, we report the development and optimization of an IFC
protocol to examine native FOXO1 localization in human lymphocytes. A human CD4+
lymphocyte line, HuT102, as well as primary human T cells, were assessed for
dynamic FOXO1 localization after treatment with a lymphocyte receptor signaling
mimic (PMA/Ionomycin). IFC nuclear translocation analysis permitted us to
precisely quantify the alterations over time in nuclear and cytoplasmic
localization of native FOXO1 on a per cell basis, including within specific, user
defined sub-populations of cells. For human lymphocytes, using IFC to assess and
quantify dynamic FOXO1 localization allows the user to simultaneously study
multiple lymphocyte subpopulations as well as to delineate differing effects of
dynamic FOXO1 localization that may be lost when other available methods are
used.
PMID- 29337048
TI - Pathologic Findings of Symptomatic Carotid Artery Stenosis Several Decades after
Radiation Therapy: A Case Report.
AB - Improved long-term survival of malignancy has drawn increased attention to late
cerebrovascular toxicity after neck radiotherapy. Recently, neck radiotherapy has
been found as a significant risk factor of carotid artery stenosis and ischemic
stroke; however, long-term adverse effects of radiation in large arteries remain
unknown. Here, we described an autopsied case with recurrent ischemic stroke
associated with ipsilateral carotid artery stenosis several decades after neck
radiation therapy. Pathologically, there were intima-media fibrosis, endothelial
cell loss, and decreased expression of thrombomodulin in irradiated carotid
artery stenosis. Our findings support the hypothesis that long-term radiation
induced vascular injury in large arteries is morphologically different from
atherosclerotic change. Furthermore, endothelial cell injury may promote fibrin
thrombus formation through decreased expression of thrombomodulin, which may
cause ischemic stroke associated with radiation-induced carotid artery stenosis.
PMID- 29337049
TI - Sphingosine-1-Phosphate Receptor 1 Activation Enhances Leptomeningeal Collateral
Development and Improves Outcome after Stroke in Mice.
AB - BACKGROUND: Development of collateral circulation after acute ischemic stroke is
triggered by shear stress that occurs in pre-existing arterioles. Recently,
sphingosine-1-phosphate receptor 1 (S1P1) on endothelial cells was reported to
sense shear stress and transduce its signaling pathways. METHODS: BALB/c mice (n
= 118) were subjected to permanent middle cerebral artery occlusion (pMCAO) or
sham operation. We investigated the effect of an S1P1-selective agonist SEW2871
on leptomeningeal collateral arteries and neurological outcome after pMCAO.
RESULTS: Immunohistochemistry showed that without treatment, the expression of
S1P1 on endothelial cells of leptomeningeal arteries and capillaries increased
early after pMCAO, peaking at 6 hours, whereas a significant increase in the
expression of S1P1 in neurons was seen from 24 hours later. After intraperitoneal
administration of SEW2871 for 7 days after pMCAO, the number of leptomeningeal
collateral arteries was significantly increased, cerebral blood flow improved,
infarct volume was decreased, and neurological outcome improved compared with the
controls. Significantly increased phosphorylation of endothelial nitric oxide
synthase (eNOS) as early as 6 hours after pMCAO and higher expression of tight
junction proteins at postoperative day 3 were observed with SEW2871 treatment as
assessed by Western blot. Daily administration of SEW2871 also increased
capillary density in peri-infarct regions and promoted monocyte/macrophage
mobilization to the surface of ischemic cortex at 7 days after pMCAO.
CONCLUSIONS: An S1P1-selective agonist enhanced leptomeningeal collateral
circulation via eNOS phosphorylation and promoted postischemic angiogenesis with
reinforced blood-brain barrier integrity in a mouse model of acute ischemic
stroke, leading to smaller infarct volume and better neurological outcome.
PMID- 29337050
TI - Impairments in social novelty recognition and spatial memory in mice with
conditional deletion of Scn1a in parvalbumin-expressing cells.
AB - Loss of function mutations in the SCN1A gene, which encodes the voltage-gated
sodium channel Nav1.1, have been described in the majority of Dravet syndrome
patients presenting with epileptic seizures, hyperactivity, autistic traits, and
cognitive decline. We previously reported predominant Nav1.1 expression in
parvalbumin-expressing (PV+) inhibitory neurons in juvenile mouse brain and
observed epileptic seizures in mice with selective deletion of Scn1a in PV+ cells
mediated by PV-Cre transgene expression (Scn1afl/+/PV-Cre-TG). Here we
investigate the behavior of Scn1afl/+/PV-Cre-TG mice using a comprehensive
battery of behavioral tests. We observed that Scn1afl/+/PV-Cre-TG mice display
hyperactive behavior, impaired social novelty recognition, and altered spatial
memory. We also generated Scn1afl/+/SST-Cre-KI mice with a selective Scn1a
deletion in somatostatin-expressing (SST+) inhibitory neurons using an SST-IRES
Cre knock-in driver line. We observed that Scn1afl/+/SST-Cre-KI mice display no
spontaneous convulsive seizures and that Scn1afl/+/SST-Cre-KI mice have a lowered
threshold temperature for hyperthermia-induced seizures, although their threshold
values are much higher than those of Scn1afl/+/PV-Cre-TG mice. We finally show
that Scn1afl/+/SST-Cre-KI mice exhibited no noticeable behavioral abnormalities.
These observations suggest that impaired Nav1.1 function in PV+ interneurons is
critically involved in the pathogenesis of hyperactivity, autistic traits, and
cognitive decline, as well as epileptic seizures, in Dravet syndrome.
PMID- 29337051
TI - FERMT2 links cortical actin structures, plasma membrane tension and focal
adhesion function to stabilize podocyte morphology.
AB - Simplification and retraction of podocyte protrusions, generally termed as foot
process effacement, is a uniform pathological pattern observed in the majority of
glomerular disease, including focal segmental glomerulosclerosis. However, it is
still incompletely understood how the interaction of cortical actin structures,
actomyosin contractility and focal adhesions, is being orchestrated to control
foot process morphology in health and disease. By uncovering the functional role
of fermitin family member 2 (FERMT2 or kindlin-2) in podocytes, we provide now
evidence, how cell-extracellular matrix (ECM) interactions modulate membrane
tension and actomyosin contractility. A genetic modeling approach was applied by
deleting FERMT2 in a set of in vivo systems as well as in CRISPR/Cas9 modified
human podocytes. Loss of FERMT2 results in altered cortical actin composition,
cell cortex destabilization associated with plasma membrane blebbing and a
remodeling of focal adhesions. We further show that FERMT2 knockout podocytes
have high levels of RhoA activation and concomitantly increased actomyosin
contractility. Inhibition of actomyosin tension reverses the membrane blebbing
phenotype. Thus, our findings establish a direct link between cell-matrix
adhesions, cortical actin structures and plasma membrane tension allowing to
better explain cell morphological changes in foot process effacement.
PMID- 29337052
TI - Sweet, yet underappreciated: Proteoglycans and extracellular matrix remodeling in
heart disease.
AB - Extracellular matrix remodeling is extensive in several heart diseases and
hampers cardiac filling, often leading to heart failure. Proteoglycans have over
the last two decades emerged as molecules with important roles in matrix
remodeling and fibrosis in the heart. Here we discuss and review current
literature on proteoglycans that have been studied in cardiac remodeling. The
small leucine rich proteoglycans (SLRPs) are located within the extracellular
matrix and are organizers of the matrix structure. Membrane-bound proteoglycans,
such as syndecans and glypicans, act as receptors and direct cardiac fibroblast
signaling. Recent studies indicate that proteoglycans are promising as diagnostic
biomarkers for cardiac fibrosis, and that they may provide new therapeutic
strategies for cardiac disease.
PMID- 29337053
TI - Oral ingestion of plasmalogens can attenuate the LPS-induced memory loss and
microglial activation.
AB - Plasmalogens (Pls) are the special phospholipids which were reported to be
reduced in brain and blood samples of Alzheimer's disease (AD) patients,
suggested a possibility that an oral ingestion of Pls may prevent the disease
progression. Interestingly, the clinical study showed that the daily oral
ingestion of Pls among the mild AD patients improved cognition. However, it is
unknown of whether the oral ingestion of Pls inhibits the AD like changes in
brain e.g., glial activation and accumulation of amyloid beta (Abeta) proteins.
To elucidate the beneficial effects of the Pls oral ingestion, we have used the
chronic lipopolysaccharide (LPS) injection model mice where the glial activation
and Abeta accumulation were well reported. In the present study, we have found
that the Pls drinking at the doses of 0.1 MUg/ml and 10 MUg/ml for 3 months
attenuated the glial activation and accumulation of amyloid beta (Abeta) proteins
in the murine brain. Interestingly, the LPS injection reduced the hippocampal
dependent memory in the control mice but the groups of Pls drinking mice showed a
better performance in the memory test, suggesting that oral intake of Pls can
inhibit LPS-mediated memory loss associated with a reduction of glial activation
and Abeta accumulation in the brain. We, therefore, suggest that the oral
ingestion of Pls among the AD patients may also inhibit the glial activation
resulting in the improvement of cognition.
PMID- 29337054
TI - Deficiency of primary cilia in kidney epithelial cells induces epithelial to
mesenchymal transition.
AB - Primary cilium is a microtubule-based non-motile organelle that plays critical
roles in kidney pathophysiology. Our previous studies revealed that the lengths
of primary cilia decreased upon renal ischemia/reperfusion injury and oxidative
stress, and restored with recovery. Here, we tested the hypothesis that lack of
primary cilium causes epithelial to mesenchymal transition (EMT) of kidney tubule
cells. We investigated the alteration of length of primary cilia in TGF-beta
induced EMT via visualization of primary cilia by fluorescence staining against
acetylated alpha-tubulin. EMT was determined by measuring mesenchymal protein
expression using quantitative PCR and indirect fluorescence staining. As a
result, TGF-beta treatment decreased ciliary length along with EMT. To test
whether defect of primary cilia trigger onset of EMT, cilia formation was
disturbed by knock down of ciliary protein using siRNA along with/without TGF
beta treatment. Knock down of Arl13b and Ift20 reduced cilia elongation and
increased expression of EMT markers such as fibronectin, alpha-SMA, and collagen
III. TGF-beta-induced EMT was greater as well in Arl13b and Ift20-knock down
cells compared to control cells. Taken together, deficiency of primary cilia
trigger EMT and exacerbates it under pro-fibrotic signals.
PMID- 29337055
TI - A novel circular RNA, hsa_circ_0046701, promotes carcinogenesis by increasing the
expression of miR-142-3p target ITGB8 in glioma.
AB - In the present study, we identified a novel circular RNA (circRNA),
hsa_circ_0046701, in glioma cells. We measured the expression of hsa_circ_0046701
using qRT-PCR in glioma tissues and cell lines, and explored its functions using
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation,
and Transwell assays. Luciferase reporter assays were performed to validate the
correlation between microRNA miR-142-3p and hsa_circ_0046701 or integrin subunit
beta 8 (ITGB8). The results showed that hsa_circ_0046701 was significantly
upregulated in glioma tissues and cell lines, and knockdown of hsa_circ_0046701
inhibited cell proliferation and invasion. Luciferase reporter assays indicated
that hsa_circ_0046701 functions as a sponge for miR-142-3p and regulates the
expression of ITGB8. Subsequently, functional assays revealed that silencing of
hsa_circ_0046701 could upregulate miR-142-3p, resulting in downregulation of
ITGB8. The results demonstrated that the hsa_circ_0046701/miR-142-3p/ITGB8 axis
might play critical regulatory roles in the pathogenesis and development of
glioma.
PMID- 29337056
TI - Comparison of EMT mediated tyrosine kinase inhibitor resistance in NSCLC.
AB - In the United States, lung cancer is the second most common cancer in men and
women. In 2017, 222,500 new cases and 155,870 deaths from lung cancer are
estimated to have occurred. A tyrosine kinase receptor, epidermal growth factor
receptor (EGFR), is over expressed or mutated in non-small cell lung cancer
(NSCLC) resulting in increased cell proliferation and survival. Tyrosine kinase
inhibitors (TKIs) are currently being used as therapy for NSCLC patients,
however, they have limited efficacy in NSCLC patients due to acquisition of
resistance. This study investigates the role of epithelial-mesenchymal transition
(EMT) in the development of resistance against TKIs in NSCLC. Currently, the role
of p120-catenin, Kaiso factor and PRMT-1 in reversal of EMT in T790M mutated and
TKI-resistant NSCLC cells is a new line of study. In this investigation we found
upregulation of cytoplasmic p120-catenin, which was co-localized with Kaiso
factor. In the nucleus, binding of p120-catenin to Kaiso factor initiates
transcription by activating EMT-transcription factors such as Snail, Slug, Twist,
and ZEB1. PRMT-1 was also found to be upregulated, which induces methylation of
Twist and repression of E-cadherin activity, thus promoting EMT. We confirmed
that TKI-resistant cells have mesenchymal cell type characteristics based on
their cell morphology and gene or protein expression of EMT related proteins. EMT
proteins, Vimentin and N-cadherin, displayed increased expression, whereas E
cadherin expression was downregulated. Finally, we found that the knockdown of
p120-catenin and PRMT-1 by siRNA or use of a PRMT-1 inhibitor Furamidine
increased Erlotinib sensitivity and could reverse EMT to overcome TKI resistance.
PMID- 29337057
TI - Heterogeneity of autophagic status in pancreatic beta cells under metabolic
stress.
AB - Autophagy in beta cells has been demonstrated to play a pivotal role in cellular
homeostasis and the progression of glucose intolerance. Although autophagic
activity is affected by metabolic stress both in vivo and in vitro, it remains
unclear as to what extent the autophagic status in each beta cell is different
from its neighboring cells. To address this question, GFP-LC3 reporter mice,
which can visualize the autophagic status of each beta cell as green-fluorescent
puncta, were crossed with obese diabetic db/db mice. Imaging of green-fluorescent
puncta in the islets of GFP-LC3 mice revealed that beta cells are a heterogeneous
population, as the density of GFP-LC3 puncta in each cell was variable.
Furthermore, the variability was greater in GFP-LC3; db/db mice than in non
diabetic GFP-LC3; db/+ mice. Furthermore, when GFP-LC3 mice were treated with a
low dose of S961, which antagonizes insulin signaling without inducing overt
hyperglycemia, the number of beta cells with a high density of GFP puncta was
increased, suggesting that insulin resistance affects autophagic status
independently of glucose profiles. These results suggest that pancreatic beta
cells under metabolic stress are heterogeneous regarding their autophagic status,
which provides insights into the cellular dynamics of each beta cell rather than
the whole beta-cell population.
PMID- 29337058
TI - EHMT2 is a metastasis regulator in breast cancer.
AB - Various modes of epigenetic regulation of breast cancer proliferation and
metastasis have been investigated, but epigenetic mechanisms involved in breast
cancer metastasis remain elusive. Thus, in this study, EHMT2 (a histone
methyltransferase) was determined to be significantly overexpressed in breast
cancer tissues and in Oncomine data. In addition, knockdown of EHMT2 reduced cell
migration/invasion and regulated the expression of EMT-related markers (E
cadherin, Claudin 1, and Vimentin). Furthermore, treatment with BIX-01294, a
specific inhibitor of EHMT2, affected migration/invasion in MDA-MB-231 cells.
Therefore, our findings demonstrate functions of EHMT2 in breast cancer
metastasis and suggest that targeting EHMT2 may be an effective therapeutic
strategy for preventing breast cancer metastasis.
PMID- 29337059
TI - FPPS mediates TGF-beta1-induced non-small cell lung cancer cell invasion and the
EMT process via the RhoA/Rock1 pathway.
AB - Farnesyl pyrophosphate synthase (FPPS), a key enzyme in the mevalonate pathway,
was recently shown to play a role in cancer progression. However, its role in non
small cell lung cancer (NSCLC) metastasis and the underlying mechanism remain
unclear. In this study, FPPS expression was significantly correlated with TNM
stage, and metastasis. Inhibition or knockdown of FPPS blocked TGF-beta1-induced
cell invasion and epithelial-to-mesenchymal transition (EMT) process. FPPS
expression of FPPS was induced by TGF-beta1 and FPPS promoted cell invasion and
EMT via the RhoA/Rock1 pathway. In conclusion, FPPS mediates TGF-beta1-induced
lung cancer cell invasion and EMT via the RhoA/Rock1 pathway. These findings
suggest new treatment strategies to reduce mortality associated with metastasis
in patients with NSCLC.
PMID- 29337060
TI - Amelogenin X impacts age-dependent increase of frequency and number in labial
incisor grooves in C57BL/6.
AB - Labial grooves in maxillary incisors have been reported in several wild-type
rodent species. Previous studies have reported age-dependent labial grooves occur
in moderate prevalence in C57BL/6 mice; however, very little is known about the
occurrence of such grooves. In the present study, we observed age-dependent
groove formation in C57BL/6 mice up to 26 months after birth and found that not
only the frequency of the appearance of incisor grooves but also the number of
grooves increased in an age-dependent manner. We examined the molecular
mechanisms of age-dependent groove formation by performing DNA microarray
analysis of the incisors of 12-month-old (12M) and 24-month-old (24M) mice.
Amelx, encoding the major enamel matrix protein AMELOGENIN, was identified as a
12M-specific gene. Comparing with wild-type mice, the maxillary incisors of Amelx
/- mutants indicated the increase of the frequency and number of labial grooves.
These findings suggested that the Amelx gene impacts the age-dependent appearance
of the labial incisor groove in C57BL/6 mice.
PMID- 29337061
TI - Metabolic reprogramming in keloid fibroblasts: Aerobic glycolysis and a novel
therapeutic strategy.
AB - Keloids, tumor-like fibroproliferative cutaneous lesions, were reported in
metabolic disturbance. However, the metabolic character remains unclear. The
purpose of this study is to determine if glycolytic reprogramming is important
for the pathogenesis of keloids and to assess the inhibition potential of
glycolysis in keloid treatment. An intracellular metabolic profile assay was used
to compare metabolic phenotypes between normal skin fibroblasts and keloid
fibroblasts (NFs and KFs). Our data indicated that KFs underwent reprogramming of
their metabolic phonotype from oxidative phosphorylation to aerobic glycolysis
(Warburg effect) with augmented glycolysis and glycolytic capacity. Both gene and
protein assays showed that the expression of glycolytic enzymes was upregulated
in KFs compared to NFs. Our data showed higher glucose influx and lactate
production in KFs compared to NFs. Furthermore, the proliferation of KFs was
suppressed in a dose-dependent and time-dependent manner after inhibition of
glycolysis with 2-deoxy-glucose (2-DG). Taken together, these findings suggested
that keloids underwent a reprogrammed metabolic phenotype of aerobic glycolysis.
This was essential for keloid hyperplasia, and glycolytic inhibitors might
provide a potential treatment for keloids.
PMID- 29337062
TI - Anti-inflammatory and proresolution activities of bergapten isolated from the
roots of Ficus hirta in an in vivo zebrafish model.
AB - Bergapten (5-methoxypsoralen), a coumarin-derivate compound isolated from Ficus
hirta roots, was evaluated for its anti-inflammatory and proresolution activities
in a tail-cutting-induced zebrafish larvae model. Bergapten was evaluated using a
caudal fin-wounded transgenic zebrafish line "Tg(corola: eGFP)" to visualize the
effects of the recruitment and clearance of neutrophils and macrophages at the
injury site. We found that bergapten significantly suppressed the recruitment of
neutrophils and macrophages toward the injury site, as well as promoted the
clearance of neutrophils and macrophages from the wound site. We also
investigated the reactive oxygen species (ROS) and nitric oxide (NO) level of
bergapten in a tail-cutting-induced inflammation zebrafish model. The Results
revealed that bergapten effectively inhibited the tail-cutting-induced production
of ROS and NO in zebrafish larvae. This study reported for the first time the
potential anti-inflammatory and proresolution activities of bergapten in an in
vivo zebrafish model, suggesting that bergapten may be a potential candidate for
inflammation therapy.
PMID- 29337063
TI - BMI1 activates WNT signaling in colon cancer by negatively regulating the WNT
antagonist IDAX.
AB - Aberrant activation of Wnt signaling plays a critical role in the development of
colon cancer. BMI, a component of the polycomb repressive complex (PRC1), is
upregulated in various types of cancer and contributes to epigenetic silencing of
tumor suppressors. In this study, we showed that BMI1 is upregulated in colon
cancer tissues and cell lines. Overexpression of BMI1 in primary epithelial colon
cells promotes cellular growth and activates WNT pathway, while BMI1 silencing in
colon cancer cells represses these effects. We also found that BMI1 binds to the
promoter of IDAX, a Wnt antagonist, and decreases its transcription. Expression
of IDAX is downregulated in colon cancer tissues and cell lines and negatively
correlated with BMI1 in colon cancer tissues. Furthermore, Silencing of IDAX
counteracts the effects of BMI1 suppression, while its overexpression reverses
oncogenic effects of BMI1. Together, these findings indicate that BMI1-mediated
IDAX epigenetic suppression is crucial for enhancement of colon carcinogenesis,
suggesting that BMI1?IDAX axis as a potential novel diagnostic and therapeutic
target of colon cancer.
PMID- 29337064
TI - Cloning and functional characterization of a p-coumaroyl quinate/shikimate 3'
hydroxylase from potato (Solanum tuberosum).
AB - Chlorogenic acid (CGA) plays an important role in protecting plants against
pathogens and promoting human health. Although CGA accumulates to high levels in
potato tubers, the key enzyme p-coumaroyl quinate/shikimate 3'-hydroxylase (C3'H)
for CGA biosynthesis has not been isolated and functionally characterized in
potato. In this work, we cloned StC3'H from potato and showed that it catalyzed
the formation of caffeoylshikimate and CGA (caffeoylquinate) from p-coumaroyl
shikimate and p-coumaroyl quinate, respectively, but was inactive towards p
coumaric acid in in vitro enzyme assays. When the expression of StC3'H proteins
was blocked through antisense (AS) inhibition under the control of a tuber
specific patatin promoter, moderate changes in tuber yield as well as phenolic
metabolites in the core tuber tissue were observed for several AS lines. On the
other hand, the AS and control potato lines exhibited similar responses to a
bacterial pathogen Pectobacterium carotovorum. These results suggest that StC3'H
is implicated in phenolic metabolism in potato. They also suggest that CGA
accumulation in the core tissue of potato tubers is an intricately controlled
process and that additional C3'H activity may also be involved in CGA
biosynthesis in potato.
PMID- 29337065
TI - Downregulated circular RNA hsa_circ_0001649 regulates proliferation, migration
and invasion in cholangiocarcinoma cells.
AB - Cholangiocarcinoma (CCA) is one of the most aggressive malignancies with
increasing worldwide incidence and is characterized by unfavorable prognosis due
to its early invasive characteristics and poor response to chemotherapy or
radiotherapy. Accumulating evidence has indicated that aberrantly expressed
circular RNAs (circRNAs) are involved in cancer development and progression.
However, their clinical values and biological roles in CCA remain unclear.
Hsa_circ_0001649, a novel cancer-related circRNA, has been previously reported to
be downregulated in hepatocellular carcinoma and gastric cancer. In the present
study, qRT-PCR was carried out to measure the expression of hsa_circ_0001649 in
CCA tissue samples and cell lines, and the correlation between hsa_circ_0001649
expression and clinicopathologic features was analyzed. The biological functions
of hsa_circ_0001649 in CCA cells were evaluated both in vitro and in vivo. As a
result, hsa_circ_0001649 was aberrantly downregulated in CCA tissues and cells,
and this downregulation was associated with tumor size and differentiation grade
in CCA. In addition, hsa_circ_0001649 overexpression caused tumor suppressive
effects via inhibiting cell proliferation, migration and invasion; inducing cell
apoptosis in KMBC and Huh-28 cells. On the contrary, silencing of
hsa_circ_0001649 caused the opposite phenotypes. Furthermore, tumor xenograft
study confirmed the in vitro results. Collectively, our findings suggest that
hsa_circ_0001649 might be a rational CCA-related therapeutic target.
PMID- 29337066
TI - Listeria monocytogenes endocarditis: case report, review of the literature, and
laboratory evaluation of potential novel antibiotic synergies.
AB - Endocarditis is a rare but serious manifestation of Listeria monocytogenes (LM).
However, the optimal treatment strategy for LM endocarditis has yet to be
established. Current antibiotic strategies for listeriosis include penicillin G
or ampicillin (AMP) monotherapy, or AMP + gentamicin combination therapy which is
often favored for endocarditis. The primary objective of our investigation was to
assess the utility of AMP + ceftriaxone (CRO) and AMP + daptomycin (DAP) against
LM, modeling less nephrotoxic antibiotic combinations traditionally used to
manage resistant enterococcal endocarditis. Here we report a case of LM
endocarditis, review the world literature, and evaluate alternative treatment
strategies for listeriosis utilizing in vitro and ex vivo studies. The
combination of AMP + CRO and AMP + DAP were each noted to have synergistic
activity against a LM endocarditis isolate. Additionally, co-incubation of the
isolate with sub-lethal concentrations of antibiotics (AMP, CRO, DAP, AMP + CRO
or AMP + DAP) sensitized the bacterium to whole blood killing while pretreatment
with CRO and DAP (at 1/4 MIC) sensitized the bacterium to neutrophil killing.
However, these effects did not reflect potentiation of antibiotic activity to
human cathelicidin peptide LL-37, which is abundant in neutrophils and highly
active against LM. Interestingly, AMP pretreatment of the LM endocarditis isolate
resulted in increased DAP binding to the bacterium when assessed by fluorescence
microscopy. These in vitro and ex vivo studies suggest further investigation of
combination therapy using AMP + CRO or AMP + DAP as an alternative treatment for
LM infection is warranted.
PMID- 29337067
TI - The impact of growth factors on human induced pluripotent stem cells
differentiation into cardiomyocytes.
AB - : Human induced pluripotent stem cells (hiPSCs) act as a promising therapeutic
alternative for cardiovascular diseases. They yield a large number of functional
cardiomyocytes (CMs) from autologous cell sources without ethical or
immunological problems. However, significant limitations still remain in terms of
line-to-line variability in CM yield and reproducibility. AIM: To efficiently
enhance NP0040 hiPSCs differentiation into CMs. MAIN METHODS: Following a
standard cardiac differentiation protocol using small molecules targeting the
canonical Wnt signaling, growth factors (BMP4 and FGF2) and ascorbic acid were
added further in order to increase the cardiac differentiation efficiency. All
cultures were conducted in serum-free, feeder-free monolayer system followed by
lactate purification. KEY FINDINGS: Using NP0040 hiPSCs, the CM yield resulting
from modulation of the Wnt signaling pathway alone was inefficient compared to
previous studies while the addition of BMP4, FGF2 and ascorbic acid resulted in
enhanced cardiac differentiation outcome. The later resulted in a high yield (up
to 92%) of cardiac troponin-T (cTnT) + CMs contracting spontaneously as organized
sheets in 15 independent experiments. They were validated structurally and
functionally using immunofluorescent staining for sarcomeric alpha-actinin, cTnT,
MLC2v and Connexin 43. Reverse-transcriptase PCR revealed cardiac transcription
factors and cardiac-specific genes expression. CMs were electrically connected to
one another. Recorded action potential (AP) showed waves of relatively mature
ventricular-like phenotype. SIGNIFICANCE: We demonstrated that hiPSC lines
respond differently to a standard cardiac differentiation protocol and that a
well-orchestrated interplay between Wnt, BMP4, FGF/MEK and Ascorbic acid
MEK/ERK1/2 signaling pathways is beneficial in enhancing the differentiation
outcome.
PMID- 29337068
TI - The impact of compression force and pressure at prevalent screening on subsequent
re-attendance in a national screening program.
AB - Adherence to screening may indirectly help assess whether a prior screening
examination deters women from returning for a subsequent examination. We
investigated whether compression force and pressure in mammography were
associated with re-attendance among prevalently screened women in the organized
breast cancer screening program in Norway. Data on compression force (kg) and
pressure (kPa) from women's first screening examination in the program (prevalent
screening) and subsequent re-attendance were available for 31,225 women aged 50
68, screened during 2007-2013. Crude re-attendance rates and log-binomial
regression models estimating the prevalence ratio of re-attendance were used to
identify the association between compression force or pressure and re-attendance
two-years later. Age and year at prevalent screening, county of residence,
screening result (negative or false positive), breast volume, and breast density
were included in analyses. Overall, 27,197 (87.1%) women re-attended the program.
Re-attendance was highest for women who received a compression force of 10.0-13.9
kg (87.5%) or pressure of 9.0-17.9 kPa (87.8%) and lowest for those who received
a compression force of <10.0 kg (85.0%) or pressure of <9.0 kPa (84.7%). The
adjusted prevalence of re-attendance was 3% lower for women who received low
compression force (<10.0 kg) and 2% lower for women who received low compression
pressure (<9.0 kPa) relative to the reference groups (10.0-13.9 kg and 9.0-17.9
kPa, respectively). Future research related to re-attendance should also include
information about women's experience of pain, anxiety and stress, as well as
image quality.
PMID- 29337069
TI - A survey instrument for measuring vaccine acceptance.
AB - Accurately measuring vaccine acceptance is important, especially under current
conditions in which misinformation may increase public anxiety about vaccines and
politicize vaccination policies. We integrated substantive knowledge,
conceptualization and measurement expertise, and survey design principles to
develop an instrument for measuring vaccine acceptance across the general public.
Given this broad goal, we expect our novel instrument will complement, rather
than replace, existing instruments designed specifically to measure parents'
vaccine hesitancy. Our instrument measures five key facets of vaccine acceptance:
(1) perceived safety of vaccines; (2) perceived effectiveness and necessity of
vaccines; (3) acceptance of the selection and scheduling of vaccines; (4)
positive values and affect toward vaccines; and (5) perceived legitimacy of
authorities to require vaccinations. We report results of analyses demonstrating
the reliability and validity of this instrument. High Cronbach's alpha values for
five sub-scales and for the full scale indicate the instrument's reliability, and
the consistent performance of expected predictors (i.e., trust in biologists,
conspiratorial ideation, and political ideology) demonstrates the instrument's
construct validity. Further, scientific reasoning increases vaccine acceptance
among liberals but decreases vaccine acceptance among conservatives, which is
consistent with motivated cognition. Also, trust in biologists has a stronger
positive effect on vaccine acceptance among conservatives than among liberals,
signaling a potentially promising means to reduce political polarization on
vaccines and increase vaccine acceptance across the general public. We end by
identifying key ways that public health researchers, science studies scholars,
and health practitioners may employ the full (or short) version of our vaccine
acceptance instrument.
PMID- 29337070
TI - Intrinsic and extrinsic contributors to defective CD8+ T cell responses with
aging.
AB - Aging has a profound effect on the immune system, and both innate and adaptive
arms of the immune system show functional decline with age. In response to
infection with intracellular microorganisms, old animals mobilize decreased
numbers of antigen-specific CD8+ T cells with reduced production of effector
molecules and impaired cytolytic activity. However, the CD8+ T cell-intrinsic
contribution to, and molecular mechanisms behind, these defects remain unclear.
In this review we will discuss the mechanistic contributions of age related
changes in the CD8+ T cell pool and the relative roles of intrinsic functional
defects in aged CD8+ T cells vs. defects in the aged environment initiating the
CD8+ T cell response.
PMID- 29337071
TI - Lower protein and higher carbohydrate intake are related with altering metabolic
syndrome components in elderly women: A cross-sectional study.
AB - BACKGROUND: Metabolic Syndrome (MetS) is an energy-disturbance disease associated
with insulin resistance. Hence, the intake of energy-rich macronutrients might
affect some MetS components. The aim of this study was to explore the association
of ingested macronutrients with MetS components in older women. METHODS: A cross
sectional study was conducted in 245 older women (>=60 years). Whole-body dual
energy X-ray absorptiometry was used to assess total body fat, percentage body
fat (absolute and relative), and skeletal muscle mass. Venous blood samples were
collected after a 12 h fasting to determine glucose, high-density lipoprotein
(HDL-c), and triglycerides. Anthropometric measurements and resting blood
pressure were also evaluated. Food consumption was assessed through the 24-hour
dietary recall method, and the macronutrients were distributed by tertiles of
consumption. The Student t-test, Mann-Whitney U test, and logistic regression
analysis were used for statistical analysis. RESULTS: The MetS and non-MetS
groups demonstrated similar food-energy intake and fat consumption. The MetS
group presented lower protein and higher carbohydrate intake than the non-MetS
group. Individuals in the lowest protein intake (<0.72 g/kg/d) had greater odds
of presenting abdominal obesity and impaired glucose levels. Higher consumption
of carbohydrates was associated with lower HDL levels and higher
hypertriglyceridemia. The chances of having MetS were increased by three times
when ingesting either a low protein or high carbohydrate diet. CONCLUSION: Either
high carbohydrate or low protein intake would be risk factors for altering MetS
components and the presence of MetS in elderly women.
PMID- 29337072
TI - Valorization of Brewer's spent grain to prebiotic oligosaccharide: Production,
xylanase catalyzed hydrolysis, in-vitro evaluation with probiotic strains and in
a batch human fecal fermentation model.
AB - Brewer's spent grain (BSG) accounts for around 85% of the solid by-products from
beer production. BSG was first extracted to obtain water-soluble arabinoxylan
(AX). Using subsequent alkali extraction (0.5 M KOH) it was possible to dissolve
additional AX. In total, about 57% of the AX in BSG was extracted with the purity
of 45-55%. After comparison of nine xylanases, Pentopan mono BG, a GH11 enzyme,
was selected for hydrolysis of the extracts to oligosaccharides with minimal
formation of monosaccharides. Growth of Bifidobacterium adolescentis (ATCC 15703)
was promoted by the enzymatic hydrolysis to arabinoxylooligosaccharides, while
Lactobacillus brevis (DSMZ 1264) utilized only unsubstituted
xylooligosaccharides. Furthermore, utilization of the hydrolysates by human gut
microbiota was also assessed in a batch human fecal fermentation model. Results
revealed that the rates of fermentation of the BSG hydrolysates by human gut
microbiota were similar to that of commercial prebiotic fructooligosaccharides,
while inulin was fermented at a slower rate. In summary, a sustainable process to
valorize BSG to functional food ingredients has been proposed.
PMID- 29337073
TI - Neofunctionalization of Duplicated P450 Genes Drives the Evolution of Insecticide
Resistance in the Brown Planthopper.
AB - Gene duplication is a major source of genetic variation that has been shown to
underpin the evolution of a wide range of adaptive traits [1, 2]. For example,
duplication or amplification of genes encoding detoxification enzymes has been
shown to play an important role in the evolution of insecticide resistance [3-5].
In this context, gene duplication performs an adaptive function as a result of
its effects on gene dosage and not as a source of functional novelty [3, 6-8].
Here, we show that duplication and neofunctionalization of a cytochrome P450,
CYP6ER1, led to the evolution of insecticide resistance in the brown planthopper.
Considerable genetic variation was observed in the coding sequence of CYP6ER1 in
populations of brown planthopper collected from across Asia, but just two
sequence variants are highly overexpressed in resistant strains and metabolize
imidacloprid. Both variants are characterized by profound amino-acid alterations
in substrate recognition sites, and the introduction of these mutations into a
susceptible P450 sequence is sufficient to confer resistance. CYP6ER1 is
duplicated in resistant strains with individuals carrying paralogs with and
without the gain-of-function mutations. Despite numerical parity in the genome,
the susceptible and mutant copies exhibit marked asymmetry in their expression
with the resistant paralogs overexpressed. In the primary resistance-conferring
CYP6ER1 variant, this results from an extended region of novel sequence upstream
of the gene that provides enhanced expression. Our findings illustrate the
versatility of gene duplication in providing opportunities for functional and
regulatory innovation during the evolution of an adaptive trait.
PMID- 29337074
TI - In Situ Clock Shift Reveals that the Sun Compass Contributes to Orientation in a
Pelagic Seabird.
AB - Compass orientation is central to the control of animal movement from the scale
of local food-caching movements around a familiar area in parids [1] and corvids
[2, 3] to the first autumn vector navigation of songbirds embarking on long
distance migration [4-6]. In the study of diurnal birds, where the homing pigeon,
Columba livia, has been the main model, a time-compensated sun compass [7] is
central to the two-step map-and-compass process of navigation from unfamiliar
places, as well as guiding movement via a representation of familiar area
landmarks [8-12]. However, its use by an actively navigating wild bird is yet to
be shown. By phase shifting an animal's endogenous clock, known as clock-shifting
[13-15], sun-compass use can be demonstrated when the animal incorrectly consults
the sun's azimuthal position while homing after experimental displacement [15
17]. By applying clock-shift techniques at the nest of a wild bird during natural
incubation, we show here that an oceanic navigator-the Manx shearwater, Puffinus
puffinus-incorporates information from a time-compensated sun compass during
homeward guidance to the breeding colony after displacement. Consistently with
homing pigeons navigating within their familiar area [8, 9, 11, 18], we find that
the effect of clock shift, while statistically robust, is partial in nature,
possibly indicating the incorporation of guidance from landmarks into movement
decisions.
PMID- 29337075
TI - Brassinosteroids Dominate Hormonal Regulation of Plant Thermomorphogenesis via
BZR1.
AB - Thermomorphogenesis is defined as the suite of morphological changes that
together are likely to contribute to adaptive growth acclimation to usually
elevated ambient temperature [1, 2]. While many details of warmth-induced signal
transduction are still elusive, parallels to light signaling recently became
obvious (reviewed in [3]). It involves photoreceptors that can also sense changes
in ambient temperature [3-5] and act, for example, by repressing protein activity
of the central integrator of temperature information PHYTOCHROME-INTERACTING
FACTOR 4 (PIF4 [6]). In addition, PIF4 transcript accumulation is tightly
controlled by the evening complex member EARLY FLOWERING 3 [7, 8]. According to
the current understanding, PIF4 activates growth-promoting genes directly but
also via inducing auxin biosynthesis and signaling, resulting in cell elongation.
Based on a mutagenesis screen in the model plant Arabidopsis thaliana for mutants
with defects in temperature-induced hypocotyl elongation, we show here that both
PIF4 and auxin function depend on brassinosteroids. Genetic and pharmacological
analyses place brassinosteroids downstream of PIF4 and auxin. We found that
brassinosteroids act via the transcription factor BRASSINAZOLE RESISTANT 1
(BZR1), which accumulates in the nucleus at high temperature, where it induces
expression of growth-promoting genes. Furthermore, we show that at elevated
temperature BZR1 binds to the promoter of PIF4, inducing its expression. These
findings suggest that BZR1 functions in an amplifying feedforward loop involved
in PIF4 activation. Although numerous negative regulators of PIF4 have been
described, we identify BZR1 here as a true temperature-dependent positive
regulator of PIF4, acting as a major growth coordinator.
PMID- 29337077
TI - Chimeric Synergy in Natural Social Groups of a Cooperative Microbe.
AB - Many cooperative species form internally diverse social groups in which
individual fitness depends significantly on group-level productivity from
cooperation [1-4]. For such species, selection is expected to often disfavor
within-group diversity that reduces cooperative productivity [5, 6]. While
diversity within social groups is known to enhance productivity in some animals
[7-9], diversity within natural groups of social microbes is largely unexamined
in this regard. Cells of the soil bacterium Myxococcus xanthus respond to
starvation by constructing multicellular fruiting bodies within each of which a
subpopulation of cells transforms into stress-resistant spores [10]. Fruiting
bodies isolated from soil often harbor substantial endemic diversity [11] that
is, nonetheless, lower than between-group diversity, which increases with
distance from millimeter to global scales [12-14]. We show that M. xanthus clones
isolated from the same fruiting body often collectively produce more viable
spores in chimeric groups than expected from sporulation in genetically
homogeneous groups. In contrast, chimerism among clones derived from different
fruiting bodies tends to reduce group productivity, and it does so increasingly
as a function of spatial distance between fruiting-body sample sites. For one
fruiting body examined in detail, chimeric synergy-a positive quantitative effect
of chimerism on group productivity-is distributed broadly across an interaction
network rather than limited to a few interactions. We propose that these results
strengthen the plausibility of the hypothesis that selection may operate not only
within Myxococcus groups, but also between kin groups to disfavor within-group
variation that reduces productivity while allowing some forms of diversity that
generate chimeric synergy to persist.
PMID- 29337076
TI - Opposing Kinesin and Myosin-I Motors Drive Membrane Deformation and Tubulation
along Engineered Cytoskeletal Networks.
AB - Microtubule and actin filament molecular motors such as kinesin-1 and myosin-Ic
(Myo1c) transport and remodel membrane-bound vesicles; however, it is unclear how
they coordinate to accomplish these tasks. We introduced kinesin-1- and Myo1c
bound giant unilamellar vesicles (GUVs) into a micropatterned in vitro
cytoskeletal matrix modeled after the subcellular architecture where vesicular
sorting and membrane remodeling are observed. This array was composed of sparse
microtubules intersecting regions dense with actin filaments, and revealed that
Myo1c-dependent tethering of GUVs enabled kinesin-1-driven membrane deformation
and tubulation. Membrane remodeling at actin/microtubule intersections was
modulated by lipid composition and the addition of the Bin-Amphiphysin-Rvs-domain
(BAR-domain) proteins endophilin or FCH-domain-only (FCHo). Myo1c not only
tethered microtubule-transported cargo, but also transported, deformed, and
tubulated GUVs along actin filaments in a lipid-composition- and BAR-protein
responsive manner. These results suggest a mechanism for actin-based involvement
in vesicular transport and remodeling of intracellular membranes, and implicate
lipid composition as a key factor in determining whether vesicles will undergo
transport, deformation, or tubulation driven by opposing actin and microtubule
motors and BAR-domain proteins.
PMID- 29337078
TI - Circadian Waves of Transcriptional Repression Shape PIF-Regulated Photoperiod
Responsive Growth in Arabidopsis.
AB - Plants coordinate their growth and development with the environment through
integration of circadian clock and photosensory pathways. In Arabidopsis
thaliana, rhythmic hypocotyl elongation in short days (SD) is enhanced at dawn by
the basic-helix-loop-helix (bHLH) transcription factors PHYTOCHROME-INTERACTING
FACTORS (PIFs) directly inducing expression of growth-related genes [1-6]. PIFs
accumulate progressively during the night and are targeted for degradation by
active phytochromes in the light, when growth is reduced. Although PIF proteins
are also detected during the day hours [7-10], their growth-promoting activity is
inhibited through unknown mechanisms. Recently, the core clock components and
transcriptional repressors PSEUDO-RESPONSE REGULATORS PRR9/7/5 [11, 12], negative
regulators of hypocotyl elongation [13, 14], were described to associate to G
boxes [15], the DNA motifs recognized by the PIFs [16, 17], suggesting that PRR
and PIF function might converge antagonistically to regulate growth. Here we
report that PRR9/7/5 and PIFs physically interact and bind to the same promoter
region of pre-dawn-phased, growth-related genes, and we identify the
transcription factor CDF5 [18, 19] as target of this interplay. In SD, CDF5
expression is sequentially repressed from morning to dusk by PRRs and induced pre
dawn by PIFs. Consequently, CDF5 accumulates specifically at dawn, when it
induces cell elongation. Our findings provide a framework for recent TIMING OF
CAB EXPRESSION 1 (TOC1/PRR1) data [5, 20] and reveal that the long described
circadian morning-to-midnight waves of the PRR transcriptional repressors (PRR9,
PRR7, PRR5, and TOC1) [21] jointly gate PIF activity to dawn to prevent
overgrowth through sequential regulation of common PIF-PRR target genes such as
CDF5.
PMID- 29337079
TI - Rising pCO2 in Freshwater Ecosystems Has the Potential to Negatively Affect
Predator-Induced Defenses in Daphnia.
AB - Anthropogenically released CO2 accumulates in the global carbon cycle and is
anticipated to imbalance global carbon fluxes [1]. For example, increased
atmospheric CO2 induces a net air-to-sea flux where the oceans take up large
amounts of atmospheric CO2 (i.e., ocean acidification [2-5]). Research on ocean
acidification is ongoing, and studies have demonstrated the consequences for
ecosystems and organismal biology with major impacts on marine food webs,
nutrient cycles, overall productivity, and biodiversity [6-9]. Yet, surprisingly
little is known about the impact of anthropogenically caused CO2 on freshwater
systems due to their more complex biogeochemistry. The current consensus, yet
lacking data evidence, is that anthropogenic CO2 does indeed affect freshwater
carbon hydrogeochemistry, causing increased pCO2 in freshwater bodies [10-13]. We
analyzed long-term data from four freshwater reservoirs and observed a continuous
pCO2 increase associated with a decrease in pH, indicating that not only the
oceans but also inland waters are accumulating CO2. We tested the effect of pCO2
dependent freshwater acidification using the cosmopolite crustacean Daphnia. For
general validity, control pCO2-levels were based on the present global pCO2
average. Treatments were selected with very high pCO2 levels, assuming a
continuous non-linear increase of pCO2, reflecting worst-case-scenario future
pCO2 levels. Such levels of elevated pCO2 reduced the ability of Daphnia to sense
its predators and form adequate inducible defenses. We furthermore determined
that pCO2 and not the resulting reduction in pH impairs predator perception. If
pCO2 alters chemical communication between freshwater species, this perturbs
intra- and interspecific information transfer, which may affect all trophic
levels.
PMID- 29337080
TI - SMC1alpha Substitutes for Many Meiotic Functions of SMC1beta but Cannot Protect
Telomeres from Damage.
AB - The cohesin complex is built upon the SMC1/SMC3 heterodimer, and mammalian
meiocytes feature two variants of SMC1 named SMC1alpha and SMC1beta. It is
unclear why these two SMC1 variants have evolved. To determine unique versus
redundant functions of SMC1beta, we asked which of the known functions of
SMC1beta can be fulfilled by SMC1alpha. Smc1alpha was expressed under control of
the Smc1beta promoter in either wild-type or SMC1beta-deficient mice. No effect
was seen in the former. However, several major phenotypes of SMC1beta-deficient
spermatocytes were rescued by SMC1alpha. We observed extended development before
apoptosis and restoration of axial element and synaptonemal complex lengths,
chromosome synapsis, sex body formation, processing of DNA double-strand breaks,
and formation of MLH1 recombination foci. This supports the concept that the
quantity rather than the specific quality of cohesin complexes is decisive for
meiotic chromosome architecture. It also suggests plasticity in complex
composition, because to replace SMC1beta in many functions, SMC1alpha has to more
extensively associate with other cohesins. The cells did not complete meiosis but
died to the latest at the pachytene-to-diplotene transition. Telomere aberrations
known from Smc1beta-/- mice persisted, and DNA damage response and repair
proteins accumulated there regardless of expression of SMC1alpha. Thus, whereas
SMC1alpha can substitute for SMC1beta in many functions, the protection of
telomere integrity requires SMC1beta.
PMID- 29337081
TI - Abolishment of Spontaneous Flight Turns in Visually Responsive Drosophila.
AB - Animals react rapidly to external stimuli, such as an approaching predator, but
in other circumstances, they seem to act spontaneously, without any obvious
external trigger. How do the neural processes mediating the execution of
reflexive and spontaneous actions differ? We studied this question in tethered,
flying Drosophila. We found that silencing a large but genetically defined set of
non-motor neurons virtually eliminates spontaneous flight turns while preserving
the tethered flies' ability to perform two types of visually evoked turns,
demonstrating that, at least in flies, these two modes of action are almost
completely dissociable.
PMID- 29337082
TI - Serum lactate dehydrogenase isoenzymes 4 plus 5 is a better biomarker than total
lactate dehydrogenase for refractory Mycoplasma pneumoniae pneumonia in children.
AB - Although usually self-limiting, Mycoplasma pneumoniae pneumonia (MPP) may lead to
clinical or radiological deterioration despite macrolide antibiotic therapy,
resulting in the development of refractory MPP (RMPP). Corticosteroids have been
used to treat RMPP with beneficial effects. Serum lactate dehydrogenase (LDH) is
a suggested biomarker for the use of steroid therapy. Since serum LDH is a non
specific marker and elevated in many inflammatory processes, this study
investigates the predicting level of LDH isoenzymes for RMPP. Fifty-four children
with non-refractory M. pneumoniae pneumonia (NRMPP) and 16 children with RMPP
were enrolled in this study. In comparison to the NRMPP group, the RMPP group
showed significantly higher levels of serum LDH. Concerning LDH isoenzymes, the
RMPP group showed significantly lower proportions of LDH1 and LDH2, while higher
LDH4 and LDH5 percentage. Receiver operating characteristic curve analysis showed
that the area under the curve for the total LDH data was 0.812 with a cut-off of
408 IU/L (sensitivity of 75.0%, specificity of 72.2%). The areas under the curve
for LDH4, LDH5, and [LDH4 + LDH5] were estimated to be 0.813, 0.818, and 0.829,
respectively. The threshold for [LDH4 + LDH5] was estimated to be 109.4 IU/L
(sensitivity, 75.0%; specificity, 87.0%). These results indicate that for the
initiation of corticosteroid therapy, serum [LDH4 + LDH5] level is a more
sensitive biomarker than total LDH.
PMID- 29337083
TI - Palmitoylethanolamide attenuates cocaine-induced behavioral sensitization and
conditioned place preference in mice.
AB - Cocaine addiction is a chronically relapsing disorder characterized by compulsive
drug-seeking and drug-taking behaviors. Previous studies have demonstrated that
cocaine, as well as other drugs of abuse, alters the levels of lipid-based
signaling molecules, such as N-acylethanolamines (NAEs). Moreover, brain levels
of NAEs have shown sensitivity to cocaine self-administration and extinction
training in rodents. Given this background, the aim of this study was to
investigate the effects of repeated or acute administration of
palmitoylethanolamide (PEA), an endogenous NAE, on psychomotor sensitization and
cocaine-induced contextual conditioning. To this end, the potential ability of
repeated PEA administration (1 or 10 mg/kg, i.p.) to modulate the acquisition of
cocaine-induced behavioral sensitization (BS) and conditioned place preference
(CPP) was assessed in male C57BL/6J mice. In addition, the expression of cocaine
induced BS and CPP following acute PEA administration were also studied. Results
showed that repeated administration of both doses of PEA were able to block the
acquisition of cocaine-induced BS. Furthermore, acute administration of both
doses of PEA was able to abolish the expression of BS, while the highest dose
also abolished the expression of cocaine-induced CPP. Taken together, these
results indicate that exogenous administration of PEA attenuated psychomotor
sensitization, while the effect of PEA in cocaine-induced CPP depended on whether
PEA was administered repeatedly or acutely. These findings could be relevant to
understand the role that NAEs play in processes underlying the development and
maintenance of cocaine addiction.
PMID- 29337084
TI - A graph-based approach to analyze flux-balanced pathways in metabolic networks.
AB - An elementary flux mode (EFM) is a pathway with minimum set of reactions that are
functional in steady-state constrained space. Due to the high computational
complexity of calculating EFMs, different approaches have been proposed to find
these flux-balanced pathways. In this paper, an approach to find a subset of EFMs
is proposed based on a graph data model. The given metabolic network is mapped to
the graph model and decisions for reaction inclusion can be made based on
metabolites and their associated reactions. This notion makes the approach more
convenient to categorize the output pathways. Implications of the proposed method
on metabolic networks are discussed.
PMID- 29337085
TI - DISC: Describing Infections of the Spine treated with Ceftaroline.
AB - OBJECTIVES: Infections of the spine lead to considerable morbidity and a high
cost to the global healthcare system. Currently, evidence for using ceftaroline,
an advanced-generation cephalosporin active against methicillin-resistant
Staphylococcus aureus (MRSA), in spine infections is limited. METHODS: Describing
Infections of the Spine treated with Ceftaroline (DISC) is a multicentre,
retrospective, cohort study that evaluated ceftaroline for treating spine
infections. Patients were included if they were aged >=18 years, diagnosed with a
spine infection and treated with ceftaroline for >=28 days. A control group was
identified with the same inclusion criteria as the study population except they
were treated with a comparator antibiotic for >=28 days. RESULTS: Thirty-seven
patients were included each in the ceftaroline and control groups. MRSA was the
most commonly identified pathogen. With no differences between groups in age,
sex, race or co-morbidities (with the exception of chronic kidney disease),
treatment with ceftaroline led to similar clinical success compared with the
control group. Multivariate regression analysis did not show a significant
difference between the two groups in terms of clinical success after controlling
for other covariates (adjusted odds ratio=1.49; P=0.711). More patients who
received ceftaroline were discharged to an extended-care or rehabilitation
facility than home compared with controls (81% vs. 54%, respectively; P=0.024).
Side effects and toxicities were rare, including one case of eosinophilic
pneumonia in the ceftaroline group. CONCLUSIONS: Ceftaroline appears to be a safe
and effective therapy for infections of the spine, including from MRSA.
PMID- 29337086
TI - Incidental Pulmonary Nodules Are Common on CT Coronary Angiogram and Have a
Significant Cost Impact.
AB - BACKGROUND: Computed tomography (CT) coronary angiogram (CTCA) is commonly used
for diagnostic evaluation of low-moderate risk patients due to its excellent
performance and cost-effectiveness. However, previous cost analyses have not
factored in the burden of management of pulmonary nodules, which are a common
occurrence. We sought to describe the frequency and characteristics of lung
nodules on CTCA in an Australian tertiary hospital, and to assess cost impacts.
METHODS: Consecutive CTCAs performed in the calendar year 2012 were
retrospectively identified from the imaging department database. Subjects were
excluded if they were under the age of 35, had known malignancy or findings
identified prior to CTCA. Patients were stratified on smoking history and nodule
size. RESULTS: Of the 2479 CTCAs included, full-field imaging revealed nodules in
358 patients (13.9%). The nodules were generally small (73% <6mm), multiple (63%)
and in the lower lobe (83.4%). There was no significant difference when
stratified for smoking, with 60% of nodules detected in never-smokers. A minimum
of 445 subsequent scans was required for nodule surveillance, resulting in an
additional overall cost of $63.62 per CTCA. Limited-Field-of-View (L-FOV) would
have identified only 22 nodules, with a cost of $6.14 for every CTCA performed, a
cost saving of $57 per patient. CONCLUSIONS: Indeterminate pulmonary nodules are
a common incidental finding on CTCA and prevalence appears to be independent of
smoking status. There is a consequent significant cost burden that has not
previously been recognised. Use of L-FOV reduces the number of nodules
identified, with a significant cost benefit, but this has to be balanced against
the ethical and medico-legal issues inherent in not reconstructing the irradiated
lung.
PMID- 29337087
TI - Genetic polymorphisms of pharmacogenomic VIP variants in the Yi population from
China.
AB - INTRODUCTION: Drug response and target therapeutic dosage are different among
individuals. The variability is largely genetically determined. With the
development of pharmacogenetics and pharmacogenomics, widespread research have
provided us a wealth of information on drug-related genetic polymorphisms, and
the very important pharmacogenetic (VIP) variants have been identified for the
major populations around the world whereas less is known regarding minorities in
China, including the Yi ethnic group. Our research aims to screen the potential
genetic variants in Yi population on pharmacogenomics and provide a theoretical
basis for future medication guidance. MATERIALS AND METHODS: In the present
study, 80 VIP variants (selected from the PharmGKB database) were genotyped in
100 unrelated and healthy Yi adults recruited for our research. Through
statistical analysis, we made a comparison between the Yi and other 11
populations listed in the HapMap database for significant SNPs detection. Two
specific SNPs were subsequently enrolled in an observation on global allele
distribution with the frequencies downloaded from ALlele FREquency Database.
Moreover, F-statistics (Fst), genetic structure and phylogenetic tree analyses
were conducted for determination of genetic similarity between the 12 ethnic
groups. RESULTS: Using the chi2 tests, rs1128503 (ABCB1), rs7294 (VKORC1),
rs9934438 (VKORC1), rs1540339 (VDR) and rs689466 (PTGS2) were identified as the
significantly different loci for further analysis. The global allele distribution
revealed that the allele "A" of rs1540339 and rs9934438 were more frequent in Yi
people, which was consistent with the most populations in East Asia. F-statistics
(Fst), genetic structure and phylogenetic tree analyses demonstrated that the Yi
and CHD shared a closest relationship on their genetic backgrounds. Additionally,
Yi was considered similar to the Han people from Shaanxi province among the
domestic ethnic populations in China. CONCLUSIONS: Our results demonstrated
significant differences on several polymorphic SNPs and supplement the
pharmacogenomic information for the Yi population, which could provide new
strategies for optimizing clinical medication in accordance with the genetic
determinants of drug toxicity and efficacy.
PMID- 29337088
TI - Cross-regulatory network in Pseudomonas aeruginosa biofilm genes and TiO2 anatase
induced molecular perturbations in key proteins unraveled by a systems biology
approach.
AB - A systems biology approach was used to study all the biofilm related genes of P.
aeruginosa PAO1, and the interaction of titanium dioxide (TiO2) anatase with
biofilm related proteins. Among the 71 genes, the interactions of all the nodal
pairs were extracted by STRING 10.5 database. The inter-relationship among these
genes was predicted by constructing complete PPI network and visualized in
Cytoscape v 3.4.0. Total number of nodes of the network was found to be 335 and
edges were 795. The network was further investigated for its clusters and the
best cluster was further analyzed for the hub proteins which significantly
contribute in cross-regulation of the biofilm related process. The hub proteins
were identified based on four topological parameters of degree, closeness,
betweeness and radiality. Four major hub proteins of P. aeruginosa PAO1 were
identified to be algD, gacS, rpoS and rpoN which were common in all the hubs.
Further, we have also elucidated the probable mechanism of TiO2 interaction with
P. aeruginosa PAO1 at molecular level. Using STITCH server, the major target gene
of TiO2 was identified as katA which also appeared commonly in our main dataset
and this gene has been focused for the further study because of its unique common
appearance in gene-gene network as well as gene-anatase network. The direct
interacting partners of katA were found to be dnaK, hfq, rpoS and rpoA. Based on
these findings and available gene regulatory information, probable TiO2
interacting cascade has been represented. This in silico study of P. aeruginosa
PAO1 biofilm genes and the interaction of protein products with TiO2 might be
significant to understand the perspective pathogenic resistance as well as the
toxicity research pertaining to nanoparticles.
PMID- 29337089
TI - Thermal Field Distributions of Ablative Experiments Using Cyst-mimicking
Phantoms: Comparison of Microwave and Radiofrequency Ablation.
AB - RATIONALE AND OBJECTIVES: The objective of this study was to explore the thermal
field distribution of cystic lesions undergoing microwave ablation (MWA) and
radiofrequency ablation (RFA) using in vitro phantoms. MATERIALS AND METHODS:
Cyst-mimicking lesions filled with sodium chloride (NaCl) solution in acrylamide
phantoms were treated with MWA and RFA in vitro. The radiofrequency electrodes or
MWA antennas were implanted in the centers of the artificial cystic lesions. We
used temperature fields located 5, 15, and 25 mm from the electrode or the
antenna to plot the temperature-rise curves. Solid phantoms without cysts were
also fabricated as controls. RESULTS: The temperature within cysts increased
faster and reached a higher maximum temperature during MWA than during RFA, and
this result was independent of the NaCl solution concentration. RFA treatment
caused the temperatures within the lesion to increase significantly faster in the
cysts containing 0.9% NaCl than in those containing 5.0% NaCl. However, the MWA
temperature-rise curves were only weakly affected by the ionic concentration. The
median temperature difference values between the 5- and 15-mm points were
markedly lower in the 0.9% NaCl cyst-mimicking phantom (P <0.001) than in the
solid phantom after either MWA or RFA. CONCLUSIONS: Our data indicate that MWA is
a more effective technique for focal cystic lesions than RFA and has higher
overall energy utilization. MWA was also less affected by the ionic concentration
of the cystic fluid.
PMID- 29337090
TI - The Clinical Impact of Resident-attending Discrepancies in On-call Radiology
Reporting: A Retrospective Assessment.
AB - RATIONALE AND OBJECTIVES: The purpose of this study is to quantify the clinical
impact of resident-attending discrepancies at a tertiary referral academic
radiology residency program by assessing rates of intervention, discrepancy
confirmation, recall rate, and management change rate; furthermore, a discrepancy
categorization system will be assessed. MATERIALS AND METHODS: Retrospective
review of the records was performed for n = 1482 discrepancies that occurred in
the 17-month study period to assess the clinical impact of discrepancies.
Discrepancies were grouped according to a previously published classification
system. Management changes were recorded and grouped by severity. The recall rate
was estimated for discharged patients. Any confirmatory testing was reviewed to
evaluate the accuracy of the discrepant report. Categorical variables were
compared to the chi-square test. RESULTS: The 1482 discrepancies led to
management change in 661 cases (44.6%). The most common management change was
follow-up imaging. Procedural interventions including surgery occurred in 50
cases (3.3%). The recall rate was 2.6%. Management changes were more severe with
computed tomography examinations, inpatients, and when the discrepancy was in the
chest and abdomen subspecialty. Also, management changes correlated with the
discrepancy category assigned by the attending at the time of review.
CONCLUSIONS: Resident-attending discrepancies do cause management changes in
44.6% of discrepancies (0.62% overall); the most frequent change is follow-up
imaging. The discrepancy categorization assigned by the attending correlated with
the severity of management change.
PMID- 29337091
TI - A Clinically Meaningful Interpretation of the Prospective Investigation of
Pulmonary Embolism Diagnosis (PIOPED) II and III Data.
AB - RATIONALE AND OBJECTIVES: This study aimed to calculate the multiple-level
likelihood ratios (LRs) and posttest probabilities for a positive, indeterminate,
or negative test result for multidetector computed tomography pulmonary
angiography (MDCTPA) +/- computed tomography venography (CTV) and magnetic
resonance pulmonary angiography (MRPA) +/- magnetic resonance venography (MRV)
for each clinical probability level (two-, three-, and four-level) for the nine
most commonly used clinical prediction rules (CPRs) (Wells, Geneva, Miniati, and
Charlotte). The study design is a review of observational studies with critical
review of multiple cohort studies. The settings are acute care, emergency room
care, and ambulatory care (inpatients and outpatients). MATERIALS AND METHODS:
Data were used to estimate pulmonary embolism (PE) pretest probability for each
of the most commonly used CPRs at each probability level. Multiple-level LRs
(positive, indeterminate, negative test) were generated and used to calculate
posttest probabilities for MDCTPA, MDCTPA + CTV, MRPA, and MRPA + MRV from
sensitivity and specificity results from Prospective Investigation of Pulmonary
Embolism Diagnosis (PIOPED) II and PIOPED III for each clinical probability level
for each CPR. Nomograms were also created. RESULTS: The LRs for a positive test
result were higher for MRPA compared to MDCTPA without venography (76 vs 20) and
with venography (42 vs 18). LRs for a negative test result were lower for MDCTPA
compared to MRPA without venography (0.18 vs 0.22) and with venography (0.12 vs
0.15). In the three-level Wells score, the pretest clinical probability of PE for
a low, moderate, and high clinical probability score is 5.7, 23, and 49. The
posttest probability for an initially low clinical probability PE for a positive,
indeterminate, and negative test result, respectively, for MDCTPA is 54, 5 and 1;
for MDCTPA + CTV is 52, 2, and 0.7; for MRPA is 82, 6, and 1; and for MRPA + MRV
is 72, 3, and 1; for an initially moderate clinical probability PE for MDCTPA is
86, 22, and 5; for MDCTPA + CTV is 85, 10, and 4; for MRPA is 96, 25, and 6; and
for MRPA + MRV is 93, 14, and 4; and for an initially high clinical probability
of PE for MDCTPA is 95, 47, and 15; for MDCTPA + CTV is 95, 27, and 10; for MRPA
is 99, 52, and 17; and for MRPA + MRV is 98, 34, and 13. CONCLUSIONS: For a
positive test result, LRs were considerably higher for MRPA compared to MDCTPA.
However, both a positive MRPA and MDCTPA have LRs >10 and therefore can confirm
the presence of PE. Performing venography reduced the LR for a positive and
negative test for both MDCTPA and MRPA. The nomograms give posttest probabilities
for a positive, indeterminate, or negative test result for MDCTPA and MRPA (with
and without venography) for each clinical probability level for each of the CPR.
PMID- 29337093
TI - Breast cancer in young women: do BRCA1 or BRCA2 mutations matter?
PMID- 29337092
TI - Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a
prospective cohort study.
AB - BACKGROUND: Retrospective studies provide conflicting interpretations of the
effect of inherited genetic factors on the prognosis of patients with breast
cancer. The primary aim of this study was to determine the effect of a germline
BRCA1 or BRCA2 mutation on breast cancer outcomes in patients with young-onset
breast cancer. METHODS: We did a prospective cohort study of female patients
recruited from 127 hospitals in the UK aged 40 years or younger at first
diagnosis (by histological confirmation) of invasive breast cancer. Patients with
a previous invasive malignancy (except non-melanomatous skin cancer) were
excluded. Patients were identified within 12 months of initial diagnosis. BRCA1
and BRCA2 mutations were identified using blood DNA collected at recruitment.
Clinicopathological data, and data regarding treatment and long-term outcomes,
including date and site of disease recurrence, were collected from routine
medical records at 6 months, 12 months, and then annually until death or loss to
follow-up. The primary outcome was overall survival for all BRCA1 or BRCA2
mutation carriers (BRCA-positive) versus all non-carriers (BRCA-negative) at 2
years, 5 years, and 10 years after diagnosis. A prespecified subgroup analysis of
overall survival was done in patients with triple-negative breast cancer.
Recruitment was completed in 2008, and long-term follow-up is continuing.
FINDINGS: Between Jan 24, 2000, and Jan 24, 2008, we recruited 2733 women.
Genotyping detected a pathogenic BRCA mutation in 338 (12%) patients (201 with
BRCA1, 137 with BRCA2). After a median follow-up of 8.2 years (IQR 6.0-9.9), 651
(96%) of 678 deaths were due to breast cancer. There was no significant
difference in overall survival between BRCA-positive and BRCA-negative patients
in multivariable analyses at any timepoint (at 2 years: 97.0% [95% CI 94.5-98.4]
vs 96.6% [95.8-97.3]; at 5 years: 83.8% [79.3-87.5] vs 85.0% [83.5-86.4]; at 10
years: 73.4% [67.4-78.5] vs 70.1% [67.7-72.3]; hazard ratio [HR] 0.96 [95% CI
0.76-1.22]; p=0.76). Of 558 patients with triple-negative breast cancer, BRCA
mutation carriers had better overall survival than non-carriers at 2 years (95%
[95% CI 89-97] vs 91% [88-94]; HR 0.59 [95% CI 0.35-0.99]; p=0.047) but not 5
years (81% [73-87] vs 74% [70-78]; HR 1.13 [0.70-1.84]; p=0.62) or 10 years (72%
[62-80] vs 69% [63-74]; HR 2.12 [0.82-5.49]; p= 0.12). INTERPRETATION: Patients
with young-onset breast cancer who carry a BRCA mutation have similar survival as
non-carriers. However, BRCA mutation carriers with triple-negative breast cancer
might have a survival advantage during the first few years after diagnosis
compared with non-carriers. Decisions about timing of additional surgery aimed at
reducing future second primary-cancer risks should take into account patient
prognosis associated with the first malignancy and patient preferences. FUNDING:
Cancer Research UK, the UK National Cancer Research Network, the Wessex Cancer
Trust, Breast Cancer Now, and the PPP Healthcare Medical Trust Grant.
PMID- 29337094
TI - Vitamin D attenuates pressure overload-induced cardiac remodeling and dysfunction
in mice.
AB - Vitamin D (VD) and its analogues play critical roles in metabolic and
cardiovascular diseases. Recent studies have demonstrated that VD exerts a
protective role in cardiovascular diseases. However, the beneficial effect of VD
on pressure overload-induced cardiac remodeling and dysfunction and its
underlying mechanisms are not fully elucidated. In this study, cardiac
dysfunction and hypertrophic remodeling in mice were induced by pressure
overload. Cardiac function was evaluated by echocardiography, and myocardial
histology was detected by H&E and Masson's trichrome staining. Cardiomyocyte size
was detected by wheat germ agglutinin staining. The protein levels of signaling
mediators were examined by western blotting while mRNA expression of hypertrophic
and fibrotic markers was examined by qPCR analysis. Oxidative stress was detected
by dihydroethidine staining. Our results showed that administration of VD3
significantly ameliorates pressure overload-induced contractile dysfunction,
cardiac hypertrophy, fibrosis and inflammation in mice. In addition, VD3
treatment also markedly inhibited cardiac oxidative stress and apoptosis.
Moreover, protein levels of calcineurin A, ERK1/2, AKT, TGF-beta, GRP78, cATF6,
and CHOP were significantly reduced whereas SERCA2 level was upregulated in the
VD3-treated hearts compared with control. These results suggest that VD3
attenuates cardiac remodeling and dysfunction induced by pressure overload, and
this protective effect is associated with inhibition of multiple signaling
pathways.
PMID- 29337095
TI - Development of native and modified banana starch nanoparticles as vehicles for
curcumin.
AB - In recent years, starch nanoparticles have been of great interest for drug
delivery due to their relatively easy synthesis, biocompatibility, and vast
amount of botanical sources. Native and acetylated starch obtained from green
bananas were used for synthesis of curcumin-loaded starch nanoparticles. Mean
particle size, encapsulation efficiency, and curcumin release in simulated
gastric and intestinal fluids were studied. Both nanosystems showed sizes lower
than 250 nm and encapsulation efficiency above 80%, with acetylated banana starch
nanoparticles having the capacity to encapsulate more curcumin molecules. Both
FTIR and XRD analyses showed that starch acetylation allows stronger hydrogen
bond interaction between curcumin and the starch matrix, thus, higher
encapsulation efficiency. Finally, curcumin release studies showed that
acetylated banana starch nanoparticles allowed more controlled release, probably
due to their stronger hydrogen bond interaction with curcumin.
PMID- 29337096
TI - Fabrication and characterization of nanoengineered biocompatible n-HA/chitosan
tamarind seed polysaccharide: Bio-inspired nanocomposites for bone tissue
engineering.
AB - In this communication we describe the fabrication of nano-hydroxyapatite/chitosan
tamarind seed polysaccharide (n-HA/CS-TSP) nanocomposite with a weight ratio of
70/20/10, 70/15/15 and 70/10/20, respectively through a co-precipitation method.
A comparative assessment of the properties of n-HA/CS-TSP and n-HA/CS
nanocomposites was done by FT-IR, SEM-EDX, TEM, TGA/DTA, XRD and mechanical
testing. The results suggested strong chemical interactions between the three
components, decreased particle size and homogeneous dispersion of n-HA particles
in n-HA/CS-TSP as compared to n-HA/CS. The n-HA/CS-TSP (70/10/20) showed the most
porous and rough surface, enhanced thermal stability and highest compressive
strength (4.0 MPa) and modulus (81 MPa). In addition, n-HA/CS-TSP (70/10/20)
exhibited greater swelling character, acceptable degradation and increased
biomineralization in simulated body fluid (SBF) as compared to n-HA/CS-TSP
(70/20/10, 70/15/15) and n-HA/CS nanocomposites. The superior non-toxic response
with MG-63 cells and better haemocompatibility was observed with n-HA/CS-TSP
(70/15/15). Thereby, n-HA/CS-TSP nanocomposites could be promising alternative
biomaterials in the field of bone tissue engineering compared to the n-HA/CS
nanocomposite.
PMID- 29337097
TI - Physical and antimicrobial properties of starch-carboxy methyl cellulose film
containing rosemary essential oils encapsulated in chitosan nanogel.
AB - This study was set to prepare a new active film by using a biodegradable bio
based source, i.e., corn starch. To achieve that, benzoic acid (BA) and chitosan
(CS) were covalently bound and CS-BA nanogel was then obtained using self
assembly method. Subsequently, rosemary essential oil (REO) was encapsulated in
CS-BA nanogel. Finally, REO in both free and encapsulated forms were incorporated
in starch-carboxy methyl cellulose (CMC) films and their physical, mechanical and
antimicrobial properties were studied. The films incorporating CS-BA nanogel had
a higher water vapor permeability compared with the films containing REO.
Moreover, film containing 0.2% CS-BA nanogel had the highest transparency and
tensile strength. The REO and nanogel alone had inhibitory effects against
Staphylococcus aureus (S. aureus) and by encapsulation, the inhibitory effect of
REO was increased. By encapsulating REO in nanogel, both immediately (REO) and
gradual (Nanogel) antimicrobial effect against S. aureus in the starch-CMC
suspensions were obtained.
PMID- 29337098
TI - Synthesis and characterization of chitin/curcumin blended polyurethane
elastomers.
AB - In this work, chitin-curcumin based polyurethane elastomers (PUEs) were prepared
by step growth polymerization technique using hydroxy terminated polybutadiene
(HTPB), hexamethylene diisocyanate (HDI), chitin and curcumin. The molecular
characterization was done by using FTIR and SS 1HNMR techniques. The surface
morphology and thermal stability was studied by scanning electron microscopy
(SEM) and thermal gravimetric analysis (TGA), respectively. Degree of absorption
and swelling characters were also determined in water as well as in DMSO. The
crystalline behavior of prepared elastomers was checked by using X-ray
diffraction (XRD) and differential scanning calorimeter (DSC). Results presented
that crystallinity of elastomers increased by increasing the content of chitin
due to formation of more ordered structure.
PMID- 29337099
TI - Facile preparation and characterization of pH sensitive Mt/CMC nanocomposite
hydrogel beads for propranolol controlled release.
AB - The main aim of the present study was to design pH-sensitive nanocomposite
hydrogel beads, based on carboxymethyl cellulose (CMC) and montmorillonite (Mt)
propranolol (PPN) nanohybrid, and evaluate whether the prepared nanocomposite
beads could potentially be used as oral drug delivery systems. PPN-as a model
drug-was intercalated into the interlayer space of Mt clay mineral via the ion
exchange procedure. The resultant nanohybrid (Mt-PPN) was applied to fabricate
nanocomposite hydrogel beads by association with carboxymethyl cellulose. The
characterization of test samples was performed using different techniques: X-Ray
Diffraction (XRD), IR spectroscopy (FT-IR), thermal gravity analysis (TGA), and
scanning electron microscopy (SEM). The drug encapsulation efficiency was
evaluated by UV-vis spectroscopy, and was found to be high for Mt/CMC beads. In
vitro drug release test was performed in the simulated gastrointestinal
conditions to evaluate the efficiency of Mt-PPN/CMC nanocomposite beads as a
controlled-release drug carrier. The drug release profiles indicated that the Mt
PPN/CMC nanocomposite beads had high stability against stomach acid and a
sustained- and controlled-release profile for PPN under the simulated intestinal
conditions.
PMID- 29337100
TI - Knockdown of long non-coding RNA XIST inhibits cell viability and invasion by
regulating miR-137/PXN axis in non-small cell lung cancer.
AB - Long non-coding RNAs (lncRNAs) may serve as miRNA sponges to modulate the
expressions of miRNA target genes. LncRNA X-inactive specific transcript (XIST)
has been demonstrated to be upregulated and act as an oncogene in non-small cell
lung cancer (NSCLC). However, the sponge role of XIST in NSCLC progression
remains largely unknown. In this study, we demonstrated that XIST was
substantially upregulated and miR-137 was aberrantly downregulated in NSCLC
tissues and cells. XIST was identified to function as a competitive endogenous
RNA (ceRNA) for miR-137 to promote NSCLC cell viability and invasion.
Additionally, our results suggested that miR-137 targeted the 3'UTR of paxillin
(PXN) to suppress NSCLC cell viability and invasion. Meanwhile, miR-137 was
negatively correlated with PXN expression while XIST was positively correlated
with PXN expression. More importantly, XIST positively regulated PXN levels by
sponging miR-137 in vitro and in vivo. Collectively, our study provided the
evidence for the cross-talk between XIST, miR-137, and PXN, shedding light on the
therapy for NSCLC.
PMID- 29337101
TI - Extracellular polysaccharide from Weissella confusa OF126: Production,
optimization, and characterization.
AB - The production, optimization, and characterization of exopolysaccharide (EPS)
from Weissella confusa OF126 and the in-vitro probiotic potentials of this strain
was investigated. The EPS produced on sucrose modified-MRS broth was
characterized. The purified EPS had an average molecular weight of 1.1 * 106 Da.
HPLC analysis revealed the presence of glucose monomers, indicating its
homopolysaccharide nature. The structural characteristics of the EPS were
investigated by FTIR, and NMR spectroscopy. FTIR spectroscopy revealed the
presence of hydroxyl, carboxyl, N-acetyl and amine groups. NMR analysis confirmed
that the EPS contained alpha-(1 -> 6) linkage and alpha-(1 -> 3) branched
linkage. The EPS showed strong in-vitro antioxidant activity. Four significant
factors were optimized using Central Composite Design (CCD) and Response Surface
Methodology (RSM). The predicted optimum conditions for EPS production were
cultivation time (48.50 h), sucrose concentration (24.00 g/L), pH (7.00) and
yeast extract (2.50%).The EPS produced was predicted to be 3.10 g/L, while the
experimental yield was 3.00 g/L. This strain was found to possess desirable
probiotic attributes by its ability to survive at pH 2.0 and in the presence of
bile salts (0.50% (w/v)) for 4 h. The results obtained from this study
demonstrate W. confusa OF126 as a promising probiotic and the EPS produced can
find useful applications in industries.
PMID- 29337102
TI - Polymeric microspheres of okra mucilage and alginate for the controlled release
of oxcarbazepine: In vitro &in vivo evaluation.
AB - Oxcarbazepine-loaded alginate/okra pods mucilage microspheres were prepared
through inotropic gelation technique for the sustained release of oxcarbazepine.
The drug encapsulating efficiency of these microspheres was found 76.22 +/- 0.01%
to 90.57 +/- 0.02% and their average particle sizes were 496 MUm +/- 0.41 to 692
MUm +/- 0.22. These microspheres were characterized in terms of swelling
capacity, FTIR, DSC and SEM analysis. The in vitro drug release from these
microspheres was followed sustained release (Korsemeyer - Peppas model) pattern
(R2 = 0.9552-0.9906) and value of n > 1 showed that drug released by anomalous
(non-Fickian) diffusion. The in vivo studies showed that there were highly
significant difference with p < 0.001 in the pharmacokinetic parameters (Cmax,
t1/2, AUC0-infinity, Ke), when oxcarbazepine was formulated in form of polymeric
microspheres as compared to pure drug.
PMID- 29337103
TI - Green options for imparting antibacterial functionality to cotton fabrics.
AB - This study demonstrated that antibacterial cellulosic textiles can be fabricated
in eco-friendly manner by grafting of monochlorotriazinyl beta-cyclodextin (MCT
betaCD) onto knitted and woven cotton fabrics followed by post-loading of any of
the green active ingredients namely Rosemary oil, Lavender oil, Clove oil,
Cinnamon oil, Aloe vera gel, Vanillin, Ag-ions, Natural Yellow 7 and Natural Red
25 dyes into the hydrophobic cavities of grafted beta-CD moieties. Some of the
grafted, post-loaded fabric samples were characterized by FTIR, SEM, and EDS
analysis. The enhancement in the imparted antibacterial functionality as well as
durability to wash are governed by type of cellulosic substrate, kind, chemistry,
antibacterial activity as well as extent of inclusion and subsequent release of
the hosted bioactive agent. The obtained results revealed that the antibacterial
efficacy follows the deceasing orders: i) knitted fabric > woven fabric and ii)
Ag-ions > Lavender oil > Natural Yellow 7 > Aloe vera > Cinnamon oil > Natural
Red 25 > Vanillin > Clove oil > Rosemary oil-loaded fabric sample, keeping other
parameters constant.
PMID- 29337104
TI - Bioactive potential and composition analysis of sulfated polysaccharide from
Acanthophora spicifera (Vahl) Borgeson.
AB - Marine seaweeds contain a valuable source of functional bioactive polysaccharide
and it plays main role for effective anticancer activity. The structural feature
of SPs was studied through FT-IR and 1H NMR spectra analysis. The isolated SPs
from A. spicifera contain 63.3% of total sugar, 21.9% of total sulfate and 12.6%
of total uranic acid was found. The active F2 fraction molecular weight of SP was
found to be 420 kDa. The sugar was composed of galactose (73.5%), xylose (9.2%),
mannose (1.9%) and arabinose (10.9%). Further the SP showed DPPH free radical
scavenging activity of 55.55% at 150 MUg/mL and reducing power activity of 91.3%
at 125 MUg/mL. In the present study, the purified sulfated polysaccharide
(fraction F2) were extracted, purified and characterized for red seaweed and
evaluated for their potential anticancer activity of in A549 cell lines under in
vitro condition. These polysaccharide fractions exhibited potential apoptotic
effects on A549 cell lines.
PMID- 29337105
TI - Chitosan/sodium tripolyphosphate nanoparticles as efficient vehicles for
antioxidant peptidic fraction from common kilka.
AB - Fish-purified antioxidant peptide (AOP)-loaded chitosan nanoparticles (CSNPs)
were synthesized based on the ionotropic gelation between CS and sodium
tripolyphosphate (TPP). The zeta-potential showed an earlier rise and later
decrease with increasing concentrations of AOP. Transmission electron microscopy
(TEM) images also revealed roughly uniform spherical-shaped nanoparticles with
diameter of <100 nm. Molecular interactions among the components of the NPs and
peptides were confirmed by FT-IR spectroscopy. Thermo-gravimetric analysis (TGA)
results showed the improved thermal stability of the AOP-loaded CSNPs compared
with free peptides. The maximum peptide encapsulation efficiency was determined
to be 71.16% and the in vitro release of peptides from CSNPs was in a
controllable manner. Furthermore, assessing the free radical scavenging ability
of the peptide-encapsulated NPs and the reducing power assay, confirmed the
efficacy of such nanosystem in retaining the antioxidant activity of fish-derived
peptides.
PMID- 29337106
TI - Loss of TGF-beta signaling in osteoblasts increases basic-FGF and promotes
prostate cancer bone metastasis.
AB - TGF-beta plays a central role in prostate cancer (PCa) bone metastasis, and it is
crucial to understand the bone cell-specific role of TGF-beta signaling in this
process. Thus, we used knockout (KO) mouse models having deletion of the Tgfbr2
gene specifically in osteoblasts (Tgfbr2Col1CreERT KO) or in osteoclasts
(Tgfbr2LysMCre KO). We found that PCa-induced bone lesion development was
promoted in the Tgfbr2Col1CreERT KO mice, but was inhibited in the Tgfbr2LysMCre
KO mice, relative to their respective control Tgfbr2FloxE2 littermates. Since
metastatic PCa cells attach to osteoblasts when colonized in the bone
microenvironment, we focused on the mechanistic studies using the
Tgfbr2Col1CreERT KO mouse model. We found that bFGF was upregulated in
osteoblasts from PC3-injected tibiae of Tgfbr2Col1CreERT KO mice and correlated
with increased tumor cell proliferation, angiogenesis, amounts of cancer
associated fibroblasts and osteoclasts. In vitro studies showed that
osteoblastogenesis was inhibited, osteoclastogenesis was stimulated, but PC3
viability was not affected, by bFGF treatments. Lastly, the increased PC3-induced
bone lesions in Tgfbr2Col1CreERT KO mice were significantly attenuated by
blocking bFGF using neutralizing antibody, suggesting bFGF is a promising target
inhibiting bone metastasis.
PMID- 29337107
TI - tRNA-derived small non-coding RNAs in human disease.
AB - Besides attending protein synthesis, transfer RNA (tRNA) is an important
regulatory non-coding RNA (ncRNA) that participates in various cellular
processes, including cellular metabolism and cell death. Fragments generated from
pre- or mature tRNAs by specific endonucleases cleavage (tRNA-derived small non
coding RNA [tsncRNAs]), rather than random degradation products, are newly
defined functional small non-coding RNAs (sncRNAs). They can be regulated in
bacteria, yeast, plants and animals to respond to stress conditions, resulting in
regulation of gene expressions at both transcriptional and post-transcriptional
level. Increasing evidence showed that the dysregulation of a series of tsncRNAs
is associated with several types of human disease. In this review, we summarize
the diversity and biogenesis of tsncRNAs in mammals and highlight the functions
and mechanisms of different sub-classes of tsncRNAs in human disease.
PMID- 29337108
TI - A vascular disrupting agent overcomes tumor multidrug resistance by skewing
macrophage polarity toward the M1 phenotype.
AB - Multidrug resistance (MDR) mediated by ATP-binding cassette (ABC) transporters is
the major obstacle for chemotherapeutic success. Although attempts have been made
to circumvent ABC transporter-mediated MDR in past decades, there is still no
effective agent in clinic. Here, we identified a vascular disrupting agent, Z-GP
DAVLBH, that significantly inhibited the growth of multidrug-resistant human
hepatoma HepG2/ADM and human breast cancer MCF-7/ADR tumor xenografts, although
these cells were insensitive to Z-GP-DAVLBH in vitro. Z-GP-DAVLBH increased the
secretion of granulocyte-macrophage colony-stimulating factor in tumor tissues
and serum of tumor-bearing mice to skew tumor-associated macrophages from the pro
tumor M2 phenotype to the antitumor M1 phenotype, thereby contributing to the
induction of HepG2/ADM and MCF-7/ADR cell apoptosis. Our findings shed new light
on the underlying mechanisms of VDAs in the treatment of drug-resistant tumors
and provide strong evidence that Z-GP-DAVLBH should be a promising agent for
overcoming MDR.
PMID- 29337109
TI - Molecular mechanisms of lncRNA SMARCC2/miR-551b-3p/TMPRSS4 axis in gastric
cancer.
AB - Decreased expression of miR-551b-3p has been identified in gastric cancer tissues
but its biological role and underlying mechanism in this malignancy is poorly
understood. In this study, we show that the expression of miR-551b-3p negatively
correlates with the depth of tumour invasion and lymphatic metastasis, but it
positively correlates with tumour differentiation and the patient survival. MiR
551b-3p negatively affects the proliferation, mobility and invasiveness of
gastric cancer cells. LncRNA SMARCC2 inhibits the expression of miR-551b-3p
through binding to its mRNA response elements in gastric cancer cells.
Overexpression of LncRNA SMARCC2 enhances the proliferation and migration of
gastric cancer cells, while inhibition of LncRNA SMARCC2 does the opposite.
TMPRSS4 is a direct target gene of miR-551b-3p. We conclude that miR-551b-3p
functions as a tumour suppressor gene in gastric cancer, and its function is
regulated by LncRNA SMARCC2/miR-551b-3p/TMPRSS4 axis.
PMID- 29337110
TI - MUC16 C terminal-induced secretion of tumor-derived IL-6 contributes to tumor
associated Treg enrichment in pancreatic cancer.
AB - Pancreatic cancer is the most lethal tumor. CA125 (gene symbol MUC16) is an
important serum marker for pancreatic cancer diagnosis and treatment. High serum
CA125 is related to metabolic tumor burden and poor prognosis. The circulating
Treg subset is another independent prognostic factor for pancreatic cancer. Our
unpublished data indicated that the circulating Treg proportion might be related
to the serum CA125 level. However, the potential relationship and underlying
mechanism of MUC16 and Treg in pancreatic cancer tissues remain unclear. In this
study, we found that pancreatic cancer tissues were positive for both MUC16 C
terminal (MUC16c) and Foxp3 expression and that their expression was correlated.
MUC16c released into the cytoplasm via EGF induction significantly increased IL-6
expression and secretion. The PI3K/AKT pathway may participate in the regulation
of IL-6 expression and secretion. By treating CD4+ T cells with IL-6 or co
culturing the cells with pancreatic cancer cells, tumor-derived IL-6 was
identified to promote Foxp3 expression and Treg differentiation, which was
significantly inhibited by the JAK2 inhibitor AG-490. In sum, our study
demonstrated that the relationship between the MUC16c level and Foxp3 expression
in the local tumor environment was consistent with that of the serum CA125 level
and circulating Treg proportion in the systemic environment. MUC16c promoted
Foxp3 expression and tumor-associated Treg enrichment in tumor tissues through
tumor-secreted IL-6 activation of the JAK2/STAT3 pathway. These findings may
provide deeper insight into potential pancreatic cancer therapy approaches.
PMID- 29337111
TI - Early re-staging and molecular subtype shift surveillance of locally recurrent or
metastatic breast cancer: A new PET/CT integrated precise algorithm.
AB - Recurrent breast cancer poses considerable diagnostic and therapeutic challenges
for clinic. Clinical suspicion of recurrence must be first confirmed by imaging
studies. Then re-biopsy of suspected recurrence and metastasis in patients with
breast cancer is recommended in the practice guidelines of the National
Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology
(ESMO) to confirm whether the molecular subtype changes. It may change the
individual treatment plan directly. Our research provided an integrated algorithm
for locally recurrent or distant metastatic breast cancer, including early
relapse detection and subsequently a new practical PET/CT imaging guide biopsy
approach for surveilling molecular subtype shifts of the recurrent breast cancer.
In our results, 18F-FDG PET/CT appears to be more sensitive and accurate than
conventional imaging technologies in early detecting locally recurrent or
metastatic breast cancer. PET/CT-guided percutaneous FDG-avid target biopsies
offers a new integrated precise re-biopsy algorithm for pathologic confirm and
surveillance of molecular subtype shifts of the recurrent breast cancer. The
precise algorithm for breast cancer recurrence and metastasis can be established
in one stop, opening a window of opportunity for breast cancer patients to
improve precise individual therapy and prolong survival.
PMID- 29337112
TI - Molecular heterogeneity in diffuse large B-cell lymphoma and its implications in
clinical diagnosis and treatment.
AB - Over half of patients with diffuse large B-cell lymphoma (DLBCL) can be cured by
standard R-CHOP treatment (rituximab, cyclophosphamide, doxorubicin, vincristine,
and prednisone). However, the remaining patients are refractory and ultimately
succumb to progressive or relapsed disease. During the past decade, there has
been significant progress in the understanding of molecular mechanisms in DLBCL,
largely owing to collaborative efforts in large-scale gene expression profiling
and deep sequencing, which have identified genetic alterations critical in
lymphomagenesis through activation of key signaling transduction pathways in
DLBCL. These discoveries have not only led to the development of targeted
therapies, including several currently in clinical trials, but also laid a solid
foundation for the future identification of more effective therapies for patients
not curable by R-CHOP. This review summarizes the recent advances in our
understanding of the molecular characterization and pathogenesis of DLBCL and new
treatment directions.
PMID- 29337113
TI - Volta phase plate data collection facilitates image processing and cryo-EM
structure determination.
AB - A current bottleneck in structure determination of macromolecular complexes by
cryo electron microscopy (cryo-EM) is the large amount of data needed to obtain
high-resolution 3D reconstructions, including through sorting into different
conformations and compositions with advanced image processing. Additionally, it
may be difficult to visualize small ligands that bind in sub-stoichiometric
levels. Volta phase plates (VPP) introduce a phase shift in the contrast transfer
and drastically increase the contrast of the recorded low-dose cryo-EM images
while preserving high frequency information. Here we present a comparative study
to address the behavior of different data sets during image processing and
quantify important parameters during structure refinement. The automated data
collection was done from the same human ribosome sample either as a conventional
defocus range dataset or with a Volta phase plate close to focus (cfVPP) or with
a small defocus (dfVPP). The analysis of image processing parameters shows that
dfVPP data behave more robustly during cryo-EM structure refinement because
particle alignments, Euler angle assignments and 2D & 3D classifications behave
more stably and converge faster. In particular, less particle images are required
to reach the same resolution in the 3D reconstructions. Finally, we find that
defocus range data collection is also applicable to VPP. This study shows that
data processing and cryo-EM map interpretation, including atomic model
refinement, are facilitated significantly by performing VPP cryo-EM, which will
have an important impact on structural biology.
PMID- 29337114
TI - Pathological Endogenous alpha-Synuclein Accumulation in Oligodendrocyte Precursor
Cells Potentially Induces Inclusions in Multiple System Atrophy.
AB - Glial cytoplasmic inclusions (GCIs), commonly observed as alpha-synuclein (alpha
syn)-positive aggregates within oligodendrocytes, are the pathological hallmark
of multiple system atrophy. The origin of alpha-syn in GCIs is uncertain; there
is little evidence of endogenous alpha-syn expression in oligodendrocyte lineage
cells, oligodendrocyte precursor cells (OPCs), and mature oligodendrocytes
(OLGs). Here, based on in vitro analysis using primary rat cell cultures, we
elucidated that preformed fibrils (PFFs) generated from recombinant human alpha
syn trigger multimerization and an upsurge of endogenous alpha-syn in OPCs, which
is attributable to insufficient autophagic proteolysis. RNA-seq analysis of OPCs
revealed that alpha-syn PFFs interfered with the expression of proteins
associated with neuromodulation and myelination. Furthermore, we detected
cytoplasmic alpha-syn inclusions in OLGs through differentiation of OPCs pre
incubated with PFFs. Overall, our findings suggest the possibility of endogenous
alpha-syn accumulation in OPCs that contributes to GCI formation and perturbation
of neuronal/glial support in multiple system atrophy brains.
PMID- 29337116
TI - Impact of Swiprosin-1/Efhd2 on Adult Hippocampal Neurogenesis.
AB - Swiprosin-1/Efhd2 (Efhd2) is highly expressed in the CNS during development and
in the adult. EFHD2 is regulated by Ca2+ binding, stabilizes F-actin, and
promotes neurite extension. Previous studies indicated a dysregulation of EFHD2
in human Alzheimer's disease brains. We hypothesized a detrimental effect of
genetic ablation of Efhd2 on hippocampal integrity and specifically investigated
adult hippocampal neurogenesis. Efhd2 was expressed throughout adult neuronal
development and in mature neurons. We observed a severe reduction of the survival
of adult newborn neurons in Efhd2 knockouts, starting at the early neuroblast
stage. Spine formation and dendrite growth of newborn neurons were compromised in
full Efhd2 knockouts, but not upon cell-autonomous Efhd2 deletion. Together with
our finding of severe hippocampal tauopathy in Efhd2 knockout mice, these data
connect Efhd2 to impaired synaptic plasticity as present in Alzheimer's disease
and identify a role of Efhd2 in neuronal survival and synaptic integration in the
adult hippocampus.
PMID- 29337115
TI - Purification of GFRalpha1+ and GFRalpha1- Spermatogonial Stem Cells Reveals a
Niche-Dependent Mechanism for Fate Determination.
AB - Undifferentiated spermatogonia comprise a pool of stem cells and progenitor cells
that show heterogeneous expression of markers, including the cell surface
receptor GFRalpha1. Technical challenges in isolation of GFRalpha1+ versus
GFRalpha1- undifferentiated spermatogonia have precluded the comparative
molecular characterization of these subpopulations and their functional
evaluation as stem cells. Here, we develop a method to purify these
subpopulations by fluorescence-activated cell sorting and show that GFRalpha1+
and GFRalpha1- undifferentiated spermatogonia both demonstrate elevated
transplantation activity, while differing principally in receptor tyrosine kinase
signaling and cell cycle. We identify the cell surface molecule melanocyte cell
adhesion molecule (MCAM) as differentially expressed in these populations and
show that antibodies to MCAM allow isolation of highly enriched populations of
GFRalpha1+ and GFRalpha1- spermatogonia from adult, wild-type mice. In germ cell
culture, GFRalpha1- cells upregulate MCAM expression in response to glial cell
line-derived neurotrophic factor (GDNF)/fibroblast growth factor (FGF)
stimulation. In transplanted hosts, GFRalpha1- spermatogonia yield GFRalpha1+
spermatogonia and restore spermatogenesis, albeit at lower rates than their
GFRalpha1+ counterparts. Together, these data provide support for a model of a
stem cell pool in which the GFRalpha1+ and GFRalpha1- cells are closely related
but show key cell-intrinsic differences and can interconvert between the two
states based, in part, on access to niche factors.
PMID- 29337117
TI - XIST Derepression in Active X Chromosome Hinders Pig Somatic Cell Nuclear
Transfer.
AB - Pig cloning by somatic cell nuclear transfer (SCNT) remains extremely
inefficient, and many cloned embryos undergo abnormal development. Here, by
profiling transcriptome expression, we observed dysregulated chromosome-wide gene
expression in every chromosome and identified a considerable number of genes that
are aberrantly expressed in the abnormal cloned embryos. In particular, XIST, a
long non-coding RNA gene, showed high ectopic expression in abnormal embryos. We
also proved that nullification of the XIST gene in donor cells can normalize
aberrant gene expression in cloned embryos and enhance long-term development
capacity of the embryos. Furthermore, the increased quality of XIST-deficient
embryos was associated with the global H3K9me3 reduction. Injection of H3K9me
demethylase Kdm4A into NT embryos could improve the development of pre
implantation stage embryos. However, Kdm4A addition also induced XIST
derepression in the active X chromosome and thus was not able to enhance the in
vivo long-term developmental capacity of porcine NT embryos.
PMID- 29337118
TI - Recapitulation of Extracellular LAMININ Environment Maintains Stemness of
Satellite Cells In Vitro.
AB - Satellite cells function as precursor cells in mature skeletal muscle homeostasis
and regeneration. In healthy tissue, these cells are maintained in a state of
quiescence by a microenvironment formed by myofibers and basement membrane in
which LAMININs (LMs) form a major component. In the present study, we evaluated
the satellite cell microenvironment in vivo and found that these cells are
encapsulated by LMalpha2-5. We sought to recapitulate this satellite cell niche
in vitro by culturing satellite cells in the presence of recombinant LM-E8
fragments. We show that treatment with LM-E8 promotes proliferation of satellite
cells in an undifferentiated state, through reduced phosphorylation of JNK and
p38. On transplantation into injured muscle tissue, satellite cells cultured with
LM-E8 promoted the regeneration of skeletal muscle. These findings represent an
efficient method of culturing satellite cells for use in transplantation through
the recapitulation of the satellite cell niche using recombinant LM-E8 fragments.
PMID- 29337119
TI - SOX10 Single Transcription Factor-Based Fast and Efficient Generation of
Oligodendrocytes from Human Pluripotent Stem Cells.
AB - Scarce access to primary samples and lack of efficient protocols to generate
oligodendrocytes (OLs) from human pluripotent stem cells (hPSCs) are hampering
our understanding of OL biology and the development of novel therapies. Here, we
demonstrate that overexpression of the transcription factor SOX10 is sufficient
to generate surface antigen O4-positive (O4+) and myelin basic protein-positive
OLs from hPSCs in only 22 days, including from patients with multiple sclerosis
or amyotrophic lateral sclerosis. The SOX10-induced O4+ population resembles
primary human OLs at the transcriptome level and can myelinate neurons in vivo.
Using in vitro OL-neuron co-cultures, myelination of neurons by OLs can also be
demonstrated, which can be adapted to a high-throughput screening format to test
the response of pro-myelinating drugs. In conclusion, we provide an approach to
generate OLs in a very rapid and efficient manner, which can be used for disease
modeling, drug discovery efforts, and potentially for therapeutic OL
transplantation.
PMID- 29337121
TI - The Society of Thoracic Surgeons Congenital Heart Surgery Database: 2018 Update
on Outcomes and Quality.
AB - The Society of Thoracic Surgeons Congenital Heart Surgery Database is a
comprehensive registry of clinical outcomes that captures almost all pediatric
cardiac surgical operations in the United States. It is the platform for all
activities of The Society of Thoracic Surgeons related to the analysis of
outcomes and the improvement of quality in this subspecialty. This article
summarizes current aggregate national outcomes in congenital and pediatric
cardiac surgery and reviews related activities in the areas of quality
measurement, performance improvement, and transparency. The reported data about
aggregate national outcomes are exemplified by an analysis of 10 benchmark
operation groups performed from January 2013 through December 2016. This analysis
documents the overall aggregate Operative Mortality (interquartile range among
all participating programs) for the following procedural groups: off-bypass
coarctation repair, 1.3% (0.0% to 1.4%%); ventricular septal defect repair, 0.6%
(0.0% to 0.9%); tetralogy of Fallot repair, 1.1% (0.0% to 2.0%); complete
atrioventricular canal repair, 2.7% (0.0% to 4.4%); arterial switch operation,
2.2% (0.0% to 2.9%); arterial switch operation and ventricular septal defect
repair, 5.1% (0.0% to 8.3%); Glenn/HemiFontan, 2.1% (0.0% to 3.1%); Fontan
operation, 1.1% (0.0% to 0.0%); truncus arteriosus repair, 10.1% (0.0% to 15.4%);
and Norwood procedure, 15.8% (9.0% to 25.0%).
PMID- 29337120
TI - Deriving Dorsal Spinal Sensory Interneurons from Human Pluripotent Stem Cells.
AB - Cellular replacement therapies for neurological conditions use human embryonic
stem cell (hESC)- or induced pluripotent stem cell (hiPSC)-derived neurons to
replace damaged or diseased populations of neurons. For the spinal cord,
significant progress has been made generating the in-vitro-derived motor neurons
required to restore coordinated movement. However, there is as yet no protocol to
generate in-vitro-derived sensory interneurons (INs), which permit perception of
the environment. Here, we report on the development of a directed differentiation
protocol to derive sensory INs for both hESCs and hiPSCs. Two developmentally
relevant factors, retinoic acid in combination with bone morphogenetic protein 4,
can be used to generate three classes of sensory INs: the proprioceptive dI1s,
the dI2s, and mechanosensory dI3s. Critical to this protocol is the competence
state of the neural progenitors, which changes over time. This protocol will
facilitate developing cellular replacement therapies to reestablish sensory
connections in injured patients.
PMID- 29337122
TI - Lung Focused Resuscitation at a Specialized Donor Care Facility Improves Lung
Procurement Rates.
AB - BACKGROUND: Lung procurement for transplantation occurs in approximately 20% of
brain dead donors and is a major impediment to wider application of lung
transplantation. We investigated the effect of lung protective management at a
specialized donor care facility on lung procurement rates from brain dead donors.
METHODS: Our local organ procurement organization instituted a protocol of lung
protective management at a freestanding specialized donor care facility in 2008.
Brain dead donors from 2001 to 2007 (early period) were compared with those from
2009 to 2016 (current period) for lung procurement rates and other solid-organ
procurement rates using a prospectively maintained database. RESULTS: An overall
increase occurred in the number of brain dead donors during the study period
(early group, 791; late group, 1,333; p < 0.0001). The lung procurement rate
(lung donors/all brain dead donors) improved markedly after the introduction of
lung protective management (early group, 157 of 791 [19.8%]; current group, 452
of 1,333 [33.9%]; p < 0.0001). The overall organ procurement rate (total number
of organs procured/donor) also increased during the study period (early group,
3.5 organs/donor; current group, 3.8 organs/donor; p = 0.006). CONCLUSIONS: Lung
protective management in brain dead donors at a specialized donor care facility
is associated with higher lung utilization rates compared with conventional
management. This strategy does not adversely affect the utilization of other
organs in a multiorgan donor.
PMID- 29337123
TI - Mesenchymal Stem Cell-Based Therapy Improves Lower Limb Movement After Spinal
Cord Ischemia in Rats.
AB - BACKGROUND: Spinal cord ischemia is a devastating complication after thoracic and
thoracoabdominal aortic operations. In this study, we aimed to investigate the
effects of mesenchymal stem cells (MSCs), which have regenerative capability and
exert paracrine actions on damaged tissues, injected into rat models of spinal
cord ischemia-reperfusion injury. METHODS: Forty-five Sprague-Dawley rats were
divided into sham, phosphate-buffered saline (PBS), and MSC groups. Spinal cord
ischemia was induced in the latter two groups by balloon occlusion of the
thoracic aorta. MSCs and PBS were then immediately injected into the left carotid
artery of the MSC and PBS groups, respectively. Hindlimb motor function was
evaluated at 6 and 24 hours. The spinal cord was removed at 24 hours after
ischemia-reperfusion injury, and histologic and immunohistochemical analyses and
real-time polymerase chain reaction assessments were performed. RESULTS: Rats in
the MSC and PBS groups showed flaccid paraparesis/paraplegia postoperatively.
Hindlimb function was significantly better at 6 and 24 hours after ischemia
reperfusion injury in the MSC group than in the PBS group (p < 0.05). The number
of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive neuron
cells in the spinal cord and the ratio of Bax to Bcl2 were significantly larger
(p < 0.05) in the PBS group than in the MSC group. The injected MSCs were
observed in the spinal cord 24 hours after ischemia-reperfusion injury.
CONCLUSIONS: The MSC therapy by transarterial injection immediately after spinal
cord ischemia-reperfusion injury may improve lower limb function by preventing
apoptosis of neuron cells in the spinal cord.
PMID- 29337124
TI - Evaluation of Prophylactic Antibiotic Use for Delayed Sternal Closure After
Cardiothoracic Operation.
AB - BACKGROUND: Clinical practice guidelines provide recommendations for surgical
prophylaxis in patients undergoing cardiothoracic procedures. However, currently
no recommendations guide the management of antibiotic prophylaxis in patients who
require delayed sternal closure after cardiothoracic operation. METHODS: This is
a single-center, retrospective analysis. Data were extracted from The Society of
Thoracic Surgery database and electronic medical record from July 2011 through
January 2016. Patients included are adults (>=18 years old) after cardiothoracic
operation with delayed sternal closure. RESULTS: A total of 167 patients were
included for analysis. The majority of patients (131, 78.4%) were continued on
routine antibiotics and 36 patients (21.6%) were switched to broad-spectrum
antibiotics for prophylaxis. Of patients on routine antibiotic prophylaxis, 6
(4.6%) experienced a sternal surgical site infection, whereas 3 patients (8.3%)
switched to broad-spectrum agents before chest closure experienced a sternal
surgical site infection (p = 0.407). Eleven patients (6.6%) received an
abbreviated duration of antibiotics, 52 patients (31.1%) were continued on
antibiotics until the time of sternal closure, and 104 patients (62.3%) were
continued on antibiotics past the time of sternal closure. The incidence of
infection based on duration of prophylactic antibiotic was 0, 1 (1.9%), and 8
(7.7%), respectively (p = 0.352). CONCLUSIONS: Substantial variation was found in
the duration and selection of antibiotic prophylaxis for patients with delayed
sternal closure after cardiothoracic operation. Broad-spectrum antimicrobial
agents and extended durations of antibiotic prophylaxis were not associated with
benefits in the incidence of sternal wound infection and may increase the risk of
adverse effects.
PMID- 29337125
TI - Facilitating Hemostasis After Proximal Aortic Surgery: Results of The PROTECT
Trial.
AB - BACKGROUND: This study intended to evaluate the safety and hemostatic efficacy of
a novel vascular sealant (Tridyne; Neomend, Inc, Irvine, CA) compared with an
accepted adjunctive hemostatic agent applied to aortotomy and sutures lines in
cardiovascular operations. METHODS: Patients undergoing aortic valve replacement,
ascending aortic replacement, or aortic root replacement were randomly assigned
2:1 to Tridyne (n = 107) or Gelfoam Plus (Baxter Healthcare Corp, Hayward, CA) (n
= 51). These groups were similar with regard to age, sex, race, medical history,
duration of bypass and cross-clamping, and number of suture lines treated. Suture
lines were treated after confirmation of some leakage but before formal removal
of the clamp. RESULTS: The median bleeding time was significantly lower for
Tridyne versus Gelfoam Plus (0 versus 10.0 minutes, p < 0.0001). Immediate
hemostasis was achieved in 59.4% of the Tridyne group versus 16.0% of Gelfoam
Plus group (p < 0.0001). A significantly greater proportion of patients in the
Tridyne group achieved successful hemostasis at the aortic suture line than
patients in the Gelfoam Plus group (85.7% versus 40.0%, p < 0.0001). The Clinical
Events Committee adjudicated 7 patients with possible device-related serious
adverse events: 3 patients (2.9%) in the Tridyne group and 4 patients (8.2%) in
the Gelfoam Plus group (p = 0.2097). CONCLUSIONS: Tridyne was safe and effective
when used as an adjunct to conventional hemostasis to treat high-pressure vessels
in patients who receive anticoagulation agents, in reducing time to hemostasis,
and in promoting both immediate and persistent hemostasis.
PMID- 29337126
TI - Rigid Plate Fixation Versus Wire Cerclage: Patient-Reported and Economic Outcomes
From a Randomized Trial.
AB - BACKGROUND: In a multicenter randomized trial, sternal closure after cardiac
operations using rigid plate fixation (RPF) compared with wire cerclage (WC)
resulted in improved sternal healing, reduced sternal complications, and was cost
neutral at 6 months. Additional secondary end points are presented from this
trial. METHODS: Twelve United States centers randomized 236 patients to RPF (n =
116) or WC (n = 120). Patient-reported outcomes measures, including pain,
function, and quality of life scores, were assessed through 6 months and
correlated to computed tomography-derived sternal healing scores using logistic
regression. Cost analysis through 90 days was performed to mimic bundled care
models. RESULTS: All patient-reported outcomes measures were numerically better
in RPF patients than in WC patients at all assessments. RPF resulted in more
patients reporting no sternal pain after coughing at 3 weeks (41.1% vs 19.6%; p =
0.001) and 6 weeks (54.5% vs 35.1%; p = 0.005) and at rest at 6 weeks (74.1% vs
58.8%; p = 0.02) and 3 months (87.6% vs 75.9%; p = 0.03) compared with WC. Better
sternal healing scores correlated to having no sternal pain at rest (odds ratio,
1.6; 95% confidence interval, 1.2 to 2.2; p = 0.002) and after coughing (odds
ratio, 1.6; 95% confidence interval, 1.2 to 2.2; p = 0.0007). RPF resulted in
improvements in the 36-Item Short Form Health Survey quality of life scores at 3
weeks (53.5 +/- 8.7 vs 50.5 +/- 10.4; p = 0.03), 6 weeks (45.3 +/- 8.4 vs 42.7 +/
8.4; p = 0.03), and 6 months (56.4 +/- 6.8 vs 53.9 +/- 9.0; p = 0.04) compared
with WC. Through 90 days, RPF compared with WC was $1,888 less (95% confidence
interval, -$8,889 to $4,273; p = 0.52). CONCLUSIONS: In patients undergoing
sternal closure after median sternotomy, RPF compared with WC resulted in reduced
sternal pain, improved upper extremity function, and similar total 90-day costs.
PMID- 29337127
TI - [Epidemiology of emergency consultations for acute urine retention].
AB - INTRODUCTION: Acute urinary retention (AUR) is a common reason for emergency
consultation. It may be spontaneous or precipitated and affects both men and
women. The purpose of this study was to determine the profile of men visiting
emergency departments for an AUR. MATERIEL AND METHODS: A retrospective
monocentric study including all men who consulted the emergency department
between January 2014 and December 2016 for AUR was conducted. RESULTS: In 3
years, 731 patients were admitted for AUR (611 men and 120 women). The mean age
was 71.6+/-14 years with a mean retention volume of 948+/-668mL drained for 96%
of patients (n=584) through a bladder catheter and 4% (n=27) with a suprapubic
catheter. Most patients had an urological (66%, n=104) or neurologic (40%, n=242)
history and 23% (n=136) already had an episode of AUR. In 28% of cases (n=173),
the globe was not painful. A majority of AUR were spontaneous, 53% (n=326) versus
46% (n=279) who were precipitated, secondary to a recent surgical procedure (<1
month) (15%, n=89), hematuria (9%, n=54), or male urinary tract infections (7%,
n=42). Patients were treated externally in 71% (n=436), 25% (n=153) were
hospitalized with significantly more comorbidities. CONCLUSION: Men consulting
emergency for AUR are 72 years old, with a globe volume of 942mL. Thirty-three
percent have a history of BPH, with a prostate treatment like alpha-blockers
type. Almost all patients were treated with a bladder catheter and the majority
was treated externally. LEVEL OF EVIDENCE: 4.
PMID- 29337128
TI - [Estimating minimum period of time to perform prostate MRI after prostate biopsy:
Clinical and histological bleeding risk factors; from a prospective study].
AB - : A minimum delay of 4 to 6 weeks between biopsy and multiparametric prostatic
MRI (mpMRI) is admitted due to post-biopsy hemorrhage that can impact MRI reading
without strong scientific evidence. The objective of the study was to evaluate
the best period between prostate biopsy and 3Tesla mpMRI and searching for
predictive factors of intraprostatic blood. METHOD: A prostate biopsy followed by
a 4-week prostate MRI (MRIp M1) was performed. In case of hemorrhage, MRI was
rescheduled at 8 and 12 weeks (M2/M3). We analyzed the persistant bleeding to
identify risk factors: anticoagulant/antiaggregant, post-biopsy side effects,
histological criteria. RESULTS: In this prospective, single-center study, we
included 40 patients followed for suspected prostate cancer between December 2014
and March 2016. At the MRIpM1, blood was found for 97.5 % of the patients. The
rates were 90.9 % and 88.9 % respectively at the M2 and M3 mpMRI. Compared to
initial blood volume on MRIpM1, a significant decrease in blood volume was
observed between M1 and M2 (55 %; P=0.0091). We showed a 75 % decrease between M1
and M3 (P=0.0003). Low urinary tract symptoms (LUTS) suggesting urinary infection
at 4 weeks were significantly correlated with blood volume on MRIpM1 (P=0.0063).
The blood volume was higher in case of unconformity between biopsy and mpMRI
results for detection of significant tumors (11.3 vs. 2.3; P=0.0051).
CONCLUSIONS: A minimum of 8-week biopsy and mpMRI period would limit post-biopsy
hemorrhage, predicted by LUTS suggesting urinary infection. A delay of 12 weeks
would be optimal without delaying the management of the patient. LEVEL OF
EVIDENCE: 4.
PMID- 29337129
TI - Effect of amino acid substitution of CAPRICE on cell-to-cell movement ability in
Arabidopsis root epidermis.
AB - An R3-type MYB transcription factor, CAPRICE (CPC), is known to promote root hair
cell differentiation in Arabidopsis root epidermis. The CPC protein moves from
non-hair cells to the neighboring cells, and acts as an inducer of root hair
formation. In contrast, we previously showed that the CPC homolog, ENHANCER OF
TRY AND CPC1 (ETC1), does not move between the root epidermal cells. To clarify
the critical difference in the cell-to-cell movement ability of CPC and ETC1
proteins, we generated five different chimeras of CPC and ETC1. As expected, four
of the five chimeric proteins with substitution of CPC amino acids with those of
ETC1 induced many root hair and no-trichome phenotype, like CPC. These chimeric
proteins essentially maintained the cell-to-cell movement ability of CPC.
However, one chimeric protein in which ETC1 was sandwiched between the CPC
specific movement motifs of S1 and S2 did not induce ectopic root hair formation.
This chimeric protein did not move between the cells. These results indicate that
the maintenance of not only the S1 and S2 motifs but also the precise structure
of CPC protein might be necessary for the cell-to-cell movement of CPC. Our
results should help in further unraveling of the roles of these MYB transcription
factors in root hair formation.
PMID- 29337130
TI - An organizing role for the TGF-beta signaling pathway in axes formation of the
annelid Capitella teleta.
AB - Embryonic organizers are signaling centers that coordinate developmental events
within an embryo. Localized to either an individual cell or group of cells,
embryonic organizing activity induces the specification of other cells in the
embryo and can influence formation of body axes. In the spiralian Capitella
teleta, previous cell deletion studies have shown that organizing activity is
localized to a single cell, 2d, and this cell induces the formation of the dorsal
ventral axis and bilateral symmetry. In this study, we attempt to identify the
signaling pathway responsible for the organizing activity of 2d. Embryos at
stages when organizing activity is occurring were exposed to various small
molecule inhibitors that selectively inhibited either the Activin/Nodal or the
BMP branch of the TGF-beta signaling pathway. Embryos were then raised to larval
stages, and scored for axial anomalies analogous to 2d ablated phenotypes. Our
results show that interference with the Activin/Nodal pathway through a short
three hour exposure to the inhibitor SB431542 results in larvae that lack
bilateral symmetry and a detectable dorsal-ventral axis. However, interference
with the BMP signaling pathway through exposure to the inhibitors DMH1 and
dorsomorphin dihydrochloride does not appear to play a role in specification by
2d of the dorsal-ventral axis or bilateral symmetry. Our findings highlight
species differences in how the molecular architecture of the conserved TGF-beta
superfamily signaling pathway components was utilized to mediate the organizing
activity signal during early spiralian development.
PMID- 29337131
TI - Modelling non-Markovian fluctuations in intracellular biomolecular transport.
AB - To model non-Markovian fluctuations arising in biomolecular transport, we
introduce a stochastic process with memory where Brownian motion is modulated
sinusoidally. The probability density function and moments of this non-Markovian
process are evaluated analytically as Hida stochastic functional integrals.
Comparison of graphs of computed variance vis-a-vis empirical data for protein
diffusion coefficients closely match with both exhibiting emergent superdiffusive
then subdiffusive behavior for longer proteins.
PMID- 29337132
TI - Understanding pivotal experiences in behavior change for the design of
technologies for personal wellbeing.
AB - Most health technologies are designed to support people who have already decided
to work toward better health. Thus, there remains an opportunity to design
technologies to help motivate people who have not yet decided to make a change.
Understanding the experiences of people who have already started to make a health
behavior change and how they made a pivotal decision can be useful in
understanding how to design such tools. In this paper, we describe results from
data collected in 2 phases. Phase 1 consisted of 127 surveys and 13 interviews
with adults who have already accomplished behavior change(s). Phase 2 consisted
of 117 surveys and 12 interviews with adults who have either already accomplished
their behavior change(s) or are currently working toward them. We identified four
factors that lead to pivotal experiences: (1) prolonged discontent and desire to
change, (2) significant changes that increase fear or hope of future, (3)
increased understanding of one's behavior and personal data, and (4) social
accountability. We also describe a design space for designing technology-based
interventions for encouraging people to decide to make a change to improve their
health. Based on feedback from participants, we discuss opportunities for further
exploration of the design space for people who are not yet motivated to change
and for ethical considerations for this type of intervention.
PMID- 29337133
TI - Cathodal tDCS of the bilateral anterior temporal lobes facilitates semantically
driven verbal fluency.
AB - In a verbal fluency task, a person is required to produce as many exemplars of a
given category (e.g., 'animals', or words starting with 'f') as possible within a
fixed duration. Successful verbal fluency performance relies both on the depth of
search within semantic/phonological neighborhoods ('clustering') and the ability
to flexibly disengage between exhausted clusters ('switching'). Convergent
evidence from functional imaging and neuropsychology suggests that cluster-switch
behaviors engage dissociable brain regions. Switching has been linked to a
frontoparietal network dedicated to executive functioning and controlled lexical
retrieval, whereas clustering is more commonly associated with temporal lobe
regions dedicated to semantic and phonological processing. Here we attempted to
modulate cluster-switch dynamics among neurotypical adults (N = 24) using
transcranial direct current stimulation (tDCS) delivered at three sites: a)
anterior temporal cortex; b) frontal cortex; and c) temporoparietal cortex.
Participants completed letter-guided and semantic category verbal fluency tasks
pre/post stimulation. Cathodal stimulation of anterior temporal cortex
facilitated the total number of words generated and the number of words generated
within clusters during semantic category verbal fluency. These neuromodulatory
effects were specific to stimulation of the one anatomical site. Our findings
highlight the role of the anterior temporal lobes in representing semantic
category structure and support the claim that clustering and switching behaviors
have distinct substrates. We discuss implications both for theory and application
to neurorehabilitation.
PMID- 29337134
TI - Acetylcholine Receptor Antibody Titers and Clinical Course after Influenza
Vaccination in Patients with Myasthenia Gravis: A Double-Blind Randomized
Controlled Trial (ProPATIent-Trial).
AB - BACKGROUND: It is a continuous matter of discussion whether immune activation by
vaccination in general and Influenza vaccination in particular increases the risk
for clinical deterioration of autoimmune diseases. This prospective study
investigated the serological and clinical course of autoimmune Myasthenia gravis
(MG) after a seasonal influenza vaccination. METHODS: This randomized, placebo
controlled, double-blind study enrolled MG patients with antibodies against
acetylcholine-receptors (AChR-ab). They were allocated to receive seasonal
influenza vaccine or placebo. The primary endpoint was the relative change of
AChR-ab-titer over 12weeks. A relative increase of 20% was set as non-inferiority
margin. Secondary endpoints were clinical changes in the modified Quantitative
Myasthenia Gravis Score (QMG), increase of anti-influenza-ELISA-antibodies, and
changes of treatment. The study is registered with Clinicaltrialsregister.eu,
EudraCT number 2006-004374-27. FINDINGS: 62 patients were included. Mean+/
standard deviation (median) in the vaccine and placebo group were AChR-ab-titer
changes of -6.0%+/-23.3% (-4.0%) and -2.8%+/-22.0% (-0.5%) and QMG score changes
of -0.08+/-0.27 (0.17) and 0.11+/-0.31 (0.00), respectively. The difference
between groups (Hodges-Lehmann estimate with 95% CI) was - for the AChR-ab-titer
change 4.0% [-13.3%, 4.5%] (p=0.28 for testing a difference, p<0.0001 for testing
non-inferiority) and for the QMG change 0.00 [-0.17, 0.00] (p=0.79 for testing a
difference). The occurrence of 74 adverse events (AE) was comparable between
groups. The most common AE was flu-like symptoms. One serious AE (hospitalisation
following gastrointestinal haemorrhage) in the verum group was not related to the
vaccine. INTERPRETATION: Influenza vaccination in MG is safe. Uprating the
potential risk of a severe course of MG exacerbation during influenza infection
compared to the 95% CI differences for the endpoints, vaccination is principally
indicated in this patient population.
PMID- 29337135
TI - Defining Bedaquiline Susceptibility, Resistance, Cross-Resistance and Associated
Genetic Determinants: A Retrospective Cohort Study.
AB - BACKGROUND: Bedaquiline (BDQ) is a novel agent approved for use in combination
treatment of multi-drug resistant tuberculosis (MDR-TB). We sought to determine
BDQ epidemiological cut-off values (ECVs), define and assess interpretive
criteria against putative resistance associated variants (RAVs), microbiological
outcomes and cross resistance with clofazimine (CFZ). METHODS: A retrospective
cohort study was conducted. Minimal inhibitory concentrations (MIC) to BDQ were
determined using 7H9 broth microdilution (BMD) and MGIT960. RAVs were genetically
characterised using whole genome sequencing. BDQ ECVs were determined using
ECOFFinder and compared with 6-month culture conversion status and CFZ MICs.
FINDINGS: A total of 391 isolates were analysed. Susceptible and intermediate
categories were determined to have MICs of <=0.125MUg/ml and 0.25MUg/ml using BMD
and <=1MUg/ml and 2MUg/ml using MGIT960 respectively. Microbiological failures
occurred among BDQ exposed patients with a non-susceptible BDQ MIC, an Rv0678
mutation and <=2 active drug classes. The Rv0678 RAVs were not the dominant
mechanism of CFZ resistance and cross resistance was limited to isolates with an
Rv0678 mutation. INTERPRETATION: Criteria for BDQ susceptibility are defined and
will facilitate improved early detection of resistance. Cross- resistance between
BDQ and CFZ is an emerging concern but in this study was primarily among those
with an Rv0678 mutation.
PMID- 29337136
TI - As Extracellular Glutamine Levels Decline, Asparagine Becomes an Essential Amino
Acid.
AB - When mammalian cells are deprived of glutamine, exogenous asparagine rescues cell
survival and growth. Here we report that this rescue results from use of
asparagine in protein synthesis. All mammalian cell lines tested lacked cytosolic
asparaginase activity and could not utilize asparagine to produce other amino
acids or biosynthetic intermediates. Instead, most glutamine-deprived cell lines
are capable of sufficient glutamine synthesis to maintain essential amino acid
uptake and production of glutamine-dependent biosynthetic precursors, with the
exception of asparagine. While experimental introduction of cytosolic
asparaginase could enhance the synthesis of glutamine and increase tricarboxylic
acid cycle anaplerosis and the synthesis of nucleotide precursors, cytosolic
asparaginase suppressed the growth and survival of cells in glutamine-depleted
medium in vitro and severely compromised the in vivo growth of tumor xenografts.
These results suggest that the lack of asparaginase activity represents an
evolutionary adaptation to allow mammalian cells to survive pathophysiologic
variations in extracellular glutamine.
PMID- 29337138
TI - Let-7 Suppresses B Cell Activation through Restricting the Availability of
Necessary Nutrients.
AB - The control of uptake and utilization of necessary extracellular nutrients
glucose and glutamine-is an important aspect of B cell activation. Let-7 is a
family of microRNAs known to be involved in metabolic control. Here, we employed
several engineered mouse models, including B cell-specific overexpression of
Lin28a or the let-7a-1/let-7d/let-7f-1 cluster (let-7adf) and knockout of
individual let-7 clusters to show that let-7adf specifically inhibits T cell
independent (TI) antigen-induced immunoglobulin (Ig)M antibody production. Both
overexpression and deletion of let-7 in this cluster leads to altered TI-IgM
production. Mechanistically, let-7adf suppresses the acquisition and utilization
of key nutrients, including glucose and glutamine, through directly targeting
hexokinase 2 (Hk2) and by repressing a glutamine transporter Slc1a5 and a key
degradation enzyme, glutaminase (Gls), a mechanism mediated by regulation of c
Myc. Our results suggest a novel role of let-7adf as a "metabolic brake" on B
cell antibody production.
PMID- 29337137
TI - Basal Mitophagy Occurs Independently of PINK1 in Mouse Tissues of High Metabolic
Demand.
AB - Dysregulated mitophagy has been linked to Parkinson's disease (PD) due to the
role of PTEN-induced kinase 1 (PINK1) in mediating depolarization-induced
mitophagy in vitro. Elegant mouse reporters have revealed the pervasive nature of
basal mitophagy in vivo, yet the role of PINK1 and tissue metabolic context
remains unknown. Using mito-QC, we investigated the contribution of PINK1 to
mitophagy in metabolically active tissues. We observed a high degree of mitophagy
in neural cells, including PD-relevant mesencephalic dopaminergic neurons and
microglia. In all tissues apart from pancreatic islets, loss of Pink1 did not
influence basal mitophagy, despite disrupting depolarization-induced Parkin
activation. Our findings provide the first in vivo evidence that PINK1 is
detectable at basal levels and that basal mammalian mitophagy occurs
independently of PINK1. This suggests multiple, yet-to-be-discovered pathways
orchestrating mammalian mitochondrial integrity in a context-dependent fashion,
and this has profound implications for our molecular understanding of vertebrate
mitophagy.
PMID- 29337139
TI - Identification of yellow gene family in Agrotis ipsilon and functional analysis
of Aiyellow-y by CRISPR/Cas9.
AB - The yellow gene family has been identified in several model insects, but yellow
genes were poorly identified in non-model insects and the functions of yellow
genes are largely unknown. In this study, we identified seven yellow genes in an
important agricultural pest Agrotis ipsilon. Each gene encodes a protein
containing a major royal jelly domain. Phylogenetic analysis defined these genes
as yellow-y, -b, -b2, -c, -d, -e, and -h, respectively. The A. ipsilon yellow
genes yellow-b, -b2, and -c were stably expressed in all developmental stages and
tissues analyzed, whereas the other four yellow genes had unique expression
patterns, suggesting distinct physiological roles of each gene. Using the
CRISPR/Cas9 system, we successfully disrupted yellow-y in A. ipsilon and obtained
G0 insects with somatic mutations. Unlike the black of wild-type newly hatched
larvae and of adults, the mutants were yellow, although in the pupal stage mutant
coloration did not differ from wild-type coloration. This phenotype was inherited
by G1 offspring. The G0 mutants did not show any growth deficiency compared with
control insects; however, a dehydration-like phenotype was observed in newly
hatched G1 larvae from sibling crossed mutants. Our results indicate that A.
ipsilon yellow-y gene plays a role in body pigmentation and also might function
in waterproofing.
PMID- 29337140
TI - Characteristics and Prognostic Factors for Patients With HER2-overexpressing
Breast Cancer and Brain Metastases in the Era of HER2-targeted Therapy: An
Argument for Earlier Detection.
AB - BACKGROUND: Although brain metastases (BM) are associated with poor prognosis,
patients with human epidermal growth factor receptor 2 (HER2) overexpressing
(HER2+) breast cancer (BC) with BM who are treated with anti-HER2 therapy have a
relatively longer survival after BM diagnosis compared with other subtypes and
HER2+ patients previously untreated with anti-HER2 therapy. It is unclear if
previously reported prognostic factors are applicable to patients with HER2+ BC
in the era of HER2-targeted therapy. PATIENTS AND METHODS: We evaluated 100
consecutive patients with HER2+ BC with BM who underwent radiation therapy as
primary BM treatment from January 2001 to December 2011 at Memorial Sloan
Kettering Cancer Center by retrospective review. Patient characteristics at the
time of BM diagnosis and their associations with time from BM to death were
evaluated by Kaplan-Meier curves, log-rank tests, and Cox proportional hazard
models. RESULTS: Significantly better survival from BM was noted for patients
with higher performance status, fewer BM lesions, continued use of HER2-targeted
therapy after BM diagnosis, and better controlled extracranial metastatic
disease. Absence of neurologic symptoms at BM diagnosis was significantly
associated with fewer lesions, decreased use of whole brain radiotherapy, and
longer survival in univariate and multivariate analysis (multivariate hazard
ratio, 3.69; 95% confidence interval, 1.69-8.07). CONCLUSION: Our finding
supports the continued use of HER2-targeted therapy after BM diagnosis. In
addition, future research on the clinical impact of detecting asymptomatic BM in
patients with HER2+ BC, in terms of improving prognosis, quality of life, and
avoidance of whole brain radiotherapy, is warranted.
PMID- 29337141
TI - Alterations of oxygen consumption and extracellular acidification rates by
glutamine in PBMCs of SLE patients.
AB - We evaluated plasma glutamine levels and basal mitochondrial oxygen consumption
rate (mOCRB) and basal extracellular acidification rate (ECARB) of peripheral
blood mononuclear cells (PBMCs) of systemic lupus erythematous (SLE) patients and
healthy controls (HCs). Lower plasma glutamine levels correlated with higher SLE
disease activity indexes (p=0.025). Incubated in DMEM containing 100mg/dL
glucose, SLE-PBMCs displayed lower mOCRB (p=0.018) but similar ECARB (p=0.467) to
those of HC-PBMCs, and their mOCRB got elevated (p<0.001) without altering ECARB
(p=0.239) by supplementation with 2 or 4mM glutamine. We conclude that impaired
mitochondrial respiration of SLE-PBMCs could be improved by glutamine under
euglycemic condition.
PMID- 29337143
TI - The role of Hedgehog-responsive fibroblasts in facial nerve regeneration.
AB - BACKGROUND: Facial nerve paralysis is a significant cause of morbidity, affecting
facial appearance, emotional expression, speech, oral competence, and vision. A
more complete understanding of the complex cellular events required for
successful nerve regeneration may reveal new therapeutic targets. The role of
fibroblasts in regeneration, and the process by which the nerve reforms its three
dimensional structure after a transection injury, are not fully understood. The
Hedgehog signaling pathway has been shown to mediate nerve sheath formation
during development. We therefore sought to characterize the role of Hedgehog
responsive cells following transection of the facial nerve. METHODS: Two
transgenic mouse lines with reporters for the downstream effector of Hedgehog
signaling, Gli1, were used. The animals underwent a unilateral facial nerve
transection injury, and the contralateral side served as a control. Facial nerves
were analyzed via immunohistochemistry and immunofluorescence at predetermined
time points as the facial nerve regenerated after the transection injury.
RESULTS: There was a statistically significant increase in Gli1+ cells both at
the site of injury and within the distal nerve segment over time. Gli1+ cells are
fibroblasts within the nerve and appear to contribute to the reformation of the
nerve sheath after injury. CONCLUSION: These findings describe a key signaling
pathway by which fibroblasts participate in motor nerve regeneration. Fibroblasts
that reside within the nerve respond to injury and may represent a novel
therapeutic target in the context of facial nerve regeneration after transection
injury.
PMID- 29337144
TI - Early activation of Egr-1 promotes neuroinflammation and dopaminergic
neurodegeneration in an experimental model of Parkinson's disease.
AB - The progressive loss of dopaminergic neurons in the substantia nigra pars
compacta (SNpc) is one of the hallmarks of Parkinson's disease (PD).
Neuroinflammation has been proposed to contributes to the progressive nature of
the disease. Early growth response-1 (Egr-1), a zinc finger transcription factor,
has been shown to have a crucial role in both neuronal death and the inflammatory
response. However, whether and how Egr-1 is involved in the pathogenesis of PD
has not been investigated. Using the subacute 1-methyl-4-phenyl-1,2,3,6
tetrahydropyridine (MPTP) mouse model of PD, we identified early peak induction
of Egr-1 in the SNpc but not in the striatum. In situ immunofluorescent analysis
showed that Egr-1 predominantly locates in the nuclei of nigral AldoC (+)
astrocytes upon MPTP treatment. Genetic ablation of Egr-1 or inhibition of its
transcriptional activity by Mithramycin A significantly suppresses the activation
of both astrocytes and microglia, decreases proinflammatory cytokine expression,
and protects dopaminergic cell bodies from degeneration in the SNpc. Taken
together, these findings demonstrate that the induction of Egr-1 promotes
neuroinflammation and dopaminergic cell body loss in the SNpc of MPTP-induced
mouse model, suggesting an important role of astrocytic Egr-1 in
neuroinflammation in PD.
PMID- 29337142
TI - Express: A database of transcriptome profiles encompassing known and novel
transcripts across multiple development stages in eye tissues.
AB - Advances in sequencing have facilitated nucleotide-resolution genome-wide
transcriptomic profiles across multiple mouse eye tissues. However, these RNA
sequencing (RNA-seq) based eye developmental transcriptomes are not organized for
easy public access, making any further analysis challenging. Here, we present a
new database "Express" (http://www.iupui.edu/~sysbio/express/) that unifies
various mouse lens and retina RNA-seq data and provides user-friendly
visualization of the transcriptome to facilitate gene discovery in the eye. We
obtained RNA-seq data encompassing 7 developmental stages of lens in addition to
that on isolated lens epithelial and fibers, as well as on 11 developmental
stages of retina/isolated retinal rod photoreceptor cells from publicly available
wild-type mouse datasets. These datasets were pre-processed, aligned, quantified
and normalized for expression levels of known and novel transcripts using a
unified expression quantification framework. Express provides heatmap and browser
view allowing easy navigation of the genomic organization of transcripts or gene
loci. Further, it allows users to search candidate genes and export both the
visualizations and the embedded data to facilitate downstream analysis. We
identified total of >81,000 transcripts in the lens and >178,000 transcripts in
the retina across all the included developmental stages. This analysis revealed
that a significant number of the retina-expressed transcripts are novel.
Expression of several transcripts in the lens and retina across multiple
developmental stages was independently validated by RT-qPCR for established genes
such as Pax6 and Lhx2 as well as for new candidates such as Elavl4, Rbm5, Pabpc1,
Tia1 and Tubb2b. Thus, Express serves as an effective portal for analyzing pruned
RNA-seq expression datasets presently collected for the lens and retina. It will
allow a wild-type context for the detailed analysis of targeted gene-knockout
mouse ocular defect models and facilitate the prioritization of candidate genes
from Exome-seq data of eye disease patients.
PMID- 29337145
TI - Interaction of DCF1 with ATP1B1 induces impairment in astrocyte structural
plasticity via the P38 signaling pathway.
AB - Astrocytes are known to regulate and support neuronal and synaptic functions.
Changes in their size and morphology in mouse models result in mental
retardation. However, the mechanism underlying these morphological changes
remains unclear. In the present study, abnormal astrocyte morphology was found in
the mouse brain following knockout of dendritic cell factor 1 (Dcf1).
Immunoprecipitation-mass spectrometry (IP-Mass) identified that ATP1B1 is bound
to DCF1, and co-immunoprecipitation and cell fluorescence further confirmed an
interaction between these two proteins, with asparagine residue 266 of ATP1B1
being required for the interaction with DCF1. Moreover, Dcf1 knockout in mice
resulted in upregulation of ATP1B1 expression in the hippocampus. Furthermore,
DCF1 interaction with ATP1B1 in astrocytes impaired their structural plasticity.
Ultimately, Dcf1 knockout increased glutamate release. Mechanism exploration
proposed that Dcf1 knockout led to significantly perturbed expression of AMPA
receptors (AMPARs) and induced morphological changes in astrocytes through the
P38 signaling pathway. Our data shed light on the possible mechanisms underlying
changes in astrocyte morphology and provide new avenues for the exploration of
proteins involved in glutamate release.
PMID- 29337146
TI - Apelin-13 attenuates ER stress-mediated neuronal apoptosis by activating
Galphai/Galphaq-CK2 signaling in ischemic stroke.
AB - Cerebral ischemia/reperfusion (I/R) injury-induced neuronal apoptosis contributes
to the death and disability in patients with ischemic stroke. However, underlying
mechanisms remain elusive and it lacks effective treatment. Here we reported that
the expression of casein kinase 2 (CK2) was significantly reduced in brains of
middle cerebral artery occlusion/reperfusion (MACO/R) model rats and oxygen
glucose deprivation/reperfusion (OGD/R) model neurons, which was associated with
the activation of eIF2-ATF4-CHOP signaling pathway, leading to neuronal
apoptosis. Moreover, we found that apelin-13 significantly upregulated CK2
expression and inhibited eIF2-ATF4-CHOP activation, attenuating cerebral I/R
injury-induced infarct and neuronal apoptosis in MACO/R model rats and OGD/R
model neurons. Furthermore, we demonstrated that the rescue effect of apelin-13
on I/R injury-induced neuronal apoptosis was mediated by Galphai/Galphaq-CK2
dependent inhibition of eIF2-ATF4-CHOP activation. These data indicated cerebral
I/R injury reduced CK2 expression and activated eIF2-ATF4-CHOP signaling
contributing to neuronal apoptosis, and apelin-13 can activate Galphai/Galphaq
CK2 signaling attenuating eIF2-ATF4-CHOP-mediated neuronal apoptosis. It provides
a novel insight that not only apelin-13 but also CK2 agonists may have
therapeutic potential for protecting neurons from I/R injury-induced apoptosis,
facilitating post-stroke recovery.
PMID- 29337147
TI - Neuronal PTEN deletion in adult cortical neurons triggers progressive growth of
cell bodies, dendrites, and axons.
AB - Deletion of the phosphatase and tensin (PTEN) gene in neonatal mice leads to
enlargement of the cell bodies of cortical motoneurons (CMNs) in adulthood
(Gutilla et al., 2016). Here, we assessed whether PTEN deletion in adult mice
would trigger growth of mature neurons. PTEN was deleted by injecting AAV-Cre
into the sensorimotor cortex of adult transgenic mice with a lox-P flanked exon 5
of the PTEN gene and Cre-dependent reporter gene tdTomato. PTEN-deleted CMN's
identified by tdT expression and retrograde labeling with fluorogold (FG) were
significantly enlarged four months following PTEN deletion, and continued to
increase in size through the latest time intervals examined (12-15 months post
deletion). Sholl analyses of tdT-positive pyramidal neurons revealed increases in
dendritic branches at 6 months following adult PTEN deletion, and greater
increases at 12 months. 12 months after adult PTEN deletion, axons in the
medullary pyramids were significantly larger and G-ratios were higher. Mice with
PTEN deletion exhibited no overt neurological symptoms and no seizures.
Assessment of motor function on the rotarod and cylinder test revealed slight
impairment of coordination with unilateral deletion; however, mice with bilateral
PTEN deletion in the motor cortex performed better than controls on the rotarod
at 8 and 10 months post-deletion. Our findings demonstrate that robust neuronal
growth can be induced in fully mature cortical neurons long after the
developmental period has ended and that this continuous growth occurs without
obvious functional impairments.
PMID- 29337148
TI - And Now, Death by Proton Pump Inhibitor?
PMID- 29337149
TI - Just the FRAX: Management of Glucocorticoid-Induced Osteoporosis.
PMID- 29337150
TI - Heptose 1,7-Bisphosphate Directed TIFA Oligomerization: A Novel PAMP-Recognizing
Signaling Platform in the Control of Bacterial Infections.
PMID- 29337151
TI - Development of the Enteric Nervous System: A Genetic Guide to the Perplexed.
PMID- 29337152
TI - How to Obtain Training in Nutrition During the Gastroenterology Fellowship.
PMID- 29337153
TI - Pancreatitis: A Tale of Two Proteases.
PMID- 29337154
TI - Intraductal Papillary Mucinous Neoplasm as the Focus for Early Detection of
Pancreatic Cancer.
PMID- 29337155
TI - NVR 3-778 Plus Pegylated Interferon-alpha Treatment for Chronic Hepatitis B Viral
Infections: Could 1 + 1 = 3?
PMID- 29337156
TI - Nonceliac Gluten Sensitivity: What Is the Culprit?
PMID- 29337157
TI - Update on the Use of Vonoprazan: A Competitive Acid Blocker.
PMID- 29337159
TI - Colonoscopy Risks: What Is Known and What Are the Next Steps?
PMID- 29337160
TI - Response to "XPA is primarily cytoplasmic but is transported into the nucleus
upon UV damage".
PMID- 29337161
TI - Cellular redox, cancer and human papillomavirus.
AB - High-risk Human Papillomavirus (HR-HPV) is the causative agent of different human
cancers. A persistent HR-HPV infection alters several cellular processes involved
in cell proliferation, apoptosis, immune evasion, genomic instability and
transformation. Cumulative evidence from past studies indicates that HR-HPV
proteins are associated with oxidative stress (OS) and has been proposed as a
risk factor for cancer development. Reactive oxygen and nitrogen species (RONS)
regulate a plethora of processes inducing cellular proliferation, differentiation
and death. Oxidative stress (OS) is generated when an imbalance in the redox
state occurs due to deregulation of the oxidant and antioxidant systems, which,
in turn, promotes the damage of DNA, proteins and lipids, allowing the
accumulation of mutations and genome instability. OS has been associated with the
establishment and development of different cancers, and it has recently been
proposed as a co-factor in cervical cancer development. This review is focused on
evidence regarding the association of OS with HR-HPV proteins, and the interplay
of the viral proteins with different elements of the antioxidant and DNA damage
response (DDR) systems, emphasizing the processes that might be required for the
viral life cycle and viral DNA integration into the host genome, which is a key
element in the carcinogenic process induced by HR-HPV.
PMID- 29337162
TI - Antiviral activity of K22 against members of the order Nidovirales.
AB - Recently, a novel antiviral compound (K22) that inhibits replication of a broad
range of animal and human coronaviruses was reported to interfere with viral RNA
synthesis by impairing double-membrane vesicle (DMV) formation (Lundin et al.,
2014). Here we assessed potential antiviral activities of K22 against a range of
viruses representing two (sub)families of the order Nidovirales, the
Arteriviridae (porcine reproductive and respiratory syndrome virus [PRRSV],
equine arteritis virus [EAV] and simian hemorrhagic fever virus [SHFV]), and the
Torovirinae (equine torovirus [EToV] and White Bream virus [WBV]). Possible
effects of K22 on nidovirus replication were studied in suitable cell lines. K22
concentrations significantly decreasing infectious titres of the viruses included
in this study ranged from 25 to 50 MUM. Reduction of double-stranded RNA
intermediates of viral replication in nidovirus-infected cells treated with K22
confirmed the anti-viral potential of K22. Collectively, the data show that K22
has antiviral activity against diverse lineages of nidoviruses, suggesting that
the inhibitor targets a critical and conserved step during nidovirus replication.
PMID- 29337163
TI - Utility of ultra-deep sequencing for detection of varicella-zoster virus
antiviral resistance mutations.
AB - We report the first application of ultra-deep sequencing (UDS) to varicella
zoster virus (VZV) genotypic antiviral testing in a case of acyclovir-resistant
VZV infection initially detected by Sanger sequencing within a deeply
immunocompromised heart transplant recipient. As added-value compared to Sanger
analysis, UDS revealed complex dynamics of viral population under antiviral
pressure. Varicella-zoster virus (VZV) is a ubiquitous human herpesvirus
affecting populations worldwide. VZV is commonly acquired in youth whose primary
infection usually manifests as benign varicella (chickenpox). After the initial
infection, the virus establishes lifelong latency in sensory ganglia leading to a
risk of subsequent reactivation. Reactivation usually results in the development
of localized herpes zoster (HZ) lesions, a painful skin rash commonly known as
shingles (Cohen, 2013). The incidence and severity of HZ increase with impaired
specific cell-mediated immunity mainly as a result of increasing age, malignancy,
immunodeficiency, organ transplantation, or immunosuppressive drug therapy
(Cohen, 2013; Koo et al., 2014; Pavlopoulou et al., 2015). In particular, HZ
remains a significant cause of morbidity among solid organ transplant (SOT)
recipients, especially in patients undergoing heart transplantation (HT) compared
with liver, kidney, or lung transplant recipients (Carby et al., 2007; Koo et
al., 2014; Pavlopoulou et al., 2015). These particular individuals are at
increased risk of primary infection, reactivation followed by dissemination with
visceral involvement and associated with bacterial superinfection, and chronic
recurrences (Cohen, 2013). VZV infections may also engender debilitating
neuralgia among highly immunocompromised patients (Sampathkumar et al., 2009). HT
is also associated with the risk of reactivation of other latent viruses
belonging to the Herpesviridae family as herpes simplex virus (HSV). Currently
licensed drugs to prevent or to cure HSV- or VZV-associated diseases target the
viral DNA polymerase (Pol). Acyclovir (ACV) and its prodrug valacyclovir (VACV)
are considered as the first-line therapy, whereas foscarnet (FOS) or cidofovir
(CDV) constitute alternative options. After primophosphorylation by the viral
thymidine kinase (TK), ACV targets the viral DNA polymerase and inhibits the
viral genome replication by a chain termination mechanism. According to this
mechanism of action, viral mutations conferring resistance to ACV have been
mapped both in TK and Pol encoding genes. Viral mutations conferring resistance
to FOS and CDV are only detected in Pol gene. VZV ACV-resistance is mostly
mediated by TK alterations, consisting in either translational frameshifts,
sometimes associated with premature stop codon, or amino acid substitutions. In
the remaining cases, amino acid substitutions are detected within Pol (De et al.,
2015; Piret and Boivin, 2014). Classically, Sanger sequencing has been recognized
as the gold standard for the detection of drug resistance mutations (DRMs) within
VZV TK and Pol genes (Perrier et al., 2016; Piret and Boivin, 2014). However,
this approach cannot detect minor variants present at a frequency below 20%.
Ultra-deep sequencing (UDS) has an enhanced sensitivity compared to Sanger method
and allows quantitative evaluation of the viral mutants (Chin et al., 2013). We
report here a case of VZV resistant infection in an HT recipient. Our
retrospective study aimed at showing the utility of UDS for DRM detection as a
complement of Sanger method.
PMID- 29337164
TI - Identification of novel antivirals inhibiting recognition of Venezuelan equine
encephalitis virus capsid protein by the Importin alpha/beta1 heterodimer through
high-throughput screening.
AB - Although the alphavirus Venezuelan equine encephalitis virus (VEEV) has been the
cause of multiple outbreaks resulting in extensive human and equine mortality and
morbidity, there are currently no anti-VEEV therapeutics available. VEEV
pathogenicity is largely dependent on targeting of the viral capsid protein (CP)
to the host cell nucleus through the nuclear transporting importin (Imp)
alpha/beta1 heterodimer. Here we perform a high-throughput screen, combined with
nested counterscreens to identify small molecules able to inhibit the
Impalpha/beta1:CP interaction for the first time. Several compounds were able to
significantly reduce viral replication in infected cells. Compound G281-1564 in
particular could inhibit VEEV replication at low MUM concentration, while showing
minimal toxicity, with steady state and dynamic quantitative microscopic
measurements confirming its ability to inhibit CP nuclear import. This study
establishes the principle that inhibitors of CP nucleocytoplasmic trafficking can
have potent antiviral activity against VEEV, and represents a platform for future
development of safe anti-VEEV compounds with high efficacy and specificity.
PMID- 29337165
TI - Establishment of intracellular tenofovir-diphosphate as the key determinant for
in vitro-in vivo translation of antiviral efficacy.
AB - In vitro evaluation of tenofovir disproxil fumarate (TDF) and tenofovir
alafenamide (TAF) revealed comparable antiviral effects with respect to the
tenofovir-diphosphate (TFV-DP) level in human peripheral blood mononuclear cells
(PBMCs), despite the EC50 values determined based on prodrug concentrations were
nearly two orders of magnitude apart. In vivo EC50 obtained from meta-analyses
were in good agreement with the in vitro results, indicating intracellular TFV-DP
can be employed for in vitro-in vivo translation of viral inhibition for
tenofovir prodrugs. Current analysis indicated that the intracellular
concentrations of TFV-DP achieving maximal antiviral effect in vitro can be
directly translatable in the clinic to accomplish maximal viral load suppression
attainable by tenofovir-prodrugs.
PMID- 29337166
TI - CD163 knockout pigs are fully resistant to highly pathogenic porcine reproductive
and respiratory syndrome virus.
AB - Porcine reproductive and respiratory syndrome virus (PRRSV) causes severe
economic losses to current swine production worldwide. Highly pathogenic PRRSV
(HP-PRRSV), originated from a genotype 2 PRRSV, is more virulent than classical
PRRSV and further exacerbates the economic impact. HP-PRRSV has become the
predominant circulating field strain in China since 2006. CD163 is a cellular
receptor for PRRSV. The depletion of CD163 whole protein or SRCR5 region
(interaction site for the virus) confers resistance to infection of several PRRSV
isolates in pigs or cultured host cells. In this study, we described the
generation of a CD163 knockout (KO) pig in which the CD163 protein was ablated by
using CRISPR/Cas9 gene targeting and somatic cell nuclear transfer (SCNT)
technologies. Challenge with HP-PRRSV TP strain showed that CD163 KO pigs are
completely resistant to viral infection manifested by the absence of viremia,
antibody response, high fever or any other PRRS-associated clinical signs. By
comparison, wild-type (WT) controls displayed typical signs of PRRSV infection
and died within 2 weeks after infection. Deletion of CD163 showed no adverse
effects to the macrophages on immunophenotyping and biological activity as
hemoglobin-haptoglobin scavenger. The results demonstrated that CD163 knockout
confers full resistance to HP-PRRSV infection to pigs without impairing the
biological function associated with the gene.
PMID- 29337167
TI - Prognostic Factors for Survival Outcome of High-Grade Multicentric Glioma.
AB - OBJECTIVE: The purpose of this study was to perform a survival analysis of
patients with high-grade multicentric gliomas and to assess the influence of
various prognostic factors on overall survival (OS). METHODS: A literature search
on PubMed and Web of Science was performed for literature in English published
from 1880 to October 2017. Detailed information including demographics, clinical
characteristics, treatments, critical events, and time to events for survival
analysis were extracted from the included articles. RESULTS: A total of 73 cases
from 25 published articles were selected for analysis. Univariate analysis showed
the surgery (SB/SR), age (<54/>=54 years), radiotherapy (Y/N), and
suprainfratentorial gliomas (Y/N) had significant correlations with OS.
Multivariate analysis showed that age, surgery, and radiotherapy were independent
prognostic factors. Univariate and multivariate analysis revealed radiotherapy
and radiotherapy combined with chemotherapy were independent prognostic factors
for surgical patients' OS. CONCLUSIONS: This comprehensive analysis of
multicentric glioma patients revealed that age younger than 54 years, surgical
resection, and radiotherapy were significantly associated with improved survival
and were independent prognostic factors for OS. Radiotherapy and radiotherapy
combined with chemotherapy were independent prognostic factors for surgical
patients' OS as well.
PMID- 29337168
TI - Aggressive Resection of Congenital Lumbosacral Lipomas in Adults: Indications,
Techniques, and Outcomes in 122 Patients.
AB - OBJECTIVE: The authors reviewed the treatment of adult patients with congenital
intraspinal lipomas with total/near-total resection and discussed their
preoperative characteristics, prognostic factors, and surgical outcomes. METHODS:
Medical records of 122 adult patients with congenital lumbosacral lipomas
undergoing total/near-total resection were systematically analyzed. The cohort
was subdivided into 3 groups depending on symptom onset age: group 1 (<=5 years,
n = 40), group 2 (>5 years but <18 years, n = 33), and group 3 (>18 years, n =
49). Preoperative and postoperative neurologic status were compared between
groups and analyzed as a whole. RESULTS: The most common symptom was bladder
dysfunction (82.0%), followed by constipation (76.2%). At the 3-month follow-up,
improvement was noted in most patients presenting with pain (87.2%) and
neuropathic ulcers (70.0%). Overall, neurologic status was improved in 73.0% of
patients and stabilized in 19.7% of patients. A binary logistic regression model
identified shorter preoperative duration (P = 0.013) and preoperative pain (P =
0.005) as independent predictors of postoperative improvement. Neurosurgical
complications developed in 16 patients, and wound complications occurred in 2
patients. Two of 3 patients who had recurred symptoms underwent repeated
detethering surgery during long-term follow-up. CONCLUSIONS: Despite longer
preoperative duration than the pediatric population, adult patients with
lumbosacral lipomas can still benefit from total/near-total resection especially
regarding pain and foot ulcers, with low surgery-related morbidity. The long-term
advantage of resecting additional lipoma in adults remains a point of discussion.
PMID- 29337170
TI - Virtual Cerebral Aneurysm Clipping with Real-Time Haptic Force Feedback in
Neurosurgical Education.
AB - OBJECTIVE: Realistic, safe, and efficient modalities for simulation-based
training are highly warranted to enhance the quality of surgical education, and
they should be incorporated in resident training. The aim of this study was to
develop a patient-specific virtual cerebral aneurysm-clipping simulator with
haptic force feedback and real-time deformation of the aneurysm and vessels.
METHODS: A prototype simulator was developed from 2012 to 2016. Evaluation of
virtual clipping by blood flow simulation was integrated in this software, and
the prototype was evaluated by 18 neurosurgeons. In 4 patients with different
medial cerebral artery aneurysms, virtual clipping was performed after real-life
surgery, and surgical results were compared regarding clip application, surgical
trajectory, and blood flow. RESULTS: After head positioning and craniotomy,
bimanual virtual aneurysm clipping with an original forceps was performed. Blood
flow simulation demonstrated residual aneurysm filling or branch stenosis. The
simulator improved anatomic understanding for 89% of neurosurgeons. Simulation of
head positioning and craniotomy was considered realistic by 89% and 94% of users,
respectively. Most participants agreed that this simulator should be integrated
into neurosurgical education (94%). Our illustrative cases demonstrated that
virtual aneurysm surgery was possible using the same trajectory as in real-life
cases. Both virtual clipping and blood flow simulation were realistic in broad
based but not calcified aneurysms. Virtual clipping of a calcified aneurysm could
be performed using the same surgical trajectory, but not the same clip type.
CONCLUSIONS: We have successfully developed a virtual aneurysm-clipping
simulator. Next, we will prospectively evaluate this device for surgical
procedure planning and education.
PMID- 29337171
TI - Is Early Tracheostomy Better for Severe Traumatic Brain Injury? A Meta-Analysis.
AB - BACKGROUND: Tracheostomy has proven benefits for patients requiring prolonged
mechanical ventilation. However, whether early tracheostomy (ET; <10 days after
injury) can also improve outcomes in patients with severe traumatic brain injury
(TBI) (Glasgow Coma Scale score <=8) remains controversial. The aim of this study
was to clarify this question. METHODS: We searched 4 databases (PubMed, Web of
Science, Elsevier ScienceDirect, and Cochrane Library) for articles comparing the
outcomes of ET with late tracheotomy or prolonged intubation in patients with
severe TBI. Two reviewers were asked to record the major outcome data as follows:
length of intensive care unit (ICU) stay, duration of mechanical ventilation,
mortality, and incidence of pneumonia. Both random-effects and fixed-effects
models were used. RESULTS: Eight studies met our inclusion criteria, with a total
of 797 patients in the ET group and 871 patients in the late tracheostomy or
prolonged intubation (not-ET) group. A meta-analysis of these 8 studies suggested
that ET could reduce the length of ICU stay (mean difference [MD], -3.08; 95%
confidence interval [CI], -3.75 to -2.41), duration of mechanical ventilation
(MD, -4.92; 95% CI, -6.82 to -3.02), length of hospital stay (MD, -4.79; 95% CI,
8.63 to -0.94), and incidence of pneumonia (odds ratio [OR], 0.64; 95% CI, 0.53
0.78), but seemed to be independent of mortality (OR, 1.25; 95% CI, 0.90-1.75).
CONCLUSIONS: The available evidence suggests that ET may reduce the length of ICU
and hospital stays, duration of mechanical ventilation, and incidence of
pneumonia in patients with severe TBI. Well-designed randomized controlled trials
are needed to confirm these findings.
PMID- 29337169
TI - The Prognostic Roles of Gender and O6-Methylguanine-DNA Methyltransferase
Methylation Status in Glioblastoma Patients: The Female Power.
AB - BACKGROUND: Clinical and molecular factors are essential to define the prognosis
in patients with glioblastoma (GBM). O6-methylguanine-DNA methyltransferase
(MGMT) methylation status, age, Karnofsky Performance Status (KPS), and extent of
surgical resection are the most relevant prognostic factors. Our investigation of
the role of gender in predicting prognosis shows a slight survival advantage for
female patients. METHODS: We performed a prospective evaluation of the Project of
Emilia Romagna on Neuro-Oncology (PERNO) registry to identify prognostic factors
in patients with GBM who received standard treatment. RESULTS: A total of 169
patients (99 males [58.6%] and 70 females [41.4%]) were evaluated prospectively.
MGMT methylation was evaluable in 140 patients. Among the male patients, 36 were
MGMT methylated (25.7%) and 47 were unmethylated (33.6%); among the female
patients, 32 were methylated (22.9%) and 25 were unmethylated (17.9%). Survival
was longer in the methylated females compared with the methylated males (P =
0.028) but was not significantly different between the unmethylated females and
the unmethylated males (P = 0.395). In multivariate analysis, gender and MGMT
methylation status considered together (methylated females vs. methylated males;
hazard ratio [HR], 0.459; 95% confidence interval [CI], 0.242-0.827; P = 0.017),
age (HR, 1.025; 95% CI, 1.002-1.049; P = 0.032), and KPS (HR, 0.965; 95% CI,
0.948-0.982; P < 0.001) were significantly correlated with survival. CONCLUSIONS:
Survival was consistently longer among MGMT methylated females compared with
males. Gender can be considered as a further prognostic factor.
PMID- 29337173
TI - Improving bystander defibrillation for out-of-hospital cardiac arrest:
Capability, opportunity and motivation.
PMID- 29337172
TI - Organ support therapy in the intensive care unit and return to work in out-of
hospital cardiac arrest survivors-A nationwide cohort study.
AB - AIM: With increased survival after out-of-hospital cardiac arrest (OHCA), impact
of the post-resuscitation course has become important. Among 30-day OHCA
survivors, we investigated associations between organ support therapy in the
Intensive Care Unit (ICU) and return to work. METHODS: This Danish nationwide
cohort-study included 30-day-OHCA-survivors who were employed prior to arrest. We
linked OHCA data to information on in-hospital care and return to work. For
patients admitted to an ICU and based on renal replacement therapy (RRT),
cardiovascular support and mechanical ventilation, we assessed the prognostic
value of organ support therapies in multivariable Cox regression models. RESULTS:
Of 1087 30-day survivors, 212 (19.5%) were treated in an ICU with 0-1 types of
organ support, 494 (45.4%) with support of two organs, 26 (2.4%) with support of
three organs and 355 (32.7%) were not admitted to an ICU. Return to work
increased with decreasing number of organs supported, from 53.8% (95% CI: 49.5
70.1%) in patients treated with both RRT, cardiovascular support and mechanical
ventilation to 88.5% (95% CI: 85.1-91.8%) in non-ICU-patients. In 732 ICU
patients, ICU-patients with support of 3 organs had significantly lower adjusted
hazard ratios (HR) of returning to work (0.50 [95% CI: 0.30-0.85] compared to ICU
patients with support of 0-1 organ. The corresponding HR was 0.48 [95% CI: 0.30
0.78] for RRT alone. CONCLUSIONS: In 30-day survivors of OHCA, number of organ
support therapies and in particular need of RRT were associated with reduced rate
of return to work, although more than half of these latter patients still
returned to work.
PMID- 29337174
TI - Palliative care utilization following out-of-hospital cardiac arrest in the
United States.
AB - AIMS: Palliative care (PC) has become an integral component of comprehensive care
provided to critically ill patients. Little is known about the utilization of
palliative care following Out-of-Hospital Cardiac Arrest (OHCA) in the United
States. METHODS: We used the 2002-2013 National Inpatient Sample database to
identify adults >=18 years old with an ICD-9-CM principal diagnosis code of
cardio-respiratory arrest or ventricular fibrillation (VF). Patients were
categorized into two groups based on the presence of PC, then compared using
Pearson chi2 test for categorical variables and linear regression for continuous
variables. Multiple linear and logistic regression models were conducted to
identify factors associated with PC, and temporal trends in PC utilization.
RESULTS: Of the 154,177 patients hospitalized with OHCA in the U.S, 11,260 (7.3%)
had PC consultations during hospitalization. PC Utilization increased from 1.5%
in 2002 to 16.7% in 2013 (P-trend < 0.001). Patients who received Palliative care
were older (mean age 70.7 +/- 0.3 vs 65.9 +/- 0.1), more likely to be female
(45.8% vs 40.5%), and had higher Charlson comorbidity index >=2 (55.8% vs 46.8%).
In adjusted analyses, older age, female gender, Caucasian race, higher Charlson
comorbidity index, multiorgan failure, metastatic cancer, non-shockable rhythm,
admission to larger, urban and teaching hospitals were all associated with higher
PC utilization. CONCLUSION: We observed significant increase in the utilization
of palliative care consultations following OHCA over the study period. This was
influenced by multiple patient and hospital factors. Further investigations are
needed to identify the appropriate cost-effective use of palliative care
following cardiac arrest.
PMID- 29337175
TI - Minimally invasive versus extensile lateral approach for sanders type II and III
calcaneal fractures: A meta-analysis of randomized controlled trials.
AB - BACKGROUND: The use of less-invasive techniques in the treatment of displaced
intra-articular calcaneal fractures (DIACFs) remains controversial. No prior meta
analysis has considered the influence of differences in the fracture type. Thus,
our meta-analysis aimed to investigate the efficacy and safety of minimally
invasive (MI) in Sanders type II and III fractures. MATERIALS AND METHODS: A
comprehensive search was performed to identify RCTs comparing MI using sinus
tarsi approach (STA) or percutaneous reduction (PR) to open reduction (OR) via
extensile lateral approach (ELA) from the Cochrane Library, PubMed, Embase and
CNKI. Dichotomous and continuous data were pooled using risk ratio (RR) and mean
difference (MD), respectively, with 95% confidence intervals (CIs). The data were
analysed using Review Manager 5.3. RESULTS: Eight RCTs (495 participants) were
selected in our meta-analysis. Based on the American Orthopaedic Foot and Ankle
Society score (AOFAS), both general pooled data and subgroup analysis of Sanders
type II fractures indicated that MI improves functional outcomes, while in the
Sanders type III subgroup, the advantage disappeared. Additionally, the pooled
results showed that MI reduces the rate of wound complications; lowers the VAS
score; and shortens the time to surgery, duration of surgery and length of
hospital stay. There was no statistical significance with respect to recovery of
calcaneus length and width or improvement of Gissane's angle and Bohler's angle.
CONCLUSION: Our meta-analysis suggests that MI and ELA are equally effective
treating Sanders type II and III fractures. However, MI is effective in improving
the AOFAS score (Sanders type II); reducing the rate of wound complications; and
shortening the time to surgery, duration of surgery and length of hospital stay.
PMID- 29337176
TI - Comparison of the diagnostic performances of ultrasonography, CT and fine needle
aspiration cytology for the prediction of lymph node metastasis in patients with
lymph node dissection of papillary thyroid carcinoma: A retrospective cohort
study.
AB - PURPOSE: To evaluate the diagnostic performances of ultrasonographic (US)
findings, computed tomography (CT) findings and fine needle aspiration cytology
(FNAC) for the prediction of cervical lymph node (LN) metastases of papillary
thyroid carcinoma (PTC) to determine which LN should be dissected. METHODS: 376
LNs in 302 patients who underwent both US-guided skin surface LN markings and CT
before LN dissection were analyzed retrospectively. Indications for LN dissection
were suspicious US findings of LN metastases (n = 300), suspicious CT findings (n
= 67) or surgeon's request (n = 9). Diagnostic performances of US, CT and FNAC
(including thyroglobulin (Tg)) were evaluated. The correlations of suspicious US,
CT finding or malignant FNAC with the size, number and the presence of extranodal
extension of metastatic LNs were analyzed. RESULTS: US indication of LN
dissection was significantly correlated with malignancy (p < .0001). Values of
area under the curve of highly suspicious US findings and FNAC+Tg were
significantly higher than that of CT (0.786, 0.878, 0.585, p < .0001,
respectively). Suspicious US, CT findings and malignant FNAC+Tg were
significantly associated with the largest size of metastatic LNs (p = .003, p =
.0003, and p = .0006, respectively) and total number of metastatic LNs (p = .007,
p = .038, and p = .005, respectively). CONCLUSION: The diagnostic performance of
US or FNAC was superior to CT and highly suspicious US findings could be
complimentary to FNAC results in predicting LN metastases of PTC. LN dissection
should be performed for the LNs with any suspicious US findings or malignant FNAC
results rather than LNs with only suspicious CT findings.
PMID- 29337177
TI - Laparoscopic versus open pancreatectomy for pancreatic ductal adenocarcinoma: A
systematic review and meta-analysis.
AB - BACKGROUND: Laparoscopic pancreatic surgery (LPS) has been widely used in the
treatment of benign and low-grade pancreatic diseases. It is necessary to expand
the current knowledge on the feasibility and safety of LPS for pancreatic ductal
adenocarcinoma (PDAC) by systematic reviewing the published studies and analyzing
them by meta-analysis. METHODS: Original articles compared LPS with open
pancreatic surgery (OPS) for PDAC, published from January 1994 to August 2017
were searched in medical databases. Postoperative pancreatic fistula (POPF),
morbidity, mortality, operation time, blood loss, transfusion, hospital stay,
retrieved lymph nodes (RLNs), and survival outcomes were compared. RESULTS:
Fourteen studies with a total of 13174 patients (1705 in LPS and 11469 in OPS)
were included for the meta-analysis. LPS showed less morbidity (RR = 0.78, 95%CI:
0.66-0.92, P < .01), blood loss (WMD = -298.05 ml, 95% CI, -482.98~-113.12 ml; P
< .01), shorter hospital stay (WMD = -2.86, 95%CI, -3.85~-1.87; P < .01), more
RLNs (WMD = 1.47, 95%CI: 0.15-2.78; P = .03) and comparable POPF (RR = 1.12,
95%CI: 0.82-1.53, P = .50), operation time (WMD = 22.23 min; 95%CI: -19.56-64.01,
P = .30), and 5-year overall survival (HR = 0.92, 95%CI: 0.80-1.06; P = .23)
compared to OPS. CONCLUSION: LPS can be performed safely in carefully selected
patients with PADC and would improve the surgical outcomes. Considering the
limitation of study design, the conclusions should be interpret cautiously and
warrant to be confirmed by randomized controlled studies.
PMID- 29337178
TI - Multifocality as a prognostic factor in thyroid cancer: A meta-analysis.
AB - BACKGROUND: Thyroid cancer is one of the most common endocrine cancers whose
incidence has been steadily increasing. Previous studies have suggested that
multifocality in thyroid cancer is associated with poor prognosis. The present
study aims to quantify the data on multifocality as a factor indicating poor
prognosis by meta-analysis. METHODS: A systematic search was carried out using
the electronic databases PubMed and Medline. We searched for articles containing
keywords of multifocality and thyroid cancer, as well as risk factors and
prognostic factors for thyroid cancer (Lymph node metastases, extrathyroidal
extension, distant metastases, disease recurrence, Age, tumour size. and gender).
Data sets containing hazard ratios and odds ratios were then compared. RESULTS:
The meta-analysis was performed using a total of 21 articles, showed that
multifocality is associated with an increased risk of development of LNM (12
Studies: OR = 1.87; 95% CI = 1.51-2.32; I2 = 49.11; p-value = .03),
Extrathyroidal extension (15 Studies: OR = 3.18; 95% CI = 0.69-14.71; I2 = 95.62;
p-value <.001), Tumour Size > 1 cm (3 Studies: OR = 2.75; 95% CI = 1.95-3.89; I2
= 0.00 and p-value = .88) and disease recurrence (5 Studies: HR = 2.81; 95% CI =
1.07-7.36; I2 = 95.85; p-value < .001). Risk factors that did not significantly
contribute to a higher incidence of multifocality include Age >45, Male Gender.
CONCLUSIONS: Multifocality in thyroid cancer is a significant risk factor for
disease progression and increases the risk of disease recurrence. The present
study suggests that patients who have multifocal disease should therefore be
managed more aggressively from an operative and post-operative perspective.
PMID- 29337179
TI - Surgical treatment of recurrent varicose veins in the lower limbs associated with
endovascular treatment of iliac vein stenosis.
AB - OBJECTIVE: We present our experience with endovascular surgery for recurrent
varicose veins (RVV) of the lower limbs combined with the iliac vein compression
syndrome (IVCS). MATERIALS AND METHODS: This study was a retrospective analysis
of 6 patients with RVVs combined with IVCS who were admitted to our hospital
between January 2007 and December 2014. Transfemoral venography was performed to
confirm IVCS. Balloon dilation and stent placement were successful in all 6
patients. The varicose veins were treated by traditional surgery after the
endovascular therapy. The visual analog pain scale (VAS) score and venous
clinical severity score (VCSS) were collected before surgery and at 6-months
follow-up, and were analyzed using the paired student t-test. Patency of the
iliac vein was assessed via duplex Doppler ultrasound. RESULTS: The rate of
technical success was 100%. There was a significant (p < .001) improvement in
VCSS postoperatively. During the 6-month follow-up period, no RVVs were observed
and the rate of iliac vein patency was 100%. Importantly, VAS ratings also
decreased significantly (p < .001) during the follow-up. CONCLUSION: Endovascular
surgery for IVCS combined with traditional surgery focused on varicose veins is
an effective procedure for treating RVVs of the lower limbs associated with IVCS
within 6 months.
PMID- 29337180
TI - Impact of an acute surgical unit in appendicectomy outcomes: A systematic review
and meta-analysis.
AB - BACKGROUND: The provision of emergency general surgical services is undergoing a
paradigm shift towards a consultant led, patient centered model in order to
improve patient outcomes. The aim of this current study is to use meta-analytical
techniques to assess the efficacy of acute surgical unit (ASU) in appendectomy.
METHODS: A meta-analysis was conducted according to the PRISMA guidelines. A
comprehensive literature search of PubMed, Embase and Scopus for published
studies comparing ASU and traditional (TRAD) model on appendectomy outcomes was
performed. Random-effects methods were used to analyze key outcomes with data
presented as odds ratio (OR) with 95% confidence interval (CI). RESULTS: Fourteen
comparative studies describing outcomes in 7980 patients were identified, 4258
patients were included in the ASU model (53.4%). ASU model had a shorter time to
theatre (WMD: -0.40, 95% CI: -0.65 to 0.15, p: 0.002), length of hospital stay
(WMD: -0.25, 95% CI: -0.46 to -0.05, p: 0.02) and complication rate (OR: 0.76,
95% CI: 0.59 to 0.99, p: 0.04) for appendectomy patients. ASU model did not
significantly affect night time operating (OR: 1.04, 95% CI: 0.66 to 1.65, p:
0.86) negative appendectomy rates (OR: 0.98, 95% CI: 0.77-1.27, p: 0.91) or
conversion rate (OR: 1.45, 95% CI: 0.70 to 2.98, p: 0.32). CONCLUSION: ASU model
improves outcomes and quality of care in patients undergoing emergency
appendectomy without any adverse implications.
PMID- 29337182
TI - Human Pancreatic Tumor Organoids Reveal Loss of Stem Cell Niche Factor Dependence
during Disease Progression.
AB - Despite recent efforts to dissect the inter-tumor heterogeneity of pancreatic
ductal adenocarcinoma (PDAC) by determining prognosis-predictive gene expression
signatures for specific subtypes, their functional differences remain elusive.
Here, we established a pancreatic tumor organoid library encompassing 39 patient
derived PDACs and identified 3 functional subtypes based on their stem cell niche
factor dependencies on Wnt and R-spondin. A Wnt-non-producing subtype required
Wnt from cancer-associated fibroblasts, whereas a Wnt-producing subtype
autonomously secreted Wnt ligands and an R-spondin-independent subtype grew in
the absence of Wnt and R-spondin. Transcriptome analysis of PDAC organoids
revealed gene-expression signatures that associated Wnt niche subtypes with GATA6
dependent gene expression subtypes, which were functionally supported by genetic
perturbation of GATA6. Furthermore, CRISPR-Cas9-based genome editing of PDAC
driver genes (KRAS, CDKN2A, SMAD4, and TP53) demonstrated non-genetic acquisition
of Wnt niche independence during pancreas tumorigenesis. Collectively, our
results reveal functional heterogeneity of Wnt niche independency in PDAC that is
non-genetically formed through tumor progression.
PMID- 29337181
TI - A Non-canonical BCOR-PRC1.1 Complex Represses Differentiation Programs in Human
ESCs.
AB - Polycomb group proteins regulate self-renewal and differentiation in many stem
cell systems. When assembled into two canonical complexes, PRC1 and PRC2, they
sequentially deposit H3K27me3 and H2AK119ub histone marks and establish
repressive chromatin, referred to as Polycomb domains. Non-canonical PRC1
complexes retain RING1/RNF2 E3-ubiquitin ligases but have unique sets of
accessory subunits. How these non-canonical complexes recognize and regulate
their gene targets remains poorly understood. Here, we show that the BCL6 co
repressor (BCOR), a member of the PRC1.1 complex, is critical for maintaining
primed pluripotency in human embryonic stem cells (ESCs). BCOR depletion leads to
the erosion of Polycomb domains at key developmental loci and the initiation of
differentiation along endoderm and mesoderm lineages. The C terminus of BCOR
regulates the assembly and targeting of the PRC1.1 complex, while the N terminus
contributes to BCOR-PRC1.1 repressor function. Our findings advance understanding
of Polycomb targeting and repression in ESCs and could apply broadly across
developmental systems.
PMID- 29337183
TI - Temporal Layering of Signaling Effectors Drives Chromatin Remodeling during Hair
Follicle Stem Cell Lineage Progression.
AB - Tissue regeneration relies on resident stem cells (SCs), whose activity and
lineage choices are influenced by the microenvironment. Exploiting the
synchronized, cyclical bouts of tissue regeneration in hair follicles (HFs), we
investigate how microenvironment dynamics shape the emergence of stem cell
lineages. Employing epigenetic and ChIP-seq profiling, we uncover how signal
dependent transcription factors couple spatiotemporal cues to chromatin dynamics,
thereby choreographing stem cell lineages. Using enhancer-driven reporters,
mutagenesis, and genetics, we show that simultaneous BMP-inhibitory and WNT
signals set the stage for lineage choices by establishing chromatin platforms
permissive for diversification. Mechanistically, when binding of BMP effector
pSMAD1 is relieved, enhancers driving HF-stem cell master regulators are
silenced. Concomitantly, multipotent, lineage-fated enhancers silent in HF-stem
cells become activated by exchanging WNT effectors TCF3/4 for LEF1. Throughout
regeneration, lineage enhancers continue reliance upon LEF1 but then achieve
specificity by accommodating additional incoming signaling effectors. Barriers to
progenitor plasticity increase when diverse, signal-sensitive transcription
factors shape LEF1-regulated enhancer dynamics.
PMID- 29337184
TI - When drugs plasticize film coatings: Unusual formulation effects observed with
metoprolol and Eudragit RS.
AB - Metoprolol tartrate and metoprolol free base loaded pellet starter cores were
coated with Eudragit RS, plasticized with 25% triethyl citrate (TEC). The initial
drug loading and coating level were varied from 10 to 40 and 0 to 20%,
respectively. Drug release was measured in 0.1 N HCl and phosphate buffer pH 7.4.
The water uptake and swelling kinetics, mechanical properties and TEC leaching
of/from coated pellets and/or thin, free films of identical composition as the
film coatings were monitored. The following unusual tendencies were observed: (i)
the relative drug release rate from coated pellets increased with increasing
initial drug content, and (ii) drug release from pellets was much faster for
metoprolol free base compared to metoprolol tartrate, despite its much lower
solubility (factor >70). These phenomena could be explained by plasticizing
effects of the drug for the polymeric film coatings. In particular: 1) Metoprolol
free base is a much more potent plasticizer for Eudragit RS than the tartrate,
leading to higher film permeability and overcompensating the pronounced
differences in drug solubility. Also, Raman imaging revealed that substantial
amounts of the free base migrated into the film coatings, whereas this was not
the case for the tartrate. 2) The plasticizing effects of the drug for the film
coating overcompensated potential increasing limited solubility effects when
increasing the initial drug loading from 10 to 40%. In summary, this study
clearly demonstrates how important the plasticization of polymeric controlled
release film coatings by drugs can be, leading to unexpected formulation effects.
PMID- 29337185
TI - Proliposome tablets manufactured using a slurry-driven lipid-enriched powders:
Development, characterization and stability evaluation.
AB - Proliposome powders were prepared via a slurry method using sorbitol or D
mannitol as carbohydrate carriers in 1:10 or 1:15 w/w lipid phase to carrier
ratios. Soya phosphatidylcholine (SPC) and cholesterol were employed as a lipid
phase and Beclometasone dipropionate (BDP) was incorporated as a model drug.
Direct compaction using a Minipress was applied on the lipid-enriched powder in
order to manufacture proliposome tablets. Sorbitol-based proliposome tablets in a
1:15 w/w ratio were found to be the best formulation as it exhibited excellent
powder flowability with an angle of repose of 25.62 +/- 1.08 degrees , and when
compacted the resultant tablets had low friability (0.20 +/- 0.03%), appropriate
hardness (crushing strength) (120.67 +/- 12.04 N), short disintegration time
(5.85 +/- 0.66 min), and appropriate weight uniformity. Moreover, upon hydration
into liposomes, the entrapment efficiency for sorbitol formulations in both 1:10
and 1:15 lipid to carrier ratios were significantly higher (53.82 +/- 6.42% and
57.43 +/- 9.12%) than D-mannitol formulations (39.90 +/- 4.30% and 35.22 +/-
6.50%), respectively. Extended stability testing was conducted for 18 months, at
three different temperature conditions (Fridge Temperature (FT; 6 degrees C),
Room Temperature (RT; 22 degrees C) and High Temperature (HT; 40 degrees C))
for sorbitol-based proliposome tablets (1:15 w/w ratio). Volume median diameter
(VMD) and zeta potential significantly changed from 5.90 +/- 0.70 um to 14.79 +/-
0.79 um and from -3.08 +/- 0.26 mV to -11.97 +/- 0.26 mV respectively at month
18, when samples were stored under HT conditions. Moreover, the entrapment
efficiency of BDP decreased from 57.43 +/- 9.12% to 17.93 +/- 5.37% following 18
months storage under HT conditions. Overall, in this study for the first time,
proliposome tablets were manufactured and thoroughly characterized, and sorbitol
showed to be a promising carrier.
PMID- 29337186
TI - Lipoprotein Signal Peptidase Inhibitors with Antibiotic Properties Identified
through Design of a Robust In Vitro HT Platform.
AB - As resistance to antibiotics increases, the exploration of new targets and
strategies to combat pathogenic bacteria becomes more urgent. Ideal protein
targets are required for viability across many species, are unique to prokaryotes
to limit effects on the host, and have robust assays to quantitate activity and
identify inhibitors. Lipoprotein signal peptidase (Lsp) is a transmembrane
aspartyl protease required for lipoprotein maturation and comprehensively fits
these criteria. Here, we have developed the first in vitro high-throughput assay
to monitor proteolysis by Lsp. We employed our high-throughput screen assay
against 646,275 compounds to discover inhibitors of Lsp and synthesized a range
of analogs to generate molecules with nanomolar half maximal inhibitory
concentration values. Importantly, our inhibitors are effective in preventing the
growth of E. coli cultures in the presence of outer-membrane permeabilizer PMBN
and should facilitate development of antibacterial agents with a novel mechanism
of action to treat antibiotic-resistant bacteria.
PMID- 29337187
TI - Metabolomics Reveals that Dietary Xenoestrogens Alter Cellular Metabolism Induced
by Palbociclib/Letrozole Combination Cancer Therapy.
AB - Recently, the palbociclib/letrozole combination therapy was granted accelerated
US FDA approval for the treatment of estrogen receptor (ER)-positive breast
cancer. Since the underlying metabolic effects of these drugs are yet unknown, we
investigated their synergism at the metabolome level in MCF-7 cells. As
xenoestrogens interact with the ER, we additionally aimed at deciphering the
impact of the phytoestrogen genistein and the estrogenic mycotoxin zearalenone. A
global metabolomics approach was applied to unravel metabolite and pathway
modifications. The results clearly showed that the combined effects of
palbociclib and letrozole on cellular metabolism were far more pronounced than
that of each agent alone and potently influenced by xenoestrogens. This behavior
was confirmed in proliferation experiments and functional assays. Specifically,
amino acids and central carbon metabolites were attenuated, while higher
abundances were observed for fatty acids and most nucleic acid-related
metabolites. Interestingly, exposure to model xenoestrogens appeared to
counteract these effects.
PMID- 29337189
TI - A well-circumscribed lobulated tumor on the hard palatal mucosa in a child.
PMID- 29337188
TI - Abrogation of Fam20c altered cell behaviors and BMP signaling of immortalized
dental mesenchymal cells.
AB - FAM20C mutations compromise the mineralization of skeleton and tooth in both
human and mouse. Putatively, the mineralization disorder is attributed to the
elevated fibroblast growth factor 23 (FGF23), which reduced the serum phosphorus
by suppressing the reabsorption of phosphorus in kidney. Besides the regulation
on systemic phosphorus homeostasis, FAM20C was also implicated to regulate cell
behaviors and gene expression through a cell-autonomous manner. To identify the
primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient
dental mesenchymal cells were generated by removing the floxed alleles from the
immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing
lentivirus. The removal of Fam20c exerted no impact on cell morphology, but
suppressed the proliferation and mobility of the dental mesenchymal cells. Fam20c
deficiency also significantly reduced the expression of Osterix, Runx2, type I
Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small
integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased
Fgf23 expression. Consistently, the in vitro mineralization of Fam20c-deficient
dental mesenchymal cells was severely disabled. However, supplements of the non
collagenous proteins from wild type rat dentin failed to rescue the compromised
mineralization, suggesting that the roles of FAM20C in tooth mineralization are
more than phosphorylating local matrices and regulating systemic phosphorus
metabolism. Moreover, the down-regulated BMP signaling pathways in the Fam20c
deficient dental mesenchymal cells revealed that the kinase activity of FAM20C
might be required to maintain BMP signaling. In summary, our study discloses that
Fam20c indeed regulates cell behaviors and cell signaling pathway in a cell
autonomous manner.
PMID- 29337191
TI - The classification of azodicarbonamide (ADCA) as a respiratory sensitiser; adding
to the weight of evidence.
PMID- 29337190
TI - Binding of ferredoxin to algal photosystem I involves a single binding site and
is composed of two thermodynamically distinct events.
AB - Despite the impressive progress made in recent years in understanding the early
steps in charge separation within the photosynthetic reaction centers, our
knowledge of how ferredoxin (Fd) interacts with the acceptor side of photosystem
I (PSI) is not as well developed. Fd accepts electrons after transiently docking
to a binding site on the acceptor side of PSI. However, the exact location, as
well as the stoichiometry, of this binding have been a matter of debate for more
than two decades. Here, using Isothermal Titration Calorimetry (ITC) and purified
components from wild type and mutant strains of the green algae Chlamydomonas
reinhardtii we show that PSI has a single binding site for Fd, and that the
association consists of two distinct binding events, each with a specific
association constant.
PMID- 29337192
TI - Combining machine learning models of in vitro and in vivo bioassays improves rat
carcinogenicity prediction.
AB - In vitro genotoxicity bioassays are cost-efficient methods of assessing potential
carcinogens. However, many genotoxicity bioassays are inappropriate for detecting
chemicals eliciting non-genotoxic mechanisms, such as tumour promotion, this
necessitates the use of in vivo rodent carcinogenicity (IVRC) assays. In silico
IVRC modelling could potentially address the low throughput and high cost of this
assay. We aimed to develop and combine computational QSAR models of novel
bioassays for the prediction of IVRC results and compare with existing software.
QSAR models were generated from existing Ames (n = 6512), Syrian Hamster
Embryonic (SHE, n = 410), ISSCAN rodent carcinogenicity (ISC, n = 834) and
GreenScreen GADD45a-GFP (n = 1415) chemical datasets. These models mapped the
molecular descriptors of each compound to their respective assay result using
machine learning algorithms (adaboost, k-Nearest Neighbours, C.45 Decision Tree,
Multilayer Perceptron, Random Forest). The best performing models were combined
with k-Nearest Neighbours to create a cascade model for IVRC prediction. High
QSAR model performance was observed from ten time 10-fold cross-validation with
above 80% accuracy and 0.85 AUC for each assay dataset. The cascade model
predicted rat carcinogenicity with 69.3% accuracy and 0.700 AUC. This study
demonstrates the novelty of a combined approach for IVRC prediction, with higher
performance than existing software.
PMID- 29337193
TI - IL-1beta augments H2S-induced increase in intracellular Ca2+ through polysulfides
generated from H2S/NO interaction.
AB - H2S has excitatory and inhibitory effects on Ca2+ signals via transient receptor
potential ankyrin 1 (TRPA1) and ATP-sensitive K+ channels, respectively. H2S
converts intracellularly to polysulfides, which are more potent agonists for
TRPA1 than H2S. Under inflammatory conditions, changes in the expression and
activity of these H2S target channels and/or the conversion of H2S to
polysulfides may modulate H2S effects. Effects of proinflammatory cytokines on
H2S-induced Ca2+ signals and polysulfide production in RIN14B cells were examined
using fluorescence imaging with fura-2 and SSP4, respectively. Na2S, a H2S donor,
induced 1) the inhibition of spontaneous Ca2+ signals, 2) inhibition followed by
[Ca2+]i increase, and 3) rapid [Ca2+]i increase without inhibition in 50%
(23/46), 22% (10/46), and 17% (8/46) of cells tested, respectively. IL-1beta
augmented H2S-induced [Ca2+]i increases, which were inhibited by TRPA1 and
voltage-dependent L-type Ca2+ channel blockers. However, IL-1beta treatment did
not affect [Ca2+]i increases evoked by a TRPA1 agonist or high concentration of
KCl. Na2S increased intracellular polysulfide levels, which were enhanced by IL
1beta treatment. A NOS inhibitor suppressed the increased polysulfide production
and [Ca2+]i increase in IL-1beta-treated cells. These results suggest that IL
1beta augments H2S-induced [Ca2+]i increases via the conversion of H2S to
polysulfides through NO synthesis, but not via changes in the activity and
expression of target channels. Polysulfides may play an important role in the
effects of H2S during inflammation.
PMID- 29337194
TI - Fasudil ameliorates the ischemia/reperfusion oxidative injury in rat hearts
through suppression of myosin regulatory light chain/NADPH oxidase 2 pathway.
AB - Fasudil is a potent Rho-kinase (ROCK) inhibitor and can relax smooth muscle or
cardiac muscle contraction through decreasing the phosphorylation level of myosin
regulatory light chain (p-MLC20 or p-MLC2v), while p-MLC2v can function as a
transcription factor to promote the NADPH oxidase 2 (NOX2) expression in rat
hearts subjected to ischemia/reperfusion (I/R). This study aims to explore
whether fasudil can protect the rat hearts against I/R oxidative injury through
suppressing NOX2 expression via reduction of p-MLC2v level. The SD rat hearts
were subjected to 1h-ischemia plus 3h-reperfusion, which showed myocardial
injuries (myocardial fiber loss and disarray, increase of creatine kinase release
and myocardial infarction/apoptosis), increase in ROCK activity and nuclear p
MLC2v level concomitant with up-regulation of NOX2 and H2O2 production; these
phenomena were attenuated by fasudil in a dose-dependent manner. Next, we
verified the cardioprotective effect of fasudil and the underlying mechanisms in
hypoxia-reoxygenation (H/R) -treated H9c2 cells. Consistent with the results in
vivo, the H/R-treated H9c2 cells showed cellular injury (increase in apoptotic
ratio), elevation in ROCK activity and nuclear p-MLC2v level, accompanied by up
regulation of NOX2 and H2O2 production; these effects were blocked in the
presence of fasudil in a dose-dependent way. Based on these observations, we
conclude that beneficial effect of fasudil against myocardial I/R or H/R
oxidative injury is related to the suppression of NOX2 expression through
decrease of the p-MLC2v level. Our findings also highlight that intervention of
MLC2v phosphorylation by drugs may provide a novel strategy to protect heart from
I/R oxidative injury.
PMID- 29337195
TI - Secretoneurin suppresses cardiac hypertrophy through suppression of oxidant
stress.
AB - The neuropeptide secretoneurin (SN) plays protective roles in myocardial
ischemia. In the present study, the effect of SN in cardiac hypertrophy was
investigated. We observed that, in isoproterenol (ISO) treatment induced cardiac
or cardiomyocytes hypertrophy, a marked increase in the expression of endogenous
SN in mouse plasma, myocardium and primary-cultured cardiomyocytes occurs. In
hypertrophic mice, the heart size, heart weight/body weight (HW/BW) ratio,
cardiomyocyte size, and atrial natriuretic peptide (ANP) and brain natriuretic
peptide (BNP) expression were significantly higher than those in controls but
were effectively suppressed by SN gene therapy. Similarly, the protective effects
of SN were also observed in cultured cardiomyocytes following ISO treatment. SN
significantly increased the activity of catalase and superoxide dismutase (SOD)
in parallel with the decrease in reactive oxygen species levels in
cardiomyocytes. We observed that SN evoked the activation of all of the AMPK,
P38/MAPK and ERK/MAPK pathways in cardiomyocytes, but pretreatment with only AMPK
inhibitor (compound C) and ERK1/2/MAPK inhibitor (PD98059) counteracted the
protective effects of SN against cardiomyocyte hypertrophy and the suppressive
effects of SN on oxidant stress in cardiomyocytes. These results indicated that
endogenous SN is induced in hypertrophic cardiomyocytes, and may play a
protective role in the pathogenesis of cardiac hypertrophy. These results suggest
that exogenous SN supplementation protects the cardiac hypertrophy induced by ISO
treatment through the activation of AMPK and ERK/MAPK pathways, thus upregulating
antioxidants and suppressing oxidative stress.
PMID- 29337196
TI - Nicorandil and theophylline can protect experimental rats against complete
Freund's adjuvant-induced rheumatoid arthritis through modulation of
JAK/STAT/RANKL signaling pathway.
AB - Signaling pathways are interesting fields of study of pathogenesis and treatment
trials. We elucidated the possible protective effects of nicorandil (15mg/kg/day)
and theophylline (20mg/kg/day) on experimentally-induced RA, focusing on the role
of JAK (Janus Kinase) / STAT (Signal Transducer and Activator of Transcription) /
RANKL (Receptor Activator of Nuclear factor-Kappa B Ligand) / cytokine signaling
pathway. Four sets of experiments were performed. First, effect of test agents on
normal animals was evaluated. Second, effect of test agents was evaluated on
Complete Freund's Adjuvant (CFA; 0.3ml, s.c.)-induced RA to investigate anti
arthritic effect. Third, effect of test agents was evaluated on growth hormone
(GH; 2mg/kg/day, s.c.)-induced stimulation of JAK/STAT/RANKL/cytokine signaling
pathway to investigate the role of this signaling pathway in their anti-arthritic
effect. Fourth, the effect of test agents was performed on CFA/GH-induced RA. To
fulfill this purpose, serum anti-citrullinated peptide antibody (ACPA),
interleukin-6 (IL-6), and cartilage oligomeric matrix protein (COMP), together
with tissue JAK2, STAT3, RANKL, inducible and endothelial nitric oxide synthases
(iNOS and eNOS) as well as macrophage inflammatory protein (MIP1alpha) were
estimated using ELISA, Western blotting and PCR techniques, confirmed by a
histopathological study. Test agents significantly corrected JAK2, STAT3, RANKL
and IL-6 values in animals receiving GH. Additionally, test agents could correct
ACPA, IL-6, COMP, JAK2, STAT3, RANKL, iNOS, eNOS and MIP1alpha levels compared
with the respective CFA or CFA/GH controls. These results conclude that
nicorandil and theophylline have good anti-arthritic effects related to
modulation of JAK/STAT/RANKL signaling pathway. Further clinical trials are
claimed.
PMID- 29337197
TI - Brain perfusion alterations in tick-borne encephalitis-preliminary report.
AB - BACKGROUND: Magnetic resonance imaging (MRI) changes in tick-borne encephalitis
(TBE) are non-specific and the pathophysiological mechanisms leading to their
formation remain unclear. This study investigated brain perfusion in TBE patients
using dynamic susceptibility-weighted contrast-enhanced magnetic resonance
perfusion imaging (DSC-MRI perfusion). METHODS: MRI scans were performed for 12
patients in the acute phase, 3-5days after the diagnosis of TBE. Conventional MRI
and DSC-MRI perfusion studies were performed. Cerebral blood flow (CBF), cerebral
blood volume (CBV), mean transit time (MTT), and time to peak (TTP) parametric
maps were created. The bilateral frontal, parietal, and temporal subcortical
regions and thalamus were selected as regions of interest. Perfusion parameters
of TBE patients were compared to those of a control group. RESULTS: There was a
slight increase in CBF and CBV, with significant prolongation of TTP in
subcortical areas in the study subjects, while MTT values were comparable to
those of the control group. A significant increase in thalamic CBF (p<0.001) and
increased CBV (p<0.05) were observed. Increased TTP and a slight reduction in MTT
were also observed within this area. CONCLUSIONS: The DSC-MRI perfusion study
showed that TBE patients had brain perfusion disturbances, expressed mainly in
the thalami. These results suggest that DSC-MRI perfusion may provide important
information regarding the areas affected in TBE patients.
PMID- 29337198
TI - Comparison of untagged and his-tagged dihydrodipicolinate synthase from the
enteric pathogen Vibrio cholerae.
AB - Given the emergence of multi drug resistant Vibrio cholerae strains, there is an
urgent need to characterize new anti-cholera targets. One such target is the
enzyme dihydrodipicolinate synthase (DHDPS; EC 4.3.3.7), which catalyzes the
first committed step in the diaminopimelate pathway. This pathway is responsible
for the production of two key metabolites in bacteria and plants, namely meso-2,6
diaminopimelate and L-lysine. Here, we report the cloning, expression and
purification of untagged and His-tagged recombinant DHDPS from V. cholerae (Vc
DHDPS) and provide comparative structural and kinetic analyses. Structural
studies employing circular dichroism spectroscopy and analytical
ultracentrifugation demonstrate that the recombinant enzymes are folded and exist
as dimers in solution. Kinetic analyses of untagged and His-tagged Vc-DHDPS show
that the enzymes are functional with specific activities of 75.6 U/mg and 112
U/mg, KM (pyruvate) of 0.14 mM and 0.15 mM, KM (L-aspartate-4-semialdehyde) of
0.08 mM and 0.09 mM, and kcat of 34 and 46 s-1, respectively. These results
demonstrate there are no significant changes in the structure and function of Vc
DHDPS upon the addition of an N-terminal His tag and, hence, the tagged
recombinant product is suitable for future studies, including screening for new
inhibitors as potential anti-cholera agents. Additionally, a polyclonal antibody
raised against untagged Vc-DHDPS is validated for specifically detecting
recombinant and native forms of the enzyme.
PMID- 29337199
TI - Designing an intuitive web application for drug discovery scientists.
AB - We discuss how we designed the Open Targets Platform (www.targetvalidation.org),
an intuitive application for bench scientists working in early drug discovery. To
meet the needs of our users, we applied lean user experience (UX) design methods:
we started engaging with users very early and carried out research, design and
evaluation activities within an iterative development process. We also emphasize
the collaborative nature of applying lean UX design, which we believe is a
foundation for success in this and many other scientific projects.
PMID- 29337200
TI - Mimicking the 3D biology of osteochondral tissue with microfluidic-based
solutions: breakthroughs towards boosting drug testing and discovery.
AB - The development of tissue-engineering (TE) solutions for osteochondral (OC)
regeneration has been slowed by technical hurdles related to the recapitulation
of their complex and hierarchical architecture. OC defects refer to damage of
both the articular cartilage and the underlying subchondral bone. To repair an OC
tissue defect, the complexity of the bone and cartilage must be considered. To
help achieve this, microfluidics is converging with TE approaches to provide new
treatment possibilities. Microfluidics uses precise micrometer-to-millimeter
scale fluid flows to achieve high-resolution and spatial and/or temporal control
of the cell microenvironment, providing powerful tools for cell culturing.
Herein, we overview the progress of microfluidics for developing 3D in vitro
models of OC tissue, with a focus on cancer bone metastasis.
PMID- 29337201
TI - On the glycosylation aspects of biosimilarity.
AB - The recent expiration of several protein therapeutics opened the door for
biosimilar development. Biosimilars are biologic medical products that are
similar but not identical copies of already-authorized protein therapeutics.
Critical quality attributes (CQA), such as post-translational modifications of
recombinant biotherapeutics, are important for the clinical efficacy and safety
of both the innovative biologics and their biosimilar counterparts. Here, we
summarize biosimilarity CQAs, considering the regulatory guidelines and the
statistical aspects (e.g., biosimilarity index) and then discuss glycosylation as
one of the important attributes of biosimilarity. Finally, we introduced the
'Glycosimilarity Index', which is based on the averaged biosimilarity criterion.
PMID- 29337202
TI - Progress with covalent small-molecule kinase inhibitors.
AB - With reduced risk of toxicity and high selectivity, covalent small-molecule
kinase inhibitors (CSKIs) have emerged rapidly. Through the lens of structural
system pharmacology, here we review this rapid progress by considering design
strategies and the challenges and opportunities offered by current CSKIs.
PMID- 29337203
TI - Stem cells as vehicles and targets of nanoparticles.
AB - Modulation of endogenous adult stem cell niches represents a promising strategy
for regeneration of tissues and to correct cell abnormalities, including cancer.
Recent advances show the possibility to target endogenous stem cells or their
progenies by using nanoparticles conjugated with specific biomolecules. In
addition, the targeting of the stem cell niche can be accomplished by using stem
cells loaded with nanoparticles. This review examines principles for the
targeting of endogenous stem cells as well as factors for the modulation of stem
cells.
PMID- 29337204
TI - The positive impacts of Real-World Data on the challenges facing the evolution of
biopharma.
AB - Demand for healthcare services is unprecedented. Society is struggling to afford
the cost. Pricing of biopharmaceutical products is under scrutiny, especially by
payers and Health Technology Assessment agencies. As we discuss here, rapidly
advancing technologies, such as Real-World Data (RWD), are being utilized to
increase understanding of disease. RWD, when captured and analyzed, produces the
Real-World Evidence (RWE) that underpins the economic case for innovative
medicines. Furthermore, RWD can inform the understanding of disease, help
identify new therapeutic intervention points, and improve the efficiency of
research and development (R&D), especially clinical trials. Pursuing
precompetitive collaborations to define shared requirements for the use of RWD
would equip service-providers with the specifications needed to implement cloud
based solutions for RWD acquisition, management and analysis. Only this approach
would deliver cost-effective solutions to an industry-wide problem.
PMID- 29337205
TI - Increasing mtDNA levels as therapy for mitochondrial optic neuropathies.
AB - Leber hereditary optic neuropathy (LHON) is a rare, inherited mitochondrial
disease. No treatment has shown a clear-cut benefit on a clinically meaningful
end-point. Primary open-angle glaucoma (POAG) is a frequent, acquired optic
neuropathy. Lowering intraocular pressure (IOP) reduces disease progression.
However, current methods to decelerate this progression are recognized as being
inadequate. Therefore, there is a clear need to look for new therapeutic
approaches. The growing evidence indicates that POAG can also be a mitochondrial
optic neuropathy (MON). Several risk elements are common for both diseases and
all of them decrease mitochondrial (mt)DNA content. Based on these susceptibility
factors and their molecular mechanism, we suggest herein pharmacological
therapies targeted to increase mtDNA levels, oxidative phosphorylation (OXPHOS)
capability, and mitochondrial energy production as treatments for MONs.
PMID- 29337206
TI - Evolution of the POU1F1 transcription factor in mammals: Rapid change of the
alternatively-spliced beta-domain.
AB - The POU1F1 (Pit-1) transcription factor is important in regulating expression of
growth hormone, prolactin and TSH beta-subunit, and controlling development of
the anterior pituitary cells in which these hormones are produced. POU1F1 is a
conserved protein comprising three main domains, an N-terminal transcription
activation domain (TAD), a POU-specific domain and a C-terminal homeodomain.
Within the TAD, a beta-domain can be inserted by alternative splicing, giving an
extended 'beta-variant' with altered properties. Here sequence data from over 100
species were used to assess the variability of POU1F1 in mammals. This showed
that the POU-specific domain and homeodomain are very strongly conserved, and
that the TAD is somewhat less conserved, as are linker and hinge regions between
these main domains. On the other hand, the beta-domain is very variable,
apparently evolving at a rate not significantly different from that expected for
unconstrained, neutral evolution. In several species stop and/or frameshift
mutations within the beta-domain would prevent expression of the beta-variant as
a functional protein. In most species expression of the beta-variant is low (<5%
of total POU1F1 expression). The rate of evolution of POU1F1 in mammals shows
little variation, though the lineage leading to dog does show an episode of
accelerated change. This comparative genomics study suggests that in most
mammalian species POU1F1 variants produced by alternative splicing may have
little physiological significance.
PMID- 29337207
TI - Intrasexual competition mediates the relationship between men's testosterone and
mate retention behavior.
AB - Previous research has established a link between testosterone concentrations in
males and their mating effort as it relates to their mate seeking behaviors.
However, very little research has analyzed how variability in basal testosterone
concentration of males affects their mating effort once they have secured a
romantic partner. In a sample of undergraduate men, the relationship between
testosterone, intrasexual competitiveness, and mate retention behavior was
examined. Results showed that higher basal testosterone predicted more self
reported mate retention effort. This relationship was mediated by intrasexual
competitiveness, such that high T men reported more intrasexual competitiveness,
which when included in the model predicted mate retention, and reduced the
initial T - mate retention relationship to statistical non-significance. When
examined separately, this mediation effect applied specifically to cost
inflicting, rather than benefit-provisioning, mate retention behavior. These are
the first findings to link T to mate retention effort and to identify intrasexual
competitiveness as a mechanism which might account for this relationship.
PMID- 29337208
TI - Quantum Mechanics predicts evolutionary biology.
AB - Nowhere are the shortcomings of conventional descriptive biology more evident
than in the literature on Quantum Biology. In the on-going effort to apply
Quantum Mechanics to evolutionary biology, merging Quantum Mechanics with the
fundamentals of evolution as the First Principles of Physiology-namely
negentropy, chemiosmosis and homeostasis-offers an authentic opportunity to
understand how and why physics constitutes the basic principles of biology.
Negentropy and chemiosmosis confer determinism on the unicell, whereas
homeostasis constitutes Free Will because it offers a probabilistic range of
physiologic set points. Similarly, on this basis several principles of Quantum
Mechanics also apply directly to biology. The Pauli Exclusion Principle is both
deterministic and probabilistic, whereas non-localization and the Heisenberg
Uncertainty Principle are both probabilistic, providing the long-sought after
ontologic and causal continuum from physics to biology and evolution as the
holistic integration recognized as consciousness for the first time.
PMID- 29337209
TI - The role of d-allo-isoleucine in the deposition of the anti-Leishmania peptide
bombinin H4 as revealed by 31P solid-state NMR, VCD spectroscopy, and MD
simulation.
AB - Bombinin H4 is an antimicrobial peptide that was isolated from the toad Bombina
variegata. Bombinin H family peptides are active against gram-positive, gram
negative bacteria, and fungi as well as the parasite Leishmania. Among them,
bombinin H4 (H4), which contains d-allo-isoleucine (d-allo-Ile) as the second
residue in its sequence, is the most active, and its l-isomer is bombinin H2
(H2). H4 has a significantly lower LC50 than H2 against Leishmania. However, the
atomic-level mechanism of the membrane interaction and higher activity of H4 has
not been clarified. In this work, we investigated the behavior of the
conformations and interactions of H2 and H4 with the Leishmania membrane using
31P solid-state nuclear magnetic resonance (NMR), vibrational circular dichroism
(VCD) spectroscopy, and molecular dynamics (MD) simulations. The generation of
isotropic 31P NMR signals depending on the peptide concentration indicated the
abilities of H2 and H4 to exert antimicrobial activity via membrane disruption.
The VCD experiment and density functional theory calculation confirmed the
different stability and conformations of the N-termini of H2 and H4. MD
simulations revealed that the N-terminus of H4 is more stable than that of H2 in
the membrane, in line with the VCD experiment data. VCD and MD analyses
demonstrated that the first l-Ile and second d-allo-Ile of H4 tend to take a cis
conformation. These residues function as an anchor and facilitate the easy
winding of the helical conformation of H4 in the membrane. It may assist to
quickly reach to the threshold concentration of H4 on the Leishmania membrane.
This article is part of a Special Issue entitled: d-Amino acids: biology in the
mirror, edited by Dr. Loredano Pollegioni, Dr. Jean-Pierre Mothet and Dr. Molla
Gianluca.
PMID- 29337210
TI - Rate of Urologic Injury with Robotic Hysterectomy.
AB - STUDY OBJECTIVE: To evaluate rates of urologic injury in patients who underwent
robotic hysterectomy compared with laparoscopic, vaginal, and open hysterectomy.
DESIGN: A retrospective analysis (Canadian Task Force classification II-2).
SETTING: Henry Ford Health System, 2013 to 2016. PATIENTS: Women who underwent
robotic, vaginal, laparoscopic, and open abdominal hysterectomy. INTERVENTIONS:
Robotic hysterectomy, laparoscopic-assisted vaginal hysterectomy, total
laparoscopic hysterectomy, laparoscopic supracervical hysterectomy, vaginal
hysterectomy, and abdominal hysterectomy. MEASUREMENTS AND MAIN RESULTS: To
identify patients with urologic injury, a departmental database for quality
improvement was searched for reported urologic injuries. In addition, patients
who had urology consultation within 90 days of hysterectomy were screened for
injury. A total of 3114 hysterectomies were identified by retrospective chart
review. One thousand eighty-eight robotic, 782 laparoscopic, 304 vaginal, and 940
abdominal hysterectomies were analyzed for urologic complications. A total of 27
injuries were confirmed (7 during laparoscopic hysterectomy, 10 during robotic
hysterectomy, 1 during vaginal hysterectomy, and 9 during abdominal
hysterectomy). The overall rate of urologic injury was 0.87% with a 0.55% risk of
bladder injury and a 0.32% risk of injury to the ureter. When the route of
hysterectomy was taken into account, the risk of urologic injury was 0.92% for
robotic hysterectomy, 0.90% for laparoscopic hysterectomy, 0.33% for vaginal
hysterectomy, and 0.96% for open hysterectomy. The mean body mass index (BMI) for
all patients was 32.7 kg/m2; injured patients had a mean BMI of 34.6 kg/m2, and
noninjured patients had a mean BMI of 32.0 kg/m2 (p = .10). CONCLUSION: Rates of
urologic injury with robotic hysterectomy are similar to those of laparoscopic
hysterectomy in our population. BMI was not significantly different in patients
who had urologic injuries. Surgeon volume was not associated with risk for
urologic injury.
PMID- 29337211
TI - Extraperitoneal Para-Aortic Lymphadenectomy by Robot-Assisted Laparoscopy.
AB - STUDY OBJECTIVE: To evaluate the outcomes of extraperitoneal para-aortic
lymphadenectomy by robot-assisted laparoscopy. DESIGN: A retrospective study
(Canadian Task Force classification III). SETTING: An academic institution.
PATIENTS: Twenty-three consecutive patients with gynecologic cancer who presented
for para-aortic lymphadenectomy between March 2016 and May 2017 were reviewed
retrospectively. INTERVENTIONS: Extraperitoneal para-aortic lymphadenectomy by
robot-assisted laparoscopy was performed. MEASUREMENTS AND MAIN RESULTS: Of the
23 patients reviewed retrospectively, 10 had cervical cancer, 7 had endometrial
cancer, 5 had adnexal cancer, and 1 had vaginal cancer. Data regarding patient
characteristics, indication for para-aortic lymphadenectomy, type of surgery
(infrarenal or inframesenteric), operative time, surgical complications, number
of nodes retrieved, and postoperative hospital length of stay were collected. Two
patients were excluded because of early perforation of the peritoneum. In total,
21 para-aortic lymphadenectomies were performed (16 infrarenal and 5
inframesenteric). The median skin-to-skin operating time of infrarenal
extraperitoneal para-aortic lymphadenectomy by robot-assisted laparoscopy was 170
minutes (range, 90-225 minutes), the median lymph node count was 18 (range, 11
38), and the median estimated blood loss was 50 mL (range, 10-600 mL). The median
skin-to-skin operating time of inframesenteric extraperitoneal para-aortic
lymphadenectomy by robot-assisted laparoscopy was 120 minutes (range, 90-220
minutes), the median lymph node count was 10 (range, 7-19), and the median
estimated blood loss was 30 mL (range, 10-100). Intraoperative complications
included 1 thermal lesion of the left genitofemoral nerve, 1 thermal lesion of
the left mesoureter (a ureteral stent was placed to avoid ureteric necrosis and
fistula without after effect), and 1 lesion of the inferior vena cava that was
sutured by robot-assisted laparoscopy. There were 2 additional cases of
perforation of the peritoneum that occurred in the infrarenal group. The median
hospital length of stay was 1 day (range, 0-7 days). Three patients were
readmitted for symptomatic lymphocysts. CONCLUSION: Extraperitoneal para-aortic
lymphadenectomy by robot-assisted laparoscopy provides good visualization of the
operative field without arm conflict. Still, perforation of the peritoneum and
symptomatic lymphocysts are a postoperative concern.
PMID- 29337212
TI - Successful Management of Heterotopic Intramural Pregnancy Leading to a Live Birth
of the Intrauterine Pregnancy.
PMID- 29337214
TI - Correction.
PMID- 29337213
TI - Military Surgeon Volume and Stress Incontinence Surgery Complications: A
Retrospective Cohort Study.
AB - STUDY OBJECTIVE: To compare 12-month postoperative complication rates in women
who underwent sling procedures by high-volume versus low-volume surgeons at US
military treatment facilities (MTFs). DESIGN: Retrospective cohort study
(Canadian Task Force classification II-2). SETTING: US MTFs. PATIENTS: Female
military beneficiaries enrolled in TRICARE. INTERVENTIONS: Sling surgery for
stress urinary incontinence between January 1, 2011 and December 31, 2012.
MEASUREMENTS AND MAIN RESULTS: The primary exposure was surgeon volume (high vs
low). Surgeon volume was categorized as high or low based on the number of slings
performed in the previous 2 years at US MTFs (January 1, 2009 to December 31,
2010). The primary outcome was a composite variable indicating at least 1
postoperative complication within 12 months. We used International Classification
of Diseases, 9th revision and Current Procedural Terminology codes to identify
postoperative complications that occurred in the 12 months after the index sling
procedure. During the study period 348 gynecologic and urologic surgeons
performed 1632 slings. The average patient age was 47.2 years. Based on our data
distribution we classified surgeons as high volume (>12 slings/2 years) or low
volume (<4 slings/2 years). High-volume surgeons operated on patients who were
older, more likely to have comorbidities, and more likely to receive concomitant
prolapse surgery. Using a cluster analysis the overall likelihood of at least 1
postoperative complication in 12 months for high-volume versus low-volume
surgeons was 48.4% versus 42.2% (adjusted odds ratio, 1.24; 95% confidence
interval, .99-1.54; p = .06). There were no differences between high- and low
volume surgeons in the rate of almost all other postoperative complications.
CONCLUSION: No significant differences in 12-month complication rates after sling
surgery, stratified by surgeon volume, were seen in a setting of overall low
volume military surgeons.
PMID- 29337215
TI - Anti-angiogenic effects of Qingdu granule on breast cancer through inhibiting
NFAT signaling pathway.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Qingdu granule (QDG), a traditional Chinese
herbal prescription, had anti-tumor effect on breast cancer. However the
underlying mechanism of QDG was unclear. THE AIM OF THIS STUDY: The present study
aimed to investigate whether QDG could inhibit angiogenesis of breast cancer via
acting on nuclear factor of activated T-cells (NFAT) signaling pathway. This was
implicated in human umbilical vein endothelial cells (HUVECs) in vitro and breast
cancer xenograft model in vivo. MATERIALS AND METHODS: The VEGF165 (15.58 ng/mL)
induced human umbilical vein endothelial cells (HUVECs) were treated with serum
samples containing tamoxifen (TAM), tacrolimus (FK506), or QDG with three
dosages. The migration and canalization capacities of HUVECs were evaluated by
transwell migration and tube formation assay. In 72 h-cultured HUVECs, The gene
expression, protein amount, and nuclear translocation of NFATc3 were measured.
The anti-tumor and anti-angiogenic effects of QDG in vivo were investigated in
breast cancer xenograft model. The serum VEGF levels, microvessel density, and
protein expressions (immunohistochemistry and western blot) of VEGF, VEGFR2 and
NFATc3 were detected. RESULTS: The results showed that, QDG significantly
inhibited HUVEC migration and tube formation. It downregulated NFATc3 gene
expression, decreased NFATc3 protein amount, and reduced the ratio of NFATc3
nuclear translocation in HUVECs. In breast cancer xenograft model, QDG treatment
significantly suppressed tumor growth, inhibited VEGF release, and decreased
microvessel density. QDG reduced protein expressions of VEGF, VEGFR2 and NFATc3.
CONCLUSION: The results suggested that QDG showed anti-angiogenic effects of
breast cancer both in vitro and in vivo. The mechanism might be partially
associated with inhibiting NFAT signaling pathway.
PMID- 29337216
TI - In vitro lung epithelial cell transport and anti-interleukin-8 releasing activity
of liposomal ciprofloxacin.
AB - As a promising long-acting inhaled formulation, liposomal ciprofloxacin (Lipo
CPFX) was characterized in the in vitro human lung epithelial Calu-3 cell
monolayer system, compared to ciprofloxacin in solution (CPFX). Its modulated
absorptive transport and uptake, and sustained inhibitory activity against
induced pro-inflammatory interleukin-8 (IL-8) release were examined. The
absorptive transport and uptake kinetics for Lipo-CPFX and CPFX were determined
at 0.1-50 mg/ml in the Transwell system. The Lipo-CPFX transport was then
challenged for mechanistic exploration via cell energy depletion, a reduced
temperature, endocytosis and/or lipid fusion inhibition, and addition of excess
non-loaded liposomes. The inhibitory activities of Lipo-CPFX and CPFX against
lipopolysaccharide (LPS)-induced IL-8 release were assessed in a co-incubation or
pre-incubation mode. In the tight Calu-3 cell monolayers, Lipo-CPFX yielded 15
times slower ciprofloxacin flux of absorptive transport and 5-times lower
cellular drug uptake than CPFX. Its transport appeared to be transcellular;
kinetically linear, proportional to encapsulated ciprofloxacin concentration; and
consistent with the cell energy-independent lipid bilayer fusion mechanism. Lipo
CPFX was equipotent to CPFX in the anti-IL-8 releasing activity upon 24 h co
incubation with LPS. Additionally, Lipo-CPFX, but not CPFX, retained the anti-IL
8 releasing activity even 24 h after pre-incubation. In conclusion, Lipo-CPFX
enabled slower absorptive lung epithelial cell transport and uptake of
ciprofloxacin, apparently via the lipid bilayer fusion mechanism, and the
sustained inhibitory activity against LPS-induced IL-8 release, compared to CPFX.
PMID- 29337217
TI - Peptide drug stability: The anti-inflammatory drugs Pep19-2.5 and Pep19-4LF in
cream formulation.
AB - In previous years, we developed anti-infective drugs based on antimicrobial
peptides (AMPs), which have been shown to effectively block severe infections and
inflammation in vitro as well as in vivo. Besides systemic application, the
occurrence of severe local infections necessitates a topical application for
example in the case of severe skin and soft tissue infections (SSTI). Recent
investigations show that the synthetic anti-lipopolysaccharide peptide (SALP)
Pep19-2.5 (Aspidasept(r) I) and a variant called Pep19-4LF (Aspidasept(r) II) are
able to supress inflammation reactions also in keratinocytes, Langerhans cells,
and dendritic cells from the skin. For topical application, a possible
formulation represents the drug dispersed into a pharmaceutical cream (DAC base
cream). Here, we present investigations on the stability of the peptides using
this formulation in dependence on time, which includes the evaluation of the
extraction procedure, the quantitative analysis of the peptides after extraction,
its sensitivity to protease degradation and its ability to maintain activity
against LPS-induced inflammation in vitro. We have developed an extraction
procedure for the peptides with an optimum yield and showed that Pep19-2.5 is
present as a dimer after extraction from the cream, whereas Pep19-4LF retains its
monomeric form. Both peptides show no degradation by chymotrypsin after
extraction for at least 1 h, which is indicative for an attachment of
constituents of the base cream, inhibiting the cutting into peptidic part
structures. The extracted peptides and in particular the dimeric Pep19-2.5 are
still able to inhibit the LPS-induced inflammation reaction in human mononuclear
cells.
PMID- 29337219
TI - Citrus bioflavonoid, hesperetin, as inhibitor of two thrombin-like snake venom
serine proteases isolated from Crotalus simus.
AB - Around 5.5 million people suffer from snakebites per year, with about 400,000
cases with some type of sequelae, such as amputation, and 20,000 to 125,000 cases
with the fatal end. Usually, the victim outcome depends on correct, agile and
many times in situ intervention based on the proper identification of the snake
venom type and its potential effects, among other factors. Therefore, knowledge
on the snake venom composition and a research on inhibitors of snake venom target
components might ameliorate envenoming dangerous outcome. Herein, two thrombin
like serine proteases from the Crotalus simus snake venom - SVSP1 and SVSP2 -
were isolated in two chromatographic steps, using gel filtration and then RP
HPLC. They showed molecular masses of around 31.3 and 24.6 kDa, respectively, and
mostly beta-sheet secondary structure features. The SVSP1 and SVSP2 were
sequenced using tandem mass spectrometry (Q-TOF). Using the known serine protease
structure (PDB entry: 4e7n), which was evaluated as homologous to the two target
proteins, in silico docking results showed that hesperetin is its excellent
inhibitor. Using in vitro tests with the commercial hesperetin, kinetic
parameters were obtained for SVSPs against the synthetic substrate BApNA.
Obtained results pointed that hesperetin might act as an uncompetitive (SVSP1) or
mixed (SVSP2) inhibitor. Also, the fluorescence quenching upon inhibition was
observed, as well as, red shift in maximums of around 20 nm, which indicate that
the tryptophan residues in the target enzymes suffered conformational changes
caused by hesperetin binding. Thus, a naturally occurring flavone that can easily
be extracted from oranges might serve as low-cost inhibitor of the investigated
snake venom proteases.
PMID- 29337218
TI - Calcium-dependent disorder-to-order transitions are central to the secretion and
folding of the CyaA toxin of Bordetella pertussis, the causative agent of
whooping cough.
AB - The adenylate cyclase toxin (CyaA) plays an essential role in the early stages of
respiratory tract colonization by Bordetella pertussis, the causative agent of
whooping cough. Once secreted, CyaA invades eukaryotic cells, leading to cell
death. The cell intoxication process involves a unique mechanism of translocation
of the CyaA catalytic domain directly across the plasma membrane of the target
cell. Herein, we review our recent results describing how calcium is involved in
several steps of this intoxication process. In conditions mimicking the low
calcium environment of the crowded bacterial cytosol, we show that the C
terminal, calcium-binding Repeat-in-ToXin (RTX) domain of CyaA, RD, is an
extended, intrinsically disordered polypeptide chain with a significant level of
local, secondary structure elements, appropriately sized for transport through
the narrow channel of the secretion system. Upon secretion, the high calcium
concentration in the extracellular milieu induces the refolding of RD, which
likely acts as a scaffold to favor the refolding of the upstream domains of the
full-length protein. Due to the presence of hydrophobic regions, CyaA is prone to
aggregate into multimeric forms in vitro, in the absence of a chaotropic agent.
We have recently defined the experimental conditions required for CyaA folding,
comprising both calcium binding and molecular confinement. These parameters are
critical for CyaA folding into a stable, monomeric and functional form. The
monomeric, calcium-loaded (holo) toxin exhibits efficient liposome
permeabilization and hemolytic activities in vitro, even in a fully calcium-free
environment. By contrast, the toxin requires sub-millimolar calcium
concentrations in solution to translocate its catalytic domain across the plasma
membrane, indicating that free calcium in solution is actively involved in the
CyaA toxin translocation process. Overall, this data demonstrates the remarkable
adaptation of bacterial RTX toxins to the diversity of calcium concentrations it
is exposed to in the successive environments encountered in the course of the
intoxication process.
PMID- 29337220
TI - BotAF, a new Buthus occitanus tunetanus scorpion toxin, produces potent analgesia
in rodents.
AB - This work reports the purification of new potent scorpion neuropeptide, named
BotAF, by an activity-guided screening approach. BotAF is a 64-residue long-chain
peptide that shares very high similarity with the original beta-like scorpion
toxin group, in which several peptides have been characterized to be anti
nociceptive in rodents. BotAF administration to rodents does not produce any
toxicity or motor impairment, including at high doses. In all models
investigated, BotAF turned out to be an efficient peptide in abolishing acute and
inflammatory (both somatic and visceral) pain in rodents. It performs with high
potency compared to standard analgesics tested in the same conditions. The anti
nociceptive activity of BotAF depends on the route of injection: it is inactive
when tested by i.c.v. or i.v. routes but gains in potency when pre-injected
locally (in the same compartment than the irritant itself) or by i.t. root 40 to
60 min before pain induction, respectively. BotAF is not an AINS-like compound as
it fails to reduce inflammatory edema. Also, it does not activate the opioidergic
system as its activity is not affected by naloxone. BotAF does also not bind onto
RyR and has low activity towards DRG ion channels (particularly TTX sensitive Na+
channels) and does not bind onto rat brain synaptosome receptors. In somatic and
visceral pain models, BotAF dose-dependently inhibited lumbar spinal cord c-fos/c
jun mRNA up regulation. Altogether, our data favor a spinal or peripheral anti
nociceptive mode of action of BotAF.
PMID- 29337221
TI - Venom characterization of the Amazonian scorpion Tityus metuendus.
AB - The soluble venom from the scorpion Tityus metuendus was characterized by various
methods. In vivo experiments with mice showed that it is lethal. Extended
electrophysiological recordings using seven sub-types of human voltage gated
sodium channels (hNav1.1 to 1.7) showed that it contains both alpha- and beta
scorpion toxin types. Fingerprint analysis by mass spectrometry identified over
200 distinct molecular mass components. At least 60 sub-fractions were recovered
from HPLC separation. Five purified peptides were sequenced by Edman degradation,
and their complete primary structures were determined. Additionally, three other
peptides have had their N-terminal amino acid sequences determined by Edman
degradation and reported. Mass spectrometry analysis of tryptic digestion of the
soluble venom permitted the identification of the amino acid sequence of 111
different peptides. Search for similarities of the sequences found indicated that
they probably are: sodium and potassium channel toxins, metalloproteinases,
hyaluronidases, endothelin and angiotensin-converting enzymes, bradykinin
potentiating peptide, hypothetical proteins, allergens, other enzymes, other
proteins and peptides.
PMID- 29337222
TI - Blockade of placental growth factor reduces vaso-occlusive complications in
murine models of sickle cell disease.
AB - Vaso-occlusive crisis (VOC) is the most common and debilitating complication of
sickle cell disease (SCD); recurrent episodes cause organ damage and contribute
to early mortality. Plasma placental growth factor (PlGF) levels are elevated in
SCD and can further increase under hypoxic conditions in SCD mice. Treatment with
a PlGF-neutralizing antibody (anti-PlGF Ab) in SCD mice reduced levels of
monocyte chemoattractant protein-3, eotaxin, macrophage colony-stimulating
factor, and plasminogen activator inhibitor-1 significantly, and of macrophage
derived chemokine and macrophage inflammatory protein-3beta moderately; this may
contribute to inhibition of leukocyte recruitment, activation, and thrombosis. In
subsequent experiments, anti-PlGF Ab treatment significantly reduced plasma
lactate dehydrogenase levels, indicating possible reduction in cellular
destruction and/or hemolysis. Histopathology studies revealed decreased incidence
and severity of congestion in the lungs and spleen with repeated anti-PlGF Ab
treatment. Furthermore, anti-PlGF Ab significantly reduced vaso-occlusion events
under hypoxic conditions in a modified dorsal skinfold chamber model in SCD mice.
Therefore, elevated PlGF levels may contribute to recruitment and activation of
leukocytes. This can subsequently lead to increased pathology of affected organs
in addition to mediating acute hypoxia/reoxygenation-triggered vaso-occlusion
under SCD conditions. Thus, targeting PlGF may offer a therapeutic approach to
reduce acute VOC and possibly alleviate long-term vascular complications in
patients with SCD.
PMID- 29337223
TI - Sequential Conditioning with Thiotepa in T Cell- Replete Hematopoietic Stem Cell
Transplantation for the Treatment of Refractory Hematologic Malignancies:
Comparison with Matched Related, Haplo-Mismatched, and Unrelated Donors.
AB - The results of conventional allogeneic stem cell transplantation (SCT) in
refractory hematologic malignancies are poor. Sequential strategies have shown
promising results in refractory acute myelogenous leukemia (AML), but have not
been validated in a haploidentical (Haplo) transplant setting. We have developed
a new sequential approach combining chemotherapy with broad antitumor activity
(thiotepa 10 mg/kg, etoposide 400 mg/m2, and cyclophosphamide 1600 mg/m2 from day
-15 to day -10), followed after 3 days of rest by a reduced-intensity
conditioning regimen (fludarabine 150 mg/m2, i.v. busulfan 6.4 mg/kg, and
thymoglobulin 5 mg/kg from day -6 to day -2). High-dose post-transplantation
cyclophosphamide was added in cases with Haplo donors. Seventy-two patients
(median age, 54 years) with a refractory hematologic malignancy (44 with acute
myelogenous leukemia, 7 with acute lymphoblastic leukemia, 15 with
myelodysplastic syndrome/myeloproliferative neoplasms, and 6 with lymphomas) were
included in this retrospective multicenter study. Donors were Haplo (n = 27),
matched related (MRD; n = 16), and unrelated (UD; n = 29). With a median follow
up of 21 months, the 2-year overall survival (OS) and event-free survival (EFS)
were 54.7% and 49.3%, respectively, in recipients of Haplo transplants, 49.2% and
43.8%, respectively, in recipients of MRD transplants, and 37.9% and 28%,
respectively, in recipients of UD transplants. Compared with UD, the outcomes
were improved in Haplo in terms of the incidences of acute grade II-IV graft
versus-host disease (GVHD) (11.1% versus 41.4%; P < .001) and GVHD-free, relapse
free survival (44.4 versus 10.3%; P = .022). These results support the safety and
efficacy of a thiotepa-based sequential approach in allogeneic SCT with a Haplo
donor with post-transplantation immune modulation. Thus, in patients with
refractory hematologic malignancies, there seems to be no benefit in searching
for a UD when a Haplo donor is readily available.
PMID- 29337224
TI - An experimental study for rapid detection and quantification of endodontic
microbiota following photo-activated disinfection via new multiplex real-time PCR
assay.
AB - BACKGROUND: The infected root canal system harbors one of the highest
accumulations of polymicrobial infections. Since the eradication of
endopathogenic microbiota is a major goal in endodontic infection therapy, photo
activated disinfection (PAD) can be used as an alternative therapeutic method in
endodontic treatment. Compared to cultivation-based approaches, molecular
techniques are more reliable for identifying microbial agents associated with
endodontic infections. The purpose of this study was to evaluate the ability of
designed multiplex real-time PCR protocol for the rapid detection and
quantification of six common microorganisms involved in endodontic infection
before and after the PAD. MATERIALS AND METHODS: Samples were taken from the root
canals of 50 patients with primary and secondary/persistent endodontic infections
using sterile paper points. PAD with toluidine blue O (TBO) plus diode laser was
performed on root canals. Resampling was then performed, and the samples were
transferred to transport medium. Then, six target microorganisms were detected
using multiplex real-time PCR before and after the PAD. RESULTS: Veillonella
parvula was found using multiplex real-time PCR to have the highest frequency
among samples collected before the PAD (29.4%), followed by Porphyromonas
gingivalis (23.1%), Aggregatibacter actinomycetemcomitans (13.6%), Actinomyces
naeslundii (13.0%), Enterococcus faecalis (11.5%), and Lactobacillus rhamnosus
(9.4%). After TBO-mediated PAD, P. gingivalis strains, the most resistance
microorganisms, were recovered in 41.7% of the samples using molecular approach
(P > 0.05). CONCLUSION: As the results shown, multiplex real-time PCR as an
accurate detection approach with high-throughput and TBO-mediated PAD as an
efficient antimicrobial strategy due to the significant reduction of the
endopathogenic count can be used for detection and treatment of microbiota
involved in infected root canals, respectively.
PMID- 29337225
TI - Bone, muscle, and metabolic parameters predict survival in patients with
synchronous bone metastases from lung cancers.
AB - BACKGROUND: Lung adenocarcinoma regularly induces bone metastases that are
responsible for impaired quality of life as well as significant morbidity,
including bone pain and fractures. We aimed at identifying whether bone and
metabolic biomarkers were associated with the prognosis of lung adenocarcinoma
patients with synchronous bone metastases. PATIENTS AND METHODS: POUMOS is a
prospective cohort of patients diagnosed with lung adenocarcinoma and synchronous
bone metastases. All patients underwent biopsy of bone metastases to confirm
diagnosis, including genotyping of oncogenic drivers such as EGFR and KRAS. Whole
body composition was assessed using DEXA scan. Serum levels of C-reactive
protein, HbA1C, calcaemia, sCTX, and DKK1 were also measured. RESULTS: Sixty four
patients, aged (mean +/- SD) 65 +/- 11 years, were included. Thirty-nine (61%)
patients had a good performance status (PS 0-1); 56% had >5 bone lesions, and 41%
a weight-bearing bone (femour or tibia) involvement. Median overall survival was
7 months. In multivariate analysis, HbA1c (HR = 1.69 [1.10-2.63] per 0.5%
decrease; p = .02), DKK1 (HR = 1.28 [1.01-1.61] per 10 ng/mL increase; p = .04),
and hypercalcaemia (HR = 2.83 [1.10-7.30]; p = .03) were independently associated
with poorer survival. In the subgroup of patients with DEXA, sarcopenia was also
associated with poorer survival (HR = 2.96, 95%CI [1.40-6.27]; p = .005).
CONCLUSIONS: In patients with lung adenocarcinoma and synchronous bone
metastases, bone, sarcopenia, and metabolic parameters were predictors of poor
overall survival independently of common prognostic factors. We suggest that, in
addition to oncological therapy, supportive treatment dedicated to bone
metastases, muscle wasting, and energy metabolism are essential to improve
prognosis.
PMID- 29337226
TI - GLP-1 signaling and alcohol-mediated behaviors; preclinical and clinical
evidence.
AB - Alcohol addiction, affecting approximately four percent of the population,
contributes significantly to the global burden of diseases and is a substantial
cost to the society. The neurochemical mechanisms regulating alcohol mediated
behaviors is complex and in more recent years a new physiological role of the gut
brain peptides, traditionally known to regulate appetite and food intake, have
been suggested. Indeed, regulators of alcohol-mediated behaviors. One of these
gut-brain peptides is the annorexigenic peptide glucagon-like peptide-1 (GLP-1),
Preclinical studies show that GLP-1 receptor activation, either by GLP-1 or
analogues, attenuate the ability of alcohol to activate the mesolimbic dopamine
system as well as decrease alcohol consumption and operant self-administration.
In further support for the endogenous GLP-1 system in addiction processes are the
experimental data showing that a GLP-1 receptor antagonist increases alcohol
intake. Moreover, GLP-1 receptor agonists prevent the ability of other addictive
drugs to activate the mesolimbic dopamine system. The number of clinical studies
is limited, but show i) that genetic variation in the GLP-1 receptor gene is
associated with alcohol addiction as well as increased alcohol infusion in
humans, ii) that plasma levels of GLP-1 are associated with the subjective
experience of cocaine and iii) that a GLP-1 receptor agonist reduces alcohol
intake in patients with type-2 diabetes mellitus. These experimental and clinical
studies raises the concern that clinically available GLP-1 receptor agonists
deserves to be tested as potential treatments of patients with addictive
disorders including alcohol addiction. This article is part of the Special Issue
entitled 'Metabolic Impairment as Risk Factors for Neurodegenerative Disorders.'
PMID- 29337228
TI - WITHDRAWN: Monitoring the prevalence of genetically modified (GM) maize in Iran
food products.
AB - This article has been withdrawn at the request of the author(s) and/or editor.
The Publisher apologizes for any inconvenience this may cause. The full Elsevier
Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our
business/policies/article-withdrawal.
PMID- 29337227
TI - Juvenile social defeat stress exposure persistently impairs social behaviors and
neurogenesis.
AB - Adverse juvenile experiences, including physical abuse, often have negative
health consequences later in life. We investigated the influence of social defeat
stress exposure as juveniles on neuropsychological behaviors, and the causal role
of glucocorticoids in abnormal behaviors and impairment of neurogenesis in mice
exposed to the stress. The juvenile (24-day-old) and adult (70-day-old) male
C57BL/6J mice were exposed to social defeat stress induced by an aggressive ICR
mouse. Social defeat stress exposure as juveniles, even for 1 day, induced
persistent social avoidance to the unfamiliar ICR mouse in the social interaction
test, but that was not observed in mice exposed to the stress as adults. Social
avoidance by the stress exposure as juveniles for 10 consecutive days was
observed, when the target mouse was not only unfamiliar ICR but also another
C57BL/J mouse, but not an absent or an anesthetized ICR mouse. The stress
exposure did not induce anxiety- and depression-like behaviors in spontaneous
locomotor activity, elevated plus-maze test, marble-burying test, forced swimming
test, or sucrose preference test. Serum corticosterone levels increased
immediately after the stress exposure. The hippocampal neurogenesis was
suppressed 1 day and 4 weeks after the stress exposure. Administration of
mifepristone, a glucocorticoid receptor antagonist, prior to each stress
exposure, blocked the persistent social avoidance and suppression of
neurogenesis. In conclusion, social avoidance induced by social defeat stress
exposure as juveniles are more persistent than that as adults. These social
avoidances are associated with suppression of hippocampal neurogenesis via
glucocorticoid receptors.
PMID- 29337229
TI - Protective effect of flavonoids from Cyclocarya paliurus leaves against carbon
tetrachloride-induced acute liver injury in mice.
AB - Cyclocarya paliurus (Batal.) Iljinskaja (C. paliurus), known locally as 'sweet
tea tree', is commonly cultivated in China. Flavonoids from Cyclocarya paliurus
(Batal.) Iljinskaja (FC) is reported to exhibit multiple biological effects,
including anti-inflammatory, anti-oxidant and anti-diabetic activities. However,
their influence on carbon tetrachloride (CCl4)-induced acute liver injury remains
unclear. This study was designed to investigate the hepatoprotective effect of
total flavonoids from C. paliurus leaves. Results revealed that flavonoids from
C. paliurus significantly decreased CCl4-induced elevation of activities of
aspartate transaminase (AST), alanine transaminase (ALT) and superoxide dismutase
(SOD) as well as the level of malondialdehyde (MDA), and markedly increased the
levels of SOD, total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH
Px) compared with the model group. Structures of mainly compounds were elucidated
by nuclear magnetic resonance (NMR), mass spectrometry (MS) spectroscopic and
chemical analyses. This study clearly shows that flavonoids from C. paliurus
exert a potent protective effect against CCl4-induced acute liver injury in mice.
Its hepatoprotective effect appears to be closely associated with its antioxidant
activity. The results indicated that flavonoids from C. paliurus leaves could be
considered as a potent food supplement in the prevention of acute liver injury.
PMID- 29337230
TI - Cholesterol modulates the liposome membrane fluidity and permeability for a
hydrophilic molecule.
AB - The effect of cholesterol (CHOL) content on the permeability and fluidity of
dipalmitoylphosphatidylcholine (DPPC) liposome membrane was investigated.
Liposomes encapsulating sulforhodamine B (SRB), a fluorescent dye, were prepared
by reverse phase evaporation technique (REV) at various DPPC:CHOL molar ratios
(from 100:0 to 100:100). The release kinetics of SRB was studied during 48 h in
buffer (pH 7.4) containing NaCl at 37 degrees C. The DPPC:CHOL formulations were
also characterized for their size, polydispersity index and morphology.
Increasing CHOL concentration induced an increase in the mean liposomes size
accompanying with a shape transition from irregular to nanosized, regular and
spherical vesicles. The release kinetics of SRB showed a biphasic pattern; the
release data was then analyzed using different mathematical models. On the
overall, the SRB release was governed by a non-Fickian diffusion during the first
period (0-10 h) while it followed a Fickian diffusion between 10 and 48 h.
Changes in DPPC liposome membrane fluidity of various batches (CHOL% 0, 10, 20,
30 and 100) were monitored by using 5- and 16 doxyl stearic acids (DSA) as spin
labels. CHOL induced a decrease in the bilayer fluidity. Concisely, CHOL
represents a critical component in modulating the release of hydrophilic
molecules from lipid vesicles.
PMID- 29337232
TI - DA Neurons Promote the Instigation and Maintenance of Effortful Responding: A
Commentary on Fischbach-Weiss, Reese, and Janak.
PMID- 29337231
TI - Apoptosis induction by Pleurotus sajor-caju (Fr.) Singer extracts on colorectal
cancer cell lines.
AB - Pleurotus sajor-caju (PSC) is an edible mushroom used in food supplements,
presenting antitumor properties through induction of cell death pathways. The PSC
potential against colorectal cancer was analyzed by exposing HCT116wt cells to
different PSC extracts. The PSC n-hexane extract (PSC-hex) showed the highest
cytotoxicity effect (IC50 value 0.05 mg/mL). The observed cytotoxicity was then
associated to apoptosis-promoting and cell cycle-arrest pathways. PSC-hex was
able to induce apoptosis related to breakdown of mitochondrial membrane potential
and ROS generation. The absence of cytotoxicity in HTC116-p53 and HTC116-Bax
cells, alongside with an increase in p53, Bax and Caspase-3 expression, and
decrease in Bcl-2 expression, supports that the pro-apoptotic effect is probably
induced through a p53 associated pathway. PSC-hex induced cell cycle arrest at
G2/M in HCT116wt without cytotoxicity in HTC116-p21 cells. These findings suggest
that a p21/p53 cell cycle regulation pathway is probably disrupted by compounds
present on PSC-hex. Identification of the major components was then performed
with ergosta-5,7,22-trien-3beta-ol representing 30.6% of total weight. In silico
docking studies of ergosta-5,7,22-trien-3beta against Bcl-2 were performed and
results show a credible interaction with the Bcl-2 hydrophobic cleft. The results
show that PSC-hex can be used as supplementary food for adjuvant therapy in
colorectal carcinoma.
PMID- 29337234
TI - Electrophysiological Activity Prior to Self-initiated Movements is Related to
Impulsive Personality Traits.
AB - Electrophysiological and neuroimaging studies suggest that our actions are
initiated by unconscious mental processes long before awareness of intention to
act. The time window between the awareness of the intention to move and the
movement onset, which normally permits to exert a conscious "veto" on the
impending action, is modulated by individual differences in trait impulsivity. In
particular, trait impulsive people show a delayed awareness of the intention to
act, probably exceeding the "point of no return", after which the action can no
longer be inhibited. In order to investigate if individual differences in the
"veto" interval might be explained by differences in the readiness potential (RP)
dynamics, nineteen healthy participants underwent an impulsivity trait assessment
using the Barratt Impulsiveness Scale (BIS-11) and performed a task based on
Libet's clock paradigm, during EEG recordings of pre-movement neural activity. We
observed a positive relationship between impulsive personality trait and motor
system excitability during the preparation of self-initiated movements. In
particular, the RP showed an earlier negative rising phase and a greater
amplitude, with the increasing of BIS-11 scores. Based on present results, we
conclude hypothesizing that trait impulsivity might be characterized by less
effective preparatory inhibition mechanisms, which have a fundamental role in the
control of behavior.
PMID- 29337233
TI - Tau Deficiency Down-Regulated Transcription Factor Orthodenticle Homeobox 2
Expression in the Dopaminergic Neurons in Ventral Tegmental Area and Caused No
Obvious Motor Deficits in Mice.
AB - Tau protein participates in microtubule stabilization, axonal transport, and
protein trafficking. Loss of normal tau function will exert a negative effect.
However, current knowledge on the impact of tau deficiency on the motor behavior
and related neurobiological changes is controversial. In this study, we examined
motor functions and analyzed several proteins implicated in the maintenance of
midbrain dopaminergic (DA) neurons (mDANs) function of adult and aged tau+/+,
tau+/-, tau-/- mice. We found tau deficiency could not induce significant motor
disorders. However, we discovered lower expression levels of transcription
factors Orthodenticle homeobox 2 (OTX2) of mDANs in older aged mice. Compared
with age-matched tau+/+ mice, there were 54.1% lower (p = 0.0192) OTX2 protein
(OTX2-fluorescence intensity) in VTA DA neurons of tau+/- mice and 43.6% lower (p
= 0.0249) OTX2 protein in VTA DA neurons of tau-/- mice at 18 months old.
Combined with the relevant reports, our results suggested that tau deficiency
alone might not be enough to mimic the pathology of Parkinson's disease. However,
OTX2 down-regulation indicates that mDANs of tau-deficient mice will be more
sensitive to toxic damage from MPTP.
PMID- 29337235
TI - Frequency-specific Effective Connectivity in Subjects with Cerebral Infarction as
Revealed by NIRS Method.
AB - A connectivity-based approach can highlight the network reorganization in the
chronic phases after stroke and contributes to the development of therapeutic
interventions. Using dynamic Bayesian inference, this study aimed to assess the
effective connectivity (EC) in various frequency bands through the near-infrared
spectroscopy (NIRS) method in subjects with cerebral infarction (CI). A phase
coupling model was established based on phase information extracted using the
wavelet transform of NIRS signals. Coupling strength and the main coupling
direction were estimated using dynamic Bayesian inference. Wilcoxon test and chi
square test were used to determine the significant difference in EC between two
groups. Results showed that the coupling strength of the EC in the CI group
significantly decreased relative to that in the healthy group. The decrease was
most significant in the frequency intervals IV (0.021 Hz-0.052 Hz; p = 0.0006)
and VI (0.005 Hz-0.095 Hz; p = 0.0028). The main coupling direction changed from
the right prefrontal cortex to the right motor cortex and left motor cortex in
the frequency intervals IV (p1 = 0.041, p2 = 0.047) and II (p1 = 0.0017, p2 =
0.0036), respectively. The EC decreased or was even lost significantly in the EC
map of the CI group. Experimental results indicated that information propagation
was blocked in the CI group than in the healthy group and resulted in the
decreased coupling strength and connectivity loss. The main coupling direction of
the motor section changed from driving into being driven because of the
degradation of limb movement function.
PMID- 29337237
TI - Uridine-5'-Triphosphate Partially Blocks Differentiation Signals and Favors a
more Repair State in Cultured rat Schwann Cells.
AB - Schwann cells (SCs) play a key role in peripheral nerve regeneration. After
damage, they respond acquiring a repair phenotype that allows them to
proliferate, migrate and redirect axonal growth. Previous studies have shown that
Uridine-5'-Triphosphate (UTP) and its purinergic receptors participate in several
pathophysiological responses in the nervous system. Our group has previously
described how UTP induces the migration of a Schwannoma cell line and promotes
wound healing. These data suggest that UTP participates in the signaling involved
in the regeneration process. In the present study we evaluated UTP effects in
isolated rat SCs and cocultures of SCs and dorsal root ganglia neurons. UTP
reduced cAMP-dependent Krox-20 induction in SCs. UTP also reduced the N-cadherin
re-expression that occurs when SCs and axons make contact. In myelinating
cocultures, a non-significant tendency to a lower expression of P0 and MAG
proteins in presence of UTP was observed. We also demonstrated that UTP induced
SC migration without affecting cell proliferation. Interestingly, UTP was found
to block neuregulin-induced phosphorylation of the ErbB3 receptor, a pathway
involved in the regeneration process. These results indicate that UTP could acts
as a brake to the differentiation signals, promoting a more migratory state in
the repair-SCs.
PMID- 29337236
TI - Maintenance of the Innate Seizure Threshold by Cyclooxygenase-2 is Not Influenced
by the Translational Silencer, T-cell Intracellular Antigen-1.
AB - Activity of neuronal cyclooxygenase-2 (COX-2), a primary source of PG synthesis
in the normal brain, is enhanced by excitatory neurotransmission and this is
thought to be involved in seizure suppression. Results herein showing that the
incidence of pentylenetetrazole (PTZ)-induced convulsions is suppressed in
transgenic mice overexpressing COX-2 in neurons support this notion. T-cell
intracellular antigen-1 (TIA-1) is an mRNA binding protein that is known to bind
to COX-2 mRNA and repress its translation in non-neuronal cell types. An
examination of the expression profile of TIA-1 protein in the normal brain
indicated that it is expressed broadly by neurons, including those that express
COX-2. However, whether TIA-1 regulates COX-2 protein levels in neurons is not
known. The purpose of this study was to test the possibility that deletion of TIA
1 increases basal COX-2 expression in neurons and consequently raises the seizure
threshold. Results demonstrate that neither the basal nor seizure-induced
expression profiles of COX-2 were altered in mice lacking a functional TIA-1 gene
suggesting that TIA-1 does not contribute to regulation of COX-2 protein
expression in neurons. The acute PTZ-induced seizure threshold was also unchanged
in mice lacking TIA-1 protein, indicating that this RNA binding protein does not
influence the innate seizure threshold. Nevertheless, the results raise the
possibility that the level of neuronal COX-2 expression may be a determinant of
the innate seizure threshold and suggest that a better understanding of the
regulation of COX-2 expression in the brain could provide new insight into the
molecular mechanisms that suppress seizure induction.
PMID- 29337238
TI - Advantages of the Alpha-lipoic Acid Association with Chlorpromazine in a Model of
Schizophrenia Induced by Ketamine in Rats: Behavioral and Oxidative Stress
evidences.
AB - Schizophrenia is a chronic mental disorder reported to compromise about 1% of the
world's population. Although its pathophysiological process is not completely
elucidated, evidence showing the presence of an oxidative imbalance has been
increasingly highlighted in the literature. Thus, the use of antioxidant
substances may be of importance for schizophrenia treatment. The objective of
this study was to evaluate the behavioral and oxidative alterations by the
combination of chlorpromazine (CP) and alpha-lipoic acid (ALA), a potent
antioxidant, in the ketamine (KET) model of schizophrenia in rats. Male Wistar
rats (200-300 g) were treated for 10 days with saline, CP or ALA alone or in
combination with CP previous to KET and the behavioral (open field, Y-maze and
PPI tests) and oxidative tests were performed on the last day of treatment. The
results showed that KET induced hyperlocomotion, impaired working memory and
decreased PPI. CP alone or in combination with ALA prevented KET-induced
behavioral effects. In addition, the administration of KET decreased GSH and
increased nitrite, lipid peroxidation and myeloperoxidase activity. CP alone or
combined with ALA prevented the oxidative alterations induced by KET. In
conclusion, the treatment with KET in rats induced behavioral impairments
accompanied by hippocampal oxidative alterations, possibly related to NMDA
receptors hypofunction. Besides that, CP alone or combined with ALA prevented
these effects, showing a beneficial activity as antipsychotic agents.
PMID- 29337239
TI - Background Suppression and its Relation to Foreground Processing of Speech Versus
Non-speech Streams.
AB - Since sound perception takes place against a background with a certain amount of
noise, both speech and non-speech processing involve extraction of target signals
and suppression of background noise. Previous works on early processing of speech
phonemes largely neglected how background noise is encoded and suppressed. This
study aimed to fill in this gap. We adopted an oddball paradigm where speech
(vowels) or non-speech stimuli (complex tones) were presented with or without a
background of amplitude-modulated noise and analyzed cortical responses related
to foreground stimulus processing, including mismatch negativity (MMN), N2b, and
P300, as well as neural representations of the background noise, that is,
auditory steady-state response (ASSR). We found that speech deviants elicited
later and weaker MMN, later N2b, and later P300 than non-speech ones, but N2b and
P300 had similar strength, suggesting more complex processing of certain acoustic
features in speech. Only for vowels, background noise enhanced N2b strength
relative to silence, suggesting an attention-related speech-specific process to
improve perception of foreground targets. In addition, noise suppression in
speech contexts, quantified by ASSR amplitude reduction after stimulus onset, was
lateralized towards the left hemisphere. The left-lateralized suppression
following N2b was associated with the N2b enhancement in noise for speech,
indicating that foreground processing may interact with background suppression,
particularly during speech processing. Together, our findings indicate that the
differences between perception of speech and non-speech sounds involve not only
the processing of target information in the foreground but also the suppression
of irrelevant aspects in the background.
PMID- 29337240
TI - Prevention of the Severity of Post-ischemic Inflammation and Brain Damage by
Simultaneous Knockdown of Toll-like Receptors 2 and 4.
AB - Toll-like receptor 2 (TLR2) and TLR4 belong to a family of highly conserved
pattern recognition receptors and are well-known upstream sensors of signaling
pathways of innate immunity. TLR2 and TLR4 upregulation is thought to be
associated with poor outcome in stroke patients. We currently show that transient
focal ischemia in adult rats induces TLR2 and TLR4 expression within hours and
shRNA-mediated knockdown of TLR2 and TLR4 alone and in combination decreases the
infarct size and swelling. We further show that TLR2 and TLR4 knockdown also
prevented the induction of their downstream signaling molecules MyD88, IRAK1, and
NFkappaB p65 as well as the pro-inflammatory cytokines IL-1beta, IL-6, and
TNFalpha. This study thus shows that attenuation of the severity of TLR2- and
TLR4-mediated post-stroke inflammation ameliorates ischemic brain damage.
PMID- 29337241
TI - Differential Effects of Alzheimer's Disease Abeta40 and 42 on Endocytosis and
Intraneuronal Trafficking.
AB - Anomalous neuronal accumulation of Abeta peptides was shown to affect synaptic
transmission and contribute to neurodegeneration in Alzheimer's disease (AD)
brain. Neuronal cells internalize amyloid beta (Abeta) peptides from the brain
extracellular space even under normal physiological conditions, and these
endocytotic pathways go awry during AD progression. We hypothesized that exposure
to toxic Abeta species accumulating in AD brain contributes to perturbations in
neuronal endocytosis. We have shown substantial down-regulation of KEGG
endocytotic pathway genes in AD patient brain regions that accumulate Abeta
compared to those in non-demented individuals. While both Abeta40 and Abeta42
perturbed endocytosis and intracellular trafficking in neuronal cells, Abeta40
had a greater effect than Abeta42. Moreover, Abeta40 decreased the neuronal
uptake and lysosomal accumulation of Abeta42, which tends to oligomerize at low
lysosomal pH. Hence, Abeta40 may reduce the prevalence of stable Abeta42
oligomers that are closely associated with neurodegeneration and are
intercellularly propagated across the vulnerable brain regions to eventually
nucleate as amyloid plaques. In conclusion, elevated brain Abeta levels and
Abeta42:40 ratio apparent in the early stages of AD could perturb intraneuronal
trafficking, augment the anomalous accumulation of amyloid peptides in AD brain,
and drive AD pathogenesis.
PMID- 29337242
TI - Expression of GAEC1 mRNA and protein and its association with clinical and
pathological parameters of patients with colorectal adenocarcinoma.
AB - AIM: GAEC1 (Gene amplified in esophageal cancer 1) is an oncogene with key
regulatory roles in the pathogenesis of oesophageal and colorectal carcinomas.
The aim of this study was to investigate expression profiles and
clinicopathological significance of GAEC1 mRNA and protein in patients with
colorectal carcinomas. METHOD: Matched cancer and non-cancer fresh frozen tissues
were prospectively collected from 80 patients diagnosed with colorectal
adenocarcinoma (39 men and 41 women). The tissues were sectioned for RNA
extraction and cDNA conversion and quantified by a real-time polymerase chain
reaction. GAEC1 protein expression was analysed by immunohistochemistry using a
custom made GAEC1 antibody. RESULT: GAEC1 mRNA was upregulated in majority (52%,
n=42/80) of the colorectal carcinomas when compared to the matched non-neoplastic
tissues. High expression of GAEC1 mRNA as correlated with patients of younger age
(p=0.008), with lower grade carcinoma (p=0.028), presence of synchronous
adenocarcinomas (p=0.034) and without any associated adenomas (p=0.047). In
addition, patients with high GAEC1 mRNA overexpression had a shorter survival
time. Furthermore, high GAEC1 protein expression was noted among patients having
perforated colorectal carcinoma (p=0.04). CONCLUSION: The high expression of
GAEC1 mRNA/protein as well as its correlation with multiple clinicopathological
characteristics in patients with colorectal carcinoma strongly suggests that
GAEC1 is a key regulator in the initiation of colorectal carcinogenesis.
PMID- 29337243
TI - Intratumoral morphological heterogeneity can be an indicator of genetic
heterogeneity in colorectal cancer.
AB - Anti-EGFR-targeted therapy is used to treat metastatic colorectal cancers with
RAS wild-type. However, resistance to targeted therapy is often observed and can
be primary or acquired. One reason for primary resistance is the presence of
mutations that are undetected due to genetic heterogeneity, which can be
expressed by differences present in primary tumor and distant metastasis or
recurrence or by an intratumoral heterogeneity (presence of different subclones
in the investigated tumor sample). The aim of our study was to investigate if
morphological heterogeneity can be an indicator of intratumoral heterogeneity. We
analysed 13 samples with homogeneous and six samples with heterogeneous
morphology with NGS. We were able to demonstrate that intratumoral genetic
heterogeneity is present in all studied tumor samples, independent of homogeneous
or heterogeneous morphology. Moreover, one sample of our cohort with
morphological and genetic heterogeneity had a genetic wild-type profile in one
tumor component. Therefore, we recommend to include each morphologically
identifiable tumor component in the mutational analysis to not overlook
resistance-inducing or potentially targetable mutations.
PMID- 29337244
TI - MiR-142-5p act as an oncogenic microRNA in colorectal cancer: Clinicopathological
and functional insights.
AB - OBJECTIVES: miR-142-5p was noted aberrantly expressed and plays important roles
in different pathophysiological conditions in human. The present study aims to
examine the expression of miR-142-5p and its association with clinicopathological
factors in a large cohort of patients with colorectal cancer. In addition, the
cellular effects of miR-142-5p and its interacting targets in colon cancer cells
were investigated. METHODS: Expression of miR-142-5p in colorectal cancer tissues
(n=125) and colon cancer cell lines were analysed using real-time polymerase
chain reaction. In vitro assays (cell proliferation, wound healing and colony
formation) were used to study the miR-142-5p induced cellular effects. Western
blots were used to examine the modulation of FAM134B, KRAS, EPAS1 and KLF6
proteins expression followed by miR-142-5p expression-manipulation. RESULTS:
Significant high expression of miR-142-5p was noted in cancer tissues and cells
when compared to the controls (p<0.001). Overexpression of miR-142-5p in patients
with colorectal cancer was common (72%; 90/125). miR-142-5p overexpression was
associated with cancer in the proximal colorectum and with B-raf positive
patients (p=0.05). Exogenous overexpression of miR-142-5p resulted in
significantly increased cell proliferation, colony formation, and wound healing
capacities, whereas inhibition of endogenous miR-142-5p led reduced cancer growth
properties. The cellular effects of miR-142-5p were mediated by the modulation of
tumour suppressor KLF6 expression, as the expression of miR-142-5p and KLF6
protein are inversely correlated in colon cancer cells. CONCLUSION: High miR-142
5p expression was associated with the biological aggressiveness of cancer. Thus,
suppression of miR-142-5p could be a therapeutic strategy for patients with
colorectal cancers.
PMID- 29337246
TI - TLR3 gene in Japanese sea perch (Lateolabrax japonicus): Molecular cloning,
characterization and expression analysis after bacterial infection.
AB - Toll-like receptors (TLRs) play important roles in fish innate immune and are
involved in the defense process of bacteria invasion. In the present study, the
full-length cDNA of TLR3 from the sea perch, Lateolabrax japonicus, was cloned
and characterized. The full length of LjTLR3 cDNA was 3265 bp including an open
reading frame of 2679 bp encoding a peptide of 922 amino acids. Tissues
distribution analysis indicated that LjTLR3 showed a tissue-specific variation
with high expression in spleen, head-kidney and liver. In order to investigate
LjTLR3 functions against bacteria infection, the expression patterns of LjTLR3
after Vibrio harveyi and Streptococcus agalactiae challenge were detected by qRT
PCR, and the results showed that LjTLR3 was significant up-regulated after both
bacteria stimulation in head-kidney, spleen and liver in a time-depended manner.
Furthermore, the results by in situ hybridization experiments showed that
positive signals of LjTLR3 mRNA in infected spleen and head-kidney were more
numerous than that in the control group. In addition, intracellular localization
revealed that LjTLR3 is distributed in the cytoplasm. In summary, these findings
suggest that LjTLR3 was involved in the immune process under bacteria infection.
This study would benefit to further clarify the roles of fish TLRs in the immune
process and contribute to further study on enhancing disease resistance of L.
japonicus.
PMID- 29337245
TI - Hepatic alcohol dehydrogenase deficiency induces pancreatic injury in chronic
ethanol feeding model of deer mice.
AB - The single most common cause of chronic pancreatitis (CP, a serious inflammatory
disease) is chronic alcohol abuse, which impairs hepatic alcohol dehydrogenase
(ADH, a major ethanol oxidizing enzyme). Previously, we found ~5 fold greater
fatty acid ethyl esters (FAEEs), and injury in the pancreas of hepatic ADH
deficient (ADH-) vs. hepatic normal ADH (ADH+) deer mice fed 3.5g% ethanol via
liquid diet daily for two months. Therefore, progression of ethanol-induced
pancreatic injury was determined in ADH- deer mice fed ethanol for four months to
delineate the mechanism and metabolic basis of alcoholic chronic pancreatitis
(ACP). In addition to a substantially increased blood alcohol concentration and
plasma FAEEs, significant degenerative changes, including atrophy and loss of
acinar cells in some areas, ultrastructural changes evident by such features as
swelling and disintegration of endoplasmic reticulum (ER) cisternae and ER stress
were observed in the pancreas of ethanol-fed ADH- deer mice vs. ADH+ deer mice.
These changes are consistent with noted increases in pancreatic injury markers
(plasma lipase, pancreatic trypsinogen activation peptide, FAEE synthase and
cathepsin B) in ethanol-fed ADH- deer mice. Most importantly, an increased levels
of pancreatic glucose regulated protein (GRP) 78 (a prominent ER stress marker)
were found to be closely associated with increased phosphorylated eukaryotic
initiation factor (eIF) 2alpha signaling molecule in PKR-like ER kinase branch of
unfolded protein response (UPR) as compared to X box binding protein 1S and
activating transcription factor (ATF)6 - 50kDa protein of inositol requiring
enzyme 1alpha and ATF6 branches of UPR, respectively, in ethanol-fed ADH- vs.
ADH+ deer mice. These results along with findings on plasma FAEEs, and pancreatic
histology and injury markers suggest a metabolic basis of ethanol-induced
pancreatic injury, and provide new avenues to understand metabolic basis and
molecular mechanism of ACP.
PMID- 29337247
TI - Effects of dietary administration of fenugreek seeds on metabolic parameters and
immune status of gilthead seabream (Sparus aurata L.).
AB - Medical plants could be used as a prophylactic method in aquaculture because they
are considered safe and so very promising alternatives to the use of chemicals.
The aim of the present work was to examine the effects of dietary fenugreek
(Trigonella foenum graecum) seeds administered for 8 weeks on the metabolic and
immune status of gilthead seabream (Sparus aurata L.). Four experimental groups
were designated: one receiving a basal diet (control) and three fed powdered
fenugreek seeds incorporated in the fish feed at 1%, 5% and 10%. The results show
that significant decreases in aspartate aminotransferase, creatine kinase,
potassium and the albumin/globulin ratio were detected in the serum of fish fed
10% fenugreek compared with the values recorded in control fish. As regards the
immune status, fish fed the 5% supplemented diet had higher haemolytic complement
and peroxidase activities than the control fish whilst antiprotease activity was
higher in fish fed the 1% fenugreek level respect to control fish and the fish
fed the highest fenugreek supplementation rate. Interestingly, the results also
revealed a significant enhancement of most of the cellular immune parameters
studied, especially in fish fed the highest level of fenugreek (10%). However,
the bacteriostatic activity of serum against fish pathogenic and non-pathogenic
bacteria was non-affected to any significant extent in fish fed the supplemented
diets. Overall, the results suggest that the high level of dietary fenugreek
tested in this work (10%) did not negatively affect any of the metabolic
parameters measured in serum but increased some of them. In addition, the
inclusion of fenugreek seeds in the gilthead seabream diet at 5% or 10% improved
the humoral and cellular immune activities, respectively. Further studies are
needed to better understand the effects of this natural product, which may be
suitable for use as a feed additive in fish aquaculture.
PMID- 29337248
TI - Immunohistochemical characterization of epidermal dendritic-like cells in giant
mudskipper, Periophthalmodon schlosseri.
AB - Giant Mudskipper, Periophthalmodon schlosseri (Pallas, 1770), is euryhaline,
amphibious, and air-breathing fish. These fishes live in close association to
mangrove forests and often spend over 90% of time out of water, in adjacent
mudflats. They have developed morphological and physiological adaptations to
satisfy their unique lifestyles. The skin is the primary interface between the
body and the environment, and has a central role in host defence. The initiation
of immune responses to antigens in the vertebrate skin has often been attributed
to epidermal Langerhans'cells (LC) that are dendritic cells (DC), antigen
presenting cells (APC) which reside in the epidermis. Dendritic cells have been
characterized morphologically and functionally in the teleost fish tissues such
as rainbow trout, salmonids, medaka, African catfish and zebrafish. However,
there is no evidence of the presence of DCs and their role in mudskippers
immunity. The aim of this preliminary study was to characterize, through use of
specific antibodies: Toll-like receptor 2, S100, serotonin (5-HT), and Vesicular
acetylcholine transporter VAChT, a specific DC-like subpopulation in Pn.
schlosseri's epidermis.
PMID- 29337249
TI - Regulation of lactate dehydrogenase in response to WSSV infection in the shrimp
Litopenaeus vannamei.
AB - Lactate dehydrogenase (LDH) is key for anaerobic glycolysis. LDH is induced by
the hypoxia inducible factor -1 (HIF-1). HIF-1 induces genes involved in glucose
metabolism and regulates cellular oxygen homeostasis. HIF-1 is formed by a
regulatory alpha-subunit (HIF-1alpha) and a constitutive beta-subunit (HIF
1beta). The white spot syndrome virus (WSSV) induces anaerobic glycolysis in
shrimp hemocytes, associated with lactate accumulation. Although infection and
lactate production are associated, the LDH role in WSSV-infected shrimp has not
been examined. In this work, the effects of HIF-1 silencing on the expression of
two LDH subunits (LDHvan-1 and LDHvan-2) in shrimp infected with the WSSV were
studied. HIF-1alpha transcripts increased in gills, hepatopancreas, and muscle
after WSSV infection, while HIF-1beta remained constitutively expressed. The
expression for both LDH subunits increased in each tissue evaluated during the
WSSV infection, translating into increased enzyme activity. Glucose concentration
increased in each tissue evaluated, while lactate increased in gills and
hepatopancreas, but not in muscle. Silencing of HIF-1alpha blocked the increase
of LDH expression and enzyme activity, along with glucose (all tissues) and
lactate (gills and hepatopancreas) concentrations produced by WSSV infection.
These results demonstrate that HIF-1 up regulates the expression of LDH subunits
during WSSV infection, and that this induction contributes to substrate
metabolism in energetically active tissues of infected shrimp.
PMID- 29337250
TI - The STIM1 inhibitor ML9 disrupts basal autophagy in cardiomyocytes by decreasing
lysosome content.
AB - Stromal-interaction molecule 1 (STIM1)-mediated store-operated Ca2+ entry (SOCE)
plays a key role in mediating cardiomyocyte hypertrophy, both in vitro and in
vivo. Moreover, there is growing support for the contribution of SOCE to the Ca2+
overload associated with ischemia/reperfusion injury. Therefore, STIM1 inhibition
is proposed as a novel target for controlling both hypertrophy and
ischemia/reperfusion-induced Ca2+ overload. Our aim was to evaluate the effect of
ML9, a STIM1 inhibitor, on cardiomyocyte viability. ML9 was found to induce cell
death in cultured neonatal rat cardiomyocytes. Caspase-3 activation, apoptotic
index and release of the necrosis marker lactate dehydrogenase to the
extracellular medium were evaluated. ML9-induced cardiomyocyte death was not
associated with increased intracellular ROS or decreased ATP levels. Moreover,
treatment with ML9 significantly increased levels of the autophagy marker LC3-II,
without altering Beclin1 or p62 protein levels. However, treatment with ML9
followed by bafilomycin-A1 did not produce further increases in LC3-II content.
Furthermore, treatment with ML9 resulted in decreased LysoTracker(r) Green
staining. Collectively, these data suggest that ML9-induced cardiomyocyte death
is triggered by a ML9-dependent disruption of autophagic flux due to lysosomal
dysfunction.
PMID- 29337251
TI - Chromatin organization regulated by EZH2-mediated H3K27me3 is required for OPN
induced migration of bone marrow-derived mesenchymal stem cells.
AB - Osteopontin (OPN) is a chemokine-like extracellular matrix-associated protein
involved in the migration of bone marrow-derived mesenchymal stem cells (BMSCs).
An increasing number of studies have found that chromatin organization may affect
cellular migration. However, whether OPN regulates chromatin organization is not
understood, nor are the underlying molecular mechanisms. In this study, we
investigated the link between chromatin organization and BMSC migration and
demonstrated that OPN-mediated BMSC migration leads to elevated levels of
heterochromatin marker histone H3 lysine 27 trimethylation (H3K27me3) through the
methyltransferase EZH2. The expression of EZH2 reorganizes the chromatin
structure of BMSCs. Pharmacological inhibition or depletion of EZH2 blocks BMSC
migration. Moreover, using an atomic force microscope (AFM), we found that
chromatin decondensation alters the mechanical properties of the nucleus. In
addition, inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2)
signals represses OPN-promoted chromatin condensation and cell migration. Thus,
our results identify a mechanism by which ERK1/2 signalling drives specific
chromatin modifications in BMSCs, which alters chromatin organization and thereby
enables OPN-mediated BMSC migration.
PMID- 29337252
TI - Phosphatases catching up with the level of knowledge: Finally druggable?
PMID- 29337253
TI - Should standardized susceptibility testing for microbial biofilms be introduced
in clinical practice?
PMID- 29337254
TI - Are we living in an antibiotic resistance nightmare?
PMID- 29337255
TI - A comparative study of American and Chinese college students' motives for food
choice.
AB - Previous cross-cultural research has examined college students' food choice
decisions in different countries. The current study aimed to add to the
literature by examining similarities and differences in motives for food choice
between American (N = 328) and Chinese (N = 333) college students. The Food
Choice Questionnaire (FCQ) was used to measure the participants' motives for food
choice. Students' perceptions on the importance of diet and on their body
satisfaction were also obtained. Results show that, while there are many
similarities between the two cultural groups on the FCQ items, there are also
significant differences. Specifically, the two groups view sensory appeal,
weight, health, mood, and familiarity in a similar way, but the American
participants score higher on price and convenience whereas the Chinese score
higher on natural content and ethical concerns. We believe contextual cultural
factors of each country may be related to these results. Women view sensory
appeal and weight as significantly more important than men. Interactions between
culture and gender are also found. For example, American women score
significantly higher than American men on mood whereas there is no gender
difference in the Chinese group; on the other hand, Chinese men score
significantly higher on price than Chinese women whereas there is no gender
difference in the American group.
PMID- 29337256
TI - MicroRNA regulatory networks reflective of polyhexamethylene guanidine phosphate
induced fibrosis in A549 human alveolar adenocarcinoma cells.
AB - Polyhexamethylene guanidine phosphate (PHMG-phosphate), an active component of
humidifier disinfectant, is suspected to be a major cause of pulmonary fibrosis.
Fibrosis, induced by recurrent epithelial damage, is significantly affected by
epigenetic regulation, including microRNAs (miRNAs). The aim of this study was to
investigate the fibrogenic mechanisms of PHMG-phosphate through the profiling of
miRNAs and their target genes. A549 cells were treated with 0.75 MUg/mL PHMG
phosphate for 24 and 48 h and miRNA microarray expression analysis was conducted.
The putative mRNA targets of the miRNAs were identified and subjected to Gene
Ontology analysis. After exposure to PHMG-phosphate for 24 and 48 h, 46 and 33
miRNAs, respectively, showed a significant change in expression over 1.5-fold
compared with the control. The integrated analysis of miRNA and mRNA microarray
results revealed the putative targets that were prominently enriched were
associated with the epithelial-mesenchymal transition (EMT), cell cycle changes,
and apoptosis. The dose-dependent induction of EMT by PHMG-phosphate exposure was
confirmed by western blot. We identified 13 putative EMT-related targets that may
play a role in PHMG-phosphate-induced fibrosis according to the Comparative
Toxicogenomic Database. Our findings contribute to the comprehension of the
fibrogenic mechanism of PHMG-phosphate and will aid further study on PHMG
phosphate-induced toxicity.
PMID- 29337258
TI - Adding injury to infection: The relationship between injury status and genetic
diversity of Theileria infecting plains zebra, Equus quagga.
AB - Asymptomatic tick-borne infections are a common feature in wild herbivores. In
human-dominated habitats, snare injuries to wild herbivores are common and are
likely to co-occur with enzootic infections. The influence of injury on pattern,
course and outcome of enzootic infection in wild herbivores is unknown. We
identified Theileria species infecting zebra and assessed the relationship
between host injury-status and parasitaemia, parasite diversity and selection
regimes. We also determined host leucocyte differential as this can reveal
mechanisms by which injuries influence infections. Theileria infecting zebra was
identified using PCR and sequencing of the V4 region of the 18 s rRNA gene and
confirmed with phylogenetic analyses. The influence of injury status on parasite
infection patterns, genetic diversity and selection were assessed using
population genetic tools. Parasitaemia estimated from prevalence and leucocyte
differential were determined from microscopic examination of Giemsa stained thin
blood smears. Phylogenetic and sequence analyses revealed that the zebra
population studied was infected with three Theileria equi haplotypes.
Parasitaemia was lower among injured compared to non-injured animals and lower
during dry than wet season. Mean (+/-SD) genetic diversity was 0.386 (+/-0.128)
in injured and 0.513 (+/-0.144) in non-injured zebra (P = .549). Neutrality tests
indicated that T. equi is under strong purifying selection in injured females (Li
& Fu's D* = -2.037) and demographic expansion in all zebra during the wet season
(Tajima D = -1.904). Injured zebras had a higher median per cent of neutrophils
(64% vs 37%) a lower median per cent of basophils (0% vs 1%) and eosinophils (2%
vs 4.5%) than non-injured animals, suggesting a heightened immune response and a
shift from a Th2 to Th1 T-Cell response favoring the elimination of intracellular
parasites in injured animals. This study demonstrates the utility of population
genetics in revealing factors influencing parasite diversity and infection
patterns.
PMID- 29337257
TI - A comparison of the embryonic stem cell test and whole embryo culture assay
combined with the BeWo placental passage model for predicting the embryotoxicity
of azoles.
AB - In the present study, we show the value of combining toxico-dynamic and -kinetic
in vitro approaches for embryotoxicity testing of azoles. Both the whole embryo
culture (WEC) and the embryonic stem cells test (EST) predicted the in vivo
potency ranking of twelve tested azoles with moderate accuracy. Combining these
results with relative placental transfer rates (Papp values) as determined in the
BeWo cell culture model, increased the predictability of both WEC and EST, with
R2 values increasing from 0.51 to 0.87 and from 0.35 to 0.60, respectively. The
comparison of these in vitro systems correlated well (R2 = 0.67), correctly
identifying the in vivo strong and weak embryotoxicants. Evaluating also specific
gene responses related with the retinoic acid and sterol biosynthesis pathways,
which represent the toxicological and fungicidal mode of action of azoles
respectively in the WEC and EST, we observed that the differential regulation of
Dhrs3 and Msmo1 reached higher magnitudes in both systems compared to Cyp26a1 and
Cyp51. Establishing sensitive biomarkers across the in vitro systems for studying
the underlying mechanism of action of chemicals, such as azoles, is valuable for
comparing alternative in vitro models and for improving insight in the mechanism
of developmental toxicity of chemicals.
PMID- 29337259
TI - Mathematical modeling of tumor-induced immunosuppression by myeloid-derived
suppressor cells: Implications for therapeutic targeting strategies.
AB - Myeloid-derived suppressor cells (MDSCs) belong to immature myeloid cells that
are generated and accumulated during the tumor development. MDSCs strongly
suppress the anti-tumor immunity and provide conditions for tumor progression and
metastasis. In this study, we present a mathematical model based on ordinary
differential equations (ODE) to describe tumor-induced immunosuppression caused
by MDSCs. The model consists of four equations and incorporates tumor cells,
cytotoxic T cells (CTLs), natural killer (NK) cells and MDSCs. We also provide
simulation models that evaluate or predict the effects of anti-MDSC drugs (e.g.,
l-arginine and 5-Fluorouracil (5-FU)) on the tumor growth and the restoration of
anti-tumor immunity. The simulated results obtained using our model were in good
agreement with the corresponding experimental findings on the expansion of
splenic MDSCs, immunosuppressive effects of these cells at the tumor site and
effectiveness of l-arginine and 5-FU on the re-establishment of antitumor
immunity. Regarding this latter issue, our predictive simulation results
demonstrated that intermittent therapy with low-dose 5-FU alone could eradicate
the tumors irrespective of their origins and types. Furthermore, at the time of
tumor eradication, the number of CTLs prevailed over that of cancer cells and the
number of splenic MDSCs returned to the normal levels. Finally, our predictive
simulation results also showed that the addition of l-arginine supplementation to
the intermittent 5-FU therapy reduced the time of the tumor eradication and the
number of iterations for 5-FU treatment. Thus, the present mathematical model
provides important implications for designing new therapeutic strategies that aim
to restore antitumor immunity by targeting MDSCs.
PMID- 29337261
TI - Heart rate variability alters cardiac repolarization and electromechanical
dynamics.
AB - Heart rate continuously varies due to autonomic regulation, stochasticity in
pacemaking, and circadian rhythm, collectively termed heart rate variability
(HRV), during normal physiological conditions. Low HRV is clinically associated
with an elevated risk of cardiac arrhythmias. Alternans, a beat-to-beat
alternation in action potential duration (APD) and/or intracellular calcium (Ca)
transient, is a well-known risk factor associated with cardiac arrhythmias that
is typically studied under conditions of a constant pacing rate, i.e., the
absence of HRV. In this study, we investigate the effects of HRV on the interplay
between APD, Ca, and electromechanical properties, employing a nonlinear discrete
time map model that governs APD and intracellular Ca cycling with a stochastic
pacing period. We find that HRV can decrease variation in APD and peak Ca at fast
pacing rates for which alternans is present. Further, increased HRV typically
disrupts the alternating pattern for both APD and peak Ca and weakens the
correlation between APD and peak Ca, thus decoupling Ca-mediated instabilities
from repolarization alternation. We find that the efficacy of these effects is
regulated by the sarcoplasmic reticulum Ca uptake rate. Overall, these results
demonstrate that HRV disrupts arrhythmogenic alternans and suggests that HRV may
be a significant factor in preventing life-threatening arrhythmias.
PMID- 29337260
TI - Modelling and simulation of biased agonism dynamics at a G protein-coupled
receptor.
AB - Theoretical models of G protein-coupled receptor (GPCR) concentration-response
relationships often assume an agonist producing a single functional response via
a single active state of the receptor. These models have largely been analysed
assuming steady-state conditions. There is now much experimental evidence to
suggest that many GPCRs can exist in multiple receptor conformations and elicit
numerous functional responses, with ligands having the potential to activate
different signalling pathways to varying extents-a concept referred to as biased
agonism, functional selectivity or pluri-dimensional efficacy. Moreover, recent
experimental results indicate a clear possibility for time-dependent bias,
whereby an agonist's bias with respect to different pathways may vary
dynamically. Efforts towards understanding the implications of temporal bias by
characterising and quantifying ligand effects on multiple pathways will clearly
be aided by extending current equilibrium binding and biased activation models to
include G protein activation dynamics. Here, we present a new model of time
dependent biased agonism, based on ordinary differential equations for multiple
cubic ternary complex activation models with G protein cycle dynamics. This model
allows simulation and analysis of multi-pathway activation bias dynamics at a
single receptor for the first time, at the level of active G protein (alphaGTP),
towards the analysis of dynamic functional responses. The model is generally
applicable to systems with NG G proteins and N* active receptor states. Numerical
simulations for NG=N*=2 reveal new insights into the effects of system parameters
(including cooperativities, and ligand and receptor concentrations) on bias
dynamics, highlighting new phenomena including the dynamic inter-conversion of
bias direction. Further, we fit this model to 'wet' experimental data for two
competing G proteins (Gi and Gs) that become activated upon stimulation of the
adenosine A1 receptor with adenosine derivative compounds. Finally, we show that
our model can qualitatively describe the temporal dynamics of this competing G
protein activation.
PMID- 29337262
TI - Longitudinal patterns and response lengths of algae in riverine ecosystems: A
model analysis emphasising benthic-pelagic interactions.
AB - In riverine ecosystems primary production is principally possible in two
habitats: in the benthic layer by sessile algae and in the surface water by
planktonic algae being transported downstream. The relevance of these two
habitats generally changes along the rivers' continuum. However, analyses of the
interaction of algae in these two habitats and their controlling factors in
riverine ecosystems are, so far, very rare. We use a simplified advection
diffusion model system combined with ecological process kinetics to analyse the
interaction of benthic and planktonic algae and nutrients along idealised streams
and rivers at regional to large scales. Because many of the underlying processes
affecting algal dynamics are influenced by depth, we focus particularly on the
impact of river depth on this interaction. At constant environmental conditions
all state variables approach stable spatial equilibria along the river,
independent of the boundary conditions at the upstream end. Because our model is
very robust against changes of turbulent diffusion and stream velocity, these
spatial equilibria can be analysed by a simplified ordinary differential equation
(ode) version of our model. This model variant reveals that at shallower river
depths, phytoplankton can exist only when it is subsidised by detaching benthic
algae, and in turn, at deeper river depths, benthic algae can exist only in low
biomasses which are subsidised by sinking planktonic algae. We generalise the
spatial dynamics of the model system using different conditions at the upstream
end of the model, which mimic various natural or anthropogenic factors (pristine
source, dam, inflow of a waste water treatment plant, and dilution from e.g. a
tributary) and analyse how these scenarios influence different aspects of the
longitudinal spatial dynamics of the full spatial model: the relation of spatial
equilibrium to spatial maximum, the distance to the spatial maximum, and the
response length. Generally, our results imply that shallow systems recover within
significantly shorter distances from spatially distinct disturbances when
compared to deep systems, independent of the type of disturbance.
PMID- 29337263
TI - iMem-2LSAAC: A two-level model for discrimination of membrane proteins and their
types by extending the notion of SAAC into chou's pseudo amino acid composition.
AB - Membrane proteins execute significant roles in cellular processes of living
organisms, ranging from cell signaling to cell adhesion. As a major part of a
cell, the identification of membrane proteins and their functional types become a
challenging job in the field of bioinformatics and proteomics from last few
decades. Traditional experimental procedures are slightly applicable due to lack
of recognized structures, enormous time and space. In this regard, the demand for
fast, accurate and intelligent computational method is increased day by day. In
this paper, a two-tier intelligent automated predictor has been developed called
iMem-2LSAAC, which classifies protein sequence as membrane or non-membrane in
first-tier (phase1) and in case of membrane the second-tier (phase2) identifies
functional types of membrane protein. Quantitative attributes were extracted from
protein sequences by applying three discrete features extraction schemes namely
amino acid composition, pseudo amino acid composition and split amino acid
composition (SAAC). Various learning algorithms were investigated by using
jackknife test to select the best one for predictor. Experimental results
exhibited that the highest predictive outcomes were yielded by SVM in conjunction
with SAAC feature space on all examined datasets. The true classification rate of
iMem-2LSAAC predictor is significantly higher than that of other state-of- the-
art methods so far in the literature. Finally, it is expected that the proposed
predictor will provide a solid framework for the development of pharmaceutical
drug discovery and might be useful for researchers and academia.
PMID- 29337264
TI - Indirect reciprocity with negative assortment and limited information can promote
cooperation.
AB - Cooperation is ubiquitous in biological and social systems, even though
cooperative behavior is often costly and at risk of exploitation by non
cooperators. Several studies have demonstrated that indirect reciprocity, whereby
some members of a group observe the behaviors of their peers and use this
information to discriminate against previously uncooperative agents in the
future, can promote prosocial behavior. Some studies have shown that differential
propensities of interacting among and between different types of agents
(interaction assortment) can increase the effectiveness of indirect reciprocity.
No previous studies have, however, considered differential propensities of
observing the behaviors of different types of agents (information assortment).
Furthermore, most previous studies have assumed that discriminators possess
perfect information about others and incur no costs for gathering and storing
this information. Here, we (1) consider both interaction assortment and
information assortment, (2) assume discriminators have limited information about
others, and (3) introduce a cost for information gathering and storage, in order
to understand how the ability of discriminators to stabilize cooperation is
affected by these steps toward increased realism. We report the following
findings. First, cooperation can persist when agents preferentially interact with
agents of other types or when discriminators preferentially observe other
discriminators, even when they have limited information. Second, contrary to
intuition, increasing the amount of information available to discriminators can
exacerbate defection. Third, introducing costs of gathering and storing
information makes it more difficult for discriminators to stabilize cooperation.
Our study is one of only a few studies to date that show how negative interaction
assortment can promote cooperation and broadens the set of circumstances in which
it is know that cooperation can be maintained.
PMID- 29337265
TI - 99mTc-vinorelbine tartrate loaded spherulites: Lung disposition study in Sprague
Dawley rats by gamma scintigraphy.
AB - Vinorelbine Tartrate (VLB) is the first line chemotherapeutic agent for treatment
of Non-Small Cell Lung Cancer, whose non-specific distribution causes unwanted
side effects. The aim of the present investigation was to formulate VLB loaded
spherulites intended for targeting the lung. Spherulites were composed of
Soyabean Phosphatidylcholine (SPC), Cholesterol (Chol), Potassium oleate and
Mannitol. Lipid film prepared using SPC, Chol and Potassium oleate, was dispersed
in aqueous phase comprising Mannitol and VLB, followed by controlled shearing and
extrusion. PEGylated Spherulites were prepared by incorporating 1,2-distearoyl-sn
glycero-3 phosphatidylethanolamine-N-[methoxy poly (ethylene glycol)] (DSPE-PEG
2000) in the lipid phase. Vesicles were characterized for size, entrapment
efficiency and drug release. In vitro cell cytotoxicity and apoptosis study were
performed on A549 cell line. Radiolabeling of VLB was performed by direct
labeling with reduced technetium-99m. Binding affinity of 99mTc- labelled
complexes was assessed by diethylenetriaminepenta acetic acid (DTPA) challenge
test. Biodistribution study was done in Sprague Dawley rats. Dynamic light
scattering and Transmission electron micrographs confirmed that PEGylated and non
PEGylated Spherulites were discrete, spherical and exhibited the size range of
120-130 nm. Non-PEGylated and PEGylated Spherulites had an entrapment efficiency
of 95.65% and 94.2% respectively. In vitro drug release study indicated VLB plain
drug solution diffused completely within 24 h, however, Non-PEGylated and
PEGylated Spherulites showed similar release pattern till 48 h. Results of cell
line study showed that cells treated with VLB loaded Spherulites showed more
cytotoxicity and underwent high degree of apoptosis at lower concentration
compared to the VLB solution. Radiolabeled complex was stable in saline and
serum, further, DTPA challenge study ensured the high binding strength. Gamma
Scintigraphy displayed that PEGylated Spherulites were localized within lungs at
higher concentration than non-PEGylated followed by plain drug.
PMID- 29337266
TI - Comparison of the in vitro pharmacological profiles of long-acting muscarinic
antagonists in human bronchus.
AB - BACKGROUND AND PURPOSE: Long-acting muscarinic antagonists (LAMAs) have been
recommended for the treatment of chronic obstructive pulmonary disease and (more
recently) asthma. However, the in vitro pharmacological profiles of the four
LAMAs currently marketed (tiotropium, umeclidinium, aclidinium and
glycopyrronium) have not yet been compared (relative to ipratropium) by using the
same experimental approach. EXPERIMENTAL APPROACH: With a total of 560 human
bronchial rings, we investigated the antagonists' potency, onset and duration of
action for inhibition of the contractile response evoked by electrical field
stimulation. We also evaluated the antagonists' potency for inhibiting cumulative
concentration-contraction curves for acetylcholine and carbachol. KEY RESULTS:
The onset and duration of action were concentration-dependent. At submaximal,
equipotent concentrations, the antagonists' onsets of action were within the same
order of magnitude. However, the durations of action differed markedly. After
washout, ipratropium's inhibitory activity decreased rapidly (within 30-90 min)
but those of tiotropium and umeclidinium remained stable (at above 70%) for at
least 9 h. Aclidinium and glycopyrronium displayed less stable inhibitory
effects, with a progressive loss of inhibition at submaximal concentrations. In
contrast to ipratropium, all the LAMAs behaved as insurmountable antagonists by
decreasing the maximum responses to both acetylcholine and carbachol. CONCLUSIONS
AND IMPLICATIONS: The observed differences in the LAMAs' in vitro pharmacological
profiles in the human bronchus provide a compelling pharmacological rationale for
the differences in the drugs' respective recommended daily doses and frequencies
of administration.
PMID- 29337267
TI - Acute lung injury induced by intestinal ischemia and reperfusion is altered in
obese female mice.
AB - RATIONAL: Acute lung injury (ALI) is a common complication after intestinal
ischemia and reperfusion (I/R) injury that can lead to acute respiratory distress
syndrome (ARDS). We have previously demonstrated that females are protected
against lung damage induced by intestinal I/R through an estrogen mediated
mechanism. OBJECTIVES: To investigate the effect of obesity on ALI induced by
intestinal I/R in female mice. METHODS: C57Bl/6 female mice were fed with a
standard low-fat diet (SD) or a high-fat diet (HFD) for 9 weeks. Intestinal I/R
injury was induced by a 45 min occlusion of the mesenteric artery followed by 2
and 24 h of reperfusion. RESULTS: Significant increase in lung myeloperoxidase
expression (MPO) and neutrophil numbers of SD and HFD mice occurred at 2 h and 24
h of reperfusion. Furthermore, HFD mice presented a significant increase in lung
eosinophil peroxidase (EPO) expression and eosinophil numbers compared to SD
mice. Lung wet/dry weight ratio was significantly greater in HFD mice at 2 and 24
h of reperfusion, accompanied by a significant increase in the expression of
inducible NO in the lung tissue and a significant decrease in arterial oxygen
saturation at 24 h of reperfusion relative to SD mice. CONCLUSION: Obesity
predisposes female mice to increased pulmonary oedema and deterioration in gas
exchange, which is accompanied by an increase in iNOS expression in the lung.
PMID- 29337268
TI - The double-sidedness of cough in the elderly.
AB - Cough is a physiological reflex to protect airways against aspiration, but also
it is one of the most frequent problems that lead patients to seek medical care.
Chronic cough is more prevalent in the elderly than younger subjects, and more
challenging to manage due to frequent comorbidities and possible side effects
from drug treatment. Meanwhile, cough reflex does not decrease with natural aging
but is often impaired by pathologic conditions like stroke. The impairment in
cough reflex may lead to fatal complication like aspiration pneumonia. In this
paper, we reviewed epidemiology and clinical considerations for chronic cough in
the elderly, and summarized aging-related changes in cough reflex and also
possible ways to normalize cough reflex and prevent aspiration pneumonia.
PMID- 29337269
TI - Inhibitors of phosphodiesterases in the treatment of cough.
AB - A group of 11 enzyme families of metalophosphohydrolases called
phosphodiesterases (PDEs) is responsible for a hydrolysis of intracellular cAMP
and cGMP. Xanthine derivatives (methylxanthines) inhibit PDEs without selective
action on their single isoforms and lead to many pharmacological effects, e.g.
bronchodilation, anti-inflammatory and immunomodulating effects, and thus they
can modulate the cough reflex. Contrary, selective PDE inhibitors have been
developed to inhibit PDE isoforms with different pharmacological effects based on
their tissue expression. In this paper, effects of non-selective PDE inhibitors
(e.g. theophylline) are discussed, with a description of other putative
mechanisms in their effects on cough. Antitussive effects of selective inhibitors
of several PDE isoforms are reviewed, focusing on PDE1, PDE3, PDE4, PDE5 and
PDE7. The inhibition of PDEs suggests participation of bronchodilation,
suppression of TRPV channels and anti-inflammatory action in cough suppression.
Selective PDE3, PDE4 and PDE5 inhibitors have demonstrated the most significant
cough suppressive effects, confirming their benefits in chronic inflammatory
airway diseases associated with bronchoconstriction and cough.
PMID- 29337270
TI - The cationic tetradecapeptide mastoparan as a privileged structure for drug
discovery: Enhanced antimicrobial properties of mitoparan analogues modified at
position-14.
AB - Mastoparan (MP) peptides, distributed in insect venoms, induce a local
inflammatory response post envenomation. Most endogenous MPs share common
structural elements within a tetradecapeptide sequence that adopts an amphipathic
helix whilst traversing biological membranes and when bound to an intracellular
protein target. Rational modifications to increase cationic charge density and
amphipathic helicity engineered mitoparan (MitP), a mitochondriotoxic bioportide
and potent secretagogue. Following intracellular translocation, MitP is accreted
by mitochondria thus indicating additional utility as an antimicrobial agent.
Hence, the objectives of this study were to compare the antimicrobial activities
of a structurally diverse set of cationic cell penetrating peptides, including
both MP and MitP sequences, and to chemically engineer analogues of MitP for
potential therapeutic applications. Herein, we confirm that, like MP, MitP is a
privileged structure for the development of antimicrobial peptides active against
both prokaryotic and eukaryotic pathogens. Collectively, MitP and target
selective chimeric analogues are broad spectrum antibiotics, with the Gram
negative A. baumannii demonstrating particular susceptibility. Modifications of
MitP by amino acid substitution at position-14 produced peptides, Delta14MitP
analogues, with unique pharmacodynamic properties. One example, [Ser14]MitP,
lacks both cytotoxicity against human cell lines and mast cell secretory activity
yet retains selective activity against the encapsulated yeast C. neoformans.
PMID- 29337271
TI - RFRP-3, the mammalian ortholog of GnIH, induces cell cycle arrest at G2/M in
porcine ovarian granulosa cells.
AB - RFamide-related peptide-3 (RFRP-3), the mammalian ortholog of gonadotropin
inhibitory hormone (GnIH), has been proposed as a key inhibitory regulator of
mammal reproduction. Our previous studies have demonstrated that RFRP-3 inhibited
the expression of proliferation-related proteins in porcine granulose cells
(GCs), but the inhibitory mechanism causing this has not been discovered. Here,
we aim to elucidate the underlying mechanism and determine the cell cycle
regulatory sites of action of RFRP-3 on porcine GC proliferation. To this end,
the viability of porcine GCs was initially estimated by cell counting kit-8 (CCK
8). We confirmed that different doses of RFRP-3 decreased the cellular viability,
suggesting that RFRP-3 could inhibit the proliferation of GCs. Subsequently, we
evaluated the direct effects of RFRP-3 on the expression of cell cycle
regulators. Compared to the control treated cells, 10-6 and 10-8 M of RFRP-3
effectively reduced the transcription of Cyclin B1 and CDK1 mRNAs. However,
treatment with RFRP-3 did not alter Cyclin A2, Cyclin D1, CDK2, or CDK4 mRNA
levels. These results suggest that RFRP-3 might be inducing G2/M-phase arrest in
porcine GCs. Finally, to further determine the molecular mechanism underlying
RFRP-3-mediated G2/M cell cycle arrest, we observed the levels of G2/M cell cycle
regulatory factors in RFRP-3-treated porcine GCs. The results showed that RFRP-3
treatment significantly increased the expression of Myt1, p-Wee1 and p-Cdc2,
whereas the level of Cyclin B1 significantly decreased in porcine GCs treated
with 10-6 M of RFRP-3. Taken together, our data suggest that RFRP-3 regulates the
phosphorylation or expression of G2/M cell cycle regulatory factors to induce
G2/M-phase arrest via inhibition Cyclin B-CDK1 complex activation in porcine GCs,
which might provide an unfavorable condition for porcine GC proliferation.
PMID- 29337272
TI - Circulating adipokines and mRNA expression in adipose tissue and the placenta in
women with gestational diabetes mellitus.
AB - Maternal adipose tissue and the placenta secrete various molecules commonly
called adipokines such as chemerin, omentin-1, visfatin, adiponectin, and leptin
that are important players in the pathogenesis of insulin resistance. Gestational
diabetes mellitus (GDM) is defined as a state of glucose intolerance
characterized by beta-cell dysfunction and insulin resistance. To examine whether
circulating adipokines and their mRNA expression in the adipose tissue and the
placenta are altered in GDM pregnancy, we compared 15 GDM women [obese (BMI > 30)
and non-obese (BMI < 30)] to 23 NGT (normal glucose tolerance) women [obese and
non-obese], at the time of the Cesarean section. Circulating chemerin and leptin
were higher (p = 0.009 and p = 0.005, respectively) and circulating omentin-1,
visfatin, as well as the adiponectin/leptin ratio were lower (p = 0.039, p =
0.007 and p = 0.011, respectively) in GDM-obese compared to NGT-non-obese women.
Chemerin and leptin correlated positively with BMI and HOMA-IR and omentin-1
correlated negatively with BMI. Serum TNF-alpha was significantly elevated in all
obese compared to non-obese pregnant women and correlated positively with BMI.
Adiponectin levels were reduced -although not significantly- in GDM- and NGT
obese women compared to their non-obese counterparts. Resistin, RPB4 and IL-6
levels did not differ significantly between groups. Chemerin mRNA expression in
subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) was
significantly higher compared to placenta in all women (6-to 24-times, p < 0.05).
Chemerin-VAT mRNA expression in GDM-obese tended to be significantly higher
compared to NGT-non-obese women (3-times, p = 0.005). Omentin-1 mRNA expression
was significantly higher in VAT compared to SAT (50- to 100-times, p < 0.01) and
its expression in placenta was negligible in all women. Although, leptin was
expressed significantly higher in SAT compared to VAT and the placenta in all
women (5- to 46-times, p < 0.05), only its mRNA expression in VAT of obese (GDM
and NGT) differed significantly when compared to NGT-non-obese women (3-times
higher, p < 0.02). Visfatin mRNA expression was comparable in all tissues. In
conclusion, chemerin and leptin are elevated and omentin-1 and visfatin levels
are decreased in GDM women complicated by obesity. This finding together with the
positive association of chemerin and leptin with markers of insulin resistance,
suggests that these adipokines and more especially chemerin and leptin
accompanied by their adipose tissue expression could contribute to the increased
insulin resistance and low grade inflammation that characterizes GDM-obese women.
PMID- 29337273
TI - Identification of epistatic mutations and insights into the evolution of the
influenza virus using a mass-based protein phylogenetic approach.
AB - A mass-based protein phylogenetic approach developed in this laboratory has been
applied to study mutation trends and identify consecutive or near-consecutive
mutations typically associated with positive epistasis. While epistasis is
thought to occur commonly during the evolution of viruses, the extent of
epistasis in influenza, and its role in the evolution of immune escape and drug
resistant mutants, remains to be systematically investigated. Here putative
epistatic mutations within H3 hemagglutinin in type A influenza are identified
where leading parent mutations were found to predominate within reported
antigenic sites of the protein. Frequent subsequent mutations resided exclusively
in different antigenic regions, providing the virus with a possible immune escape
mechanism, or at other remote sites that drive beneficial protein structural and
functional change. The results also enable a "small steps" evolutionary model to
be proposed where the more frequent consecutive, or near-consecutive, non
conservative mutations exhibited less structural, and thus functional, change.
This favours the evolutionary survival of the virus over mutations associated
with more substantive change that may cause or risk its own extinction.
PMID- 29337274
TI - Species delimitation of the North American orchard-spider Leucauge venusta
(Walckenaer, 1841) (Araneae, Tetragnathidae).
AB - The orchard spider, Leucauge venusta (Walckenaer, 1841) is one of the most common
and abundant orb-weavers in North America. This species has a broad geographic
distribution extending across tropical and temperate regions of the Americas from
Canada to Brazil. Guided by a preliminary observation of the barcode gap between
sequences from specimens of L. venusta collected in Florida and other North
American localities, we collected across a transect through the southeastern USA
to investigate the observed genetic divide. The dataset, complemented with
additional samples from Mexico, and Brazil was analyzed for species delimitation
using STACEY and bGMYC based on sequences from one nuclear (ITS2) and one
mitochondrial marker (COI). The analyses clearly separate USA samples into two
deeply divergent and geographically structured groups (north-south) which we
interpret as two different species. We generated ecological niche models for
these two groups rejecting a niche equivalence hypothesis for these lineages.
Taxonomic changes are proposed based on these findings, Leucauge venusta is
restricted to denote the northern clade, and its known distribution restricted to
the USA. Leucauge argyrobapta (White, 1841) is removed from synonymy to denote
the populations in Florida, Mexico and Brazil. Although the delimitation analyses
suggest each of these geographic clusters within the L. argyrobapta samples
represent different species, more specimens from Central and South America are
needed to properly test the cohesion of L. argyrobapta populations.
PMID- 29337275
TI - The O-beta-linked N-acetylglucosaminylation of the Lamin B receptor and its
impact on DNA binding and phosphorylation.
AB - : Lamin B Receptor (LBR) is an integral protein of the interphase inner nuclear
membrane that is implicated in chromatin anchorage to the nuclear envelope.
Phosphorylation of a stretch of arginine-serine (RS) dipeptides in the amino
terminal nucleoplasmic domain of LBR regulates the interactions of the receptor
with other nuclear proteins, DNA and RNA and thus modulates tethering of
heterochromatin to the nuclear envelope. While phosphorylation has been
extensively studied, very little is known about other post-translational
modifications of the protein. There is only one report on the O-beta-linked N
acetyl-glucosaminylation (O-GlcNAcylation) of a serine residue downstream of the
RS domain of rat LBR. In the present study we identify additional O-GlcNAcylation
sites by using as substrates of O-beta-N-acetylglucosaminyltransferase (OGT) a
set of peptides containing the entire LBR RS domain or parts of it as well as
flanking sequences. The in vitro activity of OGT was assessed by tandem mass
spectrometry and NMR spectroscopy. Furthermore, we provide evidence that O
GlcNAcylation hampers DNA binding while it marginally affects RS domain
phosphorylation mediated by SRPK1, Akt2 and cdk1 kinases. GENERAL SIGNIFICANCE:
Our methodology providing a quantitative description of O-GlcNAc patterns based
on a combination of mass spectrometry and high resolution NMR spectroscopy on
short peptide substrates allows subsequent functional analyses. Hence, our
approach is of general interest to a wide audience of biologists aiming at
deciphering the functional role of O-GlcNAc glycosylation and its crosstalk with
phosphorylation.
PMID- 29337276
TI - Validation of diffusion MRI estimates of compartment size and volume fraction in
a biomimetic brain phantom using a human MRI scanner with 300 mT/m maximum
gradient strength.
AB - Diffusion microstructural imaging techniques have attracted great interest in the
last decade due to their ability to quantify axon diameter and volume fraction in
healthy and diseased human white matter. The estimates of compartment size and
volume fraction continue to be debated, in part due to the lack of a gold
standard for validation and quality control. In this work, we validate diffusion
MRI estimates of compartment size and volume fraction using a novel textile axon
("taxon") phantom constructed from hollow polypropylene yarns with distinct intra
and extra-taxonal compartments to mimic white matter in the brain. We acquired a
comprehensive set of diffusion MRI measurements in the phantom using multiple
gradient directions, diffusion times and gradient strengths on a human MRI
scanner equipped with maximum gradient strength (Gmax) of 300 mT/m. We obtained
estimates of compartment size and restricted volume fraction through a
straightforward extension of the AxCaliber/ActiveAx frameworks that enables
estimation of mean compartment size in fiber bundles of arbitrary orientation.
The voxel-wise taxon diameter estimates of 12.2 +/- 0.9 MUm were close to the
manufactured inner diameter of 11.8 +/- 1.2 MUm with Gmax = 300 mT/m. The
estimated restricted volume fraction demonstrated an expected decrease along the
length of the fiber bundles in accordance with the known construction of the
phantom. When Gmax was restricted to 80 mT/m, the taxon diameter was
overestimated, and the estimates for taxon diameter and packing density showed
greater uncertainty compared to data with Gmax = 300 mT/m. In conclusion, the
compartment size and volume fraction estimates resulting from diffusion
measurements on a human scanner were validated against ground truth in a phantom
mimicking human white matter, providing confidence that this method can yield
accurate estimates of parameters in simplified but realistic microstructural
environments. Our work also demonstrates the importance of a biologically
analogous phantom that can be applied to validate a variety of diffusion
microstructural imaging methods in human scanners and be used for standardization
of diffusion MRI protocols for neuroimaging research.
PMID- 29337277
TI - Compensatory dopaminergic-cholinergic interactions in conflict processing:
Evidence from patients with Parkinson's disease.
AB - Executive functions are complex both in the cognitive operations involved and in
the neural structures and functions that support those operations. This
complexity makes executive function highly vulnerable to the detrimental effects
of aging, brain injury, and disease, but may also open paths to compensation.
Neural compensation is often used to explain findings of additional or altered
patterns of brain activations by older adults or patient populations compared to
young adults or healthy controls, especially when associated with relatively
preserved performance. Here we test the hypothesis of an alternative form of
compensation, between different neuromodulator systems. 135 patients with
Parkinson's Disease (PD) completed vesicular monoamine transporter type2 (VMAT2)
and acetylcholinesterase PET scanning to assess the integrity of nigrostriatal
dopaminergic, thalamic cholinergic, and cortical cholinergic pathways, and a
behavioral test (Stroop + task-switching) that puts high demands on conflict
processing, an important aspect of executive control. Supporting the compensatory
hypothesis, regression models controlling for age and other covariates revealed
an interaction between caudate dopamine and cortical cholinergic integrity:
Cortical cholinergic integrity was a stronger predictor of conflict processing in
patients with relatively low caudate dopaminergic function. These results suggest
that although frontostriatal dopaminergic function plays a central role in
executive control, cholinergic systems may also make an important contribution.
The present results suggest potential pathways for remediation, and that the
appropriate interventions for each patient may depend on their particular profile
of decline. Furthermore, they help to elucidate the brain systems that underlie
executive control, which may be important for understanding other disorders as
well as executive function in healthy adults.
PMID- 29337278
TI - Effects of hunger state on the brain responses to food cues across the life span.
AB - The abundant exposure to food cues in our environment is one of the main drivers
of overconsumption. Food evaluation is important for the regulation of food
intake by the brain and it's interaction with hunger state. Children are
especially susceptible to food cues. Understanding the mechanisms behind this
regulation in healthy individuals across the life span can help to elucidate the
mechanisms underlying overconsumption and aid the development of future obesity
prevention strategies. Few functional neuroimaging studies have been done in
children and elderly. Furthermore, it is unknown how hunger state affects neural
food cue reactivity in these groups, since this has not been examined
consistently. We examined the effects of hunger state and age on the brain
responses to low- and high calorie foods. On two mornings, 122 participants (17
children; 38 teens; 36 adults; 31 elderly) performed a food image viewing task
while being scanned using fMRI, either fasted or sated. Hunger induced greater
activation during high versus low calorie food image viewing than satiety in the
bilateral dorsomedial (dmPFC) and in the right dorsolateral prefrontal cortex
(dlPFC) across all age groups. There was no significant main effect of age group
on high versus low calorie food image viewing and no interaction between age
group and hunger state. The greater activation of the dlPFC across all age groups
during high calorie food image viewing in a fasted state might reflect increased
inhibitory control in response to these foods. This may underlie the ability to
resist overconsumption of high calorie foods. Furthermore, increased medial
prefrontal cortex activation during hunger might reflect increased reward value
of high calorie foods, which declines with satiation. Further studies are needed
to better understand these results. Notably, overweight and obese individuals
should be included to examine whether these responses are altered by weight
status across the life span.
PMID- 29337279
TI - Suprathreshold fiber cluster statistics: Leveraging white matter geometry to
enhance tractography statistical analysis.
AB - This work presents a suprathreshold fiber cluster (STFC) method that leverages
the whole brain fiber geometry to enhance statistical group difference analyses.
The proposed method consists of 1) a well-established study-specific data-driven
tractography parcellation to obtain white matter tract parcels and 2) a newly
proposed nonparametric, permutation-test-based STFC method to identify
significant differences between study populations. The basic idea of our method
is that a white matter parcel's neighborhood (nearby parcels with similar white
matter anatomy) can support the parcel's statistical significance when correcting
for multiple comparisons. We propose an adaptive parcel neighborhood strategy to
allow suprathreshold fiber cluster formation that is robust to anatomically
varying inter-parcel distances. The method is demonstrated by application to a
multi-shell diffusion MRI dataset from 59 individuals, including 30 attention
deficit hyperactivity disorder patients and 29 healthy controls. Evaluations are
conducted using both synthetic and in-vivo data. The results indicate that the
STFC method gives greater sensitivity in finding group differences in white
matter tract parcels compared to several traditional multiple comparison
correction methods.
PMID- 29337281
TI - Clinical Significance of Early Fluid and Weight Change During Acute Heart Failure
Hospitalization.
AB - AIMS: To explore the association of changes in weight and fluid during treatment
for acute heart failure (AHF) with clinical endpoints. METHODS AND RESULTS:
Weight and net fluid changes recorded at 72-96 hours in 708 AHF patients enrolled
in Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart
Failure, Cardiorenal Rescue Study in Acute Decompensated Heart Failure, and Renal
Optimization Strategies Evaluation in Acute Heart Failure studies were compared
with freedom from congestion at 72-96 hours and a composite endpoint of death,
rehospitalization, and unplanned hospital visit at 60 days. Weight loss was
concordant with net fluid loss in 55%, discordant and less than expected for
fluid loss in 34%, and paradoxically discordant or more than expected for fluid
loss in 11% of patients. Weight loss, but not fluid loss, was associated with
freedom from congestion (odds ratio per 1-kg weight loss = 1.11 [1.03-1.19]) and
a nominal reduction in the composite endpoint (hazard ratio per 1-kg weight loss
= 0.98 [0.95-1.00]). Outcomes were similar in patients with concordant and
discordant weight-fluid loss. CONCLUSION: During treatment for AHF, early changes
in weight may be more useful for identifying response to therapy and for
predicting outcomes than net fluid output. Nearly one-half of patients receiving
decongestive therapies demonstrate discordant changes in weight and fluid;
however, discordance was not associated with outcomes.
PMID- 29337280
TI - Behavioral interventions for reducing head motion during MRI scans in children.
AB - A major limitation to structural and functional MRI (fMRI) scans is their
susceptibility to head motion artifacts. Even submillimeter movements can
systematically distort functional connectivity, morphometric, and diffusion
imaging results. In patient care, sedation is often used to minimize head motion,
but it incurs increased costs and risks. In research settings, sedation is
typically not an ethical option. Therefore, safe methods that reduce head motion
are critical for improving MRI quality, especially in high movement individuals
such as children and neuropsychiatric patients. We investigated the effects of
(1) viewing movies and (2) receiving real-time visual feedback about head
movement in 24 children (5-15 years old). Children completed fMRI scans during
which they viewed a fixation cross (i.e., rest) or a cartoon movie clip, and
during some of the scans they also received real-time visual feedback about head
motion. Head motion was significantly reduced during movie watching compared to
rest and when receiving feedback compared to receiving no feedback. However,
these results depended on age, such that the effects were largely driven by the
younger children. Children older than 10 years showed no significant benefit. We
also found that viewing movies significantly altered the functional connectivity
of fMRI data, suggesting that fMRI scans during movies cannot be equated to
standard resting-state fMRI scans. The implications of these results are twofold:
(1) given the reduction in head motion with behavioral interventions, these
methods should be tried first for all clinical and structural MRIs in lieu of
sedation; and (2) for fMRI research scans, these methods can reduce head motion
in certain groups, but investigators must keep in mind the effects on functional
MRI data.
PMID- 29337282
TI - Comparative proteome analysis of monolayer and spheroid culture of canine
osteosarcoma cells.
AB - : Osteosarcoma is an aggressive bone tumor with high metastasis rate in the lungs
and affects both humans and dogs in a similar way. Three-dimensional tumor cell
cultures mimic the in vivo situation of micro-tumors and metastases and are
therefore better experimental in vitro models than the often applied two
dimensional monolayer cultures. The aim of the present study was to perform
comparative proteomics of standard monolayer cultures of canine osteosarcoma
cells (D17) and three-dimensional spheroid cultures, to better characterize the
3D model before starting with experiments like migration assays. Using DIGE in
combination with MALDI-TOF/TOF we found 27 unique canine proteins differently
represented between these two culture systems, most of them being part of a
functional network including mainly chaperones, structural proteins, stress
related proteins, proteins of the glycolysis/gluconeogenesis pathway and
oxidoreductases. In monolayer cells, a noticeable shift to more acidic pI values
was noticed for several proteins of medium to high abundance; two proteins
(protein disulfide isomerase A3, stress-induced-phosphoprotein 1) showed an
increase of phosphorylated protein species. Protein distribution within the
cells, as detected by immunohistochemistry, displayed a switch of stress-induced
phosphoprotein 1 from the cytoplasm (in monolayer cultures) to the nucleus (in
spheroid cultures). Additionally, Western blot testing revealed upregulated
concentrations of metastasin (S100A4), triosephosphate isomerase 1 and septin 2
in spheroid cultures, in contrast to decreased concentrations of CCT2, a subunit
of the T-complex. Results indicate regulation of stress proteins in the process
of three-dimensional organization characterized by a hypoxic and nutrient
deficient environment comparable to tumor micro-metastases. SIGNIFICANCE:
Osteosarcoma is an aggressive bone tumor that early spreads to the lungs. Three
dimensional tumor cell cultures represent the avascular stage of micro-tumors and
metastases, and should therefore represent a better experimental in vitro model
compared to two-dimensional monolayer cultures. Significant differences have been
reported in response to drug and radiation treatment between these two culture
systems. A gel-based proteomic investigation was performed to compare protein
patterns of a canine osteosarcoma cell line cultivated under those two
conditions, to learn more about altered cell composition and its impact on cell
behaviour. Due to the fact that the canine osteosarcoma is an accepted model for
the human disease, results will be relevant for the human species as well.
PMID- 29337283
TI - Variability studies of allochthonous stone pine (Pinus pinea L.) plantations in
Chile through nut protein profiling.
AB - : Stone pine (Pinus pinea) is characterized by low differentiation of growth
parameters, high phenotypic plasticity and low genetic variability; detecting its
diversity in introduced Chilean populations is therefore relevant for
conservation and breeding programs. Here, variability among allochthonous Stone
pine populations in Chile was explored using electrophoresis-based proteomic
analysis of pine nuts. Cones from 30 populations distributed along a climatic
gradient in Chile were surveyed and sampled, and proteins were extracted from
seed flour using the TCA-acetone precipitation protocol. Extracts were subjected
to SDS-PAGE and 2-DE for protein resolution, gel images captured, and spot or
bands intensity quantified and subjected to statistical analysis (ANOVA,
unsupervised Hierarchical Analysis Clustering and PLS regression). Protein yield
ranged among populations from 161.7 (North populations) to 298.7 (South
populations) mg/g dry weight. A total of 50 bands were resolved by SDS-PAGE in
the 6.5-200 kDa Mr. range, of which 17 showed quantitative or qualitative
differences, with 12 proteins identified. Pine nut extracts from the most distant
populations were analyzed by 2-DE and a total of 129 differential spots were
observed, out of which 13 were proposed as putative protein markers of
variability. Out of the 129 spots, 118 proteins were identified after MALDI
TOF/TOF analysis. Identified proteins were classified into two principal
categories: reserve and stress related. We provide the first protein map of P.
pinea nuts. The use of a proteomic approach was useful to detect variability of
Stone pine across three Chilean macrozones, with correlations between protein
profiles and geoclimatic parameters, suggesting a new approach to study the
variability of this species. BIOLOGICAL SIGNIFICANCE: This study presents the
first protein map of Stone pine nuts, relevant for the advancement of protein
characterization in pine nuts. Putative protein markers are proposed, evidencing
that a proteomic approach may be useful to detect variability of Stone pine
across Chilean macrozones, suggesting a new approach to study the variability of
this species, which may also be extrapolated to other forest fruit species.
PMID- 29337284
TI - Method for identification of sensitive nodes in Boolean models of biological
networks.
AB - Biological systems are often represented as Boolean networks and analysed to
identify sensitive nodes which on perturbation disproportionately change a
predefined output. There exist different kinds of perturbation methods:
perturbation of function, perturbation of state and perturbation in update
scheme. Nodes may have defects in interpretation of the inputs from other nodes
and calculation of the node output. To simulate these defects and systematically
assess their effect on the system output, two new function perturbations,
referred to as 'not of function' and 'function of not', are introduced. In the
former, the inputs are assumed to be correctly interpreted but the output of the
update rule is perturbed; and in the latter, each input is perturbed but the
correct update rule is applied. These and previously used perturbation methods
were applied to two existing Boolean models, namely the human melanogenesis
signalling network and the fly segment polarity network. Through mathematical
simulations, it was found that these methods successfully identified nodes
earlier found to be sensitive using other methods, and were also able to identify
sensitive nodes which were previously unreported.
PMID- 29337285
TI - Comparison of clustering approaches with application to dual colour protein data.
AB - Cells communicate with their environment via proteins, located at the plasma
membrane separating the interior of a cell from its surroundings. The spatial
distribution of these proteins in the plasma membrane under different
physiological conditions is of importance, since this may influence their signal
transmission properties. In this study, the authors compare different methods
such as hierarchical clustering, extensible Markov models and the gammics method
for analysing such a spatial distribution. The methods are examined in a
simulation study to determine their optimal use. Afterwards, they analyse
experimental imaging data and extend these methods to simulate dual colour data.
PMID- 29337286
TI - Estimation of parameters for plasma glucose regulation in type-2 diabetics in
presence of meal.
AB - In this study, the authors propose a methodology for the estimation of glucose
masses in stomach (both in solid and liquid forms), intestine, plasma and tissue;
insulin masses in portal vein, liver, plasma and interstitial fluid using only
plasma glucose measurement. The proposed methodology fuses glucose-insulin
homoeostasis model (in the presence of meal intake) and plasma glucose
measurement with a Bayesian non-linear filter. Uncertainty of the model over
individual variations has been incorporated by adding process noise to the
homoeostasis model. The estimation is carried out over 24 h for the healthy
people as well as a type II diabetes mellitus patients. In simulation, the
estimator follows the truth accurately for both the cases. Moreover, the
performances of two non-linear filters, namely the unscented Kalman filter (KF)
and cubature quadrature KF are compared in terms of root mean square error. The
proposed methodology will be helpful in future to: (i) observe a patient's
insulin-glucose profile, (ii) calculate drug dose for any hyperglycaemic patients
and (iii) develop a closed-loop controller for automated insulin delivery system.
PMID- 29337287
TI - Revealing determinants of two-phase dynamics of P53 network under gamma
irradiation based on a reduced 2D relaxation oscillator model.
AB - This study proposes a two-dimensional (2D) oscillator model of p53 network, which
is derived via reducing the multidimensional two-phase dynamics model into a
model of ataxia telangiectasia mutated (ATM) and Wip1 variables, and studies the
impact of p53-regulators on cell fate decision. First, the authors identify a 6D
core oscillator module, then reduce this module into a 2D oscillator model while
preserving the qualitative behaviours. The introduced 2D model is shown to be an
excitable relaxation oscillator. This oscillator provides a mechanism that leads
diverse modes underpinning cell fate, each corresponding to a cell state. To
investigate the effects of p53 inhibitors and the intrinsic time delay of Wip1 on
the characteristics of oscillations, they introduce also a delay differential
equation version of the 2D oscillator. They observe that the suppression of p53
inhibitors decreases the amplitudes of p53 oscillation, though the suppression
increases the sustained level of p53. They identify Wip1 and P53DINP1 as possible
targets for cancer therapies considering their impact on the oscillator,
supported by biological findings. They model some mutations as critical changes
of the phase space characteristics. Possible cancer therapeutic strategies are
then proposed for preventing these mutations' effects using the phase space
approach.
PMID- 29337288
TI - Network-based method for detecting dysregulated pathways in glioblastoma cancer.
AB - The knowledge on the biological molecular mechanisms underlying cancer is
important for the precise diagnosis and treatment of cancer patients. Detecting
dysregulated pathways in cancer can provide insights into the mechanism of cancer
and help to detect novel drug targets. Based on the wide existing mutual
exclusivity among mutated genes and the interrelationship between gene mutations
and expression changes, this study presents a network-based method to detect the
dysregulated pathways from gene mutations and expression data of the glioblastoma
cancer. First, the authors construct a gene network based on mutual exclusivity
between each pair of genes and the interaction between gene mutations and
expression changes. Then they detect all complete subgraphs using CFinder
clustering algorithm in the constructed gene network. Next, the two gene sets
whose overlapping scores are above a specific threshold are merged. Finally, they
obtain two dysregulated pathways in which there are glioblastoma-related multiple
genes which are closely related to the two subtypes of glioblastoma. The results
show that one dysregulated pathway revolving around epidermal growth factor
receptor is likely to be associated with the primary subtype of glioblastoma, and
the other dysregulated pathway revolving around TP53 is likely to be associated
with the secondary subtype of glioblastoma.
PMID- 29337289
TI - Antioxidant activity of hydrated carboxylated nanodiamonds and its influence on
water gamma-radiolysis.
AB - Water radiolysis involves chemical decomposition of the water molecule into free
radicals after exposure to ionizing radiation. These free radicals have
deleterious effects on normal cell physiology. Carboxylated nanodiamonds (cNDs)
appear to modulate the deleterious effects of gamma-irradiation on the
pathophysiology of red blood cells (RBCs). In the present work, the antioxidant
activity of hydrated cNDs (h-cNDs) on limiting oxidative damage (the water
radiolysis effect) by gamma-irradiation was confirmed. Our results show that h
cNDs have remarkable free radical scavenging ability and preserve the enzymatic
activity of catalase after gamma-irradiation. The underlying mechanism through
which nanodiamonds exhibit antioxidant activity appears to depend on their
colloidal stability. This property of detonation synthesized nanodiamonds is
improved after carboxylation, which in turn influences changes in the hydrogen
bond strength in water. The observed stability of h-cNDs in water and their
antioxidant activity correlates with their protective effect on RBCs against
gamma-irradiation.
PMID- 29337290
TI - Threefold growth efficiency improvement of silica nanosprings by using silica
nanosprings as a substrate.
AB - The growth efficiency of one-dimension (1D) nanostructures via the vapor-liquid
solid process is commonly attributed to parameters such as precursor vapor
pressure, substrate temperature, and the choice of the catalyst. The work
presented herein is an investigation of the use of silica nanosprings (SNs) as a
3D substrate for improving the growth efficiency of SN themselves. SNs are a 1D
nanomaterial that form a nonwoven structure with optimal geometric
characteristics and surface properties that mitigate collisions between growing
nanosprings and ripening of the gold catalyst, which should improve SN yield.
Nanospring growth, for an eight hour period, on an SN coated surface relative to
an equivalent flat substrate increased from ~25 mgh-1 to ~80 mgh-1, respectively.
All things being equal, by splitting the typical amount of catalyst, in this case
gold, between the first and second growth, the double growth procedure produced
more than three times more nanosprings than the equivalent single growth of a SN.
In addition, using an SN as a substrate increased the sustained growth condition
from four to eight hours, and thus increased by a factor of ten the gravimetric
yield of SNs relative to the mass of gold used.
PMID- 29337291
TI - Realization of a half-metallic state on bilayer WSe2 using doping transition
metals (Cr, Mn, Fe, Co, Ni) in its interlayer.
AB - The structural, electronic and magnetic properties of Cr, Mn, Fe, Co and Ni-doped
bilayer WSe2 are predicted by using first principles calculations. The doped
transition-metal (TM) atoms show a covalent-binding with the nearest Se atoms.
The calculated electronic structures reveal that the TM Cr, Mn, Fe and Co-doped
bilayer WSe2 exhibits a half-metallic character with a 100% spin polarization at
the Fermi level, and the reason is ascribed to the strong hybridization peak
between the transition metals and the parent W and Se atoms. The Ni-doped bilayer
WSe2 is still a semiconductor with nonmagnetism. The Fe-doped system has a robust
stability of half-metallicity because there are three connected states peak
spanning the Fermi level. The doping of Cr, Mn, Fe and Co atoms leads to a
prominent total magnetism (0.93-3.65 [Formula: see text] moment per unit cell),
and an induced ~0.3 [Formula: see text] moment in parent W atoms is found in
addition to the main contribution of TM atomic magnetism (0.71-3.33 [Formula: see
text] moment per atom). The predicted Cr, Mn, Fe and Co-doped bilayer WSe2 should
be the candidate materials for spintronic devices due to their magnetic and half
metallic nature.
PMID- 29337292
TI - A rapid, ratiometric, enzyme-free, and sensitive single-step miRNA detection
using three-way junction based FRET probes.
AB - MicroRNAs (miRNAs) are single stranded endogenous molecules composed of only 18
24 nucleotides which are critical for gene expression regulating the translation
of messenger RNAs. Conventional methods based on enzyme-assisted nucleic acid
amplification techniques have many problems, such as easy contamination, high
cost, susceptibility to false amplification, and tendency to have sequence
mismatches. Here we report a rapid, ratiometric, enzyme-free, sensitive, and
highly selective single-step miRNA detection using three-way junction assembled
(or self-assembled) FRET probes. The developed strategy can be operated within
the linear range from subnanomolar to hundred nanomolar concentrations of miRNAs.
In comparison with the traditional approaches, our method showed high sensitivity
for the miRNA detection and extreme selectivity for the efficient discrimination
of single-base mismatches. The results reveal that the strategy paved a new
avenue for the design of novel highly specific probes applicable in diagnostics
and potentially in microscopic imaging of miRNAs in real biological environments.
PMID- 29337293
TI - A-TEEMTM, a New Molecular Fingerprinting Technique: Simultaneous
Absorbance-Transmission and Fluorescence Excitation-Emission Matrix Method.
AB - We investigate the new simultaneous Absorbance-Transmission and fluorescence
Excitation-Emission Matrix method for rapid and effective characterization of the
varying components from a mixture. The Absorbance-Transmission and fluorescence
Excitation-Emission Matrix method uniquely facilitates correction of fluorescence
inner-filter effects to yield quantitative fluorescence spectral information that
is largely independent of component concentration. This is significant because it
allows one to effectively monitor quantitative component changes using
multivariate methods and to generate and evaluate spectral libraries.
We
present the use of this novel instrument in different fields: i.e. tracking
changes in complex mixtures including natural water, wine as well as monitoring
stability and aggregation of hormones for biotherapeutics.
.
PMID- 29337294
TI - Large Area Few Layers Hexagonal Boron Nitride Prepared by Quadrupole Field Aided
Exfoliation.
AB - A quadrupole electric field mediated exfoliation method is proposed to convert
micron sized hexagonal boron nitride (hBN) powders into few layers hexagonal
boron nitride nano-sheets (h-BNNS). Under the optimum conditions (400 Hz, 40 V,
32MUg/mL, sodium deoxycholate, TAE medium), the hBN powders (thickness > 200 nm,
horizontal scale ~ 10 MUm) are successfully exfoliated into 0.5-4 nm (1-10
layers) thick h-BNNS with the same horizontal scale. Dynamic laser scattering
(DLS) and atomic force microscope (AFM) statistics show that the yield is 47.6 %
(for the portion with the thickness of 0.5-6 nm), and all of the vertical sizes
are reduced to smaller than 18 nm (45 layers).
PMID- 29337295
TI - How to manipulate magnetic states of antiferromagnets.
AB - Antiferromagnetic materials, which have drawn considerable attention recently,
have fascinating features: they are robust against perturbation, produce no stray
fields, and exhibit ultrafast dynamics. Discerning how to efficiently manipulate
the magnetic state of an antiferromagnet is key to the development of
antiferromagnetic spintronics. In this review, we introduce four main methods
(magnetic, strain, electrical, and optical) to mediate the magnetic states and
elaborate on intrinsic origins of different antiferromagnetic materials. Magnetic
control includes a strong magnetic field, exchange bias, and field cooling, which
are traditional and basic. Strain control involves the magnetic anisotropy effect
or metamagnetic transition. Electrical control can be divided into two parts,
electric field and electric current, both of which are convenient for practical
applications. Optical control includes thermal and electronic excitation, an
inertia-driven mechanism, and terahertz laser control, with the potential for
ultrafast antiferromagnetic manipulation. This review sheds light on effective
usage of antiferromagnets and provides a new perspective on antiferromagnetic
spintronics.
PMID- 29337296
TI - Computer analysis of histopathological images for tumor grading.
AB - OBJECTIVE: We developed a new method that enables automatic and rapid assessment
of a tumor's proliferation index from immunohistochemically (IHC) stained
microscopic images. APPROACH: The method is based on computer-aided analysis of
images - color filtration pixel-by-pixel (CFPP method) of the whole
histopathological virtual slides. MAIN RESULTS: The method is simple, rapid, and
does not require the time consuming step of selecting manually areas of interest
nor the need for computationally complicated detection of hot-spots, both of
which attempt to emulate a pathologist's way of estimating a proliferation index.
We apply our method to a set of diffuse large B-cell lymphoma (DLBCL) slide
images. SIGNIFICANCE: By appropriate changes in the color filtration thresholds,
our method may be adapted to the analysis of other types of tumors. It may also
be adapted for analysis of microscopic images in neuropathology, like biopsies of
dystrophic muscles. Because of its simplicity and rapidity it may also be applied
for analysis of series of images to assess dynamics of image complexity in
network physiology.
PMID- 29337297
TI - 3D hierarchical Ag nanostructures formed on poly(acrylic acid) brushes grafted
graphene oxide as promising SERS substrates.
AB - In this study, in situ generation of Ag nanostructures with various morphology on
poly(acrylic acid) (PAA) brushes grafted onto graphene oxide (GO), for use as
substrates for surface-enhanced Raman scattering (SERS), is demonstrated. The
overall synthetic strategy involves the loading of Ag precursor ions ((Ag+ and
[Ag(NH3)2]+) onto PAA brush-grafted GO, followed by their in situ reduction to Ag
nanostructures of various morphology using a reducing agent (NaBH4 or ascorbic
acid). Novel 3D hierarchical flowerlike Ag nanostructures were obtained by using
AgNO3 as precursor and ascorbic acid as reducing agent. Using 4-aminothiophenol
as probe molecules, the as-prepared hierarchical Ag nanostructures exhibited
excellent SERS performance, providing enhancement factors of ~107.
PMID- 29337298
TI - Tuning the electrical transport of type II Weyl semimetal WTe2
nanodevices by Mo doping.
AB - We fabricated nanodevices of MoxW1-xTe2 (x =0,
0.07, 0.35) and conducted systematic comparative study of their electrical
transport. Magnetoresistance measurements show that Mo doping can significantly
suppress the mobility and magnetoresistance. The results for the analysis of two
band model (TBM) show that the doping of Mo does not break the carrier balance.
By Shubnikov-de Haas oscillations (SdHO) analysis, we found that Mo doping also
has a strong suppress on the quantum oscillation of the sample, and the higher
the ratio of Mo is, the fewer the pockets observed in our experiments are.
Furthermore, with the increase of Mo ratio, the effective mass of electron and
hole increases gradually, while the corresponding quantum mobility decreases
rapidly.
PMID- 29337299
TI - Comparison of acrylic polymer adhesive tapes and silicone optical grease in light
sharing detectors for positron emission tomography.
AB - Optical coupling is an important factor in detector design as it improves optical
photon transmission by mitigating internal reflections at light-sharing
boundaries. In this work we compare optical coupling materials, namely double
sided acrylic polymer tapes and silicone optical grease (SiG), in the context of
positron emission tomography. Four double-sided tapes from 3 M of varying
thicknesses (0.229 mm-1.016 mm) and adhesive materials ('100MP', 'A100', and
'GPA') were characterized with spectrophotometer measurements as well as
photopeak amplitude and energy resolution measurements using lutetium-yttrium oxy
orthosilicate (LYSO) coupled to photomultiplier tubes (PMT) or silicon
photomultipliers (SiPMs). Transmission spectra from the spectrophotometer showed
over 80% transmission for all tapes at 420 nm and above, with 89.6% and 88.8%
transmission for the 0.508 mm and 1.016 mm thick GPA tapes, respectively, at 420
nm. Measurements with single-pixel LYSO-PMT and 4 * 4 array (one-to-one
coupled) LYSO-SiPM setups determined that SiG had the greatest photopeak
amplitude, with tapes showing 2.1%-14.8% reduction in photopeak amplitude with
respect to SiG. Energy resolution changed by less than 4% on a relative basis
between tapes and SiG with PMT measurements, however for the SiPM array
measurements the energy resolution improved from 15.6% +/- 2.7% full-width at
half-maximum to 11.4% +/- 1.2% for SiG and 1 mm GPA respectively. Data acquired
with dual-layer offset LYSO arrays (light sharing detector designs) demonstrated
that a detector coupled with 1 mm thick GPA tape produced equivalent detector
flood histograms to those from a design coupled with SiG and a 1 mm thick glass
lightguide. No significant degradation in photopeak amplitude and energy
resolution was observed over five months of measurements, indicating the tapes
maintain their coupling integrity over several months. Though minimal photopeak
amplitude degradation compared to SiG occurs, double-sided tapes are convenient
alternatives for optical coupling materials since they diffuse light
intrinsically, acting as a light guide, offer mechanical support and durability,
are easily applied and removed from scintillators/photodetectors, and are
relatively inexpensive and readily available.
PMID- 29337300
TI - Hydrodynamic shrinkage of liquid CO2 Taylor drops in a straight
microchannel.
AB - Hydrodynamic shrinkage of liquid CO2 drops in water under a Taylor flow regime is
studied using a straight microchannel (length/width ~ 100). A general form of a
mathematical model of the solvent-side mass transfer coefficient (ks) is
developed first. Based on formulations of the surface area (A) and the volume (V)
of a general Taylor drop in a rectangular microchannel, a specific form of ks is
derived. Drop length and speed are experimentally measured at three specified
positions of the straight channel, namely, immediately after drop generation
(position 1), the midpoint of the channel (position 2) and the end of the channel
(position 3). The reductions of drop length (Lx, x = 1, 2, 3) from position 1 to
2 and down to 3 are used to quantify the drop shrinkage. Using the specific
model, ks is calculated mainly based on Lx and drop flowing time (t). Results
show that smaller CO2 drops produced by lower flow rate ratios (QLCO2/QH2O) are
generally characterized by higher (nearly three times) ks and Sherwood numbers
than those produced by higher QLCO2/QH2O, which is essentially attributed to the
larger effective portion of the smaller drop contributing in the mass transfer
under same levels of the flowing time and the surface-to-volume ratio (~ 104 m-1)
of all drops. Based on calculated pressure drops of the segmented flow in
microchannel, the Peng-Robinson equation of state (EOS) and initial pressures of
drops at the T-junction in experiments, overall pressure drop (DeltaPt) in the
straight channel as well as the resulted drop volume change are quantified.
DeltaPt from position 1 to 3 is by average 3.175 kPa with a ~1.6% standard error,
which only leads to relative drop volume changes of 0.30/00 to 0.520/00.
PMID- 29337301
TI - Hepatic Gi signaling regulates whole-body glucose homeostasis.
AB - An increase in hepatic glucose production (HGP) is a key feature of type 2
diabetes. Excessive signaling through hepatic Gs-linked glucagon receptors
critically contributes to pathologically elevated HGP. Here, we tested the
hypothesis that this metabolic impairment can be counteracted by enhancing
hepatic Gi signaling. Specifically, we used a chemogenetic approach to
selectively activate Gi-type G proteins in mouse hepatocytes in vivo.
Unexpectedly, activation of hepatic Gi signaling triggered a pronounced increase
in HGP and severely impaired glucose homeostasis. Moreover, increased Gi
signaling stimulated glucose release in human hepatocytes. A lack of functional
Gi-type G proteins in hepatocytes reduced blood glucose levels and protected mice
against the metabolic deficits caused by the consumption of a high-fat diet.
Additionally, we delineated a signaling cascade that links hepatic Gi signaling
to ROS production, JNK activation, and a subsequent increase in HGP. Taken
together, our data support the concept that drugs able to block hepatic Gi
coupled GPCRs may prove beneficial as antidiabetic drugs.
PMID- 29337302
TI - Critical roles of alphaII spectrin in brain development and epileptic
encephalopathy.
AB - The nonerythrocytic alpha-spectrin-1 (SPTAN1) gene encodes the cytoskeletal
protein alphaII spectrin. Mutations in SPTAN1 cause early infantile epileptic
encephalopathy type 5 (EIEE5); however, the role of alphaII spectrin in
neurodevelopment and EIEE5 pathogenesis is unknown. Prior work suggests that
alphaII spectrin is absent in the axon initial segment (AIS) and contributes to a
diffusion barrier in the distal axon. Here, we have shown that alphaII spectrin
is expressed ubiquitously in rodent and human somatodendritic and axonal domains.
CRISPR-mediated deletion of Sptan1 in embryonic rat forebrain by in utero
electroporation caused altered dendritic and axonal development, loss of the AIS,
and decreased inhibitory innervation. Overexpression of human EIEE5 mutant SPTAN1
in embryonic rat forebrain and mouse hippocampal neurons led to similar
developmental defects that were also observed in EIEE5 patient-derived neurons.
Additionally, patient-derived neurons displayed aggregation of spectrin
complexes. Taken together, these findings implicate alphaII spectrin in critical
aspects of dendritic and axonal development and synaptogenesis, and support a
dominant-negative mechanism of SPTAN1 mutations in EIEE5.
PMID- 29337303
TI - PD-L1 on host cells is essential for PD-L1 blockade-mediated tumor regression.
AB - Programmed death-ligand 1 (PD-L1) expression on tumor cells is essential for T
cell impairment, and PD-L1 blockade therapy has shown unprecedented durable
responses in several clinical studies. Although higher expression of PD-L1 on
tumor cells is associated with a better immune response after Ab blockade, some
PD-L1-negative patients also respond to this therapy. In the current study, we
explored whether PD-L1 on tumor or host cells was essential for anti-PD-L1
mediated therapy in 2 different murine tumor models. Using real-time imaging in
whole tumor tissues, we found that anti-PD-L1 Ab accumulates in tumor tissues,
regardless of the status of PD-L1 expression on tumor cells. We further observed
that, while PD-L1 on tumor cells was largely dispensable for the response to
checkpoint blockade, PD-L1 in host myeloid cells was essential for this response.
Additionally, PD-L1 signaling in defined antigen-presenting cells (APCs)
negatively regulated and inhibited T cell activation. PD-L1 blockade inside
tumors was not sufficient to mediate regression, as limiting T cell trafficking
reduced the efficacy of the blockade. Together, these findings demonstrate that
PD-L1 expressed in APCs, rather than on tumor cells, plays an essential role in
checkpoint blockade therapy, providing an insight into the mechanisms of this
therapy.
PMID- 29337304
TI - The host protecting the tumor from the host - targeting PD-L1 expressed by host
cells.
AB - Tumors frequently escape from immune surveillance by hijacking the natural
control mechanisms that regulate normal immune responses. The programmed death-1
receptor (PD-1) on T cells normally helps limit excessive immune activation, but
it can also suppress beneficial antitumor immunity. In the clinic, blocking
either PD-1 or one of its principal counterligands, programmed death-ligand 1 (PD
L1), can lead to dramatic responses in certain patients. Because PD-L1 can be
expressed by both the tumor cells themselves and also the host cells, including
host immune cells, the actual mechanistic target of therapy has remained unclear.
In the current issue of the JCI, two papers, one by Tang and colleagues and the
other by Lin and colleagues, used a variety of mouse tumor models to demonstrate
that the relevant target for therapy in each case was the PD-L1 molecules
expressed by host cells and not by tumor cells. If this finding is generalized to
humans, then it would suggest that the tumor persuades the host to actively
suppress its own attempted immune response against the tumor cells.
PMID- 29337305
TI - Host expression of PD-L1 determines efficacy of PD-L1 pathway blockade-mediated
tumor regression.
AB - Programmed death-1 receptor (PD-L1, B7-H1) and programmed cell death protein 1
(PD-1) pathway blockade is a promising therapy for treating cancer. However, the
mechanistic contribution of host and tumor PD-L1 and PD-1 signaling to the
therapeutic efficacy of PD-L1 and PD-1 blockade remains elusive. Here, we
evaluated 3 tumor-bearing mouse models that differ in their sensitivity to PD-L1
blockade and demonstrated a loss of therapeutic efficacy of PD-L1 blockade in
immunodeficient mice and in PD-L1- and PD-1-deficient mice. In contrast, neither
knockout nor overexpression of PD-L1 in tumor cells had an effect on PD-L1
blockade efficacy. Human and murine studies showed high levels of functional PD
L1 expression in dendritic cells and macrophages in the tumor microenvironments
and draining lymph nodes. Additionally, expression of PD-L1 on dendritic cells
and macrophages in ovarian cancer and melanoma patients correlated with the
efficacy of treatment with either anti-PD-1 alone or in combination with anti
CTLA-4. Thus, PD-L1-expressing dendritic cells and macrophages may
mechanistically shape and therapeutically predict clinical efficacy of PD-L1/PD-1
blockade.
PMID- 29337306
TI - Zinc transporter Slc39a8 is essential for cardiac ventricular compaction.
AB - Isolated left ventricular noncompaction (LVNC) results from excessive
trabeculation and impaired myocardial compaction during heart development. The
extracellular matrix (ECM) that separates endocardium from myocardium plays a
critical but poorly understood role in ventricular trabeculation and compaction.
In an attempt to characterize solute carrier family 39 member 8-null (Slc39a8
null) mice, we discovered that homozygous null embryos do not survive
embryogenesis and exhibit a cardiac phenotype similar to human LVNC. Slc39a8
encodes a divalent metal cation importer that has been implicated in ECM
degradation through the zinc/metal regulatory transcription factor 1 (Zn/MTF1)
axis, which promotes the expression of ECM-degrading enzymes, including Adamts
metalloproteinases. Here, we have shown that Slc39a8 is expressed by endothelial
cells in the developing mouse heart, where it serves to maintain cellular Zn
levels. Furthermore, Slc39a8-null hearts exhibited marked ECM accumulation and
reduction of several Adamts metalloproteinases. Consistent with the in vivo
observations, knockdown of SLC39A8 in HUVECs decreased ADAMTS1 transcription by
decreasing cellular Zn uptake and, as a result, MTF1 transcriptional activity.
Our study thus identifies a gene underlying ventricular trabeculation and
compaction development, and a pathway regulating ECM during myocardial
morphogenesis.
PMID- 29337307
TI - A double negative: inhibition of hepatic Gi signaling improves glucose
homeostasis.
AB - Hepatic glucose production (HGP) is a key determinant of glucose homeostasis.
Glucagon binding to its cognate seven-transmembrane Gs-coupled receptor in
hepatocytes stimulates cAMP production, resulting in increased HGP. In this issue
of the JCI, Rossi and colleagues tested the hypothesis that activation of hepatic
Gi-coupled receptors, which should inhibit cAMP production, would oppose the cAMP
inducing action of glucagon and thereby decrease HGP. Surprisingly, however, the
opposite occurred: activation of Gi signaling increased HGP via a novel
mechanism, while inhibition of Gi signaling reduced HGP. These results define a
new physiologic role for hepatic Gi signaling and identify a potential
therapeutic target for HGP regulation.
PMID- 29337308
TI - RAGE binds preamyloid IAPP intermediates and mediates pancreatic beta cell
proteotoxicity.
AB - Islet amyloidosis is characterized by the aberrant accumulation of islet amyloid
polypeptide (IAPP) in pancreatic islets, resulting in beta cell toxicity, which
exacerbates type 2 diabetes and islet transplant failure. It is not fully clear
how IAPP induces cellular stress or how IAPP-induced toxicity can be prevented or
treated. We recently defined the properties of toxic IAPP species. Here, we have
identified a receptor-mediated mechanism of islet amyloidosis-induced
proteotoxicity. In human diabetic pancreas and in cellular and mouse models of
islet amyloidosis, increased expression of the receptor for advanced glycation
endproducts (RAGE) correlated with human IAPP-induced (h-IAPP-induced) beta cell
and islet inflammation, toxicity, and apoptosis. RAGE selectively bound toxic
intermediates, but not nontoxic forms of h-IAPP, including amyloid fibrils. The
isolated extracellular ligand-binding domains of soluble RAGE (sRAGE) blocked
both h-IAPP toxicity and amyloid formation. Inhibition of the interaction between
h-IAPP and RAGE by sRAGE, RAGE-blocking antibodies, or genetic RAGE deletion
protected pancreatic islets, beta cells, and smooth muscle cells from h-IAPP
induced inflammation and metabolic dysfunction. sRAGE-treated h-IAPP Tg mice were
protected from amyloid deposition, loss of beta cell area, beta cell
inflammation, stress, apoptosis, and glucose intolerance. These findings
establish RAGE as a mediator of IAPP-induced toxicity and suggest that targeting
the IAPP/RAGE axis is a potential strategy to mitigate this source of beta cell
dysfunction in metabolic disease.
PMID- 29337309
TI - Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons.
AB - Parkinson's disease is characterized by the loss of dopamine (DA) neurons in the
substantia nigra pars compacta (SNc). DA neurons in the ventral tegmental area
are more resistant to this degeneration than those in the SNc, though the
mechanisms for selective resistance or vulnerability remain poorly understood. A
key to elucidating these processes may lie within the subset of DA neurons that
corelease glutamate and express the vesicular glutamate transporter VGLUT2. Here,
we addressed the potential relationship between VGLUT expression and DA neuronal
vulnerability by overexpressing VGLUT in DA neurons of flies and mice. In
Drosophila, VGLUT overexpression led to loss of select DA neuron populations.
Similarly, expression of VGLUT2 specifically in murine SNc DA neurons led to
neuronal loss and Parkinsonian behaviors. Other neuronal cell types showed no
such sensitivity, suggesting that DA neurons are distinctively vulnerable to
VGLUT2 expression. Additionally, most DA neurons expressed VGLUT2 during
development, and coexpression of VGLUT2 with DA markers increased following
injury in the adult. Finally, conditional deletion of VGLUT2 made DA neurons more
susceptible to Parkinsonian neurotoxins. These data suggest that the balance of
VGLUT2 expression is a crucial determinant of DA neuron survival. Ultimately,
manipulation of this VGLUT2-dependent process may represent an avenue for
therapeutic development.
PMID- 29337310
TI - OATP1B2 deficiency protects against paclitaxel-induced neurotoxicity.
AB - Paclitaxel is among the most widely used anticancer drugs and is known to cause a
dose-limiting peripheral neurotoxicity, the initiating mechanisms of which remain
unknown. Here, we identified the murine solute carrier organic anion-transporting
polypeptide B2 (OATP1B2) as a mediator of paclitaxel-induced neurotoxicity.
Additionally, using established tests to assess acute and chronic paclitaxel
induced neurotoxicity, we found that genetic or pharmacologic knockout of OATP1B2
protected mice from mechanically induced allodynia, thermal hyperalgesia, and
changes in digital maximal action potential amplitudes. The function of this
transport system was inhibited by the tyrosine kinase inhibitor nilotinib through
a noncompetitive mechanism, without compromising the anticancer properties of
paclitaxel. Collectively, our findings reveal a pathway that explains the
fundamental basis of paclitaxel-induced neurotoxicity, with potential
implications for its therapeutic management.
PMID- 29337312
TI - China CO2 emission accounts 1997-2015.
AB - China is the world's top energy consumer and CO2 emitter, accounting for 30% of
global emissions. Compiling an accurate accounting of China's CO2 emissions is
the first step in implementing reduction policies. However, no annual, officially
published emissions data exist for China. The current emissions estimated by
academic institutes and scholars exhibit great discrepancies. The gap between the
different emissions estimates is approximately equal to the total emissions of
the Russian Federation (the 4th highest emitter globally) in 2011. In this study,
we constructed the time-series of CO2 emission inventories for China and its 30
provinces. We followed the Intergovernmental Panel on Climate Change (IPCC)
emissions accounting method with a territorial administrative scope. The
inventories include energy-related emissions (17 fossil fuels in 47 sectors) and
process-related emissions (cement production). The first version of our dataset
presents emission inventories from 1997 to 2015. We will update the dataset
annually. The uniformly formatted emission inventories provide data support for
further emission-related research as well as emissions reduction policy-making in
China.
PMID- 29337311
TI - Dinaciclib induces immunogenic cell death and enhances anti-PD1-mediated tumor
suppression.
AB - Blockade of the checkpoint inhibitor programmed death 1 (PD1) has demonstrated
remarkable success in the clinic for the treatment of cancer; however, a majority
of tumors are resistant to anti-PD1 monotherapy. Numerous ongoing clinical
combination therapy studies will likely reveal additional therapeutics that
complement anti-PD1 blockade. Recent studies found that immunogenic cell death
(ICD) improves T cell responses against different tumors, thus indicating that
ICD may further augment antitumor immunity elicited by anti-PD1. Here, we
observed antitumor activity following combinatorial therapy with anti-PD1 Ab and
the cyclin-dependent kinase inhibitor dinaciclib in immunocompetent mouse tumor
models. Dinaciclib induced a type I IFN gene signature within the tumor, leading
us to hypothesize that dinaciclib potentiates the effects of anti-PD1 by
eliciting ICD. Indeed, tumor cells treated with dinaciclib showed the hallmarks
of ICD including surface calreticulin expression and release of high mobility
group box 1 (HMGB1) and ATP. Mice treated with both anti-PD1 and dinaciclib
showed increased T cell infiltration and DC activation within the tumor,
indicating that this combination improves the overall quality of the immune
response generated. These findings identify a potential mechanism for the
observed benefit of combining dinaciclib and anti-PD1, in which dinaciclib
induces ICD, thereby converting the tumor cell into an endogenous vaccine and
boosting the effects of anti-PD1.
PMID- 29337313
TI - Complete genome sequencing of the luminescent bacterium, Vibrio qinghaiensis sp.
Q67 using PacBio technology.
AB - Vibrio qinghaiensis sp.-Q67 (Vqin-Q67) is a freshwater luminescent bacterium that
continuously emits blue-green light (485 nm). The bacterium has been widely used
for detecting toxic contaminants. Here, we report the complete genome sequence of
Vqin-Q67, obtained using third-generation PacBio sequencing technology.
Continuous long reads were attained from three PacBio sequencing runs and reads
>500 bp with a quality value of >0.75 were merged together into a single dataset.
This resultant highly-contiguous de novo assembly has no genome gaps, and
comprises two chromosomes with substantial genetic information, including protein
coding genes, non-coding RNA, transposon and gene islands. Our dataset can be
useful as a comparative genome for evolution and speciation studies, as well as
for the analysis of protein-coding gene families, the pathogenicity of different
Vibrio species in fish, the evolution of non-coding RNA and transposon, and the
regulation of gene expression in relation to the bioluminescence of Vqin-Q67.
PMID- 29337315
TI - Correction: One-step coelectrodeposition-assisted layer-by-layer assembly of gold
nanoparticles and reduced graphene oxide and its self-healing three-dimensional
nanohybrid for an ultrasensitive DNA sensor.
AB - Correction for 'One-step coelectrodeposition-assisted layer-by-layer assembly of
gold nanoparticles and reduced graphene oxide and its self-healing three
dimensional nanohybrid for an ultrasensitive DNA sensor' by Jayakumar Kumarasamy,
et al., Nanoscale, 2018, DOI: 10.1039/c7nr06952a.
PMID- 29337314
TI - The reconstruction of 2,631 draft metagenome-assembled genomes from the global
oceans.
AB - Microorganisms play a crucial role in mediating global biogeochemical cycles in
the marine environment. By reconstructing the genomes of environmental organisms
through metagenomics, researchers are able to study the metabolic potential of
Bacteria and Archaea that are resistant to isolation in the laboratory. Utilizing
the large metagenomic dataset generated from 234 samples collected during the
Tara Oceans circumnavigation expedition, we were able to assemble 102 billion
paired-end reads into 562 million contigs, which in turn were co-assembled and
consolidated in to 7.2 million contigs >=2 kb in length. Approximately 1 million
of these contigs were binned to reconstruct draft genomes. In total, 2,631 draft
genomes with an estimated completion of >=50% were generated (1,491 draft genomes
>70% complete; 603 genomes >90% complete). A majority of the draft genomes were
manually assigned phylogeny based on sets of concatenated phylogenetic marker
genes and/or 16S rRNA gene sequences. The draft genomes are now publically
available for the research community at-large.
PMID- 29337316
TI - Enhanced selectivity for Mg2+ with a phosphinate-based chelate: APDAP versus
APTRA.
AB - o-Aminophenol-N,N,O-triacetate, known as APTRA, is one of the most well
established ligands for targeting magnesium ions but, like other aminocarboxylate
ligands, it binds Ca2+ much more strongly than Mg2+. The synthesis of an O
phosphinate analogue of APTRA is reported here, namely o-aminophenol-N,N
diacetate-O-methylene-methylphosphinate, referred to as APDAP. Metal binding
studies monitored using UV-visible spectroscopy show that the affinity of APDAP
for Ca2+ is reduced by over two orders of magnitude compared to APTRA, and for
Zn2+ by over three orders of magnitude, whereas the affinity for Mg2+ is
attenuated to a much lesser extent, by a factor of only about 7. The selectivity
towards Mg2+ is thus substantially improved. DFT calculations support the notion
that longer P-O and P-C bonds in APDAP (compared to corresponding C-O and C-C
bonds in APTRA) favour a larger angle at the metal, an effect that is less
unfavourable for smaller ions like Mg2+ than for larger ions such as Ca2+.
Derivatives of APDAP can be anticipated that will offer improved sensing of Mg2+
in the presence of Ca2+, in the physiologically important millimolar
concentration range.
PMID- 29337317
TI - Correction: Nucleobases, nucleosides, and nucleotides: versatile biomolecules for
generating functional nanomaterials.
AB - Correction for 'Nucleobases, nucleosides, and nucleotides: versatile biomolecules
for generating functional nanomaterials' by Fang Pu et al., Chem. Soc. Rev.,
2018, DOI: .
PMID- 29337318
TI - HOMEs for plants and microbes - a phenotyping approach with quantitative control
of signaling between organisms and their individual environments.
AB - We describe a simple, scalable, modular, and frugal approach to create model
ecosystems as millifluidic networks of interconnected habitats (hosting microbes
or plants), which offers (i) quantitative and dynamic control over the exchange
of chemicals between habitats, and (ii) independent control over their
environment. Oscillatory laminar flows produce regions of vortex mixing around
obstacles. When these overlap, rapid mass transport by dispersion occurs, which
is quantitatively describable as diffusion, but is directional and tunable in
rate over 3 orders of magnitude. This acceleration in the rate of diffusion is
equivalent to reducing the distance between the habitats, and therefore, the
organisms, down to the length scales characteristic of signaling in soil (<2 mm).
PMID- 29337319
TI - The effects of interaction between particulate matter and temperature on
mortality in Beijing, China.
AB - BACKGROUND: the effects of interaction between temperature and inhalable
particulate matter (aerodynamic diameter < 10 MUm, PM10) on mortality have been
examined in some previous studies, but the results were inconsistent. This study
aims to explore whether the effects of PM10 on daily non-accidental,
cardiovascular and respiratory mortality were modified by temperature levels in
Beijing from 2006 to 2009. METHODS: we applied a bivariate response surface model
and temperature-stratified model based on time-series Poisson generalized
additive models (GAMs) to examine the interactive effects in single- and two
pollutant models. The modification of age and gender was examined in subgroup
analyses. RESULTS: the median of temperature (15.9 degrees C) and visualized
turning point (20 degrees C) were chosen as cut-offs to define the temperature
strata as two levels (low and high). Results showed that the effect estimates of
PM10 were stronger at the high temperature level for non-accidental,
cardiovascular and respiratory mortality than at the low temperature level. When
controlling the moving average lag of temperature for 14 days, the effect
estimates per 10 MUg m-3 increase in PM10 for non-accidental, cardiovascular and
respiratory mortality increased 0.14% (95% CI: 0.05, 0.22), 0.12% (95% CI: 0.02,
0.23) and 0.14% (95% CI: -0.06, 0.34) when the temperature was low and 0.24% (95%
CI: 0.12, 0.35), 0.17% (95% CI: 0.01, 0.34) and 0.45% (95% CI: 0.13, 0.78) at the
high temperature level, respectively. In the two-pollutant model, the effects of
PM10 were attenuated at both high and low temperatures at all lags after
adjusting SO2 and NO2. The PM10 effects were stronger at the high temperature
level for females and elderly people (>=65 years old). CONCLUSION: the findings
suggest that daily mortality attributed to PM10 might be modified by temperature.
The interaction between air pollution and global climate change has potential
strategy and policy implications.
PMID- 29337320
TI - Homochiral hexanuclear nickel(ii) metallocyclic structures with high activity for
the photocatalytic degradation of organic dyes.
AB - Enantiopure ligands, namely (R,R)- and (S,S)-2,2'-(1,4-phenylene) bis(4,5
dihydrothiazole-4-carboxylic acid) (H2LRR, and H2LSS) were synthesized, and
homochiral metallocyclic rings {Ni6LRR6(H2O)12} (1RR) and {Ni6LSS6(H2O)12} (1SS)
were obtained and their structures were determined. The complexes exhibit
excellent activity for the photocatalytic degradation of organic dyes.
PMID- 29337322
TI - Structural revision of two unusual rhamnofolane diterpenes, curcusones I and J,
by means of DFT calculations of NMR shifts and coupling constants.
AB - The stereochemical revision of two recently reported rhamnofolane diterpenes,
curcusones I and J, was enabled by quantum calculations of NMR shifts and
coupling constants at DFT levels. DP4+ results and reexamination of the NMR data
suggest that curcusones I and J should be revised as CS32 and CS28, respectively.
PMID- 29337321
TI - Synthesis, spectroscopic investigation, and DFT study of N,N'-disubstituted
ferrocene-based thiourea complexes as potent anticancer agents.
AB - In the present work, the synthesis, characterization (FT-IR, multinuclear (1H and
13C) NMR, AAS, Raman, and elemental analyses), DNA binding (cyclic voltammetry,
UV-Vis spectroscopy), and in vitro biological screening of nine new ferrocene
incorporated thioureas (A1-A9) are reported. Furthermore, the single-crystal X
ray structure of compound A8 was also determined. The ferrocene-based N,N'
disubstituted thioureas were derived by allowing the ferrocenyl anilines to react
with freshly prepared isothiocyanates under a N2 atmosphere in dry acetone. The
DNA binding studies performed by cyclic voltammetry and UV-Vis spectroscopy
produced results that are in close agreement with one another for the binding
constants (K) and an electrostatic mode of interaction was observed. The
DFT/B3LYP method was used to determine the charge distribution and HOMO/LUMO
energies of the optimized structure. The DFT calculated HOMO and LUMO energies
correlate well with the experimentally determined redox potential values. The
synthesized ferrocenyl thioureas exhibited good scavenging activity against the
1,1-diphenyl-2-picrylhydrazyl radical (DPPH). These complexes were also scanned
for their in vitro cytotoxic activity against MCF-7 carcinoma cells, and also
towards the non-cancerous cell line MCF-10A. The results showed modest
cytotoxicity against the subjected cancer cell line compared with a standard
chemotherapeutic drug (cisplatin). However, these ferrocenyl derivatives have
fewer toxic effects in normal cells.
PMID- 29337323
TI - Conversion of CO2 into cyclic carbonates by a Co(ii) metal-organic framework and
the improvement of catalytic activity via nanocrystallization.
AB - The Co(ii) metal-organic framework (MOF) {[Co(MU3-L)(H2O)].0.5H2O}n (1, H2L =
thiazolidine 2,4-dicarboxylic acid) with rich Lewis acid sites was used as a
catalyst for the conversion of CO2 and propylene oxide into propylene carbonate
with a yield of up to 98% under 50 degrees C and 1 atm. 1 exhibited excellent
reusability, which could be regenerated easily for at least five runs without a
decrease in the yield. Importantly, we synthesized two types of nano-crystals (N1
and N2) of 1 with polyvinylpyrrolidone (PVP) and hexadecyltrimethylammonium
bromide (CTAB) as surfactants, respectively, and investigated their catalytic
properties in comparison with that of 1 in the powder phase. A significant
enhancement in both catalytic efficiency and product yield was observed when 1
was nano-crystallized. This is the first investigation about the relationship
between the morphology and the catalytic parameters of MOFs. The results showed a
strategy for efficiently applying MOFs as catalysts towards CO2 conversion, which
could also be used in other MOF-catalyzed processes.
PMID- 29337324
TI - Polymerization kinetics of a multi-functional silica precursor studied using a
novel Monte Carlo simulation technique.
AB - Silica polymerization has been extensively used to synthesize various fascinating
materials for industrial and technological applications. The polymerization
protocol is modified by altering several parameters (such as the concentration of
the precursor, temperature, pH) heuristically to obtain the desired end product.
To properly understand the effect of such parameters, knowledge of molecular
events occurring during the process of polymerization is essential. In this work,
we developed algorithms to capture molecular events such as translation,
rotation, and reactions using the reaction ensemble Monte Carlo (REMC) technique.
Our algorithms simulate molecular events in accordance with physical time by
correctly scaling the movements of a cluster with the monomer, thereby capturing
the kinetics of the process. We studied the polymerization of the four
coordinated silica (f4) precursor using our algorithm and observed excellent
agreement between simulation results and experimental data. The algorithm was
also used to study the polymerization of the three coordinated silica (f3)
precursor and it was found that our simulations capture experimental kinetics
well, thereby confirming that the developed algorithms are robust. We studied the
effect of the functionality of the precursor on polymerization kinetics and the
resulting structure by simulating silica systems having a mixture of two, three
and four functional (f2, f3, and f4) silica precursors. We observed that network
formation and cluster size decrease with the increase in the concentration of the
f2 precursor. The radius of gyration (Rg) of the system initially increases due
to network formation and decreases later due to the collapse of a large cluster.
The Rg is directly correlated with the total number of primitive rings present in
the system. The molecular level understanding obtained will be useful in the
design of tailored silica nanoparticles.
PMID- 29337325
TI - Design of donor-acceptor copolymers for organic photovoltaic materials: a
computational study.
AB - 80 different push-pull type organic chromophores which possess Donor-Acceptor (D
A) and Donor-Thiophene-Acceptor-Thiophene (D-T-A-T) structures have been
systematically investigated by means of density functional theory (DFT) and time
dependent DFT (TD-DFT) at the B3LYP/6-311G* level. The introduction of thiophene
(T) in the chain has allowed us to monitor the effect of pi-spacers. Benchmark
studies on the methodology have been carried out to predict the HOMO and LUMO
energies and optical band gaps of the D-A systems accurately. The HOMO and LUMO
energies and transition dipoles are seen to converge for tetrameric oligomers,
and the latter have been used as optimal chain length to evaluate various
geometrical and optoelectronic properties such as bond length alternations,
distortion energies, frontier molecular orbital energies, reorganization energies
and excited-state vertical transition of the oligomers. Careful analysis of our
findings has allowed us to propose potential donor-acceptor couples to be used in
organic photovoltaic cells.
PMID- 29337326
TI - Synthesis, characterization and derivatization of hydroxyl-functionalized
iron(ii) bis(NHC) complexes.
AB - The syntheses of a novel hydroxyl-functionalized tetradentate NHC/pyridine hybrid
ligand and the corresponding Ag(i) and Fe(ii) complexes are presented.
Spectroscopic and X-ray diffraction techniques are used for structural
investigations and cyclic voltammetry measurements reveal interesting electronic
properties. Transmetalation of the trinuclear Ag(i) complex (C1) yields a
mononuclear and a dinuclear iron(ii) bis(NHC) complex (C2 and C3), which can be
separated by stepwise precipitation. The former is isostructural to iron(ii)
bis(NHC) complex A, which is a versatile oxidation catalyst. Furthermore,
suitable conditions for esterification reactions of the ligand precursor and
iron(ii) bis(NHC) complex (C2) have been established, demonstrating the utility
of the hydroxyl functionality for immobilization and derivatization purposes.
PMID- 29337327
TI - Modulating inflammation in a cutaneous chronic wound model by IL-10 released from
collagen-silica nanocomposites via gene delivery.
AB - Cutaneous chronic wounds remain a major clinical challenge which requires the
development of novel wound dressings. Previously, we showed that collagen-silica
nanocomposites consisting of polyethyleneimine (PEI)-DNA complexes associated
with silica nanoparticles (SiNP), collagen hydrogel and 3T3 fibroblasts, can work
as a local "cell factory". Indeed, the "in-gel" transfection leads to a sustained
production and release of biomolecules. Herein, we further explored the
possibility for nanocomposites to deliver interleukin-10 (IL-10), a potent anti
inflammatory cytokine, which favors tissue repair. Its anti-inflammatory effect
was evaluated in an in vitro inflammation model carried out by LPS
(lipopolysaccharide) activation of macrophages embedded in collagen gel. The IL
10 synthesis from nanocomposites was detected over one week in the range of 200
400 pg mL-1 and reached a maximum at day 5 without any observed cytotoxic
effects. PEI10-SiNP outperformed free PEI10 and PEI25-SiNP, implying that the
introduction of SiNP improved the transfection efficiency of low Mw of PEI. In
addition, the structure and mechanical properties of collagen-silica
nanocomposites were stable over one week. Subsequently, the ability of
nanocomposites to modulate inflammation was tested in a 3D model of inflammation.
The decrease of TNF-alpha and IL-1beta gene expression by 20-80% indicated
successful inhibition of inflammation by IL-10 released from nanocomposites.
Taken together, the nanocomposites are capable of producing effective doses of IL
10 which inhibit the synthesis of pro-inflammatory cytokines and favor the
expression of wound healing cytokines. Therefore, the as-constructed 3D gene
delivery system represents a promising strategy for the controlled release of
therapeutic biomolecules favoring cutaneous wound healing.
PMID- 29337328
TI - Self-assembly of high-index faceted gold nanocrystals to fabricate tunable
coupled plasmonic superlattices.
AB - Herein, we present an effective bottom-up strategy to fabricate unprecedented
macroscopic two-dimensional (2D) plasmonic gold superlattices composed of high
index faceted gold nanocrystal building blocks (NBBs) at the air-liquid
interface. In this approach, a synergistic electrostatic and layered self
assembly technique was executed using unique icosidodecahedral gold nanocrystals.
It showed that centimeter-squared areas of close-packed monolayer films were
formed, and the interparticle spacing of neighbouring Au NBBs could be facilely
manipulated from hundreds to several nanometers. Optical characterization
demonstrated that particular plasmonic coupling could occur and enhance in a wide
spectral range (visible and near-IR) as the self-assembled Au superlattices were
tuned for an appropriate gap distance and specific NBB size; however, the
orientation of individual NBBs remained somewhat unorganized. Thus, the well
pronounced shift of localized surface plasmon resonances (LSPR) and the in-depth
resonance splitting behaviors were presented in our investigations. Furthermore,
corresponding electromagnetic simulations showed good agreement with the
experimental results; this indicated that a new class of tunable coupled
plasmonic Au superlattices was realized. This study complements the insights into
the plasmonic coupling of layered Au superlattices and enables the colloidal self
assembly to extend to unconventional NBBs; thus, it may facilitate the design of
novel plasmonic metamaterials or other superstructures for desired
functionalities and applications in the future.
PMID- 29337330
TI - ?
PMID- 29337329
TI - Ultra-low-temperature growth of CdS quantum dots on g-C3N4 nanosheets and their
photocatalytic performance.
AB - CdS quantum dots deposited on carbon nitride (g-C3N4) nanosheets have been
synthesized by ultra-low temperature (-60 degrees C) liquid phase precipitation
reactions. The obtained CdS quantum dots were uniformly distributed on the
surface of the g-C3N4 nanosheets with an average diameter of 5 nm.
Correspondingly, CdS/g-C3N4 exhibits a highly enhanced photocatalytic
performance.
PMID- 29337331
TI - ?
PMID- 29337333
TI - ?
PMID- 29337332
TI - ?
PMID- 29337334
TI - ?
PMID- 29337335
TI - ?
PMID- 29337336
TI - ?
PMID- 29337337
TI - ?
AB - Automatic infectious disease consultant alert is associated with decreased
mortality and readmission rate in Staphylococcus aureus bacteriemia A management
plan was implemented at a 2000 bed teaching hospital where positive blood
cultures with growth of Staphylococcus aureus were reported simultaneously to the
ordering unit and to the Infectious Disease Consultant. Readmission rate and 30
day mortality were compared one year before and one year after introduction of
the management plan. Out of totally 320 respectively 321 patients with SAB 252
and 244 were included in the study. 30-day mortality decreased from 26/252 (10%)
to 14/244 (5,7%) (p=0.059) when all patients with SAB were included and to 9/193
(4,7%) (p=0,026) when only patients who received a formal consultation after
introduction of the management plan were included. The rate of readmission within
30 days declined from 38/227 (17%) in 2014-2015 to 24/230 (10%) in 2015-2016
(p=0,049).
PMID- 29337338
TI - ?
AB - Good outcomes when emergency physicians diagnosed deep vein thrombosis Deep vein
thrombosis of the lower limb is best diagnosed with ultrasound. Internationally,
several studies have shown promising and often equal results when emergency
physicians have been compared with radiologists in diagnosing thrombosis. Our
results confirm these findings in a non-academic hospital and for the first time
in a Swedish setting. Our findings form the basis for a multi-centre study on new
diagnostic routines in patients with suspected proximal deep vein thrombosis in
the emergency department, potentially resulting in faster and more resource
effective management.
PMID- 29337339
TI - ?
AB - Risk of optic nerve injury after prolonged Trendelenburg's position Postoperative
loss of vision due to acute ischaemic optic nerve injury is a rare complication
following pelvic surgery. A steep Trendelenburg's position of the patient, high
intraabdominal pressure and a long operative time in Trendelenburg's position are
recognised risk factors associated with robot-assisted pelvic surgery. This
manuscript presents the underlying pathophysiologic mechanism. Practical tips and
tricks for prevention are discussed.
PMID- 29337340
TI - ?
PMID- 29337341
TI - ?
AB - MMR vaccination in 6-9 month olds Vaccination against measles using the MMR
vaccine is licensed from 9 months of age, but is used off-label from 6 months of
age during or when travelling to areas with an ongoing measles outbreak. In this
review of the published literature, studies on MMR vaccination in this age group
are limited and small in size. Immunogenicity studies indicate that infants under
9 months respond with lower antibody titres but comparable T cell responses
against measles. The safety profile of the vaccine does not appear to differ
between infants vaccinated earlier or later. Vaccination from 6 months of age
should be recommended if the risk of being infected with measles is considered
greater than the risk of not attaining full vaccination protection.
PMID- 29337342
TI - Polysaccharides Reduce Absorption and Mutagenicity of 3-Amino-1,4-Dimethyl-5H
Pyrido[4,3-b]Indole In Vitro and In Vivo.
AB - : 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) is a group 2B carcinogen
characterized by the International Agency for Research on Cancer (IARC) and great
efforts have been taken to reduce Trp-P-1 mutagenicity to humans. In this study,
the effect of a reduction of Trp-P-1 on intestinal absorption as a promising
strategy was investigated. The data showed that when 20 mM Trp-P-1 cotransported
with 10 mM of sodium carboxymethyl cellulose (CMC), xanthan gum, or carrageenan,
the absorption rate of Trp-P-1 was reduced by 31.5%, 49.5%, or 72.9% in MDCK-MDR1
cell monolayer, respectively; and 64.6%, 83.4%, or 64.1% in rat intestinal
tissues, correspondingly. These 3 polysaccharides also reduced pharmacokinetic
parameters, that is, Cmax , AUC0-t , and AUC0-infinity , after Trp-P-1 was given
to rats intragastrically. However, gum arabic did not exhibit similar effects on
Trp-P-1 absorption in vitro or in vivo. The Ames test showed that these 3
polysaccharides reduced Trp-P-1 mutagenicity to Salmonella typhimurium TA98, but
gum arabic did not. Isothermal titration calorimetry assay indicated that Trp-P-1
interacted with these 3 polysaccharides. Thermodynamic study showed that the
actual value of ?H <0, but its absolute value greater than the corresponding
value of T?S, suggest a specific interaction between Trp-P-1 and these 3
polysaccharides, probably through the hydrogen bond and/or ion interaction.
Reduction of Trp-P-1 intestinal absorption using food additives could be one of
the strategies to suppress Trp-P-1-induced carcinogenesis in human. PRACTICAL
APPLICATION: 1.This study provides insightful information for the food industry
how gum arabic, xanthan gum, kappa carrageenan, and sodium carboxymethyl
cellulose affect the absorption of Trp-P-1. 2.This study also provides novel
information regarding a better formulation for meat products to reduce Trp-P-1
absorption.
PMID- 29337343
TI - Antimicrobial-Resistance Genetic Markers in Potentially Pathogenic Gram Positive
Cocci Isolated from Brazilian Soft Cheese.
AB - Although most Brazilian dairy products meet high technological standards, there
are quality issues regarding milk production, which may reduce the final product
quality. Several microbial species may contaminate milk during manufacture and
handling. If antimicrobial usage remains uncontrolled in dairy cattle, the
horizontal transfer of antimicrobial resistance genes in foodstuffs may be of
particular concern for both food producers and dairy industry. This study focused
on the evaluation of putative Gram positive cocci in Minas cheese and of
antimicrobial and biocide resistance genes among the isolated bacteria.
Representative samples of 7 different industrially trademarked Minas cheeses (n =
35) were processed for selective culture and isolation of Gram positive cocci.
All isolated bacteria were identified by DNA sequencing of the 16S rRNA gene.
Antimicrobial resistance genes were screened by PCR. Overall, 208 strains were
isolated and identified as follows: Enterococcus faecalis (47.6%), Macrococcus
caseolyticus (18.3%), Enterococcus faecium (11.5%), Enterococcus caseliflavus
(7.7%), Staphylococcus haemolyticus (7.2%), Staphylococcus aureus (4.3%),
Staphylococcus epidermidis (2.9%), and Enterococcus hirae (0.5%). The genetic
markers mecA (78.0%) and smr (71.4%) were the most prevalent, but others were
also detected, such as blaZ (65.2%), msrA (60.9%), msrB (46.6%), linA (54.7%),
and aacA-aphD (47.6%). The occurrence of opportunist pathogenic bacteria
harboring antimicrobial resistance markers in the cheese samples are of special
concern, since these bacteria are not considered harmful contaminating agents
according to the Brazilian sanitary regulations. However, they are potentially
pathogenic bacteria and the cheese may be considered a reservoir for
antimicrobial resistance genes available for horizontal transfer through the food
chain, manufacturing personnel and consumers.
PMID- 29337344
TI - Microbiological Quality and Safety of Fresh Fruits and Vegetables at Retail
Levels in Korea.
AB - The aim of this study was to evaluate the microbiological quality and safety of
fresh produce at retail level in Korea in order to periodically update
information and establish available risks associated with consumption of fresh
fruits and vegetables. The samples from different markets located in 3 provinces
of South Korea were collected. The protocol in the Korean Food Standards Codex
was applied and generic Escherichia coli, coliforms, aerobic mesophilic bacteria
(AMB), and yeast and mold (YM) in 360 packaged and unpackaged fresh fruits and
vegetables were analyzed. Presence of pathogens was examined using real-time
polymerase chain reaction (q-PCR) after enrichment of samples. For all, the
microbial counts ranged from 1.7 to 10.6 log cfu/g for AMB, 2.2 to 7.9 log cfu/g
for coliforms, and 5.5 to 7.9 log cfu/g for YM. Three lettuce samples were
contaminated by E. coli with a bacterial load ranging from 2 to 4 log cfu/g.
Salmonella spp. were not detected in any fresh produce. Listeria monocytogenes,
E. coli O157:H7, and Staphylococcus aureus were found in 1 (0.6%), 3 (0.8%), and
5 (1.4%) fresh produce samples, respectively. Bacillus cereus (50.3%) and
Clostridium perfringens (13.3%) had the highest prevalence. These results
indicate the need for employing strict control measures and developing preventive
strategies to improve the quality and safety of fresh produce in Korea.
PMID- 29337345
TI - Sputum cytology during late-phase responses to inhalation challenge with
different allergens.
AB - BACKGROUND: In mouse models of allergic asthma, exposure to different allergens
can trigger distinct inflammatory subtypes in the airways. We investigated
whether this observation extends to humans. METHODS: We compared the frequency of
sputum inflammatory subtypes between mild allergic asthma subjects (n = 129)
exposed to different allergens in inhalation challenge tests. These tests were
performed using a standardized protocol as part of clinical trials of
experimental treatments for asthma, prior to drug randomization. Five allergen
types were represented: the house dust mites Dermatophagoides pteronyssinus and
Dermatophagoides farinae, ragweed, grass, and cat. RESULTS: Of 118 individuals
with a sputum sample collected before allergen challenge (baseline), 45 (38%) had
paucigranulocytic, 51 (43%) eosinophilic, 11 (9%) neutrophilic, and 11 (9%) mixed
granulocytic sputum. Of note, most individuals with baseline paucigranulocytic
sputum developed eosinophilic (48%) or mixed granulocytic (43%) sputum 7 hours
after allergen challenge, highlighting the dynamic nature of sputum inflammatory
subtype in asthma. Overall, there was no difference in the frequency of sputum
inflammatory subtypes following challenge with different allergen types. Similar
results were observed at 24 hours after allergen challenge. CONCLUSIONS: Unlike
reported in mice, in humans the sputum inflammatory subtype observed after an
allergen-induced asthma exacerbation is unlikely to be influenced by the type of
allergen used.
PMID- 29337346
TI - Effective role of medium supplementation in microalgal lipid accumulation.
AB - The present study investigated the interaction between starch and lipid
accumulation in a green microalgae enrichment culture. The objective was to
optimize the lipid content by manipulation of the medium in regular batch
culture. Two medium designs were evaluated: First a high ortho-P concentration
with vitamin supplementary (Pi-vitamins supplemented medium), second normal
growth medium (control). Both media contained a low amount of nitrogen which was
consumed during batch growth in three days. The batch experiments continued for
another 4 days with the absence of soluble nitrogen in the medium. When the mixed
microalgal culture was incubated in the Pi-vitamin supplemented medium, the
lipid, and starch content of the culture increased within the first 3 days to
102.0 +/- 5.2 mg/L (12.7 +/- 0.6% of DW) and 31.7 +/- 1.6 mg/L (4.0 +/- 0.2% of
DW), respectively. On the last day of the experiment, the lipid, and starch
content in Pi-vitamin medium increased to 663.1 +/- 32.5 mg/L (33.4 +/- 1.6% of
DW) and 127.5 +/- 5.2 mg/L (6.4 +/- 0.3% of DW). However, the lipid and starch
content in the control process, reached to 334.7 +/- 16.4 mg/L (20.1 +/- 1.0% of
DW) and 94.3 +/- 4.6 mg/L (5.7 +/- 0.3% of DW), respectively. The high Pi-vitamin
medium induced storing lipid formation clearly while the starch formation was not
affected. The lipid contents reported here are among the high reported in the
literature, note that already under full growth conditions significant lipid
levels occurred in the algal enrichment culture. The high lipid productivity of
the reported mixed microalgae culture provides an efficient route for efficient
algal biodiesel production.
PMID- 29337347
TI - A latent state-trait analysis of interoceptive accuracy.
AB - Interoceptive accuracy (IAc), that is, the ability to accurately perceive one's
own bodily signals, is widely assumed to be a trait, although experimental
manipulations such as stress may affect IAc. We used structural equation modeling
to estimate the reliability of IAc, and the proportions of individual differences
in IAc, explained by a trait and occasion-specific effects of situation and
person-situation interactions. We assessed IAc in 59 healthy participants (40
women, MAge = 23.4 years) on three consecutive measurement occasions,
approximately 1 week apart, in a rest and poststress condition, using a heartbeat
counting and a heartbeat discrimination task. The results showed fair temporal
stability (intraclass correlation coefficients >= 0.38) and good reliability (Mdn
= .63; range .49-.83) for both methods. While around 40% of the variance of a
single IAc measurement could be explained by a trait, approximately 27% was
accounted for by occasion-specific effects of situation and person-situation
interaction. These results suggest that IAc measures are relatively consistent
and that situations and person-situation interactions impact IAc as measured at a
certain point in time. An aggregation across at least two measurements is
recommended when using IAc as a trait variable.
PMID- 29337348
TI - Expression of the purine biosynthetic enzyme phosphoribosyl formylglycinamidine
synthase in neurons.
AB - Purines are metabolic building blocks essential for all living organisms on
earth. De novo purine biosynthesis occurs in the brain and appears to play
important roles in neural development. Phosphoribosyl formylglycinamidine
synthase (FGAMS, also known as PFAS or FGARAT), a core enzyme involved in the de
novo synthesis of purines, may play alternative roles in viral pathogenesis. To
date, no thorough investigation of the endogenous expression and localization of
de novo purine biosynthetic enzymes has been conducted in human neurons or in
virally infected cells. In this study, we characterized expression of FGAMS using
multiple neuronal models. In differentiated human SH-SY5Y neuroblastoma cells,
primary rat hippocampal neurons, and in whole-mouse brain sections, FGAMS
immunoreactivity was distributed within the neuronal cytoplasm. FGAMS
immunolabeling in vitro demonstrated extensive distribution throughout neuronal
processes. To investigate potential changes in FGAMS expression and localization
following viral infection, we infected cells with the human pathogen herpes
simplex virus 1. In infected fibroblasts, FGAMS immunolabeling shifted from a
diffuse cytoplasmic location to a mainly perinuclear localization by 12 h post
infection. In contrast, in infected neurons, FGAMS localization showed no
discernable changes in the localization of FGAMS immunoreactivity. There were no
changes in total FGAMS protein levels in either cell type. Together, these data
provide insight into potential purine biosynthetic mechanisms utilized within
neurons during homeostasis as well as viral infection. Cover Image for this
Issue: doi: 10.1111/jnc.14169.
PMID- 29337349
TI - Phytochemicals, Anti-Inflammatory, Antiproliferative, and Methylglyoxal Trapping
Properties of Zijuan Tea.
AB - : Zijuan tea (Camellia sinensis var. assamica) is a unique anthocyanin-rich tea
cultivar in China. Although chemical component analysis of Zijuan tea and
extraction technology of anthocyanins was widely documented, its functional
properties have not been extensively explored. In this study, the anti
inflammatory, antiproliferative, and methylglyoxal (MGO) trapping activities of
water extract (ZWE) and ethyl acetate extract (ZEE) of Zijuan tea were
investigated for the 1st time. Results showed that ZWE and ZEE exhibited
inhibitory effects on nitric oxide (NO), tumor necrosis factor (TNF)-alpha, and
interleukin (IL)-6 production as well as inducible nitric oxide synthase protein
(iNOS) expression in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages.
Moreover, Zijuan tea extracts exerted stronger antiproliferative activity against
HCT-116 cells compared with HepG2 and MDA-MB-231 cells, and thus could induce
apoptosis in HCT-116 cells in a dose-dependent manner. Furthermore, Zijuan tea
extracts were effective in trapping MGO under simulated physiological conditions,
and the T1/2 (the time for 50% MGO remaining) values of ZWE and ZEE were 3.69 and
6.20 min, respectively. Additionally, the contents of total phenolics and
catechins in ZEE were 685.43 +/- 16.00 and 454.96 +/- 4.21 mg/g extract,
respectively, and in ZWE were 422.59 +/- 12.09 and 307.29 +/- 0.85 mg/g extract,
respectively. Therefore, ZEE exhibited better anti-inflammatory,
antiproliferative, and MGO trapping properties than ZWE may be mainly attributed
to its higher (P < 0.05) content of total phenolics, expecially catechins. These
results suggest that Zijuan tea could be a potential natural resource for the
development of functional tea beverage. PRACTICAL APPLICATION: This study
revealed that Zijuan tea extracts possessed anti-inflammatory, antiproliferative,
and methylglyoxal trapping potentials in vitro. With high anthocyanins and
polyphenols, Zijuan tea can be developed into a healthy tea beverage or used as a
natural component to reduce the level of methylglyoxal in Maillard reaction.
PMID- 29337350
TI - Alterations in mGlu5 receptor expression and function in the striatum in a rat
depression model.
AB - Major depressive disorder is a common form of mental illness. Many brain regions
are implicated in the pathophysiology and symptomatology of depression. Among key
brain areas is the striatum that controls reward and mood and is involved in the
development of core depression-like behavior in animal models of depression.
While molecular mechanisms in this region underlying depression-related behavior
are poorly understood, the glutamatergic input to the striatum is believed to
play a role. In this study, we investigated changes in metabotropic glutamate
(mGlu) receptor expression and signaling in the striatum of adult rats in
response to prolonged (10-12 weeks) social isolation, a pre-validated animal
paradigm modeling depression in adulthood. We found that mGlu5 receptor protein
levels in the striatum were increased in rats that showed typical depression- and
anxiety-like behavior after chronic social isolation. This increase in mGlu5
receptor expression was seen in both subdivisions of the striatum, the nucleus
accumbens and caudate putamen. At subcellular and subsynaptic levels, mGlu5
receptor expression was elevated in surface membranes at synaptic sites. In
striatal neurons, the mGlu5-associated phosphoinositide signaling pathway was
augmented in its efficacy after prolonged social isolation. These data indicate
that the mGlu5 receptor is a sensitive substrate of depression. Adulthood social
isolation leads to the up-regulation of mGlu5 receptor expression and function in
striatal neurons.
PMID- 29337351
TI - Selection of Yeast Strains for Tequila Fermentation Based on Growth Dynamics in
Combined Fructose and Ethanol Media.
AB - : The high concentration of fructose in agave juice has been associated with
reduced ethanol tolerance of commercial yeasts used for tequila production and
low fermentation yields. The selection of autochthonous strains, which are better
adapted to agave juice, could improve the process. In this study, a 2-step
selection process of yeasts isolated from spontaneous fermentations for tequila
production was carried out based on analysis of the growth dynamics in combined
conditions of high fructose and ethanol. First, yeast isolates (605) were
screened to identify strains tolerant to high fructose (20%) and to ethanol
(10%), yielding 89 isolates able to grow in both conditions. From the 89
isolates, the growth curves under 8 treatments of combined fructose (from 20% to
5%) and ethanol (from 0% to 10%) were obtained, and the kinetic parameters were
analyzed with principal component analysis and k-means clustering. The resulting
yeast strain groups corresponded to the fast, medium and slow growers. A second
clustering of only the fast growers led to the selection of 3 Saccharomyces
strains (199, 230, 231) that were able to grow rapidly in 4 out of the 8
conditions evaluated. This methodology differentiated strains phenotypically and
could be further used for strain selection in other processes. PRACTICAL
APPLICATION: A method to select yeast strains for fermentation taking into
account the natural differences of yeast isolates. This methodology is based on
the cell exposition to combinations of sugar and ethanol, which are the most
important stress factors in fermentation. This strategy will help to identify the
most tolerant strain that could improve ethanol yield and reduce fermentation
time.
PMID- 29337352
TI - Genetic removal of eIF2alpha kinase PERK in mice enables hippocampal L-LTP
independent of mTORC1 activity.
AB - Characterization of the molecular signaling pathways underlying protein synthesis
dependent forms of synaptic plasticity, such as late long-term potentiation (L
LTP), can provide insights not only into memory expression/maintenance under
physiological conditions but also potential mechanisms associated with the
pathogenesis of memory disorders. Here, we report in mice that L-LTP failure
induced by the mammalian (mechanistic) target of rapamycin complex 1 (mTORC1)
inhibitor rapamycin is reversed by brain-specific genetic deletion of PKR-like ER
kinase, PERK (PERK KO), a kinase for eukaryotic initiation factor 2alpha
(eIF2alpha). In contrast, genetic removal of general control non-derepressible-2,
GCN2 (GCN2 KO), another eIF2alpha kinase, or treatment of hippocampal slices with
the PERK inhibitor GSK2606414, does not rescue rapamycin-induced L-LTP failure,
suggesting mechanisms independent of eIF2alpha phosphorylation. Moreover, we
demonstrate that phosphorylation of eukaryotic elongation factor 2 (eEF2) is
significantly decreased in PERK KO mice but unaltered in GCN2 KO mice or slices
treated with the PERK inhibitor. Reduction in eEF2 phosphorylation results in
increased general protein synthesis, and thus could contribute to the mTORC1
independent L-LTP in PERK KO mice. We further performed experiments on mutant
mice with genetic removal of eEF2K (eEF2K KO), the only known kinase for eEF2,
and found that L-LTP in eEF2K KO mice is insensitive to rapamycin. These data,
for the first time, connect reduction in PERK activity with the regulation of
translation elongation in enabling L-LTP independent of mTORC1. Thus, our
findings indicate previously unrecognized levels of complexity in the regulation
of protein synthesis-dependent synaptic plasticity. Read the Editorial Highlight
for this article on page 119. Cover Image for this issue: doi: 10.1111/jnc.14185.
PMID- 29337353
TI - Consumer Acceptance Comparison Between Seasoned and Unseasoned Vegetables.
AB - : Recent findings show that approximately 87% of the U.S. population fail to meet
the vegetable intake recommendations, with unpleasant taste of vegetables being
listed as the primary reason for this shortfall. In this study, spice and herb
seasoning was used to enhance palatability of vegetables, in order to increase
consumer acceptance. In total, 749 panelists were screened and recruited as
specific vegetable likers of the vegetable being tested or general vegetable
likers. Four sessions were designed to evaluate the effect of seasoning within
each type of vegetable, including broccoli, cauliflower, carrot, and green bean.
Each panelist was only allowed to participate in one test session to evaluate
only one vegetable type, so as to mitigate potential learning effect. Overall,
the results showed that seasoned vegetables were significantly preferred over
unseasoned vegetables (P < 0.001), indicating the sensory properties were
significantly improved with seasoning. When general vegetable likers and specific
vegetable likers were compared in terms of their preference between seasoned and
unseasoned vegetables, the pattern varied across different vegetables; however,
general trend of seasoned vegetable being preferred remained. The findings from
this study demonstrate the effect of seasoning in enhancing consumer liking of
vegetables, which may lead to increased consumption to be assessed in future
studies. PRACTICAL APPLICATION: To improve the sensory properties of vegetables,
masking the bitter taste of vegetables using spice and herb seasoning are gaining
increasing attention. Our findings suggest that the overall liking of vegetables
could be improved by incorporating spice and herb seasonings that are
specifically formulated for each vegetable. Ultimately, developing and
commercializing spice and herb seasonings may aid to increase vegetable
consumption, as well as expanding the vegetable seasoning market.
PMID- 29337354
TI - Current spring warming as a driver of selection on reproductive timing in a wild
passerine.
AB - Evolutionary adaptation as a response to climate change is expected for fitness
related traits affected by climate and exhibiting genetic variance. Although the
relationship between warmer spring temperature and earlier timing of reproduction
is well documented, quantifications and predictions of the impact of global
warming on natural selection acting on phenology in wild populations remain rare.
If global warming affects fitness in a similar way across individuals within a
population, or if fitness consequences are independent of phenotypic variation in
key-adaptive traits, then no evolutionary response is expected for these traits.
Here, we quantified the selection pressures acting on laying date during a 24
year monitoring of blue tits in southern Mediterranean France, a hot spot of
climate warming. We explored the temporal fluctuation in annual selection
gradients and we determined its temperature-related drivers. We first
investigated the month-specific warming since 1970 in our study site and tested
its influence on selection pressures, using a model averaging approach. Then, we
quantified the selection strength associated with temperature anomalies
experienced by the blue tit population. We found that natural selection acting on
laying date significantly fluctuated both in magnitude and in sign across years.
After identifying a significant warming in spring and summer, we showed that
warmer daily maximum temperatures in April were significantly associated with
stronger selection pressures for reproductive timing. Our results indicated an
increase in the strength of selection by 46% for every +1 degrees C anomaly. Our
results confirm the general assumption that recent climate change translates into
strong selection favouring earlier breeders in passerine birds. Our findings also
suggest that differences in fitness among individuals varying in their breeding
phenology increase with climate warming. Such climate-driven influence on the
strength of directional selection acting on laying date could favour an adaptive
response in this trait, since it is heritable.
PMID- 29337355
TI - Moisture Adsorption Isotherm and Storability of Hazelnut Inshells and Kernels
Produced in Oregon, USA.
AB - : Moisture adsorption isotherms and storability of dried hazelnut inshells and
kernels produced in Oregon were evaluated and compared among cultivars, including
Barcelona, Yamhill, and Jefferson. Experimental moisture adsorption data fitted
to Guggenheim-Anderson-de Boer (GAB) model, showing less hygroscopic properties
in Yamhill than other cultivars of inshells and kernels due to lower content of
carbohydrate and protein, but higher content of fat. The safe levels of moisture
content (MC, dry basis) of dried inshells and kernels for reaching kernel water
activity (aw ) <=0.65 were estimated using the GAB model as 11.3% and 5.0% for
Barcelona, 9.4% and 4.2% for Yamhill, and 10.7% and 4.9% for Jefferson,
respectively. Storage conditions (2 degrees C at 85% to 95% relative humidity
[RH], 10 degrees C at 65% to 75% RH, and 27 degrees C at 35% to 45% RH), times
(0, 4, 8, or 12 mo), and packaging methods (atmosphere vs. vacuum) affected MC,
aw , bioactive compounds, lipid oxidation, and enzyme activity of dried hazelnut
inshells or kernels. For inshells packaged at woven polypropylene bag, MC and aw
of inshells and kernels (inside shells) increased at 2 and 10 degrees C, but
decreased at 27 degrees C during storage. For kernels, lipid oxidation and
polyphenol oxidase activity also increased with extended storage time (P < 0.05),
and MC and aw of vacuum packaged samples were more stable during storage than
those atmospherically packaged ones. Principal component analysis showed
correlation of kernel qualities with storage condition, time, and packaging
method. This study demonstrated that the ideal storage condition or packaging
method varied among cultivars due to their different moisture adsorption and
physicochemical and enzymatic stability during storage. PRACTICAL APPLICATION:
Moisture adsorption isotherm of hazelnut inshells and kernels is useful for
predicting the storability of nuts. This study found that water adsorption and
storability varied among the different cultivars of nuts, in which Yamhill was
less hygroscopic than Barcelona and Jefferson, thus more stable during storage.
For ensuring food safety and quality of nuts during storage, each cultivar of
kernels should be dried to a certain level of MC. Lipid oxidation and enzyme
activity of kernel could be increased with extended storage time. Vacuum
packaging was recommended to kernels for reducing moisture adsorption during
storage.
PMID- 29337356
TI - Stabilizing selection on sperm number revealed by artificial selection and
experimental evolution.
AB - Sperm competition is taxonomically widespread in animals and is usually
associated with large sperm production, being the number of sperm in the
competing pool the prime predictor of fertilization success. Despite the strong
postcopulatory selection acting directionally on sperm production, its genetic
variance is often very high. This can be explained by trade-offs between sperm
production and traits associated with mate acquisition or survival, that may
contribute to generate an overall stabilizing selection. To investigate this
hypothesis, we first artificially selected male guppies (Poecilia reticulata) for
high and low sperm production for three generations, while simultaneously
removing sexual selection. Then, we interrupted artificial selection and restored
sexual selection. Sperm production responded to divergent selection in one
generation, and when we restored sexual selection, both high and low lines
converged back to the mean sperm production of the original population within two
generations, indicating that sperm number is subject to strong stabilizing total
sexual selection (i.e., selection acting simultaneously on all traits associated
with reproductive success). We discuss the possible mechanisms responsible for
the maintenance of high genetic variability in sperm production despite strong
selection acting on it.
PMID- 29337363
TI - Inhibition of apoptosis using exosomes in Chinese hamster ovary cell culture.
AB - Animal cell culture technology for therapeutic protein production has shown
significant improvement over the last few decades. Chinese hamster ovary (CHO)
cells have been widely adapted for the production of biopharmaceutical drugs. In
the biopharmaceutical industry, it is crucial to develop cell culture media and
culturing conditions to achieve the highest productivity and quality. However,
CHO cells are significantly affected by apoptosis in the bioreactors, resulting
in a substantial decrease in product quantity and quality. Thus, to overcome the
obstacle of apoptosis in CHO cell culture, it is critical to develop a novel
method that does not have minimal concern of safety or cost. Herein, we showed
for the first time that exosomes, which are nano-sized extracellular vesicles,
derived from CHO cells inhibited apoptosis in CHO cell culture when supplemented
to the culture medium. Flow cytometric and microscopic analyses revealed that
substantial amounts of exosomes were delivered to CHO cells. Higher cell
viability after staurosporine treatment was observed by exosome supplementation
(67.3%) as compared to control (41.1%). Furthermore, exosomes prevented the
mitochondrial membrane potential loss and caspase-3 activation, meaning that the
exosomes enhanced cellular activities under pro-apoptotic condition. As the
exosomes supplements are derived from CHO cells themselves, it is not only
beneficial for the biopharmaceutical productivity of CHO cell culture to inhibit
apoptosis, but also from a regulatory standpoint to diminish any safety concerns.
Thus, we conclude that the method developed in this research may contribute to
the biopharmaceutical industry where minimizing apoptosis in CHO cell culture is
beneficial.
PMID- 29337364
TI - The Function of Emulsions on the Biogenic Amine Formation and their Indices of
Sea Bass Fillets (Dicentrarchus Labrax) Stored in Vacuum Packaging.
AB - : The impacts of emulsions based on commercial oils on the biogenic amine
formation and their indices of vacuumed packed sea bass fillets were
investigated. The results showed that among biogenic amines, cadaverine,
putrescine, spermidine, spermine, serotonin, dopamine, and agmatine were
predominant amines in sea bass fillets stored under vacuum packaging. Significant
differences (P < 0.05) in biogenic amines concentrations of vacuumed packed sea
bass treated with emulsions were observed. All groups contained histamine lower
than 5.0 mg/100 g, regarded as the allowable limit by the U.S. Food and Drug
Administration. Polyamine levels were not affected by application of emulsion.
Quality index (QI) showed an increase and after 14 d of storage it decreased in
all groups. The control generally seemed to higher QI value than those of
treatment groups except at 14 and 18 days while soybean and corn gave lower QI
among treatment groups. Only biogenic amine index correlated with sensory
acceptability of vacuumed packed sea bass, indicating that this index can be used
for determination of the degree of spoilage of vacuumed packed sea bass.
Emulsions extended the shelf-life (approximately 2 to 4 d) of vacuumed packed sea
bass fillets by inhibiting microbial growth compared to the control. PRACTICAL
APPLICATION: Emulsions have become popular since they are regarded as ideal
carrier for the delivery of lipophilic substances due to the ease of preparation,
small particle size, their enhanced bioavailability, and long term kinetic
stability. They have been proven to be self-preserving antimicrobials due to
bound water in their structure and thus no available water to microorganisms.
Antimicrobial emulsions have potential applications in many fields because they
are inexpensive, stable, and nontoxic agents.
PMID- 29337365
TI - Loss of STI1-mediated neuronal survival and differentiation in disease-associated
mutations of prion protein.
AB - Cellular prion protein (PrPC ) is widely expressed and displays a variety of well
described functions in the central nervous system (CNS). Mutations of the PRNP
gene are known to promote genetic human spongiform encephalopathies, but the
components of gain- or loss-of-function mutations to PrPC remain a matter for
debate. Among the proteins described to interact with PrPC is Stress-inducible
protein 1 (STI1), a co-chaperonin that is secreted from astrocytes and triggers
neuroprotection and neuritogenesis through its interaction with PrPC . In this
work, we evaluated the impact of different PrPC pathogenic point mutations on
signaling pathways induced by the STI1-PrPC interaction. We found that some of
the pathogenic mutations evaluated herein induce partial or total disruption of
neuritogenesis and neuroprotection mediated by mitogen-activated protein kinase
(MAPK)/extracellular signal-regulated kinases 1 and 2 (ERK1/2) and protein kinase
A (PKA) signaling triggered by STI1-PrPC engagement. A pathogenic mutant PrPC
that lacked both neuroprotection and neuritogenesis activities fail to promote
negative dominance upon wild-type PrPC . Also, a STI1-alpha7-nicotinic
acetylcholine receptor-dependent cellular signaling was present in a PrPC mutant
that maintained both neuroprotection and neuritogenesis activities similar to
what has been previously observed by wild-type PrPC . These results point to a
loss-of-function mechanism underlying the pathogenicity of PrPC mutations.
PMID- 29337366
TI - Replenishment of Docosahexaenoic Acid (DHA) in Dietary n-3-Deficient Mice Fed DHA
in Triglycerides or Phosphatidylcholines After Weaning.
AB - : Previous studies have shown that DHA in triglyceride (TG) and
phosphatidylcholine (PC) forms are different in their bioavailability. The aim of
this study was to investigate the comparative effects of DHA-TG and DHA-PC on
tissue DHA accretion in dietary n-3 polyunsaturated fatty acid deficient (n-3
Def) mice. The mice were fed with n-3 Def diet containing DHA-TG or DHA-PC (5
g/kg diet) for 2, 4, 7, or 14 d after weaning, respectively. The DHA levels in
the cortex, liver, testis, and erythrocytes were analyzed by gas chromatography.
For liver, DHA mainly existed in hepatic phospholipids relative to triglycerides.
Both DHA-TG and DHA-PC could recover the hepatic DHA to a normal level.
Interestingly, DHA-TG was more effective in increasing the DHA level in hepatic
triglycerides, and DHA-PC was more effective in increasing the DHA level in
hepatic phospholipids. For erythrocytes, during the first 7 d, no difference was
observed after dietary DHA-TG and DHA-PC but a significantly higher DHA
percentage was detected in the DHA-PC group after 14 d. For cortex, the DHA-TG
group showed a higher cortical DHA level at the 4th day, but the DHA-PC group
showed a higher cortical DHA level with a greater slope from Day 7 to Day 14, and
the same trend was observed in testis. But unexpectedly, the DHA level in testis
showed a downtrend from Day 7 to Day 14. This study suggests that, under dietary
n-3-deficient condition, both DHA-TG and DHA-PC could recover the DHA level in
tissues after weaning, and DHA-PC showed a better supplemental effect. PRACTICAL
APPLICATION: Dietary DHA is essential for neurodevelopment which is usually
accompanied by large amounts of DHA accretion in the brain. Our present study
showed that DHA-PC had a better efficiency for DHA accretion in the brain and
other tissues compared with DHA-TG. The findings are supposed to pave the way for
the DHA in phospholipids as a novel nutrient added into the infant formula and
assisted food for neurodevelopment.
PMID- 29337367
TI - Correlation of simulation/finite element analysis to the separation of
intrinsically magnetic spores and red blood cells using a microfluidic magnetic
deposition system.
AB - Magnetic separation of cells has been, and continues to be, widely used in a
variety of applications, ranging from healthcare diagnostics to detection of food
contamination. Typically, these technologies require cells labeled with antibody
magnetic particle conjugate and a high magnetic energy gradient created in the
flow containing the labeled cells (i.e., a column packed with magnetically
inducible material), or dense packing of magnetic particles next to the flow
cell. Such designs, while creating high magnetic energy gradients, are not
amenable to easy, highly detailed, mathematic characterization. Our laboratories
have been characterizing and developing analysis and separation technology that
can be used on intrinsically magnetic cells or spores which are typically orders
of magnitude weaker than typically immunomagnetically labeled cells. One such
separation system is magnetic deposition microscopy (MDM) which not only
separates cells, but deposits them in specific locations on slides for further
microscopic analysis. In this study, the MDM system has been further
characterized, using finite element and computational fluid mechanics software,
and separation performance predicted, using a model which combines: 1) the
distribution of the intrinsic magnetophoretic mobility of the cells (spores); 2)
the fluid flow within the separation device; and 3) accurate maps of the values
of the magnetic field (max 2.27 T), and magnetic energy gradient (max of 4.41 T2
/mm) within the system. Guided by this model, experimental studies indicated that
greater than 95% of the intrinsically magnetic Bacillus spores can be separated
with the MDM system. Further, this model allows analysis of cell trajectories
which can assist in the design of higher throughput systems.
PMID- 29337368
TI - Stability and Antioxidant Activity of Annatto (Bixa orellana L.) Tocotrienols
During Frying and in Fried Tortilla Chips.
AB - : Annatto tocotrienols (AnT3), which contain approximately 90% delta-tocotrienol
(delta-T3), were added to mid-oleic sunflower oil used for frying tortilla chips
over 3 d. The objectives were to evaluate their stability during frying,
absorption by the fried food, and activity as antioxidants in frying oil and in
tortilla chips during storage. AnT3 did not significantly affect the stability of
the oil during frying or the sensory profiles of freshly fried chips. The
naturally present alpha-tocopherol (alpha-T) in the oil degraded at a lower rate
in the presence of AnT3, resulting in significantly higher alpha-T by the end of
the frying study. Levels of tocopherols and tocotrienols in the chips mirrored
oil levels. AnT3 did not affect the sensory profile of the chips after 1 wk of
storage at 50 degrees C, but after 3 wk of storage, the control chips had higher
levels of painty and rancid flavors compared to chips with AnT3. Headspace
hexanal was also significantly higher in the control chips compared to the chips
with AnT3 after 3 wk of storage. PRACTICAL APPLICATION: Annatto tocotrienols,
containing primarily delta- and gamma-tocotrienols, were added to mid-oleic
sunflower oil used for frying tortilla chips. The tocotrienols were absorbed by
the chips along with the oil. They slowed the degradation of alpha tocopherol
during frying, and reduced levels of painty and rancid flavor scores as well as
headspace hexanal in chips that were stored for 3 wk at elevated temperatures.
The results indicated that fried snack foods such as tortilla chips may be a
suitable and convenient vehicle for enriching tocotrienols in the diet, and that
tocotrienols may also enhance the shelf-life of fried foods.
PMID- 29337369
TI - Hepatoprotective Effects of the Honey of Apis cerana Fabricius on Bromobenzene
Induced Liver Damage in Mice.
AB - Apis cerana honey (honey of Apis cerana Fabricius), widely distributed in the
mountain areas of East Asia, has not been studied fully. The hepatoprotective
activity of A. cerana honey was evaluated against bromobenzene-induced liver
damage in mice. In high dose, A. cerana honey can significantly alleviate liver
injury, as is indicated by the depressed levels of serum alanine aminotransferase
(ALT) (59.13%) and aspartate aminotransferase (AST) (79.71%), the inhibited
malondialdehyde (MDA) content (63.30%), the elevated activities of superoxide
dismutase (SOD) (73.12%) and glutathione-Px (57.24%), and the decreased
expression of Transforming growth factor beta1 (51.83%) induced by bromobenzene
(P < 0.05). The quantitative analysis of twelve major constituents (1 to 12) of
A. cerana honey was executed by high performance liquid chromatography-diode
array detector. The results indicate that treatment with A. cerana honey can
prevent bromobenzene-induced hepatic damage in mice. Polyphenols might be the
bioactive substances attributed to its antioxidant properties and intervention of
oxidative stress.
PMID- 29337371
TI - Avian Retrovirus-Mediated Tumor-Specific Gene Knockout.
AB - The RCAS (replication-competent avian sarcoma leukosis virus long-terminal repeat
with splice acceptor)-TVA (tumor virus A) gene delivery system has been
successfully used in modeling human cancers. Based on this, we have recently
developed a novel RCI-Oncogene (RCAS-Cre-IRES-Oncogene) gene delivery system that
can be used to efficiently manipulate gene expression in spontaneous tumors in
vivo. We used this system for tumor gene knockout (TuKO) and demonstrated a
crucial role of FGFR1 in driving mammary tumor metastasis. This versatile tumor
gene modification system can also be adapted into different configurations to
address different questions in appropriate mutant mouse hosts. Here we describe a
protocol using the TuKO approach to knock out a gene of interest in tumors in
appropriate hosts. (c) 2018 by John Wiley & Sons, Inc.
PMID- 29337370
TI - Modulating Gene Expression in Epstein-Barr Virus (EBV)-Positive B Cell Lines with
CRISPRa and CRISPRi.
AB - Epstein-Barr virus (EBV) transforms small resting primary B cells into large
lymphoblastoid cells which are able to grow and survive in vitro indefinitely.
These cells represent a model for oncogenesis. In this unit, variants of
conventional clustered regularly interspaced short palindromic repeats (CRISPR),
namely the CRISPR activation (CRISPRa) and CRISPR interference (CRISPRi) methods,
are discussed in the context of gene regulation at genomic DNA promoter and
enhancer elements. Lymphoblastoid B cell lines (LCLs) stably expressing nuclease
deficient Cas9 (dCas9)-VP64 (Cas9 associated with CRISPRa) or dCas9-KRAB (Cas9
associated with CRISPRi) are transduced with lentivirus that encodes a single
guide RNA (sgRNA) that targets a specific gene locus. The ribonucleoprotein
complex formed by the dCas9 molecule and its cognate sgRNA enables sequence
specific binding at a promoter or enhancer of interest to affect the expression
of genes regulated by the targeted promoter or enhancer. (c) 2018 by John Wiley &
Sons, Inc.
PMID- 29337372
TI - CRISPR-Cas9-Edited Site Sequencing (CRES-Seq): An Efficient and High-Throughput
Method for the Selection of CRISPR-Cas9-Edited Clones.
AB - The emergence of clustered regularly interspaced short palindromic repeats-Cas9
(CRISPR-Cas9) gene editing systems has enabled the creation of specific mutants
at low cost, in a short time and with high efficiency, in eukaryotic cells. Since
a CRISPR-Cas9 system typically creates an array of mutations in targeted sites, a
successful gene editing project requires careful selection of edited clones. This
process can be very challenging, especially when working with multiallelic genes
and/or polyploid cells (such as cancer and plants cells). Here we described a
next-generation sequencing method called CRISPR-Cas9 Edited Site Sequencing (CRES
Seq) for the efficient and high-throughput screening of CRISPR-Cas9-edited
clones. CRES-Seq facilitates the precise genotyping up to 96 CRISPR-Cas9-edited
sites (CRES) in a single MiniSeq (Illumina) run with an approximate sequencing
cost of $6/clone. CRES-Seq is particularly useful when multiple genes are
simultaneously targeted by CRISPR-Cas9, and also for screening of clones
generated from multiallelic genes/polyploid cells. (c) 2018 by John Wiley & Sons,
Inc.
PMID- 29337373
TI - Making Use of Cancer Genomic Databases.
AB - The vast amounts of genomic data now deposited in public repositories represent
rich resources for cancer researchers. Large-scale genomics initiatives such as
The Cancer Genome Atlas have made available data from multiple molecular
profiling platforms (e.g., somatic mutation, RNA and protein expression, and DNA
methylation) for the same set of over 10,000 human tumors. There has been much
collective effort toward providing user-friendly software tools for biologists
lacking computational skills to ask questions of large-scale genomic datasets. At
the same time, there remains a clear need for skilled bioinformatics analysts to
answer the types of questions that cannot easily be addressed using the public
user-friendly software tools. This overview introduces the reader to the many
resources available for working with cancer genomic databases. (c) 2018 by John
Wiley & Sons, Inc.
PMID- 29337374
TI - Pooled Lentiviral-Delivery Genetic Screens.
AB - Pooled cell-based screens of mammalian genetic perturbations enable systematic
large-scale, even genome-scale, evaluation of gene function. Pooled screens
introduce genetic perturbations into a cell population through viral transduction
such that each cell integrates into its DNA a single or small number of library
perturbations with barcodes identifying the perturbations. One then selects and
physically isolates the subset of cells that exhibit the phenotype of interest.
Sequencing the barcodes in the hit cells reveals which genes favored or inhibited
the hit phenotype. Various genetic perturbations are possible, including CRISPR
gene knockout, ectopic gene expression, and RNA interference. Regardless of the
type of library being screened or the type of cell model being tested, such
screens involve many common steps and procedures. This unit describes detailed
experimental protocols for the key steps, and also highlights some of the key
factors to achieving a well-powered, reproducible screen result. (c) 2018 by John
Wiley & Sons, Inc.
PMID- 29337375
TI - Transfection by Electroporation.
AB - Electroporation-the use of high-voltage electric shocks to introduce DNA into
cells-can be used with most cell types, yields a high frequency of both stable
transformation and transient gene expression, and, because it requires fewer
steps, can be easier than alternate techniques. This unit describes
electroporation of mammalian cells, including ES cells for the preparation of
knock-out, knock-in, and transgenic mice. Protocols are described for the use of
electroporation in vivo to perform gene therapy for cancer therapy and DNA
vaccination. Also described are modifications for preparation and transfection of
plant protoplasts. (c) 2018 by John Wiley & Sons, Inc.
PMID- 29337376
TI - CRISPR/Cas9-Mediated Genome Editing in Epstein-Barr Virus-Transformed
Lymphoblastoid B-Cell Lines.
AB - Epstein-Barr virus (EBV) efficiently transforms primary human B cells into
immortalized lymphoblastoid cell lines (LCLs), which are extensively used in
human genetic, immunological and virological studies. LCLs provide unlimited
sources of DNA for genetic investigation, but can be difficult to manipulate, for
instance because low retroviral or lentiviral transduction frequencies hinder
experiments that require co-expression of multiple components. This unit details
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9
engineering for robust LCL genome editing. We describe the generation and
delivery of single-guide RNAs (sgRNAs), or dual-targeting sgRNAs, via lentiviral
transduction of LCLs that stably express Cas9 protein. CRISPR/Cas9 editing allows
LCL loss-of-function studies, including knock-out of protein-coding genes or
deletion of DNA regulatory elements, and can be adapted for large-scale screening
approaches. Low transfection efficiencies are a second barrier to performing
CRISPR editing in LCLs, which are not typically lipid-transfectable. To
circumvent this barrier, we provide an optimized protocol for LCL nucleofection
of Cas9/sgRNA ribonucleoprotein complexes (RNPs) as an alternative route to
achieve genome editing in LCLs. These editing approaches can also be employed in
other B-cell lines, including Burkitt lymphoma and diffuse large B-cell lymphoma
cells, and are highly reproducible. (c) 2018 by John Wiley & Sons, Inc.
PMID- 29337377
TI - Ultrafast Laser-Shock-Induced Confined Metaphase Transformation for Direct
Writing of Black Phosphorus Thin Films.
AB - Few-layer black phosphorus (BP) has emerged as one of the most promising
candidates for post-silicon electronic materials due to its outstanding
electrical and optical properties. However, lack of large-scale BP thin films is
still a major roadblock to further applications. The most widely used methods for
obtaining BP thin films are mechanical exfoliation and liquid exfoliation.
Herein, a method of directly synthesizing continuous BP thin films with the
capability of patterning arbitrary shapes by employing ultrafast laser writing
with confinement is reported. The physical mechanism of confined laser metaphase
transformation is understood by molecular dynamics simulation. Ultrafast laser
ablation of BP layer under confinement can induce transient nonequilibrium high
temperature and high-pressure conditions for a few picoseconds. Under optimized
laser intensity, this process induces a metaphase transformation to form a
crystalline BP thin film on the substrate. Raman spectroscopy, atomic force
microscopy, and transmission electron microscopy techniques are utilized to
characterize the morphology of the resulting BP thin films. Field-effect
transistors are fabricated on the BP films to study their electrical properties.
This unique approach offers a general methodology to mass produce large-scale
patterned BP films with a one-step manufacturing process that has the potential
to be applied to other 2D materials.
PMID- 29337378
TI - Resemblance of a model species and its mimic: Response to Bury and Cichon.
PMID- 29337379
TI - Interleukin-17A and vascular remodelling in severe asthma; lack of evidence for a
direct role.
AB - BACKGROUND: Bronchial vascular remodelling may contribute to the severity of
airway narrowing through mucosal congestion. Interleukin (IL)-17A is associated
with the most severe asthmatic phenotype but whether it might contribute to
vascular remodelling is uncertain. OBJECTIVE: To assess vascular remodelling in
severe asthma and whether IL-17A directly or indirectly may cause endothelial
cell activation and angiogenesis. METHODS: Bronchial vascularization was
quantified in asthmatic subjects, COPD and healthy subjects together with the
number of IL-17A+ cells as well as the concentration of angiogenic factors in the
sputum. The effect of IL-17A on in vitro angiogenesis, cell migration and
endothelial permeability was assessed directly on primary human lung
microvascular endothelial cells (HMVEC-L) or indirectly with conditioned medium
derived from normal bronchial epithelial cells (NHBEC), fibroblasts (NHBF) and
airway smooth muscle cells (ASMC) after IL-17A stimulation. RESULTS: Severe
asthmatics have increased vascularity compared to the other groups, which
correlates positively with the concentrations of angiogenic factors in sputum.
Interestingly, we demonstrated that increased bronchial vascularity correlates
positively with the number of subepithelial IL-17A+ cells. However IL-17A had no
direct effect on HMVEC-L function but it enhanced endothelial tube formation and
cell migration through the production of angiogenic factors by NHBE and ASMC.
CONCLUSIONS & CLINICAL RELEVANCE: Our results shed light on the role of IL-17A in
vascular remodelling, most likely through stimulating the synthesis of other
angiogenic factors. Knowledge of these pathways may aid in the identification of
new therapeutic targets.
PMID- 29337380
TI - Recent Advances in Micro-/Nanostructured Metal-Organic Frameworks towards
Photonic and Electronic Applications.
AB - Micro- and nanometer-sized metal-organic frameworks (MOFs) materials have
attracted great attention due to their unique properties and various potential
applications in photonics, electronics, high-density storage, chemo-, and
biosensors. The study of these materials supplies insight into how the crystal
structure, molecular components, and micro-/nanoscale effects can influence the
performance of inorganic-organic hybrid materials. In this Minireview article, we
introduce recent breakthroughs in the controlled synthesis of MOF micro
/nanomaterials with specific structures and compositions, the tunable photonic
and electronic properties of which would provide a novel platform for
multifunctional applications. Firstly, the design strategies for MOFs based on
self-assembly and crystal engineering principles are introduced. Attention is
then focused on the methods of fabrication of low-dimensional MOF micro
/nanostructures. Their new applications including two-photon excited
fluorescence, multi-photon pumped lasing, optical waveguides, nonlinear optical
(NLO), and field-effect transistors are also outlined. Finally, we briefly
discuss perspectives on the further development of these hybrid crystalline micro
/nanomaterials.
PMID- 29337381
TI - A Combined Photochemical and Multicomponent Reaction Approach to Precision
Oligomers.
AB - We introduce the convergent synthesis of linear monodisperse sequence-defined
oligomers through a unique approach, combining the Passerini three-component
reaction (P-3CR) and a Diels-Alder (DA) reaction based on photocaged dienes. A
set of oligomers is prepared resting on a Passerini linker unit carrying an
isocyano group for chain extension by P-3CR and a maleimide moiety for photoenol
conjugation enabling a modular approach for chain growth. Monodisperse oligomers
are accessible in a stepwise fashion by switching between both reaction types.
Employing sebacic acid as a core unit allows the synthesis of a library of
symmetric sequence-defined oligomers. The oligomers consist of alternating P-3CR
and photoblocks with molecular weights up to 3532.16 g mol-1 , demonstrating the
successful switching from P-3CR to photoenol conjugation. In-depth
characterization was carried out including size-exclusion chromatography (SEC),
high-resolution electrospray ionization mass spectrometry (ESI-MS) and NMR
spectroscopy, evidencing the monodisperse nature of the precision oligomers.
PMID- 29337382
TI - Frailty in patients with acute myeloid leukaemia, conceptual misapprehension of
chronological age.
AB - In haematology practice, patients with acute myeloid leukaemia (AML) are
generally assessed for frailty only if they are older and not able to tolerate
intensive and remission targeted treatments. We aimed to focus on frailty in
patients with AML, in all ages and aimed to evaluate its role and practicality in
daily routine. Data of patients diagnosed and treated for AML between 2006 and
2016 are recorded and assessed for their survival predictivity. One hundred and
ninety-seven patients were <65 years of age and 175 were >=65. Majority of the
younger patients showed ECOG 2 performance (119, 60.4%). Combined with ECOG
scale, G8 scale showed survival predictivity in younger patients as well as older
patients. Nutritional status showed a strong predictivity in younger patients
while remained insignificant in older patients. VES13 scale showed similar
predictivity strength for survival in both age groups (p = .001). Young AML
patients should be thoroughly evaluated as older patients. ECOG performance
evaluation should be supported with further scales. Young patients with lower
ECOG scores may be regarded as vulnerable with scales embracing dimensions such
as nutrition, perception of disease, depression and cognition. Nutrition should
be within the main goals of intensive treatment and is related with survival.
PMID- 29337383
TI - Pregnancy in Diabetes: challenges and opportunities for improving pregnancy
outcomes.
AB - Our aim was to review the data from the National Pregnancy in Diabetes (NPID)
audit, and to identify the challenges and opportunities for improving pregnancy
outcomes in women with diabetes. We reviewed three years of NPID data and
relevant diabetes and obstetric literature, and found that there has been little
change in pregnancy preparation or outcomes over the past 3 years, with
substantial clinic-to clinic variations in care. Women with Type 2 diabetes
remain less likely to take 5 mg preconception folic acid (22.8% vs. 41.8%; P <
0.05), and more likely to take potentially harmful medications (statin and/or ACE
inhibitor 13.0% vs. 1.8%; P < 0.05) than women with Type 1 diabetes. However,
women with Type 1 diabetes are less likely to achieve the recommended glucose
control target of HbA1c < 48 mmol/mol (6.5%) (14.9% vs. 38.1%; P < 0.05). The
following opportunities for improvement were identified. First, the need to
integrate reproductive health into the diabetes care plans of all women with
diabetes aged 15-50 years. Second, to develop more innovative approaches to
improve uptake of pre-pregnancy care in women with Type 2 diabetes in primary
care settings. Third, to integrate insulin pump, continuous glucose monitoring
and automated insulin delivery technologies into the pre-pregnancy and antenatal
care of women with Type 1 diabetes. Fourth, to improve postnatal care with
personalized approaches targeting women with previous pregnancy loss, congenital
anomaly and perinatal mortality. A nationwide commitment to delivering integrated
reproductive and diabetes healthcare interventions is needed to improve the
health outcomes of women with diabetes.
PMID- 29337384
TI - Dual-hormone artificial pancreas: benefits and limitations compared with single
hormone systems.
AB - Technological advances have made the artificial pancreas a reality. This has the
potential to improve the lives of individuals with Type 1 diabetes by reducing
the risk of hypoglycaemia, achieving better overall glucose control, and
enhancing quality of life. Both single-hormone (insulin-only) and dual-hormone
(insulin and glucagon) systems have been developed; however, a focused review of
the relative benefits of each artificial pancreas system is needed. We reviewed
studies that directly compared single- and dual-hormone systems to evaluate the
efficacy of each system for preventing hypoglycaemia and maintaining glycaemic
control, as well as their utility in specific situations including during
exercise, overnight and during the prandial period. We observed additional
benefits with the dual-hormone artificial pancreas for reducing the risk of
hypoglycaemic events overall and during exercise over the study duration. The
single-hormone artificial pancreas was sufficient for maintenance of euglycaemia
in the overnight period and for preventing late-onset post-exercise
hypoglycaemia. Future comparative studies of longer duration are required to
determine whether one system is superior for improving mean glucose control,
eliminating severe hypoglycaemia, or improving quality of life.
PMID- 29337385
TI - Orientation-Dependent Strain Relaxation and Chemical Functionalization of
Graphene on a Cu(111) Foil.
AB - Epitaxial graphene grown on single crystal Cu(111) foils by chemical vapor
deposition is found to be free of wrinkles and under biaxial compressive strain.
The compressive strain in the epitaxial regions (0.25-0.40%) is higher than
regions where the graphene is not epitaxial with the underlying surface (0.20
0.25%). This orientation-dependent strain relaxation is through the loss of local
adhesion and the generation of graphene wrinkles. Density functional theory
calculations suggest a large frictional force between the epitaxial graphene and
the Cu(111) substrate, and this is therefore an energy barrier to the formation
of wrinkles in the graphene. Enhanced chemical reactivity is found in epitaxial
graphene on Cu(111) foils as compared to graphene on polycrystalline Cu foils for
certain chemical reactions. A higher compressive strain possibly favors lowering
the formation energy and/or the energy gap between the initial and transition
states, either of which can lead to an increase in chemical reactivity.
PMID- 29337386
TI - Synthesis and X-Ray Crystallographic Characterisation of Frustum-Shaped Ligated
[Cu18 H16 (DPPE)6 ]2+ and [Cu16 H14 (DPPA)6 ]2+ Nanoclusters and Studies on Their
H2 Evolution Reactions.
AB - We report new structural motifs for Cu nanoclusters that conceptually represent
seed crystals for large face-centred cubic (FCC) crystal growth. Kinetically
controlled syntheses, high resolution mass spectrometry experiments for
determination of the dication formulae and crystallographic characterisation were
carried out for [Cu18 H16 (DPPE)6 ][BF4 ][Cl] (DPPE=bis(diphenylphosphino)ethane)
and [Cu16 H14 (DPPA)6 ][(BF4 )2 ] (DPPA=bis(diphenylphosphino)amine) polyhydrido
nanoclusters, which feature the unprecedented bifrustum and frustum metal-core
architecture in metal nanoclusters. The Cu18 nanocluster contains two Cu9 frustum
cupolae and the Cu16 nanocluster has one Cu9 frustum cupola and a Cu7 distorted
hexagonal-shape base. Gas-phase experiments revealed that both Cu18 H16 and Cu16
H14 cores can spontaneously release H2 upon removal of one bisphosphine capping
ligand.
PMID- 29337388
TI - Reactions of an Aluminium/Phosphorus Frustrated Lewis Pair (FLP) with alpha,beta
Unsaturated Carbonyl Compounds: FLPs as Efficient Two-Electron Reductants with
the Formation of Enolates, a cis-Enediolate, and an Allene.
AB - The Al/P-based frustrated Lewis pair (FLP) Mes2 P-C(AltBu)2 =C(H)Ph (1;
Mes=mesityl) reacted as an efficient two-electron reductant with benzil to afford
a cis-enediolate that was coordinated to the FLP through P-O and Al-O bonds and
the formation of a seven-membered heterocycle (2). The phosphorus atom is
oxidised from +III to +V. Similar heterocycles (3 a to 3 f) were formed if 1 was
treated with various enones (acrolein, acrylate, acrylamide). The resulting
enolates are bound to the FLP through P-C and Al-O bonds. Cyclopropenone gave an
adduct (4) with the C=O bond coordinated by P and Al. Ynones gave a fascinating
variety of different structures. 1,3-Diphenylprop-2-yn-1-one afforded a
remarkable allene-type moiety with two cumulated C=C bonds (5); 3-hexyn-2-one
yielded a ligand with two conjugated C=C bonds by C-H bond activation at the
carbonyl methyl group (7); and 4-(trimethylsilyl)-3-butyn-2-one reacted by C-H
bond cleavage, formation of an enolate group with a terminal C=C bond, and shift
of the proton to the P atom (8). The C=C bond was not affected. Allene compound 5
rearranged at elevated temperature and in daylight through the formation of a
tricyclic compound by C-H bond activation and C-C bond formation. DFT
calculations on this unusual rearrangement suggest insertion of the central
allene C atom into the C-H bond of a methyl group and the intermediate formation
of a C3 ring.
PMID- 29337387
TI - Systematic review of predictive risk models for adverse drug events in
hospitalized patients.
AB - AIM: An emerging approach to reducing hospital adverse drug events is the use of
predictive risk scores. The aim of this systematic review was to critically
appraise models developed for predicting adverse drug event risk in inpatients.
METHODS: Embase, PubMed, CINAHL and Scopus databases were used to identify
studies of predictive risk models for hospitalized adult inpatients. Studies had
to have used multivariable logistic regression for model development, resulting
in a score or rule with two or more variables, to predict the likelihood of
inpatient adverse drug events. The Checklist for the critical Appraisal and data
extraction for systematic Reviews of prediction Modelling Studies (CHARMS) was
used to critically appraise eligible studies. RESULTS: Eleven studies met the
inclusion criteria and were included in the review. Ten described the development
of a new model, whilst one study revalidated and updated an existing score.
Studies used different definitions for outcome but were synonymous with or
closely related to adverse drug events. Four studies undertook external
validation, five internally validated and two studies did not validate their
model. No studies evaluated impact of risk scores on patient outcomes.
CONCLUSION: Adverse drug event risk prediction is a complex endeavour but could
help to improve patient safety and hospital resource management. Studies in this
review had some limitations in their methods for model development, reporting and
validation. Two studies, the BADRI and Trivalle's risk scores, used better model
development and validation methods and reported reasonable performance, and so
could be considered for further research.
PMID- 29337389
TI - Thiazole Imide-Based All-Acceptor Homopolymer: Achieving High-Performance
Unipolar Electron Transport in Organic Thin-Film Transistors.
AB - High-performance unipolar n-type polymer semiconductors are critical for
advancing the field of organic electronics, which relies on the design and
synthesis of new electron-deficient building blocks with good solubilizing
capability, favorable geometry, and optimized electrical properties. Herein, two
novel imide-functionalized thiazoles, 5,5'-bithiazole-4,4'-dicarboxyimide (BTzI)
and 2,2'-bithiazolothienyl-4,4',10,10'-tetracarboxydiimide (DTzTI), are
successfully synthesized. Single crystal analysis and physicochemical study
reveal that DTzTI is an excellent building block for constructing all-acceptor
homopolymers, and the resulting polymer poly(2,2'-bithiazolothienyl-4,4',10,10'
tetracarboxydiimide) (PDTzTI) exhibits unipolar n-type transport with a
remarkable electron mobility (MUe ) of 1.61 cm2 V-1 s-1 , low off-currents (Ioff
) of 10-10 -10-11 A, and substantial current on/off ratios (Ion /Ioff ) of 107
108 in organic thin-film transistors. The all-acceptor homopolymer shows
distinctive advantages over prevailing n-type donor-acceptor copolymers, which
suffer from ambipolar transport with high Ioff s > 10-8 A and small Ion /Ioff s <
105 . The results demonstrate that the all-acceptor approach is superior to the
donor-acceptor one, which results in unipolar electron transport with more ideal
transistor performance characteristics.
PMID- 29337390
TI - Salt-dependent aquagenic urticaria in children: Report of two cases.
PMID- 29337392
TI - Oral health-related concerns, behavior, and communication with health care
providers of patients with breast cancer: impact of different treatments.
AB - AIM: The objectives are to compare responses of breast cancer (BCa) treatment
groups (chemotherapy, tamoxifen, and aromatase inhibitors (AIs) to each other and
a control regarding (a) subjective oral health, (b) oral health-related
behaviors, (c) oral health-related concerns, and (d) communication with health
care providers. METHODS: Survey data were collected from 140 postmenopausal BCa
patients and 41 healthy postmenopausal control respondents. RESULTS: BCa patients
reported on average more frequent mouth sores/mucositis (5-point scale with 1 =
never: 1.63 vs. 1.14; p < .01), glossadynia (1.60 vs. 1.07; p < .01), xerostomia
(2.48 vs. 1.40; p < .01), and dysgeusia (2.10 vs. 1.46; p < .01) than the control
respondents. Patients undergoing chemotherapy were more aware that cancer
treatment can affect their oral health than patients on tamoxifen/AI (93% vs.
55%/56%; p < .001). BCa patients reported being more frequently informed by
oncologists about oral health-related effects of cancer treatment than by
dentists. Oncologists/nurses were more likely to communicate about oral health
related treatment effects with patients undergoing chemotherapy than patients on
tamoxifen or AIs. Few BCa patients perceived dentists as knowledgeable about
cancer treatment-related oral concerns and trusted them less than oncologists.
CONCLUSIONS: BCa treatments impact oral health. Low percentages of BCa patients
had received specific information about impacts of BCa treatments on oral health
from their dentists.
PMID- 29337391
TI - Time-dependent distinct roles of Toll-like receptor 4 in a house dust mite
induced asthma mouse model.
AB - House dust mites (HDMs) are a common source of allergens that trigger both
allergen-specific and innate immune responses in humans. Here, we examined the
effect of allergen concentration and the involvement of Toll-like receptor 4
(TLR4) in the process of sensitization to house dust mite allergens in an HDM
extract-induced asthma mouse model. Intranasal administration of HDM extract
induced an immunoglobulin E response and eosinophilic inflammation in a dose
dependent manner from 2.5 to 30 MUg/dose. In TLR4-knockout mice, the infiltration
of eosinophils and neutrophils into the lung was decreased compared with that in
wild-type mice in the early phase of inflammation (total of three doses).
However, in the late phase of inflammation (total of seven doses), eosinophil
infiltration was significantly greater in TLR4-knockout mice than in wild-type
mice. This suggests that the roles of TLR4 signaling are different between the
early phase and the later phase of HDM allergen-induced inflammation. Thus,
innate immune response through TLR4 regulated the response to HDM allergens, and
the regulation was altered during the phase of inflammation.
PMID- 29337393
TI - Provision of information on dental implant treatment: Patients' thoughts and
experiences.
AB - OBJECTIVES: To explore patients' thoughts and perceptions of information
provision regarding dental implant treatment. METHODS: This generic qualitative
study involved 38 semi-structured face-to-face and telephone interviews with 34
participants, who were at different stages of dental implant treatment. The
interviews were transcribed verbatim. The data collection and coding process
followed the principles of qualitative thematic analysis. RESULTS: Clinical
sources of information were generally trusted by patients; however, patients
clearly lacked information relative to their own specific situation, concerns and
preferences, and this may lead to patients' reliance on other general sources of
information. Crucial information on the long-term prosthesis needs was requested
by patients at all treatment stages. Issues concerning the longevity and
functional capability of the implant restoration and the long-term maintenance
including optimisation of hygiene practice were questioned by patients and
required greater explanation. CONCLUSION: With growing patient interest in
implants for replacement of missing teeth, complete and accurate knowledge and
understanding of implants should be established with patients. This should be
undertaken with more reliance on reliable clinically based sources of implant
information.
PMID- 29337394
TI - 3D Printing of Materials with Tunable Failure via Bioinspired Mechanical
Gradients.
AB - Mechanical gradients are useful to reduce strain mismatches in heterogeneous
materials and thus prevent premature failure of devices in a wide range of
applications. While complex graded designs are a hallmark of biological
materials, gradients in manmade materials are often limited to 1D profiles due to
the lack of adequate fabrication tools. Here, a multimaterial 3D-printing
platform is developed to fabricate elastomer gradients spanning three orders of
magnitude in elastic modulus and used to investigate the role of various
bioinspired gradient designs on the local and global mechanical behavior of
synthetic materials. The digital image correlation data and finite element
modeling indicate that gradients can be effectively used to manipulate the stress
state and thus circumvent the weakening effect of defect-rich interfaces or
program the failure behavior of heterogeneous materials. Implementing this
concept in materials with bioinspired designs can potentially lead to defect
tolerant structures and to materials whose tunable failure facilitates repair of
biomedical implants, stretchable electronics, or soft robotics.
PMID- 29337395
TI - Testosterone Suppression with Luteinizing Hormone-Releasing Hormone (LHRH)
Agonists in Patients Receiving Radiotherapy for Prostate Cancer.
AB - OBJECTIVES: To characterize the probability of testosterone escape during a
course of radiotherapy and androgen deprivation (ADT) in patients with prostate
cancer, and examine predictors of testosterone escape, the prostate specific
antigen (PSA) levels during testosterone escape, and the impact of testosterone
escape on outcome. PATIENTS AND METHODS: To participate in the database review,
necessary data included: (i) type of luteinizing hormone-releasing hormone
agonist (LHRHa) administered, date of initiation, and date of cessation or
duration of therapy, (ii) radiotherapy information (start date and dose) with at
least 6 months of follow-up after radiotherapy, (iii) radiotherapy to the
prostate or prostate bed, and (iv) at least one serum testosterone and PSA
measurement. RESULTS: Five hundred sixty patients in the database were identified
as being treated with radiotherapy and ADT. Three hundred seventy-five patients
had at least one measurement of testosterone and PSA, and the type of LHRHa used
could be determined in 361 patients. Median follow-up of patients still living
was 4.7 years. The median number of testosterone measurements per patient was
six. The incidence of testosterone escape per patient course of treatment was
buserelin, 9.3%; goserelin, 10.5%; intramuscular leuprolide, 11.5%; leuprolide
subcutaneous, 23.9%; and triptorelin, 6.7% (p = 0.02). There was no difference in
either biochemical failure-free survival or overall survival in patients
stratified by testosterone escape. The modal PSA level during a testosterone
escape was an undetectable PSA. CONCLUSIONS: An undetectable PSA does not rule
out the presence of higher than desired levels of testosterone during ADT. In
this cohort of patients, there appears to be no impact of testosterone escape on
either biochemical relapse-free survival or overall survival.
PMID- 29337396
TI - Aging and hypertension decrease endothelial NO-related dilating function and
gamma-glutamyl transferase activity but not S-nitrosoglutathione-induced aortic
vasodilation.
AB - S-nitrosoglutathione (GSNO), which is involved in the transport and the storage
of NO, induces vasorelaxation. It requires gamma-glutamyl transferase (GGT), an
enzyme present on the endothelium, to transfer NO into the cell. We evaluated
whether aging and hypertension, which induce NO-related dilating dysfunction, are
associated with decreased vascular GGT activity and modify the vasorelaxant
effect of GSNO. Thoracic aortic rings isolated from male spontaneous hypertensive
rats (SHR) and Wistar-Kyoto rats (WKY) aged 20-22 (adult) or 57-60 weeks (mature)
were preconstricted with phenylephrine, then submitted to concentration
vasorelaxant response curves (maximal response: Emax ; pD2 ) to GSNO and
carbachol (the latter to measure NO-related dilating function). GGT activity was
measured using chromogenic substrate. Both aging and hypertension lowered Emax
values for carbachol (Emax -8% in adult SHR, -42% in mature SHR vs. age-matched
WKY, page and phypertension < 0.05) demonstrating NO-related dilating
dysfunction. Aortic GGT activity also decreased with aging and hypertension (-22%
in adult and -75%, reaching 3 nmol/min/g of tissue, in mature SHR vs. 12 in age
matched WKY and 23 in adult WKY, page and phypertension < 0.05). The pD2 values
of GSNO were similar in mature SHR and WKY but higher in adult SHR (pinteraction
< 0.05). Aging in hypertensive rats decreased NO-related vasorelaxant function
and vascular GGT activity, but did not lower the vasorelaxant response to GSNO.
This opens perspectives for GSNO-based therapeutics restoring nitric oxide
bioavailability and vascular protection in a context of endothelial dysfunction.
PMID- 29337397
TI - 2D PdAg Alloy Nanodendrites for Enhanced Ethanol Electroxidation.
AB - The development of highly active and stable electrocatalysts for ethanol
electroxidation is of decisive importance to the successful commercialization of
direct ethanol fuel cells. Despite great efforts invested over the past decade,
their progress has been notably slower than expected. In this work, the facile
solution synthesis of 2D PdAg alloy nanodendrites as a high-performance
electrocatalyst is reported for ethanol electroxidation. The reaction is carried
out via the coreduction of Pd and Ag precursors in aqueous solution with the
presence of octadecyltrimethylammonium chloride as the structural directing
agent. Final products feature small thickness (5-7 nm) and random in-plane
branching with enlarged surface areas and abundant undercoordinated sites. They
exhibit enhanced electrocatalytic activity (large specific current ~2600 mA mgPd
1) and excellent operation stability (as revealed from both the cycling and
chronoamperometric tests) for ethanol electroxidation. Control experiments show
that the improvement comes from the combined electronic and structural effects.
PMID- 29337398
TI - Exploring knowledge, attitudes and experience of genitourinary symptoms in women
with early breast cancer on adjuvant endocrine therapy.
AB - Clinical trials of adjuvant endocrine therapy in women with early breast cancer
have consistently reported that genitourinary symptoms are common. However,
little is known about women's experiences of genitourinary symptoms, their views
about the symptoms and how they impact on their lives. The aim of this study was
to explore knowledge, attitudes and experiences of genitourinary symptoms among
women receiving adjuvant endocrine therapy for early breast cancer. Thirty-two
semi-structured interviews were conducted and subjected to a rigorous qualitative
analysis. Genitourinary symptoms were commonly reported to negatively impact on
personal, social and physical activities, were often attributed to anxiety and
stress and were a source of embarrassment. Women also commented on the limited
information available or provided regarding the potential genitourinary adverse
effects of adjuvant endocrine therapy. There was a general lack of awareness that
their symptoms could be associated with or exacerbated by adjuvant endocrine
therapy. Women indicated a preference to receive information and advice about
potential management options from either their general practitioner or
specialist. These findings underscore the importance of improving communication
and increasing awareness among both clinicians and patients about the potential
impact of adjuvant endocrine therapy on genitourinary symptoms.
PMID- 29337399
TI - Impact of pregnancy on psychoactive substance use among women with substance use
disorders recruited in addiction specialized care centers in France.
AB - Pregnancy can be a motivation for decrease in drug abusing but may also represent
a period of high vulnerability for relapse. We aimed to assess psychoactive
substance use among women with substance use disorders followed in addiction care
centers in France. We analyzed data from women aged 15-44 years included in the
'Observation of illegal drugs and misuse of psychotropic medication (OPPIDUM)
survey', an annual cross-sectional survey collecting details on psychoactive
substances used. Characteristics of women included in 2005-2012 yearly surveys
were compared depending on their pregnant or not pregnant status. Factors,
including pregnancy, associated with illicit substance use and medication misuse
were investigated through logistic regression. The study included 518 pregnant
and 6345 nonpregnant women; 85.3% pregnant women were on opioid maintenance
therapy (OMT) (vs. 77.1% of nonpregnant). Pregnancy was associated with lower
illicit substance use (adjusted OR 0.71 [0.58-0.88]) and with lower medication
misuse (0.66 [0.49-0.89]), whereas financial insecurity and living as a couple
were associated with increased risk. Raising children was significantly
associated with less risk of substance use. Each substance taken separately, the
part of women using illicit substance or misusing medication did not differ
depending on whether they were pregnant or not, except for heroin (24.5% in
pregnant vs. 17.9% nonpregnant; <0.001). This nationwide study provides new
insights into psychoactive substance use in a large mixed population of women
with drug use disorders. Results outline the challenge of preventing drug use and
initiating care strategies with a specific approach on socio-economic
environment.
PMID- 29337400
TI - Immunization in end stage renal disease: The perception of waiting list patients.
AB - BACKGROUND: The number of patients with chronic kidney disease is increasing
worldwide, as well as the number of patients in kidney transplant waiting lists.
In order to prevent infections related to immunosuppressive therapy, immunization
guidelines for CKD patients before transplantation have been proposed. The aim of
the present study was to evaluate adherence to immunization in a cohort of CKD
patients in transplant waiting list and their renal replacement therapy clinics.
METHODS: CKD patients older than 18 years old, receiving renal replacement
therapy longer than 12 months and included in kidney transplant waiting list at
University of Campinas (Unicamp) were enrolled. RESULTS: From February 2014 to
December 2015, 105 patients fulfilled the inclusion criteria. Complete hepatitis
B vaccination was observed in 73% and influenza vaccine in 67%. None of the other
vaccine protocols reached 50% of coverage. Patients receiving immunization at
primary health units presented higher coverage for diphtheria, tetanus (dT),
measles, mumps, rubella (MMR), and hepatitis B vaccines, while patients immunized
at renal replacement therapy clinics showed higher prevalence of pneumococcus
(pneumo23). CONCLUSION: The low rates of immunization could reflect the RRT's
clinics knowledge about the vaccines guidelines and its application on daily
care. We suggest an integration between transplant center and RRT clinics,
through lectures, periodic checking of vaccination cards, and easy to follow
guidelines in order to provide a better vaccine coverage and to obtain higher
immunization rates.
PMID- 29337402
TI - Effect of length of dental resident clinical rotations on patient behavior.
AB - AIM: The purpose of this retrospective chart review study was to determine if the
length of residents' comprehensive dental care rotations in a general practice
residency affected late cancellations, broken appointments, completion of
treatment, timeliness of recall visits, emergency visits, and the need for redo
of restorations and prostheses. METHODS: Patients who presented for comprehensive
care from 2010 to 2013, during which residents had 3- to 4-month dental clinic
rotations, comprised Group 1, and patients who presented for comprehensive care
from 2013 to 2016, during which residents had 11-month dental clinic rotations,
comprised Group 2. Subjects were excluded if they only presented for emergency
care, they had only one visit, or their care was delivered in both time periods.
There were 105 patients in Group 1 and 55 patients in Group 2. RESULTS: The
statistically significant results were that Group 1 patients had more late
cancellations and broken appointments and failed to reach recall status more
often than Group 2 patients, and that Group 1 patients had fewer emergency
visits. CONCLUSION: Within the limitations of this retrospective study, the
results suggest that short block rotations have an adverse effect on resident
experience and outcomes of patient care in a hospital outpatient setting.
PMID- 29337401
TI - Rhabdomyolysis after co-administration of a statin and fusidic acid: an analysis
of the literature and of the WHO database of adverse drug reactions.
AB - Following a severe case of rhabdomyolysis in our University Hospital after a co
administration of atorvastatin and fusidic acid, we describe this interaction as
this combination is not clearly contraindicated in some countries, particularly
for long-term treatment by fusidic acid. All cases of rhabdomyolysis during a co
administration of a statin and fusidic acid were identified in the literature and
in the World and Health Organization database, VigiBase(r) . In the literature,
29 cases of rhabdomyolysis were identified; mean age was 66 years, median
duration of co-administration before rhabdomyolysis occurrence was 21 days, 28%
of cases were fatal. In the VigiBase(r) , 182 cases were retrieved; mean age was
68 years, median duration of co-administration before rhabdomyolysis was 31 days
and 24% of cases were fatal. Owing to the high fatality associated with this co
administration and the long duration of treatment before rhabdomyolysis
occurrence, fusidic acid should be used if there is no appropriate alternative,
as long as statin therapy is interrupted for the duration of fusidic acid
therapy, and perhaps a week longer. Rarely will interruption of this sort have
adverse consequences for the patient.
PMID- 29337404
TI - Mass trapping designs for organic control of the Japanese beetle, Popillia
japonica (Coleoptera: Scarabaeidae).
AB - BACKGROUND: In some regions of North America, damage caused by the Japanese
beetle, Popillia japonica, has been increasing as beetle populations continue to
become established and expand. This poses a pest management challenge for crop
farmers, in particular organic producers. From 2014 to 2016 we evaluated the
ability of novel mass trapping systems to capture P. japonica in elderberry and
blueberry orchards in Missouri, USA. RESULTS: Across a 3-year period in two
locations, the mass trapping systems collected 10.3 million P. japonica adults
while season-long adult densities on crop plants were comparatively low
(elderberry: 0.5-3.7 per plant; blueberry: 0.01-0.07 per plant). Damage by P.
japonica averaged 6.8% per plant in elderberry and 0.12% in blueberry. In 2015
and 2016, large-capacity bins with increased ventilation captured similar beetle
numbers as did 1.2-m-long mesh socks (single design used in 2014), and these two
trap designs outperformed non-ventilated bins. CONCLUSION: The mass trapping
designs captured high numbers of adult P. japonica, while comparatively few
adults and little damage to the foliage were recorded on plants. Mass trapping
may provide effective alternative management options for P. japonica with less or
no insecticides applied to the crop. (c) 2018 Society of Chemical Industry.
PMID- 29337405
TI - Effects of transcutaneous electrical nerve stimulation on pain intensity during
application of carboxytherapy in patients with cellulite: A randomized placebo
controlled trial.
AB - BACKGROUND: Carboxytherapy may generate local pain that is considered the main
limiting factor in clinical practice. Transcutaneous electric nerve stimulation
(TENS) is widely used in the control of acute pain; however, the effect of TENS
on pain relief during carboxytherapy has not been studied to date. AIMS: To
assess the effect of TENS on pain intensity during carboxytherapy in patients
with cellulite in the gluteal region. PATIENTS/METHODS: This randomized clinical
trial was conducted with 84 patients, 18-44 years of age, who had moderate
cellulite in the gluteal region, according to Cellulite Severity Scale, but never
received carboxytherapy. Patients were randomized into 3 groups: active TENS,
placebo TENS, and control group. For the intervention, skin depressions with
cellulite were outlined, and the gluteal area to be treated was defined. The
subcutaneous injection of CO2 was performed using 0.30 * 13 mm-needles at a 45
degrees angle, with a controlled flow rate of 100 mL/min maintained for 1 minute
at each puncture site. The parameters for TENS were as follows: frequency of 100
Hz and pulse duration of 200 MUs; TENS intensity was adjusted until the patient
reported strong paresthesia. The visual numeric pain rating scale was used to
assess pain intensity after each puncture. RESULTS: The active TENS group
reported lower pain intensity compared to the placebo TENS (P < .0001) and
control (P < .0001) groups. CONCLUSIONS: Transcutaneous electric nerve
stimulation (TENS) was effective in reducing pain intensity during carboxytherapy
in patients with cellulite in the gluteal region.
PMID- 29337406
TI - Validation of flow cytometric analysis of platelet function in patients with a
suspected platelet function defect.
AB - : Essentials The diagnosis of mild platelet function disorders (PFDs) is
challenging. Validation of flow cytometric testing in patients with suspected
PFDs is required. Flow cytometry has added value to light transmission
aggregometry (LTA) in diagnosis of PFDs. There is fair agreement in diagnosing
PFDs between LTA and flow cytometry. SUMMARY: Background Light transmission
aggregometry (LTA) is the most commonly used test for the diagnosis of platelet
function disorders (PFDs), but has moderate sensitivity for mild PFDs. Flow
cytometry has been recommended for additional diagnostics of PFDs but is not yet
standardized as a diagnostic test. We developed a standardized protocol for flow
cytometric analysis of platelet function that measures fibrinogen binding and P
selectin expression as platelet activation markers in response to agonist
stimulation. Objectives To determine the additional value of flow cytometric
platelet function testing to standard LTA screening in a cross-sectional cohort
of patients with a suspected PFD. Methods Platelet function was assessed with
flow cytometry and LTA in 107 patients suspected of a PFD in whom von Willebrand
disease and coagulation factor deficiencies were excluded. Both tests were
compared in terms of agreement and discriminative ability for diagnosing patients
with PFDs. Results Out of 107 patients, 51 patients had an elevated bleeding
score; 62.7% of the patients had abnormal platelet function measured with flow
cytometry and 54.2% of the patients were abnormal based on LTA. There was fair
agreement between LTA and flow cytometry (kappa = 0.32). The discriminative
ability of flow cytometric analysis in patients with an elevated bleeding score
was good (AUC 0.82, 0.74-0.90), but moderate for LTA (AUC 0.70, 0.60-0.80). Both
tests combined had a better discriminative ability (AUC 0.87, 0.80-0.94).
Conclusion Flow cytometric analysis of platelet function has added value in
diagnostics of PFDs in patients with unexplained bleeding tendency.
PMID- 29337407
TI - Insufficient sleep syndrome: An unrecognized but important clinical entity.
AB - BACKGROUND: A sleep clinic for adults and children was established in the Tokyo
Bay Urayasu Ichikawa Medical Centre, in August 2012. Given that few sleep clinics
are available in Japan specifically for children, this clinic provides the
opportunity to provide data on child patients with sleep problems. METHODS:
Records of patients who visited the sleep clinic at the Tokyo Bay Urayasu
Ichikawa Medical Centre aged <=20 years at the first visit were retrospectively
examined, along with the initial and final diagnoses. RESULTS: Of 2,157 patients
who visited the sleep clinic at Tokyo Bay Urayasu Ichikawa Medical Centre between
August 2012 and March 2017, 181 were <=20 years old. In these 181 patients, the
most frequent final diagnosis was insufficient sleep syndrome (ISS), n = 56,
followed by circadian rhythm sleep-wake disorder, n = 28; insomnia, n = 28; and
sleep-related movement disorder, n = 15. CONCLUSIONS: Insufficient sleep produces
various brain dysfunctions in both adults and children, and is associated with
behavioral, cognitive and physical problems, as well as with atypical early
development. Insufficient sleep has also been reported to cause obesity.
Insufficient sleep-induced obesity is often associated with the occurrence of
metabolic syndrome. More effort is needed to ensure that children are receiving
sufficient sleep.
PMID- 29337408
TI - Maternally expressed miR-379/miR-544 cluster is dispensable for testicular
development and spermatogenesis in mice.
PMID- 29337409
TI - Engineering of 'Purple Embryo Maize' with a multigene expression system derived
from a bidirectional promoter and self-cleaving 2A peptides.
PMID- 29337410
TI - Transcriptomic insight into pathogenicity-associated factors of Conidiobolus
obscurus, an obligate aphid-pathogenic fungus belonging to Entomopthoromycota.
AB - BACKGROUND: Conidiobolus obscurus is a widespread fungal entomopathogen with
aphid biocontrol potential. This study focused on a de novo transcriptomic
analysis of C. obscurus. RESULTS: A number of pathogenicity-associated factors
were annotated for the first time from the assembled 17 231 fungal unigenes,
including those encoding subtilisin-like proteolytic enzymes (Pr1s), trypsin-like
proteases, metalloproteases, carboxypeptidases and endochitinases. Many of these
genes were transcriptionally up-regulated by at least twofold in mycotized
cadavers compared with the in vitro fungal cultures. The resultant transcriptomic
database was validated by the transcript levels of three selected pathogenicity
related genes quantified from different in vivo and in vitro material in real
time quantitative polymerase chain reaction (PCR). The involvement of multiple
Pr1 proteases in the first stage of fungal infection was also suggested.
Interestingly, a unique cytolytic (Cyt)-like delta-endotoxin gene was highly
expressed in both mycotized cadavers and fungal cultures, and was more or less
distinct from its homologues in bacteria and other fungi. CONCLUSION: Our
findings provide the first global insight into various pathogenicity-related
genes in this obligate aphid pathogen and may help to develop novel biocontrol
strategy against aphid pests. (c) 2018 Society of Chemical Industry.
PMID- 29337411
TI - The Fourth Wave of Biocatalysis Emerges- The 13 th International Symposium on
Biocatalysis and Biotransformations.
AB - Ride the wave! Biocatalysis uses nature's catalysts, enzymes and whole cell
systems, for synthetic purposes. In a biotransformation, the biocatalyst
transforms a well-defined substrate to the desired product, in contrast to the
fermentation process, which produces the desired product from a complex mixture
of nutrients. Biocatalysis has reached an industrially established level through
several waves of technological evolution; participants of the BioTrans 2017
conference in Budapest could witness the newest wave of this technology.
PMID- 29337412
TI - Metallic Nanodot Patterns with Unique Symmetries Templated from ABC Triblock
Terpolymer Networks.
AB - Nanotemplates derived from the self-assembly of AB-type block copolymers provide
an elegant route to achieve well-defined metallic dot arrays, even if the variety
of pattern symmetries is restricted due to the limited number of structures
offered by microphase separated diblock copolymers. A strategy that relies on the
use of complex network structures accessible through the self-assembly of linear
ABC-type terpolymers is presented for the formation of metallic nanodots arrays
with "outside-the-box" symmetries. Patterned templates formed by the cubic Q214
and orthorhombic O70 network structures are used as excellent platforms to build
well-ordered gold nanodot arrays with unique p3m1 and p2 symmetries,
respectively. A simple yet efficient blending strategy is used to tune the
critical dimensions of the p3m1 pattern while laterally ordered gold nanodot
arrays are also demonstrated through a directed self-assembly approach. Such
highly ordered gold nanodots with tunable particle dimensions and array periods,
enabling the control of their plasmonic responses, are attractive probes for
biological imaging.
PMID- 29337413
TI - Participation of relatives in the care of cancer patients in hospital-A scoping
review.
AB - The purpose of the review was to describe what kind of research has been
conducted concerning relatives' participation in the care of cancer patients in
hospital and how relatives have participated in the care. Data (n = 9) were
identified through a manual search and by searching the electronic databases (n =
8) Cinahl, PubMed and Cochrane Library and analysed with deductive content
analysis. According to the review, participation in the concrete care appeared as
taking care of comprehensive care and the quality of care, helping with daily
activities and helping the healthcare professionals. Emotional support appeared
as protecting, supporting and visiting the patient and discussing with the
patient. Participation in decision-making appeared as acting as an advocate for
the patient, participating in the discussion concerning the decision-making and
participating in the discussion concerning the decisions of end of life.
According to the review, research concerning this topic seems to be rare. While
hospital periods are shortening and homecare is increasing, the role of relatives
as a supporter of the cancer patient is becoming even stronger. In the future,
more research should be conducted how the patients experience participation and
what are their wishes.
PMID- 29337414
TI - Proliferative leukoplakia: Proposed new clinical diagnostic criteria.
AB - OBJECTIVE: We aimed to characterize proliferative verrucous leukoplakia (PVL)
from a clinical and histopathological standpoint and suggest an updated
classification. SUBJECTS AND METHODS: Records of patients seen at three oral
medicine centers with a clinical diagnosis of PVL were reviewed for clinical and
histopathological features and malignant transformation (MT). RESULTS: There were
42 patients (median age: 69 years [range: 36-88]; 35 females). 12.2% were current
smokers. Family history of cancer was present in 43.7% of patients. Partial
demarcation of lesion margins was present in 31.3% of lesions, followed by
verrucous (27.5%), smooth (22.7%) erythematous (22.3%), and fissured (18.3%)
appearance. Large and contiguous and multisite and non-contiguous lesions
comprised 57.1% (24/42) and 35.7% (15/42) of PVL cases, respectively. 19.1% had
prominent erythema (erythroleukoplakia). The most common histopathological
diagnosis at first visit was hyperkeratosis without dysplasia (22/42; 56.4%). MT
occurred in 71.4% patients after a median of 37 months [range: 1-210] from
initial visit; erythroleukoplakia exhibited MT in 100% of cases. CONCLUSION: The
generic term "proliferative leukoplakia (PL)" may be more appropriate than PVL
because 18.3% were fissured and 22.7% erythematous. We also propose the term
proliferative erythroleukoplakia to more accurately describe the subset of PL
with prominent erythema, which had the highest MT rate.
PMID- 29337415
TI - Self-Healing in Supramolecular Polymers.
AB - Adaption and self-healing are two major principles in material science, often
coupled with the placement of supramolecular moieties within a material. Proper
molecular design can enable self-healing within such materials, displaying
enormous potential in technology and application. Here, basic physicochemical
aspects as well as new material developments in the field are described,
published after a recent review in Macromolecular Rapid Communications in 2013.
PMID- 29337416
TI - The role of ADAMTS-13 in the coagulopathy of sepsis.
AB - The interaction between platelets and the vessel wall is mediated by various
receptors and adhesive proteins, of which von Willebrand factor (VWF) is the most
prominent. The multimeric size of VWF is an important determinant of a more
intense platelet-vessel wall interaction, and is regulated by the VWF-cleaving
protease ADAMTS-13. A deficiency in ADAMTS-13 leads to higher concentrations of
ultralarge VWF multimers and pathological platelet-vessel wall interactions, in
its most typical and extreme form leading to thrombocytopenic thrombotic purpura,
a thrombotic microangiopathy characterized by thrombocytopenia, non-immune
hemolysis, and organ dysfunction. Thrombotic microangiopathy associated with low
levels of ADAMTS-13 may be a component of the coagulopathy observed in patients
with sepsis. Here, we review the potential role of ADAMTS-13 deficiency and
ultralarge VWF multimers in sepsis, and their relationship with sepsis severity
and prognosis. In addition, we discuss the possible benefit of restoring ADAMTS
13 levels or reducing the effect of ultralarge VWF as an adjunctive treatment in
patients with sepsis.
PMID- 29337417
TI - Guillain-Barre syndrome in a local area in Japan, 2006-2015: an epidemiological
and clinical study of 108 patients.
AB - BACKGROUND AND PURPOSE: Many epidemiological studies of Guillain-Barre syndrome
(GBS) and Fisher syndrome (FS) have been conducted in Europe and America. In
contrast, epidemiological studies are rare in Asia where the GBS subtypes differ
from those in Western countries. This study was undertaken to clarify the
incidence of GBS and FS in a local area in Japan as well as their seasonal
trends. METHOD: Seventy-one GBS and 37 FS patients were recorded from 2006 to
2015 in an area of approximately 1.5 million inhabitants in Japan. The incidence,
seasonal trends and clinical features of GBS and FS were examined. RESULTS: The
incidence rate of GBS was 0.42 cases per 100 000 person-years and that of FS was
0.22 cases per 100 000 person-years. The incidence of GBS increased with age and
FS affected predominantly patients aged from 45 to 64 years old. There was some
seasonal clustering of acute motor axonal neuropathy (AMAN) and FS in spring and
summer, but it was not significant. AMAN and FS patients had a high frequency of
preceding infection (AMAN, 68% gastrointestinal infection; FS, 65% upper
respiratory infection). Antecedent respiratory infection was significantly
associated with FS as an outcome. Serum antibodies to ganglioside GM1 were
detected in 71% of AMAN patients and antibodies to GQ1b were detected in 81% of
FS patients. CONCLUSIONS: Our study offers evidence of a lower incidence of GBS
and a higher incidence of FS in a local area in Japan than in Western countries.
PMID- 29337418
TI - Specific Noncovalent Interactions Determine Optimal Structure of a Buried Ligand
Moiety: QM/MM and Pure QM Modeling of Complexes of the Small-Molecule CD4
Mimetics and HIV-1 gp120.
AB - The small-molecule CD4 mimetics (smCD4mcs) are a class of highly potent HIV-1
entry inhibitors characterized by a unique structure-activity relationship (SAR).
They share a halogenated phenyl ring (region 1) that deeply inserts into an
otherwise water-filled cavity at the CD4 binding site on the gp120 surface, the
so-called F43 cavity. Conservative modifications to region 1 away from this
halogenated phenyl motif have all led to loss of activity, despite the fact that
they are predicted by standard empirical computational approaches to bind equally
well, making it difficult to further optimize this region of the compounds to
increase binding to gp120. In this study we used quantum mechanical methods to
understand the roots of the interactions between region 1 and the F43 cavity. We
clearly demonstrate the presence of halogen bond/sigma-hole and dispersion
interactions between region 1 and the F43 cavity residues F376-N377, which are
not captured by standard molecular mechanics approaches and the role played by
the smCD4mc in the F43 cavity desolvation. These findings rationalize why the
halogenated region 1 has proven so difficult to move beyond in smCD4mc
optimization, in agreement with experimental evidence.
PMID- 29337419
TI - Evolution of resistance to chytridiomycosis is associated with a robust early
immune response.
AB - Potentiating the evolution of immunity is a promising strategy for addressing
biodiversity diseases. Assisted selection for infection resistance may enable the
recovery and persistence of amphibians threatened by chytridiomycosis, a
devastating fungal skin disease threatening hundreds of species globally.
However, knowledge of the mechanisms involved in the natural evolution of
immunity to chytridiomycosis is limited. Understanding the mechanisms of such
resistance may help speed-assisted selection. Using a transcriptomics approach,
we examined gene expression responses of endangered alpine tree frogs (Litoria
verreauxii alpina) to subclinical infection, comparing two long-exposed
populations with a naive population. We performed a blinded, randomized and
controlled exposure experiment, collecting skin, liver and spleen tissues at 4, 8
and 14 days postexposure from 51 wild-caught captively reared infection-naive
adult frogs for transcriptome assembly and differential gene expression analyses.
We analysed our results in conjunction with infection intensity data, and the
results of a large clinical survival experiment run concurrently with individuals
from the same clutches. Here, we show that frogs from an evolutionarily long
exposed and phenotypically more resistant population of the highly susceptible
alpine tree frog demonstrate a more robust innate and adaptive immune response at
the critical early subclinical stage of infection when compared with two more
susceptible populations. These results are consistent with the occurrence of
evolution of resistance against chytridiomycosis, help to explain underlying
resistance mechanisms, and provide genes of potential interest and sequence data
for future research. We recommend further investigation of cell-mediated immunity
pathways, the role of interferons and mechanisms of lymphocyte suppression.
PMID- 29337420
TI - A proinflammatory response of bovine endometrial epithelial cells to active sperm
in vitro.
AB - In the cow, cryopreserved semen is inseminated into the uterus, and most of sperm
are removed by backflow and phagocytes. Nevertheless, the mechanism responsible
for sperm phagocytosis is unclear. Here, we used cultured bovine uterine
epithelial cells (BUECs) to investigate the uterine response to sperm and the
mechanism that activates polymorphonuclear neutrophils (PMNs). BUEC monolayers
were co-cultured with different numbers of washed sperm obtained from
cryopreserved semen (104 , 105 , and 106 sperm/ml) for 3 hr. Sperm dose
dependently up-regulated IL8 (Interleukin 8). Sperm at 106 /ml increased mRNA
expression of TNFA (Tumor necrosis factor alpha), IL1B (Interleukin 1B), NFKB2
(Nuclear factor kappa B2), and C3 (Complement factor 3), as well as PGES
(Prostaglandin E synthase) expression and PGE2 release. Live sperm, but not dead
sperm, attached to BUECs, and dead sperm did not induce an acute inflammatory
response. Time-dependent effects were evaluated by co-culture of 106 /ml washed
sperm with BUECs for 0, 1, 3, and 6 hr. The number of detached sperm increased
gradually toward 6 hr. Maximum mRNA expression of IL8, TNFA, IL1B, and NFKB2 was
induced at 3 hr, while C3 continued to increase toward 6 hr. Sperm did not
stimulate mRNA expression of anti-inflammatory cytokines TGFB1 (Transforming
growth factor beta 1) or IL10 (Interleukin 10). Medium conditioned by sperm co
incubated with BUECs stimulated PMNs phagocytosis of sperm in vitro. Fresh media
supplemented with low levels of IL1B, TNFA, and PGE2 up-regulated sperm
phagocytosis by PMNs as well. In conclusion, our findings strongly suggest that
the active sperm attach to BUECs and trigger uterine local innate immunity with
induction of a pro-inflammatory response that enhances sperm phagocytosis by
PMNs.
PMID- 29337421
TI - Fenoxaprop-P-ethyl resistance conferred by cytochrome P450s and target site
mutation in Alopecurus japonicus.
AB - BACKGROUND: Alopecurus japonicus is a serious grass weed species in wheat fields
in eastern Asia, and has evolved strong resistance to acetyl-CoA carboxylase
(ACCase)-inhibiting herbicides. Although target-site resistance (TSR) to ACCase
inhibitors in A. japonicus has been reported, non-target site resistance (NTSR)
has not. This study investigated both TSR and NTSR in a fenoxaprop-P-ethyl
resistant A. japonicus population (AHFD-3), which was collected in Feidong
County, Anhui Province, China. RESULTS: We found that AHFD-3 exhibited high
resistance to fenoxaprop-P-ethyl and low resistance to flucarbazone-sodium. The
sensitivity of AHFD-3 to fenoxaprop-P-ethyl increased significantly after
treatment with cytochrome P450 (P450) inhibitors; however, such synergies between
P450 inhibitors and fenoxaprop-P-ethyl were not found in two control populations.
Sequences of the entire carboxyltransferase domain of A. japonicus ACCase were
obtained, and AHFD-3 plants showed an Asp-2078-Gly substitution in the ACCase.
With the derived cleaved amplified polymorphic sequence (dCAPS) method, we found
that 85.4% of the plants of AHFD-3 carried this mutation. The P450 content in
AHFD-3 plants was significantly higher than those of the two control populations
after treatment with fenoxaprop-P-ethyl. Ten partial sequences of P450 genes in
A. japonicus were cloned. Three P450 genes were up-regulated 12 h after
fenoxaprop-P-ethyl treatment, which were all from the P450 subfamily CYP72A.
Moreover, a P450 gene from the P450 family CYP81 was up-regulated after
fenoxaprop-P-ethyl treatment in all populations studied. CONCLUSION: Fenoxaprop-P
ethyl resistance in AHFD-3 plants was conferred by up-regulation of cytochrome
P450s in the CYP72A subfamily and target site mutation of the ACCase gene. (c)
2018 Society of Chemical Industry.
PMID- 29337422
TI - Hollow Mesoporous Silica@Metal-Organic Framework and Applications for pH
Responsive Drug Delivery.
AB - Metal--organic frameworks (MOFs), a new type of porous crystalline material, hold
great potential in biomedical applications, such as drug delivery. However, the
efficacy of drug delivery is limited by low drug loading. In this work, we
synthesized hollow mesoporous silica (HMS)@MOF capsules that can be used as a pH
responsive drug delivery system for the anticancer drug doxorubicin (DOX). DOX is
loaded into the inner cavity of HMS. Zeolitic imidazolate framework-8 (ZIF-8)
nanoparticles are then coated on the outer surface of the DOX-loaded HMS. The
obtained material is a capsule (denoted as DOX/HMS@ZIF), in which DOX is
encapsulated. The DOX/HMS@ZIF can be used as an efficient pH-responsive drug
delivery system. DOX is not released under physiological conditions (pH 7.4), but
is released at low pH (4-6) from DOX/HMS@ZIF. The DOX/HMS@ZIF capsule shows much
higher cytotoxicity than free DOX and alters the delivery pathway for DOX in
cancer cells, while the drug-free HMS@ZIF shows excellent biocompatibility. This
opens new opportunities to construct a safe and efficient delivery system for
targeted molecules using pH-responsive release for a wide range of applications.
PMID- 29337423
TI - The next generation of melanocyte data: Genetic, epigenetic, and transcriptional
resource datasets and analysis tools.
AB - The number of melanocyte- and melanoma-derived next generation sequence genome
scale datasets have rapidly expanded over the past several years. This resource
guide provides a summary of publicly available sources of melanocyte cell derived
whole genome, exome, mRNA and miRNA transcriptome, chromatin accessibility and
epigenetic datasets. Also highlighted are bioinformatic resources and tools for
visualization and data queries which allow researchers a genome-scale view of the
melanocyte.
PMID- 29337424
TI - Enantiomeric separation of six chiral pesticides that contain chiral
sulfur/phosphorus atoms by supercritical fluid chromatography.
AB - Six chiral pesticides containing chiral sulfur/phosphorus atoms were separated by
supercritical fluid chromatography with supercritical CO2 as the main mobile
phase component. The effect of the chiral stationary phase, different type and
concentration of modifiers, column temperature, and backpressure on the
separation efficiency was investigated to obtain the appropriate separation
condition. Five chiral pesticides (isofenphos-methyl, isocarbophos, flufiprole,
fipronil, and ethiprole) were baseline separated under experimental conditions,
while isofenphos only obtained partial separation. The Chiralpak AD-3 column
showed a better chiral separation ability than others for chiral pesticides
containing chiral sulfur/phosphorus atoms. When different modifiers at the same
concentration were used, the retention factor of pesticides except flufiprole
decreased in the order of isopropanol, ethanol, methanol; meanwhile, the
retention factor of flufiprole increased in the order of isopropanol, ethanol,
methanol. For a given modifier, the retention factor and resolution decreased on
the whole with the increase of its concentration. The enantiomer separation of
five chiral pesticides was an "enthalpy-driven" process, and the separation
factor decreased as the temperature increased. The backpressure of the mobile
phase had little effect on the separation factor and resolution.
PMID- 29337425
TI - Distinct gene expression profiles and regulation networks of nasal polyps in
eosinophilic and non-eosinophilic chronic rhinosinusitis.
AB - BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is known to have 2
phenotypes in East Asia. Eosinophilic CRSwNP (ECRSwNP), defined as tissue
eosinophilia and easily recurrent, is distinguished from other non-eosinophilic
CRSwNP (NECRSwNP) types. However, the pathogenesis of each remains unclear.
METHODS: Nasal polyp tissues from ECRS (ECRSwNP) and NECRS (NECRSwNP) patients
were obtained, and their comprehensive gene expression profiles were investigated
by microarray analysis. Bioinformatics approaches (eg, Ingenuity Pathway Analysis
[IPA]) were used to interrogate the data sets. RESULTS: Hierarchical clustering
and principal component analysis (PCA) collectively showed that ECRSwNP and
NECRSwNP had distinct gene expression patterns. Of note, these genes could be
divided into 8 distinctive clusters having different expression patterns and
functions. Upstream Regulator Analysis revealed that not only T-helper 2 (Th2)
and the eosinophilia-related molecules (interleukin 4 [IL4], IL5, and colony
stimulating factor 2 [CSF2]) reported so far, but also cell cycle regulators
(cyclin dependent kinase inhibitor 1A [CDKNA1] and cyclin D1 [CCND1]) and a
tissue fibrosis-related molecule (transforming growth factor beta [TGFbeta]) were
identified in ECRSwNP. On the other hand, mainly interferons (IFNs) and acute
inflammatory cytokines (IL1 and IL6) were predicted as upstream regulators in
NECRSwNP. CONCLUSION: These results are useful for understanding the molecular
basis of the mechanisms of CRSwNP and point to new targets for developing
specific biomarkers and personalized therapeutic strategies for CRSwNP.
PMID- 29337426
TI - Prospective randomized study of conversion from tacrolimus to cyclosporine A to
improve glucose metabolism in patients with posttransplant diabetes mellitus
after renal transplantation.
AB - Tacrolimus (TAC) increases the risk of posttransplant diabetes (PTDM) compared
with cyclosporine A (CYC). The present 12-month, multicenter, investigator
driven, prospective, randomized study was designed to assess whether conversion
from tacrolimus to CYC can reverse PTDM after renal transplantation.
Predominantly white patients with PTDM according to the 2005 American Diabetes
Association criteria were randomized to either replacement of TAC with CYC or
continuation of their TAC-based regimen after stratification for type of glucose
lowering therapy, steroid therapy, and hepatitis C status. At 12 months, 14 of 41
patients with complete data in the CYC arm (34%; 95%CI 19%-49%) were free of
diabetes, whereas this was the case in only 4 of 39 patients (10%; 95%CI 3%-20%)
in the TAC arm (P = .01). At 12 months, 39% of patients in the CYC arm were off
glucose-lowering medication vs 13% of patients in the TAC arm (P = .01). The CYC
group decreased glycated hemoglobin level during the 12-month follow-up,
resulting in significantly lower levels compared with the TAC group (6.0 +/- 0.9%
vs 7.1 +/- 1.7% at 12 months; P = .002). In conclusion, replacement of TAC with
CYC significantly improves glucose metabolism and has the potential to reverse
diabetes during the first year after conversion. (EU Clinical Trials Register No.
2006-001765-42).
PMID- 29337427
TI - Outcomes From the First Helene Fuld Health Trust National Institute for Evidence
Based Practice in Nursing and Healthcare Invitational Expert Forum.
AB - BACKGROUND: Even though multiple positive outcomes are the result of evidence
based care, including improvements in healthcare quality, safety, and costs, it
is not consistently delivered by clinicians in healthcare systems throughout the
world. AIMS: In an attempt to accelerate the implementation of evidence-based
practice (EBP) across the United States, an invitational Interprofessional
National EBP Forum to determine major priorities for the advancement of EBP was
held during the launch of the newly established Helene Fuld Health Trust National
Institute for Evidence-Based Practice in Nursing and Healthcare at The Ohio State
University College of Nursing. METHODS: Interprofessional leaders from national
organizations and federal agencies across the United States were invited to
participate in the Forum. A pre-Forum survey was disseminated to participants to
assess their perceptions of the state of EBP and actions necessary to speed the
translation of research into real-world clinical settings. RESULTS: Findings from
a pre-Forum survey (n = 47) indicated ongoing low implementation of EBP in U.S.
healthcare settings. These findings were shared with leaders from 45
organizations and agencies who attended the Forum. Breakout groups on practice,
education, implementation science, and policy discussed the findings and
responded to a set of standardized questions. High-priority action tactics were
identified, including the need for: (a) enhanced reimbursement for EBP, (b) more
interprofessional education and skills building in EBP, and (c) leaders to
prioritize EBP and fuel it with resources. LINKING EVIDENCE TO ACTION: The
delivery of and reimbursement for evidence-based care must become a high national
priority. Academic faculty across all healthcare disciplines need to teach EBP,
healthcare systems must invest in EBP resources, and payers must attach
reimbursement to care that is evidence-based. An action collaborative of the
participating organizations has been formed to accelerate EBP across the United
States to achieve the quadruple aim in health care.
PMID- 29337428
TI - AP4 positively regulates LAPTM4B to promote hepatocellular carcinoma growth and
metastasis, while reducing chemotherapy sensitivity.
AB - Polymorphisms of the lysosomal-associated protein transmembrane-4 beta (LAPTM4B)
gene are related to various forms of tumour susceptibility, which led us to
hypothesize that some unique transcription factors targeting this polymorphism
region may affect the biological function of LAPTM4B in tumour progression. In
this study, we found that the transcription factor AP4 directly binds to the
polymorphism region of the LAPTM4B gene promoter and induces its transcription.
In addition, we demonstrated that AP4 promotes hepatocellular carcinoma (HCC)
cell proliferation and metastasis and depresses chemotherapy sensitivity via
LAPTM4B by activating the PI3K/AKT signalling pathway and caspase-dependent
pathway. Interestingly, we found that AP4 could not only regulate LAPTM4B by
directly binding to the promoter, but also be regulated via a positive feedback
mechanism involving LAPTM4B acting on c-myc. Finally, we showed that AP4 and
LAPTM4B are highly coexpressed in HCC tissues, and their coexpression may be a
marker of poor prognosis. These findings provide evidence of the expression and
functional coupling between AP4 and LAPTM4B and shed light on the regulation of
LAPTM4B and its function in liver cancer.
PMID- 29337429
TI - Co-Expression of ORFCma with PHB Depolymerase (PhaZCma ) in Escherichia coli
Induces Efficient Whole-Cell Biodegradation of Polyesters.
AB - Whole-cell degradation of polyesters not only avoids the tedious process of
enzyme separation, but also allows the degraded product to be reused as a carbon
source. In this study, Escherichia coli BL21(DE3) harboring phaZCma , a gene
encoding poly(3-hydroxybutyrate) (PHB) depolymerase from Caldimonas
manganoxidans, is constructed. The extra-cellular fraction of E. coli/pPHAZ
exhibits a fast PHB degradation rate where it only took 35 h to completely
degrade PHB films, while C. manganoxidans takes 81 h to do the same. The co
expression of ORFCma (a putative periplasmic substrate binding protein that is
within the same operon of phaZCma ) further improves the PHB degradation. While
28 h is needed for E. coli/pPHAZ to cause an 80% weight loss in PHB films, E.
coli/pORFPHAZ needs only 21 h. Furthermore, it is able to degrade at-least four
different polyesters, PHB, poly(lactic acid) (PLA), polycaprolactone (PCL), and
poly(butylene succinate-co-adipate) (PBSA). Testing of the time course of 3
hydroxybutyrate concentration and the turbidity of the degradation solutions over
time shows that PhaZCma has both exo- and endo-enzymatic activity. The whole-cell
E. coli/pORFPHAZ can be used for recycling various polyesters while ORFCma can
potentially be a universal element for enhancing the secretion of recombinant
protein.
PMID- 29337431
TI - Spotlights on our sister journals: Angew. Chem. Int. Ed. 4/2018.
PMID- 29337430
TI - Corrigendum: Interband Absorption Enhanced Optical Activity in Discrete Au@Ag
Core-Shell Nanocuboids: Probing Extended Helical Conformation of Chemisorbed
Cysteine Molecules.
PMID- 29337432
TI - Corrigendum: Nanoscale Control of Homoepitaxial Growth on a Two-Dimensional
Zeolite.
PMID- 29337433
TI - Numerical simulation of two consecutive nasal respiratory cycles: toward a better
understanding of nasal physiology.
AB - BACKGROUND: Computational fluid dynamic (CFD) simulations have greatly improved
the understanding of nasal physiology. We postulate that simulating the entire
and repeated respiratory nasal cycles, within the whole sinonasal cavities, is
mandatory to gather more accurate observations and better understand airflow
patterns. METHODS: A 3-dimensional (3D) sinonasal model was constructed from a
healthy adult computed tomography (CT) scan which discretized in 6.6 million
cells (mean volume, 0.008 mm3 ). CFD simulations were performed with
ANSYS(c)FluentTMv16.0.0 software with transient and turbulent airflow (k-omega
model). Two respiratory cycles (8 seconds) were simulated to assess pressure,
velocity, wall shear stress, and particle residence time. RESULTS: The pressure
gradients within the sinus cavities varied according to their place of connection
to the main passage. Alternations in pressure gradients induced a slight pumping
phenomenon close to the ostia but no movement of air was observed within the
sinus cavities. Strong movements were observed within the inferior meatus during
expiration contrary to the inspiration, as in the olfactory cleft at the same
time. Particle residence time was longer during expiration than inspiration due
to nasal valve resistance, as if the expiratory phase was preparing the next
inspiratory phase. Throughout expiration, some particles remained in contact with
the lower turbinates. The posterior part of the olfactory cleft was gradually
filled with particles that did not leave the nose at the next respiratory cycle.
This pattern increased as the respiratory cycle was repeated. CONCLUSION: CFD is
more efficient and reliable when the entire respiratory cycle is simulated and
repeated to avoid losing information.
PMID- 29337434
TI - Light and darkness in circadian rhythms.
PMID- 29337435
TI - Hyalinosis cutis et mucosae: A clinical investigation with special regard to
mucosal changes.
PMID- 29337436
TI - Integrating TEMPO and Its Analogues with Visible-Light Photocatalysis.
AB - Visible light has risen to become a very important facilitator for selective
radical reactions enabled by well-cognized photocatalysts. The renaissance of
visible-light photocatalysis on this matter partly relies on integrating it with
other fields of catalysis. In parallel, 2,2,6,6-tetramethylpiperidin N-oxide
(TEMPO), a quintessential persistent radical, has a wide range of uses owing to
its exceptional redox behavior, which gives rise to its latest prominence in
catalysis. Therefore, integrating the catalysis of TEMPO with photocatalysis to
perform visible-light-induced selective reactions becomes a very convenient
marriage of merits. In this context, the integration of different types of
photocatalysts, including metal complexes, metal-free organic dyes, and
semiconductors, with TEMPO for outstanding organic transformations will be
summarized. To expand further the catalytic repertoire, the integration of TEMPOH
analogues such as NHPI (N-hydroxyphthalimide) and NHS (N-hydroxysuccinimide) with
photocatalysis will also be discussed. Hopefully, these advances will pave the
way for more breakthroughs by integrating TEMPO and its analogues with
photocatalysis to lead to a valuable blueprint for visible-light-induced
selective organic transformations.
PMID- 29337437
TI - Canonical signaling and nuclear activity of mTOR-a teamwork effort to regulate
metabolism and cell growth.
AB - Mechanistic (or mammalian) target of rapamycin (mTOR) is a kinase that regulates
almost all functions related to cell growth and metabolism in response to extra-
and intracellular stimuli, such as availability of nutrients, the presence of
growth factors, or the energy status of the cell. As part of two distinct protein
complexes, mTORC1 and mTORC2, the kinase has been shown to influence cell growth
and proliferation by controlling ribosome biogenesis, mRNA translation,
carbohydrate and lipid metabolism, protein degradation, autophagy as well as
microtubule and actin dynamics. In addition to these well-characterized
functions, mTOR can also influence gene transcription. While most studies focused
on investigating how canonical mTOR signaling regulates the activity of
transcription factors outside the nucleus, recent findings point to a more direct
role for mTOR as a transcription factor operating on chromatin in the nucleus. In
particular, recent genome-wide identification of mTOR targets on chromatin
reveals that its activities in the nucleus and cytoplasm are functionally and
biologically linked, thus uncovering a novel paradigm in mTOR function.
PMID- 29337439
TI - ?
PMID- 29337440
TI - [Addictions].
AB - This year, the actuality for addictions in this edition addresses four points.
The disease model of addiction is criticized by the cognitive neurosciences which
need to consider the agentivity of the persons. Regarding the societal actuality,
clinical pharmacology review of cannabidiol presents an update on legal cannabis.
The suicidality of excessive gamblers may be prevented specifically. Addiction
and first psychotic episodes need an integrated care.
PMID- 29337438
TI - 3D-e-Chem: Structural Cheminformatics Workflows for Computer-Aided Drug
Discovery.
AB - eScience technologies are needed to process the information available in many
heterogeneous types of protein-ligand interaction data and to capture these data
into models that enable the design of efficacious and safe medicines. Here we
present scientific KNIME tools and workflows that enable the integration of
chemical, pharmacological, and structural information for: i) structure-based
bioactivity data mapping, ii) structure-based identification of scaffold
replacement strategies for ligand design, iii) ligand-based target prediction,
iv) protein sequence-based binding site identification and ligand repurposing,
and v) structure-based pharmacophore comparison for ligand repurposing across
protein families. The modular setup of the workflows and the use of well
established standards allows the re-use of these protocols and facilitates the
design of customized computer-aided drug discovery workflows.
PMID- 29337441
TI - [Allergology and clinical immunology].
AB - Hereditary angioedema (HA) is a disabling and potentially fatal condition. The
management of HA includes treatment of acute attacks, short-term prophylaxis to
prevent an attack, and long-term prophylaxis to minimize the frequency and
severity of recurrent attacks. In this article, we will present new therapeutic
alternatives for long term prophylaxis. Glucocorticoids (GC) usage leads to a
number of severe side-effects. In giant cell arteritis, the use of tocilizumab in
conjunction with low doses of GC reduces the number of relapses. In ANCA
associated vasculitis the use of an anti-C5R (avacopan) alone or in conjunction
with low doses of GC results in similar remission rates to those induced by high
dose GC.
PMID- 29337442
TI - [Angiology and haemostasis. Highlights on some new data in 2017].
AB - New data support the fact that prophylactic anticoagulation with direct oral
anticoagulants is effective and safe for the long-term prevention of venous
thromboembolism. This type of treatment is dedicated for a subgroup of patients
only, which is described in this article. With regard to major bleedings
occurring with these anticoagulants, new data have been added to those already
available for idarucizumab, a specific antagonist of dabigatran. Finally, we
summarize the data regarding a breakthrough molecule, emicizumab, which could
potentially open a new era in the management of people with haemophilia A.
PMID- 29337444
TI - [Fumarates - far more than a dietary supplement].
AB - Fumaric acid has an important role in the citric acid cycle. Its esters were
first used by a German chemist to treat his own psoriasis, hypothesizing that the
disease may be related to disturbances in this very cycle. Meanwhile, the
mechanisms underlying its anti-inflammatory efficacy are much better understood.
A monosubstance derived from the mix of esters used originally is now being
authorized for treating multiple sclerosis, and in 2017 dimethylfumaric acid
ester became a globally available option to treat psoriasis. This very practical
therapeutic will most likely become quite popular amongst patients. Therefore,
general practitioners might need to familiarize themselves with the profile of
this drug, including its potential risks and some very rare but potentially
important adverse effects.
PMID- 29337443
TI - [Update in Surgical Oncology].
AB - In 2017, data from large multicentre randomized controlled trials assessed the
safety of minimally invasive techniques for liver or esophagus resection with
similar oncologic outcome compared to open approach. Patients also benefit from
progress in medical oncology in particular with the development of new targeted
therapies, offering surgery to patients with initially non-resectable disease.
The increase in complete tumor response after neoadjuvant treatment allows more
conservative approaches, like organ preserving surgery for rectal cancer. The
constant improvement in perioperative care and enhanced recovery programs
(Enhanced Recovery After Surgery - ERAS) reduce both length of hospital stay and
costs, decrease the risk of postoperative complications, and offer better quality
of life to the patients.
PMID- 29337445
TI - [News in diabetology 2017].
AB - The field of diabetes is constantly evolving, with numerous new molecules
reaching the market for the treatment of type 2 diabetes. Paradoxically, this
drug jungle is difficult for the primary care physician and can lead to
therapeutic inertia. The aim of this article is to discuss new molecules and new
cardiovascular outcome studies that lead to changes in guidelines pertinent to
the pharmacological treatment of type 2 diabetes.
PMID- 29337446
TI - [Endocrinopathies induced by immune checkpoint inhibitors].
AB - Immune checkpoint Inhibitors are new immunomodulatory treatments that have proven
their anti-tumor efficacy in several advanced cancers. Nevertheless, their use
has paved the way for multiple immunological adverse effects that affect many
systems and organs including endocrine glands such as the pituitary, thyroid,
adrenal and pancreas. Hypophysitis is the most common complication of anti-CTLA-4
monoclonal antibodies, while anti-PD-1 and anti-PD-L1 antibodies cause more
thyroid complications. Adrenal insufficiency and type 1 diabetes are relatively
less common. Endocrinologists and primary care physicians as well as oncologists
are likely to deal with these complications and as such, knowledge of these drugs
and their side effects is essential for good practice.
PMID- 29337447
TI - [Geriatric medicine].
AB - 2017 highlights benefits of prevention. Better control of cardiovascular risk
reduces the incidence of dementia and monthly high-dose vitamin D the incidence
of respiratory infections in nursing home. Pre-operative geriatric assessment
lowers by 20% the rate of delirium after hip-fracture surgery and complications
in vascular surgery. Deleterious effects are also reported. High-dose vitamin D
triples the rate of falls in supplemented residents and doesn't improve gait
speed in sedentary men. Widely used in cardiovascular prevention, antithrombotic
therapy is associated with an astonishing risk of subdural bleeding that further
increases with the number of drugs combined together. Finally, the non
pharmacological management of behavioral and psychotic symptoms in advanced
dementia, although effective, doesn't reduce the associated burden for proxies.
PMID- 29337448
TI - [Obstetrics].
AB - During the past year, we have renewed interest in old well-known problems. New
studies and guidelines have been issued about lung maturation in cases of preterm
delivery after 37 weeks of gestation. Short term benefits have been proven but
the number of cases needed to treat to prevent one case of respiratory
complications is high and with possible neurological long-term effects. Also,
several studies have shown the benefits of including the ultrasound measurement
of the inferior segment of the uterus in order to attempt vaginal delivery after
caesarean section with the lowest risk for uterine rupture, while others studies
have shown the best procedure to close the uterus during cesarean section. And
finally, we will discuss about an old friend: aspirin to reduce the risk of pre
eclampsia.
PMID- 29337449
TI - [Blood pressure management : what's new in 2017 ?]
AB - In the last 2 years, the attention of hypertension specialists has been focused
on the results of the SPRINT trial and its post-hoc analyses and its possible
implications for the management of hypertensive patients. While waiting for new
European hypertension guidelines due in 2018, the year 2017 can be considered as
a year of transition. Yet, several interesting clinical studies have been
published which may affect the future management of hypertension. Thus we shall
discuss new data on the benefits of eating more fruits and vegetables on
cardiovascular mortality, the " quadpill " concept, the impact of various non
steroidal anti-inflammatory drugs on blood pressure and the most recent data on
renal denervation.
PMID- 29337450
TI - [Emergency medicine : update 2017].
AB - Emergency medicine is part of the current stream of efficient and qualitative
medicine : 1) the modified Valsava maneuver results in the resolution of almost
50% of supra-ventricular tachycardia without any drug; 2) lung echography
performed by emergency physicians is a very sensitive and specific diagnostic
tool for most thoracic emergencies; 3) cardiopulmonary resuscitation initiated by
lay-rescuers improves short and long-term outcome; 4) no anticoagulant treatment
is warranted in distal deep vein thrombosis and 5) systematic unenhanced
abdominal CT might improve evaluation of elderly patients with acute abdominal
pain.
PMID- 29337451
TI - [Nephrology].
AB - New antidiabetic drugs which slow effectively the course of diabetic nephropathy
are now available. There is no benefit of prophylactic hydratation to prevent
contrast nephropathy in patients with moderate chronic kidney disease. In elderly
hemodialysis patients, hemodiafiltration seems better tolerated than conventional
hemodialysis, although there is a similar dialysis-induced myocardial stress with
both methods. Role of de novo donor-specific antibodies is better characterized,
which may subsequently lead to new treatments of graft rejection.
PMID- 29337452
TI - [Neurology].
AB - Ocrelizumab (Ocrevus), an anti-CD20 monoclonal antibody, has been approved for
the treatment of multiple sclerosis. Eculizumab (Soliris) has been approved in
several countries for refractory forms of generalized seropositive severe
myasthenia gravis. A form of gene therapy, patisiran, has shown positive results
in transthyretin familial amyloidosis. In the treatment of headaches,
particularly migraines, non-pharmacological approaches have shown some
interesting results. The criteria for Lewy body dementia have been revised.
Generic use of lamotrigine does not result in recrudescence of epileptic seizures
or adverse effects.
PMID- 29337453
TI - [AMD and complement pathway in 2017].
AB - AMD is the major cause of visual loss in individuals older than 50 in the western
countries. Whilst tremendous progress has been made by the intraocular repeated
injections of anti-VEGFs in wet AMD, no treatment is recognized to prevent
progression of dry AMD, which represents more than 50 % of the cases.
Interestingly, an over activation of the complement alternative pathway has been
associated to both forms of AMD. But, several clinical studies have failed to
demonstrate any efficacy of molecules blocking the complement pathway at various
stage of its activation. In 2017, another failure was reported with lampalizumab
after this drug succeeded in phase 2. Why such failure? What is the exact role of
complement in AMD pathogenesis? Is complement regulation a hopeless pathway to
follow in AMD? This article summarizes knowledge in the field.
PMID- 29337454
TI - [Osteoporosis].
AB - The risk for a second fracture within two years after a first one is high. Ten
years denosumab treatment show favorable results with a risk of early vertebral
fractures in patients with prevalent vertebral fractures when treatment is
stopped. Teriparatide is more effective than risedronate to prevent vertebral and
clinical fractures in high risk patients. Romosozumab acts as an anabolic agent
in osteoporosis. Atypical femoral fractures associated with bisphosphonate
treatment could be more frequent in patients with particular anatomical features.
Management of osteoporosis treatment depends on the drug which is used and on the
risk of fracture of the patient.
PMID- 29337455
TI - [Pediatrics - New classification of seizures and epilepsies].
AB - The International League Against Epilepsy published a new classification of
epileptic seizures and epilepsies. It is more transparent and important notions
like etiologies and comorbities have been added. The identification of seizures,
epilepsies then epilepsy syndromes constitutes the three steps of this
classification.
PMID- 29337456
TI - [Pediatrics - Perthes disease : current knowledges and treatment].
AB - Perthes's disease corresponds to an interruption of the vascularization of the
epiphyseal nucleus of the femoral head followed by avascular necrosis. This
necrosis weakens the bone and subchondral fractures associated with a deformation
of the femoral head is seen. It is important not to miss an extrusion of the
femoral head, which makes surgical treatment unavoidable. The loss of joint
congruence causes functional limitations and represents an increased risk for
early hip osteoarthritis. Non weight bearing limits the subchondral fractures,
but requires an important adaptation from the patient and his entourage.
PMID- 29337457
TI - [Pharmacovigilance update].
AB - The main pharmacovigilance updates in 2017 are reviewed. Denosumab : rebound
associated multiple vertebral fractures after discontinuation. Canagliflozine:
increased risk of foot/leg amputations. Biologic and targeted cancer therapies,
direct-acting antivirals for chronic hepatitis C: risk of hepatitis B
reactivation. Checkpoint inhibitors : immune-related adverse events and graft
rejection. Fingolimod : rebound-associated reactivation of MS following
withdrawal. Daclizumab: risk of severe liver injury leading to restricted use in
MS patients. Posaconazole: risk of overexposure when switching from oral
suspension to tablets. Voriconazole: cutaneous squamous cell carcinoma under long
term therapy. Proton pump inhibitors : early exposure might increase fracture
risk in young children.
PMID- 29337458
TI - [Pulmonary diseases. Asthma, COPD and sleep apnea syndrome].
AB - Among the novelties described in the management of pulmonary disorders during the
year 2017, we chose to describe three. First, the indication for inhaled
glucocorticosteroids (ICS) in COPD has been revisited, because of their
relationship with an increased occurence of pneumonia : ICS are now recommended
only in severe COPD (GOLD D) with frequent exacerbations as second line
treatment. Secondly, azithromycine has shown very promising results in poorly
controlled severe asthma, with a significant impact on symptoms and
exacerbations. Finally, despite the association between sleep apnea syndrome and
cardiovascular morbidity, the prescription of CPAP in asymptomatic individuals as
primary or secondary prevention is not supported by the recent literature.
PMID- 29337459
TI - [Psychiatry].
AB - Children of patients with psychiatric disorders are at higher risk to develop a
psychiatric illness. In addition, phases of crisis and hospitalization of the
parent are often traumatizing to the children, especially during childhood.
Although a specific offer to face these issues is compulsory in some countries,
such is not the case in Switzerland. In this paper we describe the implementation
of a special offer for children of parents with mental illness (Famille +) in the
service of general psychiatry at the Department of psychiatry of the Lausanne
University hospital in Switzerland. We will also discuss the development and
implementation of the Joint Crisis Plan, a collaborative tool where psychiatric
patients and clinicians define the strategies that should be applied in case of
crisis, which strengthens the empowerment of patients and their participation to
decisions about their treatment.
PMID- 29337460
TI - [Rheumatology. Checkpoint-induced autoimmunity - birth of a new disease].
AB - Tumor cells express checkpoint proteins in order to prevent an immune reaction by
T-cells. Checkpoint inhibitors are successfully used in oncology to unleash a
cytotoxic immune response. Unfortunately this treatment increasingly leads to
immune-related adverse events which resemble various primary autoimmune disorders
known in rheumatology. Potentially, checkpoint dysfunction also underlies
rheumatic diseases which would open the way for new treatment options to restore
immune tolerance.
PMID- 29337461
TI - [Urology].
AB - This article points at recent developments in urology in the field of malignant
diseases of the urinary system and the diagnostic and therapeutic management of
benign conditions as well, that occur frequently in our ageing population.
PMID- 29337462
TI - [Antiretroviral treatments : towards simplified regimens ?]
AB - The chronicity of HIV infection and the use of antiretroviral therapy among all
individuals living with HIV necessitate new treatment strategies. Alternatives to
lifelong tri-therapy treatment are under investigation with the aim to improve
the quality of life of patients. New therapies with longer half-lives or "
biological " treatments are also under study in clinical trials in order to
develop streamlined maintenance strategies. These simplified therapies represent
the near future of HIV management both with regards to less toxic molecules and a
change in the traditional dogma of tri-therapy, including the daily dose thanks
to the possibility of dosage only on certain weekdays or via molecules under
development with a long duration of action.
PMID- 29337463
TI - [Virtual reality: a tool that can be used in outpatient diabetes services].
AB - Health-related emerging technologies are growing fast. The use of virtual reality
in diabetes outpatient care still remains unprecedented, notably in Switzerland.
Thus, the Programme cantonal Diabete led a pilot study to assess the feasibility
of an immersive application in such an outpatient setting. Results emphasize that
this device is practicable and useful in diabetes care. Patients and their
relatives overall appreciate the game, each of them for specific reasons: playful
quality, opportunity to " learn differently " or to exchange about the subjective
experience. Furthermore, there is no restraint (age, language, educational
level...) in the ability to use such a device, except for emerging technologies
habit.
PMID- 29337464
TI - ?
PMID- 29337465
TI - ?
PMID- 29337466
TI - ?
PMID- 29337467
TI - ?
PMID- 29337468
TI - ?
PMID- 29337469
TI - ?
PMID- 29337470
TI - Multifunctional pH-Responsive Folate Receptor Mediated Polymer Nanoparticles for
Drug Delivery.
AB - Multifunctional pH-responsive folate receptor mediated targeted polymer
nanoparticles (TPNps) were developed for docetaxel (DTX) delivery based on
poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene
glycol)poly (beta-amino ester) (P123-PAE) and poly(ethylene glycol)-block
poly(propylene glycol)-block-poly(ethylene glycol)-folate (P123-FA) copolymers.
The DTX was loaded into the TPNps with a decent drug loading content of 15.02 +/-
0.14 wt%. In vitro drug release results showed that the DTX was released from the
TPNps at a pH-dependent manner. Tetrazolium dye (MTT) assay revealed that the
bland polymer nanoparticles displayed almost nontoxicity at 200 MUg/mL
concentration. However, the DTX-loaded TPNps showed high anti-tumor activity at
low IC50 (0.72 MUg/mL) for MCF-7 cells following 48 h incubation. Cellular uptake
experiments revealed that the TPNps had higher degree of cellular uptake than
nontargeted polymer nanoparticles, indicating that the nanoparticles were
internalized into the cells via FA receptor-mediated endocytosis. Moreover, the
cellular uptake pathways for the FA grafted polymer were involved in energy
dependent, clathrin-mediated and caveolae-mediated endocytosis. The cell killing
effect and cellular uptake of the DTX-TPNps by the MCF-7 cells were all enhanced
by about two folds at pH 5.5 when compared with pH 7.4. The TPNps also
significantly prolonged the in vivo retention time for the DTX. These results
suggest that the biocompatible pH responsive folate-modified polymer
nanoparticles present a promising safe nanosystem for intracellular targeted
delivery of DTX.
PMID- 29337484
TI - Simultaneous Targeting of Differentiated Breast Cancer Cells and Breast Cancer
Stem Cells by Combination of Docetaxel- and Sulforaphane-Loaded Self-Assembled
Poly(D, L-lactide-co-glycolide)/Hyaluronic Acid Block Copolymer-Based
Nanoparticles.
AB - Breast cancer stem cells (BCSCs) are implicated in the initiation and progression
of breast cancer and are responsible for metastasis and recurrence. In this
study, we attempted to simultaneously target differentiated breast cancer cells
(DBCCs) and BCSCs by using a combination of docetaxel (DTX)- and sulforaphane
(SFN)-loaded poly(D, L-lactide-coglycolide)/hyaluronic acid (PLGA-b-HA)-based
nanoparticles. BCSCs were identified as having an ESA+CD44+CD24- phenotype, which
exhibited docetaxel resistance. Drug-loaded nanoparticles exhibited enhanced
cytotoxicity towards both DBCCs and BCSCs compared with free drugs. SFN-loaded
nanoparticles were more effective in inhibiting BCSCs than free SFN in vitro by
down-regulating beta-catenin expression. In vivo analysis of anti-tumor activity
showed that the combination therapy with DTX- and SFN-loaded nanoparticles had
the strongest antitumor efficacy. In vivo analysis of anti-BCSCs activity showed
that the self-renewal ability of BCSCs was strongly inhibited in DTX- and SFN
loaded nanoparticle-treated groups. In conclusion, the combination of SFN- and
DTX-loaded PLGA-b-HA nanoparticles shows therapeutic potential in the treatment
of breast cancer by simultaneously targeting DBCCs and BCSCs.
PMID- 29337485
TI - A Novel Thermochromic Liquid Crystal Fabric Design for the Early Detection of
High-Risk Foot Complications
AB - Background: We developed a prototype of a novel thermochromic liquid crystal
(TLC)-coated fabric with an extended temperature range and enhanced sensitivity.
By incorporating color and pattern recognition into the fabric, rapid
determination of the underlying pedal temperature is facilitated. The purpose of
this study was to evaluate the accuracy of the TLC fabric as a potential
diagnostic aid for identifying complications in the high-risk foot. Methods: The
hands of 100 individuals were used to compare the mean maximum temperatures
indicated by the fabric versus standard thermal camera images. Findings were
statistically analyzed using a paired t test, with significance
defined as P < .05. Results: Except for the tip of the thumb and
regions in the palm, there were no statistically significant differences between
mean maximum temperatures measured with the thermal camera and those detected
with the TLC fabric. Minor differences were relatively consistent in all nine
regions of the hand and were not considered to be clinically significant.
Conclusions: Using direct visual analysis, we demonstrated that a novel TLC
fabric could accurately map temperatures in the palmar surface of the hand. The
findings support the continued development of a temperature-sensitive sock that
can be used in the home to monitor for temperature changes that may indicate the
onset of complications in the high-risk foot.
PMID- 29337486
TI - Improving risk stratification among veterans diagnosed with prostate cancer:
impact of the 17-gene prostate score assay.
AB - BACKGROUND: Active surveillance (AS) has been widely implemented within Veterans
Affairs' medical centers (VAMCs) as a standard of care for low-risk prostate
cancer (PCa). Patient characteristics such as age, race, and Agent Orange (AO)
exposure may influence advisability of AS in veterans. The 17-gene assay may
improve risk stratification and management selection. OBJECTIVES: To compare
management strategies for PCa at 6 VAMCs before and after introduction of the
Oncotype DX Genomic Prostate Score (GPS) assay. STUDY DESIGN: We reviewed records
of patients diagnosed with PCa between 2013 and 2014 to identify management
patterns in an untested cohort. From 2015 to 2016, these patients received GPS
testing in a prospective study. Charts from 6 months post biopsy were reviewed
for both cohorts to compare management received in the untested and tested
cohorts. SUBJECTS: Men who just received their diagnosis and have National
Comprehensive Cancer Network (NCCN) very low-, low-, and select cases of
intermediate-risk PCa. RESULTS: Patient characteristics were generally similar in
the untested and tested cohorts. AS utilization was 12% higher in the tested
cohort compared with the untested cohort. In men younger than 60 years,
utilization of AS in tested men was 33% higher than in untested men. AS in tested
men was higher across all NCCN risk groups and races, particular in low-risk men
(72% vs 90% for untested vs tested, respectively). Tested veterans exposed to AO
received less AS than untested veterans. Tested nonexposed veterans received 19%
more AS than untested veterans. Median GPS results did not significantly differ
as a factor of race or AO exposure. CONCLUSIONS: Men who receive GPS testing are
more likely to utilize AS within the year post diagnosis, regardless of age,
race, and NCCN risk group. Median GPS was similar across racial groups and AO
exposure groups, suggesting similar biology across these groups. The GPS assay
may be a useful tool to refine risk assessment of PCa and increase rates of AS
among clinically and biologically low-risk patients, which is in line with
guideline-based care.
PMID- 29337487
TI - Production of Nanoscale Vibration for Stimulation of Human Mesenchymal Stem
Cells.
AB - Mechanical stimulation is becoming a common technique for manipulating cell
behaviour in bioengineering with applications in tissue engineering and possibly
regenerative therapy. Living organisms show biological responses in vivo and in
vitro to various types of mechanical stimulation including vibration. The
development of apparatus to produce vertical motions of nanoscale amplitude is
detailed and their effect on mouse endothelial (Le2) and human mesenchymal stem
cells (hMSCs) is investigated. Piezo ceramic actuators and aluminium
reinforcement were utilised along with laser interferometry to ensure amplitude
consistency at the nanometre level across a cell culture substrate. Peak force
applied to the cells was estimated to be of nN magnitude at frequencies of 500
and 1000 Hz. Morphological changes in the cytoskeleton were found for both cell
types along with increased MSC proliferation after 1 week of stimulation at 500
Hz. Changes in the nuclear size of MSCs after stimulation were also found.
PMID- 29337488
TI - Optimization of Transforming Growth Factor-beta1 siRNA Loaded Chitosan
Tripolyphosphate Nanoparticles for the Treatment of Colorectal Cancer Hepatic
Metastasis in a Mouse Model.
AB - Metastatic liver disease is the most frequent complication of colorectal cancer
(CRC), and the development of liver-targeted nanoparticles for drug delivery is a
promising therapeutic approach. However, to improve the efficacy of passive drug
delivery, its release rate at the sites of liver metastases should be maximized
while minimizing drug uptake in nontargeted cells. Herein, we report the
development and use of tripolyphosphate (TPP) modified chitosan (CS)
nanoparticles loaded with small interfering RNA (siRNA) directed against
transforming growth factor beta1 (TGF-beta1), which promotes tumorigenesis in
advanced CRC. The nanoparticles efficiently inhibited CRC hepatic metastasis in
an animal model. Particles of 300 nm in size and zeta potential at 20 mV showed a
more striking liver-targeting effect. A weight ratio of CS/TPP of 8:1 for
particles with TGF- beta1 siRNA loaded at a concentration of 20 MUM at pH 7.5
showed good pH-responsive drug release when exposed to a CRC homogenate at pH
6.5. In vivo, CS-TPP/TGF- beta1 siRNA nanoparticles significantly reduced the
volume and number of CRC metastatic foci. This was accompanied by the
downregulation of TGF- beta1 expression in the tumor microenvironment, inhibition
of tumor associated macrophage formation, and improvement of the immune
microenvironment. These results indicate that it is possible to achieve effective
passive liver targeting by optimizing the processing parameters. The design of
nanoparticles carrying siRNA against overexpressed oncogenes provides an
excellent platform for the development of an efficient liver cancer therapy.
PMID- 29337489
TI - An Investigation of the Usability of Solid Lipid Nanoparticles Radiolabelled with
Tc-99m as Imaging Agents in Liver-Spleen Scintigraphy.
AB - In this work, solid lipid nanoparticles (SLNs) were prepared by microemulsion and
ultrasonication methods in the first stage of the production process of 99mTc
SLNs, which is considered to be an alternative radiopharmaceutical for the liver
spleen scintigraphy within the nuclear medicine. The laser diffraction (LD) and X
ray diffraction (XRD) analysis showed that these particles were at nano scale and
had beta' polymorph structure, respectively. It was observed that there was no
interaction between the solid lipid and the surfactant molecules by fourier
transform infrared spectroscopy (FT-IR). The scanning electron microscope (SEM)
and transmission electron microscopy (TEM) images were taken and seen that the
SLNs were spherical and at nano scale. Thermogravimetric analysis (TGA) for
stability confirmed that they were stable for temperature variations. In the
second stage of the study, the SLNs were successfully labeled with 99mTc. The
radiolabeling efficiency was found to be greater than %95 and in vivo studies
were performed on experimental rabbits using scintigraphic methods. When the
obtained images were examined, the uptake was observed in the heart, the lungs,
the liver, and the spleen. It was concluded that SLNs labeled with 99mTc could be
a selective imaging agent. It was asserted to be a new radiopharmaceutical,
especially as an alternative to the 99mTc-labeled compounds used in the liver and
spleen imaging in colloid scintigraphy.
PMID- 29337490
TI - PEG-Poly(amino acid)s/MicroRNA Complex Nanoparticles Effectively Arrest the
Growth and Metastasis of Colorectal Cancer.
AB - One of the biggest challenges in developing microRNA (miRNA) based therapeutics
is the method of delivery. Herein we report the design and synthesis of mPEG
poly(amino acid)s, which we used as a novel nanocarrier for the delivery of miRNA
139-5p. The PEG-poly(amino acid)s/miRNA-139-5p nanoparticle complex is more
effective at suppressing tumor growth and migration in mice with colorectal
cancer than when treated with miRNA-139-5p solution and blank nanoparticles
individually. Our results suggest that PEG-poly(amino acid)s are a promising non
viral gene vector for the delivery of miRNAs to treat cancers.
PMID- 29337491
TI - Gold Nanocrystals with Well-Defined Crystallographic {111} Facets Suppress
Pathological Neovascularization.
AB - Vascular endothelial growth factor (VEGF) is a main factor in pathological
neovascularization in various human diseases including age-related macular
degeneration, cancer, and diabetic complications. Interestingly, gold nanospheres
are known to bind to VEGF and to suppress VEGF-mediated angiogenesis. The anti
angiogenic effects are known to be governed by the size and surface charge of the
nanoparticles. However, studies on the role of the shape in biological actions
are limited. In this study, we investigate the anti-angiogenic properties of
nanocrystals that have well-defined crystallographic {111} facets. Single
crystalline icosahedral and octahedral gold nanocrystals effectively scavenge
VEGF just as nanospheres with similar diameter. In addition, they suppress the in
vitro VEGF-induced activation of the VEGF receptor and the proliferation of
endothelial cells. They also significantly inhibit in vivo VEGF-mediated retinal
vascular permeability. These results thus suggest that gold nanocrystals with
{111} facets can provide a useful platform for nanoparticle-based treatment of
VEGF-driven pathological neovascularization beyond their current optical and
catalytic applications.
PMID- 29337492
TI - Nanoparticle-Based Mucosal Vaccines Targeting Tumor-Associated Antigens to Human
Dendritic Cells.
AB - The induction of effective T cell-mediated immune responses is the main objective
of vaccination against cancer. T cell responses are initiated by dendritic cells
(DCs) as the most potent antigen-presenting cells. Designing vaccines for
efficient delivery of tumor antigens to these cells in immunogenic fashion is,
therefore, a major task in tumor immunology. In this human-based in vitro study
we investigated the suitability of different polymeric nanoparticles (NPs) for
delivering the tumor-associated antigen Her2/neu to DCs for induction of T cell
responses by mucosal vaccination. The natural polymer chitosan and novel
functionalized PLGA-based polymers were used for NP production. All NPs were
efficiently taken up by DCs. Her2/neu delivered by NPs was more efficiently
processed and presented by DCs than the soluble protein and induced more vigorous
CD4+ and CD8+ T cell proliferation, and cytotoxic T cells. Testing the
suitability of this platform for mucosal vaccination, NPs were applied to the
apical side of an intestinal epithelium model and found to be efficiently
transported across the epithelial layer to become available to basolateral DCs.
Thus, chitosan and PLGA-based NPs are efficient carriers for delivery of antigens
to DCs for induction of T cell-based immunity, and suitable for mucosal vaccine
formulations.
PMID- 29337493
TI - Cellular Internalization Mechanisms of Polyanhydride Particles: Implications for
Rational Design of Drug Delivery Vehicles.
AB - Polyanhydride nanoparticles have emerged as a versatile delivery platform, due to
their ability to encapsulate diverse drugs, immunogens, antibodies, and proteins.
However, mechanistic studies on the effects of particle chemistry interactions
with immune cells have yet to be described. Understanding the mechanism by which
these particles are internalized by immune cells will enable rational selection
of delivery vehicles for specific applications. In the present study, the
internalization, mechanism(s) of uptake by monocytes, and intracellular fate of
polyanhydride nanoparticles were evaluated using copolymers based on 1,6-bis(p
carboxyphenoxy)hexane (CPH), sebacic acid (SA), and 1,8-bis(p-carboxyphenoxy)3,6
dioxaoctane (CPTEG). The results showed that 20:80 CPH:SA and 20:80 CPTEG:CPH
nanoparticles were internalized to a greater extent by monocytes as compared to
the 50:50 CPH:SA and 50:50 CPTEH:CPH nanoparticles. Further, cytochalasin-D
treatment of cells inhibited uptake of all the particles, regardless of
chemistry, indicating that actinmediated uptake is the primary mechanism of
cellular entry for these particles. The insights gained from these studies were
used to identify lead nanoparticle formulations to enhance treatment of
intracellular bacterial infections. The use of doxycycline-loaded nanoparticles
exhibited enhanced therapeutic efficacy compared to soluble drug in treating
monocyte monolayers infected with the virulent intracellular pathogen Brucella
abortus. Altogether, these studies demonstrate how rational design and selection
of nanoscale delivery platforms can be used for a wide spectrum of biomedical
applications.
PMID- 29337526
TI - Carbon Nanotube Web with Carboxylated Polythiophene "Assist" for High-Performance
Battery Electrodes.
AB - A carbon nanotube (CNT) web electrode comprising magnetite spheres and few-walled
carbon nanotubes (FWNTs) linked by the carboxylated conjugated polymer, poly[3
(potassium-4-butanoate) thiophene] (PPBT), was designed to demonstrate benefits
derived from the rational consideration of electron/ion transport coupled with
the surface chemistry of the electrode materials components. To maximize
transport properties, the approach introduces monodispersed spherical Fe3O4
(sFe3O4) for uniform Li+ diffusion and a FWNT web electrode frame that affords
characteristics of long-ranged electronic pathways and porous networks. The
sFe3O4 particles were used as a model high-capacity energy active material, owing
to their well-defined chemistry with surface hydroxyl (-OH) functionalities that
provide for facile detection of molecular interactions. PPBT, having a pi
conjugated backbone and alkyl side chains substituted with carboxylate moieties,
interacted with the FWNT pi-electron-rich and hydroxylated sFe3O4 surfaces, which
enabled the formation of effective electrical bridges between the respective
components, contributing to efficient electron transport and electrode stability.
To further induce interactions between PPBT and the metal hydroxide surface,
polyethylene glycol was coated onto the sFe3O4 particles, allowing for facile
materials dispersion and connectivity. Additionally, the introduction of carbon
particles into the web electrode minimized sFe3O4 aggregation and afforded more
porous FWNT networks. As a consequence, the design of composite electrodes with
rigorous consideration of specific molecular interactions induced by the surface
chemistries favorably influenced electrochemical kinetics and electrode
resistance, which afforded high-performance electrodes for battery applications.
PMID- 29337527
TI - Firefly-like Water Splitting Cells Based on FRET Phenomena with Ultrahigh
Performance over 12.
AB - A firefly-like chemiluminescence reaction was utilized in a ZrO2 nanoparticle
matrix of water splitting cells, where the chlorophyll of Lantana camara was used
as the major photosensitizer to excite electrons to the conduction band of ZrO2.
The fluorescence resonance energy transfer (FRET) was induced by rubrene, a
firefly-like chemiluminescence molecule, and Lantana camara chlorophyll combined
with 9,10-diphenylanthracene. The ZrO2 nanoparticle film coated by the
chlorophyll of Lantana camara and 9,10-diphenylanthracene under chemiluminescence
irradiation in 1 M KHCO3 water solution demonstrated the highest photocurrent
density (88.1 A/m2) and the highest water splitting efficiency (12.77%).
PMID- 29337528
TI - Directed Self-Assembly of Dipeptide Single Crystal in a Capillary.
AB - Controlled growth of one-dimensional nanostructures is playing a key role in
creating types of materials for functional devices. Here, we report procedures
for controlled assembly of the dipeptide diphenylalanine (FF) into aligned and
ultralong single crystals in a capillary. With the evaporation of solvent,
nucleation of the crystal occurred in the confined region, and the crystal grew
continuously with a supply of molecules from the concentration gradient system
inside the capillary. Based on the "Knudsen regime", an ultralong aligned
individual FF single crystal possessing an active optical waveguide property at
macroscopic length scale could be obtained. Moreover, capillary is also an
effective microdevice to investigate the disassembly process of the FF single
crystals. This strategy has potentials to broaden the range of applications of
aligned organic nanomaterials.
PMID- 29337530
TI - Label-Free and Ultrasensitive Biomolecule Detection Based on Aggregation Induced
Emission Fluorogen via Target-Triggered Hemin/G-Quadruplex-Catalyzed Oxidation
Reaction.
AB - Fluorescence biosensing strategy has drawn substantial attention due to their
advantages of simplicity, convenience, sensitivity, and selectivity, but
unsatisfactory structure stability, low fluorescence quantum yield, high cost of
labeling, and strict reaction conditions associated with current fluorescence
methods severely prohibit their potential application. To address these
challenges, we herein propose an ultrasensitive label-free fluorescence biosensor
by integrating hemin/G-quadruplex-catalyzed oxidation reaction with aggregation
induced emission (AIE) fluorogen-based system. l-Cysteine/TPE-M, which is
carefully and elaborately designed and developed, obviously contributes to strong
fluorescence emission. In the presence of G-rich DNA along with K+ and hemin,
efficient destruction of l-cysteine occurs due to hemin/G-quadruplex-catalyzed
oxidation reactions. As a result, highly sensitive fluorescence detection of G
rich DNA is readily realized, with a detection limit down to 33 pM. As a
validation for the further development of the proposed strategy, we also
successfully construct ultrasensitive platforms for microRNA by incorporating the
l-cysteine/TPE-M system with target-triggered cyclic amplification reaction.
Thus, this proposed strategy is anticipated to find use in basic biochemical
research and clinical diagnosis.
PMID- 29337529
TI - Glutathione-Capped Ag2S Nanoclusters Inhibit Coronavirus Proliferation through
Blockage of Viral RNA Synthesis and Budding.
AB - Development of novel antiviral reagents is of great importance for the control of
virus spread. Here, Ag2S nanoclusters (NCs) were proved for the first time to
possess highly efficient antiviral activity by using porcine epidemic diarrhea
virus (PEDV) as a model of coronavirus. Analyses of virus titers showed that Ag2S
NCs significantly suppressed the infection of PEDV by about 3 orders of magnitude
at the noncytotoxic concentration at 12 h postinfection, which was further
confirmed by the expression of viral proteins. Mechanism investigations indicated
that Ag2S NCs treatment inhibits the synthesis of viral negative-strand RNA and
viral budding. Ag2S NCs treatment was also found to positively regulate the
generation of IFN-stimulating genes (ISGs) and the expression of proinflammation
cytokines, which might prevent PEDV infection. This study suggest the novel
underlying of Ag2S NCs as a promising therapeutic drug for coronavirus.
PMID- 29337531
TI - Branched Glycerol-Based Copolymer with Ultrahigh p65 siRNA Delivery Efficiency
for Enhanced Cancer Therapy.
AB - The small interfering RNA (siRNA) is emerging as a potential therapeutic for the
treatment of various diseases because of the targeted gene silencing capability.
The suppression of p65 expression has shown great potential in various cancer
treatments. However, various substantial obstacles limit its clinical
applications, including low cellular uptake, instability, and cytotoxicity of
delivery vehicles. We show a highly branched and biocompatible glycerol-based
copolymer (HBGC) to effectively deliver siRNA for excellent p65 gene silencing
and safe lung cancer treatment in vitro and in vivo. HBGCs could be synthesized
through a facile and modular one-spot Michael addition. HBGCs effectively protect
siRNA in serum, enhance cellular uptake of siRNA, and show negligible
cytotoxicity in various cells (A549, HeLa, HepG2, and C2C12). Additionally, the
HBGC-siRNA complex potently downregulates the p65 expression in A549 cancer cells
(almost the highest value of 96% in reported references) and enhances the
cellular apoptosis compared to that of commercial transfection agents
polyethyleneimine 25 kDa and Lipofectamine 2000. The HBGC-siRNA complex
demonstrated significantly increased accumulation in the tumor sites and enhanced
downregulation of p65 gene and cancer cell apoptosis. Furthermore, the tumor
growth could be significantly inhibited in a subcutaneous lung tumor model with
negligible adverse effects.
PMID- 29337532
TI - Biotemplated Morpho Butterfly Wings for Tunable Structurally Colored
Photocatalysts.
AB - Morpho sulkowskyi butterfly wings contain naturally occurring hierarchical
nanostructures that produce structural coloration. The high aspect ratio and
surface area of these wings make them attractive nanostructured templates for
applications in solar energy and photocatalysis. However, biomimetic approaches
to replicate their complex structural features and integrate functional materials
into their three-dimensional framework are highly limited in precision and
scalability. Herein, a biotemplating approach is presented that precisely
replicates Morpho nanostructures by depositing nanocrystalline ZnO coatings onto
wings via low-temperature atomic layer deposition (ALD). This study demonstrates
the ability to precisely tune the natural structural coloration while also
integrating multifunctionality by imparting photocatalytic activity onto fully
intact Morpho wings. Optical spectroscopy and finite-difference time-domain
numerical modeling demonstrate that ALD ZnO coatings can rationally tune the
structural coloration across the visible spectrum. These structurally colored
photocatalysts exhibit an optimal coating thickness to maximize photocatalytic
activity, which is attributed to trade-offs between light absorption and
catalytic quantum yield with increasing coating thickness. These multifunctional
photocatalysts present a new approach to integrating solar energy harvesting into
visually attractive surfaces that can be integrated into building facades or
other macroscopic structures to impart aesthetic appeal.
PMID- 29337533
TI - Localized Fe(II)-Induced Cytotoxic Reactive Oxygen Species Generating Nanosystem
for Enhanced Anticancer Therapy.
AB - The anticancer therapy on the basis of reactive oxygen species (ROS)-mediated
cellular apoptosis has achieved great progress. However, this kind of theraputic
strategy still faces some challenges such as light, photosensitizer and oxygen
(O2) dependence. In this article, a ROS-mediated anticancer therapy independent
of light, photosensitizer and oxygen was established based on a Fe2+-induced ROS
generating nanosystem. First, artemisinin (ART) was loaded in porous magnetic
supraparticles (MSP) by a nanodeposition method. Then, the poly(aspartic acid)
based polymer, which consisted of dopamine, indocyanine green, and polyethylene
glycol side chain, was coated onto the surface of ART-loaded MSP. When the
nanoparticles entered into cancer cells, a reaction of Fe2+-mediated cleavage of
the endoperoxide bridge contained in ART occurred and subsequent a large amount
of ROS was generated. Moreover, a NIR light was used to effectively increase the
local temperature of tumor in virtue of the superior photothermal effects of MSP,
which enabled us to accelerate the ROS generation and achieved an enhanced ROS
yield. The newly developed nanodrug system displayed a high level of
intracellular ROS generation, leading to the desired killing efficacy against
malignant cells and solid tumor. This smart nanosystem holds great potential to
overcome the existing barrier in PDT and opens a promising avenue for anticancer
therapy.
PMID- 29337534
TI - Highly Luminescent Encapsulated Narrow Bandgap Polymers Based on
Diketopyrrolopyrrole.
AB - We present the synthesis and characterization of a series of encapsulated
diketopyrrolopyrrole red-emitting conjugated polymers. The novel materials
display extremely high fluorescence quantum yields in both solution (>70%) and
thin film (>20%). Both the absorption and emission spectra show clearer, more
defined features compared to their naked counterparts demonstrating the
suppression of inter and intramolecular aggregation. We find that the
encapsulation results in decreased energetic disorder and a dramatic increase in
backbone colinearity as evidenced by scanning tunnelling microscopy. This study
paves the way for diketopyrrolopyrrole to be used in emissive solid state
applications and demonstrates a novel method to reduce structural disorder in
conjugated polymers.
PMID- 29337535
TI - Anion-Mediated Photophysical Behavior in a C60 Fullerene [3]Rotaxane Shuttle.
AB - By addressing the challenge of controlling molecular motion, mechanically
interlocked molecular machines are primed for a variety of applications in the
field of nanotechnology. Specifically, the designed manipulation of communication
pathways between electron donor and acceptor moieties that are strategically
integrated into dynamic photoactive rotaxanes and catenanes may lead to efficient
artificial photosynthetic devices. In this pursuit, a novel [3]rotaxane molecular
shuttle consisting of a four-station bis-naphthalene diimide (NDI) and central
C60 fullerene bis-triazolium axle component and two mechanically bonded
ferrocenyl-functionalized isophthalamide anion binding site-containing
macrocycles is constructed using an anion template synthetic methodology. Dynamic
coconformational anion recognition-mediated shuttling, which alters the relative
positions of the electron donor and acceptor motifs of the [3]rotaxane's
macrocycle and axle components, is demonstrated initially by 1H NMR spectroscopy.
Detailed steady-state and time-resolved UV-vis-IR absorption and emission
spectroscopies as well as electrochemical studies are employed to further probe
the anion-dependent positional macrocycle-axle station state of the molecular
shuttle, revealing a striking on/off switchable emission response induced by
anion binding. Specifically, the [3]rotaxane chloride coconformation, where the
ferrocenyl-functionalized macrocycles reside at the center of the axle component,
precludes electron transfer to NDI, resulting in the switching-on of emission
from the NDI fluorophore and concomitant formation of a C60 fullerene-based
charge-separated state. By stark contrast, in the absence of chloride as the
hexafluorophosphate salt, the ferrocenyl-functionalized macrocycles shuttle to
the peripheral NDI axle stations, quenching the NDI emission via formation of a
NDI-containing charge-separated state. Such anion-mediated control of the
photophysical behavior of a rotaxane through molecular motion is unprecedented.
PMID- 29337536
TI - Correction to "Adaptation in Constitutional Dynamic Libraries and Networks,
Switching between Orthogonal Metalloselection and Photoselection Processes".
PMID- 29337537
TI - Microplastic Effect Thresholds for Freshwater Benthic Macroinvertebrates.
AB - Now that microplastics have been detected in lakes, rivers, and estuaries all
over the globe, evaluating their effects on biota has become an urgent research
priority. This is the first study that aims at determining the effect thresholds
for a battery of six freshwater benthic macroinvertebrates with different species
traits, using a wide range of microplastic concentrations. Standardized 28 days
single species bioassays were performed under environmentally relevant exposure
conditions using polystyrene microplastics (20-500 MUm) mixed with sediment at
concentrations ranging from 0 to 40% sediment dry weight (dw). Microplastics
caused no effects on the survival of Gammarus pulex, Hyalella azteca, Asellus
aquaticus, Sphaerium corneum, and Tubifex spp. and no effects were found on the
reproduction of Lumbriculus variegatus. No significant differences in growth were
found for H. azteca, A. aquaticus, S. corneum, L. variegatus, and Tubifex spp.
However, G. pulex showed a significant reduction in growth (EC10 = 1.07% sediment
dw) and microplastic uptake was proportional with microplastic concentrations in
sediment. These results indicate that although the risks of environmentally
realistic concentrations of microplastics may be low, they still may affect the
biodiversity and the functioning of aquatic communities which after all also
depend on the sensitive species.
PMID- 29337538
TI - Sustainable Polyester Elastomers from Lactones: Synthesis, Properties, and
Enzymatic Hydrolyzability.
AB - Chemically cross-linked elastomers are an important class of polymeric materials
with excellent temperature and solvent resistance. However, nearly all elastomers
are petroleum-derived and persist in the environment or in landfills long after
they are discarded; this work strives to address these issues by demonstrating
the synthesis of renewable, enzymatically hydrolyzable, and mechanically
competitive polyester elastomers. The elastomers described were synthesized using
a novel bis(beta-lactone) cross-linker and star-shaped, hydroxyl-terminated
poly(gamma-methyl-epsilon-caprolactone). Using model compounds, we determined
that the bis(beta-lactone) cross-linker undergoes acyl bond cleavage to afford
beta-hydroxyesters at the junctions. The mechanical properties of the cross
linked materials were tunable and competitive with a commodity rubber band.
Furthermore, the elastomers demonstrated high thermal stability and a low glass
transition (-50 degrees C), indicating a wide range of use temperatures. The
polyester networks were also subjected to enzymatic hydrolysis experiments to
investigate the potential for these materials to biodegrade in natural
environments. We found that they readily hydrolyzed at neutral pH and
environmentally relevant temperatures (2-40 degrees C); complete hydrolysis was
achieved in all cases at temperature-dependent rates. The results presented in
this work exemplify the development of high performance yet sustainable
alternatives to conventional elastomers.
PMID- 29337539
TI - A Comparative IRMPD and DFT Study of Fe3+ and UO22+ Complexation with N
Methylacetohydroxamic Acid.
AB - Iron(III) and uranyl complexes of N-methylacetohydroxamic acid (NMAH) have been
investigated by mass spectrometry, infrared multiphoton dissociation (IRMPD)
spectroscopy, and density functional theory (DFT) calculations. A comparison
between IRMPD and theoretical IR spectra enabled one to probe the structures for
some selected complexes detected in the gas phase. The results show that
coordination of Fe3+ and UO22+ by hydroxamic acid is of a very similar nature.
Natural bond orbital analysis suggests that bonding in uranyl complexes possesses
a slightly stronger ionic character than that in iron complexes. Collision
induced dissociation (CID), IRMPD, and 18O-labeling experiments unambiguously
revealed a rare example of the U?O bond activation concomitant with the
elimination of a water molecule from the gaseous [UO2(NMA)(NMAH)2]+ complex. The
U?O bond activation is observed only for complexes with one monodentate NMAH
molecule forming a hydrogen bond toward one "yl" oxygen atom, as was found by DFT
calculations. This reactivity might explain oxygen exchange observed for uranyl
complexes.
PMID- 29337540
TI - Enhanced Degradation of Pesticide Dichlorophen by Laccase Immobilized on
Nanoporous Materials: A Cytotoxic and Molecular Simulation Investigation.
AB - Use of pesticides is usually related to overproduction of crops in order to
overcome worldwide demand of food and alimentary safety. Nevertheless, pesticides
are environmental persistent molecules, such as the organochlorine pesticides,
which are often found in undesired places. In this work, we show that a hybrid
nanomaterial (laccase-MSU-F) readily oxidizes the pesticide dichlorophen,
reducing its acute genotoxicity and apoptotic effects. In order to predict
chronic alterations related to endocrine disruption, we compared the calculated
affinity of dichlorophen oxidized subproducts to steroid hormone nuclear
receptors (NRs), using molecular simulation methods. We found a reduction in
theoretical affinity of subproducts of oxidized dichlorophen for the ligand
binding pocket of NRs (~5 kcal/mol), likewise of changes in binding modes, that
suggests a reduction in binding events (RMSD values < 10 A).
PMID- 29337541
TI - Enzyme Architecture: The Role of a Flexible Loop in Activation of Glycerol-3
phosphate Dehydrogenase for Catalysis of Hydride Transfer.
AB - The side chain of Q295 of glycerol-3-phosphate dehydrogenase from human liver (
hlGPDH) lies in a flexible loop, that folds over the phosphodianion of substrate
dihydroxyacetone phosphate (DHAP). Q295 interacts with the side-chain cation from
R269, which is ion-paired to the substrate phosphodianion. Kinetic parameters
kcat/ Km (M-1 s-1) and kcat/ KGA KHPi (M-2 s-1) were determined, respectively,
for catalysis of the reduction of DHAP and for dianion activation of catalysis of
reduction of glycolaldehyde (GA) catalyzed by wild-type, Q295G, Q295S, Q295A, and
Q295N mutants of hlGPDH. These mutations result in up to a 150-fold decrease in (
kcat/ Km)DHAP and up to a 2.7 kcal/mol decrease in the intrinsic phosphodianion
binding energy. The data define a linear correlation with slope 1.1, between the
intrinsic phosphodianion binding energy and the intrinsic phosphite dianion
binding energy for activation of hlGPDH-catalyzed reduction of GA, that
demonstrates a role for Q295 in optimizing this dianion binding energy. The R269A
mutation of wild-type GPDH results in a 9.1 kcal/mol destabilization of the
transition state for reduction of DHAP, but the same R269A mutation of N270A and
Q295A mutants result in smaller 5.9 and 4.9 kcal/mol transition-state
destabilization. Similarly, the N270A or Q295A mutations of R269A GPDH each
result in large falloffs in the efficiency of rescue of the R269A mutant by
guanidine cation. We conclude that N270, which interacts for the substrate
phosphodianion and Q295, which interacts with the guanidine side chain of R269,
function to optimize the apparent transition-state stabilization provided by the
cationic side chain of R269.
PMID- 29337542
TI - A Domino Process toward Functionally Dense Quaternary Carbons through Pd
Catalyzed Decarboxylative C(sp3)-C(sp3) Bond Formation.
AB - An efficient protocol was developed to construct functionally dense quaternary
carbons with concomitant formation of a new Csp3-Csp3 bond via Pd-catalyzed
decarboxylative transformation of vinyl cyclic carbonates. This redox-neutral
catalytic system features stereocontrolled formation of multisubstituted allylic
scaffolds with an aldehyde functionality generated in situ, and it typically can
be performed at room temperature without any additives. DFT calculations provide
a rationale toward the selective formation of these compounds and reveal a
complex mechanism that with the help of microkinetic models is able to reproduce
the nontrivial dependence of the identity of the product on the nature of the
substituents in the substrate.
PMID- 29337544
TI - Pushing up the Size Limit of Metal Chalcogenide Supertetrahedral Nanocluster.
AB - The cubic ZnS structure type and the size-dependent properties of related
nanoparticles are of both fundamental and technological importance. Yet, it
remains a challenge to synthesize large atom-precise clusters of this structure
type. Currently, only supertetrahedral clusters with 4, 10, 20, and 35 metal
sites (denoted as T2, T3, T4, and T5, respectively) are known. Because the
synthesis of T5 in 2002, numerous synthetic efforts targeting larger clusters
only resulted in T2-T5 clusters in various compositions and intercluster
connectivity, with T6 (56 metal and 84 anion sites) being elusive. Here, we
report the so-far largest supertetrahedral cluster (T6, [Zn25In31S84]25-). New T6
clusters can serve as the host matrix for optically active centers. Mn-doped
variants of T4 and T6 have also been made, allowing the investigation of site
dependent Mn emission. The results lead to the elucidation of the mechanism
regulating Mn emission via size-dependent crystal lattice strain and provide new
insight into Mn-doping chemistry in cluster-based chalcogenides at the atomic
level.
PMID- 29337545
TI - Donor Engineering for NIR-II Molecular Fluorophores with Enhanced Fluorescent
Performance.
AB - Organic fluorophores have been widely used for biological imaging in the visible
and the first near-infrared windows. However, their application in the second
near-infrared window (NIR-II, 1000-1700 nm) is still limited mainly due to low
fluorescence quantum yields (QYs). Here, we explore molecular engineering on the
donor unit to develop high performance NIR-II fluorophores. The fluorophores are
constructed by a shielding unit-donor(s)-acceptor-donor(s)-shielding unit
structure. Thiophene is introduced as the second donor connected to the shielding
unit, which can increase the conjugation length and red-shift the fluorescence
emission. Alkyl thiophene is employed as the first donor connected to the
acceptor unit. The bulky and hydrophobic alkyl thiophene donor affords larger
distortion of the conjugated backbone and fewer interactions with water molecules
compared to other donor units studied before. The molecular fluorophore IR-FTAP
with octyl thiophene as the first donor and thiophene as the second donor
exhibits fluorescence emission peaked at 1048 nm with a QY of 5.3% in aqueous
solutions, one of the highest for molecular NIR-II fluorophore reported so far.
Superior temporal and spatial resolutions have been demonstrated with IR-FTAP
fluorophore for NIR-II imaging of the blood vessels of a mouse hindlimb.
PMID- 29337547
TI - Calix[n]arene-Catalyzed Three-Component Povarov Reaction: Microwave-Assisted
Synthesis of Julolidines and Mechanistic Insights.
AB - A new one-pot cascade reaction-based application of Povarov reactions with a p
sulfonic acid calix[4]arene catalyst for the synthesis of a series of 34
julolidine derivatives with substituents at C8 or C9 in good to excellent yields
is reported. These microwave-assisted reactions proceeded efficiently, had short
reaction times, were metal-free, were low cost, and used an inexpensive, easily
available and nontoxic catalyst. These advantages, along with a simple workup
procedure, make this protocol a very efficient and green alternative to the
traditional methods for constructing these types of N-heterocyclic skeletons. In
addition, this protocol allows the formation of julolidine structures, which
requires the construction of four new C-C bonds and two C-N bonds. A mechanism
for the Povarov reaction involving a stepwise sequence via ionic intermediates
was proposed and validated.
PMID- 29337543
TI - Bright Side of Lignin Depolymerization: Toward New Platform Chemicals.
AB - Lignin, a major component of lignocellulose, is the largest source of aromatic
building blocks on the planet and harbors great potential to serve as starting
material for the production of biobased products. Despite the initial challenges
associated with the robust and irregular structure of lignin, the valorization of
this intriguing aromatic biopolymer has come a long way: recently, many creative
strategies emerged that deliver defined products via catalytic or biocatalytic
depolymerization in good yields. The purpose of this review is to provide insight
into these novel approaches and the potential application of such emerging new
structures for the synthesis of biobased polymers or pharmacologically active
molecules. Existing strategies for functionalization or defunctionalization of
lignin-based compounds are also summarized. Following the whole value chain from
raw lignocellulose through depolymerization to application whenever possible,
specific lignin-based compounds emerge that could be in the future considered as
potential lignin-derived platform chemicals.
PMID- 29337546
TI - A Mitochondria-Specific Fluorescent Probe for Visualizing Endogenous Hydrogen
Cyanide Fluctuations in Neurons.
AB - An ability to visualize HCN in mitochondria in real time may permit additional
insights into the critical toxicological and physiological roles this classic
toxin plays in living organisms. Herein, we report a mitochondria-specific
coumarin pyrrolidinium-derived fluorescence probe (MRP1) that permits the real
time ratiometric imaging of HCN in living cells. The response is specific,
sensitive (detection limit is ca. 65.6 nM), rapid (within 1 s), and reversible.
Probe MRP1 contains a benzyl chloride subunit designed to enhance retention
within the mitochondria under conditions where the mitochondria membrane
potential is eliminated. It has proved effective in visualizing different
concentrations of exogenous HCN in the mitochondria of HepG2 cells, as well as
the imaging of endogenous HCN in the mitochondria of PC12 cells and within
neurons. Fluctuations in HCN levels arising from the intracellular generation of
HCN could be readily detected.
PMID- 29337548
TI - RE[N(SiMe3)2]3-Catalyzed Guanylation/Cyclization of Amino Acid Esters and
Carbodiimides.
AB - The example of rare-earth metal-catalyzed guanylation/cyclization of amino acid
esters and carbodiimides is well-established, forming 4(3H)-2
alkylaminoquinazolinones in 65-96% yields. The rare-earth metal amides
RE[N(TMS)2]3 (RE = Y, Yb, Nd, Sm, La; TMS = SiMe3) showed high activities, and
La[N(TMS)2]3 performed best for a wide scope of the substrates.
PMID- 29337549
TI - Increasing the Ambient Pressure Solubility by Forming a Glass at High Pressure
and Its Thermodynamics, a Much Sought-After Pharmaceutical Advantage.
AB - With the objective of increasing the bioavailability of poorly soluble curative
compounds, we describe a thermodynamics-based method for increasing their
solubility, sigma. It requires forming their pressure-densified glassy (PDG)
state by supercooling the melt under a high pressure to form glass,
depressurizing, and recovering the glass at a low temperature. First, we formally
show that the excess free energy of PDG is higher at ambient pressure than that
of a glass (normally) formed by supercooling the melt at ambient pressure (NG),
and therefore its sigma will be higher. For a given compound, sigma would
increase with the pressure under which the liquid is cooled to form PDG and also
with increase in the cooling rate. Second, we propose that this increase may be
determined by using differential scanning calorimetry heating scans and, more
accurately and directly, by vapor pressure measurement. Analysis of calorimetry
data of poly(styrene) shows that the magnitude of increase in sigma is
considerable and is expected to be much higher for curative compounds. Since
sigma is related to vapor pressure through the free energy change, and to the
dissolution rate, Gamma, the PDG state a compound would not only sublimate
rapidly but also dissolve rapidly. We discuss the stability of PDG relative to NG
against structural relaxation and crystallization and, hence, of their
bioavailability with time.
PMID- 29337550
TI - Palladium-Catalyzed Oxidative Cross-Coupling of Arylhydrazines and Arenethiols
with Molecular Oxygen as the Sole Oxidant.
AB - A highly efficient palladium-catalyzed oxidative cross-coupling of arylhydrazines
and arenethiols with molecular oxygen as the sole oxidant to afford unsymmetrical
diaryl sulfides has been developed. The only byproducts are nitrogen and water. A
broad range of functional groups, even the reactive iodides, are tolerated and
thus offer the opportunity for further functionalization.
PMID- 29337551
TI - Synthesis of Polycyclic delta-Lactams with Bridged Benzomorphan Skeleton:
Selectivity and Diversity Driven by Substituents.
AB - An efficient synthesis of bromofunctionalized 2,6-methano- and 1,5-methano
benzomorphanones, starting from easily available 6-benzyl-3,6-dihydropyridin
2(1H)-ones, is described. Furthermore, the synthesis of bridged benzomorphanones
with hitherto not known polycyclic systems containing 2- or 3
azabicyclo[4.1.0]heptane units is developed upon treatment of both 2,6- and 1,5
methanobromobenzomorphans with t-BuOK. The effects of substituents on the
diversity and stereoselectivity of both transformations are studied.
PMID- 29337552
TI - Molecular Dynamics Simulations of the Oil-Detachment from the Hydroxylated Silica
Surface: Effects of Surfactants, Electrostatic Interactions, and Water Flows on
the Water Molecular Channel Formation.
AB - The detachment process of an oil molecular layer situated above a horizontal
substrate was often described by a three-stage process. In this mechanism, the
penetration and diffusion of water molecules between the oil phase and the
substrate was proposed to be a crucial step to aid in removal of oil layer/drops
from substrate. In this work, the detachment process of a two-dimensional alkane
molecule layer from a silica surface in aqueous surfactant solutions is studied
by means of molecular dynamics (MD) simulations. By tuning the polarity of model
silica surfaces, as well as considering the different types of surfactant
molecules and the water flow effects, more details about the formation of water
molecular channel and the expansion processes are elucidated. It is found that
for both ionic and nonionic type surfactant solutions, the perturbation of
surfactant molecules on the two-dimensional oil molecule layer facilitates the
injection and diffusion of water molecules between the oil layer and silica
substrate. However, the water channel formation and expansion speed is strongly
affected by the substrate polarity and properties of surfactant molecules. First,
only for the silica surface with relative stronger polarity, the formation of
water molecular channel is observed. Second, the expansion speed of the water
molecular channel upon the ionic surfactant (dodecyl trimethylammonium bromide,
DTAB and sodium dodecyl benzenesulfonate, SDBS) flooding is more rapidly than the
nonionic surfactant system (octylphenol polyoxyethylene(10) ether, OP-10). Third,
the water flow speed may also affect the injection and diffusion of water
molecules. These simulation results indicate that the water molecular channel
formation process is affected by multiple factors. The synergistic effects of
perturbation of surfactant molecules and the electrostatic interactions between
silica substrate and water molecules are two key factors aiding in the injection
and diffusion of water molecules and helpful for the oil detachment from silica
substrate.
PMID- 29337553
TI - Selective Construction of 2-Substituted Benzothiazoles from o-Iodoaniline
Derivatives S8 and N-Tosylhydrazones.
AB - Selective construction of 2-substituted benzothiazoles from o-iodoaniline
derivatives S8 and N-tosylhydrazone via a copper-promoted [3 + 1 + 1]-type
cyclization reaction has been realized. In the protocol, the carbon atom on N
tosylhydrazone could be regulated to construct benzothiazole by changing the
reaction system. Furthermore, the transformation has achieved the construction of
multiple carbon-heteroatom bonds.
PMID- 29337554
TI - Light-Induced Deformation of Azobenzene-Containing Colloidal Spheres: Calculation
and Measurement of Opto-Mechanical Stresses.
AB - We report on light-induced deformation of colloidal spheres consisting of
azobenzene-containing polymers. The colloids of the size between 60 nm and 2 MUm
in diameter were drop casted on a glass surface and irradiated with linearly
polarized light. It was found that colloidal particles can be deformed up to ca.
6 times of their initial diameter. The maximum degree of deformation depends on
the irradiation wavelength and intensity, as well as on colloidal particles size.
On the basis of recently proposed theory by Toshchevikov et al. [ J. Phys. Chem.
Lett. 2017 , 8 , 1094 ], we calculated the opto-mechanical stresses (ca. 100 MPa)
needed for such giant deformations and compared them with the experimental
results.
PMID- 29337555
TI - Reconsideration of the Detection and Fluorescence Mechanism of a Pyrene-Based
Chemosensor for TNT.
AB - The rapid detection of chemical explosives is crucial for national security and
public safety, and the investigation of sensing mechanisms is important for
designing highly efficient chemosensors. This study theoretically investigates
the detection and fluorescence mechanism of a newly synthesized pyrene-based
chemosensor for the detection of trinitrotoluene (TNT) through density-functional
theory (DFT) and time-dependent density-functional-theory (TDDFT) methods and
suggests a different interaction product of the probe and TNT from previously
reported ones [ Mosca et al. J. Am. Chem. Soc. 2015 , 137 , 7967 ]. Instead of
forming Meisenheimer complexes, the energies of which are beyond those of the
reactants, a low-energy product generated by a pi-pi-stacking interaction is more
rational and favorable. The fluorescence-quenching property further confirms that
the pi-pi-stacking product is the predicted one rather than luminescent
Meisenheimer complexes. Frontier-molecular-orbital (FMO)-analysis results show
that photoinduced electron transfer (PET) is the mechanism underlying the
luminescence quenching of the probe upon exposure to TNT.
PMID- 29337556
TI - Organocatalyzed Asymmetric Vinylogous Addition of Oxazole-2(3H)-thiones to
alpha,beta-Unsaturated Ketones: An Additive-Free Approach for Diversification of
Heterocyclic Scaffold.
AB - A straightforward organocatalyzed asymmetric addition of oxazole-2(3H)-thiones to
alpha,beta-unsaturated ketones is described. This additive-free Michael reaction
in the presence of chiral cinchonine-derived primary amines as catalysts has
proven to be highly effective for a wide range of cyclic and acyclic enones,
leading to the Michael adducts in very good yields and excellent
enantioselectivities. The absolute configuration (R) of compound 5j was
unambiguously assigned by X-ray diffraction analysis. Furthermore, experimental
and theoretical studies were performed and a mechanism is presented and discussed
for this novel reaction.
PMID- 29337557
TI - Pair Interaction Energy Decomposition Analysis for Density Functional Theory and
Density-Functional Tight-Binding with an Evaluation of Energy Fluctuations in
Molecular Dynamics.
AB - Pair interaction energy decomposition analysis in the fragment molecular orbital
(FMO) method is extended to treat density functional theory (DFT) and density
functional tight-binding (DFTB). Fluctuations of energy contributions are
obtained from molecular dynamics simulations. Interactions at the DFT and DFTB
levels are compared to the values obtained with Hartree-Fock, second-order Moller
Plesset (MP2), and coupled cluster methods. Hydrogen bonding in water clusters is
analyzed. 200 ps NVT molecular dynamics simulations are performed with FMO for
two ligands bound to the Trp-cage miniprotein (PDB 1L2Y ); the fluctuations of
fragment energies and interactions are analyzed.
PMID- 29337558
TI - Spatial Isolation of Conformational Isomers of Hydroquinone and Its Water Cluster
Using the Stark Deflector.
AB - Conformational isomers of hydroquinone and their 1:1 clusters with water have
been spatially separated using a Stark deflector in a supersonic jet. trans
Hydroquinone (HyQ) conformer with zero dipole moment is little influenced by
inhomogeneous electric fields, whereas cis conformer with nonzero dipole moment
(2.38 D) is significantly deflected from the molecular beam axis into the
direction along which the strong field gradient is applied. Resonant two photon
ionization carried out by shifting the laser position perpendicular to the
molecular beam axis after the Stark deflector then gives an exclusive S1-S0
excitation spectrum of the cis conformer only, making possible immaculate
conformer-specific spectroscopy and dynamics. As the spatial separation is
apparently proportional to the effective dipole moment strength, conformational
assignment could be absolute in the Stark deflector, which contrasts with the
hole-burning spectroscopic technique where identification of a conformational
isomer is intrinsically not unambiguous. trans- and cis-HyQ-H2O clusters have
also been spatially separated according to their distinct effective dipole moment
strengths to give absolute spectroscopic identification of each cluster isomer,
nailing down the otherwise disputable conformational assignment. This is the
first report for the spatial separation of conformational cluster isomers.
PMID- 29337559
TI - Totally Organic Redox-Active pH-Sensitive Nanoparticles Stabilized by Amphiphilic
Aromatic Polyketones.
AB - Amphiphilic aromatic polymers have been synthesized by grafting aliphatic
polyketones with 4-(aminomethyl)benzoic acid at different molar ratios via the
Paal-Knorr reaction. The resulting polymers, showing diketone conversion degree
of 16%, 37%, 53%, and 69%, have been complexed with the redox-active 2,3,5
triphenyl-2H-tetrazolium chloride, a precursor molecule with which aromatic
aromatic interactions are held. Upon addition of ascorbic acid to the complexes,
in situ reduction of the tetrazolium salt produced 1,3,5-triphenylformazan
nanoparticles stabilized by the amphiphilic polymers. The stabilized
nanoparticles display highly negative zeta potential [-(35-70) mV] and
hydrodynamic diameters in the submicron range (100-400 nm). Nonaromatic
polyelectrolytes or hydrophilic aromatic copolymers showing low linear aromatic
density and high linear charge density such as acrylate/maleate and
sulfonate/maleate-containing polymers were unable to stabilize formazan
nanoparticles synthesized by the same method. The copolymers studied here bear
uncharged nonaromatic comonomers (unreacted diketone units) as well as charged
aromatic comonomers, which furnish amphiphilia. Thus, the linear aromatic density
and the maximum linear charge density have the same value for each copolymer, and
the hydrophilic/hydrophobic balance varies with the diketone conversion degree.
The amphiphilia of the copolymers allows the stabilization of the nanoparticles,
even with the copolymers showing a low linear aromatic density. The method of
nanoparticle synthesis constitutes a simple, cheap, and green method for the
production of switchable totally organic, redox-active, pH-sensitive
nanoparticles that can be reversibly turned into macroprecipitates upon pH
changing.
PMID- 29337560
TI - Visible Light-Promoted Three-Component Tandem Annulation for the Synthesis of 2
Iminothiazolidin-4-ones.
AB - Described is a visible light-promoted three-component tandem annulation of
amines, aryl/alkyl isothiocyanates, and alpha-bromoesters to form 2
iminothiazolidin-4-ones in the absence of metal and photocatalyst at room
temperature. This [1 + 2 + 2] cyclization strategy involves visible light
promoted C-S/C-N bond formation and features a powerful approach to the synthesis
of 2-iminothiazolidin-4-ones with broad substrate scope, excellent functional
group tolerance, mild reaction conditions, step-economy, and simple operation,
which also has potential applications in the pharmaceutical industry. UV-vis
spectroscopy indicates that an in situ-generated H-bonding electron donor
acceptor (EDA) complex probably acts as the photocatalyst, facilitating the
reaction process.
PMID- 29337561
TI - Methylammonium Cation Dynamics in Methylammonium Lead Halide Perovskites: A Solid
State NMR Perspective.
AB - In light of the intense recent interest in the methylammonium lead halides,
CH3NH3PbX3 (X = Cl, Br, and I) as sensitizers for photovoltaic cells, the
dynamics of the methylammonium (MA) cation in these perovskite salts has been
reinvestigated as a function of temperature via 2H, 14N, and 207Pb NMR
spectroscopy. In the cubic phase of all three salts, the MA cation undergoes
pseudoisotropic tumbling (picosecond time scale). For example, the correlation
time, tau2, for the C-N axis of the iodide salt is 0.85 +/- 0.30 ps at 330 K. The
dynamics of the MA cation are essentially continuous across the cubic <->
tetragonal phase transition; however, 2H and 14N NMR line shapes indicate that
subtle ordering of the MA cation occurs in the tetragonal phase. The temperature
dependence of the cation ordering is rationalized using a six-site model, with
two equivalent sites along the c-axis and four equivalent sites either
perpendicular or approximately perpendicular to this axis. As the cubic <->
tetragonal phase transition temperature is approached, the six sites are nearly
equally populated. Below the tetragonal <-> orthorhombic phase transition, 2H NMR
line shapes indicate that the C-N axis is essentially frozen.
PMID- 29337562
TI - Physiologically Based Pharmacokinetic Modeling in Lead Optimization. 2. Rational
Bioavailability Design by Global Sensitivity Analysis To Identify Properties
Affecting Bioavailability.
AB - When medicinal chemists need to improve oral bioavailability (%F) during lead
optimization, they systematically modify compound properties mainly based on
their own experience and general rules of thumb. However, at least a dozen
properties can influence %F, and the difficulty of multiparameter optimization
for such complex nonlinear processes grows combinatorially with the number of
variables. Furthermore, strategies can be in conflict. For example, adding a
polar or charged group will generally increase solubility but decrease
permeability. Identifying the 2 or 3 properties that most influence %F for a
given compound series would make %F optimization much more efficient. We
previously reported an adaptation of physiologically based pharmacokinetic (PBPK)
simulations to predict %F for lead series from purely computational inputs within
a 2-fold average error. Here, we run thousands of such simulations to generate a
comprehensive "bioavailability landscape" for each series. A key innovation was
recognition that the large and variable number of p Ka's in drug molecules could
be replaced by just the two straddling the isoelectric point. Another was use of
the ZINC database to cull out chemically inaccessible regions of property space.
A quadratic partial least squares regression (PLS) accurately fits a continuous
surface to these thousands of bioavailability predictions. The PLS coefficients
indicate the globally sensitive compound properties. The PLS surface also
displays the %F landscape in these sensitive properties locally around compounds
of particular interest. Finally, being quick to calculate, the PLS equation can
be combined with models for activity and other properties for multiobjective lead
optimization.
PMID- 29337563
TI - Magic-Angle Stacking and Strong Intermolecular pi-pi Interaction in a Perylene
Bisimide Crystal: An Approach for Efficient Near-Infrared (NIR) Emission and High
Electron Mobility.
AB - A single crystal of N,N'-bis(4-methoxybenzyl)perylene-3,4,9,10-bis(dicarboximide)
(mb-PBI) that possesses novel magic-angle stacking (M-type stacking) and strong
intermolecular pi-pi interaction is achieved by physical vapor transport (PVT),
which shows attractive optoelectronic functions such as efficient NIR emission
and high electron mobility. In this special M-type staking, the strong Frenkel/CT
mixing state promotes fluorescence and, importantly, the elimination of long
distance Forster resonance energy transfer enables the minimization of the
possible fluorescence quenching, which ensure the highly efficient emission.
Moreover, the strong pi-pi interaction elongates the "supramolecular conjugation"
to reduce the energy gap and also benefits the electron mobility of the crystal.
The experimental results clearly indicate that M-type staking is a novel approach
to optimize the optoelectronic functions of organic semiconducting materials.
PMID- 29337564
TI - Vibrational Dynamics and Couplings of the Hydrated RNA Backbone: A Two
Dimensional Infrared Study.
AB - The equilibrium structure of the RNA sugar-phosphate backbone and its hydration
shell is distinctly different from hydrated DNA. Applying femtosecond two
dimensional infrared (2D-IR) spectroscopy in a range from 950 to 1300 cm-1, we
elucidate the character, dynamics, and couplings of backbone modes of a double
stranded RNA A-helix geometry in its aqueous environment. The 2D-IR spectra
display a greater number of backbone modes than for DNA, with distinctly
different lineshapes of diagonal peaks. Phosphate-ribose interactions and local
hydration structures are reflected in the complex coupling pattern of RNA modes.
Interactions with the fluctuating water shell give rise to spectral diffusion on
a 300 fs time scale, leading to a quasi-homogeneous line shape of the symmetric
(PO2)- stretching mode of the strongly hydrated phosphate groups. The RNA results
are benchmarked by 2D-IR spectra of DNA oligomers in water and analyzed by
molecular dynamics and quantum mechanical molecular mechanics simulations.
PMID- 29337565
TI - Quantum Control of Graphene Plasmon Excitation and Propagation at Heaviside
Potential Steps.
AB - Quantum mechanical effects of single particles can affect the collective plasmon
behaviors substantially. In this work, the quantum control of plasmon excitation
and propagation in graphene is demonstrated by adopting the variable quantum
transmission of carriers at Heaviside potential steps as a tuning knob. First,
the plasmon reflection is revealed to be tunable within a broad range by varying
the ratio gamma between the carrier energy and potential height, which originates
from the quantum mechanical effect of carrier propagation at potential steps.
Moreover, the plasmon excitation by free-space photos can be regulated from fully
suppressed to fully launched in graphene potential wells also through adjusting
gamma, which defines the degrees of the carrier confinement in the potential
wells. These discovered quantum plasmon effects offer a unified quantum
mechanical solution toward ultimate control of both plasmon launching and
propagating, which are indispensable processes in building plasmon circuitry.
PMID- 29337566
TI - Cationic Polymeric Nanoparticle Delivering CCR2 siRNA to Inflammatory Monocytes
for Tumor Microenvironment Modification and Cancer Therapy.
AB - Accumulating evidence has confirmed that malignant tumors have a complex
microenvironment, which consists of a heterogeneous collection of tumor cells and
other cell subsets (including the full gamut of immune cells). Tumor-associated
macrophages (TAMs), derived from circulating Ly6Chi monocytes, constitute the
most substantial fraction of tumor-infiltrating immune cells in nearly all cancer
types and contribute to tumor progression, vascularization, metastasis,
immunosuppression, and therapeutic resistance. Interrupting monocyte recruitment
to tumor tissues by disturbing pivotal signaling pathways (such as CCL2-CCR2) is
viewed as one of the most promising avenues for tumor microenvironment
manipulation and cancer therapy. One critical issue for monocyte-based therapy is
to deliver therapeutic agents into monocytes efficiently. In the present study,
we systematically investigated the relationship between the surface potential and
the biodistribution of polymeric nanoparticles in monocytes in vivo, aiming to
screen and identify an appropriate delivery system for monocyte targeting, and we
found that cationic nanoparticles have a higher propensity to accumulate in
monocytes compared with their neutral counterparts. We further demonstrated that
siCCR2-encapsulated cationic nanoparticle (CNP/siCCR2) could modify
immunosuppressive tumor microenvironment more efficiently and exhibit superior
antitumor effect in an orthotopic murine breast cancer model.
PMID- 29337567
TI - Ultrafast Graphene Light Emitters.
AB - Ultrafast electrically driven nanoscale light sources are critical components in
nanophotonics. Compound semiconductor-based light sources for the nanophotonic
platforms have been extensively investigated over the past decades. However,
monolithic ultrafast light sources with a small footprint remain a challenge.
Here, we demonstrate electrically driven ultrafast graphene light emitters that
achieve light pulse generation with up to 10 GHz bandwidth across a broad
spectral range from the visible to the near-infrared. The fast response results
from ultrafast charge-carrier dynamics in graphene and weak electron-acoustic
phonon-mediated coupling between the electronic and lattice degrees of freedom.
We also find that encapsulating graphene with hexagonal boron nitride (hBN)
layers strongly modifies the emission spectrum by changing the local optical
density of states, thus providing up to 460% enhancement compared to the gray
body thermal radiation for a broad peak centered at 720 nm. Furthermore, the hBN
encapsulation layers permit stable and bright visible thermal radiation with
electronic temperatures up to 2000 K under ambient conditions as well as
efficient ultrafast electronic cooling via near-field coupling to hybrid
polaritonic modes under electrical excitation. These high-speed graphene light
emitters provide a promising path for on-chip light sources for optical
communications and other optoelectronic applications.
PMID- 29337568
TI - Rational Design of a Green-Light-Mediated Unimolecular Platform for Fast
Switchable Acidic Sensing.
AB - A controllable sensing ability strongly connects to complex and precise events in
diagnosis and treatment. However, imposing visible light into the molecular-scale
mediation of sensing processes is restricted by the lack of structural relevance.
To address this critical challenge, we present the rational design, synthesis,
and in vitro studies of a novel cyanostyryl-modified azulene system for green
light-mediated fast switchable acidic sensing. The advantageous features of the
design include a highly efficient green-light-driven Z/E-isomerization (a quantum
yield up to 61.3%) for fast erasing chromatic and luminescent expressions and a
superior compatibility with control of ratiometric protonation. Significantly,
these merits of the design enable the development of a microfluidic system to
perform a green-light-mediated reusable sensing function toward a gastric acid
analyte in a miniaturized platform. The results may provide new insights for
building future integrated green materials.
PMID- 29337569
TI - Total Synthesis of the Highly N-Methylated Acetylene-Containing Anticancer
Peptide Jahanyne.
AB - The first total synthesis of the highly N-methylated acetylene-containing
lipopeptide jahanyne, an apoptosis-inducing natural product from marine
cyanobacteria, is reported. A late-stage solution-phase coupling enabled
introduction of the C-terminal ketone pyrrolidine moiety. A modified Fmoc solid
phase synthesis strategy was adopted to effectively couple multiple sterically
hindered N-methylated amino acids while suppressing epimerization. The total
synthesis has enabled confirmation of the proposed absolute configuration of
natural jahanyne.
PMID- 29337570
TI - Self-Organization of Metal Nanoparticles in Light: Electrodynamics-Molecular
Dynamics Simulations and Optical Binding Experiments.
AB - Light-driven self-organization of metal nanoparticles (NPs) can lead to unique
optical matter systems, yet simulation of such self-organization (i.e., optical
binding) is a complex computational problem that increases nonlinearly with
system size. Here we show that a combined electrodynamics-molecular dynamics
simulation technique can simulate the trajectories and predict stable
configurations of silver NPs in optical fields. The simulated dynamic equilibrium
of a two-NP system matches the probability density of oscillations for two
optically bound NPs obtained experimentally. The predicted stable configurations
for up to eight NPs are further compared to experimental observations of silver
NP clusters formed by optical binding in a Bessel beam. All configurations are
confirmed to form in real systems, including pentagonal clusters with five-fold
symmetry. Our combined simulations and experiments have revealed a diverse
optical matter system formed by anisotropic optical binding interactions,
providing a new strategy to discover artificial materials.
PMID- 29337571
TI - Direct Observation of a Transiently Formed Isomer During Iodoform Photolysis in
Solution by Time-Resolved X-ray Liquidography.
AB - Photolysis of iodoform (CHI3) in solution has been extensively studied, but its
reaction mechanism remains elusive. In particular, iso-iodoform (iso-CHI2-I) is
formed as a product of the photolysis reaction, but its detailed structure is not
known, and whether it is a major intermediate species has been controversial.
Here, by using time-resolved X-ray liquidography, we determined the reaction
mechanism of CHI3 photodissociation in cyclohexane as well as the structure of
iso-CHI2-I. Both iso-CHI2-I and CHI2 radical were found to be formed within 100
ps with a branching ratio of 40:60. Iodine radicals (I), formed during the course
of CHI3 photolysis, recombine nongeminately with either CHI2 or I. Based on our
structural analysis, the I-I distance and the C-I-I angle of iso-CHI2-I were
determined to be 2.922 +/- 0.004 A and 133.9 +/- 0.8 degrees , respectively.
PMID- 29337572
TI - Plasmonic Horizon in Gold Nanosponges.
AB - An electromagnetic wave impinging on a gold nanosponge coherently excites many
electromagnetic hot-spots inside the nanosponge, yielding a polarization
dependent scattering spectrum. In contrast, a hole, recombining with an electron,
can locally excite plasmonic hot-spots only within a horizon given by the
lifetime of localized plasmons and the speed carrying the information that a
plasmon has been created. This horizon is about 57 nm, decreasing with increasing
size of the nanosponge. Consequently, photoluminescence from large gold
nanosponges appears unpolarized.
PMID- 29337573
TI - Cryoprotectants Severely Exacerbate X-ray-Induced Photoreduction.
AB - Approximately 11% of enzymes contain a transition metal ion that is essential for
catalytic function. Such metalloenzymes catalyze much of the most chemically
challenging and biologically essential chemistry carried out by life. X-ray-based
methods, predominantly macromolecular crystallography (MX) and also X-ray
absorption spectroscopy (XAS), have proved essential for determining structures
of transition metal ion-containing active sites in order to deduce enzyme
catalytic mechanisms. However, X-ray irradiation can induce change in both the
oxidation state and structure of the metal, which is problematic in structure
determination. We present an XAS study of whether cryoprotectants such as
polyethylene glycol (PEG) or glycerol, routinely added to MX or XAS samples to
improve data quality, affect photoreduction. Our data demonstrate a remarkable 10
fold exacerbation in rate of photoreduction of Cu(II) to Cu(I) when alcohol or
ether cryoprotectants are present. Our results suggest that widespread use of
cryoprotectants may increase the potential for erroneous structures.
PMID- 29337574
TI - Singlet Fission Mediated Photophysics of BODIPY Dimers.
AB - The photodynamics of an orthogonal BODIPY dimer, particularly the formation of
triplet states, has been explored by femtosecond and nanosecond transient
absorption measurements. The short time scale data show the appearance of
transient features of triplet character that, according to quantitative analysis
of their intensities, account for more than 100% of the initially excited
molecules, which reveals the occurrence of a singlet fission process in the
isolated dimers. The formation rate of the triplet correlated state 1(TT) is
found to depend on the solvent polarity, pointing to the mediation of a charge
transfer character state. The dissociation of the 1(TT) state into pairs of
individual triplets determines the triplet yield measured in the long time
scales. The kinetic model derived from the results provides a comprehensive view
of the photodynamics of BODIPY dimers and permits rationalization of the
photophysical parameters of these systems.
PMID- 29337575
TI - Optical Signatures of Impurity-Impurity Interactions in Copper Containing II-VI
Alloy Semiconductors.
AB - We study the optical properties of copper containing II-VI alloy quantum dots
(CuxZnyCd1-x-ySe). Copper mole fractions within the host are varied from 0.001 to
0.35. No impurity phases are observed over this composition range, and the
formation of secondary phases of copper selenide are observed only at xCu > 0.45.
The optical absorption and emission spectra of these materials are observed to be
a strong function of xCu, and provide information regarding composition induced
impurity-impurity interactions. In particular, the integrated cross section of
optical absorption per copper atom changes sharply (from 1 * 10 -2 nm3 to 4 * 10
2 nm3) at xCu = 0.12, suggesting a composition induced change in local electronic
structure. These materials may serve as model systems to understand the
electronic structure of I-III-VI2 semiconductor compounds.
PMID- 29337576
TI - Impact of Nanoporosity on Hydrocarbon Transport in Shales' Organic Matter.
AB - In a context of growing attention for shale gas, the precise impact of organic
matter (kerogen) on hydrocarbon recovery from unconventional reservoirs still has
to be assessed. Kerogen's microstructure is characterized by a very disordered
pore network that greatly affects hydrocarbon transport. The specific structure
and texture of this organic matter at the nanoscale is highly dependent on its
origin. In this study, by the use of statistical physics and molecular dynamics,
we shed some new lights on hydrocarbon transport through realistic molecular
models of kerogen at different level of maturity [ Bousige et al. Nat. Mater.
2016 , 15 , 576 ]. Despite the apparent complexity, severe confinement effects
controlled by the porosity of the various kerogens allow linear alkanes (from
methane to dodecane) transport to be studied only via the self-diffusion
coefficients of the species. The decrease of the transport coefficients with the
amount of adsorbed fluid can be described by a free volume theory. Ultimately,
the transport coefficients of hydrocarbons can be expressed simply as a function
of the porosity (volume fraction of void) of the microstructure, thus paving the
way for shale gas recovery predictions.
PMID- 29337577
TI - Preparation of Nano Au and Pt Alloy Microspheres Decorated with Reduced Graphene
Oxide for Nonenzymatic Hydrogen Peroxide Sensing.
AB - The flourish of nanotechnology has brought new vitality to the research and
development of electrochemical sensing materials. In this work, we successfully
synthesized Nano Au and Pt alloy microspheres decorated with reduced graphene
oxide (RGO/nAPAMSs) by a simple, facile, and eco-friendly one-step reduction
strategy for the fabrication of highly sensitive nonenzymatic H2O2 sensing
interfaces. Energy-dispersive X-ray spectroscopy mapping (EDX mapping), energy
dispersive X-ray spectroscopy analysis (EDX), transmission electron microscopy
(TEM), Fourier transform infrared spectrum (FT-IR), and X-ray diffraction
spectrum (XRD) were employed to characterize RGO/nAPAMSs from a microscopic
perspective. The results of cyclic voltammetry and chronoamperometry exhibited
excellent electrochemical behaviors toward H2O2, with a rapid response time
within 5 s, remarkable sensitivity of 1117.0 MUA mM-1 cm-2, wide linear range of
0.005 to 4.0 mM and lower detection limit of 0.008 MUM (S/N = 3), which provide
RGO/nAPAMS not only a promising prospect for the quantitative detection of H2O2
but also a potential application in other fields of sensors. Moreover, further
analysis showed the principles of the superior H2O2 sensing performance of
RGO/nAPAMSs. This discovery provides a significant contribution to future study
in nonenzymatic H2O2 sensing based on Nano Pt, Nano Au noble metal
electrocatalysts.
PMID- 29337578
TI - Physiologically Based Pharmacokinetic Modeling in Lead Optimization. 1.
Evaluation and Adaptation of GastroPlus To Predict Bioavailability of Medchem
Series.
AB - When medicinal chemists need to improve bioavailability (%F) within a chemical
series during lead optimization, they synthesize new series members with
systematically modified properties mainly by following experience and general
rules of thumb. More quantitative models that predict %F of proposed compounds
from chemical structure alone have proven elusive. Global empirical %F
quantitative structure-property (QSPR) models perform poorly, and projects have
too little data to train local %F QSPR models. Mechanistic oral absorption and
physiologically based pharmacokinetic (PBPK) models simulate the dissolution,
absorption, systemic distribution, and clearance of a drug in preclinical species
and humans. Attempts to build global PBPK models based purely on calculated
inputs have not achieved the <2-fold average error needed to guide lead
optimization. In this work, local GastroPlus PBPK models are instead customized
for individual medchem series. The key innovation was building a local QSPR for a
numerically fitted effective intrinsic clearance (CLloc). All inputs are
subsequently computed from structure alone, so the models can be applied in
advance of synthesis. Training CLloc on the first 15-18 rat %F measurements gave
adequate predictions, with clear improvements up to about 30 measurements, and
incremental improvements beyond that.
PMID- 29337579
TI - Unveiling the Shape Evolution and Halide-Ion-Segregation in Blue-Emitting
Formamidinium Lead Halide Perovskite Nanocrystals Using an Automated Microfluidic
Platform.
AB - Hybrid organic-inorganic perovskites and in particular formamidinium lead halide
(FAPbX3, X = Cl, Br, I) perovskite nanocrystals (NCs) have shown great promise
for their implementation in optoelectronic devices. Specifically, the Br and I
counterparts have shown unprecedented photoluminescence properties, including
precise wavelength tuning (530-790 nm), narrow emission linewidths (<100 meV) and
high photoluminescence quantum yields (70-90%). However, the controlled formation
of blue emitting FAPb(Cl1-xBrx)3 NCs lags behind their green and red counterparts
and the mechanism of their formation remains unclear. Herein, we report the
formation of FAPb(Cl1-xBrx)3 NCs with stable emission between 440 and 520 nm in a
fully automated droplet-based microfluidic reactor and subsequent reaction
upscaling in conventional laboratory glassware. The thorough parametric screening
allows for the elucidation of parametric zones (FA-to-Pb and Br-to-Cl molar
ratios, temperature, and excess oleic acid) for the formation of nanoplatelets
and/or NCs. In contrast to CsPb(Cl1-xBrx)3 NCs, based on online parametric
screening and offline structural characterization, we demonstrate that the
controlled synthesis of Cl-rich perovskites (above 60 at% Cl) with stable
emission remains a challenge due to fast segregation of halide ions.
PMID- 29337580
TI - Spatiotemporal Control of Pre-existing Alkene Geometry: A Bio-Inspired Route to 4
Trifluoromethyl-2H-chromenes.
AB - Routes to prepare C4-trifluoromethyl analogues of the 2H-chromene scaffold are
scarce: this is particularly striking given the importance of fluorine in
pharmaceutical development. To address this limitation, a facile strategy has
been developed that is reliant on catalytic, geometric isomerization of easily
accessible allylic alcohols (up to >95:5) followed by intramolecular cyclization
via Pd catalysis (up to 96%). This concise biomimetic approach emulates the
photoisomerization/cyclization cascade inherent to phenylpropanoid biosynthesis.
PMID- 29337581
TI - Light Harvesting by Equally Contributing Mechanisms in a Photosynthetic Antenna
Protein.
AB - We report supramolecular quantum mechanics/molecular mechanics simulations on the
peridinin-chlorophyll a protein (PCP) complex from the causative algal species of
red tides. These calculations reproduce for the first time quantitatively the
distinct peridinin absorptions, identify multichromophoric molecular excitations,
and elucidate the mechanisms regulating the strongly allowed S0 (11Ag-) -> S2
(11Bu+) absorptions of the bound peridinins that span a 58 nm spectral range in
the region of maximal solar irradiance. We discovered that protein binding site
imposed conformations, local electrostatics, and electronic coupling contribute
equally to the spectral inhomogeneity. Electronic coupling causes coherent
excitations among the densely packed pigments. Complementary pairing of tuning
mechanisms is the result of a competition between pigment-pigment and pigment
environment interactions. We found that the aqueous solvent works in concert with
the charge distribution of PCP to produce a strong correlation between peridinin
spectral bathochromism and the local dielectric environment.
PMID- 29337582
TI - Perceiving groups: The people perception of diversity and hierarchy.
AB - The visual perception of individuals has received considerable attention (visual
person perception), but little social psychological work has examined the
processes underlying the visual perception of groups of people (visual people
perception). Ensemble-coding is a visual mechanism that automatically extracts
summary statistics (e.g., average size) of lower-level sets of stimuli (e.g.,
geometric figures), and also extends to the visual perception of groups of faces.
Here, we consider whether ensemble-coding supports people perception, allowing
individuals to form rapid, accurate impressions about groups of people. Across
nine studies, we demonstrate that people visually extract high-level properties
(e.g., diversity, hierarchy) that are unique to social groups, as opposed to
individual persons. Observers rapidly and accurately perceived group diversity
and hierarchy, or variance across race, gender, and dominance (Studies 1-3).
Further, results persist when observers are given very short display times,
backward pattern masks, color- and contrast-controlled stimuli, and absolute
versus relative response options (Studies 4a-7b), suggesting robust effects
supported specifically by ensemble-coding mechanisms. Together, we show that
humans can rapidly and accurately perceive not only individual persons, but also
emergent social information unique to groups of people. These people perception
findings demonstrate the importance of visual processes for enabling people to
perceive social groups and behave effectively in group-based social interactions.
(PsycINFO Database Record
PMID- 29337583
TI - Sudden-death aversion: Avoiding superior options because they feel riskier.
AB - We present evidence of sudden-death aversion (SDA)-the tendency to avoid "fast"
strategies that provide a greater chance of success, but include the possibility
of immediate defeat, in favor of "slow" strategies that reduce the possibility of
losing quickly, but have lower odds of ultimate success. Using a combination of
archival analyses and controlled experiments, we explore the psychology behind
SDA. First, we provide evidence for SDA and its cost to decision makers by
tabulating how often NFL teams send games into overtime by kicking an extra point
rather than going for the 2-point conversion (Study 1) and how often NBA teams
attempt potentially game-tying 2-point shots rather than potentially game-winning
3-pointers (Study 2). To confirm that SDA is not limited to sports, we
demonstrate SDA in a military scenario (Study 3). We then explore two mechanisms
that contribute to SDA: myopic loss aversion and concerns about "tempting fate."
Studies 4 and 5 show that SDA is due, in part, to myopic loss aversion, such that
decision makers narrow the decision frame, paying attention to the prospect of
immediate loss with the "fast" strategy, but not the downstream consequences of
the "slow" strategy. Study 6 finds that people are more pessimistic about a risky
strategy that needn't be pursued (opting for sudden death) than the same strategy
that must be pursued. We end by discussing how these twin mechanisms lead to
differential expectations of blame from the self and others, and how SDA
influences decisions in several different walks of life. (PsycINFO Database
Record
PMID- 29337584
TI - Is antidepressant use associated with difficulty identifying feelings? A brief
report.
AB - Studies on the subjective effects of antidepressants suggest that they may not
only improve depressed mood, but as an adverse effect also cause "emotional
blunting." This phenomenon is poorly understood and little studied. The aim of
this study was to examine the association of serotonergic antidepressant use and
subjective emotional awareness. Emotional awareness was assessed using the
Difficulty Identifying Feelings subscale from the 20-Item Toronto Alexithymia
Scale. Fifty-seven individuals on antidepressant medication and 441 controls were
compared. The effects of sex, age, education, as well as current depressive
symptoms were controlled for. After controlling for selected variables, the
antidepressant group scored higher in subjective difficulty identifying feelings,
compared to controls. (p = .043, Adjusted means by Group 14.2 vs. 15.5, 95%
confidence interval for mean difference between Groups 0.04-2.5). Serotonergic
antidepressant use may be associated with difficulty identifying feelings. Future
studies with a longitudinal setting are warranted to clarify causality. (PsycINFO
Database Record
PMID- 29337585
TI - Narrative theory: II. Self-generated and experimenter-provided negative income
shock narratives increase delay discounting.
AB - Reading experimenter-provided narratives of negative income shock has been
previously demonstrated to increase impulsivity, as measured by discounting of
delayed rewards. We hypothesized that writing these narratives would potentiate
their effects of negative income shock on decision-making more than simply
reading them. In the current study, 193 cigarette-smoking individuals from Amazon
Mechanical Turk were assigned to either read an experimenter-provided narrative
or self-generate a narrative describing either the negative income shock of job
loss or a neutral condition of job transfer. Individuals then completed a task of
delay discounting and measures of affective response to narratives, as well as
rating various narrative qualities such as personal relevance and vividness.
Consistent with past research, narratives of negative income shock increased
delay discounting compared to control narratives. No significant differences
existed in delay discounting after self-generating compared to reading
experimenter-provided narratives. Positive affect was lower and negative affect
was higher in response to narratives of job loss, but affect measures did not
differ based on whether narratives were experimenter-provided or self-generated.
All narratives were rated as equally realistic, but self-generated narratives
(whether negative or neutral) were rated as more vivid and relevant than
experimenter-provided narratives. These results indicate that the content of
negative income shock narratives, regardless of source, consistently drives short
term choices. (PsycINFO Database Record
PMID- 29337587
TI - Use of lactic acid bacteria and yeasts to reduce exposure to chemical food
contaminants and toxicity.
AB - Chemical contaminants that are present in food pose a health problem and their
levels are controlled by national and international food safety organizations.
Despite increasing regulation, foods that exceed legal limits reach the market.
In Europe, the number of notifications of chemical contamination due to pesticide
residues, mycotoxins and metals is particularly high. Moreover, in many parts of
the world, drinking water contains high levels of chemical contaminants owing to
geogenic or anthropogenic causes. Elimination of chemical contaminants from water
and especially from food is quite complex. Drastic treatments are usually
required, which can modify the food matrix or involve changes in the forms of
cultivation and production of the food products. These modifications often make
these treatments unfeasible. In recent years, efforts have been made to develop
strategies based on the use of components of natural origin to reduce the
quantity of contaminants in foods and drinking water, and to reduce the quantity
that reaches the bloodstream after ingestion, and thus, their toxicity. This
review provides a summary of the existing literature on strategies based on the
use of lactic acid bacteria or yeasts belonging to the genus Saccharomyces that
are employed in food industry or for dietary purposes.
PMID- 29337586
TI - Differential development of acute tolerance may explain heightened rates of
impaired driving after consumption of alcohol mixed with energy drinks versus
alcohol alone.
AB - Consumers of alcohol mixed with energy drinks (AmED) are more likely to drive
while impaired when compared to alcohol alone consumers. In addition, acute
tolerance to the internal cues of feelings of intoxication is known to contribute
to maladaptive decisions to drive while impaired. Therefore, the purpose of this
study was to determine whether there is differential development of acute
tolerance for AmED versus alcohol alone for ratings of willingness to drive after
alcohol consumption. Social drinkers (n = 12) attended 4 separate sessions where
they received alcohol and energy drinks, alone and in combination. The
development of acute tolerance to alcohol was assessed for several objective (a
computerized cued go/no-go reaction time task) and subjective measures at matched
breath alcohol concentrations (BrACs) for the ascending and descending limbs of
the BrAC curve. The results indicated that alcohol administration decreased
willingness to drive ratings. Acute tolerance was observed in the AmED dose
condition for only the willingness to drive ratings that were significantly
higher on the descending versus ascending test. Alcohol-induced impairments of
the computer task performance did not exhibit any acute tolerance. Therefore, the
differential development of acute tolerance may explain why many studies observe
higher rates of impaired driving for AmED consumers compared to alcohol alone
consumers. Because drunk driving is a major public health concern, alcohol
consumers should be warned that the use of energy drink mixers with alcohol could
lead to a false sense of security in one's ability to drive after drinking.
(PsycINFO Database Record
PMID- 29337588
TI - An Argument for the Protocolized Screening and Management of Post-Extubation
Stridor.
PMID- 29337589
TI - Critical Review on the Analytical Mechanistic Steps in the Evaluation of
Antioxidant Activity.
AB - Electrophysiological systems are prone to release free radicals for functioning
of biological system with proper balancing of antioxidant-prooxidant ratio for
establishing a healthy living system. The biostress condition releases different
reactive oxygen species, such as hydroxyl, alkoxyl, superoxide, hydrogen
peroxide, hydroperoxyl, ozone, singlet oxygen, hypochlorus acid, thiyl radical,
etc. This review tries to discuss the general aspects of the antioxidant assay
methodologies that are currently used for the detection of antioxidant property.
The entire review has been divided into three different sections. The first deals
with the release of free radical by mitochondrial dysfuctioning and its curbing
action by local antioxidants. The second and third sections discuss the general
procedure adopted and reaction mechanism involved in the assay procedure along
with the limitations and advantages.
PMID- 29337591
TI - Reply to Smith et al.: An Argument for the Protocolized Screening and Management
of Post-Extubation Stridor.
PMID- 29337590
TI - Novel Mechanism for Nicotinamide Phosphoribosyltransferase Inhibition of TNF
alpha-mediated Apoptosis in Human Lung Endothelial Cells.
AB - Nicotinamide phosphoribosyltransferase (NAMPT) exists as both intracellular NAMPT
and extracellular NAMPT (eNAMPT) proteins. eNAMPT is secreted into the blood and
functions as a cytokine/enzyme (cytozyme) that activates NF-kappaB signaling via
ligation of Toll-like receptor 4 (TLR4), further serving as a biomarker for
inflammatory lung disorders such as acute respiratory distress syndrome. In
contrast, intracellular NAMPT is involved in nicotinamide mononucleotide
synthesis and has been implicated in the regulation of cellular apoptosis,
although the exact mechanisms for this regulation are poorly understood. We
examined the role of NAMPT in TNF-alpha-induced human lung endothelial cell (EC)
apoptosis and demonstrated that reduced NAMPT expression (siRNA) increases EC
susceptibility to TNF-alpha-induced apoptosis as reflected by PARP-1 cleavage and
caspase-3 activation. In contrast, overexpression of NAMPT served to reduce
degrees of TNF-alpha-induced EC apoptosis. Inhibition of nicotinamide
mononucleotide synthesis by FK866 (a selective NAMPT enzymatic inhibitor) failed
to alter TNF-alpha-induced human lung EC apoptosis, suggesting that NAMPT
dependent NAD+ generation is unlikely to be involved in regulation of TNF-alpha
induced EC apoptosis. We next confirmed that TNF-alpha-induced EC apoptosis is
attributable to NAMPT secretion into the EC culture media and subsequent eNAMPT
ligation of TLR4 on the EC membrane surface. Silencing of NAMPT expression,
direct neutralization of secreted eNAMPT by an NAMPT-specific polyclonal antibody
(preventing TLR4 ligation), or direct TLR4 antagonism all served to significantly
increase EC susceptibility to TNF-alpha-induced EC apoptosis. Together, these
studies provide novel insights into NAMPT contributions to lung inflammatory
events and to novel mechanisms of EC apoptosis regulation.
PMID- 29337592
TI - Concentrations of Blood Components in Commercial Platelet-Rich Plasma Separation
Systems: A Review of the Literature.
AB - BACKGROUND: Platelet-rich plasma (PRP) has proven to be a very safe therapeutic
option in the treatment of tendon, muscle, bone, and cartilage injuries.
Currently, several commercial separation systems are available for the
preparation of PRP. The concentrations of blood components in PRP among these
separation systems vary substantially. PURPOSE: To systematically review and
evaluate the differences between the concentrations of blood components in PRP
produced by various PRP separation systems. STUDY DESIGN: Systematic review.
METHODS: MEDLINE/PubMed, the Cochrane Central Register of Controlled Trials
(CENTRAL), and EMBASE were searched for studies that compared the concentrations
of blood components and growth factors in PRP between various separation systems
and studies that reported on the concentrations of blood components and growth
factors of single separation systems. The primary outcomes were platelet count,
leukocyte count, and concentration of growth factors (eg, platelet-derived growth
factor-AB [PDGF-AB], transforming growth factor-beta1 [TGF-beta1], and vascular
endothelial growth factor [VEGF]). Furthermore, the preparation protocols and
prices of the systems were compared. RESULTS: There were 1079 studies found, of
which 19 studies were selected for inclusion in this review. The concentrations
of platelets and leukocytes in PRP differed largely between, and to a lesser
extent within, the studied PRP separation systems. Additionally, large
differences both between and within the studied PRP separation systems were found
for all the growth factors. Furthermore, preparation protocols and prices varied
widely between systems. CONCLUSION: There is a large heterogeneity between PRP
separation systems regarding concentrations of platelets, leukocytes, and growth
factors in PRP. The choice for the most appropriate type of PRP should be based
on the specific clinical field of application. As the ideal concentrations of
blood components and growth factors for the specific fields of application are
yet to be determined for most of the fields, future research should focus on
which type of PRP is most suitable for the specific field.
PMID- 29337593
TI - Active December Caps Historic Year For Reform.
AB - The month brought the repeal of the individual mandate's penalties, but also 2018
enrollment numbers rivaling those of 2017.
PMID- 29337594
TI - Solid Phase Microextraction Techniques in Determination of Biomarkers.
AB - The detection and quantification of biomarkers is gaining attention in medical
research and diagnostics communities. Biomarkers cover a range from gases to
biological macromolecules. Because of the nanomolar range levels of typical
biomarkers in plasma, blood, urine, exhalation samples, and other biological
fluids as well as complex matrix of biological media, adequate sample preparation
methods should be used for quantification of biomarkers. The performance of an
analytical method for biomarkers should support reproducible and accurate data.
In the present paper, recent progress in well-established solid phase
microextraction (SPME) methods for the clinical analysis are reviewed and
discussed.
PMID- 29337595
TI - Outcome of extraocular retinoblastoma in a resource limited center from low
middle income country.
AB - Retinoblastoma (RB) is the most common ocular malignancy in children, and is
managed by multimodal treatment. There is a paucity of data regarding the
clinical profile and outcome of children with extraocular retinoblastoma from Low
Middle Income Countries (LMIC) including India. Case records of children with
newly diagnosed extraocular RB from January 2013 to August 2016 treated at our
unit were analysed for clinical profile, treatment, and outcome. Over the 44
month study period, 91 children were diagnosed with RB, out of which 41 had
extraocular disease. While 26 children had extraocular spread limited to orbit
(IRSS stage III), 15 had a distant spread to brain (IRSS stage IV). Median lag
period for diagnosis was eight months. Treatment abandonment rates were 38.5% and
46.6% in International Retinoblastoma Staging System (IRSS) stage III and IV
respectively. With a median follow up of 31.5 months, the projected overall
survival for IRSS III at one, two, and three years was 87.5%, 55.6%, and 39.7%.
All patients with stage IV disease died after a median follow up duration of
three months. High treatment abandonment rates and limited availability of
resources lead to suboptimal survival in children with extraocular RB from LMIC.
Initiatives aimed at improving early diagnosis, so that the disease is detected
in the intraocular stage, are critical to improve the survival in children with
RB.
PMID- 29337596
TI - The Influence of Graft Fixation Methods on Revision Rates After Primary Anterior
Cruciate Ligament Reconstruction.
AB - BACKGROUND: The method of graft fixation in primary anterior cruciate ligament
(ACL) reconstruction is important for initial stability of the graft. Poor graft
fixation can result in failure of the reconstruction. The effect of ACL graft
fixation principles and fixation implant combinations on the risk of revision
after ACL reconstruction is not well understood. PURPOSE: The study aimed to
compare the risk of revision among 4 categories of femoral fixation divided by
their principle of function using a hamstring tendon (HT) graft only.
Furthermore, this study aimed to compare the risk of revision among the most
frequently used combinations (tibia and femur) of graft fixation implants in a
national patient cohort. STUDY DESIGN: Cohort study; Level of evidence, 3.
METHODS: The authors divided the femoral fixation constructs into 4 categories by
their principle of function: cortical suspensory fixation, adjustable cortical
suspensory fixation, intratunnel transfixation, and interference screw (aperture)
fixation. Data on revision rates and graft fixation methods were extracted from
the Danish ACL Reconstruction Registry. The study included patients who underwent
primary ACL reconstruction with either an HT or patellar tendon (PT) graft and
were followed up at 2 to 10 years. Revision rates at 2-year and full follow-up
were extracted for the category of graft fixation in the femur as well as for the
most common implant combinations (those involving >175 patients). Patients with
infrequently used fixation devices were excluded from this analysis. The HT group
included 14 frequently used combinations (n > 175), and there were 2 such
combinations in the PT group. A total of 13,200 ACL reconstructions were included
in the study. For ACL reconstruction with an HT graft, there were 4680 with
cortical suspensory fixation, 577 with adjustable cortical suspensory fixation,
5921 with intratunnel transfixation, and 617 with interference screw fixation.
There were 1405 ACL reconstructions with a PT graft. RESULTS: When only comparing
primary ACL reconstructions using an HT graft, cortical suspensory fixation
exhibited a significantly higher risk of revision at 2-year follow-up than the
other categories of femoral fixation (hazard ratio [HR], 1.24 [95% CI, 1.07
1.44]; P < .05). Intratunnel transfixation exhibited a significantly lower risk
of revision (HR, 0.83 [95% CI, 0.73-0.94]; P < .05). Comparing the most
frequently used femoral/tibial fixation implant combinations with the mean risk
of revision, Endobutton/Intrafix and Endobutton/Biosure PEEK for HT grafts
exhibited an increased risk of revision, with an relative risk (RR) of 1.36 (95%
CI, 1.03-1.81; P < .05) and 1.55 (95% CI, 1.15-2.09; P < .05), respectively. The
Atlantech metal screw/metal screw and Softsilk/Softsilk combinations (both for PT
grafts) exhibited a significantly decreased risk of revision, with an RR of 0.41
(95% CI, 0.18-0.91; P < .05) and 0.36 (95% CI, 0.15-0.87; P < .05), respectively.
CONCLUSION: When comparing ACL graft fixation methods in the 4 categories using
an HT graft, cortical suspensory fixation was found to have a significantly
increased risk of revision, while intratunnel transfixation exhibited a lower
risk of revision. Both Endobutton/Intrafix and Endobutton/Biosure PEEK implant
combinations exhibited a significantly higher risk of revision. For PT grafts,
Atlantech metal screw/metal screw and Softsilk/Softsilk exhibited a significantly
lower risk of revision.
PMID- 29337597
TI - Hydroxyurea for lifelong transfusion-dependent beta-thalassemia: A meta-analysis.
AB - OBJECTIVE: Chronic blood transfusion remains the most feasible therapeutic option
for lifelong transfusion-dependent beta-thalassemia (lifelong TDbetaT). However,
it is associated with serious risks and complications. Hydroxyurea (HU), an oral
chemotherapeutic drug, is expected to increase hemoglobin levels, thereby
minimizing the burden of blood transfusion and its complications. Growing
literature over the last twenty years suggests promising results of the use HU in
lifelong TDbetaT; however, its role and safety remain unanswered questions. The
objective of this study was to evaluate the clinical efficacy and safety of HU in
patients with lifelong TDbetaT. METHODS: MEDLINE, EMBASE, Cochrane databases, and
major preceding conferences for studies that assessed HU in lifelong TDbetaT
patients were searched. The effect size was estimated as a proportion
(responder/sample size). RESULTS: Eleven observational studies, collectively
involving 859 patients, fulfilled eligibility criteria. HU was associated with a
significant decrease in transfusion need with complete and overall (>=50%)
response rates of 26% [95% confidence interval (CI), 13-41%] and 60% (95% CI, 41
78%), respectively. No serious adverse effects were reported. All of the studies
had several limitations, such as lack of a comparison group. CONCLUSION: HU
appears to be effective, well tolerated; however, large randomized clinical
trials should be done to confirm such findings.
PMID- 29337598
TI - Comparative Study of Intramedullary Hammertoe Fixation.
AB - BACKGROUND: Temporary Kirschner wire fixation (K-wire) is a widely used, low-cost
fixation method for the correction of hammertoe deformity. Reported complications
associated with K-wires prompted the development of new implants over the past
decade. However, there is a lack of literature on comparative studies analyzing
functional outcomes using validated questionnaires. The purpose of this study was
to analyze functional outcomes in patients who had undergone proximal
interphalangeal joint fusion using 2 types of intramedullary implant, the Smart
Toe and the TenFuse, and to compare them with the outcomes in patients treated
with standard K-wire fixation. METHODS: A retrospective review of operative
hammertoe correction by a single surgeon was performed in 96 patients followed
for more than 12 months. Functional outcome was assessed using the Foot Function
Index (FFI), the Short Form 36 (SF-36), and the 10-point visual analog scale
(VAS) validated questionnaires. Complications and fusion rates were also
evaluated. Several patients in the study underwent corrections in different toes;
thus, a total of 186 toes were included in the study. From these, 65 toes (34.9%)
were treated with K-wire fixation, 94 (50.5%) with Smart Toe titanium implant,
and 27 (14.5%) with TenFuse allograft implant. RESULTS: No statistically
significant differences in functional outcome and incidence of complications were
observed among the 3 fixation groups, although the 2 intramedullary implants were
associated with greater fusion rates and patient satisfaction. Breakage of the
Smart Toe implant was significantly higher than that of the other fixations, with
10.6% of implants breaking within the first year postoperatively. SF-36 and VAS
scores decreased 12 months after surgery for the 3 types of fixation, with no
statistically significant differences observed. CONCLUSION: The use of Smart Toe
and TenFuse implants provided operative outcomes comparable to those obtained
using a K-wire fixation and slightly better patient satisfaction. Our results
suggest that utilization of these implants for hammertoe correction was a
reasonable choice that provided good alignment, pain reduction, and improved
function at final follow-up. However, they are more expensive than K-wires. For
this reason, in-depth cost-benefit studies would be required to justify their use
as a standard treatment. LEVEL OF EVIDENCE: Level III, comparative series.
PMID- 29337599
TI - Pearson syndrome.
AB - INTRODUCTION: Pearson syndrome (PS) is a sporadic and very rare syndrome
classically associated with single large-scale deletions of mitochondrial DNA and
characterized by refractory sideroblastic anemia during infancy. Areas covered:
This review presents an analysis and interpretation of the published data that
forms the basis for our understanding of PS. PubMed, Google Scholarand Thompson
ISI Web of Knowledge were searched for relevant data. Expert commentary: PS is a
very rare mitochodrial disease that involves different organs and systems.
Clinical phenotype is extremely variable and may change over the course of
disease itself with the possibility both of worsenings and improvements. Outcome
is invariably lethal and at the moment no cure is available. Accurate supportive
treatment and follow up program in centres with experience in mitochondrial
diseases and marrow failure may positively influence quality and duration of
life.
PMID- 29337600
TI - Developing a theoretical foundation to change road user behavior and improve
traffic safety: Driving under the influence of cannabis (DUIC).
AB - OBJECTIVES: This study explored a theoretical model to assess the influence of
culture on willingness and intention to drive under the influence of cannabis
(DUIC). This model is expected to guide the design of strategies to change future
DUIC behavior in road users. METHODS: This study used a survey methodology to
obtain a nationally representative sample (n = 941) from the AmeriSpeak Panel.
Survey items were designed to measure aspects of a proposed definition of traffic
safety culture and a predictive model of its relationship to DUIC. RESULTS:
Although the percentage of reported past DUIC behaviors was relatively low
(8.5%), this behavior is still a significant public health issue-especially for
younger drivers (18-29 years), who reported more DUIC than expected. Findings
suggest that specific cultural components (attitudes, norms) reliably predict
past DUIC behavior, general DUIC willingness, and future DUIC intention. Most
DUIC behavior appears to be deliberate, related significantly to willingness and
intention. Intention and willingness both appear to fully moderate the
relationship between traffic safety culture and DUIC behavior. CONCLUSIONS: This
study explored a theoretical model to understand road user behavior involving
drug (cannabis)-impaired driving as a significant risk factor for traffic safety.
By understanding the cultural factors that increase DUIC behavior, we can create
strategies to transform this culture and sustain safer road user behavior.
PMID- 29337601
TI - Mango kernel fat fractions as potential healthy food ingredients: A review.
AB - Mango kernel fat (MKF) has been reported to have high functional and nutritional
potential. However, its application in food industry has not been fully explored
or developed. In this review, the chemical compositions, physical properties and
potential health benefits of MKF are described. MKF is a unique fat consisting of
28.9-65.0% of 1,3-distearoyl-2-oleoyl-glycerol with excellent oxidative stability
index (58.8-85.2 h at 110 degrees C), making the fat and its fractions suitable
for use as high-value added food ingredients such as cocoa butter alternatives,
trans-free shortenings, and a source of natural antioxidants (e.g., sterol,
tocopherol and squalene). Unfortunately, the long period of dehydration of mango
kernels at hot temperature results in the hydrolysis of triacylglycerols. The
high levels of hydrolysates (mainly free fatty acids and diacylglycerols) limit
the application of MKF in manufacturing these food ingredients. It is suggested
that the physico-chemical and functional properties of MKF could be further
improved through moderated refining (e.g., degumming and physical
deacidification), fractionation, and interesterification.
PMID- 29337602
TI - Defining the Learning Curve for Hip Arthroscopy: A Threshold Analysis of the
Volume-Outcomes Relationship.
AB - BACKGROUND: Hip arthroscopy has emerged as a successful option for the treatment
of femoroacetabular impingement and related hip disorders, but the procedure is
technically challenging. PURPOSE: To define the learning curve through which
surgeons become proficient at hip arthroscopy. STUDY DESIGN: Cohort study; level
of evidence, 3. METHODS: The authors identified hip arthroscopy procedures
performed by surgeons through a New York State database (Statewide Planning and
Research Cooperative System) and followed those cases for additional hip surgery
(total hip arthroplasty, hip resurfacing, or ipsilateral hip arthroscopy) within
5 years of the original procedure. Career volume for each case was calculated as
the number of hip arthroscopy procedures that the surgeon had performed. Volume
strata were identified via the stratum-specific likelihood ratio method. A Cox
proportional hazards model was used to measure the effect of surgeon career
volume on risk of additional hip surgery, adjusting for the following patient
characteristics: age, sex, race/ethnicity, insurance type, and concurrent
diagnosis of hip osteoarthritis. RESULTS: Among 8041 hip arthroscopies performed
by 251 surgeons, 989 (12.3%) cases underwent additional hip surgery within 5
years. Four strata of surgeon career volume associated with distinct frequencies
of reoperation were identified: cases in the lowest stratum (0-97) had the
highest frequency of additional surgery (15.4%). Frequencies declined for cases
in the medium (98-388), high (389-518), and highest (>=519) strata (13.8%, 10.1%,
and 2.6%, respectively). There was an increased risk of subsequent surgery in
each stratum when compared with the highest stratum (hazard ratio [95% CI]: low
volume, 3.22 [2.29-4.54]; medium, 3.40 [2.41-4.82]; high, 2.81 [1.86-4.25]; P <
.0001 for all). Patients with a diagnosis of hip osteoarthritis had increased
risk of subsequent hip arthroplasty or resurfacing (2.46 [2.09-2.89], P < .0001)
. Risk also increased with age: 30 to 39 vs <=29 years (5.12 [3.29-8.00], P <
.0001), 40 to 49 vs <=29 years (11.30 [7.43-17.190], P < .0001), >=50 vs <=29
years (18.39 [12.10-27.96], P < .0001). Increased age and osteoarthritis were not
risk factors for revision hip arthroscopy. CONCLUSION: The learning curve for hip
arthroscopy was unexpectedly demanding. Cases performed by surgeons with career
volumes >=519 had significantly lower risk of subsequent hip surgery than those
performed by lower-volume surgeons.
PMID- 29337603
TI - An Integrative Review of Nonpharmacological Interventions to Improve Sleep among
Adults with Advanced Serious Illness.
AB - BACKGROUND: Sleep fragmentation is common among those with advanced serious
illness. Nonpharmacological interventions to improve sleep have few, if any,
adverse effects and are often underutilized in these settings. OBJECTIVE: We
aimed to summarize the literature related to nonpharmacological interventions to
improve sleep among adults with advanced serious illness. METHODS: We
systematically searched six electronic databases for literature reporting sleep
outcomes associated with nonpharmacological interventions that included
participants with advanced serious illness during the period of 1996-2016.
RESULTS: From a total of 2731 results, 42 studies met the inclusion criteria. A
total of 31 individual interventions were identified, each evaluated individually
and some in combination with other interventions. Twelve of these studies
employed either multiple interventions within an intervention category (n = 8) or
a multicomponent intervention consisting of interventions from two or more
categories (n = 5). The following intervention categories emerged: sleep hygiene
(1), environmental (6), physical activity (4), complementary health practices
(11), and mind-body practices (13). Of the 42 studies, 22 demonstrated a
statistically significant, positive impact on sleep and represented each of the
categories. The quality of the studies varied considerably, with 17 studies
classified as strong, 17 as moderate, and 8 as weak. CONCLUSIONS: Several
interventions have been demonstrated to improve sleep in these patients. However,
the small number of studies and wide variation of individual interventions within
each category limit the generalizability of findings. Further studies are needed
to assess interventions and determine effectiveness and acceptability.
PMID- 29337604
TI - The Current Status of Outcomes-Based Contracting for Manufacturers and Payers: An
AMCP Membership Survey.
AB - BACKGROUND: As the United States health care system shifts from traditional
volume-based payments to value-based payments, outcomes-based contracts (OBCs)
are gaining popularity among payers and manufacturers as a mechanism for the
shift toward value. Under this model, stakeholders hope to align drug payment and
value to real-world performance metrics (e.g., biomarkers and health care
resource utilization). OBJECTIVE: To understand the experiences, perceptions, and
needs of payers and manufacturers related to OBCs. METHODS: The Academy of
Managed Care Pharmacy (AMCP) and Xcenda conducted an online survey with AMCP
payer and manufacturer members. Participants were asked a series of questions
regarding their use of OBCs, barriers to implementation, and elements required in
establishing successful OBCs. The importance and urgency of specific impediments
to successful OBC implementation were also assessed. RESULTS: The survey was
fielded May 12, 2017, to June 7, 2017, yielding 65 responses (35 payers/30
manufacturers). While a minority of payers/manufacturers had at least 1 OBC in
place (20%/33%), a majority had interest in future OBC use (71%/63%). Among those
with at least 1 OBC in place, 86%/80% of payers/manufacturers had renewed at
least 1 OBC in the past 5 years. All payers and 60% of manufacturers with OBCs
included compliance measures. Improvement in clinical outcomes was also common
(71%/70%) (e.g., reaching set laboratory values goals), and 71%/60% included
avoidance of unnecessary medical resource use (e.g., hospitalization and
emergency department visit). The barrier most frequently identified by payers in
implementing OBCs was evidence that OBCs reduced pharmacy spending (60%), while
manufacturers identified the inability to obtain accurate data/outcome measures
(73%) as a major limiting factor. Payers/manufacturers endorsed the use of easily
measurable outcomes (91%/100%) as most important in establishing successful OBCs.
Manufacturers, and to a lesser extent payers, indicated that regulations and
legal issues need to be addressed to make progress in OBC implementation (e.g.,
safe harbor for preapproval health care economic information [77%/46%] and
exemption of OBCs for best-price requirements [83%/51%]). The only exception was
the clarification of regulations for discussing information outside of an FDA
approved label, in which both manufacturers and payers indicated a very strong
need (100%) to be addressed. CONCLUSIONS: Surveyed AMCP members are interested in
OBCs and recognize their alignment to societal health goals and health care
affordability, although actual use of these contracts has been somewhat limited
to date. Results from this survey indicate that there is potential for OBC use to
increase as barriers and limitations are addressed. DISCLOSURES: This research
was sponsored by the Academy of Managed Care Pharmacy and Xcenda. Duhig, Kaufman,
and Hughes are employed by Xcenda. Saha is employed by the Academy of Managed
Care Pharmacy. Smith has nothing disclose. Study concept and design were
contributed by Duhig, Kaufman, Saha, and Hughes. Kaufman and Hughes collected the
data, and data interpretation was performed by all the authors. The manuscript
was written by Saha, Smith, and Duhig, along with Kaufman and Hughes.
PMID- 29337606
TI - Foodborne Pathogens and Disease Celebrates Its Fifteen Year Anniversary.
PMID- 29337605
TI - Education and Health across Lives and Cohorts: A Study of Cumulative
(Dis)advantage and Its Rising Importance in Germany.
AB - Research from the United States has supported two hypotheses. First, educational
gaps in health widen with age-the cumulative (dis)advantage hypothesis. Second,
this relationship has intensified across cohorts-the rising importance
hypothesis. In this article, we used 23 waves of panel data (Socio-Economic Panel
Study, 1992-2014) to examine both hypotheses in the German context. We considered
individual and contextual influences on the association between education and
health, and we assessed gender differences in health trajectories over the life
course (ages 23 to 84) and across cohorts (born between 1930 and 1969). For
women, we found no support for either hypothesis, as educational gaps in self
rated health remained stable with age and across cohorts. Among men, we found
support for both hypotheses, as educational gaps in self-rated health widened
with age and increasingly in newer cohorts.
PMID- 29337608
TI - Author's Perspectives on Their Highly Cited Papers Published in Foodborne
Pathogens and Disease.
PMID- 29337607
TI - Foodborne Disease Outbreaks in the United States: A Historical Overview.
AB - Understanding the epidemiology of foodborne disease outbreaks (FBDOs) is
important for informing investigation, control, and prevention methods. We
examined annual summary FBDO data in the United States from 1938 to 2015, to help
understand the epidemiology of outbreaks over time. Due to changes in reporting
procedures, before 1998, the mean number of annual outbreaks was 378, and after
that, it was 1062. A mean of 42% had a known etiology during 1961-1998; since
then the etiology has been identified in ~65%, with a marked increase in the
number of norovirus outbreaks. From 1967 to 1997, a mean of 41% of FBDOs occurred
in restaurant settings, increasing to 60% in 1998-2015. Concurrently, the
proportion of outbreaks occurring at a home decreased from 25% to 8%. The mean
size of outbreaks has decreased over time, and the number of multistate outbreaks
has increased. Many social, economic, environmental, technological, and
regulatory changes have dramatically affected the epidemiology of foodborne
disease over time.
PMID- 29337609
TI - Persistent Goose Hemorrhagic Polyomavirus Infection on a Belgian Goose Farm.
AB - Goose hemorrhagic polyomavirus (GHPV) is the causative agent of hemorrhagic
nephritis enteritis of geese (HNEG), one of the major diseases of domestic geese
in Europe. This case report describes a persistent outbreak of a GHPV infection
on a Belgian goose farm. Clinical symptoms, necropsy lesions, and histopathologic
lesions observed were compatible with previous reports of HNEG outbreaks. PCR
analysis confirmed the diagnosis of GHPV. To our knowledge, this is the first
report of an outbreak of a GHPV infection on a Belgian goose farm. This is
evidence that GHPV is not only present in countries known for extensive waterfowl
production, but disease outbreaks also occur in countries with less extensive
goose production.
PMID- 29337611
TI - Interactions Between Parasites and the Bacterial Microbiota of Chickens.
AB - Except for the important role coccidia have as predisposing factors of necrotic
enteritis, the role parasites play in the dynamics of a healthy microbiota of
chickens is not well explored. This review describes the interactions of relevant
intestinal parasites of chickens with bacteria. Infection with Eimeria spp. favor
the growth of Clostridium perfringens and suppress the growth of many other
bacteria by increasing viscosity and passage time of the ingesta, and by causing
lesions to the intestinal mucosa that improve the availability of nutrients for
C. perfringens. Conversely, there are indications that bacteria influence the
course of disease after infections with Eimeria spp. Not much is known about
intestinal cryptosporidiosis in chickens, but results in mice show that the
intestinal microbiota induces some resistance against infection with
Cryptosporidium parvum and that the innate immune response triggered by
infections with cryptosporidia might have an effect on other intestinal microbes.
Histomonas meleagridis depend on bacteria in vitro, and in vivo it will cause
lesions in chickens only in the presence of bacteria. Blastocystis spp. are very
common in chickens, but there is no information about interactions with bacteria.
In humans, there is evidence of the correlation of the detection of Blastocystis
and changes in the intestinal microbiota. There are indications of interactions
between Ascaridia galli and various bacteria in chickens and Ascaridia spp. of
mammals are known to produce various types of antimicrobial molecules. However,
often the underlying mechanisms of these interactions between parasites and
bacteria remain unknown and only correlations but not causation can be
established.
PMID- 29337612
TI - Impact of Controlling Bacteria in Feed on Broiler Performance During a
Clostridial Challenge.
AB - Three studies were conducted using Clostridium perfringens as an intestinal
challenge to produce necrotic enteritis (NE). The studies consisted of two
battery screening studies and one production study in floor pens. The purpose of
the trials was to determine if reducing the level of microorganisms in feed
consumed by broilers reduced the impact of a nonfeed-based Clostridial challenge.
In all studies, C. perfringens challenged broilers consuming feed containing
lower levels of microorganisms compared to control feed exhibited significantly (
P < 0.05) better feed conversion (feed conversion was improved by 14% in battery
trials and by 4.2% in the pen trial) than did C. perfringens-challenged broilers
consuming control feed. In battery trials, body weight gain and NE-associated
mortality were also significantly improved in C. perfringens-challenged broilers
consuming feed containing lower levels of microorganisms (16.5% improvement in
body weight gain and 72.5% reduction in NE-associated mortality). In the pen
trial, body weight gain and NE-associated mortality appeared unaffected by feed
microbial quality. No effect was observed on lesion scores. The present data
indicate that reducing the level of microorganisms in feed can ameliorate some of
the performance losses associated with a Clostridia challenge.
PMID- 29337613
TI - Molecular Detection of Avian Influenza Virus from Sediment Samples in Waterfowl
Habitats on the Delmarva Peninsula, United States.
AB - Avian influenza viruses (AIV) affect many species of birds including waterfowl
and may persist in sediment in aquatic habitats. Sediment samples were collected
from two areas representative of prime migration and overwintering waterfowl
habitat in Dorchester County, Maryland in the fall and winter of 2013-2014.
Samples were screened for the presence of AIV via reverse transcriptase
quantitative PCR targeting the matrix gene. Although 13.6% of sediment samples
were positive for the AIV matrix gene across all collection dates and locations,
differences in detection were noted with location and collection season.
Percentage of AIV-positive sediment samples recovered corresponded to trends in
waterfowl abundance at collection sites both temporally and spatially. These
findings provide further support for the assertion that the presence of AIV in
the aquatic environment is likely affected by the total number, site-specific
density, and array of waterfowl species.
PMID- 29337614
TI - Response of House Finches Recovered from Mycoplasma gallisepticum to Reinfection
with a Heterologous Strain.
AB - After recovery, house finches ( Haemorhous mexicanus) reinfected with the same
Mycoplasma gallisepticum strain remain partially resistant to reinfection for at
least 14 mo in that they recover from reinfection much more rapidly than do
Mycoplasma gallisepticum-naive birds. To test the response of birds to
reinfection with a heterologous strain we performed two experiments. In a first
experiment we exposed birds to one of three strains that differed in virulence.
After they had recovered all were reinfected with the most virulent-strain
available at the time of the experiment. In a second experiment we infected and
later reinfected house finches with one of two Mycoplasma gallisepticum strains
whereby we switched the order of the strain used. In both experiments, disease in
birds reinfected with a more-virulent strain caused more-severe disease. Our data
suggest that the observed increase in Mycoplasma gallisepticum virulence, once
the disease has become endemic in free-ranging house finches is-in part-driven by
increased resistance of recovered birds to strains of equal or lower virulence.
PMID- 29337615
TI - Efficacy of Massachusetts and 793B Vaccines Against Infectious Bronchitis
Moroccan-Italy 02 Virus in Specific-Pathogen-Free Chickens and Commercial
Broilers.
AB - The ability of commercial vaccines H120 and 4/91 to protect against Moroccan
Italy 02 infectious bronchitis virus (Mor-It02) was investigated in specific
pathogen-free (SPF) chickens and commercial broiler chickens. Commercial broiler
chicks (Experiment 1) were vaccinated at the hatchery with H120 vaccine at Day 1,
and challenged at Day 21 with 104 50% egg-infective dose (EID50) of Mor-It02. All
chicks were observed daily for clinical signs attributable to Mor-It02 infection
during the 10 days postchallenge (pc). At 5 and 10 days pc, chicks were humanely
sacrificed for necropsy examination, and tissues were collected for
histopathology evaluation. To better understand the findings on commercial
broilers, day-old SPF chicks were divided into five groups in a second
experiment: Group Mass/4-91, vaccinated with H120 and 4/91 respectively at Days 1
and 15 of age; Group Mass/Mass, vaccinated by H120 at Days 1 and 15; Group Mass,
vaccinated with H120 at Day 1; Group NV, kept unvaccinated; and Group NC, kept as
a negative control (unchallenged). At Day 24 of age, Groups Mass/4-91, Mass/Mass,
Mass, and NV were challenged with 104 EID50 of Mor-It02. In both experiments,
blood samples were collected at different periods for serologic analyses.
Oropharyngeal swabs were collected for virus detection by reverse-transcription
PCR. In Experiments 1 and 2, respiratory signs started as early as 24 hr pc and
maximum severity was observed on Days 3 and 4 pc. The viral shedding rate was
significantly lower in Group Mass/4-91 compared to other challenged groups.
Serologic analysis in both experiments showed that the sera of challenged group
exhibited significantly higher antibody titers than sera collected before
challenge. Histopathologic investigations in SPF birds showed deciliation and
hyperplasia in Group NV and less-pronounced lesions in Groups Mass/Mass and Mass.
In commercial broilers vaccinated with H120 alone, hyperplasia and deciliation
were observed in 90% of the tracheas. These experiments illustrated that Mor-It02
is pathogenic for chickens and a combination of live H120 and 4/91 vaccines given
respectively at Day 1 and Day 15 of age confer a good protection against Mor
It02.
PMID- 29337616
TI - Chronologic Analysis of Gross and Histologic Lesions Induced by Field Strains of
FAdV-1, FAdV-8b, and FAdV-11 in Six-Week-Old Chickens.
AB - Inclusion body hepatitis (IBH) is a disease affecting broiler chicken flocks
worldwide. Several serotypes of fowl adenovirus (FAdV) have been implicated in
disease outbreaks, with and without immunosuppression as a predisposing factor.
IBH usually occurs in flocks up to 30 days of age; it is seldom seen in older
birds. The objective of this study was to determine whether the pathogenicity for
older birds of three FAdV field strains, belonging to serotypes 1, 8b, and 11, in
the absence of immunosuppressive factors, was akin to that for younger birds, and
to establish an effective and economical disease model for assessing cross
protection between serotypes. To achieve this objective, the gross pathology,
histopathology, and dissemination of virus were examined at multiple time points
after inoculation of 6-wk-old, specific-pathogen-free chickens via
intraperitoneal injection. Both FAdV-8b and FAdV-11 generated lesions typical of
those associated with outbreaks of IBH, and they were shown to be primary
pathogens. The presence and severity of hepatic lesions were used to define two
disease stages: degeneration (1-5 days postinoculation) and convalescence (6-14
days postinoculation). During the degenerative stage, FAdV-8b was detected in the
liver, kidney, and gizzard of most birds, whereas FAdV-11 was predominantly
detected in the liver, and both viruses persisted in the gizzard into
convalescence. The pathogenesis of two IBH-associated FAdV strains in 6-wk-old
chickens confirms their high level of virulence and also provides an effective
experimental model for investigation of cross-protection between FAdVs. It also
demonstrates persistence of the virus in the gizzard long after infection,
supporting the notion that it is a site of viral shedding.
PMID- 29337617
TI - Intrapulmonary Delivery of CpG-ODN Microdroplets Provides Protection Against
Escherichia coli Septicemia in Neonatal Broiler Chickens.
AB - Synthetic oligodeoxynucleotides (ODN) containing unmethylated cytosine
phosphodiester guanine (CpG) motifs (CpG-ODN) are effective immunostimulatory
agents against a variety of viral, bacterial, and protozoan diseases in different
animals including poultry. We have recently demonstrated that in ovo injection of
CpG-ODN confers protection in neonatal chickens against bacterial septicemias.
The objective of this study was to investigate the effectiveness of needle-free
intrapulmonary (IPL) delivery of CpG-ODN microdroplets against Escherichia coli
infection in neonatal chicks. In the present study, we used 880 chicks in total
keeping 40 chicks per group. Chicks were delivered CpG-ODN or saline by IPL at
the day 1 of hatch. Three days later, chicks were challenged with two doses (1 *
104 CFU, n = 20 or 1 * 105 CFU, n = 20) of E. coli. Chicks treated with CpG-ODN
by the IPL route had significantly lower clinical signs and bacterial load
compared to the group treated with saline ( P < 0.05). CpG-ODN-treated groups
were significantly protected against E. coli septicemia. We observed dose- and
exposure time-dependent immunoprotective effects of IPL CpG-ODN in chicks. We
found that IPL delivery of CpG-ODN can induce protective immunity as early as 6
hr that remains effective at least until day 5 post-treatment. Moreover, there
were no adverse effects of IPL delivery of CpG-ODN on growth or mortality up to
42 days of age. Based on these findings, it can be suggested that CpG-ODN
delivery by IPL route can be a promising alternative to antibiotics for inducing
protective immunity in chicks during the critical first week of neonatal life.
PMID- 29337618
TI - Vegetative Valvular Endocarditis and Hepatitis Associated with Helcococcus ovis
in a 7-year-old White Leghorn Rooster.
AB - Helcococcus ovis is a slow-growing, pyridoxal-dependent, Gram-positive coccus
belonging to the Peptostreptococcaceae family. Bacteria belonging to the genus
Helcococcus are considered normal inhabitants of keratinized epithelium in
humans; however, several reports support their role as pathogens in humans and
several animal species. This case report describes the identification of H. ovis
in a white leghorn rooster with valvular vegetative endocarditis and hepatitis.
In February 2017 one dead, 7-yr-old, white leghorn rooster was submitted to the
California Animal Health and Food Safety Turlock laboratory for diagnostic
testing. Postmortem and microscopic examination revealed vegetative endocarditis
and aortic thrombosis associated with large numbers of Gram-positive cocci.
Myocarditis and extensive necrotic hepatitis were also noticed. Helcococcus ovis
was isolated in large numbers from the aortic endothelium and confirmed by matrix
assisted laser desorption ionization time-of-flight mass spectrometry. Bacterial
colonies become evident 48 hr postincubation and exhibited a satellite growth
around Escherichia coli on blood agar plates. A similar relationship has been
described between Helcococcus spp. and Staphylococcus aureus. The primary site of
infection in this chicken was not determined. To our understanding this is the
first report of H. ovis infection in an avian species. The fastidious nature and
nutritional requirements of Helcococcus spp. must be considered in order to allow
proper identification and avoid misdiagnosis. Further studies are needed to
define pathogenesis, virulence factors, and predisposing conditions associated
with this microorganism.
PMID- 29337620
TI - 2017 AAAP Awards.
PMID- 29337619
TI - The Role of Necroptosis, Apoptosis, and Inflammation in Fowl Cholera-Associated
Liver Injury in a Chicken Model.
AB - Fowl cholera resulting from infection with Pasteurella multocida causes huge
economic losses in the poultry industry. Necrotic hepatitis is reported to be a
significant lesion associated with fowl cholera in chickens. Clarifying the
underlying molecular mechanism of hepatic injury caused by P. multocida infection
is needed to develop new strategies to control fowl cholera. Pasteurella
multocida Q (the standard reference strain) and P. multocida 1G1 (a clinical
strain) were used to infect healthy laying hens. Clinical signs were observed and
gross lesions in livers were observed postmortem. Histologic lesions and the
localization and expression of protein molecules associated with necroptosis,
apoptosis, and inflammation in hepatic tissues were examined by hematoxylin and
eosin staining and immunohistochemistry. Western blot analysis was used to
determine the expression of liver injury-related genes. Necroptotic molecules
such as RIPK1 (receptor interaction protein kinases 1), RIPK3 (receptor
interaction protein kinases 3), and MLKL (mixed lineage kinase domain-like
protein) were observed by immunostaining primarily in the cytoplasm of
hepatocytes within or around necrotic foci, and inflammatory mediators HMGB1
(high-mobility group box 1) and IL-6 (interleukin-6) were found in the cytoplasm
of heterophils, monocytes/macrophages, and hepatic sinusoids. In addition, MMP9
(matrix metalloproteinase 9) and TIMP1 (tissue inhibitor of metalloproteinase 1)
were observed in hepatic parenchymal cells, inflammatory cells, and interstitial
spaces, whereas the apoptotic effector molecule caspase-3 (cysteine-containing
aspartic proteolytic enzymes 3) was mainly found in hepatocytes. The expression
of RIPK1, RIPK3, and MLKL was significantly higher in the infected chickens than
in the controls. HMGB1 and IL-6 protein levels were also increased in infected
chickens relative to those in controls. Both MMP9 and TIMP1 were highly expressed
in infected chickens. In addition, caspase-3 protein levels were significantly
elevated in infected chickens. Necroptosis, apoptosis, and inflammation played a
significant role in hepatic injury caused by P. multocida.
PMID- 29337622
TI - Isolation of Avipoxvirus from Tongue of Canaries ( Serinus canaria) Show Severe
Localized Proliferative Glossitis.
AB - Poxvirus was the causative agent of two unusual outbreaks of proliferative
glossitis in canary ( Serinus canaria forma domestica) breeders in the Northern
Italy. A total of 45, 7-9-mo-old canaries were submitted in fair postmortem
conditions to the Istituto Zooprofilattico Sperimentale delle Venezie at the
beginning of November 2005 for diagnostic investigation. Birds belonged to two
unrelated and geographically distant aviaries in northern Italy, herein
identified as Aviary A and Aviary B. The two breeder flocks had both attended the
same bird exposition held at the beginning of October and started experiencing an
onset of high mortality 3 wk after the show. Twelve red factor-melanin canaries
from Aviary A (Mantua) and 33 dominant white and recessive white canaries from
Aviary B (Vicenza) were submitted for laboratory investigations. Clinical signs
were unspecific and consisted of depression, ruffling of the feathers, epistaxis,
and anorexia due to decreased feed and water intake. Postmortem findings revealed
a severe increase in volume, thickening, and hardening of the tongue, which had
turned pinkish to dark brown. No apparent gross lesions were noticed in
integumentary, respiratory, and digestive systems or other internal organs.
Histopathologic evaluation of the tongue revealed severe proliferation of the
stratified squamous epithelium containing numerous large eosinophilic
intracytoplasmic inclusion bodies (Bollinger bodies) displacing the nuclei of the
cells peripherally. Severe ulceration of the surface epithelium,
fibrinoheterophilic plaque formation, and moderate basal lymphoplasmacytic
infiltrations were also associated with the proliferative lesion. Poxvirus was
successfully isolated from the lesions in tissue cultures but not in specific
pathogen-free chicken embryonated eggs. Typical large, brick-shaped viral
particles of 300-450 nm were also observed in affected tongues by transmission
electron microscopy. This is the first report of multiple outbreaks of "poxvirus
glossitis" in canaries.
PMID- 29337623
TI - Fibrillar Collagen Organization Associated with Broiler Wooden Breast Fibrotic
Myopathy.
AB - Wooden breast (WB) is a fibrotic myopathy affecting the pectoralis major (p.
major) muscle in fast-growing commercial broiler lines. Birds with WB are
phenotypically detected by the palpation of a hard p. major muscle. A primary
feature of WB is the fibrosis of muscle with the replacement of muscle fibers
with extracellular matrix proteins, such as collagen. The ability of a tissue to
be pliable and stretch is associated with the organization of collagen fibrils in
the connective tissue areas surrounding muscle fiber bundles (perimysium) and
around individual muscle fibers (endomysium). The objective of this study was to
compare the structure and organization of fibrillar collagen by using
transmission electron microscopy in two fast-growing broiler lines (Lines A and
B) with incidence of WB to a slower growing broiler Line C with no phenotypically
detectable WB. In Line A, the collagen fibrils were tightly packed in a parallel
organization, whereas in Line B, the collagen fibrils were randomly aligned.
Tightly packed collagen fibrils arranged in parallel are associated with
nonpliable collagen that is highly cross-linked. This will lead to a
phenotypically hard p. major muscle. In Line C, the fibrillar collagen was sparse
in its distribution. Furthermore, the average collagen fibril diameter and
banding D-period length were altered in Line A p. major muscles affected with WB.
Taken together, these data are suggestive of different fibrotic myopathies beyond
just what is classified as WB in fast-growing broiler lines.
PMID- 29337625
TI - Molecular Characterization of QX-Like and Variant Infectious Bronchitis Virus
Strains in Malaysia Based on Partial Genomic Sequences Comprising the S-3a/3b-E-M
Intergenic Region-5a/5b-N Gene Order.
AB - Infectious bronchitis virus (IBV) is one of the major poultry pathogens of global
importance. However, the prevalence of IBV strains in Malaysia is poorly
characterized. The partial genomic sequences (6.8 kb) comprising the S-3a/3b-E-M
intergenic region-5a/5b-N gene order of 11 Malaysian IBVs isolated in 2014 and
2015 were sequenced using next-generation sequencing technology. Phylogenetic and
pairwise sequence comparison analysis showed that the isolated IBVs are divided
into two groups. Group 1 (IBS124/2015, IBS125/2015, IBS126/2015, IBS130/2015,
IBS131/2015, IBS138/2015, and IBS142/2015) shared 90%-95% nucleotide and deduced
amino acid similarities to the QX-like strain. Among these isolates, IBS142/2015
is the first IBV detected in Sarawak state located in East Malaysia (Borneo
Island). Meanwhile, IBV isolates in Group 2 (IBS037A/2015, IBS037B/2015,
IBS051/2015, and IBS180/2015) were 91.62% and 89.09% identical to Malaysian
variant strain MH5365/95 (EU086600) at nucleotide and amino acid levels,
respectively. In addition, all studied IBVs were distinctly separate from
Massachusetts (70%-72% amino acid similarity) and European strains including
793/B, Italy-02, and D274 (68%-73% amino acid similarity). Viruses in Group 1
have the insertion of three amino acids at positions 23, 121, and 122 of the S1
protein and recombinant events detected at nucleotide position 4354-5864, with
major parental sequence derived from QX-like (CK-CH-IBYZ-2011) and a minor
parental sequence derived from Massachusetts vaccine strain (H120). This study
demonstrated coexistence of the IBV Malaysian variant strain along with the QX
like strain in Malaysia.
PMID- 29337626
TI - Comparative Analysis of Pasteurella multocida Isolates from Acute and Chronic
Fowl Cholera Cases in Hungary During the Period 2005 Through 2010.
AB - Fowl cholera (FC) is a highly contagious and economically important disease of
poultry worldwide. This study was performed on 218 Pasteurella multocida isolates
collected from separated breeding farms or backyards with acute and chronic FC
cases in multiple localities across Hungary during the period 2005-2010. All
isolates were characterized by a broad range of biochemical, serological, and
molecular methods, as well as their antibiotic susceptibility to aminoglycosides
(A), macrolides (M), penicillins (P), quinolones (Q), cephalosporins,
sulphonamides (S), and tetracyclines (T) was determined. Fifty-two percent of all
isolates belonged to a well-defined type that was highly virulent, caused acute
FC, and had the same character: fermented L-arabinose, possessed capsule type A,
identified as Heddleston serotype 1, and possessed allele type A of the ptfA
fimbrial gene. This type was widely distributed among poultry in Hungary,
especially in waterfowl flocks. Isolates collected from the chronic FC cases were
more diverse: none of them fermented L-arabinose; they possessed capsule type A
(76%), F (9%), or was non-typeable (15%) with different Heddleston serotypes,
mainly 1, 3, 4, and 5, or 7 and 16; in addition, possessed allele type B of ptfA
fimbrial gene. Only 26 isolates presented characters similar to any of the
chronic FC cases but caused severe disease. The antibiotic susceptibility assay
presented that 80% of all isolates were resistant to 1-5 of the studied
antimicrobial agents. During the survey, after two years, there was a dramatic
decline both in the number of the multi-drug resistance phenotypes and the
prevalence of the highly virulent type of the isolates. In the next four years,
multiresistant isolates were almost completely removed, whereas the number of
isolates resistant to 1 or 2 drugs was constant. Reduced frequency of antibiotic
multiresistant, mostly L-arabinose-fermenting isolates, has been observed since
2007. This reduction may be a consequence of the elimination of multiple
waterfowl flocks in Hungary during avian influenza outbreaks, which possibly
created a break in the "transmission chain" of pathogenic P. multocida isolates.
PMID- 29337627
TI - Increased Incidence of Enterococcal Infection in Nonviable Broiler Chicken
Embryos in Western Canadian Hatcheries as Detected by Matrix-Assisted Laser
Desorption/Ionization-Time-of-Flight Mass Spectrometry.
AB - The emergence of enterococcal infections in neonatal broiler chickens in the
poultry industry has become common in many countries, including Canada. The
objective of this study was to examine the bacterial infections in nonviable
broiler chicken embryos in three western Canadian poultry hatcheries using matrix
assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF
MS). The pattern of embryo mortality that occurred during incubation and the
breakout analysis results were similar in all three hatcheries. The majority of
embryo mortality occurred during the late stage of incubation (35.08%), followed
by the early stage of incubation (15.35%). The breakout analysis showed that
65.82% of swabs had at least one type of bacterial growth while 34.17% of swabs
were negative for bacterial isolation. Of those 65.82% swabs with bacterial
growth, 34.3% of swabs yielded a mixed bacterial population while 31.52% yielded
one type of bacterial growth. The frequency of bacterial isolation from hatch
debris (60%-75%) increased with the age of broiler breeders. MALDI-TOF MS was
able to provide genus-level identification of 83.13% of isolates among all
bacterial types isolated. MALDI-TOF MS identified Enterococcus and Escherichia
coli isolates with 97.18% and 100% accuracy at species level, respectively,
whereas Staphylococcus species were identified with 62.59% accuracy. The
congruence between MALDI-TOF MS identification and 16S rRNA or cpn60 universal
gene target sequencing was 100% or 90%, respectively. Of all bacteria isolated,
Enterococcus species (29.71%) were the most prevalent, followed by E. coli
(19.46%). About 56% of E. coli-infected samples were coinfected with Enterococcus
species. Among all Enterococcus species isolated, Enterococcus faecalis (79.58%)
was the most prevalent, followed by Enterococcus faecium (8.1%). Overall, our
study showed that Enterococcus-associated embryo mortality was predominant in all
three hatcheries investigated and suggests that MALDI-TOF MS technology can be
applied to identify bacteria such as Enterococcus species isolated from poultry.
PMID- 29337629
TI - Biotech crop planting resumes high adoption in 2016.
AB - The global area of biotech crops in 2016 increased from 179.7 million hectares to
185.1 million hectares, a 3% increase equivalent to 5.4 million hectares. Some 26
countries planted biotech crops, 19 of which were developing countries and seven
were industrial. Information and data collected from various credible sources
showed variations from the previous year. Fluctuations in biotech crop area (both
increases and decreases) are influenced by factors including, among others,
acceptance and commercialization of new products, demand for meat and livestock
feeds, weather conditions, global market price, disease/pest pressure, and
government's enabling policies. Countries which have increased biotech crop area
in decreasing order in 2016 were Brazil, United States of America, Canada, South
Africa, Australia, Bolivia, Philippines, Spain, Vietnam, Bangladesh, Colombia,
Honduras, Chile, Sudan, Slovakia, and Costa Rica. Countries with decreased
biotech area in decreasing order were China, India, Argentina, Paraguay, Uruguay,
Mexico, Portugal, and Czech Republic, in decreasing incremental decrease in
biotech area. Pakistan and Myanmar were the only countries with no change in
biotech crop (cotton) planted. Information detailed in the paper including future
crops and traits in each country could guide stakeholders in informed crafting of
strategies and policies for increased adoption of biotech crops in the country.
PMID- 29337630
TI - Ethnic differences in craniofacial and upper spine morphology in children with
skeletal Class II malocclusion.
AB - OBJECTIVES: To analyze differences in upper cervical spine and craniofacial
morphology, including posterior cranial fossa and growth prediction signs,
between Danish and South Korean pre-orthodontic skeletal Class II children and to
analyze associations between upper cervical spine morphology and craniofacial
characteristics. MATERIALS AND METHODS: One hundred forty-six skeletal Class II
children-93 Danes (54 boys and 39 girls, mean age 12.2 years) and 53 Koreans (27
boys and 26 girls, mean age 10.8 years)-were included. Upper spine morphology,
Atlas dimensions, and craniofacial morphology, including posterior cranial fossa
and growth prediction signs, were assessed on lateral cephalograms. Differences
and associations were analyzed by multiple linear and logistic regression
analyses adjusted for age and gender. RESULTS: Significant differences between
the ethnic groups were found in the sagittal and vertical craniofacial dimensions
( P < .001), mandibular shape ( P < .01), dental relationship ( P < .01),
posterior cranial fossa ( P < .05), and growth prediction signs ( P < .001). No
significant differences were found in upper spine morphology and Atlas dimensions
between the groups. Upper spine morphology/dimensions were significantly
associated with the cranial base angle ( P < .01), sagittal craniofacial
dimensions ( P < .001), posterior cranial fossa ( P < .001), and growth
prediction signs ( P < .05). CONCLUSIONS: Upper spine morphology/dimensions may
be valuable as predictive factors in treatment planning for growing Class II
children.
PMID- 29337631
TI - The cervical vertebral maturation method: A user's guide.
AB - The cervical vertebral maturation (CVM) method is used to determine the
craniofacial skeletal maturational stage of an individual at a specific time
point during the growth process. This diagnostic approach uses data derived from
the second (C2), third (C3), and fourth (C4) cervical vertebrae, as visualized in
a two-dimensional lateral cephalogram. Six maturational stages of those three
cervical vertebrae can be determined, based on the morphology of their bodies.
The first step is to evaluate the inferior border of these vertebral bodies,
determining whether they are flat or concave (ie, presence of a visible notch).
The second step in the analysis is to evaluate the shape of C3 and C4. These
vertebral bodies change in shape in a typical sequence, progressing from
trapezoidal to rectangular horizontal, to square, and to rectangular vertical.
Typically, cervical stages (CSs) 1 and CS 2 are considered prepubertal, CS 3 and
CS 4 circumpubertal, and CS 5 and CS 6 postpubertal. Criticism has been rendered
as to the reproducibility of the CVM method. Diminished reliability may be
observed at least in part due to the lack of a definitive description of the
staging procedure in the literature. Based on the now nearly 20 years of
experience in staging cervical vertebrae, this article was prepared as a "user's
guide" that describes the CVM stages in detail in attempt to help the reader use
this approach in everyday clinical practice.
PMID- 29337632
TI - The usefulness of cone-beam computed tomography gray values for alveolar bone
linear measurements.
AB - OBJECTIVES: To test a proof-of-concept that the accuracy and reliability of
alveolar bone height measurements from orthodontic grade (large field-of-view
[FOV], large voxel-size) cone-beam computed tomography (CBCT) images may be
improved by using pixel gray values. MATERIALS AND METHODS: Twenty fresh cadaver
pig heads underwent CBCT scans (17 * 23 cm FOV, 0.4-mm voxel size). Buccal
alveolar bone heights of maxillary first molars were measured using the
conventional vision-based (VB) and the proposed gray value-assisted (GVA)
methods. The GVA methods entailed localization of landmarks through observation
of gray value pattern changes across tissue boundaries followed by mathematical
calculation of distances between landmark pixels. Interrater reliability and
accuracy of CBCT measurements made by all methods were statistically analyzed by
comparing with physical measurements (gold standards). RESULTS: The interrater
reliability of CBCT measurements made by GVA methods was comparable to physical
measurements but higher than those made by the VB method. The GVA (bend-down
pattern) method yielded average measurements similar to physical measurements,
while those obtained by the VB and the GVA (straight pattern) methods were
significantly larger (repeated measures analysis of variance, P < .001). The GVA
(bend-down pattern) method also produced significantly more measurements within
one voxel size of physical measurements than did the VB and GVA (straight
pattern) methods (Chi-square tests, P < .017). CONCLUSIONS: These data confirm a
concept that local gray value change patterns may be used to improve the accuracy
and reliability of alveolar bone height measurement from large FOV and large
voxel-size CBCT images.
PMID- 29337633
TI - Three-dimensional evaluation of maxillary dentoalveolar changes and airway space
after distalization in adults.
AB - OBJECTIVES: To evaluate the changes in position of the maxillary dentition and
the airway space after distalization using a modified C-palatal plate (MCPP) in
adult patients through CBCT images and to analyze the relationship between the
amount of distalization and the changes in the airway space. MATERIALS AND
METHODS: CBCT images of 33 adult Class II patients (22.2 +/- 4.0 years old; 27
women and 6 men) treated by total maxillary arch distalization using the MCPP
were evaluated before and after distalization. The patients were divided into
nonextraction and extraction groups. The changes in the airway space as well as
the changes in the positions of the maxillary dentition were evaluated. The
distalization effects were calculated and assessed using paired t-tests. RESULTS:
After distalization, the first molar showed significant distalization and
intrusion ( P < .001) with no significant rotation of the crown and no
significant buccal displacement of its root in the transverse dimension. There
were no significant changes in the airway volume or the minimum cross-sectional
area of the oropharynx. CONCLUSIONS: The application of the MCPP resulted in
significant total arch distalization without a significant effect on the
transverse dimensions or changes in the oropharynx airway space. The MCPP can be
considered a viable treatment option for patients with Class II malocclusion.
PMID- 29337634
TI - Risk factors associated with open gingival embrasures after orthodontic
treatment.
AB - OBJECTIVES: To investigate the incidence of and contributing factors to open
gingival embrasures between the central incisors after orthodontic treatment.
MATERIALS AND METHODS: One hundred posttreatment patients (29 men and 71 women;
mean age, 24.7 years) were divided retrospectively into occurrence and
nonoccurrence groups based on intraoral photographs. Based on the severity, the
occurrence group was further divided into mild, moderate, and severe groups.
Parameters from periapical radiographs, superimposed lateral cephalograms, and
study models were compared between the occurrence and the nonoccurrence groups by
using independent t-tests and were also analyzed on the basis of severity via
analysis of variance. Logistic regression analysis was performed to identify the
contributing factors to open gingival embrasures. RESULTS: The incidence of open
gingival embrasures between the central incisors was 22% and 36% in the maxilla
and the mandible, respectively. Lingual movement of the incisors, distance from
the contact point to the alveolar crest after treatment, antero-posterior overlap
of the two central incisors before treatment in the maxilla, and distance from
the contact point to the alveolar crest after treatment in the mandible were
significantly associated with the occurrence of open gingival embrasures ( P <
.05). In the mandible, the amount of intrusion was significantly related to
severity ( P < .05). CONCLUSIONS: The incidence of open gingival embrasures
following orthodontic tooth movement is high. Therefore, attention should be paid
to the contributing factors to prevent or reduce the occurrence of open gingival
embrasures.
PMID- 29337635
TI - Reply to M. Horiguchi et al.
PMID- 29337636
TI - New-Onset Cardiovascular Morbidity in Older Adults With Stage I to III Colorectal
Cancer.
AB - Purpose We sought to determine the long-term risk of cardiovascular disease (CVD)
stroke and myocardial infarction-and congestive heart failure (CHF) in older
patients with colorectal cancer, as well as to understand the roles that
preexisting comorbidities and cancer therapy play in increasing this risk.
Patients and Methods We evaluated individuals from the SEER-Medicare database
with incident stage I to III colorectal cancer at age older than 65 years between
January 1, 2000, and December 31, 2011 (n = 72,408) and compared these patients
with a matched cohort of Medicare patients without cancer (n = 72,408). Results
Median age at diagnosis of colorectal cancer was 78 years (range, 66 years to 106
years), and median follow-up was 8 years since diagnosis. The 10-year cumulative
incidence of new-onset CVD and CHF were 57.4% and 54.5% compared with 22% and 18%
for control, respectively ( P < .001). The interaction between hypertension and
chemotherapy was significant ( P < .001) for CVD, and that between diabetes and
chemotherapy was significant ( P < .001) for CHF. Within the first 2 years since
diagnosis, exposure to capecitabine alone increased CHF hazard (hazard ratio
[HR], 3.6; 95% CI, 12.76 to 4.38) compared with exposure to fluorouracil alone.
Conversely, patients who were treated with fluorouracil alone had a higher CVD
hazard at < 2 years and > 2 years since diagnosis compared with patients who
received capecitabine alone (< 2 years HR, 0.63; 95% CI, 0.53 to 0.75; > 2 years
HR, 0.72; 95% CI, 0.62 to 0.84). Conclusion Older patients with colorectal cancer
are at increased risk of developing CVD and CHF. Diabetes and hypertension
interact with chemotherapy to increase the risk of cardiovascular morbidity.
Future studies should assess the potential for personalized therapeutic options
for those with preexisting morbidities and for structured monitoring for patients
with a history of exposure to chemotherapy regimens, as well as explore the
management of preexisting comorbidities to address long-term cardiovascular
morbidity.
PMID- 29337637
TI - Tumor Mutation Burden: Leading Immunotherapy to the Era of Precision Medicine?
PMID- 29337638
TI - Patients With Advanced Melanoma Who Discontinued Treatment With Nivolumab and
Ipilimumab as a Result of Adverse Events Lived Significantly Longer Than Patients
Who Continued Treatment.
PMID- 29337639
TI - Reply to M. Horiguchi et al.
PMID- 29337641
TI - Strain-Specific Symbiotic Genes: A New Level of Control in the Intracellular
Accommodation of Rhizobia Within Legume Nodule Cells.
AB - This is a short commentary on the article by Wang et al. published in MPMI Vol.
31, No. 2, pages 240-248.
PMID- 29337640
TI - Molecular Determinants of Response to Anti-Programmed Cell Death (PD)-1 and Anti
Programmed Death-Ligand 1 (PD-L1) Blockade in Patients With Non-Small-Cell Lung
Cancer Profiled With Targeted Next-Generation Sequencing.
AB - Purpose Treatment of advanced non-small-cell lung cancer with immune checkpoint
inhibitors (ICIs) is characterized by durable responses and improved survival in
a subset of patients. Clinically available tools to optimize use of ICIs and
understand the molecular determinants of response are needed. Targeted next
generation sequencing (NGS) is increasingly routine, but its role in identifying
predictors of response to ICIs is not known. Methods Detailed clinical annotation
and response data were collected for patients with advanced non-small-cell lung
cancer treated with anti-programmed death-1 or anti-programmed death-ligand 1
[anti-programmed cell death (PD)-1] therapy and profiled by targeted NGS (MSK
IMPACT; n = 240). Efficacy was assessed by Response Evaluation Criteria in Solid
Tumors (RECIST) version 1.1, and durable clinical benefit (DCB) was defined as
partial response/stable disease that lasted > 6 months. Tumor mutation burden
(TMB), fraction of copy number-altered genome, and gene alterations were compared
among patients with DCB and no durable benefit (NDB). Whole-exome sequencing
(WES) was performed for 49 patients to compare quantification of TMB by targeted
NGS versus WES. Results Estimates of TMB by targeted NGS correlated well with WES
(rho = 0.86; P < .001). TMB was greater in patients with DCB than with NDB ( P =
.006). DCB was more common, and progression-free survival was longer in patients
at increasing thresholds above versus below the 50th percentile of TMB (38.6% v
25.1%; P < .001; hazard ratio, 1.38; P = .024). The fraction of copy number
altered genome was highest in those with NDB. Variants in EGFR and STK11
associated with a lack of benefit. TMB and PD-L1 expression were independent
variables, and a composite of TMB plus PD-L1 further enriched for benefit to
ICIs. Conclusion Targeted NGS accurately estimates TMB and elevated TMB further
improved likelihood of benefit to ICIs. TMB did not correlate with PD-L1
expression; both variables had similar predictive capacity. The incorporation of
both TMB and PD-L1 expression into multivariable predictive models should result
in greater predictive power.
PMID- 29337642
TI - Perineural Invasion in Parotid Gland Malignancies.
AB - Objectives To investigate the clinical predictors and survival implications of
perineural invasion (PNI) in parotid gland malignancies. Study Design Case series
with chart review. Setting Tertiary care medical center. Subjects and Methods
Patients with parotid gland malignancies treated surgically from 2000 to 2015
were retrospectively identified in the Head and Neck Cancer Registry at a single
institution. Data points were extracted from the medical record and original
pathology reports. Results In total, 186 patients with parotid gland malignancies
were identified with a mean follow-up of 5.2 years. Salivary duct carcinoma (45),
mucoepidermoid carcinoma (44), and acinic cell carcinoma (26) were the most
common histologic types. A total of 46.2% of tumors were found to have PNI. At
the time of presentation, facial nerve paresis (odds ratio [OR], 64.7; P < .001)
and facial pain (OR, 3.7; P = .002) but not facial paresthesia or anesthesia (OR,
2.8, P = .085) were predictive of PNI. Malignancies with PNI were significantly
more likely to be of advanced T and N classification, be high-risk pathologic
types, and have positive margins and angiolymphatic invasion. PNI positivity was
associated with worse overall (hazard ratio, 2.62; P = .001) and disease-free
survival (4.18; P < .001) on univariate Cox regression analysis. However, when
controlling for other negative prognosticators, age, and adjuvant therapy, PNI
did not have a statistically significant effect on disease-free or overall
survival. Conclusions PNI is strongly correlated with more aggressive parotid
gland malignancies but is not an independent predictor of worse survival. Facial
paresis and pain were predictive of PNI positivity, and facial paresis correlated
with worse overall and disease-free survival.
PMID- 29337645
TI - Conservative Approach for Treatment of Maxillary Lateral Incisor Agenesis With
the Deciduous Tooth Retained: 18-Month Follow-Up.
AB - This case describes a female patient with agenesis of the maxillary right lateral
incisor, with her permanent canine in its position and the deciduous canine
retained. Additionally, she presented with a maxillary left peg lateral incisor.
To solve her functional and esthetic complaints, a multidisciplinary approach
involving perio-restorative procedures was proposed. Periodontal surgeries were
performed to align the gingival contour, and the restorative approach utilized
ceramic veneers. At the 18-month clinical and radiographic follow-up, the
treatment outcome was stable, with maintenance of the clinical results achieved
and without any sign of deciduous tooth resorption.
PMID- 29337643
TI - Models for predicting the evolution of influenza to inform vaccine strain
selection.
AB - Influenza vaccine composition is reviewed before every flu season because
influenza viruses constantly evolve through antigenic changes. To inform vaccine
updates, laboratories that contribute to the World Health Organization Global
Influenza Surveillance and Response System monitor the antigenic phenotypes of
circulating viruses all year round. Vaccine strains are selected in anticipation
of the upcoming influenza season to allow adequate time for production. A
mismatch between vaccine strains and predominant strains in the flu season can
significantly reduce vaccine effectiveness. Models for predicting the evolution
of influenza based on the relationship of genetic mutations and antigenic
characteristics of circulating viruses may inform vaccine strain selection
decisions. We review the literature on state-of-the-art tools and prediction
methodologies utilized in modeling the evolution of influenza to inform vaccine
strain selection. We then discuss areas that are open for improvement and need
further research.
PMID- 29337644
TI - Performance of Monolithic and Veneered Zirconia Crowns After Endodontic Treatment
and Different Repair Strategies.
AB - OBJECTIVES: To investigate failure loads of monolithic and veneered all-ceramic
crowns after root canal treatment and to analyze marginal integrity of repair
fillings. METHODS AND MATERIALS: Seventy-two human molars were restored with
monolithic (Zr-All) or veneered (Zr-Ven) zirconia crowns. Molars were assigned to
six groups (n=12 per group) depending on restoration material, access type (no
access cavity [control] or endodontic treatment [test]), and type of filling (one
step [1-st] or two-step [2-st]). For type of filling, molars were treated using a
self-etch universal adhesive and cavities were either filled with layered
composite (1-st) or filled until the crown material was reached, which was
additionally conditioned and then filled (2-st). Scanning electron microscopic
analysis of the restoration margins was performed before and after
thermomechanical loading (TML), and the percentage of continuous margins was
assessed. Crowns were then loaded to failure. RESULTS: Preparation of the access
cavity required more time in monolithic (445 s) than in veneered crowns (342 s).
Loads to failure were higher in control groups (Zr-All: 5814 N; Zr-Ven: 2133 N)
and higher in monolithic test (2985 N) than in veneered test crowns (889 N). In
monolithic crowns, 1-st had lower fracture loads than 2-st fillings (2149 N vs
3821 N). Continuous margins of 66% to 71% were achieved, which deteriorated after
TML by 39% to 40% in Zr-All, by 34% in Zr-Ven-1-st, and by 24% in Zr-Ven-2-st.
CONCLUSIONS: Endodontic access and adhesive restorations resulted in reduced
fracture load in monolithic and veneered zirconia crowns. Two-step fillings
provided higher fracture loads in Zr-All and better marginal quality in Zr-Ven
crowns.
PMID- 29337646
TI - Stability of an aluminum salt-adjuvanted protein D-conjugated pneumococcal
vaccine after exposure to subzero temperatures.
AB - Accidental exposure of a vaccine containing an aluminum-salt adjuvant to
temperatures below 0 degrees C in the cold chain can lead to freeze damage. Our
study evaluated the potential for freeze damage in a licensed aluminum-salt
containing protein-D-conjugated pneumococcal vaccine (PHiD-CV; Synflorix, GSK) in
conditions that included static storage, single subzero-temperature excursions,
and simulated air-freight transportation. Several parameters were assessed
including freezing at subzero temperatures, aluminum-salt-particle size, antigen
integrity and immunogenicity in the mouse. The suitability of the WHO's shake
test for identifying freeze-damaged vaccines was also assessed. During subzero
temperature excursions, the mean temperatures at which PHiD-CV froze (-16.7
degrees C to -18.1 degrees C) appeared unaffected by the type of vaccine
container (two-dose or four-dose vial, or single-dose syringe), vaccine batch,
rotational agitation, or the rate of temperature decline (-0.5 to -10 degrees
C/hour). At constant subzero temperature and in simulated air-freight
transportation, the freezing of PHiD-CV appeared to be promoted by vibration. At
5 degrees C, no PHiD-CV sample froze in static storage (>1 month), whereas when
subjected to vibration, a minority of samples froze (7/21, 33%) within 18 hours.
At -8 degrees C with vibration, nearly all (5/6, 83%) samples froze. In these
vibration regimes, the shake test identified most samples that froze (10/12, 93%)
except two in the -5 degrees C regime. Nevertheless, PHiD-CV-antigen integrity
appeared unaffected by freezing up to -20 degrees C or by vibration. And although
aluminum-salt-particle size was increased only by freezing at -20 degrees C, PHiD
CV immunogenicity appeared only marginally affected by freezing at -20 degrees C.
Therefore, our study supports the use of the shake test to exclude freeze-damaged
PHiD-CV in the field.
PMID- 29337647
TI - Compositional Assessment of Human Tracheal Cartilage by Infrared Spectroscopy.
AB - Objectives To assess the potential of infrared fiber-optic spectroscopy to
evaluate the compositional properties of human tracheal cartilage. Study Design
Laboratory-based study. Methods Twenty human cadaveric distal tracheas were
harvested (age range 20-78 years; 6 females, 14 males) for compositional
analysis. Histologic staining, Fourier transform infrared imaging spectroscopy
data on collagen and proteoglycan (PG) content, and near-infrared (NIR) fiber
optic probe spectroscopic data that reflect protein and water content were
evaluated. NIR fiber-optic probe data were also obtained from the proximal
trachea in 4 human cadavers (age range 51-65 years; 2 females, 2 males) in situ
for comparison to distal trachea spectral data. Results In the distal trachea
cohort, the spectroscopic-determined ratio of PG/amide I, indicative of the
relative amount of PG, was significantly higher in the tissues from the younger
group compared to the older group (0.37 +/- 0.08 vs 0.32 +/- 0.05, P = .05). A
principal component analysis of the NIR spectral data enabled separation of
spectra based on tracheal location, likely due to differences in both protein and
water content. The NIR-determined water content based on the 5200-cm-1 peak was
significantly higher in the distal trachea compared to the proximal trachea ( P <
.001). Conclusions Establishment of normative compositional values and further
elucidating differences between the segments of trachea will enable more directed
research toward appropriate compositional end points in regenerative medicine for
tracheal repair.
PMID- 29337648
TI - Simultaneous amplification of exons 18 to 21 of the EGFR gene using 5' tailed
primers and a two-stage protocol.
AB - OBJECTIVE: Reduction of non-specific amplification and achievement of efficient
amplification of multiple gene fragments under the same reaction condition is the
basic goal of PCR diagnosis; however, this is often difficult. This study was
conducted to establish a highly specific and effective amplification of the
epidermal growth factor receptor (EGFR) gene's exons, 18-21, simultaneously.
METHODS: The 5'-tailed primers were synthesized by adding 10 to 20 bp of a non
specific sequence to the 5'-terminus of sequence-specific primers (tailless
primers). The two-stage protocol consisted of 5-10 cycles of a conventional 3
step cycling, which was then followed by 30-35 cycles of two-step cycling. The
exons 18-21 of EGFR gene were amplified in 28 non-small cell lung cancer (NSCLC)
patients using an optimized PCR that combined 5' tailed primers with a two-stage
protocol. RESULTS: The 5' tailed primers exhibited a wider range of suitable
annealing temperatures, similar range of primer concentration, similar
sensitivity, specificity, and reproducibility, as well as a reduced, non-specific
amplification compared with the corresponding tailless primers. The amplification
of exons 18-21 of EGFR gene in NSCLC patients revealed that a combination of 5'
tailed primers with two-stage protocol (optimized PCR) had a similar PCR success
rate (P = 0.873) but had significantly reduced non-specific amplification (P
<0.001) compared to conventional PCR. CONCLUSION: 5' tailed primers exhibited a
wider range of suitable annealing temperatures and improved specificity compared
with conventional PCR primers. An optimized PCR was established with 5' tailed
primers and a two-stage protocol to amplify exons 18-21 of the EGFR gene in NSCLC
patients.
PMID- 29337649
TI - Neurocognitive Deficits Associated With ADHD in Athletes: A Systematic Review.
AB - CONTEXT: Attention deficit hyperactivity disorder (ADHD) is a common childhood
disorder and is frequently diagnosed in young adults. Emerging studies suggest a
relationship between ADHD and concussion. OBJECTIVE: To determine whether
athletes with ADHD are at increased risk for neurocognitive deficits related to
concussion risk, symptom reporting, and recovery. DATA SOURCES: A comprehensive
search of PubMed, CINAHL, PsychInfo, and Cochrane Library databases was
performed. Studies conducted between 2006 and 2017 were reviewed, although only
those between 2013 and 2017 met inclusion criteria. STUDY SELECTION: Studies that
examined neurocognitive deficits in adolescent and young adult athletes aged 15
to 19 years who had ADHD and reported using notable neuropsychological evaluation
tools were included. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 2.
RESULTS: A total of 17 studies met the inclusion criteria. The prevalence of ADHD
in athletes varied between 4.2% and 8.1%. Overall, athletes with ADHD
demonstrated lower scores on neurocognitive testing such as the ImPACT (Immediate
Post-Concussion Assessment and Cognitive Test), increased risk for concussion,
and increased symptom reporting. There was no evidence that treatment with
stimulant medication changed these risks. CONCLUSION: ADHD is associated with
increased neurocognitive deficits in athletes, although pathophysiology remains
unclear. Evidence for stimulant treatment in athletes with ADHD continues to be
sparse.
PMID- 29337650
TI - The Association of External Transfer Status with Adverse Outcomes in
Otolaryngology.
AB - Objective To compare rates of morbidity and mortality in patients treated by
otolaryngologists who undergo interhospital transfers vs those who do not and to
quantify conditions requiring interhospital transfers in this population. Study
Design Cohort study. Setting American College of Surgeons National Surgical
Quality Improvement Program. Subjects and Methods We identified patients
requiring surgery by otolaryngologists in the National Surgical Quality
Improvement Program database from 2006 to 2013. We compared patients who were
transferred from an outside institution to those admitted from home. Multivariate
regression was used to adjust for patient characteristics, comorbidities, and
case mix. The primary outcome was overall morbidity and mortality within 30 days
of surgery. Results We identified 60,498 patients; 488 (0.8%) were transferred
from another institution. Operations that were more common in the transferred
group were incision and drainage (24.0% vs 1.2%), facial trauma repair (9.0% vs
3.1%), and oropharyngeal hemorrhage control (3.9% vs 0.4%). External transfer
patients had significantly longer hospital stays (44.1% vs 4.4% >7 days, P <
.05). On unadjusted analysis, transferred patients had a significantly higher
rate of morbidity and mortality (odds ratio [OR], 11.3; 95% confidence interval
[CI], 9.4-13.5). On multivariate analysis, transferred patients had a
significantly greater rate of morbidity and mortality (OR, 3.1; 95% CI, 2.4-4.0).
Conclusion Transfer from another institution is associated with worse outcomes
independent of case mix, demographics, and preoperative comorbidities in acute
otolaryngology conditions requiring surgery. Practitioners should be aware of
this when caring for transfer patients, and transfer status should be considered
when measuring hospital quality.
PMID- 29337651
TI - The effects of booster vaccination of hepatitis B vaccine on children 5-15 years
after primary immunization: A 5-year follow-up study.
AB - The aim of this study was to evaluate changes in hepatitis B surface antibody
titers (anti-HBs) after booster vaccinations in children aged 5-15 y and to
provide suitable immunization strategies. A total of 2208 children were initially
enrolled in screening, and 559 children were finally included. The participants
were divided into 2 groups according to their pre-booster anti-HBs levels: Group
I, <10 mIU/ml and Group II, >=10 mIU/ml. Group I was administered 3 doses of
booster hepatitis B vaccine (0-1-6 months, 10 MUg), and Group II was administered
1 dose of booster hepatitis B vaccine (10 MUg). The antibody titer changes were
examined at 4 time points: 1 month after dose 1 and dose 3, and 1 year and 5
years after dose 3. The protective seroconversion rates at those points were
95.65%, 99.67%, 97.59% and 91.05% (p < 0.001), respectively, in Group I, and
100.00%, 99.87%, 99.66% and 98.21% (chi2 = 6.04, p = 0.11), respectively, in
Group II. The GMT in subjects aged 5-9 y were higher than that in subjects aged
10-15 y in both Group I and Group II at 1 month after dose 1, but no difference
was observed at the other three time points. This study demonstrates that booster
vaccination has a good medium-term effect. A booster dose for subjects with
protective antibodies is not necessary but effective, and 3 doses of hepatitis B
vaccination are recommended for those who have lost immunological memory.
Receiving booster immunization at the age of 10-15 years may be more appropriate
for individuals living in HBV high epidemic areas.
PMID- 29337652
TI - Poorly neutralizing polyclonal antibody in vitro against coxsackievirus A16
circulating strains can prevent a lethal challenge in vivo.
AB - Neutralizing antibodies (NTAbs) is a major criterion for evaluation the
immunogenicity of many vaccines, for example, poliovirus and EV71 vaccine. Here,
we firstly discovered that polyclonal antibodies induced by inactivated CVA16
vaccine and lived CVA16 virus have poor ability to neutralize circulating CVA16
strains in vitro. However, the passive transfer of poorly neutralizing polyclonal
antibodies can protect suckling mice from lethally challenged with circulating
strains in vivo. In addition, the obvious dose response was found between the
titer of antibodies and the survival rate. Interestingly, poorly neutralizing
polyclonal antibodies against circulating CVA16 strains, have good ability to
neutralize prototype strain G10 in vitro. Between G10 and circulating CVA16
strains, there are total 47 variant sites in capsid, which are near the interface
of VP1, VP2, and VP3, and close to 2-fold axis. Based on the structure of CVA16,
the obvious structural changes were observed in residue 213 of VP1 GH loop,
residue 139 of VP2 EF loop, and residues 59, 182 and 183 of VP3 GH loop. What we
found may provide a new sight for the development of CVA16 vaccine.
PMID- 29337653
TI - Safety and immunogenicity of a meningococcal B recombinant vaccine when
administered with routine vaccines to healthy infants in Taiwan: A phase 3, open
label, randomized study.
AB - Neisseria meningitidis is associated with high mortality and morbidity in infants
and children worldwide. This phase 3 study (NCT02173704) evaluated safety and
immunogenicity of a 4-component serogroup B recombinant meningococcal vaccine
(4CMenB) co-administered with routine vaccines in Taiwanese infants. In total,
225 healthy infants were randomized (2 : 1 ) to receive 4CMenB and routine
vaccines (4CMenB+Routine) or routine vaccines only (Routine group) at 2, 4, 6 and
12 months of age. Routine vaccines were diphtheria-tetanus-acellular pertussis
inactivated poliovirus-Haemophilus influenzae type b, 13-valent pneumococcal,
hepatitis B, measles-mumps-rubella and varicella vaccines. Immune responses to
4CMenB components (factor H binding protein [fHbp], Neisserial adhesin A [NadA],
porin A [PorA] and Neisseria heparin-binding antigen [NHBA]) were evaluated at 1
month post-primary and post-booster vaccination, using human serum bactericidal
assay (hSBA). Reactogenicity and safety were also assessed. A sufficient immune
response was demonstrated for fHbp, NadA and PorA, at 1 month post-primary and
booster vaccination. In the 4CMenB+Routine group, hSBA titers >=5 were observed
in all infants for fHbp and NadA, in 79% and 59% of infants for PorA and NHBA,
respectively, at 1 month post-primary vaccination and in 92-99% of infants for
all antigens, at 1 month post-booster vaccination. In the 4CMenB+Routine group,
hSBA geometric mean titers for all antigens increased post-primary (8.41-963) and
post-booster vaccination (17-2315) compared to baseline (1.01-1.36).
Immunogenicity of 4CMenB was not impacted by co-administration with routine
pediatric vaccines in infants. Reactogenicity was slightly higher in the
4CMenB+Routine group compared with Routine group, but no safety concerns were
identified.
PMID- 29337654
TI - Oral Antihistamines Alone vs in Combination with Leukotriene Receptor Antagonists
for Allergic Rhinitis: A Meta-analysis.
AB - Objective To evaluate whether an adjuvant therapy of leukotriene receptor
antagonists (LTRAs) based on oral H1-antihistamines (H1) can increase efficacy of
allergic rhinitis (AR) treatment. Data Sources The search involved databases of
PubMed, EMBASE, and Cochrane Central Register of Controlled Trials, from
inception up to September 23, 2017. Randomized controlled trials (RCTs) that
compared efficacy of LTRAs + H1 vs H1 alone were eligible. Review Methods Pooled
comparative effects were measured using weighted mean difference (WMD) and 95%
confidence interval (CI). Subgroup analysis comparing seasonal vs perennial AR
was prespecified to explore the source of heterogeneity. The evidence quality of
each outcome was assessed by the GRADE approach. Results A total of 8 RCTs were
included (n = 1886), and all measured outcomes used scaled scores. Compared with
H1 alone, H1 + LTRAs were superior to improve overall daytime (WMD, -0.11; 95%
CI, -0.19 to -0.03, high quality) and composite (WMD, -0.12; 95% CI, -0.23 to
0.01; low quality) nasal symptoms. Specifically, H1 + LTRAs had better efficacy
against composite nasal rhinorrhea, sneezing, and daytime itching but not
congestion. The effects were more pronounced in patients with perennial AR
compared to those with seasonal AR. There were no significant differences in
nighttime nasal symptoms and eye symptoms between the 2 groups. Conclusion The
current evidence suggests that LTRAs + H1 can increase the therapeutic efficacy
against daytime and composite nasal symptoms, including rhinorrhea, sneezing, and
itching; however, it does not affect nighttime nasal symptoms and eye symptoms.
The patients with perennial AR may benefit more from the combination therapy.
PMID- 29337655
TI - The Patient Who Continues to Smoke On-Treatment: An Ethical Dilemma.
PMID- 29337656
TI - A review of methodology for the analysis of pyrethrin and pyrethroid residues in
food of animal origin.
AB - Pyrethrin and pyrethroid pesticides are commonly used in crop protection and
animal health, to control pests. As a result, they can potentially transfer into
food if good agricultural practice is not followed or even due to accidental
contamination. The analysis of these compounds has been widely reported in crops
and the environment. However, the analysis of pyrethrin and pyrethroids has not
been reported frequently in foods of animal origin, particularly animal tissues.
The focus of this review is to report on pyrethrin and pyrethroid analysis
including key aspects such as chemistry, choice of target matrix, sample
preparation, chemical analysis, legislation and method validation. This review
shows that most methodologies for the analysis of these compounds are based on
gas chromatography with the trend in recent years to move towards GC-MS or GC
MS/MS based platforms. This review shows that these compounds can also be
satisfactorily analysed by LC-MS/MS, which can be advantageous because of shorter
chromatographic run times. A wide range of sample preparation procedures have
been applied in analytical methods and more complex protocols are required for GC
applications, whereas more crudely prepared extracts can be analysed by LC-MS/MS.
This review demonstrates that pyrethrin and pyrethroid residues should be
included as analytes in multi-class analytical methods for pesticides and
veterinary drug residues in animal derived foods.
PMID- 29337657
TI - The prevalence of deoxynivalenol and its derivatives in the spring wheat grain
from different agricultural production systems in Lithuania.
AB - Deoxynivalenol (DON) together with two acetylated derivatives, 3
acetyldeoxynivalenol (3-ADON) and 15-acetyldeoxynivalenol (15-ADON) occurs in
cereal grains and their products. Co-occurrence of DON and acetylated derivatives
in cereal grain is detected worldwide. Until now, DON and its derivatives have
been considered equally toxic by health authorities. In this study, we analysed
103 samples of spring wheat grain, originating from the fields of different
production systems in Lithuania, for the co-occurrence of type-B trichothecenes
(DON, 3-ADON, 15-ADON). The samples were classified according to the production
system-organic, sustainable and intensive. Mycotoxin levels in the spring wheat
grain samples were determined by the HPLC method with UV detection. The type-B
trichothecenes were found to be present at higher concentrations in the grain
from the intensive production system. Eighty-one percent of the spring wheat
grain samples from the intensive production system were co-contaminated with a
combination of DON+3-ADON+15-ADON, 1% with DON+3-ADON. Additionally, DON+15-ADON
and DON were found in 5% and 10% of the tested samples, respectively. Two percent
of the samples were free from mycotoxins. In the grain samples from the
sustainable production system, DON and a combination of DON+3-ADON showed a
higher incidence - 47% and 23%, respectively. The samples with a combination of
DON+3-ADON+15-ADON accounted for 18%. Completely different results were obtained
from the analyses of organic grain samples. A large number of the organic spring
wheat grain samples were contaminated with DON+3-ADON (55%) or DON (36%). The
combination of DON+3-ADON+15-ADON was not present, while DON+15-ADON was present
in 9% of the samples tested. The production systems did not lead to significant
differences in mycotoxin levels, although a trend toward higher incidence and
higher contamination was observed for the samples from the intensive and
sustainable production systems.
PMID- 29337658
TI - Versicolorin A is a potential indicator of aflatoxin contamination in the granary
stored corn.
AB - The objective of this study was to evaluate the feasibility of the predictive
monitoring of aflatoxin B1 (AFB1) under granary conditions, since mycotoxin
contamination of the stored grain represents an important issue. Using the
storage test, we investigated the relationship between versicolorin A (Ver A, an
intermediate in AFB1 biosynthesis) levels and the levels of aflatoxigenic fungi,
and their relationship with aflatoxin production. All samples, except for one,
were found to be contaminated with aflatoxigenic fungi using PCR analyses, while
their AFB1 levels were not detectable before the storage test using an enzyme
linked immunosorbent assay (ELISA) method with an LOD of 2 MUg/kg. Aflatoxigenic
fungi levels were analysed, as well as Ver A levels prior to the accumulation of
AFB1 (Levels were >=5 MUg/kg; the permissible levels of AFB1 in corn intended for
direct consumption are <5 MUg/kg (EC)). Statistical analyses demonstrated that
aflatoxin levels after both actual storage and safe storage (AFB1?5MUg/kg) times
are significantly correlated with the Ver A levels and the changes in Ver A
levels (DeltaVer A). Both high and variable Ver A levels were indicative of the
vigorous metabolic activity of aflatoxigenic fungi. In contrast, steady Ver A
levels showed that aflatoxin production by the fungi was not active. Monitoring
Ver A levels and their changes may allow an earlier detection of harmful
aflatoxin contamination in the stored grain. Additionally, the toxicity of Ver A
should be further examined. The results of our study indicate that the monitoring
of Ver A levels, even when the AFB1 levels are very low, may increase the safety
of grain consumption, especially considering Ver A toxicity.
PMID- 29337659
TI - Determination of five tetracyclines and their epimers by LC-MS/MS based on a
liquid-liquid extraction with low temperature partitioning.
AB - An LC-MS/MS method is presented for screening five tetracyclines and their
epimers in a broad range of food products. The scope of matrices includes meat-,
fish-, seafood-based products, various dairy ingredients, infant formulae and
fats. The method principle is based on a liquid-liquid extraction with aqueous
ethylenediaminetetraacetic acid (EDTA) and acetonitrile followed by a freezing
step to promote phase separation at low temperature. After defatting with hexane,
sample extracts were evaporated and reconstituted before injection onto the LC
MS/MS system. The addition of oxalic acid in the aqueous mobile phase was
mandatory to maintain good peak shape and sensitivity over the run. The screening
is based upon a double preparation of each sample, one 'as such' and a second one
with the analytes spiked in the sample, in order to mitigate the risk of false
negative response. The method was validated according to the European Community
Reference Laboratories Residues Guidelines. A total of 93 samples were included
in the validation by two independent laboratories giving both false-negative and
false-positive rates at 0% for all compounds. Over the last two years, 2600
samples were analysed routinely and only one chicken sample was found above the
regulatory limit.
PMID- 29337660
TI - Guidance for Evaluating the Safety of Experimental Releases of Mosquitoes,
Emphasizing Mark-Release-Recapture Techniques.
AB - Experimental releases of mosquitoes are performed to understand characteristics
of populations related to the biology, ability to transmit pathogens, and
ultimately their control. In this article, we discuss considerations related to
the safety of experimental releases of living mosquitoes, applying principles of
good practice in vector biology that protect human health and comfort. We
describe specific factors of experimental releases of mosquitoes that we believe
are critical to inform institutional biosafety committees and similar review
boards to which proposals to conduct mosquito release experiments have been
submitted. In this study, "experimental releases" means those that do not
significantly increase vector capacity or nuisance biting relative to the
unperturbed natural baseline. This document specifically does not address
releases of mosquitoes for ongoing control programs or trials of new control
methods for which broader assessments of risk are required. It also does not
address releases of transgenic or exotic (non-native) mosquito species, both of
which require particular regulatory approval. Experimental releases may include
females and males and evaluation must consider their effects based on the number
released, their genotype and phenotype, the environment into which they are
released, and postrelease collection activities. We consider whether increases of
disease transmission and nuisance biting might result from proposed experimental
releases against the backdrop of natural population size variation. We recommend
that experimental releases be conducted in a manner that can be reasonably argued
to have insignificant negative effects. Reviewers of proposals for experimental
releases should expect applicants to provide such an argument based on evidence
from similar studies and their planned activities. This document provides
guidance for creating and evaluating such proposals.
PMID- 29337661
TI - Maintaining Quality of Candidate Strains of Transgenic Mosquitoes for Studies in
Containment Facilities in Disease Endemic Countries.
AB - Transgenic mosquitoes are being developed as novel components of area-wide
approaches to vector-borne disease control. Best practice is to develop these in
phases, beginning with laboratory studies, before moving to field testing and
inclusion in control programs, to ensure safety and prevent costly field testing
of unsuitable strains. The process of identifying and developing good candidate
strains requires maintenance of transgenic colonies over many generations in
containment facilities. By working in disease endemic countries with target
vector populations, laboratory strains may be developed and selected for
properties that will enhance intended control efficacy in the next phase, while
avoiding traits that introduce unnecessary risks. Candidate strains aiming toward
field use must consistently achieve established performance criteria, throughout
the process of scaling up from small study colonies to production of sufficient
numbers for field testing and possible open release. Maintenance of a consistent
quality can be demonstrated by a set of insect quality and insectary operating
indicators, measured over time at predetermined intervals. These indicators:
inform comparability of studies using various candidate strains at different
times and locations; provide evidence of conformity relevant to compliance with
terms of approval for regulated use; and can be used to validate some assumptions
related to risk assessments covering the contained phase and for release into the
environment.
PMID- 29337663
TI - Genetically Engineered Mosquitoes for Pathogen Control.
PMID- 29337662
TI - Studies of Transgenic Mosquitoes in Disease-Endemic Countries: Preparation of
Containment Facilities.
AB - Novel approaches to area-wide control of vector species offer promise as
additional tools in the fight against vectored diseases. Evaluation of transgenic
insect strains aimed at field population control in disease-endemic countries may
involve international partnerships and should be done in a stepwise approach,
starting with studies in containment facilities. The preparations of both new
build and renovated facilities are described, including working with local and
national regulations regarding land use, construction, and biosafety
requirements, as well as international guidance to fill any gaps in regulation.
The examples given are for containment categorization at Arthropod Containment
Level 2 for initial facility design, classification of wastes, and precautions
during shipping. Specific lessons were derived from preparations to evaluate
transgenic (non-gene drive) mosquitoes in West and East African countries.
Documented procedures and the use of a non-transgenic training strain for trial
shipments and culturing were used to develop competence and confidence among the
African facility staff, and along the chain of custody for transport. This
practical description is offered to support other research consortia or
institutions preparing containment facilities and operating procedures in
conditions where research on transgenic insects is at an early stage.
PMID- 29337664
TI - Containment Studies of Transgenic Mosquitoes in Disease Endemic Countries: The
Broad Concept of Facilities Readiness.
AB - Genetic strategies for large scale pest or vector control using modified insects
are not yet operational in Africa, and currently rely on import of the modified
strains to begin preliminary, contained studies. Early involvement of research
teams from participating countries is crucial to evaluate candidate field
interventions. Following the recommended phased approach for novel strategies,
evaluation should begin with studies in containment facilities. Experiences to
prepare facilities and build international teams for research on transgenic
mosquitoes revealed some important organizing themes underlying the concept of
"facilities readiness," or the point at which studies in containment may proceed,
in sub-Saharan African settings. First, "compliance" for research with novel or
non-native living organisms was defined as the fulfillment of all legislative and
regulatory requirements. This is not limited to regulations regarding use of
transgenic organisms. Second, the concept of "colony utility" was related to the
characteristics of laboratory colonies being produced so that results of studies
may be validated across time, sites, and strains or technologies; so that the
appropriate candidate strains are moved forward toward field studies. Third, the
importance of achieving "defensible science" was recognized, including that study
conclusions can be traced back to evidence, covering the concerns of various
stakeholders over the long term. This, combined with good stewardship of
resources and appropriate funding, covers a diverse set of criteria for declaring
when "facilities readiness" has been attained. It is proposed that, despite the
additional demands on time and resources, only with the balance of and rigorous
achievement of each of these organizing themes can collaborative research into
novel strategies in vector or pest control reliably progress past initial
containment studies.
PMID- 29337665
TI - Safety of intravenous tranexamic acid in patients undergoing majororthopaedic
surgery: a meta-analysis of randomised controlled trials.
AB - Among the various pharmacological options to decrease peri-operative bleeding,
tranexamic acid appears to be one of the most interesting. Several trials have
consistently documented the efficacy of this synthetic drug in reducing the risk
of blood loss and the need for allogeneic blood transfusion in patients
undergoing total hip and knee arthroplasty. The safety of intravenous tranexamic
acid in major orthopaedic surgery, particularly regarding the risk of venous
thromboembolism, was systematically analysed in this review. A systematic search
of the literature identified 73 randomised controlled trials involving 4,174
patients and 2,779 controls. The raw overall incidence of venous thromboembolism
was 2.1% in patients who received intravenous tranexamic acid and 2.0% in
controls. A meta-analytic pooling showed that the risk of venous thromboembolism
in tranexamic acid-treated patients was not significantly different from that of
controls (risk difference: 0.01%, 95% confidence interval [CI]: -0.05%, 0.07%;
risk ratio: 1.067, 95% CI: 0.760-1.496). Other severe drug-related adverse events
occurred very rarely (0.1%). In conclusion, the results of this systematic review
and meta-analysis show that intravenous tranexamic acid is a safe pharmacological
treatment to reduce blood loss and transfusion requirements in patients
undergoing major orthopaedic surgery.
PMID- 29337666
TI - Tuning of in vivo cognate B-T cell interactions by Intersectin 2 is required for
effective anti-viral B cell immunity.
AB - Wiskott-Aldrich syndrome (WAS) is an immune pathology associated with mutations
in WAS protein (WASp) or in WASp interacting protein (WIP). Together with the
small GTPase Cdc42 and other effectors, these proteins participate in the
remodelling of the actin network downstream of BCR engagement. Here we show that
mice lacking the adaptor protein ITSN2, a G-nucleotide exchange factor (GEF) for
Cdc42 that also interacts with WASp and WIP, exhibited increased mortality during
primary infection, incomplete protection after Flu vaccination, reduced germinal
centre formation and impaired antibody responses to vaccination. These defects
were found, at least in part, to be intrinsic to the B cell compartment. In vivo,
ITSN2 deficient B cells show a reduction in the expression of SLAM, CD84 or ICOSL
that correlates with a diminished ability to form long term conjugates with T
cells, to proliferate in vivo, and to differentiate into germinal centre cells.
In conclusion, our study not only revealed a key role for ITSN2 as an important
regulator of adaptive immune-response during vaccination and viral infection but
it is also likely to contribute to a better understanding of human immune
pathologies.
PMID- 29337668
TI - Solving manufacturing problems for L-carnitine-L-tartrate to improve the
likelihood of successful product scale-up.
AB - L-carnitine-L-tartrate, a non-essential amino acid, is hygroscopic. This causes a
problem in tablet production due to pronounced adhesion of tablets to punches. A
33 full factorial design was adopted to suggest a tablet formulation. Three
adsorbents were suggested (Aerosil 200, Aerosil R972, talc) to reduce stickiness
at three concentrations (1, 3 and 5 %), and three fillers (mannitol, Avicel PH
101, Dibasic calcium phosphate) were chosen to prepare 27 formulations.
Micromeritic properties of formulations were studied, and tablets were prepared
by wet granulation. Absence of picking, sticking or capping, recording of
sufficient hardness, acceptable friability and tablet ejection force indicated
formulation success. The resulting formulation prepared using Avicel PH 101 and 1
% Aerosil 200 was submitted to further investigation in order to choose the most
suitable compression conditions using a 33 full factorial design. Variables
included compression force, tableting rate and magnesium stearate (lubricant)
concentration. The formulation prepared at compression force of 25 kN, using 2 %
magnesium stearate, at a production rate of 30 tablets/ minute, was found to be
the most appropriate scale up candidate.
PMID- 29337667
TI - Revised roles of ISL1 in a hES cell-based model of human heart chamber
specification.
AB - The transcription factor ISL1 is thought to be key for conveying the multipotent
and proliferative properties of cardiac precursor cells. Here, we investigate its
function upon cardiac induction of human embryonic stem cells. We find that ISL1
does not stabilize the transient cardiac precursor cell state but rather serves
to accelerate cardiomyocyte differentiation. Conversely, ISL1 depletion delays
cardiac differentiation and respecifies nascent cardiomyocytes from a ventricular
to an atrial identity. Mechanistic analyses integrate this unrecognized anti
atrial function of ISL1 with known and newly identified atrial inducers. In this
revised view, ISL1 is antagonized by retinoic acid signaling via a novel player,
MEIS2. Conversely, ISL1 competes with the retinoic acid pathway for prospective
cardiomyocyte fate, which converges on the atrial specifier NR2F1. This study
reveals a core regulatory network putatively controlling human heart chamber
formation and also bears implications for the subtype-specific production of
human cardiomyocytes with enhanced functional properties.
PMID- 29337669
TI - Gastroprotective effects of the isopropanol extract of Artemisia princeps and its
gastroretentive floating tablets on gastric mucosal injury.
AB - In this study, we investigated the gastroprotective effect of an isopropanol
extract from the aerial parts of Artemisia princeps (IPAP) and developed a
gastroretentive floating tablet of IPAP (IPAP-FR) for maximized local
gastroprotective effects. Pre-treatment with IPAP ameliorated the gastric mucosal
hemorrhagic lesions in ethanol/HCl- or indomethacin- treated rats. IPAP decreased
mucosal hemorrhage of gastric ulcers induced by ethanol or indomethacin plus
pyloric ligation in rats. The optimized floating tablet, IPAP-FR, floated on
medium surface with more sustained eupatilin release compared to the non-floating
control tablet. X-ray photographs in beagle dogs showed that IPAPFR was retained
for > 2 h in the stomach. In the ethanol-induced gastric ulcer rat model, the
gastric hemorrhagic lesion was improved more substantially with IPAP-FR compared
to the non-floating control tablet. Based on these data, our data suggest that
IPAP-FR has an improved therapeutic potential for the treatment of gastric ulcer.
PMID- 29337670
TI - Sustained release biodegradable solid lipid microparticles: Formulation,
evaluation and statistical optimization by response surface methodology.
AB - For preparing nebivolol loaded solid lipid microparticles (SLMs) by the solvent
evaporation microencapsulation process from carnauba wax and glyceryl
monostearate, central composite design was used to study the impact of
independent variables on yield (Y1), entrapment efficiency (Y2) and drug release
(Y3). SLMs having a 10-40 MUm size range, with good rheological behavior and
spherical smooth surfaces, were produced. Fourier transform infrared
spectroscopy, differential scanning calorimetry and X-ray diffractometry pointed
to compatibility between formulation components and the zeta-potential study
confirmed better stability due to the presence of negative charge (-20 to -40
mV). The obtained outcomes for Y1 (29-86 %), Y2 (45-83 %) and Y3 (49-86 %) were
analyzed by polynomial equations and the suggested quadratic model were
validated. Nebivolol release from SLMs at pH 1.2 and 6.8 was significantly (p <
0.05) affected by lipid concentration. The release mechanism followed Higuchi and
zero order models, while n > 0.85 value (Korsmeyer- Peppas) suggested slow
erosion along with diffusion. The optimized SLMs have the potential to improve
nebivolol oral bioavailability.
PMID- 29337671
TI - Spectrophotometric method for simultaneous determination of valsartan and
substances from the group of statins in binary mixtures.
AB - Applicability of derivative spectrophotometry for the determination of valsartan
in the presence of a substance from the group of statins was checked. The
obtained results indicate that the proposed method may be effective by using
appropriate derivatives: for valsartan and fluvastatin - D1, D2 and D3, for
valsartan and pravastatin - D1 and D3, for valsartan and atorvastatin - D2 and
D3. The method was characterized by high sensitivity and accuracy. Linearity was
maintained in the following ranges: 9.28-32.48 mg mL-1 for valsartan, 8.16-28.56
mg mL-1 f or fluvastatin, 14.40-39.90 mg mL-1 for atorvastatin and 9.60-48.00 mg
mL-1 for pravastatin. Determination coefficients were in the range of 0.989-0.999
depending on the analyte and the order of derivative. The precision of the method
was high with RSD from 0.1 to 2.5 % and recovery of individual components was
within the range of 100 +/- 5 %. The developed method was successfully applied to
the determination of valsartan combined with fluvastatin, atorvastatin and
pravastatin in laboratory prepared mixtures and in pharmaceutical preparations.
PMID- 29337672
TI - Influence of plasma on the physical properties of ointments with quercetin.
AB - Effects of two independent variables - the content of quercetin (0 or 1 or 1.5 or
5 %) and the content of plasma (0 or 2 or 4 or 6 %) - on the organoleptic
properties and rheological parameters of model formulations prepared on an
amphiphilic base were estimated. The consistency of all ointments was uniform,
and the content of quercetin and plasma lay within the predefined range. Tested
ointments are non-Newtonian systems. The content of quercetin and plasma was
found to have a significant effect on the rheological properties of the
ointments. An increase in the content of plasma in ointments was accompanied by a
significant increase in their hardness, viscosity and shear stress and a
reduction of their spreadability. The best rheological properties were shown by
formulation F-3, containing 1.5 % of quercetin and 2 % of plasma.
PMID- 29337673
TI - Evaluation of immunomodulatory effects of lamotrigine in BALB/c mice.
AB - Modulation of the immune system has recently been shown to be involved in the
pharmacological effects of old antiepileptic drugs and in the pathogenesis of
epilepsy. Therefore, the most recent guidelines for immunotoxicological
evaluation of drugs were consulted to investigate the immunomodulatory effects of
lamotrigine, a newer antiepileptic drug, in BALB/c mice. These included the in
vivo effects of lamotrigine on delayed-type hypersensitivity (DTH) response to
sheep red blood cell (SRBC) antigens, hemagglutination titer assays and
hematological changes. In vitro effects of lamotrigine on ConA-induced splenocyte
proliferation and cytokine secretion were assessed. The results showed that
lamotrigine treatment significantly increased the DTH response to SRBC in the
mouse model of this study. This was accompanied by a significant increase in
relative monocyte and neutrophil counts and in spleen cellularity. Lamotrigine
significantly inhibited ConA-induced splenocyte proliferation in vitro and it
significantly inhibited IL-2 and TNF-alpha secretion in ConA-stimulated
splenocytes. In conclusion, the results demonstrated significant immunomodulatory
effects of lamotrigine in BALB/c mice. These data could expand the understanding
of lamotrigine-induced adverse reactions and its role in modulating the immune
system in epilepsy.
PMID- 29337674
TI - A study on blocking store-operated Ca2+ entry in pulmonary arterial smooth muscle
cells with xyloketals from marine fungi.
AB - In this study, the effect of four xyloketals 1-4 on store-operated calcium entry
(SOCE) was investigated in primary distal pulmonary arterial smooth muscle cells
(PASMCs) isolated from mice. The results showed that xyloketal A (1), an unusual
ketal with C-3 symmetry, exhibited strong SOCE blocking activity. Secretion of
interleukin-8 (IL-8) was also inhibited by xyloketal A. The parallel artificial
membrane permeability assay (PAMPA) of 1-4 suggested that these xyloketals
penetrated easily through the cell membrane. Moreover, the molecular docking
study of xyloketal A with activation region of the stromal interaction molecule
(STIM) 1 and the calcium release-activated calcium modulator (ORAI) 1 (STIM1
ORAI1) protein complex, the key domain of SOCE, revealed that xyloketal A
exhibited a noncovalent interaction with the key residue lysine 363 (LYS363) in
the identified cytosolic regions in STIM1-C. These findings provided useful
information about xyloketal A as a SOCE inhibitor for further evaluation.
PMID- 29337675
TI - Synthesis and evaluation of antitumor activity of new 4-substituted thieno[3,2
d]pyrimidine and thienotriazolopyrimidine derivatives.
AB - 3-Methyl-6-phenyl-2-thioxo-2,3-dihydrothieno[3,2-d]pyrimidin- 4(1H)-one (2), on
treatment with phosphorous oxychoride, affored 4-chloro-3-methyl-6-phenyl
thieno[3,2-d]pyrimidine- 2(3H)-thione (3). A series of novel 6-phenyl-thieno[3,2
d]pyrimidine derivatives 4-9 bearing different functional groups were synthesized
via treatment of compound 3 with different reagents. On the other hand, compound
2 was used to synthesize ethyl-[(3-methyl-6-phenyl-2-thioxo-2,3-dihydrothieno[
3,2-d]pyrimidin-4-yl)-oxy]acetate (10), 2-hydrazinyl- -3-methyl-6-phenyl
thieno[3,2-d]pyrimidin-4(3H)-one (11), 3-methyl-2-(methyl-sulfanyl)-6-phenyl
thieno[3,2-d]pyrimidin- 4(3H)-one (12) and N-(phenyl)/4-chlorophenyl or methoxy-
phenyl)-2-[(3-methyl-4-oxo-6-phenyl-3,4-dihydrothieno[ 3,2-d]pyrimidin-2-yl)
sulfanyl]-acetamide (13a-c). In addition, compound 12 was used to synthesize
thieno[1,2,4] triazolopyrimidine derivatives 14 and 15 and 3-methyl-2-(methyl
sulfonyl)-6-phenyl-thieno[3,2-d]pyrimidin-4(3H)-one (16) through the reaction
with the respective reagents. Moreover, the reaction of 16 with 4
phenylenediamine gave 2-[(4-aminophenyl)-amino]-3-methyl-6-phenyl-thieno[3,2-d]
pyrimidin-4(3H)-one (17), which reacted with methanesulfonyl chloride to afford N
{4-[(3-methyl-4-oxo-6-phenyl-3H,4H- -thieno[3,2-d]pyrimidin-2-yl)-amino]phenyl}
methanesulfonamide (18). The majority of the newly synthesized compounds
displayed potent anticancer activity, comparable to that of doxorubicin, on three
human cancer cell lines, including the human breast adenocarcinoma cell line (MCF
7), cervical carcinoma cell line (HeLa) and colonic carcinoma cell line (HCT-
116). Compounds 18, 13b and 10 were nearly as active as doxorubicin whereas
compounds 6, 7b and 15 exhibited marked growth inhibition, but still lower than
doxorubicin.
PMID- 29337677
TI - Synthesis and cytotoxicity evaluation of thiazole derivatives obtained from 2
amino-4,5,6,7-tetrahydrobenzo[b]thiophene- 3-carbonitrile.
AB - Reactivity of 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3- carbonitrile towards
thioglycolic acid resulted in thiazole derivative 1. The latter reacted with
different chemical reagents to give thiazole, pyrano[2,3-d]thiazole and thiazolo[
4,5-d]thiazole derivatives. Cytotoxicity effects of the newly synthesized
products against six cancer cell lines, namely, human gastric cancer (NUGC),
human colon cancer (DLD- 1), human liver cancer (HA22T and HEPG-2), human breast
cancer (MCF) and nasopharyngeal carcinoma (HONE-1) as well as against a normal
fibroblast cell (WI-38) were evaluated. The study showed that the 4,5,6,7
tetrahydrobenzo[ b] thiophene derivatives 6a, 7, 8a,b, 9b and 10b,c w ere t he
most active compounds. Their potencies were attributed to the presence of the
electron withdrawing groups.
PMID- 29337676
TI - Alkyl polyglucoside vs. ethoxylated surfactant-based microemulsions as vehicles
for two poorly water-soluble drugs: physicochemical characterization and in vivo
skin performance.
AB - Two types of biocompatible surfactants were evaluated for their capability to
formulate skin-friendly/non-irritant microemulsions as vehicles for two poorly
water-soluble model drugs differing in properties and concentrations: alkyl
polyglucosides (decyl glucoside and caprylyl/capryl glucoside) and ethoxylated
surfactants (glycereth-7-caprylate/ caprate and polysorbate 80). Phase behavior,
structural inversion and microemulsion solubilization potential for sertaconazole
nitrate and adapalene were found to be highly dependent on the surfactants
structure and HLB value. Performed characterization (polarized light microscopy,
pH, electrical conductivity, rheological, FTIR and DSC measurements) indicated a
formulation containing glycereth- 7-caprylate/caprate as suitable for
incorporation of both drugs, whereas alkyl polyglucoside-based systems did not
exhibit satisfying solubilization capacity for sertaconazole nitrate. Further,
monitored parameters were strongly affected by sertaconazole nitrate
incorporation, while they remained almost unchanged in adapalene-loaded vehicles.
In addition, results of the in vivo skin performance study supported acceptable
tolerability for all investigated formulations, suggesting selected
microemulsions as promising carriers worth exploring further for effective skin
delivery of model drugs.
PMID- 29337678
TI - Salivary sCD14 as a potential biomarker of dental caries activity in adults.
AB - CD14 is a co-receptor involved in the recognition of Gram-negative and Gram
positive bacteria, the latter known to cause dental caries. The aim of this study
was to determine whether soluble CD14 (sCD14) in saliva was associated with
caries activity and the collection method from the saliva. The study included 55
participants aged 20 to 40 years, 30 with dental caries and 25 caries-free
controls. We collected 110 saliva samples in total, 55 of resting saliva and 55
of mechanically stimulated saliva. Median levels of sCD14, measured with a matrix
matched enzyme-linked immunosorbent assay (ELISA), were higher in the caries
active than in the caries-free group in either resting (203.3 vs.167.9 ng mL-1;
P<0.01) or stimulated saliva (201 vs.105.7 ng mL-1; P<0.01). The resting salivary
flow rate was lower in the caries-active than caries-free group (0.61+/-0.42 vs.
0.98+/-0.52 mL min-1; P<0.01). Hyposalivation was observed only in the caries
active group (10 and 13 % in stimulated and resting saliva, respectively). Higher
salivary sCD14 levels and secretion rates were clearly associated with dental
caries and resting saliva. Future studies should focus on the clinical utility of
salivary sCD14 as a potential biomarker and predictor of future caries events.
PMID- 29337679
TI - The effects of physical activity on chronic subclinical systemic inflammation.
AB - Chronic subclinical systemic inflammation (CSSI) is a pathogenic event and a
common risk factor for many noncommunicable diseases like atherosclerosis,
metabolic syndrome, cardiovascular disease, insulin resistance and type 2
diabetes, cancer, and obstructive lung disease. On the other hand, regular
physical activity has been found to reduce this risk. Many studies of different
design were conducted to assess the association between inflammatory mediators as
markers of CSSI and regular physical activity. The aim of this review was to
present the current level of evidence and understanding of potential mechanisms
by which physical activity reduces inflammatory mediators involved in CSSI and
the types of physical activity required for the expected effect. We have found
that observational studies consistently report a positive association between
regular physical activity and lower CSSI, but the design of these studies does
not allow to infer a causal relationship. Interventional studies, in contrast,
were not consistent about the causal relationship between regular physical
activity and lower CSSI. The problem in interpreting these results lies in
significant differences between these interventional studies in their design,
sample size, study population, and intervention itself (intensity and extent,
follow up, weight loss). We can conclude that the scientific community has to
invest a significant effort into high-quality interventional trials focused on
finding the type, intensity, and extent of physical activity that would produce
the most favourable effect on CSSI.
PMID- 29337680
TI - In vitro assessment of the cytotoxic, DNA damaging, and cytogenetic effects of
hydroquinone in human peripheral blood lymphocytes.
AB - This study investigated the mechanisms of hydroquinone toxicity and assessed the
relationships between its cytotoxic, genotoxic, and cytogenetic effects tested at
8, 140, and 280 MUg mL-1 in human peripheral blood lymphocytes exposed for 24 h.
The outcomes of the treatments were evaluated using the apoptosis/necrosis assay,
the alkaline comet assay, and the cytokinesis-block micronucleus (CBMN) cytome
assay. The tested hydroquinone concentrations produced relatively weak
cytotoxicity in resting lymphocytes, which mostly died via apoptosis.
Hydroquinone's marked genotoxic effects were detected using the alkaline comet
assay. Significantly decreased values of all comet parameters compared to
controls indicated specific mechanisms of hydroquinone-DNA interactions. Our
results suggest that the two higher hydroquinone concentrations possibly led to
cross-linking and adduct formation. Increased levels of DNA breakage measured
following exposure to the lowest concentration suggested mechanisms related to
oxidative stress and inhibition of topoisomerase II. At 8 MUg mL-1, hydroquinone
did not significantly affect MN formation. At 140 and 280 MUg mL-1, it completely
blocked lymphocyte division. The two latter concentrations also led to
erythrocyte stabilization and prevented their lysis. At least two facts
contribute to this study's relevance: (I) this is the first study that quantifies
the degree of reduction in total comet area measured in lymphocyte DNA after
hydroquinone treatment, (II) it is also the first one on a lymphocyte model that
adopted the "cytome" protocol in an MN assay and found that lymphocytes exposure
even to low hydroquinone concentration resulted in a significant increase of
nuclear bud frequency. Considering the limitations of the lymphocyte model, which
does not possess intrinsic metabolic activation, in order to unequivocally prove
the obtained results further studies using other appropriate cell lines are
advised.
PMID- 29337681
TI - Dissipation dynamics of terbuthylazine in soil during the maize growing season.
AB - Ever since terbuthylazine (TBA) replaced atrazine in herbicide crop treatment,
its much greater persistence has raised considerable environmental concern. The
aim of our field experiment was to establish the dissipation dynamics of TBA and
its degradation product desethylterbuthylazine (DET) in soil over five months of
maize growth. We applied TBA as part of pre-emergent treatment in the regular and
double-the-regular amounts. Soil samples were collected periodically at the
following depths: 0-10 cm, 10-20 cm, 20-30 cm, and 30-50 cm. For TBA and DET soil
residue analysis we used microwave-assisted extraction with methanol, followed by
HPLC-UV/DAD. Regardless of the application rate, more than 80 % of the applied
TBA dissipated from the first 50 cm of soil in the two months after herbicide
application and 120 mm of rainfall. Three months later (at maize harvest), less
than 4 % of total TBA remained in the soil, mostly in the top 20 cm rich with
organic carbon on which TBA is likelier to adsorb. The loss of TBA from soil
coincided with the rise in DET, especially the top soil layers, during the
periods of low rainfall and highest soil temperatures. This points to
biodegradation as the main route of TBA dissipation in humic soils. The applied
amount had no significant effect on TBA dissipation in the top (humic) layers,
but in the layers with less than 1 % of organic carbon, it was higher when the
doublethe- regular dose was applied.
PMID- 29337682
TI - Adverse effects of organophosphorus pesticides on the liver: a brief summary of
four decades of research.
AB - Organophosphorus pesticides (OPs) are widely used volatile pesticides that have
harmful effects on the liver in acute and chronic exposures. This review article
summarises and discusses a wide collection of studies published over the last 40
years reporting on the effects of OPs on the liver, in an attempt to propose
general mechanisms of OP hepatotoxicity and possible treatment. Several key
biological processes have been reported as involved in OP-induced hepatotoxicity
such as disturbances in the antioxidant defence system, oxidative stress,
apoptosis, and mitochondrial and microsomal metabolism. Most studies show that
antioxidants can attenuate oxidative stress and the consequent changes in liver
function. However, few studies have examined the relationship between OP
structures and the severity and mechanism of their action. We hope that future in
vitro, in vivo, and clinical trials will answer the remaining questions about the
mechanisms of OP hepatotoxicity and its management.
PMID- 29337683
TI - How protein coronas determine the fate of engineered nanoparticles in biological
environment.
AB - Nanomedicine is a booming medical field that utilises nanoparticles (NPs) for the
development of medicines, medical devices, and diagnostic tools. The behaviour of
NPs in vivo may be quite complex due to their interactions with biological
molecules. These interactions in biological fluids result in NPs being enveloped
by dynamic protein coronas, which serve as an interface between NPs and their
environment (blood, cell, tissue). How will the corona interact with this
environment will depend on the biological, chemical, and physical properties of
NPs, the properties of the proteins that make the corona, as well as the
biological environment. This review summarises the main characteristics of
protein corona and describes its dynamic nature. It also presents the most common
analytical methods to study the corona, including examples of protein corona
composition for the most common NPs used in biomedicine. This knowledge is
necessary to design NPs that will create a corona with a desired efficiency and
safety in clinical use.
PMID- 29337684
TI - Hepatotoxicity associated with statins.
AB - Treatment with statins is known all over the world. They are generally considered
safe at therapeutic doses. Nevertheless, clinical trials are not enough to assess
their scarce adverse effects such as idiosyncratic drug induced liver injury
(DILI). Due to some conditions, such as concomitant usage (drug-drug interaction
using an identical metabolising enzyme) and genetic polymorphisms, there is an
increasing concern about their safety. Hepatotoxicity and rhabdomyolysis have
begun to appear in published studies. Most of investigations have focused on both
these adverse effects and mechanisms of drug induced toxicity. The present review
has attempted to compile almost all of the existing studies on the hepatotoxicity
of statins but not rhabdomyolysis. The aim of our study is to provide an overview
of the studies on the statin-associated hepatotoxicity and to discuss the
published studies. The researchers are of the opinion that the research on this
topic is incomplete but extremely necessary.
PMID- 29337685
TI - Radiological risk assessment: an overview of the ERICA Integrated Approach and
the ERICA Tool use.
AB - The ERICA project (Environmental Risk from Ionising Contaminants: Assessment and
Management) was co-funded by the European Union as part of the 6th Framework
Programme (FP EURATOM). The project was carried out between 2004 and 2007 as the
collective work of 15 organisations in seven European countries. Two significant
outputs of the project are the ERICA Integrated Approach and the ERICA Tool. The
ERICA Integrated Approach consists of three elements: assessment, risk
characterisation and management. The ERICA Tool is a practical implementation of
the assessment component of the ERICA Integrated Approach and has a three-tier
structure. The aim of this review paper is to give a concise overview of ERICA
project outputs and their structure, updates done since their first release in
2007, as well as to provide a context for their practical application in
environmental radiation protection and radiological risk assessments for various
engineering scenarios.
PMID- 29337686
TI - Forgotten public health impacts of cancer - an overview.
AB - Cancer is one of the diseases of greatest concern in developed countries and much
effort has been invested in discovering and developing therapeutics for curing
cancer. Despite the improvements in antineoplastic therapeutics in the last
decades, cancer is still one of the most harmful diseases worldwide. The global
burden of cancer also implies financial costs: these can be direct costs, such as
those related to treatment, care, and rehabilitation and indirect, which include
the loss of economic output due to missed work (morbidity costs) and premature
death (mortality costs). There are also hidden costs such as health insurance
premiums and nonmedical expenses that are worth noting. This paper intends to
present an overview of the generally forgotten impacts that the increasing number
of cancer cases can have on the environment, workers who handle antineoplastic
drugs, and health services. The knowledge available of each of the impacts will
be addressed and discussed regarding the expected development. Overall, lessons
learnt reflect on the impact of cancer through aspects not commonly evidenced in
the literature or even considered in socio-economic analysis, in part due to the
fact that these are difficult to contemplate in direct and indirect cancer costs
already defined. Attention may be drawn to the need of continuous investment in
prevention to reduce the negative impact on the environment, and in the health of
workers who handle antineoplastic drugs for patients' treatment.
PMID- 29337687
TI - Comparison of the solid phase and liquid-liquid extraction methods for methadone
determination in human serum and whole blood samples using gas
chromatography/mass spectrometry.
AB - The aim of this study was to determine the optimal biological sample and the
optimal extraction technique for monitoring methadone concentrations in
biological samples. We analysed methadone in serum and whole blood samples using
gas chromatography/mass spectrometry (GC/MS). Before analysis, we compared five
solid-phase extraction (SPE) and two liquid-liquid extraction (LLE) methods and
determined that SPE with Supelco LC-18 in serum yielded the best extraction
efficiency. The limit of detection was 10 ng mL-1 and the limit of quantification
25 ng mL-1. Correlation coefficient was over 0.999 for the methadone calibration
curve in linear range from 50 to 2000 ng mL-1. Intra and inter-day accuracy and
precision of the method was satisfactory. The method was successfully applied for
determining serum methadone in patients on maintenance therapy.
PMID- 29337688
TI - Interaction of the middle domains stabilizes Hsp90alpha dimer in a closed
conformation with high affinity for p23.
AB - The human genome encodes two highly similar cytosolic Hsp90 proteins called
isoforms Hsp90alpha and Hsp90beta. Of the 300 client proteins for Hsp90
identified so far only a handful interact specifically with one Hsp90 isoform.
Here we report for the first time that Hsp90 cochaperone p23 binds preferentially
to Hsp90alpha and that this interaction is mediated by the middle domain of
Hsp90alpha. Based on the homology modeling, we infer that the middle domains in
the Hsp90alpha dimer bind stronger with each other than in the Hsp90beta dimer.
Therefore, compared to Hsp90beta, Hsp90alpha may adopt closed conformation more
easily. Hsp90 interacts with p23 in the closed conformation. Hsp90alpha binds
human recombinant p23 about three times stronger than Hsp90beta but with
significantly smaller exothermic enthalpy as determined by isothermal titration
calorimetry of direct binding between the purified proteins. As p23 binds to
Hsp90 in a closed conformation, stabilization of the Hsp90alpha dimer in the
closed conformation by its middle domains explains preference of p23 to this
Hsp90 isoform.
PMID- 29337689
TI - Abeta42 oligomers impair the bioenergetic activity in hippocampal synaptosomes
derived from APP-KO mice.
AB - Employing hippocampal synaptosomes from amyloid precursor protein (APP)-deleted
mice we analyzed the immediate effects of amyloid beta peptide 42 (Abeta42)
peptide in its oligomeric or fibrillar assembly or of soluble amyloid precursor
protein alpha (sAPPalpha) protein on their bioenergetic activity. Upon
administration of oligomeric Abeta42 peptide for 30 min we observed a robust
decrease both in mitochondrial activity and in mitochondrial membrane potential
(MMP). In contrast the respective fibrillary or scrambled peptides showed no
effect, indicating that inhibition strictly depends on the oligomerization status
of the peptide. Hippocampal synaptosomes from old APP-KO mice revealed a further
reduction of their already impaired bioenergetic activity upon incubation with 10
MUm Abeta42 peptide. In addition we evaluated the influence of the sAPPalpha
protein on mitochondrial activity of hippocampal synaptosomes derived from young
or old APP-KO animals. In neither case 20 nm nor 200 nm sAPPalpha protein had an
effect on mitochondrial metabolic activity. Our findings demonstrate that
hippocampal synaptosomes derived from APP-KO mice are a most suitable model
system to evaluate the impact of Abeta42 peptide on its bioenergetic activity and
to further elucidate the molecular mechanisms underlying the impairments by
oligomeric Abeta42 on mitochondrial function. Our data demonstrate that
extracellular Abeta42 peptide is taken up into synaptosomes where it immediately
attenuates mitochondrial activity.
PMID- 29337690
TI - Molecular determinants of Drosophila immunophilin FKBP39 nuclear localization.
AB - FK506-binding proteins (FKBPs) belong to a distinct class of immunophilins that
interact with immunosuppressants. They use their peptidyl-prolyl isomerase
(PPIase) activity to catalyze the cis-trans conversion of prolyl bonds in
proteins during protein-folding events. FKBPs also act as a unique group of
chaperones. The Drosophila melanogaster peptidyl-prolyl cis-trans isomerase FK506
binding protein of 39 kDa (FKBP39) is thought to act as a transcriptional
modulator of gene expression in 20-hydroxyecdysone and juvenile hormone signal
transduction. The aim of this study was to analyze the molecular determinants
responsible for the subcellular distribution of an FKBP39-yellow fluorescent
protein (YFP) fusion construct (YFP-FKBP39). We found that YFP-FKBP39 was
predominantly nucleolar. To identify the nuclear localization signal (NLS), a
series of YFP-tagged FKBP39 deletion mutants were prepared and examined in vivo.
The identified NLS signal is located in a basic domain. Detailed mutagenesis
studies revealed that residues K188 and K191 are crucial for the nuclear
targeting of FKBP39 and its nucleoplasmin-like (NPL) domain contains the sequence
that controls the nucleolar-specific translocation of the protein. These results
show that FKBP39 possesses a specific NLS in close proximity to a putative helix
turn-helix (HTH) motif and FKBP39 may bind DNA in vivo and in vitro.
PMID- 29337691
TI - The neutral sphingomyelinase 2 in T cell receptor signaling and polarity.
AB - By hydrolyzing its substrate sphingomyelin at the cytosolic leaflet of cellular
membranes, the neutral sphingomyelinase 2 (NSM2) generates microdomains which
serve as docking sites for signaling proteins and thereby, functions to regulate
signal relay. This has been particularly studied in cellular stress responses
while the regulatory role of this enzyme in the immune cell compartment has only
recently emerged. In T cells, phenotypic polarization by co-ordinated
cytoskeletal remodeling is central to motility and interaction with endothelial
or antigen-presenting cells during tissue recruitment or immune synapse
formation, respectively. This review highlights studies adressing the role of
NSM2 in T cell polarity in which the enzyme plays a major role in regulating
cytoskeletal dynamics.
PMID- 29337692
TI - Generation of superoxide and hydrogen peroxide by side reactions of mitochondrial
2-oxoacid dehydrogenase complexes in isolation and in cells.
AB - Mitochondrial 2-oxoacid dehydrogenase complexes oxidize 2-oxoglutarate, pyruvate,
branched-chain 2-oxoacids and 2-oxoadipate to the corresponding acyl-CoAs and
reduce NAD+ to NADH. The isolated enzyme complexes generate superoxide anion
radical or hydrogen peroxide in defined reactions by leaking electrons to oxygen.
Studies using isolated mitochondria in media mimicking cytosol suggest that the 2
oxoacid dehydrogenase complexes contribute little to the production of superoxide
or hydrogen peroxide relative to other mitochondrial sites at physiological
steady states. However, the contributions may increase under pathological
conditions, in accordance with the high maximum capacities of superoxide or
hydrogen peroxide-generating reactions of the complexes, established in isolated
mitochondria. We assess available data on the use of modulations of enzyme
activity to infer superoxide or hydrogen peroxide production from particular 2
oxoacid dehydrogenase complexes in cells, and limitations of such methods to
discriminate specific superoxide or hydrogen peroxide sources in vivo.
PMID- 29337693
TI - In vitro reconstitution and biochemical characterization of human phospholipid
scramblase 3: phospholipid specificity and metal ion binding studies.
AB - Human phospholipid scramblase 3 (hPLSCR3) is a single pass transmembrane protein
that plays a vital role in fat metabolism, mitochondrial function, structure,
maintenance and apoptosis. The mechanism of action of scramblases remains still
unknown, and the role of scramblases in phospholipid translocation is heavily
debated. hPLSCR3 is the only member of scramblase family localized to
mitochondria and is involved in cardiolipin translocation at the mitochondrial
membrane. Direct biochemical evidence of phospholipid translocation by hPLSCR3 is
yet to be reported. Functional assay in synthetic proteoliposomes upon Ca2+ and
Mg2+ revealed that, apart from cardiolipin, recombinant hPLSCR3 translocates
aminophospholipids such as NBD-PE and NBD-PS but not neutral phospholipids. Point
mutation in hPLSCR3 (F258V) resulted in decreased Ca2+ binding affinity.
Functional assay with F258V-hPLSCR3 led to ~50% loss in scramblase activity in
the presence of Ca2+ and Mg2+. Metal ion-induced conformational changes were
monitored by intrinsic tryptophan fluorescence, circular dichroism, surface
hydrophobicity changes and aggregation studies. Our results revealed that Ca2+
and Mg2+ bind to hPLSCR3 and trigger conformational changes mediated by
aggregation. In summary, we suggest that the metal ion-induced conformational
change and the aggregation of the protein are essential for the phospholipid
translocation by hPLSCR3.
PMID- 29337694
TI - Magnetic and structural depth profiles of Heusler alloy Co2FeAl0.5Si0.5 epitaxial
films on Si(1 1 1).
AB - The depth-resolved chemical structure and magnetic moment of [Formula: see text],
thin films grown on Si(1 1 1) have been determined using x-ray and polarized
neutron reflectometry. Bulk-like magnetization is retained across the majority of
the film, but reduced moments are observed within 45[Formula: see text] of the
surface and in a 25[Formula: see text] substrate-interface region. The reduced
moment is related to compositional changes due to oxidation and diffusion, which
are further quantified by elemental profiling using electron microscopy with
electron energy loss spectroscopy. The accuracy of structural and magnetic depth
profiles obtained from simultaneous modeling is discussed using different
approaches with different degree of constraints on the parameters. Our approach
illustrates the challenges in fitting reflectometry data from these multi
component quaternary Heusler alloy thin films.
PMID- 29337696
TI - High-pressure structural and vibrational properties of monazite-type BiPO4,
LaPO4, CePO4, and PrPO4.
AB - Monazite-type BiPO4, LaPO4, CePO4, and PrPO4 have been studied under high
pressure by ab initio simulations and Raman spectroscopy measurements in the
pressure range of stability of the monazite structure. A good agreement between
experimental and theoretical Raman-active mode frequencies and pressure
coefficients has been found which has allowed us to discuss the nature of the
Raman-active modes. Besides, calculations have provided us with information on
how the crystal structure is modified by pressure. This information has allowed
us to determine the equation of state and the isothermal compressibility tensor
of the four studied compounds. In addition, the information obtained on the
polyhedral compressibility has been used to explain the anisotropic axial
compressibility and the bulk compressibility of monazite phosphates. Finally, we
have carried out a systematic discussion on the high-pressure behavior of the
four studied phosphates in comparison to results of previous studies.
PMID- 29337697
TI - Enhanced second harmonic generation from a plasmonic Fano structure subjected to
an azimuthally polarized light beam.
AB - We show that an azimuthally polarized beam (APB) excitation of a plasmonic Fano
structure made by coupling a split-ring resonator (SRR) to a nanoarc can enhance
second harmonic generation (SHG). Strikingly, an almost 30 times enhancement in
SHG peak intensity can be achieved when the excitation is switched from a
linearly polarized beam (LPB) to an APB. We attribute this significant
enhancement of SHG to the corresponding increase in the local field intensity at
the fundamental frequency of SHG, resulting from the improved conversion
efficiency between the APB excitation and the plasmonic modes of the Fano
structure. We also show that unlike LPB, APB excitation creates a symmetric SHG
radiation pattern. This effect can be understood by considering an interference
model in which the APB can change the total SHG far-field radiation by modifying
the amplitudes and phases of two waves originating from the individual SRR and
nanoarc of the Fano structure.
PMID- 29337695
TI - Automated fabrication of photopatterned gelatin hydrogels for organ-on-chips
applications.
AB - Organ-on-chip platforms aim to improve preclinical models for organ-level
responses to novel drug compounds. Heart-on-a-chip assays in particular require
tissue engineering techniques that rely on labor-intensive photolithographic
fabrication or resolution-limited 3D printing of micropatterned substrates, which
limits turnover and flexibility of prototyping. We present a rapid and automated
method for large scale on-demand micropatterning of gelatin hydrogels for organ
on-chip applications using a novel biocompatible laser-etching approach. Fast and
automated micropatterning is achieved via photosensitization of gelatin using
riboflavin-5'phosphate followed by UV laser-mediated photoablation of the gel
surface in user-defined patterns only limited by the resolution of the 15 MUm
wide laser focal point. Using this photopatterning approach, we generated
microscale surface groove and pillar structures with feature dimensions on the
order of 10-30 MUm. The standard deviation of feature height was 0.3 MUm,
demonstrating robustness and reproducibility. Importantly, the UV-patterning
process is non-destructive and does not alter gelatin micromechanical properties.
Furthermore, as a quality control step, UV-patterned heart chip substrates were
seeded with rat or human cardiac myocytes, and we verified that the resulting
cardiac tissues achieved structural organization, contractile function, and long
term viability comparable to manually patterned gelatin substrates. Start-to
finish, UV-patterning shortened the time required to design and manufacture
micropatterned gelatin substrates for heart-on-chip applications by up to 60%
compared to traditional lithography-based approaches, providing an important
technological advance enroute to automated and continuous manufacturing of organ
on-chips.
PMID- 29337698
TI - Fe and Co NMR studies of magnetoelectric Co2 Y-type hexaferrite BSCFAO.
AB - The Fe3+ and Co2+ NMR spectra for Ba0.3Sr1.7Co2(Fe0.96Al0.04)12O22 (BSCFAO) and
Ba0.3Sr1.7Co2Fe12O22 (BSCFO) were obtained in a zero magnetic field at a low
temperature. We observed change in the enhancement effect of the NMR signals
depending on the setting field, which was varied when applied along the b-axis
and then turned off before the measurement was taken. The experimental results
indicate that the magnetic structure changes from an alternating longitudinal
cone to a transverse cone when the setting field is 250 mT. They also show that
the spins of Co2+ ions together with those of Fe3+ ions constitute a part of the
overall magnetic structure and that the substitution of Al3+ for Fe3+ weakens the
magnetic anisotropy within the easy plane. From a comparison of the enhancement
factors of the Fe3+ NMR obtained with the RF pulse applied along the a-axis and
the c-axis, we found that the magnetic easy plane anisotropy is approximately 16
times greater than the anisotropy within the easy plane. No changes of the NMR
spectra were observed under an electric field of 1.2 MV m-1.
PMID- 29337700
TI - Increased resistance to tissue plasminogen activator-induced fibrinolysis in
healthy subjects from Thailand.
AB - : There is significant variability in blood coagulation among world populations.
In particular, there may exist important differences in regulation of the
fibrinolytic system in Asian populations that contribute to diseases of
thrombosis and hemostasis. To investigate this issue, we compared fibrinogen
concentration, plasma clot formation, and fibrinolytic resistance of healthy
Asian subjects from Hat Yai, Songkhla, Thailand (Thai) vs. healthy North American
subjects from Seattle, Washington, USA (SEA). Citrated plasma samples were
obtained from healthy adult volunteers. Fibrinogen concentration was measured in
plasma by the method of Clauss to examine for baseline differences of fibrinogen
concentration. Samples were then standardized to 2.8 mg/ml fibrinogen using
physiological buffer for each sample prior to fibrinolytic testing using
rotational thromboelastometry (ROTEM) to examine for differences of clot lysis
not attributable to fibrinogen concentration alone. Clot lysis was examined with
ROTEM extrinsic pathway activation in the presence of 0, 0.5, and 1.0 MUg/ml of
tissue plasminogen activator (tPA). Two-way repeated measures analysis of
variance was used to determine the effects of tPA and study group on ROTEM
parameters. N = 49 Thai samples were compared with N = 58 SEA samples. Mean (SD)
fibrinogen concentration was significantly increased for the Thai group at 4.03
(0.79) mg/ml vs. the SEA group at 3.66 (0.70) mg/ml (t test P = 0.014). After
standardization of all samples to equivalent fibrinogen concentration, there were
no differences in clot formation between groups without tPA. There was a
significant effect of increasing tPA concentration on all ROTEM parameters except
for clotting time. There were significant individual differences for amplitude at
10 min and lysis onset time, where amplitude at 10 min was significantly
increased and lysis onset time was significantly prolonged for Thai vs. SEA at
tPA concentrations of 0.5 and 1.0 MUg/ml. Variability in thrombosis and
hemostasis in Asians vs. other populations is likely to involve differences of
fibrinogen concentration and regulation of clot lysis.
PMID- 29337701
TI - Update on metal-induced occupational lung disease.
AB - PURPOSE OF REVIEW: Occupational and environmental exposures to metals can result
in multiple pulmonary conditions. This article will review recent epidemiologic
and mechanistic studies that have enhanced our understanding of the association
between particular lung diseases and exposure to specific metals. RECENT
FINDINGS: Recent studies have broadened our understanding of the mechanisms of
lung diseases such as CBD in established industries and drawn attention to
conditions that may arise from exposure to metals such as indium in developing
technologies. New diagnostic techniques such as elemental tissue analysis may
help establish a diagnosis of metal-induced occupational lung disease. Electronic
cigarette devices, environmental pollutants, and the growing use of nanoparticle
sized metals pose additional risks to workers and consumers. SUMMARY: Recognizing
the risks of pulmonary disease in workers exposed to metals and performing a
thorough occupational history and diagnostic work-up in patients with unexplained
respiratory findings is necessary to promote understanding and prevention of
metal-induced lung disease.
PMID- 29337699
TI - Associations Between Nurse-Guided Variables and Plasma Oxytocin Trajectories in
Premature Infants During Initial Hospitalization.
AB - BACKGROUND: Oxytocin (OT) is a social hormone that may help researchers
understand how nurse-guided interventions during initial infant hospitalization,
such as supporting human milk expression, promoting comforting touch, and
reducing exposure to stressors, affect preterm brain development. PURPOSE: To
determine whether factors related to human milk, touch, or stressor exposure are
related to plasma OT trajectories in premature infants. METHODS: Plasma from 33
premature infants, born gestational ages 25 to (Equation is included in full-text
article.)weeks, was collected at 14 days of life and then weekly until 34 weeks'
corrected gestational age (CGA). Variables related to feeding volumes of human
milk and formula; touch, as indexed by skin-to-skin contact (SSC) and swaddled
holding; and clinical stressors were extracted from the electronic medical
record. Linear mixed-models tested associations between nurse-guided variables
and plasma OT trajectories. RESULTS: In the final model, same-day SSC was
positively related not only to plasma OT levels at 27 weeks' CGA (beta= .938, P =
.002) but also to a decline in plasma OT levels over time (beta=-.177, P = .001).
Volume of enteral feeds (mL/kg/d), its interaction with CGA, and number of
stressful procedures were not statistically significant (beta= .011, P = .077;
beta=-.002, P = .066; and beta= .007, P = .062, respectively). IMPLICATIONS FOR
PRACTICE: Nurse-guided interventions are associated with infant plasma OT levels,
suggesting nurses may impact the neurobiology of the developing premature infant.
IMPLICATIONS FOR RESEARCH: Replication with larger sample sizes and randomized
controlled trial designs is needed to test effects of specific nursing
interventions on infant OT.
PMID- 29337702
TI - Changing concepts of HIV infection and renal disease.
AB - PURPOSE OF REVIEW: Human immunodeficiency virus (HIV)-associated nephropathy
(HIVAN) was identified as the major renal manifestation of HIV infection early in
the HIV epidemic. However, HIV infection now is associated with a different
spectrum of renal lesions leading to chronic kidney disease. This review examines
the changes in kidney injury occurring in the current HIV era and the factors
involved in this transformation of disease expression. RECENT FINDINGS: The
incidence of HIVAN and opportunistic infections in HIV-infected individuals has
declined in concert with the use of effective combination antiretroviral agents.
Chronic kidney disease has become more prevalent as patients infected with HIV
are living longer and developing non-HIV-associated diseases such as hypertension
and diabetes. Additionally, noncollapsing focal and segmental glomerulosclerosis,
co-infection with hepatitis C, HIV-associated immune complex kidney disease, HIV
related accelerated aging, and antiretroviral therapies contribute to progressive
loss of renal function. SUMMARY: HIV infection is now associated with a variety
of renal lesions causing chronic kidney disease, not all of which are virally
induced. It is important to determine the cause of renal functional decline in an
HIV-infected patient, as this will impact patient management and prognosis.
PMID- 29337703
TI - New antibiotics for ventilator-associated pneumonia.
AB - PURPOSE OF REVIEW: Ventilator-associated pneumonia (VAP) caused by multidrug
resistant (MDR) bacteria represents a global emerging problem. Delayed
prescription of an adequate treatment for VAP has been associated with higher
morbidity and mortality. New molecules have been developed to face the need of
compounds that are active against resistant Gram-positive and Gram-negative
pathogens. The aim of this review is to summarize the current scenario of new
therapeutic options for the treatment of VAP. RECENT FINDINGS: A number of new
antibiotics with activity against MDR have been recently approved for the
treatment of VAP, and other agents are under investigation. In this review, the
authors summarize the current therapeutic options for the treatment of VAP that
showed promising implications for clinical practice, including new compounds
belonging to old antibiotic classes (e.g., ceftolozane/tazobactam,
ceftazidime/avibactam meropenem/vaborbactam, imipenem/relebactam, tedizolid,
cefiderocol, eravacycline, and plazomicin) and novel chemical classes, such as
murepavadin. Nebulized antibiotics that are currently in development for the
treatment of pneumonia in mechanically ventilated patients are also presented.
SUMMARY: Newly approved and investigational drugs for the treatment of VAP are
expected to offer many advantages for the management of patients with respiratory
infections caused by MDR. Promising characteristics of new compounds include high
activity against both methicillin-resistant Staphylococcus aureus and MDR Gram
negative bacteria and a favorable safety profile.
PMID- 29337704
TI - The what, when and how in performing and interpreting microbiological diagnostic
tests in skin and soft tissue infections.
AB - PURPOSE OF REVIEW: To summarize and classify the most recent and relevant
microbiological studies for each type of skin and soft tissue infection (SSTI).
RECENT FINDINGS: Following Infectious Diseases Society of America and Food and
Drug Administration classifications of SSTIs, we differentiate between two large
groups, the superficial or uncomplicated infections and the complicated
infections with deep involvement. It is not usually necessary to obtain
microbiological samples in uncomplicated infections, except in cases of
recurrences or for epidemiological control purposes. In the case of complicated
infections, the samples are of two different types: those obtained from the
affected area (surgical samples, punctures of abscesses or swabs) and systemic
samples (i.e. blood cultures). The clinical condition also determines the type of
samples to be obtained. In cases of systemic involvement, blood cultures are
mandatory. For immunocompromised patients, who may present atypical infections,
detection of antigens, serologies or molecular biology techniques may be helpful.
The rapid diagnosis is currently the goal to be pursued by implementing
techniques such as matrix assisted laser desorption ionization-time of flight,
commercial real-time PCR or the promising metagenomics. SUMMARY: Microbiological
diagnosis is one of the cornerstones of the management of SSTIs. Prompt obtaining
and processing of the necessary samples, depending on the clinical situation of
the patient, is of relevance in the decision-making process. Rapid and fluid
reporting of the results (identification, mechanisms of resistance and
antibiogram) will improve the management of these patients.
PMID- 29337705
TI - How does 'metabolic surgery' work its magic? New evidence for gut microbiota.
AB - PURPOSE OF REVIEW: Metabolic surgery is recommended for the treatment of type 2
diabetes for its potent ability to improve glycemic control. However, the
mechanisms underlying the beneficial effects of metabolic surgery are still under
investigation. We provide an updated review of recent studies into the molecular
underpinnings of metabolic surgery, focusing in on what is known about the role
of gut microbiota. Over the last 7 years several reports have been published on
the topic, however the field is expanding rapidly. RECENT FINDINGS: Studies have
now linked the regulation of glucose and lipid metabolism, neuronal and
intestinal adaptations, and hormonal and nutrient signaling pathways to gut
microbiota. Given that the composition of gut microbiota is altered by metabolic
surgery, investigating the potential mechanism and outcomes of this change are
now a priority to the field. SUMMARY: As evidence for a role for microbiota
builds, we expect future patients may receive microbe-based therapeutics to
improve surgical outcomes and perhaps one day preclude the need for surgical
therapies all together. In this review and perspective, we evaluate the current
state of the field and its future.
PMID- 29337706
TI - Cholesterol efflux in the transplant patient.
AB - PURPOSE OF REVIEW: Cholesterol metabolism is increasingly recognized in
inflammatory diseases including transplantation. This review discusses the
mechanistic underpinnings that tie macrophage cholesterol efflux capacity (CEC)
of high-density lipoprotein (HDL) to chronic rejection in transplanted patients.
RECENT FINDINGS: Animal studies suggest that administration of apolipoprotein A
I, the main protein constituent of HDL, can prevent transplant arteriosclerosis.
apoA-I administration increases CEC of HDL. In patients with cardiac allograft
vasculopathy (CAV), decreased CEC has been associated with poorer survival. In
addition, reduced CEC in recipients, pretransplant, has been associated with the
development of CAV and renal allograft survival. SUMMARY: These recent findings
raise the hypothesis that increasing cholesterol efflux may prevent chronic
rejection and improve allograft survival after transplant. Reconstituted HDL
significantly increases CEC and is currently in clinical development for
traditional atherosclerosis. Clinical trials of reconstituted HDL administration
in transplantation should be performed.
PMID- 29337707
TI - Induction chemotherapy in acute myeloid leukaemia: origins and emerging
directions.
AB - PURPOSE OF REVIEW: This review summarizes the hallmark developments in induction
chemotherapy for acute myeloid leukaemia and further describes future directions
in its evolution. RECENT FINDINGS: We describe the origin of induction
chemotherapy. We also describe notable modifications and adjustments to 7+3
induction chemotherapy since its development. Finally, we describe new efforts to
modify and add new agents to induction therapy, including '7+3 Plus'
combinations. SUMMARY: Induction chemotherapy remains the standard of care for
the majority of patients with acute myeloid leukaemia. However, its success is
limited in a subset of patients by toxicity, failure to achieve remission and
potential for subsequent relapse. Novel agents such as mutant fms like tyrosine
kinase 3 inhibitors, mutant isocitrate dehydrogenase inhibitors, CD33-antibody
drug conjugates and liposomal formulations have demonstrated significant
potential as modifications to traditional induction chemotherapy.
PMID- 29337708
TI - Using Iterative Plan-Do-Study-Act Cycles to Improve Teaching Pedagogy.
AB - Most students entering nursing programs today are members of Generation Y or the
Millennial generation, and they learn differently than previous generations.
Nurse educators must consider implementing innovative teaching strategies that
appeal to the newest generation of learners. The Plan-Do-Study-Act cycle is a
framework that can be helpful when planning, assessing, and continually improving
teaching pedagogy. This article describes the use of iterative Plan-Do-Study-Act
cycles to implement a change in teaching pedagogy.
PMID- 29337709
TI - The Relationship Between Socioeconomic Status (SES) and NCLEX-RN: Comparing SES
Indicators in Mediated Logistic Regression.
AB - The main purpose of this study was to examine the relationship between
socioeconomic status (SES), ACT test scores, and the National Council Licensure
Examination-Registered Nurse (NCLEX-RN) through a mediated logistic regression
model. ACT is often considered one of the strongest predictors of success on the
NCLEX-RN. Data from nursing students (N = 1,176) at a large, Midwestern
university were analyzed. The goal was to determine if the predictive power of
ACT on the NCLEX-RN stems from the influence of SES on ACT. A significant
indirect effect through the causal chain of Pell Grant eligibility (i.e., SES)
>ACT->NCLEX-RN was found.
PMID- 29337710
TI - Analysis of First-Time Unsuccessful Attempts on the Certified Nurse Educator
Examination.
AB - AIM: This retrospective analysis examined first-time unsuccessful attempts on the
Certified Nurse Educator (CNE) examination from September 2005 through September
2011 (n = 390). BACKGROUND: There are few studies examining certification within
the academic nurse educator role. There is also a lack of evidence to assist
nurse educators in understanding those factors that best support success on the
CNE exam. METHOD: Nonexperimental, descriptive, retrospective correlational
design using chi-square test of independence and factorial analyses of variance.
RESULTS: A statistically significant relationship was found between first-time
failure and highest degree obtained and institutional affiliation on the CNE
exam. There was no statistically significant effect on mean scores in any of the
six content areas measured by the CNE exam as related to highest degree or
institutional affiliation. CONCLUSION: The findings from this study support a
previous recommendation for faculty development, experience in the role, and
doctoral preparation prior to seeking certification.
PMID- 29337711
TI - Why We Became Nurse Educators: Findings From a Nationwide Survey of Current Nurse
Educators.
AB - AIM: The aim of the study was to identify what a national sample of nurse faculty
believe will help build the faculty population. BACKGROUND: The aging population
contributes to the need for new nurses while reducing the number of experienced
faculty. Retaining faculty and attracting younger faculty are essential. METHOD:
This descriptive study used an online survey. Nurse educators teaching at all
levels (n = 940) were asked to rate the effectiveness of attraction, recruitment,
and retention strategies. This article reports on responses to one of the
survey's open-ended question; a content analysis was conducted to develop a
narrative description about why respondents chose nursing education. RESULTS:
Respondents wanted to teach in a stimulating yet flexible work environment, hoped
to influence the profession, had been influenced by educators, and sought change
and challenge in their careers. CONCLUSION: Faculty find nursing academia
satisfying and rewarding, but noncompetitive compensation and unsatisfactory work
environments can eclipse satisfiers.
PMID- 29337712
TI - Femoral Component Sizing During Total Knee Arthroplasty: Anterior Versus
Posterior Referencing.
PMID- 29337713
TI - Calculated versus Measured MVV-Surrogate Marker of Ventilatory CPET-Erratum.
PMID- 29337714
TI - Greater Effect of East versus West Travel on Jet Lag, Sleep, and Team Sport
Performance-Erratum.
PMID- 29337715
TI - Labyrinthine Sequestrum: A Case Report and Review of the Literature.
AB - OBJECTIVE: To report the presentation, diagnosis, management, and convalescence
of labyrinthine sequestrum (LS) and summarize all previously published cases.
PATIENT(S): Eleven-year-old female with LS. INTERVENTION(S): Multidisciplinary
diagnostic evaluation and treatment. MAIN OUTCOME MEASURES: Imaging and
laboratory findings, medical and surgical treatment. RESULTS: We describe a case
of LS secondary to medically recalcitrant suppurative otitis media in an 11-year
old female and review all eight previously reported cases. The index patient
presented after 6 months of otitis media, profound unilateral hearing loss, with
symptoms suggesting meningitis. Temporal bone CT demonstrated marked bony
destruction of the left otic capsule. Gadolinium-enhanced MRI showed an enhancing
process with evidence of meningitis and subdural empyema. The patient was treated
with surgical debridement and culture directed antibiotic therapy. Posttreatment
imaging showed resolution of intracranial infection with fibrous bony healing of
the otic capsule resembling fibrous dysplasia. CONCLUSION: LS is a rare form of
labyrinthitis characterized by centrifugal destruction of the otic capsule. The
current index case highlights the importance of combined medical and surgical
treatment and describes for the first time in the literature the fibrous
ossification of the otic capsule following disease resolution.
PMID- 29337716
TI - Management of Biceps Tendon Pathology: From the Glenoid to the Radial Tuberosity.
AB - Management of proximal and distal biceps tendon pathology is evolving. The long
head of the biceps tendon, if inflamed, may be a pain-producing structure. In
appropriately indicated patients, a symptomatic long head of the biceps tendon
can be surgically managed via tenotomy, tenodesis, and/or superior labrum
anterior to posterior repair. In some patients, primary superior labrum anterior
to posterior pathology can be managed via biceps tenodesis. Determining which
procedure is most appropriate and which technique and implant are preferred for a
given patient with biceps tendon pathology is controversial. Less debate exists
with regard to the timing of distal biceps tendon repair; however, considerable
controversy exists with regard to selection of an appropriate surgical technique
and implant. In addition, the treatment of patients with a chronic and/or
retracted distal biceps tendon tear and patients in whom distal biceps tendon
repair fails is extremely challenging. Orthopaedic surgeons should understand the
anatomy of, nonsurgical and surgical treatment options for, and outcomes of
patients with proximal or distal biceps tendon pathology.
PMID- 29337717
TI - Transforaminal Lumbar Interbody Fusion: Traditional Open Versus Minimally
Invasive Techniques.
AB - Recently, minimally invasive spine arthrodesis has gained popularity among spine
surgeons. Minimally invasive techniques have advantages and disadvantages
compared with traditional open techniques. Comparisons between short-term
outcomes of minimally invasive transforaminal interbody fusion and open
transforaminal interbody fusion in terms of estimated blood loss, postoperative
pain, and hospital length of stay have been well documented and generally favor
the minimally invasive technique. However, the advantages of minimally invasive
transforaminal interbody fusion must be evaluated in the context of long-term
results, such as patient-reported outcomes and the success of arthrodesis.
Because the literature is equivocal in identifying the superior technique for
successful long-term outcomes, more study is needed. Patient safety, the risk of
complications, and the cost of these techniques also must be considered.
PMID- 29337718
TI - Physical Inactivity from Youth to Adulthood and Risk of Impaired Glucose
Metabolism.
AB - INTRODUCTION: Physical activity (PA) is important in the prevention and treatment
of impaired glucose metabolism. However, association of physical inactivity
during the transition between childhood and adulthood with glucose metabolism is
unknown. Therefore, we studied the association of persistent physical inactivity
since childhood with glucose metabolism in adulthood. METHODS: Data were drawn
from the ongoing, Cardiovascular Risk in Young Finns Study with repeated follow
ups between 1980 and 2011 (baseline age, 3-18 yr; n = 3596). Impaired glucose
metabolism was defined as having impaired fasting glucose (6.1-6.9 mmol.L) or
type 2 diabetes in adulthood. Leisure-time PA habits were repeatedly collected
with a standardized questionnaire and expressed as a PA Index. Using PA Index,
four groups were formed (n = 2000): 1) persistently low PA, 2) decreasingly
active, 3) increasingly active, and 4) persistently active subjects. Poisson
regression model was used to examine the association between PA groups and
impaired glucose metabolism. RESULTS: The proportion of the sample with impaired
glucose metabolism was 16.1% in individuals with persistently low PA, 14.5% in
decreasingly active, 6.8% in increasingly active, and 11.1% in persistently
active. Compared with individuals with persistently low PA, age and sex-adjusted
risk for impaired glucose metabolism were lower in those who increased PA
(relative risk [RR], 0.47; 95% confidence interval [CI], 0.29-0.76) and in those
who were persistently active (RR, 0.70; 95% CI, 0.51-0.97), but similar in those
who decreased PA (RR, 0.93; 95% CI, 0.66-1.36). CONCLUSIONS: Persistently
physically inactive lifestyle from youth to adulthood is associated with
increased risk of impaired glucose metabolism in adulthood. Importantly, a
moderate increase in PA lowered the risk. The results highlight the importance of
avoiding physically inactive lifestyle at all stages of life.
PMID- 29337719
TI - The effect of a hybrid training program.
AB - Improving nursing communication skills and HCAHPS scores.
PMID- 29337720
TI - Update on the Role of Actovegin in Musculoskeletal Medicine: A Review of the Past
10 Years.
AB - BACKGROUND: Actovegin is a biological drug with a controversial history of use in
the treatment of sports injuries during the past 60 years. Particular concerns
have been raised about its ergogenic potential to enhance performance, but some
of these have been based on little more than anecdote. OBJECTIVES: In this
article, we review the most recent scientific evidence to determine the clinical
efficacy, safety profile, and legal status of Actovegin. METHODS: We considered
all studies directly commenting on experience with Actovegin use as the primary
intervention within the past 10 years. Outcomes included mechanisms of action,
clinical efficacy in enhancing muscle repair, any report of safety issues, and
any evidence for ergogenic effect. RESULTS: Our database search returned 212
articles, abstracts were screened, and after inclusion/exclusion criteria were
applied, 25 articles were considered: Publications included 11 primary research
articles (7 in vitro studies and 4 clinical trials), 8 review articles, 5
editorials, and a single case report. CONCLUSIONS: Current literature is still
yet to define the active compound(s) of Actovegin, but suggests that it shows
antioxidant and antiapoptotic properties, and may also upregulate macrophage
responses central to muscle repair. Clinical efficacy was supported by one new
original research article, and the use of Actovegin to treat muscle injuries
remains safe and supported. Two articles argued the ergogenic effect of
Actovegin, but in vitro findings did not to translate to the outcomes of a
clinical trial. An adequate and meaningful scientific approach remains difficult
in a field where there is immense pressure to deliver cutting-edge therapies.
PMID- 29337722
TI - In Response to: Influence and Reliability of Different Correction Formulas on QTc
Calculation.
PMID- 29337721
TI - Continuing Play, Symptom Severity, and Symptom Duration After Concussion in Youth
Athletes.
AB - OBJECTIVE: To determine whether continuing to play after a concussion is
associated with higher symptom burden or prolonged symptom duration. DESIGN:
Patients who presented for care at a sport concussion clinic within the first 3
weeks of injury were asked whether they continued to play immediately after their
injury. SETTING: Sport concussion clinic within a regional tertiary care
hospital. MAIN OUTCOME MEASURES: Clinical outcomes including symptom severity,
symptom duration, age, time from injury-clinical presentation, sex, sport type,
previous concussion history, and whether or not they experienced loss of
consciousness or amnesia at the time of injury were recorded. Univariable
comparisons between those who did and did not report continuing play were
conducted. Multivariable linear regression models were constructed to identify
the independent association of continuing to play postinjury with symptom burden
and symptom recovery time, while controlling for the effect of potential
confounding variables. RESULTS: A total of 516 patients were included in the
study, assessed a mean of 12.1 +/- 5.2 days postinjury (35% female, mean age =
14.5 +/- 2.3 years). A total of 227 (44%) continued play after sustaining a
concussion. Continuing to play postconcussion was independently associated with
higher symptom severity during the initial clinical evaluation [beta-coefficient
= 6.144, 95% confidence interval (CI), 1.357-10.93], but not with symptom
duration evaluation (beta-coefficient = 1.794, 95% CI, -15.66 to 19.25).
CONCLUSION: Those who continued to play postconcussion presented with more severe
symptoms after injury. Recognition of suspected concussion and removal from play
on diagnosis confirmation may lead to better initial clinical outcomes after
concussion among child and adolescent athletes.
PMID- 29337723
TI - New Recommendations on Sport-Related Concussions: Stronger Methodology, Practical
Messages, and Remaining Challenges.
PMID- 29337724
TI - Statistical Significance Versus Clinical Importance of Observed Effect Sizes:
What Do P Values and Confidence Intervals Really Represent?
AB - Effect size measures are used to quantify treatment effects or associations
between variables. Such measures, of which >70 have been described in the
literature, include unstandardized and standardized differences in means, risk
differences, risk ratios, odds ratios, or correlations. While null hypothesis
significance testing is the predominant approach to statistical inference on
effect sizes, results of such tests are often misinterpreted, provide no
information on the magnitude of the estimate, and tell us nothing about the
clinically importance of an effect. Hence, researchers should not merely focus on
statistical significance but should also report the observed effect size.
However, all samples are to some degree affected by randomness, such that there
is a certain uncertainty on how well the observed effect size represents the
actual magnitude and direction of the effect in the population. Therefore, point
estimates of effect sizes should be accompanied by the entire range of plausible
values to quantify this uncertainty. This facilitates assessment of how large or
small the observed effect could actually be in the population of interest, and
hence how clinically important it could be. This tutorial reviews different
effect size measures and describes how confidence intervals can be used to
address not only the statistical significance but also the clinical significance
of the observed effect or association. Moreover, we discuss what P values
actually represent, and how they provide supplemental information about the
significant versus nonsignificant dichotomy. This tutorial intentionally focuses
on an intuitive explanation of concepts and interpretation of results, rather
than on the underlying mathematical theory or concepts.
PMID- 29337725
TI - In Response.
PMID- 29337726
TI - Valveless Trocar Systems and Respiratory Mechanics: Need for Revaluation.
PMID- 29337727
TI - Ultrasound in Anesthesia, Critical Care, and Pain Management: A Critic's Review.
PMID- 29337728
TI - Continuous Pulse Oximetry Does Not Measure Blood Pressure.
PMID- 29337729
TI - Evaluation of Almitrine Infusion During Veno-Venous Extracorporeal Membrane
Oxygenation for Severe Acute Respiratory Distress Syndrome in Adults.
AB - This single-center case series investigated the effect of almitrine infusion on
PaO2/fraction of inspired oxygen (FIO2) in 25 patients on veno-venous
extracorporeal membrane oxygenation for severe acute respiratory distress
syndrome. A positive trial was defined as an increase of PaO2/FIO2 ratio >=20%.
Thirty-two trials were performed. Twenty (62.5%, 95% confidence interval, 37.5%
75%) trials in 18 patients were positive, with a median PaO2/FIO2 ratio increase
of 35% (25%-43%). A focal acute respiratory distress syndrome and inhaled nitric
oxide therapy were more frequent in patients with a positive response to
almitrine. We observed no complications of almitrine use.
PMID- 29337730
TI - Effects of Electrical Transcutaneous Vagus Nerve Stimulation on the Perceived
Intensity of Repetitive Painful Heat Stimuli: A Blinded Placebo- and Sham
Controlled Randomized Crossover Investigation.
AB - BACKGROUND: Transcutaneous vagus nerve stimulation (TVNS) is a promising
treatment for acute and chronic pain. However, experimental studies yielded
controversial results. We examined if TVNS reduces the perceived intensity of
repetitive painful heat stimulation and temporal summation of pain (TSP) in
healthy volunteers in comparison with placebo and sham stimulation, as well as no
intervention. METHODS: In 4 sessions, 90 heat pulse stimuli at individual pain
tolerance temperature were applied to the ventral forearm of 49 healthy
volunteers (25 women) using a Contact Heat Evoked Potential Stimulator thermode
(Medoc, Ramat Yishai, Israel). Pain intensity was assessed with verbal ratings on
a numeric pain scale (0-100) at every tenth heat pulse. After the first session
in which pain intensities without intervention were evaluated, participants
completed 3 sessions in a single-blinded randomized crossover manner: (1) sham
stimulation applied at the earlobes, (2) placebo stimulation (inactive device),
or (3) TVNS applied at the cymbas conchae. Primary data were analyzed using
analysis of variance for repeated measures and t test for paired samples.
RESULTS: Pain intensity decreased during all interventions as compared to no
intervention (etap = 0.22, P < .001; mean difference TVNS versus no intervention
9.5; 95% confidence interval [CI], 3.6-15.4; P < .001). Hypoalgesic effect of
TVNS was better than that of placebo and sham in men before the onset of TSP
(mean differences for TVNS versus placebo 6.2; 95% CI, 0.2-12.1; TVNS versus sham
6.2; 95% CI, 0.2-12.1; P < .05). In women, TSP response under TVNS was decreased
if compared to no intervention (median difference, 7.5; 95% CI, 3.5-15.0; P =
.003). CONCLUSIONS: TVNS, placebo, and sham stimulation exerted comparable
effects under experimental heat pain stimulation. Only in male participants, TVNS
was superior to sham and placebo conditions in the reduction of heat pain before
the onset of TSP.
PMID- 29337731
TI - In Response.
PMID- 29337738
TI - Decision Support Alerts: Importance of Validation.
PMID- 29337740
TI - Risk Prediction Tools: The Need for Greater Transparency.
PMID- 29337741
TI - Regulatory Landscape for Clinical Decision Support Technology.
PMID- 29337743
TI - Impact of a Novel Multiparameter Decision Support System on Intraoperative
Processes of Care and Postoperative Outcomes.
AB - BACKGROUND: The authors hypothesized that a multiparameter intraoperative
decision support system with real-time visualizations may improve processes of
care and outcomes. METHODS: Electronic health record data were retrospectively
compared over a 6-yr period across three groups: experimental cases, in which the
decision support system was used for 75% or more of the case at sole discretion
of the providers; parallel controls (system used 74% or less); and historical
controls before system implementation. Inclusion criteria were adults under
general anesthesia, advanced medical disease, case duration of 60 min or longer,
and length of stay of two days or more. The process measures were avoidance of
intraoperative hypotension, ventilator tidal volume greater than 10 ml/kg, and
crystalloid administration (ml . kg . h). The secondary outcome measures were
myocardial injury, acute kidney injury, mortality, length of hospital stay, and
encounter charges. RESULTS: A total of 26,769 patients were evaluated: 7,954
experimental cases, 10,933 parallel controls, and 7,882 historical controls.
Comparing experimental cases to parallel controls with propensity score
adjustment, the data demonstrated the following medians, interquartile ranges,
and effect sizes: hypotension 1 (0 to 5) versus 1 (0 to 5) min, P < 0.001, beta =
-0.19; crystalloid administration 5.88 ml . kg . h (4.18 to 8.18) versus 6.17
(4.32 to 8.79), P < 0.001, beta = -0.03; tidal volume greater than 10 ml/kg 28%
versus 37%, P < 0.001, adjusted odds ratio 0.65 (0.53 to 0.80); encounter charges
$65,770 ($41,237 to $123,869) versus $69,373 ($42,101 to $132,817), P < 0.001,
beta = -0.003. The secondary clinical outcome measures were not significantly
affected. CONCLUSIONS: The use of an intraoperative decision support system was
associated with improved process measures, but not postoperative clinical
outcomes.
PMID- 29337744
TI - Defining the Intrinsic Cardiac Risks of Operations to Improve Preoperative
Cardiac Risk Assessments.
AB - BACKGROUND: Current preoperative cardiac risk stratification practices group
operations into broad categories, which might inadequately consider the intrinsic
cardiac risks of individual operations. We sought to define the intrinsic cardiac
risks of individual operations and to demonstrate how grouping operations might
lead to imprecise estimates of perioperative cardiac risk. METHODS: Elective
operations (based on Common Procedural Terminology codes) performed from January
1, 2010 to December 31, 2015 at hospitals participating in the American College
of Surgeons National Surgical Quality Improvement Program were studied. A
composite measure of perioperative adverse cardiac events was defined as either
cardiac arrest requiring cardiopulmonary resuscitation or acute myocardial
infarction. Operations' intrinsic cardiac risks were derived from mixed-effects
models while controlling for patient mix. Resultant risks were sorted into low-,
intermediate-, and high-risk categories, and the most commonly performed
operations within each category were identified. Intrinsic operative risks were
also examined using a representative grouping of operations to portray within
group variation. RESULTS: Sixty-six low, 30 intermediate, and 106 high intrinsic
cardiac risk operations were identified. Excisional breast biopsy had the lowest
intrinsic cardiac risk (overall rate, 0.01%; odds ratio, 0.11; 95% CI, 0.02 to
0.25) relative to the average, whereas aorto-bifemoral bypass grafting had the
highest (overall rate, 4.1%; odds ratio, 6.61; 95% CI, 5.54 to 7.90). There was
wide variation in the intrinsic cardiac risks of operations within the
representative grouping (median odds ratio, 1.40; interquartile range, 0.88 to
2.17). CONCLUSIONS: A continuum of intrinsic cardiac risk exists among
operations. Grouping operations into broad categories inadequately accounts for
the intrinsic cardiac risk of individual operations.
PMID- 29337748
TI - Avoidance of Hyperoxemia during Cardiopulmonary Bypass: Why Does Pathophysiology
Not Always Translate into Clinical Outcome?
PMID- 29337749
TI - Clinical Technology and Glucose Management.
PMID- 29337750
TI - In Reply.
PMID- 29337751
TI - Perioperative Pain Management for Total Knee Arthroplasty: Need More Focus on the
Forest and Less on the Trees.
PMID- 29337752
TI - In Reply.
PMID- 29337753
TI - Solvent Matters!
PMID- 29337754
TI - In Reply.
PMID- 29337755
TI - Distal Subclavian Cannulation and Extravasation.
PMID- 29337756
TI - Taller People Should Have as Their Normal a Higher Body Mass Index.
PMID- 29337757
TI - Unusual Catheter Placement on Chest Radiograph: Two Dimensions, Two Possible
Locations (or More).
PMID- 29337758
TI - In Reply.
PMID- 29337761
TI - Children's Recognition of Emotional Prosody in Spectrally Degraded Speech Is
Predicted by Their Age and Cognitive Status.
AB - OBJECTIVES: It is known that school-aged children with cochlear implants show
deficits in voice emotion recognition relative to normal-hearing peers. Little,
however, is known about normal-hearing children's processing of emotional cues in
cochlear implant-simulated, spectrally degraded speech. The objective of this
study was to investigate school-aged, normal-hearing children's recognition of
voice emotion, and the degree to which their performance could be predicted by
their age, vocabulary, and cognitive factors such as nonverbal intelligence and
executive function. DESIGN: Normal-hearing children (6-19 years old) and young
adults were tested on a voice emotion recognition task under three different
conditions of spectral degradation using cochlear implant simulations (full
spectrum, 16-channel, and 8-channel noise-vocoded speech). Measures of
vocabulary, nonverbal intelligence, and executive function were obtained as well.
RESULTS: Adults outperformed children on all tasks, and a strong developmental
effect was observed. The children's age, the degree of spectral resolution, and
nonverbal intelligence were predictors of performance, but vocabulary and
executive functions were not, and no interactions were observed between age and
spectral resolution. CONCLUSIONS: These results indicate that cognitive function
and age play important roles in children's ability to process emotional prosody
in spectrally degraded speech. The lack of an interaction between the degree of
spectral resolution and children's age further suggests that younger and older
children may benefit similarly from improvements in spectral resolution. The
findings imply that younger and older children with cochlear implants may benefit
similarly from technical advances that improve spectral resolution.
PMID- 29337760
TI - Using Thresholds in Noise to Identify Hidden Hearing Loss in Humans.
AB - OBJECTIVES: Recent animal studies suggest that noise-induced synaptopathy may
underlie a phenomenon that has been labeled hidden hearing loss (HHL). Noise
exposure preferentially damages low spontaneous-rate auditory nerve fibers, which
are involved in the processing of moderate- to high-level sounds and are more
resistant to masking by background noise. Therefore, the effect of synaptopathy
may be more evident in suprathreshold measures of auditory function, especially
in the presence of background noise. The purpose of this study was to develop a
statistical model for estimating HHL in humans using thresholds in noise as the
outcome variable and measures that reflect the integrity of sites along the
auditory pathway as explanatory variables. Our working hypothesis is that HHL is
evident in the portion of the variance observed in thresholds in noise that is
not dependent on thresholds in quiet, because this residual variance retains
statistical dependence on other measures of suprathreshold function. DESIGN:
Study participants included 13 adults with normal hearing (<=15 dB HL) and 20
adults with normal hearing at 1 kHz and sensorineural hearing loss at 4 kHz (>15
dB HL). Thresholds in noise were measured, and the residual of the correlation
between thresholds in noise and thresholds in quiet, which we refer to as
thresholds-in-noise residual, was used as the outcome measure for the model.
Explanatory measures were as follows: (1) auditory brainstem response (ABR) waves
I and V amplitudes; (2) electrocochleographic action potential and summating
potential amplitudes; (3) distortion product otoacoustic emissions level; and (4)
categorical loudness scaling. All measurements were made at two frequencies (1
and 4 kHz). ABR and electrocochleographic measurements were made at 80 and 100 dB
peak equivalent sound pressure level, while wider ranges of levels were tested
during distortion product otoacoustic emission and categorical loudness scaling
measurements. A model relating the thresholds-in-noise residual and the
explanatory measures was created using multiple linear regression analysis.
RESULTS: Predictions of thresholds-in-noise residual using the model accounted
for 61% (p < 0.01) and 48% (p < 0.01) of the variance in the measured thresholds
in-noise residual at 1 and 4 kHz, respectively. CONCLUSIONS: Measures of
thresholds in noise, the summating potential to action potential ratio, and ABR
waves I and V amplitudes may be useful for the prediction of HHL in humans. With
further development, our approach of quantifying HHL by the variance that remains
in suprathreshold measures of auditory function after removing the variance due
to thresholds in quiet, together with our statistical modeling, may provide a
quantifiable and verifiable estimate of HHL in humans with normal hearing and
with hearing loss. The current results are consistent with the view that inner
hair cell and auditory nerve pathology may underlie suprathreshold auditory
performance.
PMID- 29337762
TI - Tinnitus and Auditory Perception After a History of Noise Exposure: Relationship
to Auditory Brainstem Response Measures.
AB - OBJECTIVES: To determine whether auditory brainstem response (ABR) wave I
amplitude is associated with measures of auditory perception in young people with
normal distortion product otoacoustic emissions (DPOAEs) and varying levels of
noise exposure history. DESIGN: Tinnitus, loudness tolerance, and speech
perception ability were measured in 31 young military Veterans and 43 non
Veterans (19 to 35 years of age) with normal pure-tone thresholds and DPOAEs.
Speech perception was evaluated in quiet using Northwestern University Auditory
Test (NU-6) word lists and in background noise using the words in noise (WIN)
test. Loudness discomfort levels were measured using 1-, 3-, 4-, and 6-kHz pulsed
pure tones. DPOAEs and ABRs were collected in each participant to assess outer
hair cell and auditory nerve function. RESULTS: The probability of reporting
tinnitus in this sample increased by a factor of 2.0 per 0.1 uV decrease in ABR
wave I amplitude (95% Bayesian confidence interval, 1.1 to 5.0) for males and by
a factor of 2.2 (95% confidence interval, 1.0 to 6.4) for females after adjusting
for sex and DPOAE levels. Similar results were obtained in an alternate model
adjusted for pure-tone thresholds in addition to sex and DPOAE levels. No
apparent relationship was found between wave I amplitude and either loudness
tolerance or speech perception in quiet or noise. CONCLUSIONS: Reduced ABR wave I
amplitude was associated with an increased risk of tinnitus, even after adjusting
for DPOAEs and sex. In contrast, wave III and V amplitudes had little effect on
tinnitus risk. This suggests that changes in peripheral input at the level of the
inner hair cell or auditory nerve may lead to increases in central gain that give
rise to the perception of tinnitus. Although the extent of synaptopathy in the
study participants cannot be measured directly, these findings are consistent
with the prediction that tinnitus may be a perceptual consequence of cochlear
synaptopathy.
PMID- 29337764
TI - A National Accreditation Program for Rectal Cancer: A Long and Winding Road.
PMID- 29337765
TI - Digestive Tract Damage: A Predictor of Early Surgical Intervention in Patients
With Newly Diagnosed Crohn's Disease.
PMID- 29337763
TI - The Effect of Simulated Interaural Frequency Mismatch on Speech Understanding and
Spatial Release From Masking.
AB - OBJECTIVE: The binaural-hearing system interaurally compares inputs, which
underlies the ability to localize sound sources and to better understand speech
in complex acoustic environments. Cochlear implants (CIs) are provided in both
ears to increase binaural-hearing benefits; however, bilateral CI users continue
to struggle with understanding speech in the presence of interfering sounds and
do not achieve the same level of spatial release from masking (SRM) as normal
hearing listeners. One reason for diminished SRM in CI users could be that the
electrode arrays are inserted at different depths in each ear, which would cause
an interaural frequency mismatch. Because interaural frequency mismatch
diminishes the salience of interaural differences for relatively simple stimuli,
it may also diminish binaural benefits for spectral-temporally complex stimuli
like speech. This study evaluated the effect of simulated frequency-to-place
mismatch on speech understanding and SRM. DESIGN: Eleven normal-hearing listeners
were tested on a speech understanding task. There was a female target talker who
spoke five-word sentences from a closed set of words. There were two interfering
male talkers who spoke unrelated sentences. Nonindividualized head-related
transfer functions were used to simulate a virtual auditory space. The target was
presented from the front (0 degrees ), and the interfering speech was either
presented from the front (colocated) or from 90 degrees to the right (spatially
separated). Stimuli were then processed by an eight-channel vocoder with tonal
carriers to simulate aspects of listening through a CI. Frequency-to-place
mismatch ("shift") was introduced by increasing the center frequency of the
synthesis filters compared with the corresponding analysis filters. Speech
understanding was measured for different shifts (0, 3, 4.5, and 6 mm) and target
to-masker ratios (TMRs: +10 to -10 dB). SRM was calculated as the difference in
the percentage of correct words for the colocated and separated conditions. Two
types of shifts were tested: (1) bilateral shifts that had the same frequency-to
place mismatch in both ears, but no interaural frequency mismatch, and (2)
unilateral shifts that produced an interaural frequency mismatch. RESULTS: For
the bilateral shift conditions, speech understanding decreased with increasing
shift and with decreasing TMR, for both colocated and separate conditions. There
was, however, no interaction between shift and spatial configuration; in other
words, SRM was not affected by shift. For the unilateral shift conditions, speech
understanding decreased with increasing interaural mismatch and with decreasing
TMR for both the colocated and spatially separated conditions. Critically, there
was a significant interaction between the amount of shift and spatial
configuration; in other words, SRM decreased for increasing interaural mismatch.
CONCLUSIONS: A frequency-to-place mismatch in one or both ears resulted in
decreased speech understanding. SRM, however, was only affected in conditions
with unilateral shifts and interaural frequency mismatch. Therefore, matching
frequency information between the ears provides listeners with larger binaural
hearing benefits, for example, improved speech understanding in the presence of
interfering talkers. A clinical procedure to reduce interaural frequency mismatch
when programming bilateral CIs may improve benefits in speech segregation that
are due to binaural-hearing abilities.
PMID- 29337766
TI - Worrying About Postoperative Functional Outcomes in Young Women With Colorectal
Endometriosis: That's It!
PMID- 29337767
TI - Presacral (Retrorectal) Tumors: Optimizing the Management Strategy.
PMID- 29337768
TI - Expert Commentary on Presacral Tumors.
PMID- 29337769
TI - Morbidity Following Coloanal Anastomosis: A Comparison of Colonic J-Pouch vs
Straight Anastomosis.
AB - BACKGROUND: Low rectal tumors are often treated with sphincter-preserving
resection followed by coloanal anastomosis. OBJECTIVE: The purpose of this study
was to compare the short-term complications following straight coloanal
anastomosis vs colonic J-pouch anal anastomosis. DESIGN: Patients were identified
who underwent proctectomy for rectal neoplasia followed by coloanal anastomosis
in the 2008 to 2013 American College of Surgeons National Surgical Quality
Improvement Program database. Demographic characteristics and 30-day
postoperative complications were compared between groups. SETTINGS: A national
sample was extracted from the American College of Surgeons National Surgical
Quality Improvement Project database. PATIENTS: Inpatients following proctectomy
and coloanal anastomosis for rectal cancer were selected. MAIN OUTCOME MEASURES:
Demographic characteristics and 30-day postoperative complications were compared
between the 2 groups. RESULTS: One thousand three hundred seventy patients were
included, 624 in the straight anastomosis group and 746 in the colonic J-pouch
group. Preoperative characteristics were similar between groups, with the
exception of preoperative radiation therapy (straight anastomosis 35% vs colonic
J-pouch 48%, p = 0.0004). Univariate analysis demonstrated that deep surgical
site infection (3.7% vs 1.4%, p = 0.01), septic shock (2.25% vs 0.8%, p = 0.04),
and return to the operating room (8.8% vs 5.0%, p = 0.0006) were more frequent in
the straight anastomosis group vs the colonic J-pouch group. Major complications
were also higher (23% vs 14%, p = 0.0001) and length of stay was longer in the
straight anastomosis group vs the colonic J-pouch group (8.9 days vs 8.1 days, p
= 0.02). After adjusting for covariates, major complications were less following
colonic J-pouch vs straight anastomosis (OR, 0.57; CI, 0.38-0.84; p = 0.005).
Subgroup analysis of patients who received preoperative radiation therapy
demonstrated no difference in major complications between groups. LIMITATIONS:
This study had those limitations inherent to a retrospective study using an
inpatient database. CONCLUSION: Postoperative complications were less following
colonic J-pouch anastomosis vs straight anastomosis. Patients who received
preoperative radiation had similar rates of complications, regardless of the
reconstructive technique used following low anterior resection. See Video
Abstract at http://links.lww.com/DCR/A468.
PMID- 29337770
TI - Survival Benefit of Japanese Extended Lymphadenectomy for Clinically Node
Negative and Node-Positive Colorectal Cancers.
AB - BACKGROUND: The impact of extended lymphadenectomy for colorectal cancer is still
not sufficiently clear. OBJECTIVE: The aim of the present study was to evaluate
the survival benefit of extended lymphadenectomy compared with nonextended
lymphadenectomy for clinically node-negative and node-positive colorectal
cancers. DESIGN: The present study was a retrospective cohort study that used
prospectively collected data and a propensity score matching method. SETTINGS:
The present study was conducted at a single specialized colorectal surgery
department. PATIENTS: Of the 1314 patients who underwent radical resection with
nonextended or extended lymphadenectomy between 1988 and 2007, we included 711
and 603 patients in the cN0 and cN1/2 series. Propensity score matching was
applied, and 141 and 63 pairs were extracted from the cN0 and cN1/2 series. MAIN
OUTCOME MEASURES: Disease-free survival, cancer-specific survival, and overall
survival of the 2 groups were calculated and compared. RESULTS: In the cN0
series, no differences were observed in the long-term outcomes between the
nonextended and extended groups. In the cN1/2 series, the disease-free survival,
cancer-specific survival and overall survival were significantly higher (log
rank, p = 0.04, p = 0.02, and p = 0.01, respectively), and the frequency of local
recurrence was significantly lower (p = 0.04) in the extended group. LIMITATIONS:
The present study was limited by its nonrandomized retrospective design.
CONCLUSIONS: Extended lymphadenectomy demonstrated a good inhibitory effect on
the local recurrence rate and led to improved disease-free survival, cancer
specific survival, and overall survival of patients in the cN1/2 series. See
Video Abstract at http://links.lww.com/DCR/A517.
PMID- 29337771
TI - Outcomes of Closed Versus Open Defects After Local Excision of Rectal Neoplasms:
A Multi-institutional Matched Analysis.
AB - BACKGROUND: The management of the rectal wall defect after local excision of
rectal neoplasms remains controversial, and the existing data are equivocal.
OBJECTIVE: This study aimed to determine the effect of open versus closed defects
on postoperative outcomes after local excision of rectal neoplasms. DESIGN: Data
from 3 institutions were analyzed. Propensity score matching was performed in one
to-one fashion to create a balanced cohort comparing open and closed defects.
SETTINGS: This study was conducted at high-volume specialist referral hospitals.
PATIENTS: Adult patients undergoing local excision via transanal endoscopic
surgery from 2004 to 2016 were included. Patients were assigned to open- and
closed-defect groups, and further stratified by full- or partial-thickness
excision. INTERVENTION: Closure of the rectal wall defect was performed at the
surgeon's discretion. MAIN OUTCOME MEASURES: The primary outcome measured was the
incidence of 30-day complications. RESULTS: A total of 991 patients were eligible
(593 full-thickness excision with 114 open and 479 closed, and 398 partial
thickness excision with 263 open and 135 closed). After matching, balanced
cohorts consisting of 220 patients with full-thickness excision and 210 patients
with partial-thickness excision were created. Operative time was similar for open
and closed defects for both full-and partial-thickness excision. The incidence of
30-day complications was similar for open and closed defects after full- (15% vs.
12%, p = 0.432) and partial-thickness excision (7% vs 5%, p = 0.552). The total
number of complications was also similar after full- or partial-thickness
excision. Patients undergoing full-thickness excision with open defects had a
higher incidence of clinically significant bleeding complications (9% vs 3%, p =
0.045). LIMITATIONS: Data were obtained from 3 institutions with different
equipment and perioperative management over a long time period. CONCLUSIONS:
There was no difference in overall complications between open and closed defects
for patients undergoing local excision of rectal neoplasms, but there may be more
bleeding complications in open defects after full-thickness excision. A selective
approach to defect closure may be appropriate. See Video Abstract at
http://links.lww.com/DCR/A470.
PMID- 29337772
TI - Salvage Surgery for Locoregional Failure in Anal Squamous Cell Carcinoma.
AB - BACKGROUND: Anal squamous cell carcinoma is a rare cancer with a high cure rate,
making research into the treatment of locoregional failure difficult. OBJECTIVE:
The purpose of this study was to examine factors related to local treatment
failure and determine the outcomes of patients undergoing local salvage
resection. DESIGN: This was a retrospective cohort study. SETTING: This study was
conducted at a quaternary referral center. PATIENTS: Patients with anal squamous
cell carcinoma treated with chemoradiotherapy between January 1983 and December
2015 were included. MAIN OUTCOME MEASURES: The influence of patient-, tumor-, and
treatment-related factors on the primary outcome measures of locoregional
failure, overall survival, and disease-free survival were investigated. RESULTS:
Of 467 patients with anal squamous cell carcinoma, 63 experienced locoregional
failure with 41 undergoing salvage resection. Twenty-seven patients (38%) had
persistent disease and 36 (62%) developed locoregional recurrence. Multivariate
analysis identified tumor stage (HR, 3.16; p < 0.002) as an independent predictor
of locoregional failure. Thirty abdominoperineal resections and 11 pelvic
exenterations were undertaken with no surgical mortality. At a median follow-up
of 20 months (range, 4-150 months), 5-year overall and disease-free survival for
the salvage cohort was 51% and 47%. Margin positivity was an independent
predictor for relapse post-salvage surgery on multivariate analysis (HR, 20.1; p
= 0.027). Nineteen patients (48%) developed further relapse, which included all
10 patients with a positive resection margin, 3 of whom underwent re-resection.
Of the 19 patients with relapse, 3 remain alive and 2 have persistent disease.
LIMITATIONS: Limitations include the retrospective nature of the database, the
prolonged time period of the study, and episodes of incomplete data. CONCLUSIONS:
Advanced T stage is an independent predictor of local failure in anal squamous
cell carcinoma. Most patients can be salvaged, with a positive resection margin
being a strong predictor of further relapse and poor outcome. See Video Abstract
at http://links.lww.com/DCR/A515.
PMID- 29337773
TI - Prognostic Factors for Locoregional Recurrence in Neuroendocrine Tumors of the
Rectum.
AB - BACKGROUND: Optimal management of rectal neuroendocrine tumors is not yet well
defined. Various pathologic factors, particularly tumor size, have been proposed
as prognostic markers. OBJECTIVE: We characterized sequential patients diagnosed
with rectal neuroendocrine tumors in a population-based setting to determine
whether tumor size and other pathologic markers could be useful in guiding
locoregional management. DESIGN: This study is a retrospective analysis of data
from the British Columbia provincial cancer registry. SETTINGS: The study was
conducted at a tertiary care center. PATIENTS: Sequential patients diagnosed with
rectal neuroendocrine tumors between 1999 and 2011 were identified.
Neuroendocrine tumors were classified as G1 and G2 tumors with a Ki-67 <=20%
and/or mitotic count <=20 per high-power field. MAIN OUTCOME MEASURES: Baseline
clinicopathologic data including TNM staging, depth of invasion, tumor size,
treatment modalities, and outcomes including survival data were measured.
RESULTS: Of 91 rectal neuroendocrine tumors, the median patient age was 58 years,
and 35 were men. Median tumor size was 6 mm. Median length of follow-up was 58.1
months, with 3 patients presenting with stage IV disease. Treatment included
local ablation (n = 5), local excision (n = 79), surgical resection (n = 4), and
pelvic radiation (n = 1; T3N1 tumor). Final margin status was positive in 17
cases. Local relapse occurred in 8 cases and 1 relapse to bone 13 months after
T3N1 tumor resection. Univariate analysis demonstrated an association between
local relapse and Ki-67, mitotic count, grade, and lymphovascular invasion (p <
0.01). Larger tumor size was associated with decreased disease-free survival.
LIMITATIONS: Sample size was 91 patients in the whole provincial population over
a 13-year time period because of the low incidence of rectal neuroendocrine
tumors. CONCLUSIONS: In this population-based cohort, rectal neuroendocrine
tumors generally presented with small, early tumors and were treated with local
excision or surgical resection without pelvic radiation. Pathologic markers play
a role in risk stratification and prognostication. See Video Abstract at
http://links.lww.com/DCR/A514.
PMID- 29337775
TI - Comparisons of Rigid Proctoscopy, Flexible Colonoscopy, and Digital Rectal
Examination for Determining the Localization of Rectal Cancers.
AB - BACKGROUND: Rigid proctoscopy is considered essential for rectal tumor
localization, although the current gold standard for detection of colorectal
cancers is colonoscopy. The European Society for Medical Oncology Guidelines
indicate that rigid and flexible endoscopies afford essentially identical
results, although little evidence is yet available to support this. OBJECTIVE:
The purpose of this study was to determine the accuracy of colonoscopy in
identifying the location of rectal cancer and to compare the results with those
of rigid proctoscopy and digital rectal examination. DESIGN: This was a
retrospective analysis of a prospective database. SETTINGS: The study was
conducted at a single tertiary colorectal surgery referral center. PATIENTS: A
total of 173 patients scheduled for curative surgery for histologically verified
rectal adenocarcinoma between December 2009 and February 2015 were entered into
the study, after having given informed consent. MAIN OUTCOME MEASURES: The main
study measure was the mean difference and limits of agreement in assessment of
the height of the distal edge of rectal cancer from the anal verge, using the
Bland and Altman method. RESULTS: The mean difference between rigid proctoscopy
and flexible colonoscopy was -0.2 cm (95% CI, -2.0 to 1.6 cm). The mean
difference between rigid proctoscopy and digital rectal examination was 0.3 cm
(95% CI, 1.9 to 2.4 cm). Intermethod variability larger than the 95% CI between
rigid and flexible endoscopes was correlated to the tumor height (OR, 4.27 (95%
CI, 1.84-3.10); p = 0.021). LIMITATIONS: This study was conducted in a single
center. CONCLUSIONS: The limits of agreement (-2.0 and 1.6 cm) in identifying the
height of rectal cancers from the anal verge are sufficiently small to support
the view that flexible colonoscopy provides similar tumor locations to those
measured by rigid proctoscopy, although the discrepancy occasionally exceeded 2
cm for tumors >5 cm above the anal verge. See Video Abstract at
http://links.lww.com/DCR/A405.
PMID- 29337774
TI - Gadolinium-Based Contrast Agent During Pelvic MRI: Contribution to Patient
Management in Rectal Cancer.
AB - BACKGROUND: Few publications exist regarding gadolinium-enhanced sequences in
rectal MRI. None have evaluated its potential impact on patient management.
OBJECTIVE: This study aimed to assess whether gadolinium-enhanced sequences,
including dynamic contrast enhancement, change radiologic interpretation and
clinical management of rectal cancer. DESIGN: This is a retrospective analysis of
100 rectal MRIs (50 baseline and 50 postneoadjuvant treatment), both without and
with gadolinium-enhanced sequences. Treatment plans were rendered based on each
radiologic interpretation for each case by a single experienced surgeon.
Differences in radiologic interpretation and management were statistically
analyzed. SETTINGS: The study was conducted at the Memorial Sloan Kettering
Cancer Center. PATIENTS: Patients undergoing rectal MRI between 2011 and 2015 for
baseline tumor staging and/or postneoadjuvant restaging were included. MAIN
OUTCOME MEASURES: Primary outcome measures were changes in radiologic tumor
stage, tumor margins, and surgical planning with the use of gadolinium at
baseline and postneoadjuvant time points. RESULTS: At baseline, tumor downstaging
occurred in 8 (16%) of 50 and upstaging in 4 (8%) of 50 with gadolinium.
Postneoadjuvant treatment, upstaging occurred in 1 (2%) of 50 from T2 to T3a. At
baseline, mean distances from tumor to anorectal ring, anal verge, and mesorectal
fascia were not statistically different with gadolinium. However, in 7 patients,
differences could have resulted in treatment changes, accounted for by changes in
relationships to anterior peritoneal reflection (n = 4), anorectal ring (n = 2),
or anal verge (n = 1). Postneoadjuvant treatment, distances to anorectal ring and
anal verge (in centimeters) were statistically smaller with gadolinium (p =
0.0017 and p = 0.0151) but could not have resulted in clinically significant
treatment changes. LIMITATIONS: This study was limited by its retrospective
design. CONCLUSIONS: The use of gadolinium at baseline MRI could have altered
treatment in 24% of patients because of differences in tumor stage or position.
Postneoadjuvant treatment, gadolinium resulted in statistically smaller distances
to sphincters, which could influence surgical decision for sphincter-preserving
rectal resection. See Video Abstract at http://links.lww.com/DCR/A444.
PMID- 29337776
TI - Lemann Index at Diagnosis Predicts the Risk of Early Surgery in Crohn's Disease.
AB - BACKGROUND: Identifying patients with Crohn's disease with rapid disease progress
or high risk of early surgery is crucial to clinical decision making. OBJECTIVE:
The aim was to evaluate the correlation between the Lemann index at diagnosis and
abdominal surgery in the first year after Crohn's disease diagnosis and to find
the risk factors for early surgery. DESIGN: This was a retrospective cohort
study. SETTINGS: The study was conducted at a single tertiary hospital. PATIENTS:
Patients diagnosed with Crohn's disease between 2013 and 2015 in our center were
included. MAIN OUTCOME MEASURES: The outcome of interest was the need for an
abdominal surgery within 1 year after the Lemann index evaluation at diagnosis.
RESULTS: Of 212 eligible patients, 48 patients underwent abdominal surgery during
follow-up. Lemann index was much higher in the surgery group (5.3 vs 2.6; p <
0.001). On tertiles of the Lemann index, the frequency of surgery grew (2.8%,
9.9%, and 55.7%; p < 0.001) as the Lemann index increased. The receiver operating
characteristic curve was constructed taking into account the Lemann index for
selecting patients with a high risk of surgery. Specificity, sensitivity, and
area under receiver operating characteristic curve were 84.8%, 81.3%, and 0.89 of
the Lemann Index at a cutoff level of 3.7. Patients with Lemann index >=3.7
carried a higher risk of abdominal surgery (OR = 18.6; p < 0.001). Stricturing
and penetrating disease were predictors for abdominal surgery, whereas antitumor
necrosis factor treatment was associated with a significant reduction of surgical
requirements. LIMITATIONS: This study was limited by its retrospective design.
The ability of the Lemann index to predict the long-term risk of surgery was
unknown. CONCLUSIONS: Lemann index at diagnosis is a reliable index to predict
the risk of abdominal surgery in the first year after diagnosis of Crohn's
disease. Patients with a high Lemann index might need closer follow-up or
aggressive medical therapy. See Video Abstract at http://links.lww.com/DCR/A518.
PMID- 29337777
TI - Rescue Diverting Loop Ileostomy: An Alternative to Emergent Colectomy in the
Setting of Severe Acute Refractory IBD-Colitis.
AB - BACKGROUND: Severe acute refractory colitis has traditionally been an indication
for emergent colectomy in IBD, yet under these circumstances patients are at
elevated risk for complications because of their heightened inflammatory state,
nutritional deficiencies, and immunocompromised state. OBJECTIVE: We hypothesized
that rescue diverting loop ileostomy may be a viable alternative to emergent
colectomy, providing the opportunity for colonic healing and patient optimization
before more definitive surgery. DESIGN: This was a retrospective case series.
SETTINGS: The study was conducted at a single academic center. PATIENTS: Patients
with severe acute medically refractory IBD-related colitis were included.
INTERVENTION: Rescue diverting loop ileostomy was the intervening procedure. MAIN
OUTCOME MEASURES: The primary outcome was avoidance of urgent/emergent colectomy.
The secondary outcome was efficacy, defined by 3 clinical aims: 1) reduced
steroid dependence or opportunity for bridge to medical rescue, 2) improved
nutritional status, and 3) ability to undergo an elective laparoscopic definitive
procedure or ileostomy reversal with colon salvage. RESULTS: Among 33 patients,
14 had Crohn's disease and 19 had ulcerative colitis. Three patients required
urgent/emergent colectomy, 2 with ulcerative colitis and 1 with Crohn's disease.
Across both disease cohorts, >80% of patients achieved each clinical aim for
efficacy: 88% reduced their steroid dependence or were able to bridge to medical
rescue, 87% improved their nutritional status, and 82% underwent an elective
laparoscopic definitive procedure or ileostomy reversal. A total of 4 patients
(11.7%) experienced a postoperative complication following diversion, including 3
surgical site infections and 1 episode of acute kidney injury. LIMITATIONS: The
study was limited by being a single-center, retrospective series. CONCLUSIONS:
Rescue diverting loop ileostomy in the setting of severe, refractory IBD-colitis
is a safe and effective alternative to emergent colectomy. This procedure has
acceptably low complication rates and affords patients time for medical and
nutritional optimization before definitive surgical intervention. See Video
Abstract at http://links.lww.com/DCR/A520.
PMID- 29337779
TI - Does Ventral Rectopexy Improve Pelvic Floor Function in the Long Term?
AB - BACKGROUND: Information is needed on long-term functional results, sequelas, and
outcome predictors for laparoscopic ventral mesh rectopexy. OBJECTIVE: The
purpose of this study was to evaluate long-term function postventral rectopexy in
patients with external rectal prolapse or internal rectal prolapse in a large
cohort and to identify the possible effects of patient-related factors and
operative technical details on patient-reported outcomes. DESIGN: This was a
retrospective review with a cross-sectional questionnaire study. SETTINGS: Data
were collated from prospectively collected registries in 2 university and 2
central hospitals in Finland. PATIENTS: All 508 consecutive patients treated with
ventral rectopexy for external rectal prolapse or symptomatic internal rectal
prolapse in 2005 to 2013 were included. INTERVENTIONS: A questionnaire concerning
disease-related symptoms and effect on quality of life was used. MAIN OUTCOME
MEASURES: Defecatory function measured by the Wexner score, the obstructive
defecation score, and subjective symptom and quality-of-life evaluation using the
visual analog scale were included. The effects of patient-related factors and
operative technical details were assessed using multivariate analysis. RESULTS:
The questionnaire response rate was 70.7% (330/467 living patients) with a median
follow-up time of 44 months. The mean Wexner scores were 7.0 (SD = 6.1) and 6.9
(SD = 5.6), and the mean obstructive defecation scores were 9.7 (SD = 7.6) and
12.3 (SD = 8.0) for patients presenting with external rectal prolapse and
internal rectal prolapse. Subjective symptom relief was experienced by 76% and
reported more often by patients with external rectal prolapse than with internal
rectal prolapse (86% vs 68%; p < 0.001). Complications occurred in 11.4% of
patients, and the recurrence rate for rectal prolapse was 7.1%. LIMITATIONS: This
study was limited by its lack of preoperative functional data and suboptimal
questionnaire response rate. CONCLUSIONS: Ventral mesh rectopexy effectively
treats posterior pelvic floor dysfunction with a low complication rate and an
acceptable recurrence rate. Patients with external rectal prolapse benefit more
from the operation than those with symptomatic internal rectal prolapse. See
Video Abstract at http://links.lww.com/DCR/A479.
PMID- 29337778
TI - Pelvic Pain and Quality of Life Before and After Laparoscopic Bowel Resection for
Rectosigmoid Endometriosis: A Prospective, Observational Study.
AB - BACKGROUND: Surgery for rectosigmoid endometriosis carries a substantial risk of
short- and long-term complications, which has to be counterbalanced against the
potential effect of the procedure. Prospective data are scarce in the field of
deep infiltrating endometriosis surgery. OBJECTIVE: The study aimed to assess
pelvic pain and quality of life before and after laparoscopic bowel resection for
rectosigmoid endometriosis. DESIGN: The study involved prospectively collected
data regarding pelvic pain and quality of life before and after surgery.
SETTINGS: It was conducted at a tertiary endometriosis referral unit at Aarhus
University Hospital. PATIENTS: A total of 175 women were included. INTERVENTION:
Patients underwent laparoscopic bowel resection for endometriosis. MAIN OUTCOME
MEASURES: Questionnaires for pain (Numerical Rating Scale) and quality of life
(RAND Short Form-36) were answered before and 1 year after surgery. Data on
analgesic and hormone treatment were collected. Preoperative and postoperative
pelvic pain and quality-of-life scores were compared, and risk factors for
improvement/worsening were identified. RESULTS: A total of 97.1% of the women
completed the 1-year follow up. A significant decrease (p = 0.0001) was observed
on all pelvic pain parameters. Most profound was the decrease in dyschezia. A
significant improvement on all quality-of-life scores was observed (p = 0.0001).
A surgical complication did not have a negative impact on outcome 1 year after
surgery. The postoperative outcome was not related to the type of surgery.
LIMITATIONS: This is an observational study without a control group. Risk factor
data should be interpreted with caution, because the study was relatively
underpowered for some of the rare outcomes. CONCLUSIONS: A significant and
clinically relevant improvement in pelvic pain and quality of life 1 year after
laparoscopic bowel resection for endometriosis was found. We strongly recommend
surgery for rectosigmoid endometriosis that is unresponsive to conservative
treatment. See Video Abstract at http://links.lww.com/DCR/A472.
PMID- 29337780
TI - Efficacy and Safety of Sodium Picosulfate/Magnesium Citrate for Bowel Preparation
in a Physically Disabled Outpatient Population: A Randomized, Endoscopist-Blinded
Comparison With Ascorbic Acid-Enriched Polyethylene Glycol Solution Plus
Bisacodyl (The PICO-MOVI Study).
AB - BACKGROUND: Because of its volume, adequate bowel preparation remains problematic
in physically unfit patients. OBJECTIVE: This study aimed to compare a small
volume sodium picosulfate/magnesium citrate preparation with a 2-L ascorbic acid
enriched polyethylene glycol solution plus bisacodyl. DESIGN: This study has a
noninferiority design, assuming that ascorbic acid-enriched polyethylene glycol
solution plus bisacodyl is 70% efficacious in achieving an Ottawa score <=7 and
accepting a difference in success rate of <15% with a target enrollment of 146
patients per group. SETTING: This study was conducted in an outpatient
department. PATIENTS: Patients referred for diagnostic colonoscopy were randomly
assigned. Key exclusion criteria were severe kidney disease, ASA class >=III, and
hospital admission. INTERVENTION: Patients were randomly assigned to receive
sodium picosulfate/magnesium citrate or ascorbic acid-enriched polyethylene
glycol solution plus bisacodyl according to a split-dose regimen. Patients in the
sodium picosulfate/magnesium citrate group received advice on the recommended 4-L
fluid intake. Patients in the ascorbic acid-enriched polyethylene glycol solution
plus bisacodyl group received 2 bisacodyl tablets 2 days before and advice on the
additionally recommended 2-L fluid intake. MAIN OUTCOME MEASURES: To assess bowel
cleansing adequacy, the Ottawa, Aronchick, and Boston scores were used.
Colonoscopy quality measures were obtained. Safety was assessed for a 30-day
follow-up period. RESULTS: Overall, 341 patients (169 men, mean age 57.0 years;
BMI 26.2 kg/m) were included. Comorbidities were present in 76.2% of patients,
and 75.4% of patients used medication. An adequate Ottawa score was obtained in
81.4% and 75.8% of patients receiving ascorbic acid-enriched polyethylene glycol
solution plus bisacodyl and sodium picosulfate/magnesium citrate (difference of
5.6% (95% CI, -3.5 to -14.6; p = 0.023)), showing noninferiority of the sodium
picosulfate/magnesium citrate therapy. Ottawa segmental scores were lower for
sodium picosulfate/magnesium citrate in the right and transverse colon. In both
groups, successful ileocecal intubation was achieved in 95%. No medication
related adverse events were reported. LIMITATIONS: These results in a physically
disabled ambulant population cannot be extrapolated to immobile, hospitalized
patients. CONCLUSIONS: Sodium picosulfate/magnesium citrate proved to be
noninferior to ascorbic acid-enriched polyethylene glycol solution plus bisacodyl
in efficacy and safety. Timing of the colonoscopy and addition of bisacodyl to
sodium picosulfate/magnesium citrate warrants further consideration. See Video
Abstract at http://links.lww.com/DCR/A461.
PMID- 29337781
TI - Comparison of Western and Asian Guidelines Concerning the Management of Colon
Cancer.
AB - BACKGROUND: Guidelines are important to standardize treatments and optimize
outcomes. Several societies have published authoritative guidelines for patients
with colon cancer, and a certain degree of variation can be predicted. OBJECTIVE:
This study aims to compare Western and Asian guidelines for the management of
colon cancer. DATA SOURCES: A literature review was performed following Preferred
Reporting Items for Systematic Reviews and Meta-Analyses guidelines for studies
published between 2010 and 2017 by the online resources from the official Web
sites of the societies/panels. Sources included guidelines by European Society of
Medical Oncology, the Japanese Society for Cancer of the Colon and Rectum, and
the National Comprehensive Cancer Network. STUDY SELECTION: Only full-text
studies and the latest guidelines dealing with colon cancer were included.
Studies and guidelines were separately assessed by 2 authors, who independently
identified discrepancies and areas for further research. These were discussed and
agreed with by all the authors. MAIN OUTCOME MEASURES: The recommendations of the
guidelines of each society were compared, seeking discrepancies and potential
areas for improvement. RESULTS: Endoscopic techniques for the management of early
colon cancer are discussed in detail in the Asian guidelines. Asian guidelines
advocate extended (D3) lymphadenectomy on a routine basis in T3/T4 and in
selected T2 patients, whereas such an approach is still under investigation in
Western countries. Only US guidelines describe neoadjuvant chemotherapy and
radiotherapy. All the guidelines recommend adjuvant treatment in selected stage
II patients, but agreement exists that this is performed without solid evidence,
because better outcomes are hypothesized based on studies including stage III or
stage II/III patients. The role of cytoreductive surgery with intra-abdominal
chemotherapy is dubious, and European guidelines only recommend it in the setting
of trials. Asian guidelines endorse an aggressive surgical approach to peritoneal
disease. Only US guidelines include a patient advocate in the drafting panel.
LIMITATIONS: Bias may have arisen from country-specific socioeconomic and
cultural issues, and from the latest available updates. CONCLUSIONS: Surgical
approaches to colon cancer differ significantly among Western and Asian
guidelines, reflecting different concepts of treatment. The role of adjuvant
treatment in node-negative disease and quality-of-life assessment need further
research.
PMID- 29337782
TI - Laparoscopic Rectovaginopexy for Neorectal Prolapse After Transanal Total
Mesorectal Excision.
PMID- 29337783
TI - S1 Sacrectomy for Re-recurrent Rectal Cancer: Our Experience with Reconstruction
Using an Expandable Vertebral Body Replacement Device.
AB - INTRODUCTION: R0 resection is achieved by high sacrectomy for local recurrence of
colorectal cancer, but significant rates of perioperative complications and long
term patient morbidity are associated with this procedure. In this report, we
outline our unique experience of using an expandable cage for vertebral body
reconstruction following S1 sacrectomy in a 66-year-old patient with re-recurrent
rectal cancer. We aim to highlight several key steps, with a view to improving
postoperative outcomes. TECHNIQUE: A midline laparotomy was performed with the
patient in supine Lloyd-Davies position, demonstrating recurrence of tumor at the
S1 vertebral body. Subtotal vertebral body excision of S1 with sparing of the
posterior wall and ventral foramina was completed by using an ultrasonic bone
aspirator. Reconstruction was performed using an expandable corpectomy spacer
system. The system was assembled and expanded in situ to optimally bridge the
corpectomy. The device was secured into the L5 and S2 vertebrae by means of
angled end plate screws superiorly and inferiorly. Bone grafts were positioned
adjacent to the implant after this. RESULTS: Total operating time was 266 minutes
with 350 mL of intraoperative blood loss. There were no immediate postoperative
complications. The patient did not report any back pain at the time of discharge,
and no neurological deficit was reported or identified. Postoperative CT scan
showed excellent vertebral alignment and preservation of S1 height. CONCLUSION:
We conclude that high sacrectomy with an expandable metal cage is feasible in the
context of re-recurrent rectal cancer when consideration is given to the method
of osteotomy and vertebral body replacement.
PMID- 29337784
TI - The Sharp End of Pilonidal Disease.
PMID- 29337785
TI - Authors Reply.
PMID- 29337786
TI - Mechanical Bowel Preparation Before Colorectal Surgery in Enhanced Recovery
Programs: Discrepancy Between the American and European Guidelines.
PMID- 29337787
TI - Authors Reply.
PMID- 29337790
TI - Can a Multicenter Pneumonia Zero Bundle Reduce Ventilator-Associated Pneumonias?
PMID- 29337789
TI - Multicohort Analysis of Whole-Blood Gene Expression Data Does Not Form a Robust
Diagnostic for Acute Respiratory Distress Syndrome.
AB - OBJECTIVES: To identify a novel, generalizable diagnostic for acute respiratory
distress syndrome using whole-blood gene expression arrays from multiple acute
respiratory distress syndrome cohorts of varying etiologies. DATA SOURCES: We
performed a systematic search for human whole-blood gene expression arrays of
acute respiratory distress syndrome in National Institutes of Health Gene
Expression Omnibus and ArrayExpress. We also included the Glue Grant gene
expression cohorts. STUDY SELECTION: We included investigator-defined acute
respiratory distress syndrome within 48 hours of diagnosis and compared these
with relevant critically ill controls. DATA EXTRACTION: We used multicohort
analysis of gene expression to identify genes significantly associated with acute
respiratory distress syndrome, both with and without adjustment for clinical
severity score. We performed gene ontology enrichment using Database for
Annotation, Visualization and Integrated Discovery and cell type enrichment tests
for both immune cells and pneumocyte gene expression. Finally, we selected a gene
set optimized for diagnostic power across the datasets and used leave-one-dataset
out cross validation to assess robustness of the model. DATA SYNTHESIS: We
identified datasets from three adult cohorts with sepsis, one pediatric cohort
with acute respiratory failure, and two datasets of adult patients with trauma
and burns, for a total of 148 acute respiratory distress syndrome cases and 268
critically ill controls. We identified 30 genes that were significantly
associated with acute respiratory distress syndrome (false discovery rate < 20%
and effect size >1.3), many of which had been previously associated with sepsis.
When metaregression was used to adjust for clinical severity scores, none of
these genes remained significant. Cell type enrichment was notable for bands and
neutrophils, suggesting that the gene expression signature is one of acute
inflammation rather than lung injury per se. Finally, an attempt to develop a
generalizable diagnostic gene set for acute respiratory distress syndrome showed
a mean area under the receiver-operating characteristic curve of only 0.63 on
leave-one-dataset-out cross validation. CONCLUSIONS: The whole-blood gene
expression signature across a wide clinical spectrum of acute respiratory
distress syndrome is likely confounded by systemic inflammation, limiting the
utility of whole-blood gene expression studies for uncovering a generalizable
diagnostic gene signature.
PMID- 29337791
TI - "Judge a Man by His Questions Rather Than by His Answers" Voltaire.
PMID- 29337792
TI - Early Fluid Management in Sepsis: Yes.
PMID- 29337793
TI - Expanding the Reach of Critical Care Pharmacists Globally.
PMID- 29337794
TI - Noninvasive Treatment of Hypoxemic Respiratory Failure: Give It a Try... But Do
Not Push Too Hard.
PMID- 29337795
TI - Renal Decapsulation to Treat Ischemic Acute Kidney Injury: A New Twist in an Old
Tale.
PMID- 29337796
TI - Prolonged Infusions: The Significance of How.
PMID- 29337797
TI - Beta-Lactam Therapeutic Drug Monitoring in the Critically Ill Children: Big
Solution for Infections in Small People?
PMID- 29337798
TI - (Not) Everybody Is Working for the Weekend.
PMID- 29337799
TI - Ventilator Management Guided by Driving Pressure: A Better Way to Protect the
Lungs?
PMID- 29337800
TI - Old Wine in New Bottles: Continuous Versus Intermittent Renal Replacement Therapy
in the ICU.
PMID- 29337801
TI - Informed or Misinformed Consent?
PMID- 29337802
TI - Mesenchymal Stromal Cell Therapy: Does the Source Matter?
PMID- 29337803
TI - From Big Data to Artificial Intelligence: Harnessing Data Routinely Collected in
the Process of Care.
PMID- 29337805
TI - Donation After Cardiocirculatory Determination of Death Requires "Timely" Rather
Than "Early" Referral.
PMID- 29337804
TI - The Association Between Ventilator Dyssynchrony, Delivered Tidal Volume, and
Sedation Using a Novel Automated Ventilator Dyssynchrony Detection Algorithm.
AB - OBJECTIVE: Ventilator dyssynchrony is potentially harmful to patients with or at
risk for the acute respiratory distress syndrome. Automated detection of
ventilator dyssynchrony from ventilator waveforms has been difficult. It is
unclear if certain types of ventilator dyssynchrony deliver large tidal volumes
and whether levels of sedation alter the frequency of ventilator dyssynchrony.
DESIGN: A prospective observational study. SETTING: A university medical ICU.
PATIENTS: Patients with or at risk for acute respiratory distress syndrome.
INTERVENTIONS: Continuous pressure-time, flow-time, and volume-time data were
directly obtained from the ventilator. The level of sedation and the use of
neuromuscular blockade was extracted from the medical record. Machine learning
algorithms that incorporate clinical insight were developed and trained to detect
four previously described and clinically relevant forms of ventilator
dyssynchrony. The association between normalized tidal volume and ventilator
dyssynchrony and the association between sedation and the frequency of ventilator
dyssynchrony were determined. MEASUREMENTS AND MAIN RESULTS: A total of 4.26
million breaths were recorded from 62 ventilated patients. Our algorithm detected
three types of ventilator dyssynchrony with an area under the receiver operator
curve of greater than 0.89. Ventilator dyssynchrony occurred in 34.4% (95% CI,
34.41-34.49%) of breaths. When compared with synchronous breaths, double
triggered and flow-limited breaths were more likely to deliver tidal volumes
greater than 10 mL/kg (40% and 11% compared with 0.2%; p < 0.001 for both
comparisons). Deep sedation reduced but did not eliminate the frequency of all
ventilator dyssynchrony breaths (p < 0.05). Ventilator dyssynchrony was
eliminated with neuromuscular blockade (p < 0.001). CONCLUSION: We developed a
computerized algorithm that accurately detects three types of ventilator
dyssynchrony. Double-triggered and flow-limited breaths are associated with the
frequent delivery of tidal volumes of greater than 10 mL/kg. Although ventilator
dyssynchrony is reduced by deep sedation, potentially deleterious tidal volumes
may still be delivered. However, neuromuscular blockade effectively eliminates
ventilator dyssynchrony.
PMID- 29337806
TI - The authors reply.
PMID- 29337807
TI - Extracorporeal Membrane Oxygenation-Associated Infections: Carefully Consider
Cannula Infections!
PMID- 29337808
TI - The authors reply.
PMID- 29337809
TI - Untargeted Antifungal Treatment in the ICU: Changing Definitions and Labels Do
Not Change the Evidence.
PMID- 29337810
TI - The authors reply.
PMID- 29337811
TI - Individualizing Cerebral Perfusion Pressure Targets.
PMID- 29337812
TI - The authors reply.
PMID- 29337813
TI - Heparin-Free Regional Anticoagulation: There Are Significant Differences Between
Citrate-Containing Dialysate and Regional Citrate Anticoagulation.
PMID- 29337814
TI - The authors reply.
PMID- 29337815
TI - Impact of Moderate Hyperchloremia on Clinical Outcomes in Intracerebral
Hemorrhage Patients. Is There Still Room for Continuous Infusion of 3% Hypertonic
Saline?
PMID- 29337816
TI - The authors reply.
PMID- 29337817
TI - Burnout Research: Eyes Wide Shut.
PMID- 29337818
TI - The authors reply.
PMID- 29337819
TI - Is Oxygenation Really an Intrinsic Predictive Factor of Mortality in Patients
Undergoing Extracorporeal Life Support?
PMID- 29337820
TI - The authors reply.
PMID- 29337821
TI - Systolic Dysfunction Following Traumatic Brain Injury.
PMID- 29337822
TI - The authors reply.
PMID- 29337823
TI - Noninvasive Ventilation in Acute Respiratory Failure: Who Will Benefit?
PMID- 29337824
TI - The authors reply.
PMID- 29337825
TI - Effect of Patient- and Family-Centered Care Interventions on ICU Length of Stay.
PMID- 29337826
TI - The author replies.
PMID- 29337827
TI - Severe Burnout Is Common Among Critical Care Physician Assistants: Retraction.
PMID- 29337828
TI - Semiautomated Subretinal Fluid Injection Method Using Viscous Fluid Injection
Mode.
PMID- 29337829
TI - Estimation of Repetitions to Failure for Monitoring Resistance Exercise
Intensity: Building a Case for Application.
AB - Hackett, DA, Cobley, SP, and Halaki, M. Estimation of repetitions to failure for
monitoring resistance exercise intensity: Building a case for application. J
Strength Cond Res 32(5): 1352-1359, 2018-The purpose of this study was to (a)
examine the accuracy of Estimated Repetitions to Failure (ERF) during resistance
exercise between 2 sessions and (b) compare ERF to rating of perceived exertion
(RPE) for determining proximity to momentary failure. Forty-eight adults with
recreational resistance training experience performed 3 sets of 10 repetitions at
70% one-repetition maximum (1RM) and 80% 1RM for the chest press and leg press,
respectively. At the completion of each set, participants reported their ERF and
then continued repetitions to failure to determine actual repetitions to failure
(ARF). Two sessions of the same experimental protocol were performed with 48
hours between bouts. For session 1, error in ERF was greater during the first
sets compared with third sets for the chest press (2.0 vs. 0.6 repetitions and p
< 0.001) and leg press (3.1 vs. 1.6 repetitions and p < 0.001). No differences
for error in ERF were observed between sessions 1 and 2 for the chest press (p >
0.944); however, less error in ERF was found for the leg press during set 1 of
session 2 (3.1 vs. 1.9 repetitions and p < 0.013). Strong to very strong
relationships were found between ERF and ARF (r = 0.59-0.87 and p < 0.01),
whereas most relationships for RPE and ARF were small to moderate (r = 0.32 to
0.42 and p < 0.01). Improvement in the accuracy of ERF after a single training
bout is minimal, whereas ERF compared with RPE seems to have greater sensitivity
for discriminating momentary failure.
PMID- 29337830
TI - Exploring the effects of playing formations on tactical behaviour and external
workload during football small-sided games.
AB - This study aimed to identify the effects of playing formations on tactical
behaviour and external workload during football small-sided games. Twenty-three
semi-professional footballers integrated three different playing formations in a
7-a-side small-sided game, according to their specific player positions: team
4:3:0 (4 defenders, 3 midfielders); team 4:1:2 (4 defenders, 1 midfielder, 2
forwards); and team 0:4:3 (4 midfielders, 3 forwards). Based on players' movement
trajectories, the following individual and collective tactical variables were
calculated: total distance covered and distance covered while walking, jogging,
running and sprinting, distance from each player to both own and opponent's team
centroid (Dist CG and Dist OPP CG, respectively), individual area, team length,
team width and surface area. Approximate entropy (ApEn) was computed to identify
the regularity of each variable. The team 4:3:0 promoted players' space
exploration with moderate physical efforts. The team 4:1:2 promoted compactness
and regularity of the team with increase in the physical efforts. The team 0:4:3
promoted team balance and adaptability on space coverage with increase in
physical efforts. Concluding, different playing formations support different game
dynamics, and variations on external load were directly linked with the
variations on tactical behaviour. The analysis tactical behaviour through
quantification of variability of patterns of play and quantification of distance
covered at different velocities were the most useful information for the analysis
of the effects of practice task manipulations. Therefore, in a practical sense,
strength and conditioning coaches should plan and monitor these tasks in
interaction with the head coaches.
PMID- 29337831
TI - Acute Effects of a Caffeine-Containing Supplement on Anaerobic Power and
Subjective Measurements of Fatigue in Recreationally Active Men.
AB - Hahn, CJ, Jagim, AR, Camic, CL, and Andre, MJ. Acute effects of a caffeine
containing supplement on anaerobic power and subjective measurements of fatigue
in recreationally active men. J Strength Cond Res 32(4): 1029-1035, 2018-Studies
show mixed results for the effects of caffeine on performance, warranting further
investigation. The purpose of this study was to examine the acute effects of a
caffeine-containing supplement on anaerobic power and subjective measurements of
fatigue during resisted sprinting on men. Fourteen recreationally active men (N =
14; [mean +/- SD], age: 21.0 +/- 0.7 years, height: 178.5 +/- 5.1 cm, body mass:
77.3 +/- 9.6 kg, and percent body fat: 12.6 +/- 4.8%) participated in a double
blind, placebo-controlled, within-subject crossover design study. The first visit
required each participant to complete 3 sets of practice sprints on a
nonmotorized treadmill ranging from 10 to 20 seconds. During the second visit,
participants completed 5 more practice sprints ranging from 15 to 25 seconds.
During the third and fourth visits, participants ingested one serving of a
caffeine-containing or placebo beverage (the opposite beverage was consumed
during the fourth visit), rested for 20 minutes, and completed a dynamic warm-up
before sprinting. Anaerobic power was assessed using a countermovement vertical
jump and nonmotorized treadmill sprint test. Psychological variables were scored
using a 5-point Likert scale. No significant (p <= 0.05) differences were
observed between conditions for average (p = 0.22) or peak power (p = 0.43). Both
conditions resulted in a significant increase in fatigue, although the increase
was less for the caffeine condition (caffeine [INCREMENT] = 0.93 and placebo
[INCREMENT] = 1.71). These findings indicated that the caffeine-containing
supplement improved perceived measures of fatigue but not power indices assessed
through vertical jump or nonmotorized treadmill sprinting. The consumption of a
caffeine beverage may be beneficial for reducing perceived fatigue during acute
anaerobic exercise, particularly when repeated sprints are used.
PMID- 29337832
TI - Comparison of Step-by-Step Kinematics in Repeated 30-m Sprints in Female Soccer
Players.
AB - van den Tillaar, R. Comparison of step-by-step kinematics in repeated 30-m
sprints in female soccer players. J Strength Cond Res 32(7): 1923-1928, 2018-The
aim of this study was to compare kinematics in repeated 30-m sprints in female
soccer players. Seventeen subjects performed seven 30-m sprints every 30 seconds
in one session. Kinematics was measured with an infrared contact mat and laser
gun, and running times with an electronic timing device. The main findings were
that sprint times increased in the repeated-sprint ability test. The main changes
in kinematics during the repeated-sprint ability test were increased contact time
and decreased step frequency, whereas no change in step length was observed. The
step velocity increased in almost each step until the 14th, which occurred around
22 m. After this, the velocity was stable until the last step, when it decreased.
This increase in step velocity was mainly caused by the increased step length and
decreased contact times. It was concluded that the fatigue induced in repeated 30
m sprints in female soccer players resulted in decreased step frequency and
increased contact time. Using this approach in combination with a laser gun and
infrared mat for 30 m makes it very easy to analyze running kinematics in
repeated sprints in training. This extra information gives the athlete, coach,
and sports scientist the opportunity to give more detailed feedback and helps to
target these changes in kinematics better to enhance repeated-sprint performance.
PMID- 29337833
TI - Effects of Plyometric and Resistance Training on Muscle Strength, Explosiveness
and Neuromuscular Function in Young Adolescent Soccer Players.
AB - This study examined the effect of 8-weeks of free-weight-resistance (RT) and
plyometric (PLYO) training on maximal strength, explosiveness and jump
performance compared with no added training (CON), in young male soccer players.
Forty-one 11[FIGURE DASH]13-year-old soccer players were divided into three
groups (RT, PLYO, CON). All participants completed isometric and dynamic (240
degrees /s) knee extensions pre- and post-training. Peak torque (pT), peak rate
of torque development (pRTD), electromechanical-delay (EMD), rate of muscle
activation (Q50), m. vastus-lateralis thickness (VLT), and jump performance were
examined. pT, pRTD and jump performance significantly improved in both training
groups. Training resulted in significant (p<0.05) increases in isometric pT (23.4
vs. 15.8%) and pRTD (15.0 vs. 17.6%), in RT and PLYO, respectively. During
dynamic contractions, training resulted in significant increases in pT (12.4 and
10.8% in RT and PLYO, respectively), but not pRTD. Jump performance increased in
both training groups (RT=10.0%, PLYO=16.2%), with only PLYO significantly
different from CON. Training resulted in significant increases in VLT (RT=6.7%.
PLYO=8.1%). There were no significant EMD changes. In conclusion, 8-week free
weight resistance and plyometric training resulted in significant improvements in
muscle strength and jump performance. Training resulted in similar muscle
hypertrophy in the two training modes, with no clear differences in muscle
performance. Plyometric training was more effective in improving jump
performance, while free-weight resistance training was more advantageous in
improving peak torque, where the stretch reflex was not involved.
PMID- 29337834
TI - Manipulating Field Dimensions During Small-sided Games Impacts the Technical and
Physical Profiles of Australian Footballers.
AB - Brock, F, Christopher, J, Harry, B, and Carl, WT. Manipulating field dimensions
during small-sided games impacts the technical and physical profiles of
Australian footballers. J Strength Cond Res 32(7): 2039-2044, 2018-This study
investigated the effect of manipulating field dimensions on the technical and
physical profiles of Australian football (AF) players during small-sided games
(SSGs). A total of 40 male players (23.9 +/- 3.5 years) participated in 3, five-a
side SSGs; defined as "small" (20 * 30 m; 600 m), "medium" (30 * 40 m; 1,200 m),
and "large" (40 * 50 m; 2,000 m). Notational analyses enabled the quantification
of technical skill indicators, whereas physical activity profiles were measured
using microtechnology, resulting in 18 criterion variables. A multivariate
analysis of variance modeled the main effect of field dimension on the criterion
variables. A significant main effect was observed (V = 1.032; F38, 102 = 2.863; p
<= 0.05), with the "small" and "medium" SSGs generating more turnovers and
ineffective handballs relative to the "large" SSG. Furthermore, the "small" SSG
generated more tackles and fewer bounces compared with the "large" SSG. The
"large" SSG generated a greater absolute distance, relative distance, maximum
velocity, PlayerLoad, and distance >4.16 m.s compared with the "small" and
"medium" SSGs. These results provide AF coaches with insights into how task
constraint manipulation impacts the technical and physical profiles of players
during small-sided game-play. Thus, coaches and physical performance specialists
could use this information to assist with the tactical periodization of technical
complexity and physical load at different phases of the AF season.
PMID- 29337835
TI - Promethazine and Oral Midazolam Preanesthetic Children Medication.
AB - AIMS: Several kinds of drugs have been investigated in preschool children as a
preanesthetic sedation after various routes of administration for surgeries. This
study aims to compare the efficacy of promethazine and oral midazolam for
premedication in children aged 3 to 9 years who were scheduled for surgeries.
METHODS: This is a double-blind randomized controlled study conducted on 93
patients between the age of 3 and 9 years at Loresten University of Medical
Sciences Teaching Hospital, Khoramabad, Iran. The subjects were grouped into P
(promethazine), M (midazolam), and C (control). About 0.3 mg/kg of oral
promethazine was administered to patients in group P, 0.5 mg/kg of oral midazolam
was administered to patients in group M, and 3 mL of normal saline as placebo was
administered to patients in group C. Patient satisfaction, sedation and emotional
score, systolic blood pressure (SBP), diastolic blood pressure, respiratory rate
(RR), and heart rate (HR) were recorded. RESULTS: There was no statistically
significant difference among the 3 groups. However, the period after medication,
it was observed that SBP, diastolic blood pressure, RR, and HR in group C were
statistically significantly higher than those in groups M and P. These 2 groups
are similar in terms of SBP, RR, and HR. The emotional scores were comparable for
the 2 groups. It was between 3.97 +/- 0.6 to 1.7 +/- 0.5 in group M and from 3.45
+/- 1.17 to 2.745 +/- 0.997 in group P in a Kruskal-Wallis test. CONCLUSIONS:
This study shows that both test groups reduce stress at the time of anesthetic
induction and separation from their parents with similar effect. Both of the
anesthetics are easily administered without the necessity of an additional
equipment. A shorter period to maximal sedation for midazolam is an advantage,
thus, making the drug helpful, mostly in the outpatient setting.
PMID- 29337836
TI - Fever as a Presenting Symptom in Children Evaluated for Ileocolic
Intussusception: The Experience of a Large Tertiary Care Pediatric Hospital.
AB - BACKGROUND: Intussusception is the most common cause of intestinal obstruction in
young children, and delayed diagnosis may lead to bowel perforation. The
objective of this study was to determine the prevalence of fever in patients with
ileocolic intussusception and to determine its utility as a predictive symptom.
METHODS: This was a 3-year retrospective study, at a tertiary care center, of
children aged 1 month to 6 years, presenting with possible intussusception.
Charts were reviewed for clinical signs and symptoms at presentation, and all
diagnostic studies were retrieved. A pediatric radiologist reviewed all
ultrasounds. RESULTS: A total of 488 ultrasounds were performed on suspicion of
intussusception. In 30 patients with confirmed ileocolic intussusception, mean
age was 27 months and all were successfully reduced by air enema. Of 118 patients
with fever, 2 had confirmed intussusception, 1 with pneumonia and 1 with acute
otitis media, compared with 116 febrile patients with negative ultrasounds (P <
0.05). CONCLUSIONS: Traditional teaching is that intussusception presents as
intermittent colicky abdominal pain, red currant jelly stool, vomiting, and a
palpable abdominal mass, but it is important to remember that this classic triad
is a very late finding and this condition should be recognized before the
development of these findings. The concurrence of fever can help to rule out the
possibility of intussusception and prompt the health care professional to search
diligently for alternative infectious etiologies but cannot eliminate the
possibility, especially when other findings suggestive of intussusception are
present.
PMID- 29337837
TI - Accidental Rivaroxaban Intoxication in a Boy: Some Lessons in Managing New Oral
Anticoagulants in Children.
AB - Novel oral anticoagulants offer equivalent or improved therapeutic profiles
compared with warfarin, with less risk of bleeding, no interactions with food,
and no need for routine laboratory monitoring. Caution must be exercised in using
these drugs in certain patient populations, for example, renal insufficiency,
those receiving additional antithrombotic therapy, those with questionable
compliance, children, and those with a high risk of gastrointestinal bleeding.
One of the novel oral anticoagulants, rivaroxaban, is a direct Factor Xa
inhibitor, used to reduce risk of stroke and systemic embolism in patients with
nonvalvular atrial fibrillation, deep vein thrombosis, and pulmonary embolism. We
report a child who presented abnormal coagulation tests after unintended
ingestion of 4 tablets of rivaroxaban. The patient was treated with fresh frozen
plasma as well as admitted to intensive care and improved several hours later. We
discuss his presentation and review of the literature on this topic.
PMID- 29337838
TI - Comparison Between Small and Large Bowel Intussusception in Children: The
Experience of a Large Tertiary Care Pediatric Hospital.
AB - BACKGROUND: Intussusception is the most common cause of intestinal obstruction in
young children, and delayed diagnosis may lead to serious sequelae. The objective
of this study was to determine the prevalence of ileoileal intussusception and to
document and compare clinical outcomes with ileocolic intussusception. METHODS: A
retrospective cohort study of children with an abdominal ultrasound that
diagnosed intussusception. Clinical data and diagnostic studies were retrieved,
to compare ileoileal with ileocolic intussusception. RESULTS: A total of 488
patients were evaluated with an abdominal ultrasound on suspicion of
intussusception; 54 (11%) had ileoileal intussusception and 30 (6%) ileocolic
intussusception. The significant features distinguishing the 2 conditions were
fever, more common in patients with ileoileal intussusception, and an abdominal
mass, which was papable more commonly in ileocolic intussusception. None of the
ileoileal intussusception patients required surgical intervention, and all were
discharged without complication. CONCLUSIONS: With recent advances in abdominal
ultrasound, the diagnosis of ileoileal intussusception has become easier than
before. Patients presenting with small bowel intussusception may not need any
immediate intervention. The presence of fever supports the diagnosis of ileoileal
intussusception.
PMID- 29337839
TI - Serum Admission 25-Hydroxyvitamin D Levels and Outcomes in Initially Non-Septic
Critically Ill Patients.
AB - INTRODUCTION: To examine whether very low levels of 25-hydroxyvitamin D {25(OH)D}
upon admission to the intensive care unit (ICU) are associated with worse
outcomes. METHODS: Retrospective observational cohort study of critically ill
patients treated in a multidisciplinary ICU. Two hundred twenty seven initially
non-septic, critically ill patients, in whom 25-hydroxyvitamin D was measured at
ICU admission. An additional group of 192 healthy subjects was also used.
Patients were categorized according to their vitamin D levels at admission; the
two patient groups were those with severely low 25-hydroxyvitamin D levels (<7
ng/mL, N = 101) and those with vitamin D levels >=7 ng/mL, N = 126. RESULTS: ICU
admission 25-hydroxyvitamin D levels of critically ill patients were much lower
than those of healthy subjects (P < 0.0001). The median time to sepsis for the
two patient groups did not differ, nor did the length of ICU stay (days). Both
groups exhibited similar hospital mortality rates. However, among the fraction of
patients who eventually became septic (N = 145), the odds ratio (OR) for
developing respiratory infections in patients with admission vitamin levels < 7
ng/mL compared with patients with admission vitamin D levels >=7 ng/mL was 5.25
{95% confidence interval (CI) 1.5-18.32, P = 0.009}. CONCLUSIONS: Initially non
septic critically ill patients appear to have very low ICU admission 25
hydroxyvitamin D levels. Among critically ill patients, severely low vitamin D
levels (<7 ng/mL) at ICU admission do not predict sepsis development, increased
risk of in-hospital mortality, or longer stay in the ICU. However, these severely
low admission vitamin D levels in patients who will eventually develop sepsis are
associated with development of respiratory tract infections.
PMID- 29337840
TI - Targeted Temperature Management at 33 degrees C or 36 degrees C Produces
Equivalent Neuroprotective Effects in the Middle Cerebral Artery Occlusion Rat
Model of Ischemic Stroke.
AB - Targeted temperature management (TTM, 32 degrees C to 36 degrees C) is one of the
most successful achievements in modern resuscitation medicine. It has become
standard treatment for survivors of sudden cardiac arrest to minimize secondary
brain damage. TTM at 36 degrees C is just as effective as TTM at 33 degrees C and
is actually preferred because it reduces adverse TTM-associated effects. TTM also
likely has direct neuroprotective effects in ischemic brains in danger of stroke.
It remains unclear, however, whether higher temperature TTM is equally effective
in protecting the brain from the effects of stroke. Here, we asked whether TTM at
36 degrees C is as effective as TTM at 33 degrees C in improving outcomes in a
middle cerebral artery occlusion (MCAO) model of ischemic stroke. After dividing
rats randomly into MCAO, MCAO+33 degrees C TTM, MCAO+36 degrees C TTM, and sham
groups, we subjected all of them except for the sham group to MCAO for 3 h (for
the behavioral tests) or 4 h (for all other biochemical analyses). We found TTM
protocols at both 33 degrees C and 36 degrees C to produce comparable reductions
of infarct volumes in the MCAO territory and equally attenuate the extracellular
release of high mobility group box 1 in postischemic brains. Both the TTM
conditions prevent the mRNA induction of a major pro-inflammatory cytokine,
tissue necrosis factor-alpha, in the ischemic penumbra region. Finally, both the
TTM protocols produce similar improvements in neurological outcomes in rats, as
measured by a battery of behavior tests 21 h after the start of reperfusion.
These data acquired in a rat MCAO model suggest TTM at 36 degrees C has excellent
therapeutic potential for improving clinical outcomes for patients with acute
ischemic stroke.
PMID- 29337841
TI - Frequency and Severity of Acute Allergic-Like Reactions to Intravenously
Administered Gadolinium-Based Contrast Media in Children.
AB - OBJECTIVES: The purpose of this study is to determine the frequency and severity
of acute allergic-like reactions to gadolinium-based contrast media (GBCM) in
children before, during, and after the transition from gadopentetate dimeglumine
to gadoterate meglumine as our primary clinical GBCM. MATERIALS AND METHODS:
Institutional review board approval was obtained for this Health Insurance
Portability and Accountability Act-compliant retrospective investigation.
Allergic-like reactions to GBCM in pediatric patients were retrospectively
assessed from January 2009 to January 2017, which included a departmental change
of GBCM from gadopentetate dimeglumine to gadoterate meglumine. Allergic-like
reactions were identified from departmental and hospital databases. The number of
doses of GBCM was obtained from billing data. Allergic-like reaction frequencies
for each GBCM were calculated and compared using the chi-squared test. RESULTS: A
total of 32,365 administrations of GBCM occurred during the study period (327 for
gadofosveset trisodium; 672 for gadoxetate disodium; 12,012 for gadoterate
meglumine; and 19,354 for gadopentetate dimeglumine). Allergic-like reactions
occurred after 21 (0.06%) administrations. Reaction frequencies were not
significantly different among the GBCM (0.3% gadofosveset trisodium; 0%
gadoxetate disodium, 0.06% gadoterate meglumine, 0.08% gadopentetate dimeglumine;
P > 0.05). Ten (47.6%) reactions were mild, 10 (47.6%) were moderate, and 1
(4.8%) was severe. The overall reaction frequency peaked during the 6-month
transition period from gadopentetate dimeglumine to gadoterate meglumine (0.20%),
compared with 0.07% pretransition (P = 0.048) and 0.04% posttransition (P =
0.0095). CONCLUSION: Allergic-like reactions to GBCM in children are rare.
Gadoterate meglumine has a reaction frequency that does not significantly differ
from other GBCMs. During the transition from gadopentetate dimeglumine to
gadoterate meglumine, an increase in the frequency of reported allergic-like
reactions was observed, likely reflective of the Weber effect.
PMID- 29337842
TI - Perioperative Coagulation Management in Liver Transplant Recipients.
AB - We review contemporary coagulation management for patients undergoing liver
transplantation. A better understanding of the complex physiologic changes that
occur in patients with end-stage liver disease has resulted in significant
advances in anesthetic and coagulation management. A group of internationally
recognized experts have critically evaluated current approaches for coagulopathy
detection and management. Strategies for blood component and factor replacement
have been evaluated and recommended therapies proposed. Pharmacologic treatment
and prevention of coagulopathy, management of patients receiving antiplatelet
medications, and the role of transesophageal echocardiography for early detection
and management of thromboses are presented.
PMID- 29337843
TI - Evaluation of a Decision Tree for Efficient Antenatal Red Blood Cell Antibody
Screening.
AB - BACKGROUND: Hemolytic disease of the fetus and newborn due to maternal red blood
cell alloimmunization can have serious consequences. Because early detection
enables careful monitoring of affected pregnancies, programs to routinely screen
all pregnant women have been widely adopted. Due to the low prevalence of
alloimmunization, these require large investments of resources to detect a small
number of cases. METHODS: We conducted a validation study of a decision tree
developed in the Netherlands for determining whether to screen for
alloimmunization. In a Swedish cohort, we compared the performance of that
decision tree to two alternative models that used maternal characteristics,
obstetric history, and transfusion history to identify high-risk women for
screening or low-risk women who might be exempt from screening. The models were
compared for predictive ability and potential reduction in the volume of
screening. RESULTS: The decision tree applied to our study population identified
89% of alloimmunized women with a negative predictive value (NPV) of 99.7% by
screening 62% of the population. To achieve the same NPV, our model exempting low
risk women captured 90% of alloimmunizations by screening 63% of the population.
In contrast, the model identifying high-risk women for screening while
maintaining a similar NPV captured 63% of alloimmunized women by screening 20% of
the population. CONCLUSIONS: We validated that an existing decision tree for
selecting women for maternal screening performed well in our population,
identifying a large proportion of women who became alloimmunized, with a
predictive performance almost identical to that of a more elaborate model.
PMID- 29337844
TI - Melanoma of the Skin in the Danish Cancer Registry and the Danish Melanoma
Database: A Validation Study.
AB - BACKGROUND: The nationwide Danish Cancer Registry and the Danish Melanoma
Database both record data on melanoma for purposes of monitoring, quality
assurance, and research. However, the data quality of the Cancer Registry and the
Melanoma Database has not been formally evaluated. METHODS: We estimated the
positive predictive value (PPV) of melanoma diagnosis for random samples of 200
patients from the Cancer Registry (n = 200) and the Melanoma Database (n = 200)
during 2004-2014, using the Danish Pathology Registry as "gold standard"
reference. We further validated tumor characteristics in the Cancer Registry and
the Melanoma Database. Additionally, we estimated the PPV of in situ melanoma
diagnoses in the Melanoma Database, and the sensitivity of melanoma diagnoses in
2004-2014. RESULTS: The PPVs of melanoma in the Cancer Registry and the Melanoma
Database were 97% (95% CI = 94, 99) and 100%. The sensitivity was 90% in the
Cancer Registry and 77% in the Melanoma Database. The PPV of in situ melanomas in
the Melanoma Database was 97% and the sensitivity was 56%. In the Melanoma
Database, we observed PPVs of ulceration of 75% and Breslow thickness of 96%. The
PPV of histologic subtypes varied between 87% and 100% in the Cancer Registry and
93% and 100% in the Melanoma Database. The PPVs for anatomical localization were
83%-95% in the Cancer Registry and 93%-100% in the Melanoma Database.
CONCLUSIONS: The data quality in both the Cancer Registry and the Melanoma
Database is high, supporting their use in epidemiologic studies.
PMID- 29337845
TI - Statistical Power for Trend-in-trend Design.
PMID- 29337846
TI - 25-Hydroxyvitamin D and Long Menstrual Cycles in a Prospective Cohort Study.
AB - BACKGROUND: Vitamin D insufficiency is associated with subfertility and prolonged
estrus cycles in animals, but humans have not been well studied. METHODS: A
prospective time-to-pregnancy study, Time to Conceive (2010-2015), collected up
to 4 months of daily diary data. Participants were healthy, late reproductive
aged women in North Carolina who were attempting pregnancy. We examined menstrual
cycle length as a continuous variable and in categories: long (35+ days) and
short (<=25 days). Follicular phase length and luteal phase length were
categorized as long (18+ days) or short (<=10 days). We estimated associations
between those lengths and serum 25-hydroxyvitamin D (25[OH]D) using linear mixed
models and marginal models. RESULTS: There were 1,278 menstrual cycles from 446
women of whom 5% were vitamin D deficient (25[OH]D, <20 ng/ml), 69% were between
20 and 39 ng/ml, and 26% were 40 ng/ml or higher. There was a dose-response
association between vitamin D levels and cycle length. Compared with the highest
25(OH)D level (>=40 ng/ml), 25(OH)D deficiency was associated with almost three
times the odds of long cycles (adjusted odds ratio [aOR] = 2.8 [95% confidence
interval (CI) = 1.0, 7.5]). The aOR was 1.9 (1.1, 3.5) for 20 to <30 ng/ml. The
probability of a long follicular phase and the probability of a short luteal
phase both increased with decreasing 25(OH)D. CONCLUSIONS: Lower levels of
25(OH)D are associated with longer follicular phase and an overall longer
menstrual cycle. Our results are consistent with other evidence supporting
vitamin D's role in the reproductive axis, which may have broader implications
for reproductive success.
PMID- 29337847
TI - HIV Care Continuum Disparities Among Black Bisexual Men and the Mediating Effect
of Psychosocial Comorbidities.
AB - INTRODUCTION: Differences across the HIV care continuum between men who have sex
with men and women (MSMW) and men who have sex with men only (MSMO) are emerging
in recent literature but have not been comprehensively documented among black
MSM. Although MSMW have lower HIV prevalence than MSMO, they are more likely to
be HIV-positive unaware and be virally unsuppressed. Explanatory factors for
these differences have not previously been assessed. METHODS: Between 2014 and
2016, we surveyed sexually active black MSM 18 years or older at Black Gay Pride
events in 6 U.S. cities (n = 3881), 1229 of whom either self-reported HIV
positive status or tested HIV-positive onsite. We compared HIV-positive MSMW (n =
196) with HIV-positive MSMO (n = 1033) by HIV-positive unaware status, HIV care
uptake, and viral load suppression. We conducted multivariable logistic
regressions and built a structural equation model assessing mediating effects of
psychosocial comorbidities (violence victimization, depression, and polydrug use)
on the relationship between MSMW status and unsuppressed virus. RESULTS: MSMW
were more likely than MSMO to be HIV-positive unaware [adjusted odds ratio (aOR)
= 2.17; 95% confidence interval (CI): 1.58 to 3.00]. Among those who were HIV
positive aware (n = 720), MSMW were more likely to report never receiving HIV
care (aOR = 2.74; 95% CI: 1.05 to 7.16) and to report detectable viral loads (aOR
= 2.34; 95% CI: 1.31 to 4.19). Psychosocial comorbidities significantly mediated
(P = 0.01) the relationship between MSMW status and unsuppressed virus.
DISCUSSION: Black MSMW were less likely than black MSMO to uptake biomedical care
and secondary prevention. Biobehavioral intervention development specific to HIV
positive black MSMW will be most successful if psychosocial comorbidities are
also addressed.
PMID- 29337848
TI - Transmission Networks of HCV Genotype 1a Enriched With Pre-existing Polymorphism
Q80K Among HIV-Infected Patients With Acute Hepatitis C in Poland.
AB - BACKGROUND: Hepatitis C virus (HCV) resistance-associated variants (RAVs) have
been shown to adversely affect treatment response of direct-acting antivirals.
Identifying pre-existing RAVs and transmission networks among HIV/HCV genotype 1
(G1)-infected patients from Poland will assist in shaping surveillance strategies
for HCV. METHODS: NS3 and NS5A sequences were obtained from samples of 112 direct
acting antiviral-naive G1 patients (45 G1a and 67 G1b), of which 74 were
chronically infected and 38 were diagnosed with acute hepatitis C (AHC). RAVs
were identified using geno2pheno, and 98 concatenated NS3/NS5A alignments were
constructed to identify transmission clusters using a maximum likelihood
approach. RESULTS: G1a was notably more prevalent compared with G1b among men
having-sex-with-men (MSM) (60.0% vs. 31.3%, P = 0.004), AHC cases (46.7% vs.
25.4%, P = 0.019), and patients diagnosed with syphilis (52.2% vs. 24.5%, P =
0.009). The overall NS3/NS5A RAVs frequency was 14.3% with variants occurring
more often in G1a compared with G1b (27.5% vs. 5.2%, P = 0.005), mostly for NS3
due to the high prevalence of polymorphism Q80K. NS5A RAVs were only found in
2.9% of sequences. Significant clustering was observed for 73.5% of the Polish
sequences, however, more common in G1a MSM compared with G1b (50.0% vs. 25.9%, P
= 0.02). The identified clusters contained sequences originating from up to 5
Polish cities, located within a mean distance of 370 km. CONCLUSIONS: Close
clustering of Polish strains suggests the presence of compartmentalized epidemics
of MSM that fuel the spread of G1a variants. Particularly patients with AHC form
a national transmission network, including clusters enriched with the NS3 Q80K
polymorphism.
PMID- 29337849
TI - Vitamin E as a Treatment for Nonalcoholic Fatty Liver Disease: Reality or Myth?
AB - Obesity is one of the major epidemics of this millennium, and its incidence is
growing worldwide. Following the epidemics of obesity, nonalcoholic fatty liver
disease (NAFLD) has become a disease of increasing prevalence and a leading cause
of morbidity and mortality closely related to cardiovascular disease,
malignancies, and cirrhosis. It is believed that oxidative stress is a main
player in the development and progression of NAFLD. Currently, a pharmacological
approach has become necessary in NAFLD because of a failure to modify lifestyle
and dietary habits in most patients. Vitamin E is a potent antioxidant that has
been shown to reduce oxidative stress in NAFLD. This review summarizes the
biological activities of vitamin E, with a primary focus on its therapeutic
efficacy in NAFLD.
PMID- 29337850
TI - Rosuvastatin Improves Vaspin Serum Levels in Obese Patients with Acute Coronary
Syndrome.
AB - : Adipose tissue-derived serine protease inhibitor (vaspin), which has endocrine
and local roles in atherosclerosis growth, is also synthesized by adipose tissue;
it was found that vaspin was negatively correlated with blood pressure in obese
patients, while vaspin levels were decreased in endothelial dysfunction. The aim
of the present study was to determine rosuvastatin modulation effects on serum
vaspin levels in acute coronary syndrome (ACS) with class I obesity. A total
number of seventy patients with acute coronary syndrome previously and currently
treated with rosuvastatin was compared to 40 patients with IHD not treated by
rosuvastatin as a control. Vaspin serum levels were higher in rosuvastatin
treated patients with acute coronary syndrome compared to the patients with acute
coronary syndrome not treated by rosuvastatin, p < 0.01. Additionally, in the
rosuvastatin-treated group, patients with STEMI showed higher vaspin serum levels
compared to NSTEMI p < 0.01. CONCLUSION: Rosuvastatin significantly increases
vaspin serum levels in acute coronary syndrome.
PMID- 29337851
TI - Transcriptional Regulation by CpG Sites Methylation in the Core Promoter Region
of the Bovine SIX1 Gene: Roles of Histone H4 and E2F2.
AB - DNA methylation is a major epigenetic modification of the genome and has an
essential role in muscle development. The SIX1 gene is thought to play a
principal role in mediating skeletal muscle development. In the present study, we
determined that bovine SIX1 expression levels were significantly higher in the
fetal bovine group (FB) and in undifferentiated Qinchuan cattle muscle cells
(QCMCs) than in the adult bovine group (AB) and in differentiated QCMCs.
Moreover, a bisulfite sequencing polymerase chain reaction (BSP) analysis of DNA
methylation levels showed that three CpG sites in the core promoter region (-216/
28) of the bovine SIX1 gene exhibited significantly higher DNA methylation levels
in the AB and differentiated QCMCs groups. In addition, we found that DNA
methylation of SIX1 core promoter in vitro obviously influences the promoter
activities. An electrophoretic mobility shift assay (EMSA) and chromatin
immunoprecipitation (ChIP) assay, in combination with site-directed mutation and
siRNA interference, demonstrated that histone H4 and E2F2 bind to the -216/-28
region and play important roles in SIX1 methylation regulation during
development. The results of this study provide the foundation for a better
understanding of the regulation of bovine SIX1 expression via methylation and
muscle developmental in beef cattle.
PMID- 29337852
TI - Reference Gene Selection for Quantitative Real-Time Reverse-Transcriptase PCR in
Annual Ryegrass (Lolium multiflorum) Subjected to Various Abiotic Stresses.
AB - To select the most stable reference genes in annual ryegrass (Lolium
multiflorum), we studied annual ryegrass leaf tissues exposed to various abiotic
stresses by qRT-PCR and selected 11 candidate reference genes, i.e., 18S rRNA,
E2, GAPDH, eIF4A, HIS3, SAMDC, TBP-1, Unigene71, Unigene77, Unigene755, and
Unigene14912. We then used GeNorm, NormFinder, and BestKeeper to analyze the
expression stability of these 11 genes, and used RefFinder to comprehensively
rank genes according to stability. Under different stress conditions, the most
suitable reference genes for studies of leaf tissues of annual ryegrass were
different. The expression of the eIF4A gene was the most stable under drought
stress. Under saline-alkali stress, Unigene14912 has the highest expression
stability. Under acidic aluminum stress, SAMDC expression stability was highest.
Under heavy metal stress, Unigene71 expression had the highest stability.
According to the software analyses, Unigene14912, HIS3, and eIF4A were the most
suitable for analyses of abiotic stress in tissues of annual ryegrass. GAPDH was
the least suitable reference gene. In conclusion, selecting appropriate reference
genes under abiotic stress not only improves the accuracy of annual ryegrass gene
expression analyses, but also provides a theoretical reference for the
development of reference genes in plants of the genus Lolium.
PMID- 29337853
TI - Specific Molecular Signatures for Type II Crustins in Penaeid Shrimp Uncovered by
the Identification of Crustin-Like Antimicrobial Peptides in Litopenaeus
vannamei.
AB - Crustins form a large family of antimicrobial peptides (AMPs) in crustaceans
composed of four sub-groups (Types I-IV). Type II crustins (Type IIa or
"Crustins" and Type IIb or "Crustin-like") possess a typical hydrophobic N
terminal region and are by far the most representative sub-group found in penaeid
shrimp. To gain insight into the molecular diversity of Type II crustins in
penaeids, we identified and characterized a Type IIb crustin in Litopenaeus
vannamei (Crustin-like Lv) and compared Type II crustins at both molecular and
transcriptional levels. Although L. vannamei Type II crustins (Crustin Lv and
Crustin-like Lv) are encoded by separate genes, they showed a similar tissue
distribution (hemocytes and gills) and transcriptional response to the shrimp
pathogens Vibrio harveyi and White spot syndrome virus (WSSV). As Crustin Lv,
Crustin-like Lv transcripts were found to be present early in development,
suggesting a maternal contribution to shrimp progeny. Altogether, our in silico
and transcriptional data allowed to conclude that (1) each sub-type displays a
specific amino acid signature at the C-terminal end holding both the cysteine
rich region and the whey acidic protein (WAP) domain, and that (2) shrimp Type II
crustins evolved from a common ancestral gene that conserved a similar pattern of
transcriptional regulation.
PMID- 29337854
TI - Announcing the 2018 Medicines Travel Award for PostDocs.
AB - For the Medicines Travel Award 2018, we received a total of 41 applications from
all over the world, of a wery high quality[...].
PMID- 29337856
TI - Interaction between Hepatitis B Virus and Toll-Like Receptors: Current Status and
Potential Therapeutic Use for Chronic Hepatitis B.
AB - Immune defense against infection with the hepatitis B virus (HBV) is complex and
involves both host innate and adaptive immune systems. It is well accepted that
the development of sufficient HBV-specific T cell and B cell responses are
required for controlling an HBV infection. However, the contribution of innate
immunity to removing HBV has been explored in recent years. Toll-like receptors
(TLRs) are recognized as the first line of antiviral immunity because they
initiate intracellular signaling pathways to induce antiviral mediators such as
interferons (IFNs) and other cytokines. Recent studies show that the activation
of TLR-mediated signaling pathways results in a suppression of HBV replication in
vitro and in vivo. However, HBV has also evolved strategies to counter TLR
responses including the suppression of TLR expression and the blockage of
downstream signaling pathways. Antiviral treatment in chronic HBV-infected
patients leads to an upregulation of TLR expression and the restoration of its
innate antiviral functions. Thus, TLR activation may serve as an additional
immunotherapeutic option for treating chronic HBV infection in combination with
antiviral treatment.
PMID- 29337858
TI - Investigation on the Effect of a Pre-Center Drill Hole and Tool Material on
Thrust Force, Surface Roughness, and Cylindricity in the Drilling of Al7075.
AB - Drilling is one of the most useful metal cutting processes and is used in various
applications, such as aerospace, electronics, and automotive. In traditional
drilling methods, the thrust force, torque, tolerance, and tribology (surface
roughness) are related to the cutting condition and tool geometry. In this paper,
the effects of a pre-center drill hole, tool material, and drilling strategy
(including continuous and non-continuous feed) on thrust force, surface
roughness, and dimensional accuracy (cylindricity) have been investigated. The
results show that using pre-center drill holes leads to a reduction of the
engagement force and an improvement in the surface quality and cylindricity. Non
continuous drilling reduces the average thrust force and cylindricity value, and
High Speed Steels HSS-Mo (high steel speed + 5-8% Mo) reduces the maximum
quantity of cutting forces. Moreover, cylindricity is directly related to cutting
temperature and is improved by using a non-continuous drilling strategy.
PMID- 29337857
TI - Low Molecular Weight Chitosan-Insulin Complexes Solubilized in a Mixture of Self
Assembled Labrosol and Plurol Oleaque and Their Glucose Reduction Activity in
Rats.
AB - Oral insulin delivery that better mimics physiological pathways is a necessity as
it ensures patient comfort and compliance. A system which is based on a vehicle
of nano order where positively charged chitosan interacts with negatively charged
insulin and forms a polyelectrolyte complex (PEC) solubilizate, which is then
solubilized into an oily phase of oleic acid, labrasol, and plurol oleaque
protects insulin against enzymatic gastrointestinal reduction. The use of an
anionic fatty acid in the oily phase, such as oleic acid, is thought to allow an
interaction with cationic chitosan, hence reducing particle size. Formulations
were assessed based on their hypoglycaemic capacities in diabetic rats as
compared to conventional subcutaneous dosage forms. 50 IU/kg oral insulin
strength could only induce blood glucose reduction equivalent to that of 5 IU/kg
(1 International unit = 0.0347 mg of human insulin). Parameters that influence
the pharmacological availability were evaluated. A preliminary investigation of
the mechanism of absorption suggests the involvement of the lymphatic route.
PMID- 29337859
TI - Effects of Pharmacists' Interventions on Inappropriate Drug Use and Drug-Related
Readmissions in People with Dementia-A Secondary Analysis of a Randomized
Controlled Trial.
AB - Age-associated physiological changes and extensive drug treatment including use
of potentially inappropriate medications (PIMs) pose a significant risk of drug
drug interactions and adverse drug events among elderly people with dementia.
This study aimed at analysing the effects of clinical pharmacists' interventions
on use of PIMs, risk of emergency department visits, and time to
institutionalization. Furthermore, a descriptive analysis was conducted of
circumstances associated with drug-related readmissions. This is a secondary
analysis of data from a randomized controlled intervention study conducted in two
hospitals in Northern Sweden. The study included patients (n = 460) 65 years or
older with dementia or cognitive impairment. The intervention consisted of
comprehensive medication reviews conducted by clinical pharmacists as part of a
healthcare team. There was a larger decrease in PIMs in the intervention group
compared with the control group (p = 0.011). No significant difference was found
in time to first all-cause emergency department visits (HR = 0.994, 95% CI =
0.755-1.307 p = 0.963, simple Cox regression) or time to institutionalization (HR
= 0.761, 95% CI = 0.409-1.416 p = 0.389, simple Cox regression) within 180 days.
Common reasons for drug-related readmissions were negative effects of sedatives,
opioids, antidepressants, and anticholinergic agents, resulting in confusion,
falling, and sedation. Drug-related readmissions were associated with living at
home, heart failure, and diabetes. Pharmacist-provided interventions were able to
reduce PIMs among elderly people with dementia and cognitive impairment.
PMID- 29337860
TI - Reporting and Handling of Indeterminate Bone Scan Results in the Staging of
Prostate Cancer: A Systematic Review.
AB - Bone scintigraphy is key in imaging skeletal metastases in newly diagnosed
prostate cancer. Unfortunately, a notable proportion of scans are not readily
classified as positive or negative but deemed indeterminate. The extent of
reporting of indeterminate bone scans and how such scans are handled in clinical
trials are not known. A systematic review was conducted using electronic
databases up to October 2016. The main outcome of interest was the reporting of
indeterminate bone scans, analyses of how such scans were managed, and
exploratory analyses of the association of study characteristics and the
reporting of indeterminate bone scan results. Seventy-four eligible clinical
trials were identified. The trials were mostly retrospective (85%), observational
(95%), large trials (median 195 patients) from five continents published over
four decades. The majority of studies had university affiliation (72%), and an
author with imaging background (685). Forty-five studies (61%) reported an
indeterminate option for the bone scan and 23 studies reported the proportion of
indeterminate scans (median 11.4%). Most trials (44/45, 98%) reported how to
handle indeterminate scans. Most trials (n = 39) used add-on supplementary
imaging, follow-up bone scans, or both. Exploratory analyses showed a significant
association of reporting of indeterminate results and number of patients in the
study (p = 0.024) but failed to reach statistical significance with other
variables tested. Indeterminate bone scan for staging of prostate cancer was
insufficiently reported in clinical trials. In the case of indeterminate scans,
most studies provided adequate measures to obtain the final status of the
patients.
PMID- 29337861
TI - Protein from Meat or Vegetable Sources in Meals Matched for Fiber Content has
Similar Effects on Subjective Appetite Sensations and Energy Intake-A Randomized
Acute Cross-Over Meal Test Study.
AB - Higher-protein meals decrease hunger and increase satiety compared to lower
protein meals. However, no consensus exists about the different effects of animal
and vegetable proteins on appetite. We investigated how a meal based on vegetable
protein (fava beans/split peas) affected ad libitum energy intake and appetite
sensations, compared to macronutrient-balanced, iso-caloric meals based on animal
protein (veal/pork or eggs). Thirty-five healthy men were enrolled in this acute
cross-over study. On each test day, participants were presented with one of four
test meals (~3550 kilojoules (kJ) 19% of energy from protein), based on fava
beans/split peas (28.5 g fiber), pork/veal or eggs supplemented with pea fiber to
control for fiber content (28.5 g fiber), or eggs without supplementation of
fiber (6.0 g fiber). Subjective appetite sensations were recorded at baseline and
every half hour until the ad libitum meal three hours later. There were no
differences in ad libitum energy intake across test meals (p > 0.05). Further, no
differences were found across meals for hunger, satiety, fullness, prospective
food consumption, or composite appetite score (all p > 0.05). Iso-caloric,
macronutrient-balanced, fiber-matched meals based on vegetable protein (fava
beans/split peas) or animal protein (veal/pork or eggs) had similar effects on ad
libitum energy intake and appetite sensations.
PMID- 29337862
TI - Therapeutic Management of Pseudomonas aeruginosa Bloodstream Infection Non
Susceptible to Carbapenems but Susceptible to "Old" Cephalosporins and/or to
Penicillins.
AB - It is unknown as to whether other beta-lactams can be used for bloodstream
infections (BSI) resulting from Pseudomonas aeruginosa (PA) which are non
susceptible to one or more carbapenem. We conducted a retrospective cohort study
at the Assaf Harofeh Medical Center (AHMC) from January 2010 to August 2014.
Adult patients with PA-BSI non-susceptible to a group 2 carbapenem but
susceptible to ceftazidime or piperacillin (with or without tazobactam), were
enrolled. We compared the outcomes of patients who received an appropriate beta
lactam antibiotic ("cases") to those who received an appropriate non-beta-lactam
antibiotic ("controls"). Whole genome sequencing was performed for one of the
isolates. Twenty-six patients with PA-BSI met inclusion criteria: 18 received a
beta-lactam and 8 a non-beta-lactam (three a fluoroquinolone, two colistin, one a
fluoroquinolone and an aminoglycoside, one a fluoroquinolone and colistin, and
one colistin and an aminoglycoside). All clinical outcomes were similar between
the groups. There were large variations in the phenotypic susceptibilities of the
strains. A detailed molecular investigation of one isolate revealed a strain that
belonged to MLST-137, with the presence of multiple efflux pumps, OXA-50, and a
chromosomally mediated Pseudomonas-derived cephalosporinase (PDC). The oprD gene
was intact. Non-carbapenem-beta-lactams may still be effective alternatives for
short duration therapy (up to 14 days) for BSI caused by a carbapenem non
susceptible (but susceptible to ceftazidime, piperacillin, and/or piperacillin
tazobactam) PA strain. This observation requires further confirmatory analyses.
Future molecular investigations should be performed, in order to further analyze
additional potential mechanisms for this prevalent phenotype.
PMID- 29337864
TI - Effects of Chitosan-PVA and Cu Nanoparticles on the Growth and Antioxidant
Capacity of Tomato under Saline Stress.
AB - Chitosan is a natural polymer, which has been used in agriculture to stimulate
crop growth. Furthermore, it has been used for the encapsulation of nanoparticles
in order to obtain controlled release. In this work, the effect of chitosan-PVA
and Cu nanoparticles (Cu NPs) absorbed on chitosan-PVA on growth, antioxidant
capacity, mineral content, and saline stress in tomato plants was evaluated. The
results show that treatments with chitosan-PVA increased tomato growth.
Furthermore, chitosan-PVA increased the content of chlorophylls a and b, total
chlorophylls, carotenoids, and superoxide dismutase. When chitosan-PVA was mixed
with Cu NPs, the mechanism of enzymatic defense of tomato plants was activated.
The chitosan-PVA and chitosan-PVA + Cu NPs increased the content of vitamin C and
lycopene, respectively. The application of chitosan-PVA and Cu NPs might induce
mechanisms of tolerance to salinity.
PMID- 29337863
TI - Dairy-Related Dietary Patterns, Dietary Calcium, Body Weight and Composition: A
Study of Obesity in Polish Mothers and Daughters, the MODAF Project.
AB - The role of the family environment in regards to dairy products and dietary
calcium in the context of obesity is not fully understood. The aim of the study
was to investigate the association among dairy-related dietary patterns (DDPs),
dietary calcium, body weight and composition in mothers and daughters. Data were
collected through a cross-sectional survey within the MODAF Project. A total
sample of 712 pairs of mothers (<60 years) and daughters (12-21 years) was
studied. This study included 691 pairs. A semi-quantitative food frequency
questionnaire (ADOS-Ca) was used to collect dietary data. Waist circumference
(WC), body fat, waist-to-height ratio (WHtR) and body mass index (BMI) were
determined. Previously derived DDPs were used-three in mothers and three in
daughters. In mothers, two of the DDPs were characterized by higher consumption
of various dairy products with suboptimal calcium content (means: 703 or 796
mg/day) which decreased the chance of: z-WC > 1 standard deviation (SD), WC > 80
cm, body fat > 32%, WHtR > 0.5, BMI = 25-29.9 kg/m2 or BMI >= 30 kg/m2 by 44-67%
when compared to low-dairy low-calcium DDP (288 mg/day). In mothers per 100
mg/day of dietary calcium, the chance of z-WC > 1SD, WC > 80 cm, z-WHtR > 1SD,
WHtR > 0.5 cm, BMI = 25 to 29.9 kg/m2 or BMI >= 30 kg/m2 decreased by 5-9%. In
correspondence analysis, a clear association was found between mothers' and
daughters' low-dairy low-calcium DDPs and upper categories of z-WC (>1 SDs). This
study reinforces evidence of the similarity between mothers and daughters in
dairy-related dietary patterns and provides a new insight on the adverse relation
between low-dairy low-calcium dietary patterns and obesity. It was found that
diets containing various dairy products with suboptimal dietary calcium content
may be recommended in obesity prevention.
PMID- 29337865
TI - Pharmacokinetics and Drug Metabolism in Canada: The Current Landscape-A Summary
of This Indispensable Special Issue.
AB - Canadian Pharmaceutical Scientists have a rich history of groundbreaking research
in pharmacokinetics and drug metabolism undertaken primarily throughout its
Pharmacy Faculties and within the Pharmaceutical and Biotechnology
industry.[...].
PMID- 29337867
TI - Tensile and Creep Testing of Sanicro 25 Using Miniature Specimens.
AB - Tensile and creep properties of new austenitic steel Sanicro 25 at room
temperature and operating temperature 700 degrees C were investigated by testing
on miniature specimens. The results were correlated with testing on conventional
specimens. Very good agreement of results was obtained, namely in yield and
ultimate strength, as well as short-term creep properties. Although the creep
rupture time was found to be systematically shorter and creep ductility lower in
the miniature test, the minimum creep rates were comparable. The analysis of the
fracture surfaces revealed similar ductile fracture morphology for both specimen
geometries. One exception was found in a small area near the miniature specimen
edge that was cut by electro discharge machining, where an influence of the steel
fracture behavior at elevated temperature was identified.
PMID- 29337868
TI - Bacteriophage GC1, a Novel Tectivirus Infecting Gluconobacter Cerinus, an Acetic
Acid Bacterium Associated with Wine-Making.
AB - The Gluconobacter phage GC1 is a novel member of the Tectiviridae family isolated
from a juice sample collected during dry white wine making. The bacteriophage
infects Gluconobacter cerinus, an acetic acid bacterium which represents a
spoilage microorganism during wine making, mainly because it is able to produce
ethyl alcohol and transform it into acetic acid. Transmission electron microscopy
revealed tail-less icosahedral particles with a diameter of ~78 nm. The linear
double-stranded DNA genome of GC1 (16,523 base pairs) contains terminal inverted
repeats and carries 36 open reading frames, only a handful of which could be
functionally annotated. These encode for the key proteins involved in DNA
replication (protein-primed family B DNA polymerase) as well as in virion
structure and assembly (major capsid protein, genome packaging ATPase (adenosine
triphosphatase) and several minor capsid proteins). GC1 is the first tectivirus
infecting an alphaproteobacterial host and is thus far the only temperate
tectivirus of gram-negative bacteria. Based on distinctive sequence and life
style features, we propose that GC1 represents a new genus within the
Tectiviridae, which we tentatively named "Gammatectivirus". Furthermore, GC1
helps to bridge the gap in the sequence space between alphatectiviruses and
betatectiviruses.
PMID- 29337866
TI - CRISPR-Cas Targeting of Host Genes as an Antiviral Strategy.
AB - Currently, a new gene editing tool-the Clustered Regularly Interspaced Short
Palindromic Repeats (CRISPR) associated (Cas) system-is becoming a promising
approach for genetic manipulation at the genomic level. This simple method,
originating from the adaptive immune defense system in prokaryotes, has been
developed and applied to antiviral research in humans. Based on the
characteristics of virus-host interactions and the basic rules of nucleic acid
cleavage or gene activation of the CRISPR-Cas system, it can be used to target
both the virus genome and host factors to clear viral reservoirs and prohibit
virus infection or replication. Here, we summarize recent progress of the CRISPR
Cas technology in editing host genes as an antiviral strategy.
PMID- 29337869
TI - Aquaporin Expression and Water Transport Pathways inside Leaves Are Affected by
Nitrogen Supply through Transpiration in Rice Plants.
AB - The photosynthetic rate increases under high-N supply, resulting in a large CO2
transport conductance in mesophyll cells. It is less known that water movement is
affected by nitrogen supply in leaves. This study investigated whether the
expression of aquaporin and water transport were affected by low-N (0.7 mM) and
high-N (7 mM) concentrations in the hydroponic culture of four rice varieties:
(1) Shanyou 63 (SY63), a hybrid variant of the indica species; (2) Yangdao 6
(YD6), a variant of indica species; (3) Zhendao 11 (ZD11), a hybrid variant of
japonica species; and (4) Jiuyou 418 (JY418), another hybrid of the japonica
species. Both the photosynthetic and transpiration rate were increased by the
high-N supply in the four varieties. The expressions of aquaporins, plasma
membrane intrinsic proteins (PIPs), and tonoplast membrane intrinsic protein
(TIP) were higher in high-N than low-N leaves, except in SY63. Leaf hydraulic
conductance (Kleaf) was lower in high-N than low-N leaves in SY63, while Kleaf
increased under high-N supply in the YD6 variant. Negative correlations were
observed between the expression of aquaporin and the transpiration rate in
different varieties. Moreover, there was a significant negative correlation
between transpiration rate and intercellular air space. In conclusion, the change
in expression of aquaporins could affect Kleaf and transpiration. A feedback
effect of transpiration would regulate aquaporin expression. The present results
imply a coordination of gas exchange with leaf hydraulic conductance.
PMID- 29337870
TI - Glioblastoma under Siege: An Overview of Current Therapeutic Strategies.
AB - Glioblastoma is known to be one of the most lethal and untreatable human tumors.
Surgery and radiotherapy in combination with classical alkylating agents such as
temozolomide offer little hope to escape a poor prognosis. For these reasons,
enormous efforts are currently devoted to refine in vivo and in vitro models with
the specific goal of finding new molecular aberrant pathways, suitable to be
targeted by a variety of therapeutic approaches, including novel pharmaceutical
formulations and immunotherapy strategies. In this review, we will first discuss
current molecular classification based on genomic and transcriptomic criteria.
Also, the state of the art in current clinical practice for glioblastoma therapy
in the light of the recent molecular classification, together with ongoing phases
II and III clinical trials, will be described. Finally, new pharmaceutical
formulations such as nanoparticles and viral vectors, together with new
strategies entailing the use of monoclonal antibodies, vaccines and immunotherapy
agents, such as checkpoint inhibitors, will also be discussed.
PMID- 29337871
TI - Influence of Kartogenin on Chondrogenic Differentiation of Human Bone Marrow
Derived MSCs in 2D Culture and in Co-Cultivation with OA Osteochondral Explant.
AB - Articular cartilage has limited capacity for natural regeneration and repair. In
the present study, we evaluated kartogenin (KGN), a bioactive small heterocyclic
molecule, for its effect on in vitro proliferation and chondrogenic
differentiation of human bone marrow-derived mesenchymal stromal cells (hBMSCs)
in monolayer culture and in co-culture models in vitro. OA osteochondral
cylinders and hBMSCs were collected during total knee replacement. The effect of
KGN on hBMSCs during 21 days of culture was monitored by real-time proliferation
assay, immunofluorescence staining, histological assay, scanning electron
microscopy (SEM) (imaging and multiplex enzyme-linked immunosorbent assay) ELISA
assay. The rate of proliferation of hBMSCs was significantly increased by
treatment with 10 uM KGN during nine days of culture. Histological and SEM
analyses showed the ability of hBMSCs in the presence of KGN to colonize the
surface of OA cartilage and to produce glycosaminoglycans and proteoglycans after
21 days of co-culture. KGN treated hBMSCs secreted higher concentrations of TIMPs
and the secretion of pro-inflammatory molecules (MMP 13, TNF-alpha) were
significantly suppressed in comparison with control without hBMSCs. Our
preliminary results support the concept that 10 uM KGN enhances proliferation and
chondrogenic differentiation of hBMSCs and suggest that KGN is a potential
promoter for cell-based therapeutic application for cartilage regeneration.
PMID- 29337872
TI - Mutation Analysis in Cultured Cells of Transgenic Rodents.
AB - To comply with guiding principles for the ethical use of animals for experimental
research, the field of mutation research has witnessed a shift of interest from
large-scale in vivo animal experiments to small-sized in vitro studies. Mutation
assays in cultured cells of transgenic rodents constitute, in many ways, viable
alternatives to in vivo mutagenicity experiments in the corresponding animals. A
variety of transgenic rodent cell culture models and mutation detection systems
have been developed for mutagenicity testing of carcinogens. Of these, transgenic
Big Blue(r) (Stratagene Corp., La Jolla, CA, USA, acquired by Agilent
Technologies Inc., Santa Clara, CA, USA, BioReliance/Sigma-Aldrich Corp.,
Darmstadt, Germany) mouse embryonic fibroblasts and the lambda Select cII
Mutation Detection System have been used by many research groups to investigate
the mutagenic effects of a wide range of chemical and/or physical carcinogens.
Here, we review techniques and principles involved in preparation and culturing
of Big Blue(r) mouse embryonic fibroblasts, treatment in vitro with
chemical/physical agent(s) of interest, determination of the cII mutant frequency
by the lambda Select cII assay and establishment of the mutation spectrum by DNA
sequencing. We describe various approaches for data analysis and interpretation
of the results. Furthermore, we highlight representative studies in which the Big
Blue(r) mouse cell culture model and the lambda Select cII assay have been used
for mutagenicity testing of diverse carcinogens. We delineate the advantages of
this approach and discuss its limitations, while underscoring auxiliary methods,
where applicable.
PMID- 29337873
TI - Two Novel Proline-Containing Catechin Glucoside from Water-Soluble Extract of
Codonopsis pilosula.
AB - Choushenflavonoids A (1) and B (2), two unusual proline-containing catechin
glucosides, were isolated from the roots of Codonopsis pilosula cultivated in a
high-altitude location of Yunnan province. Their structures were determined by
spectroscopic data and chemical methods. Specifically, the absolute configuration
of glucose residue in 1 and 2 was assigned by acid hydrolysis followed by
derivatization and gas chromatography (GC) analysis. In addition, biological
evaluation of 1 and 2 against Sirtuin 1 (SIRT1) was carried out.
PMID- 29337874
TI - Angular Molecular-Electronic Sensor with Negative Magnetohydrodynamic Feedback.
AB - A high-precision angular accelerometer based on molecular-electronic transfer
(MET) technology with a high dynamic range and a low level of self-noise has been
developed. Its difference from the analogues is in the use of liquid
(electrolyte) as the inertial mass and the use of negative feedback based on the
magnetohydrodynamic effect. This article reports on the development of the
angular molecular-electronic accelerometer with a magnetohydrodynamic cell for
the creation of negative feedback, and the optimization of electronics for the
creation of a feedback signal. The main characteristics of the angular
accelerometer, such as amplitude-frequency characteristics, self-noise and Allan
variance were experimentally measured. The obtained output parameters were
compared to its analogues and it showed perspectives for further development in
this field.
PMID- 29337877
TI - Virtual Environments for Visualizing Structural Health Monitoring Sensor
Networks, Data, and Metadata.
AB - Visualization of sensor networks, data, and metadata is becoming one of the most
pivotal aspects of the structural health monitoring (SHM) process. Without the
ability to communicate efficiently and effectively between disparate groups
working on a project, an SHM system can be underused, misunderstood, or even
abandoned. For this reason, this work seeks to evaluate visualization techniques
in the field, identify flaws in current practices, and devise a new method for
visualizing and accessing SHM data and metadata in 3D. More precisely, the work
presented here reflects a method and digital workflow for integrating SHM sensor
networks, data, and metadata into a virtual reality environment by combining
spherical imaging and informational modeling. Both intuitive and interactive,
this method fosters communication on a project enabling diverse practitioners of
SHM to efficiently consult and use the sensor networks, data, and metadata. The
method is presented through its implementation on a case study, Streicker Bridge
at Princeton University campus. To illustrate the efficiency of the new method,
the time and data file size were compared to other potential methods used for
visualizing and accessing SHM sensor networks, data, and metadata in 3D.
Additionally, feedback from civil engineering students familiar with SHM is used
for validation. Recommendations on how different groups working together on an
SHM project can create SHM virtual environment and convey data to proper
audiences, are also included.
PMID- 29337876
TI - Microenvironment Stimuli HGF and Hypoxia Differently Affected miR-125b and Ets-1
Function with Opposite Effects on the Invasiveness of Bone Metastatic Cells: A
Comparison with Breast Carcinoma Cells.
AB - We examined the influence of microenvironment stimuli on molecular events
relevant to the biological functions of 1833-bone metastatic clone and the
parental MDA-MB231 cells. (i) In both the cell lines, hepatocyte growth factor
(HGF) and the osteoblasts' biological products down regulated nuclear Ets-1
protein level in concomitance with endogenous miR-125b accumulation. In contrast,
under hypoxia nuclear Ets-1 was unchanged, notwithstanding the miR-125b increase.
(ii) Also, the 1833-cell invasiveness and the expression of Endothelin-1, the
target gene of Ets-1/HIF-1, showed opposite patterns under HGF and hypoxia. We
clarified the molecular mechanism(s) reproducing the high miR-125b levels with
the mimic in 1833 cells. Under hypoxia, the miR-125b mimic maintained a basal
level and functional Ets-1 protein, as testified by the elevated cell
invasiveness. However, under HGF ectopic miR-125b downregulated Ets-1 protein and
cell motility, likely involving an Ets-1-dominant negative form sensible to serum
conditions; Ets-1-activity inhibition by HGF implicated HIF-1alpha accumulation,
which drugged Ets-1 in the complex bound to the Endothelin-1 promoter.
Altogether, 1833-cell exposure to HGF would decrease Endothelin-1 transactivation
and protein expression, with the possible impairment of Endothelin-1-dependent
induction of E-cadherin, and the reversion towards an invasive phenotype: this
was favoured by Ets-1 overexpression, which inhibited HIF-1alpha expression and
HIF-1 activity. (iii) In MDA-MB231 cells, HGF strongly and rapidly decreased Ets
1, hampering invasiveness and reducing Ets-1-binding to Endothelin-1 promoter;
HIF-1alpha did not form a complex with Ets-1 and Endothelin-1-luciferase activity
was unchanged. Overall, depending on the microenvironment conditions and
endogenous miR-125b levels, bone-metastatic cells might switch from Ets-1
dependent motility towards colonization/growth, regulated by the balance between
Ets-1 and HIF-1.
PMID- 29337875
TI - Aux/IAA Gene Family in Plants: Molecular Structure, Regulation, and Function.
AB - Auxin plays a crucial role in the diverse cellular and developmental responses of
plants across their lifespan. Plants can quickly sense and respond to changes in
auxin levels, and these responses involve several major classes of auxin
responsive genes, including the Auxin/Indole-3-Acetic Acid (Aux/IAA) family, the
auxin response factor (ARF) family, small auxin upregulated RNA (SAUR), and the
auxin-responsive Gretchen Hagen3 (GH3) family. Aux/IAA proteins are short-lived
nuclear proteins comprising several highly conserved domains that are encoded by
the auxin early response gene family. These proteins have specific domains that
interact with ARFs and inhibit the transcription of genes activated by ARFs.
Molecular studies have revealed that Aux/IAA family members can form diverse
dimers with ARFs to regulate genes in various ways. Functional analyses of
Aux/IAA family members have indicated that they have various roles in plant
development, such as root development, shoot growth, and fruit ripening. In this
review, recently discovered details regarding the molecular characteristics,
regulation, and protein-protein interactions of the Aux/IAA proteins are
discussed. These details provide new insights into the molecular basis of the
Aux/IAA protein functions in plant developmental processes.
PMID- 29337878
TI - Tetrasubstituted Imidazolium Salts as Potent Antiparasitic Agents against African
and American Trypanosomiases.
AB - Imidazolium salts are privileged compounds in organic chemistry, and have
valuable biological properties. Recent studies show that symmetric imidazolium
salts with bulky moieties can display antiparasitic activity against T. cruzi.
After developing a facile methodology for the synthesis of tetrasubstituted
imidazolium salts from propargylamines and isocyanides, we screened a small
library of these adducts against the causative agents of African and American
trypanosomiases. These compounds display nanomolar activity against T. brucei and
low (or sub) micromolar activity against T. cruzi, with excellent selectivity
indexes and favorable molecular properties, thereby emerging as promising hits
for the treatment of Chagas disease and sleeping sickness.
PMID- 29337879
TI - Microwave Backscatter-Based Wireless Temperature Sensor Fabricated by an Alumina
Backed Au Slot Radiation Patch.
AB - A wireless and passive temperature sensor operating up to 800 degrees C is
proposed. The sensor is based on microwave backscatter RFID (radio frequency
identification) technology. A thin-film planar structure and simple working
principle make the sensor easy to operate under high temperature. In this paper,
the proposed high temperature sensor was designed, fabricated, and characterized.
Here the 99% alumina ceramic with a dimension of 40 mm * 40 mm * 1 mm was
prepared in micromechanics for fabrication of the sensor substrate. The
metallization of the Au slot patch was realized in magnetron sputtering with a
slot width of 2 mm and a slot length of 32 mm. The measured resonant frequency of
the sensor at 25 degrees C is 2.31 GHz. It was concluded that the resonant
frequency decreases with the increase in the temperature in range of 25-800
degrees C. It was shown that the average sensor sensitivity is 101.94 kHz/
degrees C.
PMID- 29337881
TI - Effects of Polypropylene Orientation on Mechanical and Heat Seal Properties of
Polymer-Aluminum-Polymer Composite Films for Pouch Lithium-Ion Batteries.
AB - In this study, polyamide-aluminum foil-polypropylene (PA-Al-PP) composite films
with different orientation status of the PP layer were prepared, and their
morphology, tensile, peeling and heat seal behavior were studied. The comparative
study of tensile and fracture behaviors of single-layer film of PA, Al and PP, as
well as the composite films of PA-Al, PP-Al and PA-Al-PP revealed that in PA-Al
PP composite film, the PA layer with the highest tensile strength can share the
tensile stress from the Al layer during stretching, while the PP layer with the
lowest tensile strength can prevent further development of the small cracks on
boundary of the Al layer during stretching. Moreover, the study of heat seal
behavior suggested that both the orientation status and the heat seal conditions
were important factors in determining the heat seal strength (HSS) and failure
behavior of the sample. Four failure types were observed, and a clear
correspondence between HSS and failure types was found. The results also
elucidated that for the composite film, only in the cases where the tensile
stress was efficiently released by each layer during HSS measurement could the
composite film exhibit desired high HSS that was even higher than its tensile
strength.
PMID- 29337880
TI - The Sodium and Potassium Content of the Most Commonly Available Street Foods in
Tajikistan and Kyrgyzstan in the Context of the FEEDCities Project.
AB - This cross-sectional study is aimed at assessing sodium (Na) and potassium (K)
content and the molar Na:K ratios of the most commonly available ready-to-eat
street foods in Tajikistan and Kyrgyzstan. Four different samples of each of
these foods were collected and 62 food categories were evaluated through
bromatological analysis. Flame photometry was used to quantify sodium and
potassium concentrations. The results show that home-made foods can be important
sources of sodium. In particular, main dishes and sandwiches, respectively,
contain more than 1400 and nearly 1000 mg Na in an average serving and provide
approximately 70% and 50% of the maximum daily recommended values. Wide ranges of
sodium content were found between individual samples of the same home-made food
collected from different vending sites from both countries. In industrial foods,
sodium contents ranged from 1 to 1511 mg/serving in Tajikistan, and from 19 to
658 mg/serving in Kyrgyzstan. Most Na:K ratios exceeded the recommended level of
1.0 and the highest ratios were found in home-made snacks (21.2) from Tajikistan
and industrial beverages (16.4) from Kyrgyzstan. These findings not only improve
data on the nutritional composition of foods in these countries, but may also
serve as baseline information for future policies and interventions.
PMID- 29337883
TI - Problematic Smartphone Use: Investigating Contemporary Experiences Using a
Convergent Design.
AB - Internet-enabled smartphones are increasingly ubiquitous in the Western world.
Research suggests a number of problems can result from mobile phone overuse,
including dependence, dangerous and prohibited use. For over a decade, this has
been measured by the Problematic Mobile Phone Use Questionnaire (PMPU-Q). Given
the rapid developments in mobile technologies, changes of use patterns and
possible problematic and addictive use, the aim of the present study was to
investigate and validate an updated contemporary version of the PMPU-Q (PMPU-Q
R). A mixed methods convergent design was employed, including a psychometric
survey (N = 512) alongside qualitative focus groups (N = 21), to elicit
experiences and perceptions of problematic smartphone use. The results suggest
the PMPU-Q-R factor structure can be updated to include smartphone dependence,
dangerous driving, and antisocial smartphone use factors. Theories of problematic
mobile phone use require consideration of the ubiquity and indispensability of
smartphones in the present day and age, particularly regarding use whilst driving
and in social interactions.
PMID- 29337882
TI - Functional Analysis of Promoters from Three Subtypes of the PI3K Family and Their
Roles in the Regulation of Lipid Metabolism by Insulin in Yellow Catfish
Pelteobagrus fulvidraco.
AB - In the present study, the length of 360, 1848 and 367 bp sequences of promoters
from three subtypes of PI3K family (PI3KCa, PI3KC2b and PI3KC3) of yellow catfish
Pelteobagrus fulvidraco were cloned and characterized. Bioinformatics analysis
revealed that PI3KCa, PI3KC2b and PI3KC3 had different structures in their core
promoter regions. The promoter regions of PI3KCa and PI3KC2b had CpG islands but
no CAAT and TATA box. In contrast, the promoter of PI3KC3 had the canonical TATA
and CAAT box but no CpG island. The binding sites of several transcription
factors, such as HNF1, STAT and NF-kappaB, were predicted on PI3KCa promoter. The
binding sites of transcription factors, such as FOXO1, PPAR-RXR, STAT, IK1, HNF6
and HNF3, were predicted on PI3KC2b promoter and the binding sites of FOXO1 and
STAT transcription factors were predicted on PI3KC3 promoter. Deletion analysis
indicated that these transcriptional factors were the potential regulators to
mediate the activities of their promoters. Subsequent mutation analysis and
electrophoretic mobility-shift assay (EMSA) demonstrated that HNF1 and IK1
directly bound with PI3KCa and PI3KC2b promoters and negatively regulated the
activities of PI3KCa and PI3KC2b promoters, respectively. Conversely, FOXO1
directly bound with the PI3KC2b and PI3KC3 promoters and positively regulated
their promoter activities. In addition, AS1842856 (AS, a potential FOXO1
inhibitor) incubation significantly reduced the relative luciferase activities of
several plasmids of PI3KC2b and PI3KC3 but did not significantly influence the
relative luciferase activities of the PI3KCa plasmids. Moreover, by using primary
hepatocytes from yellow catfish, AS incubation significantly down-regulated the
mRNA levels of PI3KCa, PI3KC2b and PI3KC3 and reduced triacylglyceride (TG)
accumulation and insulin-induced TG accumulation, as well as the activities and
the mRNA levels of several genes involved in lipid metabolism. Thus, the present
study offers new insights into the mechanisms for transcriptional regulation of
PI3Ks and for PI3Ks-mediated regulation of lipid metabolism by insulin in fish.
PMID- 29337884
TI - Monitoring Strategies of Earth Dams by Ground-Based Radar Interferometry: How to
Extract Useful Information for Seismic Risk Assessment.
AB - The aim of this paper is to describe how ground-based radar interferometry can
provide displacement measurements of earth dam surfaces and of vibration
frequencies of its main concrete infrastructures. In many cases, dams were built
many decades ago and, at that time, were not equipped with in situ sensors
embedded in the structure when they were built. Earth dams have scattering
properties similar to landslides for which the Ground-Based Synthetic Aperture
Radar (GBSAR) technique has been so far extensively applied to study ground
displacements. In this work, SAR and Real Aperture Radar (RAR) configurations are
used for the measurement of earth dam surface displacements and vibration
frequencies of concrete structures, respectively. A methodology for the
acquisition of SAR data and the rendering of results is described. The
geometrical correction factor, needed to transform the Line-of-Sight (LoS)
displacement measurements of GBSAR into an estimate of the horizontal
displacement vector of the dam surface, is derived. Furthermore, a methodology
for the acquisition of RAR data and the representation of displacement temporal
profiles and vibration frequency spectra of dam concrete structures is presented.
For this study a Ku-band ground-based radar, equipped with horn antennas having
different radiation patterns, has been used. Four case studies, using different
radar acquisition strategies specifically developed for the monitoring of earth
dams, are examined. The results of this work show the information that a Ku-band
ground-based radar can provide to structural engineers for a non-destructive
seismic assessment of earth dams.
PMID- 29337885
TI - Research on Geometric Calibration of Spaceborne Linear Array Whiskbroom Camera.
AB - The geometric calibration of a spaceborne thermal-infrared camera with a high
spatial resolution and wide coverage can set benchmarks for providing an accurate
geographical coordinate for the retrieval of land surface temperature. The
practice of using linear array whiskbroom Charge-Coupled Device (CCD) arrays to
image the Earth can help get thermal-infrared images of a large breadth with high
spatial resolutions. Focusing on the whiskbroom characteristics of equal time
intervals and unequal angles, the present study proposes a spaceborne linear
array-scanning imaging geometric model, whilst calibrating temporal system
parameters and whiskbroom angle parameters. With the help of the YG-14-China's
first satellite equipped with thermal-infrared cameras of high spatial resolution
China's Anyang Imaging and Taiyuan Imaging are used to conduct an experiment of
geometric calibration and a verification test, respectively. Results have shown
that the plane positioning accuracy without ground control points (GCPs) is
better than 30 pixels and the plane positioning accuracy with GCPs is better than
1 pixel.
PMID- 29337886
TI - Mechanical Activation of Adipose Tissue and Derived Mesenchymal Stem Cells: Novel
Anti-Inflammatory Properties.
AB - The adipose tissue is a source of inflammatory proteins, such as TNF, IL-6, and
CXCL8. Most of their production occurs in macrophages that act as scavengers of
dying adipocytes. The application of an orbital mechanical force for 6-10 min at
97 g to the adipose tissue, lipoaspirated and treated according to Coleman
procedures, abolishes the expression of TNF-alpha and stimulates the expression
of the anti-inflammatory protein TNF-stimulated gene-6 (TSG-6). This protein had
protective and anti-inflammatory effects when applied to animal models of
rheumatic diseases. We examined biopsy, lipoaspirate, and mechanically activated
fat and observed that in addition to the increased TSG-6, Sox2, Nanog, and Oct4
were also strongly augmented by mechanical activation, suggesting an effect on
stromal cell stemness. Human adipose tissue-derived mesenchymal stem cells
(hADSCs), produced from activated fat, grow and differentiate normally with
proper cell surface markers and chromosomal integrity, but their anti
inflammatory action is far superior compared to those mesenchymal stem cells
(MSCs) obtained from lipoaspirate. The expression and release of inflammatory
cytokines from THP-1 cells was totally abolished in mechanically activated
adipose tissue-derived hADSCs. In conclusion, we report that the orbital shaking
of adipose tissue enhances its anti-inflammatory properties, and derived MSCs
maintain such enhanced activity.
PMID- 29337887
TI - The Use of Municipal Solid Waste Incineration Ash in Various Building Materials:
A Belgian Point of View.
AB - Huge amounts of waste are being generated, and even though the incineration
process reduces the mass and volume of waste to a large extent, massive amounts
of residues still remain. On average, out of 1.3 billion tons of municipal solid
wastes generated per year, around 130 and 2.1 million tons are incinerated in the
world and in Belgium, respectively. Around 400 kT of bottom ash residues are
generated in Flanders, out of which only 102 kT are utilized here, and the rest
is exported or landfilled due to non-conformity to environmental regulations.
Landfilling makes the valuable resources in the residues unavailable and results
in more primary raw materials being used, increasing mining and related hazards.
Identifying and employing the right pre-treatment technique for the highest value
application is the key to attaining a circular economy. We reviewed the present
pre-treatment and utilization scenarios in Belgium, and the advancements in
research around the world for realization of maximum utilization are reported in
this paper. Uses of the material in the cement industry as a binder and cement
raw meal replacement are identified as possible effective utilization options for
large quantities of bottom ash. Pre-treatment techniques that could facilitate
this use are also discussed. With all the research evidence available, there is
now a need for combined efforts from incineration and the cement industry for
technical and economic optimization of the process flow.
PMID- 29337888
TI - Depression Symptom Patterns and Social Correlates among Chinese Americans.
AB - The aim of this study is to examine and compare the depression symptoms pattern
and social correlates in three groups: foreign-born Chinese Americans, US-born
Chinese Americans, and non-Hispanic whites. This study used data from the
Collaborative Psychiatric Epidemiology Surveys (CPES). The study sample consists
of 599 Chinese Americans (468 for the foreign-born and 121 for the US-born) and
4032 non-Hispanic whites. Factor analysis was used to examine the depression
symptom patterns by each subgroup. Four depression symptoms dimensions were
examined: negative affect, somatic symptoms, cognitive symptoms, and suicidality.
Logistic regression was used to investigate the effects of sociodemographic (age,
gender, marital status, and education), physical health condition, and social
relational factors (supports from and conflict with family and friends) on
specific types of depression symptoms separately for the three subgroups. The
findings showed little differences in depression symptom patterns but clear
variation in the social correlates to the four depression dimensions across the
three ethnocultural groups, foreign-born Chinese Americans, US-born Chinese
Americans, and non-Hispanic whites. Clinicians should take into account the
sociocultural factors of patients when making diagnosis and suggesting
treatments. In addition, psychiatrists, psychologists, or other mental health
service providers should offer treatment and coping suggestions based on the
specific symptom dimensions of patients, and patients' ethnocultural backgrounds.
PMID- 29337890
TI - Subcellular Reactive Oxygen Species (ROS) in Cardiovascular Pathophysiology.
AB - There exist two opposing perspectives regarding reactive oxygen species (ROS) and
their roles in angiogenesis and cardiovascular system, one that favors harmful
and causal effects of ROS, while the other supports beneficial effects. Recent
studies have shown that interaction between ROS in different sub-cellular
compartments plays a crucial role in determining the outcomes (beneficial vs.
deleterious) of ROS exposures on the vascular system. Oxidant radicals in one
cellular organelle can affect the ROS content and function in other sub-cellular
compartments in endothelial cells (ECs). In this review, we will focus on a
critical fact that the effects or the final phenotypic outcome of ROS exposure to
EC are tissue- or organ-specific, and depend on the spatial (subcellular
localization) and temporal (duration of ROS exposure) modulation of ROS levels.
PMID- 29337891
TI - Modeling of Dynamic Behavior of Carbon Fiber-Reinforced Polymer (CFRP) Composite
under X-ray Radiation.
AB - Carbon fiber-reinforced polymer (CFRP) composites have been increasingly used in
spacecraft applications. Spacecraft may encounter highenergy-density X-ray
radiation in outer space that can cause severe damage. To protect spacecraft from
such unexpected damage, it is essential to predict the dynamic behavior of CFRP
composites under X-ray radiation. In this study, we developed an in-house three
dimensional explicit finite element (FEM) code to investigate the dynamic
responses of CFRP composite under X-ray radiation for the first time, by
incorporating a modified PUFF equation-of-state. First, the blow-off impulse
(BOI) momentum of an aluminum panel was predicted by our FEM code and compared
with an existing radiation experiment. Then, the FEM code was utilized to
determine the dynamic behavior of a CFRP composite under various radiation
conditions. It was found that the numerical result was comparable with the
experimental one. Furthermore, the CFRP composite was more effective than the
aluminum panel in reducing radiation-induced pressure and BOI momentum. The
numerical results also revealed that a 1 keV X-ray led to vaporization of surface
materials and a high-magnitude compressive stress wave, whereas a low-magnitude
stress wave was generated with no surface vaporization when a 3 keV X-ray was
applied.
PMID- 29337892
TI - Improving Remote Health Monitoring: A Low-Complexity ECG Compression Approach.
AB - Recent advances in mobile technology have created a shift towards using battery
driven devices in remote monitoring settings and smart homes. Clinicians are
carrying out diagnostic and screening procedures based on the electrocardiogram
(ECG) signals collected remotely for outpatients who need continuous monitoring.
High-speed transmission and analysis of large recorded ECG signals are essential,
especially with the increased use of battery-powered devices. Exploring low-power
alternative compression methodologies that have high efficiency and that enable
ECG signal collection, transmission, and analysis in a smart home or remote
location is required. Compression algorithms based on adaptive linear predictors
and decimation by a factor B / K are evaluated based on compression ratio (CR),
percentage root-mean-square difference (PRD), and heartbeat detection accuracy of
the reconstructed ECG signal. With two databases (153 subjects), the new
algorithm demonstrates the highest compression performance ( CR = 6 and PRD =
1.88 ) and overall detection accuracy (99.90% sensitivity, 99.56% positive
predictivity) over both databases. The proposed algorithm presents an advantage
for the real-time transmission of ECG signals using a faster and more efficient
method, which meets the growing demand for more efficient remote health
monitoring.
PMID- 29337889
TI - Reactive Oxygen Species and Mitochondrial Dynamics: The Yin and Yang of
Mitochondrial Dysfunction and Cancer Progression.
AB - Mitochondria are organelles with a highly dynamic ultrastructure maintained by a
delicate equilibrium between its fission and fusion rates. Understanding the
factors influencing this balance is important as perturbations to mitochondrial
dynamics can result in pathological states. As a terminal site of nutrient
oxidation for the cell, mitochondrial powerhouses harness energy in the form of
ATP in a process driven by the electron transport chain. Contemporaneously,
electrons translocated within the electron transport chain undergo spontaneous
side reactions with oxygen, giving rise to superoxide and a variety of other
downstream reactive oxygen species (ROS). Mitochondrially-derived ROS can mediate
redox signaling or, in excess, cause cell injury and even cell death. Recent
evidence suggests that mitochondrial ultrastructure is tightly coupled to ROS
generation depending on the physiological status of the cell. Yet, the mechanism
by which changes in mitochondrial shape modulate mitochondrial function and redox
homeostasis is less clear. Aberrant mitochondrial morphology may lead to enhanced
ROS formation, which, in turn, may deteriorate mitochondrial health and further
exacerbate oxidative stress in a self-perpetuating vicious cycle. Here, we review
the latest findings on the intricate relationship between mitochondrial dynamics
and ROS production, focusing mainly on its role in malignant disease.
PMID- 29337893
TI - Soybean-Derived Phytoalexins Improve Cognitive Function through Activation of
Nrf2/HO-1 Signaling Pathway.
AB - As soy-derived glyceollins are known to induce antioxidant enzymes in various
types of cells and tissues, we hypothesized that the compounds could protect
neurons from damage due to reactive oxygen species (ROS). In order to examine the
neuroprotective effect of glyceollins, primary cortical neurons collected from
mice and mouse hippocampal HT22 cells were challenged with glutamate. Glyceollins
attenuated glutamate-induced cytotoxicity in primary cortical neuron isolated
from mice carrying wild-type nuclear factor (erythroid-derived 2)-like 2 (Nrf2),
but the compounds were ineffective in those isolated from Nrf2 knockout mice,
suggesting the involvement of the Nrf2 signaling pathway in glyceollin-mediated
neuroprotection. Furthermore, the inhibition of heme oxygenase-1 (HO-1), a major
downstream enzyme of Nrf2, abolished the suppressive effect of glyceollins
against glutamate-induced ROS production and cytotoxicity, confirming that
activation of HO-1 by glyceollins is responsible for the neuroprotection. To
examine whether glyceollins also improve cognitive ability, mice pretreated with
glyceollins were challenged with scopolamine and subjected to behavioral tests.
Glyceollins attenuated scopolamine-induced cognitive impairment of mice, but
failed to enhance memory in Nrf2 knockout mice, suggesting that the memory
enhancing effect is also mediated by the Nrf2 signaling pathway. Overall,
glyceollins showed neuroprotection against glutamate-induced damage, and
attenuated scopolamine-induced memory deficits in an Nrf2-dependent manner.
PMID- 29337894
TI - Inclinometer Assembly Error Calibration and Horizontal Image Correction in
Photoelectric Measurement Systems.
AB - Inclinometer assembly error is one of the key factors affecting the measurement
accuracy of photoelectric measurement systems. In order to solve the problem of
the lack of complete attitude information in the measurement system, this paper
proposes a new inclinometer assembly error calibration and horizontal image
correction method utilizing plumb lines in the scenario. Based on the principle
that the plumb line in the scenario should be a vertical line on the image plane
when the camera is placed horizontally in the photoelectric system, the direction
cosine matrix between the geodetic coordinate system and the inclinometer
coordinate system is calculated firstly by three-dimensional coordinate
transformation. Then, the homography matrix required for horizontal image
correction is obtained, along with the constraint equation satisfying the
inclinometer-camera system requirements. Finally, the assembly error of the
inclinometer is calibrated by the optimization function. Experimental results
show that the inclinometer assembly error can be calibrated only by using the
inclination angle information in conjunction with plumb lines in the scenario.
Perturbation simulation and practical experiments using MATLAB indicate the
feasibility of the proposed method. The inclined image can be horizontally
corrected by the homography matrix obtained during the calculation of the
inclinometer assembly error, as well.
PMID- 29337895
TI - A Coarse-Alignment Method Based on the Optimal-REQUEST Algorithm.
AB - In this paper, we proposed a coarse-alignment method for strapdown inertial
navigation systems based on attitude determination. The observation vectors,
which can be obtained by inertial sensors, usually contain various types of
noise, which affects the convergence rate and the accuracy of the coarse
alignment. Given this drawback, we studied an attitude-determination method named
optimal-REQUEST, which is an optimal method for attitude determination that is
based on observation vectors. Compared to the traditional attitude-determination
method, the filtering gain of the proposed method is tuned autonomously; thus,
the convergence rate of the attitude determination is faster than in the
traditional method. Within the proposed method, we developed an iterative method
for determining the attitude quaternion. We carried out simulation and turntable
tests, which we used to validate the proposed method's performance. The
experiment's results showed that the convergence rate of the proposed optimal
REQUEST algorithm is faster and that the coarse alignment's stability is higher.
In summary, the proposed method has a high applicability to practical systems.
PMID- 29337897
TI - Long-Term Mechanical Behavior of Nano Silica Sol Grouting.
AB - The longevity of grouting has a significant effect on the safe and sustainable
operation of many engineering projects. A 500-day experiment was carried out to
study the long-term mechanical behavior of nano silica sol grouting. The nano
silica sol was activated with different proportions of a NaCl catalyst and cured
under fluctuating temperature and humidity conditions. The mechanical parameters
of the grout samples were tested using an electrohydraulic uniaxial compression
tester and an improved Vicat instrument. Scanning electron microscope, X-ray
diffraction, and ultrasonic velocity tests were carried out to analyze the
strength change micro-mechanism. Tests showed that as the catalyst dosage in the
grout mix is decreased, the curves on the graphs showing changes in the weight
and geometric parameters of the samples over time could be divided into three
stages, a shrinkage stage, a stable stage, and a second shrinkage stage. The
catalyst improved the stability of the samples and reduced moisture loss.
Temperature rise was also a driving force for moisture loss. Uniaxial compressive
stress-strain curves for all of the samples were elastoplastic. The curves for
uniaxial compression strength and secant modulus plotted against time could be
divided into three stages. Sample brittleness increased with time and the
brittleness index increased with higher catalyst dosages in the latter part of
the curing time. Plastic strength-time curves exhibit allometric scaling. Curing
conditions mainly affect the compactness, and then affect the strength.
PMID- 29337896
TI - Caffeic Acid and Metformin Inhibit Invasive Phenotype Induced by TGF-beta1 in C
4I and HTB-35/SiHa Human Cervical Squamous Carcinoma Cells by Acting on Different
Molecular Targets.
AB - During the progression of epithelial cancer, the cells may lose epithelial
markers and gain mesenchymal phenotype via Epithelial-Mesenchymal Transition
(EMT). Such transformation of epithelial cancer cells to mesenchymal-like
characteristic benefits plasticity and supports their ability to migrate. The aim
of this study was to evaluate the influence of natural compound Caffeic Acid (CA)
alone and in combination with antidiabetic drug Metformin (Met) on metastatic
progression of two human cervical squamous cell cancer lines, C-4I and HTB
35/SiHa cells. EMT program was triggered by exposition of both epithelial cell
lines to TGF-beta1. Gene expression patterns related to epithelial/mesenchymal
phenotype were evaluated by Real-Time PCR analysis and the protein amount was
detected by western blot. The treatment of human squamous cancer cells with CA
and with Met, suppressed the motility of cells and the effect depended on a
particular cell line. Both compounds regulated the EMT process in C4-I and HTB-35
cells by interfering with different molecular targets. In TGF-beta1-stimulated C4
I cells, CA suppressed the expression of mesenchymal transcription factor SNAI1
which resulted in enhanced expression of epithelial markers E-cadherin, Occludin
and Claudin. Additionally, CA blocked MMP-9 and upregulated TIMP-1 expression, a
specific inhibitor of MMP-9. In HTB-35 cells stimulated with TGF-beta1, Met
decreased the expression of Vimentin. By suppressing hypoxia master regulator HIF
1alpha, Met caused downregulation of CAIX, an enzyme involved in metastasis of
aggressive malignant cells. In this study we showed that CA and Met inhibited EMT
process in cancer cells via different mechanisms. However, when applied together,
compounds exerted the greater effect on EMT than each compound alone. This is the
first report revealing that CA alone and co-treated with Met may reverse
mesenchymal phenotype of TGF-beta1-treated cervical tumor cells and we believe
that the use of the two small molecules may be considered as a potential
therapeutic approach for metastatic cervical cancer.
PMID- 29337899
TI - Synergistic Effects of Copper Sites on Apparent Stability of Multicopper Oxidase,
Fet3p.
AB - Saccharomyces cerevisiae Fet3p is a multicopper oxidase that contains three
cupredoxin-like domains and four copper ions located in three distinct metal
sites (T1 in domain 3; T2 and the binuclear T3 at the interface between domains 1
and 3). To probe the role of the copper sites in Fet3p thermodynamic stability,
we performed urea-induced unfolding experiments with holo-, apo- and three
partially-metallated (T1, T2 and T1/T2 sites depleted of copper) forms of Fet3p.
Using a combination of spectroscopic probes (circular dichroism, fluorescence
intensity and maximum, 8-anilinonaphthalene-1-sulfonic acid (ANS) emission,
oxidase activity and blue color), we reveal that all forms of Fet3p unfold in a
four-state reaction with two partially-folded intermediates. Using phase
diagrams, it emerged that Fet3p with all copper sites filled had a significantly
higher stability as compared to the combined contributions of the individual
copper sites. Hence, there is long-range inter-domain communication between
distal copper sites that contribute to overall Fet3p stability.
PMID- 29337900
TI - Age-Related Epigenetic Derangement upon Reprogramming and Differentiation of
Cells from the Elderly.
AB - Aging is a complex multi-layered phenomenon. The study of aging in humans is
based on the use of biological material from hard-to-gather tissues and highly
specific cohorts. The introduction of cell reprogramming techniques posed
promising features for medical practice and basic research. Recently, a growing
number of studies have been describing the generation of induced pluripotent stem
cells (iPSCs) from old or centenarian biologic material. Nonetheless,
Reprogramming techniques determine a profound remodelling on cell epigenetic
architecture whose extent is still largely debated. Given that cell epigenetic
profile changes with age, the study of cell-fate manipulation approaches on cells
deriving from old donors or centenarians may provide new insights not only on
regenerative features and physiology of these cells, but also on reprogramming
associated and age-related epigenetic derangement.
PMID- 29337902
TI - Cytokine Disturbances in Coronary Artery Ectasia Do Not Support Atherosclerosis
Pathogenesis.
AB - BACKGROUND: Coronary artery ectasia (CAE) is a rare disorder commonly associated
with additional features of atherosclerosis. In the present study, we aimed to
examine the systemic immune-inflammatory response that might associate CAE.
METHODS: Plasma samples were obtained from 16 patients with coronary artery
ectasia (mean age 64.9 +/- 7.3 years, 6 female), 69 patients with coronary artery
disease (CAD) and angiographic evidence for atherosclerosis (age 64.5 +/- 8.7
years, 41 female), and 140 controls (mean age 58.6 +/- 4.1 years, 40 female) with
normal coronary arteries. Samples were analyzed at Umea University Biochemistry
Laboratory, Sweden, using the V-PLEX Pro-Inflammatory Panel 1 (human) Kit.
Statistically significant differences (p < 0.05) between patient groups and
controls were determined using Mann-Whitney U-tests. RESULTS: The CAE patients
had significantly higher plasma levels of INF-gamma, TNF-alpha, IL-1beta, and IL
8 (p = 0.007, 0.01, 0.001, and 0.002, respectively), and lower levels of IL-2 and
IL-4 (p < 0.001 for both) compared to CAD patients and controls. The plasma
levels of IL-10, IL-12p, and IL-13 were not different between the three groups.
None of these markers could differentiate between patients with pure (n = 6) and
mixed with minimal atherosclerosis (n = 10) CAE. CONCLUSIONS: These results
indicate an enhanced systemic pro-inflammatory response in CAE. The profile of
this response indicates activation of macrophages through a pathway and trigger
different from those of atherosclerosis immune inflammatory response.
PMID- 29337901
TI - Transcriptional-Readthrough RNAs Reflect the Phenomenon of "A Gene Contains
Gene(s)" or "Gene(s) within a Gene" in the Human Genome, and Thus Are Not
Chimeric RNAs.
AB - Tens of thousands of chimeric RNAs, i.e., RNAs with sequences of two genes, have
been identified in human cells. Most of them are formed by two neighboring genes
on the same chromosome and are considered to be derived via transcriptional
readthrough, but a true readthrough event still awaits more evidence and trans
splicing that joins two transcripts together remains as a possible mechanism. We
regard those genomic loci that are transcriptionally read through as unannotated
genes, because their transcriptional and posttranscriptional regulations are the
same as those of already-annotated genes, including fusion genes formed due to
genetic alterations. Therefore, readthrough RNAs and fusion-gene-derived RNAs are
not chimeras. Only those two-gene RNAs formed at the RNA level, likely via trans
splicing, without corresponding genes as genomic parents, should be regarded as
authentic chimeric RNAs. However, since in human cells, procedural and
mechanistic details of trans-splicing have never been disclosed, we doubt the
existence of trans-splicing. Therefore, there are probably no authentic chimeras
in humans, after readthrough and fusion-gene derived RNAs are all put back into
the group of ordinary RNAs. Therefore, it should be further determined whether in
human cells all two-neighboring-gene RNAs are derived from transcriptional
readthrough and whether trans-splicing truly exists.
PMID- 29337903
TI - Use of Accelerometer Activity Monitors to Detect Changes in Pruritic Behaviors:
Interim Clinical Data on 6 Dogs.
AB - Veterinarians and pet owners have limited ability to assess pruritic behaviors in
dogs. This pilot study assessed the capacity of the Vetrax(r) triaxial
accelerometer to measure these behaviors in six dogs with pruritus likely due to
environmental allergens. Dogs wore the activity monitor for two weeks while
consuming their usual pet food (baseline), then for eight weeks while consuming a
veterinary-exclusive pet food for dogs with suspected non-food-related skin
conditions (Hill's Prescription Diet(r) Derm DefenseTM Canine dry food).
Veterinarians and owners completed questionnaires during baseline, phase 1 (days
1-28) and phase 2 (days 29-56) without knowledge of the activity data. Continuous
3-axis accelerometer data was processed using proprietary behavior recognition
algorithms and analyzed using general linear mixed models with false discovery
rate-adjusted p values. Veterinarian-assessed overall clinical signs of pruritus
were significantly predicted by scratching (beta 0.176, p = 0.008), head shaking
(beta 0.197, p < 0.001) and sleep quality (beta -0.154, p < 0.001), while owner
assessed quality of life was significantly predicted by scratching (beta -0.103,
p = 0.013) and head shaking (beta -0.146, p < 0.001). Among dogs exhibiting
pruritus signs eating the veterinary-exclusive food, the Vetrax(r) sensor
provided an objective assessment of clinically relevant pruritic behaviors that
agreed with owner and veterinarian reports.
PMID- 29337904
TI - Maternal Exposure to PM2.5 during Pregnancy Induces Impaired Development of
Cerebral Cortex in Mice Offspring.
AB - Air pollution is a serious environmental health problem closely related to the
occurrence of central nervous system diseases. Exposure to particulate matter
with an aerodynamic diameter less than or equal to 2.5 um (PM2.5) during
pregnancy may affect the growth and development of infants. The present study was
to investigate the effects of maternal exposure to PM2.5 during pregnancy on
brain development in mice offspring. Pregnant mice were randomly divided into
experimental groups of low-, medium-, or high-dosages of PM2.5, a mock-treated
group which was treated with the same amount of phosphate buffer solution (PBS),
and acontrol group which was untreated. The ethology of offspring mice on
postnatal days 1, 7, 14, 21, and 30, along with neuronal development and
apoptosis in the cerebral cortex were investigated. Compared with the control,
neuronal mitochondrial cristae fracture, changed autophagy characteristics,
significantly increased terminal deoxynucleotidyl transferase dUTP nick end
labeling (TUNEL) positive cell rate, and mRNA levels of apoptosis-related caspase
8 and caspase-9 were found in cerebral cortex of mice offspring from the
treatment groups, with mRNA levels of Bcl-2 and ratio of Bcl-2 to Bax decreased.
Treatment groups also demonstrated enhanced protein expressions of apoptosis
related cleaved caspase-3, cleaved caspase-8 and cleaved caspase-9, along with
declined proliferating cell nuclear antigen (PCNA), Bcl-2, and ratio of Bcl-2 to
Bax. Open field experiments and tail suspension experiments showed that exposure
to high dosage of PM2.5 resulted in decreased spontaneous activities but
increased static accumulation time in mice offspring, indicating anxiety,
depression, and social behavioral changes. Our results suggested that maternal
exposure to PM2.5 during pregnancy might interfere with cerebral cortex
development in mice offspring by affecting cell apoptosis.
PMID- 29337905
TI - The Role of miRNAs in the Pathophysiology of Liver Diseases and Toxicity.
AB - Both acute and chronic liver toxicity represents a major global health burden and
an important cause of morbidity and lethality worldwide. Despite epochal progress
in the treatment of hepatitis C virus infections, pharmacological treatment
strategies for most liver diseases are still limited and new targets for
prevention or treatment of liver disease are urgently needed. MicroRNAs (miRNAs)
represent a new class of highly conserved small non-coding RNAs that are involved
in the regulation of gene expression by targeting whole networks of so called
"targets". Previous studies have shown that the expression of miRNAs is
specifically altered in almost all acute and chronic liver diseases. In this
context, it was shown that miRNA can exert causal roles, being pro- or anti
inflammatory, as well as pro- or antifibrotic mediators or being oncogenes as
well as tumor suppressor genes. Recent data suggested a potential therapeutic use
of miRNAs by targeting different steps in the hepatic pathophysiology. Here, we
review the function of miRNAs in the context of acute and chronic liver diseases.
Furthermore, we highlight the potential role of circulating microRNAs in
diagnosis of liver diseases and discuss the major challenges and drawbacks that
currently prevent the use of miRNAs in clinical routine.
PMID- 29337906
TI - Specific Collagen Peptides Improve Bone Mineral Density and Bone Markers in
Postmenopausal Women-A Randomized Controlled Study.
AB - Introduction: Investigations in rodents as well as in vitro experiments have
suggested an anabolic influence of specific collagen peptides (SCP) on bone
formation and bone mineral density (BMD). The goal of the study was to
investigate the effect of 12-month daily oral administration of 5 g SCP vs.
placebo (CG: control group) on BMD in postmenopausal women with primary, age
related reduction in BMD. Methods: 131 women were enrolled in this randomized,
placebo-controlled double-blinded investigation. The primary endpoint was the
change in BMD of the femoral neck and the spine after 12 months. In addition,
plasma levels of bone markers-amino-terminal propeptide of type I collagen (P1NP)
and C-telopeptide of type I collagen (CTX 1)-were analysed. Results: A total of
102 women completed the study, but all subjects were included in the intention-to
treat (ITT) analysis (age 64.3 +/- 7.2 years; Body Mass Index, BMI 23.6 +/- 3.6
kg/m2; T-score spine -2.4 +/- 0.6; T-score femoral neck -1.4 +/- 0.5). In the SCP
group (n = 66), BMD of the spine and of the femoral neck increased significantly
compared to the control group (n = 65) (T-score spine: SCP +0.1 +/- 0.26; CG
0.03 +/- 0.18; ANCOVA p = 0.030; T-score femoral neck: SCP +0.09 +/- 0.24; CG
0.01 +/- 0.19; ANCOVA p = 0.003). P1NP increased significantly in the SCP group
(p = 0.007), whereas CTX 1 increased significantly in the control group (p =
0.011). Conclusions: These data demonstrate that the intake of SCP increased BMD
in postmenopausal women with primary, age-related reduction of BMD. In addition,
SCP supplementation was associated with a favorable shift in bone markers,
indicating increased bone formation and reduced bone degradation.
PMID- 29337907
TI - Few Sex Differences in Hospitalized Suicide Attempters Aged 70 and Above.
AB - Relatively little research attention has been paid to sex issues in late life
suicidal behaviour. The aim was to compare clinical characteristics of women and
men aged 70+ who were hospitalized after a suicide attempt. We hypothesized
higher depression and anxiety scores in women, and we expected to find that men
would more often attribute the attempt to health problems and compromised
autonomy. Participants (56 women and 47 men, mean age 80) were interviewed by a
psychologist. In addition to psychiatric and somatic health assessments,
participants responded to an open-ended question concerning attributions of the
attempt. There were no sex differences in depression and anxiety. Forty-five
percent of the men and 14% of the women had a history of substance use disorder
(p = 0.02). At least one serious physical disability was noted in 60.7% of the
women and 53.2% of the men (p = 0.55). Proportions attributing their attempt to
somatic illness did not differ (women, 14.5% vs. men 17.4%, p = 0.79), and
similar proportions attributed the attempt to reduced autonomy (women, 21.8% vs.
men, 26.1%, p = 0.64). We found strikingly similar figures for depression scores,
functional disability and attributions for attempting suicide in older men and
women. Larger studies are needed in diverse settings as sex differences might be
influenced by cultural context.
PMID- 29337909
TI - Salvia Species as Sources of Natural Products with Antiprotozoal Activity.
AB - Natural products from plants have been used since ancestral times to treat a wide
variety of diseases worldwide. Plants of the genus Salvia (Sage) have been
reported to be used for the prevention and treatment of various diseases and
ailments. In particular, some Salvia species have been used in traditional
medicine to treat diseases caused by protozoan parasites of the genera
Trypanosoma, Leishmania and Plasmodium and scientific studies have demonstrated
the activity of various isolated constituents from these plants against these
pathogens. The current review attempts to give a critical overview of published
information about the antiprotozoal activity of species of the genus Salvia and
their chemical constituents. It is meant to give a unified overview of these
results in order to avoid repetitions caused, e.g., by limited access to some
primary reports, and to stimulate further research to possibly facilitate the
development of new molecular leads against protozoal neglected tropical diseases
(NTDs) based on Salvia constituents.
PMID- 29337911
TI - Throughput Analysis on 3-Dimensional Underwater Acoustic Network with One-Hop
Mobile Relay.
AB - Underwater acoustic communication network (UACN) has been considered as an
essential infrastructure for ocean exploitation. Performance analysis of UACN is
important in underwater acoustic network deployment and management. In this
paper, we analyze the network throughput of three-dimensional randomly deployed
transmitter-receiver pairs. Due to the long delay of acoustic channels,
complicated networking protocols with heavy signaling overhead may not be
appropriate. In this paper, we consider only one-hop or two-hop transmission, to
save the signaling cost. That is, we assume the transmitter sends the data packet
to the receiver by one-hop direct transmission, or by two-hop transmission via
mobile relays. We derive the closed-form formulation of packet delivery rate with
respect to the transmission delay and the number of transmitter-receiver pairs.
The correctness of the derivation results are verified by computer simulations.
Our analysis indicates how to obtain a precise tradeoff between the delay
constraint and the network capacity.
PMID- 29337910
TI - Network-Based Methods for Identifying Key Active Proteins in the Extracellular
Electron Transfer Process in Shewanella oneidensis MR-1.
AB - Shewanella oneidensis MR-1 can transfer electrons from the intracellular
environment to the extracellular space of the cells to reduce the extracellular
insoluble electron acceptors (Extracellular Electron Transfer, EET). Benefiting
from this EET capability, Shewanella has been widely used in different areas,
such as energy production, wastewater treatment, and bioremediation. Genome-wide
proteomics data was used to determine the active proteins involved in activating
the EET process. We identified 1012 proteins with decreased expression and 811
proteins with increased expression when the EET process changed from inactivation
to activation. We then networked these proteins to construct the active protein
networks, and identified the top 20 key active proteins by network centralization
analysis, including metabolism- and energy-related proteins, signal and
transcriptional regulatory proteins, translation-related proteins, and the EET
related proteins. We also constructed the integrated protein interaction and
transcriptional regulatory networks for the active proteins, then found three
exclusive active network motifs involved in activating the EET process-Bi
feedforward Loop, Regulatory Cascade with a Feedback, and Feedback with a Protein
Protein Interaction (PPI)-and identified the active proteins involved in these
motifs. Both enrichment analysis and comparative analysis to the whole-genome
data implicated the multiheme c-type cytochromes and multiple signal processing
proteins involved in the process. Furthermore, the interactions of these motif
guided active proteins and the involved functional modules were discussed.
Collectively, by using network-based methods, this work reported a proteome-wide
search for the key active proteins that potentially activate the EET process.
PMID- 29337912
TI - Social Incentive Mechanism Based Multi-User Sensing Time Optimization in Co
Operative Spectrum Sensing with Mobile Crowd Sensing.
AB - Co-operative spectrum sensing emerging as a significant method to improve the
utilization of the spectrum needs sufficient sensing users to participate.
Existing related papers consider only the limited secondary users in current
sensing system and assume that they will always perform the co-operative spectrum
sensing out of obligation. However, this assumption is impractical in the
realistic situation where the secondary users are rational and they will not join
in the co-operative sensing process without a certain reward to compensate their
sensing energy consumption, especially the ones who have no data transmitting in
current time slot. To solve this problem, we take advantage of the mobile crowd
sensing to supply adequate co-operative sensing candidates, in which the sensing
users are not only the secondary users but also a crowd of widely distributed
mobile users equipped with personal spectrum sensors (such as smartphones,
vehicle sensors). Furthermore, a social incentive mechanism is also adapted to
motivate the participations of mobile sensing users. In this paper, we model the
interactions among the motivated sensing users as a co-operative game where they
adjust their own sensing time strategies to maximize the co-operative sensing
utility, which eventually guarantees the detection performance and prevents the
global sensing cost being too high. We prove that the game based optimization
problem is NP-hard and exists a unique optimal equilibrium. An improved
differential evolution algorithm is proposed to solve the optimization problem.
Simulation results prove the better performance in our proposed multi-user
sensing time optimization model and the proposed improved differential evolution
algorithm, respectively compared with the non-optimization model and the other
two typical equilibrium solution algorithms.
PMID- 29337913
TI - Proteomic Analysis and Identification of Possible Allergenic Proteins in Mature
Pollen of Populus tomentosa.
AB - Pollen grains from Populus tomentosa, a widely cultivated tree in northern area
of China, are considered to be an important aeroallergen causing severe allergic
diseases. To gain insight into their allergenic components, mature Populus
tomentosa pollen proteins were analyzed by two-dimensional gel electrophoresis (2
DE) and matrix-assisted laser desorption/ionization-time of flight mass
spectrometry (MALDI-TOF/TOF MS). A total of 412 spots from mature pollen were
resolved on pH 4-7 immobilized pH gradient (IPG) strips and 159 distinct proteins
were identified from 242 spots analyzed. The identified proteins were categorized
based on their functional role in the pollen, which included proteins involved in
energy regulation, protein fate, protein synthesis and processing, metabolism,
defense/stress responses, development and other functional categories. Moreover,
among the identified proteins, 27 proteins were identified as putative allergens
using the Structural Database of Allergenic Proteins (SDAP) tool and Allergen
Online. The expression patterns of these putative allergen genes indicate that
several of these genes are highly expressed in pollen. The identified putative
allergens have the potential to improve specific diagnosis and can be used to
develop vaccines for immunotherapy against poplar pollen allergy.
PMID- 29337914
TI - Acoustic Transducers as Passive Cooperative Targets for Wireless Sensing of the
Sub-Surface World: Challenges of Probing with Ground Penetrating RADAR.
AB - Passive wireless transducers are used as sensors, probed by a RADAR system. A
simple way to separate the returning signal from the clutter is to delay the
response, so that the clutter decays before the echoes are received. This can be
achieved by introducing a fixed delay in the sensor design. Acoustic wave
transducers are ideally suited as cooperative targets for passive, wireless
sensing. The incoming electromagnetic pulse is converted into an acoustic wave,
propagated on the sensor substrate surface, and reflected as an electromagnetic
echo. According to a known law, the acoustic wave propagation velocity depends on
the physical quantity under investigation, which is then measured as an echo
delay. Both conversions between electromagnetic and acoustic waves are based on
the piezoelectric property of the substrate of which the sensor is made.
Investigating underground sensing, we address the problems of using GPR (Ground
Penetrating RADAR) for probing cooperative targets. The GPR is a good candidate
for this application because it provides an electromagnetic source and receiver,
as well as echo recording tools. Instead of designing dedicated electronics, we
choose a commercially available, reliable and rugged instrument. The measurement
range depends on parameters like antenna radiation pattern, radio spectrum
matching between GPR and the target, antenna-sensor impedance matching and the
transfer function of the target. We demonstrate measurements at depths ranging
from centimeters to circa 1 m in a sandbox. In our application, clutter rejection
requires delays between the emitted pulse and echoes to be longer than in the
regular use of the GPR for geophysical measurements. This delay, and the accuracy
needed for sensing, challenge the GPR internal time base. In the GPR units we
used, the drift turns out to be incompatible with the targeted application. The
available documentation of other models and brands suggests that this is a rather
general limitation. We solved the problem by replacing the analog ramp generator
defining the time base with a fully digital solution, whose time accuracy and
stability relies on a quartz oscillator. The resulting stability is acceptable
for sub-surface cooperative sensor measurement.
PMID- 29337915
TI - Comparing Classic and Interval Analytical Hierarchy Process Methodologies for
Measuring Area-Level Deprivation to Analyze Health Inequalities.
AB - Deprivation indices are useful measures to study health inequalities. Different
techniques are commonly applied to construct deprivation indices, including multi
criteria decision methods such as the analytical hierarchy process (AHP). The
multi-criteria deprivation index for the city of Quito is an index in which
indicators are weighted by applying the AHP. In this research, a variation of
this index is introduced that is calculated using interval AHP methodology. Both
indices are compared by applying logistic generalized linear models and
multilevel models, considering self-reported health as the dependent variable and
deprivation and self-reported quality of life as the independent variables. The
obtained results show that the multi-criteria deprivation index for the city of
Quito is a meaningful measure to assess neighborhood effects on self-reported
health and that the alternative deprivation index using the interval AHP
methodology more thoroughly represents the local knowledge of experts and
stakeholders. These differences could support decision makers in improving health
planning and in tackling health inequalities in more deprived areas.
PMID- 29337916
TI - Real Time Cascade Impactor Based On Surface Acoustic Wave Delay Lines for PM10
and PM2.5 Mass Concentration Measurement.
AB - In this research, Surface Acoustic Wave (SAW) sensors are combined with a cascade
impactor to perform real time PM10 and PM2.5 mass concentration measurements. The
SAW sensors consist of 125 MHz delay lines based on Love waves propagating on an
AT-cut quartz substrate. The Love waves are guided on the substrate's surface
using a silica layer. SAW sensors themselves are not capable to discriminate
particles by their size, therefore, particle separation based on aerodynamic
diameter is achieved using a 3 Lpm dedicated cascade impactor. The latter was
designed to integrate the SAW sensors which are monitored using a phase shift
measurement. The collected particles impact on the acoustic sensor's surface
inducing a gravimetric effect that modifies the acoustic wave propagation
conditions. The resulted phase shift allows the measurement of the mass deposited
on the sensitive zone. The novel cascade impactor with SAW sensors as particle
collecting stages is exposed to different aerosols in the 0-150 MUg/m3
concentration range and proved to be able to detect and differentiate particles
based on their size in real time. The system's response was compared to a
commercial optical counter based on light scattering technology and was found to
be in good agreement with it.
PMID- 29337917
TI - The HydroColor App: Above Water Measurements of Remote Sensing Reflectance and
Turbidity Using a Smartphone Camera.
AB - HydroColor is a mobile application that utilizes a smartphone's camera and
auxiliary sensors to measure the remote sensing reflectance of natural water
bodies. HydroColor uses the smartphone's digital camera as a three-band
radiometer. Users are directed by the application to collect a series of three
images. These images are used to calculate the remote sensing reflectance in the
red, green, and blue broad wavelength bands. As with satellite measurements, the
reflectance can be inverted to estimate the concentration of absorbing and
scattering substances in the water, which are predominately composed of suspended
sediment, chlorophyll, and dissolved organic matter. This publication describes
the measurement method and investigates the precision of HydroColor's reflectance
and turbidity estimates compared to commercial instruments. It is shown that
HydroColor can measure the remote sensing reflectance to within 26% of a
precision radiometer and turbidity within 24% of a portable turbidimeter.
HydroColor distinguishes itself from other water quality camera methods in that
its operation is based on radiometric measurements instead of image color.
HydroColor is one of the few mobile applications to use a smartphone as a
completely objective sensor, as opposed to subjective user observations or color
matching using the human eye. This makes HydroColor a powerful tool for
crowdsourcing of aquatic optical data.
PMID- 29337918
TI - Polyacrylamide Ferrogels with Magnetite or Strontium Hexaferrite: Next Step in
the Development of Soft Biomimetic Matter for Biosensor Applications.
AB - Magnetic biosensors are an important part of biomedical applications of magnetic
materials. As the living tissue is basically a "soft matter." this study
addresses the development of ferrogels (FG) with micron sized magnetic particles
of magnetite and strontium hexaferrite mimicking the living tissue. The basic
composition of the FG comprised the polymeric network of polyacrylamide,
synthesized by free radical polymerization of monomeric acrylamide (AAm) in water
solution at three levels of concentration (1.1 M, 0.85 M and 0.58 M) to provide
the FG with varying elasticity. To improve FG biocompatibility and to prevent the
precipitation of the particles, polysaccharide thickeners-guar gum or xanthan gum
were used. The content of magnetic particles in FG varied up to 5.2 wt %
depending on the FG composition. The mechanical properties of FG and their
deformation in a uniform magnetic field were comparatively analyzed. FG filled
with strontium hexaferrite particles have larger Young's modulus value than FG
filled with magnetite particles, most likely due to the specific features of the
adhesion of the network's polymeric subchains on the surface of the particles. FG
networks with xanthan are stronger and have higher modulus than the FG with guar.
FG based on magnetite, contract in a magnetic field 0.42 T, whereas some FG based
on strontium hexaferrite swell. Weak FG with the lowest concentration of AAm
shows a much stronger response to a field, as the concentration of AAm governs
the Young's modulus of ferrogel. A small magnetic field magnetoimpedance sensor
prototype with Co68.6Fe3.9Mo3.0Si12.0B12.5 rapidly quenched amorphous ribbon
based element was designed aiming to develop a sensor working with a disposable
stripe sensitive element. The proposed protocol allowed measurements of the
concentration dependence of magnetic particles in gels using magnetoimpedance
responses in the presence of magnetite and strontium hexaferrite ferrogels with
xanthan. We have discussed the importance of magnetic history for the detection
process and demonstrated the importance of remnant magnetization in the case of
the gels with large magnetic particles.
PMID- 29337919
TI - Functional Impact of the N-terminal Arm of Proline Dehydrogenase from Thermus
thermophilus.
AB - Proline dehydrogenase (ProDH) is a ubiquitous flavoenzyme that catalyzes the
oxidation of proline to Delta1-pyrroline-5-carboxylate. Thermus thermophilus
ProDH (TtProDH) contains in addition to its flavin-binding domain an N-terminal
arm, consisting of helices alphaA, alphaB, and alphaC. Here, we report the
biochemical properties of the helical arm truncated TtProDH variants DeltaA,
DeltaAB, and DeltaABC, produced with maltose-binding protein as solubility tag.
All three truncated variants show similar spectral properties as TtProDH,
indicative of a conserved flavin-binding pocket. DeltaA and DeltaAB are highly
active tetramers that rapidly react with the suicide inhibitor N
propargylglycine. Removal of the entire N-terminal arm (DeltaABC) results in
barely active dimers that are incapable of forming a flavin adduct with N
propargylglycine. Characterization of V32D, Y35F, and V36D variants of DeltaAB
established that a hydrophobic patch between helix alphaC and helix alpha8 is
critical for TtProDH catalysis and tetramer stabilization.
PMID- 29337920
TI - Acute Traumatic Endotheliopathy in Isolated Severe Brain Injury and Its Impact on
Clinical Outcome.
AB - STUDY DESIGN: Prospective observational cohort. OBJECTIVE: To investigate the
difference in plasma levels of syndecan-1 (due to glycocalyx degradation) and
soluble thrombomodulin (due to endothelial damage) in isolated severe traumatic
brain injury (TBI) patients with/without early coagulopathy. A secondary
objective was to compare the effects of the degree of TBI endotheliopathy on
hospital mortality among patients with TBI-associated coagulopathy (TBI-AC).
METHODS: Data was prospectively collected on isolated severe TBI (sTBI) patients
with Glasgow Coma Scale (GCS) <=8 less than 12 h after injury admitted to a level
I trauma centre. Isolated sTBI patients with samples withdrawn prior to blood
transfusion were stratified by conventional coagulation tests as coagulopathic
(prothrombin time (PT) >= 16.7 s, international normalized ratio (INR) >= 1.27,
and activated partial thromboplastin time (aPTT) >= 28.8 s) and non
coagulopathic. Twenty healthy controls were also included. Plasma levels of
thrombomodulin and syndecan-1 were estimated by ELISA. With receiver operating
characteristic curve (ROC) analysis, we defined endotheliopathy as a syndecan-1
cut-off level that maximized the sum of sensitivity and specificity for
predicting TBI-AC. RESULTS: Inclusion criteria were met in 120 cases, with
subjects aged 35.5 +/- 12.6 years (88.3% males). TBI-AC was identified in 50
(41.6%) patients, independent of age, gender, and GCS, but there was an
association with acidosis (60%; p = 0.01). Following isolated sTBI, we found
insignificant changes in soluble thrombomodulin (sTM) levels between patients
with isolated TBI and controls, and sTM levels were lower in coagulopathic
compared to non-coagulopathic patients. Elevations in plasma syndecan-1 (ng/mL)
levels were seen compared to control (31.1(21.5-30.6) vs. 24.8(18.5-30.6); p =
0.08). Syndecan-1(ng/mL) levels were significantly elevated in coagulopathic
compared to non-coagulopathic patients (33.7(21.6-109.5) vs. 29.9(19.239.5); p =
0.03). Using ROC analysis (area under the curve = 0.61; 95% Confidence Interval
(CI) 0.50 to 0.72), we established a plasma syndecan-1 level cutoff of >=30.5
ng/mL (sensitivity % = 55.3, specificity % = 52.3), with a significant
association with TBI-associated coagulopathy. CONCLUSION: Subsequent to brain
injury, elevated syndecan-1 shedding and endotheliopathy may be associated with
early coagulation abnormalities. A syndecan-1 level >=30.5 ng/mL identified
patients with TBI-AC, and may be of importance in guiding management and clinical
decision-making.
PMID- 29337921
TI - Unified Compact ECC-AES Co-Processor with Group-Key Support for IoT Devices in
Wireless Sensor Networks.
AB - Security is a critical challenge for the effective expansion of all new emerging
applications in the Internet of Things paradigm. Therefore, it is necessary to
define and implement different mechanisms for guaranteeing security and privacy
of data interchanged within the multiple wireless sensor networks being part of
the Internet of Things. However, in this context, low power and low area are
required, limiting the resources available for security and thus hindering the
implementation of adequate security protocols. Group keys can save resources and
communications bandwidth, but should be combined with public key cryptography to
be really secure. In this paper, a compact and unified co-processor for enabling
Elliptic Curve Cryptography along to Advanced Encryption Standard with low area
requirements and Group-Key support is presented. The designed co-processor allows
securing wireless sensor networks with independence of the communications
protocols used. With an area occupancy of only 2101 LUTs over Spartan 6 devices
from Xilinx, it requires 15% less area while achieving near 490% better
performance when compared to cryptoprocessors with similar features in the
literature.
PMID- 29337922
TI - Underdetermined Wideband DOA Estimation for Off-Grid Sources with Coprime Array
Using Sparse Bayesian Learning.
AB - Sparse Bayesian learning (SBL) is applied to the coprime array for
underdetermined wideband direction of arrival (DOA) estimation. Using the
augmented covariance matrix, the coprime array can achieve a higher number of
degrees of freedom (DOFs) to resolve more sources than the number of physical
sensors. The sparse-based DOA estimation can deteriorate the detection and
estimation performance because the sources may be off the search grid no matter
how fine the grid is. This dictionary mismatch problem can be well resolved by
the SBL using fixed point updates. The SBL can automatically choose sparsity and
approximately resolve the non-convex optimizaton problem. Numerical simulations
are conducted to validate the effectiveness of the underdetermined wideband DOA
estimation via SBL based on coprime array. It is clear that SBL can obtain good
performance in detection and estimation compared to least absolute shrinkage and
selection operator (LASSO), simultaneous orthogonal matching pursuit least
squares (SOMP-LS) , simultaneous orthogonal matching pursuit total least squares
(SOMP-TLS) and off-grid sparse Bayesian inference (OGSBI).
PMID- 29337923
TI - Synergistic Antifungal, Allelopatic and Anti-Proliferative Potential of Salvia
officinalis L., and Thymus vulgaris L. Essential Oils.
AB - The current study aimed to investigate the chemical composition and the
synergistic potential of two essential oils (EOs), as obtained from Salvia
officinalis L. (SEO), and Thymus vulgaris L. (TEO). The antifungal potential was
tested in vitro against Fusarium graminearum (Fg 06_17), the herbicidal effect
was studied using weed seeds of Amaranthus retroflexus (ARET), Chenopodium album
(CALB), Echinochloa crus-galli (EGAL), but also wheat seeds (WS) of the Lovrin
variety and tomato seeds Saint-Pierre of the variety. The GC-MS profile
highlights that the mains compounds identified in SEO were: caryophyllene
(25.364%), camphene (14.139%), eucalyptol (13.902%), and beta-pinene (11.230%),
while in TEO, the predominant phytochemicals were: gamma-terpinene (68.415%) and
p-thymol (24.721%). The results indicated that the tested EOs alone as well as in
combination have allelopathic effect against investigated seeds, while the
synergistic effect of TEO and SEO in terms of fungal growth was demonstrated at a
level of 0.06%. Thyme and sage EOs exhibited in vitro anti-proliferative activity
on two melanoma cell lines, namely A375 human melanoma and B164A5 mouse melanoma
alone, as well as in combination. SEO was most effective in terms of decreasing
the cell viability of murine and human melanoma cell lines when compared to TEO.
PMID- 29337924
TI - Effect of Humid Aging on the Oxygen Adsorption in SnO2 Gas Sensors.
AB - To investigate the effect of aging at 580 degrees C in wet air (humid aging) on
the oxygen adsorption on the surface of SnO2 particles, the electric properties
and the sensor response to hydrogen in dry and humid atmospheres for SnO2
resistive-type gas sensors were evaluated. The electric resistance in dry and wet
atmospheres at 350 degrees C was strongly increased by humid aging. From the
results of oxygen partial pressure dependence of the electric resistance, the
oxygen adsorption equilibrium constants (K1; for O- adsorption, K2; for O2-
adsorption) were estimated on the basis of the theoretical model of oxygen
adsorption. The K1 and K2 in dry and wet atmospheres at 350 degrees C were
increased by humid aging at 580 degrees C, indicating an increase in the
adsorption amount of both O- and O2-. These results suggest that hydroxyl
poisoning on the oxygen adsorption is suppressed by humid aging. The sensor
response to hydrogen in dry and wet atmosphere at 350 degrees C was clearly
improved by humid aging. Such an improvement of the sensor response seems to be
caused by increasing the oxygen adsorption amount. Thus, the humid aging offers
an effective way to improve the sensor response of SnO2 resistive-type gas
sensors in dry and wet atmospheres.
PMID- 29337927
TI - The Plant Growth-Promoting Fungus (PGPF) Alternaria sp. A13 Markedly Enhances
Salvia miltiorrhiza Root Growth and Active Ingredient Accumulation under
Greenhouse and Field Conditions.
AB - Plant growth-promoting fungi (PGPF) have attracted considerable interest as bio
fertilisers due to their multiple beneficial effects on plant quantity and
quality and their positive relationship with the ecological environment.
Advancements in the development of PGPF for crops and economic plant cultivation
applications have been achieved, but such improvements for the use of PGPF with
popular medicinal herbs, such as Salvia miltiorrhiza, are rare. In this study, we
collected S. miltiorrhiza specimens inhabiting wild, semi-wild, farmland and pot
cultured areas in the Henan province of China and isolated endophytes from the
roots, shoots and leaves of these samples. Twenty-eight strains of the dominant
genus Alternaria were identified and selected as candidate PGPF. Under greenhouse
conditions, Alternaria sp. A13 simultaneously enhanced the dry root biomass and
secondary metabolite accumulation of S. miltiorrhiza as the optimal PGPF of the
28 candidate isolates. To further assess the interaction between S. miltiorrhiza
and Alternaria sp. A13, the effects on seedlings growth, active ingredient
accumulation, and the activity of key enzymes for effective biosynthetic pathways
were investigated over a period of six months under field conditions. Compared to
uninoculated seedlings, S. miltiorrhiza seedlings colonised by Alternaria sp. A13
showed significant increment of 140% in fresh weight, 138% in dry weight, and
enhancement in the contents of total phenolic acid, lithospermic acids A and B
(LAA and LAB, respectively) of 210%, 128% and 213%, respectively. Examination of
the related enzyme activities showed that the elicitation effect of A13 on LAB
accumulation correlated with cinnamic acid 4-hydroxylase (C4H) activity in the
phenylpropanoid pathway under field conditions. Our results confirmed that
Alternaria sp. A13 not only contributes to the stimulation of S. miltiorrhiza
root growth, but also boosts the secondary metabolism, thus demonstrating its
application potential as a bio-fertiliser for S. miltiorrhiza cultivation,
especially in areas outside of its native growth regions.
PMID- 29337925
TI - Plant Secondary Metabolites as Anticancer Agents: Successes in Clinical Trials
and Therapeutic Application.
AB - Cancer is a multistage process resulting in an uncontrolled and abrupt division
of cells and is one of the leading causes of mortality. The cases reported and
the predictions for the near future are unthinkable. Food and Drug Administration
data showed that 40% of the approved molecules are natural compounds or inspired
by them, from which, 74% are used in anticancer therapy. In fact, natural
products are viewed as more biologically friendly, that is less toxic to normal
cells. In this review, the most recent and successful cases of secondary
metabolites, including alkaloid, diterpene, triterpene and polyphenolic type
compounds, with great anticancer potential are discussed. Focusing on the ones
that are in clinical trial development or already used in anticancer therapy,
therefore successful cases such as paclitaxel and homoharringtonine (in clinical
use), curcumin and ingenol mebutate (in clinical trials) will be addressed. Each
compound's natural source, the most important steps in their discovery, their
therapeutic targets, as well as the main structural modifications that can
improve anticancer properties will be discussed in order to show the role of
plants as a source of effective and safe anticancer drugs.
PMID- 29337928
TI - Protective Factors in the Inuit Population of Nunavut: A Comparative Study of
People Who Died by Suicide, People Who Attempted Suicide, and People Who Never
Attempted Suicide.
AB - Epidemiological data shows an alarming prevalence of suicide in Aboriginal
populations around the world. In Canada, the highest rates are found in Inuit
communities. In this article, we present the findings of a secondary analysis
conducted with data previously collected as part of a larger study of
psychological autopsies conducted in Nunavut, Canada. The objective of this
secondary analysis was to identify protective factors in the Inuit population of
Nunavut by comparing people who died by suicide, people from the general
population who attempted suicide, and people from the general population who
never attempted suicide. This case-control study included 90 participants, with
30 participants in each group who were paired by birth date, sex, and community.
Content analysis was first conducted on the clinical vignettes from the initial
study in order to codify the presence of protective variables. Then, inferential
analyses were conducted to highlight differences between each group in regards to
protection. Findings demonstrated that (a) people with no suicide attempt have
more protective variables throughout their lifespan than people who died by
suicide and those with suicide attempts within the environmental, social, and
individual dimensions; (b) people with suicide attempts significantly differ from
the two other groups in regards to the use of services; and (c) protective
factors that stem from the environmental dimension show the greatest difference
between the three groups, being significantly more present in the group with no
suicide attempt. Considering these findings, interventions could focus on
enhancing environmental stability in Inuit communities as a suicide prevention
strategy.
PMID- 29337929
TI - Integrated Analyses Reveal Overexpressed Notch1 Promoting Porcine Satellite
Cells' Proliferation through Regulating the Cell Cycle.
AB - Notch signaling as a conserved cell fate regulator is involved in the regulation
of cell quiescence, proliferation, differentiation and postnatal tissue
regeneration. However, how Notch signaling regulates porcine satellite cells
(PSCs) has not been elucidated. We stably transfected Notch1 intracellular domain
(N1ICD) into PSCs to analyze the gene expression profile and miRNA-seq. The
analysis of the gene expression profile identified 295 differentially-expressed
genes (DEGs) in proliferating-N1ICD PSCs (P-N1ICD) and nine DEGs on
differentiating-N1ICD PSCs (D-N1ICD), compared with that in control groups (P
Control and D-Control, respectively). Analyzing the underlying function of DEGs
showed that most of the upregulated DEGs enriched in P-N1ICD PSCs are related to
the cell cycle. Forty-four and 12 known differentially-expressed miRNAs (DEMs)
were identified in the P-N1ICD PSCs and D-N1ICD PSCs group, respectively.
Furthermore, we constructed the gene-miRNA network of the DEGs and DEMs. In P
N1ICD PSCs, miR-125a, miR-125b, miR-10a-5p, ssc-miR-214, miR-423 and miR-149 are
downregulated hub miRNAs, whose corresponding hub genes are marker of
proliferation Ki-67 (MKI67) and nuclear receptor binding SET domain protein 2
(WHSC1). By contrast, miR-27a, miR-146a-5p and miR-221-3p are upregulated hub
miRNAs, whose hub genes are RUNX1 translocation partner 1 (RUNX1T1) and
fibroblast growth factor 2 (FGF2). All the hub miRNAs and genes are associated
with cell proliferation. Quantitative RT-PCR results are consistent with the gene
expression profile and miRNA-seq results. The results of our study provide
valuable information for understanding the molecular mechanisms underlying Notch
signaling in PSCs and skeletal muscle development.
PMID- 29337931
TI - Real Time Spectroscopic Ellipsometry Analysis of First Stage CuIn1-xGaxSe2
Growth: Indium-Gallium Selenide Co-Evaporation.
AB - Real time spectroscopic ellipsometry (RTSE) has been applied for in-situ
monitoring of the first stage of copper indium-gallium diselenide (CIGS) thin
film deposition by the three-stage co-evaporation process used for fabrication of
high efficiency thin film photovoltaic (PV) devices. The first stage entails the
growth of indium-gallium selenide (In1-xGax)2Se3 (IGS) on a substrate of Mo
coated soda lime glass maintained at a temperature of 400 degrees C. This is a
critical stage of CIGS deposition because a large fraction of the final film
thickness is deposited, and as a result precise compositional control is desired
in order to achieve the optimum performance of the resulting CIGS solar cell.
RTSE is sensitive to monolayer level film growth processes and can provide
accurate measurements of bulk and surface roughness layer thicknesses. These in
turn enable accurate measurements of the bulk layer optical response in the form
of the complex dielectric function epsilon = epsilon1 - iepsilon2, spectra. Here,
RTSE has been used to obtain the (epsilon1, epsilon2) spectra at the measurement
temperature of 400 degrees C for IGS thin films of different Ga contents (x)
deduced from different ranges of accumulated bulk layer thickness during the
deposition process. Applying an analytical expression in common for each of the
(epsilon1, epsilon2) spectra of these IGS films, oscillator parameters have been
obtained in the best fits and these parameters in turn have been fitted with
polynomials in x. From the resulting database of polynomial coefficients, the
(epsilon1, epsilon2) spectra can be generated for any composition of IGS from the
single parameter, x. The results have served as an RTSE fingerprint for IGS
composition and have provided further structural information beyond simply
thicknesses, for example information related to film density and grain size. The
deduced IGS structural evolution and the (epsilon1, epsilon2) spectra have been
interpreted as well in relation to observations from scanning electron
microscopy, X-ray diffractometry and energy-dispersive X-ray spectroscopy
profiling analyses. Overall the structural, optical and compositional analysis
possible by RTSE has assisted in understanding the growth and properties of three
stage CIGS absorbers for solar cells and shows future promise for enhancing cell
performance through monitoring and control.
PMID- 29337933
TI - Porpoise-Driven Life.
PMID- 29337930
TI - Asbestos-Related Disorders in Germany: Background, Politics, Incidence,
Diagnostics and Compensation.
AB - There was some limited use of asbestos at end of the 19th century in
industrialized countries including Germany, but its consumption dramatically
increased after World War II. The increase in use and exposure was followed by
the discovery of high numbers of asbestos-related diseases with a mean latency
period of about 38 years in Germany. The strong socio-political pressure from the
asbestos industry, its affiliated scientists and physicians has successfully
hindered regulatory measures and an asbestos ban for many years; a restrictive
stance that is still being unravelled in compensation litigation. This national
experience is compared with the situation in other industrialized countries and
against the backdrop of the constant efforts of the WHO to eliminate asbestos
related diseases worldwide.
PMID- 29337932
TI - High Number of Circulating Tumor Cells Predicts Poor Survival of Cutaneous
Melanoma Patients in China.
AB - BACKGROUND Melanoma is an aggressive cancer with complex etiology and poor
prognosis. Surgical resection is still the primary treatment of melanoma, but
shows limited efficacy in late-stage patients. Additionally, reliable prognostic
markers of skin melanoma patients are still lacking. Circulating tumor cells
(CTCs) have shown promise in predicting prognosis of multiple cancers. Evaluating
the prognostic value of CTC number in melanoma patients. MATERIAL AND METHODS
CTCs were isolated by immunomagnetic capture from 7.5-mL samples of blood from
100 patients with cutaneous melanoma. Baseline CTC number (pre-treatment) and
post-treatment CTC number were measured. Baseline CTC number and CTC number
alteration were correlated with clinicopathological features and survival.
RESULTS Forty-three (43%) patients had more than 6 CTCs, whereas 57 (57%) had 6
cells or less. High baseline CTC count was associated with deep local invasion,
lymph node metastasis, and distance metastasis, with P value of 0.003, 0.047, and
0.034, respectively. High baseline CTC count was also correlated with short
overall survival time and was considered as an independent prognostic factor (P
value=0.012, hazard ratio=2.262). CTC cell alteration was associated with
progression-free survival and disease-specific survival (with P values of 0.012
and 0.009, respectively). CONCLUSIONS Baseline CTC count was correlated with
adverse pathological features and was predictive of survival in melanoma
patients. Alteration of CTC count before and after treatment was an indicator of
therapy response and prognosis. Measuring the baseline and post-treatment CTC
counts is a powerful tool in monitoring melanoma progression, drug response, and
survival.
PMID- 29337934
TI - Depths of Space, Oceans and Politics.
PMID- 29337936
TI - Recommended.
PMID- 29337935
TI - Salmon Sex Moves Mountains.
PMID- 29337937
TI - Bee Sides.
PMID- 29337938
TI - A Universal Flu Vaccine Is Vital.
PMID- 29337939
TI - Greener Skies.
PMID- 29337941
TI - Letters.
PMID- 29337940
TI - Go Public or Perish.
PMID- 29337942
TI - Rivers of Plastic.
PMID- 29337943
TI - Troubled Waters.
PMID- 29337944
TI - The First Monster Black Holes.
PMID- 29337945
TI - The End of Night.
PMID- 29337946
TI - Misled Penguins.
PMID- 29337947
TI - Guardian Dogs of the Mongolian Steppe.
PMID- 29337948
TI - [Redacted].
PMID- 29337949
TI - The Robotic Artist Problem.
PMID- 29337950
TI - Quick Hits.
PMID- 29337951
TI - Fruitless Foragers.
PMID- 29337952
TI - Vanquishing Diabetes.
PMID- 29337953
TI - Diamond in the Rough.
PMID- 29337954
TI - Wearable Data.
PMID- 29337955
TI - Are Smartphones Really Destroying the Adolescent Brain?
PMID- 29337956
TI - Why Fake Operations Are a Good Thing.
PMID- 29337957
TI - Moon Shot.
PMID- 29337958
TI - 50, 100 &150 Years Ago.
PMID- 29337959
TI - The Tribalism of Truth.
PMID- 29337960
TI - Alvy's Error and the Meaning of Life.
PMID- 29337961
TI - How the evolution of multicellularity set the stage for cancer.
AB - Neoplastic growth and many of the hallmark properties of cancer are driven by the
disruption of molecular networks established during the emergence of
multicellularity. Regulatory pathways and molecules that evolved to impose
regulatory constraints upon networks established in earlier unicellular organisms
enabled greater communication and coordination between the diverse cell types
required for multicellularity, but also created liabilities in the form of points
of vulnerability in the network that when mutated or dysregulated facilitate the
development of cancer. These factors are usually overlooked in genomic analyses
of cancer, but understanding where vulnerabilities to cancer lie in the networks
of multicellular species would provide important new insights into how core
molecular processes and gene regulation change during tumourigenesis. We describe
how the evolutionary origins of genes influence their roles in cancer, and how
connections formed between unicellular and multicellular genes that act as key
regulatory hubs for normal tissue homeostasis can also contribute to malignant
transformation when disrupted. Tumours in general are characterised by increased
dependence on unicellular processes for survival, and major dysregulation of the
control structures imposed on these processes during the evolution of
multicellularity. Mounting molecular evidence suggests altered interactions at
the interface between unicellular and multicellular genes play key roles in the
initiation and progression of cancer. Furthermore, unicellular network regions
activated in cancer show high degrees of robustness and plasticity, conferring
increased adaptability to tumour cells by supporting effective responses to
environmental pressures such as drug exposure. Examining how the links between
multicellular and unicellular regions get disrupted in tumours has great
potential to identify novel drivers of cancer, and to guide improvements to
cancer treatment by identifying more effective therapeutic strategies. Recent
successes in targeting unicellular processes by novel compounds underscore the
logic of such approaches. Further gains could come from identifying genes at the
interface between unicellular and multicellular processes and manipulating the
communication between network regions of different evolutionary ages.
PMID- 29337962
TI - The relationship between right-sided tumour location, tumour microenvironment,
systemic inflammation, adjuvant therapy and survival in patients undergoing
surgery for colon and rectal cancer.
AB - BACKGROUND: There has been an increasing interest in the role of tumour location
in the treatment and prognosis of patients with colorectal cancer (CRC),
specifically in the adjuvant setting. Together with genomic data, this has led to
the proposal that right-sided and left-sided tumours should be considered as
distinct biological and clinical entities. The aim of the present study was to
examine the relationship between tumour location, tumour microenvironment,
systemic inflammatory response (SIR), adjuvant chemotherapy and survival in
patients undergoing potentially curative surgery for stage I-III colon and rectal
cancer. METHODS: Clinicopathological characteristics were extracted from a
prospective database. MMR and BRAF status was determined using
immunohistochemistry. The tumour microenvironment was assessed using routine H&E
pathological sections. SIR was assessed using modified Glasgow Prognostic Score
(mGPS), neutrophil:lymphocyte ratio (NLR), neutrophil:platelet score (NPS) and
lymphocyte:monocyte ratio (LMR). RESULTS: Overall, 972 patients were included.
The majority were over 65 years (68%), male (55%), TNM stage II/III (82%). In
all, 40% of patients had right-sided tumours and 31% had rectal cancers. Right
sided tumour location was associated with older age (P=0.001), deficient MMR
(P=0.005), higher T stage (P<0.001), poor tumour differentiation (P<0.001),
venous invasion (P=0.021), and high CD3+ within cancer cell nests (P=0.048).
Right-sided location was consistently associated with a high SIR, mGPS (P<0.001)
and NPS (P<0.001). There was no relationship between tumour location, adjuvant
chemotherapy (P=0.632) or cancer-specific survival (CSS; P=0.377). In those 275
patients who received adjuvant chemotherapy, right-sided location was not
associated with the MMR status (P=0.509) but was associated with higher T stage
(P=0.001), venous invasion (P=0.036), CD3+ at the invasive margin (P=0.033) and
CD3+ within cancer nests (P=0.012). There was no relationship between tumour
location, SIR or CSS in the adjuvant group. CONCLUSIONS: Right-sided tumour
location was associated with an elevated tumour lymphocytic infiltrate and an
elevated SIR. There was no association between tumour location and survival in
the non-adjuvant or adjuvant setting in patients undergoing potentially curative
surgery for stage I-III colon and rectal cancer.
PMID- 29337964
TI - Cancer therapy: A path of DSF destruction.
PMID- 29337963
TI - Phase I open-label study of afatinib plus vinorelbine in patients with solid
tumours overexpressing EGFR and/or HER2.
AB - BACKGROUND: This phase Ib study evaluated afatinib plus vinorelbine in patients
with advanced solid tumours overexpressing epidermal growth factor receptor
(EGFR) and/or human EGFR 2 (HER2). METHODS: Maximum tolerated doses (MTDs) were
determined for afatinib (20, 40 or 50 mg, once daily) combined with standard
intravenous vinorelbine (part A; 25 mg m-2 per week) or oral vinorelbine (part B;
60 mg m-2 per week, increased to 80 mg m-2 per week at week 3). Secondary end
points for expanded MTD cohorts included assessments of safety, pharmacokinetics,
tumour response and progression-free survival (PFS). RESULTS: The afatinib MTD
was 40 mg with intravenous (MTDA) and oral (MTDB) vinorelbine. The most frequent
cycle 1 dose-limiting toxicities were febrile neutropenia and diarrhoea,
consistent with individual safety profiles of vinorelbine and afatinib. Common
treatment-related adverse events included: diarrhoea (92.7%), asthenia (76.4%),
nausea (63.6%), neutropenia (56.4%) and vomiting (54.5%). No notable
pharmacokinetic interactions were observed. Best overall tumour response was
stable disease in part A (16 out of 28 patients), and partial response in part B
(3 out of 27 patients). Median PFS was 14.6 and 15.9 weeks for patients treated
at the MTDA and MTDB, including dose-escalation and expansion cohorts.
CONCLUSIONS: Afatinib in combination with intravenous or oral vinorelbine
demonstrated a manageable safety profile and antitumour activity at the MTD of 40
mg per day.
PMID- 29337965
TI - Synthetic biology: License to kill.
PMID- 29337966
TI - Drug development: Allosteric inhibitors hit USP7 hard.
PMID- 29337967
TI - Errata: Continuous directed evolution of aminoacyl-tRNA synthetases.
AB - This corrects the article DOI: 10.1038/nchembio.2474.
PMID- 29337968
TI - RNA Splicing: Making the cut.
PMID- 29337969
TI - Toward an orthogonal central dogma.
PMID- 29337970
TI - Cell biology: Eaten up from the inside.
PMID- 29337971
TI - Plant hormones: Metabolic end run to jasmonate.
PMID- 29337972
TI - Natural products: Tapping into personalized chemistry.
PMID- 29337973
TI - Visual perception of the osseous labyrinth rendered from micro-CT scans of the
petrous bone.
AB - Grayscale images comparing to the color images may have less of visual
information necessary for easy recognition of the anatomical structures. Although
micro-CT scanners deliver images of ultra-high resolution, application of false
colors to the rendered structures enhance their visual perception and allow for
quick delineation between them and surrounding bony matrix. This paper presents
differences of imaging of the osseous structures of the inner ear labyrinth using
pseudo-color volume rendering in contrast to grayscale volume rendering of the
micro-CT data. Applied procedures of image processing improved significantly
delineation between the bony matrix surrounding the cochlea and vestibule
rendered in the pseudo-colors than in grayscale.
PMID- 29337974
TI - Ferric reducing ability of plasma and assessment of selected plasma antioxidants
in adults with celiac disease.
AB - INTRODUCTION: Oxidative stress with an excessive free radical production and a
reduction in the activity of protective antioxidants is considered as one of the
mechanisms responsible for gluten toxicity. However, its role in celiac disease
(CD) is unclear. OBJECTIVES: Evaluation of plasma nonenzymatic antioxidant
capacity in patients with CD (both untreated patients and those receiving gluten
free diet [GFD]) by measuring the ferric reducing ability of plasma (FRAP) as
well as assessing selected plasma antioxidants. PATIENTS AND METHODS: The study
included 169 adult patients: 48 patients with untreated active CD, 72 patients
with CD on a GFD, and 49 healthy controls. In each group, we measured the serum
levels of selected antioxidants (uric acid, bilirubin, albumin, and vitamin E)
and used the FRAP assay to assess the total antioxidant capacity (TAC) of plasma.
In each patient, serological and histopathological activity of CD was also
evaluated. RESULTS: There were no significant differences in the TAC of plasma
measured with the FRAP assay between the study groups. Patients with CD had
higher uric acid levels compared with controls (p <0.001), while bilirubin levels
were lower in patients with active disease than in controls (p <0.05). Serum
vitamin E levels were lower in all patients with CD compared with controls (p
<0.01). CONCLUSIONS: The FRAP assay is not the method of choice for assessing the
TAC of plasma in patients with CD. Owing to high serum uric acid levels, the FRAP
assay results in these patients may be overestimated despite the reduced levels
of other plasma antioxidants.
PMID- 29337975
TI - Emotional states and sleep disorders in adolescent and young adult cystic
fibrosis patients.
AB - The aim of the study was to evaluate level of anxiety, depression and aggression
and the sleep quality among Polish adolescent and young adult suffering from
cystic fibrosis including the evaluation of their FEV1. The study involved 70
patients both male and female aged between 14 and 25 and suffering from cystic
fibrosis. Anxiety, depression and aggression were evaluated by means of Hospital
Anxiety and Depression Scale and the quality of sleep was examined following
Athens Insomnia Scale another aspect taken into consideration was patients' FEV1.
The data analysis was carried out by means of Chi2, Kolmogorov-Smirnov test,
Student's t-test, Fisher-Snedecor test, Pearson correlation coeficient. The level
of statistical significance was set at p <0.05. Anxiety was observed in 27
(38.6%) cases, depression in 17 (24.3%) and aggression in 46 (65.7%) cases.
Anxiety (p = 0.017) and aggression (p = 0.004) were significantly higher among
women than among men. 37 (52.8%) patients reported sleep disorders. The findings
proved that there is a connection between the quality of sleep and anxiety (r =
0.631; p = 0.000), depression (r = 0.621; p = 0.000) and aggression (r = 0.293; p
= 0.014). No significant relationship was found between the quality of sleep and
patients' expiratory volume. Emotional disorders such as anxiety, depression and
aggression as well as sleep disorders are commonly reported in patients suffering
from cystic fibrosis.
PMID- 29337976
TI - Ludwik Karol Teichmann (1823-1895).
AB - Ludwik Karol Teichmann was the last of gross anatomists. His magnificent work on
the lymphatic system gained him appreciation of the whole current scientific
world. Based on the unpublished materials authors wanted to commemorate one of
the greatest Polish and world anatomists with special regard to coming soon 150th
anniversary of Theatrum Anatomicum of Jagiellonian University Medical College.
PMID- 29337977
TI - Canaliform median raphe cysts (MRCs) lined by squamous epithelium in a 5 year old
male patient; report of a rare case and comprehensive review of the literature.
AB - : Median raphe cysts (MRCs) are rare, benign congenital lesions of unknown
origin, that can be found anywhere on the ventral side of the genital area,
between the urethral meatus and the anus. The rarity of our case is attributed to
the canaliform type, the scrotal and perineal localization and the epidermoid
epithelium. A 5 year old boy, with free perinatal and family history, was
admitted to our department as an outpatient due to the presence of an elongated
and mildly painful lesion in the middle of the scrotum, gradually increasing in
size. During physical examination the presence of a painful, subcutaneous,
yellowish lesion, extending from the scrotal to the perineal raphe, was
documented. Patient underwent elective surgery, under general endotracheal
anesthesia, and complete resection of the lesion was conducted. Histopathological
examination revealed the presence of a canaliform lesion consisting of five
cysts, lined by squamous epithelium and filled with lamellate keratin. IN
CONCLUSION: a) preventive removal of MRCs is considered as the safest treatment
option, in order to be avoided future, potential complications regarding
urination and sexual intercourse, b) if therapeutic intervention is delayed,
especially a er development of inflammation of MRCs, then the likelihood both of
iatrogenic injury to underlying structures, mainly to the penile or perineal
urethra, and of relapse a er resection increases significantly and c) if
orchidopexy precedes the development of MRCs, the possibility of presence of
ovarian serous border line tumor with Mullerian duct remnants should always be
excluded.
PMID- 29337978
TI - Penetration of formaldehyde based fixatives into heart.
AB - OBJECTIVES: To investigate the penetration depth of formaldehyde-based fixatives
into cardiac muscle samples over the course of fixation. BACKGROUND: Fixation is
the essential step in anatomical studies. However, very little is known about
penetration of most common fixatives into cardiac tissue. METHODS: A total of 40
heart samples were investigated. 4 study groups (n=10 in each case) were formed
in such manner they differed only in concentration and type of fixative (1) - 2%
formaldehyde phosphate-buffered solution (FPBS); (2) - 4% FPBS (formalin); (3) -
10% FPBS; (4) - alcoholic formalin. Samples were measured before fixation and in
the following time points: 24 hours, 72 hours, 168 hours. RESULTS: The
penetration depth differed significantly among studied fixatives (p<0.0001). 100%
penetration occurred in all samples after 72 hours in alcoholic formalin solution
and after 168 hours in 10% FPBS. After alcoholic formalin fixation, the tissue is
more brittle and sub-epicardial blisters were observed in some cases.
CONCLUSIONS: Alcoholic formalin solution is the fastest fixative among the
studied ones, however it has several adverse effects on tissue structure. It was
found that 10% FPBS is the best and a relatively fast fixative for cardiac
morphometric studies.
PMID- 29337979
TI - Analysis of pain and painless symptoms in temporomandibular joints dysfunction in
adult patients.
AB - : Recent years have shown an increase in the number of patients reporting for
treatment of pain due to musculoskeletal joint, associated with temporomandibular
joint dysfunction. Therefore, studies were undertaken, aimed at analyzing the
symptoms of the dysfunction, because of which patients come to the prosthetic
treatment. Aim of the thesis: The aim of the study was a retrospective analysis
of symptoms of temporomandibular joint dysfunction reported by patients diagnosed
with this problem. MATERIAL AND METHODS: The research material was a
retrospective medical records of 120 patients, aged 19 to 45 years who have taken
prosthetic treatment due to temporomandibular joint dysfunction in the Consulting
Room in Prosthetics Department in Krakow, from June 2015 to December 2016. During
the test patients, in addition to interviewing a physician, completed a personal
survey in their own study. The material has been divided into I group of patients
who reported pain form of dysfunction and II group, who had no symptoms of pain
within the stomatognatic system. The analysis covered type of symptoms, the share
of local factors (para-functions) and systemic, as well as the time a er which
the patients reported for the treatment of functional disorders since the
appearance of the first symptoms. RESULTS AND CONCLUSIONS: Analysis of the
research material showed that the main reason for reporting patients was pain in
one or both temporal joints of significant intensity (5 to 8 in VAS scale,)
accompanied by acoustic symptoms. A large group of questioners reported problems
with the range of jaw movement and head and face pain, as well as subjective
symptoms from the auditory, sight, neck, neck and shoulder areas.
PMID- 29337980
TI - The quantitative evaluation of the immunohistochemical expression of the
pituitary adenomas.
AB - BACKGROUND: The aim of this study was to evaluate morphometrically the pituitary
adenomas immunoexpression. METHODS: The cases of 72 patients were analyzed, who
underwent transsphenoidal surgery for pituitary adenomas. Subsequently, the
immunohistochemical pituitary hormone panel was applied including alpha- subunit
of the glycoprotein hormones. Immunohistochemical sections were analyzed
quantitatively with the help of morphometric grid. The percentage rate of the
immunoexpression was calculated separately for every single hormone. RESULTS: As
a result, 22 monohormonal adenomas (30.56%), 21 plurihormonal adenomas (29.17%),
21 immunonegative adenomas (29.17%) and 8 unreliable cases (11.11%) were
recognized. The immunopositivity for particular hormones was found as follows:
PRL and GH (25% each), alpha-SU (22.22%), ACTH (13.89%), LH and FSH (12.5% each),
and TSH (5.56%). An average percentage of immunoexpression in each positive
staining groups occurred as follows: for PRL - 59.98%, for GH - 53.97%, for ACTH
39.21%, for TSH - 25.05%, for LH - 37.3%, for FSH - 54.66%, for alpha-SU -
45.71. CONCLUSION: The morphometrical method utilizing the immunoexpression index
introduced in this study provided a very precise recognition of pituitary
adenomas pathology. This method may limit the subjectivity of a single researcher
and enable better comparison of the studies. The plurihormonality is a common
phenomenon, and immunohistochemical staining for all adenohypophyseal hormones is
obligatory in order to classify pituitary adenomas correctly. The awareness of an
operating neurosurgeon of the importance of meticulous collecting
histopathological material, especially in microadenoma cases, has essential
impact on further neuropathological evaluation and possibility of
immunohistochemical staining.
PMID- 29337981
TI - HSV encephalitis: is the insight of the clinician still crucial for the outcome?
AB - Herpes simplex virus (HSV) encephalitis is an acute infection of the Central
Nervous System (CNS). During the last two decades its incidence has a ten-fold
increase, while mortality rate exceeds 70%, if left undiagnosed and thus
untreated. Clinical manifestations, imaging studies, cerebrospinal fluid (CSF)
analysis and electroencephalogram (EEG) are the basis of diagnostic approach.
Even when CSF analysis seems normal, imaging studies are not specific and HSV
polymerase chain reaction (PCR) test is negative, the clinician should be more
aggressive, if clinical presentation is indicative for HSV encephalitis, by
administrating acyclovir early after patient's admission. The aim of this short
review article, after systematic research of the relevant up to date literature,
is to emphasize the insight of the clinician as for the early diagnosis and the
prompt therapeutic intervention, which are crucial for the outcome and vital for
the affected patient.
PMID- 29337982
TI - The efficacy of cardiopulmonary resuscitation, in a large city, based on Krakow's
Emergency Medical Service.
AB - INTRODUCTION: For many years, one of the biggest challenges of public healthcare
system, in the European Union are cardiovascular diseases. PURPOSE: The purpose
of this study was to analyze the variables influencing the specific aspects of
the chain of survival in a large city. METHODS: Patients included in this study
had to fulfill all of the following criteria: (1) patient had to experience an
out-of-hospital cardiac arrest (OHCA), (2) emergency medical team had to initiate
cardio-pulmonary resuscitation (CPR) at the site of the event. Data were
collected from the 1st of January to the 31st of December 2004. RESULT: In a time
period from the 1st of January to the 31st of December 2004 emergency medical
teams initiated 381 resuscitations. The incidence of OHCA in which CRP was
initiated was 50 events / 100 000 habitants. Spontaneous circulation was achieved
in 163 patients (42.8%). Thirty-day after the resuscitation 62 patients (16.3%)
were alive, and 52 patients (13.6%) were discharged alive from the hospital.
CONCLUSIONS: Analysis of collected data shows that return of spontaneous
circulation (ROSC) was achieved in 42.8% of patients, 16.3% survived at least 30
days following the event, and 13.6% of patients were discharged alive from the
hospital. These results are similar to findings from different studies conducted
in Poland.
PMID- 29337983
TI - Wor1 establishes opaque cell fate through inhibition of the general co-repressor
Tup1 in Candida albicans.
AB - The pathogenic fungus Candida albicans can undergo phenotypic switching between
two heritable states: white and opaque. This phenotypic plasticity facilitates
its colonization in distinct host niches. The master regulator WOR1 is
exclusively expressed in opaque phase cells. Positive feedback regulation by Wor1
on the WOR1 promoter is essential for opaque formation, however the underlying
mechanism of how Wor1 functions is not clear. Here, we use tandem affinity
purification coupled with mass spectrometry to identify Wor1-interacting
proteins. Tup1 and its associated complex proteins are found as the major factors
associated with Wor1. Tup1 occupies the same regions of the WOR1 promoter as Wor1
preferentially in opaque cells. Loss of Tup1 is sufficient to induce the opaque
phase, even in the absence of Wor1. This is the first such report of a bypass of
Wor1 in opaque formation. These genetic analyses suggest that Tup1 is a key
repressor of the opaque state, and Wor1 functions via alleviating Tup1 repression
at the WOR1 promoter. Opaque cells convert to white en masse at 37 degrees C. We
show that this conversion occurs only in the presence of glycolytic carbon
sources. The opaque state is stabilized when cells are cultured on non-glycolytic
carbon sources, even in a MTLa/alpha background. We further show that temperature
and carbon source affect opaque stability by altering the levels of Wor1 and Tup1
at the WOR1 promoter. We propose that Wor1 and Tup1 form the core regulatory
circuit controlling the opaque transcriptional program. This model provides
molecular insights on how C. albicans adapts to different host signals to undergo
phenotypic switching for colonization in distinct host niches.
PMID- 29337984
TI - Anteroposterior axis patterning by early canonical Wnt signaling during
hemichordate development.
AB - The Wnt family of secreted proteins has been proposed to play a conserved role in
early specification of the bilaterian anteroposterior (A/P) axis. This hypothesis
is based predominantly on data from vertebrate embryogenesis as well as planarian
regeneration and homeostasis, indicating that canonical Wnt (cWnt) signaling
endows cells with positional information along the A/P axis. Outside of these
phyla, there is strong support for a conserved role of cWnt signaling in the
repression of anterior fates, but little comparative support for a conserved role
in promotion of posterior fates. We further test the hypothesis by investigating
the role of cWnt signaling during early patterning along the A/P axis of the
hemichordate Saccoglossus kowalevskii. We have cloned and investigated the
expression of the complete Wnt ligand and Frizzled receptor complement of S.
kowalevskii during early development along with many secreted Wnt modifiers.
Eleven of the 13 Wnt ligands are ectodermally expressed in overlapping domains,
predominantly in the posterior, and Wnt antagonists are localized predominantly
to the anterior ectoderm in a pattern reminiscent of their distribution in
vertebrate embryos. Overexpression and knockdown experiments, in combination with
embryological manipulations, establish the importance of cWnt signaling for
repression of anterior fates and activation of mid-axial ectodermal fates during
the early development of S. kowalevskii. However, surprisingly, terminal
posterior fates, defined by posterior Hox genes, are unresponsive to manipulation
of cWnt levels during the early establishment of the A/P axis at late blastula
and early gastrula. We establish experimental support for a conserved role of Wnt
signaling in the early specification of the A/P axis during deuterostome body
plan diversification, and further build support for an ancestral role of this
pathway in early evolution of the bilaterian A/P axis. We find strong support for
a role of cWnt in suppression of anterior fates and promotion of mid-axial fates,
but we find no evidence that cWnt signaling plays a role in the early
specification of the most posterior axial fates in S. kowalevskii. This posterior
autonomy may be a conserved feature of early deuterostome axis specification.
PMID- 29337985
TI - Increased risk of ischemic heart disease, hypertension, and type 2 diabetes in
women with previous gestational diabetes mellitus, a target group in general
practice for preventive interventions: A population-based cohort study.
AB - BACKGROUND: Gestational diabetes mellitus (GDM) is associated with developing
type 2 diabetes, but very few studies have examined its effect on developing
cardiovascular disease. METHODS AND FINDINGS: We conducted a retrospective cohort
study utilizing a large primary care database in the United Kingdom. From 1
February 1990 to 15 May 2016, 9,118 women diagnosed with GDM were identified and
randomly matched with 37,281 control women by age and timing of pregnancy (up to
3 months). Adjusted incidence rate ratios (IRRs) with 95% confidence intervals
(CIs) were calculated for cardiovascular risk factors and cardiovascular disease.
Women with GDM were more likely to develop type 2 diabetes (IRR = 21.96; 95% CI
18.31-26.34) and hypertension (IRR = 1.85; 95% CI 1.59-2.16) after adjusting for
age, Townsend (deprivation) quintile, body mass index, and smoking. For ischemic
heart disease (IHD), the IRR was 2.78 (95% CI 1.37-5.66), and for cerebrovascular
disease 0.95 (95% CI 0.51-1.77; p-value = 0.87), after adjusting for the above
covariates and lipid-lowering medication and hypertension at baseline. Follow-up
screening for type 2 diabetes and cardiovascular risk factors was poor.
Limitations include potential selective documentation of severe GDM for women in
primary care, higher surveillance for outcomes in women diagnosed with GDM than
control women, and a short median follow-up postpartum period, with a small
number of outcomes for IHD and cerebrovascular disease. CONCLUSIONS: Women
diagnosed with GDM were at very high risk of developing type 2 diabetes and had a
significantly increased incidence of hypertension and IHD. Identifying this group
of women in general practice and targeting cardiovascular risk factors could
improve long-term outcomes.
PMID- 29337986
TI - The E2.65A mutation disrupts dynamic binding poses of SB269652 at the dopamine D2
and D3 receptors.
AB - The dopamine D2 and D3 receptors (D2R and D3R) are important targets for
antipsychotics and for the treatment of drug abuse. SB269652, a bitopic ligand
that simultaneously binds both the orthosteric binding site (OBS) and a secondary
binding pocket (SBP) in both D2R and D3R, was found to be a negative allosteric
modulator. Previous studies identified Glu2.65 in the SBP to be a key determinant
of both the affinity of SB269652 and the magnitude of its cooperativity with
orthosteric ligands, as the E2.65A mutation decreased both of these parameters.
However, the proposed hydrogen bond (H-bond) between Glu2.65 and the indole
moiety of SB269652 is not a strong interaction, and a structure activity
relationship study of SB269652 indicates that this H-bond may not be the only
element that determines its allosteric properties. To understand the structural
basis of the observed phenotype of E2.65A, we carried out molecular dynamics
simulations with a cumulative length of ~77 MUs of D2R and D3R wild-type and
their E2.65A mutants bound to SB269652. In combination with Markov state model
analysis and by characterizing the equilibria of ligand binding modes in
different conditions, we found that in both D2R and D3R, whereas the
tetrahydroisoquinoline moiety of SB269652 is stably bound in the OBS, the indole
2-carboxamide moiety is dynamic and only intermittently forms H-bonds with
Glu2.65. Our results also indicate that the E2.65A mutation significantly affects
the overall shape and size of the SBP, as well as the conformation of the N
terminus. Thus, our findings suggest that the key role of Glu2.65 in mediating
the allosteric properties of SB269652 extends beyond a direct interaction with
SB269652, and provide structural insights for rational design of SB269652
derivatives that may retain its allosteric properties.
PMID- 29337987
TI - Identification of a noncanonical function for ribose-5-phosphate isomerase A
promotes colorectal cancer formation by stabilizing and activating beta-catenin
via a novel C-terminal domain.
AB - Altered metabolism is one of the hallmarks of cancers. Deregulation of ribose-5
phosphate isomerase A (RPIA) in the pentose phosphate pathway (PPP) is known to
promote tumorigenesis in liver, lung, and breast tissues. Yet, the molecular
mechanism of RPIA-mediated colorectal cancer (CRC) is unknown. Our study
demonstrates a noncanonical function of RPIA in CRC. Data from the mRNAs of 80
patients' CRC tissues and paired nontumor tissues and protein levels, as well as
a CRC tissue array, indicate RPIA is significantly elevated in CRC. RPIA
modulates cell proliferation and oncogenicity via activation of beta-catenin in
colon cancer cell lines. Unlike its role in PPP in which RPIA functions within
the cytosol, RPIA enters the nucleus to form a complex with the adenomatous
polyposis coli (APC) and beta-catenin. This association protects beta-catenin by
preventing its phosphorylation, ubiquitination, and subsequent degradation. The C
terminus of RPIA (amino acids 290 to 311), a region distinct from its enzymatic
domain, is necessary for RPIA-mediated tumorigenesis. Consistent with results in
vitro, RPIA increases the expression of beta-catenin and its target genes, and
induces tumorigenesis in gut-specific promotor-carrying RPIA transgenic
zebrafish. Together, we demonstrate a novel function of RPIA in CRC formation in
which RPIA enters the nucleus and stabilizes beta-catenin activity and suggests
that RPIA might be a biomarker for targeted therapy and prognosis.
PMID- 29337988
TI - L-arginine supplementation reduces mortality and improves disease outcome in mice
infected with Trypanosoma cruzi.
AB - Chagas disease caused by Trypanosoma cruzi is a neglected disease that affects
about 7 million people in Latin America, recently emerging on other continents
due to migration. As infection in mice is characterized by depletion of plasma L
arginine, the effect on infection outcome was tested in mice with or without L
arginine supplementation and treatment with 1400W, a specific inhibitor of
inducible nitric oxide synthase (iNOS). We found that levels of L-arginine and
citrulline were reduced in the heart and plasma of infected mice, whereas levels
of asymmetric dimethylarginine, an endogenous iNOS inhibitor, were higher.
Moreover, L-arginine supplementation decreased parasitemia and heart parasite
burden, improving clinical score and survival. Nitric oxide production in heart
tissue and plasma was increased by L-arginine supplementation, while
pharmacological inhibition of iNOS yielded an increase in parasitemia and worse
clinical score. Interestingly, electrocardiograms improved in mice supplemented
with L-arginine, suggesting that it modulates infection and heart function and is
thus a potential biomarker of pathology. More importantly, L-arginine may be
useful for treating T. cruzi infection, either alone or in combination with other
antiparasitic drugs.
PMID- 29337989
TI - Differentially-dimensioned furrow formation by zygotic gene expression and the
MBT.
AB - Despite extensive work on the mechanisms that generate plasma membrane furrows,
understanding how cells are able to dynamically regulate furrow dimensions is an
unresolved question. Here, we present an in-depth characterization of furrow
behaviors and their regulation in vivo during early Drosophila morphogenesis. We
show that the deepening in furrow dimensions with successive nuclear cycles is
largely due to the introduction of a new, rapid ingression phase (Ingression II).
Blocking the midblastula transition (MBT) by suppressing zygotic transcription
through pharmacological or genetic means causes the absence of Ingression II, and
consequently reduces furrow dimensions. The analysis of compound chromosomes that
produce chromosomal aneuploidies suggests that multiple loci on the X, II, and
III chromosomes contribute to the production of differentially-dimensioned
furrows, and we track the X-chromosomal contribution to furrow lengthening to the
nullo gene product. We further show that checkpoint proteins are required for
furrow lengthening; however, mitotic phases of the cell cycle are not strictly
deterministic for furrow dimensions, as a decoupling of mitotic phases with
periods of active ingression occurs as syncytial furrow cycles progress. Finally,
we examined the turnover of maternal gene products and find that this is a minor
contributor to the developmental regulation of furrow morphologies. Our results
suggest that cellularization dynamics during cycle 14 are a continuation of
dynamics established during the syncytial cycles and provide a more nuanced view
of developmental- and MBT-driven morphogenesis.
PMID- 29337991
TI - HaSAPPy: A tool for candidate identification in pooled forward genetic screens of
haploid mammalian cells.
AB - Haploid cells are increasingly used for screening of complex pathways in animal
genomes. Hemizygous mutations introduced through viral insertional mutagenesis
can be directly selected for phenotypic changes. Here we present HaSAPPy a tool
for analysing sequencing datasets of screens using insertional mutations in large
pools of haploid cells. Candidate gene prediction is implemented through
identification of enrichment of insertional mutations after selection by
simultaneously evaluating several parameters. We have developed HaSAPPy for
analysis of genetic screens for silencing factors of X chromosome inactivation in
haploid mouse embryonic stem cells. To benchmark the performance, we further
analyse several datasets of genetic screens in human haploid cells for which
candidates have been validated. Our results support the effective candidate
prediction strategy of HaSAPPy. HaSAPPy is implemented in Python, licensed under
the MIT license, and is available from https://github.com/gdiminin/HaSAPPy.
PMID- 29337990
TI - Clustering gene expression time series data using an infinite Gaussian process
mixture model.
AB - Transcriptome-wide time series expression profiling is used to characterize the
cellular response to environmental perturbations. The first step to analyzing
transcriptional response data is often to cluster genes with similar responses.
Here, we present a nonparametric model-based method, Dirichlet process Gaussian
process mixture model (DPGP), which jointly models data clusters with a Dirichlet
process and temporal dependencies with Gaussian processes. We demonstrate the
accuracy of DPGP in comparison to state-of-the-art approaches using hundreds of
simulated data sets. To further test our method, we apply DPGP to published
microarray data from a microbial model organism exposed to stress and to novel
RNA-seq data from a human cell line exposed to the glucocorticoid dexamethasone.
We validate our clusters by examining local transcription factor binding and
histone modifications. Our results demonstrate that jointly modeling cluster
number and temporal dependencies can reveal shared regulatory mechanisms. DPGP
software is freely available online at
https://github.com/PrincetonUniversity/DP_GP_cluster.
PMID- 29337992
TI - Outstanding resistance and passivation behaviour of new Fe-Co metal-metal glassy
alloys in alkaline media.
AB - The electrochemical behavior of the oxide layers on two metal-metal glassy
alloys, Fe78Co9Cr10Mo2Al1 (VX9)and Fe49Co49V2 (VX50) (at.%), were studied using
electrochemical techniques including electrochemical frequency modulation (EFM),
electrochemical impedance spectroscopy (EIS) and cyclic polarization (CP)
measurements. The morphology and composition of the alloy surfaces were
investigated using X-ray photoelectron spectroscopy (XPS), scanning electron
microscopy (SEM) and atomic force microscopy (AFM). The corrosion rate and
surface roughness of both alloys increased as the concentration of NaOH in
aqueous solution was raised. The presence of some protective elements in the
composition of the alloys led to the formation of a spontaneous passive layer on
the alloy surface. The higher resistance values of both alloys were associated
with the magnitude of the dielectric properties of the passive films formed on
their surfaces. Both alloys are classified as having outstanding resistance to
corrosion, which results from the formation of a passive film that acts as an
efficient barrier to corrosion in alkaline solution.
PMID- 29337993
TI - The impact of ribosomal interference, codon usage, and exit tunnel interactions
on translation elongation rate variation.
AB - Previous studies have shown that translation elongation is regulated by multiple
factors, but the observed heterogeneity remains only partially explained. To
dissect quantitatively the different determinants of elongation speed, we use
probabilistic modeling to estimate initiation and local elongation rates from
ribosome profiling data. This model-based approach allows us to quantify the
extent of interference between ribosomes on the same transcript. We show that
neither interference nor the distribution of slow codons is sufficient to explain
the observed heterogeneity. Instead, we find that electrostatic interactions
between the ribosomal exit tunnel and specific parts of the nascent polypeptide
govern the elongation rate variation as the polypeptide makes its initial pass
through the tunnel. Once the N-terminus has escaped the tunnel, the hydropathy of
the nascent polypeptide within the ribosome plays a major role in modulating the
speed. We show that our results are consistent with the biophysical properties of
the tunnel.
PMID- 29337994
TI - A reassessment of the Montmaurin-La Niche mandible (Haute Garonne, France) in the
context of European Pleistocene human evolution.
AB - We here present a comparative study of the Montmaurin-LN Middle Pleistocene
mandible (Haute-Garonne, France). This mandible, of which its right and left
molar series are preserved in situ, was found in La Niche cave (Montmaurin's
karst system) in 1949, and was first attributed to the 'Mindel-Riss' interglacial
(= MIS 9 to 11) based on its geological context. Later studies based on
geological and faunal evidence have attributed the Montmaurin-LN mandible to MIS
7. Following a detailed morphological and metric comparative study of the
mandible in the 1970s, it was interpreted in the light of a still limited fossil
record and the prevailing paradigm back then. Waiting for geochronological
studies in the forthcoming years, here we review the main morphological and
metrical features of this mandible and its molars, which have been reassessed in
the framework of a remarkably enlarged Pleistocene fossil record since the
mandible was first described, and our current, more in-depth understanding of
human evolution in Europe. Using a selection of mandibular features with
potential taxonomic signal we have found that the Montmaurin-LN mandible shares
only a few derived traits with Neandertals. Our analyses reveal that this
mandible is more closely related to the ancient specimens from the African and
Eurasian Early and Middle Pleistocene, particularly due to the presence of
primitive features of the Homo clade. In contrast, the external morphology of the
molars is clearly similar to that of Neandertals. The results are assessed in the
light of the present competing hypotheses used to explain the European hominin
fossil record.
PMID- 29337995
TI - Evaluation of a community-based intervention to improve maternal and neonatal
health service coverage in the most rural and remote districts of Zambia.
AB - BACKGROUND: A community-based intervention comprising both men and women, known
as Safe Motherhood Action Groups (SMAGs), was implemented in four of Zambia's
poorest and most remote districts to improve coverage of selected maternal and
neonatal health interventions. This paper reports on outcomes in the coverage of
maternal and neonatal care interventions, including antenatal care (ANC), skilled
birth attendance (SBA) and postnatal care (PNC) in the study areas. METHODOLOGY:
Three serial cross-sectional surveys were conducted between 2012 and 2015 among
1,652 mothers of children 0-5 months of age using a 'before-and-after' evaluation
design with multi-stage sampling, combining probability proportional to size and
simple random sampling. Logistic regression and chi-square test for trend were
used to assess effect size and changes in measures of coverage for ANC, SBA and
PNC during the intervention. RESULTS: Mothers' mean age and educational status
were non-differentially comparable at all the three-time points. The odds of
attending ANC at least four times (aOR 1.63; 95% CI 1.38-1.99) and SBA (aOR 1.72;
95% CI 1.38-1.99) were at least 60% higher at endline than baseline surveillance.
A two-fold and four-fold increase in the odds of mothers receiving PNC from an
appropriate skilled provider (aOR 2.13; 95% CI 1.62-2.79) and a SMAG (aOR 4.87;
95% CI 3.14-7.54), respectively, were observed at endline. Receiving birth
preparedness messages from a SMAG during pregnancy (aOR 1.76; 95% CI, 1.20-2.19)
and receiving ANC from a skilled provider (aOR 4.01; 95% CI, 2.88-5.75) were
significant predictors for SBA at delivery and PNC. CONCLUSIONS: Strengthening
community-based action groups in poor and remote districts through the support of
mothers by SMAGs was associated with increased coverage of maternal and newborn
health interventions, measured through ANC, SBA and PNC. In remote and
marginalised settings, where the need is greatest, context-specific and
innovative task-sharing strategies using community health volunteers can be
effective in improving coverage of maternal and neonatal services and hold
promise for better maternal and child survival in poorly-resourced parts of sub
Saharan Africa.
PMID- 29337996
TI - Occupational exposure to human Mycobacterium bovis infection: A systematic
review.
AB - BACKGROUND: Mycobacterium bovis (M. bovis) is the main causative agent of bovine
zoonotic tuberculosis. The aim of this systematic review is to highlight the
occupational exposure to bovine tuberculosis due to M. bovis.
METHODOLOGY/PRINCIPAL FINDINGS: A computer based literature search was carried
out to identify papers published between January 2006 and March 2017. "PubMed,
Cochrane Library and Science Direct" databases were searched systematically.
Articles presenting the following properties were included: (i) focusing on M.
bovis; (ii) concerning occupational exposure to bovine tuberculosis. A quality
assessment was performed after selection of studies. Our search strategy
identified a total of 3,264 papers of which 29 studies met the inclusion
criteria. Of the 29 articles, 17 were cross-sectional studies (6 were of high
quality and scored in the range of 6-7, 11 were of moderate quality and scored in
the range 3-5), 10 were case reports, and 2 were reviews. Different occupational
fields exposing to the disease were described: livestock sector, particularly in
contact with dairy cattle (farmers, veterinaries and assistants, abattoir
workers) and working in contact with wildlife (hunters, taxidermists).
CONCLUSIONS: A specific guideline for occupational practitioners taking care of
employees exposed to bovine tuberculosis is warranted and should be tailored to
level of exposure. This review was intended to be the first step of such a
project. Articles were identified from various continents and countries with
different socio-economic situations, broadening our understanding of the
worldwide situation. Published data on occupational exposure in developed
countries are scarce. We had to extrapolate findings from countries with higher
prevalence of the disease.
PMID- 29337997
TI - Event based surveillance of Middle East Respiratory Syndrome Coronavirus (MERS-
CoV) in Bangladesh among pilgrims and travelers from the Middle East: An update
for the period 2013-2016.
AB - INTRODUCTION: Every year around 150,000 pilgrims from Bangladesh perform Umrah
and Hajj. Emergence and continuous reporting of MERS-CoV infection in Saudi
Arabia emphasize the need for surveillance of MERS-CoV in returning pilgrims or
travelers from the Middle East and capacity building of health care providers for
disease containment. The Institute of Epidemiology, Disease Control & Research
(IEDCR) under the Bangladesh Ministry of Health and Family welfare (MoHFW), is
responsible for MERS-CoV screening of pilgrims/ travelers returning from the
Middle East with respiratory illness as part of its outbreak investigation and
surveillance activities. METHODS: Bangladeshi travelers/pilgrims who returned
from the Middle East and presented with fever and respiratory symptoms were
studied over the period from October 2013 to June 2016. Patients with respiratory
symptoms that fulfilled the WHO MERS-CoV case algorithm were tested for MERS-CoV
and other respiratory tract viruses. Beside surveillance, case recognition
training was conducted at multiple levels of health care facilities across the
country in support of early detection and containment of the disease. RESULTS:
Eighty one suspected cases tested by real time PCR resulted in zero detection of
MERS-CoV infection. Viral etiology detected in 29.6% of the cases was
predominantly influenza A (H1N1 and H3N2), and influenza B infection (22%). Peak
testing occurred mostly following the annual Hajj season. CONCLUSIONS:
Respiratory tract infections in travelers/pilgrims returning to Bangladesh from
the Middle East are mainly due to influenza A and influenza B. Though MERS-CoV
was not detected in the 81 patients tested, continuous screening and surveillance
are essential for early detection of MERS-CoV infection and other respiratory
pathogens to prevent transmissions in hospital settings and within communities.
Awareness building among healthcare providers will help identify suspected cases.
PMID- 29337998
TI - Cognitive mechanisms for inferring the meaning of novel signals during
symbolisation.
AB - As participants repeatedly interact using graphical signals (as in a game of
Pictionary), the signals gradually shift from being iconic (or motivated) to
being symbolic (or arbitrary). The aim here is to test experimentally whether
this change in the form of the signal implies a concomitant shift in the
inferential mechanisms needed to understand it. The results show that, during
early, iconic stages, there is more reliance on creative inferential processes
associated with insight problem solving, and that the recruitment of these
cognitive mechanisms decreases over time. The variation in inferential mechanism
is not predicted by the sign's visual complexity or iconicity, but by its
familiarity, and by the complexity of the relevant mental representations. The
discussion explores implications for pragmatics, language evolution, and
iconicity research.
PMID- 29337999
TI - A dynamical systems approach for estimating phase interactions between rhythms of
different frequencies from experimental data.
AB - Synchronization of neural oscillations as a mechanism of brain function is
attracting increasing attention. Neural oscillation is a rhythmic neural activity
that can be easily observed by noninvasive electroencephalography (EEG). Neural
oscillations show the same frequency and cross-frequency synchronization for
various cognitive and perceptual functions. However, it is unclear how this
neural synchronization is achieved by a dynamical system. If neural oscillations
are weakly coupled oscillators, the dynamics of neural synchronization can be
described theoretically using a phase oscillator model. We propose an estimation
method to identify the phase oscillator model from real data of cross-frequency
synchronized activities. The proposed method can estimate the coupling function
governing the properties of synchronization. Furthermore, we examine the
reliability of the proposed method using time-series data obtained from numerical
simulation and an electronic circuit experiment, and show that our method can
estimate the coupling function correctly. Finally, we estimate the coupling
function between EEG oscillation and the speech sound envelope, and discuss the
validity of these results.
PMID- 29338000
TI - Progression of the first stage of spontaneous labour: A prospective cohort study
in two sub-Saharan African countries.
AB - BACKGROUND: Escalation in the global rates of labour interventions, particularly
cesarean section and oxytocin augmentation, has renewed interest in a better
understanding of natural labour progression. Methodological advancements in
statistical and computational techniques addressing the limitations of pioneer
studies have led to novel findings and triggered a re-evaluation of current
labour practices. As part of the World Health Organization's Better Outcomes in
Labour Difficulty (BOLD) project, which aimed to develop a new labour monitoring
to-action tool, we examined the patterns of labour progression as depicted by
cervical dilatation over time in a cohort of women in Nigeria and Uganda who gave
birth vaginally following a spontaneous labour onset. METHODS AND FINDINGS: This
was a prospective, multicentre, cohort study of 5,606 women with singleton,
vertex, term gestation who presented at <= 6 cm of cervical dilatation following
a spontaneous labour onset that resulted in a vaginal birth with no adverse birth
outcomes in 13 hospitals across Nigeria and Uganda. We independently applied
survival analysis and multistate Markov models to estimate the duration of labour
centimetre by centimetre until 10 cm and the cumulative duration of labour from
the cervical dilatation at admission through 10 cm. Multistate Markov and
nonlinear mixed models were separately used to construct average labour curves.
All analyses were conducted according to three parity groups: parity = 0 (n =
2,166), parity = 1 (n = 1,488), and parity = 2+ (n = 1,952). We performed
sensitivity analyses to assess the impact of oxytocin augmentation on labour
progression by re-examining the progression patterns after excluding women with
augmented labours. Labour was augmented with oxytocin in 40% of nulliparous and
28% of multiparous women. The median time to advance by 1 cm exceeded 1 hour
until 5 cm was reached in both nulliparous and multiparous women. Based on a 95th
percentile threshold, nulliparous women may take up to 7 hours to progress from 4
to 5 cm and over 3 hours to progress from 5 to 6 cm. Median cumulative duration
of labour indicates that nulliparous women admitted at 4 cm, 5 cm, and 6 cm
reached 10 cm within an expected time frame if the dilatation rate was >= 1
cm/hour, but their corresponding 95th percentiles show that labour could last up
to 14, 11, and 9 hours, respectively. Substantial differences exist between
actual plots of labour progression of individual women and the 'average labour
curves' derived from study population-level data. Exclusion of women with
augmented labours from the study population resulted in slightly faster labour
progression patterns. CONCLUSIONS: Cervical dilatation during labour in the
slowest-yet-normal women can progress more slowly than the widely accepted
benchmark of 1 cm/hour, irrespective of parity. Interventions to expedite labour
to conform to a cervical dilatation threshold of 1 cm/hour may be inappropriate,
especially when applied before 5 cm in nulliparous and multiparous women.
Averaged labour curves may not truly reflect the variability associated with
labour progression, and their use for decision-making in labour management should
be de-emphasized.
PMID- 29338001
TI - Modelling the large-scale yellow fever outbreak in Luanda, Angola, and the impact
of vaccination.
AB - BACKGROUND: Yellow fever (YF), transmitted via bites of infected mosquitoes, is a
life-threatening viral disease endemic to tropical and subtropical regions of
Africa and South America. YF has largely been controlled by widespread national
vaccination campaigns. Nevertheless, between December 2015 and August 2016, YF
resurged in Angola, quickly spread and became the largest YF outbreak for the
last 30 years. Recently, YF resurged again in Brazil (December 2016). Thus, there
is an urgent need to gain better understanding of the transmission pattern of YF.
MODEL: The present study provides a refined mathematical model, combined with
modern likelihood-based statistical inference techniques, to assess and
reconstruct important epidemiological processes underlying Angola's YF outbreak.
This includes the outbreak's attack rate, the reproduction number ([Formula: see
text]), the role of the mosquito vector, the influence of climatic factors, and
the unusual but noticeable appearance of two-waves in the YF outbreak. The model
explores actual and hypothetical vaccination strategies, and the impacts of
possible human reactive behaviors (e.g., response to media precautions).
FINDINGS: While there were 73 deaths reported over the study period, the model
indicates that the vaccination campaign saved 5.1-fold more people from death and
saved from illness 5.6-fold of the observed 941 cases. Delaying the availability
of the vaccines further would have greatly worsened the epidemic in terms of
increased cases and deaths. The analysis estimated a mean [Formula: see text] and
an attack rate of 0.09-0.15% (proportion of population infected) over the whole
period from December 2015 to August 2016. Our estimated lower and upper bounds of
[Formula: see text] are in line with previous studies. Unusually, [Formula: see
text] oscillated in a manner that was "delayed" with the reported deaths. High
recent number of deaths were associated (followed) with periods of relatively low
disease transmission and low [Formula: see text], and vice-versa. The time-series
of Luanda's YF cases suggest the outbreak occurred in two waves, a feature that
would have become far more prominent had there been no mass vaccination. The
waves could possibly be due to protective reactive behavioral changes of the
population affecting the mosquito population. The second wave could well be an
outcome of the March-April rainfall patterns in the 2016 El Nino year by creating
ideal conditions for the breeding of the mosquito vectors. The modelling
framework is a powerful tool for studying future YF epidemic outbreaks, and
provides a basis for future vaccination campaign evaluations.
PMID- 29338002
TI - The associations between adult body composition and abdominal adiposity outcomes,
and relative weight gain and linear growth from birth to age 22 in the Birth to
Twenty Plus cohort, South Africa.
AB - BACKGROUND: The growing prevalence of overweight and obesity in low- or middle
income countries precipitates the need to examine early life predictors of
adiposity. OBJECTIVES: To examine growth trajectories from birth, and
associations with adult body composition in the Birth to Twenty Plus Cohort,
Soweto, South Africa. METHODS: Complete data at year 22 was available for 1088
participants (536 males and 537 females). Conditional weight and height indices
were generated indicative of relative rate of growth between years 0-2, 2-5, 5-8,
8-18, and 18-22. Whole body composition was measured at year 22 (range 21-25
years) using dual energy x-ray absorptiometry (DXA). Total fat free soft tissue
mass (FFSTM), fat mass, and abdominal visceral adipose tissue (VAT) and
subcutaneous adipose tissue (SAT) were recorded. RESULTS: Birth weight was
positively associated with FFSTM and fat mass at year 22 (beta = 0.11, p<0.01 and
beta = 0.10, p<0.01 respectively). Relative weight gain from birth to year 22 was
positively associated with FFSTM, fat mass, VAT, and SAT at year 22. Relative
linear growth from birth to year 22 was positively associated with FFSTM at year
22. Relative linear growth from birth to year 2 was positively associated with
VAT at year 22. Being born small for gestational age and being stunted at age 2
years were inversely associated with FFSTM at year 22. CONCLUSIONS: The
importance of optimal birth weight and growth tempos during early life for later
life body composition, and the detrimental effects of pre- and postnatal growth
restriction are clear; yet contemporary weight-gain most strongly predicted adult
body composition. Thus interventions should target body composition trajectories
during childhood and prevent excessive weight gain in early adulthood.
PMID- 29338004
TI - Interrupting behaviour: Minimizing decision costs via temporal commitment and low
level interrupts.
AB - Ideal decision-makers should constantly assess all sources of information about
opportunities and threats, and be able to redetermine their choices promptly in
the face of change. However, perpetual monitoring and reassessment impose
inordinate sensing and computational costs, making them impractical for animals
and machines alike. The obvious alternative of committing for extended periods of
time to limited sensory strategies associated with particular courses of action
can be dangerous and wasteful. Here, we explore the intermediate possibility of
making provisional temporal commitments whilst admitting interruption based on
limited broader observation. We simulate foraging under threat of predation to
elucidate the benefits of such a scheme. We relate our results to diseases of
distractibility and roving attention, and consider mechanistic substrates such as
noradrenergic neuromodulation.
PMID- 29338003
TI - The prevalence of autosomal dominant polycystic kidney disease (ADPKD): A meta
analysis of European literature and prevalence evaluation in the Italian province
of Modena suggest that ADPKD is a rare and underdiagnosed condition.
AB - BACKGROUND AND OBJECTIVES: ADPKD is erroneously perceived as a not rare
condition, which is mainly due to the repeated citation of a mistaken
interpretation of old epidemiological data, as reported in the Dalgaard's work
(1957). Even if ADPKD is not a common condition, the correct prevalence of ADPKD
in the general population is uncertain, with a wide range of estimations reported
by different authors. In this work, we have performed a meta-analysis of
available epidemiological data in the European literature. Furthermore we
collected the diagnosis and clinical data of ADPKD in a province in the north of
Italy (Modena). We describe the point and predicted prevalence of ADPKD, as well
as the main clinical characteristics of ADPKD in this region. METHODS: We looked
at the epidemiological data according to specific parameters and criteria in the
Pubmed, CINAHL, Scopus and Web of Science databases. Data were summarized using
linear regression analysis. We collected patients' diagnoses in the Province of
Modena according to accepted clinical criteria and/or molecular analysis.
Predicted prevalence has been calculated through a logistic regression prediction
applied to the at-risk population. RESULTS: The average prevalence of ADPKD, as
obtained from 8 epidemiological studies of sufficient quality, is 2.7: 10,000
(CI95 = 0.73-4.67). The point prevalence of ADPKD in the province of Modena is
3.63: 10,000 (CI95 = 3.010-3.758). On the basis of the collected pedigrees and
identification of the at-risk subjects, the predicted prevalence in the Province
of Modena is 4.76: 10,000 (CI 95% = 4.109-4.918). CONCLUSION: As identified in
our study, point prevalence is comparable with the majority of the studies of
literature, while predicted prevalence (4.76: 10,000) generally appears higher
than in the previous estimates of the literature, with a few exceptions. Thus,
this could suggest that undiagnosed ADPKD subjects, as predicted by our approach,
could be relevant and will most likely require more clinical attention.
Nevertheless, our estimation, in addition to the averaged ones derived from
literature, not exceeding the limit of 5:10,000 inhabitants, are compatible with
the definition of rare disease adopted by the European Medicines Agency and Food
and Drug Administration.
PMID- 29338006
TI - A model for cooperative gating of L-type Ca2+ channels and its effects on cardiac
alternans dynamics.
AB - In ventricular myocytes, membrane depolarization during the action potential (AP)
causes synchronous activation of multiple L-type CaV1.2 channels (LTCCs), which
trigger the release of calcium (Ca2+) from the sarcoplasmic reticulum (SR). This
results in an increase in intracellular Ca2+ (Cai) that initiates contraction.
During pulsus alternans, cardiac contraction is unstable, going from weak to
strong in successive beats despite a constant heart rate. These cardiac alternans
can be caused by the instability of membrane potential (Vm) due to steep AP
duration (APD) restitution (Vm-driven alternans), instability of Cai cycling
(Ca2+-driven alternans), or both, and may be modulated by functional coupling
between clustered CaV1.2 (e.g. cooperative gating). Here, mathematical analysis
and computational models were used to determine how changes in the strength of
cooperative gating between LTCCs may impact membrane voltage and intracellular
Ca2+ dynamics in the heart. We found that increasing the degree of coupling
between LTCCs increases the amplitude of Ca2+ currents (ICaL) and prolongs AP
duration (APD). Increased AP duration is known to promote cardiac alternans, a
potentially arrhythmogenic substrate. In addition, our analysis shows that
increasing the strength of cooperative activation of LTCCs makes the coupling of
Ca2+ on the membrane voltage (Cai->Vm coupling) more positive and destabilizes
the Vm-Cai dynamics for Vm-driven alternans and Cai-driven alternans, but not for
quasiperiodic oscillation. These results suggest that cooperative gating of LTCCs
may have a major impact on cardiac excitation-contraction coupling, not only by
prolonging APD, but also by altering Cai->Vm coupling and potentially promoting
cardiac arrhythmias.
PMID- 29338005
TI - Inferring cell state by quantitative motility analysis reveals a dynamic state
system and broken detailed balance.
AB - Cell populations display heterogeneous and dynamic phenotypic states at multiple
scales. Similar to molecular features commonly used to explore cell
heterogeneity, cell behavior is a rich phenotypic space that may allow for
identification of relevant cell states. Inference of cell state from cell
behavior across a time course may enable the investigation of dynamics of
transitions between heterogeneous cell states, a task difficult to perform with
destructive molecular observations. Cell motility is one such easily observed
cell behavior with known biomedical relevance. To investigate heterogenous cell
states and their dynamics through the lens of cell behavior, we developed
Heteromotility, a software tool to extract quantitative motility features from
timelapse cell images. In mouse embryonic fibroblasts (MEFs), myoblasts, and
muscle stem cells (MuSCs), Heteromotility analysis identifies multiple motility
phenotypes within the population. In all three systems, the motility state
identity of individual cells is dynamic. Quantification of state transitions
reveals that MuSCs undergoing activation transition through progressive motility
states toward the myoblast phenotype. Transition rates during MuSC activation
suggest non-linear kinetics. By probability flux analysis, we find that this MuSC
motility state system breaks detailed balance, while the MEF and myoblast systems
do not. Balanced behavior state transitions can be captured by equilibrium
formalisms, while unbalanced switching between states violates equilibrium
conditions and would require an external driving force. Our data indicate that
the system regulating cell behavior can be decomposed into a set of attractor
states which depend on the identity of the cell, together with a set of
transitions between states. These results support a conceptual view of cell
populations as dynamical systems, responding to inputs from signaling pathways
and generating outputs in the form of state transitions and observable motile
behaviors.
PMID- 29338007
TI - Bilateral changes in afterhyperpolarization duration of spinal motoneurones in
post-stroke patients.
AB - This paper extends the observations presented in the previously published work on
the afterhyperpolarization (AHP) duration changes in motoneurones (MNs) on the
paretic (more affected) side of 11 post-stroke patients by the same analysis on
the non-paretic (less-affected) side. The estimated AHP duration for patients'
MNs supplying more-affected muscles was significantly longer than control values
and the elongation decreased with patient age and disorder duration. For MNs
supplying less-affected muscles, dependency of AHP duration on age was closer to
the control data, but the scatter was substantially bigger. However, the AHP
duration estimate of less-affected MNs tended to be longer than that of controls
in the short time elapsed since the stroke, and shorter than controls in the long
time. Our results thus suggest that the spinal MNs on both sides respond to the
cerebral stroke rapidly with prolongation of AHP duration, which tends to
normalize with time, in line with functional recovery. This suggestion is in
concert with the published research on post-stroke changes in brain hemispheres.
To our knowledge, these dependencies have never been investigated before. Since
the number of our data was limited, the observed trends should be verified in a
larger sample of patients and such a verification could take into account the
suggestions for data analysis that we provide in this paper. Our data are in line
with the earlier published research on MN firing characteristics post-stroke and
support the conclusion that the MUs of the muscles at the non-paretic side are
also affected and cannot be considered a suitable control for the MUs on the
paretic side.
PMID- 29338008
TI - Interactions between species introduce spurious associations in microbiome
studies.
AB - Microbiota contribute to many dimensions of host phenotype, including disease. To
link specific microbes to specific phenotypes, microbiome-wide association
studies compare microbial abundances between two groups of samples. Abundance
differences, however, reflect not only direct associations with the phenotype,
but also indirect effects due to microbial interactions. We found that microbial
interactions could easily generate a large number of spurious associations that
provide no mechanistic insight. Using techniques from statistical physics, we
developed a method to remove indirect associations and applied it to the largest
dataset on pediatric inflammatory bowel disease. Our method corrected the
inflation of p-values in standard association tests and showed that only a small
subset of associations is directly linked to the disease. Direct associations had
a much higher accuracy in separating cases from controls and pointed to
immunomodulation, butyrate production, and the brain-gut axis as important
factors in the inflammatory bowel disease.
PMID- 29338009
TI - Anti-angiogenic drug loaded liposomes: Nanotherapy for early atherosclerotic
lesions in mice.
AB - Fumagillin-loaded liposomes were injected into ApoE-KO mice. The animals were
divided into several groups to test the efficacy of this anti-angiogenic drug for
early treatment of atherosclerotic lesions. Statistical analysis of the lesions
revealed a decrease in the lesion size after 5 weeks of treatment.
PMID- 29338010
TI - Gypsophila bermejoi G. Lopez: A possible case of speciation repressed by
bioclimatic factors.
AB - Gypsophila bermejoi G. Lopez is an allopolyploid species derived from the
parental G. struthium L. subsp. struthium and G. tomentosa L. All these plants
are gypsophytes endemic to the Iberian Peninsula of particular ecological,
evolutionary and biochemical interest. In this study, we present evidence of a
possible repression on the process of G. bermejoi speciation by climatic factors.
We modelled the ecological niches of the three taxa considered here using a
maximum entropy approach and employing a series of bioclimatic variables.
Subsequently, we projected these models onto the geographical space of the
Iberian Peninsula in the present age and at two past ages: the Last Glacial
Maximum and the mid-Holocene period. Furthermore, we compared these niches using
the statistical method devised by Warren to calculate their degree of overlap. We
also evaluated the evolution of the bioclimatic habitat suitability at those
sites were the soil favors the growth of these species. Both the maximum entropy
model and the degree of overlap indicated that the ecological behavior of the
hybrid differs notably from that of the parental species. During the Last Glacial
Maximum, the two parental species appear to take refuge in the western coastal
strip of the Peninsula, a region in which there are virtually no sites where G.
bermejoi could potentially be found. However, in the mid-Holocene period the
suitability of G. bermejoi to sites with favorable soils shifts from almost null
to a strong adaptation, a clear change in this tendency. These results suggest
that the ecological niches of hybrid allopolyploids can be considerably different
to those of their parental species, which may have evolutionary and ecologically
relevant consequences. The data obtained indicate that certain bioclimatic
variables may possibly repress the processes by which new species are formed. The
difference in the ecological niche of G. bermejoi with respect to its parental
species prevented it from prospering during the Last Glacial Maximum. However,
the climatic change in the mid-Holocene period released this block and as such,
it permitted the new species to establish itself. Accordingly, we favor a recent
origin of the current populations of G. bermejoi.
PMID- 29338011
TI - Validation of Growth Layer Group (GLG) depositional rate using daily incremental
growth lines in the dentin of beluga (Delphinapterus leucas (Pallas, 1776))
teeth.
AB - Counts of Growth Layer Groups (GLGs) in the dentin of marine mammal teeth are
widely used as indicators of age. In most marine mammals, observations document
that GLGs are deposited yearly, but in beluga whales, some studies have supported
the view that two GLGs are deposited each year. Our understanding of beluga life
history differs substantially depending on assumptions regarding the timing of
GLG deposition; therefore, resolving this issue has important considerations for
population assessments. In this study, we used incremental lines that represent
daily pulses of dentin mineralization to test the hypothesis that GLGs in beluga
dentin are deposited on a yearly basis. Our estimate of the number of daily
growth lines within one GLG is remarkably close to 365 days within error,
supporting the hypothesis that GLGs are deposited annually in beluga. We show
that measurement of daily growth increments can be used to validate the time
represented by GLGs in beluga. Furthermore, we believe this methodology may have
broader applications to age estimation in other taxa.
PMID- 29338013
TI - Dynamical networks of influence in small group discussions.
AB - In many domains of life, business and management, numerous problems are addressed
by small groups of individuals engaged in face-to-face discussions. While
research in social psychology has a long history of studying the determinants of
small group performances, the internal dynamics that govern a group discussion
are not yet well understood. Here, we rely on computational methods based on
network analyses and opinion dynamics to describe how individuals influence each
other during a group discussion. We consider the situation in which a small group
of three individuals engages in a discussion to solve an estimation task. We
propose a model describing how group members gradually influence each other and
revise their judgments over the course of the discussion. The main component of
the model is an influence network-a weighted, directed graph that determines the
extent to which individuals influence each other during the discussion. In
simulations, we first study the optimal structure of the influence network that
yields the best group performances. Then, we implement a social learning process
by which individuals adapt to the past performance of their peers, thereby
affecting the structure of the influence network in the long run. We explore the
mechanisms underlying the emergence of efficient or maladaptive networks and show
that the influence network can converge towards the optimal one, but only when
individuals exhibit a social discounting bias by downgrading the relative
performances of their peers. Finally, we find a late-speaker effect, whereby
individuals who speak later in the discussion are perceived more positively in
the long run and are thus more influential. The numerous predictions of the model
can serve as a basis for future experiments, and this work opens research on
small group discussion to computational social sciences.
PMID- 29338012
TI - Using geospatial techniques to develop an emergency referral transport system for
suspected sepsis patients in Bangladesh.
AB - BACKGROUND: A geographic information system (GIS)-based transport network within
an emergency referral system can be the key to reducing health system delays and
increasing the chances of survival, especially during an emergency. We employed a
GIS to design an emergency transport system for the rapid transfer of pregnant or
early post-partum women, newborns, and children under 5 years of age with
suspected sepsis under the Interrupting Pathways to Sepsis Initiative (IPSI)
project. METHODS: A GIS database was developed by mapping the villages, roads,
and relevant physical features of the study area. A travel-time algorithm was
developed to incorporate the time taken by different modes of local transport to
reach the health complexes. These were used in a network analysis to identify the
shortest routes to the hospitals from the villages, which were categorized into
green, yellow, and red zones based on their proximity to the nearest hospitals to
provide transport facilities. An emergency call-in centre established for the
project managed the transport system, and its data was used to assess the uptake
of this transport system amongst distant communities. RESULTS: Fifteen pre
existing and two new routes were identified as the shortest routes to the health
complexes. The call-in centre personnel used this route information to direct
both patients and transport drivers to the nearest transport hubs or pick-up
points. Adherence with referral advice was high in areas where the IPSI transport
operated. Over the study period, the utilisation of the project's transport
doubled and referral compliance from distant zones similarly increased.
CONCLUSIONS: The GIS system created for this study facilitated rapid referral of
patients in emergency from distant zones, using locally available transport and
resources. The methodology described in this study to develop and implement an
emergency transport system can be applied in similar, rural, low-income country
settings.
PMID- 29338014
TI - Value of adding the renal pathological score to the kidney failure risk equation
in advanced diabetic nephropathy.
AB - BACKGROUND: There have been a limited number of biopsy-based studies on diabetic
nephropathy, and therefore the clinical importance of renal biopsy in patients
with diabetes in late-stage chronic kidney disease (CKD) is still debated. We
aimed to clarify the renal prognostic value of pathological information to
clinical information in patients with diabetes and advanced CKD. METHODS: We
retrospectively assessed 493 type 2 diabetics with biopsy-proven diabetic
nephropathy in four centers in Japan. 296 patients with stage 3-5 CKD at the time
of biopsy were identified and assigned two risk prediction scores for end-stage
renal disease (ESRD): the Kidney Failure Risk Equation (KFRE, a score composed of
clinical parameters) and the Diabetic Nephropathy Score (D-score, a score
integrated pathological parameters of the Diabetic Nephropathy Classification by
the Renal Pathology Society (RPS DN Classification)). They were randomized 2:1 to
development and validation cohort. Hazard Ratios (HR) of incident ESRD were
reported with 95% confidence interval (CI) of the KFRE, D-score and KFRE+D-score
in Cox regression model. Improvement of risk prediction with the addition of D
score to the KFRE was assessed using c-statistics, continuous net
reclassification improvement (NRI), and integrated discrimination improvement
(IDI). RESULTS: During median follow-up of 1.9 years, 194 patients developed
ESRD. The cox regression analysis showed that the KFRE,D-score and KFRE+D-score
were significant predictors of ESRD both in the development cohort and in the
validation cohort. The c-statistics of the D-score was 0.67. The c-statistics of
the KFRE was good, but its predictive value was weaker than that in the
miscellaneous CKD cohort originally reported (c-statistics, 0.78 vs. 0.90) and
was not significantly improved by adding the D-score (0.78 vs. 0.79, p = 0.83).
Only continuous NRI was positive after adding the D-score to the KFRE (0.4%; CI:
0.0-0.8%). CONCLUSIONS: We found that the predict values of the KFRE and the D
score were not as good as reported, and combining the D-score with the KFRE did
not significantly improve prediction of the risk of ESRD in advanced diabetic
nephropathy. To improve prediction of renal prognosis for advanced diabetic
nephropathy may require different approaches with combining clinical and
pathological parameters that were not measured in the KFRE and the RPS DN
Classification.
PMID- 29338015
TI - Exercise-induced circulating microRNA changes in athletes in various training
scenarios.
AB - BACKGROUND: The aim of the study was to compare selected extracellular miRNA
levels (miR-16, miR-21, miR-93 and miR-222 with the response to 8-week-long
explosive strength training (EXPL), hypertrophic strength training (HYP) and high
intensity interval training (HIIT). METHODS: 30 young male athletes of white
European origin (mean age: 22.5 +/- 4.06 years) recruited at the Faculty of
Sports Studies of Masaryk University were enrolled in this study. The study
participants were randomly assigned to three possible training scenarios: EXPL,
HYP or HITT and participated in 8-week-long program in given arm. Blood plasma
samples were collected at the baseline and at week 5 and 8 and anthropometric and
physical activity parameters were measured. Pre- and post-intervention
characteristics were compared and participants were further evaluated as
responders (RES) or non-responders (NRES). RES/NRES status was established for
the following characteristics: 300 degrees /s right leg extension (t300), 60
degrees /s right leg extension (t60), isometric extension (IE), vertical jump,
isometric extension of the right leg and body fat percentage (BFP). RESULTS: No
differences in miRNA levels were apparent between the intervention groups at
baseline. No statistically significant prediction role was observed using crude
univariate stepwise regression model analysis where RES/NRES status for t300,
t60, IE, vertical jump and pFM was used as a dependent variable and miR-21, miR
222, miR-16 and miR-93 levels at baseline were used as independent variables. The
baseline levels of miR-93 expressed an independent prediction role for responder
status based on isometric extension of the right leg (beta estimate 0.76, 95% CI:
-0.01; 1.53, p = 0.052). DISCUSSION: The results of the study indicate that 8
week-long explosive strength training, hypertrophic strength training and high
intensity interval training regimens are associated with significant changes in
miR-16, mir-21, miR-222 and miR-93 levels compared to a baseline in athletic
young men.
PMID- 29338016
TI - Ultrasound-mediated delivery and distribution of polymeric nanoparticles in the
normal brain parenchyma of a metastatic brain tumour model.
AB - The treatment of brain diseases is hindered by the blood-brain barrier (BBB)
preventing most drugs from entering the brain. Focused ultrasound (FUS) with
microbubbles can open the BBB safely and reversibly. Systemic drug injection
might induce toxicity, but encapsulation into nanoparticles reduces accumulation
in normal tissue. Here we used a novel platform based on poly(2-ethyl-butyl
cyanoacrylate) nanoparticle-stabilized microbubbles to permeabilize the BBB in a
melanoma brain metastasis model. With a dual-frequency ultrasound transducer
generating FUS at 1.1 MHz and 7.8 MHz, we opened the BBB using nanoparticle
microbubbles and low-frequency FUS, and applied high-frequency FUS to generate
acoustic radiation force and push nanoparticles through the extracellular matrix.
Using confocal microscopy and image analysis, we quantified nanoparticle
extravasation and distribution in the brain parenchyma. We also evaluated
haemorrhage, as well as the expression of P-glycoprotein, a key BBB component.
FUS and microbubbles distributed nanoparticles in the brain parenchyma, and the
distribution depended on the extent of BBB opening. The results from acoustic
radiation force were not conclusive, but in a few animals some effect could be
detected. P-glycoprotein was not significantly altered immediately after
sonication. In summary, FUS with our nanoparticle-stabilized microbubbles can
achieve accumulation and displacement of nanoparticles in the brain parenchyma.
PMID- 29338017
TI - Comparative genomics identifies distinct lineages of S. Enteritidis from
Queensland, Australia.
AB - Salmonella enterica is a major cause of gastroenteritis and foodborne illness in
Australia where notification rates in the state of Queensland are the highest in
the country. S. Enteritidis is among the five most common serotypes reported in
Queensland and it is a priority for epidemiological surveillance due to concerns
regarding its emergence in Australia. Using whole genome sequencing, we have
analysed the genomic epidemiology of 217 S. Enteritidis isolates from Queensland,
and observed that they fall into three distinct clades, which we have
differentiated as Clades A, B and C. Phage types and MLST sequence types differed
between the clades and comparative genomic analysis has shown that each has a
unique profile of prophage and genomic islands. Several of the phage regions
present in the S. Enteritidis reference strain P125109 were absent in Clades A
and C, and these clades also had difference in the presence of pathogenicity
islands, containing complete SPI-6 and SPI-19 regions, while P125109 does not.
Antimicrobial resistance markers were found in 39 isolates, all but one of which
belonged to Clade B. Phylogenetic analysis of the Queensland isolates in the
context of 170 international strains showed that Queensland Clade B isolates
group together with the previously identified global clade, while the other two
clades are distinct and appear largely restricted to Australia. Locally sourced
environmental isolates included in this analysis all belonged to Clades A and C,
which is consistent with the theory that these clades are a source of locally
acquired infection, while Clade B isolates are mostly travel related.
PMID- 29338019
TI - Survey of checkpoints along the pathway to diverse biomedical research faculty.
AB - There is a persistent shortage of underrepresented minority (URM) faculty who are
involved in basic biomedical research at medical schools. We examined the entire
training pathway of potential candidates to identify the points of greatest loss.
Using a range of recent national data sources, including the National Science
Foundation's Survey of Earned Doctorates and Survey of Doctoral Recipients, we
analyzed the demographics of the population of interest, specifically those from
URM backgrounds with an interest in biomedical sciences. We examined the URM
population from high school graduates through undergraduate, graduate, and
postdoctoral training as well as the URM population in basic science tenure track
faculty positions at medical schools. We find that URM and non-URM trainees are
equally likely to transition into doctoral programs, to receive their doctoral
degree, and to secure a postdoctoral position. However, the analysis reveals that
the diversions from developing a faculty career are found primarily at two
clearly identifiable places, specifically during undergraduate education and in
transition from postdoctoral fellowship to tenure track faculty in the basic
sciences at medical schools. We suggest focusing additional interventions on
these two stages along the educational pathway.
PMID- 29338018
TI - Oral mucosa tissue gene expression profiling before, during, and after radiation
therapy for tonsil squamous cell carcinoma.
AB - BACKGROUND: Radiation-therapy (RT) induces mucositis, a clinically challenging
condition with limited prophylactic interventions and no predictive tests. In
this pilot study, we applied global gene-expression analysis on serial human oral
mucosa tissue and blood cells from patients with tonsil squamous cell cancer
(TSCC) to identify genes involved in mucositis pathogenesis. METHODS AND
FINDINGS: Eight patients with TSCC each provided consecutive buccal biopsies and
blood cells before, after 7 days of RT treatment, and 20 days following RT. We
monitored clinical mucositis and performed gene-expression analysis on tissue
samples. We obtained control tissue from nine healthy individuals. After RT,
expression was upregulated in apoptosis inducer and inhibitor genes, EDA2R and
MDM2, and in POLH, a DNA-repair polymerase. Expression was downregulated in six
members of the histone cluster family, e.g., HIST1H3B. Gene expression related to
proliferation and differentiation was altered, including MKI67 (downregulated),
which encodes the Ki-67-proliferation marker, and KRT16 (upregulated), which
encodes keratin16. These alterations were not associated with the clinical
mucositis grade. However, the expression of LY6G6C, which encodes a surface
immunoregulatory protein, was upregulated before treatment in three cases of
clinical none/mild mucositis, but not in four cases of ulcerative mucositis.
CONCLUSION: RT caused molecular changes related to apoptosis, DNA-damage, DNA
repair, and proliferation without a correlation to the severity of clinical
mucositis. LY6G6C may be a potential protective biomarker for ulcerative
mucositis. Based on these results, our study model of consecutive human biopsies
will be useful in designing a prospective clinical validation trial to
characterize molecular mucositis and identify predictive biomarkers.
PMID- 29338020
TI - Autonomic stress reactivity and craving in individuals with problematic Internet
use.
AB - The link between autonomic stress reactivity and subjective urge/craving has been
less systematically examined in behavioral addictions (i.e. problematic Internet
use) than in substance use disorders. The present study investigated whether
problematic Internet users (PU) show enhanced autonomic stress reactivity than
non-PU, indexed by lower Heart Rate Variability (HRV) and higher Skin Conductance
Level (SCL) reactivity during the Trier Social Stress Test (TSST), whether
greater reactivity is related to stronger Internet craving, and whether
problematic Internet usage is associated with some dysfunctional psychological
features. Based on their Internet Addiction Test scores, participants were
divided into PU (N = 24) and non-PU (N = 21). Their heart rate and skin
conductance were continuously recorded during baseline, social stressors, and
recovery. Craving for Internet usage were collected using a Likert scale before
and after the TSST. The SDNN, an overall measure of HRV, was significantly lower
in PU than non-PU during baseline, but not during and after stressful task.
Furthermore, only among PU a significant negative correlation emerged between
SDNN during recovery and craving ratings after the test. No group differences
emerged for SCL. Lastly, PU endorsed more mood, obsessive-compulsive, and alcohol
related problems. Our findings suggest that problems in controlling one's use of
the Internet may be related to reduced autonomic balance at rest. Moreover, our
results provide new insights into the characterization of craving in PIU,
indicating the existence of a relationship between craving for Internet usage and
reduced autonomic flexibility.
PMID- 29338021
TI - Coral physiology and microbiome dynamics under combined warming and ocean
acidification.
AB - Rising seawater temperature and ocean acidification threaten the survival of
coral reefs. The relationship between coral physiology and its microbiome may
reveal why some corals are more resilient to these global change conditions.
Here, we conducted the first experiment to simultaneously investigate changes in
the coral microbiome and coral physiology in response to the dual stress of
elevated seawater temperature and ocean acidification expected by the end of this
century. Two species of corals, Acropora millepora containing the thermally
sensitive endosymbiont C21a and Turbinaria reniformis containing the thermally
tolerant endosymbiont Symbiodinium trenchi, were exposed to control (26.5 degrees
C and pCO2 of 364 MUatm) and treatment (29.0 degrees C and pCO2 of 750 MUatm)
conditions for 24 days, after which we measured the microbial community
composition. These microbial findings were interpreted within the context of
previously published physiological measurements from the exact same corals in
this study (calcification, organic carbon flux, ratio of photosynthesis to
respiration, photosystem II maximal efficiency, total lipids, soluble animal
protein, soluble animal carbohydrates, soluble algal protein, soluble algal
carbohydrate, biomass, endosymbiotic algal density, and chlorophyll a). Overall,
dually stressed A. millepora had reduced microbial diversity, experienced large
changes in microbial community composition, and experienced dramatic
physiological declines in calcification, photosystem II maximal efficiency, and
algal carbohydrates. In contrast, the dually stressed coral T. reniformis
experienced a stable and more diverse microbiome community with minimal
physiological decline, coupled with very high total energy reserves and
particulate organic carbon release rates. Thus, the microbiome changed and
microbial diversity decreased in the physiologically sensitive coral with the
thermally sensitive endosymbiotic algae but not in the physiologically tolerant
coral with the thermally tolerant endosymbiont. Our results confirm recent
findings that temperature-stress tolerant corals have a more stable microbiome,
and demonstrate for the first time that this is also the case under the dual
stresses of ocean warming and acidification. We propose that coral with a stable
microbiome are also more physiologically resilient and thus more likely to
persist in the future, and shape the coral species diversity of future reef
ecosystems.
PMID- 29338023
TI - Traditional agricultural practices and the sex ratio today.
AB - We study the historical origins of cross-country differences in the male-to
female sex ratio. Our analysis focuses on the use of the plough in traditional
agriculture. In societies that did not use the plough, women tended to
participate in agriculture as actively as men. By contrast, in societies that
used the plough, men specialized in agricultural work, due to the physical
strength needed to pull the plough or control the animal that pulls it. We
hypothesize that this difference caused plough-using societies to value boys more
than girls. Today, this belief is reflected in male-biased sex ratios, which
arise due to sex-selective abortion or infanticide, or gender-differences in
access to family resources, which results in higher mortality rates for girls.
Testing this hypothesis, we show that descendants of societies that traditionally
practiced plough agriculture today have higher average male-to-female sex ratios.
We find that this effect systematically increases in magnitude and statistical
significance as one looks at older cohorts. Estimates using instrumental
variables confirm our findings from multivariate OLS analysis.
PMID- 29338022
TI - Bone metabolism dynamics in the early post-transplant period following kidney and
liver transplantation.
AB - Bone disease contributes to relevant morbidity after solid organ transplantation.
Vitamin D has a crucial role for bone metabolism. Activation of vitamin D depends
on the endocrine function of both, liver and kidney. Our study assessed key
markers of bone metabolism at time of transplantation and 6 months after
transplantation among 70 kidney and 70 liver recipients. In 70 kidney recipients
25-OH vitamin D levels did not differ significantly between peri-transplant
(median 32.5nmol/l) and 6 months post-transplant (median 41.9nmol/l; P = 0.272).
Six months post-transplant median 1, 25-(OH)2 vitamin D levels increased by >300%
(from 9.1 to 36.5ng/l; P<0.001) and median intact parathyroid hormone levels
decreased by 68.4% (from 208.7 to 66.0 ng/l; P<0.001). Median beta-Crosslaps
(CTx) and total procollagen type 1 amino-terminal propeptide (P1NP) decreased by
65.1% (from 1.32 to 0.46ng/ml; P<0.001) and 60.6% (from 158.2 to 62.3ng/ml;
P<0.001), respectively. Kidney recipients with incident fractures had
significantly lower levels of 1, 25-(OH)2 vitamin D at time of transplantation
and of intact parathyroid hormone 6 months post-transplant. Among 70 liver
recipients, 25-OH vitamin D, 1, 25-(OH)2 vitamin D and intact parathyroid hormone
levels were not significantly altered between peri-transplant and 6 months post
transplant. Contrary to kidney recipients, median CTx increased by 60.0% (from
0.45 to 0.72 ng/ml; P = 0.002) and P1NP by 49.3% (from 84.0 to 125.4ng/ml; P =
0.001) in the longitudinal course. Assessed biomarkers didn't differ between
liver recipients with and without fractures. To conclude, the assessed panel of
biomarkers proved highly dynamic after liver as well as kidney transplantation in
the early post-transplant period. After kidney transplantation a significant gain
in 1, 25-(OH)2 vitamin D combined with a decline in iPTH, CTx and P1NP, whereas
after liver transplantation an increase in CTx and P1NP were characteristic.
PMID- 29338024
TI - Quantitative in vivo mapping of myocardial mitochondrial membrane potential.
AB - BACKGROUND: Mitochondrial membrane potential (DeltaPsim) arises from normal
function of the electron transport chain. Maintenance of DeltaPsim within a
narrow range is essential for mitochondrial function. Methods for in vivo
measurement of DeltaPsim do not exist. We use 18F-labeled tetraphenylphosphonium
(18F-TPP+) to measure and map the total membrane potential, DeltaPsiT, as the sum
of DeltaPsim and cellular (DeltaPsic) electrical potentials. METHODS: Eight pigs,
five controls and three with a scar-like injury, were studied. Pigs were studied
with a dynamic PET scanning protocol to measure 18F-TPP+ volume of distribution,
VT. Fractional extracellular space (fECS) was measured in 3 pigs. We derived
equations expressing DeltaPsiT as a function of VT and the volume-fractions of
mitochondria and fECS. Seventeen segment polar maps and parametric images of
DeltaPsiT were calculated in millivolts (mV). RESULTS: In controls, mean
segmental DeltaPsiT = -129.4+/-1.4 mV (SEM). In pigs with segmental tissue
injury, DeltaPsiT was clearly separated from control segments but variable, in
the range -100 to 0 mV. The quality of DeltaPsiT maps was excellent, with low
noise and good resolution. Measurements of DeltaPsiT in the left ventricle of
pigs agree with previous in in-vitro measurements. CONCLUSIONS: We have analyzed
the factors affecting the uptake of voltage sensing tracers and developed a
minimally invasive method for mapping DeltaPsiT in left ventricular myocardium of
pigs. DeltaPsiT is computed in absolute units, allowing for visual and
statistical comparison of individual values with normative data. These studies
demonstrate the first in vivo application of quantitative mapping of total tissue
membrane potential, DeltaPsiT.
PMID- 29338025
TI - Adolescent cohorts assessing growth, cardiovascular and cognitive outcomes in low
and middle-income countries.
AB - INTRODUCTION: Life-course studies are needed to explore how exposures during
adolescence, particularly puberty, contribute to later cardiovascular risk and
cognitive health in low and middle-income countries (LMIC), where 90% of the
world's young people live. The extent of any existing cohorts investigating these
outcomes in LMIC has not previously been described. METHODS: We performed a
systematic literature review to identify population cohort studies of adolescents
in LMIC that assessed anthropometry and any of cardiovascular risk (blood
pressure, physical activity, plasma glucose/lipid profile and substance misuse),
puberty (age at menarche, Tanner staging, or other form of pubertal staging) or
cognitive outcomes. Studies that recruited participants on the basis of a pre
existing condition or involved less than 500 young people were excluded.
FINDINGS: 1829 studies were identified, and 24 cohorts fulfilled inclusion
criteria based in Asia (10), Africa (6) and South / Central America (8). 14 (58%)
of cohorts identified were based in one of four countries; India, Brazil, Vietnam
or Ethiopia. Only 2 cohorts included a comprehensive cardiovascular assessment,
tanner pubertal staging, and cognitive outcomes. CONCLUSION: Improved utilisation
of existing datasets and additional cohort studies of adolescents in LMIC that
collect contemporaneous measures of growth, cognition, cardiovascular risk and
pubertal development are needed to better understand how this period of the life
course influences future non-communicable disease morbidity and cognitive
outcomes.
PMID- 29338026
TI - Flow cytometric analysis identifies changes in S and M phases as novel cell cycle
alterations induced by the splicing inhibitor isoginkgetin.
AB - The spliceosome is a large ribonucleoprotein complex that catalyzes the removal
of introns from RNA polymerase II-transcribed RNAs. Spliceosome assembly occurs
in a stepwise manner through specific intermediates referred to as pre
spliceosome complexes E, A, B, B* and C. It has been reported that small molecule
inhibitors of the spliceosome that target the SF3B1 protein component of complex
A lead to the accumulation of cells in the G1 and G2/M phases of the cell cycle.
Here we performed a comprehensive flow cytometry analysis of the effects of
isoginkgetin (IGG), a natural compound that interferes with spliceosome assembly
at a later step, complex B formation. We found that IGG slowed cell cycle
progression in multiple phases of the cell cycle (G1, S and G2) but not M phase.
This pattern was somewhat similar to but distinguishable from changes associated
with an SF3B1 inhibitor, pladienolide B (PB). Both drugs led to a significant
decrease in nascent DNA synthesis in S phase, indicative of an S phase arrest.
However, IGG led to a much more prominent S phase arrest than PB while PB
exhibited a more pronounced G1 arrest that decreased the proportion of cells in S
phase as well. We also found that both drugs led to a comparable decrease in the
proportion of cells in M phase. This work indicates that spliceosome inhibitors
affect multiple phases of the cell cycle and that some of these effects vary in
an agent-specific manner despite the fact that they target splicing at similar
stages of spliceosome assembly.
PMID- 29338027
TI - Distribution of cone density, spacing and arrangement in adult healthy retinas
with adaptive optics flood illumination.
AB - The aim of this article is to analyse cone density, spacing and arrangement using
an adaptive optics flood illumination retina camera (rtx1TM) on a healthy
population. Cone density, cone spacing and packing arrangements were measured on
the right retinas of 109 subjects at 2 degrees , 3 degrees , 4 degrees , 5
degrees and 6 degrees of eccentricity along 4 meridians. The effects of
eccentricity, meridian, axial length, spherical equivalent, gender and age were
evaluated. Cone density decreased on average from 28 884 +/- 3 692 cones/mm2, at
2 degrees of eccentricity, to 15 843 +/- 1 598 cones/mm2 at 6 degrees . A strong
inter-individual variation, especially at 2 degrees , was observed. No important
difference of cone density was observed between the nasal and temporal meridians
or between the superior and inferior meridians. However, the horizontal and
vertical meridians differed by around 14% (T-test, p<0.0001). Cone density,
expressed in units of area, decreased as a function of axial length (r2 = 0.60),
but remained constant (r2 = 0.05) when cone density is expressed in terms of
visual angle supporting the hypothesis that the retina is stretched during the
elongation of the eyeball. Gender did not modify the cone distribution. Cone
density was slightly modified by age but only at 2 degrees . The older group
showed a smaller density (7%). Cone spacing increased from 6,49 +/- 0,42 MUm to
8,72 +/- 0,45 MUm respectively between 2 degrees and 6 degrees of eccentricity.
The mosaic of the retina is mainly triangularly arranged (i.e. cells with 5 to 7
neighbors) from 2 degrees to 6 degrees . Around half of the cells had 6
neighbors.
PMID- 29338028
TI - Does providing more services increase the primary hospitals' revenue? An
assessment of national essential medicine policy based on 2,675 counties in
China.
AB - OBJECTIVE: To understand whether the increased outpatient service provision (OSP)
brings in enough additional income (excluding income from essential medicine) for
primary hospitals (INCOME) to compensate for reduced costs of medicine. METHODS:
The two outcomes, annual OSP and INCOME for the period of 2008-2012, were
collected from 34,506 primary hospitals in 2,675 counties in 31 provinces in
China by the national surveillance system. The data had a four-level hierarchical
structure; time points were nested within primary hospital, hospitals within
county, and counties within province. We fitted bivariate five-level random
effects regression models to examine correlations between OSP and INCOME in terms
of their mean values and dose-response effects of the essential medicine policy
(EMP). We adjusted for the effects of time period and selected hospital
resources. FINDINGS: The estimated correlation coefficients between the two
outcomes' mean values were strongly positive among provinces (r = 0.910),
moderately positive among counties (r = 0.380), and none among hospitals (r =
0.002) and time (r = 0.007). The correlation between their policy effects was
weakly positive among provinces (r = 0.234), but none at the county and hospital
levels. However, there were markedly negative correlation coefficients between
the mean and policy effects at -0.328 for OSP and -0.541 for INCOME at the
hospital level. CONCLUSION: There was no evidence to suggest an association
between the two outcomes in terms of their mean values and dose-response effects
of EMP at the hospital level. This indicated that increased OSP did not bring
enough additional INCOME. Sustainable mechanisms to compensate primary hospitals
are needed.
PMID- 29338029
TI - Implicit learning deficit in children with Duchenne muscular dystrophy: Evidence
for a cerebellar cognitive impairment?
AB - This study aimed at comparing implicit sequence learning in individuals affected
by Duchenne Muscular Dystrophy without intellectual disability and age-matched
typically developing children. A modified version of the Serial Reaction Time
task was administered to 32 Duchenne children and 37 controls of comparable
chronological age. The Duchenne group showed a reduced rate of implicit learning
even if in the absence of global intellectual disability. This finding provides
further evidence of the involvement of specific aspects of cognitive function in
Duchenne muscular dystrophy and on its possible neurobiological substrate.
PMID- 29338030
TI - Incidence, microbiology, and outcomes of endophthalmitis after 111,876 pars plana
vitrectomies at a single, tertiary eye care hospital.
AB - PURPOSE: To describe the incidence, risk factors, clinical presentation,
causative organisms, and outcomes in patients with endophthalmitis following pars
plana vitrectomy (20G and minimally invasive vitrectomy surgery (MIVS). METHODS:
Of 111,876 vitrectomies (70,585 20-G 41,291 MIVS) performed, 45 cases developed
acute-onset, postoperative endophthalmitis. RESULTS: The rate of culture positive
and culture negative endophthalmitis was 0.021% (2.1/10,000 surgeries) and 0.019%
(1.9/10,000 surgeries) overall, 0.031% (3.1/10,000 surgeries) and 0.025%
(2.5/10,000 surgeries) in 20G, and 0.005% (0.5/10,000 surgeries) and 0.007%
(0.7/10,000 surgeries) in the MIVS group respectively. Potential predisposing
factors were as follows: diabetes, 46.7%; vitrectomy for vascular retinopathies,
44.4%; and vitrectomy combined with anterior segment surgeries, 35.5%. The
culture proven rates were 53.3% overall, 55.0% for 20G and 40.0% for MIVS. The
most common organism was Pseudomonas aeruginosa for 20G. Klebsiella and
Staphylococcus aureus were isolated in the two culture positive cases in MIVS
group. The follow-up period for the patients with endophthalmitis was 586.14 +/-
825.15 days. Seven were lost to follow up beyond one week. Of the remaining 38,
13 (34.2%) cases had a favorable visual outcome (i.e., best-corrected visual
acuity [BCVA] > 5/200) and 24 (63.2%) had unfavorable visual outcome (BCVA <
5/200). Group with culture test results negative had significantly better
outcomes (P < 0.05) as compared to those with positive. CONCLUSIONS: MIVS does
not increase the risk of endophthalmitis. Outcomes are poor despite appropriate
treatment, particularly in cases with culture results positive.
PMID- 29338031
TI - Pre-existing malignancy results in increased prevalence of distinct populations
of CD4+ T cells during sepsis.
AB - The presence of pre-existing malignancy in murine hosts results in increased
immune dysregulation and risk of mortality following a septic insult. Based on
the known systemic immunologic changes that occur in cancer hosts, we
hypothesized that the presence of pre-existing malignancy would result in
phenotypic and functional changes in CD4+ T cell responses following sepsis. In
order to conduct a non-biased, unsupervised analysis of phenotypic differences
between CD4+ T cell compartments, cohorts of mice were injected with LLC1 tumor
cells and tumors were allowed to grow for 3 weeks. These cancer hosts and age
matched non-cancer controls were then subjected to CLP. Splenocytes were
harvested at 24h post CLP and flow cytometry and SPADE (Spanning-tree Progression
Analysis of Density-normalized Events) were used to analyze populations of CD4+
cells most different between the two groups. Results indicated that relative to
non-cancer controls, cancer mice contained more resting memory CD4+ T cells, more
activated CD4+ effectors, and fewer naive CD4+ T cells during sepsis, suggesting
that the CD4+ T cell compartment in cancer septic hosts is one of increased
activation and differentiation. Moreover, cancer septic animals exhibited
expansion of two distinct subsets of CD4+ T cells relative to previously healthy
septic controls. Specifically, we identified increases in both a PD-1hi
population and a distinct 2B4hi BTLAhi LAG-3hi population in cancer septic
animals. By combining phenotypic analysis of exhaustion markers with functional
analysis of cytokine production, we found that PD-1+ CD4+ cells in cancer hosts
failed to make any cytokines following CLP, while the 2B4+ PD-1lo cells in cancer
mice secreted increased TNF during sepsis. In sum, the immunophenotypic landscape
of cancer septic animals is characterized by both increased CD4+ T cell
activation and exhaustion, findings that may underlie the observed increased
mortality in mice with pre-existing malignancy following sepsis.
PMID- 29338032
TI - Perceptions of healthcare quality in Ghana: Does health insurance status matter?
AB - This study's objective is to provide an alternative explanation for the low
enrolment in health insurance in Ghana by analysing differences in perceptions
between the insured and uninsured of the non-technical quality of healthcare. It
further explores the association between insurance status and perception of
healthcare quality to ascertain whether insurance status matters in the
perception of healthcare quality. Data from a survey of 1,903 households living
in the catchment area of 64 health centres were used for the analysis. Two sample
independent t-tests were employed to compare the average perceptions of the
insured and uninsured on seven indicators of non-technical quality of healthcare.
A generalised ordered logit regression, controlling for socio-economic
characteristics and clustering at the health facility level, tested the
association between insurance status and perceived quality of healthcare. The
perceptions of the insured were found to be significantly more negative than the
uninsured and those of the previously insured were significantly more negative
than the never insured. Being insured was associated with a significantly lower
perception of healthcare quality. Thus, once people are insured, they tend to
perceive the quality of healthcare they receive as poor compared to those without
insurance. This study demonstrated that health insurance status matters in the
perceptions of healthcare quality. The findings also imply that perceptions of
healthcare quality may be shaped by individual experiences at the health
facilities, where the insured and uninsured may be treated differently. Health
insurance then becomes less attractive due to the poor perception of the
healthcare quality provided to individuals with insurance, resulting in low
demand for health insurance in Ghana. Policy makers in Ghana should consider
redesigning, reorganizing, and reengineering the National Healthcare Insurance
Scheme to ensure the provision of better quality healthcare for both the insured
and uninsured.
PMID- 29338035
TI - Genome wide identification of wheat and Brachypodium type one protein
phosphatases and functional characterization of durum wheat TdPP1a.
AB - Reversible phosphorylation is an essential mechanism regulating signal
transduction during development and environmental stress responses. An important
number of dephosphorylation events in the cell are catalyzed by type one protein
phosphatases (PP1), which catalytic activity is driven by the binding of
regulatory proteins that control their substrate specificity or subcellular
localization. Plants harbor several PP1 isoforms accounting for large functional
redundancies. While animal PP1s were reported to play relevant roles in
controlling multiple cellular processes, plant orthologs remain poorly studied.
To decipher the role of plant PP1s, we compared PP1 genes from three monocot
species, Brachypodium, common wheat and rice at the genomic and transcriptomic
levels. To gain more insight into the wheat PP1 proteins, we identified and
characterized TdPP1a, the first wheat type one protein phosphatase from a
Tunisian durum wheat variety Oum Rabiaa3. TdPP1a is highly conserved in sequence
and structure when compared to mammalian, yeast and other plant PP1s. We
demonstrate that TdPP1a is an active, metallo-dependent phosphatase in vitro and
is able to interact with AtI2, a typical regulator of PP1 functions. Also, TdPP1a
is capable to complement the heat stress sensitivity of the yeast mutant
indicating that TdPP1a is functional also in vivo. Moreover, transient expression
of TdPP1a::GFP in tobacco leaves revealed that it is ubiquitously distributed
within the cell, with a strong accumulation in the nucleus. Finally,
transcriptional analyses showed similar expression levels in roots and leaves of
durum wheat seedlings. Interestingly, the expression in leaves is significantly
induced following salinity stress, suggesting a potential role of TdPP1a in wheat
salt stress response.
PMID- 29338034
TI - Clonal growth strategy, diversity and structure: A spatiotemporal response to
sedimentation in tropical Cyperus papyrus swamps.
AB - Land degradation and soil erosion in the upper catchments of tropical lakes
fringed by papyrus vegetation can result in a sediment load gradient from land to
lakeward. Understanding the dynamics of clonal modules (ramets and genets) and
growth strategies of plants on such a gradient in both space and time is critical
for exploring a species adaptation and processes regulating population structure
and differentiation. We assessed the spatial and temporal dynamics in clonal
growth, diversity, and structure of an emergent macrophyte, Cyperus papyrus
(papyrus), in response to two contrasting sedimentation regimes by combining
morphological traits and genotype data using 20 microsatellite markers. A total
of 636 ramets from six permanent plots (18 x 30 m) in three Ethiopian papyrus
swamps, each with discrete sedimentation regimes (high vs. low) were sampled for
two years. We found that ramets under the high sedimentation regime (HSR) were
significantly clumped and denser than the sparse and spreading ramets under the
low sedimentation regime (LSR). The HSR resulted in significantly different
ramets with short culm height and girth diameter as compared to the LSR. These
results indicated that C. papyrus ameliorates the effect of sedimentation by
shifting clonal growth strategy from guerrilla (in LSR) to phalanx (in HSR).
Clonal richness, size, dominance, and clonal subrange differed significantly
between sediment regimes and studied time periods. Each swamp under HSR revealed
a significantly high clonal richness (R = 0.80) as compared to the LSR (R =
0.48). Such discrepancy in clonal richness reflected the occurrence of initial
and repeated seedling recruitment strategies as a response to different
sedimentation regimes. Overall, our spatial and short-term temporal observations
highlighted that HSR enhances clonal richness and decreases clonal subrange owing
to repeated seedling recruitment and genets turnover.
PMID- 29338033
TI - Intermittent, low dose carbon monoxide exposure enhances survival and
dopaminergic differentiation of human neural stem cells.
AB - Exploratory studies using human fetal tissue have suggested that intrastriatal
transplantation of dopaminergic neurons may become a future treatment for
patients with Parkinson's disease. However, the use of human fetal tissue is
compromised by ethical, regulatory and practical concerns. Human stem cells
constitute an alternative source of cells for transplantation in Parkinson's
disease, but efficient protocols for controlled dopaminergic differentiation need
to be developed. Short-term, low-level carbon monoxide (CO) exposure has been
shown to affect signaling in several tissues, resulting in both protection and
generation of reactive oxygen species. The present study investigated the effect
of CO produced by a novel CO-releasing molecule on dopaminergic differentiation
of human neural stem cells. Short-term exposure to 25 ppm CO at days 0 and 4
significantly increased the relative content of beta-tubulin III-immunoreactive
immature neurons and tyrosine hydroxylase expressing catecholaminergic neurons,
as assessed 6 days after differentiation. Also the number of microtubule
associated protein 2-positive mature neurons had increased significantly.
Moreover, the content of apoptotic cells (Caspase3) was reduced, whereas the
expression of a cell proliferation marker (Ki67) was left unchanged. Increased
expression of hypoxia inducible factor-1alpha and production of reactive oxygen
species (ROS) in cultures exposed to CO may suggest a mechanism involving
mitochondrial alterations and generation of ROS. In conclusion, the present
procedure using controlled, short-term CO exposure allows efficient dopaminergic
differentiation of human neural stem cells at low cost and may as such be useful
for derivation of cells for experimental studies and future development of donor
cells for transplantation in Parkinson's disease.
PMID- 29338036
TI - Static magnetic field enhances the anticancer efficacy of capsaicin on HepG2
cells via capsaicin receptor TRPV1.
AB - Static magnetic field (SMF) has shown some possibilities for cancer therapies. In
particular, the combinational effect between SMF and anti-cancer drugs has drawn
scientists' attentions in recent years. However, the underlying mechanism for the
drug-specific synergistic effect is far from being understood. Besides, the drugs
used are all conventional chemotherapy drugs, which may cause unpleasant side
effects. In this study, our results demonstrate for the first time that SMF could
enhance the anti-cancer effect of natural compound, capsaicin, on HepG2 cancer
cells through the mitochondria-dependent apoptosis pathway. We found that the
synergistic effect could be due to that SMF increased the binding efficiency of
capsaicin for the TRPV1 channel. These findings may provide a support to develop
an application of SMF for cancer therapy. The present study offers the first
trial in combining SMF with natural compound on anti-cancer treatment, which
provides additional insight into the interaction between SMF and anti-cancer
drugs and opens the door for the development of new strategies in fighting cancer
with minimum cytotoxicity and side effects.
PMID- 29338037
TI - Stentless vs. stented bioprosthesis for aortic valve replacement: A case matched
comparison of long-term follow-up and subgroup analysis of patients with native
valve endocarditis.
AB - BACKGROUND: Current retrospective evidence suggests similar clinical and superior
hemodynamic outcomes of the Sorin Freedom Solo stentless aortic valve (SFS)
(LivaNova PLC, London, UK) compared to the Carpentier Edwards Perimount stented
aortic valve (CEP) (Edwards Lifesciences Inc., Irvine, California, USA). To date,
no reports exist describing case-matched long-term outcomes and analysis for
treatment of native valve endocarditis (NVE). METHODS: From 2004 through 2014, 77
consecutive patients (study group, 59.7% male, 68.9 +/- 12.5 years, logEuroSCORE
II 7.6 +/- 12.3%) received surgical aortic valve replacement (SAVR) with the SFS.
A control group of patients after SAVR with the CEP was retrieved from our
database and matched to the study group regarding 15 parameters including
preoperative endocarditis. Acute perioperative outcomes and follow-up data (mean
follow-up time 48.7+/-29.8 months, 95% complete) were retrospectively analyzed.
RESULTS: No differences in early mortality occurred during 30-day follow up
(3/77; 3.9% vs. 4/77; 5.2%; p = 0.699). Echocardiographic findings revealed lower
postprocedural transvalvular pressure gradients (max. 17.0 +/- 8.2 vs. 24.5 +/-
9.2 mmHg, p< 0.001/ mean pressure of 8.4 +/- 4.1 vs. 13.1 +/- 5.9 mmHg, p< 0.001)
in the SFS group. Structural valve degeneration (SVD) (5.2% vs. 0%; p = 0.04) and
valve explantation due to SVD or prosthetic valve endocarditis (PVE) (9.1% vs.
1.3%; p = 0.04) was more frequent in the SFS group. All-cause mortality during
follow-up was 20.8% vs. 14.3% (p = 0.397). When patients were divided into
subgroups of NVE and respective utilized bioprosthesis, the SFS presented
impaired outcomes regarding mortality in NVE cases (p = 0.031). CONCLUSIONS: The
hemodynamic superiority of the SFS was confirmed in this comparison. However,
clinical outcomes in terms of SVD and PVE rates, as well as survival after NVE,
were inferior in this study. Therefore, we are reluctant to recommend utilization
of the SFS for treatment of NVE.
PMID- 29338038
TI - Does the leading pharmaceutical reform in China really solve the issue of overly
expensive healthcare services? Evidence from an empirical study.
AB - BACKGROUND: Healthcare system reform of Sanming city has become a leading
healthcare reform model in China. It has developed a rigorous pharmaceutical
reform consisted of the Zero Mark-up Drug Policy and the Centralized Procurement
of Medicine Policy to bring down drug expenses and total health expenditures.
However, despite the credit and much attention have been given to Sanming's
pharmaceutical reform, its impact still remains unclear. Therefore, the purpose
of this study was to explore the impact of the pharmaceutical reform of Sanming
on both drug and total health expenditures. METHODS: Interrupted time series
analysis with three segments divided by two intervention points was employed to
evaluate the impact of the pharmaceutical reform. Segment 1 was the pre-reform
period which captured the baseline information. Segment 2 occurred after the
first intervention point when the Zero Mark-up Drug Policy was implemented,
whereas Segment 3 was after the implementation of the Centralized Procurement of
Medicine Policy. Primary outcomes are outpatient drug expenditure, outpatient
total health expenditure, inpatient drug expenditure, and inpatient total health
expenditure. Data spanning from May 2012 to May 2014 are included. RESULTS: Both
drug and total health expenditures exhibited rising trends before any policy was
carried out. The launch of Zero Mark-up Drug Policy led to significant instant
reductions in levels of outpatient drug expenditure (coefficient = -6,602.99,
p<0.01), outpatient total health expenditure (coefficient = -9,958.58, p<0.05),
inpatient drug expenditure (coefficient = -7,520.90, p<0.01), and inpatient total
health expenditure (coefficient = -16,737, p<0.01). Moreover, the previous upward
trends were changed into downward trends for inpatient drug expenditure
(coefficient = -2,747.02, p = 0.00) and total health expenditure (coefficient =
3,069.29, p = 0.12). However, after the implementation of Centralized Procurement
of Medicine Policy, we observed no significant instant level changes and also,
the inpatient drug expenditure (coefficient = 372.95, p = 0.01) and total health
expenditure (coefficient = 788.76, p = 0.06) resumed upward trends again.
CONCLUSIONS: Although the pharmaceutical reform could control or reduced drug
expenditure and total health expenditure in short term, expenditures gradually
resumed growing again and reached or even exceeded their baseline levels of pre
reform period, indicating the effect became weakened or even faded out in long
term. In all, the pharmaceutical reform as a whole failed to meet its goal of
combating sharp growth of drug and total health expenditure.
PMID- 29338039
TI - STAT3 expression by myeloid cells is detrimental for the T- cell-mediated control
of infection with Mycobacterium tuberculosis.
AB - STAT3 is a master regulator of the immune responses. Here we show that M.
tuberculosis-infected stat3fl/fl lysm cre mice, defective for STAT3 in myeloid
cells, contained lower bacterial load in lungs and spleens, reduced granuloma
extension but higher levels of pulmonary neutrophils. STAT3-deficient macrophages
showed no improved control of intracellular mycobacterial growth. Instead,
protection associated to elevated ability of stat3fl/fl lysm cre antigen
presenting cells (APCs) to release IL-6 and IL-23 and to stimulate IL-17
secretion by mycobacteria-specific T cells. The increased IL-17 secretion
accounted for the improved control of infection since neutralization of IL-17
receptor A in stat3fl/fl lysm cre mice hampered bacterial control. APCs lacking
SOCS3, which inhibits STAT3 activation via several cytokine receptors, were poor
inducers of priming and of the IL-17 production by mycobacteria-specific T cells.
In agreement, socs3fl/fl cd11c cre mice deficient of SOCS3 in DCs showed
increased susceptibility to M. tuberculosis infection. While STAT3 in APCs
hampered IL-17 responses, STAT3 in mycobacteria-specific T cells was critical for
IL-17 secretion, while SOCS3 in T cells impeded IL-17 secretion. Altogether,
STAT3 signalling in myeloid cells is deleterious in the control of infection with
M. tuberculosis.
PMID- 29338040
TI - Identification and expression analyses of WRKY genes reveal their involvement in
growth and abiotic stress response in watermelon (Citrullus lanatus).
AB - Despite identification of WRKY family genes in numerous plant species, a little
is known about WRKY genes in watermelon, one of the most economically important
fruit crops around the world. Here, we identified a total of 63 putative WRKY
genes in watermelon and classified them into three major groups (I-III) and five
subgroups (IIa-IIe) in group II. The structure analysis indicated that ClWRKYs
with different WRKY domains or motifs may play different roles by regulating
respective target genes. The expressions of ClWRKYs in different tissues indicate
that they are involved in various tissue growth and development. Furthermore, the
diverse responses of ClWRKYs to drought, salt, or cold stress suggest that they
positively or negatively affect plant tolerance to various abiotic stresses. In
addition, the altered expression patterns of ClWRKYs in response to phytohormones
such as, ABA, SA, MeJA, and ETH, imply the occurrence of complex cross-talks
between ClWRKYs and plant hormone signals in regulating plant physiological and
biological processes. Taken together, our findings provide valuable clues to
further explore the function and regulatory mechanisms of ClWRKY genes in
watermelon growth, development, and adaption to environmental stresses.
PMID- 29338041
TI - Cadherins in the retinal pigment epithelium (RPE) revisited: P-cadherin is the
highly dominant cadherin expressed in human and mouse RPE in vivo.
AB - The retinal pigment epithelium (RPE) supports the health and function of retinal
photoreceptors and is essential for normal vision. RPE cells are post-mitotic,
terminally differentiated, and polarized epithelial cells. In pathological
conditions, however, they lose their epithelial integrity, become dysfunctional,
even dedifferentiate, and ultimately die. The integrity of epithelial cells is
maintained, in part, by adherens junctions, which are composed of cadherin
homodimers and p120-, beta-, and alpha-catenins linking to actin filaments. While
E-cadherin is the major cadherin for forming the epithelial phenotype in most
epithelial cell types, it has been reported that cadherin expression in RPE cells
is different from other epithelial cells based on results with cultured RPE
cells. In this study, we revisited the expression of cadherins in the RPE to
clarify their relative contribution by measuring the absolute quantity of cDNAs
produced from mRNAs of three classical cadherins (E-, N-, and P-cadherins) in the
RPE in vivo. We found that P-cadherin (CDH3) is highly dominant in both mouse and
human RPE in situ. The degree of dominance of P-cadherin is surprisingly large,
with mouse Cdh3 and human CDH3 accounting for 82-85% and 92-93% of the total of
the three cadherin mRNAs, respectively. We confirmed the expression of P-cadherin
protein at the cell-cell border of mouse RPE in situ by immunofluorescence.
Furthermore, we found that oxidative stress induces dissociation of P-cadherin
and beta-catenin from the cell membrane and subsequent translocation of beta
catenin into the nucleus, resulting in activation of the canonical Wnt/beta
catenin pathway. This is the first report of absolute comparison of the
expression of three cadherins in the RPE, and the results suggest that the
physiological role of P-cadherin in the RPE needs to be reevaluated.
PMID- 29338042
TI - A pharmacological screen for compounds that rescue the developmental lethality of
a Drosophila ATM mutant.
AB - Ataxia-telangiectasia (A-T) is a neurodegenerative disease caused by mutation of
the A-T mutated (ATM) gene. ATM encodes a protein kinase that is activated by DNA
damage and phosphorylates many proteins, including those involved in DNA repair,
cell cycle control, and apoptosis. Characteristic biological and molecular
functions of ATM observed in mammals are conserved in Drosophila melanogaster. As
an example, conditional loss-of-function ATM alleles in flies cause progressive
neurodegeneration through activation of the innate immune response. However,
unlike in mammals, null alleles of ATM in flies cause lethality during
development. With the goals of understanding biological and molecular roles of
ATM in a whole animal and identifying candidate therapeutics for A-T, we
performed a screen of 2400 compounds, including FDA-approved drugs, natural
products, and bioactive compounds, for modifiers of the developmental lethality
caused by a temperature-sensitive ATM allele (ATM8) that has reduced kinase
activity at non-permissive temperatures. Ten compounds reproducibly suppressed
the developmental lethality of ATM8 flies, including Ronnel, which is an
organophosphate. Ronnel and other suppressor compounds are known to cause
mitochondrial dysfunction or to inhibit the enzyme acetylcholinesterase, which
controls the levels of the neurotransmitter acetylcholine, suggesting that
detrimental consequences of reduced ATM kinase activity can be rescued by
inhibiting the function of mitochondria or increasing acetylcholine levels. We
carried out further studies of Ronnel because, unlike the other compounds that
suppressed the developmental lethality of homozygous ATM8 flies, Ronnel was toxic
to the development of heterozygous ATM8 flies. Ronnel did not affect the innate
immune response of ATM8 flies, and it further increased the already high levels
of DNA damage in brains of ATM8 flies, but its effects were not harmful to the
lifespan of rescued ATM8 flies. These results provide new leads for understanding
the biological and molecular roles of ATM and for the treatment of A-T.
PMID- 29338043
TI - Search for independent (beta/alpha)4 subdomains in a (beta/alpha)8 barrel beta
glucosidase.
AB - Proteins that fold as (beta/alpha)8 barrels are thought to have evolved from half
barrels that underwent duplication and fusion events. The evidence is
particularly clear for small barrels, which have almost identical halves.
Additionally, computational calculations of the thermodynamic stability of these
structures in the presence of denaturants have revealed that (beta/alpha)8
barrels contain two subunits or domains corresponding to half-barrels. Hence,
within (beta/alpha)8 barrels, half-barrels are self-contained units. Here, we
tested this hypothesis using beta-glucosidase from the bacterium Thermotoga
maritima (bglTm), which has a (beta/alpha)8 barrel structure. Mutations were
introduced to disrupt the noncovalent contacts between its halves and reveal the
presence of two domains within bglTm, thus resulting in the creation of mutants
T1 (containing W12A and I217A mutations) and T2 (containing W12A, H195A, I217A
and F404A mutations). Mutants T1 and T2 were properly folded, as indicated by
their fluorescence spectra and enzyme kinetic parameters. T1 and wild-type bglTm
were equally stable, as shown by the results of thermal inactivation,
differential scanning fluorimetry and guanidine hydrochloride denaturation
experiments. However, T2 showed a first-order inactivation at 80 degrees C, a
single melting temperature of 82 degrees C and only one transition concentration
(c50) in 2.4 M guanidine hydrochloride. Additionally, T1 and T2 exhibited a
cooperative denaturation process that followed a two-state model (m-values equal
to 1.4 and 1.6 kcal/mol/M, respectively), similar to that of wild-type bglTm (1.2
kcal/mol/M). Hence, T1 and T2 each denatured as a single unit, although they
contained different degrees of disruption between their halves. In conclusion,
bglTm halves are equivalent in terms of their thermal and chemical stability;
thus, their separate contributions to (beta/alpha)8 barrel unfolding cannot be
disentangled.
PMID- 29338046
TI - Correction: Women's health in the occupied Palestinian territories: Contextual
influences on subjective and objective health measures.
AB - [This corrects the article DOI: 10.1371/journal.pone.0186610.].
PMID- 29338044
TI - Probing the changes in gene expression due to alpha-crystallin mutations in mouse
models of hereditary human cataract.
AB - The mammalian eye lens expresses a high concentration of crystallins (alpha, beta
and gamma-crystallins) to maintain the refractive index essential for lens
transparency. Crystallins are long-lived proteins that do not turnover throughout
life. The structural destabilization of crystallins by UV exposure, glycation,
oxidative stress and mutations in crystallin genes leads to protein aggregation
and development of cataracts. Several destabilizing mutations in crystallin genes
are linked with human autosomal dominant hereditary cataracts. To investigate the
mechanism by which the alpha-crystallin mutations Cryaa-R49C and Cryab-R120G lead
to cataract formation, we determined whether these mutations cause an altered
expression of specific transcripts in the lens at an early postnatal age by RNA
seq analysis. Using knock-in mouse models previously generated in our laboratory,
in the present work, we identified genes that exhibited altered abundance in the
mutant lenses, including decreased transcripts for Clic5, an intracellular water
channel in Cryaa-R49C heterozygous mutant lenses, and increased transcripts for
Eno1b in Cryab-R120G heterozygous mutant lenses. In addition, RNA-seq analysis
revealed increased histones H2B, H2A, and H4 gene expression in Cryaa-R49C mutant
lenses, suggesting that the alphaA-crystallin mutation regulates histone
expression via a transcriptional mechanism. Additionally, these studies confirmed
the increased expression of histones H2B, H2A, and H4 by proteomic analysis of
Cryaa-R49C knock-in and Cryaa;Cryab gene knockout lenses reported previously.
Taken together, these findings offer additional insight into the early
transcriptional changes caused by Cryaa and Cryab mutations associated with
autosomal dominant human cataracts, and indicate that the transcript levels of
certain genes are affected by the expression of mutant alpha-crystallin in vivo.
PMID- 29338045
TI - Protection induced by virus-like particle vaccine containing tandem repeat gene
of respiratory syncytial virus G protein.
AB - Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract
illness in infants, young children and the elderly. However, there is no licensed
vaccine available against RSV infection. In this study, we generated virus-like
particle (VLP) vaccine and investigated the vaccine efficacy in a mouse model.
For VLP vaccines, tandem gene (1-780 bp) for V1 VLPs and tandem repeat gene
(repeated 450-780 bp) for V5 VLPs were constructed in pFastBacTM vectors,
respectively. Influenza matrix protein 1 (M1) was used as a core protein in the
VLPs. Notably, upon challenge infection, significantly lower virus loads were
measured in the lung of mice immunized with V1 or V5 VLPs compared to those of
naive mice and formalin-inactivated RSV immunized control mice. In particular, V5
VLPs immunization showed significantly lower virus titers than V1 VLPs
immunization. Furthermore, V5 VLPs immunization elicited increased memory B cells
responses in the spleen. These results indicated that V5 VLP vaccine containing
tandem repeat gene protein provided better protection than V1 VLPs with
significantly decreased inflammation in the lungs. Thus, V5 VLPs could be a
potential vaccine candidate against RSV.
PMID- 29338047
TI - Amino acid substitutions affecting aspartic acid 605 and valine 606 decrease the
interaction strength between the influenza virus RNA polymerase PB2 '627' domain
and the viral nucleoprotein.
AB - The influenza virus RNA genome is transcribed and replicated in the context of
the viral ribonucleoprotein (vRNP) complex by the viral RNA polymerase. The
nucleoprotein (NP) is the structural component of the vRNP providing a scaffold
for the viral RNA. In the vRNP as well as during transcription and replication
the viral polymerase interacts with NP but it is unclear which parts of the
polymerase and NP mediate these interactions. Previously the C-terminal '627'
domain (amino acids 538-693) of PB2 was shown to interact with NP. Here we report
that a fragment encompassing amino acids 146-185 of NP is sufficient to mediate
this interaction. Using NMR chemical shift perturbation assays we show that amino
acid region 601 to 607 of the PB2 '627' domain interacts with this fragment of
NP. Substitutions of these PB2 amino acids resulted in diminished RNP activity
and surface plasmon resonance assays showed that amino acids D605 was essential
for the interaction with NP and V606 may also play a partial role in the
interaction. Collectively these results reveal a possible interaction surface
between NP and the PB2 subunit of the RNA polymerase complex.
PMID- 29338048
TI - Ebola virus requires a host scramblase for externalization of phosphatidylserine
on the surface of viral particles.
AB - Cell surface receptors for phosphatidylserine contribute to the entry of Ebola
virus (EBOV) particles, indicating that the presence of phosphatidylserine in the
envelope of EBOV is important for the internalization of EBOV particles.
Phosphatidylserine is typically distributed in the inner layer of the plasma
membrane in normal cells. Progeny virions bud from the plasma membrane of
infected cells, suggesting that phosphatidylserine is likely flipped to the outer
leaflet of the plasma membrane in infected cells for EBOV virions to acquire it.
Currently, the intracellular dynamics of phosphatidylserine during EBOV infection
are poorly understood. Here, we explored the role of XK-related protein (Xkr) 8,
which is a scramblase responsible for exposure of phosphatidylserine in the
plasma membrane of apoptotic cells, to understand its significance in
phosphatidylserine-dependent entry of EBOV. We found that Xkr8 and transiently
expressed EBOV glycoprotein GP often co-localized in intracellular vesicles and
the plasma membrane. We also found that co-expression of GP and viral major
matrix protein VP40 promoted incorporation of Xkr8 into ebolavirus-like particles
(VLPs) and exposure of phosphatidylserine on their surface, although only a
limited amount of phosphatidylserine was exposed on the surface of the cells
expressing GP and/or VP40. Downregulating Xkr8 or blocking caspase-mediated Xkr8
activation did not affect VLP production, but they reduced the amount of
phosphatidylserine on the VLPs and their uptake in recipient cells. Taken
together, our findings indicate that Xkr8 is trafficked to budding sites via GP
containing vesicles, is incorporated into VLPs, and then promote the entry of the
released EBOV to cells in a phosphatidylserine-dependent manner.
PMID- 29338050
TI - Correction: Utilization of urea and expression profiles of related genes in the
dinoflagellate Prorocentrum donghaiense.
AB - [This corrects the article DOI: 10.1371/journal.pone.0187837.].
PMID- 29338049
TI - Contribution of the ankle-brachial index to improve the prediction of coronary
risk: The ARTPER cohort.
AB - BACKGROUND: The different cardiovascular risk prediction scales currently
available are not sufficiently sensitive. AIM: The aim of the present study was
to analyze the contribution of the ankle-brachial index (ABI) added to the
Framingham and REGICOR risk scales for the reclassification of cardiovascular
risk after a 9-year follow up of a Mediterranean population with low
cardiovascular risk. DESIGN AND SETTING: A population-based prospective cohort
study was performed in the province of Barcelona, Spain. METHOD: A total of 3,786
subjects >49 years were recruited from 2006-2008. Baseline ABI was performed and
cardiovascular risk was calculated with the Framingham and REGICOR scales. The
participants were followed until November 2016 by telephone and review of the
clinical history every 6 months to confirm the possible appearance of
cardiovascular events. RESULTS: 2,716 individuals participated in the study.
There were 126 incidental cases of first coronary events (5%) during follow up.
The incidence of coronary events in patients with ABI <0.9 was 4-fold greater
than that of subjects with a normal ABI (17.2/1,000 persons-year versus 4.8/1,000
persons-year). Improvement in the predictive capacity of REGICOR scale was
observed on including ABI in the model, obtaining a net reclassification
improvement of 7% (95% confidence interval 0%-13%) for REGICOR+ ABI. Framingham +
ABI obtained a NRI of 4% (-2%-11%). CONCLUSION: The results of the present study
support the addition of the ABI as a tool to help in the reclassification of
cardiovascular risk and to confirm the greater incidence of coronary events in
patients with ABI < 0.9.
PMID- 29338051
TI - Correction: Cordycepin promotes apoptosis in renal carcinoma cells by activating
the MKK7-JNK signaling pathway through inhibition of c-FLIPL expression.
AB - [This corrects the article DOI: 10.1371/journal.pone.0186489.].
PMID- 29338052
TI - Correction: Diversification dynamics, species sorting, and changes in the
functional diversity of marine benthic gastropods during the Pliocene-Quaternary
at temperate western South America.
AB - [This corrects the article DOI: 10.1371/journal.pone.0187140.].
PMID- 29338053
TI - Selenium regulation of selenoprotein enzyme activity and transcripts in a pilot
study with Founder strains from the Collaborative Cross.
AB - Rodents and humans have 24-25 selenoproteins, and these proteins contain the 21st
amino acid, selenocysteine, incorporated co-translationally into the peptide
backbone in a series of reactions dependent on at least 6 unique gene products.
In selenium (Se) deficiency, there is differential regulation of selenoprotein
expression, whereby levels of some selenoproteins and their transcripts decrease
dramatically in Se deficiency, but other selenoprotein transcripts are spared
this decrease; the underlying mechanism, however, is not fully understood. To
begin explore the genetic basis for this variation in regulation by Se status in
a pilot study, we fed Se-deficient or Se-adequate diets (0.005 or 0.2 MUg Se/g,
respectively) for eight weeks to the eight Founder strains of the Collaborative
Cross. We found rather uniform expression of selenoenzyme activity for
glutathione peroxidase (Gpx) 3 in plasma, Gpx1 in red blood cells, and Gpx1,
Gpx4, and thioredoxin reductase in liver. In Founder mice, Se deficiency
decreased each of these activities to a similar extent. Regulation of
selenoprotein transcript expression by Se status was also globally retained
intact, with dramatic down-regulation of Gpx1, Selenow, and Selenoh transcripts
in all 8 strains of Founder mice. These results indicate that differential
regulation of selenoprotein expression by Se status is an essential aspect of Se
metabolism and selenoprotein function. A few lone differences in Se regulation
were observed for individual selenoproteins in this pilot study, but these
differences did not single-out one strain or one selenoprotein that consistently
had unique Se regulation of selenoprotein expression. These differences should be
affirmed in larger studies; use of the Diversity Outbred and Collaborative Cross
strains may help to better define the functions of these selenoproteins.
PMID- 29338054
TI - Correction: Selective serotonin reuptake inhibitors and venlafaxine in pregnancy:
Changes in drug disposition.
AB - [This corrects the article DOI: 10.1371/journal.pone.0181082.].
PMID- 29338056
TI - Context-dependent autoprocessing of human immunodeficiency virus type 1 protease
precursors.
AB - HIV-1 protease autoprocessing is responsible for liberation of free mature
protease (PR) from the Gag-Pol polyprotein precursor. A cell-based model system
was previously developed to examine the autoprocessing mechanism of fusion
precursors carrying the p6*-PR miniprecursor sandwiched between various proteins
or epitopes. We here report that precursor autoprocessing is context-dependent as
its activity and outcomes can be modulated by sequences upstream of p6*-PR. This
was exemplified by the 26aa maltose binding protein (MBP) signal peptide (SigP)
when placed at the N-terminus of a fusion precursor. The mature PRs released from
SigP-carrying precursors are resistant to self-degradation whereas those released
from SigP-lacking fusion precursors are prone to self-degradation. A H69D
mutation in PR abolished autoprocessing of SigP-containing fusion precursors
whereas it only partially suppressed autoprocessing of fusion precursors lacking
SigP. An autoprocessing deficient GFP fusion precursor with SigP exhibited a
subcellular distribution pattern distinct from the one without it in transfected
HeLa cells. Furthermore, a SigP fusion precursor carrying a substitution at the
P1 position released the mature PR and PR-containing fragments that were
different from those released from the precursor carrying the same mutation but
lacking SigP. We also examined autoprocessing outcomes in viral particles
produced by a NL4-3 derived proviral construct and demonstrated the existence of
several PR-containing fragments along with the mature PR. Some of these resembled
the SigP precursor autoprocessing outcomes. This finding of context-dependent
modulation reveals the complexity of precursor autoprocessing regulation that
most likely accompanies sequence variation imposed by the evolution of the
upstream Gag moiety.
PMID- 29338055
TI - A novel Gerstmann-Straussler-Scheinker disease mutation defines a precursor for
amyloidogenic 8 kDa PrP fragments and reveals N-terminal structural changes
shared by other GSS alleles.
AB - To explore pathogenesis in a young Gerstmann-Straussler-Scheinker Disease (GSS)
patient, the corresponding mutation, an eight-residue duplication in the
hydrophobic region (HR), was inserted into the wild type mouse PrP gene.
Transgenic (Tg) mouse lines expressing this mutation (Tg.HRdup) developed
spontaneous neurologic syndromes and brain extracts hastened disease in low
expressor Tg.HRdup mice, suggesting de novo formation of prions. While Tg.HRdup
mice exhibited spongiform change, PrP aggregates and the anticipated GSS hallmark
of a proteinase K (PK)-resistant 8 kDa fragment deriving from the center of PrP,
the LGGLGGYV insertion also imparted alterations in PrP's unstructured N
terminus, resulting in a 16 kDa species following thermolysin exposure. This
species comprises a plausible precursor to the 8 kDa PK-resistant fragment and
its detection in adolescent Tg.HRdup mice suggests that an early start to
accumulation could account for early disease of the index case. A 16 kDa
thermolysin-resistant signature was also found in GSS patients with P102L, A117V,
H187R and F198S alleles and has coordinates similar to GSS stop codon mutations.
Our data suggest a novel shared pathway of GSS pathogenesis that is fundamentally
distinct from that producing structural alterations in the C-terminus of PrP, as
observed in other prion diseases such as Creutzfeldt-Jakob Disease and scrapie.
PMID- 29338057
TI - RNA-sequencing analysis of fungi-induced transcripts from the bamboo wireworm
Melanotus cribricollis (Coleoptera: Elateridae) larvae.
AB - Larvae of Melanotus cribricollis, feed on bamboo shoots and roots, causing
serious damage to bamboo in Southern China. However, there is currently no
effective control measure to limit the population of this underground pest.
Previously, a new entomopathogenic fungal strain isolated from M. cribricollis
larvae cadavers named Metarhizium pingshaense WP08 showed high pathogenic
efficacy indoors, indicated that the fungus could be used as a bio-control
measure. So far, the genetic backgrounds of both M. cribricollis and M.
pingshaense WP08 were blank. Here, we analyzed the whole transcriptome of M.
cribricollis larvae, infected with M. pingshaense WP08 or not, using high
throughput next generation sequencing technology. In addition, the transcriptome
sequencing of M. pingshaense WP08 was also performed for data separation of those
two non-model species. The reliability of the RNA-Seq data was also validated
through qRT-PCR experiment. The de novo assembly, functional annotation, sequence
comparison of four insect species, and analysis of DEGs, enriched pathways, GO
terms and immune related candidate genes were operated. The results indicated
that, multiple defense mechanisms of M. cribricollis larvae are initiated to
protect against the more serious negative effects caused by fungal infection. To
our knowledge, this was the first report of transcriptome analysis of Melanotus
spp. infected with a fungus, and it could provide insights to further explore
insect-fungi interaction mechanisms.
PMID- 29338058
TI - Menstrual and reproductive factors and risk of breast cancer: A case-control
study in the Fez region, Morocco.
AB - BACKGROUND: Breast cancer is the most common cancer in women worldwide. In the
Moroccan context, the role of well-known reproductive factors in breast cancer
remains poorly documented. The aim of this study was to explore the relationship
between menstrual and reproductive factors and breast cancer risk in Moroccan
women in the Fez region. METHODS: A case-control study was conducted at the
Hassan II University Hospital of Fez between January 2014 and April 2015. A total
of 237 cases of breast cancer and 237 age-matched controls were included.
Information on sociodemographic characteristics, menstrual and reproductive
history, family history of breast cancer, and lifestyle factors was obtained
through a structured questionnaire. Conditional logistic regression models were
used to estimate odds ratios and 95% confidence intervals for breast cancer by
menstrual and reproductive factors adjusted for potential confounders. RESULTS:
Early menarche (OR = 1.60, 95% CI: 1.08-2.38) and nulliparity (OR = 3.77, 95% CI:
1.98-7.30) were significantly related to an increased risk of breast cancer,
whereas an early age at first full-term pregnancy was associated with a decreased
risk of breast cancer (OR = 0.41, 95% CI: 0.25-0.65). CONCLUSION: The results of
this study confirm the role of established reproductive factors for breast cancer
in Moroccan women. It identified some susceptible groups at high risk of breast
cancer. Preventive interventions and screening should focus on these groups as a
priority. These results should be confirmed in a larger, multicenter study.
PMID- 29338059
TI - Hemodynamic characteristics of hyperplastic remodeling lesions in cerebral
aneurysms.
AB - BACKGROUND & PURPOSE: Hyperplastic remodeling (HR) lesions are sometimes found on
cerebral aneurysm walls. Atherosclerosis is the results of HR, which may cause an
adverse effect on surgical treatment for cerebral aneurysms. Previous studies
have demonstrated that atherosclerotic changes had a correlation with certain
hemodynamic characteristics. Therefore, we investigated local hemodynamic
characteristics of HR lesions of cerebral aneurysms using computational fluid
dynamics (CFD). METHODS: Twenty-four cerebral aneurysms were investigated using
CFD and intraoperative video recordings. HR lesions and red walls were confirmed
on the intraoperative images, and the qualification points were determined on the
center of the HR lesions and the red walls. The qualification points were set on
the virtual operative images for evaluation of wall shear stress (WSS),
normalized WSS (NWSS), oscillatory shear index (OSI), relative residence time
(RRT), and aneurysm formation indicator (AFI). These hemodynamic parameters at
the qualification points were compared between HR lesions and red walls. RESULTS:
HR lesions had lower NWSS, lower AFI, higher OSI and prolonged RRT compared with
red walls. From analysis of the receiver-operating characteristic curve for
hemodynamic parameters, OSI was the most optimal hemodynamic parameter to predict
HR lesions (area under the curve, 0.745; 95% confidence interval, 0.603-0.887;
cutoff value, 0.00917; sensitivity, 0.643; specificity, 0.893; P<0.01). With
multivariate logistic regression analyses using stepwise method, NWSS was
significantly associated with the HR lesions. CONCLUSIONS: Although low NWSS was
independently associated with HR lesions, OSI is the most valuable hemodynamic
parameter to distinguish HR lesions from red walls.
PMID- 29338060
TI - Biofeedback effect of hybrid assistive limb in stroke rehabilitation: A proof of
concept study using functional near infrared spectroscopy.
AB - INTRODUCTION: Robot-assisted rehabilitation has been increasingly drawing
attention in the field of neurorehabilitation. The hybrid assistive limb (HAL) is
an exoskeleton robot developed based on the "interactive biofeedback" theory, and
several studies have shown its efficacy for patients with stroke. We aimed to
investigate the mechanisms of the facilitative effect of neurorehabilitation
using a single-joint HAL (HAL-SJ) and functional near-infrared spectroscopy
(fNIRS). MATERIALS AND METHODS: Subacute stroke patients admitted to our hospital
were assessed in this study for HAL eligibility. We evaluated motor-related
cortical activity using an fNIRS system at baseline and immediately after HAL-SJ
treatment on the same day. Cortical activity was determined through the relative
changes in the hemoglobin concentrations. For statistical analysis, we compared
the number of flexion/extension movements before and immediately after HAL-SJ
treatment using paired t-test. fNIRS used both the methods of statistical
parametric mapping and random effect analysis. RESULTS: We finally included 10
patients (eight men, two women; mean age: 66.8 +/- 12.0 years). The mean number
of flexion/extension movements within 15 s increased significantly from 4.2 +/-
3.1 to 5.3 +/- 4.1 immediately after training. fNIRS showed increased cortical
activation in the primary motor cortex of the ipsilesional hemisphere immediately
after HAL-SJ treatment compared to the baseline condition. CONCLUSIONS: This
study is the first to support the concept of the biofeedback effect from the
perspective of changes in cortical activity measured with an fNIRS system. The
biofeedback effect of HAL immediately increased the task-related cortical
activity, and this may address the functional recovery. Further studies are
warranted to support our findings.
PMID- 29338061
TI - Feasibility of cell-based therapy combined with descemetorhexis for treating
Fuchs endothelial corneal dystrophy in rabbit model.
AB - Corneal transparency is maintained by the corneal endothelium through its pump
and barrier function. Severe corneal endothelial damage results in dysregulation
of water flow and eventually causes corneal haziness and deterioration of visual
function. In 2013, we initiated clinical research of cell-based therapy for
treating corneal decompensation. In that study, we removed an 8-mm diameter
section of damaged corneal endothelium without removing Descemet's membrane (the
basement membrane of the corneal endothelium) and then injected cultured human
corneal endothelial cells (CECs) into the anterior chamber. However, Descemet's
membrane exhibits clinically abnormal structural features [i.e., multiple
collagenous excrescences (guttae) and thickening] in patients with Fuchs
endothelial corneal dystrophy (FECD) and the advanced cornea guttae adversely
affects the quality of vision, even in patients without corneal edema. The
turnover time of cornea guttae is also not certain. Therefore, we used a rabbit
model to evaluate the feasibility of Descemet's membrane removal in the optical
zone only, by performing a small 4-mm diameter descemetorhexis prior to CEC
injection. We showed that the corneal endothelium is regenerated both on the
corneal stroma (the area of Descemet's membrane removal) and on the intact
peripheral Descemet's membrane, based on the expression of function-related
markers and the restoration of corneal transparency. Recovery of the corneal
transparency and central corneal thickness was delayed in areas of Descemet's
membrane removal, but the cell density of the regenerated corneal endothelium and
the thickness of the central corneal did not differ between the areas with and
without residual Descemet's membrane at 14 days after CEC injection. Here, we
demonstrate that removal of a pathological Descemet's membrane by a small
descemetorhexis is a feasible procedure for use in combination with cell-based
therapy. The current strategy might be beneficial for improving visual quality
after CEC injection as a treatment for FECD.
PMID- 29338062
TI - An imaged-based inverse finite element method to determine in-vivo mechanical
properties of the human trabecular meshwork.
AB - Aim: Previous studies have shown that the trabecular meshwork (TM) is
mechanically stiffer in glaucomatous eyes as compared to normal eyes. It is
believed that elevated TM stiffness increases resistance to the aqueous humor
outflow, producing increased intraocular pressure (IOP). It would be advantageous
to measure TM mechanical properties in vivo, as these properties are believed to
play an important role in the pathophysiology of glaucoma and could be useful for
identifying potential risk factors. The purpose of this study was to develop a
method to estimate in-vivo TM mechanical properties using clinically available
exams and computer simulations. Design: Inverse finite element simulation.
Methods: A finite element model of the TM was constructed from optical coherence
tomography (OCT) images of a healthy volunteer before and during IOP elevation.
An axisymmetric model of the TM was then constructed. Images of the TM at a
baseline IOP level of 11, and elevated level of 23 mmHg were treated as the
undeformed and deformed configurations, respectively. An inverse modeling
technique was subsequently used to estimate the TM shear modulus (G). An
optimization technique was used to find the shear modulus that minimized the
difference between Schlemm's canal area in the in-vivo images and simulations.
Results: Upon completion of inverse finite element modeling, the simulated area
of the Schlemm's canal changed from 8,889 um2 to 2,088 um2, similar to the
experimentally measured areal change of the canal (from 8,889 um2 to 2,100 um2).
The calculated value of shear modulus was found to be 1.93 kPa, (implying an
approximate Young's modulus of 5.75 kPa), which is consistent with previous ex
vivo measurements. Conclusion: The combined imaging and computational simulation
technique provides a unique approach to calculate the mechanical properties of
the TM in vivo without any surgical intervention. Quantification of such
mechanical properties will help us examine the mechanistic role of TM
biomechanics in the regulation of IOP in healthy and glaucomatous eyes.
PMID- 29338063
TI - Formalizing Knowledge in Multi-Scale Agent-Based Simulations.
AB - Multi-scale, agent-based simulations of cellular and tissue biology are
increasingly common. These simulations combine and integrate a range of
components from different domains. Simulations continuously create, destroy and
reorganize constituent elements causing their interactions to dynamically change.
For example, the multi-cellular tissue development process coordinates molecular,
cellular and tissue scale objects with biochemical, biomechanical, spatial and
behavioral processes to form a dynamic network. Different domain specific
languages can describe these components in isolation, but cannot describe their
interactions. No current programming language is designed to represent in human
readable and reusable form the domain specific knowledge contained in these
components and interactions. We present a new hybrid programming language
paradigm that naturally expresses the complex multi-scale objects and dynamic
interactions in a unified way and allows domain knowledge to be captured,
searched, formalized, extracted and reused.
PMID- 29338065
TI - Corrigendum to "Tooth Reattachment and Palatal Veneer on a Multidisciplinary
Approach of Crown Fractures in Upper Central Incisors".
AB - [This corrects the article DOI: 10.1155/2017/4702635.].
PMID- 29338064
TI - Reflections on 15 Years in the Global Tobacco Trenches.
AB - This paper is based on my 2017 Research Laureate Presentation at the Annual
Scientific Meeting of the American Academy of Health Behavior in Tucson, Arizona.
It provides a brief overview of the history of the smoking epidemic, and
describes my work in global tobacco control, focusing on my experiences over the
last 15 years as a co-founder and intervention director of the Syrian Center for
Tobacco Studies (SCTS) in Aleppo, Syria. The SCTS is an NIH-funded research
center that draws on a broad range of complementary expertise and resources from
developed and developing nations to address the tobacco epidemic in the Arab
World. The SCTS strives to serve as a model of scientific excellence and
commitment to the health of people in the Middle East and beyond. Major research
streams using qualitative, epidemiological, clinical lab, and intervention
methodologies are reviewed, along with some of the successes and challenges
encountered since the SCTS's founding.
PMID- 29338066
TI - Endoscopic scoring indices for evaluation of disease activity in ulcerative
colitis.
AB - BACKGROUND: Endoscopic assessment of mucosal disease activity is routinely used
to determine eligibility and response to therapy in clinical trials of ulcerative
colitis. The operating properties of the existing endoscopic scoring indices are
unclear. OBJECTIVES: A systematic review was undertaken to evaluate the
development and operating characteristics of endoscopic scoring indices for the
evaluation of ulcerative colitis. SEARCH METHODS: We searched MEDLINE, Embase and
CENTRAL from inception to 5 July 2016. We also searched references and conference
proceedings (Digestive Disease Week, United European Gastroenterology Week,
European Crohn's and Colitis Organization). SELECTION CRITERIA: Any study design
(e.g. randomized controlled trials, cohort studies, case series) that evaluated
endoscopic indices for evaluation of ulcerative colitis disease activity were
considered for inclusion. Eligible participants were adult patients (> 16 years),
diagnosed with ulcerative colitis using conventional clinical, radiologic and
endoscopic criteria. DATA COLLECTION AND ANALYSIS: Two authors independently
reviewed the studies identified from the literature search. These authors also
independently extracted and recorded data on the number of patients enrolled;
number of patients per treatment arm; patient characteristics including age and
gender distribution; endoscopic index; and outcomes such as reliability (intra
rater and inter-rater), validity (content, construct, criterion), responsiveness
and feasibility. Any disagreements regarding study inclusion or data extraction
were resolved by discussion and consensus with a third author. Risk of bias was
assessed by determining whether assessors were blinded to clinical information
and whether assessors scored the endoscopic index independently. We also assessed
the methodological quality of the validation studies using the COSMIN checklist
MAIN RESULTS: A total of 23 reports of 20 studies met the pre-defined inclusion
criteria and were included in the review. Of the 20 included validation studies,
19 endoscopic scoring indices were assessed, including the Azzolini
Classification, Baron Score, Blackstone Endoscopic Interpretation, Chinese
Grading System of Ulcerative Colitis, Endoscopic Activty Index, Jeroen Score,
Magnifying Colonoscopy Grade, Matts Score, Mayo Clinic Endoscopic Subscore,
Modified Baron Score, Modified Mayo Clinic Endoscopic Subscore, Osada Score,
Rachmilewtiz Endoscopic Score, St. Mark's Index, Ulcerative Colitis Colonoscopic
Index of Serverity (UCCIS), endoscopic component of the Ulcerative Colitis
Disease Activity Index (UCDAI), Ulcerative Colitis Endoscopic Index of Severity
(UCEIS), Witts Sigmoidoscopic Score and Watson Grade. The individuals who
performed the endoscopic scoring were blinded to clinical and/or histologic
information in ten of the included studies, not blinded to clinical and/or
histologic information in one of the included studies, and it was unclear whether
blinding occurred in the remaining nine included studies. Independent observation
was confirmed in four of the included studies, unclear in five of the included
studies, and non-applicable (since inter-rater reliability was not assessed) in
the remaining eleven included studies. The methodological quality (COSMIN
checklist) of most of the included studies was rated as 'good' or 'excellent'.
One study that assessed responsiveness was rated as 'fair'. The inter-rater
reliability of nine endoscopic scoring indices including the Baron Score,
Blackstone Endoscopic Interpretation, Endoscopic Activity Index, Matts Score,
Mayo Clinic Endoscopic Subscore, Osada Score, UCCIS, UCEIS, Watson Grade was
assessed in seven studies, with estimates of correlation, k, ranging from 0.44 to
0.97. The iIntra-rater reliability of seven endoscopic scoring indices including
the Baron Score, Blackstone Endoscopic Interpretation, Matts Score, Mayo Clinic
Endoscopic Subscore, Osada Score, UCCIS and UCEIS was assessed in three studies,
with estimates of correlation, k, ranging from 0.41 to 0.86. No studies assessed
content validity. Three studies evaluated the criterion validity of three
endoscopic scoring indices including the Rachmilewitz Endoscopic Score,
Magnifying Colonoscopy Grade and the UCCIS. These indices were correlated with
objective markers of disease activity including albumin, blood leukocytes, C
reactive protein, fecal calprotectin, hemoglobin, mucosal interleukin-8
concentration and platelet count. Correlation estimates ranged from r = -0.19 to
0.83. Thirteen endoscopic scoring indices were tested for construct validity in
13 studies. Estimates of correlation between the endoscopic scoring indices and
other measures of disease activity ranged from r = 0.27 to 0.93. Two studies
explored the responsiveness of four endoscopic scoring indices including the Mayo
Endoscopic Subscore, Modified Baron Score, Modified Mayo Endoscopic Subscore and
UCEIS. One study concluded that the Modified Baron Score, Modified Mayo
Endoscopic Subscore and UCEIS had similar responsiveness for detecting disease
change in ulcerative colitis. The other included study concluded that the UCEIS
may be the most accurate endoscopic scoring tool. None of the included studies
formally assessed feasibility. AUTHORS' CONCLUSIONS: While the UCEIS, UCCIS and
Mayo Clinic Endoscopic Subscore have undergone extensive validation, none of
these instruments have been fully validated and only two studies assessed
responsiveness. Further research on the operating properties of these indices is
needed given the lack of a fully-validated endoscopic scoring instrument for the
evaluation of disease activity in ulcerative colitis.
PMID- 29338067
TI - The influence of delayed cord clamping and cord milking on inflammatory cytokines
in umbilical vein and neonatal circulation.
AB - INTRODUCTION: The purpose of the present study was to compare the levels of tumor
necrosis factor alpha (TNF-alpha), and interleukins (IL) 1, 6, 8 and 10 in the
umbilical cord and neonatal circulation among neonates with early and late cord
clamping. MATERIAL AND METHODS: A consecutive series of 76 cases of uncomplicated
pregnancy and an uneventful parturition was evaluated. In 40 cases, delayed cord
clamping was used and in the remaining 36, early cord clamping was practiced.
Blood samples were collected from the umbilical vein immediately after cord
clamping and at 24 h from the median cubital or basilic vein of the neonate.
RESULTS: Significant differences were noted in the hematocrit and hemoglobin
levels at 24 h that favored delayed clamping. None of the evaluated markers of
inflammation differ between the two groups. Spearman's rho revealed a significant
correlation between umbilical cord TNF-alpha and TNF-alpha neonatal values at 24
h (r = 0.551, p = 0.022) in the early clamped group. Significant correlations
were also noted between umbilical cord TNF-alpha and TNF-alpha neonatal values at
24 h (r = 0.728, p = 0.001), umbilical cord IL-10 and neonatal IL-10 at 24 h (r =
0.487, p = 0.047) and umbilical cord IL-1b and neonatal IL-1b at 24 h (r = 0.516,
p = 0.034). CONCLUSIONS: Delayed cord clamping or cord milking does not alter the
levels of inflammatory cytokines in cord blood and neonatal serum. Future studies
should evaluate the impact of delayed cord clamping in selected high-risk
pregnancies.
PMID- 29338068
TI - Single and combined effects of plant-derived and synthetic cannabinoids on
cognition and cannabinoid-associated withdrawal signs in mice.
AB - BACKGROUND AND PURPOSE: It has been suggested that the non-euphorogenic
phytocannabinoid cannabidiol (CBD) can ameliorate adverse effects of Delta9
tetrahydrocannabinol (THC). We determined whether CBD ameliorates cognitive
deficits and withdrawal signs induced by cannabinoid CB1 /CB2 receptor agonists
or produces these pharmacological effects on its own. EXPERIMENTAL APPROACH: The
effects of THC or the CB1 /CB2 receptor full agonist WIN55212 alone, CBD alone or
their combination were tested across a range of doses. Cognitive effects were
assessed in C57BL/6 mice in a conditional discrimination task and in the Barnes
maze. Cannabinoid withdrawal signs were assessed following precipitated
withdrawal by acute administration of the CB1 receptor antagonist SR141716, the 5
HT1A receptor antagonist WAY100635, the TRPV1 receptor antagonist capsazepine or
the adenosine A2A receptor antagonist SCH58261. KEY RESULTS: THC produced
significant motor and cognitive impairment in the Barnes maze task, none of which
were attenuated by the addition of CBD. CBD alone did not affect cognitive
performance. Precipitation of withdrawal signs by SR141716 occurred in mice
chronically treated with THC or WIN55,212. These withdrawal signs were not
attenuated by addition of chronic CBD. Chronic treatment with CBD alone did not
induce withdrawal signs precipitated by SR141716 or WAY100635. Chronic CBD
treatment also produced anxiolysis, which was not altered by attempting to
precipitate withdrawal-induced anxiety with a range of antagonists. CONCLUSIONS
AND IMPLICATIONS: CBD as a monotherapy may prove to be a safer pharmacological
agent, than CB1 receptor agonists alone or in combination with CBD, for the
treatment of several disorders.
PMID- 29338069
TI - Cesarean scar niche and uterotomy closure technique.
PMID- 29338071
TI - The financial burden and distress of patients with cancer: Understanding and
stepping-up action on the financial toxicity of cancer treatment.
AB - "Financial toxicity" has now become a familiar term used in the discussion of
cancer drugs, and it is gaining traction in the literature given the high price
of newer classes of therapies. However, as a phenomenon in the contemporary
treatment and care of people with cancer, financial toxicity is not fully
understood, with the discussion on mitigation mainly geared toward interventions
at the health system level. Although important, health policy prescriptions take
time before their intended results manifest, if they are implemented at all. They
require corresponding strategies at the individual patient level. In this review,
the authors discuss the nature of financial toxicity, defined as the objective
financial burden and subjective financial distress of patients with cancer, as a
result of treatments using innovative drugs and concomitant health services. They
discuss coping with financial toxicity by patients and how maladaptive coping
leads to poor health and nonhealth outcomes. They cover management strategies for
oncologists, including having the difficult and urgent conversation about the
cost and value of cancer treatment, availability of and access to resources, and
assessment of financial toxicity as part of supportive care in the provision of
comprehensive cancer care. CA Cancer J Clin 2018;68:153-165. (c) 2018 American
Cancer Society.
PMID- 29338070
TI - The use of chemogenetics in behavioural neuroscience: receptor variants,
targeting approaches and caveats.
AB - The last decade has seen major advances in neuroscience tools allowing us to
selectively modulate cellular pathways in freely moving animals. Chemogenetic
approaches such as designer receptors exclusively activated by designer drugs
(DREADDs) permit the remote control of neuronal function by systemic drug
administration. These approaches have dramatically advanced our understanding of
the neural control of behaviour. Here, we review the different techniques and
genetic approaches available for the restriction of chemogenetic receptors to
defined neuronal populations. We highlight the use of a dual virus approach to
target specific circuitries and the effectiveness of different routes of
administration of designer drugs. Finally, we discuss the potential caveats
associated with DREADDs including off-target effects of designer drugs, the
effects of chronic chemogenetic receptor activation and the issue of collateral
projections associated with DREADD activation and inhibition.
PMID- 29338072
TI - Targeting HER2 in colorectal cancer: The landscape of amplification and short
variant mutations in ERBB2 and ERBB3.
AB - BACKGROUND: In contrast to lung cancer, few precision treatments are available
for colorectal cancer (CRC). One rapidly emerging treatment target in CRC is
ERBB2 (human epidermal growth factor receptor 2 [HER2]). Oncogenic alterations in
HER2, or its dimerization partner HER3, can underlie sensitivity to HER2-targeted
therapies. METHODS: In this study, 8887 CRC cases were evaluated by comprehensive
genomic profiling for genomic alterations in 315 cancer-related genes, tumor
mutational burden, and microsatellite instability. This cohort included both
colonic (7599 cases; 85.5%) and rectal (1288 cases; 14.5%) adenocarcinomas.
RESULTS: A total of 569 mCRCs were positive for ERBB2 (429 cases; 4.8%) and/or
ERBB3 (148 cases; 1.7%) and featured ERBB amplification, short variant
alterations, or a combination of the 2. High tumor mutational burden (>=20
mutations/Mb) was significantly more common in ERBB-mutated samples, and ERBB3
mutated CRCs were significantly more likely to have high microsatellite
instability (P<.002). Alterations affecting KRAS (27.3%) were significantly
underrepresented in ERBB2-amplified samples compared with wild-type CRC samples
(51.8%), and ERBB2- or ERBB3-mutated samples (49.0% and 60.8%, respectively)
(P<.01). Other significant differences in mutation frequency were observed for
genes in the PI3K/MTOR and mismatch repair pathways. CONCLUSIONS: Although
observed less often than in breast or upper gastrointestinal carcinomas,
indications for which anti-HER2 therapies are approved, the percentage of CRC
with ERBB genomic alterations is significant. Importantly, 32% of ERBB2-positive
CRCs harbor short variant alterations that are undetectable by routine
immunohistochemistry or fluorescence in situ hybridization testing. The success
of anti-HER2 therapies in ongoing clinical trials is a promising development for
patients with CRC. Cancer 2018;124:1358-73. (c) 2018 Foundation Medicine, Inc.
Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
PMID- 29338073
TI - Impact of time to testosterone rebound and comorbidity on the risk of cause
specific mortality in men with unfavorable-risk prostate cancer.
AB - BACKGROUND: Herein, the authors evaluated how the time to testosterone rebound
(TTR) after radiotherapy (RT) and 6 months of androgen deprivation therapy (ADT)
impacted the risk of prostate cancer-specific mortality (PCSM) and cardiovascular
specific mortality (CVM) among men with varying comorbidity extent. METHODS:
Between 1995 and 2001, a total of 206 men who were randomized to receive RT
either alone or with 6 months of ADT for unfavorable-risk PC and who had a
comorbidity score assigned using the Adult Comorbidity Evaluation 27 metric
comprised the study cohort. Multivariable competing risk regression was used to
evaluate the impact of and possible interaction between comorbidity and TTR on
PCSM and CVM. RESULTS: After a median follow-up of 18.19 years, 30 men (18.6%),
39 men (24.2%), and 92 men (57.1%), respectively, had died of PC, CV disease, or
other causes. As TTR increased, PCSM significantly decreased in men with no or
minimal (adjusted hazard ratio [AHR], 0.53, 95% confidence interval [95% CI],
0.34-0.84 [P =.007]) and moderate to severe (AHR, 0.37; 95% CI, 0.14-0.99 [P =
.048]) comorbidity. However, increasing TTR significantly increased the risk of
CVM among men with moderate to severe comorbidity (AHR, 1.87; 95% CI, 1.40-2.49
[P <.001]), but not those with no or minimal comorbidity (AHR, 0.86; 95% CI, 0.57
1.29 [P =.46]), leading to a significant interaction between TTR and comorbidity
(P = .001). CONCLUSIONS: The results of the current study indicate that
considering an intermittent course of ADT such that the TTR approaches 18 months,
instead of continuous long-term administration of ADT, in men with moderate to
severe comorbidity and high-risk PC may reduce the increased risk of CVM without
increasing the risk of PCSM. Cancer 2018;124:1391-9. (c) 2018 American Cancer
Society.
PMID- 29338075
TI - Liver kinase B1/AMP-activated protein kinase-mediated regulation by
gentiopicroside ameliorates P2X7 receptor-dependent alcoholic hepatosteatosis.
AB - BACKGROUND AND PURPOSE: Regulating P2X7 receptor-mediated activation of NLRP3
inflammasomes could be a therapeutic strategy to treat alcoholic hepatosteatosis.
We investigated whether this process was modulated by gentiopicroside, the main
active secoiridoid glycoside from Gentiana manshurica Kitagawa. EXPERIMENTAL
APPROACH: In vivo models of acute and chronic alcoholic hepatosteatosis were
established by intragastrically administered ethanol or using chronic plus binge
ethanol feeding of Lieber-DeCarli liquid diet to male C57BL/6 mice. In vitro,
HepG2 cells were treated with ethanol. RAW 264.7 macrophages and murine bone
marrow-derived macrophages (BMDMs) were stimulated with LPS and ATP. KEY RESULTS:
In both the acute and chronic alcohol-induced mouse hepatosteatosis models,
gentiopicroside decreased serum aminotransferases and triglyceride accumulation.
Up-regulated SREBP1, down-regulated PPARalpha and phosphorylated acetyl-CoA
carboxylase caused by acute and chronic alcohol feeding were modulated by
gentiopicroside, through the elevation of LKB1 and AMPK. Suppression of P2X7
receptor-NLRP3 activation by gentiopicroside inhibited IL-1beta production. In
ethanol-exposed HepG2 cells, gentiopicroside reduced lipogenesis and promoted
lipid oxidation via activation of P2X7 receptor-NLRP3 inflammasomes. Genetic or
pharmacological blockade of P2X7 receptors enhanced AMPK activity and reduced
SREBP1 expression in ethanol-treated HepG2 cells. Gentiopicroside down-regulated
P2X7 receptor-mediated inflammatory responses in LPS/ATP-stimulated RAW 264.7
macrophages and BMDMs. IL-1beta from macrophages accelerated lipid accumulation
in hepatocytes. Depleting macrophages by clodronate liposomes ameliorated
alcoholic hepatosteatosis, and it was further alleviated by gentiopicroside.
CONCLUSIONS AND IMPLICATIONS: Activation of LKB1/AMPK signalling by
gentiopicroside was mediated by the P2X7 receptor-NLRP3 inflammasome, suggesting
the therapeutic value of blocking P2X7 receptors in the treatment of alcoholic
hepatosteatosis.
PMID- 29338074
TI - Adaptive immune education by gut microbiota antigens.
AB - Host-microbiota mutualism has been established during long-term co-evolution. A
diverse and rich gut microbiota plays an essential role in the development and
maturation of the host immune system. Education of the adaptive immune
compartment by gut microbiota antigens is important in establishing immune
balance. In particular, a critical time frame immediately after birth provides a
'window of opportunity' for the development of lymphoid structures,
differentiation and maturation of T and B cells and, most importantly,
establishment of immune tolerance to gut commensals. Depending on the
colonization niche, antigen type and metabolic property of different gut
microbes, CD4 T-cell responses vary greatly, which results in differentiation
into distinct subsets. As a consequence, certain bacteria elicit effector-like
immune responses by promoting the production of pro-inflammatory cytokines such
as interferon-gamma and interleukin-17A, whereas other bacteria favour the
generation of regulatory CD4 T cells and provide help with gut homeostasis. The
microbiota have profound effects on B cells also. Gut microbial exposure leads to
a continuous diversification of B-cell repertoire and the production of T
dependent and -independent antibodies, especially IgA. These combined effects of
the gut microbes provide an elegant educational process to the adaptive immune
network. Contrariwise, failure of this process results in a reduced homeostasis
with the gut microbiota, and an increased susceptibility to various immune
disorders, both inside and outside the gut. With more definitive microbial-immune
relations waiting to be discovered, modulation of the host gut microbiota has a
promising future for disease intervention.
PMID- 29338077
TI - Blenderized Enteral Nutrition Diet Study: Feasibility, Clinical, and Microbiome
Outcomes of Providing Blenderized Feeds Through a Gastric Tube in a Medically
Complex Pediatric Population.
AB - BACKGROUND: Chronically ill children often require feeding via gastrostomy tubes
(G-tubes). Commercial formula is most commonly used for enteral feeding; however,
caregivers have been requesting blenderized tube feeds (BTFs) as an alternative.
The objective of this study was to evaluate the feasibility of using BTFs in a
medically complex pediatric population and assess their impact on clinical
outcomes, as well as the microbiota. METHODS: Twenty pediatric participants were
included. Participants were G-tube dependent and receiving >=75% of their daily
energy requirements from commercial formula. Over 4 weeks, participants were
transitioned from commercial formula to BTF and were monitored for 6 months for
changes in nutrient intake, gastrointestinal symptoms, oral feeding, medication
use, and caregiver perceptions. Changes to intestinal microbiota were monitored
by 16S rDNA-based sequencing. RESULTS: Transition onto BTF was feasible in 17
participants, and 1 participant transitioned to oral feeds. Participants required
50% more calories to maintain their body mass index while on BTFs compared with
commercial formula. BTF micronutrient content was superior to commercial formula.
Prevalence of vomiting and use of acid-suppressive agents significantly decreased
on BTFs. Stool consistency and frequency remained unchanged, while stool softener
use increased. The bacterial diversity and richness in stool samples
significantly increased, while the relative abundance of Proteobacteria
decreased. Caregivers were more satisfied with BTFs and unanimously indicated
they would recommend BTFs. CONCLUSION: Initiation and maintenance of BTFs is not
only feasible in a medically complex pediatric population but can also be
associated with improved clinical outcomes and increased intestinal bacterial
diversity.
PMID- 29338078
TI - Bladder cancer and the National Cancer Data Base: New insight or misinformation?
PMID- 29338076
TI - Hypoxia-inducible transcription factors, HIF1A and HIF2A, increase in aging
mucosal tissues.
AB - Hypoxia (i.e. oxygen deprivation) activates the hypoxia-signalling pathway,
primarily via hypoxia-inducible transcription factors (HIF) for numerous target
genes, which mediate angiogenesis, metabolism and coagulation, among other
processes to try to replenish tissues with blood and oxygen. Hypoxia signalling
dysregulation also commonly occurs during chronic inflammation. We sampled
gingival tissues from rhesus monkeys (Macaca mulatta; 3-25 years old) and total
RNA was isolated for microarray analysis. HIF1A, HIF1B and HIF2A were
significantly different in healthy aged tissues, and both HIF1A and HIF3A were
positively correlated with aging. Beyond these transcription factor alterations,
analysis of patterns of gene expression involved in hypoxic changes in tissues
showed specific increases in metabolic pathway hypoxia-inducible genes, whereas
angiogenesis pathway gene changes were more variable in healthy aging tissues
across the animals. With periodontitis, aging tissues showed decreases in
metabolic gene expression related to carbohydrate/lipid utilization (GBE1, PGAP1,
TPI1), energy metabolism and cell cycle regulation (IER3, CCNG2, PER1), with up
regulation of transcription genes and cellular proliferation genes (FOS, EGR1,
MET, JMJD6) that are hypoxia-inducible. The potential clinical implications of
these results are related to the epidemiological findings of increased
susceptibility and expression of periodontitis with aging. More specifically the
findings describe that hypoxic stress may exist in aging gingival tissues before
documentation of clinical changes of periodontitis and, so, may provide an
explanatory molecular risk factor for an elevated capacity of the tissues to
express destructive processes in response to changes in the microbial biofilms
characteristic of a more pathogenic microbial challenge.
PMID- 29338079
TI - Nutrition Delivery and Growth Outcomes in Infants With Gastroschisis.
AB - BACKGROUND: We aimed to describe nutrient intake and growth in infants with
gastroschisis and identify factors associated with impaired growth. METHODS:
Retrospective study of neonates who underwent gastroschisis repair from 2010 to
2015. Nutrient intake and weight-for-age z scores (WAZ) were recorded. RESULTS:
Data from 60 eligible infants with median (Q1, Q3) gestational age of 36 weeks
(35, 37) and birth weight 2418 g (2098, 2665) were analyzed. Median WAZ decreased
from -0.71 (-1.08, -0.17) at birth to -1.08 (-1.58, -0.63) at discharge (P <
.001); 30% experienced a >1.0 decline in WAZ. Parenteral nutrition (PN) was
initiated soon after birth, and 14 (23%) patients had severe intestinal failure.
Fourteen patients (23%) experienced central line-associated bloodstream infection
(CLABSI) at a rate of 5.0 per 1000 catheter days. Factors independently
associated with lower discharge WAZ and greater WAZ decline were CLABSI (P = .02)
and prematurity (P = .02). By day 7, energy and protein intake were 90-100
kcal/kg/day and 3 g/kg/day, respectively. Median age to achieve enteral autonomy
was 36 days (22, 82). Atresias, CLABSI, prematurity, and staged closure were
associated with delayed enteral autonomy (P < .01). Among 34 patients with 1-year
follow-up, WAZ improved from -1.16 (-1.74, -0.65) at discharge to 0.19 (-0.80,
0.61) at 12 months (P < .001). CONCLUSION: Infants with gastroschisis are
dependent on PN and have a significant decline in WAZ during their hospital stay,
predicted by prematurity and CLABSI. Efforts to prevent CLABSI and optimize
enteral autonomy must be prioritized in this cohort.
PMID- 29338080
TI - Phase 1 trial evaluating cisplatin, gemcitabine, and veliparib in 2 patient
cohorts: Germline BRCA mutation carriers and wild-type BRCA pancreatic ductal
adenocarcinoma.
AB - BACKGROUND: A phase 1 trial was used to evaluate a combination of cisplatin,
gemcitabine, and escalating doses of veliparib in patients with untreated
advanced pancreatic ductal adenocarcinoma (PDAC) in 2 cohorts: a germline BRCA1/2
mutated (BRCA+) cohort and a wild-type BRCA (BRCA-) cohort. The aims were to
determine the safety, dose-limiting toxicities (DLTs), maximum tolerated dose,
and recommended phase 2 dose (RP2D) of veliparib combined with cisplatin and
gemcitabine and to assess the antitumor efficacy (Response Evaluation Criteria in
Solid Tumors, version 1.1) and overall survival. METHODS: Gemcitabine and
cisplatin were dosed at 600 and 25 mg/m2 , respectively, over 30 minutes on days
3 and 10 of a 21-day cycle. Four dose levels of veliparib were evaluated: 20
(dose level 0), 40 (dose level 1), and 80 mg (dose level 2) given orally twice
daily on days 1 to 12 and 80 mg given twice daily on days 1 to 21 (dose level 2A
[DL2A]). RESULTS: Seventeen patients were enrolled: 9 BRCA+ patients, 7 BRCA-
patients, and 1 patient with an unknown status. DLTs were reached at DL2A (80 mg
twice daily on days 1 to 21). Two of the 5 patients in this cohort (40%)
experienced grade 4 neutropenia and thrombocytopenia. Two grade 5 events occurred
on protocol. The objective response rate in the BRCA+ cohort was 7 of 9 (77.8%).
The median overall survival for BRCA+ patients was 23.3 months (95% confidence
interval [CI], 3.8-30.2 months). The median overall survival for BRCA- patients
was 11 months (95% CI, 1.5-12.1 months). CONCLUSIONS: The RP2D of veliparib was
80 mg by mouth twice daily on days 1 to 12 in combination with cisplatin and
gemcitabine; the DLT was myelosuppression. Substantial antitumor activity was
seen in BRCA+ PDAC. A randomized phase 2 trial is currently evaluating cisplatin
and gemcitabine with and without veliparib for BRCA+ PDAC (NCT01585805). Cancer
2018;124:1374-82. (c) 2018 American Cancer Society.
PMID- 29338081
TI - Nonsurgical premature menopause and reproductive implications in survivors of
childhood cancer: A report from the Childhood Cancer Survivor Study.
AB - BACKGROUND: Survivors of childhood cancer are at risk of nonsurgical premature
menopause (NSPM). To the authors' knowledge, risk factors for NSPM and its impact
on reproduction remain poorly defined. METHODS: The menopausal status of 2930
survivors diagnosed between 1970 and 1986 (median age, 6 years [range, birth-20
years]) who were aged > 18 years at the time of the current study (median age, 35
years [range, 18-58 years]) was compared with 1399 siblings. NSPM was defined as
the cessation of menses >=6 months in duration occurring 5 years after diagnosis
and before age 40 that was not due to pregnancy, surgery, or medications. Among
survivors, multivariable logistic regression identified risk factors for NSPM.
Pregnancy and live birth rates were compared between survivors with and without
NSPM. RESULTS: A total of 110 survivors developed NSPM (median age, 32 years
[range, 16-40 years]), with a prevalence at age 40 years of 9.1% (95% confidence
interval [95% CI], 4.9%-17.2%); the odds ratio (OR) was 10.5 (95% CI, 4.2-26.3)
compared with siblings. Independent risk factors included exposure to a
procarbazine dose >=4000 mg/m2 (OR, 8.96 [95% CI, 5.02-16.00]), any dose of
ovarian radiation (OvRT) (OvRT < 500 cGy: OR, 2.73 [95% CI, 1.33-5.61] and OvRT
>= 500 cGy: OR, 8.02 [95% CI, 2.81-22.85]; referent RT, 0), and receipt of a stem
cell transplantation (OR, 6.35; 95% CI, 1.19-33.93). Compared with survivors
without NSPM, those who developed NSPM were less likely to ever be pregnant (rate
ratio, 0.49; 95% CI, 0.27-0.80) or to have a live birth (rate ratio, 0.42; 95%
CI, 0.19-0.79) between ages 31 and 40 years. CONCLUSIONS: Survivors of childhood
cancer are at risk of NSPM associated with lower rates of live birth in their
30s. Those at risk should consider fertility preservation if they anticipate
delaying childbearing. Cancer 2018;124:1044-52. (c) 2018 American Cancer Society.
PMID- 29338082
TI - Racial/ethnic differences in thyroid cancer incidence in the United States, 2007
2014.
AB - BACKGROUND: Small tumor diagnostic tools including ultrasound-guided fine needle
aspiration (FNA) and computed tomography (CT) could be causing rising and
racially/ethnically different thyroid cancer incidence rates due to variable
overdiagnosis of indolent tumors. Papillary tumors and <40 mm tumors are most
likely to be overdiagnosed as indolent tumors by FNA and CT. METHODS: Age
adjusted incidence rates (AAIRs) for the years 2007-2014 were calculated for
race/ethnicity (white, Hispanic, Asian, African American, Native American) by
patient/tumor characteristics for microscopically confirmed malignant thyroid
cancer cases in the Surveillance, Epidemiology, and End Results Program 18
database (SEER 18; N = 93,607). Multivariate analysis determined cancer patients'
odds ratios of diagnosis with papillary thyroid carcinoma (vs other histologies)
and tumors <40 mm (vs >=40 mm). RESULTS: For both males and females, there were
statistically significant differences in incidence rates between race/ethnicity,
with whites having the highest AAIRs and African Americans the lowest AAIRs.
Among thyroid cancer patients, tumor size and histology differed significantly by
race and insurance coverage after controlling for age, sex, stage, and tumor
sequence. Non-whites with thyroid cancer (vs whites) were less associated with
small tumors (odds ratio [OR], 0.51-0.79; P < .0001). Medicaid and uninsured
patients with thyroid cancer were less associated with tumors <40 mm (OR, 0.55
0.71; 95% confidence interval [CI], 0.49-0.76) and papillary carcinoma (OR, 0.86;
95% CI, 0.80-0.93). CONCLUSION: The diagnosis of small tumors is occurring at
greater rates in whites (vs non-whites) and insured (vs Medicaid and uninsured)
patients; consequently, these groups may be vulnerable to unnecessary tests and
treatments or potentially aided by early detection. Guidelines that define
postdetection interventions may be needed to limit the overtreatment of indolent
and small papillary carcinomas. Cancer 2018;124:1483-91. (c) 2018 American Cancer
Society.
PMID- 29338084
TI - Importance of B cells to development of regulatory T cells and prolongation of
tissue allograft survival in recipients receiving autologous bone marrow
transplantation.
AB - We previously showed that congenic bone marrow transplantation (BMTx) post
myeloablation augmented tissue allograft survival in association with increased
regulatory T (Treg) cells of both host and bone marrow donor origin. Regulatory B
(Breg) cells can also modulate T-cell immunity and B cells may be implicated in
the development of Treg cells. Accordingly, we explored the effect of B-cell
depletion in vivo on augmented graft survival post BMTx. C57BL/6 mice received
BALB/c skin allografts followed 7 days later by myeloablation using
cyclophosphamide and busulphan. Mice then received T-cell-depleted bone marrow
from CD45.1 congenic donors, and ongoing immunosuppression with rapamycin (to day
28 after BMTx). Control mice received cyclophosphamide and busulphan followed by
rapamycin, but not congenic bone marrow. At different times post BMTx, mice
received B-cell-depleting antibody treatment, and the effect on both skin graft
survival, and induction of Treg cells was assessed. BMTx resulted in
significantly prolonged skin graft survival versus control mice, in association
with attenuated donor-specific alloreactivity relative to controls, increased
splenic Treg cells and significantly diminished anti-donor IgG. In mice receiving
infusion of B-depleting antibodies for 12 days from day 15 post BMTx, both graft
survival and Treg cell activity were diminished, particularly for functional Treg
cells of donor origin. Adoptive transfer of Breg cells from mice harvested at 15
days post BMTx prolonged survival in naive transplanted mice and increased Treg
cell levels. Thus, autologous BMTx augmentation of graft survival is dependent in
part upon a population of Breg cells that can modulate the function of donor
derived Treg cells.
PMID- 29338083
TI - Androgen-deprivation therapy, dementia, and cognitive dysfunction in men with
prostate cancer: How much smoke and how much fire?
AB - Androgen-deprivation therapy (ADT) remains the cornerstone of management for
patients with metastatic prostate cancer. Although the toxicities of ADT are well
established, there is increasing controversy surrounding the association between
cognitive dysfunction and the receipt of ADT, with some evidence suggesting an
increased risk of dementia. The authors conducted a literature search to identify
pertinent clinical studies in this field. This general review outlines the key
findings and discusses the relative strengths and weaknesses when drawing
conclusions about the risk of cognitive dysfunction or dementia with ADT use.
Cancer 2018;124:1326-34. (c) 2018 American Cancer Society.
PMID- 29338085
TI - The century experiment: the first twenty years of UC Davis' Mediterranean
agroecological experiment.
AB - The Century Experiment at the Russell Ranch Sustainable Agriculture Facility at
the University of California, Davis provides long-term agroecological data from
row crop systems in California's Central Valley starting in 1993. The Century
Experiment was initially designed to study the effects of a gradient of water and
nitrogen availability on soil properties and crop performance in ten different
cropping systems to measure tradeoffs and synergies between agricultural
productivity and sustainability. Currently systems include 11 different cropping
systems-consisting of four different crops and a cover crop mixture-and one
native grass system. This paper describes the long-term core data from the
Century Experiment from 1993-2014, including crop yields and biomass, crop
elemental contents, aerial-photo-based Normalized Difference Vegetation Index
data, soil properties, weather, chemical constituents in irrigation water, winter
weed populations, and operational data including fertilizer and pesticide
application amounts and dates, planting dates, planting quantity and crop
variety, and harvest dates. This data set represents the only known long-term set
of data characterizing food production and sustainability in irrigated and
rainfed Mediterranean annual cropping systems. There are no copyright
restrictions associated with the use of this dataset.
PMID- 29338086
TI - Cardiometabolic risk factors and survival after breast cancer in the Women's
Health Initiative.
AB - BACKGROUND: Few studies have examined the relationship between cardiometabolic
risk factors linked to metabolic syndrome and mortality among women with breast
cancer. METHODS: We used the Women's Health Initiative to evaluate the
relationship between cardiometabolic risk factors, including waist circumference
(WC), blood pressure, cholesterol level, and presence of type 2 diabetes, and
their relation with death from breast cancer, cardiovascular disease (CVD), and
other causes among 8641 women with local or regional stage invasive breast
cancer. Cox proportional hazards models were used to estimate hazard ratios, and
95% confidence intervals, adjusted for important predictors of survival. RESULTS:
After a median of 11.3 years, there were 2181 total deaths, 619 (28.4%) of which
were due to breast cancer. Most participants (55.7%) had at least 2
cardiometabolic risk factors, and 4.9% had 3 or 4. Having a larger number of risk
factors was associated with higher risk of CVD and other-cause mortality (P trend
< .001 for both), but not with breast cancer mortality (P trend = .86). Increased
WC was associated with a higher risk of CVD (hazard ratio [HR], 1.28; 95%
confidence interval [CI], 1.05-1.57) and other-cause mortality (HR, 1.32; 95% CI,
1.16-1.49) and only with a small and nonsignificant higher risk of breast cancer
mortality (HR, 1.19; 95% CI, 0.93-1.52). The results did not differ in analyses
stratified by race, hormone receptor status, or after an analysis of cases
diagnosed within 5 years after baseline. CONCLUSIONS: Among women with early
stage breast cancer, cardiometabolic risk factors are significantly associated
with cardiovascular and other-cause mortality, but not breast cancer mortality.
Cancer 2018;124:1798-807. (c) 2018 American Cancer Society.
PMID- 29338087
TI - Gabapentin prevents synaptogenesis between sensory and spinal cord neurons
induced by thrombospondin-4 acting on pre-synaptic Cav alpha2 delta1 subunits and
involving T-type Ca2+ channels.
AB - BACKGROUND AND PURPOSE: Nerve injury induces concurrent up-regulation of the
voltage-gated calcium channel subunit Cav alpha2 delta1 and the extracellular
matrix protein thrombospondin-4 (TSP4) in dorsal root ganglia and dorsal spinal
cord, leading to the development of a neuropathic pain state. Interactions of
these proteins promote aberrant excitatory synaptogenesis that contributes to
neuropathic pain state development through unknown mechanisms. We investigated
the contributions of Cav alpha2 delta1 subunits and TSP4 to synaptogenesis, and
the pathways involved in vitro, and whether treatment with gabapentin could block
this process and pain development in vivo. EXPERIMENTAL APPROACH: A co-culture
system of sensory and spinal cord neurons was used to study the contribution from
each protein to synaptogenesis and the pathway(s) involved. Anti-synaptogenic
actions of gabapentin were studied in TSP4-injected mice. KEY RESULTS: Only
presynaptic, but not postsynaptic, Cav alpha2 delta1 subunits interacted with
TSP4 to initiate excitatory synaptogenesis through a pathway modulated by T-type
calcium channels. Cav alpha2 delta1 /TSP4 interactions were not required for
maintenance of already formed synapses. In vivo, early, but not delayed,
treatment with low-dose gabapentin blocked this pathway and the development of
the pain state. CONCLUSIONS AND IMPLICATIONS: Cav alpha2 delta1 /TSP4
interactions were critical for the initiation, but not for the maintenance, of
abnormal synapse formation between sensory and spinal cord neurons. This process
was blocked by early, but was not reversed by delayed, treatment with gabapentin.
Early intervention with gabapentin may prevent the development of injury-induced
chronic pain, resulting from Cav alpha2 delta1 /TSP4-initiated abnormal synapse
formation. LINKED ARTICLES: This article is part of a themed section on Recent
Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other
articles in this section visit
http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.12/issuetoc.
PMID- 29338088
TI - Margins in breast cancer: How much is enough?
AB - The appropriate negative margin width for women undergoing breast-conserving
surgery for both ductal carcinoma in situ (DCIS) and invasive carcinoma is
controversial. This review examines the available data on the margin status for
invasive breast cancer and DCIS, and highlights the similarities and differences
in tumor biology and standard treatments that affect the local recurrence (LR)
risk and, therefore, the optimal surgical margin. Consensus guidelines support a
negative margin, defined as no ink on tumor, for invasive carcinoma treated with
breast-conserving therapy. Because of differences in the growth pattern and
utilization of systemic therapy, a margin of 2 mm has been found to minimize the
LR risk for women with DCIS undergoing lumpectomy and radiation therapy (RT).
Wider negative margins do not improve local control for DCIS or invasive
carcinoma when they are treated with lumpectomy and RT. Re-excision for negative
margins should be individualized, and the routine practice of performing
additional surgery to obtain a wider negative margin is not supported by the
literature. Cancer 2018;124:1335-41. (c) 2018 American Cancer Society.
PMID- 29338089
TI - Outcomes of patients diagnosed with carcinoma metastatic to the neck from an
unknown primary source and treated with intensity-modulated radiation therapy.
AB - BACKGROUND: There are few published studies to guide the treatment of carcinoma
metastatic to the neck from an unknown primary (CUP). In this regard, the
objective of the current study was to share the authors' current experience
treating patients with CUP using intensity-modulated radiation therapy (IMRT),
which principally targeted both sides of the neck, the nasopharynx, and the
oropharynx. METHODS: This was a retrospective study in which an institutional
database search was conducted to identify patients with CUP who received IMRT.
Data analysis included frequency tabulation, survival analysis, and multivariable
analysis. RESULTS: Two-hundred sixty patients met inclusion criteria. The most
common lymph node category was N2b (54%). IMRT volumes included the entire
pharyngolaryngeal mucosa in 78 patients, the nasopharynx and oropharynx in 167
patients, and treatment limited to the involved neck in 11 patients. Eighty-four
patients underwent neck dissections. The 5-year overall survival, regional
control, and distant metastases-free survival rates were 84%, 91%, and 94%,
respectively. Over 40% of patients had gastrostomy tubes during therapy, and 7%
patients were diagnosed with chronic radiation-associated dysphagia. Higher lymph
node burden was associated with worse disease-related outcomes, and in subgroup
analysis, patients with human papillomavirus-associated disease had better
outcomes. No therapeutic modality was statistically associated with either
disease-related outcomes or toxicity. CONCLUSIONS: Comprehensive IMRT with
treatment to both sides of the neck and to the oropharyngeal and nasopharyngeal
mucosa results in high rates of disease control and survival. The investigators
were unable to demonstrate that treatment intensification with chemotherapy or
surgery added benefit or excessive toxicity. Cancer 2018;124:1415-27. (c) 2018
American Cancer Society.
PMID- 29338090
TI - Influence of provider factors and race on uptake of breast cancer gene expression
profiling.
AB - BACKGROUND: Gene expression profiling (GEP) has been rapidly adopted for early
breast cancer and can aid in chemotherapy decision making. Study results
regarding racial disparities in testing are conflicting, and may reflect
different care settings. To the authors' knowledge, data regarding the influence
of provider factors on testing are scarce. METHODS: The authors used a statewide,
multipayer, insurance claims database linked to cancer registry records to
examine the impact of race and provider characteristics on GEP uptake in a cohort
of patients newly diagnosed with breast cancer between 2005 and 2012. Incidence
proportion models were used to examine the adjusted likelihood of testing. Models
were stratified by lymph node status (N0 vs N1). RESULTS: Among 11,958 eligible
patients, 23% of black and 26% of non-Hispanic white patients received GEP. Among
patients with N0 disease, black individuals were 16% less likely to receive
testing after adjustment for clinical factors and the provider's specialty and
volume of patients with breast cancer (95% confidence interval, 0.77-0.93).
Adjustment for provider characteristics did not attenuate the effect of race on
testing. Patients of middle-volume providers were more likely to be tested
compared with those with either high-volume or low-volume providers, whereas
patients seeing a medical oncologist were more likely to be tested compared with
those whose only providers were from surgical specialties. CONCLUSIONS: Provider
volume and specialty were found to be significant predictors of GEP use, but did
not explain racial disparities in testing. Further research concerning the key
contributors to lagging test use among black women is needed to optimize the
equitable use of GEPs and support personalized treatment decision making for all
patients. Cancer 2018;124:1743-51. (c) 2018 American Cancer Society.
PMID- 29338091
TI - Using Difference Scores to Inform Therapy Practice: Differences in Perceptions of
Attachment Behaviors between Partners in a Clinical Sample.
AB - Using clinically relevant research methodology, this study focuses on differences
(cross-partner difference scores) in perceptions of attachment behaviors
(emotional accessibility, responsiveness, and engagement) between partners in
couples therapy. In general, findings suggest that higher levels of self
enhancement attachment behaviors (participant perceives self as demonstrating
more attachment behaviors than the partner's ratings of the participant) are
associated with lower relationship satisfaction and greater relationship
instability. The association between attachment behavior difference scores and
measures of relationship health is mediated through partner perceived positive
communication. These results suggest that differences in perceptions between
partners' level of attachment behaviors are an important clinical construct for
therapy. As such, clinical recommendations for addressing self-enhancing
attachment behaviors, and the mediating role of positive communication, are
discussed with recommendations for researchers.
PMID- 29338092
TI - Delayed initial radioiodine therapy related to incomplete response in low- to
intermediate-risk differentiated thyroid cancer.
AB - OBJECTIVE: Whether the initiating time of radioiodine (RAI) therapy will affect
the clinical outcome in differentiated thyroid cancer (DTC) remains
controversial. The objective of this study was to evaluate the impact of RAI
therapy initiating time on response to initial therapy in low- to intermediate
risk DTC. METHODS: A total of 235 consecutive patients with low- to intermediate
risk DTC were retrospectively reviewed. According to the time interval between
thyroidectomy and RAI therapy, patients were divided into Group 1 (interval < 3
months, n = 187) and Group 2 (interval >= 3 months, n = 48). Response to RAI
therapy was evaluated as excellent, indeterminate, biochemical incomplete or
structural incomplete response (ER, IDR, BIR or SIR) with a median follow-up of
780 days. The univariate and multivariate analyses were further conducted to
identify factors associated with incomplete response (IR, including BIR and SIR).
RESULTS: Response to initial therapy was significantly different between 2 groups
(P < .05), after excluding the impact of other risk factors (age, gender,
histological type, status of T and N, RAI dose, thyrotropin, stimulated
thyroglobulin and follow-up time). A significantly higher IR rate (18.8% vs 4.3%,
P = .001) and a lower ER proportion (62.5% vs 78.1%, P = .027) were observed in
Group 2. By univariate analysis, both T status and N status, stimulated
thyroglobulin and time interval were significant risk factors for IR (P < .05).
Multivariate analysis demonstrated that the time interval was an independent risk
factor for IR (P = .008). CONCLUSIONS: Delayed initial RAI therapy (>=3 months
after thyroidectomy) related to incomplete response in low- to intermediate-risk
DTC.
PMID- 29338093
TI - Longitudinal Profiles of Metabolism and Bioenergetics Associated with Innate
Immune Hormonal Inflammatory Responses and Amino-Acid Kinetics in Severe Sepsis
and Systemic Inflammatory Response Syndrome in Children.
AB - BACKGROUND: Experimental data indicate that sepsis influences the mitochondrial
function and metabolism. We aim to investigate longitudinal bioenergetic,
metabolic, hormonal, amino-acid, and innate immunity changes in children with
sepsis. METHODS: Sixty-eight children (sepsis, 18; systemic inflammatory response
syndrome [SIRS], 23; healthy controls, 27) were enrolled. Plasma amino acids were
determined by high-performance liquid chromatography (HPLC); flow-cytometry
expressed as mean fluorescence intensity (MFI) of heat shock protein (HSP) levels
from monocytes (m) and neutrophils (n); resistin, adiponectin, and extracellular
(e) HSPs evaluated by ELISA; ATP levels in white blood cells by luciferase
luminescent assay; lipid peroxidation products (TBARS) by colorimetric test;
nitrite and nitrate levels by chemiluminescent assay; biliverdin reductase (BVR)
activity by enzymatic assay; and energy-expenditure (EE) by E-COVX. RESULTS:
Resistin, eHSP72, eHSP90alpha, and nitrate were longitudinally higher in sepsis
compared with SIRS (p<0.05); mHSP72, nHSP72, VO2 , VCO2 , EE, and metabolic
pattern were repressed in sepsis compared with SIRS (p<0.05). Septic patients had
lower ATP and TBARS compared with controls on day 1, lower ATP compared with SIRS
on day 3 (p<0.05), but higher levels of BVR activity. Sepsis exhibited higher
phenylalanine levels on day 1, serine on day 3; lower glutamine concentrations on
days 3 and 5 (p<0.05). Resistin, inversely related to ATP, was independently
associated with sepsis, along with mHSP72 and eHSP90alpha (p<0.05); TBARS and VO2
were independently associated with organ failure (p<0.05)). Septic nonsurvivors
had malnutrition, persistently repressed metabolism, mHSP72, and induced resistin
and adiponectin (p<0.05). CONCLUSIONS: A pattern of early longitudinal induction
of metabolic-hormones and eHSP72/HSP90alpha, repression of bioenergetics and
innate immunity, hypo-metabolism, and amino-acid kinetics changes discriminate
sepsis from SIRS; malnutrition, hypo-metabolism, and persistently increased
resistin and adiponectin are associated with poor outcome.
PMID- 29338094
TI - Postnatal experiences, knowledge and perceptions of women with gestational
diabetes.
AB - AIM: Women with gestational diabetes mellitus (GDM) are at increased risk of Type
2 diabetes. This study aimed to explore experiences, knowledge and perceptions of
women with GDM to inform the design of interventions to prevent or delay Type 2
diabetes. METHODS: Semi-structured interviews were carried out with 16 women with
GDM who were recruited from a clinic in one Scottish health board. A framework
approach was used to manage and analyse data according to themes informed by
psychological theory (self-regulation model and theory of planned behaviour).
RESULTS: GDM is not seen as an important, or even real diagnosis among some
women, and this perception may result from the perceived minimal impact of GDM on
their lives. Some women did experience a bigger emotional and practical impact.
Knowledge and understanding of Type 2 diabetes was poor in general and many women
were unconcerned about their future risk. Lower concern appeared to be linked to
a lower perceived impact of GDM. Lifestyle changes discussed by women mostly
related to diet and were motivated primarily by concern for their baby's health.
Many women did not maintain these changes postnatally, reporting significant
barriers. CONCLUSIONS: This study has suggested potential avenues to be explored
in terms of content, timing and potential recipients of interventions.
Educational interventions postnatally could address illness perceptions in women
with GDM and redress the situation where lack of aftercare downplays its
seriousness. For lifestyle interventions, the child's health could be used as a
motivator within the context of later joint or family interventions.
PMID- 29338095
TI - Patient-controlled tissue collection for genetic testing after early pregnancy
loss: A pilot study.
AB - OBJECTIVE: To determine how frequently and effectively products of conception can
be obtained among women pursuing medical management of early pregnancy loss.
METHODS: This pilot study was conducted to assess products of conception recovery
outcomes for participants opting for medical management compared with women
opting for surgical aspiration A tissue-collection kit was provided to women
opting for medical management. Outcome measures included successful collection of
products of conception, quantity and integrity of DNA, and participant
satisfaction with the process. RESULTS: Tissue was collected from 19 of 22
participants in the medical management group (84%) and 39 participants (100%) in
the surgical management group (P = .02). DNA yield and integrity were similar
among both groups (P = .03 and P = .003, respectively). Participants in the
medical group reported a high comfort level with the kit and the process of
tissue collection. CONCLUSIONS: Medical management of a missed abortion followed
by patient-controlled collection of products of conception for subsequent
cytogenetic analysis is well tolerated and highly effective. This methodology may
reduce the need for surgical management, empower women to have more agency in
their medical decisions, and increase access to genetic testing.
PMID- 29338096
TI - Controlling Selectivity in Aliphatic C-H Oxidation through Supramolecular
Recognition.
AB - Aliphatic C-H oxidation is the most straightforward approach to functionalize
hydrocarbon skeletons. The main challenge of this reaction is the control of site
selectivity, given the multiple C-H bonds present in any organic molecule.
Natural enzymes elegantly solve this problem through the interplay of different
interactions that geometrically orient the substrate to expose a single C-H bond
to the active unit, thus overriding intrinsic reactivity patterns. A combination
of molecular catalysts and supramolecular receptors can be a promising way to
replicate such control. This strategy indeed unlocks hydroxylation of C-H bonds
that are not accessible with conventional methodologies, in which the selectivity
is dictated by the geometry of the substrate-receptor adduct. Herein, we review
the reports of recognition-driven C-H oxidation reactions and highlight the key
design principles that inspired these works.
PMID- 29338097
TI - Synthesis of Multifunctional Spirocyclic Azetidines and Their Application in Drug
Discovery.
AB - The synthesis of multifunctional spirocycles was achieved from common cyclic
carboxylic acids (cyclobutane carboxylate, cyclopentane carboxylate, l-proline,
etc.). The whole sequence included only two chemical steps-synthesis of
azetidinones, and reduction into azetidines. The obtained spirocyclic amino acids
were incorporated into a structure of the known anesthetic drug Bupivacaine. The
obtained analogues were more active and less toxic than the original drug. We
believe that this discovery will lead to a wide use of spirocyclic building
blocks in drug discovery in the near future.
PMID- 29338099
TI - Establishing the Critical Role of Oriented Aggregation in Molecular Solid State
Fluorescence Enhancement.
AB - The general occurrence of fluorescence emission quenching in molecular aggregates
is circumvented in select classes of molecules. This has largely been attributed
to the rigidification of the molecule and its environment, which hinders non
radiative excited state energy loss through structural relaxation; since such an
effect should in principle apply to most aggregates and crystals, there must
clearly be other critical factors that make the select molecules exceptional.
Discovery of three crystalline structures of a new push-pull molecule in its
enantiomorphic and racemic forms, exhibiting not only very high, but distinctly
different solid state fluorescence enhancements, has now allowed a systematic
investigation of the role of intramolecular and intermolecular excited state
energy loss pathways. Crystallographic, spectroscopic and computational
investigations provide a detailed appraisal of the assembly patterns in the
crystals, and rigorous establishment of an inverse correlation between
intermolecular energy transfer and solid state fluorescence. The study provides a
clear visualization of the critical role of oriented molecular aggregation in
solid state fluorescence efficiency enhancement.
PMID- 29338098
TI - Increase in motility and invasiveness of MCF7 cancer cells induced by nicotine is
abolished by melatonin through inhibition of ERK phosphorylation.
AB - Through activation of the ERK pathway, nicotine, in both normal MCF-10A and low
malignant breast cancer cells (MCF7), promotes increased motility and
invasiveness. Melatonin antagonizes both these effects by inhibiting almost
completely ERK phosphorylation. As melatonin has no effect on nonstimulated
cells, it is likely that melatonin can counteract ERK activation only downstream
of nicotine-induced activation. This finding suggests that melatonin hampers ERK
phosphorylation presumably by targeting a still unknown intermediate factor that
connects nicotine stimulation to ERK phosphorylation. Furthermore, downstream of
ERK activation, melatonin significantly reduces fascin and calpain activation
while restoring normal vinculin levels. Melatonin also counteracts nicotine
effects by reshaping the overall cytoskeleton architecture and abolishing
invasive membrane protrusion. In addition, melatonin decreases nicotine-dependent
ROCK1/ROCK2 activation, thus further inhibiting cell contractility and motility.
Melatonin actions are most likely attributable to ERK inhibition, although
melatonin could display other ERK-independent effects, namely through a direct
modulation of additional molecular and structural factors, including coronin,
cofilin, and cytoskeleton components.
PMID- 29338100
TI - Fixing the Conformation of Calix[4]arenes: When Are Three Carbons Not Enough?
AB - Calix[4]arenes are unique macrocycles that through judicious functionalisation at
the lower rim can be either fixed in one of four conformations or remain
conformationally flexible. Introduction of propynyl or propenyl groups
unexpectedly provides a new possibility; a unidirectional conformational switch,
with the 1,3-alternate and 1,2-alternate conformers switching to the partial cone
conformation, whilst the cone conformation is unchanged, under standard
experimental conditions. Using 1 H NMR kinetic studies, rates of switching have
been shown to be dependent on the starting conformation, upper-rim substituent,
where reduction in bulk enables faster switching, solvent and temperature with
1,2-alternate conformations switching fastest. Ab initio calculations (DFT)
confirmed the relative stabilities of the conformations and point towards the
partial cone conformer being the most stable of the four. The potential impact on
synthesis through the "click" reaction has been investigated and found not to be
significant.
PMID- 29338101
TI - Mechanochromic Polymers That Turn Green Upon the Dissociation of
Diarylbibenzothiophenonyl: The Missing Piece toward Rainbow Mechanochromism.
AB - Mechanochromic polymers, that is, polymers sensitive to mechanical impact,
promise great potential for applications in damage sensors. In particular,
radical-type mechanochromic polymers, which produce colored radical species in
response to mechanical stress, may enable not only the visualization of
mechanical stress, but also its quantitative evaluation by electron paramagnetic
resonance analysis. Herein, a radical-type mechanochromic polymer that exhibits a
color change from white to green upon dissociation of a diarylbibenzothiophenonyl
moiety at the mid-point of a polystyrene chain is presented, and its
mechanochromic behavior is examined. Mechanochromic materials that show a variety
of colors ("rainbow colors") in response to mechanical stress were prepared by
simply mixing radical-type mechanochromic polymers of primary colors.
PMID- 29338102
TI - Circulating Serum 25-Hydroxyvitamin D Levels and Bone Mineral Density: Mendelian
Randomization Study.
AB - There is considerable discussion of the importance for increased serum 25
hydroxyvitamin D (S-25OHD) concentration associated with adequacy for bone
health. Accordingly, whether long-term high S-25OHD concentration in general
positively affects bone mineral density (BMD) is uncertain. We used a Mendelian
randomization design to determine the association between genetically increased S
25OHD concentrations and BMD. Five single-nucleotide polymorphisms (SNPs) in or
near genes encoding enzymes and carrier proteins involved in vitamin D synthesis
or metabolism were used as instrumental variables to genetically predict 1
standard deviation increase in S-25OHD concentration. Summary statistics data for
the associations of the S-25OHD-associated SNPs with dual-energy X-ray
absorptiometry (DXA)-derived femoral neck and lumbar spine BMD were obtained from
the Genetic Factors for Osteoporosis (GEFOS) Consortium (32,965 individuals) and
ultrasound-derived heel estimated BMD from the UK Biobank (142,487 individuals).
None of the SNPs were associated with BMD at Bonferroni-corrected significance
level, but there was a suggestive association between rs6013897 near CYP24A1 and
femoral neck BMD (p = 0.01). In Mendelian randomization analysis, genetically
predicted 1 standard deviation increment of S-25OHD was not associated with
higher femoral neck BMD (SD change in BMD 0.02; 95% confidence interval [CI]
0.03 to 0.07; p = 0.37), lumbar spine BMD (SD change in BMD 0.02; 95% CI -0.04 to
0.08; p = 0.49), or estimated BMD (g/cm2 change in BMD -0.03; 95% CI -0.05 to
0.01; p = 0.02). This study does not support a causal association between long
term elevated S-25OHD concentrations and higher BMD in generally healthy
populations. These results suggest that more emphasis should be placed on the
development of evidence-based cut-off points for vitamin D inadequacy rather than
a general recommendation to increase S-25OHD. (c) 2018 American Society for Bone
and Mineral Research.
PMID- 29338104
TI - Organotin Dyes Bearing Anionic Boron Clusters as Cell-Staining Fluorescent
Probes.
AB - Within the cell nucleus, in the nucleoli, ribosomal RNAs are synthesized and
participate in several biological processes. To better understand nucleoli
related processes, their visualization is often required, for which specific
markers are needed. Herein, we report the design of novel fluorescent organotin
compounds derived from 4-hydroxy-N'-((2-hydroxynaphthalen-1
yl)methylene)benzohydrazide and their cytoplasm and nucleoli staining of B16F10
cells in vitro. Tin compounds bearing an aliphatic carbon chain (-C12 H25 ) and
an electron-donating group (-OH) were prepared, and the latter could be
derivatized to bear the boron cluster anions [B12 H12 ]2- and [3,3'-Co(1,2-C2 B9
H11 )2 ]- (COSAN). All of the conjugates have been fully characterized and their
luminescence properties have been assessed. In general, they show good quantum
yields in solution (24-49 %), those for the COSAN derivatives being lower.
Remarkably, the linking of [B12 H12 ]2- and COSAN to the complexes made them more
soluble, without being detrimental to their luminescence properties. Living
B16F10 cells were treated with all of the compounds to determine their
fluorescence staining properties; the compounds bearing the aliphatic chain
showed a reduced staining capacity due to the formation of aggregates. Notably,
the complexes bearing different boron clusters showed different staining effects;
those bearing [B12 H12 ]2- showed extraordinary staining of the nucleoli and
cytoplasm, whereas those bearing COSAN were only detected in the cytoplasm. The
remarkable fluorescence staining properties shown by these organotin compounds
make them excellent candidates for fluorescence bioimaging in vitro.
PMID- 29338105
TI - Multiple sclerosis: long-term outcomes in ethnic minorities. Analysis of a UK
population-based registry.
AB - BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is most frequent in Caucasian
populations. However, studies of MS in other ethnic groups may offer unique
insights into genetic and environmental influences on the disease, and data on
long-term outcomes in these patients is limited. In this work clinical features
and time to disability milestones were investigated in ethnic minority (EM)
patients with MS in a UK population and comparisons were made to a Caucasian
cohort from the same region. METHODS: In all, 1949 MS patients (1866 Caucasian,
83 EM) were identified from a regional disease registry. Cox proportional hazards
regression was used to analyse the time to Expanded Disability Status Scale
(EDSS) 3.0, 4.0 and 6.0. RESULTS: Ethnic minority patients were younger at
disease onset (28.6 years vs. 32.8 years, P = 0.001), and primary progressive MS
was less common (EM 4.8%, Caucasian 11.6%, P = 0.03). After correction for
clinical variables, ethnicity was associated with time to EDSS 3.0 [EM: hazard
ratio (HR) 1.75, P < 0.0001] and 4.0 (HR 1.46, P = 0.03), but not 6.0 (HR 1.5, P
= 0.05). CONCLUSIONS: Ethnic minority patients reach early levels of fixed
disability more rapidly than Caucasian patients, but this effect diminishes at
later stages of the disease. This has implications for clinical management of
these patients.
PMID- 29338106
TI - Morning hypertension in Asian populations.
PMID- 29338103
TI - Interrogating Protein Phosphatases with Chemical Activity Probes.
AB - Protein phosphatases, while long overlooked, have recently become appreciated as
drivers of both normal- and disease-associated signaling events. As a result, the
spotlight is now turning torwards this enzyme family and efforts geared towards
the development of modern chemical tools for studying these enzymes are well
underway. This Minireview focuses on the evolution of chemical activity probes,
both optical and covalent, for the study of protein phosphatases. Small-molecule
probes, global monitoring of phosphatase activity through the use of covalent
modifiers, and targeted fluorescence-based activity probes are discussed. We
conclude with an overview of open questions in the field and highlight the
potential impact of chemical tools for studying protein phosphatases.
PMID- 29338107
TI - How often is the diagnosis of the permanent vegetative state incorrect? A review
of the evidence.
AB - Some research suggests that 40% of people in the vegetative state are
misdiagnosed. This review investigates the frequency, nature and causes of
reported misdiagnosis of patients in the vegetative state, focusing on the nature
of the error. It is a systematic review of all relevant literature, using
references from key papers identified. The data are summarized in tables. Five
clinical studies of the rate of misdiagnosis in practice were identified,
encompassing 236 patients in the vegetative state of whom 80 (34%) were
reclassified as having some awareness, often minimal. The studies often included
patients in the recovery phase after acute injury, and were poorly reported. Five
systematic reviews of signs and technologically based neurophysiological tests
were identified, and they showed that most studies were small, lacked accurate or
important details, and were subject to bias. Studies were not replicated. Many
signs and tests did not differ between people in the vegetative state and in the
minimally conscious state, and those that did were unable to diagnose an
individual patient. The few single case reports suggest that failure to ensure an
accurate diagnosis of the underlying neurological damage and dysfunction could,
rarely, lead to significant misdiagnosis usually in patients who had brain-stem
damage with little thalamic or cortical damage. Significant misdiagnosis of
awareness, with an apparently 'vegetative' patient having good awareness, is
rare. Careful neurological assessment of the cause and routine measurement of
awareness using the Coma Recovery Scale - Revised should further reduce mistakes.
PMID- 29338108
TI - The timing of liver resection in patients with colorectal cancer and synchronous
liver metastases: a population-based study of current practice and survival.
AB - AIM: There is uncertainty regarding the optimal sequence of surgery for patients
with colorectal cancer (CRC) and synchronous liver metastases. This study was
designed to describe temporal trends and inter-hospital variation in surgical
strategy, and to compare long-term survival in a propensity score-matched
analysis. METHOD: The National Bowel Cancer Audit dataset was used to identify
patients diagnosed with primary CRC between 1 January 2010 and 31 December 2015
who underwent CRC resection in the English National Health Service. Hospital
Episode Statistics data were used to identify those with synchronous liver
limited metastases who underwent liver resection. Survival outcomes of propensity
score-matched groups were compared. RESULTS: Of 1830 patients, 270 (14.8%)
underwent a liver-first approach, 259 (14.2%) a simultaneous approach and 1301
(71.1%) a bowel-first approach. The proportion of patients undergoing either a
liver-first or simultaneous approach increased over the study period from 26.8%
in 2010 to 35.6% in 2015 (P < 0.001). There was wide variation in surgical
approach according to hospital trust of diagnosis. There was no evidence of a
difference in 4-year survival between the propensity score-matched cohorts
according to surgical strategy: bowel first vs simultaneous [hazard ratio (HR)
0.92 (95% CI: 0.80-1.06)] or bowel first vs liver first [HR 0.99 (95% CI: 0.82
1.19)]. CONCLUSION: There is evidence of wide variation in surgical strategy in
dealing with CRC and synchronous liver metastases. In selected patients, the
simultaneous and liver-first strategies have comparable long-term survival to the
bowel-first approach.
PMID- 29338110
TI - Is it time to utilize measurement of arterial stiffness to identify and reduce
the risk of cognitive impairment?
PMID- 29338109
TI - Fused-Ring Formation by an Intramolecular "Cut-and-Sew" Reaction between
Cyclobutanones and Alkynes.
AB - The development of a catalytic intramolecular "cut-and-sew" transformation
between cyclobutanones and alkynes to construct cyclohexenone-fused rings is
described herein. The challenge arises from the need for selective coupling at
the more sterically hindered proximal position, and can be addressed by using an
electron-rich, but less bulky, phosphine ligand. The control experiment and 13 C
labelling study suggest that the reaction may start with cleavage of the less
hindered distal C-C bond of cyclobutanones, followed by decarbonylation and CO
reinsertion to enable Rh insertion at the more hindered proximal position.
PMID- 29338111
TI - The exaggerated blood pressure response to exercise in the sub-acute phase after
stroke is not affected by aerobic exercise.
AB - The prevalence of an exaggerated exercise blood pressure (BP) response is unknown
in patients with subacute stroke, and it is not known whether an aerobic exercise
program modulates this response. The authors randomized 53 patients (27 women)
with subacute stroke to 12 weeks of twice-weekly aerobic exercise (n = 29) or to
usual care without scheduled physical exercise (n = 24). At baseline, 66% of the
patients exhibited an exaggerated exercise BP response (peak systolic BP >=210 mm
Hg in men and >=190 mm Hg in women) during a symptom-limited ergometer exercise
test. At follow-up, patients who had been randomized to the exercise program
achieved higher peak work rate, but peak systolic BP remained unaltered. Among
patients with a recent stroke, it was common to have an exaggerated systolic BP
response during exercise. This response was not altered by participation in a 12
week program of aerobic exercise.
PMID- 29338112
TI - Benefits and pitfalls of sacubitril/valsartan treatment in patients with
hypertension.
PMID- 29338113
TI - Efficacy and safety of sacubitril/valsartan in patients with essential
hypertension uncontrolled by olmesartan: A randomized, double-blind, 8-week
study.
AB - A majority of patients with hypertension fail to achieve blood pressure (BP)
control despite treatment with commonly prescribed drugs. This randomized, double
blind phase III trial assessed the superiority of sacubitril/valsartan 200 mg
(97/103 mg) to continued olmesartan 20 mg in reducing ambulatory systolic BP
after 8-week treatment in patients with mild to moderate essential hypertension
uncontrolled with olmesartan 20 mg alone. A total of 376 patients were randomized
to receive either sacubitril/valsartan (n = 188) or olmesartan (n = 188).
Superior reductions in 24-hour mean ambulatory systolic BP were observed in the
sacubitril/valsartan group vs the olmesartan group (-4.3 mm Hg vs -1.1 mm Hg, P <
.001). Reductions in 24-hour mean ambulatory diastolic BP and pulse pressure and
office systolic BP and diastolic BP were significantly greater with
sacubitril/valsartan vs olmesartan (P < .014). A greater proportion of patients
achieved BP control with sacubitril/valsartan vs olmesartan. The overall
incidence of adverse events was comparable between the groups. Compared with
continued olmesartan, sacubitril/valsartan was more effective and generally safe
in patients with hypertension uncontrolled with olmesartan 20 mg.
PMID- 29338114
TI - Divergent Pathways Involving 1,3-Dipolar Addition and N-N Bond Splitting of an
Organic Azide across a Zirconium Methylidene.
AB - The zirconium methylidene (PNP)Zr=CH2 (OAr) (1) reacts with N3 Ad to give two
products (PNP)Zr=NAd(OAr) (2) and (PNP)Zr(eta2 -N=NAd)(N=CH2 )(OAr) (3), both
resulting from a common cycloaddition intermediate (PNP)Zr(CH2 N3 Ad)(OAr) (A).
Using a series of control experiments in combination with DFT calculations, it
was found that 2 results from a nitrene by a carbene metathesis reaction in which
N2 acts as a delivery vehicle and forms N2 CH2 as a side product. In the case of
3, N-N bond splitting of the azide at the alpha-position allowed the isolation of
a rare example of a parent ketimide complex of zirconium. Isotopic labeling
studies and solid-state X-ray analysis are presented for 2 and 3, in addition to
an independent synthesis for the former.
PMID- 29338115
TI - Statin use and vitreoretinal surgery: Findings from a Finnish population-based
cohort study.
AB - PURPOSE: Vitreoretinal (VR) surgery is the third most common intraocular surgery
after refractive and cataract surgery. The impact of statin therapy on VR surgery
outcomes remains unclear, despite a potentially beneficial effect. We explored
the association of preoperative statin therapy and the need for revitrectomy
after primary vitrectomy. METHODS: Our historical, population-based, register
based, VR surgery cohort consisted of 5709 patients operated in a tertiary,
academic referral hospital in Finland, during 2008-2014, covering 6.5 years.
Subgroup analysis was performed as follows: eyes operated due to (i)
rhegmatogenous retinal detachment (RRD), (ii) VR interface diseases (macular
pucker/hole), (iii) diabetic maculopathy or proliferative retinopathy, (iv)
vitreous haemorrhage, (v) lens subluxation, (vi) vitreous opacities or (vii)
other VR indication. The primary end-point event was revitrectomy during a
postoperative follow-up period of 1 year due to retinal redetachment, vitreous
rehaemorrhage, postoperative endophthalmitis, recurrent pucker or unclosed
macular hole. RESULTS: Rhegmatogenous retinal detachment (RRD) was the second
most frequent indication of VR surgery, including 1916 patients, with 305 re
operations with rate 0.20 (95% CI 0.18-0.23) per person-year. Statin treatment in
time of operation was associated with lower risk of re-operation according to
relative scale (incidence rate ratio 0.72, 95% CI 0.53-0.97), but not in absolute
scale (incidence rate difference -0.58, 95% CI -4.30 to 3.15 for 100 person
years). No association with statin therapy and vitrectomy outcome was observed in
the other VR subgroups. CONCLUSION: Use of statin treatment was associated with a
28% lower risk of revitrectomy in patients operated due to RRD. Further
randomized clinical trials are highly warranted.
PMID- 29338116
TI - Carbon Dioxide Promotes Dehydrogenation in the Equimolar C2 H2 -CO2 Reaction to
Synthesize Carbon Nanotubes.
AB - The equimolar C2 H2 -CO2 reaction has shown promise for carbon nanotube (CNT)
production at low temperatures and on diverse functional substrate materials;
however, the electron-pushing mechanism of this reaction is not well
demonstrated. Here, the role of CO2 is explored experimentally and theoretically.
In particular, 13 C labeling of CO2 demonstrates that CO2 is not an important C
source in CNT growth by thermal catalytic chemical vapor deposition. Consistent
with this experimental finding, the adsorption behaviors of C2 H2 and CO2 on a
graphene-like lattice via density functional theory calculations reveal that the
binding energies of C2 H2 are markedly higher than that of CO2 , suggesting the
former is more likely to incorporate into CNT structure. Further, H-abstraction
by CO2 from the active CNT growth edge would be favored, ultimately forming CO
and H2 O. These results support that the commonly observed, promoting role of CO2
in CNT growth is due to a CO2 -assisted dehydrogenation mechanism.
PMID- 29338117
TI - Nestin expression in primary and metastatic uveal melanoma - possible biomarker
for high-risk uveal melanoma.
AB - PURPOSE: Nestin, a member of the intermediate filament protein family, has been
described as a putative cancer stem cell marker (CSC) in uveal melanoma and poor
prognostic factor in a variety of tumours, including cutaneous melanoma. In this
study, we examined the expression of nestin in primary (PUM) and metastatic uveal
melanoma (MUM) samples, and correlated the findings with histological, clinical
and survival data. METHODS: Nestin expression was assessed by
immunohistochemistry in 141 PUM and 26 MUM samples; 11 PUM cases were matched
with their corresponding metastases. The percentage of tumour cells expressing
nestin was scored by three independent observers. Statistical analysis of all
data was performed with SPSS. RESULTS: Nestin expression was identified in both
the cytoplasm and membrane of UM cells. Increased expression of nestin in PUM
samples was associated with known poor prognostic parameters, including
epithelioid cell morphology (p < 0.001), closed loops (p = 0.001), higher mitotic
count (p < 0.001), monosomy 3 (p = 0.007) and chromosome 8q gain (p < 0.001).
Primary uveal melanoma (PUM) with nestin expression levels above a cut-off value
of 10% [as determined by receiver operating characteristic (ROC) analysis] was
associated with a significantly reduced survival time (Log-rank, p = 0.002). In
MUM, a higher percentage of nestin-positive tumour cells combined with poor
prognostic markers in the PUM led to a shorter survival time following the
development of metastases. CONCLUSION: In conclusion, increased nestin expression
in PUM is a predictor of a tumour phenotype associated with metastatic
progression and reduced survival time at onset of metastasis.
PMID- 29338118
TI - Impact of quality of research on patient outcomes in the Institute of Medicine
2013 report on dietary sodium.
AB - The 2013 Institute of Medicine report entitled "Sodium Intake in Populations:
Assessment of Evidence" found inconsistent evidence of health benefit with
dietary sodium intake <2300 mg/d. Different studies reported benefit and harm of
population dietary intake <2300 mg/d. The Institute of Medicine committee,
however, did not assess whether the methodology used in each of the studies was
appropriate to examine dietary sodium and health outcomes. This review
investigates the association of methodological rigor and outcomes of studies in
the Institute of Medicine report. For the 13 studies that met all methodological
criteria, nine found a detrimental impact of high sodium consumption on health,
one found a health benefit, and in three the effect was unclear (P = .068). For
the 22 studies that failed to meet all criteria, 11 showed a detrimental impact,
four a health benefit, and seven had unclear effects from increasing dietary
sodium (P = .42).
PMID- 29338119
TI - Management of morning hypertension: a consensus statement of an Asian expert
panel.
AB - Morning blood pressure (BP) surge is an important aspect of hypertension
research. Morning BP monitoring could be a clinically relevant concept in the
therapeutic management of hypertension and in the prevention of cardiovascular
complications by defining and treating morning hypertension. Because
antihypertensive medication is often taken in the morning, uncontrolled morning
BP during the trough effect hours could be a hallmark of inadequate choice of
antihypertensive regimen, such as the use of short- or intermediate-acting drugs,
underdosing of drugs, or no use or underuse of combination therapy. To improve
the management of hypertension in general and morning hypertension in particular,
long-acting antihypertensive drugs should be used in appropriate, often full
dosages and in proper combinations. The clinical usefulness of antihypertensive
drugs with specific mechanisms for morning BP or split or timed dosing of long
acting drugs in controlling morning BP remains under investigation.
PMID- 29338120
TI - The association between different features of sleep-disordered breathing and
blood pressure: A cross-sectional study.
AB - Sleep disordered breathing (SDB) is highly prevalent in patients with high blood
pressure (BP). Severity of SDB can be evaluated by the number of apneas and
hypopneas per hour (AHI) or by measures of hypoxia. The objective of this study
was to assess the association between different measures of SDB and BP. In 134
consecutive patients, polygraphy was performed to determine the AHI. Pulse
oximetry was used to determine hypoxemic burden (time below 90% oxygen saturation
[T90] and hypoxia load [HL], representing the integrated area above the curve of
desaturation). AHI did not correlate with systolic and diastolic BP or pulse
pressure. In contrast, HL correlated with pulse pressure during the day (P = .01)
and night (P = .0034) before and after adjustment for body mass index. The
correlation between systolic BP and HL at night disappeared following adjustment
for body mass index. This study generates the hypothesis that nocturnal hypoxemic
burden may represent a suitable marker of BP pattern and a potential treatment
target in hypertensive patients.
PMID- 29338121
TI - Does Confucianism allow for body donation?
AB - Confucianism has been widely perceived as a major moral and cultural obstacle to
the donation of bodies for anatomical purposes. The rationale for this is the
Confucian stress on xiao (filial piety), whereby individuals' bodies are to be
intact at death. In the view of many, the result is a prohibition on the donation
of bodies to anatomy departments for the purpose of dissection. The role of
dissection throughout the development of anatomy within a Confucian context is
traced, and in contemporary China the establishment of donation programs and the
appearance of memorial monuments is noted. In reassessing Confucian attitudes,
the stress laid on a particular interpretation of filial piety is questioned, and
an attempt is made to balance this with the Confucian emphasis on a moral duty to
those outside one's immediate family. The authors argue that the fundamental
Confucian norm ren (humaneness or benevolence) allows for body donation as people
have a moral duty to help others. Moreover, the other central Confucian value, li
(rites), offers important insights on how body donation should be performed as a
communal activity, particularly the necessity of developing ethically and
culturally appropriate rituals for body donation. In seeking to learn from this
from a Western perspective, it is contended that in all societies the voluntary
donation of bodies is a deeply human activity that is to reflect the
characteristics of the community within which it takes place. This is in large
part because it has educational and personal repercussions for students. Anat Sci
Educ 11: 525-531. (c) 2018 American Association of Anatomists.
PMID- 29338122
TI - NO, CO and H2 S: What about gasotransmitters in fish and amphibian heart?
AB - The gasotransmitters nitric oxide (NO), carbon monoxide (CO), and hydrogen
sulphide (H2 S), long considered only toxicant, are produced in vivo during the
catabolism of common biological molecules and are crucial for a large variety of
physiological processes. Mounting evidence is emerging that in poikilotherm
vertebrates, as in mammals, they modulate the basal performance of the heart and
the response to stress challenges. In this review, we will focus on teleost fish
and amphibians to highlight the evolutionary importance in vertebrates of the
cardiac control elicited by NO, CO and H2 S, and the conservation of the
intracellular cascades they activate. Although many gaps are still present due to
discontinuous information, we will use examples obtained by studies from our and
other laboratories to illustrate the complexity of the mechanisms that, by
involving gasotransmitters, allow beat-to-beat, short-, medium- and long-term
cardiac homoeostasis. By presenting the latest data, we will also provide a
framework in which the peculiar morpho-functional arrangement of the teleost and
amphibian heart can be considered as a reference tool to decipher cardiac
regulatory networks which are difficult to explore using more conventional
vertebrates, such as mammals.
PMID- 29338123
TI - Choroidal thickness and myopia in relation to physical activity - the CHAMPS Eye
Study.
AB - PURPOSE: To describe the relationship between choroidal thickness (CT) and myopia
in relation to physical activity (PA) in a population-based child cohort.
METHODS: In a prospective study of 307 children from the CHAMPS Study Denmark, we
used objective data from GT3X accelerometer worn at four periods between 2009 and
2015 to determine the amount and intensity of PA. Intensity was estimated as
counts/minutes, and cut-off points were defined at four intensity levels. Eye
examinations were performed in 2015 and included autorefraction in cycloplegia,
axial length (AL) by biometric and fovea-centred enhanced depth imaging optical
coherence tomography. By a semi-automated method, we measured the CT at 17
targets per eye representing anatomically different locations (subfoveal, 1 and 3
millimetre in each direction of fovea). RESULTS: Mean age at the eye examination
was 15.4 +/- 0.7 years. The mean AL was 23.5 +/- 0.9 mm, and the mean subfoveal
CT was 369 +/- 87 MUm. Choroidal thickness (CT) was 331 +/- 68 MUm for the
overall macula, 355 +/- 78 MUm for the 1-mm zone and 304 +/- 60 MUm for the 3-mm
zone. All CT measurements were thinner in myopic eyes (p < 0.0001) and in boys (p
< 0.05). We found no association between total PA and the CT by either mixed
model analysis (p = 0.074) or linear regression by any intensity levels (p =
0.22, p = 0.15 and p = 0.43). CONCLUSION: Among adolescents aged 14-17 years,
there was no association between objective PA exposures and the CT, AL or
refractive error.
PMID- 29338125
TI - Innovative case-writing software can engage millennials in learning pathology
topics.
PMID- 29338124
TI - Conservative therapy for chalazia: is it really effective?
AB - PURPOSE: To assess the within-treatment efficacy of hot compresses (HC), HC plus
tobramycin (Tobrex) and HC plus tobramycin/dexamethasone (Tobradex) for chalazia
treatment. METHODS: Design: Multicentre, randomized clinical trial
(ClinicalTrials.gov identifier, NCT01230593). SETTING: Two clinical sites in New
York and two clinical sites in Ontario. STUDY POPULATION: A total of 149 patients
with one or more chalazia on separate eyelids randomly assigned to receive HC (n
= 50), HC plus tobramycin (n = 50) or HC plus tobramycin/dexamethasone (n = 49).
INTERVENTION: 4-6 weeks of assigned treatment. Patients were measured for
chalazion horizontal width and surveyed for pain and treatment satisfaction
levels. MAIN OUTCOME MEASURES: Primary outcome was complete resolution (100% size
reduction). Secondary outcomes were size change in millimetres and patient
reported pre- and post-treatment pain and satisfaction levels. RESULTS: In the
intention-to-treat (ITT) population, complete resolution occurred in 36 (18%)
lesions total, 13 (21%) treated with HC, 12 (16%) with HC plus tobramycin and 11
(18%) with HC plus tobramycin/dexamethasone, with no significant difference
between them (p = .78). Individually by paired t-test, there were statistically
significant post-treatment mean size differences: HC 1.20 mm (p < 0.001), HC plus
tobramycin 1.69 mm (p < .001) and HC plus tobramycin/dexamethasone 1.54 mm (p <
0.001), but no significant difference between them (p = .61). Lesions that
completely resolved had a statistically significant lower pretreatment duration
(1.5 months) compared to lesions that did not completely resolve (2.2 months) (p
= .04). CONCLUSION: Hot compresses (HC) alone or in combination with tobramycin
or tobramycin/dexamethasone drops and ointment are all effective first-line
treatment options for chalazia. However, physicians may consider moving directly
to the use of more invasive therapies, such as incision and curettage or steroid
injections, for chalazia that have been present for more than 2 months, as older
lesions are less likely to resolve with conservative therapies alone.
PMID- 29338126
TI - Physical exercise and glaucoma: a review on the roles of physical exercise on
intraocular pressure control, ocular blood flow regulation, neuroprotection and
glaucoma-related mental health.
AB - The benefits of physical exercise on health and well-being have been studied in a
wide range of systemic and ocular diseases, including glaucoma, a progressive
optic neuropathy characterized by accelerated apoptosis of retinal ganglion cells
(RGCs). Elevated intraocular pressure (IOP) and insufficient ocular perfusion
have been postulated to be the two main theories in glaucoma development and
progression. The effects of exercise in these two aspects have been demonstrated
by numerous researches. A review in 2009 focusing on these two theories concluded
that exercise results in transient IOP reduction but an inconsistent elevation in
ocular perfusion. However, the majority of the studies had been conducted in
healthy subjects. Over the past decade, technological advancement has brought
forth new and more detailed evidence regarding the effects of exercise. Moreover,
the neuroprotective effect of exercise by upregulation of neurotrophin and
enhancement of mitochondrial function has been a focus of interest. Apart from
visual impairment, the mental health issues in patients with glaucoma, which
include anxiety and depression, should also be addressed. In this review, we
mainly focus on publications from the recent years, so as to provide a
comprehensive review on the impact of physical exercise on IOP, ocular perfusion,
neuroprotection and mental health in patients with glaucoma.
PMID- 29338127
TI - Establishment of practical recellularized liver graft for blood perfusion using
primary rat hepatocytes and liver sinusoidal endothelial cells.
AB - Tissue decellularization produces a three-dimensional scaffold that can be used
to fabricate functional liver grafts following recellularization. Inappropriate
cell distribution and clotting during blood perfusion hinder the practical use of
recellularized livers. Here we aimed to establish a seeding method for the
optimal distribution of parenchymal and endothelial cells, and to evaluate the
effect of liver sinusoidal endothelial cells (LSECs) in the decellularized liver.
Primary rat hepatocytes and LSECs were seeded into decellularized whole-liver
scaffolds via the biliary duct and portal vein, respectively. Biliary duct
seeding provided appropriate hepatocyte distribution into the parenchymal space,
and portal vein-seeded LSECs simultaneously lined the portal lumen, thereby
maintaining function and morphology. Hepatocytes co-seeded with LSECs retained
their function compared with those seeded alone. Platelet deposition was
significantly decreased and hepatocyte viability was maintained in the co-seeded
group after extracorporeal blood perfusion. In conclusion, our seeding method
provided optimal cell distribution into the parenchyma and vasculature according
to the three-dimensional structure of the decellularized liver. LSECs maintained
hepatic function, and supported hepatocyte viability under blood perfusion in the
engineered liver graft owing to their antithrombogenicity. This recellularization
procedure could help produce practical liver grafts with blood perfusion.
PMID- 29338128
TI - Clinical experience of laboratory follow-up with noninvasive prenatal testing
using cell-free DNA and positive microdeletion results in 349 cases.
AB - OBJECTIVE: Screening via noninvasive prenatal testing (NIPT) involving the
analysis of cell-free DNA (cfDNA) from plasma has become readily available to
screen for chromosomal and DNA aberrations through maternal blood. This report
reviews a laboratory's experience with follow-up of positive NIPT screens for
microdeletions. METHODS: Patients that were screened positive by NIPT for a
microdeletion involving 1p, 4p, 5p, 15q, or 22q who underwent diagnostic studies
by either chorionic villus sampling or amniocentesis were evaluated. RESULTS: The
overall positive predictive value for 349 patients was 9.2%. When a microdeletion
was confirmed, 39.3% of the cases had additional abnormal microarray findings.
Unrelated abnormal microarray findings were detected in 11.8% of the patients in
whom the screen positive microdeletion was not confirmed. Stretches of
homozygosity in the microdeletion were frequently associated with a false
positive cfDNA microdeletion result. CONCLUSIONS: Overall, this report reveals
that while cfDNA analysis will screen for microdeletions, the positive predictive
value is low; in our series it is 9.2%. Therefore, the patient should be
counseled accordingly. Confirmatory diagnostic microarray studies are imperative
because of the high percentage of false positives and the frequent additional
abnormalities not delineated by cfDNA analysis.
PMID- 29338129
TI - Three-dimensional visualization and volume quantification of pigment epithelium
detachments.
PMID- 29338130
TI - Correlation between morphological characteristics in spectral-domain-optical
coherence tomography, different functional tests and a patient's subjective
handicap in acute central serous chorioretinopathy.
AB - PURPOSE: The purpose of this study was to identify quantitatively measurable
morphologic optical coherence tomography (OCT) characteristics in patients with
an acute episode of central serous chorioretinopathy (CSC) and evaluate their
correlation to functional and psychological variables for their use in daily
clinical practice. METHODS: Retinal thickness (RT), the height, area and volume
of subretinal fluid (SRF)/pigment epithelium detachments were evaluated using the
standardized procedures of the Vienna Reading Center. These morphologic
characteristics were compared with functional variables [best-corrected visual
acuity (BCVA), contrast sensitivity (CS), retinal sensitivity/microperimetry,
fixation stability], and patients' subjective handicap from CSC using the
National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25).
RESULTS: Data from 39 CSC patients were included in this analysis. Three
different SRF height measures showed a high negative correlation (r = -0.7) to
retinal sensitivity within the central 9 degrees , which was also negatively
correlated with SRF area and volume (r = -0.6). The CS score and fixation
stability (fixation points within 2 degrees ) showed a moderate negative
correlation (r = -0.4) with SRF height variables. Comparison of the subjective
handicap with morphological characteristics in spectral-domain (SD)-OCT showed
SRF height had the highest correlation (r = -0.4) with the subjective problems
reported and overall NEI VFQ-25 score. CONCLUSION: In conclusion, SRF height
measured in SD-OCT showed the best correlation with functional variables and
patients' subjective handicap caused by the disease and therefore seems to be the
best variable to look at in daily clinical routine. Even though area and volume
also show a correlation, these cannot be so easily measured as height and are
therefore not suggested for daily clinical routine.
PMID- 29338131
TI - Gross anatomy education for South African undergraduate physiotherapy students.
AB - Eight faculties in South Africa offer undergraduate physiotherapy training with
gross anatomy included as a basis for clinical practice. Little information
exists about anatomy education for this student body. A 42-question peer-reviewed
survey was distributed to physiotherapy gross anatomy course coordinators in all
the eight faculties. Seven coordinators from six (75%) of the universities
responded. Two respondents' data from the same university were pooled. Collected
data show that staff qualifications and experience varied widely and high to
average staff to student ratios exist between faculties. Direct anatomy teaching
duration was 12.3 (SD +/-5.2) weeks per semester. Total number of weeks in
courses per faculty was 27.6 (SD +/-5.7) varying widely between institutions.
Calculable direct contact anatomy hours ranged between 100 and 308 with a mean of
207.6 (SD +/-78.1). Direct contact hours in lectures averaged 3.9 (SD +/-1.6) per
week and the average direct contact hours in practical sessions were 3.5 (SD +/
1.8) per week. Dissection, prosection, plastinated models, surface anatomy, and e
learning were available across faculties. Ancillary modalities such as vertical
integration and inter-professional learning were in use. All faculties had
multiple-choice questions, spot tests, and short examination questions. Half had
viva-voce examinations and one had additional long questions assessment. Students
evaluated teaching performance in five faculties. Four faculties were reviewing
anatomy programs to consider implementing changes to anatomy curriculum or
pedagogy. The findings highlighted disparity between programs and also identified
the need for specific guidelines to develop a unified South African gross anatomy
course for physiotherapy students.
PMID- 29338132
TI - Tumour thickness, diameter, area or volume? The prognostic significance of
conventional versus digital image analysis-based size estimation methods in uveal
melanoma.
AB - PURPOSE: The aim of this study was to compare conventional and novel size
estimation methods' ability to predict survival in uveal melanoma (UM). METHODS:
The study was designed as a retrospective consecutive chart review of patients
with UM, enucleated between the years 1984 and 1993. Area and volume were
estimated based on the largest histopathological cross-section, the second
centroid theorem of Pappus and digital image analysis, correlated to overall and
relative survival. RESULTS: Of 168 patients analysed, 20 (12%) of tumours were
categorized as T1, 47 (28%) as T2, 67 (40%) as T3 and 19 (11%) as T4 (15 N/a). A
total of 91 tumours with complete survival and measurement data were included and
recategorized into small, medium and large volume groups. Increased separation of
overall survival was seen compared with current American Joint Committee on
Cancer T categories. Difference between the large and small volume groups was 8.6
years (p = 0.001), compared to a difference of 5.6 years (p = 0.091) between T1
and T4. Hazard ratio for all-cause mortality in the large versus small volume
group was 2.6 compared to 1.9 for T4 versus T1. Relative survival rates for
small, medium and large volumes were 62, 44 and 31% at 10 years, versus 50, 45,
56 and 0% for T1, T2, T3 and T4. CONCLUSION: This study provides evidence that a
novel UM volume estimation method might offer a practical and cost-efficient
alternative to improve the prognostic value intrinsic to a tumour's size.
PMID- 29338133
TI - Pimasertib-associated ophthalmological adverse events.
AB - PURPOSE: To analyse ophthalmological adverse events associated with mitogen
activated protein kinase kinase (MEK) inhibition with pimasertib treatment for
metastatic cutaneous melanoma (CM). METHODS: In this prospective observational,
cohort-based, cross-sectional study, eight patients treated with the MEK
inhibitor pimasertib received a complete ophthalmic examination. This included
Early Treatment of Diabetic Retinopathy Study best-corrected visual acuity,
visual field testing, colour vision testing, slit-lamp examination, applanation
tonometry, indirect ophthalmoscopy, digital colour fundus photography and optical
coherence tomography (OCT). In selected cases, fluorescein angiography was
performed. RESULTS: Serous subretinal fluid (SRF) developed in all patients,
within a time frame of 9-27 days after the start of treatment. The fovea was
involved in six of eight patients (75%). None of the patients with foveal SRF
[excluding a patient who developed a bilateral retinal vein occlusion (RVO)]
experienced visual symptoms. Subretinal fluid (SRF) decreased or resolved in all
patients, despite continuation of study medication in six of eight patients
(75%). Complaints in the CM patient (13%) consisted of experiencing a dark fleck
in the inferior part of the visual field of the right eye 1 week after the start
of treatment, due to an RVO. Subsequent intravitreal bevacizumab treatment
resulted in functional and anatomical improvement. CONCLUSION: Patients with
metastatic CM who are treated with the MEK inhibitor pimasertib are at high risk
of development of ocular adverse events including serous retinopathy and possibly
RVO, stressing the need of adequate ophthalmological follow-up including OCT
during administration of pimasertib, despite the fact that SRF generally does not
lead to ophthalmological complaints.
PMID- 29338134
TI - Retinal oximetry is affected in multiple sclerosis.
AB - PURPOSE: Structural and physiological abnormalities have been reported in the
retina in patients with multiple sclerosis (MS). Retinal oximetry has recently
detected changes in retinal oxygen metabolism in Alzheimer's disease and mild
cognitive impairment. Our goal was to determine whether oxygen saturation in
retinal blood vessels of patients with patients is different from that of a
healthy population. METHODS: Oxygen saturation of haemoglobin was measured in
retinal blood vessels, using imaging with spectrophotometric noninvasive retinal
oximeter. Eight MS patients with history of optic neuritis were measured and
compared to 22 healthy individuals matched in age and gender. RESULTS: Venular
oxygen saturation was increased in patients with MS compared to healthy
individuals (70.7 +/- 3.4% versus 66.2 +/- 4.7; p = 0.021, mean +/- SD). The
arteriovenous (AV) difference was lower in patients with MS compared to healthy
(26.6 +/- 3.6% versus 30.5 +/- 4.8%; p = 0.049). There was no difference measured
in arterioles when patients with MS (97.3 +/- 1.7%) and healthy individuals (96.7
+/- 2.8%) were compared. CONCLUSION: Increased venular oxygen saturation and
lower AV difference in patients with MS may indicate reduced oxygen uptake. This
may be due to less oxygen demand following atrophy and may be a useful objective
biomarker for MS. Further studies are needed to confirm and expand these
findings.
PMID- 29338135
TI - The influence of type 2 diabetes mellitus on the frequency and complexity of
ventricular arrhythmias and heart rate variability in patients after myocardial
infarction.
AB - Background/Aim: After myocardial infarction arrhythmic cardiac deaths are
significantly more frequent compared to non-arrhythmic ones. The aim of the study
was to investigate the influence of type 2 diabetes mellitus (T2DM) on the
frequency and complexity of ventricular arrhythmias after myocardial infarction.
Methods: The study included 293 patients, mean age 59.5 +/- 9.21 years, who were
at least six months after acute myocardial infarction with the sinus rhythm,
without atrioventricular blocks and branch blocks. In the clinical group 95
(32.42%) patients were with T2DM, while 198 (67.57%) patients were without
diabetes. All of the patients were subjected to the following procedures:
standard ECG according to which the corrected QT dispersion (QTdc) was
calculated, exercise stress test, and 24-hour holter monitoring according to
which, the four parameters of time domain of heart rate variability (HRV) were
analyzed: standard deviation of all normal RR intervals during 24 hours (SDNN),
standard deviation of the averages of normal RR intervals in all five-minute
segments during 24 hours (SDANN), the square root of the mean of the sum of the
squares of differences between adjacent normal (RMS-SD), and percentage of
consequtive RR intervals which differed for more than 50 ms during 24 hours (NN >
50 ms). Results: In patients after myocardial infarction, patients with T2DM had
significantly higher percentage of frequent and complex ventricular arrhythmias
compared to the patients without diabetes (p < 0.001). The patients with T2DM had
significantly higher percentage of residual ischemia (p < 0.001), and arterial
hypertension (p < 0.001), compared to patients without diabetes. The patients
with T2DM had significantly lower values of HRV parameters: SDNN (p < 0.001);
SDANN (p < 0.001); RMS-SD (p < 0.001), and NN > 50 ms (p < 0.001), and
significantly higher values of QTdc (p < 0.001) compared to the patients without
diabetes. Conclusion: The study showed that type 2 diabetes mellitus has
significant influence on ventricular arrhythmias, HRV parameters and QT
dispersion in patients after myocardial infarction.
PMID- 29338137
TI - Morphological embryo selection: an elective single embryo transfer proposal.
AB - OBJECTIVE: To describe a patient selection method for elective single embryo
transfer (eSET), emphasizing inclusion criteria and results. METHODS: This
retrospective study included all cases seen in a private clinic between June 2011
and December 2016, in La Paz, Bolivia (3600 meters above sea level). Elective
single embryo transfer was the method of choice in 34 IVF/ICSI cycles, all in the
blastocyst stage. Gardner's blastocyst classification criteria were used. Between
the two stages of the study (July 2015), each embryo grade implantation rate was
recalculated, which led to the expansion of the inclusion criteria. RESULTS: The
clinical pregnancy rate of the 34 cases in the first transfer group was 55.9%
(19/34). Twin or multiple pregnancies did not occur. The cumulative pregnancy
rate to date is 64% [(19+3)/34]. The first stage comprised 2.56% (12/468) of the
patients offered elective single embryo transfers; the implantation rate was
58.3% (7/12). In the second stage, 14.29% (22/154) of the patients were eligible,
and the implantation rate was 54.55% (12/22). CONCLUSIONS: The implementation of
an eSET program based on in-depth morphological embryo assessment combined with
the calculation of the implantation potential of each embryo grade led to
acceptable clinical outcomes and fewer multiple pregnancies in patients
transferred two embryos. Each clinic should be aware of the implantation rates of
each embryo grade in its own setting.
PMID- 29338136
TI - Plasmatic estradiol concentration in the mid-luteal phase is a good prognostic
factor for clinical and ongoing pregnancies, during stimulated cycles of in vitro
fertilization.
AB - OBJECTIVE: To evaluate the predictive efficiency of serum estradiol (E2)
concentration in the mid-luteal phase regarding chemical, clinical, and ongoing
pregnancies, in patients subjected to IVF/ICSI with fresh embryo transfer.
METHODS: One hundred and forty-three patients undergoing IVF/ICSI met all the
inclusion criteria for the present study. Most of the patients used antagonists,
final maturation was achieved with recombinant chorionic gonadotrophin (HCG), and
embryo transfer took place on days 3 to 5, but mostly on day 4. The luteal phase
was supplemented with estradiol valerate 6 mg/day and vaginal micronized
progesterone 600 mg/day. There was no exclusion of patients in the embryo
transfer group due to age or ovarian reserve. All patients with estradiol and
chorionic gonadotrophin (betaHCG) dosage on the day of transfer, day 7, were
included. We assessed the following variables, initially regarding age: number of
eggs collected, formed embryos, embryos transferred, day of transfer, transfer
type, estradiol and chorionic gonadotropin. Next, we evaluated these elements at
three different ranges of estradiol concentrations (<200 pg/ml, 200-500 pg/ml,
and >500 pg/ml), comparing these parameters in pregnant (P) and non-pregnant (NP)
patients. RESULTS: Data analysis by age group in P and NP patients showed
significant differences in the mean values of the variables E2 and betaHCG, TD7.
Mean serum estradiol levels in P and NP in the three age groups were: <35 years,
835/417 p=0.0006, 35-39 years 833/434 p=0.0118, >39 years, 841/394 p=0.0012.
There was also a significant difference in pregnancy rates in the group >500
pg/ml of estradiol concentration (63.4%, p=0.0096). The likelihood of chemical
and clinical abortions for the estradiol ranges were: 38.46%, involving the two
first ranges versus 15.15% for a concentration >500 pg/ml, p=0.0412 and 5.26% for
a concentration >900 pg/ml, p=0.0105. The Pearson correlation coefficient for HCG
and estradiol was r=0.5108. CONCLUSION: This study showed the prognostic value of
E2 in the mid-luteal phase (TD7) for chemical, clinical, and ongoing pregnancies,
and its concentration suggested that there is a moderately positive correlation
with betaHCG levels.
PMID- 29338138
TI - Could cryopreserved human semen samples be stored at -80 degrees C?
AB - OBJECTIVE: To evaluate storage time effects in cryopreserved human semen samples,
kept in the freezer at a controlled temperature of -80 degrees C, on sperm
viability after thawing. METHODS: We used 20 semen samples. Each sample was
cryopreserved in 10 fingers, which were divided into five groups: one group was
kept in cryogenic canisters throughout the experiment(control), and four groups
were kept in a VIP Ultra Low MDF-U76V- PE freezer, with the temperature set at
80 degrees C, for 24, 48, 72 and 96 hours, respectively. After the exposure time,
the samples were stored in cryogenic canisters after being thawed. The analyzed
parameters were: motility, vitality and mitochondrial activity. RESULTS: After
thawing, we noticed decreased sperm motility, vitality and mitochondrial
activity, when comparing the tested groups with the control group, as well as a
progressive reduction in the analyzed parameters between the times evaluated.
CONCLUSIONS: Cryopreservation of semen samples at -80 degrees C is potentially
harmful to sperm viability, causing damage when submitted to longer exposure
times.
PMID- 29338139
TI - Occurrence of ovarian follicular dominance during stimulation for IVM impacts
usable blastocyst yield.
AB - OBJECTIVE: To evaluate the influence of ovarian follicular dominance on the
outcome of oocyte in-vitro maturation. METHODS: This retrospective cohort study
included 21 patients with polycystic ovaries or polycystic ovary syndrome
(Rotterdam criteria, 2004) subjected to 24 invitro maturation (IVM) cycles
between October 2015 and January 2017. Patients undergoing IVM received minimal
gonadotropin stimulation starting on day 2 or 3 of the cycle; ovum pick-up
typically occurred on days 6 to 8. No hCG-trigger shot was given. Following 30h
of IVM, mature oocytes were inseminated by ICSI and the resulting embryos
cultured up to the blastocyst stage. RESULTS: Ovarian follicular dominance was
observed in nine of the 24 IVM cycles. Oocyte IVM yielded an overall maturation
rate of 69.3+/-23.8%, and no difference was observed when the groups with or
without a dominant follicle were assessed independently. The rates of
fertilization and usable blastocysts per fertilized oocyte, mature oocyte
(Metaphase II) or cumulus-oocyte-complex were nearly three times higher (28.7+/
22.5%) in the group without ovarian follicular dominance. No differences were
found in the clinical pregnancy rates attained by the individuals with or without
a dominant follicle after 21 vitrified-warmed blastocyst transfer cycles.
CONCLUSION: Occurrence of ovarian follicular dominance during hormonal
stimulation for in-vitro maturation negatively impacted embryological outcomes.
Strategies devised to limit the appearance of ovarian follicular dominance must
be further explored.
PMID- 29338141
TI - Comparison of the efficacy of femoral nerve block and fascia iliaca compartment
block in patients with total knee replacement.
AB - BACKGROUND: Blocking the femoral nerve reduces postoperative pain and analgesic
consumption in patients who have undergone total knee and hip replacement
surgery. A limited number of studies have compared the efficacy of the fascia
iliaca compartment and femoral nerve block techniques. Therefore, this study
aimed to investigate the analgesic effectiveness of fascia iliaca compartment
block (FIB) and femoral nerve block using ultrasound. METHODS: A total of 100
patients were included in the study. Patients were divided into two randomized
and equal groups (Group I had patients who underwent fascia iliaca compartment
block, N.=50; Group II had patients who underwent femoral nerve block, N.=50).
Visual Analogue Scale levels (VAS) in the postoperative 30th min and 1st, 2nd,
6th, 12th and 24th hours and the amounts of analgesic consumption were recorded.
The Quality of Recovery-40 (QoR-40) questionnaire was completed by patients 24
hours after surgery. RESULTS: The VAS level at the 24th hour was significantly
lower in Group I compared to Group II. Analgesic consumption between 0-30th
minutes was lower in Group II than in Group I; however, it was significantly
lower in the 6-24 hours of Group I compared to Group II. The QoR-40 score was
found to be significantly higher in Group I than Group II. CONCLUSIONS: Femoral
nerve block provided more potent analgesia in the first six hours after
operation. After six hours, FIB demonstrated better pain control. The quality of
postoperative recovery was higher in patients with fascia iliaca compartment
block.
PMID- 29338140
TI - Primary pyomyositis in North India: a clinical, microbiological, and outcome
study.
AB - BACKGROUND/AIMS: Pyomyositis is an infective condition with primary involvement
of the skeletal muscles. There is sparse recent literature on patients with
pyomyositis. METHODS: This study was carried out at emergency services of a
tertiary care center located in subtropical area of Indian subcontinent. RESULTS:
Sixty-two patients of primary pyomyositis formed the study cohort. Mean age of
occurrence was 29.9 +/- 14.8 years. There were 54 men. Twelve patients had
underlying medical diseases. Muscle pain was seen in all 62 patients. Forty-eight
patients (77.4%) had the fever. Most common site of involvement was thigh muscles
(n = 29, 46.8%). Forty-nine patients (79%) presented in the suppurative stage of
illness. Patients with comorbidities were older (age: median 36 years
[interquartile range (IQR), 25 to 47] vs. 24 years [IQR, 16 to 35], p = 0.024),
had higher culture positivity with gram-negative organisms (8/9 [88.89%] vs. 6/29
[20.69%], p = 0.001). Importantly, higher number of these patients received
inappropriate antibiotics initially. Patients with positive pus culture result
had higher complication rate (32/38 [84.21%] vs. 10/18 [55.56%], p = 0.044). Six
patients (9.7%) had in-hospital mortality. Lower first-day serum albumin, initial
inappropriate antibiotic therapy, and advanced form of the disease at
presentation were associated with increased in-hospital mortality. CONCLUSIONS:
Primary pyomyositis is not an uncommon disease entity. Patients with
comorbidities were more likely to receive initial inappropriate antibiotic
therapy. Patients with positive pus culture report had the higher rate of
complications. Lower first-day serum albumin, initial inappropriate antibiotic
therapy and advanced form of the disease at presentation were associated with
increased in-hospital mortality.
PMID- 29338142
TI - Patient-controlled epidural analgesia with and without basal infusion using
ropivacaine 0.15% and fentanyl 2gamma/mL for labor analgesia: a prospective
comparative randomized trial.
AB - BACKGROUND: Patient-controlled epidural analgesia (PCEA) is a common practice for
labor pain relief. This study aimed to compare two different settings of a PCEA
device using the same solution to obtain labor analgesia. METHODS: Fifty-two
parturients were randomly allocated to receive ropivacaine 0.15% and fentanyl 2
gamma/mL via a PCEA device either as a background infusion of 5 mL/h plus 5 mL
demand bolus doses with 10-minute lockout (group B/D, N.=26) or as only demand
bolus doses of 5 mL with 10-minute lockout (group D, N.=26). The primary outcome
was the total volume of local anesthetic administrated during labor; secondary
outcomes included the analgesic efficacy and the effects on maternal and neonatal
outcomes. RESULTS: No statistical difference was observed between the groups
concerning demographic characteristics, duration of first and second stages of
labor, administration of oxytocin and ephedrine, rescue doses, instrumental
delivery, Bromage Scale, maternal side effects and satisfaction, neonatal Apgar
scores and pH. The total volume of local anesthetic was greater in group B/D
compared to group D (P=0.015). A statistically significant difference was
detected in VAS scores only at the end of the second stage (P=0.036) and at 60
minutes from the test dose administration (P=0.022) and with group D exhibited
higher pain scores than group B/D. The incidence of breakthrough pain (VAS>4) was
higher in group D compared with group B/D (P=0.035). CONCLUSIONS: The addition of
background infusion plus PCEA demand bolus doses increased local anesthetic
consumption and reduced breakthrough pain without affecting maternal satisfaction
and neonatal outcomes.
PMID- 29338143
TI - Anesthesiology Resident Induction Month: a pilot study showing an effective and
safe way to train novice residents through simulation.
AB - BACKGROUND: The transition of new residents from medical school to the post
graduate clinical environment remains challenging. We hypothesized that an
introductory simulation course could improve new residents' performance in
anesthesiology. METHODS: The Anesthesiology Residents Induction Month (ARIM)
program was designed as a non-clinical simulation training program aiming at
providing the theoretical and practical skills to safely approach, as junior
anesthesiologists, the operating rooms. For each participant, specific knowledge,
procedural skills and non-technical performance were assessed with a pre and post
test approach, before and immediately after the participation in the study.
RESULTS: Fifteen first-month residents participated in the study. As compared to
pre-test, residents significantly improved in all three evaluated areas. Pre-test
knowledge assessment mean improved from 56% to 73% in the post-test (P<0.001). In
the procedural skills assessment, pre-test mean improved from 43% to 77%
(P<0.001) and non-technical skills assessment improved from 3.17 to 4.61 (in a
scale out of seven points) in the post-test (P<0.001). CONCLUSIONS: Data suggest
that an intensive simulation-based program can be an effective way for first-year
residents to rapidly acquire and develop basic skills specific to anesthesiology.
There might be benefits to begin residency with a training program aiming at
developing and standardizing technical and non-technical skills.
PMID- 29338144
TI - Mortality and long-term quality of life after percutaneous tracheotomy in
Intensive Care Unit: a prospective observational study.
AB - BACKGROUND: Quality of life and mortality after percutaneous dilatational
tracheotomy (PDT) has been poorly investigated. The aims of this study were to
evaluate the independent risk factors for Intensive Care Unit (ICU) mortality and
investigate quality of life over the first year after PDT in critically ill
patients. METHODS: This was a prospective, single-center, cohort study performed
in a tertiary care University Hospital, enrolling consecutive ICU patients
requiring elective PDT, collecting data during the tracheotomy procedure and the
ICU stay. Follow-up was performed at three, six and twelve months after PDT. The
medical interview included the Euro Quality of Life questionnaire comprising five
dimensions (mobility, self-care, usual activities, pain/discomfort,
anxiety/depression). RESULTS: A total of 137 patients were included in the study.
In the multivariate analysis, ICU mortality was independently associated with age
(OR 1.089; P=0.003) and SAPS II (OR 1.047; P=0.003), and inversely with
neurologic disease (OR 0.162; P=0.004). Mortality increased over time (ICU
mortality 26.7%; in-hospital mortality 43.1%; 3-months mortality 47.4%; 6-months
mortality 61.3%; and 1-year mortality 70.8%; P=0.0001). Tracheostomized patients
due to respiratory disease had a higher ICU mortality (50%) compared to those
with neurological disease (13.6%). quality of life (QoL) of tracheostomized
patients was severely compromised at 3-months (QoL: 17, 15-19), 6-months (QoL:
17; 16-19), while moderately compromised at 1-year (QoL: 13; 9-16). A subgroup
analysis showed better QoL at 3-months, 6-months and 1-year in respiratory
compared to neurological tracheostomized patients (P=0.01). CONCLUSIONS: Patients
baseline characteristics and indication for PDT procedure are important
determinants of in-ICU mortality and QoL in tracheostomized patients.
PMID- 29338145
TI - Association between Bispectral Index System and airway obstruction: an
observational prospective cohort analysis during third molar extractions.
AB - BACKGROUND: Sedation regimes during oral procedures frequently associated with
airway obstruction. The aim of this study was to define the association of
Bispectral Index (BIS) to the depth of sedation and airway obstruction events.
METHODS: Forty-seven patients between 14-21 years old, who were candidates for
3rd molar teeth extraction, were enrolled in this study. Patients received a
total of 4 mg midazolam, 100 microgram fentanyl followed by titrated incremental
propofol in 10 mg. The Richmond Agitation Sedation Score (RASS) was used to
assess the depth of sedation. Each patient was attached to BIS monitor, while
clinicians were not involved in the data collection process. Apnea, airway
obstruction, O2 saturation, timing and interventions for controlling the
situation were recorded. All data was synchronized with BIS data monitoring.
RESULTS: The results show that 97.5% of cases were ASA 1 and 2, with average age
of 17.3 years (+/-1.4) and a median BMI of 26.1. By using linear regression, for
every unit decrease of median RASS (less than zero), there was 1.78 decrease in
mean BIS Score (P=0.045, 95% CI: 0.08-3.47). The mean BIS Index (over 1 minute)
with airway obstruction was 64 (+/-10.2), which was significantly lower than the
BIS during non-airway obstruction (77+/-11.6), (P<0.001). By using logistic
regression analysis, for every on unit increase in BIS Index, there is 24%
decrease in odds in having airway obstruction (P=0.0009, 95% CI: 0.65-8.94).
CONCLUSIONS: This study demonstrates that the BIS could potentially be a valid
continuous monitoring method to avoid airway obstruction during sedation for
patients undergoing dental surgery.
PMID- 29338146
TI - The effect of various doses of infusion solutions on the endothelial glycocalyx
layer in laparoscopic cholecystectomy patients.
AB - BACKGROUND: The endothelial glycocalyx is located on the luminal side of blood
vessels and maintains vessel integrity. This study analysed how various dosages
of infusion affected the secretion of atrial natriuretic peptide (ANP) and
potential glycocalyx damage in patients undergoing laparoscopic cholecystectomy.
We hypothesised that the liberal administration of Ringer's solution during the
operation can cause iatrogenic hypervolemia with releasing of ANP and glycocalyx
damage. METHODS: The study included 90 patients with American Society of
Anesthesiologists' (ASA) class I and II, in good cardiopulmonary health, who were
assigned to one of three groups: Restrictive group, which received 1 mL/kg/hr
intraoperatively and six hours postoperatively; Low liberal group, which received
5 mL/kg/hr of Ringer's solution intraoperatively and six hours postoperatively
and High liberal group, which received 15 mL/kg/hr intraoperatively and 10
mL/kg/hr six hours postoperatively. We measured patients' concentrations of
glycocalyx constituents, ANP, markers of kidney and liver function, C-reactive
protein (CRP), and albumine at three time points. We also measured noinvasive
hemodynamics, the correlation between ANP secretion and the concentration of
glycocalyx components. RESULTS: We found a significantly higher concentrations of
hyaluronic acid and syndecan-1 and more ANP secretion in the High liberal group
than in the other groups. We also observed a positive correlation between ANP
secretion and glycocalyx constituent concentration. Markers of kidney and liver
function were normal, suggesting preservation of splanchnic perfusion and global
hemodynamics. CONCLUSIONS: Measuring the endothelial glycocalyx constituents in
circulating blood could be a marker of intraoperative volume overload during
laparoscopic operations.
PMID- 29338147
TI - Effect of therapeutic hypothermia on survival and neurological outcome in adults
suffering cardiac arrest: a systematic review and meta-analysis.
AB - INTRODUCTION: The aim of this review was to determine current evidence for the
effect of therapeutic hypothermia (TH) on survival and neurological outcome in
adults suffering cardiac arrest (CA). EVIDENCE AQUISITION: We searched the
Cochrane Controlled Trials Register, MEDLINE, EMBASE and NLM databases from 2000
to 2017 using the following terms: hypothermia, cooling, therapeutic, cardiac
arrest, resuscitation, cardiopulmonary, CPR. Studies were eligible if they
compared TH versus normothermic management in adult humans sustaining CA.
Randomized controlled trials (RCT), pilot studies and observational trials were
included. EVIDENCE SYNTHESIS: Ten studies involving 3259 patients were included
in meta-analysis. Pooling all eligible studies showed a favorable effect for TH
on survival and neurological recovery. However, sensitivity analysis for RCTs
showed no benefit on either outcome, while observational trials showed benefit
for neurological recovery with just marginally significant benefit regarding
survival. Studies including patients with shockable rhythms demonstrated benefit
for both outcome measures, while those including patients with any rhythms
demonstrated benefit for neurological recovery but not for survival. TH did not
benefit patients with non-shockable rhythms. Trials using external cooling
favored TH regarding survival and neurological outcome but those using systemic
cooling with or without external cooling did not show such benefit. When the
overall incidence of complications was pooled, there was a statistically
significant shift in odds ratio favoring normothermic management over TH.
CONCLUSIONS: Evidence from RCTs suggests TH does not improve survival or
neurological outcome, while observational trials favor TH over normothermia. TH
may be attended with higher risk for complications.
PMID- 29338148
TI - Novel applications of bedside monitoring to plumb patient hemodynamic state and
response to therapy.
AB - Hemodynamic monitoring is essential during the treatment of the critically ill in
order to address the hemodynamic alterations and assess the response to
treatment. Traditionally classified causes of shock and underlying
pathophysiological mechanisms are often neglected by resuscitative strategies
included in the guidelines. Most of hemodynamic management focuses on the ability
to early recognize patients susceptible to increase cardiac output (CO) and mean
arterial pressure (MAP) after a defined fluid challenge by eliciting Starling's
law of the heart, and less is known of the ones presenting in shock and not
volume responsive. All this influences the application of hemodynamic monitoring
tools and their interpretation. Functional hemodynamic monitoring strategies,
aiming to overcome limitations of traditional static pressures measurements, have
been developed and recently acknowledged by guidelines for the treatment of
septic shock. Nevertheless, those techniques share the same limitations of
previous ones, being poorly reliable in various common situations such as in
spontaneous breathing patients, right ventricular dysfunction of several causes
or if arrhythmia occurs. Echocardiography has now become commonplace in the
evaluation of the hemodynamic profile in the critically ill and mastering this
technique is important in order to interpret pathophysiological patterns behind
hemodynamic alteration while at the same time, screening for unexpected findings.
More recently, pathophysiological and echocardiographic-based approaches have
been introduced to investigate ventriculo-arterial coupling, the relationship
between both left and right heart and the relative circulatory bed. Such
techniques allowed establishing that in many critically ill scenarios, coupling
between the heart and the circulation is inefficient and probably that is the
reason why in this case hemodynamic restoration cannot be achieved by standard
approaches. Combining echocardiography to better understand and treat in real
time pathophysiological determinants of altered hemodynamic states with
functional approaches seems to be the key to plumb hemodynamic states although it
remains to be demonstrated if this tailored approach will improve patient
outcome.
PMID- 29338149
TI - Injection pressure mapping of intraneural vs. perineural injections: further
lessons from cadaveric studies.
AB - BACKGROUND: The aim of the study was to investigate the difference between
intraneural and perineural injection pressures in human cadavers. Targeted nerves
included the cervical roots, the supraclavicular and infraclavicular brachial
plexus, the sciatic-subgluteal nerve and the common peroneal and tibial nerves.
METHODS: Ten readings were obtained for each nerve location. Over ten seconds, 1
mL of 0.9% NaCl was injected - deliberately slower than in clinical practice to
eliminate the risk of aberrant readings relating to the speed of injection.
Perineural injections occurred at least 1 mm outside the epineurium. After
pressure recordings were completed 0.1mL of dye was injected, and dissection
performed to confirm needle placement. Ultrasound and dissection images were
matched with light microscopy pictures for all locations. RESULTS: The average
pressure for intraneural injections was 24.1+/-5.7 psi and 6.1+/-2.1 psi for
perinereural. The average injection pressure generated for the cervical trunk,
supraclavicular, infraclavicular, sciatic subgluteal, peroneal and tibial nerves
respectively were 31.2+/-6.0 psi, 24+/-15.0 psi, 23.4+/-9.5 psi, 22.6+/-8.8 psi
19.7+/-6 psi, 17+/-7.3 psi intraneurally and 6.1+/-2.0 psi, 9.1+/-5.5 psi, 10+/
4.9 psi, 6+/-2.4 psi, 6+/-2.4 psi and 7+/-2.5 psi perineurally. For intraneural
injections statistically significant differences were demonstrated between the
peroneal and tibial nerves compared to cervical roots/trunks/division/cords of
brachial plexus. CONCLUSIONS: The study has consistently demonstrated
statistically significant differences between intraneural and perineural
injection pressures. It effectively created a "map" of intraneural injection
pressures for the most common peripheral nerves blocks and demonstrated a pattern
between proximal and distal locations. The study also revealed limitations of
either techniques, ultrasound and injection pressure monitoring reinforcing the
concept of their simultaneous application.
PMID- 29338150
TI - The role of cannabinoids in pain control: the good, the bad, and the ugly.
AB - Cannabinoids appear to possess many potential medical uses, which may extend to
pain control. A narrative review of the literature has found a variety of studies
testing botanical and synthetic cannabinoids in different pain syndromes (acute
pain, cancer pain, chronic noncancer pain, fibromyalgia pain, migraine,
neuropathic pain, visceral pain, and others). Results from these studies are
mixed; cannabinoids appear to be most effective in controlling neuropathic pain,
allodynia, medication-rebound headache, and chronic noncancer pain, but do not
seem to offer any advantage over nonopioid analgesics for acute pain.
Cannabinoids seem to work no better than placebo for visceral pain and conferred
only modest analgesic effect in cancer pain. Cannabinoids do many good things -
they appear to be effective in treating certain types of pain without the issues
of tolerance associated with opioids. Negatively, marijuana currently has a very
murky legal status all over the world - laws regulating its use are inconsistent
and in flux. Thus, both patients and prescribers may be unsure about whether or
not it is an appropriate form of pain control. Cannabinoid-based analgesia has
been linked to potential memory deficits and cognitive impairment. A great deal
more remains to be elucidated about cannabinoids which may emerge to play an
important role in the treatment of neuropathic and possibly other painful
conditions. There remains a great deal more to learn about the role of
cannabinoids in pain management.
PMID- 29338151
TI - Oral prolonged-release oxycodone/naloxone offers equivalent analgesia to
intravenous morphine patient-controlled analgesia after total knee replacement. A
randomized controlled trial.
AB - BACKGROUND: The purpose of this study was to determine whether oral prolonged
release oxycodone-naloxone combination (OXN) could provide equivalent analgesia
and a side-effect profile similar to intravenous morphine patient-controlled
analgesia (IVPCA) for the control of pain in the immediate postoperative period
after total knee replacement (TKR). METHODS: All patients received a sciatic
nerve block with 0.3% ropivacaine 15 mL, femoral nerve block with 0.5%
ropivacaine 20 mL, spinal anesthesia and postoperative continuous femoral nerve
infusion (ropivacaine 0.2% 4 mL/h). After surgery, patients were randomly
allocated to receive either 10 +10 +5 mg controlled release OXN oral
administration 12 hourly or IVPCA with morphine (2 mg bolus, no basal infusion).
The primary outcome was the average rest and dynamic pain for the first 48 h
postoperatively. Secondary outcomes were: post operative nausea vomiting (PONV)
and the total morphine consumption. RESULTS: OXN group experienced better pain
control at rest during the first (0.89+/-1.54 vs. 1.27+/-1.82, P=0.0019) and
second (1.03+/-1.69 vs. 1.65+/-2.05, P=0.0006) postoperative period. There was no
statistically significant difference in pain score during movement between the
two groups. The secondary outcome measures showed no significant differences in
the total morphine consumption (12.04+/-1.1 vs. 11.46+/-3.7 mg, P=0.20) or PONV
(0.6+/-0.8 vs. 0.8+/-1.0, P=0.40). CONCLUSIONS: This study show that in the
immediate postoperative period after TKR, the patients receiving oral prolonged
release OXN experienced the same to better pain control than those receiving
morphine IVPCA, with a similar degree of PONV.
PMID- 29338152
TI - Generation and Characterization of Siglec-F-Specific Monoclonal Antibodies.
AB - Siglec-F (SF) is a surface glycoprotein expressed by mouse eosinophils and
induces caspase- and mitochondria-dependent apoptosis after engagement with its
cognate ligand or specific antibodies. This targeting eosinophils by monoclonal
antibodies may help diverse diseases associated with increased frequency of
eosinophils including allergy and asthma. In this paper, production of murine and
rat monoclonal antibodies (mAbs) against Siglec-F has been addressed. Balb/c mice
were immunized with siglec-F1 (SF1) and siglec-F2 (SF2) synthetic peptides
conjugated to a carrier protein. Rats were immunized with Chinese hamster ovary
CHO cells overexpressing Siglec-F (CHO-SF) or with Siglec-F-human immunoglobulin
FC fusion protein (CHO-SF-Ig). Hybridomas were produced by standard protocol and
screened for their reactivity by enzyme-linked immunosorbent assay (ELISA),
western blotting (WB), and flow cytometry. In parallel, polyclonal antibodies
were generated in New Zealand White rabbits immunized with SF1 and SF2 peptides.
Three mouse and three rat mAbs were generated against synthetic peptides and SF
Ig, respectively. All mouse monoclonal and rabbit polyclonal antibodies reacted
well with immunizing molecules in ELISA and detected specific band of Siglec-F in
WB. However, they failed to detect native molecule in flow cytometry analysis.
Quite the contrary, rat mAbs did not reacted with the denatured protein in WB,
instead exhibited significant reactivity with CHO-SF cells in flow cytometry.
Based on the heavily glycosylated nature of Siglec-F, it seems that generation of
anti-SF antibodies able to detect native protein needs a properly folded molecule
for immunization. Monoclonal antibodies reported here are invaluable tools for
studying linear and conformation epitopes of SF and tracing mouse eosinophils.
PMID- 29338153
TI - Association Study of CD226 and CD247 Genes Single Nucleotide Polymorphisms in
Iranian Patients with Systemic Sclerosis.
AB - CD247 and CD226 play important roles in signaling of lymphocytes. Single
nucleotide polymorphisms (SNPs) of genes encoding CD247 and CD226 have been
associated with the risk of several autoimmune disorders. This study aimed to
evaluate the possible association between CD226 and CD247 genes SNPs and risk of
systemic sclerosis (SSc) in Iranian population. Study participants were 455 SSc
patients and 455 age, sex and ethnic -matched healthy individuals. Genotyping of
rs2056626 and rs763361 at CD247 and CD226 genes, respectively, was carried out
using TaqMan MGB-based allelic discrimination real-time PCR. Neither alleles nor
genotypes of both SNPs showed significant association with the risk of SSc.
Furthermore, association analysis of the genotypes with clinical manifestations
of the disease revealed that rs763361 variants were associated with the forced
vital capacity (FVC) in SSc patients. Our results suggest that genetic variants
of CD226 and CD247 genes may not be a contributing factor in pathogenesis of SSc
in Iranian population.
PMID- 29338154
TI - Characteristics, Etiology and Treatment of Pediatric and Adult Anaphylaxis in
Iran.
AB - Despite the increasing prevalence of anaphylaxis, there is little information
about the characteristics and practice of healthcare providers in treating
anaphylaxis, so this study was conducted to record the characteristics and
therapeutic approaches of anaphylaxis from May 2012 until April 2015, the data of
all patients diagnosed with anaphylaxis in the Allergy department of three
referral university hospitals in Tehran, Iran were recorded. Thereafter, the
demographics, clinical features, triggers and therapeutic approach were
evaluated. This study investigated 136 individuals, 64 males (47%) between 6
months and 68 years old, as well as 72 others (52.94%) under 18 years of age
(pediatric). The following were the most common organs involved: Skin 86.02%
(pediatric 91.66% vs adult 79.68%), respiratory tract 51.47% (pediatric 43.05% vs
adult 60.93%), cardiovascular 50.73% (pediatric 54.16% vs adult 46.87%),
gastrointestinal 20.58% (pediatric 27.7% vs adult 12.5% ) and neurologic system
5.88% (only in adults). The following were the most identified causing foods 69
(50.37%)[42 pediatric (children) and 27 adults], drugs 34( 25%)[14 pediatric and
20 adults], idiopathic 16( 11.77%)[3 pediatric and 13 adults], insect sting 7(
5.15%)[3 pediatric and 4 adults] , exercise 6( 4.42%) [1 pediatric and 5 adults].
Milk, egg and wheat were the most common causative foods in pediatric cases but
sesame, as well as egg and milk were the most common causes in adults.
Epinephrine injection, auto injector epinephrine prescription as a discharging
plan and referral to an allergist were: 10.78, 1.96 and 7.8 %, respectively. In
this case series we found that, cutaneous, respiratory, cardiovascular and
gastrointestinal complains were the most common manifestations and food, drug and
idiopathic were the most common causes.In this study, the diagnosis of
anaphylaxis, epinephrine subscription and referral to an allergist were
significantly lower in comparison to other studies.
PMID- 29338155
TI - Association between Caregiver Exposure to Toxics during Pregnancy and Childhood
onset Asthma: A Case-control Study.
AB - The aim of this study was to evaluate the associations between caregiver-reported
use of medications, alcohol, cigarette and/or waterpipe (WP), and exposure to
pesticides/detergents during pregnancy with childhood-onset asthma. The study
design consisted of a case-control study, conducted between December 2015 and
April 2016, recruited 1503 children, aged between 3-16 years old. A questionnaire
assessed the sociodemographic characteristics (age, gender, education level of
both parents), the family history of asthma, and other known risk factors of
asthma (heating system at home, child history of recurrent otitis, humidity in
the house, child went to a daycare, smoking and drinking alcohol during
pregnancy, exposure to pesticides and detergents). The multivariate analysis
showed that children living in North and South Lebanon and the children living in
areas where pesticides are frequently used had an increased risk of asthma
(ORa=1.625, CI 1.034-2.554, p=0.035, ORa=13.65, CI 3.698-50.385; p<0.001 and
ORa=3.307, CI 1.848-5.918, p<0.001 respectively). Smoking WP during pregnancy and
cigarette during lactation would increase the risk of asthma in children
(ORa=6.11; CI 1.244-30.008; p=0.026 and ORa=3.44; CI 1.024-11.554; p=0.046
respectively). We conclude that asthma may originate from the environmental
exposure to toxics such as pesticides and tobacco (cigarettes and WP) or to
alcohol and prescribed medications during pregnancy and lactation. Spreading
awareness by health professionals about these preventable causes can help educate
the parents and children to prevent asthma and its exacerbation.
PMID- 29338156
TI - Attenuating Effect of Long-term Culture of Umbilical Cord Vein Mesenchymal
Stromal Cells on Pulmonary Fibrosis in C57BL/6 Mice.
AB - In recent studies, mesenchymal stromal cells (MSCs) have been increasingly
employed to treat various diseases like pulmonary fibrosis (PF). There are very
few MSCs in tissues so in order to obtain their sufficient numbers for
therapeutic applications, their in vitro expansion is necessary. The aim of this
study was to investigate the effects of long-term culture of the human umbilical
cord vein MSCs (hUCV-MSCs) on pulmonary fibrosis in mice. MSCs were first
isolated from human umbilical cord vein and cultured up to 18 passages. In
C57BL/6 mice, 15 min after belomycin instillation, UCV-MSCs at passages (P) 0, 4,
8, 12, and 18 (long-term culture) were transplanted intratracheally. Mice were
weighted every 5 days and were euthanized on day 21. For histopathological
examination, the lung sections were stained with hematoxylin-eosin (HE) and
Masson's trichrome. The mRNA expression of TGF-beta1, alpha-smooth muscle actin
(alpha-SMA), and collagen type I alpha 1 (COL1A1) in lung tissues were assessed
using RT-PCR. For cell tracking, human cytochrome B DNA was detected in mice lung
tissues by PCR. The weight of mice receiving long-term culture of UCV-MSCs
increased compared to other mice (p=0.056). Also, transplantation of UCV-MSCs at
P18 led to increased alveolar space and decreased connective tissue and collagen
deposition of the lung tissues. The mRNA expression of TGF-beta1, alpha-SMA, and
COL1A1 also decreased in this group. The results showed that intratracheally
transplanted long-term culture of the UCV-MSCs attenuated lung fibrosis in mice.
PMID- 29338157
TI - Imbalance of Th17/Treg in the Pathogenesis of Mice with Paraquat-induced Acute
Lung Injury.
AB - Recent studies suggest that imbalances in the ratios of CD4+ T helper cell
subsets, T helper-17 (Th17) and regulatory T (Treg) cells play a crucial role in
the pathogenesis of acute lung injury (ALI). However, studies of the imbalance of
Th17/Treg in paraquat (PQ)-induced ALI have not been reported. Therefore, we
investigated whether the ratio of Th17/Treg cells in a mouse model of PQ-induced
ALI contributes to pathogenesis of ALI. Male Kunming mice were randomly treated
with saline (control group) or PQ (PQ-poisoned (PQP) group); mice were sacrificed
at either 12 hours (PQP-12h) or 24 hours (PQP-24h and control) post-treatment.
Hematoxylin-eosin and TUNEL staining procedures were performed to examine
inflammation and apoptosis. The presence of Th17 and Treg cells was measured by
flow cytometry; the expression of putative Th17 cytokines and transcription
factors was measured by ELISA and western blot analysis. Compared with control
mice, lung inflammation and apoptosis were dramatically increased in PQP mice at
12 and 24 hours after poisoning. In addition, poisoned mice displayed significant
increases in the presence of CD4+IL-17+ T cells (Th17) and in the expression of
IL-17A and IL-17, as measured by flow cytometry and western blot assays. This
increase was most notable after 24 hours of PQ exposure. Furthermore, poisoned
mice displayed marked decreases in the presence of CD4+CD25+Foxp3+ T cells (Treg)
and in the expression of IL-35 and the transcription factor Foxp3. These results
suggest that an imbalanced ratio of Th17/Treg cells may contribute to the
pathogenesis of PQ-induced ALI.
PMID- 29338158
TI - Studying the Serum as Well as Serous Level of IL-17 and IL-23 in Patients with
Serous Otitis Media.
AB - Serous otitis media with effusion (OME) is a middle ear inflammatory response to
allergens and microbes which stimulate leukocytes to produce different
inflammatory mediators after obstruction of Eustachian tube. Here, we
investigated the levels of these mediators, IL-17 and IL-23, in serum and middle
ear fluids of children with OME. 75 patients with otitis media and 75 age and sex
matched healthy controls were enrolled in this study. IL-17 and IL-23 levels in
serous secretion of the patients and their serum levels were measured in both
groups by ELISA. Serum IL-17 levels were significantly higher in the patients
than controls (p=0.001). There was no significant difference between serum IL-23
levels in patients and controls. Patients' serous levels of both cytokines of IL
17 and IL-23 were higher than those in serum according to different parameters of
sex, age, and duration of the disease. This study shows an elevated presence of
IL-17 and IL-23, as pro inflammatory cytokines, in OME. These finding may
represent the contribution of such cytokines in the pathogenesis of OME. Blocking
such molecules may yield new non-surgical therapeutics.
PMID- 29338159
TI - Ovariectomy Modifies TH2, and TH17 Balance in BALB/C Allergic Mice.
AB - Asthma is a chronic inflammation of the airways affecting over 300 million people
worldwide. As in the autoimmune diseases, it is well described that women are the
most affected by asthma. The higher number of women presenting this pathology
suggests the involvement of female sex hormones in the construction of the
allergic immune response. Female Balb / c mice were used for the experiments.
Thirty-eight animals were separated into four groups: OVX-Ova; Sham-Ova; OVX-Sal;
Sham-Sal. Then animals underwent acute allergic induction protocol by Ovalbulmin
(OVA). Ovariectomized animals showed greater number of leukocytes in
bronchoalveolar lavage (BAL) and elevated white blood cells recruitment to the
lung environment observed by histological analysis. There was a significant
increase of eosinophils and mast cells in inflammatory sites at pulmonary tissue.
The relative uterine and body weight were lower in ovariectomized animals and
higher in Sham mice, respectively. Moreover, the lack of the sex hormones induced
an increase in interleukin (IL)-4 and titers of immunoglobulin G1 (IgG1)
antibodies. However, increased production of IL-17A was only observed in Sham
animals. Altogether, data this study suggest that ovariectomy induces the
formation of a stronger Th2 response in allergic animal. However, the immune
processes involved in the allergic response in females currently remain unclear.
PMID- 29338160
TI - Higher Activities of Hepatic Versus Splenic CD8+ T Cells in Responses to Adoptive
T Cell Therapy and Vaccination of B6 Mice with MHC Class-1 Binding Antigen.
AB - The liver has unique microenvironment which is known to induce tolerance of
cytolytic CD8+ T cells to hepatic and extra hepatic antigens, resulting in
persistence of infection of the liver by the hepatitis B and C viruses. However,
under some conditions, functional immune responses can be elicited in the liver
in particular to show preferential retention of activated CD8+ T cells. It is not
clear whether this retention depends on the type of the exogenous
immunostimulatory or the endogenous innate immune cells. The T cell receptor
(TCR) transgenic OT-1 (CD8+) mouse model was used in which OT-1 cells were
harvested from the spleen of the donor and transferred into recipient mice
followed by immunization with OVA peptide followed by injection of GM-CSF, CCL21
chemokine, or cytokines (IL-2, IL-12, or IL-15), or the toll-like receptor 3
agonist poly(I:C). Co-administration of any of these immunostimulatory agents
relatively augmented the retention of CD8+ T cells with different levels of
effects. Compared to spleen, the Ag-specific CD8+ T cells in the liver showed
higher activities including expansion, proliferation, apoptosis and memory
responses as well as cytolytic function. While depletion of natural killer cells
significantly decreased the hepatic retention of the antigen-specific T cells,
depletion of Kupffer cells showed opposite effect. Taken together, the antigen
reactive T cells in the liver have higher activities than their counterparts in
the peripheral tissues such as spleen. These data have important clinical
implications for designing immunotherapeutic protocols toward the liver diseases.
PMID- 29338161
TI - Effect of Periodontal Treatment on the Crevicular Level of High-mobility Group
Box 1 and Soluble Triggering Receptor Expressed on Myeloid Cells 1 in Patients
with Chronic Periodontitis.
AB - The present study aimed to compare the levels of high-mobility group box 1(HMGB1)
and soluble triggering receptor expressed on myeloid cells (sTREM1) in the
gingival crevicular fluid (GCF). This cross-sectional cohort trial investigated
two groups of 22 eligible chronic periodontitis and 22 periodontally healthy
individuals (student volunteers) both before and after the periodontal treatment.
GCF was collected from the deepest pockets with clinical attachment loss>=3 mm.
Both groups received oral hygiene instructions, and scaling and root planning
were performed in the test group. Enzyme-linked immunosorbent assay kit (ELISA)
was used to measure the levels of HMGB1 and sTREM1 in GCF samples collected
before and 1 month after non-surgical periodontal treatment. The results showed
that HMGB1 levels were significantly higher in the chronic periodontitis patients
than those of the healthy individuals before treatment (p<0.02) and decreased
significantly after periodontal treatment, which reduced gingival inflammation.
Furthermore, the levels of sTREM1 marker were significantly higher in
periodontitis patients before (p<0.001) and 1 month after treatment than in
healthy individuals (p<0.003) although its crevicular levels decreased after
periodontal therapy in periodontitis group. The higher levels of sTREM1 and HMGB1
cytokines in GCF of periodontitis patients and the significant decrease after the
introduction of the periodontal treatment underlines the importance of HMGB1 and
sTREM1 in pathogenesis of periodontitis.
PMID- 29338162
TI - Endobronchial Lesion in Eosinophilic Granulomatosis with Polyangiitis.
AB - Eosinophilic granulomatosis with polyangiitis is a systemic vasculitis. It could
affect respiratory system, kidney, and central nervous system frequently;
however, all body organs could be involved. Asthma and eosinophilic pneumonia are
predominant manifestations in respiratory system. Bronchoalveolar lavage or lung
biopsy may be used for diagnosis, but endobronchial lesion is not considered as a
manifestation of eosinophilic granulomatosis with polyangiitis. Here we present a
case of eosinophilic granulomatosis with polyangiitis with unusual endobronchial
lesion which was confirmed by endobronchial biopsy.
PMID- 29338163
TI - Kounis Syndrome Induced by Oral Intake of Diclofenac Potassium.
AB - An acute coronary syndrome (ACS) occurring during the course of an allergic
reaction is called Kounis syndrome (KS). The second case of KS induced by
diclofenac potassium (DP) is presented in this report. A 67-year-old man was
brought to our emergency department with the possible diagnosis of anaphylactic
shock by the ambulance staff. It emerged that widespread erythema and pruritus
developed after taking DP. Then, he lost consciousness. Diffuse urticarial
lesions were detected on physical examination at the emergency department. He
complained of chest pain during his observation, and progressive ST segment
elevation was seen in the inferior leads on serial electrocardiograms. His
coronary angiography showed 100% occlusion of the right coronary artery. Then,
KS was diagnosed. The patient was discharged on the second day, and he was doing
well on the control visit 2 weeks later. All allergic reactions may trigger an
ACS so physicians should be aware of KS and always keep that unique clinical
entity in mind to recognize it promptly and direct the therapy at suppressing the
allergic reaction and improving the coronary circulation simultaneously when
encountering a patient with symptoms suggesting an allergic reaction and a
concomitant ACS.
PMID- 29338164
TI - The relation between nonspecific hyperreactivity of the airways and atopic
constitution in asthmatics.
AB - Background/Aim: Hyperreactivity of the airways caused by inflammation in
asthmatics is the most important pathophysiological change. It represents a
suitable ground that in the presence of risk factors and the drivers of asthma,
asthmatic attack occurs. Atopic constitution is one of the most important risk
factors for the development and expression of asthma. The aim of our study was to
investigate the relationship between nonspecific airway hyperreactivity and
atopic constituton in asthmatics. Methods: This retrospective analysis was
conducted considering the results of nonspecific bronchoprovocative test with
histamine, skin tests to inhalant allergens and total IgE levels in the serum of
asthmatic patients with controlled bronchial asthma. The sample consisted of 162
asthmatics examined during one-year period. Results: The examinees were male
asthmatic patients, aged between 18 and 30 years. We found that the examinees
with a pronounced non-specific hyperreactivity had more significant skin reaction
to inhaled allergens and higher levels of total IgE in serum. Conclusion: The
results of our study show that the intensity of airway hyperresponsiveness to
histamine in asthmatics is directly related to atopic constitution.
PMID- 29338165
TI - How Ligands Affect Resistive Switching in Solution-Processed HfO2 Nanoparticle
Assemblies.
AB - Advancement of resistive random access memory (ReRAM) requires fully
understanding the various complex, defect-mediated transport mechanisms to
further improve performance. Although thin-film oxide materials have been
extensively studied, the switching properties of nanoparticle assemblies remain
underexplored due to difficulties in fabricating ordered structures. Here, we
employ a simple flow coating method for the facile deposition of highly ordered
HfO2 nanoparticle nanoribbon assemblies. The resistive switching character of
nanoribbons was determined to correlate directly with the organic capping layer
length of their constituting HfO2 nanoparticles, using oleic acid, dodecanoic
acid, and undecenoic acid as model nanoparticle ligands. Through a systematic
comparison of the forming process, operating set/reset voltages, and resistance
states, we demonstrate a tunable resistive switching response by varying the
ligand type, thus providing a base correlation for solution-processed ReRAM
device fabrication.
PMID- 29338166
TI - Remarkable Effect of Sodium Alginate Aqueous Binder on Anatase TiO2 as High
Performance Anode in Sodium Ion Batteries.
AB - Sodium alginate (SA) is investigated as the aqueous binder to fabricate high
performance, low-cost, environmentally friendly, and durable TiO2 anodes in
sodium-ion batteries (SIBs) for the first time. Compared to the conventional
polyvinylidene difluoride (PVDF) binder, electrodes using SA as the binder
exhibit significant promotion of electrochemical performances. The initial
Coulombic efficiency is as high as 62% at 0.1 C. A remarkable capacity of 180 mAh
g-1 is achieved with no decay after 500 cycles at 1 C. Even at 10 C (3.4 A g-1),
it remains 82 mAh g-1 after 3600 cycles with approximate 100% Coulombic
efficiency. TiO2 electrodes with SA binder display less electrolyte
decomposition, fewer side reactions, high electrochemistry reaction activity,
effective suppression of polarization, and good electrode morphology, which is
ascribed to the rich carboxylic groups, high Young's modulus, and good
electrochemical stability of SA binder.
PMID- 29338167
TI - Nitrogen-Doped Perovskite as a Bifunctional Cathode Catalyst for Rechargeable
Lithium-Oxygen Batteries.
AB - In this work, nitrogen-doped LaNiO3 perovskite was prepared and studied, for the
first time, as a bifunctional electrocatalyst for oxygen cathode in a
rechargeable lithium-oxygen battery. N doping was found to significantly increase
the Ni3+ contents and oxygen vacancies on the bulk surface of the perovskite,
which helped to promote the oxygen reduction reaction and oxygen evolution
reaction of the cathode and, therefore, enabled reversible Li2O2 formation and
decomposition on the cathode surface. As a result, the oxygen cathodes loaded
with N-doped LaNiO3 catalyst showed an improved electrochemical performance in
terms of discharge capacity and cycling stability to promise practical Li-O2
batteries.
PMID- 29338168
TI - Nanocapsules of Magnetic Au Self-Assembly for DNA Migration and Secondary Self
Assembly.
AB - To endow valuable responsiveness to self-assemblies of Au nanoparticles (Au NPs),
the magnetic Au nanoparticles (Au NPs)/C16H33(CH3)3N+[CeCl3Br]- (CTACe) mixtures
were first prepared by using an emulsion self-assembly of a magnetic surfactant,
C16H33(CH3)3N+[CeCl3Br]-. A versatile morphology of self-assemblies of Au NPs
could be controlled by the counterions in surfactants including [CeCl3Br]-,
[FeCl3Br]-, and Br- as well as solvent. In particular, the magnetic counterion,
[CeCl3Br]-, can induce self-growth of Au NPs in an emulsion self-assembly process
due to the oxidability of [CeCl3Br]-. It enhances the rigidity of Au NPs/CTACe
scaffolds template compared with Au NPs/hexadecyltrimethylammonium bromide.
[CeCl3Br]- engaged Au NPs/CTACe with fascinating capability of conglutination and
targeted migration of DNA (150 MUmol/L) under a magnet field. The conglutination
capability of the DNA molecules can increase to 39.8% by adopting the magnetic
strategy when using Au NPs/CTACe as a magnetic booster. Au NPs/CTACe mixtures can
ideally self-assemble to be scaffolds, providing abundant conjugation sites of
surface charges. Magnetic Au NPs/CTACe can serve as a template scaffold to
secondary self-assemble with DNA (40 mmol/L) outside, producing smooth-faced and
hollow DNA nanocapsules. We believe that the creative Au NPs/CTACe/DNA
nanocapsules will extend the biological application field of Au NPs assemblies.
PMID- 29338169
TI - Highly Efficient Soluble Blue Delayed Fluorescent and Hyperfluorescent Organic
Light-Emitting Diodes by Host Engineering.
AB - Solution-processed high-efficiency fluorescent organic light-emitting diodes with
an external quantum efficiency over 18% were developed by engineering a host
material and device structure designed for solution process. A high triplet
energy host material designed for the solution process, (oxybis(3-(tert-butyl)
6,1-phenylene))bis(diphenylphosphine oxide) (DPOBBPE), worked efficiently as the
host of blue fluorescent devices because of good solubility, high
photoluminescence quantum yield, and good film properties. The DPOBBPE host
enabled a high external quantum efficiency of 18.8% in the fluorescent organic
light-emitting diodes by the solution process. Moreover, 25.8% external quantum
efficiency in the soluble blue thermally activated delayed fluorescent devices
was also realized. The 25.8% external quantum efficiency of the DPOBBPE delayed
fluorescent device and 18.8% external quantum efficiency of the fluorescent
device are the highest efficiency values achieved in the solution-processed blue
fluorescent organic light-emitting diodes. Moreover, the solution-processed
fluorescent device showed an improved blue color coordinate of (0.14, 0.20)
compared to (0.17, 0.31) of the delayed fluorescent device.
PMID- 29338170
TI - PEALD of SiO2 and Al2O3 Thin Films on Polypropylene: Investigations of the Film
Growth at the Interface, Stress, and Gas Barrier Properties of Dyads.
AB - A study on the plasma-enhanced atomic layer deposition of amorphous inorganic
oxides SiO2 and Al2O3 on polypropylene (PP) was carried out with respect to
growth taking place at the interface of the polymer substrate and the thin film
employing in situ quartz-crystal microbalance (QCM) experiments. A model layer of
spin-coated PP (scPP) was deposited on QCM crystals prior to depositions to allow
a transfer of findings from QCM studies to industrially applied PP foil. The
influence of precursor choice (trimethylaluminum (TMA) vs [3
(dimethylamino)propyl]-dimethyl aluminum (DMAD)) and of plasma pretreatment on
the monitored QCM response was investigated. Furthermore, dyads of SiO2/Al2O3,
using different Al precursors for the Al2O3 thin-film deposition, were
investigated regarding their barrier performance. Although the growth of SiO2 and
Al2O3 from TMA on scPP is significantly hindered if no oxygen plasma pretreatment
is applied to the scPP prior to depositions, the DMAD process was found to yield
comparable Al2O3 growth directly on scPP similar to that found on a bare QCM
crystal. From this, the interface formed between the Al2O3 and the PP substrate
is suggested to be different for the two precursors TMA and DMAD due to different
growth modes. Furthermore, the residual stress of the thin films influences the
barrier properties of SiO2/Al2O3 dyads. Dyads composed of 5 nm Al2O3 (DMAD) + 5
nm SiO2 exhibit an oxygen transmission rate (OTR) of 57.4 cm3 m-2 day-1, which
correlates with a barrier improvement factor of 24 against 5 when Al2O3 from TMA
is applied.
PMID- 29338171
TI - Flexible Capacitive Piezoelectric Sensor with Vertically Aligned Ultralong GaN
Wires.
AB - We report a simple and scalable fabrication process of flexible capacitive
piezoelectric sensors using vertically aligned gallium nitride (GaN) wires as
well as their physical principles of operation. The as-grown N-polar GaN wires
obtained by self-catalyst metal-organic vapor phase epitaxy are embedded into a
polydimethylsiloxane (PDMS) matrix and directly peeled off from the sapphire
substrate before metallic electrode contacting. This geometry provides an
efficient control of the wire orientation and an additive contribution of the
individual piezoelectric signals. The device output voltage and efficiency are
studied by finite element calculations for compression mechanical loading as a
function of the wire geometrical growth parameters (length and density). We
demonstrate that the voltage output level and sensitivity increases as a function
of the wire length and that a conical shape is not mandatory for potential
generation as it was the case for horizontally assembled devices. The optimal
design to improve the overall device response is also optimized in terms of wire
positioning inside PDMS, wire density, and total device thickness. Following the
results of these calculations, we have fabricated experimental devices exhibiting
outputs of several volts with a very good reliability under cyclic mechanical
excitation.
PMID- 29338172
TI - Activation of Nrf2 and Hypoxic Adaptive Response Contribute to Neuroprotection
Elicited by Phenylhydroxamic Acid Selective HDAC6 Inhibitors.
AB - Activation of HIF-1alpha and Nrf2 is a primary component of cellular response to
oxidative stress, and activation of HIF-1alpha and Nrf2 provides neuroprotection
in models of neurodegenerative disorders, including ischemic stroke, Alzheimer's
and Parkinson's diseases. Screening a library of CNS-targeted drugs using novel
reporters for HIF-1alpha and Nrf2 elevation in neuronal cells revealed histone
deacetylase (HDAC) inhibitors as potential activators of these pathways. We
report the identification of phenylhydroxamates as single agents exhibiting
tripartite inhibition of HDAC6, inhibition of HIF-1 prolyl hydroxylase (PHD), and
activation of Nrf2. Two superior tripartite agents, ING-6 and ING-66, showed
neuroprotection against various cellular insults, associated with stabilization
of both Nrf2 and HIF-1, and expression of their respective target genes in vitro
and in vivo. Discovery of the innate ability of phenylhydroxamate HDAC inhibitors
to activate Nrf2 and HIF provides a novel route to multifunctional
neuroprotective agents and cautions against HDAC6 selective inhibitors as
chemical probes of specific HDAC isoform function.
PMID- 29338173
TI - Smartphone-Based VOC Sensor Using Colorimetric Polydiacetylenes.
AB - Owing to a unique colorimetric (typically blue-to-red) feature upon environmental
stimulation, polydiacetylenes (PDAs) have been actively employed in chemosensor
systems. We developed a highly accurate and simple volatile organic compound
(VOC) sensor system that can be operated using a conventional smartphone. The
procedure begins with forming an array of four different PDAs on conventional
paper using inkjet printing of four corresponding diacetylenes followed by
photopolymerization. A database of color changes (i.e., red and hue values) is
then constructed on the basis of different solvatochromic responses of the 4 PDAs
to 11 organic solvents. Exposure of the PDA array to an unknown solvent promotes
color changes, which are imaged using a smartphone camera and analyzed using the
app. A comparison of the color changes to the database promoted by the 11
solvents enables the smartphone app to identify the unknown solvent with 100%
accuracy. Additionally, it was demonstrated that the PDA array sensor was
sufficiently sensitive to accurately detect the 11 VOC gases.
PMID- 29338174
TI - Solution-Processable ZnO/Carbon Quantum Dots Electron Extraction Layer for Highly
Efficient Polymer Solar Cells.
AB - In this work, we report the effort to develop high-efficiency inverted polymer
solar cells (PSCs) by applying a solution-processable bilayer ZnO/carbon quantum
dots (C-QDs) electron extraction layer (EEL). It is shown that the use of the
bilayer EEL helps to suppress the exciton quenching by passivating the ZnO
surface defects in the EEL, leading to an enhanced exciton dissociation, reduced
charge recombination and more efficient charge extraction probability, and
thereby achieving high power conversion efficiency (PCE). The inverted PSCs,
based on the blend of poly{4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5
b']dithiophene-2,6-diyl-alt-3-fluoro-2-[(2-ethylhexyl)carbonyl]thieno[3,4
b]thiophene-4,6-diyl} and [6,6]-phenyl C71-butyric acid methyl ester, possess a
significant improvement in PCE of ~9.64%, which is >27% higher than that of a
control cell (~7.59%). The use of a bilayer ZnO/C-QD EEL offers a promising
approach for attaining high-efficiency inverted PSCs.
PMID- 29338175
TI - Limitations of Cs3Bi2I9 as Lead-Free Photovoltaic Absorber Materials.
AB - Lead (Pb) halide perovskites have attracted tremendous attention in recent years
because of their rich optoelectronic properties, which have resulted in more than
22% power conversion efficient photovoltaics (PVs). Nevertheless, Pb-metal
toxicity remains a huge hurdle for extensive applications of these compounds.
Thus, alternative compounds with similar optoelectronic properties need to be
developed. Bismuth possesses electronic structure similar to that of lead with
the presence of ns2 electrons that exhibit rich structural variety as well as
interesting optical and electronic properties. Herein, we critically assess
Cs3Bi2I9 as a candidate for thin-film solar cell absorber. Despite a reasonable
optical band gap (~2 eV) and absorption coefficient, the power conversion
efficiency of the Cs3Bi2I9 mesoscopic solar cells was found to be severely
lacking, limited by the poor photocurrent density. The efficiency of the Cs3Bi2I9
solar cell can be slightly improved by changing the stoichiometry of the
precursor solutions, which is most probably due to the reduction in nonradiative
defects as evident from our single-crystal photoluminescence spectroscopy.
However, detailed investigations on pristine Cs3Bi2I9 reveal that zero
dimensional molecular crystal structure remains one of the main bottlenecks in
achieving high performance. On the basis of our comprehensive studies, we have
proposed that a continuous network of three-dimensional crystal structure should
be another major criterion in addition to proper band gap and suitable optical
properties of the future PV compounds.
PMID- 29338176
TI - Polystyrene-block-Poly(ionic liquid) Copolymers as Work Function Modifiers in
Inverted Organic Photovoltaic Cells.
AB - Interfacial layers play a critical role in building up the Ohmic contact between
electrodes and functional layers in organic photovoltaic (OPV) solar cells. These
layers are based on either inorganic oxides (ZnO and TiO2) or water-soluble
organic polymers such as poly[(9,9-dioctyl-2,7-fluorene)-alt-(9,9-bis(3'-(N,N
dimethylamino)propyl)-2,7-fluorene)] and polyethylenimine ethoxylated (PEIE). In
this work, we have developed a series of novel poly(ionic liquid) nonconjugated
block copolymers for improving the performance of inverted OPV cells by using
them as work function modifiers of the indium tin oxide (ITO) cathode. Four
nonconjugated polyelectrolytes (n-CPEs) based on polystyrene and imidazolium
poly(ionic liquid) (PSImCl) were synthesized by reversible addition-fragmentation
chain transfer polymerization. The ratio of hydrophobic/hydrophilic block
copolymers was varied depending on the ratio of polystyrene to the PSImCl block.
The ionic density, which controls the work function of the electrode by forming
an interfacial dipole between the electrode and the block copolymers, was easily
tuned by simply changing the PSImCl molar ratio. The inverted OPV device with the
ITO/PS29-b-PSImCl60 cathode achieved the best power conversion efficiency (PCE)
of 7.55% among the synthesized block copolymers, exhibiting an even higher PCE
than that of the reference OPV device with PEIE (7.30%). Furthermore, the surface
properties of the block copolymers films were investigated by contact angle
measurements to explore the influence of the controlled hydrophobic/hydrophilic
characters on the device performances.
PMID- 29338177
TI - Novel Alkali Activation of Titanium Substrates To Grow Thick and Covalently Bound
PMMA Layers.
AB - Titanium (Ti) is the most widely used metal in biomedical applications because of
its biocompatibility; however, the significant difference in the mechanical
properties between Ti and the surrounding tissues results in stress shielding
which is detrimental for load-bearing tissues. In the current study, to attenuate
the stress shielding effect, a new processing route was developed. It aimed at
growing thick poly(methyl methacrylate) (PMMA) layers grafted on Ti substrates to
incorporate a polymer component on Ti implants. However, the currently available
methods do not allow the development of thick polymeric layers, reducing
significantly their potential uses. The proposed route consists of an alkali
activation of Ti substrates followed by a surface-initiated atom transfer radical
polymerization using a phosphonic acid derivative as a coupling agent and a
polymerization initiator and malononitrile as a polymerization activator. The
average thickness of the grown PMMA layers is approximately 1.9 MUm. The Ti
activation-performed in a NaOH solution-leads to a porous sodium titanate
interlayer with a hierarchical structure and an open microporosity. It promotes
the covalent grafting reaction because of high hydroxyl groups' content and
enables establishing a further mechanical interlocking between the growing PMMA
layer and the Ti substrate. As a result, the produced graduated structure
possesses high Ti/PMMA adhesion strength (~260 MPa). Moreover, the PMMA layer is
(i) thicker compared to those obtained with the previously reported techniques
(~1.9 MUm), (ii) stable in a simulated body fluid solution, and (iii)
biocompatible. This strategy opens new opportunities toward hybrid prosthesis
with adjustable mechanical properties with respect to host bone properties for
personalized medicines.
PMID- 29338178
TI - DNA Damage and Apoptosis Induction in Cancer Cells by Chemically Engineered
Thiolated Riboflavin Gold Nanoassembly.
AB - Herein we have engineered a smart nuclear targeting thiol-modified riboflavin
gold nano assembly, RfS@AuNPs, which accumulates selectively in the nucleus
without any nuclear-targeting peptides (NLS/RGD) and shows photophysically in
vitro DNA intercalation. A theoretical model using Molecular Dynamics has been
developed to probe the mechanism of formation and stability as well as dynamics
of the RfS@AuNPs in aqueous solution and within the DNA microenvironment. The
RfS@AuNPs facilitate the binucleated cell formation that is reflected in the
significant increase of DNA damage marker, gamma-H2AX as well as the arrest of
most of the HeLa cells at the pre-G1 phase indicating cell death. Moreover, a
significant upregulation of apoptotic markers confirms that the cell death occurs
through the apoptotic pathway. Analyses of the microarray gene expression of
RfS@AuNPs treated HeLa cells show significant alterations in vital biological
processes necessary for cell survival. Taken together, our study reports a unique
nuclear targeting mechanism through targeting the riboflavin receptors, which are
upregulated in cancer cells and induce apoptosis in the targeted cells.
PMID- 29338179
TI - Ligand-Switchable Micellar Nanocarriers for Prolonging Circulation Time and
Enhancing Targeting Efficiency.
AB - Targeted drug delivery of nanomedicines offered a promising strategy to improve
the tumor accumulation and reduce the side effects of chemotherapeutics. However,
undesired recognition of the targeting ligands on the surface of nanocarriers by
immune systems or normal tissues decreased the circulation time and reduced the
targeting efficiency. Here, we developed a ligand-switchable micellar nanocarrier
that can hide the targeting ligands when circulating in the bloodstream and
expose them on the surface when entering the tumor microenvironments. With the
ligand-switching capability, the nanocarrier achieved a 66% longer blood
circulation half-life and a 23% higher tumor accumulation than the nanocarrier
with targeting ligands on the surface. This targeting strategy could serve as a
universal approach to improve the targeting efficiency for nanomedicines.
PMID- 29338180
TI - Hollow Echinus-like PdCuCo Alloy for Superior Efficient Catalysis of Ethanol.
AB - Large-scale preparation of hollow echinus-like PdCuCo alloy nanostructures
(HENSs) with a high surface area-to-volume ratio, rich active sites, and
relatively efficient catalytic activity has attracted considerable research
interest. Herein, we present an economic and facile approach to synthesize HENSs
by galvanic exchange reactions using Co nanospheres as sacrificial templates.
Moreover, the catalytic activity could be adjusted via changing the composition
of the catalyst. The composition, morphology, and crystal structure of the as
obtained nanomaterials are characterized by various techniques, such as
inductively coupled plasma atomic emission spectrometry, transmission electron
microscopy, and X-ray diffraction. Electrochemical catalytic measurement results
prove that the Pd75Cu8Co3 catalyst obtained under optimal preparation conditions
exhibits 10-fold higher activity for ethanol oxidation in comparison with the
commercially available 20% Pd/C catalyst. The eminent performance of the
Pd75Cu8Co3 electrochemical catalyst could be ascribed to the peculiar echinus
like nanostructures.
PMID- 29338181
TI - Attaining Melt Processing of Complementary Semiconducting Polymer Blends at 130
degrees C via Side-Chain Engineering.
AB - Complementary semiconducting polymer blends (c-SPBs) have been proposed and
tested to achieve melt-processed high-performance organic field-effect
transistors (OFETs). Prior to this study, melt processing requires temperatures
as high as 180 degrees C. To implement this technique into low-cost and large
area thin-film manufacturing for flexible organic electronics, semiconducting
materials meltable at temperatures tolerable by ubiquitous plastic substrates are
still needed. We report here the design and melt processing of a c-SPB consisting
of a matrix polymer (DPP-C5) and its fully conjugated analogue. By utilizing a
siloxane-terminated alkyl chain and a branched alkyl chain as solubilizing
groups, the matrix polymer DPP-C5 presents a melting temperature of 115 degrees
C. The resulting c-SPB containing as low as 5% of the fully conjugated polymer
could be melt-processed at 130 degrees C. The obtained OFET devices exhibit hole
mobility approaching 1.0 cm2/(V s), threshold voltages below 5 V, and ION/IOFF
around 105. This combination of efficient charge-carrier transport and
considerably low processing temperatures bode well for melt processing of
semiconducting polymer-based organic electronics.
PMID- 29338182
TI - "Infinite Sensitivity" of Black Silicon Ammonia Sensor Achieved by Optical and
Electric Dual Drives.
AB - The microstructured and hyperdoped silicon as a superior photoelectric and
photovoltaic material is first studied as a gas-sensing material. The material is
prepared by femtosecond-laser irradiation on selenium-coated silicon and then
fabricated as a conductive gas sensor, targeting ammonia. At room temperature,
the sensitivity, response time, repeatability, distinguishability, selectivity,
and natural aging effect of the sensor have been systematically studied. Results
show that such black silicon has good potential for application as an ammonia
sensing material. On the basis of its unique optoelectronic properties, an
additional optical drive is proposed for the formation of an optical and electric
dual-driven sensor, which is achieved by asymmetric light illumination between
the two electrode regions. In a certain range of applied voltage, the sensitivity
is enhanced dramatically and even tends to be infinite. For the aged device with
degraded sensitivity, a two-order increment is obtained for 500 ppm of NH3 under
the extra optical drive. A mechanism based on Dember effect is proposed for
explaining such a phenomenon.
PMID- 29338183
TI - Plasma-Induced Oxygen Vacancies in Urchin-Like Anatase Titania Coated by Carbon
for Excellent Sodium-Ion Battery Anodes.
AB - The incorporation of oxygen vacancies in anatase TiO2 has been studied as a
promising way to accelerate the transport of electrons and Na+ ions, which is
important for achieving excellent electrochemical properties for anatase TiO2.
However, wittingly introducing oxygen vacancies in anatase TiO2 for sodium-ion
anodes by a facile and effective method is still a challenge. In this work, we
report an innovative method to introduce oxygen vacancies into the urchin-like N
doped carbon coated anatase TiO2 (NC-DTO) by a facile plasma treatment. The
superiorities of the oxygen vacancies combined with the conductive N-doped carbon
coating enable the obtained NC-DTO of greatly improved sodium storage
performance. When served as the anode for sodium-ion batteries, the NC-DTO
electrode shows superior electrochemical performance (capacity: 272 mA h g-1 at
0.25 C, capacity retention: 98.8% after 5000 cycles at 10 C, as well as ultrahigh
capacity: 150 mA h g-1 at 15 C). Density functional theory calculations combined
with experimental results suggest that considerably improved sodium storage
performance of NC-DTO is due to the enhanced electronic conductivity from the N
doped carbon layer as well as narrowed band gap and lowered sodiation energy
barrier from the introduction of oxygen vacancies. This work highlights that
introducing oxygen vacancies into TiO2 by plasma is a promising method to enhance
the electrochemical property of TiO2, which also can be applied to different
metal oxides for energy storage devices.
PMID- 29338184
TI - Design of pH-Sensitive Nanovesicles via Cholesterol Analogue Incorporation for
Improving in Vivo Delivery of Chemotherapeutics.
AB - pH-responsive polymersomes have emerged as promising nanocarriers for antitumor
drugs to realize their fast release and action in a weakly acidic
microenvironment of tumor cells. Herein, however, we designed a remarkably pH
responsive polymersome self-assembled from amphiphilic benzimidazole-based
polyphosphazenes via the incorporation of cholesteryl hemisuccinate (CholHS), a
type of cholesteric molecule, into the polymersome bilayers to inhibit the drug
release during blood circulation. Actually, unwanted premature drug leakage
before arriving at the acidic tumor site has become a serious problem for
polymersomes encapsulating water-soluble drugs, especially when the drug loading
is at a high level, thus limiting the therapeutic efficacy. In this study,
polymersomes displayed high loading capability of doxorubicin hydrochloride as
12.83%. More importantly, CholHS incorporation decreased the membrane
permeability of the polymersome and effectively retarded the cargo release under
physiological conditions but induced the fast drug-release rate at pH 5.5,
demonstrating a more remarkably acid-responsive release behavior when compared to
that of the CholHS-free polymersomes. Further in vivo investigations including
pharmacokinetic and antitumor activity studies verified the extended circulation
time and enhanced antitumor efficacy of the drug-loaded CholHS-incorporated
polymersomes.
PMID- 29338185
TI - Injectable and Thermosensitive Hydrogel and PDLLA Electrospun Nanofiber Membrane
Composites for Guided Spinal Fusion.
AB - Spinal fusion is the classic treatment to achieve spinal stability for the
treatment of the spinal disease. Generally, spinal fusion still has to combine a
certain of bone matrix for promoting bone formation to achieve the desired fusion
effect based on the surgery, including the traditional bone matrix, such as the
autologous bone, allografts and xenografts. Nevertheless, some problems still
existed such as the immunogenic problems, the secondary wound, and pathogenic
transfer and so on. Here the injectable thermosensitive hydrogel could substitute
to avoid the problems as a potential biological scaffold for tissue engineering.
Once injected, they could fill in the irregular-shaped cavity and change to a gel
state at physiological temperature. We wanted to design the collagen/n-HA/BMP
2@PCEC/PECE hydrogel composites based on previous work about collagen/n-HA/PECE
hydrogel to exhibit better performance in guiding spinal fusion because of the
addition of BMP-2@PCEC nanoparticles (PCEC, PCL-PEG-PCL). However, when the
hydrogels were injected, one of the surfaces was in contact with the spine, but
others were in contact with soft tissue like muscles and fascia. The release
behavior was the same at the different surfaces, so the factors could be released
into the soft tissue, and it may then be consumed or lead to ectopic bone
formation. The hydrogel composites should be improved to adjust the direction of
the releaser behavior. In consequence, we wrapped an electrostatic spinning
nanofiber membrane possessing hydrophobicity around the hydrogels. In this study,
we developed a system that the collagen/n-HA/BMP-2@PCEC/PECE hydrogels were
wrapped with the hydrophobicity PDLLA electrospun nanofiber membrane, setting up
a barrier between the hydrogels and the soft tissue. The system could exhibit
biocompatibility, preventing the factors from escaping to keep their retention in
the needed places of osteogenesis; the results demonstrated that it showed an
excellent effect on spinal fusion.
PMID- 29338186
TI - Editors' Favorites of 2017.
PMID- 29338188
TI - Special Issue on Precision Medicine for Brain Cancer in ACS Chemical
Neuroscience.
PMID- 29338189
TI - Three-Phase Morphology Evolution in Sequentially Solution-Processed Polymer
Photodetector: Toward Low Dark Current and High Photodetectivity.
AB - Sequentially solution-processed polymer photodetectors (SSP PPDs) based on poly(3
hexylthiophene-2,5-diyl) (P3HT)/[6,6]-phenyl C71-butyric acid methyl ester
(PC71BM) are fabricated by depositing the top layers of PC71BM from an
appropriate cosolvent of 2-chlorophenol (2-CP)/o-dichlorobenzene (ODCB) onto the
predeposited bottom layers of P3HT. By adjusting the ratio of 2-CP/ODCB in the
top PC71BM layers, the resulting SSP PPD shows a decreased dark current and an
increased photocurrent, leading to a maximum detectivity of 1.23 * 1012 Jones at
a wavelength of 550 nm. This value is 5.3-fold higher than that of the
conventional bulk heterojunction PPD. Morphology studies reveal that the PC71BM
partially penetrates the predeposited P3HT layer during the spin-coating process,
resulting in an optimal three-phase morphology with one well-mixed interdiffusion
P3HT/PC71BM phase in the middle of the bulk and two pure phases of P3HT and
PC71BM at the two electrode sides. We show that the pure phases form high
Schottky barriers (>2.0 eV) at the active layer/electrodes interface and
efficiently block unfavorable reverse charge carrier injection by significantly
decreasing the dark current. The interdiffussion phase enlarges the donor
acceptor interfacial area leading to a large photocurrent. We also reveal that
the improved performance of SSP PPDs is also due to the enhanced optical
absorption, improved P3HT crystallinity, increased charge carrier mobilities, and
suppressed bimolecular recombination.
PMID- 29338190
TI - Cancer Cell Membrane-Biomimetic Nanoprobes with Two-Photon Excitation and Near
Infrared Emission for Intravital Tumor Fluorescence Imaging.
AB - Biomimetic fluorescent nanoprobes capable of emitting near-infrared (NIR)
fluorescence (lambdamax ~ 720 nm) upon excitation of 800 nm light were developed.
The key conjugated polymer enabled two-photon absorption and Forster resonance
energy transfer (FRET) processes within the nanoprobes, which imparted the
nanoprobes with ideal NIR-incoming-NIR-outgoing fluorescence features. The cancer
cell membrane (CM) coating endowed these nanoprobes with perfect biocompatibility
and highly specific targeting ability to homologous tumors. It was believed that
CM encapsulation provided an additional protecting layer for the photoactive
components residing in the core of nanoprobes for retaining their intrinsic
fluorescing ability in the physiological milieu. The long-term structural
integrity, excellent photostability (fluorescence decrease <10% upon 30 min
illumination of 800 nm pulse laser), high NIR fluorescence quantum yield (~20%),
and long in vivo circulation time of the target nanoprobes were also confirmed.
The ability of these feature-packed nanoprobes for circumventing the challenges
of absorption and light scattering caused by cellular structures and tissues was
definitely confirmed via in vivo and in vitro experiments. The superior
performances of these nanoprobes in terms of fluorescence signaling as well as
targeting specificity were verified in intravital fluorescence imaging on tumor
bearing model mice. Specifically, these nanoprobes unequivocally enabled high
resolution visualization of the fine heterogeneous architectures of intravital
tumor tissue, which proclaims the great potential of this type of probe for high
contrast fluorescence detection of thick biological samples in practical
applications.
PMID- 29338192
TI - Under-Oil Switchable Superhydrophobicity to Superhydrophilicity Transition on
TiO2 Nanotube Arrays.
AB - Recently, smart interfacial materials that can reversibly transit between the
superhydrophobicity and superhydrophilicity have aroused much attention. However,
all present performances happen in air, and to realize such a smart transition in
complex environments, such as oil, is still a challenge. Herein, TiO2 nanotube
arrays with switchable transition between the superhydrophobicity and
superhydrophilicity in oil are reported. The switching can be observed by
alternation of UV irradiation and heating process, and the smart controllability
can be ascribed to the cooperative effect between the surface nanostructures and
the chemical composition variation. By using the controllable wetting
performances, some applications such as under-oil droplet-based microreaction and
water-removal from oil were demonstrated on our surface. This paper reports a
surface with smart water wettability in oil, which could start some fresh ideas
for wetting control on interfacial materials.
PMID- 29338191
TI - Conjugate Polyplexes with Anti-Invasive Properties and Improved siRNA Delivery In
Vivo.
AB - This study reports on a simple method to prepare siRNA-polycation conjugate
polyplexes by in situ thiol-disulfide exchange reaction. The conjugate polyplexes
are prepared using thiol-terminated siRNA and a bioreducible branched
polycationic inhibitor of the CXCR4 chemokine receptor (rPAMD). The rPAMD-SS
siRNA conjugate polyplexes exhibit improved colloidal stability and resistance
against disassembly with heparin, serum, and physiological salt concentrations
when compared with control conventional rPAMD/siRNA polyplexes. Coating the
polyplexes with human serum albumin masks the positive surface charge and
contributes to the enhanced in vitro gene silencing and improved safety in vivo.
The conjugate polyplexes display improved in vivo reporter gene silencing
following intravenous injection in tumor-bearing mice. Because the conjugate
polyplexes retained the ability of rPAMD to inhibit CXCR4 and restrict cancer
cell invasion, the developed systems show promise for future combination anti
metastatic siRNA therapies of cancer.
PMID- 29338193
TI - Induction of Chirality in Two-Dimensional Nanomaterials: Chiral 2D MoS2
Nanostructures.
AB - Two-dimensional (2D) nanomaterials have been intensively investigated due to
their interesting properties and range of potential applications. Although most
research has focused on graphene, atomic layered transition metal dichalcogenides
(TMDs) and particularly MoS2 have gathered much deserved attention recently.
Here, we report the induction of chirality into 2D chiral nanomaterials by
carrying out liquid exfoliation of MoS2 in the presence of chiral ligands
(cysteine and penicillamine) in water. This processing resulted in exfoliated
chiral 2D MoS2 nanosheets showing strong circular dichroism signals, which were
far past the onset of the original chiral ligand signals. Using theoretical
modeling, we demonstrated that the chiral nature of MoS2 nanosheets is related to
the presence of chiral ligands causing preferential folding of the MoS2 sheets.
There was an excellent match between the theoretically calculated and
experimental spectra. We believe that, due to their high aspect ratio planar
morphology, chiral 2D nanomaterials could offer great opportunities for the
development of chiroptical sensors, materials, and devices for valleytronics and
other potential applications. In addition, chirality plays a key role in many
chemical and biological systems, with chiral molecules and materials critical for
the further development of biopharmaceuticals and fine chemicals, and this
research therefore should have a strong impact on relevant areas of science and
technology such as nanobiotechnology, nanomedicine, and nanotoxicology.
PMID- 29338194
TI - Sequential and Selective Detection of Two Molecules with a Single Solid-Contact
Chronopotentiometric Ion-Selective Electrode.
AB - A polymeric membrane ion-selective electrode (ISE) is typically designed for the
determination of one specific ion using a conventional method. In this work, we
demonstrate a simple, versatile, and sensitive platform for simultaneous
detection of two molecules with a single ISE. Under a series of periodic
galvanostatic polarization, a solid-contact ISE without ion exchanger properties
under zero-current conditions has been successfully used for simultaneous
detection of two opposite charged ions with high sensitivity, good selectivity,
and fast reversibility. By integration of biorecognition elements with the
potentiometric measurement, highly sensitive and selective detection of a broad
range of different molecular targets can be predicted. As a proof of concept, a
potentiometric genosensor based on magnetic beads-enzyme sandwich assay has been
designed for sensitive and selective detection of pathogenic bacteria Escherichia
coli O157:H7 and Staphylococcus aureus. Under optimal conditions, two bacteria
nucleic acid sequences can be detected simultaneously with high sensitivity and
good selectivity by using a single solid-contact potentiometric ISE. The
detection limits of Escherichia coli O157:H7 DNA and Staphylococcus aureus DNA
are 120 and 54 fM (3sigma), respectively. Because of its simplicity, this
potentiometric technique based on ISE can be an attractive tool or detector to
perform two analyte measurements.
PMID- 29338195
TI - Mesoporous Silica Thin Films for Improved Electrochemical Detection of Paraquat.
AB - An electrochemical method was developed for rapid and sensitive detection of the
herbicide paraquat in aqueous samples using mesoporous silica thin film modified
glassy carbon electrodes (GCE). Vertically aligned mesoporous silica thin films
were deposited onto GCE by electrochemically assisted self-assembly (EASA).
Cyclic voltammetry revealed effective response to the cationic analyte (while
rejecting anions) thanks to the charge selectivity exhibited by the negatively
charged mesoporous channels. Square wave voltametry (SWV) was then used to detect
paraquat via its one electron reduction process. Influence of various
experimental parameters (i.e., pH, electrolyte concentration, and nature of
electrolyte anions) on sensitivity was investigated and discussed with respect to
the mesopore characteristics and accumulation efficiency, pointing out the key
role of charge distribution in such confined spaces on these processes.
Calibration plots for paraquat concentration ranging from 10 nM to 10 MUM were
constructed at mesoporous silica modified GCE which were linear with increasing
paraquat concentration, showing dramatically enhanced sensitivity (almost 30
times) as compared to nonmodified electrodes. Finally, real samples from Meuse
River (France) spiked with paraquat, without any pretreatment (except
filtration), were analyzed by SWV, revealing the possible detection of paraquat
at very low concentration (10-50 nM). Limit of detection (LOD) calculated from
real sample analysis was found to be 12 nM, which is well below the permissible
limits of paraquat in drinking water (40-400 nM) in various countries.
PMID- 29338196
TI - Method for High Frequency Underway N2 Fixation Measurements: Flow-Through
Incubation Acetylene Reduction Assays by Cavity Ring Down Laser Absorption
Spectroscopy (FARACAS).
AB - Because of the difficulty in resolving the large variability of N2 fixation with
current methods which rely on discrete sampling, the development of new methods
for high-resolution measurements is highly desirable. We present a new method for
high-frequency measurements of aquatic N2 fixation by continuous flow-through
incubations and spectral monitoring of the acetylene (C2H2, a substrate analog
for N2) reduction to ethylene (C2H4). In this method, named Flow-through
Incubation Acetylene Reduction Assays by Cavity Ring-Down Laser Absorption
Spectroscopy (FARACAS), dissolved C2H2 is continuously admixed with seawater
upstream of a continuous-flow stirred-tank reactor (CFSR) in which C2H2 reduction
takes place. Downstream of the flow-through incubator, the C2H4 gas is stripped
using a bubble column contactor and circulated with a diaphragm pump into a
wavelength-scanned cavity ring down laser absorption spectrometer (CRDS). Our
method provides high-resolution and precise mapping of aquatic N2 fixation, its
diel cycle, and its response to environmental gradients, and can be adapted to
measure other biological processes. The short-duration of the flow-through
incubations without preconcentration of cells minimizes potential artifacts such
as bottle containment effects while providing near real-time estimates for
adaptive sampling. We expect that our new method will improve the
characterization of the biogeography and kinetics of aquatic N2 fixation rates.
PMID- 29338197
TI - Modification of Vapor Phase Concentrations in MoS2 Growth Using a NiO Foam
Barrier.
AB - Single-layer molybdenum disulfide (MoS2) has attracted significant attention due
to its electronic and physical properties, with much effort invested toward
obtaining large-area high-quality monolayer MoS2 films. In this work, we
demonstrate a reactive-barrier-based approach to achieve growth of highly
homogeneous single-layer MoS2 on sapphire by the use of a nickel oxide foam
barrier during chemical vapor deposition. Due to the reactivity of the NiO
barrier with MoO3, the concentration of precursors reaching the substrate and
thus nucleation density is effectively reduced, allowing grain sizes of up to 170
MUm and continuous monolayers on the centimeter length scale being obtained. The
quality of the monolayer is further revealed by angle-resolved photoemission
spectroscopy measurement by observation of a very well resolved electronic band
structure and spin-orbit splitting of the bands at room temperature with only two
major domain orientations, indicating the successful growth of a highly
crystalline and well-oriented MoS2 monolayer.
PMID- 29338198
TI - Atomic Resolution Imaging of Nanoscale Chemical Expansion in PrxCe1-xO2-delta
during In Situ Heating.
AB - Thin film nonstoichiometric oxides enable many high-temperature applications
including solid oxide fuel cells, actuators, and catalysis. Large concentrations
of point defects (particularly, oxygen vacancies) enable fast ionic conductivity
or gas exchange kinetics in these materials but also manifest as coupling between
lattice volume and chemical composition. This chemical expansion may be either
detrimental or useful, especially in thin film devices that may exhibit enhanced
performance through strain engineering or decreased operating temperatures.
However, thin film nonstoichiometric oxides can differ from bulk counterparts in
terms of operando defect concentrations, transport properties, and mechanical
properties. Here, we present an in situ investigation of atomic-scale chemical
expansion in PrxCe1-xO2-delta (PCO), a mixed ionic-electronic conducting oxide
relevant to electrochemical energy conversion and high-temperature actuation.
Through a combination of electron energy loss spectroscopy and transmission
electron microscopy with in situ heating, we characterized chemical strains and
changes in oxidation state in cross sections of PCO films grown on yttria
stabilized zirconia (YSZ) at temperatures reaching 650 degrees C. We quantified,
both statically and dynamically, the nanoscale chemical expansion induced by
changes in PCO redox state as a function of position and direction relative to
the film-substrate interface. Additionally, we observed dislocations at the film
substrate interface, as well as reduced cation localization to threading defects
within PCO films. These results illustrate several key aspects of atomic-scale
structure and mechanical deformation in nonstoichiometric oxide films that
clarify distinctions between films and bulk counterparts and that hold several
implications for operando chemical expansion or "breathing" of such oxide films.
PMID- 29338199
TI - Enediyne-Comprising Amino Aldehydes in the Passerini Reaction.
AB - Multicomponent reactions represent a highly efficient approach to a broad
spectrum of structurally diverse compounds starting from simple and affordable
compounds. A focused library of tweezers-like compounds is prepared by employing
the multicomponent Passerini reaction comprising enediyne-derived amino
aldehydes. The reaction proceeds under mild conditions yielding Passerini
products in good to excellent yields. Postcondensation modifications of Passerini
products are demonstrated through a simple deprotection/coupling approach
comprising amino functionality, furnishing enediyne cores with highly decorated
arms.
PMID- 29338200
TI - Solid-Phase Synthesis of Oligopeptides Containing Sterically Hindered Amino Acids
on Nonswellable Resin Using 3-Nitro-1,2,4-triazol-1-yl-tris(pyrrolidin-1
yl)phosphonium Hexafluorophosphate (PyNTP) as the Condensing Reagent.
AB - Peptides are still difficult to synthesize when they contain sterically hindered
amino acids, such as alpha,alpha-disubstituted amino acids and N-substituted
amino acids. In this study, solid-phase syntheses of oligopeptides containing
multiple alpha-aminoisobutyric acid (Aib) residues were performed in high yields
by using a nonswellable resin as the solid-support and 3-nitro-1,2,4-triazol-1-yl
tris(pyrrolidin-1-yl)phosphonium hexafluorophosphate (PyNTP) as the condensing
reagent.
PMID- 29338201
TI - Self-Assembly of Spider Silk-Fusion Proteins Comprising Enzymatic and
Fluorescence Activity.
AB - The recombinant spider silk protein eADF4(C16) was genetically fused either with
esterase 2 (EST2) or green fluorescent protein (GFP). The fusions EST-eADF4(C16)
and GFP-eADF4(C16) were spectroscopically investigated and showed native
structures of EST and GFP. The structural integrity was confirmed by the
enzymatic activity of EST and the fluorescence of GFP. The spider silk moiety
retained its intrinsically unstructured conformation in solution and the self
assembly into either nanofibrils or nanoparticles could be controlled by the
concentration of phosphate. Particles, however, showed significantly lower
activity of the EST and GFP domains likely caused by a steric hindrance. However,
upon self-assembly of EST-eADF4(C16) and GFP-eADF4(C16) into fibrils the protein
activities were retained. In general, the fusion of globular enzymes with the
spider silk domain allows the generation of fibrous biomaterials with catalytic
or light emitting properties.
PMID- 29338202
TI - Nanoscale Domain Imaging of All-Polymer Organic Solar Cells by Photo-Induced
Force Microscopy.
AB - Rapid nanoscale imaging of the bulk heterojunction layer in organic solar cells
is essential to the continued development of high-performance devices.
Unfortunately, commonly used imaging techniques such as tunneling electron
microscopy (TEM) and atomic force microscopy (AFM) suffer from significant
drawbacks. For instance, assuming domain identity from phase contrast or
topographical features can lead to inaccurate morphological conclusions. Here we
demonstrate a technique known as photo-induced force microscopy (PiFM) for
imaging organic solar cell bulk heterojunctions with nanoscale chemical
specificity. PiFM is a relatively recent scanning probe microscopy technique that
combines an AFM tip with a tunable infrared laser to induce a dipole for chemical
imaging. Coupling the nanometer resolution of AFM with the chemical specificity
of a tuned IR laser, we are able to spatially map the donor and acceptor domains
in a model all-polymer bulk heterojunction with resolution approaching 10 nm.
Domain size from PiFM images is compared to bulk-averaged results from resonant
soft X-ray scattering, indicating excellent quantitative agreement. Further, we
demonstrate that in our all-polymer system, the AFM topography, AFM phase, and
PiFM show poor correlation, highlighting the need to move beyond standard AFM for
morphology characterization of bulk heterojunctions.
PMID- 29338203
TI - Boron Analogue of Vinylidene Dication Supported by Phosphines.
AB - In the presence of a catalytic amount of heavier tetrylene dichlorides, an
allenic diborene 1 undergoes a 1,3-hydrogen shift to afford a terminal diborene
2, which can be deemed a boron analogue of vinylidene dication stabilized by
Lewis bases. X-ray diffraction analysis and computational studies revealed that 2
involves a conjugative interaction between the C?C and B?B pi-orbitals. The
reaction of 2 with ZnBr2 afforded the corresponding isolable complex 3, in which
two boon centers coordinate to the Zn atom asymmetrically.
PMID- 29338204
TI - Correction to Hydrogen Sulfide Capture: From Absorption in Polar Liquids to
Oxide, Zeolite, and Metal-Organic Framework Adsorbents and Membranes.
PMID- 29338205
TI - Control of Amphiphile Self-Assembly via Bioinspired Metal Ion Coordination.
AB - Inspired by marine siderophores that exhibit a morphological shift upon metal
coordination, hybrid peptide-polymer conjugates that assemble into different
morphologies based on the nature of the metal ion coordination have been
designed. Coupling of a peptide chelator, hexahistidine, with hydrophobic
oligostyrene allows a modular strategy to be established for the efficient
synthesis and purification of these tunable amphiphiles (oSt(His)6). Remarkably,
in the presence of different divalent transition metal ions (Mn, Co, Ni, Cu, Zn,
and Cd) a variety of morphologies were observed. Zinc(II), cobalt(II), and
copper(II) led to aggregated micelles. Nickel(II) and cadmium(II) produced
micelles, and multilamellar vesicles were obtained in the presence of
manganese(II). This work highlights the significant potential for transition
metal ion coordination as a tool for directing the assembly of synthetic
nanomaterials.
PMID- 29338206
TI - Application of Proton-Transfer-Reaction Mass Spectrometry (PTR-MS) and 33S
Isotope Labeling for Monitoring Sulfur Processes in Livestock Waste.
AB - Reduced sulfur compounds emitted from livestock production cause odor nuisance
for local residents. The microbial processes responsible for this are not well
described in swine manure and a method for monitoring the biological processes is
necessary to develop strategic abatement technologies. In this study, Proton
Transfer-Reaction Mass Spectrometry and isotope-labeled sulfate were combined and
applied to elucidate the sulfur processes in swine manure with high time
resolution. We successfully monitored reduction of isotope 33S labeled sulfate
into corresponding 33S hydrogen sulfide and found that some of the 33S hydrogen
sulfide was further methylated into 33S methanethiol. The isotope patterns in
reduced sulfur compounds together with usage of inhibitors enabled us to
calculate a sulfate reduction rate of 1.03 +/- 0.18 mM/day equivalent to 76.9 +/-
3.0% of total hydrogen sulfide emissions. Cysteine degradation constituted 20.2
+/- 2.7% of the total hydrogen sulfide produced and the remaining hydrogen
sulfide came from demethylation of methanethiol and dimethyl sulfide. Another
source to methanethiol, besides hydrogen sulfide methylation, was methionine
degradation, which contributed with 78.3 +/- 2.5% of the methanethiol production,
whereas the remaining 21.7 +/- 2.5% came from hydrogen sulfide methylation. This
study suggests, therefore, that emissions of odorous sulfur compounds from swine
manure can be reduced by inhibiting methionine degradation and sulfate reduction.
PMID- 29338207
TI - Total Synthesis of (-)-Xylogranatopyridine B via a Palladium-Catalyzed Oxidative
Stannylation of Enones.
AB - We report a total synthesis of the pyridine-containing limonoid alkaloid (-)
xylogranatopyridine B in 11 steps from commercially available dihydrocarvone. The
central pyridine ring was assembled by a late-stage fragment coupling approach
employing a modified Liebeskind pyridine synthesis. One fragment was prepared by
an allyl-palladium catalyzed oxidative enone beta-stannylation, in which the key
bimetallic beta-stannyl palladium enolate intermediate undergoes a beta-hydride
elimination. This methodology also allowed introduction of alkyl and silyl groups
to the beta-position of enones.
PMID- 29338208
TI - Hierarchical Composite Membranes with Robust Omniphobic Surface Using Layer-By
Layer Assembly Technique.
AB - In this study, composite membranes were fabricated via layer-by-layer (LBL)
assembly of negatively charged silica aerogel (SiA) and 1H,1H,2H,2H
perfluorodecyltriethoxysilane (FTCS) on a polyvinylidene fluoride phase inversion
membrane and interconnecting them with positively charged
poly(diallyldimethylammonium chloride) (PDDA) via electrostatic interaction. The
results showed that the PDDA-SiA-FTCS coated membrane had significantly enhanced
the membrane structure and properties. New trifluoromethyl and
tetrafluoroethylene bonds appeared at the surface of the coated membrane, which
led to lower surface free energy of the composite membrane. Additionally, the LBL
membrane showed increased surface roughness. The improved structure and property
gave the LBL membrane an omniphobic property, as indicated by its good wetting
resistance. The membrane performed a stable air gap membrane distillation (AGMD)
flux of 11.22 L/m2 h with very high salt rejection using reverse osmosis brine
from coal seam gas produced water as feed with the addition of up to 0.5 mM SDS
solution. This performance was much better compared to those of the neat
membrane. The present study suggests that the enhanced membrane properties with
good omniphobicity via LBL assembly make the porous membranes suitable for long
term AGMD operation with stable permeation flux when treating challenging saline
wastewater containing low surface tension organic contaminants.
PMID- 29338209
TI - Injectable Self-Healing Zwitterionic Hydrogels Based on Dynamic Benzoxaborole
Sugar Interactions with Tunable Mechanical Properties.
AB - Dynamic hydrogels based on arylboronic esters have been considered as ideal
platforms for biomedical applications given their self-healing and injectable
characteristics. However, there still exist some critical issues that need to be
addressed or improved, including hydrogel biocompatibility, physiological
usability, and tunability of mechanical properties. Here, two kinds of
phospholipid bioinspired MPC copolymers, one is zwitterionic copolymer (PMB)
containing a fixed 15 mol % of benzoxaborole (pKa ~ 7.2) groups and the other is
zwitterionic glycopolymers (PMG) with varied ratios of sugar groups (20%, 50%,
80%), were synthesized respectively via one-pot facile reversible addition
fragmentation chain transfer (RAFT) polymerization. PMBG hydrogels were formed
spontaneously after mixing 10 wt % of PMB and PMG copolymer solutions because of
dynamic benzoxaborole-sugar interactions. The mechanical properties of nine
hydrogels (3 * 3) with different sugar contents and pHs (7.4, 8.4, 9.4) were
carefully studied by rheological measurements, and hydrogels with higher sugar
content and higher pH were found to have higher strength. Moreover, similar to
other arylboronic ester-based hydrogels, PMBG hydrogels possessed not only self
healing and injectable properties but also pH/sugar responsiveness. Additionally,
in vitro cytotoxicity tests of gel extracts on both normal and cancer cells
further confirmed the excellent biocompatibility of the hydrogels, which should
be ascribed to the biomimetic nature of phosphorylcholine (PC) and sugar residues
of the copolymers. Consequently, the zwitterionic dynamic hydrogels provide
promising future for diverse biomedical applications.
PMID- 29338210
TI - An Emission-Free Vacuum Chlorinating Process for Simultaneous Sulfur Fixation and
Lead Recovery from Spent Lead-Acid Batteries.
AB - Spent lead-acid battery recycling by using conventional technologies is usually
accompanied by releases of lead-containing wastewater as well as emissions of
sulfur oxides and lead particulates that may potentially cause secondary
pollution. This study developed a vacuum chlorinating process for simultaneous
sulfur fixation and high-purity lead chloride (PbCl2) recovery from spent lead
paste by using calcium chloride (CaCl2) and silicon dioxide (SiO2) as reagents.
The process train includes pretreatment, simultaneous PbCl2 production and sulfur
fixation, and PbCl2 volatilization. The pretreatment eliminated chlorine emission
from direct chlorinating reaction of PbO2 in the initial S-paste
(PbSO4/PbO2/PbO/Pb). During the subsequent PbCl2 production and sulfur fixation
step, lead compounds in the P-paste (PbSO4/PbO) was converted to volatile PbCl2,
and sulfur was simultaneously fixed to the solid residues in the form of CaSO4 to
eliminate the emission of sulfur oxides. The final step, PbCl2 volatilization
under vacuum, is a physical phase-transformation process of ionic crystals,
following a zeroth-order kinetic model. A cost estimate indicates a profit of USD
$ 8.50/kg PbCl2. This process offers a novel green lead recovery alternative for
spent lead-acid batteries with environmental and economic benefits.
PMID- 29338211
TI - Highly Stable RNA Capture by Dense Cationic Polymer Brushes for the Design of
Cytocompatible, Serum-Stable SiRNA Delivery Vectors.
AB - The high density of polymer brushes confers to these coatings unique
physicochemical properties, in particular for the regulation of biomolecular
interaction and the design of highly selective coatings for biosensors and
protein patterning. Here, we show that high density poly(dimethylaminoethyl
methacrylate) cationic polymer brushes enable the stable uptake of high levels of
oligonucleotides. This is proposed to result from the high degree of crowding and
associated increase in entropic driving force for the binding of polyelectrolytes
such as nucleic acid molecules. We further demonstrate the ease with which such
coatings allow the design of highly structured nanomaterials for siRNA delivery
using block copolymer-brush-based nanoparticles that allow the protection of
oligonucleotides by a protein-resistant outer block. In particular, these
nanomaterials display a high serum stability and low cytotoxicity while retaining
excellent knock down efficiencies. Polymer brush-based nanomaterials therefore
appear particularly attractive for the rational design of a new generation of
high performance theranostics and RNA delivery probes.
PMID- 29338212
TI - Catalytic Dehydrogenative Stannylation of C(sp)-H Bonds Involving Cooperative Sn
H Bond Activation of Hydrostannanes.
AB - The catalytic generation of a stannylium-ion-like tin electrophile by heterolytic
cleavage of the Sn-H bond in hydrostannanes at the Ru-S bond of Ohki-Tatsumi
complexes is reported. Reacting these activated hydrostannanes with terminal
acetylenes does not lead to hydrostannylation of the C-C triple bond but to
dehydrogenative stannylation of the alkyne terminus. The scope of this rare
direct C(sp)-H bond stannylation with hydrostannanes is broad, and a mechanism
involving a beta-tin-stabilized vinyl cation likely having a bridged structure is
presented.
PMID- 29338213
TI - Selective Dehydrogenative Coupling of Ethylene to Butadiene via an
Iridacyclopentane Complex.
AB - An iridium complex is found to catalyze the selective dehydrogenative coupling of
ethylene to 1,3-butadiene. The key intermediate, and a major resting state, is an
iridacyclopentane that undergoes a surprisingly facile beta-H elimination,
enabled by a partial dechelation (kappa3-kappa2) of the supporting 3,5
dimethylphenyl-2,6-bis(oxazolinyl) ligand.
PMID- 29338215
TI - Improving Flue Gas Mercury Removal in Waste Incinerators by Optimization of
Carbon Injection Rate.
AB - This study tested the mercury emission characteristics of six municipal solid
waste incinerators (MSWIs) and recommended future mercury control via adjusting
operational parameters. The results indicated that over 99% of the mercury in
solid wastes ended in fly ash and flue gas, of which 3.3-66.3% was emitted to air
through stack gas. Mercury in the stack gas was mainly in the form of oxidized
mercury (Hg2+), the proportion (65.4-89.0%) of which was far higher than previous
estimation (15%). Mercury removal efficiencies (MRE) of the tested incinerators
were in the range of 33.6-95.2%. The impact of waste incineration capacity, gas
flow, fly ash yield, and activated carbon (AC) injection on MRE were analyzed. We
found that the MRE was significantly linearly correlated to the ratio of AC
injection and fly ash yield (correlation coefficient = 0.98, significance <0.01).
AC injection value is determined based on the control of dioxin emissions without
considering mercury control in traditional design. To increase MRE of MSWIs, the
AC injection should increase from around 100 mg.Nm-3 to 135 mg.Nm-3 for grate
furnace combustor and 170 mg.Nm-3 for circulation fluidized bed combustor, so as
to reach a MRE of 90%.
PMID- 29338214
TI - A Tool for the Import of Natural and Unnatural Nucleoside Triphosphates into
Bacteria.
AB - Nucleoside triphosphates play a central role in biology, but efforts to study
these roles have proven difficult because the levels of triphosphates are tightly
regulated in a cell and because individual triphosphates can be difficult to
label or modify. In addition, many synthetic biology efforts are focused on the
development of unnatural nucleoside triphosphates that perform specific functions
in the cellular environment. In general, both of these efforts would be
facilitated by a general means to directly introduce desired triphosphates into
cells. Previously, we demonstrated that recombinant expression of a nucleoside
triphosphate transporter from Phaeodactylum tricornutum (PtNTT2) in Escherichia
coli functions to import triphosphates that are added to the media. Here, to
explore the generality and utility of this approach, we report a structure
activity relationship study of PtNTT2. Using a conventional competitive uptake
inhibition assay, we characterize the effects of nucleobase, sugar, and
triphosphate modification, and then develop an LC-MS/MS assay to directly measure
the effects of the modifications on import. Lastly, we use the transporter to
import radiolabeled or 2'-fluoro-modified triphosphates and quantify their
incorporation into DNA and RNA. The results demonstrate the general utility of
the PtNTT2-mediated import of natural or modified nucleoside triphosphates for
different molecular or synthetic biology applications.
PMID- 29338216
TI - Effect of Thermochemical Synthetic Conditions on the Structure and Dielectric
Properties of Ga1.9Fe0.1O3 Compounds.
AB - We report on the tunable and controlled dielectric properties of iron (Fe)-doped
gallium oxide (Ga2O3; Ga1.9Fe0.1O3, referred to as GFO) inorganic compounds. The
GFO materials were synthesized using a standard high-temperature, solid-state
chemical reaction method by varying the thermochemical processing conditions,
namely, different calcination and sintering environments. Structural
characterization by X-ray diffraction revealed that GFO compounds crystallize in
the beta-Ga2O3 phase. The Fe doping has induced slight lattice strain in GFO,
which is evident in structural analysis. The effect of the sintering temperature
(Tsint), which was varied in the range of 900-1200 degrees C, is significant, as
revealed by electron microscopy analysis. Tsint influences the grain size and
microstructure evolution, which, in turn, influences the dielectric and
electrical properties of GFO compounds. The energy-dispersive X-ray spectrometry
and mapping data demonstrate the uniform distribution of the elemental
composition over the microstructure. The temperature- and frequency-dependent
dielectric measurements indicate the characteristic features that are
specifically due to Fe doping in Ga2O3. The spreading factor and relaxation time,
calculated using Cole-Cole plots, are in the ranges of 0.65-0.76 and 10-4 s,
respectively. The results demonstrate that densification and control over the
microstructure and properties of GFO can be achieved by optimizing Tsint.
PMID- 29338217
TI - Unprecedented Synergistic Effects of Nanoscale Nutrients on Growth, Productivity
of Sweet Sorghum [Sorghum bicolor (L.) Moench], and Nutrient Biofortification.
AB - Evidence-based synergistic effects of nanoscale materials (size of <100 nm in at
least one dimension) were scantly documented in agriculture at field scale.
Herein, we report for the first time on effects of nanoscale zinc oxide (n-ZnO),
calcium oxide (n-CaO), and magnesium oxide (n-MgO) on growth and productivity of
sweet sorghum [Sorghum bicolor (L.) Moench]. A modified sol-gel method was used
to prepare nanoscale materials under study. Characterization was performed using
transmission and scanning electron microscopies, X-ray diffraction, and dynamic
light scattering. Average sizes (25, 53.7, and 53.5 nm) and zeta potentials (
10.9, -28.2, and -16.2 mV) of n-ZnO, n-CaO, and n-MgO were measured,
respectively. The significant grain yield (17.8 and 14.2%), cane yield (7.2 and
8.0%), juice yield (10 and 12%), and higher sucrose yield (21.8 and 20.9%) were
recorded with the application of nanoscale materials in the years 2014 and 2015,
respectively. Nutrient uptake was significant with foliar application of
nanoscale nutrients.
PMID- 29338218
TI - Mimicking the Key Functions of Photosystem II in Artificial Photosynthesis for
Photoelectrocatalytic Water Splitting.
AB - It has been anticipated that learning from nature photosynthesis is a rational
and effective way to develop artificial photosynthesis system, but it is still a
great challenge. Here, we assembled a photoelectrocatalytic system by mimicking
the functions of photosystem II (PSII) with BiVO4 semiconductor as a light
harvester protected by a layered double hydroxide (NiFeLDH) as a hole storage
layer, a partially oxidized graphene (pGO) as biomimetic tyrosine for charge
transfer, and molecular Co cubane as oxygen evolution complex. The integrated
system exhibited an unprecedentedly low onset potential (0.17 V) and a high
photocurrent (4.45 mA cm-2), with a 2.0% solar to hydrogen efficiency.
Spectroscopic studies revealed that this photoelectrocatalytic system exhibited
superiority in charge separation and transfer by benefiting from mimicking the
key functions of PSII. The success of the biomimetic strategy opened up new ways
for the rational design and assembly of artificial photosynthesis systems for
efficient solar-to-fuel conversion.
PMID- 29338219
TI - Pretargeted Immuno-PET Based on Bioorthogonal Chemistry for Imaging EGFR Positive
Colorectal Cancer.
AB - Pretargeted immuno-PET imaging based on the bioorthogonal chemistry between 18F
labeled Reppe anhydride derivatives and tetrazine conjugates of the EGFR-specific
monoclonal antibodies cetuximab and panitumumab was performed. This pretargeting
approach yielded high target-to-nontarget ratios. Furthermore, due to the fast
clearance rate of the PET probe, the overall radiation burden to nontarget
tissues was also substantially decreased.
PMID- 29338220
TI - The Multiple Role of Bromide Ion in PPCPs Degradation under UV/Chlorine
Treatment.
AB - This study investigated the role of bromide ions in the degradation of nine
pharmaceuticals and personal care products (PPCPs) during the UV/chlorine
treatment of simulated drinking water containing 2.5 mgC L-1 natural organic
matter (NOM). The kinetics of contributions from UV irradiation and from
oxidation by free chlorine, free bromine, hydroxyl radical and reactive halogen
species were evaluated. The observed loss rate constants of PPCPs in the presence
of 10 MUM bromide were 1.6-23 times of those observed in the absence of bromide
(except for iopromide and ibuprofen). Bromide was shown to play multiple roles in
PPCP degradation. It reacts rapidly with free chlorine to produce a trace amount
of free bromine, which then contributes to up to 55% of the degradation of some
PPCPs during 15 min of UV/chlorine treatment. Bromide was also shown to reduce
the level of HO* and to change the reactive chlorine species to bromine
containing species, which resulted in decreases in ibuprofen degradation and
enhancement in carbamazepine and caffeine degradation, respectively. Reactive
halogen species contributed to between 37 and 96% of the degradation of the
studied PPCPs except ibuprofen in the presence of 10 MUM bromide ion. The effect
of bromide is non-negligible during the UV/chlorine treatment.
PMID- 29338221
TI - Synthetic Strategy toward the Pentacyclic Core of Melodinus Alkaloids.
AB - The three-component Povarov reaction is efficiently utilized for construction of
the pentacyclic framework of complex Melodinus alkaloids, which is amenable to
expansion to other complex natural products. The key steps were Povarov reaction,
one-pot reductive cyclization, and ring-closing metathesis (RCM) reaction.
PMID- 29338222
TI - Computational Modeling of a Caged Methyl Cation: Structure, Energetics, and
Vibrational Analysis.
AB - DFT calculations for CH3+ within a constrained cage of water molecules permit the
controlled manipulation of distances rax and req to "axial" and "equatorial"
waters. Equatorial CH...O interactions catalyze methyl transfer (MT) between
axial waters. Variation in rax has a greater effect on CH bond lengths and
stretching force constants in the symmetric SN2-like transition structures than
variation in req. In-plane bending frequencies are insensitive to these
variations in cage dimensions, but axial interactions loosen the out-of-plane
bending mode (OP) whereas equatorial interactions stiffen it. Frequencies for
rotational and translational motions of CH3+ within the cage are influenced by
rax and req. In particular, translation of CH3+ in the axial direction is always
coupled to cage motion. With longer rax, CH3+ translation is coupled with
asymmetric CO bond stretching, but with shorter rax, it is also coupled with OP
(equivalent to the umbrella mode of trigonal bipyramidal O...CH3+...O); the
magnitude of the imaginary MT frequency increases steeply as rax diminishes. This
coupling between CH3+ and its cage is removed by eliminating the rows and columns
associated with cage atoms from the full Hessian to obtain a reduced Hessian for
CH3+ alone. Within a certain range of cage dimensions, the reduced Hessian yields
a real frequency for MT. The importance of using a Hessian large enough to
describe the reaction coordinate mode correctly is emphasized for modeling
chemical reactions and particularly for kinetic isotope effects in enzymic MT.
PMID- 29338223
TI - Chemo-enzymatic Synthesis of Clickable Xylo-oligosaccharide Monomers from
Hardwood 4-O-Methylglucuronoxylan.
AB - A chemo-enzymatic pathway was developed to transform 4-O-methylglucuronic acid
(MeGlcpA) containing xylo-oligosaccharides from beechwood into clickable monomers
capable of polymerizing at room temperature and in aqueous conditions to form
unique polytriazoles. While the gluco-oligosaccharide oxidase (GOOX) from
Sarocladium strictum was used to oxidize C6-propargylated oligosaccharides, the
acid-amine coupling reagents 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide
(EDAC) and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride
(DMT-MM) were employed and compared for their ability to append click
functionalities to carboxylic acid groups of enzyme-treated oligosaccharides.
While DMT-MM was a superior coupling reagent for this application, a triazine
side product was observed during C-1 amidation. Resulting bifunctional xylo
oligosaccharide monomers were polymerized using a Cu(I) catalyst, forming a soft
gel which was characterized by 1H NMR, confirming the triazole product.
PMID- 29338224
TI - Deviation from the trans-Effect in Ligand-Exchange Reactions of Zeise's Ions
PtCl3(C2H4)- with Heavier Halides (Br-, I-).
AB - Four new Zeise's family ions with mixed-halide ligands, i.e., PtClnX3-n(C2H4)- (X
= Br, I; n = 1, 2), were synthesized via ligand-exchange reactions of KX salts
with KPtCl3(C2H4) in aqueous solutions, and were detected in vacuum via
electrospray ionization mass spectrometry. Their photoelectron spectra reveal a
series of well-resolved spectral peaks with their electron binding energies
(EBEs) decreasing with increasing halide size, with I having a much stronger
effect than Br, i.e., 4.57 (-Cl3) > 4.56 (-Cl2Br) > 4.53 (-ClBr2) > 4.34 (-Cl2I)
> 4.30 eV (-ClI2). Ab initio electronic structure calculations including spin
orbit coupling (SOC) predict that the cis- and trans-isomers are nearly
isoenergetic with the cis-isomer for -Cl2X and the trans-isomer for -ClX2
slightly favored, respectively. Excited-state spectra calculated with time
dependent density functional theory (TDDFT), and their comparison with the
observed ones, suggest that for each species both the cis- and trans
configurations coexist in the experiments and contribute to the observed spectra,
a fact that clearly deviates from the prediction of the widely accepted trans
effect, which suggests that only one isomer would have formed.
PMID- 29338225
TI - Stereoselective Photodimerization of 3-Arylindenones in Solution and in the Solid
State.
AB - Photodimerization of 3-arylindenones in solution and in the solid state was
examined. Irradiation of 3-arylindenones in benzene exclusively gave C2-symmetric
anti-HH cyclobutane dimers in good yields. In contrast, photolysis in the solid
state afforded syn-HH cyclobutane dimers efficiently, which was considerably
influenced by the molecular arrangement in the crystal lattice.
PMID- 29338226
TI - Prenylated 2-Phenoxychromones and Flavonoids from Epimedium brevicornum and
Revised Structures of Epimedonins A and B.
AB - Six hitherto unknown prenylated 2-phenoxychromones, epimedonin G (1), 7-O
methylepimedonin G (2), and epimedonins H-K (3-6), and two new prenylflavonoids,
epimedonin L (7) and 3"-O-desmethylspinorhamnoside (8), were isolated from an
ethanol extract of the aerial parts of Epimedium brevicornum. Their structures
were established on the basis of spectroscopic data interpretation. Compound 7
exhibited cytotoxic activity when evaluated against four human cancer cell lines
(HL-60, A-549, MCF-7, and SW-480), with IC50 values of <10 MUM. In addition, the
structures of epimedonins A and B (9a, 10a), recently isolated from E. koreanum,
were corrected by reanalysis of the published NMR data.
PMID- 29338227
TI - Entangled Photonic-Nuclear Molecular Dynamics of LiF in Quantum Optical Cavities.
AB - The quantum photodynamics of a simple diatomic molecule with a permanent dipole
immersed within an optical cavity containing a quantized radiation field is
studied in detail. The chosen molecule under study, lithium fluoride (LiF), is
characterized by the presence of an avoided crossing between the two lowest
1Sigma potential energy curves (covalent-ionic diabatic crossing). Without field,
after prompt excitation from the ground state 1 1Sigma, the excited nuclear wave
packet moves back and forth in the upper 2 1Sigma state, but in the proximity of
the avoided crossing, the nonadiabatic coupling transfers part of the nuclear
wave packet to the lower 1 1Sigma state, which eventually leads to dissociation.
The quantized field of a cavity also induces an additional light crossing in the
modified dressed potential energy curves with similar transfer properties. To
understand the entangled photonic-nuclear dynamics, we solve the time-dependent
Schrodinger equation by using the multiconfigurational time-dependent Hartree
method (MCTDH). The single mode quantized field of the cavity is represented in
the coordinate space instead of in the Fock space, which allows us to deal with
the field as an additional vibrational mode within the MCTDH procedure on equal
footing. We prepare the cavity with different quantum states of light, namely,
Fock states, coherent states, and squeezed coherent states. Our results reveal
pure quantum light effects on the molecular photodynamics and the dissociation
yields of LiF, which are quite different from the light-undressed case and which
cannot be described in general by a semiclassical approach using classical
electromagnetic fields.
PMID- 29338228
TI - Total Synthesis and Structural Determination of XR774, a Tyrosine Kinase
Inhibitor.
AB - Total synthesis and structural determination of XR774 has been accomplished. The
benzo[ j]fluoranthene skeleton has been constructed by regioselective coupling
between tetraline 3 and tetralone 4 successively followed by the sequential
transformation including the Birch reduction to prepare allylic alcohol,
simultaneous bromination of vinylic and aromatic moieties, and the nickel
mediated intramolecular coupling reaction. The optical resolution of racemic 17
led to the first total synthesis of (-)-XR774.
PMID- 29338229
TI - Reconstitution of Kinamycin Biosynthesis within the Heterologous Host
Streptomyces albus J1074.
AB - Diazofluorene compounds such as kinamycin and lomaiviticin feature unique
molecular structures and compelling medicinal bioactivities. However, a complete
understanding of the biosynthetic details for this family of natural products has
yet to be fully elucidated. In addition, a lack of genetically and technically
amenable production hosts has limited access to the full medicinal potential of
these compounds. Here, we report the capture of the complete kinamycin gene
cluster from Streptomyces galtieri Sgt26 by bacterial artificial chromosome
cloning, confirmed by successful production of kinamycin in the heterologous host
Streptomyces albus J1074. Sequence analysis and a series of gene deletion
experiments revealed the boundary of the cluster, which spans 75 kb DNA. To probe
the last step in biosynthesis, acetylation of kinamcyin F to kinamycin D, gene
knockout, and complementation experiments identified a single gene product
involved with final acetylation conversions. This study provides full genetic
information for the kinamycin gene cluster from S. galtieri Sgt26 and establishes
heterologous biosynthesis as a production platform for continued mechanistic
assessment of compound formation and utilization.
PMID- 29338230
TI - Organosilicon Reducing Reagents for Stereoselective Formations of Silyl Enol
Ethers from alpha-Halo Carbonyl Compounds.
AB - Salt-free stereoselective synthesis of silyl enol ethers was achieved by treating
alpha-halo carbonyl compounds with 2,3,5,6-tetramethyl-1,4-bis(trimethylsilyl)
1,4-dihydropyrazine. In this reaction, easily removable trimethylsilyl halides
and 2,3,5,6-tetramethylpyrazine were generated as the reaction byproducts. Due to
the inertness of the reaction byproducts, we found a one-pot transformation of
the in situ generated silyl enol ethers into various alpha-functionalized
carbonyls by reaction with Togni-II reagent or aldehydes.
PMID- 29338231
TI - Fluorous-Phase Approach to alpha-Hydroxytropolone Synthesis.
AB - alpha-Hydroxytropolones (alphaHTs) are troponoids that demonstrate inhibition
against an array of therapeutically significant targets, making them potential
drug leads for several human diseases. We have utilized a recently discovered one
pot three-component oxidopyrylium cycloaddition in a solid-supported synthesis of
alphaHTs. Though the procedure is time efficient and generates assay-ready
molecules, the system suffers from low yields and an inability to perform
reaction modifications on resin-bound intermediates. In order to combat these
issues with the solid-phase platform, we incorporated fluorous tags into our
synthetic route. Through the implementation of fluorous phase chemistry, we
demonstrate a substantial increase in the overall yield of alphaHTs, as well as
an ability to execute metal-catalyzed cross coupling and amide coupling on
fluorous tagged intermediates. We also show that tagged molecules can be
separated from nonfluorous impurities, and vice versa, by utilizing fluorous
liquid-liquid and solid-phase extractions. Hence, these proof-of-principle
investigations describe the viability of a fluorous phase approach to alphaHT
synthesis and its potential to serve as a combinatorial technique to produce
structurally diverse substrates.
PMID- 29338232
TI - Improved Descriptors for the Quantitative Structure-Activity Relationship
Modeling of Peptides and Proteins.
AB - The ability to model the activity of a protein using quantitative structure
activity relationships (QSAR) requires descriptors for the 20 naturally coded
amino acids. In this work we show that by modifying some established descriptors
we were able to model the activity data of 140 mutants of the enzyme epoxide
hydrolase with improved accuracy. These new descriptors (referred to as physical
descriptors) also gave very good results when tested against a series of four
dipeptide data sets. The physical descriptors encode the amino acids using only
two orthogonal scales: the first is strongly linked to
hydrophilicity/hydrophobicity, and the second, to the volume of the amino acid
residue. The use of these new amino acid descriptors should result in simpler and
more readily interpretable models for the enzyme activity (and potentially other
functions of interest, e.g., secondary and tertiary structure) of peptides and
proteins.
PMID- 29338233
TI - Evaluation of the Giant Ferromagnetic pi-d Interaction in Iron-Phthalocyanine
Molecule.
AB - The interaction between itinerant pi and localized d electrons in metal
phthalocyanines, namely, Jpid interaction, is considered as responsible for the
giant negative magnetoresistance observed in several phthalocyanine-based
conductors, among many other important physical properties. Despite the
fundamental and technological importance of this on-site intramolecular
interaction, its giant ferromagnetic nature has been only recently demonstrated
by the experiments conducted by Murakawa et al. in the neutral radical
[Fe(Pc)(CN)2].2CHCl3 ( Phys. Rev. B 2015 , 92 , 054429 ). In this article, we
present the theoretical evaluation of this interaction combining wave function
based electronic calculations on isolated Fe(Pc)(CN)2 molecules and density
functional theory-based periodic calculations on the crystal. Our calculations
confirm the ferromagnetic nature of the pi-d interaction, with a coupling
constant as large as Jpid/kB = 570 K, in excellent agreement with the
experiments, and the presence of intermolecular antiferromagnetic interactions
driven by the pi-pi overlap of neighboring phthalocyaninato molecules. The
analysis of the wave function of the ground state of the Fe(Pc)(CN)2 molecule
provides the clues of the origin of this giant ferromagnetic pi-d interaction.
PMID- 29338234
TI - Role of Reaction Conditions in the Global and Local Two Parabolas Charge Transfer
Model.
AB - The local and global charge transfer approach based on the two parabolas model is
applied to several problems aiming to show the importance of incorporating the
reaction conditions to evaluate the global and local chemical descriptors. It is
shown that, by preparation of the reactants, the chemical potentials of the
reacting species determined by the two parabolas model satisfy the condition for
the transfer of electrons in the direction dictated by the chemical potential
difference. The model is applied to the hydration of alkenes, showing that it
recovers Markovnikov's rule, to aromatic nitration, and to the interaction of
nitrobenzenes with 1,3-diethylurea, an electrochemically controlled hydrogen
bonding problem. The applications presented show that to satisfy the charge
transfer directionality established by the chemical potential differences
obtained from the two parabolas model, one has to incorporate the reaction
conditions in the evaluation of the global and local chemical descriptors. The
global and local charge transfer predicted along these lines allows one to
determine the direction of electron transfer prevailing in the reaction and also
the most relevant atoms participating in the interactions between the reactants,
aiding in the unraveling of the chemical interactions present in the system under
investigation.
PMID- 29338235
TI - Enantioselective Dearomatization of Alkylpyridiniums by N-Heterocyclic Carbene
Catalyzed Nucleophilic Acylation.
AB - A chiral NHC-catalyzed dearomatizing reaction of activated N-alkylpyridinium
salts with aliphatic aldehydes is described. The resulting acylated 1,4
dihydropyridines have been obtained with complete C4 regioselectivity and
enantioselectivities in the range 52-78% ee. The (4R)-absolute configuration of
the synthesized compounds has been determined by the TD-DFT simulation of the
electronic circular dichroism spectra.
PMID- 29338236
TI - Detection of the Cytotoxic Penitrems A-F in Cheese from the European Single
Market by HPLC-MS/MS.
AB - Penitrems are fungal indole diterpene-derived tremorgenic secondary metabolites,
which are mainly produced by Penicillium spp. Several cases of intoxications with
penitrems and subsequent occurrences of penitrem A in foodstuff underline the
need for reliable quantitation methods for the detection of these mycotoxins in
food. In this study, a simple and fast high-performance liquid chromatography
tandem mass spectrometry (HPLC-MS/MS) method for the quantitative analysis of
penitrems A-F in cheese was developed. Therefore, penitrems A-F were isolated
from Penicillium crustosum as analytical reference standards. The analysis of 60
cheese samples from the European single market (EU) revealed the occurrence of
penitrem A in 10% of the analyzed samples with an average concentration of 28.4
MUg/kg and a maximum concentration of 429 MUg/kg. In addition to penitrem A,
other members of the group of penitrems, namely, penitrems B, C, D, E, and F,
were for the first time quantitatively detected in food samples, although in
lower concentrations and with lower incidence in comparison to penitrem A.
Moreover, we report cytotoxic effects of all penitrems on two cell lines (HepG2
and CCF-STTG1). This clearly underlines their relevance and the importance to
analyze food samples in order to get insights into the human exposure toward
these mycotoxins.
PMID- 29338237
TI - Reactivity of Metal Carbenes with Olefins: Theoretical Insights on the Carbene
Electronic Structure and Cyclopropanation Reaction Mechanism.
AB - Present work addresses the reactivity of several phenyl-substituted metal-carbene
complexes with 4-methylstyrene by means of density functional theory OPBE
simulations. Different paths that lead to cyclopropanation were explored and
compared to the olefin metathesis mechanism. For this purpose, we chose four
different catalysts: (i) the Grubbs second-generation olefin metathesis catalyst,
(ii) a Grubs second-generation-like complex, in which ruthenium is replaced by
iron, and (iii) two iron carbene complexes (a piano stool and a porphyrin iron
carbene) that experimentally catalyze alkene cyclopropanation. Results suggest
that the nature of the applying mechanism is very sensitive to the coordination
around the metal center and the spin state of the metal-carbene complex.
Cyclopropanation by open-shell metal-carbene complexes seems to preferentially
proceed through a two-step radical mechanism, in which the two C-C bonds are
sequentially formed (path C). Singlet-state carbenes proceed either through a
direct attack of the olefin to the carbene (path D) when the formation of the
metallacycle is not feasible or through a reductive elimination from the
metallacyclobutane when this intermediate is accessible both kinetically and
thermodynamically (path B).
PMID- 29338238
TI - Paralithocins, Antimicrobial Peptides with Unusual Disulfide Connectivity from
the Red King Crab, Paralithodes camtschaticus.
AB - As part of an ongoing exploration of marine invertebrates as a source of new
antimicrobial peptides, hemocyte extracts from the red king crab, Paralithodes
camtschaticus, were studied. Three cationic cysteine (Cys)-rich peptides, named
paralithocins 1-3, were isolated by bioassay-guided purification, and their amino
acid sequences determined by Edman degradation and expressed sequences tag
analysis. Disulfide bond mapping was performed by high-resolution tandem mass
spectrometry. The peptides (38-51 amino acids in length) share a unique Cys motif
composed of eight Cys, forming four disulfide bridges with a bond connectivity of
(Cys relative position) Cys1-Cys8, Cys2-Cys6, Cys3-Cys5, and Cys4-Cys7, a
disulfide arrangement that has not been previously reported among antimicrobial
peptides. Thus, paralithocins 1-3 may be assigned to a previously unknown family
of antimicrobial peptides within the group of Cys-rich antimicrobial peptides.
Although none of the isolated peptides displayed antimicrobial activity against
the target strains Escherichia coli, Pseudomonas aeruginosa, or Staphylococcus
aureus, they inhibited the growth of several marine bacterial strains with
minimal inhibitory concentrations in the 12.5-100 MUM range. These findings
corroborate the hypothesis that marine organisms are a valuable source for
discovering bioactive peptides with new structural motifs.
PMID- 29338239
TI - Vinyl Grignard-Mediated Stereoselective Carbocyclization of Lactone Acetals.
AB - A novel Ferrier-type carbocyclization is reported. It involves a carbohydrate
derived lactone acetal synthesized from methyl alpha-d-glucopyranoside, which
upon treatment with excess vinylmagnesium bromide provides a highly substituted
carbocyclic product as a single stereoisomer. The yield is greatly increased when
N,N,N',N'-tetramethylethylenediamine is added to the reaction mixture. Optimized
reaction conditions have been applied to lactone acetals derived from other
carbohydrates. Based on the obtained results, a possible reaction mechanism has
been proposed. Furthermore, scalability of the reaction up to 15 g scale and
derivatization of the carbocyclic product has been demonstrated, including the
formation of a rare trans-bicyclo[4.3.0]nonene scaffold via a ring-closing
metathesis. The structure of this and all carbocyclic products were confirmed by
X-ray crystallographic analysis.
PMID- 29338240
TI - BiKi Life Sciences: A New Suite for Molecular Dynamics and Related Methods in
Drug Discovery.
AB - In this paper, we introduce the BiKi Life Sciences suite. This software makes it
easy for computational medicinal chemists to run ad hoc molecular dynamics
protocols in a novel and task-oriented environment; as a notebook, BiKi (acronym
of Binding Kinetics) keeps memory of any activity together with dependencies
among them. It offers unique accelerated protein-ligand binding/unbinding methods
and other useful tools to gain actionable knowledge from molecular dynamics
simulations and to simplify the drug discovery process.
PMID- 29338241
TI - Characterization of Macrophage Endogenous S-Nitrosoproteome Using a Cysteine
Specific Phosphonate Adaptable Tag in Combination with TiO2 Chromatography.
AB - Protein S-nitrosylation is a cysteine post-translational modification mediated by
nitric oxide. An increasing number of studies highlight S-nitrosylation as an
important regulator of signaling involved in numerous cellular processes. Despite
the significant progress in the development of redox proteomic methods,
identification and quantification of endogeneous S-nitrosylation using high
throughput mass-spectrometry-based methods is a technical challenge because this
modification is highly labile. To overcome this drawback, most methods induce S
nitrosylation chemically in proteins using nitrosylating compounds before
analysis, with the risk of introducing nonphysiological S-nitrosylation. Here we
present a novel method to efficiently identify endogenous S-nitrosopeptides in
the macrophage total proteome. Our approach is based on the labeling of S
nitrosopeptides reduced by ascorbate with a cysteine specific phosphonate
adaptable tag (CysPAT), followed by titanium dioxide (TiO2) chromatography
enrichment prior to nLC-MS/MS analysis. To test our procedure, we performed a
large-scale analysis of this low-abundant modification in a murine macrophage
cell line. We identified 569 endogeneous S-nitrosylated proteins compared with
795 following exogenous chemically induced S-nitrosylation. Importantly, we
discovered 579 novel S-nitrosylation sites. The large number of identified
endogenous S-nitrosylated peptides allowed the definition of two S-nitrosylation
consensus sites, highlighting protein translation and redox processes as key S
nitrosylation targets in macrophages.
PMID- 29338242
TI - In-Situ Biocatalytic Production of Trehalose with Autoinduction Expression of
Trehalose Synthase.
AB - We developed an in-situ biocatalytic process that couples autoinduction
expression of trehalose synthase (TreS) and whole-cell catalysis for trehalose
production. With lactose as the autoinducer, the activity of recombinant TreS in
recombinant Escherichia coli was optimized through a visualization method, which
resulted in a maximum value of 12 033 +/- 730 U/mL in pH-stat fed-batch
fermentation mode. Meanwhile, the permeability of the autoinduced E. coli
increased significantly, which makes it possible to be directly used as a whole
cell biocatalyst for trehalose production, whereby the byproduct glucose can also
act as an extra carbon source. In this case, the final yield of trehalose was
improved to 90.5 +/- 5.7% and remained as high as 83.2 +/- 5.0% at the 10th
batch, which is the highest value achieved using recombinant TreS. Finally, an
integrated strategy for trehalose production was established, and its advantages
compared to the traditional mode have been summarized.
PMID- 29338243
TI - Metadynamics Enhanced Markov Modeling of Protein Dynamics.
AB - Enhanced sampling techniques represent a versatile approach to account for rare
conformational transitions in biomolecules. A particularly promising strategy is
to combine massive parallel computing of short molecular dynamics (MD)
trajectories (to sample the free energy landscape of the system) with Markov
state modeling (to rebuild the kinetics from the sampled data). To obtain well
distributed initial structures for the short trajectories, it is proposed to
employ metadynamics MD, which quickly sweeps through the entire free energy
landscape of interest. Being only used to generate initial conformations, the
implementation of metadynamics can be simple and fast. The conformational
dynamics of helical peptide Aib9 is adopted to discuss various technical issues
of the approach, including metadynamics settings, minimal number and length of
short MD trajectories, and the validation of the resulting Markov models. Using
metadynamics to launch some thousands of nanosecond trajectories, several Markov
state models are constructed that reveal that previous unbiased MD simulations of
in total 16 MUs length cannot provide correct equilibrium populations or
qualitative features of the pathway distribution of the short peptide.
PMID- 29338244
TI - Synthesis and Reaction of ortho-Benzoquinone Monohemiaminals.
AB - The preparation and reactions of ortho-benzoquinone monohemiaminals are
described. The oxidative dearomatization of phenols bearing amino alcohol groups
induced N-cyclization to afford ortho-benzoquinone monohemiaminals. The N
cyclization stereoselectively affords the product when a chiral amino alcohol is
used as the substituent. The chiral ortho-benzoquinone monohemiaminal undergoes
stereoselective Diels-Alder reactions with electron-deficient alkenes, as
expected, confirming the promising utility of ortho-benzoquinone monohemiaminals.
PMID- 29338245
TI - One-Pot Synthesis of Benzo[b][1,4]oxazins via Intramolecular Trapping Iminoenol.
AB - A highly atom-efficient "one-pot" protocol has been developed to construct
multisubstituted 2-hydroxy-benzo[b][1,4]oxazins starting from N-(2
hydroxylaryl)enaminones. This procedure comprises a PIDA-mediated intramolecular
iminoenol tautomer trapping reaction, followed by Et3N-promoted aerobic oxidative
ring construction. In particular, an O2 molecule from air served as the oxygen
source of the hydroxyl group in the titled products. This reaction proceeded
smoothly at room temperature under air atmosphere and metal-free conditions.
PMID- 29338246
TI - Non-Transition-Metal Catalytic System for N2 Reduction to NH3: A Density
Functional Theory Study of Al-Doped Graphene.
AB - The prevalent catalysts for natural and artificial N2 fixation are known to hinge
upon transition-metal (TM) elements. Herein, we demonstrate by density functional
theory that Al-doped graphene is a potential non-TM catalyst to convert N2 to NH3
in the presence of relatively mild proton/electron sources. In the integrated
structure of the catalyst, the Al atom serves as a binding site and catalytic
center while the graphene framework serves as an electron buffer during the
successive proton/electron additions to N2 and its various downstream NxHy
intermediates. The initial hydrogenation of N2 can readily take place via an
internal H-transfer process with the assistance of a Li+ ion as an additive. In
view of the recurrence of H transfer in the first step of N2 reduction observed
in biological nitrogenases and other synthetic catalysts, this finding highlights
the significance of heteroatom-assisted H transfer in the design of synthetic
catalysts for N2 fixation.
PMID- 29338247
TI - Lattice Models of Bacterial Nucleoids.
AB - Mesoscale molecular modeling is providing a new window into the inner workings of
living cells. Modeling of genomes, however, remains a technical challenge, due to
their large size and complexity. We describe a lattice method for rapid
generation of bacterial nucleoid models that integrates experimental data from a
variety of biophysical techniques and provides a starting point for simulation
and hypothesis generation. The current method builds models of a circular
bacterial genome with supercoiled plectonemes, packed within the small space of
the bacterial cell. Lattice models are generated for Mycoplasma genitalium and
Escherichia coli nucleoids, and used to simulate interaction data. The method is
rapid enough to allow generation of multiple models when analyzing
structure/function relationships, and we demonstrate use of the lattice models in
creation of an all-atom representation of an entire cell.
PMID- 29338248
TI - Catalytic Oligopeptide Synthesis.
AB - Waste-free catalytic assembly of alpha-amino acids is fueled by a multiboron
catalyst that features a characteristic B3NO2 heterocycle, providing a versatile
catalytic protocol wherein functionalized natural alpha-amino acid units are
accommodated and commonly used protecting groups are tolerated. The facile
dehydrative conditions eliminate the use of engineered peptide coupling reagents,
exemplifying a greener catalytic alternative for peptide coupling. The catalysis
is sufficiently robust to enable pentapeptide synthesis, constructing all four
amide bond linkages in a catalytic fashion.
PMID- 29338249
TI - Highly Sensitive and Wearable In2O3 Nanoribbon Transistor Biosensors with
Integrated On-Chip Gate for Glucose Monitoring in Body Fluids.
AB - Nanoribbon- and nanowire-based field-effect transistor (FET) biosensors have
stimulated a lot of interest. However, most FET biosensors were achieved by using
bulky Ag/AgCl electrodes or metal wire gates, which have prevented the biosensors
from becoming truly wearable. Here, we demonstrate highly sensitive and conformal
In2O3 nanoribbon FET biosensors with a fully integrated on-chip gold side gate,
which have been laminated onto various surfaces, such as artificial arms and
watches, and have enabled glucose detection in various body fluids, such as sweat
and saliva. The shadow-mask-fabricated devices show good electrical performance
with gate voltage applied using a gold side gate electrode and through an aqueous
electrolyte. The resulting transistors show mobilities of ~22 cm2 V-1 s-1 in 0.1*
phosphate-buffered saline, a high on-off ratio (105), and good mechanical
robustness. With the electrodes functionalized with glucose oxidase, chitosan,
and single-walled carbon nanotubes, the glucose sensors show a very wide
detection range spanning at least 5 orders of magnitude and a detection limit
down to 10 nM. Therefore, our high-performance In2O3 nanoribbon sensing platform
has great potential to work as indispensable components for wearable healthcare
electronics.
PMID- 29338250
TI - Pickering Emulsion Formation of Paraffin Wax in an Ethanol-Water Mixture
Stabilized by Primary Polymer Particles and Wax Microspheres Thereof.
AB - Stable dispersions of paraffin wax droplets and their nano- and microspheres have
broad applications. Despite intensive efforts, the production of uniform wax
spheres remains a challenge. For their preparation, abundant surfactants and
other additives are commonly used to stabilize the dispersions. These additives
are hardly removable and entrain often adverse consequence in many applications,
particularly in biological and medical applications, where microspheres with
absolutely clean surface are preferred. We report here a novel process to prepare
stable dispersion of wax droplets in a water-ethanol mixture with a narrow size
distribution by simply shaking without any surfactants. The process is featured
by using primary polymer particles (PPs) of poly(dodecene-trihydroxymethylpropane
triacrylate) as a Pickering stabilizer. PPs were prepared by precipitation
polymerization without any surfactant and stabilizer. By rapidly cooling the wax
emulsion, solid wax spheres with good uniformity were obtained. Their size,
between 50 and 480 MUm, was easily adjustable by changing the shaking rate,
number of PPs, and particularly the size of PPs. The morphology of the wax
spheres was examined by SEM, which showed that they were covered by a layer of
PPs. The formation mechanism of the microspheres was also discussed on the basis
of the adsorption energy of PPs on wax spheres, estimated from the corresponding
contact angle of the solvent toward the PPs and the wax. This paper presents a
novel pathway for the preparation of wax microspheres with only polymer particles
without the need for any other additives.
PMID- 29338251
TI - Delivery of Oxytocin to the Brain for the Treatment of Autism Spectrum Disorder
by Nasal Application.
AB - Oxytocin (OXT) is a cyclic nonapeptide, two amino acids of which are cysteine,
forming an intramolecular disulfide bond. OXT is produced in the hypothalamus and
is secreted into the bloodstream from the posterior pituitary. As recent studies
have suggested that OXT is a neurotransmitter exhibiting central effects
important for social deficits, it has drawn much attention as a drug candidate
for the treatment of autism. Although human-stage clinical trials of the nasal
spray of OXT for the treatment of autism have already begun, few studies have
examined the pharmacokinetics and brain distribution of OXT after nasal
application. The aim of this study is to evaluate the disposition, nasal
absorption, and therapeutic potential of OXT after nasal administration. The
pharmacokinetics of OXT after intravenous bolus injection to rats followed a two
compartment model, with a rapid initial half-life of 3 min. The nasal
bioavailability of OXT was approximately 2%. The brain concentration of OXT after
nasal application was much higher than that after intravenous application,
despite much lower concentrations in the plasma. More than 95% of OXT in the
brain was directly transported from the nasal cavity. The in vivo stress-relief
effect by OXT was observed only after intranasal administration. These results
indicate that pharmacologically active OXT was effectively delivered to the brain
after intranasal administration. In conclusion, the nasal cavity is a promising
route for the efficient delivery of OXT to the brain.
PMID- 29338252
TI - Orychophragines A-C, Three Biologically Active Alkaloids from Orychophragmus
violaceus.
AB - Orychophragines A-C (1-3), three new alkaloids with an novel 2-piperazinone-fused
2,4-dioxohexahydro-1,3,5-triazine skeleton, were isolated from the seeds of
Orychophragmus violaceus. Their structures were established on the basis of
spectroscopic analysis and X-ray crystallographic analysis. Orychophragines A (1)
exhibited remarkable cytotoxicity against HepG2, A549, Hela, and HCT-116 cells
with IC50 values of 7.73, 10.79, 11.91, and 9.93 MUM, respectively.
Orychophragines C (3) showed moderate 60Co gamma radiation protection activity in
HUVEC cells. A plausible biosynthetic pathway for 1-3 was proposed.
PMID- 29338253
TI - Correction to Highly Efficient Retention of Polysulfides in "Sea-Urchin"-Like
Carbon Nanotube/Nanopolyhedra Superstructures as Cathode Material for Ultralong
Life Lithium-Sulfur Batteries.
PMID- 29338254
TI - Editorial 2018.
PMID- 29338255
TI - To Be Fibrils or To Be Nanofilms? Oligomers Are Building Blocks for Fibril and
Nanofilm Formation of Fragments of Abeta Peptide.
AB - To identify the key stages in the amyloid fibril formation we studied the
aggregation of amyloidogenic fragments of Abeta peptide, Abeta(16-25), Abeta(31
40), and Abeta(33-42), using the methods of electron microscopy, X-ray analysis,
mass spectrometry, and structural modeling. We have found that fragments Abeta(31
40) and Abeta(33-42) form amyloid fibrils in the shape of bundles and ribbons,
while fragment Abeta(16-25) forms only nanofilms. We are the first who performed
2D reconstruction of amyloid fibrils by the Markham rotation technique on
electron micrographs of negatively stained fragments of Abeta peptide. Combined
analysis of the data allows us to speculate that both the fibrils and the films
are formed via association of ring-shaped oligomers with the external diameter of
about 6 to 7 nm, the internal diameter of 2 to 3 nm, and the height of ~3 nm. We
conclude that such oligomers are the main building blocks in fibrils of any
morphology. The interaction of ring oligomers with each other in different ways
makes it possible to explain their polymorphism. The new mechanism of
polymerization of amyloidogenic proteins and peptides, described here, could
stimulate new approaches in the development of future therapeutics for the
treatment of amyloid-related diseases.
PMID- 29338256
TI - Palladium-Catalyzed Four-Component Cascade Reaction for the Synthesis of Highly
Functionalized Acyclic O,O-Acetals.
AB - A palladium-catalyzed four-component cascade reaction of carbon dioxide, amines,
allenyl ethers, and aryl iodides has been developed for the first time. The novel
reaction allows simultaneous construction of three different new bonds (C-N, C-O,
and C-C) in a single step, affording an efficient method for the synthesis of a
variety of highly functionalized acyclic O,O-acetals. Excellent chemo- and
regioselectivity, wide substrate scope, and good functional group tolerance are
features of the method.
PMID- 29338257
TI - A Dynamic Protein-Protein Coupling between the TonB-Dependent Transporter FhuA
and TonB.
AB - Bacterial outer membrane TonB-dependent transporters function by executing cycles
of binding and unbinding to the inner membrane protein TonB. In the vitamin B12
transporter BtuB and the ferric citrate transporter FecA, substrate binding
increases the periplasmic exposure of the Ton box, an energy-coupling segment.
This increased exposure appears to enhance the affinity of the transporter for
TonB. Here, continuous wave and pulse EPR spectroscopy were used to examine the
state of the Ton box in the Escherichia coli ferrichrome transporter FhuA. In its
apo state, the Ton box of FhuA samples a broad range of positions and multiple
conformational substates. When bound to ferrichrome, the Ton box does not extend
further into the periplasm, although the structural states sampled by the FhuA
Ton box are altered. When bound to a soluble fragment of TonB, the TonB-FhuA
complex remains heterogeneous and dynamic, indicating that TonB does not make
strong, specific contacts with either the FhuA barrel or the core region of the
transporter. This result differs from that seen in the crystal structure of the
TonB-FhuA complex. These data indicate that unlike BtuB and FecA, the periplasmic
exposure of the Ton box in FhuA does not change significantly in the presence of
substrate and that allosteric control of transporter-TonB interactions functions
by a different mechanism than that seen in either BtuB or FecA. Moreover, the
data indicate that models involving a rotation of TonB relative to the
transporter are unlikely to underlie the mechanism that drives TonB-dependent
transport.
PMID- 29338258
TI - Nanoparticle-Cell Interactions: Surface Chemistry Effects on the Cellular Uptake
of Biocompatible Block Copolymer Assemblies.
AB - The development of nanovehicles for intracellular drug delivery is strongly bound
to the understating and control of nanoparticles cellular uptake process, which
in turn is governed by surface chemistry. In this study, we explored the
synthesis, characterization, and cellular uptake of block copolymer assemblies
consisting of a pH-responsive poly[2-(diisopropylamino)ethyl methacrylate] (PDPA)
core stabilized by three different biocompatible hydrophilic shells (a
zwitterionic type poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) layer, a
highly hydrated poly(ethylene oxide) (PEO) layer with stealth effect, and an also
proven nontoxic and nonimmunogenic poly(N-(2-hydroxypropyl)methacrylamide)
(PHPMA) layer). All particles had a spherical core-shell structure. The largest
particles with the thickest hydrophilic stabilizing shell obtained from PMPC40-b
PDPA70 were internalized to a higher level than those smaller in size and
stabilized by PEO or PHPMA and produced from PEO122-b-PDPA43 or PHPMA64-b-PDPA72,
respectively. Such a behavior was confirmed among different cell lines, with
assemblies being internalized to a higher degree in cancer (HeLa) as compared to
healthy (Telo-RF) cells. This fact was mainly attributed to the stronger binding
of PMPC to cell membranes. Therefore, cellular uptake of nanoparticles at the sub
100 nm size range may be chiefly governed by the chemical nature of the
stabilizing layer rather than particles size and/or shell thickness.
PMID- 29338260
TI - Seco-Dendrobine-Type Alkaloids and Bioactive Phenolics from Dendrobium
findlayanum.
AB - Investigation of the 95% EtOH extract of stems of Dendrobium findlayanum afforded
four new seco-dendrobines, findlayines A-D (1-4); two known dendrobines,
dendrobine (5) and 2-hydroxydendrobine (6); and four new phenolic compounds,
dendrofindlaphenols A-C (7, 9, and 10) and 6"-de-O-methyldendrofindlaphenol A
(8). Compounds 1 and 2 are the first seco-dendrobines possessing a seven-membered
lactam moiety, with 3 and 4 derived from the oxidative cleavage of the C-2-C-3
bond of dendrobine. The structures were established using spectroscopic methods
and by comparison with literature data. The absolute configurations of 1-4 were
confirmed via single-crystal X-ray diffraction data. Cytotoxic activity assays
against HL-60, SMMC-7721, A-549, MCF-7, and SW480 human cancer cell lines
revealed IC50 values ranging from 2.3 to 5.3 MUM for compound 7, from 19.4 to
34.4 MUM for 8, and from 49.4 to 96.8 MUg/mL for the EtOAc extract. An assay of
the inhibition of NO production with RAW 264.7 cells indicated that 8 had an IC50
value of 21.4 MUM, and the EtOAc extract, 10.5 MUg/mL. The EtOAc extract
possessed DPPH radical scavenging activity of 69.93% at 100 MUg/mL.
PMID- 29338261
TI - Nature of the Three-Electron Bond.
AB - We analyze the properties of 15 3-electron bonds, which include sigma-3-electron
bonds, such as dihalide radical anions and di-noble gas radical cations, pi-3
electron-bonds as in hydrazine radical cations, and doubly-pi-(3e)-bonded species
such as O2, FeO+, S2, etc. The primary analytical tool is the breathing-orbital
valence-bond (BOVB) method, which enables us to quantify the charge shift
resonance energy (RECS) of the three electrons, and the bond dissociation
energies (De). BOVB is tested reliable against MRCI calculations. Our findings
show that in all 3-electron bonds, none of the VB structures have by themselves
any bonding. In fact, in each VB structure, the three electrons maintain Pauli
repulsion, while the entire bonding energy arises from resonance due to the
charge shift between the two or more constituent VB structures. Hence, 3e-bonds
are charge shift bonds (CSBs). The CSB character is probed by calculating the
Laplacian (L) of the 3e-bond. Thus, much like the CSBs in electron-pair bonds,
such as F2 or the central bond in [1.1.1]propellane, here too L is positive, thus
showing the excess kinetic energy of the shared density due to the Pauli
repulsion in the 3-electron VB structures. The RECS values for 3-electron bonds
are invariably larger than the corresponding bond energies. For the doubly-pi
(3e)-bonded species, RECS is very large, exceeding 100 kcal mol-1. As such, it is
fitting to conclude that sigma- and pi-3-electron-bonds find their natural place
in the CSB family along with two-electron CSBs, with which they share identical
energetic and topological characteristics. Experimental manifestations/tests of
3e-CSBs are proposed.
PMID- 29338262
TI - Roasted Barley Extract Affects Blood Flow in the Rat Tail and Increases Cutaneous
Blood Flow and Skin Temperature in Humans.
AB - Roasted barley extract (RBE, "Mugicha") is a traditional Japanese beverage
reported to improve blood viscosity and affect food functionality. RBE is
suggested to contain 2,5-diketopiperazines, which are the functional component
with neuroprotective and immunostimulatory effects that are produced in food
through roasting. In this study, we investigated the effects of RBE on blood
circulation, both clinically and in rats. At first, we confirmed five 2,5
diketopiperazine derivatives in RBE by LC-MS analysis. Secondarily, we revealed
that RBE affects blood flow in the rat tail and compared the efficacy on rat tail
blood flow among five 2,5-diketopiperazines in RBE. Especially, cyclo(d-Phe-l
Pro) was the most effective in increasing blood flow in the rat tail. We also
researched the mechanism of cyclo(d-Phe-l-Pro) with rat aorta study. As a result,
we confirmed that cyclo(d-Phe-l-Pro) has an effect on vasodilatation through the
release of nitric oxide in the vascular endothelium. Finally, we also confirmed
that RBE affects cutaneous blood flow and increases skin temperature in humans.
PMID- 29338263
TI - Use of a Promiscuous Glycosyltransferase from Bacillus subtilis 168 for the
Enzymatic Synthesis of Novel Protopanaxatriol-Type Ginsenosides.
AB - Ginsenosides are the principal bioactive ingredients of Panax ginseng and possess
diverse notable pharmacological activities. UDP-glycosyltransferase (UGT)
mediated glycosylation of the C6-OH and C20-OH of protopanaxatriol (PPT) is the
prominent biological modification that contributes to the immense structural and
functional diversity of PPT-type ginsenosides. In this study, the glycosylation
of PPT and PPT-type ginsenosides was achieved using a promiscuous
glycosyltransferase (Bs-YjiC) from Bacillus subtilis 168. PPT was selected as the
probe for the in vitro glycodiversification of PPT-type ginsenosides using
diverse UDP-sugars as sugar donors. Structural analysis of the newly
biosynthesized products demonstrated that Bs-YjiC can transfer a glucosyl moiety
to the free C3-OH, C6-OH, and C12-OH of PPT. Five PPT-type ginsenosides were
biosynthesized, including ginsenoside Rh1 and four unnatural ginsenosides. The
present study suggests flexible microbial UGTs play an important role in the
enzymatic synthesis of novel ginsenosides.
PMID- 29338264
TI - Quantum Interference Contribution to the Dipole Moment of Diatomic Molecules.
AB - The interference energy partitioning analysis method developed by our group and
used to study the nature of the chemical bond was extended to partition the
electric dipole moment in quasi-classical and interference contributions. Our
results show that interference participates in charge displacement in polar
molecules, providing, directly or indirectly, a relevant contribution for the
total dipole moment. A linear correlation was found between the interference
contribution of the dipole moment from the bond electron group, MUINT(bond), and
the difference of electronegativity of the atoms which form the bond, DeltaXAB.
This interesting result reinforces the fact that electronegativity is not a
property of an atom alone, but rather a property of the atom in the molecule and
that DeltaXAB can only be associated with that part of the total charge
displacement resulting from the formation of the chemical bond. The partitioning
of the total dipole moment into quasi-classical and interference contributions
provides new insights about the reasons for the failure of the DeltaXAB criterion
in predicting the correct orientation of the dipole moment in several molecules.
The results of the present work also bring additional evidence for the previously
proposed mechanism of formation of polar bonds.
PMID- 29338265
TI - Controlling Polyelectrolyte Adsorption onto Carbon Nanotubes by Tuning Ion-Image
Interactions.
AB - Understanding and controlling polyelectrolyte adsorption onto carbon nanotubes is
a fundamental challenge in nanotechnology. Polyelectrolytes have been shown to
stabilize nanotube suspensions through adsorbing onto the nanotube surface, and
polyelectrolyte-coated nanotubes are emerging as building blocks for complex and
addressable self-assembly. Conventional wisdom suggests that polyelectrolyte
adsorption onto nanotubes is driven by specific chemical or van der Waals
interactions. We develop a simple mean-field model and show that ion-image
attraction significantly effects adsorption onto conducting nanotubes at low salt
concentrations. Our theory suggests a simple strategy to selectively and
reversibly functionalize carbon nanotubes on the basis of their electronic
structures, which in turn modify the ion-image attraction.
PMID- 29338266
TI - All-Solid-State Batteries with Thick Electrode Configurations.
AB - We report the preparation of thick electrode all-solid-state lithium-ion cells in
which a large geometric capacity of 15.7 mAh cm-2 was achieved at room
temperature using a 600 MUm-thick cathode layer. The effect of ionic conductivity
on the discharge performance was then examined using two different materials for
the solid electrolyte. Furthermore, important morphological information regarding
the tortuosity factor was electrochemically extracted from the capacity-current
data. The effect of tortuosity on cell performance was also quantitatively
discussed.
PMID- 29338267
TI - Theory for the Liquid-Liquid Phase Separation in Aqueous Antibody Solutions.
AB - This study presents the theory for liquid-liquid phase separation for systems of
molecules modeling monoclonal antibodies. Individual molecule is depicted as an
assembly of seven hard spheres, organized to mimic the Y-shaped antibody. We
consider the antibody-antibody interactions either through Fab, Fab' (two Fab
fragments may be different), or Fc domain. Interaction between these three
domains of the molecule (hereafter denoted as A, B, and C, respectively) is
modeled by a short-range square-well attraction. To obtain numerical results for
the model under study, we adapt Wertheim's thermodynamic perturbation theory. We
use this model to calculate the liquid-liquid phase separation curve and the
second virial coefficient B2. Various interaction scenarios are examined to see
how the strength of the site-site interactions and their range shape the
coexistence curve. In the asymmetric case, where an attraction between two sites
is favored and the interaction energies for the other sites kept constant,
critical temperature first increases and than strongly decreases. Some more
microscopic information, for example, the probability for the particular two
sites to be connected, has been calculated. Analysis of the experimental liquid
liquid phase diagrams, obtained from literature, is presented. In addition, we
calculate the second virial coefficient under conditions leading to the liquid
liquid phase separation and present this quantity on the graph B2 versus protein
concentration.
PMID- 29338268
TI - Predicting Surface Tensions of Surfactant Solutions from Statistical Mechanics.
AB - The importance of surfactants to various industries necessitates a predictive
understanding of their surface tension and adsorption behavior in terms of
molecular characteristics. Previous models are highly empirical, require fitting
parameters, and have limited applicability at various temperatures. Here, we
provide a surface tension model based on statistical mechanics that (1) is
thermodynamically consistent, (2) provides a higher predictive power, wherein
surface tension can be calculated for any tail length, concentration, and
temperature from molecular parameters, and (3) provides a physical understanding
of the important molecular interactions at play. This model is applicable to both
nonionic and ionic surfactants, where the effects of the electric double layer
have been taken into account in the latter case. For nonionic surfactants, we
were able to extend our model to predict dynamic surface tension as well. We have
validated our model with tensiometry experiments for various surfactants,
concentrations, and temperatures. In addition, we have validated our model with a
diverse set of literature data, wherein agreement within a few mN M-1 and a
correct prediction of phase change behavior is shown. The model could enable a
more informed design of surfactant systems and serve as the theoretical basis for
theory on more complex surfactant systems such as mixtures.
PMID- 29338269
TI - Reactivity Toward Ag+: A General Strategy to Generate a New Emissive Center from
NIR-Emitting Gold Nanoparticles.
AB - We report a facile strategy for the transformation of single NIR-emitting AuNPs
to dual-NIR-emitting bimetallic Ag@AuNPs based on the robust reactivity toward
Ag(I) ions under mild conditions. The reactivities toward Ag(I) ions were found
to be significantly different between visible- and NIR-emitting glutathione (GSH)
coated AuNPs: the high GSH surface coverage on the 610 nm-emitting AuNPs resulted
in a reversible interaction due to enough surface steric hindrance to resist
Ag(I) ions from interaction with the Au(0) core, whereas the low GSH surface
coverage on the 810 nm-emitting AuNPs led to both antigalvanic reaction and Ag(I)
carboxylate shell formation on the surface of the AuNPs, which were responsible
for the formation of a new emissive center at 705 nm. This strategy was also
demonstrated to exhibit excellent generalization toward various NIR-emitting
AuNPs with surface chemistries containing carboxyl groups, opening a new pathway
of tailoring the optical properties of metallic NPs through surface reactivity.
PMID- 29338270
TI - Effect of calcium on the microstructure and corrosion behavior of microarc
oxidized Mg-xCa alloys.
AB - Magnesium alloys are potential biodegradable implants for biomedical
applications, and calcium (Ca) is one kind of ideal element being examined for
magnesium alloys and biodegradable ceramic coatings owing to its biocompatibility
and mechanical suitability. In this study, microarc oxidation (MAO) coatings were
prepared on Mg-xCa alloys to study the effect of Ca on the microstructure and
corrosion resistance of Mg-xCa alloys and their surface MAO coatings. The
electrochemical corrosion behavior was investigated using an electrochemical
workstation, and the degradability and bioactivity were evaluated by soaking
tests in simulated body fluid (SBF) solutions. The corrosion products were
characterized by scanning electron microscopy, x-ray diffractometry, and Fourier
transform infrared spectrometry. The effects of Ca on the alloy phase
composition, microstructure, MAO coating formation mechanism, and corrosion
behavior were investigated. Results showed that the Mg-0.82Ca alloy and MAO
coated Mg-0.82Ca exhibited the highest corrosion resistance. The number and
distribution of Mg2Ca phases can be controlled by adjusting the Ca content in the
Mg-xCa alloys. The proper amount of Ca in magnesium alloy was about 0.5-0.8 wt.
%. The pore size, surface roughness, and corrosion behavior of microarc oxidized
Mg-xCa samples can be controlled by the number and distribution of the Mg2Ca
phase. The corrosion behaviors of microarc oxidized Mg-Ca in SBF solutions were
discussed.
PMID- 29338271
TI - Analytical, anthropometric and dietary factors associated with the development of
fibrosis in patients with nonalcoholic fatty liver disease.
AB - BACKGROUND: a prolonged non-alcoholic steatohepatitis (NASH) condition can lead
to advanced stages of liver disease and the development of hepatocellular
carcinoma. AIM: to evaluate analytical, anthropometric and dietary factors
associated with the presence of fibrosis as this is the factor that most
influences survival and evolution. METHODS: seventy-six patients with liver
biopsy-diagnosed non-alcoholic fatty liver disease (NAFLD) were included.
Biopsies were scored considering the NASH criteria of Kleiner. Analytical,
anthropometric and dietary (survey) parameters were obtained. NAFLD-FS is a non
invasive fibrosis index and was assessed for each patient. Leptin, adiponectin,
resistin and TNF-alpha serum levels were determined. RESULTS: fifty-six patients
were male (73.7%) and the mean age was 44.5 +/- 11.3 years of age (19-68). Thirty
nine (51.3%) (F1-F2: 84.6%; F3-4: 15.4%) patients had fibrosis in the liver
biopsy. Seventeen females (85%) had fibrosis versus 22 males (39%), which was
statistically significant by univariate analysis (p < 0.01). Patients with
advanced fibrosis were older, with lower platelet counts, lower serum albumin,
greater homeostatic model assessment insulin resistance (HOMA-IR), lower dietary
lipids percentage, higher serum leptin levels and higher NAFLD Fibrosis Score
(NAFLD-FS) values. This index had a negative predictive value of 98% and a
positive predictive value of 60% for the detection of fibrosis. Variables
independently associated with fibrosis (logistic regression) included male gender
(protective factor) (0.09, 95% CI 0.01-0.7; p < 0.05) and HOMA-IR (1.7, 95% CI,
1.03-2.79; p < 0.05). CONCLUSIONS: gender and HOMA-IR were the only independent
factors associated with fibrosis. NAFLD-FS could be considered as an accurate
scoring system to rule out advanced fibrosis.
PMID- 29338272
TI - Morphologic assessment of mandibular anterior teeth root canal using CBCT.
AB - OBJECTIVE: The aim of this study was to evaluate the number and morphological
characteristics of the roots and root canals in mandibular anterior teeth, using
cone beam computed tomography. METHODS AND MATERIALS: In this cross-sectional
study, 1053 anterior mandibular teeth from 200 CBCT scans were evaluated. The
teeth were completely developed and should have had no fillings in the root or
crown. The teeth were investigated in terms of the number of roots and root
canals, the location of the apical foramen, the distance of the apical foramen to
the anatomical apex, root length, crown length, dilacerations and the type of
canals according to Vertucci's classification. RESULTS: 87.9% of teeth had one
root canal and of all of the teeth, three canines (0.3%) were found that had two
roots. In 80.3% (n: 848) of cases the foramen apical location was central, then
the buccal (9.3%), lingual (3.9%), distal (3.8%), and mesial (2.7%). The type of
root canals, according to Vertucci's classification, with respect to prevalence,
included type I (88.2%), type III (8.1%), type II (3.3%), type V (0.3%), and type
VI (0.1%), respectively. In terms of the characteristics investigated, bilateral
symmetry was observed. Dilaceration was not seen in any of the teeth. CONCLUSION:
The root canal morphology of mandibular anterior teeth has great diversity that
may differ between different races, and should be considered by all dentists in
order to achieve the best dental treatment.
PMID- 29338273
TI - Adverse drug reactions of non-opioid and opioid analgesics reported to Croatian
national authority from 2007 to 2014.
AB - OBJECTIVE: Adverse drug reactions (ADRs) are commonly observed in the health
services because of system weaknesses and individual errors. Analgesics are
widely used and it can be expected that with the increased use one can expect
increased number of ADRs of analgesics. The aim of this study was to analyze ADRs
of non-opioid and opioid analgesics reported to the Croatian Agency for Medicinal
Products and Medical Devices (HALMED) from 2007 to 2014. METHODS: HALMED provided
data on generic drug name, year of the ADR report, type of report, institution,
reporting person, patient's age, sex and ADR type. RESULTS: In the analyzed
period 796 ADRs of analgesics were reported, of which 367 (46%) were serious
ADRs. Number of ADR reports was continuously increasing during the analyzed
period. There were 20 analgesics that had >=5 reports, making 597 (75%) of all
ADR reports for analgesics. The most common adverse reaction reports of those 20
analgesics referred to individual drugs (n=16; 80%). Most of the ADR reports were
filed by physicians (n=257; 43%), followed by pharmacists (n=252; 42%). Most side
effects (n=572; 96%) were reported spontaneously through appropriate forms by
patients or health professionals. ADRs were most commonly reported in women
(n=352; 59%) and most of them have occurred in adults (n=354; 59%). The most
common ADRs of opioid and non-opioid analgesics have been reported on the skin
and mucous membranes. Most serious ADRs were result of action of opioid
analgesics. CONCLUSION: Number of ADR reports in Croatia is continuously
increasing and a considerable number of them refers to serious ADRs. To keep
better track of medications and ADRs it is necessary to educate and encourage
health professionals and patients in reporting side effects.
PMID- 29338274
TI - Frequency and correlation of lip prints, fingerprints and ABO blood groups in
population of Sriganganagar District, Rajasthan.
AB - OBJECTIVE: To investigate the frequency and uniqueness of different lip print
patterns, fingerprint patterns in relation to gender and ABO Rh blood groups
among a semi-urban population of Sriganganagar, Rajasthan. MATERIALS AND METHODS:
The study was conducted on 1200 healthy volunteers aged 18-30 years. The
cheiloscopic and dermatographic data of each subject were obtained and were
analysed according to the Suzuki and Tsuchihashi and Henry systems of
classification, respectively. Two forensic experts analyzed the patterns
independently. The ABO Rh blood group was also recorded for each subject. The Chi
square statistical analysis was done and tests were considered significant when p
value <0.001 and Cohen kappa test was applied to analyze inter-observer
reliability. RESULTS: The B+ blood group was noted as most common in both genders
while least common were A- among males and AB- in females. Type II lip pattern
was most predominant while the least common was Type I' in males and Type I' and
Type V in females. The UL fingerprint pattern was the most common, while RL was
least noted in both genders. All the fingerprint patterns showed correlation with
different lip print patterns. A correlation was found between different blood
groups and lip print patterns except Type I (vertical) lip pattern. A positive
correlation was observed between all the blood groups and fingerprint patterns,
except for RL pattern. CONCLUSION: There is an association between lip print
patterns, fingerprint patterns and ABO blood groups in both the genders. Thus,
correlating the uniqueness of these physical evidences sometimes helps the
forensic team members in accurate personal identification or it can at least
narrow the search for an individual where there are no possible data referring to
the identity of the subject.
PMID- 29338275
TI - Metformin use associated with protective effects for ocular complications in
patients with type 2 diabetes - observational study.
AB - OBJECTIVE: The aim was to study the association of the use of an oral
antihyperglycemic agent metformin with the presence of ocular complications in
patients with type 2 diabetes (T2D). METHODS: Medical records were reviewed for
234 patients with diagnosed T2D. 81.2% (n=190) patients were using metformin and
18.8% (n=44) using other oral antihyperglycemic agents. Plasma glucose
concentration, glycated haemoglobin, and the presence of ocular complications in
patients treated with metformin were compared to those in patients treated with
other oral antihyperglycemic agents. RESULTS: Ocular complications occurred in 65
patients (27.8%). Patients treated with metformin had fewer ocular complications
compared to patients treated with other oral antihyperglycemic agents
(chi2=19.985; p<0.0001). After adjustment for gender, age, duration of T2D, serum
concentration of cholesterol, smoking, body mass index and presence of other
diseases, treatment with metformin decreased the odds of both glaucoma (OR=0.14,
95% CI: 0.03-0.57, p=0.006) and diabetic retinopathy (OR=0.33, 95% CI: 0.14-0.82,
p=0.017) compared with other oral antihyperglycemic agents. CONCLUSION: Our
results suggest that metformin may have a protective effect on ocular
complications, especially glaucoma, in patients with T2D. The effects of
metformin either regarding prevention of ocular complications or ocular
complications already developed in patients with T2D, should be further
investigated.
PMID- 29338276
TI - Evaluation of the water sorption of luting cements in different solutions.
AB - OBJECTIVE: To evaluate and compare the water sorption of three luting cements in
three different solutions: distilled water and artificial saliva with different
pH values (7.4 and 3.0). MATERIALS AND METHODS: Resin-modified glass-ionomer
cement (GC Fuji Plus) and two resin cements (Multilink Automix and Variolink II)
were used. A total of 45 specimens - 15 specimens (15x1 mm) for each cement were
prepared according to ISO standard 4049:2009. The water sorptions of the cements
were calculated by weighing the specimens before and after immersion and
desiccation. RESULTS: . Nonparametric statistic methods were applied. GC Fuji
Plus cement showed significantly higher values of water sorption in all three
solutions of both resin cements (p<0.009) and significantly higher values of
sorption in artificial saliva pH 3.0. Multilink Automix showed significantly
higher values of water sorption compared with Variolink II in artificial saliva
pH 7.4, and higher values of sorption in this solution compared with pH value
3.0. CONCLUSION: Water sorption values are mainly influenced by the proportion of
hydrophilic matrix, the type and composition of filler, and the pH value of
solutions.
PMID- 29338277
TI - Assessment of inpatient psychiatric readmission risk among patients discharged on
an antipsychotic polypharmacy regimen: A retrospective cohort study.
AB - OBJECTIVE: Patients are frequently prescribed multiple antipsychotic medications,
leading to higher healthcare costs and increased risk for side effects. The
efficacy of multiple versus single antipsychotics to prevent acute relapse,
measured by incidence of inpatient readmission, is investigated in Arizona, USA.
METHOD: A retrospective chart review compared socio-demographic and clinical data
from 1,010 patients discharged on a single and 377 discharged on multiple
antipsychotic medications. Case management records were reviewed for readmission
within one year of discharge. RESULTS: Younger age, diagnosis of Schizophrenia or
Schizoaffective Disorder, prescription of mood stabilizer, shorter length of
stay, and discharge to residential treatment or crisis recovery unit were
associated with multiple antipsychotics at discharge. Readmission rates of the
single (13.7%) versus multiple (15.9%) antipsychotic groups were not
statistically different (p=0.286). Logistic regression analysis established that
only age (younger) and the prescription of a mood stabilizer at discharge were
significant predictors for increased risk for readmission (p=0.010 and p=0.049,
respectively). A Cox survival analysis supported these findings. CONCLUSIONS:
Concomitant antipsychotic polypharmacy at discharge did not reduce readmission
risk over a one-year period. Given the increased risk of side effects and
financial costs of polypharmacy, this study did not provide evidence to support
this practice. Strikingly, only two variables predicted readmission risk, younger
age and prescription of mood stabilizer. Although practitioners should follow
practice guidelines more closely to prevent unnecessary exposure to potentially
lethal side effects of antipsychotic polypharmacy, further studies are needed to
better identify patients at high risk for readmission.
PMID- 29338278
TI - The effects of interprofessional diabetes education on the knowledge of medical,
dentistry and nursing students.
AB - OBJECTIVES: Interprofessional teamwork is best attained through education that
promotes mutual trust and effective communication. The primary aim of the study
was to evaluate the impact of interprofessional learning on knowledge about
diabetes. METHODS: The cross-sectional study included students of medicine,
dentistry and nursing at the Faculty of Medicine Foca, Bosnia and Herzegovina.
The students were randomly allocated into one of two groups. Group 1 attended an
interprofessional course on diabetes while group 2 was divided into three
subgroups and each of the subgroups attended an uniprofessional diabetes course.
The measuring instrument used in the course in order to assess the participants'
knowledge about diabetic care was a test containing multiple-choice questions
about diabetes. The Interprofessional Questionnaire was used to explore the
attitudes, views, values and beliefs of students regarding interprofessional
education (IPE). RESULTS: No statistically significant difference in total score
on the test was found between the groups at baseline, but at follow-up the
difference was highly statistically significant (F=10.87; p=0.002). The students
from Group 1 had better results (21.82 points), compared to Group 2 (18.77
points). The statistically significant difference was observed in mean values (t=
3.997; p=0.001), between Groups 1 and 2; the students from Group 1 obtained 20.42
points, which is considered to indicate a respectively positive self-assessment
of communication and teamwork skills. However, Group 2 indicated a negative self
assessment of communication and teamwork skills. CONCLUSION: The findings suggest
that IPE activities may provide health profession students with valuable
collaborative learning opportunities.
PMID- 29338279
TI - The chondrocoracoideus muscle: A rare anatomical variant of the pectoral area.
AB - OBJECTIVE: The study adds important information regarding the descriptive anatomy
of a very rarely reported unilateral chondrocoracoideus muscle (of Wood).
Additionally it highlights the concomitant muscular and neural alterations. CASE
REPORT: The current case presents the occurrence of a chondrocoracoideus muscle
situated left-sided, as an extension of the abdominal portion of the pectoralis
major muscle (PM). The chondrocoracoideus coexisted with a contralateral atypical
PM, partially blended with the clavicular fibers of the deltoid muscle. There was
an accessory head of the biceps brachii while the palmaris longus was absent on
the right side of a 78-year-old Greek male cadaver. CONCLUSION: The above
mentioned muscular abnormalities are shown as disturbances of embryological
pectoral muscle development, and their documentation is essential in order to
increase awareness among clinicians of their potential impact on the diagnosis
and treatment of several pathologies.
PMID- 29338280
TI - Variable skeletal anatomical features of acromegaly in the skull and
craniocervical junction.
AB - OBJECTIVE: This study adds important information regarding the morphological
alterations caused by growth hormone hypersecretion in the skull and
craniocervical junction (CCJ). A variably asymmetric skull due to acromegaly
coexists with expansion of the paranasal sinuses and multiple Wormian bones. CASE
REPORT: A pathologically asymmetric dry skull of a European male, aged 38 years
at death, with cranial vault and skull base thickening is described. The
extensive paranasal sinus pneumatization caused a generalized thinning of the
bony walls. The sphenoid sinus expanded intraorbitally, leading to sella
enlargement. The orbital asymmetry coexisted with platybasia and hypoplasia of
the occipital condyles and the odontoid process. Facial skeleton elongation and
mandibular overgrowth were combined with prognathism, malocclusion and overbite.
CONCLUSION: Skull and CCJ alterations are of paramount importance when selecting
the surgical approach, if surgery is indicated. Consecutively, detailed
preoperative evaluation and planning is essential. During surgery, skilled and
experienced neurosurgeons recognize anatomical landmarks, use neuronavigation and
micro-instrumentation in order to remain on the midline avoiding any potential
lethal vascular injury.
PMID- 29338281
TI - Severe vertebral erosion by chronic contained rupture of an abdominal aortic
aneurysm.
AB - No abstract available.
PMID- 29338282
TI - Spontaneous closure of a full thickness macular hole.
AB - No abstract available.
PMID- 29338283
TI - Intussuscepted Meckel's diverticulum within its own lumen.
AB - No abstract available.
PMID- 29338284
TI - Healing invisible wounds - have we done enough to help the victims of wartime
rape?
AB - No abstract available.
PMID- 29338285
TI - Response to whether the definition of the term "children born of war" and
vulnerabilities of children from recent conflict and post-conflict settings
should be broadened.
AB - No abstract available.
PMID- 29338286
TI - Reflections on the definition and categorization of "Children Born of War".
AB - No abstract available.
PMID- 29338288
TI - Transcranial magnetic stimulation (TMS) safety: a practical guide for
psychiatrists.
AB - OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) is increasingly
being utilised as a treatment option for depression, and with this comes a need
for a practical review of safety issues intended for clinicians. This article
provides an overview of the current literature regarding safety issues with rTMS
for depression, and provides recommendations for clinical practice. CONCLUSIONS:
Overall, rTMS is a well-tolerated treatment with common side effects (such as
headache or local pain at the site of stimulation) being mild. Severe adverse
effects, such as seizures, hearing impairment or mania, are uncommon. Certain
populations, including adolescents, pregnant women, older adults and those with
metal/electronic implants, require special consideration when prescribing and
monitoring treatment courses. With adequate assessment and monitoring processes,
rTMS can be administered safely in a large proportion of depressed patients.
PMID- 29338289
TI - A systematic review of risk factors for methamphetamine-associated psychosis.
AB - OBJECTIVE: Chronic methamphetamine use is commonly associated with the
development of psychotic symptoms. The predictors and correlates of
methamphetamine-associated psychosis are poorly understood. We sought to
systematically review factors associated with psychotic symptoms in adults using
illicit amphetamine or methamphetamine. METHODS: A systematic literature search
was performed on MEDLINE (OVID), PsycINFO and EMBASE databases from inception to
8 December 2016. The search strategy combined three concept areas:
methamphetamine or amphetamine, psychosis and risk factors. Included studies
needed to compare adults using illicit methamphetamine or amphetamine, using a
validated measure of psychosis, on a range of risk factors. Of 402 identified
articles, we removed 45 duplicates, 320 articles based on abstract/title and 17
ineligible full-text articles, leaving 20 included studies that were conducted in
13 populations. Two co-authors independently extracted the following data from
each study: country, setting and design; participant demographic and clinical
details; sample size; measure/s used and measures of association between
psychosis outcomes and risk factors. Individual study quality was assessed using
a modified Newcastle-Ottawa Scale, and strength of evidence was assessed using
GRADE criteria. RESULTS: Frequency of methamphetamine use and severity of
methamphetamine dependence were consistently found to be associated with
psychosis, and sociodemographic factors were not. There was inconsistent evidence
available for all other risk factors. Individual study quality was low-moderate
for the majority of studies. Heterogeneity in study outcomes precluded
quantitative synthesis of outcomes across studies. CONCLUSION: The most
consistent correlates of psychotic symptoms were increased frequency of
methamphetamine use and dependence on methamphetamine. The findings of this
review highlight the need for targeted assessment and treatment of
methamphetamine use in individuals presenting with psychosis.
PMID- 29338290
TI - Barking Our Way Into the Year of the Dog: Public Health Benefits and Challenges.
PMID- 29338291
TI - Indications for Surgical Repair of Type 1 Laryngeal Cleft.
AB - OBJECTIVES: Type 1 laryngeal cleft (T1LC) is a congenital deficiency in the
posterior glottis, resulting in a communication between the hypopharynx and
glottis. No consensus treatment paradigm exists for timing and criteria for
patient selection for surgical repair. Our goal is to assess whether patient
characteristics can help predict improvement after surgery. METHODS: After
Institutional Review Board exemption, a retrospective chart review was performed
for patients undergoing surgery to diagnose a T1LC. Charts were examined for age,
presenting symptoms, comorbidities, pre/postoperative videoflouroscopic swallow
study reports, and outcomes. RESULTS: Ninety-seven patients with clinical
suspicion for T1LC underwent direct laryngoscopy and bronchoscopy, and 63 (64%)
were diagnosed with a T1LC. Twenty-two patients (63%) undergoing surgery achieved
clinical or radiographic improvement. There was no difference in average age,
aspiration, or penetration between clinical improvement and no improvement
groups. Of 13 patients with comorbidities that increase their risk of aspiration,
12 were significantly improved. There were 5 complications, which were managed
conservatively. CONCLUSIONS: Our experience supports the repair of T1LC repair at
time of diagnostic laryngoscopy if satisfactory improvement is not noted with
conservative treatment. This should be performed without segregation for age,
comorbidities, or degree of dysphagia. Our technique is performed with minimal
complications and achieves satisfactory results.
PMID- 29338293
TI - Betrixaban: A New Oral Factor Xa Inhibitor for Extended Venous Thromboembolism
Prophylaxis in High-Risk Hospitalized Patients.
AB - OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of
the factor Xa (FXa) inhibitor betrixaban for extended-duration prophylaxis of
acute medically ill patients with venous thromboembolism (VTE) risk factors. DATA
SOURCES: A MEDLINE/PubMed (January 1990 to October 2017) search was conducted
using the following keywords: betrixaban, PRT054021, FXa inhibitor, novel oral
anticoagulant, NOAC, direct oral anticoagulant, DOAC, and target specific oral
anticoagulant, TSOAC. References of identified articles were searched by hand for
additional relevant citations. STUDY SELECTION AND DATA EXTRACTION: We included
English-language articles evaluating betrixaban pharmacology, pharmacokinetics,
efficacy, or safety in human subjects for VTE prophylaxis. DATA SYNTHESIS:
Betrixaban is a FXa inhibitor that decreases prothrombinase activity and thrombin
generation. Betrixaban efficacy and safety has been compared with that of
enoxaparin for prophylaxis of VTE in acutely ill medical patients. In the APEX
trial and substudies, extended-duration betrixaban was superior in efficacy to
standard-duration enoxaparin in patients at high risk for VTE, including those
with elevated D-dimer levels (>=2* upper limit of normal) and of older age (>=75
years). Betrixaban is noninferior to enoxaparin in rates of major bleeding, but
the former is associated with more clinically relevant nonmajor bleeding events.
CONCLUSION: Betrixaban is the first oral agent approved for extended-duration VTE
prophylaxis in acutely ill hospitalized patients. Extended-duration
thromboprophylaxis with betrixaban reduces the risk of VTE compared with standard
duration thromboprophylaxis with enoxaparin but is associated with increased risk
of bleeding.
PMID- 29338292
TI - Temporalis Fascia Transplantation for Sulcus Vocalis and Vocal Fold Scar: Long
Term Outcomes.
AB - OBJECTIVE: Sulcus vocalis and vocal fold scar involve derangement of the
superficial lamina propria of the vocal fold, which results in significant
dysphonia. Many options exist for treatment, most of which have unsatisfactory
and unpredictable outcomes. Autologous transplantation of temporalis fascia into
the vocal fold (ATFV) has the potential to be a better treatment option, but long
term outcomes have not been well studied. METHODS: Retrospective chart review and
patient survey. Twenty-one patients diagnosed with vocal fold scar or sulcus
vocalis and treated with ATFV with at least 1-year follow-up were included. Voice
Handicap Index 10 (VHI-10) questionnaires were collected preoperatively and 6
months postoperatively. Patients were reached at the time of the study to
complete another VHI-10 and a Likert scale survey. RESULTS: The mean decrease in
VHI-10 scores between preoperation and 6 months postoperation was 8.35 ( P <
.001). From preoperation to the time of the study (average 44 months; range, 12
72 months), the VHI decreased 13.53 ( P < .001). Eighty-eight percent of patients
reported they would recommend this surgery to others with the same diagnosis.
Only 1 minor self-limited complication occurred. CONCLUSION: Autologous
transplantation of temporalis fascia into the vocal fold for the treatment of
vocal fold scar and sulcus vocalis is a safe surgery with good long-term outcomes
and high patient satisfaction.
PMID- 29338294
TI - The importance of clinical observation: A case of subtle tardive dyskinesia with
paliperidone palmitate.
PMID- 29338295
TI - A Scoping Review of Inclusive Out-of-School Time Physical Activity Programs for
Children and Youth With Physical Disabilities.
AB - The objective of this study was to comprehensively evaluate inclusive out-of
school time physical activity programs for children/youth with physical
disabilities. A search of the published literature was conducted and augmented by
international expertise. A quality appraisal was conducted; only studies with
quality ratings >=60% informed our best practice recommendations. Seventeen
studies were included using qualitative (n = 9), quantitative (n = 5), or mixed
(n = 3) designs. Programs had a diversity of age groups, group sizes, and
durations. Most programs were recreational level, involving both genders.
Rehabilitation staff were the most common leaders. Outcomes focused on social
skills/relationships, physical skill development, and psychological well-being,
with overall positive effects shown in these areas. The best practice
recommendations are consistent with an abilities-based approach emphasizing
common group goals and interests; cooperative activities; mastery-oriented,
individualized instruction; and developmentally appropriate, challenging
activities. Results indicate that inclusive out-of-school time physical activity
programs are important for positive psychosocial and physical skill development
of children/youth with physical disabilities.
PMID- 29338296
TI - Tips and tricks in axillary cannulation.
PMID- 29338297
TI - Unusual case of left atrial myxoma with gastroesophageal junction adenocarcinoma.
AB - Cardiac myxomas are rare tumors. Esophageal adenocarcinomas are common tumors of
the gastrointestinal tract. Simultaneous occurrence of these tumors has not been
reported. A 52-year-old gentleman presented to our hospital with dysphagia and
was diagnosed with esophageal adenocarcinoma. Routine echocardiography discovered
a cardiac tumor in the left atrium. The cardiac tumor was surgically removed and
biopsy confirmed a myxoma. We removed the cardiac tumor as the first step and
then initiated neoadjuvant chemotherapy. It is ideal to constitute a
multidisciplinary team to decide on the course of treatment in such cases.
PMID- 29338298
TI - Coronary and arch hybrid surgery in a patient with infrarenal aortic occlusion.
AB - A 65-year-old gentleman with claudication underwent contrast-enhanced computed
tomography. The scan showed occlusion of the infrarenal abdominal aorta and a 6.0
* 3.7 cm saccular zone-3 arch aneurysm. The left ventricular ejection fraction
was 35% and a coronary angiogram revealed triple-vessel disease. In view of the
patient's high risk with EuroSCORE II 20.34%, coronary artery surgery was
combined with hybrid type I arch aneurysm repair. An endovascular stent was
delivered in an antegrade manner. Open heart surgery and a hybrid type I arch
intervention can be performed simultaneously through a midline sternotomy
approach.
PMID- 29338299
TI - Mitral valve replacement via a left thoracotomy in dextrocardia and situs
solitus.
AB - Dextrocardia with situs solitus and severe mitral regurgitation is a rare
clinical presentation which posse a surgical challenge and requires specific
preoperative planning. A 54-year-old women with this anatomy, multiple thoracic
procedures, and severe mitral valve regurgitation underwent successful mitral
valve replacement with a 27-mm mechanical prosthesis through a left thoracotomy
under ventricular fibrillation, on the basis of computed tomography findings. We
emphasize the importance of preoperative planning and a surgical approach through
a left thoracotomy and under ventricular fibrillation.
PMID- 29338300
TI - Penetrating injury of the ascending aorta complicating a sternal biopsy.
AB - Bone marrow aspiration and trephine biopsy are considered safe procedures. Some
serious but rare adverse events directly attributable to these procedures have
been related in a few reports in the literature. We report a rare case of
ascending aortic injury following a sternal trephine biopsy.
PMID- 29338301
TI - Coronary artery perforation complicating percutaneous coronary intervention.
AB - Background Coronary artery perforation is a rare but serious complication of
percutaneous coronary interventions. We aimed to evaluate the management of
coronary artery perforation in Sulaimaniyah, Iraq. Methods A retrospective review
of our medical records from 2009 to 2016 identified 24 patients (15 males, 9
females) with coronary artery perforation. Mean age was 60 +/- 9.2 years (range
40-74 years). Standard diagnostic angiography or percutaneous interventions were
performed. Coronary artery perforation was diagnosed by worsening of symptoms,
hypotension, or angiographic evidence of type I (extraluminal crater), II
(myocardial or pericardial blushing), or III (contrast streaming or cavity
spilling) perforation. Stenosis was graded as >85%, 60%-85%, or < 60%. Once
coronary artery perforation was diagnosed, heparin was reversed, antiplatelets
were stopped, and pericardial effusions were aspirated. Type II and III coronary
artery perforations were sealed using covered stents or repeated brief balloon
inflations. Results The most frequently injured artery was the left anterior
descending ( n = 14, 58.3%). Type II and III coronary artery perforations
constituted the majority ( n = 18, 75%). Thirteen (54.2%) patients had severe
coronary stenosis. Perforations were caused by stents ( n = 10), angioplasty
wires ( n = 8), and balloons ( n = 6). Fifteen perforations were sealed with
covered stents, 2 by balloon inflations, and 7 resolved spontaneously.
Pericardial effusion was drained in 13 (54.2%) patients. No patient required
surgery, and none died. Conclusion The low rate and early management of coronary
artery perforations, mainly by covered stents, were the hallmarks of this study.
PMID- 29338303
TI - Evaluation of Preprocedural Laboratory Parameters as Predictors of Drug-Eluting
Stent Restenosis in Coronary Chronic Total Occlusion Lesions.
AB - This retrospective, single-center study assessed the prognostic value of several
emerging inflammatory markers as predictors of in-stent restenosis (ISR) after
drug-eluting stent implantation for coronary chronic total occlusion (CTO)
lesions. Consecutive patients (n = 416) who underwent successful percutaneous
coronary intervention (PCI) for documented CTO lesions and with follow-up
angiography were enrolled. Preprocedural high-sensitivity C-reactive protein
(hsCRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio
(PLR), and red cell distribution width (RDW) were analyzed. At mean follow-up of
14.4 +/- 3.3 months, ISR occurred in 72 patients. Compared with the non-ISR
group, preprocedural hsCRP level, PLR, NLR, and RDW were significantly higher in
the ISR group. The ISR group also had significantly greater proportions of
patients with diabetes and smoking history, lower estimated glomerular filtration
rate, higher low-density lipoprotein cholesterol (LDL-C) level and neutrophil
count, longer stent length, and higher rate of severe dissection. In multivariate
analysis, NLR (odds ratio [OR]: 3.110; 95% confidence interval [CI], 2.102-4.063;
P < .001) and PLR (OR: 1.029; 95% CI, 1.016-1.143; P < .001) were independent
predictors of ISR, along with LDL-C level and stent length. In conclusion, higher
preprocedural NLR and PLR levels were independent risk factors for the
development of ISR in patients who underwent PCI for CTO lesions.
PMID- 29338302
TI - Neurotransmitter Pathway Genes in Cognitive Decline During Aging: Evidence for
GNG4 and KCNQ2 Genes.
AB - BACKGROUND/RATIONALE: Experimental studies support the role of neurotransmitter
genes in dementia risk, but human studies utilizing single variants in candidate
genes have had limited success. METHODS: We used the gene-based testing program
Versatile Gene-based Association Study to assess whether aggregate variation
across 6 neurotransmitter pathways influences risk of cognitive decline in 8159
cognitively normal elderly (>=65 years old) adults from 3 community-based
cohorts. RESULTS: Common genetic variation in GNG4 and KCNQ2 was associated with
cognitive decline. In human brain tissue data sets, both GNG4 and KCNQ2 show
higher expression in hippocampus relative to other brain regions; GNG4 expression
decreases with advancing age. Both GNG4 and KCNQ2 show highest expression in
fetal astrocytes. CONCLUSION: Genetic variation analyses and gene expression data
suggest that GNG4 and KCNQ2 may be associated with cognitive decline in normal
aging. Gene-based testing of neurotransmitter pathways may confirm and reveal
novel risk genes in future studies of healthy cognitive aging.
PMID- 29338304
TI - Investigation of the use of external aluminium targets for portal imaging in a
medical accelerator using Geant4 Monte Carlo simulation.
AB - OBJECTIVE: To install a low-Z target on the wedge tray mount of a medical linear
accelerator to create a new image beam and to confirm image contrast enhancement.
METHODS: Experimental low-energy photon beams were produced with the linac
running in the 6 MeV electron mode and with a low-Z target installed on the wedge
tray mount [denoted 6 MeV (low-Z target)]. Geant4 Monte Carlo simulation was
performed to analyse the energy spectrum and image contrast of a 6 MeV (low-Z
target) beam. This study modelled the 6 MeV (low-Z target) beam and the 6 MV
(megavoltage) radiotherapy photon beam and verified model validity by
measurement. In addition, a contrast phantom was modelled to quantitatively
compare the image contrasts of the 6 MeV (low-Z target) beam and the 6 MV
radiotherapy photon beam. A low-Z target was fabricated to generate low-energy
photons (25-150 keV) from incident electrons, and a portal image of the Alderson
RANDO phantom was acquired using a clinical linear accelerator for qualitative
analysis. RESULTS: The measured and calculated percentage depth dose of the 6 MV
photon and 6 MeV (Al) beams were consistent within 1.5 and 1.6%, respectively,
and calculated lateral profiles of the 6 MV photon beam and the 6 MeV (Al) beam
were consistent with the measured results within 1.5 and 1.9%, respectively.
Although low-energy photons (25-150 keV) of the 6 MV photon beam were only 0.3%,
the Be, C, and Al low-Z targets, but not the Ti target, generated 34.4 to 38.5%
low-energy photons. In 5 to 20 cm water phantoms, contrast of the 6 MeV (Al) beam
was approximately 1.16 times greater than that of the 6 MV beam. The contrasts of
6 MeV (Al) and 6 MV photon beams in the 20 cm water phantom were ~34% lower than
those in the 5 cm water phantom. 6 MeV (Al)/CR (computed radiography) images of
the human body phantom were more vivid and detailed than 6 MV/EPID (electronic
portal imaging device) and 6 MeV (Al)/EPID images. CONCLUSION: The experimental
beam with a low-Z target, which was simply installed on the wedge tray mount of
the radiotherapy linear accelerator, generated significantly more low-energy
photons than the 6 MV radiotherapy photon beam, and provided better quality
portal images. Advances in knowledge: This study shows that, unlike the existing
low-Z beam studies, a low-Z target can be installed outside the head of a linear
accelerator to improve portal image quality.
PMID- 29338306
TI - Biomarkers for assessing the effectiveness of immunotherapy in breast cancer.
PMID- 29338305
TI - Safety and feasibility of prostate stereotactic ablative radiotherapy using
multimodality imaging and flattening filter free.
AB - OBJECTIVE: To investigate feasibility and safety of stereotactic ablative
radiotherapy in the management of prostate cancer while employing MR/CT fusion
for delineation, fiducial marker seeds for positioning and Varian RapidArc with
flattening filter free (FFF) delivery. METHODS: 41 patients were treated for low
intermediate risk prostate cancer with initial prostate-specific antigen of <=20
ng ml-1, Gleason score 6-7. Patients had MR/CT fusion for delineation of prostate
+/-seminal vesicles. CT/MR fusion images were used for delineation and planned
using flattening filter free modality. Verification on treatment was cone beam CT
imaging with fiducial markers for matching. Patients had Radiation Therapy
Oncology Group scoring for genitourinary and gastointestinal symptoms at
baseline, week 4, 10 and 18. RESULTS: Clinically acceptable plans were achieved
for all patients, all plans achieved the objective clinical target volume D99% >=
95%, and for planning target volume D95% >= 95%. Rectum dose constraints were met
for 95.1% for V18 Gy <= 35%, 80% V28 Gy <= 10%. A total of 32 (78.0%) plans
achieved all rectum dose constraints. Grade 1 acute genitourinary symptoms were
53.7% of patients at baseline, 90.2% [95% CI (76.8-97.3%)] (p = 0.0005) at
treatment 5, falling to 78.0% (62.4-89.4%) at week 4, and 75.0% (58.8-87.3%) by
week 10 and 52.5% (36.1-68.5%) (p = 1.00) at week 18. Acute gastrointestinal
symptoms were 5% at baseline, 46.3% [95% CI (30.7-62.6%)] at treatment 5, week 4
43.9% [95% CI (28.5-60.3%)], week 10 25.0% (11.1-42.3%), and declined slightly by
week 18 [-20.095% CI (12.7-41.2)] p = 0.039. Overall 75.6% (31/41) of patients
experienced Grade 1-2 toxicity during or after treatment. CONCLUSION: This
planning and delivery technique is feasible, safe and efficient. A homogeneous
dose can be delivered to prostate with confidence, whilst limiting high dose to
nearby structures. The use of this technology can be applied safely within
further randomized study protocols. Advances in knowledge: Multimodality imaging
for delineation and linac-based image-guided RT with FFF for the treatment of
prostate stereotactic ablative radiotherapy.
PMID- 29338307
TI - The impact of prehabilitation on post-surgical complications in patients
undergoing non-urgent cardiovascular surgical intervention: Systematic review and
meta-analysis.
AB - Introduction Cardiac surgery is an aggressive procedure, inducing a great level
of stress and disturbance to the homeostasis of the organism and underlying
several postoperative complications. Surgical prehabilitation comprises pre
operative physical conditioning designed to improve the physiological and
functional capacities of the individual, prepare the organism for surgical stress
and reduce the risk of postoperative morbidity. Aim This systematic review and
meta-analysis is aimed at evaluating the ability of prehabilitation to prevent
post-surgical complications in cardiac patients. Methods We selected studies
conducted among patients who were waiting for non-urgent cardiac surgical
procedures, where a comparison between prehabilitation and standard treatment was
made. A total of 3650 possible studies were researched, of which eight were
selected for inclusion. Results A reduction in the number of complications in the
groups submitted to prehabilitation (odds ratio = 0.41; 95% confidence interval
(CI): 0.28-0.62; p < 0.001; I2 = 0%) was observed, as well as a significant
increase in maximal inspiratory pressure (standard mean difference (SMD) = 0.66;
95% CI: 0.35-0.96; p < 0.001; I2 = 58%), a non-significant decrease in the length
of stay (SMD = -0.56; 95% CI: -1.13, 0.01; p = 0.05; I2 = 93%), a non-significant
increase in the distance walked by the intervention group in the six-minute walk
test (SMD = 0.89; 95% CI -0.06, 1.84; p = 0.07) and a lack of effect on
mechanical ventilation time (SMD = -0.03; 95% CI: -0.22, 0.16; p = 0.75; I2 =
0%). Conclusion Prehabilitation reduces the number of post-surgical complications
and increases maximal inspiratory pressure; a reduction in the length of stay and
an improvement of functional capacities are also probable.
PMID- 29338308
TI - Calcium supplement is a major concern for patients with cardiovascular diseases.
PMID- 29338311
TI - Sinophobia. Anxiety, violence, and the making of Mongolian identity, by Franck
Bille.
PMID- 29338309
TI - Oral microbiota reduce wound healing capacity of epithelial monolayers,
irrespective of the presence of 5-fluorouracil.
AB - Oral mucositis is still one of the most painful side effects of chemotherapeutic
treatment and a mounting body of evidence suggests a key role for the oral
microbiome in mucositis development. However, the underlying mechanisms remain
elusive. In this work, we have investigated the interactions between the host,
the microbiome, and chemotherapeutic treatments in more detail. The effect of 5
fluorouracil, commonly inducing mucositis, was assessed on a co-culture model
that consists of an epithelial cell layer and a biofilm derived from oral
microbiota from different types of samples (saliva, buccal swabs and tongue
swabs) and donors (healthy individuals and patients suffering from mucositis).
After 24 h co-incubation, all oral microbial samples were found to reduce wound
healing capacity with 26 +/- 15% as compared with untreated condition. Compared
with saliva and tongue samples, buccal samples were characterized by lower
bacterial cell counts and hence higher wound healing capacity. For samples from
healthy individuals, an inverse correlation was observed between bacterial cell
counts and wound healing capacity, whereas for patients suffering from mucositis
no correlation was observed. Moreover, patient-derived samples had a less diverse
microbial community and higher abundances of pathogenic genera. No major impact
of 5-fluorouracil on wound healing capacity or the composition of the microbiome
was seen at physiologically relevant concentrations in the mouth. In conclusion,
bacterial cell count is inversely correlated with wound healing capacity, which
emphasizes the importance of oral hygiene during oral wound healing in healthy
individuals. However, future research on extra measures besides oral hygiene is
needed to assure a good wound healing during mucositis, as for patients the
bacterial composition seems also crucial. The direct effect of 5-fluorouracil on
both the microbiome and wound healing is minimal, pointing to the importance of
the host and its immune system in chemotherapy-induced microbial shifts. Impact
statement Chemotherapy-induced oral mucositis has a major impact on the quality
of life of patients. The additional costs and treatment time associated with this
pathology are significant. Although the pathology of the disease is well
understood, the role and importance of oral microbiota currently are less clear.
In this study, we focused on the effect of oral microbiota on wound healing, the
final phase of oral mucositis, during 5-FU exposure. We show that the bacterial
load and composition have a major impact on the healing process in contrast to 5
FU which only marginally slows down healing. This emphasizes the importance of
good oral health care during oral mucositis to minimize bacterial load around the
oral lesions. However, since we show that also the composition of the oral
microbiome plays a role in wound recovery, the identification of specific
pathogenic species or their metabolites might be worthwhile to allow proper
treatment.
PMID- 29338310
TI - Therapy-Induced Plasticity in Chronic Aphasia Is Associated with Behavioral
Improvement and Time Since Stroke.
AB - Cortical reorganization after stroke is thought to underlie functional
improvement. Patterns of reorganization may differ depending on the amount of
time since the stroke or the degree of improvement. We investigated these issues
in a study of brain connectivity changes with aphasia therapy. Twelve individuals
with chronic aphasia participated in a 6-week trial of imitation-based speech
therapy. We assessed improvement on a repetition test and analyzed effective
connectivity during functional magnetic resonance imaging of a speech observation
task before and after therapy. Using structural equation modeling, patient
networks were compared with a model derived from healthy controls performing the
same task. Independent of the amount of time since the stroke, patients
demonstrating behavioral improvement had networks that reorganized to be more
similar to controls in two functional pathways in the left hemisphere.
Independent of behavioral improvement, patients with remote infarcts (2-7 years
poststroke; n = 5) also reorganized to more closely resemble controls in one of
these pathways. Patients with far removed injury (>10 years poststroke; n = 3)
did not show behavioral improvement and, despite similarities to the normative
model and overall network heterogeneity, reorganized to be less similar to
controls following therapy in a distinct right-lateralized pathway. Behavioral
improvement following aphasia therapy was associated with connectivity more
closely approximating that of healthy controls. Individuals who had a stroke more
than a decade before testing also showed plasticity, with a few pathways becoming
less like controls, possibly representing compensation. Better understanding of
these mechanisms may help direct targeted brain stimulation.
PMID- 29338312
TI - Assessment of Parental Acceptability and Preference for Behavioral Interventions
for Feeding Problems.
AB - The present study evaluates the treatment acceptability and preference for
behavioral interventions for feeding problems with parents of children with
Autism Spectrum Disorder and other developmental disabilities. The impact of
behavioral severity on acceptability and preference was also evaluated by
comparing results of parents who responded with respect to a vignette of a child
with food refusal with those who responded to a vignette of a child with food
selectivity. Overall, parents rated differential reinforcement of alternative
behavior as the most preferred and most acceptable strategy across both food
selectivity and food refusal groups. Escape extinction was the least acceptable
and least preferred across both groups, and the severity of the behavior had no
impact on acceptability or preference scores. Implications for future research on
the social validity of feeding interventions are provided.
PMID- 29338313
TI - Rapport Building and Instructional Fading Prior to Discrete Trial Instruction:
Moving From Child-Led Play to Intensive Teaching.
AB - Discrete trial instruction (DTI) is effective for teaching skills to children
with autism spectrum disorder (ASD). Although effective, instructional settings
can become aversive resulting in avoidant and escape-related behaviors. Given the
significant social impairments associated with ASD, interventions that promote
social approach and reduce avoidance are warranted. Rapport building or "pairing"
the therapist and teaching setting with highly preferred activities prior to
instruction can reduce problematic behaviors during subsequent instruction.
However, the path from child-led play to DTI is not well established.
Instructional fading may assist in bridging this gap. Four participants with ASD
who were beginning an intensive behavioral intervention program were included in
the current study. Participants progressed through nine stages of pairing and
instructional fading with minimal problem behavior and high percentages of in
seat and close proximity to the therapist. Guidelines for incorporating rapport
building strategies prior to intensive teaching with children with ASD are
proposed.
PMID- 29338314
TI - Inflammatory Cytokines in the Papillary Tips and Urine of Nephrolithiasis
Patients.
AB - INTRODUCTION: Intrarenal inflammation has been implicated in the pathogenesis of
nephrolithiasis, with prior work showing increased urine levels of IL-6, IL-8,
and CCL-2 in stone patients. However, no studies have assessed for inflammation
in the renal papillae. We sought to characterize novel papillary tip and urinary
biomarkers in stone patients. MATERIALS AND METHODS: Ninety-two patients with
nephrolithiasis undergoing percutaneous nephrolithotomy were enrolled. Papillary
tip biopsies, kidney urine, and bladder urine were collected, as well as voided
urine from eight healthy volunteers. Quantitative polymerase chain reaction was
performed to measure inflammatory gene expression. RESULTS: Initial 84-gene
polymerase chain reaction array revealed significant elevation of several
cytokines in stone patients vs controls (fold change 2.3-694). Twenty-four genes
were selected for final analysis. In 41 pairs of urine samples, levels of CCL5,
CD40, FasL, RIPK2, SELE, TLR3, and IL-15 were significantly elevated in kidney vs
bladder urine (p0.0001-0.04). In 23 triplets of samples, expression of these
cytokines plus CCL2, CCL7, CCR2, CSF1, CXCL9, and CXCL10, was significantly
greater in papillary tips vs urine samples (p0.001-0.05). Cytokine elevation was
independent of maximum postoperative heart rate, respiratory rate, temperature,
leukocyte count, urinary tract infection in the past year, presence or absence of
antibiotics at the time of surgery, and stone composition (all p > 0.05).
CONCLUSION: Expression of CCL-2, CCL-5, CCL-7, CCR-2, CD40, CSF1, CXCL-9, CXCL
10, Fas-L, RIPK2, SELE, and TLR-3 is markedly elevated in the papillary tips,
kidney urine, and bladder urine of nephrolithiasis patients. Cytokine elevation
was independent of signs of systemic inflammation. These findings further support
the role of inflammation in nephrolithiasis and imply that the inflammatory
process likely begins at the renal papillae. These may represent novel biomarkers
of stone disease, which may be useful in basic nephrolithiasis research, disease
diagnosis, and prognosis.
PMID- 29338316
TI - Retroareolar masses and intraductal abnormalities detected on screening
ultrasound: can biopsy be avoided?
AB - : To investigate the malignancy rate of retroareolar masses and intraductal
abnormalities discovered in asymptomatic females during screening whole breast
ultrasound (US-S) and determine if biopsy can be avoided. METHODS:: This is a
HIPAA compliant retrospective study. Our radiology electronic medical records
were searched for the phrases "retroareolar mass" or "intraductal mass" combined
with "screening whole breast ultrasound" performed between 10/1/2009 and
5/30/2015. Inclusion criteria included retroareolar masses in asymptomatic
females with normal mammography, mammographically dense breast tissue and imaging
or biopsy follow-up. RESULTS:: 1136 charts were reviewed. 87 BI-RADS 3 and 4
retroareolar findings were included in final analysis. The average lesion size
was 9.5 mm (range 4-28 mm). 47/87 lesions were classified as BI-RADS 3 and 40/87
BI-RADS 4. Of the 47 BI-RADS 3 lesions, 36 were stable on follow-up; 6 benign
lesions were biopsied at patients' request; and 5 biopsied due to suspicious
interval change on follow-up imaging, including 4 benign lesions and a 5 mm Grade
2 ductal carcinoma in situ . 3/40 BI-RADS 4 lesions were not biopsied and stable
at follow-up; 37/40 lesions underwent benign biopsy. The malignancy rate of BI
RADS 3 and 4 lesions was 2.1% [CI (0.4-11.1)] and 0% [CI (0.0-8.8)],
respectively. The overall combined malignancy rate was 1/87 [1.1%, CI (0.2-6.2)].
CONCLUSION:: The malignancy rate for BI-RADS 3 and 4 retroareolar masses and
intraductal abnormalities detected on US-S is low (<2%). ADVANCES IN KNOWLEDGE::
Careful imaging surveillance in lieu of biopsy of these lesions may be
appropriate in asymptomatic females with negative mammography.
PMID- 29338317
TI - Cosmos, gods and madmen: frameworks in the anthropologies of medicine, edited by
Roland Littlewood and Rebecca Lynch.
PMID- 29338315
TI - The chronic ischaemic cardiovascular disease ESC Pilot Registry: Results of the
six-month follow-up.
AB - Aim Chronic ischaemic cardiovascular disease (CICD) remains a leading cause of
morbidity and mortality worldwide. The CICD Pilot Registry enrolled 2420 patients
across 10 European Society of Cardiology countries prospectively to describe
characteristics, management strategies and clinical outcomes in this setting. We
report here the six-month outcomes. Methods and results From the overall
population, 2203 patients were analysed at six months. Fifty-eight patients
(2.6%) died after inclusion; 522 patients (23.7%) experienced all-cause
hospitalisation or death. The rate of prescription of angiotensin-converting
enzyme inhibitors, beta-blockers and aspirin was mildly decreased at six months
(all P < 0.02). Patients who experienced all-cause hospitalisation or death were
older, more often had a history of non-ST-segment elevation myocardial
infarction, of chronic kidney disease, peripheral revascularisation and/or
chronic obstructive pulmonary disease than those without events. Independent
predictors of all-cause mortality/hospitalisation were age (hazard ratio (HR)
1.17, 95% confidence interval (CI) 1.07-1.27) per 10 years, and a history of
previous peripheral revascularisation (HR 1.45, 95% CI 1.03-2.03), chronic kidney
disease (HR 1.31, 95% CI 1.0-1.68) or chronic obstructive pulmonary disease (HR
1.42, 95% CI 1.06-1.91, all P < 0.05). We observed a higher rate of events in
eastern, western and northern countries compared to southern countries and in
cohort 1. Conclusion In this contemporary European registry of CICD patients, the
rate of severe clinical outcomes at six months was high and was influenced by
age, heart rate and comorbidities. The medical management of this condition
remains suboptimal, emphasising the need for larger registries with long-term
follow-up. Ad-hoc programmes aimed at implementing guidelines adherence and
follow-up procedures are necessary, in order to improve quality of care and
patient outcomes.
PMID- 29338318
TI - Perceptions of patient-provider communication and receipt of mental health
treatment among older adults with depressive symptoms.
AB - OBJECTIVES: This study aimed to: (1) determine if and how perceptions towards
healthcare providers differ between older adults with and without clinically
signifcant depressive symptoms (CSDS), and (2) assess whether perceptions towards
providers are associated with receipt of mental health treatment among older
adults with CSDS. METHODS: Data from the 2013 and 2014 Medical Expenditure Panel
Survey were used to examine CSDS prevalence, receipt of mental health treatment,
and perceptions of provider communication among community-dwelling adults >= age
65 (N = 6,936) using four of the 'How Well Doctors Communicate' composite items
from the Consumer Assessment of Healthcare Providers and Systems(CAHPS).
Multivariate logistic regression was used. RESULTS: CSDS are associated with
greater odds of having 'poor' perceptions of provider communication on all four
CAHPS communication measures. Perceptions of provider communication are similar
among older adults with CSDS who received and did not receive mental health
treatment, except on an item measuring a provider's ability to explain
information in ways patients understand. CONCLUSION: Older adults with CSDS have
more negative perceptions of the quality of their communication with healthcare
providers than their peers. Healthcare systems should consider how to accommodate
these patients' unique needs and communication preferences to ensure receipt of
quality care.
PMID- 29338320
TI - Effect of a group medical clinic for veterans with diabetes on body mass index.
AB - Objective To assess the impact of a group medical clinic designed for patient
with type 2 diabetes mellitus and hypertension on body mass index. Methods Using
data from a randomized trial of 239 veterans with type 2 diabetes mellitus, we
performed a secondary analysis using analysis of covariance mixed models to
explore the effect of a 12-month group medical clinic intervention on change in
body mass index vs. usual care. In an exploratory subgroup analysis, we compared
change in body mass index between treatment arms stratified by whether patients
had >0.5% reduction in hemoglobin A1c at 12 months. Results Baseline body mass
index was 33.5 kg/m2. At 12 months, there was no significant difference in change
in body mass index between treatment arms (estimate=-0.02, 95% CI -0.51 to 5.05;
P = 0.94); body mass index increased by approximately 0.20 points in both groups.
There was also no significant difference in change in body mass index between
treatment arms by whether or not patients had >0.5% reduction in hemoglobin A1c
(estimate=-0.14, 95% CI -1.21 to -0.92; P = 0.79). Discussion Improved glycemic
control was not associated with improved body mass index in the group medical
clinic intervention. Given their positive effects on other outcomes, group
medical clinics for patients with type 2 diabetes mellitus may be more beneficial
if focus is shifted towards weight loss.
PMID- 29338319
TI - Clinical evaluation of circulating miR-548a-3p and -20a expression in malignant
pleural mesothelioma patients.
AB - AIM: miRNAs may act as promising diagnostic and prognostic biomarkers of
mesothelioma. This study integrates serum miR-548a-3p and miR-20a expression
based on in silico data analysis followed by clinical validation in malignant
mesothelioma patients (malignant pleural mesothelioma [MPM]). PATIENTS & METHODS:
Serum miR-548a-3p and miR-20a level was assessed in the serum of patients with
MPM, chronic asbestos exposure and healthy volunteers by quantitative real-time
PCR. RESULTS: The expression of serum miR-548a-3p and miR-20a was positive in
91.6 and 96.7% MPM patients, respectively. Both miRNAs were able to segregate
between cases and controls. The sensitivity of the combined chosen serum miRNAs
reached 100% in the diagnosis of MPM. CONCLUSION: The current work revealed that
sera miR-548a-3p and miR-20a may serve as promising novel diagnostic tools for
MPM.
PMID- 29338321
TI - Are wishes for death or suicidal ideation symptoms of depression in older adults?
AB - OBJECTIVE: Clinicians may question whether thoughts of being better off dead are
normal consequences of aging or symptoms of depression. We examine whether
thoughts of suicide are as strongly linked to depression severity in older adults
as they are in other age groups. METHODS: Cross-sectional cohort study.
Participants included 509,945 outpatients >18 years old from four large
integrated healthcare systems in the Mental Health Research Network who completed
1.2 million Patient Health Questionnaires (PHQ) and had data to calculate
Charlson Comorbidity Index scores from 2010 through 2012. The PHQ8 estimated
depression severity, while suicidal ideation was measured using the 9th item of
the PHQ. Data were abstracted from a Virtual Data Warehouse. RESULTS: In older
adult patients, suicidal ideation was strongly associated with depression
severity. Older adults who had at least moderately-severe depression (PHQ8 >=15)
were 48 times more likely (95% CI: 42.8-53.8) to report suicidal ideation than
those with minimal or mild symptoms of depression (PHQ8 <10) after adjustment for
all other variables in the model, including medical comorbidity burden.
CONCLUSIONS: Depression severity was by far the strongest predictor of suicidal
ideation in older adult patients. Older patients with suicidal ideation should be
screened for depression.
PMID- 29338322
TI - Associations of mindfulness with depressive symptoms and well-being in older
adults: the moderating role of neuroticism.
AB - OBJECTIVE: To investigate whether observed interactions of mindfulness with the
personality trait neuroticism extend to older adults and to aspects of
psychological functioning other than depressive symptoms, and whether effects of
mindfulness training in this population depend on levels of neuroticism. METHOD:
We performed a secondary analysis of data from a randomized controlled trial of
Mindfulness-Based Stress Reduction (MBSR) for community-dwelling older adults. We
investigated whether neuroticism moderates associations of dispositional
mindfulness with various aspects of psychological and physical functioning at
baseline, as well as effects of MBSR on these outcomes. RESULTS: Significant two
way interactions showed that greater mindfulness was associated with fewer
depressive symptoms and less negative affect at baseline in individuals with
average or higher levels of neuroticism. In contrast, mindfulness was associated
with greater positive affect and vitality and fewer physical symptoms regardless
of the level of neuroticism. There were no effects of MBSR on these outcomes at
any level of neuroticism. CONCLUSION: Mindfulness may be more protective against
psychological ill-being in older adults with higher levels of neuroticism, but
conducive to positive psychological and physical well-being regardless of this
personality trait. The potential moderating role of neuroticism should be further
evaluated in studies of mindfulness-based interventions in older adults.
PMID- 29338323
TI - Psychosocial interventions for people with dementia: a synthesis of systematic
reviews.
AB - OBJECTIVES: Over the last 10 years there has been a multitude of studies of
psychosocial interventions for people with dementia. However, clinical services
face a dilemma about which intervention should be introduced into clinical
practice because of the inconsistency in some of the findings between different
studies and the differences in the study qualities and trustworthiness of
evidence. There was a need to provide a comprehensive summary of the best
evidence to illustrate what works. METHODS: A review of the systematic reviews of
psychosocial interventions in dementia published between January 2010 and
February 2016 was conducted. RESULTS: Twenty-two reviews (8 physical, 7
cognitive, 1 physical/cognitive and 6 other psychosocial interventions) with a
total of 197 unique studies met the inclusion criteria. Both medium to longer
term multi-component exercise of moderate to high intensity, and, group cognitive
stimulation consistently show benefits. There is not sufficient evidence to
determine whether psychological or social interventions might improve either mood
or behaviour due to the heterogeneity of the studies and interventions included
in the reviews. CONCLUSION: There is good evidence that multi-component exercise
with sufficient intensity improves global physical and cognitive functions and
activities of daily living skills. There is also good evidence that group-based
cognitive stimulation improves cognitive functions, social interaction and
quality of life. This synthesis also highlights the potential importance of group
activities to improve social integration for people with dementia. Future
research should investigate longer-term specific outcomes, consider the severity
and types of dementia, and investigate mechanisms of change.
PMID- 29338324
TI - Effect of Vertical or Beveled Chondral Defect Creation on Rim Deformation and
Contact.
AB - Objective To determine biomechanical effects of knee cartilage defect perimeter
morphology based on cartilage strain and opposing subchondral bone contact.
Design Articular cartilage defects were created in 5 bovine femoral condyles:
group 1, 45 degrees inner bevel with 8-mm rim; group 2, vertical with 8-mm rim;
and group 3, 45 degrees outer bevel with 8-mm base. Samples were placed into a
custom-machined micro-computed tomography tube and subjected to 800 N of axial
loading. DICOM data were used to calculate cartilage thickness 4 and 6 mm from
the center, distance between tibial cartilage surface and femoral subchondral
bone, and contact width between tibial cartilage and subchondral bone. Strain 4
mm from the center and both absolute and change in distance (mm) to subchondral
bone were compared between groups 1 and 2 using paired t tests. Strain at 6 mm
and distance changed, loaded distance, and contact width (mm) were compared
between groups using the Friedman test with post hoc analysis using Wilcoxon
signed rank test. Results No significant differences in rim strain were noted
between groups 1 and 2 at 4 mm ( P = 0.10) and between groups 1, 2, and 3 at 6 mm
( P = 0.247) from the defect center. The loaded distance was significantly
different between groups 1 and 3 ( P = 0.013). No significant change in distance
to the subchondral bone was found between groups ( P = 0.156). The difference in
subchondral bone contact area approached but did not reach significance ( P =
0.074). Conclusion When debriding focal articular cartilage defects,
establishment of an inner bevel decreases tissue deformation and contact with
opposing subchondral bone.
PMID- 29338325
TI - Comparative Evaluations of Randomly Selected Four Point-of-Care Glucometer
Devices in Addis Ababa, Ethiopia.
AB - BACKGROUND: Point-of-care glucometer (PoCG) devices play a significant role in
self-monitoring of the blood sugar level, particularly in the follow-up of high
blood sugar therapeutic response. The aim of this study was to evaluate blood
glucose test results performed with four randomly selected glucometers on
diabetes and control subjects versus standard wet chemistry (hexokinase) methods
in Addis Ababa, Ethiopia. METHOD: A prospective cross-sectional study was
conducted on randomly selected 200 study participants (100 participants with
diabetes and 100 healthy controls). Four randomly selected PoCG devices (CareSens
N, DIAVUE Prudential, On Call Extra, i-QARE DS-W) were evaluated against
hexokinase method and ISO 15197:2003 and ISO 15197:2013 standards. RESULTS: The
minimum and maximum blood sugar values were recorded by CareSens N (21 mg/dl) and
hexokinase method (498.8 mg/dl), respectively. The mean sugar values of all PoCG
devices except On Call Extra showed significant differences compared with the
reference hexokinase method. Meanwhile, all four PoCG devices had strong positive
relationship (>80%) with the reference method (hexokinase). On the other hand,
none of the four PoCG devices fulfilled the minimum accuracy measurement set by
ISO 15197:2003 and ISO 15197:2013 standards. In addition, the linear regression
analysis revealed that all four selected PoCG overestimated the glucose
concentrations. CONCLUSIONS: The overall evaluation of the selected four PoCG
measurements were poorly correlated with standard reference method. Therefore,
before introducing PoCG devices to the market, there should be a standardized
evaluation platform for validation. Further similar large-scale studies on other
PoCG devices also need to be undertaken.
PMID- 29338326
TI - Diabetes mellitus and atrial remodelling in patients with paroxysmal atrial
fibrillation: Role of electroanatomical mapping and catheter ablation.
AB - Complex fractionated atrial electrograms (CFAEs) are related to atrial fibrosis,
but their ablation has not yet shown superiority. The aim of the study was to
compare, in terms of clinical outcome, two strategies of paroxysmal atrial
fibrillation (AF) ablation in patients with type 1 diabetes mellitus (DM):
pulmonary vein isolation (PVI) vs. PVI + CFAEs. Compared to an historical
population of patient with paroxysmal AF and without DM, a higher percentage of
patients with DM showed more than 25% of atrial area interested by CFAEs (study
population, 58% vs historical group, 15%; p < 0.05). In PVI group, recurrences
rate was similar in patients with HbA1c ? 7.5% vs HbA1c > 7.5% (30% vs 22%; p =
not significant), but a greater AF burden was observed in patients with HbA1c >
7.5% (6 +/- 2 vs 1 +/- 2; p < 0.05). In hazard ratios analysis PVI+CFAEs seems
more effective than PVI alone in patients with HbA1c > 7.5% (hazard ratio, 1.28;
p < 0.05), more than 25 years from DM diagnosis (hazard ratio, 1.25; p < 0.05)
and more than five AF episodes/year (hazard ratio, 1.2; p < 0.05). Type 1 DM
patients had complex atrial 'substrate', as documented by wider CFAEs areas.
Despite this, 1-year follow-up recurrence rate was similar between two ablation
approaches (PVI 27% vs. PVI+CFAEs 21%; p = not significant). In our study, only
specific subgroups, like patients with disglycaemic state (HbA1c > 7.5%), long
diabetes mellitus history and high AF burden, benefit from PVI+ CFAEs approach.
PMID- 29338327
TI - Respiratory-gated PET/CT for pulmonary lesion characterisation-promises and
problems.
AB - 2-deoxy-2-(18Fluorine)-fluoro-D-glucose (FDG) PET/CT is an integral part of lung
carcinoma staging and frequently used in the assessment of solitary pulmonary
nodules. However, a limitation of conventional three-dimensional PET/CT when
imaging the thorax is its susceptibility to motion artefact, which blurs the
signal from the lesion resulting in inaccurate representation of size and
metabolic activity. Respiratory gated (four-dimensional) PET/CT aims to negate
the effects of motion artefact and provide a more accurate interpretation of
pulmonary nodules and lymphadenopathy. There have been recent advances in
technology and a shift from traditional hardware to more streamlined software
methods for respiratory gating which should allow more widespread use of
respiratory-gating in the future. The purpose of this article is to review the
evidence surrounding four-dimensional PET/CT in pulmonary lesion
characterisation.
PMID- 29338328
TI - Avoidance, meaning and grief: psychosocial factors influencing engagement in HIV
care.
AB - Although the introduction of antiretroviral therapy has rendered HIV a chronic
illness, inconsistent engagement in HIV care by key populations limits its public
health impact. Poor engagement in care is especially prevalent among vulnerable
populations with mental health and substance use disorders. Beyond structural and
health system considerations, psychosocial factors may present challenges to
sustained engagement. We conducted a qualitative study using in-depth interviews
with 31 primarily African American, urban-based individuals, many with past or
current drug use and mental disorders, living with HIV. Participants identified
several psychosocial barriers that detract from their motivation to attend
appointments and take medication. These included mental distress or detachment
over a lack of purpose in life; denial about the need to be engaged in care;
insufficient trust in the efficacy of care or the health system; deaths of loved
ones leading to bereavement or loss of social support; and engagement in specific
avoidance behaviors like drugs and alcohol. The study findings suggest that more
comprehensive HIV care, which integrates mental health and substance abuse
services in order to enhance meaning and address coping and grief, may be
important. Considering these services in addition to improving the logistical
components of care such as cues/reminders, accessibility, and patient-provider
communication may improve intervention packages.
PMID- 29338329
TI - Making a university community more dementia friendly through participation in an
intergenerational choir.
AB - A dementia friendly community is one that is informed about dementia, respectful
and inclusive of people with dementia and their families, provides support,
promotes empowerment, and fosters quality of life. This study presents data from
four cohorts of undergraduate college students and people with dementia and their
family members, using an intergenerational choir as the process through which to
begin to create a dementia friendly community. This was accomplished by breaking
down the stereotypes and misunderstandings that young adults have about people
with dementia, thus allowing their commonalities and the strengths of the people
living with dementia to become more visible. Data were gathered for each cohort
of students through semi-structured open-ended questions on attitudes about
dementia and experiences in the choir, collected at three points over 10 weeks of
rehearsals. Data about their experiences in the choir were collected from each
cohort of people with dementia and their family members through a focus group.
Results across all four cohorts showed in the students: changed attitudes,
increased understanding about dementia and the lived experience, reduced dementia
stigma, and the development of meaningful social connections. People with
dementia and their family members expressed feelings of being part of a
community.
PMID- 29338330
TI - Joint Influence of SNPs and DNA Methylation on Lipids in African Americans From
Hypertensive Sibships.
AB - INTRODUCTION: Plasma concentrations of lipids (i.e., total cholesterol, high
density cholesterol, low-density cholesterol, and triglycerides) are amenable to
therapeutic intervention and remain important factors for assessing risk of
cardiovascular diseases. Some of the observed variability in serum lipid
concentrations has been associated with genetic and epigenetic variants among
cohorts with European ancestry (EA). Serum lipid levels have also been associated
with genetic variants in multiethnic populations. METHODS: The purpose of this
study was to determine whether single-nucleotide polymorphisms (SNPs) and DNA
methylation (DNAm) differences contribute to lipid variation among African
Americans ([AAs], N = 739) in the Genetic Epidemiology Network of Arteriopathy
(GENOA) study. RESULTS: Previous meta-analyses identified 161 SNPs that are
associated with lipid traits in populations of EA. We evaluated these SNPs and 66
DNAm sites within the genes containing the SNPs in the GENOA cohort using linear
mixed-effects modeling. We did not identify any significant associations of SNPs
or DNAm with serum lipid levels. These results suggest that the SNPs identified
as being significant for lipid levels through the EA genome-wide association
studies may not be significant across AA populations. CONCLUSIONS: Reductions in
morbidity and mortality due to variation in lipids among AAs may be achieved
through a better understanding of the genetic and epigenetic factors associated
with serum lipid levels for early and appropriate screening. Further large-scale
studies specifically within AA and other non-EA populations are warranted.
PMID- 29338331
TI - The impact of HIV diagnosis on length of hospital stay in New York City, NY, USA.
AB - While hospitalizations among people living with human immunodeficiency virus
(PLWH) have been elevated in the past compared to their uninfected counterparts,
the introduction of antiretroviral therapy (ART) has resulted in great strides in
controlling symptomatic infection. However, research largely overlooks important
differences among HIV-infected individuals, primarily PLWH who are symptomatic
versus those who are asymptomatic. We conducted a retrospective study assessing
the length of hospital stay among 717,237 admissions from three hospitals in the
New York City area. Using zero-truncated negative binomial regression we
documented trends in length of hospital stay among individuals who are HIV
positive (with symptoms versus those without symptoms) compared to HIV-negative
patients over nine consecutive years, from 2006 to 2014. Approximately 0.85% of
the admissions were infected with asymptomatic HIV (n = 6,131), while 1.43% of
admissions were infected with symptomatic HIV (n = 10,271). The length of stay
(LOS) among symptomatic HIV-infected admissions was 32.0% (95% CI: 29.7%-34.2%)
longer than LOS in the general admissions. The mean LOS dropped about 1.5% (95%
CI: 1.5%-1.6%) per year in the study sample. The LOS in inpatients with
asymptomatic HIV had the same LOS as the general inpatient population. Our
findings highlight the need for comprehensive strategies to reduce length of
hospitalization among HIV-infected individuals.
PMID- 29338332
TI - Venous Thromboembolism in Podiatric Foot and Ankle Surgery.
AB - BACKGROUND: The extent to which podiatric surgeons follow venous thromboembolism
guidelines is unknown. The aim of this study therefore, was 2-fold: (a) to
determine the rate of venous thromboembolism following podiatric surgery and (b)
to investigate the factors that influence the use of thromboprophylaxis. METHODS:
Data from 4238 patients who underwent foot and ankle surgery over 2 years were
analyzed. Venous thromboembolism within the first 30 days following surgery was
recorded using the Australasian College of Podiatric Surgeons surgical audit
tool. Logistic regression analyses were undertaken to determine the factors that
influenced thromboprophylaxis. RESULTS: Of the 4238 patient records, 3677 records
(87%) provided complete data (age range 2-94 years; mean +/- SD, 49.1 +/- 19.7
years; 2693 females). A total of 7 venous thromboembolic events (0.2% rate) were
reported. Operative duration and age (OR 12.63, 95% CI 9.47 to 16.84, P < 0.01),
postoperative immobilization (OR 6.94, 95% CI 3.95 to 12.20, P < 0.01), and a
prior history of VTE (OR 3.41, 95% CI 1.01 to 11.04, P = 0.04) were the strongest
predictors of thromboprophylaxis. CONCLUSION: Podiatric foot and ankle surgery is
associated with a low rate of venous thromboembolism. This may be due in part to
the thromboprophylaxis regime implemented by podiatric surgeons, which closely
aligns with current evidence-based guidelines. LEVELS OF EVIDENCE: Level II:
Prospective cohort study.
PMID- 29338333
TI - Endoscopic Transfer of Flexor Hallucis Longus Tendon for Chronic Achilles Tendon
Rupture: Technical Aspects and Short-Time Experiences.
AB - BACKGROUND: Chronic Achilles tendon ruptures can lead to reduced power of plantar
flexion in the ankle with impaired gait ability. The open 1- or 2-incision
technique for flexor hallucis longus transfer has proven good functional outcome
but has the disadvantage of relatively extensive surgery performed at a
vulnerable location. To reduce the risk of soft tissue problems, the flexor
hallucis longus transfer can be performed endoscopically. MATERIAL AND METHOD: An
endoscopic technique for flexor hallucis longus transfer is presented together
with the experiences from the first six patients operated with this method.
RESULTS: No wound healing problems or infections. Five of 6 patients managed
single leg heel raise on the affected side 12 months after surgery. CONCLUSION:
The functional results are promising. The soft tissue dissection is minor, and no
patients had postoperative wound healing problems or infection. Endoscopic flexor
hallucis longus transfer may be an operative procedure that can be considered
also in patients with potential wound healing problems. LEVELS OF EVIDENCE: Level
IV: Technical note/case series without controls.
PMID- 29338334
TI - Proximal to Distal Exostectomy for the Treatment of Insertional Achilles
Tendinopathy.
AB - : When insertional Achilles tendinopathy is addressed surgically via a central
Achilles splitting approach, the calcaneal osteotomy has classically been
performed from distal to proximal. We describe a simple proximal to distal
technique that allows optimal resection of both the calcaneal exostosis and
Achilles enthesophyte, minimizes risk to the soft tissues and skin, provides a
bony attachment surface parallel to the axis of the Achilles tendon, and avoids
the risk of osteotomy extension into the subtalar joint. LEVELS OF EVIDENCE:
Level V: Technique tip.
PMID- 29338335
TI - Diabetic Retinopathy and the Cascade into Vision Loss.
AB - Vision loss from diabetic retinopathy should be unnecessary for patients with
access to diabetic retinopathy screening, yet it still occurs at high rates and
in varied contexts. Precisely because vision loss is only one of many late-stage
complications of diabetes, interfering with the management of diabetes and making
self-care more difficult, Vision Threatening Diabetic Retinopathy (VTDR) is
considered a "high stakes" diagnosis. Our mixed-methods research addressed the
contexts of care and treatment seeking in a sample of people with VTDR using
safety-net clinic services and eye specialist referrals. We point to conceptual
weaknesses in the single disease framework of health care by diagnosis, and we
use the framework of "cascades" to clarify why and how certain non-clinical
factors come to bear on long-term experiences of complex chronic diseases.
PMID- 29338336
TI - Changes in microbial growth, carotenoids, and water-soluble tannin content of
ripe persimmon beverage after ultra-high pressure treatment.
AB - To avoid the loss of carotenoids and increasing the tannin content associated
with pasteurization, we tested ultra-high pressure treatment of ripe persimmon
beverage. We compared microbial counts (aerobic bacteria, coliforms, and mould),
carotenoid contents, and water-soluble tannin contents between heat- and ultra
high pressure-treated beverages. No microbial contamination was detected after
pasteurization or ultra-high pressure treatment at 400 MPa for more than 5 min.
Ultra-high pressure treatment significantly prevented the reduction in
carotenoids (lutein, zeaxanthin, beta-cryptoxanthin, beta-carotene, lycopene),
with losses of 3.9-28.7%, as compared to the 65% loss after pasteurization.
Moreover, ultra-high pressure did not induce an increase in water-soluble tannin,
which causes astringent taste, whereas water-soluble tannins were increased three
times by heat treatment. In conclusion, ultra-high pressure showed the same
microbial control effect as pasteurization, while it did not cause carotenoid
degeneration and increased tannin and thus, it better maintained the quality of
ripe persimmon beverage.
PMID- 29338337
TI - Significance of combined preoperative serum Alb and dNLR for diagnosis of
pancreatic cancer.
AB - AIM: To investigate diagnostic value of preoperative inflammatory biomarkers in
pancreatic cancer (PCC). MATERIALS & METHODS: Preoperative circulating Alb/Fib
ratio, neutrophil/lymphocyte ratio (NLR), derived NLR (dNLR), platelet/lymphocyte
ratio and lymphocyte/monocyte ratio were detected and calculated in 226 PCC
individuals, 232 healthy controls and 142 additional cancer controls. Receiver
operating characteristic curve and area under the curve (AUC) were used to
evaluate the diagnostic efficacy of PCC. RESULTS: Combined circulating dNLR and
Alb could effectively improve the diagnosis of PCC (AUC = 0.931), single dNLR
could distinguish early-stage PCC and the disease from healthy controls (AUC =
0.895) and additional cancer controls (AUC = 0.794). CONCLUSION: Circulating dNLR
was an effective biomarker for diagnosis and identification of early-stage PCC.
Combined dNLR and Alb could improve the diagnostic efficacy of the disease.
PMID- 29338339
TI - Some Management Information Issues in Indigenous Health.
PMID- 29338338
TI - Sesbagrandiflorain A and B: isolation of two new 2-arylbenzofurans from the stem
bark of Sesbania grandiflora.
AB - Native to tropical Asia, Sesbania grandiflora (L.), Pers is a member of the
Fabaceae family of flowering plants. All parts of S. grandiflora are used in
traditional medicine and phytochemical investigations have been conducted on
extracts of the leaves, seeds and roots of S. grandiflora to provide scientific
validation of its properties. However, to date, no study has determined the
phytochemical constituents of S. grandiflora stem bark. The stem bark powdered of
S. grandiflora was extracted exhaustively with n-hexane, EtOAc and 90% aqueous
MeOH sequentially. In this study, we successfully isolated two new 2
arylbenzofurans, sesbagrandiflorain A and B, from the EtOAc stem bark of S.
grandiflora. The structure elucidation of these compounds was determined by using
one- and two-dimensional nuclear magnetic resonance, ultraviolet and infrared
spectroscopy and electrospray ionisation time-of-flight mass spectrometry. The
finding expands the understanding of the natural constituents of the Fabaceae
and, in particular, the Papilionoideae genera.
PMID- 29338340
TI - The ICD-10-AM Mental Health Manual: An Integrated Classification and Diagnostic
Tool for Community-Based Mental Health Services.
PMID- 29338342
TI - President's Report.
PMID- 29338341
TI - RNA sequencing on Amomum villosum Lour. induced by MeJA identifies the genes of
WRKY and terpene synthases involved in terpene biosynthesis.
AB - Amomum villosum Lour. is an important Chinese medicinal plant that has diverse
medicinal functions, and mainly contains volatile terpenes. This study aims to
explore the WRKY transcription factors (TFs) and terpene synthase (TPS) unigenes
that might be involved in terpene biosynthesis in A. villosum, and thus providing
some new information on the regulation of terpenes in plants. RNA sequencing of
A. villosum induced by methyl jasmonate (MeJA) revealed that the WRKY family was
the second largest TF family in the transcriptome. Thirty-six complete WRKY
domain sequences were expressed in response to MeJA. Further, six WRKY unigenes
were highly correlated with eight deduced TPS unigenes. Ultimately, we combined
the terpene abundance with the expression of candidate WRKY TFs and TPS unigenes
to presume a possible model wherein AvWRKY61, AvWRKY28, and AvWRKY40 might
coordinately trans-activate the AvNeoD promoter. We propose an approach to
further investigate TF unigenes that might be involved in terpenoid biosynthesis,
and identified four unigenes for further analyses.
PMID- 29338343
TI - Molecular analysis of anthocyanin biosynthesis pathway genes and their
differential expression in mango peel.
AB - Mango fruit is cherished by masses for its taste and nutrition, contributed by
color, flavor, and aroma. Among these, peel color is an important trait
contributing to fruit quality and market value. We attempted to elucidate the
role of key genes of the anthocyanin biosynthesis pathway related to fruit peel
color from the leaf transcriptome of mango cultivar Amrapali. A total of 108
mined transcript sequences were assigned to the phenylpropanoid-flavonoid pathway
from which 15 contigs representing anthocyanin biosynthesis genes were annotated.
Alternate splice variants were identified by mapping against genes of Citrus
clementina and Vitis vinifera (closest relatives) and protein subcellular
localization was determined. Phylogenetic analysis of these pathway genes
clustered them into distinct groups aligning with homologous genes of Magnifera
indica, C. clementina, and V. vinifera. Expression profiling revealed higher
relative fold expressions in mature fruit peel of red-colored varieties (Arunika,
Ambika, and Tommy Atkins) in comparison with the green-peeled Amrapali. MiCHS,
MiCHI, and MiF3H alternate splice variants revealed differential gene expression.
Functionally divergent variants indicate availability of an allelic pool
programmed to play critical roles in peel color. This study provides insight into
the molecular genetic basis of peel color and offers scope for development of
biomarkers in varietal improvement programs.
PMID- 29338345
TI - Effect of Anacardium occidentale leaf extract on human acute lymphoblastic
leukaemia cell lines.
AB - Anacardium occidentale leaves are used in folk medicine due its therapeutic
properties attributed to phenolic compounds. Therefore, this study was undertaken
on its hydroethanolic leaf extract (AoHE) to evaluate cytotoxicity and apoptosis
induction on acute lymphoblastic leukaemia cells. Results indicated that AoHE
interfered in the cell cycle progression, inducing apoptosis by activation of
casp3 at lower concentrations, thence, a promising candidate for the development
of new cancer drugs.
PMID- 29338344
TI - Reappraisal inventiveness: impact of appropriate brain activation during efforts
to generate alternative appraisals on the perception of chronic stress in women.
AB - BACKGROUND AND OBJECTIVES: Previous research indicated that more left-lateralized
prefrontal activation during cognitive reappraisal efforts was linked to a
greater capacity for generating reappraisals, which is a prerequisite for the
effective implementation of cognitive reappraisal in everyday life. The present
study examined whether the supposedly appropriate brain activation is relevant in
terms of more distal outcomes, i.e., chronic stress perception. DESIGN AND
METHODS: Prefrontal EEG alpha asymmetry was recorded while female participants
were generating reappraisals for stressful events and was correlated with their
self-reported chronic stress levels in everyday life (n = 80). RESULTS: Women
showing less left-lateralized brain activity in the ventrolateral prefrontal
cortex during cognitive reappraisal efforts reported experiencing more stress in
their daily lives. This effect was independent of self-efficacy beliefs in
managing negative emotions. CONCLUSION: These findings underline the practical
relevance of individual differences in appropriate brain activation during
emotion regulation efforts and the assumedly related basic capacity for the
generation of cognitive reappraisals to the feeling of being stressed.
Implications include the selection of interventions for the improvement of coping
with stress in women in whom the capability for appropriate brain activation
during reappraisal efforts may be impaired, e.g., due to depression or old age.
PMID- 29338346
TI - Foot Mobility Magnitude and Stiffness in Children With and Without Calcaneal
Apophysitis.
AB - BACKGROUND: This study evaluated quasi-static measures of foot mobility magnitude
(FMM) and foot stiffness (FS) in children, aged 8 to 14 years, with and without
calcaneal apophysitis. METHODS: Between 2016 and 2017, FMM and FS measurements
were captured on 41 children (22 cases and 19 controls) using a custom-built foot
assessment platform. The platform incorporated a portable force plate that
allowed quantification of vertical force during double-limb stance (DLS).
RESULTS: There was no significant difference in FS in children with and without
calcaneal apophysitis ( P = .459). FMM was significantly greater (+19%) in
children with calcaneal apophysitis than in those without ( P = .045). The mean
difference in FMM between groups (1.4 mm), however, did not exceed the minimum
detectable change at the 95% confidence level (MDC95%) for the measurement (+/
2.5 mm). CONCLUSION: Differences in FMM in children with calcaneal apophysitis
were small and within the observed error of measurement. Clinical measures of FS
did not differ in children with and without calcaneal apophysitis during
quasistatic loading. Further research evaluating the level of uncertainty of the
measurement techniques in children and under dynamic loading conditions is
recommended. These findings question the rationale behind interventions which aim
to modify quasistatic foot mobility and stiffness in children with calcaneal
apophysitis. LEVEL OF EVIDENCE: Level III, comparative series.
PMID- 29338347
TI - Developments and Issues in ePrescribing and eHealth.
PMID- 29338348
TI - Links to Cyber Health: Government Web Sites, Australia.
PMID- 29338349
TI - A multistep docking and scoring protocol for congeneric series: Implementation on
kinase DFG-out type II inhibitors.
AB - AIM: Rescoring of docking-binding poses can significantly improve molecular
docking results. Our aim was to evaluate postprocessing docking protocols in
order to determine the most suitable methodology for the study of the binding of
congeneric compounds to protein kinases. MATERIALS & METHODS: Diverse ligand
receptor poses generated after docking were submitted to different relaxation
protocols. The Molecular Mechanics Poisson-Boltzmann (Generalized Born) Surface
Area approach was applied for the evaluation of the binding affinity of complexes
obtained. The performance of various Molecular Mechanics Poisson-Boltzmann
(Generalized Born) Surface Area methodologies was compared. RESULTS: The
inclusion of a postprocessing protocol after docking enhances the quality of the
results, although the best methodology is system dependent. CONCLUSION: An
examination of the interactions established has allowed us to suggest useful
modifications for the design of new type II inhibitors.
PMID- 29338350
TI - Polyketides from the fungus Penicillium decumbens.
AB - Two new polyketides, 3,11-dihydroxy-6,8-dimethyldodecanoic acid (1) and
trichopyrone B (2), together with two known polyketides, sorbicillin (3) and
penicillone A (4), have been isolated from the cultures broth of the fungus
Penicillium decumbens. Their structures were elucidated by extensive
spectroscopic analysis. All isolated compounds were evaluated for their
antibacterial and cytotoxic activities. Of these, compound 3 showed antifungal
activity toward Candida albicans Y0109 with a MIC value of 50 MUM. Moreover,
compounds 3 and 4 exhibited selective cytotoxicity against the human
hepatocellular carcinoma (QGY-7703) cell line with the IC50 values of 32.5 and
22.8 MUM, respectively.
PMID- 29338351
TI - A new lindenane-type sesquiterpenoid lactone from Chloranthus japonicus.
AB - Chromatographic fractionation of the EtOH extracts of the Traditional Chinese
Medicine (TCM) Chloranthus japonicus, has led to the isolation of a new lindenane
type sesquiterpenoid lactone derivative (1). Rosmarylchloranthalactone E (1),
which consists of lindenane sesquiterpenoid lactone and rosmarinic acid moieties
linked via an ester bridge, was structurally elucidated by 1D and 2D NMR and HRMS
data. Compound 1 was a potent phosphodiesterase-4 (PDE4) inhibitor with an IC50
value of 0.96 +/- 0.04 MUM.
PMID- 29338352
TI - Anti-inflammatory and antioxidant activities of Rungia congoensis, a traditional
vegetable consumed by Yombe people from Kongo Central area (DR. Congo).
AB - Rungia congoensis, a traditional vegetable from Kongo Central area (DR. Congo)
was studied for establishing microscopic characters and characterised by
chromatographic techniques and their in vitro biochemical activities against ROS
production were evaluated in cellular models and on an enzyme, myeloperoxidase
(MPO), involved in inflammation. Microscopically leaf can be characterised by non
glandular and glandular trichomes, sinuous anticlinal epidermal cells, diacytic
stomata and helical vessels. Methanolic extract displayed high cellular
antioxidant activity at the concentrations range of 0.1-10 MUg mL-1 and 1-20 MUg
mL-1 using lucigenin on neutrophils and DCFH-DA on HL 60, respectively. This
extract also showed, more efficient effects on extracellular and intracellular
ROS production and MPO activity. Antioxidant and anti-inflammatory activities of
R. congoensis were significantly higher, positively correlated with their
phytochemical constituents such as flavonoids, iridoids and phenolic acids; and
could justify their use as traditional vegetable and potent local nutraceutical
resource.
PMID- 29338353
TI - Developing a Tailored Website for Promoting Awareness about Obstructive Sleep
Apnea (OSA) Among Blacks in Community-Based Settings.
AB - Blacks are at greater risk for lower sleep quality and higher risk for
obstructive sleep apnea (OSA) than other racial groups. In this study, we
summarize the development of a tailored website including visuals, key messages,
and video narratives, to promote awareness about sleep apnea among community
dwelling blacks. We utilized mixed methods, including in-depth interviews,
usability-testing procedures, and brief surveys (n = 9, 55% female, 100% black,
average age 38.5 years). Themes from the qualitative analysis illuminated varied
knowledge regarding OSA symptoms and prevalent self-reported experience with
sleep disturbance and OSA symptoms (e.g., snoring). On a scale from 1 (not at
all) to 5 (very high), participants provided favorable ratings of website
usefulness (mean = 4.9), user friendliness (mean = 4.9) and attractiveness (mean
= 4.3). Our findings suggest although tailored health communication has potential
for serving as a tool for advancing health equity, usability-testing of health
materials is critical to ensure that culturally and linguistically tailored
messages are acceptable and actionable in the intended population.
PMID- 29338354
TI - Teaching and Learning Across Two Cultures and Two Languages: German Health
Classification and Casemix Education Program.
PMID- 29338356
TI - Privacy Update: Community Attitudes towards Privacy.
PMID- 29338355
TI - New compounds with antimicrobial activities from Elaeodendron buchananii stem
bark.
AB - The plant species Elaeodendron buchananii Loes is widely used in folklore
medicine to manage microbial infections in Kenya. Previous studies on the plant
fruits and root bark revealed the presence of steroids and terpenoids. The
present phytochemical analysis of the plant stem bark has led to the isolation of
four new triterpenes characterized as methyl 3beta-acetoxy-11alpha, 19alpha, 28
trihydroxyurs-12-en-23-oic acid (1), 3beta, 11alpha, 19alpha-trihydroxyurs-12-en
23, 28-dioic acid (2), 3beta-acetoxy-19alpha, 23, 28-trihydroxyurs-12-ene (3) and
3-oxo-19alpha, 28-dihydroxyurs-12-en-24-oic acid (4), together with ten known
ones (5-14), whose structures were elucidated using spectroscopic techniques. The
isolate canophyllol (8) showed promising antibacterial activity against N.
meningitides with MIC value of 31.25 MUg/ml.
PMID- 29338357
TI - Clinical Terminologies, Health Classifications and the Health Information
Management Profession: Vital to All Sectors of the Healthcare System.
PMID- 29338358
TI - Chemical and Biological insights of Ouratea hexasperma (A. St.-Hil.) Baill.: a
source of bioactive compounds with multifunctional properties.
AB - The study aimed to evaluate in vitro antioxidant, anticholinesterase and
antidiabetic properties of Ouratea hexasperma (A. St.-Hil.) Baill. The
inflorescence methanol extract and the ethyl acetate fraction of leaves and stems
reported the highest Relative Antioxidant Capacity Index (RACI), whereas the
dichloromethane fraction of leaves was the best inhibitor of alpha-amylase and
alpha-glucosidase. Trans-3-O-methyl-resveratrol-2-C-beta-glucoside,
lithospermoside, 2,5-dimethoxy-p-benzoquinone, lup-20(30)-ene-3beta,28-diol, 7-O
methylgenistein, apigenin and luteolin and amentoflavone were isolated from O.
hexasperma. Resveratrol derivative was isolated for the first time in Ochnaceae
family. Luteolin, followed by apigenin, reported the highest Relative Antioxidant
Capacity Index and they were also the best inhibitors of alpha-glucosidase
enzyme.
PMID- 29338359
TI - Characterization of moso bamboo (Phyllostachys edulis) Dof transcription factors
in floral development and abiotic stress responses.
AB - The Dof transcription factor (TF) family belongs to a class of plant-specific TFs
and is involved in plant growth, development, and response to abiotic stresses.
However, there are only very limited reports on the characterization of Dof TFs
in moso bamboo (Phyllostachys edulis). In the present research, PheDof TFs showed
specific expression profiles based on RNA-seq data analyses. The co-expression
network indicated that PheDof12, PheDof14, and PheDof16 might play vital roles
during flower development. Cis-regulatory element analysis of these PheDof genes
suggested diverse functions. Expression patterns of 12 selected genes from seven
different classes under three abiotic stresses (cold, salt, and drought) are
further investigated by quantitative real-time PCR. This work will provide useful
information for functional analysis and regulation mechanisms of Dof TFs in moso
bamboo.
PMID- 29338361
TI - Pursue the Challenge: A New Graduate's Experience.
PMID- 29338360
TI - The Implementation of New Morbidity Classifications in Canada.
AB - Canada is in the midst of a staggered implementation of the International
Statistical Classification of Diseases and Related Health Problems, Tenth
Revision, Canada (ICD-10-CA) and the Canadian Classification of Health
Interventions (CCI). These classifications are more comprehensive than historical
standards and their capacity extends beyond the scope of their predecessor
classifications. Canada is the first country to produce the new classifications
in a database, with the final product in an infobase format. The Canadian
Institute for Health Information (CIHI) was responsible for the enhancement of
ICD-10-CA, the development of CCI, the education of coders, and the provision of
post-implementation support.
PMID- 29338362
TI - Coder Educator: The Way Forward.
AB - The introduction of a new Coder Educator position in the Coding Unit at the
Princess Alexandra Hospital, Brisbane, Queensland, has been a key strategy in the
development and maintenance of a skilled coding workforce, the improvement of the
level of knowledge of the coding staff, and the provision of a career structure
for clinical coders. In this report, the experience is related from the
perspectives of the Coding Manager and the Coder Educator.
PMID- 29338363
TI - The Impact of the Technical/Technological Background of Medical and Paramedical
Staff on the Efficiency of a Digital Medical Information System Introduced at a
State Hospital Department.
PMID- 29338364
TI - Implementation of Privacy Legislation and Principles: A Private Hospital
Perspective.
PMID- 29338365
TI - Developing and Managing the National Coroners' Information System for Australia.
PMID- 29338366
TI - Risk Management - What's in it for Health Information Managers?
PMID- 29338367
TI - Making a Quality Start: A Coder Orientation Program.
AB - Orienting new clinical coders to the hospital's case mix should be a basic
function of the organisation's Coding Service. After much trial and error,
Southern Health Coding and Casemix Services has devised an orientation program
that brings together, in a structured and logical manner, all the elements a
coder needs to know. This article describes the current coding orientation
program.
PMID- 29338368
TI - An Australian Standard for Health Care Client Identification.
PMID- 29338370
TI - The Statewide Client Registration Project Initiated by the Tasmanian Department
of Health & Human Services.
PMID- 29338369
TI - Snomed(r) CT: The Fit with Classification in Health.
AB - Classification systems are the primary means for automated retrieval and analysis
of healthcare data from individual patient medical records. This article will
provide a brief history and overview of the two most comprehensive and advanced
controlled clinical terminologies in the world: the Systematized Nomenclature of
Medicine Reference Terminology (SNOMED(r) RT), and Clinical Terms Version 3
(CTV3). A discussion will follow of the merger of these two terminologies into a
single new work, SNOMED(r) Clinical Terms (SNOMED(r) CT), as released in early
2002, how it is used to retrieve data, how it differs from a classification, and
the opportunities open to health information management professionals to expand
their roles as information managers through their knowledge of SNOMED CT.
PMID- 29338371
TI - Health Information Services in the West Pilbara Health Service, North-Western
Australia.
PMID- 29338372
TI - Getting it Right: Meeting the Aged Care Accreditation Standards.
AB - The aged care industry in Australia has been faced with many challenges over the
last five years, including the introduction of the Aged Care Act 1997 and the
Aged Care Accreditation Standards. The purpose of the introduction of the
accreditation process was to ensure that residential aged care services were
complying with the Accreditation Standards and making a commitment to
continuously improve their standard of care and services (Aged Care Standards and
Accreditation Agency, 2000). This article describes how one service has
implemented a management system approach to ensure compliance with the Aged Care
Accreditation Standards.
PMID- 29338373
TI - Nursing Classification and Terminology Systems.
AB - A number of terminologies exist that represent concepts of relevance to nurses,
although none of these is in use by Australian nurses. Without consensus, nursing
language and definitions incorporated in clinical information systems now being
implemented will continue to vary considerably. The result will be an inability
to compare nursing practice, or to aggregate data for research purposes, or to
collect national statistical data to demonstrate the significance of nurses'
contributions to health care. This article provides an international historical
overview of nursing terminology developments relative to what is happening in
Australia, brief reviews of the many available nursing terminologies, an update
of this work relative to activities being undertaken towards the development and
adoption of standards, and a discussion about desirable future research and
development activities.
PMID- 29338374
TI - Accreditation in Primary Health: RACGP Standards for General Practice.
AB - General Practitioners play a crucial role as "gate-keepers" to the health system.
In this context, they have a profound influence on both health outcomes and
health expenditure. Since the introduction in 1999 of a formal, peer-driven
external accreditation process, over 4,590 Australian general practices have
achieved full accreditation. The process of re-ccreditation has commenced,
subsequent to a review of the original standards, and with an ongoing focus on
continuous quality improvement. This article describes a typical accreditation
survey visit, and explains the accreditation criteria and how they are reviewed
by the surveyors. There is discussion also of the impact of this new
accreditation system on general practice.
PMID- 29338375
TI - Information and Case Mix Funding.
PMID- 29338376
TI - Australian Classification of Health Interventions - Adapted for International Use
(ACHI-I).
PMID- 29338377
TI - The Research and Public Consultation Process Undertaken in the Development of AR
DRG Version 5.0.
PMID- 29338378
TI - Health Information Management in the Australian Health Care System as a Whole.
PMID- 29338379
TI - Factors Affecting Survival in Children With Pericardial Effusion After
Hematopoietic Stem Cell Transplantation.
AB - The objective of this study was to determine the incidence, risk factors,
outcome, and clinical significance of pericardial effusion (PE). We
retrospectively analyzed outcomes of 272 pediatric patients undergoing their
first hematopoietic stem cell transplantation (HSCT) from 1998 to 2016. In total,
15% (3/20) and 5.9% (15/252) of autologous and allogeneic HSCT recipients,
respectively, were identified with PE. However, there was no statistically
significant difference in the incidence of PE between the 2 groups. The mean age
at transplantation was 11.12 +/- 5.41 y. Eighteen patients developed PE at 4.13
+/- 4.44 mo after HSCT. PE was confirmed by echocardiogram in all patients. Three
patients presented with severe PE with cardiac tamponade and required urgent
pericardiocentesis. Overall survival (OS) rates for patients who developed PE
were 83.3% and 38.9% at 100 d and 3 y, respectively, after HSCT. Death was not
directly attributable to PE in patients who died in the first year after HSCT.
Multivariable analysis identified the following variables to be associated with
OS: PE (relative risk[RR]: 3.70; 95% confidence interval [95% CI]: 1.89-7.23; P <
0.001), active disease at HSCT (RR: 1.59; 95% CI: 1.02-2.49; P < 0.001), and
thalassemia (RR: 0.62; 95% CI: 0.45-0.84; P < 0.001). PE is, thus, a debilitating
and significant complication of pediatric HSCT. Therefore, prospective studies
are required for better determination of the etiology and optimal method of PE
treatment after HSCT.
PMID- 29338380
TI - Transplantation of Human Neural Progenitor Cells Reveals Structural and
Functional Improvements in the Spastic Han-Wistar Rat Model of Ataxia.
AB - The use of regenerative medicine to treat nervous system disorders like ataxia
has been proposed to either replace or support degenerating neurons. In this
study, we assessed the ability of human neural progenitor cells (hNPCs) to repair
and restore the function of dying neurons within the spastic Han-Wistar rat
(sHW), a model of ataxia. The sHW rat suffers from neurodegeneration of specific
neurons, including cerebellar Purkinje cells and hippocampal CA3 pyramidal cells
leading to the observed symptoms of forelimb tremor, hind-leg rigidity, gait
abnormality, motor incoordination, and a shortened life span. To alleviate the
symptoms of neurodegeneration and to replace or augment dying neurons, neuronal
human progenitor cells were implanted into the sHW rats. At 30 d of age, male sHW
mutant rats underwent subcutaneous implantation of an Alzet osmotic pump that
infused cyclosporine (15 mg/kg/d) used to suppress the rat's immune system. At 40
d, sHW rats received bilateral injections (500,000 cells in 5 uL media) of live
hNPCs, dead hNPCs, live human embryonic kidney cells, or growth media either into
the cerebellar cortex or into the hippocampus. To monitor results, motor activity
scores (open-field testing) and weights of the animals were recorded weekly. The
sHW rats that received hNPC transplantation into the cerebellum, at 60 d of age,
displayed significantly higher motor activity scores and sustained greater
weights and longevities than control-treated sHW rats or any hippocampal
treatment group. In addition, cerebellar histology revealed that the transplanted
hNPCs displayed signs of migration and signs of neuronal development in the
degenerated Purkinje cell layer. This study revealed that implanted human
progenitor cells reduced the ataxic symptoms in the sHW rat, identifying a future
clinical use of these progenitor cells against ataxia and associated
neurodegenerative diseases.
PMID- 29338381
TI - Effect of the Diabetic State on Islet Engraftment and Function in a Large Animal
Model of Islet-Kidney Transplantation.
AB - In islet transplantation, in addition to immunologic and ischemic factors, the
diabetic/hyperglycemic state of the recipient has been proposed, although not yet
validated, as a possible cause of islet toxicity, contributing to islet loss
during the engraftment period. Using a miniature swine model of islet
transplantation, we have now assessed the effect of a persistent state of
hyperglycemia on islet engraftment and subsequent function. An islet-kidney (IK)
model previously described by our laboratory was utilized. Three experimental
donor animals underwent total pancreatectomy and autologous islet transplantation
underneath the renal capsule to prepare an IK at a load of <=1,000 islet
equivalents (IE)/kg donor weight, leading to a chronic diabetic state during the
engraftment period (fasting blood glucose >250 mg/dL). Three control donor
animals underwent partial pancreatectomy (sufficient to maintain normoglycemia
during islet engraftment period) and IK preparation. As in vivo functional
readout for islet engraftment, the IKs were transplanted across an immunologic
minor or class I mismatch barrier into diabetic, nephrectomized recipients at an
islet load of ~4,500 IE/kg recipient weight. A 12-d course of cyclosporine was
administered for tolerance induction. All experimental donors became diabetic and
showed signs of end organ injury, while control donors maintained normoglycemia.
All recipients of IK from both experimental and control donors achieved glycemic
control over long-term follow-up, with reversal of diabetic nephropathy and with
similar glucose tolerance tests. In this preclinical, large animal model, neither
islet engraftment nor subsequent long-term islet function after transplantation
appear to be affected by the diabetic state.
PMID- 29338382
TI - Mounting of Biomaterials for Use in Ophthalmic Cell Therapies.
AB - When used as scaffolds for cell therapies, biomaterials often present basic
handling and logistical problems for scientists and surgeons alike. The quest for
an appropriate mounting device for biomaterials is therefore a significant and
common problem. In this review, we provide a detailed overview of the factors to
consider when choosing an appropriate mounting device including those experienced
during cell culture, quality assurance, and surgery. By way of example, we draw
upon our combined experience in developing epithelial cell therapies for the
treatment of eye diseases. We discuss commercially available options for
achieving required goals and provide a detailed analysis of 4 experimental
designs developed within our respective laboratories in Australia, the United
Kingdom, and Belgium.
PMID- 29338383
TI - The Process of Engraftment of Myogenic Cells in Skeletal Muscles of Primates:
Understanding Clinical Observations and Setting Directions in Cell
Transplantation Research.
AB - We studied in macaques the evolution of the intramuscular transplantation of
muscle precursor cells between the time of administration and the time at which
the graft is considered stable. Satellite cell-derived myoblasts labeled with
beta-galactosidase were transplanted into 1 cm3 muscle regions following cell
culture and transplantation protocols similar to our last clinical trials. These
regions were biopsied 1 h, 1, 3, 7 d, and 3 wk later and analyzed by histology.
We observed that the cell suspension leaks from the muscle bundles during
injection toward the epimysium and perimysium, where most cells accumulate after
transplantation. We observed evidence of necrosis, apoptosis, and mitosis in the
accumulations of grafted cells, and of potential migration to participate in
myofiber regeneration in the surrounding muscle bundles. After 3 wk, the compact
accumulations of grafted cells left only some graft-derived myotubes and small
myofibers in the perimysium. Hybrid myofibers were abundant in the muscle
fascicles at 3 wk posttransplantation, and they most likely occur by grafted
myoblasts that migrated from the peripheral accumulations than by the few
remaining within the fascicles immediately after injection. These observations
explain the findings in clinical trials of myoblast transplantation and provide
information for the future research in cell therapy in myology.
PMID- 29338384
TI - Human Umbilical Cord Mesenchymal Stem Cells Preserve Adult Newborn Neurons and
Reduce Neurological Injury after Cerebral Ischemia by Reducing the Number of
Hypertrophic Microglia/Macrophages.
AB - Microglia are the first source of a neuroinflammatory cascade, which seems to be
involved in every phase of stroke-related neuronal damage. Two weeks after
transient middle cerebral artery occlusion (MCAO), vehicle-treated rats displayed
higher numbers of total ionized calcium-binding adaptor molecule 1 (Iba-1)
positive cells, greater cell body areas of Iba-1-positive cells, and higher
numbers of hypertrophic Iba-1-positive cells (with a cell body area over 80 MUm2)
in the ipsilateral ischemic brain regions including the frontal cortex, striatum,
and parietal cortex. In addition, MCAO decreased the number of migrating
neuroblasts (or DCX- and 5-ethynyl-2'-deoxyuridine-positive cells) in the cortex,
subventricular zone, and hippocampus of the ischemic brain, followed by
neurological injury (including brain infarct and neurological deficits).
Intravenous administration of human umbilical cord-derived mesenchymal stem cells
(hUC-MSCs; 1 * 106 or 4 * 106) at 24 h after MCAO reduced neurological injury,
decreased the number of hypertrophic microglia/macrophages, and increased the
number of newborn neurons in rat brains. Thus, the accumulation of hypertrophic
microglia/macrophages seems to be detrimental to neurogenesis after stroke.
Treatment with hUC-MSCs preserved adult newborn neurons and reduced functional
impairment after transient cerebral ischemia by reducing the number of
hypertrophic microglia/macrophages.
PMID- 29338385
TI - Does the Mesenchymal Stem Cell Source Influence Smooth Muscle Regeneration in
Tissue-Engineered Urinary Bladders?
AB - A variety of tissue engineering techniques utilizing different cells and
biomaterials are currently being explored to construct urinary bladder walls de
novo, but so far no approach is clearly superior. The aim of this study was to
determine whether mesenchymal stem cells (MSCs) isolated from different sources,
(bone marrow [BM-MSCs] and adipose tissue [ADSCs]), differ in their potential to
regenerate smooth muscles in tissue-engineered urinary bladders and to determine
an optimal number of MSCs for urinary bladder smooth muscle regeneration. Forty
eight rats underwent hemicystectomy and bladder augmentation with approximately
0.8 cm2 graft. In the first and second groups, urinary bladders were
reconstructed with small intestinal submucosa (SIS) seeded with 10 * 106 or 4 *
106 ADSCs/cm2, respectively. In the third and fourth groups, urinary bladders
were augmented with SIS seeded with 10 * 106 or 4 * 106 BM-MSCs/cm2,
respectively. In the fifth group, urinary bladders were augmented with SIS
without cells. The sixth group (control) was left intact. Smooth muscle
regeneration was evaluated by real-time polymerase chain reaction (RT-PCR) and
histological examinations. Histologically, there were no significant differences
between urinary bladders augmented with ADSCs and BM-MSCs, but there was a marked
increase in smooth muscle formation in bladders augmented with grafts seeded with
MSCs in higher density (10 * 106/cm2) compared to lower density (4 * 106/cm2).
Molecular analysis revealed that bladders reconstructed with ADSC-seeded grafts
expressed higher levels of smooth muscle myosin heavy chain, caldesmon, and
vinculin. Bladders augmented with unseeded SIS were fibrotic and devoid of smooth
muscles. ADSCs and BM-MSCs have comparable smooth muscle regenerative potential,
but the number of MSCs used for graft preparation significantly affects the
smooth muscle content in tissue-engineered urinary bladders.
PMID- 29338387
TI - Quantifying the Effects of Different Neutral Proteases on Human Islet Integrity.
AB - Efficient islet release from the pancreas requires the combination of
collagenase, neutral protease (cNP), or thermolysin (TL). Recently, it has been
shown that clostripain (CP) may also contribute to efficient islet release from
the human pancreas. The aim of this study was to evaluate the impact of these
proteases on human islet integrity in a prospective approach. Islets were
isolated from the pancreas of 10 brain-dead human organ donors. Purified islets
were precultured for 3 to 4 d at 37 degrees C to ensure that preparations were
cleared of predamaged islets, and only integral islets were subjected to 90 min
of incubation at 37 degrees C in Hank's balanced salt solution supplemented with
cNP, TL, or CP. The protease concentrations were calculated for a pancreas of 100
g trimmed weight utilizing 120 dimethyl-casein units of cNP, 70,000 caseinase
units of TL, or 200 benzoyl-l-arginine-ethyl-ester units of CP (1*). These
activities were then increased both 5* and 10*. After subsequent 24-h culture in
enzyme-free culture medium, treated islets were assessed and normalized to sham
treated controls. Compared with controls and CP, islet yield was significantly
reduced by using the 5* activity of cNP and TL, inducing also fragmentation and
DNA release. Viability significantly decreased not until adding the 1* activity
of cNP, 5* activity of TL, or 10* activity of CP. Although mitochondrial function
was significantly lowered by 1* cNP and 5* TL, CP did not affect mitochondria at
any concentration. cNP- and TL-incubated islets significantly lost intracellular
insulin already at 1* activity, while the 10* activity of CP had to be added to
observe a similar effect. cNP and TL have a similar toxic potency regarding islet
integrity. CP also induces adverse effects on islets, but the toxic threshold is
generally higher. We hypothesize that CP can serve as supplementary protease to
minimize cNP or TL activity for efficient pancreas digestion.
PMID- 29338386
TI - Estrogen-Estrogen Receptor alpha Signaling Facilitates Bilirubin Metabolism in
Regenerating Liver Through Regulating Cytochrome P450 2A6 Expression.
AB - BACKGROUND: After living donor liver transplantation (LDLT), rising serum
bilirubin levels commonly indicate insufficient numbers of hepatocytes are
available to metabolize bilirubin into biliverdin. Recovery of bilirubin levels
is an important marker of hepatocyte repopulation after LDLT. Cytochrome P450
(CYP) 2A6 in humans (or cyp2a4 in rodents) can function as "bilirubin oxidase."
Functional hepatocytes contain abundant CYP2A6, which is considered a marker for
hepatocyte function recovery. The aim of our study was to determine the impact of
estradiol/estrogen receptor signaling on bilirubin levels during liver function
recovery. METHODS: We conducted a hospital-based cohort study of bilirubin levels
after LDLT surgery in both liver graft donors and recipients, performed a
transcriptome comparison of wild-type versus estrogen receptor (ER)alpha knockout
mice and a bioinformatics analysis of transcriptome changes in their regenerating
liver after two-third partial hepatectomy (PHx), and assayed in vitro expression
of cytochrome (CYP2A6) in human hepatic progenitor cells (HepRG) treated with
17beta-estradiol (E2). RESULTS: The latency of bilirubin level reduction was
shorter in women than in men, suggesting that a female factor promotes bilirubin
recovery after liver transplantation surgery. In the PHx mouse model, the
expression of the cyp2a4 gene was significantly lower in livers from the knockout
ERalpha mice than in livers from their wild-type littermates; but the expression
of other bilirubin metabolism-related genes were similar between these groups.
Moreover, E2 or bilirubin treatments significantly promoted CYP2A6 expression in
hepatocyte progenitor cells (HepRG cells). Sequence analysis revealed similar
levels of aryl hydrocarbon receptor (AhR; bilirubin responsive nuclear receptor)
and ESR1 binding to the promoter region of CYP2A6. CONCLUSIONS: This is the first
report to demonstrate, on a molecular level, that E2/ERalpha signaling
facilitates bilirubin metabolism in regenerating liver. Our findings contribute
new knowledge to our understanding of why the latency of improved bilirubin
metabolism and thereby liver function recovery is shorter in females than in
males.
PMID- 29338389
TI - Privacy Officer: A Role for Health Information Managers.
AB - Health information managers (HIMs) are experts in the protection and management
of health information within patient records and information systems. New privacy
legislation in Australia has raised the importance of this protection and a new
role of Privacy Officer is evolving. HIMs are well positioned to take on this
role and its associated responsibilities. Here, a Privacy Officer from Victoria
provides an insight into the position and its opportunities.
PMID- 29338391
TI - Development of a National Standard for the Identification of Health Care
Providers.
PMID- 29338390
TI - Preparing for New Health Privacy Legislation in Rural Australia.
AB - This Rural Professional Practice item describes the benefits of a collaborative,
regional approach to implementing new health privacy legislation.
Videoconferencing has been adopted to surmount the problems of long-distance
communication between the Privacy Officers of 11 regional health services spread
throughout a large region of south-eastern Australia.
PMID- 29338388
TI - Novel Fusion Protein Targeting Mitochondrial DNA Improves Pancreatic Islet
Functional Potency and Islet Transplantation Outcomes.
AB - Long-term graft survival is an ongoing challenge in the field of islet
transplantation. With the growing demand for transplantable organs, therapies to
improve organ quality and reduce the incidence of graft dysfunction are of
paramount importance. We evaluated the protective role of a recombinant DNA
repair protein targeted to mitochondria (Exscien I-III), as a therapeutic agent
using a rodent model of pancreatic islet transplantation. We first investigated
the effect of therapy on isolated rat islets cultured with pro-inflammatory
cytokines (interleukin-1 beta, interferon gamma, and tumor necrosis factor alpha)
for 48 h and documented a significant reduction in apoptosis by flow cytometry,
improved viability by immunofluorescence, and conserved functional potency in
vitro and in vivo in Exscien I-III-treated islets. We then tested the effect of
therapy in systemic inflammation using a rat model of donor brain death (BD)
sustained for a 6-h period. Donor rats were allocated to 4 groups: (non-BD +
vehicle, non-BD + Exscien I-III, BD + vehicle, and BD + Exscien I-III) and
treated with Exscien I-III (4 mg/kg) or vehicle 30 min after BD induction. Sham
(non-BD)-operated animals receiving either Exscien I-III or vehicle served as
controls. Islets purified from BD + Exscien I-III-treated donors showed a
significant increase in glucose-stimulated insulin release in vitro when compared
to islets from vehicle-treated counterparts. In addition, donor treatment with
Exscien I-III attenuated the effects of BD and significantly improved the
functional potency of transplanted islets in vivo. Our data indicate that
mitochondrially targeted antioxidant therapy is a novel strategy to protect
pancreas and islet quality from the deleterious effects of cytokines in culture
and during the inflammatory response associated with donation after BD. The
potential for rapid translation into clinical practice makes Exscien I-III an
attractive therapeutic option for the management of brain-dead donors or as an
additive to islets in culture after isolation setting.
PMID- 29338392
TI - What is Quality in Health Care?
PMID- 29338393
TI - Overview of the New South Wales Health Unique Patient Identifier Project.
PMID- 29338394
TI - Reference Terminologies.
PMID- 29338395
TI - The University of Sydney, Sydney, New South Wales.
PMID- 29338396
TI - Queensland University of Technology, Brisbane, Queensland.
PMID- 29338397
TI - Regarding Questions and Principles.
PMID- 29338398
TI - Valuing Your Past to Provide a Stronger Future - A Queensland Perspective on
Professional Development at the State Level.
PMID- 29338399
TI - The 2nd National Health Online Summit, Brisbane 3-4 March 2003.
AB - The first conference was held in Adelaide in August 2000. The conference was an
initiative of the National Health Information Management Advisory Council
(NHIMAC). NHIMAC was established in 1998 by the Australian Health Ministers to
advise on options to promote a nationally uniform approach to more effective
information management in the health sector. The second conference was held in
Brisbane in March 2003, and this paper provides an overview of the key issues
addressed there.
PMID- 29338401
TI - From Shanghai to Guangzhou: Interest in Health Information Management from China.
PMID- 29338400
TI - Excerpts from the IFHRO Handbook on Health Record Education.
PMID- 29338402
TI - Research in Health Information Management Practice.
PMID- 29338403
TI - Guardians of Knowledge: The Paradigm of Confidentiality.
PMID- 29338404
TI - Understanding Neurobiological Implications of Maltreatment: A focus on children
and youth.
PMID- 29338405
TI - Graduate Student/Postdoctoral Fellow Section of Child Maltreatment Editorial
Board.
PMID- 29338406
TI - A Decade of the Australian Casemix Classification.
PMID- 29338407
TI - La Trobe University, Melbourne, Victoria.
PMID- 29338408
TI - 10th European Conference on Health Records, Dublin, Ireland, 25-29 August 2002:
Managing Health Information in the 21st Century.
PMID- 29338409
TI - Announcing: The 14th Congress of the International Federation of Health Records
Organizations, in Conjunction with the American Health Information Management
Association 76th National Convention and Exhibit - Washington, DC, USA, 9-14
October, 2004.
PMID- 29338410
TI - Uses of Health Information.
PMID- 29338411
TI - Update from the IFHRO Executive Committee.
PMID- 29338412
TI - International Reflections.
PMID- 29338413
TI - HIMAA and Education.
PMID- 29338414
TI - HIM Education Advances.
PMID- 29338415
TI - AHIMA Project Offers Insights into SNOMED, ICD-9-CM Mapping Process.
PMID- 29338416
TI - Data Quality Management at Hong Kong Public Hospitals.
PMID- 29338417
TI - Editorial.
PMID- 29338418
TI - Once upon a Time ... the Power of Story and Learning Journals.
AB - This paper will invite you to consider the role of stories for learning and the
use of learning journals as a tool to create meaning. The application of story
and story culture in higher education, academia and management contexts will be
presented. As an example, an old Punjabi tale will be adapted for use when
managing and inspiring teams in the workplace. Storytelling is experiencing a
revival and being used in the corporate sector to ignite action in knowledge-era
organisations.
PMID- 29338419
TI - A Review of Health Information Management Education in China.
PMID- 29338421
TI - A Decade of Casemix Funding in Victoria.
PMID- 29338420
TI - Curtin University of Technology, Perth, Western Australia.
PMID- 29338422
TI - Professional Development - South Australian Branch of HIMAA Update.
PMID- 29338424
TI - International Federation of Health Records Organizations (IFHRO) - Newsletter.
PMID- 29338423
TI - Production of thermostable multiple enzymes from Bacillus amyloliquefaciens
KUB29.
AB - A strain of Bacillus amyloliquefaciens KUB29 was identified by 16S ribosomal RNA
sequencing (Genbank: MF772779.1). Production of thermostable protease, amylase
and lipase were done by the isolated strain. The produced enzymes were partially
purified by ammonium precipitation followed by dialysis process. Protease and
lipase enzymes are effectively used in bio-oil extraction from proteinaceous
sample followed by transesterification to produce methyl ester. Amylase enzyme is
widely used in food and laundry industry. The produced enzymes are active at
thermophilic condition of 55 degrees C. Use of these enzymes in biofuel
production process will make the process cleaner and greener.
PMID- 29338425
TI - Correction: Re: Acknowledgment: A Profile of Coding Staff in Sydney Metropolitan
Public Hospitals Health Information Management, Vol 32(2).
AB - The authors would like to thank Adam Bennett, who collected the raw data used in
this study for his thesis submitted for the degree of Bachelor of Applied Science
(Health Information Management) (Honours) at The University of Sydney.
PMID- 29338426
TI - Evolution, Not Revolution: Measurement and Management of Health Outcomes in New
Zealand through Efficient Use of National Information Systems.
AB - The development of health information systems is not always successful, and there
is an emerging perception that money and time that could be better directed to
patient care are being wasted on these systems. This paper examines the
difficulties faced in creating successful information systems in health services,
and suggests strategies for overcoming these difficulties. The development of
information systems is a precursor to the use of data in the management of
processes which lead towards improved health outcomes. It is argued that before
embarking upon difficult and costly new developments, researchers should treat
existing sources of data as their first point of call, and New Zealand's existing
national data sources are described in detail. Ways in which these data are being
used to develop outcome measures are discussed, and it is concluded that through
a multidisciplinary approach existing resources could be utilised more
efficiently and effectively to achieve this goal.
PMID- 29338427
TI - Lipid nanoparticles for intranasal administration: application to nose-to-brain
delivery.
AB - INTRODUCTION: The blood brain barrier is a functional barrier allowing the entry
into the brain of only essential nutrients, excluding other molecules. Its
structure, although essential to keep the harmful entities out, is also a major
roadblock for pharmacological treatment of brain diseases. Several alternative
invasive drug delivery approaches, such as transcranial drug delivery and
disruption of blood brain barrier have been explored, with limited success and
several challenges. Intranasal delivery is a non-invasive methodology, which
bypasses the systemic circulation, and, through the intra- and extra- neuronal
pathways, provides direct brain drug delivery. Colloidal drug delivery systems,
particularly lipidic nanoparticles offer several unique advantages for this goal
. Areas covered: This review focuses on key brain diseases such as Alzheimer's
disease, Parkinson's disease, Huntington's disease and amyotrophic lateral
sclerosis, and provide a detailed overview of the current lipid nanoparticle
based treatment options explored thus far. The review also delves into basic
preparation, challenges and evaluation methods of lipid drug delivery systems.
Expert opinion: Brain diseases present complex pathophysiology, in addition to
the practically inaccessible brain tissues, hence according to the authors, a two
pronged approach utilizing new target discovery coupled with new drug delivery
systems such as lipid carriers must be adopted.
PMID- 29338428
TI - HIMAA President Receives Award.
PMID- 29338429
TI - Study of aflatoxicosis reduction: effect of Alchornea cordifolia on biomarkers in
an aflatoxin B1 exposed rats.
AB - The toxicity of aflatoxins results in cancer and liver disease. Several natural
substances such as plants exhibited their ability to inhibit the initiation of
aflatoxin carcinogenesis. The aim of this study was to evaluate the effect of
Alchornea cordifolia on biomarkers in an aflatoxin B1 (AFB1) exposed rats. The
contents of polyphenols, flavonoids and the antioxidant activity of A. cordifolia
ethanolic leaf extract (EELac) were assessed. Groups of rats were treated orally
with a daily dose of a mixture of AFB1 at a dose of 150 MUg/kg body weight and
EELac (50, 100 and 300 mg/kg body weight) for 21 days. Biomarkers of AFB1, such
as the AFB1-lysine adduct and aflatoxin M1 were assayed in blood and urine,
respectively, using an HPLC system with a fluorescence detector. The contents of
polyphenols and flavonoids were 6783.23 +/- 272.76 MUg EAG/g and 10.54 +/- 3.15%
of dry matter, respectively. EELac showed a good antioxidant activity (IC50 =
12.65 +/- 0.13 MUg/mL). The administration of the mixture (AFB1 + EELac) at
different doses significantly reduced the level of AFB1-lysine adduct from 14.04
+/- 2.1 to 4.13 +/- 0.9 ng/mg albumin and that of Aflatoxin M1 (AFM1) from 456 +/
16 to 220 +/- 24 ng/mL (p <0.05). The rate of reduction was 70.58% for AFB1
lysine adduct and 51.75% for AFM1. A. cordifolia could be used in the prevention
of toxicity induced by AFB1 on account of its high content in phenolic compounds.
PMID- 29338430
TI - State-Level Point-of-Sale Tobacco News Coverage and Policy Progression Over a 2
Year Period.
AB - BACKGROUND: Mass media content may play an important role in policy change.
However, the empirical relationship between media advocacy efforts and tobacco
control policy success has rarely been studied. We examined the extent to which
newspaper content characteristics (volume, slant, frame, source, use of evidence,
and degree of localization) that have been identified as important in past
descriptive studies were associated with policy progression over a 2-year period
in the context of point-of-sale (POS) tobacco control. METHOD: We used regression
analyses to test the relationships between newspaper content and policy
progression from 2012 to 2014. The dependent variable was the level of
implementation of state-level POS tobacco control policies at Time 2. Independent
variables were newspaper article characteristics (volume, slant, frame, source,
use of evidence, and degree of localization) and were collected via content
analysis of the articles. State-level policy environment contextual variables
were examined as confounders. RESULTS: Positive, significant bivariate
relationships exist between characteristics of news content (e.g., high overall
volume, public health source present, local quote and local angle present, and
pro-tobacco control slant present) and Time 2 POS score. However, in a
multivariate model controlling for other factors, significant relationships did
not hold. DISCUSSION: Newspaper coverage can be a marker of POS policy
progression. Whether media can influence policy implementation remains an
important question. Future work should continue to tease out and confirm the
unique characteristics of media content that are most associated with subsequent
policy progression, in order to inform media advocacy efforts.
PMID- 29338432
TI - Working in Vanuatu.
PMID- 29338431
TI - Medically induced hypertension, hypervolaemia and haemodilution for the treatment
and prophylaxis of vasospasm following aneurysmal subarachnoid haemorrhage:
systematic review.
AB - PURPOSE: Arterial vasospasm is a major cause of death and long-term disability
following subarachnoid haemorrhage (SAH). The use of medically induced
hypertension, hypervolaemia and/or haemodilution is widely practiced for
prophylaxis and treatment of vasospasm following SAH. We aimed to determine if
the quality of available research is adequate to inform use of haemodynamic
management strategies to prevent or treat vasospasm following SAH. METHODS:
Individual searches of the following databases were conducted: The Cochrane
Database of Systematic Reviews, The Cochrane Central Register of Controlled
Trials, MEDLINE, EMBASE and OpenSIGLE. Pertinent randomised clinical trials and
cohort studies comparing any element or combination thereof: medically induced
hypertension, hypervolaemia, and haemodilution were included. Data were extracted
using standardised proformas and risk of bias assessed using a domain-based risk
of bias assessment tool. RESULTS: 348 study reports were identified by our
literature search. Eight studies were included, three of which examined both
volume expansion and medically induced hypertension. Three randomised clinical
trials and two cohort studies examining prophylactic volume expansion were
included. Two trials of prophylactic medically induced hypertension and two
cohort studies were included. One trial and one cohort study of medically induced
hypertension for treatment of established vasospasm was included. These trials
demonstrated no significant difference in any of the clinical outcome measures
studied. No trials of blood transfusion were included. CONCLUSIONS: There is
currently insufficient evidence to determine the efficacy or non-efficacy of
intravenous volume expansion, medically induced hypertension or blood transfusion
for the treatment or prophylaxis of vasospasm following SAH. All of these
approaches have been associated with adverse events, of unclear incidence. The
current evidence base therefore cannot be used to reliably inform clinical
practice. This is a priority for further research.
PMID- 29338433
TI - In Vivo Ovarian Cancer Gene Therapy Using CRISPR-Cas9.
AB - Clustered regularly interspaced short palindromic repeats (CRISPR)-caspase 9
(Cas9) genome editing technology holds great promise for the field of human gene
therapy. However, a lack of safe and effective delivery systems restricts its
biomedical application. Here, a folate receptor-targeted liposome (F-LP) was used
to deliver CRISPR plasmid DNA co-expressing Cas9 and single-guide RNA targeting
the ovarian cancer-related DNA methyltransferase 1 (DNMT1) gene (gDNMT1). F-LP
efficiently bound the gDNMT1 plasmid and formed a stable complex (F-LP/gDNMT1)
that was safe for injection. F-LP/gDNMT1 effectively mutated endogenous DNMT1 in
vitro, and then expressed the Cas9 endonuclease and downregulated DNMT1 in vivo.
The tumor growth of both paclitaxel-sensitive and -resistant ovarian cancers were
inhibited by F-LP/gDNMT1, which shows fewer adverse effects than paclitaxel
injection. Therefore, CRISPR-Cas9-targeted DNMT1 manipulation may be a potential
therapeutic regimen for ovarian cancer, and lipid-mediated delivery systems
represent promising delivery vectors of CRISPR-Cas9 technology for precise genome
editing therapeutics.
PMID- 29338434
TI - Standardising Client Identification across Adelaide Public Hospitals - An Update.
AB - To be able to integrate health information across multiple systems and locations,
it is essential that the collection and maintenance of key client identifying
demographic data be standardised. South Australia is now moving towards a
rigorous approach of client identification across the eight public metropolitan
hospitals to support the rollout of a clinical information system. The system is
being implemented for all clinical services and an estimated 8,000 doctors,
nurses and allied health professionals have been trained in its use. This paper
discusses the development and scope of a new set of client identification data
standards (for hospitals only) that have been designed to support this project.
PMID- 29338436
TI - The Value of Continuing Professional Development.
PMID- 29338435
TI - Three new diphenyl ether derivatives from the fermentation products of an
endophytic fungus Phomopsis fukushii.
AB - Three new diphenyl ethers (1-3), together with four known isopentylated diphenyl
ethers derivatives (4-7), were isolated from the fermentation products of an
endophytic fungus Phomopsis fukushii. Their structures were elucidated by
spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1
3 were evaluated for their anti-methicillin-resistant Staphylococcus aureus (anti
MRSA) activity. The results revealed that compounds 1 and 2 showed strong
inhibitions with inhibition zone diameters (IZD) of 20.2 +/- 2.5 mm and 17.9 +/-
2.2 mm, respectively. Compound 3 also showed good inhibition with IZD 15.2 +/-
1.8 mm. The IZD data of compound 1 is close to that of positive control with IZD
21.9 +/- 2.1 mm.
PMID- 29338438
TI - Challenges in adult vaccination.
AB - Life-long primary prevention interventions beginning and continuing throughout an
individual's lifetime are increasingly seen as key to meeting the global
healthcare challenges that accompany demographic changes - a concept referred to
as "Healthy aging". In this perspective, vaccination is seen as part of a triad,
together with healthy diet and exercise. Current adult vaccine coverage is lower
than target vaccination rates in most developed countries, and so vaccine
preventable diseases continue to present a substantial burden on health and
healthcare resources, especially in older individuals. In part, this is due to
lack of knowledge and understanding of the benefits of vaccination, inconsistent
recommendations by providers and uncertainties about cost benefits. However,
lower vaccine effectiveness in older adults plays a part, and new vaccines with
novel characteristics to improve effectiveness in older adults are required. A
life-course immunization approach to ensure optimal vaccine uptake across adults
of all ages can be expected to reduce morbidity and mortality in later life. To
achieve this, greater emphasis on public and healthcare provider education is
necessary, based on appropriate economic analyses that demonstrate the overall
value of vaccination. This article introduces the technical, economic, political
and demographic issues that make establishing effective adult vaccination
programs such a difficult, but pressing issue, and outlines some of the steps
that are now being taken to address them. Key messages Life-long preventive
activities that start and continue throughout life are essential, especially as
the world's population is "getting older". This "Healthy aging" approach includes
not only healthy diet and physical exercise; vaccination is critical in reducing
some infectious diseases and their complications. Many adults, especially older
adults (who have lower immunity than younger people) develop infections such as
influenza and shingles that could potentially be prevented through vaccination.
This review provides a perspective on the challenges in delivering a life-course
immunization program. While some vaccines are less effective in older people,
newer vaccines have been developed which provide stronger and longer protection
in older patients than standard existing vaccines. However, the benefits of
vaccination can only be realized if the vaccines are recommended and used. For
that purpose, greater education of patients and their healthcare providers is
necessary. Better knowledge of vaccines and making sure that all adults are up to
date with all their recommended vaccines is an essential part of "Healthy aging".
This should prevent not only vaccine-preventable diseases but also reduce the
risk of complications in later life.
PMID- 29338437
TI - Elderly population have a decreased aneurysmal subarachnoid hemorrhage incidence
rate than Middle aged population: a descriptive analysis of 8,144 cases in
mainland China.
AB - PURPOSE: Rupture of an intracranial aneurysm is a life-threatening acute
cerebrovascular event. The purpose of this study was to investigate whether
aneurysmal subarachnoid haemorrhage (SAH) incidence rate is higher or lower in
elderly population than in middle aged population. MATERIALS AND METHODS:
Aneurysmal SAH cases were collected retrospectively from the archives of 21
hospitals in Mainland China. All the cases were collected from September 2016 and
backward consecutively for a period of time up to 8 years. SAH was initially
diagnosed by brain computed tomography (CT). CT angiography (CTA) or digital
subtraction angiography (DSA) was followed and SAH was confirmed to be due to
cerebral aneurysm rupture. For cases when multiple bleeding occurred, the age of
the first SAH was used in this study. The total incidence from all hospitals at
each age group were summed together for females and males respectively; then
adjusted by the total population number at each age group for females and males
which was from the 2010 population census of the People's Republic of China.
RESULTS: In total there were 8,144 cases of intracranial aneurysmal SAH, with
4,861 females and 3,283 males. For females the relative aneurysmal SAH incidence
rate started to decrease after around 65 years old, while for males the relative
aneurysmal SAH incidence rate started to decrease after around 53 years old.
CONCLUSION: Our data tentatively suggest elderly patients may be at a reduced
risk of rupture compared with patients who are younger while have similar other
risk factors.
PMID- 29338439
TI - Masterclass Education Program of the Clinical Coders' Society of Australia Ltd
(CCSA).
PMID- 29338441
TI - Across the Tasman and beyond.
PMID- 29338440
TI - Selective progesterone receptor modulators: current applications and
perspectives.
AB - Selective progesterone receptor modulators (SPRMs) are steroid progesterone
receptor ligands able to induce agonistic or antagonistic activities.
Mifepristone, the class leader, was primarily used for pregnancy termination from
the 1980s. Emergency contraception with extended activity was the second major
development 30 years later, with mifepristone in some countries and ulipristal
acetate world-wide. More recently, ulipristal acetate was released for the
treatment of myoma-related uterine bleeding. In addition to a very rapid
cessation of bleeding, SPRMs allow a decrease in myoma volume, as do gonadotropin
releasing hormone analogs. However, estradiol secretion is not blunted by SPRMs.
This offers new alternatives for myoma treatment, especially in women close to
menopause. In conclusion, use of SPRMs has allowed significant progress in
emergency contraception and treatment of myoma-related symptoms. Numerous future
perspectives in women's health care are currently under evaluation.
PMID- 29338442
TI - HIMAA Continuing Professional Development Planning Day.
PMID- 29338443
TI - Barriers to Acupuncture Use Among Breast Cancer Survivors: A Cross-Sectional
Analysis.
AB - INTRODUCTION: Increasing evidence suggests that acupuncture may be helpful to
manage common symptoms and treatment side effects among breast cancer (BC)
survivors. Acupuncture usage among BC survivors remains low with little known
about the barriers to its utilization. We evaluated perceived barriers to
acupuncture use among BC survivors and explored the sociodemographic variations
of such barriers. METHODS: We conducted a cross-sectional analysis at an urban
academic cancer center on 593 postmenopausal women with a history of stage I-III
hormone receptor-positive BC who were taking or had taken an aromatase inhibitor.
We used the modified Attitudes and Beliefs about Complementary and Alternative
Medicine instrument to evaluate patients' perceived barriers to acupuncture.
Multiple linear regression analysis was performed to determine sociodemographic
factors associated with perceived barrier scores. RESULTS: The most common
barriers were lack of knowledge about acupuncture (41.6%), concern for lack of
insurance coverage (25.0%), cost (22.3%), and difficulty finding qualified
acupuncturists (18.6%). Compared with whites, minority patients had higher
perceived barriers to use acupuncture (beta coefficient = 1.63, 95% confidence
interval = 0.3-2.9, P = .013). Patients with lower education had higher barriers
to use acupuncture (beta coefficient = 4.23, 95% confidence interval = 3.0-5.4, P
< .001) compared with patients with college education or above. CONCLUSION: Lack
of knowledge and concerns for insurance coverage and cost are the common barriers
to acupuncture use among BC survivors, especially among minority patients with
lower education. Addressing these barriers may lead to more equitable access to
acupuncture treatment for BC survivors from diverse backgrounds.
PMID- 29338444
TI - The First Approved Gene Therapy Product for Cancer Ad-p53 (Gendicine): 12 Years
in the Clinic.
AB - Gendicine (recombinant human p53 adenovirus), developed by Shenzhen SiBiono
GeneTech Co. Ltd., was approved in 2003 by the China Food and Drug Administration
(CFDA) as a first-in-class gene therapy product to treat head and neck cancer,
and entered the commercial market in 2004. Gendicine is a biological therapy that
is delivered via minimally invasive intratumoral injection, as well as by
intracavity or intravascular infusion. The wild-type (wt) p53 protein expressed
by Gendicine-transduced cells is a tumor suppressor that is activated by cellular
stress, and mediates cell-cycle arrest and DNA repair, or induces apoptosis,
senescence, and/or autophagy, depending upon cellular stress conditions. Based on
12 years of commercial use in >30,000 patients, and >30 published clinical
studies, Gendicine has exhibited an exemplary safety record, and when combined
with chemotherapy and radiotherapy has demonstrated significantly higher response
rates than for standard therapies alone. In addition to head and neck cancer,
Gendicine has been successfully applied to treat various other cancer types and
different stages of disease. Thirteen published studies that include long-term
survival data showed that Gendicine combination regimens yield progression-free
survival times that are significantly longer than standard therapies alone.
Although the p53 gene is mutated in >50% of all human cancers, p53 mutation
status did not significantly influence efficacy outcomes and long-term survival
rate for Ad-p53-treated patients. To date, Shenzhen SiBiono GeneTech has
manufactured 41 batches of Gendicine in compliance with CFDA QC/QA requirements,
and 169,571 vials (1.0 * 1012 vector particles per vial) have been used to treat
patients. No serious adverse events have been reported, except for vector
associated transient fever, which occurred in 50-60% of patients and persisted
for only a few hours. The manufacturing accomplishments and clinical experience
with Gendicine, as well as the understanding of its cellular mechanisms of action
and implications, could provide valuable insights for the international gene
therapy community and add valuable data to promote further developments and
advancements in the gene therapy field.
PMID- 29338445
TI - Investigational inhaled therapies for non-CF bronchiectasis.
AB - INTRODUCTION: Bronchiectasis not related to cystic fibrosis (non-CF
bronchiectasis) are associated with a high unmet therapeutic need due to the lack
of specifically authorized medications, especially via the inhalation route. In
non-CF bronchiectasis chronic infection with Pseudomonas aeruginosa is common and
favored by the persistent local inflammation and viscid sputum production.
Therefore inhaled antibiotics, mucolytics or anti-inflammatory agents could
represent appropriate therapeutic interventions in this setting Areas covered:
This review herein discusses the inhaled therapies currently under investigation
for non-CF bronchiectasis and their potential therapeutic positioning in
exacerbation versus stable state. Expert opinion: Inhaled antipseudomonal
antibiotics are of promising efficacy, but further efforts should also be made to
detect bactericidal approaches against Burkholderia cepacia complex, and to
interfere chronic inflammation topically.
PMID- 29338446
TI - The latest animal models of ovarian cancer for novel drug discovery.
AB - INTRODUCTION: Epithelial ovarian cancer is a heterogeneous disease classified
into five subtypes, each with a different molecular profile. Most cases of
ovarian cancer are diagnosed after metastasis of the primary tumor and are
resistant to traditional platinum-based chemotherapeutics. Mouse models of
ovarian cancer have been utilized to discern ovarian cancer tumorigenesis and the
tumor's response to therapeutics. Areas covered: The authors provide a review of
mouse models currently employed to understand ovarian cancer. This article
focuses on advances in the development of orthotopic and patient-derived tumor
xenograft (PDX) mouse models of ovarian cancer and discusses current humanized
mouse models of ovarian cancer. Expert opinion: The authors suggest that
humanized mouse models of ovarian cancer will provide new insight into the role
of the human immune system in combating and augmenting ovarian cancer and aid in
the development of novel therapeutics. Development of humanized mouse models will
take advantage of the NSG and NSG-SGM3 strains of mice as well as new strains
that are actively being derived.
PMID- 29338447
TI - Changes to the ACHS Evaluation and Quality Improvement Program (EQuIP) Standards
for Information Management.
PMID- 29338449
TI - Operation Zipit! Privacy is a Hot Topic!
PMID- 29338448
TI - The safety of palbociclib for the treatment of advanced breast cancer.
AB - INTRODUCTION: Despite improvements in the diagnosis and management of early stage
breast cancer, about one third of the patients still progress to metastatic
disease. Most of the patients with metastatic breast cancer have a hormone
receptor positive and human epidermal growth factor receptor 2 negative subtype
with a median survival of more than 3 years. For these patients, endocrine
therapy with its favorable toxicity profile is the current standard of care.
However, patients with metastatic breast cancer have an incurable disease.
Therefore, not only efficacy but also quality of life are key when selecting a
therapy regimen. Areas covered: This paper aims to discuss the efficacy and
toxicity profile of the new endocrine-based therapy option palbociclib together
with endocrine treatment. Expert opinion: The addition of targeted agents like
palbociclib can overcome intrinsic or acquired resistance to endocrine therapy
and substantially prolong progression free survival. The combination of
palbociclib plus endocrine therapy is associated with a tolerable and well
manageable toxicity profile as well as maintenance of quality of life. Thus,
addition of palbociclib to endocrine therapy offers a new and important treatment
option for hormone receptor positive metastatic breast cancer.
PMID- 29338450
TI - How can primary care physicians enhance the early diagnosis of rheumatic
diseases?
PMID- 29338451
TI - The Use of Clinical Classifications in the Nordic Countries.
AB - This article gives an overview of the current use of the main clinical
classifications in the Nordic countries. A brief introduction describes the
background and content of Nordic co-operation in the areas of health statistics
and health-related classifications. The use of the current international
classifications is well established in the Nordic countries. Some Nordic
classifications have been developed in co-operation with maintenance and updating
performed as a joint Nordic responsibility.
PMID- 29338452
TI - An update on diagnostic and prognostic biomarkers for traumatic brain injury.
AB - INTRODUCTION: Traumatic brain injury (TBI) is a major worldwide neurological
disorder of epidemic proportions. To date, there are still no FDA-approved
therapies to treat any forms of TBI. Encouragingly, there are emerging data
showing that biofluid-based TBI biomarker tests have the potential to diagnose
the presence of TBI of different severities including concussion, and to predict
outcome. Areas covered: The authors provide an update on the current knowledge of
TBI biomarkers, including protein biomarkers for neuronal cell body injury (UCH
L1, NSE), astroglial injury (GFAP, S100B), neuronal cell death (alphaII-spectrin
breakdown products), axonal injury (NF proteins), white matter injury (MBP), post
injury neurodegeneration (total Tau and phospho-Tau), post-injury autoimmune
response (brain antigen-targeting autoantibodies), and other emerging non-protein
biomarkers. The authors discuss biomarker evidence in TBI diagnosis, outcome
prognosis and possible identification of post-TBI neurodegernative diseases (e.g.
chronic traumatic encephalopathy and Alzheimer's disease), and as theranostic
tools in pre-clinical and clinical settings. Expert commentary: A spectrum of
biomarkers is now at or near the stage of formal clinical validation of their
diagnostic and prognostic utilities in the management of TBI of varied severities
including concussions. TBI biomarkers could serve as a theranostic tool in
facilitating drug development and treatment monitoring.
PMID- 29338453
TI - Proteomic serum biomarkers for neuromuscular diseases.
AB - INTRODUCTION: The clinical evaluation of neuromuscular symptoms often includes
the assessment of altered blood proteins or changed enzyme activities. However,
the blood concentration of many muscle-derived serum markers is not specific for
different neuromuscular disorders and also shows alterations in the course of
these diseases. Thus, the establishment of more reliable biomarker signatures for
improved muscle diagnostics is required. Areas covered: To address the lack of
muscle disease-specific marker molecules, mass spectrometry-based proteomics was
applied to the systematic identification and biochemical characterization of new
serum biomarker candidates. This article outlines serum proteomics in relation to
neuromuscular disorders and reviews the bioanalytical results from recent
proteomic profiling studies of representative neuromuscular disorders, including
motor neuron disease, muscular dystrophies and sarcopenia of old age.
Pathophysiological changes in the skeletal muscle proteome are reflected by serum
alterations in a variety of sarcomeric proteins, metabolic enzymes and signaling
proteins. Expert commentary: Based on the proteomic identification of actively
secreted or passively released skeletal muscle proteins following
pathophysiological insults, new biomarker candidates can now be used to develop
liquid biopsy procedures for superior diagnostic approaches, design novel
prognostic tools and establish more reliable methods for the systematic
evaluation of experimental therapies to treat neuromuscular disease.
PMID- 29338455
TI - Current treatment options for meningioma.
AB - INTRODUCTION: With an annual incidence of 5/100,000, meningioma is the most
frequent primary tumor of the central nervous system. Risk factors are
radiotherapy and hormone intake. Most meningiomas are grade I benign tumors, but
up to 15% are atypical and 2% anaplastic according to the WHO 2016 histological
criteria. Areas covered: This review details the current standard therapy based
on international guidelines and recent literature, and describes new approaches
developed to treat refractory cases. First-line treatments are observation and
surgery, but adjuvant radiotherapy/radiosurgery is discussed for atypical and
indicated for anaplastic meningiomas. The most problematic cases include skull
base meningiomas that enclose vasculo-nervous structures and surgery- and
radiation-refractory tumors that present with significant morbidity and
mortality. The treatment of recurrent tumors is based on radiotherapy and
repeated surgery. Systematic therapies are not effective in general but several
clinical trials are ongoing. Expert commentary: Molecular characterization of the
tumors, based on genetic mutations such as NF2, SMO, TERT, TRAF7, and on the
methylation profile are developing, completing the histological classification
and giving new insights into prognosis and treatment options.
PMID- 29338457
TI - What Role Should HIMAA Take in the Continuing Professional Development (CPD) of
Health Information Managers?
PMID- 29338454
TI - Chemical, computational and functional insights into the chemical stability of
the Hedgehog pathway inhibitor GANT61.
AB - This work aims at elucidating the mechanism and kinetics of hydrolysis of GANT61,
the first and most-widely used inhibitor of the Hedgehog (Hh) signalling pathway
that targets Glioma-associated oncogene homologue (Gli) proteins, and at
confirming the chemical nature of its bioactive form. GANT61 is poorly stable
under physiological conditions and rapidly hydrolyses into an aldehyde species
(GANT61-A), which is devoid of the biological activity against Hh signalling, and
a diamine derivative (GANT61-D), which has shown inhibition of Gli-mediated
transcription. Here, we combined chemical synthesis, NMR spectroscopy, analytical
studies, molecular modelling and functional cell assays to characterise the
GANT61 hydrolysis pathway. Our results show that GANT61-D is the bioactive form
of GANT61 in NIH3T3 Shh-Light II cells and SuFu-/- mouse embryonic fibroblasts,
and clarify the structural requirements for GANT61-D binding to Gli1. This study
paves the way to the design of GANT61 derivatives with improved potency and
chemical stability.
PMID- 29338456
TI - An update on the safety of nutraceuticals and effects on lipid parameters.
AB - INTRODUCTION: Cardiovascular diseases (CVDs) are the leading cause of mortality
and disability in developed countries, whereas a large portion of patients in
primary prevention have uncontrolled level of CVD risk factors. Dietary
supplementation with bioactive natural compounds with demonstrated lipid-lowering
effects is currently supported by the international guidelines for CVD prevention
and some international expert panels. Areas covered: This review provides
insights on issues concerning the tolerability and safety of the most commonly
used nutraceuticals with demonstrated lipid-lowering effect in humans. They will
be then divided into three main categories according to their mechanism of action
(cholesterol synthesis inhibitors, intestinal cholesterol absorption inhibitors,
and LDL-C excretion stimulants) and their pharmacological profile will be
discussed. Expert opinion: A growing body of preclinical, epidemiological and
clinical evidence has defined the tolerability and safety profile of the most
commonly used lipid-lowering nutraceuticals. In the most part of cases, the side
effects are mild and reversible. However, detailed knowledge of specific health
risks and pharmacological interactions for each individual compound is needed for
the management of frail patients, such as children, elderly, patients with liver
or renal failure, and patients consuming numerous drugs.
PMID- 29338458
TI - Tenofovir alafenamide (TAF) treatment of HBV, what are the unanswered questions?
AB - INTRODUCTION: Tenofovir disoproxil fumarate (TDF), an ester prodrug of tenofovir
(TFV), is one of the recommended drugs for chronic hepatitis B (CHB) patients.
However, reduced kidney function and loss of bone mineral density have been
reported in some CHB patients treated with TDF. Consequent to these safety
issues, tenofovir alafenamide (TAF) [Vemlidy(r)], a phosphonate prodrug of TFV,
was developed for the treatment of CHB patients. Areas covered: The favourable
pharmacological profile of TAF allows a marked reduction in dosage (25 mg/day)
thus reducing systemic exposure to tenofovir and improving the bone and renal
safety, keeping however the same virological efficacy, compared to TDF 300
mg/day. In two ongoing 96-week phase III trials in mainly treatment-naive HBeAg
positive or -negative patients, TAF showed similar viral suppression but was
associated with significantly higher alanine aminotransferase normalization rates
and more favourable renal and bone safety compared to TDF. In a 48-week TAF
switch study enrolling patients treated with TDF for 96 weeks, glomerular,
tubular and bone safety parameters rapidly improved while virological suppression
was maintained. Expert commentary: Waiting long-term large scale clinical
practice studies aimed to confirm these advantages, TAF represents an helpful
treatment option for both naive and TDF-exposed CHB patients.
PMID- 29338460
TI - Research in Health Information Management.
PMID- 29338459
TI - An interprofessional collaborative practice approach to transform heart failure
care: An overview.
AB - Interprofessional collaborative practice (IPCP) approaches to health care are
increasingly recognized as necessary to achieve the Triple Aim-improved health of
the population, improved patient care experience, and improved affordability of
care. This paper introduces and provides an overview of an interprofessional
intervention to improve a healthcare team, healthcare system, and patient
outcomes for hospitalized patients with heart failure. In this paper, we describe
the overall project resulting from a workforce training grant and the proposed
series of future papers resulting from the interprofessional intervention.
Collectively, these papers will describe the results of a unique IPCP approach on
team, system, and patient outcomes as well as describe and compare organizational
and leadership traits that affect collaborative practice. Our hope is that the
intervention approaches, evaluation results, and lessons learned described in
these papers will help further the efforts to spread IPCP approaches to
transforming health care.
PMID- 29338461
TI - mTOR dysregulation and tuberous sclerosis-related epilepsy.
AB - INTRODUCTION: The mammalian target of rapamycin (mTOR) pathway has emerged as a
key player for proper neural network development, and it is involved in
epileptogenesis triggered by both genetic or acquired factors. Areas covered. The
robust mTOR signaling deregulation observed in a large spectrum of epileptogenic
developmental pathologies, such as focal cortical dysplasias and tuberous
sclerosis complex (TSC), has been linked to germline and somatic mutations in
mTOR pathway regulatory genes, increasing the spectrum of 'mTORopathies'. The
significant advances in the field of TSC allowed for the validation of emerging
hypotheses on the mechanisms of epileptogenesis and the identification of
potential new targets of therapy. Recently, a double-blind phase III randomized
clinical trial on patients with TSC related epilepsy, demonstrated that
adjunctive treatment with mTOR inhibition is effective and safe in reducing focal
drug resistant seizures. Expert commentary. mTOR signaling dysregulation
represents a common pathogenic mechanism in a subset of malformations of cortical
development, sharing histopathological and clinical features, including epilepsy,
autism, and intellectual disability. EXIST-3 trial provided the first evaluation
of the optimal dosage, conferring a higher chance of reducing seizure frequency
and severity, with adverse events being similar to what observed with lower
dosages.
PMID- 29338463
TI - Cattanach v Melchior and Implications for Health Information Managers.
PMID- 29338462
TI - Rethinking revascularization in patients with stable angina.
AB - INTRODUCTION: Traditional and current perception for benefit of percutaneous
coronary intervention (PCI) is that patients with stable angina will obtain
symptom relief as well as improved exercise capacity after percutaneous
revascularization. This common clinical perception is put to test in the ORBITA
trial, the first blinded, randomized placebo-controlled clinical study ever
conducted.Areas covered: Coronary artery disease, percutaneous coronary
intervention, medical therapy.Expert Commentary: The authors found no significant
improvement in exercise time, functional status, angina relief and quality of
life in the PCI group compared with placebo. A possible explanation for this
neutral outcome is that PCI is overvalued in symptom relief and to some extent
explained by placebo effects or transient non-cardiac causes of chest pain.
However, the chosen exercise tolerance improvement may have been too optimistic
in a population with good functional capacity. Also PCI was anatomic and not
functional driven, and follow-up duration may have been to short to wear off the
placebo effect. While the evidence is not sufficient to alter revascularization
guidelines, the message of this 200-patient, high-quality study is potent and
will reverberate throughout the cardiology community and warrants further study.
PMID- 29338464
TI - Hearing aid technology: model-based concepts and assessment.
PMID- 29338465
TI - Standards: Flag Waving or Marking the Foundations?
PMID- 29338466
TI - Valbenazine as the first and only approved treatment for adults with tardive
dyskinesia.
AB - INTRODUCTION: Valbenazine is a selective VMAT2 inhibitor that the FDA approved in
April 2017 for the specific treatment of tardive dyskinesia (TD), a movement
disorder commonly caused by dopamine blocking agents. Valbenazine acts to
decrease dopamine release, reducing excessive movement found in TD. Areas
covered: This drug profile reviews the development of valbenazine and the
clinical trials that led to its approval as the first treatment specific to TD.
The literature search was performed with the PubMed online database. Expert
commentary: Two clinical trials assessing the efficacy of valbenazine have shown
the reduction of antipsychotic-induced involuntary movement. No life threatening
adverse effects were found. Data from a 42-week extension study demonstrated
sustained response.
PMID- 29338467
TI - The Pharmacy Management Information System at the Department of Veterans'
Affairs.
AB - This article describes the pharmacy management information systems environment
currently being implemented at the Australian Department of Veterans' Affairs
(DVA), and focuses on the objectives and design of the medication management
program's management of information. As the system is new, it is too early to
predict the difference that it will make to the operations and policy initiatives
within the Medication Management section. The anticipated benefits are discussed.
The user reaction, and the uses of these management data, are part of an ongoing
benefits realisation study and the subject of a future article.
PMID- 29338468
TI - Inhibition of the proteasome activity by graphene oxide contributes to its
cytotoxicity.
AB - Due to its hydrophobicity and other unique physicochemical properties, graphene
oxide (GO) has been extensively utilized in various biological applications.
However, introducing nanomaterials into the biological environment may raise
serious risk in terms of nanotoxicity, leading to some unintended changes to the
structure and the function of other biomolecules. This study investigates the
interaction of GO with the ubiquitin-proteasome system, one of the essential
machineries in the cellular metabolism, using a combination of experimental and
computational approaches. The experimental results show that GO could adsorb the
20S proteasome, causing a dose-dependent suppression of the proteolytic activity
of proteasome. This adverse effect eventually disturbed other important cellular
activities relevant to cell cycle and survival. Meanwhile, the molecular dynamics
simulations revealed that when 20S proteasome was adsorbed onto the graphene
surface, the central gate in the outer ring (alpha-subunit) for the entry and the
exit of the peptide ligand to the protease active site was effectively blocked.
These findings of GO induced functional disturbance of 20S proteasome provides a
novel perspective to understand the molecular mechanism of GO's cytotoxicity,
which might further promote applications of GO in potential therapies for various
cancers due to the abnormal elevation of the relevant proteasome activities.
PMID- 29338469
TI - Assessing efficacy of day 3 embryo time-lapse algorithms retrospectively: impacts
of dataset type and confounding factors.
AB - This study investigated the efficacy of four published day 3 embryo time-lapse
algorithms based on different types of datasets (known implantation data [KID]
and single embryo transfer [SET]), and the confounding effect of female age and
conventional embryo morphology. Four algorithms were retrospectively applied to
three types of datasets generated at Fertility North between February 2013 and
December 2014: (a) KID dataset (n = 270), (b) a subset of SET (n = 144, end-point
= implantation), and (c) SET (n = 144, end-point = live birth), respectively. All
four algorithms showed progressively reduced predictive power (expressed as area
under the receiver operating characteristics curve and 95% confidence interval
[CI]) after application to the three datasets (a-c): Liu (0.762 [0.701-0.824] vs.
0.724 [0.641-0.807] vs. 0.707 [0.620-0.793]), KIDScore (0.614 [0.539-0.688] vs.
0.548 [0.451-0.645] vs. 0.536 [0.434-0.637]), Meseguer (0.585 [0.508-0.663] vs.
0.56 [0.462-0.658] vs. 0.549 [0.445-0.652]), and Basile (0.582 [0.505-0.659] vs.
0.519 [0.421-0.618] vs. 0.509 [0.406-0.612]). Furthermore, using KID dataset, the
association (expressed as odds ratio and 95% CI) between time-lapse algorithms
and implantation outcomes lost statistical significance after adjusting for
conventional embryo morphology and female age in 3 of the 4 algorithms (KIDScore
1.832 [1.118-3.004] vs. 1.063 [0.659-1.715], Meseguer 1.150 [1.021-1.295] vs.
1.122 [0.981-1.284] and Basile 1.122 [1.008-1.249] vs. 1.038 [0.919-1.172]). In
conclusion, SET is a preferred dataset to KID when developing or validating time
lapse algorithms, and day 3 conventional embryo morphology and female age should
be considered as confounding factors.
PMID- 29338470
TI - Measurement error in the Liebowitz Social Anxiety Scale: results from a general
adult population in Japan.
AB - OBJECTIVE: Although the self-report version of Liebowitz Social Anxiety Scale
(LSAS) is frequently used to measure social anxiety, data is lacking on the
smallest detectable change (SDC), an important index of measurement error. We
therefore aimed to determine the SDC of LSAS. METHODS: Japanese adults aged 20-69
years were invited from a panel managed by a nationwide internet research agency.
We then conducted a test-retest internet survey with a two-week interval to
estimate the SDC at the individual (SDCind) and group (SDCgroup) levels. RESULTS:
The analysis included 1300 participants. The SDCind and SDCgroup for the total
fear subscale (scoring range: 0-72) were 23.52 points (32.7%) and 0.65 points
(0.9%), respectively. The SDCind and SDCgroup for the total avoidance subscale
(scoring range: 0-72) were 32.43 points (45.0%) and 0.90 points (1.2%),
respectively. The SDCind and SDCgroup for the overall total score (scoring range:
0-144) were 45.90 points (31.9%) and 1.27 points (0.9%), respectively.
CONCLUSIONS: Measurement error is large and indicate the potential for major
problems when attempting to use the LSAS to detect changes at the individual
level. These results should be considered when using the LSAS as measures of
treatment change.
PMID- 29338472
TI - AHIMA Today.
PMID- 29338471
TI - Transjugular intrahepatic portosystemic stent shunt placement and embolization
for hemorrhage associated with rupture of anorectal varices.
AB - Portal hypertension can lead to ectopic varices, which occur most frequently in
the rectum. Rectal variceal bleeding in patients with portal hypertension is rare
but can be life-threatening if not diagnosed and treated in a timely manner.
However, no specific treatment guidelines have been established for rectal
variceal bleeding. We herein report a case involving a woman with portal
hypertension due to autoimmune liver disease who was successfully treated with a
transjugular intrahepatic portosystemic stent shunt and variceal embolization. We
recommend treatment of refractory ectopic variceal bleeding with a transjugular
intrahepatic portosystemic stent shunt in combination with embolization.
PMID- 29338473
TI - Phylogenomics of tomato chloroplasts using assembly and alignment-free method.
AB - Phylogenetics and population genetics are central disciplines in evolutionary
biology. Both are based on the comparison of single DNA sequences, or a
concatenation of a number of these. However, with the advent of next-generation
DNA sequencing technologies, the approaches that consider large genomic data sets
are of growing importance for the elucidation of evolutionary relationships among
species. Among these approaches, the assembly and alignment-free methods which
allow an efficient distance computation and phylogeny reconstruction are of great
importance. However, it is not yet clear under what quality conditions and
abundance of genomic data such methods are able to infer phylogenies accurately.
In the present study we assess the method originally proposed by Fan et al. for
whole genome data, in the elucidation of Tomatoes' chloroplast phylogenetics
using short read sequences. We find that this assembly and alignment-free method
is capable of reproducing previous results under conditions of high coverage,
given that low frequency k-mers (i.e. error prone data) are effectively filtered
out. Finally, we present a complete chloroplast phylogeny for the best data
quality candidates of the recently published 360 tomato genomes.
PMID- 29338474
TI - Subarachnoid space diameter in chromosomally abnormal fetuses at 11-13 weeks'
gestation.
AB - OBJECTIVES: To examine the subarachnoid space diameters in chromosomally abnormal
fetuses at 11-13 weeks' gestation. METHODS: Stored three-dimensional (3D)
ultrasound volumes of the fetal head at 11-13 weeks' gestation from 407 euploid
and 88 chromosomally abnormal fetuses (trisomy 21, n = 40; trisomy 18, n = 19;
trisomy 13, n = 7; triploidy, n = 14; Turner syndrome, n = 8) were analyzed. The
subarachnoid space diameters, measured in the sagittal and transverse planes of
the fetal head, in relation to biparietal diameter (BPD) in each group of
aneuploidies was compared to that in euploid fetuses. A total of 20 head volumes
were randomly selected and all the measurements were recorded by two different
observers to examine the interobserver variability in measurements. RESULTS: In
euploid fetuses, the anteroposterior, transverse and sagittal diameters of the
subarachnoid space increased with BPD. The median of the observed to expected
diameters for BPD were significantly increased in triploidy and trisomy 13 but
were not significantly altered in trisomies 21 and 18 or Turner syndrome. In
triploidy, the subarachnoid space diameters for BPD were above the 95th centile
of euploid fetuses in 92.9% (13 of 14) cases. The intraclass reliability or
agreement was excellent for all three subarachnoid space diameters. CONCLUSION:
Most fetuses with triploidy at 11-13 weeks' gestation demonstrate increased
subarachnoid space diameters.
PMID- 29338475
TI - Advances in atrioventricular and interventricular optimization of cardiac
resynchronization therapy - what's the gold standard?
AB - INTRODUCTION: Cardiac resynchronization therapy (CRT) is one of the most
important advances in heart failure management in the last twenty years.
Approximately one-third of patients appear not to respond to therapy. Although
there are a number of possible mechanisms for non-response, an important factor
is suboptimal atrioventricular (AV) and interventricular (VV) timing intervals.
There remains controversy over whether routinely optimizing intervals is
necessary and there is no agreed gold standard methodology. Optimization has
classically been performed using echocardiography which has limits related to
resource use, time-cost and variable reproducibility. Newer optimization methods
using device-based sensors and algorithms show promise in reducing heart-failure
hospitalization compared with echocardiography. Areas covered: This review
outlines the rationale for optimization, the principles of AV and VV
optimization, the standard echocardiographic approach and newer device-based
algorithms and the evidence base for their use. Expert commentary: The
incremental gains of optimization are likely to be real, but small, compared to
the overall improvement gained from cardiac resynchronization itself. At this
time routine optimization may not be mandatory but should be performed where
there is no response to CRT. Device-based optimization algorithms appear to be
practical and in some cases, deliver superior clinical outcomes compared to
echocardiography.
PMID- 29338476
TI - Evaluation and efficacy of carbon dioxide therapy (carboxytherapy) versus
mesolipolysis in the treatment of cellulite.
AB - BACKGROUND: Cellulite is an irregular alteration of the skin surface giving it
cottage cheese appearance. Carboxytherapy is transcutaneous infusion of carbon
dioxide into the affected site. Mesolipolysis aims to remove cellulite and
improve skin texture. AIMS: To verify the efficacy and safety of carboxytherapy
versus mesolipolysis using phosphatidylcholine (PPC) in treatment of cellulite in
thighs area. METHODS: Forty-eight female patients with different grades of
cellulite at thighs area were enrolled in this study. They were classified into
two groups: group A received subcutaneous infusion of carboxytherapy, and group B
was treated with mesolipolysis using PPC. Each group received six sessions at
weekly intervals. sessions. The outcome measures and clinical assessment were
based on cellulite grading scale and thigh circumference measurements.
Standardized digital photography was taken before and after treatment. Patients
were followed up for 6 months. RESULTS: After treatment, there was significant
reduction in thigh circumference measurement p < 0.01 and cellulite grading scale
p < 0.001 in both groups. The difference in cellulite grading scale and thigh
circumference measurement in both groups was insignificant. CONCLUSIONS:
Carboxytherapy and mesolipolysis are safe and effective in cellulite treatment.
Carboxytherapy is a promising alternative therapeutic modality for cellulite
treatment.
PMID- 29338477
TI - Let the Race Begin!
PMID- 29338478
TI - Gene-gene-environment interactions of prenatal exposed to environmental tobacco
smoke, CYP1A1 and GSTs polymorphisms on full-term low birth weight: relationship
of maternal passive smoking, gene polymorphisms, and FT-LBW.
AB - OBJECTIVE: To examine the interaction effects of prenatal exposed to
environmental tobacco smoke (ETS) and genotypes of cytochrome P4501A1 (CYP1A1),
glutathione S-transferases (GSTs) on the risk of full-term low birth weight (FT
LBW). STUDY DESIGN: We conducted a case-control study among pregnant women at two
Women and Children's Hospitals in Guangdong, China (n = 910). Information was
collected through interview, medical records review, and blood lab tests.
Maternal selfreport and serum cotinine concentration were combined to define
prenatal exposed to ETS. Logistic regression approach was applied for statistical
analysis. RESULTS: Our results showed that regardless of genotypes, prenatal
exposed to ETS significantly increased the risk of FT-LBW. Then, two-way
interactions showed increased prevalence of FT-LBW in prenatal exposed to ETS
mothers with the CYP1A1 variant genotype (MspI "CC"), or with GSTT1-null
genotype. Furthermore, three-way interactions showed that women with CYP1A1
variant (MspI "TC" or BsrDI "AG") genotypes and GSTT1 "null" genotype had higher
risk to give birth of FT-LBW. Additionally, among nonexposed ETS mothers,
genotype did not independently confer adverse effects on FT-LBW. CONCLUSIONS: Our
results revealed that prenatal exposed to ETS is independently associated with FT
LBW while gene polymorphisms of CYP1A1 and GSTs merely play modified roles in
this process. This study extends understanding of three-way interaction, and
stresses the need to tobacco control toward pregnant women for better pregnant
outcomes.
PMID- 29338479
TI - Graphene oxide regulates cox2 in human embryonic kidney 293T cells via epigenetic
mechanisms: dynamic chromosomal interactions.
AB - To extend the applications of engineered nanomaterials, such as graphene oxide
(GO), it is necessary to minimize cytotoxicity. However, the mechanisms
underlying this cytotoxicity are unclear. Dynamic chromosomal interactions have
been used to illustrate the molecular bases of gene expression, which offers a
more sensitive and cutting-edge technology to elucidate complex biological
processes associated with epigenetic regulations. In this study, the role of GO
triggered chromatin interactions in the activation of cox2, a hallmark of
inflammation, was investigated in normal human cells. Using chromosome
conformation capture technology, we showed that GO triggers physical interactions
between the downstream enhancer and the cox2 promoter in human embryonic kidney
293T (293T) via p65 and p300 complex-mediated dynamic chromatin looping, which
was required for high cox2 expression. Moreover, tumor necrosis factor-alpha (TNF
alpha), located upstream of the p65 signaling pathway, contributed to the
regulation of cox2 activation through dynamic chromatin architecture. Compared
with pristine GO and aminated GO (GO-NH2), poly (acrylic acid)-functionalized GO
(GO-PAA) induced a weaker inflammatory response and a weaker effect on chromatin
architecture. Our results mechanistically link GO-mediated chromatin interactions
with the regulation of cox2 and suggest that GO derivatives may minimize toxicity
in practical applications.
PMID- 29338480
TI - The role of screening mammography in the era of modern breast cancer treatment.
AB - The evidence is reviewed on the efficacy and effectiveness of mammography
screening derived from randomized screening trials and from the surveillance of
populations where mammography screening for breast cancer has been introduced.
Nearly all the trials were performed in the era before modern adjuvant therapy
for breast cancer was introduced, apart from the Canadian National Breast
Screening Study and the UK Age trial. The former found no benefit from annual
mammography screening for 5 years in women age 40-59 years, the latter, a non
significant benefit from screening women by annual mammography for 7 years from
ages 39 to 41 years. The evidence from population-based surveillance is mixed,
most such studies having failed to consider the benefit gained from improved
therapy. It is concluded that we have reached the point of negligible benefit
from mammography screening for breast cancer in women at average risk, and that
we should concentrate on early diagnosis of breast cancer and the application of
modern therapy according to clearly defined sub-types of breast cancer.
PMID- 29338481
TI - Statement of retraction.
PMID- 29338483
TI - Reply to: Prehospital Intubation: Further Confounders in Trial Results.
PMID- 29338484
TI - The association between micronucleus, nucleoplasmic bridges, and nuclear buds
frequency and the degree of uterine cervical lesions.
AB - BACKGROUND AND AIM: The loss of genomic stability plays an important role in
carcinogenesis. Therefore, it is imperative to use certain biomarkers of DNA
damage due to genomic instability in order to predict cancer risk. The aim of
this study was the evaluation of genomic instability in patients with cervical
lesions. MATERIALS AND METHODS: We investigated the genetic damages in 80
subjects: 40 patients with high-grade squamous intraepithelial lesions (HSIL), 20
patients with invasive squamous cervical cancer (SCC) and 20 healthy women with a
biomarker in two different tissues; the micronucleus (MN) test in peripheral
blood lymphocytes (PBL), and in buccal exfoliated cells (BEC). This study also
examined the frequency of other nuclear anomalies such as nucleoplasmic bridges
(NPBs) and nuclear bunds (NBUDs) in PBL. RESULTS: The frequency of MN in BEC, MN
in PBL, NPB in PBL and NBUD in PBL were significantly higher (p < 0.001), in
patients compared to controls. The DNA damages in BEC and PBL were correlated
positively with histological grade of cervical lesions. CONCLUSION: Although
larger studies are needed, our data support the predictive value of MN, NPB and
NBUD as biomarkers of genomic instability for evaluation of risk level of cancer
diseases.
PMID- 29338485
TI - The Australian Coding Standards Advisory Committee.
PMID- 29338486
TI - Rewarding effects of physical activity predict sensitivity to the acute
subjective effects of d-amphetamine in healthy volunteers.
AB - While individual differences in reward sensitivity are believed to generalize
across drugs and alternative rewards, this notion has received little empirical
attention in human research. Here, we tested whether individual differences in
the subjective rewarding effects of physical activity were associated with the
subjective response to d-amphetamine administration. Healthy volunteers ( n=95;
age 18-35 years) completed questionnaires measuring the self-reported pleasurable
effects of physical activity and other covariates, and this was followed by two
double-blind counterbalanced sessions during which they received either 20 mg
oral d-amphetamine or placebo. Subjective drug effects measures were collected
before and repeatedly after drug administration. Subjective d-amphetamine-related
effects were then reduced via principal components analysis into latent factors
of "positive mood," "arousal," and "drug high." Multiple regression models
controlling for placebo-related scores, session order, demographics, body mass
index, level of physical activity, and use of other drugs showed that degree of
self-reported physical activity reward was positively associated with d
amphetamine-induced positive mood and arousal ( betas>=0.25, ps<=0.04), but was
not associated with d-amphetamine-induced changes in drug high ( beta=0.13,
p=0.24). These results provide novel evidence suggesting that individual
differences in reward sensitivity cross over between d-amphetamine reward and
physical activity reward in humans.
PMID- 29338488
TI - Macrophage polarization and activation at the interface of multi-walled carbon
nanotube-induced pulmonary inflammation and fibrosis.
AB - Pulmonary exposure to carbon nanotubes (CNTs) induces fibrosing lesions in the
lungs that manifest rapid-onset inflammatory and fibrotic responses, leading to
chronic fibrosis in animals and health concerns in exposed humans. The mechanisms
underlying CNT-induced fibrogenic effects remain undefined. Macrophages are known
to play important roles in immune regulation and fibrosis development through
their distinct subsets. Here we investigated macrophage polarization and
activation in mouse lungs exposed to multi-walled CNTs (MWCNTs). Male C57BL/6J
mice were treated with MWCNTs (XNRI MWNT-7) at 40 MUg per mouse (~1.86 mg/kg body
weight) by oropharyngeal aspiration. The treatment stimulated prominent acute
inflammatory and fibrotic responses. Moreover, it induced pronounced enrichment
and polarization of macrophages with significantly increased M1 and M2
populations in a time-dependent manner. Induction of M1 polarization was apparent
on day 1 with a peak on day 3, but declined rapidly thereafter. On the other
hand, the M2 polarization was induced on day 1 modestly, but was remarkably
elevated on day 3 and maintained at a high level through day 7. M1 and M2
macrophages were functionally activated by MWCNTs as indicated by the expression
of their distinctive functional markers, such as iNOS and ARG1, with time courses
parallel to M1 and M2 polarization, respectively. Molecular analysis revealed
MWCNTs boosted specific STAT and IRF signaling pathways to regulate M1 and M2
polarization in the lungs. These findings suggest a new mechanistic connection
between inflammation and fibrosis induced by MWCNTs through the polarization and
activation of macrophages during MWCNT-induced lung pathologic response.
PMID- 29338487
TI - Acupuncture treatments for infantile colic: a systematic review and individual
patient data meta-analysis of blinding test validated randomised controlled
trials.
AB - OBJECTIVE: Needle acupuncture in small children has gained some acceptance in
Western medicine. It is controversial, as infants and toddlers are unable to
consent to treatment. We aimed to assess its efficacy for treating infantile
colic. DESIGN: A systematic review and a blinding-test validation based on
individual patient data from randomised controlled trials. Primary end-points
were crying time at mid-treatment, at the end of treatment and at a 1-month
follow-up. A 30-min mean difference (MD) in crying time between acupuncture and
control was predefined as a clinically important difference. Pearson's chi
squared test and the James and Bang indices were used to test the success of
blinding of the outcome assessors [parents]. Eligibility criteria and data
sources: We included randomised controlled trials of acupuncture treatments of
infantile colic. Systematic searches were conducted in Cochrane CENTRAL, MEDLINE,
EMBASE, CINAHL and AMED, and in the Chinese language databases CNKI, VIP, Wang
fang, SinoMed and Chinese Clinical Trial Registry. RESULTS: We included three
randomised controlled trials with data from 307 participants. Only one of the
included trials obtained a successful blinding of the outcome assessors in both
the acupuncture and control groups. The MD in crying time between acupuncture
intervention and no acupuncture control was -24.9 min [95% confidence interval,
CI -46.2 to -3.6; three trials] at mid-treatment, -11.4 min [95% CI -31.8 to 9.0;
three trials] at the end of treatment and -11.8 min [95% CI -62.9 to 39.2; one
trial] at the 4-week follow-up. The corresponding standardised mean differences
[SMDs] were -0.23 [95% CI -0.42 to -0.06], -0.10 [95% CI -0.29 to 0.08] and -0.09
[95% CI -0.48 to 0.30]. The heterogeneity was negligible in all analyses. The
statistically significant result at mid-treatment was lost when excluding the
apparently unblinded study in a sensitivity analysis: MD -13.8 min [95%CI -37.5
to 9.9] and SMD -0.13 [95%CI -0.35 to 0.09]. The registration of crying during
treatment suggested more crying during acupuncture [odds ratio 7.7; 95% CI 2.7
20.6; one trial]. GRADE-Moderate quality evidence. CONCLUSIONS: Percutaneous
needle acupuncture treatments should not be recommended for infantile colic on a
general basis. Systematic review registration: PROSPERO 2015:CRD42015023253 Key
points The role of acupuncture in the treatment of infantile colic is
controversial. Available trials are small and present conflicting results. There
were no clinically important differences between infants receiving acupuncture
and no acupuncture control in this IPD meta-analysis of randomised controlled
trials. The data indicate that acupuncture induces some treatment pain in many of
the children. The study results indicate that percutaneous needle acupuncture
should not be recommended for treatment of infantile colic on a general basis.
PMID- 29338490
TI - Treatment approaches for nasopharyngeal adenoid cystic carcinoma.
PMID- 29338489
TI - Multimodal physiotherapy treatment based on a biobehavioral approach for patients
with chronic cervico-craniofacial pain: a prospective case series.
AB - The purpose of this prospective case series was to observe and describe changes
in patients with chronic cervico-craniofacial pain of muscular origin treated
with multimodal physiotherapy based on a biobehavioral approach. Nine patients
diagnosed with chronic myofascial temporomandibular disorder and neck pain were
treated with 6 sessions over the course of 2 weeks including: (1) orthopedic
manual physiotherapy (joint mobilizations, neurodynamic mobilization, and dynamic
soft tissue mobilizations); (2) therapeutic exercises (motor control and muscular
endurance exercises); and (3) patient education. The outcome measures of
craniofacial (CF-PDI) and neck disability (NDI), kinesiophobia (TSK-11) and
catastrophizing (PCS), and range of cervical and mandibular motion (ROM) and
posture were collected at baseline, and at 2 and 14 weeks post-baseline. Compared
to baseline, statistically significant (p < 0.01) and clinically meaningful
improvements that surpassed the minimal detectable change were observed at 14
weeks in CF-PDI (mean change, 8.11 points; 95% confidence interval (CI): 2.55 to
13.69; d = 1.38), in NDI (mean change, 5 cm; 95% CI: 1.74-8.25; d = 0.98), and in
the TSK-11 (mean change, 6.55 cm; 95% CI: 2.79-10.32; d = 1.44). Clinically
meaningful improvements in self-reported disability, psychological factors, ROM,
and craniocervical posture were observed following a multimodal physiotherapy
treatment based on a biobehavioral approach.
PMID- 29338492
TI - Genetic variation of GRIA3 gene is associated with vulnerability to
methamphetamine dependence and its associated psychosis.
AB - Methamphetamine (METH) is an addictive psychostimulant drug commonly leading to
schizophrenia-like psychotic symptoms. Disturbances in glutamatergic
neurotransmission have been proposed as neurobiological mechanisms and the alpha
amino-3 hydroxy-5 methyl-4 isoxazole propionic acid (AMPA) glutamate receptor has
been implicated in these processes. Moreover, genetic variants in GRIAs, genes
encoding AMPA receptor subunits, have been observed in association with both drug
dependence and psychosis. We hypothesized that variation of GRIA genes may be
associated with METH dependence and METH-induced psychosis. Genotyping of GRIA1
rs1428920, GRIA2 rs3813296, GRIA3 rs3761554, rs502434 and rs989638 was performed
in 102 male Thai controls and 100 METH-dependent subjects (53 with METH-dependent
psychosis). We observed no evidence of association with METH dependence and METH
dependent psychosis in the GRIA1 and GRIA2 polymorphisms, nor with single
polymorphisms rs3761554 and rs989638 in GRIA3. An association of GRIA3 rs502434
was identified with both METH dependence and METH-dependent psychosis, although
this did not withstand correction for multiple testing. Combining the analysis of
this site with the previously-demonstrated association with BDNF rs6265 resulted
in a highly significant effect. These preliminary findings indicate that genetic
variability in GRIA3 may interact with a functional BDNF polymorphism to provide
a strong risk factor for the development of METH dependence in the Thai
population.
PMID- 29338491
TI - The effect of ketamine on the consolidation and extinction of contextual fear
memory.
AB - Ketamine, principally an antagonist of N-methyl-?-aspartate receptors, induces
schizophrenia-like symptoms in adult humans, warranting its use in the
investigation of psychosis-related phenotypes in animal models. Genomic studies
further implicate N-methyl-?-aspartate receptor-mediated processes in
schizophrenia pathology, together with more broadly-defined synaptic plasticity
and associative learning processes. Strong pathophysiological links have been
demonstrated between fear learning and psychiatric disorders such as
schizophrenia. To further investigate the impact of ketamine on associative fear
learning, we studied the effects of pre- and post-training ketamine on the
consolidation and extinction of contextual fear memory in rats. Administration of
25 mg/kg ketamine prior to fear conditioning did not affect consolidation when
potentially confounding effects of state dependency were controlled for. Pre
training ketamine (25 mg/kg) impaired the extinction of the conditioned fear
response, which was mirrored with the use of a lower dose (8 mg/kg). Post
training ketamine (25 mg/kg) had no effect on the consolidation or extinction of
conditioned fear. These observations implicate processes relating to the
extinction of contextual fear memory in the manifestation of ketamine-induced
phenotypes, and are consistent with existing hypotheses surrounding abnormal
associative learning in schizophrenia.
PMID- 29338493
TI - Challenges of peroral endoscopic myotomy in the treatment of distal esophageal
spasm.
AB - OBJECTIVE: Distal esophageal spasm (DES) is a rare motility disorder
characterized by premature and rapidly propagated contractions of the distal
esophagus. Treatment options are limited and often poorly effective. Peroral
endoscopic myotomy (POEM) seems an effective and attractive new treatment option
for DES. In this case report we describe some of the difficulties that could
arise. MATERIALS AND METHODS: A 84-year old man with therapy-refractory DES and
complaints of severe dysphagia and chest pain underwent a POEM procedure under
general anesthesia. A longer myotomy was performed to cleave the circular muscle
layer from start till end of the spastic contractions. RESULTS: The length of the
myotomy was 16 cm. Hyperactive spastic contractions during the procedure
complicated the creation of the submucosal tunnel, extended the duration (134 vs.
60-90 min for achalasia), increased postoperative pain and prolonged hospital
admission. Intravenously nitroglycerin peroperative diminished spastic
contractions. Postoperative a remnant of spastic contractions was present,
proximal to the myotomy, causing persistent symptoms. CONCLUSION: Performing POEM
for DES is challenging due to reactive hyperactive spastic contractions during
the procedure causing technical difficulties and an extended procedure. A long
myotomy, several centimeters above the proximal border of the spastic region, is
essential to prevent remnants of spasticity.
PMID- 29338494
TI - Neural correlates of response inhibition in patients with bipolar disorder during
acute versus remitted phase.
AB - OBJECTIVES: Elevated behavioural impulsivity has been shown to be a core feature
of bipolar disorder. However, no study has so far investigated impulsivity
related brain activation in patients with BD during acute versus remitted phase.
To address the question whether elevated behavioural impulsivity and its
differential neural pathways is a state or trait marker of BD, we employed a
combined stop signal-go/no-go task in 30 controls, and 37 depressed and 15
remitted patients who were retested. METHODS: Frontal brain activation was
recorded using near-infrared spectroscopy. RESULTS: Behaviourally, we found
increased impulsivity as indexed by higher stop signal reaction time for patients
in their depressed phase while remitted patients did not differ from controls in
any measure. In contrast, brain activation measurements revealed an opposite
pattern: compared to controls, depressed patients did not show significant
differences, while the remitted group displayed significantly decreased
activation in bilateral prefrontal cortex during successful inhibition. Analysis
of the remaining conditions (go, no-go, unsuccessful inhibition) did not reveal
significant differences. CONCLUSIONS: Therefore, behavioural impulsivity and
prefrontal hypoactivation do not seem to be a trait marker of BD. As only
successful inhibition differentiated between groups, a specific dysfunction of
this inhibitory process and its neural pathway may be postulated in BD.
PMID- 29338495
TI - Clinical challenges in de novo pediatric acute myeloid leukemia.
AB - INTRODUCTION: Although the prognosis of pediatric acute myeloid leukemia (pAML)
has improved, with current survival rates up to 75%, relapse rates remain high.
Areas covered: The low number of patients, the heterogeneous genomic landscape of
AML, novel diagnostic techniques, divergent available treatment protocols, and
dose-limiting toxicity of conventional agents all contribute to the complexity of
AML treatment. This review gives an overview of the current clinical challenges
with respect to diagnostics, treatment, and supportive care in pAML. Expert
commentary: Due to intensified treatment regimens and improved supportive care
measures, the outcome for pAML patients has improved substantially over the past
years. However, most treatment protocols still rely on conventional
chemotherapeutic agents with significant toxicity. Although targeted therapies
promise to reduce the need for high doses of conventional agents with a
subsequent decrease in toxicity, the effectiveness of these strategies remains
unsatisfactory today. International collaborations are needed in order to address
the ongoing therapeutic challenges of reducing toxicity while increasing
effectivity. Consensus on risk-group classification, a common chemotherapy
backbone and evidence-based supportive care guidelines are necessary in this
context, at the same time enabling intergroup studies on new agents in subgroups.
PMID- 29338496
TI - Repeated lipopolysaccharide exposure modifies immune and sickness behaviour
response in an animal model of chronic inflammation.
AB - Repeated lipopolysaccharide exposure is often used in longitudinal preclinical
models of depression. However, the potential phenotypic differences from acute
depression-mimicking effects are rarely described. This study compared chronic
lipopolysaccharide administration of doses previously used in depression research
to a new mode of escalating dose injections. Adult male BALB/c mice ( n=8/group)
were injected intraperitoneally with either a single 0.83 mg/kg dose, a repeated
0.1 mg/kg lipopolysaccharide dose or a dose which escalated weekly from 0.33 to
0.83 mg/kg lipopolysaccharide for six weeks. The escalating lipopolysaccharide
group demonstrated most features of sickness behaviour such as weight loss and
reduction in food intake every week, whilst this effect was not sustained in
other groups. Moreover, only in the escalating lipopolysaccharide group did most
peripheral plasma cytokines levels, measured using Luminex multiplex technology,
such as interleukin-6, tumour necrosis factor alpha and interleukin-2 remain over
three-fold elevated on the sixth week. In addition, exposure to escalating doses
led to a reduction of neuroblast maturation in the dentate gyrus relevant for
depression neurobiology. Therefore, this mode of injections might be useful in
the studies attempting to replicate neurobiological aspects of the chronic
inflammatory state observed in mood disorders.
PMID- 29338497
TI - A prospective observational study comparing cardiac function of small for
gestational age with appropriate for gestational age babies using serial
echocardiographic studies.
AB - BACKGROUND: Approximately 30% of babies born in India are low birth weight (LBW)
and about 70% of LBW babies are small for gestational age (SGA). Though there are
several trials that have evaluated cardiac function of intrauterine growth
restricted (IUGR) babies in utero, there is limited data about postnatal cardiac
function in SGA babies during early neonatal period. This study was conducted to
evaluate the cardiac functions of SGA babies by serial echocardiographic
measurements and compare this with appropriate for gestational age (AGA) babies
during the early postnatal period. MATERIAL AND METHODS: Seventy babies were
enrolled in this prospective observational study with 35 each in the SGA and AGA
groups. Echocardiography was performed for all babies on days 1, 2, and 3 of
life. Myocardial performance index (MPI) was used as the primary measure to
compare cardiac function. MPI was calculated for both ventricles using pulse wave
Doppler and tissue Doppler. RESULTS: MPI of the left ventricle was significantly
higher in the SGA group as compared to AGA babies during all the three
measurement periods with SGA babies having significantly higher MPI of right
ventricle on day 1 and day 2 but not on day 3. Left ventricular internal diameter
index during diastole and systole (LVIDD index and LVIDS index), left atrium:
aortic root ratio (LA:AO ratio) were significantly increased in SGA babies on all
the occasions. Fractional shortening, ejection fraction, and area shortening were
similar in two groups. CONCLUSIONS: Myocardial performance index of left and
right ventricle, which evaluates both systolic and diastolic function of
ventricles, was significantly increased in SGA babies in comparison to AGA babies
during the first 3 days of life except MPI of the right ventricle on day 3. Thus,
SGA babies have compromised cardiac function through all phases of the cardiac
cycle with the performance improving spontaneously over time.
PMID- 29338498
TI - From clinical remission to residual disease activity in spondyloarthritis and its
potential treatment implications.
AB - INTRODUCTION: Remission or low disease activity should be the target of therapy
in spondyloarthritis (SpA). Due to the complexity of the disease, several
composite indices that assess all disease domains were proposed to define a
status of low disease activity/remission in both axial and peripheral SpA. With
the introduction, in the past years, of effective biologic and targeted synthetic
treatments aimed at inhibiting key cytokines and intracellular pathways, the goal
of clinical remission has become an achievable target in these conditions.
However, residual disease activity may occur in some domains and the management
of patients that achieve the target of remission is still an unmet need. Areas
covered: This manuscript aimed to review the current evidence on clinical
remission and residual disease activity in SpA (both axial SpA and psoriatic
arthritis), and its potential treatment implications. Expert commentary: Progress
in our understanding of the pathogenesis of SpA will lead to a rapid increase in
the number of available treatments, with the possibility for patients to achieve
a status of remission. However, the topic of residual disease activity should be
taken into consideration.
PMID- 29338499
TI - A milestone reached?
PMID- 29338501
TI - Does the evidence support the implementation of lung cancer screening with low
dose computed tomography?
PMID- 29338502
TI - The Health Information Manager as Consultant.
PMID- 29338503
TI - The Health Information Manager in a WA Division of General Practice: A
Multiskilled Occupation.
PMID- 29338504
TI - The Health Information Manager as Project Manager.
PMID- 29338505
TI - Taking on a New Role: The Health Information Manager in the Queensland Ambulance
Service.
PMID- 29338506
TI - The Health Information Manager in Correctional Health.
PMID- 29338507
TI - From Private to General Practice.
PMID- 29338508
TI - The Health Information Manager in a Division of General Practice: A Western
Australian Experience.
PMID- 29338509
TI - A Health Information Manager's Experience in Palliative Care.
PMID- 29338510
TI - The Health Information Manager in Epidemiological Research: From Coder to Program
Manager.
PMID- 29338511
TI - Health Authority Data Management and Analysis.
PMID- 29338512
TI - HIM in Special Health Services.
PMID- 29338513
TI - Health Authority Data Collection.
PMID- 29338514
TI - Portsea Safe Haven - From DRGs to Refugees.
PMID- 29338515
TI - Feel like a Change? Read about Health Information Managers in Non-Traditional
Jobs.
PMID- 29338516
TI - Electronic Health Record System Risk Assessment: A Case Study from the MINET.
AB - This article discusses the risk assessment of a health information system. A case
study was conducted at the South Western Sydney Area Health Service to examine
the potential risks of the Maternal and Infant Network (MINET) health information
system using Failure Mode Effect Analysis (FMEA). FMEA was conducted by utilising
safety attributes identified by the authors. Potential failure modes of the
system were identified by the study. From this study, it can be concluded that
FMEA is an appropriate risk-assessment method for MINET.
PMID- 29338517
TI - Register-Recall Systems: Tools for Chronic Disease Management in General
Practice.
AB - The Divisions Diabetes and Cardiovascular Disease Quality Improvement Project
(DDCQIP) is a national project that aims to promote quality improvement
initiatives among Divisions of General Practice. DDCQIP has investigated the
growth of Division-based diabetes and cardiovascular disease register-recall
systems and the role they play in promoting evidence-based structured care within
general practice. In the period 2000-2002, an increase in the number of GPs using
register-recall systems and the rise in the number of active registered patients
have made it possible to monitor quality of care and health outcome indicators,
and contributed to the growth of a Division-based population health program.
PMID- 29338518
TI - An 'Arresting' Kind of Job for a Health Information Manager: Working in SAPOL.
PMID- 29338519
TI - A 'Secure' Kind of Job: The Health Information Manager in the NSW Corrections
Health Service.
PMID- 29338520
TI - The Role of the Health Information Manager in Forensic Mental Health.
PMID- 29338521
TI - Best Practice for the Design of Forms.
AB - A major objective following the 1997 amalgamation of three health services in
Ballarat, Victoria, was the integration of the three discrete medical records
into one system. This article describes the multidisciplinary collaboration,
under the leadership of health information managers, that played a critical role
in this project. Standards and best-practice evidence were used to inform new
guidelines for forms design and development. This was complemented by another
project to develop best-practice guidelines for producing consumer information
with a focus on readability. Issues related to designing electronic forms were
considered, but further work is required so that best-practice principles are
available to guide designers. A sub-committee has been established with delegated
authority to approve all forms. Initial evaluations have demonstrated marked
improvements in the quality of new and revised forms.
PMID- 29338522
TI - Health Informatics and Health Information Management in Maternal and Child Health
Services.
AB - In November 1997, the South Western Sydney Area Health Service launched the
Mother and Infant Network (MINET). The key objective of MINET is to develop an
integrated clinical data network which has the capacity to inform and support a
continuum of care for the population of all mothers, infants and children. The
MINET data network integrates in-patient services, ambulatory services, and
community-based services. The focus of this article is the development and
implementation of MINET with reference to the crucial role of data linkage and
health informatics in health outcomes/health services research.
PMID- 29338523
TI - Standards for Health Information and Related Health Information Technology.
PMID- 29338524
TI - Visceral adiposity index is associated with premature ejaculation inversely: a
cross-sectional study.
AB - OBJECTIVE: Visceral adiposity index (VAI) is a novel indicator for the assessment
of visceral obesity. In this study, we aimed to evaluate the relationship between
VAI and premature ejaculation (PE). MATERIALS AND METHOD: A total of 300 men were
included in the study. Hundred and fifty men with PE and 150 men without PE
(control). All men were evaluated for PE by premature ejaculation diagnostic tool
(PEDT). VAI levels were calculated using body mass index (BMI), high density
lipoprotein and triglyceride (TG) levels. RESULTS: Mean age of the study groups
was 34.3 +/- 5.2 (30-60) years and the mean age of the controls were 35.9 +/- 5.3
(30-60) years. The men with PE had lower BMI, TG levels, waist circumference (WC)
and higher high-density lipoprotein-cholesterol (HDL-C) levels. Mean VAI level
was 4.13 +/- 0.7 in study group and 5.72 +/- 1.6 in control group, respectively.
VAI levels were statistically higher in men without PE (p < .001). DISCUSSION:
Our cross-sectional study demonstrated a negative correlation between VAI and PE.
VAI is superior index for the evaluation and calculation the relationship between
obesity and PE.
PMID- 29338527
TI - Privacy - It's Your Issue.
PMID- 29338525
TI - Pyocyanin induces systemic oxidative stress, inflammation and behavioral changes
in vivo.
AB - Pyocyanin (PCN) is a virulence factor secreted by Pseudomonas aeruginosa (P.
aeruginosa) that has been shown to have numerous toxic effects in both in vitro
and in vivo studies. Such toxicities include pro-inflammatory and pro-oxidant
mediated responses. It is hypothesized that PCN can cross biological membranes
and reach the systemic circulation, but no previous studies have investigated
this. The aim of this study was, therefore, to quantify PCN in plasma and assess
if systemic responses were occurring after localized intranasal administration in
C57BL/6 J mice. This was achieved through the plasma quantification of PCN and
assessment of changes to behavior using two commonly used tests, the forced
swimming test and the open field test. Furthermore, evidence of systemic
oxidative stress and inflammation was measured using malondialdehyde (MDA) and
TNF-alpha post PCN exposure. PCN was found to cross into systemic circulation but
in a variable manner. Furthermore, significant increases in plasma TNF-alpha and
MDA (both p < 0.001) were observed along with changes in behavior indicative of
systemic inflammatory responses.
PMID- 29338528
TI - The Privacy Imperative for a Successful Health Connect.
PMID- 29338526
TI - Associations of Abdominal Subcutaneous and Visceral Fat with Insulin Resistance
and Secretion Differ Between Men and Women: The Netherlands Epidemiology of
Obesity Study.
AB - BACKGROUND: Abdominal obesity is a well-established risk factor for the
development of type 2 diabetes. However, sex differences may exist. We aimed to
investigate the associations of abdominal subcutaneous adipose tissue (SAT) and
visceral adipose tissue (VAT) with insulin resistance and insulin secretion in
men and women. METHODS: In this cross-sectional analysis of the Netherlands
Epidemiology of Obesity study, fasting and postprandial concentrations of glucose
and insulin were measured and abdominal fat depots were assessed using magnetic
resonance imaging in 2253 participants (53% women). With linear regression
analysis, we examined associations of abdominal SAT and VAT with measures of
insulin resistance and insulin secretion in men and women, while adjusting for
age, ethnicity, education, smoking habits, alcohol consumption, menopausal state
and hormone use in women, and models with VAT additionally for total body fat.
RESULTS: Participants had a mean [standard deviation (SD)] age of 56 (6) years,
body mass index: 25.9 (3.9) kg/m2, VAT: 89 (55) cm2, and SAT: 235 (95) cm2. In
the multivariate models in men, per SD of VAT the homeostatic model assessment of
insulin resistance (HOMA-IR) was 20% (95% CI: 14-26) higher, and per SD SAT 21%
(15-27) higher. In women, per SD of VAT the HOMA-IR was 40% (29-52) higher, and
per SD SAT 12% (6-19) higher. Associations with measures of insulin secretion
were weaker than with insulin resistance. CONCLUSIONS: In men, abdominal SAT and
VAT were associated with insulin resistance to a similar extent, whereas in women
particularly VAT was associated with insulin resistance and insulin secretion.
Future studies need to unravel the mechanisms underlying the metabolic effects of
visceral fat in women. Simple and less expensive measures that can distinct
abdominal subcutaneous and visceral fat are needed for an improved metabolic risk
stratification.
PMID- 29338529
TI - Health Connect: Making Consent and Privacy a Priority.
PMID- 29338530
TI - Clinical Coding Audits: An Annotated Bibliography.
PMID- 29338531
TI - The Implications of Data Privacy Legislation for the Development of Hospital
Information Systems.
AB - This research provides an analysis of the implementation of medical data privacy
law in Australia, with emphasis on the Victorian Health Records Act 2001 (HRA).
We examine the ability of health organisations to respond to the requirements of
this legislation, and similar health privacy legislation elsewhere, and
illustrate that this ability is affected by the quality of their patient data and
the structure and security of their databases. This article suggests that
compliance with the legislative provisions creates implications for information
systems development and design, which large public and private hospitals have so
far failed to consider or act upon.
PMID- 29338532
TI - Health Privacy: The Draft Australian National Health Privacy Code and the Shared
Longitudinal Electronic Health Record.
AB - An explicit distinction between shared electronic health records and those at the
point of care is required when referring to electronic health records. The former
raises particular privacy issues discussed in this paper in relation to Health
Connect and the Draft Australian National Health Privacy Code. In addition to a
number of revisions to the code, the analysis recommends that related legislation
such as archival and freedom of information law should be reconciled as much as
possible within the code, so that a long-term view of the uses, retention and
preservation of the longitudinal electronic health record is balanced with
privacy, confidentiality and public interest.
PMID- 29338533
TI - Enhanced solubility, oral bioavailability and anti-osteoporotic effects of
raloxifene HCl in ovariectomized rats by Igepal CO-890 nanomicelles.
AB - The purpose of the present study was to enhance the bioavailability and anti
osteoporotic effects of raloxifene HCl (RH) by increasing its solubility and
inhibition of the p-glycoprotein pump using surfactant micelles of Igepal CO-890.
The micelles were prepared by the direct method and their critical micellar
concentration, drug dissolution rate, saturated solubility, drug loading and
surface morphology were defined. The cytotoxicity of Igepal CO-890 and its
ability to inhibit the p-glycoprotein pump were studied on Caco-2 cells. The
pharmacokinetic parameters were analyzed by oral administration of a single dose
of 15 mg/kg in Wistar rats. Anti-osteoporotic effects were studied by measuring
the calcium, phosphorous, and uterus weight of rats after one month of oral
administration of 6 mg/kg/day of RH in ovariectomized rats. Igepal CO-890
micelles enhanced the RH solubility by about two-fold. The FT-IR and DSC studies
indicated no interaction between the drug and the surfactant. XRD spectrum showed
an amorphous state of RH in the micelles. The p-glycoprotein pump was inhibited
by Igepal CO-890 in Caco-2 cells comparable to verapamil. Micelles increased the
uterine weight and decreased the serum calcium and phosphorus significantly
compared to the untreated drug. Oral bioavailability of RH increased about four
fold by nanomicelles.
PMID- 29338534
TI - Health Information Management Journal Reviewers 2017.
PMID- 29338535
TI - Different lymph node staging systems for patients with adenocarcinoma of
esophagogastric junction.
AB - OBJECTIVE: In addition to the traditional TNM N staging system, lymph node ratio
(LNR) and log odds of metastatic lymph nodes (LODDS) staging methods were
developed in cancers. This study aimed to examine their relative prognostic
performance in patients with adenocarcinoma of the esophagogastric junction
(AEG). PATIENTS AND METHODS: Patients who underwent surgical resection for AEG
were identified from the Surveillance, Epidemiology, and End Results (SEER)
Program and the First Affiliated Hospital of Xi'an Jiaotong University as the
training and validation sets, respectively. The Akaike's Information Criterion
(AIC), Harrell's C statistic, and ROC curves were utilized for comparison.
RESULTS: A total of 735 patients were involved in the training set. LODDS and LNR
staging systems had better prognostic performance than the TNM N staging systems
(when considered as a categorical variable: C index = 0.728 and 0.712 vs 0.671;
AIC: 6247.537 and 6265.996 vs 6320.045; AUC: 0.762 and 0.719 vs 0.692. For the
continuous model: C index = 0.675 and 0.686 vs 0.658; AIC = 6243.740 and 6261.027
vs 6355.077; AUC = 0.778 and 0.733 vs 0.693). In the validation set of 183
patients, the TNM N staging scheme outperformed the LODDS and LNR staging systems
(C index = 0.788 vs 0.779 and 0.767; AIC = 1014.702 vs 1026.899 and 1025.288; AUC
= 0.806 vs 0.787 and 0.791) when considered a categorical variable. However, when
considered a continuous variable, the LODDS and LNR staging systems were better
than the TNM N staging system (C index = 0.724 and 0.733 vs 0.747; AIC = 1018.075
and 1025.803 vs 1026.085; AUC = 0.811 and 0.810 vs 0.806). CONCLUSIONS: The LNR
and LODDS staging schemes could be considered new options for prognostic
prediction of AEG with respect to lymph node status, especially when considered
as continuous variables.
PMID- 29338536
TI - P2Y12 receptor inhibitors: an evolution in drug design to prevent arterial
thrombosis.
AB - INTRODUCTION: P2Y12 inhibitors are a critical component of dual antiplatelet
therapy (DAPT), which is the superior strategy to prevent arterialthrombosis in
patients with acute coronary syndromes (ACS) and undergoing stent implantation..
Areas covered: Basic science articles, clinical studies, and reviews from 1992
2017 were searched using Pubmed library to collet impactful literature. After an
introduction to the purinergic receptor biology, this review summarizes current
knowledge on P2Y12 receptor inhibitors. Furthermore, we describe the subsequent
improvements of next-generation P2Y12 receptor inhibitors facing the ambivalent
problem of bleeding events versus prevention of arterial thrombosis in a variety
of clinical settings. Therefore, we summarize data from relevant preclinical and
clinical trials of currently approved P2Y12 receptor inhibitors (clopidogrel,
prasugrel, ticagrelor, cangrelor) and provide strategies of drug switching and
management of bleeding events. Expert opinion: An enormous amount of
pharmacologic and clinical data is available for the application of P2Y12
receptor inhibitors. Today prasugrel, ticagrelor and clopidogrel are the standard
of care drugs during dual antiplatelet therapy for ACS patients, but have
considerable rates of bleeding. Recent and future clinical trials will provide
evidence for subsequent escalation and de-escalation strategies of P2Y12 receptor
inhibition. These data may pave the way for an evidence-based, individualized
P2Y12 receptor inhibitor therapy.
PMID- 29338537
TI - Antidepressant prescriptions and mental health nurses: an observational study in
Dutch general practice from 2011 to 2015.
AB - PURPOSE: The purpose of this study was to investigate developments in
antidepressant prescriptions by Dutch general practitioners, alongside the
national introduction of mental health nurses. Antidepressant prescriptions are
very common in general practice, but are often not in line with recommendations.
The recent introduction of mental health nurses may have decreased antidepressant
prescriptions, as general practitioners (GPs) have greater potential to offer
psychological treatment as a first choice option instead of medication. MATERIAL
AND METHODS: Anonymised data from the medical records of general practices
participating in the NIVEL Primary Care Database in 2011-2015 were analysed in an
observational study. We used multilevel logistic regression analyses to determine
whether total antidepressant prescriptions and antidepressants prescribed within
one week of diagnosing anxiety or depression decreased in the period 2011-2015.
We analysed whether changes in antidepressant prescriptions were associated with
the employment or consultation of mental health nurses. RESULTS: Antidepressants
were prescribed in 30.3% of all anxiety or depression episodes; about half were
prescribed within the first week. Antidepressants prescriptions for anxiety or
depression increased slightly in the period 2011-2015. The employment of mental
health nurses was not associated with a decreased number of prescriptions of
antidepressants. Patients who had at least one mental health nurse consultation
had fewer immediate prescriptions of antidepressants, but not fewer
antidepressants in general. CONCLUSIONS: Antidepressant prescriptions are still
common in general practice. So far, the introduction of mental health nurses has
not decreased antidepressant prescriptions, but it may have a postponing effect.
PMID- 29338538
TI - Increased nature relatedness and decreased authoritarian political views after
psilocybin for treatment-resistant depression.
AB - RATIONALE: Previous research suggests that classical psychedelic compounds can
induce lasting changes in personality traits, attitudes and beliefs in both
healthy subjects and patient populations. AIM: Here we sought to investigate the
effects of psilocybin on nature relatedness and libertarian-authoritarian
political perspective in patients with treatment-resistant depression (TRD).
METHODS: This open-label pilot study with a mixed-model design studied the
effects of psilocybin on measures of nature relatedness and libertarian
authoritarian political perspective in patients with moderate to severe TRD (
n=7) versus age-matched non-treated healthy control subjects ( n=7). Psilocybin
was administered in two oral dosing sessions (10 mg and 25 mg) 1 week apart. Main
outcome measures were collected 1 week and 7-12 months after the second dosing
session. Nature relatedness and libertarian-authoritarian political perspective
were assessed using the Nature Relatedness Scale (NR-6) and Political Perspective
Questionnaire (PPQ-5), respectively. RESULTS: Nature relatedness significantly
increased ( t(6)=-4.242, p=0.003) and authoritarianism significantly decreased (
t(6)=2.120, p=0.039) for the patients 1 week after the dosing sessions. At 7-12
months post-dosing, nature relatedness remained significantly increased ( t(5)=
2.707, p=0.021) and authoritarianism remained decreased at trend level ( t(5)=
1.811, p=0.065). No differences were found on either measure for the non-treated
healthy control subjects. CONCLUSIONS: This pilot study suggests that psilocybin
with psychological support might produce lasting changes in attitudes and
beliefs. Although it would be premature to infer causality from this small study,
the possibility of drug-induced changes in belief systems seems sufficiently
intriguing and timely to deserve further investigation.
PMID- 29338539
TI - Primary Care Provider Experience with Breast Density Legislation in
Massachusetts.
AB - BACKGROUND: Dense breasts on mammography independently increases breast cancer
risk and decreases mammography sensitivity. Thirty-two states have adopted
notification laws to raise awareness among women with dense breasts about
supplemental screening. Little is known about these policies' impact on clinical
practice among primary care providers (PCPs). MATERIALS AND METHODS: This study
explores PCP attitudes, knowledge, and the impact of the Massachusetts dense
breast notification legislation on clinical practice after its enactment in 2015.
An anonymous, online survey at two urban safety-net hospitals was administered in
2015-2016. Practicing MDs and nurse practitioners in primary care were invited to
participate. RESULTS: All 145 PCPs in general internal medicine at the two sites
were e-mailed a survey link and 80 (55%) were completed. While 64 of 80 PCPs
surveyed (80%) had some familiarity with the legislation, none identified the 8
required components of notifications contained in the Massachusetts legislation.
Forty-nine percent (39/80) did not feel prepared to respond to patient questions
about dense breasts. Forty-one percent (33/80) correctly identified that no
current guidelines recommend the use of supplemental screening tests solely based
on breast density and 85% (68/80) indicated interest in further training. Female
and less experienced providers were more likely to be in favor of the legislation
(49% vs. 11% by gender; 76% <5 years vs. 9%> 20 years). Women practitioners (55%)
who were more likely than men (17%, p = 0.01) to agree with the policy changed
their discussions of mammography results with patients. CONCLUSIONS: PCPs feel
underprepared to counsel women about breast density identified on mammography and
its implications.
PMID- 29338540
TI - Efficacy and safety of frontline rituximab, cyclophosphamide, doxorubicin and
prednisone plus bortezomib (VR-CAP) or vincristine (R-CHOP) in a subset of newly
diagnosed mantle cell lymphoma patients medically eligible for transplantation in
the randomized, phase 3 LYM-3002 study.
AB - This post-hoc subanalysis of the LYM-3002 phase 3 study assessed the efficacy and
safety of substituting vincristine in rituximab, cyclophosphamide, doxorubicin
and prednisone (R-CHOP; n = 42) for bortezomib (VR-CAP; n = 38) in a subgroup of
80 mantle cell lymphoma (MCL) patients aged <60 years who did not receive stem
cell transplantation (SCT) despite medical eligibility. Complete response
(CR)/unconfirmed CR (CRu) rates were 67 vs. 39% (odds ratio 3.69 [95%
CI(confidence interval): 1.31, 10.41]; p = .012). After 40 months median follow
up, median progression-free survival by independent radiology committee with VR
CAP vs. R-CHOP was 32.6 vs. 12.0 months (hazard ratio (HR) 0.59 [95% CI: 0.31,
1.13]; p = .108); median overall survival was not reached vs. 47.3 months (HR
0.81 [95% CI: 0.33, 1.96]; p = .634). Adverse events included neutropenia
(92/76%), thrombocytopenia (70/10%) and leukopenia (65/50%). VR-CAP represents a
potential alternative to R-CHOP in combined and/or alternating regimens for
younger, SCT-eligible MCL patients.
PMID- 29338541
TI - Diagnostic Accuracy of Clinical Measures Considering Segmental Tissue Composition
and Volume Changes of Breast Cancer-Related Lymphedema.
AB - BACKGROUND: If we use only volumetry for measuring lymphedema, we could
underdiagnose lymphedema with characteristics of biomechanical changes without
definite volume change, especially in the medial forearm. METHODS AND RESULTS: In
total, 158 breast cancer patients participated in this study. Arm volume was
measured by water displacement volumetry, and segmental volumes were calculated
from circumferences by using the truncated cone method. Subcutaneous ultrasound
echogenicities were assessed on the medial side of the upper arm and forearm of
both arms and graded by subcutaneous echogenicity grade (SEG) and revised SEG
(rSEG). The standards for diagnosing secondary lymphedema were according to the
volume change and clinical stage. Sensitivity, specificity, receiver-operating
characteristic (ROC) curve, and area under the curve (AUC) were used. Analysis of
ROC curves yielded AUCs of 0.875-0.933 (p < 0.001). Volume differences in each
segment were significantly different among the grades by SEG. The highest AUC was
found for volume difference (AUC = 0.919, 95% confidence interval [CI] = 0.860
0.978) in the upper arm near the elbow; however, in the medial forearm, the
highest AUC was found for rSEG (AUC = 0.948, 95% CI = 0.923-0.965 in the proximal
forearm; AUC = 0.940, 95% CI = 0.923-0.965 in the distal forearm). CONCLUSIONS:
Our findings support the use of SEG by ultrasound in the assessment of
lymphedema, especially in the medial region of the forearm. Subcutaneous
ultrasound echogenicities may improve the accuracy of diagnosis of lymphedema in
the forearm.
PMID- 29338542
TI - The novel microtubule-associated CAP-glycine protein Cgp1 governs growth,
differentiation, and virulence of Cryptococcus neoformans.
AB - Microtubules are involved in mechanical support, cytoplasmic organization, and
several cellular processes by interacting with diverse microtubule-associated
proteins such as plus-end tracking proteins, motor proteins, and tubulin-folding
cofactors. A number of the cytoskeleton-associated proteins (CAPs) contain the
CAP-glycine-rich (CAP-Gly) domain, which is evolutionarily conserved and
generally considered to bind to alpha-tubulin to regulate the function of
microtubules. However, there has been a dearth of research on CAP-Gly proteins in
fungal pathogens, including Cryptococcus neoformans, which is a global cause of
fatal meningoencephalitis in immunocompromised patients. In this study, we
identified five CAP-Gly protein-encoding genes in C. neoformans. Among these,
Cgp1 encoded by CNAG_06352 has a unique domain structure containing CAP-Gly,
SPEC, and Spc7 domains that is not orthologous to CAPs in other eukaryotes.
Supporting the role of Cgp1 in microtubule-related function, we demonstrate that
deletion or overexpression of CGP1 alters cellular susceptibility to
thiabendazole, a microtubule destabilizer and that Cgp1 is co-localized with
cytoplasmic microtubules. Related to the cellular function of microtubules, Cgp1
governs the maintenance of membrane stability and genotoxic stress responses.
Deletion of CGP1 also reduces production of melanin pigment and attenuates the
virulence of C. neoformans. Furthermore, we demonstrate that Cgp1 uniquely
regulates the sexual differentiation of C. neoformans with distinct roles in the
early and late stage of mating. Domain analysis revealed that the CAP-Gly domain
plays a major role in all Cgp1 functions examined. In conclusion, this novel CAP
Gly protein, Cgp1, has pleotropic roles in regulating growth, stress responses,
differentiation, and virulence in C. neoformans.
PMID- 29338544
TI - A Direct Comparison between Norepinephrine and Phenylephrine for Augmenting
Spinal Cord Perfusion in a Porcine Model of Spinal Cord Injury.
AB - Current clinical guidelines recommend elevating the mean arterial blood pressure
(MAP) to increase spinal cord perfusion in patients with acute spinal cord injury
(SCI). This is typically achieved with vasopressors such as norepinephrine (NE)
and phenylephrine (PE). These drugs differ in their pharmacological properties
and potentially have different effects on spinal cord blood flow (SCBF),
oxygenation (PO2), and downstream metabolism after injury. Using a porcine model
of thoracic SCI, we evaluated how these vasopressors influenced intraparenchymal
SCBF, PO2, hydrostatic pressure, and metabolism within the spinal cord adjacent
to the injury site. Yorkshire pigs underwent a contusion/compression SCI at T10
and were randomized to receive either NE or PE for MAP elevation of 20 mm Hg, or
no MAP augmentation. Prior to injury, a combined SCBF/PO2 sensor, a pressure
sensor, and a microdialysis probe were inserted into the spinal cord adjacent to
T10 at two locations: a "proximal" site and a "distal" site, 2 mm and 22 mm from
the SCI, respectively. At the proximal site, NE and PE resulted in little
improvement in SCBF during cord compression. Following decompression, NE resulted
in increased SCBF and PO2, whereas decreased levels were observed for PE.
However, both NE and PE were associated with a gradual decrease in the lactate to
pyruvate (L/P) ratio after decompression. PE was associated with greater
hemorrhage through the injury site than that in control animals. Combined, our
results suggest that NE promotes better restoration of blood flow and oxygenation
than PE in the traumatically injured spinal cord, thus providing a physiological
rationale for selecting NE over PE in the hemodynamic management of acute SCI.
PMID- 29338543
TI - Lucidone suppresses dengue viral replication through the induction of heme
oxygenase-1.
AB - Dengue virus (DENV) infection causes life-threatening diseases such as dengue
hemorrhagic fever and dengue shock syndrome. Currently, there is no effective
therapeutic agent or vaccine against DENV infection; hence, there is an urgent
need to discover anti-DENV agents. The potential therapeutic efficacy of lucidone
was first evaluated in vivo using a DENV-infected Institute of Cancer Research
(ICR) suckling mouse model by monitoring body weight, clinical score, survival
rate, and viral titer. We found that lucidone effectively protected mice from
DENV infection by sustaining survival rate and reducing viral titers in DENV
infected ICR suckling mice. Then, the anti-DENV activity of lucidone was
confirmed by western blotting and quantitative-reverse-transcription-polymerase
chain reaction analysis, with an EC50 value of 25 +/- 3 MUM. Lucidone
significantly induced heme oxygenase-1 (HO-1) production against DENV replication
by inhibiting DENV NS2B/3 protease activity to induce the DENV-suppressed
antiviral interferon response. The inhibitory effect of lucidone on DENV
replication was attenuated by silencing of HO-1 gene expression or blocking HO-1
activity. In addition, lucidone-stimulated nuclear factor erythroid 2-related
factor 2 (Nrf2), which is involved in transactivation of HO-1 expression for its
anti-DENV activity. Taken together, the mechanistic investigations revealed that
lucidone exhibits significant anti-DENV activity in in vivo and in vitro by
inducing Nrf2-mediated HO-1 expression, leading to blockage of viral protease
activity to induce the anti-viral interferon (IFN) response. These results
suggest that lucidone is a promising candidate for drug development.
PMID- 29338545
TI - Identification of G2/M phase transition by sequential nuclear and cytoplasmic
changes and molecular markers in mice intestinal epithelial cells.
AB - Although the regulatory network of G2/M phase transition has been intensively
studied in mammalian cell lines, the identification of morphological and
molecular markers to identify G2/M phase transition in vivo remains elusive. In
this study, we found no obvious morphological changes between the S phase and G2
phase in mice intestinal epithelial cells. The G2 phase could be identified by
Brdu incorporation resistance, marginal and scattered foci of histone H3
phosphorylated at Ser10 (pHH3), and relatively intact Golgi ribbon. Prophase
starts with nuclear transformation in situ, which was identified by a series of
prophase markers including nuclear translocation of cyclinB1, fragmentation of
the Golgi complex, and a significant increase in pHH3. The nucleus started to
move upwards in the late prophase and finally rounded up at the apical surface.
Then, metaphase was initiated as the level of pHH3 peaked. During anaphase and
telophase, pHH3 sharply decreased, while Ki67 was obviously bound to chromosomes,
and PCNA was distributed throughout the whole cell. Based on the aforementioned
markers and Brdu pulse labeling, it was estimated to take about one hour for most
crypt cells to go through the G2 phase and about two hours to go through the G2-M
phase. It took much longer for crypt base columnar (CBC) stem cells to undergo G2
prophase than rapid transit amplifying cells. In summary, a series of
sequentially presenting markers could be used to indicate the progress of G2/M
events in intestinal epithelial cells and other epithelial systems in vivo.
PMID- 29338546
TI - Estimation of the volume under the receiver-operating characteristic surface
adjusting for non-ignorable verification bias.
AB - The receiver-operating characteristic surface is frequently used for presenting
the accuracy of a diagnostic test for three-category classification problems. One
common problem that can complicate the estimation of the volume under receiver
operating characteristic surface is that not all subjects receive the
verification of the true disease status. Estimation based only on data from
subjects with verified disease status may be biased, which is referred to as
verification bias. In this article, we propose new verification bias correction
methods to estimate the volume under receiver-operating characteristic surface
for a continuous diagnostic test. We assume the verification process is missing
not at random, which means the missingness might be related to unobserved
clinical characteristics. Three classes of estimators are proposed, namely,
inverse probability weighted, imputation-based, and doubly robust estimators. A
jackknife estimator of variance is derived for all the proposed volume under
receiver-operating characteristic surface estimators. The finite sample
properties of the new estimators are examined via simulation studies. We
illustrate our methods with data collected from Alzheimer's disease research.
PMID- 29338548
TI - Glycine transporter-1 inhibitors: a patent review (2011-2016).
AB - INTRODUCTION: Numerous research groups have developed GlyT-1 inhibitors in the
pursuit of providing a novel antipsychotic treatment for schizophrenia. Despite
multiple compounds advancing into clinical trials, a GlyT-1 inhibitor has yet to
emerge to treat patients. However, the approach remains heavily investigated as
it presents potential therapeutic utility for several other CNS and non-CNS
related indications. Areas covered: This review discusses various GlyT-1
inhibitor chemotypes identified and provides an overview of patent applications
filed and published during the period of 2011-2016. The review largely focuses on
composition of matter patent applications, although two recently disclosed method
of use patents are discussed. Clinical reports are also disseminated. Expert
opinion: Mounting clinical failures with schizophrenic patients have blunted
enthusiasm for GlyT-1 inhibition as an approach to treat the disease. However,
research in the area remains quite active, as therapeutic potential for several
additional indications has emerged. There are numerous and diverse GlyT-1
chemotypes now available that exhibit differentiating modes of binding and ligand
target binding kinetics, and this rich diversity of chemical matter may help
further elucidate the target's pharmacological role in various indications and
lead to the identification of a compound with optimal properties that may someday
become a drug.
PMID- 29338549
TI - Sedation in cardiac arrhythmias management.
AB - INTRODUCTION: Procedural sedation is of paramount importance for a plethora of
electrophysiological procedures. From electrical cardioversion to
electrophysiology studies, device implantations, and catheter ablations,
intraprocedural sedation and anesthesia have a pivotal role in allowing
procedural success while ensuring patient safety and avoiding discomfort. Areas
covered: The present review will discuss the current state-of-the-art in sedation
and anesthesia during electrical cardioversion, cardiac implantable electronic
device implantation, catheter ablation and electrophysiology studies. Specific
information will be provided for each procedure in order to reach the core of
this important clinical issue, and specific protocols will be compared. The main
pro-arrhythmic and anti-arrhythmic effects of the most commonly used sedatives
will also be discussed. Expert commentary: According to much recent evidence, the
cardiologist can be the only person responsible for sedation administration in
many settings, highlighting few safety issues associated with the absence of a
dedicated anesthesiologist thus a concomitant reduction in costs. However, many
concerns have been raised in allowing non-anesthesiologists to manage sedatives,
as adverse events, while rare, could have catastrophic consequences. The present
paper will highlight when a cardiologist-directed sedation is considered safe,
how it should be performed, and the pros and cons related to this strategy.
PMID- 29338547
TI - Neuroimaging meta-analysis of cannabis use studies reveals convergent functional
alterations in brain regions supporting cognitive control and reward processing.
AB - Lagging behind rapid changes to state laws, societal views, and medical practice
is the scientific investigation of cannabis's impact on the human brain. While
several brain imaging studies have contributed important insight into
neurobiological alterations linked with cannabis use, our understanding remains
limited. Here, we sought to delineate those brain regions that consistently
demonstrate functional alterations among cannabis users versus non-users across
neuroimaging studies using the activation likelihood estimation meta-analysis
framework. In ancillary analyses, we characterized task-related brain networks
that co-activate with cannabis-affected regions using data archived in a large
neuroimaging repository, and then determined which psychological processes may be
disrupted via functional decoding techniques. When considering convergent
alterations among users, decreased activation was observed in the anterior
cingulate cortex, which co-activated with frontal, parietal, and limbic areas and
was linked with cognitive control processes. Similarly, decreased activation was
observed in the dorsolateral prefrontal cortex, which co-activated with frontal
and occipital areas and linked with attention-related processes. Conversely,
increased activation among users was observed in the striatum, which co-activated
with frontal, parietal, and other limbic areas and linked with reward processing.
These meta-analytic outcomes indicate that cannabis use is linked with
differential, region-specific effects across the brain.
PMID- 29338550
TI - The role of tumor angiogenesis as a therapeutic target in colorectal cancer.
AB - INTRODUCTION: Angiogenesis is a complex process regulated by several pro- and
anti-angiogenic factors, thus the loss of its fine equilibrium plays a key role
in colorectal cancer (CRC) development and progression. Therapeutic agents
targeting VEGF/VEGFR signaling, the main regulator of this process, proved to be
effective across different treatment lines in metastatic CRC (mCRC) and
contributed greatly to improve patients' survival in recent years. Areas covered:
This review aimed to summarize the actual body of knowledge available on the VEGF
pathway in CRC, including currently available anti-angiogenic drugs and treatment
challenges, mechanisms of resistance, promising predictive biomarkers and future
perspectives. Expert commentary: Angiogenesis inhibition in subsequent lines of
treatment is a valid strategy in the continuum of care of mCRC patients. In this
scenario, the availability of multiple agents warrants to tailor therapy to an
individualized approach. However, the validation of predictive biomarkers to aid
therapeutic decisions remains an issue. Intrinsic and adaptive resistance to anti
angiogenic agents comprises distinct and intertwined processes, eventually
leading to treatment failure and disease progression. The expanding knowledge on
the mechanisms underlying the angiogenesis pathway, different potential treatment
targets and mechanisms of tumor resistance, may lead to promising new
perspectives in this field.
PMID- 29338551
TI - The regulatory roles of B cell subsets in transplantation.
AB - INTRODUCTION: B cells mediate allograft rejection through antigen presentation,
and production of cytokines and antibodies. More and more immunosuppressive
agents specifically targeting B cells and plasma cells have been applied in
clinical transplantation. However, recent studies have indicated the regulatory
roles of B cells. Therefore, it is vital to clarify the different effects of B
cell subsets in organ transplantation so that we can completely understand the
diverse functions of B cells in transplantation. Areas covered: This review
focuses on the regulatory roles of B cells in transplantation. B cell subsets
with immune modulation and factors mediating immunosuppressive functions of
regulatory B (Breg) cells were analyzed. Therapies targeting B cells and the
application of B cells for transplant tolerance induction were discussed. Expert
commentary: Besides involving rejection, B cells could also play regulatory roles
in transplantation. Breg cells and the related markers may be used to predict the
immune tolerant state in transplant recipients. New therapeutic strategies
targeting B cells should be explored to promote tolerance induction with less
impact on the host's protective immunity in organ transplanted patients.
PMID- 29338552
TI - The Adverse Drug Reactions Reporting Project.
PMID- 29338553
TI - Comprehensive Clinicopathologic and Updated Immunohistochemical Characterization
of Primary Ovarian Mucinous Carcinoma.
AB - The distinction of primary mucinous ovarian carcinoma (PMOC) from other primaries
or secondaries is essential for selecting therapeutic options and
prognostication. We aimed to characterize the immunohistochemical profile of 36
PMOCs using an extended immunohistochemical panel, with clinicopathologic
features and outcome. PAX8 was negative in 30 (83.3%), and SATB2 was negative in
32/35. HNF1B, AMACR, and napsin-A were detected in 33 (91.7%), 35 (97.2%), and 0
(0%), respectively. MMR proteins and ARID1A were retained in 100%; PTEN was lost
in 4 (11.1%). P53 was aberrant in 10 (27.8%); none overexpressed p16. HER2 was
positive in 6/35 (17.1%). Most PMOCs had a favorable outcome. However, recurrence
is usually fatal. The typical tumor profile was CK7+, CK20+/-, CDX2+/-, PAX8-, ER
, PgR-, and SATB2-. HER2 positivity suggests a possible target for therapy in
advanced disease.
PMID- 29338554
TI - Site Specific Evaluation of Lymphatic Vessel Sclerosis in Lower Limb Lymphedema
Patients.
AB - BACKGROUND: Histological changes in the collecting lymphatics in patients with
lymphedema are classified as Normal type, Ectasis type, Contraction type, and
Sclerosis type (NECST) classification. In this study, we investigated the
condition of the lymphatic vessels in different sites of the legs. PATIENTS AND
METHODS: We prospectively investigated the lymphatic vessels of patients with
lymphedema who underwent lymphaticovenous anastomosis (LVA) from August 8, 2014
to August 4, 2015 based on the NECST classification. Lymphedema was diagnosed
using lymphoscintigraphy, indocyanine green (ICG) lymphography, and the
International Society of Lymphology (ISL) Classification. The affected limbs were
divided into four sites: proximal thigh (Site 1), distal thigh (Site 2), proximal
crus (Site 3), and distal crus (Site 4). RESULTS: A total of 109 patients (205
limbs and 1028 lymphatics) were included in this study. Of the 109 patients,
there were 100 women and 9 men with an average age of 61 years. The ratio of
Ectasis type vessels increased toward the distal end of the limb with the highest
occurrence rate being 54% at Site 4. As ISL stage, ICG stage, and
lymphoscintigraphy stage advanced, so too did the ratio of Sclerosis type. In
secondary lymphedema patients with lymphedema, the ratio of Ectasis type was more
predominant in the distal end of the limb, whereas this tendency was not observed
in primary lymphedema patients. CONCLUSIONS: Sclerotic lymphatics are more
predominantly found in the proximal limb whereas nonsclerotic vessels are more
often found toward the distal end. These findings help lymphatic surgeon
determine incision sites.
PMID- 29338555
TI - Positive Neighborhood Norms Buffer Ethnic Diversity Effects on Neighborhood
Dissatisfaction, Perceived Neighborhood Disadvantage, and Moving Intentions.
AB - Positive neighborhood norms, such as strong local networks, are critical to
people's satisfaction with, perceived disadvantage of, and intentions to stay in
their neighborhood. At the same time, local ethnic diversity is said to be
detrimental for these community outcomes. Integrating both frameworks, we tested
whether the negative consequences of diversity occur even when perceived social
norms are positive. Study 1 ( N = 1,760 German adults) showed that perceptions of
positive neighborhood norms buffered against the effects of perceived diversity
on moving intentions via neighborhood satisfaction and perceived neighborhood
disadvantage. Study 2 ( N = 993 Dutch adults) replicated and extended this
moderated mediation model using other characteristics of diversity (i.e.,
objective and estimated minority proportions). Multilevel analyses again revealed
consistent buffering effects of positive neighborhood norms. Our findings are
discussed in light of the ongoing public and political debate concerning
diversity and social and communal life.
PMID- 29338556
TI - Hong Kong Liberals Are WEIRD: Analytic Thought Increases Support for Liberal
Policies.
AB - This study tests whether liberals and conservatives within the same society think
as if they were from different cultures. I tested this by measuring the cultural
thought style of social liberals and conservatives in Hong Kong (Study 1).
Liberals tended to think more analytically (more "WEIRD"), and conservatives
tended to think more holistically (more common in East Asia). In Study 2, I
trained people to think analytically or holistically before they read articles on
political issues. Analytic thought caused people to form more liberal opinions,
and holistic thought caused people to form more conservative opinions. The
thought training affected participants' responses to a social issue, but not an
economic issue or whether they identified as liberal or conservative. This study
replicates a previous U.S. finding in an East Asian culture and a different
political environment, suggesting that the link between politics and thought
style extends beyond the United States.
PMID- 29338557
TI - Biosynthesis, characterization and leishmanicidal activity of a biocomposite
containing AgNPs-PVP-glucantime.
AB - AIM: Development of functionalized nanocomposites containing AgNPs-PVP
Glucantime(r) to evaluate their leishmanicidal activity as a novel method for
improving the pharmacological properties of the drug Glucantime(r) against
extracellular promastigotes and intracellular amastigotes of Leishmania
amazonensis in vitro to treat cutaneous leishmaniasis. MATERIALS & METHODS: The
silver nanoparticles and nanocomposites prepared containing silver nanoparticles,
polyvinylpyrrolidone and different amounts of Glucantime were characterized using
transmission electron microscopy, x-ray diffraction, energy-dispersive x-ray
spectroscopy and zeta potential analysis; in addition, the in vitro cytotoxicity
was evaluated. RESULTS: The nanocomposites showed an inhibitory effect on the
cellular viability of promastigote forms, with values of 47.06, 51.71 and 65.67%
for nanocomposite1, nanocomposite2 and nanocomposite3, respectively, as well as a
dose-dependent decrease in the infectivity index, with values of 33.33 and 23%
for nanocomposite2 and nanocomposite3, respectively. CONCLUSION: The proposed
nanocomposite reveals leishmanial activity and the absence of cytotoxicity in
macrophages. Further investigations will be conducted in vivo.
PMID- 29338558
TI - The Influence of Masculine Norms and Occupational Factors on Mental Health:
Evidence From the Baseline of the Australian Longitudinal Study on Male Health.
AB - Men employed in male-dominated occupations are at elevated risk of work-related
fatalities, injuries, and suicide. Prior research has focused on associations
between psychosocial and physical exposures at work and health outcomes. However,
masculine norms may also contribute to mental health. We used data from the
baseline survey of the Australian Longitudinal Study on Male Health to examine
whether: (a) men in male-dominated jobs report greater adherence to masculine
norms; (b) being in a male-dominated occupation is associated with poorer mental
health; and (c) being in a male-dominated occupation modifies the association
between masculine norms and mental health. Masculine norms were measured using
the Conformity to Masculine Norms Inventory (CMNI-22). Mental health was assessed
using the SF-12. Results of regression analysis (adjusted for covariates) suggest
a linear relationship between the extent to which an occupation is male-dominated
and endorsement of values on the CMNI-22. Many CMNI-22 subscales were related to
poorer mental health. However, the need for self-reliance was identified as the
strongest predictor of poorer mental health. The mental health scale did not
appear to be patterned by occupational gender composition and we did not find an
interaction between the gender ratio of an occupation and the CNMI-22 scale.
These findings highlight the need to address harmful aspects of masculinity as a
potential cause of mental health problems. More longitudinal research is needed
on the social domains in which gender and health are experienced, such as in the
workplace.
PMID- 29338559
TI - How can 3D printing be a powerful tool in nanomedicine?
PMID- 29338560
TI - Scientists, Instruments, and Even Brains in Transfer: German-Spanish Postwar
Networks and the Construction of the Neuroendocrine System (1952-1960).
AB - This article presents the process of relocation of hegemonies and "center
periphery" dynamics in neuroanatomy after World War II through the study of the
links between the Spanish anatomical school of Jose Escolar Garcia and some
German institutions. We have analyzed their works on the morphology of the
neuroendocrine system as a case study, showing how the first contacts of the
Spaniards with the United States started a material transfer process between
centers on both sides of the Atlantic Ocean through the mediation-and adaptation
of the periphery. The case also shows how scientific networks in the "new" Europe
were reestablished after the Nazi era and how important these systems were for
the transfer of knowledge, using them for the circulation of experts,
instruments, and even biological samples.
PMID- 29338561
TI - Menopause and cardiovascular disease.
AB - Cardiovascular disease is very common in women. It is still under diagnosed and
under treated. Many women are not having their risk factors for cardiovascular
disease properly addressed. Many healthcare professionals are uncertain about the
role of hormones in cardiovascular disease. This article gives an overview of the
most important risk factors for cardiovascular disease and how to manage those
risk factors appropriately, based on the available evidence.
PMID- 29338562
TI - Targeted microbubbles with ultrasound irradiation and PD-1 inhibitor to increase
antitumor activity in B-cell lymphoma.
AB - AIM: Severe cardiac toxicity of doxorubicin and an immunosuppressive tumor micro
environment become main obstacles for the effective treatment of B-cell lymphoma.
In this research, rituximab-conjugated and doxorubicin-loaded microbubbles (RDMs)
were designed for exploring a combination approach of targeted microbubbles with
ultrasound (US) irradiation and PD-1 inhibitor to overcome obstacles mentioned
above. METHODS: In vivo studies were performed on SU-DHL-4 cell-grafted mice and
ex vivo studies were performed on CD20+ human SU-DHL-4 cells and human T cells.
RESULTS: A greater therapeutic effect and higher expression of PD-L1 protein
expression were obtained with RDMs with US irradiation in vivo. A significant
inhibitory effect on SU-DHL-4 B-cell lymphoma cells was observed after treated by
RDMs with US irradiation and PD-1 inhibitor ex vivo. CONCLUSION: Combination of
RDMs with US irradiation and PD-1 inhibitor could be a promising therapeutic
strategy for B-cell lymphoma.
PMID- 29338564
TI - 1986, The Michael Faraday prize and the promotion of science in the nineteenth
century.
PMID- 29338563
TI - The Long-Term Effects of the Youth Crime Prevention Program "New Perspectives" on
Delinquency and Recidivism.
AB - New Perspectives (NP) aims to prevent persistent criminal behavior. We examined
the long-term effectiveness of NP and whether the effects were moderated by
demographic and delinquency factors. At-risk youth aged 12 to 19 years were
randomly assigned to the intervention group (NP, n = 47) or care as usual (CAU, n
= 54). Official and self-report data were collected to assess recidivism. NP was
not more effective in reducing delinquency levels and recidivism than CAU. Also,
no moderator effects were found. The overall null effects are discussed,
including further research and policy implications.
PMID- 29338565
TI - Associations of the lipid genetic variants Thr54 ( FABP2) and -493T ( MTTP) with
total cholesterol and low-density lipoprotein cholesterol levels in Mexican
subjects.
AB - Objective Mexico has one of the world's highest rates of obesity, which is
influenced by lipid-genetic and lifestyle factors. This study aimed to determine
whether FABP2 (Ala54Thr) and MTTP (-493 G/T) genetic polymorphisms are associated
with metabolic disorders in Mexican subjects. Methods A total of 523 subjects
participated in a cross-sectional study. Genotyping for FABP2 and MTTP was
performed using real-time RT-PCR. Biochemical and anthropometric data were
evaluated. Results The genetically at-risk group (Thr54/-493T) was associated
with significantly higher total and low-density lipoprotein cholesterol levels
(difference between genetically at-risk group and wild-type group: 10.6 mg/dL and
8.94 mg/dL, respectively). Carriers within the genetically at-risk group had a
significantly higher prevalence rate of hypercholesterolaemia (42.5% vs. 32.0%)
and higher LDL-C levels (37.6% vs. 26.4%) than did non-carriers. Conclusions
Subjects who are genetically at risk (Thr54/-493T) have higher total cholesterol
levels, low-density lipoprotein cholesterol levels, and prevalence rate of
hypercholesterolaemia. These findings highlight the importance of basing
nutritional intervention strategies for preventing and treating chronic diseases
on individual genetic characteristics.
PMID- 29338566
TI - Constructing heparin-modified pancreatic decellularized scaffold to improve its
re-endothelialization.
AB - Pancreas transplantation is considered as a promising therapeutic option with the
potential to cure diabetes. However, efficacy of current clinical transplantation
is limited by the donor organ. With regard to creating a functional pancreas
tissue equivalent for transplantation, vascularization remains a large obstacle.
To enhance the angiogenic properties of pancreatic decellularized scaffold,
surface modification of the vasculature was used to promote endothelialization
efficiency. In this study, an endothelialized pancreatic decellularized scaffold
was obtained through heparin modification under mild conditions. The
immobilization of heparin was performed through 1-ethyl-3-(3-dimethylaminopropyl)
carbodiimide and N-Hydroxysuccinimide. The morphology, ultra-structure and
porosity of the heparinized scaffold were characterized by toluidine blue
staining, scanning electron microscope and infrared spectrum. The adhesion,
proliferation and angiogenesis of human umbilical vein endothelial cells on
heparin-pancreatic decellularized scaffold were also researched in vitro. In vivo
transplantation was also performed to observe the location of human umbilical
vein endothelial cells and the formation of new blood vessel, which exhibited
significant differences with pancreatic decellularized scaffold group (p<0.05).
These findings indicated that the endothelialized heparin-pancreatic
decellularized scaffold may be used to solve the problem of blood supply and to
support the function of insulin-secreting cells better after in vivo
transplantation, and therefore, would be a potential candidate for pancreatic
tissue engineering.
PMID- 29338567
TI - Outcomes with lower intensity therapy in TP53-mutated acute myeloid leukemia.
PMID- 29338568
TI - Lactoferrin plus health education versus total dose infusion (TDI) of low
molecular weight (LMW) iron dextran for treating iron deficiency anemia (IDA) in
pregnancy: a randomized controlled trial.
AB - BACKGROUND: Iron deficiency anemia (IDA) is one of the most common medical
disorder disturbing pregnancies particularly in low resources countries, and
contributes significantly to morbidities and mortalities. Thus, early diagnosis
and prompt management of IDA is highly recommended. AIM: To Test the efficacy and
safety of oral lactoferrin plus health education provided by a nurse versus total
dose infusion (TDI) of low-molecular weight (LMW) iron dextran for treating IDA
in the second and third trimester of pregnancy. DESIGN: A prospective
interventional, randomized, parallel-group, single-center longitudinal study.
SETTING: Woman's Health Assiut University Hospital, Assiut, Egypt, at the
outpatient clinic and inpatient unit. It comprised 120 cases divided into two
groups as pineapple flavored lactoferrin oral sachets 100 mg twice daily with
health education (group A) and TDI of LMW iron dextran (group B). MAIN OUTCOME
MEASURES: The primary efficacy parameter was clinical improvement and the amount
of increase in hemoglobin concentration by 4 weeks after therapy, secondary
outcome measures included measurement of the rest of RBC, and iron indices, the
adverse effects related to iron therapy and the patient compliance to the
treatment. RESULTS: There was insignificant difference between both groups
regarding sociodemographic data, parity and mean gestational age. Both groups
showed a significant clinical improvement of anemia 4 weeks post-therapy. There
was no statistically significant difference in mean Hb level improvement in both
groups after 1 month of therapy. However, mean corpuscular volume (MCV) and mean
corpuscular hemoglobin (MCH) improved significantly more in group B than A while
iron indices (serum iron and serum ferritin) were significantly more in group A
than group B. CONCLUSIONS: Pineapple flavored lactoferrin oral sachets plus
health education can be widely used as an alternative to TDI iron dextran
supplementation due to clinical as well as laboratory improvement of IDA during
pregnancy after 1 month of treatment. Proper health education of the pregnant
women with nurse recommendations of balanced diet containing good sources of iron
would increase awareness of pregnant women and help eradicate IDA with its
serious sequel during pregnancy.
PMID- 29338569
TI - Death rituals, religious beliefs, and grief of Turkish women.
AB - Grief following a death loss is a common experience that all individuals face at
some point in life. There, however, are only a few in-depth studies regarding
grief in cultures around the world and specific roles that rituals and beliefs
related to death may have in the grieving process. Results of interview data from
eight grieving Turkish women revealed three themes: (a) metaphors of loss, (b)
funeral rituals, and (c) rituals in relation to control and personal factors.
Overall, participants' sense of control appeared to influence their grief
experiences and perceptions of rituals.
PMID- 29338570
TI - A Novel Rubric to Evaluate Wearable Cameras for Assessment of Interrater
Reliability.
AB - Research has reported on traditional methods of assessing interrater reliability
but, currently, no such standard protocol exists for selection of alternative
methods of assessing interrater reliability, such as wearable video cameras. The
professions of occupational therapy and occupational science take a unique
ecological perspective when evaluating individuals, which focuses on the
naturalistic perspective of an individual, ideally resulting in optimal
performance. Given current advancements in technology, wearable, low-cost,
unobtrusive, first-person view digital video cameras are readily available for
use in research. The researchers generated an original rubric for critiquing
cameras, then trialed four cameras for use in a future interrater reliability
study. This standardized protocol fills a gap in the field and can be used by
future researchers searching for a standardized method of camera selection.
PMID- 29338571
TI - Erratum.
PMID- 29338572
TI - Implementation of additional prescribing authorization among oncology pharmacists
in Alberta.
AB - Purpose To describe the practice settings and prescribing practices of oncology
pharmacists with additional prescribing authorization. Methods A descriptive,
cross-sectional survey of all oncology pharmacists in Alberta was conducted using
a web-based questionnaire over four weeks between March and April 2016.
Pharmacists were identified from the Cancer Services Pharmacy Directory and
leadership staff in Alberta Health Services. Descriptive statistics were used to
describe the practice setting, prescribing practices, motivators to apply for
additional prescribing authorization, and the facilitators and barriers of
prescribing. Logistic regression was used to explore factors associated with
having additional prescribing authorization. Results The overall response rate
was 41% (71 of 175 pharmacists). Oncology pharmacists with additional prescribing
authorization made up 38% of respondents. They primarily worked in urban,
tertiary cancer centers, and practiced in ambulatory care. The top 3 clinical
activities they participated in were medication reconciliation, medication
counseling/education, and ambulatory patient assessment. Respondents thought
additional prescribing authorization was most useful for ambulatory patient
assessment and follow-up. Antiemetics were prescribed the most often. The median
number of prescriptions written in an average week of clinical work was 5.
Competence, self-confidence, and the potential impact on patient care/perceived
impact on work environment were the strongest facilitators of prescribing. The
strongest motivators to apply for additional prescribing authorization were
relevancy to practice, the potential for increased efficiency, and advancing the
profession. Conclusion The current majority of oncology pharmacist prescribing in
Alberta occurs in ambulatory care with a large focus on antiemetic prescribing.
Pharmacists found additional prescribing authorization most useful for ambulatory
patient assessment and follow-up.
PMID- 29338573
TI - Triphenylphosphine-docetaxel conjugate-incorporated albumin nanoparticles for
cancer treatment.
AB - AIM: The objective of this study was to develop a mitochondria-targeted
anticancer drug, docetaxel (DTX), for chemotherapy. MATERIALS & METHODS: The DTX
was conjugated to 4-carboxybutyl triphenylphosphonium (TPP) to enhance
mitochondrial targeting, and the TPP-DTX conjugate was further loaded into folate
cholesteryl albumin (FA-chol-BSA) nanoparticles (NPs) to improve its
biocompatibility. RESULTS & CONCLUSION: In vitro studies showed that TPP-DTX and
its NP primarily accumulated in the mitochondria; generated high reactive oxygen
species, leading to mitochondrial disruption and cell apoptosis; and had a higher
cytotoxicity against cancer cells. In vivo antitumor studies indicated that the
NP significantly suppressed tumor growth compared with free drugs in xenograft
tumor-bearing mice. Our results demonstrated that TPP-DTX@FA-chol-BSA NPs could
be a promising mitochondria-targeted anticancer prodrug for chemotherapy.
PMID- 29338574
TI - Protein nanoparticles are nontoxic, tuneable cell stressors.
AB - AIM: Nanoparticle-cell interactions can promote cell toxicity and stimulate
particular behavioral patterns, but cell responses to protein nanomaterials have
been poorly studied. RESULTS: By repositioning oligomerization domains in a
simple, modular self-assembling protein platform, we have generated closely
related but distinguishable homomeric nanoparticles. Composed by building blocks
with modular domains arranged in different order, they share amino acid
composition. These materials, once exposed to cultured cells, are differentially
internalized in absence of toxicity and trigger distinctive cell adaptive
responses, monitored by the emission of tubular filopodia and enhanced drug
sensitivity. CONCLUSION: The capability to rapidly modulate such cell responses
by conventional protein engineering reveals protein nanoparticles as tuneable,
versatile and potent cell stressors for cell-targeted conditioning.
PMID- 29338575
TI - Characterization of medium-chain-length polyhydroxyalkanoate biosynthesis by
Pseudomonas mosselii TO7 using crude glycerol.
AB - Polyhydroxyalkanoates (PHAs) are biopolyesters produced by microorganisms that
are environmentally friendly. PHAs can be used to replace traditional plastic to
reduce environmental pollution in various fields. PHA production costs are high
because PHA must be produced from a carbon substrate. The purpose of this study
was to find the strain that can used the BDF by-product as the sole carbon source
to produce high amounts of medium-chain-length PHA. Three isolates were evaluated
for potential PHA production by using biodiesel-derived crude glycerol as the
sole carbon source. Among them, Pseudomonas mosselii TO7 yielded high PHA
content. The PHA produced from P. mosselii TO7 were medium-chain-length-PHAs. The
PHA content of 48% cell dry weight in 48 h with a maximum PHA productivity of
13.16 mg PHAs L-1 h-1. The narrow polydispersity index value of 1.3 reflected the
homogeneity of the polymer chain, which was conducive to industrial applications.
PMID- 29338576
TI - Effect of clinical response to active drugs and placebo on antipsychotics and
mood stabilizers relative efficacy for bipolar depression and mania: A meta
regression analysis.
AB - BACKGROUND: Randomised placebo-controlled trials investigating treatments for
bipolar disorder have been hampered by wide variations of active drugs and
placebo clinical response rates. It is important to estimate whether the active
drug or placebo response has a greater influence in determining the relative
efficacy of drugs for psychosis (antipsychotics) and relapse prevention (mood
stabilisers) for bipolar depression and mania. METHODS: We identified 53
randomised, placebo-controlled trials assessing antipsychotic or mood stabiliser
monotherapy ('active drugs') for bipolar depression or mania. We carried out
random-effects meta-regressions, estimating the influence of active drugs and
placebo response rates on treatment relative efficacy. RESULTS: Meta-regressions
showed that treatment relative efficacy for bipolar mania was influenced by the
magnitude of clinical response to active drugs ( p=0.002), but not to placebo (
p=0.60). On the other hand, treatment relative efficacy for bipolar depression
was influenced by response to placebo ( p=0.047), but not to active drugs (
p=0.98). CONCLUSIONS: Despite several limitations, our unexpected findings showed
that antipsychotics / mood stabilisers relative efficacy for bipolar depression
seems unrelated to active drugs response rates, depending only on clinical
response to placebo. Future research should explore strategies to reduce placebo
related issues in randomised, placebo-controlled trials for bipolar depression.
PMID- 29338577
TI - Modeling Sluggishness in Binaural Unmasking of Speech for Maskers With Time
Varying Interaural Phase Differences.
AB - In studies investigating binaural processing in human listeners, relatively long
and task-dependent time constants of a binaural window ranging from 10 ms to 250
ms have been observed. Such time constants are often thought to reflect "binaural
sluggishness." In this study, the effect of binaural sluggishness on binaural
unmasking of speech in stationary speech-shaped noise is investigated in 10
listeners with normal hearing. In order to design a masking signal with
temporally varying binaural cues, the interaural phase difference of the noise
was modulated sinusoidally with frequencies ranging from 0.25 Hz to 64 Hz. The
lowest, that is the best, speech reception thresholds (SRTs) were observed for
the lowest modulation frequency. SRTs increased with increasing modulation
frequency up to 4 Hz. For higher modulation frequencies, SRTs remained constant
in the range of 1 dB to 1.5 dB below the SRT determined in the diotic situation.
The outcome of the experiment was simulated using a short-term binaural speech
intelligibility model, which combines an equalization-cancellation (EC) model
with the speech intelligibility index. This model segments the incoming signal
into 23.2-ms time frames in order to predict release from masking in modulated
noises. In order to predict the results from this study, the model required a
further time constant applied to the EC mechanism representing binaural
sluggishness. The best agreement with perceptual data was achieved using a
temporal window of 200 ms in the EC mechanism.
PMID- 29338579
TI - Multi-spectroscopic and molecular modeling studies to reveal the interaction
between propyl acridone and calf thymus DNA in the presence of histone H1: binary
and ternary approaches.
AB - DNA is the primary target of many anticancer drugs involved in important
intercellular processes, especially in transcriptional regulation, and histone is
known to inhibit gene expression. Small molecules can bind to histone-DNA and
impair the cell division, growth, inhibition, and apoptosis in cancer cells. In
this research, the interaction of a histone H1-calf thymus DNA (ct DNA) complex
and propyl acridone (PA) was investigated in Tris-HCl buffer, pH 6.8, using multi
spectroscopic, viscosity, and molecular modeling techniques. The Stern Volmer
plot of the (H1-ct DNA) PA complex demonstrated two sets of binding sites with
various binding affinities at three different temperatures. Thermodynamic
parameters (DeltaH degrees < 0 and DeltaS degrees < 0) indicated that hydrogen
bonds and van der Waals forces played the main roles in the binding of the drug
to H1-ct DNA. The interaction between PA and ct DNA as well as (H1-ct-DNA) in the
presence of acridine orange and ethidium bromide showed two different interaction
behaviors in ternary systems. According to results from UV absorption
spectroscopy and melting temperature (Tm) measurements, the binding mode of PA
with ct DNA and the (H1-ct DNA) complex was indicative of an intercalative
binding for the binary system and of both intercalative with groove binding with
molecular fraction for the ternary system. Furthermore, the PA-induced detectable
changes in the circular dichroism spectrum of ct DNA as well as changes in its
viscosity. All of the experimental results proved that the intercalative binding
between PA and ct DNA as well as the (H1-ct DNA) complex as binary and ternary
systems must be predominant. The results obtained from experimental data were in
good agreement with molecular modeling with regard to the determination of the
binding site of PA to ct DNA in the absence and presence of histone H1.
PMID- 29338578
TI - Cannabis Use is Associated with Lower Odds of Prescription Opioid Analgesic Use
Among HIV-Infected Individuals with Chronic Pain.
AB - BACKGROUND: Chronic pain is common in the United States and prescribed opioid
analgesics use for noncancer pain has increased dramatically in the past two
decades, possibly accounting for the current opioid addiction epidemic. Co-morbid
drug use in those prescribed opioid analgesics is common, but there are few data
on polysubstance use patterns. OBJECTIVE: We explored patterns of use of
cigarette, alcohol, and illicit drugs in HIV-infected people with chronic pain
who were prescribed opioid analgesics. METHODS: We conducted a secondary data
analysis of screening interviews conducted as part of a parent randomized trial
of financial incentives to improve HIV outcomes among drug users. In a
convenience sample of people with HIV and chronic pain, we collected self-report
data on demographic characteristics; pain; patterns of opioid analgesic use (both
prescribed and illicit); cigarette, alcohol, and illicit drug use (including
cannabis, heroin, and cocaine) within the past 30 days; and current treatment for
drug use and HIV. RESULTS: Almost half of the sample of people with HIV and
chronic pain reported current prescribed opioid analgesic use (N = 372, 47.1%).
Illicit drug use was common (N = 505, 63.9%), and cannabis was the most commonly
used illicit substance (N = 311, 39.4%). In multivariate analyses, only cannabis
use was significantly associated with lower odds of prescribed opioid analgesic
use (adjusted odds ratio = 0.57; 95% confidence interval: 0.38-0.87).
Conclusions/Importance: Our data suggest that new medical cannabis legislation
might reduce the need for opioid analgesics for pain management, which could help
to address adverse events associated with opioid analgesic use.
PMID- 29338580
TI - Paeonol nanoemulsion for enhanced oral bioavailability: optimization and
mechanism.
AB - AIM: The aim of this work was to optimize a nanoemulsion formulation and explain
its absorption mechanism in improving the oral bioavailability of paeonol.
METHOD: The bioavailability of paeonol was compared between paeonol nanoemulsion
group and paeonol suspension group. The in situ single-pass intestine perfusion
method, in vitro everted gut sacs method, Western blot analysis and Caco-2 cell
transport studies were used to investigate the absorption mechanism of
nanoemulsion. RESULTS: Nanoemulsion was proved to enhance the bioavailability of
paeonol. P-glycoprotein (P-gp) mediated efflux might be the main reason affecting
the oral absorption of paeonol. The prepared nanoemulsion prevented the P-gp
mediated efflux and enhanced the bioavailability of paeonol. CONCLUSION: The
overall results revealed that nanoemulsion was an effective vehicle to improve
the oral bioavailability of paeonol which resulted from the prevention of P-gp
efflux probably.
PMID- 29338581
TI - Perceived Discrimination as a Risk Factor for Use of Emerging Tobacco Products:
More Similarities Than Differences Across Demographic Groups and Attributions for
Discrimination.
AB - BACKGROUND: Perceived discrimination has been associated with cigarette smoking
and other substance use among members of disadvantaged minority groups. However,
most studies have focused on a single minority group, have not considered the
individual's attribution for the discrimination, and have not considered emerging
tobacco products. OBJECTIVE: This study examined the associations between
perceived discrimination and use of six tobacco products (cigarettes, e
cigarettes, cigars, pipe tobacco, hookah, and smokeless tobacco) in a diverse
sample of 1,068 adults in the United States. METHODS: Participants were recruited
on Amazon's Mechanical Turk and participated in an online survey. Logistic
regression models were used to examine the association between perceived
discrimination and use of each tobacco product. Interactions between
discrimination and demographic characteristics, and between discrimination and
perceived reasons for discrimination, were evaluated. RESULTS: Controlling for
age, sex, race/ethnicity, education, and socioeconomic status, perceived
discrimination was a risk factor for current use of five of the six tobacco
products. These associations were consistent across racial/ethnic groups and
regardless of the individual's attribution for the reason for the discrimination.
CONCLUSIONS: Results indicate that perceived discrimination is a risk factor for
the use of multiple tobacco products, and that this association is not limited to
particular demographic groups or types of discrimination. Public health programs
could potentially reduce tobacco-related disease by teaching healthier ways to
cope with discrimination.
PMID- 29338582
TI - A human pericardium biopolymeric scaffold for autologous heart valve tissue
engineering: cellular and extracellular matrix structure and biomechanical
properties in comparison with a normal aortic heart valve.
AB - The objective of our study was to compare the cellular and extracellular matrix
(ECM) structure and the biomechanical properties of human pericardium (HP) with
the normal human aortic heart valve (NAV). HP tissues (from 12 patients) and NAV
samples (from 5 patients) were harvested during heart surgery. The main cells in
HP were pericardial interstitial cells, which are fibroblast-like cells of
mesenchymal origin similar to the valvular interstitial cells in NAV tissue. The
ECM of HP had a statistically significantly (p < 0.001) higher collagen I
content, a lower collagen III and elastin content, and a similar
glycosaminoglycans (GAGs) content, in comparison with the NAV, as measured by ECM
integrated density. However, the relative thickness of the main load-bearing
structures of the two tissues, the dense part of fibrous HP (49 +/- 2%) and the
lamina fibrosa of NAV (47 +/- 4%), was similar. In both tissues, the secant
elastic modulus (Es) was significantly lower in the transversal direction (p <
0.05) than in the longitudinal direction. This proved that both tissues were
anisotropic. No statistically significant differences in UTS (ultimate tensile
strength) values and in calculated bending stiffness values in the longitudinal
or transversal direction were found between HP and NAV. Our study confirms that
HP has an advantageous ECM biopolymeric structure and has the biomechanical
properties required for a tissue from which an autologous heart valve replacement
may be constructed.
PMID- 29338583
TI - Endocannabinoid engagement of CB2 regulates RSV-induced immunity.
PMID- 29338584
TI - Effect of acute ingestion of beta-hydroxybutyrate salts on the response to graded
exercise in trained cyclists.
AB - Acute ingestion of ketone salts induces nutritional ketosis by elevating beta
hydroxybutyrate (betaHB), but few studies have examined the metabolic effects of
ingestion prior to exercise. Nineteen trained cyclists (12 male, 7 female)
undertook graded exercise (8 min each at ~30%, 40%, 50%, 60%, 70%, and 80%
VO2peak) on a cycle ergometer on two occasions separated by either 7 or 14 days.
Trials included ingestion of boluses of either (i) plain water (3.8 mL kg body
mass-1) (CON) or (ii) betaHB salts (0.38 g kg body mass-1) in plain water (3.8 mL
kg body mass-1) (KET), at both 60 min and 15 min prior to exercise. During KET,
plasma [betaHB] increased to 0.33 +/- 0.16 mM prior to exercise and 0.44 +/- 0.15
mM at the end of exercise (both p < .05). Plasma glucose was 0.44 +/- 0.27 mM
lower (p < .01) 30 min after ingestion of KET and remained ~0.2 mM lower
throughout exercise compared to CON (p < .001). Respiratory exchange ratio (RER)
was higher during KET compared to CON (p < .001) and 0.03-0.04 higher from
30%VO2peak to 60%VO2peak (all p < .05). No differences in plasma lactate, rate of
perceived exertion, or gross or delta efficiency were observed between trials.
Gastrointestinal symptoms were reported in 13 out of 19 participants during KET.
Acute ingestion of betaHB salts induces nutritional ketosis and alters the
metabolic response to exercise in trained cyclists. Elevated RER during KET may
be indicative of increased ketone body oxidation during exercise, but at the
plasma betaHB concentrations achieved, ingestion of betaHB salts does not affect
lactate appearance, perceived exertion, or muscular efficiency.
PMID- 29338585
TI - The Effects of a Nutrition Media Literacy Intervention on Parents' and Youths'
Communication about Food.
AB - Interventions addressing links between media exposure and obesity risk for school
age youth have not explicitly addressed the role of family communication about
media. Youths' influence attempts on parents to purchase advertised foods can
create conflict and negatively affect parental food choices. This study tested
whether a family-based media literacy curriculum improves parents' media
management skills and decreases youths' susceptibility to appealing but
unrealistic food marketing. A matched-group pretest/posttest field experiment of
parent-youth dyads with control group (N = 100 dyads, youth M = 11 years of age)
tested the six-session curriculum. Hypotheses were analyzed using a Bayesian
structural equation model. The curriculum increased parents' active negative
mediation to foster youths' critical thinking about food marketing, b* = 0.35,
95% CCI [0.17, 0.50], increased parent Efficacy for making healthy dietary
changes for their families, b* = 0.59, 95% CCI [0.41, 0.75], and fostered family
discussion about nutrition labels (total effect = 0.22). Additionally, cumulative
influences of Perceived Desirability and Wishful Identification on youths'
requests for marketed foods were reduced (total effect = 0.04). Media literacy
education can empower parents and improve youths' critical thinking to reduce
effects of food marketing on families and improve use of media to obtain
nutrition information.
PMID- 29338586
TI - Association of CXCL13 serum level and ultrasonographic findings of joints in
patients with systemic lupus erythematosus and Jaccoud's arthropathy.
AB - Objectives The objective of this paper is to perform an ultrasonography (US)
analysis of hands and wrists in two groups of patients with systemic lupus
erythematosus (SLE), with and without Jaccoud's arthropathy, matched by age and
disease duration and to correlate them with levels of CXCL13 clinical features,
laboratory tests and disease activity score. Methods Sixty-four patients with SLE
were enrolled, 32 with and 32 without Jaccoud's arthropathy. Each patient
underwent physical examination, laboratory tests (including CXCL13 by ELISA) and
bilateral US. Synovial hypertrophy, tenosynovitis and erosions were evaluated
according to a semiquantitative grading system with a 0-3 rating. US findings
were correlated with serum levels of CXCL13, other serological parameters and
disease activity index. Results Synovitis was found in 25/64 patients (39%) and
tenosynovitis in 14/64 (22%). These findings were more frequent in SLE patients
with Jaccoud's arthropathy, particularly tenosynovitis ( p = 0.002) and synovitis
( p = 0.01). Median serum level of CXCL13 was 20.16 pg/ml in the whole population
(23.21 pg/ml in the Jaccoud's arthropathy group and 11.48 pg/ml in the group
without). There was an association between the presence of disease activity and
high level of CXCL13 ( p = 0.004). However, no association was found between high
levels of CXCL13 and "arthritis" in SLEDAI, swollen joints on physical
examination or synovitis on US. Conclusions US findings in joints of SLE patients
with Jaccoud's arthropathy confirm that synovitis and tenosynovitis are common in
these patients. In addition, serum level of CXCL13 is associated with disease
activity in SLE but does not seem to be a biomarker for arthritis in these
patients.
PMID- 29338587
TI - Antiphosphatidylserine/prothrombin (aPS/PT) antibodies are associated with
Raynaud phenomenon and migraine in primary thrombotic antiphospholipid syndrome.
AB - Objectives Antibodies to phosphatidylserine/prothrombin complex (aPS/PT)
detectable in sera of some patients with antiphospholipid syndrome (APS) have
been shown to correlate with thrombosis. However, associations of aPS/PT
antibodies with APS related disorders remain unclear. Aim To evaluate whether
there are any associations between aPS/PT antibodies and Raynaud phenomenon,
migraine and/or valvular lesions in primary thrombotic APS (PAPS). Methods We
enrolled 67 consecutive patients (56 women) with thrombotic PAPS (VTE in 80.6%),
aged 46.2 +/- 13.5 years. The exclusion criteria were: acute coronary syndromes
or stroke within preceding 6 months, cancer, severe comorbidities and pregnancy.
The IgG and IgM aPS/PT antibodies were determined by ELISA with the cut-off of 30
units. We recorded Raynaud phenomenon, migraine and valvular lesions. Results
Positive IgM or/and IgG aPS/PT antibodies were observed in 29 patients (43.3%),
with a higher prevalence of IgM antibodies ( n = 27, 40.3%) compared with IgG
isotype ( n = 12, 17.9%, p = 0.014). aPS/PT antibodies were observed most
commonly in patients with triple aPL ( n = 12, 85.7%) compared with those with
double ( n = 5, 35.7%) or single aPL antibodies (n = 12, 30.8%, p = 0.03), with
no association with demographics, the ANA titre, the type of thrombotic events or
medications. Raynaud phenomenon, migraine and valvular lesions were observed in
15% ( n = 10), 30% ( n = 20) and 18% ( n = 12) of the patients, respectively.
Raynaud phenomenon and migraine, but not valvular lesions, were markedly more
frequent in PAPS patients presenting with positive aPS/PT antibodies ( n = 10,
34.5% vs. n = 0, 0%; p = 0.0001). Conclusions In PAPS patients aPS/PT antibodies
are related to the occurrence of both Raynaud phenomenon and migraine.
PMID- 29338588
TI - Epstein-Barr virus infection and type I interferon signature in patients with
systemic lupus erythematosus.
AB - Epstein-Barr (EB) virus infection has long been speculated to evoke systemic
lupus erythematosus (SLE). Since a virus infection can induce interferon (IFN)
system activation, we aimed to discover the relationship between the two in the
progression of SLE in a Chinese inpatient cohort. Methods Peripheral blood
mononuclear cells and sera were isolated from 116 SLE patients and 76 healthy
controls. Antibodies against EBV-VCA (IgM and IgG) and EBNA (IgG) along with
IFNalpha in patient sera were detected with enzyme-linked immunosorbent assays.
The EB virus DNA load was detected by real-time quantitative polymerase chain
reaction. Peripheral blood mononuclear cells both from patients and controls were
isolated immediately. The mRNA from these samples was subjected to real-time PCR
for the latent genes EBNA1, EBNA2 and LMP1 of EB virus, as well as four IFN
stimulated genes (ISGs) ( OASL, MX1, ISG15 and LY6E). The antibody results were
used to determine the stage of EBV infection (lytic, latent, or previous).
Results SLE patients had a higher rate of lytic infection defined as positive EBV
VCA IgM antibody (39.66% vs 10.53%, p = 0.027), but not the EB virus DNA load.
Patients with lytic EB virus infection had higher SLEDAI scores than patients
with non-lytic infection (15.24 +/- 2.63 vs 13.79 +/- 3.24, p = 0.012). LMP1 was
the only EBV gene that had a higher expression level in SLE patients than in
healthy controls (3.26 +/- 2.95 vs 1.00 +/- 2.89, p = 0.000). It was also
positively correlated with SLEDAI scores ( r = 0.462, p = 0.000). Levels of
IFNalpha and the four ISGs were all significantly higher in SLE patients than in
healthy controls ( p < 0.05). LMP1 was positively correlated with the four ISGs (
r = 0.403 ~ 0.494, p < 0.05) in SLE patients but not in healthy controls ( r =
0.153 ~ 0.129, p > 0.05). Neither EBNA1 nor EBNA2 was correlated with the ISGs in
SLE patients or in healthy controls. Conclusions The SLE patients had higher
rates of lytic EB virus infection and higher latent gene LMP1 expression, which
might be associated with the development and/or the progression of SLE via the
type I IFN pathway. The underlying mechanism needs more study.
PMID- 29338589
TI - Population Health: School Health Services and School Nursing.
PMID- 29338590
TI - Histopathology and Antibodies.
PMID- 29338591
TI - Association between health status and sociodemographic, clinical and treatment
disparities in the Patient-centered Outcomes Related to TReatment Practices in
Peripheral Arterial Disease: Investigating Trajectories (PORTRAIT) registry.
AB - Patients with peripheral artery disease (PAD) and intermittent claudication (IC)
have impaired functional status and quality of life. However, little is known
about which factors are associated with poorer health status at the time of
initial presentation for PAD specialty care. Characterization of such features
might provide insight into disparities that impact health status in this
population. A total of 1258 patients from the United States, the Netherlands and
Australia with new or worsened IC were enrolled at their first PAD specialty care
visit between June 2011 and December 2015. The mean Peripheral Artery
Questionnaire (PAQ) Summary Score (range 0-100), a disease-specific health status
measure, was 49.2 +/- 21.9. Hierarchical, multivariable linear regression was
used to relate patient characteristics to baseline PAQ. Patient characteristics
independently associated with poorer health status were age ( p < 0.001), female
sex ( p < 0.001), not being married ( p = 0.02), economic burden (moderate/severe
vs none, moderate/severe vs some; p = 0.03), difficulty getting care
(moderate/severe vs none, moderate/severe vs some; p < 0.001), chronic lung
disease ( p = 0.02), back pain ( p < 0.001), bilateral vs unilateral PAD ( p =
0.02), intermittent claudication severity (moderate vs mild, severe vs mild, p <
0.001), and lack of prior participation in an exercise program ( p = 0.005).
Disparities in both vascular and non-vascular factors were associated with
patients' health status at the time of presentation and should be addressed by
all who care for patients with vascular disease.
PMID- 29338592
TI - Whole-Genome-Sequencing characterization of bloodstream infection-causing
hypervirulent Klebsiella pneumoniae of capsular serotype K2 and ST374.
AB - Hypervirulent K. pneumoniae variants (hvKP) have been increasingly reported
worldwide, causing metastasis of severe infections such as liver abscesses and
bacteremia. The capsular serotype K2 hvKP strains show diverse multi-locus
sequence types (MLSTs), but with limited genetics and virulence information. In
this study, we report a hypermucoviscous K. pneumoniae strain, RJF293, isolated
from a human bloodstream sample in a Chinese hospital. It caused a metastatic
infection and fatal septic shock in a critical patient. The microbiological
features and genetic background were investigated with multiple approaches. The
Strain RJF293 was determined to be multilocis sequence type (ST) 374 and serotype
K2, displayed a median lethal dose (LD50) of 1.5 * 102 CFU in BALB/c mice and was
as virulent as the ST23 K1 serotype hvKP strain NTUH-K2044 in a mouse lethality
assay. Whole genome sequencing revealed that the RJF293 genome codes for 32
putative virulence factors and exhibits a unique presence/absence pattern in
comparison to the other 105 completely sequenced K. pneumoniae genomes. Whole
genome SNP-based phylogenetic analysis revealed that strain RJF293 formed a
single clade, distant from those containing either ST66 or ST86 hvKP. Compared to
the other sequenced hvKP chromosomes, RJF293 contains several strain-variable
regions, including one prophage, one ICEKp1 family integrative and conjugative
element and six large genomic islands. The sequencing of the first complete
genome of an ST374 K2 hvKP clinical strain should reinforce our understanding of
the epidemiology and virulence mechanisms of this bloodstream infection-causing
hvKP with clinical significance.
PMID- 29338594
TI - Cancer therapeutics through an evolutionary lens.
PMID- 29338593
TI - Expression and role of granulocyte macrophage colony-stimulating factor receptor
(GM-CSFR) and granulocyte colony-stimulating factor receptor (G-CSFR) on Ph
positive acute B lymphoblastic leukemia.
AB - OBJECTIVE: We observed that ph + ALL patients administrated with recombinant
human G-CSF (rhG-CSF) after intense chemotherapy have presented a trend of
disease relapse. Thus, we aim to thoroughly investigate the expression and role
of GM-CSFR and G-CSFR on ph + ALL patients. METHOD: SUP-B15, BALL-1 and primary
leukemia cells were used in this study. Transcript levels were analyzed by
quantitative PCR while cell viability was measured using a CCK-8 assay. Flow
cytometry was used to assess the different stages of cell cycle. RESULTS: We
found that the mRNA expression levels of GM-CSFR and G-CSFR were higher in
patients with ph + ALL, as well as in SUP-B15 cells. rhG-CSF was also observed to
promote the viability of SUP-B15 cells while inversely inhibiting BALL-1 cell
viability. In addition, we also determined that rhG-CSF (100 ng/ml) decreased the
sensitivity of SUP-B15 cells to imatinib and nilotinib, while the results were
exactly the contrary for dasatinib. CONCLUSION: We demonstrated high expression
levels of GM-CSFR and G-CSFR, as well as their promotable role for viability in
ph + ALL cells. We further found that rhG-CSF influenced the sensitivity of SUP
B15 cells to TKIs.
PMID- 29338595
TI - From NHS to devolved independent regional health services.
PMID- 29338597
TI - Imagine ... a better future for the NHS.
PMID- 29338598
TI - Using randomised, double-blind, N-of-1 trials of food challenge to diagnose food
allergy and assess the effectiveness of food allergen avoidance.
PMID- 29338601
TI - Reflections on the development of a therapeutic recreation-based bereavement camp
for families whose child has died from serious illness.
AB - While bereavement camps serve as a support for children, this study examines a
therapeutic recreation-based camp for families who have lost a child. The study
triangulated documents, researcher reflection, and staff interviews to highlight
the themes of Searching & Finding, Getting to Know, Finding the Balance, and
Joining. Developing opportunistically through internal and external factors, the
camp's evolution represents a closing of the loop, from supporting families of
living children to also supporting the families of children who have died.
Understanding the camp's evolution may facilitate other programs by highlighting
the challenges in developing the program and the lessons learned.
PMID- 29338603
TI - Emerging roles of inositol pyrophosphates as key modulators of fungal
pathogenicity.
AB - Inositol pyrophosphates (PP-IPs) are energy-rich small molecules that are
omnipresent in eukaryotic cells, from yeast to mammals, playing central roles in
overall cellular homeostasis as a diverse and multifaceted class of intracellular
messengers. Recent studies of the metabolic pathways and physiological roles of
PP-IPs in the human pathogenic fungus Cryptococcus neoformans have revealed that
the PP-IP5 (IP7) is a key metabolite essential for fungal metabolic adaptation to
the host environment, immune recognition, and pathogenicity. This suggests the PP
IP biosynthesis pathway, comprising phospholipase C1 (Plc1) and a series of
sequentially acting inositol polyphosphate kinases (IPKs), as a new virulence
related signaling pathway in C. neoformans. Given that fungal species have a
reduced array of the kinases required for the synthesis of PP-IPs and that the
homology between human and fungal IPKs is restricted to a few catalytically
important residues, identification of IPK inhibitors specifically targeting the
kinases of pathogenic fungi has emerged as a desirable and achievable strategy
for antifungal drug development.
PMID- 29338602
TI - Sequential drug treatment algorithm for agitation and aggression in Alzheimer's
and mixed dementia.
AB - INTRODUCTION: Behavioural and psychological symptoms of dementia (BPSD) include
agitation and aggression in people with dementia. BPSD is common on inpatient
psychogeriatric units and may prevent individuals from living at home or in
residential/nursing home settings. Several drugs and non-pharmacological
treatments have been shown to be effective in reducing behavioural and
psychological symptoms of dementia. Algorithmic treatment may address the
challenge of synthesizing this evidence-based knowledge. METHODS: A
multidisciplinary team created evidence-based algorithms for the treatment of
behavioural and psychological symptoms of dementia. We present drug treatment
algorithms for agitation and aggression associated with Alzheimer's and mixed
Alzheimer's/vascular dementia. Drugs were appraised by psychiatrists based on
strength of evidence of efficacy, time to onset of clinical effect, tolerability,
ease of use, and efficacy for indications other than behavioural and
psychological symptoms of dementia. RESULTS: After baseline assessment and
discontinuation of potentially exacerbating medications, sequential trials are
recommended with risperidone, aripiprazole or quetiapine, carbamazepine,
citalopram, gabapentin, and prazosin. Titration schedules are proposed, with
adjustments for frailty. Additional guidance is given on use of electroconvulsive
therapy, optimization of existing cholinesterase inhibitors/memantine, and use of
pro re nata medications. CONCLUSION: This algorithm-based approach for drug
treatment of agitation/aggression in Alzheimer's/mixed dementia has been
implemented in several Canadian Hospital Inpatient Units. Impact should be
assessed in future research.
PMID- 29338605
TI - Noteworthy Literature published in 2017 for Cardiac Critical Care.
AB - In 2017, many high-impact articles appeared in the literature. This is the third
edition of an annual review of articles related to postoperative cardiac critical
care that may affect the cardiac anesthesiologist. This year explores vasopressor
and inotropic support, timing of renal replacement therapy, management of
postoperative respiratory insufficiency, and targeted temperature therapy.
PMID- 29338604
TI - Clinical significance of cerebral microbleeds on MRI: A comprehensive meta
analysis of risk of intracerebral hemorrhage, ischemic stroke, mortality, and
dementia in cohort studies (v1).
AB - Background Cerebral microbleeds can confer a high risk of intracerebral
hemorrhage, ischemic stroke, death and dementia, but estimated risks remain
imprecise and often conflicting. We investigated the association between cerebral
microbleeds presence and these outcomes in a large meta-analysis of all published
cohorts including: ischemic stroke/TIA, memory clinic, "high risk" elderly
populations, and healthy individuals in population-based studies. Methods Cohorts
(with > 100 participants) that assessed cerebral microbleeds presence on MRI,
with subsequent follow-up (>=3 months) were identified. The association between
cerebral microbleeds and each of the outcomes (ischemic stroke, intracerebral
hemorrhage, death, and dementia) was quantified using random effects models of
(a) unadjusted crude odds ratios and (b) covariate-adjusted hazard rations.
Results We identified 31 cohorts ( n = 20,368): 19 ischemic stroke/TIA ( n =
7672), 4 memory clinic ( n = 1957), 3 high risk elderly ( n = 1458) and 5
population-based cohorts ( n = 11,722). Cerebral microbleeds were associated with
an increased risk of ischemic stroke (OR: 2.14; 95% CI: 1.58-2.89 and adj-HR:
2.09; 95% CI: 1.71-2.57), but the relative increase in future intracerebral
hemorrhage risk was greater (OR: 4.65; 95% CI: 2.68-8.08 and adj-HR: 3.93; 95%
CI: 2.71-5.69). Cerebral microbleeds were an independent predictor of all-cause
mortality (adj-HR: 1.36; 95% CI: 1.24-1.48). In three population-based studies,
cerebral microbleeds were independently associated with incident dementia (adj
HR: 1.35; 95% CI: 1.00-1.82). Results were overall consistent in analyses
stratified by different populations, but with different degrees of heterogeneity.
Conclusions Our meta-analysis shows that cerebral microbleeds predict an
increased risk of stroke, death, and dementia and provides up-to-date effect
sizes across different clinical settings. These pooled estimates can inform
clinical decisions and trials, further supporting cerebral microbleeds role as
biomarkers of underlying subclinical brain pathology in research and clinical
settings.
PMID- 29338606
TI - Utility of mean sphered cell volume and mean reticulocyte volume for the
diagnosis of hereditary spherocytosis.
AB - INTRODUCTION: Hereditary spherocytosis (HS) is the most common congenital
hemolytic anemia, characterized by anemia, jaundice, and splenomegaly. The
diagnosis of HS relies on symptoms of hemolysis, a family history of HS, and a
positive laboratory test which is usually the osmotic fragility test (OFT). We
conducted a study to assess the utility of mean corpuscular hemoglobin
concentration (MCHC), mean corpuscular volume (MCV), mean sphered cell volume
(MSCV), and mean reticulocyte volume (MRV) in the diagnosis of HS and if these
are helpful in distinguishing cases of HS from immune hemolytic anemia. METHODS:
A total of 102 patients suspected to have HS were enrolled. In addition 10 cases
of immune hemolytic anemia (IHA) were included in the study and performance of
the above screening tests was evaluated. The diagnosis of HS was based on
incubated OFT, eosin 5'-maleimide (EMA) dye binding test, and flowcytometric OFT.
RESULTS: A total of 29 patients were diagnosed as having HS. The sensitivity and
specificity for diagnosis HS by MCHC > 35 g/dL was 44.82%, and DeltaMCV-MSCV > 10
fL has a sensitivity and specificity of 82.75% and 95.9% for diagnosis of HS.
Using an algorithm of DeltaMCV-MSCV > 10 fL and DeltaMRV-MSCV < 25, for the
differentiation of HS from IHA had sensitivity of 68.9% and specificity of 98.8%.
PMID- 29338607
TI - Immunotherapies in transplantation and cancer: 22nd NAT meeting/2nd NAT LabEx IGO
joint meeting; 1-2 June 2017, Nantes, France.
AB - This 22nd edition of the Nantes Actualites Transplantation annual meeting was co
organized for the second time with the LabEx Immuno-Graft Oncology network. This
international meeting was held on 1 and 2 June 2017 in Nantes (western France).
The topic of this 2-day meeting was 'Immunotherapies in transplantation and
cancer'. This meeting brought together 17 international invited speakers, young
researchers and 220 attendees mainly from Europe and North America. It was a
unique opportunity to bring together the pioneers and leading immunologists in
the fields of transplantation and cancer, focusing on shared mechanisms that
control immune responses in organ or bone marrow transplantation and in cancer.
PMID- 29338608
TI - Immunotherapy of cancer: targeting cancer during active disease or during
dormancy?
AB - Immunotherapeutic targeting of advanced stage cancers has prolonged the survival
of cancer patients, yet its curative efficacy is limited due to tumor
immunoediting and escape. On the other hand, human vaccines have been able to
eradicate smallpox and control several other infectious diseases. The success has
resulted from the administration of vaccines in prophylactic settings, or during
latency periods in order to protect an individual during future exposure to the
disease rather than curing an established disease. Therefore, administration of
immunotherapy at the right time is the key to success. However, instead of
focusing on the prevention of cancer, current cancer immunotherapies are often
being used in a therapeutic setting with the goal of eliminating tumor cells. The
present review of evidence related to cancer immunotherapeutics suggests that
immunotherapeutic targeting of tumor dormancy could be more promising than
targeting of advanced stage disease to achieve a cure for cancer.
PMID- 29338609
TI - Chemotherapy-induced immunomodulation in non-small-cell lung cancer: a rationale
for combination chemoimmunotherapy.
AB - Spurred by the survival benefits seen with the use of checkpoint blockade in non
small-cell lung cancer (NSCLC), there has been a growing interest in the
potential applications of immunotherapy. Despite this, the objective response
rate for single-agent immunotherapy remains <=20% in patients with advanced
NSCLC. A combinatorial approach that utilizes both chemotherapy and immunotherapy
is a potential strategy to increase antitumor efficacy. Accumulating evidence has
shown that the immunomodulatory effects of chemotherapeutic agents can be
exploited in a combinational approach. Herein, we review the influence of
specific chemotherapeutic agents on the tumor immune microenvironment in
preclinical and clinical studies, and establish the rationale for combination
chemoimmunotherapy for the treatment of NSCLC.
PMID- 29338611
TI - Hematopoietic and mesenchymal stem cells: a promising new therapy for
spondyloarthritis?
AB - In the last years, a considerable progress has been made in the treatment of
spondyloarthritides. Nonetheless, there remain a considerable number of patients
who are unresponsive to all current therapies. Since the late 1990s, numerous
trials have investigated the use of stem cell transplantation as a new approach
for the treatment of autoimmune disease, particularly with hematopoietic stem
cell transplantation. More recently, the research has focused on mesenchymal stem
cell application due to their low immunogenicity and immunomodulatory properties.
In this article, we summarize available data on hematopoietic stem cell and
mesenchymal stem cell use for the treatment of spondyloarthritides and discuss
the data gaps and possible research agenda in this area.
PMID- 29338610
TI - CNS side effects of immune checkpoint inhibitors: preclinical models, genetics
and multimodality therapy.
AB - Following cancer treatment, patients often report behavioral and cognitive
changes. Novel cancer immunotherapeutics have the potential to produce sustained
cancer survivorship, meaning patients will live longer with the side effects of
treatment. Given the role of inflammatory pathways in mediating behavioral and
cognitive impairments seen in cancer, we aim in this review to discuss emerging
evidence for the contribution of immune checkpoint blockade to exacerbate these
CNS effects. We discuss ongoing studies regarding the ability of immune
checkpoint inhibitors to reach the brain and how treatment responses to
checkpoint inhibitors may be modulated by genetic factors. We further consider
the use of preclinical tumor-models to study the role of tumor status in CNS
effects of immune checkpoint inhibitors and multimodality therapy.
PMID- 29338613
TI - Combined systems of different antibiotics with nano-CuO against Escherichia coli
and the mechanisms involved.
AB - AIM: The combined efficacy of CuO nanoparticles (NPs) with 22 kinds of
antibiotics against Escherichia coli was systematic studied, and CuO with
cephalexin synergistic system was screened out. METHODS: Antimicrobial
susceptibility test included disk diffusion test, checkerboard method and time
kill assay. The interactions of CuO NPs and antibiotics were analyzed by x-ray
photoelectron spectroscopy, Fourier transform infrared spectra and Zeta. The
interactions between bacteria and antibacterial agents were studied by surface
plasmon resonance sensor for the first time. RESULTS & CONCLUSION: Synergistic
effect (1+1>2) was observed when CuO NPs combined with cephalexin against E.
coli. The concentrated cephalexin molecules interacted more strongly with the E.
coli cells to make cell wall become loose. Then, CuO NPs were more easily to
damage and penetrate cells. Besides, the presence of antibiotics did not enhance
Cu2+ release, Cu2+ uptake and reactive oxygen species generation. But the
presence of cephalexin greatly enhanced cell permeability in comparison to
others.
PMID- 29338614
TI - The two mutations of actin-myosin interface and their effect on the dynamics,
structures, and functions of skeletal muscle actin.
AB - Congenital myopathy is a broad category of muscular diseases with symptoms
appearing at the time of birth. One type of congenital myopathy is Congenital
Fiber Type Disproportion (CFTD), a severely debilitating disease. The G48D and
G48C mutations in the D-loop and the actin-myosin interface are the two causes of
CFTD. These mutations have been shown to significantly affect the structure and
function of muscle fibers. To the author's knowledge, the effects of these
mutations have not yet been studied. In this work, the power stroke structure of
the head domain of myosin and the wild and mutated types of actin were modeled.
Then, a MD simulation was run for the modeled structures to study the effects of
these mutations on the structure, function, and molecular dynamics of actin. The
wild and mutated actins docked with myosin showed differences in hydrogen bonding
patterns, free binding energies, and hydrogen bond occupation frequencies. The
G48D and G48C mutations significantly impacted the conformation of D-loops
because of their larger size compared to Glycine and their ability to interfere
with the polarity or hydrophobicity of this neutralized and hydrophobic loop.
Therefore, the mutated loops were unable to fit properly into the hydrophobic
groove of the adjacent G-actin. The abnormal structure of D-loops seems to result
in the abnormal assembly of F-actins, giving rise to the symptoms of CFTD. It was
also noted that G48C and G48D did not form hydrogen bonds with myosin in the
residue 48 location. Nevertheless, in this case, muscles are unable to contract
properly due to muscle atrophy.
PMID- 29338612
TI - Gene Profiling of Nucleus Basalis Tau Containing Neurons in Chronic Traumatic
Encephalopathy: A Chronic Effects of Neurotrauma Consortium Study.
AB - Military personnel and athletes exposed to traumatic brain injury may develop
chronic traumatic encephalopathy (CTE). Brain pathology in CTE includes
intracellular accumulation of abnormally phosphorylated tau proteins (p-tau), the
main constituent of neurofibrillary tangles (NFTs). Recently, we found that
cholinergic basal forebrain (CBF) neurons within the nucleus basalis of Meynert
(nbM), which provide the major cholinergic innervation to the cortex, display an
increased number of NFTs across the pathological stages of CTE. However,
molecular mechanisms underlying nbM neurodegeneration in the context of CTE
pathology remain unknown. Here, we assessed the genetic signature of nbM neurons
containing the p-tau pretangle maker pS422 from CTE subjects who came to autopsy
and received a neuropathological CTE staging assessment (Stages II, III, and IV)
using laser capture microdissection and custom-designed microarray analysis.
Quantitative analysis revealed dysregulation of key genes in several gene
ontology groups between CTE stages. Specifically, downregulation of the nicotinic
cholinergic receptor subunit beta-2 gene (CHRNB2), monoaminergic enzymes catechol
O-methyltransferase (COMT) and dopa decarboxylase (DDC), chloride channels CLCN4
and CLCN5, scaffolding protein caveolin 1 (CAV1), cortical
development/cytoskeleton element lissencephaly 1 (LIS1), and intracellular
signaling cascade member adenylate cyclase 3 (ADCY3) was observed in pS422
immunreactive nbM neurons in CTE patients. By contrast, upregulation of calpain 2
(CAPN2) and microtubule-associated protein 2 (MAP2) transcript levels was found
in Stage IV CTE patients. These single-population data in vulnerable neurons
indicate alterations in gene expression associated with neurotransmission, signal
transduction, the cytoskeleton, cell survival/death signaling, and microtubule
dynamics, suggesting novel molecular pathways to target for drug discovery in
CTE.
PMID- 29338615
TI - Assessment of Canine Mast Cell Tumor Mortality Risk Based on Clinical,
Histologic, Immunohistochemical, and Molecular Features.
AB - Mast cell tumor (MCT) is a frequent cutaneous neoplasm in dogs that is
heterogeneous in clinical presentation and biological behavior, with a variable
potential for recurrence and metastasis. Accurate prediction of clinical outcomes
has been challenging. The study objective was to develop a system for
classification of canine MCT according to the mortality risk based on individual
assessment of clinical, histologic, immunohistochemical, and molecular features.
The study included 149 dogs with a histologic diagnosis of cutaneous or
subcutaneous MCT. By univariate analysis, MCT metastasis and related death was
significantly associated with clinical stage ( P < .0001, rP = -0.610), history
of tumor recurrence ( P < .0001, rP = -0.550), Patnaik ( P < .0001, rP = -0.380)
and Kiupel grades ( P < .0001, rP = -0.500), predominant organization of
neoplastic cells ( P < .0001, rP = -0.452), mitotic count ( P < .0001, rP =
0.325), Ki-67 labeling index ( P < .0001, rP = -0.414), KITr pattern ( P = .02,
rP = 0.207), and c-KIT mutational status ( P < .0001, rP = -0.356). By
multivariate analysis with Cox proportional hazard model, only 2 features were
independent predictors of overall survival: an amendment of the World Health
Organization clinical staging system (hazard ratio [95% CI]: 1.824 [1.210-4.481];
P = .01) and a history of tumor recurrence (hazard ratio [95% CI]: 9.250 [2.158
23.268]; P < .001]. From these results, we propose an amendment of the WHO
staging system, a method of risk analysis, and a suggested approach to clinical
and laboratory evaluation of dogs with cutaneous MCT.
PMID- 29338616
TI - Systemic Loss of C-terminal Src Kinase Expression Elicits Spontaneous Suppurative
Inflammation in Conditional Knockout Mice.
AB - C-terminal Src kinase (Csk) is one of the critical negative regulators of the Src
family of kinases. The Src family of kinases are nonreceptor tyrosine kinases
that regulate inflammation, cell proliferation, motility, and adhesion. To
investigate potential histologic lesions associated with systemic loss of Csk
gene activity in adult mice, conditional Csk-knockout mice were examined. Cre
mediated systemic excision of Csk induced by tamoxifen treatment resulted in
multiorgan inflammation. Specifically, induction of Csk gene excision with three
days of tamoxifen treatment resulted in greater than 90% gene excision.
Strikingly, these mice developed enteritis that ranged from minimal and
suppurative to severe, fibrinonecrosuppurative and hemorrhagic. Other
inflammatory lesions included suppurative pneumonia, gastritis, and myocarditis,
and increased numbers of inflammatory cells within the hepatic parenchyma. When
tamoxifen treatment was reduced from three days to one day in an effort to lower
the level of Csk gene excision and limit lesion development, the mice developed
severe suppurative to pyogranulomatous pneumonia and minimal to mild suppurative
enteritis. Lesions observed secondary to Csk gene excision suggest important
roles for Csk in downregulating the proinflammatory activity of the Src family of
kinases and limiting neutrophil-mediated inflammation.
PMID- 29338617
TI - Carbon nanospheres mediated nuclear delivery of SMAR1 protein (DNA binding
domain) controls breast tumor in mice model.
AB - AIM: To investigate anticancer activity of the DNA binding domain of SMAR1 (His
5) in vitro and in vivo. MATERIALS & METHODS: His 5 was conjugated to
hydrothermally synthesized carbon nanospheres (CNs). Anticancer activity of CNs
His 5 was evaluated in vitro and in vivo. RESULTS: CNs- His 5 significantly
reduced cyclin D1 levels in MDA-MB-231 cells. Tumor bearing Balb/c mice injected
with CNs-His 5 showed approximately 62% tumor regression and significantly
reduced 18FDG uptake. Caspases assay and IHC staining confirmed tumor growth
inhibition, which could be attributed to apoptotic, antiproliferative and
antiangiogenic activities of His 5. CONCLUSION: DNA binding domain of the SMAR1
protein (His 5) has potent anticancer activity and its CNs mediated delivery
could control breast tumor in mice model.
PMID- 29338618
TI - Presence of trauma and suicide risk: Personal control as a moderator.
AB - Given past findings that have linked trauma and lack of personal control to
greater suicidal risk in adults, the present study examined how trauma presence
and personal control are uniquely involved in predicting suicidal risk in a
sample of 469 college students. Regression analyses indicated that both trauma
presence and personal control were significant predictors of suicidal risk, as
was their interaction. The present findings suggest a need to consider both
trauma presence and low personal control in assessing for suicidal risk in
college students.
PMID- 29338619
TI - Novel Phellodendri Cortex (Huang Bo)-derived carbon dots and their hemostatic
effect.
AB - AIM: To explore the hemostatic effect of Phellodendri Cortex-derived carbon dots.
MATERIALS & METHODS: Transmission electron microscopy, high-resolution
transmission electron microscopy, Fourier transform infrared spectroscopy,
ultraviolet-visible spectroscopy, fluorescence spectroscopy, x-ray photoelectron
spectroscopy and a cell counting kit-8 assay were studied. Hemostatic effect of
Phellodendri Cortex Carbonisatus-carbon dots (PCC-CDs) was studied in mouse
bleeding models. To explore their related hemostatic mechanism, coagulation
parameters and platelets were measured. RESULTS: The PCC-CDs ranged in diameter
from 1.2 to 4.8 nm and had a quantum yield of 9.62%. They exhibited no toxicity
up to concentrations of 1000 MUg/ml. After administration, mice had a
significantly shortened bleeding time and coagulation parameters and platelets
significantly increased. CONCLUSION: These results showed the definite hemostatic
effect of PCC-CDs.
PMID- 29338621
TI - Assessing the acute effects of CDP-choline on sensory gating in schizophrenia: A
pilot study.
AB - Deficient sensory gating (SG) in schizophrenia is associated with functional
outcome and offers a therapeutic target as it is linked to the altered
function/expression of the alpha7 nicotinic acetylcholine receptors (nAChRs).
This study analyzed the effects of citicoline (CDP-choline), a supplement with
alpha7 nAChRs agonist properties, on SG in a sample of schizophrenia (SZ)
patients. Using a randomized, placebo-controlled, double-blind design the dose
dependent (500 mg, 1000 mg, 2000 mg) and baseline-dependent (deficient versus
normal suppressors) effects of CDP-choline on SG were examined using the P50
event-related potential (ERP) index of SG. Overall analysis failed to demonstrate
treatment effects but CDP-choline improved SG (500 mg) in the deficient SZ
subgroup by increasing suppression of the S2 P50 amplitude. These findings
tentatively support alpha7 nAChR dysfunction in the expression of SG deficits and
suggest further trials to assess the effects of sustained alpha7 nAChR activation
on SG with low doses of CDP-choline.
PMID- 29338622
TI - Grief and coping of parents whose child has a constant life-threatening
disability, hypoplastic left heart syndrome with reference to the Dual-Process
Model.
AB - This paper reports on a study that examined the grief and coping of 29 parents
whose child has hypoplastic left heart syndrome using the Dual Process Model. The
study employed a secondary thematic analysis of interviews at key times of
treatment and recovery for the child. After the diagnosis, parents experienced
intense loss (LO), but focused upon restoration-orientated tasks (RO) to support
their child. Over time, most parents employed a healthy oscillation between LO
coping and RO coping, with waves of grief and with some grieving suppressed.
There are some specific grief and coping and gender patterns employed by parents.
PMID- 29338620
TI - Diminished Dentate Gyrus Filtering of Cortical Input Leads to Enhanced Area Ca3
Excitability after Mild Traumatic Brain Injury.
AB - Mild traumatic brain injury (mTBI) disrupts hippocampal function and can lead to
long-lasting episodic memory impairments. The encoding of episodic memories
relies on spatial information processing within the hippocampus. As the primary
entry point for spatial information into the hippocampus, the dentate gyrus is
thought to function as a physiological gate, or filter, of afferent excitation
before reaching downstream area Cornu Ammonis (CA3). Although injury has
previously been shown to alter dentate gyrus network excitability, it is unknown
whether mTBI affects dentate gyrus output to area CA3. In this study, we assessed
hippocampal function, specifically the interaction between the dentate gyrus and
CA3, using behavioral and electrophysiological techniques in ex vivo brain slices
1 week following mild lateral fluid percussion injury (LFPI). Behaviorally, LFPI
mice were found to be impaired in an object-place recognition task, indicating
that spatial information processing in the hippocampus is disrupted.
Extracellular recordings and voltage-sensitive dye imaging demonstrated that
perforant path activation leads to the aberrant spread of excitation from the
dentate gyrus into area CA3 along the mossy fiber pathway. These results suggest
that after mTBI, the dentate gyrus has a diminished capacity to regulate cortical
input into the hippocampus, leading to increased CA3 network excitability. The
loss of the dentate filtering efficacy reveals a potential mechanism by which
hippocampal-dependent spatial information processing is disrupted, and may
contribute to memory dysfunction after mTBI.
PMID- 29338623
TI - Diabetic Peripheral Neuropathic Pain From the Perspective of Turkish Patients: A
Qualitative Study.
AB - INTRODUCTION: Diabetic peripheral neuropathy (DPN) affects almost 30% to 50% of
patients with diabetes, 40% to 60% of whom suffer from diabetic peripheral
neuropathic pain (DPNP). Few studies have focused on individual experiences of
DPNP in patients with diabetes. The purpose of this qualitative study was to
elucidate the effects of DPNP on daily life and individual feelings regarding
living with DPNP from the perspective of Turkish patients. METHOD: A total of 14
patients were interviewed, and interpretative phenomenological analysis was used
to identify themes. RESULTS: Findings indicated four main themes, including (a)
physical limitations, (b) difficulties with daily routines, (c) social
limitations, and (d) psychological impacts such as emotional changes, and being a
burden on family. CONCLUSION: This study revealed that the majority of patients
carry significant concerns about becoming a burden on their family and are afraid
of becoming dependent on others because of DPNP. IMPLICATION FOR PRACTICE: For
the effective management of DPNP, health professionals need to consider using a
holistic approach to address difficulties in daily living such as physical
limitations and sexual problems.
PMID- 29338624
TI - Use of Service Learning to Increase Master's-Level Nursing Students'
Understanding of Social Determinants of Health and Health Disparities.
AB - INTRODUCTION: It is important for graduate-level nursing students to be competent
in the issues involved in the social determinants of health and health
disparities and have the tools to address them as graduates. METHOD: As part of a
nursing workforce diversity program, master's-level nursing students were
required to participate in a service learning project exposing them to an issue
not directly linked to health-long bus rides for students as a result of school
consolidations-to achieve educational goals and objectives while providing a
service to an advocacy agency. RESULTS: Eighteen students completed the project,
providing the advocacy agency with firsthand accounts about the impact of long
bus rides and in-depth reviews of literature on the topic and laws and
regulations of other states. CONCLUSION: These results further support providing
nursing students opportunities to fully engage with multicultural communities to
gain a broader understanding of health disparities and social determinants of
health.
PMID- 29338626
TI - Fitts' Law is Applicable to Trunk Coordination Measurements in a Sitting
Position.
AB - Trunk coordination is essential for many activities of daily living in wheelchair
users. This study investigated whether Fitts' law is applicable to trunk
movements in a sitting position. Fourteen healthy adults performed two series of
24 tasks of trunk flexion-extension movements in a sitting position. The results
showed significant linear relationships between average group movement time (MT)
and index of difficulty (ID) over all tasks (r2 = 0.92) and within target
distances (0.94 < r2 < 1.00). Target distance affected intercept and slope (P <
0.001). Hence, Fitts' law is applicable to the studied trunk movements in a
sitting position, indicating these trunk movements tasks could serve as a basis
for qualitative trunk coordination tests. Transferability of these conclusions to
wheelchair users, and optimal test design should be further investigated.
PMID- 29338625
TI - Delivery of chemotherapeutics using spheres made of bioengineered spider silks
derived from MaSp1 and MaSp2 proteins.
AB - AIM: Analysis of the properties and chemotherapeutics delivery potential of
spheres made of bioengineered spider silks MS1 and MS2. MATERIALS & METHODS: MS1
and MS2 derived from Nephila clavipes dragline silks - MaSp1 and MaSp2,
respectively - formed spheres that were compared in terms of physicochemical
properties, cytotoxicity and loading/release of chemotherapeutics. RESULTS: MS2
spheres were more dispersed, smaller, of solid core, of higher beta-sheet
structure content, and of opposite (negative) charge than MS1 spheres. Preloaded
MS2 showed greater applicability for mitoxantrone, while postloaded for etoposide
delivery compared with MS1 spheres. However, MS1 spheres were a better choice for
doxorubicin delivery than MS2. CONCLUSION: Bioengineered silks can be tailored to
develop a system with optimal drug loading and release properties.
PMID- 29338627
TI - ?
PMID- 29338628
TI - ?
PMID- 29338629
TI - [CME Answers: "Lumbar Spinal Canal Stenosis" from PRAXIS No. 01].
PMID- 29338630
TI - [CME: Post-Cardiac Injury Syndrome - a Special Form of Acute Pericarditis.]
PMID- 29338631
TI - ?
PMID- 29338632
TI - ?
PMID- 29338633
TI - ?
PMID- 29338634
TI - ?
PMID- 29338635
TI - ?
PMID- 29338636
TI - ?
PMID- 29338637
TI - Selected plant essential oils and their main active components, a promising
approach to inhibit aflatoxigenic fungi and aflatoxin production in food.
AB - Recent research has showed that Aspergillus flavus and Aspergillus parasiticus
are aflatoxigenic species that can become very competitive in the framework of
climate change. Aflatoxins show carcinogenic, mutagenic, immunotoxic and
teratogenic effects on human and animals. Effective and sustainable measures to
inhibit these species and aflatoxins in food are required. Origanum vulgare and
Cinnamomum zeylanicum essential oils (EOs) and their major active constituents,
carvacrol and cinnamaldehyde, respectively, were assayed for inhibiting these
species and aflatoxin production in maize extract medium under different
environmental conditions. Doses of 10-1000 mg l-1 were assayed and the effective
doses for 50 (ED50) and 90% (ED90) growth inhibition were determined. The ED50 of
cinnamaldehyde, carvacrol, oregano EO, and cinnamon EO against A. flavus were in
the ranges 49-52.6, 98-145, 152-505, 295-560 mg l-1 and against A. parasiticus in
the ranges 46-55.5, 101-175, 260-425 and 490-675 mg l-1, respectively, depending
on environmental conditions. In A. flavus treatments ED90 were in the ranges 89.7
90.5, 770-860 and 820->1000 mg l-1 for cinnamaldehyde, carvacrol and cinnamon EO,
and in A. parasiticus treatments in the ranges 89-91, 855->1000 and 900->1000 mg
l-1, respectively. ED90 values for oregano EO against both species were >1000 mg
l-1. Growth rates of both species were higher at 37 than at 25 degrees C and at
0.99 than at 0.96 aw. Aflatoxin production was higher at 25 than at 37 degrees C.
Stimulation of aflatoxin production was observed at low doses except for
cinnamaldehyde treatments. The effectiveness of EOs and their main constituents
to inhibit fungal growth and aflatoxin production in contact assays was lower
than in vapour phase assays using bioactive EVOH-EO films previously reported.
PMID- 29338638
TI - Frequency-dependence of discomfort caused by vibration and mechanical shocks.
AB - The frequency content of a mechanical shock is not confined to its fundamental
frequency, so it was hypothesised that the frequency-dependence of discomfort
caused by shocks with defined fundamental frequencies will differ from the
frequency-dependence of sinusoidal vibration. Subjects experienced vertical
vibration and vertical shocks with fundamental frequencies from 0.5 to 16 Hz and
magnitudes from +/-0.7 to +/-9.5 ms-2. The rate of growth of discomfort with
increasing magnitude of motion decreased with increasing frequency of both
motions, so the frequency-dependence of discomfort varied with the magnitudes of
both motions and no single frequency weighting will be ideal for all magnitudes.
At the frequencies of sinusoidal vibration producing greatest discomfort (4-16
Hz), shocks produced less discomfort than vibration with same peak acceleration
or unweighted vibration dose value. Frequency-weighted vibration dose values
provided the best predictions of the discomfort caused by different frequencies
and magnitudes of vibration and shock. Practitioner Summary: Human responses to
vibration and shock vary according to the frequency content of the motion. The
ideal frequency weighting depends on the magnitude of the motion. Standardised
frequency-weighted vibration dose values estimate discomfort caused by vibration
and shock but for motions containing very low frequencies the filtering is not
optimum.
PMID- 29338639
TI - Is Continuous Passive Motion Effective in Patients with Lymphedema? A Randomized
Controlled Trial.
AB - BACKGROUND: In this randomized controlled study, we aimed to evaluate the effect
of shoulder flexion exercise using continuous passive motion (CPM) on lymphedema
during the treatment of breast cancer-related lymphedema (BCRL). METHODS: Thirty
patients with BCRL were enrolled and completed the study. Fourteen patients were
treated with complete decongestive therapy (CDT) and CPM in the intervention
group, and 16 patients were treated with CDT alone (control group) for 15
sessions. The main outcome measures were included; the shoulder range of motion
(ROM) assessed with a goniometer, limb volume difference measured using the water
immersion method, function with the Disabilities of the Arm, Shoulder and Hand
(DASH), and the quality of life using the Functional Assessment of Cancer Therapy
for Breast Cancer (FACT-B4). Lymphedema volume measures were taken at baseline,
on days 1, 2, 3, 4, 5, 10, and 15; and shoulder ROM, FACT-B4, and DASH were taken
at baseline and on day 15. RESULTS: All subjects were similar at baseline. After
treatment significant improvement was found in ROM, volumetric differences, DASH,
and FACT-B4 scores in both groups. No significant differences were observed in
the volumetric differences, ROM, and the DASH, and FACT-B4 scores between the
groups, except for the FACT-B4 physical well-being subscores, which were better
in intervention group. CONCLUSION: Our study results showed that CPM did not
contribute to the reduction of BCRL.
PMID- 29338640
TI - New molecular features of cowpea bean (Vigna unguiculata, l. Walp) beta-vignin.
AB - Cowpea seed beta-vignin, a vicilin-like globulin, proved to exert various health
favourable effects, including blood cholesterol reduction in animal models. The
need of a simple scalable enrichment procedure for further studies for tailored
applications of this seed protein is crucial. A chromatography-independent
fractionation method allowing to obtain a protein preparation with a high degree
of homogeneity was used. Further purification was pursued to deep the molecular
characterisation of beta-vignin. The results showed: (i) differing glycosylation
patterns of the two constituent polypeptides, in agreement with amino acid
sequence features; (ii) the seed accumulation of a gene product never identified
before; (iii) metal binding capacity of native protein, a property observed only
in few other legume seed vicilins.
PMID- 29338641
TI - An assessment of the level of awareness and reported complaints regarding
occupational health hazards and the utilization of personal protective equipments
among the welders of Lahore, Pakistan.
AB - Objective To assess the level of awareness and reported complaints of
occupational health hazards among the welders of Lahore. Methods A cross
sectional descriptive study of 70 welders. An interview questionnaire was
employed to assess awareness and complaints, the possession and utilization of
protective personal equipment (PPE), and socio-demographic characteristics.
Results All of the respondents were male with a mean age of 25.7 years. 54.3% of
the respondents were aware of welding as a risk to their health. 98.6% possessed
at least 1 PPE. There was an association between the level of education and the
awareness of a health risk (chi2 = 6.885; p = 0.032). The most frequent complaint
was foreign body in the eye (47.1%) followed by arc eye injury (45.7%), cuts and
injuries (50.0%), and burns (48.6%). Conclusion The findings suggest that welders
had low level of awareness and reported many complaints of occupational health
hazards. Preventive initiatives are recommended.
PMID- 29338642
TI - Functional evolution of biosynthetic enzymes that produce plant volatiles.
AB - Plants synthesize volatile compounds to attract pollinators. The volatiles
emitted by flowers are often complex mixtures of organic compounds; pollinators
are capable of distinctly recognizing different volatile compounds. Plants also
produce volatile compounds to protect themselves against herbivores and
pathogens. Some of the volatile compounds produced in floral and vegetative
tissues are toxic to insects and microbes. To adapt changes in the environment,
plants have evolved the ability to synthesize a unique set of volatiles.
Intensive studies have identified and characterized the enzymes responsible for
the formation of plant volatiles. In particular, many biosynthetic genes have
been isolated and their enzymatic functions have been proposed. This review
describes how plants have evolved the biosynthetic pathways leading to the
formation of green leaf volatiles and phenylpropene volatiles.
PMID- 29338643
TI - High School Coaches' Experiences With Openly Lesbian, Gay, and Bisexual Athletes.
AB - Despite reports that there has been a positive trend in perception and treatment
of lesbian, gay, and bisexual (LGB) individuals in recent years (Griffin, 2012 ;
Loftus, 2001 ), sport, in general, is still an uncertain, and sometimes even
hostile, environment for LGB athletes (Anderson, 2005 ; Waldron & Krane, 2005 ).
To gain more information on coach understanding and perceptions of the team
environment, 10 high school head coaches in the United States were interviewed to
explore their experiences coaching openly LGB athletes. Qualitative analyses
revealed four primary themes associated with coach experiences: team environment
dogmas and observations, fundamental beliefs contributing to perceptions of LGB
athletes, types and timing of sexual orientation disclosure, and differential LGB
athlete characteristics. Future research should examine these primary themes in
more detail through interviews with LGB athletes, as well as high school coaches
in more traditionally masculine sports, such as football, men's basketball, and
wrestling.
PMID- 29338644
TI - Pulmonary mucoepidermoid carcinoma: diagnosis and treatment.
AB - INTRODUCTION: Primary mucoepidermoid carcinomas (MEC) of the lung are rare and
represent a diagnostic challenge. MEC in the lung is under the umbrella of
primary salivary gland type tumors of the lung. Areas covered: In general,
salivary gland type tumors are represented by malignant neoplasms that may range
from low to intermediate to high-grade type of malignancy sharing similar
histopathological features as those in salivary glands. The focus in this review
will be on one tumor in particular - mucoepidermoid carcinoma. Clinical,
radiological, histopathological, and molecular diagnostic features will be
highlighted in order to provide an insight on this unusual tumor in the lung. In
addition, the treatment of these tumors will be discussed. Expert commentary: It
is important to stress that in the majority of cases, the proper use of
histopathological assessment is the most important step in arriving at an
accurate diagnosis. It is also important to recognized that there are other
unusual primary tumoral conditions of the lung, which may pose a significant
challenge in the differential diagnosis. The importance of proper recognition of
mucoepidermoid carcinoma and its grading will be highlighted in order to assess
clinical outcome.
PMID- 29338645
TI - Remote Iliac Artery Endarterectomy: A Case Series and Systematic Review.
AB - PURPOSE: To evaluate the long-term results of remote iliac artery endarterectomy
(RIAE) in 2 vascular referral centers and review existing literature. METHODS: A
retrospective analysis was conducted of 109 consecutive patients (mean age 64.2+/
10.7 years; 72 men) who underwent 113 RIAE procedures for lower limb ischemia
from January 2004 to August 2015 at 2 vascular centers. The majority of limbs
(82, 72.6%) had TASC II D lesions (31 TASC II C). Primary outcome measures were
primary, assisted primary, and secondary patency. A comprehensive literature
search was performed in the PubMed and EMBASE databases to identify all English
language studies published after 1990 reporting the results of RIAE. RESULTS:
Technical success was achieved in 95 (84.1%) of the 113 procedures. The
complication rate was 13.7%, and 30-day mortality was 0%. At 5 years, primary
patency was 78.2%, assisted primary patency was 83.4%, and secondary patency was
86.7%. Hemodynamic success was obtained in 91.7% of patients, and clinical
improvement was observed in 95.2%. Freedom from major amputation was 94.7% at 5
years. The systematic review comprised 6 studies including 419 RIAEs, and pooled
data showed results similar to the current study. CONCLUSION: For external iliac
artery occlusions extending into the common femoral artery, RIAE appears to be a
valuable hybrid treatment option. It combines acceptable morbidity and low
mortality with good long-term patency. It has some advantages over an open
surgical iliofemoral bypass or complete endovascular revascularization and could
be the best treatment option in selected cases.
PMID- 29338646
TI - Cognitive determinants of cervical cancer screening behavior among housewife
women in Iran: An application of Health Belief Model.
AB - Our aim in this cross-sectional study was to assess the cognitive determinants of
Cervical Cancer Screening Behavior (CCSB) among housewife women in Islamabad
County, Iran. Through multistage random sampling we recruited and interviewed 280
housewife women. The women who perceived more benefits of performing the Pap test
(OR = 1.11), and perceived fewer barriers (OR = 0.915), and higher self-efficacy
to perform the test (OR = 1.12) were more likely to have a CCSB in the previous
three years. Our findings are informative for the development of targeted
interventions to foster CCSB among housewife women.
PMID- 29338650
TI - Stoicism and Alchemy in Late Antiquity: Zosimus and the Concept of Pneuma.
AB - At the beginning of the twentieth century, historians associated the alchemy of
the third-century alchemist Zosimus of Panopolis with Platonism and
Aristotelianism, explicating his theory of alchemical transmutation under the
intellectual umbrella of these philosophical traditions. More recently, scholars
of alchemy such as Christina Viano and William Newman have suggested a connection
between Zosimean alchemy and Stoicism. Through a close reading of texts in
Zosimus's corpus, this paper posits a Stoic interpretation of several aspects of
Zosimean alchemy, focusing on the concepts of pneuma and tension. For Zosimus, I
argue, pneuma played a vital role in colouring metals, while tension conferred
stability and cohesion upon metallic compounds. This interpretation suggests that
Zosimus applied Stoic concepts to describe the alchemical process of tincturing
metals.
PMID- 29338653
TI - A New Alchemical Poem Attributed to Khalid b. Yazid (d. ca. 705).
AB - This paper deals primarily with the identification of an inaccurately catalogued
alchemical poem attributed to the famous Umayyad prince Khalid b. Yazid (d. 705),
edited, translated, and commented upon here for the first time. The paper also
addresses the authenticity of Khalid's interest in alchemy and connects that
interest to the need of the early Islamic empire to develop its own gold coinage
as a sign of political independence from Byzantine coinage that was up till then
the currency of the lands occupied by early Muslims in the regions of modern-day
Egypt and Syria. On the matter of the legendry character of Khalid which was
apparently started by Ibn Khaldun and passed on after him to most nineteenth
century and early twentieth-century orientalists, the paper exposes here the
inner contradictions in Ibn Khaldun's theorising on the matter, and his failure
to understand why someone like the historical Prince Khalid would be interested
in alchemy.
PMID- 29338655
TI - The Alchemical Manuscripts of David Lindsay (1587-1641), Lord Lindsay of
Balcarres.
AB - The private book collection of David Lindsay, First Lord Lindsay of Balcarres
(1587-1641), was one of the largest in early modern Scotland. Despite being
dispersed during the following three centuries, this collection still provides
evidence for Lindsay's scientific interests and approach to the study of alchemy.
In this paper we seek to partially reconstruct his library by describing and,
where possible, identifying the sources of Lindsay's own transcriptions of
alchemical texts, as well as works mentioned in a book-list written in his hand.
We conclude that Lindsay was not just an important early modern collector, but
also a careful reader, part of an extensive network of contacts with whom he
exchanged books and information.
PMID- 29338658
TI - The Chemical Club: An Early Nineteenth-Century Scientific Dining Club.
AB - The Chemical Club (fl. 1806-1828) was a small scientific dining club in London.
Among its members were Sir Humphry Davy, William Hyde Wollaston, and Alexander
Marcet. Other accomplished men of science, including John Dalton, Jons Jacob
Berzelius, and Augustin Pyramus de Candolle, also attended its meetings as
guests. This article, drawing on the unpublished papers of Lionel Felix Gilbert,
as well as a range of contemporary sources in print and manuscript, presents the
first substantial history of the Chemical Club, and situates it in the context of
the scientific and social networks of the period. It aims to enrich our
understanding of the scientific culture of the early nineteenth century in
Britain by tracing the Club's influence on, or connection to, some of the most
pioneering and transformative scientific work of the first quarter of the 1800s,
such as the discovery of nitrogen trichloride, the invention of the miners'
safety lamp, and Hans Christian Orsted's work on electromagnetism.
PMID- 29338659
TI - Enfranchising grief following suicide: A case study of an Israeli social
organization.
AB - Researchers have yet to explore suicide survivors activities in social
organizations, which was the present purpose. I studied an Israeli organization,
Path to Life, by interviewing 16 members, attending 11 events, and examining
media, online, and print information. Although mainly comprised of activists
whose loss occurred in civilian circumstances, frame analysis revealed that the
organization emphasizes connections between suicide and esteemed military-related
death. By relying on a legitimate model of dealing with death, the activists
provided meaning to suicide and promoted a sociocultural change through drawing
attention to a silenced death, upgrading the suicide victims' status, and
enfranchising survivors' grief.
PMID- 29338661
TI - Collaborative Processes of Developing A Health Literacy Toolkit: A Case from
Fukushima after the Nuclear Accident.
AB - Following the Fukushima nuclear accident in 2011, the central government provided
health and radiation-related information that was incomplete, difficult to
understand and contradictory, leading to widespread distrust in the community.
Thus, from 2013 to 2014, we developed and implemented a series of health literacy
training workshops for local public health nurses, often the first health care
professionals with whom members of the community interact. The results from our
program evaluation revealed that the task of paraphrasing professional terms and
skills related to relaying numeric information to the community were difficult
for the nurses to acquire. In 2016, to further support the communication efforts
of public health nurses, we developed a pocket-size "health literacy toolkit"
that contained a glossary explaining radiation-related terms in plain language
and an index to measure the accessibility of both text and numerical information,
so that nurses could calibrate and appreciate the literacy demand of information.
This case study documents an interprofessional collaborative effort for the
development of the toolkit, and highlights the iterative process of building
health literacy skills in health care professionals.
PMID- 29338660
TI - Social-ecological factors associated with selling sex among men who have sex with
men in Jamaica: results from a cross-sectional tablet-based survey.
AB - BACKGROUND: Globally, men who have sex with men (MSM) experience social
marginalization and criminalization that increase HIV vulnerability by
constraining access to HIV prevention and care. People who sell sex also
experience criminalization, rights violations, and violence, which elevate HIV
exposure. MSM who sell sex may experience intersectional stigma and intensified
social marginalization, yet have largely been overlooked in epidemiological and
social HIV research. In Jamaica, where same sex practices and sex work are
criminalized, scant research has investigated sex selling among MSM, including
associations with HIV vulnerability. OBJECTIVE: We aimed to examine social
ecological factors associated with selling sex among MSM in Jamaica, including
exchanging sex for money, shelter, food, transportation, or drugs/alcohol (past
12 months). METHODS: We conducted a cross-sectional survey with a peer-driven
sample of MSM in Kingston, Ocho Rios, and Montego Bay. Multivariable logistic
regression analyses were conducted to estimate intrapersonal/individual,
interpersonal/social, and structural factors associated with selling sex.
RESULTS: Among 556 MSM, one-third (n = 182; 32.7%) reported selling sex. In the
final multivariable model, correlates of selling sex included:
individual/intrapersonal (lower safer sex self-efficacy [AOR: 0.85, 95% CI: 0.77,
0.94]), interpersonal/social (concurrent partnerships [AOR: 5.52, 95% CI: 1.56,
19.53], a higher need for social support [AOR: 1.08, 95% CI: 1.03, 1.12],
lifetime forced sex [AOR: 2.74, 95% 1.65, 4.55]) and structural-level factors
(sexual stigma [AOR: 1.09, 95% CI: 1.04, 1.15], food insecurity [AOR: 2.38, 95%
CI: 1.41, 4.02], housing insecurity [AOR: 1.94, 95% CI: 1.16, 3.26], no regular
healthcare provider [AOR: 2.72, 95% CI: 1.60, 4.64]). CONCLUSIONS: This study
highlights social ecological correlates of selling sex among MSM in Jamaica, in
particular elevated stigma and economic insecurity. Findings suggest that MSM in
Jamaica who sell sex experience intensified social and structural HIV
vulnerabilities that should be addressed in multi-level interventions to promote
health and human rights.
PMID- 29338662
TI - Legal barriers to access abortion services through a human rights lens: the
Uruguayan experience.
AB - Sexual and reproductive health (SRH) has increasingly gained importance in the
field of international human rights law. The work of the United Nations (UN)
bodies, in particular the recently adopted General Comment 22 (GC 22), has been
instrumental in signalling the importance of the SRH legal framework and in
setting clear guidelines to steer countries into enacting/modifying/repealing
national laws in order to comply with their international obligations vis-a-vis
SRH. Although within the region Uruguay is regarded as a pioneer in terms of
women's status and rights, including sexual and reproductive health and rights,
evidence points to a number of challenges. This article explores the extent to
which the Uruguayan abortion law complies with the country's international human
rights obligations as conceptualised by GC 22. It uses the Uruguayan abortion
law, its regulatory decree, and the highest administrative court's decision in
Alonso et al v. Poder Ejecutivo as the main pivots for the discussion. The
results reveal that - in spite of the praise it receives at the international
level and the adoption of a less restrictive abortion law - Uruguay has fallen
short in adopting a legal framework that complies with the international
standards and guarantees effective access to abortion services.
PMID- 29338663
TI - Cultural Competency in Dementia Care: An African American Case Study.
AB - Age is the greatest risk factor for Alzheimer's disease, the most common cause of
dementia. The older population in the United States is growing, and within this
demographic ethnic and racial diversity is also on the rise. This article
introduces Stanford Health Care's Memory Support Program (MSP) as a model for
culturally competent dementia care that spans inpatient and outpatient settings.
The case study of an African American patient and family dealing with an
Alzheimer's disease diagnosis and comorbid conditions is presented and explored
to illustrate the MSP model. The authors make recommendations for the
implementation of similar continuum of care services in other institutions. As
research continues to show, the cultural competence of medical professionals can
impact patient quality of care and health outcomes. More research is needed to
appropriately support positive outcomes for patients and families of diverse
ethnic and racial backgrounds.
PMID- 29338664
TI - Qualitative analysis and conceptual mapping of patient experiences in home health
care.
AB - This study explored patient experiences in home health care through a literature
review, focus groups, and interviews. Our goal was to develop a conceptual map of
home health care patient experience domains. The conceptual map identifies
technical and personal spheres of care, relating prior studies to new focus group
and interview findings and identifying the most important domains of care. Study
participants (n = 35) most frequently reported the most important domain as staff
who are caring, supportive, patient, empathetic, respectful, and considerate
(endorsed by 29% of participants). The conceptual map includes 114 discrete
domains.
PMID- 29338665
TI - Adjuvant radiotherapy in patients with diffuse large B-cell lymphoma in advanced
stage (III/IV) improves the outcome in the rituximab era.
AB - OBJECTIVES: To assess the efficacy and toxicity of adjuvant radiotherapy (RT) in
patients with diffuse large B-cell lymphoma (DLBCL) and nodal bulky disease, on
complete response, after six cycles of RCHOP (rituximab, cyclophosphamide,
doxorubicin, vincristine and prednisone), we began an open-label clinical trial
in a large cohort with longer follow-up to evaluate the outcome measured from
progression-free survival (PFS) and overall survival (OS). PATIENTS AND METHODS:
Between 2006 and 2010, 258 consecutive patients with DLBCL and nodal bulky
disease (tumor mass >10 cm) were randomly assigned to receive either RT (involved
field, 30 Gy) (127 patients) or no (control group) (131 patients). RESULTS: The
actuarial curves at 5 years of PFS were 87% (95% confidence interval (CI): 72
97%) in the RT group, which was significantly different from the control group
value of 45% (95% CI: 34-60%) (p < 0.001); also OS in the RT group was
significantly better than that in the control group: 91% (95% CI: 84-99%) and 59%
(95% CI: 52-66%), respectively (p < 0.001). RT was well tolerated, acute toxicity
was mild and until now late toxicity did not appear. CONCLUSIONS: The use of
adjuvant RT in patients with DLBCL and nodal bulky disease improves the outcome
with PFS and OS, with minimal toxicity; thus, we felt that adjuvant RT will be
considered as a part of the initial treatment in this setting of patients, even
in the rituximab era.
PMID- 29338667
TI - Docosahexaenoic acid prevents resistance to antiepileptic drugs in two animal
models of drug-resistant epilepsy.
AB - OBJECTIVES: One-third of epileptic patients are resistant to antiepileptic drugs.
Few clinical studies with small sample size indicate that polyunsaturated fatty
acids could control drug-resistant epilepsy. We examined the efficacy of acute
and chronic administration of docosahexaenoic acid (DHA) in two animal models of
drug-resistant epilepsies, i.e. 6-Hz psychomotor seizures in mice and lamotrigine
(LTG)-resistant kindled rats. METHODS: Mice received a single injection of DHA
(300 uM, i.c.v.) along with phenytoin (PHT) or LTG (i.p.). Six-Hz electroshock
(0.2 milliseconds rectangular pulse width, 3 seconds duration, 44 mA current) was
given 15 minutes after DHA, and seizure behaviors were recorded. In LTG-resistant
kindled rats, a single dose of DHA (300 uM, i.c.v.) was administered with LTG,
and seizure parameters were measured. In chronic treatment, mice received DHA
(0.1 g/day, orally) for 30 days. Then, a single dose of LTG or PHT was
administered to mice and 6-Hz-induced seizures were recorded. In rats, DHA (1 uM,
i.c.v.) was administered during kindling development and effect of LTG in DHA
pretreated LTG-resistant kindled rats was verified. RESULTS: LTG and PHT did not
inhibit 6-Hz seizures in mice after single injection of DHA. However, LTG and PHT
inhibited 6-Hz seizures in mice that received DHA for 1 month. Acute or chronic
administration of DHA to LTG-resistant kindled rats led to the suppression of
kindled seizure parameters by LTG. DISCUSSION: DHA removes the 'inherent
resistance' of 6-Hz seizures to PHT and LTG, and prevents the development of
pharmacodynamic tolerance to LTG in LTG-resistant kindled rats. DHA might have
potential to be used as add-on therapy in patients with refractory epilepsy.
PMID- 29338666
TI - Boosted TCA cycle enhances survival of zebrafish to Vibrio alginolyticus
infection.
AB - Vibrio alginolyticus is a waterborne pathogen that infects a wide variety of
hosts including fish and human, and the outbreak of this pathogen can cause a
huge economic loss in aquaculture. Thus, enhancing host's capability to survive
from V. alginolyticus infection is key to fighting infection and this remains
still unexplored. In the present study, we established a V. alginolyticus
zebrafish interaction model by which we explored how zebrafish survived from V.
alginolyticus infection. We used GC-MS based metabolomic approaches to
characterize differential metabolomes between survival and dying zebrafish upon
infection. Pattern recognition analysis identified the TCA cycle as the most
impacted pathway. The metabolites in the TCA cycle were decreased in the dying
host, whereas the metabolites were increased in the survival host. Furthermore,
the enzymatic activities of the TCA cycle including pyruvate dehydrogenase (PDH),
alpha-ketoglutaric dehydrogenase (KGDH) and succinate dehydrogenase (SDH) also
supported this conclusion. Among the increased metabolites in the TCA cycle,
malic acid was the most crucial biomarker for fish survival. Indeed, exogenous
malate promoted zebrafish survival in a dose-dependent manner. The corresponding
activities of KGDH and SDH were also increased. These results indicate that the
TCA cycle is a key pathway responsible for the survival or death in response to
infection caused by V. alginolyticus, and highlight the way on development of
metabolic modulation to control the infection.
PMID- 29338668
TI - Simultaneous determination of afidopyropen and its metabolite in vegetables,
fruit and soil using UHPLC-MS/MS.
AB - A new analytical method using the quick, easy, cheap, effective, rugged and safe
(QuEChERS) procedure for simultaneous determination of afidopyropen and its
metabolite M440I007 residues in tomato, watermelon, pepper, cucumber, pear,
grape, cabbage and soil samples was developed using ultra-high performance liquid
chromatography coupled with tandem mass spectrometry. The target compound was
determined in less than 5.0 min using an electrospray ionisation source in
positive mode (ESI+). The limit of quantification was 1 MUg kg-1 in different
matrices. Two sorbents primary secondary amine and graphitised carbon black were
used in the QuEChERS procedure, and matrix-matched standards gave satisfactory
recoveries and relative standard deviation (RSD) values in different matrices at
three spiked levels (1, 10 and 500 MUg kg-1). For afidopyropen, the recoveries
ranged from 83% to 104% with an intra-day relative standard deviation (RSDr) of 1
8%, while they were from 80% to 103% with RSDr of 2-8% for M440I007.
Reproducibility ranged between 1% and 19% for the three spiked levels.
PMID- 29338669
TI - Successful operative treatment of uterine leiomyoma with extensive intravenous
extension to the IVC, right heart, and pulmonary arteries.
AB - INTRODUCTION: Intravenous extension of benign uterine leiomyomata ('fibroids'),
in the absence of discrete metastatic disease has rarely been reported.
'Fibroids' remain one of the most common premenopausal uterine pathologies.
METHODS AND RESULTS: We report the diagnosis and multidisciplinary led operative
management of a 52-year-old woman with a histologically benign, but biologically
aggressive, uterine leiomyoma with intravenous extension to the inferior vena
cava (IVC), right heart and pulmonary arteries. CONCLUSIONS: Total abdominal
hysterectomy and bilateral salpingo-oophorectomy combined with exploration of the
sub-hepatic IVC and heart under deep hypothermic circulatory arrest achieved its
successful macroscopic clearance.
PMID- 29338670
TI - Vitamin A and vitamin D deficiencies exacerbate symptoms in children with autism
spectrum disorders.
AB - OBJECTIVES: This study was designed to investigate the vitamin A (VA) and vitamin
D (VD) levels in children with autism spectrum disorders (ASD) and to determine
whether co-deficiency of VA and VD exacerbates clinical symptoms in autistic
children. METHODS: The Autism Behavior Checklist, Childhood Autism Rating Scale
(CARS), and Social Responsiveness Scale (SRS) were used to assess the symptoms of
332 children diagnosed as ASD. And the Gesell Developmental Scale (GDS) was used
to evaluate neurodevelopment in children with ASD. Anthropometric measurement and
questionnaire results were compared for all autistic children and 197 age- and
gender-matched control children. Serum retinol levels were detected with high
performance liquid chromatography, and serum levels of 25-OH vitamin D were
measured with an immunoassay method in the two groups. RESULTS: The ZHA, ZWA, and
ZBMIA of the children with ASD were significantly lower than those of the control
children. Furthermore, higher proportions of children with picky eating,
resistance to new foods, and eating problems were observed in the ASD group when
compared with the control group. Serum retinol and 25-OH vitamin D levels in
autistic children were significantly lower than those in the control children.
Additionally, VA and VD co-deficiency impacts more on the symptoms and
development in autistic children. CONCLUSIONS: We found that children with autism
have more VA and VD deficiencies than control children, and VA and VD co
deficiency may exacerbate the symptoms of children with ASD.
PMID- 29338671
TI - Journal of Correctional Health Care.
PMID- 29338673
TI - Editor's Letter.
PMID- 29338674
TI - Would you be willing to zap your child's brain? Public perspectives on parental
responsibilities and the ethics of enhancing children with transcranial direct
current stimulation.
AB - BACKGROUND: Transcranial direct current stimulation (tDCS) is an experimental
brain stimulation technology that may one day be used to enhance the cognitive
capacities of children. Discussion about the ethical issues that this would raise
has rarely moved beyond expert circles. However, the opinions of the wider public
can lead to more democratic policy decisions and broaden academic discussion of
this issue. METHODS: We performed a quantitative survey of members of the U.S.
public. A between-subjects design was employed, where conditions varied based on
the trait respondents considered for enhancement. RESULTS: There were 227
responses included for analysis. Our key finding was that the majority were
unwilling to enhance their child with tDCS. Respondents were most reluctant to
enhance traits considered fundamental to the self (such as motivation and
empathy). However, many respondents may give in to implicit coercion to enhance
their child in spite of an initial reluctance. A ban on tDCS was not supported if
it were to be used safely for the enhancement of mood or mathematical ability.
Opposition to such a ban may be related to the belief that tDCS use would not
represent cheating or violate authenticity (as it relates to achievements rather
than identity). CONCLUSIONS: The wider public appears to think that crossing the
line from treatment to enhancement with tDCS would not be in a child's best
interests. However, an important alternative interpretation of our results is
that lay people may be willing to use enhancers that matched their preference for
"natural" enhancers. A ban on the safe use of tDCS for enhancing nonfundamental
traits would be unlikely to garner public support. Nonetheless, it could become
important to regulate tDCS in order to prevent misuse on children, because
individuals reluctant to enhance may be likely to give in to implicit coercion to
enhance their child.
PMID- 29338675
TI - Exploration into best practices in peer support for bereaved survivors.
AB - This exploratory, qualitative study addresses the question: what are the
important elements in effective peer support programs for bereaved survivors?
Interviews with 10 highly experienced experts were analyzed to identify recurrent
themes and elements. Findings indicate that effective peer support programs for
the bereaved should be: easily accessible; confidential; provide a safe
environment; use peer supporters with similar shared experiences to clients;
select peer supporters carefully; partner with professional mental health
providers; train peer supporters thoroughly; and provide care and monitoring for
peer supporters. These results can help inform efforts to improve peer support
programs for bereaved survivors.
PMID- 29338676
TI - Finding the perfect sclerosant - Is it possible?
PMID- 29338677
TI - Vitamin B-6 and depressive symptomatology, over time, in older Latino adults.
AB - BACKGROUND: Low vitamin B-6 status has been linked to depressive symptomatology.
We examined the longitudinal association of vitamin B-6 status with depressive
symptomatology across 3-time points over ~5-7 years in a cohort of older Hispanic
adults. METHODS: We used two-level hierarchical linear regression models for
continuous outcomes. Vitamin B-6 status was associated with depressive
symptomatology across these time points. RESULTS: Plasma pyridoxyl-5-phosphate
(PLP) concentration, a time-varying predictor, was significantly associated with
depressive symptomatology. Study participants with PLP deficiency, vs. optimal
PLP, had higher baseline depressive symptoms (Center for Epidemiologic Studies
Depression Scale (CES-D) score of 22 +/- 14, vs. 20 +/- 13); this differential
remained constant over time and persisted after controlling for age, sex,
education, body mass index, smoking and alcohol use, other relevant nutritional
factors, perceived stress, stressful life events, allostatic load, and use of
antidepressant medication. However, PLP concentration was not associated with the
rate of change in depressive symptomatology over time. CONCLUSIONS: Suboptimal
plasma PLP is associated with higher depressive symptomatology in older Hispanic
of Puerto Rican descent and this appears to persist over time. Our data suggest
that identification and treatment of vitamin B-6 deficiency may be a useful
preventive approach in this population.
PMID- 29338678
TI - Supplementation with Curcuma longa reverses neurotoxic and behavioral damage in
models of Alzheimer's disease: A systematic review.
AB - BACKGROUND: The formation of senile plaques and neurofibrillary tangles of the
tau protein are the main pathological mechanism of Alzheimer's disease (AD).
Current therapies for AD offer discrete benefits to the clinical symptoms and do
not prevent the continuing degeneration of neuronal cells. Therefore, novel
therapeutic strategies have long been investigated, where curcumin (Curcuma
longa) has shown some properties that can prevent the deleterious processes
involved in neurodegenerative diseases. OBJECTIVE: The aim of the present work is
to review studies that addressed the effects of curcumin in experimental models
(in vivo and in vitro) for AD. METHOD: This study is a systematic review
conducted between January and June 2017, in which a consultation of scientific
articles from indexed periodicals was carried out in Science Direct, United
States National Library of Medicine (PubMed), Cochrane Library and Scielo
databases, using the following descriptors: "Curcuma longa", "Curcumin" and
"Alzheimer's disease". RESULTS: A total of 32 studies were analyzed, which
indicated that curcumin supplementation reverses neurotoxic and behavioral
damages in both in vivo and in vitro models of AD. CONCLUSION: The administration
of curcumin in experimental models seems to be a promising approach in AD, even
though it is suggested that additional studies must be conducted using distinct
doses and through other routes of administration.
PMID- 29338679
TI - Therapeutic role of methotrexate in pediatric Crohn's disease.
AB - The main role of therapy in Crohn's disease (CD) is to achieve long-term clinical
remission, and to allow for normal growth and development of children. The
immunomodulatory drugs used for the maintenance of remission in CD include
thiopurines (azathioprine and 6-mercaptopurine) and methotrexate (MTX).
Development of hepatosplenic T-cell lymphoma in some patients with inflammatory
bowel disease, treated with thiopurines only or in combination with anti-tumor
necrosis factor agents, resulted in a growing interest in the therapeutic
application of MTX in children suffering from CD. This review summarizes the
literature on the therapeutic role of MTX in children with CD. MTX is often
administered as a second-line immunomodulator, and 1-year clinical remission was
reported in 25-69% of children with CD after excluding for the use of
thiopurines. Initial data on MTX effectiveness in mucosal healing, and as a first
line immunomodulator in pediatric patients with CD, are promising. A definite
conclusion, however, may only be made on the basis of additional research with a
larger number of subjects.
PMID- 29338680
TI - MicroRNA-466 (miR-466) functions as a tumor suppressor and prognostic factor in
colorectal cancer (CRC).
AB - MicroRNAs (miRNAs) have an important role in the regulation of tumor development
and metastasis. In this study, we investigated the clinical and prognostic value
as well as biological function of miR-466 in colorectal cancer (CRC). Tumor and
adjacent healthy tissues were obtained from 100 patients diagnosed with CRC. miR
466 expression was determined by quantitative reverse transcription polymerase
chain reaction (qRT-PCR). mRNA and protein levels of cyclin D1, apoptosis
regulator BAX (BAX), and matrix metalloproteinase-2 (MMP-2) were analyzed by qRT
PCR and Western blot, respectively, in SW-620 CRC cells transfected with miR-466
mimics or negative control miRNA. Effects of miR-466 on SW-620 cell
proliferation, cell cycle and apoptosis, and invasion were investigated using CCK
8 assay, flow cytometry and Transwell assay, respectively. miR-466 expression was
significantly downregulated in tumor tissues compared to matched adjacent non
tumor tissues. Low expression of miR-466 was significantly correlated with the
tumor size, Tumor Node Metastasis stage, lymph node metastasis, and distant
metastasis. The overall survival of CRC patients with low miR-466 expression was
significantly shorter compared to high-miR-466 expression group (log-rank test: p
= 0.0103). Multivariate analysis revealed that low miR-466 expression was
associated with poor prognosis in CRC patients. The ectopic expression of miR-466
suppressed cell proliferation and migration/invasion, as well as induced G0/G1
arrest and apoptosis in SW-620 cells. Moreover, the ectopic expression of miR-466
decreased the expression of cyclin D1 and MMP-2, but increased BAX expression in
SW-620 cells. In conclusion, our findings demonstrated that miR-466 functions as
a suppressor miRNA in CRC and may be used as a prognostic factor in these
patients.
PMID- 29338681
TI - The evolutionary process of mammalian sex determination genes focusing on
marsupial SRYs.
AB - BACKGROUND: Maleness in mammals is genetically determined by the Y chromosome. On
the Y chromosome SRY is known as the mammalian male-determining gene. Both
placental mammals (Eutheria) and marsupial mammals (Metatheria) have SRY genes.
However, only eutherian SRY genes have been empirically examined by functional
analyses, and the involvement of marsupial SRY in male gonad development remains
speculative. RESULTS: In order to demonstrate that the marsupial SRY gene is
similar to the eutherian SRY gene in function, we first examined the sequence
differences between marsupial and eutherian SRY genes. Then, using a parsimony
method, we identify 7 marsupial-specific ancestral substitutions, 13 eutherian
specific ancestral substitutions, and 4 substitutions that occurred at the stem
lineage of therian SRY genes. A literature search and molecular dynamics
computational simulations support that the lineage-specific ancestral
substitutions might be involved with the functional differentiation between
marsupial and eutherian SRY genes. To address the function of the marsupial SRY
gene in male determination, we performed luciferase assays on the testis enhancer
of Sox9 core (TESCO) using the marsupial SRY. The functional assay shows that
marsupial SRY gene can weakly up-regulate the luciferase expression via TESCO.
CONCLUSIONS: Despite the sequence differences between the marsupial and eutherian
SRY genes, our functional assay indicates that the marsupial SRY gene regulates
SOX9 as a transcription factor in a similar way to the eutherian SRY gene. Our
results suggest that SRY genes obtained the function of male determination in the
common ancestor of Theria (placental mammals and marsupials). This suggests that
the marsupial SRY gene has a function in male determination, but additional
experiments are needed to be conclusive.
PMID- 29338682
TI - Soybean MADS-box gene GmAGL1 promotes flowering via the photoperiod pathway.
AB - BACKGROUND: The MADS-box transcription factors are an ancient family of genes
that regulate numerous physiological and biochemical processes in plants and
facilitate the development of floral organs. However, the functions of most of
these transcription factors in soybean remain unknown. RESULTS: In this work, a
MADS-box gene, GmAGL1, was overexpressed in soybean. Phenotypic analysis showed
that GmAGL1 overexpression not only resulted in early maturation but also
promoted flowering and affected petal development. Furthermore, the GmAGL1 was
much more effective at promoting flowering under long-day conditions than under
short-day conditions. Transcriptome sequencing analysis showed that before
flowering, the photoperiod pathway photoreceptor CRY2 and several circadian
rhythm genes, such as SPA1, were significantly down-regulated, while some other
flowering-promoting circadian genes, such as GI and LHY, and downstream genes
related to flower development, such as FT, LEAFY, SEP1, SEP3, FUL, and AP1, were
up-regulated compared with the control. Other genes related to the flowering
pathway were not noticeably affected. CONCLUSIONS: The findings reported herein
indicate that GmAGL1 may promote flowering mainly through the photoperiod
pathway. Interestingly, while overexpression of GmAGL1 promoted plant maturity,
no reduction in seed production or oil and protein contents was observed.
PMID- 29338684
TI - A simple prediction model to estimate obstructive coronary artery disease.
AB - BACKGROUND: A simple noninvasive model to predict obstructive coronary artery
disease (OCAD) may promote risk stratification and reduce the burden of coronary
artery disease (CAD). This study aimed to develop pre-procedural, noninvasive
prediction models that better estimate the probability of OCAD among patients
with suspected CAD undergoing elective coronary angiography (CAG). METHODS: We
included 1262 patients, who had reliable Framingham risk variable data, in a
cohort without known CAD from a prospective registry of patients referred for
elective CAG. We investigated pre-procedural OCAD (>=50% stenosis in at least one
major coronary vessel based on CAG) predictors. RESULTS: A total of 945 (74.9%)
participants had OCAD. The final modified Framingham scoring (MFS) model
consisted of anemia, high-sensitivity C-reactive protein, left ventricular
ejection fraction, and five Framingham factors (age, sex, total and high-density
lipoprotein cholesterol, and hypertension). Bootstrap method (1000 times)
revealed that the model demonstrated a good discriminative power (c statistic,
0.729 +/- 0.0225; 95% CI, 0.69-0.77). MFS provided adequate goodness of fit (P =
0.43) and showed better performance than Framingham score (c statistic, 0.703 vs.
0.521; P < 0.001) in predicting OCAD, thereby identifying patients with high
risks for OCAD (risk score >= 27) with >=70% predictive value in 68.8% of
subjects (range, 37.2-87.3% for low [<=17] and very high [>=41] risk scores).
CONCLUSION: Our data suggested that the simple MFS risk stratification tool,
which is available in most primary-level clinics, showed good performance in
estimating the probability of OCAD in relatively stable patients with suspected
CAD; nevertheless, further validation is needed.
PMID- 29338685
TI - Functional health state description and valuation by people aged 65 and over: a
pilot study.
AB - BACKGROUND: Assessing quality of life among the elderly is a complex and
multifaceted issue. Elderly people might find valuing and describing their
personal experience of quality of life (QoL) demanding and cumbersome. This study
therefore sought to determine the feasibility of administering two questionnaires
in two samples of elderly people. METHODS: A preference-based instrument (EQ-5D +
C) and a currently achieved functioning questionnaire (CAF) were utilized. Two
pilot studies were performed. The first was performed in South Africa (n = 30),
designed to test whether elderly respondents could complete and understand the
two questionnaires and also to indicate which valuation method, visual analogue
scale or time trade off they preferred. A second pilot study was performed in the
Netherlands (n = 30), designed to investigate the use of both questionnaires in
determining quality of life and health state valuations in a Dutch sample of
elderly. RESULTS: Seventy percent of the South African respondents indicated that
they preferred the visual analogue scale (VAS) method, when compared to the time
trade-off (TTO). In both the South African and the Dutch pilot studies, the
respondents, with different dependency levels, were able to use both
questionnaires to determine health state descriptions and valuations. When
ranking the profiles from fewer to more problems, the EQ-5D + C exhibits a
gradual downwards trend, with a maximum of 100 and minimum VAS value of 41. The
CAF also exhibits a gradual downwards trend, with a maximum of 1.00 and minimum
VAS value of 36. CONCLUSIONS: The results indicate that individuals from
different parts of the world are able to complete, describe, and value the
questionnaires. It is our recommendation that a comprehensive study should be
done, which includes both the EQ-5D + C questionnaire and the CAF questionnaire,
since the two questionnaires have proven to be feasible in providing information
on quality of life and well-being of elderly people.
PMID- 29338683
TI - Genomic repeats, misassembly and reannotation: a case study with long-read
resequencing of Porphyromonas gingivalis reference strains.
AB - BACKGROUND: Without knowledge of their genomic sequences, it is impossible to
make functional models of the bacteria that make up human and animal microbiota.
Unfortunately, the vast majority of publicly available genomes are only working
drafts, an incompleteness that causes numerous problems and constitutes a major
obstacle to genotypic and phenotypic interpretation. In this work, we began with
an example from the class Bacteroidia in the phylum Bacteroidetes, which is
preponderant among human orodigestive microbiota. We successfully identify the
genetic loci responsible for assembly breaks and misassemblies and demonstrate
the importance and usefulness of long-read sequencing and curated reannotation.
RESULTS: We showed that the fragmentation in Bacteroidia draft genomes assembled
from massively parallel sequencing linearly correlates with genomic repeats of
the same or greater size than the reads. We also demonstrated that some of these
repeats, especially the long ones, correspond to misassembled loci in three
reference Porphyromonas gingivalis genomes marked as circularized (thus complete
or finished). We prove that even at modest coverage (30X), long-read resequencing
together with PCR contiguity verification (rrn operons and an integrative and
conjugative element or ICE) can be used to identify and correct the wrongly
combined or assembled regions. Finally, although time-consuming and labor
intensive, consistent manual biocuration of three P. gingivalis strains allowed
us to compare and correct the existing genomic annotations, resulting in a more
accurate interpretation of the genomic differences among these strains.
CONCLUSIONS: In this study, we demonstrate the usefulness and importance of long
read sequencing in verifying published genomes (even when complete) and
generating assemblies for new bacterial strains/species with high genomic
plasticity. We also show that when combined with biological validation processes
and diligent biocurated annotation, this strategy helps reduce the propagation of
errors in shared databases, thus limiting false conclusions based on incomplete
or misleading information.
PMID- 29338686
TI - Correction to: Effectiveness and safety of vitamin K antagonists and new
anticoagulants in the prevention of thromboembolism in atrial fibrillation in
older adults - a systematic review of reviews and the development of
recommendations to reduce inappropriate prescribing.
AB - CORRECTION: After publication of the original article [1] it was found that
author Marc Krause's name had been spelt incorrectly. In the original article it
is presented as Mark Krause, rather than Marc Krause. The revised spelling has
been included in the author list for this Correction.
PMID- 29338687
TI - Use of easy measurable phenotypic traits as a complementary approach to evaluate
the population structure and diversity in a high heterozygous panel of tetraploid
clones and cultivars.
AB - BACKGROUND: Diversity in crops is fundamental for plant breeding efforts. An
accurate assessment of genetic diversity, using molecular markers, such as single
nucleotide polymorphism (SNP), must be able to reveal the structure of the
population under study. A characterization of population structure using easy
measurable phenotypic traits could be a preliminary and low-cost approach to
elucidate the genetic structure of a population. A potato population of 183
genotypes was evaluated using 4859 high-quality SNPs and 19 phenotypic traits
commonly recorded in potato breeding programs. A Bayesian approach, Minimum
Spanning Tree (MST) and diversity estimator, as well as multivariate analysis
based on phenotypic traits, were adopted to assess the population structure.
RESULTS: Analysis based on molecular markers showed groups linked to the
phylogenetic relationship among the germplasm as well as the link with the
breeding program that provided the material. Diversity estimators consistently
structured the population according to a priori group estimation. The phenotypic
traits only discriminated main groups with contrasting characteristics, as
different subspecies, ploidy level or membership in a breeding program, but were
not able to discriminate within groups. A joint molecular and phenotypic
characterization analysis discriminated groups based on phenotypic
classification, taxonomic category, provenance source of genotypes and genetic
background. CONCLUSIONS: This paper shows the significant level of diversity
existing in a parental population of potato as well as the putative phylogenetic
relationships among the genotypes. The use of easily measurable phenotypic traits
among highly contrasting genotypes could be a reasonable approach to estimate
population structure in the initial phases of a potato breeding program.
PMID- 29338688
TI - Transurethral resection of the prostate provides more favorable clinical outcomes
compared with conservative medical treatment in patients with urinary retention
caused by benign prostatic obstruction.
AB - BACKGROUND: To evaluate the long-term surgical outcomes of patients with urinary
retention (UR) caused by a benign prostatic obstruction (BPO) who underwent
transurethral resection of the prostate (TURP), and compare their outcomes with
those of patients who received medication without surgical intervention. METHODS:
This retrospective cohort study analyzed claims data collected during the period
of 1997-2012 from Taiwan's National Health Insurance Research Database. We
examined geriatric adverse events among patients who had received a diagnosis of
symptomatic benign prostatic hyperplasia and whom experienced UR, and compared
those who received TURP and medication only. Primary outcomes included urinary
tract infection (UTI), UR, inguinal hernia, hemorrhoids, stroke, acute myocardial
infarction, and bony fracture. We excluded patients who had concomitant prostate
cancer, bladder cancer, or a long-term urinary catheter indwelling, as well as
those who did not receive alpha-blocker medication regularly. Those aged <50 or
>90 years were also excluded. The enrolled patients were categorized into TURP (n
= 1218) and medication only (n = 795) groups. After 1:1 propensity score
matching, we recorded and compared patients' characteristics, postoperative
clinical outcomes, and geriatric adverse events. RESULTS: The TURP cohort had a
lower incidence of UTI and UR during the postoperative follow-up period from 2
months to 3 years than did the medication only group (20.7% vs. 28.9% and 12.5%
vs. 27.6%, respectively, p < 0.001). The life-long bone fracture incidence was
also lower in the TURP cohort (7.9% vs. 9.2%, p = 0.048). The incidence of other
outcomes during the postoperative follow-up period did not differ between the two
groups. CONCLUSIONS: Compared with conservative treatment, TURP provides more
favorable clinical outcomes in patients with UR caused by BPO. Patients who
underwent TURP had a lower risk of UTI, repeat UR episodes, and emergent bony
fracture. Thus, early surgical intervention should be considered for such
patients.
PMID- 29338690
TI - Multimorbidity patterns in the elderly: a prospective cohort study with cluster
analysis.
AB - BACKGROUND: Multimorbidity is the coexistence of more than two chronic diseases
in the same individual; however, there is no consensus about the best definition.
In addition, few studies have described the variability of multimorbidity
patterns over time. The aim of this study was to identify multimorbidity patterns
and their variability over a 6-year period in patients older than 65 years
attended in primary health care. METHODS: A cohort study with yearly cross
sectional analysis of electronic health records from 50 primary health care
centres in Barcelona. Selected patients had multimorbidity and were 65 years of
age or older in 2009. Diagnoses (International Classification of Primary Care,
second edition) were extracted using O'Halloran criteria for chronic diseases.
Multimorbidity patterns were identified using two steps: 1) multiple
correspondence analysis and 2) k-means clustering. Analysis was stratified by sex
and age group (65-79 and >=80 years) at the beginning of the study period.
RESULTS: Analysis of 2009 electronic health records from 190,108 patients with
multimorbidity (59.8% women) found a mean age of 71.8 for the 65-79 age group and
84.16 years for those over 80 (Standard Deviation [SD] 4.35 and 3.46,
respectively); the median number of chronic diseases was seven (Interquartil
range [IQR] 5-10). We obtained 6 clusters of multimorbidity patterns (1
nonspecific and 5 specifics) in each group, being the specific ones:
Musculoskeletal, Endocrine-metabolic, Digestive/Digestive-respiratory,
Neurological, and Cardiovascular patterns. A minimum of 42.5% of the sample
remained in the same pattern at the end of the study, reflecting the stability of
these patterns. CONCLUSIONS: This study identified six multimorbidity patterns
per each group, one nonnspecific pattern and five of them with a specific pattern
related to an organic system. The multimorbidity patterns obtained had similar
characteristics throughout the study period. These data are useful to improve
clinical management of each specific subgroup of patients showing a particular
multimorbidity pattern.
PMID- 29338689
TI - Variants of cancer susceptibility genes in Korean BRCA1/2 mutation-negative
patients with high risk for hereditary breast cancer.
AB - BACKGROUND: We evaluated the incidence and spectrum of pathogenic and likely
pathogenic variants of cancer susceptibility genes in BRCA1/2 mutation-negative
Korean patients with a high risk for hereditary breast cancer using a
comprehensive multigene panel that included 35 cancer susceptibility genes.
METHODS: Samples from 120 patients who were negative for BRCA1/2 mutations, but
had been diagnosed with breast cancer that was likely hereditary, were
prospectively evaluated for the prevalence of high-penetrance and moderate
penetrance germline mutations. RESULTS: Nine patients (7.5%) had at least one
pathogenic or likely pathogenic variant. Ten variants were identified in these
patients: TP53 in two patients, PALB2 in three patients, BARD1 in two patients,
BRIP1 in two patients, and MRE11A in one patient. We also identified 30 types of
139 variants of unknown significance (VUS). High-penetrance germline mutations,
including TP53 and PALB2, tended to occur with high frequency in young (< 35
years) breast cancer patients (4/19, 21.1%) than in those diagnosed with breast
cancer at >=35 years of age (1/101, 1.0%; p = 0.003). CONCLUSIONS: These combined
results demonstrate that multigene panels offer an alternative strategy for
identifying veiled pathogenic and likely pathogenic mutations in breast cancer
susceptibility genes.
PMID- 29338691
TI - mORCA: ubiquitous access to life science web services.
AB - BACKGROUND: Technical advances in mobile devices such as smartphones and tablets
have produced an extraordinary increase in their use around the world and have
become part of our daily lives. The possibility of carrying these devices in a
pocket, particularly mobile phones, has enabled ubiquitous access to Internet
resources. Furthermore, in the life sciences world there has been a vast
proliferation of data types and services that finish as Web Services. This
suggests the need for research into mobile clients to deal with life sciences
applications for effective usage and exploitation. RESULTS: Analysing the current
features in existing bioinformatics applications managing Web Services, we have
devised, implemented, and deployed an easy-to-use web-based lightweight mobile
client. This client is able to browse, select, compose parameters, invoke, and
monitor the execution of Web Services stored in catalogues or central
repositories. The client is also able to deal with huge amounts of data between
external storage mounts. In addition, we also present a validation use case,
which illustrates the usage of the application while executing, monitoring, and
exploring the results of a registered workflow. The software its available in the
Apple Store and Android Market and the source code is publicly available in
Github. CONCLUSIONS: Mobile devices are becoming increasingly important in the
scientific world due to their strong potential impact on scientific applications.
Bioinformatics should not fall behind this trend. We present an original software
client that deals with the intrinsic limitations of such devices and propose
different guidelines to provide location-independent access to computational
resources in bioinformatics and biomedicine. Its modular design makes it easily
expandable with the inclusion of new repositories, tools, types of visualization,
etc.
PMID- 29338692
TI - Emerging roles for microRNA in the regulation of Drosophila circadian clock.
AB - BACKGROUND: The circadian clock, which operates within an approximately 24-h
period, is closely linked to the survival and fitness of almost all living
organisms. The circadian clock is generated through a negative transcription
translation feedback loop. microRNAs (miRNAs) are small non-coding RNAs comprised
of approximately 22 nucleotides that post-transcriptionally regulate target mRNA
by either inducing mRNA degradation or inhibiting translation. RESULTS: In recent
years, miRNAs have been found to play important roles in the regulation of the
circadian clock, especially in Drosophila. In this review, we will use fruit
flies as an example, and summarize the progress achieved in the study of miRNA
mediated clock regulation. Three main aspects of the circadian clock, namely, the
free-running period, locomotion phase, and circadian amplitude, are discussed in
detail in the context of how miRNAs are involved in these regulations. In
addition, approaches regarding the discovery of circadian-related miRNAs and
their targets are also discussed. CONCLUSIONS: Research in the last decade
suggests that miRNA-mediated post-transcriptional regulation is crucial to the
generation and maintenance of a robust circadian clock in animals. In flies,
miRNAs are known to modulate circadian rhythmicity and the free-running period,
as well as circadian outputs. Further characterization of miRNAs, especially in
the circadian input, will be a vital step toward a more comprehensive
understanding of the functions underlying miRNA-control of the circadian clock.
PMID- 29338693
TI - In vitro antimicrobial susceptibility testing of human Brucella melitensis
isolates from Ulanqab of Inner Mongolia, China.
AB - BACKGROUND: Brucellosis is an endemic disease in the Inner Mongolia Autonomous
Region of China and Ulanqab exhibits the highest prevalence of brucellosis in
this region. Due to the complex nature of Brucellosis, a cure for this disease
has proven to be elusive. Furthermore, the reduced susceptibility of Brucella
spp. to antimicrobial agents has been reported as a potential cause of
therapeutic failure. However, detailed in vitro antimicrobial susceptibility
patterns pertaining to Brucella isolates from this region have not yet been
published. The aim of this study was to evaluate the antibiotic susceptibility
profile of Brucella melitensis clinical isolates from Ulanqab, Inner Mongolia,
China. METHODS: A total of 85 B. melitesis isolates were obtained from humans in
Ulanqab of Inner Mongolia, China; the antimicrobial susceptibility of 85 clinical
isolates to nine antibiotics was assessed using the E-test method according to
the CLSI (Clinical and Laboratory Standards Institute) guidelines. RESULTS: All
of the tested isolates were susceptible to minocycline, sparfloxacin,
doxycycline, tetracycline, ciprofloxacin, gentamicin and levofloxacin. Resistance
to rifampin and cotrimoxazole was observed in 1.0% (1/85) and 7.0% (6/85) of the
isolates, respectively. However, rpoB gene mutations were not observed in single
isolates exhibiting resistance to rifampin. CONCLUSIONS: We observed that B.
melitensis isolates are susceptible to the majority of the tested antibiotics.
Furthermore, minocycline and sparfloxacin exhibited extremely high bactericidal
effects in relation to the B. melitensis isolates. The sensitivity of commonly
used drugs for the treatment of brucellosis should be regularly monitored. To the
best of our knowledge, this is the first report of rifampin and cotrimoxazole
resistant isolates of B. melitensis in China. In summary, based on the findings
from this study, we suggest that antibiotic administration and use should be
rationalized to prevent future drug resistance.
PMID- 29338694
TI - Development of a physical literacy model for older adults - a consensus process
by the collaborative working group on physical literacy for older Canadians.
AB - BACKGROUND: Arguably the uptake and usability of the physical activity (PA)
guidelines for older adults has not been effective with only 12% of this
population meeting the minimum guidelines to maintain health. Health promoters
must consider innovative ways to increase PA adoption and long-term
sustainability. Physical literacy (PL) is emerging as a promising strategy to
increase lifelong PA participation in younger age-groups, yet there is relatively
little evidence of PL being used to support older adults in achieving the PA
guidelines. METHODS: An iterative and mixed-methods consensus development process
was utilized over a series of six informed processes and meetings to develop a
model of physical literacy for adults aged 65 years and older. RESULTS: A multi
disciplinary collaborative working group (n = 9) from diverse practice settings
across Canada, and representative and reflective of the full range of key
elements of PL, was assembled. Three consensus meetings and two Delphi surveys,
using an international cohort of 65 expert researchers, practitioners, non
government organizations and older adults, was conducted. 45% responded on the
first round and consensus was achieved; however, we elected to run a second
survey to support our results. With 79% response rate, there was consensus to
support the new PL model for older adults. CONCLUSION: Older adults are a unique
group who have yet to be exposed to PL as a means to promote long-term PA
participation. This new PL model uses an ecological approach to integrate PL into
the lifestyles of most older adults. Understanding the interactions between
components and elements that facilitate PL will ultimately provide a new and
effective tool to target PA promotion and adherence for all older Canadians.
PMID- 29338695
TI - Novel sensing technology in fall risk assessment in older adults: a systematic
review.
AB - BACKGROUND: Falls are a major health problem for older adults with significant
physical and psychological consequences. A first step of successful fall
prevention is to identify those at risk of falling. Recent advancement in sensing
technology offers the possibility of objective, low-cost and easy-to-implement
fall risk assessment. The objective of this systematic review is to assess the
current state of sensing technology on providing objective fall risk assessment
in older adults. METHODS: A systematic review was conducted in accordance to the
Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement
(PRISMA). RESULTS: Twenty-two studies out of 855 articles were systematically
identified and included in this review. Pertinent methodological features
(sensing technique, assessment activities, outcome variables, and fall
discrimination/prediction models) were extracted from each article. Four major
sensing technologies (inertial sensors, video/depth camera, pressure sensing
platform and laser sensing) were reported to provide accurate fall risk
diagnostic in older adults. Steady state walking, static/dynamic balance, and
functional mobility were used as the assessment activity. A diverse range of
diagnostic accuracy across studies (47.9% - 100%) were reported, due to variation
in measured kinematic/kinetic parameters and modelling techniques. CONCLUSIONS: A
wide range of sensor technologies have been utilized in fall risk assessment in
older adults. Overall, these devices have the potential to provide an accurate,
inexpensive, and easy-to-implement fall risk assessment. However, the variation
in measured parameters, assessment tools, sensor sites, movement tasks, and
modelling techniques, precludes a firm conclusion on their ability to predict
future falls. Future work is needed to determine a clinical meaningful and easy
to interpret fall risk diagnosis utilizing sensing technology. Additionally, the
gap between functional evaluation and user experience to technology should be
addressed.
PMID- 29338697
TI - Additional dexamethasone in chemotherapies with carboplatin and paclitaxel could
reduce the impaired glycometabolism in rat models.
AB - BACKGROUND: Side-effects have been considered as the limitation of the
chemotherapy agents' administration and life quality in patients with ovarian
cancers. In order to explore the influence of the chemotherapy agents commonly
used in ovarian cancer patients on the blood glucose metabolism in rat models, we
conducted this study which simulated the conditions of clinical protocols.
METHODS: Eighty clean-grade female Wistar rats were randomized into 8 groups:
Group 1 (Negative control), Group 1' (Dexamethasone), Group 2 (Carboplatin),
Group 2' (Carboplatin-plus-dexamethasone), Group 3 (Paclitaxel), Group 3'
(Paclitaxel-plus-dexamethasone), Group 4 (Combined therapy), Group 4' (Combined
therapy-plus-dexamethasone). On day 0, 4, 7 and 14, after fasted for 12 h, the
rats in all groups underwent a glucose load and their blood glucose, glucagon and
insulin levels were measured. RESULTS: The glucose levels in group 2, 3 and 4 at
1 h after the loading on day 4 significantly increased (P = 0.190, 0.008 and
0.025, respectively). The glucagon levels in group 3 and 4 showed a similar trend
and the increase was not suppressed by the glucose loading (P < 0.001). A
significant decrease of insulin levels in group 2, 3 and 4 were observed on day
14 after treatment (P = 0.043, 0.019 and 0.019, respectively). The change of
HOMA2 %B, an index reflects the ability of insulin secretion was negatively
corresponded to the glucose levels, and the trends of HOMA2 IR, an index shows
insulin resistance, were positively correlated to the glucose levels. The
application of dexamethasone could reduce the degree of increased glucose levels
significantly in group 2, 3 and 4. There were no differences in overall survival
between the 8 groups. Edema in the stroma of pancreases was observed in group 3,
3', 4 and 4' on day 4 after treatment (P = 0.002, 0.002, 0.000 and 0.000
respectively) and lasted until day 14. CONCLUSIONS: Carboplatin and paclitaxel
administration could cause a transient hyperglycemia in rats. This effect might
occur by the combination of glucagon accumulation due to the decrease in islet
cell secretion. The additional dexamethasone in the combination protocol of
carboplatin and paclitaxel seemed to reduce the impaired blood glucose
metabolism.
PMID- 29338698
TI - Enteral immunonutrition versus enteral nutrition for gastric cancer patients
undergoing a total gastrectomy: a systematic review and meta-analysis.
AB - BACKGROUND: Nutrition support is a common means for patients with gastric cancer,
especially for those undergoing elective surgery. Recently, enteral
immunonutrition (EIN) was increasingly found to be more effective than enteral
nutrition (EN) in enhancing the host immunity and eventually improving the
prognosis of gastric cancer patients undergoing gastrectomy. However, the results
reported were not consistent. This meta-analysis aimed to assess the impact of
EIN for patients with GC on biochemical, immune indices and clinical outcomes.
METHODS: Four electronical databases (Medline, EMBASE, Scopus and Cochrane
library) were used to search articles in peer-reviewed, English-language
journals. Mean difference (MD), Relative risk (RR), or standard mean difference
(SMD) with 95% confidence interval (CI) were calculated. Heterogeneity was
assessed by Cochrane Q and I2 statistic combined with corresponding P-value. The
analysis was carried out with RevMan 5.3. RESULTS: Seven studies involving 583
patients were eligible for the pooled analysis. EIN, when beyond a 7-day time
frame post-operatively (D >= 7), increased level of CD4+ (SMD = 0.99; 95% CI,
0.65-1.33; P < 0.00001), CD4+/ CD8+ (SMD = 0.34; 95% CI, 0.02-0.67; P = 0.04),
the IgM (SMD = 1.15; 95% CI, 0.11-2.20; P = 0.03), the IgG (SMD = 0.98; 95% CI,
0.55-1.42; P < 0.0001), the lymphocyte (SMD = 0.69; 95% CI, 0.32-1.06; P =
0.0003), and the proalbumin (SMD = 0.73; 95% CI, 0.33-1.14; P = 0.0004). However,
those increased effects were not obvious within a 7-day time-frame post
operatively (D < 7). The levels of CD8+ and other serum proteins except
proalbumin were not improved both on D >= 7 and D < 7. Clinical outcomes such as
systemic inflammatory response syndrone (SIRS) (MD, - 0.89 days; 95% CI, - 1.40
to - 0.39; P = 0.005), and postoperative complications (RR, 0.29; 95% CI, 0.14
0.60; P = 0.001) were significantly reduced in EIN group. Pulmonary infection and
length of hospitalization (LHS) were not improved no matter what time after
surgery. CONCLUSIONS: EIN was found to improve the cellular immunity, modulate
inflammatory reaction and reduce postoperative complication for GC patients
undergoing radical gastrointestinal surgery. Exclusion of grey literature and non
English language studies was the key limitation in this study.
PMID- 29338699
TI - Assessing predictors of intention to prescribe sick leave among primary care
physicians using the theory of planned behaviour.
AB - BACKGROUND: Providing sickness certification is a decision that primary care
physicians make on a daily basis. The majority of sickness certification studies
in the literature involve a general assessment of physician or patient behaviour
without the use of a robust psychological framework to guide research accuracy.
To address this deficiency, this study utilized the Theory of Planned Behaviour
(TPB) to specifically gauge the intention and other salient predictors related to
sickness certification prescribing behaviour amongst primary care physicians.
METHODS: A cross-sectional study was conducted among N = 271 primary care
physicians from 86 primary care practices throughout two states in Malaysia.
Questionnaires used were specifically developed based on the TPB, consisting of
both direct and indirect measures related to the provision of sickness leave.
Questionnaire validity was established through factor analysis and the
determination of internal consistency between theoretically related constructs.
The temporal stability of the indirect measures was determined via the test
retest correlation analysis. Structural equation modelling was conducted to
determine the strength of predictors related to intentions. RESULTS: The mean
scores for intention to provide patients with sickness was low. The Cronbach
alpha value for the direct measures was good: overall physician intent to provide
sick leave (0.77), physician attitude towards prescribing sick leave for patients
(0.77) and physician attitude in trusting the intention of patients seeking sick
leave (0.83). The temporal stability of the indirect measures of the
questionnaire was satisfactory with significant correlation between constructs
separated by an interval of two weeks (p < 0.05). Attitudes and subjective norms
were identified as important predictors in physician intention to provide sick
leave to patients. CONCLUSION: An integrated behavioural model utilizing the TPB
could help fully explain the complex act of providing sickness leave to patients.
Findings from this study could assist relevant agencies to facilitate the
creation of policies that may help regulate the provision of sickness leave and
alleviate the work burden of sickness leave tasks faced by physicians in
Malaysia.
PMID- 29338696
TI - Transcriptional responses of Escherichia coli during recovery from inorganic or
organic mercury exposure.
AB - BACKGROUND: The protean chemical properties of mercury have long made it
attractive for diverse applications, but its toxicity requires great care in its
use, disposal, and recycling. Mercury occurs in multiple chemical forms, and the
molecular basis for the distinct toxicity of its various forms is only partly
understood. Global transcriptomics applied over time can reveal how a cell
recognizes a toxicant and what cellular subsystems it marshals to repair and
recover from the damage. The longitudinal effects on the transcriptome of
exponential phase E. coli were compared during sub-acute exposure to mercuric
chloride (HgCl2) or to phenylmercuric acetate (PMA) using RNA-Seq. RESULTS:
Differential gene expression revealed common and distinct responses to the
mercurials throughout recovery. Cultures exhibited growth stasis immediately
after each mercurial exposure but returned to normal growth more quickly after
PMA exposure than after HgCl2 exposure. Correspondingly, PMA rapidly elicited up
regulation of a large number of genes which continued for 30 min, whereas fewer
genes were up-regulated early after HgCl2 exposure only some of which overlapped
with PMA up-regulated genes. By 60 min gene expression in PMA-exposed cells was
almost indistinguishable from unexposed cells, but HgCl2 exposed cells still had
many differentially expressed genes. Relative expression of energy production and
most metabolite uptake pathways declined with both compounds, but nearly all
stress response systems were up-regulated by one or the other mercurial during
recovery. CONCLUSIONS: Sub-acute exposure influenced expression of ~45% of all
genes with many distinct responses for each compound, reflecting differential
biochemical damage by each mercurial and the corresponding resources available
for repair. This study is the first global, high-resolution view of the
transcriptional responses to any common toxicant in a prokaryotic model system
from exposure to recovery of active growth. The responses provoked by these two
mercurials in this model bacterium also provide insights about how higher
organisms may respond to these ubiquitous metal toxicants.
PMID- 29338700
TI - Correction to: A systematic comparison of copy number alterations in four types
of female cancer.
AB - After publication of the original article [1] the authors found that the article
contained an incorrect version of Fig. 4. This does not affect the results and
conclusions of the article.
PMID- 29338701
TI - SSH1 expression is associated with gastric cancer progression and predicts a poor
prognosis.
AB - BACKGROUND: Slingshot homolog-1 (SSH1) plays an important role in pathological
processes, including in the occurrence and development of tumours. The purpose of
this study was to determine whether SSH1 is a key biomarker with prognostic value
for survival in patients with gastric cancer. METHODS: We performed
immunohistochemistry (IHC) on tissue microarrays containing 100 gastric cancer
specimens to evaluate SSH1 protein expression. The association of pathological
characteristics with cumulative survival was determined by Kaplan-Meier analysis.
A Cox proportional hazards model was generated in the multi-factorial survival
analysis to identify univariate prognostic factors of GC. RESULTS: SSH1
expression level in gastric cancer tissues was significantly associated with
lymph node metastasis (P = 0.032). Additionally, multivariate regression analysis
clearly indicated that SSH1 expression was significantly correlated with poor
clinical outcomes of patients with gastric cancer (P = 0.016). Multivariate
analyses showed that SSH1 was the best predictor of poor prognosis in patients
with gastric cancer (P = 0.030). CONCLUSIONS: SSH1 expression is associated with
gastric cancer progression and predicts a poor prognosis. SSH1 may play an
important role in the development of gastric cancer, and it is a promising target
for prevention and/or treatment of gastric cancer.
PMID- 29338702
TI - Estimating the scale of chronic hepatitis C virus infection in the EU/EEA: a
focus on migrants from anti-HCV endemic countries.
AB - BACKGROUND: Increasing the proportion diagnosed with and on treatment for chronic
hepatitis C (CHC) is key to the elimination of hepatitis C in Europe. This study
contributes to secondary prevention planning in the European Union/European
Economic Area (EU/EEA) by estimating the number of CHC (anti-HCV positive and
viraemic) cases among migrants living in the EU/EEA and born in endemic
countries, defining the most affected migrant populations, and assessing whether
country of birth prevalence is a reliable proxy for migrant prevalence. METHODS:
Migrant country of birth and population size extracted from statistical databases
and anti-HCV prevalence in countries of birth and in EU/EEA countries derived
from a systematic literature search were used to estimate caseload among and most
affected migrants. Reliability of country of birth prevalence as a proxy for
migrant prevalence was assessed via a systematic literature search. RESULTS:
Approximately 11% of the EU/EEA adult population is foreign-born, 79% of whom
were born in endemic (anti-HCV prevalence >=1%) countries. Anti-HCV/CHC
prevalence in migrants from endemic countries residing in the EU/EEA is estimated
at 2.3%/1.6%, corresponding to ~580,000 CHC infections or 14% of the CHC disease
burden in the EU/EEA. The highest number of cases is found among migrants from
Romania and Russia (50-60,000 cases each) and migrants from Italy, Morocco,
Pakistan, Poland and Ukraine (25-35,000 cases each). Ten studies reporting
prevalence in migrants in Europe were identified; in seven of these estimates,
prevalence was comparable with the country of birth prevalence and in three
estimates it was lower. DISCUSSION: Migrants are disproportionately affected by
CHC, account for a considerable number of CHC infections in EU/EEA countries, and
are an important population for targeted case finding and treatment. Limited data
suggest that country of birth prevalence can be used as a proxy for the
prevalence in migrants.
PMID- 29338703
TI - Diagnostic accuracy and prediction increment of markers of epithelial-mesenchymal
transition to assess cancer cell detachment from primary tumors.
AB - BACKGROUND: Metastases play a role in about 90% of cancer deaths. Markers of
epithelial-mesenchymal transition (EMT) measured in primary tumor cancer cells
might provide diagnostic information about the likelihood that cancer cells have
detached from the primary tumor. Used together with established diagnostic tests
of detachment-lymph node evaluation and radiologic imaging-EMT marker
measurements might improve the ability of clinicians to assess the patient's risk
of metastatic disease. Translation of EMT markers to clinical use has been
hampered by a lack of valid analyses of clinically-informative parameters. Here,
we demonstrate a rigorous approach to estimating the sensitivity, specificity,
and prediction increment of an EMT marker to assess cancer cell detachment from
primary tumors. METHODS: We illustrate the approach using immunohistochemical
measurements of the EMT marker E-cadherin in a set of colorectal primary tumors
from a population-based prospective cohort in North Carolina. Bayesian latent
class analysis was used to estimate sensitivity and specificity in a setting of
multiple imperfect diagnostic tests and no gold standard. Risk reclassification
analysis was used to assess the extent to which addition of the marker to the
panel of established diagnostic tests would improve mortality prediction. We
explored how changing the latent class conditional dependence assumptions and
definition of marker positivity would impact the results. RESULTS: All diagnostic
accuracy and prediction increment statistics varied with the choice of cut point
to define marker positivity. When comparing different definitions of marker
positivity to each other, numerous trade-offs were observed in terms of
sensitivity, specificity, predictive discrimination, and prediction model
calibration. We then discussed several implementation considerations and the
plausibility of analytic assumptions. CONCLUSIONS: The approaches presented here
can be extended to any EMT marker, to most forms of cancer, and to different
kinds of EMT marker measurements, such as RNA or gene methylation data. These
methods provide valid, clinically-informative assessment of whether and how to
use a given EMT marker to refine tumor staging and consequent treatment
decisions.
PMID- 29338704
TI - Alcohol marketing on YouTube: exploratory analysis of content adaptation to
enhance user engagement in different national contexts.
AB - BACKGROUND: We know little about how social media alcohol marketing is utilized
for alcohol promotion in different national contexts. There does not appear to be
any academic work on online exposure to alcohol marketing via social media in
India, and most of the limited research in Australia has focused on Facebook.
Hence, the present study extends previous research by investigating alcohol
promotion conducted on an under-researched form of social media (YouTube) in two
contrasting geographic contexts. This study examines and compares the types of
strategies used by marketers on Indian and Australian alcohol brands with the
greatest YouTube presence, and the extent to which users engage with these
strategies. METHODS: The 10 alcohol brands per country with the greatest YouTube
presence were identified based on the number of 'subscriptions'. The number of
videos, views per video, and the type of content within the videos were collected
for each brand. The data were analyzed using an inductive coding approach, using
NVivo 10. RESULTS: The targeted brands had gathered 98,881 subscriptions (Indian
brands: n = 13,868; Australian brands: n = 85,013). The type of marketing
strategies utilized by brands were a mix of those that differed by country (e.g.
sexually suggestive content in India and posts related to the brand's tradition
or heritage in Australia) and generic approaches (e.g. encouraging time- and
event-specific drinking; demonstrations of food/cocktail recipes; camaraderie;
competitions and prize draws; and brand sponsorship at music, sports, and fashion
events). CONCLUSIONS: This cross-national comparison demonstrates that YouTube
provides alcohol marketers with an advertising platform where they utilize
tailored marketing approaches to cater to specific national contexts and develop
content on the cultural meanings users invoke in their interactions with these
strategies. Those exposed to alcohol marketing on YouTube are likely to include
those under the legal drinking age.
PMID- 29338705
TI - Frailty as a predictor of hospital length of stay after elective total joint
replacements in elderly patients.
AB - BACKGROUND: Total joint replacement procedures are increasing in number because
of population aging and osteoarthritis development. Defined as a lack of
physiological reserves and the inability to adequately respond to external
stressors, frailty may be more common than expected in older patients with
degenerative arthritis awaiting total joint replacements. The aim of the present
study was to assess associations between frailty and adverse outcomes, frailty
prevalence among elderly patients awaiting elective TJR, and agreement between 2
frailty screening instruments. METHODS: We undertook a prospective,
observational, pilot study in our institution. We enrolled patients 65 years or
older who were awaiting elective knee or hip replacement surgery and evaluated
them in our preoperative clinic with planned postoperative hospital length of
stay greater than 24 h. Patients were asked to grade their perceived well-being
on the Clinical Frailty Scale and to answer questions on the FRAIL Scale.
RESULTS: The Clinical Frailty Scale classified 40 patients (45.9%) as robust, 43
patients (49.4%) as prefrail and 4 patients (4.5%) as frail, while the FRAIL
Scale categorized 12 patients (13.7%) as robust, 54 patients (62.0%) as prefrail,
and 20 patients (22.9%) as frail. Robustness, ascertained on the Clinical Frailty
Scale was, while the FRAIL Scale was not, significantly associated with shorter
hospital length of stay and fewer discharges to the rehabilitation center. Both
scales showed moderate mutual agreement. CONCLUSION: Screening for frailty
identified between 5% and 10% of patients at risk of adverse outcomes. The
Clinical Frailty Scale was, while the FRAIL scale was not, significantly
associated with hospital length of stay and discharge to rehabilitation center in
our cohort of total joint replacement patients.
PMID- 29338706
TI - Miliary tuberculosis with co-existing pulmonary cryptococcosis in non-HIV patient
without underlying diseases: a case report.
AB - BACKGROUND: Tuberculosis and cryptococcosis co-infection usually occurs in
immunosuppressed patients with impaired cell-mediated immunity. However, there
are few reports about such co-infection in non-HIV patients without underlying
diseases. Here, we report a case of miliary tuberculosis with co-existing
pulmonary cryptococcosis in non-HIV patient without underlying diseases. CASE
PRESENTATION: An 84-year-old Asian female presented to our hospital with
complaints of a 1-week history of abdominal pain and appetite loss. Chest
computed tomography (CT) showed diffuse micronodules in random patterns in both
lung fields. Liver, skin and bone marrow biopsies showed epithelioid cell
granuloma. Polymerase chain reaction of gastric aspirate was positive for
Mycobacterium tuberculosis. According to these findings, miliary tuberculosis was
suspected and antimycobacterial therapy was initiated. After a 6-month treatment
course, chest radiograph showed new multiple nodules in the right middle lung
field. Chest CT showed that a right S6 small nodule was increased and new
multiple nodules appeared in the right lower lobe. Flexible fiberoptic
bronchoscopy was subsequently perfomed. Cytology of the bronchial lavage showed a
small number of Periodic acid-Schiff-positive bodies, suggesting Cryptococcus
species. Moreover, serum cryptococcal antigen testing was positive. According to
these findings, pulmonary cryptococcosis was diagnosed, although the culture was
negative. Oral fluconazole therapy was subsequently initiated. After a 6-month
treatment course, chest radiograph showed gradual improvement. CONCLUSION:
Although tuberculosis and cryptococcosis co-infection is relatively rare in
immunocompromised hosts, such as those with acquired immunodeficiency syndrome,
clinicians should be aware that these infections can co-exist even in non-HIV
patients without underlying diseases.
PMID- 29338707
TI - Is the likelihood of spousal violence lower or higher among childless women?
Evidence from Nigeria demographic and health surveys.
AB - BACKGROUND: Few studies have been able to determine whether the likelihood of
spousal violence is higher or lower among childless women compared with women who
have children. This is because most studies linking childlessness and spousal
violence were either qualitative or were conducted among childless women
attending fertility clinics. In the fewer quantitative studies that linked
childlessness and spousal violence, results are mixed and yet to be verified in
Nigeria using nationally representative sample data. The current study addresses
this knowledge gap by raising the research question: is the likelihood of spousal
violence lower or higher among childless women? METHODS: The study analysed data
from 2008 and 2013 Nigeria Demographic and Health Surveys. Only women aged 35-49
years are included in the analysis. The outcome variable was spousal violence,
while the key explanatory variable was parity status categorised into childless,
have only one child, and have two or more children. Selected individual-level and
community-level variables were included as additional explanatory variables. The
multilevel mixed-effects logistic regression analysis was applied in four nested
models using Stata 12. RESULTS: In Model 1, result show 57% more likelihood of
spousal violence among women who have two or more children compared with
childless women (OR = 1.570: CI: 1.074-2.294). In Model 2, women who have two or
more children were 52.3% more likely to experience spousal violence compared with
childless women (OR = 1.523; CI: 1.037-2.247). In Model 3, the likelihood of
spousal violence was 67.2% higher among women who have two or more children
compared with childless women (OR = 1.672; CI: 1.140-2.452). In the full model,
women who have two or more children were 50.8% more likely to experience spousal
violence compared with childless women (OR = 1.508; CI: 1.077-2.234). The Intra
Class Correlation (ICC) provides evidence to support community contributions to
prevalence of spousal violence. CONCLUSIONS: The likelihood of spousal violence
is lower among childless women in Nigeria. Causes of spousal violence against
women cut across individual, family, and community characteristics irrespective
of childlessness or number of children. Current Behaviour Change Communication
should be strengthened by adequate enforcement of the newly enacted Violence
Against Persons (Prohibition) Act of 2015.
PMID- 29338708
TI - Patterns of illness disclosure among Indian slum dwellers: a qualitative study.
AB - BACKGROUND: Slum dwellers display specific traits when it comes to disclosing
their illnesses to professionals. The resulting actions lead to poor health
seeking behaviour and underutilisation of existing formal health facilities. The
ways that slum people use to communicate their feelings about illness, the type
of confidants that they choose, and the supportive and unsupportive social and
cultural interactions to which they are exposed have not yet been studied in the
Indian context, which constitutes an important knowledge gap for Indian
policymakers and practitioners alike. To that end, this study examines the
patterns of illness disclosure in Indian slums and the underpinning factors which
shape the slum dwellers' disclosing attitude. METHODS: In-depth, semi-structured
interviews were conducted among 105 men and 113 women who experienced illness in
the year prior to the study period. Respondents were selected from four urban
slums in two Indian cities, Bangalore and Kolkata. RESULTS: Findings indicate
that women have more confidants at different social levels, while men have a
limited network of disclosures which is culturally and socially mediated. Gender
role limitations, exclusion from peer groups and unsupportive local situations
are the major cause of disclosure delay or non-disclosure among men, while the
main concerns for women are a lack of proper knowledge about illness,
unsupportive responses received from other people on certain occasions, the fear
of social stigma, material loss and the burden of the local situation. Prompt
sharing of illness among men is linked with prevention intention and coping with
biological problems, whereas factors determining disclosure for women relate to
ensuring emotional and instrumental safety, preventing collateral damage of
illness, and preventing and managing biological complications. CONCLUSIONS: The
findings reveal that patterns of disclosure are not determined by the
acknowledgment of illness but largely depend on the interplay between individual
agency, disclosure consequences and the socio cultural environment. The results
of this study can contribute significantly to mitigating the pivotal knowledge
gap between health policymakers, practitioners and patients, leading to the
formulation of policies that maximise the utilisation of health facilities in
slums.
PMID- 29338709
TI - WorMachine: machine learning-based phenotypic analysis tool for worms.
AB - BACKGROUND: Caenorhabditis elegans nematodes are powerful model organisms, yet
quantification of visible phenotypes is still often labor-intensive, biased, and
error-prone. We developed WorMachine, a three-step MATLAB-based image analysis
software that allows (1) automated identification of C. elegans worms, (2)
extraction of morphological features and quantification of fluorescent signals,
and (3) machine learning techniques for high-level analysis. RESULTS: We examined
the power of WorMachine using five separate representative assays: supervised
classification of binary-sex phenotype, scoring continuous-sexual phenotypes,
quantifying the effects of two different RNA interference treatments, and
measuring intracellular protein aggregation. CONCLUSIONS: WorMachine is suitable
for analysis of a variety of biological questions and provides an accurate and
reproducible analysis tool for measuring diverse phenotypes. It serves as a
"quick and easy," convenient, high-throughput, and automated solution for
nematode research.
PMID- 29338710
TI - A genetically encoded Ca2+ indicator based on circularly permutated sea anemone
red fluorescent protein eqFP578.
AB - BACKGROUND: Genetically encoded calcium ion (Ca2+) indicators (GECIs) are
indispensable tools for measuring Ca2+ dynamics and neuronal activities in vitro
and in vivo. Red fluorescent protein (RFP)-based GECIs have inherent advantages
relative to green fluorescent protein-based GECIs due to the longer wavelength
light used for excitation. Longer wavelength light is associated with decreased
phototoxicity and deeper penetration through tissue. Red GECI can also enable
multicolor visualization with blue- or cyan-excitable fluorophores. RESULTS: Here
we report the development, structure, and validation of a new RFP-based GECI, K
GECO1, based on a circularly permutated RFP derived from the sea anemone
Entacmaea quadricolor. We have characterized the performance of K-GECO1 in
cultured HeLa cells, dissociated neurons, stem-cell-derived cardiomyocytes,
organotypic brain slices, zebrafish spinal cord in vivo, and mouse brain in vivo.
CONCLUSION: K-GECO1 is the archetype of a new lineage of GECIs based on the RFP
eqFP578 scaffold. It offers high sensitivity and fast kinetics, similar or better
than those of current state-of-the-art indicators, with diminished lysosomal
accumulation and minimal blue-light photoactivation. Further refinements of the K
GECO1 lineage could lead to further improved variants with overall performance
that exceeds that of the most highly optimized red GECIs.
PMID- 29338711
TI - Blood parasite infections in a wild population of ravens (Corvus corax) in
Bulgaria.
AB - BACKGROUND: Blood parasites have been studied intensely in many families of avian
hosts, but corvids, a particularly cosmopolitan family, remain underexplored.
Haemosporidian parasites of the common raven (Corvus corax) have not been
studied, although it is the largest, most adaptable, and widespread corvid.
Genetic sequence data from parasites of ravens can enhance the understanding of
speciation patterns and specificity of haemosporidian parasites in corvids, and
shed light how these hosts cope with parasite pressure. METHODS: A baited cage
trap was used to catch 86 ravens and a nested PCR protocol was used to amplify a
479 bp fragment of the haemosporidian cytochrome b gene from the samples. The
obtained sequences were compared with the MalAvi database of all published
haemosporidian lineages and a phylogenetic tree including all detected raven
parasites was constructed. An examination of blood smears was performed for
assessment of infection intensity. RESULTS: Twenty blood parasite lineages were
recovered from ravens caught in a wild population in Bulgaria. The prevalence of
generalist Plasmodium lineages was 49%, and the prevalence of Leucocytozoon
lineages was 31%. Out of 13 detected Leucocytozoon lineages six were known from
different corvids, while seven others seem to be specific to ravens. A
phylogenetic reconstruction suggests that Leucocytozoon lineages of ravens and
other corvids are not monophyletic, with some groups appearing closely related to
parasites of other host families. CONCLUSIONS: Several different, morphologically
cryptic groups of Leucocytozoon parasites appear to infect corvids. Ravens
harbour both generalist corvid Leucocytozoon as well as apparently species
specific lineages. The extraordinary breeding ecology and scavenging lifestyle
possibly allow ravens to evade vectors and have relatively low blood parasite
prevalence compared to other corvids.
PMID- 29338712
TI - Association between the level of education and knowledge, attitudes and practices
regarding dengue in the Caribbean region of Colombia.
AB - BACKGROUND: Community integration in dengue control requires assessments of
knowledge, attitudes and practices (KAPs), which can vary widely according to
demographic and educational factors. We aimed to describe and compare the KAPs
according to level of education in municipalities in the Caribbean region of
Colombia. METHODS: A survey was administered from October to December 2015,
including families selected through probabilistic sampling in eleven
municipalities. The analysis focused on the comparative description of the
responses according to level of education. The KAP prevalence ratios (PR)
according to education were estimated using Poisson regression (robust),
including age and sex as adjustment variables. RESULTS: Out of 1057 participants,
1054 (99.7%) surveys were available for analysis, including 614 (58.3%) who had a
high school level of education or higher and 440 (41.7%) who had a lower level of
education (not high school graduates). The high school graduates showed a higher
frequency of correct answers in relation to knowledge about dengue symptoms and
transmission. On the other hand, graduates showed a higher probability of
practices and attitudes that favor dengue control, including not storing water in
containers (PR: 2.2; 95% Confidence Interval [CI]: 1.42-3.43), attend community
meetings (PR: 1.33; 95% CI: 1.07-1.65), educate family members and neighbors in
prevention measures (PR: 1.35; 95% CI: 1.15-1.59). CONCLUSIONS: Level of
education could be a key determinant of knowledge of the disease and its
transmission, as well as attitudes and practices, especially those that involve
the integration of community efforts for dengue control.
PMID- 29338713
TI - LncRNA DANCR involved osteolysis after total hip arthroplasty by regulating FOXO1
expression to inhibit osteoblast differentiation.
AB - BACKGROUND: Aseptic loosening of artificial hip joint is a major complication
affecting the long-term use of the artificial hip joint, and is the main cause of
joint replacement failure. However, the mechanism of aseptic loosening of THR has
not yet cleared. The aim of this study was to investigate the underlying
mechanism of DANCR in osteoblast differentiation (OD). METHODS: We detected the
expressions of DANCR and FOXO1 in clinical samples and mesenchymal stem cells
(MSCs) by qRT-PCR and western blotting. The effects of polymethylmethacrylate
(PMMA) on OD of MSCs were examined by alkaline phosphatase (ALP) activity and
Alizarin Red S (ARS) staining. The expressions of OD markers were measured by qRT
PCR and western blotting. The mechanism of DANCR in OD was detected by RNA pull
down, RNA immunoprecipitation (RIP) assay and ubiquitination assays. RESULTS:
Compared with the surrounding normal tissues, DANCR expression was up-regulated
and FOXO1 expression was down-regulated in periprosthetic tissues. PMMA
suppressed ALP activity, increased DANCR expression, and decreased the
expressions of FOXO1, Runx2, Osterix (Ostx) and osteocalcin (OCN). ARS staining
showed that PMMA inhibited the OD of MSCs. Knockdown of DANCR attenuated the
inhibitory effect of PMMA on OD. Knockdown of FOXO1 could reverse the effect of
si-DANC. RNA pull-down and RIP assay implicated that DANCR bound to FOXO1.
Ubiquitination assay indicated that si-DANCR could repress Skp2-mediated
ubiquitination of FOXO1. CONCLUSION: LncRNA DANCR could inhibit OD by regulating
FOXO1 expression.
PMID- 29338714
TI - The effects of metformin in type 1 diabetes mellitus.
AB - BACKGROUND: This retrospective study investigated the effect of adding metformin
to pharmacologic insulin dosing in type 1 diabetics on insulin therapy 1 year
after treatment compared with patients on insulin therapy alone. METHODS: Twenty
nine adults with type 1 diabetes who had metformin added to their insulin therapy
for 12 months were compared with 29 adults with type 1 diabetes who remained on
insulin-alone therapy. RESULTS: Fifty-eight patients with C peptide negative-type
1 diabetics (26 females, mean age: 29.01 +/- 7.03 years, BMI: 24.18 +/- 3.16
kg/m2) were analyzed. Age, sex, body weight, insulin dose requirement, plasma
glucose (PG), blood pressure (BP), and lipids did not differ between groups
before treatment (p > 0.05). Metabolic syndrome (44.8 vs 41.4%, p > 0.05) did not
differ between the metformin-insulin and insulin alone groups before treatment.
Metabolic syndrome was more decreased in the metformin-insulin group than in the
insulin alone group after treatment (-8.9 +/- 1.3 vs. 2.5 +/- 0.6%, p = 0.028).
Insulin dose requirement was lower in the metformin-insulin group than in the
insulin alone group (-0.03 vs. 0.11 IU/kg/d, p = 0.006). Fasting PG (-26.9 +/-
54.2 vs. 0.7 +/- 29.5 mg/dL, p = 0.022) and postprandial PG (-43.1 +/- 61.8 mg/dL
vs. -3.1 +/- 40.1 mg/dL, p = 0.010) was more decreased in the metformin-insulin
group than in the insulin alone group. Body weight, lipids, and HbA1c did not
differ between the groups (p > 0.05). CONCLUSIONS: Metformin decreased glucose
concentrations, reduced metabolic syndrome, as well as insulin dose requirement
more than insulin therapy alone, 1 year after treatment. These results were
independent of blood lipid improvement or weight loss, although on average weight
remained decreased with metformin-insulin therapy, whereas the average weight
increased with insulin therapy alone.
PMID- 29338715
TI - Landscape genomics: natural selection drives the evolution of mitogenome in
penguins.
AB - BACKGROUND: Mitochondria play a key role in the balance of energy and heat
production, and therefore the mitochondrial genome is under natural selection by
environmental temperature and food availability, since starvation can generate
more efficient coupling of energy production. However, selection over
mitochondrial DNA (mtDNA) genes has usually been evaluated at the population
level. We sequenced by NGS 12 mitogenomes and with four published genomes,
assessed genetic variation in ten penguin species distributed from the equator to
Antarctica. Signatures of selection of 13 mitochondrial protein-coding genes were
evaluated by comparing among species within and among genera (Spheniscus,
Pygoscelis, Eudyptula, Eudyptes and Aptenodytes). The genetic data were
correlated with environmental data obtained through remote sensing (sea surface
temperature [SST], chlorophyll levels [Chl] and a combination of SST and Chl
[COM]) through the distribution of these species. RESULTS: We identified the
complete mtDNA genomes of several penguin species, including ND6 and 8 tRNAs on
the light strand and 12 protein coding genes, 14 tRNAs and two rRNAs positioned
on the heavy strand. The highest diversity was found in NADH dehydrogenase genes
and the lowest in COX genes. The lowest evolutionary divergence among species was
between Humboldt (Spheniscus humboldti) and Galapagos (S. mendiculus) penguins
(0.004), while the highest was observed between little penguin (Eudyptula minor)
and Adelie penguin (Pygoscelis adeliae) (0.097). We identified a signature of
purifying selection (Ka/Ks < 1) across the mitochondrial genome, which is
consistent with the hypothesis that purifying selection is constraining
mitogenome evolution to maintain Oxidative phosphorylation (OXPHOS) proteins and
functionality. Pairwise species maximum-likelihood analyses of selection at codon
sites suggest positive selection has occurred on ATP8 (Fixed-Effects Likelihood,
FEL) and ND4 (Single Likelihood Ancestral Counting, SLAC) in all penguins. In
contrast, COX1 had a signature of strong negative selection. ND4 Ka/Ks ratios
were highly correlated with SST (Mantel, p-value: 0.0001; GLM, p-value: 0.00001)
and thus may be related to climate adaptation throughout penguin speciation.
CONCLUSIONS: These results identify mtDNA candidate genes under selection which
could be involved in broad-scale adaptations of penguins to their environment.
Such knowledge may be particularly useful for developing predictive models of how
these species may respond to severe climatic changes in the future.
PMID- 29338716
TI - Donor age affects proteome composition of tenocyte-derived engineered tendon.
AB - BACKGROUND: The concept of tissue engineering is to deliver to the injury site
biological scaffolds carrying functional cells that will enhance healing
response. The preferred cell source is autologous in order to reduce immune
response in the treated individual. However, in elderly patients age-related
changes in synthetic activity of the implanted cells and subsequent alterations
in tissue protein content may affect therapeutic outcomes. In this study we
investigated the effect of donor age on proteome composition of tenocyte-derived
tendon tissue-engineered constructs. RESULTS: Liquid chromatography tandem mass
spectrometry was used to assess the proteome of tissue-engineered constructs
derived from young and old equine tenocytes. Ageing was associated with altered
extracellular matrix composition, especially accumulation of collagens (type I,
III and XIV), and lower cytoskeletal turnover. Proteins involved in cell
responsiveness to mechanical stimuli and cell-extracellular matrix interaction
(calponin 1, palladin, caldesmon 1, cortactin) were affected. CONCLUSIONS: This
study demonstrated significant changes in proteome of engineered tendon derived
from young and old tenocytes, indicating the impact of donor age on composition
of autologous constructs.
PMID- 29338717
TI - Risk factors for acute respiratory infections in children under five years
attending the Bamenda Regional Hospital in Cameroon.
AB - BACKGROUND: Acute respiratory infections (ARI) are a leading cause of morbidity
and mortality in under-five children worldwide. About 6.6 million children less
than 5 years of age die every year in the world; 95% of them in low-income
countries and one third of the total deaths is due to ARI. This study aimed at
determining the proportion of acute respiratory infections and the associated
risk factors in children under 5 years visiting the Bamenda Regional Hospital in
Cameroon. METHODS: A cross-sectional analytic study involving 512 children under
5 years was carried out from December 2014 to February 2015. Participants were
enrolled by a consecutive convenient sampling method. A structured questionnaire
was used to collect clinical, socio-demographic and environmental data. Diagnosis
of ARI was based on the revised WHO guidelines for diagnosing and management of
childhood pneumonia. The data was analyzed using the statistical software
EpiInfoTM version 7. RESULTS: The proportion of ARIs was 54.7% (280/512), while
that of pneumonia was 22.3% (112/512). Risk factors associated with ARI were: HIV
infection ORadj 2.76[1.05-7.25], poor maternal education (None or primary only)
ORadj 2.80 [1.85-4.35], exposure to wood smoke ORadj 1.85 [1.22-2.78], passive
smoking ORadj 3.58 [1.45-8.84] and contact with someone who has cough ORadj 3.37
[2.21-5.14]. Age, gender, immunization status, breastfeeding, nutritional status,
fathers' education, parents' age, school attendance and overcrowding were not
significantly associated with ARI. CONCLUSION: The proportion of ARI is high and
is associated with HIV infection, poor maternal education, exposure to wood
smoke, passive cigarette smoking, and contact with persons having a cough.
Control programs should focus on diagnosis, treatment and prevention of ARIs.
PMID- 29338718
TI - A live cell assay of GPCR coupling allows identification of optogenetic tools for
controlling Go and Gi signaling.
AB - BACKGROUND: Animal opsins are light-sensitive G-protein-coupled receptors (GPCRs)
that enable optogenetic control over the major heterotrimeric G-protein signaling
pathways in animal cells. As such, opsins have potential applications in both
biomedical research and therapy. Selecting the opsin with the best balance of
activity and selectivity for a given application requires knowing their ability
to couple to a full range of relevant Galpha subunits. We present the GsX assay,
a set of tools based on chimeric Gs subunits that transduce coupling of opsins to
diverse G proteins into increases in cAMP levels, measured with a real-time
reporter in living cells. We use this assay to compare coupling to Gi/o/t across
a panel of natural and chimeric opsins selected for potential application in gene
therapy for retinal degeneration. RESULTS: Of the opsins tested, wild-type human
rod opsin had the highest activity for chimeric Gs proxies for Gi and Gt (Gsi and
Gst) and was matched in Go proxy (Gso) activity only by a human rod opsin/scallop
opsin chimera. Rod opsin drove roughly equivalent responses via Gsi, Gso, and
Gst, while cone opsins showed much lower activities with Gso than Gsi or Gst, and
a human rod opsin/amphioxus opsin chimera demonstrated higher activity with Gso
than with Gsi or Gst. We failed to detect activity for opsin chimeras bearing
three intracellular fragments of mGluR6, and observed unexpectedly complex
response profiles for scallop and amphioxus opsins thought to be specialized for
Go. CONCLUSIONS: These results identify rod opsin as the most potent non
selective Gi/o/t-coupled opsin, long-wave sensitive cone opsin as the best for
selectively activating Gi/t over Go, and a rod opsin/amphioxus opsin chimera as
the best choice for selectively activating Go over Gi/t.
PMID- 29338719
TI - Preventing malaria in the Peruvian Amazon: a qualitative study in Iquitos, Peru.
AB - BACKGROUND: In Peru, despite decades of concerted control efforts, malaria
remains a significant public health burden. Peru has recently exhibited a
dramatic rise in malaria incidence, impeding South America's progress towards
malaria elimination. The Amazon basin, in particular the Loreto region of Peru,
has been identified as a target for the implementation of intensified control
strategies, aiming for elimination. No research has addressed why vector control
strategies in Loreto have had limited impact in the past, despite vector control
elsewhere being highly effective in reducing malaria transmission. This study
employed qualitative methods to explore factors limiting the success of vector
control strategies in the region. METHODS: Twenty semi-structured interviews were
conducted among adults attending a primary care centre in Iquitos, Peru, together
with 3 interviews with key informants (health care professionals). The interviews
focussed on how local knowledge, together with social and cultural attitudes,
determined the use of vector control methods. RESULTS: Five themes emerged. (a)
Participants believed malaria to be embedded within their culture, and commonly
blamed this for a lack of regard for prevention. (b) They perceived a shift in
mosquito biting times to early evening, rendering night-time use of bed nets less
effective. (c) Poor preventive practices were compounded by a consensus that
malaria prevention was the government's responsibility, and that this reduced
motivation for personal prevention. (d) Participants confused the purpose of
space-spraying. (e) Participants' responses also exposed persisting
misconceptions, mainly concerning the cause of malaria and best practices for its
prevention. CONCLUSION: To eliminate malaria from the Americas, region-specific
strategies need to be developed that take into account the local social and
cultural contexts. In Loreto, further research is needed to explore the potential
shift in biting behaviour of Anopheles darlingi, and how this interacts with the
population's social behaviours and current use of preventive measures. Attitudes
concerning personal responsibility for malaria prevention and long-standing
misconceptions as to the cause of malaria and best preventive practices also need
to be addressed.
PMID- 29338720
TI - Manual exchange transfusion for severe imported falciparum malaria: a
retrospective study.
AB - BACKGROUND: This study was designed to evaluate the efficacy of exchange
transfusion in patients with severe imported falciparum malaria. Twelve patients
who met the diagnostic criteria for severe malaria were treated with exchange
transfusion 14 times according to a conventional anti-malarial treatment. This
study evaluated the efficacy of exchange transfusion for severe imported
falciparum malaria. METHODS: Clinical data of severe imported falciparum malaria
patients admitted to the intensive care unit (ICU) of Nantong Third People's
Hospital from January 2007 to December 2016 were investigated in this
retrospective study. Patients were divided into the intervention group, which
received exchange transfusion, and the control group. This study assessed
parasite clearance and outcomes of the two groups, and levels of erythrocytes,
haemoglobin, platelets, coagulation, liver function, lactate, C-reactive protein,
and procalcitonin, before and after exchange transfusion in the intervention
group. RESULTS: There was no significant difference in the severity of admitted
patients. Exchange transfusion was successfully applied 14 times in the
intervention group. Differences in the levels of erythrocytes, haemoglobin and
platelets did not reach statistical significance. Exchange transfusion improved
coagulation, liver function, lactic acid, C-reactive protein, and procalcitonin.
No differences were observed in parasite clearance, ICU and hospital length of
stay, in-hospital mortality, and costs of hospitalization between the two groups.
CONCLUSION: Exchange transfusion as adjunctive therapy for severe malaria was
observed to be safe in this setting. Exchange transfusion can improve liver
function and coagulation and reduce inflammation, but it failed to improve
parasite clearance and the outcomes of severe imported falciparum malaria in this
case series.
PMID- 29338721
TI - Infectious keratoconjunctivitis in semi-domesticated Eurasian tundra reindeer
(Rangifer tarandus tarandus): microbiological study of clinically affected and
unaffected animals with special reference to cervid herpesvirus 2.
AB - BACKGROUND: Infectious keratoconjunctivitis (IKC) is one of the most common
ocular diseases in ruminants worldwide. In addition to keratitis and
conjunctivitis, animals with IKC can develop uveitis, corneal ulcer, and in
severe cases, blindness. The bacteria Moraxella spp. has been described as the
primary causative agent of infectious bovine keratoconjunctivitis (IBK) in cattle
(Bos taurus), while Chlamydia spp. and Mycoplasma conjunctivae are considered the
main causative agents of IKC in sheep (Ovis aries). Previous studies indicated
cervid herpesvirus 2 (CvHV2) as the primary causative agent of IKC in semi
domesticated reindeer (Rangifer tarandus tarandus). The aim of the study was to
investigate the presence and prevalence of potential pathogens for IKC in
reindeer, and compare the ocular microbiota of animals with IKC, with apparently
healthy animals. RESULTS: Semi-domesticated reindeer (n = 341), with (n = 108) or
without (n = 113) ocular clinical signs, or with no information on clinical
status (n = 120), were sampled in Norway, Sweden and Finland in 2010-2014.
Seroprevalence was 37.4% for alphaherpesvirus (95/254), 3.8% for gammaherpesvirus
(8/211) and 7.1% for pestivirus (15/211) (ELISA). PCR analyses of conjunctival
swab samples revealed a prevalence of 28.5% for CvHV2 (57/200), 11.9% for
Chlamydiaceae (16/135) and 1.0% for M. conjunctivae (2/197). Bacteriological
cultivation of 202 conjunctival swab samples revealed bacterial growth from 75.2%
of the samples, with Moraxella spp. being isolated from 21.6% (11/51) of the
animals with and 5.6% (5/84) without ocular clinical signs. A significant
association (p < 0.001) existed between the presence of clinical signs of IKC and
CvHV2 DNA in the affected eyes, an association that was not present for other
microorganisms. CONCLUSIONS: These results support the hypothesis that CvHV2 is
the primary agent of IKC in semi-domesticated reindeer in Fennoscandia, with
Moraxella bovoculi being a secondary candidate, since it was isolated in two
different outbreaks of IKC. Further studies should be carried out to better
understand the infection biology and the pathogenesis of IKC in reindeer.
PMID- 29338722
TI - Development and pilot evaluation of a clinic-based mHealth app referral service
to support adult cancer survivors increase their participation in physical
activity using publicly available mobile apps.
AB - BACKGROUND: Participation in regular physical activity holds key benefits for
cancer survivors, yet few cancer survivors meet physical activity
recommendations. This study aimed to develop and pilot test a mHealth app
referral service aimed at assisting cancer survivors to increase their physical
activity. In particular, the study sought to examine feasibility and
acceptability of the service and determine preliminary efficacy for physical
activity behaviour change. METHODS: A systematic search identified potentially
appropriate Apple (iOS) and Android mHealth apps. The apps were audited regarding
the type of physical activity encouraged, evidence-based behavioural strategies
and other characteristics, to help match apps to users' preferences and
characteristics. A structured service was devised to deliver the apps and
counselling, comprising two face-to-face appointments with a mid-week phone or
email check-up. The mHealth app referral service was piloted using a pre-post
design among 12 cancer survivors. Participants' feedback regarding the service's
feasibility and acceptability was sought via purpose-designed questionnaire, and
analysed using inductive thematic analysis and descriptive statistics. Change in
physical activity was assessed using a valid and reliable self-report tool and
analysed using paired t-tests. In line with recommendations for pilot studies,
confidence intervals and effect sizes were reported to aid interpretation of
clinical significance, with an alpha of 0.2 used to denote statistical
significance. RESULTS: Of 374 mHealth apps identified during the systematic
search, 54 progressed to the audit (iOS = 27, Android = 27). The apps
consistently scored well for aesthetics, engagement and functionality, and
inconsistently for gamification, social and behaviour change features. Ten
participants completed the pilot evaluation and provided positive feedback
regarding the service's acceptability and feasibility. On average, participants
increased their moderate-vigorous physical activity by 236 min per week (d =
0.73; 95% CI = -49 to 522; p = 0.09). CONCLUSION: This study offered initial
evidence that a mHealth app referral service for cancer survivors is feasible and
acceptable and may increase physical activity levels. The large increase in
physical activity is promising, but should be interpreted with caution given the
small sample size and lack of control group. Further research is warranted on a
larger scale to investigate generalisability, long-term compliance and
application in clinical settings.
PMID- 29338723
TI - Preventing suicidal behaviours with a multilevel intervention: a cluster
randomised controlled trial.
AB - BACKGROUND: In the context of the recent surge in community based multilevel
interventions for suicide prevention, all of which show promising results, we
discuss the implications of the findings of such an intervention designed for and
implemented in New Zealand. The multi-level intervention for suicide prevention
in New Zealand (MISP-NZ) was a cluster randomised controlled community
intervention trial involving eight hospital regions matched into four pairs and
randomised to either the intervention or practice as usual (the control).
Intervention regions received 25 months of interventions (01 June 2010 to 30 June
2012) including: 1) training in recognition of suicide risk factors; 2) workshops
on mental health issues; 3) community based interventions (linking in with
community events); and 4) distribution of print material and information on web
based resources. RESULTS: There was no significant difference between the change
in rate of suicidal behaviours (ISH or self-inflicted deaths) in the intervention
group compared with the control group (rate ratio = 1.07, 95% CI 0.82, 1.38).
CONCLUSIONS: This study did not provide substantive evidence that the MISP-NZ
intervention had an effect on suicidal behaviours raising important questions
about the potential effectiveness of the multilevel intervention model for
suicide prevention for all countries. Although a range of factors may account for
this unanticipated finding, including inadequate study power, differences in
design and intervention focus, and country-specific contextual factors, it is
possible that the effectiveness of the multilevel intervention model for reducing
suicidal behaviours may have been overstated. TRIAL REGISTRATION: This trial was
retrospectively registered on 11 April 2013. ACTRN12613000399796 .
PMID- 29338724
TI - Development and validation of HPTLC fingerprints of three species of Alpinia with
biomarker Galangin.
AB - BACKGROUND: Alpinia galanga (L.) Willd. commonly called as Rasna, Greater
galangal or Kulinjan is a medicinally important rhizome used in Indian
traditional system of medicine to cure a number of ailments. A. galanga is the
main source of a galangin -a medicinally important flavanol which has a number of
pharmacological properties viz. anti-mutagenic, and anti-inflammatory. Due to the
high demand for the rhizome of A. galanga traders are now substituting it with
rhizomes of A. calcarata and A. officinarum. METHODS: The present study aims to
develop high performance thin layer chromatographic (HPTLC) fingerprinting of A.
galanga with its adulterants or substitutes and to quantify bioactive galangin
present thereof. Methanolic extracts were obtained from rhizomes of the three
species of Alpinia used for HPTLC analysis using silica gel 60 F254 plates and
hexane: ethyl acetate: acetic acid (6.2: 2.8: 1.0 v/v/v); the densitometric
analysis was performed at 272 nm. RESULTS: By comparison of Rf values and of the
spectra of the bands with those of the standard galangin was identified in all
three samples. HPTLC quantitative analysis of the methanolic extracts showed the
decline trend in the quantity of the galangin in the three species of Alpinia as
A. galanga (7.67 +/- 0.36 mg/g) > A. officinarum (5.77 +/- 0.71 mg/g) > A.
calcarata (4.31 +/- 0.44 mg/g). The HPTLC method was validated using
International Conference on Harmonization (ICH) guidelines. The HPTLC method
showed good linearity, recovery and high precision of biomarker. CONCLUSIONS:
Rapid and reproducible method is useful for routine analysis of galangin and
quality control of Alpinia galangal along with its adulterants or substitutes.
PMID- 29338725
TI - Herbal formula YGJDSJ inhibits anchorage-independent growth and induces anoikis
in hepatocellular carcinoma Bel-7402 cells.
AB - BACKGROUND: Based on clinical medications and related studies, we established a
Yang-Gan Jie-Du Sang-Jie (YGJDSJ) herbal formula for hepatocarcinoma treatment.
In present study, we evaluated the anti-cancer potential of YGJDSJ on suspension
grown human hepatocellular carcinoma Bel-7402 cells. METHODS: Bel-7402 cells were
cultured in poly(2-hydroxyethyl methacrylate) (poly-HEMA) coated plates and
treated with YGJDSJ. Anchorage-independent cell growth was detected by cell
Counting Kit-8 (CCK-8) assay and soft agar colony formation assay. Anoikis was
detected by ethdium homodimer-1 (EthD-1) staining and flow cytometry analysis.
Caspases activities were detected by the cleavage of chromogenic substrate.
Reactive oxygen species (ROS) was detected by 2',7'-dichlorofluorescin diacetate
(DCFH-DA) staining. Protein expression and phosphorylation was identified by
western blot. Protein expression was knocked-down by siRNA. RESULTS: YGJDSJ
inhibited the proliferation of Bel-7402 cells in poly-HEMA coated plates and
anchorage-independent growth of Bel-7402 cells in soft agar. YGJDSJ also induced
anoikis in Bel-7402 cells as indicated by EthD-1 staining and flow cytometry
analysis. YGJDSJ activated caspase-3, - 8, and - 9 in suspension-grown Bel-7402
cells. The pan-caspase inhibitor Z-VAD-FMK significantly abrogated the effects of
YGJDSJ on anoikis in suspension-grown Bel-7402 cells. In addition, YGJDSJ
increased ROS in suspension-grown Bel-7402 cells. The ROS scavenger N-acetyl-L
cysteine (NAC) partially attenuated YGJDSJ-induced activation of caspase-3, - 8
and - 9 and anoikis in suspension-grown Bel-7402 cells. Furthermore, YGJDSJ
inhibited expression and phosphorylation of protein tyrosine kinase 2 (PTK2) in
suspension-grown Bel-7402 cells. Over-expression of PTK2 significantly abrogated
YGJDSJ induced anoikis. CONCLUSIONS: YGJDSJ inhibits anchorage-independent growth
and induce caspase-mediated anoikis in Bel-7402 cells, and may relate to ROS
generation and PTK2 downregulation.
PMID- 29338726
TI - A case of blackwater fever with persistent Plasmodium falciparum parasitaemia
detected by PCR after artemether-lumefantrine treatment.
AB - BACKGROUND: Blackwater fever is a complication of malaria infection consisting of
a syndrome of febrile intra-vascular haemolysis with severe anaemia and
intermittent passage of dark-red to black colour urine. Despite numerous reports
and studies of this condition, its pathogenesis remains incompletely understood.
CASE PRESENTATION: This report describes a case of classic blackwater fever in a
returning traveller, without prior history of malaria infection nor usage of anti
malarial prophylaxis, treated with two courses of oral artemether-lumefantrine
combination therapy. Unusual persistence of submicroscopic Plasmodium falciparum
parasitaemia was detected by PCR for 18 days after initiation of treatment.
CONCLUSION: To the authors' knowledge this is the first reported occurrence of a
case of blackwater fever associated with prolonged submicroscopic parasitaemia.
This unusual case challenges the current knowledge of the pathogenesis of this
condition and opens questions that may have important diagnostic and treatment
implications.
PMID- 29338727
TI - Mendelian randomization analysis to assess a causal effect of haptoglobin on
macroangiopathy in Chinese type 2 diabetes patients.
AB - BACKGROUND: Haptoglobin (Hp) functions as an antioxidant by binding with
haemoglobin. We investigated whether serum Hp has a causal effect on
macroangiopathy via Mendelian randomization (MR) analysis with common variants of
the Hp gene in Chinese patients with type 2 diabetes. METHODS: A total of 5687
type 2 diabetes patients were recruited and genotyped for the Hp gene. Clinical
features and vascular imaging tests were applied to diagnose macroangiopathy. The
association between common Hp genotypes and macroangiopathy was analyzed in the
whole population. Serum Hp levels were measured by enzyme-linked immunosorbent
assay in a subset of 935 patients. We individually analyzed the correlations
among Hp levels, Hp genotypes and macroangiopathy. Further, 8-hydroxy-2'
deoxyguanosine (8-OHdG), an oxidative marker of DNA damage, was examined to
evaluate the levels of oxidative stress. RESULTS: Common Hp genotypes were
correlated with macroangiopathy (OR = 1.140 [95% CI 1.005-1.293], P = 0.0410 for
the Hp 1 allele). Serum Hp levels were associated with both common Hp genotypes
(P = 3.55 * 10-31) and macroangiopathy (OR = 2.123 [95% CI 1.098-4.102], P =
0.0252) in the subset of 935 patients. In the MR analysis, the directional trends
of the observed and predicted relationships between common Hp genotypes and
macroangiopathy were the same (OR 1.357 and 1.130, respectively). Furthermore,
common Hp genotypes and Hp levels were associated with serum 8-OHdG levels (P =
0.0001 and 0.0084, respectively). CONCLUSIONS: Our study provides evidence for a
causal relationship between serum Hp levels and macroangiopathy in Chinese type 2
diabetes patients by MR analysis.
PMID- 29338728
TI - Re-evaluation of the definition of remission on the 17-item Hamilton Depression
Rating Scale based on recovery in health-related quality of life in an
observational post-marketing study.
AB - BACKGROUND: Although a score of less than 7 for the 17-item Hamilton Depression
Rating Scale (HAM-D17) has been widely adopted to define remission of depression,
a full recovery from depression is closely related to the patient's quality of
life as well. Accordingly, we re-evaluated this definition of remission using HAM
D17 in comparison with the corresponding score for health-related quality of life
(HRQOL) measured by the SF-36. METHODS: Using the data for depressive patients
reported by GlaxoSmithKline K.K. (Study No. BRL29060A/863) in a post-marketing
observational study of paroxetine, with a sample size of n = 722, multivariate
logistic regression was performed with the HAM-D17 score as a dependent variable
and with each of the eight domain scores of HRQOL (from the SF-36) transformed
into a binominal form according to the national standard value for Japan. Then,
area under curve of receiver operating characteristic analyses were conducted.
Based on the obtained results, a multivariate analysis was performed using the
HAM-D17 score in a binomial form with HAM-D17 as a dependent variable and with
each of the eight HRQOL domain scores (SF-36) as binominalized independent
variables. RESULTS: A cutoff value for the HAM-D17 score of 5 provided the
maximum ROC-AUC at "0.864." The significantly associated scores of the eight
HRQOL domains (SF-36) were identified for the HAM-D17 cutoff values of >=5 and
<=4. The scores for physical functioning (odds ratio, 0.473), bodily pain
(0.557), vitality (0.379), social functioning (0.540), role-emotion (0.265), and
mental health (0.467) had a significant negative association with the HAM-D17
score (p < 0.05), and HRQOL domain scores for HAM-D17 >= 5 were significantly
lower compared with those for HAM-D17 <= 4. CONCLUSIONS: A cutoff value for HAM
D17 of less than or equal to 4 was the best candidate for indicating remission of
depression when the recovery of HRQOL is considered. Restoration of social
function and performance should be considered equally important in assessing the
adequacy of treatment for patients with depression.
PMID- 29338729
TI - Computational study of the effects of arterial bifurcation on the temperature
distribution during cryosurgery.
AB - BACKGROUND: Thermally significant blood flows into locally cooled diseased
tissues and warm them during cryosurgery so that the iceball is often hard to
cover the whole diseased volume. This paper is aimed at investigating the effects
of large arterial bifurcation on the temperature distribution during cryosurgery
through simulation method. METHODS: A parametric geometry model is introduced to
construct a close-to-real arterial bifurcation. The three-dimensional transient
conjugate heat transfer between bifurcated artery and solid tissues with phase
change during cryosurgery is performed by finite volume method. RESULTS: The
discussion was then made on the effects of the relative position between
cryoprobe and artery bifurcation, the inlet velocity of root artery and the
layout of multiple cryoprobes on the temperature distribution and iceball
evolution. The results show that the thermal interaction between blood flow and
iceball growth near bifurcation is considerable complex. The thermal effects of
bifurcation could modulate the iceball morphology, severely weaken its freezing
volume and prevent the blood vessel from being frozen. CONCLUSION: The present
work is expected to be valuable in optimizing cryosurgery scheme of the situation
that the bifurcated artery is embedded into the disease tissue.
PMID- 29338730
TI - Factors associated with HIV positive sero-status among exposed infants attending
care at health facilities: a cross sectional study in rural Uganda.
AB - BACKGROUND: East and South Africa contributes 59% of all pediatric HIV infections
globally. In Uganda, HIV prevalence among HIV exposed infants was estimated at
5.3% in 2014. Understanding the remaining bottlenecks to elimination of mother-to
child transmission (eMTCT) is critical to accelerating efforts towards eMTCT.
This study determined factors associated with HIV positive sero-status among
exposed infants attending mother-baby care clinics in rural Kasese so as to
inform enhancement of interventions to further reduce MTCT. METHODS: This was a
cross-sectional mixed methods study. Quantitative data was derived from routine
service data from the mother's HIV care card and exposed infant clinical chart.
Key informant interviews were conducted with health workers and in-depth
interviews with HIV infected mothers. Quantitative data was analyzed using Stata
version 12. Logistic regression was used to determine factors associated with HIV
sero-status. Latent content analysis was used to analyse qualitative data.
RESULTS: Overall, 32 of the 493 exposed infants (6.5%) were HIV infected. Infants
who did not receive ART prophylaxis at birth (AOR = 4.9, 95% CI: 1.901-13.051,
p=0.001) and those delivered outside of a health facility (AOR = 5.1, 95% CI:
1.038 - 24.742, p = 0.045) were five times more likely to be HIV infected than
those who received prophylaxis and those delivered in health facilities,
respectively. Based on the qualitative findings, health system factors affecting
eMTCT were long waiting time, understaffing, weak community follow up system,
stock outs of Neverapine syrup and lack of HIV testing kits. CONCLUSION:
Increasing facility based deliveries and addressing underlying health system
challenges related to staffing and availability of the required commodities may
further accelerate eMTCT.
PMID- 29338731
TI - Effective nationwide school-based participatory extramural program on adolescent
body mass index, health knowledge and behaviors.
AB - BACKGROUND: Adolescent obesity is a major public health concern. Open to all high
school students regardless of weight status, HealthCorps is a nationwide program
offering a comprehensive high school-based participatory educational program to
indirectly address obesity. We tested a hypothesis that the HealthCorps program
would decrease BMI z-scores among overweight or obese students, and reduce
obesity rates, and evaluated its effects on health knowledge and behaviors.
METHODS: HealthCorps aimed to improve student knowledge and behaviors regarding
nutrition quality, physical activity, sleep, breakfast intake, and mental
resilience. Participating students received through HealthCorps coordinators
weekly or bi-weekly classroom lessons either for a semester or a year in addition
to various during- and after-school health-promoting activities and mentorship.
Self-reported height and weight were collected along with questionnaires
assessing knowledge and behaviors during 2013-2014 academic year among 14
HealthCorps-participating New York City high schools. This quasi experimental two
arm pre-post trial included 611 HealthCorps and 221 comparison arm students for
the analytic sample. Sex-specific analyses stratified by weight status were
adjusted for age and Hispanic ethnicity with clustering effects of schools and
students taken into account. RESULTS: HealthCorps female overweight/obese and
obese student had a significant decrease in BMI z-scores (post-pre delta BMI z
score = -0.16 (95%CI = (-0.26, -0.05), p = 0.004 for the former; and = -0.23 (
0.44, -0.03), p = 0.028, for the latter) whereas comparison female counterparts
did not. The HealthCorps students, but not the comparison students, had a
significant increase for all knowledge domains except for the breakfast realm,
and reported a greater number of significant behavior changes including fruit and
vegetable intake and physical activities. CONCLUSIONS: The HealthCorps program
was associated with reduced BMI z-score in overweight/obese and obese female
adolescents, with enhanced health knowledge and behavior for both sexes. With its
wide reach, this may be a promising program to help combat adolescent obesity in
schools. TRIAL REGISTRATION: This study is registered as a clinical trial at the
ClinicalTrials.gov registry with trial number NCT02277496 on September 10, 2014
(Retrospectively registered).
PMID- 29338732
TI - Transcriptional profile and Epstein-Barr virus infection status of laser-cut
immune infiltrates from the brain of patients with progressive multiple
sclerosis.
AB - BACKGROUND: It is debated whether multiple sclerosis (MS) might result from an
immunopathological response toward an active Epstein-Barr virus (EBV) infection
brought into the central nervous system (CNS) by immigrating B cells. Based on
this model, a relationship should exist between the local immune milieu and EBV
infection status in the MS brain. To test this hypothesis, we analyzed expression
of viral and cellular genes in brain-infiltrating immune cells. METHODS: Twenty
three postmortem snap-frozen brain tissue blocks from 11 patients with
progressive MS were selected based on good RNA quality and prominent immune cell
infiltration. White matter perivascular and intrameningeal immune infiltrates,
including B cell follicle-like structures, were isolated from brain sections
using laser capture microdissection. Enhanced PCR-based methods were used to
investigate expression of 75 immune-related genes and 6 EBV genes associated with
latent and lytic infection. Data were analyzed using univariate and multivariate
statistical methods. RESULTS: Genes related to T cell activation, cytotoxic cell
mediated (or type 1) immunity, B cell growth and differentiation, pathogen
recognition, myeloid cell function, type I interferon pathway activation, and
leukocyte recruitment were found expressed at different levels in most or all MS
brain immune infiltrates. EBV genes were detected in brain samples from 9 of 11
MS patients with expression patterns suggestive of in situ activation of latent
infection and, less frequently, entry into the lytic cycle. Comparison of data
obtained in meningeal and white matter infiltrates revealed higher expression of
genes related to interferongamma production, B cell differentiation, cell
proliferation, lipid antigen presentation, and T cell and myeloid cell
recruitment, as well as more widespread EBV infection in the meningeal samples.
Multivariate analysis grouped genes expressed in meningeal and white matter
immune infiltrates into artificial factors that were characterized primarily by
genes involved in type 1 immunity effector mechanisms and type I interferon
pathway activation. CONCLUSION: These results confirm profound in situ EBV
deregulation and suggest orchestration of local antiviral function in the MS
brain, lending support to a model of MS pathogenesis that involves EBV as
possible antigenic stimulus of the persistent immune response in the central
nervous system.
PMID- 29338733
TI - Effect of metatarsal osteotomy and open lateral soft tissue procedure on sesamoid
position: radiological assessment.
AB - BACKGROUND: Incomplete sesamoid reduction is a potential risk factor for the
recurrence of hallux valgus. The purpose of this study was to radiologically
investigate changes in sesamoid position after chevron osteotomy and the open
lateral soft tissue procedure. METHODS: Sixty-eight feet that underwent operative
correction for hallux valgus deformity were reviewed consecutively. The hallux
valgus angle (HVA), first to second intermetatarsal angle (IMA), tibial sesamoid
position (TSP), distance of the fibular sesamoid (DFS), and translation of the
metatarsal head (TMH) were evaluated preoperatively and at final follow-up.
RESULTS: While most parameters were significantly decreased after surgery, no
significant change in DFS (correction - 1.45 mm, p = 0.08) was noted. The
difference between preoperative and postoperative TSP values (DeltaTSP) has a
moderately positive correlation with difference in TMH values (DeltaTMH) (Rho
0.475, p = .000). Other parameters were similarly correlated. CONCLUSIONS: First,
metatarsal bone realignment reduced the sesamoid, but its position, relative to
the second metatarsal axis (DFS), was unchanged. The sesamoid is reduced by the
lateral translation of the first metatarsal but not by medial sesamoid migration.
PMID- 29338734
TI - Comparing the benefits of chemoradiotherapy and chemotherapy for resectable stage
III A/N2 non-small cell lung cancer: a meta-analysis.
AB - BACKGROUND: Induction chemotherapy has been shown to improve survival of patients
with stage III A/N2 (T1-3, N2, M0) non-small cell lung cancer (NSCLC), followed
by resection, but the benefits of neoadjuvant radiotherapy still remain
controversial. METHODS: PubMed, Embase, and Cochrane library databases were
searched for relevant randomized controlled trials (RCTs) comparing the outcomes
of induction chemoradiotherapy over induction chemotherapy, in patients with
resectable stage IIIA/N2 NSCLC. Odds ratios (ORs) with corresponding 95%
confidence intervals (95% CIs) were calculated using random- or fixed-effects
model, and heterogeneity was assessed using I2 test. Publication bias was
examined by funnel plots analysis. RESULTS: A total of three RCTs met the
inclusion criteria of our meta-analysis. The pooled results demonstrated that, in
comparison to induction chemotherapy, induction chemoradiotherapy has a
significant benefit in tumor response, mediastinal downstaging, and pathological
complete response of mediastinal lymph nodes. In addition, no more peri
intervention mortality was detected in patients from chemoradiotherapy group, and
a higher number of patients from this group had R0 resection. However, our
results did not show any difference between overall survival and progression-free
survival after 2, 4, and 6 years of follow-ups, in patients undergoing radiation
therapy vs. induction chemotherapy. CONCLUSION: Preoperative chemoradiotherapy,
as compared to induction chemotherapy alone, is associated with similar peri
intervention mortality, a greater tumor response, mediastinal nodule downstaging,
and rate of R0 resection, but does not improve survival of resectable stage
IIIA/N2 NSCLC patients.
PMID- 29338735
TI - Mental health service utilization is associated with retention in care among
persons living with HIV at a university-affiliated HIV clinic.
AB - BACKGROUND: Mental health (MH) comorbidities reduce retention in care for persons
living with HIV (PLWH) and are associated with poor health outcomes. Optimizing
retention in primary care is vital, as poor retention is associated with delayed
receipt of antiretroviral (ARV) therapy, ARV non-adherence, and poor health
outcomes, including failure to suppress viral load, decreased CD4 counts, and
clinically significant ARV drug resistance. We hypothesized that MH service
utilization would be associated with improved retention in care for patients with
HIV and MH comorbidities. METHODS: This is a retrospective analysis of PLWH
initiating outpatient HIV health care at a university-affiliated HIV clinic
between January 2007 and December 2013. We examined the association between MH
service utilization and retention in care, the outcome of interest, using
univariate and multivariable logistic regression. RESULTS: Overall, 627 (84.4%)
out of 743 patients were retained in care using the Health Resources & Services
Administration HIV/AIDS Bureau (HRSA/HAB) metric. A multivariable model adjusted
for several sociodemographic factors, MH comorbidities, and MH service
utilization. The results suggest that lack of health insurance (public ORadj =
0.3, p < 0.01; no insurance ORadj = 0.4, p < 0.01) and >= 3 MH comorbidities
(ORadj = 0.3, P = 0.01) were associated with decreased retention in care.
Conversely, older age (> 45 years, ORadj. = 1.6, p = 0.14) and >= 3 MH service
utilization visits (ORadj. = 6.8, p < 0.01) were associated with increased
retention in care. CONCLUSIONS: Even in the absence of documented MH
comorbidities, improved retention in care was observed with increasing MH service
utilization. In order to achieve the US-based National HIV/AIDS Strategy goal of
90% retention in care for PLWH, MH service utilization should be considered along
with other evidence-based interventions to improve retention for PLWH newly
engaged in care.
PMID- 29338736
TI - Spatial panorama of malaria prevalence in Africa under climate change and
interventions scenarios.
AB - BACKGROUND: Malaria is highly sensitive to climatic variables and is strongly
influenced by the presence of vectors in a region that further contribute to
parasite development and sustained disease transmission. Mathematical analysis of
malaria transmission through the use and application of the value of the basic
reproduction number (R0) threshold is an important and useful tool for the
understanding of disease patterns. METHODS: Temperature dependence aspect of R0
obtained from dynamical mathematical network model was used to derive the spatial
distribution maps for malaria transmission under different climatic and
intervention scenarios. Model validation was conducted using MARA map and the
Annual Plasmodium falciparum Entomological Inoculation Rates for Africa. RESULTS:
The inclusion of the coupling between patches in dynamical model seems to have no
effects on the estimate of the optimal temperature (about 25 degrees C) for
malaria transmission. In patches environment, we were able to establish a
threshold value (about alpha = 5) representing the ratio between the migration
rates from one patch to another that has no effect on the magnitude of R0. Such
findings allow us to limit the production of the spatial distribution map of R0
to a single patch model. Future projections using temperature changes indicated a
shift in malaria transmission areas towards the southern and northern areas of
Africa and the application of the interventions scenario yielded a considerable
reduction in transmission within malaria endemic areas of the continent.
CONCLUSIONS: The approach employed here is a sole study that defined the limits
of contemporary malaria transmission, using R0 derived from a dynamical
mathematical model. It has offered a unique prospect for measuring the impacts of
interventions through simple manipulation of model parameters. Projections at
scale provide options to visualize and query the results, when linked to the
human population could potentially deliver adequate highlight on the number of
individuals at risk of malaria infection across Africa. The findings provide a
reasonable basis for understanding the fundamental effects of malaria control and
could contribute towards disease elimination, which is considered as a challenge
especially in the context of climate change.
PMID- 29338737
TI - Transcriptome profiling of whitefly guts in response to Tomato yellow leaf curl
virus infection.
AB - BACKGROUND: Plant viruses in agricultural crops are of great concern worldwide,
and over 75% of them are transmitted from infected to healthy plants by insect
vectors. Tomato yellow leaf curl virus (TYLCV) is a begomovirus, which is the
largest and most economically important group of plant viruses, transmitted by
the whitefly Bemisia tabaci. The circulation of TYLCV in the insect involves
complex insect-virus interactions, whereas the molecular mechanisms of these
interactions remain ambiguous. The insect gut as a barrier for viral entry and
dissemination is thought to regulate the vector specificity. However, due to its
tiny size, information for the responses of whitefly gut to virus infection is
limited. METHODS: We investigated the transcriptional response of the gut of B.
tabaci Middle East-Asia Minor 1 species to TYLCV infection using Illumina
sequencing. RESULTS: A total of 5207 differentially expressed genes (DEGs)
between viruliferous and non-viruliferous whitefly guts were identified.
Enrichment analyses showed that cargo receptor and ATP-binding cassette (ABC)
transporters were enriched in DEGs, and might help the virus to cross gut
barrier. TYLCV could perturb cell cycle and DNA repair as a possible result of
its replication in the whitefly. Our data also demonstrated that TYLCV can
activate whitefly defense responses, such as antimicrobial peptides. Meanwhile, a
number of genes involved in intracellular signaling were activated by TYLCV
infection. CONCLUSIONS: Our results reveal the complex insect-virus relationship
in whitefly gut and provide substantial molecular information for the role of
insect midguts in virus transmission.
PMID- 29338738
TI - Rapid HIV disease progression following superinfection in an HLA-B*27:05/B*57:01
positive transmission recipient.
AB - BACKGROUND: The factors determining differential HIV disease outcome among
individuals expressing protective HLA alleles such as HLA-B*27:05 and HLA-B*57:01
remain unknown. We here analyse two HIV-infected subjects expressing both HLA
B*27:05 and HLA-B*57:01. One subject maintained low-to-undetectable viral loads
for more than a decade of follow up. The other progressed to AIDS in < 3 years.
RESULTS: The rapid progressor was the recipient within a known transmission pair,
enabling virus sequences to be tracked from transmission. Progression was
associated with a 12% Gag sequence change and 26% Nef sequence change at the
amino acid level within 2 years. Although next generation sequencing from early
timepoints indicated that multiple CD8+ cytotoxic T lymphocyte (CTL) escape
mutants were being selected prior to superinfection, < 4% of the amino acid
changes arising from superinfection could be ascribed to CTL escape. Analysis of
an HLA-B*27:05/B*57:01 non-progressor, in contrast, demonstrated minimal virus
sequence diversification (1.1% Gag amino acid sequence change over 10 years), and
dominant HIV-specific CTL responses previously shown to be effective in control
of viraemia were maintained. Clonal sequencing demonstrated that escape variants
were generated within the non-progressor, but in many cases were not selected. In
the rapid progressor, progression occurred despite substantial reductions in
viral replicative capacity (VRC), and non-progression in the elite controller
despite relatively high VRC. CONCLUSIONS: These data are consistent with previous
studies demonstrating rapid progression in association with superinfection and
that rapid disease progression can occur despite the relatively the low VRC that
is typically observed in the setting of multiple CTL escape mutants.
PMID- 29338739
TI - Interventions for preventing or treating malnutrition in homeless problem
drinkers: a systematic review.
AB - BACKGROUND: Excessive drinking leads to poor absorption of nutrients and homeless
problem-drinkers often have nutritionally inadequate diets. Depletion of
nutrients such as vitamin B1 can lead to cognitive impairment, which can hinder
efforts to reduce drinking or engage with services. This review aimed to assess
effectiveness of interventions designed to prevent or treat malnutrition in
homeless problem-drinkers. METHODS: We systematically searched nine electronic
databases and 13 grey literature sources for studies evaluating interventions to
improve nutrition in homeless populations, without regional or language
restrictions. Screening for inclusion was done in duplicate. One reviewer
extracted data and assessed risk of bias, and another checked the extractions.
Primary outcomes were nutrition status/deficiency, liver damage, and cognitive
function. Secondary outcomes included abstinence, comorbidities, resource use,
acceptability and engagement with intervention. Results were synthesised
narratively. RESULTS: We included 25 studies (2 Randomised Controlled Trials; 15
uncontrolled before and after; 7 surveys; 1 case-control). Nine studies evaluated
educational and support interventions, five food provision, and three supplement
provision. Eight studies evaluated a combination of these interventions. No two
interventions were the same, and all studies were at high risk of bias.
Nutritional status (intake/ deficiency) were reported in 11 studies and liver
function in one. Fruit and vegetable intake improved with some education and
support interventions (n = 4 studies) but not others (n = 2). Vitamin supplements
appeared to improve vitamin deficiency levels in the blood (n = 2). Free or
subsidised meals (n = 4) and food packs (n = 1) did not always fulfil dietary
needs, but were usually considered acceptable by users. Some multicomponent
interventions improved nutrition (n = 3) but acceptability varied (n = 3). No
study reported cost effectiveness. CONCLUSIONS: The evidence for any one
intervention for improving malnutrition in homeless problem-drinkers was based on
single studies at high risk of bias. Various food and supplement provision
interventions appear effective in changing nutritional status in single studies.
Educational and multicomponent interventions show improved nutritional behaviour
in some studies but not others. Further better quality evidence is required
before these interventions can be recommended for implementation. Any future
studies should seek the end user input in their design and conduct. TRIAL
REGISTRATION: Registered with PROSPERO: CRD42015024247 .
PMID- 29338740
TI - Is sweat testing for cystic fibrosis feasible in patients with down syndrome?
AB - BACKGROUND: Recurrent airway infections are common in patients with Down's
syndrome (DS). Hence, ruling out Cystic Fibrosis (CF) in these patients is often
required. In the past, the value of sweat testing - the gold standard to diagnose
CF - has been questioned in DS as false positive results have been reported.
However, these reports are based on measurements of sweat osmolality or sodium
concentrations, not chloride concentrations. This study analyses sweat secretion
rate and chloride concentration in sweat samples of patients with DS in
comparison to healthy controls. METHODS: We assessed sweat samples in 16 patients
with DS and 16 healthy controls regarding sweat secretion rate (SSR) and sweat
chloride concentration. RESULTS: All measured chloride concentrations were within
the normal range. The chloride concentrations were slightly, but not
significantly lower in patients with DS (15,54 mmol/l (+/-4,47)) compared to
healthy controls (18,31 mmol/l (+/-10,12)). While no gender gap in chloride
concentration could be found, chloride concentration increased with age in both
groups. Insufficient sweat was collected in 2 females with DS (12.5% of the study
group) but not in an individual of the control group. A significant lower sweat
secretion rate was found in the DS group (27,6 MUl/30 min (+/- 12,18)) compared
to the control group (42,7 MUl/30 min (+/- 21,22)). In a sub-analysis, female
patients produced significantly less sweat (20,8 +/- 10,6 MUl/30 min) than male
patients with DS (36,4 +/- 7,8 MUl/30 min), which accounts for the difference
between patients and controls. Furthermore, while the sweating secretion rate
increased with age in the control group, it did not do so in the DS group. Once
again this was due to female patients with DS, who did not show a significant
increase of sweat secretion rate with age. CONCLUSIONS: Sweat chloride
concentrations were within the normal range in patients with DS and therefore
seem to be a reliable tool for testing for CF in these patients. Interestingly,
we found a reduced sweat secretion rate in the DS group. Whether the last one has
a functional and clinical counterpart, possibly due to a disturbed
thermoregulation in DS patients, requires further investigation.
PMID- 29338741
TI - Knowledge and practices of general practitioners at district hospitals towards
cervical cancer prevention in Burundi, 2015: a cross-sectional study.
AB - BACKGROUND: Well-organized screening and treatment programmes are effective to
prevent Invasive Cervical Cancer (ICC) in LMICs. To achieve this, the World
Health Organization (WHO) recommends the involvement of existing health personnel
in casu doctors, nurses, midwives in ICC prevention. A necessary precondition is
that health personnel have appropriate knowledge about ICC. Therefore, to inform
policy makers and training institutions in Burundi, we documented the knowledge
and practices of general practitioners (GPs) at district hospital level towards
ICC control. METHODS: A descriptive cross-sectional survey was conducted from
February to April, 2015 among all GPs working in government district hospitals. A
structured questionnaire and a scoring system were used to assess knowledge and
practices of GPs. RESULTS: The participation rate was 58.2%. Majority of GPs
(76.3%) had appropriate knowledge (score > 70%) on cervical cancer disease; but
some risk factors were less well known as smoking and the 2 most important
oncogenic HPV. Only 8.4% of the participants had appropriate knowledge on ICC
prevention: 55% of the participants were aware that HPV vaccination exists and
48.1% knew cryotherapy as a treatment method for CIN. Further, 15.3% was aware of
VIA as a screening method. The majority of the participants (87%) never or rarely
propose screening tests to their clients. Only 2 participants (1.5%) have already
performed VIA/VILI. Wrong thoughts were also reported: 39.7% thought that CIN
could be treated with radiotherapy; 3.1% thought that X-ray is a screening
method. CONCLUSION: In this comprehensive assessment, we observed that Burundian
GPs have a very low knowledge level about ICC prevention, screening and
treatment. Suboptimal practices and wrong thoughts related to ICC screening and
treatments have also been documented. We therefore recommend an adequate pre- and
in-service training of GPs and most probably nurses on ICC control before setting
up any public health intervention on ICC control.
PMID- 29338742
TI - M2-polarized tumor-associated macrophages facilitated migration and epithelial
mesenchymal transition of HCC cells via the TLR4/STAT3 signaling pathway.
AB - BACKGROUND: M2-polarized macrophages are tumor-associated-macrophages (TAMs),
which are important contents of tumor-infiltrating immune cells. Toll-like
receptor 4 (TLR4) is a molecular biomarker of tumor aggressiveness and poor
prognosis. Toll-like receptors (TLRs) have important roles in the immune system
and M2-polarized macrophages. However, the effects of TLR4 on M2-polarized
macrophages in hepatocellular carcinoma (HCC) are unknown. Here, TLR4 expressed
on HCC cells mediates the pro-tumor effects and mechanisms of M2-polarized
macrophages. METHODS: THP-1 cells were induced to differentiate into M2-like
macrophages through treatments with IL-4, IL-13, and phorbol myristate acetate
(PMA). We used the HCC cell lines SMMC-7721 and MHCC97-H cultured in conditioned
medium from M2-like macrophages (M2-CM) to investigate the migration potential of
HCC cells and epithelial-mesenchymal transition (EMT)-associated molecular
genetics. Signaling pathways that mediated M2-CM-promoted HCC migration were
detected using western blotting. RESULTS: HCC cells cultured with M2-CM displayed
a fibroblast-like morphology, an increased metastatic capability, and expression
of EMT markers. TLR4 expression was markedly increased in M2-CM-treated HCC
cells. TLR4 overexpression promoted HCC cell migration, and a TLR4-neutralizing
antibody markedly inhibited HCC EMT in cells cultured with M2-CM. Furthermore,
the TLR4/(signal transducer and activator of transcription 3 (STAT3) signaling
pathway contributed to the effects of M2-CM on HCC cells. CONCLUSIONS: Taken
together, M2-polarized macrophages facilitated the migration and EMT of HCC cells
via the TLR4/STAT3 signaling pathway, suggesting that TLR4 may be a novel
therapeutic target. These results improve our understanding of M2-polarized
macrophages.
PMID- 29338743
TI - The prospective and concurrent effect of exercise on health related quality of
life in older adults over a 3 year period.
AB - BACKGROUND: It is not clear whether socioeconomic status influences health
outcomes among older adults through its effect on physical activity. The aim of
this study was to assess the effect of sex and neighborhood socio-economic status
on the change in health related quality of life (HR-QOL) as a function of
physical activity over a three-year period. METHODS: This cohort study included
French-speaking community-dwelling older adults recruited in primary care
practices in the province of Quebec and participating in the 'Etude sur la Sante
des Aines' (ESA)-Services study on the health of the elderly. Primary care
practices were recruited through participating general practitioners (GPs)
working full-time in the health administrative region. A stratified sample was
comprised of various types of primary care practices (family medicine group,
local community health services centers, primary care practices with less than 3
GPs, and with at least 3 GPs). In this study sample, 967 participants with scores
>=26 on the Mini Mental State Examination (MMSE) were included and followed for 3
years to study HR-QOL as a function of reported exercise at baseline and follow
up, controlling for study variables. Analyses were also carried out to study the
effect of change in reported exercise at follow-up with respect to baseline and
categorised as follows: no change, decrease in exercise and increase in exercise.
The interaction terms area of residence socio-economic status*exercise and
sex*exercise, were tested. RESULTS: Exercise at baseline did not significantly
predict HR-QOL at follow-up when adjusting for all other study variables.
Exercise at follow-up was cross-sectionally associated with follow-up HR-QOL.
Participants reporting never exercising and those reporting a decrease in
exercise reported a lower HR-QOL at follow-up, when controlling for all other
study variables. There was no interaction between exercise and sex and
socioeconomic status. CONCLUSIONS: For healthy ageing, maintaining and increasing
physical activity throughout the years is necessary for improved HR-QOL. Past
physical activity does not confer protection against future decline of HR-QOL.
Future research should focus on potential moderating and mediating psycho-social
barriers associated with exercising in older age populations.
PMID- 29338744
TI - New insights in the relative radiobiological effectiveness of proton irradiation.
AB - BACKGROUND: Proton radiotherapy is a form of charged particle therapy that is
preferentially applied for the treatment of tumors positioned near to critical
structures due to their physical characteristics, showing an inverted depth-dose
profile. The sparing of normal tissue has additional advantages in the treatment
of pediatric patients, in whom the risk of secondary cancers and late morbidity
is significantly higher. Up to date, a fixed relative biological effectiveness
(RBE) of 1.1 is commonly implemented in treatment planning systems with protons
in order to correct the physical dose. This value of 1.1 comes from averaging the
results of numerous in vitro experiments, mostly conducted in the middle of the
spread-out Bragg peak, where RBE is relatively constant. However, the use of a
constant RBE value disregards the experimental evidence which clearly
demonstrates complex RBE dependency on dose, cell- or tissue type, linear energy
transfer and biological endpoints. In recent years, several in vitro studies
indicate variations in RBE of protons which translate to an uncertainty in the
biological effective dose delivery to the patient. Particularly for regions
surrounding the Bragg peak, the more localized pattern of energy deposition leads
to more complex DNA lesions. These RBE variations of protons bring the validity
of using a constant RBE into question. MAIN BODY: This review analyzes how RBE
depends on the dose, different biological endpoints and physical properties.
Further, this review gives an overview of the new insights based on findings made
during the last years investigating the variation of RBE with depth in the spread
out Bragg peak and the underlying differences in radiation response on the
molecular and cellular levels between proton and photon irradiation. Research
groups such as the Klinische Forschergruppe Schwerionentherapie funded by the
German Research Foundation (DFG, KFO 214) have included work on this topic and
the present manuscript highlights parts of the preclinical work and summarizes
the research activities in this context. SHORT CONCLUSION: In summary, there is
an urgent need for more coordinated in vitro and in vivo experiments that
concentrate on a realistic dose range of in clinically relevant tissues like lung
or spinal cord.
PMID- 29338745
TI - Study of correlation between wall shear stress and elasticity in atherosclerotic
carotid arteries.
AB - OBJECTIVE: This paper presents the use of the texture matching method to measure
the rabbit carotid artery elasticity value of the experimental group and control
group respectively. It compares the experimental rabbits, when they are prompted
by pathological histology to be at the period of carotid atherosclerosis fatty
streaks and fiber plaques, with the control group. METHODS: We have used
ultrasound linear array probe for scanning the rabbit carotid arteries. This
allows us to obtain the wall shear stress (WSS) and the elasticity values in the
atherosclerotic arteries. Using statistical analysis, we are able to clarify
whether the texture matching method can diagnose atherosclerosis at the early
stage. We also analyze the rabbit carotid artery elasticity and WSS values to
make sure whether there is a correlation between both. Combining the texture
matching method with the WSS quantitative analysis in the future can enable
better prediction of the occurrence and development of atherosclerosis by using
noninvasive medical imaging techniques. RESULTS: This study has confirmed that
from the 2nd to the 10th week, with the development of atherosclerosis, the
arterial WSS reduction has a negative correlation with the increasing of artery
wall elasticity, which means that as the arterial WSS decreases the arterial wall
becomes less elastic. Correlating shear stress with atherosclerosis can clarify
that WSS can be used as one of the effective parameters of early diagnosis of
atherosclerosis. CONCLUSION: In summary, we have found that the elasticity value
can reflect the degree of atherosclerosis more objectively. Therefore, by using
noninvasive imaging, the quantitative analysis of shear stress and combined with
texture matching method can assist in the early diagnosis of atherosclerosis.
PMID- 29338746
TI - Cost of diabetes mellitus in Africa: a systematic review of existing literature.
AB - BACKGROUND: There is an increasing recognition that non communicable diseases
impose large economic costs on households, societies and nations. However, not
much is known about the magnitude of diabetes expenditure in African countries
and to the best of our knowledge no systematic assessment of the literature on
diabetes costs in Africa has been conducted. The aim of this paper is to capture
the evidence on the cost of diabetes in Africa, review the methods used to
calculate costs and identify areas for future research. METHODS: A desk search
was conducted in Pubmed, Medline, Embase, and Science direct as well as through
other databases, namely Google Scholar. The following eligibility criteria were
used: peer reviewed English articles published between 2006 and 2016, articles
that reported original research findings on the cost of illness in diabetes, and
studies that covered at least one African country. Information was extracted
using two data extraction sheets and results organized in tables. Costs presented
in the studies under review are converted to 2015 international dollars prices
(I$). RESULTS: Twenty six articles are included in this review. Annual national
direct costs of diabetes differed between countries and ranged from I$3.5 billion
to I$4.5 billion per annum. Indirect costs per patient were generally higher than
the direct costs per patient of diabetes. Outpatient costs varied by study
design, data source, perspective and healthcare cost categories included in the
total costs calculation. The most commonly included healthcare items were drug
costs, followed by diagnostic costs, medical supply or disposable costs and
consultation costs. In studies that reported both drug costs and total costs,
drug costs took a significant portion of the total costs per patient. The highest
burden due to the costs associated with diabetes was reported in individuals
within the low income group. CONCLUSION: Estimation of the costs associated with
diabetes is crucial to make progress towards meeting the targets laid out in
Sustainable Development Goal 3 set for 2030. The studies included in this review
show that the presence of diabetes leads to elevated costs of treatment which
further increase in the presence of complications. The cost of drugs generally
contributed the most to total direct costs of treatment. Various methods are used
in the estimation of diabetes healthcare costs and the costs estimated between
countries differ significantly. There is room to improve transparency and make
the methodologies used standard in order to allow for cost comparisons across
studies.
PMID- 29338747
TI - Oxidative stress predicts cognitive decline with aging in healthy adults: an
observational study.
AB - BACKGROUND: Redox signaling, which can be assessed by circulating aminothiols,
reflects oxidative stress (OS) status and has been linked to clinical
cardiovascular disease and its risk factors. These, in turn, are related to
executive function decline. OS may precede the pro-inflammatory state seen in
vascular disease. The objective of this study is to investigate the association
between aminothiol markers of OS and inflammation in cognitive decline,
especially in the executive cognitive domain which is highly susceptible to
cardiovascular risk factors and is an important predictor of cognitive
disability. METHODS: The study design is that of a longitudinal cohort study
within the setting of a large academic institution with participants being
university employees (n = 511), mean age 49 years, 68% women, and 23% African
American. These participants were followed for four consecutive years with a
yearly cognitive assessment conducted using computerized versions of 15 cognitive
tests. Peripheral cystine, glutathione, their disulfide derivatives, and C
reactive protein (CRP) were measured. RESULTS: Lower levels of glutathione at
baseline was associated with a decline in the executive domain over 4 years
(covariate-adjusted relative risk (RR) for glutathione = 1.70 (95% CI = 1.02
2.85), p = 0.04). Furthermore, a longitudinal decline in glutathione level was
associated with a faster decline in the executive domain (p = 0.03). None of the
other OS markers or CRP were linked to cognitive decline over 4 years.
CONCLUSION: Increased OS reflected by decreased glutathione was associated with a
decline in executive function in a healthy population. In contrast, inflammation
was not linked to cognitive decline. OS may be an earlier biomarker that precedes
the inflammatory phase of executive decline with aging.
PMID- 29338748
TI - Finite element analysis of intramedullary nailing and double locking plate for
treating extra-articular proximal tibial fractures.
AB - BACKGROUND: Proximal tibia fractures are one of the most familiar fractures.
Surgical approaches are usually needed for anatomical reduction. However, no
single treatment method has been widely established as the standard care. Our
present study aims to compare the stress and stability of intramedullary nails
(IMN) fixation and double locking plate (DLP) fixation in the treatment of extra
articular proximal tibial fractures. METHODS: A three-dimensional (3D) finite
element model of the extra-articular proximal tibial fracture, whose 2-cm bone
gap began 7 cm from the tibial plateau articular surface, was created fixed by
different fixation implants. The axial compressive load on an adult knee during
single-limb stance was imitated by an axial force of 2500 N with a distribution
of 60% to the medial compartment, while the distal end was fixed effectively. The
equivalent von Mises stress and displacement of the model was used as the output
measures for analysis. RESULTS: The maximal equivalent von Mises stress value of
the system in the IMN model was 293.23 MPa, which was higher comparing against
that in the DLP fixation model (147.04 MPa). And the mean stress of the model in
the IMN model (9.25 MPa) was higher than that of the DLP fixation system in terms
of equivalent von Mises stress (EVMS) (P < 0.0001). The maximal value of
displacement (sum) in the IMN system was 8.82 mm, which was lower than that in
the DLP fixation system (9.48 mm). CONCLUSIONS: This study demonstrated that the
stability provided by the locking plate fixation system was superior to the
intramedullary nails fixation system and served as an alternative fixation for
the extra-articular proximal tibial fractures of young patients.
PMID- 29338749
TI - Interleukin-6 induces fat loss in cancer cachexia by promoting white adipose
tissue lipolysis and browning.
AB - BACKGROUND: Cancer cachexia is a progressive and multi-factorial metabolic
syndrome characterized by loss of adipose tissue and skeletal muscle. White
adipose tissue (WAT) lipolysis and white-to-brown transdifferentiation of WAT
(WAT browning) are proposed to contribute to WAT atrophy in cancer cachexia.
Chronic inflammation, mediated by cytokines such as tumor necrosis factor alpha
(TNF-alpha) and interleukin-6 (IL-6), has been reported to promote cancer
cachexia. However, whether chronic inflammation promotes cancer cachexia by
regulating WAT metabolism and the underlying mechanism remains unclear. METHODS:
In this study, we first analyzed the association between chronic inflammation and
WAT metabolism in gastric and colorectal cancer cachectic patients. In cachectic
mice treated with anti-IL-6 receptor antibody, we clarified whether WAT lipolysis
and browning were regulated by IL-6. RESULTS: Clinical analyses showed positive
significant association between serum IL-6 and free fatty acid (FFA) both in
early- and late-stage cancer cachexia. However, serum TNF-alpha was positively
associated with serum FFA in the early- but not late-stage cachexia. WAT
lipolysis was increased in early- and late-stage cachexia, while WAT browning was
detected only in late-stage cachexia. Anti-IL-6 receptor antibody inhibited WAT
lipolysis and browning in cachectic mice. CONCLUSIONS: Based on these findings,
we conclude that chronic inflammation (especially that mediated by IL-6) might
promote cancer cachexia by regulating WAT lipolysis in early-stage cachexia and
browning in late-stage cachexia.
PMID- 29338751
TI - Evaluation of the effects of a designated program on illegal drug cessation among
adolescents who experiment with drugs.
AB - BACKGROUND: Studies indicate that adolescent-onset drug users experience a
greater likelihood of dependence that continues into adulthood. The importance of
early intervention was evident in treating adolescents before their substance use
progressed. We examined the effectiveness of an intervention program that
prevents students who experiment with drugs from reusing them. METHODS: The study
was based on 10 out of 18 invited schools that were randomly assigned to either
the intervention group (5 schools, n = 43) or the comparison group (5 schools, n
= 41). The intervention group received an E-course program that comprised a main
intervention course (12 sessions) and a booster course (2 sessions). By reducing
the burden of teaching content during the 14 sessions, the in-class counselor had
opportunities for face-to-face discussions with students on their ambivalence
toward quitting illegal drugs. The comparison group received the conventional
didactic drug prevention course (2 sessions). Outcomes in terms of stress
management, refusal skills, pros of drug use, cons of drug use, and drug use
resistance self-efficacy were measured via structured questionnaires conducted
thrice: at baseline, after the main intervention sessions, and after the booster
sessions. A linear mixed model (LMM) was employed to investigate the effects of
time and groups on the outcome variables with group, time, and group * time as
fixed effects. Subjects and schools were selected as random effects in order to
consider both within-subject and within-school correlations. RESULTS: There was a
significant group * time interaction with regard to stress management, refusal
skills, pros of drug use, and drug use resistance self-efficacy, excluding cons
of drug use. The intervention group displayed better stress management compared
to the comparison group after the booster intervention. Similar between-group
differences were identified in that the intervention group displayed better
refusal skills and drug use resistance self-efficacy compared to that of the
comparison group. The intervention group favored using drugs less (a decrease in
the pros of drug use score) compared to the comparison group after the booster
intervention. CONCLUSIONS: Our program provided an example of the results of
early intervention among students who experiment with illegal drugs.
PMID- 29338752
TI - Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA
damage response.
AB - BACKGROUND: Viral protein R (Vpr) is an accessory protein of HIV-1, which is
potentially involved in the infection of macrophages and the induction of the
ataxia-telangiectasia and Rad3-related protein (ATR)-mediated DNA damage response
(DDR). It was recently proposed that the SLX4 complex of structure-specific
endonuclease is involved in Vpr-induced DDR, which implies that aberrant DNA
structures are responsible for this phenomenon. However, the mechanism by which
Vpr alters the DNA structures remains unclear. RESULTS: We found that Vpr unwinds
double-stranded DNA (dsDNA) and invokes the loading of RPA70, which is a single
stranded DNA-binding subunit of RPA that activates the ATR-dependent DDR. We
demonstrated that Vpr influenced RPA70 to accumulate in the corresponding region
utilizing the LacO/LacR system, in which Vpr can be tethered to the LacO locus.
Interestingly, RPA70 recruitment required chromatin remodelling via Vpr-mediated
ubiquitination of histone H2B. On the contrary, Q65R mutant of Vpr, which lacks
ubiquitination activity, was deficient in both chromatin remodelling and RPA70
loading on to the chromatin. Moreover, Vpr-induced unwinding of dsDNA
coincidently resulted in the accumulation of negatively supercoiled DNA and
covalent complexes of topoisomerase 1 and DNA, which caused DNA double-strand
breaks (DSBs) and DSB-directed integration of proviral DNA. Lastly, we noted the
dependence of Vpr-promoted HIV-1 infection in resting macrophages on
topoisomerase 1. CONCLUSIONS: The findings of this study indicate that Vpr
induced structural alteration of DNA is a primary event that triggers both DDR
and DSB, which ultimately contributes to HIV-1 infection.
PMID- 29338750
TI - Reperfusion therapy in acute ischemic stroke: dawn of a new era?
AB - Following the success of recent endovascular trials, endovascular therapy has
emerged as an exciting addition to the arsenal of clinical management of patients
with acute ischemic stroke (AIS). In this paper, we present an extensive overview
of intravenous and endovascular reperfusion strategies, recent advances in AIS
neurointervention, limitations of various treatment paradigms, and provide
insights on imaging-guided reperfusion therapies. A roadmap for imaging guided
reperfusion treatment workflow in AIS is also proposed. Both systemic
thrombolysis and endovascular treatment have been incorporated into the standard
of care in stroke therapy. Further research on advanced imaging-based approaches
to select appropriate patients, may widen the time-window for patient selection
and would contribute immensely to early thrombolytic strategies, better
recanalization rates, and improved clinical outcomes.
PMID- 29338753
TI - Examining within- and across-day relationships between transient and chronic
stress and parent food-related parenting practices in a racially/ethnically
diverse and immigrant population : Stress types and food-related parenting
practices.
AB - BACKGROUND: Although prior research suggests that stress may play a role in
parent's use of food-related parenting practices, it is unclear whether certain
types of stress (e.g., transient, chronic) result in different food-related
parenting practices. Identifying whether and how transient (i.e., momentary;
parent/child conflict) and chronic (i.e., long-term; unemployment >6 months)
sources of stress are related to parent food-related parenting practices is
important with regard to childhood obesity. This is particularly important within
racially/ethnically diverse parents who may be more likely to experience both
types of stress and who have higher levels of obesity and related health
problems. The current study examined the association between transient and
chronic stressors and food-related parenting practices in a racially/ethnically
diverse and immigrant sample. METHODS: The current study is a cross-sectional,
mixed-methods study using ecological momentary assessment (EMA). Parents (mean
age = 35; 95% mothers) of children ages 5-7 years old (n = 61) from six
racial/ethnic groups (African American, American Indian, Hispanic, Hmong, Somali,
White) participated in this ten-day in-home observation with families. RESULTS:
Transient stressors, specifically interpersonal conflicts, had significant within
day effects on engaging in more unhealthful food-related parenting practices the
same evening with across-day effects weakening by day three. In contrast,
financial transient stressors had stronger across-day effects. Chronic stressors,
including stressful life events were not consistently associated with more
unhealthful food-related parenting practices. CONCLUSIONS: Transient sources of
stress were significantly associated with food-related parenting practices in
racially/ethnically diverse and immigrant households. Chronic stressors were not
consistently associated with food-related parenting practices. Future research
and interventions may want to assess for transient sources of stress in parents
and target these momentary factors in order to promote healthful food-related
parenting practices.
PMID- 29338755
TI - Hyperhomocysteinemia in bilateral anterior ischemic optic neuropathy after
conventional coronary artery bypass graft: a case report.
AB - BACKGROUND: The incidence of anterior ischemic optic neuropathy after coronary
artery bypass graft procedures ranges from 1.3 to 0.25%. The mechanisms of
anterior ischemic optic neuropathy after cardiovascular procedures remain
undefined but many systemic and related-to-surgery risk factors could underlie
anterior ischemic optic neuropathy. In this case, we report a rare presentation
of a bilateral anterior ischemic optic neuropathy after coronary artery bypass
graft and speculate on the preoperative hyperhomocysteinemia as an independent
risk factor for anterior ischemic optic neuropathy. CASE PRESENTATION: A 56-year
old white man, a tobacco smoker with type 2 diabetes and coronary artery disease,
underwent a conventional coronary artery bypass graft with extracorporeal
circulation. In spite of ongoing anti-aggregation, antithrombotic, and
vasodilator therapy, 10 days after the surgery he complained of severe bilateral
visual loss. Funduscopy and fluorescein angiography revealed a bilateral anterior
ischemic optic neuropathy. Analysis of preoperative laboratory tests revealed
hyperhomocysteinemia. CONCLUSION: Hyperhomocysteinemia could increase the risk of
ocular vascular damage and bilateral ocular involvement in patients who have
undergone conventional coronary artery bypass graft.
PMID- 29338754
TI - Molecular and functional signatures in a novel Alzheimer's disease mouse model
assessed by quantitative proteomics.
AB - BACKGROUND: Alzheimer's disease (AD), the most common neurodegenerative disorder,
is characterized by the deposition of extracellular amyloid plaques and
intracellular neurofibrillary tangles. To understand the pathological mechanisms
underlying AD, developing animal models that completely encompass the main
features of AD pathologies is indispensable. Although mouse models that display
pathological hallmarks of AD (amyloid plaques, neurofibrillary tangles, or both)
have been developed and investigated, a systematic approach for understanding the
molecular characteristics of AD mouse models is lacking. METHODS: To elucidate
the mechanisms underlying the contribution of amyloid beta (Abeta) and tau in AD
pathogenesis, we herein generated a novel animal model of AD, namely the AD-like
pathology with amyloid and neurofibrillary tangles (ADLPAPT) mice. The ADLPAPT
mice carry three human transgenes, including amyloid precursor protein,
presenilin-1, and tau, with six mutations. To characterize the molecular and
functional signatures of AD in ADLPAPT mice, we analyzed the hippocampal proteome
and performed comparisons with individual-pathology transgenic mice (i.e.,
amyloid or neurofibrillary tangles) and wild-type mice using quantitative
proteomics with 10-plex tandem mass tag. RESULTS: The ADLPAPT mice exhibited
accelerated neurofibrillary tangle formation in addition to amyloid plaques,
neuronal loss in the CA1 area, and memory deficit at an early age. In addition,
our proteomic analysis identified nearly 10,000 protein groups, which enabled the
identification of hundreds of differentially expressed proteins (DEPs) in ADLPAPT
mice. Bioinformatics analysis of DEPs revealed that ADLPAPT mice experienced age
dependent active immune responses and synaptic dysfunctions. CONCLUSIONS: Our
study is the first to compare and describe the proteomic characteristics in
amyloid and neurofibrillary tangle pathologies using isobaric label-based
quantitative proteomics. Furthermore, we analyzed the hippocampal proteome of the
newly developed ADLPAPT model mice to investigate how both Abeta and tau
pathologies regulate the hippocampal proteome. Because the ADLPAPT mouse model
recapitulates the main features of AD pathogenesis, the proteomic data derived
from its hippocampus has significant utility as a novel resource for the research
on the Abeta-tau axis and pathophysiological changes in vivo.
PMID- 29338757
TI - A rapid high-resolution method for resolving DNA topoisomers.
AB - OBJECTIVE: Agarose gel electrophoresis has been the mainstay technique for the
analysis of DNA samples of moderate size. In addition to separating linear DNA
molecules, it can also resolve different topological forms of plasmid DNAs, an
application useful for the analysis of the reactions of DNA topoisomerases.
However, gel electrophoresis is an intrinsically low-throughput technique and
suffers from other potential disadvantages. We describe the application of the
QIAxcel Advanced System, a high-throughput capillary electrophoresis system, to
separate DNA topoisomers, and compare this technique with gel electrophoresis.
RESULTS: We prepared a range of topoisomers of plasmids pBR322 and pUC19, and a
339 bp DNA minicircle, and compared their separation by gel electrophoresis and
the QIAxcel System. We found superior resolution with the QIAxcel System, and
that quantitative analysis of topoisomer distributions was straightforward. We
show that the QIAxcel system has advantages in terms of speed, resolution and
cost, and can be applied to DNA circles of various sizes. It can readily be
adapted for use in compound screening against topoisomerase targets.
PMID- 29338756
TI - Spatial access to restaurants and grocery stores in relation to frequency of home
cooking.
AB - BACKGROUND: Little is known about the relation between the neighbourhood food
environment and home cooking. We explored the independent and combined
associations between residential neighbourhood spatial access to restaurants and
grocery stores with home cooking in European adults. METHODS: Data of 5076
participants of the SPOTLIGHT study were collected across five European countries
in 2014. Food retailers were classified into grocery stores (supermarkets and
local food shops) and restaurants (full-service restaurants, fast food and take
away restaurants, cafe/bars). We used multinomial logistic regression models to
test the associations between tertiles of spatial access to restaurants and
spatial to access grocery stores and the outcome 'frequency of home cooking'
categorized into 0-3; 4-5; and 6-7 days/week. Additive interaction analysis was
used to test the combined association between access to grocery stores and to
restaurants with home cooking. RESULTS: Mean age was 52.3 years; most
participants were women (55.5%) and completed higher education (53.8%). Residents
with highest access to restaurants had a reduced likelihood of home cooking 6-7
days/week (vs. 0-3 days/week) (relative risk ratio (RRR) 0.42; 95%CI = 0.23-0.76)
when compared with lowest access to restaurants. No association was found for
spatial access to grocery stores. Additive interaction analysis showed that
individuals with medium access to grocery stores and highest access to
restaurants had the lowest likelihood (RRR = 0.29, 95%CI = 0.10-0.84) of cooking
6-7 days/week when compared to individuals with lowest access to restaurants and
highest access to grocery stores. CONCLUSION: Greater neighbourhood spatial
access to restaurants was associated with lower frequency of home cooking,
largely independent of access to grocery stores.
PMID- 29338758
TI - Vitamin D status and dental caries in healthy Swedish children.
AB - Background: Vitamin D is crucial for mineralized tissue formation and
immunological functions. The purpose of this study was to evaluate the
association between vitamin D status and dental status in healthy children with
vitamin D supplementation in infancy and at 6 years of age. Method: Eight-year
old children who had participated in a vitamin D intervention project when they
were 6 years old were invited to participate in a dental follow-up study. They
had fair or darker skin complexion and represented two geographically distant
parts of Sweden. 25-hydroxy vitamin D in serum had been measured at 6 years of
age and after a 3-month intervention with 25, 10 or 2 (placebo) MUg of vitamin
D3 per day. Two years later, caries and enamel defects
were scored, self-reported information on e.g., oral behavior, dietary habits and
intake of vitamin D supplements was collected, and innate immunity peptide LL37
levels in saliva and cariogenic mutant streptococci in tooth biofilm were
analyzed. The outcome variables were caries and tooth enamel defects. Results:
Dental status was evaluated in 85 of the 206 children in the basic intervention
study. Low vitamin D levels were found in 28% at baseline compared to 11% after
the intervention, and 34% reported continued intake of vitamin D supplements.
Logistic regression supported a weak inverse association between vitamin D status
at 6 years of age and caries 2 years later (odds ratio 0.96; p = 0.024) with
minor attenuation after an adjustment for potential confounders. Multivariate
projection regression confirmed that insufficient vitamin D levels correlated
with caries and higher vitamin D levels correlated with being caries-free.
Vitamin D status at 6 years of age was unrelated to enamel defects but was
positively associated with saliva LL37 levels. Conclusion: An association between
vitamin D status and caries was supported, but it was not completely consistent.
Vitamin D status at 6 years of age was unrelated to enamel defects but was
positively associated with LL37 expression. Trial registration: The basic
intervention study was registered at ClinicalTrials.gov with register number
NCT01741324 www.clinicaltrials.gov/ct2/show/NCT02347293 on November 26, 2012.
PMID- 29338759
TI - Correction to: Avoidable waste related to inadequate methods and incomplete
reporting of interventions: a systematic review of randomized trials performed in
Sub-Saharan Africa.
AB - CORRECTION: In the original publication [1] the last sentence in the last
paragraph under 'Perspectives and implications' in the Discussions section needs
to be removed. The correct version can be found in this Erratum.
PMID- 29338760
TI - Increased Plasmodium chabaudi malaria mortality in mice with nutritional iron
deficiency can be reduced by short-term adjunctive iron supplementation.
AB - BACKGROUND: Iron deficiency is the most widespread nutrient deficiency and an
important cause of developmental impairment in children. However, some studies
have indicated that iron deficiency can also protect against malaria, which is a
leading cause of childhood morbidity and mortality in large parts of the world.
This has rendered interventions against iron deficiency in malaria-endemic areas
controversial. METHODS: The effect of nutritional iron deficiency on the clinical
outcome of Plasmodium chabaudi AS infection in A/J mice and the impact of
intravenous iron supplementation with ferric carboxymaltose were studied before
and after parasite infection. Plasma levels of the iron status markers hepcidin
and fibroblast growth factor 23 were measured in animals surviving and succumbing
to malaria, and accompanying tissue pathology in the liver and the spleen was
assessed. RESULTS: Nutritional iron deficiency was associated with increased
mortality from P. chabaudi malaria. This increased mortality could be partially
offset by carefully timed, short-duration adjunctive iron supplementation.
Moribund animals were characterized by low levels of hepcidin and high levels of
fibroblast growth factor 23. All infected mice had extramedullary splenic
haematopoiesis, and iron-supplemented mice had visually detectable intracellular
iron stores. CONCLUSIONS: Blood transfusions are the only currently available
means to correct severe anaemia in children with malaria. The potential of
carefully timed, short-duration adjunctive iron supplementation as a safe
alternative should be considered.
PMID- 29338761
TI - Is total femoral replacement for non-oncologic and oncologic indications a safe
procedure in limb preservation surgery? A single center experience of 22 cases.
AB - BACKGROUND: Several surgical options for the reconstruction of massive bone
defects have been described and include biologic methods with autografts and
allografts, and the use of tumor endoprostheses (total femoral replacement, TFR).
Several types of modular TFR are available, but nevertheless unpredictable
outcomes and high complication rates have been described from most authors. The
present study aims to compare results after TFR performed with modular total
femur prosthesis MML (Fa. ESKA/Orthodynamics) in patients with and without
malignant disease. METHODS: Retrospective chart review and functional
investigation (Musculoskeletal Tumor Society (MSTS) score, Harris Hip Score
(HHS), Oxford Knee Score (OKS), SF-12 Health Survey, and failure classification
according to Henderson) of TFR cases from 1995 to 2011. Indications for TFR were
malignant tumor resection from the femur (n = 9, Group A) or failure of a
revision arthroplasty without history of malignant disease (n = 13, Group B).
RESULTS: Thirty-six patients were treated during the study period, of whom 22
could be investigated clinically after a mean follow-up of 63 months. Overall
failure rate for TFR was 59.1%, leading to 38 surgical revisions. The most common
failure mechanisms were Type I (soft tissue), followed by Type IV (infection) and
Type III (mechanical failure). Mean MSTS score out of 30 was 13 (range 1-25),
with significantly higher scores in Group A (mean 19, range 3-25) than Group B
(mean 9, range 1-15). CONCLUSION: TFR is an established procedure to restore
femoral integrity. However, complication rates are considerably high, and depend
mainly on the age at initial reconstruction.
PMID- 29338762
TI - Predictors of remission with etanercept-methotrexate induction therapy and loss
of remission with etanercept maintenance, reduction, or withdrawal in moderately
active rheumatoid arthritis: results of the PRESERVE trial.
AB - BACKGROUND: The aim was to analyze characteristics that predict remission
induction and subsequent loss of remission in patients with moderately active
rheumatoid arthritis (RA) who received full-dose combination etanercept plus
methotrexate induction therapy followed by reduced-dose etanercept or etanercept
withdrawal. METHODS: Patients with Disease Activity Score based on 28-joint count
(DAS28) >3.2 and <=5.1 received open-label etanercept 50 mg once weekly (QW) plus
methotrexate for 36 weeks. Those who achieved DAS28 low disease activity by 36
weeks were randomized to double-blind treatment with etanercept 50 mg or 25 mg QW
plus methotrexate or placebo plus methotrexate for 52 weeks. All analyses were
adjusted for the continuous baseline variables of their respective remission
outcomes. RESULTS: Younger age, body mass index (BMI) <30 kg/m2, and lower Health
Assessment Questionnaire (HAQ) score at baseline were significant predictors of
week-36 remission (P < 0.05) based on DAS28, Simplified Disease Activity Index
(SDAI), and Clinical Disease Activity Index (CDAI). Baseline DAS28, SDAI, and
CDAI were significantly predictive of all three remission endpoints (P < 0.05).
For all three treatments, the strongest predictors of loss of DAS28 remission
included failure to achieve sustained remission (DAS28 < 2.6 at weeks 12, 20, 28,
and 36) with induction therapy, higher DAS28/SDAI/CDAI at randomization and at 1
month, increase in DAS28/SDAI/CDAI at 1 month, and increase in DAS28/CDAI/SDAI
components and patient-reported outcomes (PROs) at 1 month. With the exception of
not achieving sustained remission, very similar significant predictors were
observed for loss of SDAI and CDAI remission. CONCLUSION: These findings suggest
that patients with moderately active RA who are younger and have lower BMI, lower
HAQ, and lower disease activity at baseline are most likely to achieve remission
when receiving combination etanercept and methotrexate induction therapy. In
addition, patients who fail to achieve sustained remission with induction therapy
and those with worse disease activity and PROs at early time points after
initiating maintenance therapy with a full-dose or reduced-dose etanercept
methotrexate regimen or methotrexate monotherapy are most likely to lose
remission across all treatment arms. These findings may help guide clinicians'
decision-making as they treat patients to remission and beyond. TRIAL
REGISTRATION: ClinicalTrials.gov, NCT00565409 . Registered on 28 November 2007.
PMID- 29338763
TI - Sero-prevalence of HBsAg in naive HIV-infected patients in a rural locality of
Cameroon.
AB - OBJECTIVE: This study was performed in order to fill the gap of knowledge
regarding sero-epidemiology of hepatitis B virus (HBV) amongst Human
Immunodeficiency virus (HIV)-infected patients and to assess the risk factors
associated with HBV co-infection in a rural locality of Cameroon. A retrospective
and cross-sectional study was carried out from January 2008 to April 2014 within
the Mfou District Hospital. Naive HIV-infected patients were enrolled in the
study and tested for hepatitis B surface antigen (HBsAg). Preliminary pre
therapeutic data essential for follow-up was collected from the participants.
RESULTS: Overall, the sample size was constituted of 712 HIV-infected patients.
The prevalence of HBsAg was 8.99%. A significant difference was observed in the
proportion of HBsAg positive subjects with respect to the year of inclusion;
higher proportions were observed between 2011 and 2014 (P-value = 0.007).
Majority of HBV co-infected participants had severe immuno-suppression with CD4
counts lower than 100 cells/uL as compared to HIV mono-infected population but
the difference was not statistically significant. Our results confirm the high
prevalence for HBV infection among HIV-infected patients in the Mfou District
Hospital. These findings will enable stake holders to be better armed in the
elimination of viral hepatitis as a public health problem.
PMID- 29338765
TI - Infantile hypertrophic pyloric stenosis: a 4-year experience from two tertiary
care centres in Cameroon.
AB - OBJECTIVE: This study aimed to describe the clinical characteristics of patients
with infantile hypertrophic stenosis, management and its outcome in two tertiary
care centres in Cameroon. RESULTS: A total of 21 patients were included from the
two centres. The mean age at presentation was 5.2 +/- 1.2 weeks, predominantly
male with a male-to-female ratio of 4.25:1. The triad of vomiting, visible
peristalsis and palpable mass was present in only 7 (33.3%) of the participants.
The diagnosis was confirmed with ultrasounds in all participants. Ramstedt
pyloromyotomy was done in all participants and in 9.5% of the participants it was
complicated by intra-operative duodenal perforation whereas in the postoperative
period the most common complications were vomiting (6, 28.6%), sepsis (2, 9.5%),
and paralytic ileus (2, 9.5%). The mortality rate from the series is 9.5%.
According to univariate logistic regression: severe dehydration [OR = 5.41, 95%
CI = (3.11-6.97), p = 0.002], hypokalaemia [OR = 2.63, 95% CI = (1.02-5.91), p =
0.042] and surgical site infection [OR = 3.12, 95% CI (1.22-5.64), p = 0.023]
were the main predictors of mortality whereas postoperative hospital length of
stay > 5 days was significantly associated with surgical site infection [OR =
2.44, 95% CI = (1.12-6.44), p = 0.002] and postoperative nausea and vomiting [OR
= 3.64, 95% CI = (1.18-6.64), p = 0.022].
PMID- 29338764
TI - Cropping practices manipulate abundance patterns of root and soil microbiome
members paving the way to smart farming.
AB - BACKGROUND: Harnessing beneficial microbes presents a promising strategy to
optimize plant growth and agricultural sustainability. Little is known to which
extent and how specifically soil and plant microbiomes can be manipulated through
different cropping practices. Here, we investigated soil and wheat root microbial
communities in a cropping system experiment consisting of conventional and
organic managements, both with different tillage intensities. RESULTS: While
microbial richness was marginally affected, we found pronounced cropping effects
on community composition, which were specific for the respective microbiomes.
Soil bacterial communities were primarily structured by tillage, whereas soil
fungal communities responded mainly to management type with additional effects by
tillage. In roots, management type was also the driving factor for bacteria but
not for fungi, which were generally determined by changes in tillage intensity.
To quantify an "effect size" for microbiota manipulation, we found that about 10%
of variation in microbial communities was explained by the tested cropping
practices. Cropping sensitive microbes were taxonomically diverse, and they
responded in guilds of taxa to the specific practices. These microbes also
included frequent community members or members co-occurring with many other
microbes in the community, suggesting that cropping practices may allow
manipulation of influential community members. CONCLUSIONS: Understanding the
abundance patterns of cropping sensitive microbes presents the basis towards
developing microbiota management strategies for smart farming. For future
targeted microbiota management-e.g., to foster certain microbes with specific
agricultural practices-a next step will be to identify the functional traits of
the cropping sensitive microbes.
PMID- 29338766
TI - Identification of differentially expressed genes and pathways for intramuscular
fat metabolism between breast and thigh tissues of chickens.
AB - BACKGROUND: Intramuscular fat (IMF) is one of the important factors influencing
meat quality, however, for chickens, the molecular regulatory mechanisms
underlying this trait have not yet been clear. In this study, a systematic
identification of differentially expressed genes (DEGs) and molecular regulatory
mechanism related to IMF metabolism between Beijing-you chicken breast and thigh
at 42 and 90 days of age was performed. RESULTS: IMF contents, Gene Ontology (GO)
terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed,
The results showed that both IMF contents in breast at 42 and 90 d were
significantly lower (P < 0.05 or P < 0.01) than those in thigh. By microarray,
515 common known DEGs and 36 DEGs related to IMF metabolism were identified
between the breast and thigh at 42 and 90 d. Compared to thigh, the expression
levels of PPARG had significantly down-regulated (P < 0.01) in breast, but the
expression levels of RXRA and CEBPB had significantly up-regulated (P < 0.01).
However, the expression levels of LPL, FABP4, THRSP, RBP7, LDLR, FABP3, CPT2 and
PPARGC1A had significantly down-regulated in breast (P < 0.01), supporting that
PPARG and its down-stream genes had the important regulatory function to IMF
deposition. In addition, based on of DEGs, KEGG analysis revealed that PPAR
signaling pathway and cell junction-related pathways (focal adhesion and ECM
receptor interaction, which play a prominent role in maintaining the integrity of
tissues), might contribute to the IMF metabolism in chicken. CONCLUSIONS: Our
data had screened the potential candidate genes associated with chicken IMF
metabolism, and imply that IMF metabolism in chicken is regulated and mediated
not only by related functional genes and PPAR pathway, but also by others
involved in cell junctions. These findings establish the groundwork and provide
new clues for deciphering the molecular mechanisms underlying IMF deposition in
poultry. Further studies at the translational and posttranslational level are now
required to validate the genes and pathways identified here.
PMID- 29338767
TI - Effect of exercise versus cognitive behavioural therapy or no intervention on
anxiety, depression, fitness and quality of life in adults with previous
methamphetamine dependency: a systematic review.
AB - BACKGROUND: Methamphetamine (MA) is a highly addictive psychostimulant used by
approximately 52 million people worldwide. Chronic MA abuse leads to detrimental
physiological and neurological changes, as well as increases in anxiety and
depression, and decreases in overall fitness and quality of life. Exercise has
been reported to possibly reverse physiological and neurological damage caused by
previous MA use, and to reduce anxiety and depression in this population. The aim
of this systematic review was to identify, clinically appraise and synthesise the
available evidence for the effectiveness of exercise, compared to cognitive
behavioural therapy (CBT), standard care or no intervention, on decreasing
anxiety and depression and improving fitness and quality of life in previous MA
users. METHODS: Seven computerised databases were searched from inception to May
2017, namely Scopus, Cochrane Library, PubMed/MEDLINE, PEDro, CINAHL, and
ScienceDirect. Search terms included exercise, methamphetamine, fitness measures,
depression, anxiety and quality of life. Randomised and non-randomised controlled
or clinical trials and pilot studies, published in English, were considered for
inclusion. Methodological quality was critically appraised according to the PEDro
scale. Heterogeneity across studies regarding control groups and assessment
intervals rendered meta analyses inappropriate for this review and results were
thus described narratively using text and tables. RESULTS: Two hundred and fifty
one titles were identified following the initial search, and 14 potentially
relevant titles were selected and the abstracts reviewed. Three studies (two
randomised controlled trials and one quasi-experimental pilot) were included,
with an average PEDro score of 6.66. Exercise resulted in significantly lower
depression and anxiety scores versus CBT (p = 0.001). Balance also significantly
improved following exercise versus standard care (p < 0.001); as did vital
capacity, hand-grip and one-leg stand with eyes closed. There were significant
changes in all subdivisions of the Quality of Life Scale Questionnaire (p <
0.05), except psychology (p = 0.227). CONCLUSIONS: Level II evidence suggests
that exercise is effective in reducing anxiety and depression and improving
fitness in previous MA users, and Level III-2 evidence suggests that exercise is
beneficial for improving quality of life in this population. Overall recovery in
previous MA dependents might be significantly enhanced by including exercise in
the rehabilitation process. Further research is required to strengthen these
conclusions and to inform policy and health systems effectively.
PMID- 29338769
TI - Publication rate of abstracts presented at Japan Geriatrics Society Annual
Meetings (2011-2012): a retrospective observational study.
AB - OBJECTIVE: We aimed to determine the publication rate of abstracts presented at
Japan Geriatrics Society Annual Meetings. Publication rates were determined by
searching for full-text publications up to September 2017 in the MEDLINE
database. Factors associated with publication were determined. RESULTS: In total,
618 abstracts presented at Japan Geriatrics Society Annual Meetings (2011-2012)
were included. Of those, 146 (23.6% [95% CI 20.3-27.0%]) were published in peer
reviewed journals indexed in MEDLINE. The median time to publication was 13.0
months (interquartile range 6.0-25.8 months). More than 90% were published within
4 years. The publications appeared in 64 different journals, and 87.0% were
published in English-language journals. Multivariable analysis revealed more
frequent publication of oral presentations (25.4% vs 16.9% of poster
presentations; adjusted OR 1.79 [95% CI 1.05-3.06]), randomized controlled trials
(66.7% vs 22.8% for other study designs; adjusted OR 10.79 [95% CI 3.02-38.53])
and studies with n >= 100 (28.7% vs 18.4% of studies with n < 100; adjusted OR
1.97 [95% CI 1.32-2.95]). Because more than three-fourths of the abstracts
presented at Japan Geriatrics Society Annual Meetings remained unpublished within
5 years after the conferences, additional efforts may be needed to promote their
publication.
PMID- 29338768
TI - Binary-blend fibber-based capture assay of circulating tumor cells for clinical
diagnosis of colorectal cancer.
AB - BACKGROUND: In addition to conventional approaches, detecting and characterizing
CTCs in patient blood allows for early diagnosis of cancer metastasis. METHODS:
We blended poly(ethylene oxide) (PEO) into nylon-6 through electrospinning to
generate a fibrous matbased circulating tumour cells (CTCs) assay. The contents
of nylon-6 and PEO in the electrospun blend fibrous mats (EBFMs) were optimized
to facilitate high cell-substrate affinity and low leukocyte adsorption. RESULTS:
Compared with the IsoFlux System, a commercial instrument for CTC detection, the
CTC assay of EBFMs exhibited lower false positive readings and high sensitivity
and selectivity with preclinical specimens. Furthermore, we examined the clinical
diagnosis accuracy of colorectal cancer, using the CTC assay and compared the
results with those identified through pathological analyses of biopsies from
colonoscopies. Our positive expressions of colorectal cancer through CTC
detection completely matched those recognized through the pathological analyses
for the individuals having stage II, III, and IV colorectal cancer. Nevertheless,
two in four individuals having stage I colorectal cancer, recognized through
pathological analysis of biopsies from colonoscopies, exhibited positive
expression of CTCs. Ten individuals were identified through pathological analysis
as having no colorectal tumours. Nevertheless, two of these ten individuals
exhibited positive expression of CTCs. CONCLUSIONS: Thus, in this population, the
low cost EBFMs exhibited considerable capture efficiency for the non-invasive
diagnosis of colorectal cancer.
PMID- 29338770
TI - Nonmedical prescription opioid use and illegal drug use: initiation trajectory
and related risks among people who use illegal drugs in Vancouver, Canada.
AB - OBJECTIVE: We investigated the prevalence of and risk factors associated with
initiating nonmedical prescription opioid use (NMPOU) before and after illegal
drugs using data from two linked cohort studies of street youth and adults who
use illegal drugs in Vancouver, Canada. All participants who attended a study
visit between 2013 and 2016 were eligible for the primary analyses. RESULTS:
Among 512 youth and 833 adult participants, the prevalence of NMPOU was extremely
high (88% among street youth; 90% among adults), and over one-third of those who
reported engaging in NMPOU had initiated NMPOU before illegal drug use (vs.
transitioning from illegal drugs to NMPOU). Participants who reported either
transitioning to or from NMPOU had higher risk profiles, particularly related to
substance use, when compared with those who reported never engaging in NMPOU. Sub
analyses restricted to only those who engaged in NMPOU found few statistically
significant differences between those who initiated NMPOU prior to illegal drugs
versus those who initiated illegal drugs prior to NMPOU. Findings suggest that
among people who use illegal drugs, early NMPOU trajectories do not appear to
critically shape future patterns and practices.
PMID- 29338771
TI - Regulation of aquaporins in plants under stress.
AB - Aquaporins (AQP) are channel proteins belonging to the Major Intrinsic Protein
(MIP) superfamily that play an important role in plant water relations. The main
role of aquaporins in plants is transport of water and other small neutral
molecules across cellular biological membranes. AQPs have remarkable features to
provide an efficient and often, specific water flow and enable them to transport
water into and out of the cells along the water potential gradient. Plant AQPs
are classified into five main subfamilies including the plasma membrane intrinsic
proteins (PIPs), tonoplast intrinsic proteins (TIPs), nodulin 26 like intrinsic
proteins (NIPs), small basic intrinsic proteins (SIPs) and X intrinsic proteins
(XIPs). AQPs are localized in the cell membranes and are found in all living
cells. However, most of the AQPs that have been described in plants are localized
to the tonoplast and plasma membranes. Regulation of AQP activity and gene
expression, are also considered as a part of the adaptation mechanisms to stress
conditions and rely on complex processes and signaling pathways as well as
complex transcriptional, translational and posttranscriptional factors. Gating of
AQPs through different mechanisms, such as phosphorylation, tetramerization, pH,
cations, reactive oxygen species, phytohormones and other chemical agents, may
play a key role in plant responses to environmental stresses by maintaining the
uptake and movement of water in the plant body.
PMID- 29338772
TI - Incidence, risk factors and impact of protocolised care on exposure keratopathy
in critically ill adults: a two-phase prospective cohort study.
AB - BACKGROUND: Exposure keratopathy (EK) has a high incidence in critically ill
patients. We aimed to determine the rate of EK in patients admitted to our
intensive care unit (ICU), identify risk factors for developing EK and ascertain
the effectiveness of a protocol to prevent EK. METHODS: We undertook a two-phase
prospective cohort single-centre study in a general adult ICU. The first phase of
the study was observational. In the second phase of the study an eye care
protocol was introduced. Daily ophthalmic assessment was carried out using a
portable slit lamp. We also recorded Acute Physiology and Chronic Health
Evaluation II score, daily Sequential Organ Failure Assessment score, mechanical
ventilation, Richmond Agitation-Sedation Scale, and level of eye care. Student's
t test and chi 2 statistics were used for simple analysis of continuous data and
categorical data, respectively. Binary logistic regression was used to analyse
the relationship between EK (yes/no), as the dependent variable, and multiple
independent variables, calculating unadjusted and adjusted odds ratios. RESULTS:
We studied 371 patients. In the first phase, the overall rate of EK was 21% but
the rate in mechanically ventilated patients was 56%; chi 2 (1, N = 257) = 80.8,
p < 0.001. Adjusted odds ratios (AOR) for development of EK were 28.6 (8.19
43.37), 13.0 (3.16-54.38) and 1.2 (1.03-1.33) with incomplete eye closure,
mechanical ventilation, and higher SOFA score, respectively. Following the
introduction of the protocol in the second phase, the overall rate of EK reduced
to 2.6% (three cases); chi 2 (1, N = 371) = 18.6, p < 0.001. Compliance with the
protocol was 97%. CONCLUSIONS: EK is common in critically ill patients, and is
associated with mechanical ventilation and incomplete eye closure. A simple
protocol substantially reduces the incidence of EK and is easily achieved in
clinical practice.
PMID- 29338773
TI - Chemokine ligand-receptor interactions critically regulate cutaneous wound
healing.
AB - BACKGROUND: Wound healing represents a dynamic process involving directional
migration of different cell types. Chemokines, a family of chemoattractive
proteins, have been suggested to be key players in cell-to-cell communication and
essential for directed migration of structural cells. Today, the role of the
chemokine network in cutaneous wound healing is not fully understood. Unraveling
the chemokine-driven communication pathways in this complex process could
possibly lead to new therapeutic strategies in wound healing disorders. METHODS:
We performed a systematic, comprehensive time-course analysis of the expression
and function of a broad variety of cytokines, growth factors, adhesion molecules,
matrixmetalloproteinases and chemokines in a murine cutaneous wound healing
model. RESULTS: Strikingly, chemokines were found to be among the most highly
regulated genes and their expression was found to coincide with the expression of
their matching receptors. Accordingly, we could show that resting and activated
human primary keratinocytes (CCR3, CCR4, CCR6, CXCR1, CXCR3), dermal fibroblasts
(CCR3, CCR4, CCR10) and dermal microvascular endothelial cells (CCR3, CCR4, CCR6,
CCR8, CCR9, CCR10, CXCR1, CXCR2, CXCR3) express a distinct and functionally
active repertoire of chemokine receptors. Furthermore, chemokine ligand-receptor
interactions markedly improved the wound repair of structural skin cells in
vitro. CONCLUSION: Taken together, we here present the most comprehensive
analysis of mediators critically involved in acute cutaneous wound healing. Our
findings suggest therapeutic approaches for the management of wound closure by
targeting the chemokine network.
PMID- 29338774
TI - Depressive symptoms are associated with poor glycemic control among women with
type 2 diabetes mellitus.
AB - OBJECTIVE: In patients with type 2 diabetes mellitus, depressive symptoms may be
associated with metabolic deterioration. The impact of sex on this association is
unclear. The aim of this study is to analyze the relationship between depression
and metabolic control by sex. The data presented is the side product of the
clinical investigation by Rui Duarte, MD, Treatment Response in Type 2 Diabetes
Patients with Major Depression from 2007. RESULTS: A sample of 628 outpatients
with type 2 diabetes mellitus was taken from a specialized diabetes outpatient
clinic. In a univariate analysis: women's glycohemoglobin mean levels were 8.99%
whereas men's were 8.41% and the difference was statistically significant. The
proportion of women (34.3%) with pathological levels of depression (Hospital
Anxiety Depression Scale score >= 8) was significantly higher than men's (15.2%).
A linear regression analysis performed by sex and controlling for demographic,
clinical and psychological variables, showed poorer metabolic control in women
with depressive symptoms. No association was observed in men. These results
support depression as a predictor for poor metabolic control in women and the
need for detecting depressive symptoms when glycemic levels deteriorate.
PMID- 29338775
TI - Comparison of speckle-tracking echocardiography with invasive hemodynamics for
the detection of characteristic cardiac dysfunction in type-1 and type-2 diabetic
rat models.
AB - BACKGROUND: Measurement of systolic and diastolic function in animal models is
challenging by conventional non-invasive methods. Therefore, we aimed at
comparing speckle-tracking echocardiography (STE)-derived parameters to the
indices of left ventricular (LV) pressure-volume (PV) analysis to detect cardiac
dysfunction in rat models of type-1 (T1DM) and type-2 (T2DM) diabetes mellitus.
METHODS: Rat models of T1DM (induced by 60 mg/kg streptozotocin, n = 8) and T2DM
(32-week-old Zucker Diabetic Fatty rats, n = 7) and corresponding control animals
(n = 5 and n = 8, respectively) were compared. Echocardiography and LV PV
analysis were performed. LV short-axis recordings were used for STE analysis.
Global circumferential strain, peak strain rate values in systole (SrS),
isovolumic relaxation (SrIVR) and early diastole (SrE) were measured. LV
contractility, active relaxation and stiffness were measured by PV analysis.
RESULTS: In T1DM, contractility and active relaxation were deteriorated to a
greater extent compared to T2DM. In contrast, diastolic stiffness was impaired in
T2DM. Correspondingly, STE described more severe systolic dysfunction in T1DM.
Among diastolic STE parameters, SrIVR was more decreased in T1DM, however, SrE
was more reduced in T2DM. In T1DM, SrS correlated with contractility, SrIVR with
active relaxation, while in T2DM SrE was related to cardiac stiffness,
cardiomyocyte diameter and fibrosis. CONCLUSIONS: Strain and strain rate
parameters can be valuable and feasible measures to describe the dynamic changes
in contractility, active relaxation and LV stiffness in animal models of T1DM and
T2DM. STE corresponds to PV analysis and also correlates with markers of
histological myocardial remodeling.
PMID- 29338776
TI - Takayasu arteritis a cause of hypertensive disorder of pregnancy: a case report.
AB - BACKGROUND: Takayasu arteritis is a rare, chronic, granulomatous systemic
vasculitis of unknown etiology and a few cases have been reported in pregnancy.
In pregnancies concomitant with Takayasu arteritis or after diagnosis, Takayasu
arteritis negatively affects pregnancy by increasing 13-fold the odds of
complications such as hypertensive disorders. The best recommendations in this
scenario are still to be made. CASE PRESENTATION: We present a case of 21-year
old, gravid 1, Mexican woman of Mestizo descent with chronic hypertension
diagnosed since she was 15-years old who presented severe hypertension during
pregnancy (early second trimester); the diagnosis of hypertensive disorder of
pregnancy was ruled out requiring first-line and second-line antihypertensive
therapy without serious associated maternal or fetal morbidity. CONCLUSIONS:
Takayasu arteritis and pregnancy play an important role in maternal and fetal
outcomes. Efforts should be made to further investigate the Takayasu arteritis
diagnosis in pregnant women with refractory hypertension.
PMID- 29338777
TI - Measuring management's perspective of data quality in Pakistan's Tuberculosis
control programme: a test-based approach to identify data quality dimensions.
AB - BACKGROUND: Data quality is core theme of programme's performance assessment and
many organizations do not have any data quality improvement strategy, wherein
data quality dimensions and data quality assessment framework are important
constituents. As there is limited published research about the data quality
specifics that are relevant to the context of Pakistan's Tuberculosis control
programme, this study aims at identifying the applicable data quality dimensions
by using the 'fitness-for-purpose' perspective. RESULTS: Forty-two respondents
pooled a total of 473 years of professional experience, out of which 223 years
(47%) were in TB control related programmes. Based on the responses against 11
practical cases, adopted from the routine recording and reporting system of
Pakistan's TB control programme (real identities of patient were masked),
completeness, accuracy, consistency, vagueness, uniqueness and timeliness are the
applicable data quality dimensions relevant to the programme's context, i.e. work
settings and field of practice. CONCLUSION: Based on a 'fitness-for-purpose'
approach to data quality, this study used a test-based approach to measure
management's perspective and identified data quality dimensions pertinent to the
programme and country specific requirements. Implementation of a data quality
improvement strategy and achieving enhanced data quality would greatly help
organizations in promoting data use for informed decision making.
PMID- 29338778
TI - Increased whole blood FFA2/GPR43 receptor expression is associated with increased
30-day survival in patients with sepsis.
AB - OBJECTIVE: Sepsis is a condition associated with a dysregulated inflammatory
response to infection with significant morbidity. Recent advances have elucidated
the vital role that the short chain fatty acid glycoprotein receptor 43
(FFA2/GPR43) plays in inflammatory and immunomodulatory pathways. We hypothesized
that elevated whole blood GPR43 RNA expression would be associated with increased
30-day survival in patients admitted with sepsis. Patients (n = 93) admitted to
the intensive care unit with the diagnosis of sepsis underwent quantitative real
time PCR within 48 h of intensive care unit admission. Clinical and demographical
parameters were retrospectively extracted from the chart and compared to
quantitative measurements of GPR43 RNA expression. RESULTS: Utilizing logistic
regression, we found that the odds of mortality decreased for every one-unit
increase in GPR43 RNA expression for patients that survived to 30 days [OR =
0.71; 95% CI (0.50, 0.99) p = 0.049]. Using linear regression, we determined that
the increase in whole blood GPR43 expression was not associated with whole blood
white cell count [r = 0.04; 95% CI (-0.16, 0.24); p = 0.70] or body mass index [r
= - 0.07; 95% CI (- 0.23, 0.18); p = 0.81]. We conclude that the GPR43 receptor
plays an integral role in survival during and after sepsis.
PMID- 29338779
TI - Comparing of two different epidemic seasons of bronchiolitis.
AB - Acute bronchiolitis is the most common cause of hospitalizations in infants < 12
months of age and preventive efforts remain the most important strategy to date.
Recently prophylaxis with palivizumab (PLV) was limited to preterm infants with <
29 weeks gestational age (wGA).We performed a single center analysis in preterm
infants (GA between 30 and 32 weeks) and age < 12 months to compare prophylaxis
with PLV and frequency and characteristics of bronchiolitis and bronchiolitis
related hospitalization in two consecutive epidemic seasons (S1 vs S2).We found a
rising trend in rate of bronchiolitis and bronchiolitis-related hospitalization
in S1 vs S2. Among hospitalization, we found an increased morbidity with an
increase in the rate of mechanical ventilation in S2. Additionally,
hospitalization occurred in subjects with younger chronological age in S2
compared with S1.Our result cannot be generalized because deriving from a single
Center and further evaluation on wider simple size are warranted, but it suggests
an increase in the incidence, gravity and precocity of bronchiolitis in 29-32 wGE
preterm infants with the change in National guidelines for prophylaxis.
PMID- 29338780
TI - Coping with dry eyes: a qualitative approach.
AB - BACKGROUND: Dry eye is a common problem that affects many people worldwide,
reducing quality of life and impacting daily activities. A qualitative approach
often used in medicine and other disciplines is used to evaluate how people with
dry eye cope with this impact. METHODS: Six focus group sessions were conducted
at the Singapore National Eye Centre (SNEC), premises of an eye research
institute. These focus groups consist of a spectrum of dry eye sufferers (30
women, 8 men, aged 61 +/- 11.8 years). Standard methods of coding followed by
determination of themes were adhered to. Where classification was difficult,
consensus was made between 3 assessors. RESULTS: Audio-recorded transcripts were
coded in 10 themes by 3 assessors independently. Four of the themes involved
traditional measures such as lid warming, cleansing, lubrication and oral dietary
supplements. The other themes discovered were Traditional Chinese Medicine,
modification of eye-care habits (e.g. wearing sunglasses), environmental
humidity, lifestyle (e.g. sleeping habits), psychological attitude, and lastly
sharing and communication. CONCLUSION: Holistic coping strategies were found to
be prominent in dry eye sufferers from these focus groups, and people tend to
find personalised ways of coping with the impact of dry eye on daily living.
PMID- 29338781
TI - Correlation between disease activity and serum ferritin in clinically amyopathic
dermatomyositis with rapidly-progressive interstitial lung disease: a case
report.
AB - BACKGROUND: Clinically amyopathic dermatomyositis with anti-Melanoma
Differentiation-Associated gene 5 (MDA5) antibody often presents with severe
interstitial lung disease. Although serum ferritin level is known to reflect
interstitial lung disease activity, there are few case reports describing this
association. CASE PRESENTATION: A 58-year-old man was referred to our outpatient
clinic with a 3-week history of cough and respiratory distress. He had erythema
over the V area of the neck and a Gottron's sign. Chest computed tomography
revealed diffuse ground-glass opacities and reticular shadows in both lungs. Test
for anti-MDA5 antibody was positive. After admission, he received triple
combination therapy (methylprednisolone pulse therapy, tacrolimus, and
cyclophosphamide). However, his respiratory condition worsened as the serum
ferritin level increased. Despite no apparent deterioration on chest radiography,
he ultimately died due to respiratory failure. CONCLUSIONS: In this case, triple
combination therapy was not effective for the patient's respiratory condition.
The serum ferritin level was correlated with disease activity and was more useful
than chest radiography for monitoring clinical status.
PMID- 29338782
TI - Evaluation of two health education interventions to improve the varicella
vaccination: a randomized controlled trial from a province in the east China.
AB - BACKGROUND: We evaluated the effect of two Elaboration Likelihood Model (ELM)
based health educational interventions on varicella vaccine (VarV) vaccination
among pregnant women in a province in the east China. METHODS: A prospective
randomized controlled trial was conducted among 200 pregnant women with >=12
gestation weeks to test two interventions, including a messaging video and a
messaging booklet. The participants were randomly assigned into the control
group, the video group or the booklet group. The VarV coverage at 12 and 24
months old was compared among the children of the three groups and relative risks
(RRs) were calculated, by using the coverage of the control group as reference.
The timeliness of VarV was also assessed. Furthermore, differences in the effects
on the knowledge and attitude of VarV vaccination between the two interventions
was evaluated. RESULTS: The VarV coverage of their children by 24 months of age
was 86.4%, 76.1% and 56.7% for the video group, the booklet group and the control
group, respectively. The relative risks (RRs) for the coverage of VarV at 24
months of age were 4.8 (95% CI: 2.06-11.3) for the video group and 2.4 (95% CI:
1.2-5.1) for the booklet group. The means of delays were 57.3 days in the video
group, 76.9 days in the booklet group, and 100.6 days in the control group. The
proportion of women who intended to vaccinate their children with VarV was higher
in the video group than the booklet group (93.9% vs. 82.1%, p < 0.05).
CONCLUSIONS: Our findings indicated that perinatal health education through
booklet or video could improve the coverage and schedule adherence for children's
VarV vaccination.
PMID- 29338783
TI - Children with premature pubarche: is an alterated neonatal 17-Ohp screening test
a predictive factor?
AB - BACKGROUND: Neonatal screening for 21 hydroxylase deficiency is designed to
detect classical form of congenital adrenal hyperplasia (CAH). It is still
unclear whether newborns who result false positives at neonatal screening might
later develop signs of androgen excess. The aim of this study is to verify
whether a slightly elevated 17-OHP at newborn screening is a predictive factor
for premature pubarche. METHODS: We evaluated all infants born between 2001 and
2014 with premature pubarche. In case of increased bone age, they were submitted
to functional tests to find out the cause of their symptoms. Their 17-OHP values
at newborn screening for CAH were reconsidered. RESULTS: We identified 330
patients (269 females, 61 males) with premature pubarche. All these children had
a normal 17-OHP at newborn screening with the exception of a child, born preterm
and not affected by CAH. CONCLUSIONS: An elevated 17-OHP at newborn screening is
not a predictive factor for premature pubarche. A likely cause of increased 17
OHP level at screening is an immaturity of adrenal gland or a neonatal stress.
Therefore a strict follow up of these neonates during childhood is not necessary.
PMID- 29338784
TI - Advancing STI priorities in the SDG era: priorities for action.
AB - The Sustainable Development Goals present an opportunity to reimagine and then
reconfigure the approach to controlling sexually transmitted infections (STIs).
The predilection of STIs for women and for vulnerable populations means that
services that ameliorate STIs, by their nature, enhance equity, a key focus of
the goals. Given the considerable breadth and depth of the goals, it is important
to locate points of convergence between the SDGs and STIs, further craft
synergies with HIV and select a few population groups and settings to prioritise.
There are many opportunities for STI aficionados in this era to advance the field
and global control of these infections.
PMID- 29338785
TI - Benefits of VCE-003.2, a cannabigerol quinone derivative, against inflammation
driven neuronal deterioration in experimental Parkinson's disease: possible
involvement of different binding sites at the PPARgamma receptor.
AB - BACKGROUND: Neuroprotection with cannabinoids in Parkinson's disease (PD) has
been afforded predominantly with antioxidant or anti-inflammatory cannabinoids.
In the present study, we investigated the anti-inflammatory and neuroprotective
properties of VCE-003.2, a quinone derivative of the non-psychotrophic
phytocannabinoid cannabigerol (CBG), which may derive its activity at the
peroxisome proliferator-activated receptor-gamma (PPARgamma). The compound is
also an antioxidant. METHODS: We evaluated VCE-003.2 in an in vivo [mice
subjected to unilateral intrastriatal injections of lipopolysaccharide (LPS)]
model of PD, as well as in in vitro (LPS-exposed BV2 cells and M-213 cells
treated with conditioned media generated from LPS-exposed BV2 cells) cellular
models. The type of interaction of VCE-003.2 at the PPARgamma receptor was
furtherly investigated in bone marrow-derived human mesenchymal stem cells (MSCs)
and sustained with transcriptional assays and in silico docking studies. RESULTS:
VCE-003.2 has no activity at the cannabinoid receptors, a fact that we confirmed
in this study using competition studies. The administration of VCE-003.2 to LPS
lesioned mice attenuated the loss of tyrosine hydroxylase (TH)-containing
nigrostriatal neurons and, in particular, the intense microgliosis provoked by
LPS in the substantia nigra, measured by Iba-1/Cd68 immunostaining. The analysis
by qPCR of proinflammatory mediators such as tumor necrosis factor-alpha (TNF
alpha), interleukin-1beta (IL-1beta), and inducible nitric oxide synthase (iNOS)
in the striatum showed they were markedly elevated by the LPS lesion and strongly
reduced by the treatment with VCE-003.2. The effects of VCE-003.2 in LPS-lesioned
mice implied the activation of PPARgamma receptors, as they were attenuated when
VCE-003.2 was co-administered with the PPARgamma inhibitor T0070907. We then
moved to some in vitro approaches, first to confirm the anti-inflammatory profile
of VCE-003.2 in cultured BV2 cells exposed to LPS. VCE-003.2 was able to
attenuate the synthesis and release of TNF-alpha and IL-1beta, as well as the
induction of iNOS and cyclooxygenase-2 (COX-2) elicited by LPS in these cells.
However, we found such effects were not reversed by GW9662, another classic
PPARgamma antagonist. Next, we investigated the neuroprotective effects of VCE
003.2 in cultured M-213 neuronal cells exposed to conditioned media generated
from LPS-exposed cultured BV2 cells. VCE-003.2 reduced M-213 cell death, but
again, such effects were not reversed by T0070907. Using docking analysis, we
detected that VCE-003.2 binds both the canonical and the alternative binding
sites in the PPARgamma ligand-binding pocket (LBP). Functional assays further
showed that T0070907 almost abolished PPARgamma transcriptional activity induced
by rosiglitazone (RGZ), but it did not affect the activity of VCE-003.2 in a Gal4
Luc system. However, T0070907 inhibited the effects of RGZ and VCE-003.2 on the
expression of PPARgamma-dependent genes upregulated in MSCs. CONCLUSIONS: We have
demonstrated that VCE-003.2 is neuroprotective against inflammation-driven
neuronal damage in an in vivo model of PD and in in vitro cellular models of
neuroinflammation. Such effects might involve PPARgamma receptors, although in
silico and in vitro experiments strongly suggest that VCE-003.2 targets PPARgamma
by acting through two binding sites at the LBP, one that is sensitive to T0070907
(canonical binding site) and other that is not affected by this PPARgamma
antagonist (alternative binding site).
PMID- 29338787
TI - Correction to: Health effects of milder winters: a review of evidence from the
United Kingdom.
AB - CORRECTION: After publication of the article [1], it has been brought to our
attention that there is an error in the abstract. The line that reads "a 1
degrees C fall during winter months led to reductions of 4.5%, 3.9% and 11.2%"
should say "a 1 degrees C fall during winter months led to increases of 4.5%,
3.9% and 11.2%".
PMID- 29338786
TI - A systematic review of transfusion-transmitted malaria in non-endemic areas.
AB - BACKGROUND: Transfusion-transmitted malaria (TTM) is an accidental Plasmodium
infection caused by whole blood or a blood component transfusion from a malaria
infected donor to a recipient. Infected blood transfusions directly release
malaria parasites in the recipient's bloodstream triggering the development of
high risk complications, and potentially leading to a fatal outcome especially in
individuals with no previous exposure to malaria or in immuno-compromised
patients. A systematic review was conducted on TTM case reports in non-endemic
areas to describe the epidemiological characteristics of blood donors and
recipients. METHODS: Relevant articles were retrieved from Pubmed, EMBASE,
Scopus, and LILACS. From each selected study the following data were extracted:
study area, gender and age of blood donor and recipient, blood component
associated with TTM, Plasmodium species, malaria diagnostic method employed,
blood donor screening method, incubation period between the infected transfusion
and the onset of clinical symptoms in the recipient, time elapsed between the
clinical symptoms and the diagnosis of malaria, infection outcome, country of
origin of the blood donor and time of the last potential malaria exposure.
RESULTS: Plasmodium species were detected in 100 TTM case reports with a
different frequency: 45% Plasmodium falciparum, 30% Plasmodium malariae, 16%
Plasmodium vivax, 4% Plasmodium ovale, 2% Plasmodium knowlesi, 1% mixed infection
P. falciparum/P. malariae. The majority of fatal outcomes (11/45) was caused by
P. falciparum whilst the other fatalities occurred in individuals infected by P.
malariae (2/30) and P. ovale (1/4). However, non P. falciparum fatalities were
not attributed directly to malaria. The incubation time for all Plasmodium
species TTM case reports was longer than what expected in natural infections.
This difference was statistically significant for P. malariae (p = 0.006). A
longer incubation time in the recipient together with a chronic infection at low
parasite density of the donor makes P. malariae a subtle but not negligible risk
for blood safety aside from P. falciparum. CONCLUSIONS: TTM risk needs to be
taken into account in order to enhance the safety of the blood supply chain from
donors to recipients by means of appropriate diagnostic tools.
PMID- 29338788
TI - High-throughput immunophenotypic characterization of bone marrow- and cord blood
derived mesenchymal stromal cells reveals common and differentially expressed
markers: identification of angiotensin-converting enzyme (CD143) as a marker
differentially expressed between adult and perinatal tissue sources.
AB - BACKGROUND: Mesenchymal stromal cells (MSC) are a heterogeneous population of
multipotent progenitors used in the clinic because of their immunomodulatory
properties and their ability to differentiate into multiple mesodermal lineages.
Although bone marrow (BM) remains the most common MSC source, cord blood (CB) can
be collected noninvasively and without major ethical concerns. Comparative
studies comprehensively characterizing the MSC phenotype across several tissue
sources are still lacking. This study provides a 246-antigen immunophenotypic
analysis of BM- and CB-derived MSC aimed at identifying common and strongly
expressed MSC markers as well as the existence of discriminating markers between
the two sources. METHODS: BM-MSC (n = 4) were expanded and analyzed as bulk (n =
6) or single clones isolated from the bulk culture (n = 3). CB-MSC (n = 6) were
isolated and expanded as single clones in 5/6 samples. The BM-MSC and CB-MSC
phenotype was investigated by flow cytometry using a panel of 246 monoclonal
antibodies. To define the markers common to both sources, those showing the
smallest variation between samples (coefficient of variation of log2 fold
increase <= 0.5, n = 59) were selected for unsupervised hierarchical cluster
analysis (HCL). Differentially expressed markers were identified by directly
comparing the expression of all 246 antigens between BM-MSC and CB-MSC. RESULTS:
Based on HCL, 18 markers clustered as strongly expressed in BM-MSC and CB-MSC,
including alpha-smooth muscle antigen (SMA), beta-2-microglobulin, CD105, CD13,
CD140b, CD147, CD151, CD276, CD29, CD44, CD47, CD59, CD73, CD81, CD90, CD98, HLA
ABC, and vimentin. All except CD140b and alpha-SMA were suitable for the specific
identification of ex-vivo expanded MSC. Notably, only angiotensin-converting
enzyme (CD143) was exclusively expressed on BM-MSC. CD143 expression was tested
on 10 additional BM-MSC and CB-MSC and on 10 umbilical cord- and adipose tissue
derived MSC samples, confirming that its expression is restricted to adult
sources. CONCLUSIONS: This is the first study that has comprehensively compared
the phenotype of BM-MSC and CB-MSC. We have identified markers that could
complement the minimal panel proposed for the in-vitro MSC definition, being
shared and strongly expressed by BM- and CB-derived MSC. We have also identified
CD143 as a marker exclusively expressed on MSC derived from adult tissue sources.
Further studies will elucidate the biological role of CD143 and its potential
association with tissue-specific MSC features.
PMID- 29338790
TI - Morphometric characterisation of human tracheas: focus on cartilaginous ring
variation.
AB - PURPOSE: Details regarding tracheal anatomy are currently lacking, with existing
literature focussing mainly on the cricoid-tracheal region or the carina.
External gross anatomy and internal morphology throughout the entire trachea is
important for normal physiological functioning and various clinical applications
such as designs for tracheal implants or endotracheal devices. OBJECTIVE: To
determine quantitative and qualitative characteristics of gross tracheal and
individual tracheal ring anatomy. METHOD: 10 tracheas were harvested from
formaldehyde-fixed cadavers. Tracheal length, height and inter-ring distance were
measured from complete tracheas. Individual rings were excised and the following
measurements were taken at three points on the ring: thickness, width, and antero
posterior (A-P) length. RESULTS: The average tracheal length was 10.38 +/- 0.85
cm with a mean of 19 +/- 3 rings per trachea. The average width and A-P diameter
of tracheal lumens were 17.31 +/- 2.57 and 17.27 +/- 2.56 mm, with a width-AP
ratio of 1.00 ('C' shaped ring). The A-P diameter shows a trend of narrowing
slightly from the upper 1/3 to the lower 1/3 of the trachea. While majority of
tracheal rings consisted of the expected 'C' shape, more than 41% of the 147
counted rings consisted of abnormally shaped rings which were further analysed.
CONCLUSION: This study provides further details regarding tracheal anatomy which
will be useful for implant design. Of interest for anatomists, is the marked
variability in tracheal ring morphology which could be further characterised in
larger studies.
PMID- 29338791
TI - Associations of the hypertension-related single nucleotide polymorphism
rs11191548 with high-density lipoprotein cholesterol and leptin in Chinese
children.
AB - BACKGROUND: The genome-wide association study has founded hypertension-related
single nucleotide polymorphism (SNP) rs11191548 near CYP17A1 encoding a key
enzyme involved in steroid metabolism, but the molecular mechanisms are not
understood and the associations of the SNP with hypertension-related traits are
not fully described, especially in children. The aim of the present study is to
investigate the associations between the SNP and two hypertension-related traits,
lipids and leptin. METHODS: We genotyped the SNP in Beijing Child and Adolescent
Metabolic Syndrome (BCAMS) study. A total of 3503 children participated in the
study. RESULTS: The SNP rs11191548 was significantly associated with high-density
lipoprotein cholesterol (HDL) (P = 0.014 and 0.028, respectively) and leptin (P =
0.011 and 0.026, respectively) under an additive model after adjustment for age,
gender, and systolic blood pressure (SBP) or diastolic blood pressure (DBP).
There was a statistically significant association of rs11191548 with high leptin
after adjustment for age, gender, and SBP or DBP. The P-values remain significant
after correction for multiple testing. CONCLUSIONS: We demonstrate for the first
time that the SNP rs11191548 near CYP17A1 is associated with HDL and leptin in
Chinese children. These novel findings provide important evidence that HDL and
leptin maybe possibly mediate the process of CYP17A1 involved in hypertension.
PMID- 29338789
TI - Diagnosis, treatment, and response assessment in solitary plasmacytoma: updated
recommendations from a European Expert Panel.
AB - Solitary plasmacytoma is an infrequent form of plasma cell dyscrasia that
presents as a single mass of monoclonal plasma cells, located either
extramedullary or intraosseous. In some patients, a bone marrow aspiration can
detect a low monoclonal plasma cell infiltration which indicates a high risk of
early progression to an overt myeloma disease. Before treatment initiation, whole
body positron emission tomography-computed tomography or magnetic resonance
imaging should be performed to exclude the presence of additional malignant
lesions. For decades, treatment has been based on high-dose radiation, but
studies exploring the potential benefit of systemic therapies for high-risk
patients are urgently needed. In this review, a panel of expert European
hematologists updates the recommendations on the diagnosis and management of
patients with solitary plasmacytoma.
PMID- 29338793
TI - The institutional context of tobacco production in Zambia.
AB - BACKGROUND: Tobacco production is said to be an important contributor to Zambia's
economy in terms of labour and revenue generation. In light of Zambia's
obligations under the WHO Framework Convention of Tobacco Control (FCTC) we
examined the institutional actors in Zambia's tobacco sector to better understand
their roles and determine the institutional context that supports tobacco
production in Zambia. METHODS: Findings from 26 qualitative, semi-structured
individual or small-group interviews with key informants from governmental,
intergovernmental and non-governmental organisations were analysed, along with
data and information from published literature. RESULTS: Although Zambia is
obligated under the FCTC to take steps to reduce tobacco production, the
country's weak economy and strong tobacco interests make it difficult to achieve
this goal. Respondents uniformly acknowledged that growing the country's economy
and ensuring employment for its citizens are the government's top priorities.
Lacklustre coordination and collaboration between the institutional actors, both
within and outside government, contributes to an environment that helps sustain
tobacco production in the country. A Tobacco Products Control Bill has been under
review for a number of years, but with no supply measures included, and with no
indication of when or whether it will be passed. CONCLUSIONS: As with other low
income countries involved in tobacco production, there is inconsistency between
Zambia's economic policy to strengthen the country's economy and its FCTC
commitment to regulate and control tobacco production. The absence of a whole-of
government approach towards tobacco control has created an institutional context
of duelling objectives, with some government ministries working at cross-purposes
and tobacco interests left unchecked. With no ultimate coordinating authority,
this industry risks being run according to the desire and demands of
multinational tobacco companies, with few, if any, checks against them.
PMID- 29338794
TI - A SYSTEMATIC REVIEW OF GROUP WALKING IN PHYSICALLY HEALTHY PEOPLE TO PROMOTE
PHYSICAL ACTIVITY.
AB - BACKGROUND: Walking is a good way to meet physical activity guidelines. We
examined the effectiveness of walking in groups compared with walking alone or
inactive controls in physically healthy adults on physical activity and quality
of life. (PROSPERO CRD42016033752). METHODS: We searched Medline, Embase, Cinahl,
Web of Knowledge Science Citation Index, and Cochrane CENTRAL until March 2016,
for any comparative studies, in physically healthy adults, of walking in groups
compared with inactive controls or walking alone, reporting any measure of
physical activity. We searched references from recent relevant systematic
reviews. Two reviewers checked study eligibility and independently extracted
data. Disagreements were resolved through discussion. Quality was assessed using
likelihood of selection, performance, attrition, and detection biases. Meta
analysis was conducted using Review Manager 5.3. RESULTS: From 1,404 citations,
18 studies were included in qualitative synthesis and 10 in meta-analyses.
Fourteen compared group walking to inactive controls and four to walking alone.
Eight reported more than one measure of physical activity, none reported
according to current guidelines. Group walking compared with inactive controls
increased follow-up physical activity (9 randomized controlled trials,
standardized mean difference [SMD] 0.58 [95 percent confidence interval {CI},
0.34-0.82] to SMD 0.43 [95 percent CI, 0.20-0.66]). Compared with walking alone,
studies were too few and too heterogeneous to conduct meta-analysis, but the
trend was improved physical activity at follow-up for group walking participants.
Seven (all inactive control) reported quality-of-life: five showed statistically
significantly improved scores. DISCUSSION: Better evidence may encourage
government policy to promote walking in groups. Standardized physical activity
outcomes need to be reported in research.
PMID- 29338792
TI - Critical inhaler errors in asthma and COPD: a systematic review of impact on
health outcomes.
AB - BACKGROUND: Inhaled drug delivery is the cornerstone treatment for asthma and
chronic obstructive pulmonary disease (COPD). However, use of inhaler devices can
be challenging, potentially leading to critical errors in handling that can
significantly reduce drug delivery to the lungs and effectiveness of treatment.
METHODS: A systematic review was conducted to define 'critical' errors and their
impact on health outcomes and resource use between 2004 and 2016, using key
search terms for inhaler errors in asthma and COPD (Search-1) and associated
health-economic and patient burden (Search-2). RESULTS: Search-1 identified 62
manuscripts, 47 abstracts, and 5 conference proceedings (n = 114 total). Search-2
identified 9 studies. We observed 299 descriptions of critical error. Age,
education status, previous inhaler instruction, comorbidities and socioeconomic
status were associated with worse handling error frequency. A significant
association was found between inhaler errors and poor disease outcomes
(exacerbations), and greater health-economic burden. CONCLUSIONS: We have shown
wide variations in how critical errors are defined, and the evidence shows an
important association between inhaler errors and worsened health outcomes. Given
the negative impact diminished disease outcomes impose on resource use, our
findings highlight the importance of achieving optimal inhaler technique, and a
need for a consensus on defining critical and non-critical errors.
PMID- 29338795
TI - The first report of Xenorhabdus indica from Steinernema pakistanense: co
phylogenetic study suggests co-speciation between X. indica and its
steinernematid nematodes.
AB - During a survey in agricultural fields of the sub-humid region of Meerut
district, India, two strains of entomopathogenic nematodes, labelled CS31 and
CS32, were isolated using the Galleria baiting technique. Based on morphological
and morphometric studies, and molecular data, the nematodes were identified as
Steinernema pakistanense, making this finding the first report of this species
from India. For the first time, we performed a molecular and biochemical
characterization of the bacterial symbiont of S. pakistanense. Furthermore, a co
phylogenetic analysis of the bacteria from the monophyletic clade containing a
symbiont of S. pakistanense, together with their nematode hosts, was conducted,
to test the degree of nematode-bacteria co-speciation. Both isolates were also
tested in a laboratory assay for pathogenicity against two major pests,
Helicoverpa armigera and Spodoptera litura. The morphology of the Indian isolates
corresponds mainly to the original description, with the only difference being
the absence of a mucron in first-generation females and missing epiptygmata in
the second generation. The sequences of bacterial recA and gyrB genes have shown
that the symbiont of S. pakistanense is closely related to Xenorhabdus indica,
which is associated with some other nematodes from the 'bicornutum' group. Co
phylogenetic analysis has shown a remarkable congruence between the nematode and
bacterial phylogenies, suggesting that, in some lineages within the Steinernema /
Xenorhabdus complex, the nematodes and bacteria have undergone co-speciation. In
the virulence assay, both strains caused a 100% mortality of both tested insects
after 48 h, even at the lowest doses of 25 infective juveniles per insect,
suggesting that S. pakistanense could be considered for use in the biocontrol of
these organisms in India.
PMID- 29338796
TI - Cortical morphology development in patients with 22q11.2 deletion syndrome at
ultra-high risk of psychosis.
AB - BACKGROUND: Patients with 22q11.2 deletion syndrome (22q11DS) present a high risk
of developing psychosis. While clinical and cognitive predictors for the
conversion towards a full-blown psychotic disorder are well defined and largely
used in practice, neural biomarkers do not yet exist. However, a number of
investigations indicated an association between abnormalities in cortical
morphology and higher symptoms severities in patients with 22q11DS. Nevertheless,
few studies included homogeneous groups of patients differing in their psychotic
symptoms profile. METHODS: In this study, we included 22 patients meeting the
criteria for an ultra-high-risk (UHR) psychotic state and 22 age-, gender- and IQ
matched non-UHR patients. Measures of cortical morphology, including cortical
thickness, volume, surface area and gyrification, were compared between the two
groups using mass-univariate and multivariate comparisons. Furthermore, the
development of these measures was tested in the two groups using a mixed-model
approach. RESULTS: Our results showed differences in cortical volume and surface
area in UHR patients compared with non-UHR. In particular, we found a positive
association between surface area and the rate of change of global functioning,
suggesting that higher surface area is predictive of improved functioning with
age. We also observed accelerated cortical thinning during adolescence in UHR
patients with 22q11DS. CONCLUSIONS: These results, although preliminary, suggest
that alterations in cortical volume and surface area as well as altered
development of cortical thickness may be associated to a greater probability to
develop psychosis in 22q11DS.
PMID- 29338797
TI - Maternal early pregnancy obesity and depressive symptoms during and after
pregnancy.
AB - BACKGROUND: Previous studies have linked maternal obesity with depressive
symptoms during and after pregnancy. It remains unknown whether obesity
associates with consistently elevated depressive symptoms throughout pregnancy,
predicts symptoms postpartum when accounting for antenatal symptoms, and if co
morbid hypertensive and diabetic disorders add to these associations. We
addressed these questions in a sample of Finnish women whom we followed during
and after pregnancy. METHODS: Early pregnancy body mass index, derived from the
Finnish Medical Birth Register and hospital records in 3234 PREDO study
participants, was categorized into underweight (<18.5 kg/m2), normal weight (18.5
24.99 kg/m2), overweight (25-29.99 kg/m2), and obese (?30 kg/m2) groups. The
women completed the Center for Epidemiological Studies Depression Scale biweekly
during pregnancy, and at 2.4 (s.d. = 1.2) and/or 28.2 (s.d. = 4.2) weeks after
pregnancy. RESULTS: In comparison to normal weight women, overweight, and obese
women reported higher levels of depressive symptoms and had higher odds of
clinically significant depressive symptoms during (23% and 43%, respectively) and
after pregnancy (22% and 36%, respectively). Underweight women had 68% higher
odds of clinically significant depressive symptoms after pregnancy. Overweight
and obesity also predicted higher depressive symptoms after pregnancy in women
not reporting clinically relevant symptomatology during pregnancy. Hypertensive
and diabetic disorders did not explain or add to these associations. CONCLUSIONS:
Maternal early pregnancy overweight and obesity and depressive symptoms during
and after pregnancy are associated. Mental health promotion should be included as
an integral part of lifestyle interventions in early pregnancy obesity and
extended to benefit also overweight and underweight women.
PMID- 29338798
TI - High diversity and low genetic structure of feather mites associated with a
phenotypically variable bird host.
AB - Obligate symbionts may be genetically structured among host individuals and among
phenotypically distinct host populations. Such processes may in turn determine
within-host genetic diversity of symbionts, which is relevant for understanding
symbiont population dynamics. We analysed the population genetic structure of two
species of feather mites (Proctophyllodes sylviae and Trouessartia bifurcata) in
migratory and resident blackcaps Sylvia atricapilla that winter sympatrically.
Resident and migratory hosts may provide mites with habitats of different
qualities, what might promote specialization of mite populations. We found high
genetic diversity of within-host populations for both mite species, but no sign
of genetic structure of mites between migratory and resident hosts. Our results
suggest that, although dispersal mechanisms between hosts during the non-breeding
season are unclear, mite populations are not limited by transmission bottlenecks
that would reduce genetic diversity among individuals that share a host.
Additionally, there is no evidence that host phenotypic divergence (associated
with the evolution of migration and residency) has promoted the evolution of host
specialist mite populations. Unrestricted dispersal among host types may allow
symbiotic organisms to avoid inbreeding and to persist in the face of habitat
heterogeneity in phenotypically diverse host populations.
PMID- 29338799
TI - Going it Alone: A Scoping Review of Unbefriended Older Adults.
AB - Older adults who have reduced decision-making capacity and no family or friends
to compensate for these deficiencies are known as unbefriended and require a
public guardian. The purpose of this study was to review the peer-reviewed and
grey literature to determine the scope of available research on unbefriended
older adults in Canada and the United States. We found limited research examining
unbefriended older adults. No Canadian studies or reports were located.
Unbefriended older adults were childless or had fewer children, were more
cognitively impaired, and were older than older adults who were not unbefriended.
These findings demonstrate a stark scarcity of studies on unbefriended older
adults. Research is urgently needed using standardized data collection of
guardianship status in order to enable studies of the prevalence of public
guardianship in Canada.
PMID- 29338800
TI - A Preliminary Investigation of Pathways to Inflated Responsibility Beliefs in
Children with Obsessive Compulsive Disorder.
AB - BACKGROUND: Cognitive theorists posit that inflated responsibility beliefs
contribute to the development of obsessive compulsive disorder (OCD). Salkovskis
et al. (1999) proposed that experiencing heightened responsibility,
overprotective parents and rigid rules, and thinking one influenced or caused a
negative life event act as 'pathways' to the development of inflated
responsibility beliefs, thereby increasing risk for OCD. Studies in adults with
OCD and non-clinical adolescents support the link between these experiences and
responsibility beliefs (Coles et al., 2015; Halvaiepour and Nosratabadi, 2015),
but the theory has never been tested in youth with current OCD. AIMS: We provided
an initial test of the theory by Salkovskis et al. (1999) in youth with OCD. We
predicted that childhood experiences proposed by Salkovskis et al. (1999) would
correlate positively with responsibility and harm beliefs and OCD symptom
severity. METHOD: Twenty youth with OCD (age 9-16 years) completed a new child
report measure of the experiences hypothesized by Salkovskis et al. (1999), the
Pathways to Inflated Responsibility Beliefs Scale-Child Version (PIRBS-CV). Youth
also completed the Obsessive Beliefs Questionnaire-Child Version (Coles et al.,
2010) and the Obsessive Compulsive Inventory-Child Version (Foa et al., 2010).
RESULTS: Consistent with hypotheses, the PIRBS-CV was significantly related to
responsibility and harm beliefs and OCD symptom severity. CONCLUSIONS: Results
provide initial support for the theory proposed by Salkovskis et al. (1999) as
applied to youth with OCD. Future studies are needed to further assess the model
in early-onset OCD.
PMID- 29338801
TI - How immediate and significant is the outcome of training on diversified diets,
hygiene and food safety? An effort to mitigate child undernutrition in rural
Malawi.
AB - OBJECTIVE: The present study examined the impacts of training on nutrition,
hygiene and food safety designed by the Nutrition Working Group, Child Survival
Collaborations and Resources Group (CORE). DESIGN: Adapted from the 21d Positive
Deviance/Hearth model, mothers were trained on the subjects of appropriate
complementary feeding, water, sanitation and hygiene (WASH) practices, and
aflatoxin contamination in food. To assess the impacts on child undernutrition, a
randomised controlled trial was implemented on a sample of 179 mothers and their
children (<2 years old) in two districts of Malawi, namely Mzimba and Balaka.
Settings A 21d intensive learning-by-doing process using the positive deviance
approach. SUBJECTS: Malawian children and mothers. RESULTS: Difference-in
difference panel regression analysis revealed that the impacts of the
comprehensive training were positive and statistically significant on the Z
scores for wasting and underweight, where the effects increased constantly over
time within the 21d time frame. As for stunting, the coefficients were not
statistically significant during the 21d programme, although the level of
significance started increasing in 2 weeks, indicating that stunting should also
be alleviated in a slightly longer time horizon. CONCLUSIONS: The study clearly
suggests that comprehensive training immediately guides mothers into improved
dietary and hygiene practices, and that improved practices take immediate and
progressive effects in ameliorating children's undernutrition.
PMID- 29338802
TI - Separating Common from Unique Variance Within Emotional Distress: An Examination
of Reliability and Relations to Worry.
AB - BACKGROUND: High comorbidity rates among emotional disorders have led researchers
to examine transdiagnostic factors that may contribute to shared psychopathology.
Bifactor models provide a unique method for examining transdiagnostic variables
by modelling the common and unique factors within measures. Previous findings
suggest that the bifactor model of the Depression Anxiety and Stress Scale (DASS)
may provide a method for examining transdiagnostic factors within emotional
disorders. AIMS: This study aimed to replicate the bifactor model of the DASS, a
multidimensional measure of psychological distress, within a US adult sample and
provide initial estimates of the reliability of the general and domain-specific
factors. Furthermore, this study hypothesized that Worry, a theorized
transdiagnostic variable, would show stronger relations to general emotional
distress than domain-specific subscales. METHOD: Confirmatory factor analysis was
used to evaluate the bifactor model structure of the DASS in 456 US adult
participants (279 females and 177 males, mean age 35.9 years) recruited online.
RESULTS: The DASS bifactor model fitted well (CFI = 0.98; RMSEA = 0.05). The
General Emotional Distress factor accounted for most of the reliable variance in
item scores. Domain-specific subscales accounted for modest portions of reliable
variance in items after accounting for the general scale. Finally, structural
equation modelling indicated that Worry was strongly predicted by the General
Emotional Distress factor. CONCLUSIONS: The DASS bifactor model is generalizable
to a US community sample and General Emotional Distress, but not domain-specific
factors, strongly predict the transdiagnostic variable Worry.
PMID- 29338803
TI - Socio-demographic inequalities in the clinical characteristics of dengue
haemorrhagic fever in the city of Rio de Janeiro, Brazil, 2007-2008.
AB - In 2007-2008, the city of Rio de Janeiro underwent an epidemiological change,
with increases in the incidence in children and in severe forms of dengue. To
describe the clinical profile and spatial distribution of dengue we performed an
ecological study based on dengue surveillance data using the Brazilian
classification (2005): dengue fever, dengue haemorrhagic fever (DHF) and dengue
with complications. chi 2 test was used to describe the clinical and socio
demographic variables (P < 0.05). Spatial distribution of incidence and case
fatality was explored with thematic maps, Moran and Geary indices (P < 0.05). Of
the total of 151 527 dengue cases, 38 808 met the inclusion criteria; 42.4% <18
years; 22.9% dengue with complications and 2.7% DHF. Case-fatality was higher in
infants (1.4%) and in DHF (7.7%). Bleeding was more frequent in adolescents and
adults while plasma leakage was more common in preschoolers and schoolchildren.
The highest incidence was found in the West Zone of the city, in a different area
from that of the worst case-fatality (P < 0.05). Although the incidence of DHF
was higher in schoolchildren, infants showed higher case-fatality. The area with
the highest case-fatality did not present the highest incidence, which suggests
problems in the organization of health services.
PMID- 29338804
TI - Public health response to a measles outbreak on a university campus in Australia,
2015.
AB - This report describes the effective public health response to a measles outbreak
involving a university campus in Brisbane, Australia. Eleven cases in total were
notified, mostly university students. The public health response included
targeted measles vaccination clinics which were established on campus and focused
on student groups most likely to have been exposed. The size of the university
population, social interaction between students on and off campus, as well as
limited vaccination records for the university community presented challenges for
the control of this extremely infectious illness. We recommend domestic students
ensure vaccinations are current prior to matriculation. Immunisation information
should be included in university student enrolment packs. Incoming international
students should ensure routine vaccinations are up-to-date prior to arrival in
Australia, thereby reducing the risk of importation of measles and other
infectious diseases.
PMID- 29338805
TI - Risk factors for infectiousness of patients with tuberculosis: a systematic
review and meta-analysis.
AB - We performed a systematic review and meta-analyses of studies assessing
tuberculosis (TB) patient-related risk factors for transmission of Mycobacterium
tuberculosis infection. Meta-analyses were conducted for sputum smear-positivity,
lung cavitation and HIV seropositivity of index patients with both crude and
adjusted odds ratios (AORs) pooled using random effect models. Thirty-seven
studies were included in the review. We found that demographic characteristics
such as age and sex were not significant risk factors, while behaviours such as
smoking and alcohol intake were associated with infectiousness although
inconsistently. Treatment delay of >28 days was a significant predictor of
greater infectiousness. Contacts of sputum smear-positive index patients were
found to be more likely to be infected than contacts of sputum smear-negative
patients, with a pooled AOR of 2.15 (95% confidence interval (CI) 1.47-3.17, I 2
= 38%). Similarly, contacts of patients with the cavitary disease were around
twice as likely to be infected as contacts of patients without cavitation (pooled
AOR 1.9, 95% CI 1.26-2.84, I 2 = 63%). In contrast, HIV seropositive patients
were associated with few contact infections than HIV seronegative patients (AOR
0.45, 95% CI 0.26-0.80, I 2 = 52%). In conclusion, behavioural and clinical
characteristics of TB patients can be used to identify highly infectious patients
for targeted interventions.
PMID- 29338806
TI - Cancer pain management needs and perspectives of patients from Chinese
backgrounds: a systematic review of the Chinese and English literature.
AB - OBJECTIVE: More than half of all cancer patients experience unrelieved pain.
Culture can significantly affect patients' cancer pain-related beliefs and
behaviors. Little is known about cultural impact on Chinese cancer patients' pain
management. The objective of this review was to describe pain management
experiences of cancer patients from Chinese backgrounds and to identify barriers
affecting their pain management. METHOD: A systematic review was conducted
adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses
guidelines. Studies were included if they reported pain management experiences of
adult cancer patients from Chinese backgrounds. Five databases were searched for
peer-reviewed articles published in English or Chinese journals between1990 and
2015. The quality of included studies was assessed using Joanna Briggs
Institution's appraisal tools. RESULTS: Of 3,904 identified records, 23 articles
met criteria and provided primary data from 6,110 patients. Suboptimal analgesic
use, delays in receiving treatment, reluctance to report pain, and/or poor
adherence to prescribed analgesics contributed to the patients' inadequate pain
control. Patient-related barriers included fatalism, desire to be good, low pain
control belief, pain endurance beliefs, and negative effect beliefs. Patients and
family shared barriers about fear of addiction and concerns on analgesic side
effects and disease progression. Health professional-related barriers were poor
communication, ineffective management of pain, and analgesic side effects.
Healthcare system-related barriers included limited access to analgesics and/or
after hour pain services and lack of health insurance. Significance of results
Chinese cancer patients' misconceptions regarding pain and analgesics may present
as the main barriers to optimal pain relief. Findings of this review may inform
health interventions to improve cancer pain management outcomes for patients from
Chinese backgrounds. Future studies on patients' nonpharmacology intervention
related experiences are required to inform multidisciplinary and biopsychosocial
approaches for culturally appropriate pain management.
PMID- 29338807
TI - Genetic diversity of Blastocystis in non-primate animals.
AB - Blastocystis is an anaerobic protist, commonly inhabiting the intestinal tract of
both humans and other animals. Blastocystis is extremely diverse comprising 17
genetically distinct subtypes in mammals and birds. Pathogenicity of this enteric
microbe is currently disputed and knowledge regarding its distribution, diversity
and zoonotic potential is fragmentary. Most research has focused on Blastocystis
from primates, while sampling from other animals remains limited. Herein, we
investigated the prevalence and distribution of Blastocystis in animals held
within a conservation park in South East England. A total of 118 samples were
collected from 27 vertebrate species. The barcoding region of the small-subunit
ribosomal RNA was used for molecular identification and subtyping. Forty one per
cent of the species were sequence positive for Blastocystis indicating a high
prevalence and wide distribution among the animals in the park. Six subtypes were
identified, one of which is potentially novel. Moreover, the majority of animals
were asymptomatic carriers, suggesting that Blastocystis is not pathogenic in
animals. This study provides a thorough investigation of Blastocystis prevalence
within a wildlife park in the UK and can be used as a platform for further
investigations on the distribution of other eukaryotic gut microbes.
PMID- 29338808
TI - Ceratomyxa gracillima n. sp. (Cnidaria: Myxosporea) provides evidence of panmixia
and ceratomyxid radiation in the Amazon basin.
AB - We describe a new freshwater myxosporean species Ceratomyxa gracillima n. sp.
from the gall bladder of the Amazonian catfish Brachyplatystoma rousseauxii; the
first myxozoan recorded in this host. The new Ceratomyxa was described on the
basis of its host, myxospore morphometry, ssrDNA and internal transcribed spacer
region (ITS-1) sequences. Infected fish were sampled from geographically distant
localities: the Tapajos River, Para State, the Amazon River, Amapa State and the
Solimoes River, Amazonas State. Immature and mature plasmodia were slender,
tapered at both ends, and exhibited vermiform motility. The ribosomal sequences
from parasite isolates from the three localities were identical, and distinct
from all other Ceratomyxa sequences. No population-level genetic variation was
observed, even in the typically more variable ITS-1 region. This absence of
genetic variation in widely separated parasite samples suggests high gene flow as
a result of panmixia in the parasite populations. Maximum likelihood and maximum
parsimony analyses placed C. gracillima n. sp. sister to Ceratomyxa vermiformis
in a subclade together with Ceratomyxa brasiliensis and Ceratomyxa amazonensis,
all of which have Amazonian hosts. This subclade, together with other Ceratomyxa
from freshwater hosts, formed an apparently early diverging lineage. The
Amazonian freshwater Ceratomyxa species may represent a radiation that originated
during marine incursions into the Amazon basin that introduced an ancestral
lineage in the late Oligocene or early Miocene.
PMID- 29338810
TI - Detection of mcr-4 positive Salmonella enterica serovar Typhimurium in clinical
isolates of human origin, Italy, October to November 2016.
AB - In this study we report the detection of the recently described mcr-4 gene in two
human isolates of Salmonella enterica serovar Typhimurium. The strains were
isolated from faecal samples of two Italian patients with gastroenteritis,
collected in 2016. The identified mcr-4 genes (variant mcr-4.2) differed from the
mcr-4 gene originally described in a Salmonella strain of swine origin from
Italy. Salmonella species could represent a hidden reservoir for mcr genes.
PMID- 29338811
TI - Ongoing nationwide outbreak of Salmonella Agona associated with internationally
distributed infant milk products, France, December 2017.
AB - On 1 December 2017, an outbreak of Salmonella Agona infections among infants was
identified in France. To date, 37 cases (median age: 4 months) and two further
international cases have been confirmed. Five different infant milk products
manufactured at one facility were implicated. On 2 and 10 December, the company
recalled the implicated products; on 22 December, all products processed at the
facility since February 2017. Trace-forward investigations indicated product
distribution to 66 countries.
PMID- 29338809
TI - Comparison of influenza vaccine effectiveness in preventing outpatient and
inpatient influenza cases in older adults, northern Spain, 2010/11 to 2015/16.
AB - IntroductionWe compared trivalent inactivated influenza vaccine effectiveness
(VE) in preventing outpatient and inpatient influenza cases in Navarre, Spain.
Methods: During seasons 2010/11 to 2015/16, community-dwelling patients with
influenza-like illness aged 50 years or older were tested for influenza when
attended by sentinel general practitioners or admitted to hospitals. The test
negative design was used to estimate and compare the VE by healthcare setting.
Results: We compared 1,242 laboratory-confirmed influenza cases (557 outpatient
and 685 inpatient cases) and 1,641 test-negative controls. Influenza VE was 34%
(95% confidence interval (CI): 6 to 54) in outpatients and 32% (95% CI: 15 to 45)
in inpatients. VE in outpatients and inpatients was, respectively, 41% (95% CI:
1 to 65) and 36% (95% CI: 12 to 53) against A(H1N1)pdm09, 5% (95% CI: -58 to 43)
and 22% (95% CI: -9 to 44) against A(H3N2), and 49% (95% CI, 6 to 73) and 37%
(95% CI: 2 to 59) against influenza B. Trivalent inactivated influenza vaccine
was not associated with a different probability of hospitalisation among
influenza cases, apart from a 54% (95% CI: 10 to 76) reduction in hospitalisation
of influenza A(H3N2) cases. Conclusions: On average, influenza VE was moderate
and similar in preventing outpatient and inpatient influenza cases over six
influenza seasons in patients above 50 years of age. In some instances of low VE,
vaccination may still reduce the risk of hospitalisation in older adults with
vaccine failure.
PMID- 29338812
TI - Comprehensive assessment of the quality of Salmonella whole genome sequence data
available in public sequence databases using the Salmonella in silico Typing
Resource (SISTR).
AB - Public health and food safety institutions around the world are adopting whole
genome sequencing (WGS) to replace conventional methods for characterizing
Salmonella for use in surveillance and outbreak response. Falling costs and
increased throughput of WGS have resulted in an explosion of data, but questions
remain as to the reliability and robustness of the data. Due to the critical
importance of serovar information to public health, it is essential to have
reliable serovar assignments available for all of the Salmonella records. The
current study used a systematic assessment and curation of all Salmonella in the
sequence read archive (SRA) to assess the state of the data and their utility. A
total of 67 758 genomes were assembled de novo and quality-assessed for their
assembly metrics as well as species and serovar assignments. A total of 42 400
genomes passed all of the quality criteria but 30.16 % of genomes were deposited
without serotype information. These data were used to compare the concordance of
reported and predicted serovars for two in silico prediction tools, multi-locus
sequence typing (MLST) and the Salmonella in silico Typing Resource (SISTR),
which produced predictions that were fully concordant with 87.51 and 91.91 % of
the tested isolates, respectively. Concordance of in silico predictions increased
when serovar variants were grouped together, 89.25 % for MLST and 94.98 % for
SISTR. This study represents the first large-scale validation of serovar
information in public genomes and provides a large validated set of genomes,
which can be used to benchmark new bioinformatics tools.
PMID- 29338813
TI - Note from the editors: As time goes by.
PMID- 29338814
TI - The Use of Visual Examination for Determining the Presence of Gluten-Containing
Grains in Gluten Free Oats and Other Grains, Seeds, Beans, Pulses, and Legumes.
AB - Obtaining representative test samples for antibody-based testing is challenging
when analyzing whole grains for gluten. When whole grains are ground into flour
for testing, confocal microscopy studies have shown that gluten tends to exist as
aggregates within the starch background, making single-sample testing inaccurate
and complicating the ability to arrive at an accurate average from multiple
samples. In addition, whole-grain products present a unique risk to gluten free
consumers, in that any contamination is localized to specific servings rather
than being distributed across the product lot. This makes parts-per-million
values less relevant for whole-grain products. Intact grains, seeds, beans,
pulses, and legumes offer an alternative opportunity for gluten detection, in
that contaminating gluten-containing grains (GCGs) are visible and identifiable
to the trained eye or properly calibrated optical sorting equipment. The purpose
of the current study was to determine a Gluten Free Certification Organization
threshold level for the maximum number of GCGs within a kilogram of nongluten
grains sold as specially processed gluten free product and to determine the
feasibility of this threshold by evaluating visual examination data from two
major oat processors.
PMID- 29338815
TI - Correlation between the Expression of High Temperature Requirement Serine
Protease A1 in Nucleus Pulposus Tissue and the Degree of Intervertebral Disc
Degeneration.
AB - Objective To investigate the correlation between the expression level of high
temperature requirement serine protease A1 (HtrA1) in nucleus pulposus and the
degree of intervertebral disc degeneration (Pfirrmann grade).Methods Thirty-six
patients who underwent excision of nucleus pulposus were examined by magnetic
resonance imaging (MRI) before operation,and the Pfirrmann grading of all
patients was performed according to the sagittal T2 weighted MRI.The expression
of HtrA1 in nucleus pulposus tissue was detected by reverse transcription
polymerase chain reaction and Western blot.The correlation between the expression
level of HtrA1 in nucleus pulposus tissue and Pfirrmann grade was
analyzed.Results MRI in all 36 patients showed that there were 3 cases of
Pfirrmann grade I,10 cases of grade II,11 cases of grade III,7 cases of grade
III,and 5 cases of grade V.The mRNA and protein expressions of HtrA1 in nucleus
pulposus tissue increased with the increase of Pfirrmann grade.There were
significant differences in the expression level of HtrA1 among different
Pfirrmann grade groups (P<0.05) except for the difference between grade III and V
(P>0.05).Spearman rank correlation analysis revealed that there was a rank
correlation between expression level of HtrA1 and Pfirrmann grade (P<0.000
1).Conclusion The mRNA and protein expressions of HtrA1 in nucleus pulposus
tissue increase with the increase of Pfirrmann grade,indicating HtrA1 is
correlated with the degree of intervertebral disc degeneration.
PMID- 29338816
TI - Fabrication of Isoniazid/Rifampicin/Poly L-lactic Acid Donut-shaped Implants via
Three Dimensional Printing Technique.
AB - Objective To investigate the possibility of manufacturing dual-drug loaded
isoniazid/rifampicin/poly L-lactic acid (PLLA) implant with donut-shaped
structure via three-dimensional (3D) printing technique and study the drug
release characteristic and biocompatibility of the implant in vitro.Methods PLLA
was crushed into particles with diameters around 75-100 MUm.Isoniazid and
rifampicin bulk drugs were dissolved into the organic dissolvent respectively to
be the binding liquid.The 3D printing machine fabricated the donut-shaped implant
via binding the PLLA powder layer by layer.Dynamic socking method was used to
study the in vitro release characteristics,and cell culture experiment was used
to test the cytocompatibility of the implant.Results PLLA slow-release implants
were made by using the PLLA powder as matrix and isoniazid/rifampicin organic
solvent as binding liquid through 3D printing.The drugs in the implants
distributed in nest under electron microscope.The concentrations of both drugs
were still higher than the lowest effective bacteriostasis concentration after
release for 32 days.Cytotoxicity and direct contact tests indicated that the
implants had rare cytotoxicity and favorable biocompatibility. Conclusion The
donut-shaped implants can be successfully fabricated using the 3D printing
method,which offers a new method for the manufacturing of topical slow-release
anti-tuberculosis drugs.
PMID- 29338817
TI - Correlation of Stress Hyperglycemia after Ischemic Stroke with Early Vascular
Cognitive Impairment.
AB - Objective To investigate the influence and forecast value of stress hyperglycemia
on the early vascular cognitive impairment (VCI) in stroke patients.Methods
Totally 422 patients with acute non-diabetic stroke were divided into three
groups according to the fasting plasma glucose level:the euglycemia group (<6.1
mmol/L),the mild stress hyperglycemia group (6.1-7.0 mmol/L),and the severe
stress hyperglycemia group (>=7.0 mmol/L).Mini-mental state
examination,Alzheimer's disease rating scale cognitive subscale,and clinical
dementia rating scale were used to evaluate early cognition in post-stroke
patients,and patients were divided into three groups accordingly:normal cognitive
function group,mild VCI group,and vascular dementia group.Correlation analysis
was carried out on the level of stress hyperglycemia and the degree of
VCI.Results Of these 422 patients,stress hyperglycemia was identified in 62 cases
(14.7%).The risk of stress hyperglycemia was higher in patients with a high
degree of education [(8.39+/-3.85)years vs.(6.62+/-4.39)years,P=0.037)] or a
history of cardiovascular disease (45.2% vs.18.3%,P=0.001).VCI was detected in
270 patients (64.0%).Age,sex,smoking,National Institute of Health Stroke Scale
score,Hamilton Depression Rating Scale score,stress hyperglycemia,and history of
cardiovascular disease were related with early VCI after non-diabetic ischemic
stroke (P<0.05).Multivariate Logistic regression analysis showed that stress
hyperglycemia was an independent risk factor for VCI in patients with non
diabetic ischemic stroke (OR=3.086,95% CI=1.065-8.929).The risks of cognitive
impairment in the mild stress hyperglycemia group and the severe stress
hyperglycemia group were higher than that of the euglycemia group,while it was
also higher in the severe stress hyperglycemia group than in the mild stress
hyperglycemia group (61.11% vs.75.00% vs.90.91%).Stress hyperglycemia was
positively correlated with the high risk of early cognitive impairment in stroke
patients (rs=0.185,P=0.007).Conclusion There is a significant correlation between
stress hyperglycemia and early VCI after ischemic stroke.
PMID- 29338818
TI - Expression and Function of Long Non-coding RNA CASC19 in Colorectal Cancer.
AB - Objective To investigate the expression, function and significance of long non
coding RNA (lncRNA) CASC19 in colorectal cancer (CRC). Methods Real-time
quantitative polymerase chain reaction was employed to determine the expression
of CASC19 in 40 paired samples from CRC surgical specimens and 5 CRC cell lines.
The correlations of CASC19 expression with clinicopathologic parameters were
analyzed. Transwell assay was applied to detect the migration ability of CRC
cells after the CASC19 expression was knocked down by small interfering RNA.
Results The expression of CASC19 in colorectal cancer was significantly higher
than those in adjacent normal mucosa tissues (t=5.527, P<0.000 1) and was
associated with metastasis (P=0.044). Knockdown of CASC19 expression in CRC
inhibited the migration ability of CRC in vitro. Conclusions The expression of
CASC19 increases in CRC. CASC19 expression is not associated with age, gender, or
tumor site/differentiation but with tumor size, lymph node metastasis, and
distant metastasis, suggesting high CASC19 expression may promote CRC metastasis.
PMID- 29338819
TI - In Vitro Efficacy of Continuous Mild High Temperature on the Biofilm Formation of
Aspergillus Niger.
AB - Objective To investigate whether continuous mild high temperature (increased
temperature without causing significant damage to host cells) can inhibit the
biofilm formation of Aspergillus niger (A.niger) and its vitality.Methods A.niger
biofilms were formed on a coverslip in 24-well tissue culture plate and were
checked at the time points 4,8,10,16,24,48 and 72 hours.Confocal laser scanning
microscopy (CLSM) was used to image and quantify A.niger biofilm formation under
three different continuous mild high temperatures at 37C,39C,and
41C.Furthermore,2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5
carboxanilide (XTT) assay was used to quantify the dynamic growth of A.niger
biofilm under the above conditions.Results Compared with the culture condition
37C,CLSM analysis at 39C or 41C showed that higher temperature induced later
germination at 4 hours (t=8.603,P=0.047;t=14.550,P=0.008),poorer hyphal
elongation at 8 hours(t=35.118,P=0.039;t=63.450,P=0.006),poorer polar growth,and
reduced biofilm thickness from 10 to 24 hours.The XTT assay showed that higher
temperature (39C or 41C) lead to lower vitality at 10 hours,higher vitality at 16
hours,but finally lower vitality from 24 to 72 hours
(t=24.262,P=0.038;t=7.556,P=0.031).Conclusion Continuous mild high temperature
may have a negative regulatory effect on biofilm formation of A.niger and its
vitality.
PMID- 29338820
TI - Preoperative Evaluation of the Grade and Stability of Osteochondritis Dissecans
of the Knee by Magnetic Resonance Imaging.
AB - Objective To assess the diagnostic performance of magnetic resonance imaging
(MRI) in the grading of osteochondritis dissecans (OCD) of the knee.Methods
Totally 47 patients with OCD of the knee confirmed by arthroscopy were
retrospectively enrolled in this study.The OCD lesions were classified into four
stages according to classification system of the International Cartilage Repair
Society.Two radiologists analyzed all MRI findings independently,and the results
were compared with those of arthroscopy.Sensitivity,specificity,and accuracy were
calculated.Kappa value were calculated to quantify inter-observer agreement of
the diagnostic OCD grade between two doctors by MRI.Specificity,sensitivity,and
accuracy of MRI criteria indicating instability for detection of OCD instability
were calculated.Results Of these 47 patients with 48 OCD lesions,stages
I,II,III,and III lesions were detected in 4,8,16,and 20 patients,respectively.The
specificity,sensitivity,and accuracy for the diagnosis of OCD stability were
75.0% (83.3%),88.9% (86.1%),and 85.4% (85.4%) for observer l (2),and the
agreement of OCD grade between these two readers was substantial with a Kappa
value of 0.82.The specificity,sensitivity,and accuracy of MRI criteria for the
detection of OCD instability including high T2 signal intensity at the interface
between the OCD and the underlying bone,multiple cysts or a single cyst of>5 mm
in diameter surrounding OCD lesions,high T2 signal intensity cartilage fracture
line traversing the articular cartilage,and osteochondral defect were
83.3%,80.6%,and 81.3%;75.0%,72.2%,and 72.9%;66.7%,69.4%,and 68.8%;100%,86.1%,and
89.6%,respectively. Conclusions Osteochondral defect is the most specific MRI
sign for diagnosing instable OCD of the knee,whereas osteochondral fracture line
has the lowest accuracy.MRI is a useful method to evaluate the grade and
stability of OCD of the knee.
PMID- 29338821
TI - Factors Influencing Regional Cerebral Oxygen Saturation during One-lung
Ventilation in Thoracic Surgery.
AB - Objective To identify factors influencing regional cerebral oxygen saturation
(rScO2) during one-lung ventilation (OLV) in thoracic surgery. Methods Totally 33
patients with an ASA physical status of 1-3 scheduled for elective thoracic
surgery with one-lung ventilation under general anesthesia were recruited. After
anesthesia was induced with propofol,fentanyl/sufentanil,and rocuronium. All
patients received balanced anesthesia using sevoflurane. During OLV,volume
controlled ventilation was used with a tidal volume of 6-7 ml/kg and an
inspiration:expiration ratio of 1:1.5. The ventilator frequency was adjusted with
a target end-tidal carbon dioxide partial pressure (PetCO2) between 35 mmHg and
45 mmHg. During the anesthesia,patients were maintained at a pulse oxygen
saturation (SpO2) of>90%,systolic blood pressure (SBP) of>90 mmHg (or reducing no
more than 30% of the basic values),heart rate (HR) of>50 beat/min,and hemoglobin
concentration of>90 g/L. Changes of rScO2 were monitored with FORESIGHT probes by
specialized researchers. Patients were classified into low rScO2 (L-rScO2) group
(n=10) or high rScO2 (H-rScO2)group(n=23) according to whether the lowest
intraoperative rScO2 was under 65% or 15% lower than the baseline values. We
compared gender,age,body mass index (BMI),intraoperative hemoglobin level,and the
values of peak airway pressure (Ppeak),SBP,PetCO2,and SpO2 when rScO2 dropped to
the lowest level between these two groups. Results Statistically higher Ppeak and
lower SBP were noted in the L-rScO2 group compared with H-rScO2 group
(P=0.028,P=0.046). SpO2 was lower in the L-rScO2 group compared with H-rScO2
group,but the difference was not statistically significant (P=0.421). There was
also no significant difference between the two groups according to
age,BMI,SpO2,PetCO2,or hemoglobin level. Ppeak appeared to be a risk factor for
rScO2 reduction during OLV,as shown by unconditioned Logistic regression
analysis. Conclusion During OLV in thoracic surgery,Ppeak is a risk factor for
rScO2 reduction.
PMID- 29338822
TI - Assessment of Early Clopidogrel Therapy Use among Acute Myocardial Infarction
Patients in Central-rural China in 2006 and 2011.
AB - Objective To explore the application and influencing factors of early clopidogrel
use in patients with acute myocardial infarction (AMI) in the central-rural
region of China in 2006 and 2011. Methods A representative sample of patients in
central-rural region of China admitted to hospital for AMI was created from a two
stage random sampling. In the first phase,a simple random-sampling procedure was
used to identify participating hospitals. In the second stage,we selected
patients admitted to each participating hospitals for AMI with a systematic
sampling approach. Then we obtained clinical information via central medical
record abstraction for each patient. For analysis of early clopidogrel therapy
(within 24 hours of admission) status,we used multilevel Logistical regression
models with the use of generalized estimating equations. Results We identified
1464 patients eligible for early clopidogrel therapy. From 2006 to 2011,the early
application rate of clopidogrel increased significantly,from 3.98% to 48.72%
(P<0.0001). Logistic regression analysis showed that patients with hypertension
were more likely to receive early clopidogrel(OR=1.65,95% CI=1.21
2.26,P=0.001),smokers were associated with greater likelihood to receive early
clopidogrel(OR=1.87,95% CI=1.19-2.95,P=0.007),and patients with chest discomfort
during hospitalization indicated association with higher likelihood of early
clopidogrel use within 24 hours of admission (OR=2.17,95% CI=1.35-3.49,P=0.001).
Conclusions Early clopidogrel use in AMI patients has been improved from 2006 to
2011. However,tremendous gap still exists between guidelines and clinical
practice. Quality improvement initiatives are in urgent need to support further
improvements in early clopidogrel use for AMI patients.
PMID- 29338823
TI - Relationship of Methylation within Upper Stream Region of Transcription Starts
Site of HOXA5 Gene with Neural Tube Defects.
AB - Objective To investigate the relationship between the methylation level of
transcription starts site (TSS) upper stream of homeobox gene and the neural tube
defects (NTDs). Methods A case-control study of two stages was designed. In the
first stage,10 cases and 8 controls were extracted,in whom Illumina Infinium
Human Methylation 450 k genome-wide beadchip was used for the quantification of
DNA methylation levels of brain and spinal tissue. In the second
stage,differentially methylated region within HOXA5 gene was detected with a
larger numbers of samples (52 cases and 23 controls). DNA of brain or spinal
tissue was extracted,and Matrix-assisted laser desorption ionization time-of
flight mass spectrometry technique of MassARRAY platform was employed for the
validation of differentially methylated region of HOXA5 gene. Results In the
first stage,27 CpG sites within TSS region of HOXA5 gene were found to be
significantly hyper-methylated in case group compared to control group (P<0.05).
In the second stage,a total of 10 CpG sites were analyzable within the
differentially methylated region in the first stage. In the NTD case group,spinal
bifida subgroup,and anencephaly subgroup,there were 7,6,and 2 sites with
significantly higher methylation levels than that of control group (P<0.05). The
average methylation level of TSS upper stream region within HOXA5 gene was higher
in case group than control group [case group:(31.3+/-13.9)%,control group:(21.4+/
9.7)%],and the odds ratio after adjusting gender of fetus and pregnant week was
1.09 (1.03-1.16). Conclusion Hypermethylation within TSS upper stream region of
HOXA5 gene in fetus is associated with a higher risk of NTDs.
PMID- 29338824
TI - Effects of Preoperative Isokinetic Eccentric Training and Whey Protein Isolate
Supplement on Quadriceps Strength and Knee Function in Patients with Anterior
Cruciate Ligament Rupture.
AB - Objective To explore the effect of preoperative isokinetic eccentric training
with or not whey protein isolate supplement before operation on lower limb muscle
strength and knee function in patients with anterior cruciate ligament (ACL)
rupture. Methods A total of 22 male volunteers aged 18-40 years with ACL rupture
were recruited in outpatient service. With randomized block design,subjects were
randomly assigned to isokinetic eccentric training (IE) group and isokinetic
eccentric training with whey protein isolate supplement (IE+WPI) group. The IE
group received isokinetic eccentric training of the injured limb on an isokinetic
dynamometer under the guidance of physiatrist in laboratory before operation.
There were 3-4 sets per day with 8-10 repetitions for each set,twice a week,with
at least one day between sessions. The IE+WPI group were supplied with whey
protein isolate 22 g per day on the basis of isokinetic eccentric training,taking
breakfast or 30-60 minutes after the training. The intervention lasted for 6
weeks. Isokinetic muscle strength of limbs,the function and laxity of knee,the
circumferences of thigh and knee,and the body composition were measured before
and after the treatment. Results Compared with baseline,the peak torque (PT) of
isokinetic-eccentric contraction (IE group:41.0%,P=0.018;IE+WPI
group:46.7%,P=0.008) and the concentric contraction (IE
group:29.6%,P=0.018;IE+WPI group:38.9%,P=0.038) of quadriceps in the two training
groups significantly increased after isokinetic eccentric training. The Lysholm
score increased significantly in IE+WPI group compared with baseline (P=0.018).
Conclusions Isokinetic eccentric training before operation for ACL rupture
patients can increase the strength of quadriceps and improve the function of
knees. Protein isolate supplement can improve such effect.
PMID- 29338825
TI - Efficacy of Rituximab for Patients with Chronic Lymphocytic Leukemia.
AB - Objective To evaluate the efficacy of rituximab in treating chronic lymphocytic
leukemia (CLL). Methods The clinical data of CLL patients receiving
fludarabine,cyclophosphamide+/-rituximab (with or without rituximab) regimen or
cyclophosphamide,vincristine,and prednisone+/-doxorubicin+/-rituximab regimen in
our hospital from March 2000 to February 2015 were analyzed retrospectively.
Therapeutic efficacies and survivals of patients treated with different regimens
were evaluated and compared. Results The complete response (CR) rate and the
overall response rate (ORR) in 72 patients (43.6%) treated with rituximab were
significantly higher than those treated without rituximab (38.9% vs.
21.5%,P=0.015;83.3% vs. 60.2%,P=0.001). The median PFS and OS for patients
treated with rituximab were 53.0 (27.0-79.0) months and 112.0 (81.1-142.9)
months,and the median PFS and OS for patients treated without rituximab were 28.0
(18.3-37.7) months and 89.0(72.0-106.0),but the results were not statistically
significant (P=0.094,P=0.109). According to the cytogenetic features,patients
were further divided into high-risk subgroup (with chromosome 17p deletion or 11q
deletion) and non-high-risk subgroup. And in the high-risk subgroup,the ORR of
patients treated with rituximab was 86.4%,which was significantly higher than
that in patients treated without rituximab (53.3%)(P=0.012);in the non-high-risk
subgroup,the PFS was marginally prolonged in patients treated with rituximab,but
the difference was not statistically significant(P=0.050). Conclusions Compared
with traditional chemotherapy,the chemoimmunotherapies with rituximab result in
higher CR rate and ORR in CLL patients. In patients without 17p deletion or 11q
deletion,the use of rituximab can marginally prolong PFS.
PMID- 29338826
TI - Application of the Dual-layer Spectral Detector CT in the CT Angiography of
Superior Vena Cava.
AB - Objective To evaluate the application of the dual-layer spectral detector CT in
the CT angiography of superior vena cava (SVC). Methods Totally 30 consecutive
patients who underwent chest enhanced CT in our center were enrolled in this
study. Eight series of images were reconstructed,including the conventional
images at 120 kVp and seven series of virtual monoenergetic spectral images at
40,50,60,70,80,90,and 100 keV. The regions of interest (ROIs) were placed at the
level of the proximal end,middle part,and distal end in the SVC vessel. The CT
values and standard deviations of these three ROIs and the lipid on prothroax
wall were measured. The signal to noise ratio (SNR),contrast to noise ratio
(CNR),and effective dose (ED) were calculated. In addition,the quality of images
was evaluated by two blinded readers using a grading scheme. The differences in
CT values,SNR,and CNR among groups were analyzed using the independent t-test.
The quality of all images was compared using non-parametric test between two
readers,and the consistency between two radiologists were evaluated by using
Kappa (kappa) value. Results There was no significantly different attenuation
value among three ROIs of the SVC for each monoenergetic images (all P>0.05). The
SVC showed significantly higher attenuation value (223.51+/-40.35)HU,SNR 13.56+/
4.18 and CNR 24.15+/-6.58 in the 40 keV group than in other keV groups and the
conventional group [attenuation value:(97.70+/-13.85)HU;SNR:4.59+/
1.41;CNR:9.69+/-2.81] (P<0.005). The mean ED was(2.04+/-0.63) mSv. The subjective
diagnostic scores accessed from two radiologists were 1 (1,2) and 1 (1,2) (Z=
0.358,P=0.720). The subjective diagnostic quality values evaluated by two
observers showed excellent consistency (kappa=0.863,P=0.000). Conclusion An
optimal imaging of the SVC can be achieved on monoenergetic reconstructions at 40
keV by using the dual-layer spectral detector CT.
PMID- 29338827
TI - Risk Factors of Intrauterine Adhesion after Hysteroscopic Resection of
Endometrial Polyps.
AB - Objective To analyze the risk factors of intrauterine adhesion (IUA) after
hysteroscopic resection of endometrial polyps. Methods Totally 359 patients
undergoing hysteroscopic resection of endometrial polyps from January 2013 to
December 2016 were enrolled in this study. The clinical data of IUA group and non
IUA group were compared. Univariate analysis was performed to identify the risk
factors of IUA,and multivariate Logistic regression analysis was further
performed to get the independent risk factors. Results Of these 359 patients,IUA
occured after operation in 56 patients (15.60%). Univariate analysis showed
underlying diseases (chi2=7.381,P=0.004),multiple polyps
(chi2=3.376,P=0.040),uterus with uterine fibroids or endometrial hyperplasia
(chi2=6.495,P=0.009),history of curettage(chi2=31.576,P=0.000),pelvic infection
(chi2=8.582,P=0.001),intrauterine device (chi2=7.161,P=0.006),history of cesarean
section (chi2=5.493,P=0.014),and multigravida were (chi2=16.886,P=0.000) the risk
factors of IUA. Logistic regression analysis showed other diseases of
uterus(chi2=19.542,P=0.026),history of curettage (chi2=29.614,P=0.000),pelvic
infection (chi2=5.627,P=0.002),intrauterine device (chi2=11.342,P=0.08),history
of cesarean section(chi2=8.549,P=0.035),and multigravida (chi2=15.493,P=0.000)
were the independent risk factors of IUA after hysteroscopic resection of
endometrial polyps. Conclusion Other diseases of uterus,history of
curettage,pelvic infection,intrauterine device,history of cesarean section,and/or
multigravida can increase the risk of IUA after hysteroscopic resection of
endometrial polyps.
PMID- 29338828
TI - Screening Serum Differential Proteins for Childhood Asthma at Different Control
Levels by Isobaric Tags for Relative and Absolute Quantification-based Proteomic
Technology.
AB - Objective To screen serum differential proteins for childhood asthma at different
control levels,which provided the basis for the prevention and treatment of
childhood asthma. Methods Isobaric tags for relative and absolute
quantification,two-dimensional liquid chromatography,nanoelectrospray
ionization,and high-resolution tandem mass spectrometry using the hybrid
quadrupole time-of-flight platform was used to screen the differential proteins
in serum samples from pediatric patients with controlled,partly controlled,or
uncontrolled childhood asthma. Differential proteins were validated using enzyme
linked immunosorbent assay (ELISA). Results A total of 260 expressed proteins
were identified. Among them 57 differentially expressed proteins were found among
the different control levels of childhood asthma (fold<0.8 or fold>1.2). The
differentially expressed proteins were involved mainly in 21 biological processes
and 8 molecular functions and were located in 17 cellular components. ELISA
showed that the serum vitronectin level was significantly higher in controlled
group [(573.92+/-412.43) MUg/ml] than in uncontrolled group[(382.27+/
238.64)]MUg/ml (P=0.0399). Conclusion We identified 57 differential proteins for
childhood asthma at different control levels,which may be used as potential
biological targets for the control of childhood asthma.
PMID- 29338829
TI - Imaging Findings of Common Opportunistic Infections and Malignant Tumors in
Acquired Immunodeficiency Syndrome Patients.
AB - The incidence of human immunodeficiency virus (HIV) infection has gradually
increased in recent years.HIV mainly destroys the body's immune system,leading to
decreased body resistance and thus the development of a variety of opportunistic
infections and neoplastic diseases,especially in the digestive system.
However,the clinical manifestations,laboratory findings,and physical examination
results of these conditions are not specific. Imaging examinations can determine
the presence of infection and tumor lesions and the disease
scope;furthermore,they are useful tools for biopsy and follow-up evaluation. A
better knowledge of the radiological findings of these diseases can enable
radiologists to provide more information to patients and clinicians. This article
summarize the imaging findings of common opportunistic infections and malignant
tumors in acquired immunodeficiency syndrome patients.
PMID- 29338830
TI - Application of Cardiopulmonary Exercise Testing in Enhanced Recovery after
Surgery.
AB - Enhanced recovery after surgery (ERAS) is a new perioperative concept that aims
to reduce perioperative stress response and accelerate rehabilitation of patients
through a variety of optimized management. With the wider application of this
concept,the effective implementation of ERAS program has become a new challenge.
Cardiopulmonary exercise testing (CPET) has shown promising value in the
preoperative assessment,perioperative optimization,and postoperative
rehabilitation of ERAS. This article reviews the application of CPET in ERAS,with
an attempt to provide evidence for more detailed and comprehensive ERAS program.
PMID- 29338831
TI - Diagnosis and Treatment of Acute Intermittent Porphyria.
AB - Acute intermittent porphyria (AIP) is a metabolic disease caused by hepatic
deficiency of hydroxymethylbilane synthase. Its clinical manifestations include
acute abdominal pain,neuropsychological abnormalities,and red urine. Due to its
low incidence and varied clinical symptoms,the rates of misdiagnosis and
mistreatment were particularly high. Biochemical testing and gene detection
contribute to diagnosis. Management strategies include intravenous administration
of human haemin,carbohydrate loading and symptomatic treatment.
PMID- 29338832
TI - Exhaled Air Molecules and Chronic Obstructive Pulmonary Disease.
AB - Chronic airway inflammation,a main pathologic process of chronic obstructive
pulmonary disease (COPD),can trigger inflammation cells and airway structure
cells to produce bioactive molecules,which play key roles in the pathogenesis of
COPD and are also an efficient indicators for the diagnosis and treatment of
COPD. This article reviews the important roles of these exhaled air molecules in
the diagnosis and treatment of COPD,with an attempt to offer new strategies in
the management of COPD.
PMID- 29338833
TI - Clinical Application and Development of Near-infrared Spectroscopy for Monitoring
Regional Cerebral Oxygen Saturation.
AB - The near-infrared spectroscopy has been applied to the continuous and noninvasive
monitoring of regional cerebral oxygen saturation,providing information about the
equilibrium between cerebral oxygen supply and consumption. This article reviews
the mechanism,clinical application,and limitations of this technique.
PMID- 29338834
TI - Advances in Tissue-engineered Oral Mucosa.
AB - The large defect of oral and maxillofacial region doesn't only affect the
function and aesthetics but also has an adverse impact on patients' psychology.
The traditional way to restore the defects are limited by donor site and
secondary trauma. In recent years,the oral mucosal tissue engineering has
developed rapidly and provides a new solution for craniofacial reconstruction.
Tissue-engineered oral mucosa is an ideal substitute of oral mucosa. It can be
used in clinical settings and in vitro experiments. This articles review the
recent advances in tissue-engineered oral mucosa and its applications.
PMID- 29338835
TI - General health, wellbeing and oral health of patients older than 75 years
attending health assessments.
AB - Annual health assessments by general practices for community-dwelling people aged
75 years and over are important for the early intervention and monitoring of
chronic health conditions, including oral disease. Uptake of the health
assessment to date has been poor, and little is known of the general and oral
health profile of patients. Older patients attending health assessments at
general practices in South Australia were sampled for this study. Data on
demographic and socioeconomic characteristics, and patients' general and oral
health, were collected by mailed questionnaire from 459 respondents. By
comparison with national estimates, patients attending health assessments fared
worse in many of the measures, such as self-rated general health, quality of life
and the prevalence of most chronic conditions, as well as their socioeconomic
circumstances. Also identified were a high degree of nutritional risk and clear
need for oral health treatment, with poor self-rated oral health being three-fold
higher than the national age-eligible population. Patients attending health
assessments would likely benefit from nutritional screening (by a validated tool)
and specific assessment of their oral health and dentition, supported by
appropriate referral or intervention.
PMID- 29338836
TI - Systems levers for commissioning primary mental healthcare: a rapid review.
AB - Primary Health Networks (PHNs) are a new institution for health systems
management in the Australian healthcare system. PHNs will play a key role in
mental health reform through planning and commissioning primary mental health
services at a regional level, specifically adopting a stepped care approach.
Selected PHNs are also trialling a healthcare homes approach. Little is known
about the systems levers that could be applied by PHNs to achieve these aims. A
rapid review of academic and grey literature published between 2006 and 2016 was
undertaken to describe the use of systems levers in commissioning primary care
services. Fifty-six documents met the inclusion criteria, including twelve
specific to primary mental healthcare. Twenty-six levers were identified.
Referral management, contracts and tendering processes, and health information
systems were identified as useful levers for implementing stepped care
approaches. Location, enrolment, capitation and health information systems were
identified as useful in implementing a healthcare homes approach. Other levers
were relevant to overall health system functioning. Further work is needed to
develop a robust evidence-base for systems levers. PHNs can facilitate this by
documenting and evaluating the levers that they deploy, and making their findings
available to researchers and other commissioning bodies.
PMID- 29338837
TI - Stromule extension along microtubules coordinated with actin-mediated anchoring
guides perinuclear chloroplast movement during innate immunity.
AB - Dynamic tubular extensions from chloroplasts called stromules have recently been
shown to connect with nuclei and function during innate immunity. We demonstrate
that stromules extend along microtubules (MTs) and MT organization directly
affects stromule dynamics since stabilization of MTs chemically or genetically
increases stromule numbers and length. Although actin filaments (AFs) are not
required for stromule extension, they provide anchor points for stromules.
Interestingly, there is a strong correlation between the direction of stromules
from chloroplasts and the direction of chloroplast movement. Stromule-directed
chloroplast movement was observed in steady-state conditions without immune
induction, suggesting it is a general function of stromules in epidermal cells.
Our results show that MTs and AFs may facilitate perinuclear clustering of
chloroplasts during an innate immune response. We propose a model in which
stromules extend along MTs and connect to AF anchor points surrounding nuclei,
facilitating stromule-directed movement of chloroplasts to nuclei during innate
immunity.
PMID- 29338839
TI - Ultrasound Assessment of a Subcutaneous Eumycetoma of the Eyebrow in an
Immunocompromised Patient.
PMID- 29338840
TI - Hydrogen sulfide provides intestinal protection during a murine model of
experimental necrotizing enterocolitis.
AB - BACKGROUND: Necrotizing enterocolitis (NEC) continues to be a morbid surgical
condition among preterm infants. Novel therapies for this condition are
desperately needed. Hydrogen sulfide (H2S) is an endogenous gasotransmitter that
has been found to have beneficial properties. We therefore hypothesized that
intraperitoneal injection of various H2S donors would improve clinical outcomes,
increase intestinal perfusion, and reduce intestinal injury in an experimental
mouse model of necrotizing enterocolitis. METHODS: NEC was induced in five-day
old mouse C57BL/6 mouse pups through maternal separation, formula feeding, and
intermittent hypoxic and hypothermic stress. The control group (n=10) remained
with their mother and breastfed ad lib. Experimental groups (n=10/group) received
intraperitoneal injections of phosphate buffered saline (PBS) vehicle or one of
the following H2S donors: (1) GYY4137, 50mg/kg daily; (2) Sodium sulfide (Na2S),
20mg/kg three times daily; (3) AP39, 0.16mg/kg daily. Pups were monitored for
weight gain, clinical status, and intestinal perfusion via transcutaneous Laser
Doppler Imaging (LDI). After sacrifice on day nine, intestinal appearance and
histology were scored and cytokines were measured in tissue homogenates of
intestine, liver, and lung. Data were compared with Mann-Whitney and p<0.05 was
considered significant. RESULTS: Clinical score and weight gain were
significantly improved in all three H2S-treated groups as compared to vehicle
(p<0.05 for all groups). Intestinal perfusion of the vehicle group was 22% of
baseline while the GYY4137 group was 38.7% (p=0.0103), Na2S was 47.0% (p=0.0040),
and AP39 was 43.0% (p=0.0018). The vehicle group had a median histology score of
2.5, while the GYY4137 group's was 1 (p=0.0013), Na2S was 0.5 (p=0.0004), and
AP39 was 0.5 (p=0.0001). Cytokine analysis of the intestine of the H2S-treated
groups revealed levels closer to breastfed pups as compared to vehicle (p<0.05
for all groups). CONCLUSION: Intraperitoneal administration of H2S protects
against development of NEC by improving mesenteric perfusion, and by limiting
mucosal injury and altering the tissue inflammatory response. Further
experimentation is necessary to elucidate downstream mechanisms prior to clinical
implementation.
PMID- 29338838
TI - Neuronal populations in the occipital cortex of the blind synchronize to the
temporal dynamics of speech.
AB - The occipital cortex of early blind individuals (EB) activates during speech
processing, challenging the notion of a hard-wired neurobiology of language. But,
at what stage of speech processing do occipital regions participate in EB? Here
we demonstrate that parieto-occipital regions in EB enhance their synchronization
to acoustic fluctuations in human speech in the theta-range (corresponding to
syllabic rate), irrespective of speech intelligibility. Crucially, enhanced
synchronization to the intelligibility of speech was selectively observed in
primary visual cortex in EB, suggesting that this region is at the interface
between speech perception and comprehension. Moreover, EB showed overall enhanced
functional connectivity between temporal and occipital cortices that are
sensitive to speech intelligibility and altered directionality when compared to
the sighted group. These findings suggest that the occipital cortex of the blind
adopts an architecture that allows the tracking of speech material, and therefore
does not fully abstract from the reorganized sensory inputs it receives.
PMID- 29338841
TI - The Starch Utilization System Assembles around Stationary Starch-Binding
Proteins.
AB - Bacteroides thetaiotaomicron (Bt) is a prominent member of the human gut
microbiota with an extensive capacity for glycan harvest. This bacterium
expresses a five-protein complex in the outer membrane, called the starch
utilization system (Sus), which binds, degrades, and imports starch into the
cell. Sus is a model system for the many glycan-targeting polysaccharide
utilization loci found in Bt and other members of the Bacteroidetes phylum. Our
previous work has shown that SusG, a lipidated amylase in the outer membrane,
explores the entire cell surface but diffuses more slowly as it interacts with
starch. Here, we use a combination of single-molecule tracking, super-resolution
imaging, reverse genetics, and proteomics to show that SusE and SusF, two
proteins that bind starch, are immobile on the cell surface even when other
members of the system are knocked out and under multiple different growth
conditions. This observation suggests a new paradigm for protein complex
formation: binding proteins form immobile complexes that transiently associate
with a mobile enzyme partner.
PMID- 29338842
TI - Real-Time Nanopore-Based Recognition of Protein Translocation Success.
AB - A growing number of new technologies are supported by a single- or multi-nanopore
architecture for capture, sensing, and delivery of polymeric biomolecules.
Nanopore-based single-molecule DNA sequencing is the premier example. This method
relies on the uniform linear charge density of DNA, so that each DNA strand is
overwhelmingly likely to pass through the nanopore and across the separating
membrane. For disordered peptides, folded proteins, or block copolymers with
heterogeneous charge densities, by contrast, translocation is not assured, and
additional strategies to monitor the progress of the polymer molecule through a
nanopore are required. Here, we demonstrate a single-molecule method for direct,
model-free, real-time monitoring of the translocation of a disordered,
heterogeneously charged polypeptide through a nanopore. The crucial elements are
two "selectivity tags"-regions of different but uniform charge density-at the
ends of the polypeptide. These affect the selectivity of the nanopore differently
and enable discrimination between polypeptide translocation and retraction. Our
results demonstrate exquisite sensitivity of polypeptide translocation to applied
transmembrane potential and prove the principle that nanopore selectivity reports
on biopolymer substructure. We anticipate that the selectivity tag technique will
be broadly applicable to nanopore-based protein detection, analysis, and
separation technologies, and to the elucidation of protein translocation
processes in normal cellular function and in disease.
PMID- 29338844
TI - SFE/SFEDP adrenal insufficiency French consensus: Introduction and handbook.
AB - The French endocrinology society (SFE) and the French pediatric endocrinology
society (DFSDP) have drawn up recommendations for the management of primary and
secondary adrenal insufficiency in the adult and child, based on an analysis of
the literature by 19 experts in 6 work-groups. A diagnosis of adrenal
insufficiency should be suspected in the presence of a number of non-specific
symptoms except hyperpigmentation which is observed in primary adrenal
insufficiency. Diagnosis rely on plasma cortisol and ACTH measurement at 8am
and/or the cortisol increase after synacthen administration. When there is a
persistant doubt of secondary adrenal insufficiency, insulin hypoglycemia test
should be carried out in adults, adolescents and children older than 2 years. For
determining the cause of primary adrenal insufficiency, measurement of anti-21
hydroxylase antibodies is the initial testing. An adrenal CT scan should be
performed if auto-antibody tests are negative, then assay for very long chain
fatty acids is recommended in young males. In children, a genetic anomaly is
generally found, most often congenital adrenal hyperplasia. In the case of
isolated corticotropin (ACTH) insufficiency, it is recommended to first eliminate
corticosteroid-induced adrenal insufficiency, then perform an hypothalamic
pituitary MRI. Acute adrenal insufficiency is a serious condition, a
gastrointestinal infection being the most frequently reported initiating factor.
After blood sampling for cortisol and ACTH assay, treatment should be commenced
by parenteral hydrocortisone hemisuccinate together with the correction of
hypoglycemia and hypovolemia. Prevention of acute adrenal crisis requires an
education of the patient and/or parent in the case of pediatric patients and the
development of educational programs. Treatment of adrenal insufficiency is based
on the use of hydrocortisone given at the lowest possible dose, administered
several times per day. Mineralocorticoid replacement is often necessary for
primary adrenal insufficiency but not for corticotroph deficiency. Androgen
replacement by DHEA may be offered in certain conditions. Monitoring is based on
the detection of signs of under- and over-dosage and on the diagnosis of
associated auto-immune disorders.
PMID- 29338845
TI - Protocolized warfarin reversal with 4-factor prothrombin complex concentrate
versus 3-factor prothrombin complex concentrate with recombinant factor VIIa.
AB - INTRODUCTION: Life-threatening bleeding can complicate warfarin therapy. Rapid
anticoagulant reversal via replacement of vitamin-K dependent clotting factors is
essential for hemostasis. We compare two methods of rapid factor replacement for
warfarin reversal. METHODS: A retrospective cohort study of warfarin-treated
patients experiencing life-threatening bleeding who received a reversal protocol
comprised of 4F PCC or 3F PCC and rFVIIa was performed. Demographic, clinical and
anticoagulant reversal information, and all adverse events attributed to warfarin
reversal were recorded. RESULTS: 195 patients were included in final analysis.
While baseline demographics were similar between groups, the 3F-PCC group had a
longer ICU LOS and higher in-hospital mortality (p < .01, .01). Pre-reversal INR
was similar between both groups, but post-reversal INR was significantly lower in
the 3F-PCC group, 0.8 versus 1.3 (p < .01). Significantly more patients
experienced thromboembolic complications in the 3F-PCC group than the 4F-PCC
group (p < .01). Receipt of rFVIIa was significantly associated with
thromboembolic complications. DISCUSSION: A 4F PCC reversal strategy is
efficacious in INR reversal and provides lower thromboembolic risk as compared to
3F PCC with rFVIIa.
PMID- 29338846
TI - Comparison of two trunk electromagnetic sensor placement methods during shoulder
motion analysis.
AB - For kinematic studies of the shoulder, electromagnetic sensors are commonly
placed on the humerus, scapula, and trunk. The trunk sensor is used to describe
humeral and scapular kinematics with respect to the trunk. There are two common
trunk sensor placements, the sternum or third thoracic vertebrae (T3). It is
currently unclear if placement of the trunk sensor affects kinematics, making it
difficult to compare data across studies. The purpose of this study was to
compare two trunk sensor placements (T3 and sternum) on trunk and scapular
kinematics during arm elevation. An electromagnetic tracking system was used to
collect kinematic data during five consecutive repetitions of ascending and
descending arm elevation in the sagittal plane. The results indicate that trunk
sensor placement had no significant effect on trunk kinematics or scapular
upward/downward rotation and internal/external rotation. Scapular
anterior/posterior tilt was significantly greater when the trunk sensor was on
the sternum compared to the T3 vertebrae during ascending 30 degrees -120 degrees
: mean difference = -3.51 degrees (95%CI: -5.61, -1.40), and descending 120
degrees -30 degrees : mean difference = -3.27 degrees (95%CI: -6.07, -0.48).
However, the difference in anterior/posterior tilt did not exceed the error
(minimal detectable change), and thus is likely not a meaningful difference.
These results indicate the trunk sensors can be affixed on T3 or the sternum,
depending on the needs of the study.
PMID- 29338843
TI - Current Status of Animal Models of Posttraumatic Stress Disorder: Behavioral and
Biological Phenotypes, and Future Challenges in Improving Translation.
AB - Increasing predictability of animal models of posttraumatic stress disorder
(PTSD) has required active collaboration between clinical and preclinical
scientists. Modeling PTSD is challenging, as it is a heterogeneous disorder with
>=20 symptoms. Clinical research increasingly utilizes objective biological
measures (e.g., imaging, peripheral biomarkers) or nonverbal behaviors and/or
physiological responses to complement verbally reported symptoms. This shift
toward more-objectively measurable phenotypes enables refinement of current
animal models of PTSD, and it supports the incorporation of homologous measures
across species. We reviewed >600 articles to examine the ability of current
rodent models to probe biological phenotypes of PTSD (e.g., sleep disturbances,
hippocampal and fear-circuit dysfunction, inflammation, glucocorticoid receptor
hypersensitivity) in addition to behavioral phenotypes. Most models reliably
produced enduring generalized anxiety-like or depression-like behaviors, as well
as hyperactive fear circuits, glucocorticoid receptor hypersensitivity, and
response to long-term selective serotonin reuptake inhibitors. Although a few
paradigms probed fear conditioning/extinction or utilized peripheral immune,
sleep, and noninvasive imaging measures, we argue that these should be
incorporated more to enhance translation. Data on female subjects, on subjects at
different ages across the life span, or on temporal trajectories of phenotypes
after stress that can inform model validity and treatment study design are
needed. Overall, preclinical (and clinical) PTSD researchers are increasingly
incorporating homologous biological measures to assess markers of risk, response,
and treatment outcome. This shift is exciting, as we and many others hope it not
only will support translation of drug efficacy from animal models to clinical
trials but also will potentially improve predictability of stage II for stage III
clinical trials.
PMID- 29338847
TI - Evaluation and validation of musculoskeletal force feasible set indices:
Application to manual wheelchair propulsion.
AB - The aim of this work was to assess handrim wheelchair propulsion effectiveness,
related to the applied forces on the handrim, through the force feasible set. For
a given posture of the upper-limb, it represents the set of isometric forces that
can be applied on the handrim in any direction. The force feasible set was
predicted from a musculoskeletal model of the upper-limb and trunk (10 degrees of
freedom and 56 muscles). The aim of the first part of the study was to compare
the force feasible set prediction and the force currently applied on the handrim.
The second part proposes the creation of a new index called "Musculoskeletal
Postural Performance Index" (MPPI) derived from the force feasible set and its
comparison with the Mechanical Efficiency Force (MEF). These comparisons were
conducted at 60, 80, 100, 120 and 140% of the Freely Chosen Frequency at
submaximal and maximal conditions on 5 different phases of the push phase. The
values of the MPPI were significantly correlated with those of the MEF. During
the course of the push phase, the orientation of the force feasible set main axis
approached that of the measured force and the force effectiveness evaluated
through the MPPI increased.
PMID- 29338848
TI - Preoperative Bevacizumab Administration in Proliferative Diabetic Retinopathy
Patients Undergoing Vitrectomy: A Randomized and Controlled Trial Comparing
Interval Variation.
PMID- 29338849
TI - The Challenge of Blau Syndrome.
PMID- 29338850
TI - Reply.
PMID- 29338851
TI - Reply.
PMID- 29338852
TI - Simulation-based multidisciplinary team training decreases time to critical
operations for trauma patients.
AB - BACKGROUND: Simulation has been promoted as a platform for training trauma teams.
However, it is not clear if this training has an impact on health service
delivery and patient outcomes. This study evaluates the association between
implementation of a simulation based multidisciplinary trauma team training
program at a metropolitan trauma centre and subsequent patient outcomes. METHOD:
This was a retrospective review of trauma registry data collected at an 850-bed
Level 1 Adult Trauma Centre in Sydney, Australia. Two concurrent four-year
periods, before and after implementation of a simulation based multidisciplinary
trauma team training program were compared for differences in time to critical
operations, Emergency Department (ED) length of stay (LOS) and patient mortality.
RESULTS: There were 2389 major trauma patients admitted to the hospital during
the study, 1116 in the four years preceding trauma team training (the PREgroup)
and 1273 in the subsequent 4 years (the POST group). There were no differences
between the groups with respect to gender, body region injured, incidence of
polytrauma, and pattern of arrival to ED. The POST group was older (median age 54
versus 43 years, p < 0.001) and had a higher incidence of falls and assaults (p <
0.001). There was a reduction in time to critical operation, from 2.63 h (IQR
1.23-5.12) in the PRE-group to 0.55 h (IQR 0.22-1.27) in the POST-group, p <
0.001. The overall ED LOS increased, and there was no reduction in mortality.
Post-hoc analysis found LOS in ED was reduced in the cohort requiring critical
operations, p < 0.001. CONCLUSION: The implementation of trauma team training was
associated with a reduction in time to critical operation while overall ED length
of stay increased. Simulation is promoted as a platform for training teams; but
the complexity of trauma care challenges efforts to demonstrate direct links
between multidisciplinary team training and improved outcomes. There remain
considerable gaps in knowledge as to how team training impacts health service
delivery and patient outcomes. LEVEL OF EVIDENCE: Retrospective comparative
therapeutic/care management study, Level III evidence.
PMID- 29338853
TI - Atypical fractures: An issue of concern or a myth?
AB - Atypical Femoral Fractures (AFF) represent fractures located between the lesser
trochanter and the supracondylar flare of a femur. An increasing pool of evidence
supports their association with the prolonged use of bisphosphonates, even though
a direct correlation is yet to be proved. The purpose of this review is to
encapsulate the current evidence associating bisphosphonate use and the
development of AFFs, the clinical features related to their presentation, as well
as to report the armamentarium of strategies available in the prevention and
treatment of AFFs. Based on these evidence, we propose a management algorithm for
AFFs, that can serve as a guide for patients presenting with this condition.
PMID- 29338854
TI - Long-term outcomes in cancer patients who did or did not pursue fertility
preservation.
AB - OBJECTIVE: To compare long-term outcomes of cancer patients who pursued fertility
preservation (FP) with those who did not and compare random-start (RS) and
menstrual cycle-specific (CS) protocols for FP. DESIGN: Retrospective cohort.
SETTING: Single urban academic institution. PATIENT(S): Oncology patients who
contacted the FP patient navigator, 2005-2015. INTERVENTION(S): None. MAIN
OUTCOME MEASURE(S): Time to cancer treatment, disease-free survival, and
reproductive outcomes in FP versus no-FP patients and cycle outcomes for RS
versus CS protocols. Data were analyzed by chi2 and logistic regression.
RESULT(S): Of 497 patients who met the inclusion criteria, 41% elected FP. The
median number of days to cancer treatment was 33 and 19 days in the FP and no-FP
groups, respectively. There was no difference in cancer recurrence or mortality.
There were no differences in stimulation parameters, outcomes, or days to next
cancer treatment in RS versus CS protocols. Twenty-one patients returned to use
cryopreserved specimens, resulting in 16 live births. Eight of 21 returning
patients used a gestational carrier. Thirteen FP (6.4%) and 16 no-FP (5.5%)
patients experienced a spontaneous pregnancy. CONCLUSION(S): FP is both safe and
efficacious for eligible cancer patients. Only 10% of patients returned to use
cryopreserved specimens, and almost half used a gestational carrier, suggesting
the need for further research into reproductive decision-making in cancer
survivors.
PMID- 29338855
TI - Vitrified blastocyst transfer cycles with the use of only vaginal progesterone
replacement with Endometrin have inferior ongoing pregnancy rates: results from
the planned interim analysis of a three-arm randomized controlled noninferiority
trial.
AB - OBJECTIVE: To assess the noninferiority of vaginal P (Endometrin) compared with
daily intramuscular P for replacement in programmed vitrified-warmed blastocyst
transfer cycles and to assess the noninferiority of vaginal P in combination with
intramuscular progesterone every third day compared with daily intramuscular P.
DESIGN: Three-arm randomized controlled noninferiority study. To enable early
recognition of inferiority if present, an a priori interim analysis was planned
and completed once ongoing pregnancy data were available for 50% of the total
enrollment goal. The results of this interim analysis are presented here.
SETTING: Assisted reproduction technology practice. PATIENT(S): Women undergoing
transfer of nonbiopsied high quality vitrified-warmed blastocyst(s) in a
programmed cycle. INTERVENTION(S): Vitrified-warmed blastocyst transfer with mode
of P replacement determined by randomization to either: (1) 50 mg daily
intramuscular P only; (2) 200 mg twice daily vaginal Endometrin; or (3) 200 mg
twice daily Endometrin plus 50 mg intramuscular P every 3rd day. MAIN OUTCOME
MEASURE(S): Live birth. The primary outcome of this interim analysis was ongoing
pregnancy. RESULT(S): A total of 645 cycles were randomly assigned to one of the
three treatment arms, received at least one dose of P replacement therapy
according to this assignment and underwent vitrified-warmed blastocyst transfer.
These cycles were included in the intention-to-treat analysis. The study team,
including the statistician, were blinded to the identity of the treatment arms,
which were randomly labeled "A," "B," and "C" in the dataset. Ongoing pregnancy
occurred in 50%, 47%, and 31% of cycles in arms A, B, and C respectively.
Although arm C had an rate of positive hCG equivalent to the other two arms, the
rate of pregnancy loss for arm C was significantly higher than for either of the
two arms, resulting in a more than one-third lower rate of ongoing pregnancy.
There were no statistically significant differences for any outcome tested
between arms A and B. Results of a per-protocol analysis were nearly identical to
those of the intention-to-treat analysis. On completion of these analyses, arm C
was revealed to be the vaginal P only arm. CONCLUSION(S): Relative to regimens
inclusive of intramuscular P, vaginal-only P replacement for vitrified-warmed
blastocyst transfer results in decreased ongoing pregnancy, due to increased
miscarriage, and should be avoided. Randomization to the vaginal-only arm was
terminated with these findings. This trial is ongoing to assess the
noninferiority of the vaginal plus every 3rd day intramuscular P arm compared
with daily intramuscular P in terms of live birth. CLINICAL TRIAL REGISTRATION
NUMBER: NLM identifier NCT02254577.
PMID- 29338856
TI - Parental health status and infant outcomes: Upstate KIDS Study.
AB - OBJECTIVE: To assess parental health status inclusive of infertility and infant
outcomes. DESIGN: Birth cohort with cross-sectional analysis of parental health
status and infant outcomes. SETTING: Not applicable. PATIENT(S): Parents (n =
4,886) and infants (n = 5,845) participating in the Upstate KIDS birth cohort.
INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Infertility was defined as [1]
sexually active without contraception for 1+ years without pregnancy, [2] ever
requiring >=12 months to become pregnant, and [3] requiring >=12 months for index
pregnancy. Multivariable linear regression with generalized estimating equations
estimated the change (beta coefficient and 95% confidence interval [CI]) in
infant outcomes (gestation, birthweight, length, head circumference, ponderal
index) and relative to each disease, including infertility after adjusting for
age, body mass index, and infertility treatment. RESULT(S): Prevalence of
parental chronic diseases ranged from <1% to 19%, and 21% to 54% for infertility.
Maternal hypertension was negatively associated with gestation (beta, -0.64; 95%
CI, -1.03, -0.25) and birthweight (-151.98; -262.30, -41.67) as was asthma and
birthweight (-75.01; -130.40, -19.62). Maternal kidney disease was associated
with smaller head circumference (-1.09; -2.17, -0.01), whereas paternal
autoimmune disease was associated with larger head circumference (0.87; 0.15,
1.60). Infertility was negatively associated with birthweight (-62.18; -103.78,
20.58), length (-0.33; -0.60, -0.06), and head circumference (-0.35; -0.67,
0.03). CONCLUSION(S): Infertility was significantly associated with reduced
infant size even after accounting for infertility treatment, although the
magnitude of reduction varied by definition of infertility. Absence of pregnancy
within a year of being at risk may be informative about health.
PMID- 29338858
TI - Cost-effectiveness analysis in cardiac surgery: A review of its concepts and
methodologies.
PMID- 29338857
TI - Obstetric complications after frozen versus fresh embryo transfer in women with
polycystic ovary syndrome: results from a randomized trial.
AB - OBJECTIVE: To evaluate the effect of frozen embryo transfer on maternal and
neonatal complications of singleton and twin pregnancies compared with fresh
embryo transfer in women with polycystic ovary syndrome (PCOS). DESIGN: A
secondary analysis of a multicenter, randomized, controlled trial comparing live
birth after frozen vs. fresh embryo transfer (FreFro-PCOS). SETTING: Reproductive
medicine centers. PATIENT(S): A total of 1,508 patients with a diagnosis of PCOS
who were undergoing IVF were enrolled. INTERVENTION(S): On day of oocyte
retrieval, eligible patients were randomized to the fresh or frozen embryo
transfer groups. Up to two embryos were transferred in both groups. All
pregnancies were followed up until delivery. MAIN OUTCOME MEASURE(S): Gestational
diabetes mellitus, pre-eclampsia, preterm birth, small for gestational age, and
large for gestational age. RESULT(S): The risks of gestational diabetes mellitus,
preterm birth, and small for gestational age were comparable between the frozen
and fresh embryo transfer groups in both singleton and twin births. However,
singleton infants born after frozen embryo transfer were more likely to be large
for gestational age (25.2% vs. 17.5%; relative risk 1.44, 95% confidence interval
1.01-2.07, P=.044) than those born after fresh embryo transfer. Twin pregnancy
after frozen embryo transfer had a higher risk of pre-eclampsia (12.0% vs. 2.8%;
relative risk 4.31, 95% confidence interval 1.27-14.58, P=.009) than those after
fresh embryo transfer. CONCLUSION(S): In women with PCOS, frozen embryo transfer
resulted in an increased risk of large for gestational age in singleton pregnancy
and a higher risk of pre-eclampsia in twin pregnancy. CLINICAL TRIAL REGISTRATION
NUMBER: NCT01841528.
PMID- 29338859
TI - Renal function and outcome after heart transplantation.
AB - OBJECTIVES: To investigate whether measured glomerular filtration rate (mGFR) is
a risk factor for death and/or end-stage renal disease (ESRD) after heart
transplantation (HTx). METHODS: All adult patients (n = 416) who underwent HTx
between 1988 and 2010 were included. mGFR was performed both preoperatively and
postoperatively as annual follow-up. Eight patients received a concomitant kidney
transplant (KTx), and 15 underwent late KTx due to chronic renal failure after
HTx. RESULTS: The mean drop in mGFR compared with the preoperative value was 12%
during the first year after HTx. Preoperative mGFR was not predictive of
mortality or ESRD. Older or the use of a ventricular assist device (VAD) were
preoperative predictors of death. Long-term survival was significantly worse in
the patients who experienced a >25% decrease in mGFR during the first year after
transplantation. The need for acute postoperative renal replacement therapy (RRT)
was associated with impaired survival but did not predict ESRD among survivors.
On multivariable analyses, previous heart surgery, preoperative VAD, and a lower
mGFR were all predictors of RRT. In the most recent period, death without
previous ESRD was lower, and the only preoperative factors associated with ESRD
by multivariable analyses were mechanical ventilation and diabetes mellitus.
CONCLUSIONS: Pretransplantation mGFR was not predictive of mortality or ESRD
after HTx, but necessitated simultaneous or late-stage KTx in this selected
population of patients. However, patients with a decrease in >25% mGFR during the
first year post-transplantation, as well as early postoperative dialysis
dependent acute renal dysfunction, had a poor prognosis. We suggest that patients
with severely impaired kidney function, irrespective of pretransplantation renal
function, still should be considered for HTx, but also encourage careful
interpretation of our results given the selection bias involved in this
population.
PMID- 29338860
TI - Learning curve of image-guided video-assisted thoracoscopic surgery for small
pulmonary nodules: A prospective analysis of 30 initial patients.
AB - OBJECTIVES: The use of image-guided video-assisted thoracoscopic surgery for
simultaneous localization and removal of small solitary pulmonary nodules in a
hybrid operation room using C-arm cone-beam computed tomography is gaining
momentum. We sought to assess the effect of the learning curve on procedural
parameters and clinical outcomes of image-guided video-assisted thoracoscopic
surgery for treating patients with small solitary pulmonary nodules. METHODS:
Clinical variables and treatment outcomes of the 30 initial patients with
solitary pulmonary nodules who were treated with image-guided video-assisted
thoracoscopic surgery at Chang Gung Memorial Hospital (Taiwan) were prospectively
analyzed. Two sequential groups (groups I and II, n = 15 each) were compared with
regard to localization time, radiation doses, and success rates. We used the
Pearson's correlation coefficient to investigate the association between the
surgical experience and the procedural time. RESULTS: In the entire cohort, the
median size of solitary pulmonary nodules on preoperative computed tomography
images was 6 mm (interquartile range, 4.5-9 mm), and their median distance from
the pleural surface was 10 mm (interquartile range, 5-15 mm). The median tumor
depth-to-size ratio was 1.4 (interquartile range, 0.7-2.5). The clinical
parameters were similar between the 2 groups. There was an inverse association
between the surgical experience and the procedural time (Pearson's r = -0.6873; P
< .001). A significant reduction in localization time (median, 24 vs 49 minutes,
respectively; P < .001) and radiation exposure (median, 70.7 vs 224 mGy,
respectively; P < .001) was noted in group II (late patients) compared with group
I (early patients). Notably, the success rates in groups II and I were similar
(93.3% vs 86.7%, respectively; P = . 876). CONCLUSIONS: Our data demonstrate a
significant learning curve for image-guided video-assisted thoracoscopic surgery
in the treatment of solitary pulmonary nodules as evidenced by decreased
localization time and radiation exposure occurring with increased surgical
experience.
PMID- 29338861
TI - Extracorporeal membrane oxygenation before surgical repair of a postinfarction
ventricular septal defect.
PMID- 29338862
TI - New-generation stents compared with coronary bypass surgery for unprotected left
main disease: A word of caution.
AB - BACKGROUND: With the advent of bare metal stents and drug-eluting stents,
percutaneous coronary intervention has emerged as an alternative to coronary
artery bypass grafting surgery for unprotected left main disease. However,
whether the evolution of stents technology has translated into better results
after percutaneous coronary intervention remains unclear. We aimed to compare
coronary artery bypass grafting with stents of different generations for left
main disease by performing a Bayesian network meta-analysis of available
randomized controlled trials. METHODS: All randomized controlled trials with at
least 1 arm randomized to percutaneous coronary intervention with stents or
coronary artery bypass grafting for left main disease were included. Bare metal
stents and drug-eluting stents of first- and second-generation were compared with
coronary artery bypass grafting. Poisson methods and Bayesian framework were used
to compute the head-to-head incidence rate ratio and 95% credible intervals.
Primary end points were the composite of death/myocardial infarction/stroke and
repeat revascularization. RESULTS: Nine randomized controlled trials were
included in the final analysis. Six trials compared percutaneous coronary
intervention with coronary artery bypass grafting (n = 4654), and 3 trials
compared different types of stents (n = 1360). Follow-up ranged from 6 months to
5 years. Second-generation drug-eluting stents (incidence rate ratio, 1.3; 95%
credible interval, 1.1-1.6), but not bare metal stents (incidence rate ratio,
0.63; 95% credible interval, 0.27-1.4), and first-generation drug-eluting stents
(incidence rate ratio, 0.85; 95% credible interval, 0.65-1.1) were associated
with a significantly increased risk of death/myocardial infarction/stroke when
compared with coronary artery bypass grafting. When compared with coronary artery
bypass grafting, the highest risk of repeat revascularization was observed for
bare metal stents (hazard ratio, 5.1; 95% confidence interval, 2.1-14), whereas
first-generation drug-eluting stents (incidence rate ratio, 1.8; 95% confidence
interval, 1.4-2.4) and second-generation drug-eluting stents (incidence rate
ratio, 1.8; 95% confidence interval, 1.4-2.4) were comparable. CONCLUSIONS: The
introduction of new-generation drug-eluting stents did not translate into better
outcomes for percutaneous coronary intervention when compared with coronary
artery bypass grafting.
PMID- 29338863
TI - In elective arch surgery with circulatory arrest, does the arterial cannulation
site really matter? A propensity score analysis of right axillary and innominate
artery cannulation.
AB - OBJECTIVE: The preferred arterial cannulation site for elective proximal aortic
procedures requiring circulatory arrest varies, and different sites have been
tried. We evaluated the relationships between arterial cannulation site and
adverse outcomes, including stroke, in patients undergoing elective aortic arch
surgery. METHODS: We reviewed the records of 938 patients who underwent elective
hemiarch or total arch surgery with circulatory arrest between 2006 and 2016.
Five cannulation sites were used: the right axillary (n = 515; 54.9%), innominate
(n = 376; 40.1%), and right common carotid arteries (n = 15; 1.6%), each with a
side graft; the ascending aorta (n = 19; 2.0%); and the femoral artery (n = 13;
1.4%). Multivariable logistic regression analysis was used to model the effects
of cannulation site on adverse outcomes for the entire cohort and for a subcohort
of 891 patients who underwent innominate or axillary artery cannulation.
Propensity-matching yielded 564 patients (282 pairs) from the right axillary and
innominate artery groups. RESULTS: For the entire cohort, mortality, stroke, and
composite adverse outcome (operative death or persistent stroke or renal failure
at hospital discharge) rates were 7.0%, 4.1%, and 9.8%. In the multivariable
analysis of the axillary/innominate subcohort, cannulation site did not
independently predict operative mortality, persistent stroke, or composite
adverse event. These results were confirmed with the propensity-matched analysis,
where both axillary and innominate artery cannulation provided equivalent
composite adverse event rates, operative death rates, and overall stroke rates.
CONCLUSIONS: During elective arch surgery, right axillary artery cannulation and
innominate artery cannulation (both via a side graft) produce excellent results
and can be used interchangeably.
PMID- 29338864
TI - Mesothelioma: Live to fight another day.
PMID- 29338865
TI - How much can you "enhance" recovery after lung resection?
PMID- 29338866
TI - The repair of a type Ia endoleak following thoracic endovascular aortic repair
using a stented elephant trunk procedure.
AB - BACKGROUND: Type Ia endoleaks are not uncommon complications that occur after
thoracic endovascular aortic repair (TEVAR). Because aortic arch vessels prevent
extension of the landing zone, it is very difficult to manipulate a type Ia
endoleak using an extension cuff or stent-graft, especially when the aortic arch
is involved. Here, we retrospectively review our experience of surgical treatment
of type Ia endoleak after TEVAR using a stented elephant trunk procedure.
METHODS: From July 2010 to August 2016, we treated 17 patients diagnosed with a
type Ia endoleak following TEVAR using stented elephant trunk procedure. The mean
age of our patients was 52 +/- 8 years. The mean interval between TEVAR and the
open surgical repair was 38 +/- 43 months. RESULTS: All cases of type Ia endoleak
(100%) were repaired successfully. There were no in-hospital deaths. One case
required reintubation and continuous renal replacement therapy due to renal
failure; this patient recovered smoothly before discharge. One other patient
suffered a stroke and renal failure and did not fully recover following
discharge, or follow-up. During follow-up, there were 3 deaths. CONCLUSIONS:
Acceptable results were obtained using a stented elephant trunk procedure in
patients with a type Ia endoleak after TEVAR. This technique allowed us to repair
the proximal aortic arch lesions, surgically correct the type Ia endoleak, and
promote false lumen thrombosis in the distal aorta. Implantation of a stented
elephant trunk, with or without a concomitant aortic arch procedure, is an
alternative approach for this type of lesion.
PMID- 29338867
TI - Validation of a definition of excessive postoperative bleeding in infants
undergoing cardiac surgery with cardiopulmonary bypass.
AB - OBJECTIVE: To derive and validate an objective definition of postoperative
bleeding in neonates and infants undergoing cardiac surgery with cardiopulmonary
bypass. METHODS: Using a retrospective cohort of 124 infants and neonates, we
included published bleeding definitions and cumulative chest tube output over
different postoperative periods (eg, 2, 12, or 24 hours after intensive care unit
admission) in a classification and regression tree model to determine chest tube
output volumes that were associated with red blood cell transfusions and surgical
re-exploration for bleeding in the first 24 hours after intensive care unit
admission. After the definition of excessive bleeding was determined, it was
validated via a prospective cohort of 77 infants and neonates. RESULTS: Excessive
bleeding was defined as >=7 mL/kg/h for >=2 consecutive hours in the first 12
postoperative hours and/or >=84 mL/kg total for the first 24 postoperative hours
and/or surgical re-exploration for bleeding or cardiac tamponade physiology in
the first 24 postoperative hours. Excessive bleeding was associated with longer
length of hospital stay, increased 30-day readmission rate, and increased
transfusions in the postoperative period. CONCLUSIONS: The proposed standard
definition of excessive bleeding is based on readily obtained objective data and
relates to important early clinical outcomes. Application and validation by other
institutions will help determine the extent to which our specialty should
consider this definition for both clinical investigation and quality improvement
initiatives.
PMID- 29338868
TI - Survival and reoperation pattern after 20 years of experience with aortic valve
sparing root replacement in patients with tricuspid and bicuspid valves.
AB - OBJECTIVE: Remodeling or reimplantation are established operative techniques of
aortic valve-sparing root replacement. Long-term follow-up is necessary comparing
tricuspid and bicuspid aortic valves. METHODS: A total of 315 patients
(tricuspid, n = 225, bicuspid, n = 89, quadricuspid, n = 1; remodeling, n = 101,
reimplantation, n = 214) were evaluated. Mean follow-up was 10.1 +/- 5.6 and 6.4
+/- 4.2 years for the remodeling and reimplantation group, respectively. Longest
follow-up was 21.9 years with 99.2% completeness. Mean age of the patients was
55.9 +/- 14.3 for the remodeling group and 48.9 +/- 14.5 years for the
reimplantation group. RESULTS: There was no significant difference in survival
between the remodeling and reimplantation group (P = .11). Survival was
comparable with the normal population in the reimplantation group (P = .33). Risk
factors for late death were age, diabetes, and a greater New York Heart
Association classification. Cumulative incidence of reoperation at 10 years was
5.8% for the reimplantation and 11.7% for the remodeling group (P = .65).
Overall, there was no difference in the cumulative incidence of reoperation
between tricuspid and bicuspid aortic valve patients (P = .13); however, a
landmark analysis showed that in the second decade, the cumulative incidence of
reoperation was greater in bicuspid aortic valve patients (P < .001). A total of
10 of 11 reoperated bicuspid aortic valves were degenerated. CONCLUSIONS: The
remodeling and reimplantation aortic valve-sparing root replacement techniques
provided excellent long-term survival. Although the number of patients was
relatively small, we provide some hints that in the second decade after the
operation, especially in bicuspid aortic valve patients, the risk of reoperation
may be increased, needing further evaluation.
PMID- 29338869
TI - Anterior leaflet splitting during transcatheter mitral valve replacement: Killing
two birds with one stone?
PMID- 29338870
TI - Peptide retention prediction using hydrophilic interaction liquid chromatography
coupled to mass spectrometry.
AB - A model that predicts retention for peptides using a HALO(r) penta-HILIC column
and gradient elution was created. Coefficients for each amino acid were derived
using linear regression analysis and these coefficients can be summed to predict
the retention of peptides. This model has a high correlation between experimental
and predicted retention times (0.946), which is on par with previous RP and HILIC
models. External validation of the model was performed using a set of H. pylori
samples on the same LC-MS system used to create the model, and the deviation from
actual to predicted times was low. Apart from amino acid composition, length and
location of amino acid residues on a peptide were examined and two site-specific
corrections for hydrophobic residues at the N-terminus as well as hydrophobic
residues one spot over from the N-terminus were created.
PMID- 29338871
TI - Likelihood of total resolution in selective comprehensive two-dimensional liquid
chromatography with parallel processing: Simulation and theory.
AB - The probability Pr(sLC*LC) that all peaks are separated by a resolution of 1.5 or
more in selective comprehensive two-dimensional liquid chromatography (sLC * LC)
is computed for simple model systems of 5 to 60 peaks and first-dimension (1D)
gradient times of 100 to 2000 s. The computations include mimics of a commercial
instrument, whose fixed second-dimension (2D) gradient time and use of one cycle
time for initialization reduces Pr(sLC*LC) relative to an earlier report. For
serial sLC * LC, in which a single device collects and transfers 1D multiplets to
the second dimension, Pr(sLC*LC) under practical conditions is predicted to be
only slightly larger than the probability of total resolution in LC * LC for
separations of the same duration in each case. To increase Pr(sLC*LC), two model
systems are proposed based on parallel processing, in which one device collects
multiplets from the first separation while a second device simultaneously
transfers fractions from previously collected multiplets to the second dimension
for further separation. A sum of probabilities guideline is proposed by which
optimal fixed 2D gradient times, ranging from 9.5 to 12 s, are found for both
serial and parallel models. The increases of Pr(sLC*LC) based on parallel
processing are modest; the largest is only 0.062 for one system and 0.106 for the
other, relative to the serial model. A theory is derived that rationalizes the
modesty of the increase, which was unexpected. It shows that Pr(sLC*LC) equals
the probability of total resolution in the first dimension, plus the product of
the probability that all 1D multiplets are transferred to the second dimension
and the probability that all multiplets are separated in the second dimension.
The theory shows that, although parallel processing is better than serial
processing for multiplet transfer, the ability to leverage this gain is offset by
the limited probability that all multiplets are then actually separated in the
second dimension, which is only about 0.55 for conditions where the change from
serial to parallel processing is most beneficial. With these findings in hand,
two scenarios are examined for future consideration: one in which the 2D peak
capacity is doubled, and another in which multiplets are always transferred to
the second dimension. The latter shows considerable promise for increasing
Pr(sLC*LC) substantially beyond its counterpart in LC * LC. For example, a 50%
probability of separating all peaks in a 15-component mixture can be reached in
1150 s using LC * LC. The same probability can be reached in the same time for a
sample with nearly twice as many components (27) in the case of sLC * LC,
assuming transfer of all multiplets to the second dimension. These findings will
be useful to those considering systematic approaches to developing 2D-LC methods
for moderately complex mixtures, and to those interested in instrument
development for 2D-LC.
PMID- 29338872
TI - Sickle cell disease: An overview of orofacial and dental manifestations.
PMID- 29338874
TI - Extracorporeal membrane oxygenation in infants with congenital diaphragmatic
hernia.
AB - Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly which
impairs normal pulmonary development leading to acute and chronic respiratory
failure, pulmonary hypoplasia, pulmonary hypertension, and mortality. CDH is the
most common non-cardiac indication for neonatal ECMO. Prenatal and postnatal
predictors of CDH severity aid in patient selection. Centers vary in preferred
mode of ECMO and timing of CDH repair. Survivors of severe CDH with ECMO are at
risk for long-term sequelae including neurodevelopmental delays.
PMID- 29338875
TI - Computational Strategies for Exploring Circular RNAs.
AB - Recent studies have demonstrated that circular RNAs (circRNAs) are ubiquitous and
have diverse functions and mechanisms of biogenesis. In these studies,
computational profiling of circRNAs has been prevalently used as an indispensable
method to provide high-throughput approaches to detect and analyze circRNAs.
However, without an overall understanding of the underlying strategies, these
computational methods may not be appropriately selected or used for a specific
research purpose, and some misconceptions may result in biases in the analyses.
In this review we attempt to illustrate the key steps and summarize tradeoff of
different strategies, covering all popular algorithms for circRNA detection and
various downstream analyses. We also clarify some common misconceptions and put
emphasis on the fields of application for these computational methods.
PMID- 29338876
TI - Meeting report: Global vaccine and immunization research forum.
AB - Building on the success of the first Global Vaccine and Immunization Research
Forum (GVIRF), the World Health Organization, the National Institute of Allergy
and Infectious Diseases, part of the National Institutes of Health in the United
States of America, and the Bill & Melinda Gates Foundation convened the second
GVIRF in March 2016. Leading scientists, vaccine developers, and public health
officials from around the world discussed scientific advances and innovative
technologies to design and deliver vaccines as well as novel tools and approaches
to increase the uptake of vaccines throughout the world. This report summarizes
the discussions and conclusions from the forum participants.
PMID- 29338878
TI - Mostly "Old wine in new bottles." Reply to commentaries.
PMID- 29338877
TI - German travelers' preferences for travel vaccines assessed by a discrete choice
experiment.
AB - BACKGROUND: Many travelers to regions with endemic infectious diseases do not
follow health authorities' recommendations regarding vaccination against vaccine
preventable infectious diseases, before traveling. The determinants of individual
travelers' decisions to vaccinate before traveling are largely unknown. This
study aimed to provide this information using a discrete choice experiment (DCE)
administered to four types of German travelers: (1) business travelers; (2)
travelers visiting friends and relatives (VFR); (3) leisure travelers; and (4)
backpackers. METHODS: A DCE survey was developed, pretested and administered
online. It included a series of choice questions in which respondents chose
between two hypothetical vaccines, each characterized by four disease attributes
with varying levels describing the of risk, health impact, curability and
transmissibility of the disease they would prevent (described with four disease
attributes with varying levels of risk, health impact, curability and
transmissibility), and varying levels of four vaccine attributes (duration of
protection, number of doses required, time required for vaccination, and vaccine
cost). A random-parameters logit model was used to estimate the importance
weights each traveler type placed on the various attribute levels. These weights
were used to calculate mean monetary equivalents (MMEs) of changes in each
attribute (holding all others constant) and of hypothetical disease-vaccine
combinations. RESULTS: All traveler types' choices indicated that they attached
the greatest importance to the risk and health impact of disease and to the
vaccine cost whereas the other disease and vaccine attributes were less important
for their decisions about travel vaccines. An option of not choosing any of the
vaccine-pairs presented was rarely selected indicating that travelers' generally
prefer to be vaccinated rather than not. The MMEs of changes in vaccine
attributes indicated a very high variability between the individual travelers
within each type. CONCLUSIONS: The travelers' responses indicated strong
preferences for selecting vaccination rather than opting out of vaccination, and
disease risk, health impact and vaccine cost were the most important features for
vaccine choice.
PMID- 29338873
TI - Opioid and Psychostimulant Plasticity: Targeting Overlap in Nucleus Accumbens
Glutamate Signaling.
AB - Commonalities in addictive behavior, such as craving, stimuli-driven drug
seeking, and a high propensity for relapse following abstinence, have pushed for
a unified theory of addiction that encompasses most abused substances. This
unitary theory has recently been challenged - citing distinctions in structural
neural plasticity, biochemical signaling, and neural circuitry to argue that
addiction to opioids and psychostimulants is behaviorally and neurobiologically
distinct. Recent more selective examination of drug-induced plasticity has
highlighted that these two drug classes promote an overall reward circuitry
signaling overlap through modifying excitatory synapses in the nucleus accumbens
a key constituent of the reward system. We discuss adaptations in
presynaptic/postsynaptic and extrasynaptic glutamate signaling produced by
opioids and psychostimulants, and their relevance to circuit remodeling and
addiction-related behavior - arguing that these core neural adaptations are
important targets for developing pharmacotherapies to treat addiction to multiple
drugs.
PMID- 29338880
TI - Re: Genotype-phenotype pancreatic neuroendocrine tumor relationship in multiple
endocrine neoplasia type 1 patients: a 23-year experience at a single
institution.
PMID- 29338879
TI - Identifying lost surgical needles with visible and near infrared fluorescent
light emitting microscale coating.
AB - BACKGROUND: Retained foreign bodies (RFOs) have substantial clinical and
financial consequences. In laparoscopic surgery, RFOs can be a cause of needing
to convert a minimally invasive surgery (MIS) procedure to an open operation. A
coating for surgical models was developed to augment localization of needles
using fluorescence appropriate for open and minimally invasive surgeries
procedures. METHODS: An epoxy matrix containing both dansyl chloride and
indocyanine green was coated as visible and near infrared labels, respectively.
With ultraviolet excitation, dansyl chloride emits green fluorescence and with
NIR excitation, the ICG dye emits radiation observable with specialized near
infrared capable laparoscopes. To evaluate the coatings, open and laproscopic
surgeries were simulated in rabbits. Surgeons blinded to the type of needles
(coated or non-coated) were timed while finding needles in standard conditions
and with the use of the adjunct coatings. Control needles not located within 300
seconds were researched with the corresponding near infrared or ultraviolet
light. Localization time was evaluated for statistical significance, P < .05.
RESULTS: All dual dye coated needles searched utilizing the near infrared camera
(n = 26) or ultraviolet light (n= 26) were located within 300 seconds.
Conversely, 9 needles in both control settings (no dye usage) were not located
within 300 seconds. Mean time to locate control needles in open surgery and
laparoscopic surgery was statistically 2-3* greater than time to localization
with the use of dye as an adjunct (P = .0027 open, P < .001 laparoscopic).
CONCLUSION: Incorporation of a dual-dye fluorescent coating on surgical needles
improved the efficiency of locating needles, may minimize the need to convert
minimally invasive surgeries procedures to open, and may decrease the
consequences of a missed RFO.
PMID- 29338881
TI - Infiltration behaviour of elemental mercury DNAPL in fully and partially water
saturated porous media.
AB - Mercury is a contaminant of global concern due to its harmful effects on human
health and for the detrimental consequences of its release in the environment.
Sources of liquid elemental mercury are usually anthropogenic, such as chlor
alkali plants. To date insight into the infiltration behaviour of liquid
elemental mercury in the subsurface is lacking, although this is critical for
assessing both characterization and remediation approaches for mercury DNAPL
contaminated sites. Therefore, in this study the infiltration behaviour of
elemental mercury in fully and partially water saturated systems was investigated
using column experiments. The properties affecting the constitutive relations
governing the infiltration behaviour of liquid Hg0, and PCE for comparison, were
determined using Pc(S) experiments with different granular porous media (glass
beads and sands) for different two- and three-phase configurations. Results
showed that, in water saturated porous media, elemental mercury, as PCE, acted as
a non-wetting fluid. The required entry head for elemental mercury was higher
(from about 5 to 7 times). However, due to the almost tenfold higher density of
mercury, the required NAPL entry heads of 6.19cm and 12.51cm for mercury to
infiltrate were 37.5% to 20.7% lower than for PCE for the same porous media.
Although Leverett scaling was able to reproduce the natural tendency of Hg0 to be
more prone than PCE to infiltrate in water saturated porous media, it
considerably underestimated Hg0 infiltration capacity in comparison with the
experimental results. In the partially water saturated system, in contrast with
PCE, elemental mercury also acted as a nonwetting fluid, therefore having to
overcome an entry head to infiltrate. The required Hg0 entry heads (10.45 and
15.74cm) were considerably higher (68.9% and 25.8%) than for the water saturated
porous systems. Furthermore, in the partially water saturated systems,
experiments showed that elemental mercury displaced both air and water, depending
on the initial water distribution within the pores. This indicates that the
conventional wettability hierarchy, in which the NAPL has an intermediate wetting
state between the air and the water phases, is not valid for liquid elemental
mercury. Therefore, for future modelling of elemental mercury DNAPL infiltration
behaviour in variably water saturated porous media, a different formulation of
the governing constitutive relations will be required.
PMID- 29338882
TI - [Health model, care quality and health spending public].
PMID- 29338883
TI - Epidemiology and risk factors for chronic thromboembolic pulmonary hypertension.
PMID- 29338884
TI - Cervical Proprioception in a Young Population Who Spend Long Periods on Mobile
Devices: A 2-Group Comparative Observational Study.
AB - OBJECTIVES: The purpose of this study was to evaluate if young people with
insidious-onset neck pain who spend long periods on mobile electronic devices
(known as "text neck") have impaired cervical proprioception and if this is
related to time on devices. METHODS: A 2-group comparative observational study
was conducted at an Australian university. Twenty-two participants with text neck
and 22 asymptomatic controls, all of whom were 18 to 35 years old and spent >=4
hours per day on unsupported electronic devices, were assessed using the head
repositioning accuracy (HRA) test. Differences between groups were calculated
using independent sample t-tests, and correlations between neck pain intensity,
time on devices, and HRA test were performed using Pearson's bivariate analysis.
RESULTS: During cervical flexion, those with text neck (n = 22, mean age +/-
standard deviation [SD]: 21 +/- 4 years, 59% female) had a 3.9 degrees (SD: 1.4
degrees ) repositioning error, and the control group (n = 22, 20 +/- 1 years, 68%
female) had a 2.9 degrees (SD: 1.2 degrees ) error. The mean difference was 1
degrees (95% confidence interval: 0-2, P = .02). For other cervical movements,
there was no difference between groups. There was a moderately significant
correlation (P <= .05) between time spent on electronic devices and cervical pain
intensity and between cervical pain intensity and HRA during flexion. CONCLUSION:
The participants with text neck had a greater proprioceptive error during
cervical flexion compared with controls. This could be related to neck pain and
time spent on electronic devices.
PMID- 29338885
TI - Concurrence of rheumatoid arthritis and calcium pyrophosphate deposition disease:
A case collection and review of the literature.
AB - OBJECTIVE: Calcium pyrophosphate deposition disease (CPDD) is arthritis caused by
calcium pyrophosphate (CPP) crystal deposition in joints. It is commonly
associated with aging as well as a handful of metabolic syndromes. Recent
epidemiologic studies suggest a positive association of CPDD and rheumatoid
arthritis (RA). Yet how these diseases are related remains unclear. We set out to
describe 21 well-characterized patients with both diagnoses. METHODS: Medical
records of patients with both RA and CPDD identified at a single academic
practice site were reviewed for age, gender, age of CPDD and RA onset, disease
duration, joint involvement, and lab values including rheumatoid factor (RF),
cyclic citrullinated peptide antibody (CCP), iron studies, and parathyroid
hormone and calcium levels. RESULTS: The mean age of CPDD onset was 69.5 +/- 11.4
years, with a mean RA age onset of 53.9 +/- 16 years, demonstrating a mean lag of
13.4 +/- 10.9 years between diagnoses. The majority of RA patients were diagnosed
with CPDD based on the presence of radiographic chondrocalcinosis (15/21). The
most commonly involved joint was the knee, followed by the wrist, hip, and
shoulder. CONCLUSIONS: These data show that the diagnosis of RA often precedes
the diagnosis of CPDD. This asynchronous presentation taken together with the
classic age of onset for CPDD and typical pattern of joint involvement supports
the hypothesis that CPDD develops in RA patients through similar processes as
those that cause the idiopathic forms of this disease.
PMID- 29338886
TI - Overweight and obesity status in pregnant women are related to intestinal
microbiota and serum metabolic and inflammatory profiles.
AB - BACKGROUND: Overweight and obesity may predispose women to clinical complications
during their pregnancy. We hypothesize that a higher degree of overweight status
is related to a range of aberrations in biomarkers already in early pregnancy.
Our objective was to investigate whether intestinal microbiota, serum metabolic
and inflammatory profiles differ in relation to the degree of overweight status
in pregnant women. METHODS: This study investigated 52 overweight and 47 obese
pregnant women in early pregnancy. Fecal samples were analyzed for intestinal
microbiota composition by 16S ribosomal RNA gene sequencing and Qiime pipeline.
Circulating serum metabolites, including lipids, amino acids and GlycA, a marker
of low-grade inflammation, were analyzed by NMR metabolomics and hsCRP was
quantified by immunoassay. Serum zonulin levels were analyzed to depict
intestinal permeability by Zonulin ELISA kit and LPS activity for endotoxemia by
Limulus amebocyte lysate assay. The analyses were adjusted for multiple
comparisons using Benjamini-Hochberg procedure for false discovery rate
controlling. RESULTS: The relative abundance of bacterial family Prevotellaceae
(adjusted P = 0.19) and markers of low-grade inflammation, hsCRP (P = 0.0015) and
GlycA (P < 0.001) and three branched chain amino acids (isoleucine, adjusted P =
0.024; leucine, adjusted P = 0.026; valine, adjusted P = 0.10) and one aromatic
amino acid (phenylalanine, adjusted P = 0.050) and concentrations of several VLDL
particles and lipid measures in several VLDL particles were higher in obese
pregnant women compared to their overweight pregnant counterparts (adjusted P <
0.12). In contrast, lipid measures in a few HDL particles and many fatty acids
were lower in obese compared to overweight pregnant women (adjusted P < 0.12).
CONCLUSIONS: The detected alterations in intestinal microbiota and metabolic and
inflammatory profiles related to obesity status may offer new alternative tools
to supplement standard clinical measures to predict the risk for metabolic
alterations during the early phase of pregnancy.
PMID- 29338887
TI - Reply to Crivelli et al.: The different faces of fear and threat. Evolutionary
and cultural insights.
PMID- 29338888
TI - Vibrio communities in scleractinian corals differ according to health status and
geographic location in the Mediterranean Sea.
AB - The increase in seawater temperature associated with global warming is a
significant threat to coral health and is linked to increasing mass mortality
events and Vibrio-related coral diseases. In the Mediterranean Sea, the endemic
Cladocora caespitosa and the invasive species Oculina patagonica are the main
scleractinian corals affected by mass mortalities. In this study, culturable
Vibrio spp. assemblages associated with healthy and unhealthy colonies of these
two shallow coral species were characterized to assess the presence of Vibrio
pathogens in tissue necrosis. Vibrio communities associated with O. patagonica
and C. caespitosa showed geographical differences, although these became more
homogeneous in unhealthy specimens of both species. Furthermore, the number of
recovered Vibrio specimens was more than five times higher in unhealthy than in
healthy corals. Within these culturable vibrios, the known pathogens Vibrio
mediterranei and Vibrio coralliilyticus were present in unhealthy colonies of
both coral species in the two localities, suggesting that they could play a role
in the health status of C. caespitosa and thus act as generalist pathogens in
Mediterranean corals. Nonetheless, a clonal type of V. coralliilyticus detected
in C. caespitosa was not associated with disease signs, suggesting that this
species could encompass assemblages with different levels of virulence.
PMID- 29338890
TI - Corrigendum on "Isorhamnetin augments the anti-tumor effect of capeciatbine
through the negative regulation of NF-kappaB signaling cascade in gastric cancer"
[Cancer Lett. 363 (1) (2015) 28-36].
PMID- 29338889
TI - Situational HIV stigma and stimulant use: A day-level autoregressive cross-lagged
path model among HIV-positive gay and bisexual men.
AB - BACKGROUND: Data on the association between HIV stigma and drug use are scarce,
but some research suggests that internalized HIV stigma may be associated with
increased drug use and that this association may be at least partially mediated
by emotion dysregulation. We sought to test this hypothesis with event-level data
to more accurately tease out the co-occurrence of these phenomena. METHODS: We
conducted a 21-day, twice-daily ecological momentary assessment study with a
sample of 52 HIV-positive gay and bisexual men. We utilized multivariate
multilevel path analysis to test an autoregressive cross-lagged model of the
direct and indirect effects of situational-level internalized HIV stigma and
emotion dysregulation on non-prescription stimulant drug use. RESULTS: As
hypothesized, we observed significant concurrent effects of internalized HIV
stigma on emotion dysregulation as well as autoregressive associations of
internalized HIV stigma and emotion dysregulation with themselves across the day.
Furthermore, findings revealed direct effects of internalized HIV stigma on later
emotion dysregulation and increased likelihood of stimulant use, but no direct
effect of emotion dysregulation on stimulant use. CONCLUSIONS: Situational
increases in internalized HIV stigma appear to exert a direct risk-enhancing
effect on the likelihood of daily stimulant drug use and do not appear to do so
through emotion dysregulation. Future research is needed to more carefully
examine distinct affective experiences and regulation strategies to better
understand what mechanism links internalized HIV stigma with drug use behaviors.
PMID- 29338891
TI - Gray and white matter changes and their relation to illness trajectory in first
episode psychosis.
AB - Previous works have studied structural brain characteristics in first-episode
psychosis (FEP), but few have focused on the relation between brain differences
and illness trajectories. The aim of this study is to analyze gray and white
matter changes in FEP patients and their relation with one-year clinical
outcomes. A sample of 41 FEP patients and 41 healthy controls (HC), matched by
age and educational level was scanned with a 3T MRI during the first month of
illness onset. One year later, patients were assigned to two illness trajectories
(schizophrenia and non-schizophrenia). Voxel-based morphometry (VBM) was used for
gray matter and Tract-based spatial statistics (TBSS) was used for white matter
data analysis. VBM revealed significant and widespread bilateral gray matter
density differences between FEP and HC groups in areas that included the right
insular Cortex, the inferior frontal gyrus and orbito-frontal cortices, and
segments of the occipital cortex. TBSS showed a significant lower fractional
anisotropy (FA) in 8 clusters that included segments of the anterior thalamic
radiation, the left body and forceps minor of corpus callosum, the right anterior
segment of the inferior fronto-occipital fasciculus and the anterior segments of
the cingulum. The sub-groups comparison revealed significant lower FA in the
schizophrenia sub-group in two clusters: the anterior thalamic radiation and the
anterior segment of left cingulum. These findings are coherent with previous
morphology studies. The results suggest that gray and white matter abnormalities
are present at early stages of the disease, and white matter differences may
distinguish different illness prognosis.
PMID- 29338892
TI - Treatment of intraoral ranulas with a two-incision fistula technique: the
management of recurrence.
AB - The two-incision fistula technique for the treatment of oral ranulas has recently
been introduced to clinical practice. We reviewed 52 patients who had recurrences
after this treatment, and explored the possible causes and underlying mechanisms.
A total of 13/53 ranulas had recurred, so we repeated the operation, and one
patient had the ranula and the sublingual gland resected. We found that the thin
mucous membrane cracked at the double incisions, which led to the formation of a
fistula and promoted the drainage of cystic fluid. The results indicated that the
recurrence of ranulas after the two-incision fistula technique can be reduced
further. To avoid recurrence, the technique should be adjusted slightly,
depending on the type of ranula present.
PMID- 29338893
TI - The Desired Role of Health Care Providers in Guiding Older Patients With Distal
Radius Fractures: A Qualitative Analysis.
AB - PURPOSE: Understanding patient preferences for shared decision making is valuable
for surgeons to advance patient-centered care, particularly in cases where there
is not a clearly superior treatment option, like distal radius fracture. The
existing evidence presents conflicting views on the desired role of the provider
among older patients when making medical decisions. We aimed to investigate the
perceived versus desired role of the provider in older adult patients with distal
radius fracture. METHODS: Thirty patients (>=62 years old) who had sustained a
distal radius fracture within the past 5 years were recruited from the screening
process of the Wrist and Radius Injury Surgical Trial at the principal
investigator's site using purposive sampling. A trained member of the research
team conducted interviews in a semistructured format with the help of an
interview guide. Findings were derived following the principles of grounded
theory. RESULTS: Participants experienced varied levels of shared decision making
with the hand surgeon. Subjects' perceived role of the surgeon did not always
match their desired role. Most patients placed distinct trust in the
recommendations of hand specialists regarding the technical aspects of the
treatment. Nonetheless, respondents wanted to provide input when decisions
pertained to outcomes or functionality. Many patients sought outside support from
family or friends in the health care field, regardless of the outside source's
medical specialty. CONCLUSIONS: Despite conflicting evidence, most older adult
patients desire a shared approach when making treatment decisions. Exchanging
information and preferences on outcomes of each treatment option may be more
important to the patient than detailing the specific technical aspects of their
care. CLINICAL RELEVANCE: To provide high quality care, surgeons should evaluate
the desired role of the patient to make treatment decisions at the start of their
interaction. Surgeons must be aware of outside medical influences that guide
their patients' decision-making processes.
PMID- 29338894
TI - LGBT Populations' Barriers to Cancer Care.
AB - OBJECTIVE: To describe lesbian, gay, bisexual, and transgender (LGBT)
individuals' barriers to accessing and receiving quality cancer care. DATA
SOURCES: Published data on cancer care and studies of LGBT individuals.
CONCLUSION: There is a clustering of barriers among LGBT individuals, which
suggests multiple inequities exist in LGBT individuals' cancer care, although
data on disparities along the cancer control continuum are not consistently
available. IMPLICATIONS FOR NURSING PRACTICE: Nurses can make a difference in
LGBT individuals' cancer care by obtaining training on LGBT health and their
cancer-related needs and by providing a welcoming and respectful relationship
with LGBT patients.
PMID- 29338895
TI - Feasibility of total intravenous anesthesia by cardiologists with the support of
anesthesiologists during catheter ablation of atrial fibrillation.
AB - BACKGROUND: The optimal methodology for sedation and anesthesia during atrial
fibrillation (AF) ablation has not been well established. We assessed the
feasibility of total intravenous anesthesia (TIVA) by cardiologists with support
from anesthesiologists during AF ablation and quality of pulmonary vein isolation
(PVI) and single procedure success rate at 12 months. METHODS: TIVA was performed
by cardiologists using IV propofol and fentanyl under controlled ventilation via
i-gelTM without neuromuscular blocking drugs in 160 consecutive patients (80
nonparoxysmal) with no anticipated difficult airway or other severe diseases.
Anesthesiologists were requested to be on standby during the procedure. The
incidence of anesthesia-associated complications and ablation-associated
complications were assessed. To evaluate the quality of PVI, the prevalence of
acute adenosine triphosphate (ATP)-provoked PV reconnections and late PV
reconnections among those requiring a redo procedure was analyzed. RESULTS: TIVA
was successfully completed in 152 patients (95%). In five (3%), we requested help
from anesthesiologists, and in three (2%), TIVA was abandoned. No major
anesthesia-associated complications were observed. Ablation-associated
complications were observed in seven patients (4%). ATP provocation test was
performed in 141 patients, and no acute PV reconnections were observed in 134
(95%). Success rates at 12 months were 85% of patients off antiarrhythmic drugs.
Twenty-one of 24 patients with recurrence underwent a redo session, and 18 (86%)
had no PV reconnections. CONCLUSIONS: TIVA by cardiologists with support from
anesthesiologists during AF ablation may be feasible. The success rate at 12
months was high, and prevalence of acute and late PV reconnection was very low.
PMID- 29338896
TI - Novel bioabsorbable polymer and polymer-free metallic drug-eluting stents.
AB - The introduction of drug-eluting stents (DES) significantly reduced angiographic
restenosis and the clinical need for revascularization following percutaneous
coronary intervention. However, concerns remain regarding the long-term safety
and efficacy of DES. The use of durable polymers for drug elution that have
limited biocompatibility is thought to contribute toward DES failure, by
promoting an adverse local inflammatory response and vascular toxicity.
Biodegradable polymer and polymer-free metallic stents represent two novel
technological solutions to this challenging clinical problem. This review
summarizes the available clinical evidence supporting the use of either
biodegradable polymer or polymer-free DES platforms.
PMID- 29338898
TI - Acute Respiratory Failure Due to Chronic Tophaceous Gout With Laryngeal and
Bronchial Involvement: An Unusual Complication.
PMID- 29338897
TI - Asymptomatic bacteriuria and urinary tract infection in pregnant women with and
without diabetes: Cohort study.
AB - OBJECTIVE: To compare the prevalence of asymptomatic bacteriuria (ASB) and the
incidence of urinary tract infection (UTI) in pregnant women with and without
diabetes mellitus (DM) or gestational DM (GDM). STUDY DESIGN: We performed a
cohort study in five hospitals and two midwifery clinics in the Netherlands.
Pregnant women with and without DM or GDM were screened for the presence of ASB
around 12 and 32 weeks' gestation. Characteristics of participants as well as
outcome data were collected from questionnaires and medical records. ASB was
defined as the growth of at least 10e5 cfu/ml isolated from the urine of a woman
without UTI complaints. UTI was considered to be present when a treating
physician had diagnosed UTI and prescribed antibiotics. RESULTS: We studied 202
women with and 272 women without DM or GDM. Of all women 31.7% with and 94.9%
without DM or GDM provided a week 12 sample. The prevalence of ASB was comparable
in women with and without DM or GDM (12 weeks' n = 322; 4.7% and 2.3%; relative
risk (RR) 2.02; 95% confidence interval (CI) 0.52-7.84; 32 weeks' n = 422; 3.2%
and 3.0%; RR 1.06; 95% CI 0.36-3.09), as was the incidence of UTI (16.8% and
12.9%; RR 1.31; 95% CI 0.85-2.02). Neither ASB nor UTI were associated with
preterm birth or babies being small for gestational age. CONCLUSION: In pregnant
women with and women without DM or GDM, the overall prevalence of ASB was low.
Neither ASB nor UTI did differ significantly between the groups. Our data
discourage a routine ASB screen and treat policy in pregnant women with DM or
GDM.
PMID- 29338899
TI - Hyponatremia in COPD: a Little Known Complication.
PMID- 29338900
TI - Noninvasive ventilation failure in pneumonia patients >=65years old: The role of
cough strength.
PMID- 29338901
TI - High degree heart block following suicide attempt by hanging.
PMID- 29338902
TI - Stage-specific expression of DDX4 and c-kit at different developmental stages of
the porcine testis.
AB - Spermatogenesis begins with spermatogonial stem cells (SSCs), which are located
in the basement membrane of the adult testes. Previous studies have described
specific biomarkers for undifferentiated porcine spermatogonia or SSCs; however,
these markers are not sufficient to understand spermatogenesis at different
developmental stages. The objective of this study was characterize the expression
of DEAD-Box polypeptide 4 (DDX4, also known as VASA) and tyrosine-protein kinase
kit (c-kit), as potential markers of male germ cells in the porcine testis. In
porcine testis tissue at prepubertal stages (5, 30, and 60 days), DDX4 and c-kit
protein expression was detected in the most undifferentiated spermatogonia, which
also express protein gene product 9.5 (PGP9.5). However, in porcine testis
tissues from pubertal and postpubertal stages (90, 120, and 150 days), DDX4 and c
kit were not detected in PGP9.5-positive undifferentiated spermatogonia. The DDX4
expression pattern was similar to that of c-kit in the porcine testis. In adult
porcine testes, DDX4-expressing cells were located on the lumenal side, compared
to synaptonemal complex protein 3-positive primary spermatocytes, but DDX-4 was
not co-expressed with acrosin, a known acrosome marker. In addition, DDX4 was
detected in PGP9.5-expressing porcine SSCs in culture. Based on our results, we
suggest that DDX4 and c-kit are putative markers of undifferentiated
spermatogonia in the prepubertal porcine testis. While in the postpubertal
porcine testis, they are markers of differentiated spermatocytes. These findings
may facilitate future studies of porcine spermatogenesis.
PMID- 29338903
TI - Clinical workflow optimization to improve 4DCT reconstruction for Toshiba
Aquilion CT scanners.
AB - Respiratory motion remains a source of major uncertainties in radiotherapy.
Respiratory correlated computed tomography (referred to as 4DCT) serves as one
way of reducing breathing artifacts in 3D-CTs and allows the investigation of
tumor motion over time. The quality of the 4DCT images depends on the data
acquisition scheme, which in turn is dependent on the vendor. Specifically, the
only way Toshiba Aquilion LB CT scanners can reconstruct 4DCTs is a cycle-based
reconstruction using triggers provided by an external surrogate signal. The
accuracy is strongly dependent on the method of trigger generation. Two
consecutive triggers are used to define a breathing cycle which is divided into
respiratory phases of equal duration. The goal of this study is to identify if
there are advantages in the usage of local-amplitude based sorting (LAS) of the
respiration motion states, in order to reduce image artifacts and improve 4DCT
quality. Furthermore, this study addresses the generation and optimization of a
clinical workflow using as surrogate motion monitoring system the SentinelTM (C
RAD AB, Sweden) optical surface scanner in combination with a Toshiba Aquilion LB
CT scanner. For that purpose, a phantom study using 10 different breathing
waveforms and a retrospective patient study using the 4DCT reconstructions of 10
different patients has been conducted. The error in tumor volume has been reduced
from 2.9+/-3.7% to 2.7+/-2.6% using optimal cycle-based triggers (manipulated
CBS) and to 2.7+/-2.2% using LAS in the phantom study. Moreover, it was possible
to decrease the tumor volume variability from 5.0+/-3.6% using the original cycle
based triggers (original CBS) to 3.5+/-2.5% using the optimal triggers and to
3.7+/-2.7% using LAS in the patient data analysis. We therefore propose the usage
of the manipulated CBS, also with regard to an accurate and safe clinical
workflow.
PMID- 29338904
TI - Pain and its Impact on the Functional Ability in Children Treated at the
Children's Cancer Center of Lebanon.
AB - PURPOSE: The purpose of this study was to describe the characteristics of pain in
children under treatment at the Children Cancer Centre of Lebanon at the American
University of Beirut Medical Centre. Design and Methods A cross-sectional
correlational survey was used. The Adolescent Pediatric Pain Tool and the
Functional Disability Inventory were used to examine the characteristics of pain
experienced in a consecutive sample of children treated at the CCCL and its
impact on their functional abilities. RESULTS: The mean age of the 62
participants was 12.3 (SD 2.9). The overall mean pain intensity rating for the
sample was 5.06 (SD 1.87) on a 10 cm Word Graphic Rating Scale. More than one
half of the children in the sample (57.4%) reported having pain "sometimes" with
a median duration of two hours per pain episode. The most frequently reported
locations of pain were the forehead, the abdomen, and the lower back. For the
most part, the children used sensory words to describe their pain experience. The
children reported moderate levels of functional disability (mean FDI score 25.04,
SD 13.81). Multivariable linear regression analysis identified frequency,
duration, location, use of affective descriptors, and treatments as statistically
significant predictors of pain intensity. CONCLUSION: Regrettably, the findings
reported attest once again to unrelieved pain in a pediatric oncology population.
PRACTICE IMPLICATIONS: Policy makers can contribute to pain control by
introducing legislation and national policies to ensure adequate pain management
for children with cancer in Lebanon.
PMID- 29338905
TI - Posterior Reversible Encephalopathy Syndrome: A Rare Childhood Case with
Unconsciousness.
AB - BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a condition
characterized by seizures, altered consciousness, visual disturbances, and
headache. Characteristic findings on neuroimaging include cerebral edema,
typically involving the parieto-occipital white matter. PRES has been associated
with hypertension, autoimmune disease, and Henoch-Scholein purpura (HSP), but few
cases have been reported, and fewer cases of PRES have been reported in children.
CASE REPORT: We report the case of a 4-year-old girl who presented with blindness
and semi-consciousness. The patient had no significant medical history and no
abnormalities on physical examination or laboratory testing, although she had
slightly elevated blood pressure. After hospitalization, the patient showed some
characteristic signs of HSP and cranial magnetic resonance imaging revealed PRES
as the cause of semi-consciousness. In our discussion, we examine the clinical
features of PRES and remarkable points for the clinical diagnosis and management
of this rare but important disease. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF
THIS?: Although reports of PRES in children are rare, PRES should be considered
in the differential diagnosis of children presenting with disturbance of
consciousness. Emergency physicians should consult with pediatric physicians to
confirm diagnoses of PRES and determine an appropriate treatment plan, given its
variable etiology. Measurements of blood pressure, which are often missing in
pediatric cases, can help physicians to arrive at a correct diagnosis.
PMID- 29338906
TI - Virtual computed tomography morphometry of the patella for estimation of sex
using postmortem Japanese adult data in forensic identification.
AB - In forensic anthropological identification of human remains and single bones,
computed tomography (CT) data analysis facilitates volumetric and radiographic
density analyses, and a recently developed automated analysis system markedly
improved the performance, accuracy, and reproducibility of three-dimensional (3
D) reconstruction. The present study aimed to investigate virtual CT morphometry
of the patella for the estimation of sex using postmortem CT data of forensic
autopsy cases of Japanese individuals aged >=18 years (total n=220; 110 males and
110 females; estimated postmortem interval <88h), especially with regard to the
efficacy of 3-D bone volumetry. Sex-related differences were detected for all
parameters (males>females; p<0.0001), but the differences were the most notable
for bone mass volume; the estimated cut-off values (cm3) for discriminating males
and females were 20.35 with a sensitivity and specificity of 0.85 and 0.91 for
the left side and 19.96 with a sensitivity and specificity of 0.83 and 0.92 for
the right side, respectively. The mean CT value showed an age-dependent decrease
and was particularly low in females aged >60years. These findings indicate the
efficacy of virtual CT morphometry of the patella using an automated analyzer for
sex estimation.
PMID- 29338907
TI - New photodynamic molecular beacons (PMB) as potential cancer-targeted agents in
PDT.
AB - Further improvements in Photodynamic therapy (PDT) necessitate that the dye
targets more selectively tumour tissues or neovascularization than healthy cells.
Different enzymes such as matrix metalloproteinases (MMPs) are overexpressed in
tumour areas. Among these MMPs, gelatinases (MMP-2 and MMP-9) and its activator
MMP-14 are known to play a key role in tumour angiogenesis and the growth of many
cancers such as glioblastoma multiforme (GBM), an aggressive malignant tumour of
the brain. These last years, the concept of photodynamic molecular beacons (PMB)
became interesting for controlling the photosensitizer's ability to generate
singlet oxygen (1O2) close to target biomolecules as MMPs. We report herein novel
PMBs triggered by MMP-2 and/or MMP-9 and/or MMP-14, comprising a photosensitizer
and a singlet oxygen quencher linked by MMP cleavable peptide linker (H
GRIGFLRTAKGG-OH). First of all, we focused on the synthesis and the photophysical
study of different derivatives photosensitizer-peptide. This preliminary work
concluded on an influence of the nature and the distance from the peptide, but
not of the position of the photosensitizer in these derivatives on the
proteolytic enzymatic action. The nature of the quencher used (a blackberry
quencher (BBQ-650) or a black hole quencher (BHQ3)) does not influence the
enzymatic action. We also studied the influence of an additional PEG spacer.
Finally, the synthesis, the singlet oxygen quenching efficiency and the enzymatic
activation of these new MMP- cleavable-PMBs were compared.
PMID- 29338908
TI - Relationship between neuropathy proximal to the suprascapular nerve and rotator
cuff tear in a rodent model.
AB - BACKGROUND: Rotator cuff tears are believed to coexist with cervical spine
lesions. In cases of preexisting neuropathy, such as cervical spine lesions,
fatty degeneration has likely already occurred due to the neuropathy. In these
cases, rotator cuff tear is thought to occur easily because of preexisting
extensive fatty degeneration and degeneration of the tendons due to neuropathy.
This study aimed to evaluate the effects of paralysis due to neuropathy proximal
to the suprascapular nerve on the supraspinatus and infraspinatus tendons using a
rat model of brachial plexus paralysis. METHODS: This study included fifteen, 8
week-old Sprague-Dawley rats. The left shoulder was included in the paralysis
group and the contralateral shoulder constituted the sham group. Biomechanical
testing (evaluated maximum tear force, maximum displacement and Young's modulus)
(n = 10) and histological analyses (n = 5) (using the Bonar scale) were performed
at 12 weeks postoperatively to confirm the degeneration of the tendon. RESULTS:
The mean maximum tear force was significantly lower in the paralysis group than
in the sham group (P = 0.008), indicating that rotator cuff tears occurred with a
lower force in the paralysis group. Additionally, the average Young's modulus was
significantly greater in the paralysis group than in the sham group (P = 0.003),
indicating that the rotator cuff muscle became hard and inflexible in the
paralysis group. The Bonar scales of the histological analyses were significantly
higher in the paralysis group (total score = 7.04 +/- 0.61) than the sham group
(total score = 0) (p < 0.0001). CONCLUSIONS: If neuropathy of proximal to the
suprascapular nerve, such as cervical spine or brachial plexus lesion, exists,
weakness and degeneration of the rotator cuff tendon and stiffness of the rotator
cuff muscle develop. Neuropathy is likely a cause of rotator cuff tears.
PMID- 29338909
TI - Essential structure of orexin 1 receptor antagonist YNT-707, Part II: Drastic
effect of the 14-hydroxy group on the orexin 1 receptor antagonistic activity.
AB - The 14-dehydration- and 14-H derivatives of the orexin 1 receptor (OX1R)
antagonist YNT-707 (2) were synthesized. The obtained derivatives showed higher
affinities for OX1R than the corresponding 14-hydroxy derivatives. The
conformational analysis suggested that the 17-sulfonamide groups in the
derivatives without the 14-hydroxy group have a greater tendency to be oriented
toward the upper side of the D-ring compared with the 14-hydroxy derivatives.
Additionally, the 14-dehydration-derivative with 6alpha-amide side chain showed
significantly higher affinity than the 14-hydroxy derivative, while the
corresponding 14-H derivative showed only slightly higher affinity. Thus, the 14
hydroxy group strongly affects the affinity of the antagonist for the OX1R.
PMID- 29338910
TI - Synthesis of deuterium-labelled analogues of NLRP3 inflammasome inhibitor MCC950.
AB - This study describes the syntheses of di, tetra and hexa deuterated analogues of
the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome
inhibitor MCC950. In di and tetra deuterated analogues, deuteriums were
incorporated into the 1,2,3,5,6,7-hexahydro-s-indacene moiety, whereas in the
hexa deuterated MCC950 deuteriums were incorporated into the 2-(furan-3-yl)propan
2-ol moiety. The di deuterated MCC950 analogue was synthesised from 4-amino
3,5,6,7-tetrahydro-s-indacen-1(2H)-one 5. Tetra deuterated analogues were
synthesised in 10 chemical steps starting with 5-bromo-2,3-dihydro-1H-inden-1-one
9, whereas the hexa deuterated analogue was synthesised in four chemical steps
starting with ethyl-3-furoate 24. All of the compounds exhibited similar activity
to MCC950 (IC50 = 8 nM). These deuterated analogues are useful as internal
standards in LC-MS analyses of biological samples from in vivo studies.
PMID- 29338911
TI - Rosette-forming glioneuronal tumor of the fourth ventricle. Two cases report and
literature review.
AB - Rosette-forming glioneuronal tumor of the fourth ventricle is a primary central
nervous system tumor introduced in the group of glioneuronal tumors in the WHO
classification of 2007. Initially it was described around the fourth ventricle,
but recently have been published cases in different locations. We present 2cases
of this rare tumor, both surgically treated. The first in a 41 year old man with
typical symptoms of posterior fossa injury. The second in an 18 year old woman,
with incidental finding of posterior fossa injury that was also surgically
treated. We present pre- and post-surgical magnetic resonance images,
histological pictures of this tumor and we make a review of the literature.
PMID- 29338912
TI - Surgical outcomes of traumatic cervical fractures in patients with ankylosing
spondylitis.
AB - OBJECTIVE: Ankylosing spondylitis is an inflammatory rheumatic disease mainly
affecting the axial skeleton. The rigid spine may secondarily develop
osteoporosis, further increasing the risk of spinal fracture. In this study, we
reviewed fractures in patients with ankylosing spondylitis that had been
clinically diagnosed to better define the mechanism of injury, associated
neurological deficit, predisposing factors, and management strategies. METHODS:
Between January 2004 and December 2014, 6 patients with ankylosing spondylitis
and neurological complications after injuries were treated. Neuroimaging
evaluation was obtained in all patients by using plain radiography, CT scan, and
MR imaging. The ASIA Impairment Scale was used in order to evaluate the
neurologic status of the patients. Surgical decision was based on relationship of
neurological involvement and spinal instability. RESULTS: A total of 6 cervical
injuries were identified in a review of patients in whom ankylosing spondylitis
had been diagnosed. Of these, 2 patients were associated with a hyperextension
mechanism and 4 cases by flexion mechanism. Posttraumatic neurological deficits
were demonstrated in all 6 cases and neurological improvement after surgery was
observed in 4 of these cases. The two cases were not improved by the surgery was
on a case by presenting a degree of Asia A and another patient who initially
improved with surgery but died of pneumonia in the postoperative. CONCLUSIONS:
Patients with ankylosing spondylitis are highly susceptible to spinal fracture
and spinal cord injury even after only mild trauma. Initial CT or MR imaging of
the whole spine is recommended even if the patient's symptoms are mild. The
patient should also have early surgical stabilization to correct spinal deformity
and avoid worsening of the patient's neurological status.
PMID- 29338913
TI - Discrepancies in staging, treatment, and delays to treatment may explain
disparities in bladder cancer outcomes: An update from the National Cancer Data
Base (2004-2013).
AB - INTRODUCTION: We sought to characterize national disparities in the diagnosis of
advanced stage bladder cancer. Among patients with advanced disease, we explored
disparities in overall survival, treatment, and time to treatment. METHODS AND
MATERIALS: We queried the National Cancer Data Base for patients diagnosed with
bladder urothelial carcinoma. We used multivariable logistic regression to assess
the association between covariates and diagnosis of advanced disease (AJCC stage
III-IV). We used Kaplan-Meier, log-rank, and Cox proportional analyses to
evaluate disparities in overall survival for patients with advanced disease.
Receipt of treatment and delays to treatment were compared between subgroups.
RESULTS: Among our cohort of 328,560 patients, 7.6% were diagnosed with advanced
disease. Female sex, black race, Hispanic ethnicity, and living in a region of
lower income and education were all associated with increased odds of advanced
disease. Female sex (HR = 1.16; 95% CI: 1.12-1.20; P<0.001), black race (HR =
1.10; 95% CI: 1.04-1.18; P = 0.002), and lower regional income levels (fourth
quartile compared to first: HR = 1.08; 95% CI: 1.02-1.16; P = 0.016) portended
worse overall survival. Chemotherapy (HR = 0.55, 95% CI: 0.53-0.57; P<0.001) and
radical cystectomy (HR = 0.61; 95% CI: 0.59-0.64, P<0.001) improved survival.
Females, black patients, and patients from regions of lower income and education
were less likely to receive treatment and less likely to receive treatment within
12 weeks of diagnosis. CONCLUSION: There are several disparities in the diagnosis
and treatment of advanced bladder cancer. Overall survival for certain groups may
benefit from earlier diagnosis and improved timely access to potentially life
prolonging treatment.
PMID- 29338914
TI - Prophylactic antibiotics following radical cystectomy reduces urinary tract
infections and readmission for sepsis from a urinary source.
AB - INTRODUCTION: Urinary tract infections (UTI) and sepsis contribute significantly
to the morbidity associated with cystectomy and urinary diversion in the first 30
days. We hypothesized that continuous antibiotic prophylaxis decreased UTIs in
the first 30 days following radical cystectomy. METHODS: Patients with urothelial
carcinoma of the bladder who underwent a radical cystectomy with urinary
diversion for bladder cancer at Oregon Health and Science University from January
2014 to May 2015 were included in the study. The ureteral stents were kept for 3
weeks in both groups. In October 2014, we enacted a Department Quality Initiative
to reduce UTIs. Following the initiative, all radical cystectomy patients were
discharged home on antibiotic prophylaxis following a postoperative urine culture
obtained during hospitalization. To evaluate the effectiveness of the initiative,
the last 42 patients before the initiative were compared to the first 42 patients
after the initiative with regard to the rate of UTI in the first 30 days
following surgery. We used a combination of comprehensive chart review and the
American College of Surgeons' National Surgical Quality Improvement Program
(NSQIP) to determine UTI and readmission for urosepsis in the first 30 days
following surgery. This ensured accurate capture of all patients developing a
UTI. RESULTS: A total of 12% in the prophylactic antibiotic group had a
documented UTI, whereas 36% in the no antibiotic group had a urinary tract
infection (P<0.004). A total of 1 (2%) patient in the antibiotic group was
readmitted for urosepsis whereas 7 (17%) patients in the no antibiotic group were
admitted for urosepsis (P = 0.02). There was no association noted between urine
culture at discharge and the development of UTI in the 30-day postdischarge
period (P = 0.75). The median time to UTI was 19 days and the most common
organism was Enterococcus (32%). Thirty-percent of patients not receiving
prophylaxis developed a UTI 1 day after ureteral stent removal. No patients had a
UTI following stent removal in the prophylaxis group. No adverse antibiotic
related events were noted. CONCLUSION: Prophylactic antibiotics in the 30 days
following radical cystectomy is associated with a significant decrease in urinary
tract infections and readmission from urosepsis after surgery.
PMID- 29338915
TI - The significance of avoiding household food waste - A means-end-chain approach.
AB - Many humans suffer from hunger, while edible food is discarded. This study aims
at showing the importance of avoiding food waste in households and its causes by
applying the means-end-chain analysis. Additional the means-end-chain approach
should be examined in how far the method is suitable to get insights towards this
topic. Consumer backgrounds in terms of feelings and attitudes regarding food
waste should be shown, with the particular question why food waste personally is
important. The data collection occurred utilizing the hard laddering method
within a quantitative online survey. The results indicate that avoiding food
waste is important for the greater part of consumers, as many claim to have a bad
conscience, seeing it as morally wrong and reprehensible to waste food. A sample
breakdown of gender, age and income points differences among these groups in
regards to psychological consequences and value systems. Financial and
environmental aspects have a lesser impact on attitudes and feelings regarding
food waste in households.
PMID- 29338916
TI - Patent foramen ovale closure vs. medical therapy for recurrent stroke prevention:
Evolution of treatment effect during follow-up.
AB - BACKGROUND: Little is known regarding changes in treatment effect over time
associated with patent foramen ovale (PFO) closure among patients with embolic
stroke of unknown origin. METHODS: We reconstructed Kaplan-Meier curves for
stroke from individual randomized trials comparing PFO closure vs. medical
therapy among patients with embolic stroke. Random effects Cox-regression
analyses were performed in order to estimate hazard ratios (HRs) with 95%
confidence intervals (95%CIs). RESULTS: A total of 2531 patients enrolled across
4 randomized trials were included. PFO closure was associated with a significant
reduction in the risk of stroke at longest available follow-up (HR 0.18, 95%CI
0.06 to 0.59, P=0.005). However, recurrent stroke was already significantly
reduced among patients randomized to PFO closure at 1-year (HR 0.40, 95%CI 0.20
to 0.80, P=0.010), with the treatment effect remaining consistent (P-for
interaction=0.356) between 1- and 5-year (HR 0.14, 95%CI 0.05 to 0.55, P=0.005)
and beyond 5-year (HR 0.20, 95%CI 0.03 to 1.19, P=0.077). CONCLUSIONS: Among
patients with embolic stroke of unknown origin, PFO closure reduces the risk of
stroke compared with medical therapy, with a significant reduction in recurrences
starting already within 1-year after percutaneous PFO closure.
PMID- 29338917
TI - Exercise training in adults with repaired tetralogy of Fallot: A randomized
controlled pilot study of continuous versus interval training.
AB - INTRODUCTION: Adults with repaired tetralogy of Fallot (ToF) have impaired
exercise capacity, vascular and cardiac autonomic function, and quality of life
(QoL). Specific effects of high-intensity interval or moderate continuous
exercise training on these parameters in adults with repaired ToF remain unknown.
METHODS AND RESULTS: Thirty adults with repaired ToF were randomized to either
high-intensity interval, moderate intensity continuous training (36 sessions, 2-3
times a week) or usual care (no supervised exercise). Exercise capacity, flow
mediated vasodilation, pulse wave velocity, NT-proBNP and fibrinogen levels,
heart rate variability and recovery, and QoL (SF-36 questionnaire) were
determined at baseline and after the intervention period. Twenty-seven patients
(mean age 39+/-9years, 63% females, 9 from each group) completed this pilot
study. Both training groups improved in at least some parameters of
cardiovascular health compared to no exercise. Interval-but not continuous
training improved VO2peak (21.2 to 22.9ml/kg/min, p=0.004), flow-mediated
vasodilation (8.4 to 12.9%, p=0.019), pulse wave velocity (5.4 to 4.8m/s,
p=0.028), NT-proBNP (202 to 190ng/L, p=0.032) and fibrinogen levels (2.67 to
2.46g/L, p=0.018). Conversely, continuous-but not interval-training improved
heart rate variability (low-frequency domain, 0.32 to 0.22, p=0.039), heart rate
recovery after 2min post-exercise (40 to 47 beats, p=0.023) and mental domain of
SF-36 (87 to 95, p=0.028). CONCLUSION: Both interval and continuous exercise
training modalities were safe. Interval training seems more efficacious in
improving exercise capacity, vascular function, NT-proBNP and fibrinogen levels,
while continuous training seems more efficacious in improving cardiac autonomic
function and QoL. (Clinicaltrials.gov, NCT02643810).
PMID- 29338918
TI - Filling pressures in Fontan revisited: Comparison between pulmonary artery wedge,
ventricular end-diastolic, and left atrial pressures in adults.
AB - BACKGROUND: Pulmonary artery wedge pressure (PAWP) has been shown to correlate
better with left atrial pressure (LAP) than ventricular end-diastolic pressure
(VEDP) in acquired heart disease. The correlation between VEDP and PAWP and their
performance as surrogates for LAP in Fontan patients is unknown. METHODS: Offline
single-beat simultaneous measurement of PAWP and VEDP was performed in 50 adult
Fontan patients and non-simultaneous hemodynamic data abstracted for calculation
of pulmonary vascular resistance (PVR). For the evaluation of PAWP and VEDP as
surrogates for LAP, 14 fenestrated adult Fontan patients were included. RESULTS:
Mean age was 34.2+/-10years and 54% of patients were female. Tricuspid atresia
and double inlet left ventricle were the most common congenital defects (44% and
20%, respectively). Simultaneous mean VEDP was 10.8+/-4.6mmHg and mean PAWP was
11+/-4.6mmHg; the PAWP-VEDP correlation was 0.91 (p<0.001). Using non
simultaneous data, right-sided (mean difference 0.6WU.m2, 95% CI 0.2-1.0;
p=0.005) and left-sided (mean difference 0.5WU.m2, 95% CI 0.1-0.9; p=0.02) PVRs
were significantly higher when PAWP rather than VEDP was used. In fenestrated
patients, LAP-right PAWP and LAP-left PAWP correlations were 0.97 and 0.95
(p<0.0001 for both), respectively, whereas the correlation between LAP-VEDP was
0.76 (p=0.007). CONCLUSIONS: PAWP and VEDP correlate reasonably well in adult
Fontan patients but PAWP is a better surrogate for LAP. The use of VEDP instead
of PAWP appears to significantly underestimate PVR in these patients.
PMID- 29338919
TI - Agreement among Magnetic Resonance Imaging/Magnetic Resonance
Cholangiopancreatography (MRI-MRCP) and Endoscopic Ultrasound (EUS) in the
evaluation of morphological features of Branch Duct Intraductal Papillary
Mucinous Neoplasm (BD-IPMN).
AB - BACKGROUND/OBJECTIVES: To evaluate the agreement between the imaging modalities
MRI-MRCP and EUS in cystic lesions of the pancreas which were thought to be a BD
IPMN. METHODS: Multicenter retrospective study included all patients between 2010
and 2015 with a suspected BD-IPMN who underwent an EUS and MRI-MRCP within 6
months or less of each other. Location, number, size, worrisome features and high
risk stigmata were evaluated. Interobserver agreement was evaluated by Kappa
score. RESULTS: 173 patients were included (97 UHSC, 76 UCLH-RFH), mean age 65
(range 25-87 years), 66 males. When comparing both modalities there was good
agreement for the location of the cyst. The median lesion size was larger by MRI
MRCP than EUS although it was not significant. With regards to worrisome
features, there was moderate agreement for main PD of 5-9 mm and abrupt change (k
= 0.45 and 0.52). Fair agreement was seen for the cyst wall thickening (k =
0.25). No agreement was seen between the presence of non-enhanced mural nodules
or lymphadenopathy (k < 0). With regards to high-risk stigmata, poor agreement
was obtained for the detection of an enhanced solid component (k = 0.12). No
agreement was observed for main PD > 10 mm (k < 0). CONCLUSIONS: In this
multicentre study of patients with a BD-IPMN under active surveillance, most
disagreement between these modalities was seen in the proximal pancreas. There
was generally only minimal concordance between the imaging findings of EUS and
MRI-MRCP for the detection of high-risk stigmata and worrisome features.
PMID- 29338920
TI - Endoscopic ultrasound guided 22 gauge core needle biopsy for the diagnosis of
Autoimmune pancreatitis.
AB - BACKGROUND: It is difficult to obtain adequate tissue sample for diagnosing
autoimmune pancreatitis (AIP) with the help of traditional EUS-guided FNA. As per
ICDC guidelines, EUS-guided FNA is not recommended for diagnosing AIP(1). We
herein present a report of 2 cases of using a new flexible 22 gauge (G) core
biopsy needle (SharkCore, Medtronic, Sunnydale, Calif) for diagnosing AIP.
METHODS: This is a report of 2 cases reviewed retrospectively which had used 22G
core biopsy needle for obtaining histo-pathological samples for diagnosing AIP.
The cases were reviewed with both endoscopist and a pathologist to determine if
the diagnostic criteria were met. RESULTS: Both the cases had adequate tissue
sample obtained to make a clear diagnosis of AIP. Pathology showed changes of
chronic pancreatitis with atrophy and storiform pattern of fibrosis with a dense
lymphoplasmacytic infiltrate in both cases along with identification of IgG4
cells. CONCLUSION: EUS-guided fine needle biopsy (FNB) using the SharkCore needle
can be used reliably for diagnosing AIP. More studies need to be performed to
validate this further.
PMID- 29338921
TI - Faster progression from MCI to probable AD for carriers of a single-nucleotide
polymorphism associated with type 2 diabetes.
AB - Sporadic Alzheimer's disease (AD), as opposed to its autosomal dominant form, is
likely caused by a complex interaction of genetic, environmental, and health
lifestyle factors. Twin studies indicate that sporadic AD heritability could be
between 58% and 79%, around half of which is explained by the epsilon4 allele of
the apolipoprotein E (APOE4). We hypothesized that genes associated with known
risk factors for AD, namely hypertension, hypercholesterolemia, obesity,
diabetes, and cardiovascular disease, would contribute significantly to the
remaining heritability. We analyzed 22 AD-associated single-nucleotide
polymorphisms (SNPs), associated with these risk factors, that were included in
the sequencing data of the Alzheimer's Disease Neuroimaging Initiative 1 data
set, which included 355 participants with mild cognitive impairment (MCI). We
built survival models with the selected SNPs to predict progression of MCI to
probable AD over the 10-year follow-up of the study. The rs391300 SNP, located on
the serine racemase (SRR) gene and linked to increased susceptibility to type 2
diabetes, was associated with progression from MCI to probable AD.
PMID- 29338922
TI - Alcohol consumption, masculinity, and alcohol-related violence and anti-social
behaviour in sportspeople.
AB - OBJECTIVES: There is no research examining alcohol-related aggression and anti
social behaviour in UK or European sportspeople (athletes), and no research has
examined relationships between masculinity, alcohol consumption, and alcohol
related aggression and antisocial behaviour in sportspeople (athletes). This
study addresses this gap. DESIGN: Cross-sectional. METHODS: A sample (N=2048;
women=892, 44%) of in season sportspeople enrolled at UK universities (response
83%), completed measures of masculinity, alcohol consumption, within-sport (on
field) violence, and having been the perpetrator and/or victim of alcohol-related
violent/aggressive and antisocial behaviour (e.g., hit/assaulted, vandalism,
sexual assault). Logistic regressions examined predictors of alcohol-related
violence/aggression and anti-social behaviours. RESULTS: Significant bivariate
relationships between masculinity, within-sport violence, alcohol consumption,
and alcohol-related aggression and anti-social behaviour were found for both men
and women (p's<.001). Logistic regression adjusting for all variables showed that
higher levels of masculinity and alcohol consumption in men and women were
related to an increased odds of having conducted an aggressive, violent and/or
anti-social act in the past 12 months when intoxicated. Odds ratios were largest
for relationships between masculinity, alcohol consumption, within-sport
violence, and interpersonal violence/aggression (p's<.001). A similar pattern of
results was found for having been the victim of aggression and anti-social
behaviour. CONCLUSIONS: Alcohol-related aggression and anti-social behaviour
appear to be problematic in UK university sportspeople, and is related to
masculinity and excessive drinking. Interventions that reduce excessive alcohol
consumption, masculine norms and associated within-sport violence, could be
effective in reducing alcohol-related aggression and antisocial behaviour in UK
sportspeople.
PMID- 29338924
TI - Dynamic Epigenetic Changes during Plant Regeneration.
AB - Plants have the remarkable ability to drive cellular dedifferentiation and
regeneration. Changes in epigenetic landscapes accompany the cell fate
transition. Notably, modifications of chromatin structure occur primarily during
callus formation via an in vitro tissue culture process and, thus, pluripotent
callus cells have unique epigenetic signatures. Here, we highlight the latest
progress in epigenetic regulation of callus formation in plants, which addresses
fundamental questions related to cell fate changes and pluripotency
establishment. Global and local modifications of chromatin structure underlie
callus formation, and the combination and sequence of epigenetic modifications
further shape intricate cell fate changes. This review illustrates how a series
of chromatin marks change dynamically during callus formation and their
biological relevance in plant regeneration.
PMID- 29338923
TI - Minimally invasive hysterectomy surgery rates for endometrial cancer performed at
National Comprehensive Cancer Network (NCCN) Centers.
AB - OBJECTIVES: Minimally invasive surgery (MIS) is a quality measure for endometrial
cancer (EC) established by the Society of Gynecologic Oncology and the American
College of Surgeons. Our study objective was to assess the proportion of EC cases
performed by MIS at National Comprehensive Cancer Network (NCCN) centers and
evaluate perioperative outcomes. METHODS: A retrospective cohort study of women
who underwent surgical treatment for EC from 2013 to 2014 was conducted at four
NCCN centers. Multivariable mixed logistic regression models analyzed factors
associated with failure to perform MIS and perioperative complications. RESULTS:
In total 1621 patients were evaluated; 86.5% underwent MIS (robotic-assisted
72.5%, laparoscopic 20.9%, vaginal 6.6%). On multivariable analysis, factors
associated with failure to undergo MIS were uterine size >12cm (Odds Ratio [OR]:
0.17, 95% CI 0.03-0.9), stage III (OR: 0.16, 95% CI 0.05-0.49) and IV disease
(OR: 0.07, 95% CI 0.02-0.22). For stage I/II disease, complications occurred in
5.1% of MIS and 21.7% of laparotomy cases (p<0.01). Laparotomy was associated
with increases in any complication (OR: 6.0, 95% CI 3.3-10.8), gastrointestinal
(OR: 7.2, 95% CI 2.6-19.5), wound (OR: 3.7, 95% CI 1.5-9.2), respiratory (OR
37.5, 95% CI 3.9-358.0), VTE (OR 10.5, 95% CI 1.3-82.8) and 30-day readmission
(OR: 2.6, 95% CI 1.4-4.9) compared to MIS. CONCLUSIONS: At NCCN-designated
centers, the MIS hysterectomy rate in EC is higher than the published national
average, with low perioperative complications. Previously identified disparities
of age, race, and BMI were not observed. A proposed MIS hysterectomy benchmark of
>80% in EC care is feasible when performed at high volume centers.
PMID- 29338925
TI - Rituximab therapy in rheumatoid arthritis and primary biliary cholangitis.
PMID- 29338926
TI - Can you tell the difference: Round vs anatomical implants - A real-time global
ballot.
PMID- 29338927
TI - Brain injury due to head banging in Tourette.
PMID- 29338928
TI - Immunoproteomic identification of antigenic candidate Campylobacter jejuni and
human peripheral nerve proteins involved in Guillain-Barre syndrome.
AB - Immunoproteomics is become a potent methodology used for identifying
immunoreactive proteins. In this study, an immunoproteomic approach based on 2
dimensional gel electrophoresis (2D-PAGE) and immunoblotting combined with high
resolution mass spectrometry (MS) was used to identify immunoreactive proteins
that might be involved in mechanisms of Guillain-Barre syndrome (GBS)
development, regardless of their potential reciprocal molecular mimicry. Proteins
isolated from C. jejuni and human peripheral nerve tissue (HPN) were separated
with 2D SDS-PAGE and subjected to western blotting using serum samples from GBS
patients. The peptides generated after proteolysis of the immunoreactive proteins
were submitted to nanoflow-high performance liquid chromatography-nano
electrospray ionization coupled to high resolution mass spectrometry (nHPLC-nESI
MS and MS/MS) followed by SEQUESTdata analysis for proteins identification. In C.
jejuni, immunoreactivity was found for GroEL and DnaK, structural proteins
(MOMP), key enzymatic proteins necessary for the microbial proliferation
(adenylate kinase, enolase, inorganic pyrophosphatase and aspartate ammonia
lyase), and antioxidant enzymes (alkyl hydroperoxide reductase-AhpC and DNA
protection during starvation protein - DNA protection factor against Fe2+
mediated oxidative stress). HPN immunoreactive proteins identified were heat
shock proteins (HSP), intermediate filaments (vimentin and desmin), and other
proteins and enzymes such as troponin/tropomyosin complex and ATP synthase
subunit beta and the keratan sulfate proteoglycan lumican. The targeting of
vimentin and desmin, suggested that the neuronal autoimmune damage is
specifically directed to intermediate neuronal (vimentin) and neuromuscular IF,
probably localized nearby cell surface, affording increased accessibility to
autoantibodies. These findings suggest that the post-infectious development of
GBS may be also associated to additional concomitant immune factors that lead to
nerve damage generated by auto-immune trigger(s) different from molecular
mimicry.
PMID- 29338929
TI - Differential anxiety-like behavior, HPA responsiveness, and host-resistance in
mice with different circling preference.
AB - Relationships between behavioral sidedness and immune responses in previous
studies have differed depending on behavior tests and severity of biological
stress in mice. It was necessary to elucidate the psychophysiological mediators
that connect behavioral sidedness and immune responses. This study investigated
interrelationships among anxiety-like behavior, the HPA axis responsiveness, and
host-resistance to bacterial infection. Mice that preferred clockwise circling
had lower locomotor activities, higher anxiety-like behavior, and faster
activation of the HPA axis than mice that preferred counterclockwise circling. A
fast activation of the HPA axis was associated with a higher host-resistance to
low dose bacterial infection.
PMID- 29338930
TI - Neurologic disorders associated with anti-glutamic acid decarboxylase antibodies:
A comparison of anti-GAD antibody titers and time-dependent changes between
neurologic disease and type I diabetes mellitus.
AB - To determine clinical features of neurologic disorders associated with anti
glutamic acid decarboxylase antibodies (anti-GAD-Ab), we examined titers and time
dependent changes of anti-GAD-Ab. Six patients, stiff person syndrome (2),
cerebellar ataxia (1), limbic encephalitis (1), epilepsy (1), brainstem
encephalitis (1), were compared with 87 type I diabetes mellitus (T1DM) patients
without neurologic disorders. Anti-GAD-Ab titers and index were higher in
neurologic disorders than in T1DM, suggesting intrathecal antibody synthesis.
Anti-GAD-Ab titers in T1DM decreased over time, whereas they remained high in
neurologic disorders. Immunotherapy improved neurological disorders and anti-GAD
Ab titers and index provide clinically meaningful information about their
diagnostic accuracy.
PMID- 29338932
TI - Functional characteristics of a renal H+/lipophilic cation antiport system in
porcine LLC-PK1 cells and rats.
AB - We have recently found an H+/quinidine (a lipophilic cation, QND) antiport system
in Madin-Darby canine kidney (MDCK) cells. The primary aim of the present study
was to evaluate whether the H+/lipophilic cation antiport system is expressed in
porcine LLC-PK1 cells. That is, we investigated uptake and/or efflux of QND and
another cation, bisoprolol, in LLC-PK1 cells. In addition, we studied the renal
clearance of bisoprolol in rats. Uptake of QND into LLC-PK1 cells was decreased
by acidification of the extracellular pH or alkalization of the intracellular pH.
Cellular uptake of QND from the apical side was much greater than from the
basolateral side. In addition, apical efflux of QND from LLC-PK1 cells was
increased by acidification of the extracellular pH. Furthermore, lipophilic
cationic drugs significantly reduced uptake of bisoprolol in LLC-PK1 cells. Renal
clearance of bisoprolol in rats was approximately 7-fold higher than that of
creatinine, and was markedly decreased by alkalization of the urine pH. The
present study suggests that the H+/lipophilic cation antiport system is expressed
in the apical membrane of LLC-PK1 cells. Moreover, the H+/lipophilic cation
antiport system may be responsible for renal tubular secretion of bisoprolol in
rats.
PMID- 29338931
TI - In vitro activity of eravacycline against 2213 Gram-negative and 2424 Gram
positive bacterial pathogens isolated in Canadian hospital laboratories: CANWARD
surveillance study 2014-2015.
AB - Gram-negative (n=2213) and Gram-positive (n=2424) pathogens isolated from
patients in 13 Canadian hospitals in 2014 and 2015 were tested for in vitro
susceptibility to eravacycline and comparators using the Clinical and Laboratory
Standards Institute broth microdilution method. The concentration of eravacycline
inhibiting 90% of isolates (MIC90) ranged from 0.5 to 2MUg/mL for 9 species of
Enterobacteriaceae tested (n=2067). Eravacycline activity was largely unaffected
by extended-spectrum beta-lactamase phenotypes in Escherichia coli (n=141) and
Klebsiella pneumoniae (n=21). Eravacycline was active against Acinetobacter
baumannii (n=28; MIC90, 0.5MUg/mL) and Stenotrophomonas maltophilia (n=118;
MIC90, 4MUg/mL). Eravacycline MIC90 for staphylococci (n=1653), enterococci
(n=289), and streptococci (n=482) ranged from 0.12 to 0.25, 0.06 to 0.12, and
0.015 to 0.06MUg/mL, respectively. Eravacycline's potency was equivalent to or 2-
to 4-fold greater than tigecycline against Enterobacteriaceae and Gram-positive
cocci tested. Eravacycline demonstrates promising activity against recent
clinical Gram-negative and Gram-positive bacteria, including multidrug-resistant
pathogens.
PMID- 29338933
TI - Physiological based pharmacokinetic modeling to estimate in vivo Ki of
ketoconazole on renal P-gp using human drug-drug interaction study result of
fesoterodine and ketoconazole.
AB - This study was conducted to estimate in vivo inhibition constant (Ki) of
ketoconazole on renal P-glycoprotein (P-gp) using human drug-drug interaction
(DDI) study result of fesoterodine and ketoconazole. Fesoterodine is a prodrug
which is extensively hydrolyzed by non-specific esterases to the active
metabolite 5-hydroxymethyl tolterodine (5-HMT). 5-HMT is then further metabolized
via Cytochrome P450 (CYP) 2D6 and CYP3A4. It is reported that 5-HMT is a
substrate of P-gp whereas fesoterodine is not. Renal clearance of 5-HMT is
approximately two-times greater than renal glomerular filtration rate. This
suggests the possibility that renal clearance of 5-HMT involves secretion by P
gp. Utilizing the available pharmacokinetic characteristics of fesoterodine and 5
HMT, we estimated in vivo Ki of ketoconazole on P-gp at kidney based on DDI study
data using physiologically-based pharmacokinetic approach. The estimated in vivo
Ki of ketoconazole for hepatic CYP3A4 (6.64 ng/mL) was consistent with the
reported values. The in vivo Ki of ketoconazole for renal P-gp was successfully
estimated as 2.27 ng/mL, which was notably lower than reported in vitro 50%
inhibitory concentration (IC50) values ranged 223-2440 ng/mL due to different
condition between in vitro and in vivo.
PMID- 29338934
TI - Systematic review of the safety and effectiveness of peripheral neurostimulation
of the sphenopalatine ganglion for the treatment of refractory chronic cluster
headache.
AB - INTRODUCTION: This study aimed to assess the safety and effectiveness of
peripheral neurostimulation of the sphenopalatine ganglion (SPG) in the treatment
of refractory chronic cluster headache. DEVELOPMENT: Various medical databases
were used to perform a systematic review of the scientific literature. The search
for articles continued until 31 October 2016, and included clinical trials,
systematic reviews and/or meta-analyses, health technology assessment reports,
and clinical practice guidelines that included measurements of
efficiency/effectiveness or adverse effects associated with the treatment. The
review excluded cohort studies, case-control studies, case series, literature
reviews, letters to the editor, opinion pieces, editorials, and studies that had
been duplicated or outdated by later publications from the same institution.
Regarding effectiveness, we found that SPG stimulation had positive results for
pain relief, attack frequency, medication use, and patients' quality of life. In
the results regarding safety, we found a significant number of adverse events in
the first 30 days following the intervention. Removal of the device was necessary
in some patients. Little follow-up data, and no long-term data, is available.
CONCLUSIONS: These results are promising, despite the limited evidence available.
We consider it essential for research to continue into the safety and efficacy of
SPG stimulation for patients with refractory chronic cluster headache. In cases
where this intervention may be indicated, treatment should be closely monitored.
PMID- 29338935
TI - Compassionate use of human recombinant insulin-like growth factor-1 therapy in
Friedreich's ataxia.
PMID- 29338936
TI - Continuous intestinal infusion of levodopa-carbidopa in patients with advanced
Parkinson's disease in Spain: Subanalysis by autonomous community.
AB - OBJECTIVES: To compare the characteristics of patients undergoing treatment with
continuous intestinal infusion of levodopa-carbidopa (CIILC) for advanced
Parkinson's disease and the data on the effectiveness and safety of CIILC in the
different autonomous communities (AC) of Spain. METHODS: A retrospective,
longitudinal, observational study was carried out into 177 patients from 11 CAs
who underwent CIILC between January 2006 and December 2011. We analysed data on
patients' clinical and demographic characteristics, variables related to
effectiveness (changes in off time/on time with or without disabling dyskinesia;
changes in Hoehn and Yahr scale and Unified Parkinson's Disease Rating Scale
scores; non-motor symptoms; and Clinical Global Impression scale scores) and
safety (adverse events), and the rate of CIILC discontinuation. RESULTS:
Significant differences were observed between CAs for several baseline variables:
duration of disease progression prior to CIILC onset, off time (34.9-59.7%) and
on time (2.6-48.0%; with or without disabling dyskinesia), Hoehn and Yahr score
during on time, Unified Parkinson's Disease Rating Scale-III score during both on
and off time, presence of>= 4 motor symptoms, and CIILC dose. Significant
differences were observed during follow-up (> 24 months in 9 of the 11 CAs
studied) for the percentage of off time and on time without disabling dyskinesia,
adverse events frequency, and Clinical Global Impression scores. The rate of
CIILC discontinuation was between 20-40% in 9 CAs (78 and 80% in remaining 2
CAs). CONCLUSIONS: This study reveals a marked variability between CAs in terms
of patient selection and CIILC safety and effectiveness. These results may have
been influenced by patients' baseline characteristics, the availability of
multidisciplinary teams, and clinical experience.
PMID- 29338937
TI - Neuroimaging in hypoglycaemic encephalopathy diagnosis and prognosis: A case
report.
PMID- 29338938
TI - Distinct MET Protein Localization Associated With MET Exon 14 Mutation Types in
Patients With Non-small-cell Lung Cancer.
AB - BACKGROUND: The MET gene has been recognized as a potential important therapeutic
target in non-small-cell lung cancer (NSCLC). We sought to investigate the MET
exon 14 mutations in a cohort of Chinese patients with NSCLC. METHODS: We tested
461 NSCLCs for MET exon 14 mutations by sequencing whole exon 14 and its flanking
introns. The protein expression was determined by immunohistochemical analysis.
RESULTS: In this study, we identified MET exon 14 mutations in 9 (2.0%) of 461
NSCLCs. Of these 9 mutations, 7 (77.8%) were located in the splice sites of MET
exon 14, with MET overexpression in 6. One point mutation c.3010C>T
(p.Arg1004Ter) was nonsense mutation with no MET expression. One insertion
mutation was within exon 14 of MET with MET overexpression. MET protein
localization in tumor cells with MET exon 14 mutations was different between
mutation types. Three point mutations that disrupted the splice donor site of
intron 14 were membranous staining, whereas the other mutations were cytoplasmic
staining. Patients with MET exon 14 splice site mutations were significantly
older. The incidence of MET exon 14 mutations in sarcomatoid carcinoma was
significantly higher than in other histologic types (P = .034). CONCLUSION:
Distinct MET protein localization is associated with MET exon 14 mutation types
in patients with NSCLC. Different MET exon 14 mutation types were identified in a
subset of Chinese patients with NSCLC who could possibly benefit from MET
targeted therapy.
PMID- 29338939
TI - Immune Cytokines and Their Receptors in Inflammatory Pain.
AB - There is burgeoning interest in the interaction between the immune and nervous
systems. Pain is mediated by primary sensory neurons (nociceptors) that can
respond to a variety of thermal, mechanical and chemical signals. Cytokines are
now recognized as important mediators of inflammatory pain. They can induce
nociceptor sensitization indirectly via mediators, wherein neurons become primed
and thus become more responsive to stimulation; alternatively, there is also
evidence that cytokines can directly activate neurons via their specific
receptors present on the neuronal cells. We review here the evidence for and
against these respective mechanisms, focusing on arthritis and inflammatory skin
models. A number of striking inconsistencies amongst the conclusions made in the
literature are highlighted and discussed.
PMID- 29338940
TI - Chimney Stent Technique in a Valve-in-valve Procedure.
PMID- 29338941
TI - Epiglottoplasty technique in endoscopic partial laryngectomy.
AB - The main advantage of endoscopic laser surgery for laryngeal cancer is to allow
tumour resection, while limiting functional sequelae, thereby improving the
postoperative course. In this type of surgery, the epiglottis is often partially
resected, leaving a raw zone without any reconstruction. The surgical technique
described here involves endoscopic reconstruction of the epiglottis after partial
resection. The sectioned edge of the epiglottis is sutured to the base of the
tongue to create a neoepiglottis and to reconstruct the vallecula, thus
resembling preoperative anatomy, allowing improvement of postoperative
swallowing.
PMID- 29338942
TI - International consensus (ICON) on treatment of Meniere's disease.
AB - OBJECTIVE: To present the international consensus for recommendations for
Meniere's disease (MD) treatment. METHODS: Based on a literature review and
report of 4 experts from 4 continents, the recommendations have been presented
during the 21st IFOS congress in Paris, in June 2017 and are presented in this
work. RESULTS: The recommendation is to change the lifestyle, to use the
vestibular rehabilitation in the intercritic period and to propose psychotherapy.
As a conservative medical treatment of first line, the authors recommend to use
diuretics and Betahistine or local pressure therapy. When medical treatment
fails, the recommendation is to use a second line treatment, which consists in
the intratympanic injection of steroids. Then as a third line treatment,
depending on the hearing function, could be either the endolymphatic sac surgery
(when hearing is worth being preserved) or the intratympanic injection of
gentamicin (with higher risks of hearing loss). The very last option is the
destructive surgical treatment labyrinthectomy, associated or not to cochlear
implantation or vestibular nerve section (when hearing is worth being preserved),
which is the most frequent option.
PMID- 29338943
TI - Physiology of the paransal sinus ostia: Endoscopic findings.
PMID- 29338944
TI - Histological and morphofunctional parameters of the hypothalamic-pituitary
adrenal system are sensitive to daidzein treatment in the adult rat.
AB - The isoflavone, daidzein is a biologically active, plant-derived compound that
interacts with estrogen receptors. Data from previous studies have suggested that
daidzein exerts beneficial effects in many diseases; however, as an endocrine
disrupter, it may also alter the functioning of the endocrine system. Data
regarding the effect of daidzein on the morphofunctional and histological
parameters of the hypothalamic-pituitary-adrenal (HPA) system is still lacking.
Therefore, using the newCAST stereological software, we investigated the effects
of chronic (21 days) daidzein treatment on corticotropin-releasing hormone (CRH)
neurons within the hypothalamus and corticotropes (ACTH cells) in the pituitary,
while image analysis was employed to-examine the intensity of fluorescence of CRH
in the median eminence (ME) and adrenocorticotropin hormone in the pituitary in
adult orchidectomized (Ovx) rats. Circulating ACTH and corticosterone levels were
also analyzed. This study showed that daidzein treatment decreased the volume
density of CRH neurons within the paraventricular nucleus as well as CRH
immunofluorescence in the ME. The total number of ACTH cells was decreased, while
ACTH cell volume and the intensity of ACTH fluorescence were increased following
daidzein treatment. Both ACTH and corticosterone blood levels were increased
after daidzein administration. The results of performed experiments clearly
demonstrate that volume density of CRH neurons; total number and volume of ACTH
cells, as well as stress hormones levels are vulnerable to the effects of
daidzein.
PMID- 29338945
TI - Editorial Comment.
PMID- 29338946
TI - Reply.
PMID- 29338947
TI - Reply.
PMID- 29338948
TI - Editorial Comment.
PMID- 29338949
TI - Relation between cadmium exposure and gestational diabetes mellitus.
AB - BACKGROUND: Cadmium (Cd) has been associated with type 2 diabetes in general
population. However, the role of Cd in the occurrence of Gestational diabetes
mellitus (GDM) remains unclear. OBJECTIVES: Our study was aimed at investigating
whether Cd exposure during pregnancy was associated with increased risk of GDM.
METHODS: Cd concentrations were measured in urine samples from 6837 pregnant
women in Wuhan, China, from 2012 to 2014. A "modified Poisson" model with a
robust error variance was used to examine the association of GDM with continuous
natural logarithm (ln) transformed urinary Cd or quartiles of urinary Cd levels.
RESULTS: For about 3-fold increase in Cd concentrations, there were 16% [relative
risk (RR) =1.16; 95% confidence interval (CI): 1.03, 1.33] increase in risk of
GDM. Compared with women in the lowest quartile of urinary Cd levels, women in
the highest quartile had 1.30 higher risk of GDM [95% CI: 1.05, 1.61; p-trend
<0.05]. Further analyses indicated overweight/obese women with higher urinary Cd
levels had significantly higher risk of GDM, compared with women in the reference
category of lowest quartile of Cd and normal pre-pregnancy body mass index [RR
=2.71; 95% CI: 1.81, 4.07]. CONCLUSIONS: Our study presented a significantly
positive association between urinary Cd levels and risk of GDM, supporting the
hypothesis that environmental exposure to Cd may contribute to the development of
GDM.
PMID- 29338950
TI - Sugar-Sweetened Beverage and Water Intake in Relation to Diet Quality in U.S.
Children.
AB - INTRODUCTION: Sugar-sweetened beverages (SSBs) are a major contributor to
children's added sugar consumption. This study examines whether children's SSB
and water intakes are associated with diet quality and total energy intake.
METHODS: Using data on children aged 2-18 years from the 2009-2014 National
Health and Nutrition Examination Survey, linear regression models were used to
analyze SSB and water intake in relation to Healthy Eating Index 2010 (HEI-2010)
scores and total energy intake. Generalized linear models were used to analyze
SSB and water intake in relation to the HEI-2010 scores. Analyses were conducted
including and excluding caloric contributions from SSBs and were conducted in
2016-2017. RESULTS: SSB intake was inversely associated with the HEI-2010 total
scores (9.5-point lower score comparing more than two servings/day with zero
servings/day, p-trend<0.0001) and positively associated with total energy intake
(394 kcal higher comparing more than two servings/day with zero servings/day, p
trend<0.0001). The associations between SSB and HEI-2010 total scores were
similar when SSBs were excluded from HEI-2010 calculations. Water intake was
positively associated with HEI-2010 total scores, but not associated with total
energy intake. SSB intake was inversely associated with several HEI-2010
component scores, notably vegetables, total fruit, whole fruit, greens and beans,
whole grains, dairy, seafood and plant proteins, and empty calories. Water intake
was positively associated with most of the same HEI-2010 component scores.
CONCLUSIONS: Children who consume SSBs have poorer diet quality and higher total
energy intake than children who do not consume SSBs. Interventions for obesity
and chronic disease should focus on replacing SSBs with water and improving other
aspects of diet quality that correlate with SSB consumption.
PMID- 29338951
TI - Small Incentives Improve Weight Loss in Women From Disadvantaged Backgrounds.
AB - INTRODUCTION: Women from lower-income backgrounds have the highest rates of
obesity. Thus, effective programs for this high-risk population are urgently
needed. Evidence suggests that adding financial incentives to treatment helps to
engage and promote health behavior change in lower-income populations; however,
this has never been tested in women for obesity treatment. The purpose of this
study was to examine whether adding small financial incentives to Internet weight
loss treatment yields better weight loss outcomes in women from lower-income
backgrounds compared with the same treatment without incentives. Weight losses in
lower-versus higher-income women were also compared. METHODS: Data were pooled
from two randomized trials in which women (N=264) received either Internet
behavioral weight loss treatment (IBWL) or IBWL plus incentives (IBWL+$). Weight
was objectively assessed. Data were collected and analyzed from 2011 to 2017.
RESULTS: Women from lower-income backgrounds had significantly better weight loss
outcomes in IBWL+$ compared with IBWL alone (6.4 [SD=4.9%] vs 2.6 [SD=4.6%],
p=0.01). Moreover, a greater percentage achieved a >=5% weight loss in IBWL+$ vs
IBWL alone (52.6% vs 38.1%, p=0.01). Interestingly, the comparison between lower
income versus higher-income groups showed that, in IBWL alone, women with lower
income achieved significantly poorer weight losses (3.4 [SD=4.2%] vs 4.9
[SD=4.0%], p=0.03). By contrast, in IBWL+$, weight loss outcomes did not differ
by income status (5.0 [SD=5.6%] vs 5.3 [SD=3.8%], p=0.80), and a similar
percentage of lower- versus higher-income women achieved a >=5% weight loss
(52.6% vs 53.8%, p=0.93). CONCLUSIONS: An Internet behavioral weight loss program
plus financial incentives may be an effective strategy to promote excellent
weight losses in women with lower income, thereby enhancing equity in treatment
outcomes in a vulnerable, high-risk population. These data also provide important
evidence to support federally funded incentive initiatives for lower-income,
underserved populations.
PMID- 29338952
TI - Behavioral Risk Factors and Regional Variation in Cardiovascular Health Care and
Death.
AB - INTRODUCTION: Reducing the burden of death from cardiovascular disease includes
risk factor reduction and medical interventions. METHODS: This was an
observational analysis at the hospital service area (HSA) level, to examine
regional variation and relationships between behavioral risks, health services
utilization, and cardiovascular disease mortality (the outcome of interest). HSA
level prevalence of cardiovascular disease behavioral risks (smoking, poor diet,
physical inactivity) were calculated from the Behavioral Risk Factor Surveillance
System; HSA-level rates of stress tests, diagnostic cardiac catheterization, and
revascularization from a statewide multi-payer claims data set from Maine in 2013
(with 606,260 patients aged >=35 years), and deaths from state death certificate
data. Analyses were done in 2016. RESULTS: There were marked differences across
32 Maine HSAs in behavioral risks: smoking (12.4%-28.6%); poor diet (43.6%
73.0%); and physical inactivity (16.4%-37.9%). After adjustment for behavioral
risks, rates of utilization varied by HSA: stress tests (28.2-62.4 per 1,000
person-years, coefficient of variation=17.5); diagnostic cardiac catheterization
(10.0-19.8 per 1,000 person-years, coefficient of variation=17.3); and
revascularization (4.6-6.2 per 1,000 person-years; coefficient of variation=9.1).
Strong HSA-level associations between behavioral risk factors and cardiovascular
disease mortality were observed: smoking (R2=0.52); poor diet (R2=0.38); and
physical inactivity (R2=0.35), and no association between revascularization and
cardiovascular disease mortality after adjustment for behavioral risk factors
(R2=0.02). HSA-level behavioral risk factors were also strongly associated with
all-cause mortality: smoking (R2=0.57); poor diet (R2=0.49); and physical
inactivity (R2=0.46). CONCLUSIONS: There is substantial regional variation in
behavioral risks and cardiac utilization. Behavioral risk factors are associated
with cardiovascular disease mortality regionally, whereas revascularization is
not. Efforts to reduce cardiovascular disease mortality in populations should
focus on prevention efforts targeting modifiable risk factors.
PMID- 29338953
TI - Violent Crime and Park Use in Low-Income Urban Neighborhoods.
AB - INTRODUCTION: Crime and safety are often cited as potential hurdles to park use
and park-based physical activity. Using comprehensive data sources including both
objective and subjective measurements at the park level and the individual level,
this study aimed to assess the association between crime rates and use of local
parks in low-income urban neighborhoods. METHODS: The authors observed 48 parks
and conducted local resident surveys in low-income neighborhoods in Los Angeles
during a 2-year study period (2013-2015). Crime data were geocoded within a 1
mile radius of parks' addresses and longitudinal models were fitted to estimate
the association between crime rates and park use outcomes in 2017. RESULTS: One
gun-related violent crime per 10,000 people during the 6-month period prior to
data collection was associated with an average of 13.5%-15.8% reduction in
observed park use and park-based moderate to vigorous physical activity (p<0.05)
in the 6-month observation period. The relationship was significant in seniors
(33%-40% reduction) and adults (13%-18%), but insignificant for teenagers (2%-4%)
and children (10%-12%). Homicide rates were also significantly related to lower
self-reported park use (p<0.05). CONCLUSIONS: Gun-related violent crimes have
relatively long-term negative associations with population health by reducing
utilization of outdoor park space. There can be additional population health
benefits from controlling and reducing gun-related violent crimes beyond
immediate impacts on public safety and mortality.
PMID- 29338954
TI - Perceived and Observed Food Environments, Eating Behaviors, and BMI.
AB - INTRODUCTION: This study examines relationships between perceived and observed
nutrition environments, diet, and BMI, in order to examine the criterion validity
of the Nutrition Environment Measures Survey-Perceived (NEMS-P). METHODS: In a
cross-sectional study, perceived nutrition environments were assessed (NEMS-P)
among 221 adults from four neighborhoods in the Philadelphia area in 2010 and
2011. A total of 158 food store environments were observed using the NEMS-Stores.
Data analyses were conducted in 2016. Bivariate Spearman rank correlations were
used to examine relationships between perceived and observed availability,
quality, and price of fruits and vegetables in respondents' neighborhoods. Linear
regression models were used to examine relationships between perceived
neighborhood and home food environments and daily fruit and vegetable consumption
and BMI. RESULTS: A significant, positive relationship was found between
perceived and observed availability of fruits and vegetables in the neighborhood
(r = 0.36, p<0.001). A similar relationship was seen between perceived and
observed quality of fruits and vegetables (r = 0.34, p<0.001). Perceived
availability and quality of fruits and vegetables in the neighborhood, and
availability and accessibility of fruits and vegetables in the home, were
significantly related to daily fruit and vegetable consumption. Perceived price
of food in the neighborhood was significantly associated with BMI. CONCLUSIONS:
Responses to a self-reported survey to assess perceived food environments related
to fruits and vegetables were significantly associated with observed nutrition
environments, fruit and vegetable consumption, and BMI. The perceived prices of
fruits and vegetables were modestly associated with BMI and warrant further
testing in prospective studies. When observations of food environments are not
feasible, residents' survey responses are an acceptable indicator, with
reasonable criterion validity.
PMID- 29338955
TI - Declining Health-Related Quality of Life in the U.S.
AB - INTRODUCTION: Despite recent declining mortality of the U.S. population from most
leading causes, uncertainty exists over trends in health-related quality of life.
METHODS: The 2001-2002 and 2012-2013 National Epidemiologic Surveys on Alcohol
and Related Conditions U.S. representative household surveys were analyzed for
trends in health-related quality of life (n=79,402). Health-related quality of
life was measured with the Short Form-6 Dimension scale derived from the Short
Form-12. Changes in mean Short Form-6 Dimension ratings were attributed to
changes in economic, social, substance abuse, mental, and medical risk factors.
RESULTS: Mean Short Form-6 Dimension ratings decreased from 0.820 (2001-2002) to
0.790 (2012-2013; p<0.0001). In regressions adjusted for age, sex,
race/ethnicity, and education, variable proportions of this decline were
attributable to medical (21.9%; obesity, cardiac disease, hypertension,
arthritis, medical injury), economic (15.6%; financial crisis, job loss),
substance use (15.3%; substance use disorder or marijuana use), mental health
(13.1%; depression and anxiety disorders), and social (11.2%; partner, neighbor,
or coworker problems) risks. In corresponding adjusted models, a larger
percentage of the decline in Short Form-6 Dimension ratings of older adults (aged
>=55 years) was attributable to medical (35.3%) than substance use (7.4%) risk
factors, whereas the reverse occurred for younger adults (aged 18-24 years; 5.7%
and 19.7%) and adults aged 25-44 years (12.7% and 16.3%). CONCLUSIONS: Between
2001-2002 and 2012-2013, there was a significant decline in average quality of
life ratings of U.S. adults. The decline was partially attributed to increases in
several modifiable risk factors, with medical disorders having a larger role than
substance use disorders for older adults but the reverse for younger and middle
aged adults.
PMID- 29338956
TI - Gender Identity Disparities in Cancer Screening Behaviors.
AB - INTRODUCTION: Transgender (trans) and gender-nonconforming adults have reported
reduced access to health care because of discrimination and lack of knowledgeable
care. This study aimed to contribute to the nascent cancer prevention literature
among trans and gender-nonconforming individuals by ascertaining rates of breast,
cervical, prostate, and colorectal cancer screening behaviors by gender identity.
METHODS: Publicly available de-identified data from the 2014-2016 Behavioral Risk
Factor Surveillance System surveys were utilized to evaluate rates of cancer
screenings by gender identity, while controlling for healthcare access,
sociodemographics, and survey year. Analyses were conducted in 2017. RESULTS:
Weighted chi-square tests identified significant differences in the proportion of
cancer screening behaviors by gender identity among lifetime colorectal cancer
screenings, Pap tests, prostate-specific antigen tests, discussing prostate
specific antigen test advantages/disadvantages with their healthcare provider,
and up-to-date colorectal cancer screenings and Pap tests (p<0.036). Weighted
logistic regressions found that although some differences based on gender
identity were fully explained by covariates, trans women had reduced odds of
having up-to-date colorectal cancer screenings compared to cisgender (cis) men
(AOR=0.20) and cis women (AOR=0.24), whereas trans men were more likely to ever
receive a sigmoidoscopy/colonoscopy as compared to cis men (AOR=2.76) and cis
women (AOR=2.65). Trans women were more likely than cis men to have up-to-date
prostate-specific antigen tests (AOR=3.19). Finally, trans men and gender
nonconforming individuals had reduced odds of lifetime Pap tests versus cis women
(AOR=0.14 and 0.08, respectively), and gender-nonconforming individuals had lower
odds of discussing prostate-specific antigen tests than cis men (AOR=0.09; all
p<0.05). CONCLUSIONS: The findings indicate that gender identity disparities in
cancer screenings persist beyond known sociodemographic and healthcare factors.
It is critical that gender identity questions are included in cancer and other
health-related surveillance systems to create knowledge to better inform
healthcare practitioners and policymakers of appropriate screenings for trans and
gender-nonconforming individuals.
PMID- 29338957
TI - Commuting and Sleep: Results From the Hispanic Community Health Study/Study of
Latinos Sueno Ancillary Study.
AB - INTRODUCTION: Commute time is associated with reduced sleep time, but previous
studies have relied on self-reported sleep assessment. The present study
investigated the relationships between commute time for employment and objective
sleep patterns among non-shift working U.S. Hispanic/Latino adults. METHODS: From
2010 to 2013, Hispanic/Latino employed, non-shift-working adults (n=760, aged 18
64 years) from the Sueno study, ancillary to the Hispanic Community Health
Study/Study of Latinos, reported their total daily commute time to and from work,
completed questionnaires on sleep and other health behaviors, and wore wrist
actigraphs to record sleep duration, continuity, and variability for 1 week.
Survey linear regression models of the actigraphic and self-reported sleep
measures regressed on categorized commute time (short: 1-44 minutes; moderate: 45
89 minutes; long: >=90 minutes) were built adjusting for relevant covariates. For
associations that suggested a linear relationship, continuous commute time was
modeled as the exposure. Moderation effects by age, sex, income, and depressive
symptoms also were explored. RESULTS: Commute time was linearly related to sleep
duration on work days such that each additional hour of commute time conferred 15
minutes of sleep loss (p=0.01). Compared with short commutes, individuals with
moderate commutes had greater sleep duration variability (p=0.04) and lower
interdaily stability (p=0.046, a measure of sleep/wake schedule regularity). No
significant associations were detected for self-reported sleep measures.
CONCLUSIONS: Commute time is significantly associated with actigraphy-measured
sleep duration and regularity among Hispanic/Latino adults. Interventions to
shorten commute times should be evaluated to help improve sleep habits in this
minority population.
PMID- 29338958
TI - Recommendations of the Second Panel on Cost Effectiveness in Health and Medicine:
A Reference, Not a Rule Book.
PMID- 29338959
TI - A new window into psychosis: The rise digital phenotyping, smartphone assessment,
and mobile monitoring.
AB - This commentary piece discusses recent advances in the use of mobile technologies
like smartphone and wearable sensors for schizophrenia research. By framing both
the opportunities as well as challenges for the field, this piece aims to frame
the both current and future research efforts.
PMID- 29338960
TI - Small-airway dysfunction precedes the development of asthma in children with
allergic rhinitis.
AB - BACKGROUND: Epidemiological evidence suggests the existence of a direct link
between allergic rhinitis (AR) and asthma. Several studies also support the
presence of small-airway dysfunction (SAD) in non-asthmatic children with AR.
However, it remains unknown whether SAD can predict the progression of AR to
asthma. Our objective was to explore the existence of SAD in non-asthmatic
children with AR and to assessed its ability to predict the development of
asthma. METHODS: Seventy-three 6-year-old children with intermittent moderate
severe AR but without asthma symptoms/medication within the last two years,
underwent spirometry and measurement of respiratory resistance (Rrs) and
reactance (Xrs) before and after bronchodilation (BD) (300mcg salbutamol). Lung
function measurements were performed in the absence of nasal symptoms and
repeated at AR exacerbation. SAD was defined as >30% decrease in Rrs or >50%
increase in Xrs at 6 or 8Hz post-BD. Participants were followed for five years.
RESULTS: Twenty-three children (31.5%) developed asthma; this group presented
significant post-BD changes in Rrs and Xrs, but only at AR exacerbation. The
ability of these changes to predict the development of asthma was exceptional and
superior to that of the spirometric parameters. SAD (22 children, 30.1%), emerged
as the single most efficient predictor of asthma, independently of other risk
factors such as parental asthma, personal history of eczema and type of allergic
sensitisation. CONCLUSION: SAD precedes the development of asthma in children
with AR. Changes in respiratory impedance at AR exacerbation may assist in
identifying those at risk to progress to asthma.
PMID- 29338961
TI - Is eosinophilic esophagitis an equivalent of pollen allergic asthma? Analysis of
biopsies and therapy guided by component resolved diagnosis.
AB - BACKGROUND: Eosinophilic esophagitis (EoE) is characterized by esophageal
dysfunction and, histologically, by eosinophilic inflammation. There is not a
clear etiologic treatment. Biopsies analysis using plant histology methods may
show callose and pollen tubes in the esophageal mucosa. Component-resolved
diagnosis (CRD) with microarrays could detect possible allergens involved and
indicate an elimination diet and allergen immunotherapy (AIT). METHODS: One
hundred and twenty-nine patients with EoE were tested for environmental and food
allergens. CRD, histological and botanical analysis were performed. Clinical
scores and endoscopic biopsy were performed every six months for three years.
Fifty healthy patients, 50 asthmatics due to pollen, and 53 celiac disease
patients were included as comparison groups. CRD-directed AIT was administered in
91 EoE patients and elimination diet in 140 patients (87 EoE and all 53 CD
patients). RESULTS: CRD detected allergen hypersensitivity in 87.6% of patients
with EoE. The predominant allergens were grass group 1 (55%), lipid transfer
proteins (LTP) of peach and mugwort, hazelnuts and walnuts. Callose from pollen
tubes was found in 65.6% of biopsies. After CRD-guided elimination diet and/or
AIT, 101 (78.3%) EoE patients showed significant clinical improvement (p<0.017)
and 97 (75.2%) were discharged (negative biopsy, no symptoms, no medication)
without relapse. AIT-treated patients had better outcomes (odds ratio 177.3, 95%
CI 16.2-1939.0). CONCLUSION: CRD-directed AIT and/or elimination diet was
efficient in treating EoE patients and was well tolerated.
PMID- 29338962
TI - Knowledge on asthma, food allergies, and anaphylaxis: Assessment of elementary
school teachers, parents/caregivers of asthmatic children, and university
students in Uruguaiana, in the state of Rio Grande do Sul, Brazil.
AB - INTRODUCTION: Allergic diseases have become an increasingly common reality in the
last years, extending beyond the family context. OBJECTIVE: Assessing the level
of knowledge on asthma, food allergies and anaphylaxis of asthmatic children's
parents/caregivers (PC), elementary school teachers (EST) and university students
(US) in Uruguaiana, RS, Brazil. METHOD: 577 individuals (PC - N=111; EST - N=177;
US - N=299) took part in the study, answering the Newcastle Asthma Knowledge
Questionnaire (validated for Portuguese) and another questionnaire on Food
Allergy (FA) and anaphylaxis. RESULTS: Although PC have asthmatic children, their
asthma knowledge level was average, slightly above that of EST and EU. The lack
of knowledge on passive smoking, use of medications and their side effects should
be highlighted. US have shown to be better informed about FA and anaphylaxis.
However, even though a significant proportion of respondents know the most common
symptoms of FA and anaphylaxis, few named subcutaneous adrenaline as the drug of
choice for treating anaphylaxis. Although a significant number of respondents
know about the possibility of anaphylactic reactions happening at school or in
activities outside the school, we were surprised by the absence of conditions in
schools to provide emergency care to such students. CONCLUSION: Despite the high
prevalence of allergic diseases in childhood, asthmatic children's
parents/caregivers, elementary school teachers and university students have
inadequate levels of knowledge to monitor these patients.
PMID- 29338963
TI - Loss of tolerance for fishes previously tolerated in children with fish food
protein induced enterocolitis syndrome.
AB - We describe two case reports presenting some novel information on fish FPIES.
Fish FPIES to one fish does not always start at the same time to other fish.
Additionally, development of tolerance to the index fish do not necessarily imply
tolerance to other reactive fish. This reflects on the best management of
children with FPIES fish.
PMID- 29338964
TI - Validation of the Children's Sleep Habits Questionnaire in a sample of Greek
children with allergic rhinitis.
AB - BACKGROUND: Obstructive respiratory disorders, such as allergic rhinitis and
asthma may impair sleep quality. The aim of this study is to validate the
Children's Sleep Habits Questionnaire (CSHQ) for Greek children from 6 to 14
years of age. No validated tool has been developed so far to assess sleep
disturbances in Greek school-aged children. METHODS: We examined the reliability
and validity of the CSHQ in a sample of children with allergic rhinitis (AR) and
a non-clinical population of parents of these children as a proxy measure of
children's AR quality of life (QoL) as evaluated by the Pediatric Allergic
Rhinitis Quality of Life (PedARQoL) questionnaire. RESULTS: The CSHQ
questionnaire Child's Form (CF) had a moderate internal consistency with a
Cronbach's alpha 0.671 and Guttman split-half coefficient of 0.563 when
correlated with the PedARQoL (CF). There was also a moderate intraclass
correlation of ICC=0.505 between the responses to both questionnaires in the two
visits. The CSHQ Parent's Form (PF) had a very good internal consistency with a
Cronbach's alpha of 0.928 and Guttman split-half coefficient of 0.798. There was
a high intraclass correlation of 0.643 between the responses in the two visits.
CONCLUSIONS: The Greek version of the CSHQ CF, but particularly the PF has proved
to be a very reliable clinical instrument, which can be used in clinical trials
for assessing sleep quality in school-aged children with sleep disturbances
because of obstructive airway disorders, such as AR.
PMID- 29338965
TI - Quality of life and clinical characterization of patients with vernal
keratoconjunctivitis in a pediatric population in Colombia.
AB - : Vernal keratoconjunctivitis is one of the most serious ocular allergies that
have the potential to induce large ocular morbidity and significant visual
changes affecting the quality of life of these individuals. METHODOLOGY: This
study was conducted in two phases. The first phase consisted of the clinical
characterization of 32 patients from the Clinical Allergology center of the
I.P.S. Universitaria from July 2014 to February 2015. A retrospective analysis of
medical records was performed. In the second phase, the evaluation of quality of
life was conducted using the questionnaire KIDSCREEN 27, which was validated in
our population and evaluated as recommended by the creators of this instrument.
RESULTS: A total of 24 patients (75%) were men, mean age of 12.1 (SD 2.6) years.
100% of the patients had clinical evaluation and were monitored by Allergology
and Ophthalmology, 12 patients (37.5%) were found in mild level, 5 patients
(15.6%) were moderate and 14 patients (43.8%) were severe level. The most common
symptoms were pruritus (75%), photophobia (50%), lacrimation (37.5%), and
secretions (28.1%). 65.6% had a family history of atopy and 84.4% had an allergic
comorbidity. Aeroallergen skin tests were found positive in 25 patients (78.1%).
All patients had initiated ocular treatment by the time the survey of quality of
life was conducted; but, they still had low quality of life scores in the 5
domains assessed. When the scores were evaluated by gender, the only
statistically significant difference was found in the domain of family life and
free time, which was lower for women. CONCLUSION: The vernal keratoconjunctivitis
is a disease more prevalent in men. It apparently has an important atopic base in
our environment, which due to its severe ocular involvement causes a marked
decrease in the quality of life of the children who present it.
PMID- 29338966
TI - Family history of venous thromboembolism predicts the diagnosis of acute
pulmonary embolism in the emergency department.
AB - BACKGROUND: Pulmonary embolism (PE) clinical decision rules do not consider a
patient's family history of venous thromboembolism (VTE). We evaluated whether a
family history of VTE predicts acute PE in the emergency department (ED).
METHODS: Over a 5.5-year study period, we enrolled a prospective convenience
sample of patients presenting to an academic emergency department with chest pain
and/or shortness of breath. We defined a family history of VTE as a first-degree
relative with previous PE or deep vein thrombosis (DVT). We noted outcomes of
testing during the patient's ED stay, including the diagnosis of acute PE by
either computed tomography (CT) or ventilation/perfusion (VQ) scan. RESULTS: Of
the 3024 study patients, 19.4% reported a family history of VTE and 1.9% were
diagnosed with an acute PE during the ED visit. Patients with a family history of
VTE were more likely to be diagnosed with a PE: 3.2% vs. 1.6% (p = 0.009). 82.3%
of patients were Pulmonary Embolism Rule-out Criteria (PERC) positive, and among
PERC-positive patients, those with a family history of VTE were more likely to be
diagnosed with a PE: 3.6% vs. 1.9% (p = 0.016). Of patients who underwent testing
for PE (33.7%), patients with a family history of VTE were more likely to be
diagnosed with a PE: 9.4% vs. 4.9% (p = 0.032). CONCLUSION: Patients with a self
reported family history of VTE in a first-degree relative are more likely to be
diagnosed with an acute PE in the ED, even among those patients considered to
have a higher likelihood of PE.
PMID- 29338967
TI - Real time optic nerve sheath diameter measurement during lumbar puncture.
AB - Measurement of optic nerve sheath diameter (ONSD) using point of care ultrasound
has been used to indirectly assess the intracranial pressure (ICP) particularly
in conditions where it is raised. Direct pressure measurements using probes
reaching the ventricle system correlated with ONSD using ultrasound. Attempts
were made to measure the ONSD pre and post lumbar puncture (LP) after draining
cerebrospinal fluid (CSF) as well as post ventricular shunt placement. We report
ONSD measurement and demonstrate dynamic changes during LP in a patient with
known idiopathic intracranial hypertension (IIH).
PMID- 29338968
TI - An alternative tool for triaging patients with possible acute coronary symptoms
before admission to a chest pain unit.
AB - OBJECTIVE: This study aimed to develop a triage tool to more effectively triage
possible ACS patients presenting to the emergency department (ED) before
admission to a protocol-driven chest pain unit (CPU). METHODS: Seven hundred
ninety-three clinical cases, randomly selected from 7962 possible ACS cases, were
used to develop and test an ACS triage model using cluster analysis and stepwise
logistic regression. RESULTS: The ACS triage model, logit (suspected ACS
patient)=-5.283+1.894*chest pain+1.612*age+1.222*male+0.958*proximal radiation
pain+0.962*shock+0.519*acute heart failure, with a threshold value set at 2.5,
was developed to triage patients. Compared to four existing methods, the chest
pain strategy, the Zarich's strategy, the flowchart, and the heart broken index
(HBI), the ACS triage model had better performance. CONCLUSION: This study
developed an ACS triage model for triaging possible ACS patients. The model could
be used as a rapid tool in EDs to reduce the workloads of ED nurses and
physicians in relation to admissions to the CPU.
PMID- 29338969
TI - Current and Future Challenges of Radiation Oncology in Iran: A Report from the
Iranian Society of Clinical Oncology.
AB - AIMS: Growth of the cancer incidence rate in Iran has been very high in recent
years. Therefore, the Iranian health care system should be prepared for the
treatment of a huge number of patients in the foreseeable future. One of the most
important treatment options for cancer is radiation. However, there is no
comprehensive information on infrastructure for radiation oncology in this
country. MATERIALS AND METHODS: In 2015, a questionnaire was designed by the
Iranian Society of Clinical Oncology (ISCO) and all radiation oncology centres in
the country were visited to determine four important components of radiation
oncology services, including facilities, equipment, personnel and patients.
RESULTS: In 2015, 94 radiotherapy centres were identified in Iran. Sixty-one
centres were fully operational, six centres were commissioning, 26 centres were
under construction and one was inactive. Among the fully operational radiotherapy
centres, 54 offered three-dimensional conformal radiotherapy and two-dimensional
radiotherapy, eight offered brachytherapy, two intensity-modulated radiotherapy,
two intraoperative radiotherapy, ostereotactic radiosurgery, two hyperthermia and
59 chemotherapy. Moreover, the survey identified 110 linear accelerators, 25
cobalt-60, one gamma knife, 21 remote brachytherapy afterloaders and six
orthovoltage units. Treatment planning equipment included 15 graphy simulators,
19 dedicated computed tomography simulators, 22 multileaf collimator and 12
electronic portal imaging devices. Moreover, in 2015, 243 clinical oncologists
participated in the treatment of 42 350 cancer patients in need of radiotherapy,
which is about one radiation oncologist for 175 patients. During 2010-2015,
number of cobalt-60 reduced 70%, from 25 units to 8 units. CONCLUSIONS: There is
a significant gap between Iran's available facilities for radiation therapy and
international standards. Moreover, during international economic sanctions
against Iran this gap widened.
PMID- 29338970
TI - Baicalein and baicalin alleviate acetaminophen-induced liver injury by activating
Nrf2 antioxidative pathway: The involvement of ERK1/2 and PKC.
AB - Acetaminophen (APAP)-induced hepatotoxicity is the main cause of drug-induced
liver injury. This study investigated the protection of baicalin and its aglycone
baicalein against APAP-induced hepatotoxicity and its mechanism. Baicalein and
baicalin alleviated APAP-induced hepatotoxicity both in vitro and in vivo.
Moreover, this baicalin-provided protection was not diminished in hepatocytes or
mice treated with beta-glucuronidase inhibitor. Results of liver glutathione
(GSH) and reactive oxygen species (ROS) formation demonstrated the alleviation of
baicalein and baicalin on APAP-induced liver oxidative stress injury. Baicalein
and baicalin induced the activation of nuclear factor erythroid 2-related factor
2 (Nrf2) and increased the expression of its downstream antioxidant genes.
Baicalein and baicalin-provided protection was diminished after the application
of Nrf2 siRNA in hepatocytes and Nrf2 knock-out mice. Molecular docking results
indicate the potential interaction of baicalein and baicalin with kelch-like ECH
associated protein-1 (Keap1). Baicalein and baicalin induced the sustained
phosphorylation of extracellular regulated protein kinases (ERK)1/2 and protein
kinase C (PKC). Moreover, ERK1/2 and PKC inhibitors both abrogated Nrf2
phosphorylation and its subsequent activation, and the protection against APAP
induced hepatotoxicity induced by baicalein and baicalin. In summary, baicalein
and baicalin alleviate APAP-induced hepatotoxicity by activating Nrf2 via
blocking the binding of Nrf2 with Keap1 and inducing Nrf2 phosphorylation. ERK1/2
and PKC are both critical for regulating the phosphorylation of Nrf2 induced by
baicalein or baicalin.
PMID- 29338971
TI - Atorvastatin impaired glucose metabolism in C2C12 cells partly via inhibiting
cholesterol-dependent glucose transporter 4 translocation.
AB - Skeletal muscle accounts for approximately 75% of glucose disposal in body and
statins impair glucose metabolism. We aimed to investigate the effect of
atorvastatin on glucose metabolism in C2C12 cells. Glucose metabolism and
expression of glucose transporter 4 (GLUT4) and hexokinase II (HXKII) were
measured following incubation with atorvastatin or pravastatin. Roles of
cholesterol in atorvastatin-induced glucose metabolism impairment were
investigated via adding cholesterol or mevalonic acid and confirmed by
cholesterol depletion with methyl-beta-cyclodextrin. Hypercholesterolemia mice
induced by high fat diet (HFD) feeding, orally received atorvastatin (6 and 12
mg/kg) or pravastatin (12 mg/kg) for 22 days. Results showed that atorvastatin
not pravastatin concentration-dependently impaired glucose consumption, glucose
uptake and GLUT4 membrane translocation in C2C12 cells without affecting
expression of HXKII or total GLUT4 protein. The atorvastatin-induced alterations
were reversed by cholesterol or mevalonic acid. Cholesterol depletion exerted
similar impact to atorvastatin, which could be alleviated by cholesterol
supplement. Glucose consumption or GLUT4 translocation was positively associated
with cellular cholesterol levels. In HFD mice, atorvastatin not pravastatin
significantly increased blood glucose levels following glucose or insulin dose
and decreased expression of membrane not total GLUT4 protein in muscle. Glucose
exposure following glucose or insulin dose was negatively correlated to muscular
free cholesterol concentration. Expression of membrane GLUT4 protein was
positively related to free cholesterol in muscle. In conclusion, atorvastatin
impaired glucose utilization in muscle cells partly via inhibiting GLUT4 membrane
translocation due to inhibition of cholesterol synthesis by atorvastatin, at
least, partly contributing to glucose intolerance in HFD mice.
PMID- 29338972
TI - HDL-C, ApoA1 and VLDL-TG as biomarkers for the carotid plaque presence in
patients with metabolic syndrome.
AB - AIM: Hypercholesterolemia and hyper LDL-C are associated with the atherosclerosis
(AS). The current study was performed to evaluate the implication of the others
lipoproteins (HDL, LDL, VLDL) and apolipoproteins (ApoA1, ApoB100) with
subclinical atherosclerosis (carotid plaque) in patients with metabolic syndrome
(MetS) free from cardiovascular disease (CVD). METHODS: Prospective transversal
study was conducted in patients with MetS free from cardiovascular disease (CVD).
The lipids, lipoproteins and apolipoproteins were measured. The lipoproteins
(HDL, LDL, VLDL) were obtained by the precipitation method. The carotid plaque
(CP) was evaluated by ultrasonography, method for assessing AS. Logistic
regression and analysis tree were used to look for the association and the
incrimination of the lipoproteins with the presence of CP. RESULTS: The CP
incidence was 60% among the participants, 34.29% on the right and the left plaque
against 25.71% for only one plaque. The HDL-C was the only lipoprotein associated
with the CP after adjustment of the age, the sex and BMI (OR: 0.007 P: 0.046)
with the logistic regression analysis, HDL-C (<0.35 g/l), ApoA1 (<1.43 g/l) and
VLDL-TG (>0.656 g/l) are implicated in the presence of CP with the analysis tree
analysis. CONCLUSION: Lower level of HDL-C is associated with CP, HDL-C, ApoA1,
and high level VLDL-TG but not total cholesterol, and LDL-Care useful parameters
in the assessment of initial atherosclerosis in metabolic syndrome.
PMID- 29338973
TI - Asthma-COPD overlap: A Portuguese survey.
AB - INTRODUCTION: The overlap between asthma and chronic obstructive pulmonary
disease (COPD) (ACO) has been discussed for many years but clinical
recommendations for this entity have been diverse. This study is intended to
reach a consensus on diagnosis, treatment and patient orientation for ACO, within
the Portuguese medical community. METHODS: This study was conducted by a
multidisciplinary panel of experts from three distinct medical specialties
(Pulmonology, Family Medicine and Immunoallergology). This panel selected a total
of 190 clinicians, based on their expertise in obstructive airway diseases, to
participate in a Delphi structured survey with three rounds of questionnaires.
These results were ultimately discussed, in a meeting with the panel of experts
and some of the study participants, and consensus was reached in terms of
classification criteria, treatment and orientation of ACO patients. RESULTS: The
majority of clinicians (87.2%) considered relevant the definition of an overlap
entity between asthma and COPD. A consensus was achieved on the diagnosis of ACO
presence of simultaneous clinical characteristics of asthma and COPD together
with a fixed airflow obstruction (FEV1/FVC<0.7) associated with 2 major criteria
(previous history of asthma; presence of a previous history of smoking exposure
and/or exposure to biomass combustion; positive bronchodilation test (increase in
FEV1 of at least 200mL and 12%) on more than 1 occasion) plus 1 minor criteria
(history of atopy; age >=40 years; peripheral eosinophilia (>300eosinophils/MUL
or >5% of leukocytes); elevation of specific IgEs or positive skin tests for
common allergens). A combination of inhaled corticosteroid (ICS) with long-acting
beta2-agonist (LABA) or long-acting muscarinic antagonist (LAMA) was considered
as first line pharmacological treatment. Triple therapy with ICS plus LABA and
LAMA should be used in more severe or symptomatic cases. Non-pharmacological
treatment, similar to what is recommended for asthma and COPD, was also
considered highly important. A hospital referral of ACO patients should be made
in symptomatic or severe cases or when there is a lack of diagnostic resources.
CONCLUSIONS: This study highlights the relevance of defining ACO, within the
Portuguese medical community, and establishes diagnostic criteria that are
important for future interventional studies. Recommendations on treatment and
patient's orientation were also achieved.
PMID- 29338974
TI - Usefulness of the "grand-piano sign" for determining femoral rotational alignment
in total knee arthroplasty.
AB - BACKGROUND: The "grand-piano sign" is a well-known indicator of proper rotational
femoral alignment. We investigated changes in the shape of the femoral anterior
cutting plane by changing the rotational alignment, anterior portion depth, and
cutting plane flexion angle. METHODS: We simulated various cutting planes after
cutting the anterior portion of the femur next to the distal femoral osteotomy in
50 patients with varus knee and also a femoral anterior osteotomy with four
degree (S group) and seven degree (T group) flexion angles regarding the
mechanical axis. We defined the final cutting plane as the farthest position that
we could reach without making a notch and the precutting plane as two millimeters
anterior from the final cutting plane. The simulated resection plane was rotated
to produce external and internal rotation angles of 0 degrees , three degrees,
and five degrees relative to the surgical transepicondylar axis (SEA). We
investigated medial and lateral portions of the femoral anterior cutting plane
length ratio (M/L). RESULTS: When we cut parallel to SEA, M/L was 0.67+/-0.09 and
0.62+/-0.12 in the T and S groups, respectively. M/L was approximately 0.8 and
0.5 with five degree internal and external rotations, respectively (P<0.01). On
comparing final cutting and precutting planes, there were no significant
differences in M/L without five degree external rotation in the T group and no
significant difference in any case in the S group (P>0.01). CONCLUSIONS: The
ideal M/L of the femoral anterior cutting plane was 0.62-0.67. M/L did not change
with a precutting plane in almost all rotational patterns.
PMID- 29338976
TI - WASP (Write a Scientific Paper) using Excel - 4: Histograms.
AB - Plotting data into graphs is a crucial step in data analysis as part of an
initial descriptive statistics exercise since it gives the researcher an overview
of the shape and nature of the data. Outlier values may also be identified, and
these may be incorrect data, or true and important outliers. This paper explains
how to access Microsoft Excel's Analysis Toolpak and provides some pointers for
the utilisation of the histogram tool within the Toolpak.
PMID- 29338975
TI - Critical effects of polar fluorescent probes on the interaction of DHA with POPC
supported lipid bilayers.
AB - The understanding of lipid bilayer structure and function has been advanced by
the application of molecular fluorophores. However, the effects of these probe
molecules on the physicochemical properties of membranes being studied are poorly
understood. A quartz crystal microbalance with dissipation monitoring instrument
was used in this work to investigate the impact of two commonly used fluorescent
probes, 1-palmitoyl-2-{12-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]dodecanoyl}-sn
glycero-3-phosphocholine (NBD-PC) and 1,2-dipalmitoyl-sn-glycero-3
phosphoethanolamine-n-(lissamine rhodamine-B-sulfonyl) (Lis-Rhod PE), on the
formation and physicochemical properties of a 1-palmitoyl-2-oleoyl-sn-glycero-3
phosphocholine supported lipid bilayer (POPC-SLB). The interaction of the POPC
SLB and fluorophore-modified POPC-SLB with docosahexaenoic acid, DHA, was
evaluated. The incorporation of DHA into the POPC-SLB was observed to
significantly decrease in the presence of the Lis-Rhod PE probe compared with the
POPC-SLB. In addition, it was observed that the small concentration of DHA
incorporated into the POPC:NBD-PC SLB can produce rearrangement processes
followed by the lost not only of DHA but also of POPC or NBD-PC molecules or both
during the washing step. This work has significant implications for the
interpretation of data employing fluorescent reporter molecules within SLBs.
PMID- 29338977
TI - WASP (Write a Scientific Paper) using Excel - 2: Pivot tables.
AB - Data analysis at the descriptive stage and the eventual presentation of results
requires the tabulation and summarisation of data. This exercise should always
precede inferential statistics. Pivot tables and pivot charts are one of Excel's
most powerful and underutilised features, with tabulation functions that
immensely facilitate descriptive statistics. Pivot tables permit users to
dynamically summarise and cross-tabulate data, create tables in several
dimensions, offer a range of summary statistics and can be modified interactively
with instant outputs. Large and detailed datasets are thereby easily manipulated
making pivot tables arguably the best way to explore, summarise and present data
from many different angles. This second paper in the WASP series in Early Human
Development provides pointers for pivot table manipulation in ExcelTM.
PMID- 29338978
TI - Non-risk-adapted Surveillance for Stage I Testicular Cancer: Critical Review and
Summary.
AB - CONTEXT: Cancer-specific survival for men with clinical stage I testicular cancer
(CSITC) is uniformly excellent. Non-risk-adapted active surveillance (NRAS) is a
management strategy for CSITC to minimize overtreatment and avoid possible long
term side effects of adjuvant therapy. OBJECTIVE: To review the evidence
regarding oncologic outcomes for men with CSITC undergoing NRAS and discuss
ongoing controversies in the management of CSITC. EVIDENCE ACQUISITION:
MEDLINE/PubMed, Embase, and the Cochrane Central Register of Controlled Trials
were searched from January 1, 1987 through January 1, 2017. EVIDENCE SYNTHESIS: A
total of 68 studies were included in the critical review. The rationale for NRAS,
oncologic outcomes, surveillance protocols, and comparative efficacy of risk
adjusted active surveillance (AS) were reported with strength of evidence and
risk of bias evaluated. Cancer-specific survival approaches 100% for men with
CSITC undergoing NRAS. Active treatment is limited to 20-30% of patients who will
recur; these patients will require salvage chemotherapy and possible
retroperitoneal lymph node dissection. Existing AS protocols include imaging and
laboratory evaluations that are initially intensive but less frequent with
increasing follow-up. CONCLUSIONS: NRAS is an attractive management option for
men with CSITC, which maintains outstanding long-term cancer cure while sparing
most patients treatment by avoiding prophylactic chemotherapy, radiation, or
surgery. PATIENT SUMMARY: Men with clinically localized (stage I) testicular
cancer have an excellent prognosis, regardless of management. Non-risk-adapted
active surveillance is an attractive management option where only patients
destined to relapse will receive any treatment following orchiectomy. However,
individual patient preferences should be discussed in selecting a management
strategy.
PMID- 29338979
TI - Dysregulated autophagy in restrictive cardiomyopathy due to Pro209Leu mutation in
BAG3.
AB - Myofibrillary myopathies (MFM) are hereditary myopathies histologically
characterized by degeneration of myofibrils and aggregation of proteins in
striated muscle. Cardiomyopathy is common in MFM but the pathophysiological
mechanisms are not well understood. The BAG3-Pro209Leu mutation is associated
with early onset MFM and severe restrictive cardiomyopathy (RCM), often
necessitating heart transplantation during childhood. We report on a young male
patient with a BAG3-Pro209Leu mutation who underwent heart transplantation at
eight years of age. Detailed morphological analyses of the explanted heart tissue
showed intracytoplasmic inclusions, aggregation of BAG3 and desmin,
disintegration of myofibers and Z-disk alterations. The presence of undegraded
autophagosomes, seen by electron microscopy, as well as increased levels of p62,
LC3-I and WIPI1, detected by immunohistochemistry and western blot analyses,
indicated a dysregulation of autophagy. Parkin and PINK1, proteins involved in
mitophagy, were slightly increased whereas mitochondrial OXPHOS activities were
not altered. These findings indicate that altered autophagy plays a role in the
pathogenesis and rapid progression of RCM in MFM caused by the BAG3-Pro209Leu
mutation, which could have implications for future therapeutic strategies.
PMID- 29338980
TI - Prevalence of Bovine Aortic Arch Variant in Patients with Aortic Dissection and
its Implications in the Outcome of Patients with Acute Type B Aortic Dissection.
AB - OBJECTIVE/BACKGROUND: To investigate the prevalence of bovine arch (BA) among
patients with type A and B aortic dissection, and to provide insight into the
implication of this variation on the outcome of patients with acute or subacute
type B aortic dissection (a/sTBAD). METHODS: This retrospective cohort analysis
includes patients with a/sTBAD admitted between January 2006 and December 2016.
Computed tomographic angiograms (CTAs) of patients referred because of type A
aortic dissection were also re-evaluated with regard to the presence of BA. As a
control group, 110 oncological patients who had undergone a chest CTA for disease
staging during the study period were enrolled. A total of 154 patients with
a/sTBAD and 168 with type A aortic dissection were identified during the study
period. RESULTS: An overall prevalence of 17.6% for BA variants was revealed. The
comparison between patients with aortic dissection and the control group showed
no statistically significant difference in BA prevalence (17.7% vs. 17.3%; p =
1.0). No statistically significant difference in BA prevalence was observed when
comparing patients with type A aortic dissection with those with type B aortic
dissection (16.6% vs. 18.8%; p = .66). During a median follow-up period of 27.8
months, 30 patients died. The mortality rate among patients presenting a BA
variant was 34.5%, whereas among patients without, it was 16.0% (p = .04).
Multivariate analysis revealed the presence of a BA as an independent predictor
of mortality (adjusted odds ratio 3.4, 95% confidence interval 1.2-9.8).
CONCLUSION: The BA should be considered as a predictor of the outcome for
patients with type B aortic dissection.
PMID- 29338981
TI - Reproducibility and agreement of different non-invasive methods of endothelial
function assessment.
AB - Flow-mediated dilatation (FMD) is an established, but investigator-demanding
method, used to non-invasively determine nitric oxide (NO)-dependent endothelial
function in humans. Local thermal hyperemia (LTH) or post-occlusive reactive
hyperemia (PORH) of the skin measured with a laser Doppler flow imager may be a
less demanding alternative of FMD. We investigated the reproducibility of the
different measures of vascular function, their interrelationship and the NO
dependency of LTH. Measurements were performed twice in 27 healthy men (8
smokers), one week apart. Local application of NG-monomethyl-l-arginine (L-NMMA)
by means of iontophoresis was used to determine the NO-dependency of LTH. Using L
NMMA, the peak and plateau responses of LTH were reduced by 31% (p < .001) and
65% (<0.001), respectively. For all measurements the coefficient of variation
(CV) was higher in smokers than in non-smokers. For non-smokers the CV of FMD was
12%, of LTH peak response 17%, of LTH plateau response 12%, of PORH peak response
14% and of PORH area under the curve response 11%. FMD correlated weakly with the
PORH peak and area under the curve response (r = 0.39 and 0.43, p < .05), whereas
the LTH-plateau response correlated with the PORH peak response (r = 0.68, p <
.01) in non-smokers, but FMD and LTH peak or plateau responses were unrelated. In
conclusion, the LTH plateau response is for two-third NO-dependent, but unrelated
to FMD. Furthermore, despite easy to perform the LTH responses are not more
reproducible than FMD. Given the weak associations, the different methods of
vascular function assessment are not interchangeable.
PMID- 29338982
TI - Involvement of peripheral alpha2A adrenoceptor in the acceleration of
gastrointestinal transit and abdominal visceral pain induced by intermittent
deprivation of REM sleep.
AB - Many studies have associated sleep alterations with the severity of irritable
bowel syndrome (IBS) symptoms, but the direct pathophysiological relationship has
not been clarified. In addition, alterations in noradrenergic signaling have been
implicated in the pathophysiology of IBS, and alpha2-adrenoceptors are potential
treatment targets. We have previously shown that acceleration of gastrointestinal
transit (GIT) elicited by intermittent rapid eye movement (REM) sleep deprivation
stress may fulfill the profile of a model of IBS. Moreover, we showed
hypernoradrenergic function in the brain of sleep-deprived mice. On the other
hand, acetic acid-induced writhes indicate visceral pain features of IBS model
animals. In this study, using mice, we investigated whether intermittent REM
sleep deprivation stress causes changes in acetic acid-induced writhing and
whether the number of writhes and GIT are improved by administration of the
hydrophilic clonidine analogue, ST-91. Mice were deprived of REM sleep
intermittently using the small-platform method (20h/day) for 3days. The
intermittent REM sleep deprivation stress elicited acceleration of GIT and the
increased number of writhes was significantly improved by ST-91 treatment. The
ID50 values of ST-91 on the GIT in cage-control mice and intermittent REM sleep
deprived mice were 0.24 and 0.70mg/kg, respectively. In addition, the ID50 values
of ST-91 on the writhes in cage-control mice and intermittent REM sleep-deprived
mice were 0.52 and 0.73mg/kg, respectively. Further, the expression of alpha2A
adrenoceptor was decreased in the distal ileum of intermittent REM sleep-deprived
mice compared to that in cage-control mice. Moreover, the effects of ST-91 on GIT
and writhes in cage-control and intermittent REM sleep-deprived mice were
decreased by the administration of BRL44408 (6mg/kg, i.p.), a selective alpha2A
adrenoceptor antagonist, and not by the administration of imiloxan (3mg/kg,
i.p.), or JP-1302 (3mg/kg, i.p.), selective alpha2B-and alpha2C-adrenoceptor
antagonists, respectively. These results suggest that the increase in GIT and
writhes induced by intermittent REM sleep deprivation stress may serve as a model
of diarrhea and visceral pain symptoms in IBS. Further, the onset of these
symptoms may be related to the hypofunction of peripheral alpha2A-adrenoceptor.
PMID- 29338983
TI - Dipyridamole plus Triflusal versus Triflusal Alone in Infarct Reduction after
Middle Cerebral Artery Occlusion.
AB - BACKGROUND AND PURPOSE: The objective of this work is to study the dose-dependent
effect of combination therapy with dipyridamole and triflusal over that of
triflusal alone on infarct size after middle cerebral artery occlusion (MCAO)
ischemia. MATERIALS AND METHODS: Male Wistar rats were subjected to a permanent
MCAO in the right hemisphere. Rats received triflusal alone and with dipyridamole
via oral route. Three days after surgery, infarct volumes were measured. RESULTS:
The lower dose regime of triflusal (10 mg/kg) and dipyridamole (200 mg/kg) caused
the greatest decrease in infarct size compared with higher dose regime of
triflusal (30 mg/kg) and dipyridamole (200 mg/kg) (P <.01), triflusal (30 mg/kg)
alone (P <.07), and vehicle-treated controls. CONCLUSIONS: The lower dose
combination of dipyridamole and triflusal appears to be more effective than
triflusal alone after MCAO-induced cerebral ischemia. Therefore, there is a
strong rationale to continue to examine the protective effects of triflusal and
dipyridamole after cerebral ischemia.
PMID- 29338984
TI - Practical guidelines for performing laparoscopic liver resection based on the
second international laparoscopic liver consensus conference.
AB - Laparoscopic liver resection is rapidly increasing, and certain types of
resection are considered standard procedures for liver resection, especially for
small malignant tumors located on the liver surface or in the anterolateral
segments of the liver. Several specialized centers have performed many types of
highly complex hepatectomies, anatomical resections, and laparoscopic donor
hepatectomies. Even though several international consensus conferences and expert
meetings have been held, until now there have been no practical guidelines for
beginners or experts conducting laparoscopic liver resection. We describe here
practical guidelines for performing laparoscopic liver resection, including the
indications, technical considerations, and training required.
PMID- 29338985
TI - The shikimate pathway enzyme that generates chorismate is not required for the
development of Plasmodium berghei in the mammalian host nor the mosquito vector.
AB - In Plasmodium, the shikimate pathway is a potential target for malaria
chemotherapy owing to its absence in the mammalian host. Chorismate, the end
product of this pathway, serves as a precursor for aromatic amino acids, Para
aminobenzoic acid and ubiquinone, and is synthesised by Chorismate synthase (CS).
Therefore, it follows that the Cs locus may be refractory to genetic
manipulation. By utilising a conditional mutagenesis system of yeast Flp/FRT, we
demonstrate an unexpectedly dispensable role of CS in Plasmodium. Our studies
reiterate the need to establish an obligate reliance on Plasmodium metabolic
enzymes through genetic approaches before their selection as drug targets.
PMID- 29338986
TI - Mismanagement of Severe Altitude Illness in a Tertiary Hospital in Nepal: A
Cautionary Tale.
PMID- 29338987
TI - Update on the Epidemiology of Scorpion Envenomation in the South of Tunisia.
AB - INTRODUCTION: Scorpion envenomation is still a frequent occurance in tropical and
subtropical regions. In Tunisia, multiple studies on scorpion envenoming have
contributed to an improved understanding of cardiac dysfunction and factors
predictive of poor prognosis. These previous studies have contributed to the
current standardized management of envenomed patients. However, the epidemiology
of scorpion envenoming in Tunisia has not been updated for more than 10 years.
The aim of this study was to report an update of the epidemiological features of
scorpion envenomation in the southern region of Tunisia. METHODS: This is a
retrospective monocentric study including all patients admitted in the emergency
room for scorpion envenomation. Cases were collected from emergency medical files
during a 3-year period (2013-2015). The diagnosis of scorpion envenomation was
made by history of a scorpion sting. All files in which scorpion envenomation was
not certain were excluded. Data are presented as mean+/-SD with range or
percentages, as appropriate. RESULTS: We enrolled 282 patients aged 27.4+/-22.8
years with a 1:1 sex ratio. During surveillance in the emergency room, 39
patients developed cardiac dysfunction. Overall, 42 patients (14.9%) were at
stage 3 of severity, and 240 patients (85.1%) had moderate scorpion envenomation
(stage 2). Only 1 patient died a few hours after admission. In the remaining
cases, the outcome was good. Our results show the improvement in mortality rates
even in severe presentations. CONCLUSION: This study found that the outcome of
scorpion-stung patients has clearly improved. This enhancement can be explained
by early medical consultation and standardized management of patients with
predictive factors for cardiac dysfunction.
PMID- 29338988
TI - Acetazolamide Use in Ultrarunners at Altitude: Issues with Doping.
PMID- 29338989
TI - Relations Between Self-Reported and Linguistic Monitoring Assessments of
Affective Experience in an Extreme Environment.
AB - INTRODUCTION: Approaches for monitoring psychosocial health in challenging
environments are needed to maintain the performance and safety of personnel. The
purpose of the present research was to examine the relationship between 2
candidate methods (self-reported and linguistics) for monitoring affective
experience during extreme environment activities. METHODS: A single-subject
repeated-measures design was used in the present work. The participant was a 46
year-old individual scheduled to complete a self-supported ski expedition across
Arctic Greenland. The expedition lasted 28 days, and conditions included severe
cold, low stimulation, whiteouts, limited habitability, and threats to life and
limb. During the expedition, the participant completed a daily self-report log
including assessment of psychological health (perceptions of control and affect)
and a video diary (emotion). Video diary entries were subjected to linguistic
inquiry and word count analyses before the links between self-report and
linguistic data across the expedition period were tested. RESULTS: Similarities
in the pattern of self-reported and linguistic assessments emerged across the
expedition period. A number of predictable correlations were identified between
self-reported and linguistic assessments of affective/emotional experience.
Overall, there was better agreement between self-reports and linguistic analytics
for indicators of negative affect/emotion. CONCLUSIONS: Future research should
build on this initial study to further test the links between self-reported
affect and emotional states monitored via linguistics. This could help develop
methods for monitoring psychological health in extreme environments and support
organizational decision making.
PMID- 29338991
TI - Jellyfish Blooms Causing Mass Envenomations in Aquatic Marathonists: Report of
Cases in S and SE Brazil (SW Atlantic Ocean).
PMID- 29338990
TI - Frequency of Polycythemia and Other Abnormalities in a Tibetan Herdsmen
Population Residing in the Kham Area of Sichuan Province, China.
AB - INTRODUCTION: The Kham Tibetans are one of several Tibetan ethnic subgroups
living in the Kham area of China. Because studies on the high-altitude adaptation
of the Kham people are scant, the main aim of this study is to investigate
whether the response to hypoxia, especially polycythemia status, in the Kham
Tibetans is different from other Tibetan ethnic subgroups. METHODS: The primary
investigation was conducted on 346 native Kham Tibetan adults (268 men and 78
women) from 3 herdsmen villages located in Hongyuan County situated at an
altitude of greater than 3600 m. The participants were aged 46.2+/-14.1 (21-82;
mean+/-SD with range) years. Anthropometric measurements such as weight, height,
waist circumference, body mass index, and blood pressure, as well as laboratory
blood tests such as glycosylated hemoglobin, hemoglobin, total cholesterol,
triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein
cholesterol, and uric acid were analyzed. RESULTS: The concentrations of
hemoglobin were 171.3+/-12.9 (66-229) mg.L-1 and 151.4+/-16.4 (86-190) mg.L-1 in
men and women, respectively. The frequency of polycythemia was found to be 25.5
and 21.8% in men and women, respectively. Polycythemia was found to be
significantly associated with glycosylated hemoglobin concentrations,
hypertension, and hyperuricemia (P=0.002, 0.023, and 0.009, respectively).
CONCLUSIONS: There is a higher frequency of polycythemia in the Kham Tibetans
when compared with reported studies from other Tibetan ethnic subgroups living on
the Qinghai-Tibet plateau.
PMID- 29338992
TI - Subsequent fertility, pregnancy, and gynecologic outcomes after fetoscopic laser
therapy for twin-twin transfusion syndrome compared with normal monochorionic
twin gestations.
AB - BACKGROUND: An improved survival and quality of life for neonatal survivors after
fetoscopic laser therapy for twin-twin transfusion syndrome has been reported.
However, little is known about the medium-term maternal effects after fetoscopic
laser therapy with respect to reproductive and gynecologic outcomes. OBJECTIVE:
The objective of this study was to document reproductive, obstetric,
gynecological, and psychological outcomes in women who underwent fetoscopic laser
therapy for twin-twin transfusion syndrome. STUDY DESIGN: This was a monocentric
controlled study on consecutive women who underwent fetoscopic laser therapy for
twin-twin transfusion syndrome between 2007 and 2013 at the University Hospitals
Leuven (cases; n = 198). Controls were women followed up during the same time
period for an uncomplicated monochorionic diamniotic twin pregnancy and with an
uneventful course (controls; n = 211). All patients received a questionnaire
inquiring on their fertility, later pregnancies, and gynecological outcomes.
RESULTS: The response rate was 50.4% (cases: n = 95; controls: n = 109). Most
baseline characteristics were similar across both groups. Women in the fetoscopic
laser therapy group attempted a new pregnancy more frequently (34% [31 of 92] vs
21% [22 of 107] in controls; P < .05) and became pregnant more often (100% [31 of
31] vs 82% [18 of 22]; P < .05).We observed a shorter interpregnancy interval in
cases than controls (median interval, 12 [interquartile range, 5-27] vs 24
[interquartile range, 15-30] months) (P < .05). This was also observed in cases
who lost one or both fetuses or babies in the index pregnancy (median interval, 9
[interquartile range, 3.5-25.5] months; P < .05). The complication rate during
subsequent pregnancies (26% [8 of 31] vs 11% [2 of 19]; P = .194) and at delivery
(17% [5 of 30] vs 11% [2 of 19]; P = .554) were comparable. More women who
underwent fetoscopic laser coagulation reported relevant psychological symptoms
(44% [40 of 92] vs 21% [23 of 107]; P < .05). When only women in whom there was a
double-surviving twin pair were considered, there were no differences in
psychological symptoms compared with controls (16% [15 of 55] vs 21% [23 of 107];
P = .411). Gynecological problems were equally frequent in both groups (20% [18
of 92] vs 31% [33 of 107]; P = .069). CONCLUSION: No adverse medium-term maternal
effects with respect to fertility, obstetric, and gynecological outcomes were
observed after fetoscopic laser therapy. However, these women reported more
psychological or emotional problems than women with monochorionic diamniotic who
did not have laser therapy, in particular when this was complicated by a fetal
loss.
PMID- 29338993
TI - Peritoneal sarcomatosis 5 years after laparoscopic morcellation of uterine
leiomyoma.
PMID- 29338994
TI - Both patients and maternity care providers can benefit from payment reform: four
steps to prepare.
AB - Many Medicaid programs and private health plans are implementing new models of
maternity care reimbursement, and clinicians face mounting pressure to
demonstrate high-quality care at a lower cost. Clinicians will be better prepared
to meet these challenges with a fuller understanding of new payment models and
the opportunities they present. We describe the structure of maternity care
episode payments and recommend 4 ways that clinicians can prepare for success as
value-based payment models are implemented: identify opportunities to improve
outcomes and experience, measure quality, reduce waste, and work in teams across
settings.
PMID- 29338995
TI - Echocardiography as a Clinical Stratification Tool in Venovenous Extracorporeal
Membrane Oxygenation.
PMID- 29338996
TI - Incidence and Predictors of Postoperative Need for High-Dose Inotropic Support in
Patients Undergoing Cardiac Surgery for Infective Endocarditis.
AB - OBJECTIVE: Patients with infective endocarditis undergoing cardiac surgery are a
high-risk population. Few data on incidence and predictors of need for high-dose
inotropic support in this setting are currently available. DESIGN: Retrospective
study. SETTING: Tertiary-care hospital. PARTICIPANTS: Ninety consecutive patients
undergoing cardiac surgery for infective endocarditis. INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: Baseline, intraoperative and outcome data were
collected. Stepwise multiple logistic regression analysis was performed to
identify preoperative predictors of postoperative hemodynamic support. High-dose
postoperative inotropic support was defined as inotropic score >10 (calculated as
dobutamine dose (in ug/kg/min) + dopamine dose (in ug/kg/min) + (epinephrine dose
[in ug/kg/min] * 100) + (norepinephrine dose [in ug/kg/min] * 100) + (milrinone
dose [in ug/kg/min] * 10) + (vasopressin dose [in U/kg/min] * 10 000) +
(levosimendan dose [in ug/kg/min] * 50) or need for mechanical circulatory
support at intensive care unit admission. Postoperative high-dose inotropic or
mechanical circulatory support was required in 57 cases (61%). Stepwise multiple
logistic regression identified 5 variables independently associated with need for
postoperative circulatory support: male sex (odds ratio [OR] = 10.9), surgery
duration (OR for every minute increase = 1.01), impairment of kidney function
(eGFR <60 mL/min/m2 - OR = 19), preoperative new-onset heart failure (defined by
clinical, imaging and laboratory parameters - OR = 5.30), and low preoperative
platelet count (for every 1*103/MUl increase - OR = 0.99). CONCLUSIONS: Patients
undergoing cardiac surgery for infective endocarditis are at high risk for
postoperative hemodynamic instability. Preoperative organ failure is an important
determinant for postoperative hemodynamic instability.
PMID- 29338997
TI - Meta-analysis of the Sources of Bleeding after Adult Cardiac Surgery.
AB - OBJECTIVE: The aim of this study was to pool data on the proportion and
prognostic impact of sources of bleeding in patients requiring re-exploration
after adult cardiac surgery. DESIGN: Systematic review of the literature and meta
analysis. SETTING: Multistitutional study. MEASUREMENTS AND MAIN RESULTS: A
literature review was performed to identify studies published since 1990
evaluating the outcome after reoperation for bleeding or tamponade after adult
cardiac surgery. Eighteen studies including 5,1497 patients fulfilled the
selection criteria. Reoperation for bleeding/tamponade was performed in 2,455
patients (4.6%; 95% confidence interval [CI] 3.9%-5.2%, I2 92%). These had a
significantly higher risk of in-hospital/30-day mortality compared with patients
not reoperated for bleeding (pooled rates: 9.3% v 2.3%; risk ratio 3.30; 95% CI
2.52-4.32; I2 47%; 8 studies; 25,463 patients). Surgical sites of bleeding were
identified in 65.7% of cases (95% CI 58.3%-73.2%; I2 94%), cardiac site bleeding
in 40.9% of cases (95% CI 29.7%-52.0%; I2 94%), and mediastinal/sternum site
bleeding in 27.0% of cases (95% CI 16.8%-37.3%; I2 94%). The main sites of
bleeding were the body of the graft (20.2%), the sternum (17.0%), vascular
sutures (12.5%), the internal mammary artery harvest site (13.0%), and
anastomoses (9.9%). In metaregression, surgical site bleeding was associated with
a lower risk of in-hospital/30-day mortality compared with diffuse bleeding (p =
0.003). CONCLUSIONS: Surgical site bleeding is identified in two-thirds of
patients undergoing re-exploration after adult cardiac surgery. Meticulous
surgical technique and systematic intraoperative checking of potential surgical
sites of bleeding at the time of the original cardiac surgery may reduce the risk
of such a severe complication.
PMID- 29338998
TI - General Anesthesia Versus Conscious Sedation for Transcatheter Aortic Valve
Replacement-An Analysis of Current Outcome Data.
PMID- 29338999
TI - Implantable Left Ventricular Assist Device Therapy-Recent Advances and Outcomes.
PMID- 29339000
TI - A New Way to Secure Internal Jugular Central Catheters.
PMID- 29339001
TI - Does the surgical approach for treating mandibular condylar fractures affect the
rate of seventh cranial nerve injuries? A systematic review and meta-analysis
based on a new classification for surgical approaches.
AB - PURPOSE: The purpose of this study was to determine the rate of facial nerve
injury (FNI) when performing (ORIF) of mandibular condylar fractures by different
surgical approaches. MATERIALS AND METHODS: A systematic review and meta-analysis
were performed that included several databases with specific keywords, a
reference search, and a manual search for suitable articles. The inclusion
criteria were all clinical trials, with the aim of assessing the rate of facial
nerve injuries when (ORIF) of mandibular condylar fractures was performed using
different surgical approaches. The main outcome variable was transient facial
nerve injury (TFNI) and permanent facial nerve injury (PFNI) according to the
fracture levels, namely: condylar head fractures (CHFs), condylar neck fractures
(CNFs), and condylar base fractures (CBFs). For studies where there was no
delineation between CNFs and CBFs, the fractures were defined as CNFs/CBFs. The
dependent variables were the surgical approaches. RESULTS: A total of 3873
patients enrolled in 96 studies were included in this analysis. TFNI rates
reported in the literature were as follows: A) For the transoral approach: a) for
strictly intraoral 0.72% (1.3 in CNFs and 0% for CBFs); b) for the transbuccal
trocar instrumentation 2.7% (4.2% in CNFs and 0% for CBFs); and c) for
endoscopically assisted ORIF 4.2% (5% in CNFs, and 4% in CBFs). B) For low
submandibular approach 15.3% (26.1% for CNFs, 11.8% for CBFs, and 13.7% for
CNFs/CBFs). C) For the high submandibular/angular subparotid approach with
masseter transection 0% in CBFs. D) For the high submandibular/angular
transmassetric anteroparotid approach 0% (CNFs and CBFs). E) For the transparotid
retromandibular approach a) with nerve facial preparation 14.4% (23.9% in CNFs,
11.8% in CBFs and 13.7% for CNFs/CBFs); b) without facial nerve preparation 19%
(24.3% for CNFs and 10.5% for CBFs). F) For retromandibular transmassetric
anteroparotid approach 3.4% in CNFs/CBFs. G) For retromandibular transmassetric
anteroparotid approach with preauricular extension 2.3% for CNFs/CBFs. H) For
preauricular approach a) deep subfascial dissection plane 0% in CHFs b) for
subfascial approach using traditional preauricular incision 10% (8.5% in CHFs and
11.5% in CNFs). I) For retroauricular approach 3% for CHFs. PFNI rates reported
in the literature were as follows: A) for low submandibular approach 2.2%, B) for
retromandibular transparotid approach 1.4%; C) for preauricular approach 0.33%;
D) for high submandibular approach 0.3%; E) for deep retroparotid approach 1.5%.
CONCLUSION: According to published data for CHFs, a retroauricular approach or
deep subfascial preauricular approach was the safest to protect the facial nerve.
For CNFs, a transmassetric anteroparotid approach with retromandibular and
preauricular extension was the safest approach to decrease risk of FNI. For CBFs,
high submandibular incisions with either transmassetric anteroparotid approach
with retromandibular or transmassetric subparotid approach, followed by intraoral
(with or without endoscopic/transbuccal trocar) were the safest approaches with
respect to decreased risk of FNI.
PMID- 29339002
TI - Development of a new three-directional distractor system for the correction of
maxillary transverse and sagittal deficiency.
AB - PURPOSE: Class 3 malocclusions with maxillary deficiency, which are treated
surgically and/or ordonotically, are common among adult patients. The aim of this
study was to develop a three-directional bone-borne distractor that would allow
the transverse expansion and sagittal advancement of the maxilla simultaneously.
MATERIALS AND METHODS: Computed tomography images of a patient with maxillary
deficiency were transmitted to a software program, and a distractor was designed
with different sizes (D1, D2, D3) and manufactured from titanium alloy. Y-shape
segmental osteotomies were performed on the model, and vertical bite forces were
applied. The biomechanical properties were evaluated by using the finite element
method. RESULTS: The highest von Mises stress value on the body of the distractor
was seen in D2 (D2>D3>D1), with 234 N bite forces. D2 had maximum stress
distribution on maxillary bone under 234 N and 93 N (D2>D1>D3). No difference was
found among the plastic deformation rates according to biomechanical test
results. CONCLUSION: A three-directional bone-borne palatal distractor was
produced, and this distractor system can be used for the treatment of skeletal
class 3 patients with maxillary hypoplasia for its advantages of shortening the
overall treatment time and reducing the scar formation. However, further animal
and clinical studies are essential to determine the biological response of soft
and hard tissues.
PMID- 29339003
TI - Direct recovery of Bacillus subtilis xylanase from fermentation broth with an
alcohol/salt aqueous biphasic system.
AB - Xylanase enzyme degrades linear polysaccharide beta-1,4 xylan and the
hemicellulose of the plant cell wall. There is a growing demand in finding a cost
effective alternative for industrial scale production of xylanase with high
purity for pharmaceutical applications. In this study, an alcohol/salt aqueous
biphasic system (ABS) was adopted to recover xylanase from the Bacillus subtilis
fermentation broth. The effects of several ABS parameters such as types and
concentrations of alcohols and salts (i.e., sulphate, phosphate, and citrate),
amount of crude loading and pH of the system on the recovery of xylanase were
investigated. Partition coefficient of xylanase (KE), selectivity (S) and yield
(YT) of xylanase in top phase of the ABS were measured. Highest KE (6.58 +/-
0.05) and selectivity (4.84 +/- 0.33) were recorded in an ABS of pH 8 composed of
26% (w/w) 1-propanol, 18% (w/w) ammonium sulphate. High YT of 71.88% +/- 0.15 and
a purification fold (PFT) of 5.74 +/- 0.33 were recorded with this optimum
recovery of xylanase using alcohol/salt ABS. The purity of xylanase recovered was
then qualitatively verified with sodium dodecyl sulphate (SDS) gel
electrophoresis. The SDS profile revealed the purified xylanase was successfully
obtained in the top phase of the one-step 1-propanol/sulphate ABS with a distinct
single band.
PMID- 29339004
TI - Differential activation of brain areas in children with developmental
coordination disorder during tasks of manual dexterity: An ALE meta-analysis.
AB - Recent neuroimaging studies have reported atypical neural activation in children
with Developmental Coordination Disorder (DCD) during tasks assessing manual
dexterity. However, small sample sizes and subtle differences in task parameters
have led to inconsistent findings, rendering interpretation difficult. The aim of
the present meta-analysis was to quantitatively summarize this body of evidence
using activation likelihood estimation (ALE) analysis to identify reliable
regions of differential neural activation in children with DCD, compared to age
matched controls. Seven studies that adopted fMRI to compare children with and
without DCD during manual performance were identified following a literature
search. All were included in the ALE analysis. Compared to controls, children
with DCD showed reduced activation during a manual dexterity task in the middle
frontal gyrus, superior frontal gyrus, cerebellum, supramarginal gyrus, and
inferior parietal lobule. Children with DCD showed greater activation in parts of
the thalamus. Findings provide much needed clarification into the possible neural
contributors to atypical manual dexterity in DCD and highlight the need for
neuroimaging studies to include manual performance outcomes.
PMID- 29339005
TI - Effects of exercise and enrichment on behaviour in CD-1 mice.
AB - A host of scholarly work has characterized the positive effects of exercise and
environmental enrichment on behaviour and cognition in animal studies. The
purpose of this study was to investigate the uptake and longitudinal impact of
exercise and enrichment on the behavioural phenotype of male and female CD-1
mice. CD-1 mice housed in standard (STD) or exercise and enrichment (EE)
conditions post-weaning were tested in the 3-chamber sociability test, open
field, and elevated plus maze and exercise activity was monitored throughout the
enrichment protocol. Male and female EE mice both showed reduced anxiety and
activity in the open field and elevated plus maze relative to sex-matched STD
mice. EE altered social behaviours in a sex-specific fashion, with only female EE
mice showing increased social preference relative to female STD mice and a
preference for social novelty only present in male EE mice. This sexual
dimorphism was not observed to be a product of exercise uptake, as CD-1 mice of
both sexes demonstrated a consistent trend of wheel rotation frequencies. These
findings suggest the importance of considering variables such as sex and strain
on experimental design variables in future work on environmental enrichment.
PMID- 29339006
TI - Food allergy induces alteration in brain inflammatory status and cognitive
impairments.
AB - Accumulating evidence supports an increase in emotional and behavioral problems
in patients with food allergy, but the underlying mechanism remains poorly
understood. Here we found that in addition to inducing an increase of allergic
factors in serum, food allergy also increased levels of antigen-specific
immunoglobulins and mast cell marker in the brain. In particular, food allergy
increased the number of total microglia and the percentage of active microglia in
the cerebral cortex and hippocampal CA1 areas, and induced the increase of TNF
alpha in the cerebral cortex. Importantly, these brain allergic responses were
associated with behavioral impairments, including motor and learning deficits.
Taken together, our study provides some evidence for profound effects of food
allergy on brain functions, and thereby provides scientific basis for a better
explanation of emotional and behavioral problems among patients with food
allergy.
PMID- 29339007
TI - Suicides, homicides, accidents, and undetermined deaths in the U.S. military:
comparisons to the U.S. population and by military separation status.
AB - PURPOSE: To compare rates of external causes of mortality among individuals who
served in the military (before and after separation from the military) to the
U.S. POPULATION: METHODS: This retrospective cohort study examined all 3.9
million service members who served from 2002 to 2007. External cause mortality
data from 2002 to 2009 were used to calculate standardized mortality ratios.
Negative binomial regression compared differences in the mortality rates for pre-
and post-separation. RESULTS: Accident and suicide mortality rates were highest
among cohort members under 30 years of age, and most of the accident and suicide
rates for these younger individuals exceeded expectation given the U.S.
population mortality rates. Military suicide rates began below the expected U.S.
rate in 2002 but exceeded the U.S. rate by 2009. Accident, homicide, and
undetermined mortality rates remained below the U.S. rates throughout the study
period. Mortality rates for all external causes were significantly higher among
separated individuals compared with those who did not separate. Mortality rates
for individuals after separation from service decreased over time but remained
higher than the rates for those who had not separated from service. CONCLUSIONS:
Higher rates of death for all external causes of mortality after separation
suggest prevention opportunities. Future research should examine how
preseparation characteristics and experiences may predict postseparation adverse
outcomes to inform transition programs.
PMID- 29339008
TI - Updates on the molecular epidemiology of Enterovirus D68 after installation of
screening test among acute flaccid paralysis patients in Taiwan.
AB - In respond to acute flaccid paralysis (AFP) in association with Enterovirus D68
(EV-D68) infection, Taiwan Centers for Disease Control began to screen EV-D68
infection among each AFP patient since July 2015 and detected the first case in
August 2016. This article updated the molecular epidemiology trends of EV-D68
from the national surveillance data.
PMID- 29339009
TI - A boy with neck weakness.
PMID- 29339010
TI - Differences in Abortion Service Delivery in Hostile, Middle-ground, and
Supportive States in 2014.
AB - OBJECTIVES: In 2013, the majority of women lived in states considered hostile to
abortion rights, or states with numerous abortion restrictions. By comparison,
31% lived in supportive states. This study examined differences in abortion
service delivery according to the policy climate in which clinics must operate.
METHODS: Data come from the 2014 Abortion Provider Census, which contains
information about all known abortion-providing facilities in the United States.
In addition to number and type of facility, we examine several aspects of
abortion care: provision of only early medication abortion (EMA-only), whether an
advanced practice clinician provided abortions, gestational parameters, and
average charge for procedure. All indicators were examined nationally and
according to whether the clinic was in a state that was hostile, middle ground,
or supportive of abortion rights. RESULTS: In 2014, hostile and supportive states
accounted for the same proportion of all U.S. abortions-44% (each)-although 57%
of women age 15 to 44 lived in hostile states. Hostile states had one-half as
many abortion-providing facilities as supportive ones. EMA-only facilities
accounted for 37% of clinics in supportive states compared with 8% in hostile
states. Sixty-five percent of clinics in supportive states reported that advanced
practice clinicians provided abortion care, compared with 3% in hostile states.
After cost of living adjustments, a first-trimester surgical abortion was most
expensive in middle-ground states ($470) and least expensive in supportive states
($402). CONCLUSIONS: The distribution of abortion services, the type of facility
in which they are provided, and the amount a facility charges all vary according
to the abortion policy climate.
PMID- 29339011
TI - Facilitators and Barriers to Healthy Pregnancy Spacing among Medicaid
Beneficiaries: Findings from the National Strong Start Initiative.
AB - BACKGROUND: Closely spaced, unintended pregnancies are common among Medicaid
beneficiaries and create avoidable risks for women and infants, including preterm
birth. The Strong Start for Mothers and Newborns Initiative, a program of the
Center for Medicare and Medicaid Innovation, intended to prevent preterm birth
through psychosocially based enhanced prenatal care in maternity care homes,
group prenatal care, and birth centers. Comprehensive care offers the opportunity
for education and family planning to promote healthy pregnancy spacing. METHODS:
As of March 30, 2016, there were 42,138 women enrolled in Strong Start and 23,377
women had given birth. Individual-level data were collected through three
participant survey instruments and a medical chart review, and approximately one
half of women who had delivered (n = 10,374) had nonmissing responses on a
postpartum survey that asked about postpartum family planning. Qualitative case
studies were conducted annually for the first 3 years of the program and included
629 interviews with staff and 122 focus groups with 887 Strong Start
participants. RESULTS: Most programs tried to promote healthy pregnancy spacing
through family planning education and provision with some success. Group care
sites in particular established protocols for patient-centered family planning
education and decision making. Despite program efforts, however, barriers to
uptake remained. These included state and institutional policies, provider
knowledge and bias, lack of protocols for timing and content of education, and
participant issues such as transportation or cultural preferences. CONCLUSIONS:
The Strong Start initiative introduced a number of successful strategies for
increasing women's knowledge regarding healthy pregnancy spacing and access to
family planning. Multiple barriers can impact postpartum Medicaid participants'
capacity to plan and space pregnancies, and addressing such issues holistically
is an important strategy for facilitating healthy interpregnancy intervals.
PMID- 29339012
TI - Patient-Rated Access to Needed Care: Patient-Centered Medical Home Principles
Intertwined.
AB - BACKGROUND: Primary care teams can facilitate access to care by helping patients
to determine whether and when care is needed, and coordinating care across
multiple clinicians and settings. Appointment availability metrics may or may not
capture these contributions, but patients' own ratings of their access to care
provide an important alternative view of access that may be more closely related
to these key functions of care teams. PROCEDURES: We used a 2015 telephone survey
of 1,395 women veterans to examine associations between key care team functions
and patient-rated access to needed care. The care team functions were care
coordination, in-person communication (between patient and care team), and phone
communication (timely answers to health questions). We controlled for
sociodemographics, health status, care settings, and other experience of care
measures. KEY FINDINGS: Overall, 74% of participants reported always or usually
being able to see a provider for routine care, and 68% for urgent care. In
adjusted analyses, phone communication was associated with better ratings of
access to routine care (odds ratio [OR], 4.31; 95% CI, 2.65-6.98) and urgent care
(OR, 2.26; 95% CI, 1.23-4.18). Care coordination was also associated with better
ratings of access to routine care (OR, 1.66; 95% CI, 1.01-2.74) and urgent care
(OR, 2.26; 95% CI, 1.23-4.18). Associations with in-person communication were not
significant. CONCLUSIONS: Access, communication, and care coordination are
interrelated. Approaches to improving access may prove counterproductive if they
compromise the team's ability to coordinate care, or diminish the team's role as
a primary point of contact for patients.
PMID- 29339013
TI - The Use of Telemental Health to Meet the Mental Health Needs of Women Using
Department of Veterans Affairs Services.
AB - BACKGROUND: Women veterans are a growing segment of Department of Veterans
Affairs (VA) users with distinct mental health needs and well-documented barriers
to care. Telemental health holds much promise for reducing barriers to mental
health care. We assessed VA stakeholders' perceptions of telemental health's
appropriateness and potential to address the mental health needs of women veteran
VA users. METHODS: We conducted semistructured qualitative interviews with 40 key
leadership and clinical stakeholders at VA medical centers and associated
outpatient clinics. Transcripts were summarized in a template of key domains
developed based on the interview guide, and coded for topics relevant to women's
mental health needs and telehealth services. RESULTS: Telemental health was
perceived to increase access to mental health care, including same-gender care
and access to providers with specialized training, especially for rural women and
those with other limiting circumstances. Respondents saw women veterans as being
particularly poised to benefit from telemental health, owing to responsibilities
associated with childcare, spousal care, and elder caregiving. Interviewees
expressed enthusiasm for telemental health's potential and were eager to expand
services, including women-only mental health groups. Implementation challenges
were also noted. CONCLUSIONS: Overall, our stakeholders saw telemental health as
a good fit for helping to address the perceived needs of women veterans,
especially in addressing the geographical barriers experienced by rural women and
those with a limited ability to travel. These findings can help to inform gender
tailored expansion of telemental health within and outside of the VA.
PMID- 29339015
TI - Ambicor 2-Piece Inflatable Penile Prosthesis: Who and How?
AB - BACKGROUND: Currently the Ambicor is the only 2-piece inflatable penile
prosthesis (IPP) available in the United States. By eliminating the separate
reservoir, this provides certain advantages for patient and surgeon.
Nevertheless, it composes a small percentage of all IPPs implanted in the United
States. AIM: To detail the surgical technique for implantation, describe the
ideal patient candidates best suited for the Ambicor, and discuss the most common
and some rare complications with a review of the available published literature
in combination with our clinical experience. METHODS: A PubMed literature search
was performed to obtain all peer-reviewed articles published in English
specifically on the Ambicor 2-piece IPP. We also reviewed our clinical experience
with the Ambicor during the past 2 decades. RESULTS: The published data remain
limited, because few articles on the Ambicor have been published in the past 10
years. Overall complication rates were 2.1% to 9.5%. Patient satisfaction rates
were 75% to 96.4%, with similar partner satisfaction rates. Relative
contraindications for implantation include patients with significant penile
deformities, long narrow phalluses, or short phalluses. STRENGTHS AND
LIMITATIONS: Despite the limited available published data with short follow-up
periods, this review provides a comprehensive discussion on the technical aspects
and relevant perioperative counseling recommended for Ambicor implantation.
CONCLUSION: The prosthetic urologist should offer the Ambicor 2-piece IPP to
patients with erectile dysfunction whose non-surgical treatment has failed.
Certain implanters might want to avoid the blind retropubic reservoir placement
that occurs with 3-piece IPPs and might not be comfortable with an ectopic
approach and therefore prefer using a 2-piece device. We believe the ideal
Ambicor candidate is a patient with a current or future pelvic organ transplant,
decreased manual dexterity, in need of complete phallic reconstruction, or with
known extensive prior abdominopelvic surgery. Abdelsayed GA, Levine LA. Ambicor 2
Piece Inflatable Penile Prosthesis: Who and How? J Sex Med 2018;15:410-415.
PMID- 29339014
TI - Development of GPC3-Specific Chimeric Antigen Receptor-Engineered Natural Killer
Cells for the Treatment of Hepatocellular Carcinoma.
AB - Chimeric antigen receptor (CAR)-modified natural killer (NK) cells represent a
promising immunotherapeutic modality for cancer treatment. However, their
potential utilities have not been explored in hepatocellular carcinoma (HCC).
Glypian-3 (GPC3) is a rational immunotherapeutic target for HCC. In this study,
we developed GPC3-specific NK cells and explored their potential in the treatment
of HCC. The NK-92/9.28.z cell line was established by engineering NK-92, a highly
cytotoxic NK cell line with second-generation GPC3-specific CAR. Exposure of
GPC3+ HCC cells to this engineered cell line resulted in significant in vitro
cytotoxicity and cytokine production. In addition, soluble GPC3 and TGF-beta did
not significantly inhibit the cytotoxicity of NK-92/9.28.z cells in vitro, and no
significant difference in anti-tumor activities was observed in hypoxic (1%)
conditions. Potent anti-tumor activities of NK-92/9.28.z cells were observed in
multiple HCC xenografts with both high and low GPC3 expression, but not in those
without GPC3 expression. Obvious infiltration of NK-92/9.28.z cells, decreased
tumor proliferation, and increased tumor apoptosis were observed in the GPC3+ HCC
xenografts. Similarly, efficient retargeting on primary NK cells was achieved.
These results justified clinical translation of this GPC3-specific, NK cell-based
therapeutic as a novel treatment option for patients with GPC3+ HCC.
PMID- 29339016
TI - Expression of sperm PLCzeta and clinical outcomes of ICSI-AOA in men affected by
globozoospermia due to DPY19L2 deletion.
AB - Globozoospermia is characterized by the presence of 100% acrosomeless round
headed spermatozoa in an ejaculate. Failed fertilization after intracytoplasmic
sperm injection (ICSI) is commonly reported for globozoospermic couples and can
be overcome by artificial oocyte activation (AOA). Phospholipase C zeta (PLCzeta)
is one of the main sperm factors involved in oocyte activation and its low
expression levels mainly account for fertilization failure. Deletion of the
DPY19L2 gene is reported as a main genetic cause in over 70% of infertile men
with globozoospermia. The current study assesses the expression profile of sperm
PLCzeta at RNA and protein levels in 32 DPY19L2 deletion-mediated globozoospermic
men and reports corresponding clinical outcomes following ICSI with AOA. The
expression of PLCzeta relative to GAPDH at RNA (0.78 +/- 0.16 versus 1.65 +/-
0.24; P = 0.02) and protein (0.39 +/- 0.12 versus 0.83 +/- 0.13; P = 0.01) levels
in globozoospermic men with DPY19L2 deletion was significantly lower compared
with fertile men (n = 32). Fertilization rate in globozoospermic couples
following ICSI-AOA was significantly lower compared with fertile men (53.14 +/-
5.13% versus 87.64 +/- 2.38%, P < 0.001). However, implantation (26.2%) and
pregnancy (53.8%) rates were not jeopardized by DPY19L2 deletion in these
couples.
PMID- 29339017
TI - Reliability and agreement on embryo assessment: 5 years of an external quality
control programme.
AB - An external quality-control programme for morphology-based embryo quality
assessment, incorporating a standardized embryo grading scheme, was evaluated
over a period of 5 years to determine levels of inter-observer reliability and
agreement between practising clinical embryologists at IVF centres and the
opinions of a panel of experts. Following Guidelines for Reporting Reliability
and Agreement Studies, the Gwet index and proportion of positive (Ppos) and
negative agreement were calculated. For embryo morphology assessment, a
substantial degree of reliability was measured between the centres and the panel
of experts (Gwet index: 0.76; 95% CI 0.70 to 0.84). The agreement was higher for
good- versus poor-quality embryos. When multinucleation or vacuoles were
observed, low levels of reliability were obtained (Ppos: 0.56 and 0.43,
respectively). In blastocysts, the characteristic that presented the largest
discrepancy was that related to the inner cell mass. In decisions about the final
disposition of the embryo, reliability between centre and the panel of experts
was moderate (Gwet index: 0.51; 95% CI 0.41 to 0.60). In conclusion, the ability
of clinical embryologists to evaluate the presence of multinucleation and
vacuoles in the early cleavage embryo, and to determine the category of the inner
cell mass in blastocysts, needs to be improved.
PMID- 29339018
TI - Nicotine alleviates chronic stress-induced anxiety and depressive-like behavior
and hippocampal neuropathology via regulating autophagy signaling.
AB - Recently, we reported that chronic nicotine significantly improved chronic stress
induced impairments of cognition and the hippocampal synaptic plasticity in mice,
however, the underlying mechanism still needs to be explored. In the present
study, 32 male C57BL/6 mice were divided into four groups: control (CON), stress
(CUS), stress with chronic nicotine administration (CUS + Nic) and chronic
nicotine administration (Nic). The anxiety-like behavior and neuropathological
alteration of DG neurons were examined. Moreover, PC12 cells were examined with
corticosterone in the presence or absence of nicotine. Both cell viability and
apoptosis were determined. When treated simultaneously with an unpredictable
chronic mild stress (CUS), nicotine (0.2 mg/kg/d) attenuated behavioral deficits
and neuropathological alterations of DG neurons. Moreover, Western blotting
showed that chronic nicotine also elevated the level of autophagy makers
including Beclin-1 and LC3 II triggered by CUS. In addition, concomitant
treatment with nicotine (10 MUM) significantly attenuated the loss of PC12 cell
viability (p < .01) and apoptosis compared to that of corticosterone treatment
alone. Besides, chronic nicotine also enhanced the protein and RNA expression
levels of autophagy makers triggered by corticosterone, such as Beclin-1, LC3 II
and p62/SQSTM1. However, the above improvements were significantly blocked by
autophagy inhibitor 3-MA. Importantly, the activation of the PI3K/Akt/mTOR
signaling was carefully tested to illuminate the effects of chronic nicotine.
Consequently, chronic nicotine played a role of neuroprotection in either CUS
mice or corticosterone cells associating with the enhancement of the autophagy
signaling, which was involved in activating the PI3K/Akt/mTOR signaling.
PMID- 29339019
TI - Immuno-modulatory functions of the type-3 secretion system and impacts on the
pulmonary host defense: A role for ExoS of Pseudomonas aeruginosa in cystic
fibrosis.
AB - Number of previous reviews had described the structures and the various functions
of the exotoxins produced by the type-3 secretion system of Pseudomonas
aeruginosa and their roles in the interactions of this bacterium with host cells.
In this review, we summarize some relevant data of literature on ExoS, an
exotoxin from the type-3 secretion system of P. aeruginosa, with a particular
focus on the role of this toxin in the airways innate response of the host to
infection by this bacterium, and its implication in the elimination of
Staphylococcus aureus from the airways of patients with cystic fibrosis.
PMID- 29339021
TI - Being Andrew Lees.
PMID- 29339020
TI - Cecile Vogt.
PMID- 29339022
TI - Exposure assessments for a cross-sectional epidemiologic study of US carbon
nanotube and nanofiber workers.
AB - BACKGROUND: Recent animal studies have suggested the potential for wide-ranging
health effects resulting from exposure to carbon nanotubes and nanofibers
(CNT/F). To date, no studies in the US have directly examined the relationship
between occupational exposure and potential human health effects. OBJECTIVES: Our
goal was to measure CNT/F exposures among US workers with representative job
types, from non-exposed to highly exposed, for an epidemiologic study relating
exposure to early biologic effects. METHODS: 108 participants were enrolled from
12 facilities across the US. Personal, full-shift exposures were assessed based
on the mass of elemental carbon (EC) at the respirable and inhalable aerosol
particle size fractions, along with quantitatively characterizing CNT/F and
estimating particle size via transmission electron microscopy (TEM).
Additionally, sputum and dermal samples were collected and analyzed to determine
internal exposures and exposures to the hands/wrists. RESULTS: The mean exposure
to EC was 1.00 MUg/m3 at the respirable size fraction and 6.22 MUg/m3 at the
inhalable fraction. Analysis by TEM found a mean exposure of 0.1275 CNT/F
structures/cm3, generally to agglomerated materials between 2 and 10 MUm.
Internal exposures to CNT/F via sputum analysis were confirmed in 18% of
participants while ~70% had positive dermal exposures. CONCLUSIONS: We
demonstrated the occurrence of a broad range of exposures to CNT/F within 12
facilities across the US. Analysis of collected sputum indicated internal
exposures are currently occurring within the workplace. This is an important
first step in determining if exposures in the workforce have any acute or lasting
health effects.
PMID- 29339023
TI - Calculated shape dependence of electromagnetic field in tip-enhanced Raman
scattering by using a monopole antenna model.
AB - To evaluate the shape of an Ag tip with regard to tip-enhanced Raman scattering
(TERS) signal, the enhanced electromagnetic (EM) field and scattering spectrum,
arising from surface plasmon resonance at the apex of the tip, were calculated
using a finite-difference time domain (FDTD) method. In the calculated forward
scattering spectra from the smooth Ag tip, the band appeared within the visible
region, similar to the experimental results and calculation for a corrugated Ag
cone. In the FDTD calculation of TERS, the Ag tip acting as a monopole antenna
was adopted by insertion of a perfect electric conductor between the root of the
tip and a top boundary surface of the calculation space. As a result, the EM
field was only enhanced at the apex. The shape dependence i.e. the EM field
calculated at the apex with various curvatures on the different tapered tips,
obtained using the monopole antenna model, was different from that simulated
using a conventional dipole antenna model.
PMID- 29339025
TI - Electroacoustic verification of frequency modulation systems in cochlear implant
users.
AB - INTRODUCTION: The frequency modulation system is a device that helps to improve
speech perception in noise and is considered the most beneficial approach to
improve speech recognition in noise in cochlear implant users. According to
guidelines, there is a need to perform a check before fitting the frequency
modulation system. Although there are recommendations regarding the behavioral
tests that should be performed at the fitting of the frequency modulation system
to cochlear implant users, there are no published recommendations regarding the
electroacoustic test that should be performed. OBJECTIVE: Perform and determine
the validity of an electroacoustic verification test for frequency modulation
systems coupled to different cochlear implant speech processors. METHODS: The
sample included 40 participants between 5 and 18 year's users of four different
models of speech processors. For the electroacoustic evaluation, we used the
Audioscan Verifit device with the HA-1 coupler and the listening check devices
corresponding to each speech processor model. In cases where the transparency was
not achieved, a modification was made in the frequency modulation gain adjustment
and we used the Brazilian version of the "Phrases in Noise Test" to evaluate the
speech perception in competitive noise. RESULTS: It was observed that there was
transparency between the frequency modulation system and the cochlear implant in
85% of the participants evaluated. After adjusting the gain of the frequency
modulation receiver in the other participants, the devices showed transparency
when the electroacoustic verification test was repeated. It was also observed
that patients demonstrated better performance in speech perception in noise after
a new adjustment, that is, in these cases; the electroacoustic transparency
caused behavioral transparency. CONCLUSION: The electroacoustic evaluation
protocol suggested was effective in evaluation of transparency between the
frequency modulation system and the cochlear implant. Performing the adjustment
of the speech processor and the frequency modulation system gain are essential
when fitting this device.
PMID- 29339024
TI - Nrf2/ARE pathway attenuates oxidative and apoptotic response in human
osteoarthritis chondrocytes by activating ERK1/2/ELK1-P70S6K-P90RSK signaling
axis.
AB - Nrf2, a redox regulated transcription factor, has recently been shown to play a
role in cartilage integrity but the mechanism remains largely unknown.
Osteoarthritis (OA) is a multifactorial disease in which focal degradation of
cartilage occurs. Here, we studied whether Nrf2 exerts chondroprotective effects
by suppressing the oxidative stress and apoptosis in IL-1beta stimulated human OA
chondrocytes. Expression of Nrf2 and its target genes HO-1, NQO1 and SOD2 was
significantly high in OA cartilage compared to normal cartilage and was also
higher in damaged area compared to smooth area of OA cartilage of the same
patient. Human chondrocytes treated with IL-1beta resulted in robust Nrf2/ARE
reporter activity, which was inhibited by pretreatment with antioxidants
indicating that Nrf2 activity was due to IL-1beta-induced ROS generation. Ectopic
expression of Nrf2 significantly suppressed the IL-1beta-induced generation of
ROS while Nrf2 knockdown significantly increased the basal as well as IL-1beta
induced ROS levels in OA chondrocytes. Further, Nrf2 activation significantly
inhibited the IL-1beta-induced activation of extrinsic and intrinsic apoptotic
pathways as determined by inhibition of DNA fragmentation, activation of Caspase
3,-8,-9, cleavage of PARP, release of cytochrome-c, suppression of mitochondrial
dysfunction and mitochondrial ROS production in OA chondrocytes. Nrf2 over
expression in OA chondrocytes increased the expression of anti-apoptotic proteins
while pro-apoptotic proteins were suppressed. Importantly, Nrf2 over-expression
activated ERK1/2 and its downstream targets-ELK1, P70S6K and P90RSK and
suppressed the IL-1beta-induced apoptosis whereas inhibition of ERK1/2 activation
abrogated the protective effects of Nrf2 in OA chondrocytes. Taken together, our
data demonstrate that Nrf2 is a stress response protein in OA chondrocytes with
anti-oxidative and anti-apoptotic function and acts via activation of ERK1/2/ELK1
P70S6K-P90RSK signaling axis. These activities of Nrf2 make it a promising
candidate for the development of novel therapies for the management of OA.
PMID- 29339027
TI - A comparative study of osteopontin and MMP-2 protein expression in peripheral and
central giant cell granuloma of the jaws.
AB - INTRODUCTION: Oral peripheral and central giant cell granulomas are lesions with
little-known etiology and pathogenesis. OBJECTIVE: The aim of this study was to
compare matrix metalloproteinases-2 and osteopontin protein expression in the
multinucleated giant cells and mononuclear cells of the peripheral and central
giant cell granuloma lesions. METHODS: In this retrospective study, the presence
of matrix metalloproteinases-2 and osteopontin in 37 cases of central giant cell
granuloma and 37 cases of peripheral giant cell granuloma paraffin blocks were
assessed by streptavidin-biotin immunohistochemistry. Independent sample t-test,
Chi-square, Mann-Whitney tests and Spearman's rank correlation coefficient were
used. RESULTS: The osteopontin was expressed in both multinucleated giant cells
and mononuclear cells in all cases of peripheral and central giant cells
granulomas. However, the matrix metalloproteinases-2 expression was positive in
86.5% of giant cells and it was positive in all of mononuclear cells in
peripheral giant cells granuloma. In central giant cells granulomas, 91.8% of
giant cells and all mononuclear cells were positive for matrix metalloproteinases
2 marker. Percentage and Intensity of staining were significantly higher in
central than peripheral giant cells lesions, for both markers (p?0.05).
CONCLUSION: This study showed that the expression of osteopontin in giant cells
supports the theory of osteolcastic nature of these cells. Also, the presence of
osteopontin and matrix metalloproteinases-2 in mononuclear cells may indicate the
monocyte-macrophage origin of these cells, as the differentiation of the
precursors of the mononuclear stromal monocyte/macrophage to osteoclasts is
possibly affected by the expression of osteolytic factors. Also, may be
differences in biological behaviors of these lesions are associated with the
level of osteopontin and matrix metalloproteinases-2 expression.
PMID- 29339028
TI - Overexpression of CDC7 in malignant salivary gland tumors correlates with tumor
differentiation.
AB - INTRODUCTION: Cell division cycle-7 protein is a serine/threonine kinase that has
a basic role in cell cycle regulation and is a potential prognostic or
therapeutic target in some human cancers. OBJECTIVES: This study investigated the
expression of cell division cycle-7 protein in benign and malignant salivary
gland tumors and also its correlation with clinicopathologic factors. METHODS:
Immunohistochemical expression of cell division cycle-7 was evaluated in 46
cases, including 15 adenoid cystic carcinoma, 12 mucoepidermoid carcinoma, 14
pleomorphic adenoma, and 5 normal salivary glands. Cell division cycle-7
expression rate and intensity were compared statistically. RESULTS: The protein
was expressed in almost all tumors. The intensity and mean of cell division cycle
7 expression were higher in malignant tumors in comparison with pleomorphic
adenomas (p=0.000). The protein expression was correlated with tumor grades
(p=0.000). CONCLUSIONS: The present study demonstrated cell division cycle-7
overexpression in malignant salivary gland tumors in comparison with pleomorphic
adenomas, and also a correlation with tumor differentiation. Therefore, this
protein might be a potential prognostic and therapeutic target for salivary gland
tumors.
PMID- 29339026
TI - Tinnitus and sound intolerance: evidence and experience of a Brazilian group.
AB - INTRODUCTION: Tinnitus and sound intolerance are frequent and subjective
complaints that may have an impact on a patient's quality of life. OBJECTIVE: To
present a review of the salient points including concepts, pathophysiology,
diagnosis and approach of the patient with tinnitus and sensitivity to sounds.
METHODS: Literature review with bibliographic survey in LILACS, SciELO, Pubmed
and MEDLINE database. Articles and book chapters on tinnitus and sound
sensitivity were selected. The several topics were discussed by a group of
Brazilian professionals and the conclusions were described. RESULTS: The
prevalence of tinnitus has increased over the years, often associated with
hearing loss, metabolic factors and inadequate diet. Medical evaluation should be
performed carefully to guide the request of subsidiary exams. Currently available
treatments range from medications to the use of sounds with specific
characteristics and meditation techniques, with variable results. CONCLUSION: A
review on tinnitus and auditory sensitivity was presented, allowing the reader a
broad view of the approach to these patients, based on scientific evidence and
national experience.
PMID- 29339029
TI - Degree of tinnitus improvement with stapes surgery - a review.
AB - INTRODUCTION: Otospongiosis is temporal bone osteodystrophy, characterized by
disordered bone resorption and neoformation in genetically predisposed
individuals. Clinically, otospongiosis is characterized by progressive conductive
and/or mixed hearing loss and by tinnitus. OBJECTIVE: A review of the last two
decades of publications that report the degree of tinnitus improvement with
stapes surgery. METHODS: 125 articles published in the last 20 years mentioning
the relationship between otosclerosis and tinnitus. Literature has always shown
that the hearing improvement after stapes surgery was the main result sought and
found. However, recent articles has reinforced the need for surgery for the
tinnitus improvement. The ideal time to assess tinnitus through different scales
is in the sixth month post-operative. The estimated average hearing improvement
is 93% and tinnitus is 85.52%. RESULTS: Summaries of 12 articles were reviewed
which fulfilled the search criteria of the survey, and 8 studies were included in
the study according the selection criteria. This studies investigating the degree
of tinnitus improvement with stapes surgery, using different scales as: tinnitus
functional index, visual analog scale, tinnitus functional index and visual
analog scale, visual analog scale and "questionnaire asking about tinnitus",
Newman's method and Tinnitus Score Advocated by the Japan Audiological Society.
The total of the samples of the evaluated articles was of 254 participants.
CONCLUSION: We conclude that stapes surgery is effective for the treatment of
tinnitus (average improvement is 85.52%), and hearing loss (average improvement
is 93%). When deciding about the surgical indication in patients with
otosclerosis, the presence and level tinnitus should be considered as well as the
level of hearing.
PMID- 29339030
TI - Preoperative insulin therapy as a marker for type 2 diabetes remission in obese
patients after bariatric surgery.
AB - BACKGROUND: Obesity not only increases the chances of developing diabetes-one of
the top causes of death in the United States-but it also results in further
medical complications. OBJECTIVE: To compare the 6-month and 1-year postoperative
remission rates of type 2 diabetic (T2D) patients after bariatric surgery based
on preoperative glycosylated hemoglobin (A1C) stratification and pharmacologic
therapy: insulin-dependent diabetic (IDD) versus noninsulin-dependent diabetic
(NIDD). SETTING: Academic hospital, United States. METHODS: We retrospectively
analyzed a prospectively maintained database of 186 obese patients with a
diagnosis T2D who had undergone either a sleeve gastrectomy or a Roux-en-Y
gastric bypass surgery at our hospital. RESULTS: At 6 months (n = 180), patients
who were stratified by preoperative A1C levels (<6.5; >=6.5 to<8; >=8) had 70.5%,
51.7%, and 30.0% remission rates (P<.001) and at 1 year (n = 118) patients had
72.0%, 54.0%, and 42.8% remission rates (P = .053), respectively. When patients
were substratified by preoperative pharmacologic therapy, IDD and NIDD patients
had different remission rates within the same A1C level. At 6-months follow-up
within A1C >=6.5 to<8 (IDD versus NIDD), the remission rate was 23.5% versus
64.1% (odds ratio [OR]: .173, confidence interval [CI]: .0471, .6308, P = .0079),
and within A1C >=8 the remission was 24.0% versus 37.5% (OR: .5263, CI: .2115,
1.3096, P = .1676), respectively. At 1-year follow-up within A1C >=6.5 to<8, the
remission rate was 30.0% versus 62.9% (OR: .2521, CI: .0529, 1.2019, P = .0838),
and within A1C >=8 the remission was 31.4% versus 61.9% (OR: .2821, CI: .0908,
.8762, P = .0286), respectively. Furthermore, when IDD patients were compared
between A1C >=6.5 to<8 and A1C >=8 the remission rates were nearly identical, and
for NIDD patients A1C was not significantly associated with remission regardless
of the level, except at 6 months. CONCLUSION: While a difference was observed
between overall A1C levels-the lower the A1C level, the higher the remission rate
IDD patients had lower remission rates than NIDD patients irrespective of A1C
levels; further, IDD patients performed similarly across A1C levels.
PMID- 29339031
TI - Resolution of type 2 diabetes after sleeve gastrectomy: a 2-step hypothesis.
AB - BACKGROUND: Weight loss (WL) and altered gut hormonal levels are involved in
glucose homeostasis after laparoscopic sleeve gastrectomy (LSG). OBJECTIVES: The
aim of this study was to evaluate the time-related effects of WL, ghrelin, and
glucacon-like peptide-1 (GLP-1) plasma concentrations on type 2 diabetes
resolution after LSG. SETTING: University hospital, Italy. METHODS: Ninety-one
patients who underwent LSG were investigated. Insulin secretion (insulinogenic
index [IGI]), insulin resistance, plasma glucose level and percentage glycated
hemoglobin using the oral glucose tolerance test were assessed before surgery, on
postoperative day 3, and then at 6, 12, 24, and 36 months after LSG. At the same
time points, WL, ghrelin, and GLP-1 levels were determined. RESULTS: During
follow-up, the resolution rate of type 2 diabetes was 9.4%, 42.3%, 71.8%, 81.2%,
and 91.8%, respectively. Ghrelin plasma concentrations decreased significantly
after LSG (271.5 +/- 24.5 pg/mL versus 122.4 +/- 23.4 pg/mL, P = .04). GLP-1
plasma concentrations increased significantly after LSG (1.7 +/- 2.6 pg/mL versus
2.5 +/- 3.4 pg/mL, P = .04). The percentage of excess weight loss and IGI
presented a positive linear correlation (r) at all follow-up time points with a
strong positive correlation at 12 and 24 months. A strong negative correlation
between ghrelin and IGI was recorded during the first 3 days after LSG (r = -.9).
GLP-1 and IGI presented a strong positive correlation at day 3 and 6 months
(i.e., .8 and .8, respectively). CONCLUSION: LSG may affect glucose homeostasis
by 2 different time-related modes: a first step in which the hormonal changes
play a predominant role in glucose homeostasis and a second step in which the
percentage excess weight loss determines the metabolic results.
PMID- 29339032
TI - The relation between pro-oxidant antioxidant balance and glycolipid profile, 6
months after gastric bypass surgery.
AB - BACKGROUND: Morbid obesity is a chronic disease that contributes to increased
oxidative stress. Gastric bypass surgery is the gold standard method in treating
co-morbidities. OBJECTIVES: The objective of this study was to evaluate the
relation between pro-oxidant antioxidant balance (PAB) as one measure of
oxidative stress and glycolipid profile 6 months after gastric bypass surgery.
SETTING: Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad,
Iran. METHODS: Thirty-five morbidly obese patients with body mass index >=35
kg/m2 with co-morbidities or <=40 kg/m2 were randomly recruited. The PAB assay
was used to estimate oxidative stress. Anthropometrics and glycolipid profile
were collected at recruitment and 6 months after surgery. Statistical analysis
was performed using SPSS 16 software. RESULTS: The study showed a significant
postoperative reduction in serum PAB values compared with the baseline (P<.001).
All anthropometric and several glycolipid parameters significantly reduced after
surgery (P<.001), while serum high-density lipoprotein cholesterol was
unaffected. Repeated measures analysis of variance showed that postoperative PAB
values were affected by gastric bypass surgery (F = 12.51, P = .001). Regression
analysis demonstrated medication usage controlling co-morbidities (beta^ = -.6, P
= .002) and fasting blood glucose (beta^ = .41, P = .04) as independent factors
in predicting PAB values 6 months after surgery. CONCLUSIONS: Gastric bypass
surgery can reduce PAB values in favor of antioxidants 6 months after the
operation. Accordingly, fasting blood glucose after gastric bypass surgery can be
an independent factor in predicting PAB values.
PMID- 29339033
TI - Helminth Modulation of Lung Inflammation.
AB - Parasitic helminths must establish chronic infections to complete their life
cycle and therefore are potent modulators of multiple facets of host physiology.
Parasitic helminths have coevolved with humans to become arguably master
selectors of our immune system, whereby they have impacted on the selection of
genes with beneficial mutations for both host and parasite. While helminth
infections of humans are a significant health burden, studies have shown that
helminths or helminth products can alter susceptibility to unrelated infectious
or inflammatory diseases. This has generated interest in the use of helminth
infections or molecules as therapeutics. In this review, we focus on the impact
of helminth infections on pulmonary immunity, especially with regard to
homeostatic lung function, pulmonary viral and bacterial (co)infections, and
asthma.
PMID- 29339034
TI - Extracellular matrix proteins and carcinoembryonic antigen-related cell adhesion
molecules characterize pancreatic duct fluid exosomes in patients with pancreatic
cancer.
AB - BACKGROUND: Exosomes are nanovesicles that have been shown to mediate
carcinogenesis in pancreatic ductal adenocarcinoma (PDAC). Given the direct
communication of pancreatic duct fluid with the tumor and its relative
accessibility, we aimed to determine the feasibility of isolating and
characterizing exosomes from pancreatic duct fluid. METHODS: Pancreatic duct
fluid was collected from 26 patients with PDAC (n = 13), intraductal papillary
mucinous neoplasm (IPMN) (n = 8) and other benign pancreatic diseases (n = 5) at
resection. Exosomes were isolated by serial ultracentrifugation, proteins were
identified by mass spectrometry, and their expression was evaluated by
immunohistochemistry. RESULTS: Exosomes were isolated from all specimens with a
mean concentration of 5.9 +/- 1 * 108 particles/mL and most frequent size of 138
+/- 9 nm. Among the top 35 proteins that were significantly associated with PDAC,
multiple carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) and
extracellular matrix (ECM) proteins were identified. Interestingly, CEACAM 1/5
expression by immunohistochemistry was seen only on tumor epithelia whereas
tenascin C positivity was restricted to stroma, suggesting that both tumor and
stromal cells contributed to exosomes. CONCLUSION: This is the first study
showing that exosome isolation is feasible from pancreatic duct fluid, and that
exosomal proteins may be utilized to diagnose patients with PDAC.
PMID- 29339035
TI - The effect of dietary carbohydrate on gastroesophageal reflux disease.
AB - BACKGROUND: Acid changes in gastroesophageal reflux with vary component in the
food have less been studied, especially carbohydrate. We plan to clarify the
effect of different carbohydrate density on low esophageal acid and reflux
symptoms of patients with gastroesophgeal reflux disease. METHODS: Twelve
patients (52 +/- 12 years old; five female) with gastroesophageal reflux disease
were recruited for the prospective crossover study. Each patient was invited for
panendoscope, manometry and 24 h pH monitor. The two formulated liquid meal, test
meal A: 500 ml liquid meal (containing 84.8 g carbohydrate) and B: same volume
liquid meal (but 178.8 g carbohydrate) were randomized supplied as lunch or
dinner. Reflux symptoms were recorded. RESULTS: There are significant statistic
differences in more Johnson-DeMeester score (p = 0.019), total reflux time (%) (p
= 0.028), number of reflux periods (p = 0.026) and longest reflux (p = 0.015)
after high carbohydrate diet than low carbohydrate. Total reflux time and number
of long reflux periods more than 5 min are significant more after high
carbohydrate diet. CONCLUSION: More acid reflux symptoms are found after high
carbohydrate diet. High carbohydrate diet could induce more acid reflux in low
esophagus and more reflux symptoms in patients with gastroesophageal reflux
disease.
PMID- 29339036
TI - A cone-beam computed tomography study of C-shaped root canal systems in
mandibular second premolars in a Taiwan Chinese subpopulation.
AB - BACKGROUND/PURPOSE: The purpose of this study is to investigate the prevalence
and the morphologic characteristics of the radicular groove and root canal system
in human mandibular second premolars with C-shaped root in a Taiwan Chinese
subpopulation using cone-beam computed tomographic (CBCT) imaging. METHODS: CBCT
images of 580 mandibular second premolars were collected from 317 patients. All
of the mandibular second premolars were examined in serial axial sections to
identify the presence of any C-shaped root and C-shaped canal systems. The
morphologic characteristics of mandibular second premolars with C-shaped roots
were studied by performing measurements of serial axial sections. RESULTS: The
prevalence rate of mandibular second premolars with a C-shaped root was 3.45%
(20/580 teeth) and the rate of those with a C-shaped canal system was 2.24%
(13/580 teeth). It was found that 69% of the radicular grooves were located on
the lingual half of the root (9/13 teeth) in mandibular second premolars with a C
shaped canal system. In those teeth with a lingual radicular groove, the main
canal was toward the buccal side. Frequently, the first C-shaped canal image was
found at the mid-root level. The deepest part of the radicular groove was located
at about 2.5 mm apical to the first C-shaped canal image. CONCLUSION: There was a
2-3% morphologic variation of the mandibular second premolar with a C-shaped root
canal system among the Taiwan Chinese subpopulation investigated in this study.
Detailed knowledge of the morphological characteristics of teeth may be valuable
when choosing clinical treatments.
PMID- 29339037
TI - Reply to the letters to the editor regarding the elevated body mass index is a
risk factor associated with possible liver cirrhosis across different etiologies
of chronic liver disease: Methodological issues.
PMID- 29339038
TI - Curcumin inhibits TGF-beta1-induced connective tissue growth factor expression
through the interruption of Smad2 signaling in human gingival fibroblasts.
AB - BACKGROUND/PURPOSE: Many fibrotic processes are associated with an increased
level of transforming growth factor-beta1 (TGF-beta1). TGF-beta1 can increase
synthesis of matrix proteins and enhance secretion of protease inhibitors,
resulting in matrix accumulation. Connective tissue growth factor (CTGF) is a
downstream profibrotic effector of TGF-beta1 and is associated with the fibrosis
in several human organs. Curcumin has been applied to reduce matrix accumulation
in fibrotic diseases. This study was aimed to evaluate whether curcumin could
suppress TGF-beta1-induced CTGF expression and its related signaling pathway
involving in this inhibitory action in primary human gingival fibroblasts.
METHODS: The differences in CTGF expression among three types of gingival
overgrowth and normal gingival tissues were assessed by immunohistochemistry.
Gingival fibroblast viability in cultured media with different concentrations of
curcumin was studied by MTT assay. The effect of curcumin on TGF-beta1-induced
CTGF expression in primary human gingival fibroblasts was examined by
immunoblotting. Moreover, the proteins involved in TGF-beta1 signaling pathways
including TGF-beta1 receptors and Smad2 were also analyzed by immunoblotting.
RESULTS: CTGF was highly expressed in fibroblasts, epithelial cells and some of
endothelial cells, smooth muscle cells, and inflammatory cells in phenytoin
induced gingival overgrowth tissues rather than in those of hereditary and
inflammatory gingival overgrowth tissues. Moreover, CTGF expression in the
epithelial and connective tissue layers was higher in phenytoin-induced gingival
overgrowth tissues than in normal gingival tissues. Curcumin was nontoxic and
could reduce TGF-beta1-induced CTGF expression by attenuating the phosphorylation
and nuclear translocation of Smad2. CONCLUSION: Curcumin can suppress TGF-beta1
induced CTGF expression through the interruption of Smad2 signaling.
PMID- 29339039
TI - Sixty years of DNA melting in review: Comment on the review article "DNA melting
and energetics of the double helix" by Alexander Vologodskii and Maxim D. Frank
Kamenetskii.
PMID- 29339040
TI - Effectiveness of workplace diabetes prevention programs: A systematic review of
the evidence.
AB - PURPOSE: The primary purpose is to review diabetes workplace interventions and
the degree to which they improve diabetes-related outcomes in employees diagnosed
with or at risk for T2DM. METHODS: Three electronic databases and ancestry
searches were used to identify peer reviewed articles published in English from
2000 to June 2017. RESULTS: The number of participants represented by the 22
selected studies, excluding one large outlier, was 4243. On average, the samples
were 57% female and ethnically diverse. Interventions-healthy eating behaviors,
physical activity, and/or monitoring and self-managing diabetes and
cardiovascular risk factors-were delivered in group sessions of fewer than 20
employees. Programs involved 1-h weekly sessions held during lunch hour or at
other times during the workday for 12 to 24 weeks. Study outcomes, commonly
measured at 6 and/or 12 months, were consistently positive. CONCLUSION: The
literature search uncovered beginning evidence that workplace interventions hold
promise for preventing diabetes and/or its complications. More rigorous,
creatively designed, workplace studies, are needed for employees at high-risk for
developing diabetes. PRACTICE IMPLICATIONS: Implications include the need for
employer education about the benefits of employer support for such programs and
attention to motivational strategies so employees will take full advantage of
programs that are offered.
PMID- 29339042
TI - Chemotherapy-induced Nausea and Vomiting Prophylaxis in High-dose Melphalan and
Autologous Stem Cell Transplantation.
PMID- 29339041
TI - Factors influencing women's perceptions of shared decision making during labor
and delivery: Results from a large-scale cohort study of first childbirth.
AB - OBJECTIVE: To examine correlates of shared decision making during labor and
delivery. METHODS: Data were from a cohort of women who gave birth to their first
baby in Pennsylvania, 2009-2011 (N = 3006). We used logistic regression models to
examine the association between labor induction and mode of delivery in relation
to women's perceptions of shared decision making, and to investigate
race/ethnicity and SES as potential moderators. RESULTS: Women who were Black and
who did not have a college degree or private insurance were less likely to report
high shared decision making, as well as women who underwent labor induction,
instrumental vaginal or cesarean delivery. Models with interaction terms showed
that the reduction in odds of shared decision making associated with cesarean
delivery was greater for Black women than for White women. CONCLUSIONS: Women in
marginalized social groups were less likely to report shared decision making
during birth and Black women who delivered by cesarean had particularly low odds
of shared decision making. PRACTICE IMPLICATIONS: Strategies designed to improve
the quality of patient-provider communication, information sharing, and shared
decision making must be attentive to the needs of vulnerable groups to ensure
that such interventions reduce rather than widen disparities.
PMID- 29339043
TI - The Relationship Between Red Cell Distribution Width and Cancer-Specific Survival
in Patients With Renal Cell Carcinoma Treated With Partial and Radical
Nephrectomy.
AB - INTRODUCTION: The aim of the study was to evaluate the influence of red cell
distribution width (RDW) on cancer-specific survival (CSS) in patients who
undergo nephrectomy for renal cell carcinoma (RCC). PATIENTS AND METHODS: A total
number of 434 patients with pathologically proven RCC treated with radical or
partial nephrectomy between 2003 and 2012 were identified in a single tertiary
academic center. To evaluate the accuracy of RDW for CSS prediction, a receiver
operating characteristic (ROC) curve was plotted. Patients were divided into 2
groups, with low and high RDW, according to the optimal cutoff value, which was
determined according to the ROC curve. The association between groups and CSS was
analyzed using the Kaplan-Meier method with log-rank testing. The Cox
proportional hazards regression model was applied to perform univariate and
multivariate analysis for CSS. RESULTS: Median follow-up was 2146 days. There
were no differences between subjects with high and low RDW in terms of sex, age,
body mass index, histological type of tumor, frequency of partial nephrectomy,
and TNM stage. Patients with high RDW had significantly lower hematocrit,
hemoglobin level, and red blood cell count. Tumor necrosis and larger tumor size
were significantly more prevalent in the group of patients with high RDW. CSS was
significantly lower in patients with RDW >= 13.9% compared with patients with RDW
< 13.9%. After adjustment for pathological and clinical covariates RDW remained
an independent predictor for CSS in a multivariable model for CSS. CONCLUSION:
Our study revealed that the RDW might be an easily obtainable prognostic marker
in RCC patients treated with nephrectomy.
PMID- 29339044
TI - The Cardiovascular Toxicity of Abiraterone and Enzalutamide in Prostate Cancer.
AB - INTRODUCTION: The cardiovascular toxicity related to abiraterone and enzalutamide
has been previously studied by our group. In this analysis, we aim to update our
previous findings related to abiraterone and enzalutamide, including the new
available evidence, both in castration-resistant and hormone-sensitive prostate
cancer. PATIENTS AND METHODS: Prospective studies were identified by searching
the MEDLINE/PubMed, Cochrane Library, and ASCO Meeting abstracts. Combined
relative risks (RRs) and 95% confidence intervals (CIs) were calculated using
fixed- or random-effects methods. RESULTS: We included 7 articles in this meta
analysis, covering a total of 8660 patients who were used to evaluate
cardiovascular toxicity. The use of new hormonal agents was associated with an
increased risk of all-grade (RR, 1.36; 95% CI, 1.13-1.64; P = .001) and high
grade (RR, 1.84; 95% CI, 1.21-2.80; P = .004) cardiac toxicity. The use of new
hormonal agents was also associated with an increased risk of all-grade (RR,
1.98; 95% CI, 1.62-2.43; P = .001) and high-grade (RR, 2.26; 95% CI, 1.84-2.77; P
= .004) hypertension compared with the controls. Abiraterone was found to
significantly increase the risk of both cardiac toxicity and hypertension,
whereas enzalutamide significantly increases only the risk of hypertension. No
differences were found based on the dose of prednisone used with abiraterone. The
major limitation of this study is that data are available only as aggregate, and
no single-patient information could be analyzed. CONCLUSIONS: Abiraterone and
enzalutamide significantly increase the incidence and RR of cardiovascular
toxicity in patients affected by metastatic prostate cancer. Follow-up for the
onset of treatment-related cardiovascular events should therefore be considered
in these patients.
PMID- 29339045
TI - Deficiency of dietary pyridoxine disturbed the intestinal physical barrier
function of young grass carp (Ctenopharyngodon idella).
AB - The aim of this study was to assess the effects of dietary pyridoxine (PN)
deficiency on intestinal antioxidant capacity, cell apoptosis and intercellular
tight junction in young grass carp (Ctenopharyngodon idella). A total of 540
young grass carp (231.85 +/- 0.63 g) were fed six diets containing graded levels
of PN (0.12-7.48 mg/kg diet) for 10 weeks. At the end of the feeding trial, the
fish were challenged with Aeromonas hydrophila for 2 weeks. The results showed
that compared with the optimal PN level, PN deficiency (1) increased the contents
of reactive oxygen species (ROS), malondialdehyde (MDA) and protein carbonyl
(PC), decreased the activities and mRNA levels of antioxidant enzymes such as
copper, zinc superoxide dismutase (CuZnSOD), catalase (CAT), glutathione
peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR)
(P < .05); (2) up-regulated the mRNA levels of cysteinyl aspartic acid-protease-3
(caspase-3), caspase-7, caspase-8, caspase-9, Bcl-2 associated X protein (Bax),
apoptotic protease activating factor-1 (Apaf-1) and Fas ligand (FasL), and down
regulated the mRNA levels of inhibitor of apoptosis proteins (IAP), B-cell
lymphoma protein-2 (Bcl-2) and myeloid cell leukaemia-1 (Mcl-1) (P < .05); (3)
down-regulated the mRNA levels of ZO-1, occludin [only in middle intestine (MI)],
claudin-b, claudin-c, claudin-f, claudin-3c, claudin-7a, claudin-7b and claudin
11, and up-regulated the mRNA levels of claudin-12 and claudin-15a (P < .05),
which might be partly linked to Kelch-like-ECH-associated protein 1a (Keap1a)/NF
E2-related factor 2 (Nrf2), p38 mitogen-activated protein kinase (p38MAPK) and
myosin light chain kinase (MLCK) signalling in the intestines of fish. However,
the activities and mRNA levels of MnSOD, the mRNA levels of Keap1b, c-Jun N
terminal protein kinase (JNK) and claudin-15b in three intestinal segments, and
the mRNA levels of occludin in the proximal intestine (PI) and distal intestine
(DI) were not affected by graded levels of PN. These data indicate that PN
deficiency could disturb the intestinal physical barrier function of fish.
Additionally, based on the quadratic regression analysis for MDA content and GST
activity, the dietary PN requirements for young grass carp were estimated as 4.85
and 5.02 mg/kg diet, respectively.
PMID- 29339046
TI - Stereotactic body radiation therapy (SBRT) for high-risk prostate cancer: Where
are we now?
AB - PURPOSE: Stereotactic body radiation therapy (SBRT) is increasingly being used
for the management of localized prostate cancer. This trend combined with
declining use of brachytherapy (BT) has pushed issues and questions regarding the
use of SBRT to the forefront. A systematic literature review was conducted to
review the current evidence of biochemical disease-free survival (bDFS) and
toxicity of SBRT in high-risk (HR) prostate cancer. METHODS AND MATERIALS: A
search was carried out on the PubMed and Embase databases. Studies were included
if HR patients were treated using SBRT monotherapy or as a boost and bDFS was
reported. Selected high-dose-rate (HDR) BT studies including HR patients from
published reviews were selected to compare with SBRT results. Data from recent
published phase 3 trials involving HR patients were also compared. RESULTS: Our
search yielded 8862 articles. Of these, 20 studies with a median follow-up from
1.6 to 7 years were included in this review. The 5-year bDFS was 81% to 91% in
monotherapy studies and 90% to 98% in boost studies. For reference, 19 studies
that reported treating HR patients with HDR monotherapy or boost were selected.
The 5-year bDFS in HDR monotherapy studies and boost studies was 85% to 93% and
72% to 93%, respectively. The incidence of late grade 3 genitourinary toxicity
was 0% to 4.4% and 0% to 2.3% in SBRT monotherapy and SBRT boost studies,
respectively. CONCLUSION: The evidence for SBRT in HR patients in this review is
based on observational studies with relatively few patients and short follow-up
(level III evidence). Based on these data and the principles surrounding
treatment, SBRT boost should ideally be validated in clinical trials. SBRT
monotherapy should be used cautiously in highly selected HR patients outside of a
clinical trial. SUMMARY: Stereotactic body radiation therapy (SBRT) is
increasingly being used for the management of clinically localized prostate
cancer. This trend, combined with the decline in the use of brachytherapy, has
pushed issues and questions regarding the use of SBRT to the forefront. A
systematic literature review was conducted to establish the current evidence of
biochemical and toxicity outcomes of SBRT in high-risk prostate cancer.
PMID- 29339047
TI - The impact of semilateral decubitus position on the dose-volume parameters of the
heart and lung for left sided breast cancer patients: A comparative dosimetric
study.
AB - PURPOSE: When treating breast cancer with radiation therapy, the impact of
treatment position on heart and lung dose-volume parameters (DVPs) is largely
dependent on the maximal heart distance (MHD) and central lung distance (CLD). We
evaluate how much heart and lung sparing can be achieved using the semilateral
decubitus (SLD) position without and with breath hold compared with the standard
supine position for left-sided breast cancer patients. A secondary aim was to
investigate the impact of MHD and CLD on heart and lung DVPs. METHODS AND
MATERIALS: Thirty-five left-sided breast cancer patients were simulated in
supine, free breathing SLD, and SLD with breath hold positions. A dosimetry plan
was developed for each of these and 3 plans were compared for target coverage and
organs at risk sparing. A correlation between CLD, MHD, and planning target
volume, and heart and ipsilateral lung DVPs was tested. RESULTS: SLD breath hold
position showed a significant reduction in percentage of heart receiving >=5 Gy
(V5Gy), V10Gy, V25Gy, V30Gy, mean dose and maximum dose (P < .001), ipsilateral
lung V20Gy, and mean dose compared with supine (P < 001) and free breathing SLD
(P = .003 and .006). There was also a significant reduction in the heart DVPs (P
< .001) and ipsilateral lung DVPs (P < .001 and .007) with free breathing SLD
compared with the supine position. SLD with or without breath hold were
associated with significant reduction in MLD (P < .001) and CLD (P = .030 and
.003) compared with the supine position. CONCLUSION: Treatment plans for patients
in the SLD position with or without breath hold for left-sided breast cancer
patients demonstrated a superior heart and lung sparing compared with the supine
position due to significant reduction in MHD and CLD. MHD and CLD are important
simulation factors that affect the heart and lung DVP.
PMID- 29339049
TI - Genotype and homology analysis of pathogenic and colonization strains of Candida
albicans from hospitalized neonates.
AB - BACKGROUND: To detect the genotypes of pathogenic and colonization Candida
albicans strains and to reveal whether there was a homologous relationship
between these strains. METHODS: Pathogenic and colonization isolates were
collected from infants in the NICU of Shenzhen People's Hospital (Shenzhen,
People's Republic of China). rDNA identification, multilocus sequence typing
(MLST), and multi-loci variable number tandem repeat analysis (MLVA) were used
for species confirmation, strain identification, phylogenetic tree clustering,
and assessment of homology among the pathogenic and colonization strains.
RESULTS: All 48 isolates belonged to C. albicans species; 12 were collected from
premature infants with fungal sepsis. These isolates generated 5 sequence types
(ST1867, ST2551, ST2552, ST2937, and ST2945) and were designated as pathogenic
strains. The other 36 isolates were collected from the infants without fungal
infection; 9 sequence types were detected and designated as the colonization
strains. In the phylogenetic tree, the upper branch consisted of a 4 degrees
clade composed of 20 colonization isolates designated to 3 strains, and 4
pathogenic isolates designated to 1 strain; a 5 degrees clade composed of 8
pathogenic isolates designated to 3 strains; and a 4 degrees clade consisting 1
pathogenic isolate designated to 1 strain and 4 colonization isolates designated
to 2 strains. The lower branch consisted of a 3 degrees clade composed of 6
colonization isolates designated to 2 strains and a control pathogenic isolate,
and a 3 degrees clade composed of 5 colonization isolates designated to 2
strains. CONCLUSION: Although there was no core ST detected to specify
pathogenicity or colonization of C. albicans, the genotypes of the colonization
strains were different from those of the pathogenic strains. Most of the
colonization and pathogenic strains were highly homologous within their
classifications while some pathogenic strains had genomes highly homologous with
those of colonization strains and clustered in heterogeneous groups.
PMID- 29339048
TI - Intrarenal fat deposition does not interfere with the measurement of single
kidney perfusion in obese swine using multi-detector computed tomography.
AB - BACKGROUND: Altered vascular structure or function in several diseases may impair
renal perfusion. Multi-detector computed tomography (MDCT) is a non-invasive tool
to assess single-kidney perfusion and function based on dynamic changes in tissue
attenuation during contrast media transit. However, changes in basal tissue
attenuation might hamper these assessments, despite background subtraction.
Evaluation of iodine concentration using the dual-energy (DECT) MDCT mode allows
excluding effects of basal values on dynamic changes in tissue attenuation. We
tested whether decreased basal kidney attenuation secondary to intrarenal fat
deposition in swine obesity interferes with assessment of renal perfusion using
MDCT. METHODS: Domestic pigs were fed a standard (lean) or a high
cholesterol/carbohydrate (obese) diet (n = 5 each) for 16 weeks, and both kidneys
were then imaged using MDCT/DECT after iodinated contrast injection. DECT images
were post-processed to generate iodine and virtual-non-contrast (VNC) datasets,
and the MDCT kidney/aorta CT number (following background subtraction) and DECT
iodine ratios calculated during the peak vascular phase as surrogates of renal
perfusion. Intrarenal fat was subsequently assessed with Oil-Red-O staining.
RESULTS: VNC maps in obese pigs revealed decreased basal cortical attenuation,
and histology confirmed increased renal tissue fat deposition. Nevertheless, the
kidney/aorta attenuation and iodine ratios remained similar, and unchanged
compared to lean pigs. CONCLUSIONS: Despite decreased basal attenuation secondary
to renal adiposity, background subtraction allows adequate assessment of kidney
perfusion in obese pigs using MDCT. These observations support the feasibility of
renal perfusion assessment in obese subjects using MDCT.
PMID- 29339050
TI - Neonatal solid tumors: A therapeutic challenge.
PMID- 29339051
TI - An unusual GFAP mutation in a Taiwanese child with infantile Alexander disease.
PMID- 29339052
TI - Neurophysiological effects in cortico-basal ganglia-thalamic circuits of
antidyskinetic treatment with 5-HT1A receptor biased agonists.
AB - Recently, the biased and highly selective 5-HT1A agonists, NLX-112, F13714 and
F15599, have been shown to alleviate dyskinesia in rodent and primate models of
Parkinson's disease, while marginally interfering with antiparkinsonian effects
of levodopa. To provide more detailed information on the processes underlying the
alleviation of dyskinesia, we have here investigated changes in the spectral
contents of local field potentials in cortico-basal ganglia-thalamic circuits
following treatment with this novel group of 5-HT1A agonists or the prototypical
agonist, 8-OH-DPAT. Dyskinetic symptoms were consistently associated with 80 Hz
oscillations, which were efficaciously suppressed by all 5-HT1A agonists and
reappeared upon co-administration of the antagonist, WAY100635. At the same time,
the peak-frequency of fast 130 Hz gamma oscillations and their cross-frequency
coupling to low-frequency delta oscillations were modified to a different extent
by each of the 5-HT1A agonists. These findings suggest that the common
antidyskinetic effects of these drugs may be chiefly attributable to a reversal
of the brain state characterized by 80 Hz gamma oscillations, whereas the
differential effects on fast gamma oscillations may reflect differences in
pharmacological properties that might be of potential relevance for non-motor
symptoms.
PMID- 29339053
TI - Upregulation of NLRP3 via STAT3-dependent histone acetylation contributes to
painful neuropathy induced by bortezomib.
AB - Painful neuropathy, as a severe side effect of chemotherapeutic bortezomib, is
the most common reason for treatment discontinuation. However, the mechanism by
which administration of bortezomib leads to painful neuropathy remains unclear.
In the present study, we found that application of bortezomib significantly
increased the expression of NOD-like receptor family pyrin domain containing 3
(NLRP3) and phosphorylated signal transducer and activator of transcription-3
(STAT3) in dorsal root ganglion (DRG). Intrathecal injection of NLRP3 siRNA
significantly prevented the mechanical allodynia induced by bortezomib treatment,
and intrathecal injection of recombinant adeno-associated virus vector encoding
NLRP3 markedly decreased paw withdrawal threshold of naive rats. Furthermore, the
expressions of p-STAT3 were colocalized with NLRP3-positive cells in DRG neurons,
and inhibition of STAT3 by intrathecal injection of AAV-Cre-GFP into
STAT3flox/flox mice or inhibitor S3I-201 suppressed the upregulation of NLRP3 and
mechanical allodynia induced by bortezomib treatment. Chromatin
immunoprecipitation further found that bortezomib increased the recruitment of
STAT3, as well as the acetylation of histone H3 and H4, in the NLRP3 promoter
region in DRG neurons. Importantly, inhibition of the STAT3 activity by using S3I
201 or DRG local deficiency of STAT3 also significantly prevented the upregulated
H3 and H4 acetylation in the NLRP3 promoter region following bortezomib
treatment. Altogether, our results suggest that the upregulation of NLRP3 in DRG
via STAT3-dependent histone acetylation is critically involved in bortezomib
induced mechanical allodynia.
PMID- 29339054
TI - The dynamics of vector-borne relapsing diseases.
AB - In this paper, we describe the dynamics of a vector-borne relapsing disease, such
as tick-borne relapsing fever, using the methods of compartmental models. After
some motivation and model description we provide a proof of a conjectured general
form of the reproductive ratio R0, which is the average number of new infections
produced by a single infected individual. A disease free equilibrium undergoes a
bifurcation at R0=1 and we show that for an arbitrary number of relapses it is a
transcritical bifurcation with a single branch of endemic equilibria that is
locally asymptotically stable for R0 sufficiently close to 1. Furthermore, we
show there is no backwards bifurcation. We then show that these results can be
extended to variants of the model with an example that allows for variation in
the number of relapses before recovery. Finally, we discuss implications of our
results and directions for future research.
PMID- 29339055
TI - Emotional States and Sudden Death.
PMID- 29339056
TI - Do Not Resuscitate Tattoos.
PMID- 29339057
TI - Hidden Giant: Medium Vessel Vasculitis as a Cause for Unresolving Fever.
PMID- 29339058
TI - Carboxylic group riched graphene oxide based disposable electrochemical
immunosensor for cancer biomarker detection.
AB - In this work, we have developed for the first time a carboxylic group riched
graphene oxide based disposable electrochemical immunosensor for cancer biomarker
detection using methylene blue (MB). The developed immunosensor is highly
sensitive for detection of biomarker Mucin1 (MUC1) in human serum samples.
Development of this disposable electrochemical immunosensor was premeditated by
applying specific monoclonal antibodies against MUC1. In this method, we explored
highly conductive surface of carboxylic group (-COOH-) rich graphene oxide (GO)
on screen-printed carbon electrodes (SPCE). This modified GO-COOH-SPCE was
employed for the detection of MUC1 protein based on the reaction with methylene
blue (MB) redox probe using differential pulse voltammetry (DPV) technique.
Developed immunosensor exhibited good detection range for MUC1 with excellent
linearity (0.1 U/mL- 2 U/mL), with a limit of detection of 0.04 U/mL. Upon
potential application of developed biosensor, good recoveries were recorded in
the range of 96-96.67% with % R.S.D 4.2. Analytical performance of the developed
immunosensor assures the applicability in clinical diagnostic applications.
PMID- 29339059
TI - Moving toward rapid and low-cost point-of-care molecular diagnostics with a
repurposed 3D printer and RPA.
AB - Traditionally, the majority of nucleic acid amplification-based molecular
diagnostic tests are done in centralized settings. In recent years, point-of-care
tests have been developed for use in low-resource settings away from central
laboratories. While most experts agree that point-of-care molecular tests are
greatly needed, their availability as cost-effective and easy-to-operate tests
remains an unmet goal. In this article, we discuss our efforts to develop a
recombinase polymerase amplification reaction-based test that will meet these
criteria. First, we describe our efforts in repurposing a low-cost 3D printer as
a platform that can carry out medium-throughput, rapid, and high-performing
nucleic acid extraction. Next, we address how these purified templates can be
rapidly amplified and analyzed using the 3D printer's heated bed or the
deconstructed, low-cost thermal cycler we have developed. In both approaches,
real-time isothermal amplification and detection of template DNA or RNA can be
accomplished using a low-cost portable detector or smartphone camera. Last, we
demonstrate the capability of our technologies using foodborne pathogens and the
Zika virus. Our low-cost approach does not employ complicated and high-cost
components, making it suitable for resource-limited settings. When integrated and
commercialized, it will offer simple sample-to-answer molecular diagnostics.
PMID- 29339060
TI - Quantification of a recombinant antigen in an immuno-stimulatory whole yeast cell
based therapeutic vaccine.
AB - Therapeutic vaccines represent an emerging class of immune-modulatory treatments
for cancer, infections, and chronic diseases. One such vaccine was designed as an
immune stimulator of the T cell response against HBV antigens to eliminate HBV
infected cells and offer a therapeutic avenue to treat patients suffering from
chronic hepatitis B infection. Whole deactivated Saccharomyces cerevisiae cells
expressing a recombinant fusion of HBV X, S and Core antigens elicit T cell
responses in mice and activate human T cells linked with viral clearance. As the
therapeutic efficacy of the yeast-based vaccine relies on the production of the
recombinant antigen, analytical methods designed to accurately and precisely
quantitate the fusion protein in the midst of all the yeast proteins are
necessary. We report the development and characterization of western blot,
quantitative ELISA and mass spectrometry based orthogonal methods to support the
assessment of manufacturing consistency.
PMID- 29339061
TI - Dose-dependent photochemical/photothermal toxicity of indocyanine green-based
therapy on three different cancer cell lines.
AB - The Food and Drug Administration-approved Indocyanine Green can be used as a
photosensitizer to kill cancer cells selectively. Although indocyanine green is
advantageous as a photosensitizer in terms of strong absorption in the near
infrared region, indocyanine green-based cancer treatment is still not approved
as a clinical method. Some reasons for this are aggregation at high
concentrations, rapid clearance of the photosensitizer from the body, low singlet
oxygen quantum yield, and the uncertainty concerning its action mechanism. This
in vitro study focuses on two of these points: "what is the cell inhibition
mechanism of indocyanine green-based therapy?" and "how the dose-dependent
aggregation problem of indocyanine green alters its cell inhibition efficiency?"
The following experiments were conducted to provide insight into these points.
Nontoxic doses of indocyanine green and near-infrared laser were determined. The
aggregation behavior of indocyanine green was verified through experiments. The
singlet oxygen quantum yield of indocyanine green at different concentrations
were calculated. Various indocyanine green and energy densities of near-infrared
light were applied to prostate cancer, neuroblastoma, and colon cancer cells. An
MTT assay was performed at the end of the first, second, and third days following
the treatments to determine the cell viability. Temperature changes in the medium
during laser exposure were recorded. ROS generation following the treatment was
verified by using a Total Reactive Oxygen Species detection kit. An apoptosis
detection test was performed to establish the cell death mechanism and, finally,
the cellular uptakes of the three different cells were measured. According to the
results, indocyanine green-based therapy causes cell viability decrease for three
cancer cell lines by means of excessive reactive oxygen species production.
Different cells have different sensitivities to the therapy possibly because of
the differentiation level and structural differences. The singlet oxygen
generation of indocyanine green decreases at high concentrations because of
aggregation. Nevertheless, better cancer cell killing effect was observed at
higher photosensitizer concentrations. This result reveals that the cellular
uptake of indocyanine green was determinant for better cancer cell inhibition.
PMID- 29339062
TI - The effect of humeral tunnel locations on radiographic tunnel changes in baseball
players following medial ulnar collateral ligament reconstruction: comparison of
anatomic and nonanatomic locations.
AB - BACKGROUND: There has been no study on radiologic changes after medial ulnar
collateral ligament (MUCL) reconstruction and related clinical features. METHODS:
Data from 39 baseball players who underwent MUCL reconstruction were collected
and analyzed. The baseball players were classified into 2 groups according to the
starting point of the humeral tunnel: (1) the lower tip of the medial epicondyle
(group NA, n = 21) and (2) the remnant of the MUCL (group A, n = 18). Bone tunnel
characteristics and changes were evaluated by computed tomography (CT) at 3 and 9
months postoperatively. Outcome measures consisted of the visual analog scale,
range of motion (ROM), the Conway scale, and the presence of ulnar nerve
irritation postoperatively. RESULTS: The mean diameter of the humeral entry was
4.0 mm (range, 3.4-5.1 mm) on the first CT scan, which increased to 5.5 mm
(range, 3.2-7.2 mm) on the follow-up CT scan (P < .001). The mean diameter of the
ulnar tunnel was 2.8 mm (range, 1.1-3.3 mm) on the first CT scan, which decreased
to 1.6 mm (range, 0-4.3 mm) on the follow-up CT scan (P < .001). The between
group comparison revealed no differences in the changes in the diameter of the
humeral and ulnar tunnels. A statistically significant correlation was not found
between athletic performance measured by the Conway scale and the radiologic
changes on CT evaluation (P = .182). Group A showed improvement in extension from
7 degrees preoperatively to 1 degrees postoperatively (P < .001) and in flexion
from 126 degrees preoperatively to 136 degrees postoperatively (P < .001),
while group NA did not achieve statistical significance in ROM improvement after
the operation. CONCLUSIONS: Humeral tunnel widening was commonly observed, while
the ulnar tunnel was maintained or became narrowed conversely. The humeral tunnel
placements did not affect tunnel changes after the surgical procedure; however,
MUCL reconstruction with the anatomic location of the humeral tunnel yielded
substantial improvement in elbow ROM.
PMID- 29339064
TI - Factors Associated With Early Graft Detachment in Primary Descemet Membrane
Endothelial Keratoplasty.
AB - PURPOSE: To evaluate the risk factors for early graft detachment in Descemet
membrane endothelial keratoplasty (DMEK). DESIGN: Case-control study. METHODS:
Participants: A total of 173 donor corneas and 173 eyes of the patients following
DMEK or DMEK in combination with phacoemulsification and intraocular lens
implantation were included. INTERVENTION: Pre-stripped DMEK grafts were
transplanted using pull-through technique. At the end of surgery, the anterior
chamber was filled with air, which was removed 3 hours later only if pupillary
block was suspected. Rebubbling was performed in all cases with graft detachment,
independently of its extension, as documented by means of anterior segment
optical coherence tomography. The donor characteristics were collected from the
eye bank database and matched with the recipient database. MAIN OUTCOME MEASURES:
Donor and recipient characteristics affecting graft detachment using univariate
and multivariate analysis. RESULTS: The combination of DMEK with cataract removal
and IOL implantation (odds ratio [OR] = 5.31, 95% confidence interval [CI] 2.03
13.86, P < .002) and air fill of <=75% of anterior chamber height at 2-3 hours
postoperatively (OR = 2.66, 95% CI 1.12-6.34, P = .027) were found to be
independent risk factors for postoperative graft detachment. CONCLUSIONS:
Cataract removal at the time of DMEK is a risk factor for early graft detachment
and therefore sequential surgery may be preferred over combined surgery in an
attempt at minimizing rebubbling. Air level in the anterior chamber should be
monitored and maintained above 75% in the early hours following surgery.
PMID- 29339065
TI - Accommodative Esotropia Treatment Plan Utilizing Simultaneous Strabismus Surgery
and Photorefractive Keratectomy.
AB - PURPOSE: Accommodative esotropia is a common cause of acquired esotropia.
Pathogenesis varies among patients but usually includes excessive hyperopia and a
high accommodative convergence/accommodation ratio or tight medial recti. The
present study reviews an individualized treatment plan combining photorefractive
keratectomy (PRK) and strabismus surgery to correct these problems. DESIGN: This
study is a retrospective, interventional case series. METHODS: Records for 15
patients who were treated for accommodative esotropia were reviewed. Patient ages
ranged from 11 to 19 years. PRK and strabismus surgery were performed on 11
patients, and PRK only on 4 patients. The goal was to create a physiologic
refractive error, good visual acuity (VA), and straight eyes without correction.
RESULTS: All patients were spectacle free at 6-month follow-up. Twenty-four of 30
eyes had VA equal to preoperative VA without correction. Three eyes had a 1-line
reduction and 2-line reduction in VA. The alignment results were +/-10 prism
diopters in 13 of 15 patients. Spherical refractive outcomes were 18 of 30 eyes
within 1 diopter (D) of target and 12 of 30 eyes within 2 D of target.
Astigmatism refractive outcomes were 21 of 30 eyes <1 D, 7 eyes 1-2 D, and 2 eyes
>2 D. Two patients complained of halos at night, and 1 patient had peripheral
corneal haze. CONCLUSION: Simultaneous PRK and strabismus surgery is safe and
effective in treating accommodative esotropia. An individualized treatment plan
can result in a physiologic refractive error, good VA, and a spectacle-free
existence.
PMID- 29339063
TI - Evolution of Intravitreal Therapy for Retinal Diseases-From CMV to CNV: The LXXIV
Edward Jackson Memorial Lecture.
AB - PURPOSE: To present the evolution of intravitreal therapy for retinal diseases
and its impact on clinical practice. DESIGN: Retrospective literature review and
personal perspective. METHODS: Retrospective literature review and personal
perspective. RESULTS: Pharmacotherapeutic advances in retinal disease have been
remarkable over the last 25 years. Almost all of the new drugs developed have
required intravitreal administration to be highly effective, leading to an
exponential increase in the annual number of intravitreal injections given. The
use of intravitreal antibiotic injections to treat endophthalmitis, usually on a
one-time basis, first familiarized ophthalmologists with this method of drug
delivery. Ganciclovir was the first widely available, relatively inexpensive
compounded drug that was used for repeat intravitreal injection to treat a
chronic retinal disease, followed by triamcinolone for diabetic macular edema and
bevacizumab for neovascular age-related macular degeneration. Ganciclovir was
formulated for sustained-release drug delivery to avoid frequent intravitreal
injections, a goal that has been more elusive for anti-VEGF drugs. Political
obstacles encountered while conducting some of the trials to evaluate these
treatments were substantial. Addressing the issues they raised led to important
national policy changes that will impact the conduct of future clinical trials.
The first comparative efficacy trial of intravitreal therapies was the Comparison
of AMD Treatments Trials (CATT). The primary results from CATT and the many
publications that followed continue to shape the use of intravitreal therapy
today. CONCLUSION: Intravitreal therapy has proven highly effective for the
treatment of many retinal diseases. The treatment burden for patients from
numerous injections, the cost to health care systems, and the impact on workflows
in clinical practice have been substantial. Efforts to develop effective
intravitreal therapies with reduced treatment burden and cost are ongoing.
PMID- 29339066
TI - Apolipoprotein A-I: A favorable prognostic marker in infective endocarditis.
AB - BACKGROUND: Decreased apolipoprotein A-I (apoA-I) and high-density lipoprotein
cholesterol (HDL-C) are common in inflammation and sepsis. No study with a large
sample size has been performed to investigate the prognostic value of apoA-I or
HDL-C in infective endocarditis (IE). OBJECTIVE: The present study aimed to
explore the prognostic value of apoA-I and HDL-C for adverse outcomes in IE
patients. METHODS: Patients with a definite diagnosis of IE between January 2009
and July 2015 were enrolled and divided into 3 groups according to their apoA-I
tertiles at admission. Univariate and multivariate analyses were performed to
evaluate the relationship of apoA-I and HDL-C with clinical outcomes. RESULTS: Of
the 593 included patients, 40 (6.7%) died in hospital. Patients with lower apoA-I
experienced markedly higher rates of in-hospital mortality (10.7%, 7.0%, and 2.5%
in tertiles 1-3, respectively; P = .006) and major adverse clinical events
(32.5%, 24.1%, and 8.6% in tertiles 1-3, respectively; P < .001). ApoA-I (area
under the curve, 0.671; P < .001) and HDL-C (area under the curve, 0.672; P <
.001) had predictive values for in-hospital death. Multivariate logistic
regression showed that apoA-I <0.90 g/L and HDL-C <0.78 mmol/L were independent
risk predictors for in-hospital death. A multivariate Cox proportional hazard
analysis revealed that apoA-I (increments of 1 g/L; hazard ratio, 0.36; 95%
confidence interval, 0.15-0.87; P = .023) and HDL-C (increments of 1 mmol/L;
hazard ratio, 0.38; 95% confidence interval, 0.18-0.83; P = .015) were
independently associated with long-term mortality. CONCLUSIONS: ApoA-I and HDL-C
were inversely associated with adverse IE prognosis.
PMID- 29339067
TI - Molecular characterization and function of beta-N-acetylglucosaminidase from
ridgetail white prawn Exopalaemon carinicauda.
AB - Chitin degradation is catalyzed by a two-component chitinolytic enzyme system,
chitinase and beta-N-acetylglucosaminidase (NAGase). In this paper, the full
length cDNA sequence encoding NAGase (EcNAG) was obtained from Exopalaemon
carinicauda. The deduced amino acid sequence of EcNAG open reading frame (ORF)
contained one Glycohydro_20b2 domain and one Glyco_hydro_20 domain. Based on the
cDNA sequence, the genomic structure of EcNAG was characterized and it was
composed of six exons and five introns. EcNAG mRNA majorly expressed in the
hepatopancreas and epidermis. During the molting stages, EcNAG mRNA expression
was well-regulated and its expression reached the highest level at the molting
stage E. In addition, EcNAG was recombinant expressed in Pichia pastoris and the
partial enzymatic characterization of recombinant EcNAG was confirmed. After
being challenged with Vibrio parahaemolyticus and Aeromonas hydrophila, the
expression of EcNAG was up-regulated significantly at 6 h and reached the peak at
12 h. And then, the expression began to down-regulated and came to the normal
level at 72 h. It is helpful to research the relationship between the molt
related hormones and chitinlytic enzymes.
PMID- 29339068
TI - A new miRNA regulator, miR-672, reduces cardiac hypertrophy by inhibiting JUN
expression.
AB - Cardiac hypertrophy is one of the initial symptoms of many heart diseases. We
found that miR-672-5p may participate in the regulation of heart disease
development in mouse, but the association between miR-672-5p and cardiac
hypertrophy remains unclear. In the present study, we found that the abundance of
miR-672-5p decreased in hypertrophic cardiomyocytes induced by phenylephrine,
angiotensin II (Ang II) and insulin-like growth factor 1. Putative target genes
of miR-672-5p were identified using four pipelines, miRWalk, miRanda, RNA22 and
Targetscan, and a total of 834 genes were predicted by all four pipelines. Among
these target genes, 98 were associated with the development of heart disease. PPI
networks showed that the Jun proto-oncogene product (JUN), a subunit of the AP-1
transcription factor, had the highest node degree, and it was defined as the hub
gene of the PPI networks. Luciferase assays showed that miR-672-5p bound to the
3' UTR of the JUN gene and decreased luciferase activity, indicating that JUN is
a target of miR-672-5p. Finally, we found that increasing the abundance of miR
672-5p in cardiomyocytes controlled the relative cell area in Ang II-stimulated
hypertrophic cardiomyocytes. Correspondingly, the abundance of JUN, a target of
miR-672-5p, was decreased in hypertrophic cardiomyocytes on both mRNA and protein
levels, implying that miR-672-5p had suppressive effects on cardiac hypertrophy
through regulating the expression of Jun in cardiomyocytes.
PMID- 29339069
TI - Multiple homologous genes knockout (KO) by CRISPR/Cas9 system in rabbit.
AB - The CRISPR/Cas9 system is a highly efficient and convenient genome editing tool,
which has been widely used for single or multiple gene mutation in a variety of
organisms. Disruption of multiple homologous genes, which have similar DNA
sequences and gene function, is required for the study of the desired phenotype.
In this study, to test whether the CRISPR/Cas9 system works on the mutation of
multiple homologous genes, a single guide RNA (sgRNA) targeting three
fucosyltransferases encoding genes (FUT1, FUT2 and SEC1) was designed. As
expected, triple gene mutation of FUT1, FUT2 and SEC1 could be achieved
simultaneously via a sgRNA mediated CRISPR/Cas9 system. Besides, significantly
reduced serum fucosyltransferases enzymes activity was also determined in those
triple gene mutation rabbits. Thus, we provide the first evidence that multiple
homologous genes knockout (KO) could be achieved efficiently by a sgRNA mediated
CRISPR/Cas9 system in mammals, which could facilitate the genotype to phenotype
studies of homologous genes in future.
PMID- 29339070
TI - Involvement of interferon regulatory factor 3 from the barbel chub Squaliobarbus
curriculus in the immune response against grass carp reovirus.
AB - The barbel chub Squaliobarbus curriculus is an important commercial fish species
in China, and has shown significant resistance to grass carp reovirus (GCRV). In
this study, the cDNA sequence of interferon regulatory factors 3 (IRF3) from
Squaliobarbus curriculus, designated as ScIRF3, was cloned, and its effect
against GCRV was investigated. The full-length 1837 base pair (bp) cDNA of ScIRF3
contained a complete open reading frame of 1374 bp and encoded a putative
polypeptide of 457 amino acid residues. The ScIRF3 protein contained conserved
domains, including an N-terminal DNA-binding domain, a C-terminal IRF association
domain, and a serine-rich domain. Phylogenetic analysis showed that ScIRF3 was
closely clustered with IRF3s from Carassius auratus and Ctenopharyngodon idellus.
Quantitative real-time polymerase chain reaction analysis showed that the
expression levels of ScIRF3 in Squaliobarbus curriculus were the highest in the
spleen and lowest in the muscle. After GCRV infection, expression levels of both
ScIRF3 and type I interferon (IFN) were initially up-regulated and subsequently
down-regulated in the spleen and intestine. Correlation analysis showed that the
expression level of type I IFN is significantly positively correlated with that
of ScIRF3 (Pearson correlation coefficient: 0.883, P: 0.004) in the intestine.
The expression level of type I IFN was also significantly up-regulated and the
GCRV titer was significantly decreased (P < .05) in GCRV-infected ScIRF3
overexpressing Ctenopharyngodon idellus kidney cells. These results indicate that
ScIRF3 may play a role in the type I IFN immune response against GCRV in
Squaliobarbus curriculus and can also inhibit GCRV replication in
Ctenopharyngodon idellus kidney cells.
PMID- 29339071
TI - MiR-155-5p promotes fibroblast cell proliferation and inhibits FOXO signaling
pathway in vulvar lichen sclerosis by targeting FOXO3 and CDKN1B.
AB - Vulvar lichen sclerosis (VLS) is a chronic inflammatory skin disorder. Evidence
is accumulating that microRNAs (miRNAs) exert crucial roles in initiation and
development of a wide range of human diseases. MiR-155-5p has been frequently
reported to be implicated in the tumorigenesis and progression of multiple types
of cancers, however, its biological role in VLS remains unclear. This study aimed
to explore the role of miR-155-5p in VLS and clarify the potential molecular
mechanisms involved. In the present study, miR-155-5p was observed to be
significantly upregulated in VLS tissues. Functional studies showed that miR-155
5p facilitated cell proliferation, accelerated cell cycle progression and
inhibited forkhead box O (FOXO) signaling pathway in fibroblast cells. Mechanical
studies demonstrated that miR-155-5p exerted its promoting effects on fibroblast
cell proliferation via targeting both forkhead box O3 (FOXO3) and cyclin
dependent kinase inhibitor 1B (CDKN1B). Besides, Pearson's correlation analysis
revealed that miR-155-5p expression was negatively correlated with the mRNA
expression of FOXO3 and CDKN1B in VLS tissues. Taken together, our results
indicate that miR-155-5p promotes fibroblast cell proliferation and inhibits FOXO
signaling pathway by negative modulation of both FOXO3 and CDKN1B in VLS, and
that miR-155-5p may be used to be a potential therapeutic target for VLS.
PMID- 29339072
TI - Deep sequencing of a QTL-rich region spanning 128-136Mbp of pig chromosome 15.
AB - The present study shows the characterization of the chromosome 15 (SSC15) region
that is highly rich in quantitative traits loci (QTLs) associated with pork
quality, growth performance, fat and meat carcass contents. The analytic method
that was utilized included targeted enrichment DNA sequencing and RNA
hybridisation probes. The research included two pig breeds (Pulawska and Polish
Landrace) that are significantly different in terms of carcass and meat quality
features. Filtered sequences were aligned to the Sscrofa10.2 assembly genome with
the STAR aligner and GATK HaplotypeCaller was used for identified gene variants
in SSC15 region. In Pulawska pigs, which were characterized by high meat quality,
mutations were predominantly observed in non-coding regions such as introns and
intergenic regions. The highest over 50% frequencies of alternate alleles were
identified in the introns of TNS1, VIL1 and USP37 genes. In the upstream gene
regions of the Polish Landrace pigs, were observed more mutations than in the
upstream gene regions of Pulawska. The present study showed interesting gene
variant panel that could be analyzed in the further association studies in order
to understand the impact on important productive pig traits.
PMID- 29339073
TI - The human GCOM1 complex gene interacts with the NMDA receptor and internexin
alpha.
AB - The known functions of the human GCOM1 complex hub gene include transcription
elongation and the intercalated disk of cardiac myocytes. However, in all
likelihood, the gene's most interesting, and thus far least understood, roles
will be found in the central nervous system. To investigate the functions of the
GCOM1 gene in the CNS, we have cloned human and rat brain cDNAs encoding novel,
105 kDa GCOM1 combined (Gcom) proteins, designated Gcom15, and identified a new
group of GCOM1 interacting genes, termed Gints, from yeast two-hybrid (Y2H)
screens. We showed that Gcom15 interacts with the NR1 subunit of the NMDA
receptor by co-expression in heterologous cells, in which we observed bi
directional co-immunoprecipitation of human Gcom15 and murine NR1. Our Y2H
screens revealed 27 novel GCOM1 interacting genes, many of which are synaptic
proteins and/or play roles in neurologic diseases. Finally, we showed, using rat
brain protein preparations, that the Gint internexin-alpha (INA), a known
interactor of the NMDAR, co-IPs with GCOM1 proteins, suggesting a GCOM1-GRIN1-INA
interaction and a novel pathway that may be relevant to neuroprotection.
PMID- 29339074
TI - Identification and characterization of a doublesex gene which regulates the
expression of insulin-like androgenic gland hormone in Fenneropenaeus chinensis.
AB - The doublesex and its homologue genes are important regulators of sexual
differentiation which are conserved among animal kingdom. In the present study,
we reported a doublesex gene (designated as FcDsx) identified from the Chinese
shrimp F. chinensis. The gene structure, nucleotide and deduced amino acid
sequences of FcDsx were characterized. The results showed that the deduced amino
acid sequence of FcDsx had the common features of Dsx proteins, including a
doublesex/male abnormal 3 (DM) domain, an oligomerization domain and a predicted
monopartite nuclear localization signal. The expression patterns of FcDsx in
different tissues and developmental stages were detected. FcDsx exhibited a sex
biased expression patterns in different tissues and its expression level
increased along with developmental stages. In addition, its regulation on the
expression of FcIAG, a gene important for sexual differentiation of male
crustacean, was also analyzed. Putative Dsx binding site was identified on the
promoter region of FcIAG and knockdown of FcDsx could reduce the expression of
FcIAG, which suggested that FcDsx might be the upstream regulator of FcIAG. The
present data indicated that FcDsx gene might involve in shrimp sexual
differentiation process.
PMID- 29339075
TI - Up-regulated lncRNA-MSX2P1 promotes the growth of IL-22-stimulated keratinocytes
by inhibiting miR-6731-5p and activating S100A7.
AB - Competitive endogenous RNAs (ceRNAs) regulate RNA transcripts by competing for
shared miRNAs and play critical roles in disease development. Psoriasis is a long
lasting, recurring chronic inflammatory skin disease characterized by
hyperproliferation of keratinocytes. The keratinocyte response is triggered by
the activation of inflammatory cytokines, like interleukin-22 (IL-22). We used
lncRNA array analysis to detect differentially expressed lncRNAs in skin (HaCaT)
cells treated with or without IL-22. We used hematoxylin and eosin (H&E) staining
to determine the pathological changes in skin cells and immunohistochemistry to
evaluate the expression of S100A7. We used qRT-PCR and Western blotting to detect
the expression levels of MSX2P1 and S100A7. We down-regulated the expression of
MSX2P1 by infecting with lentiviral-vector shRNA. We measured cell proliferation,
cell cycle status, and apoptosis by the CCK-8 assay, flow cytometry, and Annexin
V-FITC/PI staining, respectively. In addition, we used the luciferase reporter
gene assay to determine the relationships between MSX2P1 or miR-6731-5p and
S100A7, respectively. LncRNA array analysis revealed that 103 lncRNAs were up
regulated and 51 were down-regulated. Furthermore, qRT-PCR showed that the mRNAs
levels of MSX2P1 was significantly altered in HaCaT cells treated with IL-22,
compared with control cells; and MSX2P1 was mainly in the cytoplasm. Based on the
IL-22-stimulated lncRNA-associated ceRNA network, we selected MSX2P1-miR-6731-5p
S100A7 for further study. H&E staining exhibited characteristic features specific
to psoriatic lesions. Immunohistochemistry demonstrated significantly increased
expression levels of S100A7 in psoriatic lesions, compared with normal skin
tissue. We observed a positive correlation between lncRNA-MSX2P1 expression and
S100A7 expression. In addition, miR-6731-5p suppressed proliferation, accelerated
apoptosis in IL-22-stimulated keratinocytes, and decreased the expressions of
S100A7, IL-12beta, IL-23, HLA-C, CCHCR1, TNF-alpha, and NF-kappaB proteins. Our
data demonstrated that MSX2P1 facilitate the progression and growth of IL-22
stimulated keratinocytes by inhibiting miR-6731-5p and activating S100A7. We
speculate that the biological network of MSX2P1-miR-6731-5p-S100A7 is a potential
novel therapeutic target for the future treatment of psoriasis.
PMID- 29339076
TI - Inhibition of miR-361-5p suppressed pulmonary artery smooth muscle cell survival
and migration by targeting ABCA1 and inhibiting the JAK2/STAT3 pathway.
AB - MicroRNAs play a crucial role in the progression of pulmonary arterial
hypertension (PAH). The aim of this study was to investigate the effect of miR
361-5p on the proliferation, migration and apoptosis of pulmonary artery smooth
muscle cells (PASMCs) that under the treatment of hypoxia and explore the
underlying mechanisms. The results proved that hypoxia noticeably up-regulated
the expression of miR-361-5p in PASMCs in comparison to the normoxia-treated
cells, while TNF-alpha and IL-6 stimulation had no obvious effects on miR-361-5p
level. Hypoxia induced miR-361-5p elevation in a HIF-1alpha-dependent manner.
Inhibition of miR-361-5p dramatically inhibited hypoxia-induced cell
proliferation and migration. miR-361-5p inhibition also rescued hypoxia exposure
caused suppression of PASMCs apoptosis. In addition, the results showed that
ABCA1 was a direct target of miR-361-5p and was down-regulated in hypoxia-induced
PASMCs. Hypoxia and TNF-alpha or IL-6 stimulation significantly inhibited ABCA1
expression. In addition, overexpression of ABCA1 enhanced the effect of miR-361
5p on hPASMCs. Furthermore, the inhibition of miR-361-5p significantly down
regulated the expression level of p-JAK2 and p-STAT3. In conclusion, it may
suggest that the suppression of miR-361-5p suppressed PASMC survival and
migration by targeting ABCA1 and inhibiting the JAK2/STAT3 pathway.
PMID- 29339077
TI - How context features modulate the involvement of the working memory system during
discourse comprehension.
AB - Using functional magnetic resonance imaging (fMRI), we investigated the effects
of context features on the involvement of the working memory (WM) system during
discourse comprehension. During the fMRI scan, participants were asked to read
two-sentence discourses in which the topic of the second sentence was either
maintained, or was shifted from, the topic of the first. Changes in the level of
coherence between the two sentences as well as context length were also
investigated across discourse items. The WM system was identified with a verbal N
back task. Analysis of the reading comprehension task revealed that within the WM
system, stronger activation in the left inferior frontal gyrus corresponded with
increased bridging coherence demands between sentences, while greater activation
in the left inferior and middle frontal gyri, bilateral superior frontal gyri,
and bilateral inferior parietal lobules corresponded with increased context
length. Topic variation showed no effect on activation of the WM system. These
results provide new insights into understanding how different levels of context
features modulate activation of the subcomponents of the WM system and indicate a
role for the left inferior frontal gyrus as a core component of the WM system
supporting discourse processing.
PMID- 29339078
TI - Analytical and pre-analytical performance characteristics of a novel cartridge
type blood gas analyzer for point-of-care and laboratory testing.
AB - BACKGROUND: Point-of-care blood gas test results may benefit therapeutic decision
making by their immediate impact on patient care. We evaluated the (pre
)analytical performance of a novel cartridge-type blood gas analyzer, the GEM
Premier 5000 (Werfen), for the determination of pH, partial carbon dioxide
pressure (pCO2), partial oxygen pressure (pO2), sodium (Na+), potassium (K+),
chloride (Cl-), ionized calcium (iCa2+), glucose, lactate, and total hemoglobin
(tHb). METHODS: Total imprecision was estimated according to the CLSI EP5-A2
protocol. The estimated total error was calculated based on the mean of the range
claimed by the manufacturer. Based on the CLSI EP9-A2 evaluation protocol, a
method comparison with the Siemens RapidPoint 500 and Abbott i-STAT CG8+ was
performed. Obtained data were compared against preset quality specifications.
Interference of potential pre-analytical confounders on co-oximetry and
electrolyte concentrations were studied. RESULTS: The analytical performance was
acceptable for all parameters tested. Method comparison demonstrated good
agreement to the RapidPoint 500 and i-STAT CG8+, except for some parameters
(RapidPoint 500: pCO2, K+, lactate and tHb; i-STAT CG8+: pO2, Na+, iCa2+ and tHb)
for which significant differences between analyzers were recorded. No
interference of lipemia or methylene blue on CO-oximetry results was found. On
the contrary, significant interference for benzalkonium and hemolysis on
electrolyte measurements were found, for which the user is notified by an
interferent specific flag. CONCLUSION: Identification of sample errors from pre
analytical sources, such as interferences and automatic corrective actions, along
with the analytical performance, ease of use and low maintenance time of the
instrument, makes the evaluated instrument a suitable blood gas analyzer for both
POCT and laboratory use.
PMID- 29339079
TI - Diagnostic Usefulness of Combination of Diffusion-weighted Imaging and T2WI,
Including Apparent Diffusion Coefficient in Breast Lesions: Assessment of
Histologic Grade.
AB - PURPOSE: This study aimed to compare the diagnostic values of a combination of
diffusion-weighted imaging and T2-weighted imaging (DWI-T2WI) with dynamic
contrast-enhanced magnetic resonance imaging (DCE-MRI), and to evaluate the
correlation of DWI with the histologic grade in breast cancer. MATERIALS AND
METHODS: This study evaluated a total of 169 breast lesions from 136 patients who
underwent both DCE-MRI and DWI (b value, 1000s/mm2). Morphologic and kinetic
analyses for DCE-MRI were classified according to the Breast Imaging-Reporting
and Data System. For the DWI-T2WI set, a DWI-T2WI score for lesion
characterization that compared signal intensity of DWI and T2WI (benign: DWI-T2WI
score of 1, 2; malignant: DWI-T2WI score of 3, 4, 5) was used. The diagnostic
values of DCE-MRI, DWI-T2WI set, and combined assessment of DCE and DWI-T2WI were
calculated. RESULTS: Of 169 breast lesions, 48 were benign and 121 were malignant
(89 invasive ductal carcinoma, 24 ductal carcinoma in situ, 4 invasive lobular
carcinoma, 4 mucinous carcinoma). The mean apparent diffusion coefficient (ADC)
of invasive ductal carcinoma (0.92 +/- 0.19 * 10-3 mm2/s) and ductal carcinoma in
situ (1.11 +/- 0.13 * 10-3 mm2/s) was significantly lower than the value seen in
benign lesions (1.36 +/- 0.22 * 10-3 mm2/s). The specificity, positive predictive
value (PPV), and accuracy of DWI-T2WI set and combined assessment of DCE and DWI
T2WI (specificity, 87.5% and 91.7%; PPV, 94.3% and 96.2%; accuracy, Az = 0.876
and 0.922) were significantly higher than those of the DCE-MRI (specificity,
45.8%; PPV, 81.7%; accuracy, Az = 0.854; P < .05). A low ADC value and the
presence of rim enhancement were associated with a higher histologic grade cancer
(P < .05). CONCLUSION: Combining DWI, T2WI, and ADC values provides increased
accuracy for differentiation between benign and malignant lesions, compared with
DCE-MRI. A lower ADC value was associated with a higher histologic grade cancer.
PMID- 29339080
TI - Prostate Cancer Disseminated Tumor Cells are Rarely Detected in the Bone Marrow
of Patients with Localized Disease Undergoing Radical Prostatectomy across
Multiple Rare Cell Detection Platforms.
AB - PURPOSE: Prostate circulating tumor cells escape into peripheral blood and enter
bone marrow as disseminated tumor cells, representing an early step before
conventionally detectable metastasis. It is unclear how frequently this occurs in
localized disease and existing detection methods rely on epithelial markers with
low specificity and sensitivity. We used multiple methodologies of disseminated
tumor cell detection in bone marrow harvested at radical prostatectomy. MATERIALS
AND METHODS: Bone marrow was harvested from 208 clinically localized cases, 16
controls and 5 metastatic cases with peripheral blood obtained from 37 metastatic
cases. Samples were evaluated at 4 centers with 4 distinct platforms using
antibody enrichment with the AdnaTest (Qiagen(r)) or VERSA (versatile exclusion
based rare sample analysis), or whole sample interrogation with the RareCyte
platform (Seattle, Washington) or HD-SCA (high definition single cell assay)
using traditional epithelial markers and prostate specific markers. We
investigated the sensitivity and specificity of these markers by evaluating
expression levels in control and metastatic cases. RESULTS: EpCAM, NKX3.1 and AR
were nonspecifically expressed in controls and in most samples using AdnaTest
with no relation to perioperative variables. Only 1 patient with localized
disease showed positive results for the prostate specific marker PSA. With the
VERSA platform no localized case demonstrated disseminated tumor cells. With the
RareCyte and HD-SCA platforms only a single patient had 1 disseminated tumor
cell. CONCLUSIONS: Evaluation across multiple platforms revealed that epithelial
markers are nonspecific in bone marrow and, thus, not suitable for disseminated
tumor cell detection. Using prostate specific markers disseminated tumor cells
were typically not detected in patients with localized prostate cancer.
PMID- 29339081
TI - Disorder-to-order transitions in the molten globule-like Golgi Reassembly and
Stacking Protein.
AB - BACKGROUND: Golgi Reassembly and Stacking Proteins (GRASPs) are widely spread
among eukaryotic cells (except plants) and are considered as key components in
both the stacking of the Golgi cisternae and its lateral connection. Furthermore,
GRASPs were also proved essential in the unconventional secretion pathway of
several proteins, even though the mechanism remains obscure. It was previously
observed that the GRASP homologue in Cryptococcus neoformans has a molten globule
like behavior in solution. METHODS: We used circular dichroism, synchrotron
radiation circular dichroism and steady-state as well as time-resolved
fluorescence. RESULTS: We report the disorder-to-order transition propensities
for a native molten globule-like protein in the presence of different mimetics of
cell conditions. Changes in the dielectric constant (such as those experienced
close to the membrane surface) seem to be the major factor in inducing multiple
disorder-to-order transitions in GRASP, which shows very distinct behavior when
in conditions that mimic the vicinity of the membrane surface as compared to
those found when free in solution. Other folding factors such as molecular
crowding, counter ions, pH and phosphorylation exhibit lower or no effect on
GRASP secondary structure and/or stability. GENERAL SIGNIFICANCE: To the best of
our knowledge, this is the first study focusing on understanding the disorder-to
order transitions of a molten globule structure without the need of any mild
denaturing condition. A model is also introduced aiming at describing how the
cell could manipulate the GRASP sensitivity to changes in the dielectric constant
during different cell-cycle periods.
PMID- 29339082
TI - Water-mediated interactions enable smooth substrate transport in a bacterial
efflux pump.
AB - BACKGROUND: Efflux pumps of the Resistance-Nodulation-cell Division superfamily
confer multi-drug resistance to Gram-negative bacteria. The most-studied
polyspecific transporter belonging to this class is the inner-membrane trimeric
antiporter AcrB of Escherichia coli. In previous studies, a functional rotation
mechanism was proposed for its functioning, according to which the three monomers
undergo concerted conformational changes facilitating the extrusion of
substrates. However, the molecular determinants and the energetics of this
mechanism still remain unknown, so its feasibility must be proven
mechanistically. METHODS: A computational protocol able to mimic the functional
rotation mechanism in AcrB was developed. By using multi-bias molecular dynamics
simulations we characterized the translocation of the substrate doxorubicin
driven by conformational changes of the protein. In addition, we estimated for
the first time the free energy profile associated to this process. RESULTS: We
provided a molecular view of the process in agreement with experimental data.
Moreover, we showed that the conformational changes occurring in AcrB enable the
formation of a layer of structured waters on the internal surface of the
transport channel. This water layer, in turn, allows for a fairly constant
hydration of the substrate, facilitating its diffusion over a smooth free energy
profile. CONCLUSIONS: Our findings reveal a new molecular mechanism of
polyspecific transport whereby water contributes by screening potentially strong
substrate-protein interactions. GENERAL SIGNIFICANCE: We provided a mechanistic
understanding of a fundamental process related to multi-drug transport. Our
results can help rationalizing the behavior of other polyspecific transporters
and designing compounds avoiding extrusion or inhibitors of efflux pumps.
PMID- 29339083
TI - miRNA15a regulates insulin signal transduction in the retinal vasculature.
AB - We previously reported that tumor necrosis factor alpha (TNFalpha) could inhibit
insulin signal transduction in retinal cells. We recently found that miR15a/16
also reduced TNFalpha in retinal endothelial cells (REC) and in vascular specific
miR15a/16 knockout mice. Since in silico programs suggested that miR15a could
directly bind the insulin receptor, we wanted to determine whether miR15a altered
insulin signal transduction. We used a luciferase-based binding assay to
determine whether miR15a directly bound the insulin receptor. We then used
Western blotting, ELISA, and qPCR to investigate whether miR15a altered insulin
signaling proteins in REC and in both miR15a/16 endothelial cell knockout and
overexpressing mice. We also treated some REC with resveratrol to determine if
resveratrol could increase miR15a expression, since resveratrol is protective to
the diabetic retina. We found that miR15a directly bound the 3'UTR of the insulin
receptor. Treatment with resveratrol increased miR15a expression in REC grown in
high glucose. While total insulin receptor levels were not altered, insulin
signal transduction was reduced in REC grown in high glucose and was restored
with treatment with resveratrol. miR15a knockout mice had reduced insulin
receptor phosphorylation and Akt2 levels, with increased insulin receptor
substrate 1 (IRS-1) phosphorylation on serine 307, a site known to inhibit
insulin signaling. In contrast, overexpression of miR15a increased insulin signal
transduction. Taken together, these data suggest that miR15a binds the insulin
receptor and indirectly regulates insulin receptor actions. It also offers an
additional mechanism by which resveratrol is protective to the diabetic retina.
PMID- 29339084
TI - miR-613 inhibits cell migration and invasion by downregulating Daam1 in triple
negative breast cancer.
AB - Dishevelled-associated activator of morphogenesis 1 (Daam1) is a formin protein
and participates in regulating cell migration of triple-negative breast cancer
(TNBC) cells. The specific miRNA targeting Daam1 and mediating cell migration and
invasion remains obscure. This experiment investigated the suppressive role of
miR-613 in TNBC cells. The luciferase activity of Daam1 3'-untranslated region
(3'-UTR) based reporters constructed in HEK-293T and MCF-7 cells suggested that
Daam1 was the target gene of miR-613. Overexpressed miR-613 reduced the protein
level of Daam1, weakened RhoA activity, and retarded the cell migration, cell
invasion and colony formation of TNBC cells. Overexpression of Daam1 or RhoA
rescued cell migration and invasion in miR-613-overexpressed TNBC cells, but
failed to reverse colony formation. MiR-613 was significantly downregulated in
breast cancer tissues compared with that in adjacent normal tissues. This
downregulation in TNBC tissues and lymphnode metastatic breast cancer tissues was
more obvious than that in non-TNBC tissues and non-metastatic cancer tissues,
respectively. MiR-613 weakens the resistance of TNBC cells against paclitaxel
rather than adriamycin, cyclophosphamide, docetaxel, and kaempferol. Taken
together, miR-613 is involved in cell migration and invasion of TNBC cells via
targeting Daam1/RhoA signaling pathway.
PMID- 29339085
TI - Wnt5a mediates chronic post-thoracotomy pain by regulating non-canonical
pathways, nerve regeneration, and inflammation in rats.
AB - As well-characterized ligands involved in neurogenesis, Wnts are emerging as
promising targets in pain pathogenesis. Our previous pilot study showed that
intrathecal inhibition of Wnt5a, but not Wnts, relieves chronic post-thoracotomy
pain (CPTP) in rats. In the present study, we aimed to further explore the
regulatory mechanism of Wnt5a in CPTP development. Increased protein levels of
Wnt5a, transmembrane receptor Ror2, and activated non-canonical Wnt pathway
members were found in the thoracic dorsal root ganglions from postoperative day
(POD) 7 to POD 21. However, the levels of canonical Wnt pathway members showed no
change by reverse transcriptase-PCR. In addition, elevated nerve regeneration,
activated pro-inflammatory factors, and glial cells were detected from POD 7 to
POD 21. Furthermore, intrathecal Wnt5a blockade during the early phase (POD 0 to
POD 9) significantly increased the pain threshold, and intervention in the late
phase (POD 14 to POD 16) alleviated pain; however, the analgesic response was not
as effective as that in the early phase. Additionally, early but not late Wnt5a
blockade significantly reversed CPTP-induced activation of the non-canonical Wnt
pathways, nerve regeneration, and inflammation. In contrast, a Wnt5a agonist
decreased the pain threshold in both naive and painless rats. These results
suggest that Wnt5a promotes the development of CPTP by activating non-canonical
Wnt pathways, nerve regeneration, and inflammation. Therapeutic intervention by
targeting Wnt5a may represent an effective strategy for preventing and treating
CPTP.
PMID- 29339086
TI - The IL-6/STAT3 pathway regulates adhesion molecules and cytoskeleton of
endothelial cells in thromboangiitis obliterans.
AB - Thromboangiitis obliterans (TAO) (also known as Buerger's disease) is an
inflammatory vascular disease that predominantly affects small- and medium-sized
blood vessels of extremities. Endothelial cells play critical roles in the
initiation and progression of this disease, but the underlying mechanisms remain
unclear. In the present study, we demonstrate that patients with TAO had
significantly higher levels of interleukin-6 (IL-6), soluble intercellular
adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1
(sVCAM-1) in their plasmas, and the involved arterial tissues expressed higher
levels of phosphorylated signal transducer and activator of transcription 3 (p
STAT3), ICAM-1 and VCAM-1. In exploring the molecular mechanisms with human
aortic endothelial cells (HAECs), we found that recombinant IL-6 activated the
STAT3 pathway, leading to the upregulation and overproduction of ICAM-1 and VCAM
1. RhoA (Ras homolog family member A), eNOS (endothelial nitric oxide synthase)
and MMP-9 (matrix metalloproteinase-9) participated in this cellular signaling,
and their interaction regulated the expression of ICAM-1 and VCAM-1. The
activated STAT3 pathway by IL-6 also modulated the cytoskeleton of HAECs by
regulating phosphorylation of focal adhesion kinase (FAK) and acetylation of
alpha-tubulin through interplaying with RhoA. In summary, the present results
indicate that activation of the IL-6/STAT3 pathway contributes to the
pathogenesis of TAO by regulating cellular adhesion molecules and cytoskeleton of
vascular endothelial cells, suggesting that targeting this pathway may provide a
potential approach for the management of TAO.
PMID- 29339087
TI - Erratum to: "Spasmodic torticollis after orthognathic surgery" [J. Stomatol. Oral
Maxillofac. Surg. 118 (2017) 393-6].
PMID- 29339088
TI - Retinal neuronal cell loss prevents abnormal retinal vascular growth in a rat
model of retinopathy of prematurity.
AB - A short-term blockade of the vascular endothelial growth factor (VEGF)-mediated
pathway in neonatal rats results in formation of severe retinopathy of
prematurity (ROP)-like retinal blood vessels. The present study aimed to examine
the role of retinal neurons in the formation of abnormal retinal blood vessels.
Newborn rats were treated subcutaneously with the VEGF receptor tyrosine kinase
inhibitor, KRN633 (10 mg/kg), or its vehicle (0.5% methylcellulose in water) on
postnatal day (P) 7 and P8. To induce excitotoxic loss of retinal neurons, N
methyl-D-aspartic acid (NMDA) was injected into the vitreous chamber of the eye
on P9. Changes in retinal morphology, blood vessels, and proliferative status of
vascular cells were evaluated on P11 and P14. The number of cells in the ganglion
cell layer and the thickness of the inner plexiform layer and inner nuclear layer
were significantly decreased 2 days (P11) after NMDA treatment. The pattern and
degree of NMDA-induced changes in retinal morphology were similar between vehicle
treated (control) and KRN633-treated (ROP) rats. In ROP rats, increases in the
density of capillaries, the tortuosity index of arteries, and the proliferating
vascular cells were observed on P14. The expansion of the endothelial cell
network was prevented, and the capillary density and the number of proliferating
cells were reduced in NMDA-treated retinas of both control and ROP rats.
Following NMDA-induced neuronal cell loss, no ROP-like blood vessels were
observed in the retinas. These results suggest that retinal neurons play an
important role in the formation of normal and ROP-like retinal blood vessels.
PMID- 29339089
TI - Concentration gradient of noradrenaline from the periphery to the centre of the
cornea - A clue to its origin.
AB - We set out to demonstrate that the major source of corneal catecholamines is its
neuronal release from intrinsic sympathetic nerves rather than circulating or non
neuronal local production. Three concentric segments (central, intermediate,
peripheral) were obtained by double trephination (9.5-7.25 mm) performed on
corneas harvested from 3 to 4 month old rabbits and human corneas rejected for
transplantation, along with aqueous humour, full iris tissue and blood samples.
Endogenous catecholamines were quantified by high pressure liquid chromatography
with electrochemical detection (HPLC-ED), and comparison with the uptake of radio
labelled noradrenaline (3H-NA) before and after incubation with cocaine was
performed. Results are means +/- SEM. Ratios between enzymatic end products and
their substrates were calculated. ANOVA was used for statistical analysis.
Catecholamine levels were found to be about one log unit lower in the human
cornea than in the rabbit cornea. In the rabbit, dopamine (DA), noradrenaline
(NA) and adrenaline (AD) were identified by HPLC-ED in all corneal segments,
whilst in the human cornea NA was identified only in the intermediate and
peripheral corneal segments, and no AD was found. In the iris and aqueous humour
only DA and NA were present. A concentration gradient for NA decreasing from the
periphery to the centre of the cornea was identified in both species (NA/DA ratio
higher than 1 in the periphery; low AD/NA ratio in all corneal segments), but not
for DA or AD. After incubation with 3H-NA all corneal segments and iris tissue
showed loading with the aforementioned gradient being reproduced, and a decrease
in 3H-NA loading after cocaine was significant only in the peripheral corneal
segment and in the iris of both species. Reduction in 3H-NA loading after
incubation with cocaine shows that NA in the cornea is mostly of neuronal origin
and demonstrates the presence of functional sympathetic nerves (also expectedly
found in the iris); the existence of a gradient both for 3H-NA loading and
loading reduction after cocaine points to a higher density of fibres in the
peripheral cornea.
PMID- 29339090
TI - Patched 1 Expression Correlates with Biochemical Relapse in High-Risk Prostate
Cancer Patients.
AB - There is an unmet clinical need for adequate biomarkers to aid risk
stratification and management of prostate cancer (PCa) patients. Even within the
high-risk PCa category, not all patients will invariably have a poor prognosis,
and improved stratification of this heterogeneous group is needed. In this
context, components of the hedgehog (Hh) pathway may have promise as biomarkers,
because the available evidence suggests increased Hh pathway activity may confer
a poorer outcome in advanced and castrate-resistant PCa. In this study, potential
associations between Hh pathway protein expression and clinicopathological
factors, including time to biochemical recurrence (BCR), were investigated using
a tissue microarray constructed from benign and malignant prostate samples from
75 predominantly high-risk PCa patients who underwent radical prostatectomy. Hh
signaling activity was found to differ between benign and malignant prostate
tissue, with a greater amount of active Hh signaling present in malignant than
benign prostate epithelium. High expression of Patched 1 in malignant prostate
epithelium was found to be an independent predictor of BCR in high-risk PCa
patients. Glioma-associated oncogene 1 may potentially represent a clinically
useful biomarker of an aggressive tumor phenotype. Evaluation of Hh signaling
activity in PCa patients may be useful for risk stratification, and epithelial
Patched 1 expression, in particular, may be a prognostic marker for BCR in high
risk PCa patients.
PMID- 29339092
TI - Structural and biochemical analyses reveal ubiquitin C-terminal hydrolase-L1 as a
specific client of the peroxiredoxin II chaperone.
AB - Peroxiredoxins (Prxs) play dual roles as both thiol-peroxidases and molecular
chaperones. Peroxidase activity enables various intracellular functions, however,
the physiological roles of Prxs as chaperones are not well established. To study
the chaperoning function of Prx, we previously sought to identify heat-induced
Prx-binding proteins as the clients of a Prx chaperone. By using His-tagged Prx I
as a bait, we separated ubiquitin C-terminal hydrolase-L1 (UCH-L1) as a heat
induced Prx I binding protein from rat brain crude extracts. Protein complex
immunoprecipitation with HeLa cell lysates revealed that both Prx I and Prx II
interact with UCH-L1. However, Prx II interacted considerably more favorably with
UCH-L1 than Prx I. Prx II exhibited more effective molecular chaperone activity
than Prx I when UCH-L1 was the client. Prx II interacted with UCH-L1 through its
C-terminal region to protect UCH-L1 from thermal or oxidative inactivation. We
found that chaperoning via interaction through C-terminal region (specific-client
chaperoning) is more efficient than that involving oligomeric structural change
(general-client chaperoning). Prx II binds either thermally or oxidatively
unfolding early intermediates of specific clients and thereby shifted the
equilibrium towards their native state. We conclude that this chaperoning
mechanism provides a very effective and selective chaperoning activity.
PMID- 29339093
TI - The proteoglycan biglycan mediates inflammatory response by activating TLR-4 in
human chondrocytes: Inhibition by specific siRNA and high polymerized Hyaluronan.
AB - Cartilage degeneration are hallmarks of wear, tear, mechanical and inflammatory
damage of the joint cartilage. Tissue degradation as well as compromising the
integrity and function of the organ, produces different intermediates, directly
able to stimulate further inflammatory effect, therefore, amplifying the
inflammation response. Biglycan is a soluble component of the extracellular
matrix that is released during tissue injury. It has been reported that released
biglycan is an endogenous ligand for TLR-2/4 in some cell type. We studied the
role of biglycan in an experimental model of biglycan-induced inflammatory
response in human chondrocytes and the effect of high polymerized HA on reducing
its activity. Exposition of chondrocytes to LPS generated cell injury, including
high levels of biglycan. Chondrocyte treatment with biglycan produces a high mRNA
expression of several detrimental inflammation mediators such as IL-1beta, IL-6,
MMP-13, and IL-17, as well as NF-kB and TLR-4 activation. Administration of high
polymerized HA to chondrocytes exposed to biglycan was able to attenuate the
inflammatory response by decreasing the expression of the inflammatory mediators.
Involvement of the TLR-4 in the mediation of the biglycan action was confirmed
using a specific silent agent (siRNA). Taken together, these data could be used
to develop new anti-inflammatory approaches.
PMID- 29339095
TI - Patterning the gastrointestinal epithelium to confer regional-specific functions.
AB - The gastrointestinal (GI) tract, in simplest terms, can be described as an
epithelial-lined muscular tube extending along the cephalocaudal axis from the
oral cavity to the anus. Although the general architecture of the GI tract organs
is conserved from end to end, the presence of different epithelial tissue
structures and unique epithelial cell types within each organ enables each to
perform the distinct digestive functions required for efficient nutrient
assimilation. Spatiotemporal regulation of signaling pathways and downstream
transcription factors controls GI epithelial morphogenesis during development to
confer essential regional-specific epithelial structures and functions. Here, we
discuss the fundamental functions of each GI tract organ and summarize the
diversity of epithelial structures present along the cephalocaudal axis of the GI
tract. Next, we discuss findings, primarily from genetic mouse models, that have
defined the roles of key transcription factors during epithelial morphogenesis,
including p63, SOX2, SOX15, GATA4, GATA6, HNF4A, and HNF4G. Additionally, we
examine how the Hedgehog, WNT, and BMP signaling pathways contribute to defining
unique epithelial features along the cephalocaudal axis of the GI tract. Lastly,
we examine the molecular mechanisms controlling regionalized cytodifferentiation
of organ-specific epithelial cell types within the GI tract, concentrating on the
stomach and small intestine. The delineation of GI epithelial patterning
mechanisms in mice has provided fundamental knowledge to guide the development
and refinement of three-dimensional GI organotypic culture models such as those
derived from directed differentiation of human pluripotent stem cells and those
derived directly from human tissue samples. Continued examination of these
pathways will undoubtedly provide vital insights into the mechanisms of GI
development and disease and may afford new avenues for innovative tissue
engineering and personalized medicine approaches to treating GI diseases.
PMID- 29339096
TI - A new option for remission induction in acute myeloid leukaemia.
PMID- 29339091
TI - An energetic view of stress: Focus on mitochondria.
AB - Energy is required to sustain life and enable stress adaptation. At the cellular
level, energy is largely derived from mitochondria - unique multifunctional
organelles with their own genome. Four main elements connect mitochondria to
stress: (1) Energy is required at the molecular, (epi)genetic, cellular,
organellar, and systemic levels to sustain components of stress responses; (2)
Glucocorticoids and other steroid hormones are produced and metabolized by
mitochondria; (3) Reciprocally, mitochondria respond to neuroendocrine and
metabolic stress mediators; and (4) Experimentally manipulating mitochondrial
functions alters physiological and behavioral responses to psychological stress.
Thus, mitochondria are endocrine organelles that provide both the energy and
signals that enable and direct stress adaptation. Neural circuits regulating
social behavior - as well as psychopathological processes - are also influenced
by mitochondrial energetics. An integrative view of stress as an energy-driven
process opens new opportunities to study mechanisms of adaptation and regulation
across the lifespan.
PMID- 29339097
TI - Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in
elderly patients with previously untreated acute myeloid leukaemia: a non
randomised, open-label, phase 1b study.
AB - BACKGROUND: Elderly patients (aged >=65 years) with acute myeloid leukaemia have
poor outcomes and no effective standard-of-care therapy exists. Treatment with
hypomethylating agents such as azacitidine and decitabine is common, but
responses are modest and typically short-lived. The oral anti-apoptotic B-cell
lymphoma 2 protein inhibitor, venetoclax, has shown promising single-agent
activity in patients with relapsed or refractory acute myeloid leukaemia and
preclinical data suggested synergy between hypomethylating agents and venetoclax,
which led to this combination phase 1b study. METHODS: Previously untreated
patients aged 65 years and over with acute myeloid leukaemia who were ineligible
for standard induction therapy were enrolled into this non-randomised, open
label, phase 1b study. Patients were required to have an Eastern Cooperative
Oncology Group performance status of 0-2 and either intermediate-risk or poor
risk cytogenetics. Patients were enrolled into one of three groups for the dose
escalation phase of this study: group A (venetoclax and intravenous decitabine 20
mg/m2 [days 1-5 of each 28-day cycle]), group B (venetoclax and subcutaneous or
intravenous azacitidine 75 mg/m2 [days 1-7 of each 28-day cycle]), and group C (a
venetoclax and decitabine substudy with the oral CYP3A inhibitor posaconazole,
300 mg twice on cycle 1, day 21, and 300 mg once daily from cycle 1, days 22-28,
to assess its effect on venetoclax pharmacokinetics). Dose escalation followed a
standard 3 + 3 design with at least three evaluable patients enrolled per cohort;
daily target doses of venetoclax for groups A and B were 400 mg (cohort 1), 800
mg (cohorts 2 and 3), and 1200 mg (cohort 4), and 400 mg for group C. The primary
endpoints were the safety and pharmacokinetics of venetoclax plus decitabine or
azacitidine, and to determine the maximum tolerated dose and recommended phase 2
dose. Secondary endpoints included the preliminary anti-leukaemic activity of
venetoclax with decitabine or azacitidine through the analysis of overall
response, duration of response, and overall survival. We analysed safety,
pharmacokinetics, and anti-leukaemic activity in all patients who received one or
more venetoclax doses. The expansion phase of the study is ongoing but is closed
to accrual. This trial is registered with ClinicalTrials.gov, number NCT02203773.
FINDINGS: 57 patients were enrolled in the study. 23 patients in group A and 22
patients in group B were enrolled between Nov 19, 2014, and Dec 15, 2015, and 12
patients in group C were enrolled between June 14, 2015, and Jan 16, 2016. As of
data cutoff on June 15, 2016, the most common grade 3-4 treatment-emergent
adverse events were thrombocytopenia (27 [47%] of 57 patients; nine in group A,
13 in group B, and five in group C), febrile neutropenia (24 [42%] of 57; 11 in
group A, ten in group B, and three in group C), and neutropenia (23 [40%] of 57;
12 in group A, eight in group B, and three in group C). The most common serious
treatment-emergent adverse event in groups A and B was febrile neutropenia (seven
[30%] of 23 patients vs seven [32%] of 22), whereas in group C it was lung
infection (four [33%] of 12 patients). 49 (86%) of 57 patients had treatment
related adverse events; the most common in groups A and B included nausea (12
[52%] patients vs seven [32%] patients), fatigue (six [26%] patients vs seven
[32%]), and decreased neutrophil count (six [26%] patients vs six [27%]), whereas
in group C the most common were nausea (seven [58%] of 12 patients), leucopenia
(six [50%]), vomiting (five [42%]), and decreased platelet count (five [42%]).
The maximum tolerated dose was not reached. The recommended phase 2 dose was 400
mg once a day or 800 mg with an interrupted dosing schedule (safety expansion).
In total, four (7%) of 57 patients had died within 30 days of the first
venetoclax dose caused by sepsis (group B), bacteraemia (group A), lung infection
(group C), and respiratory failure (group A). Tumour lysis syndrome was not
observed. Decitabine and azacitidine did not substantially affect venetoclax
exposures. Overall, 35 (61%; 95% CI 47.6-74.0) of 57 patients achieved complete
remission or complete remission with incomplete marrow recovery. In groups A and
B, 27 (60%; 95% CI 44.3-74.3) of 45 patients had complete remission or complete
remission with incomplete marrow recovery. INTERPRETATION: Venetoclax plus
hypomethylating agent therapy seems to be a novel, well-tolerated regimen with
promising activity in this underserved patient population. Evaluation of
expansion cohorts is ongoing at 400 mg and 800 mg doses using both
hypomethylating agent combinations. FUNDING: AbbVie and Genentech.
PMID- 29339098
TI - Vitamin D and Nonalcoholic Fatty Liver Disease: Bi-directional Mendelian
Randomization Analysis.
AB - BACKGROUND: Vitamin D deficiency is associated with nonalcoholic fatty liver
disease (NAFLD) in many cross-sectional studies. However, the causality between
them has not been established. We used bi-directional mendelian randomization
(MR) analysis to explore the causal relationship between 25-hydroxyvitamin D
[25(OH)D] and NAFLD. METHODS: 9182 participants were included from a survey in
East China from 2014 to 2016. We calculated weighted genetic risk scores (GRS)
for 25(OH)D concentration and NAFLD based on 25(OH)D-related and NAFLD-related
single nucleotide polymorphisms. Presence of liver steatosis was assessed using
ultrasound. Instrumental variable was used to measure the causal relationship
between them. RESULTS: An SD increase in the 25(OH)D GRS was significantly
associated with 25(OH)D (beta 1.29, 95%CI -1.54, -1.04, P<0.05) but not with
NAFLD (OR 0.97, 95%CI 0.92, 1.01). An SD increase in NAFLD GRS was also strongly
associated with NAFLD (OR 1.09, 95%CI 1.04, 1.15, P<0.05) but not with 25(OH)D
(beta -0.15, 95%CI -0.41, 0.10). Using an instrumental variable estimator, no
associations were found for genetically instrumented 25(OH)D with NAFLD and for
genetically instrumented NAFLD with 25(OH)D. CONCLUSION: Our results support the
conclusion that there is no causal association between vitamin D and NAFLD using
a bi-directional MR approach in a Chinese population.
PMID- 29339099
TI - Intestinal Adenovirus Shedding Before Allogeneic Stem Cell Transplantation Is a
Risk Factor for Invasive Infection Post-transplant.
AB - Human adenoviruses (HAdV) are a major cause of morbidity and mortality in
pediatric human stem cell transplant (HSCT) recipients. Our previous studies
identified the gastrointestinal tract as a site of HAdV persistence, but the role
of intestinal virus shedding pre-transplant for the risk of ensuing invasive
infection has not been entirely elucidated. Molecular HAdV monitoring of serial
stool samples using RQ-PCR was performed in 304 children undergoing allogeneic
HSCT. Analysis of stool and peripheral blood specimens was performed pre
transplant and at short intervals until day 100 post-HSCT. The virus was detected
in the stool of 129 patients (42%), and 42 tested positive already before HSCT.
The patients displaying HAdV shedding pre-transplant showed a significantly
earlier increase of intestinal HAdV levels above the critical threshold
associated with high risk of invasive infection (p<0.01). In this subset of
patients, the occurrence of invasive infection characterized by viremia was
significantly higher than in patients without HAdV shedding before HSCT (33% vs
7%; p<0.0001). The data demonstrate that intestinal HAdV shedding before HSCT
confers a greatly increased risk for invasive infection and disseminated disease
post-transplant, and highlights the need for timely HAdV monitoring and pre
emptive therapeutic considerations in HSCT recipients.
PMID- 29339100
TI - Genetic Variation in the Dopamine System Influences Intervention Outcome in
Children with Cerebral Palsy.
AB - BACKGROUND: There is large variation in treatment responses in children with
cerebral palsy. Experimental and clinical results suggest that dopamine
neurotransmission and brain-derived neurotrophic factor (BDNF) signalling are
involved in motor learning and plasticity, which are key factors in modern
habilitation success. We examined whether naturally occurring variations in
dopamine and BDNF genes influenced the treatment outcomes. METHODS: Thirty-three
children (18-60months of age) with spastic unilateral cerebral palsy were
enrolled in the study. Each child had participated in a training programme
consisting of active training of the involved hand for 2h every day during a 2
month training period. The training outcome was measured using Assisting Hand
Assessment before and after the training period. Saliva was collected for
genotyping of COMT, DAT, DRD1, DRD2, DRD3, and BDNF. Regression analyses were
used to examine associations between genetic variation and training outcome.
FINDINGS: There was a statistically significant association between variation in
dopamine genes and treatment outcome. Children with a high polygenic dopamine
gene score including polymorphisms of five dopamine genes (COMT, DAT, DRD1, DRD2,
and DRD3), and reflecting higher endogenous dopaminergic neurotransmission, had
the greatest functional outcome gains after intervention. INTERPRETATION:
Naturally occurring genetic variation in the dopamine system can influence
treatment outcomes in children with cerebral palsy. A polygenic dopamine score
might be valid for treatment outcome prediction and for designing individually
tailored interventions for children with cerebral palsy.
PMID- 29339101
TI - Atherogenic diet induced lipid accumulation induced NFkappaB level in heart,
liver and brain of Wistar rat and diosgenin as an anti-inflammatory agent.
AB - Atherogenic Diet (AD) was given to rats to understand the key role of
inflammatory mediators in atherosclerotic lesion formation, as a serendipitous
study, the diet induced inflammatory mediators in liver and brain, whereas
pancreas, kidney and spleen were not affected. The efficacy of diosgenin in
ameliorating atherosclerotic progression in heart and suppression of inflammatory
mediators in liver and brain of Wistar rat fed on AD diet was investigated.
Atherogenic diet triggered inflammatory mediators in heart, liver and brain by
upregulating TNF-alpha, COX-2 and NFkBp65 which are the inflammatory hub, played
a key role in pathophysiologic conditions. Endothelial dysfunction, liver tissue
with prominent steatosis and the stress evoked in the brain by the atherogenic
diet triggered these inflammatory mediators. TNF-alpha and COX-2 expression was
upregulated and its elevation was associated with NFkBp65 activation in heart,
liver and brain of atherogenic diet induced rat. Diosgenin downregulated these
inflammatory mediators, thereby prevented the atherosclerotic disease progression
and concomitant suppression of inflammatory mediators in liver and brain.
PMID- 29339102
TI - Spirulina ameliorates methotrexate hepatotoxicity via antioxidant, immune
stimulation, and proinflammatory cytokines and apoptotic proteins modulation.
AB - AIMS: Methotrexate (MTX) is an efficient cytotoxic drug used against various
carcinogenic, inflammatory and autoimmune diseases; however, the hepatotoxicity
of MTX limits its use. Therefore, the present study aimed to evaluate the
potential hepatoprotective and immune-stimulant effect of Spirulina platensis
(SP) against MTX acute toxicity. MAIN METHODS: Thirty-two male Wistar rats were
randomly allocated into the following four groups (n = 8): control, SP (500 mg/kg
bwt, oral gavage daily for 21 days), MTX (20 mg/kg bwt, single ip injection), and
MTX+SP. Hepatic and splenic histoarchitecture, leukocyte counts and serum
immunoglobulins were evaluated. Hepatic oxidant/antioxidant status,
proinflammatory cytokines (tumor necrosis factor-alpha, and interleukin 6), and
pro-apoptotic proteins (caspase 3 and Bax) immunoexpression were assessed. KEY
FINDINGS: MTX induced extensive hepatic necrosis and vacuolation, and sever
lymphoid depletion in splenic white pulp with increased levels of serum
transaminases, lactate dehydrogenase, and hepatic malondialdehyde, tumor necrosis
factor-alpha and interleukin 6; and number of caspase 3- and Bax-positive
hepatocytes. A significant decrease in leukocyte counts, serum immunoglobulins
(IgA, IgM and IgG) level, and hepatic antioxidant enzymes (GSH, GPx, SOD, and
CAT) was also detected. Pretreatment with SP resulted in significant improvements
in hepatic and splenic histologic architecture, as well as restoring liver
enzymes and reduction of lipid peroxidation product, proinflammatory cytokines,
and caspase 3 and Bax immunoexpression. Additionally, a significant increase in
antioxidant enzymes, serum immunoglobulins, and total leukocyte counts was
demonstrated. SIGNIFICANCE: SP possesses promising antioxidant, anti
inflammatory, anti-apoptotic and immune stimulatory properties against MTX
induced hepatotoxicity and immunosuppression.
PMID- 29339103
TI - Comparative review of adult midbrain and striatum neurogenesis with classical
neurogenesis.
AB - Parkinson's Disease (PD) motor symptoms are caused by loss of dopamine (DA)
neurons in the substantia nigra pars compacta (SNc) of the midbrain. Dopamine
cell replacement therapy (DA CRT), either by cell transplantation or endogenous
repair, has been a potential treatment to replace dead cells and improve PD motor
symptoms. Adult midbrain and striatum have been studied for many years to find
evidence of neurogenesis. Although the literature is controversial, recent
research has revived the possibility of neurogenesis here. This paper aims to
review the process of neurogenesis (by focusing on gene expression patterns) in
the adult midbrain/striatum and compare it with classical neurogenesis that
occurs in developing midbrain, Sub Ventricular Zone (SVZ) and Sub Granular Zone
(SGZ) of the adult brain.
PMID- 29339104
TI - Region-specific innate antiviral responses of the human epididymis.
AB - Viral infections of the epididymis are associated with epididymitis, which
damages the epithelium and impairs fertility. We showed previously that innate
immune response genes were differentially expressed in the corpus and cauda
region of the human epididymis in comparison to the caput. Here we investigate
the antiviral defense response mechanisms of human epididymis epithelial (HEE)
cells. Toll-like receptor (TLR) 3 and retinoic acid-inducible gene I (RIG-I)-like
receptors (RLRs) are enriched in HEE cells from the corpus and cauda region.
These HEE cells show an enhanced response to antiviral ligands (poly(I:C) and HSV
60), as shown by increased IFN-beta mRNA expression and IFN-beta secretion.
Nuclear translocation of phosphorylated p65 occurs after poly(I:C) exposure. In
addition, paired box 2 (PAX2), which was implicated in regulating antiviral
response pathways, is required for basal expression of the DNA sensor, Z-DNA
binding protein (ZBP1) and type I interferon, in caput but not in cauda cells.
PMID- 29339105
TI - Effects of thymol on amyloid-beta-induced impairments in hippocampal synaptic
plasticity in rats fed a high-fat diet.
AB - Obesity and a high-fat diet (HFD) are known to increase the incidence of
Alzheimer's disease (AD). Oxidative stress, a major risk factor for AD, is
increased with HFD consumption. Thymol (Thy) has antioxidant properties.
Therefore, in the present study, we examined the protective and therapeutic
effects of Thy on amyloid-beta (Abeta)-induced impairments in the hippocampal
synaptic plasticity of HFD-fed rats. In this study, 72 adult male Wistar rats
were randomly assigned to 9 groups (n = 8 rats/group): Group 1 (control; standard
diet); Group 2: Control + phosphate-buffered saline (PBS) + Oil (Thy vehicle);
Group 3 (HFD + PBS); Group 4: (HFD + Abeta); Group 5: Control + PBS + Thy; Group
6: (HFD + Abeta + Oil); Group 7: Control + Abeta + Thy; Group 8: HFD + PBS + Thy;
Group 9: (HFD + Abeta + Thy). After stereotaxic surgery, the field potentials
were recorded after the implantation of the recording and stimulating electrodes
in the dentate gyrus (DG) and perforant pathway, respectively. Following high
frequency stimulation, the long-term potentiation (LTP) of the population spike
(PS) amplitude and the slope of the excitatory postsynaptic potentials (EPSPs)
were measured in the DG. The HFD rats that received Abeta exhibited a significant
decrease in their EPSP slope and PS amplitude as compared to the control group.
In contrast, Thy administration in the HFD + Abeta rats reduced the decrease in
the EPSP slope and PS amplitude. Thy decreased the Abeta-induced LTP impairments
in HFD rats. The HFD significantly increased serum malondialdehyde levels and
decreased total antioxidant capacity and total glutathione levels; whereas, Thy
supplementation significantly reversed these parameters. Therefore, these results
suggest that Thy, a natural antioxidant, can be therapeutic against high risk
factors for AD, such as HFD.
PMID- 29339106
TI - Safinamide: a new hope for Parkinson's disease?
AB - The loss of dopaminergic neurons (DAn) and reduced dopamine (DA) production
underlies the reasoning behind the gold standard treatment for Parkinson's
disease (PD) using levodopa (L-DOPA). Recently licensed by the European Medicine
Agency (EMA) and US Food and Drug Administration (FDA), safinamide [a monoamine
oxidase B (MOA-B) inhibitor] is an alternative to L-DOPA; as we discuss here, it
enhances dopaminergic transmission with decreased secondary effects compared with
L-DOPA. In addition, nondopaminergic actions (neuroprotective effects) have been
reported, with safinamide inhibiting glutamate release and sodium/calcium
channels, reducing the excitotoxic input to dopaminergic neuronal death. Effects
of safinamide have been correlated with the amelioration of non-motor symptoms
(NMS), although these remain under discussion. Overall, safinamide can be
considered to have potential antidyskinetic and neuroprotective effects and
future trials and/or studies should be performed to provide further evidence for
its potential as an anti-PD drug.
PMID- 29339107
TI - Influenza A virus polymerase: an attractive target for next-generation anti
influenza therapeutics.
AB - The influenza RNA-dependent RNA polymerase (RdRP) is conserved among different
types of influenza virus, playing an important part in transcription and
replication. In this regard, influenza RdRP is an attractive target for novel
anti-influenza drug discovery. Herein, we will introduce the structural and
functional information of influenza polymerase; and an overview of inhibitors
targeting the PA endonuclease and PB2 cap-binding site is provided, along with
the approaches utilized for identification of these inhibitors. The protein
protein interactions (PPIs) of the three polymerase subunits: PA, PB1 and PB2,
are described based on the published crystal structures, and inhibitors targeting
the PA-PB1 interaction are introduced briefly.
PMID- 29339108
TI - Phenotype in girls and women with Turner syndrome: Association between dysmorphic
features, karyotype and cardio-aortic malformations.
AB - INTRODUCTION: Turner syndrome (TS) is a genetic disorder characterized by the
(partial) absence or a structural aberration of the second sex chromosome and is
associated with a variety of phenotypes with specific physical features and
cardio-aortic malformations. The objective of this study was to gain a better
insight into the differences in dysmorphic features between girls and women with
TS and to explore the association between these features, karyotype and cardio
aortic malformations. METHODS: This prospective study investigated 14 dysmorphic
features of TS girls and women using a checklist. Three major phenotypic patterns
were recognized (severe phenotype, lymphatic phenotype and skeletal phenotype).
Patient data including karyotype and cardio-aortic malformations (bicuspid aortic
valve (BAV) and aortic coarctation (COA)) were collected. Associations between
the prevalence of dysmorphic features, karyotype and cardio-aortic malformations
were analysed using chi2-test and odds ratios. RESULTS: A total of 202 patients
(84 girls and 118 women) were analysed prospectively. Differences in prevalence
of dysmorphic features were found between girls and women. A strong association
was found between monosomy 45,X and the phenotypic patterns. Furthermore, an
association was found between COA and lymphatic phenotype, but no association was
found between karyotype and cardio-aortic malformations. CONCLUSION: This study
uncovered a difference in dysmorphic features between girls and women. Monosomy
45,X is associated with a more severe phenotype, lymphatic phenotype and skeletal
phenotype. All patients with TS should be screened for cardio-aortic
malformations, because in contrast to previous reports, karyotype and cardio
aortic malformations showed no significant association.
PMID- 29339110
TI - In vitro anti-diabetic effect of flavonoids and pheophytins from Allophylus
cominia Sw. on the glucose uptake assays by HepG2, L6, 3T3-L1 and fat
accumulation in 3T3-L1 adipocytes.
AB - BACKGROUND AND PURPOSE: Based on ethno-botanical information collected from
diabetic patients in Cuba and firstly reported inhibition of PTP1B and DPPIV
enzymes activities, Allophylus cominia (A. cominia) was identified as possible
source of new drugs that could be used for the treatment of type 2 diabetes
mellitus (T2-DM). EXPERIMENTAL APPROACH: in this study, the activity of the
characterised extracts from A. cominia was tested on the glucose uptake using
HepG2 and L6 cells, 3T3-L1 fibroblasts and adipocytes as well as their effect on
the fat accumulation using 3T3-L1 adipocytes. KEY RESULTS: on 2-NBDG glucose
uptake assay using HepG2 and L6 cells, extracts from A. cominia enhanced insulin
activity by increasing glucose uptake. On HepG2 cells Insulin EC50 of 93 +/- 21nM
decreased to 13 +/- 2nM in the presence of the flavonoids mixture from A.cominia.
In L6 cells, insulin also produced a concentration-dependent increase with an
EC50 of 28.6 +/- 0.7nM; EC50 decreased to 0.08 +/- 0.02nM and 5 +/- 0.9nM in the
presence of 100MUg/ml of flavonoids and pheophytins mixtures, respectively. In
3T3-L1 fibroblasts, insulin had an EC50 of >1000nM that decreased to 38 +/- 4nM
in the presence of the flavonoids extract. However, in adipocytes, insulin
produced a significant concentration-dependent increase and an EC50 of 30 +/- 8nM
was a further confirmation of the insulin responsiveness of the adipocytes to the
insulin. At 100ug/ml, flavonoids and pheophytins extracts decreased fat
accumulation in 3T3-L1 adipocytes by two folds in comparison to the control
differentiated cells (p < 0.05). The crude extract of A. cominia did not show any
enhancement of 2-NBDG uptake by 3T3-L1 adipocytes in the presence or absence of
100nM insulin. In addition, in fully differentiated adipocytes, both extracts
produced significant decrease in lipid droplets in the cells and no lipid
accumulation were seen after withdrawal of the extracts from the cell growth
medium. However, there was no effect of both extracts on total protein
concentration in cells as well as on Glut-4 transporters. CONCLUSIONS AND
IMPLICATIONS: the pharmacological effects of the extracts from A. cominia
observed in experimental diabetic models were shown in this study. A. cominia is
potentially a new candidate for the treatment and management of T2-DM.
PMID- 29339109
TI - Bitter gourd reduces elevated fasting plasma glucose levels in an intervention
study among prediabetics in Tanzania.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Impaired glucose tolerance and diabetes mellitus
have become major health issues even in non-industrialized countries. As access
to clinical management is often poor, dietary interventions and alternative
medicines are required. For bitter gourd, Momordica charantia L., antidiabetic
properties have been claimed. AIM OF THE STUDY: The main objective of the
intervention study was to assess antidiabetic effects of daily bitter gourd
consumption of 2.5g powder over the course of eight weeks among prediabetic
individuals. MATERIALS AND METHODS: In a randomized placebo-controlled single
blinded clinical trial, 52 individuals with prediabetes were studied after
consuming a bitter gourd or a cucumber juice. For reducing the impact of between
subject differences in the study population, a crossover design was chosen with
eight weeks for each study period and four weeks washout in between. Fasting
plasma glucose was chosen as the primary outcome variable. RESULTS: Comparing the
different exposures, the CROS analysis (t=-2.23, p=0.031, r=0.326) revealed a
significant difference in the change of FPG of 0.31mmol/L (5.6mg/dL) with a trend
(R2=0,42387). The number of 44 finally complete data sets achieved a power of
0.82, with a medium-to-large effect size (Cohen's d 0.62). The effect was also
proven by a general linear mixed model (estimate 0.31; SE: 0.12; p: 0.01; 95%CI:
0.08; 0.54). Not all participants responded, but the higher the initial blood
glucose levels were, the more pronounced the effect was. No serious adverse
effects were observed. CONCLUSIONS: Bitter gourd supplementation appeared to have
benefits in lowering elevated fasting plasma glucose in prediabetes. The findings
should be replicated in other intervention studies to further investigate glucose
lowering effects and the opportunity to use bitter gourd for dietary self
management, especially in places where access to professional medical care is not
easily assured.
PMID- 29339111
TI - Stem Cells for Urinary Incontinence: Functional Differentiation or Cytokine
Effects?
AB - Minimally invasive stem cell therapy for stress urinary incontinence may provide
an effective nonsurgical treatment for this common condition. Clinical trials of
periurethral stem cell injection have been under way, and basic science research
has demonstrated the efficacy of both local and systemic stem cell therapies.
Results differ as to whether stem cells have a therapeutic effect by
differentiating into permanent, functional tissues or exert benefits through a
transient presence and the secretion of regenerative factors. This review
explores the fate of therapeutic stem cells for stress urinary incontinence and
how this may relate to their mechanism of action.
PMID- 29339112
TI - Reply to: "Reply to: 'Response to DAA therapy in the NHS England Early Access
Programme for rare HCV subtypes from low and middle income countries'".
PMID- 29339113
TI - Development of the liver: Insights into organ and tissue morphogenesis.
AB - Recent development of improved tools and methods to analyse tissues at the three
dimensional level has expanded our capacity to investigate morphogenesis of
foetal liver. Here, we review the key morphogenetic steps during liver
development, from the prehepatic endoderm stage to the postnatal period, and
consider several model organisms while focussing on the mammalian liver. We first
discuss how the liver buds out of the endoderm and gives rise to an asymmetric
liver. We next outline the mechanisms driving liver and lobe growth, and review
morphogenesis of the intra- and extrahepatic bile ducts; morphogenetic responses
of the biliary tract to liver injury are discussed. Finally, we describe the
mechanisms driving formation of the vasculature, namely venous and arterial
vessels, as well as sinusoids.
PMID- 29339114
TI - A systematic review and meta-analysis of cardiorespiratory fitness among
Indigenous populations in North America and circumpolar Inuit populations.
AB - Indigenous populations experience health disparities including increased obesity,
diabetes and cardiovascular disease rates. Cardiorespiratory fitness is
beneficial for maintaining positive health outcomes. The objective of this
systematic review is to evaluate cardiorespiratory fitness among Indigenous
populations including comparisons across genders, Indigenous identities, age
groups, decades, socio-demographic variables and in comparison to non-Indigenous
groups. Included articles reported various cardiorespiratory fitness measures
using maximal treadmill or cycle ergometer tests, 20 m shuttle run, 1 mile
run/walk test and 6 min walk test. From 14 databases searched in March 2017,
including MEDLINE, EMBASE and Scopus, 1069 citations were evaluated and 39
articles included, representing 32 investigations and 10,579 individuals. First
Nations/American Indian (FN/AI) adults have greater cardiorespiratory fitness
than Inuit. Inuit and FN/AI men and boys have higher cardiorespiratory fitness
than women and girls. Lower cardiorespiratory fitness is associated with obesity,
metabolic syndrome and a western lifestyle. Cardiorespiratory fitness has
declined among Inuit adults, averaging 51.7 +/- 7.9 mL.kg-1.min-1 in 1970 to 37.7
+/- 6.9 mL.kg-1.min-1 in 2000. Among men, FN/AI have greater cardiorespiratory
fitness compared to European-descents, and European-descents have greater
cardiorespiratory fitness compared to Inuit. The 1 mile run/walk time showed that
FN/AI boys, girls, and youth had faster times compared to European-descendants,
but 20 m shuttle run showed that European-descent boys and youth advanced to
further stages compared to FN/AI populations. Cardiorespiratory fitness is
declining, and among some Indigenous populations to lower levels than European
descent populations. Improving cardiorespiratory fitness for Indigenous
populations should be considered a primary health strategy.
PMID- 29339115
TI - Toddler drinks, formulas, and milks: Labeling practices and policy implications.
AB - Toddler drinks are a growing category of drinks marketed for young children 9-36
months old. Medical experts do not recommend them, and public health experts
raise concerns about misleading labeling practices. In the U.S., the toddler
drink category includes two types of products: transition formulas, marketed for
infants and toddlers 9-24 months; and toddler milks, for children 12-36 months
old. The objective of this study was to evaluate toddler drink labeling practices
in light of U.S. food labeling policy and international labeling recommendations.
In January 2017, we conducted legal research on U.S. food label laws and
regulations; collected and evaluated toddler drink packages, including nutrition
labels and claims; and compared toddler drink labels with the same brand's infant
formula labels. We found that the U.S. has a regulatory structure for food labels
and distinct policies for infant formula, but no laws specific to toddler drinks.
Toddler drink labels utilized various terms and images to identify products and
intended users; made multiple health and nutrition claims; and some stated there
was scientific or expert support for the product. Compared to the same
manufacturer's infant formula labels, most toddler drink labels utilized similar
colors, branding, logos, and graphics. Toddler drink labels may confuse consumers
about their nutrition and health benefits and the appropriateness of these
products for young children. To support healthy toddler diets and well-informed
decision-making by caregivers, the FDA can provide guidance or propose
regulations clarifying permissible toddler drink labels and manufacturers should
end inappropriate labeling practices.
PMID- 29339116
TI - Understanding Women's Subjective Sexual Arousal Within the Laboratory:
Definition, Measurement, and Manipulation.
AB - INTRODUCTION: Subjective sexual arousal (SSA) is positive, cognitive engagement
in sexual activity. SSA is considered an important aspect of the sexual
experience, as it has been found to facilitate sexual activity and, in situations
of chronically low or absent arousal, potentially cause distress. Despite the
clinical implications of SSA, a thorough review of how to manipulate SSA has yet
to be conducted. AIM: To review the state of knowledge about SSA in women,
including its definition, measurement, and the outcomes of studies attempting to
manipulate SSA within a laboratory setting. METHOD: A comprehensive search of the
electronic databases of PubMed and PsycINFO was conducted. The generated list of
articles was reviewed and duplicates were removed. Individual articles were
assessed for inclusion and, when appropriate, relevant content was extracted.
MAIN OUTCOME MEASURE: The potential effects of various manipulations of SSA in a
laboratory setting was the main outcome. RESULTS: 44 studies were included in
this review. Manipulations were grouped into 3 primary categories:
pharmacological (n = 16), cognitive (n = 22), and those based on changes to the
autonomic nervous system (n = 6). Results suggest that cognitive manipulation is
the most effective method of increasing SSA. Altering the relative balance of the
2 branches of the autonomic nervous system (the sympathetic nervous system and
the parasympathetic nervous system) also appears to be a promising avenue for
increasing SSA. CONCLUSION: This review supports the use of cognitive
manipulation for increasing women's SSA in a laboratory setting. Avenues for
future research and recommendations for clinicians are discussed. Handy AB,
Stanton AM, Meston CM. Understanding Women's Subjective Sexual Arousal Within the
Laboratory: Definition, Measurement, and Manipulation. Sex Med Rev 2018;6:201
216.
PMID- 29339117
TI - Expression, activation and processing of a novel plant milk-clotting aspartic
protease in Pichia pastoris.
AB - Galium verum, also known as Lady's Bedstraw or Cheese Rennet, is an herbaceous
perennial plant traditionally used in cheese-making. We used RACE PCR to isolate
novel enzymes from Galium verum with the ability to clot milk. This approach
generated two cDNA sequences (named preprogaline A and B) encoding proteins
displaying the typical plant aspartic protease primary structure. Preprogaline B
was expressed in the yeast Pichia pastoris, after deleting and replacing its
original signal peptide with the yeast alpha-factor signal peptide from
Saccharomyces cerevisiae. The secreted recombinant protein was obtained by
growing P. pastoris in YPD medium and had the ability to clot milk. The mature
form of progaline B is a heterodimeric glycosylated enzyme, with a molecular
weight of approximately 48 kDa, that contains a heavy (30.7 kDa) and a light
(13.5 kDa) polypeptide chains linked by disulfide bonds. Western blot analysis
revealed that progaline B is activated by the acidification of the yeast culture
medium and that enzymatic activation requires two steps. First the precursor
protein is cleaved into two polypeptide chains by partial removal of the plant
specific insert (PSI) present in plant aspartic proteases; this is later followed
by propeptide removal. By altering the pH of the P. pastoris culture medium, we
were able to obtain either active or inactive forms of the enzyme. Recombinant
progaline B displayed a kappa-casein hydrolysis pattern analogous to those
produced by the animal and microbial coagulants currently used in the dairy
industry, but it exhibited a different digestion profile on alpha- and beta
caseins. The plant protease progaline B displays milk-clotting activities
suitable for the production of novel dairy products.
PMID- 29339118
TI - Aerobic and anaerobic cellulose utilization by Paenibacillus sp. CAA11 and
enhancement of its cellulolytic ability by expressing a heterologous
endoglucanase.
AB - For cost-effective lignocellulosic biofuel/chemical production, consolidated
bioprocessing (CBP)-enabling microorganisms utilizing cellulose as well as
producing biofuel/chemical are required. A novel strain Paenibacillus sp. CAA11
isolated from sediment was found to be not only as a cellulose degrader under
both aerobic and strict anaerobic conditions but also as a producer of cellulosic
biofuel/chemicals. Paenibacillus sp. CAA11 secreted cellulolytic enzymes by its
own secretion system and produced ethanol as well as short-chain organic acids
(formic acid, acetic acid, lactic acid) from cellulose. Cellulolytic activity of
the strain was significantly enhanced by expressing a heterologous endoglucanase
168Cel5 from Bacillus subtilis under both aerobic and anaerobic conditions. The
strain harboring the 168cel5 gene revealed 2-fold bigger halo zone on Congo-red
plate and 1.75-fold more aerobic cellulose utilization in liquid medium compared
with the negative control. Notably, under anaerobic conditions, the recombinant
strain expressing 168Cel5 consumed 1.83-fold more cellulose (5.10 g/L) and
produced 5-fold more ethanol (0.65 g/L) along with 5-fold more total acids (1.6
g/L) compared with the control, resulting 2.73-fold higher yields. This result
demonstrates the potential of Paenibacillus sp. CAA11 as a suitable aerobic and
anaerobic CBP-enabling microbe with cellulolytic production of ethanol and short
chain organic acids.
PMID- 29339119
TI - Targeting of stress response pathways in the prevention and treatment of cancer.
AB - The hallmarks of tumor tissue are not only genetic aberrations but also the
presence of metabolic and oxidative stress as a result of hypoxia and lactic
acidosis. The stress activates several prosurvival pathways including metabolic
remodeling, autophagy, antioxidant response, mitohormesis, and glutaminolysis,
whose upregulation in tumors is associated with a poor survival of patients,
while their activation in healthy tissue with statins, metformin, physical
activity, and natural compounds prevents carcinogenesis. This review emphasizes
the dual role of stress response pathways in cancer and suggests the integrative
understanding as a basis for the development of rational therapy targeting the
stress response.
PMID- 29339120
TI - Symmetry of peripheral retinal nonperfusion in diabetic retinopathy by ischemic
index.
AB - PURPOSE: Diabetic retinopathy is the leading cause of blindness among working-age
adults in most developed countries. It affects eyes bilaterally and is generally
believed to be symmetrical, yet there are few studies evaluating the symmetry of
diabetic retinopathy. The purpose of the present study was to evaluate the
symmetry of the amount of peripheral retinal ischemia in patients with diabetic
retinopathy. METHODS: Ultra-widefield fluorescein angiography images were
obtained on both eyes of 54 subjects, mean age 56.4 years, from an urban eye
clinic. A single, high quality image from the arteriovenous phase of the
angiogram of each eye was selected for analysis. The total area of gradable
fundus and area of nonperfusion seen in the arteriovenous phase of the ultra
widefield fluorescein angiogram were determined. An ischemic index (ISI) was
calculated by dividing the non-perfused retinal area by the total retinal area
and multiplying by 100. RESULTS: The mean ISI OD was 11.27, mean ISI OS was
11.64. The mean absolute value (+/-SD) of ISI difference between OD and OS was
4.46+/-6.09. A difference in ISI of 10% or less was found in 92.6% of subjects. A
statistically significant correlation was found in the ISI between right and left
eyes (rs=0.80, p<0.0001) and there was no statistically significant difference in
ISI between the right and left eyes (p=0.85). CONCLUSION: Asymmetrical
retinopathy in diabetic patients is uncommon and additional pathological
processes should be considered in the presence of asymmetric DR.
PMID- 29339122
TI - Regnase-1, an Immunomodulator, Limits the IL-36/IL-36R Autostimulatory Loop in
Keratinocytes to Suppress Skin Inflammation.
PMID- 29339121
TI - HSF1, in association with MORC2, downregulates ArgBP2 via the PRC2 family in
gastric cancer cells.
AB - Arg Kinase-binding protein 2 (ArgBP2) is considered to be a scaffold protein that
coordinates multiple signaling pathways converging on cell adhesion and actin
cytoskeletal organization. It also plays an important role in blocking cancer
metastasis as a potential tumor suppressor. However, its regulation mechanisms in
tumor migration, especially in gastric cancer, are not fully understood. Here, we
identified an ArgBP2 enhancer and showed that heat shock factor 1 (HSF1) directly
interacted with microrchidia CW-type zinc finger 2 (MORC2) and bound to the
enhancer of ArgBP2. HSF1 was found to promote proliferation, migration and
invasion of gastric cancer cells. HSF1 or/and MORC2 increased recruitment of the
polycomb repressive complex 2 (PRC2), particularly enhancer of zeste homolog 2
(EZH2), to the ArgBP2 enhancer and catalyzed tri-methylation of lysine 27 on
histone H3 (H3K27me3), leading to transcriptional repression of ArgBP2. In
addition, HSF1 and MORC2-induced migration and invasion in gastric cancer cells
was dependent on ArgBP2 or EZH2. Clinical data exhibited a negative correlation
of ArgBP2 with MORC2, HSF1, and EZH2. Our results thus contribute to the
knowledge of the regulatory mechanism of HSF1 in down-regulating ArgBP2,
providing new insight into the HSF1&MORC2-PRC2-ArgBP2 signaling pathway and a
better understanding of their functions in gastric cancer cells.
PMID- 29339123
TI - Identical twins with XLA requiring differing amounts of 20% subcutaneous
immunoglobulin secondary to protein-losing enteropathy.
PMID- 29339124
TI - The first case of methemoglobinemia associated with omalizumab.
PMID- 29339125
TI - Prevalence and Outcomes of Primary Immunodeficiency in Hospitalized Children in
the United States.
AB - BACKGROUND: Primary immunodeficiency diseases (PIDDs) are rare yet life
threatening chronic conditions in children. The prevalence and outcomes of PIDDs
in the pediatric population in the United States are not well understood.
OBJECTIVE: The objectives of this study were to (1) determine the epidemiology of
children hospitalized with PIDD in the United States and (2) characterize the
clinical outcomes of hospitalized children with PIDDs. METHODS: Retrospective
cohort analysis of the 2003-2012 Kids' Inpatient Database of children aged 2-18
years admitted with a primary or secondary diagnosis code of PIDD was performed.
Secondary immunodeficiency diseases were excluded. RESULTS: There were 26,794
pediatric patients hospitalized with a diagnosis of a PIDD from 2003 to 2012. The
national prevalence of all PIDDs per 100,000 was 66.6, 82.2, 97.4, and 126.8 in
2003, 2006, 2009, and 2012, respectively. The highest prevalence was in children
0-5 years of age (15,105 hospitalizations; 56%). There was no difference in
prevalence between B-cell defects and T-cell defects. PIDDs affected all ethnic
populations equally. Respiratory-related diagnoses were the most common
comorbidity by an organ system. Overall mortality was 1.99%. Age was inversely
correlated with clinical outcome. Children 0-5 years had higher mortality (424
deaths, 79.85%), mean hospital charges ($35,480), and length of stay (LOS) (5.6
days) compared with older age cohorts. CONCLUSIONS: The prevalence of PIDDs in
the hospitalized pediatric population in the United States may have increased
over time. Younger age is associated with higher mortality, hospital costs, and
LOS. Further study is needed to determine cost-effective management strategies to
improve outcomes in infants and young children with PIDD.
PMID- 29339126
TI - Addressing the Impact and Unmet Needs of Nonadherence in Asthma and Chronic
Obstructive Pulmonary Disease: Where Do We Go From Here?
AB - Nonadherence to treatment, and its associated health and economic burden, is
particularly problematic in asthma and chronic obstructive pulmonary disease
management because of heterogeneous patient populations and the need for an
inhaled route of drug administration. Symptom variability, comorbidities, and
device switching further add to suboptimal adherence rates. As opposed to
controlled clinical trials, real-life studies show consistently low inhaler
adherence in daily practice, yet exact adherence rates have long been affected by
disagreement on standardized definitions. The recently developed Ascertaining
Barriers to Compliance taxonomy helps to address adherence research disparities
by identifying 3 phases of adherence (initiation, implementation [including
correct inhaler technique], and discontinuation). This review considers the
reasons for and impact of suboptimal adherence, together with summaries of key
studies that demonstrate how improving adherence can reduce exacerbations,
inhaled corticosteroid use (in cases of better inhaler technique),
hospitalizations, and treatment costs. Strategies to help ensure optimal
adherence are discussed, including the choice of a patient-tailored inhaler,
patient empowerment, education and training, and the potential of electronic
monitoring and digital technology. It is concluded that a combined effort from
payers, health care professionals, and manufacturers could make a real difference
to asthma and chronic obstructive pulmonary disease control, as well as to health
care budgets.
PMID- 29339127
TI - The Basophil Activation Test Can Be of Value for Diagnosing Immediate Allergic
Reactions to Omeprazole.
AB - BACKGROUND: Proton pump inhibitors (PPIs) are commonly used to treat
gastrointestinal diseases. Incidence of hypersensitivity reactions to PPIs has
risen, likely because of increased consumption. Their diagnosis is difficult,
with skin tests (STs) presenting low sensitivity, making it necessary to perform
drug provocation tests (DPTs). The value of in vitro tests for the diagnosis of
immediate reaction to PPI is unclear. OBJECTIVE: To analyze the diagnostic value
of the basophil activation test (BAT) in a group of patients diagnosed with
immediate allergy to omeprazole. METHODS: The study included 42 patients with
confirmed immediate allergic reactions to omeprazole confirmed by positive ST
results or DPT results and 22 age- and sex-matched subjects tolerant to PPIs. BAT
was performed with omeprazole, pantoprazole, and lansoprazole using CD63 and
CD203c as activation markers. RESULTS: ST sensitivity was 66.7% with a
specificity of 100%. BAT using CD63 with a stimulation index of more than 2 as
positive revealed a sensitivity of 73.8%, a specificity of 100%, a positive
predictive value of 100%, and a negative predictive value of 66.7%. BAT was
positive in 57.1% of patients with negative ST result, and thus by combining ST
and BAT we can correctly diagnose 85.7% of patients with immediate allergy to
omeprazole. CONCLUSION: BAT represents a complementary tool for inclusion in the
allergological workup for patients allergic to omeprazole. When combined with ST,
it can be of value to guide the clinician as to whether to perform a DPT.
PMID- 29339128
TI - Anxiety and Depression Effects During Drug Provocation Test.
AB - BACKGROUND: Drug provocation test (DPT) represents the gold standard for the
diagnosis of drug allergy. A DPT can be performed in a single-blind placebo
controlled manner. In anxiety and depressive disorders, patients need to be
evaluated to understand the nature of placebo reactions. OBJECTIVE: The aim of
this study was to evaluate the psychological profile of patients with reactions
to placebo during a DPT. METHODS: We consecutively enrolled patients with
suspected drug allergy undergoing a DPT preceded by the administration of the
placebo. All patients underwent the Hospital Anxiety and Depression Scale (HADS),
a questionnaire aimed to identify anxiety and depression, before the challenge
test. RESULTS: A total of 196 patients were enrolled into this study: 8 (4%)
patients resulted positive to the DPT, 60 (30.6%) demonstrated anxiety or
depression based on the HADS, and 54 had at least 1 placebo reaction during drug
provocation. There were statically significant correlations between the
positivity of the HADS and the finding of a placebo reaction (Fisher's exact
test: P < .001), and between the latter and a history of severe reactions to drug
(Fisher's exact test: P < .001). CONCLUSIONS: There is a significant and strong
correlation between the loss of psychic equilibrium and the development of a
placebo reaction during a DPT. We suggest the use the HADS or other validated
questionnaire in clinical practice before a DPT to evaluate the possible
psychiatric components.
PMID- 29339129
TI - Systemic Reactions in Pediatric Patients Receiving Standardized Allergen
Subcutaneous Immunotherapy with and without Seasonal Dose Adjustment.
AB - BACKGROUND: The 2003 Joint Task Force on Practice Parameters recommended
standardizing allergen subcutaneous immunotherapy (SCIT). Data from longitudinal
surveillance survey in North America reported a systemic reaction (SR) rate of
0.1% to 0.2% of injection visits. The rate of SR to standardized SCIT in
pediatric patients has not been well evaluated. OBJECTIVE: The objective of this
study was to evaluate the rate of SRs to standardized SCIT in pediatric patients
aged 5 to 18 years in a single tertiary care center in the United States.
METHODS: A retrospective chart review was conducted in 2 groups: group 1 started
SCIT within a period extending from January 2009 to June 2012, whereas group 2
started SCIT within a period extending from January 2013 to June 2016. The
protocol was modified in group 2 such that updosing and maintenance doses were
adjusted in the spring for tree and grass pollen and in the fall for weed pollen.
RESULTS: There were a total of 128 patients in group 1 and 118 patients in group
2. The rate of SR was 0.429% in group 1 and 0.364% in group 2, which was not
significant. There was no difference in the severity of SR in the 2 groups with
no-fatal or near-fatal SR noted. Asthma was a significant risk factor in the
younger age subgroup aged 5 to 11 years. CONCLUSIONS: Standardized SCIT appears
to be associated with an SR rate of 0.429% to 0.364% of visits in pediatric
patients. Protocol modification did not lead to a significant drop in SR. Larger
multicenter studies are required to further evaluate the rate of SRs from
standardized SCIT.
PMID- 29339130
TI - Fixed Drug Eruption Related to Cefixime in an Adolescent Case.
PMID- 29339132
TI - Exogenous progesterone hypersensitivity associated with recurrent pregnancy loss.
PMID- 29339131
TI - Childhood Asthma: Is It All About Bacteria and Not About Viruses? A Pro/Con
Debate.
PMID- 29339133
TI - Antithrombin III-Binding Site Analysis of Low-Molecular-Weight Heparin Fractions.
AB - Low-molecular-weight heparins (LMWHs) are widely used as clinical anticoagulant
drugs. LMWHs are heterogeneous and highly negatively charged glycans prepared by
chemical or enzymatic depolymerization of unfractionated heparin. The detailed
structural analysis of a LMWH is essential for the drug quality control. In this
study, an LMWH, enoxaparin sodium (a generic version of Lovenox) was separated
into different molecular weight fractions by a Superdex peptide column. The
disaccharide compositions, 3-O-sulfo group-containing tetrasaccharides
composition, and antithrombin III-binding affinity of the fractions from this
LMWH were analyzed. The results showed that all the fractions had very similar
disaccharide and 3-O-sulfo group-containing tetrasaccharide compositions, but the
fraction containing larger-sized chains had higher antithrombin III-binding
affinity.
PMID- 29339134
TI - A Small-Scale Process for Predicting Donnan and Volume Exclusion Effects During
Ultrafiltration/Diafiltration Process Development.
AB - Achieving the desired final protein formulation using
ultrafiltration/diafiltration (UF/DF) operations is an essential component of
many protein purification processes. It is well documented that differences in
the excipient and buffer concentrations exist between the DF and retentate
solutions when they have achieved equilibrium. Several publications have proposed
ways to calculate these differences. However, the accuracy of these methods has
been limited by the use of an estimated protein charge value. In this article, a
small-scale system is described, which can accurately determine the protein
charge by making buffer and excipient concentration measurements and applying the
determined values to the Donnan and volume exclusion equations. This information
can be utilized to generate a standard curve, which in turn can be applied to at
scale UF/DF operations. For 2 different antibodies, the standard curve generated
by the small-scale system yielded buffer concentrations and pH values that agreed
well with those generated after UF/DF operations, whereas using the theoretical
protein charge caused a departure from the measured results. This model also
provides good estimates as to how the final formulation pH and buffer
concentration vary as a function of the pH and buffer concentration in the DF
buffer. This information is of important utility for the accurate formulation of
high-concentration protein solutions (>100 mg/mL) where the coconcentration of
buffers and the volume exclusion of certain excipients are amplified. The low
material requirements of the small-scale system are a major benefit for early
phase formulation and process development when sufficient time and material may
not be available, in particular to ensure successful UF/DF operations for the
development of high protein concentration formulations.
PMID- 29339135
TI - Quantitative Monitoring the Anti-Solvent Crystallization and Storage Process for
Nandrolone by Near-Infrared Spectroscopy.
AB - A novel hydrate (SH2O) of nandrolone was prepared by anti-solvent methods. The
crystallization processes with 2 schemes (A and B) were monitored by in-line near
infrared (NIR) spectroscopy. The amounts of SH2O in powder samples obtained by
the anti-solvent crystallization and storage process were quantified by NIR
combined with chemometrics methods. In-line NIR spectra from 4500 to 8000 cm-1
were chosen to capture physicochemical changes during the whole crystallization
process. The combination of the principal component results with offline
characterization (scanning electron microscopy, powder X-ray diffraction, NIR)
data showed that both schemes yielded high purity SH2O products, but the
crystallization speed of scheme B was significantly accelerated. It was
demonstrated that in-line NIR spectroscopy combined with principal component
analysis can be very useful to monitor in real time and control the anti-solvent
crystallization process. Moreover, the solubility and the solid-state
transformation of nandrolone under different storage conditions were
investigated. The apparent solubility of SH2O was 2.19-2.44 times of Form I, and
SH2O was relatively stable when stored at a high relative humidity and
temperature below 25 degrees C.
PMID- 29339136
TI - Development of Orally Applicable, Combinatorial Drug-Loaded Nanoparticles for the
Treatment of Fibrosarcoma.
AB - Nanoparticulate systems have been receiving a significant attention especially
for the treatment of cancer but one of the main hurdles is to produce these
developed and high-tech nanosystems in large quantities. Anticancer drug
formulations are generally designed for parenteral administrations but oral
administration is still the most convenient route. In this study, orally
applicable nano-sized chitosan nanoparticles (NPs) were successfully prepared
using Nano Spray Dryer. It is possible to produce these NPs in large quantities
by simply increasing the processing time using the machine without changing any
parameter. A chemotherapeutic agent (imatinib mesylate; IMA) and nonsteroidal
anti-inflammatory drug (dexketoprofen trometamol) were loaded together in these
NPs. NPs were also functionalized with polyethylene glycol and folic acid to
obtain long circulating NPs and tumor targeting. The antitumoral activities of
formulations showed that these developed NPs can enhance the effectiveness.
Animal experiments were performed on fibrosarcoma-bearing mice model, and the
treatment with 0.8 mg/MUL/kg IMA-loaded chitosan NPs was found to be successful
to slow down the growth of tumors. The tumor tissues were removed from the
animals and enzymatic activities were evaluated. The inhibitory effect of
tyrosine kinase was found to be enhanced from 36.4% to 68.4% when IMA was used in
combination with dexketoprofen trometamol. Furthermore, all dried NPs were found
to be stable for more than a year at 25 degrees C. Presented results show that
these developed combinatorial drug-loaded NPs can be used for the treatment of
fibrosarcoma, and these data can provide an insight, new strategies for
productions or alternatives in cancer treatment.
PMID- 29339137
TI - Oxygen-induced alterations in the expression of chromatin modifying enzymes and
the transcriptional regulation of imprinted genes.
AB - Embryo culture and assisted reproductive technologies have been associated with a
disproportionately high number of epigenetic abnormalities in the resulting
offspring. However, the mechanisms by which these techniques influence the
epigenome remain poorly defined. In this study, we evaluated the capacity of
oxygen concentration to influence the transcriptional control of a selection of
key enzymes regulating chromatin structure. In mouse embryonic stem cells, oxygen
concentrations modulated the transcriptional regulation of the TET family of
enzymes, as well as the de novo methyltransferase Dnmt3a. These transcriptional
changes were associated with alterations in the control of multiple imprinted
genes, including H19, Igf2, Igf2r, and Peg3. Similarly, exposure of in vitro
produced bovine embryos to atmospheric oxygen concentrations was associated with
disruptions in the transcriptional regulation of TET1, TET3, and DNMT3a, along
with the DNA methyltransferase co-factor HELLS. In addition, exposure to high
oxygen was associated with alterations in the abundance of transcripts encoding
members of the Polycomb repressor complex (EED and EZH2), the histone
methyltransferase SETDB1 and multiple histone demethylases (KDM1A, KDM4B, and
KDM4C). These disruptions were accompanied by a reduction in embryo viability and
suppression of the pluripotency genes NANOG and SOX2. These experiments
demonstrate that oxygen has the capacity to modulate the transcriptional control
of chromatin modifying genes involved in the establishment and maintenance of
both pluripotency and genomic imprinting.
PMID- 29339139
TI - Improved coronary magnetic resonance angiography using gadobenate dimeglumine in
pediatric congenital heart disease.
AB - BACKGROUND: CMRA in pediatrics remains challenging due to the smaller vessel
size, high heart rates (HR), potential image degradation caused by limited
patient cooperation and long acquisition times. High-relaxivity contrast agents
have been shown to improve coronary imaging in adults, but limited data is
available in children. We sought to investigate whether gadobenate dimeglumine
(Gd-BOPTA) together with self-navigated inversion-prepared coronary magnetic
resonance angiography (CMRA) sequence design improves coronary image quality in
pediatric patients. METHODS: Forty consecutive patients (mean age 6+/-2.8years;
73% males) were prospectively recruited for a 1.5-T MRI study under general
anesthesia. Two electrocardiographic-triggered free breathing steady-state free
precession (SSFP) angiography sequences (A and B) with isotropic spatial
resolution (1.3mm3) were acquired using a recently developed image-based self
navigation technique. Sequence A was acquired prior to contrast administration
using T2 magnetization preparation (T2prep). Sequence B was acquired 5-8min after
a bolus of Gd-BOPTA with the T2prep replaced by an inversion recovery (IR) pulse
to null the signal from the myocardium. Scan time, signal-to noise and contrast
to-noise ratios (SNR and CNR), vessel wall sharpness (VWS) and qualitative visual
score for each sequence were compared. RESULTS: Scan time was similar for both
sequences (5.3+/-1.8 vs 5.2+/-1.5min, p=.532) and average heart rate (78+/-14.7
vs 78+/-14.5bpm, p=.443) remained constant throughout both acquisitions. Sequence
B resulted in higher SNR (12.6+/-4.4 vs 31.1+/-7.4, p<.001) and CNR (9.0+/-1.8 vs
13.5+/-3.7, p<.001) and provided improved coronary visualization in all coronary
territories (VWS A=0.53+/-0.07 vs B=0.56+/-0.07, p=.001; and visual scoring
A=3.8+/-0.59 vs B=4.1+/-0.53, p<.001). The number of non-diagnostic coronary
segments was lower for sequence B [A=42 (13.1%) segments vs B=33 (10.3%)
segments; p=.002], and contrary to the pre-contrast sequence, never involved a
proximal segment. These results were independent of the patients' age, body
surface area and HR. CONCLUSIONS: The use of Gd-BOPTA with a 3D IR SSFP CMRA
sequence results in improved coronary visualization in small infants and young
children with high HR within a clinically acceptable scan time.
PMID- 29339138
TI - Hyperglycaemia disrupts conducted vasodilation in the resistance vasculature of
db/db mice.
AB - Vascular dysfunction in small resistance arteries is observed during chronic
elevations in blood glucose. Hyperglycaemia-associated effects on endothelium
dependent vasodilation have been well characterized, but effects on conducted
vasodilation in the resistance vasculature are not known. Small mesenteric
arteries were isolated from healthy and diabetic db/db mice, which were used as a
model of chronic hyperglycaemia. Endothelium-dependent vasodilation via the Gq/11
coupled proteinase activated receptor 2 (PAR2) was stimulated with the selective
agonist SLIGRL. The Ca2+-sensitive fluorescent indicator fluo-8 reported changes
in endothelial cell (EC) [Ca2+]i, and triple cannulated bifurcating mesenteric
arteries were used to study conducted vasodilation. Chronic hyperglycaemia did
not affect either EC Ca2+ or local vasodilation to SLIGRL. However, both acute
and chronic exposure to high glucose or the mannitol osmotic control attenuated
conducted vasodilation to 10MUM SLIGRL. This investigation demonstrates for the
first time that a hypertonic solution containing glucose or mannitol can
interfere with the spread of a hyperpolarizing current along the endothelium in a
physiological setting. Our findings reiterate the importance of studying the
effects of hyperglycaemia in the vasculature, and provide the basis for further
studies regarding the modulation of junctional proteins involved in cell to cell
communication by diseases such as diabetes.
PMID- 29339140
TI - [Could we perform vaginal mesh surgery for treatment of pelvic organ prolapse in
elderly women?]
AB - INTRODUCTION: Prevalence of pelvic organ prolapse will increase with the aging of
the population. Concerning the treatment of pelvic organ prolapse, transvaginal
route is often preferred for elderly women. However few data are available
concerning transvaginal mesh surgery in this population. The aim of this study
was to compare efficiency and complications of transvaginal mesh surgery between
women aged over 75 and younger women. MATERIALS AND METHODS: A monocentric,
retrospective study included all women who underwent anterior sacrospinous
suspension with mesh for treatment of pelvic organ prolapse. The primary endpoint
was anatomical success at the last follow-up, defined by a pelvic organ prolapse
stage 0 or 1 of POP-Q classification. The secondary endpoints were rate of
complications and urinary, colorectal and sexual functional results. RESULTS: We
included 329 patients, 69 were under 75 years old and 260 were aged over 75. The
median of follow-up was 12 months (IQR: 6). The rate of anatomical success was
significantly higher in patients aged over 75: 92% versus 85% in younger patients
(P=0.02). However this difference was no more significant in multivariate
analysis after inclusion of confusions factors (P=0.82). The rate of
perioperative complications was low and similar in the 2 groups even in
multivariate analysis. CONCLUSION: Utero-vaginal suspension using bilateral
vaginal anterior sacrospinous fixation with mesh seems to achieve at least
similar results between women aged more than 75 years and younger women. There is
no excess risk of complications in elderly women. LEVEL OF EVIDENCE: 4.
PMID- 29339141
TI - [Immunotherapy in renal cell carcinoma: A booming clinical research].
AB - CONTEXT: Nivolumab, an anti-PD1 immune control point inhibitor, is the first
treatment that has improved the overall survival of patients after first-line
metastatic renal cell carcinoma in 2015. Over the past two years, a large number
of trials on these treatments and the interest of associations are being
evaluated. OBJECTIVE: In this article, we propose to summarize the clinical
development of checkpoint inhibitors to assess the direction of clinical research
in this area. DOCUMENTARY SOURCE: A systematic review of the literature was
performed in PubMed/Medline database and Meeting Library Asco by searching for
articles in French or English published on immunotherapy in renal cell carcinoma.
The research was limited to abstracts and articles published from 2014 to 2017.
SELECTION OF TRIALS: We identified 349 publications and abstracts and selected 17
references from prospective studies. RESULTS: Recent data on checkpoint
inhibitors, as well as their combination with tyrosine kinase inhibitors or with
anti-angiogenic agents or with indoleamine 2, 3-dioxygenase 1 in renal cell
carcinoma and the latest advances in vaccine therapy have been reported.
CONCLUSION: In 2017, immunotherapy combined with other treatments is likely to
lead to a paradigm shift in the clinical management of patients. The combination
of nivolumab and ipilimumab in the first line will revolutionize the therapeutic
management of patients with metastatic renal cell carcinoma.
PMID- 29339142
TI - [Comment on "Open prostatectomy versus 180-W XPS GreenLight laser vaporization:
Long-term functional outcome for prostatic adenomas >80g" (Lanchon, in press )].
PMID- 29339143
TI - Gene silencing reveals multiple functions of Na+/K+-ATPase in the salmon louse
(Lepeophtheirus salmonis).
AB - Na+/K+-ATPase has a key function in a variety of physiological processes
including membrane excitability, osmoregulation, regulation of cell volume, and
transport of nutrients. While knowledge about Na+/K+-ATPase function in
osmoregulation in crustaceans is extensive, the role of this enzyme in other
physiological and developmental processes is scarce. Here, we report
characterization, transcriptional distribution and likely functions of the newly
identified L. salmonis Na+/K+-ATPase (LsalNa+/K+-ATPase) alpha subunit in various
developmental stages. The complete mRNA sequence was identified, with 3003 bp
open reading frame encoding a putative protein of 1001 amino acids. Putative
protein sequence of LsalNa+/K+-ATPase revealed all typical features of Na+/K+
ATPase and demonstrated high sequence identity to other invertebrate and
vertebrate species. Quantitative RT-PCR analysis revealed higher LsalNa+/K+
ATPase transcript level in free-living stages in comparison to parasitic stages.
In situ hybridization analysis of copepodids and adult lice revealed LsalNa+/K+
ATPase transcript localization in a wide variety of tissues such as nervous
system, intestine, reproductive system, and subcuticular and glandular tissue.
RNAi mediated knock-down of LsalNa+/K+-ATPase caused locomotion impairment, and
affected reproduction and feeding. Morphological analysis of dsRNA treated
animals revealed muscle degeneration in larval stages, severe changes in the
oocyte formation and maturation in females and abnormalities in tegmental glands.
Thus, the study represents an important foundation for further functional
investigation and identification of physiological pathways in which Na+/K+-ATPase
is directly or indirectly involved.
PMID- 29339144
TI - Addressing barriers to effective cancer immunotherapy with nanotechnology:
achievements, challenges, and roadmap to the next generation of
nanoimmunotherapeutics.
AB - Cancer is a complex systemic disorder that affects many organs and tissues and
arises from the altered function of multiple cellular and molecular mechanisms.
One of the systems malfunctioning in cancer is the immune system. Restoring and
improving the ability of the immune system to effectively recognize and eradicate
cancer is the main focus of immunotherapy, a topic which has garnered recent and
significant interest. The initial excitement about immunotherapy, however, has
been challenged by its limited efficacy in certain patient populations and the
development of adverse effects such as therapeutic resistance and autoimmunity.
At the same time, a number of advances in the field of nanotechnology have sought
to address the challenges faced by modern immunotherapeutics and allow these
therapeutic strategies to realize their full potential. This endeavour requires
an understanding of not only the immunological barriers in cancer but also the
mechanisms by which modern technologies and immunotherapeutics modulate the
function of the immune system. Herein, we summarize the major barriers relevant
to cancer immunotherapy and review current progress in addressing these obstacles
using various approaches and clinically approved therapies. We then discuss the
remaining challenges and how they can be addressed by nanotechnology. We lay out
translational considerations relevant to the therapies described and propose a
framework for the development of next-generation nanotechnology-enabled
immunotherapies.
PMID- 29339146
TI - Microspheres as intraocular therapeutic tools in chronic diseases of the optic
nerve and retina.
AB - Pathologies affecting the optic nerve and the retina are one of the major causes
of blindness. These diseases include age-related macular degeneration (AMD),
diabetic retinopathy (DR) and glaucoma, among others. Also, there are genetic
disorders that affect the retina causing visual impairment. The prevalence of
neurodegenerative diseases of the posterior segment is increased as most of them
are related with the elderly. Even with the access to different treatments, there
are some challenges in managing patients suffering retinal diseases. One of them
is the need for frequent interventions. Also, an unpredictable response to
therapy has suggested that different pathways may be playing a role in the
development of these diseases. The management of these pathologies requires the
development of controlled drug delivery systems able to slow the progression of
the disease without the need of frequent invasive interventions, typically
related with endophthalmitis, retinal detachment, ocular hypertension, cataract,
inflammation, and floaters, among other. Biodegradable microspheres are able to
encapsulate low molecular weight substances and large molecules such as
biotechnological products. Over the last years, a large variety of active
substances has been encapsulated in microspheres with the intention of providing
neuroprotection of the optic nerve and the retina. The purpose of the present
review is to describe the use of microspheres in chronic neurodegenerative
diseases affecting the retina and the optic nerve. The advantage of
microencapsulation of low molecular weight drugs as well as therapeutic peptides
and proteins to be used as neuroprotective strategy is discussed. Also, a new use
of the microspheres in the development of animal models of neurodegeneration of
the posterior segment is described.
PMID- 29339147
TI - Neural signatures for active maintenance and interference during working memory
updating.
AB - Although working memory (WM) is amongst the most studied neurocognitive
functions, temporal patterns of its component processes are not fully understood.
We examined the neural underpinnings of active maintenance and interference
management in the n-back task by manipulating load (1-back vs 3-back) and
including so-called lure stimuli. ERPs of 27 young adults revealed that the 1
back condition enabling active maintenance showed a positive slow wave (PSW)
prior to the next stimulus (-600-0 ms) and augmented P2 (190-290 ms) and P3b (330
430 ms) responses after the stimulus appeared, albeit the latter effects were
driven by the initial PSW. Moreover, PSW amplitude correlated negatively with
reaction time in the 1-back condition. Responses to lures showed interference,
accompanied with different ERP effects for the two load levels. Our results
support the view that PSW reflects efficient WM maintenance and suggest two
distinct neuronal correlates for interference in WM.
PMID- 29339148
TI - Biochemical characterization of Campylobacter jejuni PNPase, an exoribonuclease
important for bacterial pathogenicity.
AB - Bacteria need to promptly respond to environmental changes. Ribonucleases
(RNases) are key factors in the adaptation to new environments by enabling a
rapid adjustment in RNA levels. The exoribonuclease polynucleotide phosphorylase
(PNPase) is essential for low-temperature cell survival, affects the synthesis of
proteins involved in virulence and has an important role in swimming, cell
adhesion/invasion ability, and chick colonization in C. jejuni. However, the
mechanism of action of this ribonuclease is not yet known. In this work we have
characterized the biochemical activity of C. jejuni PNPase. Our results
demonstrate that Cj-PNP is a processive 3' to 5' exoribonuclease that degrades
single-stranded RNAs. Its activity is regulated according to the temperature and
divalent ions. We have also shown that the KH and S1 domains are important for
trimerization, RNA binding, and, consequently, for the activity of Cj-PNP. These
findings will be helpful to develop new strategies for fighting against C. jejuni
and may be extrapolated to other foodborne pathogens.
PMID- 29339149
TI - SkinEthicTM RHE for in vitro evaluation of skin irritation of medical device
extracts.
AB - According to ISO 10993 standards for biocompatibility of medical devices, skin
irritation is one of the three toxicological endpoints to be always addressed in
a biological risk assessment. This work presents a new protocol to assess this
endpoint in vitro rather than in vivo. The protocol was adapted to medical
devices extracts from the OECD TG 439 with the SkinEthicTM RHE model as test
system. It was challenged with irritant chemicals, Sodium Dodecyl Sulfate, Lactic
Acid and Heptanoic Acid spiked in polar solvents, sodium chloride solution or
phosphate buffer saline and non-polar solvent, Sesame Oil. Cell viability
measured by MTT reduction after 24 h exposure was used as readout. Quantification
of IL-1alpha release as secondary readout did not increased performance. Samples
of heat-pressed polyvinyl chloride (PVC) and silicone sheets infused with or
without known irritant (4% Genapol-X80, 6% Genapol-X100 and 15% SDS) were tested
after extraction in polar and non-polar solvents. Medical device extracts are
classified irritant when the cell viability is inferior or equal to 50%, compared
to the negative controls tissues, in at least one extraction solvent. The correct
classification of all the samples confirmed the good performance of this new
protocol for in vitro skin irritation of medical devices extracts with the
SkinEthicTM RHE model. Seven naive laboratories were trained in prevision of the
Round Robin Study to evaluate Reconstructed Human Epidermis (RhE) models as in
vitro skin irritation test for detection of irritant potential in medical device
extracts.
PMID- 29339145
TI - Ocular delivery of proteins and peptides: Challenges and novel formulation
approaches.
AB - The impact of proteins and peptides on the treatment of various conditions
including ocular diseases over the past few decades has been advanced by
substantial breakthroughs in structural biochemistry, genetic engineering,
formulation and delivery approaches. Formulation and delivery of proteins and
peptides, such as monoclonal antibodies, aptamers, recombinant proteins and
peptides to ocular tissues poses significant challenges owing to their large
size, poor permeation and susceptibility to degradation. A wide range of advanced
drug delivery systems including polymeric controlled release systems, cell-based
delivery and nanowafers are being exploited to overcome the challenges of
frequent administration to ocular tissues. The next generation systems integrated
with new delivery technologies are anticipated to generate improved efficacy and
safety through the expansion of the therapeutic target space. This review will
highlight recent advances in formulation and delivery strategies of protein and
peptide based biopharmaceuticals. We will also describe the current state of
proteins and peptides based ocular therapy and future therapeutic opportunities.
PMID- 29339150
TI - Altered function of neuronal L-type calcium channels in ageing and
neuroinflammation: Implications in age-related synaptic dysfunction and cognitive
decline.
AB - The rapid developments in science have led to an increase in human life
expectancy and thus, ageing and age-related disorders/diseases have become one of
the greatest concerns in the 21st century. Cognitive abilities tend to decline as
we get older. This age-related cognitive decline is mainly attributed to aberrant
changes in synaptic plasticity and neuronal connections. Recent studies show that
alterations in Ca2+ homeostasis underlie the increased vulnerability of neurons
to age-related processes like cognitive decline and synaptic dysfunctions.
Dysregulation of Ca2+ can lead to dramatic changes in neuronal functions. We
discuss in this review, the recent advances on the potential role of dysregulated
Ca2+ homeostasis through altered function of L-type voltage gated Ca2+ channels
(LTCC) in ageing, with an emphasis on cognitive decline. This review therefore
focuses on age-related changes mainly in the hippocampus, and with mention of
other brain areas, that are important for learning and memory. This review also
highlights age-related memory deficits via synaptic alterations and
neuroinflammation. An understanding of these mechanisms will help us formulate
strategies to reverse or ameliorate age-related disorders like cognitive decline.
PMID- 29339151
TI - Practical considerations for obtaining high quality quantitative computed
tomography data of the skeletal system.
AB - Quantitative CT (QCT) analysis involves the calculation of specific parameters
such as bone volume and density from CT image data, and can be a powerful tool
for understanding bone quality and quantity. However, without careful attention
to detail during all steps of the acquisition and analysis process, data can be
of poor- to unusable-quality. Good quality QCT for research requires meticulous
attention to detail and standardization of all aspects of data collection and
analysis to a degree that is uncommon in a clinical setting. Here, we review the
literature to summarize practical and technical considerations for obtaining high
quality QCT data, and provide examples of how each recommendation affects
calculated variables. We also provide an overview of the QCT analysis technique
to illustrate additional opportunities to improve data reproducibility and
reliability. Key recommendations include: standardizing the scanner and data
acquisition settings, minimizing image artifacts, selecting an appropriate
reconstruction algorithm, and maximizing repeatability and objectivity during QCT
analysis. The goal of the recommendations is to reduce potential sources of error
throughout the analysis, from scan acquisition to the interpretation of results.
PMID- 29339152
TI - Biogenic triamine and tetraamine activate core catalytic ability of Tetrahymena
group I ribozyme in the absence of its large activator module.
AB - Group I intron ribozymes share common core elements that form a three-dimensional
structure responsible for their catalytic activity. This core structure is
unstable without assistance from additional factors that stabilize its tertiary
structure. We examined biogenic triamine and tetraamine and also their fragments
for their abilities to stabilize a structurally unstable group I ribozyme,
DeltaP5 ribozyme, derived from the Tetrahymena group I intron ribozyme by
deleting its large activator module. Biogenic triamine (spermidine) and
tetraamine (spermine) efficiently activated the DeltaP5 ribozyme under conditions
where the ribozyme was virtually inactive. These observations suggested that
polyamines are promising small molecule modulators to activate and possibly
inhibit the core catalytic ability of group I ribozymes.
PMID- 29339153
TI - TEMPORARY REMOVAL: Inhibition of COX-2 and 5-LOX regulates the progression of
colorectal cancer by promoting PTEN and suppressing PI3K/AKT pathway.
AB - The publisher regrets that this article has been temporarily removed. A
replacement will appear as soon as possible in which the reason for the removal
of the article will be specified, or the article will be reinstated. The full
Elsevier Policy on Article Withdrawal can be found
athttps://www.elsevier.com/about/our-business/policies/article-withdrawal.
PMID- 29339154
TI - A new hepatitis B virus e antigen-negative strain gene used as a reference
sequence in an animal model.
AB - Infection with hepatitis B virus (HBV) e-antigen (HBeAg)-negative strains is
increasingly prevalent. Currently, detailed information of the obtained natural
HBV strain is not available except for the B genotype and HBeAg-negative. The aim
of the present study was to characterize the natural genetic variation of the
HBeAg-negative strain and investigate its function. The genic sequence was
determined using Sanger sequencing, and compared to related sequences using
alignment and phylogenetic analysis. In vivo, virus-specific serum markers were
investigated in CBA/CaJ mice. The sequence had a full genome length of 3215
nucleotides. Sites 122, 125, 127, and 160 in S regions were identified as lysine,
threonine, proline, and lysine respectively. The main four point variants
including A1762T, G1764A, G1896A, and G1899A were detected in the full-length
genome. The genotype of the sequence was B, with sub-genotype B2 and serological
subtype adw2. The characterize of the natural genetic variation strain showed no
reported drug-resistant variant in P region and no reported immune escape site in
S region. The strain will increase viral replication and infection for mutations
A1762T and G1764A in the basal core promoter region, and mutations G1896A and
G1899A in the pre-core region. The G1896A variant resulted in a premature stop
codon and abolished HBeAg expression. HBsAg persisted for 26 weeks and HBeAg was
still negative in CBA/CaJ mice. The present sequence is representative of the
HBeAg-negative genome and may serve as a valuable reference for studying HBeAg
negative strains. The present findings were successfully verified in CBA/CaJ
mice, demonstrating good applicability of the sequence.
PMID- 29339155
TI - Truncated CD200 stimulates tumor immunity leading to fewer lung metastases in a
novel Wistar rat metastasis model.
AB - CD200 mediates immunosuppression in immune cells that express its receptor,
CD200R. There are two CD200 variants; truncated CD200 that lacks the part of N
terminal sequence necessary for CD200R binding (CD200S) and full-length CD200
(CD200L). We established a novel lung metastasis model by subcutaneously
transplanting C6 glioma cells into the backs of neonatal Wistar rats. All
transplanted rats developed large back tumors, nearly 90% of which bore lung
metastases. To compare the effects of CD200S and CD200L on tumor immunity, CD200L
(C6-L)- or CD200S (C6-S)-expressing C6 cells were similarly transplanted. The
results showed that 100% of rats with C6-L tumors developed lung metastases,
while metastases were found in only 44% of rats with C6-S tumors (n = 25). Tumors
disappeared in approximately 20% of the C6-S-bearing rats, and these animals
evaded death 180 d after transplantation, while all C6-L tumor-bearing rats died
after 45 d. Next generation sequencing revealed that C6-S tumors expressed
chemokines and granzyme B at much higher levels than C6-L tumors. Flow cytometry
revealed that C6-S tumors contained more dead cells and more CD45+ cells,
including natural killer cells and CD8+ lymphocytes. In particular, multiple
subsets of dendritic cells expressing CD11c, MHC class II, CD8, and/or CD103 were
more abundant in C6-S than in C6-L tumors. These results suggested that CD200S
induced the accumulation of multiple dendritic cell subsets that activated
cytotoxic T lymphocytes, leading to the elimination of metastasizing tumor cells.
PMID- 29339156
TI - Structure and function of cytoplasmic serine hydroxymethyltransferase from Pichia
pastoris.
AB - Serine hydroxymethyltransferase (SHMT) catalyzes the interconversion of serine
and glycine, which is crucial for one carbon metabolism. Here, we report the
first crystal structure of cytoplasmic SHMT from Pichia pastoris (pcSHMT)
diffracted to 2.5 A resolution in space group C2221. PcSHMT was a contaminant
with our target protein expressed in Pichia pastoris and confirmed by mass
spectrometry. The overall structure of pcSHMT is similar to Human mitochondrial
SHMT and different to E. coli SHMT. Interestingly, the oligomerization of pcSHMT
expressed in eukaryotic or prokaryotic system differs significantly and is
regulated by pyridoxal-5'-phosphate. Our results revealed a close evolutionary
relationship between Pichia pastoris and Human mitochondria.
PMID- 29339157
TI - Drastic stability change of X-X mismatch in d(CXG) trinucleotide repeat disorders
under molecular crowding condition.
AB - The trinucleotide repeat d(CXG) (X = A, C, G or T) is the most common sequence
causing repeat expansion disorders. The formation of non-canonical structures,
such as hairpin structures with X-X mismatches, has been proposed to affect gene
expression and regulation, which are important in pathological studies of these
devastating neurological diseases. However, little information is available
regarding the thermodynamics of the repeat sequence under crowded cellular
conditions where many non-canonical structures such as G-quadruplexes are highly
stabilized, while duplexes are destabilised. In this study, we investigated the
different stabilities of X-X mismatches in the context of internal d(CXG) self
complementary sequences in an environment with a high concentration of cosolutes
to mimic the crowding conditions in cells. The stabilities of full-matched
duplexes and duplexes with A-A, G-G, and T-T mismatched base pairs under
molecular crowding conditions were notably decreased compared to under dilute
conditions. However, the stability of the DNA duplex with a C-C mismatch base
pair was only slightly destabilised. Investigating different stabilities of X-X
mismatches in d(CXG) sequences is important for improving our understanding of
the formation and transition of multiple non-canonical structures in
trinucleotide repeat diseases, and may provide insights for pathological studies
and drug development.
PMID- 29339158
TI - Myosin XI localizes at the mitotic spindle and along the cell plate during plant
cell division in Physcomitrella patens.
AB - Cell division is a fundamental biological process that has been extensively
investigated in different systems. Similar to most eukaryotic cells, plant cells
assemble a mitotic spindle to separate replicated chromosomes. In contrast, to
complete cell division, plant cells assemble a phragmoplast, which is composed of
aligned microtubules and actin filaments. This structure helps transport vesicles
containing new cell wall material, which then fuse to form the cell plate; the
cell plate will expand to create the new dividing cell wall. Because vesicles are
known to be transported by myosin motors during interphase, we hypothesized this
could also be the case during cell division and we investigated the localization
of the plant homologue of myosin V - myosin XI, in cell division. In this work,
we used the protonemal cells of the moss Physcomitrella patens as a model,
because of its simple cellular morphology and ease to generate transgenic cell
lines expressing fluorescent tagged proteins. Using a fluorescent protein fusion
of myosin XI, we found that, during mitosis, this molecule appears to associate
with the kinetochores immediately after nuclear envelope breakdown. Following
metaphase, myosin XI stays associated with the spindle's midzone during the rest
of mitosis, and when the phragmoplast is formed, it concentrates at the cell
plate. Using an actin polymerization inhibitor, latrunculin B, we found that the
association of myosin XI with the mitotic spindle and the phragmoplast are only
partially dependent on the presence of filamentous actin. We also showed that
myosin XI on the spindle partially overlaps with a v-SNARE vesicle marker but is
not co-localized with the endoplasmic reticulum and a RabA vesicle marker. These
observations suggest an actin-dependent and an actin-independent behavior of
myosin XI during cell division, and provide novel insights to our understanding
of the function of myosin XI during plant cell division.
PMID- 29339159
TI - Analysis of the interactions between GMF and Arp2/3 complex in two binding sites
by molecular dynamics simulation.
AB - The Arp2/3 complex plays a key role in nucleating actin filaments branching. The
glia maturation factor (GMF) competes with activators for interacting with the
Arp2/3 complex and initiates the debranching of actin filaments. In this study,
we performed a comparative analysis of interactions between GMF and the Arp2/3
complex and identified new amino acid residues involved in GMF binding to the
Arp2/3 complex at two separate sites, revealed by X-ray and single particle EM
techniques. Using molecular dynamics simulations we demonstrated the quantitative
and qualitative changes in hydrogen bonds upon binding with GMF. We identified
the specific amino acid residues in GMF and Arp2/3 complex that stabilize the
interactions and estimated the mean force profile for the GMF using umbrella
sampling. Phylogenetic and structural analyses of the recently defined GMF
binding site on the Arp3 subunit indicate a new mechanism for Arp2/3 complex
inactivation that involves interactions between the Arp2/3 complex and GMF at two
binding sites.
PMID- 29339160
TI - Overstretching partially alkyne functionalized dsDNA using near infrared optical
tweezers.
AB - The force-extension behaviour of synthesized double-stranded DNAs (dsDNAs)
designed to have 2.1% or 6.6% of the thymine bases alkyne functionalized was
studied using near infrared (NIR) optical tweezers. Measurements were carried out
on substrates with and without flurophores covalently attached to the alkyne
moiety over an extended force range (F=0-70 pN) and results were compared to
those obtained from an unmodified control. In accordance with earlier work [1]
(measured over a force range F=0-5 pN), the force-extension of the dsDNA
containing 2.1% modified-bases agreed well with that of the control. By contrast,
the force-extension of the dsDNA containing 6.6% modified-bases showed an
increasing deviation from that of the control as the dsDNA extension approached
the molecule's contour length. These results indicate that incorporating alkyne
functionalized bases can modify the mechanical properties of the dsDNA and that
degree of functionalization should be carefully considered if a fluorescent
mechanical analogue is required. A discrepancy between 1) the control dsDNA force
extension measured in Ref. [1] and that measured here and 2) dsDNA extensions
carried out on the same duplex at different laser powers was noted; this was
attributed to beam heating by the NIR trapping laser which was estimated to raise
the local temperature at the optical traps by DeltaT~10-15 degrees C.
PMID- 29339162
TI - A method to improve prediction of secondary structure for large single RNA
sequences.
AB - The function of a particular RNA molecule within an organic system is principally
determined by its structure. The current physical methods available for structure
determination are time consuming and expensive. Hence, computational methods for
structure prediction are often used. The prediction of the structure of a large
single sequence of RNA needs a lot of research work. In the present work, a
method is introduced to improve the prediction of large single sequence RNA
secondary structure obtained by Mfold program using the concept of minimum free
energy. The Mfold program contains a constraint option that allows forcing some
helices in the predicted structure. In our method, some of the firstly formed
hairpins that are expected, by a statistical study, to be present in the real
structure are forced in the Mfold predicted structure. The results show
improvement, toward the real structure, in the Mfold predicted structure and this
gives evidence to the RNA kinetic folding.
PMID- 29339161
TI - A new genetically engineered mouse model of choroid plexus carcinoma.
AB - Choroid plexus carcinomas (CPCs) are highly malignant brain tumours predominantly
found in children and associated to poor prognosis. Improved therapy for these
cancers would benefit from the generation of animal models. Here we have created
a novel mouse CPC model by expressing a stabilised form of c-Myc (MycT58A) and
inactivating Trp53 in the choroid plexus of newborn mice. This induced aberrant
proliferation of choroid plexus epithelial cells, leading to aggressive tumour
development and death within 150 days. Choroid plexus tumours occurred with a
complete penetrance in all brain ventricles, with prevalence in the lateral and
fourth ventricles. Histological and cellular analysis indicated that these
tumours were CPCs resembling their human counterparts. Comparison of gene
expression profiles of CPCs and non-neoplastic tissues revealed profound
alterations in cell cycle regulation and DNA damage responses, suggesting that
dysregulation of cell division and DNA checkpoint pathways may represent key
vulnerabilities. This novel animal model of CPC provides an invaluable tool to
elucidate the mechanism of CPC formation and to develop successful therapies
against this devastating paediatric cancer.
PMID- 29339163
TI - Early process development of API applied to poorly water-soluble TBID.
AB - Finding and optimising of synthesis processes for active pharmaceutical
ingredients (API) is time consuming. In the finding phase, established methods
for synthesis, purification and formulation are used to achieve a high purity API
for biological studies. For promising API candidates, this is followed by pre
clinical and clinical studies requiring sufficient quantities of the active
component. Ideally, these should be produced with a process representative for a
later production process and suitable for scaling to production capacity. This
work presents an overview of different approaches for process synthesis based on
an existing lab protocol. This is demonstrated for the production of the model
drug 4,5,6,7-tetrabromo-2-(1H-imidazol-2-yl) isoindolin-1,3-dione (TBID). Early
batch synthesis and purification procedures typically suffer from low and
fluctuating yields and purities due to poor process control. In a first step the
literature synthesis and purification procedure was modified and optimized using
solubility measurements, targeting easier and safer processing for consecutive
studies.
PMID- 29339164
TI - NANOS2 acts as an intrinsic regulator of gonocytes-to-spermatogonia transition in
the murine testes.
AB - In the male mouse embryos, the primordial germ cells colonize the developing
testes at E11.5. These resident germ cells termed gonocytes are the predecessors
of spermatogonial stem cells (SSCs) and differentiating spermatogonia. Both of
which are essential for male fertility where the former maintains the continuity
of spermatogenesis and the latter generates pioneering waves of spermatozoa.
Therefore the timely initiation of gonocytes-to-spermatogonia transition (GST) is
an important process during which the cell fates of gonocytes might be
segregated. However, it is unknown whether gonocytes are composed of a
heterogeneous mixture of germ cells with distinct differentiation potentials
during GST. Here, we find that gonocytes exhibit heterogeneity in terms of the
expression pattern of at least three early spermatogonial marker genes namely
Nanos2, Stra8 and Gfra1. NANOS2 expression levels are negatively correlated with
those of STRA8 and GFRA1 before GST, while positive correlation with GFRA1 is
established after GST. We further find that overexpression of NANOS2 results in
the repression of GFRA1 and PLZF in gonocytes, leading to a delay in GST. On the
other hand, loss of NANOS2 results in the up-regulation of GFRA1 and PLZF,
indicating a precocious entry of GST. Taken together, our data suggest that
NANOS2 functions as an intrinsic timekeeper of GST in the mouse testes.
PMID- 29339165
TI - Safety and Efficacy of Transcatheter Left Atrial Appendage Closure for Stroke
Prevention in Patients with Atrial Fibrillation.
AB - Atrial Fibrillation (AF) is associated with a substantial risk of thromboembolic
stroke. Although long-term treatment with warfarin or the non-vitamin K oral
anticoagulants can reduce this risk, such therapy is underutilized, and safe and
consistent long-term treatment can be challenging. Transcatheter left atrial
appendage (LAA) closure is an emerging alternative to long-term oral
anticoagulation. Long-term follow-up of randomized clinical trials demonstrate
that Watchman LAA closure provides significant reductions in hemorrhagic stroke,
cardiovascular death, and all-cause mortality compared with continued warfarin
therapy. Major bleeding is also reduced compared with continued warfarin therapy
once the post-implant pharmacologic regimen is completed. This review summarizes
the current dataset for the safety and efficacy of transcatheter LAA closure, and
highlights the gaps in evidence and future directions for clinical research.
PMID- 29339166
TI - Anticoagulation in Acute Coronary Syndrome-State of the Art.
AB - Early intravenous anticoagulation is the corner stone treatment of patients
admitted with an acute coronary syndrome: it antagonizes the ongoing coronary
thrombosis and facilitates the percutaneous coronary intervention, hence a
reduction of mortality and acute stent thrombosis. Unfractionated heparin,
enoxaparin, bivalirudin and fondaparinux have been extensively studied in large
randomized control trials and meta-analyses with the same objective: reducing the
ischemic burden without hiking hemorrhagic events. This conundrum is evolving
along the generalization of the radial-artery access, the use of potent P2Y12 and
the trend towards a tailored approach regarding the ischemic and bleeding
balance. In this systematic review, we aimed at presenting the evidence based
data and strategies for each anticoagulant in the setting of acute coronary
syndrome with and without ST-segment elevation.
PMID- 29339167
TI - Comparison of Anticoagulant Therapy for Atrial Fibrillation - Novel Oral
Anticoagulants Versus Vitamin K Antagonists.
AB - In patients with non-valvular atrial fibrillation (NVAF), oral anticoagulation is
important for prevention of stroke and systemic embolism (SE). While Vitamin K
antagonists (VKAs) have historically been the standard of care, these medications
are limited by numerous food and drug interactions with onerous requirements for
frequent monitoring and dose adjustments. Over the past decade, several novel
oral anticoagulants (NOACs) have been developed to directly inhibit factor
IIa/thrombin (dabigatran) or activated factor X (apixaban, rivaroxaban,
edoxaban). These medications have been shown to be at least as effective as
warfarin for stroke prevention in NVAF with more favorable safety profiles.
However, their advantages are underscored by a lack of specific antidotes and
assays quantifying their anticoagulant effects. This paper addresses the use of
NOACs compared to VKAs in patients with NVAF, with a special focus on high-risk
populations, including the elderly, those with renal disease, diabetes mellitus,
coronary artery disease, and previous stroke. The current literature surrounding
special clinical scenarios including the treatment of bleeding, perioperative
management, and the use of NOACs in cardioversion and catheter ablation will be
also discussed.
PMID- 29339168
TI - Selection of P2Y12 Inhibitor in Percutaneous Coronary Intervention and/or Acute
Coronary Syndrome.
AB - The P2Y12 receptor plays a critical role in the amplification of platelet
aggregation in response to various agonists and stable thrombus generation at the
site of vascular injury leading to deleterious ischemic complications. Therefore,
treatment with a P2Y12 receptor blocker is a major effective strategy to prevent
ischemic complications in high-risk patients with acute coronary syndrome (ACS)
and patients undergoing percutaneous coronary intervention (PCI). The
determination of optimal platelet inhibition is based on maximizing
antithrombotic properties while minimizing bleeding risk and is critically
dependent on individual patient's propensity for thrombotic and bleeding risks.
Immediately after ACS and during PCI, where highly elevated thrombotic activity
is present, a loading dose administration with a potent P2Y12 receptor blocker
such as ticagrelor or prasugrel is preferred. In stable coronary artery disease
patients undergoing PCI, clopidogrel is widely used. In addition, in patients
with ST-segment elevation myocardial infraction who cannot take oral medications,
a fast acting intravenous glycoprotein IIb/IIIa inhibitor or P2Y12 receptor
blocker, cangrelor, may add clinical benefits. During long term therapy, a
strategy that prevents ischemic risk while avoiding excessive bleeding risk is
similarly desired. Although up to one year dual antiplatelet therapy (DAPT) is
recommended in patients undergoing elective stenting, the available data support
the anti-ischemic benefit of prolonged DAPT (more than1 year) in patients with
prior MI. In addition to the DAPT risk calculator tool, future risk assessment
methods that analyze intrinsic thrombogenicity and atherosclerotic coronary
burden may further identify the optimal candidate for prolonged DAPT to improve
net clinical outcomes.
PMID- 29339169
TI - The Timing of P2Y12 Inhibitor Initiation in the Treatment of ACS? Does the
Evidence Exist in This Era?
AB - The majority of acute coronary syndromes (ACS) are well characterized as a
consequence of plaque rupture and subsequent thrombosis. Antiplatelet agents
targeting inhibition of P2Y12 receptors on the platelets have been shown to
reduce future risk of cardiovascular events in this patient population. However,
the timing of initiation of these agents, in particular, in patients managed with
an invasive strategy with percutaneous coronary interventions (PCI) is debatable.
The data supporting pretreatment with antiplatelet agents prior to PCI in ACS
patients date to trials performed >15 years ago, wherein the time to PCI was >5
days, and hence, the utility of pretreatment with these agents in the
contemporary era remains uncertain. In addition, newer antiplatelet agents such
as prasugrel, ticagrelor, and cangrelor with rapid onset of action, pose a
challenge for justification of oral antiplatelet pretreatment in patients with
ACS. In this review article, we will discuss the pharmacokinetic properties of
four different antiplatelet agents (clopidogrel, prasugrel, ticagrelor,
cangrelor), as well as major randomized clinical trials assessing safety and
efficacy of their role as pretreatment agents in patients presenting with ACS.
PMID- 29339170
TI - Sub-anesthetic doses of ketamine attenuate nicotine self-administration in rats.
AB - Smoking cessation strategies are of prime medical importance. Despite
availability of various pharmacological agents in combating addiction to
nicotine, more effective medications are needed. Based on recent findings, the
glutamatergic system in the brain may provide novel targets. Here, we evaluated
the effects of acute administration of sub-anesthetic doses of ketamine, an NMDA
receptor antagonist, in both male and female Sprague-Dawley rats trained to self
administer nicotine. Animals were injected subcutaneously with 5, 7.5 and 10
mg/kg ketamine or saline and the effects on the number of intravenous nicotine
infusions during a 45 min session was measured. Ketamine treatment significantly
reduced nicotine self-administration in a dose-dependent manner. Moreover, a
differential sensitivity between the sexes was observed as male rats responded to
a lower dose of ketamine and with higher magnitude of effect than female rats. It
is concluded that glutamatergic receptor manipulations may offer a novel and
potentially sex-dependent intervention in nicotine addiction.
PMID- 29339171
TI - DNA methylation level of the neprilysin promoter in Alzheimer's disease brains.
AB - Neprilysin (NEP), a membrane-bound metalloprotease, has been shown to play an
essential role in the clearance of amyloid beta (Abeta) peptides. Previous
studies have reported that NEP expression is downregulated in the normal aging
brain as well as in the Alzheimer's disease (AD) brain, providing evidence that
the downregulation of NEP expression contributes to the age-dependent deposition
of Abeta-containing plaques, a pathological hallmark of AD. However, the
mechanisms underlying the downregulation remain unclear. In this study, we
explored the relationship between DNA methylation status of CpG islands in the
NEP promoter and its expression level in AD brains. We performed pyrosequencing
analyses to detect the DNA methylation level in 31 postmortem AD brains and 40
normal control brains. All 30 CpG sites showed no clear difference in methylation
level. To further focus on methylation changes specific to neuronal cells, we
performed methylation array experiments using neuronal nuclei from postmortem
brains and found no clear difference in the methylation level between AD and
normal control samples. Our detailed analyses, with a substantial number of brain
samples, provide the first convincing evidence that DNA methylation of the NEP
promoter is not involved in AD development and progression.
PMID- 29339172
TI - Self-relevant processing of stranger's name in Chinese society: Surname matters.
AB - Stimuli that have been frequently used to induce self-relevant processing are
highly familiar to individuals (e.g., self-name [SN] and self-face). One's
surname is an important form of collective self-concept; it represents the line
of ancestry, and is psychologically salient. According to this concept, a
stranger with the same surname may also elicit salient self-relevant processing,
despite unfamiliarity; however, this has not yet been directly investigated. The
present study adopted a three-stimulus oddball paradigm and multimodal
electroencephalography to study the potential self-relevant processing of such
stimuli. Behavioral results indicated that same-surname unfamiliar (SSU) names
were rated more self-relevant than different-surname unfamiliar (DSU) names,
although they were rated equally unfamiliar to subjects. Analysis of EEG data
showed similar P2 enhancement in response to SN and SSU when compared to DSU. In
contrast, the self-relevant effect on P3 amplitudes and theta synchronization
decreased linearly from SN, SSU, to DSU conditions. Thus, both the behavioral and
electrophysiological data indicate that unfamiliar names with the same surname
can evoke reliable self-relevant processing.
PMID- 29339173
TI - Neuroprotective effects of topiramate and memantine in combination with
hypothermia in hypoxic-ischemic brain injury in vitro and in vivo.
AB - Hypoxic-ischemic encephalopathy (HIE) is a major cause of perinatal mortality and
subsequent severe neurological sequelae. Mild hypothermia is a standard therapy
for HIE, but is used only in selected Reference Centers and in neonates >1800 g.
Since neuronal death following HIE occurs by a cascade of events triggered by
activation of glutamate receptors, we used in vitro and in vivo models of HIE to
examine whether the AMPA/kainate receptor antagonist topiramate and the NMDA
receptor antagonist memantine could exert neuroprotective effects, alone or in
combination with hypothermia. For the in vitro experiments, rat organotypic
hippocampal slices were exposed to a 30 min duration of oxygen-glucose
deprivation (OGD): treatment with topiramate (1 MUM) and memantine (10-30 MUM) or
hypothermia (35 degrees C or 32 degrees C) significantly attenuated CA1 damage
after 24 h. The combination of hypothermia with topiramate and memantine enhanced
their protective effect. For the in vivo experiments, we used 7 day-old rat pups
subjected to permanent left common carotid artery occlusion followed by 120 min
of hypoxia. Administration of topiramate or memantine (i.p., 20 mg/kg)
immediately and 2 h after hypoxia or exposure to hypothermia (32 degrees C for 4
h beginning 1 h after hypoxia) significantly reduced the extent of the resulting
infarct. The combination of topiramate or memantine with hypothermia elicited a
reduction of the infarct that was greater than that produced by drugs or
hypothermia alone. Notably, memantine displayed a higher degree of
neuroprotection as compared to topiramate both in vitro and in vivo and, when
used alone at 20 mg/kg in vivo, produced a greater reduction in brain damage than
observed using topiramate in combination with hypothermia. These results suggest
that memantine may be more advantageous than topiramate as a therapeutic agent in
neonates with HIE treated with hypothermia.
PMID- 29339174
TI - The impact of strabismus surgery on gait pattern in patients with congenital or
starting within one year of age strabismus.
AB - Strabismus is a common visual disorder that negatively affects walking and
balance. Therapeutic interventions for strabismus include strabismus surgery. Few
studies investigated the relationship between strabismus surgery and postural
control while, to the best of our knowledge, none has been conducted to assess
the influence of strabismus surgery on gait. Therefore, the aim of this study was
to evaluate the locomotion characteristics over patients with congenital or
starting within one year of age strabismus, one month and three months after
strabismus surgery. We enrolled 17 patients with a number of motor and sensorial
features. Patients underwent an orthoptic and ophthalmological evaluation as well
as a biomechanical evaluation before (T0) and after strabismus surgery (T1 at 1
month, and T2 at 3 months). We observed, mostly in T2 evaluation, significant
improvements in the spatio-temporal parameters, such as cadence, velocity, swing,
stance and double support phases, step and stride length. The kinematic results
revealed a significant increase in hip ROM, strongly related to the improvement
of gait speed. No significant differences has been observed in knee and ankle
joint ROM. The kinetic results revealed a significant increase in the maximum
moment at the knee and ankle joints associated with an increase in the maximum
ankle power. Our findings suggest that the safety and balance control associated
with gait improve in patients with strabismus following surgery.
PMID- 29339175
TI - Primary thymic adenocarcinomas: a clinicopathological and immunohistochemical
study of 16 cases with emphasis on the morphological spectrum of differentiation.
AB - Sixteen cases of primary thymic adenocarcinoma are presented. The patients are 9
men and 7 women between the ages of 22 and 68 years (average, 45 years) who
presented with non-specific symptoms including cough, chest pain, and dyspnea.
Diagnostic imaging revealed the presence of an anterior mediastinal mass, which
was surgically removed in all of the patients. Histologically, none of the tumors
was encapsulated and showed different growth patterns including mucinous, non
mucinous, and papillary features. The majority of cases showed mixed growth
pattern, and the tumor was limited to the mediastinum with only a few cases
extending to lymph nodes or pericardium. In two cases, the adenocarcinoma was
associated with a thymoma. Immunohistochemical stains were performed, and their
positive staining varied depending on the histology of the tumors, showing
positive staining in some cases for keratin 7, keratin 20, CEA, CD5, CD117, and
CDX-2. PAX8 and TTF-1 were negative in all the tumors. Follow-up information was
obtained in 10 patients over a period of 1 to 12 years, indicating that three
patients had died within a period of 14 months, one with brain metastasis, while
seven patients have remained alive without recurrence. The cases herein described
span the spectrum of thymic epithelial tumors and highlight the importance of
recognizing this particular type of carcinoma, as it may follow a different
outcome and require different treatment options.
PMID- 29339176
TI - The absence of class III beta-tubulin is predictive of a favorable response to
nab-paclitaxel and gemcitabine in patients with unresectable pancreatic ductal
adenocarcinoma.
AB - The combined administration of nab-paclitaxel and gemcitabine (nab-P + Gem) is a
standard chemotherapy for unresectable pancreatic ductal adenocarcinoma (UR
PDAC); thus, a predictive biomarker to identify patients best suited for nab-P +
Gem therapy would be useful. Class III beta-tubulin (TUBB3) has been reported to
be a predictive marker for taxane resistance in various tumors. However, the
correlation between TUBB3 expression and the response to nab-P + Gem in patients
with UR-PDAC has not been evaluated. We retrospectively reviewed 75 patients with
UR-PDAC who received nab-P + Gem. TUBB3 expression was examined
immunohistochemically in specimens obtained by endoscopic ultrasound-guided fine
needle aspiration (EUS-FNA). From 67 analyzable specimens that were available for
TUBB3 staining, 14 (21%) were negative for TUBB3 immunostaining and 53 (79%) were
positive. Patients with negative TUBB3 expression showed a significantly higher
disease control rate (100% vs. 64.2%; P = .008) and longer progression-free
survival (PFS); (7.1 months vs. 3.7 months; log-rank test, P = .036) than those
of patients with positive. Furthermore, negative TUBB3 expression was an
independent predictive marker of a prolonged PFS on multivariate analysis (hazard
ratio, 2.41; 95% confidence interval, 1.11-5.24; P = .026). Our data indicate
that an absence of TUBB3 expression in specimens obtained by EUS-FNA may be a
favorable predictive marker of the response to nab-P + Gem in patients with UR
PDAC, highlighting its use as a potential new biomarker for treatment
optimization.
PMID- 29339177
TI - Trends in reporting histological subtyping of renal cell carcinoma: association
with cancer center type.
AB - Histological classification of renal cell carcinoma (RCC) has become increasingly
important for clinical management. We identified 295483 RCC diagnosed from 1998
2014 in the National Cancer Database (NCDB) to examine temporal trends in
proportions of RCC with unspecified histology and several specific histologies
from the 1998 and 2004 World Health Organization classifications of RCC. Further,
multivariable log binomial analysis of 101062 RCC diagnosed from 2010 to 2014 was
used to determine whether the association of diagnosing/treating facility type
and the proportion of unspecified RCC is independent of patient demographic and
clinical factors. Between 1998 and 2014, the proportion of histologically
unspecified RCC decreased substantially in all facility types, with the decrease
smallest in community programs (from 86.0% to 28.1%) and largest in National
Cancer Institute-designated centers (from 85.1% to 9.8%). These decreases were
offset by increases in percentages of papillary, clear cell, and chromophobe RCC
cases. During 2010 to 2014, relative to community programs, RCCs were 21% less
likely to be reported as unspecified histology (adjusted prevalence ratio [aPR] =
0.79; 95% CI, 0.68-0.92) in comprehensive community programs, 32% less likely in
integrated network programs (aPR = 0.68; 95% CI, 0.57-0.92) and academic programs
(aPR = 0.68; 95% CI, 0.54-0.87), and 63% less likely (aPR = 0.37; 95% CI, 0.26
0.52) in National Cancer Institute -designated programs. These results have
implications for the optimal selection of targeted systemic therapies for
patients with advanced disease, and for the potential value of cancer registry
data in pathology quality improvement programs to promote more rapid and
consistent adoption of new classifications of RCC and other neoplasms.
PMID- 29339178
TI - The evolving diagnosis of noninvasive follicular thyroid neoplasm with papillary
like nuclear features (NIFTP).
PMID- 29339179
TI - Primary diffuse leptomeningeal atypical teratoid/rhabdoid tumor diagnosed by
cerebrospinal fluid cytology: case report with molecular genetic analysis.
AB - Atypical teratoid/rhabdoid tumors (AT/RT) are rare malignant neoplasms that
mainly affect infants and young children, and are typically located in the
cerebellar hemispheres. These tumors are histologically characterized by varying
proportions of rhabdoid cells, and nuclear INI1 immunonegativity. Here, we report
a case of a 15-year-old male with primary diffuse leptomeningeal AT/RT. The
patient had symptoms similar to those of meningitis. Magnetic resonance imaging
revealed leptomeningeal thickening. Cytological examination using cerebrospinal
fluid was repeatedly performed and revealed rhabdoid cells with loss of INI1
reactivity, and shortly after, the diagnosis of AT/RT was confirmed by tissue
biopsy. Multiplex ligation-dependent probe amplification analysis revealed
compound heterozygous microdeletion of the SMARCB1/INI1 locus. Leptomeningeal
AT/RT without primary mass is extremely rare - only four cases have been
previously reported to date. To the best of our knowledge, this is the first case
report of primary leptomeningeal AT/RT with detailed genetic information.
PMID- 29339180
TI - Leptin blocks the inhibitory effect of vitamin D on adipogenesis and cell
proliferation in 3T3-L1 adipocytes.
AB - Recently, we demonstrated high serum leptin and 25(OH)D (calcidiol) in obese
animals, with high C/EBPbeta and PPARgamma expression in adipose tissue. Since
the role of vitamin D in adipogenesis remains controversial and hyperleptinemia
is found in obesity, we asked if leptin could interfere in vitamin D action on
adipocytes. Here, we studied the direct effect of these two hormones upon 3T3L1
preadipocytes incubated with or without 1,25(OH)2D (100 nM, 24 h) and with leptin
(10-7 M, 4 h later). RT-PCR (VDR and Cyp27b1/1alpha-hydroxylase), western
blotting (VDR, Cyp27b1/1alpha-hydroxylase, ObR-b, C/EBPbeta, PPARgamma and Bax
content), a cell proliferation assay and an Annexin V-FITC binding assay were
performed. Incubation with 1,25(OH)2D decreased Cyp27b1/1alpha-hydroxylase and
VDR. Co-incubation of 1,25(OH)2D and leptin did not change Cyp27b1/1alpha
hydroxylase and had no additive effect upon the decreased VDR mRNA. Incubation
with 1,25(OH)2D decreased C/EBPbeta and PPARgamma. In the cell proliferation
assay, 1,25(OH)2D decreased the number of 3T3L1 cells. No changes in OBR-b or
apoptotic parameters (Bax and annexin-V) were observed. The 1,25(OH)2D decreased
pro-adipogenic factors and proliferation of adipocytes. However, since it
inhibits the conversion of 25(OH)D to 1,25(OH)2D and VDR mRNA long-term, it could
decrease the vitamin D response in adipocytes, leading to greater adipogenesis.
The co-incubation of both hormones, simulating what occurs in obesity, even
neutralizing the effect on Cyp27b1/1alpha-hydroxylase, did not change the vitamin
D sensitivity but decreased SOCS-3 and pSTAT-3. Thus, an excess of vitamin D and
hyperleptinemia could decrease vitamin D sensitivity in adipocytes, contributing
to increased adipogenesis.
PMID- 29339181
TI - Effects of age on growth in Atlantic bluefin tuna (Thunnus thynnus).
AB - Atlantic Bluefin Tuna Thunnus thynnus (ABFT) is considered one of the most
important socio-economic species but there is a lack of information on the
physiological and molecular processes regulating its growth and metabolism. In
the present study, we focused on key molecules involved in growth process. The
aim of the present study was to associate molecular markers related to growth
with canonical procedures like morphological measurements such as curved fork
length (CFL) and round weight (RWT). The ABFT specimens (n = 41) were organized
into three different groups A, B and C according to their age. The molecular
analysis of liver samples revealed that igf1, igf1r and mTOR genes, involved in
growth process, were differentially expressed in relation to the age of the fish.
In addition, during the analyzed period, faster growth was evident from 5 to 8
years of age, after that, the growth rate decreased in terms of length yet
increased in terms of adipose tissue storage, as supported by the higher fat
content in the liver. These results are useful in expanding basic knowledge about
the metabolic system of ABFT and provide new knowledge for the aquaculture
industry.
PMID- 29339182
TI - Interrelationship among annual cycles of sex steroids, corticosterone and body
condition in Nyctibatrachus humayuni.
AB - Synergism between extrinsic and intrinsic factors is crucial for the seasonality
of reproduction. Environmental factors such as photoperiod and temperature
activate the hypothalamus-pituitary-gonadal axis leading to the secretion of
steroid hormones that are crucial for reproduction. Sex steroids are not only
essential for the maturation of gonads, but also for development of secondary
sexual characters in males and reproductive behaviour of both the sexes. In the
present study, we quantified the urinary testosterone (UTM) and corticosterone
(UCM) metabolites in males and urinary estradiol metabolites (UEM) and UCM in
females of Nyctibatrachus humayuni for two consecutive years to determine annual
and seasonal variation in the levels of sex steroids, corticosterone and body
condition index (BCI). The results show that sex steroids were highest during the
breeding season and lowest during the non-breeding season in both the sexes. An
increase in UTM and UEM was observed in males and females respectively during the
breeding season. Testicular histology showed the presence of all stages of
spermatogenesis throughout the year indicating that spermatogenesis is
potentially continuous. Ovarian histology showed the presence of vitellogenic
follicles only during the breeding season indicating that oogenesis is strictly
seasonal. In males, UCM levels were highest during the breeding season, while in
females their levels were highest just prior to the breeding season. In males,
BCI was highest during the pre-breeding season, declined during the breeding
season to increase again during the post-breeding season. In females, BCI was
comparable throughout the year. In males, UTM levels were positively correlated
with UCM levels but negatively correlated with BCI. Interestingly, UEM, UCM and
BCI were not correlated in females. These results indicate that N. humayuni
exhibits an associated pattern of reproduction. Quantification of urinary
progesterone metabolites (UPM) during the breeding season showed UPM levels were
higher in post-spawning females, suggesting the significance of progesterone in
ovulation. Further, non-invasive enzyme immunoassay has been successfully
standardized in N. humayuni for the quantification of urinary metabolites of
steroid hormones.
PMID- 29339183
TI - Evolution of the growth hormone, prolactin, prolactin 2 and somatolactin family.
AB - Growth hormone (GH), prolactin (PRL), prolactin 2 (PRL2) and somatolactin (SL)
belong to the same hormone family and have a wide repertoire of effects including
development, osmoregulation, metabolism and stimulation of growth. Both the
hormone and the receptor family have been proposed to have expanded by gene
duplications in early vertebrate evolution. A key question is how hormone
receptor preferences have arisen among the duplicates. The first step to address
this is to determine the time window for these duplications. Specifically, we
aimed to see if duplications resulted from the two basal vertebrate
tetraploidizations (1R and 2R). GH family genes from a broad range of vertebrate
genomes were investigated using a combination of sequence-based phylogenetic
analyses and comparisons of synteny. We conclude that the PRL and PRL2 genes
arose from a common ancestor in 1R/2R, as shown by neighboring gene families. No
other gene duplicates were preserved from these tetraploidization events. The
ancestral genes that would give rise to GH and PRL/PRL2 arose from an earlier
duplication; most likely a local gene duplication as they are syntenic in several
species. Likewise, some evidence suggests that SL arose from a local duplication
of an ancestral GH/SL gene in the same time window, explaining the lack of
similarity in chromosomal neighbors to GH, PRL or PRL2. Thus, the basic triplet
of ancestral GH, PRL/PRL2 and SL genes appear to be unexpectedly ancient.
Following 1R/2R, only SL was duplicated in the teleost-specific tetraploidization
3R, resulting in SLa and SLb. These time windows contrast with our recent report
that the corresponding receptor genes GHR and PRLR arose through a local
duplication in jawed vertebrates and that both receptor genes duplicated further
in 3R, which reveals a surprising asynchrony in hormone and receptor gene
duplications.
PMID- 29339184
TI - A novel stress hormone response gene in tadpoles of Xenopus tropicalis.
AB - Previous work identified a transcribed locus, Str. 34945, induced by the frog
stress hormone corticosterone (CORT) in Xenopus tropicalis tails. Because thyroid
hormone had no influence on its expression, Str. 34945 was dubbed the first "CORT
only" gene known from tadpoles. Here, we examine the genomic annotation for this
transcript, hormone specificity, time course of induction, tissue distribution,
and developmental expression profile. The location of Str. 34945 on the X.
tropicalis genome lies between the genes ush1g (Usher syndrome 1G) and fads6
(fatty acid desaturase 6). A blast search showed that it maps to the same region
on the X. laevis genome, but no hits were found in the human genome. Using RNA
seq data and conventional reverse transcriptase PCR and sequencing, we show that
Str. 34945 is part of the 3' untranslated region of ush1g. We find that CORT but
not aldosterone or thyroid hormone treatment induces Str. 34945 in tadpole tails
and that expression of Str. 34945 achieves maximal expression within 12-24 h of
CORT treatment. Among tissues, Str. 34945 is induced to the highest degree in
tail, with lesser induction in lungs, liver, and heart, and no induction in the
brain or kidney. During natural metamorphosis, Str. 34945 expression in tails
peaks at metamorphic climax. The role of ush1g in metamorphosis is not
understood, but the specificity of its hormone response and its expression in
tail make ush1g valuable as a marker of CORT-response gene induction independent
of thyroid hormone.
PMID- 29339185
TI - Dose-response relationship of tryptophan with large neutral amino acids, and its
impact on physiological responses in the chick model.
AB - Tryptophan (Trp) has been associated with the regulation of several behavioral
and physiological processes, through stimulation of serotonergic activity.
Tryptophan utilization at the metabolic level is influenced by the competitive
carrier system it shares with large neutral amino acids (LNAA). This study was
carried out using meat-type chicken as a model, to investigate the dose response
effects of Trp/LNAA on fear response (tonic immobility; TI) and hormonal
responses, including corticosterone (CORT), serotonin (5-HT), triiodothyronine
(T3) and thyroxine (T4). A total of 12 cages (48 birds) were assigned to each of
the six experimental groups at 29-42 days of age. Experimental diets were
formulated to have incremental levels of Trp/LNAA (0.025, 0.030, 0.035, 0.040,
0.045, and 0.050). The results revealed that, Trp/NAA had no significant effect
on growth performance and TI of the birds. However, elevation of Trp/LNAA was
concurred with a linear reduction in CORT (P < .0001, r2 = 0.819) and linear
increases in 5-HT (P < .0001, r2 = 0.945), T3 (P = .0003, r2 = 0.403) and T4 (P <
.0001, r2 = 0.937) levels. In conclusion, the results from the current study
demonstrated that, although incremental levels of Trp/LNAA did not affect bird
growth performance or fearfulness, it increased 5-HT, T3 and T4, and decreased
CORT levels in a linear dose-dependent manner. Manipulation of Trp feeding levels
could be applied to manage stressful conditions in birds.
PMID- 29339186
TI - Uptake and intracellular fate of cholera toxin subunit b-modified mesoporous
silica nanoparticle-supported lipid bilayers (aka protocells) in motoneurons.
AB - Cholera toxin B (CTB) modified mesoporous silica nanoparticle supported lipid
bilayers (CTB-protocells) are a promising, customizable approach for targeting
therapeutic cargo to motoneurons. In the present study, the endocytic mechanism
and intracellular fate of CTB-protocells in motoneurons were examined to provide
information for the development of therapeutic application and cargo delivery.
Pharmacological inhibitors elucidated CTB-protocells endocytosis to be dependent
on the integrity of lipid rafts and macropinocytosis. Using immunofluorescence
techniques, live confocal and transmission electron microscopy, CTB-protocells
were primarily found in the cytosol, membrane lipid domains and Golgi. There was
no difference in the amount of motoneuron activity dependent uptake of CTB
protocells in neuromuscular junctions, consistent with clathrin activation at the
axon terminals during low frequency activity. In conclusion, CTB-protocells
uptake is mediated principally by lipid rafts and macropinocytosis. Once
internalized, CTB-protocells escape lysosomal degradation, and engage biological
pathways that are not readily accessible by untargeted delivery methods.
PMID- 29339187
TI - Doxorubicin-loaded dendritic-Fe3O4 supramolecular nanoparticles for magnetic drug
targeting and tumor regression in spheroid murine melanoma model.
AB - This work evaluates the magnetically-guided delivery of DOX-loaded dendritic
Fe3O4 nanoparticles and their tumor regression efficacy in subcutaneous melanoma
in C57BL/6 mice. The hematological, biochemical and histopathological parameters
were minimally affected. The nanoparticles localized in lungs, liver and spleen
suggesting non-specific uptake. However, in tumor-bearing mice, substantially
higher localization in magnetically-targeted tumor was observed when compared to
passive localization in non-targeted tumor. The animals of treated group showed
significantly high iron levels (161 MUg of Fe/mg dry organ weight) in the tumor
against the control (<25 MUg of Fe/mg dry organ weight). This high localization
led to high concentrations of DOX in the tumor which not only induced significant
tumor regression but also arrested further growth. Within 14 days, the average
tumor volume was reduced to 55+/-8.3 mm3 (treated) as compared to 4794+/-844 mm3
(control), i.e. ~88-fold decrease. The tumor disappeared by the end of 20th day
post-treatment and ~100% survival rate was observed.
PMID- 29339188
TI - The enhancement of siPLK1 penetration across BBB and its anti glioblastoma
activity in vivo by magnet and transferrin co-modified nanoparticle.
AB - In order to enhance the penetration of small interference RNA against the polo
like kinase I (siPLK1) across BBB to treat glioblastoma (GBM), transferrin (Tf)
modified magnetic nanoparticle (Tf-PEG-PLL/MNP@siPLK1) was prepared. The in vitro
experiments indicated that Tf-PEG-PLL/MNP@siPLK1 enhanced the cellular uptake of
siPLK1, which resulted in an increase of gene silencing effect and cytotoxicity
of Tf-PEG-PLL/MNP@siPLK1 on U87 cells. Besides, Tf-PEG-PLL/MNP@siPLK1
significantly inhibited the growth of U87 glioblastoma spheroids and markedly
increased the BBB penetration efficiency of siPLK1 with the application of
external magnetic field in in-vitro BBB model. The in vivo experiments indicated
that siPLK1 selectively accumulated in the brain tissue, and markedly reduced
tumor volume and prolonged the survival time of GBM-bearing mice after Tf-PEG
PLL/MNP@siPLK1 was injected to GBM-bearing mice via tail vein. The above data
indicated that magnet and transferrin co-modified nanoparticle enhanced siPLK1
penetration across BBB and increased its anti GBM activity in vivo.
PMID- 29339189
TI - Magnetic nanoparticles modified-porous scaffolds for bone regeneration and
photothermal therapy against tumors.
AB - For effectively treating tumor related-bone defects, design and fabrication of
multifunctional biomaterials still remain a great challenge. Herein, we firstly
fabricated magnetic SrFe12O19 nanoparticles modified-mesoporous bioglass
(BG)/chitosan (CS) porous scaffold (MBCS) with excellent bone regeneration and
antitumor function. The as-produced magnetic field from MBCS promoted the
expression levels of osteogenic-related genes (OCN, COL1, Runx2 and ALP) and the
new bone regeneration by activated BMP-2/Smad/Runx2 pathway. Moreover, the
SrFe12O19 nanoparticles in MBCS improved the photothermal conversion property.
Under the irradiation of near-infrared (NIR) laser, the elevated temperatures of
tumors co-cultured with MBCS triggered tumor apoptosis and ablation. As compared
with the pure scaffold group, MBCS/NIR group possessed the excellent antitumor
efficacy against osteosarcoma via the hyperthermia ablation. Therefore, the
multifunctional MBCS with excellent bone regeneration and photothermal therapy
functions has a great application for treating the tumor-related bone defects.
PMID- 29339191
TI - Current status and perspectives of fungal entomopathogens used for microbial
control of arthropod pests in Brazil.
AB - Entomopathogenic fungi play a central role in Brazil's biopesticide market.
Approximately 50% of registered microbial biopesticides comprise mycoinsecticides
and/or mycoacaricides consisting of hypocrealean fungi, with most based on
Metarhizium anisopliae sensu stricto (s. str.) and Beauveria bassiana s. str.
These fungi are mainly used to control spittlebugs in sugarcane fields and
whiteflies in row crops, respectively, with annual applications surpassing three
million hectares. Research also emphasizes the potential of fungal
entomopathogens to manage arthropod vectors of human diseases. Most registered
fungal formulations comprise wettable powders or technical (non-formulated)
products, with relatively few new developments in formulation technology. Despite
the large area treated with mycoinsecticides (i.e., approx. 2 million ha of
sugarcane treated with M. anisopliae and 1.5 million ha of soybean treated with
B. bassiana), their market share remains small compared with the chemical
insecticide market. Nevertheless, several major agricultural companies are
investing in fungus-based products with the aim at achieving more sustainable IPM
programs for major pests in both organic and conventional crops. Government and
private research groups are pursuing innovative technologies for mass production,
formulation, product stability and quality control, which will support cost
effective commercial mycoinsecticides. Here, we summarize the status of
mycoinsecticides currently available in Brazil and discuss future prospects.
PMID- 29339192
TI - Tissue specific differences in mitochondrial DNA maintenance and expression.
AB - The different cell types of multicellular organisms have specialized
physiological requirements, affecting also their mitochondrial energy production
and metabolism. The genome of mitochondria is essential for mitochondrial
oxidative phosphorylation (OXHPOS) and thus plays a central role in many human
mitochondrial pathologies. Disorders affecting mitochondrial DNA (mtDNA)
maintenance are typically resulting in a tissue-specific pattern of mtDNA
deletions and rearrangements. Despite this role in disease as well as a biomarker
of mitochondrial biogenesis, the tissue-specific parameters of mitochondrial DNA
maintenance have been virtually unexplored. In the presented study, we
investigated mtDNA replication, topology, gene expression and damage in six
different tissues of adult mice and sought to correlate these with the levels of
known protein factors involved in mtDNA replication and transcription. Our
results show that while liver and kidney cells replicate their mtDNA using the
asynchronous mechanism known from cultured cells, tissues with high OXPHOS
activity, such as heart, brain, skeletal muscle and brown fat, employ a strand
coupled replication mode, combined with increased levels of recombination. The
strand-coupled replication mode correlated also with mtDNA damage levels,
indicating that the replication mechanism represents a tissue-specific strategy
to deal with intrinsic oxidative stress. While the preferred replication mode did
not correlate with mtDNA transcription or the levels of most known mtDNA
maintenance proteins, mtSSB was most abundant in tissues using strand
asynchronous mechanism. Although mitochondrial transcripts were most abundant in
tissues with high metabolic rate, the mtDNA copy number per tissue mass was
remarkably similar in all tissues. We propose that the tissue-specific features
of mtDNA maintenance are primarily driven by the intrinsic reactive oxygen
species exposure, mediated by DNA repair factors, whose identity remains to be
elucidated.
PMID- 29339193
TI - A pilot study on the biomechanical assessment of obstructive sleep apnea pre and
post bariatric surgery.
AB - Obesity is a major risk factor for obstructive sleep apnea patients. In obese
patients the severity of this risk can be reduced by bariatric surgery. This
pilot study investigates the perioperative effects of bariatric surgery on
obstructive sleep apnea and on the physical and biomechanical characteristics of
the upper airway. Polysomnography and computer tomography data for 10 morbid
obese patients promoted for bariatric surgery were conducted before surgery and
at 6 and 12 months postoperatively for assessment of the oropharyngeal anatomy,
and subsequent three-dimensional modelling of the airway. Mean values for the
apnea/hypopnea index and body mass index significantly reduced after surgery. To
combine the effect of changes in the upper airway volume and body mass index, a
new volume body mass index is introduced. This index increases with a successful
bariatric surgery. Although bariatric surgery leads to an effective weight
reduction for all age groups, for obstructive sleep apnea patients it may be
effective for middle age, less effective for 50-60 years, and further less
effective for patients over the age of 60 years.
PMID- 29339190
TI - Systemic and local toxicity of metal debris released from hip prostheses: A
review of experimental approaches.
AB - Despite the technological improvements in orthopedic joint replacement implants,
wear and corrosion products associated with the metal components of these
implants may result in adverse local tissue and perhaps systemic reactions and
toxicities. The current review encompasses a literature review of the local and
systemic toxicity studies concerning the effect of CoCrMo wear debris released
from wear and corrosion of orthopedic implants and prostheses. Release of
metallic debris is mainly in the form of micro- and nano-particles, ions of
different valences, and oxides composed of Co and Cr. Though these substances
alter human biology, their direct effects of these substances on specific tissue
types remain poorly understood. This may partially be the consequence of the
multivariate research methodologies employed, leading to inconsistent reports.
This review proposes the importance of developing new and more appropriate in
vitro methodologies to study the cellular responses and toxicity mediated by
joint replacement wear debris in-vivo.
PMID- 29339195
TI - All about the caspase-dependent functions without cell death.
PMID- 29339194
TI - Vaginal Construction and Treatment Providers' Experiences: A Qualitative
Analysis.
AB - STUDY OBJECTIVE: To investigate specialist clinicians' experiences of treating
vaginal agenesis. DESIGN: Semi-structured interviews. SETTING: Twelve hospitals
in Britain and Sweden. PARTICIPANTS: Thirty-two health professionals connected to
multidisciplinary teams (MDTs) including medical specialists and psychologists.
INTERVENTIONS AND MAIN OUTCOME MEASURES: Theoretical thematic analysis of
recorded verbatim data. RESULTS: The gynecologist and psychologist interviewees
share certain observations including the importance of psychological readiness
for and appropriate timing of treatment. Three overlapping themes are identified
in our theoretical analysis of the MDT clinicians' talk: (1) the stigma of
vaginal agenesis and the pressure to be "normal" can lead patients to minimize
the time, effort, physical discomfort, and emotional cost inherent in treatment.
(2) Under pressure, treatment might be presented to patients with insufficient
attention to the potential psychological effect of the language used.
Furthermore, the opportunity to question what is "normal" in sex is generally not
taken up. It can be challenging to help the women to transcend their medicalized
experiences to come to experiencing their bodies as sexual and enjoyable. (3) The
reality of treatment demands, which are not always adequately processed before
treatment, can lead to discontinuation and even disengagement with services.
CONCLUSION: The MDT clinicians in this study emphasized the importance of
psychological input in vaginal construction. However, such input should
proactively question social norms about how women's genitalia should appear and
function. Furthermore, rather than steering patients (back) to treatment, the
entire MDT could more explicitly question social norms and help the women to do
the same. By shifting the definition of success from anatomy to personal agency,
the clinical focus is transformed from treatment to women.
PMID- 29339196
TI - Coronary Arteriovenous Fistula in Continuity With the Aortic Arch.
AB - Coronary arteriovenous fistula in continuity with the aortic arch by abnormal
vessels running along the surface of the pulmonary artery is rare. We describe 2
patients with this rare and unique arteriovenous network and discuss the issue of
diagnosis and treatment with a review of the literature.
PMID- 29339197
TI - Differential insulin and steroidogenic signaling in insulin resistant and non
insulin resistant human luteinized granulosa cells-A study in PCOS patients.
AB - Insulin resistance (IR) is one of the significant aberrations in polycystic
ovarian syndrome (PCOS), however is only observed in 70%-80% of obese PCOS and
20%-25% of lean PCOS. Hyperinsulinemia accompanies PCOS-IR along with
hyperandrogenemia against normal insulin and androgen levels in PCOS-non insulin
resistance (NIR). This could possibly be due to defects in the downstream
signaling pathways. The study thus aims to unravel insulin and steroidogenic
signaling pathways in luteinized granulosa cells isolated from PCOS-IR and NIR vs
matched controls. Luteinized granulosa cells from 30 controls and 39 PCOS were
classified for IR based on a novel method of down regulation of protein
expression of insulin receptor-beta (INSR- beta) as shown in our previous paper.
We evaluated expression of molecules involved in insulin, steroidogenic signaling
and lipid metabolism in luteinized granulosa cells followed by analysis of
estradiol, progesterone and testosterone in follicular fluid. Protein expression
of INSR- beta, pIRS (ser 307), PI(3)K, PKC-zeta, pAkt, ERK1/2, pP38MAPK and gene
expression of IGF showed differential expression in the two groups. Increased
protein expression of PPAR-gamma was accompanied by up regulation in SREBP1c,
FAS, CPT-1 and ACC-1 genes in PCOS-IR group. Expression of StAR, CYP19A1, 17 beta
HSD and 3 beta- HSD demonstrated significant decrease along with increase in
CYP11A1, FSH-R and LH-R in both the groups. Follicular fluid testosterone
increased and progesterone decreased in PCOS-IR group. This study shows how
candidate molecules that were differentially expressed, aid in designing targeted
therapy against the two phenotypes of PCOS.
PMID- 29339198
TI - CD90+ cardiac fibroblasts reduce fibrosis of acute myocardial injury in rats.
AB - OBJECTIVE: To explore the differentiation tendency of CD90+ cardiac fibroblast
(CFs) into cardiomyogenic cells in vitro and repair functions in acute myocardial
infarction rats. METHODS: CD90+ subpopulation was sorted from rat CFs by flow
cytometry. 10 MUmoL/L of 5-Azacytosine (5-aza) was used to induce differentiation
of CFs into cardiomyogenic cells. An acute myocardial infarction model was
prepared by ligation of the rat left anterior descending coronary artery. After
nuclei were labeled by DAPI, induced CD90+ CFs were injected into the infarction
marginal zone. Before coronary ligation, 40 min after ligation, and at 7 and 14
days after cell transplantation, cardiac function changes were detected by
ultrasound imaging system respectively. cTnT and endothelial cell marker VIII
factor were detected by immunofluorescence staining. Infarct size was examined by
TTC staining. Fibrosis was evaluated with masson's trichrome staining, vimentin,
type I and type III collagen staining. RESULTS: CD90+ CFs sorted by flow
cytometry was 34.9%. On day 28 after induction, the cTnT positive rate was 61.17
+/- 9.75%. Left ventricular ejection fraction (LVEF) and left ventricular
fractional shortening (LVFS) at days 7 and 14 after transplantation were
significantly increased compared with those before transplantation (P < 0.05).
LVEF and LVFS at the 14th day after transplantation were also significantly
increased compared with those at the 7th day (LVEF: 61.40 +/- 2.45% vs. 56.25 +/-
2.9%, LVFS: 33.21 +/- 0.68% vs. 30.26 +/- 2.06%, P < 0.01). Additionally, small
numbers of CD90+ CFs differentiated into cardiomyocytes and became involved in
neovascularization. CD90+ CFs and CFs reduced myocardial infarct size at days 14.
It was significantly smaller in rats with CFs transplantation group than those in
MI group(24.78 +/- 2.28% vs. 31.28 +/- 2.83%, P < 0.05), and it was also
significantly smaller in rats with CD90+CFs transplantation group than those in
CFs transplantation group (17.47 +/- 4.15% vs. 24.78 +/- 2.28%, P < 0.05).
Meanwhile, The percentage of fibrotic area and vimentin, type I and type III
collagen in the infarct border zone and infarct area were both significantly
reduced in CD90 + CFs. CONCLUSION: CD90+ CFs is the preponderant subpopulation of
cardiomyogenic differentiation, with potential use as seed cells in basic and
clinical research of heart regeneration and repair.
PMID- 29339199
TI - Neutralization of TNFR-1 and TNFR-2 modulates S. aureus induced septic arthritis
by regulating the levels of pro inflammatory and anti inflammatory cytokines
during the progression of the disease.
AB - Staphylococcal septic arthritis remains a serious medical concern due to rapid
and sustained production of inflammatory cytokines that leads to progressive and
irreversible joint destruction with high mortality rate in patients despite
adequate antibiotics treatment. TNF-alpha signalling via TNFR-1 contributes to
arthritic destruction by aggravating inflammation. Impact of TNFR-2 signalling is
not well established in this aspect. Hence the objective of our study was to
evaluate the role of dual neutralization TNFR-1 and TNFR-2 in the pathogenesis of
S. aureus infection induced septic arthritis. Mice were infected with live S.
aureus (5 * 106 cells/ml) followed by administration of TNFR-1and TNFR-2
neutralizing antibody. To measure arthritis index and osteoclastogenesis,
histology result in joint tissue and TRAP staining images of arthritis joints
have been performed respectively. Maximum reduction in the joint and paw swelling
was observed in infected mice treated with both TNFR-1 and TNFR-2 antibody. NF
kappaB signalling was found to be mainly regulated by TNFR-1 whereas TNFR-2
significantly modulated JNK pathway. Lowest levels of inflammatory cytokines like
TNF-alpha, IL-1beta, IL-6, and IFN-gamma were observed in both serum and synovial
tissues signifying maximum protection in S. aureus arthritis during combination
treatment. However IFN-gamma and IL-10 levels were significantly altered by TNFR
2 neutralization that indicates both pro and anti inflammatory role of TNFR-2
respectively. Highest decrement in ROS concentration, iNOS expression with least
MPO and lysozyme activity was detected in case of combined neutralization. During
the early phase of infection all the aforesaid inflammatory parameters remained
elevated due to lack of IL-10 as a result of TNFR-2 neutralization as IL-10
negatively modulates pro inflammatory cytokines. Increase in inflammatory
cytokines during early phase might also be responsible for decreased bacterial
count in TNFR-2 neutralized groups. Thus it can be suggested that combined
administration of TNFR-1 and TNFR-2 antibody has a beneficial effect against the
severity of S. aureus induced arthritis.
PMID- 29339200
TI - Preventing healthcare-associated Gram-negative bloodstream infections.
PMID- 29339201
TI - Laminar airflow system use across the operating surface for airborne infection
prevention in office-based surgical procedures.
PMID- 29339202
TI - An in-situ pilot study to investigate the native clinical resistance of enamel to
erosion.
AB - OBJECTIVES: To investigate the differences in susceptibility of the surface of
native and polished enamel to dietary erosion using an in-situ model. METHODS:
Thirty healthy volunteers (n = 10 per group) wore mandibular appliances
containing 2 native and 2 polished enamel samples for 30 min after which, the
samples were exposed to either an ex-vivo or in-vivo immersion in orange juice
for 5, 10 or 15 min and the cycle repeated twice with an hour's interval between
them. Samples were scanned with a non-contacting laser profilometer and surface
roughness was extracted from the data, together with step height and
microhardness change on the polished enamel samples. RESULTS: All volunteers
completed the study. For native enamel there were no statistical difference
between baseline roughness values versus post erosion. Polished enamel
significantly increased mean (SD) Sa roughness from baseline for each group
resulting in roughness change of 0.04 (0.03), 0.06 (0.04), 0.04 (0.03), 0.06
(0.03), 0.08 (0.05) and 0.09 (0.05) MUm respectively. With statistical
differences between roughness change 45 min in-vivo versus 45 min ex-vivo (p <
0.05). Microhardness significantly decreased for each polished group, with
statistical differences in hardness change between 30 min in-vivo versus 30 min
ex-vivo (p < 0.05), 45 min in-vivo versus 30 min ex-vivo (p < 0.01), 45 min in
vivo versus 45 min ex-vivo (p < 0.01). CONCLUSIONS: The native resistance to
erosion provided clinically is a combination of the ultrastructure of outer
enamel, protection from the salivary pellicle and the overall effects of the oral
environment. CLINICALTRIALS. GOV IDENTIFIER: NCT03178968. CLINICAL SIGNIFICANCE:
This study demonstrates that outer enamel is innately more resistant to erosion
which is clinically relevant as once there has been structural breakdown at this
level the effects of erosive wear will be accelerated.
PMID- 29339203
TI - Clinical performance of full rehabilitations with direct composite in severe
tooth wear patients: 3.5 Years results.
AB - OBJECTIVES: To evaluate the mid-term clinical performance of direct composite
restorations placed in patients with pathological tooth wear needing full
rehabilitation with an increase of vertical dimension of occlusion. METHODS: In a
prospective trial 34 patients (34.0 +/- 8.4 years; 25 males, 9 females) were
treated with a minimal invasive additive technique using composite restorations.
The restorative treatment protocol was to provide all teeth with composite build
up restorations in an increased vertical dimension of occlusion (VDO) using the
DSO-technique. Recall appointments were planned after 1 month, 1 and 3 years
after treatment. Restorations were scored for clinically acceptability (FDI
criteria) and scores 4 and 5 were recorded as clinically unacceptable.
Frequencies of failures and Kaplan Meier survival curves are presented and effect
of relevant variables was calculated with a multifactorial Cox regression (p <
0.05). RESULTS: 1256 Restorations were placed, 687 anterior, 324 premolar, and
245 molar restorations. After a mean observation time of 39.7 months a total of
69 failures were observed, of which 61 restorations were repaired (score 4) and 8
were replaced (score 5). Most common reasons for failure were (chip) fractures (n
= 43) and caries (n = 11). Placement of anterior restorations in two sessions led
to significant 4.6 times more failures then placed in one session. CONCLUSIONS:
In patients with severe tooth wear a full rehabilitation, in an increased
vertical dimension of occlusion, direct composite resin restorations show a 94.8%
success and 99.3% survival rate after a period of 3.5 years.
PMID- 29339204
TI - WITHDRAWN: Serum uric acid and prevalence of age-related hearing loss in the
Japanese population: Baseline data from the Aidai Cohort Study in Yawatahama.
AB - This article has been withdrawn at the request of the author(s) and/or editor.
The Publisher apologizes for any inconvenience this may cause. The full Elsevier
Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our
business/policies/article-withdrawal.
PMID- 29339205
TI - Agreement of Musculoskeletal Ultrasound and Clinical Assessment of Shoulder
Impairment in Manual Wheelchair Users With Various Duration of Spinal Cord
Injury.
AB - OBJECTIVES: To determine (1) agreement of musculoskeletal ultrasound (MSK-US)
findings of shoulder pathology and related shoulder special test results in
individuals with varied durations of manual wheelchair (MWC) use after spinal
cord injury (SCI); and (2) whether shoulder musculoskeletal impairments, per MSK
US and clinical examination, differed in individuals with SCI and varying
durations of MWC use. DESIGN: Cross-sectional cohort study. SETTING: Laboratory
setting. PARTICIPANTS: Adult volunteers (N=23) with SCI who used an MWC for
community mobility. Individuals were stratified into 3 groups based on duration
of MWC use: <5 years, 5 to 15 years, and >15 years. INTERVENTIONS: Not
applicable. MAIN OUTCOME MEASURES: Special tests for shoulder impingement and
bicipital tendonitis were performed. Bilateral shoulder MSK-US was performed,
with the Ultrasound Shoulder Pathology Rating Scale (USPRS) quantifying biceps
tendon, supraspinatus tendon, and greater tuberosity cortical surface
impairments. RESULTS: No agreement was found between MSK-US and related special
tests. Special tests failed to identify impairment in 33.3% to 100% of those
identified on MSK-US. The total USPRS score was highest in those with >15 years'
MWC use. A higher proportion of dynamic impingement (supraspinatus and biceps)
was found in those with >15 years' MWC use, with other MSK-US items having
moderate effect sizes among duration-use groups. CONCLUSIONS: MSK-US identified
shoulder impairments more frequently than commonly used special tests. A
significant increase in the presence of MSK-US shoulder impairments was
identified in the longest-duration group. This was not the case for special tests
or pain. MSK-US is an easily administered, low-cost, noninvasive method for
determining shoulder impairments and should be used in routine screening of
individuals who use an MWC after SCI.
PMID- 29339206
TI - Objective Sleep Measures in Inpatients With Subacute Stroke Associated With
Levels and Improvements in Activities of Daily Living.
AB - OBJECTIVE: To investigate whether objective polysomnographic measures of
prevalent sleep problems such as sleep-disordered-breathing (SDB) and insomnia
are associated with activities of daily living levels in inpatients at
rehabilitation units. DESIGN: Retrospective and observational study. SETTING:
Single rehabilitation center. PARTICIPANTS: Inpatients with subacute stroke
(N=123) (61.6+/-13.1 years; 23.8+/-3.4 kg/m2; 33% women; 90.5+/-36.7 days post
stroke) underwent a 1-night polysomnographic study and a 1-month inpatient
rehabilitation program. MAIN OUTCOME MEASURES: Admission and discharge Barthel
Index (BI) scores and its change scores. RESULTS: One hundred three (92%)
patients had moderate-to-severe SDB (46.7+/-25.1 events/h in the apnea-hypopnea
index), and 24 (19.5%) patients had acceptable continuous positive airway
pressure adherence. Diverse values were found for total sleep time (259+/-71
min), sleep efficiency (69.5%+/-19.3%), sleep latency (24.3+/-30.9 min), and
wakefulness after sleep onset (93.1+/-74.2 min). Admission BI scores and the BI
change scores were 33.8+/-23.2 and 10.1+/-9.2, respectively. The National
Institutes of Health Stroke Scale (NIHSS, 10.2+/-5.6), available in 57 (46%)
patients, was negatively associated with admission levels and gains in BI change
scores (P<.001, =0.002, respectively) in a univariate analysis. In regression
models with backward selection, excluding NIHSS score, both age (P=.025) and
wakefulness after sleep onset (P<.001) were negatively associated (adjusted
R2=0.260) with admission BI scores. Comorbidity of hypertension; sleep latency
percentage of stage 1, non-rapid eye movement sleep; and desaturation events >=4%
(P<.001, 0.001, 0.021, and 0.043, respectively; adjusted R2=0.252) were
negatively associated with BI score gains. CONCLUSIONS: Based on objective sleep
measures, insomnia rather than SDB in inpatients with subacute stroke was
associated negatively with admission levels of activity of daily living and its
improvement after a 1-month rehabilitation course.
PMID- 29339207
TI - Nicaraven reduces cancer metastasis to irradiated lungs by decreasing CCL8 and
macrophage recruitment.
AB - Radiotherapy for cancer patients damages normal tissues, thereby inducing an
inflammatory response and promoting cancer metastasis. We investigated whether
nicaraven, a compound with radioprotective and anti-inflammatory properties,
could attenuate radiation-induced cancer metastasis to the lungs of mice.
Nicaraven and amifostine, another commercial radioprotective agent, had limited
effects on both the radiosensitivity of Lewis lung carcinoma cells in vitro and
radiation-induced tumor growth inhibition in vivo. Using experimental and
spontaneous metastasis models, we confirmed that thorax irradiation with 5 Gy X
rays dramatically increased the number of tumors in the lungs. Interestingly, the
number of tumors in the lungs was significantly reduced by administering
nicaraven but not by administering amifostine daily after radiation exposure.
Furthermore, nicaraven administration effectively inhibited CCL8 expression and
macrophage recruitment in the lungs 1 day after thorax irradiation. Our data
suggest that nicaraven attenuates radiation-induced lung metastasis, likely by
regulating the inflammatory response after radiation exposure.
PMID- 29339208
TI - Targeted shRNA-loaded liposome complex combined with focused ultrasound for blood
brain barrier disruption and suppressing glioma growth.
AB - Our previous studies have demonstrated that focused ultrasound (FUS) combined
with DNA-loaded microbubbles (MBs) can induce noninvasive, reversible, local
disruption of the blood brain barrier (BBB) and enable targeted exogenous gene
transfer into the central nervous system. However, due to low gene loading or the
absence of positive targeting, to date, there has been no therapeutic effect of
MBs combined with FUS in tumor treatment. In the current study, we adopted a
phospholipid complex that exhibited sufficient gene loading and peptide-mediated
targeting to delay glioma growth. First, we bound MBs to shBirc5-lipo-NGR, which
performed the dual function of tumor cell targeting and effective gene loading.
Next, we demonstrated that FUS-aided MB-shBirc5-lipo-NGR exhibited a higher
transfection efficiency compared with the control group. Finally, we evaluated
the silencing effect of shBirc5 using an apoptosis assay, real time-polymerase
chain reaction (PCR), western blotting (WB) in vitro and a volume measurement
survival analysis in vivo. The experimental group exhibited a significant
therapeutic effect, while the FUS-only, MB-shBirc5-lipo-NGR-only and FUS-aided MB
shControl-lipo-NGR groups displayed no changes in tumor growth or survival time
(P < .01). Consequently, our study indicated that MB-shBirc5-lipo-NGR combined
with FUS is a promising new RNA interference technique for the treatment of
glioma.
PMID- 29339209
TI - Extratumoral PD-1 blockade does not perpetuate obesity-associated inflammation in
esophageal adenocarcinoma.
AB - Checkpoint inhibitors, such as anti-PD-1 (Programmed death-1), are transforming
cancer treatment for inoperable or advanced disease. As the incidence of obesity
associated malignancies, including esophageal adenocarcinoma (EAC) continues to
increase and treatment with checkpoint inhibitors are being FDA approved for a
broader range of cancers, it is important to assess how anti-PD-1 treatment might
exacerbate pre-existing inflammatory processes at other sites. Outside the EAC
tumor, the omentum and liver were found to be enriched with substantial
populations of PD-1 expressing T cells. Treatment of omental and hepatic T cells
with anti-PD-1 (clone EH12.2H7) did not enhance inflammatory cytokine expression
or proliferation, but transiently increased CD107a expression by CD8+ T cells.
Importantly, PD-1-expressing T cells are significantly lower in EAC tumor post
neoadjuvant chemoradiotherapy, suggesting that combination with specific
conventional treatments may severely impair the efficacy of anti-PD-1
immunotherapy. This study provides evidence that systemically administered anti
PD-1 treatment is unlikely to exacerbate pre-existing T cell-mediated
inflammation outside the tumor in obesity-associated cancers, such as EAC.
Furthermore, our data suggests that studies are required to identify the negative
impact of concomitant therapies on PD-1 expression in order to boost overall
response rates.
PMID- 29339210
TI - The NLRP3 inflammasome: Role in metabolic disorders and regulation by metabolic
pathways.
AB - Inflammasomes are large multimolecular complexes present in the cytosol of
stimulated immune cells; they mediate the activation of caspase-1, leading to
cellular pyroptosis. So far, a variety of studies on inflammasomes have emerged,
and the best-studied is the NLRP3 inflammasome that is involved in many
inflammatory responses. Furthermore, its relationship with metabolism is gaining
increasing attention in this field. In this review, we discuss the importance of
the NLRP3 inflammasome in metabolic disorders and its close association with
metabolic pathways.
PMID- 29339211
TI - Long non-coding RNA XIST promotes TGF-beta-induced epithelial-mesenchymal
transition by regulating miR-367/141-ZEB2 axis in non-small-cell lung cancer.
AB - Growing evidence shows that lncRNA XIST functions as an oncogene accelerating
tumor progression. Transforming growth factor beta (TGF-beta)-induced epithelial
mesenchymal transition (EMT) plays a key role in tumor metastasis. However, it is
still unclear whether lncRNA XIST is implicated in TGF-beta-induced EMT and
influences cell invasion and metastasis in non-small-cell lung cancer (NSCLC).
Here, we observed increased expression of lncRNA XIST and ZEB2 mRNA in metastatic
NSCLC tissues. Knockdown of lncRNA XIST inhibited ZEB2 expression, and repressed
TGF-beta-induced EMT and NSCLC cell migration and invasion. Being in consistent
with the in vitro findings, the in vivo experiment of metastasis showed that
knockdown of lncRNA XIST inhibited pulmonary metastasis of NSCLC cells in mice.
In addition, knockdown of ZEB2 expression can inhibit TGF-beta-induced EMT and
NSCLC cell migration and invasion. Mechanistically, lncRNA XIST and ZEB2 were
targets of miR-367 and miR-141. Furthermore, both miR-367 and miR-141 expression
can be upregulated by knockdown of lncRNA XIST. Taken together, our study reveals
that lncRNA XIST can promote TGF-beta-induced EMT and cell invasion and
metastasis by regulating miR-367/miR-141-ZEB2 axis in NSCLC.
PMID- 29339213
TI - NRP-2 in tumor lymphangiogenesis and lymphatic metastasis.
AB - Neuropilin-2 (NRP-2) not only functions as a receptor for semaphorins, a family
of neural axon guidance factors, but also interacts with VEGFs, a family of
vascular endothelial growth factors. As an independent receptor or a co-receptor,
NRP-2 binds to ligands VEGF-C/D, activates the VEGF-C/D-NRP-2 signaling axis, and
further regulates lymphangiogenesis-associated factors in both lymphatic
endothelial cells (LECs) and some tumor cells during tumor progression. Via VEGF
C/D-NRP-2 axis, NRP-2 induces LEC proliferation, reconstruction and
lymphangiogenesis and subsequently promotes tumor cell migration, invasion and
lymphatic metastasis. There are similarities and differences among NRP-1, NRP-2
and VEGFR-3 in chemical structure, ligand specificity, chromosomal location,
soluble protein forms, cellular functions and expression profiles. High
expression of NRP-2 in LECs and tumor cells has been observed in different
anatomic sites, histological patterns and progression stages of various tumors,
especially during tumor lymphangiogenesis and lymphatic metastasis, and therefore
the NRP-2 and VEGF-C/D-NRP-2 axis are closely related to tumor development,
progression, invasion, and metastasis. In addition, it is important for prognosis
of tumor. The studies on NRP-2 targeted therapy have recently achieved some
successes, utilizing NRP-2 blocking antibodies, NRP-2 inhibitory peptides,
soluble NRP-2 antagonists, small molecule inhibitors and various NRP-2 gene
therapeutic strategies.
PMID- 29339212
TI - Autophagy and T cell metabolism.
AB - Autophagy, a highly conserved catabolic process that involves the degradation and
recycling of intracellular components in the lysosome, has emerged as a key
process in the maintenance of T cell homeostasis and the regulation of T cell
differentiation and function. In this review, we provide an overview of the
mechanisms that mediate the regulation of autophagy in T cells and discuss
different cellular processes that are under the control of autophagy in CD4+ and
CD8+ T cells. A special emphasis is placed on the role that autophagy plays in
the modulation of T cell metabolism and the consequences of this regulation on
functional states and programs of differentiation in specific T cell populations.
PMID- 29339214
TI - Preparation and spectral properties of europium hydrogen squarate microcrystals.
AB - A simple scheme for preparation of europium hydrogen squarate octahydrate
microcrystals, Eu(HSq)3.8H2O is demonstrated. The microcrystalline powders
obtained have a potential application as non-centrosymmetric and UV radiation -
protective hybrid optical material. The site-symmetry of the Eu - ion is C2V or
lower, obtained from diffuse reflectance spectra. The formation of europium
hydrogen squarate is supported by IR - spectroscopy, UV-vis spectroscopy,
chemical analysis and X-ray diffraction. A detailed analysis of the UV-vis and IR
spectra of the micropowders prepared is presented.
PMID- 29339215
TI - Registration in the international prospective register of systematic reviews
(PROSPERO) of systematic review protocols was associated with increased review
quality.
AB - OBJECTIVES: A priori registration of systematic review protocols in international
prospective register of systematic reviews (PROSPERO) can help reduce selective
reporting of outcomes. The aim of this study was to assess the association
between registration of orthodontic systematic reviews in PROSPERO and review
quality with the Assessment of Multiple Systematic Reviews (AMSTAR) tool. STUDY
DESIGN AND SETTING: Seven databases were searched for systematic reviews
with/without meta-analysis in orthodontics published between 2012 and 2016. After
duplicate study selection and data extraction, the quality of identified reviews
was assessed in duplicate with the AMSTAR tool. Descriptive statistics of medians
and interquartile ranges (IQRs) and chi-square/Fisher exact tests were
calculated. Univariable/multivariable linear regression modeling was implemented
to assess the effect of review registration on %AMSTAR score at alpha of 5%.
RESULTS: A total of 182 orthodontic systematic reviews were identified, 37
(20.3%) of which were registered. Considerable differences were seen in AMSTAR
between registered (median = 86.4%; IQR = 77.3-95.5%) and nonregistered reviews
(median = 72.7%; IQR = 59.1-81.8%). After adjustment, registration in PROSPERO
was associated with an average increase in %AMSTAR score of 6.6% (95% confidence
interval = 1.0-12.3%). CONCLUSION: Although only a small percentage of
orthodontic systematic reviews was registered a priori in PROSPERO, registered
reviews were of higher quality than nonregistered reviews.
PMID- 29339216
TI - In vivo biotinylated calpastatin improves the affinity purification of human m
calpain.
AB - Recently we established a novel affinity purification method for calpain by
exploiting the specific and reversible binding properties of its intrinsically
disordered protein inhibitor, calpastatin. The immobilization strategy relied on
the strength and specificity of the biotin - streptavidin interaction. Here, we
report an improved and optimized method that even enables the general
applicability of in vivo biotinylated (intrinsically disordered) proteins in any
affinity capture strategy. Since in vitro chemical biotinylation is only
accomplished with reagents that lack exact site specificity, it can not only
cause sample heterogeneity but it can also hamper the functionality of the
biotinylated molecules. Therefore, we have developed a recombinant expression
protocol to produce in vivo biotinylated human calpastatin domain 1 (hCSD1) in
Escherichia coli. We have experimentally verified that the biotinylated
polypeptide tag is compatible with the intrinsically disordered state of hCSD1
and that it does not influence the functional properties of this intrinsically
disordered protein (IDP). The in vivo biotinylated hCSD1 was then used without
the need of any prepurification step prior to the affinity capturing of its
substrate, human m-calpain. This leads to a simplified purification strategy that
allows capturing the calpain efficiently from a complex biological mixture with
only a single chromatogaphic step and in a considerably reduced timeframe. Our
approach is generally applicable through the in vivo biotinylation of any IDP of
interest, and its practical implementation will showcase the power to exploit the
properties of IDPs in affinity capture strategies.
PMID- 29339217
TI - Effects of rutin on the physicochemical properties of skin fibroblasts membrane
disruption following UV radiation.
AB - Human skin provides the body's first line of defense against physical and
environmental assaults. This study sought to determine how rutin affects the
membrane electrical properties, sialic acid content, and lipid peroxidation
levels of fibroblast membranes after disruption by ultraviolet (UV) radiation.
Changes in cell function may affect the basal electrical surface properties of
cell membranes, and changes can be detected by electrokinetic measurements. The
charge density of the fibroblast membrane surface was measured as a function of
pH. A four-component equilibrium model was used to describe the interaction
between ions in solution and ions on the membrane surface. Agreement was found
between experimental and theoretical charge variation curves of fibroblast cells
between pH 2.5 and 8. Sialic acid content was determined by Svennerholm's
resorcinol method, and lipid peroxidation was estimated by measuring the
malondialdehyde level. Compared to untreated cells, ultraviolet A (UVA)- or
ultraviolet B (UVB)-treated skin cell membranes exhibited higher concentrations
of acidic functional groups and higher average association constants with
hydroxyl ions, but lower average association constants with hydrogen ions.
Moreover, our results showed that UVA and UVB radiation is associated with
increased levels of sialic acid and lipid peroxidation products in fibroblasts.
Rutin protected cells from some deleterious UV-associated membrane changes,
including changes in electrical properties, oxidative state, and biological
functions.
PMID- 29339218
TI - Prophylactic efficacy of patchoulene epoxide against ethanol-induced gastric
ulcer in rats: Influence on oxidative stress, inflammation and apoptosis.
AB - Patchoulene epoxide (PAO), a tricyclic sesquiterpene isolated from the long
stored patchouli oil, has been demonstrated the anti-inflammatory activity in
vivo based on our previous study. However, the gastric protective effect of PAO
still remains unknown. Therefore, in the present study, ethanol-induced gastric
ulcer model was carried out to evaluate the anti-ulcerogenic activity of PAO and
to elucidate the potential mechanisms that involves. According to our results,
macroscopic examination revealed that PAO could significantly reduce ethanol
induced gastric ulcer areas as compared with the vehicle group, which was also
supported by the histological evaluation result. As for its potential mechanism,
the anti-inflammatory activity of PAO contributed to gastric protection through
reversing the imbalance between pro- and anti-inflammatory cytokines and
modulating the expressions of NF-kappaB pathway-related proteins including p
IkappaBalpha, IkappaBalpha, p-p65 and p65. Besides, PAO was able to enhance the
expressions of antioxidant enzymes including glutathione (GSH), superoxide
dismutase (SOD) and catalase (CAT), and down-regulate malonaldehyde (MDA), an
indicator of lipid peroxidation. Furthermore, immunohistochemistry analysis
exhibited potent anti-apoptosis effect of PAO, as evidence by down-regulating the
protein expression of caspase-3, Fas and Fasl. Additionally, we also demonstrated
that PAO could replenish PGE2 and NO mucosal defense. In conclusion, these
findings suggested that PAO has gastric protective activity against ethanol and
this might be related to its influence on inflammatory response, oxidative
stress, apoptosis cascade and gastric mucosal defense.
PMID- 29339219
TI - Caffeine-supplemented diet modulates oxidative stress markers and improves
locomotor behavior in the lobster cockroach Nauphoeta cinerea.
AB - The effects of caffeine supplementation is well documented in conventional animal
models, however, in the lobster cockroaches Nauphoeta cinerea, they have not been
reported. Thus, the aim of this study was to investigate the locomotor behavior
and biochemical endpoints in the head of the nymphs of N. cinerea following 60
days exposure to food supplemented with 0, 0.5, 1.0, 2.5, 5.0 and 10.0 mg of
caffeine/g of diet. The analysis of the locomotor behavior using the video
tracking software, Any-maze, for 12 min revealed that caffeine supplementation
caused significant behavioral improvement. There was increase in distance
travelled, velocity, frequency of rotation and turn angle (stereotypical behavior
such as circling movements), and this was supported by the representative track
plots of the path travelled by cockroaches in the open-field arena. In addition,
caffeine supplementation markedly increased total thiol and non-protein thiol
glutathione (GSH) levels in the heads of cockroaches, and this was in parallel
with significant reduction of lipid peroxidation and free Fe(II) content. Taking
together, our results indicate that long-term caffeine supplementation may exert
preventive effects against oxidative stress and support the use of N. cinerea as
an efficient alternative model to assess the efficacy of food molecules.
PMID- 29339220
TI - A new chimeric triple reporter fusion protein as a tool for in vitro and in vivo
multimodal imaging to monitor the development of African trypanosomes and
Leishmania parasites.
AB - Trypanosomiases and leishmaniases, caused by a group of related protist
parasites, are Neglected Tropical Diseases currently threatening >500 million
people worldwide. Reporter proteins have revolutionised the research on
infectious diseases and have opened up new advances in the understanding of
trypanosomatid-borne diseases in terms of both biology, pathogenesis and drug
development. Here, we describe the generation and some applications of a new
chimeric triple reporter fusion protein combining the red-shifted firefly
luciferase PpyREH9 and the tdTomato red fluorescent protein, fused by the TY1
tag. Expressed in both Trypanosoma brucei brucei and Leishmania major transgenic
parasites, this construct was successfully assessed on different state-of-the-art
imaging technologies, at different scales ranging from whole organism to cellular
level, both in vitro and in vivo in murine models. For T. b. brucei, the
usefulness of this triple marker to monitor the entire parasite cycle in both
tsetse flies and mice was further demonstrated. This stable reporter allows to
qualitatively and quantitatively scrutinize in real-time several crucial aspects
of the parasite's development, including the development of African trypanosomes
in the dermis of the mammalian host. We briefly discuss developments in bio
imaging technologies and highlight how we could improve our understanding of
parasitism by combining the genetic engineering of parasites to the one of the
hosting organisms in which they complete their developmental program.
PMID- 29339221
TI - The Founding Fathers vs Jerome Cochran: Organization and Development of the
Southern Surgical and Gynecological Association in Birmingham.
PMID- 29339222
TI - Measurement variability of liver metastases from neuroendocrine tumors on
different magnetic resonance imaging sequences.
AB - PURPOSE: To assess dimension measurement variability of liver metastases from
neuroendocrine tumors (LMNET) on different magnetic resonance imaging (MRI)
sequences. MATERIAL AND METHODS: In this institutional review board-approved
retrospective study from January 2011 to December 2012, all liver MRI
examinations performed at our department in patients with at least one measurable
LMNET according to response evaluation criteria in solid tumors (RECIST1.1) were
included. Up to two lesions were selected on T2-weighted MR images. Three
reviewers independently measured long axes of 135 hepatic metastases in 30
patients (16 men, 14 women, mean age 61+/-11.4 (SD) years; range 28-78 years),
during two separate reading sessions, on T2-weighted, diffusion-weighted MRI
(DWI) (b; 50, 400, 800 s/mm2) and arterial, portal and late phases after
intravenous administration of a gadolinium chelate. Intraclass-correlation
coefficients and Bland-Altman plots were used to assess intra-and interobserver
variability. RESULTS: Intra- and interobserver agreements ranged between 0.87
0.98, and 0.88-0.97, respectively. Intersequence agreements ranged between 0.92
[95%CI: 0.82-0.98] and 0.98 [95%CI: 0.93-0.99]. 95% limits of agreement for
measurements were -10.2%,+8.9% for DWI (b=50s/mm2) versus -21.9%,+24.2% and
15.8,+17.2% for arterial and portal phases, respectively. CONCLUSION: An
increase<9% in measurement and a decrease of -10% on DWI should not be considered
as true changes, with 95% confidence, versus 24% and -22% on arterial and 17%,
16% on portal phases, respectively. DWI might thus be the most reliable MR
sequence for monitoring size variations of LMNETs.
PMID- 29339223
TI - Leishmania infections in Austrian soldiers returning from military missions
abroad: a cross-sectional study.
AB - OBJECTIVES: The incidence of leishmaniasis is known to increase in conflict
areas. The aims of this study were to determine the exposure to Leishmania
species in Austrian soldiers returning from missions abroad and to assess
possible risk factors. METHODS: A retrospective explorative cross-sectional
serologic study was conducted in 225 healthy Austrian soldiers returning from UN
or EU peacekeeping missions in Syria, Lebanon and Bosnia and Herzegovina (BIH).
Sera were tested for anti-Leishmania antibodies using a commercial enzyme-linked
immunosorbent assay. All positive individuals were screened for Leishmania DNA by
PCR targeting the ITS1 region using EDTA blood samples. RESULTS: In total, 13.3%
(30/225) of the individuals tested were either positive (8%, 18/225) or
borderline (5.3%, 12/225) in the enzyme-linked immunosorbent assay, with the
highest seroprevalence in soldiers returning from Syria (17.8%, 18/101; 12
positive, six borderline), second from Lebanon (11.1%, 7/63; four positive, three
borderline) and lowest from BIH (8.2%, 5/61; two positive, three borderline). Ten
soldiers returning from Syria and one from BIH were also positive for Leishmania
DNA. Six of these were identified as Leishmania donovani/infantum complex, two as
L. tropica and another three as mixed infections by DNA sequencing. Epidemiologic
data were collected via a questionnaire, and seropositivity was correlated with a
history of insect bites that took a long time to heal (odds ratio, 5.33; 95%
confidence interval, 1.23-23.04; p 0.025). CONCLUSIONS: Although pretravel
serologic data were not available in this study, the exposure of soldiers to
Leishmania spp. during their missions can be assumed to be considerable. Because
even asymptomatic infections may resurge in case of emerging immunodeficiencies,
adequate prevention measures seem important.
PMID- 29339224
TI - Emerging souvenirs-clinical presentation of the returning traveller with imported
arbovirus infections in Europe.
AB - BACKGROUND: Arboviruses are an emerging group of viruses that are causing
increasing health concerns globally, including in Europe. Clinical presentation
usually consists of a nonspecific febrile illness that may be accompanied by
rash, arthralgia and arthritis, with or without neurological or haemorrhagic
syndromes. The range of differential diagnoses of other infectious and
noninfectious aetiologies is broad, presenting a challenge for physicians. While
knowledge of the geographical distribution of pathogens and the current
epidemiological situation, incubation periods, exposure risk factors and
vaccination history can help guide the diagnostic approach, the nonspecific and
variable clinical presentation can delay final diagnosis. AIMS AND SOURCES: This
narrative review aims to summarize the main clinical and laboratory-based
findings of the three most common imported arboviruses in Europe. Evidence is
extracted from published literature and clinical expertise of European arbovirus
experts. CONTENT: We present three cases that highlight similarities and
differences between some of the most common travel-related arboviruses imported
to Europe. These include a patient with chikungunya virus infection presenting in
Greece, a case of dengue fever in Turkey and a travel-related case of Zika virus
infection in Romania. IMPLICATIONS: Early diagnosis of travel-imported cases is
important to reduce the risk of localized outbreaks of tropical arboviruses such
as dengue and chikungunya and the risk of local transmission from body fluids or
vertical transmission. Given the global relevance of arboviruses and the
continuous risk of (re)emerging arbovirus events, clinicians should be aware of
the clinical syndromes of arbovirus fevers and the potential pitfalls in
diagnosis.
PMID- 29339225
TI - Metabolism and pharmacokinetics of a potent N-acylindole antagonist of the OXE
receptor for the eosinophil chemoattractant 5-oxo-6,8,11,14-eicosatetraenoic acid
(5-oxo-ETE) in rats and monkeys.
AB - We previously identified the indole 264 as a potent in vitro antagonist of the
human OXE receptor that mediates the actions of the powerful eosinophil
chemoattractant 5-oxo-ETE. No antagonists of this receptor are currently
commercially available or are being tested in clinical studies. The lack of a
rodent ortholog of the OXE receptor has hampered progress in this area because of
the unavailability of commonly used mouse or rat animal models. In the present
study, we examined the feasibility of using the cynomolgus monkey as an animal
model to investigate the efficacy of orally administered 264 in future in vivo
studies. We first confirmed that 264 is active in monkeys by showing that it is a
potent inhibitor of 5-oxo-ETE-induced actin polymerization and chemotaxis in
granulocytes. The major microsomal metabolites of 264 were identified by
cochromatography with authentic chemically synthesized standards and LC-MS/MS as
its omega2-hydroxy and omega2-oxo derivatives, formed by omega2-oxidation of its
hexyl side chain. Small amounts of omega1-oxidation products were also
identified. None of these metabolites have substantial antagonist potency. High
levels of 264 appeared rapidly in the blood following oral administration to both
rats and monkeys, and declined to low levels by 24 h. As with microsomes, its
major plasma metabolites in monkeys were omega2-oxidation products. We conclude
that the monkey is a suitable animal model to investigate potential therapeutic
effects of 264. This, or a related compound with diminished susceptibility to
omega2-oxidation, could be a useful therapeutic agent in eosinophilic disorders
such as asthma.
PMID- 29339226
TI - Model and methods to assess hepatic function from indocyanine green fluorescence
dynamical measurements of liver tissue.
AB - The indocyanine green (ICG) clearance, presented as plasma disappearance rate is,
presently, a reliable method to estimate the hepatic "function". However, this
technique is not instantaneously available and thus cannot been used intra
operatively (during liver surgery). Near-infrared spectroscopy enables to assess
hepatic ICG concentration over time in the liver tissue. This article proposes to
extract more information from the liver intensity dynamics by interpreting it
through a dedicated pharmacokinetics model. In order to account for the different
exchanges between the liver tissues, the proposed model includes three
compartments for the liver model (sinusoids, hepatocytes and bile canaliculi).
The model output dependency to parameters is studied with sensitivity analysis
and solving an inverse problem on synthetic data. The estimation of model
parameters is then performed with in-vivo measurements in rabbits (El-Desoky et
al. 1999). Parameters for different liver states are estimated, and their link
with liver function is investigated. A non-linear (Michaelis-Menten type)
excretion rate from the hepatocytes to the bile canaliculi was necessary to
reproduce the measurements for different liver conditions. In case of bile duct
ligation, the model suggests that this rate is reduced, and that the ICG is
stored in the hepatocytes. Moreover, the level of ICG remains high in the blood
following the ligation of the bile duct. The percentage of retention of
indocyanine green in blood, which is a common test for hepatic function
estimation, is also investigated with the model. The impact of bile duct ligation
and reduced liver inflow on the percentage of ICG retention in blood is studied.
The estimation of the pharmacokinetics model parameters may lead to an evaluation
of different liver functions.
PMID- 29339227
TI - A novel biphenolic ligand for selective Mg2+ and Zn2+ ions sensing followed by
colorimetric, spectroscopic and cell imaging methods.
AB - The (E)-2-((2-hydrohy-5-methylphenylimino) methyl) phenol ligand was synthesized.
The receptor was characterized by IR, 1H and 13C NMR and CHN analysis. The ligand
exhibits colorimetric and fluorometric sensing of Zn2+ and Mg2+ ions in semi
aqueous medium (DMSO-H2O). The receptor was tested with series of transition
metal ions (Cr2+, Fe2+, Ni2+, Co2+, Cu2+, Zn2+) and heavy metal ions (Sn2+, Pd2+,
Ce2+, Hg2+, Cd2+) and the essential human body elements like Ca2+, Mg2+, Na+ and
K+ ions. The naked eye colorimetric sensing was absorbed only for Zn2+ and Mg2+.
Both ions (ZnCl2 and MgCl2 in H2O), when added to the colorless solutions of the
receptor of about 1 equivalence in incremental additions turn the solution into
bright turmeric yellow. All other ions remain inactive, in colorimetric sensing.
Further the Zn2+ and Mg2+ ions were probed by absorption and emission
spectroscopy through incremental addition of respective metal ions. The in-situ
deprotonation of the ligand on both Mg2+ and Zn2+ ions binding was confirmed by
1H NMR titration studies. The imino nitrogen of the receptor is not coordinated
to the metal ions. The Job's plot studies reveal the 1:2 binding ratio of metal
ions to the receptor. The high fold fluorescence output on metal ions binding was
positively used to sense the Zn2+ and Mg2+ ions, separately and together in HeLa
cancer cells through cell imaging.
PMID- 29339228
TI - Stability and plasmatic protein binding of novel zidovudine prodrugs: Targeting
site ii of human serum albumin.
AB - Despite its vastly demonstrated clinical efficacy, zidovudine (AZT) exhibits
several suboptimal pharmacokinetic properties. In particular, its short plasmatic
half-life (t1/2 ~ 1 h) is related to its low bound fraction to whole plasmatic
proteins and in particular to human serum albumin (HSA). The design of prodrugs
constitutes a promising strategy to enhance AZT pharmacokinetic properties,
including its affinity for HSA. Recently, we reported the synthesis and chemical
stability evaluation of three novel prodrugs of AZT obtained by derivatization
with dicarboxylic acids (1-3). In this work, we present the design, synthesis and
evaluation of chemical and enzymatic stabilities of a novel series of double
prodrugs of AZT obtained by derivatization of 1-3 with a methylated l
phenylalanine moiety (4-6). In addition, the plasmatic protein binding properties
were studied both by experimental and theoretical techniques. Prodrugs 4-6 were
found to be relatively stable at pH 7.4 (t1/2 between 4.1 and 57.8 h), while also
demonstrated adequate stabilities in human plasma at 37 degrees C (t1/2 between
1.0 and 2.1 h). Also, prodrugs 4-6 were able to regenerate AZT at a rate that
depended on the length of the alkyl chain in 1-3. Additionally, 4-6 exhibited a
significantly increased binding to plasmatic proteins (between 52.1 and 72.5%)
with respect to AZT (12%) and 1-3 (between 26 and 34%). It is noteworthy that the
displacement experiments with HSA site I and II markers, demonstrated that 4-6
bound to a different site than that of AZT and 1-3. Molecular modeling studies
(i.e. molecular docking and free energy of binding analysis) were applied to shed
light at an atomistic level on the pharmacodynamic properties driving the
interaction of 4-6 with HSA. Overall, the present work provides a state of the
art contribution to the design and development of novel prodrugs of AZT with
optimized pharmacokinetic properties.
PMID- 29339229
TI - A rare case of Candida glabrata spondylodiscitis: case report and literature
review.
AB - BACKGROUND: Spondylodiscitis is an infection of the vertebral column, the
incidence of which is increasing due to an increase in the susceptible population
and improved ascertainment. This disease has been associated with a wide range of
microorganisms. Fungal spondylodiscitis is uncommon (0.5-1.6%) and strongly
associated with immunosuppression and diabetes (Gouliouris et al., 2010). A rare
case of Candida glabrata spondylodiscitis in a non-neutropenic diabetic patient
is reported herein, along with a review of the literature. CASE REPORT: A case of
C. glabrata spondylodiscitis of L3-L4 metameres was diagnosed. The diagnosis was
obtained through open biopsy of an abscess and culture examination. The patient
was treated with anidulafungin and surgical debridement of the lesion.
CONCLUSIONS: The diagnosis of spondylodiscitis is often delayed or missed.
Physicians should consider this entity in the differential diagnosis of lumbar
pain in order to initiate an appropriate therapy to prevent spinal cord lesions
and disability. This is particularly relevant in the case of a fungal aetiology,
as there is a recognized global shift towards invasive candidiasis due to non
albicans Candida species, in particular C. glabrata, which has variable
susceptibility to antifungal drugs.
PMID- 29339230
TI - Balanced crystalloids vs 0.9% saline for adult patients undergoing non-renal
surgery: A meta-analysis.
AB - BACKGROUND: Fluid maintenance and resuscitation is an important strategy during
major surgeries. There has been a debate on the choice of crystalloids over the
past decades. 0.9% saline (normal saline) is more likely to cause hyperchloremic
acidosis when compared to balanced crystalloids with low chloride content. Meta
analyses comparing these two kinds of crystalloids have been performed in renal
transplantations. We aim to compare the safety of balanced crystalloids to normal
saline among adult patients undergoing non-renal surgery. METHODS: Relevant
articles were searched through PubMed, Embase and the Cochrane Library. Nine
randomized controlled trials (including 871 participants) comparing balanced
crystalloids to normal saline on adult patients undergoing non-renal surgery were
finally included. Possible effects were calculated using meta-analysis. RESULTS:
Patients in the normal saline group had significantly lower postoperative pH (MD:
0.05; 95% CI: 0.04-0.06; p < .001; I2 = 82%) and base excess (MD: 2.04; 95% CI:
1.44-2.65; p < .001; I2 = 87%). The postoperative serum chloride level was
significantly higher in the normal saline group (MD: -4.79; 95% CI: -8.13~-1.45;
p = .005; I2 = 95%). CONCLUSION: Comparing to normal saline, balanced
crystalloids are more beneficial in keeping postoperative electrolytes and acid
base balance among adult patients undergoing non-renal surgery. Future researches
should pay more attention to meaningful clinical outcomes concerning the safety
of balanced crystalloids and normal saline.
PMID- 29339231
TI - Respiratory patterns in field collected brown locust, Locustana pardalina, in the
gregarious phase.
AB - In this paper we report on the metabolic rates and respiratory patterns measured
from gregarious brown locusts, Locustana pardalina, collected from the Nama Karoo
region in South Africa. All five instar hopper stages and adults were collected
over a three year period when significant numbers of locust swarms were seen.
Flow-through respirometry was used to measure the CO2 emission from individual
locusts from all the developmental stages and adults within a week of collection.
Carbon dioxide emission scaled hypometrically with mass, 0.863 +/- 0.026. Except
in the 1st and 5th instar stage there was no difference in the mass specific rate
of CO2 emission (VCO2). These had significantly
higher metabolic rates compared to the other stages which reflects their biology,
with the 1st instar undergoing rapid growth and the 5th instar also undergoing
rapid growth and development in preparation for becoming an adult. The 1st
instars used a form of continuous gas exchange while all the other stages showed
discontinuous gas exchange cycles. A clear burst phase and interburst periods
could be seen. The 2nd and 3rd instars use mainly diffusion to expel CO2 and so
exhibited an open form of the burst phase. There was an increase in CO2 volleys
seen in the burst phase from the 4th instar stage onwards thus indicating an
increased use of convection. There was no change in the duration or frequency of
the discontinuous gas exchange cycles through the locust development or with body
mass.
PMID- 29339232
TI - Diapause in Drosophila melanogaster - Photoperiodicity, cold tolerance and
metabolites.
AB - Unlike many insects where photoperiod per se induces diapause, reproductive
arrest in Drosophila melanogaster adult females is observed at colder
temperatures and can be enhanced by shorter photoperiods. Traditional
experimental protocols raise flies at 25 degrees C from the larval stage and
then the adults are placed at 12 degrees C for between 12 and 28 days. After 12
days diapause levels are usually higher than at 28 days, suggesting that the
flies are in a cold induced quiescence, rather than a true diapause. By raising
flies at more realistic lower temperatures, we observe quite dramatic and counter
intuitive effects on diapause, whose levels nevertheless correlate with various
indices of cryoprotectant metabolites as well as resistance to chill shock. We
also observe that photoperiodic effects are minimised when very small temperature
oscillations associated with the light-dark incubator cycles are neutralised. Our
results suggest that the reported photoperiodic component of fly diapause, at
least in these strains, is mostly due to thermoperiodic rather than photoperiodic
stimuli. In addition, the metabolite and chill shock analyses reveal that even by
12 days, flies are entering a state that is resistant to environmental stresses.
PMID- 29339233
TI - FTIR as an easy and fast analytical approach to follow up microbial growth during
fungal pretreatment of poplar wood with Phanerochaete chrysosporium.
AB - Since the determination of the fermentation kinetics is one of the main
challenges in solid state fermentation, the quantitative measurement of biomass
growth during microbial pretreatment by FTIR spectroscopy in Attenuated Total
Reflectance mode was evaluated. Peaks at wave numbers of 1651 cm-1 and 1593 cm-1
showed to be affected during pretreatment of poplar wood particles by
Phanerochaete chrysosporium MUCL 19343. Samples with different microbial biomass
fractions were obtained from two different experiments, i.e., shake flask and
fixed-bed reactor experiments. The glucosamine concentration was compared to the
normalized absorbance ratio of the 1651 cm-1 to 1593 cm-1 peak, measured by FTIR
ATR, and resulted in a linear relationship. The application of a normalized
absorbance ratio in function of time provided a graph that was similar to the
microbial growth curve. Application of FTIR in ATR mode to follow-up kinetics
during solid state fermentation seems to be a fast and easy alternative to
laborious measurement techniques, such as glucosamine determination.
PMID- 29339234
TI - Stoichiometric variation and loading capacity of a high-loading anammox attached
film expanded bed (AAEEB) reactor.
AB - The nitrogen loading rate (NLR) of an anammox attached film expanded bed (AAFEB)
reactor was increased from 5.0 to 60.0 gN/L/d. During the stable operational
period, the TN removal efficiency maintained at 87.3 +/- 2.5%, and a maximum
nitrogen removal rate (NRR) of 44.9 +/- 0.3 gN/L/d was achieved. Overload
resulted in the sharp deterioration of reactor performance, the ratio of
(Food/Microorganism)/SAA should be maintained at lower than 66 +/- 7% to ensure
the stable operation of the AAFEB reactor. New stoichiometric equations for the
anammox process under the low NLR condition (5.0 gN/L/d) and the high NLR
condition (50.0 gN/L/d) were proposed. The quantitative SAA-cytochrome heme C
relationship was established for the first time that providing a simple way for
monitoring the reactor performance. Substrate tolerance ability was significantly
increased that proving the stability of the AAFEB reactor was continuously
enhanced during the stable operational periods.
PMID- 29339235
TI - A highly efficient two-stage cultivation strategy for lutein production using
heterotrophic culture of Chlorella sorokiniana MB-1-M12.
AB - A heterotrophic mutant of Chlorella sorokiniana MB-1-M12 was evaluated for its
ability to produce lutein using organic carbon and nitrogen sources and without
light irradiation. In batch fermentation, the maximal lutein content (3.67 mg
lutein/g biomass) and productivity (2.84 mg/L/d) could be obtained when
cultivated in BG-11 medium with 7.5 g/L glucose, 0.75 g/L urea, pH 7.5 and a C/N
ratio of 10. A novel two-stage cultivation strategy that integrates fed-batch and
semi-batch operations was applied to enhance the lutein production performance.
When growing MB-1-M12 strain in a 5L fermenter using the optimal operation
strategies, the maximum biomass concentration, biomass productivity, lutein
content and lutein productivity could reach 25 g/L, 4.88 mg/L/d, 5.88 mg/g and
16.2 mg/L/d, respectively. This high lutein productivity could significantly
reduce the cultivation time and the associated costs, indicating the potential of
using MB-1-M12 strain for heterotrophic lutein production in commercial scale.
PMID- 29339236
TI - In-depth study of rice husk torrefaction: Characterization of solid, liquid and
gaseous products, oxygen migration and energy yield.
AB - Torrefaction is a promising method for biomass upgrading, and analysis of all
products is the essential way to reveal torrefaction mechanism. In this study,
torrefaction of rice husk was performed at 210-300 degrees C. Results showed
that the fuel properties of solid products were greatly enhanced upon removal of
oxygen. The gaseous products were mainly CO2 (52.9-73.8 vol%), followed by CO
(26.3-39.2 vol%). The liquid product was mainly water and some tar, and the
latter contained acids, furans, ketones, aldehydes, and phenols, among which the
relative content of acids was the highest. Torrefaction temperature has obvious
effects on the oxygen migration. Within the temperature range of 210-300 degrees
C, 9.5-63.2% of oxygen in rice husk was migrated to the gaseous and liquid
products. The H2O was the major contributor to deoxygenation, followed by CO2 and
CO. Thus, formation of H2O, CO2, and CO during torrefaction is important as it
achieves the purpose of intense deoxygenation.
PMID- 29339238
TI - Topical betaxolol for treating relapsing paronychia with pyogenic granuloma-like
lesions induced by epidermal growth factor receptor inhibitors.
PMID- 29339237
TI - Assessing the outcomes, risks, and costs of local versus general anesthesia: A
review with implications for cutaneous surgery.
AB - BACKGROUND: There is a paucity of data providing direct comparison of outcomes,
complications, and costs between general and local anesthesia in cutaneous
surgery. OBJECTIVE: Analyze the literature from dermatologic and other
specialties to compare outcomes, risks, and costs of general and local
anesthesia. METHODS: A retrospective analysis of case comparison studies from
other specialties comparing outcomes, risks, and/or costs in local versus general
anesthesia was performed. A review of the literature from dermatology and other
specialties was included. RESULTS: A total of 51 studies were selected; 41 of
them directly examined outcomes in procedures performed under local and general
anesthesia, and none found a significant difference in outcomes. A total of 41
studies measured adverse effects. Of these, 15 studies (36.6%) report
significantly better outcomes between the 2 techniques. Only 2 studies (4.9%)
report significantly improved outcomes with use of general anesthesia; 15 of 36
studies (41.7%) report fewer adverse events in local anesthesia. Of the 13
studies that examined costs, all (100%) found significantly decreased costs with
use of local anesthesia. LIMITATIONS: These data cannot be seamlessly applied to
all cases of cutaneous surgery. CONCLUSION: Local anesthesia techniques provide
outcomes equal to or better than general anesthesia and with significantly lower
costs.
PMID- 29339239
TI - Multiple melanonychia striata as a sign of connective tissue disorders.
PMID- 29339240
TI - Prevalence of type 2 diabetes mellitus among patients with hidradenitis
suppurativa in the United States.
AB - BACKGROUND: Few studies have evaluated the relationship between hidradenitis
suppurativa (HS) and type 2 diabetes mellitus (T2DM), and the existing data show
conflicting results. OBJECTIVE: To determine the prevalence of T2DM among
patients with HS and identify at-risk demographic subgroups. METHODS: Cross
sectional analysis identifying T2DM among patients with and without HS from a
demographically heterogeneous population-based sample of more than 50 million
patients in the United States. RESULTS: The overall prevalence of T2DM among
patients with HS was 24.8% (10,705 of 43,105) compared with 15.6% (1,993,320 of
12,527,570) among patients without HS. The prevalence was highest among patients
with HS who were male (3045 of 10,785 [28.2%]), older (1945 of 3950 [49.2%]),
nonwhite (4665 of 17,495 [26.7%]), obese (9065 of 30,855 [29.4%]), tobacco
smokers (6880 of 25,005 [27.5%]), hypertensive (8595 of 19,610 [43.8%]), and
hyperlipidemic (7965 of 17,190 [46.3%]). In univariable and multivariable
analyses, patients with HS had 1.75 (95% confidence interval [CI], 1.71-1.79) and
1.58 (95% CI, 1.54-1.62) times the odds, respectively, of having T2DM. HS was
associated with T2DM across all demographic subgroups. The association was
stronger for younger patients (an OR of 1.67 and 95% CI of 1.60-1.72 for ages 18
44 years vs an OR of 1.50 and 95% CI of 1.41-1.61 for ages >=65 years).
LIMITATIONS: We lacked information on HS disease severity. CONCLUSION: Patients
with HS with risk factors, signs, or symptoms of T2DM should be screened.
PMID- 29339241
TI - Role of graft-versus-host disease in the development of secondary skin cancers in
hematopoietic stem cell transplant recipients: A meta-analysis.
PMID- 29339242
TI - Combined acitretin and Candida antigen versus either agent alone in the treatment
of recalcitrant warts.
PMID- 29339243
TI - Black dots in palmoplantar warts-challenging a concept: A histopathologic study.
PMID- 29339244
TI - Epigenetics of breast cancer: Biology and clinical implication in the era of
precision medicine.
AB - In the last years, mortality from breast cancer has declined in western countries
as a consequence of a more widespread screening resulting in earlier detection,
as well as an improved molecular classification and advances in adjuvant
treatment. Nevertheless, approximately one third of breast cancer patients will
develop distant metastases and eventually die for the disease. There is now a
compelling body of evidence suggesting that epigenetic modifications comprising
DNA methylation and chromatin remodeling play a pivotal role since the early
stages of breast cancerogenesis. In addition, recently, increasing emphasis is
being placed on the property of ncRNAs to finely control gene expression at
multiple levels by interacting with a wide array of molecules such that they
might be designated as epigenetic modifiers. In this review, we summarize the
current knowledge about the involvement of epigenetic modifications in breast
cancer, and provide an overview of the significant association of epigenetic
traits with the breast cancer clinicopathological features, emphasizing the
potentiality of epigenetic marks to become biomarkers in the context of precision
medicine.
PMID- 29339245
TI - Systematic review and evaluation of aspartame carcinogenicity bioassays using
quality criteria.
AB - The current review assessed cancer studies of aspartame based on a quality
appraisal using the Klimisch grading system. Nine studies having complete
histopathology were included: three 2-year studies by Searle; three transgenic
mice studies by the NTP; three lifetime studies by the Ramazzini Institute. A
tenth study limited to brain tumors was not rated. None were determined as
Klimisch Code 1 (reliable without restrictions). The Searle studies predated GLP
standards but their methodology was comparable; transgenic mouse models are not
validated, but are accepted as supporting data. These studies were rated Klimisch
Code 2 (reliable with restrictions). The Ramazzini Institute used a lifetime
model of their own design that has been questioned due to high rates of
spontaneous tumors, issues with tumor type diagnosis and concerns about the
impact of chronic infections. As many of these problems could be attributed to
using animals that died or were terminated near end of life, along with the other
problems noted, these studies were rated Klimisch Code 3 (not reliable). As the
Klimisch Code 2 studies demonstrated a lack of carcinogenic potential, and as
aspartame is hydrolyzed to common components and lacks genotoxic activity, a
conclusion that aspartame is not carcinogenic is supported.
PMID- 29339246
TI - Absence of toxicity in Swiss mice following treatment with 7-acetoxy-4-aryl-3,4
dihydrocoumarin: Acute and repeated-dose toxicity study.
AB - Neoflavonoids, which are classified as 4-arylcoumarin (neoflavone), 3,4-dihydro-4
arylcoumarin and neoflavene, have been the subject of a number of studies with
respect to their therapeutic potential and, despite promising in vitro, ex vivo
and in vivo pharmacological activities, there is a lack of studies demonstrating
their toxicological properties. Therefore, this study aims to evaluate the acute
(14 days) and repeated-dose (28 days) toxicity of synthetic neoflavonoid 7
acetoxy-4-aryl-3,4-dihydrocoumarin in Swiss mice through parameters related to
changes in body weight, food and water intake, hematological and biochemical
parameters. Toxicity studies using acute doses (300 and 2000 mg/kg) and repeated
doses (250, 500 and 1000 mg/kg) orally were carried out as per Organization for
Economic Co-operation and Development (OECD) guidelines 423 and 407,
respectively. Based on the results of this study, treatment with 7-acetoxy-4-aryl
3,4-dihydrocoumarin was found to not cause clinical adverse symptoms and
mortality in any animal used in the acute and repeated-dose toxicity study. In
addition, no significant changes were observed in body weight and internal
organs, food and water intake, hematological and biochemical parameters, compared
to control group. Therefore, these results provide an initial understanding
regarding the toxicity profile of 7-acetoxy-4-aryl-3,4-dihydrocoumarin, which can
be considered a neoflavonoid with toxicity seen at doses higher than 2000 mg/kg
in Swiss mice.
PMID- 29339247
TI - Self-emulsifying peptide drug delivery systems: How to make them highly mucus
permeating.
AB - AIM: It was the aim of this study to evaluate the mucus permeating properties of
self-emulsifying drug delivery systems (SEDDS) exhibiting different size and zeta
potential. METHODS: Various SEDDS were prepared and characterized regarding
droplet size, zeta potential and stability. Desmopressin was incorporated as
model peptide drug and log P (SEDDS/water) was determined. Thereafter, mucus
permeation studies with freshly isolated porcine mucus via Transwell method were
performed. Moreover, the impact of water movement on mucus permeation of SEDDS
was investigated. Different types of nanocarriers including nanoparticles and
liposomes served as references. RESULTS: SEDDS exhibited an initial droplet size
of 25.0 +/- 2.2, 49.5 +/- 4.6, 123.5 +/- 12.1, 226.2 +/- 93.4 and 502.9 +/- 93.7
nm and a zeta potential of +24.4 +/- 4.6, +10.6 +/- 2.0, 0.2 +/- 3.8, -8.2 +/-
3.4 and -35.1 +/- 2.7 mV. Log P was in the range of 1.29-2.09 and mucus
permeation studies with these SEDDS revealed a clear correlation between droplet
size and permeation rate. The smaller SEDDS were, the higher their mucus
permeating properties were. Negatively charged SEDDS demonstrated a higher
permeation rate than positively charged SEDDS. In comparison to liposomes and
solid nanocarriers SEDDS exhibited up to 5-fold higher mucus permeating
properties. CONCLUSION: Small droplet size and negative zeta potential of SEDDS
could be identified as key parameters for their mucus permeating properties.
PMID- 29339248
TI - Recent trends of nanomedicinal approaches in clinics.
AB - Nanotechnology has become the indispensable cutting edge science providing
solutions to many problems associated with human being. The application of
nanotechnology associated to human health "nanomedicine" has revolutionized the
drug delivery system by providing improved pharmacological and therapeutic
properties of drugs. These advantageous effects of drug loaded nanocarrier
systems are embraced by the pharmaceutical industries for the development of
different effective nanocarriers. Currently, several drug loaded nanoformulations
are approved by the Food and Drug Administration (FDA), and some of them are
undergoing clinical trials for the human use. In this review, we have discussed
the progress achieved so far for various drug loaded nanoformulations along with
few emerging nanoformulations that are about to enter into clinical trials.
PMID- 29339249
TI - Semifluorinated alkane based systems for enhanced corneal penetration of poorly
soluble drugs.
AB - Semifluorinated alkanes (SFAs) are amphiphilic liquids that can dissolve
hydrophobic drugs to form clear solutions. This study evaluated the potential of
two SFAs to act as vehicle for topical ocular drug delivery. After confirming
ocular safety, an ex vivo corneal penetration model was developed to determine
drug distribution and corneal bioavailability. Hydrophobic dye distribution in
the different corneal layers was visualised under a confocal microscope. Corneal
bioavailability of cyclosporine A (CsA) dissolved in perfluorobutylpentane (F4H5)
or perfluorohexyloctane (F6H8) was compared to commercially available CsA
ophthalmic emulsions, Restasis(r) and Ikervis(r). Precorneal residence of the
four test vehicles containing the hydrophobic dye was also compared using an ex
vivo corneal tissue model. Preferential accumulation of the hydrophobic dye in
the corneal epithelium was observed with higher amounts detectable when delivered
via the SFAs compared to Restasis or Ikervis. A significant improvement in
corneal CsA penetration was observed after application of a single dose of 0.05%
CsA in F4H5 and F6H8 when compared to Restasis with the area under curve over 4 h
(AUC(0-4h)) being at least 8-fold greater for both SFAs (p < .0001). Moreover,
the AUC(0-4h) of 0.1% CsA in F4H5 was almost 5-fold greater than Ikervis (p <
.0001). Finally, the precorneal residence time of both SFA solutions was
significantly longer than that of the commercial emulsions with the AUC(0-60min)
being 2- to 11-fold greater. This study demonstrated that SFAs can significantly
improve the local bioavailability of hydrophobic drugs by increasing corneal
penetration as well as prolonging precorneal residence. They therefore offer a
promising new platform for topical drug delivery to the eye.
PMID- 29339250
TI - Discovery of novel HSP90 inhibitors that induced apoptosis and impaired
autophagic flux in A549 lung cancer cells.
AB - Heat shock protein 90 (HSP90) inhibition has aroused increasing enthusiasm in
antitumor strategies in recent years. According to our previous studies, we
synthesized a series of coumarin pyrazoline compounds HCP1-HCP6 that might be
HSP90 inhibitors. Interactions between HCP1-HCP6 and HSP90 were examined and
antitumor activities of them were investigated in A549 lung cancer cells. Results
showed that all the six derivatives could interact with HSP90, in which HCP1
exhibited the best binding ability and inhibited the activity of HSP90.
Meanwhile, HCP1-HCP6 reduced the cell viability of A549 cells and HCP1 possessed
the lowest IC50 value. Above all HCP1 exerted better HSP90 inhibitory and
anticancer effects than our initially identified HSP90 inhibitor DPB. As to the
underlying mechanism, HCP1-HCP6 not only induced apoptosis as DPB but also
blocked autophagic flux in A549 cells. Therefore, we discovered a novel HSP90
inhibitor HCP1 that had better biological activity and provided us a useful tool
to explore the underlying mechanism of lung cancer therapy.
PMID- 29339251
TI - Quinoxaline derivatives as new inhibitors of coxsackievirus B5.
AB - Enteroviruses are among the most common and important human pathogens for which
there are no specific antiviral agents approved by the US Food and Drug
Administration so far. Particularly, coxsackievirus infections have a worldwide
distribution and can cause many important diseases. We here report the synthesis
of new 14 quinoxaline derivatives and the evaluation of their cytotoxicity and
antiviral activity against representatives of ssRNA, dsRNA and dsDNA viruses.
Promisingly, three compounds showed a very potent and selective antiviral
activity against coxsackievirus B5, with EC50 in the sub-micromolar range (0.3
0.06 MUM). A combination of experimental techniques (i.e. virucidal activity,
time of drug addition and adsorption assays) and in silico modeling studies were
further performed, aiming to understand the mode of action of the most active,
selective and not cytotoxic compound, the ethyl 4-[(2,3-dimethoxyquinoxalin-6
yl)methylthio]benzoate (6).
PMID- 29339252
TI - Structure-based design of human immuno- and constitutive proteasomes inhibitors.
AB - Starting from the X-ray structure of our previous tripeptidic linear mimics of
TMC-95A in complex with yeast 20S proteasome, we introduced new structural
features to induce a differential inhibition between human constitutive and
immunoproteasome 20S particles. Libraries of 24 tripeptidic and 6 dipeptidic
derivatives were synthesized. The optimized preparation of 3-hydroxyoxindolyl
alanine residues from tryptophan and their incorporation in peptides were
described. Several potent inhibitors of human constitutive proteasome and
immunoproteasome acting at the nanomolar level (IC50 = 7.1 nM against the
chymotrypsin-like activity for the best inhibitor) were obtained. A cytotoxic
effect at the submicromolar level was observed against 6 human cancer cell lines.
PMID- 29339253
TI - Design, synthesis and bioevalucation of novel 2,3-dihydro-1H-inden-1-amine
derivatives as potent and selective human monoamine oxidase B inhibitors based on
rasagiline.
AB - Parkinson's disease (PD) is associated with elevated levels of hMAO-B in the
brain, and MAO-B has been recognized a successful target for developing anti-PD
drugs. Herein we report rasagiline derivatives as novel potent and selective hMAO
B inhibitors. They were designed by employing fragment-based drug design strategy
to link rasagiline and hydrophobic fragments, which may target a hydrophobic
pocket in the entrance cavity of hMAO-B. Different linkers such as -OCH2-, -SCH2
, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2CH2O- were tried. A promising selective hMAO-B
inhibitor D14 with similar inhibitory activity as rasagiline and improved isoform
selectivity was yielded. The selectivity profile of compounds reported herein
suggests that we can further develop more potent hMAO-B inhibitors with high
isoform selectivity through this strategy.
PMID- 29339254
TI - Design, synthesis, biological evaluation and docking studies of new 3-(4,5
dihydro-1H-pyrazol/isoxazol-5-yl)-2-phenyl-1H-indole derivatives as potent
antioxidants and 15-lipoxygenase inhibitors.
AB - New candidates of 3-(4,5-dihydro-1H-pyrazol/isoxazol-5-yl)-2-phenyl-1H-indole
derivatives (4-7) were designed combining the pyrazoline/isoxazoline heterocycles
and 2-phenylindole to explore its potential as 15-lipoxygenase (15-LOX)
inhibitors. The design of the new derivatives was based on utilizing the
antioxidant properties of pyrazoline, 2-phenylindole and the good 15-LOX
inhibition properties of indolylpyrazoline. The derivatives were synthesized
adopting simple and laboratory friendly reaction conditions to give the target
compounds in quantitative yields. The resulting indolylpyrazolines/isoxazolines
were evaluated as antioxidants against 2,2-diphenyl-1-picrylhydrazyl (DPPH),
nitric oxide (NO) and superoxide dismutase (SOD); indolylpyrazoline (4b) was the
most potent antioxidant against SOD assay (IC50 = 1.78 MUM) to be superior to
ascorbic by 2 folds. Consistently, (4b) was the most potent inhibitor when tested
against Soybean 15-LOX (IC50 = 3.84 MUM) excelling quercetin as standard
inhibitor by 1.8 folds. Some of the new derivatives were docked into the active
binding site of human 15-LOX (PDB entry 4NRE) emphasizing the most potent
derivative (4b) and the least potent one (4c). Docking solutions of compounds
(4b), (4c), (5b) and (6c) revealed that (4b) was the only compound that got
stabilized into the catalytic pocket of enzyme by pi-cation interaction with the
catalytic Fe+ and formation of one hydrogen bond with Ile 676 amino acid. Other
derivatives including the least potent one variably got stabilized into the
active binding pocket by pi-cation interaction with the catalytic Fe+ but failed
to form hydrogen bond with Ile 676. For the future optimization of the generated
inhibitors, (i) antioxidant activity against SOD, (ii) the inhibitor
stabilization by pi-cation interaction with the catalytic Fe+3 and (iii)
formation of hydrogen bond with Ile 676 should be regarded.
PMID- 29339255
TI - Design, synthesis and biological evaluation of LX2343 derivatives as
neuroprotective agents for the treatment of Alzheimer's disease.
AB - A series of LX2343 derivatives were designed, synthesized and evaluated as
neuroprotective agents for Alzheimer's disease (AD) in vitro. Most of the
compounds displayed potent neuroprotective activities. Especially for compound
A6, exhibited a remarkable EC50 value of 0.22 MUM. Further investigation
demonstrated that compound A6 can significantly reduce Abeta production and
increase Abeta clearance, and alleviate Tau hyperphosphorylation. Most
importantly, compound A6 could ameliorate learning and memory impairments in
APP/PS1 transgenic mice. The present study evidently showed that compound A6 is a
potent neuroprotective agent and might serve as a promising lead candidate for
the treatment of Alzheimer's disease.
PMID- 29339256
TI - The PBII gene of the human salivary proline-rich protein P-B produces another
protein, Q504X8, with an opiorphin homolog, QRGPR.
AB - OBJECTIVES: The NCBI gene database and human-transcriptome database for
alternative splicing were used to determine the expression of mRNAs for P-B
(SMR3B) and variant form of P-B. The translational product from the former mRNA
was identified as the protein named P-B, whereas that from the latter has not yet
been elucidated. In the present study, we investigated the expression of P-B and
its variant form at the protein level. DESIGN: To identify the variant protein of
P-B, (1) cationic proteins with a higher isoelectric point in human pooled whole
saliva were purified by a two dimensional liquid chromatography; (2) the peptide
fragments generated from the in-solution of all proteins digested with trypsin
separated and analyzed by MALDI-TOF-MS; and (3) the presence or absence of P-B in
individual saliva was examined by 15% SDS-PAGE. RESULTS: The peptide sequences
(I37PPPYSCTPNMNNCSR52, C53HHHHKRHHYPCNYCFCYPK72, R59HHYPCNYCFCYPK72 and
H60HYPCNYCFCYPK72) present in the variant protein of P-B were identified. The
peptide sequence (G6PYPPGPLAPPQPFGPGFVPPPPPPPYGPGR36) in P-B (or the variant) and
sequence (I37PPPPPAPYGPGIFPPPPPQP57) in P-B were identified. The sum of the
sequences identified indicated a 91.23% sequence identity for P-B and 79.76% for
the variant. There were cases in which P-B existed in individual saliva, but
there were cases in which it did not exist in individual saliva. CONCLUSIONS: The
variant protein is produced by excising a non-canonical intron (CC-AC pair) from
the 3'-noncoding sequence of the PBII gene. Both P-B and the variant are subject
to proteolysis in the oral cavity.
PMID- 29339257
TI - Changes in the concentrations of inflammatory and oxidative status biomediators
(MIP-1 alpha, PMN elastase, MDA, and IL-12) in depressed patients with and
without posttraumatic stress disorder.
AB - BACKGROUND: Both proinflammatory cytokines and oxidative stress are considered an
imbalance between the cellular production of reactive oxygen species and the
antioxidant defense mechanisms. An inflammatory response that occurs in
depression leads to a synergy between pro-inflammatory cytokines and oxidative
stress. This synergy induces common signal transduction pathways that boost the
inflammatory cascade. The object of this study was to assess the concentrations
of inflammatory and oxidative status biomediators such as MIP-1alpha, PMN
elastase, MDA, and IL-12 in depressed patients with and without posttraumatic
stress disorder (PTSD), and with PTSD alone. METHODS: The number of participants
enrolled in the study was 460. Out of them, 420 were determined to be suffering
from depression, and 40 (20 males and 20 females) comprised the control group.
The subjects were divided into groups, each consisting of 60 participants (30
males and 30 females) with: mild depression (MD), moderate depression (MOD),
severe depression (SeD), MD and PTSD (MD+PTSD), MOD and PTSD (MOD+PTSD), SeD and
PTSD (Sed+PTSD), and PTSD alone. At 7:00 a.m. all patients had blood samples
collected to assess serum concentrations of the studied parameters using the
Elisa method. RESULTS: Depression became more severe as the concentration levels
of MIP-1alpha, PMN elastase, MDA, and IL-12 changed. CONCLUSION: Studied
parameters can be used as markers of chronic stress in both depression and PTSD,
either comorbid or alone, to make an early diagnosis and evaluate disease
severity. Revealed changes confirm the presence of a biological response in
depression.
PMID- 29339258
TI - Relationship between very early brain structure and neuromotor, neurological and
neurobehavioral function in infants born <31 weeks gestational age.
AB - AIM: This study aimed to examine associations between structural MRI and
concurrent motor, neurological and neurobehavioral measures at 30-32 weeks
postmenstrual age (PMA; 'Early'), and at term equivalent age ('Term'). METHOD: In
this prospective cohort study, infants underwent Early MRI (n = 119; 73 male;
median 32 weeks 1 day PMA) and Term MRI (n = 102; 61 male; median 40 weeks 4 days
PMA) at 3 T. Structural images were scored generating white matter (WM), cortical
gray matter, deep gray matter, cerebellar and global brain abnormality scores.
Clinical measures were General Movements Assessment (GMs), Hammersmith Neonatal
Neurological Examination (HNNE) and NICU Neonatal Neurobehavioral Scale (NNNS).
The Premie-Neuro was administered Early and the Test of Infant Motor Performance
(TIMP) and a visual assessment at Term. RESULTS: Early MRI cerebellar scores were
strongly associated with neurological components of HNNE (reflexes), NNNS
(Hypertonicity), the Premie-Neuro neurological subscale (regression coefficient
beta = -0.06; 95% confidence interval CI = -0.09, -0.04; p < .001) and cramped
synchronized GMs (beta = 1.10; 95%CI = 0.57, 1.63; p < .001). Term MRI WM and
global scores were strongly associated with the TIMP (WM beta = -1.02; 95%CI =
1.67, -0.36; p = .002; global beta = -1.59; 95%CI = -2.62, -0.56; p = .001).
INTERPRETATION: Brain structure on Early and Term MRI was associated with
concurrent motor, neurological and neurobehavioral function in very preterm
infants.
PMID- 29339259
TI - Perturbations of gut microbiome genes in infants with atopic dermatitis according
to feeding type.
AB - BACKGROUND: Perturbations of the infant gut microbiota can shape development of
the immune system and link to the risk of allergic diseases. OBJECTIVE: We sought
to understand the role of the gut microbiome in patients with atopic dermatitis
(AD). The metagenome of the infant gut microbiome was analyzed according to
feeding types. METHODS: Composition of the gut microbiota was analyzed in fecal
samples from 129 infants (6 months old) by using pyrosequencing, including 66
healthy infants and 63 infants with AD. The functional profile of the gut
microbiome was analyzed by means of whole-metagenome sequencing (20 control
subjects and 20 patients with AD). In addition, the total number of bacteria in
the feces was determined by using real-time PCR. RESULTS: The gut microbiome of 6
month-old infants was different based on feeding types, and 2 microbiota groups
(Bifidobacterium species-dominated and Escherichia/Veillonella species-dominated
groups) were found in breast-fed and mixed-fed infants. Bacterial cell amounts in
the feces were lower in infants with AD than in control infants. Although no
specific taxa directly correlated with AD in 16S rRNA gene results, whole
metagenome analysis revealed differences in functional genes related to immune
development. The reduction in genes for oxidative phosphorylation,
phosphatidylinositol 3-kinase-Akt signaling, estrogen signaling, nucleotide
binding domain-like receptor signaling, and antigen processing and presentation
induced by reduced colonization of mucin-degrading bacteria (Akkermansia
muciniphila, Ruminococcus gnavus, and Lachnospiraceae bacterium 2_1_58FAA) was
significantly associated with stunted immune development in the AD group compared
with the control group (P < .05). CONCLUSIONS: Alterations in the gut microbiome
can be associated with AD because of different bacterial genes that can modulate
host immune cell function.
PMID- 29339261
TI - Mumps infection but not childhood vaccination induces persistent polyfunctional
CD8+ T-cell memory.
PMID- 29339260
TI - The complement system in the airway epithelium: An overlooked host defense
mechanism and therapeutic target?
PMID- 29339262
TI - The long-term physical and psychological health impacts of flooding: A systematic
mapping.
AB - BACKGROUND: Flooding has caused significant and wide ranging long-term health
impacts for affected populations. However, until now, the long-term health
outcomes, epidemiological trends and specific impact factors of flooding had not
been identified. In this study, the relevant literature was systematically mapped
to create the first synthesis of the evidence of the long-term health impacts of
flooding. METHODS: The systematic mapping method was used to collect and
categorize all the relevant literature. A study was included if it had a
description or measurement of health impacts over six months after flooding. The
search was limited to peer reviewed articles and grey literature written in
English, published from 1996 to 2016. RESULTS: A total of 56 critical articles
were extracted for the final map, including 5 qualitative and 51 quantitative
studies. Most long-term studies investigated the psychological impacts of
flooding, including PTSD, depression, anxiety, psychiatric disorders, sleep
disorder and suicide. Others investigated the physiological impacts, including
health-related quality of life, acute myocardial infarction, chronic diseases,
and malnutrition. Social support was proved to be protective factors that can
improve health outcomes in the long-term after flooding. To date, there have been
relatively few reviews had focused on the long-term health impacts of flooding.
This study coded and catalogued the existing evidence across a wide range of
variables and described the long-term health consequences within a conceptual
map. DISCUSSION AND CONCLUSIONS: Although there was no boundary between the short
term and the long-term impacts of flooding, the identified health outcomes in
this systematic mapping could be used to define long-term health impacts. The
studies showed that the prevalence of psychological diseases had a reversed
increasing trend occurred even in the long-term in relatively poor post-flooding
environments. Further cohort or longitudinal research focused on disability,
chronic diseases, relocation population, and social interventions after flooding,
are urgently required.
PMID- 29339263
TI - Impact of organic amendments (biochar, compost and peat) on Cd and Zn mobility
and solubility in contaminated soil of the Campine region after three years.
AB - To determine the long-term impact of organic amendments on metal (Cd and Zn)
immobilization, soil from the Campine region was amended with holm oak-derived
biochar, compost, and peat, and monitored over a 3-year period. Pot experiments
were conducted by mixing the amendments independently at 2% and 4% (g/g) with the
soil. The mobility and solubility of metals in the treatments were assessed by
means of rhizon soil moisture samplers, sequential BCR extractions, and diffusive
gradient in thin films (DGT). Over the three-year period, the 2% biochar addition
resulted in an average decrease in pore water concentration of 40% for Cd and 48%
for Zn whereas the 4% addition led to an average decrease of 66% for Cd and 77%
for Zn. The immobilization effect in the biochar treatments was attributed to the
consistently higher pH and lower concentrations of dissolved organic carbon (DOC)
in the soil. The latter may have been caused by sorption of DOC onto the surface
of biochar thereby increasing its negatively charged functional groups that are
able to sorb cations. On the other hand, compost and peat had the unwanted effect
of significantly increasing the concentrations of Cd and Zn in the soil pore
water. This was partly due to the formation of soluble organo-metallic complexes
as significantly higher DOC concentrations were found in the compost and peat
treatments. Results from the DGT measurements, after a 24 h deployment time,
revealed a low resupply (R <= 0.4) of Cd and Zn from the solid phase to the soil
solution in both amended and unamended soil. This suggests a case of slow metal
desorption kinetics in the soil that was relatively unchanged by the presence of
organic amendments.
PMID- 29339264
TI - Source apportionment of soil heavy metals using robust absolute principal
component scores-robust geographically weighted regression (RAPCS-RGWR) receptor
model.
AB - The traditional source apportionment models, such as absolute principal component
scores-multiple linear regression (APCS-MLR), are usually susceptible to
outliers, which may be widely present in the regional geochemical dataset.
Furthermore, the models are merely built on variable space instead of
geographical space and thus cannot effectively capture the local spatial
characteristics of each source contributions. To overcome the limitations, a new
receptor model, robust absolute principal component scores-robust geographically
weighted regression (RAPCS-RGWR), was proposed based on the traditional APCS-MLR
model. Then, the new method was applied to the source apportionment of soil metal
elements in a region of Wuhan City, China as a case study. Evaluations revealed
that: (i) RAPCS-RGWR model had better performance than APCS-MLR model in the
identification of the major sources of soil metal elements, and (ii) source
contributions estimated by RAPCS-RGWR model were more close to the true soil
metal concentrations than that estimated by APCS-MLR model. It is shown that the
proposed RAPCS-RGWR model is a more effective source apportionment method than
APCS-MLR (i.e., non-robust and global model) in dealing with the regional
geochemical dataset.
PMID- 29339265
TI - Spatio-temporal distribution of soil nitrogen in Poyang lake ecological economic
zone (South-China).
AB - Revealing the spatio-temporal distribution of soil nitrogen (N) contributes to N
management and prevention of N pollution. The objective of this work is to study
the spatio-temporal distribution of soil N and their driving factors in the
topsoil (0-20 cm) of farmland in Yugan county, China in 1982 and 2012. Data were
collected from 200 sampling sites of the second national soil survey in Yugan in
1982 and 423 sampling sites of the soil testing and formula fertilization project
in 2012. On average total N (TN) and available N (AN) significantly increased
from 1.50 g kg-1 and 153.04 mg kg-1 in 1982 to 1.58 g kg-1 and 179.75 mg kg-1 in
2012, respectively. The distance of spatial autocorrelation for TN increased from
2.79 to 6.18 km and from 2.97 to 18.00 km for AN from 1982 to 2012. The
nugget/sill ratio for TN (0.472 in 1982 and 0.581 in 2012) indicated that soil TN
driving by natural characteristics in 1982 to human activities in 2012. The
nugget/sill ratio for soil AN (0.471 in 1982 and 0.688 in 2012) indicated that
soil AN is more influenced by human activities. The major factors driving the
spatio-temporal distribution of soil N was N application rate. To promote the
sustainable development of agriculture and eco-environment, we should improve the
awareness of farmers on chemical fertilizers (particularly N) and the level of N
fertilizer management, increase the use of manure and organic fertilizer and
facilitate rational fertilization by farmers.
PMID- 29339266
TI - Long-term trend analysis on total and extreme precipitation over Shasta Dam
watershed.
AB - California's interconnected water system is one of the most advanced water
management systems in the world, and understanding of long-term trends in
atmospheric and hydrologic behavior has increasingly being seen as vital to its
future well-being. Knowledge of such trends is hampered by the lack of long
period observation data and the uncertainty surrounding future projections of
atmospheric models. This study examines historical precipitation trends over the
Shasta Dam watershed (SDW), which lies upstream of one of the most important
components of California's water system, Shasta Dam, using a dynamical
downscaling methodology that can produce atmospheric data at fine time-space
scales. The Weather Research and Forecasting (WRF) model is employed to
reconstruct 159years of long-term hourly precipitation data at 3km spatial
resolution over SDW using the 20th Century Reanalysis Version 2c dataset. Trend
analysis on this data indicates a significant increase in total precipitation as
well as a growing intensity of extreme events such as 1, 6, 12, 24, 48, and 72
hour storms over the period of 1851 to 2010. The turning point of the increasing
trend and no significant trend periods is found to be 1940 for annual
precipitation and the period of 1950 to 1960 for extreme precipitation using the
sequential Mann-Kendall test. Based on these analysis, we find the trends at the
regional scale do not necessarily apply to the watershed-scale. The sharp
increase in the variability of annual precipitation since 1970s is also detected,
which implies an increase in the occurrence of extreme wet and dry conditions.
These results inform long-term planning decisions regarding the future of Shasta
Dam and California's water system.
PMID- 29339267
TI - Effects of exotic plantation forests on soil edaphon and organic matter
fractions.
AB - There is uncertainty and limited knowledge regarding soil microbial properties
and organic matter fractions of natural secondary forest accompanying chemical
environmental changes of replacement by pure alien plantation forests in a hilly
area of southwest of Sichuan province China. The aim of this study was to
evaluate the impact of natural secondary forest (NSF) to pure Cryptomeria
fortunei forest (CFF) and Cunninghamia lanceolata forest (CLF) on soil organic
fractions and microbial communities. The results showed that the soil total
phospholipid fatty acids (PLFAs), total bacteria and fungi, microbial carbon
pool, organic recalcitrant carbon (C) and (N) fractions, soil microbial quotient
and labile and recalcitrant C use efficiencies in each pure plantation were
significantly decreased, but their microbial N pool, labile C and N pools, soil
carbon dioxide efflux, soil respiratory quotient and recalcitrant N use
efficiency were increased. An RDA analysis revealed that soil total PLFAs, total
bacteria and fungi and total Gram-positive and Gram-negative bacteria were
significantly associated with exchangeable Al3+, exchangeable acid, Al3+,
available P and Mg2+ and pH, which resulted into microbial functional changes of
soil labile and recalcitrant substrate use efficiencies. Modified microbial C-
and N-use efficiency due to forest conversion ultimately meets those of rapidly
growing trees in plantation forests. Enlarged soil labile fractions and soil
respiratory quotients in plantation forests would be a potential positive effect
for C source in the future forest management. Altogether, pure plantation
practices could provoke regulatory networks and functions of soil microbes and
enzyme activities, consequently leading to differentiated utilization of soil
organic matter fractions accompanying the change in environmental factors.
PMID- 29339268
TI - Incidence of Second Primary Malignancies after Autologous Transplantation for
Multiple Myeloma in the Era of Novel Agents.
AB - The advent of novel agents for multiple myeloma (MM) is cause for a re
examination of the incidence of second primary malignancies (SPMs). We examined
the SPM rate in MM patients who were enrolled in the prospective observational
CALM (Collaboration to Collect Autologous Transplant outcome in Lymphoma and
Myeloma) study. Between 2008 and 2012, 3204 patients with MM underwent a first
autologous hematopoietic stem cell transplantation. Plerixafor was used as a
mobilizing agent for patients with poor (or potentially poor) stem cell
mobilization as defined by the respective centers. A total of 135 patients
developed SPMs, with a cumulative incidence of 5.3% (95% confidence interval, 4.4
to 6.3) at 72 months. Ninety-four patients developed solid tumors, 30 developed
hematologic malignancies, and 11 developed an SPM of an unknown type. The
cumulative incidence of known hematologic and solid malignancies were 1.4% and
3.6%, respectively, at 72 months. In a univariate analysis, use of radiotherapy,
type of induction regimen, hematopoietic stem cell dose, poor mobilizer status,
plerixafor use, and sex did not influence the cumulative incidence of SPMs. Only
age over 65 years was statistically associated with an increased incidence.
Overall, the incidence of SPMs was comparable to earlier estimations of SPMs in
MM.
PMID- 29339269
TI - Phase 2 Study of an Intravenous Busulfan and Melphalan Conditioning Regimen for
Autologous Stem Cell Transplantation in Patients with Multiple Myeloma (KMM150).
AB - This prospective study evaluated the efficacy and toxicity of intravenous
busulfan and melphalan as a conditioning regimen for autologous stem cell
transplantation (ASCT) in patients with multiple myeloma (MM). A total of 99
patients with MM, enrolled between January 2013 and March 2016, received
intravenous busulfan (9.6 mg/kg) and melphalan (140 mg/m2) before ASCT. The
median time to transplant was 6.2 months, and 90 (90.9%) patients underwent ASCT
within 12 months of the diagnosis. The overall response rate after ASCT was
94.0%, including 43.5% with a stringent complete response/complete response,
27.3% with very good partial response, and 23.2% with partial response. The most
common severe nonhematologic toxicity (grade 3 to 4) was infection (26.3%) and
stomatitis (15.2%). Three (3.2%) patients developed veno-occlusive disease. No
treatment-related mortality was observed. After a median follow-up of 26.1
months, the median progression-free survival was 27.2 months (range, 13.0 to 41.4
months) and median overall survival was not reached. In conclusion, a
conditioning regimen of intravenous busulfan and melphalan was effective and
tolerable. ClinicalTrials.gov. number: NCT01923935.
PMID- 29339270
TI - Proceedings From the Fourth Haploidentical Stem Cell Transplantation Symposium
(HAPLO2016), San Diego, California, December 1, 2016.
AB - The resurgence of haploidentical stem cell transplantation (HaploSCT) over the
last decade is one of the most important advances in the field of hematopoietic
stem cell transplantation (HSCT). The modified platforms of T cell depletion
either ex vivo (CD34+ cell selection, "megadoses" of purified CD34+ cells, or
selective depletion of T cells) or newer platforms of in vivo depletion of T
cells, with either post-transplantation high-dose cyclophosphamide or intensified
immune suppression, have contributed to better outcomes, with survival similar to
that in HLA-matched donor transplantation. Further efforts are underway to
control viral reactivation using modified T cells, improve immunologic
reconstitution, and decrease the relapse rate post-transplantation using donor
derived cellular therapy products, such as genetically modified donor lymphocytes
and natural killer cells. Improvements in treatment-related mortality have
allowed the extension of haploidentical donor transplants to patients with
hemoglobinopathies, such as thalassemia and sickle cell disease, and the possible
development of platforms for immunotherapy in solid tumors. Moreover, combining
HSCT from a related donor with solid organ transplantation could allow early
tapering of immunosuppression in recipients of solid organ transplants and
hopefully prevent organ rejection in this setting. This symposium summarizes some
of the most important recent advances in HaploSCT and provides a glimpse in the
future of fast growing field.
PMID- 29339271
TI - Early Increase in Complement Terminal Pathway Activation Marker sC5b-9 Is
Predictive for the Development of Thrombotic Microangiopathy after Stem Cell
Transplantation.
AB - Hematopoietic stem cell transplantation (HSCT)-associated thrombotic
microangiopathy (TA-TMA) is a multifactorial complication, and its prediction is
largely unresolved. Our aim was to analyze changes of complement profile after
HSCT to identify potential markers of TA-TMA development. Thirty-three
consecutive pediatric patients (9.6 +/- 4.4 years old) who underwent allogeneic
HSCT due to malignant (n = 17) or nonmalignant (n = 16) indications were included
in this study. Graft-versus-host disease (GVHD) was diagnosed using Glucksberg
criteria, viral reactivation was monitored, 5 different TA-TMA diagnostic
criteria were applied, and all important clinical and laboratory parameters of TA
TMA activity were registered. Complement pathway activities, components and
terminal pathway activation marker (sC5b-9) levels were systematically measured
before transplantation and on days 28, 56, and 100 after HSCT. During the first
100 days after HSCT, 1 of 33 patients died (day 50, multiple organ failure),
whereas 10 subjects met the criteria for TA-TMA, typically on day 61 (range, 16
to 98 days). TA-TMA was preceded by acute GVHD in 3 of 10 patients, by viral
reactivation in 2 of 10, or by both in 4 of 10 cases. Baseline sC5b-9 levels did
not differ in patients without (200 [interquartile range, 144 to 266] ng/mL), or
with (208 [interquartile range, 166 to 271] ng/mL) subsequent TA-TMA; however, on
day 28 significant differences were observed (201 [interquartile range, 185 to
290] ng/mL versus 411 [interquartile range, 337 to 471] ng/mL; P = .004).
Importantly, all 10 patients with TMA showed increase in sC5b-9 level from
baseline level to day 28, whereas in patients without TMA the same tendency was
observed for only 9 of 23 patients (P = .031). No additional complement
parameters were closely associated with the development of TA-TMA. Development of
TA-TMA occurred in 30% of our patients, typically after GVHD and/or viral
reactivation. However, early raise of sC5b-9 activation marker was predictive for
later development of TA-TMA, and should therefore be considered as an alarming
sign necessitating a careful monitoring of all TA-TMA activity markers. Further
studies enrolling a higher number of patients are necessary to determine if
terminal pathway activation is an independent predictor of TA-TMA.
PMID- 29339272
TI - An Old Friend Is Trouble for Double-Expressor and Double-Hit Lymphoma.
PMID- 29339273
TI - Electrolyte selection and microbial toxicity for electrochemical oxidative water
treatment using a boron-doped diamond anode to support site specific
contamination incident response.
AB - Intentional and unintentional contamination incidents, such as terrorist attacks,
natural disasters, and accidental spills, can result in large volumes of
contaminated water. These waters may require pre-treatment before disposal and
assurances that treated waters will not adversely impact biological processes at
wastewater treatment facilities, or receiving waters. Based on recommendations of
an industrial workgroup, this study addresses such concerns by studying
electrochemical advanced oxidation process (EAOP) pre-treatment for contaminated
waters, using a boron-doped diamond (BDD) anode, prior to discharge to wastewater
treatment facilities. Reaction conditions were investigated, and microbial
toxicity was assessed using the Microtox(r) toxicity assay and the Nitrification
Inhibition test. A range of contaminants were studied including herbicides,
pesticides, pharmaceuticals and flame retardants. Resulting toxicities varied
with supporting electrolyte from 5% to 92%, often increasing, indicating that
microbial toxicity, in addition to parent compound degradation, should be
monitored during treatment. These toxicity results are particularly novel because
they systematically compare the microbial toxicity effects of a variety of
supporting electrolytes, indicating some electrolytes may not be appropriate in
certain applications. Further, these results are the first known report of the
use of the Nitrification Inhibition test for this application. Overall, these
results systematically demonstrate that anodic oxidation using the BDD anode is
useful for addressing water contaminated with refractory organic contaminants,
while minimizing impacts to wastewater plants or receiving waters accepting EAOP
treated effluent. The results of this study indicate nitrate can be a suitable
electrolyte for incident response and, more importantly, serve as a baseline for
site specific EAOP usage.
PMID- 29339274
TI - Geochemical sources of metal contamination in a coal mining area in Chhattisgarh,
India using lead isotopic ratios.
AB - A geochemical study of the trace metals and lead isotopic ratios of soil and
sediments in Korba, Chhattisgarh, India is presented here for the first time.
Korba, the nation's 'power hub' is also the fifth among its eighty-eight most
critically polluted industrial hotspots. A very high mean concentration (in mg kg
1) of V (308), Cr (567), Mn (3442), Co (92), Cu (218), Zn (426), Pb (311), Th
(123) and U (32) characterized the sediments of the studied area with mean Igeo
values of the trace metals ranging from -2.29 to 3.27. In the two-ratio scatter
Pb isotope plot of the different environmental matrices, except for human blood,
coal, soil, sediments, non-washed leaves, flyash and diesel overlapped linearly
in the mixing line between diesel as the highest anthropogenic end member and a
core sediment fraction representing its geogenic counterpart. The mean
207Pb/206Pb Pb ratio decreased in the order of diesel (0.9012) > flyash (0.8757)
> coal (0.8498) soils and sediments (0.8374) > lowest core sediment fraction
(0.8017). Principal Component Analysis (PCA) of the trace metal data extracted V,
Cr, Cu, Zn, Pb, U and Th in the first component PC1. The northeastern part of the
study area revealed major hotspots of V, Cu, Co, Zn and Pb near the flyash dykes
of the power stations. Human blood used as a biomarker for Pb pollution in this
study had a mean blood lead level of 28 MUg/dl with a distinctive high
207Pb/206Pb ratio of 0.8828.
PMID- 29339275
TI - Biochar-based functional materials in the purification of agricultural
wastewater: Fabrication, application and future research needs.
AB - Nowadays, agricultural contamination is becoming more and more serious due to the
rapid growth of agricultural industry, which discharged antibiotics, pesticides
or toxic metals into farmlands. A large number of researchers have applied
biochar-based functional materials to the treatment of agricultural wastewater
contamination. Meanwhile, biochar has also proved to be a very promising and
effective technology in water purification field due to its various beneficial
properties (e.g., cost effective, high specific surface area, and surface
reactive groups). The focus of this review is to highlight the fabrication
methods and application of biochar-based functional materials with the removal of
different agricultural contaminants, and discuss the underlying mechanisms.
However, the application of biochar-based functional materials is currently under
its infancy, with the main hindrance is identified as the gap between laboratory
scale and field application, immaturity of engineered biochar production
technologies, and lack of quality standards. In order to fill these knowledge
gaps, more efforts should be made to pay for the relevant research in future
studies.
PMID- 29339276
TI - Reliability of oscillometric central blood pressure and central systolic loading
in individuals over 50 years: Effects of posture and fasting.
AB - BACKGROUND AND AIMS: The between-day reliability of oscillometric pulse wave
analysis has been demonstrated in a young, healthy population but not in an older
sample. This study examined the between-day reliability of the SphygmoCor XCEL in
individuals over 50 years. As blood pressure is measured in a range of postures
and fasting states (supine/seated, fasted/non-fasted), this study also
investigated the effect of these variables on central blood pressure and central
systolic loading. METHODS: Fifty-one adults (m = 21; age 57 +/- 6.4 y) were
tested on three mornings in supine and seated conditions and in fasted and non
fasted states. Data was analysed as a whole and for normotensive (n = 25) and
hypertensive participants (n = 26). RESULTS: SphygmoCor XCEL demonstrated strong
reliability in the whole sample for central systolic and diastolic blood
pressures, augmentation index (AIx) and AIx75 (ICC = 0.77-0.95). Significant
interaction effects were observed in central diastolic blood pressure, central
pulse pressure, augmentation index (AIx) and AIx75 (p < 0.05; etap2 = 0.10-0.23).
Fasting state had a greater influence on central pressures in a seated than
supine posture, but a greater effect on central systolic loading measures in a
supine posture. CONCLUSIONS: The SphygmoCor XCEL is a reliable tool to assess
central haemodynamic variables in an older population. It would be pertinent for
clinicians and researchers to record central measures in a supine posture to
minimise the effects of food consumption. Conversely, the assessment of central
systolic loading should occur in a seated condition to minimise the influence of
varying fasting states.
PMID- 29339277
TI - Molecular phylogeny of Systellognatha (Plecoptera: Arctoperlaria) inferred from
mitochondrial genome sequences.
AB - The infraorder Systellognatha is the most species-rich clade in the insect order
Plecoptera and includes six families in two superfamilies: Pteronarcyoidea
(Pteronarcyidae, Peltoperlidae, and Styloperlidae) and Perloidea (Perlidae,
Perlodidae, and Chloroperlidae). To resolve the debatable phylogeny of
Systellognatha, we carried out the first mitochondrial phylogenetic analysis
covering all the six families, including three newly sequenced mitogenomes from
two families (Perlodidae and Peltoperlidae) and 15 published mitogenomes. The
three newly reported mitogenomes share conserved mitogenomic features with other
sequenced stoneflies. For phylogenetic analyses, we assembled five datasets with
two inference methods to assess their influence on topology and nodal support
within Systellognatha. The results indicated that inclusion of the third codon
positions of PCGs, exclusion of rRNA genes, the use of nucleotide datasets and
Bayesian inference could improve the phylogenetic reconstruction of
Systellognatha. The monophyly of Perloidea was supported in the mitochondrial
phylogeny, but Pteronarcyoidea was recovered as paraphyletic and remained
controversial. In this mitochondrial phylogenetic study, the relationships within
Systellognatha were recovered as (((Perlidae + (Perlodidae + Chloroperlidae)) +
(Pteronarcyidae + Styloperlidae)) + Peltoperlidae).
PMID- 29339278
TI - Amphotericin B loaded sulfonated chitosan nanoparticles for targeting macrophages
to treat intracellular Candida glabrata infections.
AB - The current study assesses the potential of functionalised chitosan nanoparticles
(CNPs) for proficient macrophage delivery of amphotericin B (AmpB) for the
management of Candida glabrata fungemia. Chitosan was functionalised by the
method of sulfation by using chlorosulfonic acid and the developed compound was
confirmed by FTIR, 1H NMR and degree of sulfation and CHNS analysis. Amphotericin
B encapsulated sulfated chitosan (AmpB-SCNPs), when characterized showed a
hydrodynamic diameter of 310 +/- 14 nm and zeta potential of 41.5 +/- 2 mV. The
safety of AmpB-SCNPs was established by the alamar cytotoxicity assay in
nanoparticle treated macrophages following 24 h incubation. The AmpB-SCNPs showed
a significant increase in the reduction of C. glabrata in comparison with the
bare AmpB and AmpB-CNPs (55.2 and 42.7 vs 11.12 cfu/ml) indicating that AmpB
SCNPs could be a promising carrier for specific delivery of AmpB to macrophages
for effective treatment of Candida glabrata fungemia.
PMID- 29339279
TI - Green synthesis of antimicrobial and antitumor N,N,N-trimethyl chitosan
chloride/poly (acrylic acid)/silver nanocomposites.
AB - The present study is imported to solve two critical problems we face in our daily
life which are microbial pollution and colon cancer. One pot green synthesis of a
water soluble polyelectrolyte complex (PEC) between cationic polysaccharide as
N,N,N-trimethyl chitosan chloride (TMC) and anionic polymer as poly (acrylic
acid) (PAA) in presence of silver nanoparticles to yield (TMC/PAA/Ag)
nanocomposites with different Ag weight ratios. Structure of TMC, PAA and TMC/PAA
(PEC) were proved via different analysis tools. TMC/PAA and its Ag nanocomposites
are used as antimicrobial agents against different pathogenic bacteria and fungi
to solve microbial pollution. TMC/PAA-Silver nanocomposites had the highest
antimicrobial activity which increases with increasing Ag %. Cytotoxicity data
confirmed also that TMC/PAA/Ag (3%) had the most cytotoxic effect (the less cell
viability %) towards colon cancer. TMC/PAA (PEC) was formed through electrostatic
interactions between N-quaternized (-N+R3) groups in TMC and carboxylate (-COO-)
groups in PAA.
PMID- 29339280
TI - Simultaneous degumming and production of a natural gum from Crotalaria juncea
seeds: Physicochemical and rheological characterization.
AB - The oil extracted from Crotalaria juncea (Sunn-hemp) contains 70% of gum. Several
methods of degumming are attempted in order to maximize the yield of gum. During
appropriate water induced degumming, about 95-98% of phosphatides are separated.
The maximum oil yield for two types of degummimg processes are 0.59% and 0.69%
corresponding to hot water and pure O-phosphoric acid (19.88 N) treatment
respectively. The % oil yield obtained for TOP degumming is about 0.78%. Physico
chemical characteristics of the isolated gum such as moisture, ash, protein, fat
and aqueous solubility along with FTIR and TGA analysis are studied in order to
evaluate the effect of extraction process. The behaviour of gum on the molecular
scale is evaluated through alcohol treatment. Chromatographic analysis determines
the monosaccharide content of the gum with glucose: xylose: arabinose::54: 34:1.
Rheological characterization shows that the juncea gum solutions are shear rate
dependent and the behaviour is shear-thinning (or pseudoplastic). Results show
that the temperature dependent viscosity decreases with increasing shear rate.
PMID- 29339281
TI - Bifidogenic effects of Cordyceps sinensis fungal exopolysaccharide and konjac
glucomannan after ultrasound and acid degradation.
AB - The bifidogenic effects of exopolysaccharide (EPS) of a medicinal fungus
(Cordyceps sinensis) and a well-known food polysaccharide konjac glucomannan
(KGM) with different molecular weight (MW) ranges were evaluated through in vitro
experiments in liquid cultures of Bifidobacteria. Native EPS and KGM were
partially degraded with power ultrasound (US) to improve the water solubility,
and further hydrolysed with trifluoroacetic acid to much lower MW. The acid
hydrolysed fractions (EPS-AH and KGM-AH) supported the growth of all five tested
bifidobacterial species, while the US-degraded high MW fractions, EPS-US and KGM
US, could only slightly support the growth of some species. All EPS fractions
increased the acetic acid production of most bifidobacterial species. Most
remarkably, the high MW EPS-US, EPS-AH and KGM-US fractions significantly
enhanced the cell viability with much higher colony forming unit (CFU) counts,
suggesting a protective effect of these high MW polysaccharides for the bacterial
survival. The results have shown that MW was a significant factor on the
bifidogenic properties of partially degraded EPS and KGM.
PMID- 29339282
TI - Probing the interaction of two chemotherapeutic drugs of oxali-palladium and 5
fluorouracil simultaneously with milk carrier protein of beta-lactoglobulin.
AB - beta-Lactoglobulin (betaLG) is a basic element of globular carrier protein, which
is the major protein in the whey of ruminant milk and is of main interest in the
dairy industry. In the present study, the simultaneous effects of both of the
important anticancer drugs of 5-fluorouracil (5-FU) and oxali-palladium, on the
structure of betaLG were investigated using different spectroscopic methods of
fluorescence and circular dichroism (CD) in combination with a molecular docking
at two temperatures of 25 and 37 degrees C. The resulted data from intrinsic
fluorescence spectra of protein indicated that 5-FU and oxalli-palladium can
quench the fluorescence intensity of betaLG in dose-dependent manner via static
mechanism of fluorescence quenching. Analysis of fluorescence quenching data in
agreement with theoretical results have represented that there are I binding
sites on betaLG for binding of oxali-palladium and also II binding sites for 5
FU, at both temperatures of 25 and 37 degrees C. Also, competitive binding
results showed that the number of binding sites on protein for each of the drug
when the protein incubated with one of the drug did not show any changes. The
values of thermodynamic parameters of DeltaH degrees , DeltaS degrees and DeltaG
degrees illustrate that van der Waals and hydrogen-bond interactions have the
main role in the binding of oxali-palladium and 5-FU to betaLG, respectively. The
analysis of circular dichroism spectra indicated reduction in stability of the
protein and alteration in the secondary structure of protein with reduction of
alpha-helical structure and increasing of beta-sheet structure in the presence of
increasing concentration of oxali-palladium and 5-FU. Also, the transition
temperature (Tm) value of betaLG indicated the significant decreasing in the
presence of 5-FU and oxali-palladium. As a result, it can be concluded that both
of the chemotherapeutic drugs of oxali-palladium and 5-FU can bind to independent
binding sites on carrier protein of betaLG, which can be used in design and
simultaneous delivery of both drugs.
PMID- 29339283
TI - Hydroxyethyl cellulose hydrogel for wound dressing: Fabrication, characterization
and in vitro evaluation.
AB - In this study, new hydrogel membranes were developed based on hydroxyethyl
cellulose (HEC) supplemented with tungsten oxide for further implementing in
wound treatment. HEC hydrogel membranes were fabricated and crosslinked using
citric acid (CA). Various tests were carried out including FTIR, XRD, porosity
measurements, swelling, mechanical properties, gel fraction, and thermal
gravimetric analysis to evaluate the efficiency of the prepared membranes as
wound dressing material. In addition, wound healing activity of the examined
membranes for human dermal fibroblast cell line was investigated employing in
vitro scratching model. Furthermore, the potency of the prepared membranes to
suppress wound complications was studied via determination of their anti
inflammatory and antibacterial activities exploiting MTT, ELISA, and disk agar
diffusion methods. The results demonstrated that the HEC hydrogel membranes
revealed an anti-inflammatory and antibacterial efficacy. Moreover, HEC improved
the safety of tungsten oxide toward normal human cells (white blood cells and
dermal fibroblast). Furthermore, HEC membranes loaded with WO3 revealed the
highest activities against Salmonella sp. pursued by P. aeruginosa in compared
with the negative HEC hydrogel membrane. The current approach corroborated that
HEC amended by tungsten oxide could be applied as a promising safe candidate for
wound dressing material.
PMID- 29339284
TI - rBmTI-6 attenuates pathophysiological and inflammatory parameters of induced
emphysema in mice.
AB - Protease/anti-protease imbalance is the main pathogenic mechanism of emphysema
and protease inhibitors have been recognized as potential molecules to treat the
disease conditions. In this work the rBmTI-6 first domain (rBmTI-6-D1), a
recombinant Kunitz-type serine proteinase inhibitor, was used to verify its
effect in prevention or minimization of PPE-induced emphysema in mice. C57BL/6
mice were submitted to a PPE-induced emphysema model and treated with rBmTI-6-D1
before the emphysema development. We showed that the rBmTI-6-D1 treatment was
sufficient to avoid the loss of elastic recoil, an effective decrease in alveolar
enlargement and in the number of macrophages and lymphocytes in bronchoalveolar
lavage fluid. Proteolytic analysis showed a significant increase in elastase
activity in PPE-VE (induced emphysema) group that is controlled by rBmTI-6-D1.
Kallikrein activity was decreased in the PPE-rBmTI6 (induced emphysema and
inhibitor treated) group when compared to PPE-VE group. Although rBmTI-6-D1, did
not present a neutrophil elastase (NE) inhibitory activity, the results show that
the inhibitor interfered in the pathway of NE secretion in PPE-emphysema mice
model. The role of rBmTI-6-D1 in the prevention of emphysema development in the
mice model, apparently, is related with a control of inflammatory response due
the trypsin/kallikrein inhibitory activity of rBmTI-6-D1.
PMID- 29339285
TI - Facile synthesis and rheological characterization of nanocomposite hyaluronan
organoclay hydrogels.
AB - We report a facile methodology for the synthesis of inorganic-organic hydrogels
based on integrative assembly of aminopropyl magnesium phyllosilicate (aminoclay)
and sodium salt of hyaluronic acid. The viscoelastic materials produced by
electrostatic interactions and crosslinking of hyaluronan in the presence of
exfoliated synthetic organoclay results in the formation of gel-like behavior
retaining a high amount of water. This was confirmed by a rheological study
revealing significant dominance of the elastic response over the entire
deformation frequency range used. The mechanical strength of the aminoclay
hyaluronan hydrogels was found to be higher than that for related materials based
on poly(vinylpyrrolidone)-aminoclay hydrogels.
PMID- 29339286
TI - Chitosan: An undisputed bio-fabrication material for tissue engineering and bio
sensing applications.
AB - Biopolymers have been serving the mankind in various ways since long. Over the
last few years, these polymers have found great demand in various domains which
includes bio medicine, tissue engineering, bio sensor fabrications etc. because
of their excellent bio compatibility. In this context, chitosan has found global
attention due to its environmentally benign nature, biocompatibility,
biodegradability, and ease of availability. In last one decade or so, extensive
research in active biomaterials, like chitosan has led to the development of
novel delivery systems for drugs, genes, and biomolecules; and regenerative
medicine. Additionally, chitosan has also witnessed its usage in
functionalization of biocompatible materials, nanoparticle (NP) synthesis, and
immobilization of various bio-recognition elements (BREs) to form active bio
surfaces with great ease. Keeping these aspects in mind, we have written a
comprehensive review which aims to acquaint its readers with the exceptional
properties of chitosan and its usage in the domain of biomedicine, tissue
engineering, and biosensor fabrication. Herein, we have briefly explained various
aspects of direct utilization of chitosan and then presented vivid strategies
towards formulation of chitosan based nanocomposites for biomedicine, tissue
engineering, and biosensing applications.
PMID- 29339287
TI - Scalable fabrication of sulfated silk fibroin nanofibrous membranes for efficient
lipase adsorption and recovery.
AB - Fabricating adsorptive materials for fast and high efficient adsorption of
enzymes is critical to match the great demands for separation and recovery of
enzymes used as biocatalysts. However, it has proven extremely challenging. Here,
we report a cost-effective strategy to construct the sulfated group surface
functionalized silk fibroin nanofibrous membranes (SS-SFNM) under mild conditions
for positively charged Candida rugosa lipase adsorption. The naturally abundant
silk is thus reconstructed into nanofibrous membranes with tunable surface
functions. Thereby, the resultant SS-SFNM exhibited excellent adsorption
performance towards lipase, including a superior adsorption capacity of 148 mg g
1, fast adsorption equilibrium within 3 h and good reversibility. The fabrication
of such fascinating silk-based materials may provide new chance into the design
and development of multi-functional membranes for various separated applications.
PMID- 29339288
TI - Hyaluronic acid in Pluronic F-127/F-108 hydrogels for postoperative pain in
arthroplasties: Influence on physico-chemical properties and structural
requirements for sustained drug-release.
AB - In this study, we reported the hyaluronic acid (HA) on supramolecular structure
of Pluronic F-127 (PLF-127) and/or Pluronic F-108 (PLF-127) hydrogels, as well as
their effects on release mechanisms, looking forward their application as
lidocaine (LDC) drug-delivery systems in arthroplastic surgeries. We have studied
the HA-micelle interaction using Dynamic Light Scattering (DLS), the
micellization and sol-gel transition processes by Differential Scanning
Calorimetry (DSC) and Rheology., of PL-based hydrogels and. The presence of HA
provided the formation of larger micellar dimensions from ~26.0 to 42.4nm. The
incorporation of HA did not change the micellization temperatures and stabilized
hydrogels rheological properties (G'>G"), showing no interference on PL
thermoreversible properties. Small-Angle-X-ray Scattering (SAXS) patterns
revealed that HA incorporation effects were pronounced for PLF-127 and PLF-108
systems, showing transitions from lamellar to hexagonal phase organization (HA
PLF-127) and structural changes from cubic to gyroid and/or cubic to lamellar.
The HA insertion effects were also observed on drug release profiles, since lower
LDC release constants (Krel=0.24-0.41mM.h-1) were observed for HA-PLF-127, that
presented a hexagonal phase organization. Furthermore, the HA-PL systems
presented reduced in vitro cytotoxic effects, pointed out their tendency to self
assembly and possible application as drug delivery systems.
PMID- 29339289
TI - Characterization of two extracellular beta-glucosidases produced from the
cellulolytic fungus Aspergillus sp. YDJ216 and their potential applications for
the hydrolysis of flavone glycosides.
AB - A cellulolytic fungus YDJ216 was isolated from a compost and identified as an
Aspergillus sp. strain. Two extracellular beta-glucosidases, BGL1 and BGL2, were
purified using ultrafiltration, ammonium sulfate fractionation, and High-Q
chromatography. Molecular masses of BGL1 and BGL2 were estimated to be 97 and 45
kDa, respectively, by SDS-PAGE. The two enzymes eluted as one peak at 87 kDa by
Sephacryl S-200 chromatography, and located at similar positions in a zymogram
after intact gel electrophoresis, suggesting BGL1 and BGL2 might be monomeric and
dimeric, respectively. Both enzymes showed similar enzymatic properties; they
were optimally active at pH 4.0-4.5 and 60 degrees C, and had similar half-lives
at 70 degrees C. Two enzymes also preferred p-nitrophenyl glucose (pNPG) with
the same Km and hardly hydrolyzed cellobiose, suggesting both enzymes are aryl
beta-glucosidases. However, Vmax for pNPG of BGL1 (953.2 U/mg) was much higher
than those of BGL2 (66.5U/mg) and other beta-glucosidases reported. When tilianin
(a flavone glycoside of acacetin) was reacted with both enzymes, inhibitory
activity for monoamine oxidase, relating to oxidation of neurotransmitter amines,
was increased closely to the degree obtained by acacetin. These results suggest
that BGL1 and BGL2 could be used to hydrolyze flavone glycosides to improve their
inhibitory activities.
PMID- 29339290
TI - Biocatalytic strategies in the production of galacto-oligosaccharides and its
global status.
AB - Galactooligosaccharides (GOSs) are the non-digestible carbohydrates that are
composed of 3-10 or longer molecules of galactose and the terminal glucose
molecule. These are considered as prebiotics owing to their various health
benefits, and therefore is the major focus of research. These are generally
synthesized by the catalytic activity of the glycoside hydrolases (GH) utilizing
lactose as a substrate, which results in the mixture of GOSs differing in their
degree of polymerization. Different microbial glycoside hydrolases have been used
for the production. Moreover, to improve the production, different
biotechnological strategies have been applied, such as use of immobilized enzymes
or recombinant enzymes. Thus, this review discusses the different prospects of
GOSs production and its purification techniques.
PMID- 29339291
TI - Social capital and child nutrition in India: The moderating role of development.
AB - Empirical studies of social capital rarely take into account the socioeconomic
context of the region in which it operates, indeed as most of this research has
been located in high income countries. It is imperative to investigate how
development may influence the impact of social capital, especially in developing
countries. This paper examines the relationship between social capital and child
nutrition using the India Human Development Survey, 2005-2006. Using a multilevel
framework and a sample of 6770 rural children under the age of five, it finds
that household based bridging social capital, expressed as connections with
development based organizations, is positively associated with child nutrition.
Bonding social capital, expressed as ties with caste and religious based
organizations, has the opposite impact. At the village level, contextual measures
of social capital are associated with nutritional status of children, but their
influence is conditional on local development.
PMID- 29339292
TI - Selective HCN1 block as a strategy to control oxaliplatin-induced neuropathy.
AB - Chemotherapy-Induced Peripheral Neuropathy (CIPN) is the most frequent adverse
effect of pharmacological cancer treatments. The occurrence of neuropathy
prevents the administration of fully-effective drug regimen, affects negatively
the quality of life of patients, and may lead to therapy discontinuation. CIPN is
currently treated with anticonvulsants, antidepressants, opioids and non-opioid
analgesics, all of which are flawed by insufficient anti-hyperalgesic efficacy or
addictive potential. Understandably, developing new drugs targeting CIPN-specific
pathogenic mechanisms would dramatically improve efficacy and tolerability of
anti-neuropathic therapies. Neuropathies are associated to aberrant excitability
of DRG neurons due to the alteration in the expression or function of a variety
of ion channels. In this regard, Hyperpolarization-activated Cyclic Nucleotide
gated (HCN) channels are overexpressed in inflammatory and neuropathic pain
states, and HCN blockers have been shown to reduce neuronal excitability and to
ameliorate painful states in animal models. However, HCN channels are critical in
cardiac action potential, and HCN blockers used so far in pre-clinical models do
not discriminate between cardiac and non-cardiac HCN isoforms. In this work, we
show an HCN current gain of function in DRG neurons from oxaliplatin-treated
rats. Biochemically, we observed a downregulation of HCN2 expression and an
upregulation of the HCN regulatory beta-subunit MirP1. Finally, we report the
efficacy of the selective HCN1 inhibitor MEL57A in reducing hyperalgesia and
allodynia in oxaliplatin-treated rats without cardiac effects. In conclusion,
this study strengthens the evidence for a disease-specific role of HCN1 in CIPN,
and proposes HCN1-selective inhibitors as new-generation pain medications with
the desired efficacy and safety profile.
PMID- 29339293
TI - Methylphenidate significantly alters the functional coupling between the
prefrontal cortex and dopamine neurons in the ventral tegmental area.
AB - Amphetamine-like psychostimulants, including methylphenidate, have been shown to
produce two opposing effects on dopamine (DA) neurons: a DA receptor-mediated
feedback inhibition and a non-DA receptor-mediated excitation. To test whether
the latter effect is mediated through the prefrontal cortex (PFC), we made dual
site recordings from the PFC and ventral tegmental area (VTA). Consistent with
previous reports, methylphenidate inhibited VTA DA neurons. The D2 receptor
antagonist raclopride completely reversed the inhibition and further increased
the activity, particularly bursting, to above pre-drug baseline. This increase in
DA cell activity was blocked by the alpha1 receptor antagonist prazosin,
suggesting an effect mediated through alpha1 receptors. Recordings in the PFC
showed that methylphenidate increased PFC UP state duration and shifted the
functional coupling between the PFC and DA neurons from negative to positive. The
former effect was partially reversed by not only prazosin, but also raclopride,
whereas the latter was reversed only by raclopride. These results suggest that
methylphenidate increases PFC cell activity through both alpha1 and D2 receptors.
Its effect on PFC-DA cell functional coupling, however, is mediated through D2
receptors. The finding that the latter effect was unaffected by prazosin further
suggests that it does not play a significant role in the alpha1-mediated
excitatory effect of methylphenidate on DA neurons. However, the shift in PFC-DA
cell functional coupling from negative to positive may significantly alter the
relative timing between DA and glutamate release from DA and PFC terminals and
thus the synaptic plasticity that depends on DA-glutamate interaction.
PMID- 29339294
TI - Ketamine for the treatment of addiction: Evidence and potential mechanisms.
AB - Ketamine is a dissociative anaesthetic drug which acts on the central nervous
system chiefly through antagonism of the n-methyl-d-aspartate (NMDA) receptor.
Recently, ketamine has attracted attention as a rapid-acting anti-depressant but
other studies have also reported its efficacy in reducing problematic alcohol and
drug use. This review explores the preclinical and clinical research into
ketamine's ability to treat addiction. Despite methodological limitations and the
relative infancy of the field, results thus far are promising. Ketamine has been
shown to effectively prolong abstinence from alcohol and heroin in detoxified
alcoholics and heroin dependent individuals, respectively. Moreover, ketamine
reduced craving for and self-administration of cocaine in non-treatment seeking
cocaine users. However, further randomised controlled trials are urgently needed
to confirm ketamine's efficacy. Possible mechanisms by which ketamine may work
within addiction include: enhancement of neuroplasticity and neurogenesis,
disruption of relevant functional neural networks, treating depressive symptoms,
blocking reconsolidation of drug-related memories, provoking mystical experiences
and enhancing psychological therapy efficacy. Identifying the mechanisms by which
ketamine exerts its therapeutic effects in addiction, from the many possible
candidates, is crucial for advancing this treatment and may have broader
implications understanding other psychedelic therapies. In conclusion, ketamine
shows great promise as a treatment for various addictions, but well-controlled
research is urgently needed. This article is part of the Special Issue entitled
'Psychedelics: New Doors, Altered Perceptions'.
PMID- 29339295
TI - Characteristics of clinical and environmental vanM-carrying vancomycin-resistant
enterococci isolates from an infected patient.
AB - vanM, an uncommon glycopeptide resistance gene, was first identified in an
Enterococcus faecium isolate (Efm-HS0661) from Shanghai, China, in 2006 and has
been predominant in this city since 2011. A vanM-carrying E. faecium was isolated
from the bloodstream of a patient in an intensive care unit (ICU) in Hangzhou,
China, in 2014. Further surveillance screening of a rectal swab and environmental
surfaces of the patient yielded a large number of vanM-positive E. faecium. These
isolates (including 1 from the bloodstream, 1 from the rectal swab and 43
representative isolates from environmental samples) were classified into four
pulsed-field gel electrophoresis (PFGE) patterns and two sequence types (ST78 and
ST564). PCR amplification and sequence analysis indicated that the genetic
structure surrounding the vanM gene of these isolates was similar to that of the
original vanM-carrying isolate Efm-HS0661. This study highlights the emergence of
infections and environmental contamination caused by vanM-carrying E. faecium in
an ICU of another Chinese city outside of Shanghai.
PMID- 29339296
TI - Silent transmission of an IS1294b-deactivated mcr-1 gene with inducible colistin
resistance.
AB - Global dissemination of the mobile colistin resistance mcr-1 is of particular
concern as colistin is one of the last-resort antibiotics for the treatment of
severe infections caused by carbapenem-resistant Gram-negative bacteria. In this
study, an inactive form of mcr-1 in a fluoroquinolone-resistant and colistin
susceptible uropathogenic Escherichia coli isolate (ECO3347) was characterised.
The mcr-1 gene was deactivated by insertion of a 1.7-kb IS1294b element flanked
by two tetramers (GTTC) and located on a 62-kb pHNSHP45-like plasmid (p3347-mcr
1). Single-step and multistep selections were used to induce colistin resistance
in vitro in ECO3347. ECO3347 acquired colistin resistance (MIC = 16-32 mg/L) only
after a serial passage selection with increasing concentrations of colistin (2-8
mg/L). Deactivated mcr-1 was re-activated by loss of IS1294b without any remnants
in most colistin-resistant mutants. In addition, a novel amino acid variant
(Leu105Pro) in the CheY homologous receiver domain of PmrA was detected in one
colistin-resistant mutant. Plasmid p3347-mcr-1+ carrying the re-activated mcr-1
gene is transferrable to E. coli J53 recipient with a high conjugation rate (ca.
10-1 cells per recipient cell). Transconjugants showed an identical growth status
to J53, suggesting lack of a fitness cost after acquiring p3347-mcr-1+. These
results highlight that the disrupted mcr-1 gene has the potential for wide silent
dissemination with the help of pHNSHP45-like epidemic plasmids. Inducible
colistin resistance may likely compromise the success of clinical treatment and
infection control. Continuous monitoring of mcr-1 is imperative for understanding
and tackling its dissemination in different forms.
PMID- 29339297
TI - Experiences and perspectives of implementing antimicrobial stewardship in five
French hospitals: a qualitative study.
AB - The aim of this study was to describe current antimicrobial stewardship
programmes (ASPs) in France, both at policy level and at local implementation
level, and to assess how ASP leaders (ASPL) worked and prioritised their
activities. A qualitative study based on face-to-face semi-structured interviews
with healthcare professionals responsible for ASPs across five French hospitals
was conducted. Five infectious diseases specialists and one microbiologist were
interviewed between April-June 2016. Stewards had dedicated time to perform ASP
activities in two university-affiliated hospitals, whilst in the other hospitals
(one university, one general and one semi-private), ASPLs had to balance these
activities with clinical practice. Consequently, they had to adapt interventions
according to their resources (IT or human). Responding to colleagues'
consultation requests formed baseline work. Systematic and pro-active measures
allowed for provision of unsolicited counselling, whilst direct counselling on
wards required appropriate staffing. ASPLs aimed at increasing clinicians'
ability to prescribe adequately and awareness of the unintended consequences of
inappropriate use of antibiotics. Thus, persuasive, e.g. education, measures were
preferred to coercive ones. ASPLs faced several challenges in implementing the
ASP: overcoming physicians' or units' reluctance; and balancing the influence of
medical hierarchy and professional boundaries. Beyond resources constraints,
ASPLs' conceptions of their work, as well as contextual and cultural aspects, led
them to adopt a persuasive and collaborative approach of counselling. This is the
first qualitative study regarding ASPs in France exploring stewards' experiences
and points of view.
PMID- 29339298
TI - Implementation and impact of an audit and feedback antimicrobial stewardship
intervention in the orthopaedics department of a tertiary-care hospital: a
controlled interrupted time series study.
AB - A prospective audit and feedback antimicrobial stewardship intervention conducted
in the Orthopaedics Department of a university hospital in Portugal was evaluated
by comparing an interrupted time series in the intervention group with a non
intervention (control) group. Monthly antibiotic use (except cefazolin) was
measured as the World Health Organization's Anatomical Therapeutic Chemical
defined daily doses (ATC-DDD) from January 2012 to September 2016, excluding the
6-month phase of intervention implementation starting on 1 January 2015. Compared
with the control group, the intervention group had a monthly decrease in the use
of fluoroquinolones by 2.3 DDD/1000 patient-days [95% confidence interval (CI)
3.97 to -0.63]. An increase in the use of penicillins by 103.3 DDD/1000 patient
days (95% CI 47.42 to 159.10) was associated with intervention implementation,
followed by a decrease during the intervention period (slope = -5.2, 95% CI -8.56
to -1.82). In the challenging scenario of treatment of osteoarticular and
prosthetic joint infections, an audit and feedback intervention reduced
antibiotic exposure and spectrum.
PMID- 29339299
TI - Is There a Difference in the Outcome of Mid-Urethral Sling Operations Performed
by Urogynecologists Compared with Supervised Residents?
AB - STUDY OBJECTIVE: To compare the operative results of midurethral sling (MUS)
surgeries for stress urinary incontinence (SUI) performed by residents under the
guidance of an attending specialist in urogynecology and those performed by
attendings. DESIGN: Retrospective chart review (Canadian Task Force
classification II-2). SETTING: University hospital. PATIENTS: A retrospective
analysis of all MUS surgeries performed at a single public tertiary medical
center between January 2009 and December 2013 was carried out. A total of 257
patients underwent transobturator tape (TOT) placement during the study period,
including 136 (52.9%) placed by an attending specialist in urogynecology (group
A) and 121 (47.1%) placed by a resident, under the guidance of an attending
(group B). MEASUREMENTS: The efficacy of treatment was evaluated in terms of
early postoperative course, reoperation, and symptom improvement, as based on the
Pelvic Floor Distress Inventory short form (PFDI-20) questionnaire. The primary
outcome was patient-reported symptoms of SUI, as assessed with the PFDI-20
questionnaire, as well as absence of surgical retreatment for SUI. RESULTS:
Immediate postoperative complications were comparable in the 2 groups, as were
subjective failure and self-reported SUI. The primary outcome-moderate and severe
symptoms of SUI-were reported by 23.7% of the patients in group A and 23.6% of
those in group B (p = .91). At a mean follow-up of 40 months in both groups,
symptoms, as assessed using the urinary scale and prolapse scale of the PFDI-20,
were also similar in the 2 groups. The rate of reoperation with repeated sling
for SUI was 5% in both groups. CONCLUSION: The operative results of TOT surgery
for SUI performed by residents under the guidance of an attending specialist in
urogynecology did not differ significantly from those performed by the attendings
themselves.
PMID- 29339300
TI - Robotic Surgery in Elderly and Very Elderly Gynecologic Cancer Patients.
AB - STUDY OBJECTIVE: To investigate the feasibility, safety, and short-term outcomes
of robotic surgery (RS) for gynecologic oncologic indications (cervical,
endometrial, and ovarian cancer) in elderly patients, especially women age 65 to
74 years (elderly group [EG]) compared with women age >=75 years (very elderly
group [VEG]). DESIGN: Retrospective cohort study (Canadian Task Force
classification II-2). SETTING: Catholic University of the Sacred Heart, Rome,
Italy. PATIENTS: Between May 2013 and April 2017, 204 elderly and very elderly
patients underwent RS procedures for gynecologic malignancies. RESULTS: The
median age was 71 years (range, 65-74 years) in the EG and 77 years (range, 75-87
years) in the VEG. The incidence of cardiovascular disease was higher in the VEG
(p = .038). The EG and VEG were comparable in terms of operative time, blood
loss, and need for blood transfusion. Almost all (98.5%) of the patients
underwent total/radical hysterectomy, 109 patients (55.6% of the EG vs 48.3% of
the VEG) underwent pelvic lymphadenectomy, and 19 patients (10.5% of the EG vs
6.7% of the VEG) underwent aortic lymphadenectomy. A total of 7 (3.4%)
conversions to open surgery were registered. Only 3 patients required
postoperative intensive care unit admission. The median length of hospital stay
was 2 days in each group. A total of 11 patients (5.6%) had early postoperative
complications. Four patients (2.8%) in the EG and 2 patients (3.3%) in the VEG
experienced grade >=2 complications. At the time of analysis, median follow-up
was 18 months (range, 6-55 months). Eleven patients (5.6%) experienced disease
relapse, 2 (1%) died of disease, and 3 (1.5%) died of cardiovascular disease.
CONCLUSIONS: This study demonstrates the feasibility, safety, and good short-term
outcomes of RS in elderly and very elderly gynecologic cancer patients. No
patient can be considered too old for a minimally invasive robotic approach, but
a multidisciplinary approach is the best management pathway; efforts to reduce
associated morbidity are essential.
PMID- 29339301
TI - A Polypectomy Nearly Becoming a Tragedy: A Case of Multiorgan Perforation.
PMID- 29339302
TI - Bilateral Ureteral Stent Removal after 15 Years: A Case Report.
AB - We present the first reported case of a patient with a forgotten ureteral stent.
A 68-year-old woman had undergone radical hysterectomy for cervical cancer in
1997, at which time bilateral ureteral stents were placed. She was admitted to
our hospital with stranguria, dysuria, and lower back pain of 10 days duration.
Preoperative radiologic evaluation revealed the presence of ureteral stents,
which had been in place since 1997. With the patient under general anesthesia,
the bilateral stents were removed by urethral cystoscopy. No stone formation was
noted. The procedure was easy and fast, and no intraoperative complications
occurred.
PMID- 29339303
TI - Estrogenic activity of cylindrospermopsin and anatoxin-a and their oxidative
products by FeIII-B*/H2O2.
AB - The cyanotoxins released into waters during cyanobacterial blooms can pose
serious hazards to humans and animals. Apart from their toxicological mechanisms,
cyanotoxins have been shown to be involved in estrogenic activity by in vivo and
in vitro assays; however, there is limited information on the change in
estrogenicity of cyanotoxins following chemical oxidation. In this study, the
estrogenic activity of cylindrospermopsin (CYL) and anatoxin-a (ANA) at
concentrations ranging from 2.4 * 10-7 M to 2.4 * 10-12 M (CYL) and 7.1 * 10-6 M
to 7.1 * 10-11 M (ANA), and after treatment by the FeIII-B*/H2O2 catalyst system,
was investigated by the yeast estrogen screen (YES) assay. The results indicate
that CYL and ANA acted as agonists in the YES assay (CYL logEC50 = -8.901; ANA
logEC50 = -6.789), their binding affinity to estrogen receptors is associated
with their intrinsic properties, including ring structures and toxicant
properties. CYL and ANA were shown to simulate endocrine disrupting chemicals
(EDCs) to modulate the 17beta-estradiol-induced estrogenic activity, resulting in
non-monotonic dose responses. The treated CYL showed a significantly altered
estrogenicity compared to the untreated CYL (T(2) = 8.168, p <= .05), while the
estrogenicity of the treated ANA was not significantly different to the untreated
ANA (T(2) = 1.295, p > .05). Intermediate products generated from CYL and ANA
oxidized by FeIII-B*/H2O2 were identified using Q-Exactive Tandem Mass
Spectrometry (LC-MS/MS). Treatment with FeIII-B*/H2O2 yielded open-ring by
products which likely resulted in CYL's reduced binding affinity to estrogen
receptors. The insignificant change in the estrogenicity of treated ANA was
possibly a result of its multiple ring structure products, which were likely able
to bind to estrogen receptors. The comparisons for the estrogenicity of these
cyanotoxins before and after FeIII-B*/H2O2 treatment suggest that the reductions
in estrogenicity achieved by oxidation were dependent on the levels of
cyanotoxins removed, as well as the estrogenicity of the degradation products.
This is the first study on the change in the estrogenicity of CYL and ANA upon
oxidation by FeIII-B*/H2O2, a high activity catalyst system.
PMID- 29339304
TI - Transformation products formation of ciprofloxacin in UVA/LED and UVA/LED/TiO2
systems: Impact of natural organic matter characteristics.
AB - The role of natural organic matter (NOM) in contaminants removal by photolysis
and photocatalysis has aroused increasing interest. However, evaluation of the
influence of NOM characteristics on the transformation products (TPs) formation
and transformation pathways of contaminants has rarely been performed. This study
investigated the decomposition kinetics, mineralization, TPs formation and
transformation pathways of antibiotic ciprofloxacin (CIP) during photolysis and
photocatalysis in the presence of three commercial NOM isolates (Sigma-Aldrich
humic acid (SAHA), Suwannee River humic acid (SRHA) and Suwannee River NOM
(SRNOM)) by using UVA light emitting diode (UVA/LED) as an alternative light
source. NOM isolates insignificantly affected CIP photolysis but strongly
inhibited CIP photocatalysis due to competitive radical quenching. The inhibitory
effect followed the order of SAHA (49.6%) > SRHA (29.9%) > SRNOM (21.2%),
consistent with their *OH quenching abilities, SUVA254 values and orders of
aromaticity. Mineralization rates as revealed by F- release were negatively
affected by NOM during CIP photocatalysis. TPs arising from hydroxylation and
defluorination were generally suppressed by NOM isolates in UVA/LED and
UVA/LED/TiO2 systems. In contrast, dealkylation and oxidation of piperazine ring
were promoted by NOM. The enhancement in the apparent formation kinetics (kapp)
of TP245, TP291, TP334a, TP334b and TP362 followed the order of SRNOM > SRHA >
SAHA. kapp values were positively correlated with O/C ratio, carboxyl content,
E2/E3 and fluorescence index (FI) of NOM and negatively related with SUVA254
values. The observed correlations indicate that NOM properties are important in
determining the fate and transformation of organic contaminants during photolysis
and photocatalysis.
PMID- 29339305
TI - Modelling ROS formation in boreal lakes from interactions between dissolved
organic matter and absorbed solar photon flux.
AB - Concentrations of dissolved organic matter (DOM) are increasing in a large number
of lakes across the Northern hemisphere. This browning serves a dual role for
biota by protecting against harmful ultraviolet radiation, while also absorbing
photosynthetically active radiation. The photochemical activation of DOM and
subsequent formation of reactive oxygen species (ROS) is a potentially harmful
side effect, but can be difficult to measure directly in situ. In this study, we
combine a data set of physico-chemical properties from 71 Nordic lakes with in
vitro ROS formation quantum yields to predict ROS formations across a
representative boreal ecosystem gradient. For the upper centimeter of the water
column, we calculate ROS formations in the range of 7.93-12.56 MUmol L-1 h-1. In
the first meter, they range between 1.69 and 6.69 MUmol L-1 h-1 and in the
remaining depth the range is 0.01-0.46 MUmol L-1 h-1. These ROS formations are
comparable with previously field-measured hydrogen peroxide formation rates and
likely affect both phyto- and zooplankton, as well as lake chemistry.
Interestingly, wavelengths of the visible spectrum (>400 nm) contribute more than
half of the overall ROS formation in surface-near water layers. The association
between DOM and ROS formation was found to be two-fold. While DOM promotes ROS
formation in the first centimeters of the water column, the shading effect of
light attenuation overpowers this with increasing depth. In the context of water
browning, our results indicate the emergence of an underestimated oxidative
stress environment for lake biota in the upper centimeters of the water column.
PMID- 29339306
TI - Morphological changes of bacterial cells upon exposure of silver-silver chloride
nanoparticles synthesized using Agrimonia pilosa.
AB - Facile, eco-friendly synthesis of metal nanoparticles has been proposed as a cost
effective method. In the present study, we propose the facile synthesis of silver
silver chloride (Ag-AgCl) nanoparticles (NPs) using the medicinally important
Agrimonia pilosa plant extract without addition of capping or stabilizing agents.
The Ag-AgCl NPs synthesis was observed at 40 degrees C after 10 min incubation;
the synthesis of Ag-AgCl NPs was indicated by color change and confirmed by UV
vis spectroscopic peak at 454 nm. TEM analysis confirmed Ag-AgCl NPs were 10-20
nm in size and spherical, and oval in shape. Elemental composition was determined
by energy dispersive X-ray analysis, and crystalline structure was confirmed by X
ray diffraction spectroscopy. Different phytocomponents present in the plant
extract were analyzed by Gas Chromatography-Mass spectrometry, and the
interaction of biomolecules in reduction process was analyzed by Fourier
transform infrared spectroscopy studies. The synthesized Ag-AgCl NPs showed
significant antibacterial efficiency, analyzed by well diffusion assay against
pathogenic bacteria including Bacillus cereus, Listeria monocytogenes,
Staphylococcus aureus, Staphylococcus saprophyticus, Escherichia coli,
Pseudomonas putida. Minimum inhibitory concentration and minimum bactericidal
concentration were evaluated by microbroth dilution, and spread plate method,
respectively. The possible mechanism of bacterial growth inhibition is due to
changes in bacterial cell wall morphology that was studied by FE-SEM analysis.
PMID- 29339307
TI - Anticoccidial activity of fruit peel of Punica granatum L.
AB - In the interests of food safety and public health, plants and their compounds are
now re-emerging as an alternative approach to treat parasitic diseases. Here, we
studied the anticoccidial effect of different solvent extracts of the fruit peel
of Punica granatum-a commercial waste from pomegranate juice industries. The hope
underlying these experiments was to find a sustainable natural product for
controlling coccidiosis. The plant extracts were prepared using solvents of
different polarity. Acute oral toxicity study was first carried out to see the
safety of crude extracts. A high dose of crude extracts (300 mg/kg body weight)
was tested for possession of anticoccidial activity against experimentally
induced coccidial infection in broiler chicken. Activity was measured in
comparison to the reference drug amprolium on the basis of oocyst output
reduction, mean weight gain of birds and feed conversion ratio. Oocyst output was
measured using Mc-Masters counting technique. Acute oral toxicity study showed
that crude extracts of P. granatum are safe up to dosage of 2000 mg/kg body
weight. LD50 was not determined as mortalities were not recorded in any of the
five groups of chicken. For anticoccidial activity crude methanolic extract (CME)
of the fruit peel of P. granatum showed the maximum effect as evident by oocyst
output reduction (92.8 +/- 15.3), weight gain of birds (1403.0 +/- 11.9 g) and
feed conversion ratio (1.66 +/- 0.04), thereby affirming the presence of alcohol
soluble active ingredients in the plant. We also tested different doses (100-400
mg/kg body weight) of the CME of the fruit peel of P. granatum, the most active
extract on E. tenella and observed a dose dependent effect. From the present
study it can be concluded that alcoholic extract of the fruit peel of P. granatum
has significant potential to contribute to the control of coccidian parasites of
chicken.
PMID- 29339308
TI - Antibiotic resistance and virulence traits of bacterial pathogens from infected
freshwater fish, Labeo rohita.
AB - Bacterial infectious diseases are a main dangerous problem in Aquaculture
farming. It causes multiple diseases in fish as well as in human being and it has
considerable virulence potential. In this connection, the moot of study focus to
discriminate bacterial isolates recovered from naturally diseased Labeo rohita
fish and their virulent characteristics. Based on the beta-haemolysis factor,
four isolates (KADR11, KADR12, KADR13 and KADR14) were selected for further
delineation. These bacterial isolates showed high similarity with Providencia
rettgeri, Aeromonas sp., Aeromonas sp. and Aeromonas enteropelogenes
respectively, using partial 16S r-RNA gene amplification and biochemical
characterizations were also supported. The further study investigates the
virulence characteristics of isolates showed separation of outer membrane
proteins (OMPs) and lipopolysaccharides (LPS) which appeared between 19_80 kDa
and 20_100 kDa in SDS_PAGE analysis respectively. All the four strains were
complete resistant (100%) to beta-lactam antibiotics. L. rohita were injected
intraperitoneally with 0 (control), 2.0 * 104, 2.0 * 105, 2.0 * 106, 2.0 * 107
and 2.0 * 108 cells/fish of Providencia rettgeri KADR11, Aeromonas sp. KADR12,
Aeromonas sp. KADR13 and Aeromonas enteropelogenes KADR14 for the determination
of lethal dose 50 (LD50) values, which were 2.4 * 107, 4.1 * 105, 2.7 * 107 and
7.4 * 105 cells/fish respectively. The results indicated that isolated strains
were possessed the high pathogenic potential for L. rohita.
PMID- 29339309
TI - Late chronotype is associated with enhanced amygdala reactivity and reduced
fronto-limbic functional connectivity to fearful versus happy facial expressions.
AB - Increasing evidence suggests late chronotype individuals are at increased risk of
developing depression. However, the underlying neural mechanisms that confer risk
are not fully understood. Here, fifty healthy, right-handed individuals without a
current or previous diagnosis of depression, family history of depression or
sleep disorder underwent functional magnetic resonance imaging (FMRI).
Participants completed an implicit emotion processing task (gender
discrimination) including happy and fearful facial expressions. Linear effects of
chronotype on BOLD response in bilateral amygdala were tested for significance
using nonparametric permutation tests. Functional connectivity between amygdala
and prefrontal cortex was also investigated using psychophysiological interaction
(PPI) analysis. A significant negative correlation between BOLD response and
chronotype was observed in bilateral amygdala where later chronotype was
associated with an enhanced amygdala response to fearful vs. happy faces. This
response remained significant after sleep quality, age, gender, mood, and time of
scan were included as covariates in the regression model. Later chronotype was
also significantly associated with reduced functional connectivity between
amygdala and dorsal anterior cingulate cortex (dACC). The current results appear
consistent with theories of impaired emotion regulation of the limbic system
(particularly the amygdala) associated with depression and may, in part, explain
the increased vulnerability for depression in late chronotype individuals.
PMID- 29339310
TI - Distant from input: Evidence of regions within the default mode network
supporting perceptually-decoupled and conceptually-guided cognition.
AB - The default mode network supports a variety of mental operations such as semantic
processing, episodic memory retrieval, mental time travel and mind-wandering, yet
the commonalities between these functions remains unclear. One possibility is
that this system supports cognition that is independent of the immediate
environment; alternatively or additionally, it might support higher-order
conceptual representations that draw together multiple features. We tested these
accounts using a novel paradigm that separately manipulated the availability of
perceptual information to guide decision-making and the representational
complexity of this information. Using task based imaging we established regions
that respond when cognition combines both stimulus independence with multi-modal
information. These included left and right angular gyri and the left middle
temporal gyrus. Although these sites were within the default mode network, they
showed a stronger response to demanding memory judgements than to an easier
perceptual task, contrary to the view that they support automatic aspects of
cognition. In a subsequent analysis, we showed that these regions were located at
the extreme end of a macroscale gradient, which describes gradual transitions
from sensorimotor to transmodal cortex. This shift in the focus of neural
activity towards transmodal, default mode, regions might reflect a process of
where the functional distance from specific sensory enables conceptually rich and
detailed cognitive states to be generated in the absence of input.
PMID- 29339312
TI - Studying emotion theories through connectivity analysis: Evidence from
generalized psychophysiological interactions and graph theory.
AB - Psychological construction models of emotion state that emotions are variable
concepts constructed by fundamental psychological processes, whereas according to
basic emotion theory, emotions cannot be divided into more fundamental units and
each basic emotion is represented by a unique and innate neural circuitry. In a
previous study, we found evidence for the psychological construction account by
showing that several brain regions were commonly activated when perceiving
different emotions (i.e. a general emotion network). Moreover, this set of brain
regions included areas associated with core affect, conceptualization and
executive control, as predicted by psychological construction models. Here we
investigate directed functional brain connectivity in the same dataset to address
two questions: 1) is there a common pathway within the general emotion network
for the perception of different emotions and 2) if so, does this common pathway
contain information to distinguish between different emotions? We used
generalized psychophysiological interactions and information flow indices to
examine the connectivity within the general emotion network. The results revealed
a general emotion pathway that connects neural nodes involved in core affect,
conceptualization, language and executive control. Perception of different
emotions could not be accurately classified based on the connectivity patterns
from the nodes of the general emotion pathway. Successful classification was
achieved when connections outside the general emotion pathway were included. We
propose that the general emotion pathway functions as a common pathway within the
general emotion network and is involved in shared basic psychological processes
across emotions. However, additional connections within the general emotion
network are required to classify different emotions, consistent with a
constructionist account.
PMID- 29339311
TI - General, crystallized and fluid intelligence are not associated with functional
global network efficiency: A replication study with the human connectome project
1200 data set.
AB - One hallmark example of a link between global topological network properties of
complex functional brain connectivity and cognitive performance is the finding
that general intelligence may depend on the efficiency of the brain's intrinsic
functional network architecture. However, although this association has been
featured prominently over the course of the last decade, the empirical basis for
this broad association of general intelligence and global functional network
efficiency is quite limited. In the current study, we set out to replicate the
previously reported association between general intelligence and global
functional network efficiency using the large sample size and high quality data
of the Human Connectome Project, and extended the original study by testing for
separate association of crystallized and fluid intelligence with global
efficiency, characteristic path length, and global clustering coefficient. We
were unable to provide evidence for the proposed association between general
intelligence and functional brain network efficiency, as was demonstrated by van
den Heuvel et al. (2009), or for any other association with the global network
measures employed. More specifically, across multiple network definition schemes,
ranging from voxel-level networks to networks of only 100 nodes, no robust
associations and only very weak non-significant effects with a maximal R2 of 0.01
could be observed. Notably, the strongest (non-significant) effects were observed
in voxel-level networks. We discuss the possibility that the low power of
previous studies and publication bias may have led to false positive results
fostering the widely accepted notion of general intelligence being associated to
functional global network efficiency.
PMID- 29339313
TI - The human body odor compound androstadienone increases neural conflict coupled to
higher behavioral costs during an emotional Stroop task.
AB - The androgen derivative androstadienone (AND) is a substance found in human sweat
and thus may act as human chemosignal. With the current experiment, we aimed to
explore in which way AND affects interference processing during an emotional
Stroop task which used human faces as target and emotional words as distractor
stimuli. This was complemented by functional magnetic resonance imaging (fMRI) to
unravel the neural mechanism of AND-action. Based on previous accounts we
expected AND to increase neural activation in areas commonly implicated in
evaluation of emotional face processing and to change neural activation in brain
regions linked to interference processing. For this aim, a total of 80 healthy
individuals (oral contraceptive users, luteal women, men) were tested twice on
two consecutive days with an emotional Stroop task using fMRI. Our results
suggest that AND increases interference processing in brain areas that are
heavily recruited during emotional conflict. At the same time, correlation
analyses revealed that this neural interference processing was paralleled by
higher behavioral costs (response times) with higher interference related brain
activation under AND. Furthermore, AND elicited higher activation in regions
implicated in emotional face processing including right fusiform gyrus, inferior
frontal gyrus and dorsomedial cortex. In this connection, neural activation was
not coupled to behavioral outcome. Furthermore, despite previous accounts of
increased hypothalamic activation under AND, we were not able to replicate this
finding and discuss possible reasons for this discrepancy. To conclude, AND
increased interference processing in regions heavily recruited during emotional
conflict which was coupled to higher costs in resolving emotional conflicts with
stronger interference-related brain activation under AND. At the moment it
remains unclear whether these effects are due to changes in conflict detection or
resolution. However, evidence most consistently suggests that AND does not draw
attention to the most potent socio-emotional information (human faces) but rather
highlights representations of emotional words.
PMID- 29339314
TI - Surface-based characteristics of the cerebellar cortex visualized with ultra-high
field MRI.
AB - Although having a relatively homogeneous cytoarchitectonic organization, the
cerebellar cortex is a heterogeneous region characterized by different amounts of
myelin, iron and protein expression profiles. In this study, we used quantitative
T1 and T2* mapping at ultra-high field (7T) MRI to investigate the tissue
characteristics of the cerebellar gray matter surface and its layers. Detailed
subject-specific surfaces were generated at three different cortical depths and
averaged across subjects to create averaged T1- and T2*-maps on the cerebellar
surface. T1 surfaces showed an alternation of lower and higher T1 values when
going from the median to the lateral part of the cerebellar hemispheres. In
addition, longer T1 values were observed in the more superficial gray matter
layers. T2*-maps showed a similar longitudinal pattern, but no change related to
the cortical depths. These patterns are possibly due to variations in the level
of myelination, iron and zebrin protein expression.
PMID- 29339315
TI - Insulin sensitivity predicts brain network connectivity following a meal.
AB - There is converging evidence that insulin plays a role in food-reward signaling
in the brain and has effects on enhancing cognition. Little is known about how
these effects are altered in individuals with insulin resistance. The present
study was designed to identify the relationships between insulin resistance and
functional brain connectivity following a meal. Eighteen healthy adults (7 male,
11 female, age: 41-57 years-old) completed a frequently-sampled intravenous
glucose tolerance test to quantify insulin resistance. On separate days at least
one week apart, a resting state functional magnetic resonance imaging scan was
performed: once after a mixed-meal and once after a 12-h fast. Seed-based resting
state connectivity of the caudate nucleus and eigenvector centrality were used to
identify relationships between insulin resistance and functional brain
connectivity. Individuals with greater insulin resistance displayed stronger
connectivity within reward networks following a meal suggesting insulin was less
able to suppress reward. Insulin resistance was negatively associated with
eigenvector centrality in the dorsal anterior cingulate cortex following a meal.
These data suggest that individuals with less sensitivity to insulin may fail to
shift brain networks away from reward and toward cognitive control following a
meal. This altered feedback loop could promote overeating and obesity.
PMID- 29339316
TI - Diagnosis and management of neuromyelitis optica spectrum disorders - An update.
AB - Neuromyelitis optica (NMO) and Neuromyelitis optica spectrum disorders (NMOSD)
are a group of autoimmune conditions characterized by inflammatory involvement of
the optic nerve, spinal cord and central nervous system. Novel evidence showed a
key role of autoantibodies against aquaporin-4 immunoglobulin G (AQP4 IgG) in the
pathogenesis of NMOSD and, recently, new classification and diagnostic criteria
have been adopted to facilitate an earlier identification and improve the
management of these conditions. Diagnosis of NMOSD is currently based on
clinical, neuroimaging and laboratory features. Standard treatment is based on
the use of steroids and immunosuppressive drugs and aims to control the severity
of acute attacks and to prevent relapses of the disease. This review gives an
update of latest knowledge of NMOSD and NMO, emphasizing the novel diagnostic
criteria and both current and future therapeutic approaches.
PMID- 29339317
TI - Arterial stenosis in antiphospholipid syndrome: Update on the unrevealed
mechanisms of an endothelial disease.
AB - First described in 1983, antiphospholipid syndrome (APS) is an autoimmune
condition characterized by the occurrence of recurrent arterial and/or venous
thrombosis, and/or pregnancy morbidity, in the setting of persistent presence of
antiphospholipid antibodies (aPL). While thrombosis is the most well-known
pathogenic mechanism in this disorder, the relevance of some other mechanisms
such as arterial stenosis is being increasingly recognized. Arterial stenosis has
been first described in the renal arteries in patients with APS, however
intracranial and coeliac arteries can also be involved with various and treatable
clinical manifestations. The underlying pathophysiology of this stenotic arterial
vasculopathy is not fully understood but some recent studies revealed new
insights into the molecular mechanism behind this endothelial cell activation in
APS. In this review, we discuss these newly discovered mechanisms and highlight
the diagnostic and therapeutic modalities of the APS related arterial stenosis.
PMID- 29339318
TI - Dietary patterns, body mass index and inflammation: Pathways to depression and
mental health problems in adolescents.
AB - BACKGROUND: Observational studies suggest that dietary patterns may impact mental
health outcomes, although biologically plausible pathways are yet to be tested.
We aimed to elucidate the longitudinal relationship between dietary patterns,
adiposity, inflammation and mental health including depressive symptoms in a
population-based cohort of adolescents. METHODS: Data were provided from 843
adolescents participating in the Western Australian Pregnancy Cohort (Raine)
Study at 14 and 17 years (y) of age. Structural equation modelling was applied to
test our hypothesised models relating dietary patterns, energy intake and
adiposity (body mass index) at 14 y to adiposity and the pro-inflammatory
adipokine (leptin) and inflammation (high sensitivity C-reactive protein - hs
CRP) at 17 y, and these inflammatory markers to depressive symptoms (Beck
Depression Inventory) and Internalising and Externalising Behavioral Problems
(Child Behavior Check List Youth Self- Report) at 17 y. We further tested a
reverse hypothesis model, with depression at 14 y as a predictor of dietary
patterns at the same time-point. RESULTS: The tested models provided a good fit
to the data. A 'Western' dietary pattern (high intake of red meat, takeaway,
refined foods, and confectionary) at 14 y was associated with higher energy
intake and BMI at 14 y, and with BMI and biomarkers of inflammation at 17 y (all
p < .05). A 'Healthy' dietary pattern (high in fruit, vegetables, fish, whole
grains) was inversely associated with BMI and inflammation at 17 y (p < .05).
Higher BMI at 14 y was associated with higher BMI (p < .01), leptin (p < .05), hs
CRP (p < .05), depressive symptoms (p < .05) and mental health problems (p <
.05), all at 17 y. CONCLUSION: A 'Western' dietary pattern associates with an
increased risk of mental health problems including depressive symptoms in
adolescents, through biologically plausible pathways of adiposity and
inflammation, whereas a 'Healthy' dietary pattern appears protective in these
pathways. Longitudinal modelling into adulthood is indicated to confirm the
complex associations of dietary patterns, adiposity, inflammation and mental
health problems, including depressive symptoms.
PMID- 29339319
TI - Treatment with the noradrenaline re-uptake inhibitor atomoxetine alone and in
combination with the alpha2-adrenoceptor antagonist idazoxan attenuates loss of
dopamine and associated motor deficits in the LPS inflammatory rat model of
Parkinson's disease.
AB - The impact of treatment with the noradrenaline (NA) re-uptake inhibitor
atomoxetine and the alpha2-adrenoceptor (AR) antagonist idazoxan in an animal
model of Parkinson's disease (PD) was assessed. Concurrent systemic treatment
with atomoxetine and idazoxan, a combination which serves to enhance the extra
synaptic availability of NA, exerts anti-inflammatory and neuroprotective effects
following delivery of an inflammatory stimulus, the bacterial endotoxin,
lipopolysaccharide (LPS) into the substantia nigra. Lesion-induced deficits in
motor function (akinesia, forelimb-use asymmetry) and striatal dopamine (DA) loss
were rescued to varying degrees depending on the treatment. Treatment with
atomoxetine following LPS-induced lesion to the substantia nigra, yielded a
robust anti-inflammatory effect, suppressing microglial activation and expression
of the pro-inflammatory cytokine TNF-alpha whilst increasing the expression of
neurotrophic factors. Furthermore atomoxetine treatment prevented loss of
tyrosine hydroxylase (TH) positive nigral dopaminergic neurons and resulted in
functional improvements in motor behaviours. Atomoxetine alone was sufficient to
achieve most of the observed effects. In combination with idazoxan, an additional
improvement in the impairment of contralateral limb use 7 days post lesion and a
reduction in amphetamine-mediated rotational asymmetry 14 days post-lesion was
observed, compared to atomoxetine or idazoxan treatments alone. The results
indicate that increases in central NA tone has the propensity to regulate the
neuroinflammatory phenotype in vivo and may act as an endogenous neuroprotective
mechanism where inflammation contributes to the progression of DA loss. In
accordance with this, the clinical use of agents such as NA re-uptake inhibitors
and alpha2-AR antagonists may prove useful in enhancing the endogenous
neuroimmunomodulatory potential of NA in conditions associated with brain
inflammation.
PMID- 29339320
TI - Primary Obstruction of the Foramen of Luschka: Anatomy, Histology, and Clinical
Significance.
AB - BACKGROUND: The foramen of Luschka is a natural aperture between the fourth
ventricle and the subarachnoid space at the cerebellopontine angle. Membranous
closure of this foramen is referred to as primary obstruction. Available
information about this variant and its role in the development of the cysts of
the posterior fossa is contradictory. METHODS: The macroscopic and histologic
features of the obstructed foramina were examined in 61 formalin-fixed human
brains (122 foramina). Three rhomboid lips of various sizes with lateral recess
were used for comparison. Five postoperative cases of diverticulum of the foramen
of Luschka were included in this study, with 1 case presented in detail to
illustrate anatomic and histologic findings. RESULTS: Primary obstruction was
present in 11 of 122 cases. In 1 case, an enlarged rigid pouch with a thick wall
was found. The wall of the membrane in primary obstruction and the rhomboid lip
were composed of an inner ependymal, a middle glial, and an outer leptomeningeal
layer. CONCLUSIONS: The rhomboid lip is a remnant of the roof of the fourth
ventricle. Imperforation of the foramen of Luschka results in a pouch in the
cerebellopontine angle that contains choroid plexus (Bochdalek's flower basket)
and communicates with the fourth ventricle. This pouch has the potential to grow
to a diverticulum and cause clinical symptoms. Based on our clinical
observations, detailed radiologic and surgical-anatomic criteria were proposed to
support the differential diagnosis of a diverticulum of the foramen of Luschka.
Treatment strategies were also suggested.
PMID- 29339321
TI - Internal Thoracic Artery to Middle Cerebral Artery Bypass Surgery: Cadaveric
Feasibsility Study.
AB - BACKGROUND: A few options of extracranial donor vessels exist for use in
intracranial vascular bypass procedures. To our knowledge, the use of an internal
thoracic artery for cerebral revascularization has not been studied previously.
Hence, this cadaveric feasibility study was performed. METHODS: The internal
thoracic artery was dissected in 5 adult cadaveric specimens. The proximal
diameter, distal diameter, and length of the vessel were measured and recorded.
The artery was then transected distally at the seventh intercostal space and
transposed cranially, through a pterional craniotomy opening to reach the middle
cerebral artery at the skull base. RESULTS: The mean diameter of the internal
thoracic artery at its proximal end was 3.5 mm and at its distal end was 2 mm.
The average length of the vessel was 31 cm. There was no statistical difference
between the measurements recorded from different sides or sexes. In each
specimen, an internal thoracic artery was dissected, rotated superiorly, and
advanced subcutaneously behind the ear to reach the middle cerebral artery at the
skull base without difficulty and remained tensionless at the site of
anastomosis. CONCLUSIONS: In this cadaveric study, we demonstrated the
suitability of the internal thoracic artery in use as a donor vessel for a single
site anastomosis in a high-flow cerebral bypass procedure.
PMID- 29339322
TI - Endoscopic Endonasal Craniofacial Surgery for Recurrent Skull Base Meningiomas
Involving the Pterygopalatine Fossa, the Infratemporal Fossa, the Orbit, and the
Paranasal Sinus.
AB - OBJECTIVE: Skull base meningiomas carry a nonnegligible risk of recurrence. In
particular, those arising from the sphenoid wings or middle cranial fossa
penetrate into extracranial regions, uncommonly showing massive expansion into
the craniofacial regions on recurrence. The role of endoscopic endonasal surgery
for those intractable lesions remains unclear. METHODS: We performed endoscopic
endonasal craniofacial surgery for 8 recurrent meningiomas invading into the
pterygopalatine fossa, infratemporal fossa, nasopharynx, paranasal sinus, or
orbit, comprising 2 meningothelial and 1 fibrous meningiomas (World Health
Organization [WHO] grade I), 3 atypical and 1 clear cell meningiomas (grade II),
and 1 anaplastic meningioma (grade III). All were large (15-80 cm3; median, 45
cm3) and highly vascularized. RESULTS: All 8 tumors were sufficiently resected.
Gross total resection of the craniofacial part of the lesions was achieved in 5
patients (62.5%). In 3 patients with WHO grade I meningiomas and 1 with grade II,
tumors were successfully controlled as of the last follow-up. In 4 patients with
WHO grade II or III meningiomas, craniofacial lesions were controlled, whereas
original intracranial lesions were poorly controlled and became critical.
CONCLUSIONS: We consider the endoscopic endonasal approach as an acceptable, less
invasive alternative for recurrent craniofacial meningioma. Although all these
cases were relatively large and highly vascularized, preoperative endovascular
embolization of the feeding arteries contributes to significantly reducing
vascularity of the tumors, and local control of the craniofacial lesions was
successfully achieved in all cases. Endoscopic endonasal craniofacial surgery
enabled sufficient mass reduction without disfiguring facial incisions.
PMID- 29339323
TI - Mechanical Thrombectomy of Acute Middle Cerebral Artery Occlusion Using Trans
Anterior Communicating Artery Approach.
AB - BACKGROUND: A cross-circulation technique involves gaining access to a cerebral
vessel through a patent anterior or posterior communicating artery. This
technique may be used in patients with emergent large-vessel occlusions and an
unfavorable direct route to the occlusion. While few previous reports have
demonstrated a successful cross-circulation technique for treatment of emergent
large-vessel occlusions, we present the first 2 cases of transanterior
communicating artery stent retriever thrombectomy. CASE DESCRIPTION: Case #1: A
64-year-old female presented with acute right middle cerebral artery (MCA)
occlusion. She demonstrated a "triple-tandem" brachiocephalic-internal carotid
artery-middle cerebral artery occlusion, thus precluding direct access to the
right MCA. Successful stent retriever mechanical thrombectomy was performed
across the anterior communicating artery, using a left internal carotid artery
approach. Case #2: A 70-year old female presented with acute occlusion of the
left MCA and tandem occlusion of the cervical left internal carotid artery.
Multiple attempts to catheterize the left common carotid artery were
unsuccessful. She underwent successful stent retriever mechanical thrombectomy
across a patent anterior communicating artery, using a right internal carotid
artery approach. CONCLUSIONS: Timely recanalization of an occluded artery plays a
critical role in the prognosis of patients with acute ischemic stroke. Successful
stent retriever mechanical thrombectomy of an occluded MCA is possible using a
transanterior communicating artery approach in patients without a direct access
route to the occluded intracranial vessel. We review the pathophysiology of
tandem lesions, access routes to intracranial occlusions, and the literature on
cross-circulation techniques to treat emergent large-vessel occlusions.
PMID- 29339324
TI - Oscillatory Synchronous Inhibition in the Basolateral Amygdala and its Primary
Dependence on NR2A-containing NMDA Receptors.
AB - Synchronous, rhythmic firing of GABAergic interneurons is a fundamental mechanism
underlying the generation of brain oscillations, and evidence suggests that NMDA
receptors (NMDARs) play a key role in oscillatory activity by regulating the
activity of interneurons. Consistent with this, derangement of brain rhythms in
certain neuropsychiatric disorders, notably schizophrenia and autism, is
associated with NMDAR hypofunction and loss of inhibitory interneurons. In the
basolateral amygdala (BLA)-dysfunction of which is involved in a host of
neuropsychiatric diseases-, principal neurons display spontaneous, rhythmic
"bursts" of inhibitory activity, which could potentially be involved in the
orchestration of oscillations in the BLA network; here, we investigated the role
of NMDARs in these inhibitory oscillations. Rhythmic bursts of spontaneous IPSCs
(0.5 Hz average burst frequency) recorded from rat BLA principal cells were
blocked or significantly suppressed by D-AP5, and could be driven by NMDAR
activation alone. BLA interneurons generated spontaneous bursts of suprathreshold
EPSCs at a similar frequency, which were also blocked or reduced by D-AP5. PEAQX
(GluN2A-NMDAR antagonist; 0.4 MUM) or Ro-25-6981 (GluN2B-NMDAR antagonist; 5 MUM)
suppressed the IPSC and EPSC bursts; suppression by PEAQX was significantly
greater than that by Ro-25-6981. Immunohistochemical labeling revealed the
presence of both GluN2A- and GluN2B-NMDARs on GABAergic BLA interneurons, while,
functionally, GluN2A-NMDARs have the dominant role, as suggested by a greater
reduction of NMDA-evoked currents by PEAQX versus Ro-25-6981. Entrainment of BLA
principal neurons in an oscillatory generation of inhibitory activity depends
primarily on activation of GluN2A-NMDARs, and interneuronal GluN2A-NMDARs may
play a significant role.
PMID- 29339326
TI - Surround Inhibition in the Primary Motor Cortex is Task-specifically Modulated in
Non-professional Musicians but not in Healthy Controls During Real Piano Playing.
AB - Research has indicated that at the onset of a finger movement, unwanted
contractions of adjacent muscles are prevented by inhibiting the cortical areas
representing these muscles. This so-called surround inhibition (SI) seems
relevant for the performance of selective finger movements but may not be
necessary for tasks involving functional coupling between different finger
muscles. Therefore, the present study compared SI between isolated finger
movement and complex selective finger movements while playing a three-finger
sequence on the piano in nine non-professional musicians and 10 untrained control
participants. Transcranial magnetic stimulation (TMS) was applied to the
contralateral motor cortex to assess SI in the first dorsal interosseous (FDI),
abductor pollicis brevis (APB) and abductor digiti minimi (ADM) during the
movement preparation and the late phasic phases. The results reveal stronger SI
during the preparation phase than during the phasic phase (30.6% vs. 10.7%; P <
0.05) in the isolated-finger condition in both musicians and controls. Results
also show higher SI in musicians during the preparation phase of the isolated
finger condition compared to the preparation phase of the three-finger sequence
(40% vs. 15%; P < 0.05). However, the control group did not show this task
specific modulation of SI (isolated: 25% vs. sequence: 25%; P > 0.05). Thus,
musicians were able to modulate SI between conditions whereas control
participants revealed constant levels of SI. Therefore, it may be assumed that
long-term training as observed in skilled musicians is accompanied by task
specific effects on SI modulation potentially relating to the ability to perform
selective and complex finger movements.
PMID- 29339325
TI - Induction of Anti-agrin Antibodies Causes Myasthenia Gravis in Mice.
AB - Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction
(NMJ). Most cases of MG are caused by autoantibodies against the acetylcholine
receptor (AChR), muscle-specific kinase (MuSK) and low-density lipoprotein
receptor-related protein 4 (LRP4). Recent studies have identified anti-agrin
antibodies in MG patients lacking these three antibodies (i.e., triple negative
MG). Agrin is a basal lamina protein that has two isoforms. Neural agrin (N
agrin) binds to LRP4 to activate MuSK to induce AChR clusters and is thus
critical for NMJ formation. We demonstrate that mice immunized with N-agrin
showed MG-associated symptoms including muscle weakness, fragmented and distorted
NMJs. These effects were not observed in mice injected with muscle agrin (M
agrin), an isoform that is inactive in inducing AChR clusters. Treatment with
anti-N-agrin, but not anti-M-agrin, antibodies reduced agrin-induced AChR
clusters in muscle cells. Together, these observations suggest that agrin
antibodies may be play a role in MG pathogenesis.
PMID- 29339327
TI - The chaperonin CCT promotes the formation of fibrillar aggregates of gamma
tubulin.
AB - The type II chaperonin CCT is involved in the prevention of the pathogenesis of
numerous human misfolding disorders, as it sequesters misfolded proteins, blocks
their aggregation and helps them to achieve their native state. In addition, it
has been reported that CCT can prevent the toxicity of non-client amyloidogenic
proteins by the induction of non-toxic aggregates, leading to new insight in
chaperonin function as an aggregate remodeling factor. Here we add experimental
evidence to this alternative mechanism by which CCT actively promotes the
formation of conformationally different aggregates of gamma-tubulin, a non
amyloidogenic CCT client protein, which are mediated by specific CCT-gamma
tubulin interactions. The in vitro-induced aggregates were in some cases long
fiber polymers, which compete with the amorphous aggregates. Direct injection of
unfolded purified gamma-tubulin into single-cell zebra fish embryos allowed us to
relate this in vitro activity with the in vivo formation of intracellular
aggregates. Injection of a CCT-binding deficient gamma-tubulin mutant
dramatically diminished the size of the intracellular aggregates, increasing the
toxicity of the misfolded protein. These results point to CCT having a role in
the remodeling of aggregates, constituting one of its many functions in cellular
proteostasis.
PMID- 29339328
TI - Micro-morphological adaptations of the wing nodus to flight behaviour in four
dragonfly species from the family Libellulidae (Odonata: Anisoptera).
AB - Adult dragonflies can be divided into two major groups, perchers and fliers,
exhibiting notably different flight behaviour. Previous studies have yielded
conflicting results regarding the link between the wing macro-morphology and
flight style in these two groups. In this study, we present the first systematic
investigation of the micro-morphological differences of wings of percher and
flier dragonflies in four closely related species from the family Libellulidae.
Our results suggest that the shape and material composition of wing
microstructural components and, in particular, the nodus are adapted to
facilitate the specific wing functioning in fliers and perchers. The findings
further indicate a decreasing trend in the area proportion of the soft resilin
dominated cuticle in the nodus in the series of species from typical perchers to
typical fliers. Such a reduction in the resilin proportion in the nodus of fliers
is associated with an increase in the wing aspect ratio. The knot-shaped
protrusion at the nodus of perchers, which becomes notably smaller in that of
strong fliers, is likely to act as a mechanical stopper, avoiding large wing
displacements. This study aims to develop a novel framework for future research
on the relationship between wing morphology and flight behaviour in dragonflies.
PMID- 29339329
TI - Pituitary size alteration and adverse effects of radiation therapy performed in 9
dogs with pituitary-dependent hypercortisolism.
AB - The purpose of this study was to determine the therapeutic and/or adverse effects
of radiation therapy (RT) against pituitary tumors in dogs with pituitary
dependent hypercortisolism, as monitored by frequent post-RT detailed MRI
examinations, clinical signs, and changes in hormone concentrations. Nine dogs
with an adrenocorticotropic hormone (ACTH)-secreting pituitary mass diagnosed by
magnetic resonance imaging (MRI) underwent RT for 4weeks (total of 48Gy in 4-Gy
fractions). Pituitary height/brain area (P/B) value, clinical signs, basal plasma
ACTH concentrations, serum cortisol concentrations (pre- and post-ACTH
stimulation test) and adverse effects of RT were evaluated before and post-RT.
The P/B value was significantly lower in all nine dogs post-RT. One dog lacking
any neurological signs demonstrated no change in clinical signs pre and post-RT.
Out of 8 dogs which exhibited neurological signs pre-RT, half of them
demonstrated complete resolution of their signs, whereas the other half showed
transient resolution. In all animals with recurrence of neurological signs,
pituitary tumor regrowth was not observed; however, MRI revealed moderate to
severe pituitary hemorrhage. Late adverse effect (bilateral otitis media) was
observed in three of nine dogs post-RT. RT did not induce any significant changes
in the dogs' basal plasma ACTH concentration and pre- and post-ACTH serum
cortisol concentrations. In conclusion, RT is effective to reduce pituitary size
and the mass effect, but does not appear to affect blood hormone concentrations,
necessitating additional medical treatment against hypercortisolism. Periodic MRI
imaging post-RT enables early detection of adverse effects of RT.
PMID- 29339330
TI - Photocatalytic degradation of aniline using an autonomous rotating drum reactor
with both solar and UV-C artificial radiation.
AB - The aim of this work was to evaluate the performance of a novel self-autonomous
reactor technology (capable of working with solar irradiation and artificial UV
light) for water treatment using aniline as model compound. This new reactor
design overcomes the problems of the external mass transfer effect and the
accessibility to photons occurring in traditional reaction systems. The UV-light
source is located inside the rotating quartz drums (where TiO2 is immobilized),
allowing light to easily reach the water and the TiO2 surface. Several processes
(UV, H2O2, Solar, TiO2, Solar/TiO2, Solar/TiO2/H2O2 and UV/Solar/H2O2/TiO2) were
tested. The synergy between Solar/H2O2 and Solar/TiO2 processes was quantified to
be 40.3% using the pseudo-first-order degradation rate. The apparent photonic
efficiency, zeta, was also determined for evaluating light utilization. For the
Solar/TiO2/H2O2 process, the efficiency was found to be practically constant
(0.638-0.681%) when the film thickness is in the range of 1.67-3.87 MUm. However,
the efficiency increases up to 2.67% when artificial UV light was used in
combination, confirming the efficient design of this installation. Thus, if
needed, lamps can be switched on during cloudy days to improve the degradation
rate of aniline and its mineralization. Under the optimal conditions selected for
the Solar/TiO2/H2O2 process ([H2O2] = 250 mg/L; pH = 4, [TiO2] = 0.65-1.25
mg/cm2), 89.6% of aniline is degraded in 120 min. If the lamps are switched on,
aniline is completely degraded in 10 min, reaching 85% of mineralization in 120
min. TiO2 was re-used during 5 reaction cycles without apparent loss in activity
(<2%). Quantification of hydroxyl radicals and dissolved oxygen allows a chemical
based explanation of the process. Finally, the UV/Solar/TiO2/H2O2 process was
found to have lower operation costs than other systems described in literature
(0.67 ?/m3).
PMID- 29339331
TI - The catalytic destruction of antibiotic tetracycline by sulfur-doped manganese
oxide (S-MgO) nanoparticles.
AB - The present study evaluates the efficacy of S-doped MgO (S-MgO) as compared with
the plain MgO as a catalyst for destructive removal of tetracycline (TTC) in
aqueous solutions. The S-MgO had around 6% S in its structure. Doping MgO with S
caused increase in surface oxygen vacancy defects. Adding S-MgO (12 g/L) to a TTC
aqueous solution (50 mg/L) caused removal of around 99% TTC at the neutral pH
(ca. 5.1) and a short reaction time of 10 min. In comparison, plain MgO could
remove only around 15% of TTC under similar experimental conditions. Diffusing O2
into the TTC solution under the reaction with S-MgO resulted in a considerable
improvement of TTC removal as compared to diffusing N2. Complete removal of TTC
and 86.4% removal of its TOC could be obtained using 2 g/L S-MgO nanoparticles.
The removal of TTC increased with the increase in solution temperature. The
presence of nitrate, sulfate and chloride did not considerably affect the removal
of TTC using S-MgO while TTC removal significantly decreased at the presence of
bicarbonate and phosphate. The S-MgO was a stable and reusable catalyst
exhibiting much higher catalytic activity than plain MgO for the TTC destruction.
Accordingly, S-MgO is an emerging and efficient catalyst for catalytic
decomposition and mineralization of such pharmaceutical compounds as TTC under
atmospheric temperature and pressure.
PMID- 29339332
TI - Human perturbation increases the fluxes of dissolved molybdenum from land to
ocean - The case of the Jiulong River in China.
AB - Rivers contribute a substantial amount of trace metals including molybdenum (Mo)
into the oceans. The driving forces controlling the riverine fluxes of dissolved
metals still remain not fully understood. Our study then investigated the spatial
variations of dissolved metals including molybdenum in a typically human
perturbed river, the Jiulong River (JR), China. The aim of the study is to
elucidate the relevance of anthropogenic perturbation on the fluxes of dissolved
metals such as molybdenum from land to ocean. Our study shows a large spatial
variability of dissolved Mo across tributary to main stream of the JR.
Particularly, dissolved Mo was generally low (average: 5 +/- 1 nM) in the
"pristine" JR headwaters, and elevated (19 +/- 6 nM) along the lower river
continuum. Sporadically high levels of dissolved Mo occurred in the upper North
River (77 +/- 19 nM), as a result of mining activities locally. Significant
correlations of dissolved Mo with total dissolved solids (TDS) and dissolved
strontium (Sr) were observed in the whole JR (Mo = 1.4* TDS -1.7, R2 = 0.86, p <
.01; Mo = 1.2*Sr - 2.2, R2 = 0.70, p < .01, logarithmic scales). This indicates
that dissolved Mo is mobilized mainly along with other major ions such as Sr
during similar mineral dissolution processes. From the "pristine" headwaters to
the mouth of the JR, riverine Mo fluxes at the mouth of the JR has elevated by at
least 3 times due to human perturbation. Compiled historic data regarding metal
fluxes from world rivers further confirmed that small and medium rivers are
relatively more sensitive to human perturbation.
PMID- 29339333
TI - Coral reefs for coastal protection: A new methodological approach and engineering
case study in Grenada.
AB - Coastal communities in tropical environments are at increasing risk from both
environmental degradation and climate change and require urgent local adaptation
action. Evidences show coral reefs play a critical role in wave attenuation but
relatively little direct connection has been drawn between these effects and
impacts on shorelines. Reefs are rarely assessed for their coastal protection
service and thus not managed for their infrastructure benefits, while widespread
damage and degradation continues. This paper presents a systematic approach to
assess the protective role of coral reefs and to examine solutions based on the
reef's influence on wave propagation patterns. Portions of the shoreline of
Grenville Bay, Grenada, have seen acute shoreline erosion and coastal flooding.
This paper (i) analyzes the historical changes in the shoreline and the local
marine, (ii) assess the role of coral reefs in shoreline positioning through a
shoreline equilibrium model first applied to coral reef environments, and (iii)
design and begin implementation of a reef-based solution to reduce erosion and
flooding. Coastline changes in the bay over the past 6 decades are analyzed from
bathymetry and benthic surveys, historical imagery, historical wave and sea level
data and modeling of wave dynamics. The analysis shows that, at present, the
healthy and well-developed coral reefs system in the southern bay keeps the
shoreline in equilibrium and stable, whereas reef degradation in the northern bay
is linked with severe coastal erosion. A comparison of wave energy modeling for
past bathymetry indicates that degradation of the coral reefs better explains
erosion than changes in climate and historical sea level rise. Using this
knowledge on how reefs affect the hydrodynamics, a reef restoration solution is
designed and studied to ameliorate the coastal erosion and flooding. A
characteristic design provides a modular design that can meet specific
engineering, ecological and implementation criteria. Four pilot units were
implemented in 2015 and are currently being field-tested. This paper presents one
of the few existing examples available to date of a reef restoration project
designed and engineered to deliver risk reduction benefits. The case study shows
how engineering and ecology can work together in community-based adaptation. Our
findings are particularly important for Small Island States on the front lines of
climate change, who have the most to gain from protecting and managing coral
reefs as coastal infrastructure.
PMID- 29339334
TI - Eco-compensation in China: Theory, practices and suggestions for the future.
AB - Eco-compensation is the most important form of compensatory conservation in
China. However, this compensatory mechanism is criticized for vague definition
and massive government participation. For better understanding of eco
compensation in China, this paper compares theories and practices of compensatory
mechanisms in China and abroad. The analysis of theoretical backgrounds shows
that eco-compensation in China is a combination of 'ecological compensation' and
'payments for ecosystem services'. Ten compensatory projects in China and abroad
are assessed to reveal characteristics and problems of eco-compensation in China.
The results show that compensatory projects in China lagged behind mature foreign
compensatory projects in clarity of property rights, responsibility fulfillment,
executive efficiency, effectiveness, sustainability and equality. The massive
participation of the government is the major reason for the poor performance of
compensatory projects in China. However, government participation is necessary at
the present stage in China for the income gap and beneficiaries' low willingness
to pay. For the improvement of eco-compensation in China, suggestions are given
on the choice of non-market valuation methods, the creation of property rights
and the establishment of market mechanisms.
PMID- 29339335
TI - Potential impacts of offshore oil spills on polar bears in the Chukchi Sea.
AB - Sea ice decline is anticipated to increase human access to the Arctic Ocean
allowing for offshore oil and gas development in once inaccessible areas. Given
the potential negative consequences of an oil spill on marine wildlife
populations in the Arctic, it is important to understand the magnitude of impact
a large spill could have on wildlife to inform response planning efforts. In this
study we simulated oil spills that released 25,000 barrels of oil for 30 days in
autumn originating from two sites in the Chukchi Sea (one in Russia and one in
the U.S.) and tracked the distribution of oil for 76 days. We then determined the
potential impact such a spill might have on polar bears (Ursus maritimus) and
their habitat by overlapping spills with maps of polar bear habitat and movement
trajectories. Only a small proportion (1-10%) of high-value polar bear sea ice
habitat was directly affected by oil sufficient to impact bears. However, 27-38%
of polar bears in the region were potentially exposed to oil. Oil consistently
had the highest probability of reaching Wrangel and Herald islands, important
areas of denning and summer terrestrial habitat. Oil did not reach polar bears
until approximately 3 weeks after the spills. Our study found the potential for
significant impacts to polar bears under a worst case discharge scenario, but
suggests that there is a window of time where effective containment efforts could
minimize exposure to bears. Our study provides a framework for wildlife managers
and planners to assess the level of response that would be required to treat
exposed wildlife and where spill response equipment might be best stationed.
While the size of spill we simulated has a low probability of occurring, it
provides an upper limit for planners to consider when crafting response plans.
PMID- 29339336
TI - Organophosphate and brominated flame retardants in Australian indoor
environments: Levels, sources, and preliminary assessment of human exposure.
AB - Concentrations of nine organophosphate flame retardants (OPFRs) and eight
polybrominated diphenyl ethers (PBDEs) were measured in samples of indoor dust (n
= 85) and air (n = 45) from Australian houses, offices, hotels, and
transportation (buses, trains, and aircraft). All target compounds were detected
in indoor dust and air samples. Median ?9OPFRs concentrations were 40 MUg/g in
dust and 44 ng/m3 in indoor air, while median ?8PBDEs concentrations were 2.1
MUg/g and 0.049 ng/m3. Concentrations of FRs were higher in rooms that contained
carpet, air conditioners, and various electronic items. Estimated daily intakes
in adults are 14000 pg/kg body weight/day and 330 pg/kg body weight/day for
?9OPFRs and ?8PBDEs, respectively. Our results suggest that for the volatile FRs
such as tris(2-chloroethyl) phosphate (TCEP) and TCIPP, inhalation is expected to
be the more important intake pathway compared to dust ingestion and dermal
contact.
PMID- 29339337
TI - Adsorption of perfluoroalkyl substances on microplastics under environmental
conditions.
AB - Plastic debris has become an environmental problem during recent years. Among the
plastic debris, microplastics (<5 mm; MPLs) imply an extra problem due to their
capacity to enter into the fauna through ingestion. In this work, we study the
capacity of three MPLs, that include high-density polyethylene (HDPE),
polystyrene (PS) and polystyrene carboxylate (PS-COOH), to sorb 18 perfluoroalkyl
substances (PFASs; including carboxylic acids, sulphonates and one sulphonamide)
from the surrounding waters (freshwater and seawater). Conclusions drawn from the
results are that perfluoro sulphonates and sulphonamides have more tendency to be
sorbed onto MPLs. In addition, PS and PS-COOH have more affinity for PFASs than
HDPE. Finally, the increment of conductivity and pH of the water decreases the
exposure time that is necessary to reach equilibrium. However, the presence of
salts decreases the tendency of PFASs to be sorbed onto plastic surfaces. These
results highlight the problem associated with the presence of MPLs in inland and
marine waters since toxic compounds can be sorbed onto surrounding plastics that
could be ingested by aquatic fauna.
PMID- 29339338
TI - The phytotoxicities of decabromodiphenyl ether (BDE-209) to different rice
cultivars (Oryza sativa L.).
AB - Decabromodiphenyl ether (BDE-209), as a major component of brominated flame
retardants, has been detected in the agricultural soil in considerable amount.
Given that BDE-209 is toxic, ubiquitous and persistent, BDE-209 might induce
toxic effects on rice cultivars planted in contaminated soil. A comparative study
was conducted on phytotoxicities and GC-MS based antioxidant-related metabolite
levels to investigate the differences of phytotoxicities of BDE-209 to rice
cultivars in Yangtze River Delta of China. Rice seedlings were treated with BDE
209 at 0, 10, 50, 100 and 500 MUg/L in a hydroponic setup. Results showed that
BDE-209-induced phytotoxicites were cultivar-dependent and that the antioxidant
defense systems in the cultivars were disturbed differently. Among the three
selected cultivars (Jiayou 5, Lianjing 7 and Yongyou 9), Jiayou 5 and Lianjing 7
displayed lower toxic effects than Yongyou 9 in terms of the growth inhibition,
lipid peroxidation and DNA damage. The increases of antioxidant enzymes were
significantly higher in Jiayou 5 and Lianjing 7 than those in Yongyou 9.
Multivariate analysis of antioxidant-related metabolites in the three cultivars
indicated that l-tryptophan and l-valine were the most important ones among 10
metabolites responsible for the separation of cultivars. The up-regulation of l
tryptophan and l-valine were likely plant strategies to increase their tolerance.
The current results provided an insight into the development of rice cultivars
with higher BDE-209 tolerance.
PMID- 29339339
TI - Proteomics and genetic analyses reveal the effects of arsenite oxidation on
metabolic pathways and the roles of AioR in Agrobacterium tumefaciens GW4.
AB - A heterotrophic arsenite [As(III)]-oxidizing bacterium Agrobacterium tumefaciens
GW4 isolated from As(III)-rich groundwater sediment showed high As(III)
resistance and could oxidize As(III) to As(V). The As(III) oxidation could
generate energy and enhance growth, and AioR was the regulator for As(III)
oxidase. To determine the related metabolic pathways mediated by As(III)
oxidation and whether AioR regulated other cellular responses to As(III),
isobaric tags for relative and absolute quantitation (iTRAQ) was performed in
four treatments, GW4 (+AsIII)/GW4 (-AsIII), GW4-DeltaaioR (+AsIII)/GW4-DeltaaioR
(-AsIII), GW4-DeltaaioR (-AsIII)/GW4 (-AsIII) and GW4-DeltaaioR (+AsIII)/GW4
(+AsIII). A total of 41, 71, 82 and 168 differentially expressed proteins were
identified, respectively. Using electrophoretic mobility shift assay (EMSA) and
qRT-PCR, 12 genes/operons were found to interact with AioR. These results
indicate that As(III) oxidation alters several cellular processes related to
arsenite, such as As resistance (ars operon), phosphate (Pi) metabolism (pst/pho
system), TCA cycle, cell wall/membrane, amino acid metabolism and
motility/chemotaxis. In the wild type with As(III), TCA cycle flow is perturbed,
and As(III) oxidation and fermentation are the main energy resources. However,
when strain GW4-DeltaaioR lost the ability of As(III) oxidation, the TCA cycle is
the main way to generate energy. A regulatory cellular network controlled by AioR
is constructed and shows that AioR is the main regulator for As(III) oxidation,
besides, several other functions related to As(III) are regulated by AioR in
parallel.
PMID- 29339340
TI - Bioavailability and soil-to-crop transfer of heavy metals in farmland soils: A
case study in the Pearl River Delta, South China.
AB - Soil-bound heavy metals are of great concern for human health due to the
potential exposure via food chain transfer. In the present study, the occurrence,
the bioavailability and the soil-to-crop transfer of heavy metals in farmland
soils were investigated based on data from two agricultural areas, i.e. Sihui and
Shunde in South China. Six heavy metals (As, Cu, Hg, Mn, Ni and Pb) were
quantified in the farmland soils. The mean single pollution level indices (PI)
were all lower than 1 except for Hg in soils from Shunde (PI = 1.51 +/- 0.46),
suggesting the farmland soils were within clean and slightly polluted by heavy
metals. As, Cu, Ni and Pb were found to be mostly present in the non-bioavailable
form. The majority of Hg was considered potentially bioavailable, and Mn was
found to be largely bioavailable. Soil pH was an important factor influencing
bioavailability of soil-bound heavy metals. The concentrations of heavy metals in
vegetables from Sihui and Shunde were within the food hygiene standards, while
the rice grain from Sihui was polluted by Pb (PI = 10.3 +/- 23.4). Total soil
concentrations of heavy metals were not correlated to their corresponding crop
concentrations, instead, significant correlations were observed for bioavailable
concentrations in soil. The results supported the notion that the bioavailability
of the investigated heavy metals in the soil was largely responsible for their
crop uptake. The soil-to-crop transfer factors based on bioavailable
concentrations suggested that Cu, As and Hg in soils of the study area had
greater tendency to be accumulated in the vegetables than other heavy metals,
calling for further human health assessment by consuming the contaminated crops.
PMID- 29339341
TI - Health status alterations in Ruditapes philippinarum after continuous secondary
effluent exposure before and after additional tertiary treatment application.
AB - A mobile pilot plant was set up in a wastewater treatment plant (WWTP) in
southwest Spain to address potential adverse effects of effluents as a whole
contaminant, which are discharging into marine environments. Ruditapes
philippinarum specimens were exposed to different effluent concentrations (50%,
25%, 12.5%, 6.25%, and 3.15%) during seven days. After effluent exposure,
lysosomal membrane stability alterations (LMS), changes in the energy status
storage (total lipids content (TLP) and in the mitochondrial electron transport
(MET), inhibition of inflammatory mechanisms (cyclooxygenase activity (COX)), and
neurotoxic effects (acetylcholinesterase (AChE) were determined in exposed
organisms. Furthermore, potential toxic reduction in the effluent was analysed by
the application of an additional microalgae tertiary treatment called
photobiotreatment (PhtBio). Results after PhtBio confirmed the toxic effect
reduction in exposed organisms. Neuroendocrine effects, alterations in energy
budget and in lipid storage revealed alterations in clam's health status causing
stress conditions after effluent exposure.
PMID- 29339342
TI - Transgenerational impairments of reproduction and development of the marine
invertebrate Crepidula onyx resulted from long-term dietary exposure of 2,2',4,4'
tetrabromodiphenyl ether (BDE-47).
AB - Polybrominated diphenyl ethers have become ubiquitous in the environment and
elevated concentrations have often been found in marine organisms. Using the
gastropod Crepidula onyx as a study model, this multigenerational study sets out
to test the hypotheses that 1) parental dietary exposure to environmentally
realistic levels of 2,2',4,4'-tetrabrominated diphenyl ether (BDE-47) would lead
to transgenerational impairments on fitness traits of marine invertebrates, and
2) the organisms might develop adaptation/acclimation after exposure for one or
more generations. F0 generation of C. onyx was fed with the dinoflagellate
Isochrysis galbana encapsulated with two concentrations of BDE-47 (1.78 and 16.0
ng million cells-1, respectively), and half of the F1 offspring from the higher
concentration treatment was returned to control condition (transgenerational
group), while the other half received BDE-47 treatment continuously (continuous
treatment group). Bioaccumulation and maternal transfer of BDE-47 were evident in
all life stages of the F0 generation and in F1 eggs, respectively. Exposure to
BDE-47 reduced fecundity, delayed sexual maturity, and impeded embryonic
development in F0 to F2. In particular, developmental toxicity of F2 embryos was
apparent in the transgenerational group, but not in the continuous treatment
group, even when BDE-47 was not detected in the F2 embryos nor in their mothers
and they have never been exposed to the chemical. This study also suggested that
the offspring might have developed adaptation/acclimation to the exposure of BDE
47 within two generations of exposure, and that the physiological alterations
associated with acclimation/adaptation might have hindered the normal larval
development under a stress free condition. These findings highlighted the need
for long-term multigenerational studies in the ecological risk assessment of
chemicals alike.
PMID- 29339343
TI - An integrated evaluation of some faecal indicator bacteria (FIB) and chemical
markers as potential tools for monitoring sewage contamination in subtropical
estuaries.
AB - Sewage input and the relationship between chemical markers (linear alkylbenzenes
and coprostanol) and fecal indicator bacteria (FIB, Escherichia coli and
enterococci), were evaluated in order to establish thresholds values for chemical
markers in suspended particulate matter (SPM) as indicators of sewage
contamination in two subtropical estuaries in South Atlantic Brazil. Both
chemical markers presented no linear relationship with FIB due to high spatial
microbiological variability, however, microbiological water quality was related
to coprostanol values when analyzed by logistic regression, indicating that
linear models may not be the best representation of the relationship between both
classes of indicators. Logistic regression was performed with all data and
separately for two sampling seasons, using 800 and 100 MPN 100 mL-1 of E. coli
and enterococci, respectively, as the microbiological limits of sewage
contamination. Threshold values of coprostanol varied depending on the FIB and
season, ranging between 1.00 and 2.23 MUg g-1 SPM. The range of threshold values
of coprostanol for SPM are relatively higher and more variable than those
suggested in literature for sediments (0.10-0.50 MUg g-1), probably due to higher
concentration of coprostanol in SPM than in sediment. Temperature may affect the
relationship between microbiological indicators and coprostanol, since the
threshold value of coprostanol found here was similar to tropical areas, but
lower than those found during winter in temperate areas, reinforcing the idea
that threshold values should be calibrated for different climatic conditions.
PMID- 29339344
TI - Analysis and evaluation of (neuro)peptides in honey bees exposed to pesticides in
field conditions.
AB - During the last years, declines in honey bee colonies are being registered
worldwide. Cholinergic pesticides and their extensive use have been correlated to
the decline of pollinators and there is evidence that pesticides act as
neuroendocrine disruptors affecting the metabolism of neuropeptides. However,
there is a big absence of studies with quantitative results correlating the
effect of pesticide exposure with changes on neuropeptides insects, and most of
them are conducted under laboratory conditions, typically with individual active
ingredients. In this study, we present an analytical workflow to evaluate
pesticide effects on honey bees through the analysis of (neuro)peptides. The
workflow consists of a rapid extraction method and liquid chromatography with
triple quadrupole for preselected neuropeptides. For non-target analysis, high
resolution mass spectrometry, multivariate analysis and automatic identification
of discriminated peptides using a specific software and protein sequence
databases. The analytical method was applied to the analysis of target and non
target (neuro)peptides in honey bees with low and high content of a wide range of
pesticides to which have been exposed in field conditions. Our findings show that
the identification frequency of target neuropeptides decreases significantly in
honey bees with high concentration of pesticides (pesticide concentrations >= 500
MUg kg-1) in comparison with the honey bees with low content of pesticides
(pesticide concentrations <= 20 MUg kg-1). Moreover, the principal component
analysis in non-target search shows a clear distinction between peptide
concentration in honey bees with high level of pesticides and honey bees with low
level. The use of high resolution mass spectrometry has allowed the
identification of 25 non-redundant peptides responsible for discrimination
between the two groups, derived from 18 precursor proteins.
PMID- 29339345
TI - Optimizing critical source control of five priority-regulatory trace elements
from industrial wastewater in China: Implications for health management.
AB - Anthropogenic emissions of toxic trace elements (TEs) have caused worldwide
concern due to their adverse effects on human health and ecosystems. Based on a
stochastic simulation of factors' probability distribution, we established a
bottom-up model to estimate the amounts of five priority-regulatory TEs released
to aquatic environments from industrial processes in China. Total TE emissions in
China in 2010 were estimated at approximately 2.27 t of Hg, 310.09 t of As,
318.17 t of Pb, 79.72 t of Cd, and 1040.32 t of Cr. Raw chemicals, smelting, and
mining were the leading sources of TE emissions. There are apparent regional
differences in TE pollution. TE emissions are much higher in eastern and central
China than in the western provinces and are higher in the south than in the
north. This spatial distribution was characterized in detail by allocating the
emissions to 10 km * 10 km grid cells. Furthermore, the risk control for the
overall emission grid was optimized according to each cell's emission and risk
rank. The results show that to control 80% of TE emissions from major sources,
the number of top-priority control cells would be between 200 and 400, and less
than 10% of the total population would be positively affected. Based on TE risk
rankings, decreasing the population weighted risk would increase the number of
controlled cells by a factor of 0.3-0.5, but the affected population would
increase by a factor of 0.8-1.5. In this case, the adverse effects on people's
health would be reduced significantly. Finally, an optimized strategy to control
TE emissions is proposed in terms of a cost-benefit trade-off. The estimates in
this paper can be used to help establish a regional TE inventory and cyclic
simulation, and it can also play supporting roles in minimizing TE health risks
and maximizing resilience.
PMID- 29339346
TI - User-Centered Design of Learn to Quit, a Smoking Cessation Smartphone App for
People With Serious Mental Illness.
AB - BACKGROUND: Smoking rates in the United States have been reduced in the past
decades to 15% of the general population. However, up to 88% of people with
psychiatric symptoms still smoke, leading to high rates of disease and mortality.
Therefore, there is a great need to develop smoking cessation interventions that
have adequate levels of usability and can reach this population. OBJECTIVE: The
objective of this study was to report the rationale, ideation, design, user
research, and final specifications of a novel smoking cessation app for people
with serious mental illness (SMI) that will be tested in a feasibility trial.
METHODS: We used a variety of user-centered design methods and materials to
develop the tailored smoking cessation app. This included expert panel guidance,
a set of design principles and theory-based smoking cessation content,
development of personas and paper prototyping, usability testing of the app
prototype, establishment of app's core vision and design specification, and
collaboration with a software development company. RESULTS: We developed Learn to
Quit, a smoking cessation app designed and tailored to individuals with SMI that
incorporates the following: (1) evidence-based smoking cessation content from
Acceptance and Commitment Therapy and US Clinical Practice Guidelines for smoking
cessation aimed at providing skills for quitting while addressing mental health
symptoms, (2) a set of behavioral principles to increase retention and
comprehension of smoking cessation content, (3) a gamification component to
encourage and sustain app engagement during a 14-day period, (4) an app structure
and layout designed to minimize usability errors in people with SMI, and (5) a
set of stories and visuals that communicate smoking cessation concepts and skills
in simple terms. CONCLUSIONS: Despite its increasing importance, the design and
development of mHealth technology is typically underreported, hampering
scientific innovation. This report describes the systematic development of the
first smoking cessation app tailored to people with SMI, a population with very
high rates of nicotine addiction, and offers new design strategies to engage this
population. mHealth developers in smoking cessation and related fields could
benefit from a design strategy that capitalizes on the role visual engagement,
storytelling, and the systematic application of behavior analytic principles to
deliver evidence-based content.
PMID- 29339347
TI - Hospital-Owned Apps in Taiwan: Nationwide Survey.
AB - BACKGROUND: Over the last decade, the use of mobile phone apps in the health care
industry has grown rapidly. Owing to the high penetration rate of Internet use in
Taiwan, hospitals are eager to provide their own apps to improve the
accessibility of medical care for patients. OBJECTIVE: The aims of this study
were to provide an overview of the currently available hospital-owned apps in
Taiwan and to conduct a cross-hospital comparison of app features. METHODS: In
May 2017, the availability of apps from all 414 hospitals in Taiwan was surveyed
from the hospital home pages and the Google Play app store. The features of the
downloaded apps were then examined in detail and, for each app, the release date
of the last update, download frequency, and rating score were obtained from
Google Play. RESULTS: Among all the 414 hospitals in Taiwan, 150 (36.2%) owned
Android apps that had been made available for public use, including 95% (18/19)
of the academic medical centers, 77% (63/82) of the regional hospitals, and 22.0%
(69/313) of the local community hospitals. Among the 13 different functionalities
made available by the various hospital-owned apps, the most common were the
doctor search (100%, 150/150), real-time queue monitoring (100%, 150/150), and
online appointment scheduling (94.7%, 142/150) functionalities. The majority of
apps (57.3%, 86/150) had a rating greater than 4 out of 5, 49.3% (74/150) had
been updated at some point in 2017, and 36.0% (54/150) had been downloaded 10,000
to 50,000 times. CONCLUSIONS: More than one-third of the hospitals owned apps
intended to increase patient access to health care. The most common app features
might reflect the health care situation in Taiwan, where the overcrowded
outpatient departments of hospitals operate in an open-access mode without any
strict referral system. Further research should focus on the effectiveness and
safety of these apps.
PMID- 29339349
TI - Jeremy Hunt's new department: major overhaul or window dressing?
PMID- 29339348
TI - Evaluation Criteria of Noninvasive Telemonitoring for Patients With Heart
Failure: Systematic Review.
AB - BACKGROUND: Telemonitoring can improve heart failure (HF) management, but there
is no standardized evaluation framework to comprehensively evaluate its impact.
OBJECTIVE: Our objectives were to list the criteria used in published evaluations
of noninvasive HF telemonitoring projects, describe how they are used in the
evaluation studies, and organize them into a consistent scheme. METHODS: Articles
published from January 1990 to August 2015 were obtained through MEDLINE, Web of
Science, and EMBASE. Articles were eligible if they were original reports of a
noninvasive HF telemonitoring evaluation study in the English language. Studies
of implantable telemonitoring devices were excluded. Each selected article was
screened to extract the description of the telemonitoring project and the
evaluation process and criteria. A qualitative synthesis was performed. RESULTS:
We identified and reviewed 128 articles leading to 52 evaluation criteria
classified into 6 dimensions: clinical, economic, user perspective, educational,
organizational, and technical. The clinical and economic impacts were evaluated
in more than 70% of studies, whereas the educational, organizational, and
technical impacts were studied in fewer than 15%. User perspective was the most
frequently covered dimension in the development phase of telemonitoring projects,
whereas clinical and economic impacts were the focus of later phases.
CONCLUSIONS: Telemonitoring evaluation frameworks should cover all 6 dimensions
appropriately distributed along the telemonitoring project lifecycle. Our next
goal is to build such a comprehensive evaluation framework for telemonitoring and
test it on an ongoing noninvasive HF telemonitoring project.
PMID- 29339350
TI - Correction: The constant threat from a non-native predator increases tail muscle
and fast-start swimming performance in Xenopus tadpoles.
PMID- 29339351
TI - High-Target Versus Low-Target Blood Pressure Management During Cardiopulmonary
Bypass to Prevent Cerebral Injury in Cardiac Surgery Patients: A Randomized
Controlled Trial.
AB - BACKGROUND: Cerebral injury is an important complication after cardiac surgery
with the use of cardiopulmonary bypass. The rate of overt stroke after cardiac
surgery is 1% to 2%, whereas silent strokes, detected by diffusion-weighted
magnetic resonance imaging, are found in up to 50% of patients. It is unclear
whether a higher versus a lower blood pressure during cardiopulmonary bypass
reduces cerebral infarction in these patients. METHODS: In a patient- and
assessor-blinded randomized trial, we allocated patients to a higher (70-80 mm
Hg) or lower (40-50 mm Hg) target for mean arterial pressure by the titration of
norepinephrine during cardiopulmonary bypass. Pump flow was fixed at 2.4 L.min
1.m-2. The primary outcome was the total volume of new ischemic cerebral lesions
(summed in millimeters cubed), expressed as the difference between diffusion
weighted imaging conducted preoperatively and again postoperatively between days
3 and 6. Secondary outcomes included diffusion-weighted imaging-evaluated total
number of new ischemic lesions. RESULTS: Among the 197 enrolled patients, mean
(SD) age was 65.0 (10.7) years in the low-target group (n=99) and 69.4 (8.9)
years in the high-target group (n=98). Procedural risk scores were comparable
between groups. Overall, diffusion-weighted imaging revealed new cerebral lesions
in 52.8% of patients in the low-target group versus 55.7% in the high-target
group (P=0.76). The primary outcome of volume of new cerebral lesions was
comparable between groups, 25 mm3 (interquartile range, 0-118 mm3; range, 0-25
261 mm3) in the low-target group versus 29 mm3 (interquartile range, 0-143 mm3;
range, 0-22 116 mm3) in the high-target group (median difference estimate, 0; 95%
confidence interval, -25 to 0.028; P=0.99), as was the secondary outcome of
number of new lesions (1 [interquartile range, 0-2; range, 0-24] versus 1
[interquartile range, 0-2; range, 0-29] respectively; median difference estimate,
0; 95% confidence interval, 0-0; P=0.71). No significant difference was observed
in frequency of severe adverse events. CONCLUSIONS: Among patients undergoing on
pump cardiac surgery, targeting a higher versus a lower mean arterial pressure
during cardiopulmonary bypass did not seem to affect the volume or number of new
cerebral infarcts. CLINICAL TRIAL REGISTRATION: URL:
https://www.clinicaltrials.gov. Unique identifier: NCT02185885.
PMID- 29339353
TI - Correction: Prevention of Colitis and Colitis-Associated Colorectal Cancer by a
Novel Polypharmacological Histone Deacetylase Inhibitor.
PMID- 29339354
TI - Correction: Phase Ib/II Study of the Safety and Efficacy of Combination Therapy
with Multikinase VEGF Inhibitor Pazopanib and MEK Inhibitor Trametinib In
Advanced Soft Tissue Sarcoma.
PMID- 29339355
TI - Re-Evaluation of the Normal Range of Serum Total CO2 Concentration.
AB - A reliable determination of blood pH, PCO2, and [HCO3-] is necessary for
assessing the acid-base status of a patient. However, most acid-base disorders
are first recognized through abnormalities in serum total CO2 concentration
([TCO2]) in venous blood, a surrogate for [HCO3-]. In screening patients on the
basis of serum [TCO2], we have been concerned about the wide limits of normal for
serum [TCO2], 10-13 mEq/L, reported by many clinical laboratories. Indeed, we
have encountered patients with serum [TCO2] values within the lower or upper end
of the normal range of the reporting laboratory, who subsequently were shown to
have a cardinal acid-base disorder.Here, we present a patient who had a serum
[TCO2] within the lower end of the normal range of the clinical laboratory, which
resulted in delayed diagnosis of a clinically important "hidden" acid-base
disorder. To better define the appropriate limits of normal for serum [TCO2], we
derived the expected normal range in peripheral venous blood in adults at sea
level from carefully conducted acid-base studies. We then compared this range, 23
to 30 mEq/L, to that reported by 64 clinical laboratories, 2 large commercial
clinical laboratories, and the major textbook of clinical chemistry. For the most
part, the range in the laboratories we queried was substantially different than
that we derived and that published in the textbook, with some laboratories
reporting values as low as 18-20 mEq/L and as high as 33-35 mEq/L. We conclude
that the limits of values of serum [TCO2] reported by clinical laboratories are
very often inordinately wide and not consistent with the range of normal expected
in healthy individuals at sea level. We suggest that the limits of normal of
serum [TCO2] at sea level be tightened to 23-30 mEq/L. Such correction will
ensure recognition of the majority of "hidden" acid-base disorders.
PMID- 29339356
TI - Kidney Biomarkers and Decline in eGFR in Patients with Type 2 Diabetes.
AB - BACKGROUND AND OBJECTIVES: Biomarkers may improve identification of individuals
at risk of eGFR decline who may benefit from intervention or dialysis planning.
However, available biomarkers remain incompletely validated for risk
stratification and prediction modeling. DESIGN, SETTING, PARTICIPANTS, &
MEASUREMENTS: We examined serum cystatin C, urinary kidney injury molecule-1
(uKIM-1), and urinary neutrophil gelatinase-associated lipocalin (UNGAL) in 5367
individuals with type 2 diabetes mellitus and recent acute coronary syndromes
enrolled in the Examination of Cardiovascular Outcomes with Alogliptin versus
Standard of Care (EXAMINE) trial. Baseline concentrations and 6-month changes in
biomarkers were also evaluated. Cox proportional regression was used to assess
associations with a 50% decrease in eGFR, stage 5 CKD (eGFR<15 ml/min per 1.73
m2), or dialysis. RESULTS: eGFR decline occurred in 98 patients (1.8%) over a
median of 1.5 years. All biomarkers individually were associated with higher risk
of eGFR decline (P<0.001). However, when adjusting for baseline eGFR,
proteinuria, and clinical factors, only baseline cystatin C (adjusted hazard
ratio per 1 SD change, 1.66; 95% confidence interval, 1.41 to 1.96; P<0.001) and
6-month change in urinary neutrophil gelatinase-associated lipocalin (adjusted
hazard ratio per 1 SD change, 1.07; 95% confidence interval, 1.02 to 1.12;
P=0.004) independently associated with CKD progression. A base model for
predicting kidney function decline with nine standard risk factors had strong
discriminative ability (C-statistic 0.93). The addition of baseline cystatin C
improved discrimination (C-statistic 0.94), but it failed to reclassify risk
categories of individuals with and without eGFR decline. CONCLUSIONS: The
addition of cystatin C or biomarkers of tubular injury did not meaningfully
improve the prediction of eGFR decline beyond common clinical factors and routine
laboratory data in a large cohort of patients with type 2 diabetes and recent
acute coronary syndrome. PODCAST: This article contains a podcast at
https://www.asn
online.org/media/podcast/CJASN/2018_01_16_CJASNPodcast_18_3_G.mp3.
PMID- 29339357
TI - Family History and Risk of Second Primary Breast Cancer after In Situ Breast
Carcinoma.
AB - Background: Incidence rates of in situ breast carcinomas have increased due to
widespread adoption of mammography. Very little is known about why some women
with in situ breast cancer later develop second primary breast cancers.Methods:
In this population-based nested case-control study among in situ breast cancer
survivors, including 539 cases with a second primary breast cancer and 994
matched controls, we evaluated the association between first-degree family
history of breast cancer and risk of developing a second primary breast
cancer.Results: First-degree family history of breast cancer was associated with
an increased risk of developing a second primary breast cancer among women with a
previous in situ breast cancer [odds ratio (OR) = 1.33, 95% confidence interval
(CI), 1.05-1.69] and those with two or more affected first-degree relatives had
an even higher risk (OR = 1.94; 95% CI, 1.15-3.28). Those whose relative was
diagnosed at less than 50 years old were more likely to develop a second primary
breast cancer (OR = 1.78; 95% CI, 1.24-2.57). No difference in risks associated
with number or age of affected relatives was observed by menopausal
status.Conclusions: Results from this study suggest that first-degree family
history of breast cancer may be an important risk factor for development of a
second primary breast cancer among women with a previous in situ breast
cancer.Impact: Given the growing population of in situ breast cancer survivors, a
better understanding of risk factors associated with development of a second
primary breast cancer is needed to further understand risk. Cancer Epidemiol
Biomarkers Prev; 27(3); 315-20. (c)2018 AACR.
PMID- 29339360
TI - First Comprehensive Companion Diagnostic OK'd.
AB - The FDA has approved F1CDx, a comprehensive companion diagnostic test that can
detect genetic alterations and two genomic signatures in any type of solid tumor.
Patients with five common types of advanced cancer can be matched to one of 17
targeted therapies with this single test.
PMID- 29339358
TI - Family History of Cancer and Risk of Biliary Tract Cancers: Results from the
Biliary Tract Cancers Pooling Project.
AB - Background: Although some familial cancer syndromes include biliary tract cancers
(BTCs; cancers of the gallbladder, intrahepatic and extrahepatic bile ducts, and
ampulla of Vater), the few studies that have examined the relationships between
family history of cancer (FHC) and BTCs have reported inconclusive findings. The
objective of this study was to investigate the associations of FHC with risk of
BTC in the Biliary Tract Cancers Pooling Project (BiTCaPP).Methods: We used Cox
proportional hazards regressions models to estimate HRs and 95% confidence
intervals for associations between FHC (any, first-degree, in female relative, in
male relative, relative with gastrointestinal cancer, and relative with
hormonally related cancer) and BTC risk by anatomic site within the biliary
tract, adjusting for sex and race/ethnicity. Sensitivity analyses were conducted
that restricted to studies reporting cholecystectomy data and to people without a
history of cholecystectomy.Results: Data on FHC were available from 12
prospective studies within BiTCaPP, which collectively contributed 2,246 cases
(729 gallbladder, 345 intrahepatic and 615 extrahepatic bile duct, and 385
ampulla of Vater cancers) with 21,706,107 person-years of follow-up. A marginal,
inverse association between FHC and gallbladder cancer was driven to the null
when analysis was restricted to studies reporting cholecystectomy data and to
people without a history of cholecystectomy. FHC was not associated with risk of
BTC at the other anatomic sites.Conclusions: These findings do not support an
association between FHC and BTCs.Impact: In a study of 1.5 million people, FHC is
not a risk factor for BTCs. Cancer Epidemiol Biomarkers Prev; 27(3); 348-51.
(c)2018 AACR.
PMID- 29339361
TI - David Oliver: Will we now see a serious attempt to tackle social care funding?
PMID- 29339359
TI - Genetic Variants in Immune-Related Pathways and Breast Cancer Risk in African
American Women in the AMBER Consortium.
AB - Background: Constitutional immunity shaped by exposure to endemic infectious
diseases and parasitic worms in Sub-Saharan Africa may play a role in the
etiology of breast cancer among African American (AA) women.Methods: A total of
149,514 gene variants in 433 genes across 45 immune pathways were analyzed in the
AMBER consortium among 3,663 breast cancer cases and 4,687 controls. Gene-based
pathway analyses were conducted using the adaptive rank truncated product
statistic for overall breast cancer risk, and risk by estrogen receptor (ER)
status. Unconditional logistic regression analysis was used to estimate ORs and
95% confidence intervals (CIs) for single variants.Results: The top pathways were
Interleukin binding (P = 0.01), Biocarta TNFR2 (P = 0.005), and positive
regulation of cytokine production (P = 0.024) for overall, ER+, and ER- cancers,
respectively. The most significant gene was IL2RB (P = 0.001) for overall cancer,
with rs228952 being the top variant identified (OR = 0.85; 95% CI, 0.79-0.92).
Only BCL3 contained a significant variant for ER+ breast cancer. Variants in
IL2RB, TLR6, IL8, PRKDC, and MAP3K1 were associated with ER- disease. The only
genes showing heterogeneity between ER- and ER+ cancers were TRAF1, MAP3K1, and
MAPK3 (P <= 0.02). We also noted genes associated with autoimmune and atopic
disorders.Conclusions: Findings from this study suggest that genetic variants in
immune pathways are relevant to breast cancer susceptibility among AA women, both
for ER+ and ER- breast cancers.Impact: Results from this study extend our
understanding of how inherited genetic variation in immune pathways is relevant
to breast cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 27(3); 321-30.
(c)2018 AACR.
PMID- 29339362
TI - Circulation: Arrhythmia and Electrophysiology Editors and Editorial Board.
PMID- 29339363
TI - In This Issue: January.
PMID- 29339365
TI - Under pressure: meeting demand safely means knowing when to shout for help.
PMID- 29339364
TI - Wider effects of the Bawa-Garba case on medical practice and public safety.
PMID- 29339366
TI - Healthcare in Trump's first year.
PMID- 29339368
TI - GMC's push for erasure of paediatrician is questionable.
PMID- 29339370
TI - Nature's Wastebasket: The Role of the External Carotid Artery in Acute Stroke.
AB - We describe a novel technical approach to acute stroke illustrated by the case of
a 41 year old male who presented with tandem right common carotid artery (CCA)
and M1 occlusions. His NIHSS was 17 and Alberta stroke programe early CT score
(ASPECTs) was 8. Thrombectomy initially proved challenging due to large volume
CCA thrombus that repeatedly occluded the aspiration catheters. However, by
inflating a balloon distally and pulling clot into the adjacent ECA, we were able
to quickly restore distal contrast flow to the intracranial circulation and
achieve Thrombolysis In Cerebral Infarction/Arterial Occlusive Lesion
(TICI2C/AOL3) revascularization.
PMID- 29339372
TI - Correction: Mismatch Repair Proteins Initiate Epigenetic Alterations during
Inflammation-Driven Tumorigenesis.
PMID- 29339373
TI - A year in health and healthcare under President Trump.
PMID- 29339374
TI - Multicenter evaluation of a new closed system drug-transfer device in reducing
surface contamination by antineoplastic hazardous drugs.
AB - PURPOSE: Results of a study to evaluate the effectiveness of a recently
introduced closed system drug-transfer device (CSTD) in reducing surface
contamination during compounding and simulated administration of antineoplastic
hazardous drugs (AHDs) are reported. METHODS: Wipe samples were collected from 6
predetermined surfaces in compounding and infusion areas of 13 U.S. cancer
centers to establish preexisting levels of surface contamination by 2 marker AHDs
(cyclophosphamide and fluorouracil). Stainless steel templates were placed over
the 6 previously sampled surfaces, and the marker drugs were compounded and
infused per a specific protocol using all components of the CSTD. Wipe samples
were collected from the templates after completion of tasks and analyzed for both
marker AHDs. RESULTS: Aggregated results of wipe sampling to detect preexisting
contamination at the 13 study sites showed that overall, 66.7% of samples (104 of
156) had detectable levels of at least 1 marker AHD; subsequent testing after
CSTD use per protocol found a sample contamination rate of 5.8% (9 of 156
samples). In the administration areas alone, the rate of preexisting
contamination was 78% (61 of 78 samples); with use of the CSTD protocol, the
contamination rate was 2.6%. Twenty-six participants rated the CSTD for ease of
use, with 100% indicating that they were satisfied or extremely satisfied.
CONCLUSION: A study involving a rigorous protocol and 13 cancer centers across
the United States demonstrated that the CSTD reduced surface contamination by
cyclophosphamide and fluorouracil during compounding and simulated
administration. Participants reported that the CSTD was easy to use.
PMID- 29339375
TI - TUSC2 Immunogene Therapy Synergizes with Anti-PD-1 through Enhanced Proliferation
and Infiltration of Natural Killer Cells in Syngeneic Kras-Mutant Mouse Lung
Cancer Models.
AB - Expression of the multikinase inhibitor encoded by the tumor suppressor gene
TUSC2 (also known as FUS1) is lost or decreased in non-small cell lung carcinoma
(NSCLC). TUSC2 delivered systemically by nanovesicles has mediated tumor
regression in clinical trials. Because of the role of TUSC2 in regulating immune
cells, we assessed TUSC2 efficacy on antitumor immune responses alone and in
combination with anti-PD-1 in two Kras-mutant syngeneic mouse lung cancer models.
TUSC2 alone significantly reduced tumor growth and prolonged survival compared
with anti-PD-1. When combined, this effect was significantly enhanced, and
correlated with a pronounced increases in circulating and splenic natural killer
(NK) cells and CD8+ T cells, and a decrease in regulatory T cells (Tregs),
myeloid-derived suppressor cells (MDSCs), and T-cell checkpoint receptors PD-1,
CTLA-4, and TIM-3. TUSC2 combined with anti-PD-1 induced tumor infiltrating more
than NK and CD8+ T cells and fewer MDSCs and Tregs than each agent alone, both in
subcutaneous tumor and in lung metastases. NK-cell depletion abrogated the
antitumor effect and Th1-mediated immune response of this combination, indicating
that NK cells mediate TUSC2/anti-PD-1 synergy. Release of IL15 and IL18 cytokines
and expression of the IL15Ralpha chain and IL18R1 were associated with NK-cell
activation by TUSC2. Immune response-related gene expression in the tumor
microenvironment was altered by combination treatment. These data provide a
rationale for immunogene therapy combined with immune checkpoint blockade in the
treatment of NSCLC. Cancer Immunol Res; 6(2); 163-77. (c)2018 AACR.
PMID- 29339376
TI - Tumor Immunity and Survival as a Function of Alternative Neopeptides in Human
Cancer.
AB - The immune system exerts antitumor activity via T cell-dependent recognition of
tumor-specific antigens. Although the number of tumor neopeptides-peptides
derived from somatic mutations-often correlates with immune activity and
survival, most classically defined high-affinity neopeptides (CDNs) are not
immunogenic, and only rare CDNs have been linked to tumor rejection. Thus, the
rules of tumor antigen recognition remain incompletely understood. Here, we
analyzed neopeptides, immune activity, and clinical outcome from 6,324 patients
across 27 tumor types. We characterized a class of "alternatively defined
neopeptides" (ADNs), which are mutant peptides predicted to bind MHC (class I or
II) with improved affinity relative to their nonmutated counterpart. ADNs are
abundant and molecularly distinct from CDNs. The load of ADNs correlated with
intratumoral T-cell responses and immune suppression, and ADNs were also strong
predictors of patient survival across tumor types. These results expand the
spectrum of mutation-derived tumor antigens with potential clinical relevance.
Cancer Immunol Res; 6(3); 1-12. (c)2018 AACR.
PMID- 29339378
TI - Smartphone GP consultation app cost CCG L150 000 in first two months.
PMID- 29339379
TI - Correction: Lipid signaling to membrane proteins: From second messengers to
membrane domains and adapter-free endocytosis.
PMID- 29339377
TI - Robust Antitumor Responses Result from Local Chemotherapy and CTLA-4 Blockade.
AB - Clinical responses to immunotherapy have been associated with augmentation of
preexisting immune responses, manifested by heightened inflammation in the tumor
microenvironment. However, many tumors have a noninflamed microenvironment, and
response rates to immunotherapy in melanoma have been <50%. We approached this
problem by utilizing immunotherapy (CTLA-4 blockade) combined with chemotherapy
to induce local inflammation. In murine models of melanoma and prostate cancer,
the combination of chemotherapy and CTLA-4 blockade induced a shift in the
cellular composition of the tumor microenvironment, with infiltrating CD8+ and
CD4+ T cells increasing the CD8/Foxp3 T-cell ratio. These changes were associated
with improved survival of the mice. To translate these findings into a clinical
setting, 26 patients with advanced melanoma were treated locally by isolated limb
infusion with the nitrogen mustard alkylating agent melphalan followed by
systemic administration of CTLA-4 blocking antibody (ipilimumab) in a phase II
trial. This combination of local chemotherapy with systemic checkpoint blockade
inhibitor resulted in a response rate of 85% at 3 months (62% complete and 23%
partial response rate) and a 58% progression-free survival at 1 year. The
clinical response was associated with increased T-cell infiltration, similar to
that seen in the murine models. Together, our findings suggest that local
chemotherapy combined with checkpoint blockade-based immunotherapy results in a
durable response to cancer therapy. Cancer Immunol Res; 6(2); 189-200. (c)2018
AACR.
PMID- 29339381
TI - Cholecystokinin is involved in triglyceride fatty acid uptake by rat adipose
tissue.
AB - The incorporation of plasma triglyceride (TG) fatty acids to white adipose tissue
(WAT) depends on lipoprotein lipase (LPL), which is regulated by angiopoietin
like protein-4 (ANGPTL-4), an unfolding molecular chaperone that converts active
LPL dimers into inactive monomers. The production of ANGPTL-4 is promoted by
fasting and repressed by feeding. We hypothesized that the postprandial hormone
cholecystokinin (CCK) facilitates the storage of dietary TG fatty acids in WAT by
regulating the activity of the LPL/ANGPTL-4 axis and that it does so by acting
directly on CCK receptors in adipocytes. We report that administration of CCK-8
(a bioactive fragment of CCK) to rats: (i) reduces plasma ANGTPL-4 levels; (ii)
represses Angptl-4 expression in WAT and (iii) simultaneously enhances LPL
activity in this tissue without inducing Lpl expression. In vivo CCK-8 effects
are specifically antagonized by the CCK-2 receptor (CCK-2R) antagonist, L
365,260. Moreover, CCK-8 downregulates Angptl-4 expression in wild-type pre
adipocytes, an effect that is not observed in engineered pre-adipocytes lacking
CCK-2R. These effects have functional consequences as CCK-8 was found to promote
the uptake of dietary fatty acids by WAT, as demonstrated by means of proton
nuclear magnetic resonance (1H-NMR). The efficacy of acute CCK-8 administration
was not reduced after chronic CCK-8 treatment. Moreover, the effects of CCK-8 on
WAT were not associated to the increase of circulating insulin. Our results show
that cholecystokinin promotes lipid storage in WAT by acting on adipocyte CCK-2R,
suggesting a pivotal role for CCK in TG homeostasis.
PMID- 29339380
TI - Negative regulation of the Keap1-Nrf2 pathway by a p62/Sqstm1 splicing variant.
AB - A key anti-oxidant pathway, the Keap1-Nrf2 system, is regulated by p62/Sqstm1 via
multiple mechanisms, including gene expression, post-translational modifications
such as ubiquitination and phosphorylation, and autophagic degradation of
p62/Sqstm1 and Keap1. Herein, we demonstrate a novel mode of regulation of the
Keap1-Nrf2 system, mediated by a splicing variant of p62/Sqstm1 pre-mRNA. Ensembl
database search and subsequent biochemical analyses in mice revealed the presence
of an mRNA that encodes p62/Sqstm1 protein lacking the Keap1-interacting region
(KIR), which is essential for the interaction with Keap1. Like full-length p62,
the variant was induced under conditions in which Nrf2 was activated (e.g.,
impairment of autophagy), oligomerized with itself and/or full-length protein,
and was degraded by autophagy. However, the variant failed to interact with Keap1
and sequester it into variant-positive aggregates. Remarkably, while full-length
p62 stabilized Nrf2 and induced the gene expression of Nrf2 targets, the variant
increased the amount of Keap1 and enhanced ubiquitination of Nrf2, thereby
suppressing the induction of Nrf2 targets. Hepatocytes isolated from genetically
modified mice that express full-length p62, but not the variant, were susceptible
to activation of Nrf2 in response to stress. Collectively, our results suggest
that splicing of p62/Sqstm1 pre-mRNA negatively regulates the Keap1-Nrf2 pathway.
PMID- 29339382
TI - In Vitro Susceptibility of Neisseria gonorrhoeae Strains to Mupirocin, an
Antibiotic Reformulated for Parenteral Administration in Nanoliposomes.
AB - Neisseria gonorrhoeae is an urgent antibiotic-resistant threat. This study
determined the MICs of mupirocin to be 0.0039 to 0.0625 MUg/ml for 94 N.
gonorrhoeae strains. Cross-resistance with other antibiotics was not detected.
Mupirocin, which is currently limited to topical administration, demonstrated
activity by injection when delivered in nanoliposomes. The nanoliposomal
formulation of mupirocin is a potential treatment for drug-resistant N.
gonorrhoeae.
PMID- 29339383
TI - New Shuttle Vectors for Gene Cloning and Expression in Multidrug-Resistant
Acinetobacter Species.
AB - Understanding bacterial pathogenesis requires adequate genetic tools to assess
the role of individual virulence determinants by mutagenesis and complementation
assays, as well as for homologous and heterologous expression of cloned genes.
Our knowledge of Acinetobacter baumannii pathogenesis has so far been limited by
the scarcity of genetic tools to manipulate multidrug-resistant (MDR) epidemic
strains, which are responsible for most infections. Here, we report on the
construction of new multipurpose shuttle plasmids, namely, pVRL1 and pVRL2, which
can efficiently replicate in Acinetobacter spp. and in Escherichia coli The pVRL1
plasmid has been constructed by combining (i) the cryptic plasmid pWH1277 from
Acinetobacter calcoaceticus, which provides an origin of replication for
Acinetobacter spp.; (ii) a ColE1-like origin of replication; (iii) the gentamicin
or zeocin resistance cassette for antibiotic selection; and (iv) a multilinker
containing several unique restriction sites. Modification of pVRL1 led to the
generation of the pVRL2 plasmid, which allows arabinose-inducible gene
transcription with an undetectable basal expression level of cloned genes under
uninduced conditions and a high dynamic range of responsiveness to the inducer.
Both pVRL1 and pVRL2 can easily be selected in MDR A. baumannii, have a narrow
host range and a high copy number, are stably maintained in Acinetobacter spp.,
and appear to be compatible with indigenous plasmids carried by epidemic strains.
Plasmid maintenance is guaranteed by the presence of a toxin-antitoxin system,
providing more insights into the mechanism of plasmid stability in Acinetobacter
spp.
PMID- 29339384
TI - A Novel Inhibitor of the LolCDE ABC Transporter Essential for Lipoprotein
Trafficking in Gram-Negative Bacteria.
AB - The outer membrane is an essential structural component of Gram-negative bacteria
that is composed of lipoproteins, lipopolysaccharides, phospholipids, and
integral beta-barrel membrane proteins. A dedicated machinery, called the Lol
system, ensures proper trafficking of lipoproteins from the inner to the outer
membrane. The LolCDE ABC transporter is the inner membrane component, which is
essential for bacterial viability. Here, we report a novel pyrrolopyrimidinedione
compound, G0507, which was identified in a phenotypic screen for inhibitors of
Escherichia coli growth followed by selection of compounds that induced the
extracytoplasmic sigmaE stress response. Mutations in lolC, lolD, and lolE
conferred resistance to G0507, suggesting LolCDE as its molecular target.
Treatment of E. coli cells with G0507 resulted in accumulation of fully processed
Lpp, an outer membrane lipoprotein, in the inner membrane. Using purified protein
complexes, we found that G0507 binds to LolCDE and stimulates its ATPase
activity. G0507 still binds to LolCDE harboring a Q258K substitution in LolC
(LolCQ258K), which confers high-level resistance to G0507 in vivo but no longer
stimulates ATPase activity. Our work demonstrates that G0507 has significant
promise as a chemical probe to dissect lipoprotein trafficking in Gram-negative
bacteria.
PMID- 29339385
TI - A Before-and-After Study of the Effectiveness of an Antimicrobial Stewardship
Program in Critical Care.
AB - We evaluated the use of antimicrobials expressed as defined daily doses (DDDs)
per 1,000 patient days and days of therapy (DOT) per 100 occupied bed-days in a
intensive care unit (ICU) of a general hospital in Barcelona, Spain, before and
after implementation of an antimicrobial stewardship (AMS) program (2007 to 2010
versus 2011 to 2015). The quarterly costs of antimicrobials used in the ICU and
its weight in the overall hospital costs of antimicrobials were calculated. The
effect of the applied AMS program on DDDs and DOT time series data was analyzed
by means of intervention time series analysis. A total of 5,002 patients were
included (1,971 for the first [before] period and 3,031 for the second [after]
period). The percentage of patients treated with one or more antimicrobials
decreased from 88.6 to 77.2% (P < 0.001). DDDs decreased from 246.8 to 192.3
(mean difference, -54.5; P = 0.001) and DOT from 66.7 to 54.6 (mean difference,
12.1; P = 0.066). The mean cost per trimester decreased from ?115,543 to ?73,477
(mean difference, -42,065.4 euros; P < 0.001), and the percentage of ICU
antimicrobials cost with respect to the total cost of hospital antimicrobials
decreased from 28.5 to 22.8% (mean difference, -5.59; P = 0.023). Implementation
of an AMS program in the ICU was associated with a marked reduction in the use of
antimicrobials, with cost savings close to one million euros since its
implementation. An AMS program can have a significant impact on optimizing
antimicrobial use in critical care practice.
PMID- 29339386
TI - Pterostilbene, a Potential MCR-1 Inhibitor That Enhances the Efficacy of
Polymyxin B.
AB - We characterized the synergistic effect produced between pterostilbene and
polymyxin B (fractional inhibitory concentration [FIC] index = 0.156 or 0.188)
against MCR-producing Escherichia coli strains of both human and animal origins.
The time-killing assays showed that either pterostilbene or polymyxin B failed to
eradicate the mcr-1- and NDM-positive E. coli strain ZJ487, but the combination
eliminated the strain by 1 h postinoculation. The survival rate of mice after
intraperitoneal infections was significantly enhanced from 0% to 60% in the group
in which combination therapy was applied.
PMID- 29339387
TI - Genetic Basis of Emerging Vancomycin, Linezolid, and Daptomycin Heteroresistance
in a Case of Persistent Enterococcus faecium Bacteremia.
AB - Whole-genome sequencing was used to examine a persistent Enterococcus faecium
bacteremia that acquired heteroresistance to three antibiotics in response to
prolonged multidrug therapy. A comparison of the complete genomes before and
after each change revealed the emergence of known resistance determinants for
vancomycin and linezolid and suggested that a novel mutation in fabF, encoding a
fatty acid synthase, was responsible for daptomycin nonsusceptibility. Plasmid
recombination contributed to the progressive loss of vancomycin resistance after
withdrawal of the drug.
PMID- 29339388
TI - Combating Carbapenem-Resistant Acinetobacter baumannii by an Optimized Imipenem
plus-Tobramycin Dosage Regimen: Prospective Validation via Hollow-Fiber Infection
and Mathematical Modeling.
AB - We aimed to prospectively validate an optimized combination dosage regimen
against a clinical carbapenem-resistant Acinetobacter baumannii (CRAB) isolate
(imipenem MIC, 32 mg/liter; tobramycin MIC, 2 mg/liter). Imipenem at constant
concentrations (7.6, 13.4, and 23.3 mg/liter, reflecting a range of clearances)
was simulated in a 7-day hollow-fiber infection model (inoculum, ~107.2 CFU/ml)
with and without tobramycin (7 mg/kg q24h, 0.5-h infusions). While monotherapies
achieved no killing or failed by 24 h, this rationally optimized combination
achieved >5 log10 bacterial killing and suppressed resistance.
PMID- 29339389
TI - In Vitro Antibiotic Susceptibility Pattern of Non-diphtheriae Corynebacterium
Isolates in Ontario, Canada, from 2011 to 2016.
AB - Non-diphtheriae Corynebacterium-associated disease has been increasingly observed
and often presents a conundrum to the treating physician. Analysis of antibiotic
susceptibility testing data for 1,970 clinical Corynebacterium isolates received
between 2011 and 2016 revealed that empirical drug treatment options are limited
to vancomycin and linezolid. Corynebacterium striatum was the most frequently
observed species during this study period, along with C. amycolatum and C.
pseudodiphtheriticum/C. propinquum Low levels of susceptibility to penicillin
(14.5%), erythromycin (15.1%), and clindamycin (8.7%) were observed for non
diphtheriae Corynebacterium species, while 3.0% of isolates were not susceptible
to daptomycin. Similarly, 26.9% and 38.1% of Corynebacterium isolates were
susceptible to ciprofloxacin and trimethoprim-sulfamethoxazole, respectively. Our
data show much lower susceptibility to penicillin than previously reported in the
literature and an increasing number of isolates resistant to daptomycin,
highlighting the need for continued antibiotic surveillance studies for
appropriate patient management and treatment success.
PMID- 29339391
TI - Intrapulmonary Pharmacokinetics of Lascufloxacin in Healthy Adult Volunteers.
AB - This study was performed to investigate the intrapulmonary penetration of
lascufloxacin in humans. Thirty healthy adult male Japanese subjects, allocated
into five groups, received lascufloxacin in a single oral dose of 75 mg.
Bronchoalveolar lavage and blood sampling were performed simultaneously in each
subject at 1, 2, 4, 6, or 24 h after administration, and lascufloxacin
concentrations in plasma, epithelial lining fluid, and alveolar macrophages were
determined. Lascufloxacin was rapidly distributed to the epithelial lining fluid
with a time to maximum drug concentration (Tmax) of 1 h, which was identical to
that in plasma. The maximum concentration of drug (Cmax) values in plasma,
epithelial lining fluid, and alveolar macrophages were 0.576, 12.3, and 21.8
MUg/ml, respectively. The corresponding area under the concentration-time curve
from 0 to 24 h (AUC0-24) values were 7.67, 123, and 325 MUg . h/ml. The mean drug
concentrations in the epithelial lining fluid and alveolar macrophages were much
higher than those in plasma at all time points examined, and the average site-to
free plasma concentration ratios fell within the ranges of 57.5 to 86.4 and 71.0
to 217, respectively. Drug levels in epithelial lining fluid and alveolar
macrophages exceeded the MIC90 values for common respiratory pathogens. (This
study was registered at JAPIC under registration number JapicCTI-142547.).
PMID- 29339390
TI - Identification of Hsp90 Inhibitors with Anti-Plasmodium Activity.
AB - Malaria remains a global health burden partly due to Plasmodium parasite
resistance to first-line therapeutics. The molecular chaperone heat shock protein
90 (Hsp90) has emerged as an essential protein for blood-stage Plasmodium
parasites, but details about its function during malaria's elusive liver stage
are unclear. We used target-based screens to identify compounds that bind to
Plasmodium falciparum and human Hsp90, which revealed insights into chemotypes
with species-selective binding. Using cell-based malaria assays, we demonstrate
that all identified Hsp90-binding compounds are liver- and blood-stage Plasmodium
inhibitors. Additionally, the Hsp90 inhibitor SNX-0723 in combination with the
phosphatidylinositol 3-kinase inhibitor PIK-75 synergistically reduces the liver
stage parasite load. Time course inhibition studies with the Hsp90 inhibitors and
expression analysis support a role for Plasmodium Hsp90 in late-liver-stage
parasite development. Our results suggest that Plasmodium Hsp90 is essential to
liver- and blood-stage parasite infections and highlight an attractive route for
development of species-selective PfHsp90 inhibitors that may act synergistically
in combination therapies to prevent and treat malaria.
PMID- 29339392
TI - A Novel Piperazine-Based Drug Lead for Cryptosporidiosis from the Medicines for
Malaria Venture Open-Access Malaria Box.
AB - Cryptosporidiosis causes life-threatening diarrhea in children under the age of 5
years and prolonged diarrhea in immunodeficient people, especially AIDS patients.
The standard of care, nitazoxanide, is modestly effective in children and
ineffective in immunocompromised individuals. In addition to the need for new
drugs, better knowledge of drug properties that drive in vivo efficacy is needed
to facilitate drug development. We report the identification of a piperazine
based lead compound for Cryptosporidium drug development, MMV665917, and a new
pharmacodynamic method used for its characterization. The identification of
MMV665917 from the Medicines for Malaria Venture Malaria Box was followed by dose
response studies, in vitro toxicity studies, and structure-activity relationship
studies using commercial analogues. The potency of this compound against
Cryptosporidium parvum Iowa and field isolates was comparable to that against
Cryptosporidium hominis Furthermore, unlike nitazoxanide, clofazimine, and
paromomycin, MMV665917 appeared to be curative in a NOD SCID gamma mouse model of
chronic cryptosporidiosis. MMV665917 was also efficacious in a gamma interferon
knockout mouse model of acute cryptosporidiosis. To determine if efficacy in this
mouse model of chronic infection might relate to whether compounds are
parasiticidal or parasitistatic for C. parvum, we developed a novel in vitro
parasite persistence assay. This assay suggested that MMV665917 was
parasiticidal, unlike nitazoxanide, clofazimine, and paromomycin. The assay also
enabled determination of the concentration of the compound required to maximize
the rate of parasite elimination. This time-kill assay can be used to prioritize
early-stage Cryptosporidium drug leads and may aid in planning in vivo efficacy
experiments. Collectively, these results identify MMV665917 as a promising lead
and establish a new method for characterizing potential anticryptosporidial
agents.
PMID- 29339393
TI - Early Clinical Assessment of the Antimicrobial Activity of Finafloxacin Compared
to Ciprofloxacin in Subsets of Microbiologically Characterized Isolates.
AB - Two phase II studies were performed with patients with uncomplicated urinary
tract infections (uUTIs) and complicated urinary tract infections (cUTIs) or
acute pyelonephritis (PN) to compare finafloxacin (300 mg twice a day [b.i.d.]
orally for uUTI and 800 mg once a day [q.d.] intravenously [i.v.] for cUTI/PN)
and ciprofloxacin (250 mg b.i.d. orally for uUTI and 400 mg b.i.d. i.v. for
cUTI/PN). The early response to the study medications was evaluated in the
microbiological intent-to-treat population (mITT) at day 3. A total of 21% of the
isolates were ciprofloxacin resistant, 13.7% were primed pathogens carrying a
mutation(s) potentially fostering fluoroquinolone resistance development, and
7.1% produced extended-spectrum beta-lactamases (ESBLs). Finafloxacin
demonstrated very good early clinical activity, with microbiological eradication
rates of 88.6% (n = 132), compared to 78.7% (n = 61) for ciprofloxacin, and 69.6%
(n = 23), compared to 35.7% (n = 14) for ciprofloxacin, in patients with
ciprofloxacin-resistant uropathogens; 94.1% (n = 17), compared to 80.0% (n = 10)
for ciprofloxacin, in patients infected with uropathogens primed for
fluoroquinolone resistance uropathogens; and 91.7% (n = 11), compared to 0% for
ciprofloxacin, in patients infected with ESBL producers. Finafloxacin
demonstrated early and rapid activity against uropathogens, including
fluoroquinolone-resistant and/or multiresistant pathogens or ESBL producers,
while ciprofloxacin was less active against this subset of resistant pathogens.
Susceptibilities of pathogens were quantitated by broth microdilution. Isolates
were subgrouped according to their susceptibility patterns, in particular first
step quinolone resistance, quinolone resistance, and ESBL production. Eradication
was defined as the elimination or reduction of study entry pathogens to <103
CFU/ml in urine culture. (The studies described in this paper have been
registered at ClinicalTrials.gov under identifiers NCT00722735 and NCT01928433.).
PMID- 29339394
TI - Population Pharmacokinetics of Finafloxacin in Healthy Volunteers and Patients
with Complicated Urinary Tract Infections.
AB - Finafloxacin is a novel fluoroquinolone with increased antibacterial activity at
acidic pH and reduced susceptibility to several resistance mechanisms. A phase II
study revealed a good efficacy/safety profile in patients with complicated
urinary tract infections (cUTIs), while the pharmacokinetics was characterized by
highly variable concentration-versus-time profiles, suggesting the need for an
elaborated pharmacokinetic model. Data from three clinical trials were evaluated:
127 healthy volunteers were dosed orally (n = 77) or intravenously (n = 50), and
139 patients with cUTI received finafloxacin intravenously. Plasma (2,824 samples
from volunteers and 414 samples from patients) and urine (496 samples from
volunteers and 135 samples patients) concentrations were quantified by liquid
chromatography-tandem mass spectrometry (LC-MS/MS). NONMEM was used to build a
population pharmacokinetic model, and pharmacokinetic/pharmacodynamic
relationships were investigated via simulations and logistic regression. A two
compartment model with first-order elimination described the data best (central
volume of distribution [Vc] and peripheral volume of distribution [Vp] of 47
liters [20%] and 43 liters [67%], respectively, and elimination clearance and
intercompartmental clearance of 21 liters/h [54%] and 2.8 liters/h [57%],
respectively [median bootstrap estimates {coefficients of variation}]). Vc
increased with body surface area, and clearance was reduced in patients (-29%).
Oral absorption was described best by parallel first- and zero-order processes
(bioavailability of 75%). No pharmacodynamic surrogate parameter of
clinical/microbiological outcome could be identified, which depended exclusively
on the MIC of the causative pathogens. Despite the interindividual variability,
the present data set does not support covariate-based dose adjustments. Based on
the favorable safety and efficacy data, the clinical relevance of the observed
variability appears to be limited. (This study has been registered at
ClinicalTrials.gov under identifier NCT01928433.).
PMID- 29339395
TI - Explorative Randomized Phase II Clinical Study of the Efficacy and Safety of
Finafloxacin versus Ciprofloxacin for Treatment of Complicated Urinary Tract
Infections.
AB - The broad-spectrum C-8-cyano-fluoroquinolone finafloxacin displays enhanced
activity under acidic conditions. This phase II clinical study compared the
efficacies and safeties of finafloxacin and ciprofloxacin in patients with
complicated urinary tract infection and/or pyelonephritis. A 5-day regimen with
800 mg finafloxacin once a day (q.d.) (FINA05) had results similar to those of a
10-day regimen with 800 mg finafloxacin q.d. (FINA10). Combined microbiological
and clinical responses at the test-of-cure (TOC) visit were 70% for FINA05, 68%
for FINA10, and 57% for a 10-day ciprofloxacin regimen (CIPRO10) in 193 patients
(64 for FINA05, 68 for FINA10, and 61 for CIPRO10) of the microbiological intent
to-treat (mITT) population. Additionally, the clinical effects of ciprofloxacin
on patients with an acidic urine pH (80% of patients) were reduced, whereas the
effects of finafloxacin were unchanged. Finafloxacin was safe and well tolerated.
Overall, 43.4% of the patients in the FINA05 group, 42.7% in the FINA10 group,
and 54.2% in the CIPRO10 group experienced mostly mild and treatment-emergent but
unrelated adverse events. A short-course regimen of 5 days of finafloxacin
resulted in high eradication and improved clinical outcome rates compared to
those for treatment with ciprofloxacin for 10 days. In contrast to those of
ciprofloxacin, the clinical effects of finafloxacin were not reduced by acidic
urine pH. Hospitalized adults were randomized 1:1:1 to finafloxacin treatment
(800 mg q.d.) for either 5 or 10 days or to ciprofloxacin treatment (400 mg/500
mg b.i.d.) for 10 days with an optional switch from intravenous (i.v.) to oral
administration at day 3. The primary endpoint was the combined microbiological
and clinical response at the TOC visit in the microbiological intent-to-treat
population. (This study has been registered at ClinicalTrials.gov under
identifier NCT01928433.).
PMID- 29339396
TI - Efficacy of Apramycin against Multidrug-Resistant Acinetobacter baumannii in the
Murine Neutropenic Thigh Model.
AB - Apramycin, an aminocyclitol aminoglycoside, was rapidly bactericidal against
Acinetobacter baumannii In a neutropenic murine thigh infection model, treatment
associated A. baumannii CFU reductions of >4 log10 per thigh were observed for
all exposures for which area under the curve (AUC)/MIC ratio was >50 and maximum
concentration of drug in serum (Cmax)/MIC was ~10 or higher. Based on these
findings, we suggest that apramycin deserves further preclinical exploration as a
repurposed therapeutic for multidrug-resistant Gram-negative pathogens, including
A. baumannii.
PMID- 29339398
TI - Assay Conditions Influence Affinities of Rat Organic Cation Transporter 1:
Analysis of Mutagenesis in the Modeled Outward-Facing Cleft by Measuring Effects
of Substrates and Inhibitors on Initial Uptake.
AB - The effects of mutations in the modeled outward-open cleft of rat organic cation
transporter 1 (rOCT1) on affinities of substrates and inhibitors were
investigated. Human embryonic kidney 293 cells were stably transfected with rOCT1
or rOCT1 mutants, and uptake of the substrates 1-methyl-4-phenylpyridinium+
(MPP+) and tetraethylammonium+ (TEA+) or inhibition of MPP+ uptake by the
nontransported inhibitors tetrabutylammonium+ (TBuA+), tetrapentylammonium+
(TPeA+), and corticosterone was measured. Uptake measurements were performed on
confluent cell layers using a 2-minute incubation or in dissociated cells using
incubation times of 1, 5, or 10 seconds. With both methods, different apparent
Michaelis-Menten constant (Km) values, different IC50 values, and varying effects
of mutations were determined. In addition, varying IC50 values for the inhibition
of MPP+ uptake and varying effects of mutations were obtained when different MPP+
concentrations far below the apparent Km value were used for uptake measurements.
Eleven mutations were investigated by measuring initial uptake in dissociated
cells and employing 0.1 uM MPP+ for uptake during inhibition experiments. Altered
affinities for substrates and/or inhibitors were observed when Phe160, Trp218,
Arg440, Leu447, and Asp475 were mutated. The mutations resulted in changes of
apparent Km values for TEA+ and/or MPP+ Mutation of Trp218 and Asp475 led to
altered IC50 values for TBuA+, TPeA+, and corticosterone, whereas the mutation of
Phe160 and Leu447 changed the IC50 values for two inhibitors. Thereby amino acids
in the outward-facing conformation of rOCT1 could be identified that interact
with structurally different inhibitors and probably also with different
substrates.
PMID- 29339397
TI - Heat Shock Factor HsfA1a Is Essential for R Gene-Mediated Nematode Resistance and
Triggers H2O2 Production1.
AB - Plants generate reactive oxygen species (ROS) in the apoplast in response to
pathogen attack, especially following resistance (R) gene-mediated pathogen
recognition; however, the mechanisms activating ROS generation remain unknown.
Here, we demonstrate that RKN (Meloidogyne incognita) infection rapidly induces
ROS accumulation in the roots of tomato (Solanum lycopersicum) plants that
contain the R gene Mi-1.2 but rarely induces ROS accumulation in the susceptible
or Mi-1.2-silenced resistant genotypes. RNK also induces the hypersensitive
response, a form of programmed cell death, in Mi-1.2 plants. RKN induces the
expression of numerous class-A heat shock factor (HsfA) genes in resistant tomato
plants. Silencing HsfA1a compromises Mi-1.2-mediated resistance, apoplastic H2O2
accumulation, and the transcription of whitefly induced 1 (Wfi1), which encodes a
respiratory burst oxidase homolog. HsfA1a regulates Wfi1 transcription by binding
to the Wfi1 promoter, and silencing of Wfi1 compromises Mi-1.2-mediated
resistance. HsfA1a and Wfi1 are involved in Mi-1.2-triggered Hsp90 accumulation
and basal defense in susceptible tomato. Thus, HsfA-1aWfi1-dependent ROS
signaling functions as a crucial regulator of plant defense responses.
PMID- 29339399
TI - Ovariectomy-induced bone loss in TNFalpha and IL6 gene knockout mice is regulated
by different mechanisms.
AB - We examined the effects of tumor necrosis factor-alpha (TNFalpha) and interleukin
6 (IL6) gene knockout in preserving the bone loss induced by ovariectomy (OVX)
and the mechanisms involved in bone metabolism. Twenty female wild-type (WT),
TNFalpha-knockout (TNFalpha-/-) or IL6-knockout (IL6-/-) mice aged 12 weeks were
sham-operated (SHAM) or subjected to OVX and killed after 4 weeks. Bone mass and
skeletal microarchitecture were determined using micro-CT. Bone marrow stromal
cells (BMSCs) from all three groups (WT, TNFalpha-/- and IL6-/-) were induced to
differentiate into osteoblasts or osteoclasts and treated with 17-beta-estradiol.
Bone metabolism was assessed by histological analysis, serum analyses and qRT
PCR. OVX successfully induced a high turnover in all mice, but a repair effect
was observed in TNFalpha-/- and IL6-/- mice. The ratio of femoral trabecular bone
volume to tissue volume, trabecular number and trabecular thickness were
significantly decreased in WT mice subjected to OVX, but increased in TNFalpha-/-
mice (1.62, 1.34, 0.27-fold respectively; P < 0.01) and IL6-/- mice (1.34, 0.80,
0.22-fold respectively; P < 0.01). Furthermore, we observed a 29.6% increase in
the trabecular number in TNFalpha-/- mice when compared to the IL6-/- mice. Both,
TNFalpha-/- and IL6-/- BMSCs exhibited decreased numbers of TRAP-positive cells
and an increase in ALP-positive cells, with or without E2 treatment (P < 0.05).
While the knockout of TNFalpha or IL6 significantly upregulated mRNA expressions
of osteoblast-related genes (Runx2 and Col1a1) and downregulated osteoclast
related mRNA for TRAP, MMP9 and CTSK in vivo and in vitro, TNFalpha knockout
appeared to have roles beyond IL6 knockout in upregulating Col1a1 mRNA expression
and downregulating mRNA expressions of WNT-related genes (DKK1 and Sost) and TNF
related activation-induced genes (TRAF6). TNFalpha seemed to be more potentially
invasive in inhibiting bone formation and enhancing TRAF6-mediated
osteoclastogenesis than IL6, implying that the regulatory mechanisms of TNFalpha
and IL6 in bone metabolism may be different.
PMID- 29339400
TI - Intact glucose uptake despite deteriorating signaling in adipocytes with high-fat
feeding.
AB - To capture immediate cellular changes during diet-induced expansion of adipocyte
cell volume and number, we characterized mature adipocytes during a short-term
high-fat diet (HFD) intervention. Male C57BL6/J mice were fed chow diet, and then
switched to HFD for 2, 4, 6 or 14 days. Systemic glucose clearance was assessed
by glucose tolerance test. Adipose tissue was dissected for RNA-seq and cell size
distribution analysis using coulter counting. Insulin response in isolated
adipocytes was monitored by glucose uptake assay and Western blotting, and
confocal microscopy was used to assess autophagic activity. Switching to HFD was
accompanied by an immediate adipocyte size expansion and onset of systemic
insulin resistance already after two days, followed by recruitment of new
adipocytes. Despite an initially increased non-stimulated and preserved insulin
stimulated glucose uptake, we observed a decreased phosphorylation of insulin
receptor substrate-1 (IRS-1) and protein kinase B (PKB). After 14 days of HFD,
both the insulin-stimulated phosphorylation of Akt substrate of 160 kDa (AS160)
and glucose uptake was blunted. RNA-seq analysis of adipose tissue revealed
transient changes in gene expression at day four, including highly significant
upregulation of Trp53inp, previously demonstrated to be involved in autophagy. We
confirmed increased autophagy, measured as an increased density of LC3-positive
puncta and decreased p62 expression after 14 days of HFD. In conclusion, HFD
rapidly induced systemic insulin resistance, whereas insulin-stimulated glucose
uptake remained intact throughout 6 days of HFD feeding. We also identified
autophagy as an early cellular process that potentially influences adipocyte
function upon switching to HFD.
PMID- 29339401
TI - The impact of preload reduction with head-up tilt testing on longitudinal and
transverse left ventricular mechanics: a study utilizing deformation volume
analysis.
AB - BACKGROUND: Left ventricular (LV) function is dependent on load, intrinsic
contractility and relaxation with a variable impact on specific mechanics. Strain
(epsilon) imaging allows the assessment of cardiac function; however, the direct
relationship between volume and strain is currently unknown. The aim of this
study was to establish the impact of preload reduction through head-up tilt (HUT)
testing on simultaneous left ventricular (LV) longitudinal and transverse
function and their respective contribution to volume change. METHODS: A focused
transthoracic echocardiogram was performed on 10 healthy male participants (23 +/
3 years) in the supine position and following 1 min and 5 min of HUT testing.
Raw temporal longitudinal epsilon (Ls) and transverse epsilon (Ts) values were
exported and divided into 5% increments across the cardiac cycle and
corresponding LV volumes were traced at each 5% increment. This provided
simultaneous LV longitudinal and transverse epsilon and volume loops (deformation
volume analysis - DVA). RESULTS: There was a leftward shift of the epsilon-volume
loop from supine to 1 min and 5 min of HUT (P < 0.001). Moreover, longitudinal
shortening was reduced (P < 0.001) with a concomitant increase in transverse
thickening from supine to 1 min, which was further augmented at 5 min (P =
0.018). CONCLUSIONS: Preload reduction occurs within 1 min of HUT but does not
further reduce at 5 min. This decline is associated with a decrease in
longitudinal epsilon and concomitant increase in transverse epsilon.
Consequently, augmented transverse relaxation appears to be an important factor
in the maintenance of LV filling in the setting of reduced preload. DVA provides
information on the relative contribution of mechanics to a change in LV volume
and may have a role in the assessment of clinical populations.
PMID- 29339402
TI - Canonical Notch signaling is dispensable for adult steady-state and stress myelo
erythropoiesis.
AB - Although an essential role for canonical Notch signaling in generation of
hematopoietic stem cells in the embryo and in thymic T-cell development is well
established, its role in adult bone marrow (BM) myelopoiesis remains unclear.
Some studies, analyzing myeloid progenitors in adult mice with inhibited Notch
signaling, implicated distinct roles of canonical Notch signaling in regulation
of progenitors for the megakaryocyte, erythroid, and granulocyte-macrophage cell
lineages. However, these studies might also have targeted other pathways.
Therefore, we specifically deleted, in adult BM, the transcription factor
recombination signal-binding protein J kappa (Rbpj), through which canonical
signaling from all Notch receptors converges. Notably, detailed progenitor
staging established that canonical Notch signaling is fully dispensable for all
investigated stages of megakaryocyte, erythroid, and myeloid progenitors in
steady state unperturbed hematopoiesis, after competitive BM transplantation, and
in stress-induced erythropoiesis. Moreover, expression of key regulators of these
hematopoietic lineages and Notch target genes were unaffected by Rbpj deficiency
in BM progenitor cells.
PMID- 29339403
TI - A phase 1 study of azacitidine combined with chemotherapy in childhood leukemia:
a report from the TACL consortium.
PMID- 29339404
TI - Hif-1alpha and Hif-2alpha regulate hemogenic endothelium and hematopoietic stem
cell formation in zebrafish.
AB - During development, hematopoietic stem cells (HSCs) derive from specialized
endothelial cells (ECs) called hemogenic endothelium (HE) via a process called
endothelial-to-hematopoietic transition (EHT). Hypoxia-inducible factor-1alpha
(HIF-1alpha) has been reported to positively modulate EHT in vivo, but current
data indicate the existence of other regulators of this process. Here we show
that in zebrafish, Hif-2alpha also positively modulates HSC formation.
Specifically, HSC marker gene expression is strongly decreased in hif-1aa;hif-1ab
(hif-1alpha) and in hif-2aa;hif-2ab (hif-2alpha) zebrafish mutants and morphants.
Moreover, live imaging studies reveal a positive role for hif-1alpha and hif
2alpha in regulating HE specification. Knockdown of hif-2alpha in hif-1alpha
mutants leads to a greater decrease in HSC formation, indicating that hif-1alpha
and hif-2alpha have partially overlapping roles in EHT. Furthermore, hypoxic
conditions, which strongly stimulate HSC formation in wild-type animals, have
little effect in the combined absence of Hif-1alpha and Hif-2alpha function. In
addition, we present evidence for Hif and Notch working in the same pathway
upstream of EHT. Both notch1a and notch1b mutants display impaired EHT, which
cannot be rescued by hypoxia. However, overexpression of the Notch intracellular
domain in ECs is sufficient to rescue the hif-1alpha and hif-2alpha morphant EHT
phenotype, suggesting that Notch signaling functions downstream of the Hif
pathway during HSC formation. Altogether, our data provide genetic evidence that
both Hif-1alpha and Hif-2alpha regulate EHT upstream of Notch signaling.
PMID- 29339405
TI - Health care professionals' neckties as a source of transmission of bacteria to
patients: a systematic review.
AB - BACKGROUND: There is growing concern that neckties worn by health care
professionals may contribute to infections contracted in health care settings. We
evaluated the evidence for health-care-associated infections resulting from
neckties and whether the evidence is sufficient to warrant a tieless policy in
Canada. METHODS: We performed a systematic review to determine whether neckties
worn by health care professionals colonize harmful pathogenic bacteria and
whether they contribute to the spread of infection to patients in the inpatient
or outpatient setting. We searched PubMed (1966 to 2017) and Embase (1974 to
2017). The level of evidence was appraised according to the Oxford Centre for
Evidence-Based Medicine levels of evidence. We evaluated the quality of evidence
and the risk of bias using the Jadad scale or the Newcastle-Ottawa Scale.
RESULTS: We screened 1675 citations, of which 6 were ultimately included in the
systematic review. Only 1 study gave level 1b evidence (randomized controlled
trial). Neckties were more likely than shirt pockets to colonize bacteria. There
is limited evidence that neckties may be contaminated with pathogenic bacteria
(e.g., methicillin-resistant Staphylococcus aureus) and very limited evidence
that contaminated neckties may transmit bacteria (in a controlled experimental
setting to a mannequin). INTERPRETATION: There is no evidence of increased rates
of health-care-associated infections related to the wearing of neckties by health
care professionals. There is weak evidence that neckties are contaminated with
pathogenic (and nonpathogenic) bacteria. The level of evidence was weak and the
studies were heterogeneous. Evidence to support the need for a tieless dress code
policy is lacking.
PMID- 29339406
TI - Genetic Diversity, Molecular Phylogeny, and Selection Evidence of Jinchuan Yak
Revealed by Whole-Genome Resequencing.
AB - Jinchuan yak, a newly discovered yak breed, not only possesses a large proportion
of multi-ribs but also exhibits many good characteristics, such as high meat
production, milk yield, and reproductive performance. However, there is limited
information about its overall genetic structure, relationship with yaks in other
areas, and possible origins and evolutionary processes. In this study, 7,693,689
high-quality single-nucleotide polymorphisms were identified by resequencing the
genome of Jinchuan yak. Principal component and population genetic structure
analyses showed that Jinchuan yak could be distinguished as an independent
population among the domestic yak population. Linkage disequilibrium analysis
showed that the decay rate of Jinchuan yak was the lowest of the domestic yak
breeds, indicating that the degree of domestication and selection intensity of
Jinchuan yak were higher than those of other yak breeds. Combined with
archaeological data, we speculated that the origin of domestication of Jinchuan
yak was ~6000 yr ago (4000-10,000 yr ago). The quantitative dynamics of
population growth history in Jinchuan yak was similar to that of other breeds of
domestic and wild yaks, but was closer to that of the wild yak. No significant
gene exchange between Jinchuan and other domestic yaks occurred. Compared with
other domestic yaks, Jinchuan yak possessed 339 significantly and positively
selected genes, several of which relate to physiological rhythm, histones, and
the breed's excellent production characteristics. Our results provide a basis for
the discovery of the evolution, molecular origin, and unique traits of Jinchuan
yak.
PMID- 29339407
TI - Genomic Identification and Functional Characterization of Essential Genes in
Caenorhabditis elegans.
AB - Using combined genetic mapping, Illumina sequencing, bioinformatics analyses, and
experimental validation, we identified 60 essential genes from 104 lethal
mutations in two genomic regions of Caenorhabditis elegans totaling ~14 Mb on
chromosome III(mid) and chromosome V(left). Five of the 60 genes had not
previously been shown to have lethal phenotypes by RNA interference depletion. By
analyzing the regions around the lethal missense mutations, we identified four
putative new protein functional domains. Furthermore, functional characterization
of the identified essential genes shows that most are enzymes, including
helicases, tRNA synthetases, and kinases in addition to ribosomal proteins. Gene
Ontology analysis indicated that essential genes often encode for enzymes that
conduct nucleic acid binding activities during fundamental processes, such as
intracellular DNA replication, transcription, and translation. Analysis of
essential gene shows that they have fewer paralogs, encode proteins that are in
protein interaction hubs, and are highly expressed relative to nonessential
genes. All these essential gene traits in C. elegans are consistent with those of
human disease genes. Most human orthologs (90%) of the essential genes in this
study are related to human diseases. Therefore, functional characterization of
essential genes underlines their importance as proxies for understanding the
biological functions of human disease genes.
PMID- 29339408
TI - Development of the Swimbladder Surfactant System and Biogenesis of Lysosome
Related Organelles Is Regulated by BLOS1 in Zebrafish.
AB - Hermansky-Pudlak syndrome (HPS) is a human autosomal recessive disorder that is
characterized by oculocutaneous albinism and a deficiency of the platelet storage
pool resulting from defective biogenesis of lysosome-related organelles (LROs).
To date, 10 HPS genes have been identified, three of which belong to the octamer
complex BLOC-1 (biogenesis of lysosome-related organelles complex 1). One subunit
of the BLOC-1 complex, BLOS1, also participates in the BLOC-1-related complex
(BORC). Due to lethality at the early embryo stage in BLOS1 knockout mice, the
function of BLOS1 in the above two complexes and whether it has a novel function
are unclear. Here, we generated three zebrafish mutant lines with a BLOC-1
deficiency, in which melanin and silver pigment formation was attenuated as a
result of mutation of bloc1s1, bloc1s2, and dtnbp1a, suggesting that they
function in the same complex. In addition, mutations of bloc1s1 and bloc1s2
caused an accumulation of clusters of lysosomal vesicles at the posterior part of
the tectum, representing a BORC-specific function in zebrafish. Moreover, bloc1s1
is highly expressed in the swimbladder during postembryonic stages and is
required for positively regulating the expression of the genes, which is known to
govern surfactant production and lung development in mammals. Our study
identified BLOS1 as a crucial regulator of the surfactant system. Thus, the
zebrafish swimbladder might be an easy system to screen and study genetic
modifiers that control surfactant production and homeostasis.
PMID- 29339409
TI - Impact of Homologous Recombination on Silent Chromatin in Saccharomyces
cerevisiae.
AB - Specialized chromatin domains repress transcription of genes within them and
present a barrier to many DNA-protein interactions. Silent chromatin in the
budding yeast Saccharomyces cerevisiae, akin to heterochromatin of metazoans and
plants, inhibits transcription of PolII- and PolIII-transcribed genes, yet
somehow grants access to proteins necessary for DNA transactions like replication
and homologous recombination. In this study, we adapted a novel assay to detect
even transient changes in the dynamics of transcriptional silencing at HML after
it served as a template for homologous recombination. Homologous recombination
specifically targeted to HML via double-strand-break formation at a homologous
locus often led to transient loss of transcriptional silencing at HML
Interestingly, many cells could template homology-directed repair at HML without
an obligate loss of silencing, even in recombination events with extensive gene
conversion tracts. In a population of cells that experienced silencing loss
following recombination, transcription persisted for 2-3 hr after all double
strand breaks were repaired. mRNA levels from cells that experienced
recombination-induced silencing loss did not approach the amount of mRNA seen in
cells lacking transcriptional silencing. Thus, silencing loss at HML after
homologous recombination was short-lived and limited.
PMID- 29339410
TI - Maintenance of Genome Integrity by Mi2 Homologs CHD-3 and LET-418 in
Caenorhabditis elegans.
AB - Meiotic recombination depends upon the tightly coordinated regulation of
chromosome dynamics and is essential for the production of haploid gametes.
Central to this process is the formation and repair of meiotic double-stranded
breaks (DSBs), which must take place within the constraints of a specialized
chromatin architecture. Here, we demonstrate a role for the nucleosome remodeling
and deacetylase (NuRD) complex in orchestrating meiotic chromosome dynamics in
Caenorhabditis elegans Our data reveal that the conserved Mi2 homologs
Chromodomain helicase DNA-binding protein (CHD-3) and its paralog LET-418
facilitate meiotic progression by ensuring faithful repair of DSBs through
homologous recombination. We discovered that loss of either CHD-3 or LET-418
results in elevated p53-dependent germ line apoptosis, which relies on the
activation of the conserved checkpoint kinase CHK-1 Consistent with these
findings, chd-3 and let-418 mutants produce a reduced number of offspring,
indicating a role for Mi2 in forming viable gametes. When Mi2 function is
compromised, persisting recombination intermediates are detected in late
pachytene nuclei, indicating a failure in the timely repair of DSBs.
Intriguingly, our data indicate that in Mi2 mutant germ lines, a subset of DSBs
are repaired by nonhomologous end joining, which manifests as chromosomal
fusions. We find that meiotic defects are exacerbated in Mi2 mutants lacking CKU
80, as evidenced by increased recombination intermediates, corpses, and defects
in chromosomal integrity. Taken together, our findings support a model wherein
the C. elegans Mi2 complex maintains genomic integrity through reinforcement of a
chromatin landscape suitable for homology-driven repair mechanisms.
PMID- 29339411
TI - Flagellin Glycoproteomics of the Periodontitis Associated Pathogen Selenomonas
sputigena Reveals Previously Not Described O-glycans and Rhamnose Fragment
Rearrangement Occurring on the Glycopeptides.
AB - Flagellated, Gram-negative, anaerobic, crescent-shaped Selenomonas species are
colonizers of the digestive system, where they act at the interface between
health and disease. Selenomonas sputigena is also considered a potential human
periodontal pathogen, but information on its virulence factors and underlying
pathogenicity mechanisms is scarce. Here we provide the first report of a
Selenomonas glycoprotein, showing that S. sputigena produces a diversely and
heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which
carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O
glycans in the range from mono- to hexasaccharides. A comprehensive glycomic and
glycoproteomic assessment revealed extensive glycan macro- and microheterogeneity
identified from 22 unique glycopeptide species. From the multiple sites of
glycosylation, five were unambiguously identified on the 437-amino acid C9LY14
protein (Thr149, Ser182, Thr199, Thr259, and Ser334), the only flagellin protein
identified. The O-glycans additionally showed modifications by methylation and
putative acetylation. Some O-glycans carried hitherto undescribed
residues/modifications as determined by their respective m/z values, reflecting
the high diversity of native S. sputigena flagellin. We also found that
monosaccharide rearrangement occurred during collision-induced dissociation (CID)
of protonated glycopeptide ions. This effect resulted in pseudo Y1-glycopeptide
fragment ions that indicated the presence of additional glycosylation sites on a
single glycopeptide. CID oxonium ions and electron transfer dissociation,
however, confirmed that just a single site was glycosylated, showing that glycan
to-peptide rearrangement can occur on glycopeptides and that this effect is
influenced by the molecular nature of the glycan moiety. This effect was most
pronounced with disaccharides. This study is the first report on O-linked
flagellin glycosylation in a Selenomonas species, revealing that C9LY14 is one of
the most heavily glycosylated flagellins described to date. This study
contributes to our understanding of the largely under-investigated surface
properties of oral bacteria. The data have been deposited to the ProteomeXchange
with identifier PXD005859.
PMID- 29339412
TI - The Sequence-specific Peptide-binding Activity of the Protein Sulfide Isomerase
AGR2 Directs Its Stable Binding to the Oncogenic Receptor EpCAM.
AB - AGR2 is an oncogenic endoplasmic reticulum (ER)-resident protein disulfide
isomerase. AGR2 protein has a relatively unique property for a chaperone in that
it can bind sequence-specifically to a specific peptide motif (TTIYY). A
synthetic TTIYY-containing peptide column was used to affinity-purify AGR2 from
crude lysates highlighting peptide selectivity in complex mixtures. Hydrogen
deuterium exchange mass spectrometry localized the dominant region in AGR2 that
interacts with the TTIYY peptide to within a structural loop from amino acids 131
135 (VDPSL). A peptide binding site consensus of Tx[IL][YF][YF] was developed for
AGR2 by measuring its activity against a mutant peptide library. Screening the
human proteome for proteins harboring this motif revealed an enrichment in
transmembrane proteins and we focused on validating EpCAM as a potential AGR2
interacting protein. AGR2 and EpCAM proteins formed a dose-dependent protein
protein interaction in vitro Proximity ligation assays demonstrated that
endogenous AGR2 and EpCAM protein associate in cells. Introducing a single
alanine mutation in EpCAM at Tyr251 attenuated its binding to AGR2 in vitro and
in cells. Hydrogen-deuterium exchange mass spectrometry was used to identify a
stable binding site for AGR2 on EpCAM, adjacent to the TLIYY motif and
surrounding EpCAM's detergent binding site. These data define a dominant site on
AGR2 that mediates its specific peptide-binding function. EpCAM forms a model
client protein for AGR2 to study how an ER-resident chaperone can dock
specifically to a peptide motif and regulate the trafficking a protein destined
for the secretory pathway.
PMID- 29339413
TI - Proteotranscriptomic Analysis and Discovery of the Profile and Diversity of Toxin
like Proteins in Centipede.
AB - Centipedes are one of the oldest venomous animals and use their venoms as weapons
to attack prey or protect themselves. Their venoms contain various components
with different biomedical and pharmacological properties. However, little
attention has been paid to the profiles and diversity of their toxin-like
proteins/peptides. In this study, we used a proteotranscriptomic approach to
uncover the diversity of centipede toxin-like proteins in Scolopendra subspinipes
mutilans Nine hundred twenty-three and 6,736 peptides, which were separately
isolated from venom and torso tissues, respectively, were identified by ESI-MS/MS
and deduced from their transcriptomes. Finally, 1369 unique proteins were
identified in the proteome, including 100 proteins that exhibited overlapping
expression in venom and torso tissues. Of these proteins, at least 40 proteins
were identified as venom toxin-like proteins. Meanwhile, transcriptome mining
identified ~10-fold more toxin-like proteins and enabled the characterization of
the precursor architecture of mature toxin-like peptides. Importantly, combined
with proteomic and transcriptomic analyses, 25 toxin-like proteins/peptides
(neurotoxins accounted for 50%) were expressed outside the venom gland and
involved in gene recruitment processes. These findings highlight the extensive
diversity of centipede toxin-like proteins and provide a new foundation for the
medical-pharmaceutical use of centipede toxin-like proteins. Moreover, we are the
first group to report the gene recruitment activity of venom toxin-like proteins
in centipede, similar to snakes.
PMID- 29339414
TI - Assembly of Methyl Coenzyme M Reductase in the Methanogenic Archaeon
Methanococcus maripaludis.
AB - Methyl coenzyme M reductase (MCR) is a complex enzyme that catalyzes the final
step in biological methanogenesis. To better understand its assembly, the
recombinant MCR from the thermophile Methanothermococcus okinawensis (rMCRok) was
expressed in the mesophile Methanococcus maripaludis The rMCRok was
posttranslationally modified correctly and contained McrD and the unique nickel
tetrapyrrole coenzyme F430 Subunits of the native M. maripaludis (MCRmar) were
largely absent, suggesting that the recombinant enzyme was formed by an assembly
of cotranscribed subunits. Strong support for this hypothesis was obtained by
expressing a chimeric operon comprising the His-tagged mcrA from M. maripaludis
and the mcrBDCG from M. okinawensis in M. maripaludis The His-tagged purified
rMCR then contained the M. maripaludis McrA and the M. okinawensis McrBDG. The
present study prompted us to form a working model for MCR assembly, which can be
further tested by the heterologous expression system established here.IMPORTANCE
Approximately 1.6% of the net primary production of plants, algae, and
cyanobacteria are processed by biological methane production in anoxic
environments. This accounts for about 74% of the total global methane production,
up to 25% of which is consumed by anaerobic oxidation of methane (AOM). Methyl
coenzyme M reductase (MCR) is the key enzyme in both methanogenesis and AOM. MCR
is assembled as a dimer of two heterotrimers, where posttranslational
modifications and F430 cofactors are embedded in the active sites. However, this
complex assembly process remains unknown. Here, we established a heterologous
expression system for MCR to learn how MCR is assembled.
PMID- 29339416
TI - Exploring the (Almost) Unknown: Archaeal Two-Component Systems.
AB - Two-component systems (TCS) exist in bacteria and archaea. In contrast to the
knowledge of bacterial TCSs, little information is available on their archaeal
counterparts. In the current issue of Journal of Bacteriology, Galperin and
coworkers present a bioinformatics analysis of TCS genes from archaeal genome
sequences (M. Y. Galperin, K. S. Makarova, Y. I. Wolf, and E. V. Koonin, J
Bacteriol 200:e00681-17, 2018, https://doi.org/10.1128/JB.00681-17). This study
identifies different aspects in which TCS-mediated signaling differs in bacteria
and archaea and forms a sound basis for the experimental design of studies to
increase our knowledge of this poorly investigated protein family.
PMID- 29339415
TI - Genome-Wide Identification by Transposon Insertion Sequencing of Escherichia coli
K1 Genes Essential for In Vitro Growth, Gastrointestinal Colonizing Capacity, and
Survival in Serum.
AB - Escherichia coli K1 strains are major causative agents of invasive disease of
newborn infants. The age dependency of infection can be reproduced in neonatal
rats. Colonization of the small intestine following oral administration of K1
bacteria leads rapidly to invasion of the blood circulation; bacteria that avoid
capture by the mesenteric lymphatic system and evade antibacterial mechanisms in
the blood may disseminate to cause organ-specific infections such as meningitis.
Some E. coli K1 surface constituents, in particular the polysialic acid capsule,
are known to contribute to invasive potential, but a comprehensive picture of the
factors that determine the fully virulent phenotype has not emerged so far. We
constructed a library and constituent sublibraries of ~775,000 Tn5 transposon
mutants of E. coli K1 strain A192PP and employed transposon-directed insertion
site sequencing (TraDIS) to identify genes required for fitness for infection of
2-day-old rats. Transposon insertions were lacking in 357 genes following
recovery on selective agar; these genes were considered essential for growth in
nutrient-replete medium. Colonization of the midsection of the small intestine
was facilitated by 167 E. coli K1 gene products. Restricted bacterial
translocation across epithelial barriers precluded TraDIS analysis of gut-to
blood and blood-to-brain transits; 97 genes were required for survival in human
serum. This study revealed that a large number of bacterial genes, many of which
were not previously associated with systemic E. coli K1 infection, are required
to realize full invasive potential.IMPORTANCEEscherichia coli K1 strains cause
life-threatening infections in newborn infants. They are acquired from the mother
at birth and colonize the small intestine, from where they invade the blood and
central nervous system. It is difficult to obtain information from acutely ill
patients that sheds light on physiological and bacterial factors determining
invasive disease. Key aspects of naturally occurring age-dependent human
infection can be reproduced in neonatal rats. Here, we employ transposon-directed
insertion site sequencing to identify genes essential for the in vitro growth of
E. coli K1 and genes that contribute to the colonization of susceptible rats. The
presence of bottlenecks to invasion of the blood and cerebrospinal compartments
precluded insertion site sequencing analysis, but we identified genes for
survival in serum.
PMID- 29339417
TI - Repression of VvpM Protease Expression by Quorum Sensing and the cAMP-cAMP
Receptor Protein Complex in Vibrio vulnificus.
AB - Septicemia-causing Vibrio vulnificus produces at least three exoproteases, VvpE,
VvpS, and VvpM, all of which participate in interactions with human cells.
Expression of VvpE and VvpS is induced in the stationary phase by multiple
transcription factors, including sigma factor S, SmcR, and the cAMP-cAMP receptor
protein (cAMP-CRP) complex. Distinct roles of VvpM, such as induction of
apoptosis, lead us to hypothesize VvpM expression is different from that of the
other exoproteases. Its transcription, which was found to be independent of sigma
S, is induced at the early exponential phase and then becomes negligible upon
entry into the stationary phase. SmcR and CRP were studied regarding the control
of vvpM expression. Transcription of vvpM was repressed by SmcR and cAMP-CRP
complex individually, which specifically bound to the regions -2 to +20 and +6 to
+27, respectively, relative to the vvpM transcription initiation site.
Derepression of vvpM gene expression was 10- to 40-fold greater in an smcR crp
double mutant than in single-gene mutants. Therefore, these results show that the
expression of V. vulnificus exoproteases is differentially regulated, and in this
way, distinct proteases can engage in specific interactions with a
host.IMPORTANCE An opportunistic human pathogen, Vibrio vulnificus produces
multiple extracellular proteases that are involved in diverse interactions with a
host. The total exoproteolytic activity is detected mainly in the supernatants of
the high-cell-density cultures. However, some proteolytic activity derived from a
metalloprotease, VvpM, was present in the supernatants of the low-cell-density
cultures sampled at the early growth period. In this study, we present the
regulatory mechanism for VvpM expression via repression by at least two
transcription factors. This type of transcriptional regulation is the exact
opposite of those for expression of the other V. vulnificus exoproteases.
Differential regulation of each exoprotease's production then facilitates the
pathogen's participation in the distinct interactions with a host.
PMID- 29339418
TI - An Evolutionary/Biochemical Connection Between Promoter- and Primer-Dependent
Polymerases Revealed by Selective Evolution of Ligands by Exponential Enrichment
(SELEX).
AB - DNA polymerases (DNAPs) recognize 3' recessed termini on duplex DNA and carry out
nucleotide catalysis. Unlike promoter-specific RNA polymerases (RNAPs), no
sequence specificity is required for binding or initiation of catalysis. Despite
this, previous results indicate that viral reverse transcriptases bind much more
tightly to DNA primers that mimic the polypurine tract. In the current report,
primer sequences that bind with high affinity to Taq and Klenow polymerases were
identified using a modified Selective Evolution of Ligands by Exponential
Enrichment (SELEX) approach. Two Taq-specific primers that bound ~10 (Taq1) and
over 100 (Taq2) times more stably than controls to Taq were identified. Taq1
contained 8 nucleotides (5' -CACTAAAG-3') that matched the phage T3 RNAP "core"
promoter. Both primers dramatically outcompeted primers with similar binding
thermodynamics in PCR reactions. Similarly, exonuclease minus Klenow polymerase
also selected a high affinity primer that contained a related core promoter
sequence from phage T7 RNAP (5' -ACTATAG-3'). For both Taq and Klenow, even small
modifications to the sequence resulted in large losses in binding affinity
suggesting that binding was highly sequence-specific. The results are discussed
in the context of possible effects on multi-primer (multiplex) PCR assays,
molecular information theory, and the evolution of RNAPs and DNAPs.Importance
This work further demonstrates that primer-dependent DNA polymerases can have
strong sequence biases leading to dramatically tighter binding to specific
sequences. These may be related to biological function, or be a consequences of
the structural architecture of the enzyme. New sequence specificity for Taq and
Klenow polymerases were uncovered and among them were sequences that contained
the core promoter elements from T3 and T7 phage RNA polymerase promoters. This
suggests the intriguing possibility that phage RNA polymerases exploited
intrinsic binding affinities of ancestral DNA polymerases to develop their
promotors. Conversely, DNA polymerases could have evolved from related RNA
polymerases and retained the intrinsic binding preference despite there being no
clear function for such a preference in DNA biology.
PMID- 29339419
TI - LINC00152 down-regulated miR-193a-3p to enhance MCL1 expression and promote
gastric cancer cells proliferation.
AB - The present work aimed to probe into the effect of long non-coding RNA (lncRNA)
LINC00152 on gastric cancer (GC) cells proliferation by regulating miR-193a-3p
and its target gene MCL1 Transfected si-LINC00152 was used to down-regulate
LINC00152, and cells proliferation was measured by the cell counting kit-8 (CCK
8) assay. Cell apoptosis and cell cycle were analyzed by flow cytometry (FCM).
Besides, we also detected the potential functional effects of differential
expression of LINC00152 in vivo using nude mouse xenograft model. We
overexpressed and downexpressed miR-193a-3p to study the in vitro effect of miR
193a-3p on GC cells proliferation and vitality. And MCL1 was silenced by shRNA to
investigate the effect of MCL1 on proliferation of GC cells. In this research,
LINC00152 was proven to have a higher expression level in GC tissues than in the
adjacent normal tissues. GC cells proliferation was inhibited after LINC00152 was
down-regulated. LINC00152 inhibited the expression of miR-193a-3p, which
negatively regulated MCL1 In addition, GC cells proliferation was inhibited by
cell transfection with shRNA-MCL1, and enhanced by transfection with miR-193a-3p
mimics. Our study suggested that LINC00152 was overexpressed in GC tissues, and
it down-regulated miR-193a-3p to enhance MCL1 expression thereby promoting GC
cells proliferation.
PMID- 29339420
TI - LINC00673 rs11655237 C>T confers neuroblastoma susceptibility in Chinese
population.
AB - Neuroblastoma, which accounts for approximately 10% of all pediatric cancer
related deaths, has become a therapeutic challenge and global burden attributed
to poor outcomes and mortality rates of its high-risk form. Previous genome-wide
association studies (GWASs) identified the LINC00673 rs11655237 C>T polymorphism
to be associated with the susceptibility of several malignant tumors. However,
the association between this polymorphism and neuroblastoma susceptibility is not
clear. We genotyped LINC00673 rs11655237 C>T in 393 neuroblastoma patients in
comparison with 812 age-, gender-, and ethnicity-matched healthy controls. We
found a significant association between the LINC00673 rs11655237 C>T polymorphism
and neuroblastoma risk (TT compared with CC: adjusted odds ratio (OR) =1.80, 95%
confidence interval (CI) =1.06-3.06, P=0.029; TT/CT compared with CC: adjusted OR
=1.31, 95% CI =1.02-1.67, P=0.033; and T compared with C: adjusted OR =1.29, 95%
CI =1.06-1.58, P=0.013). Furthermore, stratified analysis indicated that the
rs11655237 T allele carriers were associated with increased neuroblastoma risk
for patients with tumor originating from the adrenal gland (adjusted OR =1.51,
95% CI =1.06-2.14, P=0.021) and International Neuroblastoma Staging System (INSS)
stage IV disease (adjusted OR =1.60, 95% CI =1.12-2.30, P=0.011). In conclusion,
we verified that the LINC00673 rs11655237 C>T polymorphism might be associated
with neuroblastoma susceptibility. Prospective studies with a large sample size
and different ethnicities are needed to validate our findings.
PMID- 29339421
TI - HIF1A gene rs10873142 polymorphism is associated with risk of chronic obstructive
pulmonary disease in a Chinese Han population: a case-control study.
AB - Chronic obstructive pulmonary disease (COPD) is a type of obstructive lung
disease characterized by long-term poor airflow. Recently, variants in the
hypoxia inducible factor 1alpha (HIF1A) gene were found to be associated with
COPD risk. The present study aimed to identify whether rs10873142 polymorphism
(an intronic polymorphism) in HIF1A gene was related to COPD in a Chinese
population. We genotyped HIF1A gene rs10873142 polymorphism in a case-control
study with 235 COPD cases and 548 controls in a Chinese Han population. Odd
ratios (ORs) and 95% confidence intervals (CIs) were estimated using the chi
squared (chi2) test, genetic model analysis, and stratification analysis. In the
genetic model analysis, we found that the TT genotype (TT compared with CC: OR:
1.63; 95% CI: 1.02-2.60; P=0.042) and T allele (T compared with C: OR: 1.29;
95%CI, 1.02-1.60; P=0.032) showed significant correlation with the risk of COPD.
However, in stratification analyses of age, BMI, and forced expiratory volume in
1 s (FEV1)/FEV, we failed to find any association between HIF1A gene rs10873142
polymorphism with COPD risk. The present study supports that HIF1A gene
rs10873142 polymorphism may be associated with increased risk of COPD in a
Chinese Han population. To the best of our knowledge, this is the first case
control study uncovering that the HIF1A gene rs10873142 polymorphism increases
the risk of COPD in a Chinese Han population.
PMID- 29339422
TI - The Role of Angiopoietin-like Protein 4 in Phenylephrine-induced Cardiomyocyte
Hypertrophy.
AB - Angiopoietin-like protein 4 (ANGPTL4) is a multifunctional secreted protein that
can be induced by fasting, hypoxia and glucocorticoids. ANGPTL4 has been
associated with a variety of diseases, however, the role of ANGPTL4 in cardiac
hypertrophy remains poorly understood. In our study, we aimed to explore the
effect of ANGPTL4 on phenylephrine (PE)-induced cardiomyocyte hypertrophy. Our
results showed that knockdown of ANGPTL4 expression significantly exacerbated
cardiomyocyte hypertrophy, as demonstrated by increased hypertrophic marker
expression, including ANP and cell surface area. Moreover, significantly reduced
fatty acid oxidation, as featured by decreased CPT-1 levels, was observed in
hypertrophic cardiomyocytes following ANGPTL4 downregulation. Furthermore,
knockdown of ANGPLT4 led to downregulated expression of PPARalpha, which is the
key regulator of cardiac fatty acid oxidation. In addition, ANGPTL4 silencing
promoted the activation of JNK1/2, and JNK1/2 signaling blockade could restore
the level of PPARalpha and significantly ameliorate the ANGPTL4 knockdown-induced
cardiomyocyte hypertrophy. Therefore, our study demonstrated that ANGPTL4
regulates PPARalpha through JNK1/2 signaling and is required for the inhibition
of cardiomyocyte hypertrophy.
PMID- 29339423
TI - Immune Protection against Lethal Fungal-Bacterial Intra-Abdominal Infections.
AB - Polymicrobial intra-abdominal infections (IAIs) are clinically prevalent and
cause significant morbidity and mortality, especially those involving fungi. Our
laboratory developed a mouse model of IAI and demonstrated that intraperitoneal
inoculation with Candida albicans or other virulent non-albicans Candida (NAC)
species plus Staphylococcus aureus resulted in 70 to 80% mortality in 48 to 72 h
due to robust local and systemic inflammation (sepsis). Surprisingly, inoculation
with Candida dubliniensis or Candida glabrata with S. aureus resulted in minimal
mortality, and rechallenge of these mice with lethal C. albicans/S. aureus (i.e.,
coninfection) resulted in >90% protection. The purpose of this study was to
define requirements for C. dubliniensis/S. aureus-mediated protection and
interrogate the mechanism of the protective response. Protection was conferred by
C. dubliniensis alone or by killed C. dubliniensis plus live S. aureusS. aureus
alone was not protective, and killed S. aureus compromised C. dubliniensis
induced protection. C. dubliniensis/S. aureus also protected against lethal
challenge by NAC plus S. aureus and could protect for a long-term duration (60
days between primary challenge and C. albicans/S. aureus rechallenge).
Unexpectedly, mice deficient in T and B cells (Rag-1 knockouts [KO]) survived
both the initial C. dubliniensis/S. aureus challenge and the C. albicans/S.
aureus rechallenge, indicating that adaptive immunity did not play a role.
Similarly, mice depleted of macrophages prior to rechallenge were also protected.
In contrast, protection was associated with high numbers of Gr-1hi
polymorphonuclear leukocytes (PMNLs) in peritoneal lavage fluid within 4 h of
rechallenge, and in vivo depletion of Gr-1+ cells prior to rechallenge abrogated
protection. These results suggest that Candida species can induce protection
against a lethal C. albicans/S. aureus IAI that is mediated by PMNLs and
postulated to be a unique form of trained innate immunity.IMPORTANCE
Polymicrobial intra-abdominal infections are clinically devastating infections
with high mortality rates, particularly those involving fungal pathogens,
including Candida species. Even in patients receiving aggressive antimicrobial
therapy, mortality rates remain unacceptably high. There are no available
vaccines against IAI, which is complicated by the polymicrobial nature of the
infection. IAI leads to lethal systemic inflammation (sepsis), which is difficult
to target pharmacologically, as components of the inflammatory response are also
needed to control the infection. Our studies demonstrate that prior inoculation
with low-virulence Candida species provides strong protection against subsequent
lethal infection with C. albicans and S. aureus Surprisingly, protection is long
lived but not mediated by adaptive (specific) immunity. Instead, protection is
dependent on cells of the innate immune system (nonspecific immunity) and
provides protection against other virulent Candida species. This discovery
implies that a form of trained innate immunity may be clinically effective
against polymicrobial IAI.
PMID- 29339424
TI - Clostridium sordellii Pathogenicity Locus Plasmid pCS1-1 Encodes a Novel
Clostridial Conjugation Locus.
AB - A major virulence factor in Clostridium sordellii-mediated infection is the toxin
TcsL, which is encoded within a region of the genome called the pathogenicity
locus (PaLoc). C. sordellii isolates carry the PaLoc on the pCS1 family of
plasmids, of which there are four characterized members. Here, we determined the
potential mobility of pCS1 plasmids and characterized a fifth unique pCS1 member.
Using a derivative of the pCS1-1 plasmid from strain ATCC 9714 which had been
marked with the ermB erythromycin resistance gene, conjugative transfer into a
recipient C. sordellii isolate, R28058, was demonstrated. Bioinformatic analysis
of pCS1-1 identified a novel conjugation gene cluster defined as the C. sordellii
transfer (cst) locus. Interruption of genes within the cst locus resulted in loss
of pCS1-1 transfer, which was restored upon complementation in trans These
studies provided clear evidence that genes within the cst locus are essential for
the conjugative transfer of pCS1-1. The cst locus is present on all pCS1
subtypes, and homologous loci were identified on toxin-encoding plasmids from
Clostridium perfringens and Clostridium botulinum and also carried within genomes
of Clostridium difficile isolates, indicating that it is a widespread clostridial
conjugation locus. The results of this study have broad implications for the
dissemination of toxin genes and, potentially, antibiotic resistance genes among
members of a diverse range of clostridial pathogens, providing these
microorganisms with a survival advantage within the infected host.IMPORTANCEC.
sordellii is a bacterial pathogen that causes severe infections in humans and
animals, with high mortality rates. While the pathogenesis of C. sordellii
infections is not well understood, it is known that the toxin TcsL is an
important virulence factor. Here, we have shown the ability of a plasmid carrying
the tcsL gene to undergo conjugative transfer between distantly related strains
of C. sordellii, which has far-reaching implications for the ability of C.
sordellii to acquire the capacity to cause disease. Plasmids that carry tcsL
encode a previously uncharacterized conjugation locus, and individual genes
within this locus were shown to be required for conjugative transfer.
Furthermore, homologues on toxin plasmids from other clostridial species were
identified, indicating that this region represents a novel clostridial
conjugation locus. The results of this study have broad implications for the
dissemination of virulence genes among members of a diverse range of clostridial
pathogens.
PMID- 29339426
TI - Gut Microbial Glycerol Metabolism as an Endogenous Acrolein Source.
AB - Acrolein is a highly reactive electrophile causing toxic effects, such as DNA and
protein adduction, oxidative stress, endoplasmic reticulum stress, immune
dysfunction, and membrane damage. This Opinion/Hypothesis provides an overview of
endogenous and exogenous acrolein sources, acrolein's mode of action, and its
metabolic fate. Recent reports underpin the finding that gut microbial glycerol
metabolism leading to the formation of reuterin is an additional source of
endogenous acrolein. Reuterin is an antimicrobial multicomponent system
consisting of 3-hydroxypropionaldehyde, its dimer and hydrate, and also acrolein.
The major conclusion is that gut microbes can metabolize glycerol to reuterin and
that this transformation occurs in vivo Given the known toxicity of acrolein, the
observation that acrolein is formed in the gut necessitates further
investigations on functional relevance for gut microbiota and the host.
PMID- 29339425
TI - Secondary Metabolism and Interspecific Competition Affect Accumulation of
Spontaneous Mutants in the GacS-GacA Regulatory System in Pseudomonas protegens.
AB - Secondary metabolites are synthesized by many microorganisms and provide a
fitness benefit in the presence of competitors and predators. Secondary
metabolism also can be costly, as it shunts energy and intermediates from primary
metabolism. In Pseudomonas spp., secondary metabolism is controlled by the GacS
GacA global regulatory system. Intriguingly, spontaneous mutations in gacS or
gacA (Gac- mutants) are commonly observed in laboratory cultures. Here we
investigated the role of secondary metabolism in the accumulation of Gac- mutants
in Pseudomonas protegens strain Pf-5. Our results showed that secondary
metabolism, specifically biosynthesis of the antimicrobial compound pyoluteorin,
contributes significantly to the accumulation of Gac- mutants. Pyoluteorin
biosynthesis, which poses a metabolic burden on the producer cells, but not
pyoluteorin itself, leads to the accumulation of the spontaneous mutants.
Interspecific competition also influenced the accumulation of the Gac- mutants: a
reduced proportion of Gac- mutants accumulated when P. protegens Pf-5 was
cocultured with Bacillus subtilis than in pure cultures of strain Pf-5. Overall,
our study associated a fitness trade-off with secondary metabolism, with
metabolic costs versus competitive benefits of production influencing the
evolution of P. protegens, assessed by the accumulation of Gac-
mutants.IMPORTANCE Many microorganisms produce antibiotics, which contribute to
ecologic fitness in natural environments where microbes constantly compete for
resources with other organisms. However, biosynthesis of antibiotics is costly
due to the metabolic burdens of the antibiotic-producing microorganism. Our
results provide an example of the fitness trade-off associated with antibiotic
production. Under noncompetitive conditions, antibiotic biosynthesis led to
accumulation of spontaneous mutants lacking a master regulator of antibiotic
production. However, relatively few of these spontaneous mutants accumulated when
a competitor was present. Results from this work provide information on the
evolution of antibiotic biosynthesis and provide a framework for their discovery
and regulation.
PMID- 29339427
TI - Pandemic Paradox: Early Life H2N2 Pandemic Influenza Infection Enhanced
Susceptibility to Death during the 2009 H1N1 Pandemic.
AB - Recent outbreaks of H5, H7, and H9 influenza A viruses in humans have served as a
vivid reminder of the potentially devastating effects that a novel pandemic could
exert on the modern world. Those who have survived infections with influenza
viruses in the past have been protected from subsequent antigenically similar
pandemics through adaptive immunity. For example, during the 2009 H1N1 "swine
flu" pandemic, those exposed to H1N1 viruses that circulated between 1918 and the
1940s were at a decreased risk for mortality as a result of their previous
immunity. It is also generally thought that past exposures to antigenically
dissimilar strains of influenza virus may also be beneficial due to cross
reactive cellular immunity. However, cohorts born during prior heterosubtypic
pandemics have previously experienced elevated risk of death relative to
surrounding cohorts of the same population. Indeed, individuals born during the
1890 H3Nx pandemic experienced the highest levels of excess mortality during the
1918 "Spanish flu." Applying Serfling models to monthly mortality and influenza
circulation data between October 1997 and July 2014 in the United States and
Mexico, we show corresponding peaks in excess mortality during the 2009 H1N1
"swine flu" pandemic and during the resurgent 2013-2014 H1N1 outbreak for those
born at the time of the 1957 H2N2 "Asian flu" pandemic. We suggest that the
phenomenon observed in 1918 is not unique and points to exposure to pandemic
influenza early in life as a risk factor for mortality during subsequent
heterosubtypic pandemics.IMPORTANCE The relatively low mortality experienced by
older individuals during the 2009 H1N1 influenza virus pandemic has been well
documented. However, reported situations in which previous influenza virus
exposures have enhanced susceptibility are rare and poorly understood. One such
instance occurred in 1918-when those born during the heterosubtypic 1890 H3Nx
influenza virus pandemic experienced the highest levels of excess mortality.
Here, we demonstrate that this phenomenon was not unique to the 1918 H1N1
pandemic but that it also occurred during the contemporary 2009 H1N1 pandemic and
2013-2014 H1N1-dominated season for those born during the heterosubtypic 1957
H2N2 "Asian flu" pandemic. These data highlight the heretofore underappreciated
phenomenon that, in certain instances, prior exposure to pandemic influenza virus
strains can enhance susceptibility during subsequent pandemics. These results
have important implications for pandemic risk assessment and should inform
laboratory studies aimed at uncovering the mechanism responsible for this effect.
PMID- 29339428
TI - Mucosal Infections and Invasive Potential of Nonencapsulated Streptococcus
pneumoniae Are Enhanced by Oligopeptide Binding Proteins AliC and AliD.
AB - Nonencapsulated Streptococcus pneumoniae (NESp) is an emerging human pathogen
that colonizes the nasopharynx and is associated with noninvasive diseases such
as otitis media (OM), conjunctivitis, and nonbacteremic pneumonia. Since capsule
expression was previously thought to be necessary for establishment of invasive
pneumococcal disease (IPD), serotype-specific polysaccharide capsules are
targeted by currently licensed pneumococcal vaccines. Yet, NESp expressing
oligopeptide binding proteins AliC and AliD have been isolated during IPD. Thus,
we hypothesize AliC and AliD are major NESp virulence determinants that
facilitate persistence and development of IPD. Our study reveals that NESp
expressing AliC and AliD have intensified virulence compared to isogenic mutants.
Specifically, we demonstrate AliC and AliD enhance murine nasopharyngeal
colonization and pulmonary infection and are required for OM in a chinchilla
model. Furthermore, AliC and AliD increase pneumococcal survival in chinchilla
whole blood and aid in resistance to killing by human leukocytes. Comparative
proteome analysis revealed significant alterations in protein levels when AliC
and AliD were absent. Virulence-associated proteins, including a pneumococcal
surface protein C variant (CbpAC), were significantly downregulated, while
starvation response indicators were upregulated in the double mutant relative to
wild-type levels. We also reveal that differentially expressed CbpAC was
essential for NESp adherence to epithelial cells, virulence during OM, reduction
of C3b deposition on the NESp surface, and binding to nonspecific IgA.
Altogether, the rise in NESp prevalence urges the need to understand how NESp
establishes disease and persists in a host. This study highlights the roles of
AliC, AliD, and CbpAC in the pathogenesis of NESp.IMPORTANCE Despite the
effective, widespread use of licensed pneumococcal vaccines over many decades,
pneumococcal infections remain a worldwide burden resulting in high morbidity and
mortality. NESp subpopulations are rapidly rising in the wake of capsule-targeted
vaccine strategies, yet there is very little knowledge on NESp pathogenic
potential and virulence mechanisms. Although NESp lacks a protective capsule,
NESp lineages expressing AliC and AliD have been associated with systemic
infections. Furthermore, higher antibiotic resistance rates and transformation
efficiencies associated with emerging NESp threaten treatment strategies needed
to control pneumococcal infections and transmission. Elucidating how NESp
survives within a host and establishes disease is necessary for development of
broadened pneumococcal prevention methods. Our study identifies virulence
determinants and host survival mechanisms employed by NESp with a high pathogenic
potential. Moreover, our study also identifies virulence determinants shared by
NESp and encapsulated strains that may serve as broad prevention and therapeutic
targets.
PMID- 29339430
TI - Simultaneous Binding of Multiple EF-Tu Copies to Translating Ribosomes in Live
Escherichia coli.
AB - In bacteria, elongation factor Tu is a translational cofactor that forms ternary
complexes with aminoacyl-tRNA (aa-tRNA) and GTP. Binding of a ternary complex to
one of four flexible L7/L12 units on the ribosome tethers a charged tRNA in close
proximity to the ribosomal A site. Two sequential tests for a match between the
aa-tRNA anticodon and the current mRNA codon then follow. Because one elongation
cycle can occur in as little as 50 ms and the vast majority of aa-tRNA copies are
not cognate with the current mRNA codon, this testing must occur rapidly. We
present a single-molecule localization and tracking study of fluorescently
labeled EF-Tu in live Escherichia coli Imaging at 2 ms/frame distinguishes 60%
slowly diffusing EF-Tu copies (assigned as transiently bound to translating
ribosome) from 40% rapidly diffusing copies (assigned as a mixture of free
ternary complexes and free EF-Tu). Combining these percentages with copy number
estimates, we infer that the four L7/L12 sites are essentially saturated with
ternary complexes in vivo. The results corroborate an earlier inference that all
four sites can simultaneously tether ternary complexes near the A site, creating
a high local concentration that may greatly enhance the rate of testing of aa
tRNAs. Our data and a combinatorial argument both suggest that the initial
recognition test for a codon-anticodon match occurs in less than 1 to 2 ms per aa
tRNA copy. The results refute a recent study (A. Plochowietz, I. Farrell, Z.
Smilansky, B. S. Cooperman, and A. N. Kapanidis, Nucleic Acids Res 45:926-937,
2016, https://doi.org/10.1093/nar/gkw787) of tRNA diffusion in E. coli that
inferred that aa-tRNAs arrive at the ribosomal A site as bare monomers, not as
ternary complexes.IMPORTANCE Ribosomes catalyze translation of the mRNA codon
sequence into the corresponding sequence of amino acids within the nascent
polypeptide chain. Polypeptide elongation can be as fast as 50 ms per added amino
acid. Each amino acid arrives at the ribosome as a ternary complex comprising an
aminoacyl-tRNA (aa-tRNA), an elongation factor called EF-Tu, and GTP. There are
43 different aa-tRNAs in use, only one of which typically matches the current
mRNA codon. Thus, ternary complexes must be tested very rapidly. Here we use
fluorescence-based single-molecule methods that locate and track single EF-Tu
copies in E. coli Fast and slow diffusive behavior determines the fraction of EF
Tu copies that are ribosome bound. We infer simultaneous tethering of ~4 ternary
complexes to the ribosome, which may facilitate rapid initial testing for codon
matching on a time scale of less than 1 to 2 ms per aa-tRNA.
PMID- 29339429
TI - The Biochemistry of Sensing: Enteric Pathogens Regulate Type III Secretion in
Response to Environmental and Host Cues.
AB - Enteric pathogens employ sophisticated strategies to colonize and infect
mammalian hosts. Gram-negative bacteria, such as Escherichia coli, Salmonella,
and Campylobacter jejuni, are among the leading causes of gastrointestinal tract
infections worldwide. The virulence strategies of many of these Gram-negative
pathogens rely on type III secretion systems (T3SSs), which are macromolecular
syringes that translocate bacterial effector proteins directly into the host
cytosol. However, synthesis of T3SS proteins comes at a cost to the bacterium in
terms of growth rate and fitness, both in the environment and within the host.
Therefore, expression of the T3SS must be tightly regulated to occur at the
appropriate time and place during infection. Enteric pathogens have thus evolved
regulatory mechanisms to control expression of their T3SSs in response to
specific environmental and host cues. These regulatory cascades integrate
multiple physical and chemical signals through complex transcriptional networks.
Although the power of bacterial genetics has allowed elucidation of many of these
networks, the biochemical interactions between signal and sensor that initiate
the signaling cascade are often poorly understood. Here, we review the physical
and chemical signals that Gram-negative enteric pathogens use to regulate T3SS
expression during infection. We highlight the recent structural and functional
studies that have elucidated the biochemical properties governing both the
interaction between sensor and signal and the mechanisms of signal transduction
from sensor to downstream transcriptional networks.
PMID- 29339431
TI - Molecular Insights into Function and Competitive Inhibition of Pseudomonas
aeruginosa Multiple Virulence Factor Regulator.
AB - New approaches to antimicrobial drug discovery are urgently needed to combat
intractable infections caused by multidrug-resistant (MDR) bacteria. Multiple
virulence factor regulator (MvfR or PqsR), a Pseudomonas aeruginosa quorum
sensing transcription factor, regulates functions important in both acute and
persistent infections. Recently identified non-ligand-based benzamine
benzimidazole (BB) inhibitors of MvfR suppress both acute and persistent P.
aeruginosa infections in mice without perturbing bacterial growth. Here, we
elucidate the crystal structure of the MvfR ligand binding domain (LBD) in
complex with one potent BB inhibitor, M64. Structural analysis indicated that M64
binds, like native ligands, to the MvfR hydrophobic cavity. A hydrogen bond and
pi interaction were found to be important for MvfR-M64 affinity. Surface plasmon
resonance analysis demonstrated that M64 is a competitive inhibitor of MvfR.
Moreover, a protein engineering approach revealed that Gln194 and Tyr258 are
critical for the interaction between MvfR and M64. Random mutagenesis of the full
length MvfR protein identified a single-amino-acid substitution, I68F, at a DNA
binding linker domain that confers M64 insensitivity. In the presence of M64,
I68F but not the wild-type (WT) MvfR protein retained DNA binding ability. Our
findings strongly suggest that M64 promotes conformational change at the DNA
binding domain of MvfR and that the I68F mutation may compensate for this change,
indicating allosteric inhibition. This work provides critical new insights into
the molecular mechanism of MvfR function and inhibition that could aid in the
optimization of anti-MvfR compounds and improve our understanding of MvfR
regulation.IMPORTANCEPseudomonas aeruginosa is an opportunistic Gram-negative
pathogen that causes serious acute, persistent, and relapsing infections. New
approaches to antimicrobial drug discovery are urgently needed to combat
intractable infections caused by this pathogen. The Pseudomonas aeruginosa quorum
sensing transcription factor MvfR regulates functions important in both acute and
persistent infections. We used recently identified inhibitors of MvfR to perform
structural studies and reveal important insights that would benefit the
optimization of anti-MvfR compounds. Altogether, the results reported here
provide critical detailed mechanistic insights into the function of MvfR domains
that may benefit the optimization of the chemical, pharmacological, and safety
properties of MvfR antagonist series.
PMID- 29339432
TI - Deregulation of HDAC5 by Viral Interferon Regulatory Factor 3 Plays an Essential
Role in Kaposi's Sarcoma-Associated Herpesvirus-Induced Lymphangiogenesis.
AB - Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent for
Kaposi's sarcoma (KS), which is one of the most common HIV-associated neoplasms.
The endothelium is the thin layer of squamous cells where vascular blood
endothelial cells (BECs) line the interior surface of blood vessels and lymphatic
endothelial cells (LECs) are in direct contact with lymphatic vessels. The KS
lesions contain a prominent compartment of neoplastic spindle morphology cells
that are closely related to LECs. Furthermore, while KSHV can infect both LECs
and BECs in vitro, its infection activates genetic programming related to
lymphatic endothelial cell fate, suggesting that lymphangiogenic pathways are
involved in KSHV infection and malignancy. Here, we report for the first time
that viral interferon regulatory factor 3 (vIRF3) is readily detected in over 40%
of KS lesions and that vIRF3 functions as a proangiogenic factor, inducing
hypersprouting formation and abnormal growth in a LEC-specific manner. Mass
spectrometry analysis revealed that vIRF3 interacted with histone deacetylase 5
(HDAC5), which is a signal-responsive regulator for vascular homeostasis. This
interaction blocked the phosphorylation-dependent cytosolic translocation of
HDAC5 and ultimately altered global gene expression in LECs but not in BECs.
Consequently, vIRF3 robustly induced spindle morphology and hypersprouting
formation of LECs but not BECs. Finally, KSHV infection led to the hypersprouting
formation of LECs, whereas infection with a DeltavIRF3 mutant did not do so.
Collectively, our data indicate that vIRF3 alters global gene expression and
induces a hypersprouting formation in an HDAC5-binding-dependent and LEC-specific
manner, ultimately contributing to KSHV-associated pathogenesis.IMPORTANCE
Several lines of evidences indicate that KSHV infection of LECs induces
pathological lymphangiogenesis and that the results resemble KS-like spindle
morphology. However, the underlying molecular mechanism remains unclear. Here, we
demonstrated that KSHV vIRF3 is readily detected in over 40% of various KS
lesions and functions as a potent prolymphangiogenic factor by blocking the
phosphorylation-dependent cytosolic translocation of HDAC5, which in turn
modulates global gene expression in LECs. Consequently, vIRF3-HDAC5 interaction
contributes to virus-induced lymphangiogenesis. The results of this study suggest
that KSHV vIRF3 plays a crucial role in KSHV-induced malignancy.
PMID- 29339433
TI - Five-Year Mortality After Transient Ischemic Attack: Focus on Cardiometabolic
Comorbidity and Hospital Readmission.
AB - BACKGROUND AND PURPOSE: We aimed at providing estimates of mortality associated
with cardiometabolic comorbidity and incident readmission from cardiometabolic as
compared with noncardiometabolic conditions after a first transient ischemic
attack. METHODS: Between 2000 and 2015, patients hospitalized for a first
transient ischemic attack were examined for cardiometabolic comorbidities
(diabetes mellitus, coronary artery disease, heart failure, and atrial
fibrillation), 5-year incident hospitalization, and time to death. RESULTS: Of
251 patients with transient ischemic attack, 134 (53%) had at least 1 and 55
(22%) had at least 2 cardiometabolic conditions. By 5 years, 491 readmissions
(134 [27%] cardiometabolic and 357 [73%] noncardiometabolic) and 75 deaths (27
[36%] cardiometabolic and 47 [64%] noncardiometabolic) were observed. Mortality
was increased with any concurrent cardiometabolic comorbidity (hazard ratio,
1.89; 95% confidence interval, 1.17-3.03; P=0.0089) with multiplicative mortality
risk from a combination of coronary artery disease and heart failure. Each
hospitalization was associated with a 1.5-fold risk of death (95% confidence
interval, 1.37-1.64; P<0.0001). Risk of cardiometabolic and noncardiometabolic
mortality was correlated with the corresponding category-specific readmission.
CONCLUSIONS: Among patients hospitalized for first transient ischemic attack, 5
year mortality is associated with concurrent cardiometabolic comorbidity and
rates of subsequent hospitalization.
PMID- 29339434
TI - Cerebrovascular Outcomes With Proton Pump Inhibitors and Thienopyridines: A
Systematic Review and Meta-Analysis.
AB - BACKGROUND AND PURPOSE: Pharmacokinetic and prior studies on thienopyridine and
proton pump inhibitors (PPI) coadministration provide conflicting data for
cardiovascular outcomes, whereas there is no established evidence on the
association of concomitant use of PPI and thienopyridines with adverse
cerebrovascular outcomes. METHODS: We conducted a systematic review and meta
analysis of randomized controlled trials and cohort studies from inception to
July 2017, reporting following outcomes among patients treated with
thienopyridine and PPI versus thienopyridine alone (1) ischemic stroke, (2)
combined ischemic or hemorrhagic stroke, (3) composite outcome of stroke,
myocardial infarction (MI), and cardiovascular death, (4) MI, (5) all-cause
mortality, and (6) major or minor bleeding events. After the unadjusted analyses
of risk ratios, we performed additional analyses of studies reporting hazard
ratios adjusted for potential confounders. RESULTS: We identified 22 studies (12
randomized controlled trials and 10 cohort studies) comprising 131 714 patients.
Concomitant use of PPI with thienopyridines was associated with increased risk of
ischemic stroke (risk ratio, 1.74; 95% confidence interval [CI], 1.41-2.16;
P<0.001), composite stroke/MI/cardiovascular death (risk ratio, 1.14; 95% CI,
1.01-1.29; P=0.04), and MI (risk ratio, 1.19; 95% CI, 1.00-1.40; P=0.05).
Likewise, in adjusted analyses concomitant use of PPI with thienopyridines was
again associated with increased risk of stroke (hazard ratios adjusted, 1.30; 95%
CI, 1.04-1.61; P=0.02), composite stroke/MI/cardiovascular death (hazard ratios
adjusted, 1.23; 95% CI, 1.03-1.47; P=0.02), but not with MI (hazard ratios
adjusted, 1.19; 95% CI, 0.93-1.52; P=0.16). CONCLUSIONS: Co-prescription of PPI
and thienopyridines increases the risk of incident ischemic strokes and composite
stroke/MI/cardiovascular death. Our findings corroborate the current guidelines
for PPI deprescription and pharmacovigilance, especially in patients treated with
thienopyridines.
PMID- 29339436
TI - Rewired Notch/p53 by Numb'ing Mdm2.
AB - Although numerous pathways are known to control the tumor suppressor protein p53,
coordinated regulation of the p53-Notch axis by Numb may have an even more
remarkable impact. In this issue, Colaluca at al. (2018. J. Cell Biol.
https://doi.org/10.1083/jcb.201709092) reveal an unexpected role of a newly
characterized Numb splice variant in the regulation of p53, which may have
significant implications for therapeutic intervention in breast cancer.
PMID- 29339435
TI - Corrected and Republished from: The COP9 Signalosome Interacts with and Regulates
Interferon Regulatory Factor 5 Protein Stability.
AB - The transcription factor interferon regulatory factor 5 (IRF5) exerts crucial
functions in the regulation of host immunity against extracellular pathogens, DNA
damage-induced apoptosis, death receptor signaling, and macrophage polarization.
Tight regulation of IRF5 is thus warranted for an efficient response to
extracellular stressors and for limiting autoimmune and inflammatory responses.
Here we report that the COP9 signalosome (CSN), a general modulator of diverse
cellular and developmental processes, associates constitutively with IRF5 and
promotes its protein stability. The constitutive CSN/IRF5 interaction was
identified using proteomics and confirmed by endogenous immunoprecipitations. The
CSN/IRF5 interaction occurred on the carboxyl and amino termini of IRF5; a single
internal deletion (Delta455-466) was found to significantly reduce IRF5 protein
stability. CSN3 was identified as a direct interacting partner of IRF5, and
knockdown of this subunit with small interfering RNAs (siRNAs) resulted in
enhanced degradation. Degradation was further augmented by knockdown of CSN1 and
CSN3 together. The ubiquitin E1 inhibitor UBEI-41 or the proteasome inhibitor
MG132 prevented IRF5 degradation, supporting that its stability is regulated by
the ubiquitin-proteasome system. Importantly, activation of IRF5 by the death
receptor ligand tumor necrosis factor (TNF)-related apoptosis-inducing ligand
(TRAIL) resulted in enhanced degradation via loss of the CSN/IRF5 interaction.
This study defines the CSN as a new interacting partner of IRF5 that controls its
stability.
PMID- 29339437
TI - SPR2 protects minus ends to promote severing and reorientation of plant cortical
microtubule arrays.
AB - The cortical microtubule arrays of higher plants are organized without
centrosomes and feature treadmilling polymers that are dynamic at both ends. The
control of polymer end stability is fundamental for the assembly and organization
of cytoskeletal arrays, yet relatively little is understood about how microtubule
minus ends are controlled in acentrosomal microtubule arrays, and no factors have
been identified that act at the treadmilling minus ends in higher plants. Here,
we identify Arabidopsis thaliana SPIRAL2 (SPR2) as a protein that tracks minus
ends and protects them against subunit loss. SPR2 function is required to
facilitate the rapid reorientation of plant cortical arrays as stimulated by
light perception, a process that is driven by microtubule severing to create a
new population of microtubules. Quantitative live-cell imaging and computer
simulations reveal that minus protection by SPR2 acts by an unexpected mechanism
to promote the lifetime of potential SPR2 severing sites, increasing the
likelihood of severing and thus the rapid amplification of the new microtubule
array.
PMID- 29339438
TI - Quantifying exosome secretion from single cells reveals a modulatory role for
GPCR signaling.
AB - Exosomes are small endosome-derived extracellular vesicles implicated in cell
cell communication and are secreted by living cells when multivesicular bodies
(MVBs) fuse with the plasma membrane (PM). Current techniques to study exosome
physiology are based on isolation procedures after secretion, precluding direct
and dynamic insight into the mechanics of exosome biogenesis and the regulation
of their release. In this study, we propose real-time visualization of MVB-PM
fusion to overcome these limitations. We designed tetraspanin-based pH-sensitive
optical reporters that detect MVB-PM fusion using live total internal reflection
fluorescence and dynamic correlative light-electron microscopy. Quantitative
analysis demonstrates that MVB-PM fusion frequency is reduced by depleting the
target membrane SNAREs SNAP23 and syntaxin-4 but also can be induced in single
cells by stimulation of the histamine H1 receptor (H1HR). Interestingly,
activation of H1R1 in HeLa cells increases Ser110 phosphorylation of SNAP23,
promoting MVB-PM fusion and the release of CD63-enriched exosomes. Using this
single-cell resolution approach, we highlight the modulatory dynamics of MVB
exocytosis that will help to increase our understanding of exosome physiology and
identify druggable targets in exosome-associated pathologies.
PMID- 29339439
TI - IDH1/2 Mutations Sensitize Acute Myeloid Leukemia to PARP Inhibition and This Is
Reversed by IDH1/2-Mutant Inhibitors.
AB - Purpose: Somatic mutations in IDH1/2 occur in approximately 20% of patients with
myeloid neoplasms, including acute myeloid leukemia (AML). IDH1/2MUT enzymes
produce D-2-hydroxyglutarate (D2HG), which associates with increased DNA damage
and improved responses to chemo/radiotherapy and PARP inhibitors in solid tumor
cells. Whether this also holds true for IDH1/2MUT AML is not known.Experimental
Design: Well-characterized primary IDH1MUT, IDH2MUT, and IDH1/2WT AML cells were
analyzed for DNA damage and responses to daunorubicin, ionizing radiation, and
PARP inhibitors.Results:IDH1/2MUT caused increased DNA damage and sensitization
to daunorubicin, irradiation, and the PARP inhibitors olaparib and talazoparib in
AML cells. IDH1/2MUT inhibitors protected against these treatments. Combined
treatment with a PARP inhibitor and daunorubicin had an additive effect on the
killing of IDH1/2MUT AML cells. We provide evidence that the therapy sensitivity
of IDH1/2MUT cells was caused by D2HG-mediated downregulation of expression of
the DNA damage response gene ATM and not by altered redox responses due to
metabolic alterations in IDH1/2MUT cells.Conclusions:IDH1/2MUT AML cells are
sensitive to PARP inhibitors as monotherapy but especially when combined with a
DNA-damaging agent, such as daunorubicin, whereas concomitant administration of
IDH1/2MUT inhibitors during cytotoxic therapy decrease the efficacy of both
agents in IDH1/2MUT AML. These results advocate in favor of clinical trials of
PARP inhibitors either or not in combination with daunorubicin in IDH1/2MUT AML.
Clin Cancer Res; 24(7); 1705-15. (c)2018 AACR.
PMID- 29339441
TI - Allele-Specific Droplet Digital PCR Combined with a Next-Generation Sequencing
Based Algorithm for Diagnostic Copy Number Analysis in Genes with High Homology:
Proof of Concept Using Stereocilin.
AB - BACKGROUND: Copy number variants (CNVs) can substantially contribute to the
pathogenic variant spectrum in several disease genes. The detection of this type
of variant is complicated in genes with high homology to other genomic sequences,
yet such genomics regions are more likely to lead to CNVs, making it critical to
address detection in these settings. METHODS: We developed a copy number analysis
approach for high homology genes/regions that consisted of next-generation
sequencing (NGS)-based dosage analysis accompanied by allele-specific droplet
digital PCR (ddPCR) confirmatory testing. We applied this approach to copy number
analysis in STRC, a gene with 98.9% homology to a nonfunctional pseudogene,
pSTRC, and characterized its accuracy in detecting different copy number states
by use of known samples. RESULTS: Using a cohort of 517 patients with hearing
loss, we prospectively demonstrated the clinical utility of the approach, which
contributed 30 of the 122 total positives (6%) to the diagnostic yield,
increasing the overall yield from 17.6% to 23.6%. Positive STRC genotypes
included homozygous (n = 15) or compound heterozygous (n = 8) deletions, or
heterozygous deletions in trans with pathogenic sequence variants (n = 7).
Finally, this approach limited ddPCR testing to cases with NGS copy number
findings, thus markedly reducing the number of costly and laborious, albeit
specific, ddPCR tests. CONCLUSIONS: NGS-based CNV detection followed by allele
specific ddPCR confirmatory testing is a reliable and affordable approach for
copy number analysis in medically relevant genes with homology issues.
PMID- 29339440
TI - Repurposing Tin Mesoporphyrin as an Immune Checkpoint Inhibitor Shows Therapeutic
Efficacy in Preclinical Models of Cancer.
AB - Purpose: Unprecedented clinical outcomes have been achieved in a variety of
cancers by targeting immune checkpoint molecules. This preclinical study
investigates heme oxygenase-1 (HO-1), an immunosuppressive enzyme that is
expressed in a wide variety of cancers, as a potential immune checkpoint target
in the context of a chemotherapy-elicited antitumor immune response. We evaluate
repurposing tin mesoporphyrin (SnMP), which has demonstrated safety and efficacy
targeting hepatic HO in the clinic for the treatment of hyperbilirubinemia, as an
immune checkpoint blockade therapy for the treatment of cancer.Experimental
Design: SnMP and genetic inactivation of myeloid HO-1 were evaluated alongside 5
fluorouracil in an aggressive spontaneous murine model of breast cancer (MMTV
PyMT). Single-cell RNA sequencing analysis, tumor microarray, and clinical
survival data from breast cancer patients were used to support the clinical
relevance of our observations.Results: We demonstrate that SnMP inhibits immune
suppression of chemotherapy-elicited CD8+ T cells by targeting myeloid HO-1
activity in the tumor microenvironment. Microarray and survival data from breast
cancer patients reveal that HO-1 is a poor prognostic factor in patients
receiving chemotherapy. Single-cell RNA-sequencing analysis suggests that the
myeloid lineage is a significant source of HO-1 expression, and is co-expressed
with the immune checkpoints PD-L1/2 in human breast tumors. In vivo, we
therapeutically compare the efficacy of targeting these two pathways alongside
immune-stimulating chemotherapy, and demonstrate that the efficacy of SnMP
compares favorably with PD-1 blockade in preclinical models.Conclusions: SnMP
could represent a novel immune checkpoint therapy, which may improve the
immunological response to chemotherapy. Clin Cancer Res; 24(7); 1617-28. (c)2018
AACR.
PMID- 29339442
TI - Specific Substrate for the Assay of Lysosomal Acid Lipase.
AB - BACKGROUND: Deficiency of lysosomal acid lipase (LAL) causes Wolman disease and
cholesterol ester storage disease. With the recent introduction of enzyme
replacement therapy to manage LAL deficiency comes the need for a reliable assay
of LAL enzymatic activity that can be applied to dried blood spots (DBS).
METHODS: We prepared and tested a library of analogs of palmitoyl 4
methylumbelifferyl esters to find a highly active and specific substrate for LAL
in DBS. The LAL assay was optimized leading to both LC-MS/MS and fluorometric
assay of LAL. We tested the new assay on DBS from healthy and LAL-deficient
patients. RESULTS: The ester formed between palmitic acid and 4-propyl-8-methyl-7
hydroxycoumarin (P-PMHC) was found to be >98% selective for LAL in DBS based on
the sensitivity of its activity to the LAL-specific inactivator Lalistat-2 and
the fact that the activity was close to zero using DBS from patients previously
shown to be LAL-deficient. Use of P-PMHC and heavy isotope-labeled internal
standard with optimized assay conditions led to an approximately 2-fold increase
in the specific activity of LAL compared with the previously reported LAL assay.
Patients deficient in LAL were readily distinguished from normal persons with the
new LAL assay using UPLC-MS/MS or fluorometric assay platforms. CONCLUSIONS: The
new assay can measure LAL in DBS with a single measurement compared with the
previous method involving 2 assays done in parallel.
PMID- 29339443
TI - Immune system: The "seventh sense".
AB - The brain is our computing machine that integrates stimuli from the environment
and orchestrates responses to these stimuli. Here, I propose that the defining
role of the immune system is to sense microorganisms and to inform the brain
about them.
PMID- 29339444
TI - LIGHT-HVEM signaling in keratinocytes controls development of dermatitis.
AB - Dermatitis is often associated with an allergic reaction characterized by
excessive type 2 responses leading to epidermal acanthosis, hyperkeratosis, and
dermal inflammation. Although factors like IL-4, IL-13, and thymic stromal
lymphopoietin (TSLP) are thought to be instrumental for the development of this
type of skin disorder, other cytokines may be critical. Here, we show that the
tumor necrosis factor (TNF) superfamily protein LIGHT (homologous to lymphotoxin,
exhibits inducible expression, and competes with HSV glycoprotein D for binding
to HVEM, a receptor expressed on T lymphocytes) is required for experimental
atopic dermatitis, and LIGHT directly controls keratinocyte hyperplasia, and
production of periostin, a matricellular protein that contributes to the clinical
features of atopic dermatitis as well as other skin diseases such as scleroderma.
Mice with a conditional deletion of the LIGHT receptor HVEM (herpesvirus entry
mediator) in keratinocytes phenocopied LIGHT-deficient mice in exhibiting reduced
epidermal thickening and dermal collagen deposition in a model of atopic
dermatitis driven by house dust mite allergen. LIGHT signaling through HVEM in
human epidermal keratinocytes directly induced proliferation and periostin
expression, and both keratinocyte-specific deletion of HVEM or antibody blocking
of LIGHT-HVEM interactions after disease onset prevented expression of periostin
and limited atopic dermatitis symptoms. Developing reagents that neutralize LIGHT
HVEM signaling might be useful for therapeutic intervention in skin diseases
where periostin is a central feature.
PMID- 29339445
TI - Bile acids in glucose metabolism in health and disease.
AB - Bile acids (BAs) are cholesterol-derived metabolites that facilitate the
intestinal absorption and transport of dietary lipids. Recently, BAs also emerged
as pivotal signaling molecules controlling glucose, lipid, and energy metabolism
by binding to the nuclear hormone farnesoid X receptor (FXR) and Takeda G protein
receptor 5 (TGR5) in multiple organs, leading to regulation of intestinal
incretin secretion, hepatic gluconeogenesis, glycogen synthesis, energy
expenditure, inflammation, and gut microbiome configuration. Alterations in BA
metabolism and signaling are associated with obesity and type 2 diabetes mellitus
(T2DM), whereas treatment of T2DM patients with BA sequestrants, or bariatric
surgery in morbidly obese patients, results in a significant improvement in
glycemic response that is associated with changes in the BA profile and
signaling. Herein, we review the roles of BAs in glucose metabolism in health and
disease; highlight the limitations, unknowns, and challenges in understanding the
impact of BAs on the glycemic response; and discuss how this knowledge may be
harnessed to develop innovative therapeutic approaches for the treatment of
hyperglycemia and diabetes.
PMID- 29339446
TI - Ontogeny of human mucosal-associated invariant T cells and related T cell
subsets.
AB - Mucosal-associated invariant T (MAIT) cells are semi-invariant Valpha7.2+
CD161highCD4- T cells that recognize microbial riboflavin precursor derivatives
such as 5-OP-RU presented by MR1. Human MAIT cells are abundant in adult blood,
but there are very few in cord blood. We longitudinally studied Valpha7.2+
CD161high T cell and related subset levels in infancy and after cord blood
transplantation. We show that Valpha7.2+ and Valpha7.2- CD161high T cells are
generated early during gestation and likely share a common prenatal developmental
program. Among cord blood Valpha7.2+ CD161high T cells, the minority recognizing
MR1:5-OP-RU display a TRAV/TRBV repertoire very similar to adult MAIT cells.
Within a few weeks of life, only the MR1:5-OP-RU reactive Valpha7.2+ CD161high T
cells acquire a memory phenotype. Only these cells expand to form the adult MAIT
pool, diluting out other Valpha7.2+ CD161high and Valpha7.2- CD161high
populations, in a process requiring at least 6 years to reach adult levels. Thus,
the high clonal size of adult MAIT cells is antigen-driven and likely due to the
fine specificity of the TCRalphabeta chains recognizing MR1-restricted microbial
antigens.
PMID- 29339447
TI - Guidance of super-enhancers in regulation of IL-9 induction and airway
inflammation.
AB - Th9 cells are prominently featured in allergic lung inflammation, but the
mechanism that regulates IL-9 induction in T helper cells remains poorly defined.
Here we demonstrate that formation of super-enhancers (SEs) is critical in robust
induction of IL-9 and that assembly of the Il9 SEs in Th cells requires OX40
triggered chromatin acetylation. Mechanistically, we found that OX40
costimulation induces RelB expression, which recruits the histone
acetyltransferase p300 to the Il9 locus to catalyze H3K27 acetylation. This
allows binding of the SE factor Brd4 to organize assembly of the SE complex,
which in turn drives robust IL-9 expression and Th9 cell induction. Thus, Th9
cells are strongly induced upon OX40 stimulation, and disruption of SEs abolished
Th9 cell induction in vitro and inhibited Th9 cell-mediated allergic airway
inflammation in vivo. Together, our data suggest that formation of SEs is
essential in IL-9 expression and Th9 cell induction. These findings may have
important clinical implications.
PMID- 29339448
TI - Development of intestinal M cells and follicle-associated epithelium is regulated
by TRAF6-mediated NF-kappaB signaling.
AB - M cells are located in the follicle-associated epithelium (FAE) that covers
Peyer's patches (PPs) and are responsible for the uptake of intestinal antigens.
The differentiation of M cells is initiated by receptor activator of NF-kappaB.
However, the intracellular pathways involved in M cell differentiation are still
elusive. In this study, we demonstrate that the NF-kappaB pathway activated by
RANK is essential for M cell differentiation using in vitro organoid culture.
Overexpression of NF-kappaB transcription factors enhances the expression of M
cell-associated molecules but is not sufficient to complete M cell
differentiation. Furthermore, we evaluated the requirement for tumor necrosis
factor receptor-associated factor 6 (TRAF6). Conditional deletion of TRAF6 in the
intestinal epithelium causes a complete loss of M cells in PPs, resulting in
impaired antigen uptake into PPs. In addition, the expression of FAE-associated
genes is almost silenced in TRAF6-deficient mice. This study thus demonstrates
the crucial role of TRAF6-mediated NF-kappaB signaling in the development of M
cells and FAE.
PMID- 29339449
TI - Targeting IRF3 as a YAP agonist therapy against gastric cancer.
AB - The Hippo pathway plays a vital role in tissue homeostasis and tumorigenesis. The
transcription factor IRF3 is essential for innate antiviral immunity. In this
study, we discovered IRF3 as an agonist of Yes-associated protein (YAP). The
expression of IRF3 is positively correlated with that of YAP and its target genes
in gastric cancer; the expression of both IRF3 and YAP is up-regulated and
prognosticates patient survival. IRF3 interacts with both YAP and TEAD4 in the
nucleus to enhance their interaction, promoting nuclear translocation and
activation of YAP. IRF3 and YAP-TEAD4 are associated genome-wide to cobind and
coregulate many target genes of the Hippo pathway. Overexpression of active IRF3
increased, but depletion of IRF3 reduced, the occupancy of YAP on the target
genes. Knockdown or pharmacological targeting of IRF3 by Amlexanox, a drug used
clinically for antiinflammatory treatment, inhibits gastric tumor growth in a YAP
dependent manner. Collectively, our study identifies IRF3 as a positive regulator
for YAP, highlighting a new therapeutic target against YAP-driven cancers.
PMID- 29339451
TI - Inhibition of 5alpha-reductase alters pregnane metabolism in the late pregnant
mare.
AB - In the latter half of gestation in the mare, progesterone concentrations decline
to near undetectable levels while other 5alpha-reduced pregnanes are elevated. Of
these, 5alpha-dihydroprogesterone and allopregnanolone have been reported to have
important roles in either pregnancy maintenance or fetal quiescence. During this
time, the placenta is necessary for pregnane metabolism, with the enzyme 5alpha
reductase being required for the conversion of progesterone to 5alpha
dihydroprogesterone. The objectives of this study were to assess the effects of a
5alpha-reductase inhibitor, dutasteride on pregnane metabolism (pregnenolone,
progesterone, 5alpha-dihydroprogesterone, 20alpha-hydroxy-5alpha-pregnan-3-one,
5alpha-pregnane-3beta,20alpha-diol and allopregnanolone), to determine
circulating dutasteride concentrations and to assess effects of dutasteride
treatment on gestational parameters. Pregnant mares (n = 5) received dutasteride
(0.01 mg/kg/day, IM) and control mares (n = 4) received vehicle alone from 300 to
320 days of gestation or until parturition. Concentrations of dutasteride,
pregnenolone, progesterone, 5alpha-dihydroprogesterone, 20alpha-hydroxy-5alpha
pregnan-3-one, 5alpha-pregnane-3beta,20alpha-diol, and allopregnanolone were
evaluated via liquid chromatography-tandem mass spectrometry. Samples were
analyzed as both days post treatment and as days prepartum. No significant
treatment effects were detected in pregnenolone, 5alpha-dihydroprogesterone,
20alpha-hydroxy-5alpha-pregnan-3-one, 5alpha-pregnane-3beta,20alpha-diol or
allopregnanolone for either analysis; however, progesterone concentrations were
increased (P < 0.05) sixfold in dutasteride-treated mares compared to control
mares. Dutasteride concentrations increased in the treated mares, with a
significant correlation (P < 0.05) between dutasteride concentrations and
pregnenolone or progesterone concentrations. Gestational length and neonatal
outcomes were not significantly altered in dutasteride-treated mares. Although
5alpha-reduced metabolites were unchanged, these data suggest an accumulation of
precursor progesterone with inhibition of 5alpha-reductase, indicating the
ability of dutasteride to alter progesterone metabolism.
PMID- 29339450
TI - Cardiac macrophages promote diastolic dysfunction.
AB - Macrophages populate the healthy myocardium and, depending on their phenotype,
may contribute to tissue homeostasis or disease. Their origin and role in
diastolic dysfunction, a hallmark of cardiac aging and heart failure with
preserved ejection fraction, remain unclear. Here we show that cardiac
macrophages expand in humans and mice with diastolic dysfunction, which in mice
was induced by either hypertension or advanced age. A higher murine myocardial
macrophage density results from monocyte recruitment and increased hematopoiesis
in bone marrow and spleen. In humans, we observed a parallel constellation of
hematopoietic activation: circulating myeloid cells are more frequent, and
splenic 18F-FDG PET/CT imaging signal correlates with echocardiographic indices
of diastolic dysfunction. While diastolic dysfunction develops, cardiac
macrophages produce IL-10, activate fibroblasts, and stimulate collagen
deposition, leading to impaired myocardial relaxation and increased myocardial
stiffness. Deletion of IL-10 in macrophages improves diastolic function. These
data imply expansion and phenotypic changes of cardiac macrophages as therapeutic
targets for cardiac fibrosis leading to diastolic dysfunction.
PMID- 29339452
TI - Effects of colostrum, feeding method and oral IGF1 on porcine uterine
development.
AB - Nursing ensures lactocrine delivery of maternally derived, milk-borne bioactive
factors to offspring, which affects postnatal development of female reproductive
tract tissues. Disruption of lactocrine communication for two days from birth
(postnatal day (PND) 0) by feeding milk replacer in lieu of nursing or
consumption of colostrum alters porcine uterine gene expression globally by PND 2
and inhibits uterine gland genesis by PND 14. Here, objectives were to determine
effects of: (1) nursing or milk replacer feeding from birth; (2) a single dose of
colostrum or milk replacer and method of feeding and (3) a single feeding of
colostrum or milk replacer, with or without oral supplementation of IGF1,
administered at birth on aspects of porcine uterine development at 12-h
postnatally. Results indicate nursing for 12 h from birth supports rapid
establishment of a uterine developmental program, illustrated by patterns of
endometrial cell proliferation, expression of genes associated with uterine wall
development and entry into mitosis and establishment of a uterine MMP9/TIMP1
system. A single feeding of colostrum at birth increased endometrial cell
proliferation at 12 h, regardless of method of feeding. Oral supplementation of
IGF1 was sufficient to support endometrial cell proliferation at 12 h in replacer
fed gilts, and supplementation of colostrum with IGF1 further increased
endometrial cell proliferation. Results indicate that lactocrine regulation of
postnatal uterine development is initiated with the first ingestion of colostrum.
Further, results suggest IGF1 may be lactocrine-active and support a 12-h
bioassay, which can be used to identify uterotrophic lactocrine activity.
PMID- 29339453
TI - PGRMC1 localization and putative function in the nucleolus of bovine granulosa
cells and oocytes.
AB - Progesterone receptor membrane component-1 (PGRMC1) is a highly conserved
multifunctional protein that is found in numerous systems, including reproductive
system. Interestingly, PGRMC1 is expressed at several intracellular locations,
including the nucleolus. The aim of this study is to investigate the functional
relationship between PGRMC1 and nucleolus. Immunofluorescence experiments
confirmed PGRMC1's nucleolar localization in cultured bovine granulosa cells
(bGC) and oocytes. Additional experiments conducted on bGC revealed that PGRMC1
co-localizes with nucleolin (NCL), a major nucleolar protein. Furthermore, small
interfering RNA (RNAi)-mediated gene silencing experiments showed that when
PGRMC1 expression was depleted, NCL translocated from the nucleolus to the
nucleoplasm. Similarly, oxidative stress induced by hydrogen peroxide (H2O2)
treatment, reduced PGRMC1 immunofluorescent signal in the nucleolus and increased
NCL nucleoplasmic signal, when compared to non-treated cells. Although PGRMC1
influenced NCL localization, a direct interaction between these two proteins was
not detected using in situ proximity ligation assay. This suggests the
involvement of additional molecules in mediating the co-localization of PGRMC1
and nucleolin. Since nucleolin translocates into the nucleoplasm in response to
various cellular stressors, PGRMC1's ability to regulate its localization within
the nucleolus is likely an important component of mechanism by which cells
response to stress. This concept is consistent with PGRMC1's well-described
ability to promote ovarian cell survival and provides a rationale for future
studies on PGRMC1, NCL and the molecular mechanism by which these two proteins
protect against the adverse effect of cellular stressors, including oxidative
stress.
PMID- 29339454
TI - Chromatin remodeling in mammalian embryos.
AB - The mammalian embryo undergoes a dramatic amount of epigenetic remodeling during
the first week of development. In this review, we discuss several epigenetic
changes that happen over the course of cleavage development, focusing on covalent
marks (e.g., histone methylation and acetylation) and non-covalent remodeling
(chromatin remodeling via remodeling complexes; e.g., SWI/SNF-mediated chromatin
remodeling). Comparisons are also drawn between remodeling events that occur in
embryos from a variety of mammalian species.
PMID- 29339455
TI - High N-Acetyltransferase 1 Expression Is Associated with Estrogen Receptor
Expression in Breast Tumors, but Is not Under Direct Regulation by Estradiol,
5alpha-androstane-3beta,17beta-Diol, or Dihydrotestosterone in Breast Cancer
Cells.
AB - N-acetyltransferase 1 (NAT1) is an enzyme that metabolizes carcinogens, which
suggests a potential role in breast carcinogenesis. High NAT1 expression in
breast tumors is associated with estrogen receptor alpha (ERalpha+) and the
luminal subtype. We report that NAT1 mRNA transcript, protein, and enzyme
activity were higher in human breast tumors with high expression of ERalpha/ESR1
compared with normal breast tissue. There was a strong correlation between NATb
promoter and NAT1 protein expression/enzyme activity. High NAT1 expression in
tumors was not the result of adipocytes, as evidenced by low perilipin (PLIN)
expression. ESR1, NAT1, and XBP1 expression were associated in tumor biopsies.
Direct regulation of NAT1 transcription by estradiol (E2) was investigated in
ERalpha (+) MCF-7 and T47D breast cancer cells. E2 did not increase NAT1
transcript expression but increased progesterone receptor expression in a dose
dependent manner. Likewise, NAT1 transcript levels were not increased by
dihydrotestosterone (DHT) or 5alpha-androstane-3beta, (3beta-adiol) 17beta-diol.
Dithiothreitol increased levels of the activated, spliced XBP1 in ERalpha (+) MCF
7 and T47D breast cancer cells but did not affect NAT1 or ESR1 expression. We
conclude that NAT1 expression is not directly regulated by E2, DHT, 3beta-adiol,
or dithiothreitol despite high NAT1 and ESR1 expression in luminal A breast
cancer cells, suggesting that ESR1, XBP1, and NAT1 expression may share a common
transcriptional network arising from the luminal epithelium associated with
better survival in breast cancer. Clusters of high-expression genes, including
NAT1, in breast tumors might serve as potential targets for novel therapeutic
drug development.
PMID- 29339456
TI - PARP Inhibition Prevents Ethanol-Induced Neuroinflammatory Signaling and
Neurodegeneration in Rat Adult-Age Brain Slice Cultures.
AB - Using rat adult-age hippocampal-entorhinal cortical (HEC) slice cultures, we
examined the role of poly [ADP-ribose] polymerase (PARP) in binge ethanol's brain
inflammatory and neurodegenerative mechanisms. Activated by DNA strand breaks,
PARP (principally PARP1 in the brain) promotes DNA repair via poly [ADP-ribose]
(PAR) products, but PARP overactivation triggers regulated neuronal necrosis
(e.g., parthanatos). Previously, we found that brain PARP1 levels were
upregulated by neurotoxic ethanol binges in adult rats and HEC slices, and PARP
inhibitor PJ34 abrogated slice neurodegeneration. Binged HEC slices also
exhibited increased Ca+2-dependent phospholipase A2 (PLA2) isoenzymes (cPLA2 IVA
and sPLA2 IIA) that mobilize proinflammatory omega6 arachidonic acid (ARA). We
now find in 4-day-binged HEC slice cultures (100 mM ethanol) that PARP1
elevations after two overnight binges precede PAR, cPLA2, and sPLA2 enhancements
by 1 day and high-mobility group box-1 (HMGB1), an ethanol-responsive alarmin
that augments proinflammatory cytokines via toll-like receptor-4 (TLR4), by 2
days. After verifying that PJ34 effectively blocks PARP activity (?PAR), we
demonstrated that, like PJ34, three other PARP inhibitors-olaparib, veliparib,
and 4-aminobenzamide-provided neuroprotection from ethanol. Importantly, PJ34 and
olaparib also prevented ethanol's amplification of the PLA2 isoenzymes, and two
PLA2 inhibitors were neuroprotective-thus coupling PARP to PLA2, with PLA2
activity promoting neurodegeneration. Also, PJ34 and olaparib blocked ethanol
induced HMGB1 elevations, linking brain PARP induction to TLR4 activation. The
results provide evidence in adult brains that induction of PARP1 may mediate dual
neuroinflammatory pathways (PLA2->phospholipid->ARA and HMGB1->TLR4
>proinflammatory cytokines) that are complicit in binge ethanol-induced
neurodegeneration.
PMID- 29339457
TI - Curcumin Acts as a Positive Allosteric Modulator of alpha7-Nicotinic
Acetylcholine Receptors and Reverses Nociception in Mouse Models of Inflammatory
Pain.
AB - Effects of curcumin, a major ingredient of turmeric, were tested on the function
of the alpha7-subunit of the human nicotinic acetylcholine (alpha7-nACh) receptor
expressed in Xenopus oocytes and on nociception in mouse models of tonic and
visceral pain. Curcumin caused a significant potentiation of currents induced by
acetylcholine (ACh; 100 MUM) with an EC50 value of 0.2 uM. The effect of curcumin
was not dependent on the activation of G-proteins and protein kinases and did not
involve Ca2+-dependent Cl- channels expressed endogenously in oocytes.
Importantly, the extent of curcumin potentiation was enhanced significantly by
decreasing ACh concentrations. Curcumin did not alter specific binding of
[125I]alpha-bungarotoxin. In addition, curcumin attenuated nociceptive behavior
in both tonic and visceral pain models without affecting motor and locomotor
activity and without producing tolerance. Pharmacological and genetic approaches
revealed that the antinociceptive effect of curcumin was mediated by alpha7-nACh
receptors. Curcumin potentiated the antinociceptive effects of the alpha7-nACh
receptor agonist N-(3R)-1-azabicyclo[2.2.2]oct-3-yl-4-chlorobenzamide
(PNU282987). Collectively, our results indicate that curcumin is a positive
allosteric modulator of alpha7-nACh receptor and reverses nociception in mouse
models of tonic and visceral pain.
PMID- 29339458
TI - Coassociation between Group B Streptococcus and Candida albicans Promotes
Interactions with Vaginal Epithelium.
AB - Group B Streptococcus (GBS) is a leading cause of neonatal sepsis, pneumonia, and
meningitis worldwide. In the majority of cases, GBS is transmitted vertically
from mother to neonate, making maternal vaginal colonization a key risk factor
for neonatal disease. The fungus Candida albicans is an opportunistic pathogen of
the female genitourinary tract and the causative agent of vaginal thrush.
Carriage of C. albicans has been shown to be an independent risk factor for
vaginal colonization by GBS. However, the nature of interactions between these
two microbes is poorly understood. This study provides evidence of a reciprocal,
synergistic interplay between GBS and C. albicans that may serve to promote their
cocolonization of the vaginal mucosa. GBS strains NEM316 (serotype III) and 515
(serotype Ia) are shown to physically interact with C. albicans, with the
bacteria exhibiting tropism for candidal hyphal filaments. This interaction
enhances association levels of both microbes with the vaginal epithelial cell
line VK2/E6E7. The ability of GBS to coassociate with C. albicans is dependent
upon expression of the hypha-specific adhesin Als3. In turn, expression of GBS
antigen I/II family adhesins (Bsp polypeptides) facilitates this coassociation
and confers upon surrogate Lactococcus lactis the capacity to exhibit enhanced
interactions with C. albicans on vaginal epithelium. As genitourinary tract
colonization is an essential first step in the pathogenesis of GBS and C.
albicans, the coassociation mechanism reported here may have important
implications for the risk of disease involving both of these pathogens.
PMID- 29339459
TI - Novel Two-Component System of Streptococcus sanguinis Affecting Functions
Associated with Viability in Saliva and Biofilm Formation.
AB - Streptococcus sanguinis is a pioneer species of teeth and a common opportunistic
pathogen of infective endocarditis. In this study, we identified a two-component
system, S. sanguinis SptRS (SptRS Ss ), affecting S. sanguinis survival in saliva
and biofilm formation. Isogenic mutants of sptRSs (SKsptR) and sptSSs (SKsptS)
showed reduced cell counts in ex vivo assays of viability in saliva compared to
those of parent strain SK36 and complemented mutants. Reduced counts of the
mutants in saliva were associated with reduced growth rates in nutrient-poor
medium (RPMI) and increased susceptibility to the deposition of C3b and the
membrane attach complex (MAC) of the complement system, a defense component of
saliva and serum. Conversely, sptRSs and sptSSs mutants showed increased biofilm
formation associated with higher levels of production of H2O2 and extracellular
DNA. Reverse transcription-quantitative PCR (RT-qPCR) comparisons of strains
indicated a global role of SptRS Ss in repressing genes for H2O2 production (2.5-
to 15-fold upregulation of spxB, spxR, vicR, tpk, and ackA in sptRSs and sptSSs
mutants), biofilm formation, and/or evasion of host immunity (2.1- to 11.4-fold
upregulation of srtA, pcsB, cwdP, iga, and nt5e). Compatible with the homology of
SptR Ss with AraC-type regulators, duplicate to multiple conserved repeats were
identified in 1,000-bp regulatory regions of downstream genes, suggesting that
SptR Ss regulates transcription by DNA looping. Significant transcriptional
changes in the regulatory genes vicR, spxR, comE, comX, and mecA in the sptRSs
and sptSSs mutants further indicated that SptRS Ss is part of a regulatory
network that coordinates cell wall homeostasis, H2O2 production, and competence.
This study reveals that SptRS Ss is involved in the regulation of crucial
functions for S. sanguinis persistence in the oral cavity.
PMID- 29339460
TI - Dot/Icm-Translocated Proteins Important for Biogenesis of the Coxiella burnetii
Containing Vacuole Identified by Screening of an Effector Mutant Sublibrary.
AB - Coxiella burnetii is an intracellular pathogen that replicates in a lysosome
derived vacuole. A determinant necessary for C. burnetii virulence is the Dot/Icm
type IVB secretion system (T4SS). The Dot/Icm system delivers more than 100
proteins, called type IV effectors (T4Es), across the vacuolar membrane into the
host cell cytosol. Several T4Es have been shown to be important for vacuolar
biogenesis. Here, transposon (Tn) insertion sequencing technology (INSeq) was
used to identify C. burnetii Nine Mile phase II mutants in an arrayed library,
which facilitated the identification and clonal isolation of mutants deficient in
70 different T4E proteins. These effector mutants were screened in HeLa cells for
deficiencies in Coxiella-containing vacuole (CCV) biogenesis. This screen
identified and validated seven new T4Es that were important for vacuole
biogenesis. Loss-of-function mutations in cbu0414 (coxH1), cbu0513, cbu0978
(cem3), cbu1387 (cem6), cbu1524 (caeA), cbu1752, or cbu2028 resulted in a small
vacuole phenotype. These seven mutant strains produced small CCVs in all cells
tested, which included macrophage-like cells. The cbu2028::Tn mutant, though
unable to develop large CCVs, had intracellular replication rates similar to the
rate of the parental strain of C. burnetii, whereas the other six effector
mutants defective in CCV biogenesis displayed significant reductions in
intracellular replication. Vacuoles created by the cbu0513::Tn mutant did not
accumulate lipidated microtubule-associated protein 1A/1B light chain 3 (LC3-II),
suggesting a failure in fusion of the CCV with autophagosomes. These seven T4E
proteins add to the growing repertoire of C. burnetii factors that contribute to
CCV biogenesis.
PMID- 29339461
TI - Cooperative Immune Suppression by Escherichia coli and Shigella Effector
Proteins.
AB - The enteric attaching and effacing (A/E) pathogens enterohemorrhagic Escherichia
coli (EHEC) and enteropathogenic E. coli (EPEC) and the invasive pathogens
enteroinvasive E. coli (EIEC) and Shigella encode type III secretion systems
(T3SS) used to inject effector proteins into human host cells during infection.
Among these are a group of effectors required for NF-kappaB-mediated host immune
evasion. Recent studies have identified several effector proteins from A/E
pathogens and EIEC/Shigella that are involved in suppression of NF-kappaB and
have uncovered their cellular and molecular functions. A novel mechanism among
these effectors from both groups of pathogens is to coordinate effector function
during infection. This cooperativity among effector proteins explains how
bacterial pathogens are able to effectively suppress innate immune defense
mechanisms in response to diverse classes of immune receptor signaling complexes
(RSCs) stimulated during infection.
PMID- 29339462
TI - Direct Manipulation of T Lymphocytes by Proteins of Gastrointestinal Bacterial
Pathogens.
AB - Gastrointestinal bacterial infection represents a significant threat to human
health, as well as a burden on food animal production and welfare. Although there
is advanced knowledge about the molecular mechanisms underlying pathogenesis,
including the development of immune responses to these pathogens, gaps in
knowledge persist. It is well established that gastrointestinal bacterial
pathogens produce a myriad of proteins that affect the development and
effectiveness of innate immune responses. However, relatively few proteins that
directly affect lymphocytes responsible for humoral or cell-mediated immunity and
memory have been identified. Here, we review factors produced by gastrointestinal
bacterial pathogens that have direct T cell interactions and what is known about
their functions and mechanisms of action. T cell-interacting bacterial proteins
that have been identified to date mainly target three major T cell responses:
activation and expansion, chemotaxis, or apoptosis. Further, the requirement for
more focused studies to identify and understand additional mechanisms used by
bacteria to directly affect the T cell immune response and how these may
contribute to pathogenesis is highlighted. Increased knowledge in this area will
help to drive development of better interventions in prevention and treatment of
gastrointestinal bacterial infection.
PMID- 29339463
TI - Cell Cycle Arrest and Apoptosis Induced by Porphyromonas gingivalis Require Jun N
Terminal Protein Kinase- and p53-Mediated p38 Activation in Human Trophoblasts.
AB - Porphyromonas gingivalis, a periodontal pathogen, has been implicated as a
causative agent of preterm delivery of low-birth-weight infants. We previously
reported that P. gingivalis activated cellular DNA damage signaling pathways and
ERK1/2 that lead to G1 arrest and apoptosis in extravillous trophoblast cells
(HTR-8 cells) derived from the human placenta. In the present study, we further
examined alternative signaling pathways mediating cellular damage caused by P.
gingivalis. P. gingivalis infection of HTR-8 cells induced phosphorylation of p38
and Jun N-terminal protein kinase (JNK), while their inhibitors diminished both
G1 arrest and apoptosis. In addition, heat shock protein 27 (HSP27) was
phosphorylated through both p38 and JNK, and knockdown of HSP27 with small
interfering RNA (siRNA) prevented both G1 arrest and apoptosis. Furthermore,
regulation of G1 arrest and apoptosis was associated with p21 expression. HTR-8
cells infected with P. gingivalis exhibited upregulation of p21, which was
regulated by p53 and HSP27. These results suggest that P. gingivalis induces G1
arrest and apoptosis via novel molecular pathways that involve p38 and JNK with
its downstream effectors in human trophoblasts.
PMID- 29339467
TI - Profile of Scott W. Lowe.
PMID- 29339464
TI - Propionate enters GABAergic neurons, inhibits GABA transaminase, causes GABA
accumulation and lethargy in a model of propionic acidemia.
AB - Propionic acidemia is the accumulation of propionate in blood due to dysfunction
of propionyl-CoA carboxylase. The condition causes lethargy and striatal
degeneration with motor impairment in humans. How propionate exerts its toxic
effect is unclear. Here, we show that intravenous administration of propionate
causes dose-dependent propionate accumulation in the brain and transient lethargy
in mice. Propionate, an inhibitor of histone deacetylase, entered GABAergic
neurons, as could be seen from increased neuronal histone H4 acetylation in the
striatum and neocortex. Propionate caused an increase in GABA (gamma-amino
butyric acid) levels in the brain, suggesting inhibition of GABA breakdown. In
vitro propionate inhibited GABA transaminase with a Ki of ~1 mmol/l. In isolated
nerve endings, propionate caused increased release of GABA to the extracellular
fluid. In vivo, propionate reduced cerebral glucose metabolism in both striatum
and neocortex. We conclude that propionate-induced inhibition of GABA
transaminase causes accumulation of GABA in the brain, leading to increased
extracellular GABA concentration, which inhibits neuronal activity and causes
lethargy. Propionate-mediated inhibition of neuronal GABA transaminase, an enzyme
of the inner mitochondrial membrane, indicates entry of propionate into neuronal
mitochondria. However, previous work has shown that neurons are unable to
metabolize propionate oxidatively, leading us to conclude that propionyl-CoA
synthetase is probably absent from neuronal mitochondria. Propionate-induced
inhibition of energy metabolism in GABAergic neurons may render the striatum, in
which >90% of the neurons are GABAergic, particularly vulnerable to degeneration
in propionic acidemia.
PMID- 29339468
TI - Molecular epidemiology reveals the role of war in the spread of HIV in Ukraine.
AB - Ukraine has one of the largest HIV epidemics in Europe, historically driven by
people who inject drugs (PWID). The epidemic showed signs of stabilization in
2012, but the recent war in eastern Ukraine may be reigniting virus spread. We
investigated the movement of HIV-infected people within Ukraine before and during
the conflict. We analyzed HIV-1 subtype-A pol nucleotide sequences sampled during
2012-2015 from 427 patients of 24 regional AIDS centers and used phylogeographic
analysis to reconstruct virus movement among different locations in Ukraine. We
then tested for correlations between reported PWID behaviors and reconstructed
patterns of virus spread. Our analyses suggest that Donetsk and Lugansk, two
cities not controlled by the Ukrainian government in eastern Ukraine, were
significant exporters of the virus to the rest of the country. Additional
analyses showed that viral dissemination within the country changed after 2013.
Spearman correlation analysis showed that incoming virus flow was correlated with
the number of HIV-infected internally displaced people. Additionally, there was a
correlation between more intensive virus movement and locations with a higher
proportion of PWID practicing risky sexual behaviors. Our findings suggest that
effective prevention responses should involve internally displaced people and
people who frequently travel to war-affected regions. Scale-up of harm reduction
services for PWID will be an important factor in preventing new local HIV
outbreaks in Ukraine.
PMID- 29339470
TI - A randomized controlled design reveals barriers to citizenship for low-income
immigrants.
AB - Citizenship endows legal protections and is associated with economic and social
gains for immigrants and their communities. In the United States, however,
naturalization rates are relatively low. Yet we lack reliable knowledge as to
what constrains immigrants from applying. Drawing on data from a public/private
naturalization program in New York, this research provides a randomized
controlled study of policy interventions that address these constraints. The
study tested two programmatic interventions among low-income immigrants who are
eligible for citizenship. The first randomly assigned a voucher that covers the
naturalization application fee among immigrants who otherwise would have to pay
the full cost of the fee. The second randomly assigned a set of behavioral
nudges, similar to outreach efforts used by service providers, among immigrants
whose incomes were low enough to qualify them for a federal waiver that
eliminates the application fee. Offering the fee voucher increased naturalization
application rates by about 41%, suggesting that application fees act as a barrier
for low-income immigrants who want to become US citizens. The nudges to encourage
the very poor to apply had no discernible effect, indicating the presence of
nonfinancial barriers to naturalization.
PMID- 29339469
TI - The Bardet-Biedl syndrome protein complex is an adapter expanding the cargo range
of intraflagellar transport trains for ciliary export.
AB - Bardet-Biedl syndrome (BBS) is a ciliopathy resulting from defects in the BBSome,
a conserved protein complex. BBSome mutations affect ciliary membrane
composition, impairing cilia-based signaling. The mechanism by which the BBSome
regulates ciliary membrane content remains unknown. Chlamydomonas bbs mutants
lack phototaxis and accumulate phospholipase D (PLD) in the ciliary membrane.
Single particle imaging revealed that PLD comigrates with BBS4 by intraflagellar
transport (IFT) while IFT of PLD is abolished in bbs mutants. BBSome deficiency
did not alter the rate of PLD entry into cilia. Membrane association and the N
terminal 58 residues of PLD are sufficient and necessary for BBSome-dependent
transport and ciliary export. The replacement of PLD's ciliary export sequence
(CES) caused PLD to accumulate in cilia of cells with intact BBSomes and IFT. The
buildup of PLD inside cilia impaired phototaxis, revealing that PLD is a negative
regulator of phototactic behavior. We conclude that the BBSome is a cargo adapter
ensuring ciliary export of PLD on IFT trains to regulate phototaxis.
PMID- 29339471
TI - Laminar recordings in frontal cortex suggest distinct layers for maintenance and
control of working memory.
AB - All of the cerebral cortex has some degree of laminar organization. These
different layers are composed of neurons with distinct connectivity patterns,
embryonic origins, and molecular profiles. There are little data on the laminar
specificity of cognitive functions in the frontal cortex, however. We recorded
neuronal spiking/local field potentials (LFPs) using laminar probes in the
frontal cortex (PMd, 8A, 8B, SMA/ACC, DLPFC, and VLPFC) of monkeys performing
working memory (WM) tasks. LFP power in the gamma band (50-250 Hz) was strongest
in superficial layers, and LFP power in the alpha/beta band (4-22 Hz) was
strongest in deep layers. Memory delay activity, including spiking and stimulus
specific gamma bursting, was predominately in superficial layers. LFPs from
superficial and deep layers were synchronized in the alpha/beta bands. This was
primarily unidirectional, with alpha/beta bands in deep layers driving
superficial layer activity. The phase of deep layer alpha/beta modulated
superficial gamma bursting associated with WM encoding. Thus, alpha/beta rhythms
in deep layers may regulate the superficial layer gamma bands and hence
maintenance of the contents of WM.
PMID- 29339472
TI - miRNA-mediated targeting of human cytomegalovirus reveals biological host and
viral targets of IE2.
AB - Human cytomegalovirus (HCMV) impacts more than one-half of the human population
owing to its capacity to manipulate the cell and create latent reservoirs in the
host. Despite an extensive understanding of HCMV biology during acute infection
in fibroblasts, the molecular basis for latency in myeloid cells remains
incomplete. This knowledge gap is due largely to the fact that the existing
genetic systems require virus rescue in fibroblasts, precluding the study of
genes that are essential during acute infection, yet likely play unique roles in
myeloid cells or the establishment of latency. Here we present a solution to
address this restriction. Through the exploitation of a hematopoietic-specific
microRNA, we demonstrate a one-step recombineering approach that enables gene
silencing only in cells associated with latency. As a proof of concept, here we
describe a TB40/E variant that undergoes hematopoietic targeting of the Immediate
Early-2 (IE2) gene to explore its function during infection of myeloid cells.
While virus replication of the hematopoietic-targeted IE2 variant was unimpaired
in fibroblasts, we observed a >100-fold increase in virus titers in myeloid
cells. Virus replication in myeloid cells demonstrated that IE2 has a significant
transcriptional footprint on both viral and host genes. These data implicate IE2
as an essential mediator of virus biology in myeloid cells and illustrate the
utility of cell-specific microRNA-based targeting.
PMID- 29339473
TI - Identification of thioredoxin-interacting protein (TXNIP) as a downstream target
for IGF1 action.
AB - Laron syndrome (LS), or primary growth hormone (GH) insensitivity, is the best
characterized entity among the congenital insulin-like growth factor 1 (IGF1)
deficiencies. Life-long exposure to minute endogenous IGF1 levels is linked to
low stature as well as a number of endocrine and metabolic abnormalities. While
elevated IGF1 is correlated with increased cancer incidence, epidemiological
studies revealed that patients with LS do not develop tumors. The mechanisms
associated with cancer protection in LS are yet to be discovered. Recent genomic
analyses identified a series of metabolic genes that are overrepresented in
patients with LS. Given the augmented expression of these genes in a low IGF1
milieu, we hypothesized that they may constitute targets for IGF1 action.
Thioredoxin-interacting protein (TXNIP) plays a critical role in cellular redox
control by thioredoxin. TXNIP serves as a glucose and oxidative stress sensor,
being commonly silenced by genetic or epigenetic events in cancer cells.
Consistent with its enhanced expression in LS, we provide evidence that TXNIP
gene expression is negatively regulated by IGF1. These results were corroborated
in animal studies. In addition, we show that oxidative and glucose stresses led
to marked increases in TXNIP expression. Supplementation of IGF1 attenuated TXNIP
levels, suggesting that IGF1 exerts its antiapoptotic effect via inhibition of
TXNIP Augmented TXNIP expression in LS may account for cancer protection in this
condition. Finally, TXNIP levels could be potentially useful in the clinic as a
predictive or diagnostic biomarker for IGF1R-targeted therapies.
PMID- 29339474
TI - Robust prediction of individual creative ability from brain functional
connectivity.
AB - People's ability to think creatively is a primary means of technological and
cultural progress, yet the neural architecture of the highly creative brain
remains largely undefined. Here, we employed a recently developed method in
functional brain imaging analysis-connectome-based predictive modeling-to
identify a brain network associated with high-creative ability, using functional
magnetic resonance imaging (fMRI) data acquired from 163 participants engaged in
a classic divergent thinking task. At the behavioral level, we found a strong
correlation between creative thinking ability and self-reported creative behavior
and accomplishment in the arts and sciences (r = 0.54). At the neural level, we
found a pattern of functional brain connectivity related to high-creative
thinking ability consisting of frontal and parietal regions within default,
salience, and executive brain systems. In a leave-one-out cross-validation
analysis, we show that this neural model can reliably predict the creative
quality of ideas generated by novel participants within the sample. Furthermore,
in a series of external validation analyses using data from two independent task
fMRI samples and a large task-free resting-state fMRI sample, we demonstrate
robust prediction of individual creative thinking ability from the same pattern
of brain connectivity. The findings thus reveal a whole-brain network associated
with high-creative ability comprised of cortical hubs within default, salience,
and executive systems-intrinsic functional networks that tend to work in
opposition-suggesting that highly creative people are characterized by the
ability to simultaneously engage these large-scale brain networks.
PMID- 29339475
TI - Electron mean-free-path filtering in Dirac material for improved thermoelectric
performance.
AB - Recent advancements in thermoelectric materials have largely benefited from
various approaches, including band engineering and defect optimization, among
which the nanostructuring technique presents a promising way to improve the
thermoelectric figure of merit (zT) by means of reducing the characteristic
length of the nanostructure, which relies on the belief that phonons' mean free
paths (MFPs) are typically much longer than electrons'. Pushing the nanostructure
sizes down to the length scale dictated by electron MFPs, however, has hitherto
been overlooked as it inevitably sacrifices electrical conduction. Here we report
through ab initio simulations that Dirac material can overcome this limitation.
The monotonically decreasing trend of the electron MFP allows filtering of long
MFP electrons that are detrimental to the Seebeck coefficient, leading to a
dramatically enhanced power factor. Using SnTe as a material platform, we uncover
this MFP filtering effect as arising from its unique nonparabolic Dirac band
dispersion. Room-temperature zT can be enhanced by nearly a factor of 3 if one
designs nanostructures with grain sizes of ~10 nm. Our work broadens the scope of
the nanostructuring approach for improving the thermoelectric performance,
especially for materials with topologically nontrivial electronic dynamics.
PMID- 29339476
TI - Coding of episodic memory in the human hippocampus.
AB - Neurocomputational models have long posited that episodic memories in the human
hippocampus are represented by sparse, stimulus-specific neural codes. A
concomitant proposal is that when sparse-distributed neural assemblies become
active, they suppress the activity of competing neurons (neural sharpening). We
investigated episodic memory coding in the hippocampus and amygdala by measuring
single-neuron responses from 20 epilepsy patients (12 female) undergoing
intracranial monitoring while they completed a continuous recognition memory
task. In the left hippocampus, the distribution of single-neuron activity
indicated that only a small fraction of neurons exhibited strong responding to a
given repeated word and that each repeated word elicited strong responding in a
different small fraction of neurons. This finding reflects sparse distributed
coding. The remaining large fraction of neurons exhibited a concurrent reduction
in firing rates relative to novel words. The observed pattern accords with
longstanding predictions that have previously received scant support from single
cell recordings from human hippocampus.
PMID- 29339477
TI - Ebola virus proteins NP, VP35, and VP24 are essential and sufficient to mediate
nucleocapsid transport.
AB - The intracytoplasmic movement of nucleocapsids is a crucial step in the life
cycle of enveloped viruses. Determination of the viral components necessary for
viral nucleocapsid transport competency is complicated by the dynamic and complex
nature of nucleocapsid assembly and the lack of appropriate model systems. Here,
we established a live-cell imaging system based on the ectopic expression of
fluorescent Ebola virus (EBOV) fusion proteins, allowing the visualization and
analysis of the movement of EBOV nucleocapsid-like structures with different
protein compositions. Only three of the five EBOV nucleocapsid proteins
nucleoprotein, VP35, and VP24-were necessary and sufficient to form transport
competent nucleocapsid-like structures. The transport of these structures was
found to be dependent on actin polymerization and to have dynamics that were
undistinguishable from those of nucleocapsids in EBOV-infected cells. The
intracytoplasmic movement of nucleocapsid-like structures was completely
independent of the viral matrix protein VP40 and the viral surface glycoprotein
GP. However, VP40 greatly enhanced the efficiency of nucleocapsid recruitment
into filopodia, the sites of EBOV budding.
PMID- 29339478
TI - Cooperation, clustering, and assortative mixing in dynamic networks.
AB - Humans' propensity to cooperate is driven by our embeddedness in social networks.
A key mechanism through which networks promote cooperation is clustering. Within
clusters, conditional cooperators are insulated from exploitation by
noncooperators, allowing them to reap the benefits of cooperation. Dynamic
networks, where ties can be shed and new ties formed, allow for the endogenous
emergence of clusters of cooperators. Although past work suggests that either
reputation processes or network dynamics can increase clustering and cooperation,
existing work on network dynamics conflates reputations and dynamics. Here we
report results from a large-scale experiment (total n = 2,675) that embedded
participants in clustered or random networks that were static or dynamic, with
varying levels of reputational information. Results show that initial network
clustering predicts cooperation in static networks, but not in dynamic ones.
Further, our experiment shows that while reputations are important for partner
choice, cooperation levels are driven purely by dynamics. Supplemental conditions
confirmed this lack of a reputation effect. Importantly, we find that when
participants make individual choices to cooperate or defect with each partner, as
opposed to a single decision that applies to all partners (as is standard in the
literature on cooperation in networks), cooperation rates in static networks are
as high as cooperation rates in dynamic networks. This finding highlights the
importance of structured relations for sustained cooperation, and shows how
giving experimental participants more realistic choices has important
consequences for whether dynamic networks promote higher levels of cooperation
than static networks.
PMID- 29339480
TI - Local policy proposals can bridge Latino and (most) white Americans' response to
immigration.
AB - In the past 15 years, the adoption of subnational immigration policies in the
United States, such as those established by individual states, has gone from
nearly zero to over 300 per year. These include welcoming policies aimed at
attracting and incorporating immigrants, as well as unwelcoming policies directed
at denying immigrants access to public resources and services. Using data from a
2016 random digit-dialing telephone survey with an embedded experiment, we
examine whether institutional support for policies that are either welcoming or
hostile toward immigrants differentially shape Latinos' and whites' feelings of
belonging in their state (Arizona/New Mexico, adjacent states with contrasting
immigration policies). We randomly assigned individuals from the representative
sample (n = 1,903) of Latinos (US and foreign born) and whites (all US born) to
consider policies that were either welcoming of or hostile toward immigrants.
Across both states of residence, Latinos, especially those foreign born,
regardless of citizenship, expressed more positive affect and greater belonging
when primed with a welcoming (vs. hostile) policy. Demonstrating the importance
of local norms, these patterns held among US-born whites, except among self
identified politically conservative whites, who showed more negative affect and
lower levels of belonging in response to welcoming policies. Thus, welcoming
immigration policies, supported by institutional authorities, can create a sense
of belonging not only among newcomers that is vital to successful integration but
also among a large segment of the population that is not a direct beneficiary of
such policies-US-born whites.
PMID- 29339479
TI - HIF signaling in osteoblast-lineage cells promotes systemic breast cancer growth
and metastasis in mice.
AB - Bone metastasis involves dynamic interplay between tumor cells and the local
stromal environment. In bones, local hypoxia and activation of the hypoxia
inducible factor (HIF)-1alpha in osteoblasts are essential to maintain skeletal
homeostasis. However, the role of osteoblast-specific HIF signaling in cancer
metastasis is unknown. Here, we show that osteoprogenitor cells (OPCs) are
located in hypoxic niches in the bone marrow and that activation of HIF signaling
in these cells increases bone mass and favors breast cancer metastasis to bone
locally. Remarkably, HIF signaling in osteoblast-lineage cells also promotes
breast cancer growth and dissemination remotely, in the lungs and in other
tissues distant from bones. Mechanistically, we found that activation of HIF
signaling in OPCs increases blood levels of the chemokine C-X-C motif ligand 12
(CXCL12), which leads to a systemic increase of breast cancer cell proliferation
and dissemination through direct activation of the CXCR4 receptor. Hence, our
data reveal a previously unrecognized role of the hypoxic osteogenic niche in
promoting tumorigenesis beyond the local bone microenvironment. They also support
the concept that the skeleton is an important regulator of the systemic tumor
environment.
PMID- 29339481
TI - Repetitive aggressive encounters generate a long-lasting internal state in
Drosophila melanogaster males.
AB - Multiple studies have investigated the mechanisms of aggressive behavior in
Drosophila; however, little is known about the effects of chronic fighting
experience. Here, we investigated if repeated fighting encounters would induce an
internal state that could affect the expression of subsequent behavior. We
trained wild-type males to become winners or losers by repeatedly pairing them
with hypoaggressive or hyperaggressive opponents, respectively. As described
previously, we observed that chronic losers tend to lose subsequent fights, while
chronic winners tend to win them. Olfactory conditioning experiments showed that
winning is perceived as rewarding, while losing is perceived as aversive.
Moreover, the effect of chronic fighting experience generalized to other
behaviors, such as gap-crossing and courtship. We propose that in response to
repeatedly winning or losing aggressive encounters, male flies form an internal
state that displays persistence and generalization; fight outcomes can also have
positive or negative valence. Furthermore, we show that the activities of the
PPL1-gamma1pedc dopaminergic neuron and the MBON-gamma1pedc>alpha/beta mushroom
body output neuron are required for aversion to an olfactory cue associated with
losing fights.
PMID- 29339482
TI - Global spectral clustering in dynamic networks.
AB - Community detection is challenging when the network structure is estimated with
uncertainty. Dynamic networks present additional challenges but also add
information across time periods. We propose a global community detection method,
persistent communities by eigenvector smoothing (PisCES), that combines
information across a series of networks, longitudinally, to strengthen the
inference for each period. Our method is derived from evolutionary spectral
clustering and degree correction methods. Data-driven solutions to the problem of
tuning parameter selection are provided. In simulations we find that PisCES
performs better than competing methods designed for a low signal-to-noise ratio.
Recently obtained gene expression data from rhesus monkey brains provide samples
from finely partitioned brain regions over a broad time span including pre- and
postnatal periods. Of interest is how gene communities develop over space and
time; however, once the data are divided into homogeneous spatial and temporal
periods, sample sizes are very small, making inference quite challenging.
Applying PisCES to medial prefrontal cortex in monkey rhesus brains from near
conception to adulthood reveals dense communities that persist, merge, and
diverge over time and others that are loosely organized and short lived,
illustrating how dynamic community detection can yield interesting insights into
processes such as brain development.
PMID- 29339484
TI - Probabilistic switching circuits in DNA.
AB - A natural feature of molecular systems is their inherent stochastic behavior. A
fundamental challenge related to the programming of molecular information
processing systems is to develop a circuit architecture that controls the
stochastic states of individual molecular events. Here we present a systematic
implementation of probabilistic switching circuits, using DNA strand displacement
reactions. Exploiting the intrinsic stochasticity of molecular interactions, we
developed a simple, unbiased DNA switch: An input signal strand binds to the
switch and releases an output signal strand with probability one-half. Using this
unbiased switch as a molecular building block, we designed DNA circuits that
convert an input signal to an output signal with any desired probability.
Further, this probability can be switched between 2 n different values by simply
varying the presence or absence of n distinct DNA molecules. We demonstrated
several DNA circuits that have multiple layers and feedback, including a circuit
that converts an input strand to an output strand with eight different
probabilities, controlled by the combination of three DNA molecules. These
circuits combine the advantages of digital and analog computation: They allow a
small number of distinct input molecules to control a diverse signal range of
output molecules, while keeping the inputs robust to noise and the outputs at
precise values. Moreover, arbitrarily complex circuit behaviors can be
implemented with just a single type of molecular building block.
PMID- 29339483
TI - HELLS and CDCA7 comprise a bipartite nucleosome remodeling complex defective in
ICF syndrome.
AB - Mutations in CDCA7, the SNF2 family protein HELLS (LSH), or the DNA
methyltransferase DNMT3b cause immunodeficiency-centromeric instability-facial
anomalies (ICF) syndrome. While it has been speculated that DNA methylation
defects cause this disease, little is known about the molecular function of CDCA7
and its functional relationship to HELLS and DNMT3b. Systematic analysis of how
the cell cycle, H3K9 methylation, and the mitotic kinase Aurora B affect
proteomic profiles of chromatin in Xenopus egg extracts revealed that HELLS and
CDCA7 form a stoichiometric complex on chromatin, in a manner sensitive to Aurora
B. Although HELLS alone fails to remodel nucleosomes, we demonstrate that the
HELLS-CDCA7 complex possesses nucleosome remodeling activity. Furthermore, CDCA7
is essential for loading HELLS onto chromatin, and CDCA7 harboring patient ICF
mutations fails to recruit the complex to chromatin. Together, our study
identifies a unique bipartite nucleosome remodeling complex where the functional
remodeling activity is split between two proteins and thus delineates the
defective pathway in ICF syndrome.
PMID- 29339485
TI - Elevated d-2-hydroxyglutarate during colitis drives progression to colorectal
cancer.
AB - d-2-hydroxyglutarate (D2HG) is produced in the tricarboxylic acid cycle and is
quickly converted to alpha-ketoglutarate by d-2-hydroxyglutarate dehydrogenase
(D2HGDH). In a mouse model of colitis-associated colon cancer (CAC), urine level
of D2HG during colitis correlates positively with subsequent polyp counts and
severity of dysplasia. The i.p. injection of D2HG results in delayed recovery
from colitis and severe tumorigenesis. The colonic expression of D2HGDH is
decreased in ulcerative colitis (UC) patients at baseline who progress to cancer.
Hypoxia-inducible factor (Hif)-1alpha is a key regulator of D2HGDH transcription.
Our study identifies urine D2HG and tissue D2HGDH expression as biomarkers to
identify patients at risk for progressing from colitis to cancer. The D2HG/D2HGDH
pathway provides potential therapeutic targets for the treatment of CAC.
PMID- 29339487
TI - Uncovering the role of the East Asian jet stream and heterogeneities in
atmospheric rivers affecting the western United States.
AB - Atmospheric rivers (ARs) exert major socioeconomic repercussions along the US
West Coast by inducing heavy rainfall, flooding, strong winds, and storm surge.
Despite the significant societal and economic repercussions of these storms, our
understanding of the physical drivers responsible for their interannual
variability is limited, with different climate modes identified as possible
mechanisms. Here we show that the Pacific-Japan (PJ) teleconnections/patterns and
the East Asian subtropical jet (EASJ) exhibit a strong linkage with the total
frequency of ARs making landfall over the western United States, much stronger
than the other potential climate modes previously considered. While our findings
indicate that the PJ pattern and EASJ are the most relevant climate modes driving
the overall AR activity, we also uncover heterogeneities in AR tracks.
Specifically, we show that not all ARs making landfall along the West Coast come
from a single population, but rather that it is possible to stratify these storms
into three clusters. While the PJ pattern and EASJ are major drivers of AR
activity for two clusters, the cluster that primarily affects the US Southwest is
largely driven by other climate modes [El Nino Southern Oscillation (ENSO), the
Atlantic meridional mode (AMM), the Pacific-North America (PNA) teleconnection
pattern, and the North Pacific Gyre Oscillation (NPGO)]. Therefore, important
regional differences exist and this information can substantially enhance our
ability to predict and prepare for these storms and their impacts.
PMID- 29339486
TI - Cell-type-specific role for nucleus accumbens neuroligin-2 in depression and
stress susceptibility.
AB - Behavioral coping strategies are critical for active resilience to stress and
depression; here we describe a role for neuroligin-2 (NLGN-2) in the nucleus
accumbens (NAc). Neuroligins (NLGN) are a family of neuronal postsynaptic cell
adhesion proteins that are constituents of the excitatory and inhibitory synapse.
Importantly, NLGN-3 and NLGN-4 mutations are strongly implicated as candidates
underlying the development of neuropsychiatric disorders with social disturbances
such as autism, but the role of NLGN-2 in neuropsychiatric disease states is
unclear. Here we show a reduction in NLGN-2 gene expression in the NAc of
patients with major depressive disorder. Chronic social defeat stress in mice
also decreases NLGN-2 selectively in dopamine D1-positive cells, but not dopamine
D2-positive cells, within the NAc of stress-susceptible mice. Functional NLGN-2
knockdown produces bidirectional, cell-type-specific effects: knockdown in
dopamine D1-positive cells promotes subordination and stress susceptibility,
whereas knockdown in dopamine D2-positive cells mediates active defensive
behavior. These findings establish a behavioral role for NAc NLGN-2 in stress and
depression; provide a basis for targeted, cell-type specific therapy; and
highlight the role of active behavioral coping mechanisms in stress
susceptibility.
PMID- 29339489
TI - Rogue waves and large deviations in deep sea.
AB - The appearance of rogue waves in deep sea is investigated by using the modified
nonlinear Schrodinger (MNLS) equation in one spatial dimension with random
initial conditions that are assumed to be normally distributed, with a spectrum
approximating realistic conditions of a unidirectional sea state. It is shown
that one can use the incomplete information contained in this spectrum as prior
and supplement this information with the MNLS dynamics to reliably estimate the
probability distribution of the sea surface elevation far in the tail at later
times. Our results indicate that rogue waves occur when the system hits unlikely
pockets of wave configurations that trigger large disturbances of the surface
height. The rogue wave precursors in these pockets are wave patterns of regular
height, but with a very specific shape that is identified explicitly, thereby
allowing for early detection. The method proposed here combines Monte Carlo
sampling with tools from large deviations theory that reduce the calculation of
the most likely rogue wave precursors to an optimization problem that can be
solved efficiently. This approach is transferable to other problems in which the
system's governing equations contain random initial conditions and/or parameters.
PMID- 29339488
TI - Ultrafast imaging of cell elasticity with optical microelastography.
AB - Elasticity is a fundamental cellular property that is related to the anatomy,
functionality, and pathological state of cells and tissues. However, current
techniques based on cell deformation, atomic force microscopy, or Brillouin
scattering are rather slow and do not always accurately represent cell
elasticity. Here, we have developed an alternative technique by applying shear
wave elastography to the micrometer scale. Elastic waves were mechanically
induced in live mammalian oocytes using a vibrating micropipette. These audible
frequency waves were observed optically at 200,000 frames per second and tracked
with an optical flow algorithm. Whole-cell elasticity was then mapped using an
elastography method inspired by the seismology field. Using this approach we show
that the elasticity of mouse oocytes is decreased when the oocyte cytoskeleton is
disrupted with cytochalasin B. The technique is fast (less than 1 ms for data
acquisition), precise (spatial resolution of a few micrometers), able to map
internal cell structures, and robust and thus represents a tractable option for
interrogating biomechanical properties of diverse cell types.
PMID- 29339490
TI - Structural basis of sterol recognition and nonvesicular transport by lipid
transfer proteins anchored at membrane contact sites.
AB - Membrane contact sites (MCSs) in eukaryotic cells are hotspots for lipid
exchange, which is essential for many biological functions, including regulation
of membrane properties and protein trafficking. Lipid transfer proteins anchored
at membrane contact sites (LAMs) contain sterol-specific lipid transfer domains
[StARkin domain (SD)] and multiple targeting modules to specific membrane
organelles. Elucidating the structural mechanisms of targeting and ligand
recognition by LAMs is important for understanding the interorganelle
communication and exchange at MCSs. Here, we determined the crystal structures of
the yeast Lam6 pleckstrin homology (PH)-like domain and the SDs of Lam2 and Lam4
in the apo form and in complex with ergosterol. The Lam6 PH-like domain displays
a unique PH domain fold with a conserved N-terminal alpha-helix. The Lam6 PH-like
domain lacks the basic surface for phosphoinositide binding, but contains
hydrophobic patches on its surface, which are critical for targeting to
endoplasmic reticulum (ER)-mitochondrial contacts. Structures of the LAM SDs
display a helix-grip fold with a hydrophobic cavity and a flexible Omega1-loop as
a lid. Ergosterol is bound to the pocket in a head-down orientation, with its
hydrophobic acyl group located in the tunnel entrance. The Omega1-loop in an open
conformation is essential for ergosterol binding by direct hydrophobic
interaction. Structural comparison suggested that the sterol binding mode of the
Lam2 SD2 is likely conserved among the sterol transfer proteins of the StARkin
superfamily. Structural models of full-length Lam2 correlated with the sterol
transport function at the membrane contact sites.
PMID- 29339491
TI - Kinase-independent function of E-type cyclins in liver cancer.
AB - E-type cyclins (cyclins E1 and E2) are components of the core cell cycle
machinery and are overexpressed in many human tumor types. E cyclins are thought
to drive tumor cell proliferation by activating the cyclin-dependent kinase 2
(CDK2). The cyclin E1 gene represents the site of recurrent integration of the
hepatitis B virus in the pathogenesis of hepatocellular carcinoma, and this event
is associated with strong up-regulation of cyclin E1 expression. Regardless of
the underlying mechanism of tumorigenesis, the majority of liver cancers
overexpress E-type cyclins. Here we used conditional cyclin E knockout mice and a
liver cancer model to test the requirement for the function of E cyclins in liver
tumorigenesis. We show that a ubiquitous, global shutdown of E cyclins did not
visibly affect postnatal development or physiology of adult mice. However, an
acute ablation of E cyclins halted liver cancer progression. We demonstrated that
also human liver cancer cells critically depend on E cyclins for proliferation.
In contrast, we found that the function of the cyclin E catalytic partner, CDK2,
is dispensable in liver cancer cells. We observed that E cyclins drive
proliferation of tumor cells in a CDK2- and kinase-independent mechanism. Our
study suggests that compounds which degrade or inhibit cyclin E might represent a
highly selective therapeutic strategy for patients with liver cancer, as these
compounds would selectively cripple proliferation of tumor cells, while sparing
normal tissues.
PMID- 29339492
TI - Cytocapsular tubes conduct cell translocation.
AB - Cell locomotion is essential for multicellular organism embryo development, organ
homeostasis, tissue regeneration, immune responses, and tumor metastasis. Here we
report that single mammalian cells can generate two extracellular membranous
compartments: cytocapsulae and cytocapsular tubes. Cells migrate in cytocapsulae
and engender cytocapsular tubes, which exhibit pleiotropic biological functions
and provide tubular routes for directed cell transportation. Ultrastructural
analysis by electron microscope revealed that nanoprotrusions surround and anchor
cytocapsular tubes in place. Multiple cytocapsular tubes interconnect and form
networks supporting directed cell transportation in diverse directions. Enhanced
translation initiation factor eIF4E up-regulates translation of transcripts
encoding proteins important for organelle development. Thus, this study proposes
a mechanism of directed cell translocation in cytocapsular tubes, which may
facilitate the management of diseases, including tumor metastasis.
PMID- 29339493
TI - Emergent chirality in the electric polarization texture of titanate
superlattices.
AB - Chirality is a geometrical property by which an object is not superimposable onto
its mirror image, thereby imparting a handedness. Chirality determines many
important properties in nature-from the strength of the weak interactions
according to the electroweak theory in particle physics to the binding of enzymes
with naturally occurring amino acids or sugars, reactions that are fundamental
for life. In condensed matter physics, the prediction of topologically protected
magnetic skyrmions and related spin textures in chiral magnets has stimulated
significant research. If the magnetic dipoles were replaced by their electrical
counterparts, then electrically controllable chiral devices could be designed.
Complex oxide BaTiO3/SrTiO3 nanocomposites and PbTiO3/SrTiO3 superlattices are
perfect candidates, since "polar vortices," in which a continuous rotation of
ferroelectric polarization spontaneously forms, have been recently discovered.
Using resonant soft X-ray diffraction, we report the observation of a strong
circular dichroism from the interaction between circularly polarized light and
the chiral electric polarization texture that emerges in PbTiO3/SrTiO3
superlattices. This hallmark of chirality is explained by a helical rotation of
electric polarization that second-principles simulations predict to reside within
complex 3D polarization textures comprising ordered topological line defects. The
handedness of the texture can be topologically characterized by the sign of the
helicity number of the chiral line defects. This coupling between the optical and
novel polar properties could be exploited to encode chiral signatures into photon
or electron beams for information processing.
PMID- 29339494
TI - Strongly enhanced bacterial bioluminescence with the ilux operon for single-cell
imaging.
AB - Bioluminescence imaging of single cells is often complicated by the requirement
of exogenous luciferins that can be poorly cell-permeable or produce high
background signal. Bacterial bioluminescence is unique in that it uses reduced
flavin mononucleotide as a luciferin, which is abundant in all cells, making this
system purely genetically encodable by the lux operon. Unfortunately, the use of
bacterial bioluminescence has been limited by its low brightness compared with
other luciferases. Here, we report the generation of an improved lux operon named
ilux with an approximately sevenfold increased brightness when expressed in
Escherichia coli; ilux can be used to image single E. coli cells with enhanced
spatiotemporal resolution over several days. In addition, since only
metabolically active cells produce bioluminescent signal, we show that ilux can
be used to observe the effect of different antibiotics on cell viability on the
single-cell level.
PMID- 29339495
TI - Streamlined circular proximity ligation assay provides high stringency and
compatibility with low-affinity antibodies.
AB - Proximity ligation assay (PLA) is a powerful tool for quantitative detection of
protein biomarkers in biological fluids and tissues. Here, we present the
circular proximity ligation assay (c-PLA), a highly specific protein detection
method that outperforms traditional PLA in stringency, ease of use, and
compatibility with low-affinity reagents. In c-PLA, two proximity probes bind to
an analyte, providing a scaffolding that positions two free oligonucleotides such
that they can be ligated into a circular DNA molecule. This assay format
stabilizes antigen proximity probe complexes and enhances stringency by reducing
the probability of random background ligation events. Circle formation also
increases selectivity, since the uncircularized DNA can be removed enzymatically.
We compare this method with traditional PLA on several biomarkers and show that
the higher stringency for c-PLA improves reproducibility and enhances sensitivity
in both buffer and human plasma. The limit of detection ranges from femtomolar to
nanomolar concentrations for both methods. Kinetic analyses using surface plasmon
resonance (SPR) and biolayer interferometry (BLI) reveal that the variation in
limit of detection is due to the variation in antibody affinity and that c-PLA
outperforms traditional PLA for low-affinity antibodies. The lower background
signal can be used to increase proximity probe concentration while maintaining a
high signal-to-noise ratio, thereby enabling the use of low-affinity reagents in
a homogeneous assay format. We anticipate that the advantages of c-PLA will be
useful in a variety of clinical protein detection applications where high
affinity reagents are lacking.
PMID- 29339496
TI - Thymic stromal lymphopoietin drives the development of IL-13+ Th2 cells.
AB - T helper 2 (Th2) cells are pivotal in the development of allergy. Allergen
exposure primes IL-4+ Th2 cells in lymph node, but production of effector
cytokines including IL-5 and IL-13 is thought to require additional signals from
antigen and the environment. Here we report that a substantial proportion of
naive CD4+ T cells in spleen and lymph node express receptors for the epithelium
derived inflammatory cytokine thymic stromal lymphopoietin (TSLP). Culture of
naive CD4+ T cells in anti-(a)CD3, aCD28, and TSLP-supplemented Th2 conditions
enabled the development of a unique population of IL-13-single positive (IL-13
SP) CD4+ T cells; TSLP and Th2 conditions were both required for their
development. Sorting experiments revealed that IL-13-SP Th2 cells originated from
IL-4-negative precursors and coexpressed transcripts for the Th2 cytokines IL-5
and IL-9. In vivo, high TSLP levels acted directly on CD4+ T cells to induce the
development of IL-13-SP and IL-4+IL-13+ double-positive populations in lymph
node. These cells were phenotypically similar to Th2 effector cells and were
CXCR5lowPD1low and expressed low levels of Bcl6 and Il21 transcripts and high
levels of Gata3, Il3, and Il5 Our findings suggest a role of TSLP in directly
promoting Th2 cell effector function and support the notion of TSLP as a key
driver of Th2 inflammation.
PMID- 29339497
TI - Ocean convergence and the dispersion of flotsam.
AB - Floating oil, plastics, and marine organisms are continually redistributed by
ocean surface currents. Prediction of their resulting distribution on the surface
is a fundamental, long-standing, and practically important problem. The dominant
paradigm is dispersion within the dynamical context of a nondivergent flow:
objects initially close together will on average spread apart but the area of
surface patches of material does not change. Although this paradigm is likely
valid at mesoscales, larger than 100 km in horizontal scale, recent theoretical
studies of submesoscales (less than ~10 km) predict strong surface convergences
and downwelling associated with horizontal density fronts and cyclonic vortices.
Here we show that such structures can dramatically concentrate floating material.
More than half of an array of ~200 surface drifters covering ~20 * 20 km2
converged into a 60 * 60 m region within a week, a factor of more than 105
decrease in area, before slowly dispersing. As predicted, the convergence
occurred at density fronts and with cyclonic vorticity. A zipperlike structure
may play an important role. Cyclonic vorticity and vertical velocity reached
0.001 s-1 and 0.01 ms-1, respectively, which is much larger than usually
inferred. This suggests a paradigm in which nearby objects form submesoscale
clusters, and these clusters then spread apart. Together, these effects set both
the overall extent and the finescale texture of a patch of floating material.
Material concentrated at submesoscale convergences can create unique communities
of organisms, amplify impacts of toxic material, and create opportunities to more
efficiently recover such material.
PMID- 29339499
TI - Supercritical CO2 uptake by nonswelling phyllosilicates.
AB - Interactions between supercritical (sc) CO2 and minerals are important when CO2
is injected into geologic formations for storage and as working fluids for
enhanced oil recovery, hydraulic fracturing, and geothermal energy extraction. It
has previously been shown that at the elevated pressures and temperatures of the
deep subsurface, scCO2 alters smectites (typical swelling phyllosilicates).
However, less is known about the effects of scCO2 on nonswelling phyllosilicates
(illite and muscovite), despite the fact that the latter are the dominant clay
minerals in deep subsurface shales and mudstones. Our studies conducted by using
single crystals, combining reaction (incubation with scCO2), visualization
[atomic force microscopy (AFM)], and quantifications (AFM, X-ray photoelectron
spectroscopy, X-ray diffraction, and off-gassing measurements) revealed
unexpectedly high CO2 uptake that far exceeded its macroscopic surface area.
Results from different methods collectively suggest that CO2 partially entered
the muscovite interlayers, although the pathways remain to be determined. We
hypothesize that preferential dissolution at weaker surface defects and frayed
edges allows CO2 to enter the interlayers under elevated pressure and
temperature, rather than by diffusing solely from edges deeply into interlayers.
This unexpected uptake of CO2, can increase CO2 storage capacity by up to ~30%
relative to the capacity associated with residual trapping in a 0.2-porosity
sandstone reservoir containing up to 18 mass % of illite/muscovite. This excess
CO2 uptake constitutes a previously unrecognized potential trapping mechanism.
PMID- 29339498
TI - MAFA missense mutation causes familial insulinomatosis and diabetes mellitus.
AB - The beta-cell-enriched MAFA transcription factor plays a central role in
regulating glucose-stimulated insulin secretion while also demonstrating
oncogenic transformation potential in vitro. No disease-causing MAFA variants
have been previously described. We investigated a large pedigree with autosomal
dominant inheritance of diabetes mellitus or insulinomatosis, an adult-onset
condition of recurrent hyperinsulinemic hypoglycemia caused by multiple insulin
secreting neuroendocrine tumors of the pancreas. Using exome sequencing, we
identified a missense MAFA mutation (p.Ser64Phe, c.191C>T) segregating with both
phenotypes of insulinomatosis and diabetes. This mutation was also found in a
second unrelated family with the same clinical phenotype, while no germline or
somatic MAFA mutations were identified in nine patients with sporadic
insulinomatosis. In the two families, insulinomatosis presented more frequently
in females (eight females/two males) and diabetes more often in males (12
males/four females). Four patients from the index family, including two
homozygotes, had a history of congenital cataract and/or glaucoma. The p.Ser64Phe
mutation was found to impair phosphorylation within the transactivation domain of
MAFA and profoundly increased MAFA protein stability under both high and low
glucose concentrations in beta-cell lines. In addition, the transactivation
potential of p.Ser64Phe MAFA in beta-cell lines was enhanced compared with wild
type MAFA. In summary, the p.Ser64Phe missense MAFA mutation leads to familial
insulinomatosis or diabetes by impacting MAFA protein stability and
transactivation ability. The human phenotypes associated with the p.Ser64Phe MAFA
missense mutation reflect both the oncogenic capacity of MAFA and its key role in
islet beta-cell activity.
PMID- 29339501
TI - Correction to Supporting Information for Carlson et al., Effect of oil palm
sustainability certification on deforestation and fire in Indonesia.
PMID- 29339500
TI - Regulation of the stability of RGF1 receptor by the ubiquitin-specific proteases
UBP12/UBP13 is critical for root meristem maintenance.
AB - ROOT MERISTEM GROWTH FACTOR (RGF) 1 is an important peptide hormone that
regulates root growth. Upon binding to its receptor, RGFR1, RGF1 regulates the
expression of two transcription factors, PLETHORA 1 and 2 (PLT1/2), to influence
root meristem development. Here, we show that the ubiquitin-specific proteases
UBP12 and UBP13 are positive regulators of root meristem development and that
UBP13 interacts directly with RGF1 receptor (RGFR1) and its close homolog RGFR2.
The ubp12,13 double-mutant root is completely insensitive to exogenous applied
RGF1. Consistent with this result, RGF1-induced ubiquitination and turnover of
RGFR1 protein were accelerated in ubp12,13-mutant plants but were delayed in
transgenic plants overexpressing UBP13 Genetic analysis showed that PLT2 or RGFR1
overexpression partially rescued the short-root phenotype and the reduced
cortical root meristem cell number in ubp12,13 plants. Together, our results
demonstrate that UBP12/13 are regulators of the RGF1-RGFR1-PLT1/2 signaling
pathway and that UBP12/13 can counteract RGF1-induced RGFR1 ubiquitination,
stabilize RGFR1, and maintain root cell sensitivity to RGF1.
PMID- 29339502
TI - Protein aggregation of the p63 transcription factor underlies severe skin
fragility in AEC syndrome.
AB - The p63 gene encodes a master regulator of epidermal commitment, development, and
differentiation. Heterozygous mutations in the C-terminal domain of the p63 gene
can cause ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, a
life-threatening disorder characterized by skin fragility and severe, long
lasting skin erosions. Despite deep knowledge of p63 functions, little is known
about mechanisms underlying disease pathology and possible treatments. Here, we
show that multiple AEC-associated p63 mutations, but not those causative of other
diseases, lead to thermodynamic protein destabilization, misfolding, and
aggregation, similar to the known p53 gain-of-function mutants found in cancer.
AEC mutant proteins exhibit impaired DNA binding and transcriptional activity,
leading to dominant negative effects due to coaggregation with wild-type p63 and
p73. Importantly, p63 aggregation occurs also in a conditional knock-in mouse
model for the disorder, in which the misfolded p63 mutant protein leads to severe
epidermal defects. Variants of p63 that abolish aggregation of the mutant
proteins are able to rescue p63's transcriptional function in reporter assays as
well as in a human fibroblast-to-keratinocyte conversion assay. Our studies
reveal that AEC syndrome is a protein aggregation disorder and opens avenues for
therapeutic intervention.
PMID- 29339503
TI - Heteromeric interactions regulate butyrophilin (BTN) and BTN-like molecules
governing gammadelta T cell biology.
AB - The long-held view that gamma delta (gammadelta) T cells in mice and humans are
fundamentally dissimilar, as are gammadelta cells in blood and peripheral
tissues, has been challenged by emerging evidence of the cells' regulation by
butyrophilin (BTN) and butyrophilin-like (BTNL) molecules. Thus, murine Btnl1 and
the related gene, Skint1, mediate T cell receptor (TCR)-dependent selection of
murine intraepithelial gammadelta T cell repertoires in gut and skin,
respectively; BTNL3 and BTNL8 are TCR-dependent regulators of human gut
gammadelta cells; and BTN3A1 is essential for TCR-dependent activation of human
peripheral blood Vgamma9Vdelta2+ T cells. However, some observations concerning
BTN/Btnl molecules continue to question the extent of mechanistic conservation.
In particular, murine and human gut gammadelta cell regulation depends on
pairings of Btnl1 and Btnl6 and BTNL3 and BTNL8, respectively, whereas blood
gammadelta cells are reported to be regulated by BTN3A1 independent of other
BTNs. Addressing this paradox, we show that BTN3A2 regulates the subcellular
localization of BTN3A1, including functionally important associations with the
endoplasmic reticulum (ER), and is specifically required for optimal BTN3A1
mediated activation of Vgamma9Vdelta2+ T cells. Evidence that BTNL3/BTNL8 and
Btnl1/Btnl6 likewise associate with the ER reinforces the prospect of broadly
conserved mechanisms underpinning the selection and activation of gammadelta
cells in mice and humans, and in blood and extralymphoid sites.
PMID- 29339504
TI - Complement pathway gene activation and rising circulating immune complexes
characterize early disease in HIV-associated tuberculosis.
AB - The transition between latent and active tuberculosis (TB) occurs before symptom
onset. Better understanding of the early events in subclinical disease will
facilitate the development of diagnostics and interventions that improve TB
control. This is particularly relevant in the context of HIV-1 coinfection where
progression of TB is more likely. In a recent study using [18F]-fluoro-2-deoxy-d
glucose positron emission/computed tomography (FDG-PET/CT) on 35 asymptomatic,
HIV-1-infected adults, we identified 10 participants with radiographic evidence
of subclinical disease, significantly more likely to progress than the 25
participants without. To gain insight into the biological events in early
disease, we performed blood-based whole genome transcriptomic analysis on these
participants and 15 active patients with TB. We found transcripts representing
the classical complement pathway and Fcgamma receptor 1 overabundant from
subclinical stages of disease. Levels of circulating immune (antibody/antigen)
complexes also increased in subclinical disease and were highly correlated with
C1q transcript abundance. To validate our findings, we analyzed transcriptomic
data from a publicly available dataset where samples were available in the 2 y
before TB disease presentation. Transcripts representing the classical complement
pathway and Fcgamma receptor 1 were also differentially expressed in the 12 mo
before disease presentation. Our results indicate that levels of antibody/antigen
complexes increase early in disease, associated with increased gene expression of
C1q and Fcgamma receptors that bind them. Understanding the role this plays in
disease progression may facilitate development of interventions that prevent
this, leading to a more favorable outcome and may also be important to diagnostic
development.
PMID- 29339505
TI - Nonenzymatic release of N7-methylguanine channels repair of abasic sites into an
AP endonuclease-independent pathway in Arabidopsis.
AB - Abasic (apurinic/apyrimidinic, AP) sites in DNA arise from spontaneous base loss
or by enzymatic removal during base excision repair. It is commonly accepted that
both classes of AP site have analogous biochemical properties and are equivalent
substrates for AP endonucleases and AP lyases, although the relative roles of
these two types of enzymes are not well understood. We provide here genetic and
biochemical evidence that, in Arabidopsis, AP sites generated by spontaneous loss
of N7-methylguanine (N7-meG) are exclusively repaired through an AP endonuclease
independent pathway initiated by FPG, a bifunctional DNA glycosylase with AP
lyase activity. Abasic site incision catalyzed by FPG generates a single
nucleotide gap with a 3'-phosphate terminus that is processed by the DNA 3'
phosphatase ZDP before repair is completed. We further show that the major AP
endonuclease in Arabidopsis (ARP) incises AP sites generated by enzymatic N7-meG
excision but, unexpectedly, not those resulting from spontaneous N7-meG loss.
These findings, which reveal previously undetected differences between products
of enzymatic and nonenzymatic base release, may shed light on the evolution and
biological roles of AP endonucleases and AP lyases.
PMID- 29339506
TI - Development and retention of a primordial moonlighting pathway of protein
modification in the absence of selection presents a puzzle.
AB - Lipoic acid is synthesized by a remarkably atypical pathway in which the cofactor
is assembled on its cognate proteins. An octanoyl moiety diverted from fatty acid
synthesis is covalently attached to the acceptor protein, and sulfur insertion at
carbons 6 and 8 of the octanoyl moiety form the lipoyl cofactor. Covalent
attachment of this cofactor is required for function of several central
metabolism enzymes, including the glycine cleavage H protein (GcvH). In Bacillus
subtilis, GcvH is the sole substrate for lipoate assembly. Hence lipoic acid
requiring 2-oxoacid dehydrogenase (OADH) proteins acquire the cofactor only by
transfer from lipoylated GcvH. Lipoyl transfer has been argued to be the
primordial pathway of OADH lipoylation. The Escherichia coli pathway where
lipoate is directly assembled on both its GcvH and OADH proteins, is proposed to
have arisen later. Because roughly 3 billion years separate the divergence of
these bacteria, it is surprising that E. coli GcvH functionally substitutes for
the B. subtilis protein in lipoyl transfer. Known and putative GcvHs from other
bacteria and eukaryotes also substitute for B. subtilis GcvH in OADH
modification. Because glycine cleavage is the primary GcvH role in ancestral
bacteria that lack OADH enzymes, lipoyl transfer is a "moonlighting" function:
that is, development of a new function while retaining the original function.
This moonlighting has been conserved in the absence of selection by some, but not
all, GcvH proteins. Moreover, Aquifex aeolicus encodes five putative GcvHs, two
of which have the moonlighting function, whereas others function only in glycine
cleavage.
PMID- 29339508
TI - Human ectoparasites and the spread of plague in Europe during the Second
Pandemic.
AB - Plague, caused by the bacterium Yersinia pestis, can spread through human
populations by multiple transmission pathways. Today, most human plague cases are
bubonic, caused by spillover of infected fleas from rodent epizootics, or
pneumonic, caused by inhalation of infectious droplets. However, little is known
about the historical spread of plague in Europe during the Second Pandemic (14
19th centuries), including the Black Death, which led to high mortality and
recurrent epidemics for hundreds of years. Several studies have suggested that
human ectoparasite vectors, such as human fleas (Pulex irritans) or body lice
(Pediculus humanus humanus), caused the rapidly spreading epidemics. Here, we
describe a compartmental model for plague transmission by a human ectoparasite
vector. Using Bayesian inference, we found that this model fits mortality curves
from nine outbreaks in Europe better than models for pneumonic or rodent
transmission. Our results support that human ectoparasites were primary vectors
for plague during the Second Pandemic, including the Black Death (1346-1353),
ultimately challenging the assumption that plague in Europe was predominantly
spread by rats.
PMID- 29339507
TI - Large-scale comparative epigenomics reveals hierarchical regulation of non-CG
methylation in Arabidopsis.
AB - Genome-wide characterization by next-generation sequencing has greatly improved
our understanding of the landscape of epigenetic modifications. Since 2008, whole
genome bisulfite sequencing (WGBS) has become the gold standard for DNA
methylation analysis, and a tremendous amount of WGBS data has been generated by
the research community. However, the systematic comparison of DNA methylation
profiles to identify regulatory mechanisms has yet to be fully explored. Here we
reprocessed the raw data of over 500 publicly available Arabidopsis WGBS
libraries from various mutant backgrounds, tissue types, and stress treatments
and also filtered them based on sequencing depth and efficiency of bisulfite
conversion. This enabled us to identify high-confidence differentially methylated
regions (hcDMRs) by comparing each test library to over 50 high-quality wild-type
controls. We developed statistical and quantitative measurements to analyze the
overlapping of DMRs and to cluster libraries based on their effect on DNA
methylation. In addition to confirming existing relationships, we revealed
unanticipated connections between well-known genes. For instance, MET1 and CMT3
were found to be required for the maintenance of asymmetric CHH methylation at
nonoverlapping regions of CMT2 targeted heterochromatin. Our comparative
methylome approach has established a framework for extracting biological insights
via large-scale comparison of methylomes and can also be adopted for other
genomics datasets.
PMID- 29339509
TI - Biodegradable Piezoelectric Force Sensor.
AB - Measuring vital physiological pressures is important for monitoring health
status, preventing the buildup of dangerous internal forces in impaired organs,
and enabling novel approaches of using mechanical stimulation for tissue
regeneration. Pressure sensors are often required to be implanted and directly
integrated with native soft biological systems. Therefore, the devices should be
flexible and at the same time biodegradable to avoid invasive removal surgery
that can damage directly interfaced tissues. Despite recent achievements in
degradable electronic devices, there is still a tremendous need to develop a
force sensor which only relies on safe medical materials and requires no complex
fabrication process to provide accurate information on important biophysiological
forces. Here, we present a strategy for material processing, electromechanical
analysis, device fabrication, and assessment of a piezoelectric Poly-l-lactide
(PLLA) polymer to create a biodegradable, biocompatible piezoelectric force
sensor, which only employs medical materials used commonly in Food and Drug
Administration-approved implants, for the monitoring of biological forces. We
show the sensor can precisely measure pressures in a wide range of 0-18 kPa and
sustain a reliable performance for a period of 4 d in an aqueous environment. We
also demonstrate this PLLA piezoelectric sensor can be implanted inside the
abdominal cavity of a mouse to monitor the pressure of diaphragmatic contraction.
This piezoelectric sensor offers an appealing alternative to present
biodegradable electronic devices for the monitoring of intraorgan pressures. The
sensor can be integrated with tissues and organs, forming self-sensing bionic
systems to enable many exciting applications in regenerative medicine, drug
delivery, and medical devices.
PMID- 29339510
TI - Artificial intelligence exploration of unstable protocells leads to predictable
properties and discovery of collective behavior.
AB - Protocell models are used to investigate how cells might have first assembled on
Earth. Some, like oil-in-water droplets, can be seemingly simple models, while
able to exhibit complex and unpredictable behaviors. How such simple oil-in-water
systems can come together to yield complex and life-like behaviors remains a key
question. Herein, we illustrate how the combination of automated experimentation
and image processing, physicochemical analysis, and machine learning allows
significant advances to be made in understanding the driving forces behind oil-in
water droplet behaviors. Utilizing >7,000 experiments collected using an
autonomous robotic platform, we illustrate how smart automation cannot only help
with exploration, optimization, and discovery of new behaviors, but can also be
core to developing fundamental understanding of such systems. Using this process,
we were able to relate droplet formulation to behavior via predicted physical
properties, and to identify and predict more occurrences of a rare collective
droplet behavior, droplet swarming. Proton NMR spectroscopic and qualitative pH
methods enabled us to better understand oil dissolution, chemical change, phase
transitions, and droplet and aqueous phase flows, illustrating the utility of the
combination of smart-automation and traditional analytical chemistry techniques.
We further extended our study for the simultaneous exploration of both the oil
and aqueous phases using a robotic platform. Overall, this work shows that the
combination of chemistry, robotics, and artificial intelligence enables
discovery, prediction, and mechanistic understanding in ways that no one approach
could achieve alone.
PMID- 29339511
TI - The role of obesity in exceptionally slow US mortality improvement.
AB - Recent studies have described a reduction in the rate of improvement in American
mortality. The pace of improvement is also slow by international standards. This
paper attempts to identify the extent to which rising body mass index (BMI) is
responsible for reductions in the rate of mortality improvement in the United
States. The data for this study were obtained from subsequent cohorts of the
National Health and Nutrition Examination Survey (NHANES III, 1988-1994; NHANES
continuous, 1999-2010) and from the NHANES linked mortality files, which include
follow-up into death records through December 2011. The role of BMI was estimated
using Cox models comparing mortality trends in the presence and absence of
adjustment for maximum lifetime BMI (Max BMI). Introducing Max BMI into a Cox
model controlling for age and sex raised the annual rate of mortality decline by
0.54% (95% confidence interval 0.45-0.64%). Results were robust to the inclusion
of other variables in the model, to differences in how Max BMI was measured, and
to how trends were evaluated. The effect of rising Max BMI is large relative to
international mortality trends and to alternative mortality futures simulated by
the Social Security Administration. The increase in Max BMI over the period 1988
2011 is estimated to have reduced life expectancy at age 40 by 0.9 years in 2011
(95% confidence interval 0.7-1.1 years) and accounted for 186,000 excess deaths
that year. Rising levels of BMI have prevented the United States from enjoying
the full benefits of factors working to improve mortality.
PMID- 29339512
TI - Neural preservation underlies speech improvement from auditory deprivation in
young cochlear implant recipients.
AB - Although cochlear implantation enables some children to attain age-appropriate
speech and language development, communicative delays persist in others, and
outcomes are quite variable and difficult to predict, even for children implanted
early in life. To understand the neurobiological basis of this variability, we
used presurgical neural morphological data obtained from MRI of individual
pediatric cochlear implant (CI) candidates implanted younger than 3.5 years to
predict variability of their speech-perception improvement after surgery. We
first compared neuroanatomical density and spatial pattern similarity of CI
candidates to that of age-matched children with normal hearing, which allowed us
to detail neuroanatomical networks that were either affected or unaffected by
auditory deprivation. This information enables us to build machine-learning
models to predict the individual children's speech development following CI. We
found that regions of the brain that were unaffected by auditory deprivation, in
particular the auditory association and cognitive brain regions, produced the
highest accuracy, specificity, and sensitivity in patient classification and the
most precise prediction results. These findings suggest that brain areas
unaffected by auditory deprivation are critical to developing closer to typical
speech outcomes. Moreover, the findings suggest that determination of the type of
neural reorganization caused by auditory deprivation before implantation is
valuable for predicting post-CI language outcomes for young children.
PMID- 29339513
TI - Projecting one's own spatial bias onto others during a theory-of-mind task.
AB - Many people show a left-right bias in visual processing. We measured spatial bias
in neurotypical participants using a variant of the line bisection task. In the
same participants, we measured performance in a social cognition task. This
theory-of-mind task measured whether each participant had a processing-speed bias
toward the right of, or left of, a cartoon agent about which the participant was
thinking. Crucially, the cartoon was rotated such that what was left and right
with respect to the cartoon was up and down with respect to the participant.
Thus, a person's own left-right bias could not align directly onto left and right
with respect to the cartoon head. Performance on the two tasks was significantly
correlated. People who had a natural bias toward processing their own left side
of space were quicker to process how the cartoon might think about objects to the
left side of its face, and likewise for a rightward bias. One possible
interpretation of these results is that the act of processing one's own personal
space shares some of the same underlying mechanisms as the social cognitive act
of reconstructing someone else's processing of their space.
PMID- 29339514
TI - Flexibility of thought in high creative individuals represented by percolation
analysis.
AB - Flexibility of thought is theorized to play a critical role in the ability of
high creative individuals to generate novel and innovative ideas. However, this
has been examined only through indirect behavioral measures. Here we use network
percolation analysis (removal of links in a network whose strength is below an
increasing threshold) to computationally examine the robustness of the semantic
memory networks of low and high creative individuals. Robustness of a network
indicates its flexibility and thus can be used to quantify flexibility of thought
as related to creativity. This is based on the assumption that the higher the
robustness of the semantic network, the higher its flexibility. Our analysis
reveals that the semantic network of high creative individuals is more robust to
network percolation compared with the network of low creative individuals and
that this higher robustness is related to differences in the structure of the
networks. Specifically, we find that this higher robustness is related to
stronger links connecting between different components of similar semantic words
in the network, which may also help to facilitate spread of activation over their
network. Thus, we directly and quantitatively examine the relation between
flexibility of thought and creative ability. Our findings support the associative
theory of creativity, which posits that high creative ability is related to a
flexible structure of semantic memory. Finally, this approach may have further
implications, by enabling a quantitative examination of flexibility of thought,
in both healthy and clinical populations.
PMID- 29339515
TI - MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the
epigenetic landscape.
AB - Convergent evolution dictates that diverse groups of viruses will target both
similar and distinct host pathways to manipulate the immune response and improve
infection. In this study, we sought to leverage this uneven viral antagonism to
identify critical host factors that govern disease outcome. Utilizing a systems
based approach, we examined differential regulation of IFN-gamma-dependent genes
following infection with robust respiratory viruses including influenza viruses
[A/influenza/Vietnam/1203/2004 (H5N1-VN1203) and A/influenza/California/04/2009
(H1N1-CA04)] and coronaviruses [severe acute respiratory syndrome coronavirus
(SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV)]. Categorizing by
function, we observed down-regulation of gene expression associated with antigen
presentation following both H5N1-VN1203 and MERS-CoV infection. Further
examination revealed global down-regulation of antigen-presentation gene
expression, which was confirmed by proteomics for both H5N1-VN1203 and MERS-CoV
infection. Importantly, epigenetic analysis suggested that DNA methylation,
rather than histone modification, plays a crucial role in MERS-CoV-mediated
antagonism of antigen-presentation gene expression; in contrast, H5N1-VN1203
likely utilizes a combination of epigenetic mechanisms to target antigen
presentation. Together, the results indicate a common mechanism utilized by H5N1
VN1203 and MERS-CoV to modulate antigen presentation and the host adaptive immune
response.
PMID- 29339516
TI - Human airway branch variation and chronic obstructive pulmonary disease.
AB - Susceptibility to chronic obstructive pulmonary disease (COPD) beyond cigarette
smoking is incompletely understood, although several genetic variants associated
with COPD are known to regulate airway branch development. We demonstrate that in
vivo central airway branch variants are present in 26.5% of the general
population, are unchanged over 10 y, and exhibit strong familial aggregation. The
most common airway branch variant is associated with COPD in two cohorts (n =
5,054), with greater central airway bifurcation density, and with emphysema
throughout the lung. The second most common airway branch variant is associated
with COPD among smokers, with narrower airway lumens in all lobes, and with
genetic polymorphisms within the FGF10 gene. We conclude that central airway
branch variation, readily detected by computed tomography, is a biomarker of
widely altered lung structure with a genetic basis and represents a COPD
susceptibility factor.
PMID- 29339517
TI - Infected erythrocytes expressing DC13 PfEMP1 differ from recombinant proteins in
EPCR-binding function.
AB - Recent advances have identified a new paradigm for cerebral malaria pathogenesis
in which endothelial protein C receptor (EPCR) is a major host receptor for
sequestration of Plasmodium falciparum-infected erythrocytes (IEs) in the brain
and other vital organs. The parasite adhesins that bind EPCR are members of the
IE variant surface antigen family Plasmodium falciparum erythrocyte membrane
protein 1 (PfEMP1) containing specific adhesion domains called domain cassette
(DC) 8 and DC13. The binding interaction site between PfEMP1 and EPCR has been
mapped by biophysical and crystallography studies using recombinant proteins.
However, studies examining the interaction of native PfEMP1 on the IE surface
with EPCR are few. We aimed to study binding to EPCR by IEs expressing DC8 and
DC13 PfEMP1 variants whose recombinant proteins have been used in key prior
functional and structural studies. IE binding to EPCR immobilized on plastic and
on human brain endothelial cells was examined in static and flow adhesion assays.
Unexpectedly, we found that IEs expressing the DC13 PfEMP1 variant HB3var03 or
IT4var07 did not bind to EPCR on plastic and the binding of these variants to
brain endothelial cells was not dependent on EPCR. IEs expressing the DC8 variant
IT4var19 did bind to EPCR, but this interaction was inhibited if normal human
serum or plasma was present, raising the possibility that IE-EPCR interaction may
be prevented by plasma components under physiological conditions. These data
highlight a discrepancy in EPCR-binding activity between PfEMP1 recombinant
proteins and IEs, and indicate the critical need for further research to
understand the pathophysiological significance of the PfEMP1-EPCR interaction.
PMID- 29339518
TI - Iterative optimization yields Mcl-1-targeting stapled peptides with selective
cytotoxicity to Mcl-1-dependent cancer cells.
AB - Bcl-2 family proteins regulate apoptosis, and aberrant interactions of
overexpressed antiapoptotic family members such as Mcl-1 promote cell
transformation, cancer survival, and resistance to chemotherapy. Discovering
potent and selective Mcl-1 inhibitors that can relieve apoptotic blockades is
thus a high priority for cancer research. An attractive strategy for disabling
Mcl-1 involves using designer peptides to competitively engage its binding
groove, mimicking the structural mechanism of action of native sensitizer BH3
only proteins. We transformed Mcl-1-binding peptides into alpha-helical, cell
penetrating constructs that are selectively cytotoxic to Mcl-1-dependent cancer
cells. Critical to the design of effective inhibitors was our introduction of an
all-hydrocarbon cross-link or "staple" that stabilizes alpha-helical structure,
increases target binding affinity, and independently confers binding specificity
for Mcl-1 over related Bcl-2 family paralogs. Two crystal structures of complexes
at 1.4 A and 1.9 A resolution demonstrate how the hydrophobic staple induces an
unanticipated structural rearrangement in Mcl-1 upon binding. Systematic sampling
of staple location and iterative optimization of peptide sequence in accordance
with established design principles provided peptides that target intracellular
Mcl-1. This work provides proof of concept for the development of potent,
selective, and cell-permeable stapled peptides for therapeutic targeting of Mcl-1
in cancer, applying a design and validation workflow applicable to a host of
challenging biomedical targets.
PMID- 29339519
TI - Evidence for convergent evolution of SINE-directed Staufen-mediated mRNA decay.
AB - Primate-specific Alu short interspersed elements (SINEs) as well as rodent
specific B and ID (B/ID) SINEs can promote Staufen-mediated decay (SMD) when
present in mRNA 3'-untranslated regions (3'-UTRs). The transposable nature of
SINEs, their presence in long noncoding RNAs, their interactions with Staufen,
and their rapid divergence in different evolutionary lineages suggest they could
have generated substantial modification of posttranscriptional gene-control
networks during mammalian evolution. Some of the variation in SMD regulation
produced by SINE insertion might have had a similar regulatory effect in separate
mammalian lineages, leading to parallel evolution of the Staufen network by
independent expansion of lineage-specific SINEs. To explore this possibility, we
searched for orthologous gene pairs, each carrying a species-specific 3'-UTR SINE
and each regulated by SMD, by measuring changes in mRNA abundance after
individual depletion of two SMD factors, Staufen1 (STAU1) and UPF1, in both human
and mouse myoblasts. We identified and confirmed orthologous gene pairs with 3'
UTR SINEs that independently function in SMD control of myoblast metabolism.
Expanding to other species, we demonstrated that SINE-directed SMD likely emerged
in both primate and rodent lineages >20-25 million years ago. Our work reveals a
mechanism for the convergent evolution of posttranscriptional gene regulatory
networks in mammals by species-specific SINE transposition and SMD.
PMID- 29339520
TI - Targeted knockout of a chemokine-like gene increases anxiety and fear responses.
AB - Emotional responses, such as fear and anxiety, are fundamentally important
behavioral phenomena with strong fitness components in most animal species.
Anxiety-related disorders continue to represent a major unmet medical need in our
society, mostly because we still do not fully understand the mechanisms of these
diseases. Animal models may speed up discovery of these mechanisms. The zebrafish
is a highly promising model organism in this field. Here, we report the
identification of a chemokine-like gene family, samdori (sam), and present
functional characterization of one of its members, sam2 We show exclusive mRNA
expression of sam2 in the CNS, predominantly in the dorsal habenula,
telencephalon, and hypothalamus. We found knockout (KO) zebrafish to exhibit
altered anxiety-related responses in the tank, scototaxis and shoaling assays,
and increased crh mRNA expression in their hypothalamus compared with wild-type
fish. To investigate generalizability of our findings to mammals, we developed a
Sam2 KO mouse and compared it to wild-type littermates. Consistent with zebrafish
findings, homozygous KO mice exhibited signs of elevated anxiety. We also found
bath application of purified SAM2 protein to increase inhibitory postsynaptic
transmission onto CRH neurons of the paraventricular nucleus. Finally, we
identified a human homolog of SAM2, and were able to refine a candidate gene
region encompassing SAM2, among 21 annotated genes, which is associated with
intellectual disability and autism spectrum disorder in the 12q14.1 deletion
syndrome. Taken together, these results suggest a crucial and evolutionarily
conserved role of sam2 in regulating mechanisms associated with anxiety.
PMID- 29339521
TI - Immunogenetic novelty confers a selective advantage in host-pathogen coevolution.
AB - The major histocompatibility complex (MHC) is crucial to the adaptive immune
response of vertebrates and is among the most polymorphic gene families known.
Its high diversity is usually attributed to selection imposed by fast-evolving
pathogens. Pathogens are thought to evolve to escape recognition by common immune
alleles, and, hence, novel MHC alleles, introduced through mutation,
recombination, or gene flow, are predicted to give hosts superior resistance.
Although this theoretical prediction underpins host-pathogen "Red Queen"
coevolution, it has not been demonstrated in the context of natural MHC
diversity. Here, we experimentally tested whether novel MHC variants (both
alleles and functional "supertypes") increased resistance of guppies (Poecilia
reticulata) to a common ectoparasite (Gyrodactylus turnbulli). We used exposure
controlled infection trials with wild-sourced parasites, and Gyrodactylus-naive
host fish that were F2 descendants of crossed wild populations. Hosts carrying
MHC variants (alleles or supertypes) that were new to a given parasite population
experienced a 35-37% reduction in infection intensity, but the number of MHC
variants carried by an individual, analogous to heterozygosity in single-locus
systems, was not a significant predictor. Our results provide direct evidence of
novel MHC variant advantage, confirming a fundamental mechanism underpinning the
exceptional polymorphism of this gene family and highlighting the role of
immunogenetic novelty in host-pathogen coevolution.
PMID- 29339523
TI - DNA synthesis from diphosphate substrates by DNA polymerases.
AB - The activity of DNA polymerase underlies numerous biotechnologies, cell division,
and therapeutics, yet the enzyme remains incompletely understood. We demonstrate
that both thermostable and mesophilic DNA polymerases readily utilize
deoxyribonucleoside diphosphates (dNDPs) for DNA synthesis and inorganic
phosphate for the reverse reaction, that is, phosphorolysis of DNA. For Taq DNA
polymerase, the KMs of the dNDP and phosphate substrates are ~20 and 200 times
higher than for dNTP and pyrophosphate, respectively. DNA synthesis from dNDPs is
about 17 times slower than from dNTPs, and DNA phosphorolysis about 200 times
less efficient than pyrophosphorolysis. Such parameters allow DNA replication
without requiring coupled metabolism to sequester the phosphate products, which
consequently do not pose a threat to genome stability. This mechanism contrasts
with DNA synthesis from dNTPs, which yield high-energy pyrophosphates that have
to be hydrolyzed to phosphates to prevent the reverse reaction. Because the last
common ancestor was likely a thermophile, dNDPs are plausible substrates for
genome replication on early Earth and may represent metabolic intermediates later
replaced by the higher-energy triphosphates.
PMID- 29339522
TI - Effect of beta-agonists on LAM progression and treatment.
AB - Lymphangioleiomyomatosis (LAM), a rare disease of women, is associated with
cystic lung destruction resulting from the proliferation of abnormal smooth
muscle-like LAM cells with mutations in the tuberous sclerosis complex (TSC)
genes TSC1 and/or TSC2 The mutant genes and encoded proteins are responsible for
activation of the mechanistic target of rapamycin (mTOR), which is inhibited by
sirolimus (rapamycin), a drug used to treat LAM. Patients who have LAM may also
be treated with bronchodilators for asthma-like symptoms due to LAM. We observed
stabilization of forced expiratory volume in 1 s over time in patients receiving
sirolimus and long-acting beta-agonists with short-acting rescue inhalers
compared with patients receiving only sirolimus. Because beta-agonists increase
cAMP and PKA activity, we investigated effects of PKA activation on the mTOR
pathway. Human skin TSC2+/- fibroblasts or LAM lung cells incubated short-term
with isoproterenol (beta-agonist) showed a sirolimus-independent increase in
phosphorylation of S6, a downstream effector of the mTOR pathway, and increased
cell growth. Cells incubated long-term with isoproterenol, which may lead to beta
adrenergic receptor desensitization, did not show increased S6 phosphorylation.
Inhibition of PKA blocked the isoproterenol effect on S6 phosphorylation. Thus,
activation of PKA by beta-agonists increased phospho-S6 independent of mTOR, an
effect abrogated by beta-agonist-driven receptor desensitization. In agreement,
retrospective clinical data from patients with LAM suggested that a combination
of bronchodilators in conjunction with sirolimus may be preferable to sirolimus
alone for stabilization of pulmonary function.
PMID- 29339524
TI - Communication in context: Interpreting promises in an experiment on competition
and trust.
AB - How much do people lie, and how much do people trust communication when lying is
possible? An important step toward answering these questions is understanding how
communication is interpreted. This paper establishes in a canonical experiment
that competition can alter the shared communication code: the commonly understood
meaning of messages. We study a sender-receiver game in which the sender dictates
how to share $10 with the receiver, if the receiver participates. The receiver
has an outside option and decides whether to participate after receiving a
nonbinding offer from the sender. Competition for play between senders leads to
higher offers but has no effect on actual transfers, expected transfers, or
receivers' willingness to play. The higher offers signal that sharing will be
equitable without the expectation that they should be followed literally: Under
competition "6 is the new 5."
PMID- 29339525
TI - Pulsating dissolution of crystalline matter.
AB - Fluid-solid reactions result in material flux from or to the solid surface. The
prediction of the flux, its variations, and changes with time are of interest to
a wide array of disciplines, ranging from the material and earth sciences to
pharmaceutical sciences. Reaction rate maps that are derived from sequences of
topography maps illustrate the spatial distribution of reaction rates across the
crystal surface. Here, we present highly spatially resolved rate maps that reveal
the existence of rhythmic pulses of the material flux from the crystal surface.
This observation leads to a change in our understanding of the way crystalline
matter dissolves. Rhythmic fluctuations of the reactive surface site density and
potentially concomitant oscillations in the fluid saturation imply spatial and
temporal variability in surface reaction rates. Knowledge of such variability
could aid attempts to upscale microscopic rates and predict reactive transport
through changing porous media.
PMID- 29339526
TI - The diversity of gestational diabetes: a therapeutic challenge.
AB - Metformin as the first drug of choice for glucose lowering in gestational
diabetes (GDM) is still controversial, despite recent publications reporting
similar outcomes in comparison to insulin, both for offspring and mothers. The
use of metformin during pregnancy is increasing and several recent guidelines
recommend metformin use in GDM pregnancies. Background, current metformin use and
unresolved concerns are discussed in the context of the article from Gante and
coworkers.
PMID- 29339527
TI - Diminished androgen and estrogen receptors and aromatase levels in hypogonadal
diabetic men: reversal with testosterone.
AB - AIMS: One-third of males with type 2 diabetes (T2DM) have hypogonadism,
characterized by low total and free testosterone concentrations. We hypothesized
that this condition is associated with a compensatory increase in the expression
of androgen receptors (AR) and that testosterone replacement reverses these
changes. We also measured estrogen receptor and aromatase expression. MATERIALS
AND METHODS: This is a randomized double-blind placebo-controlled trial. Thirty
two hypogonadal and 32 eugonadal men with T2DM were recruited. Hypogonadal men
were randomized to receive intramuscular testosterone or saline every 2 weeks for
22 weeks. We measured AR, ERalpha and aromatase expression in peripheral blood
mononuclear cells (MNC), adipose tissue and skeletal muscle in hypogonadal and
eugonadal males with T2DM at baseline and after 22 weeks of treatment in those
with hypogonadism. RESULTS: The mRNA expression of AR, ERalpha (ESR1) and
aromatase in adipose tissue from hypogonadal men was significantly lower as
compared to eugonadal men, and it increased significantly to levels comparable to
those in eugonadal patients with T2DM following testosterone treatment. AR mRNA
expression was also significantly lower in MNC from hypogonadal patients compared
to eugonadal T2DM patients. Testosterone administration in hypogonadal patients
also restored AR mRNA and nuclear extract protein levels from MNC to that in
eugonadal patients. In the skeletal muscle, AR mRNA and protein expression are
lower in men with hypogonadism. Testosterone treatment restored AR expression
levels to that comparable to levels in eugonadal men. CONCLUSIONS: We conclude
that, contrary to our hypothesis, the expression of AR, ERalpha and aromatase is
significantly diminished in hypogonadal men as compared to eugonadal men with
type 2 diabetes. Following testosterone replacement, there is a reversal of these
deficits.
PMID- 29339529
TI - MANAGEMENT OF ENDOCRINE DISEASE: Atypical femoral fractures: risks and benefits
of long-term treatment of osteoporosis with anti-resorptive therapy.
AB - Modern osteoporosis treatment began in the mid-1990s with the approval of amino
bisphosphonates, anti-resorptive agents that have been shown to decrease
osteoporotic fracture risk by about half. In 2005, the first cases of atypical
femoral fractures (AFF), occurring in the shaft of the femur, were reported.
Since then, more cases have been found, leading to great concern among patients
and a dramatic decrease in bisphosphonate prescribing. The pathogenesis and
incidence of AFF are reviewed herein. Management and an approach to prevention or
early detection of AFF are also provided. Denosumab, a more recently approved
anti-resorptive medication has also been associated with AFF. Long-term
management of osteoporosis and prevention of fracture are challenging in light of
this serious but uncommon side effect, yet with an aging population osteoporotic
fracture is destined to increase in frequency.
PMID- 29339528
TI - Gonadal function in adult male patients with congenital adrenal hyperplasia.
AB - CONTEXT: Current knowledge on gonadal function in congenital adrenal hyperplasia
(CAH) is mostly limited to single-center/country studies enrolling small patient
numbers. Overall data indicate that gonadal function can be compromised in men
with CAH. OBJECTIVE: To determine gonadal function in men with CAH within the
European 'dsd-LIFE' cohort. DESIGN: Cross-sectional clinical outcome study,
including retrospective data from medical records. METHODS: Fourteen academic
hospitals included 121 men with CAH aged 16-68 years. Main outcome measures were
serum hormone concentrations, semen parameters and imaging data of the testes.
RESULTS: At the time of assessment, 14/69 patients had a serum testosterone
concentration below the reference range; 7 of those were hypogonadotropic, 6
normogonadotropic and 1 hypergonadotropic. In contrast, among the patients with
normal serum testosterone (55/69), 4 were hypogonadotropic, 44 normogonadotropic
and 7 hypergonadotropic. The association of decreased testosterone with reduced
gonadotropin concentrations (odds ratio (OR) = 12.8 (2.9-57.3)) was weaker than
the association between serum androstenedione/testosterone ratio >=1 and reduced
gonadotropin concentrations (OR = 39.3 (2.1-732.4)). Evaluation of sperm quality
revealed decreased sperm concentrations (15/39), motility (13/37) and abnormal
morphology (4/28). Testicular adrenal rest tumor (TART)s were present in 39/80
patients, with a higher prevalence in patients with the most severe genotype
(14/18) and in patients with increased current 17-hydroxyprogesterone 20/35) or
androstenedione (12/18) serum concentrations. Forty-three children were fathered
by 26/113 patients. CONCLUSIONS: Men with CAH have a high risk of developing
hypothalamic-pituitary-gonadal disturbances and spermatogenic abnormalities.
Regular assessment of endocrine gonadal function and imaging for TART development
are recommended, in addition to measures for fertility protection.
PMID- 29339530
TI - MANAGEMENT OF ENDOCRINE DISEASE: Personalized medicine in the treatment of
acromegaly.
AB - Acromegaly is associated with high morbidity and elevated mortality when not
adequately treated. Surgery is the first-line treatment for most patients as it
is the only one that can lead to immediate cure. In patients who are not cured by
surgery, treatment is currently based on a trial-and-error approach. First
generation somatostatin receptor ligands (fg-SRL) are initiated for most
patients, although approximately 25% of patients present resistance to this drug
class. Some biomarkers of treatment outcome are described in the literature, with
the aim of categorizing patients into different groups to individualize their
treatments using a personalized approach. In this review, we will discuss the
current status of precision medicine for the treatment of acromegaly and future
perspectives on the use of personalized medicine for this purpose.
PMID- 29339531
TI - EMA calls for hydroxyethyl starch solutions to be taken off market.
PMID- 29339532
TI - Football headers and dementia: five minutes with Willie Stewart.
PMID- 29339533
TI - Learning-dependent chromatin remodeling highlights noncoding regulatory regions
linked to autism.
AB - Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder that is
associated with genetic risk factors. Most human disease-associated single
nucleotide polymorphisms (SNPs) are not located in genes but rather are in
regulatory regions that control gene expression. The function of regulatory
regions is determined through epigenetic mechanisms. Parallels between the
cellular basis of development and the formation of long-term memory have long
been recognized, particularly the role of epigenetic mechanisms in both
processes. We analyzed how learning alters chromatin accessibility in the mouse
hippocampus using a new high-throughput sequencing bioinformatics strategy we
call DEScan (differential enrichment scan). DEScan, which enabled the analysis of
data from epigenomic experiments containing multiple replicates, revealed changes
in chromatin accessibility at 2365 regulatory regions-most of which were
promoters. Learning-regulated promoters were active during forebrain development
in mice and were enriched in epigenetic modifications indicative of bivalent
promoters. These promoters were disproportionally intronic, showed a complex
relationship with gene expression and alternative splicing during memory
consolidation and retrieval, and were enriched in the data set relative to known
ASD risk genes. Genotyping in a clinical cohort within one of these promoters
(SHANK3 promoter 6) revealed that the SNP rs6010065 was associated with ASD. Our
data support the idea that learning recapitulates development at the epigenetic
level and demonstrate that behaviorally induced epigenetic changes in mice can
highlight regulatory regions relevant to brain disorders in patients.
PMID- 29339535
TI - Functional changes of AMPA responses in human induced pluripotent stem cell
derived neural progenitors in fragile X syndrome.
AB - Altered neuronal network formation and function involving dysregulated excitatory
and inhibitory circuits are associated with fragile X syndrome (FXS). We examined
functional maturation of the excitatory transmission system in FXS by
investigating the response of FXS patient-derived neural progenitor cells to the
glutamate analog (AMPA). Neural progenitors derived from induced pluripotent stem
cell (iPSC) lines generated from boys with FXS had augmented intracellular Ca2+
responses to AMPA and kainate that were mediated by Ca2+-permeable AMPA receptors
(CP-AMPARs) lacking the GluA2 subunit. Together with the enhanced differentiation
of glutamate-responsive cells, the proportion of CP-AMPAR and N-methyl-d
aspartate (NMDA) receptor-coexpressing cells was increased in human FXS
progenitors. Differentiation of cells lacking GluA2 was also increased and
paralleled the increased inward rectification in neural progenitors derived from
Fmr1-knockout mice (the FXS mouse model). Human FXS progenitors had increased the
expression of the precursor and mature forms of miR-181a, a microRNA that
represses translation of the transcript encoding GluA2. Blocking GluA2-lacking,
CP-AMPARs reduced the neurite length of human iPSC-derived control progenitors
and further reduced the shortened length of neurites in human FXS progenitors,
supporting the contribution of CP-AMPARs to the regulation of progenitor
differentiation. Furthermore, we observed reduced expression of Gria2 (the GluA2
encoding gene) in the frontal lobe of FXS mice, consistent with functional
changes of AMPARs in FXS. Increased Ca2+ influx through CP-AMPARs may increase
the vulnerability and affect the differentiation and migration of distinct cell
populations, which may interfere with normal circuit formation in FXS.
PMID- 29339534
TI - Inactivating mutations in Drosha mediate vascular abnormalities similar to
hereditary hemorrhagic telangiectasia.
AB - The transforming growth factor-beta (TGF-beta) and bone morphogenetic protein
(BMP) family of cytokines critically regulates vascular morphogenesis and
homeostasis. Impairment of TGF-beta or BMP signaling leads to heritable vascular
disorders, including hereditary hemorrhagic telangiectasia (HHT). Drosha, a key
enzyme for microRNA (miRNA) biogenesis, also regulates the TGF-beta and BMP
pathway through interaction with Smads and their joint control of gene expression
through miRNAs. We report that mice lacking Drosha in the vascular endothelium
developed a vascular phenotype resembling HHT that included dilated and
disorganized vasculature, arteriovenous fistulae, and hemorrhages. Exome
sequencing of HHT patients who lacked known pathogenic mutations revealed an
overrepresentation of rare nonsynonymous variants of DROSHA Two of these DROSHA
variants (P100L and R279L) did not interact with Smads and were partially
catalytically active. In zebrafish, expression of these mutants or morpholino
directed knockdown of Drosha resulted in angiogenesis defects and abnormal
vascular permeability. Together, our studies point to an essential role of Drosha
in vascular development and the maintenance of vascular integrity, and reveal a
previously unappreciated link between Drosha dysfunction and HHT.
PMID- 29339536
TI - Length of Stay and Hospital Revisit After Bacterial Tracheostomy-Associated
Respiratory Tract Infection Hospitalizations.
AB - OBJECTIVES: To identify factors associated with longer length of stay (LOS) and
higher 30-day hospital revisit rates for children hospitalized with bacterial
tracheostomy-associated respiratory tract infections (bTARTIs). METHODS: This was
a multicenter, retrospective cohort study using administrative data from the
Pediatric Health Information System database between 2007 and 2014 of patients 30
days to 17 years old with a principal discharge diagnosis of bTARTI or a
principal discharge diagnosis of bTARTI symptoms with a secondary diagnosis of
bTARTI. Primary outcomes of LOS (in days) and 30-day all-cause revisit rates
(inpatient, observation, or emergency department visit) were analyzed by using a
3-level hierarchical regression model (discharges within patients within
hospital). RESULTS: We included 3715 unique patients and 7355 discharges. The
median LOS was 4 days (interquartile range: 3-8 days), and the 30-day revisit
rate was 30.5%. Compared with children 1 to 4 years old, children aged 30 days to
12 months had both longer LOS (adjusted length of stay [aLOS] = +0.9 days; 95%
confidence interval [CI]: 0.6 to 1.3) and increased hospital revisit risk
(adjusted odds ratio [aOR] = 1.5; 95% CI: 1.3 to 1.7). Other factors associated
with longer LOS included public insurance (aLOS = +0.5 days; 95% CI: 0.2 to 0.8),
3 or more complex chronic conditions (CCCs), mechanical ventilation (acute or
chronic), and empirical anti-Pseudomonas aeruginosa antibiotics (aLOS = +0.6
days; 95% CI: 0.3 to 0.9). Other factors associated with 30-day revisit included
4 or more CCCs (aOR = 1.3; 95% CI: 1.1 to 1.6) and chronic ventilator dependency
(aOR = 1.1; 95% CI: 1.0 to 1.3). CONCLUSIONS: Ventilator-dependent patients <12
months old with at least 4 CCCs are at highest risk for both longer LOS and 30
day revisit after discharge for bTARTIs. They may benefit from bTARTI prevention
strategies and intensive care coordination while hospitalized.
PMID- 29339537
TI - STAT3/PIAS3 Levels Serve as "Early Signature" Genes in the Development of High
Grade Serous Carcinoma from the Fallopian Tube.
AB - The initial molecular events that lead to malignant transformation of the fimbria
of the fallopian tube (FT) through high-grade serous ovarian carcinoma (HGSC)
remain poorly understood. In this study, we report that increased expression of
signal transducer and activator of transcription 3 (pSTAT3 Tyr705) and
suppression or loss of protein inhibitor of activated STAT3 (PIAS3) in FT likely
drive HGSC. We evaluated human tissues-benign normal FT, tubal-peritoneal
junction (TPJ), p53 signature FT tissue, tubal intraepithelial lesion in
transition (TILT), serous tubal intraepithelial carcinoma (STIC) without ovarian
cancer, and HGSC for expression of STAT3/PIAS3 (compared with their known TP53
signature) and their target proliferation genes. We observed constitutive
activation of STAT3 and low levels or loss of PIAS3 in the TPJ, p53 signature,
TILT, and STIC through advanced stage IV (HGSC) tissues. Elevated expression of
pSTAT3 Tyr705 and decreased levels of PIAS3 appeared as early as TPJ and the
trend continued until very advanced stage HGSC (compared with high PIAS3 and low
pSTAT3 expression in normal benign FT). Exogenous expression of STAT3 in FT cells
mediated translocation of pSTAT3 and c-Myc into the nucleus. In vivo experiments
demonstrated that overexpression of STAT3 in FT secretory epithelial cells
promoted tumor progression and metastasis, mimicking the clinical disease
observed in patients with HGSC. Thus, we conclude that the STAT3 pathway plays a
role in the development and progression of HGSC from its earliest premalignant
states.Significance: Concomitant gain of pSTAT3 Tyr705 and loss of PIAS3 appear
critical for initiation and development of high-grade serous carcinoma. Cancer
Res; 78(7); 1739-50. (c)2018 AACR.
PMID- 29339538
TI - E6 Protein Expressed by High-Risk HPV Activates Super-Enhancers of the EGFR and c
MET Oncogenes by Destabilizing the Histone Demethylase KDM5C.
AB - The high-risk (HR) human papillomaviruses (HPV) are causative agents of
anogenital tract dysplasia and cancers and a fraction of head and neck cancers.
The HR HPV E6 oncoprotein possesses canonical oncogenic functions, such as p53
degradation and telomerase activation. It is also capable of stimulating
expression of several oncogenes, but the molecular mechanism underlying these
events is poorly understood. Here, we provide evidence that HPV16 E6 physically
interacts with histone H3K4 demethylase KDM5C, resulting in its degradation in an
E3 ligase E6AP- and proteasome-dependent manner. Moreover, we found that HPV16
positive cancer cell lines exhibited lower KDM5C protein levels than HPV-negative
cancer cell lines. Restoration of KDM5C significantly suppressed the
tumorigenicity of CaSki cells, an HPV16-positive cervical cancer cell line. Whole
genome ChIP-seq and RNA-seq results revealed that CaSki cells contained super
enhancers in the proto-oncogenes EGFR and c-MET Ectopic KDM5C dampened these
super-enhancers and reduced the expression of proto-oncogenes. This effect was
likely mediated by modulating H3K4me3/H3K4me1 dynamics and decreasing
bidirectional enhancer RNA transcription. Depletion of KDM5C or HPV16 E6
expression activated these two super-enhancers. These results illuminate a
pivotal relationship between the oncogenic E6 proteins expressed by HR HPV
isotypes and epigenetic activation of super-enhancers in the genome that drive
expression of key oncogenes like EGFR and c-METSignificance: This study suggests
a novel explanation for why infections with certain HPV isotypes are associated
with elevated cancer risk by identifying an epigenetic mechanism through which E6
proteins expressed by those isotypes can drive expression of key oncogenes.
Cancer Res; 78(6); 1418-30. (c)2018 AACR.
PMID- 29339539
TI - The Hippo Pathway Component TAZ Promotes Immune Evasion in Human Cancer through
PD-L1.
AB - The Hippo pathway component WW domain-containing transcription regulator 1 (TAZ)
is a transcriptional coactivator and an oncogene in breast and lung cancer.
Transcriptional targets of TAZ that modulate immune cell function in the tumor
microenvironment are poorly understood. Here, we perform a comprehensive screen
for immune-related genes regulated by TAZ and its paralog YAP using NanoString
gene expression profiling. We identify the immune checkpoint molecule PD-L1 as a
target of Hippo signaling. The upstream kinases of the Hippo pathway, mammalian
STE20-like kinase 1 and 2 (MST1/2), and large tumor suppressor 1 and 2 (LATS1/2),
suppress PD-L1 expression while TAZ and YAP enhance PD-L1 levels in breast and
lung cancer cell lines. PD-L1 expression in cancer cell lines is determined by
TAZ activity and TAZ/YAP/TEAD increase PD-L1 promoter activity. Critically, TAZ
induced PD-L1 upregulation in human cancer cells is sufficient to inhibit T-cell
function. The relationship between TAZ and PD-L1 is not conserved in multiple
mouse cell lines, likely due to differences between the human and mouse PD-L1
promoters. To explore the extent of divergence in TAZ immune-related targets
between human and mouse cells, we performed a second NanoString screen using
mouse cell lines. We show that many targets of TAZ may be differentially
regulated between these species. These findings highlight the role of Hippo
signaling in modifying human/murine physiologic/pathologic immune responses and
provide evidence implicating TAZ in human cancer immune evasion.Significance:
Human-specific activation of PD-L1 by a novel Hippo signaling pathway in cancer
immune evasion may have a significant impact on research in immunotherapy. Cancer
Res; 78(6); 1457-70. (c)2018 AACR.
PMID- 29339540
TI - Radioresistant Cervical Cancers Are Sensitive to Inhibition of Glycolysis and
Redox Metabolism.
AB - Highly glycolytic cervical cancers largely resist treatment by cisplatin and
coadministered pelvic irradiation as the present standard of care. In this study,
we investigated the effects of inhibiting glycolysis and thiol redox metabolism
to evaluate them as alternate treatment strategies in these cancers. In a panel
of multiple cervical cancer cell lines, we evaluated sensitivity to inhibition of
glycolysis (2-deoxyglucose, 2-DG) with or without simultaneous inhibition of
glutathione and thioredoxin metabolism (BSO/AUR). Intracellular levels of total
and oxidized glutathione, thioredoxin reductase activity, and indirect measures
of intracellular reactive oxygen species were compared before and after
treatment. Highly radioresistant cells were the most sensitive to 2-DG, whereas
intermediate radioresistant cells were sensitive to 2-DG plus BSO/AUR. In
response to 2-DG/BSO/AUR treatment, we observed increased levels of intracellular
oxidized glutathione, redox-sensitive dye oxidation, and decreased glucose
utilization via multiple metabolic pathways including the tricarboxylic acid
cycle. 2-DG/BSO/AUR treatment delayed the growth of tumors composed of
intermediate radioresistant cells and effectively radiosensitized these tumors at
clinically relevant radiation doses both in vitro and in vivo Overall, our
results support inhibition of glycolysis and intracellular redox metabolism as an
effective alternative drug strategy for the treatment of highly glycolytic and
radioresistant cervical cancers.Significance: This study suggests a simple
metabolic approach to strike at an apparent Achilles' heel in highly glycolytic,
radioresistant forms of cervical cancers, possibly with broader applications in
cancer therapy. Cancer Res; 78(6); 1392-403. (c)2018 AACR.
PMID- 29339541
TI - PHD3 Controls Lung Cancer Metastasis and Resistance to EGFR Inhibitors through
TGFalpha.
AB - Lung cancer is the leading cause of cancer-related death worldwide, in large part
due to its high propensity to metastasize and to develop therapy resistance.
Adaptive responses to hypoxia and epithelial-mesenchymal transition (EMT) are
linked to tumor metastasis and drug resistance, but little is known about how
oxygen sensing and EMT intersect to control these hallmarks of cancer. Here, we
show that the oxygen sensor PHD3 links hypoxic signaling and EMT regulation in
the lung tumor microenvironment. PHD3 was repressed by signals that induce EMT
and acted as a negative regulator of EMT, metastasis, and therapeutic resistance.
PHD3 depletion in tumors, which can be caused by the EMT inducer TGFbeta or by
promoter methylation, enhanced EMT and spontaneous metastasis via HIF-dependent
upregulation of the EGFR ligand TGFalpha. In turn, TGFalpha stimulated EGFR,
which potentiated SMAD signaling, reinforcing EMT and metastasis. In clinical
specimens of lung cancer, reduced PHD3 expression was linked to poor prognosis
and to therapeutic resistance against EGFR inhibitors such as erlotinib.
Reexpression of PHD3 in lung cancer cells suppressed EMT and metastasis and
restored sensitivity to erlotinib. Taken together, our results establish a key
function for PHD3 in metastasis and drug resistance and suggest opportunities to
improve patient treatment by interfering with the feedforward signaling
mechanisms activated by PHD3 silencing.Significance: This study links the oxygen
sensor PHD3 to metastasis and drug resistance in cancer, with implications for
therapeutic improvement by targeting this system. Cancer Res; 78(7); 1805-19.
(c)2018 AACR.
PMID- 29339542
TI - AMPK-Akt Double-Negative Feedback Loop in Breast Cancer Cells Regulates Their
Adaptation to Matrix Deprivation.
AB - Cell detachment from the extracellular matrix triggers anoikis. Disseminated
tumor cells must adapt to survive matrix deprivation, while still retaining the
ability to attach at secondary sites and reinitiate cell division. In this study,
we elucidate mechanisms that enable reversible matrix attachment by breast cancer
cells. Matrix deprival triggered AMPK activity and concomitantly inhibited AKT
activity by upregulating the Akt phosphatase PHLPP2. The resultant
pAMPKhigh/pAktlow state was critical for cell survival in suspension, as PHLPP2
silencing also increased anoikis while impairing autophagy and metastasis. In
contrast, matrix reattachment led to Akt-mediated AMPK inactivation via PP2C
alpha-mediated restoration of the pAkthigh/pAMPKlow state. Clinical specimens of
primary and metastatic breast cancer displayed an Akt-associated gene expression
signature, whereas circulating breast tumor cells displayed an elevated AMPK
dependent gene expression signature. Our work establishes a double-negative
feedback loop between Akt and AMPK to control the switch between matrix-attached
and matrix-detached states needed to coordinate cell growth and survival during
metastasis.Significance: These findings reveal a molecular switch that regulates
cancer cell survival during metastatic dissemination, with the potential to
identify targets to prevent metastasis in breast cancer. Cancer Res; 78(6); 1497
510. (c)2018 AACR.
PMID- 29339543
TI - Genes Predisposed to DNA Hypermethylation during Acquired Resistance to
Chemotherapy Are Identified in Ovarian Tumors by Bivalent Chromatin Domains at
Initial Diagnosis.
AB - Bivalent chromatin domains containing both active H3K4me3 and repressive H3K27me3
histone marks define gene sets poised for expression or silencing in
differentiating embryonic stem (ES) cells. In cancer cells, aberrantly poised
genes may facilitate changes in transcriptional states after exposure to
anticancer drugs. In this study, we used ChIP-seq to characterize genome-wide
positioning of H3K4me3- and H3K27me3-associated chromatin in primary high-grade
serous ovarian carcinomas and in normal ovarian surface and fallopian tube
tissue. Gene sets with proximal bivalent marks defined in this manner were
evaluated subsequently as signatures of systematic change in DNA methylation and
gene expression, comparing pairs of tissue samples taken from patients at primary
presentation and relapse following chemotherapy. We found that gene sets
harboring bivalent chromatin domains at their promoters in tumor tissue, but not
normal epithelia, overlapped with Polycomb-repressive complex target genes as
well as transcriptionally silenced genes in normal ovarian and tubal stem cells.
The bivalently marked genes we identified in tumors before chemotherapy displayed
increased promoter CpG methylation and reduced gene expression at relapse after
chemotherapy of ovarian cancer. Overall, our results support the hypothesis that
preexisting histone modifications at genes in a poised chromatin state may lead
to epigenetic silencing during acquired drug resistance.Significance: These
results suggest epigenetic targets for intervention to prevent the emergence of
cancer drug resistance. Cancer Res; 78(6); 1383-91. (c)2018 AACR.
PMID- 29339544
TI - Role of Chromatin Damage and Chromatin Trapping of FACT in Mediating the
Anticancer Cytotoxicity of DNA-Binding Small-Molecule Drugs.
AB - Precisely how DNA-targeting chemotherapeutic drugs trigger cancer cell death
remains unclear, as it is difficult to separate direct DNA damage from other
effects in cells. Recent work on curaxins, a class of small-molecule drugs with
broad anticancer activity, shows that they interfere with histone-DNA
interactions and destabilize nucleosomes without causing detectable DNA damage.
Chromatin damage caused by curaxins is sensed by the histone chaperone FACT,
which binds unfolded nucleosomes becoming trapped in chromatin. In this study, we
investigated whether classical DNA-targeting chemotherapeutic drugs also
similarly disturbed chromatin to cause chromatin trapping of FACT (c-trapping).
Drugs that directly bound DNA induced both chromatin damage and c-trapping.
However, chromatin damage occurred irrespective of direct DNA damage and was
dependent on how a drug bound DNA, specifically, in the way it bound
chromatinized DNA in cells. FACT was sensitive to a plethora of nucleosome
perturbations induced by DNA-binding small molecules, including displacement of
the linker histone, eviction of core histones, and accumulation of negative
supercoiling. Strikingly, we found that the cytotoxicity of DNA-binding small
molecules correlated with their ability to cause chromatin damage, not DNA
damage. Our results suggest implications for the development of chromatin
damaging agents as selective anticancer drugs.Significance: These provocative
results suggest that the anticancer efficacy of traditional DNA-targeting
chemotherapeutic drugs may be based in large part on chromatin damage rather than
direct DNA damage. Cancer Res; 78(6); 1431-43. (c)2018 AACR.
PMID- 29339545
TI - Perioperative Implementation of Noninvasive Positive Airway Pressure Therapies.
AB - Noninvasively applied positive airway pressure therapy (PAP) is available in 3
basic modes: continuous positive airway pressure (CPAP), bi-level positive airway
pressure (BPAP), and adaptive servo-ventilation. These are in widespread use in
home and hospital settings to treat a variety of disorders of ventilation or gas
exchange, including obstructive sleep apnea, sleep-related hypoventilation,
periodic breathing, acute and chronic hypercapnic respiratory failure, and acute
respiratory failure. They are increasingly being used perioperatively to prevent
or treat upper airway obstruction, hypoventilation, and periodic breathing, and
they have been found to improve postoperative outcomes in the case of obstructive
sleep apnea. An impediment to their use in this setting is a lack of familiarity
with their application by hospital clinical staff. This review describes the
modes of PAP therapy available, their indications, how therapy is initiated, how
efficacy is assessed, common problems encountered with its use, and how these
problems can be addressed.
PMID- 29339546
TI - Correction: Interventions that improve maternity care for immigrant women in the
UK: protocol for a narrative synthesis systematic review.
PMID- 29339547
TI - Opinion: Measuring how countries adapt to societal aging.
PMID- 29339549
TI - APOL1 Genotype and Renal Function of Black Living Donors.
AB - Black living kidney donors are at higher risk of developing kidney disease than
white donors. We examined the effect of the APOL1 high-risk genotype on
postdonation renal function in black living kidney donors and evaluated whether
this genotype alters the association between donation and donor outcome. We
grouped 136 black living kidney donors as APOL1 high-risk (two risk alleles;
n=19; 14%) or low-risk (one or zero risk alleles; n=117; 86%) genotype.
Predonation characteristics were similar between groups, except for lower mean+/
SD baseline eGFR (CKD-EPI equation) in donors with the APOL1 high-risk genotype
(98+/-17 versus 108+/-20 ml/min per 1.73 m2; P=0.04). At a median of 12 years
after donation, donors with the APOL1 high-risk genotype had lower eGFR (57+/-18
versus 67+/-15 ml/min per 1.73 m2; P=0.02) and faster decline in eGFR after
adjusting for predonation eGFR (1.19; 95% confidence interval, 0 to 2.3 versus
0.4; 95% confidence interval, 0.1 to 0.7 ml/min per 1.73 m2 per year, P=0.02).
Two donors developed ESRD; both carried the APOL1 high-risk genotype. In a
subgroup of 115 donors matched to 115 nondonors by APOL1 genotype, we did not
find a difference between groups in the rate of eGFR decline (P=0.39) or any
statistical interaction by APOL1 status (P=0.92). In conclusion, APOL1 high-risk
genotype in black living kidney donors associated with greater decline in
postdonation kidney function. Trajectory of renal function was similar between
donors and nondonors. The association between APOL1 high-risk genotype and poor
renal outcomes in kidney donors requires validation in a larger study.
PMID- 29339550
TI - Relative Target Affinities of T-Cell-Dependent Bispecific Antibodies Determine
Biodistribution in a Solid Tumor Mouse Model.
AB - Anti-HER2/CD3, a T-cell-dependent bispecific antibody (TDB) construct, induces T
cell-mediated cell death in cancer cells expressing HER2 by cross-linking tumor
HER2 with CD3 on cytotoxic T cells, thereby creating a functional cytolytic
synapse. TDB design is a very challenging process that requires consideration of
multiple parameters. Although therapeutic antibody design strategy is commonly
driven by striving for the highest attainable antigen-binding affinity, little is
known about how the affinity of each TDB arm can affect the targeting ability of
the other arm and the consequent distribution and efficacy. To our knowledge, no
distribution studies have been published using preclinical models wherein the T
cell-targeting arm of the TDB is actively bound to T cells. We used a combined
approach involving radiochemistry, invasive biodistribution, and noninvasive
single-photon emission tomographic (SPECT) imaging to measure TDB distribution
and catabolism in transgenic mice with human CD3epsilon expression on T cells.
Using CD3 affinity variants, we assessed the impact of CD3 affinity on short-term
pharmacokinetics, tissue distribution, and cellular uptake. Our experimental
approach determined the relative effects of (i) CD3 targeting to normal tissues,
(ii) HER2 targeting to HER2-expressing tumors, and (iii) relative HER2/CD3
affinity, all as critical drivers for TDB distribution. We observed a strong
correlation between CD3 affinity and distribution to T-cell-rich tissues, with
higher CD3 affinity reducing systemic exposure and shifting TDB distribution away
from tumor to T-cell-containing tissues. These observations have important
implications for clinical translation of bispecific antibodies for cancer
immunotherapy. Mol Cancer Ther; 17(4); 776-85. (c)2018 AACR.
PMID- 29339551
TI - Inhibition of FLT3 and PIM Kinases by EC-70124 Exerts Potent Activity in
Preclinical Models of Acute Myeloid Leukemia.
AB - Internal tandem duplication (ITD) or tyrosine kinase domain mutations of FLT3 is
the most frequent genetic alteration in acute myelogenous leukemia (AML) and are
associated with poor disease outcome. Despite considerable efforts to develop
single-target FLT3 drugs, so far, the most promising clinical response has been
achieved using the multikinase inhibitor midostaurin. Here, we explore the
activity of the indolocarbazole EC-70124, from the same chemical space as
midostaurin, in preclinical models of AML, focusing on those bearing FLT3-ITD
mutations. EC-70124 potently inhibits wild-type and mutant FLT3, and also other
important kinases such as PIM kinases. EC-70124 inhibits proliferation of AML
cell lines, inducing cell-cycle arrest and apoptosis. EC-70124 is orally
bioavailable and displays higher metabolic stability and lower human protein
plasma binding compared with midostaurin. Both in vitro and in vivo
pharmacodynamic analyses demonstrate inhibition of FLT3-STAT5, Akt-mTOR-S6, and
PIM-BAD pathways. Oral administration of EC-70124 in FLT3-ITD xenograft models
demonstrates high efficacy, reaching complete tumor regression. Ex vivo, EC-70124
impaired cell viability in leukemic blasts, especially from FLT3-ITD patients.
Our results demonstrate the ability of EC-70124 to reduce proliferation and
induce cell death in AML cell lines, patient-derived leukemic blast and xenograft
animal models, reaching best results in FLT3 mutants that carry other molecular
pathways' alterations. Thus, its unique inhibition profile warrants EC-70124 as a
promising agent for AML treatment based on its ability to interfere the complex
oncogenic events activated in AML at several levels. Mol Cancer Ther; 17(3); 614
24. (c)2018 AACR.
PMID- 29339552
TI - Mechanisms of redox metabolism and cancer cell survival during extracellular
matrix detachment.
AB - Nontransformed cells that become detached from the extracellular matrix (ECM)
undergo dysregulation of redox homeostasis and cell death. In contrast, cancer
cells often acquire the ability to mitigate programmed cell death pathways and
recalibrate the redox balance to survive after ECM detachment, facilitating
metastatic dissemination. Accordingly, recent studies of the mechanisms by which
cancer cells overcome ECM detachment-induced metabolic alterations have focused
on mechanisms in redox homeostasis. The insights into these mechanisms may inform
the development of therapeutics that manipulate redox homeostasis to eliminate
ECM-detached cancer cells. Here, we review how ECM-detached cancer cells balance
redox metabolism for survival.
PMID- 29339553
TI - Engineering abiotic stress response in plants for biomass production.
AB - One of the major challenges in today's agriculture is to achieve enhanced plant
growth and biomass even under adverse environmental conditions. Recent
advancements in genetics and molecular biology have enabled the identification of
a complex signaling network contributing toward plant growth and development on
the one hand and abiotic stress response on the other hand. As an outcome of
these studies, three major approaches have been identified as having the
potential to improve biomass production in plants under abiotic stress
conditions. These approaches deal with having changes in the following: (i) plant
microbe interactions; (ii) cell wall biosynthesis; and (iii) phytohormone levels.
At the same time, employing functional genomics and genetics-based approaches, a
very large number of genes have been identified that play a key role in abiotic
stress tolerance. Our Minireview is an attempt to unveil the cross-talk that has
just started to emerge between the transcriptional circuitries for biomass
production and abiotic stress response. This knowledge may serve as a valuable
resource to eventually custom design the crop plants for higher biomass
production, in a more sustainable manner, in marginal lands under variable
climatic conditions.
PMID- 29339554
TI - Synthetic biology strategies for improving microbial synthesis of "green"
biopolymers.
AB - Polysaccharide-based biopolymers have many material properties relevant to
industrial and medical uses, including as drug delivery agents, wound-healing
adhesives, and food additives and stabilizers. Traditionally, polysaccharides are
obtained from natural sources. Microbial synthesis offers an attractive
alternative for sustainable production of tailored biopolymers. Here, we review
synthetic biology strategies for select "green" biopolymers: cellulose, alginate,
chitin, chitosan, and hyaluronan. Microbial production pathways, opportunities
for pathway yield improvements, and advances in microbial engineering of
biopolymers in various hosts are discussed. Taken together, microbial engineering
has expanded the repertoire of green biological chemistry by increasing the
diversity of biobased materials.
PMID- 29339555
TI - The redox requirements of proliferating mammalian cells.
AB - Cell growth and division require nutrients, and proliferating cells use a variety
of sources to acquire the amino acids, lipids, and nucleotides that support
macromolecule synthesis. Lipids are more reduced than other nutrients, whereas
nucleotides and amino acids are typically more oxidized. Cells must therefore
generate reducing and oxidizing (redox) equivalents to convert consumed nutrients
into biosynthetic precursors. To that end, redox cofactor metabolism plays a
central role in meeting cellular redox requirements. In this Minireview, we
highlight the biosynthetic pathways that involve redox reactions and discuss
their integration with metabolism in proliferating mammalian cells.
PMID- 29339556
TI - Evidence of a sequestered imine intermediate during reduction of nitrile to amine
by the nitrile reductase QueF from Escherichia coli.
AB - In the biosynthesis of the tRNA-inserted nucleoside queuosine, the nitrile
reductase QueF catalyzes conversion of 7-cyano-7-deazaguanine (preQ0) to 7
aminomethyl-7-deazaguanine (preQ1), a biologically unique four-electron reduction
of a nitrile to an amine. The QueF mechanism involves a covalent thioimide adduct
between the enzyme and preQ0 that undergoes reduction to preQ1 in two NADPH
dependent steps, presumably via an imine intermediate. Protecting a labile imine
from interception by water is fundamental to QueF catalysis for proper enzyme
function. In the QueF from Escherichia coli, the conserved Glu89 and Phe228
residues together with a mobile structural element composing the catalytic Cys190
form a substrate-binding pocket that secludes the bound preQ0 completely from
solvent. We show here that residue substitutions (E89A, E89L, and F228A) targeted
at opening up the binding pocket weakened preQ0 binding at the preadduct stage by
up to +10 kJ/mol and profoundly affected catalysis. Unlike wildtype enzyme, the
QueF variants, including L191A and I192A, were no longer selective for preQ1
formation. The E89A, E89L, and F228A variants performed primarily (>=90%) a two
electron reduction of preQ0, releasing hydrolyzed imine (7-formyl-7-deazaguanine)
as the product. The preQ0 reduction by L191A and I192A gave preQ1 and 7-formyl-7
deazaguanine at a 4:1 and 1:1 ratio, respectively. The proportion of 7-formyl-7
deazaguanine in total product increased with increasing substrate concentration,
suggesting a role for preQ0 in a competitor-induced release of the imine
intermediate. Collectively, these results provide direct evidence for the
intermediacy of an imine in the QueF-catalyzed reaction. They reveal determinants
of QueF structure required for imine sequestration and hence for a complete
nitrile-to-amine conversion by this class of enzymes.
PMID- 29339557
TI - Chronic dietary creatine enhances hippocampal-dependent spatial memory,
bioenergetics, and levels of plasticity-related proteins associated with NF
kappaB.
AB - The brain has a high demand for energy, of which creatine (Cr) is an important
regulator. Studies document neurocognitive benefits of oral Cr in mammals, yet
little is known regarding their physiological basis. This study investigated the
effects of Cr supplementation (3%, w/w) on hippocampal function in male C57BL/6
mice, including spatial learning and memory in the Morris water maze and oxygen
consumption rates from isolated mitochondria in real time. Levels of
transcription factors and related proteins (CREB, Egr1, and IkappaB to indicate
NF-kappaB activity), proteins implicated in cognition (CaMKII, PSD-95, and Egr2),
and mitochondrial proteins (electron transport chain Complex I, mitochondrial
fission protein Drp1) were probed with Western blotting. Dietary Cr decreased
escape latency/time to locate the platform (P < 0.05) and increased the time
spent in the target quadrant (P < 0.01) in the Morris water maze. This was
accompanied by increased coupled respiration (P < 0.05) in isolated hippocampal
mitochondria. Protein levels of CaMKII, PSD-95, and Complex 1 were increased in
Cr-fed mice, whereas IkappaB was decreased. These data demonstrate that dietary
supplementation with Cr can improve learning, memory, and mitochondrial function
and have important implications for the treatment of diseases affecting memory
and energy homeostasis.
PMID- 29339558
TI - Does sleep facilitate the consolidation of allocentric or egocentric
representations of implicitly learned visual-motor sequence learning?
AB - Sleep facilitates the consolidation (i.e., enhancement) of simple, explicit
(i.e., conscious) motor sequence learning (MSL). MSL can be dissociated into
egocentric (i.e., motor) or allocentric (i.e., spatial) frames of reference. The
consolidation of the allocentric memory representation is sleep-dependent,
whereas the egocentric consolidation process is independent of sleep or wake for
explicit MSL. However, it remains unclear the extent to which sleep contributes
to the consolidation of implicit (i.e., unconscious) MSL, nor is it known what
aspects of the memory representation (egocentric, allocentric) are consolidated
by sleep. Here, we investigated the extent to which sleep is involved in
consolidating implicit MSL, specifically, whether the egocentric or the
allocentric cognitive representations of a learned sequence are enhanced by
sleep, and whether these changes support the development of explicit sequence
knowledge across sleep but not wake. Our results indicate that egocentric and
allocentric representations can be behaviorally dissociated for implicit MSL.
Neither representation was preferentially enhanced across sleep nor were
developments of explicit awareness observed. However, after a 1-wk interval
performance enhancement was observed in the egocentric representation. Taken
together, these results suggest that like explicit MSL, implicit MSL has
dissociable allocentric and egocentric representations, but unlike explicit
sequence learning, implicit egocentric and allocentric memory consolidation is
independent of sleep, and the time-course of consolidation differs significantly.
PMID- 29339559
TI - Evidence of structure and persistence in motivational attraction to serial
Pavlovian cues.
AB - Sign-tracking is a form of autoshaping where animals develop conditioned
responding directed toward stimuli predictive of an outcome even though the
outcome is not contingent on the animal's behavior. Sign-tracking behaviors are
thought to arise out of the attribution of incentive salience (i.e., motivational
value) to reward-predictive cues. It is not known how incentive salience would be
attributed to serially occurring cues, despite cues often occurring in a sequence
in the real world as reward approaches. The experiments presented here
demonstrate that reward-proximal cue responding is not altered by the presence of
a distal reward cue (Experiment 1), and similarly that reward-distal cue
responding which animals favor, is not altered by the presence of a reward
proximal cue (Experiment 2). Extinction of reward-proximal cues after training of
the serial sequence leads to a generalized reduction in lever responding
(Experiment 3). Together, we show that both Pavlovian serial lever cues acquire
motivational value. These experiments also provide support to the notion that
sign-tracking responses are insensitive to changes in outcome value, and that
responding to serial cues creates a distinct context for outcome value.
PMID- 29339560
TI - Molecular correlates of separate components of training that contribute to long
term memory formation after learning that food is inedible in Aplysia.
AB - Training Aplysia with inedible food for a period that is too brief to produce
long-term memory becomes effective in producing memory when training is paired
with a nitric oxide (NO) donor. Lip stimulation for the same period of time
paired with an NO donor is ineffective. Using qPCR, we examined molecular
correlates of brief training versus lip stimulation, of treatment with an NO
donor versus saline, and of the combined stimuli producing long-term memory.
Changes were examined in mRNA expression of Aplysia homologs of C/EBP, CREB1,
CREB1alpha, CREB1beta, and CREB2, in both the buccal and cerebral ganglia
controlling feeding. Both the brief training and the NO donor increased
expression of C/EBP, CREB1, CREB1alpha, and CREB1beta, but not CREB2 in the
buccal ganglia. For CREB1alpha, there was a significant interaction between the
effects of the brief training and of the NO donor. In addition, the NO donor, but
not brief training, increased expression of all of the genes in the cerebral
ganglion. These findings show that the components of learning that alone do not
produce memory produce molecular changes in different ganglia. Thus, long-term
memory is likely to arise by both additive and interactive increases in gene
expression.
PMID- 29339561
TI - Prepared stimuli enhance aversive learning without weakening the impact of verbal
instructions.
AB - Fear-relevant stimuli such as snakes and spiders are thought to capture attention
due to evolutionary significance. Classical conditioning experiments indicate
that these stimuli accelerate learning, while instructed extinction experiments
suggest they may be less responsive to instructions. We manipulated stimulus type
during instructed aversive reversal learning and used quantitative modeling to
simultaneously test both hypotheses. Skin conductance reversed immediately upon
instruction in both groups. However, fear-relevant stimuli enhanced dynamic
learning, as measured by higher learning rates in participants conditioned with
images of snakes and spiders. Results are consistent with findings that
dissociable neural pathways underlie feedback-driven and instructed aversive
learning.
PMID- 29339562
TI - Sleep-dependent reductions in reality-monitoring errors arise from more
conservative decision criteria.
AB - Reality-monitoring errors occur when internally generated thoughts are remembered
as external occurrences. We hypothesized that sleep-dependent memory
consolidation could reduce them by strengthening connections between items and
their contexts during an afternoon nap. Participants viewed words and imagined
their referents. Pictures of the referents also accompanied half of the words.
After a 2-h break filled with sleep (n = 31) or wakefulness (n = 32),
participants indicated if they previously viewed a picture of each word. Nap
participants made fewer reality-monitoring errors than wake participants by
adopting more stringent response criteria, suggesting that sleep reduces reality
monitoring errors primarily by influencing post-retrieval decision processes.
PMID- 29339563
TI - The Diagnosis of UTI: Colony Count Criteria Revisited.
PMID- 29339564
TI - Accuracy of the Urinalysis for Urinary Tract Infections in Febrile Infants 60
Days and Younger.
AB - OBJECTIVES: Reports of the test accuracy of the urinalysis for diagnosing urinary
tract infections (UTIs) in young febrile infants have been variable. We evaluated
the test characteristics of the urinalysis for diagnosing UTIs, with and without
associated bacteremia, in young febrile infants. METHODS: We performed a planned
secondary analysis of data from a prospective study of febrile infants <=60 days
old at 26 emergency departments in the Pediatric Emergency Care Applied Research
Network. We evaluated the test characteristics of the urinalysis for diagnosing
UTIs, with and without associated bacteremia, by using 2 definitions of UTI:
growth of >=50 000 or >=10 000 colony-forming units (CFUs) per mL of a
uropathogen. We defined a positive urinalysis by the presence of any leukocyte
esterase, nitrite, or pyuria (>5 white blood cells per high-power field).
RESULTS: Of 4147 infants analyzed, 289 (7.0%) had UTIs with colony counts >=50
000 CFUs/mL, including 27 (9.3%) with bacteremia. For these UTIs, a positive
urinalysis exhibited sensitivities of 0.94 (95% confidence interval [CI]: 0.91
0.97), regardless of bacteremia; 1.00 (95% CI: 0.87-1.00) with bacteremia; and
0.94 (95% CI: 0.90-0.96) without bacteremia. Specificity was 0.91 (95% CI: 0.90
0.91) in all groups. For UTIs with colony counts >=10 000 CFUs/mL, the
sensitivity of the urinalysis was 0.87 (95% CI: 0.83-0.90), and specificity was
0.91 (95% CI: 0.90-0.92). CONCLUSIONS: The urinalysis is highly sensitive and
specific for diagnosing UTIs, especially with >=50 000 CFUs/mL, in febrile
infants <=60 days old, and particularly for UTIs with associated bacteremia.
PMID- 29339566
TI - Graphene Dirac point tuned by ferroelectric polarization field.
AB - Graphene has received numerous attention for future nanoelectronics and
optoelectronics. The Dirac point is a key parameter of graphene that provides
information about its carrier properties. There are lots of methods to tune the
Dirac point of graphene, such as chemical doping, impurities, defects, and
disorder. In this study, we report a different approach to tune the Dirac point
of graphene using a ferroelectric polarization field. The Dirac point can be
adjusted to near the ferroelectric coercive voltage regardless its original
position. We have ensured this phenomenon by temperature-dependent experiments,
and analyzed its mechanism with the theory of impurity correlation in graphene.
Additionally, with the modulation of ferroelectric polymer, the current on/off
ratio and mobility of graphene transistor both have been improved. This work
provides an effective method to tune the Dirac point of graphene, which can be
readily used to configure functional devices such as p-n junctions and inverters.
PMID- 29339565
TI - A Home Visiting Parenting Program and Child Obesity: A Randomized Trial.
AB - BACKGROUND: Young children living in historically marginalized families are at
risk for becoming adolescents with obesity and subsequently adults with increased
obesity-related morbidities. These risks are particularly acute for Hispanic
children. We hypothesized that the prevention-focused, socioecological approach
of the "Minding the Baby" (MTB) home visiting program might decrease the rate of
childhood overweight and obesity early in life. METHODS: This study is a
prospective longitudinal cohort study in which we include data collected during 2
phases of the MTB randomized controlled trial. First-time, young mothers who
lived in medically underserved communities were invited to participate in the MTB
program. Data were collected on demographics, maternal mental health, and
anthropometrics of 158 children from birth to 2 years. RESULTS: More children in
the intervention group had a healthy BMI at 2 years. The rate of obesity was
significantly higher (P < .01) in the control group (19.7%) compared with the
intervention group (3.3%) at this age. Among Hispanic families, children in the
MTB intervention were less likely to have overweight or obesity (odds ratio =
0.32; 95% confidence interval: 0.13-0.78). CONCLUSIONS: Using the MTB program, we
significantly lowered the rate of obesity among 2-year-old children living in low
socioeconomic-status communities. In addition, children of Hispanic mothers were
less likely to have overweight or obesity at 2 years. Given the high and
disproportionate national prevalence of Hispanic young children with overweight
and obesity and the increased costs of obesity-related morbidities, these
findings have important clinical, research, and policy implications.
PMID- 29339567
TI - Erythrocyte membrane-coated gold nanocages for targeted photothermal and chemical
cancer therapy.
AB - Recently, red blood cell (RBC) membrane-coated nanoparticles have attracted much
attention because of their excellent immune escapability; meanwhile, gold
nanocages (AuNs) have been extensively used for cancer therapy due to their
photothermal effect and drug delivery capability. The combination of the RBC
membrane coating and AuNs may provide an effective approach for targeted cancer
therapy. However, few reports have shown the utilization of combining these two
technologies. Here, we design erythrocyte membrane-coated gold nanocages for
targeted photothermal and chemical cancer therapy. First, anti-EpCam antibodies
were used to modify the RBC membranes to target 4T1 cancer cells. Second, the
antitumor drug paclitaxel (PTX) was encapsulated into AuNs. Then, the AuNs were
coated with the modified RBC membranes. These new nanoparticles were termed EpCam
RPAuNs. We characterized the capability of the EpCam-RPAuNs for selective tumor
targeting via exposure to near-infrared irradiation. The experimental results
demonstrate that EpCam-RPAuNs can effectively generate hyperthermia and precisely
deliver the antitumor drug PTX to targeted cells. We also validated the
biocompatibility of the EpCam-RAuNs in vitro. By combining the molecularly
modified targeting RBC membrane and AuNs, our approach provides a new way to
design biomimetic nanoparticles to enhance the surface functionality of
nanoparticles. We believe that EpCam-RPAuNs can be potentially applied for cancer
diagnoses and therapies.
PMID- 29339568
TI - Bone surface enhancement in ultrasound images using a new Doppler-based
acquisition/processing method.
AB - Ultrasound (US) imaging has long been considered as a potential aid in orthopedic
surgeries. US technologies are safe, portable and do not use radiations. This
would make them a desirable tool for real-time assessment of fractures and to
monitor fracture healing. However, image quality of US imaging methods in bone
applications is limited by speckle, attenuation, shadow, multiple reflections and
other imaging artifacts. While bone surfaces typically appear in US images as
somewhat 'brighter' than soft tissue, they are often not easily distinguishable
from the surrounding tissue. Therefore, US imaging methods aimed at segmenting
bone surfaces need enhancement in image contrast prior to segmentation to improve
the quality of the detected bone surface. In this paper, we present a novel
acquisition/processing technique for bone surface enhancement in US images.
Inspired by elastography and Doppler imaging methods, this technique takes
advantage of the difference between the mechanical and acoustic properties of
bones and those of soft tissues to make the bone surface more easily
distinguishable in US images. The objective of this technique is to facilitate US
based bone segmentation methods and improve the accuracy of their outcomes. The
newly proposed technique is tested both in in vitro and in vivo experiments. The
results of these preliminary experiments suggest that the use of the proposed
technique has the potential to significantly enhance the detectability of bone
surfaces in noisy ultrasound images.
PMID- 29339569
TI - Experimental determination of configurational entropy in a two-dimensional liquid
under random pinning.
AB - A quasi two-dimensional colloidal suspension is studied under the influence of
immobilisation (pinning) of a random fraction of its particles. We introduce a
novel experimental method to perform random pinning and, with the support of
numerical simulation, we find that increasing the pinning concentration smoothly
arrests the system, with a cross-over from a regime of high mobility and high
entropy to a regime of low mobility and low entropy. At the local level, we study
fluctuations in area fraction and concentration of pins and map them to entropic
structural signatures and local mobility, obtaining a measure for the local
entropic fluctuations of the experimental system.
PMID- 29339570
TI - Comparison of Monte Carlo and analytical dose computations for intensity
modulated proton therapy.
AB - To evaluate the effect of approximations in clinical analytical calculations
performed by a treatment planning system (TPS) on dosimetric indices in intensity
modulated proton therapy. TPS calculated dose distributions were compared with
dose distributions as estimated by Monte Carlo (MC) simulations, calculated with
the fast dose calculator (FDC) a system previously benchmarked to full MC. This
study analyzed a total of 525 patients for four treatment sites (brain, head-and
neck, thorax and prostate). Dosimetric indices (D02, D05, D20, D50, D95, D98, EUD
and Mean Dose) and a gamma-index analysis were utilized to evaluate the
differences. The gamma-index passing rates for a 3%/3 mm criterion for voxels
with a dose larger than 10% of the maximum dose had a median larger than 98% for
all sites. The median difference for all dosimetric indices for target volumes
was less than 2% for all cases. However, differences for target volumes as large
as 10% were found for 2% of the thoracic patients. For organs at risk (OARs), the
median absolute dose difference was smaller than 2 Gy for all indices and
cohorts. However, absolute dose differences as large as 10 Gy were found for some
small volume organs in brain and head-and-neck patients. This analysis concludes
that for a fraction of the patients studied, TPS may overestimate the dose in the
target by as much as 10%, while for some OARs the dose could be underestimated by
as much as 10 Gy. Monte Carlo dose calculations may be needed to ensure more
accurate dose computations to improve target coverage and sparing of OARs in
proton therapy.
PMID- 29339571
TI - Infrared photoconductivity and photovoltaic response from nanoscale domains of
PbS alloyed with thorium and oxygen.
AB - Thin films of lead sulfide alloyed with thorium and oxygen were deposited on GaAs
substrates and processed to produce a photo-diode structure. Structural, optical
and electrical characterizations indicate the presence of small nanoscale domains
(NDs) that are characterized by dense packaging, high quality interfaces and a
blue-shift of the energy bandgap toward the short wavelength infrared range of
the spectrum. Photocurrent spectroscopy revealed a considerable photoconductivity
that is correlated with excitation of carriers in the NDs of lead sulfide alloyed
with thorium and oxygen. Furthermore, the appearance of a photovoltaic effect
under near infrared illumination indicates a quasi-type II band alignment at the
interface of the GaAs and the film of NDs.
PMID- 29339572
TI - Three-dimensional cross-linking composite of graphene, carbon nanotube and Si
nanoparticles for lithium ion batteries anode.
AB - Various graphene-based Si nanocomposites have been reported to improve the
performance of active materials in
Li ion battery. However, these
candidates still yield severe capacity fading due to the electrical disconnection
and
fracture caused by huge volume changes with extended cycles.Therefore,
we design a novel three-dimensional
cross-linking structure of graphene and
single-wall carbon nanotube to encapsulate Si nanoparticles. The
synthesized three-dimensional structure is ascribed to the excellent self
assembly of carbon nanotube with
graphene oxide and a thermal treatment
process at 900 oC. This special structure provides sufficient void spaces
for volume expansion of Si nanoparticles and channels for the diffusion of ions
and electrons, and the
cross-linking of graphene and single wall carbon
nanotube also strengthens the stability of structure. As a result,
the
volume expansion of Si nanoparticles is restrained. The specific capacity remains
1450 mAh g-1 after 100
cycles at 200 mA g-1. This well-defined three
dimensional structure facilitates superior capacity and cycling
stability
in comparison with bare Si and mechanically mixed composite electrode of
graphene, single-wall
carbon nanotube and silicon nanoparticles.
PMID- 29339573
TI - 18F-choline PET/CT for parathyroid scintigraphy: significantly lower radiation
exposure of patients in comparison to conventional nuclear medicine imaging
approaches.
AB - BACKGROUND: Parathyroid subtraction scintigraphy (PSS) is the most commonly used
imaging method for localisation of hyperfunctioning parathyroid glands (HPGs) in
primary hyperparathyroidism (PHP), a common endocrine disorder. Hybrid (SPECT/CT)
imaging with 99mTc-sestaMIBI (MIBI) at an early and delayed phase (dual-phase
imaging) may be the most accurate conventional imaging approach, but includes
additional radiation exposure due to added CT imaging. Recently, 18F-choline
(FCH) PET/CT was introduced for HPG imaging, which can also be performed using
the dual-phase approach. To date, no studies have compared organ doses and the
effective dose (ED) from conventional subtraction scintigraphy, dual-phase MIBI
SPECT/CT, and FCH PET/CT in the localisation of HPGs. AIM: In addition to the
comparison of the diagnostic performance of FCH PET/CT and conventional
scintigraphic imaging methods, the aim of the study was to measure the organ
doses and the ED for conventional subtraction parathyroid imaging protocols,
using dual-phase MIBI SPECT/CT as a potential conventional imaging method of
choice and FCH dual-phase PET/CT as a potential future imaging method of choice
for the localisation of HPGs. Materials, methods. Thirty-six patients referred
for parathyroid imaging with a clinical indication of PHP underwent preoperative
PSS and dual-phase SPECT/CT imaging with the addition of FCH PET/CT. The
diagnostic performance of the imaging modalities was assessed by using histology
results as a gold standard. Radiation exposure was calculated for the
administered activities of radiopharmaceuticals using ICRP80 weighting factors
and for CT exposure at hybrid imaging using dose-length products and the ImPACT
CT Patient Dosimetry Calculator. RESULTS: The diagnostic performance of FCH
PET/CT was significantly better than that of conventional imaging modalities
(sensitivity of 97% vs 64% and 46% for MIBI SPECT/CT and PSS, respectively, with
comparable specificity of over 95% for all modalities). The highest radiation
exposure was caused by conventional PSS (7.4 mSv), followed by dual-phase MIBI
SPECT/CT (6.8 mSv). The radiation exposure was the lowest for dual-phase FCH
PET/CT imaging (2.8 mSv). The added CT imaging for both hybrid approaches did not
cause significant additional radiation exposure (1.4 mSv for MIBI SPECT/CT,
additional 26.4% to overall exposure; 0.8 mSv for FCH PET/CT, additional 42.4% to
overall exposure). CONCLUSION: In comparison to conventional scintigraphic
imaging of HPGs, emerging hybrid (SPECT/CT, PET/CT) imaging techniques combine
superior diagnostic performance with lower radiation exposure to patients.
PMID- 29339574
TI - Phase diagram of carbon and the factors limiting the quantity and size of natural
diamonds.
AB - Phase diagrams of carbon, and those focusing on the graphite-to-diamond
transitional conditions in particular, are of great interest for fundamental and
applied research. The present study introduces a number of experiments carried
out to convert graphite under high-pressure conditions, showing a formation of
stable phase of fullerene-type onions cross-linked by sp3-bonds in the 55-115 GPa
pressure range instead of diamonds formation (even at temperature 2000-3000 K)
and the already formed diamonds turn into carbon onions. Our results refute the
widespread idea that diamonds can form at any pressure from 2.2 to 1000 GPa. The
phase diagram built within this study allows us not only to explain the existing
numerous experimental data on the formation of diamond from graphite, but also to
make assumptions about the conditions of its growth in Earth's crust.
PMID- 29339575
TI - Dynamic PET image reconstruction integrating temporal regularization associated
with respiratory motion correction for applications in oncology.
AB - Respiratory motion reduces both the qualitative and quantitative accuracy of PET
images in oncology. This impact is more significant for quantitative applications
based on kinetic modeling, where dynamic acquisitions are associated with limited
statistics due to the necessity of enhanced temporal resolution. The aim of this
study is to address these drawbacks, by combining a respiratory motion correction
approach with temporal regularization in a unique reconstruction algorithm for
dynamic PET imaging. Elastic transformation parameters for the motion correction
are estimated from the non-attenuation-corrected PET images. The derived
displacement matrices are subsequently used in a list-mode based OSEM
reconstruction algorithm integrating a temporal regularization between the 3D
dynamic PET frames, based on temporal basis functions. These functions are
simultaneously estimated at each iteration, along with their relative
coefficients for each image voxel. Quantitative evaluation has been performed
using dynamic FDG PET/CT acquisitions of lung cancer patients acquired on a GE
DRX system. The performance of the proposed method is compared with that of a
standard multi-frame OSEM reconstruction algorithm. The proposed method achieved
substantial improvements in terms of noise reduction while accounting for loss of
contrast due to respiratory motion. Results on simulated data showed that the
proposed 4D algorithms led to bias reduction values up to 40% in both tumor and
blood regions for similar standard deviation levels, in comparison with a
standard 3D reconstruction. Patlak parameter estimations on reconstructed images
with the proposed reconstruction methods resulted in 30% and 40% bias reduction
in the tumor and lung region respectively for the Patlak slope, and a 30% bias
reduction for the intercept in the tumor region (a similar Patlak intercept was
achieved in the lung area). Incorporation of the respiratory motion correction
using an elastic model along with a temporal regularization in the reconstruction
process of the PET dynamic series led to substantial quantitative improvements
and motion artifact reduction. Future work will include the integration of a
linear FDG kinetic model, in order to directly reconstruct parametric images.
PMID- 29339576
TI - A thermodynamics model for morphology prediction of aluminum nano crystals
fabricated by the inert gas condensation method.
AB - The purpose of this study is to provide scientific guidance for the morphological
control of nanoparticle synthesis using the gas phase method. A universal
thermodynamics model is developed to predict the morphology of nanoparticles
fabricated using the inert gas condensation method. By using this model, the
morphologies of aluminum nanocrystals are predicted under various preparation
conditions. There are two types of energy that jointly determine the formation of
nanoparticle morphology-Gibbs free energy for nanoparticles and energy variation
during the process. The results show that energy variation dominates morphology
formation when the cooling rate is less than 2 * 1011 K s-1 in the aluminum
nanocrystal production process. At the beginning of the nanoparticle growth, the
most stable morphology is predicted to be spherical, but the energetically
preferred morphology becomes cubic as the particle grows. The turning point in
the particle size at which spherical morphology is no longer the most stable
morphology is exhibited as a function of pressure in a condensation chamber for
different cooling rates. In this paper, we focus on the need for morphology
prediction based on preparation conditions. It is concluded that nanoparticles
with various morphologies could be obtained by adjusting the cooling rate and
pressure in the condensation chamber.
PMID- 29339577
TI - A wearable pressure sensor based on ultra-violet/ozone microstructured carbon
nanotube/polydimethylsiloxane arrays for electronic skins.
AB - Pressure sensors with high performance (e.g., a broad pressure sensing range,
high sensitivities, rapid response/relaxation speeds, temperature-stable
sensing), as well as a cost-effective and highly efficient fabrication method are
highly desired for electronic skins. In this research, a high-performance
pressure sensor based on microstructured carbon nanotube/polydimethylsiloxane
arrays was fabricated using an ultra-violet/ozone (UV/O3) microengineering
technique. The UV/O3 microengineering technique is controllable, cost-effective,
and highly efficient since it is conducted at room temperature in an ambient
environment. The pressure sensor offers a broad pressure sensing range (7 Pa-50
kPa), a sensitivity of ~ -0.101 +/- 0.005 kPa-1 (<1 kPa), a fast
response/relaxation speed of ~10 ms, a small dependence on temperature variation,
and a good cycling stability (>5000 cycles), which is attributed to the UV/O3
engineered microstructures that amplify and transfer external applied forces and
rapidly store/release the energy during the PDMS deformation. The sensors
developed show the capability to detect external forces and monitor human health
conditions, promising for the potential applications in electronic skin.
PMID- 29339578
TI - Functional metasurfaces based on metallic and dielectric subwavelength slits and
stripes array.
AB - Starting with the early works of extraordinary optical transmission and
extraordinary Young's interference, researchers have been fascinated by the
unusual optical properties displayed by metallic holes/slits and subsequently
found similar abnormities in dielectric counterparts. Benefiting from the
shrinking wavelength of surface plasmon polaritons excited in metallic slits and
high refractive index of dielectric stripes, one can realize local phase
modulation and approach desired dispersion by engineering the geometries of a
slits and stripes array. In this review, we review recent developments in
functional metasurfaces composed of various metallic and dielectric subwavelength
slits and stripes arrays, with special emphasis on achromatic, ultra-broadband,
quasi-continuous, multifunctional and reconfigurable metasurfaces. Particular
attention is paid to provide insight into the design strategies for these
devices. Finally, we give an outlook of the development in this fascinating area.
PMID- 29339579
TI - Conclusions and recommendations from the 17th Workshop of the European ALARA
Network 'ALARA in emergency exposure situations'.
AB - The European ALARA Network regularly organises workshops on topical issues in
radiation protection. In light of the Fukushima accident, the most recent
workshop questioned the application of the ALARA principle in emergency exposure
situations. This memorandum presents the conclusions and recommendations of this
workshop. One of the outcomes is that the process of optimisation in emergency
exposure situations should be flexible enough to be able to modify or refine
decisions over the course of an accident. In the urgent phase, decisions must be
made in a very time-constrained environment, based on scarce, uncertain and
sometimes unreliable information. In this phase, optimisation and protection
strategies are therefore developed and applied on the basis of conservative
assumptions or 'reasonably foreseeable worst-case scenario' which could lead to
an overestimation of the consequences. In the intermediate phase, knowledge of
the situation improves, and more time is available to make the decision. This is
reflected by adopting a less conservative approach, and transitioning to a more
appropriate optimisation adapted as effectively as possible to the various
exposure situations. When the situation is eventually stabilized (transition
phase), there is time to shape the measures taken previously to reflect local
conditions in the affected territories. In every phase, consideration should be
given to the stakeholders, so that their needs and requirements can be
incorporated as effectively as possible.
PMID- 29339580
TI - Advantages of soft subdural implants for the delivery of electrochemical
neuromodulation therapies to the spinal cord.
AB - OBJECTIVE: We recently developed soft neural interfaces enabling the delivery of
electrical and chemical stimulation to the spinal cord. These stimulations
restored locomotion in animal models of paralysis. Soft interfaces can be placed
either below or above the dura mater. Theoretically, the subdural location
combines many advantages, including increased selectivity of electrical
stimulation, lower stimulation thresholds, and targeted chemical stimulation
through local drug delivery. However, these advantages have not been documented,
nor have their functional impact been studied in silico or in a relevant animal
model of neurological disorders using a multimodal neural interface. APPROACH: We
characterized the recruitment properties of subdural interfaces using a realistic
computational model of the rat spinal cord that included explicit representation
of the spinal roots. We then validated and complemented computer simulations with
electrophysiological experiments in rats. We additionally performed behavioral
experiments in rats that received a lateral spinal cord hemisection and were
implanted with a soft interface. MAIN RESULTS: In silico and in vivo experiments
showed that the subdural location decreased stimulation thresholds compared to
the epidural location while retaining high specificity. This feature reduces
power consumption and risks of long-term damage in the tissues, thus increasing
the clinical safety profile of this approach. The hemisection induced a transient
paralysis of the leg ipsilateral to the injury. During this period, the delivery
of electrical stimulation restricted to the injured side combined with local
chemical modulation enabled coordinated locomotor movements of the paralyzed leg
without affecting the non-impaired leg in all tested rats. Electrode properties
remained stable over time, while anatomical examinations revealed excellent bio
integration properties. SIGNIFICANCE: Soft neural interfaces inserted subdurally
provide the opportunity to deliver electrical and chemical neuromodulation
therapies using a single, bio-compatible and mechanically compliant device that
effectively alleviates locomotor deficits after spinal cord injury.
PMID- 29339581
TI - Strain-induced bi-thermoelectricity in tapered carbon nanotubes.
AB - We show that carbon-based nanostructured materials are a novel testbed for
controlling thermoelectricity and have the potential to underpin the development
of new cost-effective environmentally-friendly thermoelectric materials. In
single-molecule junctions, it is known that transport resonances associated with
the discrete molecular levels play a key role in the thermoelectric performance,
but such resonances have not been exploited in carbon nanotubes (CNTs). Here we
study junctions formed from tapered CNTs and demonstrate that such structures
possess transport resonances near the Fermi level, whose energetic location can
be varied by applying strain, resulting in an ability to tune the sign of their
Seebeck coefficient. These results reveal that tapered CNTs form a new class of
bi-thermoelectric materials, exhibiting both positive and negative thermopower.
This ability to change the sign of the Seebeck coefficient allows the
thermovoltage in carbon-based thermoelectric devices to be boosted by placing
CNTs with alternating-sign Seebeck coefficients in tandem.
PMID- 29339582
TI - Oxidation of copper nanowire based transparent electrodes in ambient conditions
and their stabilization by encapsulation: application to transparent film
heaters.
AB - Whereas the integration of silver nanowires in functional devices has reached a
fair level of maturity, the integration of copper nanowires still remains
difficult, mainly due to the intrinsic instability of copper nanowires in ambient
conditions. In this paper, copper nanowire based transparent electrodes with good
performances (33 Omega sq-1 associated with 88% transparency) were obtained, and
their degradation in different conditions was monitored, in particular by
electrical measurements, transmission electron microscopy, x-ray photoelectron
spectrometry and Auger electron spectroscopy. Several routes to stabilize the
random networks of copper nanowires were evaluated. Encapsulation through
laminated barrier film with optical clear adhesive and atmospheric pressure
spatial atomic layer deposition were found to be efficient and were used for the
fabrication of transparent film heaters.
PMID- 29339583
TI - Echocolor Doppler morpho-functional study of the jugulo-subclavian confluence in
chronic cerebro-spinal venous insufficiency and multiple sclerosis patients.
AB - OBJECTIVES: The aim of this work is to measure the mean diameter of the
confluence jugulo- subclavian, the impact of different types of jugular
confluences and the correlation between the types of confluences and the Valsalva
maneuver (jugular reflux) in subjects with Chronic Cerebro-Spinal Venous
Insufficiency (CCSVI) and Multiple Sclerosis. METHOD: We investigated by Echo
Color-Doppler (ECD) 103 subjects (67 F 36M) of mean age 45 +/- 12 years (a
minimum of 22 to a maximum of 79 years, with a median of 44 and a modal value 42
years), mean EDSS of 4.7 and average disease duration of 12 years. RESULTS: The
103 right jugular veins investigated had an average diameter of 8.4 +/- 2.4 mm
(minimum 4.0, maximum 14.9 mm; median 7.9; modal value 7.6 mm). Three form types
were found: 56 cylindrical, 29 conical and 18 funnel. Valsalva maneuver was
positive in 30 patients. The 103 left jugular investigated had an average
diameter of 8.9 +/- 2.4 mm (minimum 2.8, maximum 14.4 mm; median of 8.8; modal
value 8.7 mm). The form types were found: 42 cylindrical, 45 conical and 16
funnel. Valsalva maneuver was positive in 30 patients. CONCLUSIONS: The mean
diameter of the jugular veins was 8.7 mm. Internal jugular veins with cylindrical
morphology have a diameter smaller than other forms; this difference is
statistically significant. The different morphology of the jugular vein
confluence does not increase the possibility of a reflux because the positive
Valsalva maneuvers are not statistically significant when compared to the various
types. KEY WORDS: CCSVI, EchoColorDoppler Map, Jugulo-Subclavian Confluence
Diameter.
PMID- 29339584
TI - Delayed diagnosis and treatment of high grade blunt pancreatic trauma. Case
report and review of literature.
AB - INTRODUCTION: Despite technological advancement, high grade pancreatic injuries
following blunt abdominal trauma continues to remain a disease that is associated
with high morbidity and mortality rates, particularly in cases of delayed
diagnosis. The aim of this paper was the presentation of delayed diagnosis and
treatment peculiarities of high grade pancreatic trauma and a review of
literature. CASE REPORT: A 55-years old man, involved in motor vehicle crashes,
was referred to our level I trauma center. Hemodynamically stable. Abdominal
physical exam, laboratory and focused abdominal sonography for trauma were
normal. First total body multidetector CT scan, performed only after 24 hours,
showed almost complete left pneumothorax, left third to fifth rib fractures and
subcutaneous emphysema. Left chest tube was applied. On the eighth post-traumatic
day, the general condition of the patient started to deteriorate. The patient
showed abdominal pain, fever, nausea, vomiting, and bilateral flank ecchymosis.
Only the third CT scan performed, on twelfth day, after the peritoneal signs,
changes in blood and biochemical parameters appear, we revealed linear laceration
and hypo-attenuation area of the neck and a part of distal body pancreas. In
laparotomy fat necrosis, giant retroperitoneal abscess, necrosis of the neck and
distal body of the pancreas, was found. Distal pancreatectomy with splenectomy
was performed. Postoperative course with extensive wound infection and necrotic
leakage from peripancreatic drain was complicated. The patient was discharged two
months after his operation without any events. CONCLUSION: On time diagnosis of
pancreatic trauma, especially in polytrauma patients, continues to remain a
challenge for trauma surgeons. Main pancreatic duct injury is an important
prognostic factor and the major one determining therapeutic approaches. Adequate
surgical approaches decrease morbidity and mortality in pancreatic trauma. KEY
WORDS: Delayed diagnosis, Distal pancreatectomy, Pancreatic blunt trauma.
PMID- 29339585
TI - Can ultrasonic surgical devices be used to close the appendicular stump?
AB - : Laparoscopic appendectomy is increasingly being performed because of its quick
recovery time, low instance of wound infection, and early return of patients to
home and work. Operating time should be short yet safe. Therefore, in this study,
we compared the effects of various sealing systems on the length of surgery and
examined whether these systems could be used to separate the appendix from its
stump successfully. This prospective and randomized ex vivo study was conducted
on 20 consecutive patients diagnosed with acute appendicitis. All patients
underwent classical open appendectomy. The patients were classified into two
groups according to the type of sealing system used. The LigaSure(r) system was
used for coagulation in Group L and the Harmonic(r) system in Group H. After
coagulation, a pressure system was used to evaluate the closure of the appendix.
Results showed that the use of ultrasonic instruments alone to close the
appendiceal stump caused an incomplete closure. KEY WORDS: Appendicular stump,
Laparoscopic appendectomy.
PMID- 29339586
TI - Validation of COLA score for predicting wound infection in patients undergoing
surgery for rectal cancer.
AB - AIM: The purpose of our study was to estimate the incidence of SSI (Surgical site
infection) and the effect of COLA (contamination, obesity, laparotomy and ASA
grade) score on SSI in patients undergoing rectal surgical procedures for rectal
cancer. MATERIAL OF STUDY: A total of 92 patients who underwent operation for
rectum cancer were enrolled in this study. Wound surveillance was performed in
all patients by a staff surgeon identified infected wounds during the hospital
stay, and collected information for up to 30 days after operation. RESULTS: The
overall rate of incisional SSI and organ/space SSI was 22.8% and 7.6%
respectively. Surgical site infection rates were 14.2%, 20.58%, 40.7%, 57.1% for
COLA 1,2,3 and 4 scores respectively. The area under the receiver/ operator
characteristic curve for the score was 0,660. CONCLUSION: COLA scoring systems
predict, with reasonable accuracy, the risk of SSI in rectal cancer patients
undergoing elective rectal surgery. KEY WORDS: COLA score Rectal surgery,
Surgical site infection, Risk prediction, Wound infection.
PMID- 29339587
TI - Microscopically positive (R1) resections do not affect survival in pancreatic
head cancer.
AB - BACKGROUND: Obtaining negative microscopic resection margins (R0) in cephalic
duodenopancreatectomy (CDP) is the gold standard. Resection line involvement at
microscopic histopathological examination (R1) could change prognostic
unfavorable. Regarding R1 resections in CDP (data from the literature show rates
between 20-80%), we considered it necessary to perform a study in Regional
Institute of Gastroenterology and Hepatology "Prof. Dr. O. Fodor'' Cluj-Napoca.
METHODS: Here we present the results of a retrospective study carried out between
January 2012 - December 2013 in our Institute. This study includes 63 patients
with pancreatic head resections for pancreatic cancer. The circumferential soft
tissue margin, the pancreatic transection margin, the bile duct and
duodenum/stomach margins were analyzed. We investigated the incidence of R1 and
its impact on the survival rates after oncologic pancreatic resections using a
nonstandardized pathologic routine protocol. R1 status was defined as the
distance of the tumor from the resection margin of <= 1 mm. RESULTS: Pancreatic
ductal adenocarcinoma (PDAC) was diagnosed in 93.65 %. The R1 rate was 36.5 % (23
cases). The circumferential margins were most commonly involved as R1 (91,3%). No
statistically significant differences were found between patients with R1 to
those with R0 (p >= 0.1) regarding 3-year survival. CONCLUSIONS: Survival for
pancreatic head cancer at 3 years is not influenced by the margins of resection
(R1/R0). Microscopic resection margin involvement is not an independent marker of
survival. KEY WORDS: Circumferential margins, Nonstandardized pathologic
protocol, Pancreatic ductal adenocarcinoma, Positive margins R1 Survival.
PMID- 29339588
TI - Recurrent residual or progressive varicose veins: postoperative long term follow
up of 353 patients.
AB - AIM: This study aimed to evaluate the postoperative incidence of recurrent
varicose veins (vv) and the possibility to differentiate the different types of
recurrence. MATERIAL OF STUDY: Patients who underwent surgery for saphenofemoral
junction (SFJ) incompetence, great saphenous vein (GSV) varicosity and at least
one perforator incompetence and varicosity of tributaries between January 1998
and December 2003 were selected for the study. Surgery consisted in SFJ flush
ligation, GSV stripping, perforator vein ligature, and phlebectomies. Patients
were assessed by detailed interview, clinical examination, and color duplex
imaging after 10 years. The differentiation in recurrent, residual and
progressive vv was done by comparison of the pre-and intraoperative and the
phlebographic documentation in particular with the findings on follow-up..
RESULTS: 353 patients (400 legs) were analyzed at 120 +/- 21 months. At follow up
the vv were classified as recurrent in 23,75%, residual in 23,25%, and
progressive in 21% of cases. Nine patients (1.9%) were reoperated after 70 +/- 33
months, and 17 (3.5%) underwent sclerotherapy during follow-up. CONCLUSIONS:
Recurrent, residual, and progressive vv can be clearly differentiated with the
presented methodology. The authors suggest a revised definition (NEVVAS- new vv
after surgery) because the term recurrent and the known acronyms do not embrace
exactly the three types of vv after surgery. Since residual and many recurrent vv
are due to avoidable technical or tactical errors, it is important to classify
them properly in order to avoid these complications. KEY WORDS: Neovarices,
NEVVAS (New Varicose Veins After Surgery), Neovascularization, Recurrent varicose
veins, Residual varicose veins, Progressive varicose veins.
PMID- 29339589
TI - Patient-perceived outcomes of different anaesthetic techniques in classical
surgical treatment of varicose veins of lower limbs.
AB - AIM OF THE STUDY: To evaluate the effects of spinal or locoregional anaesthesia
versus local tumescent anesthesia during traditional surgical treatment of
saphenous reflux, in terms of pain and postoperative functional recovery.
MATERIALS AND METHODS: From January to December 2014, 195 consecutive
interventions of stripping of the greater saphenous vein for valvular
incompetence were performed. In 114 cases spinal or locoregional anaesthesia was
performed (group 1), in the remaining 81 cases local anaesthesia with the
tumescence technique was carried out (group 2). All patients underwent an
assessment of perceived pain by means of verbal rating scale before and at the
end of surgery, at discharge and after a month. The times of recovery of
ambulation during hospital stay and at the discharge were recorded and use of
analgesic drugs during hospitalization and at home. At the end of the study,
patients were asked to express their approval rating on the type of anaesthesia.
RESULTS: Patients in group 2 experienced mild to moderate intraoperative pain
more frequently than patients in group 1 (p<0.001), while patients in group 1 had
more mild adverse anaesthesia-related events than patients in group 2. Patients
in group 2 had faster recovery of ambulation and earlier discharge than patients
in group 1.Thirty-day results were similar in the two groups; however, patients
in group 2 had a higher degree of satisfaction than patients in group 1 with
regard to the type of anaesthesia (p<0.001) CONCLUSIONS: Both locoregional and
local tumescent anaesthesia are effective and well accepted by the patients, with
similar intra-hospital and 30-day results. KEY WORDS: Great Saphenous Vein, Local
tumescent anaesthesia, Pain, Stripping.
PMID- 29339590
TI - Rectal cancer: factors predicting short outcomes after radical anterior
resection.
AB - AIM: This study analyzes risk factors implicated in postoperative complications
and mortality after anterior resection in rectal cancer. MATERIAL AND METHODS: A
total number of 378 patients with anterior rectal resection, diagnosed with
rectal cancer and admitted at the IIIrd Surgery Clinic, "Octavian Fodor" Regional
Institute of Gastroenterology and Hepatology, Romania, between 2009 and 2016. The
inclusion criteria were anterior rectal resections with curative visa for rectal
cancer. The complications we assessed are the following: anastomotic fistula,
intra-abdominal infections, postoperative bowel obstruction and wound infection.
RESULTS: There was statistical significance regarding male gender, emergency
hospitalization, hypoproteinemia and the resumption of intestinal transit.
Anterior rectal resection of tumors located on the middle rectum was associated
with high rate of anastomotic fistula. Patients with manual suture of anastomosis
developed intraabdominal abscess more frequently. In the multivariate analysis,
hypoproteinemia and a number of lymph nodes >1 remained independently associated
with the occurrence of wound infection. The 30-day mortality rate was 4.8% with
18 deaths and morbidity rate 20.6% with 78 cases. CONCLUSIONS: Major
complications after radical resection for rectal cancer are dependent on multiple
variables such as male patients, those admitted in emergency and patients with
hypoproteinemia. Location of tumor on middle rectum, manual suture of
anastomosis, number of lymph nodes > 1 were associated with high rate of
morbidity. Patients with coronary heart disease and diabetes mellitus didn't had
statistical significance, but the rate of morbidity and mortality remains high in
this groups. KEY WORDS: Complications, Radical anterior resection, Rectal cancer,
Risk factors.
PMID- 29339591
TI - Perineural infiltration as a prognostic factor in surgically treated gallbladder
cancer A single center experience and literature review.
AB - INTRODUCTION: Gallbladder cancer (GBC) is the most incident cancer of the biliary
tract with only 5-13% of the sufferers surviving for five years. The aim of this
study was to evaluate the prognostic role of perineural invasion (PNI) and its
association with several clinicopathological variables in a cohort of surgically
treated patients, and through a comprehensive review of the scientific
literature. MATERIALS AND METHODS: Twenty-five consecutive patients submitted to
curative surgery for GBC from 2008 through 2016 were enrolled. Demographic,
clinical and pathological data were retrieved from medical files, and specimens
were re-examined by two experienced pathologists. The Pubmed database was
searched for articles reporting on perineural infiltration on gallbladder cancer.
RESULTS: Perineural invasion was observed in 14 (56%) cases, and it was more
frequent in higher pathological stages. A statistically significant association
was found with high preoperative serum Ca 19-9 levels. Fourteen (56%) patients
died during the follow-up; survival was lower in patients with perineural
invasion in comparison to those without, but not statistically significant.
Twelve English-language articles reporting on PNI were retrieved and discussed.
CONCLUSIONS: Perineural invasion is associated with higher stage and poorer
survival in surgically treated GBC patients. In patients with locally advanced
GBC resection of the extrahepatic biliary duct and frozen section examination of
the distal stump must be taken into consideration, especially in cases of tumor
arising from the hepatic side of the gallbladder. In cases without residual
disease but with pathological evidence of PNI, a careful follow-up is suggested
to early detect recurrences. KEY WORDS: Adenocarcinoma, Cancer, Gallbladder,
Perineural infiltration, Surgery.
PMID- 29339592
TI - Day surgery in Romania.
AB - AIM: Well know in USA, Australia and then in western European countries, day
surgery is still at the beginning in Romania and eastern European countries. In
this paper we want to analyze the evolution and actual situation of day surgery
in Romania and in County Emergency Hospital Timisoara (CEHT). MATERIAL AND
METHODS: In the implementation of day surgery in our country there were two
distinct periods. Between 2007- 2013 the CEHT negotiated its own day surgery
baskets with Local Health Insurance Company (LHIC). Starting from 2014 until now,
the National Health Insurance Company has established new day surgery baskets
which can be negotiated between CEHT and LHIC. RESULTS: Our study shows that day
surgery in CEHT has had an undulating evolution - after a rising development at
the beginning it stopped for a few years and now it has an ascendant evolution.
DISCUSSION: In this context, International Association for Ambulatory Surgery
(IAAS) has initiated a series of actions to support implementation and
development of day surgery in Romania and Eastern European countries. The first
action was the support that the International Association for Ambulatory Surgery
gave to the Romanian Society of Ambulatory Surgery in organizing on 15-16
September 2013 in Timisoara the course "Day Surgery - Making it Happen Overcoming
Obstacles and Barriers". Discussions after the presentation of local realities in
Eastern and Western Europe were particularly creative, being the stand in the
accelerated development of day surgery in Romania. CONCLUSIONS: Day surgery and
ambulatory surgery have many advantages for patients (increased comfort, lower
surgical risk, minimal stress and low anxiety, high satisfaction rate), for
hospital (reducing congestion in hospital, enabling it to have a better capacity
to deal with serious cases), and for healthcare (increased economic efficiency,
cost / patient / surgery is lower than for continuous admissions). Known in our
country from 2000, the implementation of day surgery still faces many hardships.
KEY WORDS: Day surgery, ambulatory surgery, Short hospitalization.
PMID- 29339593
TI - The prognostic role of tumor size in patients with gastric cancer.
AB - AIM: The identification of prognostic factors in gastric cancer is important for
predicting patients' survival and determining therapeutic strategies. MATERIALS
OF STUDY: A retrospective analysis ofpatients who underwent surgery for gastric
cancer between 1996 and 2010. The appropriate cut-off value of tumor size related
to survival was determined using receiver-operating characteristic (ROC) curves
and it was 2,5 cm. Patients were divided into three groups: a small size group
(SSG, < 2,5 cm), a medium size group (MSG, between 2,5 and 5 cm) and a large size
group (LSG, >= 5 cm). RESULTS: Depth of invasion and lymph node metastasis
resulted significantly related to tumor size (p < 0.05). Kaplan- Meier survival
curves showed that OS rate was significantly higher in SSG patients. The
prognosis of patients with tumor size < 2,5 cm was better than patients with
tumors >= 2.5 cm in size (p < 0.01). DISCUSSION: The tumor size resulted
significantly related to OS and it was related to depth of invasion and lymph
node metastasis that are themselves prognostic factors. These results confirm and
reinforced literature and suggest that at diagnostic pre-operative work-up we can
yet define a prognostic value based on tumor size and underline the primary role
of complete resection with free surgical margins and D2 lymphadenectomy.
CONCLUSION: In patients with gastric cancer tumor size suggests information about
the malignancy of the tumor: it is an important predictor of survival and 2,5 cm
may be considered as a valid cut-off to define a better or worse prognosis. KEY
WORDS: Gastric cancer, Prognosis,Survival, Tumor size.
PMID- 29339594
TI - The effects of Crenotherapy and exercise in peripheral arterial occlusive
disease. A comparison with simple exercise training.
AB - BACKGROUND: Conservative therapies for patients affected by Peripheral Arterial
Occlusive Disease (PAOD) aim first to correct the risk factors and to slow down
the disease progression. Among these, exercise has positive effects on blood
flow, muscle metabolism and well demonstrated systemic effects. These include
reduction of chronic inflammation markers, improvement of walking mechanics and
heart function. Controlled physical training increases the ability to perform the
daily activities improving life expectancy of these patients. The aim of this
study is to evaluate the effects and the effectiveness of physical training
performed in thermal water compared to traditional treadmill walking exercise.
METHODS: 98 patients affected by IIb stage PAOD, according to Leriche-Fontaine
classification, were enrolled. Patients were randomized into two groups: the
first arm carried out an intensive training program under medical supervision
(group A); the second one carried out a rehabilitative exercise associated with
crenotherapy (group B). The following parameters were detected: Ankle-Brachial
pressure index (ABI), actual claudication distance (ACD), maximum walking
distance (MWD), flow mediated dilatation (FMD) and the intima-media thickness
(IMT). All patients underwent Doppler echocardiography and complete biochemical
assay. RESULTS: In both groups, there was a statistically significant improvement
of lipidaemia compared to baseline. When compared with each other, the two groups
did not show statistically significant differences. There were no significant
differences between the two groups regarding echocardiographic findings. Vascular
reactivity study showed a statistically significant improvement of FMD after 3
months of exercise in both groups. In crenotherapy group (B) FMD values were
significantly higher than the treadmill ones (A). In both groups a statistically
significant improvement in ACD was observed CONCLUSIONS: Our experience shows
that crenotherapy has similar effects compared to traditional physical training
in the treatment of PAOD, being equally well tolerated and safe; it gives an
advantage over conventional physical training in terms of ACD and MWD
improvement, although not statistically significant, and it is extremely welcome
to patients compared to traditional physical training. KEY WORDS:
Arterioscleroses, Intermittent Claudicatio, Peripheral Arterial Diseasen,
Physical Exercise, Rehabilitation.
PMID- 29339595
TI - Surgical outcomes in patients with hepatic synchronous and metachronous
colorectal metastases.
AB - AIM: To evaluate the impact of several clinical and pathological factors on the
outcomes of surgery for hepatic colorectal cancer metastasis. METHODS: Eighty
four liver metastasectomies in 77 consecutive patients with 90 colorectal cancer
hepatic metastases were performed in our institution from 2009 to 2014. Surgery
was carried out in 75 cases, as two patients were not eligible for surgery. Among
them 43 (Group A) were affected by synchronous, and 32 (Group B) by metachronous
lesions. Furthermore, 9 reoperations were performed in patients with initially
synchronous lesions. The follow-up after surgery included total body CT scan
every 3 months for the first year, and every 6 months for 4 years thereafter.
Blood level of CEA was determined every 3 months. RESULTS: The univariate
analysis evidenced significantly more recurrences in patients with synchronous
lesions (p=0.011), and higher grade, pN stage and CEA blood levels. In
multivariate logistic regression analysis the statistically significant
parameters found were: the pT stage (OR: 3.92, p = 0.039), the use of adjuvant
chemotherapy for the colonic tumor (OR: 0.19, p = 0.025), and the adjuvant
chemotherapy (OR: 4.11, p = 0.048). The global survival was 32 patients (41.5%),
17 with synchronous and 15 with metachronous lesions, and a significant
difference in long-term survival between these two groups was found (p = 0.008).
CONCLUSIONS: The most relevant prognostic factor in patients with hepatic
colorectal cancer dissemination is the timing of metastasis; the metachronous
lesions present better survival when surgically treated. KEY WORDS: Colorectal
cancer, Liver, Metastasis, Surgery.
PMID- 29339596
TI - Is ultrasound a reliable diagnostic tool for acute appendicitis? A single centre
experience.
AB - AIM: Aim of the present study is to evaluate the utility of US as a diagnostic
method for acute appendicitis (AA) in a district general hospital, by use of
accurate quality indices. MATERIAL AND METHODS: The records of all patients who
underwent an appendicectomy in a one year period in a single centre were
reviewed. The patients who underwent a preoperative US scan were included in the
study in accordance to specific criteria and the results were statistically
compared to the final surgical histology. RESULTS: 137 patients who underwent an
US were included in the study, with 69 patients (23%) presenting a negative
histology result. Overall, the US results correlated statistically significantly
with the final histology results, with a specificity of 0.87, a sensitivity of
0.34 and an overall diagnostic accuracy of 0.51. DISCUSSION: The results of the
study are comparable with the reported literature, presenting high specificity
but a relatively low sensitivity, although great variability exists in the
literature. US seems useful in confirming rather than excluding AA. CONCLUSION:
In view of its advantages, the incorporation of ultrasonography into routine
clinical practice when performed by an expert is recommended, but only in support
of other diagnostic elements. The issue of low sensitivity should be further
addressed. KEY WORDS: Appendicectomy, Diagnostic accuracy, Histology.
PMID- 29339597
TI - Unexpected findings in the routine histopathological examinations of appendectomy
specimens A retrospective analysis of 1,970 patients.
AB - INTRODUCTION: Diseases and tumors of the appendix vermiformis are very rare,
except for acute appendicitis. This study aimed to examine rare findings in the
histopathologic examinations of specimens of patients undergoing appendectomy due
to the diagnosis of acute appendicitis. METHODS: The files of 1,970 patients
undergoing appendectomy due to the diagnosis of acute appendicitis between March
2012 and March 2016 were retrospectively investigated. Rare findings were found
in 59 (3%) patients, and these were evaluated in detail. Patients' age, gender,
pathology reports, and post-operation follow-ups were recorded. RESULTS: The rare
histopathological findings of 59 patients were examined. Of these, 31 were female
(52.5%) and 28 were male (47.5%). The average age was 33.1+/-18.2 years. The
unusual findings were as follows: 16 Fibrous obliteration, 11 Enterobius
vermicularis, 2 Schistosomiasis, 3 Appendiceal neuroma, 2 Granulomatous
appendicitis, 1 Crohn's disease, 3 Chronic appendicitis, 1 Endometriosis, 2
Hyperplastic polyps, 9 Mucinous cystadenoma (+mucocele), 8 Carcinoid tumors and 1
Lymphoma. All of the malignant tumors were localized in the distal end of the
appendix and all of the patients were treated with appendectomy. Patients with
parasitic diseases also underwent anthelmintic treatment, while chemotherapy was
administered to the patient with lymphoma. All of the patients diagnosed with
malignancy were alive reported no problems at their follow-ups. CONCLUSION:
Although all of the appendectomy samples were normal macroscopically, data from
this study suggest that all specimens should be sent for routine investigation.
KEY WORDS: Appendicitis, Appendectomy, Carcinoid, Mucocele, Endometriosis.
PMID- 29339598
TI - Design parameter estimations for adjustable bubble size in bubble generating
system.
AB - In this study, we developed a customized low cost and low energy bubble generator
that can control bubble size. Hence, it can be used not only in the water
treatment process but also in various other processes. This device was able to
generate bubbles with a very simple system using only a general pump and a mixing
chamber. Increasing the number of partition walls in the mixing chamber reduced
the bubble size. Furthermore, bubbles of a few hundred nanometers were produced
by the shear stress caused by increasing the thickness of the partition wall.
Although the generated sub-micron bubbles were too small for their exact size to
be measured using an image analysis and particle counting method, it was possible
to confirm their existence indirectly through the coalescence arising from
ultrasonic irradiation. The device used in this research is simple and allows
bubble size to be adjusted easily by controlling the design of the mixing
chamber. Therefore, it can be applied to a water treatment process, as well as a
variety of other processes.
PMID- 29339599
TI - Full-scale performance of selected starch-based biodegradable polymers in sludge
dewatering and recommendation for applications.
AB - Agricultural reuse of dewatered sludge is a valid route for sludge valorization
for small and mid-size wastewater treatment plants (WWTPs) due to the direct
utilization of nutrients. A more stringent of German fertilizer ordinance
requires the degradation of 20% of the synthetic additives like polymeric
substance within two years, which came into force on 1 January 2017. This study
assessed the use of starch-based polymers for full-scale dewatering of municipal
sewage sludge. The laboratory-scale and pilot-scale trials paved the way for full
scale trials at three WWTPs in Germany. The general feasibility of applying
starch-based 'green' polymers in full-scale centrifugation was demonstrated.
Depending on the sludge type and the process used, the substitution potential was
up to 70%. Substitution of 20-30% of the polyacrylamide (PAM)-based polymer was
shown to achieve similar total solids (TS) of the dewatered sludge. Optimization
of operational parameters as well as machinery set up in WWTPs is recommended in
order to improve the shear stability force of sludge flocs and to achieve higher
substitution potential. This study suggests that starch-based biodegradable
polymers have great potential as alternatives to synthetic polymers in sludge
dewatering.
PMID- 29339600
TI - Scaling up and kinetic model validation of Direct Black 22 degradation by
immobilized Penicillium chrysogenum.
AB - This research was undertaken to develop tools that facilitate the industrial
application of an immobilized loofah-fungi system to degrade Direct Black 22
(DB22) azo dye. In laboratory-scale tests, the DB22, and loofah as support, were
used. Assays without loofah were used as a free-cells control. The use of natural
carriers to facilitate adhesion and growth of the fungi has shown favorable
results. The degradation rate of immobilized cells increased twice as compared to
free-cells control. At day 5 the decolorization was almost complete, while
without loofah the total decolorization took more than 10 days. After 10 days,
the extent of growth was nine times higher for the immobilized assays in
comparison with the control flask. In subsequent experiments decolorization of
DB22 was proven in a bench-scale reactor. A previously developed kinetic model
was validated during the process. The model validation over free-cells assays
gives an average normalized root mean squared error (ANRMSE) of 0.1659.
Recalibration steps allowed prediction of the degradation with immobilized cells,
resulting in an ANRMSE of 0.1891. A new calibration of the model during the
scaling-up process yielded an ANRMSE of 0.1136 for DB22. The results presented
encourage the use of this modeling tool in industrial scale facilities.
PMID- 29339601
TI - Ammonium removal in landfill leachate using SBR technology: dispersed versus
attached biomass.
AB - Large concentrations and oscillations of ammonium nitrogen (NH4+-N) in municipal
landfill leachate pose considerable constraints to its further treatment in
central wastewater treatment plants. The aim of this study was to evaluate and
optimize two technologies for the pre-treatment of 600 L/day of landfill
leachate: in particular, to optimize their operational conditions for NH4+-N
removal up to a level appropriate for discharge to sewers, i.e. <200 mg/L. Both
technologies were based on a sequencing batch reactor (SBR), with two different
biomass processes: (A) SBR with dispersed/flocculated biomass and (B) SBR with
biomass attached to carriers. The results revealed that both technologies
successfully reduced the NH4+-N from 666 mg/L (on average) at the inflow to below
10 mg/L at the outflow with alkalinity adjustment in a 12-hour cycle. Both
technologies achieved 96% removal efficiencies for NH4+-N. However, SBR with
dispersed biomass showed higher flexibility under varying conditions due to the
shorter adaptation time of the biomass.
PMID- 29339602
TI - Performance and stability of an expanded granular sludge bed reactor modified
with zeolite addition subjected to step increases of organic loading rate (OLR)
and to organic shock load (OSL).
AB - This paper shows the effect of organic shock loads (OSLs) on the anaerobic
digestion (AD) of synthetic swine wastewater using an expanded granular sludge
bed (EGSB) reactor modified with zeolite. Two reactors (R1 and R2), each with an
effective volume of 3.04 L, were operated for 180 days at a controlled
temperature of 30 degrees C and hydraulic retention time of 12 h. In the case of
R2, 120 g of zeolite was added. The reactors were operated with an up-flow
velocity of 6 m/h. The evolution of pH, total Kjeldahl nitrogen, chemical oxygen
demand (COD) and volatile fatty acids (VFAs) was monitored during the AD process
with OSL and increases in the organic loading rate (OLR). In addition, the
microbial composition and changes in the structure of the bacterial and archaeal
communities were assessed. The principal results demonstrate that the presence of
zeolite in an EGSB reactor provides a more stable process at higher OLRs and
after applying OSL, based on both COD and VFA accumulation, which presented with
significant differences compared to the control. Denaturing gradient gel
electrophoresis band profiles indicated differences in the populations of
Bacteria and Archaea between the R1 and R2 reactors, attributed to the presence
of zeolite.
PMID- 29339603
TI - Simultaneous organic matter removal and nitrification of an inert self-supporting
immersed media to upgrade aerated lagoons.
AB - A pilot study was performed to evaluate the potential of an inert self-supported
immersed fixed film media to upgrade aerated lagoons. Simultaneous organic matter
removal and nitrification was assessed under different loading rates and
temperatures (near 0 degrees C) using 12 laboratory-scale reactors operated in
parallel. Test results showed that both the temperature and the load have an
influence on organic matter effluent concentrations. Effluent quality seemed
related to the observed biofilm thickness. Thicker biofilm is believed to have
contributed to biomass detachment and increased particulate organic matter
concentrations in the effluent. Simultaneous organic removal and nitrification
was obtained at loads above 5 g CBOD5/m2.d. The highest nitrification rate at 0.4
degrees C was obtained for the smallest load, which showed a nitrification
limitation close to freezing point.
PMID- 29339604
TI - Modeling biosorption of Cr(VI) onto Ulva compressa L. from aqueous solutions.
AB - The marine biomass Ulva compressa L. (ECL) was used as a low-cost biosorbent for
the removal of Cr(VI) from contaminated aqueous solutions. The operating
variables were optimized: pH ~ 2, initial concentration of 25 mg/L, solid/liquid
ratio of 6 g/L and a temperature of 50 degrees C, leading to an uptake
elimination of 96%. A full factorial experimental design technique enabled us to
obtain a mathematical model describing the Cr(VI) biosorption and to study the
main effects and interactions among operational parameters. The equilibrium
isotherm was analyzed by the Langmuir, Freundlich and Dubinin-Radushkevich (D-R)
models; it has been found that the adsorption process follows well the Langmuir
model. Kinetic studies showed that the pseudo-second order model describes
suitably the experimental data. The thermodynamic parameters indicated an
endothermic heat and a spontaneity of the Cr(VI) biosorption onto ECL.
PMID- 29339605
TI - Enhancing nitrogen removal efficiency in a dyestuff wastewater treatment plant
with the IFFAS process: the pilot-scale and full-scale studies.
AB - The activated sludge (AS) process is widely applied in dyestuff wastewater
treatment plants (WWTPs); however, the nitrogen removal efficiency is relatively
low and the effluent does not meet the indirect discharge standards before being
discharged into the industrial park's WWTP. Hence it is necessary to upgrade the
WWTP with more advanced technologies. Moving bed biofilm processes with suspended
carriers in an aerobic tank are promising methods due to enhanced nitrification
and denitrification. Herein, a pilot-scale integrated free-floating biofilm and
activated sludge (IFFAS) process was employed to investigate the feasibility of
enhancing nitrogen removal efficiency at different hydraulic retention times
(HRTs). The results showed that the effluent chemical oxygen demand (COD),
ammonium nitrate (NH4+-N) and total nitrogen (TN) concentrations of the IFFAS
process were significantly lower than those of the AS process, and could meet the
indirect discharge standards. PCR-DGGE and FISH results indicated that more
nitrifiers and denitrifiers co-existed in the IFFAS system, promoting
simultaneous nitrification and denitrification. Based on the pilot results, the
IFFAS process was used to upgrade the full-scale AS process, and the effluent
COD, NH4+-N and TN of the IFFAS process were 91-291 mg/L, 10.6-28.7 mg/L and 18.9
48.6 mg/L, stably meeting the indirect discharge standards and demonstrating the
advantages of IFFAS in dyestuff wastewater treatment.
PMID- 29339606
TI - Study of aggregation in surface sludge deposits from 14 full-scale French
constructed wetlands using particle size distribution and dynamic vapor sorption
analyses.
AB - French vertical flow constructed wetlands (French VFCWs) are widely used for the
treatment of wastewaters from small communities. In the system, unsettled
wastewater is percolated through two successive stages of filter-cells planted
with reeds. This causes the formation of a surface sludge layer. This layer plays
positive roles in the treatment performance, but also leads to clogging. The
objective of this study was to contribute to the description of the sludge
deposits characteristics and their dynamics of evolution, which may control the
development of clogging. Representative samples of sludge deposits were taken
from 14 French VFCWs full-scale plants and analyzed for particle size, dynamic
vapor sorption and other parameters of composition to compare their structure and
evaluate the factors of influence. Results showed that ageing of the surface
deposits layer over the years of operation in each plant induced the formation
and integration of microaggregates within the initial macrostructure of fresh
organic matter (OM). The humification process of the OM was found to play a key
role in the aggregation process. The injection of FeCl3 operated to precipitate
phosphates before filtration was found to accelerate the aggregation process in
the early phase (<1 year) of operation of the sludge.
PMID- 29339607
TI - Batch and fixed-bed column study for p-nitrophenol, methylene blue, and U(VI)
removal by polyvinyl alcohol-graphene oxide macroporous hydrogel bead.
AB - There is an increasing need to explore effective and clean approaches for
hazardous contamination removal from wastewaters. In this work, a novel bead
adsorbent, polyvinyl alcohol-graphene oxide (PVA-GO) macroporous hydrogel bead
was prepared as filter media for p-nitrophenol (PNP), dye methylene blue (MB),
and heavy metal U(VI) removal from aqueous solution. Batch and fixed-bed column
experiments were carried out to evaluate the adsorption capacities of PNP, MB,
and U(VI) on this bead. From batch experiments, the maximum adsorption capacities
of PNP, MB, and U(VI) reached 347.87, 422.90, and 327.55 mg/g. From the fixed-bed
column experiments, the adsorption capacities of PNP, MB, and U(VI) decreased
with initial concentration increasing from 100 to 400 mg/L. The adsorption
capacities of PNP, MB, and U(VI) decreased with increasing flow rate. Also, the
maximum adsorption capacity of PNP decreased as pH increased from 3 to 9, while
MB and U(VI) presented opposite tendencies. Furthermore, the bed depth service
Time (BDST) model showed good linear relationships for the three ions' adsorption
processes in this fixed-bed column, which indicated that the BDST model
effectively evaluated and optimized the adsorption process of PVA-GO macroporous
hydrogel bead in fixed-bed columns for hazardous contaminant removal from
wastewaters.
PMID- 29339608
TI - Pilot study of oilfield wastewater treatment by micro-flocculation filtration
process.
AB - In order to meet the latest Environmental Protection Law of China on wastewater
discharge standards, this paper studied a pilot-scale micro-flocculation
filtration pretreatment process for the treatment of oilfield wastewater. The
experiment showed that the removal rate of oil and suspended solids (SS)
respectively increased from 91.52% to 95.38% and from 66.42% to 97.19%. After the
treatment by the micro-flocculation filtration device, the relevant
characteristics of the discharge wastewater satisfied the latest standards
continuously. Moreover, the polyaluminum chloride (PAC) dosage was reduced from
200 mg/L to 100 mg/L (50 mg/L in micro-flocculation device and 50 mg/L in the
cyclone reactor) at the same time. In order to decrease the degree of scaling in
the filter, ceramsite was chosen as the filter material instead of quartz sand
that is widely applied in the oilfields. The scaling experiment showed that the
HCO3-, Ca2+ and Mg2+ contents in the extract from quartz sand after the scaling
study were increased by 38.05, 35.91 and 0.28 mg/L, respectively. Meanwhile, the
HCO3-, Ca2+ and Mg2+ contents in the extract from ceramsite were only increased
by 13.14, 6.26 and 0.27 mg/L, respectively. Therefore, the ceramsite is not so
prone to scaling as compared to quartz sand under identical test conditions,
which avoided a hardened and impervious filter after operating for some time.
These results suggest that the micro-flocculation filtration with the ceramsite
as filter media is a suitable pretreatment process for the oilfield wastewater
treatment.
PMID- 29339609
TI - Effects of pH and coexisting chemicals on photolysis of perfluorooctane sulfonate
using an excited xenon dimer lamp.
AB - Vacuum ultraviolet (VUV) photolysis at the wavelength of 172 nm in a sulfate
solution was introduced as a more efficient process for perfluorooctane sulfonate
(PFOS) degradation than ultraviolet (UV) photolysis at 254 nm. The effects of pH
and coexisting chemicals on VUV photolysis under the coexistence of 100 mM
sulfate were investigated. VUV irradiation successfully degraded PFOS, and the
degradation rate was 5.5 times higher than by UV photolysis. Direct VUV
photolysis was inferred to mainly contribute to PFOS degradation. PFOS
degradation by VUV irradiation was enhanced at pH less than 2 due to sulfate
radicals generated via VUV photolysis of sulfate ions. Consequently, VUV
photolysis was superior to UV photolysis for PFOS removal on both the removal
rate and energy efficiency. However, the inorganic chemicals phosphoric acid and
nitric acid strongly inhibited PFOS degradation, probably by masking PFOS from
VUV rays by their VUV absorption. Accordingly, PFOS separation from inorganic
materials such as phosphate and nitrate will be recommended for the application
of VUV techniques for PFOS removal. In this research, organic solvent abstraction
was inferred to be one of candidates for PFOS separation.
PMID- 29339610
TI - Effect of precursor type on the reduction of concentrated nitrate using zero
valent copper and sodium borohydride.
AB - In this study, we demonstrated that the choice of precursor has a strong effect
on the reduction of nitrate (NO3-) using zero-valent copper (Cu0) synthesized by
sodium borohydride (NaBH4). Different precursors: CuSO4, CuO, Cu2O, Cu powder,
and Cu mesh were used to reduce NO3- at 677 mg-N/L under the reducing conditions
of NaBH4. Compared with the prehydrolyzed samples, those prepared without
prehydrolysis exhibited lower reduction rates, longer times and higher
concentrations of nitrite (NO2-) intermediate. It was found that one-time
addition of NaBH4 resulted in higher reduction rate and less NO2- intermediate
than two-step addition. Results showed that Cu0 from CuSO4 possessed the smallest
particle size (890.9 nm), highest surface area (26.0 m2/g), and highest reaction
rate (0.166 min-1). Values of pseudo-first-order constant (kobs) were in the
order: CuSO4 > CuO > Cu2O > Cu powder >Cu mesh. However, values of surface area
normalized reaction rate (kSA) were approximately equal. It was proposed that NO3
was reduced to NO2- on Cu0, and then converted to NH4+ and N2, respectively; H2
generated from both NaBH4 hydration and Cu (II) reduction contributed to NO3-
reduction as well.
PMID- 29339611
TI - Mechanism of 1,4-dioxane microbial degradation revealed by 16S rRNA and
metatranscriptomic analyses.
AB - 1,4-Dioxane (dioxane), a probable human carcinogen, often exists in industrial
wastewater and domestic sewage. In this study, we applied 16S rRNA and
metatranscriptomic methods to analyze the dioxane biodegradation mechanism by
activated sludge. Tetrahydrofuran (THF) was added as an essential co-metabolite
to promote the degradation of dioxane. We found the dioxane removal ratio
increased with increasing THF concentrations. When the THF concentration
increased from 60.0 to 200.0 mg/L, the dioxane degradation rate was stable. Three
additions of ~60.0 mg/L THF resulted in better dioxane degradation than one
addition of 200 mg/L THF. Ammonia-oxidizing and denitrifying bacteria with
methane monooxygenases (MOs) and ammonia MOs played the most important roles
during the degradation of dioxane. Kyoto Encyclopedia of Genes and Genomes
metabolic pathway and functional genes analyses showed that the activated sludge
system was complex and stable when dioxane was added. In future studies, primers
should be designed to identify specific bacteria and functional MO genes, which
would help reveal the function of various bacteria and their MOs during dioxane
degradation.
PMID- 29339612
TI - Industrial wastewater treatment with a bioelectrochemical process: assessment of
depuration efficiency and energy production.
AB - Development of renewable energy sources, efficient industrial processes,
energy/chemicals recovery from wastes are research issues that are quite
contemporary. Bioelectrochemical processes represent an eco-innovative technology
for energy and resources recovery from both domestic and industrial wastewaters.
The current study was conducted to: (i) assess bioelectrochemical treatability of
industrial (dairy) wastewater by microbial fuel cells (MFCs); (ii) determine the
effects of the applied organic loading rate (OLR) on MFC performance; (iii)
identify factors responsible for reactor energy recovery losses (i.e.
overpotentials). For this purpose, an MFC was built and continuously operated for
72 days, during which the anodic chamber was fed with dairy wastewater and the
cathodic chamber with an aerated mineral solution. The study demonstrated that
industrial effluents from agrifood facilities can be treated by
bioelectrochemical systems (BESs) with >85% (average) organic matter removal,
recovering power at an observed maximum density of 27 W m-3. Outcomes were better
than in previous (shorter) analogous experiences, and demonstrate that this type
of process could be successfully used for dairy wastewater with several
advantages.
PMID- 29339613
TI - Sorption of Cr, Pb, Cu, Zn, Cd, Ni, and Co to nano-TiO2 in seawater.
AB - In this study, the role of nanoparticles in complex aqueous matrices such as the
Baltic Sea was investigated in batch-mode experiments in which titanium dioxide
nanoparticles (nano-TiO2) were tested for their ability to remove heavy metals
(Cr, Pb, Cu, Zn, Cd, Ni, Co) from multicomponent spiked and non-spiked Baltic Sea
water. The experimental data were analyzed using different isotherms (Langmuir,
Freundlich, Dubinin-Kaganer-Radushkevich (DKR)) and models (pseudo-first-order
and pseudo-second-order models, the double-exponential model, and the Weber
Morris model). The equilibria and kinetic investigations showed that metal
sorption to nano-TiO2 occurs in a two-step, multilayer process and that there is
strong competition for sorption sites. The results of the DKR isotherm and
dilution experiment indicated weak electrostatic bonds, except for Pb. The
distribution coefficient values (1.8 * 103 to 2.8 * 105 ml g-1) were consistent
with the good sorbent properties of nano-TiO2 and supported the use of the
particles in seawater purification technologies. However, metal-enriched nano
TiO2 may also act as an effective carriers of metals to marine sediments, which
could increase their availability to benthic organisms.
PMID- 29339614
TI - Application of image processing on struvite recovery from swine wastewater by
using the fluidized bed.
AB - Fluidized granulation is one of the common methods used in wastewater treatment
and resource recovery with harvesting millimeter-scale large particles.
Presently, effective methods are lacking to measure the fluidized granules
ranging from micro- to millimeter scales, with the consequence of ineffectively
controlling and optimizing the granulation process. In this work, recovering
struvite (MgNH4PO4.6H2O) from swine wastewater by using a fluidized bed was taken
as an example. Image processing was applied to analyze the properties of
different types of struvite granules, including morphology, particle size
distribution, number density and mass concentration. Four stages of the struvite
crystal evolution were therefore defined: aggregation, aggregate compaction,
cluster-agglomerating and coating growth. These stages could occur simultaneously
or sequentially. Up-flow rates of 30-80 mm/s in the fluidized bed sustained 600
876 g/L granular solids. Results revealed that the coating-growth granules were
formed with compact aggregates or cluster-agglomerating granules as the nuclei.
The growth rates for the different types of particles, including population
growth, mass increase and particle size enlargement, were determined. In final, a
schematic illustration for struvite granulation process is also presented.
PMID- 29339615
TI - Adsorption performance of polydopamine-modified attapulgite granular adsorbent
for methylene blue.
AB - Polydopamine-modified granule organo-attapulgite adsorbent (PDA-GOAT) was
facilely prepared via a dip-coating approach. The samples were characterized by
scanning electron microscopy, X-ray photoelectron spectroscopy and Fourier
transform infrared spectroscopy. Surface area and pore size were calculated from
the Brunauer-Emmett-Teller method by N2 adsorption-desorption isotherm. The
adsorption behaviour of methylene blue (MB) onto PDA-GOAT was systematically
investigated. The experimental data revealed that the adsorption process fitted
well with the pseudo-second-order kinetics equation and the adsorption isotherm
fitted better with the Langmuir model. Thermodynamic analyses illustrated that MB
adsorption onto PDA-GOAT was a physisorption endothermic process. Importantly,
PDA-GOAT can be regenerated by NaBH4 aqueous solution. The obtained results prove
that PDA-GOAT can be a superior reusable adsorbent for the removal of MB from
effluent.
PMID- 29339616
TI - COD removal from leachate by electrocoagulation process: treatment with monopolar
electrodes in parallel connection.
AB - This study examines the removal of chemical oxygen demand (COD) from landfill
leachate generated from the municipal landfill site of Bingol, Turkey. The effect
of parameters such as current density, pH, and inter-electrode distance during
the electrocoagulation (EC) process on COD removal of the process was
investigated. Moreover, for COD removal, the energy consumption and operating
costs were calculated for iron electrode under the EC conditions. COD removal
efficiency was 72.13% at the current density of 16 mA m-2, pH of 8.05, and the
inter-electrode distance of 9 mm at the detention time of 60 min with iron
electrode and the COD concentration was reduced from 6,100 mg L-1 to 1,700 mg L-1
by EC. The highest value of the electrical energy and electrode consumptions per
kg of COD in the optimum conditions were determined as 0.055 kWh kg-1 COD and
3.43 kg kg-1 COD and the highest operating cost value was found to be 1.41 US$ kg
1 COD for 0-60 min time intervals.
PMID- 29339617
TI - Characteristics of N2O production and hydroxylamine variation in short-cut
nitrification SBR process.
AB - In order to study the characteristics of nitrous oxide (N2O) production and
hydroxylamine (NH2OH) variation under oxic conditions, concentrations of NH2OH
and N2O were simultaneously monitored in a short-cut nitrification sequencing
batch reactor (SBR) operated with different influent ammonia concentrations. In
the short-cut nitrification process, N2O production was increased with the
increasing of ammonia concentration in influent. The maximum concentrations of
dissolved N2O-N in the reactor were 0.11 mg/L and 0.52 mg/L when ammonia
concentrations in the influent were 50 mg/L and 70 mg/L respectively. Under the
low and medium ammonia load phases, the concentrations of NH2OH-N in the reactor
were remained at a low level which fluctuated around 0.06 mg/L in a small range,
and did not change with the variation of influent NH4+-N concentration. Based on
the determination results, the half-saturation of NH2OH in the biochemical
conversion process of NH2OH to NO2--N was very small, and the value of 0.05 mg
NH2OH-N/L proposed in the published literature was accurate. NH2OH is an
important intermediate in the nitrification process, and the direct determination
of NH2OH in the nitrification process was beneficial for revealing the kinetic
process of NH2OH production and consumption as well as the effects of NH2OH on
N2O production in the nitrification process.
PMID- 29339618
TI - Rheological and electrical properties used to investigate the coagulation process
during sludge treatment.
AB - Analyses of rheological properties and electrical conductivity (sigmadc) at
direct current have been employed in order to investigate the effects of calcium
oxide on the coagulation process during sludge treatment in the textile industry.
In this context, rheological and electrical measurements were performed on five
samples - one that contained raw sludge and the other four that were prepared
from the raw sludge and different amounts of calcium oxide: 2, 3, 4, 5% (w/w).
Rheological behavior of these samples was analyzed using the Herschel-Bulkley
modified model. The influence of calcium oxide content on the rheological
parameters such as infinite viscosity, the yield stress, the consistency
coefficient, and the consistency index, are presented and discussed. The impact
of the calcium oxide content on pH and conductivity were also examined. Similar
behaviors have been seen in the evolution of conductivity and infinite viscosity
as a function of the calcium oxide content. These latter characteristics were
modeled by an equation using two power laws. This equation was able to fit very
well the evolution of electrical conductivity and also the viscosity versus the
percentage of calcium oxide to predict the optimal amount of calcium oxide (3%)
to achieve the coagulation step during sludge treatment.
PMID- 29339619
TI - Improved sludge dewaterability and hydrolysis performance after pretreatment with
Fenton's reagent.
AB - The dewaterability of excess sludge significantly improved upon pretreatment with
Fenton's reagent in this study. After 0.9 g/L of Fe2+ and 5.0 g/L of H2O2 were
added to the sludge, and reacted for 2 h at pH = 4, the specific resistance to
filtration (SRF) of the excess sludge decreased from an initial value of 29.74 *
1012 m/kg to 6.49 * 1012 m/kg. The factors that affected this improvement in
sludge dewaterability as evaluated by SRF reduction showed the following order:
H2O2 > pH > Fe2+ > reaction time. Furthermore, the hydrolysis performance of the
sludge under the optimal reaction conditions was investigated. The results
indicated that the concentration of soluble chemical oxygen demand in the
supernatant increased almost 14 times compared to raw sludge, and the contents of
soluble protein and soluble polysaccharide were more than 8 and 17 times higher,
respectively, than for the untreated situation. However, the amounts of ammonia
nitrogen (NH4+-N) and phosphate (PO43--P) released from the sludge showed
different trends: NH4+-N increased by 200%, while PO43--P decreased by 82%. The
production of volatile fatty acids (VFAs) from the treated sludge showed that
total VFAs increased by 66%, and iso-butylacetic acid was the dominant product
among the total VFAs.
PMID- 29339620
TI - The membrane fouling mechanisms of the PAC/BPAC-UF combined process used to treat
the secondary effluent from municipal wastewater treatment plant.
AB - The combined processes of powdered activated carbon/biological powdered activated
carbon- ultrafiltration (PAC/BPAC-UF) were used to treat secondary effluent. In
this study, the effect of PAC and BPAC on membrane flux, membrane resistance and
the removal of different molecular weight organic compounds were investigated. In
addition, the structure characteristics of the microorganisms of the BPAC were
analyzed. The results showed that the optimum dosage of PAC and BPAC was 10 mg/L
and 40 mg/L respectively. The reversible membrane fouling resistance of BPAC-UF
was higher than that of PAC-UF, and the two processes had the least irreversible
resistance at the best dosage. The biodegradation of BPAC increased the
concentration of small molecular weight organic matter up to 10,000 Da in the
membrane effluent. So the dissolved organic carbon (DOC) removal effect of BPAC
UF process worsened. Microorganisms such as Proteobacteria, Bacteroidetes,
Planctomycetes and other microorganisms on the surface of the BPAC enhanced the
removal of organic matter in water. The results of scanning electron microscopy
(SEM) scans showed that there was net mucus membrane on the UF membrane surface
before the backwashing of the BPAC-UF process which increased the proportion of
reversible pollution resistance. The physical flushing effect of BPAC-UF was
better than that of direct UF and PAC-UF processes.
PMID- 29339621
TI - Highly enhanced adsorption of Congo red by functionalized finger-citron-leaf
based porous carbon.
AB - A novel high-performance porous carbon material, lanthanum(III)-doped finger
citron-leaf-based porous carbon (La/FPC), has been synthesized and used as an
adsorbent for anion dye Congo red (CR). The La/FPC was characterized by nitrogen
adsorption and desorption isotherms, scanning electron microscopy, transmission
electron microscopy and X-ray photoelectron spectroscopy. The adsorption
performance of CR by the FPC and La/FPC composites with different contents of
lanthanum(III) were evaluated in fixed-bed breakthrough experiments and batch
tests at room temperature (298 K). The La/FPC had a high CR uptake capacity,
which was superior to those previously reported for other adsorbents. The La/FPC
sorbents can be easily regenerated using an ethanol elution technique, and after
five cycles the reused La/FPC maintained about 98% of its original CR adsorption
capacity. The adsorption kinetics of CR onto the lanthanum(III)-doped FPCs
followed a pseudo-second-order kinetic model and fitted well with a Langmuir
adsorption isotherm. La/FPC is a promising adsorbent for the removal of the
anionic dyes from wastewater.
PMID- 29339622
TI - Identification of fouling mechanisms in MBRs at constant flowrate: model
applications and SEM-EDX characterizations.
AB - A fundamental understanding of fouling mechanisms is critical to improving
filtration operations. The performance of four parallel membrane bioreactors
(MBRs) with different sludge retention times (SRTs) was monitored during long
term constant flowrate filtration. The characteristics of the membrane and
transmembrane pressure (TMP) profiles obtained were studied to demonstrate
fouling mechanisms. Both classical blocking models and their combined models were
evaluated. The intermediate model provided very good agreement with all the TMP
data. However, the combined cake-intermediate and intermediate-standard models
were more effective in the description of the experimental data. Contributions
analysis indicated that the cake, intermediate and standard blocking models were
the dominant fouling mechanisms. Scanning electron microscopy and energy
dispersive X-ray (SEM-EDX) imaging showed that cake blocking by organic matter
and standard blocking by inorganic matter made the main contributions to membrane
fouling. The combined cake-intermediate and intermediate-standard models may be
applicable to systems where these two models are consistent with the
experimentally observed fouling mechanisms in an MBR.
PMID- 29339623
TI - Effects of scale and Froude number on the hydraulics of waste stabilization
ponds.
AB - This paper presents the findings from a series of computational fluid dynamics
simulations to estimate the effect of scale and Froude number on hydraulic
performance and effluent pollutant fraction of scaled waste stabilization ponds
designed using Froude similarity. Prior to its application, the model was
verified by comparing the computational and experimental results of a model
scaled pond, showing good agreement and confirming that the model accurately
reproduces the hydrodynamics and tracer transport processes. Our results showed
that the scale and the interaction between scale and Froude number has an effect
on the hydraulics of ponds. At 1:5 scale, the increase of scale increased short
circuiting and decreased mixing. Furthermore, at 1:10 scale, the increase of
scale decreased the effluent pollutant fraction. Since the Reynolds effect cannot
be ignored, a ratio of Reynolds and Froude numbers was suggested to predict the
effluent pollutant fraction for flows with different Reynolds numbers.
PMID- 29339624
TI - The combined effects of carbon/nitrogen ratio, suspended biomass, hydraulic
retention time and dissolved oxygen on nutrient removal in a laboratory-scale
anaerobic-anoxic-oxic activated sludge biofilm reactor.
AB - The current trend in sustainable development deals mainly with environmental
management. There is a need for economically affordable, advanced treatment
methods for the proper treatment and management of domestic wastewater containing
excess nutrients (such as nitrogen and phosphorus) which can cause
eutrophication. The reduction of the excess nutrient content of wastewater by
appropriate technology is of much concern to the environmentalist. In the current
study, a novel integrated anaerobic-anoxic-oxic activated sludge biofilm (A2O-AS
biofilm) reactor was designed and operated to improve the biological nutrient
removal by varying reactor operating conditions such as carbon to nitrogen (C/N)
ratio, suspended biomass, hydraulic retention time (HRT) and dissolved oxygen
(DO). Based on various trials, it was seen that the A2O-AS-biofilm reactor
achieved good removal efficiencies with regard to chemical oxygen demand (95.5%),
total phosphorus (93.1%), ammonia nitrogen concentration (NH4+-N) (98%) and total
nitrogen (80%) when the reactor was maintained at C/N ratio of 4, suspended
biomass of 3 to 3.5 g/L, HRT of 10 h, and DO of 1.5 to 2.5 mg/L. Scanning
electron microscopy (SEM) of suspended and attached biofilm showed a dense
structure of coccus and bacillus bacteria with the diameter ranging from 0.3 to
1.2 MUm. The Fourier transform infrared (FTIR) spectroscopy results indicated
phosphorylated macromolecules and carbohydrates mix or bind with extracellular
proteins in exopolysaccharides.
PMID- 29339625
TI - Acid production potentials of massive sulfide minerals and lead-zinc mine
tailings: a medium-term study.
AB - Weathering of sulfide minerals is a principal source of acid generation. To
determine acid-forming potentials of sulfide-bearing materials, two basic
approaches named static and kinetic tests are available. Static tests are short
term, and easily undertaken within a few days and in a laboratory. In contrast,
kinetic tests are long-term procedures and mostly carried out on site. In this
study, experiments were conducted over a medium-term period of 2 months, not as
short as static tests and also not as long as kinetic tests. As a result, pH and
electrical conductivity oscillations as a function of time, acid-forming
potentials and elemental contents of synthetically prepared rainwater leachates
of massive sulfides and sulfide-bearing lead-zinc tailings from abandoned and
currently used deposition areas have been determined. Although the lowest final
pH of 2.70 was obtained in massive pyrite leachate, massive chalcopyrite leachate
showed the highest titrable acidity of 1.764 g H2SO4/L. On the other hand, a
composite of currently deposited mine tailings showed no acidic characteristic
with a final pH of 7.77. The composite abandoned mine tailing leachate had a
final pH of 6.70, close to the final pH of massive galena and sphalerite
leachates, and produced a slight titrable acidity of 0.130 g H2SO4/L.
PMID- 29339626
TI - Estimation of the dilution field near a marine outfall by using effluent
turbidity as an environmental tracer and comparison with dye tracer data.
AB - The alternative use of effluent turbidity to determine the dilution field of a
domestic marine outfall located off the city of Rio de Janeiro was evaluated
through field work comprising fluorescent dye tracer injection and tracking with
simultaneous monitoring of sea water turbidity. A preliminary laboratory
assessment was carried out with a sample of the outfall effluent whose turbidity
was measured by the nephelometric method before and during a serial dilution
process. During the field campaign, the dye tracer was monitored with field
fluorometers and the turbidity was observed with an optical backscattering sensor
interfaced to an OEM data acquisition system. About 4,000 samples were gathered,
covering an area of 3 km * 3 km near the outfall diffusers. At the far field -
where a drift towards the coastline was observed - the effluent plume was
adequately labeled by the dye tracer. The turbidity plume was biased due to the
high and variable background turbidity of sea water. After processing the
turbidity dataset with a baseline detrending method, the plume presented high
correlation with the dye tracer plume drawn on the near dilution field. However,
dye tracer remains more robust than effluent turbidity.
PMID- 29339627
TI - Corrigendum: Water Science and Technology 76 (2), 323-336 Detoxification of photo
catalytically treated 2-chlorophenol: optimization through response surface
methodology, doi: 10.2166/wst.2017.152.
PMID- 29339629
TI - Utility of Routine Surveillance Imaging for Hodgkin Disease following Autologous
Transplant: Experiences from a Single Institution.
AB - BACKGROUND: Surveillance scans performed after autologous stem cell transplant
(auto-HCT) for patients with Hodgkin disease (HD) have no proven survival
benefit. METHODS: We studied survival differences among patients with HD after
auto-HCT whose recurrences were detected on clinical history and exam, versus
those detected on routine surveillance scan. RESULTS: Among the 98 patients with
HD that underwent auto-HCT from 2000 to 2014 at our institution, 30 relapsed, of
which 21 were detected radiologically and 9 clinically. There were no
statistically significant differences in patient characteristics between the 2
groups. The median time to progression was 118 days for the clinical cohort and
284 days for the radiological cohort (p = 0.05). Median overall survival (OS) was
728 days for the clinical cohort, and was not reached for the radiological cohort
(p = 0.02). DISCUSSION: In our review, most patients with HD after auto-HCT were
diagnosed radiologically. Patients whose relapse was diagnosed clinically were
likely to be detected earlier and have a shorter OS. Patients with aggressive
disease may be detected when clinically relevant, regardless of scanning. Routine
scanning may not be necessary in the majority of patients with HD following auto
HCT.
PMID- 29339628
TI - Downregulation of Long Non-Coding RNA Kcnq1ot1: An Important Mechanism of Arsenic
Trioxide-Induced Long QT Syndrome.
AB - BACKGROUND/AIMS: Arsenic trioxide (ATO) is a known anti-acute promyelocytic
leukemia (APL) reagent, whose clinical applications are limited by its serious
cardiac toxicity and fatal adverse effects, such as sudden cardiac death
resulting from long QT syndrome (LQTS). The mechanisms of cardiac arrhythmia due
to ATO exposure still need to be elucidated. Long non-coding RNAs (lncRNAs) are
emerging as major regulators of various pathophysiological processes. This study
aimed to explore the involvement of lncRNAs in ATO-induced LQTS in vivo and in
vitro. METHODS: For in vivo experiments, mice were administered ATO through the
tail vein. For in vitro experiments, ATO was added to the culture medium of
primary cultured neonatal mouse cardiomyocytes. To evaluate the effect of lncRNA
Kcnq1ot1, siRNA and lentivirus-shRNA were synthesized to knockdown lncRNA
Kcnq1ot1. RESULTS: After ATO treatment, the Kcnq1ot1 and Kcnq1 expression levels
were down regulated. lncRNA Kcnq1ot1 knockdown prolonged the action potential
duration (APD) in vitro and exerted LQTS in vivo. Correspondingly, Kcnq1
expression was decreased after silencing lncRNA Kcnq1ot1. However, the knockdown
of Kcnq1 exerted no effect on lncRNA Kcnq1ot1 expression. CONCLUSIONS: To our
knowledge, this report is the first to demonstrate that lncRNA Kcnq1ot1
downregulation is responsible for QT interval prolongation induced by ATO at
least partially by repressing Kcnq1 expression. lncRNA Kcnq1ot1 has important
pathophysiological functions in the heart and could become a novel antiarrhythmic
target.
PMID- 29339631
TI - Abstracts of Award-Winning Posters, 22nd Annual Health Sciences Poster
Conference, Faculty of Medicine, Health Sciences Centre, Kuwait University,
Kuwait, March 7-9, 2017: Abstracts.
PMID- 29339630
TI - Comparison of the Efficacy of Different Drugs on Non-Motor Symptoms of
Parkinson's Disease: a Network Meta-Analysis.
AB - BACKGROUND/AIMS: A network meta-analysis is used to compare the efficacy of
ropinirole, rasagiline, rotigotine, entacapone, apomorphine, pramipexole,
sumanirole, bromocriptine, piribedil and levodopa, with placebo as a control, for
non-motor symptoms in Parkinson's disease (PD). METHODS: PubMed, Embase and the
Cochrane Library were searched from their establishment dates up to January 2017
for randomized controlled trials (RCTs) investigating the efficacy of the above
ten drugs on the non-motor symptoms of PD. A network meta-analysis combined the
evidence from direct comparisons and indirect comparisons and evaluated the
pooled weighted mean difference (WMD) values and surfaces under the cumulative
ranking curves (SUCRA). The network meta-analysis included 21 RCTs. RESULTS: The
analysis results indicated that, using the United Parkinson's Disease Rating
Scale (UPDRS) III, the efficacies of placebo, ropinirole, rasagiline, rotigotine,
entacapone, pramipexole, sumanirole and levodopa in treating PD were lower than
that of apomorphine (WMD = -10.90, 95% CI = -16.12~-5.48; WMD = -11.85, 95% CI =
17.31~-6.16; WMD = -11.15, 95% CI = -16.64~-5.04; WMD = -11.70, 95% CI = -16.98~
5.60; WMD = -11.04, 95% CI = -16.97~-5.34; WMD = -13.27, 95% CI = -19.22~-7.40;
WMD = -10.25, 95% CI = -15.66~-4.32; and WMD = -11.60, 95% CI = -17.89~-5.57,
respectively). Treatment with ropinirole, rasagiline, rotigotine, entacapone,
pramipexole, sumanirole, bromocriptine, piribedil or levodopa, with placebo as a
control, on PD exhibited no significant differences on PD symptoms when the UPDRS
II was used for evaluation. Moreover, using the UPDRS III, the SUCRA values
indicated that a pomorphine had the best efficacy on the non-motor symptoms of PD
(99.0%). Using the UPDRS II, the SUCRA values for ropinirole, rasagiline,
rotigotine, entacapone, pramipexole, sumanirole, bromocriptine, piribedil and
levodopa treatments, with placebo as a control, indicated that bromocriptine
showed the best efficacy on the non-motor symptoms of PD (75.6%). CONCLUSION:
Among ropinirole, rasagiline, rotigotine, entacapone, apomorphine, pramipexole,
sumanirole, bromocriptine, piribedil and levodopa, with placebo as a control,
apomorphine may be the most efficacious drug for therapy in treating the non
motor symptoms of PD.
PMID- 29339632
TI - Identification of Rifampicin Resistance Mutations in Escherichia coli, Including
an Unusual Deletion Mutation.
AB - Rifampicin is an effective antibiotic against mycobacterial and other bacterial
infections, but resistance readily emerges in laboratory and clinical settings.
We screened Escherichia coli for rifampicin resistance and identified numerous
mutations to the gene encoding the beta-chain of RNA polymerase (rpoB), including
an unusual 9-nucleotide deletion mutation. Structural modeling of the deletion
mutant indicates locations of potential steric clashes with rifampicin. Sequence
conservation in the region near the deletion mutation suggests a similar mutation
may also confer resistance during the treatment of tuberculosis.
PMID- 29339634
TI - Abstracts of Theses Approved for MSc Degrees at the Faculty of Medicine, Health
Sciences Center, Kuwait University, Kuwait: Abstracts.
PMID- 29339633
TI - Multiple Sclerosis Mortality by Race/Ethnicity, Age, Sex, and Time Period in the
United States, 1999-2015.
AB - BACKGROUND: Multiple sclerosis (MS) carries high morbidity and shortens life
span. While there is recent recognition of other US minority populations such as
blacks and Hispanics being affected with MS, examination of MS-specific mortality
trends by race/ethnicity has been lacking. OBJECTIVE: To investigate MS mortality
rates and trends in the United States by sex, age, and race/ethnicity. METHODS:
We used the Compressed Mortality data file for 1999-2015 in the Wide-ranging
online Data for Epidemiological Research system developed by the Center for
Disease Control and Prevention to calculate the age-adjusted (US 2000 standard
population) and age-specific MS mortality rate (per 100,000) by race/ethnicity
and sex over time. Five mutually exclusive racial/ethnic groups were included in
the analysis: non-Hispanic (NH) white, NH black, NH Asian or Pacific Islander
(API), NH American Indian or Alaska Native, and Hispanic. RESULTS: The average
annual age-adjusted MS mortality rate was highest among NH whites (0.90 for males
and 1.50 for females) immediately followed by NH blacks (0.75 for males and 1.42
for females), and lowest among APIs (0.05 for males and 0.12 for females).
Statistically significant, increasing trend in age-adjusted MS mortality was
observed during 1999-2015 among NH whites and NH blacks regardless of sex, more
substantially in the latter. Age-specific MS mortality patterns showed NH blacks
had the highest rate under age 55 and NH whites had the highest rate after that
age point. For these 2 groups, MS mortality increased with age in both sexes and
peaked at ages 55-64 for NH blacks and 65-74 for NH whites before declining
substantially, while for Hispanic and API groups the risk plateaued after age 55.
CONCLUSION: MS-specific mortality trends demonstrate distinctive differences by
race/ethnicity and age. The observations that whites and females are more likely
to die from MS is in line with the overall understanding that these groups are
affected more by MS. However, the findings of blacks dying at an earlier age and
having more substantially increasing mortality trends than whites suggest that MS
burden weighs unequally by race. Further investigation into these trends may
provide additional evidence into risk or protective factors within each group.
PMID- 29339635
TI - Response to the Letter to the Editor Regarding "Micronutrients, Essential Fatty
Acids and Bone Health in Phenylketonuria".
PMID- 29339636
TI - Successful Treatment of Autoimmune Urticaria with Low-Dose Prednisolone Therapy
Administered for a Few Months: A Case Series of 42 Patients.
AB - BACKGROUND: Chronic spontaneous urticaria (CSU) is defined as symptoms of
urticaria persisting for 6 weeks or more without obvious cause. Autologous serum
skin test (ASST) positivity in patients with CSU is considered to be associated
with autoimmune urticaria (AIU). METHODS: In this retrospective study we
retrieved the medical records of 1,073 urticaria patients seen at the Department
of Dermatology and Allergology of Szeged University between January 2005 and
February 2014. Forty-two patients (36 female and 6 male) met the study criteria
by having CSU and giving positive results in the ASST. Our aim was to assess the
clinical efficacy and safety of low-dose oral prednisolone therapy administered
to patients with antihistamine-refractory ASST-positive CSU for a few months.
Patients were given an initial dose (40 mg/day) of prednisolone until the
complete resolution of the symptoms, usually 7-10 days, and then the dose was
gradually decreased, as in other autoimmune diseases. RESULTS: Prednisolone
therapy lasted for an average of 3.6 months and a complete long-lasting response
was achieved in 35 of 42 AIU patients (83.3%). The follow-up period was at least
36 months (3 years) for each AIU patient; the longest follow-up time was 139
months (11.5 years). None of the patients reported any considerable side effects.
CONCLUSION: Based on our results, we suggest that the use of this treatment could
be an alternative for the treatment of AIU. Our present results also highlight
the need for other therapies in a small percentage of AIU patients. Our results
suggest that AIU represents a transient autoimmunity that can be successfully
treated with low-dose steroid therapy administered for a few months.
PMID- 29339637
TI - Corneal Collagen Crosslinking Combined with Phototherapeutic Keratectomy and
Photorefractive Keratectomy for Corneal Ectasia after Laser in situ
Keratomileusis.
AB - PURPOSE: The aim of this study was to analyze the effects of corneal crosslinking
(CXL) combined with phototherapeutic keratectomy (PTK) and photorefractive
keratectomy (PRK) in halting the progression and improving the visual function of
corneal ectasia after laser in situ keratomileusis (LASIK). METHODS: PTK-PRK-CXL
was performed on 14 eyes of 14 patients who developed corneal ectasia after
LASIK. The visual acuity, spherical refraction and cylinder, corneal topography
indices, thinnest corneal thickness (TCT), and endothelial cell count were
evaluated at baseline and at 1, 3, 6, and 12 months postoperatively. RESULTS: The
mean uncorrected visual acuity improved significantly from 0.64 +/- 0.36 logMAR
preoperatively to 0.19 +/- 0.12 logMAR at 12 months of follow-up (p < 0.001),
while the mean best corrected visual acuity improved from 0.21 +/- 0.14 logMAR at
baseline to 0.04 +/- 0.10 logMAR at 12 months postoperatively (p < 0.001). A
significant decrease was observed in Kmax and Kmean values from 52.51 +/- 6.74
and 43.55 +/- 3.37 D at baseline to 45.72 +/- 5.18 (p < 0.001) and 40.60 +/- 3.05
D (p < 0.001) at the 1-year follow-up. The mean TCT decreased significantly from
419.07 +/- 36.56 um before treatment to 320.93 +/- 39.78 um at 12 months of
follow-up (p < 0.001), and there was no significant endothelial cell loss (p >
0.05) beyond 6 months after treatment. CONCLUSION: PTK-PRK-CXL is a promising
procedure to halt the progression of post-LASIK keratectasia with significant
visual quality improvement.
PMID- 29339638
TI - A Nomogram to Characterize the Severity of Detrusor Overactivity during the Ice
Water Test: Description of the Method and Proof of Concept.
AB - AIMS: To develop a nomogram with severity categories for detrusor overactivity
(DO). METHODS: By conducting ice water tests (IWT) in 55 patients with
Parkinson's disease, we identified criteria to describe characteristics of the
detrusor pressure curves: (1) a gradient of Deltapdet over Deltat at the maximum
detrusor pressure and (2) the area under the curve. In a nomogram, 10 severity
categories of DO were established: 1 and 2 were assigned to group A (mild), 3 and
4 to group B (moderate) and 5-10 to group C (severe). RESULTS: In the nomogram,
negative IWT (20) appeared in category 1. Positive IWT (35) spread over the
categories 1-8, 17 in group A, 11 in group B and 7 in categories 5-10. A
relationship of incontinence episodes and nomogram category was observed. The
nomogram category was reproducible in repeated IWT. Therapeutic interventions to
treat DO lowered the nomogram category. CONCLUSION: From the relationship of
detrusor pressure and time in the IWT, a nomogram with 10 severity categories of
DO was developed. First observations show a relationship of nomogram category and
the number of incontinence episodes, reproducibility in repeated tests and the
representation of effects of therapeutic interventions to treat DO.
PMID- 29339639
TI - MRI-Guided Interstitial Laser Ablation for Intracranial Lesions: A Large Single
Institution Experience of 133 Cases.
AB - BACKGROUND: Managing difficult-to-access lesions or surgically accessible lesions
in fragile patients is a central problem in neurosurgery. MRI-guided interstitial
laser ablation (ILA) is a minimally invasive option that may provide a safe means
of treating these challenging patients. OBJECTIVE: We aim to (1) evaluate safety,
efficacy, and preliminary outcomes within a diverse and large series of ILA
treatments; and (2) report technical details and operative trends that proved
useful over time in the authors' experience and that may be of use to
neurosurgeons who perform ILA. METHODS: A retrospective evaluation of ILA
patients was performed in terms of demographics, surgical techniques, and
clinical outcomes. RESULTS: A total of 133 intracranial lesions in 120 patients
were treated with ILA, including glioblastomas (GBM), other gliomas, metastases,
epilepsy foci, and radionecrosis. The rate of complications/unexpected
readmission was 6.0%, and the mortality rate was 2.2%. With high-grade tumors,
tumor volumes >3 cm in diameter trended toward a higher rate of complication (p =
0.056). Median progression-free survival (PFS) and overall survival (OS) for
recurrent GBM were 7.4 and 11.6 months, respectively. As a frontline treatment
for newly diagnosed GBM, median PFS and OS were 5.9 and 11.4 months,
respectively. For metastases, median PFS was not yet reached, and OS was 17.2
months. CONCLUSION: Our series suggests that ILA is a safe and efficacious
treatment for a variety of intracranial pathologies, can be tailored to treat
difficult-to-access lesions, and may offer a novel alternative to open craniotomy
in properly selected patients.
PMID- 29339640
TI - Application of Immunocytochemistry on Cell Block Sections for the Investigation
of Thyroid Lesions.
AB - OBJECTIVE: To investigate the potential of Classification and Regression Trees
(CARTs) for the diagnosis of thyroid lesions based on cell block
immunocytochemistry and cytological outcome. STUDY DESIGN: A total of 956
histologically confirmed cases (673 benign and 283 malignant) from patients with
thyroid nodules were prepared via liquid-based cytology and evaluated; 4
additional slides were stained for cytokeratin 19 (CK-19), galectin 3 (Gal-3),
Hector Battifora mesothelial cell 1 (HBME-1), and thyroglobulin. On the basis of
immunocytochemistry and the cytological diagnosis, a CART algorithm was
constructed and used for evaluation. RESULTS: The major important factors
contributing to the diagnostic CART model were: cytological outcome, CK-19, Gal
3, and HBME-1. The sensitivity and specificity of the cytological diagnosis were
96.27% and 88.26%, respectively (cut-off: category 3 of The Bethesda System [TBS
3]). The introduction of immunocytochemistry and the CART model increased the
sensitivity and specificity to 98.88% and 99.11%, respectively. CK-19 presented
the best performance for discriminating papillary thyroid carcinomas, followed by
HBME-1 and Gal-3. In the TBS-2 cases, CK-19 and, subsequently, Gal-3 were
important immunocytochemistry markers. Ultimately, CK-19 and HBME-1 on TBS-5 or
TBS-6 cases demonstrated the best results. CONCLUSIONS: The hierarchical
structure of the CART model provides a diagnostic algorithm linked with the risk
of malignancy at every step of the procedure. It also provides guidance on the
use of ancillary examinations as it goes by simple, human understandable rules.
PMID- 29339641
TI - Longitudinal Assessment of Abdominal Circumference versus Estimated Fetal Weight
in the Detection of Late Fetal Growth Restriction.
AB - OBJECTIVES: To perform a longitudinal assessment comparison between estimated
fetal weight (EFW) and abdominal circumference (AC) in the prediction of late
fetal growth restriction (FGR) as opposed to small for gestational age (SGA).
PATIENTS AND METHODS: A cohort of unselected singleton pregnancies scanned at
32+/-2 and 37+/-1 weeks was created. Longitudinal growth assessment by
calculating the conditional AC and conditional EFW was performed, and both
parameters were compared for their prediction capacity for late FGR and SGA.
Conditional standards set an expected size (EFW or AC) given a first measurement
performed earlier. A declining growth was defined as a conditional growth of
<10th centile. RESULTS: A total of 938 pregnancies were included. As expected,
declining growth between 32+/-2 and 37+/-1 weeks was associated with late FGR and
SGA, but the predictive capacity of both conditional AC and conditional EFW was
comparably poor, with detection rates of 28% at a 10% rate of false positives for
late FGR. CONCLUSIONS: Longitudinal assessment of fetal growth during the third
trimester has a low predictive capacity for late FGR, with no differences between
conditional AC and conditional EFW.
PMID- 29339642
TI - Significance of Salvage Autologous Stem Cell Transplantation for Relapsed
Multiple Myeloma: A Nationwide Retrospective Study in Japan.
AB - Autologous stem cell transplantation (ASCT) has been employed for patients with
relapsed multiple myeloma (MM) after up-front ASCT. The present retrospective
study aimed to examine the survival benefit from salvage ASCT. Among 446 patients
with relapsed MM after up-front single ASCT, 70 patients received salvage ASCT,
the employment of which reduced the risk of mortality after relapse (p = 0.041).
Using the parameters before initial ASCT, the advantage of salvage ASCT compared
to standard therapy was confirmed in the subgroup with an international staging
system stage of I or II (p = 0.040), good performance status (PS; p = 0.043), or
no/mild renal comorbidity (p = 0.029). The advantage of salvage ASCT was also
confirmed in the subgroup excluding those with early relapse within 7 months
after initial ASCT (p = 0.026). Among patients who received salvage ASCT, a
favorable prognosis is apparent for those with a time to relapse after initial
ASCT of longer than 24 months. The overall survival after salvage ASCT was
favorable excluding patients with the following factors: early relapse, poor PS,
moderate/severe renal comorbidity, and progressive disease (p < 0.001). In
conclusion, our results reinforced the evidence for encouraging salvage ASCT for
eligible patients.
PMID- 29339643
TI - Effect of Remote Ischemic Preconditioning on Systemic Toxicity and Ototoxicity
Induced by Cisplatin in Rats: Role of TNF-alpha and Nitric Oxide.
AB - BACKGROUND/AIMS: Cisplatin is a chemotherapeutic agent. The use of remote
ischemic preconditioning (RIPC) was proposed after the observation that ischemic
preconditioning of a cardiac vascular area could protect another completely
distinctly. METHODS: This is an experimental study. Male Wistar rats were
anesthetized, and they underwent a hearing evaluation via measurement of the
brainstem auditory evoked potential (BSAEP). Then, cisplatin was administered
intraperitoneally (IP) at a dose of 8 mg/kg/day for 4 consecutive days to group
1, whereas saline solution was administered IP to group 2. In groups 3 and 4,
ischemia of the right hind paw was performed for 10 min, followed by reperfusion
for 30 min, after which cisplatin or saline was administered IP to group 3 or
group 4, respectively. Afterwards, all animals were evaluated via the BSAEP. The
right cochlea was dissected for immunohistochemistry. RESULTS: RIPC lowered the
increase in BSAEP of the animals treated with cisplatin (p = 0.0146). Weight loss
decreased in the animals subjected to RIPC (p < 0.005). In group 3, RIPC reversed
immunostaining for tumor necrosis factor-alpha and inducible nitric oxide
synthase in the stria vascularis injured by cisplatin (p < 0.05). CONCLUSION:
RIPC protects against systemic toxicity and ototoxicity induced by cisplatin in
rats.
PMID- 29339644
TI - Changes in Central Macular Thickness and Retinal Nerve Fiber Layer Thickness in
Eyes with Vogt-Koyanagi-Harada Disease: A 2-Year Follow-Up Study.
AB - PURPOSE: To investigate the central macular thickness (CMT) and retinal nerve
fiber layer (RNFL) thickness in eyes with Vogt-Koyanagi-Harada (VKH) disease
associated with optic disc swelling and serous retinal detachment through a 24
month follow-up period. METHODS: We prospectively investigated 28 eyes of 14
treatment-naive patients with acute VKH disease associated with optic disc
swelling and serous retinal detachment and 30 eyes of 15 normal individuals to
compare changes in the CMT and average RNFL thickness. RESULTS: The CMT was
significantly lower in the eyes of the VKH group at 12 and 24 months. The RNFL
thickness was significantly higher in the eyes of the VKH group at the initial
visit and at the 6- and 12-month follow-up visits, but no significant difference
was found between the VKH group and control group at the 24-month follow-up
visit. CONCLUSION: Significant changes in the CMT and RNFL thickness in the eyes
with VKH disease were observed during the 24-month follow-up period. When
diagnosing or monitoring diseases including glaucoma and neuro-ophthalmic
diseases that affect the retinal thickness in patients with VKH disease, we
recommend considering longitudinal changes in the retinal thickness.
PMID- 29339645
TI - Multi Matrix System Mesalazine Plus Rectal Mesalazine in the Treatment of Mild to
Moderately Active Ulcerative Proctitis.
AB - BACKGROUND: Mesalazine 1 g suppository/die is used for mild to moderately active
ulcerative proctitis (UP). Whether addiction of Multi Matrix System (MMX)
mesalazine increases the remission rate of UP and prevents proximal extension of
disease is unknown. METHODS: This is a retrospective study on 116 outpatients
with UP who had been treated with one of the following regimens: (1) MMX
mesalazine 1.2 g/die plus mesalazine suppositories for 8 +/- 2 weeks and,
subsequently, MMX mesalazine 1.2 g/die plus rectal mesalazine 1 g every other day
for at least 6 months; (2) mesalazine 1 g suppositories/die alone for 8 +/- 2
weeks and, subsequently, rectal mesalazine 1 g every other day for 6 more months.
Patients were evaluated clinically at 2 months (+/-2 weeks) and endoscopically at
6 months (+/-2 weeks). For categorical variables, Pearson chi-square test was
used. RESULTS: A total of 46 of 55 patients (84%) on combined therapy and 49 of
61 patients (80%) on rectal mesalazine reached clinical remission (p > 0.05; OR
0.79, 95% CI 0.30-2.07). At 6 months follow-up, proximal extension of disease was
observed in 7 of 55 (14%) patients on combined therapy and in 18 of 61 (29%)
patients on rectal mesalazine alone (p < 0.05; OR 2.87, 95% CI 1.09-7.53).
CONCLUSIONS: Oral MMX mesalazine plus rectal mesalazine combined treatment is
associated with prevention of proximal extension of the disease compared with
rectal mesalazine alone.
PMID- 29339646
TI - Automated Screening for Diabetic Retinopathy - A Systematic Review.
AB - PURPOSE: Worldwide ophthalmologists are challenged by the rapid rise in the
prevalence of diabetes. Diabetic retinopathy (DR) is the most common complication
in diabetes, and possible consequences range from mild visual impairment to
blindness. Repetitive screening for DR is cost-effective, but it is also a costly
and strenuous affair. Several studies have examined the application of automated
image analysis to solve this problem. Large populations are needed to assess the
efficacy of such programs, and a standardized and rigorous methodology is
important to give an indication of system performance in actual clinical
settings. METHODS: In a systematic review, we aimed to identify studies with
methodology and design that are similar or replicate actual screening scenarios.
A total of 1,231 publications were identified through PubMed, Cochrane Library,
and Embase searches. Three manual search strategies were carried out to identify
publications missed in the primary search. Four levels of screening identified 7
studies applicable for inclusion. RESULTS: Seven studies were included. The
detection of DR had high sensitivities (87.0-95.2%) but lower specificities (49.6
68.8%). False-negative results were related to mild DR with a low risk of
progression within 1 year. Several studies reported missed cases of diabetic
macular edema. A meta-analysis was not conducted as studies were not suitable for
direct comparison or statistical analysis. CONCLUSION: The study demonstrates
that despite limited specificity, automated retinal image analysis may
potentially be valuable in different DR screening scenarios with a relatively
high sensitivity and a substantial workload reduction.
PMID- 29339647
TI - Proceedings of the 11th Congress of the International Society of Nutrigenetics
and Nutrigenomics (ISNN 2017).
AB - The International Society of Nutrigenetics and Nutrigenomics (ISNN) held its 11th
annual Congress in Los Angeles, California, between September 16 and 19, 2017. In
addition to 2 keynote lectures, 4 plenary sessions included presentations by
internationally renowned speakers on cutting-edge areas of research and new
discoveries in genetics/genomics, the microbiome, and nutrition. Scientific
topics included multi-omics approaches; diet and the microbiome; cancer,
longevity, and metabolism; moving the field forward; and
translational/educational aspects and the future of medicine. There was also an
accepted oral abstracts session designed specifically to provide young
investigators and trainees with the opportunity to present their work, as well as
a session focused on industry-academic partnerships, which included a roundtable
discussion afterwards. Overall, the 11th ISNN Congress was an exciting and
intellectually stimulating meeting focused on understanding the impact of
biological interactions between genes and nutrients on health and disease. These
efforts continued the decade-long tradition of the annual ISNN Congress to
provide an interdisciplinary platform for scientists from various disciplines to
discuss research ideas and advance the fields of nutrigenetics and nutrigenomics.
PMID- 29339648
TI - Caries-Preventive Effect of NaF, NaF plus TCP, NaF plus CPP-ACP, and SDF
Varnishes on Sound Dentin and Artificial Dentin Caries in vitro.
AB - The aim of this study was to compare the caries-preventive effect of different
fluoride varnishes on sound dentin as well as on artificial dentin caries-like
lesions. Bovine dentin specimens (n = 220) with one sound surface (ST) and one
artificial caries lesion (DT) were prepared and randomly allocated to 11 groups.
The interventions before pH cycling were as follows: application of a varnish
containing NaF (22,600 ppm F-; Duraphat [NaF0/NaF1]), NaF plus tricalcium
phosphate (22,600 ppm F-; Clinpro White Varnish Mint [TCP0/TCP1]), NaF plus
casein phosphopeptide-stabilized amorphous calcium phosphate complexes (CPP-ACP;
22,600 ppm F-; MI Varnish [CPP0/CPP1]), or silver diamine fluoride (SDF; 35,400
ppm F-; Cariestop 30% [SDF0/SDF1]) and no intervention (NNB/N0/N1). During pH
cycling (14 days, 6 * 120 min demineralization/day) half of the specimens in each
group were brushed (10 s; 2 times/day) with either fluoride-free ("0"; e.g.,
TCP0) or 1,100 ppm F- ("1"; e.g., TCP1) dentifrice slurry. In another subgroup,
the specimens were pH cycled but not brushed (NNB). Differences in integrated
mineral loss (DeltaDeltaZ), lesion depth (DeltaLD), and colorimetric values
(DeltaDeltaE) were calculated between the values after initial demineralization
and those after pH cycling, using transversal microradiography and photographic
images. After pH cycling, no discoloration could be observed. Furthermore, NNB,
N0, and N1 showed significantly increased DeltaZDT/LDDT and DeltaZST/LDST values,
indicating further demineralization. In contrast, CPP0, CPP1, SDF0, and SDF1
showed significantly decreased DeltaZDT/LDDT values, indicating remineralization
(p <= 0.004; paired t test). CPP0, CPP1, SDF0, and SDF1 showed significantly
higher changes in DeltaDeltaZDT/DeltaLDDT and DeltaDeltaZST/DeltaLDST than NNB,
N0, and N1 (p < 0.001; Bonferroni post hoc test). In conclusion, under the
conditions chosen, all fluoride varnishes prevented further demineralization.
However, only NaF plus CPP-ACP and SDF could remineralize artificial dentin
caries-like lesions under net-demineralizing conditions, thereby indicating that
NaF plus CPP-ACP and SDF may be helpful to high-caries-risk patients.
PMID- 29339649
TI - Cardiovascular Risk Factors and Insulin Resistance after Two Hypocaloric Diets
with Different Fat Distribution in Obese Subjects: Effect of the rs10767664 Gene
Variant in Brain-Derived Neurotrophic Factor.
AB - BACKGROUND: The role of brain-derived neurotrophic factor (BDNF) variants on
change in body weight and cardiovascular risk factors after weight loss remains
unclear in obese patients. OBJECTIVE: Our aim was to analyze the effects of the
rs10767664 BDNF gene polymorphism on body weight, cardiovascular risk factors,
and serum adipokine levels after a high monounsaturated fatty acids (MUFAs)
hypocaloric diet (diet M) versus a high polyunsaturated fatty acids (PUFAs)
hypocaloric diet (diet P). METHODS: A Caucasian population of 361 obese patients
was enrolled. Subjects who met the inclusion criteria were randomly allocated to
one of two diets for a period of 3 months. RESULTS: Two hundred and sixteen
subjects (59.8%) had the genotype AA (wild-type group), and 145 (40.2%) patients
had the genotypes AT (122 patients, 33.8%) or TT (23 patients, 6.4%) (mutant-type
group). After weight loss with diet P and diet M and in both genotype groups,
body mass index, weight, fat mass, waist circumference, systolic blood pressure,
serum leptin levels, low-density lipoprotein cholesterol, and total cholesterol
decreased in a significant way. Secondary to weight loss with diet M and only in
the wild-type group, insulin levels (-2.1 +/- 2.0 vs. -0.7 +/- 2.9 IU/L, p <
0.05) and homeostatic model assessment of insulin resistance (-0.7 +/- 0.9 vs.
0.3 +/- 1.0 U, p < 0.05) decreased. CONCLUSION: Our data show that the rs10767664
variant of the BDNF gene modifies insulin resistance and insulin levels after
weight loss with a hypocaloric diet enriched with MUFAs.
PMID- 29339650
TI - Oral Immunotherapy in Japanese Children with Anaphylactic Peanut Allergy.
AB - BACKGROUND: Reports on oral immunotherapy (OIT) for anaphylactic food allergy are
lacking. We investigated the efficacy and safety of peanut OIT for anaphylactic
patients. METHODS: We enrolled 22 peanut anaphylactic patients who underwent OIT
between 2011 and 2013, all of whom demonstrated anaphylaxis during a baseline
double-blind, placebo-controlled food challenge. After starting in-hospital OIT,
participants gradually increased ingestion to 795 mg of peanut protein per day at
home and then took a maintenance dose (795 mg) daily. After 3 asymptomatic
months, participants underwent an oral food challenge (OFC) of 795 mg after 2
weeks of peanut avoidance to confirm sustained unresponsiveness. The historical
control group consisted of 11 patients with anaphylaxis by OFC and underwent the
second OFC after 2 years. RESULTS: All patients (22/22) achieved desensitization
by 8 months after starting OIT and completed the protocol within 2 years. Two
years later, 15/22 patients (68.1%) in the OIT group achieved sustained
unresponsiveness, whereas only 2 (18.1%) in the control group passed the second
OFC. After 2 years, the median peanut-specific IgE had significantly decreased
(from 38.5 to 12.4 kUA/L) in the OIT group, but not in the control group. Median
peanut- and Ara h 2-specific IgG4 in the OIT group had significantly increased
from baseline after 1 month. The adverse reaction rate per ingestion was 43% in
hospital and 5% at home. Three patients received adrenaline at the hospital and 2
at home. CONCLUSIONS: These data suggest that for patients with peanut
anaphylaxis, OIT can increase the threshold and support achieving sustained
unresponsiveness with relative safety.
PMID- 29339651
TI - Albumin-Indocyanine Green Evaluation Grading System Predicts Post-Hepatectomy
Liver Failure for Biliary Tract Cancer.
AB - BACKGROUND: In biliary tract cancer treatment, a precise preoperative evaluation
of the patient's liver function is essential to avoid post-hepatectomy liver
failure (PHLF) and mortality. The present study aimed to evaluate the role of the
Albumin-Indocyanine Green Evaluation (ALICE) grading system in predicting PHLF in
biliary tract cancer patients. METHODS: Data from 166 patients who underwent
hepatectomy for biliary tract cancer between 2000 and 2016 were retrospectively
analyzed. Univariate and multivariate analyses were performed to identify the
risk factors for PHLF. RESULTS: Among the 166 patients, major hepatectomy was
performed in 101 (61%) and bile duct resection was performed in 99 (60%)
patients. Thirteen (8%) patients developed PHLF. Furthermore, PHLF, major
complications, and mortality were significantly higher in patients with high
ALICE grades (>=2b) than in those with low ALICE grades (<2b) (PHLF, 42 vs. 18%,
p = 0.002; major complications, 35 vs. 19%, p = 0.036; mortality, 9.3 vs. 0%, p =
0.001). In multivariate analysis, high ALICE grade (p = 0.016) and blood loss
>=1,500 mL (p = 0.009) were identified as independent risk factors for PHLF.
CONCLUSIONS: The ALICE grading system effectively stratified the risks for PHLF
for biliary tract cancer.
PMID- 29339652
TI - Smoking and Promoter-Specific Deoxyribonucleic Acid Methylation of the Atrial
Natriuretic Peptide Gene: Methylation of Smokers and Non-Smokers Differs
Significantly during Withdrawal.
AB - BACKGROUND: Atrial natriuretic peptide (ANP) is well known in psychiatric
disorders to modulate hypothalamic-pituitary-adrenal axis activity. Disturbances
of ANP have been described in early abstinent alcohol-dependent patients. This is
the first longitudinal investigation on cytosine-phosphatidyl-guanine (CpG)
island promoter methylation of the ANP gene in the blood of tobacco-dependent
patients. METHODS: In a longitudinal approach, we investigated whether changes in
ANP serum levels correlated to CpG methylation of the respective gene promoters
on days 1, 7, and 14 of tobacco withdrawal. RESULTS AND CONCLUSION: Compared to
non-smokers, promoter-related deoxyribonucleic acid methylation of the ANP
promoter was significantly elevated on days 7 and 14 of withdrawal in tobacco
dependent patients. Baseline methylation status of the ANP promoter was not
significantly different from controls, arguing for an impaired regulation during
withdrawal.
PMID- 29339653
TI - Adherence to the European Association of Urology Guidelines: A National Survey
among Italian Urologists.
AB - OBJECTIVE: The study aimed to explore adherence to the European Urological
Association (EAU) Guidelines (GLs) grade A recommendation among Italian
urologists. MATERIALS AND METHODS: A 13-item multiple-choice questionnaire
covering oncological and non-oncological urological diseases was e-mailed to all
Italian Urologist Society (Societa Italiana di Urologia or SIU) members. We asked
members to provide an explanation for their answer choice where needed. The
quantitative data were tested using the Pearson's chi-square test. For all
statistical comparisons, significance was considered as p < 0.05. RESULTS: Of the
2011 invited SIU members, 210 (10.4%) completed the survey. The sample was
composed of 22 (10.5%) Academic Urologists (AcUs), 110 (52.4%) Attending
Urologists (AtUs), 32 (15.2%) Private Practice Urologists (PPUs), and 41 (19.5%)
Residents in Urology (RUs). The mean adherence to the EAU Oncologic GLs ranged
from 54.5 to 97.1%, while the adherence to the non-oncologic GLs ranged from 45
to 87.6%. We found that adherence differed across the working categories
assessed. CONCLUSION: Our survey showed that professional role, updates, and
local facilities seem to be the drivers that influence the non-adherence to the
GLs. Urologists who work in university hospital would be more inclined to adopt
the GLs compared to those who practice in non-academic centers.
PMID- 29339654
TI - Comparative Burden of Subclinical Tremor in a Cohort of Normal Individuals
Stratified by Familial Risk for Essential Tremor.
AB - BACKGROUND: The burden of mild (i.e., subclinical) tremor within essential tremor
(ET) families is not fully understood. We assessed the burden of mild tremor in a
cohort of 287 adults, none of whom reported tremor or were diagnosed with ET.
METHODS: We recruited adults in 2 groups based on the familial risk for ET: 244
high-risk individuals (i.e., reporting one or more first-degree relative with ET)
and 43 low-risk individuals (i.e., reporting no relatives with ET). Tremor was
objectively assessed on 4 hand-drawn spirals (total spiral score = 0-12). Mild
tremor was defined using 3 different cut points. RESULTS: The prevalence rates of
mild tremor among high-risk individuals ranged from 41.4 to 98.4% and were highly
dependent on the cut point. Above a certain threshold (i.e., a total spiral score
>=5), 1-in-5 (i.e., 19.7%) high-risk individuals exhibited mild tremor, whereas
no low-risk individuals did. High-risk individuals were 3.09-4.50 times more
likely than low-risk individuals to exhibit mild tremor. CONCLUSION: The burden
of ET extends beyond the boundaries of the clinically defined disease, and
partially expressed forms of ET are abundant in ET families. This fact greatly
complicates gene-finding studies and epidemiological studies whose goal is to
detect disease-linked associations.
PMID- 29339655
TI - The Impact of Arterial Clamping Technique in Robot-Assisted Partial Nephrectomy
on Renal Function and Surgical Outcomes: Six-Year Experience at Siriraj Hospital,
Thailand.
AB - INTRODUCTION: Robot-assisted partial nephrectomy (RAPN) with different arterial
clamping techniques has increasingly been performed to avoid ischemic injury to
nephron. However, postoperative renal function remains controversial. We
determine the impact of each renal arterial clamping on surgical and renal
outcomes after RAPN. MATERIALS AND METHODS: Patients who underwent RAPN at
Siriraj Hospital from 2010 to 2016 were retrospectively reviewed and stratified
into 3 cohorts: main-clamp (MAC), selective-clamp, and off-clamp. RESULTS: Main,
selective, and off-clamping were performed in 27, 38, and 12, respectively.
Median tumor size and Radius, Exophytic or endophytic, Nearness to collecting
system or sinus, Anterior or posterior, and Location relative to polar lines
(RENAL) score were 3 cm and 7, respectively. Longer operative time was observed
in MAC (p = 0.002) although estimated blood loss, transfusion rate, and
complication were comparable. Warm ischemia time was not different between
cohorts. However, number of patients with prolonged ischemia time in MAC were
greater (p <= 0.01). All margins were negative. Median postoperative and latest
glomerular filtration rate reduction were 3.8 and 5.3 mL/min/1.73 m2,
respectively without significant difference between cohorts. On multivariable
analysis, hypertension independently associated with reduced renal function
preserved (p = 0.03). Median follow-up was 18 months. CONCLUSIONS: Our study is
the first to report surgical and renal functional outcomes after RAPN in
Southeast-Asian population. Based on our experience, clamping techniques does not
impact on renal functions and complication rate was low even in small-volume
center.
PMID- 29339656
TI - New: The European Addiction Research Award.
PMID- 29339657
TI - The Practical Management of Chronic Pancreatitis: A Multidisciplinary Symposium
Held at the Annual Meeting of the Pancreatic Society of Great Britain and
Ireland, Manchester 2016.
AB - AIM: This study is about a questionnaire survey of delegates attending the
chronic pancreatitis symposium at the 2016 meeting of the Pancreatic Society of
Great Britain and Ireland and seeks a multidisciplinary "snapshot" overview of
practice. METHODS: A questionnaire was developed with multidisciplinary input.
Questions on access to specialist care, methods of diagnosis and treatment
including specific scenarios were incorporated. Eighty-three (66%) of 125
delegates effectively participated in this survey. RESULTS: Twenty-four (29%) had
neither a chronic pancreatitis MDT in their hospital nor a chronic pancreatitis
referral MDT. Most frequently utilised diagnostic modalities were CT, MR and EUS
with no respondents utilising duodenal intubation tests. Initial treatment was
provided through non-opiate analgesia by 69 (93%), through the use of opiates by
56 (76%) and through the use of co-analgesics by 49 (66%). Fifty two (68%)
routinely referred patients with alcohol-related disease for counselling.
Preferred treatment for large duct disease without mass was endoscopic therapy.
In older patients with a mass, pancreaticoduodenectomy was preferred. CONCLUSION:
This is a small study likely to be skewed by sampling bias but is thought to be
the first multidisciplinary survey of the management of chronic pancreatitis in
the United Kingdom and Ireland. The results show a need for comprehensive access
to specialist pancreatitis MDT care and there remains substantial variation in
management.
PMID- 29339658
TI - Survey Results of the Expert Meeting on Laparoscopic Surgery for Gallbladder
Cancer and a Review of Relevant Literature.
AB - BACKGROUND: Favorable outcomes of laparoscopic surgery for gallbladder cancer
(GBC) have been reported; yet consensus on the indications and surgical
techniques for laparoscopic surgery for GBC is lacking. OBJECTIVE: To evaluate
the current status of laparoscopic surgery for GBC by analyzing the results of a
survey of experts and by reviewing the relevant published literature. METHODS:
Before an expert meeting was held on September 10, 2016 in Seoul, Korea, an
international survey was undertaken of expert surgeons in the field of GBC
surgery. RESULTS: The majority of surgeons who responded agreed that laparoscopic
surgery has an acceptable role for suspicious or early GBC, and that laparoscopic
extended cholecystectomy has a value comparable to that of open surgery in
selected patients with GBC. However, the selection criteria for laparoscopic
surgery for overt GBC and the details of the surgical techniques varied among
surgeons. CONCLUSIONS: This survey and literature review revealed that
laparoscopic surgery for GBC is performed in highly selected cases. However, the
favorable outcomes in the published reports and the positive view of experienced
surgeons for this operative procedure suggest a high likelihood that laparoscopic
surgery will be more frequently performed for GBC in the future.
PMID- 29339659
TI - FcgammaR/ROS/CK2alpha Is the Key Inducer of NF-kappaB Activation in a Murine
Model of Asthma.
AB - BACKGROUND: The transcription factor nuclear factor (NF)-kappaB plays a pivotal
role in the development of allergic airway inflammation. However, the mechanism
of NF-kappaB activation in asthma remains to be elucidated. METHODS: CK2alpha
activation was assessed by CK2alpha phosphorylation and protein expression.
Airway levels of histamine and cytokines were determined by ELISA. We used 2
(active and passive) forms of allergic pulmonary inflammation models. In the
active form, the animals were immunized with ovalbumin (OVA) intraperitoneally,
followed by an airway challenge with OVA. In the passive form, the animals were
passively sensitized by intratracheal instillation with either anti-OVA IgE or
anti-OVA IgG, followed by an airway challenge with OVA. The role of NADPH oxidase
(NOX) in CK2alpha activation was assessed using NOX2-/- and NOX4-/- mice because
NOX2 and NOX4 contribute to many inflammatory diseases. RESULTS: The second
airway challenge increased CK2alpha phosphorylation and protein expression in
airway epithelial cells as well as nuclear translocation of the p50 and p65
subunits of NF-kappaB, all of which were inhibited by the CK2alpha inhibitor
4,5,6,7-tetrabromobenzotriazole and the antioxidant N-acetyl-L-cysteine. CK2alpha
phosphorylation and protein expression were significantly impaired in NOX2-/-,
but not in NOX4-/-, mice. Induction of passive sensitization using anti-OVA IgE
activated neither CK2alpha nor NF-kappaB. In contrast, induction of passive
sensitization using anti-OVA IgG activated both CK2alpha and NF-kappaB.
CONCLUSIONS: These data suggest that Fcgamma receptor/reactive oxygen
species/CK2alpha is a key inducer of NF-kappaB activation in airway epithelial
cells in a murine model of asthma.
PMID- 29339660
TI - Laparoscopic Surgery for Gallbladder Cancer: An Expert Consensus Statement.
AB - BACKGROUND: Despite the increasing number of reports on the favorable outcomes of
laparoscopic surgery for gallbladder cancer (GBC), there is no consensus
regarding this surgical procedure. OBJECTIVE: The study aimed to develop a
consensus statement on the application of laparoscopic surgery for GBC based on
expert opinions. METHODS: A consensus meeting among experts was held on September
10, 2016, in Seoul, Korea. RESULTS: Early concerns regarding port site/peritoneal
metastasis after laparoscopic surgery have been abated by improved preoperative
recognition of GBC and careful manipulation to avoid bile spillage. There is no
evidence that laparoscopic surgery is associated with decreased survival compared
with open surgery in patients with early-stage GBC if definitive resection
during/after laparoscopic cholecystectomy is performed. Although experience with
laparoscopic extended cholecystectomy for GBC has been limited to a few experts,
the postoperative and survival outcomes were similar between laparoscopic and
open surgeries. Laparoscopic reoperation for postoperatively diagnosed GBC is
technically challenging, but its feasibility has been demonstrated by a few
experts. CONCLUSIONS: Laparoscopic surgery for GBC is still in the early phase of
the adoption curve, and more evidence is required to assess this procedure.
PMID- 29339661
TI - A Novel FOXL2 Mutation Implying Blepharophimosis-Ptosis-Epicanthus Inversus
Syndrome Type I.
AB - BACKGROUND/AIMS: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a
rare autosomal dominant disease caused by FOXL2 gene mutations, and it is
clinically characterized by an eyelid malformation associated (type I) or not
(type II) with premature ovarian failure (POF). Functional study of novel
mutations is especially critical for female patients, as it may allow the
prediction of infertility and early planning of an appropriate therapy. METHODS:
A clinical and molecular genetic investigation was performed in all members of a
Chinese family with BPES. Genomic DNA was extracted, and the FOXL2 coding region
was sequenced. Subcellular localization was performed by confocal microscopy.
Transactivation studies were performed by real-time PCR, dual luciferase reporter
assays and electrophoretic mobility shift assays. RESULTS: A novel deletion
mutation (C.634_641 del, CCCATGC) between the forkhead domain and the polyalanine
domain was found, resulting in a frameshift mutation and a truncated protein.
Functional studies showed a strong cytoplasmic mislocalization and abnormal
transactivation activity, implying a type I kind mutation with a large chance of
infertility. CONCLUSION: This study identifies that this mutation indicates the
probability of developing into POF and shows the importance and necessity of
early recognition of BPES type through mutation testing for female patients.
Prompt personalized therapy and follow-up is of great clinical significance for
female patients carrying this kind of mutation.
PMID- 29339662
TI - Cytogenetic Characterization of Eight Odonata Species Originating from the
Curonian Spit (the Baltic Sea, Russia) Using C-Banding and FISH with 18S rDNA and
Telomeric (TTAGG)n Probes.
AB - We studied the karyotypes of 8 dragonfly species originating from the Curonian
Spit (the Baltic Sea, Russia) using C-banding and FISH with 18S rDNA and "insect"
telomeric (TTAGG)n probes. Our results show that Leucorrhinia rubicunda,
Libellula depressa, L. quadrimaculata, Orthetrum cancellatum, Sympetrum danae,
and S. vulgatum from the family Libellulidae, as well as Cordulia aenea and
Epitheca bimaculata from the family Corduliidae share 2n = 25 (24 + X) in males,
with a minute pair of m-chromosomes being present in every karyotype except for
that of C. aenea. Major rDNA clusters are located on one of the large pairs of
autosomes in all the species. No hybridization signals were obtained by FISH with
the (TTAGG)n probe in the examined species with the only exception of S.
vulgatum. In this species, clear signals were detected at the ends of almost all
chromosomes. This finding raises the possibility that in Odonata the canonical
"insect" (TTAGG)n telomeric repeat is in fact present but in very low copy number
and is consequently difficult to detect by in situ hybridization. We conclude
that more work needs to be done to answer questions about the organization of
telomeres in this very ancient and thus phylogenetically important insect order.
PMID- 29339663
TI - Evaluation of Magnetic Resonance Imaging/Ultrasound-Fusion Biopsy in Patients
with Low-Risk Prostate Cancer Under Active Surveillance Undergoing Surveillance
Biopsy.
AB - INTRODUCTION: Targeted biopsy of tumour-suspicious lesions detected in
multiparametric magnetic resonance imaging (mpMRI) plays an increasing role in
the active surveillance (AS) of patients with low-risk prostate cancer (PCa). The
aim of this study was to compare MRI/ultrasound-fusion biopsy (fusPbx) with
systematic biopsy (sysPbx) in patients undergoing biopsy for AS. METHODS:
Patients undergoing mpMRI and transperineal fusPbx combined with transrectal
sysPbx (comPbx) as surveillance biopsy were investigated. The detection of
Gleason score upgrading and reclassification according to Prostate Cancer
Research International Active Surveillance criteria were evaluated. RESULTS:
Eighty-three patients were enrolled. PCa upgrading was detected in 39% by fusPbx
and in 37% by sysPbx (p = 1.0). The percentage of patients who were reclassified
in fusPbx and sysPbx (p = 0.45) were 64 and 59% respectively. ComPbx detected
more frequently tumour upgrading than fusPbx (71 vs. 64%, p = 0.016) and sysPbx
(71 vs. 59%, p < 0.001) and more patients had to be reclassified after comPbx
than after fusPbx or sysPbx alone. CONCLUSIONS: The combination of fusPbx and
sysPbx outperforms both modalities alone with regard to the detection of
upgrading and reclassification in patients under AS. Because a high missing rate
of significant PCa still exists in both biopsy modalities, a combination of
fusPbx and sysPbx should be recommended in these patients.
PMID- 29339664
TI - Cenesthopathy and Subjective Cognitive Complaints: An Exploratory Study in
Schizophrenia.
AB - BACKGROUND/AIMS: Cenesthopathy is mainly associated with schizophrenia; however,
its neurobiological basis is nowadays unclear. The general objective was to
explore clinical correlates of cenesthopathy and subjective cognitive complaints
in schizophrenia. METHODS: Participants (n = 30) meeting DSM-IV criteria for
psychotic disorder were recruited from a psychiatry unit and assessed with:
Association for Methodology and Documentation in Psychiatry (AMDP) system,
Positive and Negative Syndrome Scale, Frankfurt Complaint Questionnaire (FCQ),
and the Bonn Scale for the Assessment of Basic Symptoms (BSABS). For quantitative
variables, means and Spearman correlation coefficients were calculated. Linear
regression following backward method and principal component analysis with
varimax rotation were used. RESULTS: 83.3% of subjects (73.3% male, mean age,
31.5 years) presented any type of cenesthopathy; all types of cenesthetic basic
symptoms were found. Cenesthetic basic symptoms significantly correlated with the
AMDP category "fear and anancasm," FCQ total score, and BSABS cognitive thought
disturbances. In the regression analysis only 1 predictor, cognitive thought
disturbances, entered the model. In the principal component analysis, a main
component which accounted for 22.69% of the variance was found. CONCLUSIONS:
Cenesthopathy, as assessed with the Bonn Scale (BSABS), is mainly associated with
cog-nitive abnormalities including disturbances of thought initiative and mental
intentionality, of receptive speech, and subjective retardation or pressure of
thoughts.
PMID- 29339665
TI - Novel Translational Research Methodology and the Prospect to a Better
Understanding of Neurodegenerative Disease.
PMID- 29339666
TI - Preventive Cold Acclimation Augments the Reparative Function of Endothelial
Progenitor Cells in Mice.
AB - BACKGROUND/AIMS: Chronic cold exposure may increase energy expenditure and
contribute to counteracting obesity, an important risk factor for
cerebrocardiovascular diseases. This study sought to evaluate whether preventive
cold acclimation before ischemia onset might be a promising option for preventing
cerebral ischemic injury. METHODS: After a 14-day cold acclimation period, young
and aged mice were subjected to permanent cerebral ischemia, and histological
analyses and behavioral tests were performed. Mouse endothelial progenitor cells
(EPCs) were isolated, their function and number were determined, and the effects
of EPC transplantation on cerebral ischemic injury were investigated. RESULTS:
Preventive cold acclimation before ischemia onset increased EPC function,
promoted ischemic brain angiogenesis, protected against cerebral ischemic injury,
and improved long-term stroke outcomes in young mice. In addition, transplanted
EPCs from cold-exposed mice had a greater ability to reduce cerebral ischemic
injury and promote local angiogenesis compared to those from control mice, and
EPCs from donor animals could integrate into the recipient ischemic murine brain.
Furthermore, transplanted EPCs might exert paracrine effects on cerebral ischemic
injury, which could be improved by preventive cold acclimation. Moreover,
preventive cold acclimation could also enhance EPC function, promote local
angiogenesis, and protect against cerebral ischemic injury in aged mice.
CONCLUSIONS: Preventive cold acclimation before ischemia onset improved long-term
stroke outcomes in mice at least in part via promoting the reparative function of
EPC. Our findings imply that a variable indoor environment with frequent cold
exposure might benefit individuals at high risk for stroke.
PMID- 29339667
TI - Improving Laboratory Assessment in Disorders of Sex Development through a
Multidisciplinary Network.
AB - The aim of the European Reference Network for Rare Endocrine Disorders (Endo-ERN)
is to ensure equal access to high-quality care for all those affected by a rare
endocrine condition across Europe, such as a disorder/difference of sex
development (DSD), both for children and adults. Although differences in
resources, health care systems, and health insurances between the European
countries are challenging and require political action, a European laboratory
network within Endo-ERN could improve the diagnostic process in individuals with
DSD, building on the work done by previous European collaborations such as the
COST action DSDnet. In close collaboration, clinicians and laboratory specialists
must make every effort to standardize diagnostic protocols, achieve necessary
harmonization of various laboratory tests, e.g., the hCG stimulation test, and
implement an external quality control system. This should ideally result in
comparable quality across the network centers allowing the sharing of reference
values. This would not only improve patient care but also greatly facilitate
research.
PMID- 29339668
TI - Proinflammatory Cytokines and Oxidative Stress Decrease the Transport of Dopamine
Precursor Tyrosine in Human Fibroblasts.
AB - BACKGROUND: Proinflammatory cytokines and oxidative stress responses have been
extensively implicated in the pathophysiology of neuropsychiatric disorders over
the past 2 decades. Moreover, disturbed transport of the dopamine precursor
(i.e., the amino acid tyrosine) has been demonstrated, in different studies,
across fibroblast cell membranes obtained from neuropsychiatric patients.
However, the role and influences of proinflammatory cytokines and oxidative
stress, and the reasons for disturbed tyrosine transport in neuropsychiatric
disorders, are still not evaluated. AIMS: The present study aimed to assess the
role of proinflammatory cytokines and oxidative stress, indicated in many
neuropsychiatric disorders, in tyrosine transportation, by using human skin
derived fibroblasts. METHODS: Fibroblasts obtained from a healthy control were
used in this study. Fibroblasts were treated with proinflammatory cytokines (IL
1beta, IFN-gamma, IL-6, TNF-alpha), their combinations, and oxidative stress,
optimized for concentrations and incubation time, to analyze the uptake of 14C
tyrosine compared to untreated controls. RESULTS AND CONCLUSION: This study
demonstrates that proinflammatory cytokines and oxidative stress decrease the
transport of tyrosine (47% and 33%, respectively), which can alter dopamine
synthesis. The functionality of the tyrosine transporter could be a new potential
biomarker to target for discovering new drugs to counteract the effects of
proinflammatory cytokines and oxidative stress in the pathophysiology of
neuropsychiatric disorders.
PMID- 29339669
TI - Signalling molecules in jaw bones and gingival tissues of patients with Class II
and Class III dentofacial deformities.
AB - OBJECTIVES: To detect signalling molecule specificities in jaw bone growth zones
in skeletal class II and class III patients and compare them to those of a
control group. MATERIAL AND METHODS: Twenty skeletal Class II and 20 skeletal
Class III patients who underwent orthognathic surgery treatment were in the study
group and five skeletal Class I patients who had impacted third molars extracted
were in the control group. During the orthognathic surgery, tissue samples were
taken from the tuber maxillae, ramus mandibulae anterior and posterior part
together with mucosa from the gingival transitory fold in the second molar region
of the lower jaw. The samples were stained to detect TGF-beta, BMP2/4, FGFR1,
VEGF, OC, OP and MMP2 expression. The distributions of these factors were
assessed semiquantitatively. RESULTS: We observed significant expression of TGF
beta, BMP2/4, OC and OP in the bone tissue of the study group. FGFR1 expression
was more pronounced only in mucosa. VEGF and MMP2 were found only in some tissue
samples. More apoptotic cells were observed in the bone tissue and soft tissue of
the control patients than in those of the skeletal Class II and Class III
patients, in which apoptotic cell frequencies were relatively equal. CONCLUSION:
From bone tissue in tuber maxillae region the greater TGF-beta and BMP2/4
expression is seen in Class III and control groups, comparing to Class II. In
ramus mandibulae anterior part the expression of significant factors in bone
tissue growth (TGF-beta un BMP2/4) is higher in the control group and Class II
patients, while in ramus mandibulae posterior part higher expression of TGF-beta
and BMP2/4 is in Class III patients, comparing to Class II, which indicates to a
preserved growth potential in these jaw bone regions. More active bone
extracellular matrix protein (osteocalcin and osteopontin) expression in tuber
maxillae region both in class II and class III patient groups and different
expression in ramus mandibulae anterior part, prove to the bone mineralization
and metabolism activity changes, which, perhaps, characterize just these
dentofacial deformations.
PMID- 29339670
TI - Family history and risk factors for cleft lip and palate patients and their
associated anomalies.
AB - BACKGROUND AND AIMS: Several environmental and genetic issues have been suspected
as risk factors for oral clefts; and many studies have been conducted in this
regard; however, large socioeconomic impacts of cleft lip and or palate (CL/P)
justifies the need for further multifactorial researches. Current study aimed to
assess parental risk factors for CL/P and its associated malformations. MATERIAL
AND METHODS: Hospital records of 187 consecutive syndromic and non-syndromic
children with cleft lip and or palate (103 boys and 84 girls) with a mean age of
1.7 (SD 2.2) years and 190 consecutive non-cleft children (103 boys and 87 girls)
with a mean age of 2.8 (SD 2.2) years formed this study. Parental risk factors
and abnormalities and physical problems and anomalies were evaluated in all
subjects. RESULTS: Family history of clefts (OR 7.4; 95% CI), folic acid
consumption (OR 7.3; 95% CI) and consanguineous marriage (OR 3.2; 95% CI) were
quite strongly associated with increased risk of CL/P. In addition, all
congenital abnormalities and physical problems had significantly higher incidence
in CL/P patients. CONCLUSIONS: The findings of this study suggest that expecting
mothers of consanguineous marriage and families with a history of CL/P should be
extra cautious about the occurrence of CL/P.
PMID- 29339671
TI - Psychosocial factors correlated with children's dental anxiety.
AB - Authors developed an idea of seven blocks with different psychosocial factors
that could correlate with children's dental anxiety and explain its variance. Aim
of the study was to evaluate correlation between psychosocial factors and
children's dental anxiety. Totally, 240 randomly selected children (mean age
M=7.96, SD=2.61, range 4 to 12) and their parents took part in the study. Parents
evaluated their own (MDAS) and their children's anxiety (CFSS-DS). Psychosocial
factors were evaluated by a large questionnaire, developed for this study. Dental
status was fixed and child's behavior in dental setting was evaluated with
Frankl's scale. Pearson's correlation of CDA with all variables and stepwise
linear regression with the correlating variables within the seven psychosocial
factor blocks was performed. Dental experience and attitude factors (crying at
dentist and dental treatment with difficulties) as well as Children's personality
and behavior factors (general anxiety and children's behavior at dentist) gave
the most effect on CDA, totally explaining 56% and 54% of variance, respectively.
Children's medical experience and attitude factors (anxiety and caution towards
doctors) as well as Parental/information factors (parental dental anxiety,
promising prizes before treatment) explained 34% and 31% of CDA variance,
respectively. Socio-economic factors (number of children and mother's age)
explained 15%, but oral care habits and attitude (brushing as obligation) - 14%
of CDA variance. Family distress factors had no correlation with CDA and were
excluded of further analysis. Children's dental anxiety variance is at best
explained by Child's dental experience and attitude factors and Child's
personality and behavior factors.
PMID- 29339672
TI - Serum and salivary lactate dehydrogenase levels as biomarkers of tissue damage
among cigarette smokers. A biochemical study.
AB - OBJECTIVE: To estimate the serum and salivary lactate dehydrogenase levels in
cigarette smokers and non-smokers. MATERIALS AND METHODS: In this study lactate
dehydrogenase levels were estimated in 30 healthy individuals with no tobacco
related habits and in 30 patients with history of smoking cigarettes for a
minimum of 2 years using Spectrophotometry. RESULTS: The mean values for serum
and salivary lactate dehydrogenase levels were higher in cigarette smokers when
compared to non-smokers. Serum lactate dehydrogenase levels on comparison between
the groups was statistically significant (p=0.04). The values of salivary lactate
dehydrogenase levels between the groups was highly significant (p<0.001).
CONCLUSION: Cigarette smoking leads to an increase in serum as well as salivary
Lactate dehydrogenase levels as indicator of tissue damage in the oral cavity.
The present study indicates saliva as a better test medium than serum in
determination of lactate dehydrogenase levels.
PMID- 29339673
TI - Histopathological and microradiological features of peri-implantitis. A case
report.
AB - AIM: The aim of this study was to describe the histological characteristics of a
peri-implantitis case in the anterior maxilla. CASE REPORT: A dental implant
inserted in the missing upper right lateral incisor region has been removed with
its adjacent tissues. The samples were placed in 4% formalin for 10 days and,
were embedded in methacrylate prior to sawing and grinding. The samples were
processed with Donath's sawing and grinding technique, stained with toluidine
blue and mounted on high-sensitivity plates for histology and microradiography.
The structure of the connective tissue revealed that there was a lack of collagen
fibers running parallel to the implant surface. The connective tissue showed a
loose granulation tissue with medium-density lymphocyte infiltration and
neutrophilic leukocytes. In addition to the collagen loss in the infiltrated
tissue, an excessive bone resorption was present. Peripherally, the light
microscopy showed the osteoclasts and their adhesive apparatus which promote bone
resorption. CONCLUSION: With the increasing number of implants being placed, peri
implantitis has become much more prevalent. Every additional study focusing on
the characteristics of peri-implantitis would be beneficial to gain an
understanding of bone and soft tissue behavior around the implant and could help
to develop appropriate therapeutic approaches for peri-implant disease.
PMID- 29339674
TI - Relation between high serum hepcidin-25 level and subclinical atherosclerosis and
cardiovascular mortality in hemodialysis patients.
AB - OBJECTIVE: In hemodialysis (HD) patients, cardiovascular disease (CVD) is the
major cause of mortality and morbidity. In atherosclerotic diseases, iron gets
accumulated in the arterial wall. Hepcidin is an important hormone in iron
metabolism. Furthermore, hepcidin is associated with atherosclerotic disease.
Therefore, this study aims to investigate the relation of serum hepcidin-25 (SH
25) and sub-clinic atherosclerosis measured by carotid intima-media thickness
(CIMT) and mortality in HD patients. METHODS: We enrolled 82 HD patients in a
cross-control study. We measured SH-25 using ELISA kit and CIMT using high
resolution real-time ultrasonography. After 4 years of first assessment, we
investigated the relation between all-cause and cardiovascular mortality and SH
25 and CIMT. RESULTS: Two patients were excluded because of renal
transplantation. The survivors were younger (53.7+/-15.1 vs. 65.2+/-15.5; p<0.05)
and CIMT was lower (0.83+/-0.2 vs. 0.95+/-0.2; p<0.05); however, there was no
significant difference in SH-25 levels between the groups (29.1+/-13 vs. 32.4+/
22.4; p=0.767). The patients who died of CVD were significantly older (63.7+/
16.1 vs. 53.7+/-15.1; p<0.05) and had significantly higher CIMT (0.94+/-0.2 vs.
83+/-0.2; p<0.05). The SH-25 levels were statistically significantly higher in
patients who died of CVD (40.3+/-25 vs. 29.1+/-13; p<0.05). Linear regression
analysis showed a positive correlation between CIMT and SH-25 in the study
population and in those who died from CVD (r=0.41; p<0.05 and r=0.606; p<0.05,
respectively). CONCLUSION: This study suggests that hepcidin is effective in
cardiovascular mortality and pathophysiology of subclinical atherosclerosis in HD
patients.
PMID- 29339675
TI - Association of serum prolidase activity in patients with isolated coronary artery
ectasia.
AB - OBJECTIVE: Coronary artery ectasia (CAE) is defined as an angiographic
enlargement of a portion of the coronary artery between 1.5 and 2 times the
diameter of the adjacent normal coronary artery. It has been demonstrated that
increased serum prolidase activity (SPA) is associated with increased collagen
turnover. We aimed to analyze the relationship between CAE and serum SPA levels.
METHODS: This study used a prospective case protocol design. A total of 40
consecutive patients with isolated right CAE and normal coronary arteries (23
men, 17 women; mean age, 62.4+/-10.8 years) were evaluated. The control group
included the same number of consecutive patients with angiographically normal
coronary arteries (20 men, 20 women; mean age, 63.8+/-11.1 years). Clinical
characteristics, laboratory results, cardiovascular risk factors, and medication
use were recorded. SPA was measured using a spectrophotometer. Student's t-test,
Mann-Whitney U test, chi-square test, Pearson's and Spearman's correlations,
logistic regression analysis, and ROC curve analysis were used for statistical
analysis. RESULTS: SPA was significantly higher in the CAE group compared with
the control group (1635.2+/-492.0 U/L and 986.2+/-422.3 U/L, respectively;
p<0.001). The relationship of SPA with CAE proved to be significant (r=0.512;
p<0.001). SPA also served as an independent predictor of CAE (OR=1.003; 95% CI,
1.001-1.005; p=0.002). The SPA value of 1170 U/L was predictive of CAE, with a
sensitivity of 85% and specificity of 60% (AUC=0.854; 95% CI, 0.763-0.944;
p<0.001). CONCLUSION: The activity of this enzyme was significantly correlated
with CAE.
PMID- 29339676
TI - Electrical and histological remodeling of the pulmonary vein in 2K1C hypertensive
rats: Indication of initiation and maintenance of atrial fibrillation.
AB - OBJECTIVE: Hypertension is a significant risk factor for atrial fibrillation
(AF). The role of pulmonary vein (PV) remodeling in the mechanistic association
between hypertension and AF is not definitive. In this study, we aimed to
identify changes in the electrophysiology and histology in PVs in two-kidney, one
clip (2K1C) hypertensive rats. METHODS: Fifty male Sprague-Dawley rats were
classified into the 2K1C and sham-operated groups. The systolic blood pressure
was measured every 2 weeks. The left atrial diameter was measured by
transthoracic echocardiography. Left superior PV (LSPV) and left atrial (LA)
fibrosis was evaluated by Masson's trichrome staining. The expression of fibrosis
markers [angiotensin II (Ang II), transforming growth factor-beta1 (TGF-beta1),
matrix metalloproteinase-2 (MMP-2), and collagen I (Col I)] and ion channels
[Kir2.1, Kir2.3, Cav1.2, and Nav1.5] in LSVP was quantified by western blot.
Conventional microelectrodes were used to record the action potential duration at
90% repolarization (APD90) and effective refractory period (ERP) in isolated LA.
RESULTS: At 4 months, the 2K1C hypertensive rats developed LA dilation. Col
deposition in LSPV and left atrium and expression of TGF-beta1, MMP-2, and Col I
in LSPV were significantly increased in 2K1C hypertensive rats. In addition,
hypertension reduced the expression of Nav1.5 and Kir2.1, although there were no
significant differences in APD90; ERP; and expression of Ang II, Kir2.3, and
Cav1.2 between the two groups. CONCLUSION: Hypertension may lead to changes in
the electrophysiology and histology of rats PVs, which is characterized by
significant reduction in the expression of Nav1.5 and Kir2.1 and increase in
interstitial fibrosis. These observations may clarify the role of PVs in the
mechanistic association between hypertension and AF.
PMID- 29339677
TI - Acute myocardial infarction shortly after valve-in-valve transcatheter aortic
valve implantation successfully managedwith challenging percutaneous coronary
intervention.
AB - In recent years, transcatheter aortic valve implantation (TAVI) has been
considered a novel option for the management of surgically high-risk patients
requiring aortic valve replacement. Presently described is a case of acute
coronary syndrome (ACS) managed with a challenging primary percutaneous coronary
intervention (PCI) shortly after a valve-in-valve TAVI intervention. This case
highlights 2 important issues: PCI may be an option for the management of
coronary heart disease in patients after TAVI even in the setting of demanding
features associated with coronary osteal engagement, and secondly, TAVI may serve
as a potential risk factor for future coronary ischemic syndromes, largely due to
its potential adverse effects on coronary flow dynamics, etc. However, the latter
notion is quite speculative, and should be tested in further studies.
PMID- 29339678
TI - Endarteritis of coarctation of the aorta diagnosed with PET-CT.
AB - Infective endocarditis (IE) is an infectious disease that affects the endothelium
of the large intrathoracic vessels, heart valves, and intra-cardiac foreign body
material. A 20-year-old woman was admitted to the cardiology department with
complaints of fever and palpitations. Transthoracic echocardiography revealed a
bicuspid aortic valve, aortic root enlargement, and aortic coarctation.
Transesophageal echocardiography revealed a bicuspid aortic valve, but there was
no vegetation. Methicillin-sensitive Staphylococcus aureus was identified on a
blood culture. 18F-fluorodeoxyglucose positron emission tomography-computed
tomography (18F-FDG PET-CT) revealed increased intensive glucose uptake on the
dilated aortic segment adjacent to the distal coarctation zone. Several reports
have shown promising results for radio-labelled white blood cell single-photon
emission computed tomography and 18F-FDG PET-CT imaging in IE. To our knowledge,
this is the first described case in which PET-CT revealed endarteritis of the
descending aorta in a patient without prosthetic material.
PMID- 29339679
TI - A rare complication in a patient taking rivaroxaban: Alveolar hemorrhage.
AB - Alveolar hemorrhage (AH) is a heterogeneous clinical syndrome with a high
mortality rate that is characterized by extensive bleeding into the alveolar
spaces. AH usually develops secondary to immunological disease and, less
frequently, to drug use. Presently described is the case of an 86-year-old woman
with AH who had been using rivaroxaban for 6 months.
PMID- 29339680
TI - Case Image: Percutaneous approach to giant coronary artery aneurysm: successful
implantation of covered stent graft.
PMID- 29339681
TI - Case Image: Superdominant right coronary artery and left anterior descending
artery arising from the right coronary sinus: a rare coronary artery anomaly.
PMID- 29339682
TI - Case Image: A rare angiographic image of Vieussens' arterial ring associated with
coronary to pulmonary artery fistula.
PMID- 29339683
TI - Case Image: Double aortic arch presenting with respiratory disorders.
PMID- 29339684
TI - [2017 ESC focused update on dual antiplatelet therapy in coronary artery disease
developed in collaboration with EACTS: What is new?]
PMID- 29339685
TI - Intra-aortic balloon pump use in acute coronary syndrome: One size does not fit
all!
PMID- 29339686
TI - Clinical characteristics and outcomes of acute coronary syndrome patients with
intra-aortic balloon pump inserted in intensive cardiac care unit of a tertiary
clinic.
AB - OBJECTIVE: An intra-aortic balloon pump (IABP) is a mechanical support device
that is used in addition to pharmacological treatment of the failing heart in
intensive cardiac care unit (ICCU) patients. In the literature, there are limited
data regarding the clinical characteristics and in-hospital outcomes of acute
coronary syndrome patients in Turkey who had an IABP inserted during their ICCU
stay. This study is an analysis of the clinical characteristics and outcomes of
these acute coronary syndrome patients. METHODS: The data of patients who were
admitted to the ICCU between September 2014 and March 2017 were analyzed
retrospectively. The data were retrieved from the ICCU electronic database of the
clinic. A total of 142 patients treated with IABP were evaluated in the study.
All of the patients were in cardiogenic shock following percutaneous coronary
intervention, at the time of IABP insertion. RESULTS: The mean age of the
patients was 63.0+/-9.7 years and 66.2% were male. In-hospital mortality rate of
the study population was 54.9%. The patients were divided into 2 groups,
consisting of survivors and non-survivors of their hospitalization period.
Multivariate analysis after adjustment for the parameters in univariate analysis
revealed that ejection fraction, Thrombolysis in Myocardial Infarction flow score
of <=2 after the intervention, chronic renal failure, and serum lactate and
glucose levels were independent predictors of in-hospital mortality. CONCLUSION:
The mortality rate remains high despite IABP support in patients with acute
coronary syndrome. Patients who are identified as having a greater risk of
mortality according to admission parameters should be further treated with other
mechanical circulatory support devices.
PMID- 29339687
TI - Subclinical left ventricular systolic dysfunction in patients with severe aortic
stenosis: A speckle-tracking echocardiography study.
AB - OBJECTIVE: In patients with aortic stenosis (AS), the left ventricular (LV)
geometry changes due to the increased LV afterload. However, subclinical
myocardial dysfunction can develop despite a normal LV ejection fraction (EF).
This study was an investigation of subclinical LV systolic dysfunction in
patients with severe AS with a normal LV EF using a strain imaging method,
speckle-tracking echocardiography (STE), and an evaluation of its correlation
with novel indices to assess the severity of AS. METHODS: A total of 45
asymptomatic patients with severe AS and 25 age- and sex-matched controls without
any cardiac disease and with preserved LV EF (EF >=60%) were studied. In addition
to performing conventional echocardiography and STE-based strain imaging, novel
indices (energy loss index [ELI], valvulo-arterial impedance, systemic arterial
compliance) were also measured. RESULTS: The LV EF, and the LV end-diastolic and
end-systolic diameters were similar in the 2 groups. The LV longitudinal peak
systolic strain (10.66+/-1.15% to 19.66+/-2.62%; p=0.0001) and strain rate
(0.32+/-0.07 s-1 to 1.85+/-0.32 s-1; p=0.0001) were significantly impaired in the
study patients compared to the controls, demonstrating subclinical ventricular
systolic dysfunction. A significant positive correlation was observed between the
ELI and the LV strain/strain rate (r=0.45, p=0.002; r=0.55, p=0.0001,
respectively). CONCLUSION: Patients with severe AS develop subclinical LV
systolic dysfunction, despite a preserved EF. Novel strain imaging-based
echocardiographic techniques may provide additional data that can detect early
myocardial systolic deterioration in these patients.
PMID- 29339688
TI - Choice of treatment based on Turkish hypertension consensus report: Do we follow
the recommendations?
AB - OBJECTIVE: The aim of this study was to determine how often the recommendations
of the Turkish Hypertension Consensus Report are followed, and to draw attention
to the report. METHODS: The demographic information of 1000 patients diagnosed
with hypertension and the details of the antihypertensive medications prescribed
at the outpatient service of a tertiary care hospital were recorded, and the data
were compared with the recommendations of the report. RESULTS: The mean age of
the patients was 62+/-11 years. In all, 623 (62.3%) of the 1000 patients were
women, and 377 (37.7%) were men. A combination of an angiotensin II receptor
blocker (ARB) and a diuretic was the most frequently observed prescription. A
diuretic was the most used antihypertensive drug (58.7%), followed by an ARB
(48.8%). However, as a monotherapy, a calcium channel blocker (CCB) was the most
commonly used antihypertensive drug (19.2%). The most frequently used
antihypertensive drug group in older patients was diuretics (63.6%), as proposed
in the report. Beta blockers (49.1%) were used more often than expected. For the
diabetic group also, a diuretic (60.7%) was the most frequently used
antihypertensive drug, followed by an ARB (51.1%) and a CCB (45.2%). Angiotensin
converting enzyme (ACE) inhibitors (34.6%) were the fifth most preferred
antihypertensive drug class. However, when ACE inhibitors and ARBs were
considered as a single group, known as renin-angiotensin system (RAS) blockers,
these RAS blockers were the most prescribed antihypertensive drug class, followed
by diuretics. In the group of patients with coronary artery disease, treatment
was found to be generally consistent with the report, but the use of diuretics
was greater than expected. Lastly, 124 of 160 patients who had chronic kidney
disease were given RAS blocker therapy, which was in line with the consensus
report recommendations. CONCLUSION: Antihypertensive therapies were
individualized, as suggested by the consensus report. However, there are
proposals still to be considered in special patient groups.
PMID- 29339689
TI - Atherogenic index of plasma as a cardiovascular risk marker in manic, depressive,
and euthymic stages of bipolar disorder.
AB - OBJECTIVE: Individuals with bipolar disorder (BD) frequently suffer from
cardiovascular disease (CVD), and it is a leading cause of mortality. Clinicians
use routine laboratory tests, including a lipid profile, to predict
cardiovascular risk. In addition, a particular lipid ratio, the atherogenic index
of plasma (AIP), is a sensitive, new parameter that can be used to assess
highrisk groups. To our knowledge, this is the first study evaluating
cardiovascular risk via AIP in different stages of BD. METHODS: The study group
consisted of male patients with BD who were in a manic, depressive, or euthymic
state, and age- and gender-matched healthy controls. Lipid profiles were analyzed
and the AIP parameter of logarithm of triglyceride (TG) / high-density
lipoprotein cholesterol (HDLc) was calculated for all of the participants. The
significance level was set at p<0.05. RESULTS: A total of 44 BD patients
experiencing a manic episode, 35 depressive BD patients, 42 euthymic patients,
and 41 healthy controls matched for age, gender, and smoking status were enrolled
in the study. The AIP level was significantly different between groups (p=0.009).
Pairwise comparisons of the groups revealed that the AIP level of depressive
patients was significantly higher than that of the manic, euthymic, and control
groups (p=0.013, p=0.048, and p=0.021, respectively). The AIP level was
positively correlated with body mass index, waist circumference, metabolic
syndrome, total cholesterol, low-density lipoprotein, and triglyceride level, and
was negatively correlated with the HDLc level. CONCLUSION: In this study, male BD
patients in a depressive episode demonstrated an increase in cardiovascular risk.
The significant correlations between AIP and other conventional cardiovascular
risk factors indicate that AIP may be more useful to identify individuals with BD
at high risk for CVD than absolute lipid parameters.
PMID- 29339690
TI - The rationale and design of the national peripartum cardiomyopathy registries in
Turkey: The ARTEMIS-I and ARTEMIS-II studies.
AB - OBJECTIVE: Peripartum cardiomyopathy (PPCM) is left ventricular (LV) systolic
dysfunction with an ejection fraction of <=45% occurring in the later stages of
pregnancy or soon after delivery. Although various risk factors have been
identified, the exact cause of the disease is unknown. Unlike most countries in
the European region, Turkey has yet to determine the current PPCM burden. A
registry for this purpose does not exist. To close this gap, the A RegisTry of
pEripartuM cardIomyopathy in Turkish patientS (ARTEMIS-I and ARTEMIS-II), was
planned and endorsed by the Turkish Society of Cardiology. The aim of this
manuscript is to describe the rationale and design of the ARTEMIS-I and ARTEMIS
II registries. METHODS: ARTEMIS was designed to be the nationwide PPCM registry
of Turkey, with the goal of identifying problems and opportunities while
improving quality and consistency in the medical care of PPCM patients. A second
goal is to determine the clinical characteristics pertinent to patients in this
region. The ARTEMIS registry will consist of 2 arms. All secondary and tertiary
cardiology centers have been electronically invited to participate in ARTEMIS-I,
which will be conducted to assess the current standard of care and outcome
measures. Centers will be asked to enroll PPCM patients admitted to their clinic
in last 5 years retrospectively. Eligibility criteria will consist of pregnant or
early postpartum woman without a previous history of heart failure (HF) or known
pathology associated with HF, LV ejection fraction <=45%, and exclusion of other
causes of LV systolic dysfunction. ARTEMIS-II will consist of the prospective
enrollment of patients. CONCLUSION: The nationwide PPCM registries, ARTEMIS-I and
ARTEMIS-II, are designed to determine the current status of medical care, provide
insights into nature of the disease, and suggest solutions on how to improve care
and outcomes in these patients.
PMID- 29339691
TI - Rationale, design, and methodology of the Evaluation of Perceptions, Knowledge,
and Compliance with the Guidelines in Real Life Practice: A Survey on the Under
treatment of Hypercholesterolemia.
AB - OBJECTIVE: A wide gap exists between dyslipidemia guidelines and their
implementation in the real world, which is primarily attributed to physician and
patient compliance. The aim of this study is to determine physician and patient
adherence to dyslipidemia guidelines and various influential factors. METHODS:
The Evaluation of Perceptions, Knowledge, and Compliance with the Guidelines in
Real Life Practice: A Survey on the Under-treatment of Hypercholesterolemia
(EPHESUS) trial (ClinicalTrials.gov number NCT02608645) will be an observational,
multicenter, non-interventional study. The study targets enrollment of 2000
patients from 50 locations across Turkey. All of the data will be collected in a
single visit and current clinical practice will be evaluated. A cross-sectional
survey of public perception and knowledge of cholesterol treatment among Turkish
adults will be performed. All consecutive patients admitted to cardiology clinics
who are in the secondary prevention group (coronary heart disease, peripheral
artery disease, atherosclerotic cerebrovascular disease) and who are in the high
risk primary prevention group (type 2 diabetes mellitus with no prior known
coronary heart disease; patients who had markedly elevated single risk factors,
in particular, cholesterol >8 mmol/L [>310 mg/dL], blood pressure >=180/110 mmHg,
a calculated Systematic Coronary Risk Evaluation [SCORE] >=5%, or <10% 10-year
risk of fatal cardiovascular disease) will be included. Demographic, lifestyle,
medical, and therapeutic data will be collected with a survey designed for the
study. CONCLUSION: The EPHESUS registry will be the largest study conducted in
Turkey evaluating the adherence to dyslipidemia guidelines both in secondary and
high-risk primary prevention patients.
PMID- 29339692
TI - Transvenous extraction of a 26-year-old Accufix atrial lead using TightRail
rotating dilator sheath.
AB - With the increasing number of implanted pacemakers and implantable cardioverter
defibrillators, removal is required more frequently. Presently described is the
transvenous extraction of a 26-year-old Accufix atrial lead using a mechanical
dilator sheath. A 50-year-old male patient was admitted to the clinic with a
pacemaker pocket infection. The atrial lead was an Accufix Bipolar J-Atrial
active fixation lead, a model that was recalled in 1994, after reports of 2
deaths and 2 nonfatal injuries related to protrusion of the J retention wire.
Both the atrial and ventricular leads were extracted using a mechanical dilator
sheath. The Pacemaker Lead Extraction with the Excimer Sheath (PLEXES) Trial
reported that of the 57 Accufix leads randomized to a non-laser approach, only
47% were removed successfully, compared with 96% of laser-randomized cases. Since
laser sheaths are not available in Turkey, use of a mechanical dilator sheath was
required. To our knowledge, this is the oldest Accufix lead extracted with a non
laser sheath. During the extraction of the ventricular lead, the tip of the lead
broke off inside the right ventricle and the residual part was left inside the
heart. During 3 months of follow-up, no signs of infection or any other
undesirable events were encountered.
PMID- 29339693
TI - Simultaneous total occlusion of two coronary arteries associated with use of
drospirenone-ethinyl estradiol (oral contraceptive).
AB - Although the use of oral contraceptives is associated with an increased risk of
venous thromboembolic disease, the risk of myocardial infarction (MI) is unclear.
A new, third-generation contraceptive agent, drospirenone-ethinyl estradiol,
which contains less estrogen and a new progestogen, drospirenone, in a different
combination, has been considered more reliable in terms of risk of MI. However,
there have been some cases of MI associated with the use of drospirenone-ethinyl
estradiol, despite the protective effects of this oral contraceptive. In this
report, a 33-year-old woman who had used drospirenone-ethinyl estradiol for 6
months was admitted with MI and symptoms of cardiogenic shock. Coronary
angiography revealed the total occlusion of 2 coronary arteries and so
percutaneous coronary intervention was performed. To the best of our knowledge,
this is the first case report of simultaneous total occlusion of 2 coronary
arteries associated with the use of drospirenone-ethinyl estradiol in the English
language medical literature.
PMID- 29339694
TI - Aortic alpha-smooth muscle actin expressions in aortic disorders and coronary
artery disease: An immunohistochemical study.
AB - OBJECTIVE: The is to report immunohistochemical observations of aortic alpha
smooth muscle actin (SMA) expressions in patients with aortic aneurysm, acute
aortic dissection, and coronary artery disease and to discuss phenotypic
switching of smooth muscle cells (SMCs) of these lesions. METHODS: Forty-nine
consecutive patients scheduled for surgical treatment for acute type A aortic
dissection (20 patients), aortic aneurysm (9 patients), and coronary artery
disease (20 patients) were included. Surgical specimens of the aorta were
obtained and prepared for hematoxylin and eosin and immunohistochemical
stainings. RESULTS: A comparison of aortic structural changes between the three
groups showed that patients with coronary artery disease had the least severe
aorta degeneration with the most intense alpha-SMA positivity. Aortic structural
impairment was the most severe in patients with aortic dissection, whereas alpha
SMA positivity was more intense in patients with aortic dissection than in those
with aortic aneurysm. CONCLUSION: Disparities in alpha-SMA expressions in the
aortic tissues of the three groups represent the extent of SMC degenerations or a
phenotypic switching between contractile and synthetic SMCs. The results imply
severe SMC degenerations in patients with aortic aneurysm, which may be
beneficial because of the production of extracellular matrix necessary for
healing of the vascular wall, but severe disruptions in elastic fibers in
patients with aortic dissection. Patients with coronary artery disease show
slight SMC degeneration and phenotypic switching among the three groups. The
possible apoptotic and genetic mechanisms of aortic structural impairments
warrant further elaborations.
PMID- 29339695
TI - Smooth muscle phenotype in aortic diseases: Are there other histopathological
markers besides contractile myofibrils?
PMID- 29339696
TI - Chronic ethanol increases calcium/calmodulin-dependent protein kinaseIIdelta gene
expression and decreases monoamine oxidase amount in rat heart muscles: Rescue
effect of Zingiber officinale (ginger) extract.
AB - OBJECTIVE: Association between chronic alcohol intake and cardiac abnormality is
well known; however, the precise underlying molecular mediators involved in
ethanol-induced heart abnormalities remain elusive. This study investigated the
effect of chronic ethanol exposure on calcium/calmodulin-dependent protein kinase
IIdelta (CaMKIIdelta) gene expression and monoamine oxidase (MAO) levels and
histological changes in rat heart. It was also planned to find out whether
Zingiber officinale (ginger) extract mitigated the abnormalities induced by
ethanol in rat heart. METHODS: Male wistar rats were divided into three groups of
eight animals each: control, ethanol, and ginger extract treated-ethanol (GETE)
groups. RESULTS: After 6 weeks of treatment, the results revealed a significant
increase in CaMKIIdeltatotal and isoforms delta2 and delta3 of CaMKIIdelta gene
expression as well as a significant decrease in the MAO levels in the ethanol
group compared to that in the control group. Moreover, compared to the control
group, the ethanol group showed histological changes, such as fibrosis, heart
muscle cells proliferation, myocyte hypertrophy, vacuolization, and focal
lymphocytic infiltration. Consumption of ginger extract along with ethanol
ameliorated CaMKIIdeltatotal. In addition, compared to the ethanol group,
isoforms gene expression changed and increased the reduced MAO levels and
mitigated heart structural changes. CONCLUSION: These findings indicate that
ethanol-induced heart abnormalities may, in part, be associated with Ca2+
homeostasis changes mediated by overexpression of CaMKIIdelta gene and the
decrease of MAO levels and that these effects can be alleviated by using ginger
extract as an antioxidant and anti-inflammatory agent.
PMID- 29339697
TI - The value of real-time myocardial contrast echocardiography for detecting
coronary microcirculation function in coronary artery disease patients.
AB - OBJECTIVE: The aim of this study was to evaluate the value of real-time
myocardial contrast echocardiography (RT-MCE) for detecting coronary
microcirculation (CM) function in coronary artery disease (CAD) patients.
METHODS: Sixty-five consecutive patients were divided into CAD (n=52) and no-CAD
(n=13) groups using coronary angiography (CAG). All patients underwent RT-MCE at
rest and CAG within 1 week after RT-MCE. The ventricular segments in CAD patients
were divided semi-quantitatively into ischemic and non-ischemic myocardial groups
based on RT-MCE images. Myocardial blood volume (A), myocardial blood flow
velocity (beta), and mean myocardial blood flow (Axbeta) were obtained. The
Gensini scores were calculated for CAD patients. The receiver operating
characteristic (ROC) curve areas of A, beta, and Axbeta were calculated to assess
CM function in CAD patients. RESULTS: A total of 798 and 204 segments were
investigated in the CAD and non-CAD groups, respectively. In CAD patients, 332
ischemic and 466 non-ischemic segments were identified. The values of A, beta,
and Axbeta were significantly different among non-CAD, CAD, ischemic, and
nonischemic groups. ROC curve areas of A, beta, and Axbeta were 0.85, 0.79, and
0.83, respectively, and significant differences were observed in these values
among three Gensini score groups of the CAD patients. CONCLUSION: Varying degrees
of CM function deterioration was observed in CAD patients both in ischemic and
non-ischemic areas, with the deterioration being more sever in the former.
PMID- 29339698
TI - Association of Interleukin-1 Gene cluster polymorphisms with coronary slow flow
phenomenon.
AB - OBJECTIVE: Coronary slow flow phenomenon (CSFP) is characterized by the decreased
rate of contrast progression in epicardial coronary arteries in the absence of
significant coronary stenosis. Mounting evidence has showed a significant
association between inflammation and CSFP severity. This study aimed to evaluate
possible associations between interleukin-1 receptor antagonist (IL-1ra) gene
variable number tandem repeat (VNTR), IL-1beta -511 single nucleotide (SNP), and
IL-1beta+3954 SNP mutations with CSFP. METHODS: Forty-eight patients with CSFP
and 62 controls with angiographically normal coronary arteries were prospectively
enrolled in the study. Genotypes were assessed using the polymerase chain
reaction (PCR)-based restriction fragment length polymorphism (PCR-RFLP)
technique. RESULTS: Homozygote genotype for allele 2 of+3954 C>T 2/2 genotype was
significantly more frequent in patients with CSFP than in the control group,
whereas 1/2 genotype was more frequent in the control group (35.4% versus 14.5%
for 2/2 genotype and 25% versus 35.5% for 1/2 genotype in CSFP and control
groups, respectively, X2=6.6; p=0.04). The allelic frequency of allele 2 of this
polymorphism was significantly higher in the CSFP group than in the control group
(47.9% versus 28.6% in the control group, X2=5.6; p=0.02). However, there was no
significant difference with regard to genotype or allelic frequencies of IL-1ra
VNTR or IL-1beta -511 SNP polymorphisms between patients with CSFP and controls.
CONCLUSION: IL-1beta+3954 SNP mutations are significantly more common in patients
with CSFP. It may suggest that the tendency for inflammation may contribute to
the presence of this phenomenon.
PMID- 29339699
TI - Impact of gender and age on the association of the BUD13-ZNF259 rs964184
polymorphism with coronary heart disease.
AB - OBJECTIVE: Coronary heart disease (CHD) is the most common cause of death
worldwide. This study aimed to validate the association of the rs964184
polymorphism with the CHD risk and included 874 CHD patients and 776 controls.
METHODS: rs964184 polymorphism genotyping was performed using Tm-shift polymerase
chain reaction. RESULTS: A strong association of the rs964184 polymorphism with
CHD was found (genotype: X2=14.365, p=0.001; allele: X2=14.191, p=1.67x10-4;
power=0.965). Gender analysis revealed a significant association only in males
(genotype: X2=12.387, p=0.002; allele: X2=12.404, p=4.32x10-4; OR=1.467, 95%
CI=1.185-1.817, power=0.945). Age and gender analyses revealed significant
associations of the rs964184 polymorphism with CHD in males between the ages of
55 and 65 years (genotype: X2=10.070, p=0.007; allele: X2=10.077, p=0.002;
OR=1.706, 95% CI=1.224-2.377, power=0.996) and in females older than 65 years
(genotype: X2=9.462, p=0.009; allele: X2=9.560, p=0.002; OR=2.112, 95% CI=1.308
3.412, power=0.994). Further subgroup analysis suggested that rs964184 genotypes
were significantly associated with TG levels in the patients (r=0.191, adjusted
p=1.05x10-5) and controls (r=0.101, adjusted p=0.026). CONCLUSION: Our results
indicate that both gender and age have great impacts on the association of the
rs964184 polymorphism with CHD among Chinese.
PMID- 29339700
TI - Assessment of the relationship between reperfusion success and T-peak to T-end
interval in patients with ST elevation myocardial infarction treated with
percutaneous coronary intervention.
AB - OBJECTIVE: T-peak-T-end (TPE) interval, which represents the dispersion of
repolarization, is defined as the interval between the peak and end of the T
wave, and is associated with increased malignant ventricular arrhythmia and
sudden cardiac death (SCD) in patients with ST elevation myocardial infarction
(STEMI). Although prolonged TPE interval is associated with poor short- and long
term outcomes, even in patients with STEMI treated with successful primary
percutaneous coronary intervention (pPCI), clinical, angiographic, and laboratory
parameters that affect TPE remain to be elucidated. The aim of our study was to
evaluate the potential relationship between prolonged TPE interval and
reperfusion success using ST segment resolution (STR) in patients with STEMI
undergoing pPCI. METHODS: In the current study, 218 consecutive patients with
STEMI who underwent pPCI were enrolled; after exclusion, 164 patients were
included in the study population. RESULTS: Patients were divided into two groups
according to the presence of complete (STR%>=70) or incomplete (STR%<70) STR.
Preprocedural corrected TPE (cTPEPRE;116+/-21 ms vs. 108+/-21 ms; p=0.027),
postprocedural TPE (TPEPOST; 107+/-16 ms vs. 92+/-21 ms; p<0.001), and
postprocedural cTPE (cTPEPOST; 119+/-19 ms vs. 102+/-17 ms; p<0.001) intervals
were significantly longer in patients with incomplete STR than in patients with
complete STR, whereas there was no statistically significant difference between
the two groups in terms of pre- and postprocedural and corrected QT intervals.
cTPEPRE and cTPEPOST were found to be independent predictors for incomplete STR.
CONCLUSION: To our knowledge, this is the first study that evaluated the
relationship between TPE interval and no-reflow defined by STR in patients with
STEMI who were treated with pPCI.
PMID- 29339701
TI - Subclinical reduction in left ventricular function using triplane and 2D speckle
tracking echocardiography after anthracycline exposure in children.
AB - OBJECTIVE: Speckle tracking echocardiography (STE) enables global and regional
evaluation of the left ventricle (LV); therefore, it is the most useful method
for detecting subclinical dysfunction in patients exposed to cardiotoxic agents.
A novel technique triplane (3P) echocardiography also allows single beat
assessment of LV global longitudinal strain values. We firstly aimed to
demonstrate both two-dimensional (2D)- and 3PSTE-derived LV global longitudinal
strain measurements in children after anthracycline exposure. METHODS: This study
included 23 cross-sectionally enrolled asymptomatic pediatric cancer patients who
received anthracycline chemotherapy and 17 healthy controls matched by age,
gender, and body surface area. All subjects underwent detailed 2D, Doppler, 2D
STE, and 3P-STE for assessment of LV function. The patients had received a median
cumulative dose of 150 mg/m2. RESULTS: 1. From "Pulsed" Doppler-based
measurements, only pulmonary vein flow ratio showed a significant difference
between the groups. 2. When measurements were taken from the interventricular
septum, the patients' ejection time values decreased significantly and their
myocardial performance index values increased significantly; when the
measurements were taken from the LV free wall, the peak systolic velocities
showed a statistically significant difference. 3. Both 2D- and 3P-STE-derived
longitudinal myocardial deformation values of LV were lower in the patient group.
4. 2D-STE-derived LV circumferential strain values were decreased in the patient
group, whereas radial strain values were not significantly different compared
with matched controls. CONCLUSION: Using Doppler and 2D- and 3P-STE methods, this
study confirmed the subclinical LV dysfunction in patients after anthracycline
exposure.
PMID- 29339702
TI - Efficacy and safety of oral anticoagulation in elderly patients with atrial
fibrillation.
AB - Elderly patients with atrial fibrillation are at a higher risk of both ischemic
and bleeding events compared with younger patients; therefore, balancing risks
and benefits of antithrombotic strategies in this population is crucial. Recent
studies have shown that because the risk of stroke increases with age more than
the risk of bleeding, the absolute benefit of oral anticoagulation is the highest
in elderly patients in whom it outweighs the risk of bleeding. Direct oral
anticoagulants (DOACs) have been developed as a treatment for the prevention of
cardioembolic stroke to overcome some limitations of warfarin, such as the need
for frequent monitoring, labile INR values requiring frequent dose adjustment,
dietary and drugs interactions, and increased risk of intracranial bleeding.
Despite the better safety profiles of DOACs compared with warfarin, elderly
patients often remain undertreated because of the fear of bleeding complications.
This review summarizes current evidence regarding the risks of thromboembolisms
and bleeding in different antithrombotic strategies in elderly patients (aged
>=75 years) with atrial fibrillation, including data from the warfarin-controlled
phase 3 DOACs trials.
PMID- 29339703
TI - A case of asymptomatic large aortopulmonary window in an adult: Role of cardiac
CT, CMRI, and 3D printing technology.
PMID- 29339704
TI - Valve-sparing aortic root replacement in Loeys-Dietz syndrome and a novel
mutation in TGFBR2.
PMID- 29339705
TI - A sad story of a man with two ventricles.
PMID- 29339706
TI - Tolvaptan should be used very carefully in very elderly patients.
PMID- 29339707
TI - Author's Reply.
PMID- 29339708
TI - Simultaneous subacute thrombosis in two new-generation drug-eluting stents in
different vessels.
PMID- 29339709
TI - Short-term evolution of cardiac structure and function in patients on maintenance
hemodialysis for end-stage renal disease: A quasi-experimental, non-randomized,
evaluation echocardiography study in Cameroon, sub-Saharan Africa.
PMID- 29339710
TI - A case of acute intrastent thrombosis accompanied by arterial thrombosis in the
lower extremities after percutaneous coronary intervention.
PMID- 29339711
TI - Unusual combination of mitral valve prolapse, bicuspid aortic valve, and
ventricular septal defect restricted by the tricuspid septal leaflet.
PMID- 29339712
TI - A New Year, A New Time.
PMID- 29339713
TI - Neuroprotective effect of selective antegrade cerebral perfusion during prolonged
deep hypothermic circulatory arrest: Cerebral metabolism evidence in a pig model.
AB - OBJECTIVE: The aim of this study was to elucidate the mechanism of cerebral
injury and to evaluate selective antegrade cerebral perfusion (SACP) as a
superior neuroprotective strategy for prolonged deep hypothermic circulatory
arrest (DHCA). METHODS: Twelve pigs (6-8-week old) were randomly assigned to DHCA
alone (n=6) and DHCA with SACP (n=6) at 18 degrees C for 80 min groups. Serum
S100 was determined using an immunoassay analyzer. The concentrations of cerebral
dialysate glucose, lactate, pyruvate, glycerol, and glutamate were measured using
a microdialysis analyzer. RESULTS: Compared with a peak at T4 (after 60 min of
rewarming) in the DHCA group, the serum S100 in the SACP group was significantly
lower throughout the study. The DHCA group was susceptible to significant
increases in the levels of lactate, glycerol, and glutamate and the ratio of
lactate/pyruvate as well as decreases in the level of glucose. These
microdialysis variables showed only minor changes in the SACP group. There was a
positive correlation between cerebral lactate and intracranial pressure during
reperfusion in the DHCA group. However, the apoptosis index and C-FOS protein
levels were lower in the SACP group. CONCLUSION: Metabolic dysfunction is
involved in the mechanism of cerebral injury. SACP is a superior neuroprotective
strategy for both mild and prolonged DHCA.
PMID- 29339714
TI - Stent thrombosis in patients with drug--eluting stents and bioresorbable vascular
scaffolds: the feared complication.
AB - The percutaneous coronary intervention (PCI) has undergone rapid evolution over
the last 40 years and has become one of the most widely performed medical
procedures. The introduction of intracoronary stents has improved the safety and
efficacy of PCI. However, with the advent of stenting, a new potentially fatal
enemy has emerged: stent thrombosis. Ever since, adjunct pharmacological therapy,
stent technique, and technology have been adjusted to reduce the risk of stent
thrombosis. The aim of the present article is to provide an overview of the past,
present, and future aspects of PCI in relation to stent thrombosis.
PMID- 29339715
TI - Caveolin-1 Inhibits Proliferation, Migration, and Invasion of Human Colorectal
Cancer Cells by Suppressing Phosphorylation of Epidermal Growth Factor Receptor.
AB - BACKGROUND Although downregulation of caveolin-1 (Cav-1), which is a key
constituent of membrane caveolae and a regulator of cellular processes, is
associated with colorectal cancer (CRC), its involvement in the disease
progression is largely unknown. This study aimed to explore the role of Cav-1 in
CRC and the associated mechanisms. MATERIAL AND METHODS Fresh tissues from
patients with CRC and human CRC SW480 cells were used to evaluate Cav-1 and Ki-67
expression using immunohistochemistry and Western blotting. The MTS and Transwell
assays were performed to determine the effects of Cav-1 overexpression via
pcDNA3.1/Cav-1 plasmid on cell proliferation and metastasis. The effect of Cav-1
on the epidermal growth factor receptor (EGFR) activation was evaluated by
Western blotting. The correlation of Cav-1 expression with clinicopathological
factors was statistically analyzed. RESULTS Overexpression of Cav-1 significantly
reduced proliferation, migration, and invasion of SW480 cancer cells in vitro.
The EGF-induced phosphorylation of EGFR and activations of the RAF-MEK-ERK and
PI3K-AKT pathways were adversely regulated by Cav-1 overexpression in vitro. In
76 cases of CRC patients with EGFR expression, a negative correlation was
observed between the level of Cav-1 and tumor-node-metastasis stage, lymph node
metastasis, and distant metastasis (All p<0.05). Finally, the expression level of
Cav-1 was negatively correlated with that of Ki-67. CONCLUSIONS This report is
the first to show that overexpression of Cav-1significantly inhibits the
proliferation, migration, and invasion potential of SW480 cells, possibly through
reducing EGF-induced EGFR activation. High Cav-1 expression level may be a
predictor of positive outcomes in patients with colorectal cancer.
PMID- 29339716
TI - To Explore the Mechanism of the GRM4 Gene in Osteosarcoma by RNA Sequencing and
Bioinformatics Approach.
AB - BACKGROUND Glutamate metabotropic receptor 4 (GRM4) has been correlated with the
pathogenesis of osteosarcoma. The objective of this study was to explore the
underlying molecular mechanism of GRM4 in osteosarcoma. MATERIAL AND METHODS The
expression levels of GRM4 in four human osteosarcoma cell lines and hFOB1.19
cells were examined by real-time quantitative PCR (RT-qPCR). The U2OS cells of
the highest GRM4 expression were transfected with lentivirus-mediated small
interfering RNA (siRNA). The differentially expressed genes (DEGs) after GRM4
gene silencing were screened through RNA sequencing, and analyzed by
bioinformatics. Additionally, the transcription factors (TFs) targeting GRM4 were
predicted and the downstream protein-protein interaction (PPI) network was
constructed using the bioinformatics approach. RESULTS A total of 51 significant
DEGs were obtained, including 14 upregulated and 37 downregulated DEGs. The Kyoto
Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEGs
indicated that four significant enrichment pathways were obtained. A total of six
TFs that could be involved in the transcriptional regulation of GRM4 were
detected. The results showed that 182 genes in the PPI network were significantly
enriched in 14 pathways. The chemokines and chemokine receptors were found to be
significantly enriched in three pathways. CONCLUSIONS The DEGs in the four
significant enrichment pathways might participate in the development and
progression of osteosarcoma through GRM4. The results revealed that EGR1 and CTCF
are probably involved in the transcriptional regulation of GRM4, which
participates in the progress of osteosarcoma by interacting with chemokines and
their receptors.
PMID- 29339717
TI - Complex Reconstruction with Flaps After Abdominoperineal Resection and Groin
Dissection for Anal Squamous Cell Carcinoma: A Difficult Case Involving Many
Specialities.
AB - BACKGROUND Anal squamous cell carcinoma accounts for about 2-4% of all lower
gastrointestinal malignancies, with a distant disease reported in less than 5%.
Although surgical treatment is rarely necessary, this often involve large
dissections and difficult reconstructive procedures. CASE REPORT We present a
complex but successful case of double-flap reconstruction after abdominoperineal
resection and groin dissection for anal squamous cell carcinoma (cT3N3M0) with
metastatic right inguinal lymph nodes and ipsilateral threatening of femoral
vessels. A multi-specialty team was involved in the operation. A vascular and
plastic surgeon performed the inguinal dissection with en bloc excision of the
saphenous magna and a cuff of the femoral vein, while colorectal surgeons carried
out the abdominoperineal excision. The 2 large tissue gaps at the groin and
perineum were covered with an oblique rectus abdominis myocutaneous flap and a
gluteal lotus flap, respectively. A partially absorbable mesh was placed at the
level of the anterior sheath in order to reinforce the abdominal wall, whereas an
absorbable mesh was used as a bridge for the dissected pelvic floor muscles. The
post-operative period was uneventful and the follow-up at 5 months showed good
results. CONCLUSIONS An early diagnosis along with new techniques of
radiochemotherapy allow patients to preserve their sphincter function. However, a
persistent or recurrent disease needs major operations, which often involve a
complex reconstruction. Good team-work and experience in specialized fields give
the opportunity to make the best choices to perform critical steps during the
management of complex cases.
PMID- 29339718
TI - Injury-activated glial cells promote wound healing of the adult skin in mice.
AB - Cutaneous wound healing is a complex process that aims to re-establish the
original structure of the skin and its functions. Among other disorders,
peripheral neuropathies are known to severely impair wound healing capabilities
of the skin, revealing the importance of skin innervation for proper repair.
Here, we report that peripheral glia are crucially involved in this process.
Using a mouse model of wound healing, combined with in vivo fate mapping, we show
that injury activates peripheral glia by promoting de-differentiation, cell-cycle
re-entry and dissemination of the cells into the wound bed. Moreover, injury
activated glia upregulate the expression of many secreted factors previously
associated with wound healing and promote myofibroblast differentiation by
paracrine modulation of TGF-beta signalling. Accordingly, depletion of these
cells impairs epithelial proliferation and wound closure through contraction,
while their expansion promotes myofibroblast formation. Thus, injury-activated
glia and/or their secretome might have therapeutic potential in human wound
healing disorders.
PMID- 29339719
TI - miR-181a-5p suppresses invasion and migration of HTR-8/SVneo cells by directly
targeting IGF2BP2.
AB - Pre-eclampsia is a pregnancy-related disease that may cause maternal, neonatal
and fetal morbidity and mortality and exists in 3-5% of pregnancies worldwide.
The discovery of dysregulated microRNAs and their roles in placental development
has provided a new avenue for elucidating the mechanism involved in this
pregnancy-specific disorder. Here, the roles of human miR-181a-5p, a microRNA
that is increased in both the plasma and placenta of severe pre-eclamptic
patients, in invasion and migration of trophoblasts were investigated. Ectopic
expression of miR-181a-5p impaired the invasion and migration of HTR-8/SVneo
cells, whereas miR-181a-5p inhibition had the opposite effects. IGF2BP2, which
harbors a highly conserved miR-181a-5p-binding site within its 3'-UTR, was
identified to be directly inhibited by miR-181a-5p. Moreover, siRNAs targeting
IGF2BP2 imitated the effects of overexpressed miR-181a-5p on HTR-8/SVneo cell
invasion and migration, whereas restoring IGF2BP2 expression by overexpressing a
plasmid encoding IGF2BP2 partially reversed the studied inhibitory functions of
miR-181a-5p. Thus, we demonstrated here that miR-181a-5p suppresses the invasion
and migration of cytotrophoblasts, and its inhibitory effects were at least
partially mediated by the suppression of IGF2BP2 expression, thus shedding new
light on the roles of miR-181a-5p in the pathogenesis of severe pre-eclampsia.
PMID- 29339720
TI - Plumbagin inhibits the proliferation and survival of esophageal cancer cells by
blocking STAT3-PLK1-AKT signaling.
AB - Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers, and it
requires novel treatment approaches and effective drugs. In the present study, we
found that treatment with plumbagin, a natural compound, reduced proliferation
and survival of the KYSE150 and KYSE450 ESCC cell lines in a dose-dependent
manner in vitro. The drug also effectively inhibited the viability of primary
ESCC cells from fresh biopsy specimens. Furthermore, plumbagin-induced mitotic
arrest and massive apoptosis in ESCC cells. Notably, the drug significantly
suppressed the colony formation capacity of ESCC cells in vitro and the growth of
KYSE150 xenograft tumors in vivo. At the molecular level, we found that exposure
to plumbagin decreased both polo-like kinase 1 (PLK1) and phosphorylated protein
kinase B (p-AKT) expression in both ESCC cell lines. Enforced PLK1 expression in
ESCC cells not only markedly rescued cells from plumbagin-induced apoptosis and
proliferation inhibition but also restored the impaired AKT activity.
Furthermore, signal transducer and activator of transcription 3 (STAT3), a
transcription factor of PLK1, was also inactivated in plumbagin-treated ESCC
cells; however, the overexpression of a constitutively activated STAT3 mutant,
STAT3C, reinstated the plumbagin-elicited blockade of PLK1-AKT signaling in ESCC
cells. Taken together, these findings indicate that plumbagin inhibits
proliferation and potentiates apoptosis in human ESCC cells in vitro and in vivo.
Plumbagin may exert these antitumor effects by abrogating STAT3-PLK1-AKT
signaling, which suggests that plumbagin may be a novel, promising anticancer
agent for the treatment of ESCC.
PMID- 29339721
TI - Single-molecule FRET reveals multiscale chromatin dynamics modulated by HP1alpha.
AB - The dynamic architecture of chromatin fibers, a key determinant of genome
regulation, is poorly understood. Here, we employ multimodal single-molecule
Forster resonance energy transfer studies to reveal structural states and their
interconversion kinetics in chromatin fibers. We show that nucleosomes engage in
short-lived (micro- to milliseconds) stacking interactions with one of their
neighbors. This results in discrete tetranucleosome units with distinct
interaction registers that interconvert within hundreds of milliseconds.
Additionally, we find that dynamic chromatin architecture is modulated by the
multivalent architectural protein heterochromatin protein 1alpha (HP1alpha),
which engages methylated histone tails and thereby transiently stabilizes stacked
nucleosomes. This compacted state nevertheless remains dynamic, exhibiting
fluctuations on the timescale of HP1alpha residence times. Overall, this study
reveals that exposure of internal DNA sites and nucleosome surfaces in chromatin
fibers is governed by an intrinsic dynamic hierarchy from micro- to milliseconds,
allowing the gene regulation machinery to access compact chromatin.
PMID- 29339722
TI - The deep-subsurface sulfate reducer Desulfotomaculum kuznetsovii employs two
methanol-degrading pathways.
AB - Methanol is generally metabolized through a pathway initiated by a cobalamine
containing methanol methyltransferase by anaerobic methylotrophs (such as
methanogens and acetogens), or through oxidation to formaldehyde using a methanol
dehydrogenase by aerobes. Methanol is an important substrate in deep-subsurface
environments, where thermophilic sulfate-reducing bacteria of the genus
Desulfotomaculum have key roles. Here, we study the methanol metabolism of
Desulfotomaculum kuznetsovii strain 17T, isolated from a 3000-m deep geothermal
water reservoir. We use proteomics to analyze cells grown with methanol and
sulfate in the presence and absence of cobalt and vitamin B12. The results
indicate the presence of two methanol-degrading pathways in D. kuznetsovii, a
cobalt-dependent methanol methyltransferase and a cobalt-independent methanol
dehydrogenase, which is further confirmed by stable isotope fractionation. This
is the first report of a microorganism utilizing two distinct methanol conversion
pathways. We hypothesize that this gives D. kuznetsovii a competitive advantage
in its natural environment.
PMID- 29339723
TI - Fasoracetam in adolescents with ADHD and glutamatergic gene network variants
disrupting mGluR neurotransmitter signaling.
AB - The glutamatergic neurotransmitter system may play an important role in attention
deficit hyperactivity disorder (ADHD). This 5-week, open-label, single-blind,
placebo-controlled study reports the safety, pharmacokinetics and responsiveness
of the metabotropic glutamate receptor (mGluR) activator fasoracetam (NFC-1), in
30 adolescents, age 12-17 years with ADHD, harboring mutations in mGluR network
genes. Mutation status was double-blinded. A single-dose pharmacokinetic
profiling from 50-800 mg was followed by a single-blind placebo at week 1 and
subsequent symptom-driven dose advancement up to 400 mg BID for 4 weeks. NFC-1
treatment resulted in significant improvement. Mean Clinical Global Impressions
Improvement (CGI-I) and Severity (CGI-S) scores were, respectively, 3.79 at
baseline vs. 2.33 at week 5 (P < 0.001) and 4.83 at baseline vs. 3.86 at week 5
(P < 0.001). Parental Vanderbilt scores showed significant improvement for
subjects with mGluR Tier 1 variants (P < 0.035). There were no differences in the
incidence of adverse events between placebo week and weeks on active drug. The
trial is registered at https://clinicaltrials.gov/ct2/show/study/NCT02286817 .
PMID- 29339724
TI - Granulocyte-colony stimulating factor controls neural and behavioral plasticity
in response to cocaine.
AB - Cocaine addiction is characterized by dysfunction in reward-related brain
circuits, leading to maladaptive motivation to seek and take the drug. There are
currently no clinically available pharmacotherapies to treat cocaine addiction.
Through a broad screen of innate immune mediators, we identify granulocyte-colony
stimulating factor (G-CSF) as a potent mediator of cocaine-induced adaptations.
Here we report that G-CSF potentiates cocaine-induced increases in neural
activity in the nucleus accumbens (NAc) and prefrontal cortex. In addition, G-CSF
injections potentiate cocaine place preference and enhance motivation to self
administer cocaine, while not affecting responses to natural rewards. Infusion of
G-CSF neutralizing antibody into NAc blocks the ability of G-CSF to modulate
cocaine's behavioral effects, providing a direct link between central G-CSF
action in NAc and cocaine reward. These results demonstrate that manipulating G
CSF is sufficient to alter the motivation for cocaine, but not natural rewards,
providing a pharmacotherapeutic avenue to manipulate addictive behaviors without
abuse potential.
PMID- 29339725
TI - TGR5 signalling promotes mitochondrial fission and beige remodelling of white
adipose tissue.
AB - Remodelling of energy storing white fat into energy expending beige fat could be
a promising strategy to reduce adiposity. Here, we show that the bile acid
responsive membrane receptor TGR5 mediates beiging of the subcutaneous white
adipose tissue (scWAT) under multiple environmental cues including cold exposure
and prolonged high-fat diet feeding. Moreover, administration of TGR5-selective
bile acid mimetics to thermoneutral housed mice leads to the appearance of beige
adipocyte markers and increases mitochondrial content in the scWAT of Tgr5 +/+
mice but not in their Tgr5 -/- littermates. This phenotype is recapitulated in
vitro in differentiated adipocytes, in which TGR5 activation increases free fatty
acid availability through lipolysis, hence fuelling beta-oxidation and
thermogenic activity. TGR5 signalling also induces mitochondrial fission through
the ERK/DRP1 pathway, further improving mitochondrial respiration. Taken
together, these data identify TGR5 as a druggable target to promote beiging with
potential applications in the management of metabolic disorders.
PMID- 29339726
TI - Publisher Correction: Identification and characterization of two functional
variants in the human longevity gene FOXO3.
AB - The original version of this Article contained an error in the spelling of the
author Robert Hasler, which was incorrectly given as Robert Haesler. This has now
been corrected in both the PDF and HTML versions of the Article.
PMID- 29339727
TI - Analysis of criteria for treatment initiation in patients with progressive
chronic lymphocytic leukemia.
PMID- 29339728
TI - How BMP-2 induces EMT and breast cancer stemness through Rb and CD44?
PMID- 29339729
TI - Ecotropic viral integration site 1 promotes metastasis independent of epithelial
mesenchymal transition in colon cancer cells.
AB - The most indecipherable component of solid cancer is the development of
metastasis which accounts for more than 90% of cancer-related mortalities. A
developmental program termed epithelial-mesenchymal transition (EMT) has also
been shown to play a critical role in promoting metastasis in epithelium-derived
solid tumors. By analyzing publicly available microarray datasets, we observed
that ecotropic viral integration site 1 (EVI1) correlates negatively with SLUG, a
master regulator of EMT. This correlation was found to be relevant as we
demonstrated that EVI1 binds to SLUG promoter element directly through the distal
set of zinc fingers and downregulates its expression. Many studies have shown
that the primary role of SLUG during EMT and EMT-like processes is the regulation
of cell motility in most of the cancer cells. Knockdown of EVI1 in metastatic
colon cancer cell and subsequent passage through matrigel not only increased the
invading capacity but also induced an EMT-like morphological feature of the
cells, such as spindle-shaped appearance and led to a significant reduction in
the expression of the epithelial marker, E-CADHERIN and increase in the
expression of the mesenchymal marker, N-CADHERIN. The cells, when injected into
immunocompromised mice, failed to show any metastatic foci in distant organs
however the ones with EVI1, metastasized in the intraperitoneal layer and also
showed multiple micro metastatic foci in the lungs and spleen. These findings
suggest that in colon cancer EVI1 is dispensable for epithelial-mesenchymal
transition, however, is required for metastasis.
PMID- 29339730
TI - Mutational heterogeneity of angioimmunoblastic T-cell lymphoma indicates distinct
lymphomagenic pathways.
PMID- 29339731
TI - Electron affinity of liquid water.
AB - Understanding redox and photochemical reactions in aqueous environments requires
a precise knowledge of the ionization potential and electron affinity of liquid
water. The former has been measured, but not the latter. We predict the electron
affinity of liquid water and of its surface from first principles, coupling path
integral molecular dynamics with ab initio potentials, and many-body perturbation
theory. Our results for the surface (0.8 eV) agree well with recent pump-probe
spectroscopy measurements on amorphous ice. Those for the bulk (0.1-0.3 eV)
differ from several estimates adopted in the literature, which we critically
revisit. We show that the ionization potential of the bulk and surface are almost
identical; instead their electron affinities differ substantially, with the
conduction band edge of the surface much deeper in energy than that of the bulk.
We also discuss the significant impact of nuclear quantum effects on the
fundamental gap and band edges of the liquid.
PMID- 29339732
TI - Glyburide and retinoic acid synergize to promote wound healing by anti
inflammation and RIP140 degradation.
AB - Chronic inflammation underlies the development of metabolic diseases and
individuals with metabolic disease often also suffer from delayed wound healing
due to prolonged inflammation. Resolving inflammation provides a therapeutic
strategy in treating metabolic diseases. We previously showed that during an anti
inflammatory response when macrophages were alternatively (M2) polarized,
retinoic acid (RA) dramatically activated arginase 1 gene (Arg1), a gene crucial
for wound healing. Here we report that a widely used sulfonylurea drug for type 2
diabetes mellitus (T2DM), glyburide, enhances the anti-inflammatory response and
synergizes with RA to promote wound healing. Our data also delineate the
mechanism underlying glyburide's anti-inflammatory effect, which is to stimulate
the degradation of a pro-inflammatory regulator, Receptor Interacting Protein 140
(RIP140), by activating Ca2+/calmodulin-dependent protein kinase II (CamKII) that
triggers specific ubiquitination of RIP140 for degradation. By stimulating RIP140
degradation, glyburide enhances M2 polarization and anti-inflammation. Using a
high-fat diet induced obesity mouse model to monitor wound healing effects, we
provide a proof-of-concept for a therapeutic strategy that combining glyburide
and RA can significantly improve wound healing. Mechanistically, this study
uncovers a new mechanism of action of glyburide and a new pathway modulating
RIP140 protein degradation that is mediated by CamKII signaling.
PMID- 29339733
TI - Role of Macromolecular Crowding on the Intracellular Diffusion of DNA Binding
Proteins.
AB - Recent experiments suggest that cellular crowding facilitates the target search
dynamics of proteins on DNA, the mechanism of which is not yet known. By using
large scale computer simulations, we show that two competing factors, namely the
width of the depletion layer that separates the crowder cloud from the DNA
molecule and the degree of protein-crowder crosstalk, act in harmony to affect
the target search dynamics of proteins. The impacts vary from nonspecific to
specific target search regime. During a nonspecific search, dynamics of a protein
is only minimally affected, whereas, a significantly different behaviour is
observed when the protein starts forming a specific protein-DNA complex. We also
find that the severity of impacts largely depends upon physiological crowder
concentration and deviation from it leads to attenuation in the binding kinetics.
Based on extensive kinetic study and binding energy landscape analysis, we
further present a comprehensive molecular description of the search process that
allows us to interpret the experimental findings.
PMID- 29339734
TI - Au@Nb@H x K1-xNbO3 nanopeapods with near-infrared active plasmonic hot-electron
injection for water splitting.
AB - Full-spectrum utilization of diffusive solar energy by a photocatalyst for
environmental remediation and fuel generation has long been pursued. In contrast
to tremendous efforts in the UV-to-VIS light regime of the solar spectrum, the
NIR and IR areas have been barely addressed although they represent about 50% of
the solar flux. Here we put forward a biomimetic photocatalyst blueprint that
emulates the growth pattern of a natural plant-a peapod-to address this issue.
This design is exemplified via unidirectionally seeding core-shell Au@Nb
nanoparticles in the cavity of semiconducting H x K1-xNbO3 nanoscrolls. The
biomimicry of this nanopeapod (NPP) configuration promotes near-field plasmon
plasmon coupling between bimetallic Au@Nb nanoantennas (the peas), endowing the
UV-active H x K1-xNbO3 semiconductor (the pods) with strong VIS and NIR light
harvesting abilities. Moreover, the characteristic 3D metal-semiconductor
junction of the Au@Nb@H x K1-xNbO3 NPPs favors the transfer of plasmonic hot
carriers to trigger dye photodegradation and water photoelectrolysis as proofs-of
concept. Such broadband solar spectral response renders the Au@Nb@H x K1-xNbO3
NPPs highly promising for widespread photoactive devices.
PMID- 29339735
TI - Phenotype and Functional Features of Human Telomerase Reverse Transcriptase
Immortalized Human Airway Smooth Muscle Cells from Asthmatic and Non-Asthmatic
Donors.
AB - Asthma is an obstructive respiratory disease characterised by chronic
inflammation with airway hyperresponsiveness. In asthmatic airways, there is an
increase in airway smooth muscle (ASM) cell bulk, which differs from non
asthmatic ASM in characteristics. This study aimed to assess the usefulness of
hTERT immortalisation of human ASM cells as a research tool. Specifically we
compared proliferative capacity, inflammatory mediator release and extracellular
matrix (ECM) production in hTERT immortalised and parent primary ASM cells from
asthmatic and non-asthmatic donors. Our studies revealed no significant
differences in proliferation, IL-6 and eotaxin-1 production, or CTGF synthesis
between donor-matched parent and hTERT immortalised ASM cell lines. However,
deposition of ECM proteins fibronectin and fibulin-1 was significantly lower in
immortalised ASM cells compared to corresponding primary cells. Notably,
previously reported differences in proliferation and inflammatory mediator
release between asthmatic and non-asthmatic ASM cells were retained, but
excessive ECM protein deposition in asthmatic ASM cells was lost in hTERT ASM
cells. This study shows that hTERT immortalised ASM cells mirror primary ASM
cells in proliferation and inflammatory profile characteristics. Moreover, we
demonstrate both strengths and weaknesses of this immortalised cell model as a
representation of primary ASM cells for future asthma pathophysiological
research.
PMID- 29339736
TI - Groups clapping in unison undergo size-dependent error-induced frequency
increase.
AB - Humans clapping together in unison is a familiar and robust example of emergent
synchrony. We find that in experiments, such groups (from two to a few hundred)
always increase clapping frequency, and larger groups increase more quickly.
Based on single-person experiments and modeling, an individual tendency to rush
is ruled out as an explanation. Instead, an asymmetric sensitivity in aural
interactions explains the frequency increase, whereby individuals correct more
strongly to match neighbour claps that precede their own clap, than those that
follow it. A simple conceptual coupled oscillator model based on this interaction
recovers the main features observed in experiments, and shows that the collective
frequency increase is driven by the small timing errors in individuals, and the
resulting inter-individual interactions that occur to maintain unison.
PMID- 29339737
TI - Breakdown of Kasha's Rule in a Ubiquitous, Naturally Occurring, Wide Bandgap
Aluminosilicate (Feldspar).
AB - Excitation-energy-dependent emission (EDE) is well known from photoluminescence
(PL) studies of polar solvents and carbon-based nanostructures. In polar
solvents, this effect known as the 'red edge effect' (REE) is understood to arise
from solute-solvent interactions, whereas, in case of carbon-based
nanostructures, the origin is highly debated. Understanding this effect has
important bearings on the potential applications of these materials. EDE has
never been reported from large crystalline materials, except very recently by our
group. Here, we make detailed investigations to understand the universality and
the mechanism behind the EDE in a wide band gap aluminosilicate (feldspar), which
comprises more than half of the Earth's crust, and is widely used in geophotonics
(e.g., optical dating). We observe EDE up to 150 nm at room temperature in our
samples, which is unprecedented in rigid macroscopic structures. Based on PL
investigations at 295 K and 7 K, we present a novel model that is based on
photoionisation of a deep lying defect and subsequent transport/relaxation of
free electrons in the sub-conduction band tail states. Our model has important
implications for potential photonic applications using feldspar, measurement of
band tail width in wide bandgap materials, and understanding the EDE effect in
other materials.
PMID- 29339738
TI - DNA methyltransferase inhibition upregulates MHC-I to potentiate cytotoxic T
lymphocyte responses in breast cancer.
AB - Potentiating anti-tumor immunity by inducing tumor inflammation and T cell
mediated responses are a promising area of cancer therapy. Immunomodulatory
agents that promote these effects function via a wide variety of mechanisms,
including upregulation of antigen presentation pathways. Here, we show that major
histocompatibility class-I (MHC-I) genes are methylated in human breast cancers,
suppressing their expression. Treatment of breast cancer cell lines with a next
generation hypomethylating agent, guadecitabine, upregulates MHC-I expression in
response to interferon-gamma. In murine tumor models of breast cancer,
guadecitabine upregulates MHC-I in tumor cells promoting recruitment of CD8+ T
cells to the microenvironment. Finally, we show that MHC-I genes are upregulated
in breast cancer patients treated with hypomethylating agents. Thus, the
immunomodulatory effects of hypomethylating agents likely involve upregulation of
class-I antigen presentation to potentiate CD8+ T cell responses. These
strategies may be useful to potentiate anti-tumor immunity and responses to
checkpoint inhibition in immune-refractory breast cancers.
PMID- 29339740
TI - Understanding turbulent free-surface vortex flows using a Taylor-Couette flow
analogy.
AB - Free-surface vortices have long been studied to develop an understanding of
similar rotating flow phenomena observed in nature and technology. However, a
complete description of its turbulent three-dimensional flow field still remains
elusive. In contrast, the related Taylor-Couette flow system has been well
explicated which classically exhibits successive instability phases manifested in
so-called Taylor vortices. In this study, observations made on the turbulent free
surface vortex revealed distinguishable, time-dependent "Taylor-like" vortices in
the secondary flow field similar to the Taylor-Couette flow system. The
observations were enabled by an original application of 2D ultrasonic Doppler
velocity profiling complemented with laser induced fluorescence dye observations.
Additional confirmation was provided by three-dimensional numerical simulations.
Using Rayleigh's stability criterion, we analytically show that a wall bounded
free-surface vortex can indeed become unstable due to a centrifugal driving force
in a similar manner to the Taylor-Couette flow. Consequently, it is proposed that
the free-surface vortex can be treated analogously to the Taylor-Couette flow
permitting advanced conclusions to be drawn on its flow structure and the various
states of free-surface vortex flow stability.
PMID- 29339739
TI - Newborn screening of glucose-6-phosphate dehydrogenase deficiency in Guangxi,
China: determination of optimal cutoff value to identify heterozygous female
neonates.
AB - The aim of this study is to assess the disease incidence and mutation spectrum of
glucose-6-phosphate dehydrogenase (G6PD) deficiency in Guangxi, China, and to
determine an optimal cutoff value to identify heterozygous female neonates. A
total of 130, 635 neonates were screened from the year of 2013 to 2017. Neonates
suspected for G6PD deficiency were further analyzed by quantitatively enzymatic
assay and G6PD mutation analysis. The overall incidence of G6PD deficiency was
7.28%. A total of 14 G6PD mutations were identified, and different mutations lead
to varying levels of G6PD enzymatic activities. The best cut-off value of G6PD
activity in male subjects is 2.2 U/g Hb, same as conventional setting. In female
population, however, the cut-off value is found to be 2.8 U/g Hb (sensitivity:
97.5%, specificity: 87.7%, AUC: 0.964) to best discriminate between normal and
heterozygotes, and 1.6 U/g Hb (sensitivity: 82.2%, specificity: 85.9%, AUC:
0.871) between heterozygotes and deficient subjects. In conclusion, we have
conducted a comprehensive newborn screening of G6PD deficiency in a large cohort
of population from Guangxi, China, and first established a reliable cut-off value
of G6PD activity to distinguish heterozygous females from either normal or
deficient subjects.
PMID- 29339741
TI - Mesoscale Dzyaloshinskii-Moriya interaction: geometrical tailoring of the
magnetochirality.
AB - Crystals with broken inversion symmetry can host fundamentally appealing and
technologically relevant periodical or localized chiral magnetic textures. The
type of the texture as well as its magnetochiral properties are determined by the
intrinsic Dzyaloshinskii-Moriya interaction (DMI), which is a material property
and can hardly be changed. Here we put forth a method to create new artificial
chiral nanoscale objects with tunable magnetochiral properties from standard
magnetic materials by using geometrical manipulations. We introduce a mesoscale
Dzyaloshinskii-Moriya interaction that combines the intrinsic spin-orbit and
extrinsic curvature-driven DMI terms and depends both on the material and
geometrical parameters. The vector of the mesoscale DMI determines magnetochiral
properties of any curved magnetic system with broken inversion symmetry. The
strength and orientation of this vector can be changed by properly choosing the
geometry. For a specific example of nanosized magnetic helix, the same material
system with different geometrical parameters can acquire one of three zero
temperature magnetic phases, namely, phase with a quasitangential magnetization
state, phase with a periodical state and one intermediate phase with a periodical
domain wall state. Our approach paves the way towards the realization of a new
class of nanoscale spintronic and spinorbitronic devices with the geometrically
tunable magnetochirality.
PMID- 29339742
TI - SLAF-based high-density genetic map construction and QTL mapping for major
economic traits in sea urchin Strongylocentrotus intermedius.
AB - Sea urchin (Strongylocentrotus intermedius) has long been a model species for
developmental and evolutionary research, but only a few studies have focused on
gene mapping. Here, we reported a high-density genetic map containing 4,387
polymorphism specific-length amplified fragment (SLAF) markers spanning 21
linkage groups (LG) for sea urchin. Based on this genetic map and phenotyping
data for eight economic traits, 33 potentially significant QTLs were detected on
ten different LGs with explanations ranging from 9.90% to 46.30%, partly
including 10 QTLs for test diameter, six QTLs for body weight and eight QTLs for
Aristotle's lantern weight. Moreover, we found a QTL enrichment LG, LG15,
gathering QTLs for test diameter, body weight, gonad weight, light orange-yellow
color difference (>=E1) and light yellow color difference (>=E2). Among all QTLs,
we genotyped four QTLs for test diameter, Aristotle's lantern weight and body
weight using High Resolution Melting (HRM) technology. Finally, we used the
verified SNP marker (detected using SLAF sequencing) to explore their marker
assisted selection (MAS) breeding application potential and found that SNP-29
associated tightly with body weight and that heterozygous genotype was a dominant
genotype, indicating that SNP-29 was a promising marker for MAS.
PMID- 29339743
TI - A deep study of the protection of Lithium Cobalt Oxide with polymer surface
modification at 4.5 V high voltage.
AB - Charging the cells above a conventional voltage of 4.2 V is a promising attempt
to increase the energy density of Lithium Cobalt Oxide (LCO), however, the
problem of crystal instability at high voltage that leading deterioration of
cycle performance needs to be urgently resolved. In this work, as an effective
and easy approach to improve the cycle performance and crystal stability of LCO
cycling at 4.5 V high voltage, we demonstrate direct surface modification of a
LCO cathode by poly [N,N-bis(2-cryano-ethyl)-acrylamide]. The results of SEM, TEM
and XRD all indicate that the crystal structure of polymer coating LCO remains
unchanged after cycling at 4.5 V high voltage for 60 times. Furthermore, the XPS
study of valence of cobalt on the surface of LCO demonstrates that cobaltic ion
of polymer coating LCO can be reduced to cobaltous ion after charging the cell.
Thus, the activity of the crystal surface can be weakened, as a result, the
stability is improved, leading to the performance improvement.
PMID- 29339744
TI - Human caspase-4 detects tetra-acylated LPS and cytosolic Francisella and
functions differently from murine caspase-11.
AB - Caspase-4/5 in humans and caspase-11 in mice bind hexa-acylated lipid A, the
lipid moeity of lipopolysaccharide (LPS), to induce the activation of non
canonical inflammasome. Pathogens such as Francisella novicida express an under
acylated lipid A and escape caspase-11 recognition in mice. Here, we show that
caspase-4 drives inflammasome responses to F. novicida infection in human
macrophages. Caspase-4 triggers F. novicida-mediated, gasdermin D-dependent
pyroptosis and activates the NLRP3 inflammasome. Inflammasome activation could be
recapitulated by transfection of under-acylated LPS from different bacterial
species or synthetic tetra-acylated lipid A into cytosol of human macrophage. Our
results indicate functional differences between human caspase-4 and murine
caspase-11. We further establish that human Guanylate-binding proteins promote
inflammasome responses to under-acylated LPS. Altogether, our data demonstrate a
broader reactivity of caspase-4 to under-acylated LPS than caspase-11, which may
have important clinical implications for management of sepsis.
PMID- 29339746
TI - Zika Virus in Salivary Glands of Five Different Species of Wild-Caught Mosquitoes
from Mexico.
AB - Zika virus (ZIKV) is a mosquito-borne pathogen, and Aedes aegypti has been
identified as the main vector of the disease. Other mosquito species in the Aedes
and Culex genera have been suggested to have the potential for being competent
vectors based on experimental exposition of mosquitoes to an infectious blood
meal containing ZIKV. Here, we report the isolation in cell culture of ZIKV
obtained from different body parts of wild-caught female mosquitoes (Ae. aegypti,
Ae. vexans, Cx. quinquefasciatus, Cx. coronator, and Cx. tarsalis) and whole male
mosquitoes (Ae. aegypti and Cx. quinquefasciatus) in Mexico. Importantly, this is
the first report that shows the presence of the virus in the salivary glands of
the wild-caught female mosquitoes species, Cx. coronator, Cx. tarsalis, and Ae.
vexans. Our findings strongly suggest that all the species reported herein are
potential vectors for ZIKV.
PMID- 29339745
TI - Genomic and transcriptomic analysis of the Asian honeybee Apis cerana provides
novel insights into honeybee biology.
AB - The Asian honeybee Apis cerana is one of two bee species that have been
commercially kept with immense economic value. Here we present the analysis of
genomic sequence and transcriptomic exploration for A. cerana as well as the
comparative genomic analysis of the Asian honeybee and the European honeybee A.
mellifera. The genome and RNA-seq data yield new insights into the behavioral and
physiological resistance to the parasitic mite Varroa the evolution of
antimicrobial peptides, and the genetic basis for labor division in A. cerana.
Comparison of genes between the two sister species revealed genes specific to A.
cerana, 54.5% of which have no homology to any known proteins. The observation
that A. cerana displayed significantly more vigilant grooming behaviors to the
presence of Varroa than A. mellifera in conjunction with gene expression analysis
suggests that parasite-defensive grooming in A. cerana is likely triggered not
only by exogenous stimuli through visual and olfactory detection of the parasite,
but also by genetically endogenous processes that periodically activates a bout
of grooming to remove the ectoparasite. This information provides a valuable
platform to facilitate the traits unique to A. cerana as well as those shared
with other social bees for health improvement.
PMID- 29339747
TI - An orthotopic mouse model of gastric cancer invasion and metastasis.
AB - Gastric cancer is a leading cause of cancer death worldwide, with advanced stage
being correlated to the level of tumour invasion and metastasis. Current research
is heavily focused on the identification and development of efficacious
therapeutics targeting these fundamental hallmarks of cancer, however there are
currently no animal models that mimic the invasive phenotypes observed in humans.
To address this we have developed an orthotopic mouse model whereby gastric
cancer cell lines are tagged with luciferase and injected into the subserosal
layer of the stomach. This allows for the monitoring of primary tumour growth and
metastasis in real-time as well as quantitation of the degree of tumour invasion
through the stomach wall by immunohistochemistry. We have three models based on
the degree of invasion and metastasis that are cell line specific: The AGS cells
develop into invasive tumours by 4-weeks with no evidence of metastases, MKN45
cells are moderately metastatic with minimal invasion till week 2 and MKN28 cells
are highly metastatic and fully invasive by week 1. These models have utility as
a tool for testing the efficacy of anti-tumour, anti-invasive and anti-metastatic
therapies in the setting of gastric cancer, which currently has poor treatment
options.
PMID- 29339748
TI - Dot1 regulates nucleosome dynamics by its inherent histone chaperone activity in
yeast.
AB - Dot1 (disruptor of telomeric silencing-1, DOT1L in humans) is the only known
enzyme responsible for histone H3 lysine 79 methylation (H3K79me) and is
evolutionarily conserved in most eukaryotes. Yeast Dot1p lacks a SET domain and
does not methylate free histones and thus may have different actions with respect
to other histone methyltransferases. Here we show that Dot1p displays histone
chaperone activity and regulates nucleosome dynamics via histone exchange in
yeast. We show that a methylation-independent function of Dot1p is required for
the cryptic transcription within transcribed regions seen following disruption of
the Set2-Rpd3S pathway. Dot1p can assemble core histones to nucleosomes and
facilitate ATP-dependent chromatin-remodeling activity through its nucleosome
binding domain, in vitro. Global analysis indicates that Dot1p appears to be
particularly important for histone exchange and chromatin accessibility on the
transcribed regions of long-length genes. Our findings collectively suggest that
Dot1p-mediated histone chaperone activity controls nucleosome dynamics in
transcribed regions.
PMID- 29339749
TI - Volatile molecules from bronchoalveolar lavage fluid can 'rule-in' Pseudomonas
aeruginosa and 'rule-out' Staphylococcus aureus infections in cystic fibrosis
patients.
AB - Respiratory infections caused by Pseudomonas aeruginosa and Staphylococcus aureus
are the leading cause of morbidity and mortality in cystic fibrosis (CF)
patients. The authors aimed to identify volatile biomarkers from bronchoalveolar
lavage (BAL) samples that can guide breath biomarker development for pathogen
identification. BAL samples (n = 154) from CF patients were analyzed using two
dimensional gas chromatography time-of-flight mass spectrometry. Random Forest
was used to select suites of volatiles for identifying P. aeruginosa-positive and
S. aureus-positive samples using multiple infection scenarios and validated using
test sets. Using nine volatile molecules, we differentiated P. aeruginosa
positive (n = 7) from P. aeruginosa-negative (n = 53) samples with an area under
the receiver operating characteristic curve (AUROC) of 0.86 (95% CI 0.71-1.00)
and with positive and negative predictive values of 0.67 (95% CI 0.38-0.75) and
0.92 (95% CI 0.88-1.00), respectively. We were also able to discriminate S.
aureus-positive (n = 15) from S. aureus-negative (n = 45) samples with an AUROC
of 0.88 (95% CI 0.79-1.00) using eight volatiles and with positive and negative
predictive values of 0.86 (95% CI 0.61-0.96) and 0.70 (95% CI 0.61-0.75),
respectively. Prospective validation of identified biomarkers as screening tools
in patient breath may lead to clinical application.
PMID- 29339750
TI - A Single Dose of Modified Vaccinia Ankara expressing Ebola Virus Like Particles
Protects Nonhuman Primates from Lethal Ebola Virus Challenge.
AB - Ebola virus (EBOV), isolate Makona, was the causative agent of the West African
epidemic devastating predominantly Guinea, Liberia and Sierra Leone from 2013
2016. While several experimental vaccine and treatment approaches have been
accelerated through human clinical trials, there is still no approved
countermeasure available against this disease. Here, we report the construction
and preclinical efficacy testing of a novel recombinant modified vaccinia Ankara
(MVA)-based vaccine expressing the EBOV-Makona glycoprotein GP and matrix protein
VP40 (MVA-EBOV). GP and VP40 form EBOV-like particles and elicit protective
immune responses. In this study, we report 100% protection against lethal EBOV
infection in guinea pigs after prime/boost vaccination with MVA-EBOV.
Furthermore, this MVA-EBOV protected macaques from lethal disease after a single
dose or prime/boost vaccination. The vaccine elicited a variety of antibody
responses to both antigens, including neutralizing antibodies and antibodies with
antibody-dependent cellular cytotoxic activity specific for GP. This is the first
report that a replication-deficient MVA vector can confer full protection against
lethal EBOV challenge after a single dose vaccination in macaques.
PMID- 29339751
TI - JmjC domain proteins modulate circadian behaviors and sleep in Drosophila.
AB - Jumonji (JmjC) domain proteins are known regulators of gene expression and
chromatin organization by way of histone demethylation. Chromatin modification
and remodeling provides a means to modulate the activity of large numbers of
genes, but the importance of this class of predicted histone-modifying enzymes
for different aspects of post-developmental processes remains poorly understood.
Here we test the function of all 11 non-lethal members in the regulation of
circadian rhythms and sleep. We find loss of every Drosophila JmjC gene affects
different aspects of circadian behavior and sleep in a specific manner. Together
these findings suggest that the majority of JmjC proteins function as regulators
of behavior, rather than controlling essential developmental programs.
PMID- 29339752
TI - Prognostic Performance of Ten Liver Function Models in Patients with
Hepatocellular Carcinoma Undergoing Radiofrequency Ablation.
AB - Liver functional capacity is a crucial survival determinant for hepatocellular
carcinoma (HCC). Noninvasive models were proposed to assess hepatic reserve, but
their performance in outcome prediction is unclear. We aimed to investigate 10
currently used liver function models in HCC patients undergoing radiofrequency
ablation (RFA). A total 499 HCC patients were prospectively identified.
Homogeneity and corrected Akaike information criteria (AICc) were compared. Cox
proportional hazards model was used to identify independent survival predictors.
Significance survival differences were found across 10 noninvasive models (all p
< 0.001) except for GUCI and APRI grade 2 vs 3, and King's score grade 1 vs 2.
Among these models, ALBI grade showed the highest homogeneity and lowest AICs
value, indicating a better prognostic performance. Within Child-Turcotte-Pugh
(CTP) score 5 group, significant survival difference was demonstrated between
ALBI grade 1 and 2 (p < 0.001); for those with CTP score 6 or higher, only ALBI
grade 2 and 3 showed survival difference (p < 0.001). Cox analysis disclosed that
ALBI grade, tumor size and performance status were independent prognostic
predictors. There was significant correlation between CTP score and other 9
models. We conclude that ALBI grade may serve as objective and feasible surrogate
for prognostic prediction in HCC patients undergoing RFA.
PMID- 29339753
TI - Efficient isolation on Vero.DogSLAMtag cells and full genome characterization of
Dolphin Morbillivirus (DMV) by next generation sequencing.
AB - The Dolphin Morbillivirus (DMV) genome from the first Mediterranean epidemic
(1990-'92) is the only cetacean Morbillivirus that has been completely sequenced.
Here, we report the first application of next generation sequencing (NGS) to
morbillivirus infection of aquatic mammals. A viral isolate, representative of
the 2006-'08 Mediterranean epidemic (DMV_IZSPLV_2008), efficiently grew on
Vero.DogSLAMtag cells and was submitted to whole genome characterization by NGS.
The final genome length was 15,673 nucleotides, covering 99.82% of the DMV
reference genome. Comparison of DMV_IZSPLV_2008 and 1990-'92 DMV strain sequences
revealed 157 nucleotide mutations and 47 amino acid changes. The sequence
similarity was 98.7% at the full genome level. Whole-genome phylogeny suggested
that the DMV strain circulating during the 2006-'08 epidemics emerged from the
1990-'92 DMV strain. Viral isolation is considered the "gold standard" for
morbillivirus diagnostics but efficient propagation of infectious virus is
difficult to achieve. The successful cell replication of this strain allowed
performing NGS directly from the viral RNA, without prior PCR amplification. We
therefore provide to the scientific community a second DMV genome, representative
of another major outbreak. Interestingly, genome comparison revealed that the
neglected L gene encompasses 74% of the genetic diversity and might serve as
"hypervariable" target for strain characterization.
PMID- 29339754
TI - Baicalin modulates NF-kappaB and NLRP3 inflammasome signaling in porcine aortic
vascular endothelial cells Infected by Haemophilus parasuis Causing Glasser's
disease.
AB - Haemophilus parasuis (H. parasuis) can cause vascular inflammatory injury, but
the molecular basis of this effect remains unclear. In this study,we investigated
the effect of the anti-inflammatory, anti-microbial and anti-oxidant agent,
baicalin, on the nuclear factor (NF)-kappaB and NLRP3 inflammasome signaling
pathway in pig primary aortic vascular endothelial cells. Activation of the NF
kappaB and NLRP3 inflammasome signaling pathway was induced in H. parasuis
infected cells. However, baicalin reduced the production of reactive oxygen
species, apoptosis, and activation of the NF-kappaB and NLRP3 inflammasome
signaling pathway in infected cells. These results revealed that baicalin can
inhibit H. parasuis-induced inflammatory responses in porcine aortic vascular
endothelial cells, and may thus offer a novel strategy for controlling and
treating H. parasuis infection. Furthermore, the results suggest that piglet
primary aortic vascular endothelial cells may provide an experimental model for
future studies of H. parasuis infection.
PMID- 29339755
TI - A prebiotic template-directed peptide synthesis based on amyloids.
AB - The prebiotic replication of information-coding molecules is a central problem
concerning life's origins. Here, we report that amyloids composed of short
peptides can direct the sequence-selective, regioselective and stereoselective
condensation of amino acids. The addition of activated DL-arginine and DL
phenylalanine to the peptide RFRFR-NH2 in the presence of the complementary
template peptide Ac-FEFEFEFE-NH2 yields the isotactic product FRFRFRFR-NH2, 1 of
64 possible triple addition products, under conditions in which the absence of
template yields only single and double additions of mixed stereochemistry. The
templating mechanism appears to be general in that a different amyloid formed by
(Orn)V(Orn)V(Orn)V(Orn)V-NH2 and Ac-VDVDVDVDV-NH2 is regioselective and
stereoselective for N-terminal, L-amino-acid addition while the ornithine-valine
peptide alone yields predominantly sidechain condensation products with little
stereoselectivity. Furthermore, the templating reaction is stable over a wide
range of pH (5.6-8.6), salt concentration (0-4 M NaCl), and temperature (25-90
degrees C), making the amyloid an attractive model for a prebiotic peptide
replicating system.
PMID- 29339756
TI - Shot-by-shot characterization of focused X-ray free electron laser pulses.
AB - X-ray free electron lasers (XFEL) provide intense and almost coherent X-ray
pulses. They are used for various experiments investigating physical and chemical
properties in materials and biological science because of their complete
coherence, high intensity, and very short pulse width. In XFEL experiments,
specimens are irradiated by XFEL pulses focused by mirror optics. The focused
pulse is too intense to measure its coherence by placing an X-ray detector on the
focal spot. Previously, a method was proposed for evaluating the coherence of
focused pulses from the visibility of the diffraction intensity of colloidal
particles by the speckle visibility spectroscopy (SVS). However, the visibility
cannot be determined exactly because the diffraction intensity is integrated into
each finite size detector pixel. Here, we propose a method to evaluate the
coherence of each XFEL pulse by using SVS in combination with a theory for exact
sampling of the diffraction pattern and a technique of multiplying the
diffraction data by a Gaussian masks, which reduces the influence of data missing
in small-angle regions due to the presence of a direct beamstop. We also
introduce a method for characterizing the shot-by-shot size of each XFEL pulse by
analysing the X-ray irradiated area.
PMID- 29339757
TI - Melatonin increases chilling tolerance in postharvest peach fruit by alleviating
oxidative damage.
AB - Melatonin has been reported to alleviate chilling symptoms in postharvest peach
fruit during cold storage, however, the mechanism involved is largely unknown. To
better understand its role in chilling tolerance, here we investigated the
effects of melatonin on oxidative damage in peach fruit subjected to chilling
after harvest. Chilling injury of peaches was dramatically reduced by melatonin
treatment. Melatonin induced hydrogen peroxide (H2O2) content at the early stage
of storage but inhibited its accumulation thereafter. Meanwhile, melatonin also
up-regulated the expression of genes involved in antioxidant responses in
peaches. In addition, compared to the control fruit, peaches treated with
melatonin displayed higher transcript abundance of ascorbic acid (AsA)
biosynthetic genes and consequently increased the AsA content. Our results
suggested that in response to melatonin during chilling, the high H2O2 level in
the treated peaches at the initial time of storage, may work as a signaling
molecule to induce protective mechanisms via up-regulating the expression of
antioxidative genes and increasing AsA content. On the other hand, after the
transient increase in the treated peaches, H2O2 was efficiently removed because
of the activated antioxidant systems, which was associated with the higher
chilling tolerance induced by melatonin.
PMID- 29339758
TI - MiRNA-seq-based profiles of miRNAs in mulberry phloem sap provide insight into
the pathogenic mechanisms of mulberry yellow dwarf disease.
AB - A wide range of miRNAs have been identified as phloem-mobile molecules that play
important roles in coordinating plant development and physiology. Phytoplasmas
are associated with hundreds of plant diseases, and the pathogenesis involved in
the interactions between phytoplasmas and plants is still poorly understood. To
analyse the molecular mechanisms of phytoplasma pathogenicity, the miRNAs
profiles in mulberry phloem saps were examined in response to phytoplasma
infection. A total of 86 conserved miRNAs and 19 novel miRNAs were identified,
and 30 conserved miRNAs and 13 novel miRNAs were differentially expressed upon
infection with phytoplasmas. The target genes of the differentially expressed
miRNAs are involved in diverse signalling pathways showing the complex
interactions between mulberry and phytoplasma. Interestingly, we found that mul
miR482a-5p was up-regulated in the infected phloem saps, and grafting experiments
showed that it can be transported from scions to rootstock. Based on the results,
the complexity and roles of the miRNAs in phloem sap and the potential molecular
mechanisms of their changes were discussed. It is likely that the phytoplasma
responsive miRNAs in the phloem sap modulate multiple pathways and work
cooperatively in response to phytoplasma infection, and their expression changes
may be responsible for some symptoms in the infected plants.
PMID- 29339759
TI - Optimized chaotic Brillouin dynamic grating with filtered optical feedback.
AB - Chaotic Brillouin dynamic gratings (BDGs) have special advantages such as the
creation of single, permanent and localized BDG. However, the periodic signals
induced by conventional optical feedback (COF) in chaotic semiconductor lasers
can lead to the generation of spurious BDGs, which will limit the application of
chaotic BDGs. In this paper, filtered optical feedback (FOF) is proposed to
eliminate spurious BDGs. By controlling the spectral width of the optical filter
and its detuning from the laser frequency, semiconductor lasers with FOF operate
in the suppression region of the time-delay signature, and chaotic outputs
serving as pump waves are then utilized to generate the chaotic BDG in a
polarization maintaining fiber. Through comparative analysis of the COF and FOF
schemes, it has been demonstrated that spurious BDGs are effectively eliminated
and that the reflection characterization of the chaotic BDG is improved. The
influence of FOF on the reflection and gain spectra of the chaotic BDG is
analyzed as well.
PMID- 29339760
TI - Biochemical and genetic characterization of a novel metallo-beta-lactamase from
marine bacterium Erythrobacter litoralis HTCC 2594.
AB - Metallo-beta-lactamases (MBLs) are a group of enzymes that can inactivate most
commonly used beta-lactam-based antibiotics. Among MBLs, New Delhi metallo-beta
lactamase-1 (NDM-1) constitutes an urgent threat to public health as evidenced by
its success in rapidly disseminating worldwide since its first discovery. Here we
report the biochemical and genetic characteristics of a novel MBL, ElBla2, from
the marine bacterium Erythrobacter litoralis HTCC 2594. This enzyme has a higher
amino acid sequence similarity to NDM-1 (56%) than any previously reported MBL.
Enzymatic assays and secondary structure alignment also confirmed the high
similarity between these two enzymes. Whole genome comparison of four
Erythrobacter species showed that genes located upstream and downstream of elbla2
were highly conserved, which may indicate that elbla2 was lost during evolution.
Furthermore, we predicted two prophages, 13 genomic islands and 25 open reading
frames related to insertion sequences in the genome of E. litoralis HTCC 2594.
However, unlike NDM-1, the chromosome encoded ElBla2 did not locate in or near
these mobile genetic elements, indicating that it cannot transfer between
strains. Finally, following our phylogenetic analysis, we suggest a
reclassification of E. litoralis HTCC 2594 as a novel species: Erythrobacter sp.
HTCC 2594.
PMID- 29339761
TI - New virulence factor CSK29544_02616 as LpxA binding partner in Cronobacter
sakazakii.
AB - Cronobacter sakazakii is an opportunistic pathogen that can cause meningitis and
necrotizing enterocolitis in premature infants, but its virulence determinants
remain largely unknown. In this study, a transposon-mediated random-mutant
library of C. sakazakii was used to identify new virulence factors. Compared to
wild-type bacteria, a mutant lacking CSK29544_02616 (referred to as labp) was
defective in invasion into intestinal epithelial cells (by at least 1000-fold)
and showed less phagocytosis by macrophages (by at least 50-fold). The lack of
labp in C. sakazakii changed the profile of outer membrane proteins, decreased
the production of lipopolysaccharides, and increased the production of membrane
phospholipids. Bacterial physiological characteristics including surface
hydrophobicity and motility were also altered in the absence of labp, presumably
because of changes in the bacterial-envelope structure. To systematically
determine the role of labp, ligand fishing was conducted using Labp as a bait,
which revealed LpxA as a binding partner of Labp. LpxA is UDP-N-acetylglucosamine
(GlcNAc) acyltransferase, the first enzyme in the pathway of lipid A
biosynthesis. Labp increased the enzymatic activity of LpxA without influencing
lpxA expression. Considering multifaceted roles of lipopolysaccharides in
virulence regulation, Labp is a novel virulence factor that promotes the
production of lipid A by LpxA in Cronobacter.
PMID- 29339764
TI - Four-dimensional entanglement distribution over 100 km.
AB - High-dimensional quantum entanglement can enrich the functionality of quantum
information processing. For example, it can enhance the channel capacity for
linear optic superdense coding and decrease the error rate threshold of quantum
key distribution. Long-distance distribution of a high-dimensional entanglement
is essential for such advanced quantum communications over a communications
network. Here, we show a long-distance distribution of a four-dimensional
entanglement. We employ time-bin entanglement, which is suitable for a fibre
transmission, and implement scalable measurements for the high-dimensional
entanglement using cascaded Mach-Zehnder interferometers. We observe that a pair
of time-bin entangled photons has more than 1 bit of secure information capacity
over 100 km. Our work constitutes an important step towards secure and dense
quantum communications in a large Hilbert space.
PMID- 29339762
TI - Supra-pharmacological concentration of capsaicin stimulates brown adipogenesis
through induction of endoplasmic reticulum stress.
AB - We previously showed that brown (pre)adipocytes express Trpv1, a capsaicin
receptor, and that capsaicin stimulates differentiation of brown preadipocytes in
the late stages of brown adipogenesis. The present study revealed that treatment
with 100 MUM capsaicin stimulates brown adipogenesis by inducing endoplasmic
reticulum (ER) stress. Treatment with capsaicin (100 MUM) during brown
adipogenesis enhanced lipid accumulation and the expression of Ucp1, a gene
selectively expressed in brown adipocytes. Capsaicin treatment also caused an
increase in the cytosolic calcium concentration even when extracellular calcium
was removed. I-RTX, a Trpv1 inhibitor, did not modulate the increase in cytosolic
calcium concentration, lipid accumulation or Ucp1 expression. Previous studies
revealed that the release of calcium from the ER induces ER stress, leading to
the conversion of X-box binding protein 1 (Xbp1) pre-mRNA to spliced Xbp1 (sXbp1)
as well as the up-regulation of Chop expression. Capsaicin treatment increased
the expression of sXbp1 and Chop in brown preadipocytes and did not enhance lipid
accumulation or Ucp1 expression in Xbp1 knockdown cells. The present results
describe a novel mechanism of brown adipogenesis regulation via ER stress that is
induced by a supra-pharmacological concentration of capsaicin.
PMID- 29339763
TI - Glucocorticoid receptor GRbeta regulates glucocorticoid-induced ocular
hypertension in mice.
AB - Prolonged glucocorticoid (GC) therapy can cause GC-induced ocular hypertension
(OHT), which if left untreated progresses to iatrogenic glaucoma and permanent
vision loss. The alternatively spliced isoform of glucocorticoid receptor GRbeta
acts as dominant negative regulator of GR activity, and it has been shown that
overexpressing GRbeta in trabecular meshwork (TM) cells inhibits GC-induced
glaucomatous damage in TM cells. The purpose of this study was to use viral
vectors to selectively overexpress the GRbeta isoform in the TM of mouse eyes
treated with GCs, to precisely dissect the role of GRbeta in regulating steroid
responsiveness. We show that overexpression of GRbeta inhibits GC effects on MTM
cells in vitro and GC-induced OHT in mouse eyes in vivo. Ad5 mediated GRbeta
overexpression reduced the GC induction of fibronectin, collagen 1, and myocilin
in TM of mouse eyes both in vitro and in vivo. GRbeta also reversed DEX-Ac
induced IOP elevation, which correlated with increased conventional aqueous humor
outflow facility. Thus, GRbeta overexpression reduces effects caused by GCs and
makes cells more resistant to GC treatment. In conclusion, our current work
provides the first evidence of the in vivo physiological role of GRbeta in
regulating GC-OHT and GC-mediated gene expression in the TM.
PMID- 29339765
TI - Mutations in bassoon in individuals with familial and sporadic progressive
supranuclear palsy-like syndrome.
AB - Clinical diagnosis of progressive supranuclear palsy (PSP) is sometimes difficult
because various phenotypes have been identified. Here, we report a mutation in
the bassoon (BSN) gene in a family with PSP-like syndrome. Their clinical
features resembled not only those of PSP patients but also those of individuals
with multiple system atrophy and Alzheimer's disease. The neuropathological
findings showed a novel three + four repeat tauopathy with pallido-luysio-nigral
degeneration and hippocampal sclerosis. Whole-exome analysis of this family
identified a novel missense mutation in BSN. Within the pedigree, the detected
BSN mutation was found only in affected individuals. Further genetic analyses
were conducted in probands from four other pedigrees with PSP-like syndrome and
in 41 sporadic cases. Three missense mutations in BSN that are very rarely listed
in databases of healthy subjects were found in four sporadic cases. Western blot
analysis of tau following the overexpression of wild-type or mutated BSN revealed
the possibility that wild-type BSN reduced tau accumulation, while mutated BSN
lost this function. An association between BSN and neurological diseases has not
been previously reported. Our results revealed that the neurodegenerative
disorder associated with the original proband's pedigree is a novel tauopathy,
differing from known dementia and parkinsonism syndromes, including PSP.
PMID- 29339766
TI - The crystal structure of D-xylonate dehydratase reveals functional features of
enzymes from the Ilv/ED dehydratase family.
AB - The Ilv/ED dehydratase protein family includes dihydroxy acid-, gluconate-, 6
phosphogluconate- and pentonate dehydratases. The members of this family are
involved in various biosynthetic and carbohydrate metabolic pathways. Here, we
describe the first crystal structure of D-xylonate dehydratase from Caulobacter
crescentus (CcXyDHT) at 2.7 A resolution and compare it with other available
enzyme structures from the IlvD/EDD protein family. The quaternary structure of
CcXyDHT is a tetramer, and each monomer is composed of two domains in which the N
terminal domain forms a binding site for a [2Fe-2S] cluster and a Mg2+ ion. The
active site is located at the monomer-monomer interface and contains residues
from both the N-terminal recognition helix and the C-terminus of the dimeric
counterpart. The active site also contains a conserved Ser490, which probably
acts as a base in catalysis. Importantly, the cysteines that participate in the
binding and formation of the [2Fe-2S] cluster are not all conserved within the
Ilv/ED dehydratase family, which suggests that some members of the IlvD/EDD
family may bind different types of [Fe-S] clusters.
PMID- 29339767
TI - Regulatory T cells trigger effector T cell DNA damage and senescence caused by
metabolic competition.
AB - Defining the suppressive mechanisms used by regulatory T (Treg) cells is critical
for the development of effective strategies for treating tumors and chronic
infections. The molecular processes that occur in responder T cells that are
suppressed by Treg cells are unclear. Here we show that human Treg cells initiate
DNA damage in effector T cells caused by metabolic competition during cross-talk,
resulting in senescence and functional changes that are molecularly distinct from
anergy and exhaustion. ERK1/2 and p38 signaling cooperate with STAT1 and STAT3 to
control Treg-induced effector T-cell senescence. Human Treg-induced T-cell
senescence can be prevented via inhibition of the DNA damage response and/or STAT
signaling in T-cell adoptive transfer mouse models. These studies identify
molecular mechanisms of human Treg cell suppression and indicate that targeting
Treg-induced T-cell senescence is a checkpoint for immunotherapy against cancer
and other diseases associated with Treg cells.
PMID- 29339768
TI - The characterization of the circadian clock in the olive fly Bactrocera oleae
(Diptera: Tephritidae) reveals a Drosophila-like organization.
AB - The olive fruit fly, Bactrocera oleae, is the single most important pest for the
majority of olive plantations. Oxitec's self-limiting olive fly technology
(OX3097D-Bol) offers an alternative management approach to this insect pest.
Because of previously reported asynchrony in the mating time of wild and
laboratory strains, we have characterized the olive fly circadian clock applying
molecular, evolutionary, anatomical and behavioural approaches. Here we
demonstrate that the olive fly clock relies on a Drosophila melanogaster-like
organization and that OX3097D-Bol carries a functional clock similar to wild-type
strains, confirming its suitability for operational use.
PMID- 29339769
TI - Universal Transient Dynamics of Electrowetting Droplets.
AB - Droplet spreading on substrates by electrowetting exhibits either of the two
transient behaviours: one characterised by contact line oscillation, and the
other one by slow spreading dynamics. The transition between these behaviours
remains elusive due to the current limited understanding of the spreading
dynamics on the hydrodynamical and electrical properties of electrowetting
systems. To understand this transition we propose a model capturing the
transition's occurrence based on both the hydrodynamical and electrical
parameters. We derive the critical viscosity at which the transition occurs and
reveal its subtle and often hidden dependence on the electrowetting dynamics. We
find and experimentally verify that the condition for minimization of droplets'
actuation time is only achieved at the transition. Particularly, the transition
time as a function of damping ratio exhibits the general feature of Kramers'
reaction-rate theory.
PMID- 29339770
TI - Reversing Cocaine-Induced Adaptations and Reducing Relapse: An Opportunity for
Repurposing Riluzole.
PMID- 29339771
TI - Etiology of language network changes during recovery of aphasia after stroke.
AB - Knowledge of spatiotemporal patterns of language network changes may help in
predicting outcome in aphasic stroke patients. Here we assessed language function
and performed functional MRI four times during one year to measure language
network activation and cerebrovascular reactivity (with breath-holding) in twelve
left-hemispheric stroke patients, of whom two dropped out before the final
measurement, and eight age-matched controls. Language outcome was related to
increase of activation in left and right posterior inferior temporal gyrus over
the first year, while activation increase in right inferior frontal gyrus was
inversely correlated to language recovery. Outcome prediction improved by
addition of early language-induced activation of the left posterior inferior
temporal gyrus to a regression model with baseline language performance as first
predictor. Variations in language-induced activation in right inferior frontal
gyrus were primarily related to differences in vascular reactivity. Furthermore,
several language-activation changes could not be linked to alterations in
language proficiency nor vascular reactivity, and were assumed to be caused by
unspecified intersession variability. In conclusion, early functional
neuroimaging improves outcome prediction of aphasia after stroke. Controlling for
cerebrovascular reactivity and unspecified intersession variability may result in
more accurate assessment of the relationship between activation pattern shifts
and function after stroke.
PMID- 29339772
TI - Foxo1 Promotes Th9 Cell Differentiation and Airway Allergy.
AB - T helper 9 (Th9) cells are effector CD4+ T cells that are characterized by the
production of interleukin-9 (IL-9) and have been associated with allergic
responses. Here, we found that the expression of the transcription factor
forkhead box O1 (Foxo1) was induced in Th9 and Foxo1 plays a crucial role in the
differentiation of Th9 cells. Pharmacological inhibition of Foxo1 or genetic
disruption of Foxo1 in CD4+ T cells caused a reduction in IL-9 expression while
upregulating IL-17A and IFNgamma production. Furthermore, chromatin
immunoprecipitation (ChIP) followed by luciferase assays revealed direct binding
of Foxo1 to both the Il9 and Irf4 promoters and induces their transactivation.
Lastly, adoptive transfer of Th9 cells into lungs induced asthma-like symptoms
that were ameliorated by Foxo1 inhibitor, AS1842856. Together, our findings
demonstrate a novel regulator of Th9 cells with a direct implication in allergic
inflammation.
PMID- 29339774
TI - Erratum: Sensory augmentation: integration of an auditory compass signal into
human perception of space.
AB - This corrects the article DOI: 10.1038/srep42197.
PMID- 29339773
TI - Postural adaptations to unilateral knee joint hypomobility induced by orthosis
wear during gait initiation.
AB - Balance control and whole-body progression during gait initiation (GI) involve
knee-joint mobility. Single knee-joint hypomobility often occurs with aging,
orthopedics or neurological conditions. The goal of the present study was to
investigate the capacity of the CNS to adapt GI organization to single knee-joint
hypomobility induced by the wear of an orthosis. Twenty-seven healthy adults
performed a GI series on a force-plate in the following conditions: without
orthosis ("control"), with knee orthosis over the swing leg ("orth-swing") and
with the orthosis over the contralateral stance leg ("orth-stance"). In orth
swing, amplitude of mediolateral anticipatory postural adjustments (APAs) and
step width were larger, execution phase duration longer, and anteroposterior APAs
smaller than in control. In orth-stance, mediolateral APAs duration was longer,
step width larger, and amplitude of anteroposterior APAs smaller than in control.
Consequently, step length and progression velocity (which relate to the "motor
performance") were reduced whereas stability was enhanced compared to control.
Vertical force impact at foot-contact did not change across conditions, despite a
smaller step length in orthosis conditions compared to control. These results
show that the application of a local mechanical constraint induced profound
changes in the global GI organization, altering motor performance but ensuring
greater stability.
PMID- 29339775
TI - Anti-apoptotic A1 is not essential for lymphoma development in Eu-Myc mice but
helps sustain transplanted Eu-Myc tumour cells.
AB - The transcription factor c-MYC regulates a multiplicity of genes involved in
cellular growth, proliferation, metabolism and DNA damage response and its
overexpression is a hallmark of many tumours. Since MYC promotes apoptosis under
conditions of stress, such as limited availability of nutrients or cytokines, MYC
driven cells are very much dependent on signals that inhibit cell death. Stress
signals trigger apoptosis via the pathway regulated by opposing fractions of the
BCL-2 protein family and previous genetic studies have shown that the development
of B lymphoid tumours in Eu-Myc mice is critically dependent on expression of pro
survival BCL-2 relatives MCL-1, BCL-W and, to a lesser extent, BCL-XL, but not
BCL-2 itself, and that sustained growth of these lymphomas is dependent on MCL-1.
Using recently developed mice that lack expression of all three functional pro
survival A1 genes, we show here that the kinetics of lymphoma development in Eu
Myc mice and the competitive repopulation capacity of Eu-Myc haemopoietic stem
and progenitor cells is unaffected by the absence of A1. However, conditional
loss of a single remaining functional A1 gene from transplanted A1-a-/-A1-b fl/fl
A1-c-/- Eu-Myc lymphomas slowed their expansion, significantly extending the life
of the transplant recipients. Thus, A1 contributes to the survival of malignant
Eu-Myc-driven B lymphoid cells. These results strengthen the case for BFL-1, the
human homologue of A1, being a valid target for drug development for MYC-driven
tumours.
PMID- 29339776
TI - The experience of spasticity after spinal cord injury: perceived characteristics
and impact on daily life.
AB - STUDY DESIGN: Cross-sectional survey. OBJECTIVES: Determine the impact of motor
control characteristics attributed to spasticity, such as spasms, stiffness, and
clonus on the daily life of people with spinal cord injury (SCI). SETTING:
Nationwide, United States. METHODS: Internet-administered questionnaire, the
Patient Reported Impact of Spasticity Measure (PRISM) and items describing
characteristics of spasticity including stiffness, spasms, clonus, and pain.
RESULTS: Of the 145 respondents, 113 (78%) reported a PRISM score of at least
5/164, indicating spasticity had some impact on their daily lives. Stiffness
impact was highly correlated (rho = 0.84; p < 0.01) with the PRISM negative
impact on Daily Activities subscale and moderately correlated with the other
PRISM subscales (rho = 0.55-0.63; p < 0.01). Spasm presence had a negligible or
low correlation with PRISM negative impact subscales (rho = 0.29-0.47; p < 0.01).
Trunk muscle stiffness and spasms had a low correlation with PRISM Need for
Assistance and Daily activities (rho = 0.42 and rho = 0.41, p < 0.01,
respectively). Anti-spasticity medications were ineffective for 58% of
respondents. Pain in the legs was reported by 57% of respondents. CONCLUSIONS:
The experience of spasticity is highly individualized, and is often distributed
differently across arms, trunk, and legs. Despite the fact that traditional
definitions of spasticity focus on reflex responsiveness, the stiffness
associated with spasticity appears to be more problematic than spasms or clonus.
The self-described characteristics of spasticity and its physiological
presentation are complex and related to pain. This varied presentation lends
support to the concept that management of spasticity may be best achieved by
multimodality strategies.
PMID- 29339777
TI - Regulation of the Response of Caenorhabditis elegans to Simulated Microgravity by
p38 Mitogen-Activated Protein Kinase Signaling.
AB - The in vivo function of p38 mitogen-activated protein kinase (MAPK) signaling in
regulating the response to simulated microgravity is still largely unclear. Using
Caenorhabditis elegans as an assay system, we investigated the in vivo function
of p38 MAPK signaling in regulating the response of animals to simulated
microgravity and the underlying molecular mechanism. Simulated microgravity
treatment significantly increased the transcriptional expressions of genes (pmk
1, sek-1, and nsy-1) encoding core p38 MAPK signaling pathway and the expression
of phosphorylated PMK-1/p38 MAPK. The pmk-1, sek-1, or nsy-1 mutant was
susceptible to adverse effects of simulated microgravity. The intestine-specific
activity of PMK-1 was required for its function in regulating the response to
simulated microgravity, and the entire p38 MAPK signaling pathway could act in
the intestine to regulate the response to simulated microgravity. In the
intestine, SKN-1 and ATF-7, two transcriptional factors, were identified as
downstream targets for PMK-1 in regulating the response to simulated
microgravity. Therefore, the activation of p38 MAPK signaling may mediate a
protection mechanism for nematodes against the adverse effects of simulated
microgravity. Additionally, our results highlight the potential crucial role of
intestinal cells in response to simulated microgravity in nematodes.
PMID- 29339778
TI - A novel human muscle cell model of Duchenne muscular dystrophy created by
CRISPR/Cas9 and evaluation of antisense-mediated exon skipping.
AB - Oligonucleotide-mediated splicing modulation is a promising therapeutic approach
for Duchenne muscular dystrophy (DMD). Recently, eteplirsen, a phosphorodiamidate
morpholino oligomer-based splice-switching oligonucleotide (SSO) targeting DMD
exon 51, was approved by the U.S. Food and Drug Administration as the first
antisense-based drug for DMD patients. For further exploring SSOs targeting other
exons in the DMD gene, the efficacy of exon skipping and protein rescue with each
SSO sequence needs evaluations in vitro. However, only a few immortalized muscle
cell lines derived from DMD patients have been reported and are available to test
the efficacy of exon skipping in vitro. To solve this problem, we generated a
novel immortalized DMD muscle cell line from the human rhabdomyosarcoma (RD) cell
line. We removed DMD exons 51-57 (~0.3 Mb) in the RD cell line using the
CRISPR/Cas9 system. Additionally, in this DMD model cell line, we evaluated the
exon 50 skipping activity of previously reported SSOs at both the mRNA and
protein levels. CRISPR/Cas9-mediated gene editing of the DMD gene in the RD cell
line will allow for assessment of SSOs targeting most of the rare mutations in
the DMD gene.
PMID- 29339779
TI - Novel recessive mutations in MSTO1 cause cerebellar atrophy with pigmentary
retinopathy.
AB - Misato 1, mitochondrial distribution and morphology regulator (encoded by the
MSTO1 gene), is involved in mitochondrial distribution and morphology. Recently,
MSTO1 mutations have been shown to cause clinical manifestations suggestive of
mitochondrial dysfunction, such as muscle weakness, short stature, motor
developmental delay, and cerebellar atrophy. Both autosomal dominant and
recessive modes of inheritance have been suggested. We performed whole-exome
sequencing in two unrelated patients showing cerebellar atrophy, intellectual
disability, and pigmentary retinopathy. Three novel mutations were identified:
c.836 G > A (p.Arg279His), c.1099-1 G > A (p.Val367Trpfs*2), and c.79 C > T
(p.Gln27*). Both patients had compound heterozygous mutations with a combination
of protein-truncation mutation and missense mutation, the latter shared by them
both. This survey of two patients with recessive and novel MSTO1 mutations
provides additional clinical and genetic information on the pathogenicity of
MSTO1 in humans.
PMID- 29339780
TI - Extractable pool of biochar controls on crop productivity rather than greenhouse
gas emission from a rice paddy under rice-wheat rotation.
AB - The role of extractable pool of biochar in crop productivity and soil greenhouse
gas (GHGs) emission is not yet clear. In this study, two biochars with and
without extraction was added to a paddy before rice transplantation at 20 t.ha-1.
Crop yield, plant traits and greenhouse gas emission monitored throughout a rice
wheat rotation. Between the biochar treatments, changes in bulk density and
microbial biomass carbon were insignificant. However, the increase in organic
carbon was similar between maize and wheat biochars while higher under bulk wheat
biochar than extracted one. The increase in available P and K was higher under
wheat than maize biochar regardless of extraction. Moreover, the increase in
plant traits and grain yield, in rice season only, was higher under bulk than
extracted biochars. Yet, there was no difference in changes in GHGs emission
between bulk and extracted biochars regardless of feedstock. Nevertheless,
increased methane emission for rice season was lower under extracted biochars
than bulk ones. Overall, crop productivity rather than GHGs emission was affected
by treatment of extraction of biochars. Thus, use of unextracted biochar is
recommended for improving soil crop productivity in the paddy soils.
PMID- 29339781
TI - Draxin regulates hippocampal neurogenesis in the postnatal dentate gyrus by
inhibiting DCC-induced apoptosis.
AB - Hippocampal neurogenesis in the dentate gyrus (DG) is controlled by diffusible
molecules that modulate neurogenic processes, including cell proliferation,
differentiation and survival. To elucidate the mechanisms underlying hippocampal
neurogenesis, we investigated the function of draxin, originally identified as a
neural chemorepellent, in the regulation of neuronal survival in the DG. Draxin
was expressed in Tbr2 (+) late progenitors and NeuroD1 (+) neuroblasts in the
dentate granule cell lineage, whereas expression of its receptor DCC (deleted in
colorectal cancer) was mainly detectable in neuroblasts. Our phenotypic analysis
revealed that draxin deficiency led to enhanced apoptosis of DCC-expressing
neuroblasts in the neurogenic areas. Furthermore, in vitro assays using a
hippocampal neural stem/progenitor cell (HNSPC) line indicated that draxin
inhibited apoptosis in differentiating HNSPCs, which express DCC. Taken together,
we postulate that draxin plays a pivotal role in postnatal DG neurogenesis as a
dependence receptor ligand for DCC to maintain and promote survival of
neuroblasts.
PMID- 29339782
TI - Loss of disease tolerance during Citrobacter rodentium infection is associated
with impaired epithelial differentiation and hyperactivation of T cell responses.
AB - Citrobacter rodentium is an intestinal mouse pathogen widely used as a model to
study the mucosal response to infection. Inbred mouse strains suffer one of two
fates following infection: self-limiting colitis or fatal diarrheal disease. We
previously reported that Rspo2 is a major genetic determinant of the outcome of
C. rodentium infection; Rspo2 induction during infection of susceptible mice
leads to loss of intestinal function and mortality. Rspo2 induction does not
impact bacterial colonization, but rather, impedes the ability of the host to
tolerate C. rodentium infection. Here, we performed deep RNA sequencing and
systematically analyzed the global gene expression profiles of C. rodentium
infected colon tissues from susceptible and resistant congenic mice strains to
determine the common responses to infection and the Rspo2-mediated dysfunction
pathway signatures associated with loss of disease tolerance. Our results
highlight changes in metabolism, tissue remodeling, and host defence as common
responses to infection. Conversely, increased Wnt and stem cell signatures, loss
of epithelial differentiation, and exaggerated CD4+ T cell activation through
increased antigen processing and presentation were specifically associated with
the response to infection in susceptible mice. These data provide insights into
the molecular mechanisms underlying intestinal dysfunction and disease tolerance
during C. rodentium infection.
PMID- 29339783
TI - Global and regional importance of the direct dust-climate feedback.
AB - Feedbacks between the global dust cycle and the climate system might have
amplified past climate changes. Yet, it remains unclear what role the dust
climate feedback will play in future anthropogenic climate change. Here, we
estimate the direct dust-climate feedback, arising from changes in the dust
direct radiative effect (DRE), using a simple theoretical framework that combines
constraints on the dust DRE with a series of climate model results. We find that
the direct dust-climate feedback is likely in the range of -0.04 to +0.02 Wm -2 K
1, such that it could account for a substantial fraction of the total aerosol
feedbacks in the climate system. On a regional scale, the direct dust-climate
feedback is enhanced by approximately an order of magnitude close to major source
regions. This suggests that it could play an important role in shaping the future
climates of Northern Africa, the Sahel, the Mediterranean region, the Middle
East, and Central Asia.
PMID- 29339784
TI - Anisotropic sensor and memory device with a ferromagnetic tunnel barrier as the
only magnetic element.
AB - Multiple spin functionalities are probed on Pt/La2Co0.8Mn1.2O6/Nb:SrTiO3, a
device composed by a ferromagnetic insulating barrier sandwiched between non
magnetic electrodes. Uniquely, La2Co0.8Mn1.2O6 thin films present strong
perpendicular magnetic anisotropy of magnetocrystalline origin, property of major
interest for spintronics. The junction has an estimated spin-filtering efficiency
of 99.7% and tunneling anisotropic magnetoresistance (TAMR) values up to 30% at
low temperatures. This remarkable angular dependence of the magnetoresistance is
associated with the magnetic anisotropy whose origin lies in the large spin-orbit
interaction of Co2+ which is additionally tuned by the strain of the crystal
lattice. Furthermore, we found that the junction can operate as an electrically
readable magnetic memory device. The findings of this work demonstrate that a
single ferromagnetic insulating barrier with strong magnetocrystalline anisotropy
is sufficient for realizing sensor and memory functionalities in a tunneling
device based on TAMR.
PMID- 29339785
TI - The lncRNA GATA6-AS epigenetically regulates endothelial gene expression via
interaction with LOXL2.
AB - Impaired or excessive growth of endothelial cells contributes to several
diseases. However, the functional involvement of regulatory long non-coding RNAs
in these processes is not well defined. Here, we show that the long non-coding
antisense transcript of GATA6 (GATA6-AS) interacts with the epigenetic regulator
LOXL2 to regulate endothelial gene expression via changes in histone methylation.
Using RNA deep sequencing, we find that GATA6-AS is upregulated in endothelial
cells during hypoxia. Silencing of GATA6-AS diminishes TGF-beta2-induced
endothelial-mesenchymal transition in vitro and promotes formation of blood
vessels in mice. We identify LOXL2, known to remove activating H3K4me3 chromatin
marks, as a GATA6-AS-associated protein, and reveal a set of angiogenesis-related
genes that are inversely regulated by LOXL2 and GATA6-AS silencing. As GATA6-AS
silencing reduces H3K4me3 methylation of two of these genes, periostin and
cyclooxygenase-2, we conclude that GATA6-AS acts as negative regulator of nuclear
LOXL2 function.
PMID- 29339786
TI - Integrated miRNA-mRNA spatial signature for oral squamous cell carcinoma: a
prospective profiling study of Narrow Band Imaging guided resection.
AB - Oral squamous cell carcinoma (OSCC) is a common malignancy for which there is
poor prognosis and limited therapeutic options. The objective was to identify
mRNA targets of dysregulated miRNAs in OSCC using integrated analysis and
understand molecular abnormality in surgical margins. We used biopsies along the
spatial axis from normal tissue defined by narrow band imaging (NBI) through
conventional white light (WL) margins to tumour from 18 patients undergoing
surgical resection for OSCC. Overall 119 miRNA and 4794 mRNA were differentially
expressed along the adjacent normal tissue to tumour axis. Analysis of miRNA
profiles demonstrated the NBI margins were molecularly distinct from both the
tumour and WL margin. Integrated analysis identified 193 miRNA-mRNA interactions
correlated to the spatial axis of NBI-WL-T. We used cross-validation analysis to
derive a spatial interactome signature of OSCC comprising 100 putative miRNA-mRNA
interactions between 40 miRNA and 96 mRNA. Bioinformatic analysis suggests that
miRNA dysregulation in OSCC may contribute to activation of the oncostatin M,
BDNF and TGF-beta pathways. Our data demonstrates that surgical margins defined
by NBI leave less potentially malignant residual tissue. The miRNA-mRNA
interactome provides insight into dysregulated miRNA signalling in OSCC and
supports molecular definition of tumour margins.
PMID- 29339787
TI - Cilia-related protein SPEF2 regulates osteoblast differentiation.
AB - Sperm flagellar protein 2 (SPEF2) is essential for motile cilia, and lack of
SPEF2 function causes male infertility and primary ciliary dyskinesia. Cilia are
pointing out from the cell surface and are involved in signal transduction from
extracellular matrix, fluid flow and motility. It has been shown that cilia and
cilia-related genes play essential role in commitment and differentiation of
chondrocytes and osteoblasts during bone formation. Here we show that SPEF2 is
expressed in bone and cartilage. The analysis of a Spef2 knockout (KO) mouse
model revealed hydrocephalus, growth retardation and death prior to five weeks of
age. To further elucidate the causes of growth retardation we analyzed the bone
structure and possible effects of SPEF2 depletion on bone formation. In Spef2 KO
mice, long bones (tibia and femur) were shorter compared to wild type, and X-ray
analysis revealed reduced bone mineral content. Furthermore, we showed that the
in vitro differentiation of osteoblasts isolated from Spef2 KO animals was
compromised. In conclusion, this study reveals a novel function for SPEF2 in bone
formation through regulation of osteoblast differentiation and bone growth.
PMID- 29339788
TI - Band gap maps beyond the delocalization limit: correlation between optical band
gaps and plasmon energies at the nanoscale.
AB - Recent progresses in nanoscale semiconductor technology have heightened the need
for measurements of band gaps with high spatial resolution. Band gap mapping can
be performed through a combination of probe-corrected scanning transmission
electron microscopy (STEM) and monochromated electron energy-loss spectroscopy
(EELS), but are rare owing to the complexity of the experiments and the data
analysis. Furthermore, although this method is far superior in terms of spatial
resolution to any other techniques, it is still fundamentally resolution-limited
due to inelastic delocalization of the EELS signal. In this work we have
established a quantitative correlation between optical band gaps and plasmon
energies using the Zn1-xCd x O/ZnO system as an example, thereby side-stepping
the fundamental resolution limits of band gap measurements, and providing a
simple and convenient approach to achieve band gap maps with unprecedented
spatial resolution.
PMID- 29339790
TI - Decoding the dynamic representation of musical pitch from human brain activity.
AB - In music, the perception of pitch is governed largely by its tonal function given
the preceding harmonic structure of the music. While behavioral research has
advanced our understanding of the perceptual representation of musical pitch,
relatively little is known about its representational structure in the brain.
Using Magnetoencephalography (MEG), we recorded evoked neural responses to
different tones presented within a tonal context. Multivariate Pattern Analysis
(MVPA) was applied to "decode" the stimulus that listeners heard based on the
underlying neural activity. We then characterized the structure of the brain's
representation using decoding accuracy as a proxy for representational distance,
and compared this structure to several well established perceptual and acoustic
models. The observed neural representation was best accounted for by a model
based on the Standard Tonal Hierarchy, whereby differences in the neural encoding
of musical pitches correspond to their differences in perceived stability. By
confirming that perceptual differences honor those in the underlying neuronal
population coding, our results provide a crucial link in understanding the
cognitive foundations of musical pitch across psychological and neural domains.
PMID- 29339789
TI - Exosome-mediated breast cancer chemoresistance via miR-155 transfer.
AB - Breast cancer remains the most prevalent cause of cancer mortality in woman
worldwide due to the metastatic process and therapy resistance. Resistance
against cancer therapy is partially attributed to cancer stem cells (CSCs). These
cells arise from epithelial cells undergoing epithelial-to-mesenchymal transition
(EMT) and might be responsible for tumor recurrence. In this study, we reported
the relevance of miR-155 upregulation in chemoresistant cells associated with
EMT. Notably, we found miR-155 induction in exosomes isolated from CSCs and
resistant cells, followed by resistant cells' exosome transfer to the recipient
sensitive cells. Functionally, miR-155 mimic assay showed an enrichment in miR
155 from exosome concomitant with miR-155 exosome transfer to breast cancer
cells. In parallel to these effects, we also observed EMT change in miR-155
transfected cells. The chemoresistance phenotype transfer to sensitive cells and
the migration capability was analyzed by MTT and scratch assays and our results
suggest that exosomes may intermediate resistance and migration capacity to
sensitive cells partly through exosome transfer of miR-155. Taken together, our
findings establish the significance of exosome-mediate miR-155 chemoresistance in
breast cancer cells, with implications for targeting miR-155 signaling as a
possible therapeutic strategy.
PMID- 29339792
TI - Assemble-And-Match: A Novel Hybrid Tool for Enhancing Education and Research in
Rational Structure Based Drug Design.
AB - Rational drug design is the process of finding new medication that can activate
or inhibit the biofunction of a target molecule by binding to it and forming a
molecular complex. Here, shape and charge complementarities between drug and
target are key. To help find effective drug molecules out of a huge pool of
possibilities, physical and computer aided tools have been developed. Former
offers a tangible experience of the molecular interactions yet lacks measurement
and evaluation capabilities. Latter enables accurate and fast evaluations, but
does not deliver the interactive tangible experience of physical models. We
introduce a novel hybrid model called "Assemble-And-Match" where, we enhance and
combine the unique features of the two categories. Assemble-And-Match works based
on fabrication of customized molecular fragments using our developed software and
a 3D printer. Fragments are hinged to each other in different combinations and
form flexible peptide chains, conformable to tertiary structures, to fit in the
binding pocket of a (3D printed) target molecule. Through embedded measurement
marks, the molecular model is reconstructed in silico and its properties are
evaluated. We expect Assemble-And-Match tool can enable combination of
visuospatial perception with in silico computational power to aid research and
education in drug design.
PMID- 29339791
TI - The GluN2A Subunit Regulates Neuronal NMDA receptor-Induced Microglia-Neuron
Physical Interactions.
AB - Microglia are known to engage in physical interactions with neurons. However, our
understanding of the detailed mechanistic regulation of microglia-neuron
interactions is incomplete. Here, using high resolution two photon imaging, we
investigated the regulation of NMDA receptor-induced microglia-neuron physical
interactions. We found that the GluN2A inhibitor NVPAAM007, but not the GluN2B
inhibitor ifenprodil, blocked the occurrence of these interactions. Consistent
with the well-known developmental regulation of the GluN2A subunit, these
interactions are absent in neonatal tissues. Furthermore, consistent with a
preferential synaptic localization of GluN2A subunits, there is a differential
sensitivity of their occurrence between denser (stratum radiatum) and less dense
(stratum pyramidale) synaptic sub-regions of the CA1. Finally, consistent with
differentially expressed GluN2A subunits in the CA1 and DG areas of the
hippocampus, these interactions could not be elicited in the DG despite robust
microglial chemotactic capabilities. Together, these results enhance our
understanding of the mechanistic regulation of NMDA receptor-dependent microglia
neuronal physical interactions phenomena by the GluN2A subunit that may be
relevant in the mammalian brain during heightened glutamatergic neurotransmission
such as epilepsy and ischemic stroke.
PMID- 29339793
TI - Skin-inspired highly stretchable and conformable matrix networks for
multifunctional sensing.
AB - Mechanosensation electronics (or Electronic skin, e-skin) consists of
mechanically flexible and stretchable sensor networks that can detect and
quantify various stimuli to mimic the human somatosensory system, with the
sensations of touch, heat/cold, and pain in skin through various sensory
receptors and neural pathways. Here we present a skin-inspired highly stretchable
and conformable matrix network (SCMN) that successfully expands the e-skin
sensing functionality including but not limited to temperature, in-plane strain,
humidity, light, magnetic field, pressure, and proximity. The actualized specific
expandable sensor units integrated on a structured polyimide network, potentially
in three-dimensional (3D) integration scheme, can also fulfill simultaneous multi
stimulus sensing and achieve an adjustable sensing range and large-area
expandability. We further construct a personalized intelligent prosthesis and
demonstrate its use in real-time spatial pressure mapping and temperature
estimation. Looking forward, this SCMN has broader applications in humanoid
robotics, new prosthetics, human-machine interfaces, and health-monitoring
technologies.
PMID- 29339794
TI - HPV-16 virions can remain infectious for 2 weeks on senescent cells but require
cell cycle re-activation to allow virus entry.
AB - Successful infection with Human Papillomaviruses requires mitosis, when incoming
viral genomes gain access to nuclear components. However, very little is known
about how long HPV particles can remain infectious in non-dividing cells or in
which cellular compartments these viruses may reside. To investigate these
questions we have used BJ cells as a reversible model of senescence and show that
HPV-16 can only infect early-passage proliferating cells. Late-passage senescent
cells are resistant to HPV infection, but this can be reversed by inducing cell
cycle re-entry with a p53 siRNA. In senescent cells we find that efficient virus
entry can be attained upon cell cycle re-entry 16 days after infection,
demonstrating that HPV can persist for 2 weeks prior to induction of mitosis.
However, exposing cells to anti-HPV-16 L1 neutralising antibody blocks infection
at these late time points, suggesting that the virions reside near the cell
surface. Indeed, immunofluorescence analysis shows that virions accumulate on the
cell surface of senescent cells and only enter endocytic vesicles upon
stimulation with p53 siRNA. These results demonstrate that HPV-16 virions can
remain viable on a non-dividing cell for extended periods of time, but are
nonetheless vulnerable to antibody-induced neutralisation throughout.
PMID- 29339795
TI - Lipidized prolactin-releasing peptide improved glucose tolerance in metabolic
syndrome: Koletsky and spontaneously hypertensive rat study.
AB - BACKGROUND/OBJECTIVES: Prolactin-releasing peptide (PrRP) has a potential to
decrease food intake and ameliorate obesity, but is ineffective after peripheral
administration. We have previously shown that our novel lipidized analogs PrRP
enhances its stability in the circulation and enables its central effect after
peripheral application. The purpose of this study was to explore if sub-chronic
administration of novel PrRP analog palmitoylated in position 11 (palm11-PrRP31)
to Koletsky-spontaneously hypertensive obese rats (SHROB) could lower body weight
and glucose intolerance as well as other metabolic parameters. SUBJECTS/METHODS:
The SHROB rats (n = 16) were used for this study and age-matched hypertensive
lean SHR littermates (n = 16) served as controls. Palm11-PrRP31 was administered
intraperitoneally to SHR and SHROB (n = 8) at a dose of 5 mg/kg once-daily for 3
weeks. During the dosing period food intake and body weight were monitored. At
the end of the experiment the oral glucose tolerance test was performed; plasma
and tissue samples were collected. Thereafter, arterial blood pressure was
measured. RESULTS: At the end of the experiment, vehicle-treated SHROB rats
showed typical metabolic syndrome parameters, including obesity, glucose
intolerance, dyslipidemia, and hypertension. Peripheral treatment with palm11
PrRP31 progressively decreased the body weight of SHR rats but not SHROB rats,
though glucose tolerance was markedly improved in both strains. Moreover, in
SHROB palm11-PrRP31 ameliorated the HOMA index, insulin/glucagon ratio, and
increased insulin receptor substrate 1 and 2 expression in fat and insulin
signaling in the hypothalamus, while it had no effect on blood pressure.
CONCLUSIONS: We demonstrated that our new lipidized PrRP analog is capable of
improving glucose tolerance in obese SHROB rats after peripheral application,
suggesting that its effect on glucose metabolism is independent of leptin
signaling and body weight lowering. These data suggest that this analog has the
potential to be a compound with both anti-obesity and glucose-lowering
properties.
PMID- 29339796
TI - A user's guide to the ambiguous word 'epigenetics'.
PMID- 29339799
TI - Complementary therapies for fatigue after hematopoietic stem cell
transplantation: an integrative review.
AB - Fatigue after hematopoietic stem cell transplantation (HSCT) is a persistent
problem that limits activities and causes distress. Complementary therapies have
shown promising results in improving fatigue in several patient populations.
However, it is unknown whether they have the same effect on fatigue in the HSCT
population. This integrative review aimed to explore the literature that
evaluated complementary therapies for fatigue among HSCT patients. Only eight
studies were considered eligible for inclusion in this review. The eight studies
evaluated music therapy, relaxation, mindfulness, and massage techniques with
mixed results. These studies had major methodological limitations, such as the
small sample sizes and not blinding participants to the treatment allocation,
introducing possible bias. Furthermore, most of these studies used 'usual care'
control groups, leaving it unclear to what extent the observed effects are based
on the effects of complementary therapies, or rather on psychosocial factors such
as personal attention. More research is needed to more rigorously evaluate these
and other complementary therapies for the prevalent problem of fatigue in the
HSCT population.
PMID- 29339797
TI - A brave new world of RNA-binding proteins.
AB - RNA-binding proteins (RBPs) are typically thought of as proteins that bind RNA
through one or multiple globular RNA-binding domains (RBDs) and change the fate
or function of the bound RNAs. Several hundred such RBPs have been discovered and
investigated over the years. Recent proteome-wide studies have more than doubled
the number of proteins implicated in RNA binding and uncovered hundreds of
additional RBPs lacking conventional RBDs. In this Review, we discuss these new
RBPs and the emerging understanding of their unexpected modes of RNA binding,
which can be mediated by intrinsically disordered regions, protein-protein
interaction interfaces and enzymatic cores, among others. We also discuss the RNA
targets and molecular and cellular functions of the new RBPs, as well as the
possibility that some RBPs may be regulated by RNA rather than regulate RNA.
PMID- 29339800
TI - Haploidentical hematopoietic stem cell transplant for patients with sickle cell
disease using thiotepa, fludarabine, thymoglobulin, low dose cyclophosphamide,
200 cGy tbi and post transplant cyclophosphamide.
PMID- 29339798
TI - Shedding light on the cell biology of extracellular vesicles.
AB - Extracellular vesicles are a heterogeneous group of cell-derived membranous
structures comprising exosomes and microvesicles, which originate from the
endosomal system or which are shed from the plasma membrane, respectively. They
are present in biological fluids and are involved in multiple physiological and
pathological processes. Extracellular vesicles are now considered as an
additional mechanism for intercellular communication, allowing cells to exchange
proteins, lipids and genetic material. Knowledge of the cellular processes that
govern extracellular vesicle biology is essential to shed light on the
physiological and pathological functions of these vesicles as well as on clinical
applications involving their use and/or analysis. However, in this expanding
field, much remains unknown regarding the origin, biogenesis, secretion,
targeting and fate of these vesicles.
PMID- 29339802
TI - Biases of STRUCTURE software when exploring introduction routes of invasive
species.
AB - Population genetic methods are widely used to retrace the introduction routes of
invasive species. The unsupervised Bayesian clustering algorithm implemented in
STRUCTURE is amongst the most frequently used of these methods, but its ability
to provide reliable information about introduction routes has never been
assessed. We simulated microsatellite datasets to evaluate the extent to which
the results provided by STRUCTURE were misleading for the inference of
introduction routes. We focused on an invasion scenario involving one native and
two independently introduced populations, because it is the sole scenario that
can be rejected when obtaining a particular clustering with a STRUCTURE analysis
at K = 2 (two clusters). Results were classified as "misleading" or "non
misleading". We investigated the influence of effective size, bottleneck severity
and number of loci on the type and frequency of misleading results. We showed
that misleading STRUCTURE results were obtained for 10% of all simulated
datasets. Our results highlighted two categories of misleading output. The first
occurs when the native population has a low level of diversity. In this case, the
two introduced populations may be very similar, despite their independent
introduction histories. The second category results from convergence issues in
STRUCTURE for K = 2, with strong bottleneck severity and/or large numbers of loci
resulting in high levels of differentiation between the three populations.
Overall, the risk of being misled by STRUCTURE in the context of introduction
routes inferences is moderate, but it is important to remain cautious when low
genetic diversity or genuine multimodality between runs are involved.
PMID- 29339801
TI - Cardiac glycoside/aglycones inhibit HIV-1 gene expression by a mechanism
requiring MEK1/2-ERK1/2 signaling.
AB - The capacity of HIV-1 to develop resistance to current drugs calls for innovative
strategies to control this infection. We aimed at developing novel inhibitors of
HIV-1 replication by targeting viral RNA processing-a stage dependent on
conserved host processes. We previously reported that digoxin is a potent
inhibitor of this stage. Herein, we identify 12 other cardiac glycoside/aglycones
or cardiotonic steroids (CSs) that impede HIV growth in HIV-infected T cells from
clinical patients at IC50s (1.1-1.3 nM) that are 2-26 times below concentrations
used in patients with heart conditions. We subsequently demonstrate that CSs
inhibit HIV-1 gene expression in part through modulation of MEK1/2-ERK1/2
signaling via interaction with the Na+/K+-ATPase, independent of alterations in
intracellular Ca2+. Supporting this hypothesis, depletion of the Na+/K+-ATPase or
addition of a MEK1/2-ERK1/2 activator also impairs HIV-1 gene expression. Similar
to digoxin, all CSs tested induce oversplicing of HIV-1 RNAs, reducing unspliced
(Gag) and singly spliced RNAs (Env/p14-Tat) encoding essential HIV-1
structural/regulatory proteins. Furthermore, all CSs cause nuclear retention of
genomic/unspliced RNAs, supporting viral RNA processing as the underlying
mechanism for their disruption of HIV-1 replication. These findings call for
further in vivo validation and supports the targeting of cellular processes to
control HIV-1 infection.
PMID- 29339803
TI - Carbohydrates protect protein against abiotic fragmentation by soil minerals.
AB - The degradation and turnover of soil organic matter is an important part of
global carbon cycling and of particular importance with respect to attempts to
predict the response of ecosystems to global climate change. Thus, it is
important to mechanistically understand the processes by which organic matter can
be degraded in the soil environment, including contact with reactive or catalytic
mineral surfaces. We have characterized the outcome of the interaction of two
minerals, birnessite and kaolinite, with two disaccharides, cellobiose and
trehalose. These results show that birnessite reacts with and degrades the
carbohydrates, while kaolinite does not. The reaction of disaccharides with
birnessite produces Mn(II), indicating that degradation of the disaccharides is
the result of their oxidation by birnessite. Furthermore, we find that both
sugars can inhibit the degradation of a model protein by birnessite,
demonstrating that the presence of one organic constituent can impact abiotic
degradation of another. Therefore, both the reactivity of the mineral matrix and
the presence of certain organic constituents influence the outcomes of abiotic
degradation. These results suggest the possibility that microorganisms may be
able to control the functionality of exoenzymes through the concomitant excretion
of protective organic substances, such as those found in biofilms.
PMID- 29339805
TI - First description of behavior and immune system relationship in fish.
AB - Considering the intriguing relationship between immune system and behavior
recently described in mammals, and the lack of information of this relationship
in fish, here we describe for the first time the interaction between the immune
system and social and exploratory behavior in zebrafish. Fish high responders to
novelty (HRN) presented a proinflammatory profile, with increased IL-1beta and
reduced IL-10 expression compared to fish low responders to novelty (LRN).
Likewise, fish less responsive to social stimuli have a reduced expression of INF
gamma. We show that fish with different behavior patterns have differences in the
immune response. Our findings indicate that the interplay between immune system
and behavior in zebrafish is similar to that found in mammalian models and that
zebrafish should be considered as a potential model organism to study the
relationship between immune system and behavior.
PMID- 29339804
TI - EPHB6 and testosterone in concert regulate epinephrine release by adrenal gland
chromaffin cells.
AB - Erythropoietin-producing human hepatocellular receptor (EPH) B6 (EPHB6) is a
member of the receptor tyrosine kinase family. We previously demonstrated that
EPHB6 knockout reduces catecholamine secretion in male but not female mice, and
castration reverses this phenotype. We showed here that male EPHB6 knockout
adrenal gland chromaffin cells presented reduced acetylcholine-triggered Ca2+
influx. Such reduction depended on the non-genomic effect of testosterone.
Increased large conductance calcium-activated potassium channel current densities
were recorded in adrenal gland chromaffin cells from male EPHB6 knockout mice but
not from castrated knockout or female knockout mice. Blocking of the large
conductance calcium-activated potassium channel in adrenal gland chromaffin cells
from male knockout mice corrected their reduced Ca2+ influx. We conclude that the
absence of EPHB6 and the presence of testosterone would lead to augmented large
conductance calcium-activated potassium channel currents, which limit voltage
gated calcium channel opening in adrenal gland chromaffin cells. Consequently,
acetylcholine-triggered Ca2+ influx is reduced, leading to lower catecholamine
release in adrenal gland chromaffin cells from male knockout mice. This explains
the reduced resting-state blood catecholamine levels, and hence the blood
pressure, in male but not female EPHB6 knock mice. These findings have certain
clinical implications.
PMID- 29339806
TI - Tumor characteristics, treatments, and oncological outcomes of prostate cancer in
men aged <=50 years: a population-based study.
AB - BACKGROUND: To examine clinical characteristics, treatment modalities and
oncological outcomes of prostate cancer (PCa) according to young (<=50) vs. old
age. METHODS: Of 407,599 men with primary adenocarcinoma of the prostate within
the Surveillance, Epidemiology and End Results (SEER)-database (2004 to 2013),
18,387 were aged <=50 years (4.5%). Time trends, cumulative incidence, and
competing risks regression (CRR) analyses tested for differences between young
and old patients. Multi-variable analyses were adjusted for year of diagnosis,
race, marital status, Gleason Score, clinical tumor stage, and lymph node status.
RESULTS: Younger men had more favorable tumor characteristics: lower Gleason
Score, lower median PSA, and lower rates of metastases at diagnosis compared to
their older counterparts. Over time, no local treatment (NLT) rates increased,
radical prostatectomy (RP), and brachytherapy (BT) rates decreased and external
beam radiation (EBRT) rates remained unchanged. Moreover, the rate of de novo
metastatic prostate cancer increased in young patients from 2% (2004) to 3.2%
(2013) (p = 0.004). CRR models showed no difference in prostate cancer-specific
mortality (PCSM) between young and old, across all local treatment types.
CONCLUSIONS: Young PCa patients have more favorable disease characteristics at
presentation, are less frequently treated with RP or BT and more frequently
benefit of NLT. PCSM did not differ between young and old patients. However, it
is worrisome that recently more young PCa patients are diagnosed at a metastatic
stage.
PMID- 29339808
TI - Gut microbiota: Filling up on fibre for a healthy gut.
PMID- 29339807
TI - Overexpression of alpha (1,6) fucosyltransferase in the development of castration
resistant prostate cancer cells.
AB - Glycosylation is recognized as one of the most common modifications on proteins.
Recent studies have shown that aberrant expression of alpha (1,6)
fucosyltransferase (FUT8), which catalyzes the transfer of fucose from GDP-fucose
to core-GlcNAc of the N-linked glycoproteins, modulates cellular behavior that
could lead to the development of aggressive prostate cancer. While the
relationship between the abnormal expression of FUT8 and glycoprotein
fucosylation in different prostate cancer cells has been demonstrated, there is
no evidence that shows dysregulated fucosylation might be involved in prostate
cancer progression from androgen-dependent to castration-resistant prostate
cancer. In this study, using a proteomics approach, we analyzed androgen
dependent and androgen-resistant LAPC4 cells and identified FUT8 to be
significantly overexpressed in the androgen-resistant LAPC4 cells. These findings
were independently confirmed in LAPC4 cells that were treated with non-steroidal
anti-androgen (bicalutamide) and in the in vivo castrated tumor xenograft models.
Similarly, we also demonstrated that overexpression of FUT8 might be responsible
for the decreased PSA expression in prostate cancer specimens. To our knowledge,
this is the first study reporting the functional role of fucosylated enzyme in
the development of castration-resistant prostate cancer.
PMID- 29339809
TI - Gut microbiota: Targeting of specific microbial species mitigates colitis.
PMID- 29339811
TI - Diagnosis: Gas-sensing gut capsules.
PMID- 29339810
TI - Extrahepatic cancers and chronic HCV infection.
AB - Infectious agents, such as HCV, account for ~15% of human cancers. HCV infects
not only hepatocytes but also extrahepatic cells. Chronic HCV infection can
induce chronic inflammation with qualitative and quantitative alterations of the
immune repertoire and tissue microenvironment, which could induce various
neoplasias. Epidemiological studies and meta-analyses suggest an increased rate
of extrahepatic cancers in patients with chronic HCV infection along with a
higher risk of intrahepatic cholangiocarcinoma, pancreatic cancer and non-Hodgkin
lymphoma (NHL), highlighting the need to screen for HCV infection in patients
with these cancers. Development of B cell NHL has been associated with HCV
infection, with a relative risk of ~1.5. Direct transformation related to the
presence of the virus and chronic antigenic stimulation are the two major non
exclusive mechanisms involved in HCV-related lymphomagenesis. HCV infection
alters survival of patients with lymphoma, and sustained virologic response (SVR)
substantially improves prognosis. Antiviral treatments might induce remission of
indolent lymphoma when SVR is achieved even without chemotherapy, emphasizing the
role of HCV in lymphomagenesis in this context. However, studies are needed to
provide prospective evidence of a causal relationship between chronic HCV
infection and other extrahepatic cancers and to determine whether the risk of
extrahepatic cancers is reduced with SVR. In this Review, we report on recent
studies analysing the risk of extrahepatic cancers associated with chronic HCV
infection. Although there is no doubt regarding the direct and indirect causality
between HCV and NHL, an increased risk of other cancers is less clear, with the
exception of cholangiocarcinoma.
PMID- 29339812
TI - Colorectal cancer: Hand-in-hand - colorectal cancer metastasizes with
microorganisms.
PMID- 29339813
TI - A new group of synthetic phenolic-containing amphiphilic molecules for
multipurpose applications: Physico-chemical characterization and cell-toxicity
study.
AB - Nine synthetic amphiphilic phenolic lipids, varied in phenolic moiety
(caffeoyl/dimethylcaffeoyl) and fatty acid chain lengths (8-18) were
characterized by differential scanning calorimetry (DSC), temperature-ramp
Fourier transform infra-red spectroscopy (FT-IR) and atomic force microscopy
(AFM). FT-IR and DSC results revealed that the physical state and lateral packing
of synthetic molecules were largely governed by fatty acyls. The critical micelle
concentrations (CMC) of synthetic lipids was in the range of 0.1 mM to 2.5 mM,
affording generation of stable oil-in-water emulsions; as evidenced by the
creaming index (<5%) of emulsions stabilized by compounds C12-C16, and C12a-C16a
after 7 days' storage. AFM analysis revealed that compound C14 formed stable
double-layers films of 5.2 nm and 6.7 nm. Application studies showed that
formulations stabilized by synthesized compounds containing 30% fish oil had
superior physical and oxidative stability compared to formulations containing
commercial emulsifiers or their mixtures with phenolic acids. Moreover, the
synthetic compounds were non-toxic against in vitro transformed keratinocytes
from histologically normal skin and Caco-2 cell lines. This study demonstrates
the relevance of using a natural hydroxycarboxylic acid as a flexible linker
between natural antioxidants, glycerol and fatty acids to generate
multifunctional amphiphiles with potential applications in food, pharmaceutical
and cosmetic industry.
PMID- 29339814
TI - Long-lived hot-carrier light emission and large blue shift in formamidinium tin
triiodide perovskites.
AB - A long-lived hot carrier population is critical in order to develop working hot
carrier photovoltaic devices with efficiencies exceeding the Shockley-Queisser
limit. Here, we report photoluminescence from hot-carriers with unexpectedly long
lifetime (a few ns) in formamidinium tin triiodide. An unusual large blue shift
of the time-integrated photoluminescence with increasing excitation power (150
meV at 24 K and 75 meV at 293 K) is displayed. On the basis of the analysis of
energy-resolved and time-resolved photoluminescence, we posit that these
phenomena are associated with slow hot carrier relaxation and state-filling of
band edge states. These observations are both important for our understanding of
lead-free hybrid perovskites and for an eventual future development of efficient
lead-free perovskite photovoltaics.
PMID- 29339815
TI - MCL-1 is a prognostic indicator and drug target in breast cancer.
AB - Analysis of publicly available genomic and gene expression data demonstrates that
MCL1 expression is frequently elevated in breast cancer. Distinct from other pro
survival Bcl-2 family members, the short half-life of MCL-1 protein led us to
investigate MCL-1 protein expression in a breast cancer tissue microarray and
correlate this with clinical data. Here, we report associations between high MCL
1 and poor prognosis in specific subtypes of breast cancer including triple
negative breast cancer, an aggressive form that lacks targeted treatment options.
Deletion of MCL-1 in the mammary epithelium of genetically engineered mice
revealed an absolute requirement for MCL-1 in breast tumorigenesis. The clinical
applicability of these findings was tested through a combination of approaches
including knock-down or inhibition of MCL-1 to show triple-negative breast cancer
cell line dependence on MCL-1 in vitro and in vivo. Our data demonstrate that
high MCL-1 protein expression is associated with poor outcome in breast cancer
and support the therapeutic targeting of MCL-1 in this disease.
PMID- 29339816
TI - Dinuclear PhosphoiminoBINOL-Pd Container for Malononitrile: Catalytic Asymmetric
Double Mannich Reaction for Chiral 1,3-Diamine Synthesis.
AB - A phosphoiminoBINOL ligand was designed to form a dinuclear metal complex that
could hold a malononitrile molecule. The dinuclear bis(phosphoimino)binaphthoxy
Pd2(OAc)2 complex catalyzed a double Mannich reaction of N-Boc-imines with
malononitrile to give chiral 1,3-diamines with high enantioselectivity. The
rational asymmetric catalyst, which smoothly introduces the first coupling
product to the second coupling reaction while avoiding the reverse reaction,
facilitates the over-reaction into a productive reaction process.
PMID- 29339817
TI - Cooperating with machines.
AB - Since Alan Turing envisioned artificial intelligence, technical progress has
often been measured by the ability to defeat humans in zero-sum encounters (e.g.,
Chess, Poker, or Go). Less attention has been given to scenarios in which human
machine cooperation is beneficial but non-trivial, such as scenarios in which
human and machine preferences are neither fully aligned nor fully in conflict.
Cooperation does not require sheer computational power, but instead is
facilitated by intuition, cultural norms, emotions, signals, and pre-evolved
dispositions. Here, we develop an algorithm that combines a state-of-the-art
reinforcement-learning algorithm with mechanisms for signaling. We show that this
algorithm can cooperate with people and other algorithms at levels that rival
human cooperation in a variety of two-player repeated stochastic games. These
results indicate that general human-machine cooperation is achievable using a non
trivial, but ultimately simple, set of algorithmic mechanisms.
PMID- 29339818
TI - Development and optimization of a differentiated airway epithelial cell model of
the bovine respiratory tract.
AB - Cattle are subject to economically-important respiratory tract infections by
various bacterial and viral pathogens and there is an urgent need for the
development of more realistic in vitro models of the bovine respiratory tract to
improve our knowledge of disease pathogenesis. In the present study, we have
optimized the culture conditions in serum-free medium that allow bovine bronchial
epithelial cells (BBECs) grown at an air-liquid interface to differentiate into a
three-dimensional epithelium that is highly representative of the bovine airway.
Epidermal growth factor was required to trigger both proliferation and
differentiation of BBECs whilst retinoic acid was also essential for mucociliary
differentiation. Triiodothyronine was demonstrated not to be important for the
differentiation of BBECs. Oxygen concentration had a minimal effect although
optimal ciliation was achieved when BBECs were cultured at 14% oxygen tension.
Insert pore-density had a significant effect on the growth and differentiation of
BBECs; a high-pore-density was required to trigger optimum differentiation. The
established BBEC model will have wide-ranging applications for the study of
bacterial and viral infections of the bovine respiratory tract; it will
contribute to the development of improved vaccines and therapeutics and will
reduce the use of cattle in in vivo experimentation.
PMID- 29339819
TI - Ancient Human Migrations to and through Jammu Kashmir- India were not of Males
Exclusively.
AB - Jammu and Kashmir (J&K), the Northern most State of India, has been under
represented or altogether absent in most of the phylogenetic studies carried out
in literature, despite its strategic location in the Himalayan region.
Nonetheless, this region may have acted as a corridor to various migrations to
and from mainland India, Eurasia or northeast Asia. The belief goes that most of
the migrations post-late-Pleistocene were mainly male dominated, primarily
associated with population invasions, where female migration may thus have been
limited. To evaluate female-centered migration patterns in the region, we
sequenced 83 complete mitochondrial genomes of unrelated individuals belonging to
different ethnic groups from the state. We observed a high diversity in the
studied maternal lineages, identifying 19 new maternal sub-haplogroups (HGs).
High maternal diversity and our phylogenetic analyses suggest that the migrations
post-Pleistocene were not strictly paternal, as described in the literature.
These preliminary observations highlight the need to carry out an extensive study
of the endogamous populations of the region to unravel many facts and find links
in the peopling of India.
PMID- 29339820
TI - Histone Variant MacroH2A1 Plays an Isoform-Specific Role in Suppressing
Epithelial-Mesenchymal Transition.
AB - Epithelial-Mesenchymal Transition (EMT) is a biological program that plays key
roles in various developmental and pathological processes. Although much work has
been done on signaling pathways and transcription factors regulating EMT, the
epigenetic regulation of EMT remains not well understood. Histone variants have
been recognized as a key group of epigenetic regulators. Among them, macroH2A1 is
involved in stem cell reprogramming and cancer progression. We postulated that
macroH2A1 may play a role in EMT, a process involving reprogramming of cellular
states. In this study, we demonstrate that expression of macroH2A1 is
dramatically reduced during EMT induction in immortalized human mammary
epithelial cells (HMLE). Moreover, ectopic expression of the macroH2A1.1 isoform,
but not macroH2A1.2, can suppress EMT induction and reduce the stem-like cell
population in HMLE. Interestingly, macroH2A1.1 overexpression cannot revert
stable mesenchymal cells back to the epithelial state, suggesting a stage
specific role of macroH2A1.1 in EMT. We further pinpointed that the function of
macroH2A1.1 in EMT suppression is dependent on its ability to bind the NAD+
metabolite PAR, in agreement with the inability to suppress EMT by macroH2A1.2,
which lacks the PAR binding domain. Thus, our work discovered a previously
unrecognized isoform-specific function of macroH2A1 in regulating EMT induction.
PMID- 29339823
TI - Phosphate insensitive aminophosphonate mineralisation within oceanic nutrient
cycles.
AB - Many areas of the ocean are nutrient-poor yet support large microbial
populations, leading to intense competition for and recycling of nutrients.
Organic phosphonates are frequently found in marine waters, but require
specialist enzymes for catabolism. Previous studies have shown that the genes
that encode these enzymes in marine systems are under Pho regulon control and so
are repressed by inorganic phosphate. This has led to the conclusion that
phosphonates are recalcitrant in much of the ocean, where phosphorus is not
limiting despite the degradative genes being common throughout the marine
environment. Here we challenge this paradigm and show, for the first time, that
bacteria isolated from marine samples have the ability to mineralise 2
aminoethylphosphonate, the most common biogenic marine aminophosphonate, via
substrate-inducible gene regulation rather than via Pho-regulated metabolism.
Substrate-inducible, Pho-independent 2-aminoethylphosphonate catabolism therefore
represents a previously unrecognised component of the oceanic carbon, nitrogen
and phosphorus cycles.
PMID- 29339822
TI - Relationship between brachial-ankle and heart-femoral pulse wave velocities and
the rapid decline of kidney function.
AB - The impact of brachial-ankle pulse wave velocity (baPWV) and heart-femoral pulse
wave velocity (hfPWV) on rapid decline of estimated glomerular filtration rate
(eGFR) has been inconclusive. The database of a multicenter prospective study of
2238 patients in Korea enrolled from 2011 to 2016 was reviewed. After excluding
patients with missing baPWV (n = 257) and eGFR change (n = 180), the study
included 1801 non-dialysis chronic kidney disease (CKD) patients. The eGFR change
<-5ml/min/1.73 m2/year was defined as rapid decline. During a mean of 2.2 years,
the mean eGFR change was -3.6 ml/min/1.73 m2/year, and 31.6% of patients were
classified as having rapid decline. Older age, causes of CKD, increased heart
rate, systolic blood pressures, and proteinuria were associated with the highest
baPWV quintile. In multivariate logistic regression analyses, the odds of a rapid
decline in eGFR was 1.9 times higher in the fifth quintile than in the first
quintile (P = 0.013). In a subset with baPWV and hfPWV (n = 1182), high baPWV was
associated with rapid eGFR decline only when accompanied by a high hfPWV. These
findings suggest that central and peripheral PWVs may simultaneously affect rapid
eGFR decline.
PMID- 29339821
TI - Cigarette smoking is associated with an altered vaginal tract metabolomic
profile.
AB - Cigarette smoking has been associated with both the diagnosis of bacterial
vaginosis (BV) and a vaginal microbiota lacking protective Lactobacillus spp. As
the mechanism linking smoking with vaginal microbiota and BV is unclear, we
sought to compare the vaginal metabolomes of smokers and non-smokers (17
smokers/19 non-smokers). Metabolomic profiles were determined by gas and liquid
chromatography mass spectrometry in a cross-sectional study. Analysis of the 16S
rRNA gene populations revealed samples clustered into three community state types
(CSTs) ---- CST-I (L. crispatus-dominated), CST-III (L. iners-dominated) or CST
IV (low-Lactobacillus). We identified 607 metabolites, including 12 that differed
significantly (q-value < 0.05) between smokers and non-smokers. Nicotine, and the
breakdown metabolites cotinine and hydroxycotinine were substantially higher in
smokers, as expected. Among women categorized to CST-IV, biogenic amines,
including agmatine, cadaverine, putrescine, tryptamine and tyramine were
substantially higher in smokers, while dipeptides were lower in smokers. These
biogenic amines are known to affect the virulence of infective pathogens and
contribute to vaginal malodor. Our data suggest that cigarette smoking is
associated with differences in important vaginal metabolites, and women who
smoke, and particularly women who are also depauperate for Lactobacillus spp.,
may have increased susceptibilities to urogenital infections and increased
malodor.
PMID- 29339824
TI - Oral microbiota of periodontal health and disease and their changes after
nonsurgical periodontal therapy.
AB - This study examined the microbial diversity and community assembly of oral
microbiota in periodontal health and disease and after nonsurgical periodontal
treatment. The V4 region of 16S rRNA gene from DNA of 238 saliva and subgingival
samples of 21 healthy and 48 diseased subjects was amplified and sequenced. Among
1979 OTUs identified, 28 were overabundant in diseased plaque. Six of these taxa
were also overabundant in diseased saliva. Twelve OTUs were overabundant in
healthy plaque. There was a trend for disease-associated taxa to decrease and
health-associated taxa to increase after treatment with notable variations among
individual sites. Network analysis revealed modularity of the microbial
communities and identified several health- and disease-specific modules.
Ecological drift was a major factor that governed community turnovers in both
plaque and saliva. Dispersal limitation and homogeneous selection affected the
community assembly in plaque, with the additional contribution of homogenizing
dispersal for plaque within individuals. Homogeneous selection and dispersal
limitation played important roles, respectively, in healthy saliva and diseased
pre-treatment saliva between individuals. Our results revealed distinctions in
both taxa and assembly processes of oral microbiota between periodontal health
and disease. Furthermore, the community assembly analysis has identified
potentially effective approaches for managing periodontitis.
PMID- 29339826
TI - Using intracellular markers to identify a novel set of surface markers for live
cell purification from a heterogeneous hIPSC culture.
AB - Human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can
provide sources for midbrain dopaminergic (mDA) neural progenitors (NPCs) for
cell therapy to treat Parkinson's disease (PD) patients. However, the well-known
line-to-cell line variability in the differentiation capacity of individual cell
lines needs to be improved for the success of this therapy. To address this
issue, we sought to identify mDA NPC specific cell surface markers for
fluorescence activated cell sorting (FACS). Through RNA isolation after sorting
for NPCs based on staining for cell-specific transcription factors followed by
microarray, we identified two positive cell surface markers (CORIN and CD166) and
one negative cell surface marker (CXCR4) for mDA NPC sorting. These three markers
can enrich floor plate NPCs to 90% purity, and the sorted NPCs more efficiently
differentiate to mature dopaminergic neurons compared to unsorted or CORIN+ alone
mDA NPCs. This surface marker identification strategy can be used broadly to
facilitate isolation of cell subtypes of interest from heterogeneous cultures.
PMID- 29339825
TI - Corallivory and the microbial debacle in two branching scleractinians.
AB - The grazing activity by specific marine organisms represents a growing threat to
the survival of many scleractinian species. For example, the recent proliferation
of the corallivorous gastropod Drupella now constitutes a critical case in all
South-East Asian waters. If the damaging effects caused by this marine snail on
coral polyps are relatively well known, the indirect incidence of predation on
coral microbial associates is still obscure and might also potentially impair
coral health. In this study, we compared the main ecological traits of coral
associated bacterial and viral communities living in the mucus layer of Acropora
formosa and Acropora millepora, of healthy and predated individuals (i.e.,
colonized by Drupella rugosa), in the Bay of Van Phong (Vietnam). Our results
show a substantial impact of the gastropod on a variety of microbiological
markers. Colonized corals harbored much more abundant and active epibiotic
bacteria whose community composition shifted toward more pathogenic taxa
(belonging to the Vibrionales, Clostridiales, Campylobacterales, and
Alteromonadales orders), together with their specific phages. Viral epibionts
were also greatly influenced by Drupella corallivory with spectacular
modifications in their concentrations, life strategies, genotype richness, and
diversity. Novel and abundant circular Rep-encoding ssDNA viruses (CRESS-DNA
viruses) were detected and characterized in grazed corals and we propose that
their occurrence may serve as indicator of the coral health status. Finally, our
results reveal that corallivory can cause severe dysbiosis by altering virus
bacteria interactions in the mucus layer, and ultimately favoring the development
of local opportunistic infections.
PMID- 29339827
TI - The impact of SO2 on wine flavanols and indoles in relation to wine style and
age.
AB - Wine has one of the broadest chemical profiles, and the common oenological
practice of adding the antioxidant and antimicrobial sulfur dioxide has a major
impact on its metabolomic fingerprint. In this study, we investigated novel
discovered oenological reactions primarily occurring between wine metabolites and
sulfur dioxide. The sulfonated derivatives of epicatechin, procyanidin B2, indole
acetic acid, indole lactic acid and tryptophol were synthesized and for the first
time quantified in wine. Analysis of 32 metabolites in 195 commercial wines (1986
2016 vintages) suggested that sulfonation of tryptophan metabolites characterised
white wines, in contrast to red wines, where sulfonation of flavanols was
preferred. The chemical profile of the oldest wines was strongly characterised by
sulfonated flavanols and indoles, indicating that could be fundamental
metabolites in explaining quality in both red and white aged wines. These
findings offer new prospects for more precise use of sulfur dioxide in
winemaking.
PMID- 29339828
TI - Fish consumption and depression in Korean adults: the Korea National Health and
Nutrition Examination Survey, 2013-2015.
AB - BACKGROUND/OBJECTIVES: There is a growing body of evidence that supports the
potential role of fish consumption in relation to depression, but the data in
Korean population is scarce. Thus, we examined the association between fish
consumption and depression in Korean adults. SUBJECTS/METHODS: We conducted a
cross-sectional study in 9183 Korean adults aged 19-64 years who participated in
the 6TH Korea National Health and Nutrition Examination Survey (2013-2015), which
is a large nationally representative study of Korean population. Fish consumption
and depression status were assessed using questionnaires. Multivariable logistic
regression models were used to compute odds ratios (ORs) and 95% confidence
intervals (CIs) for physician-diagnosed clinical depression. RESULTS: Out of the
9183 subjects, 389 (4.2%) were diagnosed with depression. After adjusting for
potential confounders, the multivariable-adjusted ORs for clinical depression
across fish consumption were 1.00 (reference) for <1 time/week, 0.76 (95% CI:
0.56-1.04) for 1-3 times/week and 0.52 (95% CI: 0.37-0.74) for >=4 times/week (P
for trend = 0.0005). The inverse association for >=4 times/week of fish
consumption was stronger in women (OR = 0.44, 95% CI: 0.29-0.67, P for trend <
.0001), but there was no significant association in men. CONCLUSIONS: Our
findings suggest that high consumption of fish is associated with lower odds of
depression in Korean adults, particularly in women. These results warrant further
prospective studies to verify the association between fish consumption and risk
of depression in Korean adults.
PMID- 29339829
TI - Associations of the dietary approaches to stop hypertension (DASH) diet with
pregnancy complications in Project Viva.
AB - BACKGROUND/OBJECTIVES: The Dietary Approaches to Stop Hypertension (DASH) diet
has been shown to improve cardiometabolic outcomes in non-pregnant populations.
Little is known regarding the impact of this diet on health during pregnancy. The
objective of this research is to examine associations of adherence to the DASH
diet with hypertensive disorders of pregnancy (HDP) and other pregnancy outcomes.
SUBJECTS/METHODS: We conducted analyses with data that came from 1760 women in
Project Viva, a Boston-area longitudinal cohort recruited in early pregnancy 1999
2002. We derived a DASH score using data from a food frequency questionnaire
(FFQ) administered at median 11.1 weeks gestation. Next, we used multivariable
linear regression models that accounted for the woman's age at enrollment, pre
pregnancy body mass index (BMI), education, smoking habits, race/ethnicity,
gestational weight gain (GWG) up until the time of the FFQ, and total energy
intake to examine associations of the DASH score with HDP, gestational diabetes,
preterm delivery (<37 weeks), birth size, and GWG from FFQ to delivery. Models
for HDP and GDM were additionally mutually adjusted for each other. Because pre
pregnancy weight status may modify these relationships, we tested for
interactions between pre-pregnancy BMI and the DASH score. RESULTS: Mean +/- SD
age of the women was 32.2 +/- 4.9 years; 71.9% were white. Overall, the DASH diet
score (mean: 24.0, SD: 5.0) was not associated with any of the pregnancy outcomes
or complications. However, we found a positive association between the DASH diet
and subsequent GWG among women who were obese before pregnancy (0.19 [95% CI:
0.05, 0.34], P <= 0.05 kg higher GWG per 1 unit DASH score). CONCLUSIONS:
Adherence to DASH diet during early pregnancy does not appear to be protective
against HDP or other adverse pregnancy outcomes.
PMID- 29339830
TI - Differential association of dietary carbohydrate intake with metabolic syndrome
in the US and Korean adults: data from the 2007-2012 NHANES and KNHANES.
AB - BACKGROUND/OBJECTIVES: The risk factors for metabolic syndrome may differ between
Western and Asian countries due to their distinct dietary cultures. However, few
studies have directly compared macronutrient intake and its association with the
risk of metabolic syndrome in the US and Korean adults using national survey
data. SUBJECT/METHODS: Based on the data from the US and Korean versions of the
2007-2012 National Health and Nutrition Examination Survey (NHANES, KNHANES), a
total of 3,324 American and 20,515 Korean adults were included. In both
countries, dietary intake was measured using a 24-h dietary recall method and
metabolic syndrome was defined using the National Cholesterol Education Program
Adult Treatment Panel III criteria. RESULTS: The percentages of energy intake
from carbohydrate, protein, and fat were 50:16:33 in the US adults and 66:15:19
in the Korean adults. Regarding metabolic abnormalities, Korean adults in the
highest quintile of carbohydrate intake showed an increased risk of metabolic
syndrome in men and women, with abnormalities of reduced HDL cholesterol and
elevated triglyceride levels. In contrast, the US men showed no significant
association with metabolic syndrome and its abnormalities, while the US women
showed an increased risk of reduced HDL cholesterol and elevated triglycerides.
CONCLUSIONS: A high carbohydrate intake is associated with metabolic
abnormalities. As Korean adults consume more carbohydrate than American adults,
stronger associations of dietary carbohydrate with metabolic syndrome were
observed. Thus, further studies are necessary to elucidate the underlying
mechanisms of different contributors to developing metabolic disease in Western
and Asian populations.
PMID- 29339831
TI - Detection of antimicrobial resistance genes associated with the International
Space Station environmental surfaces.
AB - Antimicrobial resistance (AMR) is a global health issue. In an effort to minimize
this threat to astronauts, who may be immunocompromised and thus at a greater
risk of infection from antimicrobial resistant pathogens, a comprehensive study
of the ISS "resistome' was conducted. Using whole genome sequencing (WGS) and
disc diffusion antibiotic resistance assays, 9 biosafety level 2 organisms
isolated from the ISS were assessed for their antibiotic resistance. Molecular
analysis of AMR genes from 24 surface samples collected from the ISS during 3
different sampling events over a span of a year were analyzed with Ion AmpliSeqTM
and metagenomics. Disc diffusion assays showed that Enterobacter bugandensis
strains were resistant to all 9 antibiotics tested and Staphylococcus
haemolyticus being resistant to none. Ion AmpliSeqTM revealed that 123 AMR genes
were found, with those responsible for beta-lactam and trimethoprim resistance
being the most abundant and widespread. Using a variety of methods, the genes
involved in antimicrobial resistance have been examined for the first time from
the ISS. This information could lead to mitigation strategies to maintain
astronaut health during long duration space missions when return to Earth for
treatment is not possible.
PMID- 29339833
TI - The 'known-knowns', and 'known-unknowns' of extracellular Nm23-H1/NDPK proteins.
AB - Nucleoside diphosphate kinases (NDPKs/NDK/NME) are a multifunctional class of
proteins conserved throughout evolution. Whilst many of the functions of NDPKs
have been identified as intracellular, extracellular eukaryotic and prokaryotic
NDPK proteins are also detected in multiple systems and have been implicated in
both normal physiology and disease. This review provides an overview of where the
field stands on our developing understanding of how NDPK proteins get out of
cells, the physiological role of extracellular NDPKs, and how extracellular NDPKs
may signal to cells. We will also discuss some of the unanswered questions, the
'known-unknowns' that particularly warrant further investigation.
PMID- 29339832
TI - CLOCKDelta19 mutation modifies the manner of synchrony among oscillation neurons
in the suprachiasmatic nucleus.
AB - In mammals, the principal circadian oscillator exists in the hypothalamic
suprachiasmatic nucleus (SCN). In the SCN, CLOCK works as an essential component
of molecular circadian oscillation, and ClockDelta19 mutant mice show unique
characteristics of circadian rhythms such as extended free running periods,
amplitude attenuation, and high-magnitude phase-resetting responses. Here we
investigated what modifications occur in the spatiotemporal organization of clock
gene expression in the SCN of ClockDelta19 mutants. The cultured SCN, sampled
from neonatal homozygous ClockDelta19 mice on an ICR strain comprising
PERIOD2::LUCIFERASE, demonstrated that the Clock gene mutation not only extends
the circadian period, but also affects the spatial phase and period distribution
of circadian oscillations in the SCN. In addition, disruption of the
synchronization among neurons markedly attenuated the amplitude of the circadian
rhythm of individual oscillating neurons in the mutant SCN. Further, with
numerical simulations based on the present studies, the findings suggested that,
in the SCN of the ClockDelta19 mutant mice, stable oscillation was preserved by
the interaction among oscillating neurons, and that the orderly phase and period
distribution that makes a phase wave are dependent on the functionality of CLOCK.
PMID- 29339834
TI - Use of multicolor fluorescence in situ hybridization to detect deletions in
clinical tissue sections.
AB - A variety of laboratory methods are available for the detection of deletions of
tumor suppressor genes and losses of their proteins. The clinical utility of
fluorescence in situ hybridization (FISH) for the identification of deletions of
tumor suppressor genes has previously been limited by difficulties in the
interpretation of FISH signal patterns. The first deletion FISH assays using
formalin-fixed paraffin-embedded tissue sections had to deal with a significant
background level of signal losses affecting nuclei that are truncated by the
cutting process of slide preparation. Recently, more efficient probe designs,
incorporating probes adjacent to the tumor suppressor gene of interest, have
increased the accuracy of FISH deletion assays so that true chromosomal deletions
can be readily distinguished from the false signal losses caused by sectioning
artifacts. This mini-review discusses the importance of recurrent tumor
suppressor gene deletions in human cancer and reviews the common FISH methods
being used to detect the genomic losses encountered in clinical specimens. The
use of new probe designs to recognize truncation artifacts is illustrated with a
four-color PTEN FISH set optimized for prostate cancer tissue sections. Data are
presented to show that when section thickness is reduced, the frequency of signal
truncation losses is increased. We also provide some general guidelines that will
help pathologists and cytogeneticists run routine deletion FISH assays and
recognize sectioning artifacts. Finally, we summarize how recently developed
sequence-based approaches are being used to identify recurrent deletions using
small DNA samples from tumors.
PMID- 29339835
TI - Obtaining high quality transcriptome data from formalin-fixed, paraffin-embedded
diagnostic prostate tumor specimens.
AB - Prognostic genomic biomarkers that can be measured at diagnosis to aid choice of
treatment options are unavailable for most common cancers. This is due in part to
the poor quality and quantity of available diagnostic specimens for discovery
research and to limitations in genomic technologies. Recent technical advances
now enable high-density molecular analyses using suboptimal biological specimens.
Here we describe the optimization of a transcriptome-specific protocol for use
with formalin-fixed, paraffin-embedded (FFPE) diagnostic prostate cancer (PrCa)
specimens. We applied the Ion AmpliSeq Transcriptome Human Gene Expression Kit
(AmpliSeq Kit) to RNA samples extracted from 36 tumor-enriched and 16 adjacent
normal tissues (ADJNT) from 37 FFPE PrCa specimens over a series of eight pilot
studies, incorporating protocol modifications from Pilots 2 to 5. Data quality
were measured by (1) the total number of mapped reads; (2) the percentage of
reads that mapped to AmpliSeq target regions (OnTarget%); (3) the percentage of
genes on the AmpliSeq panel with a read count >=10 (TargetsDetected%); and (4)
comparing the gene read-count distribution of the prostate tissue samples with
the median gene read-count distribution of cell line-derived RNA samples.
Modifications incorporated into Pilot study 5 provided gene expression data
equivalent to cell line-derived RNA samples. These modifications included the use
of freshly cut slides for macrodissection; increased tissue section thickness (8
um); RNA extraction using the RecoverAll Total Nucleic Acid Isolation Kit for
FFPE (ThermoFisher); 18 target amplification cycles; and processing six samples
per Ion PI chip. This protocol will facilitate the discovery of prognostic
biomarkers for cancer by allowing researchers to exploit previously underutilized
diagnostic FFPE specimens.
PMID- 29339836
TI - The role of metabolic enzymes in mesenchymal tumors and tumor syndromes:
genetics, pathology, and molecular mechanisms.
AB - The discovery of mutations in genes encoding the metabolic enzymes isocitrate
dehydrogenase (IDH), succinate dehydrogenase (SDH), and fumarate hydratase (FH)
has expanded our understanding not only of altered metabolic pathways but also
epigenetic dysregulation in cancer. IDH1/2 mutations occur in enchondromas and
chondrosarcomas in patients with the non-hereditary enchondromatosis syndromes
Ollier disease and Maffucci syndrome and in sporadic tumors. IDH1/2 mutations
result in excess production of the oncometabolite (D)-2-hydroxyglutarate. In
contrast, SDH and FH act as tumor suppressors and genomic inactivation results in
succinate and fumarate accumulation, respectively. SDH deficiency may result from
germline SDHA, SDHB, SDHC, or SDHD mutations and is found in autosomal-dominant
familial paraganglioma/pheochromocytoma and Carney-Stratakis syndrome, describing
the combination of paraganglioma and gastrointestinal stromal tumor (GIST). In
contrast, patients with the non-hereditary Carney triad, including paraganglioma,
GIST, and pulmonary chondroma, usually lack germline SDH mutations and instead
show epigenetic SDH complex inactivation through SDHC promoter methylation.
Inactivating FH germline mutations are found in patients with hereditary
leiomyomatosis and renal cell cancer (HLRCC) syndrome comprising benign
cutaneous/uterine leiomyomas and renal cell carcinoma. Mutant IDH, SDH, and FH
share common inhibition of alpha-ketoglutarate-dependent oxygenases such as the
TET family of 5-methylcytosine hydroxylases preventing DNA demethylation, and
Jumonji domain histone demethylases increasing histone methylation, which
together inhibit cell differentiation. Ongoing studies aim to better characterize
these complex alterations in cancer, the different clinical phenotypes, and
variable penetrance of inherited and sporadic cancer predisposition syndromes. A
better understanding of the roles of metabolic enzymes in cancer may foster the
development of therapies that specifically target functional alterations in tumor
cells in the future. Here, the physiologic functions of these metabolic enzymes,
the mutational spectrum, and associated functional alterations will be discussed,
with a focus on mesenchymal tumor predisposition syndromes.
PMID- 29339837
TI - Validation of the Brief International Cognitive Assessment for Multiple Sclerosis
in Japan.
AB - Background: The Brief International Cognitive Assessment for MS (BICAMS) is a
practical battery for measuring cognitive function in multiple sclerosis (MS).
Objectives: We aimed to validate a Japanese version of the BICAMS in patients
with MS and healthy controls. Methods: The Symbol Digit Modalities Test (SDMT),
the California Verbal Learning Test-Second Edition (CVLT2) and the Brief
Visuospatial Memory Test Revised (BVMTR) were administered to 156 patients with
MS and 126 healthy controls (HCs). The BICAMS was re-administered in a subset of
27 MS patients and 30 HCs. Results: The mean (+/-SD) raw scores in the MS and HC
groups were as follows: SDMT: MS 47.9 +/- 14.0, HC 61.0 +/- 9.5; CVLT2: MS 48.6
+/- 12.6, HC 55.7 +/- 10.5; BVMTR: MS 23.5 +/- 8.4, HC 28.3 +/- 5.4,
respectively, and significant differences were found between the two groups on
all tests (p < 0.0001). Cohen's d values were 1.07, 0.60, and 0.67 in SDMT,
CVLT2, and BVMTR, respectively. The test-retest reliability coefficients for each
test were as follows: SDMT: r = 0.93; CVLT2: r = 0.82; and BVMTR: r = 0.77 (p <
0.0001). Conclusions: This study provides results that support the reliability
and validity of the BICAMS in Japan.
PMID- 29339838
TI - Force and Scale Dependence of the Elasticity of Self-Assembled DNA Bottle
Brushes.
AB - As a model system to study the elasticity of bottle-brush polymers, we here
introduce self-assembled DNA bottle brushes, consisting of a DNA main chain that
can be very long and still of precisely defined length, and precisely
monodisperse polypeptide side chains that are physically bound to the DNA main
chains. Polypeptide side chains have a diblock architecture, where one block is a
small archaeal nucleoid protein Sso7d that strongly binds to DNA. The other block
is a net neutral, hydrophilic random coil polypeptide with a length of exactly
798 amino acids. Light scattering shows that for saturated brushes the grafting
density is one side chain per 5.6 nm of DNA main chain. According to small-angle
X-ray scattering, the brush diameter is D = 17 nm. By analyzing configurations of
adsorbed DNA bottle brushes using AFM, we find that the effective persistence of
the saturated DNA bottle brushes is Peff = 95 nm, but from force-extension curves
of single DNA bottle brushes measured using optical tweezers we find Peff = 15
nm. The latter is equal to the value expected for DNA coated by the Sso7d binding
block alone. The apparent discrepancy between the two measurements is
rationalized in terms of the scale dependence of the bottle-brush elasticity
using theory previously developed to analyze the scale-dependent electrostatic
stiffening of DNA at low ionic strengths.
PMID- 29339839
TI - Trends in trauma-related mortality among adolescents: A 6 year snapshot from a
teaching hospital's post mortem data.
AB - Introduction: The aim is to explore the trends in trauma mortality in children
aged 0-18 years can help to co-ordinate resources toward research and programs to
reduce the burden. Methods: This is a retrospective study carried out on
adolescents <=18 years of age autopsied according to the attorney request at
Forensic Medicine & Toxicology department of King George's Medical University,
Lucknow, India in the period from January 1st, 2009 to December 31st, 2014.
Results: There were 9160 deaths from all causes in children <=18 years old, 7747
of which were due to trauma related causes, with a female predominance of 1.3:1.
The age distribution revealed that 65.8% of deaths occurred in the 10-18 age
group. Road traffic accidents (RTA) was the most prevalent cause (3635 deaths -
46.92%), followed by asphyxia (1128 deaths - 14.56%) and sexual assault (649
deaths - 8.37%). Asphyxia/suffocation was the major cause of injury with 31.96%
of deaths within group <1 year; asphyxia (28.66%) and transport-related injuries
(32.27%) were more predominant in the 1-4 age group; transport-related deaths
were frequent in the 5-9 age group (45.14%), 10-14 age group (55.68%) and in the
group 15-18 age group (51.69%). Regarding times of death, 61% occurred at the
scene, 5.6% during pre-hospital care, 26.2% occurred at the hospital within the
first 24 h after admission, and the remaining 7.6% of deaths occurred after 24 h
after admission to the hospital. When we analyzed the deaths according to the
intent, homicides occurred in 16% of cases. Unintentional injuries occurred in
69% of deaths and self-inflicted injuries were identified in 15% cases.
Conclusions: Findings show that there was a predominance of deaths in children
and adolescents males, between 15 and 18 years old, mainly from road traffic
accidents. This study highlights the burden of trauma caused mortalities in
children, which requires instant action.
PMID- 29339840
TI - Complex knee injury scenario in tertiary level care in North India: An
epidemiological study.
AB - : Floating knee injury has been considered as one of the severe orthopedic
injury, and is often associated with major systemic trauma involving other
organs. Objective: To identify the incidence of floating knee injury, severity of
injury and associated orthopaedic and non-orthopaedic injury. Methods:
Epidemiologic study conducted from 1 Jan 2014 to 31 Dec 2014. Results: A total of
136 cases with floating knee injury were registered. Modified Fraser
classification showed 58 patients had type 1, 74 had type 2 and 4 had type 3
floating knees. 119(87.5%) patients had open fractures and Gustilo-Anderson type
IIIA(29.4%) being the commonest. No Mortality was found. 16 (11.76%) of floating
knees had to undergo amputation of afflicted limb. Conclusion: Statics of such
data would be helpful in planning and preparing ourselves as healthcare
professionals to prevent high mortality and morbidity/disability in floating knee
injury. Study design: Retrospective Epidemiological. Level of Evidence: Level 4
(Case Study).
PMID- 29339841
TI - Role of autologous non-vascularised intramedullary fibular strut graft in humeral
shaft nonunions following failed plating.
AB - Background: Non-union humeral shaft fractures are seen frequently in clinical
practice at about 2-10% in conservative management and 30% in surgically operated
patients. Osteosynthesis using dynamic compression plate (DCP), intramedullary
nailing, locking compression plate (LCP), Ilizarov technique along with bone
grafting have been reported previously. In cases of prior failed plate-screw
osteosynthesis the resultant osteopenia, cortical defect, bone loss, scalloping
around screws and metallosis, make the management of non-union more complicated.
Fibular graft as an intramedullary strut is useful in these conditions by
increasing screw purchase, union and mechanical stability. This study is a
retrospective and prospective follow up of revision plating along with autologous
non-vascularised intramedullary fibular strut graft (ANVFG) for humeral non
unions following failed plate osteosynthesis. Materials and methods: Seventy
eight cases of nonunion humeral shaft fractures were managed in our institute
between 2008 and 2015. Of these, 57 cases were failed plate osteosynthesis, in
which 15 cases were infected and 42 cases were noninfected. Out of the 78 cases,
bone grafting was done in 55 cases. Fibular strut graft was used in 22 patients,
of which 4 cases were of primary nonunion with osteoporotic bone. Applying the
exclusion criteria of infection and inclusion criteria of failed plate
osteosynthesis managed with revision plating using either LCP or DCP and ANVFG,
17 cases were studied. The mean age of the patients was 40.11 yrs (range: 26-57
yrs). The mean duration of non-union was 4.43 yrs (range: 0.5-14 yrs). The mean
follow-up period was 33.41 months (range: 12-94 months). The average length of
fibula was 10.7 cm (range: 6-15 cm). Main outcome measurements included bony
union by radiographic assessment and pre- and postoperative functional evaluation
using the DASH (Disabilities of the Arm, Shoulder and Hand) score. Results:
Sixteen out of 17 fractures united following revision plating and fibular strut
grafting. Average time taken for union was 3.5 months (range: 3-5 months).
Complications included one each of implant failure with bending, transient radial
nerve palsy and transient ulnar nerve palsy. No case had infection, graft site
morbidity or peroneal nerve palsy. Functional assessment by DASH score improved
from 59.14 (range: 43.6-73.21) preoperatively to 23.39 (range: 8.03-34.2)
postoperatively (p = 0.0003). Conclusion: The results of our study indicate that
revision plating along with ANVFG is a reliable option in humeral diaphyseal non
unions with failed plate-screw osteosynthesis providing adequate screw purchase,
mechanical stability and high chances of union with good functional outcome.
PMID- 29339842
TI - The clinico-radiological outcome of open reduction and internal fixation of
displaced scaphoid fractures in the adult age group.
AB - Background: Scaphoid fracture is the most common among carpal bone fractures,
frequently imperceptible on initial radiographs. Tendency of scaphoid fracture to
undergo in non-union makes it an important challenging injury for all orthopaedic
surgeons. Displaced scaphoid fracture has high non-union rate in conservative
management asserting the need to explore operative treatment. Materials and
method: A prospective study was conducted in our institution in thirty patients
in 20 to 50 year age group, for displaced scaphoid fracture (<30 days duration).
Patient were followed up at every 4 week interval for 6 month and then three
monthly for total duration of 18 months. At each follow up clinical and
functional outcome was measured by Mayo wrist score and Patient rated wrist
evaluation, and radiological outcome was measured in terms of union. Results:
Mayo wrist score showed satisfactory outcome at 8 week, and good and excellent
outcome at 12 week and 16 week period. Patient rated wrist score showed
improvement in clinical and functional result at three month period. Conclusions:
The use of open reduction and internal fixation by Herbert screw in acute
displaced scaphoid fracture has good clinical, functional, and radiological
outcome, and associated with early recovery.
PMID- 29339843
TI - Distal radius re-fracture with bending of implant and neurovascular compromise.
AB - Peri-implant fractures of the wrist are uncommon, and usually present as stress
fractures distal to the site of the implant. We report an unusual case where the
radius has fractured beneath a plate, causing bending and deformity of the
implant. This prevented reduction of the fracture under sedation, so urgent
intervention became necessary due to neurovascular compromise.
PMID- 29339844
TI - The risk of deep vein thrombosis in total joint patients compared to orthopaedic
trauma patients: Need for new prevention guidelines.
AB - Background: The development of Deep Vein Thrombosis (DVT) is a major concern
following orthopaedic surgery. No study has yet to compare the rate and risk
factors for DVT between total joint and orthopaedic trauma patients. To evaluate
if DVT prophylaxis for trauma should differ from total joints, we explored the
rate and risk factors for DVT between both cohorts. Methods: Using a CPT code
search from 2005 to 2013 in the ACS-NSQIP database, 150,657 orthopaedic total
joint patients and 44,594 orthopaedic trauma patients were identified. DVT
complications, patient demographics, preoperative comorbidities, and surgical
characteristics were collected for each patient. A chi-squared test was used to
compare the risk factors for DVT between orthopaedic trauma and total joint
patients. A multivariable logistic regression model was built to adjust for
comorbidities for each cohort. Results: The rate of DVT diagnosis in the total
joint population was 0.8% (N = 1186) and 0.98% (N = 432) in the orthopaedic
trauma population (p = 0.57). After controlling for individual comorbidities,
dyspnea, peripheral vascular disease, and renal failure were significant risk
factors for DVT in total joint patients (p < 0.05), whereas age, ascites and
steroid use were significant risk factors for DVT in orthopaedic trauma patients
(p < 0.05). Conclusions: Historically, the risks for DVT in total joints have
been emphasized, yet based on our results, the incidence of DVT is the same for
orthopaedic trauma. However, the risk factors varied. It is therefore important
to consider specialty-specific DVT prophylaxis for orthopaedic trauma patients in
order to improve care and reduce postoperative complications.
PMID- 29339845
TI - Incidence of spinal fractures in the Netherlands 1997-2012.
AB - : : To determine time trends of emergency department (ED) visits, hospitalization
rates, spinal cord lesions and characteristics of patients with spinal fractures
in the Netherlands. METHODS: In an observational database study we used the Dutch
Injury Surveillance System to analyse spinal fracture-related ED visits,
hospitalization rates and spinal cord lesions between 1997 and 2012. RESULTS: The
total number of ED visits associated with spinal fractures increased from 4,507
in 1997 to 9,690 in 2012 (115% increase). The increase in the total number of
fractures occurred in all age groups independently of gender. However, incidence
rates increased more strongly with age and were higher in young males and ageing
females. The hospitalization rate of diagnosed spinal fractures remained stable
between 62 and 67%. The incidence of spinal cord lesions varied between 13.8 and
20.3 per million of the population over a period of 15 years. CONCLUSION: Spinal
fracture-related ED visits are increasing in the Dutch population, independently
of age or gender. The hospitalization rate and the absolute numbers of spinal
cord lesions have remained stable over a period of 15 years. These findings are
relevant for public health decision-making and resource allocation.
PMID- 29339846
TI - Ankle arthrodesis-Open versus arthroscopic: A systematic review and meta
analysis.
AB - Objectives: Our objective was to perform a systematic review of the literature
and conduct a meta-analysis to investigate the outcomes of open versus
arthroscopic methods of ankle fusion. Methods: In accordance with Preferred
Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement
standards, we performed a systematic review. Electronic databases MEDLINE,
EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials (CENTRAL)
were searched to identify randomised and non-randomised studies comparing
outcomes of arthroscopic and open ankle arthrodesis. The Newcastle-Ottawa scale
was used to assess the methodological quality and risk of bias of the selected
studies. Fixed-effect or random-effects models were applied to calculate pooled
outcome data. Results: We identified one prospective cohort study and 5
retrospective cohort studies, enrolling a total of 286 patients with ankle
arthritis. Our analysis showed that open ankle fusion was associated with a lower
fusion rate (OR 0.26, 95% CI 0.13-0.52, P = 0.0002), longer tourniquet time (MD
16.49, 95% CI 9.46-23.41, P < 0.00001), and longer length of stay (MD 1.60,95% CI
1.10-2.10, P < 0.00001) compared to arthroscopic ankle fusion; however, there was
no significant difference between two groups in terms of infection rate (OR 2.41,
95% CI 0.76-7.64, P = 0.14), overall complication rate (OR: 1.54, 95% CI 0.80
2.96, P = 0.20), and operation time (MD 4.09, 95% CI -2.49-10.66, P = 0.22). The
between-study heterogeneity was high for tourniquet time but low or moderate for
other outcomes. The direction of the effect sizes remains unchanged throughout
sensitivity analyses. Conclusions: The best available evidence demonstrates that
arthroscopic ankle fusion may be associated with a higher fusion rate, shorter
tourniquet time, and shorter length of stay compared to open ankle fusion. We
found no significant difference between two groups in terms of infection rate,
overall complication rate, and operation time. The best available evidence is not
adequately robust to make definitive conclusions. Long-term results of the
comparative efficacy of arthroscopic ankle fusion over open ankle fusion are not
currently available. Further high quality randomised controlled trials that are
adequately powered are required.
PMID- 29339847
TI - Giant extraskeletal osteochondroma of foot. A case report with review of
literature.
PMID- 29339848
TI - Habitual patellar dislocation in children: Results of surgical treatment by
modified four in one technique.
AB - Background: Habitual patellar dislocation is a rare condition affecting children.
The growth plates are open in children and any surgical intervention should take
that in to consideration. We are describing a modified four in one technique for
habitual patellar dislocation, which is a soft tissue procedure without the use
of any implant. Method: In this study we included 6 children (4 females and 2
males) with open growth plates, which were diagnosed with habitual patellar
dislocation. The average age of the patients were 9.6 years (range 5-13 years).
Our technique included lateral retinaculum release, vastus medialis obliques
(VMO) advancement, partial patellar tendon transposition and reconstruction of
medial patellofemoral ligament (MPFL). Patients were evaluated with Kujala
scoring pre and post operatively. The average follow up period was 12 months
(range 7-24 months). Results: There were no recurrence of patellar instability in
any of the cases. The mean Kujala score was 48 before surgery and it improved to
95 after 12 months of average follow-up after surgery. Conclusion: We conclude
that our method of treatment of habitual patellar dislocation by using modified
four in one technique in children with open physis reproduced excellent
functional outcome. It is simple, cheap and does not require any image guidance.
Therapeutic study: Level of evidence IV.
PMID- 29339849
TI - Can an exostosis be free floating without any continuity to the underlying bone:
A diagnostic dilemma.
AB - : Osteochondroma or exostosis is the most common primary bone tumor containing
both bone and cartilage. Soft tissue osteochondromas have been described at
various locations, however, to the best of our knowledge, there is only a single
case report of a soft tissue osteochondroma around the femoral neck. We, hereby
report second such case. CASE REPORT: A forty year old female presented with
swelling on medial aspect of left thigh since four years. Radiographs showed a
large mass at the inferior surface of the left femoral neck. CT scan revealed a
well defined lobulated mass lesion involving muscles of adductor compartment of
thigh. MRI showed lobulated periarticular, intramuscular, non enhancing lesion
isointense to the bone, but without any continuity to the adjacent femur.
Histopathology of the excised lesion turned out to be osteochondroma with origin
from soft tissue. This case highlights an important differential diagnosis to be
considered whenever an ossified mass is located in soft tissue.
PMID- 29339850
TI - Giant cell tumour of tendon sheath and synovial membrane: A review of 26 cases.
AB - Aim: Aim of our study is to highlight the incidence and benign nature of Giant
cell tumour of tendon sheath and need for complete removal, thus minimizing the
chances of recurrence. Material and methods: A total of 26 cases of Giant cell
tumour of tendon sheath operated in the department of Orthopaedics, Patna Medical
College & Hospital, Patna from 2003 to 2010 were included in this study. The
surgery was performed after clinical evaluation of the lesion and Fine Needle
Aspiration Cytology (FNAC). The tumour underwent en bloc marginal excision. The
patients were followed up for minimum two year. Results: Our study population
consisted of 18 females and 8 males. The mean age at the time of surgery was 38.3
years (range, 18-62 years). Twenty three cases were found in the 3rd and 4th
decade. Twenty two cases involved upper extremity and only 4 cases in lower
extremity. MRI was done in 2 cases where diagnosis was in doubt. Bony indentation
on X-ray film was found in 7 cases and thorough curettage of cortical shell was
done. All the cases were treated by marginal excision. Three cases developed post
operative stiffness but regained full range of movement with physiotherapy.
Sensory impairment was seen in 3 cases. Recurrence occurred in 2 case and they
were treated by repeat marginal excision. Conclusion: Meticulous en-masse
marginal excision of the giant cell tumour of tendon sheath in blood less field
using magnification is the treatment of choice.
PMID- 29339851
TI - Self-Report of Behaviors to Manage Neurogenic Bowel and Bladder by Individuals
with Chronic Spinal Cord Injury: Frequency and Associated Outcomes.
AB - Background: The management of neurogenic bowel and bladder by individuals with
spinal cord injury (SCI) often requires a complicated set of behaviors to
optimize functioning and reduce complications. However, limited research is
available to support the many recommendations that are made. Objective: To
describe the occurrence of behaviors associated with the management of neurogenic
bowel and bladder among individuals with chronic SCI and to explore whether
relationships exist between the performance of those behaviors and outcomes
related to health and quality of life. Methods: A survey was developed based on
clinical guidelines to collect self-report information about the performance of
specific behaviors associated with the management of neurogenic bowel and bladder
by individuals with SCI. It was administered to 246 individuals with chronic SCI
living in the community as part of a larger ongoing study. Results: Results
suggest that the methods that those with SCI use to manage neurogenic bowel and
bladder are multifaceted. Many methods are performed with significant
consistency, but significant variations exist for some and are often associated
with neurological status, methods of evacuation, and quality of life. Conclusion:
Many people with SCI of long duration are not sure of the sources of
recommendations for some of the management activities that they or their personal
care assistants conduct. It is prudent for clinicians working with these people
to review their recommendations periodically to ensure that they are current and
understood.
PMID- 29339852
TI - Resilience and Happiness After Spinal Cord Injury: A Qualitative Study.
AB - Objective: The purpose of this study was to identify factors associated with
resilience among individuals with spinal cord injury (SCI). Methods: Qualitative
analyses were conducted of the written comments that were completed as part of a
cross-sectional survey of individuals with SCI living in the community. More than
1,800 mail surveys were distributed to individuals identified as having a
traumatic SCI through the records and/or membership lists of 4 organizations.
Four hundred and seventy-five individuals completed and returned the survey, with
approximately half (48.6%; n = 231) of respondents answering the open-ended
question "Is there anything else you would like to tell us about your resilience
or ability to 'bounce back' when you face a challenge?" Results: Analyses of
these responses identified both specific resources and cognitive perspectives
that are associated with perceived happiness. Responses fell within 8 general
categories: resilience, general outlook on life, social support and social
relationships, religion or faith in a higher power, mood, physical health and
functioning (including pain), social comparisons, and resources. Nuanced themes
within these categories were identified and were generally concordant with self
reported level of happiness. Conclusion: A majority of respondents with SCI
identified themselves as happy and explained their adjustment and resilience as
related to personality, good social support, and a spiritual connection. In
contrast, pain and physical challenges appeared to be associated with limited
ability to bounce back.
PMID- 29339853
TI - Impact of Health Behaviors and Health Management on Employment After SCI:
Psychological Health and Health Management.
AB - Objective: The purpose of this study was to examine the relationship between
employment and psychological health and health management as described by
individuals with spinal cord injury (SCI) who were employed at least once
following injury. Methods: A qualitative approach used 6 focus groups at 2 sites
with 44 participants who were at least 10 years post SCI. All had been employed
at some point since injury. Heterogeneous and homogeneous groups were delineated
based on specific characteristics, such as education, gender, or race. Group
sessions followed a semi-structured interview format with questions about
personal, environmental, and policy related factors influencing employment
following SCI. All group sessions were recorded, transcribed, and coded into
conceptual categories to identify topics, themes, and patterns. Inferences were
drawn about their meaning. NVivo 10 software using the constant comparative
method was used for data analysis. Results: Narratives discussed the relationship
between employment and psychological and emotional health and health management.
Four themes were identified: (1) adjustment and dealing with emotional reactions,
(2) gaining self-confidence, (3) preventing burnout, and (4) attitudes and
perspectives. Most themes reflected issues that varied based on severity of
injury as well as stage of employment. Conclusions: Individuals with SCI who are
successful in working following injury must determine how to perform the
behaviors necessary to manage their health and prevent emotional or physical
complications. The emotional consequences of SCI must be recognized and addressed
and specific behaviors enacted in order to optimize employment outcomes.
PMID- 29339854
TI - Development and Feasibility of Health Mechanics: A Self-Management Program for
Individuals with Spinal Cord Injury.
AB - Objective: We conducted a pilot study to examine the feasibility of administering
an individual, in-person version of Health Mechanics, an innovative self
management program designed to teach individuals with spinal cord injury (SCI) to
maintain physical health and prevent secondary conditions. Methods: After
baseline assessments, 27 participants were randomized using a 2:1 block design to
either the experimental intervention or a usual care group. Thirteen of the 19
participants in the intervention group completed the program. Follow-up
assessments were completed at 3 and 6 months after baseline. Results: Results
suggest that the Health Mechanics intervention delivered in an in-person format
was perceived as useful and relevant in addressing a diverse range of health
issues with participants with a wide range of personal and impairment
characteristics. However, attrition rates and barriers to recruitment suggested
limitations in the acceptability of the format for this population. Conclusion:
Additional research is needed to identify the populations that would most benefit
from the program and the most efficacious context for administration.
PMID- 29339855
TI - Locomotor Training in the Pediatric Spinal Cord Injury Population: A Systematic
Review of the Literature.
AB - Background: The restoration of walking ability in the spinal cord injury (SCI)
population is an increasingly important goal in physical therapy. Locomotor
training (LT) is often implemented with the aim to restore ambulation. At this
point, there are no guidelines for LT in the pediatric SCI population.
Objectives: The aim of this review is to further narrow the effects of LT to the
pediatric SCI population and develop recommendations for pediatric LT. Methods: A
thorough search was performed using the following databases: Scopus, CINAHL,
PubMed, and Ovid. Studies were selected based on the following inclusion
criteria: pediatric SCI population, articles published within last 10 years,
human subjects, and LT. Studies looking at other neurological disorders and
subjects who were not previously ambulatory were excluded. Five students and one
Faculty Research Advisor from the university's Doctor of Physical Therapy Program
evaluated the inclusion criteria, conducted a risk of bias assessment using the
Downs and Black checklist, and extracted the results. Results: Six studies were
selected for this review. They showed gains in distance, gait speed, walking
independence, and participation. There were variations in results when comparing
gains in injury level based on the International Standards for Neurological
Classification of Spinal Cord Injury (ISNCSCI). Conclusions: Currently there is
insufficient evidence to determine the best clinical practice guidelines for
rehabilitation using LT within the pediatric SCI population.
PMID- 29339856
TI - Relationships Between Caregiver Characteristics and Health-Related Quality of
Life Among Youth with Spinal Cord Injury.
AB - Background: Past research has found a relationship between the mental health of
parental caregivers and their children with spinal cord injury (SCI), but little
is known about how other aspects of caregiver health and functioning impact
health-related quality of life (HRQOL) of youth. Objective: The purpose of this
study was to explore the importance of caregiver mental health, physical health,
burden, and problem-solving skills in relation to children's physical and
psychosocial HRQOL. Methods: Forty youths with SCI ages 7 to 17 years completed
the PedsQLTM; primary caregivers completed standardized measures of mental and
physical health, burden, and problem solving. We evaluated 2 hierarchical linear
regression models predicting children's physical and psychosocial HRQOL. Results:
The 40 youths were an average of 11.48 years (SD = 3.21), 62.5% were male, and
80% Caucasian. They had been injured an average of 6.90 years (SD = 3.92); 75%
had paraplegia, and 61.5% had complete injuries. Most caregivers were mothers
(85%), were married (60%), and had at least some college education (87.5%).
Univariate analyses revealed that caregiver problem solving alone was related to
children's physical HRQOL, and caregiver mental health, burden, and problem
solving were related to children's psychosocial HRQOL. Regression analyses
controlling for child age and injury level revealed effective caregiver problem
solving (P < .01) was significantly related to greater child physical (Model R2 =
0.440) and psychosocial (Model R2 = 0.547) HRQOL. Conclusions: Although
relationships should be explored longitudinally with larger samples, results
indicate caregiver problem solving may be a reasonable target for intervention to
improve HRQOL among youth with SCI.
PMID- 29339857
TI - Comparison of Soleus H-Reflexes in Two Groups of Individuals With Motor
Incomplete Spinal Cord Injury Walking With and Without a Walker.
AB - Objective: To compare phase- and task-dependent H-reflex modulation in standing
and walking in 2 spinal cord injury (SCI) groups with and without a walker.
Methods: Fourteen subjects with American Spinal Injury Association Impairment
Scale D SCI (40+/-10 years) participated. Tibial nerve was stimulated to evoke 15
H-reflexes (at M-wave 7%-13% of maximum-M). Results: H-reflex was greater in the
walker group during stance (but not standing/swing). Conclusion: Differences in H
reflex modulation between groups walking with and without a walker may be
explained by sensory mechanism that enhances central excitation, difference in
motor activation levels between groups, and other complex mechanisms that
influence balance or stability.
PMID- 29339858
TI - Examining How the Perception of Health Can Impact Participation and Autonomy
Among Adults with Spinal Cord Injury.
AB - Background: Studies examining participation as defined by the International
Classification of Functioning, Disability and Health (ICF) as well as autonomy
among the spinal cord injury population (SCI) are only starting to emerge. Little
research has looked at how this population perceives their health status and the
role this plays in active participation within their lives. Objective: This
exploratory study was developed to determine whether the perception of health has
an impact on participation and autonomy among adults with SCI. Methods: A
convenience sample of adults with SCI currently receiving outpatient services
from a rehabilitation hospital completed the online questionnaire. Forty-two
subjects responded and were categorized into 2 groups: Group 1, positive
perceived health, and Group 2, negative perceived health. The sample completed
the Impact on Autonomy and Participation (IPA) that has 5 subscales (autonomy
indoors, family role, autonomy outdoors, social life, and work/education) and
demographic questions. Results: Multivariate analysis of variance (MANOVA)
revealed that perceived health had a significant impact on family roles, autonomy
outdoors, social life, and work/education. Perceived health did not have a
significant impact on autonomy indoors. Conclusion: The perception of health may
have an impact on participation and autonomy within the areas of family role,
outdoors, work/education, and social life. Implications for rehabilitation are
included.
PMID- 29339859
TI - Life Space Assessment in Spinal Cord Injury.
AB - Objectives: To examine the Life Space Assessment (LSA) in persons with spinal
cord injury (SCI), exploring its psychometric properties, differences between
persons with cervical versus thoracolumbar injuries, and cutoff score
differentiating a restricted from an unrestricted life space. Method: We
conducted a test-retest reliability study in a community setting involving 50
persons with SCI (25 injured above C7, 25 injured below T1). Data were collected
in 2 phone interviews approximately 9 days apart using the LSA. Results: Mean LSA
scores were 66 +/- 25 (n = 50): 62 +/- 23 for the cervical group, and 70 +/- 25
for the thoracolumbar group. Scores were not significantly different between
phone interviews [t(49) = 0.379, p = .706] or between groups [t(48) = -1.214, p =
.231]. Test-retest reliability intraclass correlation coefficient (ICC) was 0.876
(95% CI, 0.792-0.928). Spearman's rho correlations between the LSA and
Reintegration to Normal Living Index total and subscores ranged from .509 to .538
(p < .001). LSA scores were normally distributed. The minimum detectable change
was approximately 23 points. A cutoff score of 78.5 (sensitivity 76.9%,
specificity 81.1%) differentiated between persons with a restricted from an
unrestricted life space if equipment and personal assistance were not needed for
mobility. If equipment was needed, the cutoff score was found to be 49
(sensitivity of 90%, specificity of 90%). Conclusions: The LSA is a reliable and
valid measure of life space in persons with SCI and can be used to identify
persons with a restricted life space who may be at increased risk of mobility
disability.
PMID- 29339860
TI - Early Access to Vocational Rehabilitation for Inpatients with Spinal Cord Injury:
A Qualitative Study of Patients' Perceptions.
AB - Background: A pilot early-intervention vocational rehabilitation program was
conducted in Sydney, Australia, over a 2-year period. It was postulated that the
early provision of integrated vocational rehabilitation services in the hospital
settings for newly injured individuals would be well received and result in
better employment and psychosocial health outcomes. Objective: The objective of
this qualitative inquiry was to examine the perspectives of program participants
who had completed the intervention about the timeliness, perceived value, and
critical elements of the early intervention. Methods: A convenience sample of
participants was selected by accessibility; participants were interviewed
individually after discharge using a semi-structured approach. Transcripts of the
interviews were created via audio recordings; interviews were transcribed
verbatim, and the contents were analyzed thematically. Results: Thirteen
participants aged from 19 to 60 years with varying levels of impairment and
vocational backgrounds were interviewed from 7 to 21 months post injury. Overall,
the early introduction of vocational rehabilitation services was well received
and viewed positively. Emerging themes include sense of direction and
distraction, advocacy, and support, with "hope" (early after injury) emerging as
the overarching theme. Criticisms voiced about the program were that it was
offered too early in the intensive care unit and there were competing interests
and information overload in the early recovery phase. Conclusions: Vocational
rehabilitation provided during inpatient rehabilitation appears appropriate,
important, and valuable from patients' perspective. Early engagement results in
feelings of hope and encourages patients to see the possibility of returning to
work or education very early after injury, and it allows rehabilitation to be
directed accordingly.
PMID- 29339861
TI - Perceptions of Shared Decision Making Among Patients with Spinal Cord
Injuries/Disorders.
AB - Background: Individuals with spinal cord injuries/disorders (SCI/D) are
interested in, and benefit from, shared decision making (SDM). Objective: To
explore SDM among individuals with SCI/D and how demographics and health and
SCI/D characteristics are related to SDM. Method: Individuals with SCI/D who were
at least 1 year post injury, resided in the Chicago metropolitan area, and
received SCI care at a Veterans Affairs (VA; n = 124) or an SCI Model Systems
facility (n = 326) completed a mailed survey measuring demographics, health and
SCI/D characteristics, physical and mental health status, and perceptions of
care, including SDM, using the Combined Outcome Measure for Risk Communication
and Treatment Decision-Making Effectiveness (COMRADE) that assesses decision
making effectiveness (effectiveness) and risk communication (communication).
Bivariate analyses and multiple linear regression were used to identify variables
associated with SDM. Results: Participants were mostly male (83%) and White (70%)
and were an average age of 54 years (SD = 14.3). Most had traumatic etiology, 44%
paraplegia, and 49% complete injury. Veteran/civilian status and demographics
were unrelated to scores. Bivariate analyses showed that individuals with
tetraplegia had better effectiveness scores than those with paraplegia. Better
effectiveness was correlated with better physical and mental health; better
communication was correlated with better mental health. Multiple linear
regressions showed that tetraplegia, better physical health, and better mental
health were associated with better effectiveness, and better mental health was
associated with better communication. Conclusion: SCI/D and health
characteristics were the only variables associated with SDM. Interventions to
increase engagement in SDM and provider attention to SDM may be beneficial,
especially for individuals with paraplegia or in poorer physical and mental
health.
PMID- 29339862
TI - Posttraumatic Stress Symptoms Among Spinal Cord Injury Patients in Trauma: A
Brief Report.
AB - Background: Attention has recently focused on posttraumatic stress disorder
(PTSD) among individuals with traumatic spinal cord injury (SCI). Purpose: To
examine characteristics of individuals with and without symptoms of PTSD
following acute SCI. Methods: Data were collected on 23 patients (age, 34.5 +/-
14.4 years) at a Level I trauma center (14.35 +/- 18.48 days following injury).
Results: There were 52.2% (n = 12) who experienced symptoms of PTSD post injury,
with a significant association in patients with a history of psychological
disorders (p = .0094). Conclusion: Findings suggest that patients with SCI who
present with PTSD symptoms in the acute trauma care settting should be provided
with specific cognitive behavioral interventions.
PMID- 29339864
TI - Current Management Strategies of Hydrocephalus in the Child With Open Spina
Bifida.
AB - Symptomatic hydrocephalus is a common condition associated with myelomeningocele
(open spina bifida). Traditionally, hydrocephalus was treated with insertion of a
ventriculo-peritoneal (VP) shunt. This has been the standard of treatment since
the introduction of the Holter shunt valve for the VP shunt in the late 1950s.
Now there are other treatments that offer alternatives to VP shunt diversion for
hydrocephalus. This article is a review of hydrocephalus associated with
myelomeningocele and its treatment options. Treatment in the form of a VP shunt,
endoscopic third ventriculostomy (ETV), and conservative management are
discussed.
PMID- 29339865
TI - Response of Scoliosis in Children with Myelomeningocele to Surgical Release of
Tethered Spinal Cord.
AB - Objective: To examine the effect of surgical tethered cord release (TCR) on
scoliosis in children with myelomeningocele. Methods: A retrospective review of
65 pediatric patients with myelomeningocele and TCR. The final sample consisted
of 20 patients with scoliosis who were managed conservatively after TCR. Results:
Average age at TCR was 6.2 years with average follow-up of 3.8 years. Scoliosis
of 1 (5%) patient improved, 7 (35%) were stable, and 12 (60%) worsened (>=10
degrees ). Fifty percent of patients ultimately required definitive spinal
surgery. TCR release delayed definitive spine surgery for an average of 3.2
years. Sixty-four percent of patients with curves less than or equal to 45
degrees had progression of their curves compared to 50% with curves greater than
45 degrees . For patients with curves less than or equal to 45 degrees , curves
progressed in 80% of those younger than 10 years as compared to 25% of those
older than 10 years. For patients with curves less than or equal to 45 degrees ,
43% required definitive spine surgery as opposed to 83% with curves greater than
45 degrees . Level of neurological involvement (ie, lumbar versus thoracic) and
age at untethering emerged as factors influencing the effects of TCR for patients
with curves less than or equal to 45 degrees . Lumbar curves had more favorable
results. Conclusion: Pediatric patients with myelomeningocele and scoliosis
should be closely assessed and monitored. A selective approach for youth with
lumbosacral level myelomeningocele and progressive curves less than or equal to
45 degrees may result in scoliosis stabilization and avoidance of definitive
surgery.
PMID- 29339863
TI - Prevention of Venous Thromboembolism in Individuals with Spinal Cord Injury:
Clinical Practice Guidelines for Health Care Providers, 3rd ed.: Consortium for
Spinal Cord Medicine.
PMID- 29339866
TI - ADHD and Attention Problems in Children With and Without Spina Bifida.
AB - Objectives: To identify differences in the diagnosis and treatment of attention
deficit/hyperactivity disorder (ADHD) between typically developing children and
children with spina bifida. Method: Sixty-eight children with spina bifida and 68
demographically matched, typically developing children participated in a larger,
longitudinal study. Rates of maternal, paternal, and teacher reports of attention
problems, as well as rates of maternal reports of ADHD diagnosis, diagnosing
provider, pharmaceutical treatment, mental health treatment, and academic
accommodations were obtained at 5 time points over a period of 8 years and were
compared across groups. Results: Children with spina bifida were more likely to
have an ADHD diagnosis and attention problems. Attention problems and ADHD
diagnoses were first reported at earlier time points for children with spina
bifida than typically developing children. Among children with ADHD or attention
problems, children with spina bifida were more likely to be treated with
medication, but they were just as likely to use mental health services and
receive resource services at school. Conclusions: Children with spina bifida were
diagnosed with ADHD and identified as having attention problems more frequently
and at an earlier age. This finding could be due to earlier symptom development,
greater parental awareness, or more contact with providers. Among those with ADHD
or attention problems, stimulant medication was more likely to be prescribed to
children with spina bifida, despite research that suggests it may not be as
beneficial for them. Further research on the effectiveness of ADHD
pharmacological treatment for children with spina bifida is recommended.
PMID- 29339867
TI - Does the CDC Definition of Fever Accurately Predict Inflammation and Infection in
Persons With SCI?
AB - Background: Pneumonia and septicemia have the greatest impact on reduced life
expectancy in persons with spinal cord injury (SCI). Fever is often the first
presenting symptom of infection or inflammation. Thermoregulatory dysfunction in
persons with SCI may preclude a typical febrile response to infection or
inflammation and thus delay diagnostic workup. Objective: To determine the core
temperature of persons with SCI in the setting of infection or inflammation and
the frequency with which it meets criteria for the CDC definition of fever
(>100.4 degrees F). Methods: Retrospective review of hospitalized SCI patients
over 5 years with a diagnosis of infection or inflammation (DI), defined by serum
leukocytosis. In this study, 458 persons with paraplegia (PP) and 483 persons
with tetraplegia (TP) had 4,191 DI episodes. Aural temperatures (Tau) on the day
of DI, 7 days prior, and 14 days afterwards were abstracted from medical records.
Main outcome measures were average Tau at DI, frequency of temperatures >100.4
degrees F at DI, and average baseline temperatures before and after DI. Results:
Average Tau at DI was 98.2 degrees F (+/-1.5) and 98.2 degrees F (+/-1.4) in the
TP and PP groups, respectively, with only 11.6% to 14% of DI resulting in Tau
>100.4 degrees F. Baseline temperatures ranged from 97.9 degrees F (+/-0.7) to
98.0 degrees F (+/-0.8). Conclusion: SCI persons with leukocytosis infrequently
mount a fever as defined by the CDC, and baseline temperatures were subnormal
(<98.6 degrees F). Thermoregulatory dysfunction likely accounts for these
findings. Tau >100.4 degrees F is not a sensitive predictor of infection or
inflammation in persons with SCI. Clinicians should be vigilant for alternative
symptoms of infection and inflammation in these patients, so diagnostic workup is
not delayed.
PMID- 29339868
TI - Feasibility and Acceptability of Implementing Indirect Calorimetry Into Routine
Clinical Care of Patients With Spinal Cord Injury.
AB - Background: In the absence of reliable predictive equations, indirect calorimetry
(IC) remains the gold standard for assessing energy requirements after spinal
cord injury (SCI), but it is typically confined to a research setting. The
purpose of this study is to assess the feasibility and acceptability of
implementing IC into routine clinical care in an Australian SCI rehabilitation
facility. Methods: Bedside IC (canopy hood) was performed, and patients completed
an IC acceptability questionnaire (open-ended; yes/no; 5-point Likert scale).
Fasted resting energy expenditure (REE) steady-state criteria were applied to
assess data quality, and adherence to a test >=20 minutes was recorded. Staff
were surveyed to assess impact of IC on usual care. Results: Of 35 eligible
patients, 9 declined (7 reported claustrophobia). One patient could not be tested
before discharge and 25 underwent IC (84% male, injury level C2-L2, AIS A-D).
Anxiety prevented one patient from completing IC, while another failed to fast.
The remaining 23 patients achieved a steady-state REE (>=5 consecutive minutes
with <=10% coefficient of variation for VO2 and VCO2). Test-retest (n = 5) showed
<10% variation in REE. Patients deemed the procedure acceptable, with 88%
reporting a willingness to repeat IC. Eighty percent of patients and 90% of staff
agreed it was acceptable for IC to be integrated into usual care. Conclusion:
This study found that IC is a feasible and acceptable addition to the routine
clinical care of patients recovering from SCI and may serve to improve accuracy
of nutrition interventions for this patient population.
PMID- 29339869
TI - Developing a Model of Care for Healing Pressure Ulcers With Electrical
Stimulation Therapy for Persons With Spinal Cord Injury.
AB - Background: Electrical stimulation therapy (EST) has been shown to be an
effective therapy for managing pressure ulcers in individuals with spinal cord
injury (SCI). However, there is a lack of uptake of this therapy, and it is often
not considered as a first-line treatment, particularly in the community.
Objective: To develop a pressure ulcer model of care that is adapted to the local
context by understanding the perceived barriers and facilitators to implementing
EST, and to describe key initial phases of the implementation process. Method:
Guided by the Knowledge-to-Action (KTA) and National Implementation Research
Network (NIRN) frameworks, a community-based participatory research (CBPR)
approach was used to complete key initial implementation processes including (a)
defining the practice, (b) identifying the barriers and facilitators to EST
implementation and organizing them into implementation drivers, and (c)
developing a model of care that is adapted to the local environment. Results: A
model of care for healing pressure ulcers with EST was developed for the local
environment while taking into account key implementation barriers including lack
of interdisciplinary collaboration and communication amongst providers between
and across settings, inadequate training and education, and lack of resources,
such as funding, time, and staff. Conclusions: Using established implementation
science frameworks with structured planning and engaging local stakeholders are
important exploratory steps to achieve a successful sustainable best practice
implementation project.
PMID- 29339870
TI - The Spinal Cord Outcomes Partnership Endeavor (SCOPE) SCI Clinical Trials Tables.
PMID- 29339871
TI - Foreword.
PMID- 29339872
TI - Neural Control and Physiology of Sexual Function: Effect of Spinal Cord Injury.
AB - Objective: To present the current understanding of normal anatomy, physiology,
sexual physiology, pathophysiology and the consequential sexual changes and
dysfunctions following a spinal cord injury (SCI). Methods: Narrative review of
the latest literature. Results: Peripheral innervations of the pelvis involve 3
sets of efferent neurons coordinated though the pelvic plexus (somatic,
thoracolumbar sympathetic, and sacral parasympathetic), and these are under
cerebral descending excitatory and inhibitory control. SCI, depending on the
level of lesion and completeness, can alter this cerebral control, affecting the
psychological and reflexogenic potential for genital arousal and also ejaculation
and orgasm. During arousal, nitric oxide is the main neurotransmitter for smooth
muscle relaxation in both male and female erectile tissue. In men, erection,
ejaculation, and orgasm are under separate neurological control and can be
individually affected by SCI. Conclusions: Since sexual function is rated amongst
the highest priorities by individuals living with SCI, methods employed to affect
the neurological changes to maximize sexual neurophysiology prior to initiating
medical therapies including paying attention to sexual sensate areas and visceral
signals with mindfulness techniques, practicing body mapping, and sexual
stimulation of sensate areas to encourage neuroplasticity. Attention should be
paid to the biopsychosocial sexual contexts within which persons with SCI live to
maximize their sexual and fertility rehabilitation.
PMID- 29339873
TI - Cardiovascular Physiology and Responses to Sexual Activity in Individuals Living
with Spinal Cord Injury.
AB - Background: Spinal cord injury (SCI) may profoundly impact autonomic function
producing a variable degree of dysfunction in cardiovascular, bronchopulmonary,
sweating, bladder, bowel, and sexual function. The cardiovascular system is
crucially important for sexual function, as it is responsible for blood flow
shifts to cavernous and musculoskeletal tissue during sexual activity. This
system is prone to 3 main abnormalities after SCI including low resting blood
pressure (LRBP), orthostatic hypotension (OH), and autonomic dysreflexia (AD),
all of which have important effects on sexual function. Methods: We review the
current etiological mechanisms and manifestations of cardiovascular dysfunction
after SCI and discuss how this is documented to impact sexual function in
individuals living with SCI. Conclusions: All individuals with SCI at or above
the T6 neurologic level have an increased risk of AD during sexual stimulation,
with increasing risk associated with higher levels of injury and greater
completeness of injury. AD can be silent, and individuals living with SCI should
be aware of blood pressure values at baseline and during sexual activity.
Clinicians performing vibrostimulation fertility procedures need to be aware of
the risk of AD and consider pretreatment if needed. Researchers studying the
cardiovascular response to sexual stimulation should consider continuous
monitoring of blood pressure, as intermittent monitoring may underestimate true
blood pressure values.
PMID- 29339874
TI - Women's Sexual Health and Reproductive Function After SCI.
AB - Sexual function and to a lesser extent reproduction are often disrupted in women
with spinal cord injuries (SCI), who must be educated to better understand their
sexual and reproductive health. Women with SCI are sexually active; they can use
psychogenic or reflexogenic stimulation to obtain sexual pleasure and orgasm.
Treatment should consider a holistic approach using autonomic standards to
describe remaining sexual function and to assess both genital function and
psychosocial factors. Assessment of genital function should include thoracolumbar
dermatomes, vulvar sensitivity (touch, pressure, vibration), and sacral reflexes.
Self-exploration should include not only clitoral stimulation, but also
stimulation of the vagina (G spot), cervix, and nipples conveyed by different
innervation sources. Treatments may consider PDE5 inhibitors and flibanserin on
an individual basis, and secondary consequences of SCI should address concerns
with spasticity, pain, incontinence, and side effects of medications.
Psychosocial issues must be addressed as possible contributors to sexual
dysfunctions (eg, lower self-esteem, past sexual history, depression, dating
habits). Pregnancy is possible for women with SCI; younger age at the time of
injury and at the time of pregnancy being significant predictors of successful
pregnancy, along with marital status, motor score, mobility, and occupational
scores. Pregnancy may decrease the level of functioning (eg, self-care,
ambulation, upper-extremity tasks), may involve complications (eg, decubitus
ulcers, weight gain, urological complications), and must be monitored for
postural hypotension and autonomic dysreflexia. Taking into consideration the
physical and psychosocial determinants of sexuality and childbearing allows women
with SCI to achieve positive sexual and reproductive health.
PMID- 29339875
TI - Reproductive Health of Men with Spinal Cord Injury.
AB - Most men with spinal cord injury (SCI) are infertile due to a combination of
erectile dysfunction, ejaculatory dysfunction, and abnormal semen quality. This
article addresses issues that should be considered when managing the reproductive
health of men with SCI. The authors present recommendations based on their
decades of experience in managing the reproductive health of more than 1,000 men
with SCI. Men with SCI face obstacles when pursuing sexual activity and/or
biologic fatherhood. Hypogonadism and premature symptoms of aging may interfere
with sexual function. Erectile dysfunction is prevalent in the SCI population,
and treatments for erectile dysfunction in the general population are also
effective in the SCI population. Most men with SCI cannot ejaculate with sexual
intercourse. The procedures of penile vibratory stimulation (PVS) and/or
electroejaculation (EEJ) are effective in obtaining an ejaculate from 97% of men
with SCI. The ejaculate often contains sufficient total motile sperm to consider
the assisted conception procedures of intrauterine insemination or even
intravaginal insemination at home. If PVS and/or EEJ fail, sperm may be retrieved
surgically from the testis or epididymis. Surgical sperm retrieval typically
yields enough motile sperm only for in vitro fertilization with intracytoplasmic
sperm injection. The majority of new cases of SCI occur in young men at the peak
of their reproductive health. With proper medical management, these men can
expect to experience active sexual lives and biologic fatherhood, if these are
their goals. Numerous tools are available to physicians for helping these
patients reach their goals.
PMID- 29339876
TI - Sexuality in Pediatric Spinal Cord Injury.
AB - Sexual development and sexuality in youth with pediatric spinal cord injury (SCI)
are critical areas clinicians must be aware of and discuss when working with
youth and their families. In addition to the general sexuality issues and
challenges of adolescence and adult development, youth with SCI face unique
physical and psychosocial issues. The goal of this article is to provide a
developmentally based discussion of sexuality in individuals with SCI from
infancy through emerging adulthood. An overview of psychosocial issues related to
sexual development and sexuality are presented for each stage of sexual
development along with recommendations for clinical practice, including patient
and caregiver education and counseling. In order to establish expectations for
youth with SCI, long-term outcomes related to sexuality and fertility of adults
with pediatric-onset SCI are presented.
PMID- 29339877
TI - A Multidisciplinary Approach to Sexual and Fertility Rehabilitation: The Sexual
Rehabilitation Framework.
AB - Many studies have identified improvement in sexual function as a priority for
persons with spinal cord injury (SCI). Due to the various secondary sensory,
motor, and autonomic consequences following SCI and due to the complexity of
sexuality per se, this area can be overwhelming to many health care
professionals. The literature indicate that sexual and fertility rehabilitation
must be addressed in a biopsychosocial manner and include various disciplines.
The multidisciplinary utilization of a Sexual Rehabilitation Framework (SRF)
allows the medical and/or psychosocial factors that impede or improve sexual and
reproductive function to be examined. The SRF is a user-friendly and simplified
way to proactively address the major biopsychosocial areas of sexuality and to
create a plan of action for the person with SCI. It is an adjunct tool to the
full sexual history, and it encourages all disciplines involved in SCI
rehabilitation to address the issue of sexual function in the same manner as they
would other activities of daily living. Eight areas are included in the SRF:
sexual drive/interest, sexual functioning, fertility and contraception, factors
associated with the condition, motor and sensory influences, bladder and bowel
influences, sexual self-view and self-esteem, and partnership issues. The use of
the SRF is encouraged in both inpatient and outpatient settings.
Multidisciplinary or interdisciplinary team work is encouraged in sexual and
fertility rehabilitation to move clinicians toward providing proactive and
comprehensive care for individuals with SCI or other chronic disabilities.
PMID- 29339878
TI - Improving Sexual Satisfaction in Persons with Spinal Cord Injuries: Collective
Wisdom.
AB - Sexuality is an important part of life, and it is necessary for clinicians to
have a specific format in which to address sexual issues with their patients. A
systematic approach to working with patients with spinal cord injury (SCI) to
improve their sexual functioning and response is presented. Nonjudgmental
communication about sexual concerns is followed by a detailed pre- and postinjury
medical, psychosocial, and sexual history. If preexisting sexual issues are
present, it is recommended that the patient be referred for assessment and
treatment of these separate from the patient's SCI-related concerns. Physical
examination, with special attention to issues that could impact the patient's
sexuality, is followed by a detailed neurologic assessment with specific
attention to the T11-L2 and S3-5 spinal segments. Education of the patient with
regard to his or her sexual potential and the need to be flexible in his or her
sexual repertoire is followed by self-exploration and practice. Routine follow-up
is suggested after patient's initial sexual exploration. Treatment of confounding
and iatrogenic factors related to SCI is followed by more sexual experience.
Afterwards the clinician is encouraged to use simple techniques to treat sexual
issues and follow-up with the patient to assess the outcome. A structured program
utilizing vibratory stimulation with or without midodrine is described as a way
to achieve ejaculation and potentially orgasm, and techniques for treating severe
autonomic dysreflexia are discussed. If these interventions do not alleviate the
patient's sexual concerns, the clinician should refer the patient for more
specialized consultation.
PMID- 29339879
TI - How Do Iranian People with Spinal Cord Injury Understand Marriage?
AB - Background: Spinal cord injury (SCI) is a life-altering experience. There is
little information about the perspectives of people with SCI toward marriage.
Purpose: To explore the understandings of Iranian adults with SCI about marriage.
Methods: In this qualitative inquiry, using a semi-structured interview guide, we
collected data from 53 single adults with SCI (41 men and 12 women) who were
referred to the Brain and Spinal Cord Injury Research Center, Tehran University
of Medical Sciences in Tehran. Barun and Clarke's thematic analysis approach was
applied for data analysis. Results: "Marriage" was thematized in outer and inner
scenarios. The outer scenario was explored in terms of physical disability
identified as a seminal determinant in successful marriage. "Attractiveness,"
"able body for breadwinning," "sexually active," and "reproduction" were dominant
concepts extracted from the participants' narratives. The participants' inner
scenarios revealed that marriage would be welcomed if a potential partner
accepted them as a "whole person" regardless of their SCI condition. Conclusion:
The findings suggest that adults with SCI do not ignore or reject marriage,
however it was not their life priority due to major concerns that they had
internalized. Considering the quality of care, people with SCI must be reassured
about their potential to get married. SCI-based sexuality education and
premarital counseling support the patients in their postmarital lives. Our
findings will provide decision makers and health providers with significant
insight for utilizing culturally appropriate services for people with SCI.
PMID- 29339881
TI - Erratum.
AB - [This corrects the article on p. 247 in vol. 22.].
PMID- 29339880
TI - Description of Urological Surveillance and Urologic Ultrasonography Outcomes in a
Cohort of Individuals with Long-Term Spinal Cord Injury.
AB - Background: Individuals with spinal cord injury (SCI) have an increased risk of
developing urological complications. Therefore, long-term routine urological
surveillance is recommended. Objective: To describe urological surveillance in
individuals with long-term SCI and to determine factors associated with urologic
ultrasonography (UU) outcome. Methods: Wheelchair-dependent individuals with an
SCI for 10 years or more were included. A medical assessment was done in 8
participating rehabilitation centers. The International Lower Urinary Tract
Function Basic SCI Data Set was used to assess bladder-emptying methods and
previous surgical procedures on the urinary tract. We studied urological
surveillance: whether participants had routine urological checkups (including UU)
and when latest urodynamic study was performed. Latest UU (performed <1 year ago)
was retrieved or, when lacking, UU was performed as part of our study. Results:
Median time since injury (TSI) was 22.0 years. Overall, 39% of the 282
participants did not have routine urological checkups and 33% never had a
urodynamic study performed. UU data (N = 243) revealed dilatation of the upper
urinary tract (UUT) in 4.5% of the participants and urinary stones in 5.7%.
Abnormal UU outcome was associated with increasing TSI, nontraumatic SCI, and
previous surgical bladder or UUT stone removal. UU outcome was not associated
with routine urological checkups or type of bladder-emptying method. Conclusions:
Over one-third of Dutch individuals with long-term SCI did not receive routine
urological surveillance. UU outcome was not associated with routine urological
checkups or type of bladder-emptying method. Further research on the indication
and frequency of urological surveillance is recommended.
PMID- 29339882
TI - Foreword.
PMID- 29339885
TI - Consumer Feedback to Steer the Future of Assistive Technology Research and
Development: A Pilot Study.
AB - Objective: The overall objective of this project was to identify consumers'
opinions of their needs and wants related to assistive technology (AT) in a
systematic and quantitative manner via a questionnaire that can be used to
validate existing and establish new research priorities. Methods: This pilot
study describes questionnaire development, online implementation, and revisions
considered to the questionnaire in preparation for conducting a nationwide
survey. Data from a sample (N = 112) are presented. The pilot study was critical
to refine the questions and ensure that meaningful information was being
collected. Results: It was identified that revisions were warranted to provide
more structure and allow for consumers to prioritize AT research efforts.
Conclusion: The questionnaire results, although positively in favor of many of
the technologies presented, are inconclusive to identify generalizable research
priorities, thus expansion to a nationwide population is warranted.
PMID- 29339886
TI - Step-Climbing Power Wheelchairs: A Literature Review.
AB - Background: Power wheelchairs capable of overcoming environmental barriers, such
as uneven terrain, curbs, or stairs, have been under development for more than a
decade. Method: We conducted a systematic review of the scientific and
engineering literature to identify these devices, and we provide brief
descriptions of the mechanism and method of operation for each. We also present
data comparing their capabilities in terms of step climbing and standard
wheelchair functions. Results: We found that all the devices presented allow for
traversal of obstacles that cannot be accomplished with traditional power
wheelchairs, but the slow speeds and small wheel diameters of some designs make
them only moderately effective in the basic area of efficient transport over
level ground and the size and configuration of some others limit maneuverability
in tight spaces. Conclusion: We propose that safety and performance test methods
more comprehensive than the International Organization for Standards (ISO)
testing protocols be developed for measuring the capabilities of advanced
wheelchairs with step-climbing and other environment-negotiating features to
allow comparison of their clinical effectiveness.
PMID- 29339887
TI - Kinematics and Stability Analysis of a Novel Power Wheelchair When Traversing
Architectural Barriers.
AB - Background: Electric-powered wheelchairs (EPWs) are essential devices for people
with disabilities for mobility and quality of life. However, the design of common
EPWs makes it challenging for users to overcome architectural barriers, such as
curbs and steep ramps. Current EPWs lack stability, which may lead to tipping the
EPW causing injury to the user. An alternative Mobility Enhancement Robotic
Wheelchair (MEBot), designed at the Human Engineering Research Laboratories
(HERL), was designed to improve the mobility of, and accessibility for, EPW users
in a wide variety of indoor and outdoor environments. Seat height and seat
inclination can be adjusted using pneumatic actuators connected to MEBot's 6
wheels. Method: This article discusses the design and development of MEBot,
including its kinematics, stability margin, and calculation of the center of mass
location when performing its mobility applications of curb climbing/descending
and attitude control. Motion capture cameras recorded the seat angle and joint
motion of the 6 wheel arms during the curb climbing/descending process. The
center of mass location was recorded over a force plate for different footprint
configurations. Results: Results showed that the area of the footprint changed
with the location of the wheels during the curb climbing/descending and attitude
control applications. The location of the center of mass moved +/-30 mm when the
user leaned sideways, and the seat roll and pitch angle were 0 degrees and +/
4.0 degrees , respectively, during curb climbing and descending. Conclusion:
Despite the user movement and seat angle change, MEBot maintained its stability
as the center of mass remained over the wheelchair footprint when performing its
mobility applications.
PMID- 29339888
TI - Integration of Pneumatic Technology in Powered Mobility Devices.
AB - Advances in electric motors, electronics, and control systems have enhanced the
capability and drivability of electric power mobility devices over the last 60
years. Yet, battery technologies used in powered mobility devices (PMDs) have not
kept pace. Recent advances in pneumatic technology, primarily the high torque,
low speed design of rotary piston air motors, directly align with the needs of
PMD. Pneumatic technology has advantages over battery-powered technology,
including lighter weight, lower operating costs, decreased environmental impact,
better reliability, and increased safety. Two prototypes were created that
incorporated rotary piston air motors, high-pressure air tanks, and air-pressure
regulators. Prototype 1 was created by modifying an existing electric PMD. Range
tests were performed to determine the feasibility of pneumatic technology and the
optimal combination of components to allow the longest range possible at
acceptable speeds over ideal conditions. Using a 1.44 L air tank for feasibility
testing, prototype 1 was capable of traveling 800 m, which confirmed the
feasibility of pneumatic technology usage in PMDs. Prototype 2 was designed based
on the testing results from prototype 1. After further optimization of prototype
2, the average maximum range was 3,150 m. Prototype 2 is up to 28.3% lighter than
an equivalent size electric PMD and can be fully recharged in approximately 2
minutes. It decreases the cost of PMDs by approximately $1,500, because batteries
do not need to be replaced over the lifetime of the device. The results provide
justification for the use of pneumatic technology in PMDs.
PMID- 29339889
TI - Performance Evaluation of a Mobile Touchscreen Interface for Assistive Robotic
Manipulators: A Pilot Study.
AB - Background: Assistive robotic manipulators (ARMs) have been developed to provide
enhanced assistance and independence in performance of daily activities among
people with spinal cord injury when a caregiver is not on site. However, the
current commercial ARM user interfaces (UIs) may be difficult to learn and
control. A touchscreen mobile UI was developed to overcome these challenges.
Objective: The object of this study was to evaluate the performance between 2 ARM
UIs, touchscreen and the original joystick, using an ARM evaluation tool (ARMET).
Methods: This is a pilot study of people with upper extremity impairments (N =
8). Participants were trained on 2 UIs, and then they chose one to use when
performing 3 tasks on the ARMET: flipping a toggle switch, pushing down a door
handle, and turning a knob. Task completion time, mean velocity, and open
interviews were the main outcome measurements. Results: Among 8 novice
participants, 7 chose the touchscreen UI and 1 chose the joystick UI. All
participants could complete the ARMET tasks independently. Use of the touchscreen
UI resulted in enhanced ARMET performance (higher mean moving speed and faster
task completion). Conclusions: Mobile ARM UIs demonstrated easier learning
experience, less physical effort, and better ARMET performance. The improved
performance, the accessibility, and lower physical effort suggested that the
touchscreen UI might be an efficient tool for the ARM users.
PMID- 29339890
TI - Further Development of a Robotic-Assisted Transfer Device.
AB - Background: The task of performing transfers, such as from a wheelchair to a bed,
has a high risk of injury to both the caregiver and the person being transferred.
Although mechanical transfer devices can reduce these risks, these devices are
not meant for use in the community and they still place strain on the caregiver
when used. Purpose: The aim of this study is to describe feedback gathered from
focus groups of potential users of the Robotic-Assisted Transfer Device (RATD)
and describe design changes aimed at preparing the device for the next step in
the development process. Method: The RATD was transferred to a newer electric
powered wheelchair (EPW), key components were redesigned, and the control program
was updated to increase the safety of the device. Two focus groups, one
consisting of people with disabilities and the other consisting of clinicians and
caregivers, were conducted to gather feedback from potential users. Results:
Error checking, safety zones, a motor brake, and a new track helped increase the
safety of the device. Sixty-three percent of the people with disabilities and 83%
of caregivers surveyed said they would use the device. Conclusions: The results
from the focus groups were positive and the design changes were successful, but
more development is needed before the RATD can be marketed.
PMID- 29339891
TI - Effect of Orthotic Gait Training with Isocentric Reciprocating Gait Orthosis on
Walking in Children with Myelomeningocele.
AB - Background: Mechanical orthoses are used to assist in standing and walking after
neurological injury in children with myelomeningocele (MMC). Objectives: To
evaluate the influence of orthotic gait training with an isocentric reciprocating
gait orthosis (IRGO) on the kinematics and temporal-spatial parameters of walking
in children with MMC. Methods: Five children with MMC were fitted with an IRGO.
They walked at their own comfortable cadence using the orthosis. The hip joint
angle, spatial temporal parameters, and compensatory motions were measured and
analyzed. Results: Significant increases in walking speed and step length were
demonstrated following orthotic gait training during walking with the IRGO. The
sagittal plane hip range of motion was also significantly increased; however, the
vertical and horizontal compensatory motions were significantly decreased.
Conclusion: This study evaluated the influence of gait training with an IRGO on
the kinematics and temporal spatial parameters in MMC children. The findings
showed that orthotic gait training improved hip joint range of motion, increased
walking speed and step length, and decreased lateral and vertical compensatory
motions during level-ground walking trials.
PMID- 29339892
TI - Care for Adults with Spina Bifida: Current State and Future Directions.
AB - The care for adults with spina bifida is an important area to study. As
increasing numbers of patients with spina bifida survive into adulthood, they
expect to thrive and receive the best possible care into adulthood to maintain
their health. Understanding the health needs in this emerging and changing
population will help clinicians provide the best anticipatory care for adults
with spina bifida and continue to improve outcomes. This will also impact
pediatric care by improving the ability to determine preventive methods from
early on and understand the impacts of pediatric care and decisions over the
lifespan.
PMID- 29339893
TI - Shoulder Functional Electrical Stimulation During Wheelchair Propulsion in Spinal
Cord Injury Subjects.
AB - Background: Subjects with spinal cord injury (SCI) propel their wheelchairs by
generating a different level of muscle activity given their multiple deficits in
muscle strength. Exercise training programs seem to be effective in improving
wheelchair propulsion capacity. Functional electrical stimulation (FES) therapy
is a complementary tool for rehabilitation programs. Objectives: To determine the
accuracy of the synchronization between the FES activation and the push phase of
the propulsion cycle by using hand pressure sensors that allow anterior deltoids
activation when the hand is in contact with the pushrim. Methods: We analyzed 2
subjects, with injuries at C6 American Spinal Injury Association Impairment Scale
(AIS) A and T12 AIS A. The stimulation parameters were set for a 30 Hz frequency
symmetrical biphasic wave, 300 MUs pulse width. Data were collected as
participants propelled the wheelchair over a 10-m section of smooth, level vinyl
floor. Subjects were evaluated in a motion analysis laboratory (ELITE; BTS,
Milan, Italy). Results: Subject 1 showed synchronization between the FES
activation and the push phase of 87.5% in the left hand and of 80% in the right
hand. Subject 2 showed synchronization of 95.1% in the left and of hand 94.9% in
the right hand. Conclusion: Our study determined a high accuracy of a novel FES
therapeutic option, showing the synchronization between the electrical
stimulation and the push phase of the propulsion cycle.
PMID- 29339894
TI - Exercise and Health-Related Risks of Physical Deconditioning After Spinal Cord
Injury.
AB - A sedentary lifestyle occurring soon after spinal cord injury (SCI) may be in
contrast to a preinjury history of active physical engagement and is thereafter
associated with profound physical deconditioning sustained throughout the
lifespan. This physical deconditioning contributes in varying degrees to lifelong
medical complications, including accelerated cardiovascular disease, insulin
resistance, osteopenia, and visceral obesity. Unlike persons without disability
for whom exercise is readily available and easily accomplished, exercise options
for persons with SCI are more limited. Depending on the level of injury, the
metabolic responses to acute exercise may also be less robust than those
accompanying exercise in persons without disability, the training benefits more
difficult to achieve, and the risks of ill-considered exercise both greater and
potentially irreversible. For exercise to ultimately promote benefit and not
impose additional impairment, an understanding of exercise opportunities and
risks if exercise is undertaken by those with SCI is important. The following
monograph will thus address common medical challenges experienced by persons with
SCI and typical modes and benefits of voluntary exercise conditioning.
PMID- 29339897
TI - Exploration of the Personal Health Record as a Tool for Spinal Cord Injury Health
Self-Management and Coordination of Care.
AB - Background: A personal health record (PHR) is a collection of electronic health
data drawn from multiple sources but managed by the patient. The PHR is a
strategy that enables patients to be proactive in the coordination of their care.
Objective: The purpose of this clinical improvement study was to discover what
worked, what did not work, and what could be improved in the initial
implementation of MyPHR, a PHR tailored to patients with spinal cord injury
(SCI), to make it a useful tool for care coordination and health self-management.
Methods: Five individuals with chronic (>1 year) SCI carried out trial use of
MyPHR. Twelve hours of interactions, including screen navigation and think-aloud
reflection, were recorded and analyzed using formative research, a qualitative
method and type of case study research. Results: Two key themes emerged to guide
the implementation of PHR technology: selectivity in the identification of
information for the patient to track, and continual support and communication
with the clinical team. Conclusion: Given the volume of electronic data available
to patients with SCI, the data identified to import, manage, and keep current in
a PHR have to be thoughtfully selected to make sure the patient is convinced of
the worth of this data record and is willing to invest the time and effort it
will take to maintain it. A PHR should be implemented with a deliberate focus on
its function as a tool that patients and providers use together to expand
communication as they work toward their common goal of optimizing health after
SCI.
PMID- 29339896
TI - Inflammatory Stress Effects on Health and Function After Spinal Cord Injury.
AB - Background: Injury to the spinal cord produces immediate, adaptive inflammatory
responses that can exacerbate the initial injury and lead to secondary damage.
Thus far, researchers and clinicians have focused on modulating acute
inflammation to preserve sensorimotor function. However, this singular approach
risks overlooking how chronic inflammation negatively impacts the broader health
of persons with a spinal cord injury (SCI). Objective: The aim of this monograph
was to discuss interrelated processes causing persistent inflammatory stress
after SCI, along with associated health risks. We review archetypal factors that
contribute to a chronic inflammatory state, including response to injury, acute
infection, and autonomic dysreflexia. Secondary complications producing and
exacerbating inflammation are also discussed, including pain, depression,
obesity, and injury to the integumentary and skeletal systems. Finally, we
discuss the role of bacteria and the gut microbiome in this process and then
conclude with a discussion on how a pro-inflammatory phenotype promotes an
elevated risk for cardiovascular disease after injury. Conclusions: Effectively
managing chronic inflammation should be a high priority for clinicians and
researchers who seek to improve the health and life quality of persons with SCI.
Chronic inflammation worsens secondary medical complications and amplifies the
risk for cardiometabolic disorders after injury, directly impacting both the
quality of life and mortality risk after SCI. Inflammation can worsen pain and
depression and even hinder neurological recovery. It is, therefore, imperative
that countermeasures to chronic inflammation are routinely considered from the
point of initial injury and proceeding throughout the lifespan of the individual
with SCI.
PMID- 29339898
TI - Overground Locomotor Training in Spinal Cord Injury: A Performance-Based
Framework.
AB - Background: Locomotor training (LT) is the most commonly used treatment to
improve walking performance following spinal cord injury (SCI). The advancement
of LT treatments requires the addition of integrative models accounting for the
numerous systems responsible for the recovery of walking function following SCI.
Objective: This perspective monograph aims to (a) describe a performance-based
framework for overground LT (OLT), (b) describe principles of adaptation and
motor learning used to inform OLT program design, and (c) present an example OLT
program based on the proposed framework. Methods: Individuals with chronic motor
incomplete SCI (7 male, 1 female) classified according to the American Spinal
Injury Association Impairment Scale (AIS) as C and D were included. OLT included
two 90-minute sessions performed over 12 weeks for a total of 24 sessions.
Outcomes measures included overground walking speed, walking economy, pulmonary
oxygen uptake, and muscle oxygen extraction measured via near-infrared
spectroscopy. Results: Preliminary findings demonstrate the potential of OLT, as
describe here, to increase overground walking speed, improve walking economy,
accelerate processes associated with oxygen delivery and utilization at the rest
to-work transition, and lower oxygen extraction requirements of skeletal muscle
during walking in individuals with chronic motor-incomplete SCI. Conclusion: The
proposed framework offers a valuable template for LT program design in both
clinical and research settings. Further research is necessary to better
understand the effects of OLT and how principles of specificity, progressive
overload, and variation within the performance-based framework can be manipulated
to maximize function, health, and quality of life in SCI.
PMID- 29339895
TI - Nutritional Health Considerations for Persons with Spinal Cord Injury.
AB - Chronic spinal cord injury (SCI) often results in morbidity and mortality due to
all-cause cardiovascular disease (CVD) and comorbid endocrine disorders. Several
component risk factors for CVD, described as the cardiometabolic syndrome (CMS),
are prevalent in SCI, with the individual risks of obesity and insulin resistance
known to advance the disease prognosis to a greater extent than other established
risks. Notably, adiposity and insulin resistance are attributed in large part to
a commonly observed maladaptive dietary/nutritional profile. Although there are
no evidence-based nutritional guidelines to address the CMS risk in SCI,
contemporary treatment strategies advocate more comprehensive lifestyle
management that includes sustained nutritional guidance as a necessary component
for overall health management. This monograph describes factors in SCI that
contribute to CMS risks, the current nutritional profile and its contribution to
CMS risks, and effective treatment strategies including the adaptability of the
Diabetes Prevention Program (DPP) to SCI. Establishing appropriate nutritional
guidelines and recommendations will play an important role in addressing the CMS
risks in SCI and preserving optimal long-term health.
PMID- 29339899
TI - Clinician-Focused Overview of Bionic Exoskeleton Use After Spinal Cord Injury.
AB - Spinal cord injury (SCI) resulting in paralysis of lower limbs and trunk
restricts daily upright activity, work capacity, and ambulation ability, putting
persons with an injury at greater risk of developing a myriad of secondary
medical issues. Time spent in the upright posture has been shown to decrease the
risk of these complications in SCI. Unfortunately, the majority of ambulation
assistive technologies are limited by inefficiencies such as high energy demand,
lengthy donning and doffing time, and poor gait pattern precluding widespread
use. These limitations spurred the development of bionic exoskeletons. These
devices are currently being used in rehabilitation settings for gait retraining,
and some have been approved for home use. This overview will address the current
state of available devices and their utility.
PMID- 29339900
TI - Exoskeleton Training May Improve Level of Physical Activity After Spinal Cord
Injury: A Case Series.
AB - Objectives: To determine whether the use of a powered exoskeleton can improve
parameters of physical activity as determined by walking time, stand up time, and
number of steps in persons with spinal cord injury (SCI). Methods: Three men with
complete (1 C5 AIS A and 2 T4 AIS A) and one man with incomplete (C5 AIS D) SCI
participated in a clinical rehabilitation program. In the training program, the
participants walked once weekly using a powered exoskeleton (Ekso) for
approximately 1 hour over the course of 10 to 15 weeks. Walking time, stand up
time, ratio of walking to stand up time, and number of steps were determined.
Oxygen uptake (L/min), energy expenditure, and body composition were measured in
one participant after training. Results: Over the course of 10 to 15 weeks, the
maximum walking time increased from 12 to 57 minutes and the number of steps
increased from 59 to 2,284 steps. At the end of the training, the 4 participants
were able to exercise for 26 to 59 minutes. For one participant, oxygen uptake
increased from 0.27 L/min during rest to 0.55 L/min during walking. Maximum
walking speed was 0.24 m/s, and delta energy expenditure increased by 1.4
kcal/min during walking. Body composition showed a modest decrease in absolute
fat mass in one participant. Conclusion: Exoskeleton training may improve
parameters of physical activity after SCI by increasing the number of steps and
walking time. Other benefits may include increasing energy expenditure and
improving the profile of body composition.
PMID- 29339901
TI - Influence of Reciprocating Link When Using an Isocentric Reciprocating Gait
Orthosis (IRGO) on Walking in Patients with Spinal Cord Injury: A Pilot Study.
AB - Background: Studies collectively imply that the reciprocal link has no effect on
walking when using reciprocating gait orthoses (RGOs). There may be differences
between the 2 configurations of the RGO (eg, isocentric reciprocating gait
orthosis [IRGO] and IRGO without reciprocating link), but the specific benefits
and problems encountered in their use must be understood. Purpose: To highlight
more evidence for the mechanical function of the reciprocal link in RGOs used for
walking by individuals with spinal cord injury (SCI). Methods: Nine people with
SCI participated in this study. Gait analysis was performed in 2 conditions
(walking with IRGO and walking with IRGO without reciprocating link) in a random
order. The Vicon digital capture system was used to obtain kinematic data.
Results: There were significant differences between each orthotic configuration
in terms of speed of walking (p = .029), step length (p = .048), hip joint range
of motion (ROM) (p <= .001), and lateral and vertical compensatory motions (p <=
.001). There was no significant difference between each orthotic configuration in
cadence (p = .162). Conclusion: The reciprocating link in IRGO improved the
walking parameters in SCI patients.
PMID- 29339902
TI - Study on the Effectiveness of Virtual Reality Game-Based Training on Balance and
Functional Performance in Individuals with Paraplegia.
AB - Objective: To determine whether there is any difference between virtual reality
game-based balance training and real-world task-specific balance training in
improving sitting balance and functional performance in individuals with
paraplegia. Methods: The study was a pre test-post test experimental design.
There were 30 participants (28 males, 2 females) with traumatic spinal cord
injury randomly assigned to 2 groups (group A and B). The levels of spinal injury
of the participants were between T6 and T12. The virtual reality game-based
balance training and real-world task-specific balance training were used as
interventions in groups A and B, respectively. The total duration of the
intervention was 4 weeks, with a frequency of 5 times a week; each training
session lasted 45 minutes. The outcome measures were modified Functional Reach
Test (mFRT), t-shirt test, and the self-care component of the Spinal Cord
Independence Measure-III (SCIM-III). Results: There was a significant difference
for time (p = .001) and Time * Group effect (p = .001) in mFRT scores, group
effect (p = .05) in t-shirt test scores, and time effect (p = .001) in the self
care component of SCIM-III. Conclusions: Virtual reality game-based training is
better in improving balance and functional performance in individuals with
paraplegia than real-world task-specific balance training.
PMID- 29339903
TI - Economic Consequences of an Implanted Neuroprosthesis in Subjects with Spinal
Cord Injury for Restoration of an Effective Cough.
AB - Objective: To determine if an implanted neuroprosthesis for restoration of an
effective cough is less costly than conventional methods of respiratory
management. Methods: Nonrandomized clinical trial of participants (N = 14) with
spinal cord injury (SCI) using the Cough Stimulator device in the inpatient
hospital setting for Cough Stimulator implantation and outpatient hospital or
residence for follow-up. A neuroprosthesis was implanted for restoration of an
effective cough. The annual costs associated with respiratory management, without
(pre implantation) and with (post implantation) the neuroprosthesis, were
examined over a 4-year period. Results: The total cost related to implantation of
the Cough Stimulator was $59,891, with no maintenance costs over subsequent
years. The incidence of respiratory tract infections and the need for caregiver
support fell significantly following implantation. The costs associated with
respiratory tract infections fell significantly from a mean of $36,406 +/-
11,855/year to $13,284 +/- 7,035/year (p < .05) pre and post implantation,
respectively. Costs fell further to $8,817 +/- 5,990 and $4,467 +/- 4,404
following the 2nd and 3rd years post implantation (p < .05), respectively. The
costs associated with caregiver support fell significantly from $25,312 +/-
8,019/year to $2,630 +/- 2,233/year (p < .05) pre and post implantation,
respectively, and remained low in subsequent years (p < .05). Other costs related
to secretion management fell significantly and remained low in subsequent years
(p < .05). Break-even analysis demonstrated that this point was reached in the
first year. Conclusion: The results of this investigation demonstrate that
implantation and use of the Cough Stimulator resulted in significant reductions
in the overall costs of respiratory management in this patient population.
PMID- 29339904
TI - Epidemiology of Pediatric Traumatic and Acquired Nontraumatic Spinal Cord Injury
in Ireland.
AB - Objective: To examine the epidemiology of pediatric traumatic (TSCI) and acquired
nontraumatic spinal cord injury (NTSCI) in Ireland. There are few studies
reporting pediatric TSCI incidence and fewer of pediatric NTSCI incidence,
although there are several case reports. As there is a single specialist
rehabilitation facility for these children, complete population-level data can be
obtained. Method: Retrospective review of prospectively gathered data in the
Patient Administration System of the National Rehabilitation Hospital of patients
age 15 years or younger at the time of SCI onset. Information was retrieved on
gender, age, etiology, level of injury/AIS. Population denominator was census
results from 1996, 2002, 2006, and 2011, rolled forward. Results: Since 2000, 22
children have sustained TSCI and 26 have sustained NTSCI. Median (IQR) age at
TSCI onset was 6.3 (4.4) years, and at NTSCI onset it was 7.3 (8.1) years. Most
common TSCI etiology was transportation (n = 10; 45.5%), followed by surgical
complications (n = 8; 36.4%); most common injury type was complete paraplegia (n
= 12; 54.5%) followed by incomplete paraplegia (n = 5; 22.7%). Most common NTSCI
etiology was transverse myelitis (n = 11; 42.3%) followed by vascular (n = 5;
20%); most common injury type was incomplete paraplegia (n = 17; 65.4%) followed
by incomplete tetraplegia (n = 6; 24%). Incidence of TSCI ranged from 0 to 3.1
per million per year; incidence of NTSCI ranged from 0 to 6.5 per million per
year. Conclusion: Incidence of SCI in Ireland seems similar to or slightly lower
than other developed countries. Injury patterns are also similar, considering
variations in reporting methods.
PMID- 29339905
TI - Review of the History of Non-traumatic Spinal Cord Dysfunction.
AB - Background: The incidence of non-traumatic spinal cord dysfunction (SCDys) is
reported to be higher than traumatic spinal cord injury (SCI) in many countries.
No formal review of the history of SCDys has been published. Objective: This
article aims to identify key highlights in the history of SCDys. Method: An
electronic literature search was conducted (January 2017) using MEDLINE (1946
2016) and Embase (1974-2016) databases for publications regarding the history of
SCDys. Publications on the history of SCI and a selection of neurology textbooks
and books on the history of neurology were reviewed for potentially relevant
references. The focus of the literature search was on identifying publications
that detail key highlights regarding the history of the diagnosis and management
of the most common SCDys conditions, as well as those of historical significance.
Results: The electronic search of MEDLINE and Embase identified 11 relevant
publications. The majority of publications included were identified from the
authors' libraries and a selection of books on neurology and the history of
neurology. Conclusions: This review outlines the history of SCDys, taking a
broader historical perspective and covering the increasing awareness of the role
of the spinal cord and knowledge of neuroanatomy. Key milestones in the history
of the diagnosis and management of the most common SCDys conditions are
presented. An appreciation of the history of SCDys increases our understanding of
the large number of people who contributed to our current knowledge of these
conditions and in some situations helps guide efforts regarding prevention of
SCDys.
PMID- 29339906
TI - Important Clinical Rehabilitation Principles Unique to People with Non-traumatic
Spinal Cord Dysfunction.
AB - Background: Non-traumatic spinal cord dysfunction (SCDys) is caused by a large
range of heterogeneous etiologies. Although most aspects of rehabilitation for
traumatic spinal cord injury and SCDys are the same, people with SCDys have some
unique rehabilitation issues. Purpose: This article presents an overview of
important clinical rehabilitation principles unique to SCDys. Methods: Electronic
literature search conducted (January 2017) using MEDLINE and Embase (1990-2016)
databases for publications regarding SCDys. The focus of the literature search
was on identifying publications that present suggestions regarding the clinical
rehabilitation of SCDys. Results: The electronic search of MEDLINE and Embase
identified no relevant publications, and the publications included were from the
authors' libraries. A number of important clinical rehabilitation principles
unique to people with SCDys were identified, including classification issues,
general rehabilitation issues, etiology-specific issues, and a role for the
rehabilitation physician as a diagnostic clinician. The classification issues
were regarding the etiology of SCDys and the International Standards for
Neurological Classification of Spinal Cord Injury. The general rehabilitation
issues were predicting survival, improvement, and rehabilitation outcomes;
admission to spinal rehabilitation units, including selection decision issues;
participation in rehabilitation; and secondary health conditions. The etiology
specific issues were for SCDys due to spinal cord degeneration, tumors, and
infections. Conclusions: Although there are special considerations regarding the
rehabilitation of people with SCDys, such as the potential for progression of the
underlying condition, functional improvement is typically significant with
adequate planning of rehabilitation programs and special attention regarding the
clinical condition of patients with SCDys.
PMID- 29339907
TI - Trends, Challenges, and Opportunities Regarding Research in Non-traumatic Spinal
Cord Dysfunction.
AB - Background: Spinal cord dysfunction (SCDys) is caused by heterogeneous health
conditions, and the incidence is increasing. Despite the growing interest in
rehabilitation research for SCDys, research into SCDys faces many challenges.
Objective: The objective of this project was to perform a clinical review of
changes in SCDys research over the last 4 decades; identify challenges to
conducting research in SCDys; and propose opportunities for improving research in
SCDys. Methods: A triangulation approach was used for obtaining evidence:
literature search (January 2017) using MEDLINE and Embase databases for
publications in English (1974-2016) regarding SCDys; workshop discussions at the
International Spinal Cord Society annual meeting, September 16, 2016, Vienna,
Austria; and our collective expertise in SCDys clinical rehabilitation research.
Results: There has been a substantial increase in publications on SCDys over the
4 decades, from 1,825 in 1974-1983 to 11,887 in the decade 2004-2013, along with
an improvement in research methodology. Numerous challenges to research in SCDys
rehabilitation were grouped into the following themes: (a) identification of
cases; (b) study design and data collection; and (c) funding, preclinical, and
international research. Opportunities for addressing these were identified.
Conclusions: The increase in scientific publications on SCDys highlights the
importance of this heterogeneous group among the research community. The overall
lack of good quality epidemiological studies regarding incidence, prevalence, and
survival in these patients serves as a benchmark for guiding improvements to
inform evidence-based care and policy.
PMID- 29339908
TI - Creation of an Algorithm to Identify Non-traumatic Spinal Cord Dysfunction
Patients in Canada Using Administrative Health Data.
AB - Background: The lack of consensus on the best methodology for identifying cases
of non-traumatic spinal cord dysfunction (NTSCD) in administrative health data
limits the ability to determine the burden of disease and provide evidence
informed services. Objective: The purpose of this study is to develop an
algorithm for identifying cases of NTSCD with Canadian health administrative
databases using a case-based approach. Method: Data were provided by the Canadian
Institute for Health Information that included all acute care hospital and day
surgery (Discharge Abstract Database), ambulatory (National Ambulatory Care
Reporting System), and inpatient rehabilitation records (National Rehabilitation
Reporting System) of patients with neurological impairment (paraplegia,
tetraplegia, and cauda equina syndrome) between April 1, 2004 and March 31, 2011.
The approach to identify cases of NTSCD involved using a combination of
diagnostic codes for neurological impairment and NTSCD etiology. Results: Of the
initial cohort of 23,703 patients with neurological impairment, we classified
6,362 as the "most likely NTSCD" group (had a most responsible diagnosis or pre
existing diagnosis of NTSCD and diagnosis of neurological impairment); 2,777 as
"probable NTSCD" defined as having a secondary diagnosis of NTSCD, and 11,179 as
"possible NTSCD" who had no NTSCD etiology diagnoses but neurological impairment
codes. Conclusion: The proposed algorithm identifies an inpatient NTSCD cohort
that is limited to patients with significant paralysis. This feasibility study is
the first in a series of 3 that has the potential to inform future research
initiatives to accurately determine the incidence and prevalence of NTSCD.
PMID- 29339909
TI - Validation of Algorithm to Identify Persons with Non-traumatic Spinal Cord
Dysfunction in Canada Using Administrative Health Data.
AB - Background: Administrative health data, such as the hospital Discharge Abstract
Database (DAD), can potentially be used to identify patients with non-traumatic
spinal cord dysfunction (NTSCD). Algorithms utilizing administrative health data
for this purpose should be validated before clinical use. Objective: To validate
an algorithm designed to identify patients with NTSCD through DAD. Method: DAD
between 2006 and 2016 for Southern Alberta in Canada were obtained through
Alberta Health Services. Cases of NTSCD were identified using the algorithm
designed by the research team. These were then validated by chart review using
electronic medical records where possible and paper records where electronic
records were unavailable. Measures of diagnostic accuracy including sensitivity,
specificity, and positive and negative predictive values and 95% confidence
intervals (CI) were computed. Results: Two hundred and eighty cases were
identified to have both the administrative codes for neurological impairments and
NTSCD etiology. Twenty-eight cases were excluded from analysis as 5 had
inadequate medical record information, 17 had traumatic spinal cord injury, and 6
were considered "other" non-spinal cord conditions. Measures of diagnostic
accuracy that were computed were sensitivity 97% (95% CI, 94%-98%), specificity
60% (95% CI, 47%-73%), positive predictive value (PPV) 92% (95% CI, 88%-95%), and
negative predictive value (NPV) 80% (95% CI, 65%-90%). The most prevalent
etiologies were degenerative (36.9%), infection (19.0%), oncology malignant
(15.1%), and vascular (10.3%). Conclusion: Our algorithm has high sensitivity and
PPV and satisfactory specificity and NPV for the identification of persons with
NTSCD using DAD, though the limitations for using this method should be
recognized.
PMID- 29339910
TI - Characteristics of Non-traumatic Spinal Cord Dysfunction in Canada Using
Administrative Health Data.
AB - Background: There is a paucity of studies using administrative health data to
examine the epidemiology, health care utilization, and outcomes for non-traumatic
spinal cord dysfunction (NTSCD). Objective: The purpose of this study is to
characterize discrete NTSCD cohorts using decision algorithms with Canadian
health administrative databases. Method: Data were provided by the Canadian
Institute for Health Information that included all acute care hospital, day
surgery, ambulatory, and inpatient rehabilitation records of patients with
neurological impairment between April 1, 2004 and March 31, 2011. Diagnostic
codes for neurological impairment and NTSCD etiology were used to identify cases
and classify 3 NTSCD groups (most likely, probable, and possible). Logistic
regression identified factors related to inpatient rehabilitation admission
within 7 days of discharge among the preferred group. Results: The most likely
NTSCD group (n = 6,362) was significantly older and had a greater proportion of
women and individuals with cauda equina lesions compared to the other 2 NTSCD
groups (probable [n = 2,777] and possible [n = 11,179]; ps < .001). Factors
associated with the likelihood of an inpatient rehabilitation admission included
being older (odds ratio [OR], 1.01; 95% CI, 1.00-1.01), being female (OR, 1.18;
95% CI, 1.06-1.32), having paraplegia diagnosis compared to cauda equina (OR,
1.24; 95% CI, 1.09-1.41), residing in an urban area compared to a rural area (OR,
1.34; 95% CI, 1.13-1.58), having degenerative etiology compared to other (OR,
1.59; 95% CI, 1.41-1.80), and having an MRI on record compared to not (OR = 1.57;
95% CI, 1.39-1.76). Conclusion: Administrative data allow for ongoing
surveillance of a population in a relatively cost-effective manner. Advancing our
knowledge of NTSCD epidemiology, health outcomes, and system performance can
inform policy and system planning.
PMID- 29339911
TI - Nature of the Non-traumatic Spinal Cord Injury Literature: A Systematic Review.
AB - Background: Non-traumatic SCI (NTSCI) etiologies represent a markedly
heterogeneous cluster of conditions defined within the consensus NTSCI taxonomy.
This meta-analysis assembles evidence about the occurrence of NTSCI and its
clinical outcomes with respect to 6 research domains. Purpose: To investigate the
quality and quantity of clinical NTSCI evidence published in the peer reviewed
literature with reference to prognosis, diagnosis, intervention, process of care,
methodology, and qualitative approaches. Methods: PubMed and MEDLINE OVID MeSH
heading searches were conducted for 5 common-language NTSCI descriptors. Filters
were English language and Entrez date (1997-2016). Filters also controlled for
case reports, editorials or errata, and invited reviews. NTSCI etiologies
incorrectly classified, animal studies, and multidimensional mapping studies were
excluded. Full texts were retrieved and ranked for evidence quality according to
PRISMA statement guidelines, or PEDro criteria. Data were extracted and simple
descriptive statistics applied. Results: The search terms non traumatic and non
traumatic SCI retrieved 282 articles, with 39 duplicates. After exclusion of 117
articles: Level 1V (60); NTSCI incorrectly evaluated (14); publication bias (2);
non-English language (1); and animal experiments (1), 126 titles/abstracts were
screened and ranked against criteria. Of the 8 papers allocated for full-text
review, a subset of 3 articles was ranked level 1A (1) or level 11A (2); mean
PEDro score 5.75+/-0.5. Reasons for full-text exclusions (5) were NTSCI
incorrectly classified (1) and statistical limitations (4). Of the 6 domains,
prognostics had adequate data yield (86) for evidence synthesis (4.8% ranked
level 1A, or 11A). Notable evidence gaps were identified in qualitative (1),
methodological (2), and diagnostic (8) domains. Conclusion: Therapeutic
approaches require an evidence-based understanding of the distinct contexts in
which NTSCI occurs, especially in less resourced settings. Our findings
underscore the need for qualitative and quantitative research on the occurrence
of NTSCI in all contexts.
PMID- 29339912
TI - Outcomes Following Ischemic Myelopathies and Traumatic Spinal Injury.
AB - Background: As the general population ages, the rising prevalence of vascular
lesions of the spinal cord will become significant. Purpose: The aim of this
study was to compare the neurological and functional outcomes of patients with
ischemic spinal cord injury (ISCI) and traumatic spinal cord injury (TSCI).
Methods: We conducted a retrospective study in a spinal cord unit of 2
rehabilitation hospitals. We studied 168 patients with a TSCI and 72 with an
ISCI. At admission and discharge, patients were evaluated by American Spinal
Injury Association Impairment Scale (AIS) standards and Spinal Cord Independence
Measure (SCIM). Length of stay, occurrence of complications, and discharge
dispositions were also recorded. Linear and logistic regression models were used
to analyze the effects of the etiology of the lesion, AIS level at admission, and
level of the lesion. Results: Patients with an ISCI were older and experienced
fewer cervical lesions and fewer complete lesions than patients with TSCI. By
linear and logistic regression, etiology was a predictor (together with lesion
features) of functional (SCIM improvement and SCIM at discharge) outcome, with
traumatic patients having better outcome than ischemic ones. Age, AIS level, and
lesion level were the chief predictors of length of stay, occurrence of
complications, and discharge dispositions. Conclusions: A diagnosis of ischemia
and trauma could be a determinant of functional recovery in SCI patients.
PMID- 29339913
TI - The Influence of Chronic Inflammation on Peripheral Motor Nerve Conduction
Following Spinal Cord Injury: A Randomized Clinical Trial.
AB - Objective: To examine the potential influence of chronic inflammation on
peripheral motor nerve function in vivo following spinal cord injury (SCI).
Methods: This study was part of a randomized, parallel-group, controlled clinical
trial. The study included 20 participants with varying levels and severities of
SCI randomized (3:2) to either a treatment group, consisting of a 12-week anti
inflammatory diet program, or control group. Outcome measures were assessed at
baseline, 1 month, and 3 months and consisted of measures of motor nerve
conduction velocity (NCV) and amplitude as well as markers of inflammation as
assessed by various pro- and anti-inflammatory cytokines. Results: Despite a
significant reduction in inflammation in the treatment group, 2-way repeated
measures analysis of variance (ANOVA) showed no significant Group * Time
interaction for motor NCV (p = .77) or M-wave amplitude (p = .61). Further, the
change in motor NCV and M-wave amplitude were not shown to be associated with the
change in inflammatory mediators as assessed via a backwards elimination multiple
regression analysis. Conclusion: These results suggest that at physiologically
relevant concentrations, inflammatory mediators may not have a substantial
influence on peripheral motor nerve conduction in vivo following SCI. Future
studies may still be warranted to examine the potential for central effects.
PMID- 29339914
TI - Perinatal Care for Women with Spinal Cord Injuries: A Collaborative Workshop for
Consensus on Care in Canada.
AB - Background: In North America, there are currently no clearly defined standards of
care for women with spinal cord injury (SCI) during the perinatal periods of
preconception, pregnancy, labour/delivery, and postpartum. Women with SCI and
their partners say resources specific to their needs are hard to find. Little
evidence-informed research exists to guide clinicians in the care of women with
SCI during pregnancy. Objectives: To further explore these gaps in knowledge and
practices for perinatal care for women with SCI, a 1-day workshop was held in
Vancouver, British Columbia (BC), Canada in November 2013. Methods: Twenty-nine
attendees included women with SCI, SCI-community service providers, researchers,
and health care providers from maternal/fetal medicine, rehabilitation,
anesthesiology, and psychiatry. A pre-meeting online survey of stakeholders
elucidated 3 themes: lack of knowledge for both consumers and care providers,
gaps in access to services and information, and a need for collaboration
throughout the perinatal journey. The workshop addressed issues of care
providers' lack of knowledge of nonmedical issues during the perinatal period,
physical and attitudinal barriers to access to care for women with SCI, and the
need for better collaboration and communication between care providers, the
latter potentially initiated by providing information to care providers through
the women with SCI themselves. Results: Content experts attending the workshop
collectively made recommendations for knowledge generation and research
priorities, clinical application priorities, and the need for policy and
guideline development in this field. Conclusion: Two information sources for
women have since been developed and are available online.
PMID- 29339915
TI - Minimal water-jet hydrodissection.
AB - This paper presents a hydrodissection technique performed with high-speed pulse
injection of only 0.1 cc liquid and assess its efficacy, safety, and the level of
reduction in posterior capsule rupture complications in phacoemulsification
cataract surgery. The kinetic energy of moving objects is directly proportional
to the mass and to the square of its velocity. The high energy obtained by high
speed pulse injection of a small amount of liquid ensures highly effective
dissection. Since the amount of liquid is very small, the increase in intraocular
pressure and the risk of rupture in the posterior capsule due to anterior
capsular block are greatly reduced. More importantly, several rotations of the
lens material in the capsule with effective hydrodissection facilitate the phases
of phacoemulsification and irrigation/aspiration. As most capsule ruptures occur
during these phases, the complication rate is thus reduced.
PMID- 29339916
TI - Pediatric cataract surgery with hydrophilic acrylic intraocular lens implantation
in Nepalese children.
AB - Purpose: To assess the outcome of cataract surgery with hydrophilic acrylic
intraocular lens (IOL) implantation in children with congenital and developmental
cataracts. Method: A retrospective review of medical records of children with
congenital or developmental cataracts who underwent cataract surgery with
hydrophilic IOL implantation, from January 2011 to December 2014 in a tertiary
eye hospital in Nepal. Primary posterior capsulotomy, anterior vitrectomy, and
IOL implantation was done in children 8 years or younger, while older children
underwent only lens aspiration and IOL implantation. Results: A total of 178 eyes
of 120 children underwent cataract surgery with primary IOL implantation. Mean
age at the time of surgery was 6.9 years (range: 3 months to 15 years). Average
follow-up time was 13.7 (+/-5.9) months. Associated ocular anomalies were present
in 84 (47.1%) eyes. Postoperative complications were found in 33 eyes (18.13%)
with inflammatory membrane being the most common (10.1%). Two eyes (1.1%)
developed endophthalmitis. Second intervention was needed in 12 (6.5%) eyes.
Preoperative vision of less than 6/60 was present in 105 eyes (57.69%). Final
best corrected visual acuity of 6/12 or better was found in 81 (44.5%) eyes.
Conclusion: Our study shows that hydrophilic IOL is suitable for use in children.
Results of this study are comparable with other studies on pediatric cataract
surgeries using hydrophobic acrylic intraocular lenses. Low cost hydrophilic lens
implantation is an effective approach in managing pediatric cataract surgery in
developing countries like Nepal.
PMID- 29339917
TI - Association of treatment adherence with real-life VA outcomes in AMD, DME, and
BRVO patients.
AB - Purpose: Real-life clinical outcomes of patients treated with anti-VEGF drugs for
neovascular age-related macular degeneration (nAMD), diabetic macular edema
(DME), or macular edema secondary to branch retinal vein occlusion (BRVO) are
often inferior to results from randomized clinical trials. This observational
cohort study investigates treatment adherence and real-life clinical outcomes
within the first year of treatment. Patients and methods: A total of 708
treatment-naive patients (466 nAMD, 134 DME, and 108 BRVO) were included.
Patients were followed with a PRN treatment protocol with three intravitreal
injections (IVIs) and a series of 3 monthly injections in case of persistent or
recurrent disease activity, as determined by monthly follow-up exams including
optical coherence tomographies. Occurrence of gaps of >56 days between treatments
or follow-up (nonadherence [NA]) and the reasons for NA (patient- or center
associated) as well as disease activity within the first 12 months of treatment
were analyzed. Visual acuity (VA) as well as numbers and dates of optical
coherence tomography and IVI were extracted from medical records. Results: NA
occurred significantly more often in patients with DME (44%) than nAMD (32%) or
BRVO (25%, p<0.01 between groups). NA was mainly patient-associated (nAMD: 80.0%,
DME: 83.1%, BRVO: 70.4%, p=0.38 between groups). Patients with nAMD and DME and
appropriate treatment/follow-up adherence had a better chance of significantly
gaining or maintaining VA, respectively (19.9% vs 12.0% with 3-line-gain in nAMD
and 1.3% vs 15.3% 3-line loss in DME; each p<0.05). NA did not correlate with VA
outcomes in BRVO (3-line gain 30.9% vs 48.1% and 3-line loss 8.6% vs 7.4%;
p>0.05). Conclusion: NA to treatment and follow-up regimens is a common problem
in the management of patients with AMD and DME and limits clinical treatment
outcomes under real-life conditions. Patients with DME have the highest risk of
patient-associated NA, associated with a higher risk for significant VA loss.
PMID- 29339918
TI - Comparability and repeatability of different methods of corneal astigmatism
assessment.
AB - Purpose: To assess the comparability and repeatability of keratometric and
astigmatism values measured by four techniques: Orbscan IIz(r) (Bausch and Lomb),
Lenstar LS 900(r) (Haag-Streit), Cassini(r) (i-Optics), and Total Cassini
(anterior + posterior surface), in healthy volunteers. Patients and methods:
Fifteen healthy volunteers (30 eyes) were assessed by the four techniques. In
each eye, three consecutive measures were performed by the same operator.
Keratometric and astigmatism values were recorded. The intraclass correlation
coefficient (ICC) was used to assess comparability and repeatability. Agreement
between measurement techniques was evaluated with Bland-Altman plots. Results:
Comparability was high between all measurement techniques for minimum keratometry
(K1), maximum keratometry (K2), astigmatism magnitude, and astigmatism axis, with
ICC >0.900, except for astigmatism magnitude measured by Cassini compared to
Lenstar (ICC =0.798) and Orbscan compared to Lenstar (ICC =0.810). However, there
were some differences in the median values of K1 and K2 between measurement
techniques, and the Bland-Altman plots showed a wide data spread for all
variables, except for astigmatism magnitude measured by Cassini and Total
Cassini. For J0 and J45, comparability was only high for J0 between Cassini and
Orbscan. Repeatability was also high for all measurement techniques except for K2
(ICC =0.814) and J45 (ICC =0.621) measured by Cassini. Conclusion: All
measurement techniques showed high comparability regarding K1, K2, and
astigmatism axis. Although posterior corneal surface is known to influence these
measurements, comparability was high between Cassini and Total Cassini regarding
astigmatism magnitude and axis. However, the wide data spread suggests that none
of these devices should be used interchangeably.
PMID- 29339919
TI - Effect of oral tranexamic acid on macular edema associated with retinal vein
occlusion or diabetes.
AB - Purpose: Tranexamic acid (TXA) is a widely used antifibrinolytic agent that can
also cause a decrease in vascular permeability. We hypothesized that TXA could
improve macular edema (ME) that is caused by an increase in retinal vascular
permeability. The aim of this study is to evaluate the efficacy of oral TXA for
ME associated with retinal vein occlusion (RVO) or diabetic ME (DME). Patients
and methods: Oral TXA (1,500 mg daily for 2 weeks) was administered to patients
with persistent ME secondary to RVO (7 eyes) and DME (7 eyes). After 2 weeks (ie,
the final day of administration) and 6 weeks (ie, 4 weeks after the final
administration), best-corrected visual acuity and central macular thickness (CMT)
were measured and compared with baseline. Analyses were performed for RVO and DME
cases. No other treatment was performed during the study period. Results: In RVO
cases, significant improvement in CMT was found between baseline (467.7+/-121.4
MUm) and 2-week measurements after treatment (428.7+/-110.5 MUm, p=0.024). No
significant change was found in CMT between measurements taken at baseline and 6
weeks after treatment. In DME cases, no significant change was found in CMT
between measurements taken at baseline and 2 or 6 weeks after treatment. In all
analyses of best-corrected visual acuity, no significant change was observed.
Conclusion: The results support the hypothesis that plasmin plays a role in the
development of ME associated with RVO, and oral TXA administration may be useful
as an adjuvant treatment when combined with other agents such as anti-vascular
endothelial growth factor.
PMID- 29339920
TI - Microhook ab interno trabeculotomy, a novel minimally invasive glaucoma surgery.
AB - Trabeculotomy (LOT) is performed to reduce the intraocular pressure in patients
with glaucoma, both in children and adults. It relieves the resistance to aqueous
flow by cleaving the trabecular meshwork and the inner walls of Schlemm's canal.
Microhook ab interno LOT (uLOT), a novel minimally invasive glaucoma surgery,
incises trabecular meshwork using small hooks that are inserted through corneal
side ports. An initial case series reported that both uLOT alone and combination
of uLOT and cataract surgery normalize the intraocular pressure during the early
postoperative period in Japanese patients with glaucoma. Microhook can incise the
inner wall of Schlemm's canal without damaging its outer wall easier than the
regular straight knife that is used during goniotomy. Advantages of uLOT include:
a wider extent of LOT (two-thirds of the circumference), a simpler surgical
technique, being less invasiveness to the ocular surface, a shorter surgical time
than traditional ab externo LOT, and no requirement for expensive devices. In
this paper, the surgical technique of uLOT and tips of the technique are
introduced.
PMID- 29339921
TI - Cardiopulmonary exercise test and PaO2 in evaluation of pulmonary hypertension in
COPD.
AB - Background: Exercise tolerance decreases as COPD progresses. Pulmonary
hypertension (PH) is common in COPD and may reduce performance further. COPD
patients with and without PH could potentially be identified by cardiopulmonary
exercise test (CPET). However, results from previous studies are diverging, and a
unified conclusion is missing. We hypothesized that CPET combined with arterial
blood gases is useful to discriminate between COPD outpatients with and without
PH. Methods: In total, 93 COPD patients were prospectively included. Pulmonary
function tests, right heart catheterization, and CPET with blood gases were
performed. The patients were divided, by mean pulmonary artery pressure, into
COPD-noPH (<25 mmHg) and COPD-PH (>=25 mmHg) groups. Linear mixed models (LMMs)
were fitted to estimate differences when repeated measurements during the course
of exercise were considered and adjusted for gender, age, and airway obstruction.
Results: Ventilatory and/or hypoxemic limitation was the dominant cause of
exercise termination. In LMM analyses, significant differences between COPD-noPH
and COPD-PH were observed for PaO2, SaO2, PaCO2, ventilation, respiratory
frequency, and heart rate. PaO2 <61 mmHg (8.1 kPa) during unloaded pedaling, the
only load level achieved by all the patients, predicted PH with a sensitivity of
86% and a specificity of 78%. Conclusion: During CPET, low exercise performance
and PaO2 strongly indicated PH in COPD patients.
PMID- 29339922
TI - Effect of rhythmic auditory cueing on gait in cerebral palsy: a systematic review
and meta-analysis.
AB - Auditory entrainment can influence gait performance in movement disorders. The
entrainment can incite neurophysiological and musculoskeletal changes to enhance
motor execution. However, a consensus as to its effects based on gait in people
with cerebral palsy is still warranted. A systematic review and meta-analysis
were carried out to analyze the effects of rhythmic auditory cueing on
spatiotemporal and kinematic parameters of gait in people with cerebral palsy.
Systematic identification of published literature was performed adhering to
Preferred Reporting Items for Systematic Reviews and Meta-Analyses and American
Academy for Cerebral Palsy and Developmental Medicine guidelines, from inception
until July 2017, on online databases: Web of Science, PEDro, EBSCO, Medline,
Cochrane, Embase and ProQuest. Kinematic and spatiotemporal gait parameters were
evaluated in a meta-analysis across studies. Of 547 records, nine studies
involving 227 participants (108 children/119 adults) met our inclusion criteria.
The qualitative review suggested beneficial effects of rhythmic auditory cueing
on gait performance among all included studies. The meta-analysis revealed
beneficial effects of rhythmic auditory cueing on gait dynamic index (Hedge's
g=0.9), gait velocity (1.1), cadence (0.3), and stride length (0.5). This review
for the first time suggests a converging evidence toward application of rhythmic
auditory cueing to enhance gait performance and stability in people with cerebral
palsy. This article details underlying neurophysiological mechanisms and use of
cueing as an efficient home-based intervention. It bridges gaps in the
literature, and suggests translational approaches on how rhythmic auditory cueing
can be incorporated in rehabilitation approaches to enhance gait performance in
people with cerebral palsy.
PMID- 29339923
TI - An acute bout of housework activities has beneficial effects on executive
function.
AB - Purpose: Although acute bouts of exercise reportedly have beneficial effects on
executive function, inactive people may find it difficult to start exercising. In
this study, we focused on housework activities (HAs) that generate a sense of
accomplishment and require a mild intensity of physical activity. We examined the
impact of an acute bout of HA on executive function and oxygenated hemoglobin
(oxy-Hb) flow to related cortical regions. Materials and methods: Twenty-five
participants (age, 18-21 years; mean, 19.88+/-0.60 years; six males and 19
females) underwent two experiments, ie, HA and control experiments, which were
conducted on different days. Participants vacuumed a dirty floor in the HA
experiment and mimicked the same motion with an unplugged vacuum cleaner on a
clean floor in the control experiment. Results: Heart rate recorded during the
experiments showed no significant difference in the intensity of physical
activity between control and HA groups. A questionnaire revealed a sense of
accomplishment after completing the HA experiment. Participants performed the
Stroop color-word task (SCWT) pre- and post-experiments; cortical hemodynamic
changes were simultaneously monitored using functional near-infrared
spectroscopy. Variation in Stroop interference scores for SCWT total response
between pre- and post-experiments was signifi-cantly higher in the HA group than
in the control group, and that for SCWT correct response showed a similar trend.
Variation in the Stroop interference score for oxy-Hb flow to the right
ventrolateral prefrontal cortex (R-VLPFC) showed the same trend. Conclusion:
Thus, HAs may have a greater beneficial effect on executive function than other
physical activities through the activation of PFC, including R-VLPFC.
PMID- 29339924
TI - Quality of life and coping strategies of outpatients with a depressive disorder
in maintenance therapy - a cross-sectional study.
AB - Background: The quality of life (QoL) is a multidimensional view that represents
all aspects of patient well-being in various areas of patient life. Specific
coping strategies may be connected to both the QoL and the severity of mental
disorder. The aim of this investigation was to examine the relationship between
the QoL and the coping strategies of outpatients with a depressive disorder.
Methods: Eighty-two outpatients, who met the criteria of the International
Classification of Diseases, Tenth Revision, for a depressive disorder, were
enrolled in the cross-sectional study. Data on sociodemographic and clinical
variables were obtained from the medical records. Individuals filled the
following standardized questionnaires: Quality of Life Satisfaction and Enjoyment
Questionnaire, Stress Coping Style Questionnaire, and Clinical Global Impression.
Multiple regression analyses with backward elimination were performed to discover
the most influential factors contributing to QoL. Results: The participants with
a depressive disorder showed an overuse of negative coping strategies, especially
escape tendency and resignation. A positive self-instruction strategy was used by
the patients less often. The coping strategies were significantly associated with
the QoL. A more frequent use of positive coping strategies had a positive
association with the QoL. The main factors related to QoL were the subjective
severity of the disorder, employment, and positive coping strategies. Conclusion:
The study confirmed the relationship between QoL and the coping strategies of
outpatients with a depressive disorder.
PMID- 29339925
TI - miR-136 targets MIEN1 and involves the metastasis of colon cancer by suppressing
epithelial-to-mesenchymal transition.
AB - MIEN1 is a novel oncogene, and it involves tumor progression in various cancer
types, including colon cancer. However, the definite molecular mechanisms of
MIEN1 in colon cancer progression remain to be completely elucidated. In the
present study, bioinformatics prediction showed that miR-136 could be an upstream
regulator of MIEN1; a luciferase assay and Western blot assay revealed that miR
136 negatively regulates MIEN1 expression via directly targeting its 3'
untranslated region sequence. Moreover, a functional assay using wound healing
and transwell invasion showed that overexpressed miR-136 inhibited cell migration
and invasion, and overexpression of MIEN1 partly rescued the above-mentioned
effects of miR-136 in colon cancer cells. Additionally, a clinical sample assay
showed that miR-136 expression was generally downregulated in colon cancer
tissue, which was inversely correlated with MIEN1 expression. Furthermore, we
found that miR-136 suppressed the Akt/NF-kappaB signaling pathway and epithelial
to-mesenchymal transition in colon cancer. These results suggest that miR-136, as
a tumor suppressor, acts in tumor metastasis by suppressing MIEN1 expression in
colon cancer, providing a novel target for the treatment of colon cancer.
PMID- 29339926
TI - Using a chronic hepatitis B Registry to support population-level liver cancer
prevention in Sydney, Australia.
AB - Background: Approximately 1% of Australians have chronic hepatitis B (CHB), which
disproportionately affects people born in hepatitis B-endemic countries.
Currently, approximately half of the people affected remain undiagnosed and
antiviral treatment uptake is suboptimal (~5%). This increases the likelihood of
developing end-stage disease complications, particularly hepatocellular cancer
(HCC), and largely accounts for the significant increases in HCC incidence and
mortality in Australia over the last decades. As our previous economic modeling
suggested that CHB screening and treatment is cost-effective, we tested the
feasibility of a primary care-based model of CHB diagnosis and management to
prevent HCC. Materials and methods: From 2009 to 2016, the B Positive program
trialed a CHB screening and management program in an area of high disease
prevalence in Sydney, Australia. Trained local primary care providers (general
practitioners) screened and managed their CHB patients using a purpose-built CHB
Registry and a risk stratification algorithm, which allocated patients to ongoing
primary care-based management or specialist referral. Results: The program
enrolled and followed up >1,500 people (25% of the target population). Their
median age was 48 years, with most participants being born in China (50%) or
Vietnam (32%). The risk stratification algorithm allocated most Registry
participants (n=847 or 79%) to primary care-based management, reducing
unnecessary specialist referrals. The level of antiviral treatment uptake in
Registry patients was 18%, which was the optimal level in this population group.
Conclusion: This pilot program demonstrated that primary care-based hepatitis B
diagnosis and management is acceptable to patients and their care providers and
significantly increases compliance with treatment guidelines. This would suggest
that scaling up access to hepatitis B treatment is achievable and can provide a
means to operationalize a population-level approach to CHB management and liver
cancer prevention.
PMID- 29339927
TI - Factors affecting the cultural competence of visiting nurses for rural
multicultural family support in South Korea.
AB - Background: With the recent growth of multicultural families in the Korean
society, the importance of the role of qualified visiting nurses in the delivery
of culturally sensitive health care has grown dramatically. As the primary health
care provider for multicultural families enrolled in public community-based
health care centers, the cultural competence of visiting nurses is an essential
qualification for the provision of quality health care for multicultural
families, especially in rural areas. Cultural competence of visiting nurses is
based on their cultural awareness and empathetic attitude toward multicultural
families. This study aimed to examine the levels of cultural competence,
empowerment, and empathy in visiting nurses, and to verify the factors that
affect the cultural competence of visiting nurses working with rural
multicultural families in South Korea. Methods: Employing a cross-sectional
descriptive study design, data from 143 visiting nurses working in rural areas
were obtained. Data collection took place between November 2011 and August 2012.
The measurement tools included the modified Korean version of the Cultural
Awareness Scale, the Text of Items Measuring Empowerment, and the Interpersonal
Reactivity Index to measure the level of empathy of visiting nurses. Analyses
included descriptive statistics, a t-test, an ANOVA, a Pearson correlation
coefficient analysis, and a multiple linear regression analysis. Results: The
cultural competence score of the visiting nurses was 3.07 on a 5-point Likert
scale (SD = 0.30). The multiple regression analysis revealed that the cultural
competence of visiting nurses was significantly influenced by experience of
cultural education, empathy, and scores on the meaning subscale of the
empowerment tool (R2 = 10.2%). Conclusions: Institutional support to enhance
visiting nurses' empowerment by assuring the significance of their job and
specific strategies to enhance their empathy would be helpful to improve the
cultural competence of visiting nurses. Additionally, regular systematic
education on culturally sensitive care would be helpful to enable visiting nurses
to provide culturally sensitive care for multicultural families.
PMID- 29339928
TI - Chemical proteomics, an integrated research engine for exploring drug-target
phenotype interactions.
PMID- 29339930
TI - Research evaluation support services in biomedical libraries.
AB - Objective: The paper provides a review of current practices related to evaluation
support services reported by seven biomedical and research libraries. Methods: A
group of seven libraries from the United States and Canada described their
experiences with establishing evaluation support services at their libraries. A
questionnaire was distributed among the libraries to elicit information as to
program development, service and staffing models, campus partnerships, training,
products such as tools and reports, and resources used for evaluation support
services. The libraries also reported interesting projects, lessons learned, and
future plans. Results: The seven libraries profiled in this paper report a
variety of service models in providing evaluation support services to meet the
needs of campus stakeholders. The service models range from research center
cores, partnerships with research groups, and library programs with staff
dedicated to evaluation support services. A variety of products and services were
described such as an automated tool to develop rank-based metrics, consultation
on appropriate metrics to use for evaluation, customized publication and citation
reports, resource guides, classes and training, and others. Implementing these
services has allowed the libraries to expand their roles on campus and to
contribute more directly to the research missions of their institutions.
Conclusions: Libraries can leverage a variety of evaluation support services as
an opportunity to successfully meet an array of challenges confronting the
biomedical research community, including robust efforts to report and demonstrate
tangible and meaningful outcomes of biomedical research and clinical care. These
services represent a transformative direction that can be emulated by other
biomedical and research libraries.
PMID- 29339929
TI - Inositol depletion, GSK3 inhibition and bipolar disorder.
AB - Valproic acid and lithium are widely used to treat bipolar disorder, a severe
illness characterized by cycles of mania and depression. However, their efficacy
is limited, and treatment is often accompanied by serious side effects. The
therapeutic mechanisms of these drugs are not understood, hampering the
development of more effective treatments. Among the plethora of biochemical
effects of the drugs, those that are common to both may be more related to
therapeutic efficacy. Two common outcomes include inositol depletion and GSK3
inhibition, which have been proposed to explain the efficacy of both valproic
acid and lithium. Here, we discuss the inositol depletion and GSK3 inhibition
hypotheses, and introduce a unified model suggesting that inositol depletion and
GSK3 inhibition are inter-related.
PMID- 29339931
TI - Assessment of knowledge and skills in information literacy instruction for
rehabilitation sciences students: a scoping review.
AB - Objective: This scoping review investigates how knowledge and skills are assessed
in the information literacy (IL) instruction for students in physical therapy,
occupational therapy, or speech-language pathology, regardless of whether the
instruction was given by a librarian. The objectives were to discover what
assessment measures were used, determine whether these assessment methods were
tested for reliability and validity, and provide librarians with guidance on
assessment methods to use in their instruction in evidence-based practice
contexts. Methods: A scoping review methodology was used. A systematic search
strategy was run in Ovid MEDLINE and adapted for CINAHL; EMBASE; Education
Resources Information Center (ERIC) (EBSCO); Library and Information Science
Abstracts (LISA); Library, Information Science & Technology Abstracts (LISTA);
and Proquest Theses and Dissertations from 1990 to January 16, 2017. Forty
articles were included for data extraction. Results: Three major themes emerged:
types of measures used, type and context of librarian involvement, and skills and
outcomes described. Thirty-four measures of attitude and thirty-seven measures of
performance were identified. Course products were the most commonly used type of
performance measure. Librarians were involved in almost half the studies, most
frequently as instructor, but also as author or assessor. Information literacy
skills such as question formulation and database searching were described in
studies that did not involve a librarian. Conclusion: Librarians involved in
instructional assessment can use rubrics such as the Valid Assessment of Learning
in Undergraduate Education (VALUE) when grading assignments to improve the
measurement of knowledge and skills in course-integrated IL instruction. The
Adapted Fresno Test could be modified to better suit the real-life application of
IL knowledge and skills.
PMID- 29339932
TI - Computerized versus hand-scored health literacy tools: a comparison of Simple
Measure of Gobbledygook (SMOG) and Flesch-Kincaid in printed patient education
materials.
AB - Objective: The research compared and contrasted hand-scoring and computerized
methods of evaluating the grade level of patient education materials that are
distributed at an academic medical center in east Tennessee and sought to
determine if these materials adhered to the American Medical Association's
(AMA's) recommended reading level of sixth grade. Methods: Librarians at an
academic medical center located in the heart of Appalachian Tennessee initiated
the assessment of 150 of the most used printed patient education materials. Based
on the Flesch-Kincaid (F-K) scoring rubric, 2 of the 150 documents were excluded
from statistical comparisons due to the absence of text (images only).
Researchers assessed the remaining 148 documents using the hand-scored Simple
Measure of Gobbledygook (SMOG) method and the computerized F-K grade level
method. For SMOG, 3 independent reviewers hand-scored each of the 150 documents.
For F-K, documents were analyzed using Microsoft Word. Reading grade levels
scores were entered into a database for statistical analysis. Inter-rater
reliability was calculated using intra-class correlation coefficients (ICC).
Paired t-tests were used to compare readability means. Results: Acceptable inter
rater reliability was found for SMOG (ICC=0.95). For the 148 documents assessed,
SMOG produced a significantly higher mean reading grade level (M=9.6, SD=1.3)
than F-K (M=6.5, SD=1.3; p<0.001). Additionally, when using the SMOG method of
assessment, 147 of the 148 documents (99.3%) scored above the AMA's recommended
reading level of sixth grade. Conclusions: Computerized health literacy
assessment tools, used by many national patient education material providers,
might not be representative of the actual reading grade levels of patient
education materials. This is problematic in regions like Appalachia because
materials may not be comprehensible to the area's low-literacy patients. Medical
librarians have the potential to advance their role in patient education to
better serve their patient populations.
PMID- 29339933
TI - Roles for librarians in systematic reviews: a scoping review.
AB - Objective: What roles do librarians and information professionals play in
conducting systematic reviews? Librarians are increasingly called upon to be
involved in systematic reviews, but no study has considered all the roles
librarians can perform. This inventory of existing and emerging roles aids in
defining librarians' systematic reviews services. Methods: For this scoping
review, the authors conducted controlled vocabulary and text-word searches in the
PubMed; Library, Information Science & Technology Abstracts; and CINAHL
databases. We separately searched for articles published in the Journal of the
European Association for Health Information and Libraries, Evidence Based Library
and Information Practice, the Journal of the Canadian Heath Libraries
Association, and Hypothesis. We also text-word searched Medical Library
Association annual meeting poster and paper abstracts. Results: We identified 18
different roles filled by librarians and other information professionals in
conducting systematic reviews from 310 different articles, book chapters, and
presented papers and posters. Some roles were well known such as searching,
source selection, and teaching. Other less documented roles included planning,
question formulation, and peer review. We summarize these different roles and
provide an accompanying bibliography of references for in-depth descriptions of
these roles. Conclusion: Librarians play central roles in systematic review
teams, including roles that go beyond searching. This scoping review should
encourage librarians who are fulfilling roles that are not captured here to
document their roles in journal articles and poster and paper presentations.
PMID- 29339934
TI - Publication outcome of abstracts submitted to the American Academy of
Ophthalmology meeting.
AB - Objective: Abstracts submitted to meetings are subject to less rigorous peer
review than full-text manuscripts. This study aimed to explore the publication
outcome of abstracts presented at the American Academy of Ophthalmology (AAO)
annual meeting. Methods: Abstracts presented at the 2008 AAO meeting were
analyzed. Each presented abstract was sought via PubMed to identify if it had
been published as a full-text manuscript. The publication outcome, journal impact
factor (IF), and time to publication were recorded. Results: A total of 690
abstracts were reviewed, of which 39.1% were subsequently published. They were
published in journals with a median IF of 2.9 (range 0-7.2) and a median
publication time of 426 days (range 0-2,133 days). A quarter were published in
the journal Ophthalmology, with a shorter time to publication (median 282 vs. 534
days, p=0.003). Oral presentations were more likely to be published than poster
presentations (57.8% vs. 35.9%, p<0.001) and in journals with higher IFs (3.2 vs.
2.8, p=0.02). Abstracts describing rare diseases had higher publication rates
(49.4% vs. 38.0%, p=0.04) and were published in higher IF journals (3.7 vs. 2.9,
p=0.03), within a shorter period of time (358 vs. 428 days, p=0.03). In
multivariate analysis, affiliation with an institute located in the United States
(p=0.002), abstracts describing rare diseases (p=0.03), and funded studies
(p=0.03) were associated with publication in higher IF journals. Conclusions:
Almost 40% of abstracts were published. Factors that correlated with publication
in journals with higher IF were a focus on rare diseases, affiliation with a US
institute, and funding.
PMID- 29339935
TI - Dietetic interns' perceptions and use of evidence-based practice: an exploratory
study.
AB - Objective: This study explored dietetic interns' perceptions and knowledge of
evidence-based practice (EBP), their use and observation of EBP principles during
their clinical rotations, and their intentions to use EBP in their careers.
Methods: A mixed methods design combining a survey and focus group was employed.
Dietetic interns (n=16) from a large Midwestern university were recruited in
person and via email to participate in the survey, focus group, or both.
Perceptions and experiences of EBP were analyzed through the focus group
(qualitative), and EBP knowledge and clinical practice behaviors were analyzed
through the survey (quantitative). The focus group discussion was recorded,
transcribed, and analyzed using thematic analysis. Results: Four major themes
emerged from the focus group data: (1) observations of EBP in clinical practice,
(2) use of EBP during clinical rotations, (3) barriers to EBP, and (4) perceived
use of EBP as future registered dietitians. Interns considered EBP important for
their profession and future careers. They struggled, however, with the
discrepancies between current research and practice, and highlighted differences
that they observed and barriers that they experienced across different clinical
settings. Conclusions: This exploratory study is the first to examine dietetic
interns' perceptions of and experiences with EBP in the clinical setting. Future
research is needed to identify how dietetics educators, librarians, and
preceptors can address the barriers that interns perceive in applying EBP in
their internships.
PMID- 29339936
TI - Satellite stories: capturing professional experiences of academic health sciences
librarians working in delocalized health sciences programs.
AB - Objective: Health sciences training programs have progressively expanded onto
satellite campuses, allowing students the opportunity to learn in communities
away from an academic institution's main campus. This expansion has encouraged a
new role for librarians to assume, in that a subset of health sciences librarians
identify as "satellite librarians" who are permanently located at a distance from
the main campus. Due to the unique nature of this role and lack of existing data
on the topic, the authors investigated the experiences and perceptions of this
unique group of information professionals. Methods: An electronic survey was
distributed to health sciences librarians via two prominent North American email
discussion lists. Questions addressed the librarians' demographics, feelings of
social inclusion, technological support, autonomy, professional support, and
more. Results: Eighteen surveys were analyzed. While several respondents stated
that they had positive working relationships with colleagues, many cited issues
with technology, scheduling, and lack of consideration as barriers to feeling
socially included at both the parent and local campuses. Social inclusion, policy
creation, and collection management issues were subject to their unique
situations and their colleagues' perceptions of their roles as satellite
librarians. Conclusions: The results from this survey suggest that the role of
the academic health sciences librarian at the satellite campus needs to be
clearly communicated and defined. This, in turn, will enhance the experience for
the librarian and provide better service to the client.
PMID- 29339937
TI - Discrepancies among Scopus, Web of Science, and PubMed coverage of funding
information in medical journal articles.
AB - Objective: The overall aim of the present study was to compare the coverage of
existing research funding information for articles indexed in Scopus, Web of
Science, and PubMed databases. Methods: The numbers of articles with funding
information published in 2015 were identified in the three selected databases and
compared using bibliometric analysis of a sample of twenty-eight prestigious
medical journals. Results: Frequency analysis of the number of articles with
funding information showed statistically significant differences between Scopus,
Web of Science, and PubMed databases. The largest proportion of articles with
funding information was found in Web of Science (29.0%), followed by PubMed
(14.6%) and Scopus (7.7%). Conclusion: The results show that coverage of funding
information differs significantly among Scopus, Web of Science, and PubMed
databases in a sample of the same medical journals. Moreover, we found that,
currently, funding data in PubMed is more difficult to obtain and analyze
compared with that in the other two databases.
PMID- 29339938
TI - Understanding cancer survivors' information needs and information-seeking
behaviors for complementary and alternative medicine from short- to long-term
survival: a mixed-methods study.
AB - Objective: The research examined complementary and alternative medicine (CAM)
information-seeking behaviors and preferences from short- to long-term cancer
survival, including goals, motivations, and information sources. Methods: A mixed
methods approach was used with cancer survivors from the "Assessment of Patients'
Experience with Cancer Care" 2004 cohort. Data collection included a mail survey
and phone interviews using the critical incident technique (CIT). Results:
Seventy survivors from the 2004 study responded to the survey, and eight
participated in the CIT interviews. Quantitative results showed that CAM usage
did not change significantly between 2004 and 2015. The following themes emerged
from the CIT: families' and friends' provision of the initial introduction to a
CAM, use of CAM to manage the emotional and psychological impact of cancer,
utilization of trained CAM practitioners, and online resources as a prominent
source for CAM information. The majority of participants expressed an interest in
an online information-sharing portal for CAM. Conclusion: Patients continue to
use CAM well into long-term cancer survivorship. Finding trustworthy sources for
information on CAM presents many challenges such as reliability of source,
conflicting information on efficacy, and unknown interactions with conventional
medications. Study participants expressed interest in an online portal to meet
these needs through patient testimonials and linkage of claims to the scientific
literature. Such a portal could also aid medical librarians and clinicians in
locating and evaluating CAM information on behalf of patients.
PMID- 29339939
TI - Library instruction in medical education: a survey of current practices in the
United States and Canada.
AB - Objective: The most recent survey on instruction practices in libraries
affiliated with accredited medical institutions in the United States was
conducted in 1996. The present study sought to update these data, while expanding
to include Canadian libraries. Additional analysis was undertaken to test for
statistically significant differences between library instruction in the United
States and Canada and between libraries affiliated with highly ranked and
unranked institutions. Methods: A twenty-eight-question survey was distributed to
libraries affiliated with accredited US and Canadian medical schools to assess
what and how often librarians teach, as well as how librarians are involved in
the curriculum committee and if they are satisfied with their contact with
students and faculty. Quantitative data were analyzed with SAS, R, and MedCalc.
Results: Most of the seventy-three responding libraries provided instruction,
both asynchronously and synchronously. Library instruction was most likely to be
offered in two years of medical school, with year one seeing the most activity.
Database use was the most frequently taught topic, and libraries reported a
median of five librarians providing instruction, with larger staffs offering
slightly more education sessions per year. Libraries associated with highly
ranked schools were slightly more likely to offer sessions that were integrated
into the medical school curriculum in year four and to offer sessions in more
years overall. Conclusions: In US and Canadian libraries, regardless of the rank
of the affiliated medical school, librarians' provision of instruction in
multiple formats on multiple topics is increasingly common.
PMID- 29339940
TI - Applying an information literacy rubric to first-year health sciences student
research posters.
AB - Objective: This article describes the collection and analysis of annotated
bibliographies created by first-year health sciences students to support their
final poster projects. The authors examined the students' abilities to select
relevant and authoritative sources, summarize the content of those sources, and
correctly cite those sources. Methods: We collected images of 1,253 posters, of
which 120 were sampled for analysis, and scored the posters using a 4-point
rubric to evaluate the students' information literacy skills. Results: We found
that 52% of students were proficient at selecting relevant sources that directly
contributed to the themes, topics, or debates presented in their final poster
projects, and 64% of students did well with selecting authoritative peer-reviewed
scholarly sources related to their topics. However, 45% of students showed
difficulty in correctly applying American Psychological Association (APA)
citation style. Conclusion: Our findings demonstrate a need for instructors and
librarians to provide strategies for reading and comprehending scholarly articles
in addition to properly using APA citation style.
PMID- 29339941
TI - Building capacity to encourage research reproducibility and #MakeResearchTrue.
AB - Background: Research into study replication and reporting has led to wide concern
about a reproducibility crisis. Reproducibility is coming to the attention of
major grant funders, including the National Institutes of Health, which launched
new grant application instructions regarding rigor and reproducibility in 2015.
Study Purpose: In this case study, the authors present one library's work to help
increase awareness of reproducibility and to build capacity for our institution
to improve reproducibility of ongoing and future research. Case Presentation:
Library faculty partnered with campus research leaders to create a daylong
conference on research reproducibility, followed by a post-conference day with
workshops and an additional seminar. Attendees came from nearly all schools and
colleges on campus, as well as from other institutions, nationally and
internationally. Feedback on the conference was positive, leading to efforts to
sustain the momentum achieved at the conference. New networking and educational
opportunities are in development. Discussion: Libraries are uniquely positioned
to lead educational and capacity-building efforts on campus around research
reproducibility. Costs are high and partnerships are required, but such efforts
can lead to positive change institution-wide.
PMID- 29339942
TI - A new hat for librarians: providing REDCap support to establish the library as a
central data hub.
AB - Background: REDCap, an electronic data capture tool, supports good research data
management, but many researchers lack familiarity with the tool. While a REDCap
administrator provided technical support and a clinical data management support
unit provided study design support, a service gap existed. Case Presentation:
Librarians with REDCap expertise sought to increase and improve usage through
outreach, workshops, and consultations. In collaboration with a REDCap
administrator and the director of the clinical data management support unit, the
role of the library was established in providing REDCap training and
consultations. REDCap trainings were offered to the medical center during the
library's quarterly data series, which served as a springboard for offering
tailored REDCap support to researchers and research groups. Conclusions:
Providing REDCap support has proved to be an effective way to associate the
library with data-related activities in an academic medical center and identify
new opportunities for offering data services in the library. By offering REDCap
services, the library established strong partnerships with the Information
Technology Department, Clinical Data Support Department, and Compliance Office by
filling in training gaps, while simultaneously referring users back to these
departments when additional expertise was required. These new partnerships
continue to grow and serve to position the library as a central data hub in the
institution.
PMID- 29339943
TI - The case for consistent use of medical eponyms by eliminating possessive forms.
PMID- 29339944
TI - Building a body of knowledge: sickle cell and libraries.
PMID- 29339946
TI - Functional Heartburn.
PMID- 29339945
TI - Correction.
AB - [This corrects the article on p. 240 in vol. 105, PMID: 28670211.].
PMID- 29339947
TI - Vaccination and Health Maintenance Issues to Consider in Patients With
Inflammatory Bowel Disease.
AB - Patients with inflammatory bowel disease (IBD) do not receive routine preventive
care at the same rate as the general population. IBD places patients at increased
risk for developing vaccine-preventable illnesses. This risk is further
exacerbated by immunosuppressive therapy. This article highlights the necessary
vaccinations for IBD patients and the timing of vaccination for immunosuppressed
patients, and discusses the health maintenance needs and preventive care issues
related to heart disease, smoking, osteoporosis, mental health, cervical cancer,
and skin cancer.
PMID- 29339949
TI - Intragastric Balloons for Obesity Management.
PMID- 29339948
TI - Update on Functional Heartburn.
AB - The definition of functional heartburn has been refined over the years. It is
currently described, based upon Rome IV criteria, as typical heartburn symptoms
in the presence of normal upper endoscopy findings (including normal biopsies),
normal esophageal pH testing, and a negative association between symptoms and
reflux events. Functional heartburn is very common, affecting women more than
men, and with reflux hypersensitivity makes up the majority of heartburn patients
who fail twice-daily proton pump inhibitor therapy. These disorders overlap with
other functional gastrointestinal disorders and are often accompanied by
psychological comorbidities. Diagnosis is made by using endoscopy with esophageal
biopsies, wireless pH capsule, pH-impedance monitoring, and high-resolution
esophageal manometry. Additional diagnostic tools that may be of value include
magnification endoscopy, chromoendoscopy, narrow-band imaging, autofluorescence
imaging, mucosal impedance, impedance baseline values, and histopathology scores.
Functional heartburn is primarily treated with neuromodulators. Psychological
intervention and complementary and alternative medicine may also play important
roles in the treatment of these patients.
PMID- 29339950
TI - Beta-Catenin Staining of Hepatocellular Adenomas.
PMID- 29339951
TI - Benefits, Concerns, and Future Directions of Biosimilars in Inflammatory Bowel
Disease.
PMID- 29339952
TI - Narrow-Band Imaging for Diagnosing Gastroesophageal Reflux Disease.
PMID- 29339954
TI - Highlights in Clostridium difficile Infection From the World Congress of
Gastroenterology at ACG 2017: October 13-18, 2017 * Orlando, Florida.
PMID- 29339953
TI - Overview of the Updated AASLD Guidelines for the Management of HCC.
PMID- 29339955
TI - Highlights in Functional Dyspepsia Treatment From Digestive Disease Week 2017:
May 6-9, 2017 * Chicago, Illinois.
PMID- 29339956
TI - CSACI position statement: prescribing sublingual immunotherapy tablets for
aeroallergens.
PMID- 29339957
TI - A Case of Synchronised Pupillary and Nasal Cycling: Evidence for a Central
Autonomic Pendulum?
AB - We previously reported that some healthy individuals show alternating anisocoria.
We now describe one such individual who also exhibits a classic nasal cycle
(alternating periods of nasal congestion and decongestion). We made measurements
of his pupil asymmetry and nasal asymmetry at 21 different time points and found
that these variables were always synchronised such that greater nasal airflow was
invariably found on the same side as the larger pupil. We hypothesise that a
common central oscillator may be responsible for co-modulating the sympathetic
outflow to both nasal vessels and iris dilator muscles in some healthy
individuals.
PMID- 29339959
TI - Medical Cannabis, a Beneficial High in Treatment of Blepharospasm? An Early
Observation.
AB - The objective of this study was to observe the effect of medical cannabis in
benign essential blepharospasm (BEB) as an adjunct to botulinum toxin. A
retrospective chart review was performed on patients certified for medical
cannabis use for BEB from September 2015 to May 2016. Patient demographics and
responses, cannabis history, and severity indices were collected. Ten patients
were certified for medical cannabis use. Five met the inclusion criteria, which
was any patient with a diagnosis of BEB receiving standard botulinum toxin
treatment who had started medical cannabis treatment by a registered distributor
within the state, and was contactable by phone. Four patients discontinued use.
Three out of four patients (75%) reported symptomatic improvement. Medical
cannabis is an accepted therapy for muscle spastic disorders. Its potential as an
adjunctive therapy for BEB remains unknown, and further investigations would be
of benefit.
PMID- 29339958
TI - Validation of Simplified Visual Acuity Testing Protocols in Amyotrophic Lateral
Sclerosis.
AB - High- and low-contrast visual acuity (HCVA, LCVA) are potential quantitative
markers of neurological dysfunction in amyotrophic lateral sclerosis (ALS). The
complex nature and duration of gold standard (GS) protocols precludes widespread
use in neurology settings. This study compares simplified to GS visual acuity
(VA) protocols. Monocular HCVA and LCVA were measured in ALS (n = 10) and control
(n = 4) subjects using six protocols, varying by two chart and three refraction
methods. Intraclass correlation coefficients between simplified and GS protocols
ranged from 0.83 to 0.98 (HCVA, excellent agreement) and 0.56 to 0.75 (LCVA,
moderate agreement). Differences between LCVA and GS protocols exceeded test
retest reliability. Simplified HCVA protocols using LCD (liquid crystal display)
tablet charts and/or pinhole correction produced valid measurements. None of the
modified LCVA testing protocols produced valid measurements.
PMID- 29339960
TI - Which Differences in Priming Effect Between Neglect and Hemianopia? A Case
Description of a Bilateral Brain-Lesioned Patient.
AB - It is widely known that visuospatial neglect and hemianopia maybe superimposed.
We considered the differences in implicit information processing which is
effective in patients with neglect but not with hemianopia. We then hypothesize
that a prime-word in the neglected field should determine a semantic activation
effect but not in a blind hemifield. Moreover eye movements could provide further
details. In this work we considered a patient with a bilateral with the presence
of either a left visual neglect and a right homonymous hemianopia. Our results
supported implicit information processing in the space affected by neglect but
not by hemianopia.
PMID- 29339961
TI - Skew Deviation and Partial Ocular Tilt Reaction Due to Intratympanic Gentamicin
Injection, with Review of the Literature.
AB - Skew deviation is a rare side effect of intratympanic gentamicin injection for
intractable Meniere's disease. When the skew deviation is accompanied by
pathologic head tilt and ocular torsion, the result is an ocular tilt reaction
(OTR). The authors report the case of a 56-year-old man with refractory Meniere's
disease who developed binocular vertical diplopia following intratympanic
gentamicin injection and was found to have skew deviation and a partial ocular
tilt reaction. The authors also review the reported cases of skew deviation
following intratympanic gentamicin and confirm this phenomenon, which has only
rarely been reported in the literature.
PMID- 29339962
TI - Three New PAX2 Gene Mutations in Patients with Papillorenal Syndrome.
AB - Papillorenal syndrome (PAPRS; Mendelian Inheritance in Man [MIM] 120330) is an
autosomal dominant disease characterised by the presence of congenital renal and
optic nerve abnormalities associated with mutations of the PAX2 gene. In this
article, the authors present four patients with PAPRS who are carriers of three
new PAX2 mutations, as well as another patient with a possible non-pathogenic
variant of the PAX2 gene. All patients were given a full neurophthalmological
examination, and all patients underwent a genetic test for PAX2. Patients 1 and 2
presented with the classic signs of PAPRS: renal disease associated with a
congenitally abnormal optic disc, whereas patients 3 and 4 only presented with a
congenital optic nerve abnormality and no renal involvement. In patients 1 and 2,
the optic nerves were affected by the presence of a central excavation within the
optic disc, absence of the central retinal artery, as well as multiple
cilioretinal arteries radiating from the periphery of the optic disc. Bilateral
optic nerve pits were seen in patient 3, and lastly, in patient 4 there was the
presence of superficial gliotic tissue on the left optic disc. All patients
presented with a missense mutation in the PAX2 gene, where in patient 4 possibly
being only a non-pathogenic variant of the gene. In conclusion, the authors
present two patients with classic clinical signs of PAPRS, having two new PAX2
mutations, which until now have not been described in the current literature;
another patient with a new PAX2 mutation showing only ocular manifestations of
the disease, and lastly, a patient who is a carrier of a variant of the PAX2 gene
has a congenitally abnormal optic disc, which is probably not related to PAPRS.
PMID- 29339963
TI - Infiltrative Optic Neuropathies: Opening Doors to Sinister Pathologies.
AB - Optic disc edema may be caused by a number of conditions. A commonly ignored but
important aspect is the presence of "infiltration" of disc; that may closely
mimic disc edema. Disc edema, optic nerve dysfunction and a normal appearing disc
in any combination may occur in infiltrative optic neuropathies. Identifying disc
infiltration can aid in diagnosis of many sinister pathologies even in the
absence of other specific clinical features. We describe two patients presenting
with optic nerve dysfunction and infiltrated disc appearance, which on
investigations were found to have underlying malignancies thereby underscoring
the importance of detecting infiltrative optic neurpathies.
PMID- 29339964
TI - Cerebral Venous Thrombosis with Papilloedema Secondary to Skull Base
Plasmacytoma.
AB - A 60-year-old woman with history of multiple myeloma was in remission after stem
cell transplant 6 years prior. She was undergoing work-up for headaches that were
thought to be secondary to a right mastoiditis seen on magnetic resonance imaging
(MRI). On routine eye exam, papilloedema was noted. A lumbar puncture was
performed, with elevated opening pressure with normal constituents. She was an
atypical age for idiopathic intracranial hypertension, and her mastoiditis raised
concern for secondary cerebral venous sinus thrombosis. Magnetic resonance
venography (MRV) was performed showing poor flow in the right sigmoid sinus, and
computed tomography venography (CTV) showed lack of contrast enhancement distal
to the right sigmoid sinus, consistent with occlusion. There was also an
enhancing mass inferior to the right occipital bone. Biopsy confirmed recurrent
plasma cell myeloma. She was treated with chemotherapy, radiation, and warfarin
for presumed cerebral venous sinus thrombosis.
PMID- 29339965
TI - Bilateral Radiation Optic Neuropathy Following Concurrent Chemotherapy and
Radiation in Glioblastoma.
AB - Radiation optic neuropathy (RON) is an iatrogenic complication that causes
severe, irreversible vision loss within months to years following radiation to
lesions close to the visual pathway. The authors describe a case of RON in
glioblastoma after radio-sensitisation with temozolomide with sequential
involvement of both optic nerves. This case provides a timeline for clinical and
imaging findings with RON and specifically resolution of nerve enhancement. The
authors also highlight the potential of an increase in incidence of RON in
glioblastoma with advances in survival seen with greater use of second-line
chemotherapy and even re-radiation.
PMID- 29339966
TI - Acute diesel exhaust exposure and postural stability: a controlled crossover
experiment.
AB - Recent epidemiological evidence connects ambient air pollutants to adverse
neurobehavioural effects in adults. In animal models, subchronic controlled
exposures to diesel exhaust (DE) have also showed evidence of neuroinflammation.
Evidence suggests that DE not only affects outcomes commonly associated with
cognitive dysfunction, but also balance impairment. We conducted a controlled
human exposure experiment with 28 healthy subjects (average age = 28 years (SD =
7.1; range = 21-49); and 40% female) who were exposed to two conditions, filtered
air (FA) and DE (300 MUg PM2.5/m3) for 120 min, in a double-blinded crossover
study with randomized exposures separated by four weeks. Postural stability was
assessed by the Balance Error Scoring System (BESS), a brief, easily-administered
test of static balance. The BESS consists of a sequence of three stances
performed on two surfaces. With hands on hips and eyes closed, each stance is
held for 20 s. "Error" points are awarded for deviations from those stances. Pre-
and immediately post-exposure BESS "error" point totals were calculated and the
difference between the two timepoints were compared for each of the two exposure
conditions. A mixed effect model assessed the significance of the association.
While our data demonstrates a trend of reduced postural stability in response to
exposure to DE, exposure was not significantly associated with BESS value. This
is the first study to investigate changes in postural stability as a result of
exposure to DE in human subjects.
PMID- 29339967
TI - Preventing neonatal herpes infections through maternal immunization.
PMID- 29339968
TI - Analysis of questions about use of drugs in breastfeeding to Norwegian drug
information centres.
AB - Background: Health professionals may advise women to either stop breastfeeding or
drug treatment due to restrictive advice in drug monographs. Regional medicines
information and pharmacovigilance centres in Norway (RELIS) provide free and
industry-independent answers to questions about drugs and breastfeeding
documented in a full-text, searchable database (RELIS database). We used the
RELIS database to describe which health care practitioners sought information
about medication safety in lactation, most common drugs involved, advice provided
and which resources were used to provide the advice. Methods: A random selection
of 100 question-answer pairs (QAPs) from the RELIS database indexed with
"BREASTFEEDING" in the period from January 2011 to December 2015 was analysed.
Inclusion criteria were queries from health professionals about drugs. Questions
about herbal supplements and other exposures not classified as drugs were
excluded. The QAPs were manually analysed for compatibility of one or several
drugs with breastfeeding, health care profession and workplace of enquirer in
addition to advice and search strategy used. Results: In the 100 QAPs there were
enquires about 152 drugs. Seventy-four questions concerned a single drug, but the
number of drugs evaluated varied between 1 and 16. Fifty-nine questions were from
physicians, 34 from nurses or midwives, two from pharmacists and two from other
health professionals. Questions from physicians contained 93 drug evaluations
(61%), nurses or midwives 47 (31%) and pharmacists seven (5%). The most frequent
categories of drugs were antidepressants, antiepileptics and immunosuppressants.
The most asked about drugs were lamotrigine, codeine, quetiapine and
escitalopram. Fifty-nine percent of the drugs were deemed safe while
breastfeeding, 16% if precautions were taken and 12% not recommended. Thirty-nine
percent of the drug evaluations used an advanced literature search strategy, and
this was significantly (p < 0.05) more likely when the enquirer was a physician.
Conclusions: This analysis of questions to Norwegian medicines information
centres about medicine use in breastfeeding indicates the need for communication
about safety of drugs affecting the nervous system, primarily to medical doctors
and midwives. In the majority of cases the medicine information centre can
reassure about the safety of breastfeeding while taking a drug.
PMID- 29339969
TI - A new toolset for protein expression and subcellular localization studies in
citrus and its application to citrus tristeza virus proteins.
AB - Background: Transient gene expression is a powerful tool to study gene function
in plants. In citrus, Agrobacterium transformation is the method of choice for
transient expression studies, but this method does not work efficiently with many
gene constructs, and there is a need for a more robust transient expression
system in citrus leaves. Biolistic particle delivery is an alternative to
Agrobacterium transformation, and in some plants, such as Arabidopsis, gives
higher transformation rates in leaf tissues than Agrobacterium. Results: Here we
describe an improved method for gene expression in epidermal cells of citrus
leaves, using the Bio-Rad Helios gene-gun. Gene-gun bombardment of GFP-HDEL
produced highly efficient gene expression in large number of cells and in
different citrus varieties. We show here that transiently expressed proteins have
maintained their functions in plants, and this is demonstrated by the subcellular
localization of different organelle markers, and by a functional assay of
Xanthomonas citri effector AvrGF1. To further expand the available tools for
subcellular localization studies in citrus, we also generated a new set of
transgenic citrus plants that contain organelle markers labelling the nuclei,
actin and endoplasmic reticulum. Using these new tools, we were able to show that
the coat protein of citrus tristeza virus localizes to the cytoplasm and nuclei
when expressed in epidermal cells fused to GFP. Conclusion: We have optimized a
new method for transient expression in citrus leaves, to give highly reproducible
and efficient transformation without producing a high level of injury or
artifacts to the bombarded tissue. We also generated the first set organelle
markers for use in citrus. These fluorescent protein markers label the nucleus
and the actin. With these new resources, protein activity and subcellular
localization can be studied in citrus rapidly and in high throughput. The
handheld gene-gun device can also be used in the grove to deliver therapies for
citrus diseases, such as canker and Huanglongbing, into trees.
PMID- 29339970
TI - A new image-based tool for the high throughput phenotyping of pollen viability:
evaluation of inter- and intra-cultivar diversity in grapevine.
AB - Background: Low pollen viability may limit grapevine yield under certain
conditions, causing relevant economic losses to grape-growers. It is usually
evaluated by the quantification of the number of viable and non-viable pollen
grains that are present in a sample after an adequate pollen grain staining
procedure. Although the manual counting of both types of grains is the simplest
and most sensitive approach, it is a laborious and time-demanding process. In
this regard, novel image-based approaches can assist in the objective, accurate
and cost-effective phenotyping of this trait. Results: Here, we introduce
PollenCounter, an open-source macro implemented as a customizable Fiji tool for
the high-throughput phenotyping of pollen viability. This tool splits RGB images
of stained pollen grains into its primary channels, retaining red and green color
fractionated images (which contain information on total and only viable pollen
grains, respectively) for the subsequent isolation and counting of the regions of
interest (pollen grains). This framework was successfully used for the analysis
of pollen viability of a high number of samples collected in a large collection
of grapevine cultivars. Results revealed a great genetic variability, from
cultivars having very low pollen viability (like Corinto Bianco; viability: 14.1
+/- 1.3%) to others with a very low presence of sterile pollen grains (Cuelga;
viability: 98.2 +/- 0.5%). A wide range of variability was also observed among
several clones of cv. Tempranillo Tinto (from 97.9 +/- 0.9 to 60.6 +/- 5.9%, in
the first season). Interestingly, the evaluation of this trait in a second season
revealed differential genotype-specific sensitivity to environment. Conclusions:
The use of PollenCounter is expected to aid in different areas, including
genetics research studies, crop improvement and breeding strategies that need of
fast, precise and accurate results. Considering its flexibility, it can be used
not only in grapevine, but also in other species showing a differential staining
of viable and non-viable pollen grains. The wide phenotypic diversity observed at
a species level, together with the identification of specific cultivars and
clones largely differing in this trait, pave the way of further analyses aimed to
understand the physiological and genetic causes driving to male sterility in
grapevine.
PMID- 29339971
TI - Terzyme: a tool for identification and analysis of the plant terpenome.
AB - Background: Terpenoid hydrocarbons represent the largest and most ancient group
of phytochemicals, such that the entire chemical library of a plant is often
referred to as its 'terpenome'. Besides having numerous pharmacological
properties, terpenes contribute to the scent of the rose, the flavors of cinnamon
and the yellow of sunflowers. Rapidly increasing -omics datasets provide an
unprecedented opportunity for terpenome detection, paving the way for automated
web resources dedicated to phytochemical predictions in genomic data. Results: We
have developed Terzyme, a predictive algorithm for identification, classification
and assignment of broad substrate unit to terpene synthase (TPS) and prenyl
transferase (PT) enzymes, known to generate the enormous structural and
functional diversity of terpenoid compounds across the plant kingdom. Terzyme
uses sequence information, plant taxonomy and machine learning methods for
predicting TPSs and PTs in genome and proteome datasets. We demonstrate a
significant enrichment of the currently identified terpenome by running Terzyme
on more than 40 plants. Conclusions: Terzyme is the result of a rigorous analysis
of evolutionary relationships between hundreds of characterized sequences of TPSs
and PTs with known specificities, followed by analysis of genome-wide gene
distribution patterns, ontology based clustering and optimization of various
parameters for building accurate profile Hidden Markov Models. The predictive
webserver and database is freely available at http://nipgr.res.in/terzyme.html
and would serve as a useful tool for deciphering the species-specific
phytochemical potential of plant genomes.
PMID- 29339972
TI - Evaluation of green tea extract as a safe personal hygiene against viral
infections.
AB - Background: Viral infections often pose tremendous public health concerns as well
as economic burdens. Despite the availability of vaccines or antiviral drugs,
personal hygiene is considered as effective means as the first-hand measure
against viral infections. The green tea catechins, in particular,
epigallocatechin-3-gallate (EGCG), are known to exert potent antiviral activity.
In this study, we evaluated the green tea extract as a safe personal hygiene
against viral infections. Results: Using the influenza virus A/Puerto Rico/8/34
(H1N1) as a model, we examined the duration of the viral inactivating activity of
green tea extract (GTE) under prolonged storage at various temperature
conditions. Even after the storage for 56 days at different temperatures, 0.1%
GTE completely inactivated 106 PFU of the virus (6 log10 reduction), and 0.01%
and 0.05% GTE resulted in 2 log10 reduction of the viral titers. When
supplemented with 2% citric acid, 0.1% sodium benzoate, and 0.2% ascorbic acid as
anti-oxidant, the inactivating activity of GTE was temporarily compromised during
earlier times of storage. However, the antiviral activity of the GTE was steadily
recovered up to similar levels with those of the same concentrations of GTE
without the supplements, effectively prolonging the duration of the virucidal
function over extended period. Cryo-EM and DLS analyses showed a slight increase
in the overall size of virus particles by GTE treatment. The results suggest that
the virucidal activity of GTE is mediated by oxidative crosslinking of catechins
to the viral proteins and the change of physical properties of viral membranes.
Conclusions: The durability of antiviral effects of GTE was examined as solution
type and powder types over extended periods at various temperature conditions
using human influenza A/H1N1 virus. GTE with supplements demonstrated potent
viral inactivating activity, resulting in greater than 4 log10 reduction of viral
titers even after storage for up to two months at a wide range of temperatures.
These data suggest that GTE-based antiviral agents could be formulated as a safe
and environmentally friendly personal hygiene against viral infections.
PMID- 29339973
TI - One-step production of C6-C8 carboxylates by mixed culture solely grown on CO.
AB - Background: This study aimed at producing C6-C8 medium-chain carboxylates (MCCAs)
directly from gaseous CO using mixed culture. The yield and C2-C8 product
composition were investigated when CO was continuously fed with gradually
increasing partial pressure. Results: The maximal concentrations of n-caproate, n
heptylate, and n-caprylate were 1.892, 1.635, and 1.033 mmol L-1, which were
achieved at the maximal production rates of 0.276, 0.442, and 0.112 mmol L-1 day
1, respectively. Microbial analysis revealed that long-term acclimation and high
CO partial pressure were important to establish a CO-tolerant and CO-utilizing
chain-elongating microbiome, rich in Acinetobacter, Alcaligenes, and
Rhodobacteraceae and capable of forming MCCAs solely from CO. Conclusions: These
results demonstrated that carboxylate and syngas platform could be integrated in
a shared growth vessel, and could be a promising one-step technique to convert
gaseous syngas to preferable liquid biochemicals, thereby avoiding the necessity
to coordinate syngas fermentation to short-chain carboxylates and short-to-medium
chain elongation. Thus, this method could provide an alternative solution for the
utilization of waste-derived syngas and expand the resource of promising
biofuels.
PMID- 29339974
TI - Multidisciplinary treatment of patients with diabetes and hypertension:
experience of a Brazilian center.
AB - Background: Although multidisciplinary treatment is recommended for type 2
diabetes mellitus and hypertension (HTN), there is a lack of scientific
literature supporting the hypothesis of extending this treatment strategy to
patients with both diabetes and HTN. Aiming to report results of long-term
multidisciplinary treatment for these patients and identify strategies to improve
their management, we conducted this study. Methods: Data of patients with
diabetes and HTN with regular follow-up visits in a multidisciplinary HTN
treatment center from Brazil's Midwest were retrospectively assessed. Patients >=
18 years enrolled in the service by June 2017 with a minimum of three visits were
included. Anthropometric, blood pressure (BP), laboratory, pharmacological
treatment, lifestyle, and cardiovascular events data were collected from first
(V1), intermediate (V2) and most recent (V3) visits to the service. BP < 130 * 80
mmHg, LDL-cholesterol (LDL-C) < 70 mg/dL and HbA1C < 7.0% were defined as
treatment targets. Wilcoxon signed-rank test was used to compare variables along
study visits. A linear regression model was built to identify variables
associated with better overall patient control. Results: A total of 162 patients
were included (mean age of 56.5 +/- 10.8 years). Median follow-up time was 60
(IQR 40-109) months, 80.2% of the sample was female and 83.3% had no
cardiovascular event history. BP, total cholesterol, LDL-C, triglycerides and
HbA1C values showed a significant trend to improve along the study visits (p <
0.001). Growing trend in aspirin (p = 0.045) and statins (p < 0.001) use was
found, in addition to treatment compliance increase (p < 0.001). Significant
improvement trends in BP (p < 0.001), LDL-C (p = 0.004) and HbA1C (p = 0.002)
control were also found across visits. Control rates of BP, LDL-C and HbA1C in
combination were low in V1, V2 and V3 (1.2, 1.9 and 6.8%, respectively), but
showed significant improvement trend (p < 0.001). Treatment compliance (beta
coefficient = 1.20; 95% CI 1.07-1.34; p < 0.001) was positively associated with
better overall patients control. Conclusions: Multidisciplinary treatment of
patients with diabetes and HTN significantly improved clinical and laboratory
parameters, despite ageing of population evaluated. Although combined control of
HbA1C, BP and LDL-cholesterol increased along follow-up, management of all these
three conditions needs to improve, and focus on treatment compliance should be
given to attain this goal.
PMID- 29339975
TI - Genetic polymorphisms of antioxidant enzymes CAT and SOD affect the outcome of
clinical, biochemical, and anthropometric variables in people with obesity under
a dietary intervention.
AB - Background: Genetic polymorphisms of antioxidant enzymes CAT, GPX, and SOD are
involved in the etiology of obesity and its principal comorbidities. The aim of
the present study was to analyze the effect of aforementioned SNPs over the
output of several variables in people with obesity after a nutritional
intervention. The study included 92 Mexican women, which received a dietary
intervention by 3 months. Participants were genotyped and stratified into two
groups: (1) carriers; mutated homozygous plus heterozygous (CR) and (2)
homozygous wild type (WT). A comparison between CR and WT was done in clinical
(CV), biochemical (BV), and anthropometric variables (AV), at the beginning and
at the end of the intervention. Results: Participants (n = 92) showed
statistically significant differences (p < 0.05) at the end of the nutritional
intervention in several CV, BV, and AV. However, two kinds of responses were
observed after genotyping participants: (A) CR and WT showed statistically
significant differences (p < 0.05) in several CV, BV, and AV for the SNPs 599C>T
GPX1 (rs1050450), - 251A>G SOD1 (rs2070424), and - 262C>T CAT (rs1001179). (B)
Only CR showed statistically changes (p < 0.05) in several CV, BV, and AV for the
SNPs - 21A>T CAT (rs7943316) and 47C>T SOD2 (rs4880). The dietary intervention
effect was statistically significantly between the polymorphisms of 47C>T SOD2
and BMI, SBP, TBARS, total cholesterol, and C-LCL (p < 0.05) and between the
polymorphisms of - 21A>T CAT (rs7943316) and SBP, DBP, total cholesterol, and
atherogenic index (p < 0.05). Conclusion: People with obesity display different
response in several CV, BV, and AV after a nutritional intervention, depending on
the antioxidant genetic background of SOD and CAT enzymes.
PMID- 29339976
TI - Detection of dioxin-induced demethylation of mouse Cyp1a1 gene promoter by a new
labeling method for short DNA fragments possessing 5'-methylcytosine at the end.
AB - Environmental factors stimulate alteration of DNA methylation level.
Investigation of the genome-wide DNA methylation status is important for
environmental health studies. We here designed a genomic DNA amplification and
labeling protocol using a methylation-sensitive restriction enzyme HinP1 I. This
method can specifically amplify genomic DNA fragments possessing methyl-CpG at
the end. The fragments are a relatively short size and dominantly located on CpG
islands. By using the samples prepared by this method, a dioxin-induced change in
the methylation level of the mouse Cyp1a1 promoter was successfully evaluated
using oligonucleotide probes covalently bound onto a glass plate. The method
developed in this paper would be useful for other genome-wide analysis platforms
for the large scale epigenome-wide association studies (EWAS) including human
epidemiological samples.
PMID- 29339977
TI - Necessity for retrospective evaluation of past-positive chemicals in in vitro
chromosomal aberration tests using recommended cytotoxicity indices.
AB - We have demonstrated that retrospective evaluation of existing data of in vitro
chromosomal aberration test using the new cytotoxicity indices RICC (relative
increase in cell count) or RPD (relative population doubling) reduces the false
positive rate. We have constructed an algorithm to predict the likelihood that
past-positive results would differ when retested accordingly. Here, we emphasize
the importance of reviewing existing in vitro chromosomal aberration test
results. The present Letter not only supports the rediscovery of potentially
useful chemicals excluded from further development as a result of
misclassification due to in vitro false-positive results, but also contributes to
the development of a precise Quantitative Structure-Activity Relationship (QSAR)
model by providing an appropriate training data-set. Furthermore, re-evaluation
is expected to provide novel insights into underlying mechanisms and/or key
structures involved in the development of chromosomal aberrations.
PMID- 29339978
TI - Increase of somatic cell mutations in oxidative damage-sensitive drosophila.
AB - Background: Oxidative damage is an important genotoxic source for almost all
organisms. To efficiently detect mutations induced by oxidative damage, we
previously developed a urate-null Drosophila strain. Using this Drosophila
strain, we showed the mutagenic activity of environmental cigarette smoke (ECS)
and the herbicide paraquat, which are known to produce reactive oxygen species
(ROS). In the present study, we examined the mutagenic activities of carcinogenic
mutagens that are considered to cause mutations by adduct formation, alkylation,
or crosslinking of cellular DNA in the oxidative damage-sensitive Drosophila to
evaluate how the oxidative damage induced by these mutagens is involved in
causing mutations. In addition, we evaluated whether these oxidative damage
sensitive flies may be useful for mutation assays. Methods: We performed the wing
spot test in oxidative damage-sensitive Drosophila (urate-null strains) to
examine the mutagenicity of 2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline
(MeIQx), mitomycin C (MMC), 4-nitroquinoline N-oxide (4NQO), N-nitrosodimethyl
amine (NDMA), and N-nitrosodiethylamine (NDEA). We also observed the mutagenicity
of X-ray irradiation as a control in which mutations should be mainly caused by
oxidative damage. Results: As expected, the mutagenic activity of X-ray
irradiation was higher in the urate-null Drosophila than in the wild-type
Drosophila. The mutagenic activities of the tested compounds were also higher in
the urate-null Drosophila than in the wild-type Drosophila. In experiments using
another urate-null strain, the mutagenicity of N-nitrosodialkylamines was also
higher in the urate-null flies than in the wild-type ones. Conclusions: The
tested compounds in this study were more mutagenic in urate-null Drosophila than
in wild-type Drosophila. It was supposed that ROS were generated and that the ROS
might be involved in mutagenesis. The present results support the notion that in
addition to causing DNA lesions via adduct formation, alkylation, or DNA
crosslinking, these mutagens also cause mutations via ROS-induced DNA damage. As
such, urate-null Drosophila appear to be useful for detecting the mutagenic
activity of various mutagens, especially those that produce reactive oxygen. If
the mutation rate increases on a mutation assay using urate-null Drosophila, it
might suggest that the mutagen generates ROS, and that the produced ROS is
involved in causing mutations.
PMID- 29339980
TI - Re: The Integration of Internal and External Training Load Metrics in Hurling -
Interpretation Beyond a Significant Relationship Required.
PMID- 29339979
TI - BRCA1 and BRCA2 mutation spectrum - an update on mutation distribution in a large
cancer genetics clinic in Norway.
AB - Background: Founder mutations in the two breast cancer genes, BRCA1 and BRCA2,
have been described in many populations, among these are Ashkenazi-Jewish,
Polish, Norwegian and Icelandic. Founder mutation testing in patients with
relevant ancestry has been a cost-efficient approach in such populations. Four
Norwegian BRCA1 founder mutations were defined by haplotyping in 2001, and
accounted for 68% of BRCA1 mutation carriers at the time. After 15 more years of
genetic testing, updated knowledge on the mutation spectrum of both BRCA1 and
BRCA2 in Norway is needed. In this study, we aim at describing the mutation
spectrum and frequencies in the BRCA1/2 carrier population of the largest clinic
of hereditary cancer in Norway. Methods: A total of 2430 BRCA1 carriers from 669
different families, and 1092 BRCA2 carriers from 312 different families were
included in a quality of care study. All variants were evaluated regarding
pathogenicity following ACMG/ENIGMA criteria. The variants were assessed in
AlaMut and supplementary databases to determine whether they were known to be
founder mutations in other populations. Results: There were 120 different BRCA1
and 87 different BRCA2 variants among the mutation carriers. Forty-six per cent
of the registered BRCA1/2 families (454/981) had a previously reported Norwegian
founder mutation. The majority of BRCA1/2 mutations (71%) were rare, each found
in only one or two families. Fifteen per cent of BRCA1 families and 25% of BRCA2
families had one of these rare variants. The four well-known Norwegian BRCA1
founder mutations previously confirmed through haplotyping were still the four
most frequent mutations in BRCA1 carriers, but the proportion of BRCA1 mutation
carriers accounted for by these mutations had fallen from 68 to 52%, and hence
the founder effect was weaker than previously described. Conclusions: The
spectrum of BRCA1 and BRCA2 mutations in the carrier population at Norway's
largest cancer genetics clinic is diverse, and with a weaker founder effect than
previously described. As a consequence, retesting the families that previously
have been tested with specific tests/founder mutation tests should be a
prioritised strategy to find more mutation positive families and possibly prevent
cancer in healthy relatives.
PMID- 29339981
TI - Using Bilateral Functional and Anthropometric Tests to Define Symmetry in Cross
Country Skiers.
AB - The aim of this study was to evaluate the symmetry of anthropometry and muscle
function in cross-country skiers and their association to vertical jumping power.
Twenty cross-country skiers were recruited (21.7 +/- 3.8 yrs, 180.6 +/- 7.6 cm,
73.2 +/- 7.6 kg). Anthropometric data was obtained using an iDXA scan. VO2max was
determined using the diagonal stride technique on a ski treadmill. Bilateral
functional tests for the upper and lower body were the handgrip and standing heel
rise tests. Vertical jump height and power were assessed with a counter movement
jump. Percent asymmetry was calculated using a symmetry index and four absolute
symmetry index levels. At a group level the upper body was more asymmetrical with
regard to lean muscle mass (p = 0.022, d = 0.17) and functional strength (p =
0.019, d = 0.51) than the lower body. At an individual level the expected
frequencies for absolute symmetry level indexes showed the largest deviation from
zero for the heel-rise test (chi2 = 16.97, p = 0.001), while the leg lean mass
deviated the least (chi2 = 0.42, p = 0.517). No relationships were observed
between absolute symmetry level indexes of the lower body and counter movement
jump performance (p > 0.05). As a group the skiers display a more asymmetrical
upper body than lower body regarding muscle mass and strength. Interestingly at
the individual level, despite symmetrical lean leg muscle mass the heel-rise test
showed the largest asymmetry. This finding indicates a mismatch in muscle
function for the lower body.
PMID- 29339982
TI - Relationships between Mechanical Variables in the Traditional and Close-Grip
Bench Press.
AB - The study aim was to determine relationships between mechanical variables in the
one-repetition maximum (1RM) traditional bench press (TBP) and close-grip bench
press (CGBP). Twenty resistance-trained men completed a TBP and CGBP 1RM. The TBP
was performed with the preferred grip; the CGBP with a grip width of 95%
biacromial distance. A linear position transducer measured: lift distance and
duration; work; and peak and mean power, velocity, and force. Paired samples t
tests (p < 0.05) compared the 1RM and mechanical variables for the TBP and CGBP;
effect sizes (d) were also calculated. Pearson's correlations (r; p < 0.05)
computed relationships between the TBP and CGBP. 1RM, lift duration, and mean
force were greater in the TBP (d = 0.30-3.20). Peak power and velocity was
greater for the CGBP (d = 0.50-1.29). The 1RM TBP correlated with CGBP 1RM,
power, and force (r = 0.685-0.982). TBP work correlated with CGBP 1RM, lift
distance, power, force, and work (r = 0.542-0.931). TBP power correlated with
CGBP 1RM, power, force, velocity, and work (r = 0.484-0.704). TBP peak and mean
force related to CGBP 1RM, power, and force (r = 0.596-0.980). Due to
relationships between the load, work, power, and force for the TBP and CGBP, the
CGBP could provide similar strength adaptations to the TBP with long-term use.
The velocity profile for the CGBP was different to that of the TBP. The CGBP
could be used specifically to improve high-velocity, upper-body pushing
movements.
PMID- 29339983
TI - Analysis of the Hamstring Muscle Activation During two Injury Prevention
Exercises.
AB - The aim of this study was to perform an electromyographic and kinetic comparison
of two commonly used hamstring eccentric strengthening exercises: Nordic Curl and
Ball Leg Curl. After determining the maximum isometric voluntary contraction of
the knee flexors, ten female athletes performed 3 repetitions of both the Nordic
Curl and Ball Leg Curl, while knee angular displacement and electromyografic
activity of the biceps femoris and semitendinosus were monitored. No significant
differences were found between biceps femoris and semitendinosus activation in
both the Nordic Curl and Ball Leg Curl. However, comparisons between exercises
revealed higher activation of both the biceps femoris (74.8 +/- 20 vs 50.3 +/-
25.7%, p = 0.03 d = 0.53) and semitendinosus (78.3 +/- 27.5 vs 44.3 +/- 26.6%, p
= 0.012, d = 0.63) at the closest knee angles in the Nordic Curl vs Ball Leg
Curl, respectively. Hamstring muscles activation during the Nordic Curl
increased, remained high (>70%) between 60 to 40 degrees of the knee angle and
then decreased to 27% of the maximal isometric voluntary contraction at the end
of movement. Overall, the biceps femoris and semitendinosus showed similar
patterns of activation. In conclusion, even though the hamstring muscle
activation at open knee positions was similar between exercises, the Nordic Curl
elicited a higher hamstring activity compared to the Ball Leg Curl.
PMID- 29339984
TI - Functional vs. Traditional Analysis in Biomechanical Gait Data: An Alternative
Statistical Approach.
AB - In human motion studies, discrete points such as peak or average kinematic values
are commonly selected to test hypotheses. The purpose of this study was to
describe a functional data analysis and describe the advantages of using
functional data analyses when compared with a traditional analysis of variance
(ANOVA) approach. Nineteen healthy participants (age: 22 +/- 2 yrs, body height:
1.7 +/- 0.1 m, body mass: 73 +/- 16 kg) walked under two different conditions:
control and pain+effusion. Pain+effusion was induced by injection of sterile
saline into the joint capsule and hypertonic saline into the infrapatellar fat
pad. Sagittal-plane ankle, knee, and hip joint kinematics were recorded and
compared following injections using 2*2 mixed model ANOVAs and FANOVAs. The
results of ANOVAs detected a condition * time interaction for the peak ankle
(F1,18 = 8.56, p = 0.01) and hip joint angle (F1,18 = 5.77, p = 0.03), but did
not for the knee joint angle (F1,18 = 0.36, p = 0.56). The functional data
analysis, however, found several differences at initial contact (ankle and knee
joint), in the mid-stance (each joint) and at toe off (ankle). Although a
traditional ANOVA is often appropriate for discrete or summary data, in
biomechanical applications, the functional data analysis could be a beneficial
alternative. When using the functional data analysis approach, a researcher can
(1) evaluate the entire data as a function, and (2) detect the location and
magnitude of differences within the evaluated function.
PMID- 29339985
TI - Butterfly Sprint Swimming Technique, Analysis of Somatic and Spatial-Temporal
Coordination Variables.
AB - The aim of this study was to investigate somatic properties and force production
of leg extensor muscles measured in the countermovement jump test (CMJ), as well
as to analyse kinematic variables of sprint surface butterfly swimming. Thirty
four male competitive swimmers were recruited with an average age of 19.3 +/-
1.83 years. Their average body height (BH) was 183.7 +/- 5.93 cm, body fat
content 10.8 +/- 2.64% and body mass (BM) 78.3 +/- 5.0 kg. Length measurements of
particular body segments were taken and a counter movement jump (CMJ) as well as
an all-out 50 m butterfly speed test were completed. The underwater movements of
the swimmers' bodies were recorded with a digital camera providing side-shots. We
registered a significant relationship between body mass (r = 0.46), lean body
mass (r = 0.48) and sprint surface butterfly swimming (VSBF). The anaerobic power
measured in the CMJ test, total body length (TBL) as well as upper and lower
extremity length indices did not influence swimming speed significantly. The
temporal entry-kick index (the time ratio between the first kick and arm entry)
significantly influenced VSBF (r = -0.45). Similarly, medium power of the
coefficient was indicated between a) stroke rate kinematics (SR), b) duration of
the first leg kick (LP1), c) air phase duration of arm recovery (Fly-arm), and
VSBF (r = 0.40; r = 0.40 and r = 0.41, respectively). The entry-kick temporal
index showed that, in the butterfly cycle, an appropriately early executed
initial kick when compared to arm entry was associated with a longer arm
propulsion phase, which in turn was associated with minimizing resistive gliding
phases and enabled relatively longer and less resistive air arm recovery (higher
value of the fly-arm index). The higher value of SR kinematic was another
important element of the best butterfly results in this study.
PMID- 29339987
TI - Physiological Demands, Morphological Characteristics, Physical Abilities and
Injuries of Female Soccer Players.
AB - The popularity of female soccer is increasing as well as the number of females
playing soccer. Similarly, over the last twenty or so years, research in soccer
has increased significantly, but a large disparity exists in the volume of
studies involving male and female players. As a consequence of this, female
players remain less well understood compared to males. The purpose of the present
narrative review was to describe morphological characteristics, physiological
demands, physical abilities and injuries in female soccer players. Physiological
demands are similar between men's and women's soccer, but competitive women's
matches were characterized by nearly 33% less distance covered, although at
higher intensity levels (maximum speeds greater than 15 km/h) than typically
found in the men's game. Sub-elite female players also tended to run less at
higher intensity levels at the end of both halves in comparison with elite female
players. High intensity running is an important factor of success in soccer since
many critical moments of the game occur under this condition. The ability to
rapidly change direction also determined elite, sub-elite and amateur levels. The
implementation of functional training, which focused on soccer-specific drills
and plyometric exercises, to improve explosive power, may improve conditioning in
female soccer players as well as decrease the risk of injuries which was 3-8
times higher in females compared to males. This review presents an in-depth
overview of the most influential factors for determining success in female
soccer.
PMID- 29339986
TI - Seeking Optimal Nutrition for Healthy Body Mass Reduction among Former Athletes.
AB - The aim of the study was to investigate the efficacy of 6 week Mediterranean diet
or 30% calorie restriction on the fatty acid profile and eicosanoids
(hydroxyoctadecadienoi acids and hydroxyeicosatetraenoic acids) concentration.
Furthermore, basic biochemical variables such as insulin, glucose, HOMA-IR, and a
lipid profile were estimated. The study enrolled 94 Caucasian former athletes
aged 20-42, with body height of 179 +/- 16.00 cm and body mass of 89.26 +/- 13.25
kg who had not been active for at least 5 years. The subjects were randomly
assigned to one of the three intervention groups: CR group - the 30% calorie
restriction (n = 32), MD group - the Mediterranean diet (n = 34), and C group - a
control group (n = 28). The pattern of nutrition was analysed before and after
the experiment using the 72 h food diaries. In order to evaluate the effect of
diet intervention, the following variables were measured: anthropometrics, basic
biochemical variables (insulin, fasting glucose, HOMA-IR, lipid profile), fatty
acids and their blood derivatives profiles. The CR group showed significantly
lower levels of several biochemical variables, i.e., BMI, total cholesterol LDL,
TG, total lipids, insulin and HOMA - IR (p < 0.05). Subjects consuming the MD
diet significantly decreased their BMI and reduced the level of total lipids (p <
0.05). We did not find any significant changes in the C group. The analysis of
the fatty acid profile revealed that the CR group had a significantly decreased
EPA level (p < 0.05). The MD group showed a significantly increased level of the
DHA (p < 0.05) and improvement in the omega - 3 index (p < 0.05). Subjects
following the MD also showed significantly lower concentrations of 15 -
hydroxyicosatetraenoic acid (15-HETE). We did not observe any significant
differences between the CR and C groups. Within short time, calorie restriction
helps to improve lipid variables and insulin resistance. The MD diet seems to be
more advantageous in the decrease of inflammation, but does not improve basic
biochemical variables. We can conclude that calorie restriction can be a good
choice for former athletes, although EPA and DHA supplementation is needed.
PMID- 29339988
TI - Impact of Futsal and Swimming Participation on Bone Health in Young Athletes.
AB - Physical activity plays a crucial role in bone mass acquisition during childhood
and adolescence, with weightbearing and high-impact sport activities being more
beneficial. This study sought to evaluate the impact of different sports
activities on bone mineral density and content in male Portuguese athletes.
Seventy adolescent boys (aged 12-15 years) including 28 futsal players (FG), 20
swimmers (SG) and 22 non-athletic adolescents used as control subjects (CG),
participated in the current study. Areal bone mineral density (aBMD) and areal
bone mineral content (aBMC) were measured by dual energy x-ray absorptiometry
(DEXA). Futsal players had significantly higher aBMD (lumbar spine - FG: 0.95 +/-
0.18, SG: 0.80 +/- 0.13, CG: 0.79 +/- 0.13 g/cm2, p = 0.001; pelvis - FG: 1.17 +/
0.21, SG: 0.91 +/- 0.12, CG: 0.98 +/- 0.10 g/cm2, p < 0.001; lower limbs - FG:
1.21 +/- 0.19, SG: 0.97 +/- 0.10, CG: 0.99 +/- 0.09 g/cm2, p < 0.001) and aBMC
(lumbar spine - FG: 51.07 +/- 16.53, SG: 40.19 +/- 12.47, CG: 40.50 +/- 10.53 g,
p = 0.013; pelvis - FG: 299.5 +/- 110.61, SG: 170.02 +/- 55.82, CG: 183.11 +/-
46.78 g, p < 0.001; lower limbs - FG: 427.21 +/- 117.11, SG: 300.13 +/- 76.42,
CG: 312.26 +/- 61.86 g/cm2, p < 0.001) than swimmers and control subjects. Data
suggest that futsal, as a weightbearing and high or odd-impact sport, may improve
bone mass during childhood and adolescence.
PMID- 29339989
TI - Association between Match Activity Variables, Measures of Fatigue and
Neuromuscular Performance Capacity Following Elite Competitive Soccer Matches.
AB - The aim of the study was to assess the relationships between match activity
variables, subsequent fatigue and neuromuscular performance capacity in elite
soccer players. Subjects (n = 10) were professional soccer players participating
in the English Championships. Match activity variables and markers of fatigue
status were measured before and following two matches. Creatine kinase (CK) and
muscle soreness were measured at baseline, immediately following, as well as 40
and 64 h post-match. Countermovement jump performance and perceived ratings of
wellness were measured at baseline, then 40 and 64 h post-match. Relationships
were shown between CK and the total number of accelerations and decelerations
immediately (r = 0.63; large), 40 h (r = 0.45; moderate) and 64 h post-match (r =
0.35; moderate) (p < 0.05). Relationships between CK and total sprint distance (r
= 0.39; moderate) and the number of sprints (r = 0.35; moderate) 40 h post-match
(p < 0.05) were observed. Furthermore, relationships were shown between the
perceived rating of wellness and number of accelerations 40 (r = 0.52; large) and
64 h (r = 0.40; moderate) post-match, sprint distance 40 h post-match (r = 0.40;
moderate) and the total number of sprints 40 h post-match (r = 0.51; large) (p <
0.05). The quantification of match activity variables, particularly the total
number of accelerations and decelerations and the number of sprints, provides
insights into the fatigue status in elite soccer players 40 and 64 h post-match.
PMID- 29339990
TI - High-Intensity Small-Sided Games versus Repeated Sprint Training in Junior Soccer
Players.
AB - The aim of this study was to compare the effects of high-intensity small-sided
games training (SSGT) versus repeated-sprint training (RST) on repeated-sprint
ability (RSA), soccer specific endurance performance and short passing ability
among junior soccer players. The junior soccer players were recruited from of a
professional team (age 16.9 +/- 1.1 years). The tests included the repeated
shuttle-sprint ability test (RSSAT), Yo-Yo Intermittent Recovery Test level 1 (Yo
Yo IR1) and Loughborough Soccer Passing Test (LSPT). Nineteen participants were
randomly assigned to either the small-sided games training (SSGTG) (n = 10) or
repeated-sprint training group (RSTG) (n = 9). Small-sided games or repeated
sprint training were added to the regular training sessions for two days of the
regular practice week. The Wilcoxon signed-rank and Mann-Whitney U tests were
used to examine differences in groups and training effects. A time x training
group effect was found in the improvement of short-passing ability for the
smallsided games training group which showed significantly better scores than the
repeated-sprint training group (p <= 0.05). Both groups showed similar
improvements in RSAdecrement (p < 0.05). Only the repeated-sprint training group
improved in the Yo-Yo IR1 (p < 0.05). This study clearly shows that high
intensity small-sided games training can be used as an effective training mode to
enhance both repeated sprint ability and short-passing ability.
PMID- 29339991
TI - Multivariate Profiles of Selected versus Non-Selected Elite Youth Brazilian
Soccer Players.
AB - This study determined whether a multivariate profile more effectively
discriminated selected than non-selected elite youth Brazilian soccer players.
This examination was carried out on 66 youth soccer players (selected, n = 28,
mean age 16.3 +/- 0.1; non-selected, n = 38, mean age 16.7 +/- 0.4) using
objective instruments. Multivariate profiles were assessed through anthropometric
characteristics, biological maturation, tactical-technical skills, and motor
performance. The Student's t-test identified that selected players exhibited
significantly higher values for height (t = 2.331, p = 0.02), lean body mass (t =
2.441, p = 0.01), and maturity offset (t = 4.559, p < 0.001), as well as
performed better in declarative tactical knowledge (t = 10.484, p < 0.001),
shooting (t = 2.188, p = 0.03), dribbling (t = 5.914, p < 0.001), speed - 30 m (t
= 8.304, p < 0.001), countermovement jump (t = 2.718, p = 0.008), and peak power
tests (t = 2.454, p = 0.01). Forward stepwise discriminant function analysis
showed that declarative tactical knowledge, running speed -30 m, maturity offset,
dribbling, height, and peak power correctly classified 97% of the selected
players. These findings may have implications for a highly efficient selection
process with objective measures of youth players in soccer clubs.
PMID- 29339992
TI - Effects of Passive and Active Rest on Physiological Responses and Time Motion
Characteristics in Different Small Sided Soccer Games.
AB - The purpose of this study was to investigate the effects of resting regimes on
physiological responses and time motion characteristics between bouts during
small sided games (SSGs) in young soccer players. Sixteen players (average age
16.87 +/- 0.34 years; body height 176.69 +/- 3.21 cm; body mass 62.40 +/- 2.59
kg; training experience 3.75 +/- 0.44 years) performed four bouts 2-a-side, 3-a
side and 4-a-side games with three minutes active (SSGar: Running at 70% of
HRmax) and passive (SSGpr) rest between bouts at two-day intervals. The heart
rate (HR) along with total distance covered in different speed zones - walking
(W, 0-6.9 km.h-1), low-intensity running (LIR, 7.0-12.9 km.h-1), moderate
intensity running (MIR, 13.0-17.9 km.h-1) and high-intensity running (HIR,
>18km.h-1), were monitored during all SSGs, whereas the rating of perceived
exertion (RPE, CR-20) and venous blood lactate (La-) were determined at the end
of the last bout of each SSG. The results demonstrated that all SSGpr elicited
significantly higher physiological responses compared to SSGar in terms of the
RPE and La- (p < 0.05). In addition, 2-a-side SSGpr induced significantly lower
%HRmax responses and total distance covered than 2-a-side SSGar (p < 0.05).
Moreover, the distance covered at HIR was significantly higher in 4-a-side SSGar
than 4-side SSGpr. The results of this study indicate that both SSGs with passive
and active rest can be used for soccer specific aerobic endurance training.
Furthermore, all SSGs with active recovery should be performed in order to
increase players and teams' performance capacity for subsequent bouts.
PMID- 29339993
TI - Functional and Muscle-Size Effects of Flywheel Resistance Training with Eccentric
Overload in Professional Handball Players.
AB - The aim of the study was to analyse the effects of 6 week (15 sessions) flywheel
resistance training with eccentric-overload (FRTEO) on different functional and
anatomical variables in professional handball players. Twenty-nine athletes were
recruited and randomly divided into two groups. The experimental group (EXP, n =
15) carried out 15 sessions of FRTEO in the leg-press exercise, with 4 sets of 7
repetitions at a maximum-concentric effort. The control group (CON, n = 14)
performed the same number of training sessions including 4 sets of 7 maximum
repetitions (7RM) using a weight-stack leg-press machine. The results which were
measured included maximal dynamic strength (1RM), muscle power at different
submaximal loads (PO), vertical jump height (CMJ and SJ), 20 m sprint time (20
m), T-test time (T-test), and Vastus-Lateralis muscle (VL) thickness. The results
of the EXP group showed a substantially better improvement (p < 0.05-0.001) in
PO, CMJ, 20 m, T-test and VL, compared to the CON group. Moreover, athletes from
the EXP group showed significant improvements concerning all the variables
measured: 1RM (ES = 0.72), PO (ES = 0.42 - 0.83), CMJ (ES = 0.61), SJ (ES =
0.54), 20 m (ES = 1.45), T-test (ES = 1.44), and VL (ES = 0.63 - 1.64). Since
handball requires repeated short, explosive effort such as accelerations and
decelerations during sprints with changes of direction, these results suggest
that FRTEO affects functional and anatomical changes in a way which improves
performance in well-trained professional handball players.
PMID- 29339994
TI - The Second to Fourth Digit Ratio in Elite and Non-Elite Greco-Roman Wrestlers.
AB - A low second-to-fourth digit ratio (2D:4D) has been reported to correlate with
high performance and athletic potential of an individual in sport. It has been
suggested that 2D:4D is a relatively weak predictor of strength and a stronger
predictor of efficiency in aerobic exercise. Comparing extreme groups on a
continuum of sports performance requiring high power (physical strength) output
would be helpful to resolve this issue. Therefore, the purpose of the present
study was to compare the 2D:4D ratio of world-class elite Greco-Roman wrestlers
(n = 10) taking part in Olympic fitness camps in 2013 with the 2D:4D ratio of non
elite collegiate wrestlers (n = 20), and age-matched sedentary males (n = 40).
The 2D:4D ratios of elite wrestlers were lower compared to non-elite athletes (p
< 0.01, right hand d = 1.70, left hand d = 1.67) and the control group (p <
0.0001, right hand d = 3.16, left hand d = 2.00). No significant differences were
noted among the groups for right - left 2D:4D. We concluded that 2D:4D may
discriminate between non-elite and world-class wrestlers. We also suggest that a
low 2D:4D ratio could be linked to performance potential in wrestlers. As such,
2D:4D may provide additional information, which is valuable in determining the
potential athleticism of an individual, when it is used in conjunction with other
measures.
PMID- 29339995
TI - Physical Performance and Anthropometric Characteristics of Male South African
University Soccer Players.
AB - Soccer is the most popular sport worldwide. Despite its global acclaim,
scientific studies of soccer have tended to focus on tactics and techniques,
thereby neglecting the physical and physiological profile of the players.
Therefore, the purpose of this study was to examine physical and anthropometric
characteristics of male South African university soccer players. Twenty-seven
male soccer players aged 19 to 24 (mean age: 22.1 years; s = 1.5 years)
volunteered to participate in the study. The results showed that goalkeepers
(77.5 +/- 9.7 kg) and defenders (68.2 +/- 6.5 kg) were the heaviest compared to
players in other playing positions. The goalkeepers also had the highest
percentage of body fat (11.3 +/- 2.3%), in contrast to midfielders who had the
lowest body fat content (9.1 +/- 0.9%). With regard to flexibility, defenders
(45.1 +/- 4.9 cm) and midfielders (45.9 +/- 5.4 cm) performed better than
goalkeepers (37.1 +/- 4.3 cm) and strikers (40.1 +/- 3.4 cm). Midfielders (57.2
+/- 3.1 ml1.kg-1.min1) and defenders (56.1 +/- 5.1 ml1.kg-1.min1) had
significantly higher values of maximal oxygen uptake (VO2max) than goalkeepers
(47.9 +/- 0.2 ml-1.kg-1.min-1) and strikers (49.8 +/- 6.2 ml-1.kg-1.min-1). No
significant (p > 0.05) differences were observed for all other variables, with
the exception of body height, body mass, and VO2max. It was therefore concluded
that sports scientists and coaches should tailor conditioning programmes in
soccer according to players' positions in view of the implications for successful
performance.
PMID- 29339996
TI - Judging in Rhythmic Gymnastics at Different Levels of Performance.
AB - This study aimed to analyse the quality of difficulty judging in rhythmic
gymnastics, at different levels of performance. The sample consisted of 1152
difficulty scores concerning 288 individual routines, performed in the World
Championships in 2013. The data were analysed using the mean absolute judge
deviation from the final difficulty score, a Cronbach's alpha coefficient and
intra-class correlations, for consistency and reliability assessment. For
validity assessment, mean deviations of judges' difficulty scores, the Kendall's
coefficient of concordance W and ANOVA eta-squared values were calculated.
Overall, the results in terms of consistency (Cronbach's alpha mostly above 0.90)
and reliability (intra-class correlations for single and average measures above
0.70 and 0.90, respectively) were satisfactory, in the first and third parts of
the ranking on all apparatus. The medium level gymnasts, those in the second part
of the ranking, had inferior reliability indices and highest score dispersion. In
this part, the minimum of corrected item-total correlation of individual judges
was 0.55, with most values well below, and the matrix for between-judge
correlations identified remarkable inferior correlations. These findings suggest
that the quality of difficulty judging in rhythmic gymnastics may be compromised
at certain levels of performance. In future, special attention should be paid to
the judging analysis of the medium level gymnasts, as well as the Code of Points
applicability at this level.
PMID- 29339997
TI - The Relative Age Effect on Soccer Players in Formative Stages with Different
Sport Expertise Levels.
AB - The Relative Age Effect (RAE) in sport has been targeted by many research
studies. The objective of this study was to analyze, in amateur clubs, the RAE of
soccer players, according to the sport expertise level of the team (e.g., A, B, C
and subsequent) that they belong to within the same game category. 1,098 soccer
players in formative stages took part in the study, with ages varying between 6
and 18 years old (U8 to U19 categories). All of them were members of 4 Spanish
federated clubs. The birth dates were classified into 4 quartiles (Q1 = Jan-Mar;
Q2 = Apr-Jun; Q3 = Jul-Sept; Q4 = Oct-Dec)according to the team they belonged to.
The results obtained in the chi-squared test and d value (effect size) revealed
the existence of RAE in the teams with the highest expertise level, "A" (X2 =
15.342, p = .002, d = 0.4473) and "B" (X2 = 10.905, p = .012, d = 0.3657).
However, in the lower level teams, "C and subsequent", this effect was not
observed. Present findings show that players born during the first months of the
year tend to be selected to play in teams with a higher sport expertise level of
each category, due to their physical maturity. Consequently, this causes
differences in terms of the experience they accumulate and the motivation that
this creates in these players.
PMID- 29339998
TI - Planning Training Loads for the 400 M Hurdles in Three-Month Mesocycles using
Artificial Neural Networks.
AB - This paper presents a novel approach to planning training loads in hurdling using
artificial neural networks. The neural models performed the task of generating
loads for athletes' training for the 400 meters hurdles. All the models were
calculated based on the training data of 21 Polish National Team hurdlers, aged
22.25 +/- 1.96, competing between 1989 and 2012. The analysis included 144
training plans that represented different stages in the annual training cycle.
The main contribution of this paper is to develop neural models for planning
training loads for the entire career of a typical hurdler. In the models, 29
variables were used, where four characterized the runner and 25 described the
training process. Two artificial neural networks were used: a multi-layer
perceptron and a network with radial basis functions. To assess the quality of
the models, the leave-one-out cross-validation method was used in which the
Normalized Root Mean Squared Error was calculated. The analysis shows that the
method generating the smallest error was the radial basis function network with
nine neurons in the hidden layer. Most of the calculated training loads
demonstrated a non-linear relationship across the entire competitive period. The
resulting model can be used as a tool to assist a coach in planning training
loads during a selected training period.
PMID- 29339999
TI - Reliability and Usefulness of the 30-15 Intermittent Fitness Test in Male and
Female Professional Futsal Players.
AB - The purpose of this study was to determine the reliability and usefulness of the
30-15 Intermittent Fitness Test (30-15IFT) in professional male and female futsal
players. Thirteen male (24.4 +/- 5.6 years; 174.5 +/- 10.3 cm; 70.3 +/- 9.9 kg)
and fourteen female (23.3 +/- 4.5 years; 165.8 +/- 6.2 cm; 61.7 +/- 5.5 kg)
professional futsal players performed the 30-15IFT on two occasions, separated by
5 days. Maximal intermittent running velocity (VIFT) and heart rate at exhaustion
(HRpeak) data were collected for both tests. Reliability was assessed by the
intraclass correlation coefficient (ICC), typical error (TE) expressed as a
coefficient of variation (CV), and smallest worthwhile change (SWC). VIFT
demonstrated very good reliability between sessions, both for male (ICC = 0.92)
and female (ICC = 0.96) players. As the TE for VIFT and HRpeak was similar to the
calculated SWC for both male and female players, the usefulness of the test was
rated as "medium". A change in performance of at least 2 stages in male players,
or a change of more than 1 stage in female players could be interpreted as a
meaningful change in aerobic futsal fitness. The results of this study
demonstrate that the 30-15IFT is both a reliable and useful test for male and
female professional futsal players.
PMID- 29340000
TI - Sprinting, Change of Direction Ability and Horizontal Jump Performance in Youth
Runners According to Gender.
AB - The purpose of the study was to assess straight sprinting, change of direction
ability and horizontal jump performance in youth runners according to age and
gender. Two hundred and fifty-five youth runners (116 boys and 139 girls)
participated in this study. The athletes were divided according to their age into
five groups: under 8 yr (U8), under 10 yr (U10), under 12 yr (U12), under 14 yr
(U14) and under 16 yr (U16). Significant differences (p < 0.01) were found
between U8 and U10 in the 5 m sprint (d = 1.22), 505 agility test (505, d =
0.96), modified agility test (MAT, d = 1.43), horizontal countermovement jump
(HCMJ, d = 1.06) and arm swing HCMJ (HCMJAS, d = 1.44); between U10 and U12 in
the 505 (d = 0.39), MAT (d = 0.74), HCMJ (d = 0.96) and HCMJAS (d = 0.75); and
between U12 and U14 in 5 m (d = 0.84), HCMJ (d = 0.88) and HCMJAS (d = 0.79).
However, no significant differences (p > 0.05, d = 0.29-1.17) between U14 and U16
were observed in any of the tests. With regard to age and gender, in U8 and U10
groups there were no significant differences (p > 0.05, d = 0.02-0.76) between
boys and girls in any test. However, in U12 and U14 groups, significant gender
differences (p < 0.05, d = 0.85-1.24) were found in the MAT. Likewise, the boys
obtained better results than girls in the horizontal jump tests (p < 0.05, d =
1.01-1.26). After the classification by age, some differences were observed
between both genders, depending on the fitness variable evaluated.
PMID- 29340001
TI - Neuromuscular Control During the Bench Press Movement in an Elite Disabled and
Able-Bodied Athlete.
AB - The disabled population varies significantly in regard to physical fitness, what
is conditioned by the damage to the locomotor system. Recently there has been an
increased emphasis on the role of competitive sport in enhancing health and the
quality of life of individuals with disability. One of the sport disciplines of
Paralympics is the flat bench press. The bench press is one of the most popular
resistance exercises used for the upper body in healthy individuals. It is used
not only by powerlifters, but also by athletes in most strength-speed oriented
sport disciplines. The objective of the study was to compare neuromuscular
control for various external loads (from 60 to 100% 1RM) during the flat bench
press performed by an elite able-bodied athlete and an athlete with lower limb
disability. The research project is a case study of two elite bench press
athletes with similar sport results: an able-bodied athlete (M.W., age 34 years,
body mass 103 kg, body height 1.72 m, 1RM in the flat bench press 200 kg) and a
disabled athlete (M.T., age 31 years, body mass 92 kg, body height 1.70 m, 1RM in
the flat bench press 190 kg). The activity was recorded for four muscles:
pectoralis major (PM), anterior deltoid (AD), as well as for the lateral and long
heads of the triceps brachii (TBlat and TBlong). The T-test revealed
statistically significant differences between peak activity of all the considered
muscles (AD with p = 0.001; PM with p = 0.001; TBlat with p = 0.0021 and TBlong
with p = 0.002) between the 2 athletes. The analysis of peak activity differences
of M.W and M.T. in relation to the load revealed statistically significant
differences for load changes between: 60 to 100% 1RM (p = 0.007), 70 to 100% 1RM
(p = 0.016) and 80 to 100% 1RM (p = 0.032). The flat bench press performed
without legs resting firmly on the ground leads to the increased engagement of
upper body muscles and to their greater activation. Isolated initial positions
can be used to generate greater engagement of muscle groups during the bench
press exercise and evoke their higher activation.
PMID- 29340002
TI - Performance Changes of Elite Paralympic Judo Athletes During a Paralympic Games
Cycle: A Case Study with the Brazilian National Team.
AB - The aim of this study was to describe the variations in power performance of
elite Paralympic judo athletes across three consecutive training cycles of
preparation for the ParaPan American Games, the World Championship and the
Paralympic Games. Eleven Paralympic judokas from the Brazilian National team
participated in this study. They were repeatedly assessed using squat and
countermovement jumps, mean propulsive power (MPP) in the jump-squat (JS), the
bench press and prone bench pull at several moments of the preparation. Training
supervision based on the optimum power zone (range of loads where power
production is maximized) was provided in the final cycle, prior to the Paralympic
Games. Magnitude-based inference was used to compare the repeated measurements of
power performance. Lower and upper limb muscle power gradually increased
throughout the cycles; however, the best results in all exercises were observed
prior to the Paralympic Games, during which the team won four silver medals. As
an illustration, prior to participation in the Paralympic Games the MPP in the JS
was likely to very likely higher than prior to the World Championship (effect
size [ES] = 0.77) and ParaPan American Games (ES = 0.53), and in January and
March 2016 (ES = 0.98 and 0.92, respectively; months preceding the Paralympic
Games). Power performance assessments can provide information about the evolution
of Paralympic judokas, and training at the optimum power zone seems to constitute
an effective method to improve lower and upper limb power in these athletes.
PMID- 29340003
TI - Sports Activity Following Cementless Metaphyseal Hip Joint Arthroplasty.
AB - An adequate level of physical activity has a substantial effect on both mental
and physical human health. Physical activity is largely dependent on the function
of the musculoskeletal and articular system. One of the most frequent diseases of
this system is degenerative joint disease. Due to the changing and more demanding
lifestyles and patients' willingness to be involved in sports activity, the
expectations of hip joint arthroplasty are becoming increasingly high.
Alleviating pain ceases to be the only reason for which patients choose surgical
interventions, while the expectations often include involvement in various
sports. Only few studies contain recommendations concerning the frequency, type
and intensity of sports activity which are acceptable after hip joint
arthroplasty. The aim of the study was to evaluate function and physical activity
of people following cementless short-stem hip joint arthroplasty in the
observation of at least five years. The study group comprised 106 patients who
underwent total hip arthroplasty due to degenerative joint diseases, chosen
according to inclusion criteria. Patients underwent routine physical examinations
following the Harris Hip Score protocol, responded to the UCLA scale and
questionnaires concerning pre-surgical and current physical activity. Our results
demonstrated that hip joint arthroplasty in people suffering from degenerative
joint diseases has a beneficial effect on their level of functioning and physical
activity. Although physical activity and the level of functioning obviously
reduced as a person aged, the level of physical activity continued to be very
high in both groups, with function of the hip joint evaluated as very good.
PMID- 29340004
TI - Performance and Kinematic Differences in Putting between Healthy and Disabled
Elite Golfers.
AB - Golfers with disability are limited in the execution of the full golf swing, but
their performance in putting may be comparable because this stroke does not
demand significant strength, balance and range of motion. Therefore, the aim of
this study was to compare putting performance, kinetic and kinematic consistency
between golfers with different disabilities and healthy athletes. The
participants consisted of three disabled athletes (perinatal cerebral palsy,
multiple sclerosis, below knee lower limb amputee) and three healthy golfers (age
34 +/- 4.5 years, body height 178 +/- 3.3 cm, body mass 83 +/- 6.2 kg). The
golfers' movements were recorded by active 3D markers for kinematic analyses; the
subjects performed 10 trials of a 6 m putting task while standing on separate
force platforms placed under each lower limb. Putting performance was measured by
the distance of the final ball position to the centre of the hole. ANOVA analyses
did not show any differences in clubhead speed and total ball distance from the
hole. The consistency of those two parameters expressed by the coefficient of
variation (CV) was CV = 0.5% or better in both groups for clubhead speed and
ranged from CV = 0.40 to 0.61% in healthy and CV = 0.21 to 0.55% in disabled
athletes for total error distance. The main effect ANOVA showed differences in
weight shift, hip and shoulder kinematics (p < 0.05) between healthy players and
all players with disability. All disabled athletes shifted their weight toward
the healthy side (towards the healthy lower limb) and alternated the end of the
swing. The player with below knee amputation had the lowest range of motion in
the shoulder joint during the putting stroke. The players with perinatal cerebral
palsy and multiple sclerosis had the largest range of motion in the hips. Putting
performance of disabled golfers was similar to healthy athletes. During training
of disabled players, coaches should pay attention to the specificity of a
particular disability when focused on putting performance. However, individual
technique should achieve the same consistency as observed in healthy players.
PMID- 29340005
TI - Comparison of Aerobic Performance Testing Protocols in Elite Male Wheelchair
Basketball Players.
AB - In wheelchair sports, aerobic performance is commonly assessed with the use of an
arm crank ergometer (ACE), a wheelchair ergometer (WCE) or a wheelchair treadmill
(WCT). There are different protocols to identify peak oxygen uptake in wheelchair
sports; however, only a few protocols have been applied to evaluate these
conditions in wheelchair basketball players. The purpose of this study was to
compare physiological responses during maximal exercise testing with the use of
ACE and WCT in wheelchair basketball players. Twelve elite male wheelchair
basketball players participated in this study. The research was performed during
a training camp of the Polish National Wheelchair Basketball Team. The study
participants were divided into two functional categories: A (players with class
1.0 - 2.5) and B (players with class 3.0 - 4.5). Two main maximal exercise tests,
i.e. wheelchair treadmill stress test (WCT test) and arm crank ergometer stress
test (ACE test) were used to evaluate aerobic performance of the players. There
were no statistically significant differences in aerobic tests between the
players from both groups. The comparison of results achieved in two aerobic tests
performed on WCT and ACE did not reveal any significant differences between the
analyzed variables (peak heart rate (HRpeak), peak oxygen uptake (VO2peak),
minute ventilation (VE), anaerobic threshold (AT), lactate concentration
(LApeak), and a drop in lactate concentration (%LA)). Strong correlations between
results achieved in WCT and ACE tests were found for VO2peak, VE and LApeak. The
main conclusion of the study is that both WCT and ACE tests may be useful when
determining aerobic capacity of wheelchair basketball players. Moreover, both
protocols can be used by athletes regardless of their functional capabilities and
types of impairment.
PMID- 29340006
TI - The Impact of the Progressive Efficiency Test on a Rowing Ergometer on White
Blood Cells Distribution and Clinical Chemistry Changes in Paralympic Rowers
During the Preparatory Stage Before the Paralympic Games in Rio, 2016 - A Case
Report.
AB - There is a large gap in knowledge regarding research on post-exercise blood
changes in disabled athletes. There are relatively few data on adaptive
mechanisms to exercise in disabled athletes, including disabled rowers. Two
rowers from a Polish adaptive rowing settle TAMix2x that qualified for the
Paralympic Games in Rio, 2016 took part in this study. They performed a
progressive test on a rowing ergometer until exhaustion. The cardiorespiratory
fitness measures, complete blood count, white blood cells' distribution and 30
clinical chemistry variables describing laboratory diagnostic profiles and
general health were determined. The extreme effort induced changes in all studied
metabolites (glucose, creatinine, urea, uric acid, total and direct bilirubin),
albumin, total protein levels in both participants. Furthermore, a post-exercise
increase in aspartate transaminase activity, yet a 2-fold decrease during the
recovery time in both rowers were found. White blood cell count increased 2-fold
after the test. The percentages of natural killer cells were higher and total T
lymphocytes were lower after the exercise protocol. There were higher percentages
of suppressor/cytotoxic and lower percentages of helper/inducer T lymphocyte
subsets in both studied rowers. No changes in B lymphocytes distribution were
observed. Lack of inflammatory symptoms during the experiment suggests a high
level of rowers' biological adaptation to the physical effort. The different
changes in physiological, biochemical and immunological variables are related to
the adaptive mechanism to physical exercise allowing for improvement of
performance.
PMID- 29340008
TI - Chemotherapy-induced metastasis in breast cancer.
PMID- 29340007
TI - Genomic insights into Mycobacterium simiae human colonization.
AB - Mycobacterium simiae (Karassova V, Weissfeiler J, Kraszanay E, Acta Microbiol
Acad Sci Hung 12:275-82, 1965) is a slow-growing nontuberculous Mycobacterium
species found in environmental niches, and recently evidenced as an opportunistic
Human pathogen. We report here the genome of a clinical isolate of M. simiae
(MsiGto) obtained from a patient in Guanajuato, Mexico. With a size of 6,684,413
bp, the genomic sequence of strain MsiGto is the largest of the three M. simiae
genomes reported to date. Gene prediction revealed 6409 CDSs in total, including
6354 protein-coding genes and 52 RNA genes. Comparative genomic analysis
identified shared features between strain MsiGto and the other two reported M.
simiae genomes, as well as unique genes. Our data reveals that M. simiae MsiGto
harbors virulence-related genes, such as arcD, ESAT-6, and those belonging to the
antigen 85 complex and mce clusters, which may explain its successful transition
to the human host. We expect the genome information of strain MsiGto will provide
a better understanding of infective mechanisms and virulence of this emergent
pathogen.
PMID- 29340009
TI - What is changing in the adjuvant treatment of melanoma?
PMID- 29340010
TI - Elongation vs stalling: place your BET.
PMID- 29340011
TI - Capecitabine for primary breast cancer.
PMID- 29340012
TI - Biomarkers in colorectal cancer screening.
PMID- 29340013
TI - The small molecule SI113 synergizes with mitotic spindle poisons in arresting the
growth of human glioblastoma multiforme.
AB - Glioblastoma multiforme (GBM) is the deadliest brain tumor. State-of-art GBM
therapy often fails to ensure control of a disease characterized by high
frequency of recurrences and progression. In search for novel therapeutic
approaches, we assayed the effect of compounds from a cancer drug library on the
ADF GBM cell line, establishing their elevated sensitivity to mitotic spindle
poisons. Our previous work showed that the effectiveness of the spindle poison
paclitaxel in inhibiting cancer cell growth was dependent on the expression of
RANBP1, a regulatory target of the serine/threonine kinase SGK1. Recently, we
developed the small molecule SI113 to inhibit SGK1 activity. Therefore, we
explored the outcome of the association between SI113 and selected spindle
poisons, finding that these drugs generated a synergistic cytotoxic effect in GBM
cells, drastically reducing their viability and clonogenic capabilities in vitro,
as well as inhibiting tumor growth in vivo. We also defined the molecular bases
of such a synergistic effect. Because SI113 displays low systemic toxicity, yet
strong activity in potentiating the effect of radiotherapy in GBM cells, we
believe that this drug could be a strong candidate for clinical trials, with the
aim to add it to the current GBM therapeutic approaches.
PMID- 29340014
TI - Cymbopogon citratus and Camellia sinensis extracts selectively induce apoptosis
in cancer cells and reduce growth of lymphoma xenografts in vivo.
AB - Cancer cells are reported to have elevated levels of reactive oxygen species
(ROS) and are highly dependent on cellular defense mechanisms against oxidative
stress. Numerous nutraceuticals and natural polyphenolic compounds have a wide
range of abilities to alter cellular redox states with potential implications in
various diseases. Furthermore, therapeutic options for cancers are mostly
nonselective treatments including genotoxic or tubulin-targeting compounds. Some
of the natural extracts, containing multiple bioactive compounds, could target
multiple pathways in cancer cells to selectively induce cell death. Cymbopogon
citratus (lemongrass) and Camellia sinensis (white tea) extracts have been shown
to have medicinal properties, however, their activity against lymphoma and
leukemia, as well as mechanistic details, have not been fully characterized.
Herein, we report potent anti-cancer properties in dose and time-dependent
manners of ethanolic lemongrass and hot water white tea extracts in lymphoma and
leukemia models. Both extracts were able to effectively induce apoptosis
selectively in these human cancer cell types. Interestingly, ethanolic lemongrass
extract induces apoptosis primarily by the extrinsic pathway and was found to be
dependent on the generation of ROS. Conversely, apoptotic induction by hot water
white tea extract was independent of ROS. Furthermore, both of these extracts
caused mitochondrial depolarization and decreased rates of oxygen consumption in
lymphoma and leukemia cells, leading to cell death. Most importantly, both these
extracts were effective in reducing tumor growth in human lymphoma xenograft
models when administered orally. Thus, these natural extracts could have
potential for being nontoxic alternatives for the treatment of cancer.
PMID- 29340015
TI - Apatinib alone or combined with radiotherapy in metastatic prostate cancer:
Results from a pilot, multicenter study.
AB - Background: To study safety and efficacy of apatinib in combination of
radiotherapy in patients with symptomatic bony disease prostate cancer(SBPC),
based on the potential synergistic antitumor activity between apatinib and
Radiation Therapy (RT). Patients and methods: In phase I dose escalation part, 18
patients received apatinib dose at 250 mg every other day, 250 mg daily and 500
mg daily. In phase II part, the 250 mg daily cohorts were expanded to 20 patients
in combination of RT (6 Gy/fraction, 5 fraction in total), one patient lost
followed up and excluded the study, comparing with RT alone cohort with 10
patients, ratio of RT to RT + apatinib was 1 to 2. Evaluations included adverse
events (AEs), prostate specific antigen (PSA) changes, radiographic evaluation
and pain relief. Results: In phase I study, common apatinib-related AEs (arAEs)
were fatigue, anorexia, hand foot syndrome, proteinuria, and hypertension (HTN).
Grade 3arAEs included HTN, proteinuria, liver dysfunction. In phase II study,
combination apatinib with RT cohorts, AEs events increased comparing with either
apatinib alone or RT alone; at the same time, combination cohorts showed PSA
declines of >=50% in 12 patients, and stable disease in 6 patients. Combination
cohorts had pain control significantly improved in both level and duration
comparing with RT alone. Conclusions: In SBPC patients, apatinib at less than 500
mg daily dose as mono-therapy had tolerable toxicity. Apatinib at dose of 250 mg
daily in combining with RT synergized pain control, the overall AEs were
manageable. Further studies are needed in large sample size future trials.
PMID- 29340016
TI - MiR-19 regulates the proliferation and invasion of glioma by RUNX3 via beta
catenin/Tcf-4 signaling.
AB - Accumulating data demonstrates that the network dysregulation of microRNA
medicated target genes is involved in glioma. We have previously found miR-19a/b
overexpression in glioma cell lines and specimens with various tumour grades.
However, there was no report on the function and regulatory mechanism of miR
19a/b in glioma. In this study, based on our previous research data, we first
determine the inverse relationship between miR-19 (miR-19a and miR-19b) and RUNX3
which is also identified the reduced expression in tumour tissues by real-time
PCR and IHC. Luciferase reporter assay and western blot analysis revealed that
RUNX3 was a direct target of miR-19. Down-regulation of miR-19 dramatically
inhibited proliferation, invasion and induced the cell cycle G1 arrest and
apoptosis, at least partly via the up-regulation of RUNX3. Furthermore,
Mechanistic investigation indicated that knockdown of miR-19 repressed the beta
catenin/TCF4 transcription activity. In conclusion, our study validates a
pathogenetic role of miR-19 in glioma and establishes a potentially regulatory
and signaling involving miR-19 /RUNX3/beta-catenin, also suggesting miR-19 may be
a candidate therapeutic target in glioma.
PMID- 29340017
TI - Altered GNAS imprinting due to folic acid deficiency contributes to poor embryo
development and may lead to neural tube defects.
AB - Disturbed epigenetic modifications have been linked to the pathogenesis of Neural
Tube Defects (NTDs) in those with folate deficiency during pregnancy. However,
evidence is lacking to delineate the critical region in epigenome regulated by
parental folic acid and mechanisms by which folate deficiency affects normal
embryogenesis. Our data from clinical samples revealed the presence of aberrant
DNA methylation in GNAS imprinting cluster in NTD samples with low folate
concentrations. Results from mouse models indicated that the establishment of
GNAS imprinting was influenced by both maternal and paternal folate-deficient
diets. Such aberrant GNAS imprinting was present prior to the gametogenesis
period. Imprinting in Exon1A/GNAS gDMR was abolished in both spermatozoa and
oocytes upon treating with a parental folate-deficient diet (3.6% in spermatozoa,
9.8% in oocytes). Interestingly, loss of imprinting in the GNAS gene cluster
altered chromatin structure to an overwhelmingly open structure (58.48% in the
folate-free medium group vs. 39.51% in the folate-normal medium group; P < 0.05),
and led to a disturbed expression of genes in this region. Furthermore, an
elevated cyclic AMP levels was observed in folate acid deficiency group. Our
results imply that GNAS imprinting plays major roles in folic acid metabolism
regulation during embryogenesis. Aberrant GNAS imprinting is an attribute to
NTDs, providing a new perspective for explaining the molecular mechanisms by
which folate supplementation in human pregnancy provides protection from NTDs.
PMID- 29340018
TI - Survival prediction of kidney renal papillary cell carcinoma by comprehensive
LncRNA characterization.
AB - Kidney renal papillary cell carcinoma (KIRP) accounts for 10%-15% of renal cell
carcinoma (RCC), patients with KIRP tend to have a poor prognosis, and there was
a lack of effective prognostic indicators for this type of cancer. Currently,
owing to the availability of The Cancer Genome Atlas (TCGA), long non-coding RNAs
(LncRNAs) have been discovered to indicate a prognostic value in some tumors. In
that regard, we analyzed lncRNA-sequencing data of KIRP in TCGA, and among 780
differentially-expressed lncRNAs, we selected 37 lncRNAs which were able to
assist the prognosis. In addition, by using the multivariate cox regression
analysis, the prognosis index (PI) that consisted of 7 lncRNAs (including AFAP1
AS1, GAS6-AS1, RP11-1C8.7, RP11-21L19.1, RP11-503C24.1, RP11-536I6.2, and RP11
63A11.1) could predict the progression and outcomes of KIRP with accuracy. More
importantly, the PI was considered an independent indicator for prognostication
of KIRP. Moreover, having categorized patients with KIRP into cohorts of high
risk and low risk, according to the PI, we found that the key genes and pathways
varied in these two groups. Overall, these LncRNAs, especially the PI, may be
conceived as biomarkers and helpful for determining the different pathological
stages for KIRP patients. However, their biological functions need to be further
confirmed.
PMID- 29340019
TI - Yonsei criteria: a clinical reflection of stage I left-sided pancreatic cancer.
AB - In this study, we examined associations between pancreatic cancer that met the
Yonsei criteria (YC) and classifications from the 8th edition of the American
Joint Committee on Cancer (AJCC) staging system. Clinicopathological and survival
data were collected from132 patients who underwent distal pancreatectomy for left
sided pancreatic ductal adenocarcinoma between January 2000 and December 2015,
and the utility of the YC for selecting treatment and predicting survival was
evaluated using the 8th AJCC staging manual. Of the 102 patients who ultimately
qualified for the study, 45 patients were reclassified as stage I based on the
8th AJCC cancer staging system. Disease-free survival and disease-specific
survival periods were longer in stage I patients who met the YC than in those who
did not. Clinicopathological characteristics did not differ between stage I
patients who did and did not meet the YC. These results suggest that meeting the
YC criteria may be a clinical indicator that left-sided pancreatic cancer
patients who are candidates for resection have early-stage disease according to
the 8th edition of the AJCC staging manual.
PMID- 29340020
TI - EYA2 promotes lung cancer cell proliferation by downregulating the expression of
PTEN.
AB - Lung cancer is the leading cause of cancer-related death worldwide. Despite
advances have been made in diagnosis and therapeutic strategies, the prognosis of
lung cancer is still very poor. Eyes absent transcriptional cofactor EYA2 has
been shown to promote lung cancer cell growth, however, the underlying molecular
mechanism is still not fully understood. In the present study, we found that EYA2
was up-regulated in lung cancer, and EYA2 led to increased cell proliferation by
inhibiting Phosphatase and tensin homologue (PTEN) expression via modulation of
miR-93. Additionally, survival analysis showed that lung cancer patients with
higher EYA2 expression predicted a worse prognosis. Therefore, these findings
demonstrate that EYA2 may play an important role in lung cancer occurrence and
progression. Targeting EYA2 may provide a feasible approach in developing novel
anticancer therapeutics.
PMID- 29340022
TI - A functional polymorphism of SSBP1 gene predicts prognosis and response to
chemotherapy in resected gastric cancer patients.
AB - Growing evidence has indicated that single-stranded DNA-binding proteins 1
(SSBP1) is involved in tumor initiation and progression. However, effects of
single nucleotide polymorphisms (SNPs) in SSBP1 gene on gastric cancer (GC)
prognosis are still unknown. In present study, two functional SNPs from SSBP1
were selected and genotyped in a large cohorts of 1030 resected GC patients (326
in the training set, 704 in the validation set) to explore the association of
SNPs with patients' survival. The rs6976500 G allele (CG/GG) genotypes were found
significantly associated with both worse overall survival (OS) and recurrence
free survival (RFS) in the training and the independent validation set when
compared to C allele genotype, which reaching a more robust statistical
significance in the pooled analysis. Furthermore, integration of rs6976500
genotypes and TNM stage significantly improved the prognosis prediction models
based on TNM stage alone. In addition, only carriers with at least one G allele
of rs6976500 gained significant survival benefit from FOLFOX-based ACT.
Mechanistically, SNP rs6976500 G allele genotype could significantly decrease
promoter transcriptional activity and markedly reduce expression level of SSBP1
compared with the C allele genotype in GC cells. This was further substantiated
by immunohistochemical assay in 70 GC tissue samples. Our study presents the
first evidence that SNP rs6976500 G allele genotypes might contribute to GC
prognosis by attenuating SSBP1 promoter activity and gene expression, and
provides the guidance in refining therapeutic decisions of GC patients. Further
exploration on its function is needed to clarify the exact biological mechanism
behind.
PMID- 29340023
TI - Role and regulation of Yap in KrasG12D-induced lung cancer.
AB - The Hippo pathway and its downstream transcriptional co-activator Yap influence
lung cancer, but the nature of the Yap contribution has been unclear. Using a
genetically engineered mouse lung cancer model, we show that Yap deletion
completely blocks KrasG12D and p53 loss-driven adenocarcinoma initiation and
progression, whereas heterozygosity for Yap partially suppresses lung cancer
growth and progression. We also characterize Yap expression during tumor
progression and find that nuclear Yap can be detected from the earliest stages of
lung carcinogenesis, but at levels comparable to that in aveolar type II cells,
which are a cell of origin for lung adenocarcinoma. At later stages of
tumorigenesis, variations in Yap levels are detected, which correlate with
differences in cell proliferation within tumors. Our observations imply that Yap
is not directly activated by oncogenic Kras during lung tumorigenesis, but is
nonetheless absolutely required for this tumorigenesis, and support Yap as a
therapeutic target in lung adenocarcinoma.
PMID- 29340021
TI - A novel messenger RNA signature as a prognostic biomarker for predicting relapse
in pancreatic ductal adenocarcinoma.
AB - Pancreatic ductal adenocarcinoma (PDAC) death rate and recurrence rate have
remained obstinately high. Current methods can not satisfy the need of predicting
cancer relapse accurately. Utilizing expression profiles of 10 GEO datasets (N =
774), we identified 154 differentially expressed genes (DEGs) between PDAC and
normal pancreas tissue or paracancerous tissue. Next we built a 16-mRNA-based
signature by means of the LASSO COX regression model. We also validated the
prognostic value of the signature. Patients were classified into high-risk and
low-risk group according to the signature risk score; 1 year RFS was 45% (95% CI:
31.6%-63.9%) for high-risk group in contrast to 92.5% (95% CI: 86.3%-99.1%) for
low-risk group. Moreover, it could predict RFS well in cases with the receipt of
different treatment modalities. The 16-mRNA-based signature was an independent
and powerful prognostic biomarker for RFS for PDAC patients (HR = 7.74, 95% CI:
3.25-18.45, p < 0.0001).
PMID- 29340024
TI - Chitosan composite scaffold combined with bone marrow-derived mesenchymal stem
cells for bone regeneration: in vitro and in vivo evaluation.
AB - The study aimed to develop a chitosan (CS)-based scaffold for repairing calvarial
bone defects. We fabricated composite scaffolds made of CS and bovine-derived
xenograft (BDX), characterized their physicochemical properties including pore
size and porosity, absorption, degradation, and compressive strength, compared
their efficacy to support in vitro proliferation and differentiation of human jaw
bone marrow-derived mesenchymal stem cells (hJBMMSCs), and evaluated their bone
regeneration capacity in critical-size rat calvarial defects. The CS/BDX (mass
ratio of 40:60) composite scaffold with porosity of 46.23% and pore size of 98.23
MUm exhibited significantly enhanced compressive strength than the CS scaffold
(59.33 +/- 4.29 vs. 18.82 +/- 2.49 Kpa). The CS/BDX (40:60) scaffold induced
better cell attachment and promoted more osteogenic differentiation of hJBMMSCs
than the CS scaffold. The CS/BDX (40:60) scaffold seeded with hJBMMSCs was the
most effective in supporting new bone formation, as evidenced by better
histomorphometry results, larger new bone area, and more obvious mature lamellar
bone formation compared to other groups in rat calvarial defects 8 weeks after
implantation. These results suggest that CS/BDX composite scaffold combining with
hJBMMSCs has the potential for bone defect regeneration.
PMID- 29340025
TI - The novel ATM inhibitor (AZ31) enhances antitumor activity in patient derived
xenografts that are resistant to irinotecan monotherapy.
AB - Irinotecan, a standard of care therapy for CRC, elicits cytotoxic effects by
generating double strand breaks resulting in DNA damage. The activation of the
ATM pathway plays a fundamental role in regulating the cellular response and
repair to DNA damage. The objective of this preclinical study was to determine
whether ATM inhibition would enhance sensitivity to irinotecan treatment.
Treatment effects of AZ31, irinotecan or AZ31 + irinotecan were investigated in
CRC cell lines and CRC patient derived xenografts. Activation of ATM and
downstream targets p-RAD50 and p-H2AX were evaluated by immunohistochemistry.
Combinational effects were demonstrated in 4 out of 8 CRC explants.
Interestingly, each of the combinational sensitive CRC PDX models were shown to
be more resistant to irinotecan single agent therapy. Treatment with irinotecan
significantly elevated the ATM pathway evident by an increase in the activation
of H2AX and RAD50. Combinational therapy reduced the activation of H2AX and RAD50
when compared to irinotecan alone in the combination sensitive CRC098. AZ31 +
irinotecan was effective at reducing tumor growth in tumors that exhibited
resistance to irinotecan in our CRC PDX model. These findings support further
investigation of this combinational therapy for the treatment of CRC patients.
PMID- 29340026
TI - Evaluating the bias of circRNA predictions from total RNA-Seq data.
AB - CircRNAs are a group of endogenous noncoding RNAs. The quickly developing high
throughput RNA sequencing technologies along with novel bioinformatics approaches
have enabled researchers to systematically identify circRNAs and their biological
functions in cells. Deep sequencing of rRNA-depleted RNAs treated with RNase R,
which digests linear RNAs and leaves circRNAs enriched, is an efficient way to
identify circRNAs. However, very few of RNase R treated data are at hand but a
large amount of total RNA-Seq data with no sequencing costs is available, for
circRNA predictions. In this study, we systematically investigated the prediction
bias from total RNA-Seq data as well as the influence of sequencing depth,
sequencing quality and single-end or paired-end sequencing strategy on the
predictions. We also identified circRNA properties that may contribute to the
improved prediction performance. Our analysis shows that circRNA predictions from
total RNA-Seq data gain ~50% true positive. Sequencing error dramatically worsens
the predictions, rather than single-end sequencing strategy or low sequencing
depth. However, false positive can be carefully controlled by using data with
good quality and narrowing down circRNAs guided by their properties.
PMID- 29340027
TI - Dual SIRT1 expression patterns strongly suggests its bivalent role in human
breast cancer.
AB - Breast cancer is the most common cancer in women, and the leading cause of cancer
death in women worldwide. SIRT1 (silent mating type information regulation 2
homolog) 1 is a class-III histone deacetylase involved in apoptosis regulation,
DNA repair and tumorigenesis. However, its role in breast carcinoma remains
controversial, as both tumor-suppressive and tumor-promoting functions have been
reported. Also, there are very few reports available where expression of SIRT1 is
comprehensively analyzed in breast tumors classified by molecular subtype. Here,
using a cohort of 50 human breast tumors and their matched normal tissues, we
investigated SIRT1 expression levels in the 5 molecular subtypes of breast cancer
according to the St Gallen classification (2013). Tumors and their corresponding
normal tissue samples were collected from all patients, and SIRT1 mRNA and
protein expression levels were then examined by real-time quantitative polymerase
chain reaction and immunoblotting, respectively. After statistical analysis, the
results showed a dual expression profile of SIRT1 in human breast carcinoma, with
significant overexpression in luminal and HER2-enriched subtypes and
significantly reduced expression in the triple-negative subtype. We also found an
inverse correlation between SIRT1 expression and breast cancer aggressivity.
These novel findings suggest that SIRT1 plays a dual role in breast tumors
depending on its expression rate and the molecular subtype of the cancer. Our
data also point to a potential role for SIRT1 as a prognostic biomarker in breast
cancer.
PMID- 29340029
TI - Selenium suppresses inflammation by inducing microRNA-146a in Staphylococcus
aureus-infected mouse mastitis model.
AB - We studied the effects of selenium (Se) on the inflammatory response in
Staphylococcus aureus (S. aureus)-infected mastitis-model mice and mammary
epithelial cells. In infected mice, Se elicited a dose-dependent decrease in
mammary gland pathology that included inflammatory cell infiltration,
disorganized acinar structure and mammary cell necrosis. Se decreased
inflammation by increasing miR-146a and decreasing TLR2/6 as well as NF-kappaB
and MAPK signaling pathways in mammary tissue from infected mice and mammary
epithelial cells. A miR-146a inhibitor suppressed the anti-inflammatory effects
of Se in infected mammary epithelial cells. Se, miR-146a and TLR2 were associated
in determining the inflammatory response in mouse with infection-induced
mastitis. Thus, Se inhibits pro-inflammatory responses in mammary tissues from S.
aureus-infected mice by inducing miR-146a.
PMID- 29340028
TI - High-resolution microbiome profiling uncovers Fusobacterium nucleatum,
Lactobacillus gasseri/johnsonii, and Lactobacillus vaginalis associated to oral
and oropharyngeal cancer in saliva from HPV positive and HPV negative patients
treated with surgery and chemo-radiation.
AB - Microbiome studies show altered microbiota in head and neck squamous cell
carcinoma (HNSCC), both in terms of taxonomic composition and metabolic capacity.
These studies utilized a traditional bioinformatics methodology, which allows for
accurate taxonomic assignment down to the genus level, but cannot accurately
resolve species level membership. We applied Resphera Insight, a high-resolution
methodology for 16S rRNA taxonomic assignment that is able to provide species
level context in its assignments of 16S rRNA next generation sequencing (NGS)
data. Resphera Insight applied to saliva samples from HNSCC patients and healthy
controls led to the discovery that a subset of HNSCC saliva samples is
significantly enriched with commensal species from the vaginal flora, including
Lactobacillus gasseri/johnsonii (710x higher in saliva) and Lactobacillus
vaginalis (52x higher in saliva). These species were not observed in normal
saliva from Johns Hopkins patients, nor in 16S rRNA NGS saliva samples from the
Human Microbiome Project (HMP). Interestingly, both species were only observed in
saliva from Human Papilloma Virus (HPV) positive and HPV negative oropharyngeal
cancer patients. We confirmed the representation of both species in HMP data
obtained from mid-vagina (n=128) and vaginal introitus (n=121) samples. Resphera
Insight also led to the discovery that Fusobacterium nucleatum, an oral cavity
flora commensal bacterium linked to colon cancer, is enriched (600x higher) in
saliva from a subset of HNSCC patients with advanced tumors stages. Together,
these high-resolution analyses on 583 samples suggest a possible role for
bacterial species in the therapeutic outcome of HPV positive and HPV negative
HNSCC patients.
PMID- 29340031
TI - Analyzing the influence of kinase inhibitors on DNA repair by differential
proteomics of chromatin-interacting proteins and nuclear phospho-proteins.
AB - The combination of radiotherapy and pharmacological inhibition of cellular signal
transduction pathways offers promising strategies for enhanced cancer cell
inactivation. However, the molecular effects of kinase inhibitors especially on
DNA damage detection and repair after X-irradiation have to be understood to
facilitate the development of efficient and personalized treatment regimens.
Therefore, we applied differential proteomics for analyzing inhibitor-induced
changes in either chromatin-bound or phosphorylated nuclear proteins. The effect
of the multi kinase inhibitor sorafenib on DNA repair, chromatin binding and
phosphorylation of nuclear proteins was analyzed in UT-SCC 42B head and neck
cancer cells using metabolic labeling based differential proteomics (SILAC).
Sorafenib significantly inhibited DNA repair but failed to significantly affect
chromatin interactions of 90 quantified proteins. In contrast, analyzing nuclear
phospho-proteins following sorafenib treatment, we detected quantitative changes
in 9 out of 59 proteins, including DNA-repair proteins. In conclusion, the
analysis of nuclear phospho-proteins by differential proteomics is an effective
tool for determining the molecular effects of kinase inhibitors on X-irradiated
cells. Analyzing chromatin binding might be less promising.
PMID- 29340030
TI - Increased efficacy of metformin corresponds to differential metabolic effects in
the ovarian tumors from obese versus lean mice.
AB - Obesity is a significant risk factor for ovarian cancer (OC) and associated with
worse outcomes for this disease. We assessed the anti-tumorigenic effects of
metformin in human OC cell lines and a genetically engineered mouse model of high
grade serous OC under obese and lean conditions. Metformin potently inhibited
growth in a dose-dependent manner in all four human OC cell lines through
AMPK/mTOR pathways. Treatment with metformin resulted in G1 arrest, induction of
apoptosis, reduction of invasion and decreased hTERT expression. In the K18
gT121+/-; p53fl/fl; Brca1fl/fl (KpB) mouse model, metformin inhibited tumor
growth in both lean and obese mice. However, in the obese mice, metformin
decreased tumor growth by 60%, whereas tumor growth was only decreased by 32% in
the lean mice (p=0.003) compared to vehicle-treated mice. The ovarian tumors from
obese mice had evidence of impaired mitochondrial complex 2 function and energy
supplied by omega fatty acid oxidation rather than glycolysis as compared to lean
mice, as assessed by metabolomic profiling. The improved efficacy of metformin in
obesity corresponded with inhibition of mitochondrial complex 1 and fatty acid
oxidation, and stimulation of glycolysis in only the OCs of obese versus lean
mice. In conclusion, metformin had anti-tumorigenic effects in OC cell lines and
the KpB OC pre-clinical mouse model, with increased efficacy in obese versus lean
mice. Detected metabolic changes may underlie why ovarian tumors in obese mice
have heightened susceptibility to metformin.
PMID- 29340032
TI - C3G promotes a selective release of angiogenic factors from activated mouse
platelets to regulate angiogenesis and tumor metastasis.
AB - Previous observations indicated that C3G (RAPGEF1) promotes alpha-granule
release, evidenced by the increase in P-selectin exposure on the platelet surface
following its activation. The goal of the present study is to further
characterize the potential function of C3G as a modulator of the platelet
releasate and its implication in the regulation of angiogenesis. Proteomic
analysis revealed a decreased secretion of anti-angiogenic factors from activated
transgenic C3G and C3G?Cat platelets. Accordingly, the secretome from both
transgenic platelets had an overall pro-angiogenic effect as evidenced by an in
vitro capillary-tube formation assay with HUVECs (human umbilical vein
endothelial cells) and by two in vivo models of heterotopic tumor growth. In
addition, transgenic C3G expression in platelets greatly increased mouse melanoma
cells metastasis. Moreover, immunofluorescence microscopy showed that the pro
angiogenic factors VEGF and bFGF were partially retained into alpha-granules in
thrombin- and ADP-activated mouse platelets from both, C3G and C3GDeltaCat
transgenic mice. The observed interaction between C3G and Vesicle-associated
membrane protein (Vamp)-7 could explain these results. Concomitantly, increased
platelet spreading in both transgenic platelets upon thrombin activation supports
this novel function of C3G in alpha-granule exocytosis. Collectively, our data
point out to the co-existence of Rap1GEF-dependent and independent mechanisms
mediating C3G effects on platelet secretion, which regulates pathological
angiogenesis in tumors and other contexts. The results herein support an
important role for platelet C3G in angiogenesis and metastasis.
PMID- 29340033
TI - CXCR4-expressing Mist1+ progenitors in the gastric antrum contribute to gastric
cancer development.
AB - Mist1 was recently shown to identify a discrete population of stem cells within
the isthmus of the oxyntic gland within the gastric corpus. Chief cells at the
base of the gastric corpus also express Mist1. The relevance of Mist1 expression
as a marker of specific cell populations within the antral glands of the distal
stomach, however, is unknown. Using Mist1-CreERT mice, we revealed that Mist1+
antral cells, distinct from the Mist1+ population in the corpus, comprise long
lived progenitors that reside within the antral isthmus above Lgr5+ or CCK2R+
cells. Mist1+ antral progenitors can serve as an origin of antral tumors induced
by loss of Apc or MNU treatment. Mist1+ antral progenitors, as well as other
antral stem/progenitor population, express Cxcr4, and are located in close
proximity to Cxcl12 (the Cxcr4 ligand)-expressing endothelium. During antral
carcinogenesis, there is an expansion of Cxcr4+ epithelial cells as well as the
Cxcl12+ perivascular niche. Deletion of Cxcl12 in endothelial cells or
pharmacological blockade of Cxcr4 inhibits antral tumor growth. Cxcl12/Cxcr4
signaling may be a potential therapeutic target.
PMID- 29340034
TI - Prexasertib, a cell cycle checkpoint kinases 1 and 2 inhibitor, increases in
vitro toxicity of PARP inhibition by preventing Rad51 foci formation in BRCA wild
type high-grade serous ovarian cancer.
AB - PARP inhibitors (PARPi) have been effective in high-grade serous ovarian cancer
(HGSOC), although clinical activity is limited against BRCA wild type HGSOC. The
nearly universal loss of normal p53 regulation in HGSOCs causes dysfunction in
the G1/S checkpoint, making tumor cells reliant on Chk1-mediated G2/M cell cycle
arrest for DNA repair. Therefore, Chk1 is a reasonable target for a combination
strategy with PARPi in treating BRCA wild type HGSOC. Here we investigated the
combination of prexasertib mesylate monohydrate (LY2606368), a Chk1 and Chk2
inhibitor, and a PARP inhibitor, olaparib, in HGSOC cell lines (OVCAR3, OV90,
PEO1 and PEO4) using clinically attainable concentrations. Our findings showed
combination treatment synergistically decreased cell viability in all cell lines
and induced greater DNA damage and apoptosis than the control and/or
monotherapies (p<0.05). Treatment with olaparib in BRCA wild type HGSOC cells
caused formation of Rad51 foci, whereas the combination treatment with
prexasertib inhibited transnuclear localization of Rad51, a key protein in
homologous recombination repair. Overall, our data provide evidence that
prexasertib and olaparib combination resulted in synergistic cytotoxic effects
against BRCA wild type HGSOC cells through reduced Rad51 foci formation and
greater induction of apoptosis. This may be a novel therapeutic strategy for
HGSOC.
PMID- 29340035
TI - ABCB1 3435TT and ABCG2 421CC genotypes were significantly associated with longer
progression-free survival in Chinese breast cancer patients.
AB - Objective: To investigate the distribution of ABCB1 C3435T and ABCG2 C421A gene
polymorphisms in Chinese Han population and their influences on the
susceptibility and prognosis of breast carcinoma. Methods: A total of 200 female
subjects were enrolled in this study, comprising 100 breast cancer patients and
100 healthy controls. Carcinoma and para-carcinoma tissues were collected from
the breast cancer patients, while peripheral blood was collected from healthy
controls. Single nucleotide polymorphisms (SNPs) were detected by the Taqman
method. Progression-free survival (PFS) and 5-year survival rate of the patients
were calculated. Results: ABCB1 C3435T and ABCG2 C421A polymorphisms were not
associated with disease susceptibility and 5-year survival rate in the study
population (p>0.05). However, a high mutation rate of both ABCB1 C3435T and ABCG2
C421A (16% and 17%, respectively) was observed in breast cancer tissues. Patients
with ABCB1 3435TT genotype or ABCG2 421CC genotype had longer PFS (p<0.05).
Conclusion: ABCB1 3435TT and ABCG2 421CC were significantly associated with
longer PFS in Chinese breast cancer patients.
PMID- 29340036
TI - The association between elevated fasting plasma glucose levels and carotid intima
media thickness in non-diabetic adults: a population-based cross-sectional study.
AB - We assessed the association between the mean carotid intima-media thickness
(CIMT) and fasting plasma glucose (FPG) levels in a low-income population in
rural China. Adults aged >=45 years without a history of diabetes, stroke, or
cardiovascular disease were recruited. All participants were categorized into
four groups according to FPG level. A total of 3509 participants were analyzed in
this study. In the univariate analysis, sex, age, education level, hypertension,
central obesity, current smoking, alcohol consumption, and higher levels of FPG,
total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol
(HDL-C), and low-density lipoprotein cholesterol (LDL-C) were associated with
mean CIMT and frequency of increased CIMT. FPG levels were significantly
associated with mean CIMT; each 1-mmol/L increase in FPG resulted in a 2.75-MUm
increase in mean CIMT when adjusted by age, sex, education level, current smoking
status, alcohol consumption, hypertension, and the levels of TC, TG, HDL-C, and
LDL-C (P = 0.044). However, the association between FPG and the frequency of
increased CIMT disappeared after adjusting by covariates. These findings indicate
that FPG is an independent determinant of mean CIMT in a non-diabetic population.
Management and control of FPG levels is crucial for preventing atherosclerosis in
populations with high stroke risks in China.
PMID- 29340037
TI - Systemic bioinformatics analysis of recurrent aphthous stomatitis gene expression
profiles.
AB - Recurrent aphthous stomatitis (RAS) represents the most common chronic oral
diseases with the prevalence ranges from 5% to 25% for different populations. Its
pathogenesis remains poorly understood, which limits the development of effective
drugs and treatment methods. In this study, we conducted systemic bioinformatics
analysis of gene expression profiles from the Gene Expression Omnibus (GEO) to
identify potential drug targets for RAS. We firstly downloaded the gene
microarray datasets with the accession number of GSE37265 from GEO and performed
robust multi-array (RMA) normalization with affy R programming package. Secondly,
differential expression genes (DEGs) in RAS samples compared with control samples
were identified based on limma package. Enriched gene ontology (GO) terms and
Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of DEGs were obtained
through the Database for Annotation, Visualization and Integrated Discovery
(DAVID). Finally, protein-protein interaction (PPI) network was constructed based
on the combination of HPRD and BioGrid databases. What's more, we identified
modules of PPI network through MCODE plugin of Cytoscape for the purpose of
screening of valuable targets. As a result, 915 genes were found to be
significantly differential expression in RAS samples and biological processes
related to immune and inflammatory response were significantly enriched in those
genes. Network and module analysis identified FBXO6, ITGA4, VCAM1 and etc as
valuable therapeutic targets for RAS. Finally, FBXO6, ITGA4, and VCAM1 were
further confirmed by real time RT-PCR and western blot. This study should be
helpful for the research and treatment of RAS.
PMID- 29340038
TI - Diagnostic performance of 68Gallium-PSMA-11 PET/CT to detect significant prostate
cancer and comparison with 18FEC PET/CT.
AB - Background: Radiolabeled prostate-specific membrane antigen (PSMA) has proven to
be a highly accurate method to detect recurrence and metastases of prostate
cancer, but only sparse data is available about its performance in the diagnosis
of clinically significant primary prostate cancer. Methods: We compared 68Ga-PSMA
11 PET/CT in 25 patients with 18FEC PET/CT in 40 patients with suspected prostate
carcinoma based on an increased PSA level.The PET/CT results were compared with
the histopathologic Gleason Score (GS) of biopsies. Results: The 68Ga-PSMA-11
PET/CT revealed highly suspect prostatic lesions (maximum standardized uptake
value/SUVmax >2.5) in 21/25 patients (84%), associated with GS>=6 (low-grade/high
grade carcinoma). Two histopathologic non-malignancy-relevant cases (GS<6) had
PSMA-SUVmax <=2.5; all histopathologic high-grade cases (GS>=7b) showed PSMA
SUVmax >12.0 which further increased with rising GS. There were 2 false positives
and no false negative findings for high-grade prostate cancer using a cut off
level for SUVmax of 2.5.In contrast, the 18FEC PET/CT showed suspected malignant
lesions in 38/40 patients (95%), which included 3 lesions with GS<6. The mean
SUVmax values did not differ with different GS. There were 11 false positives and
1 false negative for detection of high-grade prostate cancer (cut off 2.5).By
means of ROC analysis a SUVmax of 5.4 was found to be an optimal cut off-level to
distinguish between low- and high-grade carcinoma in 68Ga-PSMA-11 PET/CT
(AUC=0.9692; 95% CI 0.9086;1.0000;SD(AUC)=0.0309)). Choosing a cut off-level of
SUVmax5.4, 68Ga-PSMA-11 PET/CT was able to distinguish between GS <=7a/>=7b with
a sensitivity of 84%, a specificity of 100%, a negative predictive value (NPV) of
67%, and an efficiency of 88% (p<0.001).The ROC analysis revealed a SUVmax 6.5 as
an optimal cut off-level to distinguish between low- and high-grade carcinoma in
18FEC PET/CT (AUC=0.7470; 95% CI 0.5919;0.9020;SD(AUC)=0.0791) with a sensitivity
of 61% and a specificity of 92%; but the efficiency was only 70% and the NPV 50%
(p=0.01). Conclusion: 68Ga-PSMA-11 PET/CT guided biopsy of the prostate increases
diagnostic precision and is likely to help to reduce overtreatment of low-grade
malignant disease as well as detect the foci of the highest Gleason pattern. Both
methods (68Ga-PSMA-11,18FEC) were suitable to detect primary prostate cancer, but
the excellent image quality, the higher specificity and the good correlation of
positive scans with GS are advantages of 68Ga-PSMA-11.
PMID- 29340039
TI - Integrative molecular network analysis identifies emergent enzalutamide
resistance mechanisms in prostate cancer.
AB - Recent work demonstrates that castration-resistant prostate cancer (CRPC) tumors
harbor countless genomic aberrations that control many hallmarks of cancer. While
some specific mutations in CRPC may be actionable, many others are not. We
hypothesized that genomic aberrations in cancer may operate in concert to promote
drug resistance and tumor progression, and that organization of these genomic
aberrations into therapeutically targetable pathways may improve our ability to
treat CRPC. To identify the molecular underpinnings of enzalutamide-resistant
CRPC, we performed transcriptional and copy number profiling studies using paired
enzalutamide-sensitive and resistant LNCaP prostate cancer cell lines. Gene
networks associated with enzalutamide resistance were revealed by performing an
integrative genomic analysis with the PAthway Representation and Analysis by
Direct Reference on Graphical Models (PARADIGM) tool. Amongst the pathways
enriched in the enzalutamide-resistant cells were those associated with MEK,
EGFR, RAS, and NFKB. Functional validation studies of 64 genes identified 10
candidate genes whose suppression led to greater effects on cell viability in
enzalutamide-resistant cells as compared to sensitive parental cells. Examination
of a patient cohort demonstrated that several of our functionally-validated gene
hits are deregulated in metastatic CRPC tumor samples, suggesting that they may
be clinically relevant therapeutic targets for patients with enzalutamide
resistant CRPC. Altogether, our approach demonstrates the potential of
integrative genomic analyses to clarify determinants of drug resistance and
rational co-targeting strategies to overcome resistance.
PMID- 29340040
TI - Identifying the dynamics of actin and tubulin polymerization in iPSCs and in iPSC
derived neurons.
AB - The development of the nervous system requires cytoskeleton-mediated processes
coordinating self-renewal, migration, and differentiation of neurons. It is not
surprising that many neurodevelopmental problems and neurodegenerative disorders
are caused by deficiencies in cytoskeleton-related genes. For this reason, we
focus on the cytoskeletal dynamics in proliferating iPSCs and in iPSC-derived
neurons to better characterize the underpinnings of cytoskeletal organization
looking at actin and tubulin repolymerization studies using the cell permeable
probes SiR-Actin and SiR-Tubulin. During neurogenesis, each neuron extends an
axon in a complex and changing environment to reach its final target. The dynamic
behavior of the growth cone and its capacity to respond to multiple spatial
information allows it to find its correct target. We decided to characterize
various parameters of the actin filaments and microtubules. Our results suggest
that a rapid re-organization of the cytoskeleton occurs 45 minutes after
treatments with de-polymerizing agents in iPSCs and 60 minutes in iPSC-derived
neurons in both actin filaments and microtubules. The quantitative data confirm
that the actin filaments have a primary role in the re-organization of the
cytoskeleton soon after de-polymerization, while microtubules have a major
function following cytoskeletal stabilization. In conclusion, we investigate the
possibility that de-polymerization of the actin filaments may have an impact on
microtubules organization and that de-polymerization of the microtubules may
affect the stability of the actin filaments. Our results suggest that a
reciprocal influence of the actin filaments occurs over the microtubules and vice
versa in both in iPSCs and iPSC-derived neurons.
PMID- 29340041
TI - Discovery of a highly selective KIT kinase primary V559D mutant inhibitor for
gastrointestinal stromal tumors (GISTs).
AB - KIT kinase V559D mutation is the most prevalent primary gain-of-function mutation
in Gastrointestinal Stromal Tumors (GISTs). Here we reported a highly selective
KIT V559D inhibitor CHMFL-KIT-031, which displayed about 10-20 fold selectivity
over KIT wt in the biochemical assay (IC50: 28 nM over 168 nM; Kd: 266 nM versus
6640 nM) and in cell (EC50: 176 nM versus 2000 nM for pY703) examination. It also
displayed 15~400-fold selectivity over other primary mutants such as L576P and
secondary mutants including T670I, V654A (ATP binding pocket) as well as N822K
and D816V (activation loop). In addition, it exhibited a selectivity S score (1)
of 0.01 among 468 kinases/mutants in the KINOMEScanTM assay. CHMFL-KIT-031 showed
potent inhibitory efficacy for KIT V559D mediated signaling pathways in cell and
anti-tumor activity in vivo (Tumor Growth Inhibition: 68.5%). Its superior
selectivity would make it a good pharmacological tool for further dissection of
KIT V559D mediated pathology in the GISTs.
PMID- 29340042
TI - Identification of potential genetic causal variants for rheumatoid arthritis by
whole-exome sequencing.
AB - Rheumatoid arthritis (RA) is a highly prevalent chronic autoimmune disease.
However, genetic and environmental factors involved in RA pathogenesis are still
remained largely unknown. To identify the genetic causal variants underlying
pathogenesis and disease progression of RA patients, we undertook the first
comprehensive whole-exome sequencing (WES) study in a total of 124 subjects
including 58 RA cases and 66 healthy controls in Han Chinese population. We
identified 378 novel genes that were enriched with deleterious variants in RA
patients using a gene burden test. The further functional effects of associated
genetic genes were classified and assessed, including 21 newly identified genes
that were involved in the extracellular matrix (ECM)-receptor interaction,
protein digestion and absorption, focal adhesion and glycerophospholipid
metabolism pathways relevant to RA pathogenesis. Moreover, six pathogenic
variants were investigated and structural analysis predicted their potentially
functional alteration by homology modeling. Importantly, five novel and rare
homozygous variants (NCR3LG1, RAP1GAP, CHCHD5, HIPK2 and DIAPH2) were identified,
which may exhibit more functional impact on RA pathogenesis. Notably, 7 genes
involved in the olfactory transduction pathway were enriched and associated with
RA disease progression. Therefore, we performed an efficient and powerful
technique WES in Chinese RA patients and identified novel, rare and common
disease causing genes that alter innate immunity pathways and contribute to the
risk of RA. Findings in this study may provide potential diagnostic tools and
therapeutic strategies for RA patients.
PMID- 29340043
TI - Clinical significance of YAP1 activation in head and neck squamous cell
carcinoma.
AB - By analyzing the genomic data of head and neck squamous cell cancer (HNSCC), we
investigated clinical significance of YAP1 activation. Copy number and mRNA
expression of YAP1 were analyzed together to assess clinical relevance of YAP1
activation in HNSCC. The clinical significance of YAP1 activation was further
validated in four independent test cohorts. We also assessed the correlation of
YAP1 activation with genomic alterations such as copy number alteration, somatic
mutation, and miRNA expression. The YAP1-activated (YA) subgroup showed worse
prognosis for HNSCC as tested and validated in five cohorts. In a multivariate
risk analysis, the YAP1 signature was the most significant predictor of overall
survival. The YAP1-inactivated (YI) subgroup was associated with HPV-positive
status. In multiplatform analysis, YA tumors had gain of EGFR and SNAI2; loss of
tumor-suppressor genes such as CSMD1, CDKN2A, NOTCH1, and SMAD4; and high
mutation rates of TP53 and CDKN2A. YI tumors were characterized by gain of
PIK3CA, SOX2, and TP63; deletion of 11q23.1; and high mutation rates of NFE2L2,
PTEN, SYNE1, and NSD1. YA tumors also showed weaker immune activity as reflected
in low IFNG composite scores and YAP1 activity is negatively associated with
potential response to treatment of pembrolizumab. In conclusion, activation of
YAP1 is associated with worse prognosis of patients with HNSCC and potential
resistance to immunotherapy.
PMID- 29340045
TI - RIP140 and LCoR expression in gastrointestinal cancers.
AB - The transcription coregulators RIP140 and LCoR are part of a same complex which
controls the activity of various transcription factors and cancer cell
proliferation. In this study, we have investigated the expression of these two
genes in human colorectal and gastric cancers by immunohistochemistry. In both
types of tumors, the levels of RIP140 and LCoR appeared highly correlated. Their
expression tended to decrease in colorectal cancer as compared to adjacent normal
tissues but was found higher in gastric cancer as compared to normal stomach.
RIP140 and LCoR expression correlated with TNM and tumor differentiation.
Significant correlations were observed with expression levels of key proteins
involved in tumor progression and invasion namely E-cadherin and Cyclooxygenase
2. Survival analysis showed that patients with LCoRlow/RIP140high colorectal
tumors have a significant prolonged overall and disease-free survival. In gastric
cancer, high LCoR expression was identified as an independent marker of poor
prognosis suggesting a key role in this malignancy. Altogether, these results
demonstrate that RIP140 and LCoR have a prognostic relevance in gastrointestinal
cancers and could represent new potential biomarkers in these tumors.
PMID- 29340044
TI - Cepharanthine hydrochloride reverses the mdr1 (P-glycoprotein)-mediated
esophageal squamous cell carcinoma cell cisplatin resistance through JNK and p53
signals.
AB - Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy that is
often resistant to therapy. Nowadays, chemotherapy is still one of the main
methods for the treatment of ESCC. However, the multidrug resistance (MDR)
mediated chemotherapy resistance is one of the leading causes of death. Exploring
agents able to reverse MDR, which thereby increase the sensitivity with clinical
first-line chemotherapy drugs, could significantly improve cancer treatment.
Cepharanthine hydrochloride (CEH) has the ability to reverse the MDR in ESCC and
the mechanism involved have not been reported. The aim of the study was to
investigate the potential of CEH to sensitize chemotherapeutic drugs in ESCC and
explore the underlying mechanisms by in vitro and in vivo studies. Our data
demonstrated that CEH significantly inhibited ESCC cell proliferation in a dose
dependent manner, induced G2/M phase cell cycle arrest and apoptosis, and
increased the sensitivity of cell lines resistant to cisplatin (cDDP).
Mechanistically, CEH inhibited ESCC cell growth and induced apoptosis through
activation of c-Jun, thereby inhibiting the expression of P-gp, and enhancing p21
expression via activation of the p53 signaling pathway. In this study, we
observed that growth of xenograft tumors derived from ESCC cell lines in nude
mice was also significantly inhibited by combination therapy. To our knowledge,
we demonstrate for the first time that CEH is a potentially effective MDR
reversal agent for ESCC, based on downregulation of the mRNA expression of MDR1
and P-gp. Together, these results reveal emphasize CEH putative role as a
resistance reversal agent for ESCC.
PMID- 29340046
TI - Sampling from single-cell observations to predict tumor cell growth in-vitro and
in-vivo.
AB - Cancer stem-like cells (CSCs) are a topic of increasing importance in cancer
research, but are difficult to study due to their rarity and ability to rapidly
divide to produce non-self-cells. We developed a simple model to describe
transitions between aldehyde dehydrogenase (ALDH) positive CSCs and ALDH(-) bulk
ovarian cancer cells. Microfluidics device-isolated single cell experiments
demonstrated that ALDH+ cells were more proliferative than ALDH(-) cells. Based
on our model we used ALDH+ and ALDH(-) cell division and proliferation properties
to develop an empiric sampling algorithm and predict growth rate and CSC
proportion for both ovarian cancer cell line and primary ovarian cancer cells, in
vitro and in-vivo. In both cell line and primary ovarian cancer cells, the
algorithm predictions demonstrated a high correlation with observed ovarian
cancer cell proliferation and CSC proportion. High correlation was maintained
even in the presence of the EGF-like domain multiple 6 (EGFL6), a growth factor
which changes ALDH+ cell asymmetric division rates and thereby tumor growth
rates. Thus, based on sampling from the heterogeneity of in-vitro cell growth and
division characteristics of a few hundred single cells, the simple algorithm
described here provides rapid and inexpensive means to generate predictions that
correlate with in-vivo tumor growth.
PMID- 29340047
TI - Inhibition of polo-like kinase 4 (PLK4): a new therapeutic option for rhabdoid
tumors and pediatric medulloblastoma.
AB - Rhabdoid tumors (RT) are highly aggressive and vastly unresponsive embryonal
tumors. They are the most common malignant CNS tumors in infants below 6 months
of age. Medulloblastomas (MB) are embryonal tumors that arise in the cerebellum
and are the most frequent pediatric malignant brain tumors. Despite the advances
in recent years, especially for the most favorable molecular subtypes of MB, the
prognosis of patients with embryonal tumors remains modest with treatment related
toxicity dreadfully high. Therefore, new targeted therapies are needed. The polo
like kinase 4 (PLK4) is a critical regulator of centriole duplication and
consequently, mitotic progression. We previously established that PLK4 is
overexpressed in RT and MB. We also demonstrated that inhibiting PLK4 with a
small molecule inhibitor resulted in impairment of proliferation, survival,
migration and invasion of RT cells. Here, we showed in MB the same effects that
we previously described for RT. We also demonstrated that PLK4 inhibition induced
apoptosis, senescence and polyploidy in RT and MB cells, thereby increasing the
susceptibility of cancer cells to DNA-damaging agents. In order to test the
hypothesis that PLK4 is a CNS druggable target, we demonstrated efficacy with
oral administration to an orthotropic xenograft model. Based on these results, we
postulate that targeting PLK4 with small-molecule inhibitors could be a novel
strategy for the treatment of RT and MB and that PLK4 inhibitors (PLK4i) might be
promising agents to be used solo or in combination with cytotoxic agents.
PMID- 29340048
TI - Alteration of mitochondrial biogenesis promotes disease progression in multiple
myeloma.
AB - Many cancers, including multiple myeloma (MM), retain more cytosolic iron to
promote tumor cell growth and drug resistance. Higher cytosolic iron promotes
oxidative damage due to its interaction with reactive oxygen species generated by
mitochondria. The variation of mitochondrial biogenesis in different stages of MM
disease was evaluated using gene expression profiles in a large clinical dataset.
Sixteen of 18mitochondrial biogenesis related gene sets, including mitochondrial
biogenesis signature and oxidative phosphorylation, were increased in myeloma
cells compared with normal plasma cells and high expression was associated with
an inferior patient outcome. Relapsed and drug resistant myeloma samples had
higher expression of mitochondrial biogenesis signatures than newly diagnosed
patient samples. The expression of mitochondrial biogenesis genes was regulated
by the cellular iron content, which showed a synergistic effect in patient
outcome in MM. Pharmacological ascorbic acid induced myeloma cell death by
inhibition of mitochondria oxidative phosphorylation in an in vivo model. Here,
we identify that dysregulated mitochondrial biogenesis and iron homeostasis play
a major role in myeloma progression and patient outcome and that pharmacological
ascorbic acid, through cellular iron content and mitochondrial oxidative species,
should be considered as a novel treatment in myeloma including drug-resistant and
relapsed patients.
PMID- 29340050
TI - Molecular characteristics and clinical outcomes of EGFR exon 19 indel subtypes to
EGFR TKIs in NSCLC patients.
AB - Patients with non-small cell lung cancer (NSCLC) with activating epidermal growth
factor receptor (EGFR) mutations (exon 19 deletions and L858R) benefit from EGFR
tyrosine kinase inhibitors (TKIs). However, some researchers have reported that
responses to TKIs differ by subtypes of EGFR exon 19 mutations. We
retrospectively analyzed EGFR exon 19 deletion subtypes and their correlation
with clinical outcomes of treatment with TKIs. A cohort of 2664 consecutive
patients with NSCLC was enrolled. A total of 440 EGFR exon 19 deletions were
defined as 39 subtypes. Among them, 158 patients with advanced lung
adenocarcinoma with EGFR exon 19 deletion mutations received EGFR-TKIs. There
were no significant differences in progression-free survival or overall survival
among patients with non-LRE deletions, delE746, or delL747 (P = 0.463 and P =
0.464, respectively). Furthermore, two patients with EGFR exon19 insertion had
durable response to EGFR-TKIs. In conclusion, EGFR exon 19 is highly fragile,
resulting in many different deletion and insertion subtypes. There were no
significant differences in clinical outcomes after TKI treatment across the
different subtypes. It is necessary to attempt to identify all patients with exon
19 deletions so that they can be offered TKI treatment.
PMID- 29340049
TI - Pharmacological treatment with inhibitors of nuclear export enhances the
antitumor activity of docetaxel in human prostate cancer.
AB - Background and aims: Docetaxel (DTX) modestly increases patient survival of
metastatic castration-resistant prostate cancer (mCRPC) due to insurgence of
pharmacological resistance. Deregulation of Chromosome Region Maintenance (CRM
1)/ exportin-1 (XPO-1)-mediated nuclear export may play a crucial role in this
phenomenon. Material and methods: Here, we evaluated the effects of two Selective
Inhibitor of Nuclear Export (SINE) compounds, selinexor (KPT-330) and KPT-251, in
association with DTX by using 22rv1, PC3 and DU145 cell lines with their. DTX
resistant derivatives. Results and conclusions: We show that DTX resistance may
involve overexpression of beta-III tubulin (TUBB3) and P-glycoprotein as well as
increased cytoplasmic accumulation of Foxo3a. Increased levels of XPO-1 were also
observed in DTX resistant cells suggesting that SINE compounds may modulate DTX
effectiveness in sensitive cells as well as restore the sensitivity to DTX in
resistant ones. Pretreatment with SINE compounds, indeed, sensitized to DTX
through increased tumor shrinkage and apoptosis by preventing DTX-induced cell
cycle arrest. Basally SINE compounds induce FOXO3a activation and nuclear
accumulation increasing the expression of FOXO-responsive genes including p21,
p27 and Bim causing cell cycle arrest. SINE compounds-catenin and survivin
supporting apoptosis. betadown-regulated Cyclin D1, c-myc, Nuclear sequestration
of p-Foxo3a was able to reduce ABCB1 and TUBB3 H2AX levels, prolonged gamma
expression. Selinexor treatment increased DTX-mediated double strand breaks
(DSB), and reduced the levels of DNA repairing proteins including DNA PKc and
Topo2A. Our results provide supportive evidence for the therapeutic use of SINE
compounds in combination with DTX suggesting their clinical use in mCRPC
patients.
PMID- 29340051
TI - MicroRNA-34a inhibits cells proliferation and invasion by downregulating Notch1
in endometrial cancer.
AB - MicroRNAs (miRNAs) are small non-coding RNAs composed of 18-25 nucleotides that
regulate the expression of approximately 30% of human protein coding genes.
Dysregulation of miRNAs plays a pivotal role in the initiation and progression of
malignancies. Our study has shown that microRNA-34a (miR-34a) was upregulated in
human endometrial cancer stem cells (ECSCs). However, it is unknown how miR-34a
regulates endometrial cancer itself. Here, we report that miR-34a directly and
functionally targeted Notch1. MiR-34a inhibited the proliferation, migration,
invasion, EMT-associated phenotypes by downregulating Notch1 in endometrial
cancer cells. Overexpression of miR-34a also suppressed tumor growth in nude
mice. Importantly, further results suggested miR-34a was significantly
downregulated in endometrial cancer tissues and negatively correlated with Notch1
expression. There was a significant association between decreased miR-34a
expression and worse patient prognosis. Taken together, our results suggest that
miR-34a plays tumor-suppressive roles in endometrial cancer through
downregulating Notch1. Thus miR-34a could be a potential therapeutic target for
prevention and treatment of endometrial cancer.
PMID- 29340052
TI - Gene expression profiling and construction of a putative gene regulatory network
of bladder cancer tumor-initiating cells.
AB - Human bladder cancer tumors have been shown to contain a subpopulation of cells
with stem-like characteristics that may trigger tumor growth, recurrence, and
metastasis. These cells, known as tumor-initiating cells (TICs), would be
effective diagnostic tools and valuable therapeutic targets. Here, we report the
isolation of TICs from seven bladder cancer cell lines and show that TICs from
different sources vary on their ability to form tumorspheres in vitro and
generate xenografts in vivo, which suggest they are remarkably heterogeneous. We
used the Affymetrix PrimeViewTM Human Gene Expression Array to analyze gene
expression profiles of bladder TICs, which may help understand their tumorigenic
capacities and develop novel treatments specifically targeted toward these cells.
We then constructed a transcription factor-gene regulatory network that includes
three key transcription factors that are involved in cell survival,
differentiation, proliferation, and apoptosis. We validated our findings by
analyzing mRNA expression of the key genes in this network in 24 clinical
tissues. Our results suggest that this transcription factor-gene regulatory
network could be useful in the development of clinical diagnostic tools and
therapy approaches for bladder cancer.
PMID- 29340053
TI - Indomethacin-based stimuli-responsive micelles combined with paclitaxel to
overcome multidrug resistance.
AB - Development of multidrug resistance against antitumor agents is a major limiting
factor for the successful chemotherapy. Currently, both amphiphilic polymeric
micelles and chemosensitizers have been proposed to overcome MDR during
chemotherapy. Herein, the redox-responsive polymeric micelles composed of dextran
and indomethacin (as chemosensitizer) using a disulfide bond as the linker are
prepared (DEX-SS-IND) for delivery of antitumor agent paclitaxel (PTX). The high
level of glutathione in tumor cells selectively breaks the disulfide bond,
leading to the rapid breakdown and deformation of redox-responsive polymeric
micelles. The data show that DEX-SS-IND can spontaneously form the stable
micelles with high loading content (9.48 +/- 0.41%), a favorable size of 45 nm
with a narrow polydispersity (0.157), good stability, and glutathione-triggered
drug release behavior due to the rapid breakdown of disulfide bond between DEX
and IND. In vitro antitumor assay shows DEX-SS-IND/PTX micelles effectively
inhibit the proliferation of PTX-resistant breast cancer (MCF-7/PTX) cells. More
impressively, DEX-SS-IND/PTX micelles possess the improved plasma
pharmacokinetics, enhanced antitumor efficacy on tumor growth in the xenograft
models of MCF-7/PTX cells, and better in vivo safety. Overall, DEX-SS-IND/PTX
micelles display a great potential for cancer treatment, especially for multidrug
resistance tumors.
PMID- 29340054
TI - Febuxostat attenuates ER stress mediated kidney injury in a rat model of
hyperuricemic nephropathy.
AB - Hyperuricemia contributes to kidney tubular injury and kidney fibrosis. However,
the underlying mechanism remains unclear. Here we examined the role of RTN1A, a
novel endoplasmic reticulum (ER)-associated protein and ER stress in
hyperuricemic nephropathy. We first found the expression of RTN1A and ER stress
markers was significantly increased in kidney biopsies of hyperuricemia patients
with kidney injury. In a rat model of hyperuricemic nephropathy (HN) established
by oral administration of a mixture of adenine and potassium oxonate, increased
expression of RTN1A and ER stress was shown in tubular and interstitial
compartment of rat kidneys. Treatment of Febuxostat, a new selective inhibitor of
xanthine oxidase (XO), not only attenuated renal tubular injury and
tubulointerstitial fibrosis, but also reduced uric acid crystals deposition in HN
rat kidneys. In vitro, Febuxostat also reduced ER stress and apoptosis in uric
acid treated tubular epithelial cells. Our data suggest that RTN1A and ER stress
mediate tubular cell injury and kidney fibrosis in HN. Urate-lowering therapy
(ULT) with Febuxostat attenuates uric-acid induced ER stress in renal tubular
cells and the progression of HN.
PMID- 29340055
TI - Concurrent brain radiotherapy and EGFR-TKI may improve intracranial metastases
control in non-small cell lung cancer and have survival benefit in patients with
low DS-GPA score.
AB - Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) has
intracranial activity in EGFR-mutant Non-Small Cell Lung Cancer (NSCLC). The
optimal timing of brain radiotherapy (RT) and appropriate patients who need early
brain RT remains undetermined. This is a retrospective study of EGFR-mutant NSCLC
patients with newly diagnosed brain metastases (BMs) before EGFR-TKI initiation.
Intra-cranial progression free survival (IC-PFS) and overall survival (OS) were
measured from the date of EGFR-TKI treatment. A total of 113 patients were
eligible, 49 received concurrent early brain RT with EGFR-TKI and 64 were treated
with EGFR-TKI alone as initial therapy, including 27 with salvage RT upon BM
progression. The patients with early brain RT had superior IC-PFS than those
without early brain RT (21.4 vs 15.0 months, P=0.001), which remained significant
in multivariate analysis (HR 0.30, P<0.001). The median overall survival (OS) for
early RT, EGFR-TKI alone and salvage RT groups was 28.1, 24.5, and 24.6 months,
respectively (P=0.604). Similar IC-PFS (23.6 vs 21.4 months, P=0.253) and OS
(24.6 vs 28.1 months, P=0.385) were observed between salvage RT and early RT
groups. For patients with Diagnosis-Specific Graded Prognostic Assessment (DS
GPA) score of 0 to 2, early brain RT was the independent factor for improved OS
(HR 0.33, P=0.025). In conclusion, concurrent early brain RT with EGFR-TKI may
improve intracranial disease control in EGFR-mutant NSCLC with BM and have
survival benefit in patients with low DS-GPA score. Salvage brain RT upon BM
progression may be acceptable in some patients.
PMID- 29340056
TI - Temozolomide encapsulated and folic acid decorated chitosan nanoparticles for
lung tumor targeting: improving therapeutic efficacy both in vitro and in vivo.
AB - Folic acid-conjugated temozolomide (TMZ)-loaded chitosan nanoparticles (CS-TMZ
FLA-NP) were developed to target lung cancer in the anticipation that folic acid
would increase the affinity of nanoparticles for cancer cells. CS-TMZ-FLA-NP
showed the highest anti-proliferative effect on the lung cancer cells in
comparison to free TMZ and CS-TMZ-NP (nanoparticles without folic acid). A
cellular uptake assay was performed on two different cell lines, L132 and A549.
Cellular uptake efficiencies of CS-TMZ-NP and CS-TMZ-FLA-NP were found to be
concentration-dependent in both cell lines. CS-TMZ-FLA-NP produced a 2.5 fold
greater accumulation of TMZ than CS-TMZ-NP in both cell lines. CS-TMZ-FLA-NP
maintained a significantly higher deposition of TMZ in lung tissue (approximately
7.5 MUg/g of lung tissue) when compared to free TMZ and CS-TMZ-NP. Mice treated
with CS-TMZ-FLA-NP had a 100% survival rate with significant suppression of tumor
growth. Histopathological and immunohistochemical studies also demonstrated that
CS-TMZ-FLA-NP had superior anticancer activity compared to the other two
treatments. Our results indicate that CS-TMZ-FLA-NP can effectively facilitate
targeting to human lung cancer cell lines in vitro and to lung tumors in vivo in
a sustained manner and so improve the therapeutic efficacy of TMZ.
PMID- 29340057
TI - Aberrant expression of STYK1 and E-cadherin confer a poor prognosis for
pancreatic cancer patients.
AB - Previous studies showed that aberrant Serine/threonine/tyrosine kinase 1 (STYK1,
also known as NOK) or/and E-cadherin were involved in the progression of some
types of human cancers. However, whether they contributed to the development of
pancreatic cancer was unknown. Here, we investigated the prognostic significance
of aberrant STYK1 and E-cadherin in pancreatic cancer. Our results showed that
STYK1 expression increased while E-cadherin decreased in pancreatic cancer
tissues compared with normal pancreas tissues. STYK1 level was positively
correlated with lymph node metastasis and clinical stage in pancreatic cancer
patients. E-cadherin expression was inversely correlated with STYK1 expression in
pancreatic cancer tissue samples. Patients with high STYK1 and low E-cadherin
expression had the worst prognosis. In addition, STYK1 knockdown in pancreatic
cancer cell lines inhibited cell proliferation, enhanced cell apoptosis, induced
cell cycle arrest, and prohibited cell migration, while STYK1 over-expression
showed the opposite effects. Silencing STYK1 also increased E-cadherin expression
and inhibited epithelial-to-mesenchymal transition (EMT) and p-p38 expression in
vitro. Over-expression had showed the opposite trends, and treatment with p38
inhibitor, SB203580, could reverse the trends. Thus, STYK1 repressed E-cadherin
expression and promoted EMT, mediated by p38 MAPK signaling pathway, which was
the possible mechanism for STYK1-mediated pancreatic cancer cell proliferation
and migration. In summary, our results showed that STYK1 might be a prognostic
marker for pancreatic cancer patients and might be a novel strategy for the
treatment of pancreatic cancer.
PMID- 29340058
TI - A multicenter prospective phase II study of first-line modified FOLFIRINOX for
unresectable advanced pancreatic cancer.
AB - Background: FOLFIRINOX (FX) has been reported as an effective treatment for
unresectable advanced pancreatic cancer. However, FX is associated with a high
incidence of adverse events (AEs). A previous phase II study in Japan showed high
incidences of hematological AEs, including febrile neutropenia (22.2%). A
modified FX regimen (mFX) may decrease the rates of AEs and be more effective
than FX by improving the treatment compliance. Aims: To assess the safety and
efficacy of first-line mFX for unresectable advanced pancreatic cancer. Patients
and methods: This was as a multicenter prospective phase II study in chemotherapy
naive Japanese patients with pathologically confirmed unresectable advanced
pancreatic adenocarcinoma or adenosquamous carcinoma. Treatment with mFX (85
mg/m2 oxaliplatin, 150 mg/m2 irinotecan, and 200 mg/m2 l-leucovorin, followed by
46-h continuous infusion of 2400 mg/m2 5-fluorouracil) was administered every 2
weeks. The primary endpoint was the response rate. The secondary endpoints were
overall survival, progression-free survival, and safety. Results: Thirty-one
patients (18 men; median age, 64 years) were enrolled. A median of 13 treatment
cycles were administered during a median follow-up period of 14.2 months. The
response rate, median overall survival, and median progression-free survival were
38.7%, 14.9 months, and 7.0 months, respectively. Grade 3 or 4 AEs included
neutropenia (83.9%), febrile neutropenia (16.1%), peripheral sensory neuropathy
(9.7%), thrombocytopenia (6.5%), diarrhea (6.5%), anorexia (6.5%), and vomiting
(3.2%). Conclusion: Compared to FX, mFX may result in fewer Grade 3 or 4 non
hematological AEs, with a comparable response rate. However, further efforts
might be required to reduce hematological AEs.
PMID- 29340059
TI - MicroRNA-95 promotes myogenic differentiation by down-regulation of aminoacyl
tRNA synthase complex-interacting multifunctional protein 2.
AB - MicroRNA-95 (miR-95) is well known for its ability to promote the proliferation
of a variety of cancer cells, but its function in skeletal muscle development has
not been reported so far. Our laboratory has recently generated genetically
engineered Meishan pigs containing a loss-of-function myostatin (MSTN) mutant
(MSTN-/-). These MSTN-/- pigs grow and develop normally but show clear double
muscle phenotype as observed in Belgian cattle. We observed that the expression
of miR-95 was up-regulated in the longissimus dorsi from MSTN-/- Meishan pigs at
day 65 during embryo development. In this study, we investigated the role of miR
95 in the myogenic differentiation using a murine myoblast cell line C2C12. Our
results revealed that miR-95 may play a very important role in regulating the
expression of myogenic differentiation marker genes myosin heavy chain (MHC) and
myogenin. By use of bioinformatical analysis and luciferase reporter gene assay,
aminoacyl-tRNA synthase complex-interacting multifunctional protein 2 (AIMP2)
gene was identified as a miR-95 target gene involved in myogenic differentiation.
Our results indicated that higher miR-95 expression level leads to lower level of
AIMP2 protein expression. When the endogenous expression of AIMP2 is inhibited by
siRNA, the expression levels of myogenic differentiation marker genes MHC and
myogenin increased, implying that AIMP2 negatively regulates myogenic
differentiation. Taken together, it is likely that miR-95 promotes myogenic
differentiation in C2C12 myoblasts and may play a positive functional role in
skeletal muscle development by down regulating the expression of AIMP2 at protein
level.
PMID- 29340060
TI - Assessment of antimicrobial and wound healing effects of Brevinin-2Ta against the
bacterium Klebsiella pneumoniae in dermally-wounded rats.
AB - Antimicrobial peptides (AMPs) are regarded as promising alternatives for
antibiotics due to their inherent capacity to prevent microbial drug resistance.
Amphibians are rich source of bioactive molecules, which provide numerous AMPs
with various structures as drug candidates. Here, we isolated and identified a
novel AMP Brevinin-2Ta (B-2Ta) from the skin secretion of the European frog,
Pelophylax kl. esculentus. In vitro studies revealed that it showed broad
antimicrobial activities against S. aureus, E. coli and C. albicans with low
cytotoxicity to erythrocytes. Furthermore, we examined the anti-inflammation
effect in vivo by using Klebsiella pneumoniae-infected Sprague-Dawley (SD) rats.
The wound closure outcomes revealed that B-2Ta effectively restrained the
bacterial infection at a dose of 10 times minimal inhibitory concentration (MIC)
during the 14 days of the wound healing process. Ultra-structure analyses showed
that B-2Ta caused structural damage to the microorganism, and bacterial culture
found that the number of microbes was significantly reduced by the end of
treatment. Immunohistochemistry for the inflammatory marker IL-10 and the
endothelial cell marker CD31 suggested positive effects on inflammatory status
and epithelial migration and angiogenesis following treatment of the infected
granulation tissues with B-2Ta. These results exhibited the continuous phase of
inflammation reduction and wound healing acceleration in the B-2Ta-modulated re
epithelialisation of K. pneumoniae infected rats. Taken together, these data
demonstrated that B-2Ta has great potential to be developed as antibacterial
agents in clinic.
PMID- 29340062
TI - Correlation of psychooncological distress- screening and quality of life
assessment in neurosurgical patients.
AB - Background: Cerebral tumors are associated with high rates of anxiety, depression
and reduced health related quality of life. But still psychooncological screening
instruments are not implemented in the daily routine of neurosurgical
departments. In contrast the EORTC QLQ-C30/ EORTC QLQ- BN20 questionnaire is
often used to evaluate quality of life in the framework of clinical studies. We
were therefore interested, if conspicuous distress screening results are also
reflected by HRQOL assessment. Patients and Methods: Patients who were electively
admitted for surgery of intracranial lesions were screened for their
psychooncological distress using two self-assessment instruments (Hospital
Anxiety and Depression Scale (HADS) and Distress Thermometer (DT)) and one
external assessment questionnaire (Psychooncological base documentation (PO
Bado). Results were correlated with three subscales of the EORTC-QLQ-C30 and
EORTC-QLQ-BN20 questionnaire. Results: From October 2013 to March 2015, 594
patients were admitted for elective cranial neurosurgical procedure. 489
neurosurgical patients were screened for increased distress. Data from 450
patients could be correlated with the EORTC-QLQ-C30 and EORTC-QLQ-BN20. In 265
patients screening revealed increased distress. A concurrent reduced global
health /higher rates of future uncertainty and conspicuous distress screening
results are found in 173 patients (69.5%) compared to 30.5% of patients (n= 76)
with unremarkable screening. Increased distress screening was highly significant
with increased level of future uncertainty as well as decreased level of quality
of life and global health (p<0.0001). Conclusion: Psychooncological distress is
accompanied by reduced quality of life, global heath and increased future
uncertainty. Therefore HQOL assessment can be helpful identifying patients with
increased distress.
PMID- 29340061
TI - Analysis of the mutational landscape of classic Hodgkin lymphoma identifies
disease heterogeneity and potential therapeutic targets.
AB - Defining the mutational landscape of classic Hodgkin lymphoma is still a major
research goal. New targeted next-generation sequencing (NGS) techniques may
identify pathogenic mechanisms and new therapeutic opportunities related to this
disease. We describe the mutational profile of a series of 57 cHL cases, enriched
in Hodgkin and Reed-Sternberg (HRS) cells. Overall, the results confirm the
presence of strong genomic heterogeneity. However, several variants were
consistently detected in genes related to relevant signaling pathways, such as GM
CSF/IL-3, CBP/EP300, JAK/STAT, NF-kappaB, and numerous variants of genes
affecting the B-cell receptor (BCR) pathway, such as BTK, CARD11, BCL10, among
others. This unexpectedly high prevalence of mutations affecting the BCR pathway
suggests some requirement for active BCR signaling for cHL cell viability.
Additionally, incubation of a panel of cHL cellular models with selective BTK
inhibitors in vitro constrains cell proliferation and causes cell death. Our
results indicate new pathogenic mechanisms and therapeutic opportunities in this
disease.
PMID- 29340064
TI - Antitumor activity of resveratrol against human osteosarcoma cells: a key role of
Cx43 and Wnt/beta-catenin signaling pathway.
AB - Osteosarcoma is a high-grade bone sarcoma with strong invasive ability. However,
treatment with traditional chemotherapeutic drugs is limited by low tolerability
and side effects. Resveratrol has been reported previously to have selective
antitumor effect on various tumor cells while little is known about its effects
and underlying mechanism in osteosarcoma biology. In this study, we found that
resveratrol inhibits proliferation and glycolysis, induces apoptosis and reduces
the invasiveness of U2-OS cells in vitro. After treatment with resveratrol, the
expression of related Wnt/beta-catenin signaling pathway target genes, such as
beta-catenin, c-myc, cyclin D1, MMP-2 and MMP-9, was downregulated and an
increased E-cadherin level was observed as well. Additionally, the dual
luciferase assay results also indicated that resveratrol suppressed the activity
of Wnt/beta-catenin signaling pathway. Interestingly, we noticed that the
expression of connexin 43 (Cx43) increased with the prolongation of resveratrol
treatment time. To further investigate the relationship between Cx43 and the
Wnt/beta-catenin signaling pathway in osteosarcoma, we used lentiviral-mediated
shRNA to knockdown the expression of Cx43. Knockdown of Cx43 activated the
Wnt/beta-catenin signaling pathway, promoted proliferation and invasion, and
inhibited apoptosis of U2-OS cells. Taken together, our results demonstrate that
the antitumor activity of resveratrol against U2-OS cells in vitro occurs through
up-regulating Cx43 and E-cadherin, and suppressing the Wnt/beta-catenin signaling
pathway. Moreover, Cx43 expression is negatively related to the activity of the
Wnt/beta-catenin pathway in U2-OS cells.
PMID- 29340063
TI - A molecular signature of dormancy in CD34+CD38- acute myeloid leukaemia cells.
AB - Dormant leukaemia initiating cells in the bone marrow niche are a crucial
therapeutic target for total eradication of acute myeloid leukaemia. To study
this cellular subset we created and validated an in vitro model employing the
cell line TF-1a, treated with Transforming Growth Factor beta1 (TGFbeta1) and a
mammalian target of rapamycin inhibitor. The treated cells showed decreases in
total RNA, Ki-67 and CD71, increased aldehyde dehydrogenase activity, forkhead
box 03A (FOX03A) nuclear translocation and growth inhibition, with no evidence of
apoptosis or differentiation. Using human genome gene expression profiling we
identified a signature enriched for genes involved in adhesion,
stemness/inhibition of differentiation and tumour suppression as well as
canonical cell cycle regulation. The most upregulated gene was the osteopontin
coding gene SPP1. Dormant cells also demonstrated significantly upregulated beta
3 integrin (ITGB3) and CD44, as well as increased adhesion to their ligands
vitronectin and hyaluronic acid as well as to bone marrow stromal cells.
Immunocytochemistry of bone marrow biopsies of AML patients confirmed the
positive expression of osteopontin in blasts near the para-trabecular bone
marrow, whereas osteopontin was rarely detected in mononuclear cell isolates.
Unsupervised hierarchical clustering of the dormancy gene signature in primary
acute myeloid leukaemia samples from the Cancer Genome Atlas identified a cluster
enriched for dormancy genes associated with poor overall survival.
PMID- 29340065
TI - Integrating gene and lncRNA expression to infer subpathway activity for tumor
analyses.
AB - LncRNAs acting as miRNA sponges to indirectly regulate mRNAs is a novel layer of
gene regulation, therefore, it is necessary to integrate lncRNA and gene levels
for interpreting tumor biological mechanism. In this study, we developed a lncRNA
gene integrated strategy to infer functional activities for tumor analyses at the
subpathway level. In this strategy, we reconstructed subpathway graphs by
embedding lncRNA components and considered the expression levels of both genes
and lncRNAs to infer subpathway activities for each tumor sample. And the
activities were applied to three aspects of tumor analyses; First, the subpathway
activities across tumor samples of five tumor types were analyzed, and it was
observed that the samples with consistent subpathway activities were derived from
the same or similar tumor types. Also, the subpathway activities could stratify
samples into several subtypes which has different clinical characterization, e.g.
survival status. Second, the subpathway activities between tumor and normal
samples were analyzed, and the comparative results showed that subpathway
activities displayed more specificities than entire pathway activities. Finally,
based on the subpathway activities, we identified prognostic subpathways for lung
cancer. Our subpathway-based signatures shared significant overlap with
enrichment analysis results and displayed predictive power in the independent
testing sets. In conclusion, our integrated strategy provided a framework to
infer subpathway activities for tumor analyses and identify subpathway signatures
for clinical use.
PMID- 29340066
TI - Clinicopathological and prognostic significance of SDC1 overexpression in breast
cancer.
AB - Background: Breast cancer is the leading cause of cancer death among global
women, and its early diagnosis and treatment are very urgent. Syndecan-1 (SDC1)
is a heparin sulfate proteoglycan, which has been linked with the prognosis and
treatment response in a various tumor type. To investigate whether SDC1 can serve
as a prognostic indictor in breast cancer, bioinformatic analyses were performed
in the present study. Methods: SDC1 expression was assessed using Oncomine
analysis. Kaplan-Meier Plotter and bc-GenExMiner were performed to identify the
prognostic roles of SDC1 in breast cancer. COSMIC analysis and cBioPortal
database were performed to analysis the mutations of SDC1. The heat map and
methylation status of SDC1 were identified by performing the UCSC. Results: We
found that SDC1 was more frequently overexpressed in breast cancer than their
normal tissues and its expression might be negatively related with some CpG
sites. Meanwhile, pooled data suggested that SDC1 mRNA expression is associated
worse prognosis of breast cancer. Following data mining in multiple big databases
confirmed a positive correlation between SDC1 mRNA expression and PLAU mRNA
expression in breast cancer tissues. In addition, high SDC1 expression is
associated with increased risked of age, nodal, HER2 and higher SBR grade status.
Conclusion: Our findings suggest that overexpressed SDC1 was identified in breast
cancer than in matched normal tissues and is associated with methylation status
of SDC1 promoter. Additionally, SDC1 is positively associated with PLAU and might
act as a potential prognostic indicator for breast cancer.
PMID- 29340067
TI - The effects of tumor necrosis factor-alpha (TNF-alpha) rs1800629 and rs361525
polymorphisms on sepsis risk.
AB - This meta-analysis of 23 eligible articles comprehensively and quantitatively
evaluated the effects of tumor necrosis factor-alpha (TNF-alpha) rs1800629 and
rs361525 polymorphisms on sepsis risk. We found that TNF-alpha rs1800629 was
associated with increased sepsis risk in the overall population in four genetic
models, including A vs. G (P<0.001, odds ratio (OR)=1.32), GA vs. GG (P<0.001,
OR=1.46), GA+AA vs. GG (P<0.001, OR=1.46), and carrier A vs. carrier G (P<0.001,
OR=1.32). Subgroup analyses showed a similar result for Asian patients (all
P<0.05, OR>1). TNF-alpha rs361525 was also associated with increased sepsis risk
in Asian patients in the four genetic models (all P<0.05, OR>1). Begg's and
Egger's tests excluded large publication bias, and sensitivity analysis indicated
stable results. Our results suggest that the G/A genotype of TNF-alpha rs1800629
and rs361525 increases sepsis risk in an Asian population.
PMID- 29340068
TI - Chaperonin containing TCP-1 subunit 3 is critical for gastric cancer growth.
AB - Background: Members of eukaryotic chaperonin family are essential for cell
survival. Dysregulation of Chaperonin containing TCP-1 subunit 3 (CCT3) has been
implicated in the development of several types of cancers. However, the role of
CCT3 in the development of gastric cancer has yet to be determined. Methods: The
expression patterns of CCT3 in the surgical specimens from 26 gastric cancer
patients were evaluated using immunohistochemistry methods. To study the possible
roles of CCT3 in the growth and survival of gastric cancer cells, RNA
interference was used to knockdown CCT3 expression in gastric cancer cell lines
BGC-823 and MGC-803. The effects of CCT3 knockdown on cancer cell proliferation,
apoptosis and in vivo growth were examined. Finally, gene expression changes
related to CCT3 knockdown were studied using gene array analysis and western
blotting. Results: Higher level of CCT3 expression was detected in the gastric
cancer tissue compared to adjacent non-cancerous epithelium. Knockdown of CCT3
inhibited proliferation and colony formation while promoted apoptosis of gastric
cancer cells in vitro. Gastric cancer cells exhibited lower growth potential in
nude mice when CCT3 expression was suppressed. Gene expression analysis showed
that CCT3 knockdown was associated with down-regulation of mitogen-activated
protein kinase kinase kinase 7, cell division cycle 42, cyclin D3 and up
regulation of cyclin-dependent kinase 2 and 6. Conclusion: Our results suggested
that CCT3 played a critical role in gastric cancer growth and survival. Further
studies on the mechanisms of CCT3 function is mandated to develop novel cancer
treatment targeting CCT3.
PMID- 29340069
TI - Methylenetetrahydrofolate reductase tagging polymorphisms are associated with
risk of esophagogastric junction adenocarcinoma: a case-control study involving
2,740 Chinese Han subjects.
AB - In this study, we aimed to determine the potential association of MTHFR tagging
single nucleotide polymorphisms (SNPs) with risk of developing esophagogastric
junction adenocarcinoma (EGJA). MTHFR rs1801133 G>A, rs3753584 T>C, rs4845882
G>A, rs4846048 A>G and rs9651118 T>C polymorphisms were genotyped in 1,677
healthy individuals and 1,063 patients with EGJA. We found that MTHFR rs1801133
G>A polymorphism was significantly associated with the risk of developing EGJA
(AA vs. GG: adjusted P = 0.001; GA/AA vs. GG: adjusted P = 0.007 and AA vs.
GA/GG: adjusted P = 0.001). However, for MTHFR rs4845882 G>A polymorphism, the
decreased risk of EGJA was found in two genetic models (AA vs. GG: adjusted P =
0.002 and AA vs. GA/GG: adjusted P = 0.005). In addition, for MTHFR rs3753584 T>C
and rs9651118 T>C polymorphisms, a tendency to decreased risk of EGJA was noted.
In a subgroup analysis, a significantly decreased risk of EGJA in <64 years
subgroup was identified. We found that MTHFR
Grs1801133Trs3753584Grs4845882Ars4846048Crs9651118,
Grs1801133Crs3753584Ars4845882Ars4846048Trs9651118 and
Grs1801133Trs3753584Ars4845882Grs4846048Trs9651118 haplotypes significantly
decreased the risk of EGJA (P = 0.002, P < 0.001 and P = 0.038, respectively). In
conclusion, our study demonstrates that MTHFR rs1801133 G>A may be associated
with the increased risk of EGJA. Meanwhile, MTHFR rs3753584 T>C, rs4845882 G>A
and rs9651118 T>C polymorphisms and haplotypes may decrease the risk of EGJA in
Eastern Chinese Han population. Further studies with large sample size and
detailed gene-environmental data are needed to validate our conclusion.
PMID- 29340070
TI - A novel orally available Syk/Src/Jak2 inhibitor, SKLB-850, showed potent anti
tumor activities in B cell lymphoma (BCL) models.
AB - B cell lymphoma (BCL) is the most frequently diagnosed type of non-Hodgkin
lymphoma (NHL), and accounts for about 4% of all cancers in the USA. Kinases
spleen tyrosine kinase (Syk), Src, and Janus kinase 2 (JAK2) have been thought as
potential targets for the treatment of BCL. We have recently developed a
multikinase inhibitor, SKLB-850, which potently inhibits Syk, Src, and JAK2. The
aim of this study is to investigate the anti-BCL activities and mechanisms of
action of SKLB-850 both in vitro and in vivo. Our results showed that SKLB-850
significantly inhibited BCL cell proliferation, and induced apoptosis of BCL
cells. It could considerably decrease the secretion of chemokines CCL3, CCL4, and
CXCL12. Oral administration of SKLB-850 considerably suppressed the tumor growth
in BCL xenograft models (Ramos and HBL-1) in a dose-dependent manner.
Immunohistochemistry of tumor tissues showed that SKLB-850 efficiently inhibited
the activation of Syk/ERK, Src/FAK and JAK2/Stat3 pathways. Collectively, SKLB
850 could be a promising agent for the treatment of BCL, hence deserving further
study.
PMID- 29340071
TI - Hypoxia-inducible factor-1alpha regulates microglial functions affecting neuronal
survival in the acute phase of ischemic stroke in mice.
AB - Cells universally adapt to ischemic conditions by turning on a transcription
factor hypoxia-inducible factor (HIF), in which its role is known to differ
widely across many different types of cells. Given that microglia have been
reported as an essential mediator of neuroinflammation in many brain diseases, we
examined the role of HIF in microglia in the progression of an acute phase of
ischemic stroke by challenging our novel strains of myeloid-specific Hif-1alpha
or Hif-2alpha knockout (KO) mice created by Cre-loxP system via middle cerebral
artery occlusion (MCAO). We observed that Hif-1alpha but not Hif-2alpha KO mice
exhibited an improved recovery compared to wild-type (WT) mice determined by
behavioral tests. Immunostaining analyses revealed that there were increased
numbers of both mature and immature neurons while microglia and apoptotic cells
were significantly decreased in the dentate gyrus of Hif-1alpha KO mice following
MCAO. By isolating microglia with fluorescence-activated cell sorter, we found
that HIF-1alpha-deficient microglia were impaired in phagocytosis, reactive
oxygen species (ROS) production, and tumor necrosis factor-alpha (TNF-alpha)
secretion. We further observed a significant decrease in the expression of Cd36
and milk fat globule-epidermal growth factor 8 (Mfg-e8) genes, both of which
contain hypoxia-responsive element (HRE). Knocking down either of these genes in
BV2 microglial cells was sufficient to abrogate HIF-mediated increase in
phagocytosis, production of intracellular ROS, or TNF-alpha secretion. Our
results therefore suggest that HIF-1alpha in microglia is a novel therapeutic
target to protect neuronal survival following an acute phase of ischemic stroke.
PMID- 29340072
TI - Hyperbaric oxygen protects against myocardial reperfusion injury via the
inhibition of inflammation and the modulation of autophagy.
AB - Our previous study demonstrated that hyperbaric oxygen (HBO) preconditioning
protected against myocardial ischemia reperfusion injury (MIRI) and improved
myocardial infarction. However, HBO's effect on MIRI-induced inflammation and
autophagy remains unclear. In this study, we investigate the potential impact and
underlying mechanism of HBO preconditioning on an MIRI-induced inflammatory
response and autophagy using a ligation of the left anterior descending (LAD)
coronary artery rat model. Our results showed that HBO restored myocardial enzyme
levels and decreased the apoptosis of cardiomyocytes, which were induced by MIRI.
Moreover, HBO significantly suppressed MIRI-induced inflammatory cytokines. This
effect was associated with the inhibition of the TLR4-nuclear factor kappa-B (NF
kappaB) pathway. Interestingly, lower expression levels of microtubule-associated
protein 1 light chain 3B (LC3B) and Beclin-1 were observed in the HBO-treatment
group. Furthermore, we observed that HBO reduced excessive autophagy by
activating the mammalian target of the rapamycin (mTOR) pathway, as evidenced by
higher expression levels of threonine protein kinase (Akt) and phosphorylated
mTOR. In conclusion, HBO protected cardiomocytes during MIRI by attenuating
inflammation and autophagy. Our results provide a new mechanistic insight into
the cardioprotective role of HBO against MIRI.
PMID- 29340073
TI - YM155 exerts potent cytotoxic activity against quiescent (G0/G1) multiple myeloma
and bortezomib resistant cells via inhibition of survivin and Mcl-1.
AB - YM155, a novel small molecule inhibitor of survivin, shows broad anticancer
activity. Here, we have focused on the cytotoxic activity of YM155 against
multiple myeloma (MM) including cytokinetically quiescent (G0/G1) cells and
bortezomib resistant cells. YM155 strongly inhibited the growth of MM cell lines
with the IC50 value of below 10 nM. YM155 also showed potent anti-myeloma
activity in mouse xenograft model. YM155 suppressed the expression of survivin
and rapidly directed Mcl-1 protein for proteasome degradation. YM155 abrogated
the interleukin-6-induced STAT3 phosphorylation, subsequently blocked Mcl-1
expression and induced apoptosis in MM cells. Triple-color flow cytometric
analysis revealed that YM155 potently induced cell death of MM cells in G0 phase.
Quiescent primary MM cells were also sensitive to YM155. We established
bortezomib-resistant MM cell line, U266/BTZR1, which possess a point mutation
G322A. YM155 exhibited similar cytotoxic potency against U266/BTZR1 compared with
parental cells. Interestingly, survivin expression was markedly elevated in
U266/BTZR1 cells. Treatment with YM155 significantly down-regulated this
increased survivin and Mcl-1 expression in U266/BTZR1 cells. In conclusion, our
data indicate that YM155 exhibits potent cytotoxicity against quiescent (G0/G1)
MM cells and bortezomib-resistant cells. These unique features of YM155 may be
beneficial for the development of new therapeutic strategies to eliminate
quiescent MM cells and overcome bortezomib resistance.
PMID- 29340074
TI - Identification of novel diagnostic biomarkers for thyroid carcinoma.
AB - Thyroid carcinoma (THCA) is the most universal endocrine malignancy worldwide.
Unfortunately, a limited number of large-scale analyses have been performed to
identify biomarkers for THCA. Here, we conducted a meta-analysis using 505 THCA
patients and 59 normal controls from The Cancer Genome Atlas. After identifying
differentially expressed long non-coding RNA (lncRNA) and protein coding genes
(PCG), we found vast difference in various lncRNA-PCG co-expressed pairs in THCA.
A dysregulation network with scale-free topology was constructed. Four molecules
(LA16c-380H5.2, RP11-203J24.8, MLF1 and SDC4) could potentially serve as
diagnostic biomarkers of THCA with high sensitivity and specificity. We further
represent a diagnostic panel with expression cutoff values. Our results
demonstrate the potential application of those four molecules as novel
independent biomarkers for THCA diagnosis.
PMID- 29340075
TI - Extracting microtentacle dynamics of tumor cells in a non-adherent environment.
AB - During metastasis, tumor cells dynamically change their cytoskeleton to traverse
through a variety of non-adherent microenvironments, including the vasculature or
lymphatics. Due to the challenges of imaging drift in non-adhered tumor cells,
the dynamic cytoskeletal phenotypes are poorly understood. We present a new
approach to analyze the dynamic cytoskeletal phenotypes of non-adhered cells that
support microtentacles (McTNs), which are cell surface projections implicated in
metastatic reattachment. Combining a recently-developed cell tethering method
with a novel image analysis framework allowed McTN attribute extraction. Full
cell outlines, number of McTNs, and distance of McTN tips from the cell body
boundary were calculated by integrating a rotating anisotropic filtering method
for identifying thin features with retinal segmentation and active contour
algorithms. Tethered cells behave like free-floating cells; however tethering
reduces cell drift and improves the accuracy of McTN measurements. Tethering
cells does not significantly alter McTN number, but rather allows better
visualization of existing McTNs. In drug treatment experiments, stabilizing
tubulin with paclitaxel significantly increases McTN length, while destabilizing
tubulin with colchicine significantly decreases McTN length. Finally, we quantify
McTN dynamics by computing the time delay autocorrelations of 2 composite
phenotype metrics (cumulative McTN tip distance, cell perimeter:cell body ratio).
Our automated analysis demonstrates that treatment with paclitaxel increases
total McTN amount and colchicine reduces total McTN amount, while paclitaxel also
reduces McTN dynamics. This analysis method enables rapid quantitative
measurement of tumor cell drug responses within non-adherent microenvironments,
using the small numbers of tumor cells that would be available from patient
samples.
PMID- 29340076
TI - Mitochondrial ROS activates ERK/autophagy pathway as a protected mechanism
against deoxypodophyllotoxin-induced apoptosis.
AB - Deoxypodophyllotoxin (DPT) is a naturally occurring flavolignan isolated from
Anthriscus sylvestris. Recently, it has been reported that DPT inhibits tubulin
polymerization and induces G2/M cell cycle arrest followed by apoptosis through
multiple cellular processes. Despite these findings, details regarding the
cellular and molecular mechanisms underlying the DPT-mediated cell death have
been poorly understood. To define a mechanism of DPT-mediated cell death
response, we examined whether DPT activates signaling pathways for autophagy and
apoptosis. We demonstrated that DPT inhibited cell viability and induced
apoptosis in prostate cancer cell lines, as evidenced by a mitochondrial membrane
potential and expression of apoptosis-related proteins. Reactive oxygen species
(ROS), primarily generated from the mitochondria, play an important role in
various cellular responses, such as apoptosis and autophagy. DPT significantly
triggered mitochondrial ROS, which were detected by MitoSOX, a selective
fluorescent dye of mitochondria-derived ROS. Furthermore, DPT induced autophagy
through an up-regulation of autophagic biomarkers, including a conversion of
microtubule-associated protein 1 light chain 3 - I (LC3-I) into LC3-II and a
formation of acidic vesicular organelles. Moreover, mitochondrial ROS promoted
AKT-independent autophagy and ERK signaling. The inhibition of autophagy with 3
methyladenine or LC3 knockdown enhanced DPT-induced apoptosis, suggesting that an
autophagy plays a protective role in cell survival against apoptotic prostate
cancer cells. Additionally, the results from an in vivo xenograft model confirmed
that DPT inhibited tumor growth by regulating the apoptosis- and autophagy
related proteins.
PMID- 29340077
TI - LRP6 targeting suppresses gastric tumorigenesis via P14ARF-Mdm2-P53-dependent
cellular senescence.
AB - NLRP6, a member of the Nod-like receptor family, protects against chemically
induced intestinal injury and colitis-associated colon cancer. However, the
cellular mechanisms involved in this NLRP6-mediated protection remain unclear.
Here, we show that NLRP6 was down-regulated in approximately 75% of primary
gastric cancer cases and exhibited significant associations with advanced
clinical-stage lymph node metastasis and poor overall survival. Functional
studies established that ectopic overexpression or down-regulation of NLRP6
inhibited cancer cell proliferation by inducing cell cycle arrest at the G1 phase
via P21 and Cyclin D1 both in vitro and in vivo. Activation of the P14ARF-P53
pathway played a crucial role in the observed cellular senescence. We further
demonstrated that ectopic overexpression of NLRP6 combined with inactivation of
NF-kappaB(p65) and Mdm2 activates P14ARF-P53 to promote the senescence of gastric
cancer cells. These findings indicate that NLRP6 functions as a negative
regulator of gastric cancer and offer a potential new option for preventing
gastric cancer.
PMID- 29340078
TI - Differential gene expression profiles between two subtypes of ischemic stroke
with blood stasis syndromes.
AB - Ischemic stroke is a cerebrovascular thrombotic disease with high morbidity and
mortality. Qi deficiency blood stasis (QDBS) and Yin deficiency blood stasis
(YDBS) are the two major subtypes of ischemic stroke according to the theories of
traditional Chinese medicine. This study was conducted to distinguish these two
syndromes at transcriptomics level and explore the underlying mechanisms. Male
rats were randomly divided into three groups: sham group, QDBS/MCAO group and
YDBS/MCAO group. Morphological changes were assessed after 24 h of reperfusion.
Microarray analysis with circulating mRNA was then performed to identify
differential gene expression profile, gene ontology and pathway enrichment
analyses were carried out to predict the gene function, gene co-expression and
pathway networks were constructed to identify the hub biomarkers, which were
further validated by western blotting and Tunel staining analysis. Three subsets
of dysregulated genes were acquired, including 445 QDBS-specific genes, 490 YDBS
specific genes and 1676 blood stasis common genes. Our work reveals for the first
time that T cell receptor, MAPK and apoptosis pathway were identified as the hub
pathways based on the pathway networks, while Nfkappab1, Egfr and Casp3 were
recognized as the hub genes by co-expression networks. This research helps
contribute to a clearer understanding of the pathological characteristics of
ischemic stroke with QDBS and YDBS syndrome, the proposed biomarkers might
provide insight into the accurate diagnose and proper treatment for ischemic
stroke with blood stasis syndrome.
PMID- 29340079
TI - High expression of angiogenic factor AGGF1 is an independent prognostic factor
for hepatocellular carcinoma.
AB - Background: Angiogenesis plays a critical role in tumor growth and metastasis.
Angiogenic factor with G patch and FHA domains 1 (AGGF1) has been recently
identified as a novel initiator of angiogenesis. However, the function and the
prognostic values of AGGF1 in hepatocellular carcinoma remain poorly understood.
Our aim is to provide more information to assist design the angiogenesis therapy
that targets AGGF1 in HCC. Results: AGGF1-positive frequency in HCC tissues was
significantly higher than in peritumor tissues. The high expression of AGGF1
expression in HCC tissue was well associated with the increased expression of
VEGF and the high microvessel density (MVD). AGGF1 expression predicts a poor
prognosis and AGGF1 was an independent prognostic factor for DFS. Methods: The
expression levels of AGGF1, vascular endothelial growth factor (VEGF) and
microvessel density (MVD) were identified by immunohistochemistry in 79 HCC tumor
tissues and 24 corresponding peritumor tissues. The expression level of AGGF1 and
MVD were quantified by counting the positively stained endothelial cells in the
HCC and the peritumor tissue on the immunohistochemically stained tissue slides.
The prognostic value of AGGF1 was evaluated by survival analysis. Conclusions:
Our study shows that AGGF1 is identified as the independent prognostic factor for
the disease-free survival (DFS) of patients after the surgical resection.
contribute to tumor angiogenesis in HCC, which indicates that AGGF1 may be a new
potential therapeutic target for anti-angiogenesis treatment for patients with
HCC.
PMID- 29340080
TI - Inhibition of tumor necrosis factor signaling attenuates renal immune cell
infiltration in experimental membranous nephropathy.
AB - Idiopathic membranous nephropathy (MN) is an autoimmune-mediated
glomerulonephritis and the most common cause of idiopathic nephrotic syndrome in
adult humans. A tumor necrosis factor alpha (TNF-alpha)-mediated inflammatory
response via TNF receptor 1 (TNFR1) and TNFR2 has been proposed as a pathogenic
factor. In this study, we assessed the therapeutic response to blocking TNF
signaling in experimental MN. Murine MN was induced experimentally by cationic
bovine serum albumin (cBSA); phosphate-buffered saline was used in control mice.
In MN mice, TNF was inhibited by etanercept blocking of TNFR1/TNFR2 or the
preligand assembly domain fusion protein (PLAD.Fc), a small fusion protein that
can preferentially block TNFR1 signaling. Disease severity and possible
mechanisms were assessed by analyzing the metabolic and histopathology profiles,
lymphocyte subsets, immunoglobulin production, oxidative stress, and apoptosis.
cBSA-induced MN mice exhibited typical nephrotic syndrome and renal
histopathology. MN mice given etanercept or PLAD.Fc did not exhibit significant
reduction of proteinuria, amelioration of glomerular lesions, or attenuation of
immune complex deposition. Immune cell subsets, serum immunoglobulin levels,
production of reactive oxygen species, and cell apoptosis in the kidney were not
altered by TNF inhibition. By contrast, MN mice receiving etanercept or PLAD.Fc
exhibited significantly decreased infiltration of immune cells into the kidney.
These results show that the therapeutic effects of blocking TNFR1 and/or TNFR2
signaling in experimental MN are not clinically effective. However, TNF signaling
inhibition significantly attenuated renal immune cell infiltration in
experimental MN.
PMID- 29340081
TI - PCPA protects against monocrotaline-induced pulmonary arterial remodeling in
rats: potential roles of connective tissue growth factor.
AB - The purpose of this study was to investigate the mechanism of monocrotaline (MCT)
induced pulmonary artery hypertension (PAH) and determine whether 4-chloro-DL
phenylalanine (PCPA) could inhibit pulmonary arterial remodeling associated with
connective tissue growth factor (CTGF) expression and downstream signal pathway.
MCT was administered to forty Sprague Dawley rats to establish the PAH model.
PCPA was administered at doses of 50 and 100 mg/kg once daily for 3 weeks via
intraperitoneal injection. On day 22, the pulmonary arterial pressure (PAP),
right ventricle hypertrophy index (RVI) and pulmonary artery morphology were
assessed and the serotonin receptor-1B (SR-1B), CTGF, p-ERK/ERK were measured by
western blot or immunohistochemistry. The concentration of serotonin in plasma
was checked by ELISA. Apoptosis and apoptosis-related indexes were detected by
TUNEL and western blot. In the MCT-induced PAH models, the PAP, RVI, pulmonary
vascular remodeling, SR-1B index, CTGF index, anti-apoptotic factors bcl-xl and
bcl-2, serotonin concentration in plasma were all increased and the pro-apoptotic
factor caspase-3 was reduced. PCPA significantly ameliorated pulmonary arterial
remodeling induced by MCT, and this action was associated with accelerated
apoptosis and down-regulation of CTGF, SR-1B and p-ERK/ERK. The present study
suggests that PCPA protects against the pathogenesis of PAH by suppressing
remodeling and inducing apoptosis, which are likely associated with CTGF and
downstream ERK signaling pathway in rats.
PMID- 29340082
TI - Reciprocal sensitivity of diffuse large B-cell lymphoma cells to Bcl-2 inhibitors
BIRD-2 versus venetoclax.
AB - Bcl-2 is often upregulated in cancers to neutralize the BH3-only protein Bim at
the mitochondria. BH3 mimetics (e.g. ABT-199 (venetoclax)) kill cancer cells by
targeting Bcl-2's hydrophobic cleft and disrupting Bcl-2/Bim complexes. Some
cancers with elevated Bcl-2 display poor responses towards BH3 mimetics,
suggesting an additional function for anti-apoptotic Bcl-2 in these cancers.
Indeed, Bcl-2 via its BH4 domain prevents cytotoxic Ca2+ release from the
endoplasmic reticulum (ER) by directly inhibiting the inositol 1,4,5
trisphosphate receptor (IP3R). The cell-permeable Bcl-2/IP3R disruptor-2 (BIRD-2)
peptide can kill these Bcl-2-dependent cancers by targeting Bcl-2's BH4 domain,
unleashing pro-apoptotic Ca2+-release events. We compared eight "primed to death"
diffuse large B-cell lymphoma cell lines (DLBCL) for their apoptotic sensitivity
towards BIRD-2 and venetoclax. By determining their IC50 using cytometric cell
death analysis, we discovered a reciprocal sensitivity towards venetoclax versus
BIRD-2. Using immunoblotting, we quantified the expression levels of IP3R2 and
Bim in DLBCL cell lysates, revealing that BIRD-2 sensitivity correlated with
IP3R2 levels but not with Bim levels. Moreover, the requirement of intracellular
Ca2+ for BIRD-2- versus venetoclax-induced cell death was different. Indeed,
BAPTA-AM suppressed BIRD-2-induced cell death, but promoted venetoclax-induced
cell death in DLBCL cells. Finally, compared to single-agent treatments,
combining BIRD-2 with venetoclax synergistically enhanced cell-death induction,
correlating with a Ca2+-dependent upregulation of Bim after BIRD-2 treatment. Our
findings suggest that some cancer cells require Bcl-2 proteins at the
mitochondria, preventing Bax activation via its hydrophobic cleft, while others
require Bcl-2 proteins at the ER, preventing cytotoxic Ca2+-signaling events via
its BH4 domain.
PMID- 29340083
TI - Next-generation sequencing-based microRNA profiling of mice testis subjected to
transient heat stress.
AB - This study aimed to investigate the role of microRNA (miRNA) in heat stress
induced spermatogenic impairment. Testes from 15 adult ICR mice subjected to
testicular hyperthermia at 43 degrees C for 30 min and from 15 control mice were
collected and pooled into 3 samples. Isolated RNA from these samples was
subjected to small RNA high-throughput sequencing, and differentially expressed
miRNAs were identified and validated using RT-PCR. The identified miRNAs were
further subjected to Gene Ontology and KEGG analyses, which revealed significant
enrichment for pathways potentially involved in heat stress-induced spermatogenic
impairment. Additionally, a correlation analysis of the relative levels of
validated miRNAs with germ cell apoptosis was performed. Of the 11 miRNAs
identified as differentially expressed, 8 were validated as consistent with
sequencing data. Further analyses suggested that the target genes of those miRNAs
were involved in various pathways (e.g., ribosomal, HIF-1, MAPK) that may be
critical to heat stress-induced testicular damage. Some identified miRNAs,
including miR-449a-3p, miR-92a-1-5p, miR-423-3p, and miR-128-3p, correlated
closely with germ cell apoptosis. The study results reveal a detailed miRNA
profile of heat stress-induced testicular damage and highlight new and
potentially important candidate targets in the process of male infertility.
PMID- 29340084
TI - CRISPR-Cas9 HDR system enhances AQP1 gene expression.
AB - Ionizing radiation (IR) isthe primarytherapeutic tool to treat patients with
cancerous lesions located in the head and neck. In many patients, IR results in
irreversible and severe salivary gland dysfunction or xerostomia. Currently there
are no effective treatment options to reduce the effects of xerostomia. More
recently, salivary gland gene therapy utilizing the water-specific protein
aquaporin 1 (AQP1) has been of great interest to potentially correct salivary
dysfunction. In this study, we used CRISPR-Cas9 gene editing along with the
endogenous promoter of AQP1 within theHEK293 and MDCK cell lines. The successful
integration of the cytomegalovirus (CMV) promoterresultedin a significant
increase of AQP1 gene transcription and translation. Additionalfunctional
experiments involvingthe MDCK cell line confirmedthat over-expressed
AQP1increasedtransmembrane fluid flux indicative of increased intracellular fluid
flux. The off-target effect of designed guided RNA sequence was analyzed and
demonstrateda high specificity for the Cas9 cleavage. Considering the development
of new methods for robust DNA knock-in, our results suggest that endogenous
promoter replacement may be a potential treatment forsalivary gland dysfunction.
PMID- 29340085
TI - 6-(Methylsulfonyl) hexyl isothiocyanate as potential chemopreventive agent:
molecular and cellular profile in leukaemia cell lines.
AB - Numerous laboratory and epidemiological studies show that the risk of developing
several types of cancer can be reduced with the employment of natural substances
that act with multiple mechanisms. In this context, an important role is played
by the isothiocyanates. Recently, 6-(methylsulfonyl)hexyl isothiocyanate (6
MITC), present in the root of Wasabia Japonica, has stimulated the interest of
researchers as a chemopreventive agent. In this particular study we have focused
on evaluating 6-MITC's in vitro cytotoxic, cytostatic and cytodifferentiating
activities, as well as its pro-apoptotic potential. These effects were
investigated by way of flow cytometric analysis of Jurkat and HL-60 cells as well
as of healthy lymphocytes extracted from the blood of AVIS donors, in order to
verify a potential selectivity of action. The results demonstrate that 6-MITC
exerts a stronger cytotoxic effect on tumour cells than on healthy cells. The
apoptosis induction exerted by 6-MITC on transformed cells is triggered by an
extrinsic pathway, as demonstrated by the statistically significant increase in
the percentage of cells with activated caspase-8. It was also observed that 6
MITC is able to limit tumour growth by slowing down and blocking the cell cycle
of Jurkat and HL-60 cells respectively, in a dose- and time-related manner, while
exerting no activity of any kind on the replication of healthy cells. Finally, by
measuring the expression levels of CD-14 and CD-15, 6-MITC showed the ability to
induce cytodifferentiation of HL-60 cells into macrophage and granulocytic
phenotypes.
PMID- 29340086
TI - Up-regulation of lncRNA SNHG1 indicates poor prognosis and promotes cell
proliferation and metastasis of colorectal cancer by activation of the Wnt/beta
catenin signaling pathway.
AB - Recently, the lncRNA small nucleolar RNA host gene (SNHG1) has been exhibited to
be upregulated, which plays a crucial role in the development and prognosis of
several cancers. However, the role of the biology and clinical significance of
SNHG1 in the tumorigenesis of colorectal cancer (CRC) has rarely been reported.
In this work, we firstly found that SNHG1 expression levels were upregulated
aberrantly in colorectal cancer tissues and colorectal cancer cell lines. By
Kaplan-Meier survival analysis, patients with high SNHG1 expression level had
poorer overall survival (OS) and progression-free survival (PFS) than those with
low SNHG1 expression. In multivariate analysis, increased SNHG1 expression was
proved to be an independent unfavorable prognostic indicator for CRC. In vitro
experiments revealed that SNHG1 silencing inhibited the growth and metastasis and
induced apoptosis of CRC cell lines. Finally, we found that SNHG1 may induce the
activation of the WNT/beta-catenin pathway through regulating beta-catenin
expression and transcription factor-4 (TCF-4), cyclin D1 and MMP-9. Altogether,
our findings demonstrated that lncRNA SNHG1, was high expressed in colorectal
cancer tissues and may serve as a tumor oncogene through regulating WNT/beta
catenin signal pathway, which provided a candidate diagnostic biomarker and a
promising therapeutic target for patients with CRC.
PMID- 29340087
TI - Identification of antipsychotic drug fluspirilene as a potential anti-glioma stem
cell drug.
AB - Glioma stem cell (GSC)-targeted therapy is expected to be one of the most
innovative approaches to treat patients with glioblastoma (GBM). A number of the
drugs that restrain the signaling pathway essential for GSC maintenance have been
under clinical trials. Here, we identified fluspirilene, a traditional
antipsychotic drug, as a GSC-targeting agent, selected from thousands of existing
drugs, and investigated its therapeutic effects against GBM with the purpose of
drug repositioning. To develop novel therapeutics targeting GSCs, we initially
screened drug libraries for small-molecule compounds showing a greater efficacy,
compared to that of controls, in inhibiting the proliferation and survival of
different GSC lines using cell proliferation assay. Drugs already reported to
show therapeutic effects against GBM or those under clinical trials were excluded
from subsequent screening. Finally, we found three drugs showing remarkable
antiproliferative effects on GSCs at low concentrations and investigated their
therapeutic effects on GSCs, glioma cell lines, and in a GBM mouse model. Of the
three compounds, fluspirilene demonstrated a significant inhibitory effect on the
proliferation and invasion of glioma cells as well as in the model mice treated
with the drug. These effects were associated with the inactivation of the signal
transducer and activator of transcription 3 (STAT3). Redeveloping of fluspirilene
is a promising approach for the treatment of GBM.
PMID- 29340088
TI - Identification of bladder cancer prognostic biomarkers using an ageing gene
related competitive endogenous RNA network.
AB - Competitive endogenous RNAs (ceRNAs) are a newly proposed RNA interaction
mechanism that has been associated with the initiation and progression of various
cancers. In this study, we constructed an ageing gene related ceRNA network
(AgeingCeNet) in bladder cancer. Network analysis revealed that ageing gene
ceRNAs have a larger degree and closeness centrality than ageing genes
themselves. Notably, the difference of betweenness centrality of ageing genes and
their ceRNAs is not significant, suggesting that the ceRNAs of ageing genes and
ageing genes themselves both play important communication roles in AgeingCeNet.
KEGG pathway enrichment analysis for genes in AgeingCeNet revealed that
AgeingCeNet genes are enriched in cancer pathways and several cancer related
singaling pathways. We also identified 37 core modules from AgeingCeNet using
CFinder software. Next, we identified 2 potential prognostic modules, named
K11M14 and K13M4, whose prognostic ability is better than that of age and gender.
Finally, we identified microRNAs (miRNAs) regulating the two modules, which
include miR-15b-5p, miR-195-5p, miR-30 family members, and several other cancer
related miRNAs. Our study demonstrated that constructing an ageing gene related
ceRNA network is a feasible strategy to explore the mechanism of initiation and
progression of bladder cancer, which might benefit the treatment of this disease.
PMID- 29340089
TI - LncRNA RNCR3 promotes Chop expression by sponging miR-185-5p during MDSC
differentiation.
AB - Myeloid-derived suppressor cells (MDSCs) play a critical role in regulating
immune responses in cancer and other pathological conditions. Mechanism(s)
regulating MDSC differentiation and function is not completely clear, especially
epigenetic regulation. In this study, we found that MDSCs express retinal non
coding RNA3 (RNCR3), and the expression in MDSCs is upregulated by inflammatory
and tumor associated factors. RNCR3 may function as a competing endogenous RNA
(ceRNA) to promote Chop expression by sponging miR-185-5p during MDSC
differentiation. RNCR3 knockdown suppressed differentiation and function of MDSCs
in vitro and in vivo. Quantitative RT-PCR showed that RNCR3 was negatively
regulated by miR-185-5p in MDSCs. MiR-185-5p affected the expansion of MDSCs and
reversed the effect of RNCR3 on MDSC differentiation and function through
directly targeting Chop. Thus, our results suggest a RNCR3/miR-185-5p/Chop
autologously strengthening network to promote MDSC differentiation and
suppressive function in response to extracellular inflammatory and tumor
associated signals.
PMID- 29340090
TI - High glucose enhances the metastatic potential of tongue squamous cell carcinoma
via the PKM2 pathway.
AB - Previous evidence has indicated an increased cancer risk in individuals with
diabetes mellitus (DM). The aim of this study was to investigate the relationship
between DM (high glucose) and tongue squamous cell carcinoma (TSCC) and how high
glucose mediated the metastatic potential of TSCC. The relationship between DM
and TSCC was assessed in a retrospective study. The role and its mechanism of
high glucose on the proliferation, metastatic potential of TSCC were investigated
in vitro and in vivo. The prevalence rate of DM in patients with TSCC was 12.84%,
which was significantly higher than that (9.7%) in the general population in
China. Although no significant difference was observed in the overall survival
(OS) rate, TSCC patients with DM have a 1.38-fold increase in relative risk
affecting 5-year OS compared to patients without DM. High glucose enhanced the
TSCC cell proliferation, migration, invasion and upregulated PKM2 (pyruvate
kinase M2) expression. Whereas, these effect was abolished after knockdown of
PKM2 in TSCC cells. High glucose promoted tumour growth and lung metastasis of
TSCC in a DM animal model. Our results confirm DM as a risk factor for the
development of TSCC. High glucose enhances the metastatic potential of TSCC
through stimulation of the PKM2 pathway.
PMID- 29340091
TI - Fatty acid binding protein 4 enhances prostate cancer progression by upregulating
matrix metalloproteinases and stromal cell cytokine production.
AB - Fatty acid binding protein 4 (FABP4) is an abundant protein in adipocytes, and
its production is influenced by high-fat diet (HFD) or obesity. The prostate
stromal microenvironment induces proinflammatory cytokine production, which is
key for the development and progression of prostate cancer (PCa). Here, we show
that high FABP4 expression and its secretion by PCa cells directly stimulated PCa
cell invasiveness by upregulating matrix metalloproteinases through
phosphatidylinositol 3-kinase and mitogen-activated protein kinase signaling
pathways. In addition, prostate stromal cells augmented PCa cell invasiveness by
secreting interleukin-8 and -6 in response to FABP4. This was abrogated by the
FABP4 specific inhibitor, BMS309403. Furthermore, a mouse xenograft experiment
showed HFD enhanced PCa metastasis and invasiveness by the upregulation of FABP4
and interleukin-8. Clinically, the serum level of FABP4 was significantly
associated with an aggressive type of PCa rather than obesity. Taken together,
FABP4 may enhance PCa progression and invasiveness by upregulating matrix
metalloproteinases and cytokine production in the PCa stromal microenvironment,
especially under HFD or obesity.
PMID- 29340092
TI - First-line dose-dense chemotherapy with docetaxel, cisplatin, folinic acid and 5
fluorouracil (DCF) plus panitumumab in patients with locally advanced or
metastatic cancer of the stomach or gastroesophageal junction: final results and
biomarker analysis from an Italian oncology group for clinical research (GOIRC)
phase II study.
AB - Background: Survival for patients with advanced gastroesophageal cancer (AGC)
using standard treatment regimens is poor. EGFR overexpression is common in AGC
and associated with poor prognosis. We hypothesized that increasing the dose
intensity of chemotherapy and adding panitumumab could improve efficacy. Methods:
HER2 negative, PS 0-1 patients, received up to 4 cycles of panitumumab 6 mg/kg d
1, docetaxel 60 mg/m2 d 1, cisplatin 50 mg/m2 d 1, l-folinic acid 100 mg/m2 d 1
2, followed by 5-FU 400 mg/m2 bolus d 1-2, and then 600 mg/m2 as a 22 h c.i. on d
1-2, q15 d, plus pegfilgrastim 6 mg on d 3. Patients with disease control after 4
cycles received panitumumab until progression. Results: From 05/2010 to 01/2014,
52 patients (75% male; median age 64.5 y; metastatic 90%, locally advanced 10%;
96% adenocarcinoma; 25% GEJ) were recruited. Three CR, 29 PR, 10 SD and 8 PD were
observed, for an ORR by ITT (primary endpoint) of 62% (95% CI, 48%-75%) and a DCR
of 81%. Median TTP was 4.9 months (95% CI, 4.2-7.0) and mOS 10 months (95% CI,
8.2- 13.5). Most frequent G3-4 toxicities: leucopenia (29%), asthenia (27%), skin
rash (25%), neutropenia (19%), anorexia (17%), febrile neutropenia (13%), and
diarrhea (15%). EGFR expression tested both with dd-PCR and FISH was not
associated with any significant clinical benefit from treatment. Conclusions:
Dose-dense DCF plus panitumumab is an active regimen. However, the toxicity
profile of this limits further development. Further research on predictive
biomarkers for treatment efficacy in AGC is required.Clinical trial information:
2009-016962-10.
PMID- 29340093
TI - Leucine mediates autophagosome-lysosome fusion and improves sperm motility by
activating the PI3K/Akt pathway.
AB - Amino acid supplementation is an efficient and effective strategy to increase
sperm quality. In our research, a comparative study was conducted to screen free
amino acids to improve sperm motility, and we found that leucine was the most
efficient one. Leucine treatment increases sperm motility depending on the
activation of PI3K/Akt signaling pathway, while the chemical inhibitor of
PI3K/Akt signal could reduce the amount of pAkt activated by leucine treatment.
Moreover, leucine treatment improved the expression of P62 and LC3-II,
substantially suppressed the autophagy process in zebrafish testis. In vitro
studies showed that leucine could reduce the fusion of autophagosome and lysosome
that was indicated by the co-localization of EGFP-LC3 and lysosome marker. Two
chemical modulators of autophagy, such as LY294002 (the inhibitor of PI3K/Akt
signal) and chloroquine were administered to investigate the process of autophagy
on zebrafish sperm motility. LY294002 inhibited autophagosome formation to
reduced sperm motility, while chloroquine inhibited the fusion of autophagosome
and lysosome to improve sperm motility. Our data suggest that short-term
treatment with leucine could increase zebrafish sperm motility by affecting the
autophagy and inhibiting the fusion of autophagosome and lysosomes, depending on
the activation of PI3K/Akt signaling pathway.
PMID- 29340094
TI - Can urologists introduce the concept of "oligometastasis" for metastatic bladder
cancer after total cystectomy?
AB - We investigated whether the concept of oligometastasis may be introduced to the
clinical management of metastatic bladder cancer patients. Our study population
comprised 128 patients diagnosed with metastatic bladder cancer after total
cystectomy at our 6 institutions between 2004 and 2014. We extracted independent
predictors for identifying a favorable. Occurrence that fulfilled all 4 criteria
which were independently associated with cancer-specific death was defined as
oligometastasis: a solitary metastatic organ; number of metastatic lesions of 3
or less; the largest diameter of metastatic foci of 5cm or less; and no liver
metastasis. We evaluated differences in clinical outcomes between patients with
oligometastasis (oligometastasis group) and those without oligometastasis (non
oligometastasis group). Overall, there were 43 patients in the oligometastasis
group. The 2-year cancer-specific survival rate in the oligometastasis group was
53.3%, which was significantly higher than that in the non-oligometastasis group
(16.1%, p<0.001). A multivariate analysis revealed that non-oligometastasis
(p<0.001), not performing salvage chemotherapy (p<0.001), and not performing
metastatectomy (p=0.028) were independent risk factors for cancer-specific death.
In the subgroup of 83 patients who received salvage chemotherapy, 30 were in the
oligometastasis group. The 2-year cancer-specific survival rate in the
oligometastasis group was 55.0%, which was significantly higher than that in the
non-oligometastasis group (22.0%, p=0.005). Non-oligometastasis (p=0.009) was the
only independent risk factor for cancer-specific death. We presented that
urothelial carcinoma with oligometastasis had a favorable prognosis and responded
to systemic chemotherapy. Oligometastasis may be treated as a separate entity in
the field of metastatic urothelial carcinoma.
PMID- 29340095
TI - Tumoral immune-infiltrate (IF), PD-L1 expression and role of CD8/TIA-1
lymphocytes in localized osteosarcoma patients treated within protocol ISG-OS1.
AB - Background: We hypothesized that immune-infiltrates were associated with superior
survival, and examined a primary osteosarcoma tissue microarrays (TMAs) to test
this hypothesis. Methods: 129 patients (pts) with localized osteosarcoma treated
within protocol ISG-OS1 were included in the study. Clinical characteristics,
expression of CD8, CD3, FOXP3, CD20, CD68/CD163 (tumor associated macrophage,
TAM), Tia-1 (cytotoxic T cell), CD303 (plasmacytoid dendritic cells: pDC),
Arginase-1 (myeloid derived suppressor cells: MDSC), PD-1 on immune-cells (IC),
and PD-L1 on tumoral cells (TC) and IC were analysed and correlated with outcome.
Results: Most of the cases presented tumor infiltrating lymphocytes (TILs) (CD3+
90%; CD8+ 86%). Tia-1 was detected in 73% of the samples. PD-L1 expression was
found in 14% patients in IC and 0% in TC; 22% showed PD-1 expression in IC.With a
median follow-up of 8 years (range 1-13), the 5-year overall survival (5-year OS)
was 74% (95% CI 64-85). Univariate analysis showed better 5-year OS for: a) pts
with a good histologic response to neoadjuvant chemotherapy (p = 0.0001); b) pts
with CD8/Tia1 tumoral infiltrates (p = 0.002); c) pts with normal alkaline
phosphatas (sALP) (p = 0.04). After multivariate analysis, histologic response (p
= 0.007) and CD8/Tia1 infiltration (p = 0.01) were independently correlated with
survival. In the subset of pts with CD8+ infiltrate, worse (p 0.02) OS was
observed for PD-L1(IC)+ cases. Conclusions: Our findings support the hypothesis
that CD8/Tia1 infiltrate in tumor microenvironment at diagnosis confers superior
survival for pts with localized osteosarcoma, while PD-L1 expression is
associated with worse survival.
PMID- 29340097
TI - S-adenosyl-methionine (SAM) alters the transcriptome and methylome and
specifically blocks growth and invasiveness of liver cancer cells.
AB - S-adenosyl methionine (SAM) is a ubiquitous methyl donor that was reported to
have chemo- protective activity against liver cancer, however the molecular
footprint of SAM is unknown. We show here that SAM selectively inhibits growth,
transformation and invasiveness of hepatocellular carcinoma cell lines but not
normal primary liver cells. Analysis of the transcriptome of SAM treated and
untreated liver cancer cell lines HepG2 and SKhep1 and primary liver cells
reveals pathways involved in cancer and metastasis that are upregulated in cancer
cells and are downregulated by SAM. Analysis of the methylome using bisulfite
mapping of captured promoters and enhancers reveals that SAM hyper-methylates and
downregulates genes in pathways of growth and metastasis that are upregulated in
liver cancer cells. Depletion of two SAM downregulated genes STMN1 and TAF15
reduces cellular transformation and invasiveness, providing evidence that SAM
targets are genes important for cancer growth and invasiveness. Taken together
these data provide a molecular rationale for SAM as an anticancer agent.
PMID- 29340098
TI - ICAM-1 regulates macrophage polarization by suppressing MCP-1 expression via miR
124 upregulation.
AB - Intercellular adhesion molecule-1 is the adhesion molecule mediating leukocyte
firm adhesion to endothelial cells, plays a critical role in subsequent leukocyte
transmigration. ICAM-1 is also expressed in other cells including macrophages;
however, the role of this adhesion molecule in mediating macrophage functions
remains enigmatic. We report that ICAM-1 regulates macrophage polarization by
positively modulating miR-124 expression. We found higher expression levels of
monocyte chemotactic protein-1 in lungs of mice lacking ICAM-1. Consistent with
this result, siRNA mediated depletion of ICAM-1 in macrophage resulted in
increased expression levels of MCP-1. Moreover, ICAM-1 controlled miR-124
expression and downregulated MCP-1 mRNA and protein expression by binding of miR
124 to MCP-1 3' untranslated region. ICAM-1 also induced the transcription factor
Sp1 expression, which is important for miR-124 expressing in macrophages.
Furthermore, ICAM-1 depletion led to M1 macrophage polarization, in contrast, miR
124 mimics promoted M2 macrophage polarization. Exogenous administration of miR
124 mimics into the lungs prevented lipopolysaccharide-induced myeloperoxidase
activity in vivo, suggesting that miR-124 is important for dampening acute lung
injury. These results collectively show that adhesion molecule ICAM-1
downregulates MCP-1 expression by controlling Sp1 mediated miR-124 levels, which
in turn regulate M2 macrophage polarization. Targeting ICAM-1 and downstream miR
124 may present a new therapeutic strategy for acute lung injury.
PMID- 29340096
TI - CRISPR/Cas9-mediated reversibly immortalized mouse bone marrow stromal stem cells
(BMSCs) retain multipotent features of mesenchymal stem cells (MSCs).
AB - Mesenchymal stem cells (MSCs) are multipotent non-hematopoietic progenitor cells
that can undergo self-renewal and differentiate into multi-lineages. Bone marrow
stromal stem cells (BMSCs) represent one of the most commonly-used MSCs. In order
to overcome the technical challenge of maintaining primary BMSCs in long-term
culture, here we seek to establish reversibly immortalized mouse BMSCs (imBMSCs).
By exploiting CRISPR/Cas9-based homology-directed-repair (HDR) mechanism, we
target SV40T to mouse Rosa26 locus and efficiently immortalize mouse BMSCs (i.e.,
imBMSCs). We also immortalize BMSCs with retroviral vector SSR #41 and establish
imBMSC41 as a control line. Both imBMSCs and imBMSC41 exhibit long-term
proliferative capability although imBMSC41 cells have a higher proliferation
rate. SV40T mRNA expression is 130% higher in imBMSC41 than that in imBMSCs.
However, FLP expression leads to 86% reduction of SV40T expression in imBMSCs,
compared with 63% in imBMSC41 cells. Quantitative genomic PCR analysis indicates
that the average copy number of SV40T and hygromycin is 1.05 for imBMSCs and 2.07
for imBMSC41, respectively. Moreover, FLP expression removes 92% of SV40T in
imBMSCs at the genome DNA level, compared with 58% of that in imBMSC41 cells,
indicating CRISPR/Cas9 HDR-mediated immortalization of BMSCs can be more
effectively reversed than that of retrovirus-mediated random integrations.
Nonetheless, both imBMSCs and imBMSC41 lines express MSC markers and are highly
responsive to BMP9-induced osteogenic, chondrogenic and adipogenic
differentiation in vitro and in vivo. Thus, the engineered imBMSCs can be used as
a promising alternative source of primary MSCs for basic and translational
research in the fields of MSC biology and regenerative medicine.
PMID- 29340099
TI - A plasma miRNA signature for lung cancer early detection.
AB - The early detection of lung cancer continues to be a major clinical challenge.
Using whole-transcriptome next-generation sequencing to analyze lung tumor and
the matched noncancerous tissues, we previously identified 54 lung cancer
associated microRNAs (miRNAs). The objective of this study was to investigate
whether the miRNAs could be used as plasma biomarkers for lung cancer. We
determined expressions of the lung tumor-miRNAs in plasma of a development cohort
of 180 subjects by using reverse transcription PCR to develop biomarkers. The
development cohort included 92 lung cancer patients and 88 cancer-free smokers.
We validated the biomarkers in a validation cohort of 64 individuals comprising
34 lung cancer patients and 30 cancer-free smokers. Of the 54 miRNAs, 30
displayed a significant different expression level in plasma of the lung cancer
patients vs. cancer-free controls (all P < 0.05). A plasma miRNA signature (miRs
126, 145, 210, and 205-5p) with the best prediction was developed, producing
91.5% sensitivity and 96.2% specificity for lung cancer detection. Diagnostic
performance of the plasma miRNA signature had no association with stage and
histological type of lung tumor, and patients' age, sex, and ethnicity (all p >
0.05). The plasma miRNA signature was reproducibly confirmed in the validation
cohort. The plasma miRNA signature may provide a blood-based assay for diagnosing
lung cancer at the early stage, and thereby reduce the associated mortality and
cost.
PMID- 29340100
TI - The inhibition of cordycepin on cancer stemness in TGF-beta induced chemo
resistant ovarian cancer cell.
AB - Chemotherapy is one of the main approach for ovarian cancer. Cancer stem cells
(CSCs) escape chemotherapy and lead to chemoresistance. We previously
demonstrated that cordycepin (Cd) inhibited metastasis in human ovarian carcinoma
cells, the aim of this study is to investigate the effects of Cd on ovarian
cancer stemness. TGF-beta was used to induce chemoresistance of chemotherapeutic
agent cisplatin in SKOV-3 ovarian cancer cells. After treating with 100 MUM of
Cd, cell viability, the percentage of cancer stem cells, and the levels of matrix
metalloproteinases (MMPs) were decreased in TGF-beta-induced SKOV-3 cells.
Treatment of Cd recovered E-cadherin levels and inhibited vimentin levels while
TGF-beta treatment significantly increased the expression of vimentin and PGC
1alpha, and decreased E-cadherin levels in SKOV-3 cells, indicating that the
action of Cd on cancer stemness may contribute to the regulation of epithelial
mesenchymal transition (EMT). Cd efficiently attenuated chemoresistance caused by
TGF-beta in SKOV-3 cancer stem cells to promote the cytotoxicity of cisplatin.
PMID- 29340101
TI - IGF-1 induces the epithelial-mesenchymal transition via Stat5 in hepatocellular
carcinoma.
AB - It has been reported that the epithelial-mesenchymal transition (EMT) plays an
important role in hepatocellular carcinoma (HCC). However, the relationship
between the insulin-like growth factor-1 (IGF-1) and EMT of HCC was not fully
elucidated. In the present work, we found that the expression of N-cadherin,
Vimentin, Snail1, Snail2, and Twist1 was positively associated with IGF-1R
expression, while E-cadherin expression was negatively associated with IGF-1
expression in human HCC samples. Furthermore, we observed that IGF-1 up-regulated
the expression of N-cadherin, Vimentin, Snail1, Snail2 and Twist1, and down
regulated the expression of E-cadherin. In addition, Stat5 was induced in IGF-1
treated HepG2 and Hep3B cells, and Stat5 inhibition or siRNA significantly
affected IGF-1-induced EMT in HepG2 and Hep3B cells. In conclusion, IGF-1 induces
EMT of HCC via Stat5 signaling pathway. Thus, IGF-1/Stat5 can be recommended as a
potential and novel therapeutic strategy for HCC patients.
PMID- 29340102
TI - The impact of antibiotic usage on the efficacy of chemoimmunotherapy is
contingent on the source of tumor-reactive T cells.
AB - In recent years the combined use of chemotherapy and immunotherapy, collectively
termed chemoimmunotherapy, has emerged as a promising treatment option for
patients with cancer. Antibiotics are commonly used to reduce infection-related
complications in patients undergoing chemotherapy. Intriguingly, accumulating
evidence has implicated gut microbiota as a critical determinant of host
antitumor immune responses, raising the question as to whether the use of broad
spectrum antibiotics would invariably diminish tumor response to
chemoimmunotherapies. We investigated the impact of antibiotics on the
therapeutic outcomes of cyclophosphamide (CTX) chemotherapy and adoptive T-cell
therapy (ACT) where CTX was used as the host-conditioning regimen in mice. We
show that antibiotic prophylaxis dampened the endogenous T cell responses
elicited by CTX, and reduced the efficacy of CTX against B-cell lymphoma. In the
ACT setting, antibiotics administration impaired the therapeutic effects of
adoptively transferred tumor-specific CD4+ T cells in mice with implanted
colorectal tumors. In contrast, long-term antibiotic exposure did not affect the
efficacy of ACT using CD19-targeting chimeric antigen receptor (CAR) T cells in
mice with systemic B-cell lymphoma, although it correlated with prolonged CAR
expression and sustained B-cell aplasia. Our study demonstrates that
chemoimmunotherapies may have variable reliance on intestinal microbiota for T
cell activation and function, and thus have different sensitivities to antibiotic
prophylaxis. These findings may have implications for the judicial use of
antibiotics in cancer patients receiving chemoimmunotherapies.
PMID- 29340103
TI - Anti-neoplastic drugs increase caveolin-1-dependent migration, invasion and
metastasis of cancer cells.
AB - Expression of the scaffolding protein Caveolin-1 (CAV1) enhances migration and
invasion of metastatic cancer cells. Yet, CAV1 also functions as a tumor
suppressor in early stages of cancer, where expression is suppressed by
epigenetic mechanisms. Thus, we sought to identify stimuli/mechanisms that revert
epigenetic CAV1 silencing in cancer cells and evaluate how this affects their
metastatic potential. We reasoned that restricted tissue availability of anti
neoplastic drugs during chemotherapy might expose cancer cells to sub-therapeutic
concentrations, which activate signaling pathways and the expression of CAV1 to
favor the acquisition of more aggressive traits. Here, we used in vitro [2D,
invasion] and in vivo (metastasis) assays, as well as genetic and biochemical
approaches to address this question. Colon and breast cancer cells were
identified where CAV1 levels were low due to epigenetic suppression and could be
reverted by treatment with the methyltransferase inhibitor 5'-azacytidine.
Exposure of these cells to anti-neoplastic drugs for short periods of time (24-48
h) increased CAV1 expression through ROS production and MEK/ERK activation. In
colon cancer cells, increased CAV1 expression enhanced migration and invasion in
vitro via pathways requiring Src-family kinases, as well as Rac-1 activity.
Finally, elevated CAV1 expression in colon cancer cells following exposure in
vitro to sub-cytotoxic drug concentrations increased their metastatic potential
in vivo. Therefore exposure of cancer cells to anti-neoplastic drugs at non
lethal drug concentrations induces signaling events and changes in transcription
that favor CAV1-dependent migration, invasion and metastasis. Importantly, this
may occur in the absence of selection for drug-resistance.
PMID- 29340104
TI - Somatic mutation dynamics in MDS patients treated with azacitidine indicate
clonal selection in patients-responders.
AB - Azacitidine (AZA) for higher risk MDS patients is a standard therapy with limited
durability. To monitor mutation dynamics during AZA therapy we utilized massive
parallel sequencing of 54 genes previously associated with MDS/AML pathogenesis.
Serial sampling before and during AZA therapy of 38 patients (reaching median
overall survival 24 months (Mo) with 60% clinical responses) identified 116
somatic pathogenic variants with allele frequency (VAF) exceeding 5%. High
accuracy of data was achieved via duplicate libraries from myeloid cells and T
cell controls. We observed that nearly half of the variants were stable while
other variants were highly dynamic. Patients with marked decrease of allelic
burden upon AZA therapy achieved clinical responses. In contrast, early
progressing patients on AZA displayed minimal changes of the mutation pattern. We
modeled the VAF dynamics on AZA and utilized a joint model for the overall
survival and response duration. While the presence of certain variants associated
with clinical outcomes, such as the mutations of CDKN2A were adverse predictors
while KDM6A mutations yield lower risk of dying, the data also indicate that
allelic burden volatility represents additional important prognostic variable. In
addition, preceding 5q- syndrome represents strong positive predictor of longer
overall survival and response duration in high risk MDS patients treated with
AZA. In conclusion, variants dynamics detected via serial sampling represents
another parameter to consider when evaluating AZA efficacy and predicting
outcome.
PMID- 29340105
TI - Long-term effects of sitagliptin in patients with type 2 diabetes mellitus and
hypertension: results from the PROLOGUE study.
AB - Background: The effects of sitagliptin in patients with type 2 diabetes mellitus
and hypertension are unclear. Therefore, we evaluated the long-term effects of
sitagliptin in those patients. Methods: In the PROLOGUE study, 365 patients were
diagnosed as type 2 diabetes mellitus and hypertension, and 189 patients in the
sitagliptin group, 176 patients in the conventional group. Fasting blood glucose
(FBG), HbA1c, systolic pressure (SP), diastolic pressure (DP), serum urea
nitrogen (BUN) and serum creatinine (SCR) were measured at the beginning of the
study and after 12 and 24 months of treatment. Results: FBS and HbA1c levels were
not significantly decreased after treatment [12 months: OR: -3.1, 95% CI (-11.3,
5.0); OR: 0.1, 95% CI (0.0, 0.3); 24 months: OR: -0.1, 95% CI (-9.1, 8.8); OR:
0.1, 95% CI (0.0, 0.3), respectively]. BP and DP levels were not significantly
decreased after treatment (12 months: OR: 0.9, 95% CI (-2.8, 4.6); OR: 0.6, 95%
CI (-2.0, 3.2); 24 months: OR: -0.5, 95% CI (-4.2, 3.1); OR: -1.6, 95% CI (-41,
0.9), respectively]. Furthermore, BUN and SCR levels were not significantly
decreased after treatment (12 months: OR: 0.0, 95%CI (-1.2, 1.2); OR: 0.0, 95% CI
(-0.1, 0.0); 24 months: OR: 0.4, 95% CI (-1.0, 1.8); OR: -80.8, 95% CI (-201.3,
39.8), respectively]. After adjusting for confounding factors, our results did
not change. Conclusions: In our study, there was no evidence that treatment with
sitagliptin can improve FBS, BP, DP, BUN or SCR in patients with type 2 diabetes
mellitus and hypertension. Trial Registration: University Hospital Medical
Information Network Clinical Trials Registry UMIN000004490.
PMID- 29340106
TI - A maternal high-fat diet during pregnancy and lactation, in addition to a
postnatal high-fat diet, leads to metabolic syndrome with spatial learning and
memory deficits: beneficial effects of resveratrol.
AB - We tested the hypothesis that high-fat diet consumption during pregnancy,
lactation, and/or post weaning, altered the expression of molecular mediators
involved in hippocampal synaptic efficacy and impaired spatial learning and
memory in adulthood. The beneficial effect of resveratrol was assessed. Dams were
fed a rat chow diet or a high-fat diet before mating, during pregnancy, and
throughout lactation. Offspring were weaned onto either a rat chow or a high-fat
diet. Four experimental groups were generated, namely CC, HC, CH, and HH
(maternal chow diet or high-fat diet; postnatal chow diet or high-fat diet). A
fifth group fed with HH plus resveratrol (HHR) was generated. Morris water maze
test was used to evaluate spatial learning and memory. Blood pressure and IPGTT
was measured to assess insulin resistance. Dorsal hippocampal expression of
certain biochemical molecules, including sirtuin 1, ERK, PPARgamma, adiponectin,
and BDNF were measured. Rats in HH group showed impaired spatial memory, which
was partly restored by the administration of resveratrol. Rats in HH group also
showed impaired glucose tolerance and increased blood pressure, all of which was
rescued by resveratrol administration. Additionally, SIRT1, phospho-ERK1/2, and
phospho-PPARgamma, adiponectin and BDNF were all dysregulated in rats placed in
HH group; administration of resveratrol restored the expression and regulation of
these molecules. Overall, our results suggest that maternal high-fat diet during
pregnancy and/or lactation sensitizes the offspring to the adverse effects of a
subsequent high-fat diet on hippocampal function; however, administration of
resveratrol is demonstrated to be beneficial in rescuing these effects.
PMID- 29340107
TI - A comparison of ARMS-Plus and droplet digital PCR for detecting EGFR activating
mutations in plasma.
AB - In this study, we introduce a novel amplification refractory mutation system
(ARMS)-based assay, namely ARMS-Plus, for the detection of epidermal growth
factor receptor (EGFR) mutations in plasma samples. We evaluated the performance
of ARMS-Plus in comparison with droplet digital PCR (ddPCR) and assessed the
significance of plasma EGFR mutations in predicting efficacy of EGFR-tyrosine
kinase inhibitor (TKI) regimen. A total of 122 advanced non-small cell lung
cancer (NSCLC) patients were enrolled in this study. The tumor tissue samples
from these patients were evaluated by conventional ARMS PCR method to confirm
their EGFR mutation status. For the 116 plasma samples analyzed by ARMS-Plus, the
sensitivity, specificity, and concordance rate were 77.27% (34/44), 97.22%
(70/72), and 89.66% (104/116; kappa=0.77, P<0.0001), respectively. Among the 71
plasma samples analyzed by both ARMS-Plus and ddPCR, ARMS-Plus showed a higher
sensitivity than ddPCR (83.33% versus 70.83%). The presence of EGFR activating
mutations in plasma was not associated with the response to EGFR-TKI, although
further validation with a larger cohort is required to confirm the correlation.
Collectively, the performance of ARMS-Plus and ddPCR are comparable. ARMS-Plus
could be a potential alternative to tissue genotyping for the detection of plasma
EGFR mutations in NSCLC patients.
PMID- 29340108
TI - Effect of gene-lifestyle interaction on gestational diabetes risk.
AB - We hypothesized that the association of certain lifestyle parameters with
gestational diabetes mellitus (GDM) risk would depend on susceptibility loci. In
total, 278 Russian women with GDM and 179 controls completed questionnaires about
lifestyle habits (food consumption, physical activity and smoking). GDM was
diagnosed according to the criteria of the International Association of Diabetes
and Pregnancy Study Groups. Maternal blood was sampled for genotyping single
nucleotide polymorphisms (SNPs) in MTNR1B (rs10830963 and rs1387153), GCK
(rs1799884), KCNJ11 (rs5219), IGF2BP2 (rs4402960), TCF7L2 (rs7903146 and
rs12255372), CDKAL1 (rs7754840), IRS1 (rs1801278) and FTO (rs9939609). Binary
logistic regression revealed an interaction effect of sausage intake and the
number of risk alleles of two SNPs (rs10830963 in MTNR1B and rs1799884 in GCK) on
GDM risk (P < 0.001). Among women without risk alleles of these two SNPs, sausage
consumption was positively associated with GDM risk (P trend = 0.045). This
difference was not revealed in women carrying 1 or more risk alleles. The risk of
GDM increased as the number of risk alles increased in participants with low and
moderate sausage consumption (P trend <0.001 and 0.006, respectively), while the
risk of GDM in women with high sausage consumption remained relatively high,
independent of the number of risk alleles. These findings indicate that the
association of sausage consumption with GDM risk can be determined based on the
number of risk alleles of rs10830963 in MTNR1B and rs1799884 in GCK.
PMID- 29340110
TI - Curcumin attenuates myocardial ischemia-reperfusion injury.
AB - Background: Cardiovascular diseases (CVDs) are at a badly high-risk of morbidity
and mortality in the world. Methods: Our study was attempted to investigate the
cardioprotective role of curcumin. Hearts injury was assessed in isolated hearts
and the rats of coronary artery ligated. Results and Conclusions: The inhibition
of pro-inflammatory cytokines was observed by curcumin in coronary artery ligated
rats. ST segment was also reduced by curcumin. Triphenyltetrazolium chloride
staining (TTC) staining and pathological analysis were also showed that curcumin
could dramatically alleviate myocardial injury. Besides, the results in vitro
also demonstrated that curcumin could improved the function of isolated hearts.
Besides, the expressions of inflammation-related pathway in both rats and
isolated hearts treated with curcumin were significantly decreased. The present
study investigated the protective effects of curcumin on myocardial injury and
its mechanism.
PMID- 29340109
TI - Development of a targeted sequencing approach to identify prognostic, predictive
and diagnostic markers in paediatric solid tumours.
AB - The implementation of personalised medicine in childhood cancers has been limited
by a lack of clinically validated multi-target sequencing approaches specific for
paediatric solid tumours. In order to support innovative clinical trials in high
risk patients with unmet need, we have developed a clinically relevant targeted
sequencing panel spanning 311 kb and comprising 78 genes involved in childhood
cancers. A total of 132 samples were used for the validation of the panel,
including Horizon Discovery cell blends (n=4), cell lines (n=15), formalin-fixed
paraffin embedded (FFPE, n=83) and fresh frozen tissue (FF, n=30) patient
samples. Cell blends containing known single nucleotide variants (SNVs, n=528)
and small insertion-deletions (indels n=108) were used to define panel
sensitivities of >=98% for SNVs and >=83% for indels [95% CI] and panel
specificity of >=98% [95% CI] for SNVs. FFPE samples performed comparably to FF
samples (n=15 paired). Of 95 well-characterised genetic abnormalities in 33
clinical specimens and 13 cell lines (including SNVs, indels, amplifications,
rearrangements and chromosome losses), 94 (98.9%) were detected by our approach.
We have validated a robust and practical methodology to guide clinical management
of children with solid tumours based on their molecular profiles. Our work
demonstrates the value of targeted gene sequencing in the development of
precision medicine strategies in paediatric oncology.
PMID- 29340111
TI - Effect of dihydropyrimidine dehydrogenase single nucleotide polymorphisms on
prognosis of breast cancer patients with chemotherapy.
AB - Defining biomarkers that predict therapeutic effects and adverse events is a
crucial mandate to guide patient selection for personalized cancer treatments.
DPD (dihydropyrimidine dehydrogenase, encoded by DPYD gene) is the initial and
rate-limiting enzyme of metabolic pathway of fluoropyrimidines, and
fluoropyrimidines are common used drug therapies for breast cancer. Previous
studies on DPYD polymorphism were mainly focused on its association with
fluoropyrimidines toxicity. In our present study, 5 DPYD single nucleotide
polymorphisms status was detected from tumor tissues of 331 invasive breast
cancer patients using standard techniques. We for the first time investigated the
prognostic significance of DPYD polymorphisms in breast cancer. We demonstrated
non-luminal breast cancer patients carrying DPYD c.1627A>G AG/GG treated with
fluoropyrimidine-based regimen presented a shorter overall survival and
progression-free survival than carriers treated with non-fluoropyrimidine
regimen. However, non-luminal DPYD c.1627A>G AG/GG carriers treated with TE
(taxane and anthracycline)-based regimen showed a better prognosis compared with
carriers treated with non-TE regimen. Our results suggested TE-based chemotherapy
was a suitable regimen for non-luminal patients with DPYD c.1627A>G AG/GG
genotype and fluoropyrimidine-based regimen should not be recommended for those
patients. Our findings provided a novel strategy, which will guide clinicians to
choose more precise chemotherapy treatment for breast cancer patients.
PMID- 29340112
TI - Incidence and relative risk of peripheral neuropathy in cancer patients treated
with eribulin: a meta-analysis.
AB - Background: Eribulin is a microtubule inhibitor, which is approved for the
treatment of breast cancer. Peripheral neuropathy has been reported in the
studies of eribulin, but the incidence and relative risk (RR) of eribulin
associated peripheral neuropathy varied greatly in cancer patients. The purpose
of this meta-analysis was to determine the overall incidence and RR of eribulin
associated peripheral neuropathy in cancer patients. Materials and Methods:
Pubmed database and Embase and abstracts presented at the American Society of
Clinical Oncology (ASCO) meetings were systematically reviewed for primary
studies. Eligible studies included prospective clinical trials and expanded
access programs of cancer patients treated with eribulin. Statistical analyses
were performed to calculate the incidences, RRs, and 95% confidence intervals
(CIs). Results: Altogether, 4,849 patients from 19 clinical trials were selected
for this meta-analysis. The incidences of all-grade and high-grade peripheral
neuropathy were 27.5% (95% CI: 23.3-32.4%) and 4.7% (95% CI: 3.6-6.2%),
respectively. The relative risks of peripheral neuropathy of eribulin compared to
control were increased for all-grade (RR = 1.89, 95% CI: 1.10-3.25) but not
statistically significant for high-grade (RR = 2.98, 95% CI: 0.71-12.42).
Conclusions: The use of eribulin is associated with an increased incidence of
peripheral neuropathy. The RR is increased for all-grade peripheral neuropathy.
PMID- 29340113
TI - Prognostic role of platelet to lymphocyte ratio in esophageal cancer: A meta
analysis.
AB - Purpose: The prognostic role of inflammation index like platelet to lymphocyte
ratio (PLR) in esophageal cancer remains controversial. We evaluated the
prognostic significance of PLR in esophageal cancer patients. Methods: We
searched databases to identify relevant literatures. Pooled hazard ratios (HRs)
and 95% confidence intervals (CIs) were calculated. A meta-analysis was performed
to evaluate the prognostic value of PLR in patients with esophageal cancer.
Results: A total of 6,699 patients from 16 studies (17 cohorts) were finally
enrolled in the meta-analysis. The results demonstrate that the elevated PLR
predicted poorer overall survival (OS) (HR: 1.389, 95% CI: 1.161-1.663) and
disease-free survival (DFS) (HR: 1.404, 95% CI: 1.169-1.687) and cancer-specific
survival (CSS) (HR: 1.686, 95% CI: 1.146-2.480) in patients with esophageal
cancer. Subgroup analysis revealed that the elevated PLR was also associated with
poor OS in esophageal cancer treated by surgery (HR: 1.492, 95%CI: 1.149-1.938,
P<0.05) and mixed treatment (HR: 1.222, 95%CI: 1.009-1.479, P<0.05). In addition,
PLR Cut-off value<=160 (HR: 1.484, 95%CI: 1.088-2.024, P<0.05) and PLR Cut-off
value>160 (HR: 1.391, 95%CI: 1.161-1.666, P<0.05). Conclusion: This meta-analysis
result suggested that PLR might be a significant predicative biomarker of poor
prognosis for esophageal cancer patients.
PMID- 29340114
TI - Survival benefit evaluation of radiotherapy in esophageal cancer patients aged 80
and older.
AB - Purpose: To evaluate the survival benefit of radiotherapy (RT) in esophageal
cancer (EC) patients aged >= 80. Materials and Methods: Records for all EC
patients aged >= 65 years were extracted from the Surveillance, Epidemiology, and
End Results database. Chi-square test compared the characteristic and treatment
between patients aged >= 80 with those aged 65-79. Focusing on patients aged >=
80, we employed multivariable logistic regression to identify the association
between selection of RT and patients' characteristics. Survival curve was
employed to visualize the survival rate and multivariable Cox proportional hazard
model was established to quantify the effect of RT on overall survival (OS) and
cancer special survival (CSS). Results: Patients aged >= 80 were more likely to
be white male and have localized EC (all P < 0.001). Selection of RT in patients
aged >= 80 were associated with cancer histology (P < 0.001), grade (P = 0.024)
and stage (P < 0.001). RT significantly improved the OS (hazard ratio(HR) =
0.717) and CSS (HR = 0.722) (all P < 0.001). Further stratified analysis found
the improvement were only significant in the localized (OS HR = 0.662; CSS
HR=0.652) and regional stage patients (OS HR = 0.571; CSS HR = 0.581) (all P <
0.001). Conclusions: Our study suggested EC patients aged >= 80 benefit from RT
only if the cancer is in localized/regional stage.
PMID- 29340115
TI - Hypermutation and microsatellite instability in gastrointestinal cancers.
AB - Recent progress in cancer genome analysis using next-generation sequencing has
revealed a high mutation burden in some tumors. The particularly high rate of
somatic mutation in these tumors correlates with the generation of neo-antigens
capable of eliciting an immune response. Identification of hypermutated tumors is
therefore clinically valuable for selecting patients suitable for immunotherapy
treatment. There are several known causes of hypermutation in tumors, such as
ultraviolet light in melanoma, tobacco smoke in lung cancer, and excessive APOBEC
(apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) activity in
breast and gastric cancer. In gastrointestinal cancers, one of the leading causes
of hypermutation is a defect in DNA mismatch repair, which results in
microsatellite instability (MSI). This review will focus on the frequency,
characteristics and genomic signature of hypermutated gastrointestinal cancers
with MSI. Detection of tumor hypermutation in cancer is expected to not only
predict the clinical benefit of immune checkpoint inhibitor treatment, but also
to provide better surgical strategies for the patients with hypermutated tumors.
Thus, in an era of precision medicine, identification of hypermutation and MSI
will play an important role directing surgical and chemotherapeutic treatment.
PMID- 29340116
TI - T follicular helper cells: a potential therapeutic target in follicular lymphoma.
AB - Follicular lymphoma (FL), the most common indolent B-cell non-Hodgkin lymphoma (B
NHL), is a germinal center (GC)-derived lymphoma. The mechanisms underlying B
cell differentiation/maturation in GCs could be also involved in their malignant
transformation. Moreover, the non-malignant cell composition and architecture of
the tumor microenvironment can influence FL development and outcome. Here, we
review recent research advances on CD4 helper T cells in FL that highlight the
pivotal role of T follicular helper (TFH) cells in a complex multicellular system
where they interact with B cells during GC dynamics. After describing the
mechanism of FL lymphomagenesis, we discuss the emerging evidence about TFH cell
enrichment and involvement in FL tumorigenesis and in B-T cell interaction, TFH
regulation by T follicular regulatory cells (TFR) and its potential effect on FL.
Then, we provide an overview on the flexible interplay between the different CD4
T-cell subtypes and how this may be predicted in normal and pathologic contexts,
according to the cell epigenetic state. Finally, we highlight the importance of
targeting TFH cells in the clinic, summarize the main outstanding questions about
TFH and TFR cells in FL, and describe strategies to potentiate FL therapy by
taking into account TFH cells.
PMID- 29340118
TI - Apelin/APJ system: A key therapeutic target for liver disease.
AB - Apelin, a new bioactive peptide, was identified as an endogenous ligand for APJ
(Angiotensin II receptor-like 1). Apelin and its receptor have an abundant
distribution in central nervous system and peripheral tissues, including liver.
Apelin/APJ has diverse physiological and pathological effects, including
regulation of cardiovascular function, angiogenesis, fluid homeostasis and so on.
Apelin/APJ system may act as a novel potential therapeutic target for liver
disease. In this article, we review the role of apelin/APJ system in liver
fibrosis, hepatitis, hepatic cirrhosis, liver injury and metabolic liver disease.
PMID- 29340117
TI - The regulation of pre-metastatic niche formation by neutrophils.
AB - Metastasis is a multistep process requiring tumor cell detachment from the
primary tumor and migration to target organs through the lymphatic or blood
circulatory systems. Specific organs are predisposed to metastases in certain
cancers and the formation of supportive metastatic microenvironment determines
tumor cell homing. Such an environment is provided by a pre-metastatic niche that
is formed through the recruitment of bone marrow-derived myeloid cells, however
the mechanisms of its formation are not fully understood. Recent evidence
suggests that the primary tumor itself modulates the environment of secondary
organs prior to tumor cell dissemination. The contribution of neutrophils to the
formation of the pre-metastatic niche is getting growing attention. Obviously,
neutrophils can affect the development of metastasis in two contradicting ways,
by either stimulation or inhibition of this process, depending on the activation
status. Pro-tumor neutrophils actively support metastasis formation by different
mechanisms, including the formation of pre-metastatic niche, tumor cell
attraction, and the direct support of tumor cell proliferation. Moreover,
suppressive neutrophils, which are the granulocytic arm of MDSC, promote tumor
progression by dampening anti-tumor T cell immunity. On the other hand, anti
tumor neutrophils can inhibit metastasis formation by the cytotoxicity towards
tumor cells in the circulation or at the pre-metastatic site, and even via
stimulation of T cell proliferation. Apparently, the regulation of the pro- or
anti-tumor neutrophil properties has significant implications on metastatic
spread in the host. Here we provide an up to date overview of the different roles
neutrophils play in regulating the metastatic processes.
PMID- 29340120
TI - Effect of Short Hydration on Cisplatin-Induced Nephrotoxicity in Cancer Patients:
A Retrospective Study.
AB - Background: The aim of this study was to evaluate the protective role of short
hydration against nephrotoxicity induced by cisplatin (CDDP). Materials and
Methods: Twenty-two patients (13 men and 9 women) under CDDP therapy were
enrolled in this retrospective study between 2009 and 2014. The CDDP was given in
500 ml of isotonic solution, and before and after CDDP administration, the
patients received 10mEq potassium chloride15% and 1gr magnesium sulfate in 1000
ml isotonic saline. Renal parameters were evaluated on the first day of each
cycle of CDDP therapy. Results: Median cumulative CDDP dose was 465 mg/m2. Based
on renal parameters, the prevalence of CDDP-induced nephrotoxicity (CIN) was
22.7%, while no hypokalemia and hypomagnesemia were observed. Conclusion: Short
hydration accompanied with potassium chloride and magnesium sulfate may decrease
the risk of CIN.
PMID- 29340119
TI - MEF2 signaling and human diseases.
AB - The members of myocyte Enhancer Factor 2 (MEF2) protein family was previously
believed to function in the development of heart and muscle. Recent reports
indicate that they are also closely associated with development and progression
of many human diseases. Although their role in cancer biology is well
established, the molecular mechanisms underlying their action is yet largely
unknown. MEF2 family is closely associated with various signaling pathways,
including Ca2+ signaling, MAP kinase signaling, Wnt signaling, PI3K/Akt
signaling, etc. microRNAs also contribute to regulate the activities of MEF2. In
this review, we summarize the known molecular mechanism by which MEF2 family
contribute to human diseases.
PMID- 29340121
TI - Complications of Transfusion-Dependent beta-Thalassemia Patients in Sistan and
Baluchistan, South-East of Iran.
AB - Background: Thalassemia syndromes are among prevalent hereditary disorders
imposing high expenses on health-care system worldwide and in Iran. Organ failure
represents a life-threatening challenge in transfusion- dependent beta
thalassemia (TDT) patients. The purpose of the present study was to determine the
frequency of organ dysfunctions among TDT patients in Sistan and Baluchistan
province in South-East of Iran. Materials and Methods: Laboratory and clinical
data were extracted from medical records as well as by interviews. Standard
criteria were applied to recognize cardiac, gonadal, endocrine and renal
dysfunctions. The collected data were analyzed using the SPSS statistics software
(Ver.19). Results: A total of 613 TDT patients (54.3% males and 45.7% females)
were included in this study. The mean age of patients was 13.3 +/-7.7 years old.
Cardiac events comprised the most encountered complications (76.4%), following by
hypogonadism (46.8%), parathyroid dysfunction (22%), thyroid abnormalities
(8.3%), diabetes (7.8%) and renal disease (1.8%). Hypogonadism comprised the most
identified complication in patient <15 years old, while the cardiac complications
were the most frequent sequela in patients >15 years old (P<0.01). Conclusion: As
cardiac events are significantly more common among TDT patients, close monitoring
of the heart function is recommended for identifying patients with cardiac
problems.
PMID- 29340122
TI - A Cross-Sectional Study of Glycemic Status and Zinc Level in Patients with Beta
Thalassemia Major.
AB - Background: Endocrinopathies and diabetes mellitus are prevalent in patients with
beta-thalassemia major Recently some studies demonstrate a link between low
levels of serum zinc level and higher prevalence of diabetes. The aim of this
study was to evaluate the glucose tolerance in patients suffered from beta
thalassemia major and determine the association of Homeostasis Model Assessment
(HOMA) parameters with zinc status among these patients. Materials andMethods: In
this cross sectional study, clinical data of patients who were suffered from
thalassemia major, aged>=10 years were collected. Serum ferritin concentration,
fasting blood sugar, fasting blood insulin and serum zinc level were assessed
after overnight fasting. Moreover, oral glucose tolerance test was performed.
Homeostasis Model Assessment (HOMA-2) was used for calculating beta-cell
function, insulin resistance and sensitivity for normoglycemic and pre-diabetic
subjects. Results: of the 163 patients diagnosed with beta-thalassemia major,
10%, 53% and 37% were diabetic, pre-diabetic and normal, respectively. Mean serum
zinc concentration was equal to 18.90+/-10.93ug/dl, and it was not significantly
different across diabetic, pre-diabetic and normal groups. Pre-diabetic patients
had significantly lower beta-cell function compared to normal subjects
(P=0.0001). An inverse relation was documented between beta-cell function on one
hand and total units of blood transfusion and ferritin level on the other hand
(r=-0.29, P=0.004 and r=-0.27, P=0.03, respectively). The analysis adjusted for
multiple possible confounders showed that there is no significant association
between HOMA parameters and serum zinc level. Conclusion: Impaired glucose
metabolism and low serum zinc level were quite common among our study
participants. The findings of the study also signifies the substantial role of
follow-up in early detection and appropriate treatment.
PMID- 29340123
TI - Multiple Extramedullary Plasmacytoma in a Setting of Complete Bone Marrow
Remission: Food for Thought.
AB - Extramedullary plasmacytoma as a mode of relapse in multiple myeloma (MM) is
unusual. Current recommendations do not incorporate the routine use of 18
fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT)
imaging prior to haematopoietic stem cell transplant (HSCT) in MM. We report a
case of relapsed MM with complete remission as per IMWG criteria. In the interim
period, before the HSCT, the patient had localizing neurological signs and
symptoms attributed to multiple extramedullary plasmacytomas. The uniqueness of
this case is that this patient after complete marrow remission with no obvious
external masses had unexpected, symptomatic multiple extramedullary
plasmacytomas. This case illustrates the need for integration of FDG PET/CT
imaging into routine pre-HSCT investigations in relapsed MM to prevent missing
any asymptomatic extramedullary plasmacytomas.
PMID- 29340124
TI - The Use of Filgrastim in Patients with Hodgkin Lymphoma Receiving ABVD.
AB - Background: There is conflicting data about the increased risk of pulmonary
toxicity when granulocyte-stimulating factor (G-CSF) is given in combination with
bleomycin. No clear consensus for management of patients with Hodgkin lymphoma
(HL) who require G-CSF support exists. Our objective was to evaluate whether
there is an increase in pulmonary toxicity in patients who receive bleomycin and
G-CSF during treatment for HL. Materials and Methods: We conducted a single
center retrospective analysis of patients with Hodgkin Lymphoma from January 2003
until July 2015. All patients who received at least 1 dose of bleomycin and
followed at our institution were included. Patients were evaluated for pulmonary
toxicity starting from the day of first dose of bleomycin until 1 year after
initiation of bleomycin. Data on pre-identified risk factors for pulmonary
toxicity were also collected. Results: Fifty-four patients met inclusion
criteria. Twenty-one patients received bleomycin alone, and 33 patients received
bleomycin and G-CSF. There was no statistically significant (p = 0.50) difference
in the development of pulmonary toxicity between the two groups. Crude hazard
ratio for development of pulmonary toxicity in the bleomycin and G-CSF cohort was
1.58 (95% confidence interval, CI: 0.41-6.12). On multivariate analysis, the
hazard ratio for development of pulmonary toxicity was 1.71 (95% CI: 0.43-6.81).
Conclusion: This study does not find evidence that the combination of bleomycin
and G-CSF increases the risk for bleomycin- induced pulmonary toxicity. We
recommend G-CSF use in HL patients receiving bleomycin when needed to maintain
dose intensity.
PMID- 29340125
TI - Rare Presentation of Refractory Thrombotic Thrombocytopenic Purpura: Jejunal
Stricture.
AB - Thrombotic thrombocytopenic purpura is a rare thrombotic disease characterized by
episodes of thrombocytopenia and microangiopathic hemolytic anemia due to
disseminated microvascular thrombosis. Thrombotic thrombocytopenic purpura was
first described in 1924 by Moschowitz as a disease presenting with a pentad of
signs and symptoms (anemia, thrombocytopenia, fever, hemiparesis and hematuria).
Previous studies have described atypical manifestations of thrombotic
thrombocytopenic purpura such as hemolysis, anemia and thrombosis.
PMID- 29340126
TI - Hepatosplenic Gamma Delta T-Cell Lymphoma (HSGDTCL): Two Rare Case Reports from
Western India.
AB - Peripheral T cell lymphomas are a heterogeneous group of post-thymic, mature
lymphoid malignancies, accounting for approximately 10-15% of all non-Hodgkin's
lymphomas. Hepatosplenic T-cell lymphoma (HSGDTCL) is a rare entity, which is
characterized by primary extra nodal disease with typical sinusoidal or sinusal
infiltration of the liver and the spleen, respectively by expression of the T
cell receptor gammadelta chain, and by a number of other frequent
clinicopathologic features, including aggressive course of disease. Secondary
involvement of liver by hematopoietic malignancies is much more common as
compared to primary liver involvement. Primary involvement of liver by non-
Hodgkin's lymphoma (NHL) is documented and mostly DLBCL (diffuse large B cell
lymphoma) type. But, T cell lymphoma primarily arising from liver is very rare.
It occurred commonly in immunocompromised patients and prognosis is very poor.
Here, we present two case reports of Hepatosplenic gamma-delta T-cell lymphoma
(HSGDTCL) and both are immunocompetent patients. Liver biopsy from the mass and
subsequent IHC (immunohistochemistry) were performed for the purpose of
diagnosis, which were positive for LCA (leukocyte common antigen), CD2 and
negative for CD5, CD20 and CD79a. First patient was a 63-year-old female with
hepatitis C virus seropositivity presented with liver mass simulating
hepatocellular carcinoma. Second patient was a 60-year- old male, chronic
alcoholic patient, presented with liver mass and lytic bony lesion in pelvis.
Both patients were managed with conventional CHOP (cyclophosphamide,
hydroxydaunorubicin, vincristine, and prednisolone) and showed complete response
after 4 cycles of chemotherapy. After completion of 6 cycles of chemotherapy,
both patients remained under 6-month surveillance period for any recurrence of
the disease.
PMID- 29340127
TI - Restarting Thalidomide-Dexamethasone Regimen in a Post-Abortive Female with
Multiple Myeloma: Effective Clinical Response Possible.
AB - Nowadays, the prevalence of Multiple Myeloma (MM) seems to have been increasing
among young females. Here, we report that thalidomide is contraindicated in
pregnant women diagnosed with MM and those desirous of subsequent pregnancy. In
this case report, we compared the clinical response of Thalidomide-Dexamethasone
therapy in a post-abortive woman with persistently elevated beta-hCG levels due
to retained products of conception, undergoing hysterectomy later. This case
report underlines the clinical significance of age, the effect of Thalidomide
Dexamethasone therapy even after initial discontinuation and the response to high
beta-hCG levels.
PMID- 29340128
TI - Hematological Reference Intervals for Healthy Iranian Blood Donors.
AB - Background: Development of locally-derived hematological reference intervals is
necessary for improving the quality of health care and clinical trials. However
hematological reference intervals are affected by several variables including
age, gender and environmental factors. Therefore this study was conducted to
determine the gender and age-specific hematological reference intervals of
healthy Iranian blood donors. Materials and Methods: Selected hematological
indices of 394 healthy blood donor volunteers, donating blood at Tehran Blood
Transfusion Center were analyzed. Hematological reference intervals, stratified
by age and gender were compared. The results of current study were also compared
with those of US population. Results: There were significant gender-related
differences for mean values of hematological indices, with males having higher
mean values of RBC, HCG, HCT and MCV than females. While the mean of PLT and MCH
were higher in women. Age-related differences for mean values of RBC and MCH were
also significant. The comparison of reference intervals, stratified by both
gender and age showed that RBC, HGB and HCT values were higher in males than
females in all age groups. But MCH values of females in all age groups and WBC
and PLT counts in females older than 30 years were higher compared to the males
in the same age group. The results of this study showed some similarity with US
population, with narrower intervals. Conclusion: This study suggests that gender
and age-specific, locally derived hematological reference intervals should be
referred to, before interpretation of any laboratory test result.
PMID- 29340129
TI - Protective Isolation for Patients with Haematological Malignancies: A Pilot Study
Investigating Patients' Distress and Use of Time.
AB - Background: Patients with haematological malignancies are often hospitalized in
protective isolation until full neutrophil recovery in order to prevent
infections. This descriptive pilot study evaluate the level of isolation-related
distress and the use of free time in a sample of Italian onco-haematological
patients who were hospitalized in protective isolation. Materials and Methods:
Participants were 18 patients hospitalized in hematologic ward to receive
induction therapy (n=12) or autologous stem cell transplant (n=6). They completed
a self-report questionnaire before discharge. Results: Participants reported a
moderate level of isolation-related distress, anxiety, and boredom: the more the
anxiety and the boredom, the more the distress (r=.77; P<.001), (r=.79; P<.001),
respectively. The activities performed during isolation were: watching TV
(72.2%), reading (55.6%), thinking (33.3%), surfing in Internet or using PC
(33.3%), and playing games or making cross-words (16.7%). Participants who
reported pessimistic thinking had higher isolation-related distress (P=.004) as
well as anxiety (P<.001) and boredom (P=.001). Conclusion: Haematology Units
should support isolated patients in spending their time in recreational
activities, allowing more contacts with immediate relatives and friends,
providing free TV and Wi-Fi connection inside the room. In addition, patients
should have to keep themselves physically active. Isolation-related distress
could also be reduced by providing psychological support.
PMID- 29340130
TI - Mechanism Action of Platelets and Crucial Blood Coagulation Pathways in
Hemostasis.
AB - Blood is considered to be precious because it is the basic necessity for health;
our body needs a steady provision of oxygen, supplied via blood, to reach
billions of tissues and cells. Hematopoiesis is the process that generates blood
cells of all lineages. However, platelets are the smallest blood component
produced from the very large bone marrow cells called megakaryocytes and they
play a fundamental role in thrombosis and hemostasis. Platelets contribute their
hemostatic capacity via adhesion, activation and aggregation, which are triggered
upon tissue injury, and these actions stimulate the coagulation factors and other
mediators to achieve hemostasis. In addition, these coordinated series of events
are the vital biological processes for wound healing phases. The aim of this
review is to summarize and highlight the important pathways involved in achieving
hemostasis that are ruled by platelets. In addition, this review also describes
the mechanism action of platelets, including adhesion, activation, aggregation,
and coagulation, as well as the factors that aid in hemostasis and wound healing.
PMID- 29340131
TI - Acute Myeloid Leukemia-Genetic Alterations and Their Clinical Prognosis.
AB - Acute myeloid leukemia (AML) is a group of hematological diseases, phenotypic and
genetically heterogeneous, characterized by abnormal accumulation of blast cells
in the bone marrows and peripheral blood. Its incidence rate is approximately 1.5
per 100,000 in infants younger than 1 year of age and 25 per 100,000 persons in
octogenarians. Traditionally, cytogenetic markers are used to stratify patients
in three risk categories: favorable, intermediate and unfavorable. However, the
forecast stratification and the treatment decision for patients with normal
karyotype shows difficulties due to the high clinical heterogeneity. The
identification of several genetic mutations additional to classical molecular
markers has been useful in identifying new entities. Nowadays, many different
mutations and epigenetic aberrations have been implicated in the diagnostic,
prognostic and treatment of AML. This review is focused on describing the most
important molecular markers with implications for clinical practice.
PMID- 29340132
TI - Effect of epilepsy on autism symptoms in Angelman syndrome.
AB - Background: Autism spectrum disorder and epilepsy often co-occur; however, the
extent to which the association between autism symptoms and epilepsy is due to
shared aetiology or to the direct effects of seizures is a topic of ongoing
debate. Angelman syndrome (AS) is presented as a suitable disease model to
explore this association. Methods: Data from medical records and questionnaires
were used to examine the association between age of epilepsy onset, autism
symptoms, genetic aberration and communication level. Forty-eight participants
had genetically verified AS (median age 14.5 years; range 1-57 years). A measure
of autism symptoms (the Social Communication Questionnaire; SCQ) was completed
for 38 individuals aged >= 4 years. Genetic cause was subgrouped into deletion
and other genetic aberrations of the 15q11-q13 area. The number of signs used to
communicate (< 20 sign and >= 20 signs) was used as a measure of nonverbal
communication. Results: Mean age of epilepsy onset was 3.0 years (range 3 months
7.8 years). Mean SCQ score for individuals without epilepsy was 13.6 (SD = 6.7)
and with epilepsy 17.0 (SD = 5.6; p = 0.17); 58% used fewer than 20 signs to
communicate. There were no age differences between groups according to presence
of epilepsy, level of nonverbal communication or type of genetic aberration. SCQ
scores were higher in individuals with the deletion than in those with other
genetic aberrations (18.7 vs 10.8 p = 0.008) and higher in the group who used <
20 signs to communicate (19.4 vs 14.1 p = 0.007). Age of epilepsy onset was
correlated with SCQ (r = - 0.61, p < 0.001). Multiple regression showed that age
of seizure onset was significantly related to SCQ score (beta = - 0.90; p =
0.006), even when the type of genetic abnormality was controlled (R2 = 0.53; F =
10.7; p = 0.001). Conclusions: The study provides support for the notion that
seizures themselves contribute more to autism symptoms than expected from the
underlying genetic pathology alone. The study demonstrates how a rare genetic
syndrome such as Angelman syndrome may be used to study the relation between
epilepsy and autism symptomatology.
PMID- 29340133
TI - A regional assessment of white-tailed deer effects on plant invasion.
AB - Herbivores can profoundly influence plant species assembly, including plant
invasion, and resulting community composition. Population increases of native
herbivores, e.g. white-tailed deer (Odocoileus virginianus), combined with
burgeoning plant invasions raise concerns for native plant diversity and forest
regeneration. While individual researchers typically test for the impact of deer
on plant invasion at a few sites, the overarching influence of deer on plant
invasion across regional scales is unclear. We tested the effects of deer on the
abundance and diversity of introduced and native herbaceous and woody plants
across 23 white-tailed deer research sites distributed across the east-central
and north-eastern USA and representing a wide range of deer densities and
invasive plant abundance and identity. Deer access/exclusion or deer population
density did not affect introduced plant richness or community-level abundance.
Native and total plant species richness, abundance (cover and stem density) and
Shannon diversity were lower in deer-access vs. deer-exclusion plots. Among deer
access plots, native species richness, native and total cover, and Shannon
diversity (cover) declined as deer density increased. Deer access increased the
proportion of introduced species cover (but not of species richness or stem
density). As deer density increased, the proportion of introduced species
richness, cover and stem density all increased. Because absolute abundance of
introduced plants was unaffected by deer, the increase in proportion of
introduced plant abundance is likely an indirect effect of deer reducing native
cover. Indicator species analysis revealed that deer access favoured three
introduced plant species, including Alliaria petiolata and Microstegium vimineum,
as well as four native plant species. In contrast, deer exclusion favoured three
introduced plant species, including Lonicera japonica and Rosa multiflora, and 15
native plant species. Overall, native deer reduced community diversity, lowering
native plant richness and abundance, and benefited certain invasive plants,
suggesting pervasive impacts of this keystone herbivore on plant community
composition and ecosystem services in native forests across broad swathes of the
eastern USA.
PMID- 29340134
TI - Does mycorrhizal status alter herbivore-induced changes in whole-plant resource
partitioning?
AB - Both mycorrhizae and herbivore damage cause rapid changes in source-sink dynamics
within a plant. Mycorrhizae create long-term sinks for carbon within the roots
while damage by leaf-chewing herbivores causes temporary whole-plant shifts in
carbon and nitrogen allocation. Thus, induced responses to herbivory might depend
on the presence or absence of mycorrhizae. We examined the effects of mycorrhizal
presence on induced resource partitioning in tomato (Solanum lycopersicon) in
response to cues from a specialist herbivore Manduca sexta. Differences in plant
size, growth and in the concentrations of carbon-based (soluble sugars and
starch) and nitrogen-based (protein and total nitrogen) resources in three tissue
types (apex, stem and roots) were quantified. Both mycorrhizae and simulated
herbivory altered the concentrations of carbon- and nitrogen-based resources.
Mycorrhizae promoted plant growth, altered sugar and starch levels. Simulated
herbivory resulted in lower concentrations of most resources (sugar, starch and
protein) in the rapidly growing apex tissue, while causing an increase in stem
protein. There was only one interactive effect; the effects of simulated
herbivory were much stronger on the sugar concentration in the apex of non
mycorrhizal plants. This clearly demonstrates that both mycorrhizal colonization
and herbivore cues cause shifts in carbon- and nitrogen-based resources and
further shows there is little interference by mycorrhizae on the direction and
magnitude of plant responses to herbivory. Overall, our results suggest that
herbivore cues, regardless of mycorrhizal status, reduce allocation to the
growing apex while inducing protein storage in the stem, a possible mechanism
that could increase the tolerance of plants to damage.
PMID- 29333233
TI - On the primacy and irreducible nature of first-person versus third-person
information.
AB - In this essay, we will support the claim that at the current level of scientific
advancement a) some first-person accounts cannot be reduced to their third-person
neural and psychophysiological correlates and b) that these first-person accounts
are the only information to reckon when it is necessary to analyse qualia
contents. Consequently, for many phenomena, first-person accounts are the only
reliable source of information available and the knowledge of their neural and
psychophysical correlates don't offer any additional information about them.
PMID- 29333234
TI - Case Report: Laparoscopic hepatectomy in an elderly patient with major
comorbidities.
AB - Surgeons have been hesitant to proceed to hepatectomy in elderly patients, due to
the higher rate of comorbidities and the reduced reserves. An 81-year-old male
with hepatocellular carcinoma in the segment VI of the liver and several major
cardiovascular, pulmonary and metabolic comorbid illnesses was referred to our
department for treatment. He underwent transarterial chemoembolization of the
liver tumor and afterwards he underwent laparoscopic resection of the hepatic
segment VI, with an uneventful postoperative course. This case indicates that
laparoscopic liver resections could be applied even to elderly patients with
major comorbidities after optimization of their medical status.
PMID- 29333233
TI - On the primacy and irreducible nature of first-person versus third-person
information.
AB - In this essay, we will support the claim that at the current level of scientific
advancement a) some first-person accounts cannot be reduced to their third-person
neural and psychophysiological correlates and b) that these first-person accounts
are the only information to reckon when it is necessary to analyse qualia
contents. Consequently, for many phenomena, first-person accounts are the only
reliable source of information available and the knowledge of their neural and
psychophysical correlates don't offer any additional information about them.
PMID- 29333235
TI - Case Report: Synchronous primary malignancy including the breast and endometrium.
AB - Breast and endometrial cancer are the most common types of female cancers, but
the incidence of both of these malignancies in a single patient is a rare event.
Multiple primary malignancy has been increasingly reported over the past decade,
and double primary cancer is considered as the most common type. In this study,
we present a 53-year-old woman with synchronous primary malignancy of breast and
endometrium. This patient had a history of breast and endometrial cancer in her
family. Mammography and chest CT of the patient revealed a mass in the right
breast and left supraclavicular region. However, the patient did not want to
initiate treatment. Subsequently, the patient returned with a chief complaint of
persistent abnormal vaginal bleeding. Abdominopelvic CT scan of the patient
revealed a huge soft tissue mass in the pelvic cavity. She underwent
hysterectomy, and pathology revealed endometrioid carcinoma, which had invaded
the full thickness of uterine wall. Since this type of malignancy is rare and
several risk factors are associated with it, it is worth being considered by
clinicians when making decisions about screening or strategy for prevention.
PMID- 29333237
TI - Draft genome of tule elk Cervus canadensis nannodes.
AB - This paper presents the first draft genome of the tule elk ( Cervus elaphus
nannodes), a subspecies native to California that underwent an extreme genetic
bottleneck in the late 1800s. The genome was generated from Illumina HiSeq 3000
whole genome sequencing of four individuals, resulting in the assembly of 2.395
billion base pairs (Gbp) over 602,862 contigs over 500 bp and N50 = 6,885 bp.
This genome provides a resource to facilitate future genomic research on elk and
other cervids.
PMID- 29333236
TI - In silico analysis of natural compounds targeting structural and nonstructural
proteins of chikungunya virus.
AB - Background: Chikungunya fever presents as a high-grade fever during its acute
febrile phase and can be prolonged for months as chronic arthritis in affected
individuals. Currently, there are no effective drugs or vaccines against this
virus. The present study was undertaken to evaluate protein-ligand interactions
of all chikungunya virus (CHIKV) proteins with natural compounds from a MolBase
library in order to identify potential inhibitors of CHIKV. Methods: Virtual
screening of the natural compound library against four non-structural and five
structural proteins of CHIKV was performed. Homology models of the viral proteins
with unknown structures were created and energy minimized by molecular dynamic
simulations. Molecular docking was performed to identify the potential inhibitors
for CHIKV. The absorption, distribution, metabolism and excretion (ADME) toxicity
parameters for the potential inhibitors were predicted for further prioritization
of the compounds. Results: Our analysis predicted three compounds, Catechin-5-O
gallate, Rosmarinic acid and Arjungenin, to interact with CHIKV proteins; two
(Catechin-5-O-gallate and Rosmarinic acid) with capsid protein, and one
(Arjungenin) with the E3. Conclusion: The compounds identified show promise as
potential antivirals, but further in vitro studies are required to test their
efficacy against CHIKV.
PMID- 29333239
TI - The peer review process for awarding funds to international science research
consortia: a qualitative developmental evaluation.
AB - Background: Evaluating applications for multi-national, multi-disciplinary, dual
purpose research consortia is highly complex. There has been little research on
the peer review process for evaluating grant applications and almost none on how
applications for multi-national consortia are reviewed. Overseas development
investments are increasingly being channelled into international science
consortia to generate high-quality research while simultaneously strengthening
multi-disciplinary research capacity. We need a better understanding of how such
decisions are made and their effectiveness. Methods: An award-making institution
planned to fund 10 UK-Africa research consortia. Over two annual rounds, 34 out
of 78 eligible applications were shortlisted and reviewed by at least five
external reviewers before final selections were made by a face-to-face panel. We
used an innovative approach involving structured, overt observations of award
making panel meetings and semi-structured interviews with panel members to
explore how assessment criteria concerning research quality and capacity
strengthening were applied during the peer review process. Data were coded and
analysed using pre-designed matrices which incorporated categories relating to
the assessment criteria. Results: In general the process was rigorous and well
managed. However, lack of clarity about differential weighting of criteria and
variations in the panel's understanding of research capacity strengthening
resulted in some inconsistencies in use of the assessment criteria. Using the
same panel for both rounds had advantages, in that during the second round
consensus was achieved more quickly and the panel had increased focus on
development aspects. Conclusion: Grant assessment panels for such complex
research applications need to have topic- and context-specific expertise. They
must also understand research capacity issues and have a flexible but equitable
and transparent approach. This study has developed and tested an approach for
evaluating the operation of such panels and has generated lessons that can
promote coherence and transparency among grant-makers and ultimately make the
award-making process more effective.
PMID- 29333240
TI - The use of dexmedetomidine and intravenous acetaminophen for the prevention of
postoperative delirium in cardiac surgery patients over 60 years of age: a pilot
study.
AB - Background: Delirium is associated with many negative health outcomes.
Postoperative sedation and opioid administration may contribute to delirium. We
hypothesize that the use of dexmedetomidine and Intravenous acetaminophen (IVA)
may lead to reduced opioid consumption and decreased incidence of postoperative
delirium. This pilot study aims to assess feasibility of using dexmedetomidine
and IVA in cardiac surgical patients, and estimate the effect size for incidence
and duration of delirium. Methods: A total of 12 adult patients >60 years of age
undergoing cardiac surgery were recruited and randomized into 4 groups: Propofol
only (P), Propofol with IVA (P+A), Dexmedetomidine only (D), Dexmedetomidine with
IVA (D+A). Preoperative baseline cognition and postoperative delirium was
assessed daily until discharge. The feasibility was assessed by the number of
patients who completed the study. Results: All patients completed the study
successfully. The total incidence of delirium in the study population was 42%
(5/12): 67% (2/3) in the group P, and 67% (2/3) in the group D, 33% (1/3) in
D+A group and 0%(0/3) P+A group. The incidence of delirium was 17% (1/6) in the
group receiving IVA compared to 67% (4/6) that did not receive IVA. The mean
range of duration of delirium was 0-1 days. One patient expired after surgery,
unrelated to the study protocol. One patient in the D group experienced
hypotension (systolic blood pressure <90 mm of Hg.) Conclusions: The feasibility
of performing a project is ascertained by the study. Patients receiving IVA had
lower incidence of delirium compared to patients not receiving IVA which suggests
that IVA may have a role in reducing the incidence of delirium. A prospective
randomized, placebo-controlled trial will be the next step in investigating the
role of dexmedetomidine and IVA in reducing the incidence of delirium.
PMID- 29333241
TI - Developing data interoperability using standards: A wheat community use case.
AB - In this article, we present a joint effort of the wheat research community, along
with data and ontology experts, to develop wheat data interoperability
guidelines. Interoperability is the ability of two or more systems and devices to
cooperate and exchange data, and interpret that shared information.
Interoperability is a growing concern to the wheat scientific community, and
agriculture in general, as the need to interpret the deluge of data obtained
through high-throughput technologies grows. Agreeing on common data formats,
metadata, and vocabulary standards is an important step to obtain the required
data interoperability level in order to add value by encouraging data sharing,
and subsequently facilitate the extraction of new information from existing and
new datasets. During a period of more than 18 months, the RDA Wheat Data
Interoperability Working Group (WDI-WG) surveyed the wheat research community
about the use of data standards, then discussed and selected a set of
recommendations based on consensual criteria. The recommendations promote
standards for data types identified by the wheat research community as the most
important for the coming years: nucleotide sequence variants, genome annotations,
phenotypes, germplasm data, gene expression experiments, and physical maps. For
each of these data types, the guidelines recommend best practices in terms of use
of data formats, metadata standards and ontologies. In addition to the best
practices, the guidelines provide examples of tools and implementations that are
likely to facilitate the adoption of the recommendations. To maximize the
adoption of the recommendations, the WDI-WG used a community-driven approach that
involved the wheat research community from the start, took into account their
needs and practices, and provided them with a framework to keep the
recommendations up to date. We also report this approach's potential to be
generalizable to other (agricultural) domains.
PMID- 29333243
TI - Unexpected results in Chernozem soil respiration while measuring the effect of a
bio-fertilizer on soil microbial activity.
AB - The number of studies investigating the effect of bio-fertilizers is increasing
because of their importance in sustainable agriculture and environmental quality.
In our experiments, we measured the effect of different fertilizers on soil
respiration. In the present study, we were looking for the cause of unexpected
changes in CO2 values while examining Chernozem soil samples. We concluded that
CO2 oxidizing microbes or methanotrophs may be present in the soil that
periodically consume CO2 . This is unusual for a sample taken from the upper
layer of well-ventilated Chernozem soil with optimal moisture content.
PMID- 29333242
TI - Predictive value of early postoperative IOP and bleb morphology in Mitomycin-C
augmented trabeculectomy.
AB - Background: To determine the predictive value of postoperative bleb morphological
features and intraocular pressure (IOP) on the success rate of trabeculectomy.
Methods: In this prospective interventional case series, we analyzed for one year
80 consecutive primary open angle glaucoma patients who underwent mitomycin
augmented trabeculectomy. Bleb morphology was scored using the Indiana bleb
appearance grading scale (IBAGS). Success was defined as IOP <=15 mmHg at 12
months. We applied a multivariable regression analysis and determined the area
under the receiver operating characteristic curve (AUC). Results: The mean age of
participants was 62+/-12.3 years in the success and 63.2+/-16.3 years in the
failure group (P= 0.430) with equal gender distribution (P=0.911). IOPs on day 1,
7 and 30 were similar in both (P= 0.193, 0.639, and 0.238, respectively.) The AUC
of IOP at day 1, day 7 and 30 for predicting a successful outcome was 0.355,
0.452, and 0.80, respectively. The AUC for bleb morphology parameters of bleb
height, extension, and vascularization, on day 14 were 0.368, 0.408, and 0.549,
respectively. Values for day 30 were 0.428, 0.563, and 0.654. IOP change from day
1 to day 30 was a good predictor of failure (AUC=0.838, 95% CI: 0.704 to 0.971)
with a change of more than 3 mmHg predicting failure with a sensitivity of 82.5%
(95% CI: 68 to 91%) and a specificity of 87.5% (95% CI: 53 to 98%). Conclusions:
IOP on day 30 had a fair to good accuracy while bleb features failed to predict
success except bleb vascularity that had a poor to fair accuracy. An IOP
increase more than 3 mmHg during the first 30 days was a good predictor of
failure.
PMID- 29333244
TI - Infectious pancreatic necrosis virus triggers antiviral immune response in
rainbow trout red blood cells, despite not being infective.
AB - Background: Some fish viruses, such as piscine orthoreovirus and infectious
salmon anemia virus, target red blood cells (RBCs), replicate inside them and
induce an immune response. However, the roles of RBCs in the context of
infectious pancreatic necrosis virus (IPNV) infection have not been studied yet.
Methods: Ex vivo rainbow trout RBCs were obtained from peripheral blood, Ficoll
purified and exposed to IPNV in order to analyze infectivity and immune response
using RT-qPCR, immune fluorescence imaging, flow cytometry and western-blotting
techniques. Results: IPNV could not infect RBCs; however, IPNV increased the
expression of the INF1-related genes ifn-1, pkr and mx genes. Moreover,
conditioned media from IPNV-exposed RBCs conferred protection against IPNV
infection in CHSE-214 fish cell line. Conclusions: Despite not being infected,
rainbow trout RBCs could respond to IPNV with increased expression of antiviral
genes. Fish RBCs could be considered as mediators of the antiviral response and
therefore targets of new strategies against fish viral infections. Further
research is ongoing to completely understand the molecular mechanism that
triggers this antiviral response in rainbow trout RBCs.
PMID- 29333245
TI - The impact of fresh gas flow on wash-in, wash-out time and gas consumption for
sevoflurane and desflurane, comparing two anaesthesia machines, a test-lung
study.
AB - Low-flow anaesthesia is considered beneficial for the patient and the
environment, and it is cost reducing due to reduced anaesthetic gas consumption.
An initial high-flow to saturate the circle system ( wash-in) is desirable from a
clinical point of view. We measured the wash-in and wash-out times (time to
saturate and to eliminate the anaesthetic agent, AA), for sevoflurane and
desflurane, in a test-lung with fixed 3 MAC vaporizer setting at different fresh
gas flow (FGF) and calculated the consumption of AA. We tried to find an optimal
flow rate for speed and gas consumption, comparing two anaesthesia machines
(AMs): Aisys and Flow-i. Time to reach 1 minimal alveolar concentration (MAC)
(wash-in) decreased (p<0.05) at higher flow rates (1 - 2 - 4) but plateaued at 4
4.8 l/min. The consumption of AA was at its lowest around 4-4.8 l/min (optimal
flow) for all but the Aisys /desflurane group. Wash-out times decreased as FGF
increased, until reaching plateau at FGF of 4-6 l/min. Aisys had generally
shorter wash-in times at flow rates < 4 l/min as well as lower consumption of AA.
At higher flow rates there were little difference between the AMs. The "optimal
FGF" for wash-out, elimination of gas from the test-lung and circle system,
plateaued with no increase in speed beyond 6 l/min. A fresh gas flow of 4 l/min.
seems "optimal" taking speed to reach a 1 MAC ET and gas consumption into account
during wash-in with a fixed 3 MAC vaporizer setting, and increasing fresh gas
flow beyond 6 l/min does not seem to confirm major benefit during wash-out.
PMID- 29340148
TI - Reducing unnecessary culturing: a systems approach to evaluating urine culture
ordering and collection practices among nurses in two acute care settings.
AB - Background: Inappropriate ordering and acquisition of urine cultures leads to
unnecessary treatment of asymptomatic bacteriuria (ASB). Treatment of ASB
contributes to antimicrobial resistance particularly among hospital-acquired
organisms. Our objective was to investigate urine culture ordering and collection
practices among nurses to identify key system-level and human factor barriers and
facilitators that affect optimal ordering and collection practices. Methods: We
conducted two focus groups, one with ED nurses and the other with ICU nurses.
Questions were developed using the Systems Engineering Initiative for Patient
Safety (SEIPS) framework. We used iterative categorization (directed content
analysis followed by summative content analysis) to code and analyze the data
both deductively (using SEIPS domains) and inductively (emerging themes).
Results: Factors affecting optimal urine ordering and collection included
barriers at the person, process, and task levels. For ED nurses, barriers
included patient factors, physician communication, reflex culture protocols, the
electronic health record, urinary symptoms, and ED throughput. For ICU nurses,
barriers included physician notification of urinalysis results, personal
protective equipment, collection technique, patient body habitus, and Foley
catheter issues. Conclusions: We identified multiple potential process barriers
to nurse adherence with evidence-based recommendations for ordering and
collecting urine cultures in the ICU and ED. A systems approach to identifying
barriers and facilitators can be useful to design interventions for improving
urine ordering and collection practices.
PMID- 29340149
TI - Acute kidney injury due to multiple Hymenoptera stings-a clinicopathological
study.
AB - Background: Acute kidney injury (AKI) after multiple Hymenoptera stings is well
known but still a rare phenomenon. Methods: We conducted a retrospective study of
the clinicopathological spectrum of AKI due to multiple Hymenoptera stings over
13 years (July 2003-June 2016). Results: A total of 35 patients were diagnosed
with AKI due to multiple Hymenoptera stings. The mean age of the patients was
44.7 +/- 17.4 years and the majority (60%) were men. Haematological and
biochemical laboratory abnormalities included anaemia (97.1%), leucocytosis
(54.3%), hyperkalaemia (68.6%), severe metabolic acidosis (51.4%), hepatic
dysfunction (74.3%), haemolysis (91.4%) and rhabdomyolysis (62.9%). The main
complications included acute respiratory distress syndrome (ARDS) and
encephalopathy in four (11.4%) patients each; gastrointestinal bleeding,
hypertension and panniculitis in two (5.7%) patients each and one (2.9%) patient
each developed intra-abdominal bleeding, stroke and polyserositis. Twenty-nine
(83%) patients required dialysis. Ten (29%) patients died. A higher white blood
cell count (P = 0.05) and the complications of ARDS (P = 0.004) and
encephalopathy (P = 0.004) were associated with mortality. The kidney functions
normalized at 5.5 +/- 2.6 weeks in patients who survived. Kidney biopsy was done
in 13 patients. The predominant lesion was acute tubular necrosis (ATN) with or
without pigmented granular cast in 10 (77%) patients. In four (30.8%) patients,
the kidney biopsy showed severe ATN and in the other six (46.2%), the kidney
biopsy showed features of ATN associated with mild to moderate acute interstitial
nephritis (AIN). In three (23%) patients the histopathological examination
revealed only moderate AIN and these patients were treated with a short course of
steroids. Conclusions: AKI due to multiple Hymenoptera stings is severe and is
associated with high mortality. On renal histology, ATN and AIN are common.
PMID- 29340150
TI - Xylose: absorption, fermentation, and post-absorptive metabolism in the pig.
AB - Xylose, as beta-1,4-linked xylan, makes up much of the hemicellulose in cell
walls of cereal carbohydrates fed to pigs. As inclusion of fibrous ingredients in
swine diets continues to increase, supplementation of carbohydrases, such as
xylanase, is of interest. However, much progress is warranted to achieve
consistent enzyme efficacy, including an improved understanding of the
utilization and energetic contribution of xylanase hydrolysis product (i.e.
xylooligosaccharides or monomeric xylose). This review examines reports on xylose
absorption and metabolism in the pig and identifies gaps in this knowledge that
are essential to understanding the value of carbohydrase hydrolysis products in
the nutrition of the pig. Xylose research in pigs was first reported in 1954,
with only sporadic contributions since. Therefore, this review also discusses
relevant xylose research in other monogastric species, including humans. In both
pigs and poultry, increasing purified D-xylose inclusion generally results in
linear decreases in performance, efficiency, and diet digestibility. However,
supplementation levels studied thus far have ranged from 5% to 40%, while
theoretical xylose release due to xylanase supplementation would be less than 4%.
More than 95% of ingested D-xylose disappears before the terminal ileum but
mechanisms of absorption have yet to be fully elucidated. Some data support the
hypothesis that mechanisms exist to handle low xylose concentrations but become
overwhelmed as luminal concentrations increase. Very little is known about xylose
metabolic utilization in vertebrates but it is well recognized that a large
proportion of dietary xylose appears in the urine and significantly decreases the
metabolizable energy available from the diet. Nevertheless, evidence of labeled D
xylose-1-14C appearing as expired 14CO2 in both humans and guinea pigs suggests
that there is potential, although small, for xylose oxidation. It is yet to be
determined if pigs develop increased xylose metabolic capacity with increased
adaptation time to diets supplemented with xylose or xylanase. Overall, xylose
appears to be poorly utilized by the pig, but it is important to consider that
only one study has been reported which supplemented D-xylose dietary
concentrations lower than 5%. Thus, more comprehensive studies testing xylose
metabolic effects at dietary concentrations more relevant to swine nutrition are
warranted.
PMID- 29340151
TI - Reference values for spirometry in elderly individuals: a cross-sectional study
of different reference equations.
AB - Background: Spirometry is the single most important test for the evaluation of
respiratory function. The results are interpreted by comparing measured data with
predicted values previously obtained from a reference population. Reference
equations for spirometry have been discussed previously. The aim of this study
was to compare reference values based on National Health and Nutrition Assessment
Survey (NHANES III), European Community of Steel and Coal (ECSC), and Global Lung
Initiative (GLI) equations in an elderly sample population. Methods: Subjects
from the Geriatric Study on Health Effects of Air Quality in elder care centres
who met the inclusion criteria were enrolled. Spirometry was performed according
to international guidelines. The forced vital capacity, forced expiratory volume
in 1 s, and FEV1/FVC ratio were reported as percentages of the predicted value,
and the lower limit of normality was calculated. Results: Out of 260 elderly
patients, 69.6% were women; the mean age was 83.0 +/- 6.46 years with an age
range of 65-95 years. The lowest %FVC and %FEV1 values were obtained using the
GLI reference equations. However, when NHANES III equations were used, the
FEV1/FVC ratio was higher than ratios obtained from GLI and ECSC equations. The
prevalence of airway obstruction was highest using ECSC equations, while GLI
equations demonstrated more restrictive defects. Conclusions: The present study
showed meaningful differences in the reference values, and consequently, in the
results obtained using NHANES III, ECSC, and GLI reference equations. The
spirometry interpretation was also influenced by the reference equations used.
PMID- 29340152
TI - Impact of gas emboli and hyperbaric treatment on respiratory function of
loggerhead sea turtles (Caretta caretta).
AB - Fisheries interactions are the most serious threats for sea turtle populations.
Despite the existence of some rescue centres providing post-traumatic care and
rehabilitation, adequate treatment is hampered by the lack of understanding of
the problems incurred while turtles remain entrapped in fishing gears. Recently
it was shown that bycaught loggerhead sea turtles (Caretta caretta) could
experience formation of gas emboli (GE) and develop decompression sickness (DCS)
after trawl and gillnet interaction. This condition could be reversed by
hyperbaric O2 treatment (HBOT). The goal of this study was to assess how GE
alters respiratory function in bycaught turtles before recompression therapy and
measure the improvement after this treatment. Specifically, we assessed the
effect of DCS on breath duration, expiratory and inspiratory flow and tidal
volume (VT), and the effectiveness of HBOT to improve these parameters. HBOT
significantly increased respiratory flows by 32-45% while VT increased by 33-35%
immediately after HBOT. Repeated lung function testing indicated a temporal
increase in both respiratory flow and VT for all bycaught turtles, but the
changes were smaller than those seen immediately following HBOT. The current
study suggests that respiratory function is significantly compromised in bycaught
turtles with GE and that HBOT effectively restores lung function. Lung function
testing may provide a novel means to help diagnose the presence of GE, be used to
assess treatment efficacy, and contribute to sea turtle conservation efforts.
PMID- 29340153
TI - Temporal migration patterns between natal locations of ruby-throated hummingbirds
(Archilochus colubris) and their Gulf Coast stopover site.
AB - Background: Autumn latitudinal migrations generally exhibit one of two different
temporal migration patterns: type 1 where southern populations migrate south
before northern populations, or type 2 where northern populations overtake
southern populations en route. The ruby-throated hummingbird (Archilochus
colubris) is a species with an expansive breeding range, which allows
opportunities to examine variation in the timing of migration. Our objective was
to determine a relationship between natal origin of ruby-throated hummingbirds
and arrival at a Gulf coast stopover site; and if so, what factors, such as
differences in body size across the range as well as the cost of migration, might
drive such a pattern. To carry out our objectives, we captured hummingbirds at a
coastal stopover site during autumn migration, at which time we collected
feathers from juveniles for analysis of hydrogen stable isotopes. Using the
hydrogen stable isotope gradient of precipitation across North America and
published hydrogen isotope values of feathers from populations of breeding ruby
throated hummingbirds, we assigned migrants to probable natal latitudes. Results:
Our results confirm that individuals from across the range (30-50 degrees N)
stopover along the Gulf of Mexico and there is a positive relationship between
arrival day and latitude, suggesting a type 1 migration pattern. We also found no
relationship between fuel load (proxy for migration cost) or fat-free body mass
(proxy for body size) and natal latitude. Conclusions: Our results, coupled with
previous work on the spatial migration patterns of hummingbirds, show a type 1
chain migration pattern. While the mechanisms we tested do not seem to influence
the evolution of migratory patterns, other factors such as resource availability
may play a prominent role in the evolution of this migration system.
PMID- 29340154
TI - The impact of sepsis, delirium, and psychological distress on self-rated
cognitive function in ICU survivors-a prospective cohort study.
AB - Background: Many intensive care unit (ICU) survivors develop psychological
problems and cognitive impairment. The relation between sepsis, delirium, and
later cognitive problems is not fully elucidated, and the impact of psychological
symptoms on cognitive function is poorly studied in ICU survivors. The primary
aim of this study was to examine the relationship between sepsis, ICU delirium,
and later self-rated cognitive function. A second aim was to investigate the
association between psychological problems and self-rated cognitive function 3
months after the ICU stay. Methods: Patients staying more than 24 h at the
general ICU at the Karolinska University Hospital Solna, Stockholm, Sweden, were
screened for delirium with the Confusion Assessment Method-ICU (CAM-ICU) during
their ICU stay. Sepsis incidence and severity were recorded. Three months later,
216 patients received the Cognitive Failures Questionnaire (CFQ), Hospital
Anxiety and Depression Scale (HADS), and Post-Traumatic Stress Symptoms-10 (PTSS
10) questionnaires via postal mail. Results: One hundred twenty-five patients
(60%) responded to all questionnaires. Among respondents, the incidence of severe
sepsis or septic shock was 42%. The overall incidence of delirium was 34%.
Patients with severe sepsis/septic shock had a higher incidence of delirium, with
an odds ratio (OR) of 3.7 (95% confidence interval (CI), 1.7-8.1). Self-rated
cognitive problems 3 months post-ICU were found in 58% of the patients. We did
not find any association between sepsis or delirium and late self-rated cognitive
function. However, there was a correlation between psychological symptoms and
self-rated cognitive function, with the strongest correlation between PTSS-10
scores and CFQ scores (r = 0.53; p < 0.001). Conclusions: ICU delirium is more
common in severely septic/septic shock patients. In our cohort, neither severe
sepsis nor ICU delirium was associated with self-rated cognitive function 3
months after the ICU stay. Ongoing psychological symptoms, particularly post
traumatic stress was associated with worse self-rated cognitive function.
Psychological symptoms need to be taken into account when assessing cognitive
function in ICU survivors.
PMID- 29340155
TI - Preservation of renal function by intensive glycemic control.
AB - : We report the case of a 67-year-old Japanese woman with type 1 diabetes
mellitus. At 47 years of age, her hemoglobin A1c (HbA1c) was 10.0%, and she had
overt nephropathy. The first renal biopsy yielded a diagnosis of diabetic
nephropathy. Intensive glycemic control was initiated and her HbA1c improved to
6.0%. Renal dysfunction showed no progression for 15 years. At 62 years of age, a
second renal biopsy was performed. Glomerular lesions did not show progression
but tubulointerstitial fibrosis and vascular lesions showed progression compared
with the first biopsy. Intensive glycemic control can prevent the progression of
glomerular lesions, but might not be effective for interstitial and vascular
lesions. Learning points: Intensive control of blood glucose can prevent the
progression of glomerular lesions.Intensive control of blood glucose may not be
able to prevent progression of interstitial and vascular lesions.CSII reduces
HbA1c without increasing the risk of hypoglycemia.
PMID- 29340156
TI - Hepatotoxicity in hyperthyroid patient after consecutive methimazole and
propylthiouracil therapies.
AB - : Methimazole (MMI) and propylthiouracil (PTU) are widely used antithyroid drugs
(ATD) that have been approved for the treatment of hyperthyroidism.
Hepatotoxicity may be induced by these drugs, though they exert dissimilar
incidence rates of hepatotoxicity and, possibly, with different underlying
pathogenic mechanisms. We report the case of a 55-year-old woman with no relevant
medical history diagnosed with hyperthyroidism due to Graves' disease, who
developed two episodes of acute hepatitis concurrent with the consecutive
administration of two different ATDs, first MMI and then PTU. Given the
impossibility of administering ATDs, it was decided to perform a total
thyroidectomy because the patient was found to be euthyroid at that point.
Pathological anatomy showed diffuse hyperplasia and a papillary thyroid
microcarcinoma of 2 mm in diameter. Subsequent clinical check-ups were normal.
This case suggests the importance of regular monitoring of liver function for
hyperthyroid patients. Due to the potential severity of this side effect, it is
recommended to determine baseline liver function prior to initiation of
treatment. Learning points: We present a rare case of two acute hepatitis
episodes concurrent with two different consecutive ATD therapies.Our results
highlight the relevance of a liver function monitoring during the treatment with
MMI or PTU.A baseline assessment of the liver function before starting an ATD
treatment should be recommendable.
PMID- 29340157
TI - Hypocalcemia due to 22q11.2 deletion syndrome diagnosed in adulthood.
AB - : Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a genetic syndrome that may
present with hypocalcemia due to primary hypoparathyroidism (PH) at any age. We
report a new diagnosis of 22q11.2DS in a 57-year-old man who presented with
symptomatic hypocalcemia. It is important to consider genetic causes of
hypocalcemia due to PH regardless of age. Learning points: It is important to
discard genetic cause of primary hypoparathyroidism in a patient without
autoimmune disease or prior neck surgery.A new diagnosis of a hereditary disease
has familial implications and needs genetic counselling.It is also important to
discard other syndrome's comorbidities.
PMID- 29340158
TI - Follicular thyroid cancer avid on C-11 Methionine PET/CT.
AB - : A case of follicular thyroid cancer with intense focal Methionine uptake on 11C
Methionine PET/CT is reported here. The use of 11C-Methionine PET in
differentiated thyroid cancer is currently being investigated as a surrogate
tracer compared to the more widely used 18F-FDG PET. This case illustrates the
potential incremental value of this modality, not only in the localizing of
parathyroid adenoma, but also indicating that 11C-Methionine PET might have a
potential of increasing the pretest likelihood of thyroid malignancy in a cold
nodule with highly increased Sestamibi uptake. Learning points: 11C-Methionine
PET/CT and 18F-Fluorocholine PET/CT often visualizes the parathyroid adenoma in
case of negative Tc-99m-MIBI SPECT/CT.A cold nodule in Tc-99m Pertechnetat
thyroid scintigraphy with a negative Sestamibi scintigraphy has a very low
probability of being malignant.However, the pretest likelihood of thyroid cancer
in a cold nodule with increased Sestamibi uptake is low.11C-Methionine PET might
have a potential incremental value in increasing the pretest likelihood of
thyroid malignancy in a cold nodule with highly increased Sestamibi uptake.
PMID- 29340159
TI - Recurrent lactic acidosis and hypoglycemia with inadvertent metformin use: a case
of look-alike pills.
AB - : Metformin is recommended as the first-line agent for the treatment of type 2
diabetes. Although this drug has a generally good safety profile, rare but
potentially serious adverse effects may occur. Metformin-associated lactic
acidosis, although very uncommon, carries a significant risk of mortality. The
relationship between metformin accumulation and lactic acidosis is complex and is
affected by the presence of comorbid conditions such as renal and hepatic
disease. Plasma metformin levels do not reliably correlate with the severity of
lactic acidosis. We present a case of inadvertent metformin overdose in a patient
with both renal failure and hepatic cirrhosis, leading to two episodes of lactic
acidosis and hypoglycemia. The patient was successfully treated with hemodialysis
both times and did not develop any further lactic acidosis or hypoglycemia, after
the identification of metformin tablets accidentally mixed in with his supply of
sevelamer tablets. Early initiation of renal replacement therapy is key in
decreasing lactic acidosis-associated mortality. Learning points: When a toxic
ingestion is suspected, direct visualization of the patient's pills is advised in
order to rule out the possibility of patient- or pharmacist-related medication
errors.Though sending a specimen for determination of the plasma metformin
concentration is important when a metformin-treated patient with diabetes
presents with lactic acidosis, complex relationships exist between metformin
accumulation, hyperlactatemia and acidosis, and the drug may not always be the
precipitating factor.Intermittent hemodialysis is recommended as the first-line
treatment for metformin-associated lactic acidosis (MALA).An investigational
delayed-release form of metformin with reduced systemic absorption may carry a
lower risk for MALA in patients with renal insufficiency, in whom metformin
therapy may presently be contraindicated.
PMID- 29340160
TI - Stereotactic body radiation therapy for the treatment of oligoprogression on
androgen receptor targeted therapy in castration-resistant prostate cancer.
AB - Castration-resistant prostate cancer is an incurable disease. To date, six agents
abiraterone, enzalutamide, docetaxel, cabazitaxel, radium-223 and sipuleucel-T-
have shown clinical efficacy in phase III clinical trials, leading to their FDA
approval. Patients are typically sequenced through most or all of these agents,
and then eventually succumb to their disease. Development of new treatments
remains an unmet need. We report a case of a patient who progressed on
enzalutamide with a single enlarging metastatic lesion, was treated with ablative
stereotactic body radiation therapy while maintaining the same systemic
treatment, who then had durable complete remission. Our findings have important
clinical implications and suggest novel clinical trials for this difficult to
treat disease.
PMID- 29340161
TI - Direct ICE imaging from inside the left atrial appendage during ablation of
persistent atrial fibrillation.
AB - We present the case of a 59-year-old patient with persistent atrial fibrillation,
referred for atrial fibrillation ablation. The procedure was performed with the
help of NAVX 3D mapping system (Saint Jude Medical) and iLAB Ultra ICE Plus
ultrasound imaging catheter (Boston Scientific). The catheter permits cross
sectional images perpendicular to catheter's long axis. From inside left atrial
appendage (LAA) looks trabeculated, due to pectinate muscles running parallel to
each other. The presence of a thrombus was excluded from the appendage. The
contractility of LAA was also assessed using multiple frames recorded on
videotape. Our case demonstrates that LAA's morphology and function can be
directly assessed by intracardiac ultrasound with the probe inserted inside the
appendage.
PMID- 29340162
TI - Iatrogenic myocarditis-biomarkers, cardiovascular MRI and the need for early
diagnosis.
PMID- 29340163
TI - The simplest method to classify CAM lesions.
AB - CAM lesions are now seen as a significant pathology that could cause
osteoarthritis of the hip joint. Currently there is no gold standard for
classifying these lesions. We aim to show a simple method for classifying these
lesions based on shape and position. Using CT 3D reconstruction, 91 preoperative
CT scans from patients who had undergone hip arthroscopy for femoroacetabular
impingement, were reconstructed to produce 3D images. Two senior hip surgeons
have devised a simple four type classification system from previous experience.
The system highlights the position and shape of different CAM lesions present in
patients. The two senior surgeons and one junior surgeon reviewed the scans
individually to assess whether the system could be used at all levels of surgical
experience. The two senior surgeons agreed on which type of CAM lesion was
present in all 91 cases. Intra observer reliability scores for the senior
surgeons were 0.90 and 0.91. The junior surgeon reviewed the scans and disagreed
on eight cases. This gave a Kappa co-efficient score of 0.87, which confirms a
reliable system. We believe this classification system is simple and
reproducible. It will aid surgeons in pre and intra-operative management of CAM
lesions. Surgeons will be able to select the optimal portal placement and resect
less capsule depending on the exact CAM lesion identified. This will potentially
reduce complications and improve outcomes in junior hip arthroscopy surgeons.
PMID- 29340164
TI - The 'Hip Vacuum Sign'-a new radiographic phenomenon in femoro-acetabular
impingement.
AB - Femoro-acetabular impingement (FAI) is a frequent cause for groin pain in young
and active patients. We discovered a so far undescribed radiographic phenomenon
only visible in frog-leg lateral radiographs. The aim of this study was to
describe this new radiological sign, to determine its prevalence in a symptomatic
population and to investigate the correlation to a potential underlying
pathology. We retrospectively reviewed all patients, who had been sent to our
clinic between 2010 and 2012 for hip complaints. We excluded patients older than
50 years and patients with advanced osteoarthritis. Two independent investigators
blinded to clinical data independently examined all images for the presence,
location and dimension of a vacuum phenomenon and a potential underlying hip
pathology. We included 242 patients. 137 of them showed clinical and radiological
signs of FAI. A hip vacuum phenomenon was identified in 20 of 242 patients (8%).
Interestingly, all these patients showed distinct signs of femoro-acetabular
impingement. In reference to this, the prevalence of the "Hip Vacuum Sign" was
15% (20/137) in symptomatic patients with FAI. There was no correlation with age
or gender. We identified a new radiological sign, the "Hip Vacuum Sign", in 15%
of symptomatic patients with FAI. It was only visible in frog-leg lateral
radiographs. We suggest that it represents a subluxation of the femoral head due
to a lever mechanism between the femoral neck and the acetabular rim and is,
therefore, a hint for a relevant femoro-acetabular impingement mechanism.
PMID- 29340165
TI - Nitric oxide induced by Indian ginseng root extract inhibits Infectious Bursal
Disease virus in chicken embryo fibroblasts in vitro.
AB - Infectious Bursal Disease is a severe viral disease of chicken responsible for
serious economic losses to poultry farmers. The causative agent, Infectious
Bursal Disease virus, is inhibited by nitric oxide. Root extract of the Indian
ginseng, Withania somnifera, inhibits Infectious Bursal Disease virus in vitro.
Also, Withania somnifera root extract is known to induce nitric oxide production
in vitro. Therefore, the present study was undertaken to determine if the
inhibitory activity of Withania somnifera against Infectious Bursal Disease virus
was based on the production of nitric oxide. We show that besides other
mechanisms, the inhibition of Infectious Bursal Disease virus by Withania
somnifera involves the production of nitric oxide. Our results also highlight the
paradoxical role of nitric oxide in the pathogenesis of Infectious Bursal
Disease.
PMID- 29340166
TI - Withdrawal of antihypertensive therapy in people with dementia: feasibility
study.
AB - Background: This study explored the feasibility of a randomised controlled
withdrawal trial of antihypertensive medication in normotensive people with
dementia. Feasibility aspects included response, recruitment, exclusion and drop
out rates, suitability of outcome measures, acceptability of study procedures and
an indicative economic evaluation for a randomised controlled trial. Methods: A
cohort study attempting the withdrawal of antihypertensive drugs where
appropriate and a feasibility study of home-based blood pressure monitoring, in
people with dementia treated for hypertension, was undertaken. Interviews with
participants and carers and an indicative economic evaluation were also
undertaken. Results: Three hundred and sixty-two primary care practices in the
East Midlands were contacted of which only 41 (11% (95%CI 8-15%)) agreed to
support the study. These 41 practices posted 940 letters to potential
participants. Thirty participants were enrolled in the cohort study of whom 9
were eligible for the antihypertensive withdrawal programme, 20 participated in a
home blood pressure monitoring sub-group analysis and 12 took part in an
interview study. Twenty-two of those enrolled in the cohort study were followed
up at 6 months. The withdrawal programme was acceptable to participants and
general practitioners (GPs). The study procedures including assessments and home
blood pressure monitoring were acceptable to the participants and their carers.
The economic evaluation was not possible. Conclusion: A withdrawal trial of
antihypertensive medication in normotensive people with dementia may not be
feasible in the UK because of low recruitment rates.
PMID- 29340167
TI - Subcutaneous glucagon infusion and continuous glucose monitoring enable effective
management of hypoglycemia in a patient with IGF-2-producing hemangiopericytoma.
AB - Background: Ectopic insulin-like growth factor (IGF)-2 production is a rare
complication of an array of epithelial and mesenchymal tumors, and can clinically
manifest as life-threatening hypoglycemia. Case presentation: A 49-year-old woman
with 13-year history of metastatic hemangiopericytoma, previously treated with
multiple rounds of chemotherapy and palliative radiation, presented to the
emergency department after a hypoglycemic seizure. On arrival, glucose was 18
mg/dL (1.0 mmol/L) and required continuous dextrose infusion for maintenance
within normal limits. Insulin was <2.0 MUU/mL, C-peptide 0.1 ng/mL, and beta
hydroxybutyrate <0.2 mmol/L. Random cortisol was 21 MUg/dL; sulfonylurea screen,
and insulin antibodies were negative. IGF-2 level was 1320 ng/mL; IGF-1 was
within normal limits and IGF binding protein (BP)-3 suppressed. Dexamethasone,
started at 6 mg twice daily, allowed discontinuation of the glucose infusion.
Given concern for nocturnal hypoglycemia, and patient interest in steroid-sparing
anti-hypoglycemic regimen, she was also started on overnight continuous
subcutaneous glucagon infusion via insulin pump. She was discharged with
instructions to maintain a diet high in complex carbohydrates during the day,
while utilizing glucagon pump at night. She was also started on continuous
glucose monitoring system (CGMS) with an alarm to warn of hypoglycemia. Glucagon
infusion rate was later titrated based on CGMS readings. Abdominal CT revealed
increasing size of a right upper quadrant mass not previously subjected to
radiotherapy. After radiation to this area, hypoglycemia improved, allowing
further glucagon titration. In parallel, IGF-2 level declined to 380 ng/mL.
Conclusions: Ectopic IGF-2 production is a rare but often fatal complication of
many cancers, and should be considered on the differential diagnosis in patients
with malignancy and unexplained hypoglycemia. Once hypoglycemia is diagnosed,
patients often have end-stage disease. While treatment of the causative tumor is
the only definitive intervention, anti-hypoglycemia therapy is a life-saving,
temporizing measure. In this case, the patient attained euglycemia and survived 3
months after presentation before ultimately succumbing to other malignancy
related complications. Given efficacy in management of hypoglycemia while
awaiting definitive tumor-directed therapy, we submit nighttime subcutaneous
glucagon infusion and CGMS are valuable additions to the physician's
armamentarium in managing this condition.
PMID- 29340168
TI - Evolution of the vertebrate neurocranium: problems of the premandibular domain
and the origin of the trabecula.
AB - The subdivision of the gnathostome neurocranium into an anterior neural crest
derived moiety and a posterior mesodermal moiety has attracted the interest of
researchers for nearly two centuries. We present a synthetic scenario for the
evolution of this structure, uniting developmental data from living cyclostomes
and gnathostomes with morphological data from fossil stem gnathostomes in a
common phylogenetic framework. Ancestrally, vertebrates had an anteroposteriorly
short forebrain, and the neurocranium was essentially mesodermal; skeletal
structures derived from premandibular ectomesenchyme were mostly anterior to the
brain and formed part of the visceral arch skeleton. The evolution of a one-piece
neurocranial 'head shield' in jawless stem gnathostomes, such as galeaspids and
osteostracans, caused this mesenchyme to become incorporated into the
neurocranium, but its position relative to the brain and nasohypophyseal duct
remained unchanged. Basically similar distribution of the premandibular
ectomesenchyme is inferred, even in placoderms, the earliest jawed vertebrates,
in which the separation of hypophyseal and nasal placodes obliterated the
nasohypophyseal duct, leading to redeployment of this ectomesenchyme between the
separate placodes and permitting differentiation of the crown gnathostome
trabecula that floored the forebrain. Initially this region was very short, and
the bulk of the premandibular cranial part projected anteroventral to the nasal
capsule, as in jawless stem gnathostomes. Due to the lengthening of the
forebrain, the anteriorly projecting 'upper lip' was lost, resulting in the
modern gnathostome neurocranium with a long forebrain cavity floored by the
trabeculae.
PMID- 29340169
TI - Autoimmune retinopathy: A Review.
AB - Autoimmune retinopathy (AIR) is a rare and still poorly understood immune
mediated disease that may cause inflammation from circulating autoantibodies
against the retina. It may be related to history of autoimmune disease in the
patient or in a family member or the presence of neoplastic disease in the
individual. The disease may be subdivided into paraneoplastic and non
paraneoplastic AIR. When related to melanoma, it is referred to as MAR, and when
related to other cancers, it is called CAR. The exact prevalence of AIR is
unknown. It mainly affects older adults. Patients present with bilateral and
asymmetric scotomas, photopsias, visual field defects, with rapidly progressive
visual loss in late onset. In the initial stage, fundus examination is
unremarkable, and in late stages, there is limited retinal epitheliopathy and
vascular attenuation, with or without optic disc pallor, associated or not with
intraocular inflammation and with no evidence of degenerative retinal disease. A
clinical investigation with detailed anamnesis and laboratory tests should be
performed to search for an associated neoplasm. Ophthalmologic and complementary
examinations such as full-field electroretinogram, optical coherence tomography,
visual field and fundus autofluorescence, help the diagnosis. Blood tests to
search for autoantibodies should be requested. Management consists of prolonged
immunosuppression, which may be combined with antioxidant vitamins. In general,
the prognosis is uncertain, so the disease still needs to be better understood.
More studies should be performed to improve diagnostic measures and define
specific management that could preserve or even restore vision.
PMID- 29340170
TI - From a national to an international journal: a new opportunity for the
physiotherapy community.
PMID- 29340171
TI - Passive standing as an adjunct rehabilitation intervention after stroke: a
randomized controlled trial.
AB - Background: Early physical rehabilitation enhances functional recovery in stroke
survivors. Supported standing is a common adjunctive therapeutic practice in
subjects with several central nervous diseases who are unable to stand actively.
Data on the effect of supported positioning on standing frames in individuals
with recent stroke are scarce and contradictory. Objectives: To verify if the
addition of supported standing practice (SSP), delivered by means of a standing
frame in two durations, to conventional physical therapy (CPT), may improve motor
function, autonomy, and mobility in individuals with disability due to recent
stroke. Methods: After baseline assessment, 75 participants with severe
disability due to stroke, all receiving CPT, were randomly assigned to adjunctive
20 or 40 min of SSP, or CPT only (control). Motor function, autonomy, and
mobility were assessed before and after training, and three months later.
Results: All participants assessed received the planned dose of intervention. No
adverse events of SSP were detected. Most outcome measures improved from baseline
through the end of treatment and in the follow-up in all groups; the extent of
change was comparable across the three randomization groups. Conclusions: In this
randomized trial, SSP was unable to provide any sizeable adjunctive benefit,
above and beyond CPT, in subjects with recent stroke.
PMID- 29340172
TI - Can experienced physiotherapists identify which patients are likely to succeed
with physical therapy treatment?
AB - Background: The purpose of the study was to determine if clinician predicted
prognosis is associated with patient outcomes. Methods: The study was a secondary
analysis of data that were collected in 8 physiotherapy outpatient clinics. Nine
physiotherapists with post-graduate training in manual therapy (mean 20.3 years
of experience) were asked at baseline to project the outcome of the patients
evaluated. In total, 112 patients with low back (74 %) or neck (26 %) pain were
treated pragmatically with interventions consisting of manual therapy,
strengthening, and patient-specific education. Outcomes measures consisted of
percent change in disability (Oswestry or Neck Disability Index), self-reported
rate of recovery (0-100 %), and percent change in pain (numerical pain rating
scale). Hierarchical logistic regression determined potential factors (clinician
predicted prognosis score (1-10) at baseline, dichotomised as poor (1-6) and good
(7-10); symptom duration categorised as acute, subacute or chronic; same previous
injury (yes/no); baseline pain and disability scores; within-session improvement
at initial visit (yes/no); and presence of >= one psychological factor)
associated with meaningful changes in each of the three outcomes at discharge
(disability and pain > 50 % improvement, rate of recovery >=82.5 % improvement).
Results: Clinician predicted prognosis (OR 4.15, 95%CI = 1.31, 13.19, p = 0.02)
and duration of symptoms (OR subacute 0.24, 95%CI = 0.07, 0.89, p = 0.03; chronic
0.21, 95%CI = 0.05, 0.90, p = 0.04) were associated with rate of recovery,
whereas only clinician predicted prognosis was associated with disability
improvement (OR 4.28, 95 % CI 1.37, 13.37, p = 0.01). No variables were
associated with pain improvement. Conclusions: Clinician predicted prognosis is
potentially valuable for patients, as a good predicted prognosis is associated
with improvements in disability and rate of recovery.
PMID- 29340173
TI - Scoliosis: lower limb asymmetries during the gait cycle.
AB - Background: Several studies indicate that the gait pattern of subjects suffering
from scoliosis differs from the norm. However, there is conflicting evidence
regarding the source of this discrepancy. Objective: To evaluate lower limb
asymmetries in selected gait variables. Study design: A case-control study on
lower limb asymmetries during gait which can be related to scoliosis. Methods: 31
subjects with scoliosis (Study Group - SG) and an equal comparative control
sample (Control Group - CG) of subjects underwent objective gait analysis with
the Vicon(r) motion caption system whilst walking at a comfortable speed along
the gait laboratory walkway. Analysis was performed at three levels: (1)
Asymmetry in the SG against asymmetry in the CG, (2) Difference in magnitude of
asymmetry between the SG and CG, and (3) Global mean values in the SG vs. CG. The
Paired Student T-Test was used for intra-group analysis whilst the Independent
Student T-Test was used for inter-group analysis of the selected parameters,
which include temporal parameters (stride length, stride time, step length,
individual step speed, speed of gait, cadence, swing-to-stance ratio), ground
reaction force (peak GRF values during Loading and Propulsion phases, vertical
component only) and electromyography (peak EMG values and their time of onset, as
a percentage of the gait cycle) of two lower limb muscles (Gastronemius and
Vastus Medialis). Results: No intra-group variation was found to be significant.
However, the speed of gait was found to be significantly slower (p = 0.03) in
scoliotic subjects when compared to the norm, as a result of the shorter stride
length (p = 0.002 and longer stride time (p = 0.001) in the SG. Furthermore,
there was statistical significance in the time of onset of EMG peaks for the
Lateral Gastrocnemius (p = 0.02) with regards to inter-group difference in
magnitude of lower limb asymmetry and global mean values. Conclusions: Scoliosis
is a tri-planar deformity which has some impact on the gait pattern. This
research study concludes that scoliotic subjects have a slower speed of gait due
to a shorter stride length and a longer stride time, together with variations in
the timing of muscle activation.
PMID- 29340174
TI - Daily functional electrical stimulation during everyday walking activities
improves performance and satisfaction in children with unilateral spastic
cerebral palsy: a randomized controlled trial.
AB - Background: The aim of this paper is to determine whether daily functional
electrical stimulation (FES) is effective in improving self-perceptions of
individually identified mobility performance problems in children with unilateral
spastic cerebral palsy (USCP). We hypothesized that children receiving 8 weeks of
FES treatment would have higher scores for self-perceived performance and
satisfaction on the Canadian Occupational Performance Measure (COPM) for
individually identified priorities than children not receiving FES. Methods:
Thirty-two children (mean age 10 y 8 mo SD 3y 3mo) with USCP and a Gross Motor
Function Classification System I or II were randomly assigned to the FES
treatment group (8 weeks of daily FES) and control group (usual treatments).
Participants were assessed at baseline (week 0), post treatment (week 8) and 6
weeks follow-up (week 14). The primary outcome measures were self-perceived
scores for performance and satisfaction of child- and parent-identified
priorities assessed using the COPM post treatment and at follow-up. The secondary
outcome measures were the categorization of the performance problems from the
COPM and self-report responses according to the International Classification of
Functioning Child and Youth version (ICF-CY). This was clinically important
because an understanding of mobility performance problems for children with USCP
is needed for family-centred service planning. Results: Performance scores (mean
difference 1.6, 95 % CI 0.1 to 3.2, p = 0.034) and satisfaction scores post
treatment (mean difference 2.4, 95 % CI 0.5 to 4.2, p = 0.004) were significantly
higher in the treatment group than in the control group. There were no
significant differences between the groups for performance scores at follow up,
however there was a significant difference between the groups for satisfaction
(mean difference 1.9, 95 % CI 0.1 to 3.8, p = 0.03) in favour of the treatment
group. Priorities were identified across all levels of the ICF-CY but were most
commonly identified in the activity and participation domains of the ICF-CY (79.5
%). Conclusions: Daily FES applied during everyday walking is effective in
addressing self-perceptions of individually identified priorities by improving
the performance and satisfaction of functional skills after treatment. Trial
registration: Australian New Zealand Clinical Trials Register
ACTRN12614000949684. Registered 4 September 2014.
PMID- 29340175
TI - Proprioceptive Based Training for stroke recovery. Proposal of new treatment
modality for rehabilitation of upper limb in neurological diseases.
AB - Background: The central nervous system (CNS) has plastic properties allowing its
adaptation through development. These properties are still maintained in the
adult age and potentially activated in case of brain lesion. In the present study
authors hypothesized that a significant recovery of voluntary muscle contraction
in post stroke patients experiencing severe upper limb paresis can be obtained,
when proprioceptive based stimulations are provided. Proprioceptive based
training (PBT) is based on performing concurrent movements with both unaffected
and affected arm, with the aim to foster motor recovery through some mutual
connections of interhemispheric and transcallosal pathways. The aim of this pre
post pilot study was to evaluate the feasibility of PBT on recovery of voluntary
muscle contraction in subacute phase after stroke. Methods: The treatment lasted
1 h daily, 5 days per week for 3 weeks. The PBT consisted of multidirectional
exercises executed synchronously with unaffected limb and verbal feedback. The
Medical Research Council scale (MRC), Dynamometer, Fugl-Meyer Upper Extremity
scale (F-M UE), Functional Independence Measure scale (FIM) and modified Ashworth
scale were administered at the beginning and at the end of training. Statistical
significance was set at p < 0.05. Results: Six patients with severe paresis of
the upper limb within 6 months after stroke were enrolled in the study (5
ischemic and 1 hemorrhagic stroke, 3 men and 3 women, mean age 65.7 +/- 8.7
years, mean distance from stroke 4.1 +/- 1.5 months) and all of them well
tolerated the training. The clinical changes of voluntary muscle contraction
after PBT were statistically significant at the MRC scale overall (p = 0.028),
and dynamometer assessment overall (p = 0.028). Each patient improved muscle
contraction of one or more muscles and in 4 out of 6 patients voluntary active
movement emerged after therapy. The functional outcomes (i.e. F-M UE and FIM) did
not show significant change within group. Conclusions: The findings of this
preliminary research revealed that PBT may be a feasible intervention to improve
the motricity of upper limb in stroke survivors.
PMID- 29340176
TI - To sit or stand? A preliminary, cross sectional study to investigate if there is
a difference in glenohumeral subluxation in sitting or standing in people
following stroke.
AB - Background: Glenohumeral subluxation (GHS) is a common symptom following stroke.
Many therapists postulate that GHS may be reduced if the base of support (BOS) is
reduced and the centre of mass (COM) is raised as this requires greater postural
muscle activity. However, there is little empirical evidence to support this
practice. Objective: The aim of this preliminary study was to investigate if the
amount of GHS alters from sitting to standing. Study design: A cross sectional,
within-subject design in a convenience sample of 15 stroke patients with GHS was
utilised. Methods: A prospective design was used with a single blinded tester who
assessed GHS using the calliper method in sitting, standing and on return to
sitting. Friedman and post hoc Wilcoxon tests showed that GHS was significantly
reduced in standing compared to sitting (p <0.05) but this reduction was not
maintained on return to sitting (p = 0.25). Conclusions: The results of this
study are limited by its small size. However, these results indicate that
reducing BOS during rehabilitation may improve GHS after stroke. Whilst the
maintenance of benefit is not established, these findings suggest that reducing
BOS as part of treatment may help patients with GHS. Further research is now
required to replicate these results in a larger sample and to directly examine
shoulder muscle activity to investigate which muscles may influence GHS in
response to changing BOS. Future work could also aim to determine whether the
reduction in GHS was directly attributable to a reduced BOS or the effort
associated with moving from sitting to standing.
PMID- 29340177
TI - Finite helical axis for the analysis of joint kinematics: comparison of an
electromagnetic and an optical motion capture system.
AB - Background: The analysis of joints kinematics is important in clinical practice
and in research. Nowadays it is possible to evaluate the mobility of joints in
vivo with different motion capture techniques available in the market. Optical
systems use infrared cameras and reflective markers to evaluate body movements,
while other systems use electromagnetic fields to detect position and orientation
of sensors. The aim of this study was the evaluation of two motion capture
systems based on different technologies (optical and electromagnetic) by
comparing the distribution of finite helical axis (FHA) of rotation during
controlled rotations of an object in different positions. Methods: The
distribution of position and angle errors of the FHA were extracted by optical
and electromagnetic system recordings during a controlled rotation of a low
friction stool in different positions in a controlled environment. Results: The
optical motion capture system showed lower angle and position errors in the
distribution of FHA while the electromagnetic system had higher errors that
increased with increasing distance from the antenna. Conclusions: The optical
system showed lower errors in the estimation of FHA that could make it preferable
with respect to electromagnetic systems during joint kinematics.
PMID- 29340178
TI - Factors associated with citation rate of randomised controlled trials in
physiotherapy.
AB - Background: Despite the use of citation rate as a measure of quality of research
is strongly criticized and debated, it remain a widely used method to evaluate
performances of researchers, articles and journals. The aim of this study was to
test which factors are associated with citation rate of Randomised Controlled
Trials (RCTs) published on the physiotherapy field. Methods: All RCTs abstracted
in the Physiotherapy Evidence Database (PEDro), indexed in Scopus database and
published in 2008 were included. PEDro score, language of publication, indexing
in PubMed database, type of access to articles, subdiscipline, the number of
authors, the country where the study was performed, the type of institution where
the study was conducted and the number of centres involved in the study
(multicentric vs single-centre). and the 2013 5-year impact factor of the
publishing journals were considered as independent variables. Citation rate until
December 2013 was extracted from Scopus database and used as dependent variable.
Results: Six hundred and nineteen RCTs, published in 283 journals, were included
and analysed. The 5-year impact factor was the strongest variable associated with
the citation rate and explained approximately 50 % of the variance, and the
number of authors explained an additional small part (about 1 %) of variability.
The other variables were excluded from the model. Conclusions: The study
highlights that 5-year Impact Factor, not accessibility (language of publication,
indexing in PubMed database or the type of access to articles) or reported
quality (PEDro score), is a strong predictor of the number of citations for RCTs
in the physiotherapy field. Our findings support the increasingly widespread idea
that citation analysis does not reflect the scientific merit of the cited work,
at least in terms of reported quality.The results of this study need to be
confirmed with a publication window larger than one year.
PMID- 29340179
TI - Comparative efficacy of three active treatment modules on psychosocial variables
in patients with long-term mechanical low-back pain: a randomized-controlled
trial.
AB - Background: Psychosocial factors precipitate and perpetuate the risk of
developing long-term Low-Back Pain (LBP) with resultant disability. However,
management of psychosocial aspects of LBP still remains a major challenge. This
study investigated the effect of static or dynamic back extensors endurance
exercise on psychosocial variables of Fear-Avoidance Behaviour (FAB), Pain Self
Efficacy Belief (PSEB) and Back Pain Consequences Belief (BPCB) in patients with
LBP. Methods: A randomized-controlled trial of 67 patients assigned into McKenzie
Protocol (MP) group (n = 25), MP and Static Endurance Exercise Group (MPSEEG; n =
22); and MP and Dynamic Endurance Exercise Group (MPDEEG; n = 20) was carried
out. Treatment was applied thrice weekly for eight weeks. Results: The groups
were comparable in general and baseline psychosocial parameters (p > 0.05). The
different regimens had significant effects on all outcome parameters across
baseline, 4th and 8th week (p < 0.05). The regimens were comparable in mean
change scores on BPCB and FAB at the 4th and 8th week respectively (p > 0.05).
MPDBEEG had higher mean change in PSEB at the 4th and 8th week respectively.
Conclusions: McKenzie Protocol alone, or in combination with static or dynamic
back extensors endurance exercise has comparable effect on FAB, PSEB and BPCB in
patients with LBP. The addition of dynamic endurance exercise to the MP led to
significantly higher positive effects on PSEB.
PMID- 29340180
TI - Interrater and intrarater reliability and minimal detectable change of the
Wisconsin Gait Scale when used to examine videotaped gait in individuals post
stroke.
AB - Background: Often, interventions targeting the kinematic and temporal and spatial
changes in gait commonly seen after a stroke are based on observations of
walking. Having the capacity to objectively identify such changes and track
improvements over time using reliable and valid measures is important. The
Wisconsin Gait Scale (WGS), which is comprised of 14 items, was developed
specifically to examine and document gait changes occurring after a stroke. The
purpose of the study was to explore the interrater and intrarater reliability and
minimal detectable change (MDC) of the WGS when used by physical therapists to
examine gait in adults post-stroke. Methods: Fourteen physical therapists from 3
different acute inpatient rehabilitation centers rated videotapes of the gait of
6 adults post-stroke using the WGS. To minimize subject variability from fatigue,
videotapes created by using 4 cameras provided right and left lateral, anterior,
and posterior views of walking on a level surface. One complete ambulation trial
from each subject post-stroke, which included 4 views of the same ambulation
trial, was examined by the licensed physical therapists using the WGS. An
opportunity was provided to review the tool and a practice trial was performed
using an additional videotape not included in the analysis. Gait was examined on
2 different occasions separated by a period of approximately 21 days to minimize
the effects of recall bias. Intraclass Correlation Coefficients (ICC) were used
to examine the interrater and intrarater reliability of the WGS. Results:
Interrater (ICC = 0.83) and intrarater (ICC = 0.91) reliability were both good.
The standard error of the measurement (SEM) was 1.47 and the MDC95 was 4.24.
There was no statistically significant difference between the scores on the WGS
when comparing the 2 different sessions. Conclusions: The WGS shows promise as an
instrument that can make observational gait analysis more reliable. High
intrarater reliability and low SEM suggests that the WGS is stable when
administered across multiple sessions by the same rater. The ICC for interrater
reliability was also good, which suggests that multiple examiners can effectively
use the instrument. With minimal training, the physical therapists in the study
were able to produce highly reliable results using the WGS to objectively
document gait dysfunction.
PMID- 29340181
TI - Effects of walking on bilateral differences in spatial attention control: a cross
over design.
AB - Background: Walking requires a high attentional cost for balance control and
interferes with the control of attention. However, it is unclear whether the
performance of visual spatial attention control, which is one of the functions of
attention control, is also decreased during walking. In addition, although
previous studies have shown right-hemispheric dominance and lower ability of left
side visual spatial attention control during sitting, it remains unknown whether
walking accentuates bilateral differences in visual spatial attention control. We
tested the hypothesis that walking interferes with visual spatial attention
control on both sides and accentuates its bilateral differences. Methods: Twenty
healthy right-handed subjects (24.3 +/- 2.0 years) participated in this study.
Subjects performed a random stimulus-response compatibility (SRC) task during
both sitting and walking situations. To evaluate the effects of walking, reaction
time was measured on both sides for the two situations. In comparison to the both
situations (sitting and walking), the amount of change of the SRC effect on both
sides was used. In the comparing the bilateral difference (left and right), the
difference of the SRC effect was evaluated in each situation. The paired t-test
was applied to both comparisons for statistical analysis. Results: The SRC effect
on both sides during walking was significantly larger than during sitting (P <
0.05). In addition, walking significantly accentuated the bilateral differences
in visual spatial attention control (P < 0.05). Conclusions: These results
suggest that walking affects the performance of visual spatial attention control
on both sides and accentuates its bilateral differences. These results have
implications for development of practice methods of gait disorder with higher
brain dysfunction.
PMID- 29340182
TI - Differences in personal and lifestyle characteristics among Zimbabwean high
school adolescents with and without recurrent non-specific low back pain: a two
part cross-sectional study.
AB - Background: Recurrent non-specific low back pain (NSLBP) is increasingly becoming
common among adolescents worldwide. A recent study in Zimbabwe showed a
relatively high prevalence (28.8 %) among high school students. Influential
associated factors, however, remain unclear. This is a significant shortcoming.
The aim was to determine personal or lifestyle-related factors associated with
recurrent NSLBP among high school adolescents in Harare, Zimbabwe. Methods: This
study was part of a large epidemiological study conducted in two continuous
parts. Part one sought to determine self-reported associated factors among 532
participants (mean age =16 +/- 1.72 years) drawn randomly from selected
government schools using a reliable and content-validated questionnaire (Kappa
coefficient, k = 0.32-1). Part two purposively identified adolescents (N = 64,
median age =17 years, interquartile range, IQR = 15-18 years) with a history of
'severe' recurrent NSLBP from part one based on a specific eligibility criteria
and compared body mass index, relative school bag weight and hamstring
flexibility with matched adolescents without NSLBP. Data was analysed using
Statistica version 11. Independent t-tests or chi2 tests of association were used
for continuous and categorical data, respectively. The statistical significance
was set at p < .05. Results: Recurrent NSLBP was associated with self-reported
factors such as perceptions of a heavy school bag [chi2 (1) = 85.9, p < 0.001]. A
significant proportion of adolescents with recurrent NSLBP spent over 30 min
carrying the school bag to and from school [chi2 (1) =32.2, p < 0.001]. It was
also associated with prolonged sitting (p < 0.001), not playing sports [chi2 (1)
=5.85, p = 0.02] and tight hamstrings [chi2 (1) =7.6, p = 0.006]. Conclusions:
Although conclusions from this study are hesitant because of the cross-sectional
nature of the study and the relatively small sample size in follow-up study,
recurrent NSLBP is associated with perceptions of a heavy school bag, duration of
school bag carriage, no sports participation, prolonged sitting on entertainment
activities, and tight hamstrings. These findings add to the importance of
promoting physical activity at school or home especially aimed at improving
muscle flexibility.
PMID- 29340183
TI - Action observation training to improve motor function recovery: a systematic
review.
AB - Following the discovery of Mirror Neuron System (MNS), Action Observation
Training (AOT) has become an emerging rehabilitation tool to improve motor
functions both in neurologic and orthopedic pathologies. The aim of this study is
to present the state of the art on the use of AOT in experimental studies to
improve motor function recovery in any disease. The research was performed in
PubMed, PEDro, Embase, CINAHL and Cochrane Central Register of Controlled Trials
(last search July 2015). Randomized controlled trials (RCTs) that analyse
efficacy of AOT for recovery of motor functions, regardless of the kind of
disease, were retrieved. The validity of the included studies was assessed using
the Cochrane Collaboration tool for evaluating risk of bias. Twenty RCTs were
eligible. Four studies showed AOT efficacy in improving upper limb functional
recovery in participants with chronic stroke, two studies in sub-acute ones and
one in acute ones. Six articles suggested its effectiveness on walking
performance in chronic stroke individuals, and three of them also suggested an
efficacy in improving balance. The use of AOT was also recommended in individuals
with Parkinson's disease to improve autonomy in activities of daily living, to
improve spontaneous movement rate of self-paced finger movements and to reduce
freezing of gait. Other two studies also indicated that AOT improves upper limb
motor function in children with cerebral palsy. The last two studies, showed the
efficacy of AOT in improving motor recovery in postsurgical orthopedic
participants. Overall methodological quality of the considered studies was
medium. The majority of analyzed studies suggest the efficacy of AOT, in addition
to conventional physiotherapy, to improve motor function recovery in individuals
with neurological and orthopedic diseases. However, the application of AOT is
very heterogeneous in terms of diseases and outcome measures assessed, which
makes it difficult to reach, to date, any conclusion that might influence
clinical practice.
PMID- 29340184
TI - Aerosol delivery practice in Italian Cystic Fibrosis centres: a national survey.
AB - Background: Physiotherapists (PTs) are ideally positioned to assist patients and
families with inhalation therapies through monitoring, communication and
education about available therapies and their proper use; indeed aerosoltherapy
management is listed as part of Italian PTs' core competence and in the core
syllabus for post-graduate training in respiratory physiotherapy. The aim of this
study was to outline the involvement of Italian PTs working in Cystic Fibrosis
(CF) centres in the aerosol delivery practice. Methods: Physiotherapist
coordinators (n = 29) of all Italian CF centres were invited to participate in a
cross-sectional survey and a semi-structured questionnaire was developed and sent
by e-mail. Results: A response rate of 69 % was achieved. The majority of
participants were woman and the overall mean professional experience was twenty
years. Italian PTs are involved in the aerosol delivery practice, managing
education, drug-device combination, dilution and mixing of drugs. Conclusions:
Physiotherapists play a key role in the care of Italian CF patients; nevertheless
the Italian Group of Physiotherapists might plan interventions to harmonize the
aerosol delivery practice in Italian CF centres and to sustain continuing
education.
PMID- 29340185
TI - Physical fitness of Ghanaian physiotherapists and its correlation with age and
exercise engagement: a pilot study.
AB - Background: The physical job demands of physiotherapists require optimal level of
physical fitness (PF), which is often not evaluated in practice. In this study,
we assessed selected components of physical fitness of Ghanaian physiotherapists
in relation to their sex, age and frequency of exercise participation. Methods:
Physiotherapists practicing in four major hospitals within the Accra Metropolis
of Ghana were enrolled into this cross-sectional survey. Three major components
of physical fitness (flexibility, cardiorespiratory endurance and body
composition) were assessed with sit and reach test, 3-min step test and BMI
respectively. Unpaired sample t-test was used to determine differences in means
of the three components of physical fitness betwwen males and females. Pearson
correlation coefficient showed that frequency of exercise engagement and age of
the participants correlated with the three components of physical fitness at p <
0.05. Results: The study sample consisted of 40 participants, out of which 23 (58
%) were females. The mean age was (31.5 +/- 1.4) years and majority 21 (52.5 %)
was within the age range of 20-29 years. Respective mean scores for
cardiorespiratory endurance, flexibility and BMI were (98.2 +/- 12.9 beat/min),
(4.03 +/- 6.15 cm) and (23.3 +/- 3.4 kg/m2). Female participants were
significantly more flexible than their male counterparts (5.7 +/- 5.3; 1.6 +/-
6.6, p = 0.034). There was a positive and significant correlation between the age
of the participants and BMI (r = 0.614 and p = 0.017). However, cardiorespiratory
endurance was not significantly correlated with age and frequency of exercise
engagement. Conclusions: The sampled physiotherapists had relatively low physical
fitness compared to the age adjusted values. Age and sex are therefore crucial
determinants whilst designing programmes aimed at promoting physical fitness in
this group.
PMID- 29340187
TI - Motor rehabilitation should be based on knowledge of motor control.
AB - Neurorehabilitation is at a crossroads. Indeed, there is inconclusive, but
promising evidence about clinical effectiveness of rehabilitation in the field of
neurological impairments. Translating the new theories on motor control into
clinical research may help to develop new treatment strategies and guide
rehabilitation approaches. The concepts of synergy and the uncontrolled manifold
hypothesis provide a strong theoretical framework to explain how the nervous
system controls and coordinates movements, ensuring stability during daily
actions. Moreover, this approach can increase the understanding of the neural
control of action stability with implications for clinical practice and may help
the development of new treatment strategies.
PMID- 29340188
TI - At discharge gait speed and independence of patients provides a challenges for
rehabilitation after total joint arthroplasty: an observational study.
AB - Background: The level of functioning in people discharged from hospital after hip
arthroplasty is very heterogeneous and prognostic factors are not fully
understood. The aim of this study was to determine the mean level of autonomy
achieved by such patients at discharge from hospital using the Iowa Level of
Assistence (ILOA) scale as a measurement tool and to investigate the possible
predictive factors of this autonomy. Methods: It was conducted a prospective
cohort study including hip arthroplasty patients treated consecutively in 2012.
Hip arthroplasty patients following fractures, revision surgery and partial
replacement were excluded, as well as patients with concomitant neurologic or
rheumatologic diseases or postoperative complications that did not allow to
continue the rehabilitation program, and patients with a hospitalization of more
than 7 days. During the last 24 h of hospital stay the physiotherapist filled in
the ILOA scale and collected all data (age, gender, number of physiotherapy
treatments, length of hospitalization). Statistical analysis (univariate and
multivariate analysis) was performed between the variables collected and the ILOA
Score. Results: The sample was composed of 167 patients. The mean score of the
ILOA was 16.6 (+/-6.5) and gait speed had the poorest outcome 0.19 m/s - 0.43
m/s. Multivariate analysis showed that older women are most at risk of not
achieving good levels of autonomy. Conclusions: In hip arthroplasty patients at
discharge from hospital gait speed is severely impaired. The challenge for
rehabilitation should be to recover walking ability and efficiency starting from
the early post-operative period. Gender- and age-tailored rehabilitation programs
should be considered by placing particular attention on elderly women.
PMID- 29340189
TI - A cross-sectional study investigating impressions and opinions of medical
rehabilitation professionals on the effectiveness of the Ponseti method for
treatment of clubfoot in Harare, Zimbabwe.
AB - Background: The Ponseti method of managing clubfoot was introduced in Zimbabwe in
2011. This followed massive training of health workers such as medical
rehabilitation practitioners through a programme called the Zimbabwe Sustainable
Clubfoot Programme. Today, the Ponseti method is the technique of choice for
managing clubfoot in hospitals. However, since then, there is no published
evidence documenting the efficacy and the relevance of the technique especially
comparing to previously used methods. This is a significant shortcoming if
sustainability issues are to be considered. Therefore, this study was designed to
investigate the impressions and opinions of medical rehabilitation practitioners
on the method in terms of its effectiveness, perceived challenges and possible
recommendations for improvement of the technique application in their setting.
Methods: A descriptive cross-sectional study was conducted targeting medical
rehabilitation practitioners previously trained on the method and working in
public or private clinics that offer clubfoot management in Harare. A
questionnaire was self-administered to 41 participants who volunteered to
participate in the study. Data from open-ended questions was analysed
thematically. Statistica version 12 was used for analysis for quantitative data.
Results: The Ponseti method was perceived as an effective method in the treatment
of children with clubfoot by all the participants. All the participants 41 (100
%) felt that the method was relevant because of better clinical outcomes. Amongst
challenges faced when using Ponseti method, 25 (61 %) participants agreed that
caregivers to the children with clubfoot were not compliant to treatment. A total
of 22 (54 %) participants felt that lack of adequate insight by the caregivers of
this new method was a challenge which hinder progress in treating clubfoot.
Conclusions: The medical rehabilitation professionals in Harare, Zimbabwe trained
to use the Ponseti technique for the management of clubfoot, perceived the method
as an effective method resulting in better clinical outcome than previous
methods. This probably highlights the need to continue training medical
rehabilitation professionals so that there is widespread use of the technique in
the country. However, there is need to increase awareness of the method among
caregivers to improve compliance, which is key to successful rehabilitation of
the clubfoot.
PMID- 29340190
TI - Consequences and management of neck pain by female office workers: results of a
survey and clinical assessment.
AB - Background: Neck pain is common in office workers. However, the functional
consequences of this pain to the individual and how they are managed are not well
known. The objective of this study is understand the impact of neck pain and the
strategies female office workers use to manage their pain while remaining at
work. Methods: Female office workers with neck pain (n = 174) completed a survey
about the impact of their neck pain, with 51 attending a university clinic for
further assessment. Consequences of neck pain were evaluated with questions on
self-reported work absence, workers' compensation claims, health care use, impact
on work and leisure activity, and management strategies. Responses to survey
questions were analysed using descriptive analyses. Results: The results showed
that during the preceding 12 months, 57.5 % of participants had consulted a
health professional due to neck pain; 42 % had reduced their leisure activities;
22.4 % had reduced their work activity and 20.7 % had been absent from work. Only
5.2 % had ever submitted a workers' compensation claim and 9 % indicated changing
jobs due to neck pain. Of the 51 participants who attended for further
assessment, 35.3 % indicated they 'self-managed' their neck pain with
conventional medical strategies. Common strategies utilized were: prescription or
over-the-counter medications (82.5 %), physiotherapy (64.7 %) and visiting their
general medical practitioner (54.9 %). Conclusions: Although the severity of neck
pain experienced by female office workers in this study was low, the impact on
work and leisure was substantial. These workers tended to self-manage their pain
by reducing work and/or leisure activity and utilizing passive coping strategies
to remain at work. Physiotherapists are ideally suited to provide self-management
strategies to ensure workers remain healthy while working.
PMID- 29340192
TI - Use of social media among Italian physiotherapists: a new opportunity for the
profession or an unfavorable trend toward guruism?
AB - The advent of social media such as Facebook has introduced new opportunities for
knowledge sharing and professional networking. Currently, little is known on how
physiotherapists participate in virtual communities, and there are opposing views
regarding the benefits and pitfalls of professional use of social media. In this
letter, theoretical frameworks are proposed by analyzing the behavior of users
and the post contents on Italian pages dedicated to physiotherapy. There is also
an urgent need to evaluate whether virtual communities may improve final patient
outcomes.
PMID- 29340191
TI - Patient-reported outcome measures for non-specific neck pain validated in the
Italian-language: a systematic review.
AB - Background: Patient-reported outcome measures can improve the management of
patients with non-specific neck pain. The choice of measure greatly depends on
its content and psychometric properties. Most questionnaires were developed for
English-speaking people, and need to undergo cross-cultural validation for use in
different language contexts. To help Italian clinicians select the most
appropriate tool, we systematically reviewed the validated Italian-language
outcome measures for non-specific neck pain, and analyzed their psychometric
properties and clinical utility. Methods: The search was performed in MEDLINE,
EMBASE, CINAHL, Scopus, Web of Science, and Cochrane Library. All articles
published in English or Italian regarding the development, translation, or
validation of patient-reported outcome measures available in the Italian language
were included. Two reviewers independently selected the studies, extracted data,
and assessed methodological quality using the COSMIN checklist. Results: Out of
4891articles screened, 66 were eligible. Overall, they were of poor or fair
methodological quality. Four instruments measuring function and disability (Neck
Disability Index, Neck Pain and Disability Scale, Neck Bournemouth Questionnaire,
and Core Outcome Measures Index), and one measuring activity-related fear of
movement (NeckPix(c)) were identified. Each scale showed some psychometric
weaknesses or problems with functioning, and none emerged as a gold standard.
Conclusions: Several patient-reported outcome measures are now available for
assessing Italian people with non-specific neck pain. While the Neck Disability
Index is the one most widely used, the Neck Bournemouth Questionnaire appears the
most promising tool from a psychometric point of view.
PMID- 29340193
TI - Implementation of the physical function ICU test tool in a resource constrained
intensive care unit to promote early mobilisation of critically ill patients- a
feasibility study.
AB - Background: The shift of focus in outcome measures from mortality to assessment
of functional status in intensive care unit (ICU) patients has resulted in the
emergence of mobilisation of critically ill patients as a standard physiotherapy
practice in most medium and high income countries. The aim of this study was to
determine the feasibility of an early mobilisation program and to report on the
changes in patient clinical outcomes following the intervention in a low income
country. Methods: A prospective cohort study was carried out at one public
hospital. An adult cohort of 35 patients was recruited within 24 h of being
admitted into the unit, irrespective of ventilation method over a period of three
months. An early mobilisation programme was implemented and prescribed using the
Physical Function ICU Test (PFIT-s) which commenced in either the ICU or high
dependent unit. Results: The median age of the 35 patients was 29 years (IQR = 24
45 years). More than half of the patients had undergone surgery due to either
gastrointestinal problems or obstetrical complications. A total of 94 out of a
possible of 219 exercise sessions were delivered to the patients (43.0 %). The
tool was implemented in 32 (91.4 %) patients on the initial PFIT-s measurement
and 16 (45.7 %) of the patients required the assistance of two people to stand.
The Initial PFIT-s mean score was 5.3 +/- 1.8. On final PFIT-s measurement, out
of the 30 (85.7 %) patients seen, 15 (42.9 %) of the patients did not require any
assistance to stand and the final PFIT-s mean score was 7.0 +/- 1.9. There was a
significant difference in both the initial PFIT-s total score (t-value = 2.34, df
= 30, p = .03) and the final PFIT-s score (t-value = 3.66, df = 28, p = .001)
between males and females. During the treatment, no adverse event occurred in any
of the patients. Conclusion: An early mobilisation program using PFIT-s was
feasible and safe. There was a difference in functional capability based on
gender, with males being more functionally active. Specific inclusion and
exclusion criteria can lead to a delayed early mobilisation activities in ICU
patients. Trial registration: Pan African Clinical Trials Registry
PACTR201408000829202. Registered 15 August 2014.
PMID- 29340194
TI - Measurement properties of the upright motor control test for adults with stroke:
a systematic review.
AB - Background: The Upright Motor Control Test (UMCT) has been used in clinical
practice and research to assess functional strength of the hemiparetic lower limb
in adults with stroke. It is unclear if evidence is sufficient to warrant its
use. The purpose of this systematic review was to synthesize available evidence
on the measurement properties of the UMCT for stroke rehabilitation. Methods:
Electronic databases that indexed biomedical literature were systematically
searched from inception until October 2015 (week 4): Embase, PubMed, Web of
Science, CINAHL, PEDro, Cochrane Library, Scopus, ScienceDirect, SPORTDiscus,
LILACS, DOAJ, and Google Scholar. All studies that had used the UMCT in the time
period covered underwent hand searching for any additional study. Observational
studies involving adults with stroke that explored any measurement property of
the UMCT were included. The COnsensus-based Standards for the selection of health
Measurement INstruments was used to assess the methodological quality of included
studies. The CanChild Outcome Measures Rating Form was used for extracting data
on measurement properties and clinical utility. Results: The search yielded three
methodologic studies that addressed criterion-related validity and contruct
validity. Two studies of fair methodological quality demonstrated moderate-level
evidence that Knee Extension and Knee Flexion subtest scores were predictive of
community-level and household-level ambulation. One study of fair methodological
quality provided limited-level evidence for the correlation of Knee Extension
subtest scores with a laboratory measure of ground reaction forces. No published
studies formally assessed reliability, responsiveness, or clinical utility.
Limited information on responsiveness and clinical utility dimensions could be
inferred from the included studies. Conclusions: The UMCT is a practical
assessment tool for voluntary control or functional strength of the hemiparetic
lower limb in standing in adults with stroke. Although different levels of
evidence suggest that the Knee Extension and Knee Flexion subtests may possess
criterion and construct validity, the lack of published literature examining
content validity, reliability, and responsiveness raises questions regarding the
use of the UMCT in routine clinical practice. These key findings highlight the
need to further investigate the UMCT's measurement properties toward enhancing
its standardization.
PMID- 29340195
TI - Combined treatment with paraffin, manual therapy, pegboard and splinting in a
patient with post-traumatic stiff hand.
AB - Background: The stiff hand is a still common, severe complication of hand
injuries. Case presentation: We report here the case of a 56 year-old woman,
professional goldsmith, who suffered a distal radius fracture of her right hand.
The patient was treated with surgery followed by four weeks of immobilization,
and developed a stiff hand. Physical examination showed mild inflammatory signs,
pain and a major limitation in the extension and supination of the wrist, and in
the mobility of the II, III, IV and V metacarpophalangeal (-5 degrees and 32
degrees of average passive extension and flexion, respectively) and
interphalangeal (-35 degrees and 73 degrees of average passive extension and
flexion, respectively) joints. There was a lack of slip of the flexor tendons.
The diagnosis of complex regional pain syndrome was considered although it could
not be definitely established. After five months of adverse evolution the patient
was referred to our center where a combined intervention with paraffin, manual
therapy, prolonged active and passive stretch on a pegboard, and splinting was
applied. After initiation of this therapy, a marked change in the evolution of
the pain, the mobility and functionality of the hand was observed. At the end of
the rehabilitation program the patient was able to fully resume her job.
Conclusion: The present case illustrates the need of intensive treatment for post
traumatic hand stiffness, and describes, as an original contribution, a combined
intervention therapy including paraffin, manual therapy, pegboard and splinting.
PMID- 29340196
TI - A therapist-focused knowledge translation intervention for improving patient
adherence in musculoskeletal physiotherapy practice.
AB - Background: Nonadherence to treatment remains high among patients with
musculoskeletal conditions with negative impact on the treatment outcomes, use of
personal and cost of care. An active knowledge translation (KT) strategy may be
an effective strategy to support practice change. The purpose of this study was
to deliver a brief, interactive, multifaceted and targeted KT program to improve
physiotherapist knowledge and confidence in performing adherence enhancing
activities related to risk, barriers, assessment and interventions. Methods: We
utilised a 2-phase approach in this KT project. Phase 1 involved the development
of an adherence tool kit following a synthesis of the literature and an iterative
process involving 47 end-users. Clinicians treating patients with musculoskeletal
conditions were recruited from two Physiotherapy and Occupational therapy
national conferences in Canada. The intervention, based on the acronym SIMPLE
TIPS was tested on 51 physiotherapists in phase 2. A pre- and post-repeated
measures design was used in Phase 2. Graham's knowledge-to-action cycle was used
as the conceptual framework. Participants completed a pre-intervention
assessment, took part in a 1-h educational session and completed a post
intervention assessment. A questionnaire was used to measure knowledge of
evidence-based treatment adherence barriers, interventions and measures and
confidence to perform evidence-based adherence practice activities. Data was
analysed using descriptive statistics (frequency and percentage), Fisher's exact
test and Wilcoxon Sign-Ranked tests. Results: Barriers and facilitators of
adherence were identified under three domains (therapist, patient, health system)
in phase 1. Seventy percent of the participants completed the questionnaire.
Results indicated that 46.8% of respondents explored barriers including the use
of behaviour change strategies and 45.7% reported that they measured adherence
but none reported the use of validated outcomes. A significant improvement in
post-self-efficacy scores for the four adherence enhancing activities was
observed immediately after the workshop. Conclusion: The use of a multi-modal KT
intervention is feasible in an educational setting. A brief interactive
educational session was successfully implemented using a toolkit and caused a
significant increase in physiotherapists' knowledge and confidence at performing
adherence enhancing activities in the very short-term. Further testing of SIMPLE
TIPS on long-term adherence practices could help advance best practices specific
to treatment adherence in MSK practice.
PMID- 29340197
TI - Hemodynamics and tissue oxygenation effects after increased in positive end
expiratory pressure in coronary artery bypass surgery.
AB - Background: Cardiac surgery is widely used in the treatment of cardiovascular
diseases. However, several complications can be observed during the postoperative
period. Positive end expiratory pressure (PEEP) improves gas exchange, but it
might be related to decreased cardiac output and possible impairment of tissue
oxygenation. The aim of this study was to investigate the hemodynamic effects and
oxygen saturation of central venous blood (ScvO2) after increasing PEEP in
hypoxemic patients after coronary artery bypass (CAB) surgery. Methods: Seventy
post-cardiac surgery patients (CAB), 61 +/- 7 years, without ventricular
dysfunction (left ventricular ejection fraction 57 +/- 2%), with hypoxemia
(PaO2/FiO2 ratio <200) were enrolled. Heart rate, mean arterial pressure,
arterial and venous blood samples were measured at intensive care unit and PEEP
was increased to 12 cmH2O for 30 min. Results: As expected, PEEP12 improved
arterial oxygenation and PaO2/FiO2 ratio (p < 0.0001). Reduction in ScvO2 was
observed between PEEP5 (63 +/- 2%) and PEEP12 (57 +/- 1%; p = 0.01) with higher
values of blood lactate in PEEP12 (p < 0.01). No hemodynamic effects (heart rate,
mean arterial pressure, SpO2; p > 0.05) were related. Conclusion: Increased PEEP
after cardiac surgery decreased ScvO2 and increased blood lactate, even with
higher O2 delivery. PEEP did not interfere in hemodynamics status in CAB
patients, suggesting that peripheral parameters must be controlled and measured
during procedures involving increased PEEP in post-cardiac surgery patients in
the intensive care unit.
PMID- 29340198
TI - Content validity and test-retest reliability of a low back pain questionnaire in
Zimbabwean adolescents.
AB - Background: In Zimbabwe, a recent increase in the volume of research on recurrent
non-specific low back pain (NSLBP) has revealed that adolescents are commonly
affected. This is alarming to health professionals and parents and calls for
serious primary preventative strategies to be developed and implemented
forthwith. Early identification initiatives should be prioritised in order to
curtail the condition and its progression. In an attempt to be proactive in
minimising the prevalence of recurrent NSLBP, this study was conducted to
evaluate the content validity and test-retest reliability of a survey
questionnaire with the aim of proffering a valid and reliable questionnaire which
can be used in non-clinical settings to identify adolescents with recurrent NSLBP
in Harare, Zimbabwe and determine the possible factors associated with the
condition. Methods: The study was conducted in two parts. The first part assessed
content validity of the questionnaire using four experts derived from academia
and clinical practice. The second part evaluated the reliability of the
questionnaire among 125 high school-children aged between 13 and 19 years in a
test-retest study. Results: Twenty-six (26) out of thirty questions in the
questionnaire had an Item Content Validity index of 1.00, demonstrating complete
agreement among content experts. Overall, the Scale Content Validity Index for
the questionnaire was 0.97. Item completion for the reliability study was
satisfactory. The questionnaire items had kappa values ranging from 0.17 (slight
agreement) to 1 (perfect agreement). High levels of reliability were found for
the questions on school bag use (k=0.94), sports participation (k=0.97), and
lifetime prevalence (k=0.89). Conclusion: Excellent content validity and slight
to perfect test-retest reliability was found for the Low Back Pain (LBP)
questionnaire. These results are comparable to findings of other studies
evaluating the psychometric properties of LBP questionnaires. Cognisant of the
limitations of the study, the results of this study suggest that the LBP
questionnaire could be used in local studies investigating LBP among adolescents
although questions enquiring on functional limitations and sciatica may need
further consideration.
PMID- 29340199
TI - Depicting individual responses to physical therapist led chronic pain self
management support with pain science education and exercise in primary health
care: multiple case studies.
AB - Background: Previous evidence suggests self-management programs for people with
chronic pain improve knowledge and self-efficacy, but result in small to
negligible changes in function. The purpose of this multiple case studies design
was to describe the unique responses of six participants to a new self-management
program aimed at improving function, to detail each component of the program, and
to explore potential explanations for the varied trajectories of each of the
participants. Case Presentation: Six participants who had been experiencing
chronic pain for at least 5 years were included. All participants were enrolled 6
weeks of ChrOnic pain self-ManageMent support with pain science EducatioN and
exercise (COMMENCE). Participants completed an assessment at baseline, 7 weeks (1
week follow-up), and 18 weeks (12-week follow-up). Each participant had a unique
initial presentation and goals. Assessments included: function as measured by the
Short Musculoskeletal Function Assessment - Dysfunction Index, how much
participants are bothered by functional difficulties, pain intensity, fatigue,
pain interference, cognitive and psychological factors associated with pain and
disability, pain neurophysiology, self-efficacy, satisfaction, and perceived
change. The self-management program was 6-weeks in length, consisting of one
individual visit and one group visit per week. The program incorporated three
novel elements not commonly included in self-management programs: pain
neurophysiology education, individualized exercises determined by the
participants' goals, and additional cognitive behavioural approaches.
Participants were all satisfied with self-management support received. Change in
function was variable ranging from 59% improvement to 17% decline. Two potential
explanations for variances in response, attendance and social context, are
discussed. Several challenges were identified by participants as barriers to
attendance. Conclusions: A primary care self-management intervention including
pain education and individualized exercise has potential to improve function for
some people with chronic pain, although strategies to improve adherence and
reduce barriers to participation may be needed to optimize the impact.
PMID- 29340200
TI - A survey of physicians and physiotherapists on physical activity promotion in
Nigeria.
AB - Background: Effective control of non-communicable diseases and promotion of
population-wide physical activity participation require the active engagement of
health professionals. Physiotherapists and physicians, as part of their practice,
routinely screen and assess physical activity status, and recommend health
enhancing physical activity participation for their patients. This study aims to
compare Nigerian physiotherapists and physicians' knowledge of physical activity
message, role perception and confidence, perceived feasibility and barriers, and
overall disposition to promoting physical activity in their practice. Methods: A
total of 153 physicians and 94 physiotherapists recruited from 10 government
hospitals in five states in Northern Nigeria completed a standardized physical
activity promotion questionnaire that elicited information on the knowledge of
physical activity, role perception and confidence, feasibility, and barriers to
physical activity promotion. Descriptive and inferential statistics were used to
analyze the data. Results: The physiotherapists and physicians were fairly
knowledgeable on physical activity message (14.2 +/- 2.1/20), reported minimal or
little barrier to physical activity promotion (23.7 +/- 3.1/30), perceived
physical activity promotion as their role (13.0 +/- 1.8/15), were confident in
their ability to discuss and recommend physical activity promotion (7.6 +/-
1.6/10) and believed promoting physical activity was feasible for them (15.6 +/-
2.6/20). However, over 40% of the physiotherapists and physicians do not know the
correct dosage of physical activity that could confer health benefits to
patients. The physicians showed better overall disposition to physical activity
promotion than the physiotherapists (P = 0.048), but more physiotherapists than
the physicians believed 'it is part of their role to suggest to patients to
increase their daily physical activity' (95.7% vs 88.2%, P = 0.043) and were more
'confident in suggesting specific physical activity programs for their patients'
(87.2% vs 64.5%, P < 0.001). Conclusion: Physiotherapists and physicians in
Nigeria demonstrated good disposition to promoting physical activity but many of
them have knowledge deficits on the correct dosage required for better health for
their patients. These health professionals can serve as good advocates for
physical activity promotion in Nigeria, but many of them may require knowledge
update on health enhancing physical activity for effective health promotion and
primary prevention of non-communicable diseases.
PMID- 29340201
TI - Developing the content of a locomotor disability scale for adults in Bangladesh:
a qualitative study.
AB - Background: Bangladesh has an estimated 17 million adults with disabilities. A
significant proportion of them are believed to have locomotor disabilities. There
are over 300 non-governmental organizations providing different types of
rehabilitation services to them. However, there is no locally developed and
validated locomotor disability measurement scale in Bangladesh. The purpose of
this study was to develop a locomotor disability scale with disability indicators
suitable for adults in Bangladesh. Methods: Semi-structured interviews were
conducted with 25 purposively selected adults with locomotor disabilities to
generate scale items. At the second stage, cognitive interviews were conducted
with 12 purposively selected adults with locomotor disabilities in order to
refine the measurement questions and response categories. Data were analysed
using the framework technique- identifying, abstracting, charting and matching
themes across the interviews. Results: For a locomotor disability scale, 70
activities (disability indicators) were identified: 37 mobility activities, 9
activities of daily living, 17 work/productivity activities and 7 leisure
activities. Cognitive interviews revealed that when asking the respondents to
rate their difficulty in performing the activities, instead of just mentioning
the activity name, such as taking a bath or shower, a detailed description of the
activity and response options were necessary to ensure consistent interpretation
of the disability indicators and response options across all respondents.
Conclusions: Identifying suitable disability indicators was the first step in
developing a locomotor disability scale for adults in Bangladesh. Interviewing
adults with locomotor disabilities in Bangladesh ensured that the locomotor
disability scale is of relevance to them and consequently it has excellent
content validity. Further research is needed to evaluate the psychometric
properties of this scale.
PMID- 29340202
TI - Exploring barriers to accessing physiotherapy services for stroke patients at
Tema general hospital, Ghana.
AB - Background: Physiotherapy has been shown to reduce the risk of disability among
stroke patients. Poor adherence to physiotherapy can negatively affect outcomes
and healthcare cost. However, very little is known about barriers especially to
physiotherapy services in Ghana. The objective of this study was to assess the
barriers to physiotherapy services for stroke patients at Tema General Hospital
(TGH). The individual/personal and health system barriers to physiotherapy
services at TGH were determined. Method: A cross-sectional study design was
employed. A simple random sampling technique was used to recruit 207 respondents
for a face-to-face interview. Interviewer-administered questionnaires were used
to collect data on individual/personal barriers of respondents to physiotherapy
services and were described using the Likert's scale. Health system barriers were
assessed using a self-structured questionnaire which had section under the
following heading: human factors, physiotherapy modalities, physical barriers and
material/equipment factors. The time spent waiting for physiotherapy and attitude
of physiotherapist towards patients; physiotherapy modality such as
electrotherapy, exercise therapy and massage therapy among others were some of
the indices measured. Respondents' adherence to Medication was assessed with the
Morisky 8-item medication adherence questionnaire. Data were entered and analysed
using Epi info 7 and STATA 12.0. Associations between the variables were
determined using a chi-square test and logistic regression model was used to test
the strength of associations between the independent and the dependent variables.
The level of statistical significance was set at p < 0.05. Results: The results
showed that majority (76.3%) of the respondents had economic barrier as their
main individual/personal barrier to physiotherapy services. For medication
adherence level, patients with low medication adherence level were about 21 times
the odds of defaulting on accessing physiotherapy services five times or more as
compared to those with medium adherence level (OR 20.63, 95% CI 8.96, 42.97). It
was concluded in the study that individual/personal barriers of stroke patients
were the significant barriers to accessing physiotherapy services at Tema General
Hospital.
PMID- 29340203
TI - Effectiveness of three modes of kinetic-chain exercises on quadriceps muscle
strength and thigh girth among individuals with knee osteoarthritis.
AB - Background: The study was designed to evaluate and compare the effectiveness of
12-week open, closed and combined kinetic-chain exercises (OKCE, CKCE and CCE) on
quadriceps muscle strength and thigh girth of patients with knee osteoarthritis
(OA). Method: The randomized clinical trial involved ninety-six consecutive
patients with knee OA who were randomly assigned to one of OKCE, CKCE or CCE
groups. Participants' static quadriceps muscle strength (SQS), dynamic quadriceps
muscle strength (DQS) and thigh girth (TG) were assessed using cable tensiometer,
one repetition method and inelastic tape measure respectively at baseline and at
the end of weeks 4, 8 and 12 of study. Results: The three groups were comparable
regarding their demographic and dependent variables at baseline; there was
significant time effect (p < 0.001each) as all three measures significantly
increased over time from baseline to week 12 [mean difference: SQS: 3.30 (95% CI:
2.52-4.08) N; DQS: 0.74 (95% CI: 0.45-1.02) N; TG: 1.32 (95% CI: 0.93-1.71) cm].
The effect of intervention-time interaction was not significant (p > 0.05) for
all three measures. Changes in SQS, DQS and TG between baseline and week 12 were
also not significantly different (p > 0.05) among the three groups. Conclusion:
All three exercise regimens are effective and demonstrate similar effects on
quadriceps muscle strength and muscular trophism. Trial registration:
NHREC/05/01/2008a. Registered 20th March, 2014 Retrospectively.
PMID- 29340204
TI - Side alternating vibration training in patients with mitochondrial disease: a
pilot study.
AB - Background: Side alternating vibration training (SAVT) is a mechanical
oscillation using a vibrating platform that simulates exercise. We hypothesized
that patients with mitochondrial myopathies, who experience muscle weakness, may
see an improvement in muscle power with SAVT. Methods: Patients with
mitochondrial disease started either a treatment (SAVT) or control phase
(standing without vibration) for 12 weeks, then 12 weeks of washout, and then a
12-week cross-over. The main outcome measure was peak jump power (PJP). We
compared this to a natural history cohort from clinic. Results: Seven out of 13
patients completed at least 80% of their SAVT sessions and were analyzed. The
DeltaPJP after the control phase was -2.7 +/- 1.7 W/kg (mean +/- SEM), SAVT was
+2.8 +/- 0.6 W/kg (p < 0.05) and from the natural history cohort was -2.4 +/- 0.8
W/kg/year. Conclusions: SAVT is well tolerated and may improve muscle power in
mitochondrial disease patients.
PMID- 29340205
TI - Physiotherapy in upper abdominal surgery - what is current practice in Australia?
AB - Background: Upper abdominal surgery (UAS) has the potential to cause post
operative pulmonary complications (PPCs). In the absence of high-quality research
regarding post-operative physiotherapy management, consensus-based best practice
guidelines formulated by Hanekom et al. (2012) are available to clinicians
providing recommendations for post-UAS treatment. Such best practice guidelines
have recommended that physiotherapists should be using early mobilisation and
respiratory intervention to minimise risk of PPCs. However, recent evidence
supports the implementation of mobilisation as a standalone treatment in PPC
prevention, though the diversity in literature poses questions regarding ideal
current practice. This project aimed to document and report the assessment
measures and interventions physiotherapists are utilising following UAS,
establishing whether current management is reflective of best practice guidelines
and recent evidence. Results: An online survey was completed by 57 experienced
Australian physiotherapists working with patients following UAS (35% survey
response rate, 63% completion rate). On day one following UAS, when a patient's
condition is not medically limited, most physiotherapists routinely mobilise.
Additionally, routine chest treatment continues to be implemented, with only 23%
(n = 11/47) of physiotherapists mobilising patients without accompanying specific
respiratory intervention. Variability of screening tools used to identify post
operative patients at high risk of PPC development was evident. Patient-dependent
factors such as 'fatigue' and 'non-compliance' were among those identified as
barriers to treatment, all influencing the commencement of treatment.
Conclusions: Physiotherapists indicated that early mobilisation away from the
bedside was the preferred post-operative treatment within the UAS patient
population. Many continue to perform routine respiratory interventions despite
recent literature suggesting it may provide no additional benefit to preventing
PPCs. Current intervention choice is reflective of guidelines [1], however,
recent literature has called this into question and more research needs to be
done to establish if these recommendations are the most effective at reducing
PPCs. Continued research is necessary to promote translation of knowledge to
ensure physiotherapists are mobilising patients day one post-UAS. Likewise,
future work should focus on identification of barriers, the strategies used to
overcome limitations and the creation of a reliable and validated screening tool
to ensure appropriate prioritisation and allocation of physiotherapy resources
within the UAS patient population.
PMID- 29340206
TI - How to diagnose cervicogenic dizziness.
AB - Cervicogenic dizziness (CGD) is a clinical syndrome characterized by the presence
of dizziness and associated neck pain. There are no definitive clinical or
laboratory tests for CGD and therefore CGD is a diagnosis of exclusion. It can be
difficult for healthcare professionals to differentiate CGD from other
vestibular, medical and vascular disorders that cause dizziness, requiring a high
level of skill and a thorough understanding of the proper tests and measures to
accurately rule in or rule out competing diagnoses. Consequently, the purpose of
this paper is to provide a systematic diagnostic approach to enable healthcare
providers to accurately diagnose CGD. This narrative will outline a stepwise
process for evaluating patients who may have CGD and provide steps to exclude
diagnoses that can present with symptoms similar to those seen in CGD, including
central and peripheral vestibular disorders, vestibular migraine, labyrinthine
concussion, cervical arterial dysfunction, and whiplash associated disorder.
PMID- 29340207
TI - Participation in physical activities for children with cerebral palsy:
feasibility and effectiveness of physical activity on prescription.
AB - Background: Children with cerebral palsy (CP) are less physically active and more
sedentary than other children which implies risk factors for their physical and
mental health. Physical activity on prescription (PAP) is an effective
intervention to promote a lifestyle change towards increased physical activity in
adults in general. Knowledge is lacking about the use of PAP in children with CP.
Therefore, the aim of this study was to evaluate the feasibility of PAP for
children with CP and its effectiveness on participation in physical activity and
sedentary behaviour. Methods: Eleven children with CP, aged 7-11 years,
participated in PAP, consisting of a written agreement between each child, their
parents and the physiotherapist and based on Motivational Interviewing (MI),
Canadian Occupational Performance Measure (COPM) and Goal Attainment Scaling
(GAS). Individual goals, gross motor function and physical activity were assessed
at baseline, at 8 and/or 11 months using COPM, GAS, logbooks, Gross Motor
Function Measure (GMFM-66), physical activity questionnaires, physical activity
and heart rate monitors and time-use diaries. At 8 and 11 months the feasibility
of the intervention and costs and time spent for the families and the
physiotherapist were evaluated by questionnaires. Results: The intervention was
feasible according to the feasibility questionnaire. Each child participated in 1
3 self-selected physical activities during 3-6 months with support from the
physiotherapist, and clinically meaningful increases from baseline of COPM and
GAS scores were recorded. Being physically active at moderate-vigorous levels
varied between less than 30 and more than 240 minutes/day, and the median for the
whole group was 84 minutes/day at baseline and 106 minutes/day at 8 months.
Conclusions: The intervention PAP seems to be feasible and effective for children
with CP, involving both every day and organised physical activities to promote an
active lifestyle through increased participation, motivation, and engagement in
physical activities. Further research of PAP is needed, preferably in a long term
randomised controlled trial and including health economic analysis to show costs
and benefits. Trial Registration: ISRCTN76366356, retrospectively registered.
PMID- 29340208
TI - Are they publishing? A descriptive cross-sectional profile and bibliometric
analysis of the journal publication productivity of Italian physiotherapists.
AB - Background: In a clinical science-based profession such as physiotherapy,
research is mandatory to update knowledge and to provide cost-effective, high
quality treatments. This study aimed to provide point prevalence of Italian
physiotherapists who are academics, holding a PhD degree, or being authors of
scientific papers. The scientific journal productivity of physiotherapists was
also thoroughly analyzed. Methods: A descriptive cross-sectional study was
carried out on all Italian physiotherapists. Academics, postdoctoral research
fellows, and PhD graduates were identified by searching the Italian Ministry of
Education, University and Research (MIUR), Italian Society of Physiotherapy, and
university websites. Then, authors of articles indexed in Scopus were searched.
The following data were extracted: type of affiliation, authorship order, H
index, number of publications and citations, name of journals, year of
publication, and journal's Impact Factor. Results: The prevalence of academics,
physiotherapists holding a PhD, or being author was 0.01%, 0.05%, and 0.56%,
respectively. We identified 1083 papers co-authored by Italian physiotherapists,
and their number has progressively increased over the years (p < 0.001). There
was a significant difference between researchers and clinicians in both
publication productivity (p < 0.01), citations (p < 0.01), and H-Index (p =
0.05). Articles were published in 359 different journals, receiving a total of
13,373 citations. Conclusions: Despite the low prevalence of faculty members and
the reduced availability of PhD programs in Italy (forcing some students to study
abroad), the quantity and quality of journal productivity is growing fast, and an
increasing number of physiotherapists are involved in research activities.
PMID- 29340210
TI - TreeTime: Maximum-likelihood phylodynamic analysis.
AB - Mutations that accumulate in the genome of cells or viruses can be used to infer
their evolutionary history. In the case of rapidly evolving organisms, genomes
can reveal their detailed spatiotemporal spread. Such phylodynamic analyses are
particularly useful to understand the epidemiology of rapidly evolving viral
pathogens. As the number of genome sequences available for different pathogens
has increased dramatically over the last years, phylodynamic analysis with
traditional methods becomes challenging as these methods scale poorly with
growing datasets. Here, we present TreeTime, a Python-based framework for
phylodynamic analysis using an approximate Maximum Likelihood approach. TreeTime
can estimate ancestral states, infer evolution models, reroot trees to maximize
temporal signals, estimate molecular clock phylogenies and population size
histories. The runtime of TreeTime scales linearly with dataset size.
PMID- 29340211
TI - Differences in adaptive dynamics determine the success of virus variants that
propagate together.
AB - Virus fitness is a complex parameter that results from the interaction of virus
specific characters (e.g. intracellular growth rate, adsorption rate, virion
extracellular stability, and tolerance to mutations) with others that depend on
the underlying fitness landscape and the internal structure of the whole
population. Individual mutants usually have lower fitness values than the complex
population from which they come from. When they are propagated and allowed to
attain large population sizes for a sufficiently long time, they approach
mutation-selection equilibrium with the concomitant fitness gains. The
optimization process follows dynamics that vary among viruses, likely due to
differences in any of the parameters that determine fitness values. As a
consequence, when different mutants spread together, the number of generations
experienced by each of them prior to co-propagation may determine its particular
fate. In this work we attempt a clarification of the effect of different levels
of population diversity in the outcome of competition dynamics. To this end, we
analyze the behavior of two mutants of the RNA bacteriophage Qbeta that co
propagate with the wild-type virus. When both competitor viruses are clonal, the
mutants rapidly outcompete the wild type. However, the outcome in competitions
performed with partially optimized virus populations depends on the distance of
the competitors to their clonal origin. We also implement a theoretical
population dynamics model that describes the evolution of a heterogeneous
population of individuals, each characterized by a fitness value, subjected to
subsequent cycles of replication and mutation. The experimental results are
explained in the framework of our theoretical model under two non-excluding,
likely complementary assumptions: (1) The relative advantage of both competitors
changes as populations approach mutation-selection equilibrium, as a consequence
of differences in their growth rates and (2) one of the competitors is more
robust to mutations than the other. The main conclusion is that the nearness of
an RNA virus population to mutation-selection equilibrium is a key factor
determining the fate of particular mutants arising during replication.
PMID- 29340209
TI - Discovery of Culex pipiens associated tunisia virus: a new ssRNA(+) virus
representing a new insect associated virus family.
AB - In the global context of arboviral emergence, deep sequencing unlocks the
discovery of new mosquito-borne viruses. Mosquitoes of the species Culex pipiens,
C. torrentium, and C. hortensis were sampled from 22 locations worldwide for
transcriptomic analyses. A virus discovery pipeline was used to analyze the
dataset of 0.7 billion reads comprising 22 individual transcriptomes. Two closely
related 6.8 kb viral genomes were identified in C. pipiens and named as Culex
pipiens associated tunisia virus (CpATV) strains Ayed and Jedaida. The CpATV
genome contained four ORFs. ORF1 possessed helicase and RNA-dependent RNA
polymerase (RdRp) domains related to new viral sequences recently found mainly in
dipterans. ORF2 and 4 contained a capsid protein domain showing strong homology
with Virgaviridae plant viruses. ORF3 displayed similarities with eukaryotic
Rhoptry domain and a merozoite surface protein (MSP7) domain only found in
mosquito-transmitted Plasmodium, suggesting possible interactions between CpATV
and vertebrate cells. Estimation of a strong purifying selection exerted on each
ORFs and the presence of a polymorphism maintained in the coding region of ORF3
suggested that both CpATV sequences are genuine functional viruses. CpATV is part
of an entirely new and highly diversified group of viruses recently found in
insects, and that bears the genomic hallmarks of a new viral family.
PMID- 29340212
TI - 40 Years without Smallpox.
AB - The last case of natural smallpox was recorded in October, 1977. It took humanity
almost 20 years to achieve that feat after the World Health Organization had
approved the global smallpox eradication program. Vaccination against smallpox
was abolished, and, during the past 40 years, the human population has managed to
lose immunity not only to smallpox, but to other zoonotic orthopoxvirus
infections as well. As a result, multiple outbreaks of orthopoxvirus infections
in humans in several continents have been reported over the past decades. The
threat of smallpox reemergence as a result of evolutionary transformations of
these zoonotic orthopoxviruses exists. Modern techniques for the diagnostics,
prevention, and therapy of smallpox and other orthopoxvirus infections are being
developed today.
PMID- 29340213
TI - Non-Coding RNAs As Transcriptional Regulators In Eukaryotes.
AB - Non-coding RNAs up to 1,000 nucleotides in length are widespread in eukaryotes
and fulfil various regulatory functions, in particular during chromatin
remodeling and cell proliferation. These RNAs are not translated into proteins:
thus, they are non-coding RNAs (ncRNAs). The present review describes the
eukaryotic ncRNAs involved in transcription regulation, first and foremost,
targeting RNA polymerase II (RNAP II) and/or its major proteinaceous
transcription factors. The current state of knowledge concerning the regulatory
functions of SRA and TAR RNA, 7SK and U1 snRNA, GAS5 and DHFR RNA is summarized
herein. Special attention is given to murine B1 and B2 RNAs and human Alu RNA,
due to their ability to bind the active site of RNAP II. Discovery of bacterial
analogs of the eukaryotic small ncRNAs involved in transcription regulation, such
as 6S RNAs, suggests that they possess a common evolutionary origin.
PMID- 29340214
TI - The Contribution of Ribosomal Protein S1 to the Structure and Function of Qbeta
Replicase.
AB - The high resolution crystal structure of bacterial ribosome was determined more
than 10 years ago; however, it contains no information on the structure of the
largest ribosomal protein, S1. This unusual protein comprises six flexibly linked
domains; therefore, it lacks a fixed structure and this prevents the formation of
crystals. Besides being a component of the ribosome, protein S1 also serves as
one of the four subunits of Qbeta replicase, the RNA-directed RNA polymerase of
bacteriophage Qbeta. In each case, the role of this RNA-binding protein has been
thought to consist in holding the template close to the active site of the
enzyme. In recent years, a breakthrough was made in studies of protein S1 within
Qbeta replicase. This includes the discovery of its paradoxical ability to
displace RNA from the replicase complex and determining the crystal structure of
its fragment capable of performing this function. The new findings call for a re
examination of the contribution of protein S1 to the structure and function of
the ribosome.
PMID- 29340215
TI - Genome Stability Maintenance in Naked Mole-Rat.
AB - The naked mole-rat (Heterocephalus glaber) is one of the most promising models
used to study genome maintenance systems, including the effective repair of
damage to DNA. The naked mole-rat is the longest lived rodent species, which is
extraordinarily resistant to cancer and has a number of other unique phenotypic
traits. For at least 80% of its lifespan, this animal shows no signs of aging or
any increased likelihood of death and retains the ability to reproduce. The naked
mole-rat draws the heightened attention of researchers who study the molecular
basis of lengthy lifespan and cancer resistance. Despite the fact that the naked
mole-rat lives under genotoxic stress conditions (oxidative, etc.), the main
characteristics of its genome and proteome are a high stability and effective
functioning. Replicative senescence in the somatic cells of naked mole-rats is
missing, while an additional p53/pRb-dependent mechanism of early contact
inhibition has been revealed in its fibroblasts, which controls cell
proliferation and its mechanism of arf-dependent aging. The unique traits of
phenotypic and molecular adaptations found in the naked mole-rat speak to a high
stability and effective functioning of the molecular machinery that counteract
damage accumulation in its genome. This review analyzes existing results in the
study of the molecular basis of longevity and high cancer resistance in naked
mole-rats.
PMID- 29340217
TI - Translational Cross-Activation of the Encapsidated RNA of Potexviruses.
AB - We had shown the genomic RNA of potexviruses potato virus X and the alternanthera
mosaic virus to be inaccessible in vitro to ribosomes while in intact virion
form, but the RNAs can be translationally activated following the binding of
movement protein 1 (MP1) to virus particles. Here, we present the results of the
follow-up study targeting two more potexvirus species - the Narcissus mosaic
virus and the Potato aucuba mosaic virus. We found encapsidated potexviral RNA to
share common translational features in vitro and the MP1 to be potent over
homological virions of its "own" species and over heterological virions of other
species, as well exhibiting selective specificity. Reciprocal cross-activation is
observed among viral species phylogenetically either close or distant. There is
direct evidence that MP1 binding to the end of the virion is necessary, but not
sufficient, for translational activation of encapsidated RNA.
PMID- 29340218
TI - Synthesis and Characterization of Hybrid Core-Shell Fe3O4/SiO2 Nanoparticles for
Biomedical Applications.
AB - The creation of markers that provide both visual and quantitative information is
of considerable importance for the mapping of tissue macrophages and other cells.
We synthesized magnetic and magneto-fluorescent nanomarkers for the labeling of
cells which can be detected with high sensitivity by the magnetic particle
quantification (MPQ) technique. For stabilization under physiological conditions,
the markers were coated with a dense silica shell. In this case, the size and
zeta-potential of nanoparticles were controlled by a modified Stober reaction.
Also, we developed a novel facile two-step synthesis of carboxylic acid
functionalized magnetic SiO2 nanoparticles, with a carboxyl polymer shell forming
on the nanoparticles before the initiation of the Stober reaction. We extensively
characterized the nanomarkers by transmission electron microscopy, electron
microdiffraction, and dynamic and electrophoretic light scattering. We also
studied the nanoparticle cellular uptake by various eukaryotic cell lines.
PMID- 29340216
TI - Super-Resolution Microscopy in Studying the Structure and Function of the Cell
Nucleus.
AB - In recent decades, novel microscopic methods commonly referred to as super-
resolution microscopy have been developed. These methods enable the visualization
of a cell with a resolution of up to 10 nm. The application of these methods is
of great interest in studying the structure and function of the cell nucleus. The
review describes the main achievements in this field.
PMID- 29340219
TI - A Novel Hybrid Promoter ARE-hTERT for Cancer Gene Therapy.
AB - describe a novel hybrid tumor-specific promoter, ARE-hTERT, composed of the human
TERT gene promoter (hTERT) and the antioxidant response element (ARE) from the
human GCLM gene promoter. The hybrid promoter retains the tumor specificity of
the basal hTERT promoter but is characterized by an enhanced transcriptional
activity in cancer cells with abnormal activation of the Nrf2 transcription
factor and upon induction of oxidative stress. In the in vitro enzyme-prodrug
cancer gene therapy scheme, ARE-hTERT promoter-driven expression of CD : UPRT
(yeast cytosine deaminase : uracil phosphoribosyltransferase) chimeric protein
induced a more pronounced death of cancer cells either upon treatment with 5
fluorouracil (5FC) alone or when 5FC was combined with chemotherapeutic drugs as
compared to the hTERT promoter. The developed hybrid promoter can be considered a
better alternative to the hTERT promoter in cancer gene therapy schemes.
PMID- 29340220
TI - Multilocus Analysis of Genetic Susceptibility to Myocardial Infarction in
Russians: Replication Study.
AB - In search of genetic markers of myocardial infarction (MI) risk, which have
prognostic significance for Russians, we performed a replication study of MI
association with genetic variants of PCSK9 (rs562556), APOE (epsilon
polymorphism, rs7412 and rs429358), LPL (rs320), MTHFR (rs1801133), eNOS
(rs2070744), and the 9p21 region (rs1333049) in 405 patients with MI and 198
controls. Significant MI association was observed with variants of the lipid
metabolism genes (PCSK9, APOE and LPL), and of eNOS. The SNPs in the MTHFR gene
and the 9p21 region were not significantly associated with MI one by one but were
included in several different MI-associated allelic combinations identified by
multilocus analysis. Since we have not revealed nonlinear epistatic interactions
between the components of the identified combinations, we postulate that the
cumulative effect of genes that form a combination arises from the summation of
their small independent contributions. The prognostic significance of the
additive composite model built from the PCSK9, APOE, LPL, and eNOS genes as
genetic markers was assessed using ROC analysis. After we included these markers
in the previously published composite model of individual genetic risk of MI, the
prognostic efficacy in our sample reached AUC = 0.676. However, the results
obtained in this study certainly need to be replicated in an independent sample
of Russians.
PMID- 29340221
TI - Recombinant Antibodies to the Ebola Virus Glycoprotein.
AB - Currently, there are no approved therapies for targeted prevention and treatment
of Ebola hemorrhagic fever. In the present work, we describe the development of a
eukaryotic expression system for the production of three full-length chimeric
antibodies (IgG1-kappa isotypes) GPE118, GPE325, and GPE534 to the recombinant
glycoprotein of the Ebola virus (EBOV GP), which is a key factor in the
pathogenicity of the disease. The immunochemical properties of the obtained
antibodies were studied by immunoblotting and indirect, direct, and competitive
ELISA using the recombinant EBOV proteins rGPdTM, NP, and VP40. The authenticity
of the antibodies and the absence of cross-specificity with respect to the
structural proteins NP and VP40 of the Ebola virus were proved. The epitope
specificity of the resulting recombinant antibodies was studied using commercial
neutralizing antibodies against the viral glycoprotein. The recombinant
antibodies GPE118, GPE325, and GPE534 were shown to recognize glycoprotein
epitopes that coincide or overlap with the epitopes of three well-studied
neutralizing anti-Ebola virus antibodies.
PMID- 29340222
TI - Direct Molecular Fishing of New Protein Partners for Human Thromboxane Synthase.
AB - Thromboxane synthase (TBXAS1) catalyzes the isomerization reaction of
prostaglandin H2 producing thromboxane A2, the autocrine and paracrine factor in
many cell types. A high activity and metastability by these arachidonic acid
derivatives suggests the existence of supramolecular structures that are involved
in the regulation of the biosynthesis and directed translocation of thromboxane
to the receptor. The objective of this study was to identify TBXAS1 protein
partners from human liver tissue lysate using a complex approach based on the
direct molecular fishing technique, LC-MS/MS protein identification, and protein
protein interaction validation by surface plasmon resonance (SPR). As a result,
12 potential TBXAS1 protein partners were identified, including the components
regulating cytoskeleton organization (BBIP1 and ANKMY1), components of the
coagulation cascade of human blood (SERPINA1, SERPINA3, APOH, FGA, and FN1), and
the enzyme involved in the metabolism of xenobiotics and endogenous bioregulators
(CYP2E1). SPR validation on the Biacore 3000 biosensor confirmed the
effectiveness of the interaction between CYP2E1 (the enzyme that converts
prostaglandin H2 to 12-HHT/thromboxane A2 proantagonist) and TBXAS1 (Kd = (4.3 +/
0.4) * 10-7 M). Importantly, the TBXAS1*CYP2E1 complex formation increases
fivefold in the presence of isatin (indole-2,3-dione, a low-molecular nonpeptide
endogenous bioregulator, a product of CYP2E1). These results suggest that the
interaction between these hemoproteins is important in the regulation of the
biosynthesis of eicosanoids.
PMID- 29340223
TI - YABBY3-Orthologous Genes in Wild Tomato Species: Structure, Variability, and
Expression.
AB - Evolution of the genes encoding YABBY transcription factors is believed to be one
of the key reasons for flat leaf emergence from the radially symmetrical stem and
gynoecium diversity. YABBY genes determine the identity of the abaxial surface of
all aboveground lateral organs in seed plants. In the present study, complete
sequences of YABBY3-orthologous genes were identified and characterized in 13
accessions of cultivated and wild tomato species with diverse morphophysiology of
leaves, flowers, and fruits. The obtained gene sequences showed high homology (95
99%) and an identical exon-intron structure with the known S. lycopersicum YABBY3
gene, and they contained sequences that encode the conserved HMG-like YABBY and
Cys2Cys2-zinc-finger domains. In total, in the analyzed YABBY3 genes, 317
variable sites were found, wherein 8 of 24 exon-specific SNPs were nonsynonymous.
In the vegetative and reproductive organs of red-fruited and green-fruited tomato
species, YABBY3 gene expression was similar to that in S. pimpinellifolium
described earlier, but it demonstrated interspecies differences at the leaf-, bud
and flower-specific expression levels.
PMID- 29340224
TI - CaMKII Is Involved in the Choline-Induced Downregulation of Acetylcholine Release
in Mouse Motor Synapses.
AB - We investigated the involvement of calcium-dependent enzymes, protein kinase C
(PKC) and calcium-calmodulin-dependent protein kinase II (CaMKII), in the
signaling pathway triggered by the activation of presynaptic alpha7-type
nicotinic acetylcholine receptors by exogenous choline, leading to downregulation
of the evoked acetylcholine (ACh) release in mouse motor synapses. Blockade of
PKC with chelerythrine neither changed the evoked release of ACh by itself nor
prevented the inhibitory effect of choline. The CaMKII blocker KN-62 did not
affect synaptic activity but fully prevented the choline-induced downregulation
of ACh release.
PMID- 29340225
TI - Effects of Calcium on Drinking Fluorosis-induced Hippocampal Synaptic Plasticity
Impairment in the Offspring of Rats.
AB - Objective: This study investigated the effects of calcium on fluorosis-induced
impairment in learning and memory of offspring rats. Methods Seventy-five newly
weaned female Sprague-Dawley (SD) rats were randomly divided into five groups as
follows: Control group (Control) drank tap water, and ate the normal diet
(calcium content of 0.79%); fluoride group (F) drank 100 mg/L NaF solution, and
ate the normal diet; low calcium group (LCa) drank tap water, and ate the low
calcium diet (calcium content of 0.063%); low calcium fluoride group (F+LCa)
drank 100 mg/L NaF solution, and ate the low calcium diet; high calcium fluoride
group (F+HCa) drank 100 mg/L NaF solution, and ate the high calcium diet (calcium
content of 7%). After exposing rats to fluoride for three months, male and female
rats were mated and 14 and 28 days old offspring were obtained as experimental
subjects. Examinations determined the submicroscopic parameters of the synaptic
interface and expression levels of specific proteins: doublecortin (DCX) and
synaptophysin (p38). Results: (1) High fluorosis significantly reduced synapse
density, length of synaptic active zone, thickness of postsynaptic density, and
led to abnormal changes in the structural parameter of synaptic gap width, which
was significantly reduced or increased. High dietary calcium significantly
reversed the abnormal changes in structural parameters, and low calcium
aggravated these variations. (2) Dietary calcium resulted in nonsignificant
effect on expression levels of DCX and p38. Conclusion: The results suggested
that dietary calcium significantly affected hippocampal synaptic plasticity of
offspring of mothers exposed to water fluorosis, but its molecular mechanism may
not be related to the expression of DCX and p38 in the brain. The findings also
demonstrate the important effects of maternal exposure to water fluorosis on
offspring brain functions before water improvement.
PMID- 29340226
TI - Depression is Associated with CRP SNPs in Patients with Family History.
AB - Objective: The pathogenesis of depression is not fully understood, but studies
have suggested that higher circulating levels of C reactive protein (CRP) might
relate to depression occurrence. However, due to the highly variability of
individual patients' conditions, the results to date are inconsistent.
Considering Single nucleotide polymorphisms (SNPs) of CRP gene have also been
suggested to predict plasma CRP levels. In the present study, we hypothesize that
inherited CRP allelic variations may co-vary with depressive symptomatology.
Methods: We recruited patients with a diagnosis of depression, with or without
family depression history. We then detected serum CRP levels, as well as genome
CRP SNPs from participants of this project. Results: We found a significantly
higher circulating CRP levels in patients with a positive family history.
Furthermore, we also identified certain inherited CRP SNPs (A allele in rs1417938
and C allele in rs1205) which could up-regulate serum CRP levels and thus be
associated with depression occurrence. Conclusion: Our findings raise new
evidence for the relationship between circulating CRP level and depression
occurrence.
PMID- 29340227
TI - Keyhole Surgery of Pineal Area Tumors - Personal Experience in 22 Patients.
AB - Background: Pineal area tumors are challenging for surgery due to their location.
However, the removal of the lesion is critical for further treatment and survival
of the patients. Material and methods: 22 patients with pineal area tumors were
surgically treated via keyhole medial suboccipital craniotomy and supracerebellar
midline approach All the patients were operated in the sitting position with the
use of operating microscope and microsurgical technique. Results: All patients
survived surgery in a perfect condition, and no one patient worsened after
surgery. No complications due to the sitting position were noted. Conclusions:
Surgical removal of pineal area tumors via small suboccipital craniotomy is safe
and with the use of microsurgical techniques the results of surgical treatment
are excellent. The sitting position of the patients gives a better view to the
surgeon. We did not observe any intraoperational complications due to the sitting
position.
PMID- 29340228
TI - A new small-bodied ornithopod (Dinosauria, Ornithischia) from a deep, high-energy
Early Cretaceous river of the Australian-Antarctic rift system.
AB - A new small-bodied ornithopod dinosaur, Diluvicursor pickeringi, gen. et sp.
nov., is named from the lower Albian of the Eumeralla Formation in southeastern
Australia and helps shed new light on the anatomy and diversity of Gondwanan
ornithopods. Comprising an almost complete tail and partial lower right hindlimb,
the holotype (NMV P221080) was deposited as a carcass or body-part in a log
filled scour near the base of a deep, high-energy river that incised a faunally
rich, substantially forested riverine floodplain within the Australian-Antarctic
rift graben. The deposit is termed the 'Eric the Red West Sandstone.' The
holotype, interpreted as an older juvenile ~1.2 m in total length, appears to
have endured antemortem trauma to the pes. A referred, isolated posterior caudal
vertebra (NMV P229456) from the holotype locality, suggests D. pickeringi grew to
at least 2.3 m in length. D. pickeringi is characterised by 10 potential
autapomorphies, among which dorsoventrally low neural arches and transversely
broad caudal ribs on the anterior-most caudal vertebrae are a visually defining
combination of features. These features suggest D. pickeringi had robust anterior
caudal musculature and strong locomotor abilities. Another isolated anterior
caudal vertebra (NMV P228342) from the same deposit, suggests that the fossil
assemblage hosts at least two ornithopod taxa. D. pickeringi and two
stratigraphically younger, indeterminate Eumeralla Formation ornithopods from
Dinosaur Cove, NMV P185992/P185993 and NMV P186047, are closely related. However,
the tail of D. pickeringi is far shorter than that of NMV P185992/P185993 and its
pes more robust than that of NMV P186047. Preliminary cladistic analysis,
utilising three existing datasets, failed to resolve D. pickeringi beyond a large
polytomy of Ornithopoda. However, qualitative assessment of shared anatomical
features suggest that the Eumeralla Formation ornithopods, South American
Anabisetia saldiviai and Gasparinisaura cincosaltensis, Afro-Laurasian
dryosaurids and possibly Antarctic Morrosaurus antarcticus share a close
phylogenetic progenitor. Future phylogenetic analysis with improved data on
Australian ornithopods will help to test these suggested affinities.
PMID- 29340229
TI - Acquired melanocytic naevus phenotypes and MC1R genotypes in Han Chinese: a cross
sectional study.
AB - Background: Early detection and treatment are the most important elements in
reducing the incidence of melanoma deaths. Acquired melanocytic naevi (AMN) are
well-known precursors of melanoma but most of our knowledge on the clinico
dermoscopic phenotypes of AMN is based on studies in European-background
populations, particularly American and Australian populations. There has been
little research in Chinese Han populations on clinico-dermoscopic variability of
naevi or how naevi are affected by melanoma-linked variants of the melanocortin 1
receptor (MC1R) gene. Methods: Clinical and dermoscopic features of 448 AMN in
115 patients from the Han ethnic group in mainland China were described. Germline
polymorphisms in MC1R were determined for 98 of these patients. Results: AMN were
predominantly found on the head and neck. Dermoscopic patterns observed were
nonspecific, reticular, globular, and parallel furrow, with most AMN having a
nonspecific pattern. There were no associations between MC1R polymorphisms and
clinical or dermoscopic features of AMN. Discussion: Our results provide evidence
that AMN in the Han population in China have similar dermoscopic patterns to
those in European populations, but are present in much lower numbers. As there
were no associations between clinical or dermoscopic features of AMN and MC1R
polymorphisms, further studies should focus on candidate gene associations with
AMN features and the risk of melanoma, with larger sample sizes and comparisons
to AMN in other populations.
PMID- 29340230
TI - Arbutin increases Caenorhabditis elegans longevity and stress resistance.
AB - Arbutin (p-hydroxyphenyl-beta-D-glucopyranoside), a well-known tyrosinase
inhibitor, has been widely used as a cosmetic whitening agent. Although its
natural role is to scavenge free radicals within cells, it has also exhibited
useful activities for the treatment of diuresis, bacterial infections and cancer,
as well as anti-inflammatory and anti-tussive activities. Because function of
free radical scavenging is also related to antioxidant and the effects of arbutin
on longevity and stress resistance in animals have not yet been confirmed, here
the effects of arbutin on Caenorhabditis elegans were investigated. The results
demonstrated that optimal concentrations of arbutin could extend lifespan and
enhance resistance to oxidative stress. The underlying molecular mechanism for
these effects involves decreased levels of reactive oxygen species (ROS),
improvement of daf-16 nuclear localization, and up-regulated expression of daf-16
and its downstream targets, including sod-3 and hsp16.2. In this work the roles
of arbutin in lifespan and health are studied and the results support that
arbutin is an antioxidant for maintaining overall health.
PMID- 29340232
TI - The effects of arbuscular mycorrhizal fungi and root interaction on the
competition between Trifolium repens and Lolium perenne.
AB - Understanding the factors that alter competitive interactions and coexistence
between plants is a key issue in ecological research. A pot experiment was
conducted to test the effects of root interaction and arbuscular mycorrhizal
fungi (AMF) inoculation on the interspecies competition between Trifolium repens
and Lolium perenne under different proportions of mixed sowing by the combination
treatment of two levels of AMF inoculation (inoculation and non-inoculation) and
two levels of root interaction (root interaction and non-root interaction).
Overall, the aboveground and belowground biomass of T. repens and L. perenne were
not altered by AMF inoculation across planting ratios, probably because the
fertile soil reduced the positive effect of AMF on plant growth. Both inter- and
intraspecies root interaction significantly decreased the aboveground biomass of
T. repens, but tended to increase the aboveground biomass of L. perenne across
planting ratios, and thus peaked at the 4:4 polyculture. These results showed
that T. repens competed poorly with L. perenne because of inter and intraspecies
root interaction. Our results indicate that interspecies root interaction
regulates the competitive ability of grass L. perenne and legume T. repens in
mixtures and further makes great contribution for overyielding. Furthermore, AMF
may not be involved in plant-plant interaction in fertile condition.
PMID- 29340231
TI - ksrMKL: a novel method for identification of kinase-substrate relationships using
multiple kernel learning.
AB - Phosphorylation exerts a crucial role in multiple biological cellular processes
which is catalyzed by protein kinases and closely related to many diseases.
Identification of kinase-substrate relationships is important for understanding
phosphorylation and provides a fundamental basis for further disease-related
research and drug design. In this study, we develop a novel computational method
to identify kinase-substrate relationships based on multiple kernel learning. The
comparative analysis is based on a 10-fold cross-validation process and the
dataset collected from the Phospho.ELM database. The results show that ksrMKL is
greatly improved in various measures when compared with the single kernel support
vector machine. Furthermore, with an independent test dataset extracted from the
PhosphoSitePlus database, we compare ksrMKL with two existing kinase-substrate
relationship prediction tools, namely iGPS and PKIS. The experimental results
show that ksrMKL has better prediction performance than these existing tools.
PMID- 29340233
TI - Crustacean amphipods from marsh ponds: a nutritious feed resource with potential
for application in Integrated Multi-Trophic Aquaculture.
AB - Coastal protection, nutrient cycling, erosion control, water purification, and
carbon sequestration are ecosystem services provided by salt marshes.
Additionally, salt ponds offer coastal breeding and a nursery habitat for fishes
and they provide abundant invertebrates, such as amphipods, which are potentially
useful as a resource in aquaculture. Fishmeal and fish oil are necessary food
resources to support aquaculture of carnivorous species due to their omega-3 long
chain polyunsaturated fatty acids (n-3 LC-PUFA). Currently, aquaculture depends
on limited fisheries and feed with elevated n-3 LC-PUFA levels, but the
development of more sustainable food sources is necessary. Amphipods appear to be
a potential high quality alternative feed resource for aquaculture. Hence, a
nutritional study was carried out for several main amphipod species-Microdeutopus
gryllotalpa, Monocorophium acherusicum, Gammarus insensibilis, Melita palmata and
Cymadusa filosa-in terrestrial ponds in the South of Spain. These species showed
high protein content (up to 40%), high n-3 PUFA and phospholipid levels, and high
levels of phophatidylcholine (PC), phosphatidylethanolamine (PE) and
triacylglycerols (TAG), the latter being significantly high for M. acherusicum.
M. gryllotalpa and M. acherusicum showed the highest proportion of lipids (19.15%
and 18.35%, respectively). Isoleucine, glycine and alanine were the dominant
amino acids in all species. In addition, amphipods collected from ponds showed
low levels of heavy metals. Furthermore, the biochemical profiles of the five
species of amphipods have been compared with other studied alternative prey.
Therefore, pond amphipods are good candidates to be used as feed, and are
proposed as a new sustainable economic resource to be used in aquaculture. G.
insensibilis may be the best for intensive culture as an alternative feed
resource because it shows: (1) adequate n-3 PUFA and PL composition; (2) high
levels of glycine, alanine, tyrosine, isoleucine and lysine; (3) high natural
densities; (4) large body size (>=1 cm), and (5) high concentration of calcium.
Moreover, a combined culture of amphipods and fishes in these marsh ponds seems a
promising and environmentally sustainable way to develop Integrate Multi-Trophic
Aquaculture (IMTA) in these ecosystems.
PMID- 29340234
TI - Achilles heel of a powerful invader: restrictions on distribution and
disappearance of feral pigs from a protected area in Northern Pantanal, Western
Brazil.
AB - This paper focuses on a rare case of natural disappearance of feral pigs (Sus
scrofa) in an extensive area without using traditional methods of eradication
programs. The study was conducted both in the Private Reserve of Natural Heritage
(PRNH) Sesc Pantanal and in an adjacent traditional private cattle ranch. In
1998, feral pigs were abundant and widely distributed in the PRNH. However, the
feral pigs gradually disappeared from the area and currently, the absence of pigs
in the PRNH contrasts with the adjacent cattle ranch where the species is
abundant. To understand the current distribution of the species in the region we
partitioned the effects of variation of feral pigs' presence considering the
habitat structure (local), landscape composition and the occurrence of potential
predators. Additionally, we modeled the distributions of the species in Northern
Pantanal, projecting into the past using the classes of vegetation cover before
the PRNH implementation (year 1988). Our results show areas with more suitability
for feral pigs in regions where the landscape is dominated by pastures and
permeated by patches of Seasonal Dry Forest. The species tends to avoid
predominantly forested areas. Additionally, we recorded that the environmental
suitability decreases exponentially as the distance from water bodies increases.
The disappearance of feral pigs in the PRNH area seems to be associated with
changes in the landscape and vegetation structure after the removal of the
cattle. In the Brazilian Pantanal, the feral pigs' occurrence seems strongly
conditioned to environmental changes associated to livestock activity.
PMID- 29340235
TI - Evidence-based design and evaluation of a whole genome sequencing clinical report
for the reference microbiology laboratory.
AB - Background: Microbial genome sequencing is now being routinely used in many
clinical and public health laboratories. Understanding how to report complex
genomic test results to stakeholders who may have varying familiarity with
genomics-including clinicians, laboratorians, epidemiologists, and researchers-is
critical to the successful and sustainable implementation of this new technology;
however, there are no evidence-based guidelines for designing such a report in
the pathogen genomics domain. Here, we describe an iterative, human-centered
approach to creating a report template for communicating tuberculosis (TB)
genomic test results. Methods: We used Design Study Methodology-a human centered
approach drawn from the information visualization domain-to redesign an existing
clinical report. We used expert consults and an online questionnaire to discover
various stakeholders' needs around the types of data and tasks related to TB that
they encounter in their daily workflow. We also evaluated their perceptions of
and familiarity with genomic data, as well as its utility at various clinical
decision points. These data shaped the design of multiple prototype reports that
were compared against the existing report through a second online survey, with
the resulting qualitative and quantitative data informing the final, redesigned,
report. Results: We recruited 78 participants, 65 of whom were clinicians,
nurses, laboratorians, researchers, and epidemiologists involved in TB diagnosis,
treatment, and/or surveillance. Our first survey indicated that participants were
largely enthusiastic about genomic data, with the majority agreeing on its
utility for certain TB diagnosis and treatment tasks and many reporting some
confidence in their ability to interpret this type of data (between 58.8% and
94.1%, depending on the specific data type). When we compared our four prototype
reports against the existing design, we found that for the majority (86.7%) of
design comparisons, participants preferred the alternative prototype designs over
the existing version, and that both clinicians and non-clinicians expressed
similar design preferences. Participants showed clearer design preferences when
asked to compare individual design elements versus entire reports. Both the
quantitative and qualitative data informed the design of a revised report,
available online as a LaTeX template. Conclusions: We show how a human-centered
design approach integrating quantitative and qualitative feedback can be used to
design an alternative report for representing complex microbial genomic data. We
suggest experimental and design guidelines to inform future design studies in the
bioinformatics and microbial genomics domains, and suggest that this type of
mixed-methods study is important to facilitate the successful translation of
pathogen genomics in the clinic, not only for clinical reports but also more
complex bioinformatics data visualization software.
PMID- 29340236
TI - DNA barcode-based survey of Trichoptera in the Crooked River reveals three new
species records for British Columbia.
AB - Anthropogenic pressures on aquatic systems have placed a renewed focus on
biodiversity of aquatic macroinvertebrates. By combining classical taxonomy and
DNA barcoding we identified 39 species of caddisflies from the Crooked River, a
unique and sensitive system in the southernmost arctic watershed in British
Columbia. Our records include three species never before recorded in British
Columbia: Lepidostoma togatum (Lepidostomatidae), Ceraclea annulicornis
(Leptoceridae), and possibly Cheumatopsyche harwoodi (Hydropsychidae). Three
other specimens may represent new occurrence records and a number of other
records seem to be substantial observed geographic range expansions within
British Columbia.
PMID- 29340237
TI - Using underwater video to evaluate the performance of the Fukui trap as a
mitigation tool for the invasive European green crab (Carcinus maenas) in
Newfoundland, Canada.
AB - The European green crab (Carcinus maenas) is a destructive marine invader that
was first discovered in Newfoundland waters in 2007 and has since become
established in nearshore ecosystems on the south and west coast of the island.
Targeted fishing programs aimed at removing green crabs from invaded Newfoundland
ecosystems use Fukui traps, but the capture efficiency of these traps has not
been previously assessed. We assessed Fukui traps using in situ observation with
underwater video cameras as they actively fished for green crabs. From these
videos, we recorded the number of green crabs that approached the trap, the
outcome of each entry attempt (success or failure), and the number of exits from
the trap. Across eight videos, we observed 1,226 green crab entry attempts, with
only a 16% rate of success from these attempts. Based on these observations we
believe there is scope to improve the performance of the Fukui trap through
modifications in order to achieve a higher catch per unit effort (CPUE),
maximizing trap usage for mitigation. Ultimately, a more efficient Fukui trap
will help to control green crab populations in order to preserve the function and
integrity of ecosystems invaded by the green crab.
PMID- 29340238
TI - A revised cranial description of Massospondylus carinatus Owen (Dinosauria:
Sauropodomorpha) based on computed tomographic scans and a review of cranial
characters for basal Sauropodomorpha.
AB - Massospondylus carinatus is a basal sauropodomorph dinosaur from the early
Jurassic Elliot Formation of South Africa. It is one of the best-represented
fossil dinosaur taxa, known from hundreds of specimens including at least 13
complete or nearly complete skulls. Surprisingly, the internal cranial anatomy of
M. carinatus has never been described using computed tomography (CT) methods.
Using CT scans and 3D digital representations, we digitally reconstruct the bones
of the facial skeleton, braincase, and palate of a complete, undistorted cranium
of M. carinatus (BP/1/5241). We describe the anatomical features of the cranial
bones, and compare them to other closely related sauropodomorph taxa such as
Plateosaurus erlenbergiensis, Lufengosaurus huenei, Sarahsaurus aurifontanalis
and Efraasia minor. We identify a suite of character states of the skull and
braincase for M. carinatus that sets it apart from other taxa, but these remain
tentative due to the lack of comparative sauropodomorph braincase descriptions in
the literature. Furthermore, we hypothesize 27 new cranial characters useful for
determining relationships in non-sauropodan Sauropodomorpha, delete five pre
existing characters and revise the scores of several existing cranial characters
to make more explicit homology statements. All the characters that we
hypothesized or revised are illustrated. Using parsimony as an optimality
criterion, we then test the relationships of M. carinatus (using BP/1/5241 as a
specimen-level exemplar) in our revised phylogenetic data matrix.
PMID- 29340239
TI - FastViromeExplorer: a pipeline for virus and phage identification and abundance
profiling in metagenomics data.
AB - With the increase in the availability of metagenomic data generated by next
generation sequencing, there is an urgent need for fast and accurate tools for
identifying viruses in host-associated and environmental samples. In this paper,
we developed a stand-alone pipeline called FastViromeExplorer for the detection
and abundance quantification of viruses and phages in large metagenomic datasets
by performing rapid searches of virus and phage sequence databases. Both
simulated and real data from human microbiome and ocean environmental samples are
used to validate FastViromeExplorer as a reliable tool to quickly and accurately
identify viruses and their abundances in large datasets.
PMID- 29340240
TI - Refining amino acid hydrophobicity for dynamics simulation of membrane proteins.
AB - Coarse-grained (CG) models have been successful in simulating the chemical
properties of lipid bilayers, but accurate treatment of membrane proteins and
lipid-protein molecular interactions remains a challenge. The CgProt force field,
original developed with the multiscale coarse graining method, is assessed by
comparing the potentials of mean force for sidechain insertion in a DOPC bilayer
to results reported for atomistic molecular dynamics simulations. Reassignment of
select CG sidechain sites from the apolar to polar site type was found to improve
the attractive interfacial behavior of tyrosine, phenylalanine and asparagine as
well as charged lysine and arginine residues. The solvation energy at membrane
depths of 0, 1.3 and 1.7 nm correlates with experimental partition coefficients
in aqueous mixtures of cyclohexane, octanol and POPC, respectively, for sidechain
analogs and Wimley-White peptides. These experimental values serve as important
anchor points in choosing between alternate CG models based on their observed
permeation profiles, particularly for Arg, Lys and Gln residues where the all
atom OPLS solvation energy does not agree well with experiment. Available
partitioning data was also used to reparameterize the representation of the
peptide backbone, which needed to be made less attractive for the bilayer
hydrophobic core region. The newly developed force field, CgProt 2.4, correctly
predicts the global energy minimum in the potentials of mean force for insertion
of the uncharged membrane-associated peptides LS3 and WALP23. CgProt will find
application in studies of lipid-protein interactions and the conformational
properties of diverse membrane protein systems.
PMID- 29340241
TI - Risk factors for osteoporosis in male patients with chronic obstructive pulmonary
disease in Taiwan.
AB - Objective: To investigate the risk factors for osteoporosis in male Taiwanese
patients with chronic obstructive pulmonary disease (COPD). Methods: This cross
sectional study evaluated male COPD outpatients and age-matched male subjects at
a regional teaching hospital. The following data were obtained and analyzed: bone
mineral density of the lumbar spine and hip on dual-energy X-ray absorptiometry,
demographic characteristics, questionnaire interview results, pulmonary function
test results, chest posterior-anterior radiographic findings, and biochemical and
high-sensitivity C-reactive protein (hs-CRP) levels. Results: Fifty-nine male
COPD patients and 36 age-matched male subjects were enrolled. COPD patients had
lower body mass index (BMI) (23.6 +/- 4.1 vs. 25.2 +/- 3.0 kg/m2) and higher
total prevalence for osteoporosis and osteopenia than controls. Among COPD
patients, patients with osteoporosis had lower BMI, body weight, waist
circumference, and triglyceride level but higher hs-CRP level, and tended to have
lower creatinine level. Binary logistic regression analysis for factors including
age, BMI, creatinine, hs-CRP, smoking, steroid use, and forced expiratory volume
in one second (FEV1) revealed that an hs-CRP level >=5 and decreased creatinine
level were independent risk factors for osteoporosis in COPD patients. Lower BMI
tended to be associated with osteoporosis development, although it did not reach
statistical significance, and hs-CRP was associated with COPD severity and
steroid use history. Conclusion: The total prevalence of osteoporosis and
osteopenia in male Taiwanese COPD patients is higher than that in age-matched
male subjects and systemic inflammation is an independent risk factors for
osteoporosis. Low creatinine level in COPD patients should raise the suspicion of
sarcopenia and associated increased risk of osteoporosis.
PMID- 29340242
TI - A diagnostic model for minimal change disease based on biological parameters.
AB - Background: Minimal change disease (MCD) is a kind of nephrotic syndrome (NS). In
this study, we aimed to establish a mathematical diagnostic model based on
biological parameters to classify MCD. Methods: A total of 798 NS patients were
divided into MCD group and control group. The comparison of biological indicators
between two groups were performed with t-tests. Logistic regression was used to
establish the diagnostic model, and the diagnostic value of the model was
estimated using receiver operating characteristic (ROC) analysis. Results:
Thirteen indicators including Anti-phospholipase A2 receptor (anti-PLA2R) (P =
0.000), Total protein (TP) (P = 0.000), Albumin (ALB) (P = 0.000), Direct
bilirubin (DB) (P = 0.002), Creatinine (Cr) (P = 0.000), Total cholesterol (CH)
(P = 0.000), Lactate dehydrogenase (LDH) (P = 0.007), High density lipoprotein
cholesterol (HDL) (P = 0.000), Low density lipoprotein cholesterol (LDL) (P =
0.000), Thrombin time (TT) (P = 0.000), Plasma fibrinogen (FIB) (P = 0.000),
Immunoglobulin A (IgA) (P = 0.008) and Complement 3 (C3) (P = 0.019) were
significantly correlated with MCD. Furthermore, the area under ROC curves of CH,
HDL, LDL, TT and FIB were more than 0.70. Logistic analysis demonstrated that CH
and TT were risk factors for MCD. According to the ROC of "CH+TT", the AUC was
0.827, with the sensitivity of 83.0% and the specificity of 69.8% (P = 0.000).
Conclusion: The established diagnostic model with CH and TT could be used for
classified diagnosis of MCD.
PMID- 29340243
TI - Urban heat island effect on cicada densities in metropolitan Seoul.
AB - Background: Urban heat island (UHI) effect, the ubiquitous consequence of
urbanization, is considered to play a major role in population expansion of
numerous insects. Cryptotympana atrata and Hyalessa fuscata are the most abundant
cicada species in the Korean Peninsula, where their population densities are
higher in urban than in rural areas. We predicted a positive relationship between
the UHI intensities and population densities of these two cicada species in
metropolitan Seoul. Methods: To test this prediction, enumeration surveys of
cicada exuviae densities were conducted in 36 localities located within and in
the vicinity of metropolitan Seoul. Samples were collected in two consecutive
periods from July to August 2015. The abundance of each species was estimated by
two resource-weighted densities, one based on the total geographic area, and the
other on the total number of trees. Multiple linear regression analyses were
performed to identify factors critical for the prevalence of cicada species in
the urban habitat. Results: C. atrata and H. fuscata were major constituents of
cicada species composition collected across all localities. Minimum temperature
and sampling period were significant factors contributing to the variation in
densities of both species, whereas other environmental factors related to
urbanization were not significant. More cicada exuviae were collected in the
second rather than in the first samplings, which matched the phenological pattern
of cicadas in metropolitan Seoul. Cicada population densities increased
measurably with the increase in temperature. Age of residential complex also
exhibited a significantly positive correlation to H. fuscata densities, but not
to C. atrata densities. Discussion: Effects of temperature on cicada densities
have been discerned from other environmental factors, as cicada densities
increased measurably in tandem with elevated temperature. Several mechanisms may
contribute to the abundance of cicadas in urban environments, such as higher
fecundity of females, lower mortality rate of instars, decline in host plant
quality, and local adaptation of organisms, but none of them were tested in the
current study. Conclusions: In sum, results of the enumeration surveys of cicada
exuviae support the hypothesis that the UHI effect underlies the population
expansion of cicadas in metropolitan Seoul. Nevertheless, the underlying
mechanisms for this remain untested.
PMID- 29340244
TI - An exploratory study of adolescent response to fluoxetine using psychological and
biological predictors.
AB - Background: Not enough is known about predicting therapeutic response to
serotonin-specific reuptake inhibitors, and specifically to fluoxetine. This
exploratory study used psychological and biological markers for (retrospective)
prediction of treatment-response to fluoxetine in depressed and/or anxious
adolescents. Methods: Forty-one consecutive adolescent outpatients with a primary
diagnosis of severe affective and/or anxiety disorders were assessed and treated
with an open-label 8-week trial of fluoxetine. Type D personality was assessed
with the 14-item questionnaire, the DS14. In addition, TNFalpha, IL-6, and IL-1b
were measured pre- and post-treatment. Results: There was an elevation of Type D
personality in patients, compared to the adolescent population rate. Post
treatment, 44% of patients were classified as non-responders; the relative risk
of non-response for Type D personality patients was 2.8. Binary logistic
regression predicting response vs. non-response showed a contribution of initial
TNFalpha levels as well as Type D personality to non-response. Conclusions: In
this exploratory study, the most significant contributor to non-response was Type
D personality. However, the measurement of Type D was not prospective, and thus
may be confounded with psychiatric morbidity. The measurement of personality in
psychiatric settings may contribute to the understanding of treatment response
and have clinical utility.
PMID- 29340245
TI - Effects of the visual-feedback-based force platform training with functional
electric stimulation on the balance and prevention of falls in older adults: a
randomized controlled trial.
AB - Background: Force platform training with functional electric stimulation aimed at
improving balance may be effective in fall prevention for older adults. Aim of
the study is to evaluate the effects of the visual-feedback-based force platform
balance training with functional electric stimulation on balance and fall
prevention in older adults. Methods: A single-centre, unblinded, randomized
controlled trial was conducted. One hundred and twenty older adults were randomly
allocated to two groups: the control group (n = 60, one-leg standing balance
exercise, 12 min/d) or the intervention group (n = 60, force platform training
with functional electric stimulation, 12 min/d). The training was provided 15
days a month for 3 months by physical therapists. Medial-lateral and anterior
posterior maximal range of sway with eyes open and closed, the Berg Balance
Scale, the Barthel Index, the Falls Efficacy scale-International were assessed at
baseline and after the 3-month intervention. A fall diary was kept by each
participant during the 6-month follow-up. Results: On comparing the two groups,
the intervention group showed significantly decreased (p < 0.01) medial-lateral
and anterior-posterior maximal range of sway with eyes open and closed. There was
significantly higher improvement in the Berg Balance Scale (p < 0.05), the
Barthel Index (p < 0.05) and the Falls Efficacy Scale-International (p < 0.05),
along with significantly lesser number of injurious fallers (p < 0.05), number of
fallers (p < 0.05), and fall rates (p < 0.05) during the 6-month follow-up in the
intervention group. Conclusion: This study showed that the visual feedback-based
force platform training with functional electric stimulation improved balance and
prevented falls in older adults.
PMID- 29340246
TI - Stat-tracks and mediotypes: powerful tools for modern ichnology based on 3D
models.
AB - Vertebrate tracks are subject to a wide distribution of morphological types. A
single trackmaker may be associated with a range of tracks reflecting individual
pedal anatomy and behavioural kinematics mediated through substrate properties
which may vary both in space and time. Accordingly, the same trackmaker can leave
substantially different morphotypes something which must be considered in
creating ichnotaxa. In modern practice this is often captured by the collection
of a series of 3D track models. We introduce two concepts to help integrate these
3D models into ichnological analysis procedures. The mediotype is based on the
idea of using statistically-generated three-dimensional track models (median or
mean) of the type specimens to create a composite track to support formal
recognition of a ichno type. A representative track (mean and/or median) is
created from a set of individual reference tracks or from multiple examples from
one or more trackways. In contrast, stat-tracks refer to other digitally
generated tracks which may explore variance. For example, they are useful in:
understanding the preservation variability of a given track sample; identifying
characteristics or unusual track features; or simply as a quantitative comparison
tool. Both concepts assist in making ichnotaxonomical interpretations and we
argue that they should become part of the standard procedure when instituting new
ichnotaxa. As three-dimensional models start to become a standard in publications
on vertebrate ichnology, the mediotype and stat-track concepts have the potential
to help guiding a revolution in the study of vertebrate ichnology and
ichnotaxonomy.
PMID- 29340247
TI - Weekend effect in upper gastrointestinal bleeding: a systematic review and meta
analysis.
AB - Aim: To perform a systematic review and meta-analysis of the weekend effect on
the mortality of patients with upper gastrointestinal bleeding(UGIB). Methods:
The review protocol has been registered in the PROSPERO International Prospective
Register of Systematic Reviews (registration number: CRD42017073313) and was
written according to the Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA) statement. We conducted a search of the PUBMED, COCHRANE,
EMBASE and CINAHL databases from inception to August 2017. All observational
studies comparing mortality between UGIB patients with weekend versus weekday
admissions were included. Articles that were published only in abstract form or
not published in a peer-reviewed journal were excluded. The quality of articles
was assessed using the Newcastle-Ottawa Scale. We pooled results from the
articles using random-effect models. Heterogeneity was evaluated by the chi
square-based Q-test and I2 test. To address heterogeneity, we performed
sensitivity and subgroup analyses. Potential publication bias was assessed via
funnel plot. Results: Eighteen observational cohort studies involving 1,232,083
study patients were included. Weekend admission was associated with significantly
higher 30-day or in-hospital mortality in all studies (OR = 1.12, 95% CI [1.07
1.17], P < 0.00001). Increased in-hospital mortality was also associated with
weekend admission (OR = 1.12, 95% CI [1.08-1.17], P < 0.00001). No significant
difference in in-hospital mortality was observed between patients admitted with
variceal bleeding during the weekend or on weekdays (OR = 0.99, 95% CI [0.91
1.08], P = 0.82); however, weekend admission was associated with a 15% increase
in in-hospital mortality for patients with non-variceal bleeding (OR = 1.15, 95%
CI [1.09-1.21], P < 0.00001). The time to endoscopy for weekday admission was
significantly less than that obtained for weekend admission (MD = -2.50, 95% CI [
4.08--0.92], P = 0.002). Conclusions: The weekend effect is associated with
increased mortality of UGIB patients, particularly in non-variceal bleeding. The
timing of endoscopic intervention might be a factor that influences mortality of
UGIB patients.
PMID- 29340248
TI - Depth- and range-dependent variation in the performance of aquatic telemetry
systems: understanding and predicting the susceptibility of acoustic tag-receiver
pairs to close proximity detection interference.
AB - Background: Passive acoustic telemetry using coded transmitter tags and
stationary receivers is a popular method for tracking movements of aquatic
animals. Understanding the performance of these systems is important in array
design and in analysis. Close proximity detection interference (CPDI) is a
condition where receivers fail to reliably detect tag transmissions. CPDI
generally occurs when the tag and receiver are near one another in acoustically
reverberant settings. Here we confirm transmission multipaths reflected off the
environment arriving at a receiver with sufficient delay relative to the direct
signal cause CPDI. We propose a ray-propagation based model to estimate the
arrival of energy via multipaths to predict CPDI occurrence, and we show how
deeper deployments are particularly susceptible. Methods: A series of experiments
were designed to develop and validate our model. Deep (300 m) and shallow (25 m)
ranging experiments were conducted using Vemco V13 acoustic tags and VR2-W
receivers. Probabilistic modeling of hourly detections was used to estimate the
average distance a tag could be detected. A mechanistic model for predicting the
arrival time of multipaths was developed using parameters from these experiments
to calculate the direct and multipath path lengths. This model was retroactively
applied to the previous ranging experiments to validate CPDI observations. Two
additional experiments were designed to validate predictions of CPDI with respect
to combinations of deployment depth and distance. Playback of recorded tags in a
tank environment was used to confirm multipaths arriving after the receiver's
blanking interval cause CPDI effects. Results: Analysis of empirical data
estimated the average maximum detection radius (AMDR), the farthest distance at
which 95% of tag transmissions went undetected by receivers, was between 840 and
846 m for the deep ranging experiment across all factor permutations. From these
results, CPDI was estimated within a 276.5 m radius of the receiver. These
empirical estimations were consistent with mechanistic model predictions. CPDI
affected detection at distances closer than 259-326 m from receivers. AMDR
determined from the shallow ranging experiment was between 278 and 290 m with
CPDI neither predicted nor observed. Results of validation experiments were
consistent with mechanistic model predictions. Finally, we were able to predict
detection/nondetection with 95.7% accuracy using the mechanistic model's
criterion when simulating transmissions with and without multipaths. Discussion:
Close proximity detection interference results from combinations of depth and
distance that produce reflected signals arriving after a receiver's blanking
interval has ended. Deployment scenarios resulting in CPDI can be predicted with
the proposed mechanistic model. For deeper deployments, sea-surface reflections
can produce CPDI conditions, resulting in transmission rejection, regardless of
the reflective properties of the seafloor.
PMID- 29340249
TI - A streptomycin resistance marker in H. parasuis based on site-directed mutations
in rpsL gene to perform unmarked in-frame mutations and to verify natural
transformation.
AB - Haemophilus parasuis is a member of the family Pasteurellaceae and a major
causative agent of Glasser's disease. This bacterium is normally a benign swine
commensal but may become a deadly pathogen upon penetration into multiple
tissues, contributing to severe lesions in swine. We have established a
successive natural transformation-based markerless mutation system in this
species. However, the two-step mutation system requires screening of natural
competent cells, and cannot delete genes which regulate natural competence per
se. In this study, we successfully obtained streptomycin-resistant derivatives
from H. parasuis wild type strain SC1401 by using ethyl methane sulfonate (EMS,
CH3SO2OC2H5). Upon sequencing and site-directed mutations, we uncovered that the
EMS-induced point mutation in rpsL at codon 43rd (AAA -> AGA; K43R) or at 88th
(AAA -> AGA; K88R) confers a much higher streptomycin resistance than clinical
isolates. We have applied the streptomycin resistance marker as a positive
selection marker to perform homologous recombination through conjugation and
successfully generated a double unmarked in-frame targeted mutant
1401D88?tfox?arcA. Combined with a natural transformation-based knockout system
and this genetic technique, multiple deletion mutants or attenuated strains of H.
parasuis can be easily constructed. Moreover, the mutant genetic marker rpsL and
streptomycin resistant phenotypes can serve as an effective tool to select
naturally competent strains, and to verify natural transformation quantitatively.
PMID- 29340250
TI - Integrated genomic analyses of lung squamous cell carcinoma for identification of
a possible competitive endogenous RNA network by means of TCGA datasets.
AB - The etiology of cancer includes aberrant cellular homeostasis where a compromised
RNA regulatory network is a prominent contributing factor. In particular,
noncoding RNAs including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs)
were recently shown to play important roles in the initiation, progression, and
metastasis of human cancers. Nonetheless, a mechanistic understanding of
noncoding RNA functions in lung squamous cell carcinoma (LUSC) is lacking. To
fill this critical gap in knowledge, we obtained mRNA, miRNA, and lncRNA
expression data on patients with LUSC from the updated Cancer Genome Atlas (TCGA)
database (2016). We successfully identified 3,366 mRNAs, 79 miRNAs, and 151
lncRNAs as key contributing factors of a high risk of LUSC. Furthermore, we
hypothesized that the lncRNA-miRNA-mRNA regulatory axis positively correlates
with LUSC and constructed a competitive endogenous RNA (ceRNA) network of LUSC by
targeting interrelations with significantly aberrant expression data between
miRNA and mRNA or lncRNA. Six ceRNAs (PLAU, miR-31-5p, miR-455-3p, FAM83A-AS1,
MIR31HG, and MIR99AHG) significantly correlated with survival (P < 0.05).
Finally, real-time quantitative PCR analysis showed that PLAU is significantly
upregulated in SK-MES-1 cells compared with 16-BBE-T cells. Taken together, our
findings represent new knowledge for a better understanding the ceRNA network in
LUSC biology and pave the way to improved diagnosis and prognosis of LUSC.
PMID- 29340251
TI - The relationships between exercise and affective states: a naturalistic,
longitudinal study of recreational runners.
AB - Background: Although people generally feel more positive and more energetic in
the aftermath of exercise than before, longitudinal research on how exercise
relates to within-person fluctuations in affect over the course of everyday life
is still relatively limited. One constraint on doing such research is the need to
provide participants with accelerometers to objectively record their exercise,
and pagers to capture affective reports. Aims: We aimed to develop a methodology
for studying affect and exercise using only technology that participants already
possess, namely GPS running watches and smartphones. Using this methodology, we
aimed to characterize within-individual fluctuations in affective valence and
arousal in relation to bouts of exercise, and explore possible moderators of
these fluctuations. Methods: We recruited a sample of 38 recreational runners.
Participants provided daily affective reports for six weeks using their
smartphones. Information on their runs was harvested from their own GPS devices
via an online platform for athletes. Results: Average valence and arousal were
higher on days when the person had run than on the next day, and higher the day
after a run than on the days after that. Over the course of the day of a run,
valence and arousal declined significantly as the time since the run increased.
Physically fitter participants had more positive valence overall, and this was
particularly true when they had not run recently. There was some evidence of
higher-dose (i.e., longer and faster) runs being associated with lower arousal on
the next and subsequent days. Gender did not moderate associations between
running and valence or arousal. Discussion: Our study demonstrated the potential
for studying the associations between affect and exercise in a way that is
precise, undemanding for participants, and convenient for researchers, using
technologies that participants already own and use.
PMID- 29340253
TI - RBiomirGS: an all-in-one miRNA gene set analysis solution featuring target mRNA
mapping and expression profile integration.
AB - Background: With the continuous discovery of microRNA's (miRNA) association with
a wide range of biological and cellular processes, expression profile-based
functional characterization of such post-transcriptional regulation is crucial
for revealing its significance behind particular phenotypes. Profound advancement
in bioinformatics has been made to enable in depth investigation of miRNA's role
in regulating cellular and molecular events, resulting in a huge quantity of
software packages covering different aspects of miRNA functional analysis.
Therefore, an all-in-one software solution is in demand for a comprehensive yet
highly efficient workflow. Here we present RBiomirGS, an R package for a miRNA
gene set (GS) analysis. Methods: The package utilizes multiple databases for
target mRNA mapping, estimates miRNA effect on the target mRNAs through miRNA
expression profile and conducts a logistic regression-based GS enrichment.
Additionally, human ortholog Entrez ID conversion functionality is included for
target mRNAs. Results: By incorporating all the core steps into one package,
RBiomirGS eliminates the need for switching between different software packages.
The modular structure of RBiomirGS enables various access points to the analysis,
with which users can choose the most relevant functionalities for their workflow.
Conclusions: With RBiomirGS, users are able to assess the functional significance
of the miRNA expression profile under the corresponding experimental condition by
minimal input and intervention. Accordingly, RBiomirGS encompasses an all-in-one
solution for miRNA GS analysis. RBiomirGS is available on GitHub
(http://github.com/jzhangc/RBiomirGS). More information including instruction and
examples can be found on website (http://kenstoreylab.com/?page_id=2865).
PMID- 29340252
TI - Positive selection on human gamete-recognition genes.
AB - Coevolution of genes that encode interacting proteins expressed on the surfaces
of sperm and eggs can lead to variation in reproductive compatibility between
mates and reproductive isolation between members of different species. Previous
studies in mice and other mammals have focused in particular on evidence for
positive or diversifying selection that shapes the evolution of genes that encode
sperm-binding proteins expressed in the egg coat or zona pellucida (ZP). By
fitting phylogenetic models of codon evolution to data from the 1000 Genomes
Project, we identified candidate sites evolving under diversifying selection in
the human genes ZP3 and ZP2. We also identified one candidate site under positive
selection in C4BPA, which encodes a repetitive protein similar to the mouse
protein ZP3R that is expressed in the sperm head and binds to the ZP at
fertilization. Results from several additional analyses that applied population
genetic models to the same data were consistent with the hypothesis of selection
on those candidate sites leading to coevolution of sperm- and egg-expressed
genes. By contrast, we found no candidate sites under selection in a fourth gene
(ZP1) that encodes an egg coat structural protein not directly involved in sperm
binding. Finally, we found that two of the candidate sites (in C4BPA and ZP2)
were correlated with variation in family size and birth rate among Hutterite
couples, and those two candidate sites were also in linkage disequilibrium in the
same Hutterite study population. All of these lines of evidence are consistent
with predictions from a previously proposed hypothesis of balancing selection on
epistatic interactions between C4BPA and ZP3 at fertilization that lead to the
evolution of co-adapted allele pairs. Such patterns also suggest specific
molecular traits that may be associated with both natural reproductive variation
and clinical infertility.
PMID- 29340254
TI - Response of methane production via propionate oxidation to carboxylated
multiwalled carbon nanotubes in paddy soil enrichments.
AB - Carboxylated multiwalled carbon nanotubes (MWCNTs-COOH) have become a growing
concern in terms of their fate and toxicity in aqueous environments. Methane
(CH4) is a major product of organic matter degradation in waterlogged
environments. In this study, we determined the effect of MWCNTs-COOH on the
production of CH4 from propionate oxidation in paddy soil enrichments. The
results showed that the methanogenesis from propionate degradation was
accelerated in the presence of MWCNTs-COOH. In addition, the rates of CH4
production and propionate degradation increased with increasing concentrations of
MWCNTs-COOH. Scanning electron microscopy (SEM) observations showed that the
cells were intact and maintained their structure in the presence of MWCNTs-COOH.
In addition, SEM and fluorescence in situ hybridization (FISH) images revealed
that the cells were in direct contact with the MWCNTs and formed cell-MWCNTs
aggregates that contained both bacteria and archaea. On the other hand, nontoxic
magnetite nanoparticles (Fe3O4) had similar effects on the CH4 production and
cell integrity as the MWCNTs-COOH. Compared with no nanomaterial addition, the
relative abundances of Geobacter and Methanosarcina species increased in the
presence of MWCNTs-COOH. This study suggests that MWCNTs-COOH exerted positive
rather than cytotoxic effects on the syntrophic oxidation of propionate in paddy
soil enrichments and affected the bacterial and archaeal community structure at
the test concentrations. These findings provide novel insight into the
consequences of nanomaterial release into anoxic natural environments.
PMID- 29340255
TI - Habitat use in south-west European skinks (genus Chalcides).
AB - Background: Congeneric species of reptiles frequently exhibit partitioning in
terms of their use of habitats or trophic resources in order to reduce
competition. In this study, we investigated habitat use by two species of
European skinks: Chalcides bedriagai and Chalcides striatus, based on 49 records
from southern France, Spain, and Portugal. Methods: We measured three levels of
niche descriptors: macroscale (climate, topography, and substrate), mesoscale
(plant associations), and microscale (vegetation cover and shelters). We assessed
the associations between these environmental descriptors and the occurrence of
the skinks. Results: Our results showed that the two species occupied opposite
extremes of the ecological gradient i.e., C. bedriagai in semi-arid environments
and C. striatus in temperate-oceanic environments, but there was broad ecological
overlap in transitional climates at all of the habitat scales examined. This
overlap was demonstrated by the presence of syntopy in geographically distant
sites with different environmental characteristics. Discussion: The morphological
differences between the two species, and possibly their different use of
microhabitats, might favor this mesoscale overlap between congeneric species,
which is relatively unusual in Mediterranean lizards.
PMID- 29340256
TI - Clinical Cholecystitis in the Absence of the Gallbladder.
AB - The congenital absence of the gallbladder (CAG) is a rare condition with an
incidence of 13-65 cases/ 100,000 in the general population. This occurs when the
gallbladder and the cystic duct fail to bud from the common bile duct during the
fifth week of gestation. Most commonly, the patients with congenital absence of
the gallbladder are asymptomatic. When symptomatic, they present as biliary
colic, dyspepsia, jaundice or very rarely as acute cholecystitis. We present a
case of a 27-year-old female who presented with acute right upper quadrant
abdominal pain. Further evaluation with an ultrasound revealed a contracted
gallbladder with stones. The hepatobiliary iminodiacetic acid scan was
significant for non-visualization of the gallbladder, consistent with cystic duct
obstruction. The laparoscopic cholecystectomy was attempted, however, the
gallbladder was not visualized, and the procedure was aborted. The post-operative
magnetic resonant cholangiopancreatography was consistent with the diagnosis of
congenital absence of gallbladder.
PMID- 29340257
TI - Symmetrical Drug-related Intertriginous and Flexural Exanthema Induced by
Doxycycline.
AB - Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a
cutaneous drug reaction characterized by erythema over the buttocks, thighs,
groin, and flexural regions most commonly associated with the use of beta-lactam
antibiotics. Although the exact pathophysiology of this disease remains unknown,
it is theorized to be the result of a delayed hypersensitivity response
presenting as a cutaneous eruption days to weeks after exposure to the drug. The
treatment involves discontinuation of the suspected medication, symptomatic
control of pruritus, and topical steroid therapy. A 51-year-old woman with
homocystinuria and fibromyalgia was admitted with fevers, pancytopenia (later
diagnosed to be acute myelogenous leukemia), and a targetoid cutaneous eruption
in the setting of a recent tick bite. She was subsequently noted to have
symmetric, pruritic, erythematous papules over the lateral neck, retroauricular
regions, lateral aspects of the inframammary regions, medial upper arms, axillae,
and the lower abdomen two weeks after starting doxycycline. Considering the
morphology, distribution, and intense pruritis associated with the eruption, a
diagnosis of SDRIFE was made. Doxycycline discontinuation along with topical
steroid therapy resulted in the resolution of the eruption and pruritus. Given
the widespread use of doxycycline, clinicians should be aware of this possible
side effect.
PMID- 29340258
TI - Atypical Initial Presentation of Painful Muscle Cramps in a Patient with
Amyotrophic Lateral Sclerosis: A Case Report and Brief Review of the Literature.
AB - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized
clinically by progressive muscle weakness that can occur proximally or distally
in either the upper or lower extremities. It includes both upper motor neuron
signs (spasticity, hyperreflexia, clonus, and Babinski sign) and lower motor
neuron signs (atrophy, weakness, and muscle fasciculation). Initial presentation
of progressively painful muscle cramps should lead the physician to screen for
other signs of amyotrophic lateral sclerosis. We report the case of a 51-year-old
male, who presented with dull muscle cramps in the right upper shoulder and arm.
After a careful history and physical exam, it was found that patient had both
upper and lower motor neuron signs; therefore, a diagnosis of amyotrophic lateral
sclerosis was made. Amyotrophic lateral sclerosis should strongly be considered
in the differential diagnosis of patients presenting with an atypical initial
presentation of progressively painful muscle cramps.
PMID- 29340260
TI - Nutritional status is associated with the return home in a long-term care health
facility.
AB - Background: The purpose of this study was to determine the association between
nutritional status and the return home of older people living in a long-term care
health facility (LCHF). Methods: A nested case control study was performed in 116
people >=65 years of age in a single LCHF. Nutritional status was assessed using
the Mini Nutritional Assessment Short Form (MNA-SF) and activities of daily
living by the Functional Independence Measure (FIM). The return home, duration of
rehabilitation, and the family wanting the patient to return home were obtained
from clinical records. Multivariate logistic regression analysis was used to
assess whether malnutrition had independent effects on the return home. Results:
The participants included 36 males and 80 females with a mean age of 82 years.
Thirty-seven people returned home while 79 did not. The MNA-SF showed that 80
subjects were malnourished. Sixty-six of the participants received rehabilitation
for longer than 1 hour per week, while 50 received rehabilitation for <1 hour.
The proportion of subjects with malnutrition who returned home was significantly
lower (P = .003) than in participants who did not return home. Multivariate
logistic regression analysis showed that malnutrition (adjusted odds ratio [AOR],
0.23; 95% confidence interval [CI], 0.08-0.65; P = .006), total FIM score (AOR,
1.03; 95% CI, 1.01-1.06; P = .012), and the family wanting the patient to return
home (AOR, 9.46; 95% CI, 3.19-28.12; P < .001) were independently associated with
the return home. Conclusions: Nutritional status is associated with the return
home in older people living in LCHF.
PMID- 29340259
TI - Relationships between road-distance to primary care facilities and ischemic heart
disease and stroke mortality in Hokkaido, Japan: A Bayesian hierarchical approach
to ecological count data.
AB - Objective: Poor access to a primary care physician may lead to poor control of
risk factors for disease. This study investigated whether geographic access to a
primary care physician was related to ischemic heart disease and stroke
mortality. Methods: Road-distances from the centroids of the basic unit blocks of
the 2010 Japanese Census to the nearest primary care facilities in Hokkaido,
northern Japan, were measured using geographic information system (GIS) software.
Next, block population-weighted mean road-distances to primary care facilities in
all municipalities were calculated. The numbers of deaths from ischemic heart
disease and stroke were obtained from the Vital Statistics Bureau. A Bayesian
spatial conditional autoregressive (CAR) model was used to analyze relative risk
(RR) by road-distance with the numbers of physicians in the municipality included
as a covariate. Results: Relative risk (per 1 kilometer increased) of death from
ischemic heart disease to road-distance to the nearest primary care facility was
not significantly higher in men (1.108: 95% credible interval [CI] 0.999-1.037)
and women (1.023: 95% CI 1.000-1.046). However, RR of death from stroke was
significantly higher in men (1.019: 95% CI 1.005-1.032) and women (1.019: 95% CI
1.006-1.033). Conclusion: Longer road-distance to a primary care facility may
increase the risk of stroke mortality.
PMID- 29340261
TI - Medical support with acupuncture and massage therapies for disaster victims.
AB - Background: After the Great East Japan Earthquake and Tsunami Disaster (GEJED)
and Joso City Flood (JCF), a number of people were relocated to evacuation
centers. In situations following a large-scale disaster, acupuncture can be
applied for various health problems in evacuation centers. In this study, we
report the medical support operation for evacuees with acupuncture and massage
therapy (AP/MT) and its effectiveness. In addition, we propose an experience
based guideline for AP/MT in such situations. Methods: We retrospectively
investigated the treatment with AP/MT after GEJED and JCF based on the medical
records that were coded. We performed AP/MT for evacuees or supporters in Iwanuma
City, Shiogama City, and Natori City after the GEJED (total number of 1042), and
in Joso City after the JCF (total number of 110). Results: The most common
complaints, shoulder, back, and knee pain, were reported in 67.6% of patients
after the GEJED and 80.9% of patients after the JCF. Acupuncture and massage
therapy (AP/MT) significantly decreased the median Face Scale score of subjective
symptoms in evacuees (before, 3.0 vs after, 1.0, P < .001) and supporters
(before, 3.0 vs after, 1.0, P < .001) in the JCF. Conclusions: Evacuees and
supporters in affected areas could benefit from AP/MT for relief of subjective
symptoms. For proper management and safety support, we proposed a guideline of
AP/MT for postdisaster situations.
PMID- 29340262
TI - Recovery from a depressive episode during postgraduate residency training is
associated with senior doctors' support.
AB - Background: Depression among doctors in residency training can have significant
impacts on the health of the residents and on patient safety. This study aimed to
investigate factors associated with recovery from a depressive episode
experienced during postgraduate residency training. Methods: A questionnaire was
administered to 2935 first-year residents at the beginning of residency training
in 2011; follow-up surveys were conducted after 3 months and at the end of the
training in 2013. The questionnaire included the Center for Epidemiologic Studies
Depression Scale and the Senior Doctor's Support Scale (SDSS). Logistic
regression was used to identify associations between factors that may have been
related to recovery from depressive episodes. Results: A total 182 residents
experienced a depressive episode in the 3 months after starting residency
training. When reassessed at the end of the 2-year training, 102 (56%) residents
had recovered from the episode and 80 (44%) had not. Increased odds of recovery
were associated with a middle or high score on the SDSS (middle score odds ratios
[OR] 4.45, 95% confidence interval [CI] 1.0-18.0, P = .04; and high score OR
5.70, 95% CI 1.4-23.4, P = .02). Conclusions: Support from senior doctors should
be enhanced to optimize recovery from depressive episodes experienced after the
start of residency training.
PMID- 29340263
TI - Diagnostic delay for imported malaria: A case of Plasmodium falciparum malaria
misdiagnosed as common cold.
AB - A 37-year-old Japanese man experienced fever and headache 8 days after returning
to Japan following a 6-month stay in Nigeria. He visited two clinics but was sent
home from each with a diagnosis of common cold. He was eventually brought to the
emergency department with an altered mental status. Severe P. falciparum malaria
was confirmed; his initial parasitemia index was 5.4%. He recovered fully with
antimalarial treatment. This case suggests that primary care physicians should
obtain recent travel history and consider malaria for any febrile patient who has
returned from a malaria-endemic area.
PMID- 29340264
TI - Reactive nonsexually related acute genital ulcers.
AB - The case of a 19-year-old Japanese woman with reactive nonsexually related acute
genital ulcers.
PMID- 29340265
TI - Acute generalized pustular bacterid.
AB - The case of a 70-year-old Japanese man with acute generalized pustular bacterid.
PMID- 29340266
TI - 18F-FDG PET-CT in a patient with methotrexate-associated lymphoproliferative
disorder.
AB - 18F-FDG PET-CT clearly demonstrated the disease activity of MTX-LPD.
PMID- 29340267
TI - Postherpetic abdominal pseudohernia: A diagnostic pitfall.
AB - The accurate diagnosis of postherpetic abdominal pseudohernia, the rare
complication of herpes zoster, is essential to avoid unnecessary imaging studies
or surgery. Close observation and waiting for complete recovery are warranted
considering the disease's self-resolving nature and favorable prognosis.
PMID- 29340268
TI - Out with the old, in with the new: Assessing change in screen time when
measurement changes over time.
AB - We examined if screen time can be assessed over time when the measurement
protocol has changed to reflect advances in technology. Beginning in 2011, 929
youth (9-12 years at time one) living in in New Brunswick (Canada) self-reported
the amount of time spent watching television (cycles 1-13), using computers
(cycles 1-13), and playing video games (cycles 3-13). Using longitudinal
invariance to test a shifting indicators model of screen time, we found that the
relationships between the latent variable reflecting overall screen time and the
indicators used to assess screen time were invariant across cycles (weak
invariance). We also found that 31 out of 37 indicator intercepts were invariant,
meaning that most indicators were answered similarly (i.e., on the same metric)
across cycles (partial strong invariance), and that 28 out of 37 indicator
residuals were invariant indicating that similar sources of error were present
over time (partial strict invariance). Overall, across all survey cycles, 76% of
indicators were fully invariant. Whereas issues were noted when new examples of
screen-based technology (e.g., iPads) were added, having established partial
invariance, we suggest it is still possible to assess change in screen time
despite having changing indicators over time. Although it is not possible to draw
definitive conclusions concerning other self-report measures of screen time, our
findings may assist other researchers considering modifying self-report measures
in longitudinal studies to reflect technological advancements and increase the
precision of their results.
PMID- 29340269
TI - Examining relationships between perceptions and objective assessments of
neighborhood environment and sedentary time: Data from the Washington, D.C.
Cardiovascular Health and Needs Assessment.
AB - Sedentary time (ST) and neighborhood environment (NE) are predictors of
cardiovascular (CV) health. However, little is known about ST's relationship with
NE. We examined associations of perceived and objective NE with ST in the
predominantly African American faith-based population of the Washington, D.C. CV
Health and Needs Assessment. After using community-based research principles,
participants reported NE perceptions, including sidewalks, recreational areas,
and crime presence. Factor analysis was conducted to explore pertinent
constructs; factor sums were created and combined as Total Perception Score (TPS)
(higher score = more favorable perception). Objective NE was assessed using
Google Maps and the Active Neighborhood Checklist (ANC). ST was self-reported.
Linear regression determined relationships between TPS and ST, and ANC scores and
ST, for 1) overall population, 2) lower median-income D.C. areas, and 3) higher
median-income DC and Maryland areas. For the sample (N = 98.9% African-American,
78% female), lower median-income areas had significantly lower mean TPS and ANC
scores than higher median-income areas (p < 0.001). Three factors (neighborhood
violence, physical/social environment, and social cohesion) were associated with
overall NE perception. Among those in lower median-income areas, there was a
negative association between TPS and ST that remained after covariate adjustment;
this was not observed in higher median-income areas. There was no association
between ANC scores and ST. Poorer NE perception is associated with greater ST for
those in lower income areas, while objective environment is not related to ST.
Multi-level interventions are needed to improve NE perceptions in lower-median
income areas, reduce ST, and improve CV health.
PMID- 29340270
TI - Outpatient, combined use of opioid and benzodiazepine medications in the United
States, 1993-2014.
AB - The combined use of opioid and benzodiazepine medications increases the risk of
hazardous effects, such as respiratory depression. Although recent increases in
outpatient use of opioid prescriptions have been documented, there are limited
data regarding rates and correlates of combined opioid and benzodiazepines among
adults in outpatient settings. Our objective was to examine annual trends in
outpatient visits including opioids, benzodiazepines, and their combination among
adults as well as clinical and demographic correlates. We used data from the 1993
2014 National Ambulatory Medical Care Survey (NAMCS) among non-elderly (i.e.,
ages 18-64 years) adults to examine the probability of a visit including an
opioid, benzodiazepine, or their combination, in addition to clinical and
demographic correlates. From 1993 to 2014, benzodiazepines-with-opioids visits
increased from 9.8 to 62.5 (OR = 9.23, 95% CI = 5.45-15.65) per 10,000 visits.
Highest-represented groups among benzodiazepines-with-opioids visits were older
(50-64 years) (49.1%), white (88.8%), commercially insured (58.0%) patients
during their first visit (87.6%) to a primary-care physician (41.9%). We
identified a significant increase in the outpatient co-prescription of opioids
and benzodiazepines, notably among adults aged 50-64 years during primary-care
visits. Educational and policy changes to provide alternatives to benzodiazepine
with-opioid co-prescription and limiting opioid prescription to pain specialists
may reduce rates of this potentially hazardous combination.
PMID- 29340271
TI - Transit use and physical activity: Findings from the Houston travel-related
activity in neighborhoods (TRAIN) study.
AB - Transportation-related physical activity can significantly increase daily total
physical activity through active transportation or walking/biking to transit
stops. The purpose of this study was to assess the relations between transit-use
and self-reported and monitor-based physical activity levels in a predominantly
minority population from the Houston Travel-Related Activity in Neighborhoods
(TRAIN) Study. This was a cross-sectional analysis of 865 adults living in
Houston, Texas between 2013 and 2015. The exposure variable was transit-use (non
users, occasional users, and primary users). Self-reported and accelerometer
determined physical activity were the outcomes of interest. Regression models
adjusting for age, sex, race/ethnicity, and other covariates of interest were
built to test the hypothesis that transit user status was directly associated
with 1) minutes of moderate-intensity physical activity and 2) the prevalence of
achieving the physical activity guidelines. The majority of participants were
female, non-Hispanic black, and almost one-third had a high school education or
less. After adjustment, primary transit-use was associated with 134.2 (p < 0.01)
additional mean minutes per week of self-reported moderate-intensity
transportation-related physical activity compared to non-users. Further, primary
users had 7.3 (95% CI: 2.6-20.1) times the relative adjusted odds of meeting
physical activity recommendations than non-users based on self-reported
transportation-related physical activity. There were no statistically significant
associations of transit-use with self-reported leisure-time or accelerometer
derived physical activity. Transit-use has the potential for a large public
health impact due to its sustainability and scalability. Therefore, encouraging
the use of transit as a means to promote physical activity should be examined in
future studies.
PMID- 29340272
TI - Migraine-preventive prescription patterns by physician specialty in ambulatory
care settings in the United States.
AB - Many adults with migraine who require preventive therapy are often not prescribed
the proper medications. The most likely reason is that primary care physicians
are unacquainted with preventive medications for migraine. The present study
assessed the migraine-preventive prescription patterns in office visits using
data from the National Ambulatory Medical Care Survey from 2006 to 2009 in the
United States. Patients who were 18 years or older and diagnosed with migraine
were included in the analysis. In accordance with the recommendations of the
headache guidelines, we included beta-blockers, antidepressants, triptans for
short-term prevention of menstrual migraine, and other triptans for acute
treatment. Weighted visits of adults with migraine prescribed with preventive
medication ranged from 32.8% in 2006 to 38.6% in 2009. Visits to primary care
physicians accounted for 72.6% of the analyzed adult migraine visits.
Anticonvulsants (odds ratio [OR] 0.29, 95% confidence interval [CI] 0.14-0.57, p
< 0.001) and triptans for menstrual migraine (OR 0.50, 95% CI 0.28-0.91, p =
0.025) were less frequently prescribed by primary care physicians compared with
specialty care physicians, such as neurologists and psychiatrists. There were no
significant differences in the prescription patterns of antidepressants and beta
blockers between primary and specialty care physicians. Beta-blockers were
prescribed to patients with comorbidity of hypertension, and antidepressants were
used by patients with comorbidity of depression. There are differences in the
prescription patterns of certain type of preventive medications between primary
care physicians and specialty care physicians.
PMID- 29340273
TI - Effects of Portal Vein Thrombosis on the Outcomes of Liver Cirrhosis: A Mexican
Perspective.
PMID- 29340274
TI - Breaking through Restricting Bottleneck for Better Asthma Control.
PMID- 29340276
TI - Clinical Value of Ultrasonography in Diagnosis of Pulmonary Embolism in
Critically Ill Patients.
AB - Pulmonary embolism (PE) is a clinical emergency that will increase the mortality
if complicated with unstable hemodynamics. Because of its nonspecific clinical
symptoms, it's a great challenge to make a PE diagnosis. The golden standard to
diagnose PE is computed tomography of pulmonary artery (CTPA), but a diagnosis of
PE also composed of evaluation of PE risk factors, possibilities, and risk
stratification. Ultrasonography may detect right ventricle strain related to
hemodynamic change, intravascular thrombosis, thrombosis in right heart or
pulmonary arteries, pulmonary infarction, and local pleural effusion. Combination
of ultrasound and traditional PE possibility evaluation score may further improve
the pretest probability of CTPA. A comprehensive ultrasonography may sometimes
rule out PE and may disclose other causes for the clinical situations. A heart
lung-vessel-integrated multiorgan ultrasonography can help with the diagnosis of
PE and so should be a necessary weapon for the physicians.
PMID- 29340275
TI - Timing of Transjugular Intrahepatic Portosystemic Shunt for Budd-Chiari Syndrome:
An Italian Hepatologist's Perspective.
AB - Budd-Chiari syndrome (BCS) management flow-chart is derived from experts' opinion
and is not evidence-based. Guidelines suggest BCS management should follow a
stepwise strategy: medical therapy as first-line treatment, revascularization or
transjugular intrahepatic portosystemic shunt (TIPS) if no response to medical
therapy, and liver transplant as rescue therapy. Recent evidence suggests that
only medical therapy results in a bad long-term outcome. The biggest criticism of
guidelines is the indication that BCS should receive further treatment only when
hemodynamic consequences of portal hypertension become clinically evident. Recent
data support that in BCS liver fibrosis could arise from chronic microvascular
ischemia. A reasoning model of BCS physiopathology is that impaired hepatic vein
outflow has hemodynamic consequences on portal hypertension development and
causes hepatic fibrosis and liver failure through chronic ischemic damage. On
this assumption is the concept that relieving liver congestion could ameliorate
liver function and prevent development of BCS complications. Recently, early
interventional treatment with TIPS for BCS has been reported to be effective.
Early TIPS seems to be the best option for BCS management. Future multicenter
controlled studies should compare the outcome of BCS treated with early
interventional treatment compared with stepwise strategy.
PMID- 29340277
TI - Comparative Computed Flow Dynamic Analysis of Different Optimization Techniques
in Left Main Either Provisional or Culotte Stenting.
AB - Background and Objectives: Provisional and culotte are the most commonly used
techniques in left main (LM) stenting. The impact of different post-dilation
techniques on fluid dynamic of LM bifurcation has not been yet investigated. The
aim of this study is to evaluate, by means of computational fluid dynamic
analysis (CFD), the impact of different post-dilation techniques including
proximal optimization technique (POT), kissing balloon (KB), POT-Side-POT and POT
KB-POT, 2-steps Kissing (2SK) and Snuggle Kissing balloon (SKB) on flow dynamic
profile after LM provisional or culotte stenting. Methods: We considered an LM
LCA-LCX bifurcation reconstructed after reviewing 100 consecutive patients (mean
age 71.4 +/- 9.3 years, 49 males) with LM distal disease. The diameters of LAD
and LCX were modelled according to the Finnet's law as following: LM 4.5 mm, LAD
3.5 mm, LCX 2.75 mm, with bifurcation angle set up at 55 degrees . Xience third
generation stent (Abbot Inc., USA) was reconstructed and virtually implanted in
provisional/cross-over and culotte fashion. POT, KB, POT-side-POT, POT-KB-POT,
2SK and SKB were virtually applied and analyzed in terms of the wall shear stress
(WSS). Results: Analyzing the provisional stenting, the 2SK and KB techniques had
a statistically significant lower impact on the WSS at the carina, while POT
seemed to obtain a neutral effect. In the wall opposite to the carina, the more
physiological profile has been obtained by KB and POT with higher WSS value and
smaller surface area of the lower WSS. In culotte stenting, at the carina, POT-KB
POT and 2SK had a very physiological profile; while at the wall opposite to the
carina, 2SK and POT-KB-POT decreased significantly the surface area of the lower
WSS compared to the other techniques. Conclusion: From the fluid dynamic point of
view in LM provisional stenting, POT, 2SK and KB showed a similar beneficial
impact on the bifurcation rheology, while in LM culotte stenting, POT-KB-POT and
2SK performed slightly better than the other techniques, probably reflecting a
better strut apposition.
PMID- 29340278
TI - Endoscopic Ultrasound-guided Pancreatic Pseudocyst Drainage with Lumen-apposing
Metal Stents or Plastic Double-pigtail Stents: A Multifactorial Analysis.
AB - Objective: To compare the efficiency of plastic and metal stents for symptomatic
pancreatic pseudocyst (PP) drainage and analyze other main associated factors
that affect the outcome of drainage therapy. Method: Rates of technical and
clinical success, procedure-related side effects (hemorrhage, stent migration,
and cyst rupture), reinterventions, and duration of hospital stay. Results: There
were 52 patients, 40 patients underwent plastic stent placement and 12 patients
underwent lumen-apposing metal stent (LAMS) placement. The total rate of
technical success was 100%. The total rate of clinical success was 100%. The
total rate of adverse events was 7.7% (4/52). On multiple logistic regression
analysis, the use of plastic stents (P < 0.05, Exp B = 12.168) and the presence
of a large cyst (P < 0.05, Exp B = 1.036) were shown to significantly increase
the risk of reintervention. On multivariate linear regression analysis, etiology
of pseudocyst (P < 0.05, B = -8.427, -9.785, -5.514) was associated with
prolonged hospital stent, while stent type was not shown be a factor (P > 0.05).
Conclusion: Both plastic and LAMSs are proven to be highly efficient in PP
drainage. The LAMS is superior in preventing complications such as migration and
cyst leakage and reducing the rate of reintervention.
PMID- 29340279
TI - Effect of MTHFR A1298C and MTRR A66G Genetic Mutations on Homocysteine Levels in
the Chinese Population: A Systematic Review and Meta-analysis.
AB - Background and Objectives: The Chinese population typically has inadequate folate
intake and no mandatory folic acid fortification. Methylenetetrahydrofolate
reductase (MTHFR) and methionine synthase reductase (MTRR) are the two key
regulatory enzymes in the folate/homocysteine (Hcy) metabolism. Hcy has been
implicated in the pathogenesis of cardiovascular disease. We conducted a meta
analysis to assess whether the MTHFR gene A1298C and the MTRR gene A66G
polymorphisms affect Hcy levels in the Chinese population. Methods: This analysis
included 13 studies with Hcy levels reported as one of the study measurements.
Summary estimates of weighted mean differences and 95% confidence intervals (CIs)
were obtained using random-effect models. Results: Overall, there were no
significant differences in Hcy concentrations between participants with the MTHFR
1298 CC (12 trials, n = 129), AA (n = 2166; beta, -0.51 MUmol/L; 95%CI: -2.14,
1.11; P = 0.53), or AC genotype (n = 958; beta, 0.55 MUmol/L; 95%CI: -0.72, 1.82;
P = 0.40). Consistently, compared to those with the MTRR 66 GG genotype (6
trials, n = 156), similar Hcy concentrations were found in participants with the
AA (n = 832; beta, -0.43 MUmol/L; 95%CI: -1.04, 0.17; P = 0.16) or AG (n =743;
beta, -0.57 MUmol/L; 95%CI: -1.46, 0.31; P = 0.21) genotype. Similar results were
observed for the dominant and recessive models. Conclusions: Neither the MTHFR
A1298C polymorphism nor the MTRR A66G polymorphism affects Hcy levels in the
Chinese population.
PMID- 29340280
TI - Serum Vitamin D Levels in Treatment-naive Chronic Hepatitis B Patients.
AB - Background and Objectives: According to the demographic health survey conducted
in 2015, Egypt had 10% documented prevalence of anti-HBc positive patients aged 1
59 and 1% viremic patients amongst the population in the same age group, with a
domination of genotype D. Several studies claimed the possible role of vitamin D
deficiency in hepatitis B virus (HBV) replication and disease progression.
Patients and Methods: Serum vitamin D levels [25(OH D3] were assessed in 96 HBeAg
negative non-cirrhotic chronic HBV patients and 25 healthy subjects classified as
following: Group I: 48 chronic HBV patients with persistently normal ALT levels
and HBV DNA level < 2000 IU/mL for >= 6 months; Group II: 48 chronic HBV patients
with CHB with persistently elevated ALT and HBV DNA level >= 2000 IU/mL for >= 6
months; and Group III: 25 apparently healthy subjects with normal liver enzymes
and negative hepatitis viral markers were taken as the control group. Results:
Vitamin D was much more deficient in group II than in group I and group III being
11.55 +/- 3.97 ng/mL, 15.03 +/- 3.45, 27.00 +/- 6.76 ng/mL (P < 0.001),
respectively, and a strong negative correlation was observed between vitamin D
levels and HBV DNA levels (P = 0.043) in groups I and II. Conclusion: The current
study showed high HBV DNA replication in patients with vitamin D deficiency
suggesting the antimicrobial immunomodulatory role of vitamin D.
PMID- 29340281
TI - Urgent Need to Define Pretreatment Predictors of Immune Check Point Inhibitors
Related Endocrinopathies: A Case Report and Review of Literature.
AB - Immune check point inhibitors have revolutionized the treatment of metastatic
malignancies. They are a promising area in oncology and more drugs are likely to
be available in the coming years. Along with the promise of better response
oncologically, there is an increased incidence of endocrinopathies related to
autoimmunity. This case report illustrates the dramatic development of
hypothyroidism in a patient with underlying subclinical hyperthyroidism. It also
suggests the potential pretreatment predictors of endocrinopathies related to
these immune check point inhibitors.
PMID- 29340282
TI - Should Vasoconstrictors be Considered in a Cirrhotic Patient with Acute Non
variceal Upper Gastrointestinal Bleeding?
AB - Varices manifest as a major etiology of upper gastrointestinal bleeding in
patients with chronic liver diseases, such as liver cirrhosis and hepatocellular
carcinoma. By contrast, non-variceal upper gastrointestinal bleeding is rare.
Pharmacological treatment differs between patients with variceal and non-variceal
bleeding. Vasoconstrictors are recommended for the treatment of variceal
bleeding, rather than non-variceal bleeding. In contrast, pump proton inhibitors
are recommended for the treatment of non-variceal bleeding, rather than variceal
bleeding. Herein, we present a case with liver cirrhosis and acute upper
gastrointestinal bleeding who had a high risk of rebleeding (i.e., Child-Pugh
class C, hepatocellular carcinoma, portal vein thrombosis, low albumin, and high
international normalized ratio and D-dimer). As the source of bleeding was
obscure, only terlipressin without pump proton inhibitors was initially
administered. Acute bleeding episode was effectively controlled. After that, an
elective endoscopic examination confirmed that the source of bleeding was
attributed to peptic ulcer, rather than varices. Based on this preliminary case
report, we further discussed the potential role of vasoconstrictors in a patient
with cirrhosis with acute non-variceal upper gastrointestinal bleeding.
PMID- 29340283
TI - European Respiratory Society International Congress 2017: highlights from the
Clinical Assembly.
AB - This article contains highlights and a selection of the scientific advances from
the European Respiratory Society's Clinical Assembly (Assembly 1 and its six
respective groups) that were presented at the 2017 European Respiratory Society
International Congress in Milan, Italy. The most relevant topics from each of the
groups will be discussed, covering a wide range of areas including clinical
problems, rehabilitation and chronic care, thoracic imaging, interventional
pulmonology, diffuse and parenchymal lung diseases, and general practice and
primary care. In this comprehensive review, the newest research and actual data
as well as award-winning abstracts and highlight sessions will be discussed.
PMID- 29340284
TI - Optical imaging during toddlerhood: brain responses during naturalistic social
interactions.
AB - Despite the importance of our ability to interact and communicate with others,
the early development of the social brain network remains poorly understood. We
examined brain activity in 12- to 14-month-old infants while they were
interacting live with an adult in two different naturalistic social scenarios
(i.e., reading a picture book versus singing nursery rhymes with gestures), as
compared to baseline (i.e., showing infants a toy without eye contact or speech).
We used functional near-infrared spectroscopy (fNIRS) recorded over the right
temporal lobe of infants to assess the role of the superior temporal sulcus
temporoparietal junction (STS-TPJ) region during naturalistic social
interactions. We observed increased cortical activation in the STS-TPJ region to
live social stimuli in both socially engaging conditions compared to baseline
during real life interaction, with greater activation evident for the joint
attention (reading book) condition relative to the social nursery rhymes. These
results supported the view that the STS-TPJ region, engaged in the cortical
social brain network, is already specialized in infants for processing social
signals and is sensitive to communicative situations. This study also highlighted
the potential of fNIRS for studying brain function in infants entering
toddlerhood during live social interaction.
PMID- 29340285
TI - Quantitative bone scan lesion area as an early surrogate outcome measure
indicative of overall survival in metastatic prostate cancer.
AB - A clinical validation of the bone scan lesion area (BSLA) as a quantitative
imaging biomarker was performed in metastatic castration-resistant prostate
cancer (mCRPC). BSLA was computed from whole-body bone scintigraphy at baseline
and week 12 posttreatment in a cohort of 198 mCRPC subjects (127 treated and 71
placebo) from a clinical trial involving a different drug from the initial
biomarker development. BSLA computation involved automated image normalization,
lesion segmentation, and summation of the total area of segmented lesions on bone
scan AP and PA views as a measure of tumor burden. As a predictive biomarker,
treated subjects with baseline BSLA [Formula: see text] had longer survival than
those with higher BSLA ([Formula: see text] and [Formula: see text]). As a
surrogate outcome biomarker, subjects were categorized as progressive disease
(PD) if the BSLA increased by a prespecified 30% or more from baseline to week 12
and non-PD otherwise. Overall survival rates between PD and non-PD groups were
statistically different ([Formula: see text] and [Formula: see text]). Subjects
without PD at week 12 had longer survival than subjects with PD: median 398 days
versus 280 days. BSLA has now been demonstrated to be an early surrogate outcome
for overall survival in different prostate cancer drug treatments.
PMID- 29340286
TI - Cancer imaging phenomics toolkit: quantitative imaging analytics for precision
diagnostics and predictive modeling of clinical outcome.
AB - The growth of multiparametric imaging protocols has paved the way for
quantitative imaging phenotypes that predict treatment response and clinical
outcome, reflect underlying cancer molecular characteristics and spatiotemporal
heterogeneity, and can guide personalized treatment planning. This growth has
underlined the need for efficient quantitative analytics to derive high
dimensional imaging signatures of diagnostic and predictive value in this
emerging era of integrated precision diagnostics. This paper presents cancer
imaging phenomics toolkit (CaPTk), a new and dynamically growing software
platform for analysis of radiographic images of cancer, currently focusing on
brain, breast, and lung cancer. CaPTk leverages the value of quantitative imaging
analytics along with machine learning to derive phenotypic imaging signatures,
based on two-level functionality. First, image analysis algorithms are used to
extract comprehensive panels of diverse and complementary features, such as
multiparametric intensity histogram distributions, texture, shape, kinetics,
connectomics, and spatial patterns. At the second level, these quantitative
imaging signatures are fed into multivariate machine learning models to produce
diagnostic, prognostic, and predictive biomarkers. Results from clinical studies
in three areas are shown: (i) computational neuro-oncology of brain gliomas for
precision diagnostics, prediction of outcome, and treatment planning; (ii)
prediction of treatment response for breast and lung cancer, and (iii) risk
assessment for breast cancer.
PMID- 29340287
TI - Fully automated detection of breast cancer in screening MRI using convolutional
neural networks.
AB - Current computer-aided detection (CADe) systems for contrast-enhanced breast MRI
rely on both spatial information obtained from the early-phase and temporal
information obtained from the late-phase of the contrast enhancement. However,
late-phase information might not be available in a screening setting, such as in
abbreviated MRI protocols, where acquisition is limited to early-phase scans. We
used deep learning to develop a CADe system that exploits the spatial information
obtained from the early-phase scans. This system uses three-dimensional (3-D)
morphological information in the candidate locations and the symmetry information
arising from the enhancement differences of the two breasts. We compared the
proposed system to a previously developed system, which uses the full dynamic
breast MRI protocol. For training and testing, we used 385 MRI scans, containing
161 malignant lesions. Performance was measured by averaging the sensitivity
values between 1/8-eight false positives. In our experiments, the proposed system
obtained a significantly ([Formula: see text]) higher average sensitivity
([Formula: see text]) compared with that of the previous CADe system ([Formula:
see text]). In conclusion, we developed a CADe system that is able to exploit the
spatial information obtained from the early-phase scans and can be used in
screening programs where abbreviated MRI protocols are used.
PMID- 29340288
TI - 7T MRI subthalamic nucleus atlas for use with 3T MRI.
AB - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces motor
symptoms in most patients with Parkinson disease (PD), yet may produce untoward
effects. Investigation of DBS effects requires accurate localization of the STN,
which can be difficult to identify on magnetic resonance images collected with
clinically available 3T scanners. The goal of this study is to develop a high
quality STN atlas that can be applied to standard 3T images. We created a high
definition STN atlas derived from seven older participants imaged at 7T. This
atlas was nonlinearly registered to a standard template representing 56 patients
with PD imaged at 3T. This process required development of methodology for
nonlinear multimodal image registration. We demonstrate mm-scale STN localization
accuracy by comparison of our 3T atlas with a publicly available 7T atlas. We
also demonstrate less agreement with an earlier histological atlas. STN
localization error in the 56 patients imaged at 3T was less than 1 mm on average.
Our methodology enables accurate STN localization in individuals imaged at 3T.
The STN atlas and underlying 3T average template in MNI space are freely
available to the research community. The image registration methodology developed
in the course of this work may be generally applicable to other datasets.
PMID- 29340289
TI - Automatic segmentation method of pelvic floor levator hiatus in ultrasound using
a self-normalizing neural network.
AB - Segmentation of the levator hiatus in ultrasound allows the extraction of
biometrics, which are of importance for pelvic floor disorder assessment. We
present a fully automatic method using a convolutional neural network (CNN) to
outline the levator hiatus in a two-dimensional image extracted from a three
dimensional ultrasound volume. In particular, our method uses a recently
developed scaled exponential linear unit (SELU) as a nonlinear self-normalizing
activation function, which for the first time has been applied in medical imaging
with CNN. SELU has important advantages such as being parameter-free and mini
batch independent, which may help to overcome memory constraints during training.
A dataset with 91 images from 35 patients during Valsalva, contraction, and rest,
all labeled by three operators, is used for training and evaluation in a leave
one-patient-out cross validation. Results show a median Dice similarity
coefficient of 0.90 with an interquartile range of 0.08, with equivalent
performance to the three operators (with a Williams' index of 1.03), and
outperforming a U-Net architecture without the need for batch normalization. We
conclude that the proposed fully automatic method achieved equivalent accuracy in
segmenting the pelvic floor levator hiatus compared to a previous semiautomatic
approach.
PMID- 29340290
TI - Tailoring four-dimensional cone-beam CT acquisition settings for fiducial marker
based image guidance in radiation therapy.
AB - Use of four-dimensional cone-beam CT (4D-CBCT) and fiducial markers for image
guidance during radiation therapy (RT) of mobile tumors is challenging due to the
trade-off among image quality, imaging dose, and scanning time. This study aimed
to investigate different 4D-CBCT acquisition settings for good visibility of
fiducial markers in 4D-CBCT. Using these 4D-CBCTs, the feasibility of marker
based 4D registration for RT setup verification and manual respiration-induced
motion quantification was investigated. For this, we applied a dynamic phantom
with three different breathing motion amplitudes and included two patients with
implanted markers. Irrespective of the motion amplitude, for a medium field of
view (FOV), marker visibility was improved by reducing the imaging dose per
projection and increasing the number of projection images; however, the scanning
time was 4 to 8 min. For a small FOV, the total imaging dose and the scanning
time were reduced (62.5% of the dose using a medium FOV, 2.5 min) without losing
marker visibility. However, the body contour could be missing for a small FOV,
which is not preferred in RT. The marker-based 4D setup verification was feasible
for both the phantom and patient data. Moreover, manual marker motion
quantification can achieve a high accuracy with a mean error of [Formula: see
text].
PMID- 29340291
TI - Erratum: Endoscopic esophagogastric anastomosis with luminal apposition Axios
stent (LAS) approach: a new concept for hybrid "Lewis Santy".
AB - [This corrects the article DOI: 10.1055/s-0043-106577.].
PMID- 29340293
TI - Can sedation using a combination of propofol and dexmedetomidine enhance the
satisfaction of the endoscopist in endoscopic submucosal dissection?
AB - Background and study aims: The aim of this pilot randomized controlled trial was
to evaluate and compare the satisfaction of the endoscopist along with the
effectiveness and safety of sedation between sedation protocol using a
combination of propofol (PF) and dexmedetomidine (DEX) (Combination group) and
sedation protocol using PF alone (PF group) during gastric endoscopic submucosal
dissection (ESD). Patients and methods : Fifty-eight patients with gastric
neoplasias scheduled for gastric ESD were enrolled and randomly assigned to the
two groups. The satisfaction scores of the endoscopists and the parameters for
the effectiveness and safety of sedation were evaluated by comparisons between
the two groups. Results : The satisfaction scores of the endoscopists, which were
measured using a visual analogue scale, were significantly higher in the
Combination group than in the PF group (88 vs. 69, P = 0.003). The maintenance
dose of PF was lower in the Combination group than in the PF group (2 mg/kg/h vs.
5 mg/kg/h, P < 0.001), and the number of rescue PF injections was fewer in the
Combination group than in the PF group (2 times vs. 6 times, P < 0.001). The
incidence of bradycardia (defined as a pulse rate <= 45 bpm) in the Combination
group was higher than that in the PF group (37.9 % vs. 10.3 %, P = 0.029).
Conclusions : This study suggests that gastroenterologist-directed sedation using
a combination of PF and DEX during gastric ESD can enhance the satisfaction
levels of endoscopists by providing stable sedation with an acceptable safety
profile.
PMID- 29340294
TI - A comparison of endoscopic and non-endoscopic biliary intervention outcomes in
patients with prior bariatric surgery.
AB - Background and study aims : Endoscopic biliary intervention (BI) is often
difficult to perform in patients with prior bariatric surgery (BRS). We sought to
analyze outcomes of patients with prior BRS undergoing endoscopic and non
endoscopic BI. Patients and methods: The Nationwide Inpatient Sample (2007 -
2011) was reviewed to identify all adult inpatients (>= 18 years) with a history
of BRS undergoing BI. The clinical outcomes of interest were in-patient
mortality, length of stay (LOS), and total hospital charges. Results: There were
7,343 patients with prior BRS who underwent BIs where a majority were endoscopic
(4,482 vs. 2,861, P < 0.01). The mean age was 50+/-30.8 years and the majority
were females (80.5 %). Gallstone-related disease was the most common indication
for BI and managed more often with primary endoscopic management (2,146 vs.
1,132, P < 0.01). Inpatient mortality was not significantly different between
patients undergoing primary endoscopic versus non-endoscopic BI (0.2 % vs. 0.7 %,
P = 0.2). Patients with sepsis were significantly more likely to incur failed
primary endoscopic BI (OR 2.74, 95 % CI 1.15, 6.53) and were more likely to be
managed with non-endoscopic BI (OR 2.13, 95 % CI 1.3, 3.5). Primary non
endoscopic BI and failed endoscopic BI were both associated with longer LOS (by
1.77 days, P < 0.01 and by 2.17 days, P < 0.01, respectively) and higher
hospitals charges (by $11,400, P < 0.01 and by $ 14,200, P < 0.01,
respectively). Conclusion: Primary endoscopic management may be a safe and cost
effective approach for patients with prior BRS who need BI. While primary
endoscopic biliary intervention is more common, primary non-endoscopic
intervention may be used more often for sepsis.
PMID- 29340295
TI - Usage characteristics and adverse event rates of the direct puncture and pull
techniques for percutaneous endoscopic gastrostomy in patients with malignant
tumors of the upper aerodigestive tract.
AB - Background and study aims: Patients with malignant tumors of the upper
gastrointestinal tract are at risk of weight loss. Early supportive nutrition
therapy is therefore recommended and usually requires placement of a percutaneous
endoscopic gastrostomy (PEG). The aim of this study was to compare adverse events
and usage characteristics of the direct puncture technique with those of the
traditional pull technique when used in patients with endoscopically passable
tumors. The primary endpoint was the rate of inflammatory adverse events (AEs) at
the gastrostomy fistula. The secondary endpoint was the long-term rate of
puncture-site metastases. Patients and methods: One hundred twenty patients
(median age 56; IQR 36, 86 years) were randomized and treated per protocol in
this prospective open randomized single-center study. Follow-ups were conducted
on the third and seventh post-interventional days, after 1, 3 and 6 months and
the last follow-up 5 years after intervention. Results: Within the short-term
follow-up period of 6 months after PEG placement, AEs were noted in 47 patients
(39.2 %). These included 22 inflammations and 16 device dislocations and were
mainly found in the puncture group (33 vs. 14 in the pull group) with a
significantly increased incidence in the first month after PEG insertion ( P =
0.001). Evaluation of the 5-year data did not reveal any significant differences.
The gastrostomy tube was used in 101 patients (84.2 %) (range 18 days to 5
years). Conclusions: Our results favor the pull technique for patients with
endoscopically passable tumors of the upper gastrointestinal tract due to less
short-term adverse events. Both systems contributed equally to secure long-term
use.
PMID- 29340296
TI - Risk of colonic diverticular rebleeding according to endoscopic appearance.
AB - Background and study aims: Re-commencement of bleeding (rebleeding) of colonic
diverticula after endoscopic hemostasis is a clinical problem. This study aimed
to examine whether endoscopic visibility of colonic diverticular bleeding affects
the risk of rebleeding after endoscopic hemostasis. Patients and methods: We
performed a retrospective review of endoscopic images and medical charts of
patients with colonic diverticular bleeding who underwent endoscopic hemostasis.
Endoscopic visibility was classified into two types according to visibility of
the source of bleeding; source invisibility due to bleeding or attached hematin
(type 1), or endoscopically visible responsive vessels (type 2). Rebleeding rates
within one year after initial hemostasis were examined. Results: Of 93 patients
with successful endoscopic hemostasis, 38 (41 %) showed type 1 visibility, while
the remaining presented type 2. All patients received hemostasis with clipping,
rebleeding developed in 20 patients (22 %). Type 1 visibility was more likely to
be observed in patients with rebleeding (65 % vs. 34 %, P = 0.013). Multivariate
analysis revealed that after endoscopic hemostasis, type 1 visibility (invisible
source) was the only independent risk factor for colonic diverticular rebleeding
(odds ratio, 3.05; 95 % confidence interval, 1.03 - 9.59, P = 0.044). Kaplan
Meier curve showed the cumulative incidence of rebleeding was significantly
higher in patients with type 1 visibility than those with type 2 visibility ( P
= 0.0033, log-rank test). Conclusion: Hemostasis by clipping for colonic
diverticular bleeding without definite observation of the source of bleeding may
not be sufficiently effective. Other hemostatic methods, including band ligation,
should be considered when the source of bleeding is unclear.
PMID- 29340297
TI - Acetic acid-guided biopsies in Barrett's surveillance for neoplasia detection
versus non-targeted biopsies (Seattle protocol): A feasibility study for a
randomized tandem endoscopy trial. The ABBA study.
AB - Background and study aims : Barrett's esophagus is a potentially pre-cancerous
condition, affecting 375,000 people in the UK. Patients receive a 2-yearly
endoscopy to detect cancerous changes, as early detection and treatment results
in better outcomes. Current treatment requires random mapping biopsies along the
length of Barrett's, in addition to biopsy of visible abnormalities. As only 13 %
of pre-cancerous changes appear as visible nodules or abnormalities, areas of
dysplasia are often missed. Acetic acid chromoendoscopy (AAC) has been shown to
improve detection of pre-cancerous and cancerous tissue in observational studies,
but no randomized controlled trials (RCTs) have been performed to date. Patients
and methods : A "tandem" endoscopy cross-over design. Participants will be
randomized to endoscopy using mapping biopsies or AAC, in which dilute acetic
acid is sprayed onto the surface of the esophagus, highlighting tissue through an
whitening reaction and enhancing visibility of areas with cellular changes for
biopsy. After 4 to 10 weeks, participants will undergo a repeat endoscopy, using
the second method. Rates of recruitment and retention will be assessed, in
addition to the estimated dysplasia detection rate, effectiveness of the
endoscopist training program, and rates of adverse events (AEs). Qualitative
interviews will explore participant and endoscopist acceptability of study design
and delivery, and the acceptability of switching endoscopic techniques for
Barrett's surveillance. Results : Endoscopists' ability to diagnose dysplasia in
Barrett's esophagus can be improved. AAC may offer a simple, universally
applicable, easily-acquired technique to improve detection, affording patients
earlier diagnosis and treatment, reducing endoscopy time and pathology costs. The
ABBA study will determine whether a crossover "tandem" endoscopy design is
feasible and acceptable to patients and clinicians and gather outcome data to
power a definitive trial.
PMID- 29340298
TI - Efficacy and safety of sedation during endoscopic submucosal dissection of
gastric cancers using a comparative trial of propofol versus midazolam.
AB - Background and study aims : Proper sedation is necessary for the safe and
satisfactory completion of endoscopic submucosal dissection (ESD) for early
gastric cancer. This study was conducted as a comparative trial of efficacy and
safety, comparing propofol-based sedation and midazolam-based sedation during ESD
of early gastric cancer patients. Patients and methods : This study examined 64
lesions in 58 patients treated using ESD with midazolam plus pentazocine between
July 2013 and January 2014 (group M) and 237 lesions in 216 patients treated by
ESD using propofol plus pentazocine between February 2014 and December 2015
(group P). The two groups were compared in terms of the frequency of body
movement during ESD as the primary outcome and in terms of the procedure time, en
bloc resection rate, intraoperative change in cardiorespiratory dynamics, and
postoperative awareness as the secondary outcomes. Body movement was defined as
movement by a patient that required interruption of the procedure or restraint of
the patient's body trunk, and addition of a sedative agent. Results : The median
frequency of body movement during ESD was significantly lower in group P (0
times) than in group M (3 times) ( P < 0.001). No significant difference was
found for the mean procedure time (117 min in group P; 127 min in group M).
Although no significant difference was found in the incidence of hypoxemia,
bradycardia, or bradypnea, the incidence of hypotension was significantly higher
in group P (31.5 %) than in group M (6.9 %) ( P = 0.004). Patients in group P
had significantly higher postoperative awareness immediately after ESD and at 1
hour after ESD ( P = 0.002 and 0.022, respectively). Conclusion : These results
demonstrate the efficacy and safety of propofol-based sedation for gastric ESD.
PMID- 29340299
TI - Prospective study of the feasibility of point-of-care testing strategy for
carbapenem-resistant organism detection.
AB - Background/aims: In an investigator-initiated, prospective study, we evaluated
the feasibility of a five-gene sequence point-of-care (POC) testing strategy
(Xpert CARBA-R Assay, Cepheid Inc., Sunnyvale, CA, USA), compared to reference
laboratory PCR (48 - 72 hours turnaround time, two gene sequences), in patients
undergoing endoscopic retrograde cholangiopancreatography (ERCP) and in a
hospital outbreak investigation. Methods: After informed consent, patients
undergoing ERCP (September 2015 - April 2016, n = 191) at Mayo Clinic and
potential hospital contacts (n = 9) of an index carbapenem-resistant organism
(CRO)-positive inpatient were included. Two rectal swabs, one each for reference
and POC assays were obtained. The Xpert CARBA-R Assay enables qualitative rapid
detection of five beta-lactamase gene sequences associated with carbapenem-non
susceptibility in Gram-negative bacteria. Feasibility parameters (specimen
processing and assay run time, ease of use) and percent agreement between the
tests were calculated using JMP Pro11 (SAS Corp, Cary, NC, USA). Results: Mean
age was 62 +/- 15 years; 108 (54 %) were male. Both tests were successfully
performed in all patients. The POC test was rated by endoscopy nurses as
easy/very easy to conduct in 193 patients (97 %); median assay run time and
median time for specimen collection and processing were 55 minutes (interquartile
range IQR: 53 - 55 minutes) and 3 minutes (IQR: 3 - 6 minutes), respectively. In
200/201 (99.5 %) tests, there was agreement between the POC and reference PCR.
Conclusions: The more comprehensive POC CRO testing of patients in the endoscopy
suite is feasible and results are available in < 1 hour. This strategy may enable
rapid risk stratification of duodenoscope exposure to CRO and potentially improve
operational efficiency and decrease costs.
PMID- 29340301
TI - Stable organic thin-film transistors.
AB - Organic thin-film transistors (OTFTs) can be fabricated at moderate temperatures
and through cost-effective solution-based processes on a wide range of low-cost
flexible and deformable substrates. Although the charge mobility of state-of-the
art OTFTs is superior to that of amorphous silicon and approaches that of
amorphous oxide thin-film transistors (TFTs), their operational stability
generally remains inferior and a point of concern for their commercial
deployment. We report on an exhaustive characterization of OTFTs with an
ultrathin bilayer gate dielectric comprising the amorphous fluoropolymer CYTOP
and an Al2O3:HfO2 nanolaminate. Threshold voltage shifts measured at room
temperature over time periods up to 5.9 * 105 s do not vary monotonically and
remain below 0.2 V in microcrystalline OTFTs (MUc-OTFTs) with field-effect
carrier mobility values up to 1.6 cm2 V-1 s-1. Modeling of these shifts as a
function of time with a double stretched-exponential (DSE) function suggests that
two compensating aging mechanisms are at play and responsible for this high
stability. The measured threshold voltage shifts at temperatures up to 75 degrees
C represent at least a one-order-of-magnitude improvement in the operational
stability over previous reports, bringing OTFT technologies to a performance
level comparable to that reported in the scientific literature for other
commercial TFTs technologies.
PMID- 29340300
TI - Shared Mechanisms in the Estimation of Self-Generated Actions and the Prediction
of Other's Actions by Humans.
AB - The question of how humans predict outcomes of observed motor actions by others
is a fundamental problem in cognitive and social neuroscience. Previous
theoretical studies have suggested that the brain uses parts of the forward model
(used to estimate sensory outcomes of self-generated actions) to predict outcomes
of observed actions. However, this hypothesis has remained controversial due to
the lack of direct experimental evidence. To address this issue, we analyzed the
behavior of darts experts in an understanding learning paradigm and utilized
computational modeling to examine how outcome prediction of observed actions
affected the participants' ability to estimate their own actions. We recruited
darts experts because sports experts are known to have an accurate outcome
estimation of their own actions as well as prediction of actions observed in
others. We first show that learning to predict the outcomes of observed dart
throws deteriorates an expert's abilities to both produce his own darts actions
and estimate the outcome of his own throws (or self-estimation). Next, we
introduce a state-space model to explain the trial-by-trial changes in the darts
performance and self-estimation through our experiment. The model-based analysis
reveals that the change in an expert's self-estimation is explained only by
considering a change in the individual's forward model, showing that an
improvement in an expert's ability to predict outcomes of observed actions
affects the individual's forward model. These results suggest that parts of the
same forward model are utilized in humans to both estimate outcomes of self
generated actions and predict outcomes of observed actions.
PMID- 29340302
TI - Localized concentration reversal of lithium during intercalation into
nanoparticles.
AB - Nanoparticulate electrodes, such as Li x FePO4, have unique advantages over their
microparticulate counterparts for the applications in Li-ion batteries because of
the shortened diffusion path and access to nonequilibrium routes for fast Li
incorporation, thus radically boosting power density of the electrodes. However,
how Li intercalation occurs locally in a single nanoparticle of such materials
remains unresolved because real-time observation at such a fine scale is still
lacking. We report visualization of local Li intercalation via solid-solution
transformation in individual Li x FePO4 nanoparticles, enabled by probing sub
angstrom changes in the lattice spacing in situ. The real-time observation
reveals inhomogeneous intercalation, accompanied with an unexpected reversal of
Li concentration at the nanometer scale. The origin of the reversal phenomenon is
elucidated through phase-field simulations, and it is attributed to the presence
of structurally different regions that have distinct chemical potential
functions. The findings from this study provide a new perspective on the local
intercalation dynamics in battery electrodes.
PMID- 29340303
TI - Highly mobile charge-transfer excitons in two-dimensional WS2/tetracene
heterostructures.
AB - Charge-transfer (CT) excitons at heterointerfaces play a critical role in light
to electricity conversion using organic and nanostructured materials. However,
how CT excitons migrate at these interfaces is poorly understood. We investigate
the formation and transport of CT excitons in two-dimensional WS2/tetracene van
der Waals heterostructures. Electron and hole transfer occurs on the time scale
of a few picoseconds, and emission of interlayer CT excitons with a binding
energy of ~0.3 eV has been observed. Transport of the CT excitons is directly
measured by transient absorption microscopy, revealing coexistence of delocalized
and localized states. Trapping-detrapping dynamics between the delocalized and
localized states leads to stretched-exponential photoluminescence decay with an
average lifetime of ~2 ns. The delocalized CT excitons are remarkably mobile with
a diffusion constant of ~1 cm2 s-1. These highly mobile CT excitons could have
important implications in achieving efficient charge separation.
PMID- 29340304
TI - Pressure-induced shear and interlayer expansion in Ti3C2 MXene in the presence of
water.
AB - Pseudo-negative compressibility in layered materials is a phenomenon typically
limited to in situ high-pressure experiments in some clay minerals and carbon
based materials. We show that the MXene Ti3C2T x expands along its
crystallographic c direction when compressed in the presence of H2O. This
expansive effect occurs when a mixture of powders and excess water is quasi
hydrostatically compressed in a diamond anvil cell; it also occurs to a much
larger extent when powders are pressed uniaxially into discs and, notably,
persists after pressure is released. We attribute the expansion to the insertion
of H2O molecules and have identified shear-induced slipping of the nanosheets
comprising multilayered MXene particles as a possible cause of this behavior in
the latter case. This both has implications for the processing of MXenes and
contributes to the field of materials with pseudo-negative compressibility by
adding a new member for further investigation.
PMID- 29340305
TI - Successful Drug-eluting Stent Implantation in a Male Patient with Dextrocardia: A
Case Report.
AB - Situs inversus with dextrocardia is a rare condition, with complete transposition
of all the body organs, including the heart. Percutaneous coronary intervention
(PCI) in these patients is technically difficult because of the mirror image of
organs. Here, we describe a 56-year-old man with coronary heart disease with
known situs inversus with dextrocardia and coronary percutaneous intervention was
performed for stenosis in the right coronary artery. A drug eluting stent was
implanted at this site successfully. This case suggested that the interventional
management of such patients follows the same general rules as for non
dextrocardia patients, but the manipulation of the catheter and projection
position choices need to be taken into consideration to obtain optimal benefits
for the patient.
PMID- 29340306
TI - Iron Chelation Resulting in Renal Phosphate Wasting.
PMID- 29340307
TI - A Patient With CKD Develops Cholestatic Liver Injury During a Clinical Trial.
PMID- 29340308
TI - Noninfectious Peritoneal Dialysis Exit Site Rash-An Unusual Case Report and
Review of the Literature.
PMID- 29340309
TI - Strongyloides stercoralis-Associated Tip Variant Focal Segmental
Glomerulosclerosis.
PMID- 29340310
TI - Disseminated Adenovirus Nephritis After Kidney Transplantation.
PMID- 29340311
TI - Hyponatremia and the Brain.
AB - Hyponatremia is defined by low serum sodium concentration and is the most common
electrolyte disorder encountered in clinical practice. Serum sodium is the main
determinant of plasma osmolality, which, in turn, affects cell volume. In the
presence of low extracellular osmolality, cells will swell if the adaptation
mechanisms involved in the cell volume maintenance are inadequate. The most
dramatic effects of hyponatremia on the brain are seen when serum sodium
concentration decreases in a short period, allowing little or no adaptation. The
brain is constrained inside a nonextensible envelope; thus, brain swelling
carries a significant morbidity because of the compression of brain parenchyma
over the rigid skull. Serum sodium concentration is an important determinant of
several biological pathways in the nervous system, and recent studies have
suggested that hyponatremia carries a significant risk of neurological impairment
even in the absence of brain edema. The brain can also be affected by the
treatment of hyponatremia, which, if not undertaken cautiously, could lead to
osmotic demyelination syndrome, a rare demyelinating brain disorder that occurs
after rapid correction of severe hyponatremia. This review summarizes the
pathophysiology of brain complications of hyponatremia and its treatment.
PMID- 29340312
TI - CKD Screening and Surveillance in Australia: Past, Present, and Future.
AB - Chronic kidney disease (CKD) was largely a hidden health problem until the
publication of an internationally agreed approach to its identification,
monitoring, and treatment. The 2002 National Kidney Foundation CKD classification
and the subsequent 2006 Kidney Disease Improving Global Outcomes (KDIGO)
recommendations are powerful tools for translating thinking about CKD into
clinical practice. These guidelines were strongly endorsed by the international
community, including Australia, and were incorporated into CKD practice
guidelines. In the past, CKD research studies in Australia focused on screening
the general population, and more specifically, individuals at risk for CKD.
Information from these studies led to the recognition that the CKD burden in
Australia is a public health problem and contributed to the development of
national health policies and priorities. At present, apart from the Australia and
New Zealand Dialysis and Transplant Registry (ANZDATA) that reports on CKD
patients undergoing renal replacement therapy (RRT), long-term surveillance to
describe the natural history of the CKD population not on RRT has only recently
started. Entities such as CKD. Queensland and the Western Australian Nephrology
Database are able to fill the gap and provide opportunities for collaborative
research of CKD in Australia. Establishment of a National Health and Medical
Research Centre-funded CKD Centre of Excellence in 2015 and the Better Evidence
and Translation-Chronic Kidney Disease in 2016 are likely to change the future of
CKD surveillance and research in Australia.
PMID- 29340313
TI - Treatment of Severe Hyperkalemia: Confronting 4 Fallacies.
AB - Severe hyperkalemia is a medical emergency that can cause lethal arrhythmias.
Successful management requires monitoring of the electrocardiogram and serum
potassium concentrations, the prompt institution of therapies that work both
synergistically and sequentially, and timely repeat dosing as necessary. It is of
concern then that, based on questions about effectiveness and safety, many
physicians no longer use 3 key modalities in the treatment of severe
hyperkalemia: sodium bicarbonate, sodium polystyrene sulfonate (Kayexalate
[Concordia Pharmaceuticals Inc., Oakville, ON, Canada], SPS [CMP Pharma,
Farmville, NC]), and hemodialysis with low potassium dialysate. After reviewing
older reports and newer information, I believe that these exclusions are ill
advised. In this article, I briefly discuss the treatment of severe hyperkalemia
and detail why these modalities are safe and effective and merit inclusion in the
treatment of severe hyperkalemia.
PMID- 29340314
TI - DNAJB9 Is a Specific Immunohistochemical Marker for Fibrillary
Glomerulonephritis.
AB - Introduction: Fibrillary glomerulonephritis (FGN) is a rare disease with unknown
pathogenesis and a poor prognosis. Until now, the diagnosis of this disease has
required demonstration of glomerular deposition of randomly oriented fibrils by
electron microscopy that are Congo red negative and stain with antisera to Igs.
We recently discovered a novel proteomic tissue biomarker for FGN, namely,
DNAJB9. Methods: In this work, we developed DNAJB9 immunohistochemistry and
tested its sensitivity and specificity for the diagnosis of FGN. This testing was
performed on renal biopsy samples from patients with FGN (n = 84), amyloidosis (n
= 21), a wide variety of non-FGN glomerular diseases (n = 98), and healthy
subjects (n = 11). We also performed immunoelectron microscopy to determine
whether DNAJB9 is localized to FGN fibrils. Results: Strong, homogeneous, smudgy
DNAJB9 staining of glomerular deposits was seen in all but 2 cases of FGN. The 2
cases that did not stain for DNAJB9 were unique, as they had glomerular staining
for IgG only (without kappa or lambda) on immunofluorescence. DNAJB9 staining was
not observed in cases of amyloidosis, in healthy subjects, or in non-FGN
glomerular diseases (with the exception of very focal staining in 1 case of
smoking-related glomerulopathy), indicating 98% sensitivity and > 99%
specificity. Immunoelectron microscopy showed localization of DNAJB9 to FGN
fibrils but not to amyloid fibrils or immunotactoid glomerulopathy microtubules.
Conclusion: DNAJB9 immunohistochemistry is sensitive and specific for FGN.
Incorporation of this novel immunohistochemical biomarker into clinical practice
will now allow more rapid and accurate diagnosis of this disease.
PMID- 29340315
TI - Contrast-Induced Nephropathy and Oxygen Pretreatment in Patients With Impaired
Renal Function.
AB - Introduction: Contrast-induced nephropathy is a complication following coronary
angiography and percutaneous coronary intervention. Because contrast-induced
nephropathy is a predictor of long-term mortality in patients with ischemic heart
disease undergoing percutaneous coronary intervention, preventive strategies are
required. We assessed the effects of periprocedural oxygenation on contrast
induced nephropathy among patients with pre-existing renal dysfunction. Methods:
A total of 200 consecutive patients with impaired renal function (estimated
glomerular filtration < 60 ml/min per 1.73 m2) undergoing elective cardiovascular
angiography were randomly assigned to an oxygenation treatment (n = 100) or
control group (n = 100). In oxygenation treatment, pure oxygen (2 L/min) was
administered for 10 minutes before exposure to contrast medium. The primary
endpoint was the incidence of contrast-induced nephropathy, defined as a >= 25%
increase in serum creatinine levels from baseline within 48 hours of exposure.
Results: In the oxygenation treatment group, partial pressure of arterial oxygen
was higher (135 +/- 25 mm Hg vs. 84 +/- 10 mm Hg, P < 0.001); contrast-induced
nephropathy incidence was lower (1% vs. 8%, odds ratio [OR] = 0.12, 95%
confidence interval [CI] = 0.01-0.95, P = 0.02); and partial pressure of arterial
carbon dioxide and bicarbonate base lactate levels were similar compared with
those in the control group. Upon univariate analysis, excess and absence of
oxygenation treatment (OR = 9.18, CI = 1.13-74.86, P = 0.03) and anemia (OR =
4.30, CI = 1.04-17.78, P = 0.04) were shown to be associated with contrast
induced nephropathy incidence. Conclusion: Oxygenation, a simple,
nonpharmacological strategy, may be beneficial when using contrast media in
patients with impaired renal function from noninvasive angiography to emergency
catheterization.
PMID- 29340316
TI - NPT-IIb Inhibition Does Not Improve Hyperphosphatemia in CKD.
AB - Introduction: Serum phosphate levels are insufficiently controlled in many
patients with end-stage renal disease (ESRD), and novel therapeutic strategies
are needed. Blocking intestinal phosphate absorption mediated by sodium-dependent
phosphate co-transporter type 2b (NPT-IIb) holds promise; thus, we evaluated the
efficacy, safety, tolerability, and pharmacokinetics of the novel and specific
small molecule NPT-IIb inhibitor ASP3325 for the first time in humans. Methods:
We conducted a randomized, double-blind, placebo-controlled, phase 1a single (n =
88) and multiple (n = 36) ascending dose study in healthy subjects, and a
randomized, open-label, uncontrolled, phase 1b study in hyperphosphatemic ESRD
patients on hemodialysis (single oral dose, n = 5; multiple oral doses, n = 17).
Primary efficacy measures were urinary phosphate and fecal phosphorous excretion
(healthy subjects) and serum phosphate level (ESRD patients). Results: No time-
or dose-dependent changes in urinary phosphate or fecal phosphorous excretion
were observed following single/multiple ASP3325 doses for 7 days in healthy
subjects. In ESRD patients, ASP3325 administered 3 times daily for 2 weeks before
or after a meal did not reduce serum phosphate levels. ASP3325 was safe and well
tolerated in both populations. Conclusion: NPT-IIb inhibition with ASP3325 was
not effective in reducing serum phosphate levels in ESRD patients. The relevance
of NPT-IIb in humans and feasibility of oral NPT-IIb inhibitors for treatment of
hyperphosphatemia in ESRD remain uncertain.
PMID- 29340318
TI - APOL1 Risk Variants Independently Associated With Early Cardiovascular Disease
Death.
AB - Introduction: The relationship of APOL1 renal risk variants to cardiovascular
disease (CVD) is controversial and was the subject of this investigation.
Methods: Age, cause of death, and nephrosclerosis (the latter defined by
glomerulosclerosis) were analyzed in the autopsies of 162 African Americans and
136 whites genotyped for APOL1 risk alleles. Results: Sudden deaths represented
>75% of CVD autopsies for both races and all-risk genotypes. The average ages of
CVD deaths for African Americans with 1 and 2 APOL1 risk alleles were,
respectively, 7.0 years (P = 0.02) and 12.2 years (P < 0.01) younger than African
Americans with 0 risk alleles and 8.7 years (P = 0.01) and 13.9 years (P = 0.01)
younger than whites. Age differences were not significant between African
Americans and whites with 0 risk alleles (P = 0.61). The younger CVD deaths of
African Americans were associated with less severe glomerulosclerosis with 2 (P =
0.01), although not 1 (P = 0.09), compared with 0 APOL1 risk alleles.
Cardiomyopathy was found in 23% of African Americans with 1 and 2 risk alleles
and significantly contributed to the lower age (P = 0.01). For non-CVD deaths,
age differences were not seen by race (P = 0.28) or among African Americans by
risk allele status (P = 0.38). Conclusion: Carriage of 1 or 2 APOL1 risk alleles
in African Americans was associated with earlier age deaths due to coronary
artery disease and cardiomyopathy. For 2 risk alleles, the early age was
independent of nephrosclerosis.
PMID- 29340317
TI - Intradialytic Cognitive and Exercise Training May Preserve Cognitive Function.
AB - Introduction: Cognitive decline is common and increases mortality risk in
hemodialysis patients. Intradialytic interventions like cognitive training (CT)
and exercise training (ET) may preserve cognitive function. Methods: We conducted
a pilot randomized controlled trial of 20 hemodialysis patients to study the
impact of 3 months of intradialytic CT (tablet-based brain games) (n = 7), ET
(foot peddlers) (n = 6), or standard of care (SC) (n = 7) on cognitive function.
Global cognitive function was measured by the Modified Mini Mental Status Exam
(3MS), psychomotor speed was measured by Trail Making Tests A and B (TMTA and
TMTB), and executive function was assessed by subtracting (TMTB - TMTA). Lower
3MS scores and slower TMTA and TMTB times reflected worse cognitive function. P
values for differences were generated using analysis of variance, and 95%
confidence intervals (CIs) and P values were generated from linear regression.
Results: Patients with SC experienced a decrease in psychomotor speed and
executive function by 3 months (TMTA: 15 seconds; P = 0.055; TMTB: 47.4 seconds;
P = 0.006; TMTB - TMTA; 31.7 seconds; P = 0.052); this decline was not seen among
those with CT or ET (all P > 0.05). Compared with SC, the difference in the mean
change in 3MS score was -3.29 points (95% CI: -11.70 to 5.12; P = 0.42) for CT
and 4.48 points (95% CI: -4.27 to 13.22; P = 0.30) for ET. Compared with SC, the
difference in mean change for TMTA was -15.13 seconds (95% CI: -37.64 to 7.39; P
= 0.17) for CT and -17.48 seconds (95% CI: -41.18 to 6.22; P = 0.14) for ET, for
TMTB, the difference was -46.72 seconds (95% CI: -91.12 to -2.31; P = 0.04) for
CT and -56.21 seconds (95% CI: -105.86 to -6.56; P = 0.03) for ET, and for TMTB -
TMTA, the difference was -30.88 seconds (95% CI: -76.05 to 14.28; P = 0.16) for
CT and -34.93 seconds (95% CI: -85.43 to 15.56; P = 0.16) for ET. Conclusion:
Preliminary findings of our pilot study suggested that cognitive decline in
psychomotor speed and executive function is possibly prevented by intradialytic
CT and ET. These preliminary pilot findings should be replicated.
PMID- 29340319
TI - Life Expectancy for Patients From the Southeastern United States With IgA
Nephropathy.
AB - Introduction: Although end-stage renal disease (ESRD) and surrogate markers for
renal dysfunction are frequently used as outcome markers for IgA nephropathy, the
clinical course after reaching ESRD is not well documented. This study examined
outcomes of progression to ESRD and age at death in a cohort of adults with IgA
nephropathy with a long duration of follow-up. Methods: Patient and kidney
survival of 251 adult patients with IgA nephropathy from the southeastern United
States diagnosed between January 1, 1976 and December 31, 2005 were analyzed.
Results: Median age at diagnosis was 36.9 years. Most patients were men (69%) and
Caucasian (95%). Only 46% had an estimated glomerular filtration rate >60 ml/min
per 1.73 m2 at diagnosis. Mean follow-up time from time of diagnostic biopsy to
death or end of study was 19.3 years. Of 251 patients, 132 (53%) progressed to
ESRD and 97 (39%) died. Life expectancy was reduced by 10.1 years, with a median
observed age of death at 65.7 years and a median expected age at death of 75.8
years. Eighty-three percent of the deaths occurred after progression to ESRD.
Conclusion: Life expectancy is substantially reduced for patients diagnosed with
IgA nephropathy in the southeastern United States.
PMID- 29340320
TI - Association of a Low-Protein Diet With Slower Progression of CKD.
AB - Introduction: Reducing protein intake is recommended for slowing chronic kidney
disease (CKD) progression, but assessment of its true effectiveness is sparse.
Methods: Using the Maroni formula, we assessed dietary protein intake (DPI) from
24-hour urinary urea excretion in 1594 patients (67% men and 33% women) with CKD,
784 of whom also had 7-day food records. Cause-specific hazard ratios (HRs) and
95% confidence intervals for the competing risks of DPI-associated end-stage
renal disease (ESRD) or death were estimated in 1412 patients with baseline
glomerular filtration rate >=15 ml/min per 1.73 m2, measured by 51Cr-EDTA renal
clearance (mGFR). Results: Overall, mean DPI estimated from urea excretion was
1.09 +/- 0.30 g/kg of body weight per day (range = 0.34-2.76); 20% of patients
had values > 1.3 g/kg per day, and 1.9% had values < 0.6 g/kg per day. Urea
excretion and food records produced similar estimates of mean DPI. The lower the
mGFR, the lower the mean DPI. Over a median follow-up of 5.6 years, there were
319 ESRD events and 189 pre-ESRD deaths. After adjusting for relevant covariates,
each 0.1 g/kg daily higher baseline urea excretion-based DPI or food record-based
DPI was associated with an HR for ESRD of 1.05 (95% confidence interval 1.01
1.10) or 1.09 (95% confidence interval 1.04-1.14), respectively. HRs were
stronger in patients with baseline mGFR < 30 ml/min per 1.73 m2. There was no
association with mortality. The mean age of the patients was 59 +/- 15 years, and
mean body mass index was 26.6 +/- 5.2 kg/m2. Conclusion: In this prospective
observational study, the lower the baseline DPI, the slower the progression
toward ESRD. Most importantly, the absence of threshold for the relation between
DPI and ESRD risk indicates that there is no optimal DPI in the range observed in
this cohort.
PMID- 29340321
TI - Randomized Clinical Trial Design to Assess Abatacept in Resistant Nephrotic
Syndrome.
AB - Introduction: Treatment-resistant nephrotic syndrome is a rare form of glomerular
disease that occurs in children and adults. No Food and Drug Administration
approved treatments consistently achieve remission of proteinuria and
preservation of kidney function. CD80 (B7-1) can be expressed on injured
podocytes, and administration of abatacept (modified CTLA4-Ig based on a natural
ligand to CD80) has been associated with sustained normalization of urinary
protein excretion and maintenance of glomerular filtration rate in experimental
and clinical settings. Methods: In this report, we describe the rationale for and
design of a randomized, placebo-controlled, clinical trial of abatacept in
patients with treatment-resistant nephrotic syndrome caused by focal segmental
glomerulosclerosis or minimal change disease. The design is a hybrid of a
parallel-group and crossover design (switchover) with the primary objectives
assessed in the first period of the study and the secondary objectives assessed
using data from both periods. All participants will receive the active agent in 1
of the periods. The duration of treatment will be 4 months per period. Results:
The primary outcome will be improvement in nephrotic-range proteinuria to
subnephrotic range, that is, reduction from baseline to 4 months in urine
protein:creatinine ratio >= 50% and to a level < 3. The projected sample size is
90 patients, which has 80% power to detect a treatment difference of 28%.
Conclusion: This study advances efforts to validate CD80 as a therapeutic target
for treatment-resistant nephrotic syndrome, and implements a precision medicine
based approach to this serious kidney condition in which the selection of a
therapeutic agent is guided by the underlying disease mechanism operating in
individual patients.
PMID- 29340322
TI - Paricalcitol Versus Calcifediol for Treating Hyperparathyroidism in Kidney
Transplant Recipients.
AB - Introduction: Secondary hyperparathyroidism (SHPT) and vitamin D deficiency are
common at kidney transplantation and are associated with some early and late
complications. This study was designed to evaluate whether paricalcitol was more
effective than nutritional vitamin D for controlling SHPT in de novo kidney
allograft recipients. Methods: This was a 6-month, investigator-initiated,
multicenter, open-label, randomized clinical trial. Patients with
pretransplantation iPTH between 250 and 600 pg/ml and calcium <10 mg/dl were
randomized to paricalcitol (PAR) or calcifediol (CAL). The intention-to-treat
population (PAR: n = 46; CAL: n = 47) was used for the analysis. The primary
endpoint was the percentage of patients with serum iPTH >110 pg/ml at 6 months.
Secondary endpoints were bone mineral metabolism, renal function, and allograft
protocol biopsies. Results: The primary outcome occurred in 19.6% of patients in
the PAR group and 36.2% of patients in the CAL group (P = 0.07). However, there
was a higher percentage of patients with iPTH <70 pg/ml in the PAR group than in
the CAL group (63.4% vs. 37.2%; P = 0.03). No differences were observed in bone
turnover biomarkers and bone mineral density. The estimated glomerular filtration
rate was significantly higher in the CAL group than in the PAR group without
differences in albuminuria. In protocol biopsies, interstitial fibrosis and
tubular atrophy tended to be higher in the PAR group than in the CAL group (48%
vs. 23.8%; P = 0.09). Both medications were well tolerated. Conclusion: Both PAR
and CAL reduced iPTH, but PAR was associated with a higher proportion of patients
with iPTH <70 pg/ml. These results do not support the use of PAR to treat
posttransplantation hyperparathyroidism.
PMID- 29340323
TI - Clinical and Pathological Significance of Autoantibodies to Erythropoietin
Receptor in Type 2 Diabetic Patients With CKD.
AB - Introduction: We examined the impact of autoantibodies on the erythropoietin
receptor (EPOR) in type 2 diabetic patients with chronic kidney disease (CKD).
Methods: A total of 112 Japanese patients with type 2 diabetes who had CKD were
enrolled in this study and followed for a mean of 45 months. Sera from these
patients were screened for anti-EPOR antibodies using enzyme-linked immunosorbent
assays. Results: Anti-EPOR antibodies were detected in 26 patients (23%). Anti
EPOR antibodies were associated with low hemoglobin concentrations and decreased
renal function. In patients with biopsy-proven diabetic nephropathy, anti-EPOR
antibodies were associated with increased levels of interstitial inflammation. A
decrease in renal function was observed more frequently in patients with
antibodies than in those without antibodies, and the presence of the antibodies
together with well-known clinical parameters, including proteinuria and low
glomerular filtration rate, was a significant risk factor for end-stage renal
disease. In human tubular epithelial HK-2 cells, IgG fractions containing anti
EPOR antibodies upregulated the expression of monocyte chemoattractant protein-1
mRNA under a high concentration of glucose. Conclusion: Anti-EPOR antibodies
might be involved in the progression of renal lesions and in the impaired
erythropoiesis in type 2 diabetic patients with CKD. Furthermore, the presence of
anti-EPOR antibodies may be an additional predictor for end-stage renal disease
in type 2 diabetes.
PMID- 29340324
TI - Temporal Association Between PLA2R Antibodies and Clinical Outcomes in Primary
Membranous Nephropathy.
AB - Introduction: Autoantibodies to M-type phospholipase A2 receptor (aPLA2R) are
seen in two-thirds of patients with primary membranous nephropathy (PMN) and are
associated with disease activity. However, the precise temporal dynamics between
the presence and amount of aPLA2R in circulation, as well as the clinical
activity, are not known. We evaluated the temporal association between disease
activity and serum aPLA2R during and after treatment in PMN. Methods: The study
included all patients with PMN and elevated aPLA2R who were started on
immunosuppressive therapy for persistent nephrotic syndrome at a single center
between December 2014 and December 2015. Serum samples were tested for aPLA2R at
baseline and at monthly intervals for 6 months. Clinical details were collected
monthly for 9 months. Serological remission was defined as negative aPLA2R in 2
consecutive samples. Clinical remission was defined by standard criteria.
Results: A total of 30 patients with PMN were studied. Of these, 28 (93%) had
elevated levels at baseline, whereas 2 (7%) became positive after 1 month. The
mean age was 33.2 +/- 1 (range, 13-52) years. Median baseline aPLA2R titer was
163.41 (range, 70-291.01) RU/ml. A total of 24 patients (80%) achieved
serological remission by 6 months. Among all the serological responders, 54% had
achieved negative aPLA2R by the end of the first month. Clinical remission was
observed in 20 patients (67%). Serological and clinical remission were noted at
2.7 +/- 1.71 and 5.05 +/- 2.64 months, respectively. Conclusion: In patients with
aPLA2R-associated PMN, reduction in circulating aPLA2R precedes clinical
remission. Persistence of aPLA2R at the end of therapy is associated with
clinical resistance.
PMID- 29340325
TI - End-Stage Kidney Disease From Scleroderma in the United States, 1996 to 2012.
AB - Introduction: Although the management of scleroderma continues to evolve, it is
unknown whether the burden of end-stage kidney disease (ESKD) treated with
maintenance renal replacement therapy from SD has changed. Methods: We examined
United States Renal Data System data (n = 1,677,303) for the years 1996 to 2012
to quantify the incidence and outcomes of ESKD from scleroderma treated with
renal replacement therapy (n = 2398). Outcomes assessed through demography
matched scleroderma-positive/scleroderma-negative comparisons included recovery
of kidney function, mortality, listing for transplant, renal transplantations,
and graft failure. Results: Overall ESKD rates from scleroderma were 0.5 per
million per year. Adjusted incidence ratios fell over time, to 0.42 in 2012 (vs.
1996, 95% confidence interval [CI] = 0.32-0.54, P < 0.001). Adjusted incidence
ratios for ESKD from scleroderma fell over time in both sexes, all age, race, and
ethnicity categories except age < 20 years and Asian race, and in all regions of
the United States. After initiating renal replacement therapy, patients with
scleroderma had a greater likelihood of recovery of kidney function (hazards
ratio [HR] = 2.67, 95% CI = 1.90-3.76, P < 0.001) and death (HR = 1.44, 95% CI =
1.34-1.54, P < 0.001) and a lower likelihood of transplantation (HR = 0.51, 95%
CI = 0.44-0.59, P < 0.001) than demography-matched patients without scleroderma.
Conclusion: The incidence of ESKD from scleroderma appears to have declined in
the United States since 1996. ESKD from scleroderma is associated with an
enhanced likelihood of recovery of kidney function and death, a reduced
likelihood of transplantation, and similar outcomes after transplantation.
PMID- 29340326
TI - mTORC1 Inhibition Is an Effective Treatment for Sporadic Renal Angiomyolipoma.
AB - Introduction: Renal angiomyolipoma (AML) is the most common benign renal tumor.
Despite a generally benign histology, AML can result in significant morbidity,
from intra-abdominal hemorrhage and reduction in kidney function. While
classically associated with the autosomal dominant disorder tuberous sclerosis
complex (TSC) or with pulmonary lymphangioleiomyomatosis, most AMLs are sporadic.
Mammalian target of rapamycin complex 1 (mTORC1) inhibitors (e.g., sirolimus)
have been found to be effective in treating TSC- or lymphangioleiomyomatosis
associated AML, but to date it is unknown whether this strategy is effective for
sporadic AML. Methods: We stained tumor specimens of sporadic AML patients for
pS6 to assess for mTORC1 activation. Results: We detected strong activation of
the mTORC1 pathway, similar to TSC-associated AML. Consequently, we showed that
in vitro treatment with sirolimus results in significant growth inhibition of the
human sporadic AML cell line SV7Tert, similar to the effect seen when the same
treatment is applied to the human TSC-associated AML cell line UMBSV-tel. To
further investigate the potential of mTORC1 inhibition for treating sporadic AML
and assess whether the in vitro results are clinically relevant, we identified a
patient with sporadic, bilateral AMLs, showing continued tumor growth following a
partial nephrectomy. Using immunostaining, we detected strong mTORC1 activation
in the patient's AML tissue. Accordingly, upon treatment with sirolimus, we noted
significant reduction in the patient's tumor volume and resolution of
hydronephrosis, without any significant side effects. Conclusion: We propose
mTORC1 inhibition as an effective treatment option for patients with sporadic
AML, which represents the vast majority of patients with this tumor.
PMID- 29340327
TI - Trimethoprim+Sulfamethoxazole Reduces Rates of Melioidosis in High-Risk
Hemodialysis Patients.
AB - Introduction: Melioidosis causes sepsis and death in the Top End of Northern
Australia during the monsoonal wet season. Dialysis-dependent adults suffer
higher melioidosis rates compared to low rates among renal transplant patients
who routinely receive trimethoprim+sulfamethoxazole prophylaxis. Methods: We
performed a prospective interventional study to determine the efficacy and safety
of daily trimethoprim+sulfamethoxazole prophylaxis in hemodialysis patients
during the wet season, from 1 November 2014 to 30 April 2015. Hemodialysis (for
>= 3 months) patients >= 18 years of age were offered treatment. A total of 269
patients on hemodialysis were eligible. Eight of the 269 patients (3%) were
excluded from the analysis for being on melioidosis treatment. In all, 169 of 261
patients (64.8%) received the prophylaxis, and 92 of 261 patients (35.2%) did
not, because of allergy history (n = 10), remoteness and logistical reasons (n =
60), poor dialysis attendance (n = 11), and refusal (n = 11). We monitored for
clinical side effects 3 times weekly and neutropenia, thrombocytopenia, and liver
function monthly throughout treatment and for 2 months posttreatment. Results: In
all, 169 of 261 patients (64.8%) received the prophylaxis. There was no age
(years) difference by group (prophylaxis vs. nonprophylaxis, 54.7 [11.3] vs. 54.3
[11.2] [P = 0.751]). Sixteen of 261 patients (6%) had melioidosis. The event
frequency was 0% (0/169, prophylaxis, vs. 17.4% [16/92, nonprophylaxis], P <
0.001). Higher thrombocytopenia and neutropenia rates were noted in the
prophylaxis group. These did not warrant treatment stoppage. There was no
difference in liver function. Three patients (1.8%) withdrew from the treatment
because of side effects. Conclusion: Daily dosing was effective and safe.
Posthemodialysis dosing in the subsequent seasons was effective and safer. We
recommend this approach in melioidosis-prevalent regions.
PMID- 29340328
TI - Nephrin Loss Can Be Used to Predict Remission and Long-term Renal Outcome in
Patients With Minimal Change Disease.
AB - Introduction: Minimal change disease is a common cause of nephrotic syndrome. In
general, patients with minimal change disease respond to corticosteroids and have
excellent long-term renal survival. However, some patients have less favorable
outcome. These patients are often thought to have progressed to focal segmental
glomerulosclerosis. We previously reported that a segmental loss of podocyte
markers is present before the development of focal segmental glomerulosclerosis
in a rat model. Here, we investigated whether loss of podocyte marker nephrin can
serve as a biomarker for predicting poor outcome in patients with minimal change
disease. Methods: We obtained 47 kidney biopsy samples from patients diagnosed
with minimal change disease and stained sections with periodic acid-Schiff and
for nephrin. Nephrin loss was scored by 2 independent researchers who were
blinded to clinical outcome. Clinical data were collected retrospectively, and
nephrin loss was correlated with clinical follow-up data. Results: Nephrin loss
was present in 34% of the biopsy samples. During follow-up, patients with nephrin
loss achieved remission less frequently (61%) compared to patients without (96%)
(P = 0.002). Moreover, 5-year eGFR was lower in the patients with renal nephrin
loss. The risk of eGFR decreasing to < 60 ml/min per 1.73m2 increased with each
percentage of glomeruli with nephrin loss (hazard ratio = 1.044, 95% confidence
interval = 1.02-1.07). Conclusion: These results indicate that nephrin loss in
patients with minimal change disease can help predict both remission and long
term renal outcome.
PMID- 29340329
TI - A Salivary Urea Nitrogen Dipstick to Detect Obstetric-Related Acute Kidney
Disease in Malawi.
AB - Introduction: Obstetric-related acute kidney injury (AKI) is associated with
adverse outcomes for mother and fetus, particularly in low-income countries.
However, laboratory-independent tools to facilitate diagnosis are lacking. We
assessed the diagnostic performance of a salivary urea nitrogen (SUN) dipstick to
detect obstetric-related acute kidney disease in Malawi. Methods: Women at high
risk for AKI admitted to an obstetric unit in Blantyre, Malawi, were recruited
between 21 September and 11 December 2015. Patients underwent serum creatinine
(SCr) testing alongside measurement of SUN using a dipstick on admission, and
every 48 hours thereafter if evidence of kidney disease was found. Results: A
total of 301 patients were included (mean age 25.9 years, 11% HIV positive). Of
the patients, 23 (7.6%) had AKI, stage 1 in 47.8%, most commonly due to
preeclampsia/eclampsia. Mean presenting SCr values were 108.8 +/- 21.8 MUmol/l
(1.23 +/- 0.25 mg/dl), 118 +/- 34.45 MUmol/l (1.33 +/- 0.39 mg/dl), and 136.1 +/-
30.4 MUmol/l (1.54 +/- 0.34 mg/dl) in AKI stages 1 to 3 respectively. SUN > 14
mg/dl had a sensitivity of 12.82% and a specificity of 97.33% to detect acute
kidney disease; the area under the receiver operating characteristic curve was
0.551. In patients with normal SUN on admission, perinatal mortality was 11.8%,
and was 25.0% if SUN was > 14 mg/dl (P = 0.18). Conclusion: The SUN dipstick was
specific but insensitive when used to diagnose obstetric-related AKI. Limited
biochemical derangement and low salivary urea concentrations due to physiological
changes in pregnancy, as opposed to a technical limitation of the dipstick
itself, are the likely reason for the lack of sensitivity in this study.
PMID- 29340330
TI - Efficacy and Safety of Sucroferric Oxyhydroxide and Calcium Carbonate in
Hemodialysis Patients.
AB - Introduction: In this phase III, open-label, single-arm, multi-center 12-week
study, we evaluated the efficacy and safety of combination therapy with
sucroferric oxyhydroxide (PA21) and calcium carbonate for hemodialysis patients
with hyperphosphatemia. Methods: We enrolled 35 subjects aged >= 20 years with
end-stage kidney disease and serum phosphorus 3.5-6.0 mg/dl who were undergoing
hemodialysis 3 times weekly and taking calcium carbonate and sevelamer
hydrochloride. Patients switched from sevelamer hydrochloride and calcium
carbonate to sucroferric oxyhydroxide and calcium carbonate. Sucroferric
oxyhydroxide was orally administered 3 times daily within 750 mg/d (250 mg per
dose) to 3000 mg/d (1000 mg per dose), immediately before every meal, for 12
weeks. Calcium carbonate was orally administered 3 times daily after every meal.
Outcomes were serum phosphorus concentration, safety, and satisfaction with bowel
movements. Results: Mean (SD) serum phosphorus concentrations were 5.01 (0.63)
mg/dl at week 0 and 4.89 (1.14) mg/dl at the end of treatment, after patients
switched from sevelamer hydrochloride to sucroferric oxyhydroxide. The incidence
of adverse drug reactions was 31.4% (11/35), with diarrhea being the most
frequent (31.4%). More sucroferric oxyhydroxide-treated patients were satisfied
with their bowel movements. More patients with constipation, as well as those who
experienced diarrhea, were satisfied with their bowel movements at the end of the
study. Conclusion: Combined administration of sucroferric oxyhydroxide and
calcium carbonate at low doses was effective in maintaining serum phosphorus
concentrations within the target range, and patients' gastrointestinal status
improved. Sucroferric oxyhydroxide maintained its serum phosphorus-lowering
effect with a decreased pill burden, and its concomitant administration with
calcium carbonate was well tolerated.
PMID- 29340331
TI - Location-Specific Oral Microbiome Possesses Features Associated With CKD.
AB - Introduction: Chronic kidney disease (CKD), a progressive loss of renal function,
can lead to serious complications if underdiagnosed. Many studies suggest that
the oral microbiota plays important role in the health of the host; however,
little is known about the association between the oral microbiota and CKD
pathogenesis. Methods: In this study, we surveyed the oral microbiota in saliva,
the left and right molars, and the anterior mandibular lingual area from 77
participants (18 with and 59 without CKD), and tested their association with CKD
to identify microbial features that may be predictive of CKD status. Results: The
overall oral microbiota composition significantly differed by oral locations and
was associated with CKD status in saliva and anterior mandibular lingual samples.
In CKD patients, we observed a significant enrichment of Neisseria and depletion
of Veillonella in both sample types and a lower prevalence of Streptococcus in
saliva after adjustment for other comorbidities. Furthermore, we detected a
negative association of Neisseria and Streptococcus genera with the kidney
function as measured by estimated glomerular filtration rate. Neisseria abundance
also correlated with plasma interleukin-18 levels. Conclusion: We demonstrate the
association of the oral microbiome with CKD and inflammatory kidney biomarkers,
highlighting a potential role of the commensal bacteria in CKD pathogenesis. A
better understanding of the interplay between the oral microbiota and CKD may
help in the development of new strategies to identify at-risk individuals or to
serve as a novel target for therapeutic intervention.
PMID- 29340332
TI - Endothelial Progenitor Cells and Vascular Health in Dialysis Patients.
PMID- 29340333
TI - Acute Kidney Injury Ascertainment Is Affected by the Use of First Inpatient
Versus Outpatient Baseline Serum Creatinine.
PMID- 29340334
TI - The Authors Reply.
PMID- 29340335
TI - Dialysis Should Be Started When Absolutely Necessary, Not Early and
Incrementally.
PMID- 29340336
TI - Re: Further Evidence Supporting the Accuracy of Quantitative Magnetic Resonance
Imaging for Evaluating Iron Load in Dialysis Patients.
PMID- 29340337
TI - The Author Replies.
PMID- 29340338
TI - The Author Replies.
PMID- 29340339
TI - Other Estimation of Blood Losses in Hemodialysis and Formula for Translating
Liver Iron Concentration From Iron Balance Calculation Based on Iron Removal by
Phlebotomy.
PMID- 29340340
TI - American Geriatrics Society Beers Criteria and Anticoagulant Use in Older Adults
With Renal Impairment.
PMID- 29340341
TI - Credentialing of Hospitalists in Ultrasound-Guided Bedside Procedures: A Position
Statement of the Society of Hospital Medicine.
AB - Ultrasound guidance is used increasingly to perform the following 6 bedside
procedures that are core competencies of hospitalists: abdominal paracentesis,
arterial catheter placement, arthrocentesis, central venous catheter placement,
lumbar puncture, and thoracentesis. Yet most hospitalists have not been certified
to perform these procedures, whether using ultrasound guidance or not, by
specialty boards or other institutions extramural to their own hospitals.
Instead, hospital privileging committees often ask hospitalist group leaders to
make ad hoc intramural certification assessments as part of credentialing. Given
variation in training and experience, such assessments are not straightforward
"sign offs." We thus convened a panel of experts to conduct a systematic review
to provide recommendations for credentialing hospitalist physicians in ultrasound
guidance of these 6 bedside procedures. Pathways for initial and ongoing
credentialing are proposed. A guiding principle of both is that certification
assessments for basic competence are best made through direct observation of
performance on actual patients.
PMID- 29340342
TI - Precision of the Connection Between Implant and Standard or Computer-Aided
Design/Computer-Aided Manufacturing Abutments: A Novel Evaluation Method.
AB - PURPOSE: The aim of this in vitro study was to verify whether or not stock and
computer-aided design/computer-aided manufacturing (CAD/CAM) abutments show
similar precision in the connection with the respective implants. MATERIALS AND
METHODS: Ten CAD/CAM titanium abutments were compared with 10 stock titanium
abutments. Each abutment fit a regular-platform implant (Institute Straumann).
Implants and abutments were measured independently and then connected. During the
connection procedure, the torque was measured using a six-axes load cell. Then,
outer geometric features of the implant-abutment connection were measured again.
Finally, the assembly was sectioned to provide the analysis of inner surfaces in
contact. The geometric measurements were performed using a multisensored opto
mechanical coordinate measuring machine. The following parameters were measured
and compared for the CAD/CAM and stock titanium abutment groups, respectively:
width of interference and interference length between the conical surfaces of the
implant and abutment; and volume of material involved in the implant-abutment
connection. RESULTS: Interference width mean +/- SD values of 18 +/- 0.5 and 14
MU 0.5 MUm were calculated for the stock and CAD/CAM titanium abutment groups,
respectively. The difference was statistically significant (P = .02).
Furthermore, the interference length mean +/- SD values of 763 +/- 10 and 816 +/-
43 MUm were calculated for stock and CAD/CAM titanium abutment groups,
respectively. The difference was also statistically significant (P = .04).
Finally, the volume of material involved in the implant-abutment connection was
compared between stock and CAD/CAM titanium abutment groups; the mean +/- SD
values of 0.134 +/- 0.014 and 0.108 +/- 0.023 mm3 were significantly different (P
= .009). CONCLUSION: Both standard and CAD/CAM abutment groups showed a three
dimensional (3D) seal activation after the screw tightening. Nevertheless, stock
titanium abutments showed a significantly higher volume of material involved in
the implant-abutment connection compared with that of CAD/CAM titanium abutments.
PMID- 29340343
TI - What is the Impact of Epstein-Barr Virus in Peri-implant Infection?
AB - PURPOSE: To compare the qualitative and quantitative profile of Epstein-Barr
virus (EBV) at external and internal implant surfaces between participants with
peri-implantitis and healthy peri-implant tissues and to quantitatively assess
the relation between EBV and periopathogens inside the microbiologic profile
associated with peri-implantitis. MATERIALS AND METHODS: Microbiologic specimens
were retrieved from 84 patients wearing 190 implants to estimate the levels of
EBV and 10 periopathogens in the peri-implant pocket and internal-implant
connection using quantitative polymerase chain reaction. RESULTS: The study
sample consisted of 113 healthy and 77 peri-implantitis-affected implants.
Statistical significance was not reached in EBV prevalence between peri
implantitis and healthy controls. EBV-positive participants demonstrated higher
levels of Prevotella intermedia (Pi) and Campylobacter rectus (Cr) compared with
EBV-negative participants. A positive correlation was demonstrated among EBV and
Tannerella forsythia (Tf), Parvimonas micra (Pm), Fusobacterium nucleatum (Fn),
and Cr levels in peri-implantitis-affected implants, while healthy controls
demonstrated a positive correlation between EBV and Aggregatibacter
actinomycetemcomitans (Aa), Pi, and Pm. CONCLUSION: EBV cannot be considered as a
microbiologic marker of peri-implantitis. However, EBV could be considered as a
risk factor and a peri-implantitis enhancer based on its positive correlations
with pathogens associated with peri-implantitis.
PMID- 29340344
TI - Biomechanical Comparison of Different Implant Inclinations and Cantilever Lengths
in All-on-4 Treatment Concept by Three-Dimensional Finite Element Analysis.
AB - PURPOSE: The aim of this study was to evaluate the effect of implant inclination
and cantilever length on the stress distribution in mandibular cortical bone,
implant, abutment, prosthetic framework, and prosthetic screw via three
dimensional (3D) finite element analysis (FEA). MATERIALS AND METHODS: Four
different finite element models (0-0, 17-17, 30-30, 45-30) were designed
according to the tilting angle (0, 17, 30, and 45 degrees) of the posterior
implant and angle of multiunit abutments (0, 17, and 30 degrees). Screw-retained
fixed prostheses with different cantilever lengths in accordance with implant
inclination were modeled. A foodstuff was used for the 100-N load application.
Maximum principal (Pmax) and minimum principal (Pmin) stresses were calculated
for cortical bone, and von Mises stress values were calculated for the implant,
abutment, metal framework, and prosthetic screw. RESULTS: The highest stress
values were observed in the anterior implant, surrounding bone, and prosthetic
components of the 0-0 configuration. Pmin stress values in bone were gradually
decreased with the increasing inclination of both anterior and posterior
implants. Peak Pmax stress values were detected in the 0-0 group. For the
cortical bone around the posterior implant, the 30-30 group showed the lowest
Pmax value. The highest von Mises stress on implants was found at the posterior
implant of the 30-30 group. The stress values on abutments gradually decreased
with the increase of the angulation of the posterior implants. For prosthetic
screws, the 30-30 and 45-30 groups exhibited lower stress values, and for the
metal framework, the 30-30 group exhibited lower stress values. CONCLUSION:
Biomechanical comparison via 3D FEA revealed that decreasing the cantilever
length by tilting the posterior implants resulted in a reduction in stress values
in the peri-implant bone, abutment, prosthetic screw, and metal framework. The
groups with 30- and 45-degree tilted posterior implants and shorter cantilever
lengths showed better stress distributions in comparison to the straight and 17
degree tilted groups.
PMID- 29340345
TI - Intraosseous Temperature Changes During Implant Site Preparation: In Vitro
Comparison of Thermocouples and Infrared Thermography.
AB - PURPOSE: Implant-supported dental prostheses are based on the principle of
osseointegration, and the success of dental implantation depends on adequate
formation of this intimate bone-to-implant contact. The application of heat
during the drilling procedure leads to a rise in intraosseous temperature at the
prospective implant site, which may result in various complications. The purpose
of the present study was to compare the ability of thermocouples and infrared
thermography to detect changes in intraosseous temperature during dental implant
site preparation. MATERIALS AND METHODS: Standardized bovine costae bone blocks
were used to simulate the cortical bone of the human mandible. Steel implant form
drills with a diameter of 3.0 mm were used. Two types of irrigation systems were
used (external cooling only and combined internal and external cooling). Drilling
was performed at a constant speed (1,200 rpm). Changes in intraosseous
temperature were evaluated using Type T Cu-CuNi thermocouples and an infrared
thermography camera system at contact pressures of 5 and 20 N. RESULTS: Infrared
thermography detected significantly greater increases in intraosseous temperature
(DeltaT) than thermocouples for all tested combinations of cooling system and
contact pressure (P <= .0001). CONCLUSION: These results suggest that
thermography more accurately reflects intraosseous temperature changes during
implant site preparation than thermocouples.
PMID- 29340346
TI - Effects of Local Drug and Chemical Compound Delivery on Bone Regeneration Around
Dental Implants in Animal Models: A Systematic Review and Meta-Analysis.
AB - PURPOSE: One of the suggested methods for enhancing osseointegration is the local
application of drug agents around implant surfaces. The aim of this review was to
evaluate the methods most commonly used for local drug and chemical compound
delivery to implant sites and assess their influence on osseointegration.
MATERIALS AND METHODS: An electronic search was undertaken in three databases
(PubMed, Scopus, Embase). The search was limited to animal experiments using
endosseous implants combined with local drug delivery systems. Meta-analyses were
performed for the outcome bone-to-implant contact (BIC). RESULTS: Sixty-one
studies met the inclusion criteria. Calcium phosphate (CaP), bisphosphonates
(BPs), and bone morphogenetic proteins (BMPs) were the most commonly used
chemical compounds. There were two main methods for local drug delivery at the
bone-implant interface: (1) directly from an implant surface by coating or
immobilizing techniques, and (2) the local application of drugs to the implant
site, using carriers. There was a statistically significant increase in BIC for
both local drug delivery methods (P = .02 and P < .0001, respectively) compared
with the control methods. There was a statistically significant increase in BIC
when CaP (P = .0001) and BMPs (P = .02) were either coating implants or were
delivered to the implant site, in comparison to when drugs were not used. The
difference was not significant for the use of BPs (P = .15). CONCLUSION: It is
suggested that the use of local chemical compound delivery systems around
implants could significantly improve implant osseointegration in animal models.
It is a matter of debate whether these in vivo results might have some
significant effect in the human clinical setting in the long term.
PMID- 29340347
TI - Effect of Attachment Type on Denture Strain in Maxillary Implant Overdentures:
Part 2. Palateless Overdentures.
AB - PURPOSE: The aim of this study was to examine the deformation modality of
palateless maxillary implant overdentures using isolated attachments under
various implant configurations. MATERIALS AND METHODS: A maxillary edentulous
model with implants inserted in the anterior, premolar, and molar areas was
fabricated, and three types of unsplinted attachments-ball, locator, and magnet
were set on the implants distributed in various configurations. Experimental
palateless dentures were fabricated, and two strain gauges were attached at the
anterior midline of the labial and palatal sides. A vertical occlusal load of 98
N was applied, and the shear strains of dentures were measured. The measurements
of strains were compared with the Kruskal-Wallis test (P = .05). RESULTS: The
strains of the labial side were much larger than those of the palatal side except
for those using the ball attachment. The strains using the magnet attachment on
anterior implants were significantly larger than those using other attachments (P
< .05). Those using anterior implants were significantly smaller than those using
premolar or molar implants (P < .05). CONCLUSION: The strains of palateless
overdentures were different according to the attachments and implant
distribution. However, when using molar implants, there was no significant
difference among the three attachments.
PMID- 29340348
TI - Peri-implant Tissues and Patient Satisfaction After Treatment of Vertically
Augmented Atrophic Posterior Mandibles with Intraoral Onlay Block Bone Grafts: A
Retrospective 3-Year Case Series Follow-up Study.
AB - PURPOSE: To evaluate the peri-implant soft and hard tissues of dental implants
placed in vertically regenerated posterior mandibles with intraoral onlay block
bone grafts and patient satisfaction at 3-year follow-up. MATERIALS AND METHODS:
A retrospective study of patients with dental implants placed in posterior
mandibular sites vertically augmented with intraoral onlay block bone grafts was
carried out between 2005 and 2009 at the University of Valencia. The outcomes
assessed at the 3-year follow-up visit were the peri-implant soft tissues (Plaque
Index and Bleeding Index, probing depth, keratinized mucosa width, and
recession), implant survival and success rates, marginal bone loss, and patient
satisfaction. RESULTS: Sixteen patients with 36 implants were included. The mean
Plaque Index and Bleeding Index scores were <= 0.4. The mean band of facial
keratinized mucosa was >= 3 mm in 52.7% of implants; 38.8% of the implants showed
facial recession. The mean midfacial recession was -0.31 +/- 0.75 mm. Implant
survival reached 100%, while the success rate was 85%, and the mean marginal bone
loss was 1 +/- 1.03 mm (range: 0.1 to 5.3). Good quality of life (9.19 +/- 0.40)
was reported for all patients, and the overall general satisfaction score was
8.07 +/- 1.04 (mucosa esthetics: 7.71 +/- 1.45; prosthesis esthetics: 8.42 +/-
0.6; chewing: 8.68 +/- 0.94; ease of cleaning: 8.01 +/- 1.03). CONCLUSION:
Considering the limitations of the study, implants in vertically augmented
posterior mandibular areas with intraoral onlay block bone grafts showed good
soft tissue levels and high patient satisfaction. No implants were lost at 3
years postloading, though one-fifth of the patients showed a statistically
significant marginal bone loss.
PMID- 29340349
TI - Prevalence of Dental Implants and Evaluation of Peri-implant Bone Levels in
Patients Presenting to a Dental School: A Radiographic Cross-Sectional 2-Year
Study.
AB - PURPOSE: To evaluate the number of patients with dental implants who present to a
dental school clinic for screening and to report the prevalence of peri-implant
bone level change detected on digital panoramic radiographs of those subjects.
MATERIALS AND METHODS: Patient screening files for 9,422 patients over a 2-year
period were examined to see how many patients presented with dental implants.
Those patients with at least one implant were further evaluated by measuring the
bone level on the mesial and distal sides of the implant using the screening
radiograph. RESULTS: A total of 187 patients (2%) had at least one implant. In
regard to implants, 423 were examined and 146 (33%) had no detectable bone loss
defined as bone level below the top of the implant. When thresholds of bone loss
were evaluated, 109 implants (25%) had >= 2 mm of bone loss on either the mesial
or distal sides or both. The median bone loss was 1.74 mm for the 277 implants
with detectable bone loss and 2.97 mm for the 109 implants that had >= 2 mm bone
loss. Interestingly, patients who were >= 70 years of age had significantly (P =
.03) more bone loss in the mandible compared with the maxilla, while patients who
were 60 to 69 years of age had significantly greater loss in the maxilla.
CONCLUSION: These data reveal that for patients presenting to the dental school
for a screening over a 2-year period, 1.98% had one or more dental implants.
Furthermore, those patients with implants had a minimum amount of bone loss as
measured from the top of the implant.
PMID- 29340350
TI - Estimating the Importance of Significant Risk Factors for Early Dental Implant
Failure: A Monte Carlo Simulation.
AB - PURPOSE: The purpose of this study was to develop a probabilistic estimation of
the strength of risk factors associated with early dental implant failure and
rank them by importance. MATERIALS AND METHODS: A systematic literature search
was performed on PubMed, Web of Knowledge, Scopus, Cochrane Central Register of
Controlled Trials, and grey literature up to April 2017. A total of 368 records
were identified. Following the removal of duplicate and irrelevant records, 56
were screened. Eight studies met the inclusion criteria, in which seven
statistically significant risk factors for early failure were selected and used
to build a conceptual simulation model. Selected risk factors were, namely, "male
sex," "smoking," "bone quality," "short implants," "wide implants," "adjacent
teeth," and "periodontitis." Monte Carlo simulation with 100,000 iterations and a
sensitivity analysis were performed to evaluate the risk estimates of these risk
factors and to identify which of the risk factors are more important in
influencing the model, respectively. RESULTS: The performed simulation model has
shown a significant difference in terms of estimated effects of the risk factors
on early failure rate. As a result, the most sensitive risk factor was found to
be "periodontitis" with the second being "adjacent teeth" and the third
"smoking." The least sensitive factor for early failure was "wide implants."
CONCLUSION: This study develops a better understanding of the importance of risk
factors for early dental implant failure by an estimated ranking.
PMID- 29340351
TI - Effect of Low-Level Laser on the Healing of Bone Defects Filled with Autogenous
Bone or Bioactive Glass: In Vivo Study.
AB - PURPOSE: This study evaluated the effect of low-level laser therapy (LLLT) on the
healing of bone defects filled with autogenous bone or bioactive glass. MATERIALS
AND METHODS: A critical size defect with 5-mm diameter was created on the
calvaria of 60 adult male rats divided into 6 groups (n = 10): group C (control),
group LLLT (LLLT - GaAlAs, wavelength of 780 nm, power of 100 mW, energy density
of 210 J/cm2 per point during 60 seconds/point, in five points, only once, after
creation of the surgical defect), group AB (autogenous bone), group AB+LLLT
(autogenous bone + LLLT), group BG (bioactive glass), group BG+LLLT (bioactive
glass + LLLT). All animals were sacrificed at 30 days after surgery. The areas of
newly formed bone (ANFB) and areas of remaining particles (ARP) were calculated
in relation to the total area (TA). RESULTS: The highest mean +/- SD ANFB was
observed for group LLLT (47.67% +/- 8.66%), followed by groups AB+LLLT (30.98% +/
16.59%) and BG+LLLT (31.13% +/- 16.98%). There was a statistically significant
difference in relation to ANFB between group C and the other groups, except for
comparison with group BG (Tukey test, P > .05). There was no statistically
significant difference in ANFB values between group AB and the other study groups
(Tukey test, P > .05), group AB+LLLT and groups BG and BG+LLLT (Tukey test, P >
.05), and between groups BG and BG+LLLT (Tukey test, P > .05). The highest mean
+/- SD ARP was found for group BG (25.15% +/- 4.82%), followed by group BG+LLLT
(17.06% +/- 9.01%), and there was no significant difference between groups (t
test, P > .05). CONCLUSION: The LLLT, in the present application protocol, did
not increase the area of new bone formation when associated with autogenous bone
or bioactive glass.
PMID- 29340352
TI - Bone Healing at Functionally Loaded and Unloaded Screw-Shaped Implants Supporting
Single Crowns: A Histomorphometric Study in Humans.
AB - PURPOSE: To evaluate histologically and histomorphometrically the effect of a
delayed load on healing at implants with a moderately rough surface. MATERIALS
AND METHODS: Two solid titanium screw-shaped devices, 5 mm long and 3.5 mm in
diameter, were inserted in the distal segments of the alveolar ridge of 16
volunteer patients in a nonsubmerged fashion. After 2 months, one implant was
loaded, while the other was left unloaded. After 2 months, the two implants were
collected from 10 patients using a sonic instrument, and ground sections were
prepared from the biopsy specimens. Histomorphometric analyses were performed.
RESULTS: After 4 months of healing, biopsy specimens from 10 patients were
available for analyses (n = 10). The total bone-to-implant contact percentage was
86.8% +/- 6.5% and 84.6% +/- 3.7% for loaded and unloaded implants, respectively.
New bone was represented by 85.5% +/- 6.7% and 83.4% +/- 3.9% at the loaded and
unloaded sites, respectively. A very small amount of old parent bone was found.
The density of the mineralized bone was 76.8% +/- 8.3% for the loaded sites and
74.1% +/- 10.5% for the unloaded sites. The percentages of new and old bone
densities were 69.0% +/- 8.3% and 7.8% +/- 3.9% at the loaded sites, and 65.9% +/
10.3% and 8.2% +/- 4.5% at the unloaded sites, respectively. No statistically
significant differences were disclosed. CONCLUSION: Applying a delayed load to
implants supporting single crowns did not yield statistically significant
differences, and only a tendency of higher osseointegration and bone density was
observed at loaded sites compared with the unloaded sites.
PMID- 29340353
TI - Clinical Performance of One-Piece, Screw-Retained Implant Crowns Based on Hand
Veneered CAD/CAM Zirconia Abutments After a Mean Follow-up Period of 2.3 Years.
AB - PURPOSE: The aim of this study was to evaluate the clinical performance of one
piece, screw-retained implant crowns based on hand-veneered computer-aided
design/computer-aided manufacture (CAD/CAM) zirconium dioxide abutments with a
crossfit connection at least 1 year after insertion of the crown. MATERIALS AND
METHODS: Consecutive patients who had received at least one Straumann bone level
implant and one-piece, screw-retained implant crowns fabricated with CARES
zirconium dioxide abutments were reexamined. Patient satisfaction, occlusal and
peri-implant parameters, mechanical and biologic complications, radiologic
parameters, and esthetics were recorded. RESULTS: A total of 50 implant crowns in
the anterior and premolar region were examined in 41 patients. The follow-up
period of the definitive reconstructions ranged from 1.1 to 3.8 years. No
technical and no biologic complications had occurred. At the reexamination, 100%
of the implants and reconstructions were in situ. Radiographic evaluation
revealed a mean distance from the implant shoulder to the first visible bone-to
implant contact of 0.06 mm at the follow-up examination. CONCLUSION: Screw
retained crowns based on veneered CAD/CAM zirconium dioxide abutments with a
crossfit connection seem to be a promising way to replace missing teeth in the
anterior and premolar region. In the short term, neither failures of components
nor complications were noted, and the clinical and radiographic data revealed
stable hard and soft tissue conditions.
PMID- 29340354
TI - Implant Mandibular Overdentures Retained by Immediately Loaded Implants: A 1-Year
Randomized Trial Comparing Patient-Based Outcomes Between Mini Dental Implants
and Standard-Sized Implants.
AB - PURPOSE: The aim of this 1-year randomized trial was to determine the stability
and the magnitude of the effect of converting patients' conventional mandibular
dentures to implant overdentures (IODs) on their satisfaction and oral health
related quality of life (OHRQoL). The IODs were retained either with two
immediately loaded interconnected standard-diameter implants or with four
immediately loaded mini dental implants (MDIs). MATERIALS AND METHODS: Fifty
completely edentulous subjects complaining about insufficient retention of their
mandibular dentures were randomly assigned to two groups; 25 patients received
IODs retained with four MDIs and 25 patients received IODs retained with two
standard-sized tissue level (STL) interconnected implants. All IODs were opposed
by conventional maxillary dentures. Patients rated their satisfaction on a 100-mm
visual analog scale (VAS) and their quality of life on a denture-specific short
version of the oral health impact profile (OHIP-20) before assignment, and after
3 and 12 months. A two-way mixed analysis of variance (ANOVA) was conducted to
assess the change in time and its interaction with treatment mode on patients'
overall satisfaction ratings, the total OHIP-20, and their specific domain
scores. RESULTS: Immediate loading was possible for all the patients who received
the MDIs. By contrast, the immediate loading protocol could be followed for only
15 of the patients allocated to the STL implant group. For the remaining
patients, a delayed loading protocol was applied. There was a significant
improvement in patients' general satisfaction between baseline and 3 months and
between baseline and 12 months postoperatively (F2,44 = 81.006, P < .001). This
increase did not differ between the treatment groups (F4,90 = 1.838, P = .128).
The results also showed a decrease in mean overall OHIP score (F2,43 = 46.863, P
< .001) between baseline and 3 months and between baseline and 12 months
postoperatively, indicating a higher level of OHRQoL. In addition, patients
scored lower 3 and 12 months after treatment than at baseline for all seven
domains. This decrease did not differ between the treatment groups (F4,88 =
0.608, P = .658). CONCLUSION: The results suggested that in terms of patient
based outcomes, mandibular overdentures retained by immediately loaded MDIs can
offer an improvement of equal magnitude with that achieved by overdentures
retained by standard-sized implants.
PMID- 29340355
TI - Human Histologic Evidence of New Bone Formation and Osseointegration Between Root
Dentin (Unplanned Socket-Shield) and Dental Implant: Case Report.
AB - The socket-shield technique described 7 years ago has since grown in its
reporting in the literature as a valid method of ridge preservation at immediate
implant placement. To date, large clinical cohorts with up-to-4-year follow-up
have been reported. Additionally, evidence of tissue histology at the dental
implant and socket-shield has been demonstrated in the animal model. However,
human histologic evidence has not yet been available, and the clinician's
uncertainty regarding the tissues that may form between the socket-shield and
dental implant may remain unanswered until now. This case report presents the
first human histologic evidence that bone may entirely fill the space between
root dentin and an osseointegrated implant surface.
PMID- 29340356
TI - Long-life sodium/carbon fluoride batteries with flexible, binder-free fluorinated
mesocarbon microbead film electrodes.
AB - Home-made fluorinated mesocarbon microbeads (F-MCMBs) were synthesised and
employed in sodium batteries. Flexible, binder-free F-MCMB film electrodes were
fabricated to enhance the cycle stability, and 65 cycles were achieved, which is
the longest lifespan reported thus far. Nitrogen-doped graphene nanosheets (N
GNS) were also introduced as a catalyst, with the aim of lowering the voltage
gap.
PMID- 29340357
TI - Expanding the chemical diversity of TNA with tUTP derivatives that are substrates
for a TNA polymerase.
AB - Expanding the chemical diversity of threose nucleic acid (TNA) beyond the natural
bases would enable the development of TNA polymers with enhanced physicochemical
properties. Here, we describe a versatile approach for increasing the chemical
diversity of TNA using 5-alkynyl-modified alpha-l-threofuranosyl uridine
triphosphates that are substrates for a TNA polymerase.
PMID- 29340358
TI - A strategy for generating aryl radicals from arylborates through organic
photoredox catalysis: photo-Meerwein type arylation of electron-deficient
alkenes.
AB - Photoinduced reactions of arylboronic acids with electron deficient alkenes under
mild organic photoredox catalysis conditions lead to the formation of Meerwein
arylation type adducts via the generation of aryl radicals.
PMID- 29340359
TI - [UCl4(HCN)4] - a hydrogen cyanide complex of uranium tetrachloride.
AB - The reaction of uranium tetrachloride with anhydrous liquid hydrogen cyanide
yields a turquoise microcrystalline powder of
tetrachloridotetraformonitrileuranium(iv), [UCl4(HCN)4]. We determined the
crystal structure of this compound by powder neutron diffraction. The compound
was further characterized by IR spectroscopy and thermogravimetric analysis as
well as by magnetic measurements. The paramagnetic compound crystallizes in the
tetragonal space group type I4[combining macron]. To the best of our knowledge
this compound represents the first structurally elucidated uranium(iv) complex
with HCN as a ligand.
PMID- 29340360
TI - Saline hybrid nanoparticles with phthalocyanine and tetraphenylporphine anions
showing efficient singlet-oxygen production and photocatalysis.
AB - The inorganic-organic hybrid nanoparticles Gd43+[AlPCS4]34- and La43+[TPPS4]34-
([AlPCS4]4-: aluminium(iii) chlorido phthalocyanine tetrasulfonate; [TPPS4]4-:
tetraphenylporphine sulfonate) are shown for the first time. Both were obtained
via aqueous synthesis and contain extremely high contents of [AlPCS4]34- (81 wt%)
and [TPPS4]34- (83 wt%). They show efficient singlet oxygen (1O2) production upon
daylight and red-light irradiation. Photocatalysis is evidenced via dye
degradation as a proof-of-the-concept and proceeds with daylight and even red
light illumination.
PMID- 29340362
TI - Synergetic topography and chemistry cues guiding osteogenic differentiation in
bone marrow stromal cells through ERK1/2 and p38 MAPK signaling pathway.
AB - Both the topographic surface and chemical composition modification can enhance
rapid osteogenic differentiation and bone formation. Till now, the synergetic
effects of topography and chemistry cues guiding biological responses have been
rarely reported. Herein, the ordered micro-patterned topography and classically
essential trace element of strontium (Sr) ion doping were selected to imitate
topography and chemistry cues, respectively. The ordered micro-patterned
topography on Sr ion-doped bioceramics was successfully duplicated using the
nylon sieve as the template. Biological response results revealed that the micro
patterned topography design or Sr doping could promote cell attachment, ALP
activity, and osteogenic differentiation of bone marrow-derived mesenchymal stem
cells (BMSCs). Most importantly, the samples both with micro-patterned topography
and Sr doping showed the highest promotion effects, and could synergistically
activate the ERK1/2 and p38 MAPK signaling pathways. The results suggested that
the grafts with both specific topography and chemistry cues have synergetic
effects on osteogenic activity of BMSCs and provide an effective approach to
design functional bone grafts and cell culture substrates.
PMID- 29340361
TI - A curcumin-loaded polymeric micelle as a carrier of a microRNA-21 antisense
oligonucleotide for enhanced anti-tumor effects in a glioblastoma animal model.
AB - A glioblastoma is a common primary brain tumor that expresses microRNA-21 (miR
21), which inhibits the expression of pro-apoptotic genes such as phosphatase and
tensin homologue (PTEN) and programmed cell death 4 (PDCD4). Therefore, an
antisense-oligonucleotide against miR-21 (miR21ASO) could have therapeutic
effects for glioblastomas. In this study, curcumin was loaded into deoxycholic
acid-conjugated polyethylenimine (DP) micelles. The curcumin-loaded DP micelle
(DP-Cur) was evaluated as a carrier for the combined delivery of curcumin and
miR21ASO. Gel retardation and heparin competition assays showed that DP-Cur
formed stable complexes with miR21ASO. The anti-tumor effects of the combined
delivery of curcumin and miR21ASO were evaluated in C6 glioblastoma cells. In
vitro transfection showed that DP-Cur had an miR21ASO delivery efficiency similar
to that of polyethylenimine (25 kDa, PEI25k) and DP. In the C6 cells, the
delivery of miR21ASO using DP-Cur effectively reduced the miR21 level. The
miR21ASO/DP-Cur complex induced apoptosis more effectively than the single
delivery of curcumin or miR21ASO. The therapeutic effect of the miR21ASO/DP-Cur
complex was also evaluated in an intracranial glioblastoma animal model. The
miR21ASO/DP-Cur complex reduced the tumor volume more effectively than single
therapy of curcumin or miR21ASO. Immunohistochemistry showed that PDCD4 and PTEN
were induced in the miR21ASO/DP and miR21ASO/DP-Cur complex groups. Therefore, DP
Cur is an efficient carrier of miR21ASO and the combined delivery of miR21ASO and
curcumin may be useful in the development of combination therapy for
glioblastoma.
PMID- 29340363
TI - Central-metal effect on intramolecular vibrational energy transfer of M(CO)5Br (M
= Mn, Re) probed by two-dimensional infrared spectroscopy.
AB - Vibrational energy transfer in transition metal complexes with flexible
structures in condensed phases is of central importance to catalytical chemistry
processes. In this work, two molecules with different metal atoms, M(CO)5Br
(where M = Mn, Re), were used as model systems, and their axial and radial
carbonyl stretching modes as infrared probes. The central-metal effect on
intramolecular vibrational energy redistribution (IVR) in M(CO)5Br was
investigated in polar and nonpolar solvents. The linear infrared (IR) peak
splitting between carbonyl vibrations increases as the metal atom changes from Mn
to Re. The waiting-time dependent two-dimensional infrared diagonal- and off
diagonal peak amplitudes reveal a faster IVR process in Re(CO)5Br than in
Mn(CO)5Br. With the aid of density functional theory (DFT) calculations, the
central-metal effect on IVR time linearly correlates with the vibrational
coupling strength between the two involved modes. In addition, the polar solvent
is found to accelerate the IVR process by affecting the anharmonic vibrational
potentials of a solute vibration mode.
PMID- 29340374
TI - A well-defined unimolecular channel facilitates chloride transport.
AB - A unimolecular ion channel was optimized by functionalization with a new type of
rigid-rod oligomer. The macrocycle pendant endows chloride selectivity and the
fluorescence feature and suitable length of the rod facilitates the visual
insertion of channels into the lipid bilayer, resulting in efficient ion
transport with an EC50 value of 0.36 MUM.
PMID- 29340375
TI - Enhancement of BMP-2-mediated angiogenesis and osteogenesis by 2-N,6-O-sulfated
chitosan in bone regeneration.
AB - Sulfated polysaccharides are attractive semi-synthesized materials that can be
used as a mimic of heparan sulfate to modulate the protein activity and other
physiological processes. In this study, we employed sulfated chitosan to enhance
the angiogenic capacity of bone morphogenic protein-2 (BMP-2). Bone marrow
stromal cells (BMSCs) cultured in a combination of BMP-2 and 2-N,6-O-sulfated
chitosan (SCS) group exhibited a higher cell viability and sprouting ability. The
cells also secreted more VEGF and NO. The expression patterns of angiogenic and
osteogenic genes were analyzed, and VEGFR2 signaling was found to play a role in
the enhancing effect of SCS. The chick embryo chorioallantoic membrane (CAM)
assay revealed an enhanced angiogenic effect of BMP-2 when SCS was involved. In
addition, we investigated angiogenesis and osteogenesis in mouse using a BMP-2
induced ectopic bone model. Histological and immune-staining analysis revealed
that both bone and vascular tissue were enhanced when SCS was added. These data
prove that SCS can improve the angiogenic potential of BMP-2 and thus lead to
better bone regeneration.
PMID- 29340376
TI - The second-harmonic generation intensification derived from localization
conjugated pi-orbitals in O22.
AB - Molecular construction with pi-conjugated groups is a favorable strategy to
discover superior nonlinear optical (NLO) materials. Herein, a novel vanadium
carbonate compound K3[V(O2)2O]CO3 (KVCO), which combines two different pi-orbital
groups, delocalized (CO3)2- pi-orbital groups and localized (O2)2- pi-orbital
groups, was synthesized. Benefiting from the well-arranged [V(O2)2OCO3] unit and
dual-synergistic pi-d-pi interaction, KVCO has the largest second harmonic
generation (SHG) effect (about 20 times that of KDP) among the current carbonate
NLO materials. Moreover, first-principles calculation elucidated the coupling
enhancement mechanism between (CO3)2-, (O2)2- and VOn groups.
PMID- 29340377
TI - Metal-organic frameworks at interfaces of hybrid perovskite solar cells for
enhanced photovoltaic properties.
AB - In this study, metal-organic frameworks, as an interfacial layer, were introduced
into perovskite solar cells (PSCs) for the first time. An interface modified with
the metal-organic framework ZIF-8 efficiently enhanced perovskite crystallinity
and grain sizes, and the photovoltaic performance of the PSCs was significantly
improved, resulting in a maximum PCE of 16.99%.
PMID- 29340378
TI - Chemical dynamics simulations of CID of peptide ions: comparisons between
TIK(H+)2 and TLK(H+)2 fragmentation dynamics, and with thermal simulations.
AB - Gas phase unimolecular fragmentation of the two model doubly protonated
tripeptides threonine-isoleucine-lysine (TIK) and threonine-leucine-lysine (TLK)
is studied using chemical dynamics simulations. Attention is focused on different
aspects of collision induced dissociation (CID): fragmentation pathways, energy
transfer, theoretical mass spectra, fragmentation mechanisms, and the possibility
of distinguishing isoleucine (I) and leucine (L). Furthermore, discussion is
given regarding the differences between single collision CID activation, which
results from a localized impact between the ions and a colliding molecule N2, and
previous thermal activation simulation results; Z. Homayoon, S. Pratihar, E.
Dratz, R. Snider, R. Spezia, G. L. Barnes, V. Macaluso, A. Martin-Somer and W. L.
Hase, J. Phys. Chem. A, 2016, 120, 8211-8227. Upon thermal activation
unimolecular fragmentation is statistical and in accord with RRKM unimolecular
rate theory. Simulations show that in collisional activation some non-statistical
fragmentation occurs, including shattering, which is not present when the ions
dissociate statistically. Products formed by non-statistical shattering
mechanisms may be related to characteristic mass spectrometry peaks which
distinguish the two isomers I and L.
PMID- 29340379
TI - Enhanced photocatalytic efficiency of C3N4/BiFeO3 heterojunctions: the
synergistic effects of band alignment and ferroelectricity.
AB - As one of the most promising photocatalysts, graphitic carbon nitride (g-C3N4)
shows a visible light response and great chemical stability. However, its
relatively low photocatalytic efficiency is a major obstacle to actual
applications. Here an effective and feasible method to dramatically increase the
visible light photocatalytic efficiency by forming C3N4/BiFeO3 ferroelectric
heterojunctions is reported, wherein the band alignment and piezo
/ferroelectricity have synergistic positive effects in accelerating the
separation of the photogenerated carriers. At the optimum composition of 10 wt%
BiFeO3, the heterojunction shows 1.4 times improved photocatalytic efficiency
than that of the pure C3N4. Most importantly, mechanical pressing and electrical
poling can also improve the photocatalytic efficiencies by 1.3 times and 1.8
times, respectively. The optimized photocatalytic efficiency is even comparable
with that of some noble metal based compounds. These results not only prove the
improved photocatalytic activity of the C3N4-ferroelectric heterojunctions, but
also provide a new approach for designing high-performance photocatalysts by
taking advantage of ferroelectricity.
PMID- 29340380
TI - A DFT study of the adsorption of short peptides on Mg and Mg-based alloy
surfaces.
AB - Adsorption of short peptides, including three dipeptides: arginine-glycine (Arg
Gly), glycine-aspartic acid (Gly-Asp), arginine-aspartic acid (Arg-Asp), and one
tripeptide arginine-glycine-aspartic acid (RGD), on the surfaces of Mg and Mg
alloys (Mg-Zn, Mg-Y, and Mg-Nd), was studied using the first-principles
calculations based on density functional theory (DFT), considering van der Waals
(vdW) correction. The calculated adsorption energies (Eads) of short peptides on
the clean Mg(0001) surface are in the range of -1.73 to -2.80 eV per dipeptide,
and -3.24 eV for RGD. The short peptides prefer to bond to Mg atoms at the
surface by the O and N anions in their functional groups. For the clean Mg(0001)
surface, the Eads of the short peptides are exclusively dominated by the number
of functional groups binding to the surface. However, for the surface of the Mg
Zn alloy (1% Zn), the adsorption of the peptides is clearly enhanced (by about
0.3 eV per peptide) due to the enhanced N-Mg bond and the electrostatic
interactions between the doped Zn at the surface and the backbone chains of the
peptides. Furthermore, the attractive interactions are increased with the
increase of doped Zn contents (up to 3%). In contrast, for the surfaces of Mg-Y
(1% Y) and Mg-Nd (1% Nd) alloys, the adsorption of the peptides is slightly
weakened compared to that on the clean Mg(0001) surfaces. Our results provide
useful guidance in understanding the interactions between peptides and the Mg
based biomedical alloy surfaces at the atomic scale in the biomimetic coating
fields.
PMID- 29340381
TI - Unraveling the mystery of "tech red" - a volatile technetium oxide.
AB - We show that a Tc2O5 molecular species is the likely identity of an unknown
volatile oxide which has remained uncharacterized for 50+ years. Exploration of
this molecule's absorption spectra and intermolecular self-interactions provides
a close match to experimental data and an explanation for volatility and
resistance to crystallization.
PMID- 29340382
TI - Tuning the indirect-direct band gap transition in the MoS2-xSex armchair nanotube
by diameter modulation.
AB - The application of the reported armchair transition-metal dichalcogenide (MoS2,
MoTe2, MoSTe and WS2, etc.) nanotube is hindered for the optoelectronic devices
due to the indirect band gap. By using first-principles calculations, the
electronic structures of MoS2-xSex single-wall armchair nanotubes with respect to
different diameters are investigated. The MoS2 armchair nanotube exhibits an
indirect band gap as a function of nanotube diameters from 10 A to 50 A, whereas
MoSSe and MoSe2 exhibit a surprising diameter-induced indirect-direct band gap
crossover at the diameters of 25 A and 33 A, respectively. We also find that the
optical properties of MoS2-xSex armchair nanotubes are anisotropic and strongly
depend on the diameter.
PMID- 29340383
TI - Alamethicin self-assembling in lipid membranes: concentration dependence from
pulsed EPR of spin labels.
AB - The antimicrobial action of the peptide antibiotic alamethicin (Alm) is commonly
related to peptide self-assembling resulting in the formation of voltage
dependent channels in bacterial membranes, which induces ion permeation. To
obtain a deeper insight into the mechanism of channel formation, it is useful to
know the dependence of self-assembling on peptide concentration. With this aim,
we studied Alm F50/5 spin-labeled analogs in a model 1-palmitoyl-2-oleoyl-sn
glycero-3-phosphocholine (POPC) membrane, for peptide-to-lipid (P/L) ratios
varying between 1/1500 and 1/100. Pulsed electron-electron double resonance
(PELDOR) spectroscopy reveals that even at the lowest concentration investigated,
the Alm molecules assemble into dimers. Moreover, under these conditions,
electron spin echo envelope modulation (ESEEM) spectroscopy of D2O-hydrated
membranes shows an abrupt change from the in-plane to the trans-membrane
orientation of the peptide. Therefore, we hypothesize that dimer formation and
peptide reorientation are concurrent processes and represent the initial step of
peptide self-assembling. By increasing peptide concentration, higher oligomers
are formed. A simple kinetic model of equilibrium among monomers, dimers, and
pentamers allows for satisfactorily describing the experimental PELDOR data. The
inter-label distances in the oligomers obtained from PELDOR experiments become
better resolved with increasing P/L ratio, thus suggesting that the
supramolecular organization of the higher-order oligomers becomes more defined.
PMID- 29340384
TI - Kinetics of the a-C3H5 + O2 reaction, investigated by photoionization using
synchrotron radiation.
AB - The kinetics of the combustion-relevant reaction of the allyl radical, a-C3H5,
with molecular oxygen has been studied in a flow tube reactor at the vacuum
ultraviolet (VUV) beamline of the Swiss Light Source storage ring, using the CRF
PEPICO (Combustion Reactions Followed by Photoelectron Photoion Coincidence
Spectroscopy) setup. The ability to measure threshold photoelectron spectra
enables a background-free detection of reactive species as well as an isomer
specific analysis of reaction products. Allyl was generated by direct
photodissociation of allyl iodide at 266 nm and 213 nm and indirectly by the
reaction of propene with Cl atoms, which were generated by photolysis from oxalyl
chloride at 266 nm. Experiments were conducted at room temperature at low
pressures between 0.8 and 3 mbar using Ar as the buffer gas and with excess O2 to
maintain nearly pseudo-first-order reaction conditions. Whereas allyl was
detected by photoionisation using synchrotron radiation, the main reaction
product allyl peroxy was not observed due to dissociative ionisation of this
weakly bound species. From the concentration-time profiles of the allyl signal,
second-order rate constants between 1.35 * 1011 cm3 mol-1 s-1 at 0.8 mbar and
1.75 * 1011 cm3 mol-1 s-1 at 3 mbar were determined. The rates obtained for the
different allyl radical generation schemes agree well with each other, but are
about a factor of 2 higher than the ones reported previously using He as a buffer
gas. The discrepancy is partly attributed to the higher collision efficiency of
Ar causing a varying fall-off behavior. When allyl is produced by the reaction of
propene with Cl atom, an unexpected product is observed at m/z = 68, which was
identified as 1,3-butadienal in the threshold photoelectron spectrum. It is
formed in a secondary reaction of allyl with the OCCl radical, which is generated
in the 266 nm photolysis of oxalyl chloride.
PMID- 29340385
TI - Coordination supramolecular assemblies of a monohydroxycucurbit[7]uril and their
potential applications in gas sorption.
AB - Coordination supramolecular assemblies of monohydroxycucurbit[7]uril ((HO)Q[7])
with alkaline earth metal ions (AE2+) have been formed in aqueous HCl solution in
the presence of tetrachloride cadmium anions ([CdCl4]2-) as a structure directing
agent. The driving force for the assembly could be attributed to the interaction
of the positive electro-potential outer-surface of (HO)Q[7] molecules with
[CdCl4]2- anions and ionic dipole interaction of the hydroxyl of (HO)Q[7]
molecules with [CdCl4]2- anions. Moreover, the porous structure of the
(HO)Q[7]/AE2+-based coordination supramolecular assemblies could result in
potential applications in the selective sorption of polar volatile organic
molecules, which may be useful in molecular sieves, sensors, absorption and
separation.
PMID- 29340387
TI - Pb3(SeO3)Br4: a new nonlinear optical material with enhanced SHG response
designed via an ion-substitution strategy.
AB - Using an ion-substitution strategy, herein, a new polar material, Pb3(SeO3)Br4,
with a greatly enhanced SHG response has been successfully designed and
synthesized through a hydrothermal reaction. Pb3(SeO3)Br4 crystallizes in the NCS
space group P212121 and consists of a three-dimensional framework formed by
interconnecting one-dimensional chains, with a good thermal stability up to 230
degrees C. This compound exhibits a phase-matchable SHG response as strong as
that of KH2PO4 (KDP) and a relatively wide mid-infrared (mid-IR) transparent
window. Moreover, the optical band gap of Pb3(SeO3)Br4 reaches about 3.35 eV,
thus leading to a high laser damage threshold (LDT) of 67 MW cm-2, which is over
12 times that of AgGaS2 (<5 MW cm-2) measured under the same condition. All these
findings suggest that Pb3(SeO3)Br4 would be a candidate for an NLO material in
the mid-IR region.
PMID- 29340386
TI - On-chip functional neuroimaging with mechanical stimulation in Caenorhabditis
elegans larvae for studying development and neural circuits.
AB - Mechanosensation is fundamentally important for the abilities of an organism to
experience touch, hear sounds, and maintain balance. Caenorhabditis elegans is a
powerful system for studying mechanosensation as this worm is well suited for in
vivo functional imaging of neurons. Many years of research using labor-intensive
methods have generated a wealth of knowledge about mechanosensation in C.
elegans, and the recent microfluidic-based platforms continue to push the
boundary for this field. However, developmental aspects of sensory biology,
including mechanosensation, are still not fully understood. One current
bottleneck is the difficulty in assaying larvae because they are much smaller
than adult worms. Microfluidic devices with features small enough for larvae,
especially actuators for the delivery of mechanical stimulation, are difficult to
design and fabricate. Here, we present a series of automatic microfluidic
platforms that allow for in vivo functional imaging of C. elegans responding to
controlled mechanical stimulation at different developmental stages. Using a
novel fabrication method, we designed highly deformable pneumatically actuated on
chip structures that can deliver mechanical stimulation to larval worms. The PDMS
actuator allows for quantitatively controlled mechanical stimulation of both
gentle and harsh touch neurons, by simply changing the actuation pressure, which
makes this device easily translatable to other labs. We validated the design and
utility of our systems with studies of the functional role of mechanosensory
neurons in developing worms; we showed that gentle and harsh touch neurons
function similarly in early larvae as they do in the adult stage, which would not
have been possible previously. Finally, we investigated the effect of a sleep
like state on neuronal responses by imaging C. elegans in the lethargus state.
PMID- 29340388
TI - Recent progress of particle migration in viscoelastic fluids.
AB - Recently, research on particle migration in non-Newtonian viscoelastic fluids has
gained considerable attention. In a viscoelastic fluid, three dimensional (3D)
particle focusing can be easily realized in simple channels without the need for
any external force fields or complex microchannel structures compared with that
in a Newtonian fluid. Due to its promising properties for particle precise
focusing and manipulation, this field has been developed rapidly, and research on
the field has been shifted from fundamentals to applications. This review will
elaborate the recent progress of particle migration in viscoelastic fluids,
especially on the aspect of applications. The hydrodynamic forces on the
micro/nano particles in viscoelastic fluids are discussed. Next, we elaborate the
basic particle migration in viscoelasticity-dominant fluids and elasto-inertial
fluids in straight channels. After that, a comprehensive review on the
applications of viscoelasticity-induced particle migration (particle separation,
cell deformability measurement and alignment, particle solution exchange,
rheometry-on-a-chip and others) is presented; finally, we thrash out some
perspectives on the future directions of particle migration in viscoelastic
fluids.
PMID- 29340389
TI - The photocatalytic role of electrodeposited copper on pencil graphite.
AB - We report on the ability of template-electrodeposited copper on pencil graphite
as a novel and cost effective photocatalyst by considering the photodimerization
of p-aminothiophenol (p-ATP) to 4,4'-dimercaptoazobenzene.
PMID- 29340390
TI - Ultrafast stimulated emission of nitrophenolates in organic and aqueous
solutions.
AB - Early-time dynamics of nitroaromatics and its coressponding bases can give
valuable insights into photo-induced reactions relevant to atmospheric and
environmental processes. In this work, femtosecond broadband absorption
spectroscopy between 350 and 700 nm has been applied to explore the ultrafast
dynamics of o-, p- and m-nitrophenol anions (NP-) in basic organic and aqueous
solution. Excitation at 400 nm promotes these compounds into the first bright
electronic singlet state, which is a charge-transfer state. A surprising finding
for all nitrophenolates was a characteristic, spectrally broad stimulated
emission (SE) from the electronically excited state into the ground state. The
corresponding lifetime was on the order of a few hundred femtoseconds for o- and
p-NP- while it was roughly ten times larger for m-NP-. In line with earlier
observations, the SE is governed by an out-of-plane torsional motion of the nitro
group, leading to a close energetic approach of the relevant electronically
excited singlet and ground states. Subsequent dynamics can be assigned to excited
state absorption and ground state relaxation due to energy dissipation of the
vibrational modes to the solvent that occur for up to several tens of
picoseconds. No longer-lasting transient absorption (TA) was found; instead, a
complete recovery of the ground state bleaching was observed indicating that
triplet state relaxation is either not significantly involved in this spectral
part or shifted to other regions. In the aqueous system, time constants for all
processes are much smaller than in organic solution, a fact that can be explained
by the larger dipole moment of the solvent and the correspondingly stronger
intermolecular coupling between NP- and the aqueous solvent.
PMID- 29340391
TI - Graphene on {116} faceted monocrystalline anatase nanosheet array for ultraviolet
detection.
AB - A structure composed of a nanosheet array may trap photons, which could be used
to enhance the optical response via resonances; this may be highly useful in
ultraviolet (UV) detection, photocatalysis, solar cells, etc. Moreover, anatase
nanosheets exposed with the active {001}, {111}, and {116} facets are promising
in applications such as Li-ion battery, photocatalysis, and electrochemistry.
Therefore, in this study, the {116} faceted single-crystalline anatase nanosheet
array with the sheet spacing in the range of several hundred nanometers was
directly grown on the transparent conductive substrates. A photo-detector was
fabricated by transferring a graphene electrode to the top of the anatase
nanosheet array. The resultant device is inactive to visible-light irradiation
and instantly responds to the UV light, which is due to the unique UV absorption
property of the anatase nanosheet array and the advantage of the Schottky
junction between the interfaces of graphene and anatase. The energy barrier
between the two materials is 0.122 eV. We have provided a thorough research on
graphene/monocrystal anatase-NSs.
PMID- 29340392
TI - Enhancing the photoluminescence of surface anchored metal-organic frameworks:
mixed linkers and efficient acceptors.
AB - We present two approaches to enhance the photoluminescence quantum yield (PLQY)
of surface-anchored metal-organic frameworks (SURMOFs). In the first approach we
fabricate SURMOFs from a mix of an emissive linker with an optically-inert linker
of equivalent length, diluting the emissive linker while maintaining the SURMOF
structure. This approach enhances the internal PLQY. However, the increase in
internal PLQY is achieved at the expense of a drastic reduction in optical
absorption, thus the external PLQY remains low. To overcome this limitation, a
second approach is explored wherein energy-accepting guest chromophores are
infiltrated into the framework of the active linker. At the correct acceptor
concentration, an internal PLQY of 52% - three times higher than the previous
approach - is achieved. Additionally, the absorption remains strong leading to an
external PLQY of 8%, an order of magnitude better than the previous approach.
Using this strategy, we demonstrate that SURMOFs can achieve PLQYs similar to
their precursor chromophores in solution. This is of relevance to SURMOFs as
emitter layers in general, and we examine the optimized emitter layer as part of
a photon upconversion (UC) SURMOF heterostructure. Surprisingly, the same PLQY is
not observed after triplet-triplet annihilation in the UC heterostructure as
after its normal photoexcitation (although the UC layers exhibit low thresholds
consistent with those reported in our previous work). We discuss the potential
bottlenecks in energy transport that could lead to this unexpected reduction in
PLQY after excitation via triplet-triplet annihilation, and how future design of
SURMOF UC multilayers could overcome these limitations.
PMID- 29340393
TI - Ferrocenyl-sulfonium ionic liquids - synthesis, characterization and
electrochemistry.
AB - New ferrocenylsulfonium cation based ionic liquids were prepared by direct
alkylation of the corresponding ferrocenyl-based thioethers with N
alkylbis(trifluoromethanesulfonyl)imides (R'TFSI). This convenient direct access
to organometallic sulfonium bis(trifluoromethanesulfonyl)imide (TFSI) salts
without the need for ion exchange was chosen in order to obtain highly pure and
reversibly redox active room temperature ILs in many cases. In other cases the
anion cation interaction in the solid state was studied by XRD analyses. Moreover
a diferrocenylmethylsulfonium tetrafluoroborate with two redox active centers was
synthesized. The redox chemistry of these sulfonium salts was investigated via
cyclic voltammetry. Furthermore, UV-Vis spectra and thermoanalytical data are
discussed. The electron-withdrawing sulfonium group is directly bonded to the
ferrocenyl unit, therefore this cationic group influences the potential of these
ionic liquids in a more pronounced way than being anchored to the ferrocenyl unit
via an organic spacer. With their low absorbance in the visible light and
reversible, tunable redox potential, these room temperature ILs open perspectives
as redox mediators in dye sensitized solar cells (DSSCs), as redox electrolytes
in supercapacitors or as overcharge protection additives in batteries.
PMID- 29340394
TI - Highly selective hydrosilylation of olefins and acetylenes by platinum(0)
complexes bearing bulky N-heterocyclic carbene ligands.
AB - Platinum complexes bearing bulky N-heterocyclic carbene (NHC) ligands, i.e.,
[Pt(IPr*)(dvtms)] (where, IPr* = 1,3-bis{2,6-bis(diphenylmethyl)-4
methylphenyl}imidazol-2-ylidene) and [Pt(IPr*OMe)(dvtms)] (where, IPr*OMe = 1,3
bis{2,6-bis(diphenylmethyl)-4-methoxyphenyl}imidazol-2-ylidene, dvtms =
divinyltetramethyldisiloxane) catalyse nearly quantitatively and highly or
completely the selective hydrosilylation of terminal olefins as well as terminal
or internal acetylenes.
PMID- 29340395
TI - Boosting electrocatalytic hydrogen evolution by plasmon-driven hot-electron
excitation.
AB - High-performance catalysts for electrocatalytic and photoelectrochemical water
splitting hold great promise for renewable energy conversion and storage. Herein,
using porous N-doped carbon supported Au nanoparticles as catalysts, we
demonstrate that the photon-induced localized surface plasmon resonance (LSPR)
excitation on Au nanoparticles dramatically improves the hydrogen evolution
reaction (HER), leading to a more than 4-fold increase of current and meanwhile
affording a markedly decreased overpotential of 99 mV at a current density of 10
mA cm-2. The HER enhancement can be largely attributed to the efficient charge
transfer of N-doped carbon that fastens the injection of hot electrons from
plasmonic Au nanoparticles. This study highlights the increase of HER catalysis
efficiency by plasmonic excitation and could provide new avenues towards the
design of higher energy conversion catalytic water splitting systems with the
assistance of light energy.
PMID- 29340396
TI - Synthesis and antiproliferative activity of a series of new platinum and
palladium diphosphane complexes.
AB - New organometallic complexes [M(dppe)(R)2] {where M = Pt or Pd, dppe = 1,2
bis(diphenylphosphano)ethane, and R = C6F4H-x (x = 6,5,4), C6F3H2-3,5, C6F3H2
5,6, C6F3H2-3,6, C6F4(OMe)-4, and C6F4(cyclo-C5H10N)-4, the numbers x refer to
the positions of the protons in the polyfluoroaryl ligands} were synthesised
either through transmetalation from the dichlorido complexes [M(dppe)Cl2] or
through ligand exchange using [M(diene)Cl2] precursor complexes with diene = 1,5
cyclooctadiene (cod) or 1,5-hexadiene (hex). Alternatively, [M(dppX)Cl(R)]
complexes with dppX = dppm (1,1-bis(diphenylphosphano)methane), dppe, dppp (1,3
bis(diphenylphosphano)propane), and dppb (1,4-bis(diphenylphosphano)butane) were
prepared in decarboxylation reactions from thallium(i) carboxylates Tl(O2CR). The
different preparative methods were compared in terms of yield and purity.
Structural and spectroscopic data are reported for the new dppX- and diene-M(R)2
complexes. Antiproliferative activity was investigated for these new complexes
against the HT-29 (colon carcinoma) and MCF-7 (breast adenocarcinoma) cell lines,
and the active compounds of this first series together with organometallic dppX
or hex PtII or PdII complexes were then included in cell tests using L1210
(leukaemia cells) and the cisplatin-resistant L1210/DDP cell line. Remarkably,
promising antiproliferative results were found for a few PtII and PdII complexes,
while structurally closely related compounds were essentially nontoxic.
PMID- 29340397
TI - Ligand modification of UiO-66 with an unusual visible light photocatalytic
behavior for RhB degradation.
AB - A series of isostructural UiO-66-X (X = H, NH2, Br, (OH)2, (SH)2) catalysts have
been successfully synthesized by modifying different functional groups on the
ligand. The effects of the ligand modification of UiO-66 were investigated for
their photocatalytic activity of Rhodamine B degradation under visible light.
Surprisingly, UiO-66-NH2 and UiO-66-(OH)2 which have narrow bandgaps and
excellent visible light absorption do not show outstanding photocatalytic
performances compared to UiO-66 and UiO-66-Br. Electrochemical test results
indicated that the conduction band potential of UiO-66-X and the separation
efficiency of electrons were quite important in these photocatalytic reactions,
other than the electronic effect as reported. Similar photocatalytic degradation
behaviors were found for Congo red and methyl orange. Herein, we firstly reported
different mechanisms of selective degradation in the case of UiO-66, which
subverted the previous understanding of photodegradation behavior.
PMID- 29340398
TI - Synthesis and crystal structure of Sr3Bi2O6 and structural change in the
strontium-bismuth-oxide system.
AB - The crystal structures and their changing trend in the strontium-bismuth-oxide
system are critical for the studies of the related systems and their
applications. The crystal structure of Sr3Bi2O6 was obtained for the first time
in the space group of R3[combining macron] with a huge unit cell of a = b =
25.1146(19) A and c = 18.3685(16) A and all bismuth ions are Bi3+ forming [BiO3]
trigonal pyramids. Sr3Bi2O6 is a key compound for the structural change trend in
the SrO-Bi2O3 binary oxide system at 1000 degrees C. With a decrease in the
bismuth content, its valence state changes from +3 to +5 and Bi-O polyhedra
changes from connected to isolated before Bi(v) appearance. In the system, the
boundary of the solid solution beta-phase (Sr1-xBixO1+0.5x) at 900 degrees C was
also determined accurately as 0.770 <= x <= 0.862, experimentally.
PMID- 29340399
TI - Landscape of gene networks for random parameter perturbation.
AB - Landscape approaches have been exploited to study the stochastic dynamics of gene
networks. However, how to calculate the landscape with a wide range of parameter
variations and how to investigate the influence of the network topology on the
global properties of gene networks remain to be elucidated. Here, I developed an
approach for the landscape of random parameter perturbation (LRPP) to address
this issue. Based on a self-consistent approximation approach, by making
perturbations to parameters in a given range, I obtained the landscape for gene
network systems. I applied this approach to two biological models, one for the
mutual repression model and the other for the embryonic stem (ES) cell
differentiation network. For the mutual repression model, my results confirm
quantitatively that positive feedback promotes the robustness of multistability.
For the ES cell differentiation model, I identify three cell states, representing
the ES cell, the differentiation cell, and the intermediate state cell,
respectively. I propose that the intermediate states and the wide range of
parameter values coming from inhomogeneous cellular environments provide possible
explanations for the heterogeneity observed in single cell experiments. I also
offer a counterintuitive result that noise could reduce heterogeneity and promote
the stability of cell states. These results support that the network topology
determines the operating principles of the genetic networks, reflected by the
representative landscapes from LRPP. This work provides a new route to obtain the
potential landscape for a gene network system given a wide range of parameter
values and study the influences of the network topology on the global properties
of the system.
PMID- 29340400
TI - Femtosecond laser induced underwater superaerophilic and superaerophobic PDMS
sheets with through microholes for selective passage of air bubbles and further
collection of underwater gas.
AB - Controlling underwater bubble behavior on a solid surface is of great research
significance, particularly in extreme cases. However, the realization of
artificial underwater superaerophobic or superaerophilic surfaces is still a
challenge. Herein, a micro/nanoscale hierarchical rough structure was formed on
polydimethylsiloxane (PDMS) surface by one-step femtosecond laser ablation. The
as-prepared surface showed superhydrophobicity in air and superaerophilicity in
water. Interestingly, the wettability of such a PDMS surface could be easily
switched to in-air superhydrophilicity and underwater superaerophobicity once it
was further irradiated by oxygen plasma because the surface chemistry changed.
The original femtosecond laser-structured underwater superaerophilic PDMS surface
could absorb/capture bubbles, while the plasma-treated underwater superaerophobic
surface had excellent anti-bubble ability in water. A rough through-microhole
array PDMS sheet was prepared by a mechanical drilling process and subsequent
femtosecond laser ablation. The sheet could selectively allow bubbles to pass,
that is, the porous underwater superaerophilic sheet allowed bubbles to pass
through, while the porous underwater superaerophobic sheet was able to intercept
bubbles in a water medium. Using the porous underwater superaerophilic PDMS sheet
as the core component, a device that has great ability of collecting underwater
bubbles/gas was also designed.
PMID- 29340401
TI - A nanopaper-based artificial tongue: a ratiometric fluorescent sensor array on
bacterial nanocellulose for chemical discrimination applications.
AB - In the present study, a ratiometric fluorescent sensor array as an artificial
tongue has been developed on a nanopaper platform for chemical discrimination
applications. The bacterial cellulose (BC) nanopaper was utilized for the first
time as a novel, flexible, and transparent substrate in the optical sensor arrays
for developing high-performance artificial tongues. To fabricate this platform,
the hydrophobic walls on the BC nanopaper substrates were successfully created
using a laser printing technology. In addition, we have used the interesting
photoluminescence (PL) properties of an immobilized ratiometric probe (carbon dot
Rhodamine B (CD-RhB) nanohybrids) on the nanopaper platform to improve the visual
discrimination analysis. Heavy metal ions were utilized as model analytes to
verify the applicability of the fabricated nanopaper-based ratiometric
fluorescent sensor array (NRFSA). Using the color variation of the NRFSA platform
upon the addition of heavy metal ions, which have been obtained by a smartphone
(under an UV irradiation), five heavy metal ions (i.e., Hg(ii), Pb(ii), Cd(ii),
Fe(iii), and Cu(ii)) have been well-distinguished through the RGB analysis via
production of the characteristic PL fingerprint-like response patterns for each
of them. Moreover, the developed optical sensor array was successfully exploited
to identify the heavy metal ions in the water and fish samples. We have also
found that the PL spectra, which have been obtained by a spectrofluorometer, of
the developed NRFSA can be exploited for discrimination applications. We believe
that the nanopaper-based artificial tongues will provide innovative insights into
the development of optical sensor arrays towards advanced (bio)chemical
discrimination applications and can revolutionize the conventional optical sensor
array technology.
PMID- 29340402
TI - Palladium-catalysed stereoselective synthesis of 4-(diarylmethylidene)-3,4
dihydroisoquinolin-1(2H)-ones: expedient access to 4-substituted isoquinolin
1(2H)-ones and isoquinolines.
AB - An efficient method has been developed for the stereoselective synthesis of 4
(diarylmethylidene)-3,4-dihydroisoquinolin-1(2H)-ones 7 through tandem Heck
Suzuki coupling at rt using easily available substrates. DBU easily converted the
exocyclic double bond of these compounds to endo, furnishing 8 and 9. Reduction
of the carbonyl group of 7 was smoothly carried out with borane dimethyl
sulphide. Subsequent treatment with KOtBu provided an easy access to 4
substituted isoquinolines 10a if carried out in refluxing 1,4-dioxane, while
reaction in DMF at rt led to the incorporation of an extra hydroxyl group at the
benzylic position of the isoquinolines to give 10b. This straightforward and
metal free procedure would serve as a better alternative to the prevalent
procedures. Few of the products could also be transformed into heterocyclic
scaffolds structurally resembling known bioactive compounds.
PMID- 29340403
TI - Triangular AgAu@Pt core-shell nanoframes with a dendritic Pt shell and enhanced
electrocatalytic performance toward the methanol oxidation reaction.
AB - Triangular AgAu@Pt nanoframes with a dendritic Pt shell were synthesized by
employing Ag nanoprisms as sacrificial templates. Due to the unique frame-like
nanostructure and ternary components, the AgAu@Pt nanoframes exhibit impressive
electrocatalytic performance toward the methanol oxidation reaction with much
higher activity, and better anti-poisoning capability than commercial Pt/C
catalysts.
PMID- 29340404
TI - A highly efficient nucleophilic substitution reaction between R2P(O)H and
triarylmethanols to synthesize phosphorus-substituted triarylmethanes.
AB - A highly efficient and general nucleophilic substitution reaction between dialkyl
H-phosphonates or diarylphosphine oxides and triarylmethanols catalyzed by HOTf
(trifluoromethanesulfonic acid) has been developed. It provides an atom
economical protocol for the synthesis of various symmetrical and unsymmetrical
phosphorus-substituted triarylmethanes that constitute an emerging family of
potent anticancer agents in rich diversity with 40 to 96% yields. The synthetic
applicability of this protocol is demonstrated by gram-scale preparations.
PMID- 29340405
TI - Modulating interactions between ligand-coated nanoparticles and phase-separated
lipid bilayers by varying the ligand density and the surface charge.
AB - The interactions between nanoparticles and lipid bilayers are critical in
applications of nanoparticles in nanomedicine, cell imaging, toxicology, and
elsewhere. Here, we investigate the interactions between nanoparticles coated
with neutral and/or charged ligands and phase-separated lipid bilayers using
coarse-grained molecular dynamics simulation. Both penetration and adsorption
processes as well as the final distribution of the nanoparticles can be readily
modulated by varying the ligand density and the surface charge of the
nanoparticles. Completely hydrophobic (neutral) nanoparticles with larger size
initially preferentially penetrate into the liquid-disordered region of the lipid
bilayer and finally transfer into the liquid-ordered region; partially
hydrophilic nanoparticles with low or moderate surface charge tend to either
distribute in the liquid-disordered region or be adsorbed on the surface of the
lipid bilayer, while strongly hydrophilic nanoparticles with high surface charge
always reside on the surface of the lipid bilayer. Interactions of the
nanoparticles with the lipid bilayers are affected by the surface charge of
nanoparticles, hydrophobic mismatch, bending of the ligands, and the packing
state of the lipids. Insight in these factors can be used to improve the
efficiency of designing nanoparticles for specific applications.
PMID- 29340406
TI - Clarifying the high on/off ratio mechanism of nanowire UV photodetector by
characterizing surface barrier height.
AB - The response of semiconductor nanowire UV sensors represented by ZnO nanowire UV
sensor is usually explained by the adsorption and desorption of oxygen molecules,
but with the great increase of these sensors' on/off ratio in recent years, this
explanation is inadequate and the inner mechanism for the large on/off ratio
urgently needs to be explored. Here, the distribution of carrier concentration in
a ZnO nanowire is found to be determined as a function of the radius of the
nanowire, using a calibrated surface photovoltage method and space charge model.
A critical radius is indicated which determines the carrier concentration and
photoresponse behavior of the nanowire. When the radius is below this critical
value, the carrier concentration in the dark decreases dramatically compared with
that of the nanowire under UV light illumination. Specifically, a decrease of
carrier concentration by 4-5 orders of magnitude occurs when the radius is below
50 nm, which causes the on/off ratio to vary by the same orders of magnitude.
When the radius is above the critical value, the influence of radius on carrier
concentration is nonsignificant and the on/off ratio is below 100. Finally, we
found that the high on/off ratio of the ZnO nanowire should be ascribed to the
complete depletion of the nanowire led by the interplay of radius and surface
band bending rather than the change in width of the depletion layer as most
papers have suggested.
PMID- 29340407
TI - t-BuONa-mediated direct C-H halogenation of electron-deficient (hetero)arenes.
AB - An efficient halogenation of electron-deficient (hetero)arenes is described. The
reaction utilizes common t-BuONa as a catalyst (for iodination) or a promoter
(for bromination and chlorination), and perfluorobutyl iodide, CBr4 or CCl4 as
the readily-available halogenating agents, respectively. The protocol features
broad scope, high efficiency, mild conditions and gram scalability. An ionic
pathway involving halogen bond formation and halophilic attack is proposed. The
utility of the resulting iodinated heteroarenes is demonstrated in visible light
mediated Caryl-Caryl cross-coupling reaction.
PMID- 29340408
TI - Expanding pore sizes of ZIF-8-derived nitrogen-doped microporous carbon via C60
embedding: toward improved anode performance for the lithium-ion battery.
AB - Porous carbon and nanocarbons have been extensively applied as anode materials
for high-energy density lithium-ion batteries (LIBs). However, as another
representative nanocarbon, fullerenes, such as C60, have been scarcely utilized
in LIBs because of their poor electrochemical reversibility. Herein, we designed
a novel C60-embedded nitrogen-doped microporous carbon material (denoted as C60@N
MPC), which was derived from a zeolitic imidazolate framework-8 (ZIF-8)
precursor, demonstrating its promising application as a superior anode material
for LIB. We first embedded C60in situ into a ZIF-8 matrix via a facile solid
state mechanochemical route, which acted as a precursor and was transformed to
C60@N-MPC after carbonization. The C60@N-MPC was applied as a novel anode for
LIBs, showing an improved reversible specific capacity of ~1351 mA h g-1 at 0.1 A
g-1 and a better rate capacity (~1077 mA h g-1 at 1 A g-1 after 400 cycles)
relative to those based on the unmodified N-MPC anode. The role of C60 in the
superior lithium storage performance of C60@N-MPC was elucidated, revealing that
C60 functioned as a pore expander for N-MPC with 3-20 nm mesopores (versus sub-1
nm micropores for the unmodified N-MPC), which facilitated the rapid diffusion of
the organic electrolyte.
PMID- 29340410
TI - Active textiles with Janus fibres.
AB - We describe reshaping of active textiles actuated by bending of Janus fibres
comprising both active and passive components. A great variety of shapes,
determined by minimising the overall energy of the fabric, can be produced by
varying bending directions determined by the orientation of Janus fibres. Under
certain conditions, alternative equilibrium states, one absolutely stable and the
other metastable coexist, and their relative energy may flip its sign as system
parameters, such as the extension upon actuation, change. A snap-through
reshaping in a specially structured textile reproduces the Venus flytrap effect.
PMID- 29340409
TI - Dynamics of 3D carcinoma cell invasion into aligned collagen.
AB - Carcinoma cells frequently expand and invade from a confined lesion, or
multicellular clusters, into and through the stroma on the path to metastasis,
often with an efficiency dictated by the architecture and composition of the
microenvironment. Specifically, in desmoplastic carcinomas such as those of the
breast, aligned collagen tracks provide contact guidance cues for directed cancer
cell invasion. Yet, the evolving dynamics of this process of invasion remains
poorly understood, in part due to difficulties in continuously capturing both
spatial and temporal heterogeneity and progression to invasion in experimental
systems. Therefore, to study the local invasion process from cell dense clusters
into aligned collagen architectures found in solid tumors, we developed a novel
engineered 3D invasion platform that integrates an aligned collagen matrix with a
cell dense tumor-like plug. Using multiphoton microscopy and quantitative
analysis of cell motility, we track the invasion of cancer cells from cell-dense
bulk clusters into the pre-aligned 3D matrix, and define the temporal evolution
of the advancing invasion fronts over several days. This enables us to identify
and probe cell dynamics in key regions of interest: behind, at, and beyond the
edge of the invading lesion at distinct time points. Analysis of single cell
migration identifies significant spatial heterogeneity in migration behavior
between cells in the highly cell-dense region behind the leading edge of the
invasion front and cells at and beyond the leading edge. Moreover, temporal
variations in motility and directionality are also observed between cells within
the cell-dense tumor-like plug and the leading invasive edge as its boundary
extends into the anisotropic collagen over time. Furthermore, experimental
results combined with mathematical modeling demonstrate that in addition to
contact guidance, physical crowding of cells is a key regulating factor
orchestrating variability in single cell migration during invasion into
anisotropic ECM. Thus, our novel platform enables us to capture spatio-temporal
dynamics of cell behavior behind, at, and beyond the invasive front and reveals
heterogeneous, local interactions that lead to the emergence and maintenance of
the advancing front.
PMID- 29340411
TI - Multiplexed detection of nucleic acids using 19F NMR chemical shift changes based
on DNA photo-cross-linking of 3-vinylcarbazole derivatives.
AB - The detection methodology for nucleic acids is a useful tool for the analysis of
biological systems and diagnosis of diseases. We demonstrated the feasibility of
the detection of any nucleic acids based on large chemical shifts via ultrafast
DNA photo-cross-linking and the effects of substitution by 3-vinylcarbazole
derivatives. These chemical shifts enable the sequence-specific detection of any
strand using hybridization chain reaction.
PMID- 29340413
TI - Stretch tuning of the Debye ring for 2D photonic crystals on a dielectric
elastomer membrane.
AB - The tunable diffracted pattern (Debye ring) of the well-ordered close-packed 2D
photonic crystal (PC) is achieved via large deformation of the dielectric
elastomer (DE) membrane for the first time. Two deformation models are proposed,
the in-plane deformation driven by voltage and the out-of-plane deformation
actuated by pressure. Both experimental and theoretical analyses are conducted to
explore the tunability of the DE stretch on the Debye ring of the 2D PC, by
voltage and pressure. An excellent agreement is found between the experimental
and analytical results. This study shows that tuning the size of the Debye ring
by voltage driven in-plane deformation is easy to operate and space-saving.
However, it needs a high voltage and the adjustable range is relatively small. On
the other hand, the pneumatic tuning by out-of-plane deformation has a widely
adjustable range compared with the electric one and the pressure needed is only
hundreds to less than two thousand pascal, which is energy-saving. This work may
pave the way for the design of various smart sensors and soft displays with the
combination of PCs and DEs.
PMID- 29340414
TI - Nanoparticle separation based on size-dependent aggregation of nanoparticles due
to the critical Casimir effect.
AB - Nanoparticles typically have an inherent wide size distribution that may affect
the performance and reliability of many nanomaterials. Because the synthesis and
purification of nanoparticles with desirable sizes are crucial to the
applications of nanoparticles in various fields including medicine, biology,
health care, and energy, there is a great need to search for more efficient and
generic methods for size-selective nanoparticle purification/separation. Here we
propose and conclusively demonstrate the effectiveness of a size-selective
particle purification/separation method based on the critical Casimir force. The
critical Casimir force is a generic interaction between colloidal particles near
the solvent critical point and has been extensively studied in the past several
decades due to its importance in reversibly controlling the aggregation and
stability of colloidal particles. Combining multiple experimental techniques, we
found that the critical Casimir force-induced aggregation depends on relative
particle sizes in a system with larger ones aggregating first and the smaller
ones remaining in solution. Based on this observation, a new size-dependent
nanoparticle purification/separation method is proposed and demonstrated to be
very efficient in purifying commercial silica nanoparticles in the lutidine/water
binary solvent. Due to the ubiquity of the critical Casimir force for many
colloidal particles in binary solvents, this method might be applicable to many
types of colloidal particles.
PMID- 29340415
TI - Alkaline-earth metal phenylphosphonates and their intercalation chemistry.
AB - The intercalation chemistry of layered alkaline-earth metal phenylphosphonates
with the general formula MeC6H5PO3.2H2O (Ca, Sr, Ba) is reviewed. The preparation
of the host materials is described and their behavior in dependence on the
relative humidity and pH of the reaction medium is discussed. Mutual
relationships between MeC6H5PO3.2H2O and Me(C6H5PO3H)2 were investigated using a
method of computer-controlled addition of reagents. The MeC6H5PO3.2H2O compounds
are able to intercalate species having a free electron pair through the so-called
coordination intercalation. In this way, 1-alkylamines, 1-alkanols, 1,n-diols and
1,2-diols were intercalated. In the case of the ethanol and methanol intercalates
of strontium phenylphosphonate we were able to determine the structure of the
host part by single-crystal X-ray diffraction. By combination of the data
obtained from the diffraction with molecular modeling we suggested the
arrangement of the host molecules in the interlayer space of the host. The
arrangement of the shorter diols in the interlayer space of strontium
phenylphosphonate was also proposed on the basis of molecular modeling
calculations. These models help us to understand the structure of the prepared
intercalates.
PMID- 29340416
TI - Self-assembly of cationic gemini surfactants, alkanediyl-bis-(dimethyldodecyl
ammonium bromide), in cyclohexane: effects of spacer length on their association
into reverse lyotropic liquid crystalline or reverse vesicles.
AB - Herein, homogeneous solutions of cationic gemini surfactants, alkanediyl
alpha,omega-bis(dimethyldodecylammonium bromide), referred to as 12-s-12 where s
= 2, 4, 6, 8, and 10, in cyclohexane have been prepared with the help of sodium
hexanoate (SH) or sodium laurate (SL). These surfactants self-assembled in
cyclohexane to form various aggregating structures, which were characterised by
small-angle X-ray scattering (SAXS) together with polarised microscopy
observations. The results showed that 12-2-12/SH, where the gemini had the
shortest spacer among this series, formed an inverse micellar cubic liquid
crystalline phase of the Fd3m structure. 12-s-12/SL, including s = 4, 6, and 8,
which contained an adequate length spacer, formed an inverse hexagonal liquid
crystalline phase packed by the cylindrical assemblies of surfactants. 12-10
12/SL, in which the gemini had a longer spacer, formed dispersed reverse vesicles
(a lamellar structure). The rheological properties of liquid crystalline phases
in a linear visco-elastic regime were studied. 12-2-12/SH formed a hard gel,
whereas 12-s-12/SL formed soft gels. Dynamic light scattering and steady-state
viscosity analyses were performed for the reverse vesicle solutions formed by 12
10-12/SL. In all these systems, the amount of added water W0, denoting the mole
ratio of water to the gemini surfactant, was demonstrated to influence the
properties.
PMID- 29340417
TI - Rose Bengal catalysed photo-induced selenylation of indoles, imidazoles and
arenes: a metal free approach.
AB - In this report, the highly efficient Rose Bengal-catalysed C(sp2)-H selenylation
of indoles, imidazoles and arenes was achieved using a half molar equiv. of
diorganoyl diselenides. This metal-free, photo-induced protocol resulted in
selenylated products in good to excellent yields. The reaction features are high
yields, an atom-economic, gram-scalable and metal-free approach, and
applicability to different biologically relevant (hetero)arenes.
PMID- 29340423
TI - Total synthesis of five natural eremophilane-type sesquiterpenoids.
AB - The first total syntheses of five natural eremophilane-type sesquiterpenoids were
achieved in 4-12 steps via a common synthetic intermediate. The syntheses feature
a double Michael addition, Robinson annulation, alpha-enolization of an
unsaturated ketone, and Pd-catalyzed Suzuki coupling reaction to install the side
chain. This synthetic strategy could be easily extended to other eremophilane
type sesquiterpenoids with similar bicyclic skeletons.
PMID- 29340428
TI - A synergic approach of X-ray powder diffraction and Raman spectroscopy for
crystal structure determination of 2,3-thienoimide capped oligothiophenes.
AB - This work presents a Raman based approach for the rapid identification of the
molecular conformation in a series of new 2,3-thienoimide capped
quaterthiophenes, whose crystal structures were determined by synchrotron
radiation X-ray powder diffraction. These systems display two conformational
polymorphs, known as forms A and B, as a result of the anti-anti-anti and syn
anti-syn arrangements of the quaterthiophene cores. In a micro-Raman and
computational study, the spectroscopic differences between the conformers were
detected and proved to be suitable markers for polymorph identification. Thus,
the synergic employment of diffraction and Raman spectroscopy techniques yields a
full and reliable characterization of 2,3-thienoimide capped quaterthiophene
compounds in their solid state.
PMID- 29340432
TI - Capture of colloidal particles by a moving microfluidic bubble.
AB - Foams can be stabilized for long periods by the adsorption of solid particles on
the liquid-gas interfaces. Although such long-term observations are common,
mechanistic descriptions of the particle adsorption process are scarce,
especially in confined flows, in part due to the difficulty of observing the
particles in the complex gas-liquid dispersion of a foam. Here, we characterise
the adsorption of micron-scale particles onto the interface of a bubble flowing
in a colloidal aqueous suspension within a microfluidic channel. Three parameters
are systematically varied: the particle size, their concentration, and the mean
velocity of the colloidal suspension. The bubble coverage is found to increase
linearly with position in the channel for all conditions but with a slope that
depends on all three parameters. The optimal coverage is found for 1 MUm
particles at low flow rates and high concentrations. In this regime the particles
pass the bubbles through the gutters between the interface and the channel
corners, where the complex 3D flow leads them onto the interface. The largest
particles cannot enter into the gutters and therefore provide very poor coverage.
In contrast, particle aggregates can sediment onto the microchannel floor ahead
of the bubble and get swept up by the advancing interface, thus improving the
coverage for both large and medium particle sizes. These observations provide new
insight on the influence of boundaries for particle adsorption at an air-liquid
interface.
PMID- 29340434
TI - Structure-induced switching of interpolymer adhesion at a solid-polymer melt
interface.
AB - Here we report a link between the interfacial structure and adhesive property of
homopolymer chains physically adsorbed (i.e., via physisorption) onto solids.
Polyethylene oxide (PEO) was used as a model and two different chain
conformations of the adsorbed polymer were created on silicon substrates via the
well-established Guiselin's approach: "flattened chains" which lie flat on the
solid and are densely packed, and "loosely adsorbed polymer chains" which form
bridges jointing up nearby empty sites on the solid surface and cover the
flattened chains. We investigated the adhesion properties of the two different
adsorbed chains using a custom-built adhesion testing device. Bilayers of a thick
PEO overlayer on top of the flattened chains or loosely adsorbed chains were
subjected to the adhesion test. The results revealed that the flattened chains do
not show any adhesion even with the chemically identical free polymer on top,
while the loosely adsorbed chains exhibit adhesion. Neutron reflectivity
experiments corroborated that the difference in the interfacial adhesion is not
attributed to the interfacial brodening at the free polymer-adsorbed polymer
interface. Instead, coarse-grained molecular dynamics simulation results suggest
that the tail parts of the loosely adsorbed chains act as "connector molecules",
bridging the free chains and substrate surface and improving the interfacial
adhesion. These findings not only shed light on the structure-property
relationship at the interface, but also provide a novel approach for developing
sticking/anti-sticking technologies through precise control of the interfacial
polymer nanostructures.
PMID- 29340436
TI - Dietary pectin and mango pulp effects on small intestinal enzyme activity levels
and macronutrient digestion in grower pigs.
AB - The effects of refined pectin and mango pulp on macronutrient digestion and small
intestinal enzyme activity were studied in grower pigs. Diets based on wheat
starch with and without apple pectin or dried mango fruit pulp were fed to 30
grower pigs for 21 days. Pigs were euthanized two hours postprandially, and their
gastrointestinal contents recovered. Starch and protein digestion as well as
alpha-amylase activity were all increased in pigs fed pectin. In contrast, fat
digestion, lipase and protease (trypsin) activities were all significantly
reduced in these pigs. Pigs fed the mango fruit pulp diet had intermediate
effects compared with pigs fed refined pectin and control diets. The data
suggests that pectin has a significant effect on digestive enzyme activity and
subsequent influence on macronutrient digestion. The fact that pectin caused
either an increase (alpha-amylase) or decrease (lipase, protease) in enzyme
activity in digesta, which either did (starch, lipid) or did not (protein)
associate with residual nutrient differences illustrates the complexity of small
intestinal responses to added fibre in diets.
PMID- 29340437
TI - A novel lysosome-targeted fluorogenic probe based on 5-triazole-quinoline for the
rapid detection of hydrogen sulfide in living cells.
AB - A fluorogenic probe based on the novel fluorophore 5-triazole-quinoline was
developed for the detection of hydrogen sulfide, an endogenous signaling molecule
associated with the development of various diseases. The lysosome-targeted probe
Lyso-HS was synthesized via C-H direct azidation from 8-aminoquinoline; it was
able to detect H2S in 1 min and exhibited excellent turn-on ability with 95-fold
fluorescence enhancement based on a new fluorochrome. The high quenching
efficiency was further verified using time-dependent density functional theory
(TDDFT). The probe also exhibited high selectivity and a low detection limit (as
low as 214.5 nM), which has practical applications for disease detection and
monitoring.
PMID- 29340438
TI - [Human rights and democracy in Argentina: challenges for a future agenda].
PMID- 29340439
TI - [Origin of the scientific arguments underlying qualitative research].
AB - This article analyzes the origin of the primary arguments that underpin the
qualitative approach, covering the birthplace of comprehensive and dialectical
thought in Germany, its expansion into other countries such as France and the
United States, and its spread into Latin America. The historical journey of the
text starts with the development of modern science, examining the first empirical
works in the Chicago School and the subsequent period of ostracism of qualitative
research. The text also evidences a revival of comprehensive theoretical and
empirical perspectives from the 1960s onwards, accompanying the cultural movement
that came to question the great theoretical narratives and give rise to
reflections on subjectivity. Theoretically, qualitative approaches are now
considered a promising form of knowledge construction within the social and human
sciences, with consolidated theories and a process of permanent internal
critique. Such consolidation is ensured by the researchers' formation of
conferences and university departments, the existence of books for the training
of new researchers, and the increased presence of relevant spaces in scientific
journals.
PMID- 29340440
TI - [Administration: practices, myths and ideologies].
AB - Administration in the social field is examined based on an analysis of its
practices, the rationalist myth and its ideological dimensions. In this way, the
article discusses the most frequently utilized concepts (administration,
management, gerencia, gestion) and their etymologies; the limitations of teaching
administration; the complexity of a practice marked by the dimensions of science,
art and the social game; and the ideological question underlying the great
thought factory that the general theory of administration has been since the
start of the 19th century. The article reflects upon the need to construct a
theory based in practice contextualized in the global south that goes beyond the
classic frames of reference and, above all, to transform administration into a
problem to be discussed outside of the knowledge that recognizes it as a
technical practice.
PMID- 29340441
TI - [Theoretical reflections regarding subjects of praxis and subjects of antithesis
in Brazilian health reform].
AB - The Brazilian Health Reform has been recognized as a project that transcends the
sectoral dimension in that it considers an expanded concept of health and social
determination, which distinguishes it from other health system reforms of the
twentieth century. This article aims to contribute to the construction of the
concepts subjects of praxis and subjects of antithesis by discussing certain
challenges of praxis in the Brazilian Health Reform, the constitution of social
subjects and the emergence of subjects of antithesis. The article argues that
theoretical reflection can contribute to political analysis in health and discern
the power of a praxis that destabilizes the conservative character of the passive
revolution.
PMID- 29340442
TI - [Psychological violence against women: What factors increase the risk of this
kind of intimate partner abuse?]
AB - Using data from Argentina's National Study on Violence Against Women [Estudio
nacional sobre violencias contra las mujeres] carried out in 2015, the article
identifies the risk factors that increase women's vulnerability to psychological
abuse. Findings show that women who are more prone to be victims of this kind of
partner violence are those who are less educated, older, do not earn a wage for
their work, live with children at home, are involved in less "formal" long-term
relationships, as well as those whose male partners have a lower educational
level than their own and/or have alcohol problems and/or were victims or
witnesses of violence during their childhood. The article suggests possible
intervention strategies to eradicate abuse, which should be primarily targeted at
empowering women and strengthening their independence from their partners.
PMID- 29340443
TI - [Gender performativity, medicalization and health in transsexual women in Mexico
City].
AB - The World Health Organization and the American Psychological Association consider
transsexuality a pathology and suggest sex-gender reassignment for the biopsychic
adjustment of trans people. Through the discursive analysis of experience, this
study describes the processes of medicalization and gender performativity in
relation to the health of a group of trans women from Mexico City. For this
purpose, a qualitative study was conducted in which 10 semi-structured interviews
were carried out in 2015. As part of medicalization, the pathologization of
transsexuality generated psychic suffering; on the other hand, sex-gender
reassignment also entailed additional risks. It is possible to conclude that in
trans women, violence and exclusion constitute the primary experiences explaining
their foremost health problems. Therefore, it is suggested that it is necessary
for discrimination be reduced and for advancements to be made in safer medical
interventions.
PMID- 29340444
TI - [Mortality due to hypertensive diseases: evidence from the southern border of
Mexico in the period 1998-2014].
AB - This article analyzes patterns of mortality due to hypertensive diseases in the
southern border of Mexico, as well as the evolution of such mortality in the 1998
2014 period. The emphasis is directed at the causes "Essential (primary)
hypertension" (I10X) and "Hypertensive heart disease with heart failure" (I110).
Using data from the mortality records of the National Health Information System,
two types of analyses were carried out: cross-sectional analysis and time trends.
Over the 16 years included in the study, the age-adjusted mortality rates show a
clear increase. The findings suggest that the higher presence of indigenous
populations is a trait of importance in the determination of the mortality
pattern, with the state of Yucatan a case of particular interest. In addition, it
is the female population that which exhibits the greatest adverse impact.
PMID- 29340445
TI - [Health universalism in Argentina between 2003 and 2015: assessments and
challenges based in a macro-institutional approach].
AB - Debates about universalism in health have been gaining ground in Latin America
and have entered the policy agenda with differing results. Notwithstanding the
country's federalism, the most profound changes that took place in Argentina in
the last decade occurred in the arena of national politics. Based on the
theoretical contributions of historical neo-institutionalism and implementation
studies, this paper aims to analyze, from a macro institutional approach, the
scope of the national policy regarding health universalization. This descriptive
study is based on secondary sources and the review of research results on the
implementation of the programs Remediar, Sumar and Plan Nacer in relation to four
variables: coverage, access, sets of benefits and rights included in the policy.
Given the characteristics of the Argentine institutional matrix, program
implementation in subnational scenarios can be expected to confront complex and
heterogeneous terrain in which the programs acquire new meanings with respect to
the goal of universality that each poses.
PMID- 29340446
TI - [Tensions and contradictions in government interventions for the promotion of
breastfeeding].
AB - With the purpose of shedding light on the decrease in the practice of
breastfeeding in rural areas of Mexico, this article looks at the current
biomedical model and the policies and actions to promote breastfeeding derived
from the model's theoretical approach. The article also discusses operational
strategies of the governmental social welfare program Oportunidades. For this
purpose, the study utilizes the testimonies of 39 young breastfeeding mothers, 11
mothers and grandmothers and 12 members of the health staff in the Nahuatl
population of Cuentepec, Morelos, Mexico, which were collected during a previous
study in 2008 and 2009. It was found that the biomedical model, which permeates
all actions to promote breastfeeding, reifies people, limits communication,
devaluates women's traditional knowledge and imposes a discourse that gradually
discourages the practice of breastfeeding. The article's proposal is to adopt an
epistemic change in biomedical thought that shifts from a paradigm of simplicity
to one of complexity, with the purpose of achieving a greater understanding of
the bio-psycho-socio-cultural processes of human beings.
PMID- 29340447
TI - [Why don't doctors use early insulinization therapy in patients with diabetes
mellitus type 2?: A qualitative approach in a Mexican city].
AB - Early insulinization therapy is regarded as an efficient aid to improve long term
control and quality of life in patients with diabetes mellitus type 2 (DM2).
Nevertheless, both patients and medical staff confront barriers in using this
therapeutic tool. This study employs a qualitative approach to explore the
barriers to early insulinization among medical staff from the public sector in
the city of Xalapa, Veracruz, Mexico. Between 2015 and 2016, in-depth interviews
were conducted with general and specialist physicians offering primary health
care to patients with DM2. The transcribed interviews were analyzed to extract
and organize categories and subcategories of barriers among medical staff. These
barriers were then grouped into three categories and exemplified with interview
excerpts: barriers coming from the medical staff itself, barriers emerging from
the doctor-patient interaction, and institutional barriers. Uses for the
classification obtained are discussed, as are some of the solutions proposed by
study participants.
PMID- 29340448
TI - [Uses of madness: towards the recognition of new interpretations of human
suffering].
AB - This article addresses the controversy associated with the construct
schizophrenia/psychosis/madness, indicating the need to acknowledge the
multiplicity of experiences and interpretations which arise through the use of
the construct. The plurality and complexity intrinsic to the phenomenon, the
discrepancies in its possible meanings and the value of first-hand experience are
indicated as aspects whose recognition is indispensable to both understanding
suffering and confronting it socio-educationally. Using interviews carried out in
September 2013 and May 2014 with six people diagnosed at least with
schizophrenia, who gave their informed consent to participate, these dimensions
are explored. Additionally, madness is examined from a queer perspective as a
possible space of political expression that permits new paths and forms of social
circulation among those afflicted.
PMID- 29340449
TI - The continuous challenge of Chagas disease treatment: bridging evidence-based
guidelines, access to healthcare, and human rights.
PMID- 29340450
TI - Therapeutic drug monitoring of benznidazole and nifurtimox: a systematic review
and quality assessment of published clinical practice guidelines.
AB - The pharmacological management of adults with chronic-phase Chagas disease is
challenging despite it being the recent focus of extensive research. One of the
challenges in the current clinical practice guidelines (CPGs) landscape is the
existence of non-evidence-based recommendations for the use of laboratory tests
in treatment monitoring. This study aimed to systematically assess the quality
and consistency of recommendations of CPGs on the pharmacological management of
adults with chronic-phase Chagas disease. Systematic literature searches were
conducted in MEDLINE, EMBASE, SciELO and Google to identify all published CPGs
relevant to the pharmacological management of Chagas disease, between January
2010 and March 2016. Three independent reviewers assessed the quality of each CPG
using the Appraisal of Guidelines Research and Evaluation (AGREE) II instrument.
A total of five CPGs were included and the overall quality of the guidelines for
therapeutic drug monitoring of Chagas disease was moderate-to-low. There was
considerable variation in the quality of the CPGs across the AGREE II domains.
The domains of scope/purpose, stakeholder involvement, and clarity of
presentation were rated well, and the domains of applicability and editorial
independence received poor ratings. This review showed that the methodological
quality of CPGs for Chagas disease was generally inappropriate, and there was no
explicit link between the best available evidence and current recommendations.
PMID- 29340451
TI - Is waste collection associated with hepatitis B infection? A meta-analysis.
AB - This meta-analysis, which is based on a previously published systematic review,
aims to contribute to the scientific discussion on hepatitis B virus (HBV)
infection in workers who are exposed to domestic and healthcare wastes.
Publications were sought which had been made available on the data used by
December 2013 and updated to December 2016. The quality of the included studies
was assessed according to the guidelines of Loney et al. for the critical
appraisal of studies on the prevalence or incidence of a health problem. To
verify the presence of heterogeneity between the papers, we used the Chi-squared
test based on a Q statistic. A funnel plot was used to test for publication bias.
All included studies had across-sectional study design. The association between
exposure to waste and positive serology for the HBV surface antigen (HBsAg)
showed a significant association [odds ratio (OR) 1.89, 95% confidence interval
(CI) 1.27-2.86; p = 0.0019]. The prevalence rates of HBsAg and anti-HBc
seropositivity was 0.04 (95% CI 0.03-0.05) and 0.21 (95% CI 0.14-0.28),
respectively (p <0.0001). We found no evidence of publication bias. The results
of this meta-analysis indicate a statistically significant association between
exposure to solid waste, whether healthcare or domestic, and positive HBV
infection markers. Therefore, the working conditions of waste collectors should
be analyzed more closely. Immunization against HBV is recommended as the chief
preventive measure for all solid waste workers.
PMID- 29340452
TI - Detection of multidrug-resistant Pseudomonas aeruginosa harboring bla GES-1 and
bla GES-11 in Recife, Brazil.
AB - INTRODUCTION: Pseudomonas aeruginosa, an important pathogen globally, presents
several resistance mechanisms. This study aimed to investigate the presence of
bla GES in clinical isolates of Pseudomonas aeruginosa obtained from various
clinical specimens from patients admitted to three different hospitals in Recife,
Brazil. The Guiana extended spectrum beta-lactamase (GES) enzymes are responsible
for conferring broad spectrum resistance to beta-lactam drugs, including the
carbapenems. METHODS: A total of 100 carbapenem-resistant P. aeruginosa isolates
underwent polymerase chain reaction (PCR) testing to identify bla GES, bla KPC,
bla SPM-1, bla IMP, and bla VIM. Additionally, PCR products positive for bla GES
were sequenced. The clonal profiles of these same isolates were then determined
by means of enterobacterial repetitive intergenic consensus (ERIC)-PCR analysis.
RESULTS: PCR analysis revealed that four isolates harbored bla GES; DNA
sequencing showed that two harbored bla GES-1 and two bla GES-11. Beta-lactamase
genes bla SPM-1, bla IMP, bla VIM, and bla KPC were investigated; none of these
genes was detected. Automated susceptibility testing methods (Vitek(r)2,
bioMerieux) showed that the bla GES-1-positive isolates were only susceptible to
polymyxin B. The patterns obtained with ERIC-PCR methods showed clonal
relationship between the two isolates that harbored bla GES-11, whereas different
clonal profiles were found in the isolates harboring bla GES-1. CONCLUSIONS: We
detected the presence of bacterial isolates positive for two different variants
of the enzyme GES in three different hospitals from Recife, Brazil. These enzymes
have a great capacity for dissemination among Gram-negative bacteria and confer
broad-spectrum resistance to beta-lactam antibiotics and to the carbapenems.
PMID- 29340453
TI - Seroprevalence and spatial distribution dynamics of Yersinia pestis antibodies in
dogs and cats from plague foci in the State of Ceara, Northeastern Brazil.
AB - INTRODUCTION: In Brazil, the plague is established in several foci located mainly
in the northeastern part of the country, where it alternates between active and
quiescent periods. These foci in the State of Ceara have high epidemiological
importance. In addition to other plague detection activities, plague areas can be
monitored through serological surveys of dogs and cats (domestic carnivores),
which, following feeding on plague-infected rodents, can develop mild to severe
forms of the disease and produce long-lasting antibodies. This study aimed to
characterize the circulation dynamics and spatial distribution of Yersinia pestis
antibodies in dogs and cats in plague foci areas of Ceara. METHODS: An ecological
study was conducted to analyze the temporal series and spatial distribution of
secondary data obtained from domestic carnivore serum surveillance in Ceara's
plague areas from 1990 to 2014. RESULTS: Joinpoint analysis revealed that the
overall trend was a reduction in antibody-positive animals. The mean proportion
of antibody-positivity during the whole study period was 1.5% (3,023/203,311) for
dogs, and 0.7% (426/61,135) for cats, with more than 4% antibody-positivity in
dogs in 1997 and 2002. Antibody titers ranging from 1/16 to 1/64 were frequent.
Despite fluctuations and a significant reduction, in recent years, there were
antibody-positive animals annually throughout the study period, and the
localities containing antibody-positive animals increased in number. CONCLUSION:
Yersinia pestis is actively circulating in the study areas, posing a danger to
the human population.
PMID- 29340454
TI - Human leptospirosis in the Federal District, Brazil, 2011-2015: eco
epidemiological characterization.
AB - INTRODUCTION: Leptospirosis is an infectious disease that affects more than 5,000
people per year in Brazil. The Federal District (FD) lacks epidemiological
studies of human leptospirosis and presents concerning rates of this disease,
especially considering its lethality. METHODS: Seventy-nine autochthonous human
cases of leptospirosis between 2011 and 2015 were analyzed, with the probable
infection location serving as a basis for the collection and analysis of the
environmental and epidemiological variables. RESULTS: The incidence of the
disease ranged from 0.68-13.39 per 100,000 inhabitants in 21 of the 31
administrative regions that compose the FD. The local profile of human
leptospirosis was predominantly associated with urban areas during the rainy
season, population access to the sewage network, the treated water network, and
the public garbage collection service. The vast majority of cases had a strong
association with synanthropic rodents at the infection sites. CONCLUSIONS: In
order to prevent and control potentially lethal human leptospirosis infection,
the eco-epidemiological characterization of this disease is a valuable tool for
public policies of prevention, control, and surveillance. In addition to
population awareness, the systematized control of synanthropic rodents could be
the main health action to reduce the incidence of this disease in the FD.
PMID- 29340455
TI - Central venous catheter-related infections in patients receiving short-term
hemodialysis therapy: incidence, associated factors, and microbiological aspects.
AB - INTRODUCTION: Bloodstream infections are the second most common cause of death
among patients on hemodialysis. This study aimed to evaluate the incidence of and
risk factors associated with central venous catheter-related infections in
patients undergoing hemodialysis, and to identify and characterize the type and
antimicrobial susceptibility profiles of the primary microorganisms isolated
during one year of follow-up. METHODS: A prospective cohort study was conducted
in 2014 in a hemodialysis referral center. We included 200 outpatients with acute
kidney injury who had no permanent venous access. A nurse assessed the patients
for signs of infection three times per week during dressing changes. The
clinicopathologic characteristics of patients with and without local or systemic
infection were compared. RESULTS: Fifty-five episodes of catheter-related
infections occurred in 43 (22%) patients; 38 (69%) were bloodstream infections
and 17 (31%) were local infections. Thirty-two (75%) patients with infection had
femoral vein catheter placement. In total, 6,240 hemodialysis sessions were
performed; the rates of primary bloodstream and local infection were 6.1 and 2.7
episodes per 1,000 patients on daily dialysis, respectively. In the univariate
analysis, diabetes was significantly associated with the development of
infection, while level of education, ethnicity, age, and sex were not. Gram
negative bacteria were primarily isolated from blood culture specimens (55% of
samples). Of the Gram-negative isolates, 56% were resistant to the carbapenems.
CONCLUSIONS: We identified a high incidence of catheter-related infections caused
by resistant microorganisms in patients undergoing hemodialysis via central
venous catheters.
PMID- 29340456
TI - New strategy to improve quality control of Montenegro skin test at the production
level.
AB - INTRODUCTION: The production of the Montenegro antigen for skin test poses
difficulties regarding quality control. Here, we propose that certain animal
models reproducing a similar immune response to humans may be used in the quality
control of Montenegro antigen production. METHODS: Fifteen Cavia porcellus
(guinea pigs) were immunized with Leishmania amazonensis or Leishmania
braziliensis , and, after 30 days, they were skin tested with standard Montenegro
antigen. To validate C. porcellus as an animal model for skin tests, eighteen
Mesocricetus auratus (hamsters) were infected with L. amazonensis or L.
braziliensis , and, after 45 days, they were skin tested with standard Montenegro
antigen. RESULTS: Cavia porcellus immunized with L. amazonensis or L.
braziliensis , and hamsters infected with the same species presented induration
reactions when skin tested with standard Montenegro antigen 48-72h after the
test. CONCLUSIONS: The comparison between immunization methods and immune
response from the two animal species validated C. porcellus as a good model for
Montenegro skin test, and the model showed strong potential as an in vivo model
in the quality control of the production of Montenegro antigen.
PMID- 29340457
TI - Diet Quality of patients with chronic Chagas disease in a tertiary hospital: a
case-control study.
AB - INTRODUCTION: Nutritional status has been implicated in the modulation of the
immune response, possibly augmenting the pathogenesis of Chagas disease (Cd). We
evaluated diet quality and nutritional status in adults and elderly patients with
chronic Cd in a tertiary hospital. METHODS: A case-control study of Cd patients
was conducted, paired for gender, age, and co-morbidities with non-Cd patients.
Anthropometric measurements and food frequency questionnaire was used, and diet
quality was assessed by the Brazilian Healthy Eating Index-Revised (BHEI-R). The
Estimated Average Requirement cut-off points were used to determine the dietary
micronutrient adequacy. The Cd group was further grouped according to Los Andes
classification. RESULTS: The study participants were 67 +/- 10 years old, 73.6%
elderly and 63% female. The prevalence of overweight/obesity and abdominal fat
was high in both groups; however, Cd group showed a lower prevalence of obesity
and increased risk of disease according to waist circumference classification.
There was no difference in BHEI-R score between groups (p=0.145). The Cd group
had sodium and saturated fat intake above recommendations and low intake of
unsaturated fat, vitamin D, E, selenium, magnesium, and dairy products; but
higher intake of iron. According to Los Andes classification, group III presented
lower intake of whole fruit and dietary fiber. CONCLUSIONS: Patients with Cd were
overweight and the quality of their diet was unsatisfactory based on the
recommended diet components for age and sex.
PMID- 29340458
TI - Morbidity of schistosomiasis mansoni in a low endemic setting in Ouro Preto,
Minas Gerais, Brazil.
AB - INTRODUCTION: Despite the advances of disease control programs, severe forms of
schistosomiasis are prevalent. The prevalence of the disease in areas frequented
by tourists urges for permanent prevention and control. The aim of this study was
to describe the morbidity of schistosomiasis in the district of Antonio Pereira,
Ouro Preto, Minas Gerais, Brazil. METHODS: The proportion of positives was
defined by Kato-Katz coproscopy and urinary POC-CCA rapid test. Hepatosplenic
form was diagnosed using abdominal ultrasound. RESULTS: Out of 180
participants,97 were examined by Kato-Katz, with 4 (4.1%) being positive. Thirty
four (22.1%) out of 154 were positive by POC-CCA. Five (2.8%) of 177 examined by
ultrasound had hepatosplenic form. One of them had undergone splenectomy. One
(0.6%)participant had myeloradiculopathy. CONCLUSIONS: Severe forms of
schistosomiasis are still prevalent in low endemic areas and should be thoroughly
investigated.
PMID- 29340459
TI - Ectopic forms of schistosomiasis mansoni in the second macroregion of Alagoas:
case series report and review of the literature.
AB - INTRODUCTION: Ectopic forms of schistosomiasis are those in which the parasitic
element is localized outside the portal system, the natural habitat of the
helminth. Although the prevalence rates of schistosomiasis are high in Brazil,
clinical and epidemiological data on ectopic forms of the disease are still
scarce. METHODS: Cross-sectional, retrospective and descriptive epidemiological
study in which cases with a confirmed histopathological diagnosis of an ectopic
form of schistosomiasis were analyzed. The cases were selected from a database of
the anatomic pathology files of a referral center. RESULTS: Of the 21 cases
identified, seven affected the female genital tract and five the male genital
tract; four cases were identified in the peritoneum; two cases involved lymph
nodes and two involved adipose tissue; and renal involvement was detected in one
case. CONCLUSIONS: The lack of knowledge of the clinical presentation of ectopic
forms of schistosomiasis makes the early identification and treatment of this
form difficult, with direct implications in the reduction of morbidity and
mortality in endemic areas.
PMID- 29340460
TI - First serologic evidence of human hantavirus infection in Alagoas State in
Northeastern Brazil.
AB - INTRODUCTION: Hantavirus cardiopulmonary syndrome (HCPS) is rare in Northeastern
Brazil. METHODS: Prospective surveillance was conducted over a two-year period in
Alagoas State, Northeastern Brazil. The prevalence of anti-hantavirus N-antigen
IgM and IgG in human serum samples was determined by enzyme-linked immunosorbent
assay testing. RESULTS: High avidity IgG was found in nine of 476 serum samples
tested (from 102 patients with clinical manifestations compatible with HCPS, 124
patients with leptospirosis, and 250 healthy rural workers). CONCLUSIONS:
Serologic evidence of past hantavirus infection in residents of Alagoas State
indicates that hantaviruses are present in northeastern Brazil, even in areas
silent for HCPS.
PMID- 29340461
TI - Synanthropic triatomines as potential vectors of Trypanosoma cruzi in Central
Brazil.
AB - INTRODUCTION: Chagas disease surveillance requires current knowledge on
synanthropic triatomines. We analyzed the occurrence and Trypanosoma cruzi
infection rates of triatomine bugs in central Brazil, during 2012-2014. METHODS:
Triatomines were collected inside or around houses, and T. cruzi infection was
determined by optical microscopy and conventional/quantitative polymerase chain
reaction. RESULTS: Of the 2706 triatomines collected, Triatoma sordida was the
most frequent species in Goias State, whereas Panstrongylus megistus predominated
in the Federal District. Parasites identified were T. cruzi, T. rangeli, and
Blastocrithidia sp. CONCLUSIONS: P. megistus and T. sordida sustained the risk of
T. cruzi transmission to humans in central Brazil.
PMID- 29340462
TI - Rhodnius stali: new vector infected by Trypanosoma rangeli (Kinetoplastida,
Trypanosomatidae).
AB - INTRODUCTION: Rhodnius stali infection by Trypanosoma rangeli is reported in this
study for the first time. METHODS: The triatomines were collected from the campus
of the Federal University of Acre in Rio Branco, Acre, Brazil. The identification
of T. rangeli was confirmed by multiplex polymerase chain reaction. RESULTS: The
examinations of two specimens revealed R. stali infection by the epimastigote
forms of T. rangeli. CONCLUSIONS: The encounter of R. stali infected by T.
rangeli generates an alert for the state of Acre, since the simultaneous presence
with Trypanosoma cruzi can make the differential diagnosis of Chagas disease
difficult.
PMID- 29340463
TI - Prevalence of and risk factors associated with the presence of Staphylococcus
aureus in the chronic wounds of patients treated in primary health care settings
in Brazil.
AB - INTRODUCTION: Wounds can be colonized by methicillin-resistant Staphylococcus
aureus (MRSA). METHODS: We evaluated the prevalence of S. aureus and MRSA in the
wounds of patients treated at Basic Health Units in Brazil and identified risk
factors associated with their presence. RESULTS: The prevalence rates of S.
aureus and MRSA were 51.5% and 8.7%, respectively. There was a correlation
between the presence of S. aureus in wounds and nostrils (p<0.01). A positive
association was detected between S. aureus infection and previous
benzylpenicillin use (p=0.02). No associations were observed for MRSA.
CONCLUSIONS: Multidrug-resistant pathogens are present in primary healthcare
settings in Brazil.
PMID- 29340464
TI - Seroprevalence of human Trypanosoma cruzi infection in the North of Estado de
Mexico.
AB - INTRODUCTION: Chagas disease is a neglected public health problem in Mexico;
however, detailed studies to determine the seroprevalence in some states have not
been performed. METHODS: A total 1,504 human serum from thirteen communities in
Estado de Mexico, were analyzed with three diagnostics techniques. RESULTS: The
overall seroprevalence was 9.1%, with high prevalence among people aged 51-60
years, while people aged 0-29 years were seronegative against T. cruzi.
CONCLUSIONS: Our data demonstrated the seroprevalence of T. cruzi in the North of
the Estado de Mexico, an area considered as non-endemic; however, epidemiological
conditions necessary for natural transmission were found.
PMID- 29340465
TI - Variability in the clinical distributions of Candida species and the emergence of
azole-resistant non-Candida albicans species in public hospitals in the Midwest
region of Brazil.
AB - INTRODUCTION: Incidence and antifungal susceptibility of Candida spp. from two
teaching public hospitals are described. METHODS: The minimum inhibitory
concentrations of fluconazole, voriconazole, itraconazole, and amphotericin B
were determined using Clinical Laboratory Standard Institute broth microdilution
and genomic differentiation using PCR. RESULTS: Of 221 Candida isolates, 50.2%
were obtained from intensive care unit patients; 71.5% were recovered from urine
and 9.1% from bloodstream samples. Candida parapsilosis sensu stricto was the
most common candidemia agent. CONCLUSIONS: We observed variations in Candida
species distribution in hospitals in the same geographic region and documented
the emergence of non-C. albicans species resistant to azoles.
PMID- 29340466
TI - Schistosomiasis in the Amazon region: is the current diagnostic strategy still
appropriate?
AB - INTRODUCTION: This study analyzed the performance of the Kato Katz technique in
detecting intestinal schistosomiasis in the State of Para. METHODS: Of three
stool samples provided by each of 380 participants, a total of 16 Kato Katz
slides were examined to define the reference value (RV) of positives for
comparisons. RESULTS: The RV revealed 37 (9.7%) infected participants in contrast
to 10 (2.6%) according to a single slide. CONCLUSIONS: This significant
underestimation of the infection rate gives reason to discuss if the current
classification of prevalence levels reflects the real situation, principally in
low transmission areas, like the Amazon region.
PMID- 29340467
TI - Prevalence of and risk factors for intestinal parasite infections in pediatric
patients admitted to public hospitals in Southern Brazil.
AB - INTRODUCTION: This study aimed to evaluate the prevalence of intestinal
parasitosis and to identify risk factors associated therewith in hospitalized
children. METHODS: Three fecal samples from each patient were evaluated using
three different techniques. The patients' nutritional and socioeconomic status
and hematologic profiles were evaluated. RESULTS: Of 106 children, 32.1% tested
positive for intestinal parasitosis. The associated risk factors were low
parental education levels and children's nail-biting habit. Eosinophilia,
observed in 15 cases, was not associated with parasitosis. CONCLUSIONS: We
recommend routine fecal parasitologic examination for hospitalized children and
implementation of educational campaigns on the prevention of these diseases.
PMID- 29340468
TI - Serosurvey of Leptospira spp. and Toxoplasma gondii in rats captured from two
zoos in Southern Brazil.
AB - INTRODUCTION: Norway rats (Rattus norvegicus) are zoonotic reservoirs for
Leptospira spp. and Toxoplasma gondii, and influence diseases in urban areas.
METHODS: Free-ranging and laboratory-raised rats from two zoos in southern Brazil
were tested for Leptospira spp. and T. gondii using microscopic agglutination and
modified agglutination tests, respectively. RESULTS: Overall, 25.6% and 4.6% free
ranging rats tested positive for Leptospira spp. and T. gondii, respectively,
with co-seropositivity occurring in two animals. For laboratory-raised rats, 20%
tested positive for Leptospira spp. Also, Leptospira biflexa serovar Patoc and
Leptospira noguchii serovar Panama were found. CONCLUSIONS: Serosurveys can show
the environmental prevalence of zoonotic pathogens.
PMID- 29340469
TI - Sofosbuvir and daclatasvir combination therapy for current hepatitis C virus
genotype 4 achieves SVR: a case report of HCV genotype 4 from the Amazon.
AB - Hepatitis C is a worldwide endemic disease. However, hepatitis C virus genotype 4
(HCV GT-4) has rarely been reported in Brazil. HCV GT-4 demonstrates high
sustained virological response (SVR). Here, we report the case of a 62-year-old
HCV GT-4 positive woman complaining of a headache, nausea, and arthralgia. The
patient was treated according to the protocol for genotype 4 (12 weeks
administration of 400mg sofosbuvir and 60mg daclatasvir daily) and achieved SVR.
Although this is not an Amazonas autochthonous case, the presence of genotype 4
is rarely reported in the region.
PMID- 29340470
TI - Traumatic rupture of liver hydatid cysts into the peritoneal cavity of an 11-year
old boy: a case report from Iran.
AB - This is the first published case report of an 11-year-old patient with a rupture
of a liver hydatid cyst (HC) into the peritoneal cavity after an abdominal trauma
in Iran. The disease was diagnosed using focused abdominal sonography for trauma.
To date, no cases of traumatic ruptures of liver HCs in children have been
reported in Iran. In the endemic regions of the world, where patients suffer from
a history of trauma and constant abdominal symptoms or anaphylactic shock, early
diagnosis of HC is crucial as it may disseminate to other organs. The condition
needs conservative surgery and follow-up.
PMID- 29340471
TI - Epididymo-orchitis caused by Histoplasma capsulatumin a Colombian patient.
AB - Although histoplasmosis is generally a self-limited disease, disseminated
infection can occur in patients lacking effective cell-mediated immunity,
reaching virtually every organ, even the genitourinary tract in rare cases. We
report a case of epididymo-orchitis in an immunocompetent 38-year-old bricklayer
from the rural area of Villeta, Cundinamarca, Colombia. The patient presented
with testicular pain and macroscopic scrotal changes requiring a left
orchiectomy, with microbiological isolation and molecular confirmation of
Histoplasma capsulatum.
PMID- 29340472
TI - Disseminated cutaneous sporotrichosis in patient with alcoholism.
AB - Sporotrichosis is the most prevalent subcutaneous mycosis and is characterized by
a subacute or chronic development of a cutaneous or subcutaneous nodular lesion.
It is caused by the dimorphic fungus Sporothrix spp, which may manifest in
different clinical forms. The disseminated cutaneous form is uncommon and is more
likely to occur in immunocompromised patients. We report a 47-year-old male
patient with multiple cutaneous and subcutaneous nodules. The patient was
diagnosed with disseminated cutaneous sporotrichosis based on the isolation and
identification of Sporothrix spp. The patient was treated with potassium iodide,
which resulted in clinical improvement of the lesions.
PMID- 29340473
TI - A case of brucellar spondylitis with lumbar spondylolisthesis.
PMID- 29340474
TI - Cryptococcosis in a transplanted kidney allograft.
PMID- 29340476
TI - Erratum.
AB - [This corrects the article doi: 10.1590/0037-8682-0258-2017].
PMID- 29340475
TI - A proposal for the use of standardized abbreviations for the genera of triatomine
bugs (Reduviidae: Triatominae) across the World.
PMID- 29340477
TI - Occurrence of gastrointestinal parasites in wild animals in State of Parana,
Brazil.
AB - The objective of this study was to determine the prevalence and diversity of
gastrointestinal parasites in fecal samples from wild birds and mammals from the
State of Parana. In total, 220 stool samples were sent to Parasitic Diseases
Laboratory of the Federal University of Parana during 13 months (Jan/2013
Jan/2014). A total of 52.7% (116/220) of the animals were positive for cysts,
oocysts, eggs and/or trophozoites. In birds, the positivity rate was 37.9%
(25/66) and mammals was 59.1% (91/154). Strongyloidea superfamily eggs were
observed in 37.3% (82/220) of the samples, Eimeria spp. in 10% (22/220), and
Trichuris spp. in 4.5% (10/220). The most frequent mammal species were llamas
(Lama glama), and dromedaries (Camelus bactrianus) with infection rate of 70.1%
(54/77) and 60.8% (14/23), respectively. In other hand, cockatiels (Nymphicus
hollandicus) and ring necks (Psittacula krameri), were the most researched birds,
with infection rate of 20% (40/50) and 100% (6/6), respectively. A high
prevalence of gastrointestinal parasites was observed in most of wildlife
animals. Further investigations should be conducted focusing on parasite control
strategies and the conservation measurements for harmonizing the human-animal
interaction on the long-term, reducing associated health risks.
PMID- 29340478
TI - The long and successful journey of electrochemically active amino acids. From
fundamental adsorption studies to potential surface engineering tools.
AB - Proteins have been the subject of electrochemical studies. It is possible to
apply electrochemical techniques to obtain information about their structure due
to the presence of five electroactive amino acids that can be oriented to the
outside of the peptidic chain. These amino acids are L-Tryptophan (L-Trp), L
Tyrosine (L-Tyr), L-Histidine (L-His), L-Methionine (L-Met) and L-Cysteine (L
Cys); their electrochemical behavior being subject of extensive research, but it
is still controversial. No spectroscopic investigations have been reported on L
Trp, and due to the short life time of the intermediates, ex situ techniques
cannot be employed, leading to a never-ending discussion about possible
intermediates. In the L-Tyr and L-His cases, spectroelectrochemical studies were
performed and different intermediates were observed, suggesting that some
intermediates may be observed under specific conditions, as proposed for L-Cys.
This amino acid is the most interesting among the electroactive ones because of
the presence of a thiol moiety at its side chain, leading to a wide range of
oxidation states. It can adsorb onto surfaces of different crystallographic
orientation in stereoselective conformation, modifying the surface for different
applications.as a surface engineering tool since it plays the role of as an
anchor for the growing of nanocrystals inside proteic templates.
PMID- 29340479
TI - Enzymes immobilized in Langmuir-Blodgett films: Why determining the surface
properties in Langmuir monolayer is important?
AB - In this review we discuss about the immobilization of enzymes in Langmuir
Blodgett films in order to determine the catalytic properties of these
biomacromolecules when adsorbed on solid supports. Usually, the conformation of
enzymes depends on the environmental conditions imposed to them, including the
chemical composition of the matrix, and the morphology and thickness of the film.
In this review, we show an outline of manuscripts that report the immobilization
of enzymes as LB films since the 1980's, and also some examples of how the
surface properties of the floating monolayer prepared previously to the transfer
to the solid support are important to determine the efficiency of the resulting
device.
PMID- 29340480
TI - Bone repair access of BoneCeramicTM in 5-mm defects: study on rat calvaria.
AB - OBJECTIVE: The aim of this study was to evaluate the osteoconductive potential of
BoneCeramicTM on bone healing in rat calvaria 5-mm defects. MATERIAL AND METHODS:
A 5-mm calvaria bone defect was induced in three groups and the defect was not
filled with biomaterial [Clot Group (CG)], autogenous bone (AG), or Bone Ceramic
Group (BCG). Animals were euthanized after 14 or 28 days and the bone tissue
within the central area of the bone defect was evaluated. Results were compared
using ANOVA and Tukey test (p<0.05). Immunohistochemistry was performed using
primary antibodies against osteocalcin, RUNX-2, TRAP, VEGF proteins, and 3
dimensional images of the defects in MUCT were obtained to calculate bone mineral
density (BMD). RESULTS: In BCG, the defect was completely filled with biomaterial
and new bone formation, which was statistically superior to that in the GC group,
at both time-points (p<0.001 for 14 days; p=0.002 for 28 days). TRAP protein
showed weak, RUNX-2 showed a greater immunolabeling when compared with other
groups, VEGF showed moderate immunostaining, while osteocalcin was present at all
time-points analyzed. The MUCT images showed filling defect by BCG (BMD= 1337 HU
at 28 days). CONCLUSION: Therefore, the biomaterial tested was found to be
favorable to fill bone defects for the reporting period analyzed.
PMID- 29340481
TI - Evaluation of the sealing ability of different root canal sealers: a combined SEM
and micro-CT study.
AB - OBJECTIVE: The purpose of this study was to analyze the ability of multiple
compounds to seal the dental tubules using scanning electron microscopy (SEM) and
micro-computed tomogra-phy (micro-CT). MATERIAL AND METHODS: Twenty-four single
root human mandibular premolars were selected and instrumented with nickel
titanium rotary file and the final file size was #40/06. They were then randomly
allocated into 2 groups, and all samples were filled with single cone gutta
percha (#40/06) and one of the tested sealers (AH Plus and EndoSequence BC
sealers). All specimens were scanned using micro-CT and then three from each
group were randomly selected for SEM analysis. RESULTS: According to SEM, both
root canal sealers showed sufficient adaptation to dentin along the whole length
of the root canal, though the coronal sections presented superior sealing than
the apical sections. Micro porosity analyses revealed that the volume of closed
pores and the surface of closed pores had the largest values in the coronal
sections, followed by the middle and the apical sections for both sealants
(p<0.05). However, no significant difference was observed for those two
parameters between AH Plus and EndoSequence BC sealers in any of the three
sections (p>0.05), whereas they were larger in the apical section when the AH
Plus sealer was used. CONCLUSIONS: By using the single cone technique, neither
EndoSequence or AH Plus pro-vides a porosity-free root canal filling. The
EndoSequence BC sealer may have similar sealing abilities regarding the whole
root canal as the AH Plus sealer. A better sealing effect could be obtained in
the coronal and middle sections of a root canal than the apical part by using the
tested sealers.
PMID- 29340482
TI - Clear cell odontogenic carcinoma of the mandible: a treatment strategy.
AB - Clear cell odontogenic carcinoma (CCOC) is a rare odontogenic tumor of the jaws,
histologically characterized by the presence of agglomerates of cells with
eosinophilic cytoplasm. The patient, a 62-year-old Caucasian woman, presented an
intraosseous lesion in the mandibular symphysis. A clinical examination revealed
a discrete volumetric increase with a hard consistency, palpable to extraoral and
intraoral examinations. Imaging studies revealed an extensive radiolucent area,
without defined limits, extending from the region of the right second premolar to
the left canine. Incisional biopsy analysis indicated a diagnosis of CCOC. The
treatment proposed was segmental resection of the mandible with a safety margin.
After six months without recurrence, definitive mandibular reconstruction was
performed using an iliac crest graft, followed by rehabilitation with implant
supported denture after five months. After three years of post-resection follow
up, the patient has shown no evidence of recurrence or metastasis. She continues
to be under follow-up. To conclude, CCOC must be considered a malignant tumor
with aggressive behavior. Previous studies have shown that resection with free
margins is a treatment with a lower rate of recurrence. Nevertheless, long-term
follow-up is necessary for such patients.
PMID- 29340483
TI - Idiopathic pulmonary fibrosis in Brazil: challenges for epidemiological
characterization and management.
PMID- 29340484
TI - Evolution in the management of non-small cell lung cancer in Brazil.
PMID- 29340486
TI - Tree-in-bud pattern.
PMID- 29340485
TI - Noninvasive positive airway pressure: from critically ill patients to physical
exercise in outpatients.
PMID- 29340487
TI - Understanding diagnostic tests. Part 2.
PMID- 29340488
TI - Impact of continuous positive airway pressure on the pulmonary changes promoted
by immersion in water.
AB - OBJECTIVE: To determine whether different levels of CPAP improve the lung volumes
and capacities of healthy subjects immersed in water. METHODS: This was a
randomized clinical trial, conducted between April and June of 2016, involving
healthy female volunteers who were using oral contraceptives. Three 20-min
immersion protocols were applied: control (no CPAP); CPAP5 (CPAP at 5 cmH2O); and
CPAP10 (CPAP at 10 cmH2O). We evaluated HR, SpO2, FVC, FEV1, the FEV1/FVC ratio,
peak expiratory flow rate (PEFR), and FEF25-75%) at three time points: pre
immersion; 10 min after immersion; and 10 min after the end of each protocol.
RESULTS: We evaluated 13 healthy volunteers. The CPAP10 protocol reversed the
restrictive pattern of lung function induced by immersion in water, maintaining
pulmonary volumes and capacities for a longer period than did the CPAP5 protocol.
CONCLUSIONS: When the hemodynamic change causing a persistent lung disorder, only
the application of higher positive pressures is effective in maintaining long
term improvements in the pulmonary profile.
PMID- 29340489
TI - Tuberculosis infection among primary health care workers.
AB - OBJECTIVE: To estimate the prevalence of and determine the risk factors
associated with latent Mycobacterium tuberculosis infection (LTBI) among primary
health care workers in the city of Vitoria, Brazil. METHODS: This was a cross
sectional study with data collected through a survey regarding socio-demographic,
occupational, clinical, and exposure characteristics, as well as knowledge about
tuberculosis, conducted between 2011 and 2012. All participants underwent a
tuberculin skin test (TST), and TSTs were read at 72 h by a trained professional.
RESULTS: A total of 218 primary health care workers participated in the study.
The prevalence of TST positivity at the >= 10-mm and >= 5-mm cut-off points was,
respectively, 39.4% (95% CI: 32.9-45.9) and 54.1% (95% CI: 47.4-60.7). Regarding
occupational categories, community health agents had the highest proportion of
TST positivity, regardless of the cut-off point (>= 10 mm: 47.5%; and >= 5 mm:
60.5%). Regarding factors associated with TST results, "having had a previous
TST" showed a statistically significant association with TST positivity at the >=
10-mm and >= 5-mm cut-off points (OR = 2.5 [95% CI: 1.17-5.30] and OR = 2.18 [95%
CI: 1.23-3.87], respectively). CONCLUSIONS: The prevalence of LTBI was found to
be high among the primary health care workers in this sample. Therefore, we
recommend the establishment of a periodic screening program for LTBI and
implementation of effective biosafety policies for the prevention of this
infection among primary health care workers.
PMID- 29340490
TI - Accuracy of closed pleural biopsy in the diagnosis of malignant pleural effusion.
AB - OBJECTIVE: Previous studies have demonstrated that closed pleural biopsy (CPB)
has a sensitivity of less than 60% for diagnosing malignancy. Therefore,
controversy has recently emerged regarding the value of CPB as a diagnostic test.
Our objective was to assess the accuracy of CPB in diagnosing malignancy in
patients with pleural effusion. METHODS: This was a prospective 8-year study of
individuals who underwent CPB to establish the etiology of pleural effusion.
Information on each patient was obtained from anatomopathological reports and
medical records. When CPB findings showed malignancy or tuberculosis, the biopsy
was considered diagnostic, and that was the definitive diagnosis. In cases in
which biopsy histopathological findings were nonspecific, a definitive diagnosis
was established on the basis of other diagnostic procedures, such as
thoracoscopy, thoracotomy, fiberoptic bronchoscopy, biochemical and cellular
measurements in pleural fluid, and/or microbiological tests. The accuracy of CPB
was determined with 2 * 2 contingency tables. RESULTS: A total of 1034 biopsies
from patients with pleural effusion were studied. Of those, 171 (16.54%) were
excluded from the accuracy analysis either because of inadequate samples or
insufficient information. The results of the accuracy analysis were as follows:
sensitivity, 77%; specificity, 98%; positive predictive value, 99%; negative
predictive value, 66%; positive likelihood ratio, 38.5; negative likelihood
ratio, 0.23; pre-test probability, 2.13; and post-test probability, 82.
CONCLUSIONS: CPB is useful in clinical practice as a diagnostic test, because
there is an important change from pre-test to post-test probability.
PMID- 29340491
TI - Survival in a cohort of patients with lung cancer: the role of age and gender in
prognosis.
AB - OBJECTIVE: To determine the demographic and clinical characteristics of patients
with non-small cell lung cancer (NSCLC), as well as their disease course, by age
group and gender. METHODS: This was a retrospective cohort study of patients
diagnosed with NSCLC from 2000 to 2012 and followed until July 2015 in a tertiary
referral hospital in the city of Sao Paulo, Brazil. Based on the 25th and 75th
percentiles of the age distribution, patients were stratified into three age
groups: < 55 years; >= 55 and < 72 years; and >= 72 years. Survival time was
evaluated during the follow-up period of the study. Functions of overall and
gender-specific survival stratified by age groups (event: all-cause mortality)
were calculated using the Kaplan-Meier method. Differences among survival curves
were assessed via the log-rank test. RESULTS: We included 790 patients with the
following age distribution: < 55 years, 165 patients; >= 55 and < 72 years, 423;
and >= 72 years, 202. In the entire sample, there were 493 men (62.4%).
Adenocarcinoma was the most common histological pattern in the < 72-year age
groups; 575 patients (73%) presented with advanced disease (stages IIIB-IV). The
median 5-year survival was 12 months (95% CI: 4-46 months), with no significant
differences among the age groups studied. CONCLUSIONS: NSCLC remains more common
in men, although we found an increase in the proportion of the disease in women
in the < 55-year age group. Adenocarcinoma predominated in women. In men,
squamous cell carcinoma predominated in the >= 72-year age group. Most patients
presented with advanced-stage disease at diagnosis. There were no statistical
differences in survival between genders or among age groups.
PMID- 29340492
TI - Evaluation of the impact that the changes in tuberculosis treatment implemented
in Brazil in 2009 have had on disease control in the country.
AB - OBJECTIVE: To analyze the impact that the 2009 changes in tuberculosis treatment
in Brazil had on the rates of cure, tuberculosis recurrence, mortality, treatment
abandonment, and multidrug-resistant tuberculosis (MDR-TB). METHODS: An ordinary
least squares regression model was used in order to perform an interrupted time
series analysis of secondary data collected from the Brazilian Tuberculosis Case
Registry Database for the period between January of 2003 and December of 2014.
RESULTS: The 2009 changes in tuberculosis treatment in Brazil were found to have
no association with reductions in the total number of cases (beta = 2.17; 95% CI:
-3.80 to 8.14; p = 0.47) and in the number of new cases (beta = -0.97; 95% CI:
5.89 to 3.94; p = 0.70), as well as having no association with treatment
abandonment rates (beta = 0.40; 95% CI: -1.12 to 1.93; p = 0.60). The changes in
tuberculosis treatment also showed a trend toward an association with decreased
cure rates (beta = -4.14; 95% CI: -8.63 to 0.34; p = 0.07), as well as an
association with increased mortality from pulmonary tuberculosis (beta = 0.77;
95% CI: 0.16 to 1.38; p = 0.01). Although there was a significant increase in MDR
TB before and after the changes (p < 0.0001), there was no association between
the intervention (i.e., the changes in tuberculosis treatment) and the increase
in MDR-TB cases. CONCLUSIONS: The changes in tuberculosis treatment were unable
to contain the decrease in cure rates, the increase in treatment abandonment
rates, and the increase in MDR-TB rates, being associated with increased
mortality from pulmonary tuberculosis during the study period.Keywords:
Tuberculosis, pulmonary/epidemiology; Tuberculosis, pulmonary/drug therapy;
Tuberculosis, pulmonary/mortality; Interrupted time series analysis; Drug
resistance, multiple; Drug compounding.
PMID- 29340493
TI - Mortality from idiopathic pulmonary fibrosis: a temporal trend analysis in
Brazil, 1979-2014.
AB - OBJECTIVE: To analyze mortality from idiopathic pulmonary fibrosis (IPF) in
Brazil over the period 1979-2014. METHODS: Microdata were extracted from the
Brazilian National Ministry of Health Mortality Database. Only deaths for which
the underlying cause was coded as International Classification of Diseases
version 9 (ICD-9) 515 or 516.3 (until 1995) or as ICD version 10 (ICD-10) J84.1
(from 1996 onward) were included in our analysis. Standardized mortality rates
were calculated for the 2010 Brazilian population. The annual trend in mortality
rates was analyzed by joinpoint regression. We calculated risk ratios (RRs) by
age group, time period of death, and gender, using a person-years denominator.
RESULTS: A total of 32,092 deaths were recorded in the study period. Standardized
mortality rates trended upward, rising from 0.24/100,000 population in 1979 to
1.10/100,000 population in 2014. The annual upward trend in mortality rates had
two inflection points, in 1992 and 2008, separating three distinct time segments
with an annual growth of 2.2%, 6.8%, and 2.4%, respectively. The comparison of
RRs for the age groups, using the 50- to 54-year age group as a reference, and
for the study period, using 1979-1984 as a reference, were 16.14 (14.44-16.36)
and 6.71 (6.34-7.12), respectively. Men compared with women had higher
standardized mortality rates (per 100,000 person-years) in all age groups.
CONCLUSION: Brazilian IPF mortality rates are lower than those of other
countries, suggesting underdiagnosis or underreporting. The temporal trend is
similar to those reported in the literature and is not explained solely by
population aging.
PMID- 29340494
TI - Niemann-Pick disease type B: HRCT assessment of pulmonary involvement.
AB - OBJECTIVE: To analyze HRCT findings in patients with Niemann-Pick disease (NPD)
type B, in order to determine the frequency of HRCT patterns and their
distribution in the lung parenchyma, as well as the most common clinical
characteristics. METHODS: We studied 13 patients (3 males and 10 females) aged 5
to 56 years. HRCT images were independently evaluated by two observers, and
disagreements were resolved by consensus. The inclusion criteria were presence of
abnormal HRCT findings and diagnosis of NPD type B confirmed by histopathological
examination of a bone marrow, lung, or liver biopsy specimen. RESULTS: The most
common clinical findings were hepatosplenomegaly and mild to moderate dyspnea.
The most common HRCT patterns were smooth interlobular septal thickening and
ground-glass opacities, which were both present in all patients. Intralobular
lines were present in 12 patients (92.3%). A crazy-paving pattern was observed in
5 patients (38.4%), and areas of air trapping were identified in only 1 case
(7.6%). Pulmonary involvement was bilateral in all cases, with the most affected
area being the lower lung zone. CONCLUSIONS: Smooth interlobular septal
thickening, with or without associated ground-glass opacities, in patients with
hepatosplenomegaly is the most common finding in NPD type B.
PMID- 29340495
TI - Validation of the STOP-Bang questionnaire as a means of screening for obstructive
sleep apnea in adults in Brazil.
AB - OBJECTIVE: To validate the Portuguese-language version of the STOP-Bang (acronym
for Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index,
Age, Neck circumference, and Gender) questionnaire, culturally adapted for use in
Brazil, as a means of screening for obstructive sleep apnea (OSA) in adults.
METHODS: In this validation study, we enrolled patients >= 18 years of age,
recruited between May of 2015 and November of 2016. All patients completed the
STOP-Bang questionnaire and underwent overnight polysomnography. To evaluate the
performance of the questionnaire, we used contingency tables and areas under the
(receiver operating characteristic) curve (AUCs). RESULTS: We included 456
patients. The mean age was 43.7 +/- 12.5 years, and 291 (63.8%) of the patients
were male. On the basis of the apnea-hypopnea index (AHI), we categorized OSA as
mild/moderate/severe (any OSA; AHI >= 5 events/h), moderate/severe (AHI >= 15
events/h), or severe (AHI >= 30 events/h). The overall prevalence of OSA was
78.3%, compared with 52.0%, and 28.5% for moderate/severe and severe OSA,
respectively. The most common score on the STOP-Bang questionnaire was 4 points
(n = 106), followed by 3 points (n = 85) and 5 points (n = 82). An increase in
the score was paralleled by a reduction in sensitivity with a corresponding
increase in specificity for all AHI cut-off points. The AUCs obtained for the
identification of any, moderate/severe, and severe OSA were: 0.743, 0.731, and
0.779, respectively. For any OSA, the score on the questionnaire (cut-off, >= 3
points) presented sensitivity, specificity, and accuracy of 83.5%, 45.5%, and
75.2%, respectively. CONCLUSIONS: The STOP-Bang questionnaire performed
adequately for OSA screening, indicating that it could be used as an effective
screening tool for the disorder.
PMID- 29340496
TI - Effects of simple long-term respiratory care strategies in older men with COPD.
AB - OBJECTIVE: To evaluate a 24-month supervised, community-based maintenance
exercise program after 3 months of pulmonary rehabilitation (PR) in comparison
with a 27-month physical activity counseling program, in terms of the effects on
maximal muscle strength, muscle power output, and exercise capacity, in
individuals with COPD. METHODS: Sixty-three men with moderate-to-severe COPD were
recruited from two previous studies. Of those 63 participants, 31 were offered 3
months of PR followed by a 24-month supervised maintenance exercise program
(24MME group) and 32 were offered a 27-month physical activity counseling program
(27MPAC group). Measurements at 3 months and at the end of the study period
included maximal strength of the upper and lower limbs, power output of the lower
limbs, six-minute walk distance (6MWD), and quality of life. RESULTS: At 27
months, the improvements in maximal strength of the upper and lower limbs were
greater in the 24MME group than in the 27MPAC group (37.6 +/- 28.3% and 28.4 +/-
13.3%, respectively, vs. 8.8 +/- 16% and 13.6 +/- 16.4%, respectively; p < 0.05),
as was the improvement in power output of the lower limbs (24.6 +/- 18.4% vs.
2.3 +/- 28.5%; p < 0.01). The increase in the 6MWD after 3 months was also
greater in the 24MME group than in the 27MPAC group (33.2 +/- 36.6 m vs. 2.9 +/-
34.7 m; p < 0.05), although there were no differences between the two groups in
terms of the Delta6MWD at 27 months (vs. baseline). CONCLUSIONS: A supervised,
community-based maintenance program is a successful long-term strategy to
preserve the benefits of PR on peripheral muscle function and exercise capacity
in individuals with COPD. However, physical activity counseling can maintain
maximal muscle strength and exercise capacity in such individuals.
PMID- 29340498
TI - Omalizumab in patients with severe uncontrolled asthma: well-defined eligibility
criteria to promote asthma control.
PMID- 29340497
TI - Tuberculosis treatment.
AB - Tuberculosis treatment remains a challenge due to the need to consider, when
approaching it, the context of individual and collective health. In addition,
social and economic issues have been shown to be variables that need to be
considered when it comes to treatment effectiveness. We conducted a critical
review of the national and international literature on the treatment of
tuberculosis in recent years with the aims of presenting health care workers with
recommendations based on the situation in Brazil and better informing decision
making regarding tuberculosis patients so as to minimize morbidity and interrupt
disease transmission.
PMID- 29340499
TI - Primary sclerosing epithelioid fibrosarcoma of the pleura.
PMID- 29340500
TI - Respiratory evaluation through volumetric capnography among grade III obese and
eutrophic individuals: a comparative study.
AB - BACKGROUND: Excess trunk body fat in obese individuals influences respiratory
physiological function. The aims of this study were to compare volumetric
capnography findings (VCap) between severely obese patients and normal-weight
subjects and to assess whether there is any association between neck
circumference (NC), waist-hip ratio (WHR) and VCap among grade III obese
individuals. DESIGN AND SETTING: Analytical observational case-matched cross
sectional study, University of Campinas. METHODS: This cross-sectional study
compared VCap variables between 60 stage III obese patients and 60 normal-weight
individuals. RESULTS: In comparison with the normal-weight group, obese patients
presented higher alveolar minute volume (8.92 +/- 4.94 versus 6.09 +/- 2.2; P = <
0.0001), CO2 production (278 +/- 91.0 versus 209 +/- 60.23; P < 0.0001),
expiratory tidal volume (807 +/- 365 versus 624 +/- 202; P = 0.005), CO2
production per breath (21.1 +/- 9.7 versus 16.7 +/- 6.16; P = 0.010) and peak
expiratory flow (30.9 +/- 11.9 versus 25.5 +/- 9.13; P = 0.004). The end
expiratory CO2 (PetCO2) concentration (33.5 +/- 4.88 versus 35.9 +/- 3.79; P =
0.013) and the phase 3 slope were normalized according to expired tidal volume
(0.02 +/- 0.05 versus 0.03 +/- 0.01; P = 0.049) were lower in the obese group.
CONCLUSIONS: The greater the NC was, the larger were the alveolar minute volume,
anatomical dead space, CO2 production per minute and per breath and expiratory
volume; whereas the smaller were the phase 2 slope (P2Slp), phase 3 slope (P3Slp)
and pressure drop in the mouth during inspiration.
PMID- 29340501
TI - Accidents involving motorcycles and potential years of life lost. An ecological
and exploratory study.
AB - CONTEXT AND OBJECTIVE: Traffic accidents have gained prominence as one of the
modern epidemics that plague the world. The objective of this study was to
identify the spatial distribution of potential years of life lost (PYLL) due to
accidents involving motorcycles in the state of Sao Paulo, Brazil. DESIGN AND
SETTING: Ecological and exploratory study conducted in Sao Paulo. METHODS: Data
on deaths among individuals aged 20-39 years due to motorcycle accidents (V20-V29
in the International Classification of Diseases, 10th revision) in the state of
Sao Paulo in the years 2007-2011 were obtained from DATASUS. These data were
stratified into a database for the 63 microregions of this state, according to
where the motorcyclist lived. PYLL rates per 100,000 inhabitants were calculated.
Spatial autocorrelations were estimated using the Global Moran index (IM).
Thematic, Moran and Kernel maps were constructed using PYLL rates for the age
groups of 20-29 and 30-39 years. The Terraview 4.2.2 software was used for the
analysis. RESULTS: The PYLL rates were 486.9 for the ages of 20-29 years and
199.5 for 30-39 years. Seventeen microregions with high PYLL rates for the age
group of 20-29 years were identified. There was higher density of these rates on
the Kernel map of the southeastern region (covering the metropolitan region of
Sao Paulo). There were no spatial autocorrelations between rates. CONCLUSIONS:
The data presented in this study identified microregions with high accident rates
involving motorcycles and microregions that deserve special attention from
regional managers and traffic experts.
PMID- 29340502
TI - Recurrence of retroperitoneal localized perivascular epithelioid cell tumor two
years after initial diagnosis: case report.
AB - CONTEXT: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal
tumors. Adjuvant radiotherapy and/or chemotherapy are administered according to
the patient's clinical characteristics. CASE REPORT: A 42-year-old female patient
was operated to treat a retroperitoneal mass. The diagnosis was established as
PEComa with benign behavior. Two years after the diagnosis, chest and abdominal
computed tomography scans showed intra-abdominal recurrence and
lymphangioleiomyomatosis in the lung. Treatment with everolimus was started. The
disease stabilized in the third month of treatment, according to the response
evaluation criteria in solid tumors. CONCLUSION: PEComas are tumors with
unpredictable behavior. Therefore, these patients require long-term follow-up,
even in cases of correct diagnosis and benign PEComa.
PMID- 29340503
TI - Epidemiological situation of acquired immunodeficiency syndrome (AIDS)-related
mortality in a municipality in northeastern Brazil. A retrospective cross
sectional study.
AB - CONTEXT AND OBJECTIVE: The number of acquired immunodeficiency syndrome (AIDS)
related deaths covers different segments of the population differently, making
monitoring of this mortality essential. The aim of this study was to describe the
epidemiological situation of AIDS-related mortality in a municipality in the
northeastern region of Brazil. DESIGN AND SETTING: Retrospective cross-sectional
study based on data from death certificates in the mortality information system
of the Health Information Center, Municipal Health Foundation, Brazil. METHODS:
Between 2003 and 2013, we investigated death certificates on which AIDS-related
mortality was reported. Sociodemographic data, year, place, type of establishment
where death occurred and underlying and associated causes that led to AIDS
related death were described. The Mann-Kendall test was used to verify the growth
trend of the standardized mortality rate over the period studied. RESULTS: Among
the 1,066 AIDS-related deaths, 69.7% were among men; 47.2% of the individuals
were 28-41 years of age, 32.7% had had 4-7 years of schooling, 66.9% were pardos
(mixed race), 55.7% were unmarried and 15.3% were housekeepers. Hospitals were
the site of 97% of the deaths, and 91% occurred at public hospitals. Respiratory
failure was the main cause of death. The prevalence of infectious and parasitic
diseases was 99.0%. AIDS-related mortality increased by 160% over the period
studied, from 5.5/100,000 inhabitants in 2003 to 14.3/100,000 in 2013.
CONCLUSION: In the Brazilian municipality studied here, AIDS-related mortality
was most prevalent among men and young adults of lower socioeconomic level. Over
the period studied, the mortality rate increased.
PMID- 29340505
TI - [Anthropology of Health in the Americas: Contextualizations and suggestions].
PMID- 29340504
TI - Strategies to optimize MEDLINE and EMBASE search strategies for anesthesiology
systematic reviews. An experimental study.
AB - BACKGROUND: A high-quality electronic search is essential for ensuring accuracy
and comprehensiveness among the records retrieved when conducting systematic
reviews. Therefore, we aimed to identify the most efficient method for searching
in both MEDLINE (through PubMed) and EMBASE, covering search terms with variant
spellings, direct and indirect orders, and associations with MeSH and EMTREE
terms (or lack thereof). DESIGN AND SETTING: Experimental study. UNESP, Brazil.
METHODS: We selected and analyzed 37 search strategies that had specifically been
developed for the field of anesthesiology. These search strategies were adapted
in order to cover all potentially relevant search terms, with regard to variant
spellings and direct and indirect orders, in the most efficient manner. RESULTS:
When the strategies included variant spellings and direct and indirect orders,
these adapted versions of the search strategies selected retrieved the same
number of search results in MEDLINE (mean of 61.3%) and a higher number in EMBASE
(mean of 63.9%) in the sample analyzed. The numbers of results retrieved through
the searches analyzed here were not identical with and without associated use of
MeSH and EMTREE terms. However, association of these terms from both controlled
vocabularies retrieved a larger number of records than did the use of either one
of them. CONCLUSIONS: In view of these results, we recommend that the search
terms used should include both preferred and non-preferred terms (i.e. variant
spellings and direct/indirect order of the same term) and associated MeSH and
EMTREE terms, in order to develop highly-sensitive search strategies for
systematic reviews.
PMID- 29340507
TI - [Health care practices among people living with diabetes: an anthropological,
ethnographical approach with a gender perspective].
AB - Diabetes, a disease that constitutes a syndrome, is growing more quickly in
societies with precarious living and working conditions. Daily care practices are
fundamental in preventing it from progressing. This work shows the heuristic and
interpretative value and the explanatory potential of an ethnographic approach
and a gender perspective in the analysis of care practices in a group of elder
adults living with type 2 diabetes. The research was carried out with diabetes
group participants and health professionals in a primary healthcare center in
Jose Leon Suarez, municipality of San Martin, province of Buenos Aires, during
the period 2013-2016. We identified and analyzed care activities (including self
care) that resulted from the authoritative knowledge of the group in connection
with the healthcare center professionals. Such individual, group and collective
actions generate care logics that promote care of oneself. The methodological
proposal of this study is framed within the tradition of collaborative fieldwork.
PMID- 29340506
TI - [On ethnographic positions in the anthropology of health in South America].
AB - Ethnographies on health issues in populations that live in conditions of poverty,
inequality and segregation have proliferated over the last decades in South
America. The aim of this article is to problematize - preliminarily - certain
patterns in the positions and relations of ethnographers with respect to study
subjects and populations during their fieldwork and in the writing of study
results. This paper examines the relationships between these ethnographic
positions and the dominant theoretical perspectives in the region. In addition,
this article explores briefly the resolution power as well as the sensibilities,
theoretical maps, and meanings of such positions in light of power logics,
symbolic economies, and diverse manners of accumulation by dispossession in this
geographical area.
PMID- 29340508
TI - [Space, time and power in hospital health care: Contributions based on the
ethnography of an obstetric center].
AB - This paper presents the results of an ethnographic study of an obstetric center
within a hospital of Greater Buenos Aires and an analysis of the spatio-temporal
dimension of hospital care. The fieldwork, carried out between 2007 and 2011,
followed the everyday dynamics of the hospital and included observation in the
obstetrics unit (waiting areas, the obstetric center where births and emergencies
receive care, and the ambulatory care, ultrasound, and hospitalization rooms,
among others) as well as spaces such as the appointments and statistics offices,
the office of social services, the central hall, the pharmacy, and hallway
waiting areas. Interviews were carried out with department heads, obstetricians,
nurses, social workers, staff of the laboratory and the appointment and
statistics offices, volunteers and patients. In this way, the article analyzes
the medical-bureaucratic routines in the admission and hospitalization of women
in the obstetrics center; the disputes, transactions and negotiations occurring
among professionals, patients and families; the delimitation of spaces; and the
temporal sequences and hierarchies involved in the passage from the "outside" to
the "inside" of the hospital.
PMID- 29340509
TI - Uncovering a tragic flaw in revolutionary health policies: From health and
communicative inequities to communicative justice in health.
AB - This article analyzes a contradiction facing efforts by left-leaning governments
in Latin America to transform health into a fundamental social right. Policies
and practices that confront health inequities generally fail to address
health/communicative inequities, hierarchical distributions of rights to shape
what counts as legitimate knowledge of health. This ethnographic analysis focuses
on an epidemic of a mysterious disease - identified clinically as bat-transmitted
rabies - in the Delta Amacuro rainforest of Venezuela in 2007-2008, tracing how
parents who lost 1-3 children faced acute health/communicative inequities in
clinical settings, epidemiological investigations, work with healers, news
coverage, health policy, and health communication. Taking as a point of departure
rainforest residents' demands for communicative justice in health, the analysis
draws on Menendez's notion of autoatencion in exploring how health/communicative
labor is co-produced with the labor of care.
PMID- 29340510
TI - [Tradition, improvisation and modernity in Yucatecan Mayan shamanism: The suhuy
art of Juan Cob, h-men of Yaxcaba].
AB - Through the history of a Yucatecan Mayan shaman (h-men), this article analyzes
the changes and continuities in Yucatecan shamanism and, more specifically, in
one of its main functions: tsak, healing. The results presented here are part of
fieldwork carried out over 40 years, from 1976 to 2016. The author lives in a
community in central Yucatan (Tabi, Sotuta) and has carried out a number of
research studies on Yucatecan shamanism in communities in the Mexican states of
Yucatan, Campeche and Quintana Roo. Juan Cob, h-men of Yaxcaba, is not only an
informant but also the author's friend and neighbor, with whom he has created a
number of films.
PMID- 29340511
TI - [A critical examination of public policies related to indigenous health,
traditional medicine, and interculturality in Mexico (1990-2016)].
AB - Over the last 26 years, the Mexican government has developed a number of
activities and discourses around what has been called "intercultural health,"
directed especially at indigenous peoples in Mexico (some 62, according to
linguistic criteria). In this way, the government has built health care
institutions (rural centers, clinics, and hospitals) in states like Puebla,
Nayarit, Oaxaca, Chiapas, Queretaro, and Jalisco, proposing the implementation of
cultural pertinence indicators (which are minimal and inadequate). Nevertheless,
the health conditions among indigenous populations and the quality of health care
provided by public institutions continue to be precarious in terms of human and
material resources (health personnel, drugs, etc.) and discriminatory with
respect to the form and content of the provided services. This paper describes
some of the governmental interventions that purport to be institutional
improvements in the field of interculturality, but that actually represent the
continuity of arbitrary and exclusive policies.
PMID- 29340512
TI - Articulation between health services and "indigenous medicine": Anthropological
reflections on policies and reality in Brazil.
AB - This paper contributes to the dialogue between the social sciences and social
medicine in Latin America by exploring therapeutic pluralism in indigenous health
policies and services in Brazil. It reviews recent anthropological research,
concepts and current debates to critically examine Brazilian indigenous health
policy and its concept of "differentiated care," which proposes articulation
between official health practices and indigenous therapies. A number of
contradictions and tensions are present in the structural organizational of the
indigenous health subsystem at the national level and in the daily practices of
health teams at the local level. Guided by the hegemonic ideology of biomedicine,
health professionals fail to recognize the dynamics and agency expressed in
indigenous health practices.
PMID- 29340513
TI - [Family networks and the role of men in maternal health care among Mexican
indigenous women].
AB - This article reflects on maternal mortality among indigenous women in Mexico and
the changes that have occurred in care practices during pregnancy and childbirth.
Through ethnographic qualitative research in the state of Guerrero between 2008
and 2012, which included over a year of fieldwork as well as in-depth interviews
and surveys with indigenous women, the article analyzes the increasing
medicalization of reproduction, the role of family networks in gestation,
delivery and postpartum care, and the participation of men during childbirth, in
dialogue with other anthropological research on maternal health in Mexico.
Medical anthropology allows us to understand the medicalization of reproduction
in indigenous contexts and identify the tension that characterizes family care
networks, which both operate as protectors and mobilizers in seeking care and
reproduce power relations marked by gender and generational conditions.
PMID- 29340514
TI - Racial i(nter)dentification: The racialization of maternal health through the
Oportunidades program and in government clinics in Mexico.
AB - Using an ethnographic approach, this article examines the role of racialization
in health-disease-care processes specifically within the realm of maternal
health. It considers the experiences of health care administrators and providers,
indigenous midwives and mothers, and recipients of conditional cash transfers
through the Oportunidades program in Mexico. By detailing the delivery of
trainings of the Mexican Social Security Institute (IMSS) [Instituto Mexicano del
Seguro Social] for indigenous midwives and Oportunidades workshops to indigenous
stipend recipients, the article critiques the deployment of "interculturality" in
ways that inadvertently re-inscribe inequality. The concept of racial
i(nter)dentification is offered as a way of understanding processes of
racialization that reinforce discrimination without explicitly referencing race.
Racial i(nter)dentification is a tool for analyzing the multiple variables
contributing to the immediate mental calculus that occurs during quotidian
encounters of difference, which in turn structures how individuals interact
during medical encounters. The article demonstrates how unequal sociohistorical
and political conditions and differential access to economic resources become
determinants of health.
PMID- 29340515
TI - [Illegitimate patients: Undocumented immigrants' access to health care in Chile].
AB - In recent decades, Chile has become a destination for immigrants from other South
American countries, which has significantly impacted public services -
particularly the public health system - at the economic, social, and cultural
levels. The aim of this paper is to provide substantiated information on issues
concerning undocumented immigrants' access to health care in Chile. A qualitative
methodology, fundamentally an ethnography of the clinical setting, was used.
Results were then analyzed in relation to theories of power asymmetries and
interethnic relations. The research results highlight the lack of compliance with
existing regulations and the exercise of discretionary personal judgment as
barriers to access. It is concluded that in Chile immigrants in general, and
undocumented immigrants in particular, are considered to be illegitimate
patients.
PMID- 29340516
TI - [Screening program for cervical cancer: public policies and experiences of actors
who implement the program in the state of Veracruz, Mexico].
AB - The aim of this article is to analyze the way in which the Screening Program for
Cervical Cancer is carried out in a dysplasia clinic and related health centers
in the state of Veracruz, through the representations and practices of the social
actors who implement the program. In order to do so, in-depth interviews and
observations of the practices of health service providers were carried out during
different periods over the course of three years, from 2009 to 2011. Through the
information obtained, the article explores the difficulties, achievements and
results of this program as part of a public policy. Although a priority of public
health policy is to see the whole population benefit from preventive and curative
health care services, evidence shows that marginalized populations are not
benefitted by such programs; such information does not however seem to permeate
popular and medical knowledge.
PMID- 29340517
TI - [Indigenous peoples, HIV and public policy in Latin America: an exploration of
the current situations of epidemiological prevalence, prevention, care and timely
treatment].
AB - This article aims to describe and analyze the situations of epidemiological
prevalence, prevention, care and treatment of HIV in indigenous populations of
Latin America. In order to do so, 304 published materials - including
declarations, public policy and health program protocols, case studies and
literature reviews with local, national and regional scopes - were identified,
classified and analyzed. The differential social vulnerability to HIV infection
and the inequity in health care access among indigenous populations can be
attributed to the juxtaposition of factors such as structural violence, gender,
racism, and discrimination due health condition (living with HIV) as well as the
subordinated position of indigenous peoples in societies stratified not only
socially and economically but also ethnically and culturally. The few studies
done in the region on epidemiological prevalence, morbidity and mortality that
are disaggregated by ethnicity reveal alarming data highlighting the need for
further information on the epidemic in this population so as to address its
repercussions in terms of prevention, care and timely follow-up.
PMID- 29340518
TI - Rankl expression predicts poor prognosis in gastric cancer patients: results from
a retrospective and single-center analysis.
AB - The receptor activator of nuclear factor kappaB ligand (RANKL)/RANK pathway plays
an important role in the prognosis of several solid tumor types, but its role in
gastric cancer prognosis has been poorly characterized. A total of 116 gastric
cancer patients who underwent surgical resection were enrolled in this study.
Expressions of RANKL and RANK in gastric cancer tissues were detected using
immunohistochemical staining. Thirty-eight patients (33%) showed a high level of
RANKL expression and 61 patients (53%) showed a high level of RANK expression.
There was a positive correlation between expressions of RANKL and RANK (P=0.014,
r=0.221). A high level of RANKL expression indicated shorter overall survival
(OS) (P=0.008), and was associated with a higher pathological tumor/lymph
node/metastasis (pTNM) stage (P=0.035), while no significant correlation was
detected between RANK expression and clinicopathological parameters. RANKL also
predicted poor prognosis in patients with high RANK expression (P=0.008) and
Bormann's type III/IV (P=0.002). Furthermore, RANKL expression correlated with
pTNM stage according to high RANK expression (P=0.009), while no significance was
found in patients with low RANK expression (P=1.000). Together, our results
revealed that high expression of RANKL could predict worse outcomes in gastric
cancer especially combined with RANK detection, and thereby this pathway could be
a useful prognostic indicator of gastric cancer.
PMID- 29340519
TI - Evaluating the current state of the art of Huntington disease research: a
scientometric analysis.
AB - Huntington disease (HD) is an incurable neurodegenerative disorder caused by a
dominant mutation on the 4th chromosome. We aim to present a scientometric
analysis of the extant scientific undertakings devoted to better understanding
HD. Therefore, a quantitative study was performed to examine the current state-of
the-art approaches that foster researchers' understandings of the current
knowledge, research trends, and research gaps regarding this disorder. We
performed literature searches of articles that were published up to September
2016 in the "ISI Web of ScienceTM" (http://apps.webofknowledge.com/). The keyword
used was "Huntington disease". Of the initial 14,036 articles that were obtained,
7732 were eligible for inclusion in the study according to their relevance. Data
were classified according to language, country of publication, year, and area of
concentration. The country leader regarding the number of studies published on HD
is the United States, accounting for nearly 30% of all publications, followed by
England and Germany, who have published 10 and 7% of all publications,
respectively. Regarding the language in which the articles were written, 98% of
publications were in English. The first publication to be found on HD was
published in 1974. A surge of publications on HD can be seen from 1996 onward. In
relation to the various knowledge areas that emerged, most publications were in
the fields of neuroscience and neurology, likely because HD is a
neurodegenerative disorder. Publications written in areas such as psychiatry,
genetics, and molecular biology also predominated.
PMID- 29340520
TI - Analysis of serum microRNA expression in male workers with occupational noise
induced hearing loss.
AB - Occupational noise-induced hearing loss (ONIHL) is a prevalent occupational
disorder that impairs auditory function in workers exposed to prolonged noise.
However, serum microRNA expression in ONIHL subjects has not yet been studied. We
aimed to compare the serum microRNA expression profiles in male workers of ONIHL
subjects and controls. MicroRNA microarray analysis revealed that four serum
microRNAs were differentially expressed between controls (n=3) and ONIHL subjects
(n=3). Among these microRNAs, three were upregulated (hsa-miR-3162-5p, hsa-miR
4484, hsa-miR-1229-5p) and one was downregulated (hsa-miR-4652-3p) in the ONIHL
group (fold change >1.5 and Pbon value <0.05). Real time quantitative PCR was
conducted for validation of the microRNA expression. Significantly increased
serum levels of miR-1229-5p were found in ONIHL subjects compared to controls
(n=10 for each group; P<0.05). A total of 659 (27.0%) genes were predicted as the
target genes of miR-1229-5p. These genes were involved in various pathways, such
as mitogen-activated protein kinase (MAPK) signaling pathway. Overexpression of
miR-1229-5p dramatically inhibited the luciferase activity of 3' UTR segment of
MAPK1 (P<0.01). Compared to the negative control, HEK293T cells expressing miR
1229-5p mimics showed a significant decline in mRNA levels of MAPK1 (P<0.05).
This preliminary study indicated that serum miR-1229-5p was significantly
elevated in ONIHL subjects. Increased miR-1229-5p may participate in the
pathogenesis of ONIHL through repressing MAPK1 signaling.
PMID- 29340521
TI - Organic solvent exposure and contrast sensitivity: comparing men and women.
AB - The goal of this study was to compare the visual contrast sensitivity (CS) of men
and women exposed and not exposed to organic solvents. Forty-six volunteers of
both genders aged between 18 and 41 years (mean+/-SD=27.72+/-6.28) participated.
Gas station attendants were exposed to gas containing 46.30 ppm of solvents at a
temperature of 304+/-274.39 K, humidity of 62.25+/-7.59% and ventilation of
0.69+/-0.46 m/s (a passive gas chromatography-based sampling method was used
considering the microclimate variables). Visual CS was measured via the
psychophysical method of two-alternative forced choice using vertical sinusoidal
gratings with spatial frequencies of 0.2, 0.5, 1.0, 2.0, 5.0, 10.0, and 16.0 cpd
(cycles per degree) and an average luminance of 34.4 cd/m2. The results showed
that visual CS was significantly lower (P<0.05) in the following groups: i)
exposed men compared to unexposed men at frequencies of 0.2, 0.5, 1.0, and 2.0
cpd; ii) exposed women compared to unexposed women at a frequency of 5.0 cpd; and
iii) exposed women compared to exposed men at a frequency of 0.5 cpd, even at
exposures below the tolerance limit (300 ppm). These results suggest that the
visual CS of exposed men was impaired over a wider range of spatial frequencies
than that of exposed women. This difference may have been due to the higher body
fat content of women compared to that of men, suggesting that body fat in women
can serve as a protective factor against neurotoxic effects.
PMID- 29340522
TI - Penile microvascular endothelial function in hypertensive patients: effects of
acute type 5 phosphodiesterase inhibition.
AB - The primary aim of this study was to evaluate penile endothelial microvascular
function in patients with primary arterial hypertension and age-matched
normotensive subjects using laser speckle contrast imaging (LSCI). Additionally,
we analyzed the acute penile microvascular effects induced by oral
phosphodiesterase type 5 inhibitor (sildenafil; SIL) administration. Endothelium
dependent microvascular reactivity was evaluated in the penises and forearms of
hypertensive patients (aged 58.8+/-6.6 years, n=34) and age-matched healthy
volunteers (n=33) at rest and 60 min following oral SIL (100 mg) administration.
LSCI was coupled with cutaneous acetylcholine (ACh) iontophoresis using
increasing anodal currents. Basal penile cutaneous vascular conductance (CVC)
values were not significantly different between control subjects and hypertensive
individuals. Penile CVC values increased significantly after SIL administration
in control (P<0.0001) and hypertensive (P<0.0001) subjects. Peak CVC values were
not different between the two groups during penile ACh iontophoresis before SIL
administration (P=0.2052). Peak CVC values were higher in control subjects than
in hypertensive subjects after SIL administration (P=0.0427). Penile endothelium
dependent microvascular function is, to some extent, preserved in patients
presenting with primary arterial hypertension under effective anti-hypertensive
treatment. LSCI may be a valuable non-invasive tool for the evaluation of penile
vascular responses to phosphodiesterase type 5 inhibitor.
PMID- 29340523
TI - A case of severe glutathione synthetase deficiency with novel GSS mutations.
AB - Glutathione synthetase deficiency (GSSD) is a rare inborn error of glutathione
metabolism with autosomal recessive inheritance. The severe form of the disease
is characterized by acute metabolic acidosis, usually present in the neonatal
period with hemolytic anemia and progressive encephalopathy. A case of a male
newborn infant who had severe metabolic acidosis with high anion gap, hemolytic
anemia, and hyperbilirubinemia is reported. A high level of 5-oxoproline was
detected in his urine and a diagnosis of generalized GSSD was made. DNA sequence
analysis revealed the infant to be compound heterozygous with two mutations,
c.738dupG in exon 8 of GSS gene resulting in p.S247fs and a repetitive sequence
in exon 3 of GSS gene. Treatment after diagnosis of GSSD included supplementation
with antioxidants and oral sodium hydrogen bicarbonate. However, he maintained a
variable degree of metabolic acidosis and succumbed shortly after his parents
requested discontinuation of therapy because of dismal prognosis and medical
futility when he was 18 days old.
PMID- 29340524
TI - Efficacy of removal of cariogenic bacteria and carious dentin by ablation using
different modes of Er:YAG lasers.
AB - The primary objective of this in vitro study was to evaluate the efficiency of
removal of cariogenic bacteria and carious dentin by ablation using two lasers:
fluorescence-feedback controlled (FFC) Er:YAG laser and different pulses of
Er:YAG laser based on variable square pulse technology (VSPt). The secondary
objective was to measure the temperature during laser ablation of carious tissue.
Seventy-two extracted human molars were used in this study. Sixty teeth with
carious dentin were randomly divided into four experimental groups according to
the treatment for caries removal: group 1: 400 us (FFC group); group 2: super
short pulse (SSP group, 50 us pulse); group 3: medium short pulse (MSP group, 100
us pulse); group 4: short pulse (SP group, 300 us pulse) and one positive control
group with no treatment. Twelve teeth without carious lesion were used as a
negative control group. After caries removal, swabs were taken with cotton
pellets and real-time PCR analysis was performed. During caries ablation, a
thermal infrared camera was used to measure the temperature changes. In all
experimental groups, specimens were free of bacterial contamination after the
treatment. In the SSP, MSP and SP groups, temperatures measured during caries
ablation were significantly higher compared to temperatures in the FFC group
(P<0.001). In this in vitro study, laser treatment for removal of carious dentin
and cariogenic bacteria was an efficient treatment modality without causing
excessive temperatures that might adversely affect pulp vitality.
PMID- 29340525
TI - Time collection and storage conditions of lipid profile.
AB - The stability of samples is crucial for getting reliable concentrations of many
analytes, including lipid profile. Thus, the goal of this study was to analyze
lipid profile under different storage and temperature conditions. This was a
prospective study with 809 patients of both genders. Total cholesterol,
triglycerides, high-density lipoprotein cholesterol, low density lipoprotein
cholesterol and non-high-density lipoprotein were measured within 1 h from
collection at room temperature, after 2-3 h of refrigeration (8 degrees C) and
after 4-5 h at room temperature. The processing time and storage conditions did
not affect the analytes measured. These findings are important for multicenter
studies, because of the difficulties related to centrifugation and freezing of
samples immediately after collection.
PMID- 29340526
TI - Simulating the behavior of patients who leave a public hospital emergency
department without being seen by a physician: a cellular automaton and agent
based framework.
AB - The objective of this study was to develop an agent based modeling (ABM)
framework to simulate the behavior of patients who leave a public hospital
emergency department (ED) without being seen (LWBS). In doing so, the study
complements computer modeling and cellular automata (CA) techniques to simulate
the behavior of patients in an ED. After verifying and validating the model by
comparing it with data from a real case study, the significance of four
preventive policies including increasing number of triage nurses, fast-track
treatment, increasing the waiting room capacity and reducing treatment time were
investigated by utilizing ordinary least squares regression. After applying the
preventing policies in ED, an average of 42.14% reduction in the number of
patients who leave without being seen and 6.05% reduction in the average length
of stay (LOS) of patients was reported. This study is the first to apply CA in an
ED simulation. Comparing the average LOS before and after applying CA with actual
times from emergency department information system showed an 11% improvement. The
simulation results indicated that the most effective approach to reduce the rate
of LWBS is applying fast-track treatment. The ABM approach represents a flexible
tool that can be constructed to reflect any given environment. It is also a
support system for decision-makers to assess the relative impact of control
strategies.
PMID- 29340527
TI - Cardiac protein expression patterns are associated with distinct inborn exercise
capacity in non-selectively bred rats.
AB - In the present study, we successfully demonstrated for the first time the
existence of cardiac proteomic differences between non-selectively bred rats with
distinct intrinsic exercise capacities. A proteomic approach based on two
dimensional gel electrophoresis coupled to mass spectrometry was used to study
the left ventricle (LV) tissue proteome of rats with distinct intrinsic exercise
capacity. Low running performance (LRP) and high running performance (HRP) rats
were categorized by a treadmill exercise test, according to distance run to
exhaustion. The running capacity of HRPs was 3.5-fold greater than LRPs. Protein
profiling revealed 29 differences between HRP and LRP rats (15 proteins were
identified). We detected alterations in components involved in metabolism,
antioxidant and stress response, microfibrillar and cytoskeletal proteins.
Contractile proteins were upregulated in the LVs of HRP rats (alpha-myosin heavy
chain-6, myosin light chain-1 and creatine kinase), whereas the LVs of LRP rats
exhibited upregulation in proteins associated with stress response (aldehyde
dehydrogenase 2, alpha-crystallin B chain and HSPbeta-2). In addition, the
cytoskeletal proteins desmin and alpha-actin were upregulated in LRPs. Taken
together, our results suggest that the increased contractile protein levels in
HRP rats partly accounted for their improved exercise capacity, and that proteins
considered risk factors to the development of cardiovascular disease were
expressed in higher amounts in LRP animals.
PMID- 29340528
TI - Synthesis and anti-myocarditis activity in a multifunctional lanthanide
microporous metal-organic framework with 1D helical chain building units.
AB - A new microporous lanthanide metal-organic framework, {[Yb(BTB)(H2O) (DEF)2}n (1,
DEF=N,N-Diethylformamide), with 1D nano-sized channels has been constructed by
bridging helical chain secondary building units with 1,3,5-benzenetrisbenzoic
acid (H3BTB) ligand. Structural characterization suggests that this complex
crystallizes in the hexagonal space group P6122 and possesses 1D triangular
channels with coordinated water molecules pointing to the channel center. In
addition, anti-myocarditis properties of compound 1 were evaluated in vivo. The
results showed that compound 1 can improve hemodynamic parameters of, and it may
be a good therapeutic option for heart failure in the future.
PMID- 29340529
TI - Association between syndecan-1 and renal function in adolescents with excess
weight: evidence of subclinical kidney disease and endothelial dysfunction.
AB - Excess weight (overweight and obesity) is associated with kidney and
cardiovascular disease. The aim of this study was to investigate the association
between syndecan-1 and renal function among adolescents with excess weight. A
total of 56 students from a public school at Fortaleza, CE, Brazil, were
investigated. The adolescents were submitted to anthropometric evaluation,
including weight, height, blood pressure and body mass index. Blood and urine
samples were collected for the determination of serum lipids (total cholesterol,
high density lipoprotein cholesterol, low density lipoprotein cholesterol,
triglycerides), and the endothelial injury biomarker syndecan-1. Participants'
mean age was 16+/-1 years (range 14-19 years), and 68% were females. Overweight
was observed in 4 cases (7.1%) and obesity in 7 (12.5%). Changes in serum lipid
levels were more frequent in the overweight group. A positive correlation between
syndecan-1 and serum creatinine (r=0.5, P=0.001) and triglycerides (r=0.37,
P=0.004), and a negative correlation with glomerular filtration rate (r=-0.33,
P=0.02) were found. These findings suggest that adolescents with excess weight
present incipient changes at the cellular level that make them more vulnerable to
the development of kidney and cardiovascular diseases.
PMID- 29340530
TI - The use of biosimilar medicines in oncology - position statement of the Brazilian
Society of Clinical Oncology (SBOC).
AB - A biosimilar is a biologic product that is similar to a reference
biopharmaceutical product, the manufacturing process of which hinders the ability
to identically replicate the structure of the original product, and therefore, it
cannot be described as an absolute equivalent of the original medication. The
currently available technology does not allow for an accurate copy of complex
molecules, but it does allow the replication of similar molecules with the same
activity. As biosimilars are about to be introduced in oncology practice, these
must be evaluated through evidence-based medicine. This manuscript is a position
paper, where the Brazilian Society of Clinical Oncology (SBOC) aims to describe
pertinent issues regarding the approval and use of biosimilars in oncology. As a
working group on behalf of SBOC, we discuss aspects related to definition,
labeling/nomenclature, extrapolation, interchangeability, switching, automatic
substitution, clinical standards on safety and efficacy, and the potential impact
on financial burden in healthcare. We take a stand in favor of the introduction
of biosimilars, as they offer a viable, safe, and cost-effective alternative to
the biopharmaceutical products currently used in cancer. We hope this document
can provide valuable information to support therapeutic decisions that maximize
the clinical benefit for the thousands of cancer patients in Brazil and can
contribute to expedite the introduction of this new drug class in clinical
practice. We expect the conveyed information to serve as a basis for further
discussion in Latin America, this being the first position paper issued by a
Latin American Oncology Society.
PMID- 29340531
TI - Prenatal development of the sound transmitting apparatus in different embryonic
stages of Malpolon monsspesulanus (squamata-serpentes).
AB - The developmental investigation of sound transmitting apparatus is important in
understanding the ontogenetic processes behind morphological diversity. The
development of sound conducting apparatus was studied in Montpellier snake;
Malpolon monspessulanus at 6.5, 7.2, 8.3 and 9.3 cm total body lengths using
light microscopy study. The columella auris firstly appeared as undifferentiated
rod shape mesenchymal cells. As the growth proceeded, it chondrified and
differentiates into two main parts. In addition, the viscerocranium components
which participate in formation of sound transmitting apparatus undergo critical
organization. In more advanced stages, procartilagenous stylohyal chondrified and
fuse with the well organized quadrate. These data considered as a base for
functional and molecular mechanisms of sound transmitting apparatus studies and
identification of diseases that may infect them.
PMID- 29340532
TI - Effects of light-dark cycle on the spatial distribution and feeding activity of
fish larvae of two co-occurring species (Pisces: Hypophthalmidae and Sciaenidae)
in a Neotropical floodplain lake.
AB - Most studies on mechanisms regulating fish larvae processes have focused on
assessing the isolated effects of food distribution and feeding behavior.
However, in natural ecosystems, fish larvae may strongly interact with
zooplankton organisms in an array of complex, direct and indirect
interdependencies. This study analyzed the spatial distribution, diet and feeding
behavior of early stages of Hypophthalmus edentatus and Plagioscion
squamosissimus, two fish species co-occurring in an isolated floodplain lake,
during the light-dark cycle. Larvae fed more actively during dark periods (dusk
and night) when they migrated toward the surface of the lake, and remained on the
bottom and fed less during light periods (day and dawn). Cladocerans represented
the most frequent prey in the diet of H. edentatus larvae. In turn, P.
squamosissimus larvae initially preferred cladocerans and, as they developed,
included calanoid copepods in the diet. Significant differences were detected in
the frequencies of food items consumed during larval development, which could be
related to a better ability of the most developed stages to explore the
environment in search of other prey.
PMID- 29340533
TI - More than two decades after the introduction of Limnoperna fortunei (Dunker 1857)
in La Plata Basin.
AB - The golden mussel, Limnoperna fortunei, is an Asian freshwater bivalve introduced
in South America in the beginning of the 1990's, probably through ballast water
releases in La Plata River estuary. It dispersed north through Parana, Uruguay
and Paraguay Rivers. The study evaluated the macroscale (18 degrees to 34
degrees S; 45 degrees to 60 degrees W) distribution of L. fortunei (larval
stages) in the main rivers and reservoirs of La Plata Basin. Samplings were
performed through 68 um vertical plankton net hauls. Limnological variables were
simultaneously determined. Larvae abundance correlated significantly with oxygen
(positively) in summer, with temperature (positively) in winter and with total
phosphorus and total nitrogen (both negatively) in winter. We expected densities
to decrease towards north (latitudinal gradient) and increase in lentic
conditions (reservoirs). Despite maximum density was found near the introduction
point (La Plata River) similar value was also observed 2,000 km north (Paraguay
River). The first hypothesis was refuted. The second hypothesis was partially
accepted. Abundances were consistently higher in summer. Higher trophic
conditions and fast flow seem to inhibit population growth. Food resources
(chlorophyll a) locally influenced temporal variation. Limnoperna fortunei is
widely distributed in La Plata basin, reaching high larval densities superior to
10,000 ind. m-3, in all major sub-basins. The species exhibits a high intrinsic
dispersal ability (free planktonic larvae), wide tolerance to environmental
factors and dispersion is potentialized by natural dispersion processes (e.g.
fauna displacement) and human facilitation (e.g. commercial navigation).
PMID- 29340534
TI - What every intensivist should know about intensive care unit admission criteria.
PMID- 29340535
TI - Prevalence of cytomegalovirus disease in kidney transplant patients in an
intensive care unit.
AB - OBJECTIVES: To define the frequency of cytomegalovirus disease among kidney
transplant patients in an intensive care unit in which this complication was
suspected and to identify predisposing factors and their possible impact on
clinical outcome. METHODS: Retrospective observational study in which kidney
transplant patients over the age of 18 years were hospitalized for any reason in
an intensive care unit with at least one collection of samples to test for the
presence of antigenemia or cytomegalovirus via polymerase chain reaction during
hospitalization. Cytomegalovirus disease was defined as positive antigenemia or
polymerase chain reaction above 500 copies/mL in the presence of symptoms and in
the appropriate clinical setting, as judged by the attending physician. RESULTS:
A total of 99 patients were included (age: 53.4 +/- 12.8 years, 71.6% male).
Cytomegalovirus disease was diagnosed in 39 patients (39.4%). Respiratory
symptoms (51%), non-specific clinical worsening (20%) or gastrointestinal
symptoms (14%) were the main reasons for exam collection. Transplant time was
lower in those with cytomegalovirus disease than in those without this diagnosis
(6.5 months and 31.2 months, p = 0.001), along with pulse therapy in the last 6
months (41% and 16.9%, p = 0.008) and previous use of thymoglobulin in the last
year (35.9% and 6.8%, p < 0.001). In the logistic regression model, only the
transplant time and the use of thymoglobulin were associated with a higher
frequency of cytomegalovirus. There was no difference in clinical evolution
between patients with and without cytomegalovirus disease. CONCLUSION: In kidney
transplant patients suspected of cytomegalovirus disease, the prevalence was
high. Transplant time less than 6 months, and the use of thymoglobulin in the
last year should increase the intensivist's suspicion for this complication.
PMID- 29340536
TI - Assessment of PIM-2 performance among surgical patients with heart disease and
correlation of results with RACHS-1.
AB - OBJECTIVE: To assess the performance of the Pediatric Index of Mortality (PIM) 2
and the Risk Adjustment for Congenital Heart Surgery (RACHS) in the postoperative
period of congenital heart disease patients. METHODS: Retrospective cross
sectional study. Data were collected from patient records to generate the scores
and predictions using recommended techniques, demographic data and outcomes. The
Mann-Whitney test, Hosmer-Lemeshow test, standardized mortality rate, area under
the receiver operating characteristic (ROC) curve, chi square test, Poisson
regression with robust variance and Spearman's test were used for statistical
analysis. RESULTS: A total of 263 patients were evaluated, and 72 died (27.4%).
These patients presented significantly higher PIM-2 values than survivors (p <
0.001). In the RACHS-1 classification, mortality was progressively higher
according to the complexity of the procedure, with a 3.24-fold increase in the
comparison between groups 6 and 2. The area under the ROC curve for PIM-2 was
0.81 (95%CI 0.75 - 0.87), while for RACHS-1, it was 0.70 (95%CI 0.63 - 0.77). The
RACHS presented better calibration power in the sample analyzed. A significantly
positive correlation was found between the results of both scores (rs = 0.532; p
< 0.001). CONCLUSION: RACHS presented good calibration power, and RACHS-1 and PIM
2 demonstrated good performance with regard to their discriminating capacities
between survivors and non-survivors. Moreover, a positive correlation was found
between the results of the two risk scores.
PMID- 29340537
TI - Bedside ultrasound is a practical measurement tool for assessing muscle mass.
AB - OBJECTIVE: To evaluate the intra- and inter-reliability and the ease of measuring
the quadriceps muscle thickness using bedside ultrasound. METHODS: This is a
prospective, observational study. The assessment of quadriceps muscle thickness
was performed at two reference points and was quantified using portable B-mode
ultrasound in two healthy volunteers. For standardization of measurements and
validation of image collections, the team was trained through theoretical and
practical classes, with a 6-hour workload. RESULTS: A total of 112 images were
examined by the coach and compared with the trainees. Pearson's correlation
analysis found an excellent relationship between the coach and all trainees (R2 >
0.90). The best association was between the coach and the dietitians (R2: 0.99; p
< 0.001), and the worst association was between the coach and the medical
trainees (R2: 0.92; p < 0.001). In the Bland-Altman comparison, the highest error
rate found between coach and trainees was 5.12% (95% confidence interval [CI]
3.64-12.37), and the lowest was 1.01% (95%CI 0.72 - 2.58); the highest bias of
the values described was -0.12 +/- 0.19, and the lowest was -0.01 +/- 0.04.
CONCLUSION: The data analyzed showed a good correlation between the measurements
made by the coach and trainees, indicating that ultrasound of the quadriceps
muscle is a viable and easily applicable tool.
PMID- 29340538
TI - Autonomic nervous system monitoring in intensive care as a prognostic tool.
Systematic review.
AB - OBJECTIVE: To present a systematic review of the use of autonomic nervous system
monitoring as a prognostic tool in intensive care units by assessing heart rate
variability. METHODS: Literature review of studies published until July 2016
listed in PubMed/Medline and conducted in intensive care units, on autonomic
nervous system monitoring, via analysis of heart rate variability as a prognostic
tool (mortality study). The following English terms were entered in the search
field: ("autonomic nervous system" OR "heart rate variability") AND ("intensive
care" OR "critical care" OR "emergency care" OR "ICU") AND ("prognosis" OR
"prognoses" OR "mortality"). RESULTS: There was an increased likelihood of death
in patients who had a decrease in heart rate variability as analyzed via heart
rate variance, cardiac uncoupling, heart rate volatility, integer heart rate
variability, standard deviation of NN intervals, root mean square of successive
differences, total power, low frequency, very low frequency, low frequency/high
frequency ratio, ratio of short-term to long-term fractal exponents, Shannon
entropy, multiscale entropy and approximate entropy. CONCLUSION: In patients
admitted to intensive care units, regardless of the pathology, heart rate
variability varies inversely with clinical severity and prognosis.
PMID- 29340539
TI - The spectrum of cardiovascular effects of dobutamine - from healthy subjects to
septic shock patients.
AB - Dobutamine is the inotrope most commonly used in septic shock patients to
increase cardiac output and correct hypoperfusion. Although some experimental and
clinical studies have shown that dobutamine can improve systemic and regional
hemodynamics, other research has found that its effects are heterogenous and
unpredictable. In this review, we analyze the pharmacodynamic properties of
dobutamine and its physiologic effects. Our goal is to show that the effects of
dobutamine might differ between healthy subjects, in experimental and clinical
cardiac failure, in animal models and in patients with septic shock. We discuss
evidence supporting the claim that dobutamine, in septic shock, frequently
behaves as a chronotropic and vasodilatory drug, without evidence of inotropic
action. Since the side effects are very common, and the therapeutic benefits are
unclear, we suggest that dobutamine should be used cautiously in septic shock.
Before a definitive therapeutic decision, the efficacy and tolerance of
dobutamine should be assessed during a brief time with close monitoring of its
positive and negative side effects.
PMID- 29340540
TI - Toxic epidermal necrolysis: a paradigm of critical illness.
AB - Toxic epidermal necrolysis is an adverse immunological skin reaction secondary in
most cases to the administration of a drug. Toxic epidermal necrolysis, Stevens
Johnson syndrome, and multiform exudative erythema are part of the same disease
spectrum. The mortality rate from toxic epidermal necrolysis is approximately
30%. The pathophysiology of toxic epidermal necrolysis is similar in many
respects to that of superficial skin burns. Mucosal involvement of the ocular and
genital epithelium is associated with serious sequelae if the condition is not
treated early. It is generally accepted that patients with toxic epidermal
necrolysis are better treated in burn units, which are experienced in the
management of patients with extensive skin loss. Treatment includes support,
elimination, and coverage with biosynthetic derivatives of the skin in affected
areas, treatment of mucosal involvement, and specific immunosuppressive
treatment. Of the treatments tested, only immunoglobulin G and cyclosporin A are
currently used in most centers, even though there is no solid evidence to
recommend any specific treatment. The particular aspects of the treatment of this
disease include the prevention of sequelae related to the formation of synechiae,
eye care to prevent serious sequelae that can lead to blindness, and specific
immunosuppressive treatment. Better knowledge of the management principles of
toxic epidermal necrolysis will lead to better disease management, higher
survival rates, and lower prevalence of sequelae.
PMID- 29340542
TI - Sepsis definitions.
PMID- 29340541
TI - Safety criteria to start early mobilization in intensive care units. Systematic
review.
AB - Mobilization of critically ill patients admitted to intensive care units should
be performed based on safety criteria. The aim of the present review was to
establish which safety criteria are most often used to start early mobilization
for patients under mechanical ventilation admitted to intensive care units.
Articles were searched in the PubMed, PEDro, LILACS, Cochrane and CINAHL
databases; randomized and quasi-randomized clinical trials, cohort studies,
comparative studies with or without simultaneous controls, case series with 10 or
more consecutive cases and descriptive studies were included. The same was
performed regarding prospective, retrospective or cross-sectional studies where
safety criteria to start early mobilization should be described in the Methods
section. Two reviewers independently selected potentially eligible studies
according to the established inclusion criteria, extracted data and assessed the
studies' methodological quality. Narrative description was employed in data
analysis to summarize the characteristics and results of the included studies;
safety criteria were categorized as follows: cardiovascular, respiratory,
neurological, orthopedic and other. A total of 37 articles were considered
eligible. Cardiovascular safety criteria exhibited the largest number of
variables. However, respiratory safety criteria exhibited higher concordance
among studies. There was greater divergence among the authors regarding
neurological criteria. There is a need to reinforce the recognition of the safety
criteria used to start early mobilization for critically ill patients; the
parameters and variables found might contribute to inclusion into service
routines so as to start, make progress and guide clinical practice.
PMID- 29340543
TI - COLOSTOMY CLOSURE: RISK FACTORS FOR COMPLICATIONS.
AB - BACKGROUND: : The restoration of intestinal continuity is an elective procedure
that is not free of complications; on the contrary, many studies have proven a
high level of morbidity and mortality. It is multifactorial, and has factors
inherent to the patients and to the surgical technique. AIM: : To identify
epidemiological features of patients that underwent ostomy closure analyzing the
information about the surgical procedure and its arising complications. METHOD: :
It was realized a retrospective analysis of medical records of patients who
underwent ostomy closure over a period of seven years (2009-2015). RESULTS: : A
total of 39 patients were included, 53.8% male and 46.2% female, with mean age of
52.4 years. Hartmann's procedure and ileostomy were the mainly reasons for
restoration of intestinal continuity, representing together 87%. Termino-terminal
anastomosis was performed in 71.8% of cases, by using mainly the manual
technique. 25.6% developed complications, highlighting anastomotic leakage; there
were three deaths (7.6%). The surgical time, the necessity of ICU and blood
transfusion significantly related to post-operative complications. CONCLUSION: :
It was found that the majority of the patients were male, with an average age of
52 years. It was observed that the surgical time, the necessity of blood
transfusion and ICU were factors significantly associated with complications.
PMID- 29340544
TI - INTERESFINCTERIAL LIGATION OF FISTULA TRACT (LIFT) FOR PATIENTS WITH ANAL
FISTULAS: A BRAZILIAN BI-INSTITUTIONAL EXPERIENCE.
AB - BACKGROUND : The best treatment for anal fistula should extirpate infection and
promote healing of the tract, whilst preserving the anal sphincter complex and
full continence. AIM: To analyze the success rate after a modified technique for
ligation of the intersphincteric fistula tract (LIFT) for patients with anal
fistulas. METHODS: A prospective (observational cohort study) Brazilian bi
institutional experience with a modified (ligation of the intersphincteric
fistula tract without excision) LIFT technique was undertaken. A clinical
database was settled for the following variables: age, gender, BMI,
comorbidities, distance between external orifice and the anus, previous fistula
surgery, type of fistula, operative time, intra- and postoperative complications,
duration of follow-up, and success rate. RESULTS: Between November 2015 and
January 2017, 38 patients with transsphincteric fistulas were operated on using
the modified LIFT procedure. Seventeen (44.7%) were men. Median age was 41 (18
67) years. Median BMI was 26.4 (22-38) kg/m2. Five (13.2%) had undergone previous
surgery. The fistula was transsphincteric in all cases. Median follow-up was 32
(range, 14-56) weeks. Success was observed in 30 (79%) patients. CONCLUSIONS: The
LIFT technique without excision of the fistula tract proved to be safe and
effective for transsphincteric anal fistulas.
PMID- 29340545
TI - EFFECTS OF COLD ISCHEMIA TIME ON HEPATIC ALLOGRAFT FUNCTION.
AB - BACKGROUND
: Cold ischemia time is related to success
of liver transplantation.
AIM
: To compare the impact
of cold ischemia time on allografts locally collected to those collected
distantly.
METHODS
: Were evaluated 83
transplantations. The patients were divided in two groups: those who received
liver grafts collected from cities out of Curitiba (n=42) and locally (n=41).
From the donors were compared: cause of death, days at ICU, cardiac arrest,
vasoactive drugs, lab exams, gender, age, and BMI. Were compared the subsequent
information of receptors: cold ischemia time, warm ischemia time, length of
surgery, lab exams, etiology of cirrhosis, MELD score, age, gender, histology of
graft, use of vasoactive drugs, and blood components transfusion. Were evaluated
the correlation between cold ischemia time and lab results.
RESULTS
: The liver grafts collected from other
cities were submitted to a longer cold ischemia time (500+/-145 min) compared to
those locally collected (317,85+/-105 min). Donors from other cities showed a
higher serum sodium level at donation (154+/-16 mEq/dl) compared to those from
Curitiba (144+/-10 mEq/dl). The length of cold ischemia time was related to serum
levels of ALT and total bilirubin.
CONCLUSION
: Liver
grafts distantly collected underwent longer cold ischemia times, although it
caused neither histologic injuries nor higher transfusion demands. There is a
correlation between cold ischemia time and hepatic injury, translated by
elevation of serum ALT and total bilirubin levels.
PMID- 29340546
TI - PRE AND POSTOPERATIVE PH MONITORING AND WEIGHT LOSS ANALYSIS IN PATIENTS
UNDERGOING GASTRIC PLICATION IN ASSOCIATION WITH FUNDOPLICATION.
AB - BACKGROUND : Obese patients with gastroesophageal reflux disease with
pathological pH monitoring result may benefit from surgical treatment which is
based on the fundoplication technique in association with laparoscopic gastric
plication. The Nissen surgery is the gold standard for surgical treatment of
gastroesophageal reflux disease, whereas laparoscopic gastric plication is a
restrictive surgery that consists of the invagination of the greater curvature,
resulting in weight loss. AIM: To compare pre and postoperative pHmetry results
and to evaluate weight loss in patients submitted to gastroplasty with
fundoplication. METHOD: Sixteen patients with class I body mass index with
symptoms of gastroesophageal reflux with changes of stomach pH and/or erosive
esophagitis seen in endoscopy were selected The evaluation of the weight and 24-h
pH monitoring was performed preoperatively and postoperatively. The weight, body
mass index, percentage of excess weight loss and DeMeester score of patients that
underwent the surgery were evaluated pre and postoperatively. RESULTS: Regarding
pH monitoring, the average preoperative DeMeester index was 28.7, which was
followed by a significant postoperative average reduction to 2.8 (p<0,001).
Regarding the weight reduction, the average of weight loss was 13.6 kg and body
mass index of 5.3 kg/m2 (p<0.001). Furthermore, the average percentage of excess
weight loss was 53.9% (standard deviation=26.2). CONCLUSION: The combination of
Nissen surgery and gastric plication is a viable procedure and appears to be an
acceptable option for the treatment of gastroesophageal reflux disease in obese
patients, especially patients with obesity class I.
PMID- 29340547
TI - QUALITY OF LIFE AFTER VERTICAL GASTRECTOMY EVALUATED BY THE BAROS QUESTIONNAIRE.
AB - BACKGROUND
: The satisfactory outcome in the surgical
treatment of obesity must include, in addition to weight loss, a significant
change in the pre-existing comorbidities and in the quality of life of the
patients.
AIM
: To evaluate the quality of life in
the late postoperative period in patients that underwent videolaparoscopic sleeve
gastrectomy.
METHODS
: Was applied the questionnaire
"Bariatric Analysis and Reporting Outcome System" (BAROS) in patients that
underwent videolaparoscopic sleeve gastrectomy.
RESULTS
: A total of 47 patients between 21-60 years
old were evaluated. The total mean of the BMI before surgery was 43.06+/-5.87
kg/m2. The average percentage of the reduction of excess weight after surgery was
85.46+/-23.6%. The score obtained by patients in the questionnaire about the
improvement in the quality of life showed excellent (36.17%), very good (40.43%),
good (21.28%) and reasonable (2.13%) results. There was clinical improvement
after surgery in all comorbidities investigated.
CONCLUSION
: BAROS showed excellent results in
36.17%, very good in 40.43%, good in 21.28% and reasonable in 2.13%. The weight
loss was critical to improve the quality of life and offered the resolution or
clinical improvement in all of the investigated comorbidities.
PMID- 29340548
TI - THE RELATION AMONG THE PHYSICAL ACTIVITY LEVEL DURING LEISURE TIME,
ANTHROPOMETRY, BODY COMPOSITION, AND PHYSICAL FITNESS OF WOMEN UNDERWENT OF
BARIATRIC SURGERY AND AN EQUIVALENT GROUP WITH NO SURGERY.
AB - BACKGROUND: Bariatric surgery is an alternative to the obesity treatment. AIM:
To compare anthropometric variables such as body composition and physical fitness
of those who performed Roux-en-Y gastric bypass. METHODS: Were evaluated 108
women. They were subdivided in three groups: those who performed the bariatric
surgery by private health insurance (SAS, n=36); by the public health care (SUS,
n=36), and an equivalent group which did not perform the surgery (NO, n=36). Were
performed physical fitness, anthropometric and body composition tests. Was
evaluated the level of physical activity during the leisure period. RESULTS:
Statistically significant differences were observed between the groups sedentary
operated (n=28) and sedentary non-operated (n=13) on anthropometry and fat
percentage, being the highest indexes in the group operated. CONCLUSION: The
level of physical activity showed a positive influence related to anthropometric
variables, body composition of the individuals who performed the bariatric
surgery when compared to the ones non-operated.
PMID- 29340549
TI - TEACHING MODEL FOR EVALUATION OF THE ABILITY AND COMPETENCE PROGRESS IN
ENDOSUTURE IN SURGICAL SKILL LABORATORY.
AB - BACKGROUND : Laparoscopic manual suturing is probably the most difficult skill
to be acquired in minimally invasive surgery. However, laparoscopic exercise endo
sutures can be learned with a simulator and are of great practical importance and
clinical applicability, absorbing concepts that are immediately transferred to
the operating room. AIM : To assess the progression of skills competence in endo
sutures through realistic simulation model of systematized education. METHOD :
Evaluation of the progression of competence of students in three sequential
stages of training in realistic simulation, pre-test (V.1), teaching concepts
(V.2) and training station for absorption of video concepts in surgery -
ergonomics, stereotaxia, ambidexterity, haptic touch, fucral effect, applied in
the manufacture of points corresponding to a Nissen fundoplication, in endo
suture for realistic simulation. RESULTS : All students who attended the course
absorbed the video concepts in surgery; most participants showed steady and
continued improvement and during the stages of training, obtained progression of
appropriate skills, defining competence and validation of the teaching model to
achieve proficiency. CONCLUSIONS : The teaching model was adequate, safe,
revealed the profile of the student, the evolutionary powers of the endo-sutures
performance and critical analysis of the training to achieve proficiency in
bariatric procedures.
PMID- 29340550
TI - MODIFIED HEIDELBERG TECHNIQUE FOR PANCREATIC ANASTOMOSIS.
AB - BACKGROUND
: Pancreatic fistula is a major cause of
morbidity and mortality after pancreatoduodenectomy. To prevent this
complication, many technical procedures have been described.
AIM: To
present a novel technique based on slight modifications of the original
Heidelberg technique, as new pancreatojejunostomy technique for reconstruction of
pancreatic stump after pancreatoduodenectomy and present initial results.
METHOD: The technique was used for patients with soft or hard pancreas and
with duct size smaller or larger than 3 mm. The stitches are performed with 5-0
double needle prolene at the 2 o'clock, 4 o'clock, 6 o'clock, 8 o'clock, 10
o'clock, and 12 o'clock, positions, full thickness of the parenchyma. A running
suture is performed with 4-0 single needle prolene on the posterior and anterior
aspect the pancreatic parenchyma with the jejunal seromuscular layer. A plastic
stent, 20 cm long, is inserted into the pancreatic duct and extended into the
jejunal lumen. Two previously placed hemostatic sutures on the superior and
inferior edges of the remnant pancreatic stump are passed in the jejunal
seromuscular layer and tied.
RESULTS
: Seventeen
patients underwent pancreatojejunostomy after pancreatoduodenectomy for different
causes. None developed grade B or C pancreatic fistula. Biochemical leak
according to the new definition (International Study Group on Pancreatic Surgery)
was observed in four patients (23.5%). No mortality was observed.
CONCLUSION
: Early results of this technique confirm
that it is simple, reliable, easy to perform, and easy to learn. This technique
is useful to reduce the incidence of pancreatic fistula after
pancreatoduodenectomy.
PMID- 29340551
TI - MINI-GASTRIC BYPASS: DESCRIPTION OF THE TECHNIQUE AND PRELIMINARY RESULTS.
AB - BACKGROUND : In recent years, a surgical technique known as single-anastomosis
gastric bypass or mini-gastric bypass has been developed. Its frequency of
performance has increased considerably in the current decade. AIM : To describe
the mini-gastric bypass technique, its implementation and preliminary results in
a university hospital. METHODS : This is an ongoing prospective trial to evaluate
the long-term effects of mini-gastric bypass. The main features of the operation
were: a gastric pouch with about 15-18 cm (50-150 ml) with a gastroenteric
anastomosis in the pre-colic isoperistaltic loop 200 cm from the duodenojejunal
angle (biliopancreatic loop). RESULTS : Seventeen individuals have undergone
surgery. No procedure needed to be converted to open approach. The overall 30-day
morbidity was 5.9% (one individual had intestinal obstruction caused by
adhesions). There was no mortality. CONCLUSION : Mini-gastric bypass is a
feasible and safe bariatric surgical procedure.
PMID- 29340552
TI - SINGLE ANASTOMOSIS GASTRIC BYPASS (ONE ANASTOMOSIS GASTRIC BYPASS OR MINI GASTRIC
BYPASS): THE EXPERIENCE WITH BILLROTH II MUST BE CONSIDERED AND IS A CHALLENGE
FOR THE NEXT YEARS.
AB - INTRODUCTION: Single anastomosis gastric bypass (one anastomosis gastric bypass
or mini-gastric bypass) has been presented as an option of surgical treatment for
obese patients in order to reduce operation time and avoiding eventual
postoperative complications after Roux-en-Y gastric bypass.The main late
complication could be related to bile reflux. AIM: To report the experiences
published after Billroth II anastomosis and its adverse effects regarding
symptoms and damage on the gastric and esophageal mucosa . METHOD: For data
recollection Medline, Pubmed, Scielo and Cochrane database were accessed, giving
a total of 168 papers being chosen 57 of them. RESULTS: According the reported
results during open era surgery for peptic disease and more recent results for
gastric cancer surgery, bile reflux and its consequences are more frequent after
Billroth II operation compared to Roux-en-Y gastrojejunal anastomosis.
CONCLUSION: These findings must be considered for the indication of bariatric
surgery.
PMID- 29340553
TI - HEPATOCELLULAR CARCINOMA: DIAGNOSIS AND OPERATIVE MANAGEMENT.
AB - INTRODUCTION: Hepatocellular carcinoma is an aggressive malignant tumor with high
lethality. AIM: To review diagnosis and management of hepatocellular carcinoma.
METHODS: Literature review using web databases Medline/PubMed. RESULTS:
Hepatocellular carcinoma is a common complication of hepatic cirrhosis. Chronic
viral hepatitis B and C also constitute as risk factors for its development. In
patients with cirrhosis, hepatocelular carcinoma usually rises upon malignant
transformation of a dysplastic regenerative nodule. Differential diagnosis with
other liver tumors is obtained through computed tomography scan with intravenous
contrast. Magnetic resonance may be helpful in some instances. The only
potentially curative treatment for hepatocellular carcinoma is tumor resection,
which may be performed through partial liver resection or liver transplantation.
Only 15% of all hepatocellular carcinomas are amenable to operative treatment.
Patients with Child C liver cirrhosis are not amenable to partial liver
resections. The only curative treatment for hepatocellular carcinomas in patients
with Child C cirrhosis is liver transplantation. In most countries, only patients
with hepatocellular carcinoma under Milan Criteria are considered candidates to a
liver transplant. CONCLUSION: Hepatocellular carcinoma is potentially curable if
discovered in its initial stages. Medical staff should be familiar with
strategies for early diagnosis and treatment of hepatocellular carcinoma as a way
to decrease mortality associated with this malignant neoplasm.
PMID- 29340554
TI - FUNDOPLICATION CONVERSION IN ROUX-EN-Y GASTRIC BYPASS FOR CONTROL OF OBESITY AND
GASTROESOPHAGEAL REFLUX: SYSTEMATIC REVIEW.
AB - INTRODUCTION : Obesity is related with higher incidence of gastroesophageal
reflux disease. Antireflux surgery has inadequate results when associated with
obesity, due to migration and/or subsequent disruption of antireflux wrap.
Gastric bypass, meanwhile, provides good control of gastroesophageal reflux.
OBJECTIVE: To evaluate the technical difficulty in performing gastric bypass in
patients previously submitted to antireflux surgery, and its effectiveness in
controlling gastroesophageal reflux. METHODS: Literature review was conducted
between July to October 2016 in Medline database, using the following search
strategy: ("Gastric bypass" OR "Roux-en-Y") AND ("Fundoplication" OR "Nissen ')
AND ("Reoperation" OR "Reoperative" OR "Revisional" OR "Revision" OR
"Complications"). RESULTS: Were initially classified 102 articles; from them at
the end only six were selected by exclusion criteria. A total of 121 patients
were included, 68 women. The mean preoperative body mass index was 37.17 kg/m2
and age of 52.60 years. Laparoscopic Nissen fundoplication was the main prior
antireflux surgery (70.58%). The most common findings on
esophagogastroduodenoscopy were esophagitis (n=7) and Barrett's esophagus (n=6);
the most common early complication was gastric perforation (n=7), and most common
late complication was stricture of gastrojejunostomy (n=9). Laparoscopic gastric
bypass was performed in 99 patients, with an average time of 331 min. Most
patients had complete remission of symptoms and efficient excess weight loss.
CONCLUSION: Although technically more difficult, with higher incidence of
complications, gastric bypass is a safe and effective option for controlling
gastroesophageal reflux in obese patients previously submitted to antireflux
surgery, with the added benefit of excess weight loss.
PMID- 29340556
TI - AMYAND'S HERNIA: OUR EPERIENCE AND REVIEW OF LITERATURE.
PMID- 29340555
TI - THE ROLE OF THE SLEEVE GASTRECTOMY AND THE MANAGEMENT OF TYPE 2 DIABETES.
AB - BACKGROUND : Currently, bariatric surgery has promoted weight loss and improved
glycemic control in obese patients through different techniques, including
vertical sleeve gastrectomy. AIM : Present and update the different vertical
sleeve gastrectomy ways of action, both in the treatment of obesity and diabetes,
approaching its potential effect on gastrointestinal physiology, as well as the
benefits achieved by this manipulation. METHODS : Pubmed database search was used
crossing the headings: obesity, type 2 diabetes and sleeve gastrectomy. RESULTS :
Published data have shown that short-term weight loss tends to be higher in
patients undergoing vertical sleeve gastrectomy compared to Roux-en-Y gastric
bypass. In relation to glycemic control, the procedure demonstrated remission of
diabetes in up to 60% after one year of surgery. After three years, however,
differences in remission rate between surgical and clinical group was not
observed, questioning the durability of the technical in a long-term. CONCLUSION
: Despite showing good results, both in the weight loss and co-morbidities,
conflicting results reinforce the need for more studies to prove the efficiency
of the vertical sleeve gastrectomy as well as to understand its action about the
molecular mechanisms involved in the disease.
PMID- 29340557
TI - AN UNUSUAL CAUSE OF ACUTE ABDOMEN: SPLENIC INFARCTION.
PMID- 29340558
TI - LAPAROSCOPIC ABDOMINOPERINEAL RESECTION WITH SACRECTOMY: TECHNICAL DETAILS AND
PITFALLS.
PMID- 29340559
TI - Serial Magnetic Resonance Imaging Changes in a Patient With Late-Onset Cobalamin
C Disease With a Misdiagnosis of Metachromatic Leukodystrophy.
PMID- 29340560
TI - Physician-Scientist Career Awards and a Dilemma: National Institute of Child
Health and Human Development K Awards-Individual, Institutional, or National?
PMID- 29340561
TI - Generic Substitution Rates of Oral Contraceptives and Associated Out-of-Pocket
Cost Savings Between January 2010 and December 2014.
PMID- 29340563
TI - Citation Errors in Figure 2.
PMID- 29340562
TI - Medicare Spending and Potential Savings on Brand-Name Drugs With Available
Generic Substitutes Excluded by 2 Large Pharmacy Benefit Managers, 2012 Through
2015.
PMID- 29340565
TI - Using Chaplains to Facilitate Advance Care Planning in Medical Practice.
PMID- 29340564
TI - Changes in Health Care Use Associated With the Introduction of Hospital Global
Budgets in Maryland.
AB - Importance: In 2014, the State of Maryland placed the majority of its hospitals
under all-payer global budgets for inpatient, hospital outpatient, and emergency
department care. Goals of the program included reducing unnecessary hospital
utilization and encouraging greater use of primary care. Objective: To compare
changes in hospital and primary care use through the first 2 years of Maryland's
hospital global budget program among fee-for-service Medicare beneficiaries in
Maryland vs matched control areas. Design, Setting, and Participants: We matched
8 Maryland counties (94 967 beneficiaries) with hospitals in the program to 27
non-Maryland control counties (206 389 beneficiaries). Using difference-in
differences analysis, we compared changes in hospital and primary care use in
Maryland vs the control counties from before (2009-2013) to after (2014-2015) the
payment change, using 2 different assumptions. First, we assumed that
preintervention differences between Maryland and the control counties would have
remained constant past 2014 had Maryland not implemented global budgets (parallel
trend assumption). Second, we assumed that differences in preintervention trends
would have continued without the payment change (differential trend assumption).
Main Outcomes and Measures: Hospital stays (defined as admissions and observation
stays); return hospital stays within 30 days of a prior hospital stay; emergency
department visits that did not result in admission; price-standardized hospital
outpatient department (HOPD) utilization; and visits with primary care physicians
(overall and within 7 days of a hospital stay). Results: We matched 8 Maryland
counties with hospitals in the program (94 967 beneficiaries; 41.8% male; mean
[SD] age, 72.3 [12.2] years) to 27 non-Maryland control counties (206 389
beneficiaries; 42.8% male; mean [SD] age, 71.7 [12.5] years). Assuming parallel
trends, we estimated a differential change in Maryland of -0.47 annual hospital
stays per 100 beneficiaries (95% CI, -1.65 to 0.72; P = .43) from the
preintervention period (2009-2013) to 2015, but assuming differential trends, we
estimated a differential change in Maryland of -1.24 stays per 100 beneficiaries
(95% CI, -2.46 to -0.02; P = .047). Assuming parallel trends, we found a
significant increase in primary care visits (+10.6 annual visits/100
beneficiaries; 95% CI, 4.6 to 16.6 annual visits/100 beneficiaries; P = .001),
but assuming differential trends, we found no change (-0.8 visits/100
beneficiaries; 95% CI, -10.6 to 9.0 visits/100 beneficiaries; P = .87). Comparing
estimates with both trend assumptions, we found no consistent changes in
emergency department visits, return hospital stays, HOPD use, or
posthospitalization primary care visits associated with Maryland's program.
Conclusions and Relevance: We did not find consistent evidence that Maryland's
hospital global budget program was associated with reductions in hospital use or
increases in primary care visits among fee-for-service Medicare beneficiaries
after 2 years. Evaluations over longer periods should be pursued.
PMID- 29340566
TI - Annals for Educators - 16 January 2018.
PMID- 29340567
TI - Annals for Hospitalists - 16 January 2018.
PMID- 29340568
TI - Maryland's All-Payer Health Reform-A Promising Work in Progress.
PMID- 29340570
TI - Name and Characteristics of National Institutes of Health R01-Funded Pediatric
Physician-Scientists: Hope and Challenges for the Vanishing Pediatric Physician
Scientists.
PMID- 29340569
TI - Associations of the Top 20 Alzheimer Disease Risk Variants With Brain
Amyloidosis.
AB - Importance: Late-onset Alzheimer disease (AD) is highly heritable. Genome-wide
association studies have identified more than 20 AD risk genes. The precise
mechanism through which many of these genes are associated with AD remains
unknown. Objective: To investigate the association of the top 20 AD risk variants
with brain amyloidosis. Design, Setting, and Participants: This study analyzed
the genetic and florbetapir F 18 data from 322 cognitively normal control
individuals, 496 individuals with mild cognitive impairment, and 159 individuals
with AD dementia who had genome-wide association studies and 18F-florbetapir
positron emission tomographic data from the Alzheimer's Disease Neuroimaging
Initiative (ADNI), a prospective, observational, multisite tertiary center
clinical and biomarker study. This ongoing study began in 2005. Main Outcomes and
Measures: The study tested the association of AD risk allele carrier status
(exposure) with florbetapir mean standard uptake value ratio (outcome) using
stepwise multivariable linear regression while controlling for age, sex, and
apolipoprotein E epsilon4 genotype. The study also reports on an exploratory 3
dimensional stepwise regression model using an unbiased voxelwise approach in
Statistical Parametric Mapping 8 with cluster and significance thresholds at 50
voxels and uncorrected P < .01. Results: This study included 977 participants
(mean [SD] age, 74 [7.5] years; 535 [54.8%] male and 442 [45.2%] female) from the
ADNI-1, ADNI-2, and ADNI-Grand Opportunity. The adenosine triphosphate-binding
cassette subfamily A member 7 (ABCA7) gene had the strongest association with
amyloid deposition (chi2 = 8.38, false discovery rate-corrected P < .001), after
apolioprotein E epsilon4. Significant associations were found between ABCA7 in
the asymptomatic and early symptomatic disease stages, suggesting an association
with rapid amyloid accumulation. The fermitin family homolog 2 (FERMT2) gene had
a stage-dependent association with brain amyloidosis (FERMT2 * diagnosis chi2 =
3.53, false discovery rate-corrected P = .05), which was most pronounced in the
mild cognitive impairment stage. Conclusions and Relevance: This study found an
association of several AD risk variants with brain amyloidosis. The data also
suggest that AD genes might differentially regulate AD pathologic findings across
the disease stages.
PMID- 29340572
TI - Overuse of Percutaneous Coronary Interventions.
PMID- 29340571
TI - Comparison of Physician Visual Assessment With Quantitative Coronary Angiography
in Assessment of Stenosis Severity in China.
AB - Importance: Although physician visual assessment (PVA) of stenosis severity is a
standard clinical practice to support decisions for coronary revascularization,
there are concerns about its accuracy. Objective: To compare PVA with
quantitative coronary angiography (QCA) as a means of assessing stenosis severity
among patients undergoing percutaneous coronary intervention (PCI) in China.
Design, Setting, and Participants: A cross-sectional study (2012-2013) of a
random subset of 1295 patients from the China Patient-centered Evaluative
Assessment of Cardiac Events (PEACE) Prospective PCI Study was carried out. The
PEACE Prospective PCI study recruited a consecutive sample of patients undergoing
PCI at 35 hospitals in 18 provinces of China. The coronary angiograms of this
subset of participants were reviewed using QCA by 2 independent core laboratories
blinded to PVA readings. Main Outcomes and Measures: Differences between PVA and
QCA assessments of stenosis severity for lesions for which PCI was performed and
variation of these differences among hospitals and physicians, stratified by the
diagnosis of acute myocardial infarction (AMI). Results: In patients without AMI,
the mean (SD) age was 62 (10) years, and 217 (31.5%) were women; in patients with
AMI, the mean (SD) age was 60 (11) years, and 153 (25.2%) were women. The mean
(SD) percent diameter stenosis by PVA was 16.0% (11.5%) greater than that by QCA
in patients without AMI and 10.2% (12.3%) in those with AMI (P < .001 for both
comparisons). In patients without AMI, of 837 lesions with 70% or more stenosis
by PVA, 427 (50.6%) were less than 70% by QCA; in patients with AMI, similar
patterns were observed to a lesser extent. Among patients without AMI, only 4
(0.47%) lesions were additionally assessed with fractional flow reserve. Among 30
hospitals, the difference between PVA and QCA readings of stenosis severity
varied from 7.6% (95% CI, 0.4%-14.7%) to 21.3% (95% CI, 17.1%-24.9%) among non
AMI patients. Across 57 physicians, this difference varied from 6.9% (95% CI,
1.4%-15.3%) to 26.4% (95% CI, 21.5%-31.4%). Conclusions and Relevance: For
coronary lesions treated with PCI in China, PVA reported substantially higher
readings of stenosis severity than QCA, with large variation across hospitals and
physicians. These findings highlight the need to improve the accuracy of
information used to guide treatment decisions in catheterization laboratories.
PMID- 29340573
TI - Challenges for Today's Pediatric Physician-Scientists.
PMID- 29340575
TI - The Fragile State of the National Institutes of Health Pediatric Research
Portfolio, 1992-2015: Doing More With Less?
AB - In this article, we examine the status of the National Institutes of Health (NIH)
pediatric research portfolio between start of federal fiscal year (FY) 1992 and
end of FY 2015. The NIH experienced the greatest mean annual growth rate during
the "doubling era" (FY 1998-2003): both the NIH budget (13.5%) and pediatric
research portfolios (11.5%) increased annually by double digits. However, in the
"postdoubling" era (FY 2004-2009), both the NIH (2.0%) and pediatric (-0.2%) mean
annual growth rates decreased dramatically. In the most recent era (FY 2010
2015), the NIH mean annual growth rate has been flat (-0.1%) and pediatric
research funding has posted very modest gains (3.5%) without accounting for 1
time increases under the 2009 American Recovery and Reinvestment Act. We offer
recommendations to protect against further erosion of the pediatric research
portfolio because continuation of these trends will have a negative effect on the
health of children during their childhood and as adults. As capacity to conduct
basic and applied research is further constrained, it will be a challenge for
pediatric researchers to do more with less and less.
PMID- 29340574
TI - Effect of General Anesthesia and Conscious Sedation During Endovascular Therapy
on Infarct Growth and Clinical Outcomes in Acute Ischemic Stroke: A Randomized
Clinical Trial.
AB - Importance: Endovascular therapy (EVT) is the standard of care for select
patients who had a stroke caused by a large vessel occlusion in the anterior
circulation, but there is uncertainty regarding the optimal anesthetic approach
during EVT. Observational studies suggest that general anesthesia (GA) is
associated with worse outcomes compared with conscious sedation (CS). Objective:
To examine the effect of type of anesthesia during EVT on infarct growth and
clinical outcome. Design, Setting, and Participants: The General or Local
Anesthesia in Intra Arterial Therapy (GOLIATH) trial was a single-center
prospective, randomized, open-label, blinded end-point evaluation that enrolled
patients from March 12, 2015, to February 2, 2017. Although the trial screened
1501 patients, it included 128 consecutive patients with acute ischemic stroke
caused by large vessel occlusions in the anterior circulation within 6 hours of
onset; 1372 patients who did not fulfill inclusion criteria and 1 who did not
provide consent were excluded. Primary analysis was unadjusted and according to
the intention-to-treat principle. Interventions: Patients were randomized to
either the GA group or the CS group (1:1 allocation) before EVT. Main Outcomes
and Measures: The primary end point was infarct growth between magnetic resonance
imaging scans performed before EVT and 48 to 72 hours after EVT. The hypothesis
formulated before data collection was that patients who were under CS would have
less infarct growth. Results: Of 128 patients included in the trial, 65 were
randomized to GA, and 63 were randomized to CS. For the entire cohort, the mean
(SD) age was 71.4 (11.4) years, and 62 (48.4%) were women. Baseline demographic
and clinical variables were balanced between the GA and CS treatment arms. The
median National Institutes of Health Stroke Scale score was 18 (interquartile
range [IQR], 14-21). Four patients (6.3%) in the CS group were converted to the
GA group. Successful reperfusion was significantly higher in the GA arm than in
the CS arm (76.9% vs 60.3%; P = .04). The difference in the volume of infarct
growth among patients treated under GA or CS did not reach statistical
significance (median [IQR] growth, 8.2 [2.2-38.6] mL vs 19.4 [2.4-79.0] mL; P =
.10). There were better clinical outcomes in the GA group, with an odds ratio for
a shift to a lower modified Rankin Scale score of 1.91 (95% CI, 1.03-3.56).
Conclusions and Relevance: For patients who underwent thrombectomy for acute
ischemic stroke caused by large vessel occlusions in the anterior circulation, GA
did not result in worse tissue or clinical outcomes compared with CS. Trial
Registration: clinicaltrials.gov Identifier: NCT02317237.
PMID- 29340576
TI - Association of National Institute of Child Health and Human Development Career
Development Awards With Subsequent Research Project Grant Funding.
AB - Importance: Investing in the next generation of researchers is essential, as
recently highlighted in the 21st Century Cures Act. From its inception, the
Eunice Kennedy Shriver National Institute of Child Health and Human Development
(NICHD) has supported training and career development to ensure a robust pipeline
of investigators who are prepared to lead their respective fields of inquiry. In
recent years, the NICHD has emphasized institutional over individual training
awards to a greater degree than many other National Institutes of Health
institutes of similar size. Objective: To evaluate the success of individuals
supported by NICHD career development and training awards, as measured by
subsequent application and receipt of independent National Institutes of Health
research project grant funding. Design, Setting, and Participants: This
retrospective cohort study identified 417 physician-scholars who were supported
by NICHD career development awards between October 1, 1999, and September 30,
2001. This period was selected to allow adequate follow-up of research project
grant applications and funding. Among these physician-scholars, 355 met inclusion
criteria. Main Outcomes and Measures: The primary outcomes were the numbers of
research project grant applications submitted and, of these, the numbers that
were successfully funded. Results: Among 355 physician-scientists, scholars who
had an MD degree only and received a K award or both an individual K award and
institutional K12 support were more likely than those who received only K12
support (individual K only vs institutional K12 only: odds ratio [OR], 4.86; 95%
CI, 1.83-13.62; both K and K12 vs K12 only: OR, 3.19; 95% CI, 1.46-7.10) to apply
for subsequent project grant funding (88.0% vs 82.8% vs 60.1%, respectively; P <
.001) and to receive it (60.0% vs 60.9% vs 32.9%, respectively; P < .001). For
physicians with both MD and PhD degrees, neither application nor funding rates
were statistically significantly different whether their career development was
supported by individual or institutional awards. Conclusions and Relevance:
Physician-scholars are more likely to apply for and receive a National Institutes
of Health research grant if they are trained on an individual career development
award, with or without an institutional training award. Based on the data, the
NICHD intends to provide a greater proportion of its career development fund
allocation to individual awards. The NICHD recognizes the importance of
institutional awards and will continue to support them. The NICHD remains
committed to training and intends to maintain its investment in training and
career development awards going forward.
PMID- 29340577
TI - Lactation Duration and Progression to Diabetes in Women Across the Childbearing
Years: The 30-Year CARDIA Study.
AB - Importance: Lactation duration has shown weak protective associations with
incident diabetes (3%-15% lower incidence per year of lactation) in older women
based solely on self-report of diabetes, studies initiated beyond the
reproductive period are vulnerable to unmeasured confounding or reverse causation
from antecedent biochemical risk status, perinatal outcomes, and behaviors across
the childbearing years. Objective: To evaluate the association between lactation
and progression to diabetes using biochemical testing both before and after
pregnancy and accounting for prepregnancy cardiometabolic measures, gestational
diabetes (GD), and lifestyle behaviors. Design, Setting, and Participants: For
this US multicenter, community-based 30-year prospective cohort study, there were
1238 women from the Coronary Artery Risk Development in Young Adults (CARDIA)
study of young black and white women ages 18 to 30 years without diabetes at
baseline (1985-1986) who had 1 or more live births after baseline, reported
lactation duration, and were screened for diabetes up to 7 times during 30 years
after baseline (1986-2016). Exposures: Time-dependent lactation duration
categories (none, >0 to 6 months, >6 to <12 months, and >=12 months) across all
births since baseline through 30 years. Main Outcomes and Measures: Diabetes
incidence rates per 1000 person-years and adjusted relative hazards (RH) with
corresponding 95% CIs, as well as proportional hazards regression models adjusted
for biochemical, sociodemographic, and reproductive risk factors, as well as
family history of diabetes, lifestyle, and weight change during follow-up.
Results: Overall 1238 women were included in this analysis (mean [SD] age, 24.2
[3.7] years; 615 black women). There were 182 incident diabetes cases during 27
598 person-years for an overall incidence rate of 6.6 cases per 1000 person-years
(95% CI, 5.6-7.6); and rates for women with GD and without GD were 18.0 (95% CI,
13.3-22.8) and 5.1 (95% CI, 4.2-6.0), respectively (P for difference < .001).
Lactation duration showed a strong, graded inverse association with diabetes
incidence: adjusted RH for more than 0 to 6 months, 0.75 (95% CI, 0.51-1.09);
more than 6 months to less than 12 months, 0.52 (95% CI, 0.31-0.87), and 12
months or more 0.53 (0.29-0.98) vs none (0 days) (P for trend = .01). There was
no evidence of effect modification by race, GD, or parity. Conclusions and
Relevance: This study provides longitudinal biochemical evidence that lactation
duration is independently associated with lower incidence of diabetes. Further
investigation is required to elucidate mechanisms that may explain this
relationship.
PMID- 29340578
TI - Clinical recommendations for high altitude exposure of individuals with pre
existing cardiovascular conditions: A joint statement by the European Society of
Cardiology, the Council on Hypertension of the European Society of Cardiology,
the European Society of Hypertension, the International Society of Mountain
Medicine, the Italian Society of Hypertension and the Italian Society of Mountain
Medicine.
AB - Take home figureAdapted from Bartsch and Gibbs2 Physiological response to
hypoxia. Life-sustaining oxygen delivery, in spite of a reduction in the partial
pressure of inhaled oxygen between 25% and 60% (respectively at 2500 m and 8000
m), is ensured by an increase in pulmonary ventilation, an increase in cardiac
output by increasing heart rate, changes in vascular tone, as well as an increase
in haemoglobin concentration. BP, blood pressure; HR, heart rate; PaCO2, partial
pressure of arterial carbon dioxide.
PMID- 29340579
TI - Extracorporeal life support in thoracic surgery.
PMID- 29340580
TI - Population Specific Biomarkers of Human Aging: A Big Data Study Using South
Korean, Canadian, and Eastern European Patient Populations.
AB - Accurate and physiologically meaningful biomarkers for human aging are key to
assessing antiaging therapies. Given ethnic differences in health, diet,
lifestyle, behavior, environmental exposures, and even average rate of biological
aging, it stands to reason that aging clocks trained on datasets obtained from
specific ethnic populations are more likely to account for these potential
confounding factors, resulting in an enhanced capacity to predict chronological
age and quantify biological age. Here, we present a deep learning-based
hematological aging clock modeled using the large combined dataset of Canadian,
South Korean, and Eastern European population blood samples that show increased
predictive accuracy in individual populations compared to population specific
hematologic aging clocks. The performance of models was also evaluated on
publicly available samples of the American population from the National Health
and Nutrition Examination Survey (NHANES). In addition, we explored the
association between age predicted by both population specific and combined
hematological clocks and all-cause mortality. Overall, this study suggests (a)
the population specificity of aging patterns and (b) hematologic clocks predicts
all-cause mortality. The proposed models were added to the freely-available
Aging.AI system expanding the range of tools for analysis of human aging.
PMID- 29340581
TI - Gene Turnover and Diversification of the alpha- and beta-Globin Gene Families in
Sauropsid Vertebrates.
AB - The genes that encode the alpha- and beta-chain subunits of vertebrate hemoglobin
have served as a model system for elucidating general principles of gene family
evolution, but little is known about patterns of evolution in amniotes other than
mammals and birds. Here, we report a comparative genomic analysis of the alpha-
and beta-globin gene clusters in sauropsids (archosaurs and nonavian reptiles).
The objectives were to characterize changes in the size and membership
composition of the alpha- and beta-globin gene families within and among the
major sauropsid lineages, to reconstruct the evolutionary history of the
sauropsid alpha- and beta-globin genes, to resolve orthologous relationships, and
to reconstruct evolutionary changes in the developmental regulation of gene
expression. Our comparisons revealed contrasting patterns of evolution in the
unlinked alpha- and beta-globin gene clusters. In the alpha-globin gene cluster,
which has remained in the ancestral chromosomal location, evolutionary changes in
gene content are attributable to the differential retention of paralogous gene
copies that were present in the common ancestor of tetrapods. In the beta-globin
gene cluster, which was translocated to a new chromosomal location, evolutionary
changes in gene content are attributable to differential gene gains (via lineage
specific duplication events) and gene losses (via lineage-specific deletions and
inactivations). Consequently, all major groups of amniotes possess unique
repertoires of embryonic and postnatally expressed beta-type globin genes that
diversified independently in each lineage. These independently derived beta-type
globins descend from a pair of tandemly linked paralogs in the most recent common
ancestor of sauropsids.
PMID- 29340582
TI - Immune-Related Transcriptional Responses to Parasitic Infection in a Naturally
Inbred Fish: Roles of Genotype and Individual Variation.
AB - Parasites are strong drivers of evolutionary change and the genetic variation of
both host and parasite populations can co-evolve as a function of parasite
virulence and host resistance. The role of transcriptome variation in specific
interactions between host and parasite genotypes has been less studied and can be
confounded by differences in genetic variation. We employed two naturally inbred
lines of a self-fertilizing fish to estimate the role of host genotype in the
transcriptome response to parasite infection using RNA-seq. In addition, we
targeted several differentially expressed immune-related genes to further
investigate the relative role of individual variation in the immune response
using RT-qPCR, taking advantage of the genomic uniformity of the self-fertilizing
lines. We found significant differences in gene expression between lines in
response to infection both in the transcriptome and in individual gene RT-qPCR
analyses. Individual RT-qPCR analyses of gene expression identified significant
variance differences between lines for six genes but only for three genes between
infected and control fish. Our results indicate that although the genetic
background plays an important role in the transcriptome response to parasites, it
cannot fully explain individual differences within genetically homogeneous lines,
which can be important for determining the response to parasites.
PMID- 29340583
TI - Functional analysis of the Helicobacter pullorum N-linked protein glycosylation
system.
AB - N-linked protein glycosylation systems operate in species from all three domains
of life. The model bacterial N-linked glycosylation system from Campylobacter
jejuni is encoded by pgl genes present at a single chromosomal locus. This gene
cluster includes the pglB oligosaccharyltransferase responsible for transfer of
glycan from lipid carrier to protein. Although all genomes from species of the
Campylobacter genus contain a pgl locus, among the related Helicobacter genus
only three evolutionarily related species (H. pullorum, H. canadensis and H.
winghamensis) potentially encode N-linked protein glycosylation systems.
Helicobacter putative pgl genes are scattered in five chromosomal loci and
include two putative oligosaccharyltransferase-encoding pglB genes per genome. We
have previously demonstrated the in vitro N-linked glycosylation activity of H.
pullorum resulting in transfer of a pentasaccharide to a peptide at asparagine
within the sequon (D/E)XNXS/T. In this study, we identified the first H. pullorum
N-linked glycoprotein, termed HgpA. Production of histidine-tagged HgpA in the
background of insertional knockout mutants of H. pullorum pgl/wbp genes followed
by analysis of HgpA glycan structures demonstrated the role of individual gene
products in the PglB1-dependent N-linked protein glycosylation pathway.
Glycopeptide purification by zwitterionic-hydrophilic interaction liquid
chromatography coupled with tandem mass spectrometry identified six glycosites
from five H. pullorum proteins, which was consistent with proteins reactive with
a polyclonal antiserum generated against glycosylated HgpA. This study
demonstrates functioning of a H. pullorum N-linked general protein glycosylation
system.
PMID- 29340585
TI - Spinal Tuberculosis: Clinicoradiological Findings in 274 Patients.
AB - Background: Mycobacterium tuberculosis is a major cause of myelopathy and
radiculopathy in settings with a high prevalence of tuberculosis/human
immunodeficiency virus (HIV) coinfection. However, a paucity of publications
exists on the spectrum of neurological and magnetic resonance (MR) imaging
findings of spinal tuberculosis in these populations. Methods: We conducted a
retrospective study of adults with spinal tuberculosis at a referral center in
South Africa for patients with spinal disease without bony involvement seen at
plain film radiography. We report the clinical, laboratory and spinal MR imaging
findings, compare HIV-infected and HIV-uninfected patients, and correlate
clinical and cerebrospinal fluid findings with those of MR imaging. Results: Of
274 patients, 209 (76%) were HIV infected and 49 (18%) were HIV uninfected.
Radiculomyelitis occurred in 77% (n = 210), and spondylitis in 39% (n = 106).
Subdural abscess (n = 42) and intramedullary tuberculoma (n = 33) were common. In
24% of HIV-infected and 14% of HIV-uninfected patients, spinal disease manifested
as a paradoxical tuberculosis reaction, frequently following tuberculous
meningitis. The triad of neurological deficit, fever, and back pain was similar
in patients with spondylitis (24%), epi/subdural abscess without bony disease
(14%), meningoradiculitis (17%), and isolated myelitis (17%) . Conclusions:
Radiculomyelitis is a common manifestation of spinal tuberculosis in settings
with high tuberculosis/HIV prevalence, often presenting as a paradoxical
reaction. We describe a high frequency of rarely reported spinal tuberculosis
manifestations, suggesting that these are more common than implied by the
literature.
PMID- 29340586
TI - Data Sharing.
PMID- 29340584
TI - Long-interval intracortical inhibition as biomarker for epilepsy: a transcranial
magnetic stimulation study.
AB - Cortical excitability, as measured by transcranial magnetic stimulation combined
with electromyography, is a potential biomarker for the diagnosis and follow-up
of epilepsy. We report on long-interval intracortical inhibition data measured in
four different centres in healthy controls (n = 95), subjects with refractory
genetic generalized epilepsy (n = 40) and with refractory focal epilepsy (n =
69). Long-interval intracortical inhibition was measured by applying two supra
threshold stimuli with an interstimulus interval of 50, 100, 150, 200 and 250 ms
and calculating the ratio between the response to the second (test stimulus) and
to the first (conditioning stimulus). In all subjects, the median response ratio
showed inhibition at all interstimulus intervals. Using a mixed linear-effects
model, we compared the long-interval intracortical inhibition response ratios
between the different subject types. We conducted two analyses; one including
data from the four centres and one excluding data from Centre 2, as the methods
in this centre differed from the others. In the first analysis, we found no
differences in long-interval intracortical inhibition between the different
subject types. In all subjects, the response ratios at interstimulus intervals
100 and 150 ms showed significantly more inhibition than the response ratios at
50, 200 and 250 ms. Our second analysis showed a significant interaction between
interstimulus interval and subject type (P = 0.0003). Post hoc testing showed
significant differences between controls and refractory focal epilepsy at
interstimulus intervals of 100 ms (P = 0.02) and 200 ms (P = 0.04). There were no
significant differences between controls and refractory generalized epilepsy
groups or between the refractory generalized and focal epilepsy groups. Our
results do not support the body of previous work that suggests that long-interval
intracortical inhibition is significantly reduced in refractory focal and genetic
generalized epilepsy. Results from the second analysis are even in sharper
contrast with previous work, showing inhibition in refractory focal epilepsy at
200 ms instead of facilitation previously reported. Methodological differences,
especially shorter intervals between the pulse pairs, may have contributed to our
inability to reproduce previous findings. Based on our results, we suggest that
long-interval intracortical inhibition as measured by transcranial magnetic
stimulation and electromyography is unlikely to have clinical use as a biomarker
of epilepsy.
PMID- 29340587
TI - Subclinical device-detected atrial fibrillation and stroke risk: a systematic
review and meta-analysis.
AB - Aims: To determine stroke risk in subclinical atrial fibrillation (AF) and
temporal association between subclinical AF and stroke. Methods and results:
Pubmed/Embase was searched for studies reporting stroke in subclinical AF in
patients with cardiac implantable electronic devices (CIEDs). After exclusions,
11 studies were analysed. Of these seven studies reported prevalence of
subclinical AF, two studies reported association between subclinical and clinical
AF, seven studies reported stroke risk in subclinical AF, and five studies
reported temporal relationship between subclinical AF and stroke. Subclinical AF
was noted after CIEDs implant in 35% [interquartile range (IQR) 34-42] of
unselected patients with pacing indication over 1-2.5 years. The definition and
cut-off duration (for stroke risk) of subclinical AF varied across studies.
Subclinical AF was strongly associated with clinical AF (OR 5.7, 95% CI 4.0-8.0,
P < 0.001, I2 = 0%). The annual stroke rate in patients with subclinical AF >
defined cut-off duration was 1.89/100 person-year (95% CI 1.02-3.52) with 2.4
fold (95% CI 1.8-3.3, P < 0.001, I2 = 0%) increased risk of stroke as compared to
patients with subclinical AF < cut-off duration (absolute risk was 0.93/100
person-year). Three studies provided mean CHADS2 score. In these studies, with
mean CHADS2 score of 2.1 +/- 0.1, subclinical AF was associated with annual
stroke rate of 2.76/100 person-years (95% CI 1.46-5.23). After excluding patients
without AF, only 17% strokes occurred in presence of ongoing AF. Subclinical AF
was noted in 29% [IQR 8-57] within 30 days preceding stroke. Conclusion:
Subclinical AF strongly predicts clinical AF and is associated with elevated
absolute stroke risk albeit lower than risk described for clinical AF.
PMID- 29340589
TI - Risk prediction by non-invasive coronary imaging: we are not there yet!
PMID- 29340588
TI - Antimicrobial-Resistant Klebsiella pneumoniae Carriage and Infection in
Specialized Geriatric Care Wards Linked to Acquisition in the Referring Hospital.
AB - Background: Klebsiella pneumoniae is a leading cause of extended-spectrum beta
lactamase (ESBL)-producing hospital-associated infections, for which elderly
patients are at increased risk. Methods: We conducted a 1-year prospective cohort
study, in which a third of patients admitted to 2 geriatric wards in a
specialized hospital were recruited and screened for carriage of K. pneumoniae by
microbiological culture. Clinical isolates were monitored via the hospital
laboratory. Colonizing and clinical isolates were subjected to whole-genome
sequencing and antimicrobial susceptibility testing. Results: K. pneumoniae
throat carriage prevalence was 4.1%, rectal carriage 10.8%, and ESBL carriage
1.7%, and the incidence of K. pneumoniae infection was 1.2%. The isolates were
diverse, and most patients were colonized or infected with a unique phylogenetic
lineage, with no evidence of transmission in the wards. ESBL strains carried
blaCTX-M-15 and belonged to clones associated with hospital-acquired ESBL
infections in other countries (sequence type [ST] 29, ST323, and ST340). One also
carried the carbapenemase blaIMP-26. Genomic and epidemiological data provided
evidence that ESBL strains were acquired in the referring hospital. Nanopore
sequencing also identified strain-to-strain transmission of a blaCTX-M-15
FIBK/FIIK plasmid in the referring hospital. Conclusions: The data suggest the
major source of K. pneumoniae was the patient's own gut microbiome, but ESBL
strains were acquired in the referring hospital. This highlights the importance
of the wider hospital network to understanding K. pneumoniae risk and infection
prevention. Rectal screening for ESBL organisms on admission to geriatric wards
could help inform patient management and infection control in such facilities.
PMID- 29340591
TI - Interactions of Coccinella novemnotata (Coleoptera: Coccinellidae) and Coccinella
septempunctata (Coleoptera: Coccinellidae) While Foraging for Aphids.
AB - The importation and establishment of Coccinella septempunctata L. (Coleoptera:
Coccinellidae) in North America purportedly caused the displacement and local
extirpation of the native ninespotted lady beetle, Coccinella novemnotata Herbst
(Coleoptera: Coccinellidae), across most of its former range, and several reports
have shown that C. septempunctata maintains competitive advantages over C.
novemnotata. We investigated the role of aphid density on the retention time of
these two species on fava bean plants, and the effect of con- versus
heterospecific pairings of adult beetles on the foraging behavior of C.
novemnotata. We found that aphid density did not affect C. novemnotata's
retention time, but did affect the retention time of C. septempunctata, which
left plants without aphids significantly faster than C. novemnotata.
Additionally, C. septempunctata females left plants significantly faster than
their male counterparts, whereas we observed no difference between the two sexes
for C. novemnotata. Our test of pairs of beetles showed that C. novemnotata were
together on plants more frequently than conspecific pairs of C. septempunctata
and heterospecific pairs of beetles, and that all beetles were more likely to be
found together on the aphid-infested plant versus the non-infested plant
regardless of the pairs' composition. These results show that C. novemnotata
spend more time foraging for aphids when aphids are scarce compared with C.
septempunctata, and that C. novemnotata is less tolerant of occupying plants
inhabited by C. septempunctata versus a conspecific beetle, adding additional
mechanisms whereby C. septempunctata could outcompete C. novemnotata in the
field.
PMID- 29340592
TI - Neuroimmunomodulators in Neuroborreliosis and Lyme Encephalopathy.
AB - Background: Lyme encephalopathy, characterized by nonspecific neurobehavioral
symptoms including mild cognitive difficulties, may occur in patients with
systemic Lyme disease and is often mistakenly attributed to central nervous
system (CNS) infection. Identical symptoms occur in many inflammatory states,
possibly reflecting the effect of systemic immune mediators on the CNS. Methods:
Multiplex immunoassays were used to measure serum and cerebrospinal fluid (CSF)
cytokines in patients with or without Lyme disease to determine if there are
specific markers of active CNS infection (neuroborreliosis), or systemic
inflammatory mediators associated with neurobehavioral syndromes. Results: CSF
CXCL13 levels were elevated dramatically in confirmed neuroborreliosis (n = 8),
less so in possible neuroborreliosis (n = 11) and other neuroinflammatory
conditions (n = 44). Patients with Lyme (n = 63) or non-Lyme (n = 8)
encephalopathy had normal CSF findings, but had elevated serum levels of
interleukins 7, 17A, and 17F, thymic stromal lymphopoietin and macrophage
inflammatory protein-alpha. Conclusions: CSF CXCL13 is a sensitive and specific
marker of neuroborreliosis in individuals with Borrelia-specific intrathecal
antibody production. However, it does not distinguish individuals strongly
suspected of having neuroborreliosis, but lacking confirmatory intrathecal
antibodies, from those with other neuroinflammatory conditions. Patients with
mild cognitive symptoms occurring during acute Lyme disease, and/or after
appropriate treatment, have normal CSF but elevated serum levels of T-helper 17
markers and T-cell growth factors, which are also elevated in patients without
Lyme disease but with similar symptoms. In the absence of CSF abnormalities,
neurobehavioral symptoms appear to be associated with systemic inflammation, not
CNS infection or inflammation, and are not specific to Lyme disease.
PMID- 29340590
TI - Efficacy and Safety of Deep Brain Stimulation in Tourette Syndrome: The
International Tourette Syndrome Deep Brain Stimulation Public Database and
Registry.
AB - Importance: Collective evidence has strongly suggested that deep brain
stimulation (DBS) is a promising therapy for Tourette syndrome. Objective: To
assess the efficacy and safety of DBS in a multinational cohort of patients with
Tourette syndrome. Design, Setting, and Participants: The prospective
International Deep Brain Stimulation Database and Registry included 185 patients
with medically refractory Tourette syndrome who underwent DBS implantation from
January 1, 2012, to December 31, 2016, at 31 institutions in 10 countries
worldwide. Exposures: Patients with medically refractory symptoms received DBS
implantation in the centromedian thalamic region (93 of 163 [57.1%]), the
anterior globus pallidus internus (41 of 163 [25.2%]), the posterior globus
pallidus internus (25 of 163 [15.3%]), and the anterior limb of the internal
capsule (4 of 163 [2.5%]). Main Outcomes and Measures: Scores on the Yale Global
Tic Severity Scale and adverse events. Results: The International Deep Brain
Stimulation Database and Registry enrolled 185 patients (of 171 with available
data, 37 females and 134 males; mean [SD] age at surgery, 29.1 [10.8] years
[range, 13-58 years]). Symptoms of obsessive-compulsive disorder were present in
97 of 151 patients (64.2%) and 32 of 148 (21.6%) had a history of self-injurious
behavior. The mean (SD) total Yale Global Tic Severity Scale score improved from
75.01 (18.36) at baseline to 41.19 (20.00) at 1 year after DBS implantation (P <
.001). The mean (SD) motor tic subscore improved from 21.00 (3.72) at baseline to
12.91 (5.78) after 1 year (P < .001), and the mean (SD) phonic tic subscore
improved from 16.82 (6.56) at baseline to 9.63 (6.99) at 1 year (P < .001). The
overall adverse event rate was 35.4% (56 of 158 patients), with intracranial
hemorrhage occurring in 2 patients (1.3%), infection in 4 patients with 5 events
(3.2%), and lead explantation in 1 patient (0.6%). The most common stimulation
induced adverse effects were dysarthria (10 [6.3%]) and paresthesia (13 [8.2%]).
Conclusions and Relevance: Deep brain stimulation was associated with symptomatic
improvement in patients with Tourette syndrome but also with important adverse
events. A publicly available website on outcomes of DBS in patients with Tourette
syndrome has been provided.
PMID- 29340593
TI - The Clinical Utility of Methicillin-Resistant Staphylococcus aureus (MRSA) Nasal
Screening to Rule Out MRSA Pneumonia: A Diagnostic Meta-analysis With
Antimicrobial Stewardship Implications.
AB - Background: Recent literature has highlighted methicillin-resistant
Staphylococcus aureus (MRSA) nasal screening as a possible antimicrobial
stewardship program tool for avoiding unnecessary empiric MRSA therapy for
pneumonia, yet current guidelines recommend MRSA therapy based on risk factors.
The objective of this meta-analysis was to evaluate the diagnostic value of MRSA
nasal screening in MRSA pneumonia. Methods: PubMed and EMBASE were searched from
inception to November 2016 for English studies evaluating MRSA nasal screening
and development of MRSA pneumonia. Data analysis was performed using a bivariate
random-effects model to estimate pooled sensitivity, specificity, positive
predictive value (PPV), and negative predictive value (NPV). Results: Twenty-two
studies, comprising 5163 patients, met our inclusion criteria. The pooled
sensitivity and specificity of MRSA nares screen for all MRSA pneumonia types
were 70.9% and 90.3%, respectively. With a 10% prevalence of potential MRSA
pneumonia, the calculated PPV was 44.8%, and the NPV was 96.5%. The pooled
sensitivity and specificity for MRSA community-acquired pneumonia (CAP) and
healthcare-associated pneumonia (HCAP) were 85% and 92.1%, respectively. For CAP
and HCAP both the PPV and NPV increased, to 56.8% and 98.1%, respectively. In
comparison, for MRSA ventilated-associated pneumonia, the sensitivity,
specificity, PPV, and NPV were 40.3%, 93.7%, 35.7%, and 94.8%, respectively.
Conclusion: Nares screening for MRSA had a high specificity and NPV for ruling
out MRSA pneumonia, particularly in cases of CAP/HCAP. Based on the NPV, MRSA
nares screening is a valuable tool for AMS to streamline empiric antibiotic
therapy, especially among patients with pneumonia who are not colonized with
MRSA.
PMID- 29340595
TI - Clinical impact of rotor ablation in atrial fibrillation: a systematic review.
AB - Aims: Rotor mapping and ablation have gained favour over the recent years as an
emerging ablation strategy targeting drivers of atrial fibrillation (AF). Their
efficacy, however, has been a topic of great debate with variable outcomes across
centres. The aim of this study was to systematically review the recent medical
literature to determine the medium-term outcomes of rotor ablation in patients
with paroxysmal atrial fibrillation (PAF) and persistent atrial fibrillation
(PeAF). Methods and results: A systematic search of the contemporary scientific
literature (PubMed and EMBASE) was performed in August 2017. Only studies
assessing arrhythmia-free survival from rotor ablation of AF were included. We
used the random-effects model to assess the primary outcome of pooled medium-term
single-procedure AF-free survival for both PAF and PeAF. Success rates from
multiple procedures and complication rates were also examined. We included 11
observational studies (4 PAF and 10 PeAF) with a total of 556 patients (166 PAF
and 390 PeAF). Pooled single-procedure freedom from AF was 37.8% [95% confidence
interval 5.6-86.3%] at a mean follow-up period of 13.8 +/- 1.8 months for PAF and
59.2% (95% CI 41.4-74.9%) at a mean follow-up period of 12.9 +/- 6 months for
PeAF. There was a marked heterogeneity between studies (I2 = 93.8% for PAF and
88.3% for PeAF). The mean complication rate of rotor ablation among the reported
studies was 3.4%. Conclusion: The wide variability in success rate between
different centres performing rotor ablations suggests that the optimal ablation
strategy, particularly targeting rotors, is unclear. Results from randomized
studies are necessary before this technique can be considered as an established
clinical tool.
PMID- 29340596
TI - Commentary on: Effect of Botulinum Toxin A on Muscle Healing and its Implications
in Aesthetic and Reconstructive Surgery.
PMID- 29340597
TI - Managing dose-, damage- and data-rates in multi-frame spectrum-imaging.
AB - As an instrument, the scanning transmission electron microscope is unique in
being able to simultaneously explore both local structural and chemical
variations in materials at the atomic scale. This is made possible as both types
of data are acquired serially, originating simultaneously from sample
interactions with a sharply focused electron probe. Unfortunately, such scanned
data can be distorted by environmental factors, though recently fast-scanned
multi-frame imaging approaches have been shown to mitigate these effects. Here,
we demonstrate the same approach but optimized for spectroscopic data; we offer
some perspectives on the new potential of multi-frame spectrum-imaging (MFSI) and
show how dose-sharing approaches can reduce sample damage, improve
crystallographic fidelity, increase data signal-to-noise, or maximize usable
field of view. Further, we discuss the potential issue of excessive data-rates in
MFSI, and demonstrate a file-compression approach to significantly reduce data
storage and transmission burdens.
PMID- 29340598
TI - The Risk of Skin Necrosis Following Hyaluronic Acid Filler Injection in Patients
with a History of Cosmetic Rhinoplasty.
AB - Background: As the number of patients using dermal filler for face augmentation
increases, the number of adverse events associated with injection may increase.
Unpredictable repositioning of blood vessels and a more tenuous blood supply in
the operated nose may increase the risk of ischemia, necrosis and vascular
embolism following the filler injection. Objectives: To highlight the importance
of the patient's history of previous cosmetic procedures including rhinoplasty in
the emergence of vascular complications. Methods: Our medical records over a two
year period were reviewed retrospectively to identify all patients who were
treated at our center for vascular complications associated with facial
hyaluronic acid filler injections. In each case, the subject's demographic data
(gender and age), habitual status, past medical and surgical history, the
symptoms and clinical presentation at the first visit, the time interval between
the injection and the onset of symptoms, injected filler material and brand,
injection sites, the introduced treatment, and photographs were reviewed
carefully. Results: A total of seven patients were identified, each developing
skin necrosis following injection of the hyaluronic acid filler. All patients
reported a cosmetic rhinoplasty more than three years ago. Conclusions: Our
finding confirms the conjecture previously made in the literature and suggests
that the distinctive vascularity of the nose and the surrounding area may cause
filler augmentation induced vascular complications in patients whose vascular
circulation has already been compromised by a previous nose surgery.
PMID- 29340599
TI - A benchmark study of scoring methods for non-coding mutations.
AB - Motivation: Detailed knowledge of coding sequences has led to different candidate
models for pathogenic variant prioritization. Several deleteriousness scores have
been proposed for the non-coding part of the genome, but no large-scale
comparison has been realized to date to assess their performance. Results: We
compared the leading scoring tools (CADD, FATHMM-MKL, Funseq2 and GWAVA) and some
recent competitors (DANN, SNP and SOM scores) for their ability to discriminate
assumed pathogenic variants from assumed benign variants (using the ClinVar,
COSMIC and 1000 genomes project databases). Using the ClinVar benchmark, CADD was
the best tool for detecting the pathogenic variants that are mainly located in
protein coding gene regions. Using the COSMIC benchmark, FATHMM-MKL, GWAVA and
SOMliver outperformed the other tools for pathogenic variants that are typically
located in lincRNAs, pseudogenes and other parts of the non-coding genome.
However, all tools had low precision, which could potentially be improved by
future non-coding genome feature discoveries. These results may have been
influenced by the presence of potential benign variants in the COSMIC database.
The development of a gold standard as consistent as ClinVar for these regions
will be necessary to confirm our tool ranking. Availability and implementation:
The Snakemake, C++ and R codes are freely available from
https://github.com/Oncostat/BenchmarkNCVTools and supported on Linux. Contact:
damien.drubay@gustaveroussy.fr or stefan.michiels@gustaveroussy.fr. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 29340600
TI - Development and impact of a massive open online course (MOOC) for antimicrobial
stewardship.
AB - Background: The University of Dundee and the BSAC developed a massive open online
course (MOOC) to address the global need for education to support antimicrobial
stewardship in low- and middle-income countries. Methods: An interactive course,
Antimicrobial Stewardship: Managing Antibiotic Resistance, was developed and
delivered via the FutureLearn(c) platform. The course ran over four 6 week
periods during 2015 and 2016 supported by educators and was evaluated via data on
uptake and feedback from learners on impact on clinical practice. Results: In
total, 32 944 people, 70% of them healthcare professionals, from 163 countries
joined the course from Europe (49%), Asia (16%), Africa (13%), North America
(9%), Australia (8%) and South America (5%). Between 33% and 37% of joiners in
each run completed at least one step in any week of the course and 219
participants responded to a post-course survey. The course was rated good or
excellent by 208 (95%) of the participants, and 83 (38%) intended to implement
stewardship interventions in their own setting. A follow-up survey 6 months later
suggested that 49% had implemented such interventions. Conclusions: The MOOC has
addressed a global learning need by providing education free at the point of
access, and learning from its development will help others embarking upon similar
educational solutions. Initial quantitative and qualitative feedback suggests it
has engaged participants and complements traditional educational methods.
Measuring its real impact on clinical practice remains a challenge. The
FutureLearn(c) platform offers flexibility for MOOCs to be sustainable through
modification to remove educator facilitation but maintain active participant
discussion.
PMID- 29340601
TI - How to treat borderline resectable pancreatic cancer: current challenges and
future directions.
AB - Borderline resectable pancreatic cancer (BRPC) is an advanced tumor in contact
with the surrounding major vessels, making R0 resection difficult to achieve.
Neoadjuvant treatment is expected to provide substantial local control and
prolong survival. However, there is no standard treatment. I therefore conducted
a strategic literature search from January 2013 to September 2017 and identified
37 clinical studies of pancreatic cancer, including BRPC, to evaluate treatment
interventions. Twenty (54%) studies were prospective. Neoadjuvant regimens were
as follows: chemotherapy (CT) followed by chemoradiotherapy (CRT) or radiotherapy
(RT) (n = 16, 43%), CT alone (n = 11, 30%), CRT alone (n = 9, 24%) and RT alone
(n = 1, 3%). Radiotherapy was employed in 70% of the studies. Phase II studies
were most frequent (55%), and we were unable to identify a Phase III study. The
National Comprehensive Cancer Network's classifications were most frequently used
as criteria for BRPC, although resectability status is not standardized.
Radiological central review was used in three of eight multi-institutional
studies. Assessing on-going or planned clinical trials for BRPC, administration
of oxaliplatin, irinotecan, fluorouracil and leucovorin therapy or albumin-bound
paclitaxel plus gemcitabine therapy, and randomized trials that evaluate the
significance of CRT or RT combined with CT were identified as important topics
for further consideration. Although standardization of classifications and
improvement of infrastructure are required, a standard treatment of BRPC will
likely be developed, which will improve prognosis in the near future because
several important randomized trials are running.
PMID- 29340602
TI - Emergence of blaCTX-M-55 associated with fosA, rmtB and mcr gene variants in
Escherichia coli from various animal species in France.
AB - Objectives: In Asian countries, blaCTX-M-55 is the second most common ESBL
encoding gene. blaCTX-M-55 frequently co-localizes with fosA and rmtB genes on
epidemic plasmids, which remain sporadic outside Asia. During 2010-13, we
investigated CTX-M-55-producing Escherichia coli isolates and their co-resistance
to fosfomycin, aminoglycosides, fluoroquinolones and colistin as part of a global
survey of ESBLs in animals in France. Methods: blaCTX-M-55, fosA, rmtB and
plasmidic quinolone and colistin resistance genes were characterized by PCR,
sequencing and hybridization experiments. Plasmids were classified according to
their incompatibility groups and subtypes. Genotyping was performed by MLST and
repetitive extragenic palindromic sequence-based PCR. Results: Twenty-one E. coli
isolates from bovines (n = 16), dogs (n = 2), horses (n = 2) and a monkey
harboured blaCTX-M-55, were MDR and belonged to ST744 (n = 9) and 10 other
clones. blaCTX-M-55 was mostly located on IncF (n = 19), but also on IncI1 (n =
2) plasmids. On IncF33:A1:B1 plasmids, blaCTX-M-55 co-localized with the rmtB and
aac(6')-Ib genes and in one isolate with the fosA3 allele. Ten IncF46:A-:B20
plasmids, which were found in different clones from unrelated animals, also
carried the mcr-3 gene. blaCTX-M-55-carrying IncF18:A-:B1 plasmids were found in
different animal species from distinct locations and periods, and one
additionally carried the fosA4 gene. One isolate harboured the mcr-1 gene, which
did not co-localize with blaCTX-M-55. Conclusions: A large diversity of E. coli
clones and plasmid types supported the spread of blaCTX-M-55, together with
atypical resistance genes, in various animal species in France. fosA and rmtB
genes are emerging among animals in Europe and this issue is of concern for
public health.
PMID- 29340594
TI - Keratan sulfate, a complex glycosaminoglycan with unique functional capability.
AB - From an evolutionary perspective keratan sulfate (KS) is the newest
glycosaminoglycan (GAG) but the least understood. KS is a sophisticated molecule
with a diverse structure, and unique functional roles continue to be uncovered
for this GAG. The cornea is the richest tissue source of KS in the human body but
the central and peripheral nervous systems also contain significant levels of KS
and a diverse range of KS-proteoglycans with essential functional roles. KS also
displays important cell regulatory properties in epithelial and mesenchymal
tissues and in bone and in tumor development of diagnostic and prognostic
utility. Corneal KS-I displays variable degrees of sulfation along the KS chain
ranging from non-sulfated polylactosamine, mono-sulfated and disulfated
disaccharide regions. Skeletal KS-II is almost completely sulfated consisting of
disulfated disaccharides interrupted by occasional mono-sulfated N
acetyllactosamine residues. KS-III also contains highly sulfated KS disaccharides
but differs from KS-I and KS-II through 2-O-mannose linkage to serine or
threonine core protein residues on proteoglycans such as phosphacan and abakan in
brain tissue. Historically, the major emphasis on the biology of KS has focused
on its sulfated regions for good reason. The sulfation motifs on KS convey
important molecular recognition information and direct cell behavior through a
number of interactive proteins. Emerging evidence also suggest functional roles
for the poly-N-acetyllactosamine regions of KS requiring further investigation.
Thus further research is warranted to better understand the complexities of KS.
PMID- 29340603
TI - Characterization of Antibiosis to Diabrotica speciosa (Coleoptera: Chrysomelidae)
in Brazilian Maize Landraces.
AB - Resistance to insect pests can be found in several native, landrace plants and
can be an important alternative to conventional control methods. Diabrotica
speciosa (Germar) (Coleoptera: Chrysomelidae) larvae are important maize (Zea
mays L.) (Cyperales: Poaceae) root pests and finding native resistance in
landraces would greatly contribute to maize-breeding programs aimed at
controlling this pest. This study investigated whether the growth, survival,
oviposition rhythm, fecundity, and fertility of D. speciosa are negatively
influenced by specific maize landraces, and the existence of any morphological
barriers in the roots that may correlate with plant resistance to the larval
attack. Nineteen genotypes (17 landraces and 2 cultivars) were screened for
antibiosis in assays that were conducted in the laboratory using seedling maize
plants where the development time, longevity, weight, total survival, and sex
ratio of adults were evaluated. Out of nineteen genotypes, eight were selected
according to their resistance levels for an additional rearing study evaluating
oviposition and fecundity. Landrace Perola and cultivar SCS 154-Fortuna were
classified as resistant because they increased the maturation period from larva
to adult and decreased survivorship; and the landrace Palha Roxa was also
classified as resistant for showing a lower fertility rate than other landraces.
Resistant landraces that were infested by D. speciosa larvae showed greater
amounts of some morphological barriers comparing with uninfested plants. The
landraces classified as resistant may be considered in future plant-breeding
programs, aiming to develop resistant maize cultivars to D. speciosa larval
attack.
PMID- 29340605
TI - We can do better: a fresh look at echinocandin dosing.
PMID- 29340604
TI - Transient recruitment of M-Ras GTPase to phagocytic cups in RAW264 macrophages
during FcgammaR-mediated phagocytosis.
AB - M-Ras, a member of the Ras superfamily, is known to be involved in diverse
cellular processes. However, its involvement in FcgammaR-mediated phagocytosis
remains unknown. We examined the spatiotemporal localization of M-Ras during the
engulfment of IgG-opsonized erythrocytes (IgG-Es) in RAW264 macrophages. By the
live-cell imaging of fluorescent protein-fused M-Ras, we found that M-Ras was
localized to the membrane of phagocytic cups during the early stage of phagosome
formation. Notably, ratiometric image analysis revealed that M-Ras was
concentrated in the membrane of forming phagosomes. Moreover, our analysis of M
Ras mutant expression showed that phagosome formation was significantly inhibited
in cells expressing GDP-locked mutant M-Ras-S27N. In contrast, the expression of
wild-type M-Ras or GTP-locked mutant M-Ras-G22V facilitated the uptake of IgG-Es.
These data suggest that M-Ras is a novel component of the FcgammaR-mediated
phagocytic pathway and may regulate phagosome formation in macrophages.
PMID- 29340606
TI - Leaves, not roots or floral tissue, are the main site of rapid, external pressure
induced ABA biosynthesis in angiosperms.
AB - Rapid biosynthesis of abscisic acid (ABA) in the leaf, triggered by a decrease in
cell volume, is essential for a functional stomatal response. However, it is not
known whether rapid biosynthesis of ABA is also triggered in other plant tissues.
Through the application of external pressure to flower, root, and leaf tissues,
we test whether a reduction in cell volume can trigger rapid increases in ABA
levels across the plant body in two species, Solanum lycopersicum and Passiflora
tarminiana. Our results show that, in contrast to rapid ABA synthesis in the
leaf, flower and root tissue did not show a significant, increase in ABA level in
response to a drop in cell volume over a short time frame, suggesting that rapid
ABA biosynthesis occurs only in leaf, not in flower or root tissues. A gene
encoding the key, rate-limiting carotenoid cleavage enzyme (9-cis-epoxycarotenoid
dioxygenase, NCED) in the ABA biosynthetic pathway in S. lycopersicum, NCED1, was
upregulated to a lesser degree in flowers and roots compared with leaves in
response to applied pressure. In both species, floral tissues contained
substantially lower levels of the NCED substrate 9'-cis-neoxanthin than leaves,
and this ABA precursor could not be detected in roots. Slow and minimal ABA
biosynthesis was detected after 2 h in petals, indicating that floral tissue is
capable of synthesizing ABA in response to sustained water deficit. Our results
indicate that rapid ABA biosynthesis predominantly occurs in the leaves, and not
in other tissues.
PMID- 29340607
TI - Collection efficiency and acceptance maps of electron detectors for understanding
signal detection on modern scanning electron microscopy.
AB - Collection efficiency and acceptance maps of typical detectors in modern scanning
electron microscopes (SEMs) were investigated. Secondary and backscattered
electron trajectories from a specimen to through-the-lens and under-the-lens
detectors placed on an electron optical axis and an Everhart-Thornley detector
mounted on a specimen chamber were simulated three-dimensionally. The acceptance
maps were drawn as the relationship between the energy and angle of collected
electrons under different working distances. The collection efficiency
considering the detector sensitivity was also estimated for the various working
distances. These data indicated that the acceptance maps and collection
efficiency are keys to understand the detection mechanism and image contrast for
each detector in the modern SEMs. Furthermore, the working distance is the
dominant parameter because electron trajectories are drastically changed with the
working distance.
PMID- 29340608
TI - Could Increasing Cancer Incidence Be Tied to Human Adaptation of Living in
Extreme Environments?
PMID- 29340609
TI - Impact of antibiotic stewardship programmes in Asia: a systematic review and meta
analysis.
AB - Background: The use of antibiotic stewardship programmes (ASPs) is increasing in
Asia, but their effectiveness in reducing antibiotic consumption and their impact
on clinical outcomes is not known. Objectives: To determine the impact of ASPs
conducted in Asia on the consumption of antibiotics and on patients' clinical
outcomes. Methods: We systematically searched the Embase and Medline (PubMed)
databases for studies that compared antibiotic consumption or clinical outcomes
of patients in an Asian hospital or clinic with an ASP (intervention) with those
in a similar setting without an ASP (control). Meta-analyses of all-cause
mortality and hospital-acquired infection (HAI) were performed using random
effects models. Results: The search identified 77 studies of which 22 and 19
reported antibiotic usage and cost, respectively. Among these, 20 (91%) studies
reported reduced antibiotic usage and 19 (100%) reported cost savings in the
intervention group. Duration of antibiotic therapy was reduced in six of seven
studies in association with an ASP. Rates of all-cause mortality and HAI were not
significantly different between the intervention and control groups. However,
mortality rates were significantly improved by ASPs using drug monitoring, while
HAI rates were also improved by ASPs that included infection control or hand
hygiene programmes. Conclusions: In Asia, ASPs reduce antibiotic consumption in
hospital and clinic settings and do not worsen clinical outcomes. The findings
strongly support the broad implementation of antimicrobial stewardship
interventions in hospital and clinic settings in Asia.
PMID- 29340610
TI - Preclinical [18F]tetrafluoroborate-PET/CT imaging of pituitary gland hyperplasia.
PMID- 29340611
TI - Treatment of Nasal Deviation With Underlying Bony Asymmetry Secondary to
Augmentation Rhinoplasty in Asian Patients.
AB - Background: In Asian patients, nasal deviation secondary to augmentation
rhinoplasty may result from underlying bony asymmetry that was not corrected
intraoperatively. Diagnosis and treatment of this condition are complicated by
the masking effect of dorsal implants. Objectives: The authors applied computed
tomography (CT) to examine the causes of nasal deviation after augmentation
rhinoplasty. CT results were utilized in preoperative planning for revisional
surgery. Methods: Fifteen women with nasal deviation after augmentation
rhinoplasty and CT-confirmed bony asymmetry were included in a retrospective
study. To correct nasal deviation, the authors performed revisional rhinoplasty
with paramedian osteotomy and unilateral placement of extended spreader grafts at
the concave side of the keystone region. For patients with concomitant glabella
radix deviation, implants comprising expanded polytetrafluoroethylene or
autologous fascia were placed. Results: Of the 15 patients with nasal bony
asymmetry, 14 had developmental keystone asymmetry, and 1 had osteotomy-induced
keystone deviation. Six patients had developmental glabella asymmetry. Patients
received follow-up for an average of 11.2 months (range, 6-24 months). Revisional
procedures were considered successful in 13 patients; 2 patients required
additional surgery to address residual nasal deviation. Conclusions: CT is
valuable for the diagnosis of post-augmentation nasal deviation owing to
underlying bony asymmetry. Paramedian osteotomy with extended spreader grafting
at the concave side of the keystone area and correction of the glabella-radix
deviation are effective procedures to reposition the nasal axis along the midline
of the face.
PMID- 29340612
TI - Rice Field Spiders in China: A Review of the Literature.
AB - Many laboratory and field studies have been conducted on rice field spiders in
China. There are 375 species, 108 genera, and 22 families of rice field spiders
distributed within the major rice growing areas and 17 dominant species. The
biological and ecological characteristics of 17 rice field spider species have
been reported in detail. The biology and ecology of these species show
significant differences among regions, farmland habitats, and agricultural
practices. Future research should focus on rice field habitat diversity,
enhancing the insecticide resistance of dominant spider populations, implementing
large-scale breeding of spiders and augmentative release, breeding more leaf
dominant species, conducting biosafety assessment of spiders in transgenic crops.
PMID- 29340613
TI - Biomass increase under zinc deficiency caused by delay of early flowering in
Arabidopsis.
AB - Plants generally produce more biomass when all nutrients are available in
sufficient amounts. In addition to environmental constraints, genetic and
developmental factors, such as the transition from vegetative to reproductive
growth, restrict maximal biomass yield. Here, we report the peculiar observation
that a subset of Arabidopsis thaliana accessions produced larger shoot rosette
diameters when grown in zinc (Zn)-deficient conditions, compared with Zn
sufficient conditions. This was associated with early flowering that restricted
the leaf length under Zn sufficiency. Zinc deficiency repressed the expression of
FLOWERING LOCUS T (FT), which encodes a major regulator of flowering. Repression
or loss of FT increased the rosette diameter via a delay of the transition to
flowering, a longer phase of leaf growth, and an increased leaf number. The
transition to flowering reduced, but did not terminate, the proliferation of
established leaves. The size of individual leaf mesophyll cells was not affected
by Zn deficiency or by loss of FT, indicating that the larger rosette diameter
was caused by maintained proliferation of vegetative tissue. As a consequence,
early-flowering accessions under Zn deficiency grew to have larger rosette
diameters due to a delay of flowering, which explains the unusual increase of
vegetative biomass under nutrient deficiency.
PMID- 29340614
TI - Association of Polygenic Risk Score With Cognitive Decline and Motor Progression
in Parkinson Disease.
AB - Importance: Genetic factors have a well-known influence on Parkinson disease (PD)
susceptibility. The largest genome-wide association study (GWAS) identified 26
independent single-nucleotide polymorphisms (SNPs) associated with PD risk. Among
patients, the course and severity of symptom progression is variable, and little
is known about the potential association of genetic factors with phenotypic
variance. Objective: To assess whether GWAS-identified PD risk SNPs also have a
cumulative association with the progression of cognitive and motor symptoms in
patients with PD. Design, Setting, and Participants: This longitudinal population
based cohort study of 285 patients of European ancestry with incident PD
genotyped 23 GWAS SNPs. One hundred ninety-nine patients were followed up for a
mean (SD) of 5.3 (2.1) years for progression (baseline: June 1, 2001, through
November 31, 2007; follow-up: June 1, 2007, through August 31, 2013, with
mortality surveillance through December 31, 2016); 57 patients had died or were
too ill for follow-up, and 29 withdrew or could not be contacted. Movement
disorder specialists repeatedly assessed PD symptom progression. Main Outcomes
Measures: The combined association of PD risk loci, after creating a weighted
polygenic risk score (PRS), with cognitive decline, motor progression, and
survival, relying on Cox proportional hazards regression models and inverse
probability weights to account for censoring. Results: Of the 285 patients
undergoing genotyping, 160 were men (56.1%) and 125 were women (43.9%); the mean
(SD) age at diagnosis was 69.1 (10.4) years. The weighted PRS was associated with
significantly faster cognitive decline, measured by change in the Mini-Mental
State Examination (hazard ratio [HR] per 1 SD, 1.44; 95% CI, 1.00-2.07). The PRS
was also associated with faster motor decline, measured by time to Hoehn & Yahr
Scale stage 3 (HR, 1.34; 95% CI, 1.00-1.79) and change in Unified Parkinson's
Disease Rating Scale part III score (HR, 1.42; 95% CI, 1.00-2.01). Conclusions
and Relevance: Susceptibility SNPs for PD combined with a cumulative PRS were
associated with faster motor and cognitive decline in patients. Thus, these
genetic markers may be associated with not only PD susceptibility but also
disease progression in multiple domains.
PMID- 29340615
TI - A simple method to detect the tandem repeat of the cyp51A promoter in azole
resistant strains of Aspergillus fumigatus.
AB - We designed primers and cycling probes to detect the tandem repeat (TR) of cyp51A
promoter in Aspergillus fumigatus. A control-probe was designed to anneal to the
outside of the TR region, whereas a TR-probe was designed to anneal to the inside
of the TR region. For amplification and probe-hydrolysis detection, the
CycleavePCR system was used. Although the difference between Ct values of the
wild-type genome for the control-probe and the TR-probe was around -0.1, the
difference between Ct values of TR-harboring strains was around 0.7. These data
indicate that this is a simple method to detect TR in azole-resistant A.
fumigatus.
PMID- 29340616
TI - PyChimera: use UCSF Chimera modules in any Python 2.7 project.
AB - Motivation: UCSF Chimera is a powerful visualization tool remarkably present in
the computational chemistry and structural biology communities. Built on a C++
core wrapped under a Python 2.7 environment, one could expect to easily import
UCSF Chimera's arsenal of resources in custom scripts or software projects.
Nonetheless, this is not readily possible if the script is not executed within
UCSF Chimera due to the isolation of the platform. UCSF ChimeraX, successor to
the original Chimera, partially solves the problem but yet major upgrades need to
be undergone so that this updated version can offer all UCSF Chimera features.
Results: PyChimera has been developed to overcome these limitations and provide
access to the UCSF Chimera codebase from any Python 2.7 interpreter, including
interactive programming with tools like IPython and Jupyter Notebooks, making it
easier to use with additional third-party software. Availability and
implementation: PyChimera is LGPL-licensed and available at
https://github.com/insilichem/pychimera. Contact: jaime.rodriguezguerra@uab.cat
or jeandidier.marechal@uab.cat. Supplementary information: Supplementary data are
available at Bioinformatics online.
PMID- 29340617
TI - Facial Herpes Zoster Following Rhinoplasty: A Rare Complication.
PMID- 29340619
TI - Recurrent serious infections in patients with rheumatoid arthritis-results from
the British Society for Rheumatology Biologics Register.
AB - Objectives: To establish the rate of recurrent infection in RA patients recruited
to the British Society for Rheumatology Biologics Register - Rheumatoid
Arthritis. Secondary objectives were to establish whether the organ class of
index infection predicted future serious infection (SI). Methods: Using data from
the British Society for Rheumatology Biologics Register - Rheumatoid Arthritis, a
prospective observational cohort, we identified patients with at least one
episode of SI. Incidence rates of SI, recurrent SI within the same organ class as
the index infection and recurrent SI (of any class) were calculated. A Cox
proportional hazards model was used to identify predictors of SI. Results: In
total, 5289 subjects with at least one SI contributing 19 431 patient-years
follow-up were studied. The baseline annual rate of first SI was 4.6% (95% CI:
4.5, 4.7), increasing to 14.1% (95% CI: 13.5, 14.8) following an index infection.
Respiratory infections were the most frequent (44% of all events). Recurrent
infections mirrored the organ class of the index infection. Sepsis, increasing
age and polypharmacy were significant predictors of infection recurrence in a
fully adjusted model. The system class of index infection was associated with the
risk of a recurrent event; subjects who experienced sepsis had the highest risk
of subsequent SI within 12 months, 19.7% (95% CI: 15.1, 25.7). Conclusion:
Recurrent infections in RA are common. Understanding patterns and predictors of
recurrent infection together with the differential infection risk associated with
immunosuppressive agents will help personalize RA care, tailor treatment choices
better and mitigate against episodes of SI.
PMID- 29340618
TI - Mitochondrial Toxicity.
AB - Recent decades have seen a rapid increase in reported toxic effects of drugs and
pollutants on mitochondria. Researchers have also documented many genetic
differences leading to mitochondrial diseases, currently reported to affect ~1
person in 4,300, creating a large number of potential gene-environment
interactions in mitochondrial toxicity. We briefly review this history, and then
highlight cutting-edge areas of mitochondrial research including the role of
mitochondrial reactive oxygen species in signaling; increased understanding of
fundamental biological processes involved in mitochondrial homeostasis (DNA
maintenance and mutagenesis, mitochondrial stress response pathways, fusion and
fission, autophagy and biogenesis, and exocytosis); systemic effects resulting
from mitochondrial stresses in specific cell types; mitochondrial involvement in
immune function; the growing evidence of long-term effects of mitochondrial
toxicity; mitochondrial-epigenetic cross-talk; and newer approaches to test
chemicals for mitochondrial toxicity. We also discuss the potential importance of
hormetic effects of mitochondrial stressors. Finally, we comment on future areas
of research we consider critical for mitochondrial toxicology, including
increased integration of clinical, experimental laboratory, and epidemiological
(human and wildlife) studies; improved understanding of biomarkers in the human
population; and incorporation of other factors that affect mitochondria, such as
diet, exercise, age, and nonchemical stressors.
PMID- 29340620
TI - Delivery of Tapasin-modified CTL epitope peptide via cytoplasmic transduction
peptide induces CTLs by JAK/STAT signaling pathway in vivo.
AB - Hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) play a vital role
in viral control and clearance. Recent studies have elucidated that Tapasin, an
endoplasmic reticulum chaperone, is a well-known molecule that appears to be
essential in peptide-loading process. The Janus kinase/signal transducers and
activators of transcription (JAK/STAT) pathway plays an important role in immune
response regulation and cytokines secretion. We have previously verified that
fusion protein CTP-HBcAg18-27-Tapasin could facilitate the maturation of bone
marrow derived dendritic cells and enhance specific CTLs responses in vitro,
which might be associated with the activation of JAK/STAT signaling pathway. To
further explore whether JAK/STAT signaling pathway participated in specific
immune responses mediated by CTP-HBcAg18-27-Tapasin, we suppressed the JAK/STAT
pathway with pharmacological inhibitor (AG490) in vivo. Our studies showed that
the number of IFN-gamma+-CD8+ T cells was decreased significantly compared with
other groups after being blocked by AG490. The percentage of IFN-gamma+-CD4+ T
cells and IL-2-CD4+ T cells was also decreased. Moreover, lower expression levels
of Jak2, Tyk2, STAT1, and STAT4 were detected in AG490 group. In addition, the
secretion levels of Th1-like cytokines were decreased and a weaker specific T
cell response was observed in AG490 group. Furthermore, the levels of HBV DNA and
HBsAg in serum and expression levels of HBsAg and HBcAg in liver tissues were
elevated after this pathway was inhibited in HBV transgenic mice. These results
demonstrate that the JAK/STAT signaling pathway participates in Th1-oriented
immune response induced by CTP-HBcAg18-27-Tapasin and this might provide a
theoretical basis for HBV immunotherapy.
PMID- 29340621
TI - Examining Exposure Assessment in Shift Work Research: A Study on Depression Among
Nurses.
AB - Introduction: Coarse exposure assessment and assignment is a common issue facing
epidemiological studies of shift work. Such measures ignore a number of exposure
characteristics that may impact on health, increasing the likelihood of biased
effect estimates and masked exposure-response relationships. To demonstrate the
impacts of exposure assessment precision in shift work research, this study
investigated relationships between work schedule and depression in a large survey
of Canadian nurses. Methods: The Canadian 2005 National Survey of the Work and
Health of Nurses provided the analytic sample (n = 11450). Relationships between
work schedule and depression were assessed using logistic regression models with
high, moderate, and low-precision exposure groupings. The high-precision grouping
described shift timing and rotation frequency, the moderate-precision grouping
described shift timing, and the low-precision grouping described the
presence/absence of shift work. Final model estimates were adjusted for the
potential confounding effects of demographic and work variables, and bootstrap
weights were used to generate sampling variances that accounted for the survey
sample design. Results: The high-precision exposure grouping model showed the
strongest relationships between work schedule and depression, with increased odds
ratios [ORs] for rapidly rotating (OR = 1.51, 95% confidence interval [CI] = 0.91
2.51) and undefined rotating (OR = 1.67, 95% CI = 0.92-3.02) shift workers, and a
decreased OR for depression in slow rotating (OR = 0.79, 95% CI = 0.57-1.08)
shift workers. For the low- and moderate-precision exposure grouping models, weak
relationships were observed for all work schedule categories (OR range 0.95 to
0.99). Conclusions: Findings from this study support the need to consider and
collect the data required for precise and conceptually driven exposure assessment
and assignment in future studies of shift work and health. Further research into
the effects of shift rotation frequency on depression is also recommended.
PMID- 29340622
TI - Comment on: Cryofibrinogenaemia-a neglected disease.
PMID- 29340624
TI - Early and long-term outcomes of mitral valve repair for Barlow's disease: a
single-centre 16-year experience.
AB - OBJECTIVES: Following mitral valve repair for Barlow's disease, recurrent mitral
regurgitation (MR) is believed to occur frequently and is mainly attributed to
disease progression. METHODS: Between January 2000 and December 2015, 180
patients (40% women, mean age 58.7 +/- 13.5 years) with Barlow's disease
underwent mitral valve repair. To provide a longitudinal assessment of mitral
valve repair durability, a multistate model for interval-censored observations (4
states: 1, Grade 0/1+ MR; 2, Grade 2+ MR; 3, Grade 3+/4+ MR; 4,
reintervention/death) was developed. The mechanism of recurrent MR was assessed
echocardiographically. RESULTS: Early mortality was 1.7%. After hospital
discharge, 6 late reinterventions were performed. With death as a competing risk,
the 10-year overall reintervention-free survival and reintervention rates were
79.8% (95% confidence interval 72.7-87.6%) and 4.5% (95% confidence interval 2.0
10.2%), respectively. Echocardiographic follow-up was available for 165 (93%) of
hospital survivors with a total of 480 examinations. The incidence of both
recurrent Grade 2+ and Grade 3+/4+ MR was relatively low up to 10 years after
surgery. Grade 2+ MR did not always progress to higher regurgitation grade during
the follow-up period. Grade 3+/4+ regurgitation was highly associated with valve
related morbidity and mortality. Recurrent MR (>=Grade 2+) was predominantly
related to the technical aspects of valve repair. CONCLUSIONS: Despite the
complex valve abnormalities observed in patients with Barlow's disease, mitral
valve repair can be performed with good early and late outcomes and low rates of
recurrence of MR up to 10 years after surgery. Early and late valve repair
durability is good and remains stable over time, suggesting that underlying
disease progression has limited clinical significance.
PMID- 29340623
TI - Pharmacokinetics of rituximab and clinical outcomes in patients with anti
neutrophil cytoplasmic antibody associated vasculitis.
AB - Objectives: To study the determinants of the pharmacokinetics (PK) of rituximab
(RTX) in patients with ANCA-associated vasculitis (AAV) and its association with
clinical outcomes. Methods: This study included data from 89 patients from the
RTX in AAV trial who received the full dose of RTX (four weekly infusions of 375
mg/m2). RTX was quantified at weeks 2, 4, 8, 16 and 24, and summarized by
computing the trapezoidal area under the curve. We explored potential
determinants of the PK-RTX, and analysed its association with clinical outcomes:
achievement of remission at 6 months, duration of B-cell depletion and time to
relapse in patients who achieved complete remission. Results: RTX serum levels
were significantly lower in males and in newly diagnosed patients, and negatively
correlated with body surface area, baseline B-cell count and degree of disease
activity. In multivariate analyses, the main determinants of PK-RTX were sex and
new diagnosis. Patients reaching complete remission at month 6 had similar RTX
levels compared with patients who did not reach complete remission. Patients with
higher RTX levels generally experienced longer B-cell depletion than patients
with lower levels, but RTX levels at the different time points and area under the
curve were not associated with time to relapse. Conclusion: Despite the body
surface-area-based dosing protocol, PK-RTX is highly variable among patients with
AAV, its main determinants being sex and newly diagnosed disease. We did not
observe any relevant association between PK-RTX and clinical outcomes. The
monitoring of serum RTX levels does not seem clinically useful in AAV.
PMID- 29340625
TI - Seen through the patients' eyes: surgical safety and checklists.
AB - Objective: We sought to explore the views patients have towards surgical safety
and checklists. As a secondary aim, we explored if previous experience of error
or other patient characteristics influence these views. Design: A cross-sectional
survey study design was applied. Participants: The Flemish Patients' Platform
network and social media were used to recruit participants. Main outcome
measure(s): An 11-item questionnaire was designed to assess the following
constructs: perception of surgical safety, attitudes towards the WHO surgical
safety checklist and attitudes regarding checklist usage. Results: Respondents'
view (N = 444) on the risk of an adverse event showed considerable variation.
Respondents were positive towards the checklist, strongly agreeing that it would
impact positively on their safety. However, this positive perception did not
translate into an attitude where patients will actively inform themselves whether
a checklist is used. The majority of respondents have no difficulty with
repetitive verification of identity, procedure and location of the surgery.
Respondents with a clinical background were the least anxious. Views were divided
regarding hearing discussions around blood loss or airway problems. Conclusions:
Patients perceive the checklist as a reliable safety tool. They do not mind
repetitive verification of identity and procedure. However, hearing staff
discussing specific, explicit, risks could cause anxiousness in some patients.
Building a supportive and collaborative environment is needed to involve and
empower patients to contribute in the realization of a safe hospital environment.
PMID- 29340626
TI - Suppression of NLRP3 inflammasome by oral treatment with sulforaphane alleviates
acute gouty inflammation.
AB - Objective: The aetiology of gout is closely linked to the deposition of
monosodium uric acid (MSU) crystals and the consequent activation of the NOD-like
receptor family, pyrin domain containing 3 (NLRP3) inflammasome. In this study,
we investigated whether oral administration of an NLRP3 inhibitor would be
effective to attenuate the symptoms of gout. Methods: The effects of oral
administration with sulforaphane (SFN) were examined in two mouse models of acute
gout induced by injection of MSU crystals into footpads or air pouch. The
production of caspase-1 (p10) and IL-1beta was examined by immunoblotting and
ELISA as hallmarks of NLRP3 inflammasome activation. Results: Oral administration
of SFN attenuated MSU crystal-induced swelling and neutrophil recruitment in a
mouse foot acute gout model, correlating with the suppression of the NLRP3
inflammasome activation in foot tissues. Consistently, oral administration of SFN
blocked MSU-crystal-induced activation of the NLRP3 inflammasome in a mouse air
pouch gout model. SFN suppressed NLRP3 inflammasome activation induced by MSU
crystals, adenosine triphosphate and nigericin but not by poly(dA:dT) in primary
mouse macrophages, independent of the reactive oxygen species pathway. SFN
inhibited ligand-independent activation of the NLRP3 inflammasome, suggesting
that SFN may act directly on the NLRP3 inflammasome complex. Conclusion: Oral
administration of SFN effectively alleviated acute gouty inflammation by
suppression of the NLRP3 inflammasome. Our results provide a novel strategy in
which oral treatment with SFN may be beneficial in preventing acute attacks of
gout.
PMID- 29340627
TI - In search of a diagnostic test for polymyalgia rheumatica: is positron emission
tomography the answer?
PMID- 29340628
TI - The Importance of Umbilical Blood Supply and Umbilical Delay in Secondary
Abdominoplasty: A Case Report.
AB - The umbilicus is an important aesthetic landmark of the abdomen. It possesses a
dual blood supply that allows it to survive either on its stalk if the skin
surrounding the umbilicus is incised, or through the surrounding subdermal
circulation if the stalk is transected. This is an important concept to consider
in order to avoid umbilical ischemia and necrosis during abdominoplasty,
especially if there is any past surgical history suggesting alteration to its
blood supply. This case study depicts this importance and the importance of the
use of delay in order to improve perfusion to the umbilicus prior to secondary
abdominoplasty. In this case, a 47-year-old woman had undergone abdominoplasty
two years previously and requested further improvement of her abdominal contour.
At her original operation, the umbilical stalk was transected during hernia
repair and the umbilicus was "floated" inferiorly to its new position. Thus,
during her second revisionary abdominoplasty, it was crucial to consider the
adequacy of umbilical blood supply to minimize and avoid the possibility of
ischemic necrosis of the umbilicus due to alteration of umbilical blood supply.
Therefore, a delay procedure of the umbilicus was performed. This case report
emphasizes the need for proper consideration of umbilical blood supply, and delay
of the umbilicus if alterations to its normal blood supply are known to be
present or suspected to exist.
PMID- 29340629
TI - DEVELOPMENT OF A SET OF MESH-BASED AND AGE-DEPENDENT CHINESE PHANTOMS AND
APPLICATION FOR CT DOSE CALCULATIONS.
AB - Phantoms for organ dose calculations are essential in radiation protection
dosimetry. This article describes the development of a set of mesh-based and age
dependent phantoms for Chinese populations using reference data recommended by
the Chinese government and by the International Atomic Energy Agency (IAEA).
Existing mesh-based RPI adult male (RPI-AM) and RPI adult female (RPI-AF)
phantoms were deformed to form new phantoms according to anatomical data for the
height and weight of Chinese individuals of 5 years old male, 5 years old female,
10 years old male, 10 years old female,15 years old male, 15 years old female,
adult male and adult female-named USTC-5 M, USTC-5F, USTC-10M, USTC-10F, USTC
15M, USTC-15F, USTC-AM and USTC-AF, respectively. Following procedures to ensure
the accuracy, more than 120 organs/tissues in each model were adjusted to match
the Chinese reference parameters and the mass errors were within 0.5%. To
demonstrate the usefulness, these new set of phantoms were combined with a fully
validated model of the GE LightSpeed Pro 16 multi-detector computed tomography
(MDCT) scanner and the GPU-based ARCHER Monte Carlo code to compute organ doses
from CT examinations. Organ doses for adult models were then compared with the
data of RPI-AM and RPI-AF under the same conditions. The absorbed doses and the
effective doses of RPI phantoms are found to be lower than these of the USTC
adult phantoms whose body sizes are smaller. Comparisons for the doses among
different ages and genders were also made. It was found that teenagers receive
more radiation doses than adults do. Such Chinese-specific phantoms are clearly
better suited in organ dose studies for the Chinese individuals than phantoms
designed for western populations. As already demonstrated, data derived from age
specific Chinese phantoms can help CT operators and designers to optimize image
quality and doses.
PMID- 29340630
TI - Sutureless prosthesis for failed small Mitroflow valves: the Perceval-after
Mitroflow procedure.
AB - Because of its favourable haemodynamic characteristics and easy implantability,
Mitroflow aortic valve bioprosthesis has been the valve of choice for many
surgeons in patients with small aortic annulus. Disappointingly, early structural
valve deterioration and high transvalvular gradients have been reported mostly in
older patients with small prostheses. Reimplanting a new stented prosthesis
sutured in a narrow and damaged annulus is technically challenging and demanding
mainly in high-risk patients. Valve-in-valve transcatheter aortic valve
implantation has been proposed as a viable option; however, it presents
significant limitations because of residual high transprosthetic pressure
gradients and risk of coronary occlusion. We report a series of 8 patients, with
medium-term follow-up, who underwent successful Perceval-S surgical sutureless
aortic implant after the removal of a degenerated small Mitroflow valve. No early
mortality occurred, but 1 patient died 4 months postoperatively due to
gastrointestinal disease. No major complications occurred. Early and mid-term
postoperative pressure gradients were low (mean gradients 13.1 +/- 3.3 mmHg and
10.2 +/- 3.8 mmHg, respectively). In operable patients with a degenerated
Mitroflow valve, these favourable clinical and haemodynamic results suggest that
the sutureless solution is a simple, valid and safer alternative to conventional
redo valve replacement or to valve-in-valve transcatheter aortic valve
implantation.
PMID- 29340631
TI - A better understanding of ambulance personnel's attitude towards real-time
resuscitation feedback.
AB - Objective: High-quality chest compressions during cardiopulmonary resuscitation
(CPR) play a significant role in surviving cardiac arrest. Chest-compression
quality can be measured and corrected by real-time CPR feedback devices, which
are not yet commonly used. This article looks at the acceptance of such systems
in comparison of equipped and unequipped personnel. Design: Two groups of
emergency medical services' (EMS) personnel were interviewed using standardized
questionnaires. Setting: The survey was conducted in the German cities Dortmund
and Munster. Participants: Overall, 205 persons participated in the survey: 103
paramedics and emergency physicians from the Dortmund fire service and 102
personnel from the Munster service. Intervention: The staff of the Dortmund
service were not equipped with real-time feedback systems. The test group of
equipped personnel of the ambulance service of Munster Fire brigade uses real
time feedback systems since 2007. Main outcome measure: What is the acceptance
level of real-time feedback systems? Are there differences between equipped and
unequipped personnel? Results: The total sample is receptive towards real-time
feedback systems. More than 80% deem the system useful. However, this study
revealed concerns and prejudices by unequipped personnel. Negative ratings are
significantly lower at the Munster site that is experienced with the use of the
real-time feedback system in contrast to the Dortmund site where no such
experience exists-the system's use in daily routine results in better evaluation
than the expectations of unequipped personnel. Conclusions: Real-time feedback
systems receive overall positive ratings. Prejudices and concerns seem to
decrease with continued use of the system.
PMID- 29340632
TI - Developing a set of indicators to monitor quality in ambulatory diabetes care
using a modified Delphi panel process.
AB - Objective: There is a large evidence to practice gap in diabetes care with
limited performance assessments that capture the full spectrum of care delivery.
Our study aimed to develop a set of ambulatory diabetes quality indicators across
six domains (effectiveness, safety, patient-centered, timely, equitable and
efficient) to provide a broad view of quality. Design: A modified Delphi panel
process was conducted. Phase I involved compiling a list of indicators through
literature review and generation of patient and healthcare provider-derived
indicators through interviews and surveys, respectively. Phase II involved
panelists rating indicators using the Agency for Healthcare Research and Quality
measure attributes on 9-point Likert scale, attending a face-to-face meeting
followed by re-rating, and final ranking. Setting: This study was conducted
across five adult academic medical centers affiliated with the University of
Toronto. Participants: A multi-disciplinary Delphi panel (n = 16) including
patients was assembled. Main Outcome measure: For indicator advancement for
ranking, >=75% of panelists' responses in the top tertile (between 7 and 9) with
a median composite score of >=7 was required. Results: There were 202 indicators
included in the Delphi panel process including 171 from a comprehensive
literature review, 14 from patient interviews, and 17 from healthcare provider
surveys. Following the first round, 40 indicators proceeded directly to ranking,
while 162 indicators were re-rated and distilled down to 12 for ranking. In the
final ranking round, the 52 indicators were reduced to 35 including 13 effective,
10 safe, 6 patient-centered, 1 equitable, 3 efficient and 2 timely indicators.
Conclusion: Thirty-five selected indicators developed with broad stakeholder
engagement can be used to monitor quality in diabetes care.
PMID- 29340633
TI - Kinking of an open stent graft after total arch replacement with the frozen
elephant technique for acute Type A aortic dissection.
AB - Recently, in Japan, the J Graft Open Stent Graft (JOSG) was commercialized for
surgical repair of an aortic aneurysm and aortic dissection and the frozen
elephant trunk technique was applied. Kinking of the JOSG is a rare adverse event
that requires additional intervention. We experienced 2 patients who developed
kinking of a JOSG after translocated total arch replacement with the frozen
elephant trunk technique for acute Type A aortic dissection. Both patients had
intermittent claudication with a decreased ankle-brachial pressure index after
the operation. Computed tomography angiography showed kinking between the non
stent and stent parts of the JOSG. Therefore, we performed endovascular repair. A
severely angulated arch preserved by a translocated technique may lead to kinking
of a JOSG. This suggests that the removed non-stent part should be as short as
possible to prevent kinking of the JOSG.
PMID- 29340634
TI - Efficient decellularization for bovine pericardium with extracellular matrix
preservation and good biocompatibility.
AB - OBJECTIVES: In this study, we sought to explore an efficient decellularization
protocol for bovine pericardia with better extracellular matrix preservation and
good biocompatibility. METHODS: Bovine pericardia were decellularized by sodium
dodecyl sulphate (SDS), SDS + sodium deoxycholate (SD), Triton X-100 (TX), TX +
SD (TS), freeze-thaw cycles + SDS + SD (FSS) and freeze-thaw cycles + TX + SD
(FTS), respectively. Untreated pericardia were used as native control.
Histological examination, residual cellular content analysis, biochemical and
biomechanical evaluations and cytotoxicity assay were performed to investigate
decellularization efficiency, xenoantigens removal, extracellular matrix
preservation and biocompatibility. In vivo biocompatibility was evaluated using a
subcutaneous implantation method in rats. RESULTS: Among these protocols, FSS and
FTS protocols were the most effective methods to remove both the DNA material and
the galactose-alpha-1,3-galactose antigen. TX, TS and FTS bovine pericardia
maintained the collagen content and had no cytotoxicity to human umbilical vein
endothelial cells. The contents of elastin and glycosaminoglycan were lost to
different degrees after decellularization, with the highest content of
preservation with TX, followed by TS and FTS. Consistently, no significant
difference was found between native bovine pericardia and TX, TS or FTS bovine
pericardia. In vivo, FTS implants had minimal infiltration of macrophages and T
lymphocytes, with no histological evidence of peri-implant necrosis and
calcification. CONCLUSIONS: These results suggested that the FTS protocol showed
optimal decellularization results with better extracellular matrix preservation
and good biocompatibility. It may be a suitable protocol for producing a suitable
scaffold for heart tissue engineering.
PMID- 29340635
TI - Nutrient digestibility response to sugarcane bagasse addition and corn particle
size in normal and high Na diets for broilers.
AB - Improving diet digestibility is important to the broiler industry. Therefore,
this study focused on optimizing the physical structure of feed ingredients and
addition of dietary fiber as strategies to improve nutrient digestibility in low
and high sodium diets. A total of 672 day-old Ross 308 male broilers was
allocated to 48 pens using a 2 * 2 * 2 factorial arrangement of treatments with 2
particle sizes of corn (coarse 3,576 MUm or fine 1,113 MUm geometric mean
diameter), 2 levels of sugarcane bagasse (SB) (0 or 2%), and 2 levels of Na (0.16
or 0.4%). Protein digestibility coefficient was measured using pooled distal
ileal digesta of 3 birds per pen on d 24. Meanwhile, starch and gross energy
digestibility coefficients were measured using pooled duodenal, distal jejunal,
and distal ileal digesta of 3 birds per pen on d 24. Coarsely ground corn (CC)
resulted in improved ileal protein digestibility (P < 0.05). Addition of 2% SB
increased starch digestibility in the duodenum (P < 0.05), distal jejunum (P <
0.001), and distal ileum (P < 0.001), and increased protein digestibility in
distal ileum (P < 0.01). A significant particle size * SB * Na interaction was
observed for ileal energy digestibility (P < 0.05). The SB increased ileal energy
digestibility only in birds fed the diet with finely ground corn (FC) and 0.16%
Na. These findings demonstrate that SB and CC are able to improve nutrient
digestibility. It can be recommended for the poultry industry to use SB and
coarsely ground corn in feed to improve the utilization of nutrients.
PMID- 29340636
TI - Changes in Socioeconomic Differences in Hospital Days With Age: Cumulative
Disadvantage, Age-as-Leveler, or Both?
AB - Objectives: Length of hospital stay is inversely associated with socioeconomic
status (SES). It is less clear whether socioeconomic disparities in numbers of
hospital days diverge or converge with age. Method: Longitudinal linked Finnish
registry data (1988-2007) from 137,653 men and women aged 50-79 years at the end
of 1987 were used. Trajectories of annual total hospital days by education,
household income, and occupational class were estimated using negative binomial
models. Results: Men and women with higher education, household income, and
occupational class had fewer hospital days in 1988 than those with lower SES.
Hospital days increased between 1988 and 2007. For some age groups, higher SES
was associated with a faster annual rate of increase, resulting in narrowing rate
ratios of hospital days between SES groups (relative differences); the rate
ratios remained stable for other groups. Absolute SES differences in numbers of
hospital days appeared to diverge with age among those aged 50-69 years at
baseline, but converge among those aged 70-79 years at baseline. Discussion: The
hypotheses that socioeconomic disparities in health diverge or converge with age
may not be mutually exclusive; we demonstrated convergence/maintenance in
relative differences for all age groups, but divergence or convergence in
absolute differences depending on age.
PMID- 29340637
TI - Cohort Profile: The Swedish Longitudinal Occupational Survey of Health (SLOSH).
PMID- 29340638
TI - Dietary energy, digestible lysine, and available phosphorus levels affect growth
performance, carcass traits, and amino acid digestibility of broilers.
AB - A 3-factor, 3-level Box-Behnken design was used to investigate the interaction
effect of dietary digestible lysine (dLys, 9.5, 10.5, 11.5 g/kg), apparent
metabolizable energy (AMEn, 12.77, 13.19, 13.61 MJ/kg) and available P (avP, 3.0,
4.0, 5.0 g/kg) levels on performance and amino acid (AA) digestibility of Ross
308 male broilers (n = 1,050) from d 14 to 34. The design consisted of 15
treatments each replicated 5 times with 12 birds per replicate. On d 34, 3 birds
were sampled from each pen to collect ileal digesta (pooled per pen) to analyze
AA. Response surface was fitted by first-, second-, or third-degree polynomial
regressions in JMP statistical software v. 12.0.1. Feed intake (FI), weight gain
(WG) and feed conversion ratio (FCR) were affected by dLys (linear and quadratic,
P < 0.01), AMEn (linear, P < 0.01) and AMEn * avP (P < 0.01). Increased dLys
increased FI but increased AMEn decreased FI in the birds fed the low-avP diet.
However, when the avP level in the diet was increased, FI decreased to 13 MJ/kg
AMEn and remained constant thereafter. Increased dLys increased WG whereas an
increase in AMEn decreased WG in the birds fed the low-avP diet but had no effect
on WG in those fed the high-avP diet. Increased dLys decreased FCR whereas
increased AMEn decreased FCR in the birds fed the low-avP diet but had no effect
on FCR in those fed the high-avP diet. Increased dLys increased breast yield
percentage (linear, P < 0.01 and quadratic, P < 0.05) whereas increased AMEn
decreased breast yield percentage (linear, P < 0.01). Dietary levels of dLys or
avP had positive, linear effects on apparent ileal digestibility (AID) of
methionine (P < 0.01) and threonine (P < 0.01) but had no effect on other AA (P >
0.05). These results indicate that increasing dLys levels above current industry
standard would improve broiler performance irrespective of AMEn or avP levels of
the diet.
PMID- 29340640
TI - In Vivo Three-Dimensional Lamina Cribrosa Strains in Healthy, Ocular
Hypertensive, and Glaucoma Eyes Following Acute Intraocular Pressure Elevation.
AB - Purpose: To compare in vivo lamina cribrosa (LC) strains (deformations) following
acute IOP elevation in healthy, glaucoma, and ocular hypertensive subjects.
Methods: There were 20 healthy, 20 high-tension primary open-angle glaucoma
(POAG), 16 primary angle-closure glaucoma (PACG), and 20 ocular hypertensive
(OHT; with normal visual fields) eyes studied. For each test eye, the optic nerve
head was imaged three times (at baseline IOP, following an acute elevation of IOP
to approximately 35 then 45 mm Hg using an ophthalmodynamomter) using optical
coherence tomography (OCT). A three-dimensional (3D) strain-mapping algorithm was
applied to both sets of baseline and IOP-elevated OCT volumes to extract IOP
induced 3D strains. Octant-wise LC strains were also extracted to study the
pattern of local deformation. Results: The average LC strain in OHT subjects
(3.96%) was significantly lower than that measured in healthy subjects (6.81%; P
< 0.05). On average, POAG subjects experienced higher strain than the PACG
subjects (4.05%), healthy subjects experienced higher strains than the POAG and
PACG subjects, but these difference were not statistically significant. Local LC
deformations showed lowest strain in the infero-temporal and temporal octant in
the POAG and OHT subjects. Conclusions: We demonstrate measurable LC strains in
vivo in humans as a response to acute IOP elevation. In this population, our data
suggest that OHT LCs experience lower IOP-induced strains than healthy LCs.
PMID- 29340639
TI - Biomechanical Rigidity and Quantitative Proteomics Analysis of Segmental Regions
of the Trabecular Meshwork at Physiologic and Elevated Pressures.
AB - Purpose: The extracellular matrix (ECM) of the trabecular meshwork (TM) modulates
resistance to aqueous humor outflow, thereby regulating IOP. Glaucoma, a leading
cause of irreversible blindness worldwide, is associated with changes in the ECM
of the TM. The elastic modulus of glaucomatous TM is larger than age-matched
normal TM; however, the biomechanical properties of segmental low (LF) and high
flow (HF) TM regions and their response to elevated pressure, are unknown.
Methods: We perfused human anterior segments at two pressures using an ex vivo
organ culture system. After extraction, we measured the elastic modulus of HF and
LF TM regions by atomic force microscopy and quantitated protein differences by
proteomics analyses. Results: The elastic modulus of LF regions was 2.3-fold
larger than HF regions at physiological (1*) pressure, and 7.4-fold or 3.5-fold
larger than HF regions at elevated (2*) pressure after 24 or 72 hours,
respectively. Using quantitative proteomics, comparisons were made between HF and
LF regions at 1* or 2* pressure. Significant ECM protein differences were
observed between LF and HF regions perfused at 2*, and between HF regions at 1*
compared to 2* pressures. Decorin, TGF-beta-induced protein, keratocan, lumican,
dermatopontin, and thrombospondin 4 were common differential candidates in both
comparisons. Conclusions: These data show changes in biomechanical properties of
segmental regions within the TM in response to elevated pressure, and levels of
specific ECM proteins. Further studies are needed to determine whether these ECM
proteins are specifically involved in outflow resistance and IOP homeostasis.
PMID- 29340641
TI - Effects of Age-Related Macular Degeneration on Driving Performance.
AB - Purpose: To explore differences in driving performance of older adults with age
related macular degeneration (AMD) and age-matched controls, and to identify the
visual determinants of driving performance in this population. Methods:
Participants included 33 older drivers with AMD (mean age [M] = 76.6 +/- 6.1
years; better eye Age-Related Eye Disease Study grades: early [61%] and
intermediate [39%]) and 50 age-matched controls (M = 74.6 +/- 5.0 years). Visual
tests included visual acuity, contrast sensitivity, visual fields, and motion
sensitivity. On-road driving performance was assessed in a dual-brake vehicle by
an occupational therapist (masked to drivers' visual status). Outcome measures
included driving safety ratings (scale of 1-10, where higher values represented
safer driving), types of driving behavior errors, locations at which errors were
made, and number of critical errors (CE) requiring an instructor intervention.
Results: Drivers with AMD were rated as less safe than controls (4.8 vs. 6.2; P =
0.012); safety ratings were associated with AMD severity (early: 5.5 versus
intermediate: 3.7), even after adjusting for age. Drivers with AMD had higher CE
rates than controls (1.42 vs. 0.36, respectively; rate ratio 3.05, 95% confidence
interval 1.47-6.36, P = 0.003) and exhibited more observation, lane keeping, and
gap selection errors and made more errors at traffic light-controlled
intersections (P < 0.05). Only motion sensitivity was significantly associated
with driving safety in the AMD drivers (P = 0.005). Conclusions: Drivers with
early and intermediate AMD can exhibit impairments in their driving performance,
particularly during complex driving situations; motion sensitivity was most
strongly associated with driving performance. These findings have important
implications for assessing the driving ability of older drivers with visual
impairment.
PMID- 29340642
TI - Identifying Corneal Infections in Formalin-Fixed Specimens Using Next Generation
Sequencing.
AB - Purpose: We test the ability of next-generation sequencing, combined with
computational analysis, to identify a range of organisms causing infectious
keratitis. Methods: This retrospective study evaluated 16 cases of infectious
keratitis and four control corneas in formalin-fixed tissues from the pathology
laboratory. Infectious cases also were analyzed in the microbiology laboratory
using culture, polymerase chain reaction, and direct staining. Classified
sequence reads were analyzed with two different metagenomics classification
engines, Kraken and Centrifuge, and visualized using the Pavian software tool.
Results: Sequencing generated 20 to 46 million reads per sample. On average, 96%
of the reads were classified as human, 0.3% corresponded to known vectors or
contaminant sequences, 1.7% represented microbial sequences, and 2.4% could not
be classified. The two computational strategies successfully identified the
fungal, bacterial, and amoebal pathogens in most patients, including all four
bacterial and mycobacterial cases, five of six fungal cases, three of three
Acanthamoeba cases, and one of three herpetic keratitis cases. In several cases,
additional potential pathogens also were identified. In one case with
cytomegalovirus identified by Kraken and Centrifuge, the virus was confirmed by
direct testing, while two where Staphylococcus aureus or cytomegalovirus were
identified by Centrifuge but not Kraken could not be confirmed. Confirmation was
not attempted for an additional three potential pathogens identified by Kraken
and 11 identified by Centrifuge. Conclusions: Next generation sequencing combined
with computational analysis can identify a wide range of pathogens in formalin
fixed corneal specimens, with potential applications in clinical diagnostics and
research.
PMID- 29340643
TI - Association of Low Luminance Questionnaire With Objective Functional Measures in
Early and Intermediate Age-Related Macular Degeneration.
AB - Purpose: To determine whether Low Luminance Questionnaire (LLQ) scores are
associated with objective measures of visual function in early and intermediate
age-related macular degeneration (AMD). Methods: Cross-sectional study of
subjects with early AMD Age-Related Eye Disease Study (AREDS) stage 2, N = 33),
intermediate AMD (AREDS stage 3, N = 47), and age-matched healthy controls (N =
21). Subjects were interviewed with the LLQ. Psychophysical tests performed
included best-corrected visual acuity (BCVA), mesopic microperimetry, dark
adaptometry (DA), low luminance visual acuity (LLVA), and cone contrast test
(CCT). Low luminance deficit (LLD) was the difference in the number of letters
read under photopic versus low luminance settings. The relationship between LLQ
and visual function test scores was assessed with linear regression. Results:
Subjects with intermediate AMD had significantly lower LLQ composite scores (mean
= 75.8 +/- 16.7; median = 76, range [29, 97]) compared with early AMD (mean =
85.3 +/- 13.3; median = 88, range [50, 100], P = 0.007) or controls (mean = 91.4
+/- 6.5; median = 94, range [79, 99], P < 0.001) in the overall cohort. LLQ
composite scores were associated with computerized BCVA (beta = 0.516),
computerized LLVA at two background luminance (1.3 cd/m2, beta = 0.660; 0.5
cd/m2, beta = 0.489) along with their respective computerized LLDs (beta = -0.531
and -0.467), rod intercept (beta = -0.312), and CCT green (beta = 0.183) (all P <
0.05). Only the computerized LLVAs and computerized LLDs remained statistically
significant after adjusting for AMD versus control status (P < 0.05). Among AMD
subjects, LLQ composite scores were significantly associated with the
computerized LLVAs (beta = 0.622 and 0.441) and LLDs (beta = -0.795 and -0.477)
at both the 1.3 and 0.5 cd/m2 luminance levels, respectively, and these
associations remained significant after adjusting for AMD severity (P < 0.05).
Conclusions: Among subjects with early and intermediate AMD, LLQ scores were
significantly associated with computerized LLVA and LLD. LLQ is a useful patient
centered functional measure of visual impairment in early and intermediate AMD.
PMID- 29340645
TI - A Plasma Metabolomic Signature Involving Purine Metabolism in Human Optic Atrophy
1 (OPA1)-Related Disorders.
AB - Purpose: Dominant optic atrophy (DOA; MIM [Mendelian Inheritance in Man] 165500),
resulting in retinal ganglion cell degeneration, is mainly caused by mutations in
the optic atrophy 1 (OPA1) gene, which encodes a dynamin guanosine triphosphate
(GTP)ase involved in mitochondrial membrane processing. This work aimed at
determining whether plasma from OPA1 pathogenic variant carriers displays a
specific metabolic signature. Methods: We applied a nontargeted clinical
metabolomics pipeline based on ultra-high-pressure liquid chromatography coupled
to high-resolution mass spectrometry (UHPLC-HRMS) allowing the exploration of 500
polar metabolites in plasma. We compared the plasma metabolic profiles of 25
patients with various OPA1 pathogenic variants and phenotypes to those of 20
healthy controls. Statistical analyses were performed using univariate and
multivariate (principal component analysis [PCA], orthogonal partial least
squares discriminant analysis [OPLS-DA]) methods and a machine learning approach,
the Biosigner algorithm. Results: A robust and relevant predictive model
characterizing OPA1 individuals was obtained, based on a complex panel of
metabolites with altered concentrations. An impairment of the purine metabolism,
including significant differences in xanthine, hypoxanthine, and inosine
concentrations, was at the foreground of this signature. In addition, the
signature was characterized by differences in urocanate, choline, phosphocholine,
glycerate, 1-oleoyl-rac-glycerol, rac-glycerol-1-myristate, aspartate, glutamate,
and cystine concentrations. Conclusions: This first metabolic signature reported
in the plasma of patient carrying OPA1 pathogenic variants highlights the
unexpected involvement of purine metabolism in the pathophysiology of DOA.
PMID- 29340646
TI - Visual Fixation Instability in Multiple Sclerosis Measured Using SLO-OCT.
AB - Purpose: Precise measurements of visual fixation and its instability were
recorded during optical coherence tomography (OCT) as a marker of neural network
dysfunction in multiple sclerosis (MS), which could be used to monitor disease
progression or response to treatment. Methods: A total of 16 MS patients and 26
normal subjects underwent 30 seconds of scanning laser ophthalmoscope (SLO)-based
eye tracking during OCT scanning of retinal layer thickness. Study groups
consisted of normal eyes, MS eyes without prior optic neuritis (MS wo ON), and MS
eyes with prior optic neuritis (MS + ON). Kernel density estimation quantified
fixation instability from the distribution of fixation points on the retina. In
MS wo ON eyes, fixation instability was compared to other measures of visual and
neurologic function. Results: Fixation instability was increased in MS wo ON eyes
(0.062 deg2) compared to normal eyes (0.030 deg2, P = 0.015). A further increase
was seen for MS + ON eyes (0.11 deg2) compared to MS wo ON (P = 0.04) and normal
(P = 0.006) eyes. Fixation instability correlated weakly with ganglion cell layer
(GCL) volume and showed no correlation with low-contrast letter acuity, EDSS
score, or SDMT score. Conclusions: Fixation instability reflects the integrity of
a widespread neural network germane to visual processing and ocular motor
control, and is disturbed in MS. Further study of visual fixation, including the
contribution of microsaccades to fixation instability, may provide insight into
the localization of fixation abnormalities in MS and introduce innovative and
easily measured outcomes for monitoring progression and treatment response.
PMID- 29340644
TI - Proteasome Inhibition Increases the Efficiency of Lentiviral Vector-Mediated
Transduction of Trabecular Meshwork.
AB - Purpose: To determine if proteasome inhibition using MG132 increased the
efficiency of FIV vector-mediated transduction in human trabecular meshwork (TM)
1 cells and monkey organ-cultured anterior segments (MOCAS). Methods: TM-1 cells
were pretreated for 1 hour with 0.5% dimethyl sulfoxide (DMSO; vehicle control)
or 5 to 50 MUM MG132 and transduced with FIV.GFP (green fluorescent protein)- or
FIV.mCherry-expressing vector at a multiplicity of transduction (MOT) of 20. At
24 hours, cells were fixed and stained with antibodies for GFP, and positive
cells were counted, manually or by fluorescence-activated cell sorting (FACS).
Cells transduced with FIV.GFP particles alone were used as controls. The effect
of 20 MUM MG132 treatment on high- and low-dose (2 * 107 and 0.8 * 107
transducing units [TU], respectively) FIV.GFP transduction with or without MG132
was also evaluated in MOCAS using fluorescence microscopy. Vector genome
equivalents in cells and tissues were quantified by quantitative (q)PCR on DNA.
Results: In the MG132 treatment groups, there was a significant dose-dependent
increase in the percentage of transduced cells at all concentrations tested.
Vector genome equivalents were also increased in TM-1 cells treated with MG132.
Increased FIV.GFP expression in the TM was also observed in MOCAS treated with 20
MUM MG132 and the high dose of vector. Vector genome equivalents were also
significantly increased in the MOCAS tissues. Increased transduction was not seen
with the low dose of virus. Conclusions: Proteasome inhibition increased the
transduction efficiency of FIV particles in TM-1 cells and MOCAS and may be a
useful adjunct for delivery of therapeutic genes to the TM by lentiviral vectors.
PMID- 29340647
TI - Fixation Instability: A New Measure of Neurologic Dysfunction in Multiple
Sclerosis.
PMID- 29340648
TI - A Novel Strategy for Quantifying Choriocapillaris Flow Voids Using Swept-Source
OCT Angiography.
AB - Purpose: To achieve reproducible imaging of the choriocapillaris and associated
flow voids using swept-source OCT angiography (SS-OCTA). Methods: Subjects were
enrolled and SS-OCTA was performed using the 3 * 3 mm scan pattern. Blood flow
was identified using the complex optical microangiography (OMAG) algorithm. The
choriocapillaris was defined as a slab from the outer boundary of Bruch's
membrane (BM) to approximately 20 MUm below BM. Compensation for the shadowing
effect caused by the RPE and BM complex on the choriocapillaris angiogram was
achieved by using the structural information from the same slab. A thresholding
method to calculate the percentage of flow voids from a region was developed
based on a normal database. Results: Twenty normal subjects and 12 subjects with
drusen were enrolled. SS-OCTA identified the choriocapillaris in normal subjects
as a lobular plexus of capillaries in the central macula and the lobular
arrangement became more evident toward the periphery. In all eyes, signal
compensation resulted in fewer choriocapillaris flow voids with improved
repeatability of measurements. The best repeatability for the measurement was
achieved by using 1 standard deviation (SD) for the thresholding strategy.
Conclusions: SS-OCTA can image the choriocapillaris in vivo, and the
repeatability of flow void measurements is high in the presence of drusen. The
ability to image the choriocapillaris and associated flow voids should prove
useful in understanding disease onset, progression, and response to therapies.
PMID- 29340649
TI - Optic Nerve Regeneration After Crush Remodels the Injury Site: Molecular Insights
From Imaging Mass Spectrometry.
AB - Purpose: Mammalian central nervous system axons fail to regenerate after injury.
Contributing factors include limited intrinsic growth capacity and an inhibitory
glial environment. Inflammation-induced optic nerve regeneration (IIR) is thought
to boost retinal ganglion cell (RGC) intrinsic growth capacity through progrowth
gene expression, but effects on the inhibitory glial environment of the optic
nerve are unexplored. To investigate progrowth molecular changes associated with
reactive gliosis during IIR, we developed an imaging mass spectrometry (IMS)
based approach that identifies discriminant molecular signals in and around optic
nerve crush (ONC) sites. Methods: ONC was performed in rats, and IIR was
established by intravitreal injection of a yeast cell wall preparation. Optic
nerves were collected at various postcrush intervals, and longitudinal sections
were analyzed with matrix-assisted laser desorption/ionization (MALDI) IMS and
data mining. Immunohistochemistry and confocal microscopy were used to compare
discriminant molecular features with cellular features of reactive gliosis.
Results: IIR increased the area of the crush site that was occupied by a dense
cellular infiltrate and mass spectral features consistent with lysosome-specific
lipids. IIR also increased immunohistochemical labeling for microglia and
macrophages. IIR enhanced clearance of lipid sulfatide myelin-associated
inhibitors of axon growth and accumulation of simple GM3 gangliosides in a
spatial distribution consistent with degradation of plasma membrane from
degenerated axons. Conclusions: IIR promotes a robust phagocytic response that
improves clearance of myelin and axon debris. This growth-permissive molecular
remodeling of the crush injury site extends our current understanding of IIR to
include mechanisms extrinsic to the RGC.
PMID- 29340650
TI - Colocalization of Galectin-3 With CD147 Is Associated With Increased
Gelatinolytic Activity in Ulcerating Human Corneas.
AB - Purpose: Galectin-3 is a carbohydrate-binding protein known to promote expression
of matrix metalloproteinases, a hallmark of ulceration, through interaction with
the extracellular matrix metalloproteinase inducer CD147. The aim of this study
was to investigate the distribution of galectin-3 in corneas of patients with
ulcerative keratitis and to determine its relationship to CD147 and the presence
of gelatinolytic activity. Methods: This was an observational case series
involving donor tissue from 13 patients with active corneal ulceration and 6
control corneas. Fixed-frozen sections of the corneas were processed to localize
galectin-3 and CD147 by immunofluorescence microscopy. Gelatinolytic activity was
detected by in situ zymography. Results: Tissue from patients with active corneal
ulceration showed a greater galectin-3 immunoreactivity in basal epithelia and
stroma compared with controls. Immunofluorescence grading scores revealed
increased colocalization of galectin-3 and CD147 in corneal ulcers at the
epithelial-stromal junction and within fibroblasts. Quantitative analysis using
the Manders' colocalization coefficient demonstrated significant overlap in
corneas from patients with ulcerative keratitis (M1 = 0.29; M2 = 0.22) as opposed
to control corneas (M1 = 0.01, P < 0.01; M2 = 0.02, P < 0.05). In these
experiments, there was a significant positive correlation between the degree of
galectin-3 and CD147 colocalization and the presence of gelatinolytic activity.
Conclusions: Our results indicate that concomitant stimulation and colocalization
of galectin-3 with CD147 are associated with increased gelatinolytic activity in
the actively ulcerating human cornea and suggest a mechanism by which galectin-3
may contribute to the degradation of extracellular matrix proteins during
ulceration.
PMID- 29340651
TI - Macular Perfusion Parameters in Different Angiocube Sizes: Does The Size Matter
in Quantitative Optical Coherence Tomography Angiography?
AB - Purpose: To investigate the macular quantitative parameters interchangeability of
three different optical coherence tomography angiography (OCT-A) angiocubes
(i.e., 3 * 3, 6 * 6, and 12 * 12 mm) on healthy subjects and patients affected by
diabetic retinopathy (DR) and to assess the interrater reliability of such
indices across the different scan protocols. Methods: Retrospective study
involving 20 eyes of healthy subjects and 20 eyes with DR. All eyes underwent
swept-source OCT-A with 3 * 3-, 6 * 6-, and 12 * 12-mm angiocubes centered on the
fovea. Foveal avascular zone (FAZ) area and vessel density on 3 * 3-, 6 * 6-, and
12 * 12-mm macular scans were calculated by three independent operators at all
retina, superficial, deep, and choriocapillary vascular layers.
Interchangeability and interrater reliabilities were estimated using intraclass
correlation coefficient (ICC). Results: Interscan reproducibility of FAZ area was
very strong (ICC > 0.85) at every plexus. On the contrary, vessel density values
significantly varied across different scan sizes (ICC < 0.51). Intrascan
interrater reliability was high for all retina and superficial FAZ areas, while
it was satisfactory at deep capillary plexus only for 3 * 3-mm scan. Conclusions:
FAZ area at all plexuses is a robust parameter even if calculated on angiocubes
with different size. However, interrater reliability is higher when measured in
smaller scans. Conversely, vessel density results depend on the size of
angiocube, although their interrater reliability is extremely high. Studies
involving OCT-A should take into consideration that scan size may influence
macular perfusion parameters and interrater reliability.
PMID- 29340652
TI - Pain Sensitivity Associated With the Length of the Maximum Interblink Period.
AB - Purpose: Pain sensitivity has been identified as a factor that affects how
individuals answer dry eye questionnaires, but it is unknown how it affects
ocular discomfort. This study used the time that individuals could refrain from
blinking as an indicator of ocular discomfort and set out to determine whether it
was related to pain sensitivity, while adjusting for ocular surface conditions.
Methods: Subjects first completed the Pain Sensitivity Questionnaire to quantify
pain sensitivity levels. Exposed interpalpebral area, tear meniscus height, tear
film lipid layer thickness, ocular surface cooling, and noninvasive tear breakup
were assessed. Subjects were then asked to refrain from blinking until the
initial onset of discomfort, which was termed "the maximum interblink period"
(MIBP), while ocular surface cooling rate was simultaneously measured. Subjects
were seen for four visits over a course of 2 days. Results: Forty-two subjects
(36 females, 6 males) completed the study, with a mean (SD) age of 23.2 (3.8)
years. A longer MIBP was associated with decreased pain sensitivity (P = 0.04),
lower ocular surface cooling rate (P < 0.001), and Asian ethnicity (P = 0.005).
Based on the results from the mixed-effect model, it is estimated that
individuals would be able to refrain from blinking for an additional 4 seconds if
they had the lowest (0.6) compared to the highest (6.1) pain sensitivity in the
study cohort. Conclusions: The Pain Sensitivity Questionnaire was associated with
the MIBP length even after adjusting for ocular surface conditions, which
suggests that pain sensitivity plays a role in influencing how ocular discomfort
is perceived.
PMID- 29340653
TI - ATTED-II in 2018: A Plant Coexpression Database Based on Investigation of the
Statistical Property of the Mutual Rank Index.
PMID- 29340654
TI - Antioxidant, angiotensin-converting enzyme inhibitory activity and other
functional properties of egg white proteins and their derived peptides - A
review.
AB - Egg white contains many functionally important proteins: ovalbumin (54%),
ovotransferrin (12%), ovomucoid (11%), ovoglobulin (G2 and G3, 8%), ovomucin
(3.5%), and lysozyme (3.5%) are major proteins, while ovoinhibitors,
ovomacroglobulin, ovoglycoprotein, ovoflavoprotein, thiamine-binding proteins,
and avidin are minor proteins present in egg white. These proteins, as well as
the peptides derived from the proteins, have been recognized for their functional
importance as antioxidant, antimicrobial, metal-chelating, anti-viral, anti
tumour, and angiotensin-converting enzyme (ACE)-inhibitory activities. Among the
functional properties of the peptides, antioxidant and antimicrobial activities
are important characteristics for food processing while other properties such as
ACE-inhibitory activity of the peptides can have important health-related
functionalities. Bioactive peptides can be produced from egg white proteins by
enzyme hydrolysis, chemical treatments, or thermal treatments at different pH
conditions. The effective functional peptides produced from egg white proteins
are usually smaller than 2 kDa in molecular size. However, these peptides are
known for their beneficial activities in vitro only, and little work has been
done to prove their beneficial effects in vivo. Therefore, further studies are
needed to see if the bioactive peptides derived from egg white proteins are
helpful for humans in the future.
PMID- 29340655
TI - Effect of dietary synbiotic supplement on behavioral patterns and growth
performance of broiler chickens reared under heat stress.
AB - This study examined the effects of a dietary synbiotic supplement on the
behavioral patterns and growth performance of broiler chickens exposed to heat
stress (HS). Three hundred sixty 1-day-old male Ross 708 broiler chicks were
distributed among 24 floor pens (15 chicks per pen); each pen was randomly
assigned to one of 3 dietary treatments containing a synbiotic at 0 (control),
0.5 (0.5X) and 1.0 (1.0X) g/kg. From d 15 to 42, birds were exposed to HS at 32
degrees C daily from 08:00 to 17:00. Five broiler chickens were randomly marked
in each pen for behavioral observation. Instantaneous scan sampling was used to
record the birds' behavioral patterns. Performance parameters were measured on d
7, 14, 28 and 42. The synbiotic fed birds exhibited more standing, sitting,
walking, feeding, preening and less wing spreading and panting behaviors (P <
0.05) compared to birds fed the control diet. The synbiotic group also had higher
BW, BW gain and feed intake on d 7, 14 and 42 (P < 0.05), and higher BW, feed
intake and feed conversion ratio at d 28 (P < 0.01). There were no treatment
effects on drinking behavior, BW gain on d 28 and feed conversion ratio on d 42
(P > 0.05). There were few dose-related differences of the synbiotic on
production performance; namely, the 1.0X concentration resulted in the highest BW
and feed intake on d 14 and 42 (P < 0.05), while BW gain was higher compared to
the control group only on d 42 (P < 0.05). The results suggest that the synbiotic
supplement may prove to be an important management tool for the broiler industry
to diminish the negative effects of HS, potentially safeguarding the welfare and
production of broiler chickens, particularly in areas that experience hot
climates.
PMID- 29340656
TI - Antagonistic effect of Saccharomyces cerevisiae KTP and Issatchenkia occidentalis
ApC on hyphal development and adhesion of Candida albicans.
AB - The morphological transition from yeast to a hyphal form, as well as the adhesion
capability to the gastrointestinal tract, are implicated virulent determinant in
Candida albicans and could be potential targets for prevention of the
opportunistic pathogen. Based on this rationale, two yeast strains Saccharomyces
cerevisiae KTP and Issatchenkia occidentalis ApC along with reference strain
Saccharomyces boulardii NCDC 363 were screened for the probiotic potential.
Characters like pH, temperature, bile, simulated gastrointestinal juice tolerance
tests, and Caco-2 cell line adhesion assay were determined in the present study.
Further, the evaluation of its impact on C. albicans morphological transition and
adhesion was assessed using microtitre germ tube test. In terms of probiotic
characteristics, both the strains were tolerant to pH 2.5 and the presence of
bile (0.3 to 0.6%) with an optimum growth temperature of 37 degrees C. The strain
KTP was also resistant to simulated gastric and intestinal juices as compared to
control (13% and 41%, respectively) and NCDC 363 (55% and 35%, respectively). In
contrast, both the yeasts had reduced adhesiveness to Caco-2 monolayer. Candida
virulence in in vitro systems indicated that treatment of live probiotic yeast
cells (108 ml) effectively reduced the filamentation and adhesion of C. albicans.
The S. cerevisiae KTP had a profound effect on the hyphal development and
adhesion when compared to the ApC and NCDC 363. The strain significantly reduced
(P < .05) the hyphal growth in co-cultivated (93% and 94%, respectively) and pre
existing hyphae (54% and 68%) of strains C. albicans 183 and 1151. Isolates KTP
and ApC also reduced the adhesion (~ 22% and 41%, respectively) and transition of
blastoconidia at two hours of incubation in abiotic surface. This study provides
knowledge on the effect of potential probiotic yeasts such as Saccharomyces and
non- Saccharomyces strains against virulence characteristic of Candida albicans.
PMID- 29340657
TI - Ixodes scapularis (Acari: Ixodidae) Reservoir Host Diversity and Abundance
Impacts on Dilution of Borrelia burgdorferi (Spirochaetales: Spirochaetaceae) in
Residential and Woodland Habitats in Connecticut, United States.
AB - The dilution effect in the zoonotic disease transmission cycle theorizes that an
increased diversity of host species will alter transmission dynamics, result in a
decrease in pathogen prevalence, and potentially lower human disease incidence.
The interrelationship of Borrelia burgdorferi (Johnson, Schmid, Hyde,
Steigerwalt, and Brenner) (Spirochaetales: Spirochaetaceae), the etiological
agent of Lyme disease (LD), and its primary vector, blacklegged ticks (Ixodes
scapularis Say) (Acari: Ixodidae), is a commonly used example of the dilution
effect, suggesting that an increased diversity of host species will be found in
large, undisturbed forested tracts and lower diversity in fragmented forests.
Given that Connecticut woodlands are mature with heavy upper canopies and
generally poor habitat quality, we hypothesized there would be higher diversity
of host species resulting in lower prevalence of B. burgdorferi in white-footed
mice (Peromyscus leucopus Rafinesque) (Rodentia: Cricetidae) in forested
residential areas. Using camera and live small mammal trapping techniques, we
determined there was a greater richness of reservoir host species, significantly
higher encounters with hosts, and significantly lower B. burgdorferi host
infection in residential areas as compared to large, intact forested stands.
Furthermore, we determined that the driving factor of pathogen dilution was not
host species diversity, but rather overall encounter abundance with alternative
hosts, regardless of habitat type. Our study challenges major concepts of the
dilution effect within the Connecticut landscape and calls for new managerial
actions to address the current state of our woodlands and abundance of host
species in the interest of both forest and public health.
PMID- 29340658
TI - Cuticle and pore plug properties in the table egg.
AB - Food safety of table eggs is vital since many pathogens can contaminate the
unfertilized egg, leading to increased risk of foodborne illness for consumers.
The eggshell cuticle is the first line of defense to restrict the entry of egg
associated pathogens, such as Salmonella Enteritidis. The thickness and
completeness of coverage of the cuticle layer are heritable traits that are
strongly associated with egg resistance to bacterial penetration. The present
study characterizes the chemical composition of the eggshell cuticle and
structure of pore plugs from table eggs. Eggs collected from both brown and white
egg laying Lohmann flocks (early, mid, and late lay) were either unwashed or
washed. Pore plugs were characterized using scanning electron microscopy (SEM),
and elemental composition was determined using energy-dispersive x-ray
spectroscopy (EDS). SEM observations confirmed that the plug formed by the
cuticle layer within the eggshell pore remains firmly lodged throughout the
commercial washing process. The eggshell thickness and cuticle pore length
visualized in brown eggs was significantly higher than in white eggs in hens of
all ages. EDS analysis revealed that the pore inner surface was enriched in
phosphorus and chemically different from the surrounding bulk eggshell mineral.
Detailed assessment of the cuticle chemical composition was performed by Fourier
transform infrared spectroscopy (FTIR). Washing of eggs removed cuticle from the
eggshell surface. There was a trend of lower cuticle coverage with increasing hen
age for white eggs. A significant reduction in the amount of proteins and
phosphates and polysaccharides was observed in the cuticle of brown unwashed eggs
with hen age. In white unwashed eggs, amides and lipids decreased with hen age;
by contrast, the amount of sulfate was highest at mid-lay. The results from our
research will assist selective breeding programs that target cuticle integrity
and pore plug stability to enhance egg resistance to pathogen penetration and
improve food safety.
PMID- 29340659
TI - Comparing the Outcomes of Sleeve Gastrectomy and Roux-en-Y Gastric Bypass for
Severe Obesity.
PMID- 29340660
TI - Reimagining Obesity in 2018: A JAMA Theme Issue on Obesity.
PMID- 29340661
TI - Second Cancer Biosimilar Approved.
PMID- 29340662
TI - Regulatory Pathway for 3D Printing.
PMID- 29340663
TI - Monthly Buprenorphine Injection Approved for Opioid Use Disorder.
PMID- 29340664
TI - Long-term Outcomes Following Bariatric Surgery.
PMID- 29340665
TI - Medical Care Use and Expenditures Associated With Adult Obesity in the United
States.
PMID- 29340667
TI - Appropriations for City Health Departments.
PMID- 29340668
TI - Axillary vs Sentinel Lymph Node Dissection in Women With Invasive Breast Cancer.
PMID- 29340669
TI - Risks of Statins for Lower-Risk Individuals.
PMID- 29340670
TI - Trends in Carotid Revascularization Procedures.
PMID- 29340671
TI - Trends in Carotid Revascularization Procedures.
PMID- 29340672
TI - Axillary vs Sentinel Lymph Node Dissection in Women With Invasive Breast Cancer
Reply.
PMID- 29340673
TI - Risks of Statins for Lower-Risk Individuals-Reply.
PMID- 29340674
TI - Trends in Carotid Revascularization Procedures-Reply.
PMID- 29340675
TI - Interest in the Ketogenic Diet Grows for Weight Loss and Type 2 Diabetes.
PMID- 29340676
TI - Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric
Bypass on Weight Loss at 5 Years Among Patients With Morbid Obesity: The
SLEEVEPASS Randomized Clinical Trial.
AB - Importance: Laparoscopic sleeve gastrectomy for treatment of morbid obesity has
increased substantially despite the lack of long-term results compared with
laparoscopic Roux-en-Y gastric bypass. Objective: To determine whether
laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass are
equivalent for weight loss at 5 years in patients with morbid obesity. Design,
Setting, and Participants: The Sleeve vs Bypass (SLEEVEPASS) multicenter,
multisurgeon, open-label, randomized clinical equivalence trial was conducted
from March 2008 until June 2010 in Finland. The trial enrolled 240 morbidly obese
patients aged 18 to 60 years, who were randomly assigned to sleeve gastrectomy or
gastric bypass with a 5-year follow-up period (last follow-up, October 14, 2015).
Interventions: Laparoscopic sleeve gastrectomy (n = 121) or laparoscopic Roux-en
Y gastric bypass (n = 119). Main Outcomes and Measures: The primary end point was
weight loss evaluated by percentage excess weight loss. Prespecified equivalence
margins for the clinical significance of weight loss differences between gastric
bypass and sleeve gastrectomy were -9% to +9% excess weight loss. Secondary end
points included resolution of comorbidities, improvement of quality of life
(QOL), all adverse events (overall morbidity), and mortality. Results: Among 240
patients randomized (mean age, 48 [SD, 9] years; mean baseline body mass index,
45.9, [SD, 6.0]; 69.6% women), 80.4% completed the 5-year follow-up. At baseline,
42.1% had type 2 diabetes, 34.6% dyslipidemia, and 70.8% hypertension. The
estimated mean percentage excess weight loss at 5 years was 49% (95% CI, 45%-52%)
after sleeve gastrectomy and 57% (95% CI, 53%-61%) after gastric bypass
(difference, 8.2 percentage units [95% CI, 3.2%-13.2%], higher in the gastric
bypass group) and did not meet criteria for equivalence. Complete or partial
remission of type 2 diabetes was seen in 37% (n = 15/41) after sleeve gastrectomy
and in 45% (n = 18/40) after gastric bypass (P > .99). Medication for
dyslipidemia was discontinued in 47% (n = 14/30) after sleeve gastrectomy and 60%
(n = 24/40) after gastric bypass (P = .15) and for hypertension in 29% (n =
20/68) and 51% (n = 37/73) (P = .02), respectively. There was no statistically
significant difference in QOL between groups (P = .85) and no treatment-related
mortality. At 5 years the overall morbidity rate was 19% (n = 23) for sleeve
gastrectomy and 26% (n = 31) for gastric bypass (P = .19). Conclusions and
Relevance: Among patients with morbid obesity, use of laparoscopic sleeve
gastrectomy compared with use of laparoscopic Roux-en-Y gastric bypass did not
meet criteria for equivalence in terms of percentage excess weight loss at 5
years. Although gastric bypass compared with sleeve gastrectomy was associated
with greater percentage excess weight loss at 5 years, the difference was not
statistically significant, based on the prespecified equivalence margins. Trial
Registration: clinicaltrials.gov Identifier: NCT00793143.
PMID- 29340677
TI - Association of Bariatric Surgery Using Laparoscopic Banding, Roux-en-Y Gastric
Bypass, or Laparoscopic Sleeve Gastrectomy vs Usual Care Obesity Management With
All-Cause Mortality.
AB - Importance: Bariatric surgery is an effective and safe approach for weight loss
and short-term improvement in metabolic disorders such as diabetes. However,
studies have been limited in most settings by lack of a nonsurgical group, losses
to follow-up, missing data, and small sample sizes in clinical trials and
observational studies. Objective: To assess the association of 3 common types of
bariatric surgery compared with nonsurgical treatment with mortality and other
clinical outcomes among obese patients. Design, Setting, and Participants:
Retrospective cohort study in a large Israeli integrated health fund covering 54%
of Israeli citizens with less than 1% turnover of members annually. Obese adult
patients who underwent bariatric surgery between January 1, 2005, and December
31, 2014, were selected and compared with obese nonsurgical patients matched on
age, sex, body mass index (BMI), and diabetes, with a final follow-up date of
December 31, 2015. A total of 33 540 patients were included in this study.
Exposures: Bariatric surgery (laparoscopic banding, Roux-en-Y gastric bypass, or
laparoscopic sleeve gastrectomy) or usual care obesity management only (provided
by a primary care physician and which may include dietary counseling and behavior
modification). Main Outcomes and Measures: The primary outcome, all-cause
mortality, matched and adjusted for BMI prior to surgery, age, sex, socioeconomic
status, diabetes, hyperlipidemia, hypertension, cardiovascular disease, and
smoking. Results: The study population included 8385 patients who underwent
bariatric surgery (median age, 46 [IQR, 37-54] years; 5490 [65.5%] women;
baseline median BMI, 40.6 [IQR, 38.5-43.7]; laparoscopic banding [n = 3635],
gastric bypass [n = 1388], laparoscopic sleeve gastrectomy [n = 3362], and 25 155
nonsurgical matched patients (median age, 46 [IQR, 37-54] years; 16 470 [65.5%]
women; baseline median BMI, 40.5 [IQR, 37.0-43.5]). The availability of follow-up
data was 100% for all-cause mortality. There were 105 deaths (1.3%) among
surgical patients during a median follow-up of 4.3 (IQR, 2.8-6.6) years
(including 61 [1.7%] who underwent laparoscopic banding, 18 [1.3%] gastric
bypass, and 26 [0.8%] sleeve gastrectomy), and 583 deaths (2.3%) among
nonsurgical patients during a median follow-up of 4.0 (IQR, 2.6-6.2) years. The
absolute difference was 2.51 (95% CI, 1.86-3.15) fewer deaths/1000 person-years
in the surgical vs nonsurgical group. Adjusted hazard ratios (HRs) for mortality
among nonsurgical vs surgical patients were 2.02 (95% CI, 1.63-2.52) for the
entire study population; by surgical type, HRs were 2.01 (95% CI, 1.50-2.69) for
laparoscopic banding, 2.65 (95% CI, 1.55-4.52) for gastric bypass, and 1.60 (95%
CI, 1.02-2.51) for laparoscopic sleeve gastrectomy. Conclusions and Relevance:
Among obese patients in a large integrated health fund in Israel, bariatric
surgery using laparoscopic banding, gastric bypass, or laparoscopic sleeve
gastrectomy, compared with usual care nonsurgical obesity management, was
associated with lower all-cause mortality over a median follow-up of
approximately 4.5 years. The evidence of this association adds to the limited
literature describing beneficial outcomes of these 3 types of bariatric surgery
compared with usual care obesity management alone.
PMID- 29340678
TI - Lifestyle Intervention and Medical Management With vs Without Roux-en-Y Gastric
Bypass and Control of Hemoglobin A1c, LDL Cholesterol, and Systolic Blood
Pressure at 5 Years in the Diabetes Surgery Study.
AB - Importance: The Roux-en-Y gastric bypass is effective in achieving established
diabetes treatment targets, but durability is unknown. Objective: To compare
durability of Roux-en-Y gastric bypass added to intensive lifestyle and medical
management in achieving diabetes control targets. Design, Setting, and
Participants: Observational follow-up of a randomized clinical trial at 4 sites
in the United States and Taiwan, involving 120 participants who had a hemoglobin
A1c (HbA1c) level of 8.0% or higher and a body mass index between 30.0 and 39.9
(enrolled between April 2008 and December 2011) were followed up for 5 years,
ending in November 2016. Interventions: Lifestyle-intensive medical management
intervention based on the Diabetes Prevention Program and LookAHEAD trials for 2
years, with and without (60 participants each) Roux-en-Y gastric bypass surgery
followed by observation to year 5. Main Outcomes and Measures: The American
Diabetes Association composite triple end point of hemoglobin A1c less than 7.0%,
low-density lipoprotein cholesterol less than 100 mg/dL, and systolic blood
pressure less than 130 mm Hg at 5 years. Results: Of 120 participants who were
initially randomized (mean age, 49 years [SD, 8 years], 72 women [60%]), 98 (82%)
completed 5 years of follow-up. Baseline characteristics were similar between
groups: mean (SD) body mass index 34.4 (3.2) for the lifestyle-medical management
group and 34.9 (3.0) for the gastric bypass group and had hemoglobin A1c levels
of 9.6% (1.2) and 9.6% (1.0), respectively. At 5 years, 13 participants (23%) in
the gastric bypass group and 2 (4%) in the lifestyle-intensive medical management
group had achieved the composite triple end point (difference, 19%; 95% CI, 4%
34%; P = .01). In the fifth year, 31 patients (55%) in the gastric bypass group
vs 8 (14%) in the lifestyle-medical management group achieved an HbA1c level of
less than 7.0% (difference, 41%; 95% CI, 19%-63%; P = .002). Gastric bypass had
more serious adverse events than did the lifestyle-medical management
intervention, 66 events vs 38 events, most frequently gastrointestinal events and
surgical complications such as strictures, small bowel obstructions, and leaks.
Gastric bypass had more parathyroid hormone elevation but no difference in B12
deficiency. Conclusions and Relevance: In extended follow-up of obese adults with
type 2 diabetes randomized to adding gastric bypass compared with lifestyle and
intensive medical management alone, there remained a significantly better
composite triple end point in the surgical group at 5 years. However, because the
effect size diminished over 5 years, further follow-up is needed to understand
the durability of the improvement. Trial Registration: clinicaltrials.gov
Identifier: NCT00641251.
PMID- 29340679
TI - Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric
Bypass on Weight Loss in Patients With Morbid Obesity: The SM-BOSS Randomized
Clinical Trial.
AB - Importance: Sleeve gastrectomy is increasingly used in the treatment of morbid
obesity, but its long-term outcome vs the standard Roux-en-Y gastric bypass
procedure is unknown. Objective: To determine whether there are differences
between sleeve gastrectomy and Roux-en-Y gastric bypass in terms of weight loss,
changes in comorbidities, increase in quality of life, and adverse events.
Design, Setting, and Participants: The Swiss Multicenter Bypass or Sleeve Study
(SM-BOSS), a 2-group randomized trial, was conducted from January 2007 until
November 2011 (last follow-up in March 2017). Of 3971 morbidly obese patients
evaluated for bariatric surgery at 4 Swiss bariatric centers, 217 patients were
enrolled and randomly assigned to sleeve gastrectomy or Roux-en-Y gastric bypass
with a 5-year follow-up period. Interventions: Patients were randomly assigned to
undergo laparoscopic sleeve gastrectomy (n = 107) or laparoscopic Roux-en-Y
gastric bypass (n = 110). Main Outcomes and Measures: The primary end point was
weight loss, expressed as percentage excess body mass index (BMI) loss.
Exploratory end points were changes in comorbidities and adverse events. Results:
Among the 217 patients (mean age, 45.5 years; 72% women; mean BMI, 43.9) 205
(94.5%) completed the trial. Excess BMI loss was not significantly different at 5
years: for sleeve gastrectomy, 61.1%, vs Roux-en-Y gastric bypass, 68.3%
(absolute difference, -7.18%; 95% CI, -14.30% to -0.06%; P = .22 after adjustment
for multiple comparisons). Gastric reflux remission was observed more frequently
after Roux-en-Y gastric bypass (60.4%) than after sleeve gastrectomy (25.0%).
Gastric reflux worsened (more symptoms or increase in therapy) more often after
sleeve gastrectomy (31.8%) than after Roux-en-Y gastric bypass (6.3%). The number
of patients with reoperations or interventions was 16/101 (15.8%) after sleeve
gastrectomy and 23/104 (22.1%) after Roux-en-Y gastric bypass. Conclusions and
Relevance: Among patients with morbid obesity, there was no significant
difference in excess BMI loss between laparoscopic sleeve gastrectomy and
laparoscopic Roux-en-Y gastric bypass at 5 years of follow-up after surgery.
Trial Registration: clinicaltrials.gov Identifier: NCT00356213.
PMID- 29340681
TI - Sleeve Gastrectomy for Weight Loss.
PMID- 29340680
TI - Association of Bariatric Surgery vs Medical Obesity Treatment With Long-term
Medical Complications and Obesity-Related Comorbidities.
AB - Importance: The association of bariatric surgery and specialized medical obesity
treatment with beneficial and detrimental outcomes remains uncertain. Objective:
To compare changes in obesity-related comorbidities in patients with severe
obesity (body mass index >=40 or >=35 and at least 1 comorbidity) undergoing
bariatric surgery or specialized medical treatment. Design, Setting, and
Participants: Cohort study with baseline data of exposures from November 2005
through July 2010 and follow-up data from 2006 until death or through December
2015 at a tertiary care outpatient center, Vestfold Hospital Trust, Norway.
Consecutive treatment-seeking adult patients (n = 2109) with severe obesity
assessed (221 patients excluded and 1888 patients included). Exposures: Bariatric
surgery (n = 932, 92% gastric bypass) or specialized medical treatment (n = 956)
including individual or group-based lifestyle intervention programs. Main
Outcomes and Measures: Primary outcomes included remission and new onset of
hypertension based on drugs dispensed according to the Norwegian Prescription
Database. Prespecified secondary outcomes included changes in comorbidities.
Adverse events included complications retrieved from the Norwegian Patient
Registry and a local laboratory database. Results: Among 1888 patients included
in the study, the mean (SD) age was 43.5 (12.3) years (1249 women [66%]; mean
[SD] baseline BMI, 44.2 [6.1]; 100% completed follow-up at a median of 6.5 years
[range, 0.2-10.1]). Surgically treated patients had a greater likelihood of
remission and lesser likelihood for new onset of hypertension (remission:
absolute risk [AR], 31.9% vs 12.4%); risk difference [RD], 19.5% [95% CI, 15.8%
23.2%], relative risk [RR], 2.1 [95% CI, 2.0-2.2]; new onset: AR, 3.5% vs 12.2%,
RD, 8.7% [95% CI, 6.7%-10.7%], RR, 0.4 [95% CI, 0.3-0.5]; greater likelihood of
diabetes remission: AR, 57.5% vs 14.8%; RD, 42.7% [95% CI, 35.8%-49.7%], RR, 3.9
[95% CI, 2.8-5.4]; greater risk of new-onset depression: AR, 8.9% vs 6.5%; RD,
2.4% [95% CI, 1.3%-3.5%], RR, 1.5 [95% CI, 1.4-1.7]; and treatment with opioids:
AR, 19.4% vs 15.8%, RD, 3.6% [95% CI, 2.3%-4.9%], RR, 1.3 [95% CI, 1.2-1.4]).
Surgical patients had a greater risk for undergoing at least 1 additional
gastrointestinal surgical procedure (AR, 31.3% vs 15.5%; RD, 15.8% [95% CI, 13.1%
18.5%]; RR, 2.0 [95% CI, 1.7-2.4]). The proportion of patients with low ferritin
levels was significantly greater in the surgical group (26% vs 12%, P < .001).
Conclusions and Relevance: Among patients with severe obesity followed up for a
median of 6.5 years, bariatric surgery compared with medical treatment was
associated with a clinically important increased risk for complications, as well
as lower risks of obesity-related comorbidities. The risk for complications
should be considered in the decision-making process.
PMID- 29340684
TI - Evolving Societal Norms of Obesity: What Is the Appropriate Response?
PMID- 29340685
TI - Can the Government Require Health Warnings on Sugar-Sweetened Beverage
Advertisements?
PMID- 29340686
TI - Taxes and Sugar-Sweetened Beverages.
PMID- 29340687
TI - Toward Precision Approaches for the Prevention and Treatment of Obesity.
PMID- 29340688
TI - Counting Calories as an Approach to Achieve Weight Control.
PMID- 29340689
TI - Fitness or Fatness: Which Is More Important?
PMID- 29340690
TI - Possible Biomarkers of Deadly Ebola.
PMID- 29340691
TI - Dangers of Substandard or Falsified Medicines.
PMID- 29340692
TI - Combination Strategy Associated With Reduced HIV Incidence in Uganda.
PMID- 29340693
TI - Can granulomatosis with polyangiitis be diagnosed earlier in primary care? A case
control study.
AB - Background: People with granulomatosis with polyangiitis (GPA) commonly described
long delays before diagnosis. Aim: To study the natural history of GPA prior to
diagnosis using primary care data, and determine whether clinical features could
be identified to help earlier diagnosis. Design: Case-control study using the
Clinical Practice Research Datalink. Methods: We compared primary care activity
and clinical features between cases and 10 matched controls. Results: We
identified 757 cases and matched 7546 controls. Compared to controls, cases had
more GP consultations and overall healthcare activity in the 5 years prior to
their diagnosis, with a marked increase in the year before diagnosis, and
particularly in the last 3 months. However, consultations were mostly for
symptoms that were not specifically related to GPA. In the year prior to
diagnosis, the most frequent and strongly predictive clinical features of GPA
were Ear Nose and Throat (ENT) symptoms [34.5% of cases, odds ratio (OR) 10.5,
95% confidence intervals (CI) 8.6-12.7], and general (constitutional) symptoms
(21.5% of cases, OR 9.0, 95% CI 7.1-11.3). In the year before diagnosis a larger
number of cases attended secondary care (382, 50.5%) than had records of clinical
features of GPA. Conclusions: After discussing our findings, we conclude that it
would be difficult to identify cases of GPA earlier in primary care. Our results
support a need for heightened awareness of this condition among secondary care
clinicians, especially those assessing emergency admissions, and in the clinics
which were most frequently attended by cases 3-12 months prior to diagnosis.
PMID- 29340694
TI - Death row prisoners-regret for the past and fear for the future?
PMID- 29340696
TI - From Southeast Asia to the Sewers: Study Determines New Geographic Origins of
Brown Rats.
PMID- 29340695
TI - Development and psychometric properties of the Hookah Smoking Initiation for
Women Questionnaire (HIWQ).
AB - The aims of this study were to design the Hookah Smoking Initiation for Women
Questionnaire (HIWQ) and determine its psychometric properties. This was a
sequential exploratory mixed-methods design consisting of qualitative and
quantitative phases. This study was conducted from August 2012 to July 2013 in
Tehran. In the qualitative phase, semi-structured interviews were held with 36
Iranian women for developing a preliminary item pool. Consequently, during the
quantitative phase, the psychometric properties of the questionnaire were
determined with the collaboration of 323 women living in various geographical
locations in Tehran, Iran. Content validity of the questionnaire was examined by
a panel of experts. The questionnaire's construct validity was assessed using
exploratory factor analysis and confirmatory factor analyses. The Cronbach's
alpha coefficient was calculated to check the questionnaire's internal
consistency reliability. Moreover, its stability was tested using the test-retest
method. Exploratory factor analysis indicated that the HIQW could best be
explained by a six-factor solution: 'drawing the attention of other people', the
need to having fun and being relaxed, 'hookah smoking in the family',
'availability of hookah', 'curiosity' and 'having a positive attitude toward
hookah'. It also was found that the construct and content validity, and the
reliability of the questionnaire were satisfactory (alpha = 0.83, ICC = 0.94).
The HIQW was valid and reliable. Therefore, healthcare professionals can use it
for evaluating the hookah smoking initiation in women. Future studies are
required to refine this questionnaire and assess its applicability in different
cultures and contexts.
PMID- 29340697
TI - Genetic and clinical evidence of mitochondrial dysfunction in autism spectrum
disorder and intellectual disability.
AB - Clinical conditions commonly associated with mitochondrial disorders (CAMDs) are
often present in autism spectrum disorders (ASD) and intellectual disability
(ID). Therefore, the mitochondrial dysfunction hypothesis has been proposed as a
transversal mechanism that may function in both disorders. Here, we investigated
the presence of conditions associated with mitochondrial disorders and
mitochondrial DNA (mtDNA) alterations in 122 subjects who presented ASD with ID
(ASD group), 115 subjects who presented ID but not ASD (ID group) and 112 healthy
controls (HC group). We assessed in the three study groups the presence of the
clinical conditions through a questionnaire and the mtDNA content of two
mitochondrial genes, MT-ND1 and MT-ND4, by qPCR. The mtDNA sequences of 98 ASD
and 95 ID subjects were obtained by mtDNA-targeted next generation sequencing and
analysed through the MToolBox pipeline to identify mtDNA mutations. Subjects with
ASD and ID showed higher frequencies of constipation, edema, seizures, vision
alterations, strabismus and sphincter incontinence than HCs subjects. ASD and ID
subjects showed significantly lower mtDNA content than HCs in both MT-ND1 and MT
ND4 genes. In addition, we identified 49 putative pathogenic variants with a
heteroplasmy level higher than 60%: 8 missense, 29 rRNA and 12 tRNA variants. A
total of 28.6% of ASD and 30.5% of ID subjects carried at least one putative
pathogenic mtDNA mutation. The high frequency of CAMDs, the low mtDNA content and
the presence of putative pathogenic mtDNA mutations observed in both ASD and ID
subjects are evidence of mitochondrial dysfunction in ASD and ID.
PMID- 29340698
TI - Simultaneous detection of chicken cytokines in plasma samples using the Bio-Plex
assay.
AB - A chicken multiplex cytokine assay (Bio-Plex) to detect four different cytokines
(IL-2, IL-12, IL-10, and interferon gamma) simultaneously in plasma samples was
designed. Most standard curves range between 1 to 5 pg/mL and 5,000 pg/mL, except
for IFNgamma with the range of 50 to 25,000 pg/mL. Such a chicken multiplex assay
proved to be fast and reliable, and comparable in sensitivity, accuracy, and
reproducibility to conventional enzyme-linked immunosorbent assays. Comparison of
the multiplex assay with the ELISA technique using the same clones of detection
and capture antibodies resulted in correlation coefficients for all cytokines
ranging from 0.95 to 0.99. Lower limit of detection and limit of quantification
values were obtained for all tested cytokines by the Bio-Plex assay compared with
ELISA. To reduce the risk of cross-reaction with other proteins, the Bio-Plex
system was used, combining the principle of sandwich immunoassay with the Luminex
bead-based technology. The cytokine standard recoveries for each cytokine varied
between 86 and 118% in dynamic concentration ranges. A chicken multiplex cytokine
assay (Bio-Plex) provided a more complete picture of differences between the
Th1/Th2 cytokine profiles of the immunized via a new system of antigen delivery
into chicken antigen-presenting cells and control groups. This multiplexed
fluorescent-bead-based detection assay can be used as a quantitative or
comparative tool for the study of the chicken ex vivo cellular immune response.
PMID- 29340700
TI - Finding Their Inner Bird: Using Modern Genomics to Turn Alligator Scales into
Birdlike Feathers.
PMID- 29340699
TI - Long-term expression of glomerular genes in diabetic nephropathy.
AB - Background: Although diabetic nephropathy (DN) is the most common cause for end
stage renal disease in western societies, its pathogenesis still remains largely
unclear. A different gene pattern of diabetic and healthy kidney cells is one of
the probable explanations. Numerous signalling pathways have emerged as important
pathophysiological mechanisms for diabetes-induced renal injury. Methods:
Glomerular cells, as podocytes or mesangial cells, are predominantly involved in
the development of diabetic renal lesions. While many gene assays concerning DN
are performed with whole kidney or renal cortex tissue, we isolated glomeruli
from black and tan, brachyuric (BTBR) obese/obese (ob/ob) and wildtype mice at
four different timepoints (4, 8, 16 and 24 weeks) and performed an mRNA
microarray to identify differentially expressed genes (DEGs). In contrast to many
other diabetic mouse models, these homozygous ob/ob leptin-deficient mice develop
not only a severe type 2 diabetes, but also diabetic kidney injury with all the
clinical and especially histologic features defining human DN. By functional
enrichment analysis we were able to investigate biological processes and pathways
enriched by the DEGs at different disease stages. Altered expression of nine
randomly selected genes was confirmed by quantitative polymerase chain reaction
from glomerular RNA. Results: Ob/ob type 2 diabetic mice showed up- and
downregulation of genes primarily involved in metabolic processes and pathways,
including glucose, lipid, fatty acid, retinol and amino acid metabolism. Members
of the CYP4A and ApoB family were found among the top abundant genes. But more
interestingly, altered gene loci showed enrichment for processes and pathways
linked to angioneogenesis, complement cascades, semaphorin pathways, oxidation
and reduction processes and renin secretion. Conclusion: The gene profile of BTBR
ob/ob type 2 diabetic mice we conducted in this study can help to identify new
key players in molecular pathogenesis of diabetic kidney injury.
PMID- 29340701
TI - Impact of graft loss among kidney diseases with a high risk of post-transplant
recurrence in the paediatric population.
PMID- 29340702
TI - Risk and Protective Factors for Depressive Symptoms Among African American Men:
An Application of the Stress Process Model.
AB - Objectives: This study employs the stress process model (SPM) to identify
risk/protective factors for mental health among adult African American men.
Method: Using a community-based sample of Miami, FL residents linked to
neighborhood Census data, this study identifies risk/protective factors for
depressive symptomatology using a sample of 248 adult African American men.
Results: The stress process variables independently associated with depressive
symptoms were family support, mastery, self-esteem, chronic stressors, and daily
discrimination. While mastery and self-esteem mediated the relationship between
neighborhood income and depressive symptoms, perceived family support served as a
buffer for stress exposure. Collectively, the SPM explains nearly half of the
variability in depressive symptoms among African American men. Discussion: The
SPM is a useful conceptual framework for identifying psychosocial risk/protective
factors and directing health initiatives and policies aimed at improving the
psychological health of African American men.
PMID- 29340703
TI - Psychosocial Influences of African Americans Men's Health.
PMID- 29340704
TI - Delayed conception in women with low-urinary iodine concentrations: a population
based prospective cohort study.
AB - STUDY QUESTION: Is iodine deficiency associated with decreased fecundability?
SUMMARY ANSWER: Moderate to severe iodine deficiency is associated with a 46%
decrease in fecundability. WHAT IS KNOWN ALREADY: Iodine deficiency is common in
women of childbearing age but its effect on fecundability has not been
investigated. STUDY DESIGN, SIZE, DURATION: The LIFE Study, a population-based
prospective cohort study, enrolled 501 women who had discontinued contraception
within 2 months to become pregnant between 2005 and 2009. PARTICIPANTS/MATERIALS,
SETTING, METHODS: Women reported on risk factors for infertility by interview
then kept daily journals of relevant information. Women used fertility monitors
to time intercourse relative to ovulation then used home digital pregnancy tests
to identify pregnancies on the day of expected menstruation. Urine samples for
iodine analysis were collected on enrollment. MAIN RESULTS AND THE ROLE OF
CHANCE: Samples were in the deficiency range in 44.3% of participants. The group
whose iodine-creatinine ratios were below 50 MUg/g (moderate to severe
deficiency) had a 46% reduction in fecundity (P = 0.028) compared with the group
whose iodine-creatinine ratios were in the adequate range: adjusted fecundability
odds ratio of becoming pregnant per cycle, 0.54 (95% confidence interval 0.31
0.94). LIMITATIONS, REASONS FOR CAUTION: Iodine concentrations vary within
individuals over time, so the data must be interpreted by group as we have done;
residual confounding is possible. WIDER IMPLICATIONS OF THE FINDINGS: Significant
delays in becoming pregnant occur at iodine concentrations that are common in
women in the USA and parts of Europe. Replicating these findings will be
important to determine whether improving iodine status could be beneficial in
improving fecundability. STUDY FUNDING/COMPETING INTEREST(S): This study was
funded by the Intramural Research Program, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of Health,
USA. Contracts N01-HD-3-3355; N01-HD-3-3356; N01-HD-3-3358 and
HHSN275201100001l/HHSN27500007. None of the authors has any conflict of interest
to declare.
PMID- 29340705
TI - Author Correction: Ouabain attenuates ovalbumin-induced airway inflammation.
AB - In the original publication, author missed to include the financial support from
CAPES/PROCAD-2013. The complete funding text should read as follows.
PMID- 29340706
TI - Prognostic implications of the co-detection of the urokinase plasminogen
activator system and osteopontin in patients with non-small-cell lung cancer
undergoing radiotherapy and correlation with gross tumor volume.
AB - BACKGROUND: The urokinase plasminogen activator system (uPA, uPAR, PAI-1) is
upregulated in cancer and high plasma levels are associated with poor prognosis.
Their interaction with hypoxia-related osteopontin (OPN) which is also
overexpressed in malignant tumors suggests potential clinical relevance. However,
the prognostic role of the uPA system in the radiotherapy (RT) of non-small-cell
lung cancer (NSCLC), particularly in combination with OPN, has not been
investigated so far. METHODS: uPA, uPAR, PAI-1 and OPN plasma levels of 81
patients with locally advanced or metastasized NSCLC were prospectively analyzed
by ELISA before RT and were correlated to clinical patient/tumor data and
prognosis after RT. RESULTS: uPAR plasma levels were higher in M1; uPA and PAI-1
levels were higher in M0 NSCLC patients. uPAR correlated with uPA (p < 0.001)
which also correlated with PAI-1 (p < 0.001). The prognostic impact of OPN plasma
levels in the RT of NSCLC was previously reported by our group. PAI-I plasma
levels significantly impacted overall (OS) and progression-free survival (PFS).
Low PAI-1 levels were associated with a significantly reduced OS and PFS with a
nearly 2-fold increased risk of death (p = 0.029) and tumor progression (p =
0.029). In multivariate analysis, PAI-1 levels remained an independent prognostic
factor for OS and PFS with a 3-fold increased risk of death (p = 0.001). If PAI-1
plasma levels were combined with OPN or tumor volume, we found an additive
prognostic impact on OS and PFS with a 2.5- to 3-fold increased risk of death (p
= 0.01). CONCLUSION: Our results suggest that PAI-1 but not uPA and uPAR might
add prognostic information in patients with advanced NSCLC undergoing RT. High
pretreatment PAI-1 plasma levels were found predominantly in M0-stage patients
and indicate a favorable prognosis as opposed to OPN where high plasma levels are
associated with poor survival and metastasis. In combination, PAI-1 and OPN
levels successfully predicted outcome and additively correlated with prognosis.
These findings support the notion of an antidromic prognostic impact of OPN and
PAI-1 plasma levels in the RT of advanced NSCLC.
PMID- 29340707
TI - VRK1 and AURKB form a complex that cross inhibit their kinase activity and the
phosphorylation of histone H3 in the progression of mitosis.
AB - Regulation of cell division requires the integration of signals implicated in
chromatin reorganization and coordination of its sequential changes in mitosis.
Vaccinia-related kinase 1 (VRK1) and Aurora B (AURKB) are two nuclear kinases
involved in different steps of cell division. We have studied whether there is
any functional connection between these two nuclear kinases, which phosphorylate
histone H3 in Thr3 and Ser10, respectively. VRK1 and AURKB are able to form a
stable protein complex, which represents only a minor subpopulation of each
kinase within the cell and is detected following nocodazole release. Each kinase
is able to inhibit the kinase activity of the other kinase, as well as inhibit
their specific phosphorylation of histone H3. In locations where the two kinases
interact, there is a different pattern of histone modifications, indicating that
there is a local difference in chromatin during mitosis because of the local
complexes formed by these kinases and their asymmetric intracellular
distribution. Depletion of VRK1 downregulates the gene expression of BIRC5
(survivin) that recognizes H3-T3ph, both are dependent on the activity of VRK1,
and is recovered with kinase active murine VRK1, but not with a kinase-dead
protein. The H3-Thr3ph-survivin complex is required for AURB recruitment, and
their loss prevents the localization of ACA and AURKB in centromeres. The cross
inhibition of the kinases at the end of mitosis might facilitate the formation of
daughter cells. A sequential role for VRK1, AURKB, and haspin in the progression
of mitosis is proposed.
PMID- 29340709
TI - [Lichen sclerosus : Symptoms, diagnosis, therapeutic procedures].
AB - Lichen sclerosus is a chronic, inflammatory dermatosis that usually affects the
anogenital area. Early diagnosis and subsequent long-term anti-inflammatory
treatment may reduce symptoms and signs and the risk of a mutilating course and
the development of carcinomas.
PMID- 29340710
TI - Production of plant-derived polyphenols in microorganisms: current state and
perspectives.
AB - Plants synthesize several thousand different polyphenols of which many have the
potential to aid in preventing or treating cancer, cardiovascular, and
neurodegenerative diseases. However, plants usually contain complex polyphenol
mixtures impeding access to individual compounds in larger quantities. In
contrast, functional integration of biosynthetic plant polyphenol pathways into
microorganisms allows for the production of individual polyphenols as chemically
distinct compounds, which can be synthesized in large amounts and can be more
easily isolated. Over the last decade, microbial synthesis of many plant
polyphenols could be achieved, and along the way, many decisive bottlenecks in
the endogenous microbial host metabolism as well as in the heterologous plant
pathways could be identified. In this review, we present recent advancements in
metabolic engineering of microorganisms for the production of plant polyphenols
and discuss how current challenges could be addressed in the future.
PMID- 29340708
TI - Molecular recognition of microbial lipid-based antigens by T cells.
AB - The immune system has evolved to protect hosts from pathogens. T cells represent
a critical component of the immune system by their engagement in host defence
mechanisms against microbial infections. Our knowledge of the molecular
recognition by T cells of pathogen-derived peptidic antigens that are presented
by the major histocompatibility complex glycoproteins is now well established.
However, lipids represent an additional, distinct chemical class of molecules
that when presented by the family of CD1 antigen-presenting molecules can serve
as antigens, and be recognized by specialized subsets of T cells leading to
antigen-specific activation. Over the past decades, numerous CD1-presented self-
and bacterial lipid-based antigens have been isolated and characterized. However,
our understanding at the molecular level of T cell immunity to CD1 molecules
presenting microbial lipid-based antigens is still largely unexplored. Here, we
review the insights and the molecular basis underpinning the recognition of
microbial lipid-based antigens by T cells.
PMID- 29340711
TI - Microbial degradation of triclosan by a novel strain of Dyella sp.
AB - A novel strain capable of degrading triclosan was isolated from the acclimated
activated sludge and identified to be Dyella sp. WW1 based on 16S rDNA analysis.
The effect of initial concentration of triclosan (0.2, 1, 5, and 10 mg/L),
temperature (15, 25, and 35 degrees C), pH (5, 7, and 9), and additional carbon
source on the degradation of triclosan was investigated in a mineral medium. The
results showed that Dyella sp. WW1 can use triclosan as sole carbon source and
degrade it when initial triclosan concentration was in the range of 0.2-10 mg/L.
The optimal condition for Dyella sp. WW1 to degrade triclosan was 15 degrees C
and pH 7. TOC removal efficiency was more than 90%. Dyella sp. WW1 can degrade
3,5-dichloro-4-hydrobenzoic via co-metabolism in the presence of triclosan, but
cannot degrade trimethoprim, sulfamethoxazole, carbamazepine, and diclofenac. In
the presence of glucose, Dyella sp. WW1 firstly utilized glucose to synthesize
the biomass and then degraded triclosan. When triclosan concentration decreased
to an extent (1.2 mg/L in this study), Dyella sp. WW1 started to use glucose
again. The wastewater components did not significantly affect the activity of
Dyella sp. WW1 to degrade triclosan. During the biodegradation process, six
metabolite products were identified. Based on the metabolites, two degradation
pathways were tentatively proposed. In summary, Dyella sp. WW1 could be used for
degrading triclosan in the real wastewater.
PMID- 29340713
TI - Annual Congress of the European Association of Nuclear Medicine Saturday October1
Wednesday October 3, 2006, Athens Greece.
PMID- 29340712
TI - Membrane Position Dependency of the pKa and Conductivity of the Protein Ion
Channel.
AB - The dependency of current-voltage characteristics of the alpha-hemolysin channel
on the channel position within the membrane was studied using Poisson-Nernst
Planck theory of ion conductivity with soft repulsion between mobile ions and
protein atoms (SP-PNP). The presence of the membrane environment also influences
the protonation state of the residues at the boundary of the water-lipid
interface. In this work, we predict that Asp and Lys residues at the protein rim
change their protonation state upon penetration to the lipid environment. Free
energies of protein insertion in the membrane for different penetration depths
were estimated using the Poisson-Boltzmann/solvent-accessible surface area
(PB/SASA) model. The results show that rectification and reversal potentials are
very sensitive to the relative position of channel in the membrane, which in turn
contributes to alternative protonation states of lipid-penetrating ionizable
groups. The prediction of channel position based on the matching of calculated
rectification with experimentally determined rectification is in good agreement
with recent neutron reflection experiments. Based on the results, we conclude
that alpha-hemolysin membrane position is determined by a combination of factors
and not only by the pattern of the surface hydrophobicity as is typically
assumed.
PMID- 29340714
TI - Taxonomical Resolution and Distribution of Bacterioplankton Along the Vertical
Gradient Reveals Pronounced Spatiotemporal Patterns in Contrasted Temperate
Freshwater Lakes.
AB - We examined the relationship between viruses and co-occurring bacterial
communities across spatiotemporal scale in two contrasting freshwater lakes,
namely meromictic Lake Pavin and dimictic Lake Aydat (Central France). Next
generation sequencing of 16S rRNA genes suggested distinct patterns in
bacterioplankton community composition (BCC) between the lakes over depths and
seasons. BCC were generally dominated by members of Actinobacteria,
Proteobacteria, and Bacteroidetes covering about 95% of all sequences. Oxygen
depletion at the bottom waters in Aydat and existence of permanent anoxia in the
monimolimnion of Pavin resulted in the occurrence and dominance of lesser known
members of lake communities such as Methylotenera, Methylobacter, Gallionella,
Sulfurimonas, and Syntrophus in Pavin and Methylotenera and Sulfuritalea in
Aydat. Differences in BCC appeared strongly related to dissolved oxygen
concentration, temperature, viral infection, and virus-to-bacteria ratio. UniFrac
analysis indicated a clear distinction in BCC when the percentage of viral
infected bacterial cells and virus-to-bacteria ratio exceeded a threshold level
of 10% and 5, respectively, suggesting a link between viruses and their potential
bacterial host communities. Our study revealed that in both the lakes, the
prevailing environmental factors across time and space structured and influenced
the adaptation of bacterial communities to specific ecological niches.
PMID- 29340715
TI - Postural control and the relation with cervical sensorimotor control in patients
with idiopathic adult-onset cervical dystonia.
AB - Cervical dystonia (CD) is a movement disorder characterized by involuntary muscle
contractions leading to an abnormal head posture or movements of the neck.
Dysfunctions in somatosensory integration are present and previous data showed
enlarged postural sway in stance. Postural control during quiet sitting and the
correlation with cervical sensorimotor control were investigated. Postural
control during quiet sitting was measured via body sway parameters in 23 patients
with CD, regularly receiving botulinum toxin treatment and compared with 36
healthy controls. Amplitude and velocity of displacements of the center of
pressure (CoP) were measured by two embedded force plates at 1000 Hz. Three
samples of 30 s were recorded with the eyes open and closed. Disease-specific
characteristics were obtained in all patients by the Tsui scale, Cervical
Dystonia Impact Profile (CDIP-58) and Toronto Western Spasmodic Rating Scale
(TWSTRS). Cervical sensorimotor control was assessed with an infrared Vicon
system during a head repositioning task. Body sway amplitude and velocity were
increased in patients with CD compared to healthy controls. CoP displacements
were doubled in patients without head tremor and tripled in patients with a
dystonic head tremor. Impairments in cervical sensorimotor control were
correlated with larger CoP displacements (rs ranged from 0.608 to 0.748).
Postural control is impaired and correlates with dysfunction in cervical
sensorimotor control in patients with CD. Treatment is currently focused on the
cervical area. Further research towards the potential value of postural control
exercises is recommended.
PMID- 29340716
TI - Congenital blindness limits allocentric to egocentric switching ability.
AB - Many everyday spatial activities require the cooperation or switching between
egocentric (subject-to-object) and allocentric (object-to-object) spatial
representations. The literature on blind people has reported that the lack of
vision (congenital blindness) may limit the capacity to represent allocentric
spatial information. However, research has mainly focused on the selective
involvement of egocentric or allocentric representations, not the switching
between them. Here we investigated the effect of visual deprivation on the
ability to switch between spatial frames of reference. To this aim, congenitally
blind (long-term visual deprivation), blindfolded sighted (temporary visual
deprivation) and sighted (full visual availability) participants were compared on
the Ego-Allo switching task. This task assessed the capacity to verbally judge
the relative distances between memorized stimuli in switching (from egocentric-to
allocentric: Ego-Allo; from allocentric-to-egocentric: Allo-Ego) and non
switching (only-egocentric: Ego-Ego; only-allocentric: Allo-Allo) conditions.
Results showed a difficulty in congenitally blind participants when switching
from allocentric to egocentric representations, not when the first anchor point
was egocentric. In line with previous results, a deficit in processing
allocentric representations in non-switching conditions also emerged. These
findings suggest that the allocentric deficit in congenital blindness may
determine a difficulty in simultaneously maintaining and combining different
spatial representations. This deficit alters the capacity to switch between
reference frames specifically when the first anchor point is external and not
body-centered.
PMID- 29340717
TI - Evaluation of left ventricular function after percutaneous recanalization of
chronic coronary occlusions : The role of two-dimensional speckle tracking
echocardiography.
AB - BACKGROUND: This study evaluated the feasibility of using two-dimensional speckle
tracking echocardiography (2D-STE) to monitor left ventricular (LV) and overall
function after percutaneous recanalization. METHODS: LV function after
percutaneous recanalization was monitored by 2D-STE and conventional
echocardiography in 43 patients with coronary chronic total occlusion (CTO) who
underwent primary percutaneous coronary intervention (PCI). Follow-ups were
carried out 1 day as well as 3 and 6 months after CTO-PCI. At each time point, LV
ejection fraction (LVEF) was examined by echocardiography, and LV global
longitudinal strain (GLS) was measured by 2D-STE. RESULTS: It was found that the
global longitudinal strain assessed with 2D-STE was improved as early as 1 day
after CTO-PCI, whereas LVEF tended to improve up to 3 and 6 months after CTO-PCI.
CONCLUSION: PCI can effectively improve LV function in patients with CTO. 2D-STE
is a superior technique for objectively quantifying the functional change
earlier.
PMID- 29340718
TI - Drug treatment of heart failure in the elderly.
AB - The prevalence of heart failure increases with age. Changes in the age
distribution and growing life expectancy will lead to a further rise. However,
data concerning drug treatment of heart failure especially in the elderly are
scarce. Subgroup analyses of the heart failure trials suggest that drug therapy
in older patients should follow the recommendations in the current guidelines. In
doing so, several common comorbidities in these patients (e. g., impaired renal
function) have to be considered and may have an influence on the therapy (e. g.,
drug dose, choice of active pharmaceutical ingredient, etc.). Especially in old,
multimorbid patients, possible interaction of drugs might play a substantial
role. In many cases the main goal of the therapy, especially in the very elderly,
is to improve symptoms and quality of life.
PMID- 29340719
TI - Treatment with 48-mm everolimus-eluting stents : Procedural safety and 12-month
patient outcome.
AB - BACKGROUND: Lesion length is a major predictor of adverse outcomes after
percutaneous coronary intervention. Long lesions often require multiple stents
with variable overlap, which increases the probability of geographical miss and
the incidence of mechanical complications, such as side-branch occlusion,
restenosis, and stent thrombosis. These pitfalls may be avoided by use of an
ultra-long device. METHODS: We retrospectively assessed the performance of the 48
mm Xience Xpedition everolimus-eluting stent (EES) at our institution. RESULTS: A
total of 123 patients (mean age: 60.94 years, n = 93 [76%] male) with 129 lesions
were identified. Lesions (n = 69, 53.5%) were located in the left anterior
descending artery, the right coronary artery (n = 47, 36.4%), and the circumflex
artery (n = 8, 6.2%); 83 lesions involved a major side branch. The majority were
treated with a provisional single-stent strategy. Other characteristics included
significant tortuosity in 15 lesions (11.6%) and moderate-to-heavy calcification
in 46 lesions (35.7%). In all cases, balloon pre-dilatation was performed before
stent insertion. Successful delivery and deployment of the 48-mm EES device was
achieved in 100% of the patients. The mean number of stents per lesion was 1.4,
while the mean total stent length was 58 +/- 17.3 mm and mean stent diameter,
3.00 +/- 0.67 mm. The procedural success rate was 99.2%. The 30-day major cardiac
adverse event (MACE) rate was 0.8%, while the 12-month MACE was 3.3%. CONCLUSION:
The Xience 48-mm EES device appears to be safe and efficacious with a low
clinical event rate at the 12-month follow-up. Where feasible, this would support
the use of the ultra-long 48-mm platform in lieu of multiple overlapping shorter
devices.
PMID- 29340720
TI - Correction to: Polymyxin B-immobilized hemoperfusion and mortality in critically
ill adult patients with sepsis/septic shock: a systematic review with meta
analysis and trial sequential analysis.
AB - Owing to an oversight by the authors, Figure 2 in this article was not the
version intended for publication. The correct Figure 2, reproduced here, features
footnote symbols and Figure 2b includes three studies as described in the main
text.
PMID- 29340721
TI - Geochemical Assessment of Fluoride Pollution in Groundwater of Tribal Region in
India.
AB - This study assessed the fluoride (F-) pollution in groundwater samples (n = 170)
of tribal regions around Bailadila Iron Ore Mines [BIOM] Complex of Dantewada
District, India. Weathering of carbonate and silicate clays were important
geogenic sources of dissolved ions. A Piper diagram showed a Ca-HCO3 water type,
with positive chloro-alkaline indices illustrating the occurrence of direct base
exchange reactions. The F- concentrations varied from 0.08 to 1.95 mg L-1 with a
mean value of 0.9 +/- 0.3 mg L-1. Only two groundwater samples showed F-
concentrations > 1.5 mg L-1, the drinking water guideline established by the
World Health Organization (WHO) and Bureau of Indian Standards (BIS). Factor
analysis showed high loadings of HCO3- and F-, indicating alkaline conditions,
favoring the dissolution of F- in the groundwater. The K fluor value is less than
10-10.6, indicating that the dissociation of fluorite is very slow. As a result,
groundwater locations were under-saturated with respect to fluorite.
PMID- 29340722
TI - New frontiers and cutting edge applications in ultra high performance liquid
chromatography through latest generation superficially porous particles with
particular emphasis to the field of chiral separations.
AB - About ten years after their introduction to the market (happened in 2006), the so
called second generation superficially porous particles (SPPs) have undoubtedly
become the benchmark as well as, very often, the preferred choice for many
applications in liquid chromatography (LC), when high efficiency and fast
separations are required. This trend has interested practically all kinds of
separations, with the only exception of chiral chromatography (at least so far).
The technology of production of base SPPs is advanced, relatively simple and
widely available. The deep investigation of mass transfer mechanisms under
reversed-phase (RP) and normal-phase (NP) conditions for achiral separations has
shown the advantages in the use of these particles over their fully porous
counterparts. In addition, it has been demonstrated that SPPs are extremely
suitable for the preparation of efficient packed beds through slurry packing
techniques. However, the research in this field is in continual evolution. In
this article, some of the most advanced concepts and modern applications based on
the use of SPPs, embracing in particular ultrafast chiral chromatography and the
design of SPPs with engineered pore structures or very reduced particle diameter,
are revised. We describe modern trends in these fields and focus on those aspect
where further innovation and research will be required. Graphical Abstract Word
cloud of cutting edge applications of superficially porous particles in liquid
chromatography.
PMID- 29340723
TI - Veno-Venous Extracorporeal Membrane Oxygenation (VV ECMO) for Acute Respiratory
Failure Following Injury: Outcomes in a High-Volume Adult Trauma Center with a
Dedicated Unit for VV ECMO.
AB - INTRODUCTION: The use of veno-venous extracorporeal membrane oxygenation (VV
ECMO) has increased over the past decade. The purpose of this study was to
evaluate outcomes in adult trauma patients requiring VV ECMO. METHODS: Data were
collected on adult trauma patients admitted between January 1, 2015, and November
1, 2016. Demographics, injury-specific data, ECMO data, and survival to discharge
were recorded. Medians [interquartile range (IQR)] were reported. A p value
<=0.05 was considered statistically significant. RESULTS: Eighteen patients
required VV ECMO during the study period. Median age was 28.5 years (IQR 24-43).
Median injury severity score (ISS) was 27 (IQR 21-41); median PaO2/FiO2 (P/F)
prior to ECMO cannulation was 61 (IQR 50-70). Median time from injury to
cannulation was 3 (IQR 0-6) days. Median duration of ECMO was 266 (IQR 177-379)
hours. Survival to discharge was 78%. Survivors had a significantly higher ISS (p
= 0.03), longer intensive care unit length of stay (ICU LOS) (p < 0.0004),
hospital LOS (p < 0.000004), and time on the ventilator (p < 0.0003). Median time
of injury to cannulation was significantly longer in patients who survived to
discharge (p = 0.01). There was no difference in P/F ratio prior to cannulation
(p = ns). CONCLUSION: We have demonstrated improved outcome of patients requiring
VV ECMO following injury compared to historical data. Although shorter time from
injury to cannulation for VV ECMO was associated with death, select patients who
meet criteria for VV ECMO early following injury should be referred/transferred
to a tertiary care facility that specializes in trauma and ECMO care.
PMID- 29340724
TI - The Role of Surgery in Treating Resectable Limited Disease of Esophageal
Neuroendocrine Carcinoma.
AB - BACKGROUND: Esophageal neuroendocrine carcinoma (NEC) is a rare malignant tumor.
The role of surgery in resectable limited disease of esophageal NEC remains
unclear. How to select a specific group of limited disease of esophageal NEC who
might benefit from surgery remains to be answered. METHODS: Patients undergoing
esophagectomy for resectable limited disease of esophageal NEC in our department
from January 2007 to June 2015 were analyzed. TNM staging system was applied to
describe those patients, and according to their different long-term prognosis
after surgery, those patients were subgrouped into surgery response limited
disease (SRLD) group and surgery non-response limited disease (SNRLD) group. Both
univariate and multivariate analyses were applied to identify potential
prognostic factors. RESULTS: A total of 72 patients with resectable limited
disease of esophageal NEC were identified for analysis. The median survival time
of those patients was 21.5 months. There was no significant survival differences
among stage I, stage IIA, and stage IIB patients, but all these patients had
significantly longer survival than stage III patients. Therefore, stage I, stage
IIA, and stage IIB patients were aggregated together as SRLD group, and stage III
patients were aggregated as SNRLD group. SRLD patients obtained significantly
longer survival than SNRLD patients in both univariate analysis and multivariate
analysis. Moreover, adjuvant therapy could significantly benefit SRLD patients (P
= 0.004) but could not benefit SNRLD patients (P = 0.136). CONCLUSIONS: Different
responses to surgery existed in resectable limited disease of esophageal NEC
indicating the need of further subgrouping for those patients. The resectable
limited disease of esophageal NEC could be further subgrouped into SRLD group and
SNRLD group according to the TNM staging system.
PMID- 29340725
TI - Decision-Making in Management of the Complex Trauma Patient: Changing the Mindset
of the non-trauma Surgeon.
AB - BACKGROUND: European surgeons are frequently subspecialized and trained primarily
in elective surgical techniques. As trauma leaders, they may occasionally have to
deal with complex polytrauma, advanced management techniques, differing
priorities, and the need for multidisciplinary care. There is a lack of
expertise, experience, and a low trauma volume, as well as a lack of research,
with limited support as to the decision-making and teaching challenges present.
We studied what experienced trauma experts describe as the challenges that are
specific to the advanced surgical decision-making required, whether civilian,
humanitarian, or military. METHODS: Design-based research using combined methods
including interviews, reviews of authentic trauma cases, and video-recorded
resuscitations performed at a high-volume civilian academic trauma center.
RESULTS: Several educational dilemmas were identified: (1) thinking
physiologically, (2) the application of damage control resuscitation and surgery,
(3) differing priorities and time management, (4) impact of environment, (5)
managing limited resources, (6) lack of general surgical skills, (7) different
cultural behavior, and (8) ethical issues. CONCLUSION: The challenges presented,
and the educational domains identified, constitute a basis for improved
development of education and training in complex surgical decision-making. This
study contributes new knowledge about the mindset required for decision-making in
patients with complex multisystem trauma and competing priorities of care. This
is, especially important in countries having a low intensity of trauma in both
military and civilian environments, and consequential limited skills, and lack of
expertise. Guidelines focused on the same decision-making process, using virtual
patients and blended learning, can be developed.
PMID- 29340726
TI - Prognostic Prediction Models for Resection of Large Hepatocellular Carcinoma: A
Korean Multicenter Study.
AB - BACKGROUND: We developed a prognostic prediction model (PPM) using 4 factors for
hepatic resection (HR) of large hepatic cellular carcinoma (HCC). Multiplication
of alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin, and tumor volume (TV)
(ADV score) is a surrogate marker for post-resection prognosis. This study
intended to validate the predictive power of 4-factor PPM and to develop new ADV
score-based PPM. METHODS: A total of 526 patients who underwent HR for solitary
HCC >= 8 cm were selected from 9 Korean institutions between 2008 and 2014.
RESULTS: Median tumor diameter and TV were 11.0 cm and 398 mL, respectively.
Tumor recurrence and patient survival rates were 53.0 and 78.4% at 1 year and
70.2 and 49.3% at 5 years, respectively. Independent risk factors for both tumor
recurrence and patient survival included AFP >= 100 ng/mL, hypermetabolic FDG
positron emission tomography (PET), microvascular invasion and satellite nodules,
which comprised 4 factors of the PPM. Five subgroups based on the number of
involved risk factors exhibited significant differences in tumor recurrence and
patient survival. ADV score cutoff was set at 7log (ADV7log) after cluster
prognostic analysis. Patient grouping according to combination of ADV7log and FDG
PET findings (ADV7log-PET) exhibited significant differences in tumor recurrence
and patient survival, comparable to those of the 4-factor PPM. CONCLUSIONS: Two
PPMs using 4 risk factors and ADV7log-PET could reliably predict the risk of
early HCC recurrence and long-term survival outcomes in patients who underwent HR
for large HCC. We believe that these PPMs can guide surgical treatment for large
HCCs from preoperative HR planning to post-resection follow-up.
PMID- 29340727
TI - Parastomal Hernia Repair with a 3D Funnel Intraperitoneal Mesh Device and Same
Sided Stoma Relocation: Results of 56 Cases: Reply.
PMID- 29340729
TI - Pulmonary Valve Morphology in Patients with Bicuspid Aortic Valves.
AB - The aortic and pulmonary valve share a common developmental origin from the
embryonic arterial trunk. Bicuspid aortic valve is the most common congenital
anomaly and can occur isolated as well as in association with other congenital
heart disease (CHD). Data on pulmonary valve morphology in these cases are
scarce. In this study, we aimed to determine pulmonary valve morphology in hearts
with BAV associated with CHD. In 83 post-mortem heart specimens with BAV and
associated CHD, pulmonary valve morphology was studied and related to BAV
morphology. In 14/83 (17%) hearts, the pulmonary valve was affected, bicuspid in
8/83 (10%), dome-shaped in 3/83 (4%) and atretic in 3/83 (4%). In specimens with
a bicuspid pulmonary valve, 5/8 (63%) had a strictly bicuspid aortic valve
(without raphe), 2/3 hearts (67%) with dome-shaped pulmonary valves and 2/3
hearts (67%) with atretic pulmonary valves had BAV without raphe. Six out of
eight (75%) specimens with a bicuspid pulmonary valve had a perimembranous
ventricular septal defect (VSD). 4/8 (50%) specimens with a bicuspid pulmonary
valve were associated with chromosomal abnormalities: 3 (38%) had trisomy 18 and
1 (13%) had trisomy 13. In BAV with associated CHD, abnormal pulmonary valve
morphology was observed in 17% of the hearts. The majority of hearts with
abnormal pulmonary valve morphology had a Type B bicuspid aortic valve (without
raphe). Bilateral semilunar valvular disease is associated with Type B BAVs and
in many cases related to chromosomal abnormalities. As this study was performed
in post-mortem specimens with high frequency of associated CHD, caution is
warranted with application of these results to the general BAV population.
PMID- 29340728
TI - Indocyanine Green Retention Rates at 15 min Predicted Hepatic Decompensation in a
Western Population.
AB - BACKGROUND: ICGR15 is widely used in Asia to evaluate the liver reserve before
hepatectomy, but not in Western countries where patients are selected using the
MELD score and/or platelet count. Postoperative liver failure is rare nowadays,
but hepatic decompensation (HD), defined by 3-month postoperative ascites,
impairs quality of life and survival. The aim of this study was to evaluate the
relevance of indocyanine green retention rate at 15 min (ICGR15) before liver
resection in Western countries, in order to predict HD. METHODS: This
prospectively designed study included consecutive adult patients undergoing
hepatectomy for hepatocellular carcinoma (HCC) and intrahepatic
cholangiocarcinoma (ICC) in three French HPB centres. RESULTS: Between 2012 and
2014, 147 patients were included (80% of HCC and 20% of ICC). The Child-Pugh
status was grade A for all patients. In the overall population and in F3/F4
patients (n = 83), ICGR15 (P = 0.02) and platelet counts (P = 0.02) were
predictive of HD under multivariate analysis. Among F3/F4 patients undergoing
minor hepatectomy with preoperative ICGR15 > 15%, the rate of HD was 36%. In the
overall population, ICGR15 was predictive of HD (P = 0.02) and postoperative
ascites (P = 0.03). The ROC curve identified a cut-off point of 15% as being
associated with increased HD, with good accuracy for ICGR15 in the study
population (AUROC 0.73), mainly before minor hepatectomy (AUROC 0.79).
CONCLUSIONS: In patients with HCC and ICC selected using the MELD score and
platelet rate, an ICGR15 > 15% is a relevant, non-invasive and clearly accurate
method to predict HD specially before minor hepatectomy.
PMID- 29340730
TI - Age-Dependent Association Between Pre-transplant Blood Transfusion and Outcomes
of Pediatric Heart Transplantation.
AB - Avoidance of red blood cell (RBC) transfusions in patients awaiting heart
transplantation (HTx) has been suggested to minimize the risk of
allosensitization. Although recent studies have suggested that an immature immune
system in younger HTx recipients may reduce risks associated with RBC
transfusion, the role of age in moderating the influence of transfusion on HTx
outcomes remains unclear. We used available data from a national transplant
registry to explore whether the association between pre-transplant transfusions
and outcomes of pediatric HTx varies by patient age. De-identified data were
obtained from the United Network for Organ Sharing registry, including first-time
recipients of isolated HTx performed at age 0-17 years in 1995-2015. The primary
exposure was receiving blood transfusions within 2 weeks prior to HTx. Patient
survival after HTx was evaluated using multivariable Cox proportional hazards,
where age at transplant was interacted with exposure to pre-transplant
transfusion. Age-specific hazard ratios (HRs) of pre-transplant transfusion were
plotted across ages at transplant. There were 4883 patients meeting inclusion
criteria, of whom 1258 died during follow-up (mean follow-up duration 6 +/- 5
years). Patients receiving pre-transplant transfusions were distinguished by
younger age, higher prevalence of prior cardiac surgery, greater likelihood of
being in the intensive care unit, and greater use of left ventricular assist
device bridge to transplant. In multivariable analysis, pre-transplant
transfusions were associated with increased mortality hazard among infants < 1
year of age (HR = 1.46; 95% CI 1.23, 1.74; p < 0.001). For each additional year
of age, the excess hazard associated with pre-transplant transfusions decreased
by 3% (interaction HR = 0.97; 95% CI 0.98, 0.99; p = 0.003). By age 8, the
association between pre-transplant transfusions and post-transplant mortality was
no longer statistically significant (HR = 1.15; 95% CI 0.99, 1.32; p = 0.060).
Pre-transplant transfusions were associated with increased mortality hazard only
among younger children (age < 8 years) undergoing HTx. These data support the
current practices of transfusion avoidance prior to HTx, particularly in younger
patients.
PMID- 29340732
TI - [Electronic decision support to promote medication safety].
AB - Because of its inherent complexity, it is a considerable challenge to tailor drug
treatment to a prevalent disease and its subgroups, which are increasingly
defined by genomic variability (personalized medicine) and require consideration
of context information such as co-morbidity, co-medication, patient preferences,
and the specific characteristics of the healthcare sector. Thus, optimum
treatment decisions might not be taken intuitively any longer, because decisions
must be made both rapidly and increasingly based on analyses of complex relations
of numerous variables that exceed the processing performance of a human brain.
Hence, computer support is indispensable to ensure error-free high-performance
medicine. A key step in computer-supported medication safety is to implement a
computerized physician order entry (CPOE) system that compiles a patient's
medication in a structured and coded format enabling the link to clinical
decision support (CDS) systems. Implementing a CPOE is hence a strategic step for
a hospital, which is crucial to exhaustingly and consistently prevent medication
errors. Thereby, the best performance of a CPOE is achieved if it is deeply
integrated into an electronic patient record thus enabling access to relevant
patient information, which again has to be structured to allow processing. To
efficiently support drug treatment, CDS systems must fulfill high-quality
standards with regard to underlying data, integration, and user-interaction to
ensure that they support but do not impede the provision of care.
PMID- 29340731
TI - Sensitive Cardiac Troponins: Could They Be New Biomarkers in Pediatric Pulmonary
Hypertension Due to Congenital Heart Disease?
AB - To analyze the role of sensitive cardiac troponin I (scTnI) and high-sensitive
troponin T (hscTnT) in the determination of myocardial injury caused by volume
and pressure load due to pulmonary hypertension (PH) and to investigate if these
markers may be useful in the management of PH in childhood. Twenty-eight patients
with congenital heart disease (CHD) with left to right shunt and PH, 29 patients
with CHD with left to right shunt but without PH, and 18 healthy children, in
total 75 individuals, were included in the study. All cases were aged between 4
and 36 months. Echocardiographic evaluation was performed in all cases, and
invasive hemodynamic investigation was performed in 33 cases. Blood samples were
obtained from all cases, for the measurement of brain natriuretic peptide (BNP),
pro-brain natriuretic peptide (pro-BNP), sensitive cardiac troponin I (scTnI),
and high-sensitive troponin T (hscTnT) levels. The mean BNP, pro-BNP, scTnI, and
hsTnT levels were statistically significantly higher in patients with PH than in
the patients without PH (p < 0.001). A statistically significant positive
correlation was determined between pulmonary artery systolic pressure and scTnI
and hscTnT levels (r = 0.34 p = 0.01, r = 0.46 p < 0.001, respectively) levels.
Pulmonary hypertension determined in congenital heart diseases triggers
myocardial damage independently of increased volume or pressure load and
resistance, occurring by disrupting the perfusion via increasing ventricular wall
tension and the myocardial oxygen requirement. Serum scTnI and hscTnT levels may
be helpful markers to determine the damage associated with PH in childhood.
PMID- 29340737
TI - [Rhinoplasty-state of the art].
PMID- 29340736
TI - Risk factors for early infection following hemiarthroplasty in elderly patients
with a femoral neck fracture.
AB - PURPOSE: Periprosthetic joint infections (PJI) after hemiarthroplasty for
geriatric femoral neck fractures are a devastating complication that results in
serious morbidity and increased mortality. Identifying risk factors associated
with early infection after HA for hip fractures may offer an opportunity to
address and prevent this complication in many patients. The aim of this study was
to evaluate preoperative risk factors for early PJI after HA in hip fracture
patients. METHODS: From January 2010 to December 2015, 312 femoral neck fractures
(AO/OTA 31-B) in 305 patients were included in this single-center, retrospective
study. PJI was defined according to the Centers for Disease Control (CDC)
definition of deep incisional surgical site infection. Early infection referred
to a postoperative period of 4 weeks. Binary univariable and multivariable
regression analysis with backward elimination was applied to identify predictors
of PJI. RESULTS: Median age of all patients was 83.0 (IQR 76-89) years. We
identified 16 (5.1%) early PJI which all required surgical revision. Median
length of in-hospital stay (LOS) was 20.0 (IQR 10-36) days after PJI compared to
10.0 (8-15) days without deep wound infection. In-hospital mortality was 30.8 vs.
6.6%, respectively. Preoperative CRP levels (OR 1.009; 95% CI 1.002-1.018; p =
0.044), higher BMI (OR 1.092; 95% CI 1.002-1.189; p = 0.044) and prolonged
surgery time (OR 1.013; 95% CI 1.000-1.025; p = 0.041) were independent risk
factors for PJI. Excluding infection following major revision due to mechanical
complications identified preoperative CRP levels (OR 1.012; 95% CI 1.003-1.021; p
= 0.007) and chronic glucocorticoid therapy (OR 6.314; 95% CI 1.223-32.587; p =
0.028) as risk factors, a clear trend was seen for higher BMI (OR 1.114; 95% CI
1.000-1.242; p = 0.051). A cut-off value at CRP levels >= 14 mg/l demonstrated a
sensitivity of 69% and a specificity of 70% with a fair accuracy (AUC 0.707).
CONCLUSION: Preoperative serum CRP levels, higher BMI and prolonged surgery time
are independent predictors of early PJI. Excluding PJI secondary to major
revision surgery revealed chronic glucocorticoid use as a risk factor apart from
preoperative CRP levels.
PMID- 29340733
TI - Population pharmacokinetics of lamotrigine co-administered with valproic acid in
Chinese epileptic children using nonlinear mixed effects modeling.
AB - PURPOSE: The aims of this study were to develop a population pharmacokinetic
(PPK) model of lamotrigine (LTG) in Chinese epileptic children by using nonlinear
mixed effects modeling (NONMEM) and to investigate the effects of valproic acid
(VPA) and genetic polymorphisms of the major metabolizing enzymes (UGT1A4,
UGT2B7) on the pharmacokinetics of LTG. METHODS: A total of 182 epileptic
children who were treated with LTG as monotherapy or as part of combination
therapy were included in this study as the model group, and 61 patients were
included as the validation group. The steady-state serum trough concentrations of
LTG and VPA were determined using a high-performance liquid chromatography method
and fluorescence polarization immunoassay, respectively. Patients were genotyped
for three single nucleotide polymorphisms (UGT1A4 142T>G, UGT2B7 -161C>T, and
UGT2B7 802C>T). PPK analysis was performed with NONMEM using first-order
absorption and elimination. Bootstrap, normalized prediction distribution errors
and external evaluations were performed to determine the stability and predictive
performance of the model. RESULTS: For the final model, the oral clearance (CL/F)
of LTG was estimated to be 0.705 L/h with inter-individual variability (IIV) of
21.3%. The estimates generated by NONMEM indicated that the LTG CL/F was
significantly influenced by patient body weight (increased with an exponent of
0.574) and VPA concentration (decreased with linearity of 0.273 with co
administration). However, no significant effects of UGT1A4 or UGT2B7
polymorphisms on LTG CL/F were noted in this population of Chinese children.
CONCLUSION: This study confirms the interaction of LTG with VPA, which likely
depends on VPA concentration. The LTG PPK model developed in this study could be
useful for individualizing LTG dosage regimens in pediatric patients receiving
combination therapy, especially therapy that includes VPA.
PMID- 29340738
TI - ?
PMID- 29340739
TI - ?
PMID- 29340740
TI - [Paraneoplastic syndromes in rheumatology].
AB - Malignancies can present as inflammatory rheumatic diseases. These rheumatic
paraneoplastic syndromes are rare, but characteristic in their pattern. This
article focuses on epidemiology, clinical and diagnostic features as well as
treatment of paraneoplasic rheumatic diseases such as paraneoplastic arthritides,
vasculitides, myositis and hypertrophic osteoarthropathy. The knowledge of their
clinical patterns is of utmost importance for early diagnosis and prognosis of
yet undiagnosed malignancies.
PMID- 29340741
TI - [Platelet inhibition in patients with coronary, cerebral and peripheral
macroangiopathy : What, when and how long?]
AB - BACKGROUND: Inhibition of platelet aggregation can reduce the rate of vascular
events in patients with coronary artery disease, carotid artery stenosis and
symptomatic peripheral arterial disease. The choice of platelet inhibitors in
monotherapy and combination therapy as well as the duration of dual platelet
inhibition depend on the clinical situation and individual patient
characteristics. GOAL: The present review summarizes the latest data from
clinical trials and recommendations regarding platelet inhibition in coronary,
cerebral and peripheral arterial disease. DATA: A large number of randomized
trials on platelet inhibition in different clinical situations have been
performed, allowing evidence-based recommendations on the choice of drugs and
duration of treatment. Moreover, new guidelines of European professional
societies on platelet inhibition in patients with coronary, cerebral and
peripheral arterial disease have been recently published. CONCLUSION: Based on
latest randomized trials and major society guidelines, a number of
recommendations on platelet inhibition in stable coronary artery disease, after
stent implantation, after acute coronary syndromes and in cerebral and peripheral
arterial disease can be made.
PMID- 29340742
TI - [Wilson disease].
AB - Wilson disease is a rare hereditary disorder of copper metabolism. The genetic
defect is caused by various mutations in the copper-transporting enzyme ATP7B,
located mainly in the liver and brain. Clinical symptoms are highly variable,
with any combination of hepatic and/or neurological or psychiatric
manifestations. The age of onset varies from early childhood to young adults and
can even be manifested in later ages. The clinical diagnosis is based on a
combination of clinical, biochemical and molecular markers. Treatment using
chelating agents and zinc salts is effective when started early or even better at
presymptomatic stages of the disease.
PMID- 29340743
TI - Recent Trends and Advances in Cancer-Induced Bone Disease.
PMID- 29340744
TI - Highlight report: 'Big data in the 3R's: outlook and recommendations', a
roundtable summary.
PMID- 29340745
TI - A 6-week warm-up injury prevention programme results in minimal biomechanical
changes during jump landings: a randomized controlled trial.
AB - PURPOSE: To examine the extent to which an ACL injury prevention programme
modifies lower extremity biomechanics during single- and double-leg landing tasks
in both the sagittal and frontal plane. It was hypothesized that the training
programme would elicit improvements in lower extremity biomechanics, but that
these improvements would be greater during a double-leg sagittal plane landing
task than tasks performed on a single leg or in the frontal plane. METHODS:
Ninety-seven competitive multi-directional sport athletes that competed at the
middle- or high-school level were cluster randomized into intervention (n = 48,
age = 15.4 +/- 1.0 years, height = 1.7 +/- 0.07 m, mass = 59.9 +/- 11.0 kg) and
control (n = 49, age = 15.7 +/- 1.6 years, height = 1.7 +/- 0.06 m, mass = 60.4
+/- 7.7 kg) groups. The intervention group participated in an established 6-week
warm-up-based ACL injury prevention programme. Three-dimensional biomechanical
analyses of a double- (SAG-DL) and single-leg (SAG-SL) sagittal, and double-
(FRONT-DL) and single-leg (FRONT-SL) frontal plane jump landing tasks were tested
before and after the intervention. Peak angles, excursions, and external joint
moments were analysed for group differences using 2 (group) * 4 (task) repeated
measures MANOVA models of delta scores (post-pre-test value) (alpha < 0.05).
RESULTS: Relative to the control group, no significant biomechanical changes were
identified in the intervention group for any of the tasks (n.s.). However, a
group by task interaction was identified for knee abduction (lambda = 0.80, p =
0.02), such that participants in the intervention group showed relative decreases
in knee abduction moments during the SAG-DL compared to the SAG-SL (p = 0.005; d
= 0.45, CI = 0.04-0.85) task. CONCLUSION: A 6-week warm-up-based ACL injury
prevention programme resulted in no significant biomechanical changes during a
variety of multi-directional jump landings. Clinically, future prevention
programmes should provide a greater training stimulus (intensity, volume), more
specificity to tasks associated with the mechanism of ACL injury (single-leg, non
sagittal plane jump landings), and longer programme duration (> 6 weeks) to
elicit meaningful biomechanical changes. LEVEL OF EVIDENCE: I.
PMID- 29340746
TI - Similar clinical outcomes following collagen or polyurethane meniscal scaffold
implantation: a systematic review.
AB - PURPOSE: The purpose of this systematic review is to evaluate the current
literature in an effort to assess specific clinical outcomes following meniscal
scaffold implantation using the two available scaffolds: Collagen Meniscal
Implant (CMI) and the Actifit polyurethane meniscal scaffold. METHODS: A
systematic review was performed by searching PubMed, Embase, and Cochrane Library
to find studies evaluating clinical outcomes of patients undergoing meniscal
scaffold implantation. Search terms used were "meniscus", "meniscal", "scaffold",
and "implant". Studies were evaluated based on scaffold type, treatment failure
rates, patient-reported outcome scores, concomitant procedures, and radiological
findings. Radiological findings were recorded using the Genovese scale to assess
morphology and signal intensity and the Yulish score to assess articular
cartilage. RESULTS: Nineteen studies (1 level I, 1 level II, 17 level IV
evidence) were identified that met inclusion criteria, including a total of 658
patients (347 Actifit, 311 CMI). The overall average follow-up was 45 months.
Treatment failure occurred in 9.9% of patients receiving the Actifit scaffold at
a mean follow-up of 40 months and 6.7% of patients receiving CMI at a mean follow
up of 44 months (n.s.). However, the rate of failure ranged from 0 to 31.8%
amongst the included studies with a variable definition of failure. Additionally,
overlapping patients and presence of concomitant surgeries such as anterior
cruciate ligament reconstruction (ACLR) and high tibial osteotomy (HTO) may have
a significant influence on these results. Outcomes for the Visual Analog Scale
(VAS) for pain, Lysholm knee score, and Tegner activity score improved from
preoperatively to latest follow-up in both groups, while the Knee Injury and
Osteoarthritis Outcome Score and International Knee Documentation Committee
scores improved from preoperatively to latest follow-up for Actifit scaffold
patients. Overall, patients receiving CMI scaffolds had higher grades for
Genovese morphology and signal intensity when compared to Actifit scaffold
patients. CONCLUSION: Patients undergoing meniscal scaffold implantation with
either CMI or Actifit scaffold can both be expected to experience improvement in
clinical outcomes when used in association with concomitant procedures such as
ACLR and HTO. LEVEL OF EVIDENCE: IV, systematic review.
PMID- 29340747
TI - The role of muscle function after anterior cruciate ligament rupture and
treatment.
PMID- 29340749
TI - In Pursuit of Effective Volume Reduction and Enhanced Aesthetics for Treatment of
Gigantomastia Using Superior Dermoglandular Pedicle.
AB - BACKGROUND: Gigantomastia is defined as extreme hypertrophy of the female breast.
It is a disabling condition that presents unique challenges to plastic surgeons.
Initial breast volume is an important factor affecting the success of the
reduction. Usually, it is difficult to achieve small-sized breasts, and long-term
results are often unsatisfactory, resulting in complications such as "bottoming
out" deformities. METHODS: This paper presents a case series involving 40
patients (mean age 44.2 +/- 12.5) with gigantomastia. Reductions were performed
by superior nipple-areola complex pedicle with or without liposuction. Total
resection weight ranged from 2050 to 5398 g (mean 3066 +/- 944.2). Generally, the
literature emphasizes the unreliability of the long superior pedicle when used to
reduce the size of very large breasts. The technical steps for this procedure
have been clearly described, and ways in which to overcome technical difficulties
and attain effective volume reduction with minimal complications were presented.
RESULTS: The technique described here is applicable to all gigantomastia cases;
even very large, pendulous breasts could be effectively reduced. Physical
symptoms rapidly improved during the early postoperative period, patients'
aesthetic satisfaction scores were high (4.6/5), and none of the patients
complained of flat breasts. The rate of partial areola necrosis was 5%, and the
rate of complete areola necrosis was 2.5%. These rates are comparable to those in
the literature. CONCLUSION: Using the technique described above, superior pedicle
can be applied to all gigantomastia cases and enhanced aesthetic results can be
obtained with minimal complications. 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- 29340750
TI - A Pilot Study Evaluating the Efficacy and Safety of ARTISS Human Fibrin Sealant
in External Rhinoplasty.
AB - BACKGROUND: Fibrin sealant application in rhytidectomy has previously
demonstrated a reduction in adverse events and drainage volume. Fibrin sealant
offers multiple potential benefits including decreasing downtime, reducing
complication rates, and improving patient satisfaction. In this study, we
evaluated the efficacy and safety of ARTISS [fibrin sealant (human)] in external
rhinoplasty. METHODS: Nine healthy participants between the ages of 18 and 50
seeking external rhinoplasty completed this study. All subjects were randomized
into control and treatment groups and then underwent external rhinoplasty, with
only the treatment group receiving ARTISS [fibrin sealant (Human)] during
surgery. Photographs were taken before surgery and 1 day, 1 week, 1 month, 3
months and 6 months after surgery and used in a blinded assessment of recovery
time and esthetic improvement with ecchymosis and satisfaction scales. Subject
recovery time, downtime, and self-esteem were evaluated at 1 day, 1 week, 1 month
and 6 months after surgery. Recovery time was determined by live assessment of
edema and ecchymosis using categorical scales. Subject downtime was assessed
through a 30-day patient diary and a downtime questionnaire. Subject self-esteem
was evaluated with the Heatherton & Polivy State Self-Esteem Scale. The degree of
technical ease with the product was determined by the treating investigator with
a 10-cm Visual Analog Scale. RESULTS: Patients treated with ARTISS intra
operatively reported significantly higher self-esteem 1 month and 6 months
following external rhinoplasty. The ARTISS EasysprayTM Spray Set was rated as
technically easy to administer. CONCLUSION: The use of ARTISS fibrin sealant in
external rhinoplasties is a safe and easy method and may enhance patient self
esteem. Larger studies are warranted to either verify or challenge the validity
of our findings. LEVEL OF EVIDENCE IV: This journal requires that authors assign
a level of evidence to each article. For a full description of these Evidence
Based Medicine ratings, please refer to the Table of Contents or the online
Instructions to Authors www.springer.com/00266 .
PMID- 29340748
TI - Lack of level I evidence on how to prevent infection after elective shoulder
surgery.
AB - PURPOSE: Infection is a concern after all orthopedic procedures, including
shoulder surgery. This systematic review of literature aimed to determine risk
factors for infection as well as the availability and effectiveness of measures
utilized to prevent infection after elective shoulder surgery. METHODS: An
electronic database search was performed using MEDLINE (1950-October 2017),
EMBASE (1980-October 2017), CINAHL (1982-October 2017), and the Cochrane database
to identify studies reporting a risk factor or preventive measure for infection
after shoulder surgery. RESULTS: Fifty-one studies were eligible for inclusion.
Risk factors identified for infection were male sex, the presence of hair,
receiving an intra-articular cortisone injection within the 3 months prior to
surgery, smoking, obesity, and several comorbidities. The only preventive measure
with level I evidence was for the use of chlorhexidine wipes for cleansing the
skin in the days prior to surgery and for the use of ChloraPrep or DuraPrep over
povodine and iodine to prep the skin at the time of surgery. Level II-IV evidence
was found for other infection prevention methods such as intravenous antibiotic
prophylaxis. CONCLUSION: There are many risk factors associated with developing
an infection after elective shoulder surgery. Many preventive measures have been
described which may decrease the risk of infection; however, most lack a high
level evidence to support them. The findings of this systematic review are
clinically relevant as it has been shown that infection after shoulder surgery
results in poor patient-reported outcomes and pose a significant financial
burden. As surgeons the goal should be to prevent infections to avoid the
morbidity for patients and the increased cost for society. LEVEL OF EVIDENCE: IV
systematic review of literature.
PMID- 29340751
TI - Correction to: Improving the baking quality of bread wheat by genomic selection
in early generations.
AB - Unfortunately, the co-author, Dr. Gungor was missed out in the authorship of
original publication by mistake and it is updated now.
PMID- 29340752
TI - The effect of INDEHISCENT point mutations on silique shatter resistance in
oilseed rape (Brassica napus).
AB - KEY MESSAGE: This study elucidates the influence of indehiscent mutations on
rapeseed silique shatter resistance. A phenotype with enlarged replum-valve joint
area and altered cell dimensions in the dehiscence zone is described. Silique
shattering is a major factor reducing the yield stability of oilseed rape
(Brassica napus). Attempts to improve shatter resistance often include the use of
mutations in target genes identified from Arabidopsis (Arabidopsis thaliana). A
variety of phenotyping methods assessing the level of shatter resistance were
previously described. However, a comparative and comprehensive evaluation of the
methods has not yet been undertaken. We verified the increase of shatter
resistance in indehiscent double knock-down mutants obtained by TILLING with a
systematic approach comparing three independent phenotyping methods. A positive
correlation of silique length and shatter resistance was observed and accounted
for in the analyses. Microscopic studies ruled out the influence of different
lignification patterns. Instead, we propose a model to explain increased
shattering resistance of indehiscent rapeseed mutants by altered cell shapes and
sizes within the contact surfaces of replum and valves.
PMID- 29340753
TI - Can spelt wheat be used as heterotic group for hybrid wheat breeding?
AB - KEY MESSAGE: Spelt wheat is a distinct genetic group to elite bread wheat, but
heterosis for yield and protein quality is too low for spelt to be recommended as
heterotic group for hybrid breeding in wheat. The feasibility to switch from line
to hybrid breeding is currently a hot topic in the wheat community. One
limitation seems to be the lack of divergent heterotic groups within wheat
adapted to a certain region. Spelt wheat is a hexaploid wheat that can easily be
crossed with bread wheat and that forms a divergent genetic group when compared
to elite bread wheat. The aim of this study was to investigate the potential of
Central European spelt as a heterotic group for Central European bread wheat. We
performed two large experimental field studies comprising in total 43 spelt
lines, 14 wheat lines, and 273 wheat-spelt hybrids, and determined yield, heading
time, plant height, resistance against yellow rust, leaf rust, and powdery
mildew, as well as protein content and sedimentation volume. Heterosis of yield
was found to be lower than that of hybrids made between elite wheat lines.
Moreover, heterosis of the quality trait sedimentation volume was negative.
Consequently, spelt wheat does not appear suited to be used as heterotic group in
hybrid wheat breeding. Nevertheless, high combining abilities of a few spelt
lines with elite bread wheat lines make them interesting resources for pre
breeding in bread wheat. Thereby, the low correlation between line per se
performance and combining ability of these spelt lines shows the potential to
unravel the breeding value of genetic resources by crossing them to an elite
tester.
PMID- 29340754
TI - Preoperative evaluation of cochlear implantation through the round window
membrane in the facial recess using high-resolution computed tomography.
AB - PURPOSE: We evaluated the risk of cochlear implantation through the round window
membrane in the facial recess through a preoperative analysis of the angle
between the facial nerve-round window and the cranial midline using high
resolution temporal bone CT. METHODS: Temporal bone CT films of 176 patients with
profound sensorineural hearing loss at our hospital from 2013 to 2015 were
reviewed. The preoperative temporal bone CT scans of the patients were
retrospectively analysed. The vertical distance (d value) from the leading edge
of the facial nerve to the posterior wall of the external auditory canal and the
angle (alpha value) between the line from the leading edge of the facial nerve to
the midpoint of the round window membrane and the median sagittal line on the
round window membrane plane were measured. Based on intraoperative observation,
the round window membrane was divided into complete round window membrane
exposure (group A), partial exposure (group B), and unexposed (group C) groups,
and statistical analysis was performed. RESULTS: The alpha value could be
effectively measured for all 176 patients (62.60 +/- 7.12), and the d value could
be effectively measured for 95 cases (5.53 +/- 1.00). An analysis of the
correlation between the alpha and d values of these 95 cases found a negative
correlation. Of the 176 cases, one-way analysis of variance (ANOVA) showed that
the differences among the groups were significant [P = 0.000 (< 0.05)].
CONCLUSION: The angle (alpha value) between the line connecting the leading edge
of the facial nerve to the midpoint of the round window and the median sagittal
line measured in preoperative CT scans was associated with the difficulty of
intraoperatively exposing the round window membrane. When the alpha value was
larger than a certain degree, the difficulty of exposing the round window
membrane was increased. In such cases, the surgeon should fully expose the round
window membrane during surgery, which could result decrease the likelihood of
complications.
PMID- 29340755
TI - Multiple invasion speeds in a two-species integro-difference competition model.
AB - We study an integro-difference competition model for the case that two species
consecutively invade a habitat. We show that if a species spreads into a
traveling wave of its rival, or if two species expand their spatial ranges in
both directions, in a direction where open space is available, the species with
larger invasion speed can always establish a wave moving into open space with its
own speed. We demonstrate that when one species is stronger in competition, under
appropriate conditions, the speeds at which the boundaries between two species
move can be analytically determined. We find that in general there are multiple
invasion speeds in the model. It is possible for a species to develop two
separate waves propagating with different invasion speeds. It is also possible
for each species to establish a single wave spreading with distinct speeds in
both directions. The mathematical analysis relies on linear determinacy and new
techniques developed.
PMID- 29340756
TI - Differential effect of a patient-education transition intervention in adolescents
with IBD vs. diabetes.
AB - : Patient education programs (PEPs) to improve disease management are part of
standard and regular treatment in adolescents with diabetes. In Germany, youth
with inflammatory bowel disease (IBD) receive individual counseling but not PEPs
in group settings. Generic PEPs have been developed in order to improve
transition from child-centered to adolescent health services. The aim of the
study was to investigate the effects of a transition-oriented PEP on quality of
life (QoL) and self-management in young patients with IBD (PEP naive), compared
to patients with diabetes (familiar with PEPs). A 2-day transition workshop was
oriented at improving psychosocial skills and addressed both generic as well as
specific aspects of the condition. A controlled trial on the outcomes of a
generic transition-oriented PEP was conducted in 14- to 20-year-old patients with
IBD (n = 99) and diabetes (n = 153). Transition competence and QoL were assessed
at baseline and 6-month follow-up. Results show that the intervention lead to a
significant increase in QoL only in patients with IBD. The PEP significantly
improved transition competence in both groups, however to a higher extent in
subjects with IBD. CONCLUSION: Transition-oriented PEPs can have differential
effects in different patient groups. However, this needs further longitudinal
investigations. What is Known: * To date, evidence has accumulated concerning the
effectiveness of patient education programs (PEPs) in pediatric health care for
chronic conditions such as type 1 diabetes, asthma, atopic dermatitis, or obesity
but is less documented in inflammatory bowel disease (IBD). In particular, PEPs
in the transition period have not been investigated in youth with IBD. * The
current study focuses on evaluating a PEP for transition preparation and
management designed to be generically used across different chronic conditions
since many aspects of managing chronic conditions share commonalities across
conditions. The 2-day workshop included condition-specific modules adapted to the
specific medical needs but was otherwise similar in quality and organization
among different conditions. What is New: * The transition-oriented PEP was
effective in enhancing self-management and transition management skills in both
patients with IBD and diabetes; however, effects were higher in youth with IBD. A
significant impact of the intervention on patients' QoL compared to the control
group was only identified in youth with IBD. * We recommend that patients with
IBD have access to PEP as a standard treatment as well as to a transition program
during the course of illness.
PMID- 29340757
TI - Comparing brain activity patterns during spontaneous exploratory and cue
instructed learning using single photon-emission computed tomography (SPECT)
imaging of regional cerebral blood flow in freely behaving rats.
AB - Learning can be categorized into cue-instructed and spontaneous learning types;
however, so far, there is no detailed comparative analysis of specific brain
pathways involved in these learning types. The aim of this study was to compare
brain activity patterns during these learning tasks using the in vivo imaging
technique of single photon-emission computed tomography (SPECT) of regional
cerebral blood flow (rCBF). During spontaneous exploratory learning, higher
levels of rCBF compared to cue-instructed learning were observed in motor control
regions, including specific subregions of the motor cortex and the striatum, as
well as in regions of sensory pathways including olfactory, somatosensory, and
visual modalities. In addition, elevated activity was found in limbic areas,
including specific subregions of the hippocampal formation, the amygdala, and the
insula. The main difference between the two learning paradigms analyzed in this
study was the higher rCBF observed in prefrontal cortical regions during cue
instructed learning when compared to spontaneous learning. Higher rCBF during cue
instructed learning was also observed in the anterior insular cortex and in
limbic areas, including the ectorhinal and entorhinal cortexes, subregions of the
hippocampus, subnuclei of the amygdala, and the septum. Many of the rCBF changes
showed hemispheric lateralization. Taken together, our study is the first to
compare partly lateralized brain activity patterns during two different types of
learning.
PMID- 29340758
TI - Plants eavesdrop on cues produced by snails and induce costly defenses that
affect insect herbivores.
AB - Although induced defenses are widespread in plants, the degree to which plants
respond to herbivore kairomones (incidental chemicals that herbivores produce
independent of herbivory), the costs and benefits of responding to cues of
herbivory risk, and the ecological consequences of induced defenses remain
unclear. We demonstrate that undamaged tomatoes, Solanum lycopersicum, induce
defenses in response to a kairomone (locomotion mucus) of snail herbivores (Helix
aspersa). Induced defense had significant costs and benefits for plants: plants
exposed to snail mucus or a standard defense elicitor (methyl jasmonate, MeJA)
exhibited slower growth, but also experienced less herbivory by an insect
herbivore (Spodoptera exigua). We also find that kairomones from molluscan
herbivores lead to deleterious effects on insect herbivores mediated through
changes in plant defense, i.e., mucus-induced defenses of Solanum lycopersicum
reduced growth of S. exigua. These results suggest that incidental cues of
widespread generalist herbivores might be a mechanism creating variation in plant
growth, plant defense, and biotic interactions.
PMID- 29340759
TI - Cecum ulcer is a reliable endoscopic finding in cytomegalovirus colitis
concomitant with graft-versus-host disease after allogeneic hematopoietic stem
cell transplantation.
AB - Although graft-versus-host disease (GVHD) is the major complication of allogeneic
hematopoietic stem cell transplantation (allo-HSCT), cytomegalovirus (CMV)
reactivation also occurs in patients after allo-HSCT and these conditions often
clinically overlap. The aim of this study was to determine reliable endoscopic
findings of CMV colitis in patients with gastrointestinal graft-versus-host
disease (GI-GVHD). Patients after allo-HSCT who were histologically confirmed to
have GI-GVHD with or without CMV colitis and patients with an immunosuppressive
condition were retrospectively analyzed. We divided the patients into three
groups: GI-GVHD with CMV colitis (group A), GI-GVHD without CMV colitis (group
B), and CMV colitis without undergoing allo-HSCT (group C). From medical records,
the involved colorectal areas and endoscopic findings according to the groups
were compared. A total of 70 patients were divided into three groups (group A: n
= 19, group B: n = 28, group C: n = 23). Mucosal injuries in groups A and C
frequently occurred in the cecum including ileocecal valves. On the other hand,
there were no abnormal lesions on ileocecal valves in group B. Furthermore, ulcer
lesions were more frequently observed in groups A and C than in group B (p <
0.001). The sensitivity and specificity of mucosal injuries in the cecum for
prediction of CMV colitis were 89.5 and 76.5%, respectively, and mucosal injuries
in the cecum were more reliable findings than CMV antigenemia. Ulcer lesions in
the cecum are reliable endoscopic findings for CMV colitis in patients with GI
GVHD after allo-HSCT.
PMID- 29340760
TI - Infections associated with ruxolitinib: study in the French Pharmacovigilance
database.
PMID- 29340761
TI - Long-term efficacy and toxicity of rituximab plus fludarabine and mitoxantrone (R
FM) for gastric marginal zone lymphoma: a single-center experience and literature
review.
AB - There is no consensus about the best treatment option for patients with HP
negative gastric MALT lymphomas or persistent disease after HP eradication.We
have investigated fludarabine and mitoxantrone with rituximab (R-FM) as first
line treatment. A cohort of 13 patients was analyzed. Induction treatment
consisted of fludarabine (25 mg/m2 i.v. on days 2 to 4), mitoxantrone (10 mg/m2
i.v. on day 2), and rituximab (375 mg/m2 i.v. on day 1), for up to six cycles
every 28 days. All patients achieved a complete remission, a median of four
cycles was given. Treatment-related toxicities were mainly hematologic, with
grade 3-4 neutropenia observed in 11/13 patients (84.6%). One patient had grade 3
febrile neutropenia, two patients developed prolonged pancytopenia (15%), and one
patient experienced CMV reactivation at 2 months. After a median follow-up of 84
months, 1/13 had disease relapse and received total gastrectomy; estimated 10
year progression-free survival and overall survival were 92.4 and 100%,
respectively. Our study suggests R-FM regimen has a high long-term efficacy for
untreated HP-negative gastric MALT lymphoma patients and HP-positive patients who
failed HP eradication. The elevated incidence of grade 3-4 hematological
toxicity, yet manageable, makes this treatment less safe compared to rituximab in
combination with chlorambucil or bendamustine.
PMID- 29340762
TI - The role of endoscopy in the treatment of hydrocephalus associated with
aneurysmal malformation of the vein of Galen.
PMID- 29340763
TI - The retinal projection to the nucleus lentiformis mesencephali in zebra finch
(Taeniopygia guttata) and Anna's hummingbird (Calypte anna).
AB - In birds, the nucleus of the basal optic root (nBOR) and the nucleus lentiformis
mesencephali (LM) are retinal recipient nuclei involved in the analysis of optic
flow and the generation of the optokinetic response. In both pigeons and
chickens, retinal inputs to the nBOR arise from displaced ganglion cells (DGCs),
which are found at the margin of the inner nuclear and inner plexiform layers.
The LM receives afferents from retinal ganglion cells, but whether DGCs also
project to LM is a matter of debate. Previous work in chickens had concluded that
DGCs do not project to LM, but a recent study in pigeons found that both retinal
ganglion cells and DGCs project to LM. These findings leave open the question of
whether there are species differences with respect to the DGC projection to LM.
In the present study, we made small injections of retrograde tracer into the LM
in a zebra finch and an Anna's hummingbird. In both cases, retrogradely labeled
retinal ganglion cells and DGCs were observed. These results suggest that a
retinal input to the LM arising from DGCs is characteristic of most, if not all,
birds.
PMID- 29340764
TI - Correction to: Population data of 21 autosomal STR loci in the Hausa, Igbo and
Yoruba people of Nigeria.
AB - In the original paper author Alani Sulaimon Akanmu was erroneously omitted from
the author list. Prof. Akanmu has now been added as 4th author. Prof. Akanmu
acted as an academic supervisor of the study and additionally contributed to the
publication by reading, commenting and editing the manuscript.
PMID- 29340765
TI - Orotracheal tube as a risk factor for lower respiratory tract infection:
preliminary data from a randomised trial.
AB - PURPOSE: The aim of the study was to investigate whether polyurethane (PU)
endotracheal tubes, continuous measurements of cuff pressure and aspiration of
the subglottic space as a bundle of parameters could reduce patients' risk for
developing ventilator associated pneumonia (VAP). METHODS: Two groups of patients
that differed only in terms of endotracheal tubes and intubation intervention
were compared. Group A was ventilated using PU tubes a with conical cuff; they
also had continuous cuff pressure measurement and continuous subglottic
aspiration. Group B was ventilated using PVC tubes with a cylindrical cuff; the
patients underwent intermittent cuff pressure measurement and intermittent
subglottic aspiration. RESULTS: Seven patients in group A (13.2%) and 18 in group
B (36.0%) out of 103 were diagnosed with VAP. VAP patients were in general older,
stayed longer in the ICU and were ventilated significantly longer compared with
the patients with no VAP. Eight more patients in group B died compared with group
A. Moreover, subjects in group A survived longer. Patient age, hours on
mechanical ventilation, and days on an ICU were all positively associated with
the occurrence of VAP. CONCLUSIONS: Prevention parameters in ventilation (PU
cuff, conical cuff, continuous subglottic drainage and continuous cuff pressure
measurement) could prevent the incidence of VAP in ICU patients.
PMID- 29340766
TI - Wanted: a better cut-off value for the Epworth Sleepiness Scale.
AB - BACKGROUND: Excessive daytime sleepiness (EDS) is the main complaint in many
neurological sleep disorders, such as idiopathic hypersomnia, narcolepsy, or
obstructive sleep apnea/hypopnea syndrome (OSAS). The validity of the Epworth
Sleepiness Scale (ESS) as a screening tool for EDS remains controversial. We
therefore investigated (1) the interrelation of the ESS total score and the mean
sleep latency (MSL) during the multiple sleep latency test (MSLT) and (2) the
diagnostic accuracy of the ESS total score to detect EDS in patients with the
chief complaint of subjective EDS. METHODS: A total of 94 patients (48 males)
with subjective EDS were included in this study. Regression analyses and ROC
curve analyses were carried out to assess the predictive value of the ESS score
for MSL. RESULTS: The ESS score significantly predicted a shortened MSL (p =
0.01, beta = -0.29). After dichotomizing into two groups, the ESS score predicted
MSL only in patients with hypersomnia or narcolepsy (p = 0.01, beta = -0.33), but
not in patients with other clinical diagnoses (e. g. OSAS; p = 0.36, beta =
0.15). The ROC curve analyses indicated an optimal ESS cut-off value of 16 with a
sensitivity of 70%; however, specificity remained unsatisfactory (55.6%).
CONCLUSIONS: Our results suggest that the predictive value of the ESS score in
patients with subjective EDS is low and patient subgroup-specific (superior in
hypersomnia/narcolepsy vs. other diagnoses) and that the commonly used cut-off of
11 points may be insufficient for clinical practice.
PMID- 29340767
TI - Analysis of prognostic factors after resection of solitary liver metastasis in
colorectal cancer: a 22-year bicentre study.
AB - PURPOSE: The investigation of the predictors of outcome after hepatic resection
for solitary colorectal liver metastasis. METHODS: We recruited 350 patients with
solitary colorectal liver metastasis at the University Hospitals of Jena and
Magdeburg, who underwent curative liver resection between 1993 and 2014. All
patients had follow-up until death or till summer 2016. RESULTS: The follow-up
data concern 96.6% of observed patients. The 5- and 10-year overall survival
rates were 47 and 28%, respectively. The 5- and 10-year disease-free survival
rates were 30 and 20%, respectively. The analysis of the prognostic factors
revealed that the pT category of primary tumour, size and grade of the metastasis
and extension of the liver resection had no statistically significant impact on
survival and recurrence rates. In multivariate analysis, age, status of lymph
node metastasis at the primary tumour, location of primary tumour, time of
appearance of the metastasis, the use of preoperative chemotherapy and the
presence of extrahepatic tumour proved to be independent statistically
significant predictors for the prognosis. Moreover, patients with rectal cancer
had a lower intrahepatic recurrence rate, but a higher extrahepatic recurrence
rate. CONCLUSION: The long-term follow-up of patients with R0-resected liver
metastasis is multifactorially influenced. Age and comorbidity have a role only
in the overall survival. More than three lymph node metastasis reduced both the
overall and disease-free survival. Extrahepatic tumour had a negative influence
on the extrahepatic recurrence and on the overall survival. Neither overall
survival nor recurrence rates was improved using neoadjuvant chemotherapy.
PMID- 29340770
TI - [A fresh look at the German Survey on Aging].
PMID- 29340768
TI - The comparison of clinical outcomes in patients with acute myocardial infarction
and advanced chronic kidney disease on chronic hemodialysis versus off
hemodialysis.
AB - Acute myocardial infarction (AMI) is more frequently observed in patients with
chronic kidney disease (CKD) than in patients without CKD. Initial treatment
strategy for AMI includes primary percutaneous coronary intervention (PCI), which
requires substantial amount of contrast media. We hypothesized that the clinical
outcomes are comparable or worse in patients with AMI and advanced CKD off
chronic hemodialysis as compared to patients with AMI and advanced CKD on chronic
hemodialysis. The purpose of this study was to compare the clinical outcomes of
patients with AMI and advanced CKD on hemodialysis versus off hemodialysis. A
total of 148 patients with estimated glomerular filtration rate < 30 ml/min/1.73
m2 on admission were included and were divided into the HD group (n = 68) and non
HD group (n = 80). The length of hospitalization was significantly less in the HD
group (15.7 +/- 14.8 days) than in the non-HD group (22.4 +/- 21.3 days) (P =
0.01). In-hospital death was significantly less in the HD group (10.3%) than in
the non-HD group (25.0%) (P = 0.02). While the non-HD group was not significantly
associated with in-hospital death after controlling clinical covariates, the non
HD group (odd ratio 2.89, 95% confidence interval 1.03-8.12, P = 0.04) was
significantly associated with long hospitalization even after controlling
clinical covariates. In conclusion, as compared to advanced CKD on chronic
hemodialysis, advanced CKD off hemodialysis had higher morbidity and mortality in
patients with AMI. Advanced CKD off hemodialysis was closely associated with long
hospitalization even after controlling clinical factors.
PMID- 29340772
TI - The influence of passionate love on self-other discrimination during joint
action.
AB - Prior research on romantic relationships suggests that being in love involves a
blurring of self-other cognitive boundaries. However, this research has focused
so far on conceptual self-representation, related to the individual's traits or
interests. The present study tested the hypothesis that passionate love involves
a reduced discrimination between the self and the romantic partner at a bodily
level, as indexed by an increased Joint Simon effect (JSE), and we further
examined whether this self-other discrimination correlated with the passion felt
for the partner. As predicted, we found an increased JSE when participants
performed the Joint Simon Task with their romantic partner compared with a friend
of the opposite sex. Providing support for the self-expansion model of love (Aron
and Aron in Pers Relatsh 3(1):45-58, 1996), this result indicates that romantic
relationships blur the boundaries between the self and the romantic partner at a
bodily level. Furthermore, the strength of romantic feelings was positively
correlated with the magnitude of the JSE when sharing the task with the romantic
partner.
PMID- 29340771
TI - Predictive factors for pharyngocutaneous fistulization after total laryngectomy:
a Dutch Head and Neck Society audit.
AB - BACKGROUND: Incidences of pharyngocutaneous fistulization (PCF) after total
laryngectomy (TL) reported in the literature vary widely, ranging from 2.6 to
65.5%. Comparison between different centers might identify risk factors, but also
might enable improvements in quality of care. To enable this on a national level,
an audit in the 8 principle Dutch Head and Neck Centers (DHNC) was initiated.
METHODS: A retrospective chart review of all 324 patients undergoing laryngectomy
in a 2-year (2012 and 2013) period was performed. Overall PCF%, PCF% per center
and factors predictive for PCF were identified. Furthermore, a prognostic model
predicting the PCF% per center was developed. To provide additional data, a
survey among the head and neck surgeons of the participating centers was carried
out. RESULTS: Overall PCF% was 25.9. The multivariable prediction model revealed
that previous treatment with (chemo)radiotherapy in combination with a long
interval between primary treatment and TL, previous tracheotomy, near total
pharyngectomy, neck dissection, and BMI < 18 were the best predictors for PCF.
Early oral intake did not influence PCF rate. PCF% varied quite widely between
centers, but for a large extend this could be explained with the prediction
model. PCF performance rate (difference between the PCF% and the predicted PCF%)
per DHNC, though, shows that not all differences are explained by factors
established in the prediction model. However, these factors explain enough of the
differences that, compensating for these factors, hospital is no longer
independently predictive for PCF. CONCLUSIONS: This nationwide audit has provided
valid comparative PCF data confirming the known risk factors from the literature
which are important for counseling on PCF risks. Data show that variations in
PCF% in the DHNCs (in part) are explainable by the variations in these predictive
factors. Since elective neck dissection is a major risk factor for PCF, it only
should be performed on well funded indication.
PMID- 29340773
TI - Feature codes in implicit sequence learning: perceived stimulus locations
transfer to motor response locations.
AB - An important question in implicit sequence learning research is how the learned
information is represented. In earlier models, the representations underlying
implicit learning were viewed as being either purely motor or perceptual. These
different conceptions were later integrated by multidimensional models such as
the Dual System Model of Keele et al. (Psychol Rev 110(2):316-339, 2003).
According to this model, different types of sequential information can be learned
in parallel, as long as each sequence comprised only one single dimension (e.g.,
shapes, colors, or response locations). The term dimension, though, is
underspecified as it remains an open question whether the involved learning
modules are restricted to motor or to perceptual information. This study aims to
show that the modules of the implicit learning system are not specific to motor
or perceptual processing. Rather, each module processes an abstract feature code
which represents both response- and perception-related information. In two
experiments, we showed that perceiving a stimulus-location sequence transferred
to a motor response-location sequence. This result shows that the mere perception
of a sequential feature automatically leads to an activation of the respective
motor feature, supporting the notion of abstract feature codes being the basic
modules of the implicit learning system. This result could only be obtained,
though, when the task instructions emphasized the encoding of the stimulus
locations as opposed to an encoding of the color features. This limitation will
be discussed taking into account the importance of the instructed task set.
PMID- 29340774
TI - 'Exercise to me is a scary word': perceptions of fatigue, sleep dysfunction, and
exercise in people with fibromyalgia syndrome-a focus group study.
AB - Fibromyalgia syndrome (FMS) is a common and complex chronic pain condition.
Exercise is recommended in the management of the FMS; however, people with FMS
often find exercise exacerbates their condition and causes overwhelming fatigue.
The objective of this study was to explore the perceptions of fatigue and sleep
dysfunction, and exercise in people with FMS. Three, 60-90 min focus groups were
conducted with people with FMS (n = 14). Participants were recruited from patient
support groups who had experienced therapeutic exercise in the management of
their condition. Focus groups were video and audio recorded and transcriptions
analysed for thematic content by three independent evaluators. Fatigue, sleep
dysfunction, and pain were universally reported by participants. The over-arching
theme to emerge was a lack of understanding of the condition by others. A huge
sense of loss was a major sub-theme and participants felt that they had
fundamentally changed since the onset of FMS. Participants reported that they
were unable to carry out their normal activities, including physical activity and
exercise. The invisibility of FMS was associated with the lack of understanding
by others, the sense of loss, and the impact of FMS. People with FMS perceive
that there is a lack of understanding of the condition among health care
professionals and the wider society. Those with FMS expressed a profound sense of
loss of their former 'self'; part of this loss was the ability to engage in
normal physical activity and exercise.
PMID- 29340776
TI - Ectopic Cushing's syndrome secondary to olfactory neuroblastoma.
AB - We present the case of a patient with Cushing's syndrome secondary to ectopic
ACTH secretion. A MR of the head showed a left-sided nasal mass extending down
from the cribriform plate. The patient underwent endoscopic resection with nearly
complete removal of the mass. Histological examination showed an ACTH-secreting
olfactory neuroblastoma (ONB). The patient's cortisol levels returned to normal
range after surgery and have remained normal for over a year. ONB is a rare cause
for ectopic ACTH secretion. This case highlights the diagnostic and management
difficulties in patients with ectopic ACTH secretion, and provides a brief review
of ONB.
PMID- 29340775
TI - Global versus local mechanisms of temperature sensing in ion channels.
AB - Ion channels turn diverse types of inputs, ranging from neurotransmitters to
physical forces, into electrical signals. Channel responses to ligands generally
rely on binding to discrete sensor domains that are coupled to the portion of the
channel responsible for ion permeation. By contrast, sensing physical cues such
as voltage, pressure, and temperature arises from more varied mechanisms. Voltage
is commonly sensed by a local, domain-based strategy, whereas the predominant
paradigm for pressure sensing employs a global response in channel structure to
membrane tension changes. Temperature sensing has been the most challenging
response to understand and whether discrete sensor domains exist for pressure and
temperature has been the subject of much investigation and debate. Recent
exciting advances have uncovered discrete sensor modules for pressure and
temperature in force-sensitive and thermal-sensitive ion channels, respectively.
In particular, characterization of bacterial voltage-gated sodium channel
(BacNaV) thermal responses has identified a coiled-coil thermosensor that
controls channel function through a temperature-dependent unfolding event. This
coiled-coil thermosensor blueprint recurs in other temperature sensitive ion
channels and thermosensitive proteins. Together with the identification of ion
channel pressure sensing domains, these examples demonstrate that "local" domain
based solutions for sensing force and temperature exist and highlight the
diversity of both global and local strategies that channels use to sense physical
inputs. The modular nature of these newly discovered physical signal sensors
provides opportunities to engineer novel pressure-sensitive and thermosensitive
proteins and raises new questions about how such modular sensors may have evolved
and empowered ion channel pores with new sensibilities.
PMID- 29340777
TI - Answer to the Letter to the Editor of Yi Liu et al. concerning "Spinal movement
and dural sac compression during airway management in a cadaveric model with
atlanto-occipital instability" by Liao S, Schneider NRE, Weilbacher F et al.
(2017) Eur Spine J. doi:10.1007/s00586-017-5416-9.
PMID- 29340778
TI - Successful surgery for a neuromuscular scoliosis patient by pulmonary
rehabilitation with forced vital capacity below 30.
AB - A rare case of a 15-year-old male patient with neuromuscular scoliosis with
forced vital capacity (FVC) below 30%, who went through a successful surgery
without any pulmonary complications, is reported herein. The patient had obvious
asymmetric shoulders and poor exercise tolerance. The Cobb's angle of the main
thoracic curve was 62.8 degrees , and FVC in sitting position was 18% of
predictive value. After skull traction and pulmonary rehabilitation, the FVC was
still below 30%, and he finally went through surgery under this serious
condition. By early pulmonary rehabilitation using home ventilator, he
successfully recovered without any pulmonary complications. The patient had
complete symptom remission and no deterioration of Cobb's angle was found during
follow-up.
PMID- 29340779
TI - Dose, image quality and spine modeling assessment of biplanar EOS micro-dose
radiographs for the follow-up of in-brace adolescent idiopathic scoliosis
patients.
AB - PURPOSE: The aim of this study was to compare the radiation dose, image quality
and 3D spine parameter measurements of EOS low-dose and micro-dose protocols for
in-brace adolescent idiopathic scoliosis (AIS) patients. METHODS: We
prospectively included 25 consecutive patients (20 females, 5 males) followed for
AIS and undergoing brace treatment. The mean age was 12 years (SD 2 years, range
8-15 years). For each patient, in-brace biplanar EOS radiographs were acquired in
a standing position using both the conventional low-dose and micro-dose
protocols. Dose area product (DAP) was systematically recorded. Diagnostic image
quality was qualitatively assessed by two radiologists for visibility of
anatomical structures. The reliability of 3D spine modeling between two operators
was quantitatively evaluated for the most clinically relevant 3D radiological
parameters using intraclass correlation coefficient (ICC). RESULTS: The mean DAP
for the posteroanterior and lateral acquisitions was 300 +/- 134 and 433 +/- 181
mGy cm2 for the low-dose radiographs, and 41 +/- 19 and 81 +/- 39 mGy cm2 for
micro-dose radiographs. Image quality was lower with the micro-dose protocol. The
agreement was "good" to "very good" for all measured clinical parameters when
comparing the low-dose and micro-dose protocols (ICC > 0.73). CONCLUSION: The
micro-dose protocol substantially reduced the delivered dose (by a factor of 5-7
compared to the low-dose protocol) in braced children with AIS. Although image
quality was reduced, the micro-dose protocol proved to be adapted to radiological
follow-up, with adequate image quality and reliable clinical measurements. These
slides can be retrieved under Electronic Supplementary Material.
PMID- 29340780
TI - Health-related quality of life in outpatients with schizophrenia: factors that
determine changes over time.
AB - PURPOSE: The objective of this study was to analyze the clinical factors
associated with changes in HRQoL in outpatients with schizophrenia using both
generic and condition-specific HRQoL scales. METHODS: Adult outpatients with
schizophrenia at least 18 years of age who did not have an acute psychotic
exacerbation in the 3 months prior to baseline were recruited. PANSS dimensions
were calculated based on Lindenmayer et al.'s five factors. HRQoL data were
assessed by patients using the Schizophrenia Quality of Life Scale (SQLS), the
Short Form-36 (SF-36), and the EuroQol-5 Dimension (EQ-5D) questionnaires.
RESULTS: Out of the 1345 patients included at baseline, 1196 (89%) were evaluated
at 12 months. Regression models showed that the factor most consistently
associated with HRQoL at endpoint was change in the PANSS negative symptoms
score. A decrease in the PANSS negative symptoms score from baseline to 1 year
was associated with a decrease in HRQoL during the same period. There were also
significant associations of the change in PANSS excitatory factor with all the
HRQoL scales except the SF-36 PCS. Female gender was associated with a decrease
in all HRQoL ratings. There was also a relationship between years since onset and
HRQoL. The longer the time since illness onset, the larger the decrease in HRQoL.
CONCLUSIONS: This study has found that, in outpatients with schizophrenia,
changes in negative and excitement symptoms may have a greater an association
with HRQoL than changes in positive, cognitive and depressive symptoms.
PMID- 29340782
TI - Strigeid parasites of Circus buffoni from Argentina, with the description of a
new species of Parastrigea Szidat, 1928.
AB - Studying the Helminthological Collection of Museo de La Plata (MLP-He), several
specimens of digeneans, recovered parasitizing a long-winged harrier, Circus
buffoni (Accipitridae) from Buenos Aires Argentina, were analysed. The
morphological and morphometric analysis of these specimens revealed the presence
of two strigeid species, one of them new for science. Parastrigea buffoni n. sp.
is characterised by a forebody differentiated in a retractile cephalic region
with a large opening and a balloon-shaped collar region or collerette, suckers
located in cephalic region, holdfast organ with well development dorsal and
ventral lips that can emerge through opening, a claviform hindbody, a large
copulatory bursa with muscular ring (Ringnapf) and a genital cone well delimited,
crossed by a sinuous hermaphroditic duct with internal rugae. The euryxenous
parasite, Strigea falconis brasiliana, is briefly described, parasitizing a new
host. This is the first record of helminths parasitizing long-winged harrier.
PMID- 29340781
TI - Suicidal thoughts and behaviors among college students and same-aged peers:
results from the World Health Organization World Mental Health Surveys.
AB - PURPOSE: The primary aims are to (1) obtain representative prevalence estimates
of suicidal thoughts and behaviors (STB) among college students worldwide and (2)
investigate whether STB is related to matriculation to and attrition from
college. METHODS: Data from the WHO World Mental Health Surveys were analyzed,
which include face-to-face interviews with 5750 young adults aged 18-22 spanning
21 countries (weighted mean response rate = 71.4%). Standardized STB prevalence
estimates were calculated for four well-defined groups of same-aged peers:
college students, college attriters (i.e., dropouts), secondary school graduates
who never entered college, and secondary school non-graduates. Logistic
regression assessed the association between STB and college entrance as well as
attrition from college. RESULTS: Twelve-month STB in college students was 1.9%, a
rate significantly lower than same-aged peers not in college (3.4%; OR 0.5; p <
0.01). Lifetime prevalence of STB with onset prior to age 18 among college
entrants (i.e., college students or attriters) was 7.2%, a rate significantly
lower than among non-college attenders (i.e., secondary school graduates or non
graduates; 8.2%; OR 0.7; p = 0.03). Pre-matriculation onset STB (but not post
matriculation onset STB) increased the odds of college attrition (OR 1.7; p <
0.01). CONCLUSION: STB with onset prior to age 18 is associated with reduced
likelihood of college entrance as well as greater attrition from college. Future
prospective research should investigate the causality of these associations and
determine whether targeting onset and persistence of childhood-adolescent onset
STB leads to improved educational attainment.
PMID- 29340783
TI - Identification of bat trypanosomes from Minas Gerais state, Brazil, based on 18S
rDNA and Cathepsin-L-like targets.
AB - Several bat species can be infected by trypanosomes, but there is not much
information about which of these parasites infect bats from Triangulo Mineiro and
Alto Paranaiba, Minas Gerais state, Brazil, a formerly endemic region for
Trypanosoma cruzi, the causative agent of Chagas disease. The aim of this study
was to describe, characterize, and identify the presence of trypanosomes in bats.
The captured bats (448) belong to four families and to 19 different species. Of
those, 37 bats were found to be positive for trypanosomes by microhematocrit,
(infection rate 8.3%) and 27 were positive after hemoculture analysis. Initially,
the isolates were identified by PCR (18S rDNA, 24Salpha rDNA, spliced leader,
COII RFLP-PCR) using primers originally designed for T. cruzi. PCRs (18S rDNA,
24Salpha rDNA) showed compatible bands for TcI, whereas COII RFLP-PCR showed a
similar pattern associated to TcII. However, there was no DNA amplification using
spliced leader as a target, revealing a discrepancy between the results.
Phylogenetic analysis of Cathepsin L-like and 18S rDNA sequences proved that 15
of the isolates corresponded to Trypanosoma cruzi marinkellei and one to
Trypanosoma dionisii. These results revealed that the diversity of trypanosome
species in a region considered endemic for Chagas disease is greater than
previous descriptions. All this can confirm the necessity of using DNA sequencing
approaches in order to determinate trypanosomes species isolated from bats.
PMID- 29340784
TI - A new flesh fly species (Diptera: Sarcophagidae) parasitic on leptodactylid
frogs.
AB - Here we describe a new species of sarcophagid fly reared from larvae found
feeding on three species of leptodactylid frogs collected in subtropical
Corrientes Province in northeastern Argentina. Our species description is based
on adult male and female external morphology and genitalia. Adult males and
females of the new species were associated with certainty because all specimens
studied were reared from single clutches of larvae on each of three infested
frogs. Thus, adult males and females reared from each clutch were siblings that
emerged almost simultaneously. The paper provides line drawings, high-resolution
photographs, and SEM images to aid in identifying Lepidodexia (Notochaeta)
adelina sp. nov. and to distinguish the new species from its closely related
congeners. We include brief notes on the host species and on larval feeding
behavior of L. (N.) adelina. This is the first and only species in the genus
Lepidodexia reported to parasitize leptodactylid frogs. Further, our observations
reported here are the first to fully document a completed life cycle by
sarcophagid fly larvae on three different species of leptodactylid frogs and the
only well-documented case of myiasis of an amphibian in Argentina.
PMID- 29340785
TI - Nitric oxide acts downstream of abscisic acid in molybdenum-induced oxidative
tolerance in wheat.
AB - KEY MESSAGE: Our study first reveals that Mo mediates oxidative tolerance through
ABA signaling. Moreover, NO acts downstream of ABA signaling in Mo-induced
oxidative tolerance in wheat under drought stress. Nitric oxide (NO) is related
to the improvement of molybdenum (Mo)-induced oxidative tolerance. While the
function of Mo in abscisic acid (ABA) synthesis and in mediating oxidative
tolerance by the interaction of ABA and NO remain to be studied. The -Mo and +Mo
treatment-cultivated wheat was separated and subsequently was pretreated with AO
inhibitor, ABA synthesis inhibitor, exogenous ABA, NO scavenger, NO donor or
their combinations under polyethylene glycol 6000 (PEG)-stimulated drought stress
(PSD). The AO activity and ABA content were increased by Mo in wheat under PSD,
however, AO inhibitor decreased AO activity, correspondingly reduced ABA
accumulation, suggesting that AO involves in the regulation of Mo-induced ABA
synthesis. Mo enhanced activities and expressions of antioxidant enzyme, while
these effects of Mo were reversed by AO inhibitor and ABA synthesis inhibitor due
to the decrease of ABA content, but regained by exogenous ABA, indicating that Mo
induces oxidative tolerance through ABA. Moreover, NO scavenger inhibited
activities of antioxidant enzyme caused by Mo and exogenous ABA, but the
inhibitions were eliminated by NO donor, indicating that NO is involved in ABA
pathway in the regulation of Mo-induced oxidative tolerance in wheat under PSD.
Finally, we proposed a scheme for the mechanism of Mo-induced oxidative
tolerance.
PMID- 29340786
TI - In silico identification and experimental validation of amino acid motifs
required for the Rho-of-plants GTPase-mediated activation of receptor-like
cytoplasmic kinases.
AB - KEY MESSAGE: Several amino acid motifs required for Rop-dependent activity were
found to form a common surface on RLCKVI_A kinases. This indicates a unique
mechanism for Rho-type GTPase-mediated kinase activation in plants. Rho-of-plants
(Rop) G-proteins are implicated in the regulation of various cellular processes,
including cell growth, cell polarity, hormonal and pathogen responses. Our
knowledge about the signalling pathways downstream of Rops is continuously
increasing. However, there are still substantial gaps in this knowledge. One
reason for this is that these pathways are considerably different from those
described for yeast and/or animal Rho-type GTPases. Among others, plants lack all
Rho/Rac/Cdc42-activated kinase families. Only a small group of plant-specific
receptor-like cytoplasmic kinases (RLCK VI_A) has been shown to exhibit Rop
binding-dependent in vitro activity. These kinases do not carry any known GTPase
binding motifs. Based on the sequence comparison of the Rop-activated RLCK VI_A
and the closely related but constitutively active RLCK VI_B kinases, several
distinguishing amino acid residues/motifs were identified. All but one of these
were found to be required for the Rop-mediated regulation of the in vitro
activity of two RLCK VI_A kinases. Structural modelling indicated that these
motifs might form a common Rop-binding surface. Based on in silico data mining,
kinases that have the identified Rop-binding motifs are present in Embryophyta
but not in unicellular green algae. It can, therefore, be supposed that Rops
recruited these plant-specific kinases for signalling at an early stage of land
plant evolution.
PMID- 29340788
TI - The impact of advanced maternal age on the outcome of twin pregnancies.
AB - PURPOSE: To assess the effect of advanced maternal age on the obstetrics and
neonatal outcome of twin pregnancies. METHODS: A retrospective study of 716
dichorionic-diamniotic twin pregnancies delivered at our institute. The study
population was divided into two groups: women aged 35-39 years (group A, n = 142)
and women aged >= 40 years (Group B, n = 48). The control group consisted of
women younger than 35 years (group C, n = 516). RESULTS: The rate of cesarean
section (CS) was significantly higher among women older than 35 years compared to
the control group (A 76.8% and B 87.5% vs C 65.7%, P = 0.001). Women older than
35 years were also at higher risk for developing hypertensive disorders (A 7.0%,
B 14.6%, vs C 5.4%, P = 0.04). On multivariate regression analysis, maternal age
was found to be independently associated with a higher rate of CS (odds ratio vs
reference group C: group A 1.6, 95% CI 1.08-2.6; group B 3.2, 95% CI 1.3-7.8).
There was no difference between the groups in the rate of neonatal complications.
CONCLUSION: Women with twin pregnancy, older than 35 years, have a significantly
higher rate of CS and hypertensive disorder. This rate increases with maternal
age, with no increased rate of neonatal complications.
PMID- 29340787
TI - A profilin gene promoter from switchgrass (Panicum virgatum L.) directs strong
and specific transgene expression to vascular bundles in rice.
AB - KEY MESSAGE: A switchgrass vascular tissue-specific promoter (PvPfn2) and its 5'
end serial deletions drive high levels of vascular bundle transgene expression in
transgenic rice. Constitutive promoters are widely used for crop genetic
engineering, which can result in multiple off-target effects, including
suboptimal growth and epigenetic gene silencing. These problems can be
potentially avoided using tissue-specific promoters for targeted transgene
expression. One particularly urgent need for targeted cell wall modification in
bioenergy crops, such as switchgrass (Panicum virgatum L.), is the development of
vasculature-active promoters to express cell wall-affective genes only in the
specific tissues, i.e., xylem and phloem. From a switchgrass expression atlas we
identified promoter sequence upstream of a vasculature-specific switchgrass
profilin gene (PvPfn2), especially in roots, nodes and inflorescences. When the
putative full-length (1715 bp) and 5'-end serial deletions of the PvPfn2 promoter
(shortest was 413 bp) were used to drive the GUS reporter expression in stably
transformed rice (Oryza sativa L.), strong vasculature-specificity was observed
in various tissues including leaves, leaf sheaths, stems, and flowers. The
promoters were active in both phloem and xylem. It is interesting to note that
the promoter was active in many more tissues in the heterologous rice system than
in switchgrass. Surprisingly, all four 5'-end promoter deletions, including the
shortest fragment, had the same expression patterns as the full-length promoter
and with no attenuation in GUS expression in rice. These results indicated that
the PvPfn2 promoter variants are new tools to direct transgene expression
specifically to vascular tissues in monocots. Of special interest is the very
compact version of the promoter, which could be of use for vasculature-specific
genetic engineering in monocots.
PMID- 29340789
TI - Fully sialylated alpha-chain of complement 4-binding protein (A2160): a novel
prognostic marker for epithelial ovarian carcinoma.
AB - PURPOSE: Fully sialylated alpha-chain of complement 4-binding protein (A2160) is
a member of the glycoprotein family and has recently been identified as a
diagnostic biomarker for epithelial ovarian cancer. This study examined the
utility of A2160 as a prognostic biomarker for this disease. METHODS: This is a
retrospective analysis of prospectively collected plasma samples from 93 women
with stage I-IV epithelial ovarian cancer who underwent primary cytoreductive
surgery between 2009 and 2014. Pretreatment A2160 levels were correlated to
clinico-pathological factors and survival outcome. RESULTS: Women with advanced
stage disease had significantly higher 2160 levels compared to those with early
stage disease (stage I-II versus III-IV, median 2.17-2.70 versus 5.31-8.70 U/mL,
P < 0.01). Women with high-grade serous ovarian carcinoma had higher A2160 levels
compared to other histologies (6.60 versus 3.01 U/mL, P = 0.05). Women who had
suboptimal cytoreduction had significantly higher A2160 levels than those who
achieved optimal/complete cytoreduction (7.02 versus 2.30-3.17 U/mL, P < 0.01).
On univariable analysis, higher A2160 levels were significantly associated with
decreased progression-free survival (64-100 versus 1-33%ile, 5-year rates 53.4
versus 78.9%, P = 0.029). After controlling for age, CA-125 level, cytoreductive
status, histology, and stage, higher A2160 levels remained an independent
prognostic factor for decreased progression-free survival (adjusted-hazard ratio
(HR) 2.48, 95% confidence interval (CI) 1.01-6.11, P = 0.049). Similarly, higher
A2160 levels were independently associated with decreased cause-specific survival
on multivariable analysis (adjusted-HR 3.07, 95% CI 1.19-7.93, P = 0.021).
CONCLUSION: Our study suggests that A2160 may be a useful prognostic biomarker
for epithelial ovarian cancer, and higher pretreatment levels of A2160 predicts
poor survival outcome.
PMID- 29340790
TI - An automated framework for QSAR model building.
AB - BACKGROUND: In-silico quantitative structure-activity relationship (QSAR) models
based tools are widely used to screen huge databases of compounds in order to
determine the biological properties of chemical molecules based on their chemical
structure. With the passage of time, the exponentially growing amount of
synthesized and known chemicals data demands computationally efficient automated
QSAR modeling tools, available to researchers that may lack extensive knowledge
of machine learning modeling. Thus, a fully automated and advanced modeling
platform can be an important addition to the QSAR community. RESULTS: In the
presented workflow the process from data preparation to model building and
validation has been completely automated. The most critical modeling tasks (data
curation, data set characteristics evaluation, variable selection and validation)
that largely influence the performance of QSAR models were focused. It is also
included the ability to quickly evaluate the feasibility of a given data set to
be modeled. The developed framework is tested on data sets of thirty different
problems. The best-optimized feature selection methodology in the developed
workflow is able to remove 62-99% of all redundant data. On average, about 19% of
the prediction error was reduced by using feature selection producing an increase
of 49% in the percentage of variance explained (PVE) compared to models without
feature selection. Selecting only the models with a modelability score above 0.6,
average PVE scores were 0.71. A strong correlation was verified between the
modelability scores and the PVE of the models produced with variable selection.
CONCLUSIONS: We developed an extendable and highly customizable fully automated
QSAR modeling framework. This designed workflow does not require any advanced
parameterization nor depends on users decisions or expertise in machine
learning/programming. With just a given target or problem, the workflow follows
an unbiased standard protocol to develop reliable QSAR models by directly
accessing online manually curated databases or by using private data sets. The
other distinctive features of the workflow include prior estimation of data
modelability to avoid time-consuming modeling trials for non modelable data sets,
an efficient variable selection procedure and the facility of output availability
at each modeling task for the diverse application and reproduction of historical
predictions. The results reached on a selection of thirty QSAR problems suggest
that the approach is capable of building reliable models even for challenging
problems.
PMID- 29340791
TI - Treatment of disabling headache with greater occipital nerve injections in a
large population of childhood and adolescent patients: a service evaluation.
AB - BACKGROUND: Pediatric headache disorders can be extremely disabling, with marked
reduction in the quality of life of children and their carers. Evidenced-based
options for the treatment of primary headache disorders with preventive
medication is limited and clinical outcomes are often unsatisfactory. Greater
occipital nerve injections represent a rapid and well-tolerated therapeutic
option, which is widely used in clinical practice in adults, and has previously
shown a good outcome in a pediatric population. METHODS: This service evaluation
reviewed greater occipital nerve injections performed unilaterally with 30 mg 1%
lidocaine and 40 mg methylprednisolone, to treat disabling headache disorders in
children and adolescents. RESULTS: We analyzed a total of 159 patients who
received 380 injections. Of the population, 79% had chronic migraine, 14% new
daily persistent headache, 4% a trigeminal autonomic cephalalgia, 3% secondary
headache and one patient had chronic tension-type headache. An improvement after
injection was seen in 66% (n = 105) of subjects, lasting on average 9 +/- 4
weeks. Improvement was seen in 68% of patients with chronic migraine, 67% with a
trigeminal autonomic cephalalgia and 59% with new daily persistent headache. Side
effects were reported in 8% and were mild and transient. Older age, female
gender, chronic migraine, increased number of past preventive use, medication
overuse and developing side effects were all associated with an increased
likelihood of positive treatment outcome. CONCLUSIONS: This large single centre
service evaluation confirms that unilateral injection of the greater occipital
nerve is a safe, rapid-onset and effective treatment strategy in disabling
headache disorders in children, with a range of diagnoses and severity of the
condition, and with minimal side effects.
PMID- 29340792
TI - Internal jugular vein variability predicts fluid responsiveness in cardiac
surgical patients with mechanical ventilation.
AB - BACKGROUND: To evaluate the efficacy of using internal jugular vein variability
(IJVV) as an index of fluid responsiveness in mechanically ventilated patients
after cardiac surgery. METHODS: Seventy patients were assessed after cardiac
surgery. Hemodynamic data coupled with ultrasound evaluation of IJVV and inferior
vena cava variability (IVCV) were collected and calculated at baseline, after a
passive leg raising (PLR) test and after a 500-ml fluid challenge. Patients were
divided into volume responders (increase in stroke volume >= 15%) and non
responders (increase in stroke volume < 15%). We compared the differences in
measured variables between responders and non-responders and tested the ability
of the indices to predict fluid responsiveness. RESULTS: Thirty-five (50%)
patients were fluid responders. Responders presented higher IJVV, IVCV and stroke
volume variation (SVV) compared with non-responders at baseline (P < 0.05). The
relationship between IJVV and SVV was moderately correlated (r = 0.51, P < 0.01).
The areas under the receiver operating characteristic (ROC) curves for predicting
fluid responsiveness were 0.88 (CI 0.78-0.94) for IJVV compared with 0.83 (CI
0.72-0.91), 0.97 (CI 0.89-0.99), 0.91 (CI 0.82-0.97) for IVCV, SVV, and the
increase in stroke volume in response to a PLR test, respectively. CONCLUSIONS:
Ultrasound-derived IJVV is an accurate, easily acquired noninvasive parameter of
fluid responsiveness in mechanically ventilated postoperative cardiac surgery
patients, with a performance similar to that of IVCV.
PMID- 29340793
TI - Neuroimaging Findings in Patients with Medication Overuse Headache.
AB - Medication overuse headache (MOH) is a secondary headache syndrome defined as the
deterioration of the headache associated with the overuse of analgesics. The
prevalence of MOH is 1-2% in the general population and even up to 50% in special
clinics. Overuse of abortive medications is highly associated with chronic daily
headaches and also a known risk factor for headache evolution. Possible
mechanisms include neural plasticity changes such as sensitization and defective
endogenous pain inhibition. Psychological studies have suggested dependence, even
addiction, in patients with MOH. Neuroimaging studies have provided valuable
information concerning MOH pathophysiology. Magnetic resonance imaging analyzed
by voxel-based morphometry showed gray matter volume changes in brain areas
participating the pain modulations. Changes of brain function at similar areas
have been revealed by positron emission tomography and functional magnetic
resonance imaging studies. Many of these changes were correlated with either
headache and/or analgesics parameters such as frequency and duration. These
changes are typically reversible after successful treatment. Though the cause or
consequence debate remains unsettled, we are more in favor of these findings as
maladaptive changes to the frequent headaches or medication overuse. Of these
brain areas involved in MOH, orbitofrontal cortex is of interest in several ways.
In an early positron emission tomography study, the hypometabolism persists after
successful treatment which implied a causal role. The following morphological
studies showed the orbitofrontal cortex volume could predict treatment responses.
Functional magnetic resonance imaging studies, task positive and also resting
state ones, also reported changes within the mesocorticolimbic dopamine system,
also known as reward system. Important brain areas of this system include ventral
tegmental area, striatum, and orbitofrontal cortex. The system plays an important
role in decision-making, dependence, and addiction, as implicated in
psychological studies of MOH. Further studies on neuromodulation of this system
may be considered in the treatment of MOH.
PMID- 29340794
TI - A unified description of colloidal thermophoresis.
AB - We use the dynamic length and time scale separation in suspensions to formulate a
general description of colloidal thermophoresis. Our approach allows an
unambiguous definition of separate contributions to the colloidal flux and
clarifies the physical mechanisms behind non-equilibrium motion of colloids. In
particular, we derive an expression for the interfacial force density that drives
single-particle thermophoresis in non-ideal fluids. The issuing relations for the
transport coefficients explicitly show that interfacial thermophoresis has a
hydrodynamic character that cannot be explained by a purely thermodynamic
consideration. Our treatment generalises the results from other existing
approaches, giving them a clear interpretation within the framework of non
equilibrium thermodynamics.
PMID- 29340795
TI - The sesquiterpene botrydial from Botrytis cinerea induces phosphatidic acid
production in tomato cell suspensions.
AB - MAIN CONCLUSION: The phytotoxin botrydial triggers PA production in tomato cell
suspensions via PLD and PLC/DGK activation. PLC/DGK-derived PA is partially
required for botrydial-induced ROS generation. Phosphatidic acid (PA) is a
phospholipid second messenger involved in the induction of plant defense
responses. It is generated via two distinct enzymatic pathways, either via
phospholipase D (PLD) or by the sequential action of phospholipase C and
diacylglycerol kinase (PLC/DGK). Botrydial is a phytotoxic sesquiterpene
generated by the necrotrophic fungus Botrytis cinerea that induces diverse plant
defense responses, such as the production of reactive oxygen species (ROS). Here,
we analyzed PA and ROS production and their interplay upon botrydial treatments,
employing tomato (Solanum lycopersicum) cell suspensions as a model system.
Botrydial induces PA production within minutes via PLD and PLC/DGK. Either
inhibition of PLC or DGK diminishes ROS generation triggered by botrydial. This
indicates that PLC/DGK is upstream of ROS production. In tomato, PLC is encoded
by a multigene family constituted by SlPLC1-SlPLC6 and the pseudogene SlPLC7. We
have shown that SlPLC2-silenced plants have reduced susceptibility to B. cinerea.
In this work, we studied the role of SlPLC2 on botrydial-induced PA production by
silencing the expression of SlPLC2 via a specific artificial microRNA. Upon
botrydial treatments, SlPLC2-silenced-cell suspensions produce PA levels similar
to wild-type cells. It can be concluded that PA is a novel component of the plant
responses triggered by botrydial.
PMID- 29340797
TI - Transcranial Doppler ultrasound in the ICU: it is not all sunshine and rainbows.
PMID- 29340796
TI - The complete plastome of macaw palm [Acrocomia aculeata (Jacq.) Lodd. ex Mart.]
and extensive molecular analyses of the evolution of plastid genes in Arecaceae.
AB - MAIN CONCLUSION: The plastome of macaw palm was sequenced allowing analyses of
evolution and molecular markers. Additionally, we demonstrated that more than
half of plastid protein-coding genes in Arecaceae underwent positive selection.
Macaw palm is a native species from tropical and subtropical Americas. It shows
high production of oil per hectare reaching up to 70% of oil content in fruits
and an interesting plasticity to grow in different ecosystems. Its domestication
and breeding are still in the beginning, which makes the development of molecular
markers essential to assess natural populations and germplasm collections.
Therefore, we sequenced and characterized in detail the plastome of macaw palm. A
total of 221 SSR loci were identified in the plastome of macaw palm.
Additionally, eight polymorphism hotspots were characterized at level of
subfamily and tribe. Moreover, several events of gain and loss of RNA editing
sites were found within the subfamily Arecoideae. Aiming to uncover evolutionary
events in Arecaceae, we also analyzed extensively the evolution of plastid genes.
The analyses show that highly divergent genes seem to evolve in a species
specific manner, suggesting that gene degeneration events may be occurring within
Arecaceae at the level of genus or species. Unexpectedly, we found that more than
half of plastid protein-coding genes are under positive selection, including
genes for photosynthesis, gene expression machinery and other essential plastid
functions. Furthermore, we performed a phylogenomic analysis using whole
plastomes of 40 taxa, representing all subfamilies of Arecaceae, which placed the
macaw palm within the tribe Cocoseae. Finally, the data showed here are important
for genetic studies in macaw palm and provide new insights into the evolution of
plastid genes and environmental adaptation in Arecaceae.
PMID- 29340798
TI - Diagnostic implications of a small-voxel reconstruction for loco-regional lymph
node characterization in breast cancer patients using FDG-PET/CT.
AB - BACKGROUND: We evaluated the diagnostic implications of a small-voxel
reconstruction for lymph node characterization in breast cancer patients, using
state-of-the-art FDG-PET/CT. We included 69 FDG-PET/CT scans from breast cancer
patients. PET data were reconstructed using standard 4 * 4 * 4 mm3 and small 2 *
2 * 2 mm3 voxels. Two hundred thirty loco-regional lymph nodes were included, of
which 209 nodes were visualised on PET/CT. All nodes were visually scored as
benign or malignant, and SUVmax and TBratio(=SUVmax/SUVbackground) were measured.
Final diagnosis was based on histological or imaging information. We determined
the accuracy, sensitivity and specificity for both reconstruction methods and
calculated optimal cut-off values to distinguish benign from malignant nodes.
RESULTS: Sixty-one benign and 169 malignant lymph nodes were included. Visual
evaluation accuracy was 73% (sensitivity 67%, specificity 89%) on standard-voxel
images and 77% (sensitivity 78%, specificity 74%) on small-voxel images (p =
0.13). Across malignant nodes visualised on PET/CT, the small-voxel score was
more often correct compared with the standard-voxel score (89 vs. 76%, p <
0.001). In benign nodes, the standard-voxel score was more often correct (89 vs.
74%, p = 0.04). Quantitative data were based on the 61 benign and 148 malignant
lymph nodes visualised on PET/CT. SUVs and TBratio were on average 3.0 and 1.6
times higher in malignant nodes compared to those in benign nodes (p < 0.001),
on standard- and small-voxel PET images respectively. Small-voxel PET showed
average increases in SUVmax and TBratio of typically 40% over standard-voxel PET.
The optimal SUVmax cut-off using standard-voxels was 1.8 (sensitivity 81%,
specificity 95%, accuracy 85%) while for small-voxels, the optimal SUVmax cut-off
was 2.6 (sensitivity 78%, specificity 98%, accuracy 84%). Differences in accuracy
were non-significant. CONCLUSIONS: Small-voxel PET/CT improves the sensitivity of
visual lymph node characterization and provides a higher detection rate of
malignant lymph nodes. However, small-voxel PET/CT also introduced more false
positive results in benign nodes. Across all nodes, differences in accuracy were
non-significant. Quantitatively, small-voxel images require higher cut-off
values. Readers have to adapt their reference standards.
PMID- 29340799
TI - Fully automated life support: an implementation and feasibility pilot study in
healthy pigs.
AB - BACKGROUND: Automated systems are available in various application areas all over
the world for the purpose of reducing workload and increasing safety. However,
such support systems that would aid caregivers are still lacking in the medical
sector. With respect to workload and safety, especially, the intensive care unit
appears to be an important and challenging application field. Whereas many closed
loop subsystems for single applications already exist, no comprehensive system
covering multiple therapeutic aspects and interactions is available yet. This
paper describes a fully closed-loop intensive care therapy and presents a
feasibility analysis performed in three healthy pigs over a period of 72 h each
to demonstrate the technical and practical implementation of automated intensive
care therapy. METHODS: The study was performed in three healthy, female German
Landrace pigs under general anesthesia with endotracheal intubation. An arterial
and a central venous line were implemented, and a suprapubic urinary catheter was
inserted. Electrolytes, glucose levels, acid-base balance, and respiratory
management were completely controlled by an automated fuzzy logic system based on
individual targets. Fluid management by adaption of the respective infusion rates
for the individual parameters was included. RESULTS: During the study, no manual
modification of the device settings was allowed or required. Homoeostasis in all
animals was kept stable during the entire observation period. All remote
controlled parameters were maintained within physiological ranges for most of the
time (free arterial calcium 73%, glucose 98%, arterial base excess 89%, and etCO2
98%). Subsystem interaction was analyzed. CONCLUSIONS: In the presented study, we
demonstrate the feasibility of a fully closed-loop system, for which we collected
high-resolution data on the interaction and response of the different subsystems.
Further studies should use big data approaches to analyze and investigate the
interactions between the subsystems in more detail.
PMID- 29340800
TI - Correction to: Psychiatric comorbidity and intimate partner violence among women
who inject drugs in Europe: a cross-sectional study.
AB - The original version of this article unfortunately missed the Acknowledgment.
PMID- 29340801
TI - Maternal depression trajectories from pregnancy to 3 years postpartum are
associated with children's behavior and executive functions at 3 and 6 years.
AB - The objective of this study was to investigate how patterns of maternal
depressive symptoms from mid-pregnancy to 3 years postpartum are associated with
children's behavior at age 3 years and executive functions. Maternal depressive
symptoms were measured from mid-pregnancy to 3 years postpartum. Growth mixture
modeling was used on standardized maternal depression scores (n = 147) to
identify trajectories. Children's behavioral problems and mental health
symptomatology (internalizing, externalizing, and attention deficit hyperactivity
disorder) were obtained at 3 and 6 years. EFs were assessed by a laboratory-based
computerized task and maternal-report at 6 years. Multivariable linear
regressions of children's outcomes against maternal depressive symptom
trajectories were conducted (n = 103). Three distinct patterns of maternal
depressive symptom trajectories were identified: low (n = 105), increasing (n =
27), and decreasing (n = 15). Children of mothers whose depressive symptoms
increased reported more problem behaviors at 3 years and poorer EFs at 6 years as
assessed by both instruments, but no significant differences in mental health
symptomatology at 6 years, relative to those whose mothers had consistently low
depressive symptoms. Children whose mothers became less depressed over time had
comparable levels of behavioral problems at age 3, executive functions, and
internalizing and externalizing scores at age 6; and fewer reported ADHD
behaviors at age 6, than those whose mothers remained less depressed over time.
If mothers' depressive symptoms improve over the first 3 years postpartum, their
children's outlook may be comparable to those whose mothers had consistently low
depressive symptoms.
PMID- 29340802
TI - Longitudinal trajectories of antidepressant use in pregnancy and the postnatal
period.
AB - Studies of antidepressant safety in pregnancy typically do not address complex
patterns of use throughout pregnancy. We performed longitudinal trajectory
modeling to describe patterns of antidepressant use in the first 32 weeks of
pregnancy, and test whether these trajectories are associated with a reduction in
birth weight or gestational age at delivery. Our study included 166 pregnant
women with deliveries between 2011 and 2015 who were prescribed an antidepressant
between 91 days prior to last menstrual period and 32 weeks of gestation. From
electronic medical records, we estimated average daily dose and cumulative dose
per week for the first 32 weeks of gestation and for the first 13 weeks
postnatal. We clustered women with similar utilization patterns using k-means
longitudinal modeling and assessed the associations between trajectory group and
birth weight and gestational age at delivery. We identified four cumulative dose
trajectory groups and three average daily dose trajectory groups in each period.
Relative to the lowest trajectory group, the highest trajectory group during
pregnancy was associated with reduced birth weight in multivariable analysis
(average daily highest trajectory vs. lowest trajectory beta - 314.1 g, 95% CI -
613.7, - 15.5) adjusted for depression severity score, maternal age, race, and
pregnancy smoking. Trajectory groups were not associated with gestational age at
delivery. The highest trajectory group of antidepressant use in pregnancy was
associated with a modest reduction in birth weight but not with gestational age
at delivery. Longitudinal trajectories allow for a dynamic visualization and
quantification of medication use among pregnant women.
PMID- 29340803
TI - Robust Exponential Memory in Hopfield Networks.
AB - The Hopfield recurrent neural network is a classical auto-associative model of
memory, in which collections of symmetrically coupled McCulloch-Pitts binary
neurons interact to perform emergent computation. Although previous researchers
have explored the potential of this network to solve combinatorial optimization
problems or store reoccurring activity patterns as attractors of its
deterministic dynamics, a basic open problem is to design a family of Hopfield
networks with a number of noise-tolerant memories that grows exponentially with
neural population size. Here, we discover such networks by minimizing probability
flow, a recently proposed objective for estimating parameters in discrete maximum
entropy models. By descending the gradient of the convex probability flow, our
networks adapt synaptic weights to achieve robust exponential storage, even when
presented with vanishingly small numbers of training patterns. In addition to
providing a new set of low-density error-correcting codes that achieve Shannon's
noisy channel bound, these networks also efficiently solve a variant of the
hidden clique problem in computer science, opening new avenues for real-world
applications of computational models originating from biology.
PMID- 29340804
TI - Erratum to: Tc-99m methoxyisobutylisonitrile bone marrow imaging for predicting
the levels of myeloma cells in bone marrow in multiple myeloma: correlation with
CD38/CD138 expressing myeloma cells.
PMID- 29340805
TI - Cardiorespiratory Fitness and Cardiovascular Disease Prevention: an Update.
AB - PURPOSE OF REVIEW: Cardiovascular diseases account for nearly one third of all
deaths globally. Improving exercise capacity and cardiorespiratory fitness (CRF)
has been an important target to reduce cardiovascular events. In addition, the
American Heart Association defined decreased physical activity as the fourth risk
factor for coronary artery disease. Multiple large cohort studies have evaluated
the impact of CRF on outcomes. In this review, we will discuss the role of CRF in
reducing cardiovascular morbidity and mortality. RECENT FINDINGS: Recent data
suggest that CRF has an important role in reducing not only cardiovascular and
all-cause mortality, but also incident myocardial infarction, hypertension,
diabetes, atrial fibrillation, heart failure, and stroke. Most recently, its role
in cancer prevention started to emerge. CRF protective effects have also been
seen in patients with prior comorbidities like prior coronary artery disease,
heart failure, depression, end-stage renal disease, and stroke. The prognostic
value of CRF has been demonstrated in various patient populations and
cardiovascular conditions. Higher CRF is associated with improved survival and
decreased incidence of cardiovascular diseases (CVD) and other comorbidities
including hypertension, diabetes, heart failure, and atrial fibrillation.
PMID- 29340806
TI - Distribution of IL28B and IL10 polymorphisms as genetic predictors of treatment
response in Pakistani HCV genotype 3 patients.
AB - There are over 10 million hepatitis C virus (HCV)-infected patients in Pakistan.
For these patients, a combination of interferon with ribavirin is the most
economical and easily available treatment. Single-nucleotide polymorphisms in
interleukin genes have been reported to be associated with the pathogenesis and
clearance of HCV, and sustained virologic response (SVR). An interleukin 28B
(IL28B) gene polymorphism has been shown to modify treatment outcomes, but the
effects of interleukin 10 (IL10) polymorphisms have not been previously assessed
in the Pakistani population. The present study was conducted with 302 subjects
categorized into two groups: 100 healthy volunteers (Group I) and 202 patients
with chronic HCV (Group II). Patients within Group II were further divided into
two subgroups according to therapeutic response: SVR (responders = 132) and NR
(non-responders/relapsers = 70). IL28B (rs8099917, rs12979860) and IL10
(rs1800872, rs1800871, rs1800896) gene polymorphisms were studied in all
subjects. A significant difference in the distribution of IL28B rs12979860C/T
genotypes between the two groups (p<0.05) was observed, while of the three IL10
polymorphisms, a significant difference was only shown for rs1800896 A/G.
Haplotype analysis (IL28B and IL10) showed a significant association of TTGTC and
TTGTA when comparing the groups. There was a strong association of the favorable
alleles rs8099917T and rs12979860C in the SVR group as compared with the NR group
(p<0.05), and rs1800896 also showed an association with the SVR group as compared
to the NR group (p<0.004). Haplotype analysis showed significant associations
when comparing the SVR and NR subgroups, i.e. TCATC (p=0.009), TTGTA (p=0.005),
TCATA (p<0.0005), TCACA (p=0.002), GTGCC (p=0.002) and TCGTC (p=0.005). IL28B
(rs8099917 and rs12979860) and IL10 (rs1800896) polymorphisms alone, or in
combination, are good predictors of therapeutic response in HCV-3a patients.
PMID- 29340807
TI - Long-Term Outcome of Infliximab Optimization for Overcoming Immunogenicity in
Patients with Inflammatory Bowel Disease.
AB - BACKGROUND: Preliminary data suggest that treatment optimization can reverse
immunogenicity and regain response in patients with IBD and secondary loss of
response (SLR) to anti-TNF therapy due to antidrug antibodies. However, data
regarding the long-term outcome of these patients are scarce. AIMS: We aimed to
investigate drug retention in IBD patients of whom infliximab was optimized to
overcome immunogenicity and variables associated with drug retention. METHODS:
This was a retrospective, multicenter study of consecutive IBD patients with
antibodies to infliximab (ATI), based on either proactive or reactive therapeutic
drug monitoring, who underwent infliximab optimization (increasing dose,
shortening interval, adding an immunomodulator, or combination) to overcome
immunogenicity from September 2012 to July 2015; they were followed through
December 2015. ATI were analyzed using the drug-tolerant Prometheus homogeneous
mobility shift assay. Drug retention was defined as no need for drug
discontinuation due to SLR or serious adverse event. RESULTS: Our cohort
consisted of 22 patients (Crohn's disease, n = 15). At the end of follow-up
[median, (IQR): 17.3 (10.5-32.8) months] 77% (15/22) of patients were still on
drug. Univariable Cox proportional hazards regression analysis identified first
detectable ATI titer as the only variable associated with drug retention (HR:
0.89; 95% CI: 0.82-0.98, p = 0.016). Receiver-operating characteristic analysis
identified an ATI titer < 8.8 U/mL associated with drug retention. CONCLUSIONS:
In real-life clinical practice, optimization of infliximab therapy can prevent
drug discontinuation in approximately 3/4 of patients with ATI, especially in
those with low titers. Large prospective studies are needed to confirm these
data.
PMID- 29340808
TI - Does advancement in stapling technology with triple-row and enhanced staple
configurations confer additional safety? A matched comparison of 340 stapled
ileocolic anastomoses.
AB - BACKGROUND: Over the past few decades, studies have focused on the safety of
stapled anastomosis, especially when compared to that of the handsewn technique.
However, studies on the improvement of stapling technology are limited. This
study aimed to investigate whether linear triple-row staples (tri-staples) had
any advantage over double-row staples. METHODS: This is a retrospective review of
all cases of functional end-to-end anastomoses with linear staplers performed at
two centers between 2005 and 2015. Data were retrieved from a prospectively
maintained database. Cases of anastomoses performed with double-row (DS) and
triple-row (TS) staples were matched according to propensity scores. The rates of
anastomotic leakage, bleeding, reoperation, and 30-day mortality were compared.
RESULTS: Functional end-to-end ileocolic anastomoses were performed in 563
consecutive patients during the study period. Double- and triple-row stapling
devices were used in 389 and 174 anastomoses, respectively. With propensity score
matching, 170 cases were chosen from each group. Both groups showed comparable
baseline characteristics. The anastomotic leakage, anastomotic bleeding, and
intra-abdominal collection rates were 2.4 and 0% (p = 0.123), 1.2 and 0% (p =
0.499), and 3.5 and 1.2% (p = 0.283) for DS and TS, respectively. The reoperation
and 30-day mortality rates were 5.9 and 1.8% (p = 0.048) and 0.6 and 1.2% (p =
1.000) for DS and TS, respectively. The median lengths of stay were 5 and 6 days
(p = 0.072) for DS and TS, respectively. CONCLUSION: Anastomoses with triple-row
staples tended to have a lower morbidity rate, but a significant advantage over
double-row staples was not demonstrated in this study.
PMID- 29340809
TI - Randomized controlled study of intraincisional infiltration versus
intraperitoneal instillation of standardized dose of ropivacaine 0.2% in post
laparoscopic cholecystectomy pain: Do we really need high doses of local
anesthetics-time to rethink!
AB - BACKGROUND: Earlier studies done to compare the efficacy of use of local
anesthetics at intraperitoneal location versus intraincisional use had utilized
equal amount of drugs at the two locations, usually 10-20 ml. Using this large
amount of drug in the small space of intraincisional location as compared to
similar amount of drug in large intraperitoneal space created an inadvertent bias
in favor of patients receiving the drug intraincisionally so these patients
naturally experienced less pain. AIMS AND OBJECTIVES: To conduct a randomized,
triple-blind, placebo-controlled study by standardizing dose of local anesthetic,
to compare the effectiveness of intraperitoneal against intraincisional use of
ropivacaine 0.2% for post-laparoscopic cholecystectomy pain relief. MATERIALS AND
METHODS: 294 patients underwent elective 4-port laparoscopic cholecystectomy.
Patients were triple blindly randomized. All patients received ~ 23 ml of
solution, of which 20 ml was given intraperitoneally (1 ml/cm; 16 ml along right
hemi-dome and 4 ml in gall bladder fossa) and ~ 3 ml intraincisionally (1 ml/cm
of length of incision). Solution was either normal saline or drug (0.2%
ropivacaine) depending on the group [controls (n = 86), intraperitoneal group (n
= 100), and intraincisional group (n = 108)]. 5 different pain scales were used
for assessment of overall pain. Pain scores were assessed at 5 points of time.
RESULTS: Patients in intraincisional group showed significantly less overall pain
and rescue analgesia requirement (p < 0.05). Intraincisional group showed
significantly less overall pain (p < 0.05) as compared to intraperitoneal group;
however, use of rescue analgesia was comparable in the two groups (p > 0.05); and
shoulder pain was significantly less in intraperitoneal group (p < 0.05).
CONCLUSION: The intraincisional use of injection ropivacaine at its minimum
concentration of 0.2% in minimal doses of 1 ml/cm at the end of procedure
provides significantly more post-operative analgesia as compared to
intraperitoneal group and controls. However, for controlling shoulder pain, the
use of intraperitoneal ropivacaine is desirable.
PMID- 29340810
TI - Ureteral stents increase risk of postoperative acute kidney injury following
colorectal surgery.
AB - BACKGROUND: Ureteral stents are commonly placed before colorectal resection to
assist in identification of ureters and prevent injury. Acute kidney injury (AKI)
is a common cause of morbidity and increased cost following colorectal surgery.
Although previously associated with reflex anuria, prophylactic stents have not
been found to increase AKI. We sought to determine the impact of ureteral stents
on the incidence of AKI following colorectal surgery. METHODS: All patients
undergoing colon or rectal resection at a single institution between 2005 and
2015 were reviewed using American College of Surgeons National Surgical Quality
Improvement Program dataset. AKI was defined as a rise in serum creatinine to >=
1.5 times the preoperative value. Univariate and multivariate regression analyses
were performed to identify independent predictors of AKI. RESULTS: 2910 patients
underwent colorectal resection. Prophylactic ureteral stents were placed in 129
patients (4.6%). Postoperative AKI occurred in 335 (11.5%) patients during their
hospitalization. The stent group demonstrated increased AKI incidence (32.6% vs.
10.5%; p < 0.0001) with bilateral having a higher rate than unilateral stents.
Hospital costs were higher in the stent group ($23,629 vs. $16,091; p < 0.0001),
and patients with bilateral stents had the highest costs. Multivariable logistic
regression identified predictors of AKI after colorectal surgery including age,
procedure duration, and ureteral stent placement. CONCLUSIONS: Prophylactic
ureteral stents independently increased AKI risk when placed prior to colorectal
surgery. These data demonstrate increased morbidity and hospital costs related to
usage of stents in colorectal surgery, indicating that placement should be
limited to patients with highest potential benefit.
PMID- 29340811
TI - A word of caution: never use tacks for mesh fixation to the diaphragm!
AB - BACKGROUND: The mesh fixation technique used in repair of hiatal hernias and
subxiphoid ventral and incisional hernias must meet strenuous requirements. In
the literature, there are reports of life-threatening complications with cardiac
tamponade and a high mortality rate on using tacks. The continuing practice of
tack deployment for mesh fixation to the diaphragm and esophageal hiatus should
be critically reviewed. METHODS: In a systematic search of the available
literature in May 2017, 23 cases of severe penetrating cardiac complications were
identified. The authors became aware of two other cases in which they acted as
medical experts. Furthermore, the instructions for use issued by the
manufacturers of the tacks were reviewed with regard to their deployment in the
diaphragm. RESULTS: Twenty-three of 25 cases (92%) with severe cardiac injuries
and subsequent cardiac tamponade were triggered by the use of tacks in the
diaphragm. In six cases (24%), these related to ventral and incisional hernias
with extension to the subxiphoid area, and in 19 cases (76%) to mesh-augmented
hiatoplasty. Twelve of 25 (48%) patients died as a result of pericardial and/or
heart muscle injury with cardiac tamponade despite heart surgery intervention. In
the tack manufacturers' instructions for use, their deployment in the diaphragm,
in particular in the vicinity of the heart, is contraindicated. Likewise, the
existing guidelines urgently advise against the use of tacks in the diaphragm,
recommending instead alternative fixation techniques. CONCLUSIONS: Tacks should
not be used for mesh fixation in the diaphragm above the costal arch.
PMID- 29340812
TI - Partial amniotic carbon dioxide insufflation (PACI) during minimally invasive
fetoscopic interventions on fetuses with spina bifida aperta.
AB - BACKGROUND: Percutaneous partial amniotic carbon dioxide insufflation (PACI) is
one of the most important means for improving visualization during minimally
invasive fetoscopic surgery of fetal spina bifida. The purpose of the present
study was to analyze maternal and fetal safety aspects of PACI in a recent
patient cohort and to present management improvements. METHODS: PACI under
general materno-fetal anesthesia was performed during 65 interventions for
fetoscopic patch coverage of fetal spina bifida aperta between 21 + 0 and 29 + 1
weeks of gestation. Filtered carbon dioxide was insufflated into the amniotic
cavity via three percutaneously introduced trocars. Maternal ventilatory and
hemodynamic parameters during PACI as well as insufflation pressures, BMI,
parity, and placental position were recorded and statistically analyzed in order
to detect potential risk groups. RESULTS: Maternal respiration parameters during
PACI showed a typical variation over time, which was similar in patients with BMI
<= 25 or BMI > 25. The necessary insufflation pressures were significantly higher
in nulliparae than multiparae. There was no statistically significant
relationship between insufflation pressure and maternal BMI, or between the
expired maternal carbon dioxide concentration (etCO2) and the placental position.
PACI was safe for all mothers and fetuses. Postnatal demise in one neonate, one
fetus, and two infants occurred unrelated to PACI and resulted from trisomy 13,
infection, and severe Chiari II malformations, respectively. CONCLUSION: PACI
seems safe in order to improve visualization of intraamniotic contents during
minimally invasive fetoscopic surgery. Nevertheless, continued assessments of its
benefits and risks are important.
PMID- 29340813
TI - Impact of laparoscopy in patients aged over 70 years requiring distal
pancreatectomy: a French multicentric comparative study.
AB - BACKGROUND: Few data are available concerning short-term results of minimally
invasive surgery in patients > 70 years old requiring distal pancreatectomy. The
aim of this study was to compare short-term results after laparoscopic (LDP)
versus open distal pancreatectomy (ODP) in this subgroup of patients. METHODS:
All patients > 70 years who underwent distal pancreatectomy in 3 expert centers
between 1995 and 2017 were included and data were retrospectively analyzed.
Demographic, intraoperative data and postoperative outcomes in LDP and ODP groups
were compared. RESULTS: A distal pancreatectomy was performed in 109 elderly
patients; LDP group included 53 patients while ODP group included 56. There were
55 (50.5%) males and 54 (49.5%) women with a median age of 75 years (range 70
87). Fifty (45.9%) patients were 70-74, 40 (36.7%) patients were 75-79, and 19
(17.4%) patients were over 80 years. Nine (8.2%) patients required conversion to
open surgery. The median operative time was not different between LDP and ODP
(204 vs. 220 min, p = 0.62). The intraoperative blood loss was significantly
lower in the LDP group (238 +/- 312 vs. 425 +/- 582 ml, p = 0.009) with no
difference regarding the intraoperative transfusion rate. 90-day mortality (0 vs.
5%, p = 0.42), overall complication (45.4 vs. 51.8%, p = 0.53), major
complication (18.2 vs. 12.5%, p = 0.43), grade B/C pancreatic fistula (6.8 vs.
7.1%, p = 0.71), were comparable in the 2 groups. Only postoperative confusion
rate was significantly lower in the LDP group (4.5 vs. 25%, p = 0.01). Median
length of stay was significantly lower in the LDP group (14 +/- 10 vs. 16 +/- 11
days, p = 0.04). R0 resection was performed in 94% of LDP patients and 89% in ODP
patients without significant difference (p = 0.73). CONCLUSIONS: The laparoscopic
approach seems to reduce blood loss, postoperative confusion, and length of stay
in elderly patients requiring distal pancreatectomy.
PMID- 29340814
TI - Comparison of mesh fixation devices for laparoscopic ventral hernia repair: an
experimental study on human anatomic specimens.
AB - BACKGROUND: As there is a lack of clarity in terms of the tensile strength of
mesh fixation for laparoscopic ventral hernia repair (LVHR), our aim was to
investigate the immediate tensile strength of currently available mesh fixation
devices on human anatomic specimens. METHODS: Sixteen recently deceased body
donators (mean body mass index of 24.4 kg/m2) were used to test the immediate
tensile strength (Newton) of 11 different LVHR mesh fixation devices. RESULTS:
Each of the 11 different laparoscopic fixation devices was tested 44 times. Non
articulating tackers provided higher fixation resistance to tensile stress in
comparison to articulating tackers (5.1-mm ReliaTackTM: 16.9 +/- 8.7 N vs. 12.2
+/- 5.6 N, p = 0.013; 7-mm ReliaTackTM: 19.8 +/- 9.4 N vs. 15.0 +/- 7.0 N, p =
0.007). Absorbable tacks with a greater length, i.e. >=6 mm (7-mm ReliaTackTM, 6
mm SorbaFixTM and 7.2-mm SecureStrapTM) had significantly higher fixation tensile
strength than tacks with a shorter length, i.e. < 6 mm (5.1-mm ReliaTackTM and
5.1-mm AbsorbaTackTM) (p < 0.001). Furthermore, transfascial sutures (PDS 2-0
sutures 26.3 +/- 5.6 N) provided superior fixation tensile strength than 5.1-mm
AbsorbaTackTM (13.6 +/- 7.3 N) and cyanoacrylate glues such as LiquiBand FIX8TM
(3.5 +/- 2.4 N) (p < 0.001, respectively). There was a significant deterioration
in fixation capacity in obese body donators with a body mass index > 30 kg/m2
(13.8 +/- 8.0 vs. 17.9 +/- 9.7 N, p = 0.044). CONCLUSIONS: Although articulating
laparoscopic tackers improve accessibility and facilitate the utilization of
tacks within the fixation weak spot adjacent to the trocar placement, an
articulating shaft that is not ergonomic to use may limit mechanisms of force
transmission. For mesh fixation in LVHR, transfascial sutures and tacks with a
longer length provide better immediate fixation tensile strength results.
PMID- 29340815
TI - Comparison between submucosal tunneling endoscopic resection and video-assisted
thoracoscopic enucleation for esophageal submucosal tumors originating from the
muscularis propria layer: a randomized controlled trial.
AB - BACKGROUND AND AIMS: Surgical resection is considered the first treatment option
for submucosal tumors (SMTs) originating from the muscularis propria layer while
submucosal tunneling endoscopic resection (STER) is proved to be a safe and
effective method for treating SMTs. This study aimed to compare video-assisted
thoracoscopic enucleation (VATE) with STER for treating esophageal SMTs. METHODS:
Sixty-six patients with small esophageal SMTs were prospectively randomized from
July 2014 to December 2015. After exclusion of 8 patients, 58 subjects scheduled
for STER or VATE were enrolled. Clinicopathological, endoscopic, and adverse
events (AEs) data were collected and analyzed between STER and VATE. RESULTS:
Forty-six males and 12 females with a mean age of 46.1 +/- 9.4 years were
randomized to the STER (n = 30) and VATE (n = 28) groups, respectively.
Demographics and lesion features were similar between the two groups. Median
procedure time was shorter in the STER group than the VATE group (44.5 vs. 106.5
min, P < 0.001); cost was lower in the STER group (4499.46 vs. 6137.32 USD, P =
0.010). Median decrease in hemoglobin levels post-procedure was - 1.6 g/L in the
STER group and 14.7 g/L after VATE (P = 0.001). Lower postoperative pain scores
were found in the STER group compared with the VATE group (2 vs. 4, P < 0.001).
No recurrent or residual tumors were found in either group. En bloc resection
rates, complete resection rates, hospital times, and post-procedure AEs were
similar between two groups. The en bloc resection rates for SMTs < 20.0 mm were
100% in both groups while STER achieved only 71.4% en bloc resection rate for
SMTs >= 20.0 mm. CONCLUSION: STER and VATE are comparably effective for
esophageal SMTs; however, STER is superior to VATE with shorter operation time
and decreased cost, and seems safer than VATE. STER is recommended for SMTs <
20.0 mm while VATE is recommended for SMTs with a transverse diameter > 35.0 mm.
Clinical trail registration statement: This study is registered at
http://www.chictr.org.cn/showproj.aspx?proj=4814 . The registration
identification number is ChiCTR-TRC-14004759. The registration date is April 30,
2014.
PMID- 29340816
TI - Expanding indications of robotic thyroidectomy.
AB - BACKGROUND: Robotic thyroidectomy has many advantages with comparable oncologic
safety over conventional open surgery in low-risk differentiated thyroid cancer
cases. However, there have been few reports on the outcomes of patients who have
been treated with robotic thyroidectomy for more advanced thyroid cancer. The aim
of this study was to investigate the validity of expanding indications of robotic
thyroidectomy for more advanced thyroid cancer. METHODS: The data of 80 patients
with thyroid cancer who underwent robotic total thyroidectomy between January
2013 and December 2014 performed by a single surgeon at Chung-Ang University
Hospital were retrospectively reviewed. Among them, 40 patients who had cancer
larger than 2 cm or suspicious capsular invasion, or central lymph node (LN)
metastasis in preoperative pathologic and radiologic examinations were
categorized into the more advanced thyroid cancer group and the remaining
patients into the early thyroid cancer group. We compared surgical safety and
surgical completeness parameters between the two groups. RESULTS: The patients in
more advanced thyroid cancer group had larger tumors, more extrathyroidal
extension, and higher T stages. Surgical safety parameters, such as
hypoparathyroidism, vocal cord palsy, and other complications did not differ
significantly between the two groups. Surgical completeness parameters, such as
the mean number of retrieved LNs, median values of the stimulated thyroglobulin
levels, and the proportion of patients with stimulated thyroglobulin levels less
than 1 ng/mL, also did not differ significantly. CONCLUSIONS: The outcomes of the
patients with more advanced thyroid cancer who were treated with robotic
thyroidectomy were comparable to those of the early cancer group patients. Well
designed investigations that are conducted at multiple centers are needed to
affirm the validity of expanding indications of robotic thyroidectomy.
PMID- 29340817
TI - Adenoma detection rate metrics in colorectal cancer surveillance colonoscopy.
AB - BACKGROUND: A target goal for screening adenoma detection rate (S-ADR) of >= 25%
has been set to define high-quality colonoscopy performance. However, there is no
current accepted target goal for ADR in colorectal cancer (CRC) surveillance.
This makes quality assessment challenging when physicians perform cancer
surveillance colonoscopy but minimal screening procedures. METHODS: In this
cohort study, consecutive colonoscopies performed at either Rush University
Medical Center or Rush Oak Park Hospital by a gastroenterologist or colorectal
surgeon in average risk screening population and CRC surveillance population were
reviewed retrospectively from 2006 to 2012 and prospectively from 2013 to 2016.
ADR in first surveillance colonoscopy following surgical resection of CRC (CRC
ADR) was reported in high-quality detectors (HQD) or low-quality detectors (LQD)
based on achievement of 25% ADR in consecutive screening colonoscopy in average
risk patients. Pearson's correlation was used to describe the association between
individual S-ADR and CRC-ADR for colonoscopists. RESULTS: There was a very strong
positive correlation (r = 0.88, p = 0.002) between ADR in average risk screening
and first time CRC surveillance. For HQD as defined by S-ADR >= 25% (n = 10
colonoscopists), the CRC-ADR was 37.7% (78/207, SD 8%) which was very similar to
their respective S-ADR of 33.4% (816/2440, p = 0.22). For LQD (n = 5
colonoscopists), the CRC-ADR was 20.2% (40/198) which was similar to their
respective S-ADR of 20.1% (119/591, p = 0.99). The CRC-ADR was significantly
higher for HQD than for LQD (37.7 vs. 20.2%, p < 0.0001). CONCLUSIONS: The major
finding of this study is a defined CRC-ADR for HQD based on the ability to
achieve S-ADR >= 25%. S-ADR strongly correlates with CRC-ADR. CRC-ADR is quite
similar to the colonoscopists' respective S-ADR for both HQD and LQD. For
colonoscopists who perform limited screening colonoscopies but do perform CRC
surveillance colonoscopies, ADR metrics similar to S-ADR to assess quality in
colonoscopy could be considered.
PMID- 29340818
TI - Changes in plasma albumin levels in early detection of infectious complications
after laparoscopic colorectal cancer surgery with ERAS protocol.
AB - BACKGROUND: Combination of laparoscopic approach with ERAS protocol in colorectal
surgery allows for an early discharge. However there is a risk that some of the
discharged patients are developing, asymptomatic at the time, infectious
complications. This may lead to a delay in diagnostics and proper treatment
introduction. We aimed to assess the usefulness of preoperative plasma albumin
concentration and their changes as indicators of infectious complications in
patients undergoing colorectal cancer surgery. METHODS: Prospective analysis
included 105 consecutive patients who underwent laparoscopic colorectal cancer
resection between August 2014 and September 2016. In all cases standardised 16
item perioperative care ERAS protocol was used (mean compliance > 85%). Patients
with IBD, distant metastases, undergoing emergency or multivisceral resection
were excluded. Blood samples were collected preoperatively and on POD 1, 2, 3.
Plasma albumin concentration was measured. Patients were divided into two groups
depending on the presence of infectious complications. We analysed the
differences in the levels of albumin and the dynamics of changes. RESULTS: Group
1-82 not complicated patients, Group 2-23 patients with at least one infectious
complication. Preoperatively, there were no significant differences in the levels
of serum albumin between those groups (Group 1-38.7 +/- 4.9 g/l; Group 2-37.7 +/-
5.0 g/l). In postoperative period, decrease was observed in both (POD 1: Group 1
36.5 +/- 4.2 g/l, Group 2-34.7 +/- 4.2 g/l, p = 0.07; POD 2: Group 1-36.2 +/- 4.1
g/l, Group 2-32.6 +/- 5.6 g/l, p = 0.01; POD 3: Group 1-36.0 +/- 4.4 g/l, Group 2
30.9 +/- 3.5 g/l, p = 0.01). The decrease was significantly greater in Group 2 on
POD 2 and 3. CONCLUSIONS: We showed that a regular measurement of albumin in the
early postoperative days may be beneficial in the detection of postoperative
infectious complications. Although changes in albumins are observed early after
surgery, this parameter is relatively unspecific.
PMID- 29340819
TI - Laparoscopic liver resection for colorectal liver metastasis patients allows
patients to start adjuvant chemotherapy without delay: a propensity score
analysis.
AB - BACKGROUND: Although adjuvant chemotherapy (AC) is widely used after liver
resection (LR) for colorectal liver metastasis (CRLM), surgical invasiveness may
lead to delay in starting AC, which is preferably started within 8 weeks
postoperative. We investigated whether laparoscopic liver resection (LLR) for
CRLM facilitates AC start without delay. METHODS: Between November 2014 and
December 2016, 117 consecutive CRLM patients underwent LR followed by AC. LLR and
OLR were performed in 30 and 87 patients, respectively. After propensity score
matching on clinical characteristics, oncologic features, and type of resection,
the time interval between liver resection and AC start was compared between LLR
(n = 22) and OLR (n = 44) groups. RESULTS: After propensity score matching, major
LR was performed in 8/22 (36%) and 15/44 (34%) cases of LLR and OLR groups,
respectively (P = 1.0). Clinical-pathological characteristic and intraoperative
findings were comparable between two groups. There was no significant difference
in postoperative complications between the two groups. The time interval between
liver resection and AC start was significantly shorter in LLR than in OLR group
(43 +/- 10 versus 55 +/- 18 days, P = 0.012). While 15/44 (34%) patients started
AC after 8 weeks postoperative in OLR group, all patients in LLR group started AC
within 8 weeks. CONCLUSIONS: LLR for CRLM is associated with quicker return to AC
when compared to OLR. The delivery of AC without delay allows CRLM patients to
optimize the oncologic treatment sequence.
PMID- 29340822
TI - A preclinical animal study of a novel, simple, and secure duct and vessel
occluder for laparoscopic surgery.
AB - BACKGROUND: Secure occlusion of large blood vessels and ductal structures is
critical to all surgeries and remains a challenge in many minimally invasive
procedures. This study compares in vivo use of the Amsel Occluder (AO) for secure
laparoscopic blood vessel and duct closure, with one of the many commercially
available hemoclips (Ligaclip(r)), in the porcine model. METHODS: Laparoscopic
closure of vessels and ducts was performed on 12 swine to compare the ease of
use, safety and efficacy of the AO with a hemoclip, as well as the tissue
response at > 30 days (10 swine). All vessels and ducts were occluded and then
transected between the occluding clips. Any bleeding or leakage was noted. In the
chronic study, confirmation of satisfactory vessel occlusion post nephrectomy was
determined by laparotomy as well as by contrast angiography and venography. The
tissue response and healing was evaluated by a histopathological study for the
effects of any biological incompatibilities. RESULTS: In the acute laparoscopic
study, a total of 24 occlusions between 2 and 10 mm were performed with the AO (n
= 19) and hemoclip (n = 5). In the chronic study, 5 nephrectomies (AO n = 3,
hemoclip N = 2) and 5 cholecystectomies (AO n = 3, hemoclip n = 2) were performed
with survival ranging from 42 to 72 days. One pig who sustained a splenic injury
at trocar insertion and suffered a delayed ruptured spleen with massive
hemorrhage on postoperative day 22. Unlike occlusion with the AO, multiple
hemoclips were used for each vessel occlusion. Histopathological examination
showed no difference in the tissue response and healing of the AO and hemoclip.
CONCLUSIONS: The Amsel Vessel occluder delivered laparoscopically provides an
occlusion similar to a hand-sewn transfixion suture, is simple to use, and
creates an occlusion which is not only more secure, but also as safe with respect
to the health of the surrounding tissues, as that of the widely used hemoclip
(Ligaclip(r)).
PMID- 29340821
TI - A novel and safe approach: middle cranial approach for laparoscopic right
hemicolon cancer surgery with complete mesocolic excision.
AB - BACKGROUND: Mastering right hemicolectomy techniques using laparoscopy in
colorectal cancer surgery is very difficult. Although the long-term prognosis of
laparoscopic right hemicolectomy (LRH) and complete mesocolic excision is
unquestionable, different surgeons have their own opinions on routes of
conducting LRH. OBJECTIVES: LRH surgery is very complex due to the upper
abdominal anatomical structure and vascular variation. Therefore, it has been
considered the most difficult of all colorectal cancer surgeries. Our innovative
middle cranial approach (MCA) was developed to avoid unnecessary injuries and
minimize the operative time, thereby reducing the patient's hospital stay and
improving their short-term prognosis. METHODS: We compared 90 colon cancer
patients who underwent the MCA between January 2016 and January 2017 with 82
patients who underwent the conventional central approach conducted by the same
group of physicians (with Dr Cui as the surgeon) from 2011 to 2015. A short-term
statistical analysis was performed. RESULTS: A total of 90 patients were
included: 43 men and 47 women. Twenty-three patients underwent abdominal surgery
(including stomach, rectum, and sigmoid colon surgery; appendectomy; and uterine
attachment surgery). The median age of these patients was 62.6 (28-85) years; the
median BMI was 22.9 (14.7-33.3) kg/m2; the mean bleeding volume was 53.9 (10-100)
ml; the mean tumour diameter was 5.7 (0.8-9) cm, and the average number of lymph
nodes detected was 19.2 (7-49). CONCLUSIONS: Our study showed that radical
resection of right-sided colon cancer using the MCA was safe and feasible for the
treatment of colorectal cancer patients.
PMID- 29340823
TI - Endoscopic perforations: what are the indications for surgery?
AB - BACKGROUND: Despite their low occurrence, endoscopic perforations (EPs) are
concerning. Some predictive factors have been identified, and EP management is
debated, whether non-surgical (medical and/or endoscopic) or surgical. The
objective was to elaborate a predictive score for surgical management of EP.
METHODS: All the patients addressed for upper and lower EP, except oesophageal
EP, were retrospectively included (2004-2015). Demographic data, endoscopic
features (indication, location, type), clinical, biological and radiological
presentations of EP were reviewed. Management of EP and outcomes were recorded. A
predictive score was constructed by multiple linear regression and a cut-off
value for surgical management was identified. Additional subgroup analysis was
performed according to the location of EP (upper and lower). RESULTS: Among 41150
endoscopic procedures, 44 patients (22 males, median age = 65 years [22-87])
presenting with EP were included (0.09%). Lower gastrointestinal (GI) endoscopy
was mostly performed (66%). EP diagnosis was immediate in 73% of the cases (n =
32). Non-surgical management was efficient in 2/3 cases treated medically alone,
and 18/20 cases treated by endoscopy. Surgical management was always successful
(n = 24/24). In case of peritonitis, surgery was systematically required, whereas
easily required in case of delayed diagnostic of EP. The EP score was based on
the presence of previous abdominal surgery, lower GI endoscopy and diagnostic
endoscopy. A cut-off EP score of 22.8% for surgery was chosen; it was associated
with a specificity and sensitivity of 40 and 100%, respectively. When subgroups
were analysed according to EP location, the EP score was still based on the
presence of previous abdominal surgery and diagnostic endoscopy. The cut-off was
6.3 and 73.3% for upper (specificity: 73%, sensitivity: 100%) and lower (89 and
45%) locations, respectively. CONCLUSION: The predictive EP score may avoid
inappropriate surgical management, as well as delayed surgery after non-surgical
management failure. Forthcoming study should prospectively validate this score.
PMID- 29340824
TI - A software-based tool for video motion tracking in the surgical skills assessment
landscape.
AB - BACKGROUND: The use of motion tracking has been proved to provide an objective
assessment in surgical skills training. Current systems, however, require the use
of additional equipment or specialised laparoscopic instruments and cameras to
extract the data. The aim of this study was to determine the possibility of using
a software-based solution to extract the data. METHODS: 6 expert and 23 novice
participants performed a basic laparoscopic cholecystectomy procedure in the
operating room. The recorded videos were analysed using Kinovea 0.8.15 and the
following parameters calculated the path length, average instrument movement and
number of sudden or extreme movements. RESULTS: The analysed data showed that
experts had significantly shorter path length (median 127 cm vs. 187 cm, p =
0.01), smaller average movements (median 0.40 cm vs. 0.32 cm, p = 0.002) and
fewer sudden movements (median 14.00 vs. 21.61, p = 0.001) than their novice
counterparts. CONCLUSION: The use of software-based video motion tracking of
laparoscopic cholecystectomy is a simple and viable method enabling objective
assessment of surgical performance. It provides clear discrimination between
expert and novice performance.
PMID- 29340825
TI - Laparoscopic surgery in colon cancer patients treated with chronic anti
thrombotic therapy.
AB - BACKGROUND: Anti-thrombotic medications are commonly used for the treatment and
prevention of cardiovascular diseases. Laparoscopic resection of colon cancer has
generally been accepted with favorable outcomes being reported in randomized
control trials. However, the safety and efficacy of laparoscopic surgery for
colon cancer patients receiving chronic anti-thrombotic therapy (AT) remain
unclear. METHODS: We identified 951 patients who underwent elective resection for
colon cancer between 2009 and 2016 from our database. Patients were classified
according to the surgical approach and chronic AT. Clinicopathological factors
and surgical outcomes were analyzed between patient groups. Patients' backgrounds
were matched using propensity scores in laparoscopic surgery. RESULTS: Anti
thrombotic drugs were chronically used in 135 patients. Among 714 patients who
underwent laparoscopy-assisted surgery, 96 received AT. The laparoscopic approach
was superior to open surgery in terms of bleeding, surgical site infections, and
hospital stay in patients receiving AT. In laparoscopy-assisted surgery, the AT
group patients were older and showed lower hemoglobin and albumin levels than
those not receiving AT (non-AT group), and were predominantly male. After
propensity score matching, estimated blood loss and operative times were similar
between the two groups (93 matched patients). The frequencies of postoperative
bleeding (2.2%) and thrombotic complications (0%) in the AT group did not
significantly differ from those in the non-AT group (1.1 and 0%, respectively).
Moreover, AT did not affect survivals. CONCLUSION: Laparoscopic approach appears
to be safer and beneficial for colonic cancer patients receiving long-term AT.
Bleeding and thrombotic events associated with laparoscopic surgery were not
significantly affected by AT.
PMID- 29340826
TI - Single-port laparoscopic surgery in uncomplicated acute appendicitis: a
randomized controlled trial.
AB - BACKGROUND: Single-port laparoscopic surgery (SPLS) is an alternative, minimally
invasive surgical approach for managing appendicitis. The aim of this randomized
trial was to evaluate the safety and efficacy of SPLS in uncomplicated
appendicitis. METHODS: Between December 2009 and November 2010, 194 patients with
radiologically diagnosed acute appendicitis were randomly allocated to undergo
either SPLS or multiport laparoscopic surgery (MPLS). Patients with
intraoperative findings of perforated appendicitis were excluded from the
analysis. The primary endpoint was perioperative morbidity. All data were
analyzed according to the intention-to-treat principle. RESULTS: Fourteen cases
were excluded from the analysis. Of the remaining 180 patients, 90 were assigned
to the SPLS group, and 90 to the MPLS group. Baseline characteristics were well
balanced between the groups. In the SPLS group, the rate of conversion to MPLS
was 11.1%. The operation time was 14.5 min longer for SPLS than for MPLS (p <
0.01), but there was no between-group difference in the rate of intraoperative
complications (SPLS, 4.4%; MPLS, 0%; p = 0.12) or postoperative complications
(SPLS, 4.4%; MPLS, 2.2%; p = 0.68). Compared to the MPLS group, the SPLS group
had higher cumulative dose of analgesics (tramadol; 73.9 vs. 51.7 mg, p = 0.04),
longer postoperative time to first passage of flatus (27.7 vs. 20.1 h, p < 0.01),
longer postoperative hospitalization (2.5 vs. 2.1 days, p < 0.05), and higher
total cost (1826.9 vs. 1662.4 USD, p < 0.01). CONCLUSIONS: This randomized trial
indicates that, compared to MPLS, SPLS does not increase the rate of
perioperative or postoperative complications in uncomplicated appendicitis, but
may have disadvantages such as increased operation time, later postoperative
functional recovery, longer hospital stay, and higher costs, although the
difference is minimal (ClinicalTrials.gov Identifier: NCT01007318).
PMID- 29340827
TI - Single-incision laparoscopic hepaticojejunostomy for children with perforated
choledochal cysts.
AB - BACKGROUND: Conventionally, perforated choledochal cyst (CDC) is a
contraindication of laparoscopic treatment. The current study is to evaluate
efficacy of single-incision laparoscopic hepaticojejunostomy (SILH) in children
with perforated CDCs. METHODS: One hundred and thirty-three children with
perforated CDCs who underwent SILHs in our hospital between August 2011 and
August 2017 were reviewed. RESULTS: Fifteen (11.3%) patients were converted to
open procedures due to severe adhesions and oozing. The mean age at SILH was 2.09
years (range 2 days-12.37 years). The average operative time was 3.23 h (range 2
5 h). The mean postoperative hospital stay was 6.25 days (range 4-16 days). The
mean time to full diet resumption was 2.18 days (range 2-6 days). The mean
duration of drainage was 3.71 days (range 3-10 days). The median follow-up period
was 24 months. Postoperative liver function tests and serum amylase levels
returned to normal within 1 year. Three (2.5%) patients required blood
transfusions because of extensive oozing from intramural micro-vessels of CDCs.
Two (1.7%) patients encountered duodenal injuries because of severe adhesions.
The duodenum was repaired with double-layer 5-0 PDS running sutures. One (0.8%)
patient with giant CDC had abdominal fluids because of extensive dissection of
intrapancreatic segment of CDC. He recovered after 10 days of drainage. None of
patients had bile leak, anastomotic stenosis, cholangitis, intrahepatic reflux,
pancreatic leak, pancreatic calculi formation, pancreatitis, Roux-loop
obstruction, or adhesive intestinal obstruction. CONCLUSIONS: Single-incision
laparoscopic hepaticojejunostomy is safe and effective for selected patients with
perforated CDCs in experienced hands.
PMID- 29340829
TI - Trends and surgical outcomes of laparoscopic versus open pyloromyotomy.
AB - BACKGROUND: Hypertrophic pyloric stenosis (HPS) is one of the most common
pediatric illnesses necessitating surgical intervention. Controversy remains over
the optimal surgical approach between laparoscopic pyloromyotomy (LP) and open
pyloromyotomy (OP). LP has gained acceptance for management of HPS in an era of
expanding minimal access surgical approaches to pediatric conditions. Several
studies suggest advantages of LP over OP; however, selection bias and small
sample sizes remain a concern. This study compares the outcomes of LP versus OP
using propensity score methods. METHODS: The 2013-2015 ACS NSQIP Pediatric PUF
was queried for all infants undergoing pyloromyotomy. The trend in the proportion
of infants undergoing LP was described and perioperative outcomes between the OP
and LP cohorts were compared using propensity score weighted regression models.
RESULTS: 4847 infants were identified to have undergone surgical pyloromyotomy.
The proportion of LP performed increased significantly from 59% in 2013 to 65.5%
in 2015 (p < 0.001). LP was associated with lower overall complications (1.4% vs
2.9%) (ORadj 0.52, 95% CI 0.34-0.80), surgical site-related complications (1.1%
vs 2.1%) (ORadj 0.52, 95% CI 0.32-0.84), and post-operative length of stay (1.5
days vs 1.9 days) (ORadj 0.89, 95% CI 0.81-0.98) without significant differences
in related re-operation (0.9% vs 0.9%) (ORadj 1.01, 95% CI 0.52-1.93) or
readmissions (1.4% vs 2.1%) (ORadj 0.73, 95% CI 0.46-1.17). CONCLUSIONS: Our
study demonstrates that LP is increasingly utilized for management of
hypertrophic pyloric stenosis and is associated with shorter length of stay, and
lower odds of surgical site-specific and overall complications without
differences in related re-operations. This study supports LP as a safe and
effective method for management of HPS.
PMID- 29340830
TI - Fabrication of SrGe2 thin films on Ge (100), (110), and (111) substrates.
AB - Semiconductor strontium digermanide (SrGe2) has a large absorption coefficient in
the near-infrared light region and is expected to be useful for multijunction
solar cells. This study firstly demonstrates the formation of SrGe2 thin films
via a reactive deposition epitaxy on Ge substrates. The growth morphology of
SrGe2 dramatically changed depending on the growth temperature (300-700 degrees
C) and the crystal orientation of the Ge substrate. We succeeded in obtaining
single-oriented SrGe2 using a Ge (110) substrate at 500 degrees C. Development
on Si or glass substrates will lead to the application of SrGe2 to high
efficiency thin-film solar cells.
PMID- 29340828
TI - Hiatal hernia recurrence following magnetic sphincter augmentation and posterior
cruroplasty: intermediate-term outcomes.
AB - BACKGROUND: We have previously reported short-term outcomes after hiatal hernia
repair (HHR) at the time of magnetic sphincter augmentation (MSA) for
gastroesophageal reflux disease (GERD). Here we report intermediate-term outcomes
and hernia recurrence rate after concomitant MSA and HHR. METHODS: This is a
retrospective cohort study of patients who underwent repair of a hiatal hernia 3
cm or larger at the time of MSA implantation between May 2009 and December 2015.
The primary endpoint was hiatal hernia recurrence identified by routine
postoperative videoesophagography or endoscopy. Recurrence was defined by a 2 cm
or greater upward displacement of the stomach through the diaphragmatic
esophageal hiatus. Secondary endpoints included cessation of proton-pump
inhibitor (PPI), persistent dysphagia requiring intervention, and GERD health
related quality-of-life (HRQL) scores 1 year from surgery. RESULTS: During the
study period, 47 of 53 (89%) patients underwent concomitant MSA with HHR and
complied with surveillance. Hiatal hernias ranged from 3 to 7 cm (mean 4 +/- 1).
Mean clinical follow-up time was 19 months (range 1-39). GERD-HRQL score
decreased from 20.3 to 3.1 (p < .001), 89% of patients remained off PPIs, and 97%
of patients reported improvement or resolution of symptoms. Two recurrent hiatal
hernias were identified on surveillance imaging for a recurrence rate of 4.3% at
a mean 18 (+/- 10) months after initial operation. Persistent dysphagia occurred
in 13% (6/47) over the first year, which resolved after a single balloon dilation
in 67% (4/6). Two patients elected for device removal due to dilation-refractory
dysphagia and persistent reflux symptoms. CONCLUSION: Concomitant magnetic
sphincter augmentation and hiatal hernia repair in patients with gastroesophageal
reflux disease and a moderate-sized hiatal hernia demonstrates durable subjective
reflux control and an acceptable hiatal hernia recurrence rate at 1- to 2-year
follow-up.
PMID- 29340831
TI - Noninvasive quantification of left-to-right shunt by phase contrast magnetic
resonance imaging in secundum atrial septal defect: the effects of breath holding
and comparison with invasive oximetry.
AB - To investigate the effect of breath-holding on left-to-right shunts in patients
with a secundum atrial septal defect (ASD). Thirty-five consecutive patients with
secundum ASDs underwent right heart catheterization and invasive oximetry. Phase
contrast magnetic resonance imaging (MRI) was performed for the main pulmonary
artery and ascending aorta. All measurements were obtained during free breathing
(FB) (quiet breathing; no breath-hold), expiratory breath-hold (EBH), and
inspiratory breath-hold (IBH). Pulmonary circulation flow (Qp) and systemic
circulation flow (Qs) were calculated by multiplying the heart rate by the stroke
volume. Measurements during FB, EBH, and IBH were compared, and the differences
compared to invasive oximetry were evaluated. There were significant differences
among the measurements during FB, EBH, and IBH for Qp (FB, 7.70 +/- 2.68; EBH,
7.18 +/- 2.34; IBH, 6.88 +/- 2.51 l/min); however, no significant difference was
found for Qs (FB, 3.44 +/- 0.74; EBH, 3.40 +/- 0.83; IBH, 3.40 +/- 0.86 l/min).
There were significant differences among the measurements during FB, EBH, and IBH
for Qp/Qs (FB, 2.38 +/- 1.12; EBH, 2.24 +/- 0.95; IBH, 2.14 +/- 0.97). Qp/Qs
during FB and EBH correlated better with Qp/Qs measured by invasive oximetry than
did IBH. The limit of agreement was smaller for EBH than for FB and IBH. In
patients with secundum ASDs, Qp/Qs significantly decreased with breath-holding.
The accuracy of the Qp/Qs measurement by MRI compared with invasive oximetry
during EBH was higher than during FB and IBH.
PMID- 29340832
TI - Sacral neuromodulation in patients with congenital faecal incontinence. Special
issues and review of the literature.
AB - BACKGROUND: The aim of the present study was to evaluate the effectiveness of
sacral neuromodulation (SNM) as a treatment for congenital faecal incontinence
(FI). METHODS: A retrospective study was conducted on patients with congenital FI
who had SNM surgery at our institution between October 2005 and June 2013. An
initial percutaneous nerve evaluation was performed, and patients with an
improvement of more than 50% in their symptoms had permanently implants for SNM
treatment. RESULTS: There were 4 patients who received a permanent implant. Mean
duration of follow-up was 67.5 months (range 45-135 months). At last follow-up, 2
patients maintained significant improvement with SNM, 1 was explanted after 4
years of treatment due to infection but remained asymptomatic and SNM failed in
the remaining patient who went on to graciloplasty. CONCLUSIONS: SNM may be of
value for treating FI in patients with anorectal malformations.
PMID- 29340833
TI - Short-term outcomes of transanal haemorrhoidal dearterialization versus tissue
selecting technique.
PMID- 29340834
TI - Limited daily feeding and intermittent feeding have different effects on regional
brain energy homeostasis during aging.
AB - Albeit aging is an inevitable process, the rate of aging is susceptible to
modifications. Dietary restriction (DR) is a vigorous nongenetic and
nonpharmacological intervention that is known to delay aging and increase
healthspan in diverse species. This study aimed to compare the impact of
different restricting feeding regimes such as limited daily feeding (LDF, 60% AL)
and intermittent feeding (IF) on brain energy homeostasis during aging. The
analysis was focused on the key molecules in glucose and cholesterol metabolism
in the cortex and hippocampus of middle-aged (12-month-old) and aged (24-month
old) male Wistar rats. We measured the impact of different DRs on the expression
levels of AMPK, glucose transporters (GLUT1, GLUT3, GLUT4), and the rate-limiting
enzyme in the cholesterol synthesis pathway (HMGCR). Additionally, we assessed
the changes in the amounts of cholesterol, its metabolite, and precursors
following LDF and IF. IF decreased the levels of AMPK and pAMPK in the cortex
while the increased levels were detected in the hippocampus. Glucose metabolism
was more affected in the cortex, while cholesterol metabolism was more influenced
in the hippocampus. Overall, the hippocampus was more resilient to the DRs, with
fewer changes compared to the cortex. We showed that LDF and IF differently
affected the brain energy homeostasis during aging and that specific brain
regions exhibited distinct vulnerabilities towards DRs. Consequently, special
attention should be paid to the DR application among elderly as different phases
of aging do not respond equally to altered nutritional regimes.
PMID- 29340835
TI - Repurposed FDA-approved drugs targeting genes influencing aging can extend
lifespan and healthspan in rotifers.
AB - Pharmaceutical interventions can slow aging in animals, and have advantages
because their dose can be tightly regulated and the timing of the intervention
can be closely controlled. They also may complement environmental interventions
like caloric restriction by acting additively. A fertile source for therapies
slowing aging is FDA approved drugs whose safety has been investigated. Because
drugs bind to several protein targets, they cause multiple effects, many of which
have not been characterized. It is possible that some of the side effects of
drugs prescribed for one therapy may have benefits in retarding aging. We used
computationally guided drug screening for prioritizing drug targets to produce a
short list of candidate compounds for in vivo testing. We applied the virtual
ligand screening approach FINDSITEcomb for screening potential anti-aging protein
targets against FDA approved drugs listed in DrugBank. A short list of 31
promising compounds was screened using a multi-tiered approach with rotifers as
an animal model of aging. Primary and secondary survival screens and cohort life
table experiments identified four drugs capable of extending rotifer lifespan by
8-42%. Exposures to 1 uM erythromycin, 5 uM carglumic acid, 3 uM capecitabine,
and 1 uM ivermectin, extended rotifer lifespan without significant effect on
reproduction. Some drugs also extended healthspan, as estimated by mitochondria
activity and mobility (swimming speed). Our most promising result is that rotifer
lifespan was extended by 7-8.9% even when treatment was started in middle age.
PMID- 29340836
TI - Primary culture of lung fibroblasts from hyperoxia-exposed rats and a
proliferative characteristics study.
AB - Lung fibrosis is an ultimate consequence of bronchopulmonary dysplasia (BPD)
which shows the excessive proliferation of lung fibroblasts (LFs). To find a
better model for studying the role of LFs in hyperoxia-induced lung fibrosis at
the cellular level, we isolated LFs from the lung tissue of hyperoxia- and
normoxia-exposed rat lungs on postnatal days 7, 14 and 21 for primary culture to
study their proliferative behavior. In the present study, the LF predominance was
> 95% in our culture method. The LFs isolated from rats exposed to hyperoxia in
vivo showed significantly greater proliferation than that from normoxia-exposed
rats. Flow cytometry revealed that percentage of LFs in S and G2/M stage
increased, and proportion in the G0/G1 stage declined at the same time. A greater
presence of myofibroblasts in LFs isolated from rats exposed to hyperoxia
compared with those exposed to normoxia. In addition, elevated collagen level,
transforming growth factor-beta and connective tissue growth factor protein
expression in conditioned medium were also found in hyperoxia LFs. These data
demonstrate that hyperoxia promotes LFs proliferation, myofibroblast
transdifferentiation and collagen synthesis in a time-dependent manner. The
primary culture of LFs from hyperoxia-exposed rats is a feasible method for
studying the pathogenesis and treatment of lung fibrosis caused by BPD at the
cellular level.
PMID- 29340837
TI - Exacerbation of autoimmune hemolytic anemia induced by the first dose of
programmed death-1 inhibitor pembrolizumab: a case report.
AB - Immune checkpoint inhibitors (ICIs) have demonstrated efficacy against various
types of cancers. In addition to immune-related adverse events (irAEs) induced by
ICIs, exacerbation of baseline autoimmune disease has been occasionally reported.
This is the first report of autoimmune hemolytic anemia (AIHA) exacerbated by
pembrolizumab. An 82-year-old Japanese male was diagnosed with lung
adenocarcinoma 2 years ago. The patient had chronic anemia with positive direct
and indirect Coombs test prior to initiating pembrolizumab therapy at a nearby
hospital. However, a definitive diagnosis of AIHA was not made at that time.
Seventeen days after the first dose of pembrolizumab, the patient was admitted to
the Kobe City Medical Center General Hospital with severe hemolytic anemia (Hb
3.6 g/dL). After thorough examinations including bone marrow biopsy, the patient
was diagnosed with pre-existing AIHA exacerbated by pembrolizumab therapy. Two
weeks after treatment with prednisone, the levels of hemoglobin became stable
with the reduced frequency of blood transfusion and improvements of hemolytic
findings on blood tests and the patient was discharged from the hospital. This
case report highlighted the importance of determining the patient's pre-existing
autoimmune status associated with chronic anemia prior to initiating treatment
with ICIs.
PMID- 29340838
TI - Text-based phenotypic profiles incorporating biochemical phenotypes of inborn
errors of metabolism improve phenomics-based diagnosis.
AB - Phenomics is the comprehensive study of phenotypes at every level of biology:
from metabolites to organisms. With high throughput technologies increasing the
scope of biological discoveries, the field of phenomics has been developing rapid
and precise methods to collect, catalog, and analyze phenotypes. Such methods
have allowed phenotypic data to be widely used in medical applications, from
assisting clinical diagnoses to prioritizing genomic diagnoses. To channel the
benefits of phenomics into the field of inborn errors of metabolism (IEM), we
have recently launched IEMbase, an expert-curated knowledgebase of IEM and their
disease-characterizing phenotypes. While our efforts with IEMbase have realized
benefits, taking full advantage of phenomics requires a comprehensive curation of
IEM phenotypes in core phenomics projects, which is dependent upon contributions
from the IEM clinical and research community. Here, we assess the inclusion of
IEM biochemical phenotypes in a core phenomics project, the Human Phenotype
Ontology. We then demonstrate the utility of biochemical phenotypes using a text
based phenomics method to predict gene-disease relationships, showing that the
prediction of IEM genes is significantly better using biochemical rather than
clinical profiles. The findings herein provide a motivating goal for the IEM
community to expand the computationally accessible descriptions of biochemical
phenotypes associated with IEM in phenomics resources.
PMID- 29340839
TI - The cumulative incidence and risk factors of postoperative inguinal hernia in
patients undergoing radical prostatectomy.
AB - BACKGROUND: The aim of this study is to investigate the cumulative incidence and
risk factors of postoperative inguinal hernia (PIH) in patients undergoing
radical prostatectomy, i.e., laparoscopic prostatectomy (LRP) and robot-assisted
laparoscopic prostatectomy (RARP). METHODS: This study included 1124 patients who
had undergone radical prostatectomy or transurethral resection of bladder tumor
from 2011-2016. We compared the cumulative incidence of PIH in the radical
prostatectomy groups (460; LRP 341, RARP 119) and the control group (664;
transurethral resection of bladder tumor), and we then analyzed the risk factors
(age, operative methods, previous abdominal operative history, thickness and
width of external oblique muscle and rectus muscle, thickness of abdominal
subcutaneous fat layer at Hesselbach's triangle level, body mass index, prostate
specific antigen, operative time, specimen weight, Gleason score, and pathology T
stage) of PIH in the radical prostatectomy groups. RESULTS: The median follow-up
period in this study was 39.6 months. In Kaplan-Meier curve analysis, the
cumulative incidence of PIH was 5.3, 4.2, and 0.5% for the LRP, RARP, and control
groups, respectively (p < 0.001). Multiple logistic regressions showed that
thickness of external oblique muscle and width of rectus muscle were significant
risk factors (p < 0.001 and p = 0.027). CONCLUSIONS: PIH is considered to be one
of the complications of LRP and RARP. Moreover, we suggest that if the thickness
of the muscle is <7.3 mm, thoughtful surgical manipulation is needed for radical
prostatectomy, and care should be taken to determine whether hernia occurs during
follow-up.
PMID- 29340840
TI - Application of gamma irradiation knowledge in tissue sterilisation: inactivation
of malaria parasite.
AB - Malaria is one of the exclusion criteria used in selecting tissue donors and the
absence of this information can lead to rejection of tissues for transplant. The
studies on the malaria parasite have been confined to low dose attenuation of
parasites in blood for transfusion purposes. There is no published information
relating to the inactivation of malaria parasites with irradiation for the
sterilisation of tissues. A dose-surviving parasite population following
radiation was replotted using D0 value from a published paper whereby D10 value
of 41 Gy was obtained. Calculation of sterilisation dose for achieving SAL 10-6
of malaria parasites demonstrated the effectiveness of the sterilisation dose of
25 kGy being used in tissue banking.
PMID- 29340820
TI - The development and validation of a scoring tool to predict the operative
duration of elective laparoscopic cholecystectomy.
AB - BACKGROUND: The ability to accurately predict operative duration has the
potential to optimise theatre efficiency and utilisation, thus reducing costs and
increasing staff and patient satisfaction. With laparoscopic cholecystectomy
being one of the most commonly performed procedures worldwide, a tool to predict
operative duration could be extremely beneficial to healthcare organisations.
METHODS: Data collected from the CholeS study on patients undergoing
cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used
to study operative duration. A multivariable binary logistic regression model was
produced in order to identify significant independent predictors of long (> 90
min) operations. The resulting model was converted to a risk score, which was
subsequently validated on second cohort of patients using ROC curves. RESULTS:
After exclusions, data were available for 7227 patients in the derivation
(CholeS) cohort. The median operative duration was 60 min (interquartile range 45
85), with 17.7% of operations lasting longer than 90 min. Ten factors were found
to be significant independent predictors of operative durations > 90 min,
including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness
and CBD diameter. A risk score was then produced from these factors, and applied
to a cohort of 2405 patients from a tertiary centre for external validation. This
returned an area under the ROC curve of 0.708 (SE = 0.013, p < 0.001), with the
proportions of operations lasting > 90 min increasing more than eightfold from
5.1 to 41.8% in the extremes of the score. CONCLUSION: The scoring tool produced
in this study was found to be significantly predictive of long operative
durations on validation in an external cohort. As such, the tool may have the
potential to enable organisations to better organise theatre lists and deliver
greater efficiencies in care.
PMID- 29340841
TI - An efficient gene disruption method using a positive-negative split-selection
marker and Agrobacterium tumefaciens-mediated transformation for Nomuraea rileyi.
AB - Targeted gene disruption via Agrobacterium tumefaciens-mediated transformation
(ATMT) and homologous recombination is the most common method used to identify
and investigate the functions of genes in fungi. However, the gene disruption
efficiency of this method is low due to ectopic integration. In this study, a
high-efficiency gene disruption strategy based on ATMT and the split-marker
method was developed for use in Nomuraea rileyi. The beta-glucuronidase (gus)
gene was used as a negative selection marker to facilitate the screening of
putative transformants. We assessed the efficacy of this gene disruption method
using the NrCat1, NrCat4, and NrPex16 genes and found that the targeting
efficiency was between 36.2 and 60.7%, whereas the targeting efficiency using
linear cassettes was only 1.0-4.2%. The efficiency of negative selection assays
was between 64.1 and 82.3%. Randomly selected deletion mutants exhibited a single
copy of the hph cassette. Therefore, high-throughput gene disruption could be
possible using the split-marker method and the majority of ectopic integration
transformants can be eliminated using negative selection markers. This study
provides a platform to study the function of genes in N. rileyi.
PMID- 29340842
TI - Application of automated peritoneal dialysis in urgent-start peritoneal dialysis
patients during the break-in period.
AB - OBJECTIVE: Whether automated peritoneal dialysis (APD) is a feasible strategy for
urgent-start peritoneal dialysis (PD) therapy during the break-in period remains
unclear. This study was conducted to compare the efficacy as well as
complications among three PD modes during the break-in period. METHODS: Ninety
six patients treated with urgent-start PD after catheterization were
retrospectively analyzed. Patients were divided into three groups, incremental
continuous ambulatory PD (CAPD) group (n = 26); APD group (n = 42); and APD-CAPD
group (n = 28). Clinical parameters at the end of the break-in period and 1 month
after the initiation of PD treatment were collected and analyzed. RESULTS:
Compared with the traditional incremental CAPD, APD and APD-CAPD were superior as
they could effectively remove small-molecule uremic toxins and correct
electrolyte imbalance (P < 0.05), while did not increase the incidence of early
complications during the break-in period (P > 0.05). However, APD led to a
significant decline in albumin and pre-albumin, as compared with APD-CAPD and
CAPD (P < 0.05). A PD strategy consisting 6 days of APD and 3 days of CAPD showed
a great advantage in preventing excessive protein loss. There were no significant
differences in all tested biochemical parameters among the three groups at 1
month after treatment (all P > 0.05). CONCLUSION: Application of APD for urgent
start PD during the break-in period is feasible. A combination of APD and CAPD
regimens seems to be a more reasonable mode.
PMID- 29340843
TI - Phytoene production utilizing the isoprenoid biosynthesis capacity of
Thermococcus kodakarensis.
AB - Phytoene (C40H64) is an isoprenoid and a precursor of various carotenoids which
are of industrial value. Archaea can be considered to exhibit a relatively large
capacity to produce isoprenoids, as they are components of their membrane lipids.
Here, we aimed to produce isoprenoids such as phytoene in the hyperthermophilic
archaeon Thermococcus kodakarensis. T. kodakarensis harbors a prenyltransferase
gene involved in the biosynthesis of farnesyl pyrophosphate and geranylgeranyl
pyrophosphate, which are precursors of squalene and phytoene, respectively.
However, homologs of squalene synthase and phytoene synthase, which catalyze
their condensation reactions, are not found on the genome. Therefore, a
squalene/phytoene synthase homolog from an acidothermophilic archaeon Sulfolobus
acidocaldarius, Saci_1734, was introduced into the T. kodakarensis chromosome
under the control of a strong promoter. Production of the Saci_1734 protein was
confirmed in this strain, and the generation of phytoene was detected (0.08-0.75
mg L-1 medium). We then carried out genetic engineering in order to increase the
phytoene production yield. Disruption of an acetyl-CoA synthetase I gene involved
in hydrolyzing acetyl-CoA, the precursor of phytoene, together with the
introduction of a second copy of Saci_1734 led to a 3.4-fold enhancement in
phytoene production.
PMID- 29340844
TI - Comments on: insomnia, postpartum depression and estradiol in women after
delivery.
PMID- 29340845
TI - Dihydrotestosterone Treatment Accelerates Autograft Reversal Sciatic Nerve
Regeneration in Rats.
AB - Neuroactive steroids such as progesterone, testosterone, and their derivatives
have been widely studied for their neuroprotective roles in the nervous system.
Autologous nerve transplantation is considered as the gold standard repair
technique when primary suture is impossible; nevertheless, this method is far
from ideal. In this study, we aimed to explore the impact of dihydrotestosterone
(DHT), a 5alpha-reduced derivative of testosterone, on the recovery of peripheral
nerve injury treated with autologous nerve transplantation. Sprague-Dawley rats
were subjected to a 10-mm right side sciatic nerve reversed autologous nerve
transplantation and randomly divided into groups that received DHT or DHT +
flutamide (an androgen receptor blocker) daily for 8 weeks after operation. Our
results demonstrated that DHT could speed up the rate of axonal regeneration and
increase the expression of myelin protein zero (P0) in autograft reversal sciatic
nerves. Thus, our study provided new insights into improving the prognosis of
patients with long gap peripheral nerve defects.
PMID- 29340846
TI - Novel Isoforms of N16 and N19 Families Implicated for the Nacreous Layer
Formation in the Pearl Oyster Pinctada fucata.
AB - Although a wide variety of proteins and genes possibly related to the shell
formation in bivalve have been identified, their functions have been only
partially approved. We have recently performed deep sequencing of expressed
sequence tags (ESTs) from the pearl oyster Pinctada fucata using a next
generation sequencer, identifying a dozen of novel gene candidates which are
possibly associated with the nacreous layer formation. Among the ESTs, we focused
on three novel isoforms (N16-6, N16-7, and N19-2) of N16 and N19 families with
reference to five known genes in the families and determined the full-length cDNA
sequences of these isoforms. Reverse transcription-polymerase chain reaction
revealed that N16-6 was expressed in gill, gonad, adductor muscle, and mantle,
whereas N16-7 exclusively in mantle. N19-2 was expressed in all tissues examined.
In situ hybridization demonstrated their regional expression in mantle and pearl
sac, which well corresponded to those shown by EST analysis previously reported.
Shells in the pearl oyster injected with dsRNAs of N16-7 and N19-2 showed
abnormal surface appearance in the nacreous layer. Taken together, novel isoforms
in N16 and N19 families shown in this study are essential to form the nacreous
layer.
PMID- 29340847
TI - Comparative analysis of aneurysm volume by different methods based on angiography
and computed tomography angiography.
AB - Endovascular treatment and prognosis of intracranial aneurysms are based on size
and volume, which demand more accurate neuroimaging techniques. Aneurysm volume
calculation is important to choose endovascular treatment modalities and packing
density calculation. Of all these methods, it remains unknown which one is the
most accurate to calculate aneurysm volume. The objective of this study is to
compare the accuracy of three angiography-based versus three tomographic-based
methods which calculate aneurysm volume. A retrospective study which included
patients with ruptured and unruptured cerebral aneurysms diagnosed by angiogram
and computed tomography angiography (CTA) was done. The accuracy of each method
was assessed with an ellipsoid glass model of known volume, which helped us to
adjust variation in volumetric measurements done with AngioSuite(c) and
AngioCalc(c) softwares (based on angiographic and tomographic images), 3D
rotational angiography and 3D-CTA (tridimensional computed tomography
angiography), based on measurements of diameters such as maximal width and
maximal height. Descriptive statistics, ANOVA for repetitive samples and t test
were used. We included 89 patients (126 saccular intracraneal aneurysms).
AngioSuite(c) software (angiography-based) showed more accuracy compared to other
methods in our control model. The geometric system (AngioCalc) based on CTA
images was statistically different from all other methods studied. AngioCalc (CTA
based) demonstrated a significant difference compared with other methods hence,
it may overestimate volume measurements. AngioSuite
PMID- 29340848
TI - Validation of the Korean Munich Chronotype Questionnaire.
AB - PURPOSE: The Munich Chronotype Questionnaire (MCTQ) assesses actual sleep-wake
timing and has advantages compared to prior chronotype questionnaires in that it
differentiates sleep-wake patterns between work days and free days and uses
corrected mid-sleep time on free days after correcting for accumulated sleep debt
over the week to categorize chronotype. The current study, we validated the
Korean version of the MCTQ. METHODS: In this study, 310 participants (mean age =
27.09 +/- 5.64; 78.1% females) completed the Korean version of the MCTQ. RESULTS:
MCTQ parameters were significantly correlated with MEQ (Morningness-Eveningness
Questionnaire) scores (?r? >= 0.48), and test-retest reliability was >= 0.72.
Cutoff scores of 2.5%, which correlated to 2.36 and 8.57 mid-sleep times in our
sample, showed the best convergence with MEQ when categorizing chronotype.
CONCLUSIONS: Our study suggests that the MCTQ is a useful questionnaire in
assessing chronotype in young adults.
PMID- 29340849
TI - Risk factors associated with feline urolithiasis.
AB - Urinary tract diseases are among the main reasons for consultation in veterinary
clinics and hospitals. It affects animals of any age, breed and gender. Among the
diseases that affect this system, urolithiasis is the second largest cause of
clinical signs compatible with feline urinary tract disease. The term
urolithiasis refers to the presence of uroliths in any region of the urinary
tract, but it is more commonly seen in the bladder and urethra. Uroliths are
classified based on the type of mineral present in their composition, therefore,
quantitative and qualitative analyzes are important for a better therapeutic
approach. The animals may suffer from the disease and be asymptomatic, or show
nonspecific clinical signs, making the diagnosis difficult. The disease should
not be seen as a single problem, but as a consequence of various disorders. As
dietary, metabolic, genetic and infectious causes, as well as factors that
potentiate the chance of development of uroliths such as breed, age, sex, age
range, obesity, sedentary lifestyle, geographic region and climate. Thus, the
knowledge of the factors that influence the formation of uroliths, as well as the
understanding of the pathophysiology, are key elements for better alternatives of
therapy and prevention. The recognition of these factors helps to identify
susceptible populations, minimizing exposure and increasing the protection
factors, which facilitates the diagnosis and treatment of patients with
urolithiasis. The objective of this paper is to present the main risk factors
involved in the formation of urinary lithiasis in felines.
PMID- 29340850
TI - Drug-related problems among community-dwelling older adults in mainland China.
AB - Background Little is known about the extent of drug-related problems (DRPs) in
community-dwelling older adult patients with chronic diseases in mainland China.
Setting A medication therapy review service at a community health center in
Chongqing, China. Objective To identify and categorize DRPs along with
pharmacists' recommendations in addressing the DRPs identified. Method The study
was conducted between May 2015 and July 2016. A total of 102 community-dwelling
older adults were included. MTR was carried out by clinical pharmacists. DRPs and
pharmacotherapy recommendations were recorded and analyzed. Main outcome measure
The number of drug-related problems and main problem categories. Results The
average age of patients was 69.4 years. Patients took an average of 6.3
medications. A total of 489 DRPs were identified (mean of 4.8 per patient). The
most common category was under-treated (27.8%) followed by over- or under-dose
(18.8%) and monitoring (17.8%). The number of medications taken was the
significant associated factor for DRPs. Pharmacists made 526 recommendations to
address the DRPs (mean of 1.1 recommendations per DRP). Primary care providers
accepted 68.1% of these recommendations, and implemented 60.9% of them.
Conclusion The prevalence of DRPs among studied patient population was high.
Pharmacists may play a vital role in addressing the DRPs and optimize
pharmacotherapy through MTR service located in community health centers.
PMID- 29340851
TI - Comparison of antibiotic dosing recommendations for neonatal sepsis from
established reference sources.
AB - Background Incorrect dosing is the most frequent prescribing error in
neonatology, with antibiotics being the most frequently prescribed medicines.
Computer physician order entry and clinical decision support systems can create
consistency contributing to a reduction of medication errors. Although evidence
based dosing recommendations should be included in such systems, the evidence is
not always available and subsequently, dosing recommendations mentioned in
guidelines and textbooks are often based on expert opinion. Objective To compare
dosage recommendations for antibiotics in neonates with sepsis provided by eight
commonly used and well-established international reference sources. Setting An
expert team from our Dutch tertiary care neonatal intensive care unit selected
eight well-established international reference sources. Method Daily doses of the
seven most frequently used antibiotics in the treatment of neonatal sepsis,
classified by categories for birth weight and gestational age, were identified
from eight well-respected reference sources in neonatology/pediatric infectious
diseases. Main outcome measure Standardized average daily dosage. Results A
substantial variation in dosage recommendations of antibiotics for neonatal
sepsis between the reference sources was shown. Dosage recommendations of
ampicillin, ceftazidime, meropenem and vancomycin varied more than
recommendations for benzylpenicillin, cefotaxime and gentamicin. One reference
source showed a larger variation in dosage recommendations in comparison to the
average recommended daily dosage, compared to the other reference sources.
Conclusion Antibiotic dosage recommendations for neonates with sepsis can be
derived from important reference sources and guidelines. Further exploration to
overcome variation in dosage recommendations is necessary to obtain standardized
dosage regimens.
PMID- 29340852
TI - A geochemical view into continental palaeotemperatures of the end-Permian using
oxygen and hydrogen isotope composition of secondary silica in chert rubble
breccia: Kaibab Formation, Grand Canyon (USA).
AB - The upper carbonate member of the Kaibab Formation in northern Arizona (USA) was
subaerially exposed during the end Permian and contains fractured and zoned chert
rubble lag deposits typical of karst topography. The karst chert rubble has
secondary (authigenic) silica precipitates suitable for estimating continental
weathering temperatures during the end Permian karst event. New oxygen and
hydrogen isotope ratios of secondary silica precipitates in the residual rubble
breccia: (1) yield continental palaeotemperature estimates between 17 and 22
degrees C; and, (2) indicate that meteoric water played a role in the
crystallization history of the secondary silica. The continental
palaeotemperatures presented herein are broadly consistent with a global mean
temperature estimate of 18.2 degrees C for the latest Permian derived from
published climate system models. Few data sets are presently available that allow
even approximate quantitative estimates of regional continental
palaeotemperatures. These data provide a basis for better understanding the end
Permian palaeoclimate at a seasonally-tropical latitude along the western
shoreline of Pangaea.
PMID- 29340853
TI - Do bioresorbable polyesters have antimicrobial properties?
AB - Biodegradable and bioresorbable polyesters (BBPEs) are a widespread class of
aliphatic polymers with a plethora of applications in the medical field. Some
reports speculate that these polymers have intrinsic antibacterial activity as a
consequence of their acidic degradation by-products. The release of organic acids
as a result of the hydrolytic degradation of BBPEs in vivo and the resulting pH
drop could be an effective inhibitor of the growth of pathogens in the local
environment adjacent to BBPE-based devices. However, there is no clear and
conclusive evidence in the literature concerning the antibacterial activity of
BBPE to support or refute this hypothesis. In this communication we address this
point through an assessment of the antibacterial properties of six well
established commercially available BBPEs. Agar diffusion assays and optical
density measurements at 600 nm were performed on all the polymer samples to
characterize the growth of bacteria and any potential inhibition over an
incubation period of 24 h. The results indicated that BBPEs do not possess an
intrinsic and immediate antibacterial activity, which is consistent with the
clear mismatch between the time-scales for bacterial growth and the rate of
degradation of the polyesters.
PMID- 29340854
TI - Therapeutic efficacy and safety of a 1927-nm fractionated thulium laser on
pattern hair loss: an evaluator-blinded, split-scalp study.
AB - Laser- or light-assisted therapies have been used to improve the perifollicular
environment by upregulating the expression of growth factors and signaling
molecules for hair restoration. The aim of our study was to preclinically and
clinically evaluate the therapeutic efficacy and safety of a 1927-nm fractionated
thulium laser on pattern hair loss (PHL). An in vivo hairless mouse study and an
in vivo human skin environmental scanning electron microscopy (ESEM) study were
performed with different power and energy settings. Thereafter, an evaluator
blinded, split-scalp study was conducted to evaluate hair thickness and density
in 10 PHL patients treated with 12 sessions of fractionated thulium laser
treatment with or without post-laser treatment application of a growth factor
containing (GF) solution. In in vivo hairless mouse skin, inverted cone-shaped
zones of thulium laser-induced tissue coagulation (LITC) were noted immediately
after treatment in the epidermis and upper to mid-dermis without remarkable
ablative tissue injury. The ESEM study revealed round to oval-shaped zones of non
ablative LITC on the surface of the stratum corneum of a human subject
immediately after laser irradiation. In PHL patients, 12 sessions of thulium
laser monotherapy at 1-week intervals resulted in significantly increased hair
density and thickness. Post-laser treatment application of GF solution offered
additional therapeutic efficacy by improving hair density and thickness on the
split scalp. The use of a fractionated thulium laser with or without post-laser
therapy application of GF solution to treat PHL elicited remarkable improvements
in hair thickness and hair counts.
PMID- 29340855
TI - The relationship between target joints and direct resource use in severe
haemophilia.
AB - OBJECTIVES: Target joints are a common complication of severe haemophilia. While
factor replacement therapy constitutes the majority of costs in haemophilia, the
relationship between target joints and non drug-related direct costs (NDDCs) has
not been studied. METHODS: Data on haemophilia patients without inhibitors was
drawn from the 'Cost of Haemophilia across Europe - a Socioeconomic Survey'
(CHESS) study, a cost assessment in severe haemophilia A and B across five
European countries (France, Germany, Italy, Spain, and the United Kingdom) in
which 139 haemophilia specialists provided demographic and clinical information
for 1285 adult patients. NDDCs were calculated using publicly available cost
data, including 12-month ambulatory and secondary care activity: haematologist
and other specialist consultant consultations, medical tests and examinations,
bleed-related hospital admissions, and payments to professional care providers. A
generalized linear model was developed to investigate the relationship between
NDDCs and target joints (areas of chronic synovitis), adjusted for patient
covariates. RESULTS: Five hundred and thirteen patients (42% of the sample) had
no diagnosed target joints; a total of 1376 target joints (range 1-10) were
recorded in the remaining 714 patients. Mean adjusted NDDCs for persons with no
target joints were EUR 3134 (standard error (SE) EUR 158); for persons with one
or more target joints, mean adjusted NDDCs were EUR 3913 (SE EUR 157; average
mean effect EUR 779; p < 0.001). CONCLUSIONS: Our analysis suggests that the
presence of one or more target joints has a significant impact on NDDCs for
patients with severe haemophilia, ceteris paribus. Prevention and management of
target joints should be an important consideration of managing haemophilia
patients.
PMID- 29340856
TI - Core point-of-care ultrasound curriculum: What does every anesthesiologist need
to know?
AB - Point-of-care ultrasound (POCUS) is becoming an integral part of anesthesia
practice throughout the world. Despite the growing interest in POCUS among
trainees and faculty, POCUS training is variable among universities across
Canada. This suggests a need for curriculum development and standardization.
International guidelines for Emergency Medicine and Critical Care have common
frameworks and may be used as a reference to model anesthesia-specific curricula.
The Royal College of Anaesthetists of the United Kingdom currently offers the
only nationally approved POCUS curriculum for anesthesia and critical care
trainees. Most curricula have in common a stepwise approach that consists of
foundation of knowledge and skills and competency building through practice.
Nevertheless, a significant variety of didactic modalities have been described,
and online learning and simulation offer clear advantages. What constitutes the
minimum number of studies necessary to achieve competence is still debated as are
the most appropriate tools for assessment of POCUS competency.Availability of
trained staff anesthesiologists remains a major limitation to curricula
implementation in most centres. A National Curriculum should be modeled on the
Competency By Design Approach, in line with the CanMEDS 2015 roles, and start
with a focus on basic POCUS modalities and applications. Guidance for the
training and certification of POCUS among practicing anesthesiologists is
lacking.
PMID- 29340858
TI - Critical care echocardiography: a certification pathway for advanced users.
PMID- 29340859
TI - Comparative Proteomics of Chromium-Transformed Beas-2B Cells by 2D-DIGE and MALDI
TOF/TOF MS.
AB - Chromium (Cr) is a highly toxic, common heavy metal used in industrial
production. There are two types of Cr in nature: hexavalent chromium (Cr(VI)) and
chromium trichloride (Cr(III)). Cr(III) is involved in the metabolism of sugars
and lipids, whereas Cr(VI) is absorbed through the respiratory tract and skin and
generates free radicals that result in secondary toxicity. Cr(VI) leads to cancer
in the occupational population and is therefore recognized as a human carcinogen
by the International Agency for Research on Cancer. The specific mechanism
underlying Cr-induced carcinogenesis is complex. In this study, two-dimensional
fluorescence difference gel electrophoresis and matrix-assisted laser desorption
ionization-time-of-flight/time-of-flight mass spectrometry-based techniques were
performed to analyze differentially expressed proteins between Beas-2B human
bronchial epithelial cells and Cr(VI)-transformed Beas-2B cells. Many
differentially expressed proteins were identified in the cells after malignant
transformation, including serine/threonine kinase 11, endothelial nitric oxide
synthase 3, apolipoprotein A1, vinculin, and lamin A/C. These proteins are
involved in many signaling and metabolic pathways, including apoptosis,
autophagy, the PI3K/Akt signaling pathway, focal adhesion, cell motility, and
actin cytoskeleton rearrangement.
PMID- 29340860
TI - Trace element phytoextraction from contaminated soil: a case study under
Mediterranean climate.
AB - The current field study aims to assess the suitability of four different plant
species (i.e. poplar, willow, hemp and alfalfa) to be used for trace element (TE)
(i.e. Cd, Cu, Ni, Pb and Zn) phytoextraction under hot-arid Mediterranean climate
conditions. Plants were grown for two consecutive years on a moderate TE
contaminated soil, supplied with water and mineral nutrients. The growth and
physiological parameters were assessed throughout the trial to compare the
response of plants to the environmental pollution, and TE uptake rates were
measured for aboveground plant tissues. The phytoextraction rate for each species
was expressed as a function of aboveground biomass yield and the TE uptake and
translocation within the plant. Alfalfa played a significant role in reducing
extractable Ni (60.6%) and Zn (46%) in the soil, whereas hemp reduced 32% of
extractable Cd and 46% of extractable Pb; poplar decreased extractable Cd (37%),
Ni (49%), Pb (46%) and Zn (63%); and willow reduced the extractable Zn (73%)
compared to the beginning of the trial. No change in total TE content was
observed; however, poplar and willow were able to extract and accumulate the
highest amount of Zn (3200 and 5200 g ha-1 year-1 respectively) and Cu (182 and
116 g ha-1 year-1), whereas hemp, with 36 g ha-1 year-1, showed the best
phytoextraction potential for Pb. Overall, we found a positive correlation
between the phytoextraction rate and biomass yield, extractable TE concentration
and translocation factor (TF) and a negative relationship with Ca concentration
in the soil.
PMID- 29340861
TI - Investigating the composition characteristics of dissolved and
particulate/colloidal organic matter in effluent-dominated stream using
fluorescence spectroscopy combined with multivariable analysis.
AB - Fluorescence excitation-emission matrix (EEM) spectroscopy combined with
principal component analysis (PCA) and parallel factor analysis (PARAFAC) were
used to investigate the compositional characteristics of dissolved and
particulate/colloidal organic matter and its correlations with nitrogen,
phosphorus, and heavy metals in an effluent-dominated stream, Northern China. The
results showed that dissolved organic matter (DOM) was comprised of fulvic-like,
humic-like, and protein-like components in the water samples, and fulvic-like
substances were the main fraction of DOM among them. Particulate/colloidal
organic matter (PcOM) consisted of fulvic-like and protein-like matter. Fulvic
like substances existed in the larger molecular form in PcOM, and they comprised
a large amount of nitrogen and polar functional groups. On the other hand,
protein-like components in PcOM were low in benzene ring and bound to heavy
metals. It could be concluded that nitrogen, phosphorus, and heavy metals in
effluent had an effect on the compositional characteristics of natural DOM and
PcOM, which may deepen our understanding about the environmental behaviors of
organic matter in effluent.
PMID- 29340862
TI - Effect of brewery wastewater obtained from different phases of treatment plant on
seed germination of chickpea (Cicer arietinum), maize (Zea mays), and pigeon pea
(Cajanus cajan).
AB - Brewing industry releases large quantities of wastewater after product
generation. Brewery wastewater contains organic compounds which are biodegradable
in nature. These biodegradable wastes can be recycled and reused and hence
considered as suitable products for agriculture. But before using wastewater for
agriculture, it is better to evaluate the phytotoxic effects of wastewater on
crops. Hence, the main objective of this study is to evaluate the effects of
brewery effluent on seed germination and growth parameters of selected crop
species like chickpea (Cicer arietinum), maize (Zea mays), and pigeon pea
(Cajanus cajan). Study comprised seven types of water treatments-tap water as
control, diluted UASBR effluent (50% effluent + 50% distilled water): UASBR50,
undiluted UASBR effluent: UASBR100, diluted TC effluent (50% effluent + 50%
distilled water): ETP50,TC effluent without dilution: ETP100, 10% diluted reverse
osmosis (RO10) reject (10% RO reject + 90% distilled water), and 25% diluted
reverse osmosis(RO25) reject (25% RO reject + 75% distilled water) with three
replications in completely randomized design. Germination test was performed in
petri plates for 5 days. Parameters like germination percentage, germination rate
index, seedling length, phytotoxicity index, seed vigor index, and biomass were
calculated. All parameters decreased with increase in respective effluent
concentration. Among all treatments, RO25 showed highest inhibitory effect on all
three crops. Even though undiluted effluent of UASBR and ETP effluent showed
positive effect on germination, seedling growth of three crops was promoted to
the maximum by UASBR50 and ETP50. Hence, from the study, it was concluded that
dilution of brewery effluent can be recommended before using it for irrigational
purpose.
PMID- 29340863
TI - Effects of urease and nitrification inhibitors on the soil mineral nitrogen
dynamics and nitrous oxide (N2O) emissions on calcareous soil.
AB - Urease inhibitors and nitrification inhibitors can reduce nitrogen (N) loss in
agriculture soil. However, the effect of inhibitors on soil N2O emissions under
the drip irrigation system remains unclear. A pot and a field experiment with two
inhibitors were conducted to explore how inhibitors regulate soil nitrogen
transformation and N2O emissions. In the pot experiment, three treatments
included control, urea, and urea + N-(n-butyl)thiophosphoric triamide (NBPT,
urease inhibitor). In the field experiment, three treatments included control,
urea, and urea + NBPT + 2-chloro-6-(trichloromethyl)pyridine (nitrapyrin,
nitrification inhibitor). The urease inhibition rate in the treatment of urea +
NBPT was 27.5% at the 14th day of incubation (pot experiment), and NH4+-N was
significantly decreased by 37-64% compared with urea alone treatment. In the
field experiment, the nitrification inhibition rate in the treatment of urea +
NBPT + nitrapyrin was 47.7 and 63.9% on the 3rd day after fertilization at the
wheat heading and filling stages, respectively. Compared to urea treatment, NO3-
N concentration in the double-inhibitor-added treatment was significantly
decreased by 32 and 20% on the 5th day after fertilization at the heading and
filling stages, respectively; N2O fluxes were also decreased by 30.9 and 33.3% at
the two stages of wheat, respectively. In total, adding an inhibitor reduced N
loss by 7.39 and 7.44% at the 14th and 35th day in the pot experiment and by
10.53 and 6.65% at the two growing stages of wheat in the field experiment,
respectively. Path and correlation analysis showed that N2O emissions were
significantly correlated with soil NO3- in both pot and field experiments.
PMID- 29340864
TI - Analysis of accumulation formation of sediment contamination in reservoirs after
decades of running: a case study of nitrogen accumulation in Biliuhe Reservoir.
AB - Sediment contamination is an important influencing factor for reservoir water
quality. Investigations have shown that reservoirs are facing the risk of
sediment contamination after running for several decades in China. This paper
proposes that the accumulation of sediment contaminant is resulted from the
difference between the input and output of contaminant. Further, an accumulation
model of reservoir sediment nitrogen is established based on this theory. The
calculation result of Biliuhe Reservoir shows that inflow rate of total nitrogen
into the reservoir is 4521.47 t/a, the outflow rate is 1033.97 t/a, nitrogen
removal by denitrification is 1465.81 t/a, and the accumulation rate is 1841.68
t/a. The accumulation rate of total nitrogen is 77.84 t/a in water, 924.42 t/a in
suspended solids, and 839.42 t/a in sediment. The accumulation of nitrogen
resulted in the total nitrogen concentration in water increasing from 1.71 mg/L
in 1995 to 3.78 mg/L in 2013, and that in sediment increasing from 779.10 mg/kg
in 1993 to 2725.00 mg/kg in 2013. It is concluded that sediment contamination has
the characteristics of significant accumulation trend, complex forms, and high
security risks, which has been a hidden security risk for reservoirs after
decades of running. Heterogeneity of the reservoir and complicated influencing
factors of sediment contaminant accumulation should be concerned next.
PMID- 29340865
TI - Design of a tripartite network for the prediction of drug targets.
AB - Drug-target networks have aided in many target prediction studies aiming at drug
repurposing or the analysis of side effects. Conventional drug-target networks
are bipartite. They contain two different types of nodes representing drugs and
targets, respectively, and edges indicating pairwise drug-target interactions. In
this work, we introduce a tripartite network consisting of drugs, other bioactive
compounds, and targets from different sources. On the basis of analog
relationships captured in the network and so-called neighbor targets of drugs,
new drug targets can be inferred. The tripartite network was found to have a
stable structure and simulated network growth was accompanied by a steady
increase in assortativity, reflecting increasing correlation between degrees of
connected nodes leading to even network connectivity. Local drug environments in
the tripartite network typically contained neighbor targets and revealed
interesting drug-compound-target relationships for further analysis. Candidate
targets were prioritized. The tripartite network design extends standard drug
target networks and provides additional opportunities for drug target prediction.
PMID- 29340866
TI - "In silico" study of the binding of two novel antagonists to the nociceptin
receptor.
AB - Antagonists of the nociceptin receptor (NOP) are raising interest for their
possible clinical use as antidepressant drugs. Recently, the structure of NOP in
complex with some piperidine-based antagonists has been revealed by X-ray
crystallography. In this study, a multi-flexible docking (MF-docking) procedure,
i.e. docking to multiple receptor conformations extracted by preliminary
molecular dynamics trajectories, together with hybrid quantum mechanics/molecular
mechanics (QM/MM) simulations have been carried out to provide the binding mode
of two novel NOP antagonists, one of them selective (BTRX-246040, formerly named
LY-2940094) and one non selective (AT-076), i.e. able to inactivate NOP as well
as the classical u- k- and delta-opioid receptors (MOP KOP and DOP). According to
our results, the pivotal role of residue D1303,32 (upper indexes are Ballesteros
Weinstein notations) is analogous to that enlighten by the already known X-ray
structures of opioid receptors: binding of the molecules are predicted to require
a slight readjustment of the hydrophobic pocket (residues Y1313,33, M1343,36,
I2195,43, Q2806,52 and V2836,55) in the orthosteric site of NOP, accommodating
either the pyridine-pyrazole (BTRX-246040) or the isoquinoline (AT-076) moiety of
the ligand, in turn allowing the protonated piperidine nitrogen to maximize
interaction (salt-bridge) with residue D1303,32 of the NOP, and the aromatic head
to be sandwiched in optimal pi-stacking between Y1313,33 and M1343,36. The QM/MM
optimization after the MF-docking procedure has provided the more likely
conformations for the binding to the NOP receptor of BTRX-246040 and AT-076,
based on different pharmacophores and exhibiting different selectivity profiles.
While the high selectivity for NOP of BTRX-246040 can be explained by
interactions with NOP specific residues, the lack of selectivity of AT-076 could
be associated to its ability to penetrate into the deep hydrophobic pocket of
NOP, while retaining a conformation very similar to the one assumed by the
antagonist JDTic into the K-opioid receptor. The proposed binding geometries fit
better the binding pocket environment providing clues for experimental studies
aimed to design selective or multifunctional opioid drugs.
PMID- 29340867
TI - Photoluminescent and Thermoluminescent Studies of Dy3+ and Eu3+ Doped Y2O3
Phosphors.
AB - Eu3+ doped and Dy3+ codoped yttrium oxide (Y2O3) phosphors have been prepared
using solid-state reaction technique (SSR). The prepared phosphors were
characterized by X-ray diffractometer (XRD), energy dispersive X-ray (EDX)
spectroscopy, scanning electron microscopy (SEM) and Fourier transforms infrared
spectroscopy (FTIR) techniques. Photoluminescence (PL) and Thermoluminescence
(TL) properties were studied in detail. PL emission spectra were recorded for
prepared phosphors under excitation wavelength 254 nm, which show a high intense
peak at 613 nm for Y2O3:Dy3+, Eu3+ (1:1.5 mol %) phosphor. The correlated color
temperature (CCT) and CIE analysis have been performed for the synthesized
phosphors. TL glow curves were recorded for Eu3+doped and Dy3+codoped phosphors
to study the heating rate effect and dose response. The kinetic parameters were
calculated using peak shape method for UV and gamma exposures through
computerized glow curve deconvolution (CGCD) technique. The phosphors show second
order kinetics and activation energies varying from 5.823 * 10- 1 to 18.608 * 10-
1 eV.
PMID- 29340868
TI - Recent Progress in Understanding the Mechanisms of Pain and Itch: the Second
Special Issue.
PMID- 29340870
TI - A Pilot Evaluation of the Rapid Response Program: A Home Based Family Therapy.
AB - A pilot evaluation study of the implementation of the Rapid Response Program, a
program utilizing the ecosystemic structural family therapy model, in a rural
area of Pennsylvania was conducted. This approach was implemented in children's
mental health to supplant a costly model of care that had not proven to break the
cycle of dependency for children with severe behavioral problems and their
families. Initial results show that the Rapid Response Program appears to improve
problematic family patterns and children's behavioral problems. The study results
are limited by small sample size; however, the outcomes suggest that the program
warrants further study using a more rigorous research design with a larger
sample.
PMID- 29340869
TI - Intervention Effect of Repetitive TMS on Behavioral Adjustment After Error
Commission in Long-Term Methamphetamine Addicts: Evidence From a Two-Choice
Oddball Task.
AB - Behavioral adjustment plays an important role in the treatment and relapse of
drug addiction. Nonetheless, few studies have examined behavioral adjustment and
its plasticity following error commission in methamphetamine (METH) dependence,
which is detrimental to human health. Thus, we investigated the behavioral
adjustment performance following error commission in long-term METH addicts and
how it varied with the application of repetitive transcranial magnetic
stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC). Twenty
nine male long-term METH addicts (for > 3 years) were randomly assigned to high
frequency (10 Hz, n = 15) or sham (n = 14) rTMS of the left DLPFC during a two
choice oddball task. Twenty-six age-matched, healthy male adults participated in
the two-choice oddball task pretest to establish normal performance for
comparison. The results showed that 10 Hz rTMS over the left DLPFC significantly
decreased the post-error slowing effect in response times of METH addicts. In
addition, the 10 Hz rTMS intervention remarkably reduced the reaction times
during post-error trials but not post-correct trials. While the 10 Hz rTMS group
showed a more pronounced post-error slowing effect than the healthy participants
during the pretest, the post-error slowing effect in the posttest of this sample
was similar to that in the healthy participants. These results suggest that high
frequency rTMS over the left DLPFC is a useful protocol for the improvement of
behavioral adjustment after error commission in long-term METH addicts.
PMID- 29340871
TI - Neurotoxicity of Prosopis juliflora: from Natural Poisoning to Mechanism of
Action of Its Piperidine Alkaloids.
AB - Prosopis juliflora was introduced in northeastern Brazil in the 1940s, and since
then, it has been available as an alternative for animal nutrition. However, the
consumption of P. juliflora as main or sole source of food causes an illness in
animals known locally as "cara torta" disease. Cattle and goats experimentally
intoxicated presents neurotoxic damage in the central nervous system. Histologic
lesions were mainly characterized by vacuolation and loss of neurons in
trigeminal motor nuclei. Furthermore, mitochondrial damage in neurons and gliosis
was reported in trigeminal nuclei of intoxicated cattle. Studies, using neural
cell cultures, have reproduced the main cellular alterations visualized in cara
torta disease and contributed to understanding the mechanism of action piperidine
alkaloids, the main neurotoxic compound in P. juliflora leaves and pods. Here, we
will present aspects of the biological and toxicological properties of P.
juliflora and its pharmacologically active compounds.
PMID- 29340872
TI - Abstracts of the 2017 A-CURE Symposium.
PMID- 29340874
TI - Lattice Boltzmann simulations of droplet dynamics in time-dependent flows.
AB - We study the deformation and dynamics of droplets in time-dependent flows using
3D numerical simulations of two immiscible fluids based on the lattice Boltzmann
model (LBM). Analytical models are available in the literature, which assume the
droplet shape to be an ellipsoid at all times (P.L. Maffettone, M. Minale, J. Non
Newton. Fluid Mech 78, 227 (1998); M. Minale, Rheol. Acta 47, 667 (2008)). Beyond
the practical importance of using a mesoscale simulation to assess "ab initio"
the robustness and limitations of such theoretical models, our simulations are
also key to discuss --in controlled situations-- some relevant phenomenology
related to the interplay between the flow time scales and the droplet time scales
regarding the "transparency" transition for high enough shear frequencies for an
external oscillating flow. This work may be regarded as a step forward to discuss
extensions towards a novel DNS approach, describing the mesoscale physics of
small droplets subjected to a generic hydrodynamical strain field, possibly
mimicking the effect of a realistic turbulent flow on dilute droplet suspensions.
PMID- 29340873
TI - Fontan Surgical Planning: Previous Accomplishments, Current Challenges, and
Future Directions.
AB - The ultimate goal of Fontan surgical planning is to provide additional insights
into the clinical decision-making process. In its current state, surgical
planning offers an accurate hemodynamic assessment of the pre-operative
condition, provides anatomical constraints for potential surgical options, and
produces decent post-operative predictions if boundary conditions are similar
enough between the pre-operative and post-operative states. Moving forward,
validation with post-operative data is a necessary step in order to assess the
accuracy of surgical planning and determine which methodological improvements are
needed. Future efforts to automate the surgical planning process will reduce the
individual expertise needed and encourage use in the clinic by clinicians. As
post-operative physiologic predictions improve, Fontan surgical planning will
become an more effective tool to accurately model patient-specific hemodynamics.
PMID- 29340875
TI - Thromboelastography-based anticoagulation management during extracorporeal
membrane oxygenation: a safety and feasibility pilot study.
AB - BACKGROUND: There is no consensus on the management of anticoagulation during
extracorporeal membrane oxygenation (ECMO). ECMO is currently burdened by a high
rate of hemostatic complications, possibly associated with inadequate monitoring
of heparin anticoagulation. This study aims to assess the safety and feasibility
of an anticoagulation protocol for patients undergoing ECMO based on
thromboelastography (TEG) as opposed to an activated partial thromboplastin time
(aPTT)-based protocol. METHODS: We performed a multicenter, randomized,
controlled trial in two academic tertiary care centers. Adult patients with acute
respiratory failure treated with veno-venous ECMO were randomized to manage
heparin anticoagulation using a TEG-based protocol (target 16-24 min of the R
parameter, TEG group) or a standard of care aPTT-based protocol (target 1.5-2 of
aPTT ratio, aPTT group). Primary outcomes were safety and feasibility of the
study protocol. RESULTS: Forty-two patients were enrolled: 21 were randomized to
the TEG group and 21 to the aPTT group. Duration of ECMO was similar in the two
groups (9 (7-16) days in the TEG group and 11 (4-17) days in the aPTT group, p =
0.74). Heparin dosing was lower in the TEG group compared to the aPTT group (11.7
(9.5-15.3) IU/kg/h vs. 15.7 (10.9-21.3) IU/kg/h, respectively, p = 0.03). Safety
parameters, assessed as number of hemorrhagic or thrombotic events and
transfusions given, were not different between the two study groups. As for the
feasibility, the TEG-based protocol triggered heparin infusion rate adjustments
more frequently (p < 0.01) and results were less frequently in the target range
compared to the aPTT-based protocol (p < 0.001). Number of prescribed TEG or aPTT
controls (according to study groups) and protocol violations were not different
between the study groups. CONCLUSIONS: TEG seems to be safely used to guide
anticoagulation management during ECMO. Its use was associated with the
administration of lower heparin doses compared to a standard of care aPTT-based
protocol. Trial registration ClinicalTrials.gov, October 22,2014. Identifier:
NCT02271126.
PMID- 29340876
TI - Biomaterials and Regenerative Medicine in Urology.
AB - Autologous gastrointestinal tissue is the gold standard biomaterial for urinary
tract reconstruction despite its long-term neuromechanical and metabolic
complications. Regenerative biomaterials have been proposed as alternatives;
however many are limited by a poor host derived regenerative response and
deficient supportive elements for effective tissue regeneration in vivo.
Urological biomaterials are sub-classified into xenogenic extracellular matrices
(ECMs) or synthetic polymers. ECMs are decellularised, biocompatible,
biodegradable biomaterials derived from animal organs. Synthetic polymers vary in
chemical composition but may have the benefit of being reliably reproducible from
a manufacturing perspective. Urological biomaterials can be 'seeded' with
regenerative stem cells in vitro to create composite biomaterials for grafting in
vivo. Mesenchymal stem cells are advantageous for regenerative purposes as they
self-renew, have long-term viability and possess multilineage differentiation
potential. Currently, tissue-engineered biomaterials are developing rapidly in
regenerative urology with many important clinical milestones achieved. To truly
translate from bench to bedside, regenerative biomaterials need to provide better
clinical outcomes than current urological tissue replacement strategies.
PMID- 29340877
TI - Brief Report: Subjective Social Mobility and Depressive Symptoms in Syrian
Refugees to Germany.
AB - Previous findings indicate that refugees are at increased risk for mental health
problems. In addition to stressful pre-migration experiences, post-migration
factors may contribute to poor mental health outcomes. Among immigrants to the
United States, downward mobility in subjective social status (SSS) was associated
with depression, corroborating the potentially detrimental mental health
consequences of a decline in one's perceived social position. The present study
examined whether downward mobility in SSS among male refugees from Syria to
Germany is associated with depression. We found that refugees who experience
stronger downward mobility in SSS exhibit more severe depressive symptoms and
were more likely to fulfill provisional DSM-IV criteria for a diagnosis of Major
Depression. Our findings highlight the importance to consider the 'social pain'
of downward social mobility during the post-migration phase.
PMID- 29340878
TI - Core curriculum case illustration: tubo-ovarian abscess.
AB - This is the 47th installment of a series that will highlight one case per
publication issue from the bank of cases available online as part of the American
Society of Emergency Radiology (ASER) educational resources. Our goal is to
generate more interest in and use of our online materials. To view more cases
online, please visit the ASER Core Curriculum and Recommendations for Study
online at: http://www.erad.org/page/CCIP_TOC .
PMID- 29340880
TI - GATA-3 is superior to GCDFP-15 and mammaglobin to identify primary and metastatic
breast cancer.
AB - PURPOSE: Despite numerous studies on the utility of GATA-3 as breast cancer
marker, its comparison with other breast markers, its concordance between primary
and metastatic tumors and its expression in primary cancers from sites with
frequent breast metastases remains unclear. METHODS: To address these questions,
totally 993 invasive breast cancers (IBC), 254 paired nodal metastases, 23
distant metastases, and 208 lung carcinomas were included. GATA-3 expression was
analyzed by immunohistochemistry and compared to other breast markers [gross
cystic disease fluid protein 15 (GCDFP-15) and mammaglobin (MGB)]. RESULTS: GATA
3 was expressed in 82.5% of IBC, predominantly in luminal (93.9%), and lower in
non-luminal cancers [59.6% of HER2 overexpressing (HER2-OE) and 38.1% of triple
negative breast cancer (TNBC) subtypes]. GATA-3 identified more IBC than GCDFP-15
(23.9%) and MGB (46.6%). However, MGB showed a comparable sensitivity for non
luminal cancers to GATA-3. Combining MGB and GATA-3 improved sensitivity for both
HER2-OE (80.8%) and TNBC cases (55.4%). GATA-3 showed a high sensitivity for
nodal metastases and distant metastases, with good concordance with primary
tumors. GATA-3 was expressed in 1.0% of lung carcinomas, with sensitivity and
specificity of 82.5 and 99.0% in differentiating IBC and lung carcinoma.
CONCLUSIONS: GATA-3 expression was the highest in luminal breast carcinomas, and
showed higher sensitivity than GCDFP-15 and MGB. However, in the poorly
differentiated IBC, its utility was still limited. One should be aware of the
possible GATA-3 expression in lung carcinomas.
PMID- 29340879
TI - Diethylstilbestrol arrested spermatogenesis and somatic growth in the juveniles
of yellow catfish (Pelteobagrus fulvidraco), a fish with sexual dimorphic growth.
AB - In fish, spermatogenesis and somatic growth are mainly regulated by hypothalamic
pituitary-gonadal (HPG) and hypothalamic-pituitary-somatic (HPS) axes,
respectively. Xenoestrogens have been reported to impair spermatogenesis in some
fishes, and arrest somatic growth in some others, whereas, whether xenoestrogens
are capable of disrupting spermatogenesis and somatic growth simultaneously in
fish that exhibits sexual dimorphic growth is little known, and the underlying
mechanisms remain poorly understood. In this study, male juveniles of yellow
catfish (Pelteobagrus fulvidraco), which exhibits a sexual dimorphic growth that
favors males, were exposed to diethylstilbestrol (DES) for 28 days. After
exposure, DES significantly disrupted the spermatogenesis (decreased gonadal
somatic index (GSI) and germ cell number) and arrested the somatic growth
(declined body weight) of the catfish juveniles. Gene expression and plasma
steroid analyses demonstrated the suppressed mRNA levels of genes in HPG axis
(gnrh-II, fshbeta, and lhbeta in the brain and dmrt1, sf1, fshr, cyp17a1,
cyp19a1a, and cyp11b2 in the testis) and decreased 17beta-estrodial (E2) and 11
ketotestosterone (11-KT) levels in plasma. Further analysis revealed the arrested
germ cell proliferation (cyclin d1), meiosis (dmc1, sycp3), and enhanced
apoptosis (decreased bcl-2 and elevated bax/bcl-2 ratio) in the testis. Besides,
DES also suppressed the mRNA levels of genes in HPS axis (ghrh, gh, and prl in
the brain and ghr, igf1, igf2a, and igf2b in the liver). The suppressed HPG and
HPS axes were thus supposed to disturb spermatogenesis and arrest somatic growth
in yellow catfish. The present study greatly extended our understanding on the
mechanisms underlying the toxicity of DES on spermatogenesis and somatic growth
of fish.
PMID- 29340881
TI - Circulating free DNA integrity and concentration as independent prognostic
markers in metastatic breast cancer.
AB - PURPOSE: Non-invasive blood-based molecular markers have been investigated for
cancer diagnosis and prognosis. Circulating free or cell-free DNA (cfDNA)
variables have been shown to be putative markers in breast cancer prognosis.
METHODS: Here, we investigated the potential prognostic ability of cfDNA
concentration and cfDNA integrity (cfDI) in a study cohort of 268 patients by
quantitative PCR. We compared cfDNA concentration and cfDI at baseline and after
one cycle of therapy in metastatic breast cancer (MBC) patients. RESULTS: A
significantly increased cfDI (P = 1.21E-7 for ALU and P = 1.87E-3 for LINE1) and
decreased cfDNA concentration (P = 1.17E-3 for ALU and P = 1.60E-2 for LINE1) in
both repetitive DNA elements after one cycle of therapy was observed. A multiple
Cox regression model indicated that cfDI and cfDNA concentration can serve as
independent prognostic markers in patients at baseline with HR (95% CI) of 0.70
(0.48-1.01) for ALU cfDI, 0.63 (0.44-0.92) for LINE1 cfDI, 2.44 (1.68-3.53) for
ALU cfDNA concentration, and 2.12 (1.47-3.06) for LINE1 cfDNA concentration and
after one cycle of therapy with HR (95% CI) of 0.59 (0.42-0.84) for ALU cfDI,
0.51 (0.36-0.74) for LINE1 cfDI, 1.59 (1.31-1.92) for ALU cfDNA concentration,
and 1.30 (1.17-1.45) for LINE1 cfDNA concentration, respectively. By comparing
integrated prediction error of different models, cfDNA variables were shown to
improve the prognostic power of the CTC status. CONCLUSIONS: We hereby show that
cfDNA variables, especially in combination with other markers, can serve as
attractive prognostic markers for MBC patients at baseline and during the
systematic therapy.
PMID- 29340882
TI - Circulating small-sized endothelial microparticles as predictors of clinical
outcome after chemotherapy for breast cancer: an exploratory analysis.
AB - PURPOSE: Therapeutic exploitation of angiogenesis in breast cancer has been
limited by the lack of reliable biomarkers. Circulating small-sized endothelial
microparticles (sEMP) are likely to play a significant role as messengers of
angiogenesis. Higher levels of EMP have been observed in cancer patients, but
their prognostic value in breast cancer is unknown. Our aim was to determine the
value of circulating sEMP as a marker of response to chemotherapy in breast
cancer. METHODS: We included patients with breast cancer treated with neoadjuvant
or first-line chemotherapy. Baseline and post-treatment circulating sEMP (CD144+)
were quantified using a flow cytometer approach specifically designed for
analysis of small-sized particles (0.1-0.5 MUm). Small-sized EMP response was
defined as a post-treatment decrease of sEMP larger than the median decrease of
sEMP after chemotherapy. Baseline and post-chemotherapy VEGFA levels were
determined with ELISA. RESULTS: Forty-four breast cancer patients were included
(19 with metastatic and 25 with locally advanced disease). Median levels of sEMP
decreased after chemotherapy (P = 0.005). Response to chemotherapy showed a non
significant trend to associate with sEMP response (P = 0.056). A sEMP response
was observed in 51% of patients and was associated with better overall survival
(HR 0.18; 95% CI 0.04-0.87; P = 0.02) and progression free survival (HR 0.30; 95%
CI 0.09-0.99; P = 0.04) in the group of women with metastatic disease. Post
chemotherapy decrease of VEGFA levels was not associated with breast cancer
prognosis. CONCLUSIONS: Our results did not support sEMP as a marker of response
to chemotherapy. However, our exploratory analysis suggests that in patients with
metastatic breast cancer, the decrease of sEMP levels after chemotherapy is
associated with better overall and disease free survival and might be superior to
VEGFA levels as an angiogenesis-related prognostic marker.
PMID- 29340883
TI - Associations of coffee consumption and caffeine intake with mammographic breast
density.
AB - PURPOSE: Previous studies suggest that coffee and caffeine intake may be
associated with reduced breast cancer risk. We investigated the association of
coffee and caffeine intake with mammographic breast density by woman's menopausal
status and, in postmenopausal women, by hormone therapy (HT). METHODS: This study
included 4130 cancer-free women within the Nurses' Health Study and Nurses'
Health Study II cohorts. Percent breast density (PD) was measured from digitized
film mammograms using a computer-assisted thresholding technique and square root
transformed for the analysis. Average cumulative coffee/caffeine consumption was
calculated using data from all food frequency questionnaires preceding the
mammogram date. Information regarding breast cancer risk factors was obtained
from questionnaires closest to the mammogram date. We used generalized linear
regression to quantify associations of regular, decaffeinated, and total coffee,
and energy-adjusted caffeine intake with percent density. RESULTS: In
multivariable analyses, decaffeinated coffee was positively associated with PD in
premenopausal women (2+ cups/day: beta = 0.23, p trend = 0.03). In postmenopausal
women, decaffeinated and total coffee were inversely associated with PD
(decaffeinated 2+ cups/day: beta = - 0.24, p trend = 0.04; total 4+ cups/day:
beta = - 0.16, p trend = 0.02). Interaction of decaffeinated coffee with
menopausal status was significant (p-interaction < 0.001). Among current HT
users, regular coffee and caffeine were inversely associated with PD (regular
coffee 4+ cups/day: beta = - 0.29, p trend = 0.01; caffeine 4th vs. 1st quartile:
beta = - 0.32, p trend = 0.01). Among past users, decaffeinated coffee was
inversely associated with PD (2+ cups/day beta = - 0.70, p trend = 0.02).
CONCLUSIONS: Associations of decaffeinated coffee with percent density differ by
woman's menopausal status. Associations of regular coffee and caffeine with
percent density may differ by HT status.
PMID- 29340884
TI - "I would like to discuss it further with an expert": a focus group study of
Finnish adults' perspectives on genetic secondary findings.
AB - Lowered costs of genomic sequencing facilitate analyzing large segments of
genetic data. Ethical debate has focused on whether and what kind of incidental
or secondary findings (SFs) to report, and how to obtain valid informed consent.
However, people's support needs after receiving SFs have received less attention.
We explored Finnish adults' perspectives on reporting genetic SFs. In this
qualitative study which included four focus group discussions (N = 23) we used
four vignette letters, each reporting a genetic SF predisposing to a different
disease: familial hypercholesterolemia, long QT syndrome, Lynch syndrome, and Li
Fraumeni syndrome. Transcribed focus group discussions were analyzed using
inductive thematic analysis. Major themes were immediate shock, dealing with
worry and heightened risk, fear of being left alone to deal with SFs, disclosing
to family, and identified support needs. Despite their willingness to receive
SFs, participants were concerned about being left alone to deal with them.
Empathetic expert support and timely access to preventive care were seen as
essential to coping with shock and worry, and disclosing SFs to family.
Discussion around SFs needs to concern not only which findings to report, but
also how healthcare systems need to prepare for providing timely access to
preventive care and support for individuals and families.
PMID- 29340885
TI - Quantifying Diastolic Function: From E-Waves as Triangles to Physiologic Contours
via the 'Geometric Method'.
AB - Conventional echocardiographic diastolic function (DF) assessment approximates
transmitral flow velocity contours (Doppler E-waves) as triangles, with peak
(Epeak), acceleration time (AT), and deceleration time (DT) as indexes. These
metrics have limited value because they are unable to characterize the underlying
physiology. The parametrized diastolic filling (PDF) formalism provides a
physiologic, kinematic mechanism based characterization of DF by extracting
chamber stiffness (k), relaxation (c), and load (x o ) from E-wave contours. We
derive the mathematical relationship between the PDF parameters and Epeak, AT, DT
and thereby introduce the geometric method (GM) that computes the PDF parameters
using Epeak, AT, and DT as input. Numerical experiments validated GM by analysis
of 208 E-waves from 31 datasets spanning the full range of clinical diastolic
function. GM yielded indistinguishable average parameter values per subject vs.
the gold-standard PDF method (k: R2 = 0.94, c: R2 = 0.95, x o : R2 = 0.95, p <
0.01 all parameters). Additionally, inter-rater reliability for GM-determined
parameters was excellent (k: ICC = 0.956 c: ICC = 0.944, x o : ICC = 0.993).
Results indicate that E-wave symmetry (AT/DT) may comprise a new index of DF. By
employing indexes (Epeak, AT, DT) that are already in standard clinical use the
GM capitalizes on the power of the PDF method to quantify DF in terms of
physiologic chamber properties.
PMID- 29340886
TI - Use of Kerrison Rongeur for safe and effective removal of bone in
temporomandibular joint ankylosis.
PMID- 29340888
TI - Wet Cupping Therapy Improves Local Blood Perfusion and Analgesic Effects in
Patients with Nerve-Root Type Cervical Spondylosis.
AB - OBJECTIVE: To observe wet cupping therapy (WCT) on local blood perfusion and
analgesic effects in patients with nerve-root type cervical spondylosis (NT-CS).
METHODS: Fifty-seven NT-CS patients were randomly divided into WCT group and
Jiaji acupoint-acupuncture (JA) group according a random number table. WCT group
(30 cases) was treated with WCT for 10 min, and JA group (27 cases) was treated
with acupuncture for 10 min. The treatment efficacies were evaluated with a
Visual Analogue Scale (VAS). Blood perfusion at Dazhui (GV 14) and Jianjing (GB
21) acupoints (affected side) was observed with a laser speckle flowmetry, and
its variations before and after treatment in both groups were compared as well.
RESULTS: In both groups, the VAS scores significantly decreased after the
intervention (P<0.01), while the blood perfusion at the two acupoints
significantly increased after intervention (P<0.05); however, the increasement
magnitude caused by WCT was obvious compared with JA (P<0.05). CONCLUSIONS: WCT
could improve analgesic effects in patients with NT-CS, which might be related to
increasing local blood perfusion of acupunct points.
PMID- 29340887
TI - Toward Evidence-Based Chinese Medicine: Status Quo, Opportunities and Challenges.
AB - How to test the treatments of Chinese medicine (CM) and make them more widely
accepted by practitioners of Western medicine and the international healthcare
community is a major concern for practitioners and researchers of CM. For
centuries, various approaches have been used to identify and measure the efficacy
and safety of CM. However, the high-quality evidence related to CM that produced
in China is still rare. Over the recent years, evidence-based medicine (EBM) has
been increasingly applied to CM, strengthening its theoretical basis. This paper
reviews the past and present state of CM, analyzes the status quo, challenges and
opportunities of basic research, clinical trials, systematic reviews, clinical
practice guidelines and clinical pathways and evidence-based education developed
or conducted in China, pointing out how EBM can help to make CM more widely used
and recognized worldwide.
PMID- 29340889
TI - Quantification of Myocardial Perfusion Defect Size in Rats: Comparison between
Quantitative Perfusion SPECT and Autoradiography.
AB - PURPOSE: Ultra-high resolution single-photon emission computed tomography (SPECT)
system, using multiple pinhole collimators, has been applied to the imaging of
small rodents. We aimed to compare the myocardial infarction (MI) area on
quantitative perfusion single-photon emission computed tomography (QPS; Cedars
Sinai Medical Center, USA) with that on high-resolution autoradiography in rat
model to determine the accuracy of perfusion defect measurement by QPS.
PROCEDURES: After thoracotomy, rats (n = 9) had their left coronary arteries
occluded and reperfused before injection with 185 MBq [99mTc]
methoxyisobutylisonitrile ([99mTc]MIBI) for SPECT and autoradiography. Healthy
rats (n = 28) were similarly scanned to create a normal database on which to base
QPS. The MI area on SPECT images was analysed automatically by QPS software. For
the autoradiography images, regions of interest for MI were set at 1 mm
intervals. RESULTS: In normal rats, [99mTc]MIBI accumulated throughout the left
ventricles, and a polar map of ventricular perfusion showed the lowest and
highest uptakes in the inferior (68 % +/- 4 %) and anterior (92 % +/- 5 %) walls,
respectively. In the rat MI model, the percentage of polar map with reduced
[99mTc]MIBI uptake correlated strongly with the percentage of left ventricle with
MI on autoradiography (r2 = 0.90). CONCLUSIONS: QPS can quantitatively evaluate
MI severity on myocardial perfusion images in rats, with comparable results to
autoradiography. This widely available software could promote the development of
new techniques for analysing cardiac images in small animals.
PMID- 29340891
TI - Mitomycin C 0.02 and 0.002% efficacy in preventing haze after photorefractive
keratectomy.
AB - PURPOSE: To compare MMC 0.002% efficacy in preventing haze after PRK in relation
to MMC 0.02%. PATIENTS AND METHODS: We conducted a prospective study with
patients with myopia or myopic astigmatism undergoing PRK in the same conditions.
After PRK, MMC was applied for 30 s in a concentration of 0.02% on the right eye
(group 1) and 0.002% on the left eye (group 2). Age, gender, spherical equivalent
and haze intensity (1, 3, 6 and 12 months postoperatively) were assessed. Haze
was quantified at biomicroscopy (0-4 +). P < 0.05 was considered statistical
significant. RESULTS: We evaluated 130 patients, 77 women and 53 men, with a mean
age of 30.2 +/- 9 years. The spherical equivalent was - 3.66 D in the group 1 and
- 3.77 D in the group 2. In the 1st month after PRK, incidence of haze was 13.9%
eyes in group 1 and 14.6% in group 2. In the 3rd month, incidence of haze was
50.0% eyes in group 1 and 48.5% in group 2 which presented with 3 +/4 + traces of
haze. In the 12th month, incidence of haze was 7.7% eyes in group 1 and 5.4% in
group 2. There was no correlation between haze and age (p = 0.279/0.333), gender
(p = 0.345/0.367) or spherical equivalent (p = 0.100/0.054) in groups 1 and 2,
respectively. There was no difference in haze between groups 1 and 2 (p = 0.56).
CONCLUSION: MMC 0.002% was effective in preventing haze after PRK. As MMC long
term safety has not been proved, we suggest its use in a lower concentration, in
order to prevent potential complications.
PMID- 29340890
TI - Association between average daily television viewing time and the incidence of
ovarian cancer: findings from the Japan Collaborative Cohort Study.
AB - PURPOSE: Seventy-five percent of epidemiological studies have reported that
sedentary behavior is associated with ovarian cancer incidence. Although Japan
has one of the most sedentary populations, with median sitting times of 7 h/day,
this association has not been investigated. This study aimed to elucidate the
association between average daily television (TV) viewing time, which is a major
sedentary behavior, and the incidence of ovarian cancer in a large-scale
nationwide cohort study in Japan. METHODS: A total of 34,758 female participants
aged 40-79 years without a history of cancer at baseline were included in the
study. The inverse probability weighted competing risk model was used to
calculate the hazard ratio (HR) and 95% confidence interval (CI) for the
incidence of ovarian cancer. RESULTS: During a median follow-up of 19.4 years, 59
participants developed ovarian cancer (ICD-10: C56), 2,706 participants developed
other types of cancer, and 4,318 participants died. Participants who watched TV
for >= 5 h/day were more likely to develop ovarian cancer than those who watched
TV for < 2 h/day (HR 2.15; 95% CI 1.54-2.99). CONCLUSION: Our findings suggest
that reducing the amount of time spent sedentarily may be beneficial for
preventing ovarian cancer.
PMID- 29340892
TI - A summer prematriculation program to help students succeed in medical school.
AB - Medical schools with a diverse student body face the challenge of ensuring that
all students succeed academically. Many medical schools have implemented
prematriculation programs to prepare students from diverse backgrounds; however,
evidence on their impact is largely lacking. In this study, we analyzed
participants' demographics as well as the impact of the prematriculation program
on Year 1 performance. Predictive validity of the program was assessed and
compared to other traditional predictors, including grade point average (GPA) and
Medical College Admission Test (MCAT) scores and subscores. Linear mixed effect
models determined the impact of the prematriculation program, and linear
regression analysis assessed the predictive value of the overall score in the
prematriculation program and other traditional predictors. Demographics of
students participating in the prematriculation program from 2013 to 2015 (n = 75)
revealed a significantly higher prevalence of academically disadvantaged students
including older students, students with lower GPA and MCAT scores and students of
racial and ethnic populations that are underrepresented in medicine, compared to
non-participants (n = 293). Participants performed significantly better in Year 1
courses that were covered in the prematriculation program compared to courses
that were not covered. The overall performance in the prematriculation program
correlated significantly with Year 1 performance and was found to be a strong
predictor for Year 1 performance. This study suggests that a prematriculation
program can help students to succeed in the first year of medical school. The
results have implications for medical schools seeking to implement or evaluate
the effectiveness of their prematriculation program.
PMID- 29340894
TI - Correction to: Burst Out of the Dead Land by the Help of Spirituality: A Case
Study of Living with Blindness and Cancer.
AB - In the original version of this article, there is a typo in the family name of
the author. The co-author family name should be Seyed Bagheri; instead, it has
been published as Seyed bagheri.
PMID- 29340893
TI - A Prospective Study of Humoral and Cellular Immune Responses to Hepatitis B
Vaccination in Habitual Marijuana Smokers.
AB - Exposure to Delta9-tetrahydrocannabinol (THC) in vitro and in animal models can
significantly impair the differentiation, activation and function of dendritic
cells, T cells and B cells. However, studies directly assessing the impact of
marijuana smoking on human immunity are lacking. A prospective study of immune
responses to a standard hepatitis B vaccination was therefore carried out in a
matched cohort of 9 marijuana smokers (MS) and 9 nonsmokers (NS). In addition to
their regular marijuana use, MS smoked four marijuana cigarettes in a monitored
setting on the day of each vaccination. Blood samples were collected over time to
assess the development of hepatitis B-specific immunity. The majority of subjects
from both the NS (8) and MS (6) groups developed positive hepatitis B surface
antibody titers (>10 IU/L) and of these 6 NS and 5 MS were classified as high
antibody (good) responders (>100 IU/L). The development of a good response
correlated with the presence of hepatitis B-specific T cell proliferation and
cytokine production, resulting in a clear distinction regarding the immune status
of good responders versus non-responders. However, even though there were
slighter more non-responders in the MS cohort, there were no significant
differences between MS and NS with respect to peripheral blood cell phenotypes or
vaccination-related changes in hepatitis B responses. While a larger cohort may
be required to rule out a small suppressive effect, our findings do not suggest
that habitual marijuana smoking exerts a major impact on the development of
systemic immunity to hepatitis B vaccination.
PMID- 29340895
TI - Confirming the Tripartite Structure of the Duke University Religion Index: A
Methodological Approach.
AB - The present study provided a methodological critique regarding psychometric
investigations of the Duke University Religion Index (DUREL) and its variants.
Nine hundred seventeen (630 females and 287 males) university students (M age =
19.24) completed the DUREL, the Personal Religious Inventory, and the Daily
Spiritual Experiences Scale online. Confirmatory factor analyses were performed
to assess a three-factor (organizational religious activity; non-organizational
religious activity; and intrinsic religiosity) and a unidimensional model of the
DUREL. Chi-square difference tests were performed, and Akaike information
criterion values and Bayesian information criterion values were compared between
the models, each of which supported the three-factor model for the DUREL over the
unidimensional model. Convergent validity for the three factors of the DUREL
emerged through Spearman's rho correlations with measures of personal prayer,
ritual religious attendance, religious integration, Closeness to the Divine. This
study concluded that the DUREL is a multidimensional measurement of religion for
use in English-speaking university students, and it provided a broad
methodological note regarding future investigations of measures of religion or
spirituality that possess an existing theoretical model.
PMID- 29340896
TI - Analysis of fecal microbiota in patients with functional constipation undergoing
treatment with synbiotics.
AB - This study was performed to identify changes to microbial composition after
treatment with synbiotics in patients with functional constipation and to define
the key microbiota in the pathogenesis of functional constipation. Fecal samples
from 53 patients diagnosed with chronic functional constipation according to the
Rome III criteria were analyzed using 16S rRNA sequencing. After treatment with
synbiotics for 1 month, fecal samples were collected from 36 patients; after a
total of 3 months, fecal samples were collected from 15 patients. The outcomes
were compared with the intestinal microbiota profiles of 53 healthy community
volunteers. The microbiota in the constipation group differed from that in the
treatment group and healthy group. After synbiotic treatment for 1 and 3 months,
the abundance of Escherichia/Shigella decreased, whereas that of Prevotella_9 and
Lactococcus increased. Comparison of the microbiota among the three groups showed
that Prevotella_9 was the characteristic bacteria that decreased in the
constipation group and increased in the treatment group. Synbiotic treatment can
improve the microbiota in patients with constipation. Identification of the key
bacterial genus is important to reveal the mechanism and provide a reliable
theoretical basis of synbiotic treatment. It will also promote relevant research
of microbiota treatment and individualized treatments.
PMID- 29340897
TI - Invasion and translocation of uropathogenic Escherichia coli isolated from
urosepsis and patients with community-acquired urinary tract infection.
AB - Uropathogenic Escherichia coli (UPEC) strains are found in high numbers in the
gut of patients with urinary tract infections (UTIs). We hypothesised that in
hospitalised patients, UPEC strains might translocate from the gut to the blood
stream and that this could be due to the presence of virulence genes (VGs) that
are not commonly found in UPEC strains that cause UTI only. To test this, E. coli
strains representing 75 dominant clonal groups of UPEC isolated from the blood of
hospitalised patients with UTI (urosepsis) (n = 22), hospital-acquired (HA) UTI
without blood infection (n = 24) and strains isolated from patients with
community-acquired (CA)-UTIs (n = 29) were tested for their adhesion to, invasion
and translocation through Caco-2 cells, in addition to the presence of 34 VGs
associated with UPEC. Although there were no differences in the rate and degree
of translocation among the groups, urosepsis and HA-UTI strains showed
significantly higher abilities to adhere (P = 0.0095 and P < 0.0001 respectively)
and invade Caco-2 cells than CA-UTI isolates (P = 0.0044, P = 0.0048
respectively). Urosepsis strains also carried significantly more VGs than strains
isolated from patients with only UTI and/or CA-UTI isolates. In contrast, the
antigen 43 allele RS218 was found more commonly among CA-UTI strains than in the
other two groups. These data indicate that UPEC strains, irrespective of their
source, are capable of translocating through gut epithelium. However, urosepsis
and HA-UTI strains have a much better ability to interact with gut epithelia and
have a greater virulence potential than CA-UPEC, which allows them to cause blood
infection.
PMID- 29340898
TI - Epidemiological aspects of healthcare-associated infections and microbial
genomics.
AB - Hospital-acquired infections (HAIs) are a cause of continuously increasing
morbidity and mortality. Most of these infections are caused by a limited set of
bacterial species, which share the capability to efficiently spread from patient
to patient and to easily acquire antibiotic resistance determinants. This renders
correct and rapid species identification and antibiotic susceptibility testing
(AST) important and underscores the relevance of bacterial epidemiological
typing. The latter is needed for the sensitive detection and exact tracing of
nosocomial spread of these potentially multidrug-resistant microorganisms (MDRO).
Many microbial typing technologies have been developed and put to some level of
executive practice, but it seems that the continued evolution in methodology has
currently reached an apex: there is likely to be scientific and practical
consensus on the ultimate typing potential of bacterial whole-genome sequencing
(WGS). The possibility to perform pan-genomic nucleotide-to-nucleotide
comparisons between strains belonging to a single species and to detect even
minute changes in nucleotide order will identify closely related organisms, while
upon accumulation of such mutations, independent descend can be assumed.
Calibration of difference levels [i.e. number of single nucleotide polymorphisms
(SNPs)] into categories of inter-strain relatedness needs to be performed in
order to generate robust, portable typing schemes. Here, we will briefly discuss
the state of affairs regarding bacterial epidemiology based upon WGS, its
relatedness with the nomenclature of former typing approaches and the continuing
need for a global typing language.
PMID- 29340899
TI - Assessing sensorimotor excitability after spinal cord injury: a reflex testing
method based on cycling with afferent stimulation.
AB - : Several studies have examined spinal reflex modulation during leg cycling in
healthy and spinal cord injury (SCI) subjects. However, the effect of cutaneous
plantar afferent input on spinal excitability during leg cycling after SCI has
not been characterised. The aim of the study was to test the feasibility of using
controlled leg cycling in combination with plantar cutaneous electrical
stimulation (ES) cycling to assess lower limb spinal sensorimotor excitability in
subjects with motor complete or incomplete SCI. Spinal sensorimotor excitability
was estimated by measuring cutaneomuscular-conditioned soleus H-reflex activity.
Reflex excitability was tested before and after a 10-min ES cycling session in 13
non-injured subjects, 6 subjects with motor incomplete SCI (iSCI) who had
moderately impaired gait function, 4 subjects with motor iSCI who had severely
impaired gait function, and 5 subjects with motor complete SCI (cSCI). No
modulation of soleus H-reflex with plantar cutaneous stimuli was observed after
either iSCI or cSCI when compared to non-injured subjects. However, after ES
cycling, reflex excitability significantly increased in subjects with iSCI and
moderately impaired gait function. ES cycling facilitated spinal sensorimotor
excitability only in subjects with motor iSCI with residual gait function.
Increased spinal excitability induced with a combination of exercise and afferent
stimulation could be adopted with diagnostic and prognostic purposes to reveal
the activity-based neurorehabilitation profile of individual subjects with motor
iSCI. TRIAL REGISTRATION: ISRCTN 26172500 ; retrospectively registered on 15 July
2016 Graphical abstract ?.
PMID- 29340900
TI - Xenin: the oldest after insulin?
AB - Xenin is a regulatory peptide first isolated from the human gastric mucosa. Using
an open-access protein database MEDLINE (33 million molecules; 11 billion amino
acid residues) and our original computer program, we conducted a search for the
xenin motifs in the primary structure of proteins across almost the entire
taxonomic range of evolution. Motifs with 40% homology to human xenin are already
present in prokaryotes. Homology reaches 84-96% in single-cell algae and plants,
becoming complete since bony fishes. We suppose that this regulatory peptide is
more ancient and significant than is usually thought.
PMID- 29340901
TI - Mental health-related quality of life and the timing of motherhood: a 16-year
longitudinal study of a national cohort of young Australian women.
AB - PURPOSE: We examine timing of motherhood in a longitudinal cohort of young
Australian women, and its relationship with mental health-related quality of life
(SF-36 MHI-5), and with sociodemographic, health behaviour and health-related
variables. METHODS: We analysed longitudinal self-report data from a nationally
representative cohort of 10,332 Australian women born 1973-1978, surveyed 6 times
between 1996 (aged 18-23) and 2012 (aged 34-39). RESULTS: Group-based trajectory
modelling identified four groups. Normative Mothers (46%, mean age at motherhood
30.5 years) made the transition to motherhood close to the Australian median age.
Early Mothers (25%, 25.2 years) and Very Early Mothers (7%, 20.0 years) made this
transition earlier; Not Mothers (22%) had not given birth. Generalised linear
mixed models showed that all groups improved mean MHI-5 scores over time.
Patterns of group differences were complex: Normative and Early Mothers scored
consistently highest; Very Early Mothers scored lowest at most surveys; Not
Mothers' scores increased relative to others over time. Most effects disappeared
after adjustment for confounders. Early and Very Early Mothers showed multiple
indicators of social disadvantage, while Not Mothers had very low rates of
marriage. CONCLUSIONS: Timing of motherhood is embedded in sociodemographic and
personal contexts. Women with socioeconomic advantages were characterised by
higher mental health-related quality of life and later transition to motherhood,
but adjustment for relative advantage attenuated differences in mental health
related quality of life. The overall findings suggest a pattern of positive
adaptation to circumstances, with mental health-related quality of life improving
through early adulthood regardless of timing of motherhood.
PMID- 29340902
TI - Validation Study of the Abbreviated Version of the Lubben Social Network Scale
Spanish Translation among Mexican and Mexican-American Older Adults.
AB - PURPOSE: To perform a face validity study of the Spanish version of the Lubben
Social Network Scale (LSNS-6) among Mexican and Mexican-American older adults.
DESIGN AND METHODS: A cross-national qualitative descriptive approach, based on
cognitive survey testing and cross-cultural equivalence analysis, was followed to
assess the face validity of the Spanish version of the LSNS-6. Data were
collected through 2 focus groups in Los Angeles (LA) and 4 in Mexico City (CDMX).
Focus groups followed a semi-structured guide. Eligibility criteria included
being 60 years and older, native Spanish speaking, and not suffering from
significant cognitive impairments. Four initial focus groups were targeted at
conducting a face validity assessment of the initial scale, which led to some
modifications. The two remaining focus groups reassessed the face validity of the
modified version of the Spanish LSNS-6. RESULTS: 56 older adults participated in
the focus groups yielding 152 pages of verbatim transcripts. Analysis of the
transcripts identified relevant themes affecting how Mexican and Mexican American
older adults understood the items from the LSNS-6 Spanish version, among them:
labelling of family members and friends, notions of neighborhood, identifying and
counting people, and understanding of "private matters". This led to propose a
modified Spanish version of the LSNS-6 following a name generating approach, as
well as some language and instruction modifications. The face validity of the
modified version suggested a better understanding. IMPLICATIONS: The study
proposes that the LSNS-6 Spanish version needs to be adapted for its use among
Mexican and Mexican American older adults, and we suggest a modified version.
This potentially implies that social isolation may be more accurately measured in
a vulnerable group of older adults. Further research is needed to ascertain the
construct validity and psychometric properties of the modified version.
PMID- 29340904
TI - Turkish Women's Knowledge, Attitudes, and Behaviors on Wet-Nursing, Milk Sharing
and Human Milk Banking.
AB - Purpose The aim of this study was to determine Turkish women's knowledge,
attitudes, and behaviors on wet-nursing, milk sharing, and human milk banking in
a primary care setting located in a semi-rural area. Description Donated human
milk is a feasible option for feeding infants and children. Currently, there is a
debate on the topic starts with the preparations to launch a human milk bank in a
large city in Turkey. Several previous papers reported women's opinions in large
hospital based studies. Little is known about women's views and practice on
donated human milk in the rural areas of Turkey. Assessment The study sample was
recruited among married women aged 15-49 years who had given birth within the
past 5 years and who were in a family health center for any reason in Honaz,
Denizli, Turkey. A total of 240 women were included in the study. The data were
collected by questionnaire created by the researchers and consisting of two
parts: sociodemographic characteristics, and women's knowledge, attitudes, and
behaviors on wet-nursing, milk sharing and human milk banking. Results Thirty
women (12.5%) had had a wet-nurse; 20 women (8.7%) wet-nursed babies before; and
17 (7.2%) of the women's children had a wet-nurse. If necessary, 80.9 and 78.3%
were willing to accept to do wet-nursing and milk sharing, respectively. 150
(62.5%) heard of human milk banks; 55 (22.9%) approved of the establishment of
milk banks. However, only 46 women (19.1%) were willing to donate to the bank.
Possibility of marriages between milk siblings (76.8%) was the main reason for
not considering the donation. Women's education was another factor affecting
their opinion on breast milk sharing and donation to human milk banks. Less
educated women were sympathetic to milk sharing (p = 0.02), however, more
educated mothers had a propensity to donate to milk banks (p = 0.02). Conclusion
Wet-nursing decreased over the years in Turkey, but still an ongoing small child
feeding method. Most of the women tend to become a wet nurse or do milk sharing
if it is needed, but they are hesitant to donate their milk to human milk banks,
mostly due to religious concerns.
PMID- 29340903
TI - Characterization of ent-kaurene synthase and kaurene oxidase involved in
gibberellin biosynthesis from Scoparia dulcis.
AB - Gibberellins (GAs) are ubiquitous diterpenoids in higher plants, whereas some
higher plants produce unique species-specific diterpenoids. In GA biosynthesis,
ent-kaurene synthase (KS) and ent-kaurene oxidase (KO) are key players which
catalyze early step(s) of the cyclization and oxidation reactions. We have
studied the functional characterization of gene products of a KS (SdKS) and two
KOs (SdKO1 and SdKO2) involved in GA biosynthesis in Scoparia dulcis. Using an in
vivo heterologous expression system of Escherichia coli, we found that SdKS
catalyzed a cyclization reaction from ent-CPP to ent-kaurene and that the SdKOs
oxidized ent-kaurene to ent-kaurenoic acid after modification of the N-terminal
region for adaptation to the E. coli expression system. The real-time PCR results
showed that the SdKS, SdKO1 and SdKO2 genes were mainly expressed in the root and
lateral root systems, which are elongating tissues. Based on these results, we
suggest that these three genes may be responsible for the metabolism of GAs in S.
dulcis.
PMID- 29340905
TI - Expression of VHL tumor suppressor mRNA and miR-92a in papillary thyroid
carcinoma and their correlation with clinical and pathological parameters.
AB - A growing body of evidence suggests a role of the von Hippel-Lindau (VHL) tumor
suppressor gene in the progression of papillary thyroid carcinoma (PTC). Our
previous study of VHL in PTCs showed that lower VHL expression was associated
with aggressive tumor features, but we found no evidence for VHL downregulation
through common genetic or epigenetic modifications. Several studies pointed to a
role of microRNA-92a (miR-92a) in the regulation of VHL expression in different
cancers. In the present study, we examined the expression levels of VHL mRNA and
miR-92a in 42 pairs of PTCs and matched non-tumor thyroid tissues by means of
quantitative RT-PCR. We explored the correlation between them and their
association with clinicopathological parameters. The results revealed that both
VHL and miR-92a were either up- or downregulated in PTCs compared to
corresponding non-tumor tissues. On univariate analysis, lower VHL levels were
significantly associated with extrathyroid spread (P = 0.022) and capsular
invasion (P = 0.032). Multivariate analysis confirmed the association of low VHL
with extrathyroid spread (OR 0.246, 95% CI 0.069-0.872, P = 0.038). Higher miR
92a among PTC tissues associated with the presence of nodal metastases
(univariate analysis: P = 0.012; multivariate: OR 4.703, 95% CI 1.109-19.938, P =
0.036). A negative correlation between VHL and miR-92a was observed in a subgroup
of PTCs having vascular invasion (P = 0.033, r = - 0.673). The data here reported
demonstrate that the expression of both VHL and miR-92a is deregulated in PTC
tissues and that in some PTCs they may have opposite roles. These roles, as well
as their diagnostic and/or prognostic utility, remain to be clarified.
PMID- 29340906
TI - An exploratory study on the intergenerational transmission of obesity and dieting
proneness.
AB - PURPOSE: There is a paucity of research exploring individuals' memories of
parental dieting behavior, engagement in "fat talk", or criticism of weight or
eating behavior in childhood. This exploratory study utilized a community sample
to further characterize the retrospective report of parenting dieting behavior.
METHODS: A total of 507 participants (78.1% females; 20.7% males; and 1.2%
transgender) were recruited to participate in an online, self-administered
survey. RESULTS: Forty percent (216) of participants reported maternal dieting in
their family of origin and 34% (182) reported maternal fat talk, 24% (120)
reported paternal dieting, and 11% recalled paternal 'fat talk' (58). Subgroup
analyses suggest that both male and female participants had greater odds of
remembering maternal rather than paternal weight or shape criticism and
encouragement to diet (OR = 58.1; and OR = 3.12; p < 0.0001 for male and female
participants, respectively). Retrospective report of indirect parental behaviors
(e.g. parental dieting) also appears to be associated with direct parental
behaviors (e.g. encouraging children to diet). Additionally, participants who
recalled maternal encouragement to diet reported a significantly higher adult BMI
(beta = 1.31, SE = 0.32, p < 0.0001). CONCLUSION: Results provide preliminary
evidence that a sizeable percentage of both adult male and female participants
recalled that their parents engaged in fat talk and dieting. In addition,
participants recalled parental criticism of their own weight or eating behaviors,
which was associated with recall of parental dieting and fat talk. LEVEL OF
EVIDENCE: Level V, Descriptive Study.
PMID- 29340907
TI - Harnessing a Different Dependency: How to Identify and Target Androgen Receptor
Positive Versus Quadruple-Negative Breast Cancer.
AB - The androgen receptor (AR) is a promising therapeutic target for a subset of
triple-negative breast cancers (TNBCs) in which AR is expressed. However, the
mechanistic action of AR and the degree to which primary and metastatic tumors
depend on AR, both before and after conventional treatment, remain to be defined.
We discuss preclinical and clinical data for AR+ TNBC, the difficulties in
monitoring AR protein levels, new methods for determining AR status, the
influence of AR on "stemness" in the context of TNBC, the role of combined
inhibition of sex steroid production and AR, and the role of AR in regulation of
the immune system. Although the exact role of AR in subsets of TNBC is still
being characterized, new therapies that target AR and the production of androgens
may provide additional options for patients with TNBC for whom chemotherapy is
currently the sole treatment option.
PMID- 29340908
TI - Fasting Blood Glucose Level in Locally Advanced Non-Small Cell Lung Cancer: a New
Prognostic Factor?
AB - Hyperglycemia may lead to proliferation, invasion, apoptosis inhibition,
migration, and eventually metastasis of cancer cells by several mechanisms. In
this study, the effect of hyperglycemia on overall survival (OS), disease-free
survival (DFS), and locoregional recurrence (LRR) was investigated in NSCLC. One
stage IIIA-IIIB NSCLC patient treated with chemoradiotherapy between 2010 and
2015 was enrolled. Fasting blood glucose (FBG) levels were recorded in pre
treatment, treatment, and post-treatment periods. Median age was 54 years (51
62). Fifty-two patients had squamous cell carcinoma (SCC); 19 had adenocarcinoma.
Median follow-up was 19 (11-30), median survival was 19 (13-24), and DFS was 9 (7
11) months. Diabetic patients had shorter survival than non-diabetics 12 (95%CI,
10-14) vs. 25 months (95%CI,18-32), p = 0.005. Number of patients with LRR was
also higher in diabetics compared to non-diabetics (8/12 vs. 11/37, p = 0.039).
OS was shorter in patients with hyperglycemic-FBG and diabetic-FBG levels in pre
treatment period (log-rank p = 0.03 and 0.023, respectively). Diabetic-FBG level
in pre-treatment period was found to be the only independent risk factor for
survival. In subgroup analysis, these differences were apparent in SCC (log-rank
p = 0.009 for hyperglicemic, log-rank p = 0.017 for diabetic-FBG). LRR was 68% in
patients with diabetic-FBG, 36.5% in patients with non-diabetic-FBG in post
treatment period (p = 0.015). Patients with LRR had significantly higher median
FBG value in post-treatment period compared to non-relapsing patients, 138 mg/dL
(119-228) and 111 mg/dL (99-164), respectively (p = 0.022). The patients with
hyperglycemic and diabetic-FBG levels in pre-treatment period had shorter
survival compared to normoglycemic ones. The patients with diabetic-FBG level in
post-treatment period had higher LRR, and relapsing patients had higher FBG
levels in post-treatment period.
PMID- 29340909
TI - Liposomal Amphotericin B as Monotherapy in Relapsed Coccidioidal Meningitis.
AB - Coccidioidal meningitis remains a difficult clinical problem, and despite life
long therapy with triazole antifungals, relapses of disease and medication
intolerance occur necessitating salvage treatment. We report two patients with
recurrent coccidioidal meningitis who improved following a 2-week course of
liposomal amphotericin B monotherapy and discuss potential advantages of this
treatment option.
PMID- 29340910
TI - Resistance Mechanism in a Terbinafine-Resistant Strain of Microsporum canis.
AB - To clarify the terbinafine (TRF) resistance mechanism in a TRF-resistant strain
of Microsporum canis, the expression of the pleiotropic drug resistance (PDR1),
multidrug resistance (MDR1), MDR2 and MDR4 genes were investigated by real-time
quantitative PCR (RT-qPCR) analysis, given the known interaction of the
corresponding proteins with antifungals and with the efflux blocker FK506. The
expression of the PDR1, MDR1, MDR2 and MDR4 genes was 2-4 times higher in the TRF
resistant strain grown in the presence of 0.14 ug/mL of TRF than in TRF
susceptible strains cultured in the absence of TRF. The TRF-resistant strain
exhibited MICs of > 32 ug/mL for TRF alone; this resistance was attenuated to an
MIC of 8 ug/mL in the presence of FK506, indicating that the TRF inhibitory
concentration index value was < 0.75. The additive effect of the efflux blocker
FK506 on TRF resistance was detected in the TRF-resistant strain. These results
indicated that the TRF resistance in this strain reflects overexpression of genes
encoding ABC transporter proteins.
PMID- 29340911
TI - Prevalence of Sexual Violence and its Association with Depression among Male and
Female Patients with Risky Drug Use in Urban Federally Qualified Health Centers.
AB - Sexual violence (SV) is common; however, the prevalence of SV and its long term
sequela vary geographically and among subpopulations within the USA. As such, the
aims of this study are the following: (1) to determine the prevalence of SV, (2)
to identify correlates of SV, and (3) to determine if SV is associated with
depression among male and female risky drug users in urban Federally Qualified
Health Centers (FQHCs) in Los Angeles. This study includes adult patients of five
urban FQHCs who self-reported risky drug use. We identified survivors of SV and
those experiencing depression through survey questions that queried, before or
after age 18, "Were you ever sexually assaulted, molested or raped?" and with the
RAND Mental Health Index (MHI-5). We utilized Pearson's chi-square tests to
assess predictors of SV and logistic regression to assess for an association
between SV and depression. Data collection took place from February 2011 to
November 2012. Of the 334 study patients, 49% of females and 25% of males
reported surviving SV. Exposure to SV, (both before 18 years of age and after 18
years of age) was the strongest predictor of depression among men and women in
this study (OR 4.7, p < 0.05). These data demonstrate that sexual violence is
prevalent in this urban FQHC population and is strongly associated with
depression. Providers should consider screening both men and women with risky
drug use for SV while health systems should continue to align mental health and
primary care services to appropriately care for these extremely vulnerable
patients. Trial Registration Clinical Trials. gov ID NCT01942876, Protocol ID
DESPR DA022445, http://www.clinicaltrials.gov.
PMID- 29340912
TI - Predictors of hypoglycemia in hospitalized patients with diabetes mellitus.
AB - Hypoglycemia is common among hospitalized patients with diabetes mellitus (DM),
and is associated with increased morbidity and mortality. Identify pre-admission
risk factors associated with in-hospital hypoglycemia. Historical prospectively
collected data of adult DM patients hospitalized to medical wards between 2011
and 2013. Hypoglycemia and serious hypoglycemia were defined as at least one
blood glucose measurement <= 70 and < 54 mg/dl, respectively, during
hospitalization. The primary outcome was in-hospital hypoglycemia. The cohort
included 5301 patients (mean age 73 +/- 13 years, 51% male), including 792
patients (15%) with hypoglycemia, among them 392 patients (7%) with serious
hypoglycemia. Patients with hypoglycemia or serious hypoglycemia during
hospitalization were older, compared to patients without hypoglycemia and more
likely to have chronic renal failure and cerebrovascular disease. Malignancy and
female gender were risk factors for hypoglycemia, but not for serious
hypoglycemia, while congestive heart failure was associated with increased risk
only for serious hypoglycemia. Diabetes mellitus' duration over 10 years was
associated with an almost threefold increased risk for hypoglycemia, compared to
DM duration less than a year. Insulin treatment and glycated hemoglobin > 9% were
also more common in patients with hypoglycemia. Insulin treatment was associated
with a fourfold increase in the risk for hypoglycemia among all glycated
hemoglobin categories. Our results identified several risk factors for in
hospital hypoglycemia in patients with DM. These findings may lead to appropriate
monitoring and early intervention to prevent hypoglycemia and to reduce morbidity
and mortality associated with in-hospital hypoglycemia.
PMID- 29340913
TI - A Randomized Pilot Trial of a Novel Behavioral Intervention for Chronic Pain
Tailored to Individuals with HIV.
AB - Chronic pain is an important and understudied comorbidity in people living with
HIV (PLWH). We conducted a pilot trial of Skills TO Manage Pain (STOMP), an
innovative social cognitive theory-based pain self-management intervention
tailored to PLWH, to assess feasibility, acceptability, and preliminary efficacy.
Eligibility criteria included being HIV+, >= moderate pain for >= 3 months and a
score of >= 4 on the three-item PEG pain severity and interference scale.
Participants were randomized in a 1:1 fashion to STOMP or a usual care
comparison. Among 22 participants randomized to STOMP, median session attendance
was 9/12 (75%). Of 19 STOMP participants surveyed, 13 reported being "much
better" overall since beginning treatment. Brief pain inventory-total scores
decreased by 2 points in the intervention group and 0.9 in the control group (p =
0.11). STOMP is feasible, acceptable, and shows preliminary evidence of efficacy
and promise for a full-scale trial.
PMID- 29340915
TI - Primed and unprimed rebounding illusory apparent motion.
AB - Although sequences of uncorrelated random dots can yield a wide range of
illusorily coherent motion percepts (including translation, rotation,
contraction, expansion, shear, and rebounding motion), past priming studies have
relied on two-alternative forced choice tasks that only measure unidirectional
(positive or negative) priming effects. In Experiment 1 we showed that when
participants are primed with unidirectional motion and given an additional option
to report bidirectional (rebounding) motion, they do so frequently, suggesting
that unidirectional motion can "default" to a rebounding percept. Furthermore,
rebounding percepts are more prevalent during trials with long frame durations,
suggesting a role for attention in forming and maintaining these illusory
percepts. In Experiment 2 we compared rebounding percepts that followed
unidirectional, drifting primes with rebounding percepts that followed
bidirectional, rebounding primes, and found that these two types of illusory
rebounding motion percepts differ systematically in their temporal structures. We
argue that rebounding percepts following drifting primes can be understood as a
breakdown of positive priming into an underlying oscillatory state, whereas
rebounding percepts following rebounding primes may be understood either as (1)
the initialization of the same oscillatory process, or (2) the entrainment of a
two-step motion pattern by a higher-order mechanism.
PMID- 29340914
TI - Structural Effects on HIV Risk Among Youth: A Multi-level Analysis.
AB - We proposed a multilevel model of structural influences on HIV-risky sexual
partnerships in a diverse sample of 1793 youth residing in 23 states and the
District of Columbia. We examined the influence of concentrated disadvantage, HIV
stigma, and sexual and gender minority stigma on engagement in HIV risky sexual
partnerships and whether youth's participation in opportunity structures,
anticipation of HIV stigma, and perceptions of their community as youth
supportive settings mediated structural effects. After controlling for age, HIV
status, and race, we found structural HIV stigma had deleterious indirect effects
on youth's participation in HIV-risky sexual partnerships. Concentrated
disadvantage and structural sexual and gender minority stigma had direct negative
effects on youth's perceptions of their communities as supportive and on their
participation in prosocial activity. Support perceptions had direct, protective
effects on avoidance of HIV-risky sexual partnerships. Structural stigma
undermines youth's belief that their communities invest in their safety and well
being.
PMID- 29340916
TI - Trapped in a tight spot: Scaling effects occur when, according to the action
specific account, they should not, and fail to occur when they should.
AB - The action-specific account of perception claims that what we see is perceptually
scaled according to our action capacity. However, it has been argued that this
account relies on an overly confirmatory research strategy-predicting the
presence of, and then finding, an effect (Firestone & Scholl, 2014). A
comprehensive approach should also test disconfirmatory predictions, in which no
effect is expected. In two experiments, we tested one such prediction based on
the action-specific account, namely that scaling effects should occur only when
participants intend to act (Witt, Proffitt, & Epstein, 2005). All participants
wore asymmetric gloves in which one glove was padded with extra material, so that
one hand was wider than the other. Participants visually estimated the width of
apertures. The action-specific account predicts that the apertures should be
estimated as being narrower for the wider hand, but only when participants intend
to act. We found this scaling effect when it should not have occurred (Exp. 1,
for participants who did not intend to act), as well as no effect when it should
have occurred (Exp. 2, for participants who intended to act but were given a
cover story for the visibility and position of their hands). Thus, the cover
story used in Experiment 2 eliminated the scaling effect found in Experiment 1.
We suggest that the scaling effect observed in Experiment 1 likely resulted from
demand characteristics associated with using a salient, unexplained manipulation
(e.g., telling people which hand to use to do the task). Our results suggest that
the action-specific account lacks predictive power.
PMID- 29340917
TI - Biliary Bypass with Laparoscopic Choledochoduodenostomy.
AB - Laparoscopic choledochoduodenostomy (LCDD) is employed to treat many benign
biliary diseases when endoscopic or percutaneous techniques are not feasible. We
describe our technique for LCDD, which utilizes common bile duct transection and
an end-to-side biliary-enteric anastomosis. This procedure includes the following
elements: isolation and transection of the common bile duct, mobilization of the
duodenum (Kocher maneuver), inspection of the common bile duct, and end-to-side
biliary-enteric anastomosis. Key details and pitfalls are discussed. Over a 5
year period, LCDD was performed on 18 patients. Indications included intractable
abdominal pain (10) and choledocholithiasis (8). The majority of patients, 83%,
tolerated the operation well with no complications. There was one postoperative
intra-abdominal abscess and two anastomotic strictures, one in the immediate
postoperative period and the other 9 months after the operation. The median
length of stay was 4 days (IQR 3.0-5.3), and there was minimal blood loss. Based
on our experience, LCDD with transection and end-to-side biliary-enteric
anastomosis is a safe and effective biliary bypass technique.
PMID- 29340919
TI - No-Touch Concept Is Invalid for Left-Dominant Perihilar Cholangiocarcinoma.
PMID- 29340918
TI - Validation of AAST EGS Grade for Acute Pancreatitis.
AB - BACKGROUND: The AAST recently developed an emergency general surgery (EGS)
disease grading system to measure anatomic severity. We aimed to validate this
grading system for acute pancreatitis and compare cross sectional imaging-based
AAST EGS grade and compare with several clinical prediction models. We
hypothesize that increased AAST EGS grade would be associated with important
physiological and clinical outcomes and is comparable to other severity grading
methods. METHODS: Single institution retrospective review of adult patients
admitted with acute pancreatitis during 10/2014-1/2016 was performed. Patients
without imaging were excluded. Imaging, operative, and pathological AAST grades
were assigned by two reviewers. Summary and univariate analyses were performed.
AUROC analysis was performed comparing AAST EGS grade with other severity scoring
systems. RESULTS: There were 297 patients with a mean (+/-SD) age of 55 +/- 17
years; 60% were male. Gallstone pancreatitis was the most common etiology (28%).
The overall complication, mortality, and ICU admission rates were 51, 1.3, and
25%, respectively. The AAST EGS imaging grade was comparable to other severity
scoring systems that required multifactorial data for readmission, mortality, and
length of stay. CONCLUSIONS: The AAST EGS grade for acute pancreatitis
demonstrates initial validity; patients with increasing AAST EGS grade
demonstrated longer hospital and ICU stays, and increased rates of readmission.
AAST EGS grades assigned using cross sectional imaging findings were comparable
to other severity scoring systems. Further studies should determine the
generalizability of the AAST system. LEVEL OF EVIDENCE: IV Study Type: Single
institutional retrospective review.
PMID- 29340920
TI - Pure Laparoscopic Transhepatic Enucleation of a Mucinous Cystic Neoplasm Abutting
the Major Hepatic Veins at the Hepatocaval Confluence (with Video).
AB - BACKGROUND: A mucinous cystic neoplasm (MCN) of the liver is a rare disease
entity, occurring predominantly in the left hemiliver as reported by Simo et al.1
Thomas et al.2 and Vogt et al.3 Surgical resection of tumors at the hepatocaval
confluence is a technically demanding procedure. Enucleation procedures have been
performed for the management of benign or premalignant lesions such as cystic
tumors as previously described by Thomas et al.2 and Vogt et al.3. We present a
patient who underwent pure laparoscopic transhepatic enucleation to treat a MCN
abutting the major hepatic veins at the hepatocaval confluence. METHODS: We
treated a 77-year-old man who presented with a 5-cm-sized cystic mass at the
hepatocaval confluence. Using the Pringle maneuver, we performed liver
parenchymal transection along the junction between the origin of the middle
hepatic vein (MHV) and the inferior vena cava (IVC) as reported by Kim4. The MHV
formed the left-sided boundary of the cystic mass. After dissection of the left
boundary of the cystic wall, the dorsal side of the cystic mass was carefully
dissected. Liver parenchymal transection was continued up to the right hepatic
vein (RHV). Laparoscopic enucleation was performed to expose the RHV and MHV, as
well as the IVC. RESULTS: The operation time was 270 min, the estimated blood
loss was 80 mL, and no transfusion was necessary in this patient. The final
histopathological diagnosis of the mass was MCN. Postoperatively, the patient
recovered uneventfully, and he was discharged on postoperative day 5.
CONCLUSIONS: Laparoscopic transhepatic enucleation for MCNs at the hepatocaval
confluence is technically feasible and offers the benefits of a parenchyma
sparing resection. However, this procedure requires a high level of technical
skills and shows a steep learning curve.
PMID- 29340921
TI - Hepatic Paragonimiasis Mimicking Hepatocellular Carcinoma.
AB - Paragonimiasis is a parasitic lung infection caused by lung flukes of the genus
Paragonimus. Ectopic infection may occur but rarely involves the liver. Here, we
report a case of hepatic paragonimiasis in a Chinese man who was initially
suspected to have hepatocellular carcinoma. He had been previously diagnosed with
chronic hepatitis B. No specific symptoms or abnormal blood test results were
observed, except for a significant rise in serum alfa-fetoprotein. Magnetic
resonance imaging revealed a 12-cm mass with inhomogeneous signal intensity at
the left lobe of the liver. Laparoscopic left hemihepatectomy was performed. He
was finally diagnosed as hepatic paragonimiasis upon pathological examination and
antibody serology. The postoperative course was uneventful. He received a
standard course of praziquantel and recovered well. Our case is unique in its
tumor-like characteristic and protrudes the difficulty of differential diagnosis
with both benignant and malignant hepatic diseases by imaging studies or non
specific symptoms. Hepatic paragonimiasis is unusual; however, it should be
considered in the differential diagnosis of liver malignancy by clinicians.
PMID- 29340922
TI - Prevention of Internal Hernia During Robotic Total Gastrectomy for Gastric
Cancer.
AB - BACKGROUND: Postoperative internal hernia (IH) is a potentially life-threatening
acute protrusion of viscus through an iatrogenic mesenteric defect. In our
retrospective study of 1943 consecutive gastric cancer (GC) patients who had
undergone surgery, the incidence of IH after laparoscopic total gastrectomy (LTG)
was 4.9%.1 This high incidence seems to be caused by decreased adhesion formation
after LTG. There is no consensus regarding orifice management during robotic
total gastrectomy (RTG). We therefore developed a new procedure for IH prevention
during RTG. METHODS: We performed RTG with antecolic Roux-en-Y reconstruction
using the da Vinci S system (Intuitive, Sunnyvale, CA). We chose an
intracorporeal side-to-side esophagojejunostomy (overlap method).2 First,
mesenteric defect of jejunojejunostomy was closed under direct vision following
retrieval of the stomach. Second, the esophagus hiatus and Petersen's defect were
closed under laparoscopic vision using robotic suture.3 Finally, the duodenal
stump and the Roux limb were fixed to prevent torsion of the Roux limb. RESULTS:
We performed this procedure on five patients between May and October 2017. The
median duration of surgery was 395 min (range, 319-442 min), median bleeding was
60 ml (range, 35-140 ml). There were no anastomosis-related complications higher
than Clavien-Dindo grade II in any patients.4 Although the follow-up period is
less than 1 year, no IH after RTG has been observed in any patients. CONCLUSION:
Regarding short-term surgical outcomes, this procedure is recommended for GC
patients who undergo RTG. However, more long-term follow-up for patients who have
undergone RTG with closure of all mesenteric defects is required.
PMID- 29340923
TI - CT Features of Calcifying Fibrous Tumor of the Stomach.
PMID- 29340924
TI - Impact of Preoperative Opioid Use After Emergency General Surgery.
AB - BACKGROUND: Preoperative exposure to narcotics has recently been associated with
poor outcomes after elective major surgery, but little is known as to how
preoperative opioid use impacts outcomes after common, emergency general surgical
procedures (EGS). METHODS: A high-volume, single-center analysis was performed on
patients who underwent EGS from 2012 to 2013. EGS was defined as the seven
emergent operations that account for 80% of the national burden. Preoperative
opioid use was defined as having an active opioid prescription within 7 days
prior to surgery. Chronic opioid use was defined as having an opioid prescription
concurrent with 90 days after discharge. RESULTS: A total of 377 patients
underwent EGS during the study period. Preoperative opioid use was present in 84
patients (22.3%). Preoperative opioid users had longer hospital LOS (10.5 vs 6
days), higher costs of care ($25,331 vs $11,454), and higher 30-day readmission
rates (22.6 vs 8.2%) compared with opioid-naive patients (p < 0.001 each). After
covariate adjustment, preoperative opioid use was predictive of LOS (RR 1.19
[1.01-1.41]) and 30-day hospital readmission (OR 2.69 [1.25-5.75]) (p < 0.05
each). Total direct cost was not different after modeling. Preoperative opioid
users required more narcotic refills compared with opioid-naive patients (5 vs 0
refills, p < 0.001). After discharge, 15.4% of opioid-naive patients met criteria
for chronic opioid use, vs 77.4% in preoperative opioid users (p < 0.001).
CONCLUSIONS: Preoperative opioid use is associated with greater resource
utilization after emergency general surgery, as well as vastly different
postoperative opioid prescription patterns. These findings may help to inform the
impact of preoperative opioid use on patient care, and its implications on
hospital and societal cost.
PMID- 29340925
TI - Response to Letter to the Editor on "Utility of Endoanal Ultrasonography in
Assessment of Primary and Recurrent Anal Fistulas and for Detection of Associated
Anal Sphincter Defects".
PMID- 29340926
TI - Gastrointestinal histoplasmosis ileal stricture successfully treated with through
the-scope balloon dilation in a patient with hyperimmunoglobulin M syndrome.
AB - Gastrointestinal histoplasmosis is common in patients with disseminated disease
affecting both immunocompetent and immunocompromised patients. However, it is
often unrecognized due to a lack of specific signs and symptoms. It has only
rarely been reported to cause small bowel obstruction, during which surgical
treatment was nearly always necessary. Little is known about the usefulness of
endoscopic therapy in gastrointestinal histoplasmosis associated strictures. We
report the case of a 32-year-old man with a history of hyperimmunoglobulin M
syndrome who presented with small bowel obstruction secondary to disseminated
gastrointestinal histoplasmosis. Treatment was successful with a through-the
scope balloon dilator in combination with medical therapy. This report adds to
the limited data available on the benefit of endoscopic therapy in infectious
strictures, particularly gastrointestinal histoplasmosis.
PMID- 29340927
TI - Achalasia Cardia in a Young Infant.
AB - Achalasia cardia is an esophageal motility disorder rarely reported in children
and more so in young infants. Common clinical presentations include vomiting,
dysphagia, regurgitation, recurrent pulmonary aspiration and failure to thrive.
Diagnosis is made by barium swallow study and esophageal manometry, which is the
gold standard test. Pharmocological management and endotherapy often fails and
results in recurrence of symptoms. Laparoscopic Hellers myotomy, with or without
anti-reflux procedure is the standard treatment of choice for children. Per-oral
endoscopic myotomy is utilized for treatment of achalasia in adults, but its
safety, efficacy, and feasibility is not studied in children.
PMID- 29340930
TI - The Microbiome and Neurologic Disease: Past and Future of a 2-Way Interaction.
PMID- 29340928
TI - Microbiota Signaling Pathways that Influence Neurologic Disease.
AB - Though seemingly distinct and autonomous, emerging evidence suggests there is a
bidirectional interaction between the intestinal microbiota and the brain. This
crosstalk may play a substantial role in neurologic diseases, including anxiety,
depression, autism, multiple sclerosis, Parkinson's disease, and, potentially,
Alzheimer's disease. Long hypothesized by Metchnikoff and others well over 100
years ago, investigations into the mind-microbe axis is now seeing a rapid
resurgence of research. If specific pathways and mechanisms of interaction are
understood, it could have broad therapeutic potential, as the microbiome is
environmentally acquired and can be modified to promote health. This review will
discuss immune, endocrine, and neural system pathways that interconnect the gut
microbiota to central nervous system and discuss how these findings might be
applied to neurologic disease.
PMID- 29340931
TI - VascuTrainer: A Mobile and Disposable Bioreactor System for the Conditioning of
Tissue-Engineered Vascular Grafts.
AB - In vitro tissue engineering of vascular grafts requires dynamic conditioning in a
bioreactor system for in vitro tissue maturation and remodeling to receive a
mechanically adequate and hemocompatible implant. The goal of the current work
was to develop a bioreactor system for the conditioning of vascular grafts which
is (i) able to create a wide range of flow, pressure and frequency conditions,
including physiological ones; (ii) compact and easy to assemble; (iii)
transportable; (iv) disposable. The system is driven by a small centrifugal pump
controlled via a custom-made control unit, which can also be operated on
batteries to allow for autonomous transportation. To show the potential of the
newly developed bioreactor system small-caliber vascular composite grafts (n = 5,
internal diameter = 3 mm, length = 12.5 cm) were fabricated using a fibrin
scaffold embedding human umbilical artery smooth muscle cells and a
polyvinylidene fluoride warp-knitted macroporous mesh. Subsequently, the vascular
grafts were endothelialized and mounted in the bioreactor system for
conditioning. The conditioning parameters remained within the predefined range
over the complete conditioning period and during operation on batteries as tested
for up to 25 h. Fabrication and pre-conditioning under arterial pressure and
shear stress conditions resulted in robust and hemocompatible tissue-engineered
vascular grafts. Analysis of immunohistochemical stainings against extracellular
matrix and cell-specific proteins revealed collagen I and collagen III
deposition. The luminal surface was confluently covered with endothelial cells.
The developed bioreactor system showed cytocompatibility and pH, pO2, pCO2,
glucose and lactate stayed constant. Sterility was maintained during the complete
fabrication process of the vascular grafts. The potential of a versatile and
mobile system and its functionality by conditioning tissue-engineered vascular
grafts under physiological pressure and flow conditions could be demonstrated.
PMID- 29340932
TI - Robotic Scanning Device for Intraoperative Thyroid Gland Endomicroscopy.
AB - Probe-based confocal laser endomicroscopy has a high potential to be a promising
tool that can provide intraoperative high-resolution in vivo morphological
imaging at cellular and subcellular levels for thyroidectomy, and allow real-time
assessment of tumor margins. However, the typical images acquired with this
technique cover a very small area limited by the field of view of the probe,
accompanied by tissue deformation and inconsistent probe-tissue contact when
operated manually. In this paper, a novel compact robotic device for large area
scanning has been developed. The device can scan a large surface in a spiral
trajectory by rotating the tip frame along the spiral groove of the base frame.
The fiber Bragg grating sensor with a passive linear structure is used to detect
and maintain a stable probe-tissue contact force during scanning. An active
linear actuation is also integrated for adjusting the probe-tissue contact level
prior to each scan. Results demonstrate that the scanning device ensures a
suitable probe-tissue contact force and compensates for simulated hand tremor.
Mosaicing results of lens tissue paper and porcine belly tissue with both bench
and hand-held experiments show the effectiveness and usability of the device,
demonstrating the potential clinical value of the system.
PMID- 29340933
TI - Forces Generated by Vastus Lateralis and Vastus Medialis Decrease with Increasing
Stair Descent Speed.
AB - Stair descent (SD) is a common, difficult task for populations who are elderly or
have orthopaedic pathologies. Joint torques of young, healthy populations during
SD increase at the hip and ankle with increasing speed but not at the knee,
contrasting torque patterns during gait. To better understand the sources of the
knee torque pattern, we used dynamic simulations to estimate knee muscle forces
and how they modulate center of mass (COM) acceleration across SD speeds (slow,
self-selected, and fast) in young, healthy adults. The vastus lateralis and
vastus medialis forces decreased from slow to self-selected speeds as the
individual lowered to the next step. Since the vasti are primary contributors to
vertical support during SD, they produced lower forces at faster speeds due to
the lower need for vertical COM support observed at faster speeds. In contrast,
the semimembranosus and rectus femoris forces increased across successive speeds,
allowing the semimembranosus to increase acceleration downward and forward and
the rectus femoris to provide more vertical support and resistance to forward
progression as SD speed increased. These results demonstrate the utility of
dynamic simulations to extend beyond traditional inverse dynamics analyses to
gain further insight into muscle mechanisms during tasks like SD.
PMID- 29340929
TI - S-Adenosyl Methionine and Transmethylation Pathways in Neuropsychiatric Diseases
Throughout Life.
AB - S-Adenosyl methionine (SAMe), as a major methyl donor, exerts its influence on
central nervous system function through cellular transmethylation pathways,
including the methylation of DNA, histones, protein phosphatase 2A, and several
catecholamine moieties. Based on available evidence, this review focuses on the
lifelong range of severe neuropsychiatric and neurodegenerative diseases and
their associated neuropathologies, which have been linked to the deficiency/load
of SAMe production or/and the disturbance in transmethylation pathways. Also
included in this review are the present-day applications of SAMe in the treatment
in these diseases in each age group.
PMID- 29340934
TI - Impact Force, Polar Gap and Modal Parameters Predict Acetabular Cup Fixation: A
Study on a Composite Bone.
AB - The balanced initial fixation of an implant makes up a crucial condition for its
long-term survival. However, the quantification of initial fixation is no easy
task and, to date, only qualitative assessments can be made. Although the concept
of measuring fixation by means of vibration analysis is already widely used in
dental implantology, the rigorous application of this method for the assessment
of the fixation of femoral and acetabular components remains a challenge.
Moreover, most studies on this subject have tended to focus solely on the femoral
stem even though acetabular cup fixation is also important and even more
difficult with respect to qualitative measurement. This study describes a
comprehensive experiment aimed at assessing acetabular cup fixation. Fixation is
expressed in terms of the impact force and polar gap variables, which are
correlated with the modal properties of the acetabular implant during the various
insertion stages. The predictive capabilities of modal frequencies and frequency
functions were investigated by means of surrogate models based on the Gaussian
process and functional principal component analysis. The prediction accuracy of
the proposed models was in the range 82-94%. The results indicate that natural
frequencies, reduced frequency, impact force and polar gap features provide great
potential in terms of the prediction of implant fixation.
PMID- 29340935
TI - Endoscopic Treatments of GERD.
AB - OPINION STATEMENT: PURPOSE OF REVIEW: Endoscopic therapies for gastroesophageal
reflux disease (GERD) are minimally invasive techniques which fill the gap
between the medical therapy with proton pump inhibitors (PPIs) and surgical
fundoplication. The main endoscopic therapies currently available in the USA are
transoral incisionless fundoplication (TIF) using EsophyX device or less
commonly, Medigus Ultrasonic Surgical Endostapler, and radiofrequency energy
delivery to lower esophageal sphincter using Stretta device. Our aim was to
examine the available evidence for these therapies. RECENT FINDINGS: Consistent
evidence for subjective improvement is available for fundoplication using EsophyX
and Stretta, but improvement in objective parameters for GERD is not seen or
evaluated in all the studies. There is a reduction in long-term efficacy seen
with TIF and also to a lesser extent with Stretta. Endoscopic therapies do not
replace surgical fundoplication and therefore are useful in patients with
breakthrough symptoms on PPI such as regurgitation or those reluctant to take
long-term PPI. An ideal patient is one who has symptoms and objective evidence of
GERD such as abnormal pH study or erosive esophagitis without any significant
anatomic distortion such as a hiatal hernia. Since these are endoluminal
procedures, they do not address the hiatal hernia reduction or repair of crural
defect. Adequate training in the technique and careful patient selection are
essential prior to embarking on these procedures.
PMID- 29340936
TI - Application of Color Transformation Techniques in Pediatric Spinal Cord MR
Images: Typically Developing and Spinal Cord Injury Population.
AB - The purpose of this study was to evaluate an improved and reliable visualization
method for pediatric spinal cord MR images in healthy subjects and patients with
spinal cord injury (SCI). A total of 15 pediatric volunteers (10 healthy subjects
and 5 subjects with cervical SCI) with a mean age of 11.41 years (range 8-16
years) were recruited and scanned using a 3.0T Siemens Verio MR scanner. T2
weighted axial images were acquired covering entire cervical spinal cord level C1
to C7. These gray-scale images were then converted to color images by using five
different techniques including hue-saturation-value (HSV), rainbow, red-green
blue (RGB), and two enhanced RGB techniques using automated contrast stretching
and intensity inhomogeneity correction. Performance of these techniques was
scored visually by two neuroradiologists within three selected cervical spinal
cord intervertebral disk levels (C2-C3, C4-C5, and C6-C7) and quantified using
signal to noise ratio (SNR) and contrast to noise ratio (CNR). Qualitative and
quantitative evaluation of the color images shows consistent improvement across
all the healthy and SCI subjects over conventional gray-scale T2-weighted
gradient echo (GRE) images. Inter-observer reliability test showed moderate to
strong intra-class correlation (ICC) coefficients in the proposed techniques (ICC
> 0.73). The results suggest that the color images could be used for
quantification and enhanced visualization of the spinal cord structures in
addition to the conventional gray-scale images. This would immensely help towards
improved delineation of the gray/white and CSF structures and further aid towards
accurate manual or automatic drawings of region of interests (ROIs).
PMID- 29340937
TI - Association between Electronic Medical Record Implementation of Default Opioid
Prescription Quantities and Prescribing Behavior in Two Emergency Departments.
PMID- 29340939
TI - The Influence of Financial Strain on Health Decision-Making.
PMID- 29340938
TI - Pharmacologic Treatment of Hypertensive Urgency in the Outpatient Setting: A
Systematic Review.
AB - BACKGROUND: Hypertensive urgency (HU), defined as acute severe uncontrolled
hypertension without end-organ damage, is a common condition. Despite its
association with long-term morbidity and mortality, guidance regarding immediate
management is sparse. Our objective was to summarize the evidence examining the
effects of antihypertensive medications to treat. METHODS: We searched the
PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Database of
Abstracts of Reviews of Effects (DARE), Cochrane Database of Systematic Reviews,
Web of Science, Google Scholar, and Embase through May 2016. STUDY SELECTION: We
evaluated prospective controlled clinical trials, case-control studies, and
cohort studies of HU in emergency room (ER) or clinic settings. We initially
identified 11,223 published articles. We reviewed 10,748 titles and abstracts and
identified 538 eligible articles. We assessed the full text for eligibility and
included 31 articles written in English that were clinical trials or cohort
studies and provided blood pressure data within 48 h of treatment. Studies were
appraised for risk of bias using components recommended by the Cochrane
Collaboration. The main outcome measured was blood pressure change with
antihypertensive medications. Since studies were too diverse both clinically and
methodologically to combine in a meta-analysis, tabular data and a narrative
synthesis of studies are presented. RESULTS: We identified only 20 double-blind
randomized controlled trials and 12 cohort studies, with 262 participants in
prospective controlled trials. However, we could not pool the results of studies.
In addition, comorbidities and their potential contribution to long-term
treatment of these subjects were not adequately addressed in any of the reviewed
studies. CONCLUSIONS: Longitudinal studies are still needed to determine how best
to lower blood pressure in patients with HU. Longer-term management of
individuals who have experienced HU continues to be an area requiring further
study, especially as applicable to care from the generalist.
PMID- 29340940
TI - Characterizing Potentially Preventable Admissions: A Mixed Methods Study of
Rates, Associated Factors, Outcomes, and Physician Decision-Making.
AB - BACKGROUND: Potentially preventable admissions are a target for healthcare cost
containment. OBJECTIVE: To identify rates of, characterize associations with, and
explore physician decision-making around potentially preventable admissions.
DESIGN: A comparative cohort study was used to determine rates of potentially
preventable admissions and to identify associated factors and patient outcomes. A
qualitative case study was used to explore physicians' clinical decision-making.
PARTICIPANTS: Patients admitted from the emergency department (ED) to the general
medicine (GM) service over a total of 4 weeks were included as cases (N = 401).
Physicians from both emergency medicine (EM) and GM that were involved in the
cases were included (N = 82). APPROACH: Physicians categorized admissions as
potentially preventable. We examined differences in patient characteristics,
admission characteristics, and patient outcomes between potentially preventable
and control admissions. Interviews with participating physicians were conducted
and transcribed. Transcriptions were systematically analyzed for key concepts
regarding potentially preventable admissions. KEY RESULTS: EM and GM physicians
categorized 22.2% (90/401) of admissions as potentially preventable. There were
no significant differences between potentially preventable and control admissions
in patient or admission characteristics. Potentially preventable admissions had
shorter length of stay (2.1 vs. 3.6 days, p < 0.001). There was no difference in
other patient outcomes. Physicians discussed several provider, system, and
patient factors that affected clinical decision-making around potentially
preventable admissions, particularly in the "gray zone," including risk of
deterioration at home, the risk of hospitalization, the cost to the patient, and
the presence of outpatient resources. Differences in provider training, risk
assessment, and provider understanding of outpatient access accounted for
differences in decisions between EM and GM physicians. CONCLUSIONS: Collaboration
between EM and GM physicians around patients in the gray zone, focusing on
patient risk, cost, and outpatient resources, may provide an avenues for reducing
potentially preventable admissions and lowering healthcare spending.
PMID- 29340941
TI - Internal Medicine Residents' Attitudes Toward Simulated Depressed Cardiac
Patients During an Objective Structured Clinical Examination: A Randomized Study.
AB - BACKGROUND: Physician biases toward mental conditions such as depression have
been shown to adversely affect medical outcomes. OBJECTIVE: To explore the
relationship between residents' explicit bias toward depressed patients and their
clinical skills on a cardiac case during an objective structured clinical exam
(OSCE). DESIGN: Prospective parallel randomized controlled study. PARTICIPANTS:
One hundred eighty-five internal medicine residents from three residency programs
in two states. INTERVENTION: During October-November 2015, residents were
randomized to either a depressed or non-depressed standardized patient (SP)
presenting with acute chest pain. MAIN MEASURES: The Medical Condition Regard
Scale (MCRS) assessed residents' explicit bias toward patients with depression.
Their clinical skills (history-taking, physical examination, patient counseling,
patient-physician interaction (PPI), differential diagnosis, and workup plan) and
facial expressions were rated during an OSCE. KEY RESULTS: No significant
relationships were found between resident explicit bias and clinical skill
measurements. Residents who examined the depressed SP scored lower, on average,
on history-taking (t [183] = -2.77, p < 0.01, Cohen's d = 0.41) and higher on PPI
(t [183] = 2.24, p < 0.05, Cohen's d = 0.33) than residents examining the non
depressed SP. There were no differences, on average, between stations on physical
examination, counseling, correct diagnosis, workup plan, or overall SP
satisfaction. Facial recognition software demonstrated that residents with a non
depressed SP had more neutral expressions than depressed-SP residents (t [133] =
2.46, p < 0.05, Cohen's d = 0.46), and residents with a depressed SP had more
disgusted expressions than non-depressed-SP residents (t [83.52] = 2.10, p <
0.05, Cohen's d = 0.28). CONCLUSIONS: Extrinsic bias did not predict OSCE
performance in this study. Some differences were noted in the OSCE performance
between the two stations. Further study is needed to examine the effects of
patient mental health conditions on physician examination procedures, diagnostic
behaviors, and patient outcomes.
PMID- 29340942
TI - Gluteal Augmentation-Associated Mycobacterial Infection.
PMID- 29340943
TI - A prospective investigation of rumination and executive control in predicting
overgeneral autobiographical memory in adolescence.
AB - The CaR-FA-X model (Williams et al., 2007), or capture and rumination (CaR),
functional avoidance (FA), and impaired executive control (X), is a model of
overgeneral autobiographical memory (OGM). Two mechanisms of the model,
rumination and executive control, were examined in isolation and in interaction
in order to investigate OGM over time. Across two time points, six months apart,
a total of 149 adolescents (13-16 years) completed the minimal-instruction
autobiographical memory test, a measure of executive control with both emotional
and nonemotional stimuli, and measures of brooding rumination and reflective
pondering. The results showed that executive control for emotional information
was negatively associated with OGM, but only when reflective pondering levels
were high. Therefore, in the context of higher levels of reflective pondering,
greater switch costs (i.e., lower executive control) when processing emotional
information predicted a decrease in OGM over time.
PMID- 29340944
TI - Persons with disability, social deprivation and an emergency medical admission.
AB - BACKGROUND: The community level of disability and social deprivation may result
in an emergency hospitalisation; we have examined the annual admission incidence
rate for emergency medical conditions in relation to the community prevalence of
such factors. METHODS: All emergency medical admissions (96,305 episodes in
50,612 patients) within the institution's catchment area were examined between
2002 and 2016. The frequency of disability, level of full-time carers and
unemployment for the 74 electoral divisions of the catchment area was regressed
against admission rates; incidence rate ratios (IRR) were calculated using
truncated Poisson regression. RESULTS: Disability was present in 12.1% of the
catchment area population (95% CI = 9.7-15.0). The annual admission incidence
rates/1000 population across disability quintiles for the more affluent areas
increased from Q1 7.6 (95% CI = 7.4-7.8) to Q5 27.3 (95% CI = 27.0-27.5) and for
the more deprived area from Q1 16.6 (95% CI = 16.4, 16.8) to and Q5 40.4 (95% CI
= 40.1-40.7). Disability status influenced the overall admission IRR (compared
with Q1/Q3) for Q4/Q5 1.11 (95% CI = 1.09-1.13) showing an increased rate of
hospitalisation for the more deprived areas. Community disability levels
interacted with local area unemployment and frequency of full-time carers; as
they increased, a linear relationship between disability and the admission rate
incidence was demonstrated. CONCLUSION: Local catchment area disability
prevalence rates in addition to social deprivation factors are an important
determinant of the annual incidence rate of emergency medical admissions.
PMID- 29340945
TI - Electromagnetic induction sensor for dynamic testing of coagulation process.
AB - With the increasing demand for coagulation POCT for patients in the surgery
department or the ICU, rapid coagulation testing techniques and methods have
drawn widespread attention from scholars and businessmen. This paper proposes the
use of electromagnetic induction sensor probe for detection of dynamic process
causing changes in the blood viscosity and density before and after coagulation
based on the damped vibration principle, in order to evaluate the coagulation
status. Utilizing the dynamic principle, the differential equation of vibration
system comprising elastic support and electromagnetic induction device is
established through sensor dynamic modeling. The structural parameters of elastic
support are optimized, and the circular sheet spring is designed. Furthermore,
harmonic response analysis and vibration fatigue coupling analysis are performed
on the elastic support of the sensor by considering the natural frequency of the
system, and the electromagnetic induction sensor testing device is set up. Using
the device and coagulation reagent, the standard curve for coagulation POCT is
plotted, and the blood sample application in clinical patients is established,
which are methodologically compared with the imported POCT coagulation analyzer.
The results show that the sensor designed in this paper has a first-order natural
frequency of 11.368 Hz, which can withstand 5.295 * 102 million times of
compressions and rebounds. Its correlation with the results of SONOCLOT analyzer
reaches 0.996, and the reproducibility 0.002. The electromagnetic induction
coagulation testing sensor designed has good elasticity and anti-fatigue, which
can meet the accuracy requirement of clinical detection. This study provides the
core technology for developing the electromagnetic induction POCT instrument for
dynamic testing of coagulation process.
PMID- 29340946
TI - Standardisation of shielding of medical X-ray installations.
PMID- 29340947
TI - The impact of depuration on mussel hepatopancreas bacteriome composition and
predicted metagenome.
AB - Due to the rapid elimination of bacteria through normal behaviour of filter
feeding and excretion, the decontamination of hazardous contaminating bacteria
from shellfish is performed by depuration. This process, under conditions that
maximize shellfish filtering activity, is a useful method to eliminate
microorganisms from bivalves. The microbiota composition in bivalves reflects
that of the environment of harvesting waters, so quite different bacteriomes
would be expected in shellfish collected in different locations. Bacterial
accumulation within molluscan shellfish occurs primarily in the hepatopancreas.
In order to assess the effect of the depuration process on these different
bacteriomes, in this work we used 16S RNA pyrosequencing and metagenome
prediction to assess the impact of 15 h of depuration on the whole hepatopancreas
bacteriome of mussels collected in three different locations.
PMID- 29340948
TI - A Case of Concomitant Pemphigus Foliaceus and Oral Pemphigus Vulgaris.
AB - Pemphigus is a chronic autoimmune condition that can affect multiple areas of the
body. The two main subtypes of pemphigus are pemphigus vulgaris (PV) and
pemphigus foliaceus (PF) which can rarely occur concurrently or even transition
from one to the other. The process of transition may be explained by qualitative
changes in desmoglein autoantibody profile. We present a rare case of concomitant
PF and oral PV and explore the literature on transitions between pemphigus
subtypes and whether this case could represent a transition from PF to PV.
Furthermore, the realities of multidisciplinary patient management are discussed.
PMID- 29340949
TI - Hybrid Central Odontogenic Fibroma/Central Giant Cell Lesion: A Missing Report.
PMID- 29340950
TI - Dermatologic Lesions Submitted to an Oral and Maxillofacial Pathology Biopsy
Service: An Analysis of 2487 Cases.
AB - Skin lesions are often submitted to oral and maxillofacial pathology practices.
The purpose of this study is to evaluate the frequency, distribution,
variability, and composition of dermatologic lesions within a large oral and
maxillofacial pathology biopsy service. An IRB-approved retrospective search of
skin lesions diagnosed at University of Florida oral and maxillofacial pathology
biopsy service between 1994 and 2015 was performed. 2487 cases were included in
the study. Gender was reported in 2466 cases, of which 59% were male and 41%
female. Age was provided in 2367 cases and ranged from 2 weeks to 96 years with
an average of 55 years. Location was indicated in 2473 cases. Lips were the most
common (41.7%), followed by face (25.3%), neck (7.4%), nose (6.5%), periorbital
(5.3%), ear (4.1%), and scalp (3.8%). Of the 2487 cases, five diagnoses (actinic
keratosis/cheilitis, intradermal nevus, epidermal inclusion cyst, seborrheic
keratosis, and basal cell carcinoma) constituted 84.4% of the cases. 69 of 2487
cases (2.8%) resulted in dermatopathologic consultation prior to final reporting.
Skin lesions accounted for ~ 1.0% of all lesions submitted to an oral and
maxillofacial pathology biopsy service. This study found a large variation in the
dermatologic lesions submitted to an oral pathology biopsy service. Although most
were routine in complexity, dermatopathology consultation was an important tool
in the diagnosis of the more challenging cases. This study may help pathologists
gain a better understanding of the frequency and variability of dermatologic
lesions submitted to an oral and maxillofacial pathology biopsy service and
promote more interdisciplinary consultation within the field. This study
evaluated the incidence and scope of dermatologic lesions submitted to a large
oral and maxillofacial pathology biopsy service over a long time period. A wide
scope of lesions was found, and dermatopathology consultation was important to
quality assurance.
PMID- 29340952
TI - RFAthM6A: a new tool for predicting m6A sites in Arabidopsis thaliana.
AB - KEY MESSAGE: We curated a reliable dataset of m6A sites in Arabidopsis thaliana,
built competitive models for predicting m6A sites, extracted predominant rules
from the prediction models and analyzed the most important features. In
biological RNA, approximately 150 chemical modifications have been discovered, of
which N6-methyladenine (m6A) is the most prevalent and abundant. This
modification plays an essential role in a myriad of biological mechanisms and
regulates RNA localization, nuclear export, translation, stability, alternative
splicing, and other processes. However, m6A-seq and other wet-lab techniques do
not easily facilitate accurate and complete determination of m6A sites across the
transcriptome. Therefore, the use of computational methods to establish accurate
models for predicting m6A sites is essential. In this work, we manually curated a
reliable dataset of m6A sites and non-m6A sites and developed a new tool called
RFAthM6A for predicting m6A sites in Arabidopsis thaliana. Briefly, RFAthM6A
consists of four independent models named RFPSNSP, RFPSDSP, RFKSNPF and RFKNF and
strict benchmarks show that the AUC values of the four models reached 0.894,
0.914, 0.920 and 0.926, respectively in a fivefold cross validation and the
prediction performance of RFPSDSP, RFKSNPF and RFKNF exceeded that of three
previously reported models (AthMethPre, M6ATH and RAM-NPPS). Linear combination
of the prediction scores of RFPSDSP, RFKSNPF and RFKNF improved the prediction
performance. We also extracted several predominant rules that underlie the m6A
site identification from the trained models. Furthermore, the most important
features of the predictors for the m6A site identification were also analyzed in
depth. To facilitate use of our proposed models by interested researchers, all
the source codes and datasets are publicly deposited at
https://github.com/nongdaxiaofeng/RFAthM6A .
PMID- 29340951
TI - A perspective on multi-target drug discovery and design for complex diseases.
AB - Diseases of infection, of neurodegeneration (such as Alzheimer's and Parkinson's
diseases), and of malignancy (cancers) have complex and varied causative factors.
Modern drug discovery has the power to identify potential modulators for multiple
targets from millions of compounds. Computational approaches allow the
determination of the association of each compound with its target before chemical
synthesis and biological testing is done. These approaches depend on the prior
identification of clinically and biologically validated targets. This Perspective
will focus on the molecular and computational approaches that underpin drug
design by medicinal chemists to promote understanding and collaboration with
clinical scientists.
PMID- 29340953
TI - MdPIN1b encodes a putative auxin efflux carrier and has different expression
patterns in BC and M9 apple rootstocks.
AB - KEY MESSAGE: Lower promoter activity is closely associated with lower MdPIN1b
expression in the M9 interstem, which might contribute to the dwarfing effect in
apple trees. Apple trees grafted onto dwarfing rootstock Malling 9 (M9) produce
dwarfing tree architecture with high yield and widely applying in production.
Previously, we have reported that in Malus 'Red Fuji' (RF) trees growing on M9
interstem and Baleng Crab (BC) rootstock, IAA content was relatively higher in
bark tissue of M9 interstem than that in scion or rootstock. As IAA polar
transportation largely depends on the PIN-FORMED (PIN) auxin efflux carrier.
Herein, we identify two putative auxin efflux carrier genes in Malus genus,
MdPIN1a and MdPIN1b, which were closely related to the AtPIN1. We found that
MdPIN1b was expressed preferentially in BC and M9, and the expression of MdPIN1b
was significantly lower in the phloem of M9 interstem than that in the scion and
rootstock. The distinct expression of MdPIN1b and IAA content were concentrated
in the cambium and adjacent xylem or phloem, and MdPIN1b protein was localized on
cell plasma membrane in onion epidermal cells transiently expressing 35S:MdPIN1b
GFP fusion protein. Interestingly, an MdPIN1b mutant allele in the promoter
region upstream of M9 exhibited decreased MdPIN1b expression compared to BC.
MdPIN1b over-expressing interstem in tobacco exhibited increased polar auxin
transport. It is proposed that natural allelic differences decreased promoter
activity is closely associated with lower MdPIN1b expression in the M9 interstem,
which might limit the basipetal transport of auxin, and in turn might contribute
to the dwarfing effect. Taken together, these results reveal allelic variation
underlying an important apple rootstock trait, and specifically a novel molecular
genetic mechanism underlying dwarfing mechanism.
PMID- 29340954
TI - The Cultural Epigenesis of Gender-Based Violence in Cambodia: Local and Buddhist
Perspectives.
AB - Almost one in four women in Cambodia is a victim of physical, emotional or sexual
violence. The study aims to provide a comprehensive understanding of the ways in
which Cambodians see its causes and effects and to identify and analyse the
cultural forces that underpin and shape its landscape. An ethnographic study was
carried out with 102 perpetrators and survivors of emotional, physical and sexual
violence against women and 228 key informants from the Buddhist and healing
sectors. Their views and experiences of it were recorded-the popular idioms
expressed and the symptoms of distress experienced by survivors and perpetrators.
From these results, the eight cultural forces, or cultural attractors, that are
seen to propel a person to violence were identified. Violence stemmed from
blighted endowment, or 'bad building' (salphamnaan min l?alphaalpha) determined
by deeds in a previous life (kam). Children with a vicious character (kmeen kaac
or dosa-carita) might grow to be abusers, and particular birthmarks on boys were
thought to be portents. Krupsiloneh, or mishap, especially when a female's
horoscope predicted a zodiac house on the descent (riesey), explained
vulnerability to violence and its timing. Astrological incompatibility (kuu kam)
was a risk factor. Lust, anger and ignorance, the 'Triple Poison', fuelled it.
'Entering the road to ruin' (apayamuk), including alcohol abuse, womanising and
gambling, triggered it. Confusion and loss of judgement (moha) led to moral
blindness (mo ban). These were the eight cultural attractors that shaped the
landscape of violence against women. The cultural epigenesis of violence against
women in Cambodia is an insight which can be used to build culturally responsive
interventions and strengthen the primary prevention of violence against women. An
understanding of the epigenesis of violence could strengthen the primary
prevention of violence against women.
PMID- 29340955
TI - Adult Atopic Dermatitis is Associated with Increased Aortic Stiffness.
PMID- 29340956
TI - Semi-Targeted Analysis of Complex Matrices by ESI FT-ICR MS or How an
Experimental Bias may be Used as an Analytical Tool.
AB - Ammonia is well suited to favor deprotonation process in electrospray ionization
mass spectrometry (ESI-MS) to increase the formation of [M - H]-. Nevertheless,
NH3 may react with carbonyl compounds (aldehyde, ketone) and bias the composition
description of the investigated sample. This is of significant importance in the
study of complex mixture such as oil or bio-oil. To assess the ability of primary
amines to form imines with carbonyl compounds during the ESI-MS process, two
aldehydes (vanillin and cinnamaldehyde) and two ketones (butyrophenone and
trihydroxyacetophenone) have been infused in an ESI source with ammonia and two
different amines (aniline and 3-chloronaniline). The (+) ESI-MS analyses have
demonstrated the formation of imine whatever the considered carbonyl compound and
the used primary amine, the structure of which was extensively studied by tandem
mass spectrometry. Thus, it has been established that the addition of ammonia, in
the solution infused in an ESI source, may alter the composition description of a
complex mixture and leads to misinterpretations due to the formation of imines.
Nevertheless, this experimental bias can be used to identify the carbonyl
compounds in a pyrolysis bio-oil. As we demonstrated, infusion of the bio-oil
with 3-chloroaniline in ESI source leads to specifically derivatized carbonyl
compounds. Thanks to their chlorine isotopic pattern and the high mass
measurement accuracy, (+) ESI Fourier transform ion cyclotron resonance mass
spectrometry (FT-ICR MS) unambiguously highlighted them from the numerous CxHyOz
bio-oil components. These results offer a new perspective into the detailed
molecular structure of complex mixtures such as bio-oils. Graphical Abstract ?.
PMID- 29340957
TI - Spontaneous Isomerization of Peptide Cation Radicals Following Electron Transfer
Dissociation Revealed by UV-Vis Photodissociation Action Spectroscopy.
AB - Peptide cation radicals of the z-type were produced by electron transfer
dissociation (ETD) of peptide dications and studied by UV-Vis photodissociation
(UVPD) action spectroscopy. Cation radicals containing the Asp (D), Asn (N), Glu
(E), and Gln (Q) residues were found to spontaneously isomerize by hydrogen atom
migrations upon ETD. Canonical N-terminal [z4 + H]+? fragment ion-radicals of the
R-C?H-CONH- type, initially formed by N-Calpha bond cleavage, were found to be
minor components of the stable ion fraction. Vibronically broadened UV-Vis
absorption spectra were calculated by time-dependent density functional theory
for several [?DAAR + H]+ isomers and used to assign structures to the action
spectra. The potential energy surface of [?DAAR + H]+ isomers was mapped by ab
initio and density functional theory calculations that revealed multiple
isomerization pathways by hydrogen atom migrations. The transition-state energies
for the isomerizations were found to be lower than the dissociation thresholds,
accounting for the isomerization in non-dissociating ions. The facile
isomerization in [?XAAR + H]+ ions (X = D, N, E, and Q) was attributed to low
energy intermediates having the radical defect in the side chain that can promote
hydrogen migration along backbone Calpha positions. A similar side-chain mediated
mechanism is suggested for the facile intermolecular hydrogen migration between
the c- and [z + H]?-ETD fragments containing Asp, Asn, Glu, and Gln residues.
Graphical Abstract ?.
PMID- 29340958
TI - Robert C. Dunbar (June 26, 1943-October 31, 2017).
PMID- 29340959
TI - Matrix Assisted and/or Laser Desorption Ionization Quadrupole Ion Trap Time-of
Flight Mass Spectrometry of WO3 Clusters Formation in Gas Phase. Nanodiamonds,
Fullerene, and Graphene Oxide Matrices.
AB - The formation of W x O y+?/-? clusters in the gas phase was studied by laser
desorption ionization (LDI) and matrix assisted laser desorption ionization
(MALDI) of solid WO3. LDI produced (WO3) n+ ?/- ? (n = 1-7) clusters. In MALDI,
when using nano-diamonds (NDs), graphene oxide (GO), or fullerene (C60) matrices,
higher mass clusters were generated. In addition to (WO3) n-? clusters, oxygen
rich or -deficient species were found in both LDI and MALDI (with the total
number of clusters exceeding one hundred ~ 137). This is the first time that such
matrices have been used for the generation of(WO3) n+?/-? clusters in the gas
phase, while new high mass clusters (WO3) n-? (n = 12-19) were also detected.
Graphical Abstract.
PMID- 29340960
TI - Higher levels of progranulin in cerebrospinal fluid of patients with lymphoma and
carcinoma with CNS metastasis.
AB - Assessing central nervous system (CNS) involvement in patients with lymphoma or
carcinoma is important in determining therapy and prognosis. Progranulin (PGRN)
is a secreted glycosylated protein with roles in cancer growth and survival; it
is highly expressed in aggressive cancer cell lines and specimens from many
cancer types. We examined PRGN levels by Enzyme Immuno-Assay (EIA) in
cerebrospinal fluid (CSF) samples from 230 patients, including 18 with lymphoma
[12 with CNS metastasis (CNS+); 6 without CNS metastasis (CNS-)], 21 with
carcinomas (10 CNS+; 11 CNS-), and 191 control patients with non-cancer
neurological diseases, and compared PRGN levels among these disease groups.
Median CSF PGRN levels in the CNS+ lymphoma group were significantly higher than
in the CNS- lymphoma and control non-cancer groups; and were also significantly
higher in the CNS+ carcinoma group than in the CNS- carcinoma and control groups,
except for patients with infectious neurological disorders. Receiver operating
characteristic curve analyses revealed that CSF PGRN levels distinguished CNS+
lymphoma from CNS- lymphoma and non-cancer neurological diseases [area under
curve (AUC): 0.969]; and distinguished CNS+ carcinomas from CNS- carcinomas and
non-cancer neurological diseases (AUC: 0.918). We report here, for the first
time, that CSF PGRN levels are higher in patients with CNS+ lymphoma and
carcinomas compared to corresponding CNS- diseases. This would imply that
measuring CSF PGRN levels could be used to monitor CNS+ lymphoma and metastasis.
PMID- 29340961
TI - Metabolic syndrome and its components among Korean submariners: a retrospective
cross-sectional study.
AB - PURPOSE: Metabolic syndrome (MetS) is a cluster of inter-related risk factors for
cardiovascular disease and diabetes. Although submariners tend to be exposed to
unhealthy environmental factors, such as a confined work environment, physical
inactivity, and circadian disruption, little is known regarding whether the risks
of MetS and its components are associated with submarine service. The present
study aimed to evaluate the risks of MetS and its components among submariners.
METHODS: A total of 5090 subjects (513 submariners and 4577 non-submariners) were
included in the present study. We calculated the age-standardized and age
specific prevalences of MetS. The associations between submarine service and the
risks of MetS and its components were evaluated using logistic regression
analysis after adjusting for age, service rank, and lifestyle factors. RESULTS:
The age-standardized prevalences of MetS were 17.6 and 15.1% among submariners
and non-submariners, respectively. Compared to non-submariners, submariners had
higher risks of MetS (odds ratio [OR] 1.31, 95% confidence interval [CI] 1.02,
1.68), low high-density lipoprotein cholesterol (OR 1.73, 95% CI 1.36, 2.20), and
impaired fasting glucose (OR 1.46, 95% CI 1.21, 1.76). When we stratified the
subjects according to physical activity, an increased risk of elevated blood
pressure associated with submarine service was evident only in the subgroup with
moderate or vigorous physical activity (P for interaction = 0.006). CONCLUSION:
Submariners had higher risks of MetS and some MetS components, compared to non
submariners. These findings suggest that special efforts are needed to prevent
and manage MetS among individuals who are expected to be exposed to submarine
environment.
PMID- 29340962
TI - Apoptotic and proliferative indexes in esophageal cancer: Predictors of response
to neoadjuvant therapy apoptosis and proliferation in esophageal cancer.
AB - Altered expression of the genes that control apoptosis and proliferation may
influence the response of cancer cells to cytotoxic agents. The primary aim of
this study was to determine the role of the novel an-tiapoptotic and cell cycle
gene, survivin, in apoptotsis and proliferation in esophageal cancer and to
evaluate whether the survivin, p53, and bcl-2 status were able to predict a
patient's response to neoadjuvant therapy. A total of 104 patients with
esophageal tumors were studied. Tumor tissue was immunostained for survivin, p53,
and bcl-2 proteins. Proliferative and apoptotic activity was measured using ki-67
immu-nohistochemical analysis and the TUNEL method, respectively. Forty-eight
patients whose pretreat-ment biopsies were analyzed received neoadjuvant
chemoradiation therapy or chemotherapy followed by surgery. Outcome was graded as
a complete response, a partial response, or no response according to the results
of histologic examination and CT imaging. Expression of survivin was found to
correlate significantly with the proliferative index but not the apoptotic index.
Patients who received neoadjuvant treatment were more likely to achieve a
complete response if their tumors had high proliferative activity, and p53
positive tumors were more likely to contain residual tumor after treatment. In
conclusion, survivin expression appears to foster proliferative activity in
esophageal cancer, and tumors with a high proliferative index or a functioning
p53 gene are more responsive to neoadjuvant chemoradiation therapy.
PMID- 29340963
TI - Interactions between drugs and geriatric syndromes in nursing home and home care:
results from Shelter and IBenC projects.
AB - AIM: Drugs may interact with geriatric syndromes by playing a role in the
continuation, recurrence or worsening of these conditions. Aim of this study is
to assess the prevalence of interactions between drugs and three common geriatric
syndromes (delirium, falls and urinary incontinence) among older adults in
nursing home and home care in Europe. METHODS: We performed a cross-sectional
multicenter study among 4023 nursing home residents participating in the Services
and Health for Elderly in Long-TERm care (Shelter) project and 1469 home care
patients participating in the Identifying best practices for care-dependent
elderly by Benchmarking Costs and outcomes of community care (IBenC) project.
Exposure to interactions between drugs and geriatric syndromes was assessed by
2015 Beers criteria. RESULTS: 790/4023 (19.6%) residents in the Shelter Project
and 179/1469 (12.2%) home care patients in the IBenC Project presented with one
or more drug interactions with geriatric syndromes. In the Shelter project,
288/373 (77.2%) residents experiencing a fall, 429/659 (65.1%) presenting with
delirium and 180/2765 (6.5%) with urinary incontinence were on one or more
interacting drugs. In the IBenC project, 78/172 (45.3%) participants experiencing
a fall, 80/182 (44.0%) presenting with delirium and 36/504 (7.1%) with urinary
incontinence were on one or more interacting drugs. CONCLUSION: Drug-geriatric
syndromes interactions are common in long-term care patients. Future studies and
interventions aimed at improving pharmacological prescription in the long-term
care setting should assess not only drug-drug and drug-disease interactions, but
also interactions involving geriatric syndromes.
PMID- 29340964
TI - Geriatric nutritional risk index as a simple tool for assessment of malnutrition
among geriatrics in Northwest of Iran: comparison with mini nutritional
assessment.
AB - BACKGROUND: Older people are more likely to develop nutritional problems and
timely diagnosis of malnutrition is crucial to prevent hazardous consequences
following poor nutrition. AIMS: To evaluate the efficacy of Geriatric Nutritional
Risk Index (GNRI) to assess nutritional status among non-hospitalized elderly,
compared to mini nutritional assessment (MNA) among Iranian seniors. METHODS: One
hundred and sixty-four subjects, aged >= 65 years old were recruited to our cross
sectional study from various districts of Tabriz (Tabriz, Iran). Anthropometric
and biochemical measurements were performed, short- and long-form MNAs and GNRI
were assessed in our study subjects. Sensitivity, specificity and predictive
values of the three indices, agreement between them, and their correlation with
anthropometric and biochemical parameters were evaluated. Receiver-operating
characteristic (ROC) curve analysis was performed to determine the optimal cut
off point for GNRI in our study population. RESULTS: GNRI had lower sensitivity
(50, 57%), but optimal specificity (94, 93%) and lower negative predictive value
(NPV; 68, 71%) compared to MNA-LF and MNA-SF, respectively. We found a moderate
agreement between GNRI and MNA-SF (K = 0.52) and MNA-LF (K = 0.46) scores.
Significant correlations were observed between re-categorized MNAs as well as
GNRI scores, and age, weight, MAC, CC, WC, albumin, and pre-albumin. The cut-off
point of 110.33 was obtained for GNRI, according to the ROC curve. CONCLUSIONS:
Although GNRI may not be an efficient tool for screening malnutrition due to its
lower sensitivity, it is moderately correlated with MNAs and also more useful
when limited funding needs to target the truly malnourished seniors.
PMID- 29340965
TI - Emotional and social characteristics of stroke patients with low verbal memory.
AB - BACKGROUND: Cognitive deficits, especially problems with memory observed after
stroke often coexist with patients' experience of difficulties in everyday life
situations. AIMS: The purposes of the study were to explore the relationships
between verbal memory, emotional functioning and social competence in stroke
patients, and to examine the emotional and social condition of stroke patients
with low verbal memory. METHODS: Ninety-five participants were assessed with the
Rey Auditory Verbal Learning Test, the Neuropsychology Behavior and Affect
Profile, and the Social Competency Questionnaire. The participants' relatives (N
= 95) also took part in the study evaluating patients' emotional and social
functioning. RESULTS: Stroke patients with low verbal memory had higher scores in
depression, indifference, and inappropriateness than the patients with normal
memory. They also obtained higher scores in the self-reported intimacy and lower
scores in objectively assessed social exposition than controls. DISCUSSION: It is
worth considering patients' relationships with relatives that evolve after
stroke, especially when the patients experience cognitive difficulties in gaining
new information. Collecting verbal information seems to be important for the
feeling of effectiveness in some dimensions of elders' social functioning.
CONCLUSIONS: Because the social engagement may be treated as protective factor in
the course of recovery we would recommend that during rehabilitation more
attention should be paid to emotional and social functioning of stroke patients
with low verbal memory.
PMID- 29340966
TI - Cannabinomimetric Lipids: From Natural Extract to Artificial Synthesis.
AB - Endocannabinoid system is related with various physiological and cognitive
processes including fertility, pregnancy, during pre- and postnatal development,
pain-sensation, mood, appetite, and memory. In the latest decades, an important
milestone concerning the endocannabinoid system was the discovery of the
existence of the cannabinoid receptors CB1 and CB2. Anandamide was the first
reported endogenous metabolite, which adjusted the release of some
neurotransmitters through binding to the CB1 or CB2 receptors. Then a series of
cannabinomimetric lipids were extracted from marine organisms, which possessed
similar structure with anandamide. This review will provide a short account about
cannabinomimetric lipids for their extraction and synthesis.
PMID- 29340967
TI - Testing the actual equivalence of automatically generated items.
AB - If the automatic item generation is used for generating test items, the question
of how the equivalence among different instances may be tested is fundamental to
assure an accurate assessment. In the present research, the question was dealt by
using the knowledge space theory framework. Two different ways of considering the
equivalence among instances are proposed: The former is at a deterministic level
and it requires that all the instances of an item template must belong to exactly
the same knowledge states; the latter adds a probabilistic level to the
deterministic one. The former type of equivalence can be modeled by using the
BLIM with a knowledge structure assuming equally informative instances; the
latter can be modeled by a constrained BLIM. This model assumes equality
constraints among the error parameters of the equivalent instances. An approach
is proposed for testing the equivalence among instances, which is based on a
series of model comparisons. A simulation study and an empirical application show
the viability of the approach.
PMID- 29340968
TI - A novel blink detection method based on pupillometry noise.
AB - Pupillometry (or the measurement of pupil size) is commonly used as an index of
cognitive load and arousal. Pupil size data are recorded using eyetracking
devices that provide an output containing pupil size at various points in time.
During blinks the eyetracking device loses track of the pupil, resulting in
missing values in the output file. The missing-sample time window is preceded and
followed by a sharp change in the recorded pupil size, due to the opening and
closing of the eyelids. This eyelid signal can create artificial effects if it is
not removed from the data. Thus, accurate detection of the onset and the offset
of blinks is necessary for pupil size analysis. Although there are several
approaches to detecting and removing blinks from the data, most of these
approaches do not remove the eyelid signal or can result in a relatively large
amount of data loss. The present work suggests a novel blink detection algorithm
based on the fluctuations that characterize pupil data. These fluctuations
("noise") result from measurement error produced by the eyetracker device. Our
algorithm finds the onset and offset of the blinks on the basis of this
fluctuation pattern and its distinctiveness from the eyelid signal. By comparing
our algorithm to three other common blink detection methods and to results from
two independent human raters, we demonstrate the effectiveness of our algorithm
in detecting blink onset and offset. The algorithm's code and example files for
processing multiple eye blinks are freely available for download (
https://osf.io/jyz43 ).
PMID- 29340969
TI - On the predictive validity of various corpus-based frequency norms in L2 English
lexical processing.
AB - The predictive validity of various corpus-based frequency norms in first-language
lexical processing has been intensively investigated in previous research, but
less attention has been paid to this issue in second-language (L2) processing. To
bridge the gap, in the present study we took English as a case in point and
compared the predictive power of a large set of corpus-based frequency norms for
the performance of an L2 English visual lexical decision task (LDT). Our results
showed that, in general, the frequency norms from SUBTLEX-US and WorldLex-Blog
tended to predict L2 performance better in reaction times, whereas the frequency
norms from corpora with a mixture of written and spoken genres (CELEX, WorldLex
Blog, BNC, ANC, and COCA) tended to predict L2 accuracy better. Although
replicated in both low- and high-proficiency L2 English learners, these patterns
were not exactly the same as those found in LDT data from native English
speakers. In addition, we only observed some limited advantages of the lemma
frequency and contextual diversity measures over the wordform frequency measure
in predicting L2 lexical processing. The results of the present study, especially
the detailed comparisons among the different corpora, provide methodological
implications for future L2 lexical research.
PMID- 29340970
TI - Ultrahigh temporal resolution of visual presentation using gaming monitors and G
Sync.
AB - Vision unfolds as an intricate pattern of information processing over time.
Studying vision and visual cognition therefore requires precise manipulations of
the timing of visual stimulus presentation. Although standard computer display
technologies offer great accuracy and precision of visual presentation, their
temporal resolution is limited. This limitation stems from the fact that the
presentation of rendered stimuli has to wait until the next refresh of the
computer screen. We present a novel method for presenting visual stimuli with
ultrahigh temporal resolution (<1 ms) on newly available gaming monitors. The
method capitalizes on the G-Sync technology, which allows for presenting stimuli
as soon as they have been rendered by the computer's graphics card, without
having to wait for the next screen refresh. We provide software implementations
in the three programming languages C++, Python (using PsychoPy2), and Matlab
(using Psychtoolbox3). For all implementations, we confirmed the ultrahigh
temporal resolution of visual presentation with external measurements by using a
photodiode. Moreover, a psychophysical experiment revealed that the ultrahigh
temporal resolution impacts on human visual performance. Specifically, observers'
object recognition performance improved over fine-grained increases of object
presentation duration in a theoretically predicted way. Taken together, the
present study shows that the G-Sync-based presentation method enables researchers
to investigate visual processes whose data patterns were concealed by the low
temporal resolution of previous technologies. Therefore, this new presentation
method may be a valuable tool for experimental psychologists and neuroscientists
studying vision and its temporal characteristics.
PMID- 29340971
TI - Denosumab or oral bisphosphonates in primary osteoporosis: a "real-life" study.
AB - PURPOSE: To compare the response to denosumab (DMAb) therapy with that of oral
bisphosphonate (BISPH) treatment in postmenopausal women with primary
osteoporosis (PO). METHODS: In this retrospective study, we compared data of 75
PO female patients treated for 24 months with DMab (DMAb Group, age 72.6 +/- 8.9
years) with those of 75 PO patients treated with oral bisphosphonates (BISPH
Group), matched for age, body mass index, femoral bone mineral density (BMD),
prevalent fragility fractures and familiar history of hip fracture. In all
subjects at baseline and after 24 months we assessed the calcium-phosphorous
metabolism parameters, BMD at lumbar spine (LS-BMD) and femoral neck (FN-BMD) by
dual X-ray absorptiometry and the morphometric vertebral fractures by radiograph.
The patients were considered inadequate responders in the presence of >= 2
incident fragility fractures and/or a decrease in BMD greater than the least
significant change (LS 2.8%, FN 5.9%). RESULTS: After 24 months, the DMab Group
showed a greater ALP decrease (- 22.8 +/- 18.2%), a higher LS-BMD and FN-BMD
increase (6.6 +/- 6.9 and 4.4 +/- 8.2%, respectively) and a lower number of
patients with an incident fracture (8%) and with an inadequate response (6.7%)
than BISPH Group (- 14.9 +/- 15.3, 2.5 +/- 4.3, 1.9 +/- 4.5, 21.3 and 22.7%,
respectively, p < 0.05 for all comparisons). The inadequate response was 4.5-fold
more likely in BISPH Group than in DMab one (p = 0.027), regardless of possible
confounders. CONCLUSIONS: In postmenopausal PO females, denosumab was more
effective than oral bisphosphonates in increasing BMD and reducing bone turnover
and the number of inadequate responder patients.
PMID- 29340972
TI - Presence of diabetes-specific autoimmunity in women with gestational diabetes
mellitus (GDM) predicts impaired glucose regulation at follow-up.
AB - PURPOSE: Gestational diabetes mellitus (GDM) is the most frequent complication of
pregnancy; around 10% of GDM cases may be determined by autoimmunity, and our
aims were to establish the role of autoimmunity in a population of Sardinian
women affected by GDM, to find predictive factors for autoimmune GDM, and to
determine type 1 diabetes (T1D) auto-antibodies (Aabs) together with glucose
tolerance after a mean 21.2 months of follow-up. METHODS: We consecutively
recruited 143 women affected by GDM and 60 without GDM; clinical data and
pregnancy outcomes were obtained by outpatient visit or phone recall. T1D auto
antibodies GADA, IA2-A, IAA, ZnT8-A were measured in the whole population at
baseline, and in the Aab-positive women at follow-up. RESULTS: The overall
prevalence of autoimmunity was 6.4% (13/203). No significant difference was found
in the prevalence of auto-antibodies between GDM (5.6%) and control (8.3%) women,
neither in antibody titres. Highest titres for GADA and ZnT8-A were observed in
the control group; no phenotypic factors were predictive for autoimmune GDM.
Diabetes-related autoantibodies were still present in all the GDM women at follow
up, and their presence was associated with a 2.65 (p < 0.0016) relative risk (RR)
of glucose impairment. CONCLUSION: We observed a low prevalence (5.6%) of
diabetes-related autoimmunity in our GDM cohort, consistent with the prevalence
reported in previous studies. It was not possible to uncover features predictive
of autoimmune GDM. However, given the significant risk of a persistent impaired
glycemic regulation at follow-up, it is advisable to control for glucose
tolerance in GDM women with diabetes-related autoimmunity.
PMID- 29340973
TI - Reference intervals for thyrotropin in an area of Northern Italy: the Pordenone
thyroid study (TRIPP).
AB - PURPOSE: Thyrotropin (TSH) is the most accurate marker of thyroid dysfunction in
the absence of pituitary or hypothalamic disease. Studies on TSH reference
intervals (RIs) showed wide inter-individual variability and prompted an intense
debate about the best estimation of TSH RIs. DESIGN: We performed a population
study on TSH RIs, using current data stored in the laboratory information system
(LIS), at the Hospital Department of Laboratory Medicine, Pordenone (Italy),
historically an area of mild-moderate iodine deficiency with a relatively high
goiter prevalence. METHODS: 136,650 individuals constituted the final sample. A
TSH immunoassay was performed on fasting serum samples with the Dimension Vista
1500 analyzer (Siemens Healthineers). We adopted the Kairisto's procedure to
analyze TSH data downloaded by the LIS, applying the indirect strategy for
deriving RIs. RESULTS: TSH RIs of the entire population were 0.32-3.36 mIU/L with
a distribution skewed towards higher values. RIs were 0.26-3.61 mIU/L for
females, and 0.32-3.01 mIU/L for males. Unlike other studies, TSH median levels
progressively decreased from 0-4 to 85-104 years in the overall population, both
in male and in female subgroups, showing an inverse correlation between TSH and
age in all groups. CONCLUSIONS: This study is the first to analyze a high
percentage (40%) of individuals from an ethnically homogenous Caucasian
population. The results obtained emphasize the opportunity to define the TSH RIs
according to age, gender and race, in addition to assay methods, and provide
further insight about the possible role of iodine status.
PMID- 29340974
TI - Inhibiting 6-phosphogluconate dehydrogenase selectively targets breast cancer
through AMPK activation.
AB - PURPOSE: 6-phosphogluconate dehydrogenase (6PGD), a key enzyme of the oxidative
pentose phosphate pathway, is involved in tumor growth and metabolism. Although
high 6PGD activity has been shown to be associated with poor prognosis, its role
and therapeutic value in breast cancer remain unknown. METHODS: The levels and
roles of 6PGD were analyzed in breast cancer cells and their normal counterparts.
The underlying mechanisms of 6PGD's roles are also analyzed. RESULTS: We found
that 6PGD is aberrantly activated in breast cancer as shown by its increased
transcriptional and translational levels as well as enzyme activity in breast
cancer tissues and cell lines compared to normal counterparts. Although similar
degree of enzyme activity inhibition was achieved in both breast cancer and
normal breast cells, 6PGD inhibition by siRNA-mediated knockdown or
pharmacological inhibitor physcion is more effective in inhibiting growth and
survival in breast cancer than normal breast cells. Moreover, inhibiting 6PGD
significantly sensitizes breast cancer response to chemotherapeutic agents in in
vitro cell culture system and in vivo xenograft breast cancer model. We further
show that 6PGD inhibition activates AMPK and its downstream substrate ACC1,
leading to reduction of ACC1 activity and lipid biosynthesis. AMPK depletion
significantly reverses the inhibitory effects of physcion in breast cancer cells,
confirming that 6PGD inhibition targets breast cancer cell via AMPK activation.
CONCLUSIONS: Our work provides experimental evidence on the association of 6PGD
with poor prognosis in breast cancer and suggests that 6PGD inhibition may
represent a potential therapeutic strategy to augment chemotherapy efficacy in
breast cancer.
PMID- 29340975
TI - Epidemiology of injuries in tennis players.
AB - PURPOSE OF REVIEW: To review the recent literature regarding the epidemiology of
tennis injuries at all levels of play, and to discuss recent findings in injury
surveillance by the Association of Tennis Professionals (ATP). RECENT FINDINGS:
Following the release of a consensus statement in 2009 calling for standardized
documentation and analysis of tennis-related injuries, multiple studies have been
published describing longitudinal injury incidences at Grand Slam tournaments and
the Davis Cup. Recent efforts by the ATP have further elucidated injury patterns
on tour. There have also been recent high-quality studies on injury trends among
collegiate and elite junior tennis players, bringing attention to musculoskeletal
injuries and systemic illnesses that young tennis players may be susceptible to.
Recent efforts in injury surveillance by the ATP and at the collegiate and junior
levels have highlighted injury trends that will help guide injury prevention
strategies at various levels of play.
PMID- 29340976
TI - Erratum to: Apoptotic and proliferative indexes in esophageal cancer: Predictors
of response to neoadjuvant therapy apoptosis and proliferation in esophageal
cancer.
PMID- 29340977
TI - New Strategies for Improving the Development and Performance of Amorphous Solid
Dispersions.
AB - The understanding of amorphous solid dispersions has grown significantly in the
past decade. This is evident from the number of approved commercial amorphous
solid dispersion products. While amorphous formulation is considered an enabling
technology, it has become the norm for formulating poorly soluble compounds.
Despite this success, improvements can still be made that enable early
development formulation decisions, to develop a rationale for selecting a
manufacturing process, to overcome degradation and phase separation during
processing, to help achieve physical stability during storage, and to optimize
dissolution behavior. The purpose of this literature review is to present
recently reported strategies for improving the development and performance of
ASDs. The benefits and limitations of each strategy as well as recent relevant
case studies will be presented in this review. The strategies are presented from
three different aspects: (a) prediction techniques that enable formulation
decisions, (b) manufacturing considerations that help produce physically and
chemically stable ASDs, and
PMID- 29340978
TI - Methotrexate Aspasomes Against Rheumatoid Arthritis: Optimized Hydrogel Loaded
Liposomal Formulation with In Vivo Evaluation in Wistar Rats.
AB - Aspasomes of methotrexate with antioxidant, ascorbyl palmitate, were developed
and optimized using factorial design by varying parameters such as lipid molar
ratio, drug to lipid molar ratio, and type of hydration buffer for transdermal
delivery for disease modifying activity in rheumatoid arthritis (RA). Aspasomes
were characterized by drug-excipients interaction, particle size analysis,
determination of zeta potential, entrapment efficiency, and surface properties.
The best formulation was loaded into hydrogel for evaluation of in vitro drug
release and tested in vivo against adjuvant induced arthritis model in wistar
rats, by assessing various physiological, biochemical, hematological, and
histopathological parameters. Optimized aspasome formulation exhibited smooth
surface with particle size 386.8 nm, high drug loading (19.41%), negative surface
potential, and controlled drug release in vitro over 24 h with a steady
permeation rate. Transdermal application of methotrexate-loaded aspasome hydrogel
for 12 days reduced rat paw diameter (21.25%), SGOT (40.43%), SGPT (54.75%),
TNFalpha (33.99%), IL beta (34.79%), cartilage damage (84.41%), inflammation
(82.37%), panus formation (84.38%), and bone resorption (80.52%) as compared to
arthritic control rats. Free methotrexate-treated group showed intermediate
effects. However, drug-free aspasome treatment did not show any effect. The
experimental results indicate a positive outcome in development of drug-loaded
therapeutically active carrier system which presents a non-invasive controlled
release transdermal formulation with good drug loading, drug permeation rate, and
having better disease modifications against RA than the free drug, thereby
providing a more attractive therapeutic strategy for rheumatoid disease
management.
PMID- 29340979
TI - Effect of Moisture Content of Chitin-Calcium Silicate on Rate of Degradation of
Cefotaxime Sodium.
AB - Assessment of incompatibilities between active pharmaceutical ingredient and
pharmaceutical excipients is an important part of preformulation studies. The
objective of the work was to assess the effect of moisture content of chitin
calcium silicate of two size ranges (two specific surface areas) on the rate of
degradation of cefotaxime sodium. The surface area of the excipient was
determined using adsorption method. The effect of moisture content of a given
size range on the stability of the drug was determined at 40 degrees C in the
solid state. The moisture content was determined at the beginning and the end of
the kinetic study using TGA. The degradation in solution was studied for
comparison. Increasing the moisture content of the excipient of size range 63-180
MUm (surface area 7.2 m2/g) from 3.88 to 8.06% increased the rate of degradation
of the drug more than two times (from 0.0317 to 0.0718 h-1). While an opposite
trend was observed for the excipient of size range < 63 MUm (surface area 55.4
m2/g). The rate of degradation at moisture content < 3% was 0.4547 h-1, almost
two times higher than that (0.2594 h-1) at moisture content of 8.54%, and the
degradation in solid state at both moisture contents was higher than that in
solution (0.0871 h-1). In conclusion, the rate of degradation in solid should be
studied taking into consideration the specific surface area and moisture content
of the excipient at the storage condition and it may be higher than that in
solution.
PMID- 29340980
TI - Facile Synthesis of Chitosan Capped Mesoporous Silica Nanoparticles: A pH
Responsive Smart Delivery Platform for Raloxifene Hydrochloride.
AB - An encapsulation of model drug raloxifene hydrochloride (RAL) inside the chitosan
decorated pH responsive mesoporous system has a greater potential for
accumulating in the tumor cells. The present study involves synthesis of surface
modified mesoporous silica nanoparticles (MSN) with the aim of achieving pH
sensitive drug delivery system. A silanol skeleton of MSN has been productively
modified to amine intermediate which served as a firm platform to adapt chitosan
grafted assembly and systematically evaluated. RAL incorporation inside the
featured mesopores was performed employing novel immersion solvent evaporation
methodology and evaluated further. The pH responsive behavior of formulated nano
framework was studied at three different pH of a phosphate buffer saline
individually. The in vitro cell viability assay on MCF-7 breast carcinoma cells
was performed in time and concentration dependent manner. Finally, the hemolysis
assay of designed nanoparticle was accomplished to envisage the
hemocompatibility. The outcome of characterization details unveiled a perfect 2D
hexagonal spherical structure gifted with higher surface area and optimum pore
size for designed nanoparticles. The higher percentage grafting of amine and
chitosan residue, i.e., 4.01 and 28.51% respectively along with 31.89 and 33.57%
RAL loading efficiency made MSNs more attractive and applicable. Eventually, in
vitro release study exhibited higher RAL release in acidic media for extended
time periods confirming successful formation of pH responsive nanoparticle having
controlled release property. Conclusively potential of designed nanosystem to
serve efficient anti-cancer remedy was confirmed by superior behaviour of
chitosan grafted MSN towards MCF-7 cells with supreme hemocompatibility.
PMID- 29340981
TI - Nanolipid Gel of an Antimycotic Drug for Treating Vulvovaginal Candidiasis
Development and Evaluation.
AB - This paper focuses on the development and evaluation of mucoadhesive vaginal gel
of fluconazole using nanolipid carriers to enhance tissue deposition in treating
vulvovaginal candidiasis. Treatment of vulvovaginal candidiasis includes
antimycotic agents prescribed for 1 to 7 days or longer, in relapse either orally
or topically. The delivery of fluconazole as nanolipid carriers in vaginal gel
can be proposed as suitable alternative to the existing conventional formulations
to improve the patient acceptability, compliance and localized drug action. The
nanolipid carriers of fluconazole were prepared by phase inversion temperature
technique and incorporated into Carbopol 974P as gelling polymer. GRAS excipients
selected and optimized were Precirol ATO 5, oleic acid and Kolliphor RH 40 to
produce nanolipid dispersions. Stable nanolipid dispersions were developed using
sodium dodecyl sulfate as the charge inducer. The optimized nanolipid dispersion
of fluconazole had particle size, polydispersity index and zeta potential value
of 158.33 +/- 2.55 nm, 0.278 +/- 0.003 and - 27.33 +/- 0.40 mV, respectively and
the average entrapment of fluconazole in the lipid carriers was found to be 67.24
+/- 0.87%. The optimized vaginal gel had satisfactory mucoadhesive strength and
rheological properties to facilitate vaginal application. The fluconazole release
from the gel was sustained showing 30.69 +/- 1.02% drug deposition in the porcine
vaginal mucosa at the end of 8 h with improved antifungal activity against
Candida albicans during well diffusion studies. The optimized gel was non
irritant to the vaginal mucosa of female Wistar rats with no signs of erythema or
edema.
PMID- 29340982
TI - Controlled Release of the Nimodipine-Loaded Self-Microemulsion Osmotic Pump
Capsules: Development and Characterization.
AB - The present study was intended to develop a controlled released osmotic pump
capsule based on Nimodipine (NM)-loaded self-microemulsifying drug delivery
systems (SMEDDSs) in order to improve the low oral bioavailability of NM. To
optimize the NM-loaded SMEDDS composition, the experiments of NM solubility in
different oils, the pseudo-ternary phase diagram experiments and the different
drug loading experiments were conducted in the preliminary screening studies.
Controlled release of NM required an osmotic pump capsule comprising a coated
semi-permeable capsule shell, plasticizer, and pore-forming agent. NM release
follows zero-order kinetics after oral administration. Polyethylene glycol
content, used as a pore-forming agent, coating mass, and drug release orifice
size were key factors affecting drug release behavior according to the single
methods and were optimized through response surface methodology. The NM-loaded
SMEDDS droplet size and the 1H NMR mass spectrogram of the novel capsule were
determined. The droplet size of the reconstituted microemulsion was 39.9 nm and
1H NMR analysis showed NM dissolution in the microemulsion. The dissolution test
performed on three batches of NM-SMEDDS capsules-prepared using optimal
preparation methods-indicated the capsule to deliver a qualified drug delivery
with a zero-order release rate. The results demonstrated that NM-loaded SMEDDSs
were successfully developed and displayed a qualified release rate in vitro.
PMID- 29340983
TI - 18F-FDG PET/CT-imaging of left ventricular assist device infection: a
retrospective quantitative intrapatient analysis.
AB - BACKGROUND: Despite the use of 18F-fluorodeoxyglucose (18F-FDG) positron emission
tomography/computed tomography (PET/CT), diagnosis of a driveline infection in
ventricular assist device (LVAD) recipients remains challenging. Our aim was to
evaluate the potential of a baseline 18F-FDG PET/CT (prior to an infection) for
the diagnosis of an LVAD-related infection. METHODS: We retrospectively selected
all LVAD recipients who had undergone two consecutive whole-body 18F-FDG PET/CT
examinations between January 2010 and December 2016. PET/CT was analyzed
qualitatively (uptake pattern) and semi-quantitatively (SUVmax and ?SUVmax).
SUVmax was measured and compared in five distinctive volumes of interest along
the LVAD driveline. An SUVmax threshold was calculated. Final diagnosis was made
by clinical examination, microbiological parameters, and molecular imaging.
RESULTS: Thirty patients were enrolled (mean age 54 +/- 12 years; 26 male). Mean
difference in SUVmax for all five positions between the first and the second
PET/CT along the driveline was significantly higher in patients with an LVAD
related infection (mean ?SUVmax = 4.38 +/- 1.44) compared to those without a
driveline infection (mean ?SUVmax = 0.03 +/- 0.43), P < 0.05. Applying ROC
analysis, an SUVmax threshold of 3.88 resulted in a sensitivity and specificity
of 100%, respectively. There were three distinctive uptake patterns in patients
with a driveline infection. CONCLUSION: PET/CT diagnosis in the context of an
LVAD-related infection can be improved by comparison to a baseline examination
using a distinctive SUVmax threshold.
PMID- 29340984
TI - Exercise-induced ST elevation with minimal ischemia by perfusion imaging.
PMID- 29340985
TI - The mystery poor prognosticator! Pharmacologic stress MPI prevalence and
predictors: Insights from the Middle East.
PMID- 29340986
TI - Comparison of maximal Rubidium-82 activities for myocardial blood flow
quantification between digital and conventional PET systems.
AB - BACKGROUND: PET-based myocardial blood flow (MBF) quantification can be
inaccurate when using high tracer activities. Our aim was to derive the maximal
Rubidium-82 activity for MBF assessment using a new digital PET system and
compare the results with conventional analog systems. METHODS: 1.8 GBq Rubidium
82 was injected into the cardiac insert of an anthropomorphic torso phantom. Data
were acquired for 10 min using an Ingenuity TF (Philips Healthcare), Discovery
690 (D690, GE Healthcare), and digital PET prototype system (Philips Healthcare).
The dynamic ranges, defined as the maximal measured activity in the reconstructed
images deviating < 10% from the true present activity, were determined in all
scans. RESULTS: The dynamic ranges were 312 MBq for Ingenuity TF, 650 MBq for
D690, and 654 MBq for digital PET prototype. CONCLUSIONS: The maximal Rb-82
activity for MBF assessment using digital PET prototype is higher than that for
its analog counterpart (Ingenuity TF), but seems comparable to the D690.
PMID- 29340987
TI - Lost in quantification...: The influence of different software packages on flow
quantification measures.
PMID- 29340988
TI - Interventricular septum involvement with complete atrioventricular block as first
manifestation in Takayasu arteritis.
PMID- 29340989
TI - Gated SPECT myocardial perfusion imaging with cadmium-zinc-telluride detectors
allows real-time assessment of dobutamine-stress-induced wall motion
abnormalities.
AB - BACKGROUND: Left ventricular (LV) ejection fraction (EF) during high dobutamine
stress (HD) by real-time gated-SPECT myocardial perfusion imaging (MPI) on a
cadmium-zinc-telluride (CZT) gamma camera was validated versus cardiac magnetic
resonance imaging (CMR). METHODS AND RESULTS: After injecting 99mTc-tetrofosmin
(320 MBq) in 50 patients (mean age 64 +/- 11 years), EF at rest and post-stress
as well as relevant changes in EF at HD (DeltaEF >= 5%) were assessed. CZT and
CMR rest EF values yielded an excellent correlation and agreement (r = 0.96; P <
0.001; Bland-Altman limits of agreement (BA): + 0 to 14.8%). HD EF acquisition
was feasible using CZT and correlated better to HD CMR EF than did post-stress
CZT EF (r = 0.85 vs 0.76, respectively, all P < 0.001). Agreement in DeltaEF
detection between HD CMR and immediate post-stress CZT (reflecting standard
acquisition using conventional SPECT camera unable to scan during stress) was
45%, while this increased to 85% with real-time HD CZT scan. CONCLUSION: Real
time ultrafast dobutamine gated-SPECT MPI with a CZT device is feasible and
provides accurate measurements of HD LV performance.
PMID- 29340990
TI - Role of myocardial perfusion scintigraphy in octogenarians: Time for reappraisal?
PMID- 29340991
TI - Neoadjuvant Chemotherapy for Hypopharyngeal Squamous Cell Carcinoma and
Personalized Medicine in Head and Neck Cancer.
PMID- 29340992
TI - Prospective Comparative Study of Laparoscopic Narrow Band Imaging (NBI) Versus
Standard Imaging in Gynecologic Oncology.
AB - BACKGROUND: Narrow band imaging (NBI) is an optic filtration enhancement for
endoscopy that uses two wavelengths of light (415 and 540 nm) to highlight
superficial microvascular patterns. It has been successfully utilized to improve
identification of lesions with abnormal vasculature, which is associated with
endometriosis and endometrial cancer. Case studies suggest it may also facilitate
surgical staging of gynecologic cancer, which is critical in determining
appropriate adjuvant therapies. A technology that enhances the ability to
identify metastatic disease during minimally invasive surgery (MIS) could make an
important difference in patient outcomes. METHODS: A prospective comparative
study was conducted to evaluate patients with clinical indication for diagnostic
or operative laparoscopy. All received white light imaging followed by NBI during
the same procedure. Suspicious lesions were examined and photographed, using both
modalities, before excision. The two techniques were compared. Positive
predictive value, negative predictive value, and diagnostic accuracy in
identifying histologically confirmed metastatic lesions were assessed, using
appropriate statistical methods. RESULTS: Of 124 patients enrolled in the study,
94 were evaluable; 30 did not undergo MIS and were therefore excluded. A
significantly higher number of peritoneal abnormalities were identified with NBI
versus white light imaging (P = 0.0239). However, no statistically significant
difference (P = 0.18, patient level) was observed in identification of
histologically confirmed metastatic disease. CONCLUSIONS: NBI imaging provides a
unique contrast between peritoneal surface and microvascular patterns. However,
the results of this study suggest that NBI-enhanced laparoscopy does not provide
superior detection of peritoneal surface malignancy compared with standard white
light high-definition laparoscopy.
PMID- 29340993
TI - Laparoscopic-Assisted Modified Intersphincter Resection for Ultralow Rectal
Cancer.
AB - BACKGROUND: Intersphincter resection (ISR) is considered to be a superior
technique offering sphincter preservation in patients with ultralow rectal
cancer.1 Because high-definition laparoscopy offers wider and clearer vision into
the narrow pelvic cavity and intersphincteric space, ISR has been further
refined.2 However, functional outcome after ISR has not been optimal. More than
half of patients receiving ISR suffer partial or even complete anal
incontinence.3 We therefore propose a laparoscopic-assisted modified ISR, with
the aim of improving sphincter function following ISR. METHODS: The video
describes the technique for performing such laparoscopic-assisted modified ISR in
a 62-year-old woman with ultralow rectal cancer (3 cm from anal verge).
Preoperative staging by endorectal ultrasound and pelvic magnetic resonance
imaging revealed stage I rectal cancer (cT2N0M0). The operation consisted of an
abdominal and a perineal phase. The abdominal phase routinely involved colonic
mobilization with high ligation of inferior mesenteric vessels, total mesorectal
excision (TME), as well as transabdominal intersphincteric dissection. The
procedure for laparoscopic TME was performed according to our published method.4
Along the TME dissection plane, the puborectalis could be reached and the
intersphincteric space was entered posterolaterally. The hiatal ligament at the
posterior side of the rectum was transected afterwards. The dissection of the
intersphincteric space was continued caudally at the anterior side of the rectum.
The distal bowel wall was mobilized for 2 cm from the lower edge of the tumor to
obtain adequate distal margin. At this point, circular dissection of the
intersphincteric space was completed. After the abdominal phase, perineal
dissection was performed with wide exposure by use of a hooked self-retaining
retractor. The lower margin of the tumor was identified under direct vision. We
developed a modified ISR technique. Resection of the mucosa and internal
sphincter was initiated 2 cm distal to the lower edge of the tumor at the tumor
side to obtain the necessary distal margin. Meanwhile, at the opposite side of
the tumor, the resection line was just above the dentate line so that partial
dentate line could be preserved. After removal of the specimen en bloc per anus,
the pelvic cavity was generously irrigated with diluted povidone iodine
solutions. The distal margin of the specimen was then examined by frozen section
for presence of cancer. If clear, coloanal anastomosis was performed using a
handsewn technique. The colon was rotated 90 degrees and anastomosed to the anal
canal with interrupted absorbable 3-0 sutures. Finally, a pelvic suction drain
was placed, and a temporary diverting stoma made in the terminal ileum. RESULTS:
There were no intraoperative complications. The operating time was 180 min. Blood
loss was 50 mL. The distal margin was clear, and the final pathology was pT2N0M0.
The patient underwent an uneventful recovery. She began sphincter-strengthening
exercises 2 weeks after surgery. The stoma was closed after examinations 3 months
later. No local recurrence or distant metastasis was found. At 12-month follow
up, in terms of sphincteric function, the patient was continent to solids,
liquids, and flatus. CONCLUSIONS: Laparoscopic-assisted modified intersphincter
resection for ultralow rectal cancer is safe and feasible. This technique should
be considered whenever possible as a means to offer sphincter preservation and
improve sphincter function in patients with ultralow rectal cancer.
PMID- 29340994
TI - Erratum to: Detection of Ultrafine Anaphase Bridges.
PMID- 29340995
TI - Is bacteremia the decisive factor for the duration of antimicrobial therapy in
bacteremic urinary tract infections?
PMID- 29340996
TI - Recent advances in the development of polycyclic skeletons via Ugi reaction
cascades.
AB - Isocyanide-based multicomponent reactions are among the most powerful synthetic
tools available. Particularly, the isocyanide-based Ugi reaction can allow rapid
preparation of [Formula: see text]-aminoacyl amide derivatives and
polyazaheterocycles with extensive pharmaceutical applications. Moreover, bridged
polyazaheterocycles, including one or more quaternary carbon centers, can be
constructed via the Ugi cascade reaction in a few steps. This review will
emphasize synthesis and bioactivities of bridged compounds with quaternary
centers constructed through Ugi cascade reactions.
PMID- 29340998
TI - On pacing trials while scanning brain hemodynamics: The case of the SNARC effect.
AB - Experimental designs used to describe psychological effects on overt human
behavior are seldom suited to localize their corresponding neural substrates
based on the analysis of stimulus-evoked brain hemodynamic responses. This is
because stimuli in behavioral studies are usually separated by intertrial
intervals (ITIs) in the order of 1 second or so following a behavioral response,
which is notoriously too brief a time to detect a corresponding hemodynamic
response. In fact, a solution commonly adopted in neuroimaging studies is to
prolong the ITI up to several seconds. In doing so, the consequences of ITI
variations between behavioral and neuroimaging design variants are either
benignly neglected or explicitly assumed to be negligible. Here, we provide a
systematic investigation of the consequence of manipulating ITI in a design
optimized to study a well-established and highly replicable psychological
phenomenon-the spatial numerical association of response codes (SNARC). The
present exploration encompassed standard estimates of the SNARC effect (i.e., on
reaction times and accuracy), estimates of ITI effects on the emotional state of
participants before and after performing the SNARC task, as well as the degree of
perceived task difficulty. The results showed that, in striking contrast to the
common wisdom about the nil role of ITI, the substantial number of parametric
differences observed between the two ITI conditions suggests that ITI plays a
critical role in shaping the meaning of hemodynamic correlate of a psychological,
at least the SNARC, effect.
PMID- 29340999
TI - Introduction to MRI Physics.
AB - Magnetic resonance imaging (MRI) is an imaging technique derived from
radiofrequency (RF) signals of proton that are magnetized by a strong magnetic
field. These protons typically originate from water, fat, or metabolites. The
application of RF pulses is used to excite the magnetization, whereas pulsed
magnetic field gradients are used to provide spatial localization. This chapter
describes the fundamental principles giving rise to MR images. Furthermore, the
connection between relaxation and image contrast is discussed.
PMID- 29340997
TI - Immunohistochemical Biomarkers of Mesenchymal Neoplasms in Endocrine Organs:
Diagnostic Pitfalls and Recent Discoveries.
AB - Mesenchymal neoplasms rarely present in or adjacent to endocrine organs. In this
context, the recognition of these rare tumor types can be challenging, with
significant potential for misdiagnosis as sarcomatoid carcinomas (i.e.,
anaplastic thyroid carcinoma and sarcomatoid adrenal cortical carcinoma) or
neuroendocrine carcinomas, depending upon the dominant histologic patterns. In
this review, we address potential pitfalls in diagnosing selected mesenchymal
neoplasms arising within or near endocrine organs, including dedifferentiated
liposarcoma, synovial sarcoma, angiosarcoma, PEComa, proximal-type epithelioid
sarcoma, Ewing sarcoma, and neuroblastoma. For each of these tumor types, we
review clinical and pathologic features, histologic clues to distinguish them
from endocrine neoplasms, and recently developed immunohistochemical markers that
can be particularly useful for establishing the correct diagnosis.
PMID- 29341000
TI - Basic Pulse Sequences in Magnetic Resonance Imaging.
AB - Magnetic resonance images are obtained by a combination of different
radiofrequency pulses and gradient waveforms applied to the subject inside a
magnetic field. There are multiple pulse sequences used in clinical and
preclinical studies adjusted to whatever physician or researches want to analyze,
from basic anatomic images to accurate diagnostic techniques as diffusion,
perfusion, or functional imaging. In this chapter, we present the most used
radiofrequency pulse combinations of the two groups of sequences available in
magnetic resonance imaging: spin-echo and gradient-echo sequences.
PMID- 29341001
TI - Dynamic Susceptibility Contrast MRI in Small Animals.
AB - The use of magnetic resonance imaging (MRI) for studying the cerebral perfusion
mechanisms is well proved and contrasted in the clinical and research setups.
This methodology is a promising tool in assessing numerous brain diseases like
intracranial tumors, neurodegeneration processes, mental disorders, injuries and
so on. In the preclinical environment, perfusion MRI offers a powerful resource
for characterizing pathological models and specially identifying biomarkers to
monitor the illness and validate the efficacy of therapeutical approaches. This
chapter presents the theoretical bases and experimental protocols of dynamic
susceptibility contrast MRI acquisitions for developing perfusion MRI studies in
small animals.
PMID- 29341002
TI - Preclinical Arterial Spin Labeling Measurement of Cerebral Blood Flow.
AB - Magnetic resonance imaging has been utilized as a quantitative and noninvasive
method to image blood flow. Arterial spin labeling (ASL) is an MRI technique that
images blood flow using arterial blood water as an endogenous tracer. Herein we
describe the use of ASL to measure cerebral blood flow completely noninvasively
in rodents, including methods, analysis, and important considerations when
utilizing this technique.
PMID- 29341003
TI - Dynamic Contrast-Enhanced MRI.
AB - Dynamic contrast-enhanced MRI in pre-clinical imaging allows the in-vivo
monitoring of vascular, physiological properties in normal and diseased tissue.
There is considerable variation in the methods employed owing to the different
questions that can be asked and answered about the physiologic alterations as
well as morphologic changes in tissue. Here we review the typical decisions in
the design and execution of a dynamic contrast-enhanced MRI study in mice
although the findings can easily be transferred to other species. Emphasis is
placed on highlighting the many pitfalls that wait for the unaware pre-clinical
MRI practitioner and that go often unmentioned in the abundant literature dealing
with dynamic contrast-enhanced MRI in animal models.
PMID- 29341004
TI - Diffusion-Weighted Magnetic Resonance Imaging.
AB - Magnetic resonance imaging (MRI) is a technique based on the contents and
relaxation features of water in tissues. In basic MRI sequences, diffusion
phenomenon of water molecules is not taken into account although it has a notable
influence in the relaxation times, and therefore in the signal intensity of
images. In fact, MRI techniques that take advantage of water diffusion have
experienced a huge development in last years. Diffusion-weighted imaging (DWI)
has spectacularly evolved reaching nowadays a great impact both in clinical and
preclinical imaging-especially in the neuroimaging field-and in basic research.
We present here a protocol to perform DWI studies in a high-field preclinical
setup.
PMID- 29341005
TI - Diffusion Tensor Imaging (DTI).
AB - Diffusion Tensor Imaging is an MRI technique that allows in vivo noninvasive
measurement of the translational motion of water, providing information about its
anisotropy (or lack of it) in different tissues. DTI has been commonly used to
quantitatively measure the integrity of tissues which may be compromised by
neurological disease, such as white matter tracks of the brain, which normally
impart significant anisotropy to water motion in healthy brains. However, this
anisotropic effect is diminished when axonal or neuronal damage is present. This
chapter describes a standard protocol for DTI data acquisition in preclinical
studies.
PMID- 29341006
TI - Mapping Functional Connectivity in the Rodent Brain Using Electric-Stimulation
fMRI.
AB - Since its discovery in the early 90s, BOLD signal-based functional Magnetic
Resonance Imaging (fMRI) has become a fundamental technique for the study of
brain activity in basic and clinical research. Functional MRI signals provide an
indirect but robust and quantitative readout of brain activity through the tight
coupling between cerebral blood flow and neuronal activation, the so-called
neurovascular coupling. Combined with experimental techniques only available in
animal models, such as intracerebral micro-stimulation, optogenetics or
pharmacogenetics, provides a powerful framework to investigate the impact of
specific circuit manipulations on overall brain dynamics. The purpose of this
chapter is to provide a comprehensive protocol to measure brain activity using
fMRI with intracerebral electric micro-stimulation in murine models. Preclinical
research (especially in rodents) opens the door to very sophisticated and
informative experiments, but at the same time imposes important constrains (i.e.,
anesthetics, translatability), some of which will be addressed here.
PMID- 29341007
TI - Functional Diffusion Magnetic Resonance Imaging.
AB - Functional diffusion magnetic resonance imaging (fDMRI) is a noninvasive
technique that allows elucidating physiological and anatomical changes at a
microscopic scale by detection of water molecular displacements in tissue
structures. These displacements likely reflect microstructural changes associated
with neuronal or glial cells activation. In this chapter, we will describe the
physical and biological concepts of fDMRI and how images of brain activation can
be acquired in a preclinical setup.
PMID- 29341008
TI - In Vivo 1H Magnetic Resonance Spectroscopy.
AB - In vivo Magnetic Resonance Spectroscopy (MRS) allows the non-invasive detection
and quantification of a number of metabolites from localized volumes within a
living organism. MRS localization techniques can be divided into two main groups,
single voxel and multi-voxel. Single voxel techniques provide the metabolic
profile from a specific small volume, whereas multi-voxel techniques are used to
obtain the spatial distribution of metabolites throughout a large volume
subdivided into small contiguous voxels. This chapter describes standard
protocols for the acquisition and processing of in vivo single voxel1H MRS data
from the rodent brain.
PMID- 29341009
TI - In Vivo Heteronuclear Magnetic Resonance Spectroscopy.
AB - Magnetic Resonance Spectroscopy is a technique that has the capability of
measuring metabolites in vivo and, in appropriate conditions, to infer its
metabolic rates. The success of MRS depends a lot on its sensitivity, which
limits the usage of X-nuclei MRS. However, technological developments and
refinements in methods have made in vivo heteronuclear MRS possible in humans and
in small animals. This chapter provides detailed descriptions of the main
procedures needed to perform successful in vivo heteronuclear MRS experiments,
with a particular focus on experimental setup in 13C MRS experiments in rodents.
PMID- 29341010
TI - 1H Spectroscopic Imaging of the Rodent Brain.
AB - Proton MR spectroscopic imaging (MRSI) can provide a variety of "molecular
images" from animal models of human disease, which are useful for different
research purposes. This chapter describes a protocol for in vivo acquisition and
analysis of MRSI data from the rodent brain.
PMID- 29341011
TI - Susceptibility Weighted MRI in Rodents at 9.4 T.
AB - Susceptibility Weighted Imaging (SWI) is an established part of the clinical
neuroimaging toolbox and, since its inception, has also successfully been used in
various preclinical studies. Exploiting the effect of variations of magnetic
susceptibility between different tissues on the externally applied, static,
homogeneous magnetic field, the method visualizes venous vasculature, hemorrhages
and blood degradation products, calcifications, and tissue iron deposits. The
chapter describes in vivo and ex vivo protocols for preclinical SWI in rodents.
PMID- 29341012
TI - Biomedical 19F MRI Using Perfluorocarbons.
AB - Background-free fluorine (19F) MR imaging exhibits an excellent degree of
specificity, and facilitates among others the in vivo visualization of
inflammatory processes. Merging19F MR images with morphologically matching1H MR
images enables the exact anatomic localization of the observed19F signal.
Biochemically inert nanoemulsions of perfluorocarbons, which are known to be
taken up by the macrophage/monocyte system, are widely used as contrast agents
for preclinical applications. Herein, the most common protocols are described to
obtain high-resolution and artifact-free19F MR images even for compounds with
complex19F MR spectra. In addition, we report on the utilization of
perfluorocarbons with individual spectral identities and targeting approaches to
specifically visualize thrombi by19F MRI.
PMID- 29341013
TI - Rodent Abdominal Adipose Tissue Imaging by MR.
AB - Rodents including rats and mice are important models to study obesity, diabetes,
and metabolic syndrome in a preclinical setting. Translational and longitudinal
imaging of these rodents permit investigation of metabolic diseases and
identification of imaging biomarkers suitable for clinical translation. Here we
describe the imaging protocols for achieving quantitative abdominal imaging in
small animals followed by segmentation and quantification of fat volumes.
PMID- 29341014
TI - Cardiac MRI in Small Animals.
AB - Cardiac magnetic resonance (MR) imaging of mice is a valuable tool for the
precise in vivo diagnosis and prognosis of heart defects. This detailed protocol
describes the method of cardiac MR imaging in mice step by step. A series of MR
images captures the contractile function of the mouse heart and post-processing
of the image data yields morphometric parameters (myocardial mass, myocardial
wall thickness, ventricular end-systolic and end-diastolic volume) as well as
functional parameters (stroke volume and ejection fraction). This protocol may
also serve as a starting point for MR imaging of rats, by using larger image
dimensions (field-of-view) and MR hardware suitable for larger animals.
PMID- 29341015
TI - In Utero MRI of Mouse Embryos.
AB - Genetically engineered mouse models are used extensively as models of human
development and developmental diseases. Conventional histological approaches are
static and two-dimensional, and do not provide a full understanding of the
dynamic, spatiotemporal changes in developing mouse embryos. Magnetic resonance
imaging (MRI) offers a noninvasive and longitudinal approach for three
dimensional in utero imaging of normal and mutant mouse embryos. In this chapter,
we describe MRI approaches that have been developed for imaging the living
embryonic mouse brain and vasculature. Details are provided on the animal
preparation and setup, MRI equipment, acquisition and reconstruction methods that
have been found to be most useful for in utero MRI, including examples of
applications to fetal mouse neuroimaging.
PMID- 29341016
TI - Oxygenation Imaging by Nuclear Magnetic Resonance Methods.
AB - Oxygen monitoring is a topic of exhaustive research due to its central role in
many biological processes, from energy metabolism to gene regulation. The ability
to monitor in vivo the physiological distribution and the dynamics of oxygen from
subcellular to macroscopic levels is a prerequisite to better understand the
mechanisms associated with both normal and disease states (cancer,
neurodegeneration, stroke, etc.). This chapter focuses on magnetic resonance
imaging (MRI) based techniques to assess oxygenation in vivo. The first
methodology uses injected fluorinated agents to provide quantitative pO2
measurements with high precision and suitable spatial and temporal resolution for
many applications. The second method exploits changes in endogenous contrasts,
i.e., deoxyhemoglobin and oxygen molecules through measurements of T 2* and T 1,
in response to an intervention to qualitatively evaluate hypoxia and its
potential modulation.
PMID- 29341017
TI - Molecular Magnetic Resonance Imaging (mMRI).
AB - Molecular magnetic resonance imaging (mMRI) enables the detection of a protein of
interest in vivo, in a noninvasive manner. The general concept of mMRI is to
target a contrast agent to a protein of interest, and to perform a contrast
sensitive MRI sequence. Typically, contrast agents are made of a "contrastophore"
(the part of the construct responsible for the contrast on the images) and a
targeting moiety ("pharmacophore"). Recently, the development of a new family of
contrastophore carrying a high payload of iron oxide (micro-sized particles of
iron oxide, MPIO) has led to a dramatic increase in the sensitivity of mMRI.
Here, we describe the production of targeted MPIO using commercially available
reagents and the MRI protocols to allow their detection in vivo.
PMID- 29341018
TI - Magnetic Resonance Spectroscopy Studies of Mouse Models of Cancer.
AB - Magnetic resonance spectroscopy (MRS) or spectroscopic imaging (MRSI) enables the
detection of metabolites, amino acids, and lipids, among other biomolecules, in
tumors of live mouse models of cancer. Tumor-bearing mice are anesthetized by
breathing isoflurane in a magnetic resonance (MR) scanner dedicated to small
animal MR. Here we describe the overall setup and steps for measuring 1H and 31P
MRS and 1H MRSI of orthotopic breast tumor models in mice with surface coils.
This protocol can be adapted to the use of volume coils to measure 1H and 31P
MRS(I) of tumor models that grow inside the body. We address issues of animal
handling, setting up the measurement, measurement options, and data analysis.
PMID- 29341019
TI - MRI in the Study of Animal Models of Neurodegenerative Diseases.
AB - Magnetic Resonance Imaging (MRI) is an important tool to study various animal
models of degenerative diseases. This chapter describes routine protocols of T 1
, T 2-, and T 2*-weighted and diffusion-weighted MRI for rodent brain and spinal
cord. These protocols can be used to measure atrophy, axonal and myelin injury
and changes in white matter connectivity.
PMID- 29341020
TI - MRI in the Study of Animal Models of Stroke.
AB - Stroke consists of the loss of cerebral functions resulting from the interruption
of blood supply to a region of the brain, and represents the second cause of
death and the leading cause of major disability in adults in Europe. Stroke is a
very active field of research at preclinical and clinical levels, and Magnetic
Resonance Imaging (MRI) is one of the most powerful tools that scientist and
clinicians have for the study of the onset, evolution and consequences of this
devastating disease, as well as for the monitoring of the success of available
treatments, or for the development of novel therapeutic strategies.MRI can tackle
the study of stroke from different points of view, and at scales ranging from
subcellular to systems biology level. Magnetic resonance spectroscopy (MRS)
allows the noninvasive measurement of the levels of principal metabolites in the
brain, and how they change during the course of the disease, or in response to
therapy. Glutamate, in particular, is very important in the field of stroke.
Several anatomical MR techniques allow the characterization of the lesion
volumes, the formation of cytotoxic and vasogenic edema, changes in cerebral
blood flow and volume, structural changes in gray and white matter, the obtaining
of the vascular architecture and status, etc. At functional level, diverse
modalities of functional MRI (fMRI) allow the assessment of the alteration in the
function and organization of neuronal networks of the subject under study, as a
consequence of the disease or in response to treatment. Finally, emerging imaging
modalities that include temperature and pH mapping of the brain, imaging by
chemical exchange saturation transfer effect (CEST), all of them closely related
to tissue status, or the use of contrast agents for the targeting of tissue in
theranostic approaches or for cell tracking studies in cell-based therapies,
etc., are only a few examples of the power and versatility of MRI as a definitive
tool for the study of stroke.In this work we will set our focus on preclinical
imaging of stroke models, emphasizing the most commonly used imaging modalities
in a stroke-dedicated research laboratory. However, advanced techniques will be
briefly discussed, providing references to specialized literature for more
advanced readers. Thus, the aim of this chapter consist in the description of a
simple imaging protocol for the study of the most important and common aspects of
stroke in a research laboratory.
PMID- 29341021
TI - Assessment of Blood Brain Barrier Leakage with Gadolinium-Enhanced MRI.
AB - The integrity of the blood-brain barrier (BBB) can be noninvasively monitored by
magnetic resonance imaging (MRI). Conventional MR contrast agents (CAs)
containing gadolinium are used in association with MRI in routine clinical
practice to detect and quantify BBB leakage. Under normal circumstances CAs do
not cross the intact BBB. However due to their small size they extravasate from
the blood into the brain tissue even when the BBB is partially compromised. Here
we describe an MR method based on T1-weighted images taken prior to and after CA
injection. This MR method is useful for investigating BBB permeability in in vivo
mouse models and can be easily applied in a number of experimental disease
conditions including neuroinflammation disorders, or to assess (un)wanted drug
effects.
PMID- 29341022
TI - In Vivo Pharmacokinetics of Magnetic Nanoparticles.
AB - Over the past few years, many papers have been published on the nanomedical
applications of magnetic nanoparticles. However, most studies lack important
information about the in vivo behavior of these nanoparticles, which is a
critical aspect for their rational design. In this chapter we describe a simple
protocol for the in vivo characterization of the pharmacokinetics of magnetic
nanoparticles intravenously injected in mice, using basic MRI sequences.
PMID- 29341023
TI - Anesthesia and Monitoring of Animals During MRI Studies.
AB - The use of imaging represents a major impact on the refinement and the reduction
of in vivo studies in animal models, in particular for allowing longitudinal
monitoring of the onset and the progression of disease within the same animal,
and studying the biological effects of drug candidate and their therapeutic
effectiveness. But the use of imaging procedures can affect animal physiology,
and the need to anesthetize the animals for imaging entails potential health
risks. During anesthesia, there is an inevitable autonomic nervous system
depression which induces cardiovascular depression, respiratory depression, and
hypothermia. Also other procedures associated with imaging such as animal
preparation (e.g., fasting, premedication), blood sampling, and dosage/contrast
agent injections can also affect physiology and animal welfare. All these factors
are likely to have confounding effect on the outcome of the imaging studies and
pose important concerns regarding the animal's well-being, particularly when
imaging immune deprived animals or diseased animals. We will discuss these
challenges and considerations during imaging to maximize efficacious data while
promoting animal welfare.
PMID- 29341024
TI - Advanced Contrast Agents for Multimodal Biomedical Imaging Based on
Nanotechnology.
AB - Clinical imaging modalities have reached a prominent role in medical diagnosis
and patient management in the last decades. Different image methodologies as
Positron Emission Tomography, Single Photon Emission Tomography, X-Rays, or
Magnetic Resonance Imaging are in continuous evolution to satisfy the increasing
demands of current medical diagnosis. Progress in these methodologies has been
favored by the parallel development of increasingly more powerful contrast
agents. These are molecules that enhance the intrinsic contrast of the images in
the tissues where they accumulate, revealing noninvasively the presence of
characteristic molecular targets or differential physiopathological
microenvironments. The contrast agent field is currently moving to improve the
performance of these molecules by incorporating the advantages that modern
nanotechnology offers. These include, mainly, the possibilities to combine
imaging and therapeutic capabilities over the same theranostic platform or
improve the targeting efficiency in vivo by molecular engineering of the
nanostructures. In this review, we provide an introduction to multimodal imaging
methods in biomedicine, the sub-nanometric imaging agents previously used and the
development of advanced multimodal and theranostic imaging agents based in
nanotechnology. We conclude providing some illustrative examples from our own
laboratories, including recent progress in theranostic formulations of
magnetoliposomes containing omega-3 poly-unsaturated fatty acids to treat
inflammatory diseases, or the use of stealth liposomes engineered with a pH
sensitive nanovalve to release their cargo specifically in the acidic
extracellular pH microenvironment of tumors.
PMID- 29341025
TI - Multiple sclerosis: Prevalence and impact.
AB - This article provides new information about multiple sclerosis (MS) using the
2010/2011 Neurological Conditions Prevalence File, the 2011/2012 Survey of
Neurological Conditions in Institutions in Canada, and the 2011 Survey on Living
with Neurological Conditions in Canada. An estimated 93,500 Canadians living in
private households and 3,800 residents of long-term care institutions had been
diagnosed with MS. Prevalence estimates were 159 and 418 cases per 100,000
population for men and women, respectively; 2.6 women reported MS for every man
with the condition. Among the household population, MS was generally diagnosed
between the ages of 20 and 49 (82%). For the majority (68%), MS was their only
neurological condition. The impact of MS included pain that prevented activities,
impairments in mobility, cognition or sleep, and limitations in social
functioning. Almost two-thirds (64%) stated that MS affected their lives at least
moderately.
PMID- 29341026
TI - Trends and correlates of frequency of fruit and vegetable consumption, 2007 to
2014.
AB - BACKGROUND: Eating fruit and vegetables is recommended as part of a healthy diet.
This study describes trends in the frequency of fruit and vegetable consumption
in Canada, the contribution of fruit juice to these trends, and correlates of the
frequency of fruit and vegetable consumption. DATA AND METHODS: The data are from
the annual Canadian Community Health Survey for the 2007-to-2014 period and
pertain to the household population aged 12 or older. Weighted frequencies and
cross-tabulations were used to estimate the average frequency of fruit and
vegetable consumption by socio-demographic characteristics and body mass index,
age-standardized to the 2014 Canadian population. Multivariate logistic
regressions were used to examine correlates of frequency of fruit and vegetable
intake in 2014. RESULTS: In 2014, Canadians reported consuming fruit and
vegetables an average of 4.7 times a day, a slight, but significant, decrease
from 5.0 times a day in 2007. The decrease over time was no longer significant
when fruit juice was excluded (dropping to an average of 4.1 times a day in both
years). Canadians drank less juice in 2014 than in 2007, a decline that was
apparent across all age, sex and household income quintiles, all regions, and all
weight categories. In 2014, Canadians who reported consuming fruit and vegetables
5 or more times a day tended to be female, in younger age groups, in the highest
household income quintile, and neither overweight nor obese. DISCUSSION: Between
2007 and 2014, Canadians' reported frequency of fruit and vegetable consumption
was consistently low. Correlates of fruit and vegetable consumption can be used
to target nutrition policy and education efforts to improve intake.
PMID- 29341027
TI - Developing Deep Learning Applications for Life Science and Pharma Industry.
AB - Deep Learning has boosted artificial intelligence over the past 5 years and is
seen now as one of the major technological innovation areas, predicted to replace
lots of repetitive, but complex tasks of human labor within the next decade. It
is also expected to be 'game changing' for research activities in pharma and life
sciences, where large sets of similar yet complex data samples are systematically
analyzed. Deep learning is currently conquering formerly expert domains
especially in areas requiring perception, previously not amenable to standard
machine learning. A typical example is the automated analysis of images which are
typically produced en-masse in many domains, e. g., in high-content screening or
digital pathology. Deep learning enables to create competitive applications in so
far defined core domains of 'human intelligence'. Applications of artificial
intelligence have been enabled in recent years by (i) the massive availability of
data samples, collected in pharma driven drug programs (='big data') as well as
(ii) deep learning algorithmic advancements and (iii) increase in compute power.
Such applications are based on software frameworks with specific strengths and
weaknesses. Here, we introduce typical applications and underlying frameworks for
deep learning with a set of practical criteria for developing production ready
solutions in life science and pharma research. Based on our own experience in
successfully developing deep learning applications we provide suggestions and a
baseline for selecting the most suited frameworks for a future-proof and cost
effective development.
PMID- 29341028
TI - Ameliorative Effects of Zataria Multiflora Hydro-Alcoholic extract on Gentamicin
Induced Nephrotoxicity in Rats.
AB - BACKGROUND: Nephrotoxicity is the major side effects of aminoglycoside
antibiotics such as gentamicin. The aim of this study was to investigate the
therapeutic effects of Z.multiflora (ZM) hydroalcoholic extract on gentamicin
induced nephrotoxicity. METHODS: Twenty-eight male Wistar rats categorized into
four groups: 1) the control group without injection, 2) the gentamicin treated
group (100 mg/kg, i.p) 3) the gentamicin and Z. Multiflora treated group; Z.
Multiflora extract(0.8 mg/ml in the drinking water) administered after gentamicin
(100 mg/kg, i.p) 4) the normal saline and Z. Multiflora treated group; Z.
Multiflora extract (0.8 mg/ml in the drinking water) administered after normal
saline injection (2 ml/kg,i.p ). RESULTS: Post-treatment with ZM extract caused a
significant reduction in the levels of plasma creatinine and blood urea nitrogen
(BUN), absolute and fractional excretion of sodium, malondialdehyed (MDA) level
in comparison to gentamicin group. In addition, ZM extract significantly
increased creatinine clearance, urine osmolarity, and Renal blood flow (RBF) and
the Ferric reducing ability of plasma (FRAP) level which had decreased compared
to the control group as a result of treatment with gentamicin. CONCLUSION: The
above result indicated that ZM extract improved renal toxicity of gentamicin via
reducing oxidative stress, oxygen-free radicals, and lipid peroxidation.
PMID- 29341029
TI - In Vitro and In Situ Absorption and Metabolism of Sesquiterpenes from Petasites
hybridus Extracts.
AB - Petasites hybridus extract is used in the treatment of seasonal allergic
rhinitis. The aim of this study was to evaluate the active constituent petasin
and its isomers isopetasin and neopetasin (petasins) in the P. hybridus extract
Ze 339 for liberation, dissolution, absorption, and metabolism. The determination
of pH-dependent thermodynamic solubility was performed via the shake-flask
method. Petasins exhibited a low solubility that was pH independent. In vivo, the
concentration of solute drugs is decreased continuously by intestinal absorption.
Therefore, low solubility is not assumed to be critical for in vivo performance.
Additionally, dissolution of an herbal medicinal product containing P. hybridus
extract Ze 339 was assessed. Furthermore, high permeability through Caco-2
monolayers was evident. Using an in situ rat model, absorption capacity for
petasins was found in all tested intestinal segments, namely, duodenum, jejunum,
and ileum. Besides, high metabolism was evident both in Caco-2 monolayers and in
the rat intestine. To compare intestinal and hepatic metabolism of petasins, in
vitro enzyme assays using liver and intestinal cytosol and microsomes (S9
fraction) of rats and humans were performed. A significantly higher metabolic
rate was found in the liver S9 fraction of both species compared with the
intestinal S9 fraction.
PMID- 29341030
TI - New Tirucallane-Type Triterpenoids from Guarea guidonia.
AB - The aerial parts of Guarea guidonia afforded three new tirucallane-type
triterpenoids: 3,4-seco-tirucalla-4(28),8(9),24(25)-trien-7alpha,11alpha
dihydroxy-21,23-epoxy-3,11-olide, named guareolide (1: ), 3,4-seco-tirucalla
4(28),7(8),24(25)-trien-21-hydroxy-21,23-epoxy-3-oic acid, named guareoic acid A
(2: ), and 3,4-seco-tirucalla-4(28),7(8),24(25)-trien-21,23-epoxy-3-oic acid,
named guareoic acid B (3: ), of which 1: possessed an unusual seven-membered
lactone ring. Seven known terpenes were also isolated and characterized as
flindissone, 7-acetyldihydronomilin, picroquassin E, boscartol C, and cneorubins
A, B, and X. Their structures were determined by spectroscopic methods including
one-dimensional and two-dimensional nuclear magnetic resonance analysis and high
resolution mass spectrometry. The isolates were investigated for their potential
cytotoxic activity on Jurkat, HeLa, and MCF7 cancer cell lines. Flindissone and
compound 2: showed an antiproliferative activity in all cell lines. Further
studies revealed that flindissone, the most active compound, induced in Jurkat
and HeLa cells both cytostatic and cytotoxic responses.
PMID- 29341031
TI - Getting More Than You Paid For: Unauthorized "Natural" Substances in Herbal Food
Supplements on EU Market.
AB - As the population in the industrialized world develops preference for what is
perceived as a natural and holistic way of disease treatment, the popularity and
the number of food supplements on the market, including herbal ones, is
experiencing an unprecedented rise. However, unlike herbal medicinal products,
intended for treating or preventing disease, current legislation classifies food
supplements as products intended for achieving nutritional or physiological
effect and to supplement the normal diet. Accordingly, most food supplements are
not to be associated with specific health claims. However, either due to the
subtle suggestions by the producers or the wishful thinking of the consumers,
certain pharmacological effects from food supplements are often expected.
Medicinal plants included in food supplements usually do not produce dramatic and
instant pharmacological effects. Therefore, in order to meet the expectation of
their customers, some producers have turned to the illicit and dangerous practice
of adulterating their products with synthetic adulterants, including naturally
occurring molecules, having the desired activity. Such practice is prevalent in,
although not limited to, food supplements intended for use as weight-loss aids,
as well as for sport performance and libido enhancement. The review is focusing
on naturally occurring alkaloids, phenylethanolamines, and their semi-synthetic
derivatives in food supplements in the European Union as reported by the Rapid
Alert System for Food and Feed. Their desired and undesired pharmacological
effects, as well as the methods for their detection and quantification in food
supplements, will be reviewed.
PMID- 29341032
TI - [Epidemiology, Diagnosis and Treatment of Adult Patients with Nosocomial
Pneumonia - Update 2017 - S3 Guideline of the German Society for Anaesthesiology
and Intensive Care Medicine, the German Society for Infectious Diseases, the
German Society for Hygiene and Microbiology, the German Respiratory Society and
the Paul-Ehrlich-Society for Chemotherapy, the German Radiological Society and
the Society for Virology].
AB - Nosocomial pneumonia (HAP) is a frequent complication of hospital care. Most data
are available on ventilator-associated pneumonia. However, infections on general
wards are increasing. A central issue are infections with multidrug resistant
(MDR) pathogens which are difficult to treat in the empirical setting potentially
leading to inappropriate use of antimicrobial therapy.This guideline update was
compiled by an interdisciplinary group on the basis of a systematic literature
review. Recommendations are made according to GRADE giving guidance for the
diagnosis and treatment of HAP on the basis of quality of evidence and
benefit/risk ratio.This guideline has two parts. First an update on epidemiology,
spectrum of pathogens and antimicrobials is provided. In the second part
recommendations for the management of diagnosis and treatment are given. New
recommendations with respect to imaging, diagnosis of nosocomial viral pneumonia
and prolonged infusion of antibacterial drugs have been added. The statements to
risk factors for infections with MDR pathogens and recommendations for
monotherapy vs combination therapy have been actualised. The importance of
structured deescalation concepts and limitation of treatment duration is
emphasized.
PMID- 29341033
TI - [Lung Volume Reduction Surgery].
AB - Lung volume reduction surgery (LVRS) offers improvement in lung function, quality
of life and even survival in well selected patients with severe emphysema.
Patients with all types of emphysema morphology can profit from LVRS when certain
selection criteria are present. Hyperinflation plays a key role in qualifying for
the procedure. Candidate selection should be performed at high volume centers
with a multidisciplinary emphysema board. Qualified thoracic surgeons together
with pulmonologists and radiologists identify the suitable patient considering
emphysema morphology with its target areas for resection, lung function
parameters and cardiac comorbidities. This review outlines candidate selection,
technique and results of LVRS to inform referring physicians how to screen und
inform their patients.
PMID- 29341034
TI - Therapeutic Assessment of Vulvar Squamous Intraepithelial Lesions with CO2 Laser
Vaporization in Immunosuppressed Patients.
AB - OBJECTIVE: A vulvar squamous intraepithelial lesion is deemed to be a preceding
lesion to vulvar cancer, especially in women aged under 40 years, holders of an
acquired or idiopathic immunosuppression. Several treatments have been used to
treat these lesions. One of the aesthetically acceptable therapeutic methods is
the CO2 laser vaporization. METHODS: In a transversal study, 46 records of
immunosuppressed women bearing a vulvar low grade and/or high grade squamous
intraepithelial lesion were selected out of the retrospective analysis, computing
age, date of record, date of vulvar lesion treatment with CO2 laser, the time
elapsed between the first and the last visit (in months), the number of visits,
the presence or absence of condylomatous lesions in other female lower genital
tract sites and whether or not recurrences and persistence of intraepithelial
lesions have been noticed during the follow-up. RESULTS: Patients bearing vulvar
high-grade squamous intraepithelial lesion and immunosuppressed (serum positive
for human immunodeficiency virus [HIV] or with solid organs transplantation) have
shown a higher level of persistence of lesions and a higher chance of having
other areas of the female lower genital tract involved. CONCLUSION: While the
CO2 laser vaporization is the most conservative method for the treatment of
vulvar high-grade intraepithelial lesions, it is far from being the ideal method,
due to the intrinsic infection features considered. The possibility of
persistence, recurrences and spontaneous limited regression indicates that a
closer surveillance in the long-term treated cases should be considered, in
special for immunosuppressed patients.
PMID- 29341035
TI - When an Unexpected Diagnosis Occurs: a Vaginal Premenopausal Sarcoma.
AB - Vaginal cancer is a rare entity. The evidence on its management resides mostly in
clinical cases or small case series. Of the histological types, the most frequent
is the squamous cell carcinoma, followed by adenocarcinoma. But what to do when
identifying an even more infrequent sarcoma in a premenopausal woman? In this
study, we describe the case of a 53-year-old woman presenting with metrorrhagia
for two months, who was evaluated after an intense episode. A necrotic and
ulcerative vaginal swelling was documented and then submitted to biopsy, which
revealed a vaginal sarcoma. The patient was referred to radiation therapy with 50
Gy (aiming to control the symptoms and to cause tumor reduction for posterior
pelvic exenteration with intraoperative radiotherapy) and developed an extra
pelvic metastization at the end of the treatment, which caused a fast negative
outcome. Despite the initial poor prognosis, a chemo-irradiation or primary
surgery regimen might have achieved (although with greater side effects) a better
survival. This case-report entails a discussion about the strategies to manage
vaginal sarcoma in advanced stage and in premenopausal women.
PMID- 29341036
TI - Zika Virus Infection, Pregnancy and Microcephaly.
PMID- 29341037
TI - Reply to: Zika Virus Infection, Pregnancy and Microcephaly.
PMID- 29341038
TI - [The use of Deep Inferior Epigastric Vessels to Revascularise Free Flaps for
Reconstruction of Complex Oncosurgical Defects of the Thigh and the Abdomen].
AB - BACKGROUND: The resection of large soft-tissue sarcoma requires reconstruction
with free flaps. The choice of recipient vessels is crucial for the success of
surgery. PATIENTS: We report four cases with large soft-tissue sarcomas with
complex anatomical relationships: two tumors of the thigh surrounding the femoral
neurovascular structures and two tumors of the abdomen with infiltration of the
thorax and the abdomen. All cases received multimodal interdisciplinary
treatment. The anterolateral thigh (ALT) flap and the latissimus dorsi (LD) flap
were employed twice for defect coverage in this series. In all cases the deep
inferior epigastric (DIE) vessels were transposed to the subcutaneous compartment
and used as recipient vessels. RESULTS: The mean duration of surgery was 694 +/-
149 minutes. The mean weight of the tumor specimen was 3069 +/- 1267 g. Three
flaps healed primarily and one exhibited a minor necrosis, which was treated by
excision and secondary suture. There were no cases of abdominal herniation due to
the transposition of vessels. CONCLUSION: Transposition of DIE-vessels to the
subcutaneus compartment is a good alternative for free flap revascularisation in
this patient group. In this position, the vessels are easily accessed and used
for microsurgery. This technical modification increases the reconstructive
possibilities in large and previously irradiated surgical defects.
PMID- 29341039
TI - Covert hepatic encephalopathy leads to distinct alterations in the emotional
state, independently of MELD-Score.
AB - BACKGROUND AND AIMS: Covert hepatic encephalopathy impairs many aspects of
quality of life, although its impact on the emotional state has not been
evaluated. This study aims to evaluate the impact of covert hepatic
encephalopathy on the emotional state and which factors are associated with
changes in the emotional state in patients with cirrhosis. METHODS: This single
center study included all patients with cirrhosis who underwent the portosystemic
encephalopathy syndrome (PSE) test, critical flicker frequency, and emotional
state assessment with the Eigenschaftsworterliste 60-S in 2011. Covert hepatic
encephalopathy was defined by abnormal PSE. Parametric and non-parametric tests
were used according to variable distribution. RESULTS: One hundred seventeen
patients with cirrhosis were included (median age: 59 [interquartile range: 48 -
67], 32 % female, 74 % alcohol-associated). Seventy patients had covert hepatic
encephalopathy (60 %) with a higher MELD (16 [interquartile range: 13 - 21], p =
0.001) and a higher Child-Pugh score (p = 0.003) compared to patients without
encephalopathy. Patients with covert encephalopathy felt reduced mental activity
(p = 0.004), lower general well-being (p = 0.001), and reduced extraversion (p =
0.021). The scores in the negative domains such as general lethargy (p = 0.031)
and anxiousness/depressiveness (p = 0.033) were higher in patients with covert
hepatic encephalopathy. There was no correlation between MELD and the emotional
state. Patients with 2 pathological tests (critical flicker frequency and PSE)
showed the most distinct alterations in the emotional state in the group of
patients with covert hepatic encephalopathy. CONCLUSIONS: Patients with covert
hepatic encephalopathy have an alteration of the emotional state, which is more
marked in patients with 2 pathological tests. Interestingly, MELD had no impact
on the emotional state.
PMID- 29341040
TI - Risk factors for allograft failure in liver transplant recipients.
AB - BACKGROUND: With regard to quality of life and organ shortage, follow-up after
liver transplantation (LT) should consider risk factors for allograft failure in
order to avoid the need for re-LT and to improve the long-term outcome of
recipients. Therefore, the aim of this study was to explore potential risk
factors for allograft failure after LT. MATERIAL AND METHODS: A total of 489
consecutive LT recipients who received follow-up care at the University Hospital
of Muenster were included in this study. Database research was performed, and
patient data were retrospectively reviewed. Risk factors related to donor and
recipient characteristics potentially leading to allograft failure were
statistically investigated using binary logistic regression analysis. Graft
failure was determined as graft cirrhosis, need for re-LT because of graft
dysfunction, and/or allograft-associated death. RESULTS: The mean age of
recipients at the time of LT was 50.3 +/- 12.4 years, and 64.0 % were male. The
mean age of donors was 48.7 +/- 15.5 years. Multivariable statistical analysis
revealed male recipient gender (p = 0.04), hepatitis C virus infection (HCV) (p =
0.014), hepatocellular carcinoma (HCC) (p = 0.03), biliary complications after LT
(p < 0.001), pretransplant diabetes mellitus (p = 0.03), and/or marked fibrosis
in the initial protocol biopsy during follow-up (p = 0.001) to be recipient
related significant and independent risk factors for allograft failure following
LT. CONCLUSION: Male recipients, patients who received LT for HCV or HCC, those
with pretransplant diabetes mellitus, and LT recipients with biliary
complications are at high risk for allograft failure and thus should be monitored
closely.
PMID- 29341041
TI - Screening interval recommendations following a normal colonoscopy in individuals
with a familial risk of colorectal cancer.
AB - BACKGROUND: In view of the increased risk of developing colorectal cancer (CRC)
in individuals with affected first-degree relatives (FDRs), the German evidence
based S3 guideline recommends having the first screening colonoscopy early and
then, following a normal examination, repeating it at least every 10 years. The
aim of this analysis was to explore colonoscopy interval recommendations in
clinical practice among individuals aged < 55 years with a familial risk of CRC.
METHODS: We analyzed data from the FRIDA.Frankfurt study. Patients aged 40 - 54
years with at least 1 reported FDR with CRC (excluding suspected/known hereditary
cancer syndromes) and a normal colonoscopy result (no findings) were included.
Data on colonoscopist recommendations for intervals between subsequent
colonoscopies were extracted from colonoscopy reports. RESULTS: Of 63 reports of
normal colonoscopies, 20 (32 %) did not include a recommendation on when to
undergo a further colonoscopy. Of 43 reports with recommendations, 40 (93 %)
suggested an interval that was shorter than the recommended maximum interval in
the guideline: 1 (2 %) was for a 3-year interval, 37 (86 %) were for 5-year
intervals, and 2 (5 %) were for 8-year intervals. CONCLUSIONS: Although the low
number of cases limits generalizability, the results indicate that recommended
intervals in clinical practice are considerably shorter than the recommended
maximum interval in the guideline.
PMID- 29341042
TI - [Prescription and risks of proton pump inhibitor: fiction and facts].
AB - There is substantial discussion about inappropriate prescriptions and risks of
proton pump inhibitor (PPI) therapy. This review critically reviews prescription
manners regarding PPI both by general practitioners and in hospitals,
demonstrates exit strategies after prolonged PPI treatment and evaluates
clinically relevant risks of PPI therapy.
PMID- 29341043
TI - Can Neonatal Brain MRI be Performed during Active Cooling?
AB - OBJECTIVE: Due to logistical constraints, physicians traditionally delay
diagnostic imaging for neonatal hypoxic-ischemic encephalopathy (HIE) until the
neonate has completed all 72 hours of therapeutic hypothermia and rewarming. In
some cases, neonates may require neuroimaging before 72 hours has passed. STUDY
DESIGN: We present a case in which an MRI was acquired during active
hypothermia. RESULTS: Upon return to the NICU, Baby X's temperature probe read
33.6 degrees, indicating that hypothermia was likely maintained at the target
temperature. CONCLUSION: Active hypothermia is possible during MRI.
PMID- 29341044
TI - Antenatal Medical Therapies to Improve Lung Development in Congenital
Diaphragmatic Hernia.
AB - Congenital diaphragmatic hernia (CDH) is a birth defect characterized by failed
closure of the diaphragm, allowing abdominal viscera to herniate into the
thoracic cavity and subsequently impair pulmonary and vascular development.
Despite improving standardized postnatal management, there remains a population
of severe CDH for whom postnatal care falls short. In these severe cases,
antenatal surgical intervention (fetoscopic endoluminal tracheal occlusion
[FETO]) may improve survival; however, FETO increases the risk of preterm
delivery, is not widely offered, and still fails in half of cases. Antenatal
medical therapies that stimulate antenatal pulmonary development are therefore
interesting alternatives. By presenting the animal research underpinning novel
antenatal medical therapies for CDH, and considering the applications of these
therapies to clinical practice, this review will explore the future of antenatal
CDH management with a focus on the phosphodiesterase-5 inhibitor sildenafil.
PMID- 29341045
TI - Approach to Infants Born Through Meconium Stained Amniotic Fluid: Evolution Based
on Evidence?
AB - Meconium-stained amniotic fluid (MSAF) during delivery is a marker of fetal
stress. Neonates born through MSAF often need resuscitation and are at risk of
meconium aspiration syndrome (MAS), air leaks, hypoxic-ischemic encephalopathy,
extracorporeal membrane oxygenation (ECMO), and death. The neonatal resuscitation
approach to MSAF has evolved over the last three decades. Previously, nonvigorous
neonates soon after delivery were suctioned under the vocal cords with direct
visualization technique using a meconium aspirator. The recent neonatal
resuscitation program (NRP) recommends against suctioning but favors
resuscitation with positive pressure ventilation of nonvigorous neonates with
MSAF. This recommendation is aimed to prevent delay in resuscitation and minimize
hypoxia-ischemia often associated with MSAF. In this review, we discuss the
pathophysiology, evolution and the evidence, randomized control trials,
observational studies, and translational research to support these
recommendations. The frequency of ECMO use for neonatal respiratory indication of
MAS has declined over the years probably secondary to improvements in neonatal
intensive care and reduction of postmaturity. Changes in resuscitation practices
may have contributed to reduced incidence and severity of MAS. Larger randomized
controlled studies are needed among nonvigorous infants with MSAF. However,
ethical dilemmas and loss of equipoise pose a challenge to conduct such studies.
PMID- 29341046
TI - Reduced Growth Hormone Secretion is Associated with Nonalcoholic Fatty Liver
Disease in Obese Children.
AB - The purpose of the study was to evaluate the relationship between arginine
levodopa-induced growth hormone (GH) secretion and nonalcoholic fatty liver
disease (NAFLD) in obese children. This study includes a total of 84 obese and 43
normal weight children. The obese subjects are divided into two groups based on
the presence or absence of NAFLD. Clinical examination, anthropometric and
laboratory examinations, and liver ultrasonography are assessed for all
participants. The obese group had significantly lower peak stimulated GH
(p<0.001) and lower insulin-like growth factor 1 (IGF-1) (p<0.001) compared with
the control group. Children with NAFLD had significantly lower peak stimulated GH
(p<0.001) and lower IGF-1 (p=0.022) compared with non-NAFLD group. Results from
logistic regression model showed that only peak GH after stimulation test was
inversely associated with NAFLD (p=0.015), while body mass index (BMI) was
positively associated with NAFLD (p=0.03). Among 84 obese children and
adolescents, peak stimulated GH was negatively associated with alanine
aminotransferase (r=-0.394, p<0.001), BMI (r=-0.571, p<0.001), systolic blood
pressure (r=-0.223, p=0.041), diastolic blood pressure (r=-0.272, p=0.012),
homeostasis model assessment of insulin resistance (r=-0.369, p=0.001), insulin
(r=-0.382, p<0.001), and positively associated with high density lipoprotein
cholesterol (r=0.275, p=0.011). Our study confirms a significant inverse
relationship between NAFLD and GH response to standard stimulation testing in
obese children without known hypothalamic/pituitary disease.
PMID- 29341047
TI - German Guideline for Idiopathic Pulmonary Fibrosis - Update on Pharmacological
Therapies 2017.
AB - Idiopathic pulmonary fibrosis (IPF) is a severe and often fatal disease with a
median survival of 2 - 4 years after diagnosis. Since the publication of the
German IPF guideline in 2013 new treatment trials have been published,
necessitating an update of the pharmacological therapy of IPF. Different from the
previous guideline, the GRADE system was discarded and replaced by the Oxford
evidence classification system which allows a more differentiated judgement. The
following pharmacological therapies were rated not suitable for the treatment of
IPF patients (recommendation A; evidence 1-b): triple therapy with prednisolone,
azathioprine and acetyl-cysteine; imatinib; ambrisentan; bosentan; macitentan. A
less clear but still negative recommendation (B, 1-b) was attributed to the
treatment of IPF with the phosphodiesterase-5-inhibitor sildenafil and acetyl
cysteine monotherapy. In contrast to the international guideline antacid therapy
as a general treatment for IPF was rated negative, based on conflicting results
of recent analyses (recommendation C; evidence 4). An unanimous positive
recommendation was granted for the antifibrotic drugs nintedanib and pirfenidone
for the treatment of IPF (A, 1-a). For some open questions in the management of
IPF patients for which firm evidence is lacking the guideline also offers
recommendations based on expert consensus.
PMID- 29341048
TI - Intrapartum Care Working Patterns of Midwives: The Long Road to Models of Care in
Germany.
AB - INTRODUCTION: Midwifery models of care help to enhance perinatal health outcomes,
women's satisfaction, and continuity of care. Despite the ubiquitous presence of
certified midwives at births in Germany, no research has investigated the
diversity of midwives' practice patterns. Describing the variety of working
patterns through which midwives provide intrapartum care may contribute to
improving the organisation of midwifery services. METHODS: This cross-sectional
survey took place in the region of Hannover and Hildesheim, Germany. Midwives
attending births and practicing in hospitals and/or out-of-hospital were able to
participate. Midwives who did not attend births were excluded. We assessed
midwives' scope of services, practice locations, employment patterns, continuity
of care, midwife-led births, and midwives' level of agreement with core values of
midwifery care. The response rate of the survey was 32.7 % (69/211). RESULTS: We
found that midwifery care services can be described according to midwives'
employment patterns. The majority of midwives were employed in a hospital to
provide intrapartum care (74.2 %, n = 49), and most also independently offered
one or more antenatal and/or postpartum service/s. Only 25.8 % (n = 17) of
midwives offered their services independently (laborist model of care).
Independent midwives attended births in all three possible settings: hospital,
free-standing birth centres and home. Significantly more independent midwives
than employed midwives offered antenatal care and lactation consulting. Compared
to employed midwives, significantly more independent midwives provided antenatal,
intrapartum, and postpartum care to the same women, were more likely to know
women before labour, and to offer one-to-one care during labour. DISCUSSION: The
most common practice pattern among surveyed midwives was 'employment in a
hospital' for provision of intrapartum care with additional postpartum and few
antenatal services provided on an independent basis. Midwives who worked solely
independently reported more continuity and one-to-one intrapartum care with
women. Most midwives did not work in patterns that offered continuity of care or
consistently provide one-to-one care. Future research should assess whether women
in Germany desire more services similar to caseload midwifery.
PMID- 29341049
TI - [Long-term Outcome after Prenatal Drug Exposure].
AB - Although prenatal exposure to opioids, cannabinoids and cocaine is a frequent
problem, only scarce data have been published on the long-term outcome in
affected children and adolescents. While opioid-exposed children up to the age of
2 years show a reduced motor developmental pattern, data from meta-analyses up to
adolescence show a strong trend for reduced performance with regard to cognitive
function and behavior. Follow-up data after intrauterine cannabinoid exposure
indicate reduced cognitive and reading abilities as well as abnormal findings in
complex planning tests. Externalizing pathologies have been observed more
frequently in boys. Prenatal cocaine exposure results in reduced cognitive and
verbal development up to adolescence; however, differences are small but
significant in meta-analyses. Interpretation of follow-up data with partially
contradictory results may reflect methodological differences and a number of
modifying co-factors, e.g., social conditions during the childhood period. These
data should encourage further primary and secondary preventive attempts.
PMID- 29341050
TI - [Reading is good for you!]
PMID- 29341051
TI - [The Journal in 2017].
PMID- 29341052
TI - [Routine outcome monitoring in anxiety disorders: diagnosis-specific versus
generic assessment instruments].
AB - BACKGROUND: Mental health institutions increasingly utilise routine outcome
monitoring (rom) in order to assess treatment effectiveness. It remains unclear
which instruments are more sensitive to change with regard to rom in patients
with an anxiety disorder: diagnosis-specific or generic instruments.
AIM: To
compare the sensitivity of diagnosis-specific versus generic rom-instruments in
patients with an anxiety disorder.
METHOD: 160 adults with an anxiety
disorder received cognitive behavioural therapy at the Altrecht Academic Anxiety
Centre. Approximately half of the population also received medication. Patients
completed an assessment both before and after treatment. This consisted of two
generic instruments (Outcome Questionnaire (oq-45) and Brief Symptom Inventory
(bsi)) and two diagnosis-specific instruments, determined by the main
diagnosis.
RESULTS: The differences between pre- and post-treatment
assessments were generally larger for the generic bsi and diagnosis-specific
instruments than for the generic oq-45.
CONCLUSION: When assessed after
cognitive behavioural therapy, the (generic) bsi and diagnosis-specific
instruments indicated larger progress than the oq-45. The bsi might be a
relatively diagnosis-specific measure for anxiety disorders. when selecting an
instrument for assessment, both the intended goal of treatment (symptom reduction
or improvement in quality of life) and other reasons for assessment should be
taken into consideration. The bsi or diagnosis-specific instruments are preferred
if the goal is to assess the change in specific anxiety symptoms.
PMID- 29341053
TI - [The use of anticonvulsants and the levels of folate, vitamin B12 and
homocysteine].
AB - BACKGROUND Patients with epilepsy who use anticonvulsants frequently show low
levels of folate and vitamin B12 and high levels of homocysteine. Patients with
bipolar disorder use some anticonvulsants as mood stabilisers.
AIM: To
determine whether some anticonvulsants lower folate and vitamin B12 and raise
homocysteine levels.
METHOD: Systematic literature search to determine the
relation between the anticonvulsants valproic acid, carbamazepine, lamotrigine
and topiramate on the one hand and blood levels of folate, vitamin B12 and
homocysteine on the other hand.
RESULTS: The vast majority of studies in
adults and children showed a correlation between use of anticonvulsant
carbamazepine and decrease of the folate level. Hardly any of the studies that
examined the effect of valproic acid on folate levels found a correlation. There
was next to no evidence of a correlation between the use of carbamazepine and a
low vitamin B12 level in adults or children. In adults and children the use of
valproic acid was found to correlate with a higher vitamin B12 level. Nearly all
studies found an increase in homocysteine in adults and children using
carbamazepine. Among the users of valproic acid, it was only children who showed
a clear association with a rise in homocysteine level. The results for adults
were contradictory. We were unable to make any clear statement about topiramate
or lamotrigine because there have been very few publications about these
anticonvulsants.
CONCLUSION: In adults and children with epilepsy use of
carbamazepine is associated with a decrease of folate, valproic acid with a rise
in the vitamin B12 level, and carbamazepine with an increase in homocysteine.
Valproic acid showed only in children an association with the rise of the
homocysteine level. Psychiatrists may find it advisable to control the levels of
folate and homocysteine in adults and children who are taking carbamazepine and
to measure homocysteine level in children taking valproic acid.
PMID- 29341054
TI - [A relational ethical model for the assessment of decision-making competence in
psychiatry].
AB - BACKGROUND: Nowadays, partly due to legislation, decision-making competence is
playing an ever-increasing role in psychiatry. So far, however, there are no
clear criteria for evaluating the actual competence of the procedure.
AIM:
To develop a relational ethical model, including criteria and methodology, which
can be used to assess and enhance decision-making competence mainly from a
relational and ethical perspective.
METHOD: Combination of a review of the
literature and ethical reflection. First of all, a limited study was made of the
literature relating to the concept of and criteria for decision-making
competence. On the basis of the literature and relational ethical reflection, ten
criteria were developed for decision-making competence and a method was devised
for assessing the procedure.
RESULTS: The criteria that have to be satisfied
can be summarised as follows: the persons involved must understand the
information, and must be able to apply it to their own situation. They must be
able to gain insight into their own situation and be able to weigh up the
available options, and be able to estimate consequences for themselves, as well
as for others. They must be able to motivate choices in a sensible and
comprehensible manner without being subject to coercive influences coming from
internal and external sources. Participants' choices should be motivated on the
basis of their own personal values. The decision-making competence is assessed
and enhanced by giving a score to the individual criteria and by making an
overall evaluation. This is achieved by a dialogue including all the persons
involved: the care seeker (as far as possible), close relatives and the care
providers.
CONCLUSION: The persons involved can attain greater objectivity
by exchanging views orally on the ten proposed criteria for decision-making
competence.
PMID- 29341055
TI - [Hallucinations and art].
AB - BACKGROUND Hallucinations and art appear to be inextricably connected, and yet
the question remains in how far artists make use of hallucinations for their work
in daily practice.
AIM: To chart the ways in which the fine arts are
influenced by hallucinations, an explorative literature search was carried out.
METHOD The search was carried out in PubMed, Google, and the historical
literature.
RESULTS: Some famous examples of artists who drew on
hallucinations for their work, are Hildegard of Bingen, William Blake, and Yayoi
Kusama. Especially among the surrealists, we also find indications of the use of
pareidolias, metamorphopsias, and other positive disorders of visual
perception.
CONCLUSION: In the art literature, the term hallucination is
often used in a broader sense than in medicine. As a consequence, the suggestion
that hallucinations would be lying at the basis of many works of art cannot be
confirmed, even though some spectacular examples can certainly be pointed out.
PMID- 29341056
TI - [Researching crisis plans in long-term mental health care: more complicated than
expected].
AB - BACKGROUND Crisis plans are highly valued because they can help to reduce the
number of persons subjected to compulsory treatment in mental health care. The
evidence however that crisis plans are effective is scarce, partly due to
insufficient implementation by professionals.
AIM: To assess the fidelity,
relevance and applicability of crisis plans and to estimate to what extent such
plans are appreciated by those working in long-term care.
METHOD: Semi
structured interview with patients and nurses.
RESULTS: The crisis plans
were judged to be clearly worded and the fidelity was high, but our findings
cannot be considered as representative because the response rate (12/144; 8.3%)
of the patients was so low.
CONCLUSION: Despite the accessibility of our
study design, patient response rates were very low. This demonstrates that
clinical research in long-term clinical health care clinical research can prove
to be more complicated than we anticipated. If the research participation rate
among these very ill and vulnerable population is commonly so low, it will be
extremely difficult for us to provide evidence-based care for these patients.
PMID- 29341057
TI - [Suicidal adolescents can benefit from Family Group Conferences].
AB - A risk factor among suicidal adolescents is generally their inability to form and
maintain relationships with other people. In the case that we investigated, the
technique known as Family Group Conference (FGC) was used successfully to break
through the adolescent's passivity and social isolation. The FGC also helped to
alter the adolescent's conviction of being a burden to relatives, friends and
other people. The results are in line with additional studies that used FGC with
other target groups. This case study suggests that FGC is a promising type of
intervention that can reduce the passivity and isolation of suicidal adolescents,
strengthening their relationships and boosting a feeling of belonging. These
factors as well as the results of the case investigated are currently stimulating
further research into the use of FGCs to foster feelings of belonging and
togetherness among suicidal adolescents.
PMID- 29341058
TI - [Takotsubo cardiomyopathy and catatonia in a patient with psychotic depression].
AB - Takotsubo cardiomyopathy (tcmp) is an acute, reversible disruption of the left
ventricular systolic function. In many respects the clinical presentation closely
resembles acute coronary syndromes (myocardial infarction). tcmp is a syndrome
with a pathophysiology that is not fully understood and which seems to be closely
associated with psychiatric disorders or psychological problems. We present a
case in which a patient with several risk factors developed a tcmp and a
depression with psychotic features, followed by catatonia. We describe the
syndrome, make some pathophysiological hypotheses and point to possible
connections with psychiatric disorders and psychological factors.
PMID- 29341059
TI - Down-regulated REIC expression in lung carcinogenesis: a molecular target for
gene therapy.
AB - REIC (Reduced Expression in Immortalized Cells) gene is down-regulated in
immortalized cells, compared with the normal parental counterparts. Its encoding
protein could inhibit colony formation, tumor growth, and induce apoptosis. To
investigate the roles of REIC expression in lung cancer, we examined REIC
expression in lung cancer cells and tissues by RT-PCR or Western blot, and
observed the effects of both recombinant REIC exposure and REIC overexpression on
the aggressive phenotypes of lung cancer cells. It was found that the
demethylation of REIC promoter by 5-Aza-dC could reserve its mRNA expression in
lung cancer cells (P<0.05). There was a lower REIC mRNA expression in lung cancer
than that in matched normal tissue (P<0.05). Recombinant REIC treatment enhanced
the proliferation of lung cancer cells (P<0.05), but versa for REIC
overexpression (P<0.05). Both recombinant REIC treatment and REIC overexpression
induced apoptosis, and inhibited the migration and invasion of SQ-5 and KJ cells
(P<0.05). Immunohistochemically, there was a positive correlation between REIC
and Caspase-3 expression in lung cancer (P<0.05). According to Kaplan-Meier
plotter, REIC mRNA overexpression was found to positively correlate with overall,
progression-free and post- progression survival rates of lung cancer patients
(P<0.05), even stratified by sex, histological subtyping, grading, TNM staging,
chemotherapy, radiotherapy, or smoking. These findings suggested that the down
regulated REIC expression might be involved in lung carcinogenesis due to its
promoter methylation. Both recombinant REIC exposure and REIC overexpression
might reverse the aggressive phenotypes of lung cancer cells. REIC may be
employed as a potential target of gene therapy for lung cancer.
PMID- 29341060
TI - Rationale of decreasing low-density lipoprotein cholesterol below 70 mg/dL in
patients with coronary artery disease: A retrospective virtual histology.
Intravascular ultrasound study.
AB - BACKGROUND: The associations between statin and coronary plaque compositional
changes were reported according to the use of high dose or not. An evaluation of
the impact of low-density lipoprotein cholesterol (LDL-C) < 70 mg/dL by using
real world dosages of statin on coronary plaque composition was undertaken.
METHODS: The study subjects consisted of 61 patients (mean 59.9 years old, 45
males) who underwent percutaneous coronary intervention, baseline and follow-up
(F/U; mean 8.4 months) virtual histology-intravascular ultrasound (VH-IVUS)
examination. Change of plaque composition at peri-stent area, which was selected
in order to measure the identical site at F/U study, was compared according to
the F/U LDL-C level. RESULTS: Body mass index, prevalence of dyslipidemia,
baseline total cholesterol and baseline LDL-C were significantly lower in F/U LDL
C < 70 mg/dL group (14 segments in 10 patients) than F/U LDL-C ? 70 mg/dL group
(79 segments in 51 patients). F/U high-density lipoprotein cholesterol (HDL-C, OR
1.06, 95% CI 1.00-1.11, p = 0.054) and F/U LDL-C < 70 mg/dL (OR 3.43, 95% CI 0.97
12.17, p = 0.056) showed strong tendency of regression of necrotic core volume
(NCV) >= 10%. In multivariable logistic regression analysis, F/U HDL-C (OR 1.07,
95% CI 1.01-1.14, p = 0.020) and F/U LDL-C level < 70 mg/dL (OR 8.02, 95% CI 1.58
40.68, p = 0.012) were the independent factors for regression of NCV ? 10%.
CONCLUSIONS: F/U LDL-C level < 70 mg/dL with any types of statins and increase of
HDL-C were associated with regression of NCV ? 10% in patients with coronary
artery disease.
PMID- 29341061
TI - Pericardial effusion unrelated to surgery is a predictor of mortality in heart
transplant patients.
AB - BACKGROUND: Hemodynamically irrelevant pericardial effusion (PeEf) is a predictor
of adverse outcome in heart failure patients. The clinical relevance of a PeEf
unrelated to surgery in heart transplant patients remains unknown. This study
assesses the prognostic value of PeEf occurring later than one year after
transplantation. METHODS: All patients undergoing heart transplantation in Zurich
between 1989 and 2012 were screened. Cox proportional hazard models were used to
analyse mortality (primary) and hospitalization (secondary endpoint). PeEf time
points were compared to baseline for rejection, immunosuppressants, tumours,
inflammation, heart failure, kidney function, hemodynamic, and echocardiographic
parameters. RESULTS: Of 152 patients (mean age 48.3 +/- 11.9), 25 developed PeEf.
Median follow-up period was 11.9 (IQR 5.8-17) years. The number of deaths was 6
in the PeEf group and 46 in the non-PeEf group. The occurrence of PeEf was
associated with a 2.5-fold increased risk of death (HR 2.49, 95% CI 1.02-6.13, p
= 0.046) and hospitalization (HR 2.53, 95% CI 1.57-4.1, p = 0.0002). CONCLUSIONS:
This study reveals that the finding of hemodynamically irrelevant PeEf in heart
transplant patients is a predictor of adverse outcome, suggesting that a careful
clinical assessment is warranted in heart transplant patients exhibiting small
PeEf.
PMID- 29341062
TI - Reflectance confocal microscopy for the diagnosis of Langerhans cell
histiocytosis.
PMID- 29341063
TI - Localized inflammatory reactions at sites of subcutaneous methotrexate injections
during treatment with ultraviolet B.
PMID- 29341064
TI - Can Addressing Personality Change Enhance Cognitive Functioning and Delay
Development of Mild Cognitive Impairment?
PMID- 29341065
TI - The use of methotrexate in adolescents: contraception, confidentiality and
consent.
PMID- 29341066
TI - Cerebral near-infrared spectroscopy (NIRS) for perioperative monitoring of brain
oxygenation in children and adults.
AB - BACKGROUND: Various techniques have been employed for the early detection of
perioperative cerebral ischaemia and hypoxia. Cerebral near-infrared spectroscopy
(NIRS) is increasingly used in this clinical scenario to monitor brain
oxygenation. However, it is unknown whether perioperative cerebral NIRS
monitoring and the subsequent treatment strategies are of benefit to patients.
OBJECTIVES: To assess the effects of perioperative cerebral NIRS monitoring and
corresponding treatment strategies in adults and children, compared with blinded
or no cerebral oxygenation monitoring, or cerebral oxygenation monitoring based
on non-NIRS technologies, on the detection of cerebral oxygen desaturation events
(CDEs), neurological outcomes, non-neurological outcomes and socioeconomic impact
(including cost of hospitalization and length of hospital stay). SEARCH METHODS:
We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2016,
Issue 12), Embase (1974 to 20 December 2016) and MEDLINE (PubMed) (1975 to 20
December 2016). We also searched the World Health Organization (WHO)
International Clinical Trials Registry Platform for ongoing studies on 20
December 2016. We updated this search in November 2017, but these results have
not yet been incorporated in the review. We imposed no language restriction.
SELECTION CRITERIA: We included all relevant randomized controlled trials (RCTs)
dealing with the use of cerebral NIRS in the perioperative setting (during the
operation and within 72 hours after the operation), including the operating room,
the postanaesthesia care unit and the intensive care unit. DATA COLLECTION AND
ANALYSIS: Two authors independently selected studies, assessed risk of bias and
extracted data. For binary outcomes, we calculated the risk ratio (RR) and its
95% confidence interval (CI). For continuous data, we estimated the mean
difference (MD) between groups and its 95% CI. As we expected clinical and
methodological heterogeneity between studies, we employed a random-effects model
for analyses and we examined the data for heterogeneity (I2 statistic). We
created a 'Summary of findings' table using GRADEpro. MAIN RESULTS: We included
15 studies in the review, comprising a total of 1822 adult participants. There
are 12 studies awaiting classification, and eight ongoing studies.None of the 15
included studies considered the paediatric population. Four studies were
conducted in the abdominal and orthopaedic surgery setting (lumbar spine, or knee
and hip replacement), one study in the carotid endarterectomy setting, and the
remaining 10 studies in the aortic or cardiac surgery setting. The main sources
of bias in the included studies related to potential conflict of interest from
industry sponsorship, unclear blinding status or missing participant data.Two
studies with 312 participants considered postoperative neurological injury,
however no pooled effect estimate could be calculated due to discordant direction
of effect between studies (low-quality evidence). One study (N = 126) in
participants undergoing major abdominal surgery reported that 4/66 participants
experienced neurological injury with blinded monitoring versus 0/56 in the active
monitoring group. A second study (N = 195) in participants having coronary artery
bypass surgery reported that 1/96 participants experienced neurological injury in
the blinded monitoring group compared with 4/94 participants in the active
monitoring group.We are uncertain whether active cerebral NIRS monitoring has an
important effect on the risk of postoperative stroke because of the low number of
events and wide confidence interval (RR 0.25, 95% CI 0.03 to 2.20; 2 studies, 240
participants; low-quality evidence).We are uncertain whether active cerebral NIRS
monitoring has an important effect on postoperative delirium because of the wide
confidence interval (RR 0.63, 95% CI 0.27 to 1.45; 1 study, 190 participants; low
quality evidence).Two studies with 126 participants showed that active cerebral
NIRS monitoring may reduce the incidence of mild postoperative cognitive
dysfunction (POCD) as defined by the original studies at one week after surgery
(RR 0.53, 95% CI 0.30 to 0.95, I2 = 49%, low-quality evidence).Based on six
studies with 962 participants, there was moderate-quality evidence that active
cerebral oxygenation monitoring probably does not decrease the occurrence of POCD
(decline in cognitive function) at one week after surgery (RR 0.62, 95% CI 0.37
to 1.04, I2 = 80%). The different type of monitoring equipment in one study could
potentially be the cause of the heterogeneity.We are uncertain whether active
cerebral NIRS monitoring has an important effect on intraoperative mortality or
postoperative mortality because of the low number of events and wide confidence
interval (RR 0.63, 95% CI 0.08 to 5.03, I2= 0%; 3 studies, 390 participants; low
quality evidence). There was no evidence to determine whether routine use of NIRS
based cerebral oxygenation monitoring causes adverse effects. AUTHORS'
CONCLUSIONS: The effects of perioperative active cerebral NIRS monitoring of
brain oxygenation in adults for reducing the occurrence of short-term, mild POCD
are uncertain due to the low quality of the evidence. There is uncertainty as to
whether active cerebral NIRS monitoring has an important effect on postoperative
stroke, delirium or death because of the low number of events and wide confidence
intervals. The conclusions of this review may change when the eight ongoing
studies are published and the 12 studies awaiting assessment are classified. More
RCTs performed in the paediatric population and high-risk patients undergoing non
cardiac surgery (e.g. neurosurgery, carotid endarterectomy and other surgery) are
needed.
PMID- 29341067
TI - Vitamin E for antipsychotic-induced tardive dyskinesia.
AB - BACKGROUND: Antipsychotic (neuroleptic) medication is used extensively to treat
people with chronic mental illnesses. Its use, however, is associated with
adverse effects, including movement disorders such as tardive dyskinesia (TD) - a
problem often seen as repetitive involuntary movements around the mouth and face.
Vitamin E has been proposed as a treatment to prevent or decrease TD. OBJECTIVES:
The primary objective was to determine the clinical effects of vitamin E in
people with schizophrenia or other chronic mental illness who had developed
antipsychotic-induced TD.The secondary objectives were:1. to examine whether the
effect of vitamin E was maintained as duration of follow-up increased;2. to test
the hypothesis that the use of vitamin E is most effective for those with early
onset TD (less than five years) SEARCH METHODS: We searched the Cochrane
Schizophrenia Group Trials Register (July 2015 and April 2017), inspected
references of all identified studies for further trials and contacted authors of
trials for additional information. SELECTION CRITERIA: We included reports if
they were controlled trials dealing with people with antipsychotic-induced TD and
schizophrenia who remained on their antipsychotic medication and had been
randomly allocated to either vitamin E or to a placebo, no intervention, or any
other intervention. DATA COLLECTION AND ANALYSIS: We independently extracted data
from these trials and we estimated risk ratios (RR) or mean differences (MD),
with 95% confidence intervals (CI). We assumed that people who left early had no
improvement. We assessed risk of bias and created a 'Summary of findings' table
using GRADE. MAIN RESULTS: The review now includes 13 poorly reported randomised
trials (total 478 people), all participants were adults with chronic psychiatric
disorders, mostly schizophrenia, and antipsychotic-induced TD. There was no clear
difference between vitamin E and placebo for the outcome of TD: not improved to a
clinically important extent (6 RCTs, N = 264, RR 0.95, 95% CI 0.89 to 1.01, low
quality evidence). However, people allocated to placebo may show more
deterioration of their symptoms compared with those given vitamin E (5 RCTs, N =
85, RR 0.23, 95% CI 0.07 to 0.76, low-quality evidence). There was no evidence of
a difference in the incidence of any adverse effects (9 RCTs, N = 205, RR 1.21,
95% CI 0.35 to 4.15, very low-quality evidence), extrapyramidal adverse effects
(1 RCT, N = 104, MD 1.10, 95% CI -1.02 to 3.22, very low-quality evidence), or
acceptability of treatment (measured by participants leaving the study early)
(medium term, 8 RCTs, N = 232, RR 1.07, 95% CI 0.64 to 1.80, very low-quality
evidence). No trials reported on social confidence, social inclusion, social
networks, or personalised quality of life, outcomes designated important to
patients. There is no trial-based information regarding the effect of vitamin E
for those with early onset of TD. AUTHORS' CONCLUSIONS: Small trials of limited
quality suggest that vitamin E may protect against deterioration of TD. There is
no evidence that vitamin E improves symptoms of this problematic and disfiguring
condition once established. New and better trials are indicated in this under
researched area, and, of the many adjunctive treatments that have been given for
TD, vitamin E would be a good choice for further evaluation.
PMID- 29341068
TI - Analysis of hypo- and hypermagnesemia in an intensive care unit cohort.
AB - INTRODUCTION: The aim of this study was to evaluate if magnesium deviations
correlate with higher 180 day overall mortality or increased morbidity, compared
to controls. METHODS: We conducted a retrospective study on 5369 patients with
22,003 magnesium values treated at the Adult Intensive Care Unit at Skane
University Hospital, Lund, Sweden during 2006-2014. The patients were
retrospectively divided into a control group with only normal magnesium values
0.7-1.0 mmol/l, and three study groups; hypomagnesemic; Mg2+ < 0.7 mmol/l,
hypermagnesemic; Mg2+ > 1.0 mmol/l and an unstable mixed group showing both
hypo/hypermagnesemia. Gender, age, disease severity represented by maximum organ
system SOFA score, renal SOFA score, lowest potassium value and diagnoses classes
were included in a Cox hazard model in order to adjust for confounding factors,
with time to death in the first 180 days from the ICU admission as outcome.
RESULTS: The hypermagnesemic study group and the mixed group showed increased
hazard ratios for mortality; 1.4 (CI 98.3% 1.2, 1.6, P < 0.0001) and 2.1 (CI
98.3% 1.2, 2.8, P < 0.0001) respectively, compared to controls, while the
hypomagnesemic group did not reach significance. In addition, patients in the
hypermagnesemic and the mixed groups are older, more ill with significantly
higher EMR and SOFA scores and show significantly longer ventilator times and ICU
stays, compared to controls. CONCLUSIONS: Patients with magnesium deviations are
more ill compared to patients with explicitly normal magnesium values throughout
the ICU stay. Cox analysis suggests that the magnesium deviation itself might
have an impact on mortality.
PMID- 29341069
TI - Reliability and validity of the instrument for scoring clinical outcomes of
research for epidermolysis bullosa (iscorEB).
AB - BACKGROUND: Epidermolysis bullosa (EB) is a group of rare and currently incurable
genetic blistering disorders. As more pathogenic-driven therapies are being
developed, there is an important need for EB-specific validated outcomes measures
designed for use in clinical trials. OBJECTIVES: To test the reliability and
construct validity of an instrument for scoring clinical outcomes of research for
EB (iscorEB), a new combined clinician- and patient-reported outcomes tool.
METHODS: We conducted an observational study consisting of independent 1-day
assessments (six assessors) at two academic hospitals. The assessments consisted
of iscorEB clinician (iscorEB-c), Birmingham Epidermolysis Bullosa Severity
(BEBS) and global severity assessment for physicians; and iscorEB patient
(iscorEB-p), Quality of Life evaluation in Epidermolysis Bullosa and Children's
Dermatology Life Quality Index for patients. Construct validity and intraclass
correlation coefficients (ICCs) for interobserver, intraobserver and test-retest
reliability were calculated. RESULTS: Overall, 31 patients with a mean age of
19.5 years (1.8-45.2) were included. Disease severity was mild in 42% of cases,
moderate in 29% and severe in 29%. The interobserver ICC was 0.96 for both the
clinician-reported section of iscorEB-c and BEBS. The ICC for intraobserver
reliability was 0.91 and 0.70 for the skin and mucosal domains of iscorEB-c,
respectively. Cronbach's alpha for iscorEB-c was 0.89. The test-retest
reliability of iscorEB-p was 0.97 and Cronbach's alpha was 0.84. The clinical
score differentiated between subjects with mild, moderate and severe disease, and
both clinical and patient subscores discriminated between recessive dystrophic EB
and other EB subtypes. CONCLUSIONS: iscorEB has robust reliability and construct
validity, including strong ability to distinguish EB types and severities.
Further studies are planned to test its responsiveness to change.
PMID- 29341072
TI - Epidermal melanocytes in segmental vitiligo show altered expression of E
cadherin, but not P-cadherin.
PMID- 29341070
TI - Personality Changes During the Transition from Cognitive Health to Mild Cognitive
Impairment.
AB - BACKGROUND/OBJECTIVES: Behavioral problems in individuals with Alzheimer's
disease (AD) impose major management challenges. Current prevention strategies
are anchored to cognitive outcomes, but behavioral outcomes may provide another,
clinically relevant opportunity for preemptive therapy. We sought to determine
whether personality changes that predispose to behavioral disorders arise during
the transition from preclinical AD to mild cognitive impairment (MCI). DESIGN:
Longitudinal observational cohort study. SETTING: Academic medical center.
PARTICIPANTS: Members of an apolipoprotein E (APOE) E4 genetically enriched
cohort of Maricopa County residents who were neuropsychiatrically healthy at
entry (N = 277). Over a mean interval of 7 years, 25 who developed MCI and had
the Neuroticism, Extraversion, and Openness Personality Inventory-Revised (NEO-PI
R) before and during the MCI transition epoch were compared with 252
nontransitioners also with serial NEO-PI-R administrations. INTERVENTION:
Longitudinal administration of the NEO-PI-R and neuropsychological test battery.
MEASUREMENTS: Change in NEO-PI-R factor scores (neuroticism, extraversion,
openness, agreeableness, conscientiousness) from entry to the epoch of MCI
diagnosis or an equivalent follow-up duration in nontransitioners. RESULTS: NEO
PI-R neuroticism T-scores increased significantly more in MCI transitioners than
in nontransitioners (mean 2.9, 95% confidence interval (CI) = 0.9-4.9 vs 0, 95%
CI = -0.7-0.7, P = .02), and openness decreased more in MCI transitioners than in
nontransitioners (-4.8, 95% CI = -7.3 to -2.4 vs -1.0, 95% CI = -1.6 to -0.4, P <
.001). Concurrent subclinical but statistically significant changes in behavioral
scores worsened more in MCI transitioners than nontransitioners for measures of
depression, somatization, irritability, anxiety, and aggressive attitude.
CONCLUSION: Personality and subclinical behavioral changes begin during the
transition from preclinical AD to incident MCI and qualitatively resemble the
clinically manifest behavioral disorders that subsequently arise in individuals
with frank dementia.
PMID- 29341071
TI - Anticholinergic medication for antipsychotic-induced tardive dyskinesia.
AB - BACKGROUND: Antipsychotic (neuroleptic) medication is used extensively to treat
people with serious mental illnesses. However, it is associated with a wide range
of adverse effects, including movement disorders. Because of this, many people
treated with antipsychotic medication also receive anticholinergic drugs in order
to reduce some of the associated movement side-effects. However, there is also a
suggestion from animal experiments that the chronic administration of
anticholinergics could cause tardive dyskinesia. OBJECTIVES: To determine whether
the use or the withdrawal of anticholinergic drugs (benzhexol, benztropine,
biperiden, orphenadrine, procyclidine, scopolamine, or trihexylphenidyl) are
clinically effective for the treatment of people with both antipsychotic-induced
tardive dyskinesia and schizophrenia or other chronic mental illnesses. SEARCH
METHODS: We retrieved 712 references from searching the Cochrane Schizophrenia
Group's Study-Based Register of Trials including the registries of clinical
trials (16 July 2015 and 26 April 2017). We also inspected references of all
identified studies for further trials and contacted authors of trials for
additional information. SELECTION CRITERIA: We included reports identified in the
search if they were controlled trials dealing with people with antipsychotic
induced tardive dyskinesia and schizophrenia or other chronic mental illness who
had been randomly allocated to (a) anticholinergic medication versus placebo (or
no intervention), (b) anticholinergic medication versus any other intervention
for the treatment of tardive dyskinesia, or (c) withdrawal of anticholinergic
medication versus continuation of anticholinergic medication. DATA COLLECTION AND
ANALYSIS: We independently extracted data from included trials and we estimated
risk ratios (RR) with 95% confidence intervals (CIs). We assumed that people who
left early had no improvement. We assessed risk of bias and created a 'Summary of
findings' table using GRADE. MAIN RESULTS: The previous version of this review
included no trials. We identified two trials that could be included from the 2015
and 2017 searches. They randomised 30 in- and outpatients with schizophrenia in
the USA and Germany. Overall, the risk of bias was unclear, mainly due to poor
reporting: allocation concealment was not described; generation of the sequence
was not explicit; studies were not clearly blinded; and outcome data were not
fully reported.Findings were sparse. One study reported on the primary outcomes
and found that significantly more participants allocated to procyclidine
(anticholinergic) had not improved to a clinically important extent compared with
those allocated to isocarboxazid (MAO-inhibitor) after 40 weeks' treatment (1
RCT, n = 20; RR 4.20, 95% CI 1.40 to 12.58; very low quality evidence); that
there was no evidence of a difference in the incidence of any adverse effects (1
RCT, n = 20; RR 0.33, 95% CI 0.02 to 7.32; very low quality evidence); or
acceptability of treatment (measured by participants leaving the study early) (1
RCT, n = 20; RR 0.33, 95% CI 0.02 to 7.32; very low quality evidence). The other
trial compared anticholinergic withdrawal with anticholinergic continuation and
found no evidence of a difference in the incidence of acceptability of treatment
(measured by participants leaving the study early) (1 RCT, n = 10; RR 2.14, 95%
CI 0.11 to 42.52; very low quality evidence).No trials reported on social
confidence, social inclusion, social networks, or personalised quality of life -
outcomes designated important to patients. No studies comparing either i.
anticholinergics with placebo or no treatment, or ii. studies of anticholinergic
withdrawal, were found that reported on the primary outcome 'no clinically
important improvement in TD symptoms and adverse events'. AUTHORS' CONCLUSIONS:
Based on currently available evidence, no confident statement can be made about
the effectiveness of anticholinergics to treat people with antipsychotic-induced
tardive dyskinesia. The same applies for the withdrawal of such medications.
Whether the withdrawal of anticholinergics may benefit people with antipsychotic
induced TD should be evaluated in a parallel-group, placebo-controlled randomised
trial, with adequate sample size and at least 6 weeks of follow-up.
PMID- 29341073
TI - Did You Know?
PMID- 29341074
TI - Back to Basics: The Universal Protocol: 1.4 www.aornjournal.org/content/cme.
PMID- 29341075
TI - Slate of Candidates and Voting Procedures.
PMID- 29341076
TI - Guideline Quick View: Medication Safety.
PMID- 29341077
TI - Assessing Use Errors Related to the Interface Design of Electrosurgical Units.
AB - Medical device use errors, such as instrument connection errors made with
electrosurgical units (ESUs), can lead to adverse events. Current device
acquisition processes at health care facilities do not typically include a
proactive evaluation of use-error risk before device purchase. We conducted an
evaluation to identify ESU user interface design features that can help prevent
or mitigate instrument connection errors during clinical care. Thirty-six current
ESU users participated in the evaluation. We used a randomized crossover design
in which each participant used two ESU models in a simulated OR scenario. We
compared participants' instrument connection accuracy, efficiency, and subjective
feedback regarding the user interface design across the two ESU models. Overall,
we found that the ESU model that incorporated more user interface design
principles resulted in better performance and increased acceptance from users.
Based on the results, we designed a decision-support tool to assess the risk of
instrument connection errors before ESU purchase.
PMID- 29341078
TI - Bylaws Committee 2017-2018 Changes.
PMID- 29341079
TI - Guideline for manual chemical high-level disinfection.
PMID- 29341080
TI - Managing distractions to maintain focus on patients.
PMID- 29341081
TI - Educational Opportunities.
PMID- 29341082
TI - AORN Global Surgical Conference & Expo 2018 Exhibitors.
PMID- 29341084
TI - AORN Nominating and Leadership Development Committee.
PMID- 29341083
TI - Factors Contributing to Perioperative Medication Errors: A Systematic Literature
Review: 2.1 www.aornjournal.org/content/cme.
PMID- 29341086
TI - Clinical Issues-January 2018: 1.2 www.aornjournal.org/content/cme.
PMID- 29341087
TI - July Syndrome.
PMID- 29341088
TI - Evidence appraisal of Boonchan T, Wilasrusmee C, McEvoy M, Attia J, Thakkinstian
A. Network meta-analysis of antibiotic prophylaxis for prevention of surgical
site infection after groin hernia surgery. Br J Surg. 2017;104(2):e106-e117.
doi:10.1002/bjs.10441.
PMID- 29341089
TI - Candidate Biographical Information and Election Statements.
PMID- 29341090
TI - Annual conference promises new learning opportunities.
PMID- 29341091
TI - The Importance of Understanding Health Literacy for Perioperative Patient Safety.
PMID- 29341093
TI - AORN Board of Directors.
PMID- 29341092
TI - New Editor-in-Chief for the AORN Journal.
PMID- 29341095
TI - AORN Global Surgical Conference & Expo 2018 Speaker Interviews.
PMID- 29341094
TI - Implementing a Perioperative Nursing Student Summer Internship.
AB - Using qualitative research and a collaborative academic service partnership, we
created an innovative 120-hour perioperative nursing summer internship for eight
undergraduate nursing students in 2016. Recognizing that perioperative exposure
is limited in the traditional baccalaureate program, this unpaid internship
served to clarify student perceptions of perioperative nursing care and encourage
graduates to meet perioperative workforce demands. We based the theoretical and
practical student learning experiences on the AORN Periop 101 learning modules
and included faculty-led discussions, student journaling, and onsite precepted
clinical activities. Evaluation data revealed that students achieved an enhanced
awareness of perioperative nursing, and a majority of the participants expressed
a desire to enter the perioperative field after graduation. We suggest that
stakeholders continue to strategize ways to maximize educational preparation to
address the evolving health care market supply and demand.
PMID- 29341097
TI - A Postprocedure Wrap-up Tool for Improving OR Communication and Performance.
AB - In 2015, perioperative nursing staff members at a community hospital designed and
implemented a tool to help improve communication and performance. Our
postprocedure wrap-up tool and its follow-up process have allowed us to achieve
improvements in both efficiency and staff member satisfaction. By implementing a
process to document problems as they occur and quickly transmit information to
the staff members who are best able to correct these issues, we greatly improved
our workflow. Furthermore, by inputting information into spreadsheets using
problem codes, thereby replacing anecdotal information with hard data, we
targeted areas that needed improvement and used that information for budget
planning, training, and allocating resources. Enlisting the input of all members
of the surgical team allowed us to identify the root causes of issues that
interfered with the staff members' ability to provide efficient, safe, and
reliable patient care.
PMID- 29341098
TI - Embrace Action: Make Personal and Professional Resolutions.
PMID- 29341099
TI - Ventriculoperitoneal shunt.
PMID- 29341100
TI - Underdiagnosis of Influenza Virus Infection in Hospitalized Older Adults.
AB - OBJECTIVES: To describe factors associated with provider-ordered influenza
testing in hospitalized older adults. DESIGN: Information on participant
demographics, symptoms, and provider-ordered influenza testing were collected by
questionnaire and chart review. We conducted prospective laboratory-based
surveillance using reverse-transcriptase polymerase chain reaction (RT-PCR), the
criterion standard for diagnosis of influenza, to determine how participant
characteristics and provider-ordered testing affected accurate influenza
diagnosis. SETTING: One academic and three community hospitals in Davidson
County, Tennessee. PARTICIPANTS: Adults aged 18 and older with acute respiratory
illness or nonlocalizing fever (N=1,422). MEASUREMENTS: We compared
characteristics of participants with and without provider-ordered testing for
influenza using the Wilcoxon test and Pearson chi-square test. Multivariable
logistic regression models were used to identify factors predictive of provider
ordered influenza testing. RESULTS: Twenty-eight percent (399/1,422) of
participants had provider-ordered influenza testing. Participants who were tested
were younger than those not tested (58 +/- 18 vs 66 +/- 15, p<.001) and more
likely to have influenza-like illness (ILI) (71% vs 49%, p<.001). ILI decreased
with increasing age (aged 18-49, 63%; aged 50-64, 60%; aged >=65, 48%). ILI and
younger age were independent predictors of provider-ordered testing. Of the 136
participants with influenza confirmed using RT-PCR, ILI was the only significant
predictor of provider-ordered testing (adjusted odds ratio=3.43, 95% confidence
interval=1.22-9.70). CONCLUSION: Adults aged 65 and older hospitalized with fever
or respiratory symptoms during influenza season are less likely to undergo a
provider-ordered influenza test than younger adults. Some, but not all, of this
disparity is due to a lower likelihood of ILI. Further strategies are needed to
increase clinician awareness and testing in this vulnerable group.
PMID- 29341101
TI - An overview of confounding. Part 2: how to identify it and special situations.
AB - Confounding biases study results when the effect of the exposure on the outcome
mixes with the effects of other risk and protective factors for the outcome that
are present differentially by exposure status. However, not all differences
between the exposed and unexposed group cause confounding. Thus, sources of
confounding must be identified before they can be addressed. Confounding is
absent in an ideal study where all of the population of interest is exposed in
one universe and is unexposed in a parallel universe. In an actual study, an
observed unexposed population represents the unobserved parallel universe.
Thinking about differences between this substitute population and the unexposed
parallel universe helps identify sources of confounding. These differences can
then be represented in a diagram that shows how risk and protective factors for
the outcome are related to the exposure. Sources of confounding identified in the
diagram should be addressed analytically and through study design. However,
treating all factors that differ by exposure status as confounders without
considering the structure of their relation to the exposure can introduce bias.
For example, conditions affected by the exposure are not confounders. There are
also special types of confounding, such as time-varying confounding and unfixable
confounding. It is important to evaluate carefully whether factors of interest
contribute to confounding because bias can be introduced both by ignoring
potential confounders and by adjusting for factors that are not confounders. The
resulting bias can result in misleading conclusions about the effect of the
exposure of interest on the outcome.
PMID- 29341102
TI - Fungal kerion of the vulva.
PMID- 29341103
TI - An overview of confounding. Part 1: the concept and how to address it.
AB - Confounding is an important source of bias, but it is often misunderstood. We
consider how confounding occurs and how to address confounding using examples.
Study results are confounded when the effect of the exposure on the outcome,
mixes with the effects of other risk and protective factors for the outcome. This
problem arises when these factors are present to different degrees among the
exposed and unexposed study participants, but not all differences between the
groups result in confounding. Thinking about an ideal study where all of the
population of interest is exposed in one universe and is unexposed in a parallel
universe helps to distinguish confounders from other differences. In an actual
study, an observed unexposed population is chosen to stand in for the unobserved
parallel universe. Differences between this substitute population and the
parallel universe result in confounding. Confounding by identified factors can be
addressed analytically and through study design, but only randomization has the
potential to address confounding by unmeasured factors. Nevertheless, a given
randomized study may still be confounded. Confounded study results can lead to
incorrect conclusions about the effect of the exposure of interest on the
outcome.
PMID- 29341104
TI - Hair cortisol is elevated in patients with erythropoietic protoporphyria and
correlates with body mass index and quality of life.
PMID- 29341105
TI - Metabolomic characterization of human hippocampus from drug-resistant epilepsy
with mesial temporal seizure.
AB - OBJECTIVE: Within a complex systems biology perspective, we wished to assess
whether hippocampi with established neuropathological features have distinct
metabolome. Apparently normal hippocampi with no signs of sclerosis (noHS), were
compared to hippocampal sclerosis (HS) type 1 (HS1) and/or type 2 (HS2).
Hippocampus metabolome from patients with epilepsy-associated neuroepithelial
tumors (EANTs), namely, gangliogliomas (GGs) and dysembryoplastic neuroepithelial
tumors (DNTs), was also compared to noHS epileptiform tissue. METHODS: All
patients underwent standardized temporal lobectomy. We applied 1 H high
resolution magic angle spinning nuclear magnetic resonance (HRMAS NMR)
spectroscopy to 48 resected human hippocampi. NMR spectra allowed quantification
of 21 metabolites. Data were analyzed using multivariate analysis based on mutual
information. RESULTS: Clear distinct metabolomic profiles were observed between
all studied groups. Sixteen and 18 expected metabolite levels out of 21 were
significantly different for HS1 and HS2, respectively, when compared to noHS.
Distinct concentration variations for glutamine, glutamate, and N-acetylaspartate
(NAA) were observed between HS1 and HS2. Hippocampi from GG and DNT patients
showed 7 and 11 significant differences in metabolite concentrations when
compared to the same group, respectively. GG and DNT had a clear distinct
metabolomic profile, notably regarding choline compounds, glutamine, glutamate,
aspartate, and taurine. Lactate and acetate underwent similar variations in both
groups. SIGNIFICANCE: HRMAS NMR metabolomic analysis was able to disentangle
metabolic profiles between HS, noHS, and epileptic hippocampi associated with
EANT. HRMAS NMR metabolomic analysis may contribute to a better identification of
abnormal biochemical processes and neuropathogenic combinations underlying mesial
temporal lobe epilepsy.
PMID- 29341106
TI - The effect of surgery on subsequent pregnancy outcomes among patients with
cesarean scar diverticulum.
AB - OBJECTIVE: To determine whether surgical treatment of cesarean scar diverticulum
(CSD) reduced adverse outcomes during the subsequent pregnancy. METHODS: A
retrospective observational study was conducted using the medical records of
pregnant women with CSD who attended a single hospital in Hangzhou, China,
between January 1, 2014, and December 31, 2016. Baseline characteristics and
pregnancy outcomes were compared between the surgery group and the no surgery
group. RESULTS: There were 106 patients included in the study, 83 in the surgery
group and 23 in the no surgery group. The CSD size was greater in all dimensions
for the surgery group versus the no surgery group: length (P<0.001), width
(P=0.001), and depth (P=0.030). The remaining myometrium was thinner among women
in the surgery group than those in the no surgery group (P=0.011). In all, 76
(91.6%) women in the surgery group were symptomatic. The incidence of live
delivery pregnancy was higher (P=0.033) and the incidence of cesarean scar
pregnancy was lower (P=0.019) in the surgery group versus the no surgery group.
Surgery increased the thickness of the lower uterine segment (P<0.001); however,
it did not reduce the risks of placenta previa or placenta accreta (P=0.683) and
uterine dehiscence or uterine rupture (P=0.458). CONCLUSION: Surgical
intervention reduced the incidence of cesarean scar pregnancy and increased the
number of live deliveries.
PMID- 29341107
TI - Anthropogenic nitrogen deposition ameliorates the decline in tree growth caused
by a drier climate.
AB - Most forest ecosystems are simultaneously affected by concurrent global change
drivers. However, when assessing these effects, studies have mainly focused on
the responses to single factors and have rarely evaluated the joined effects of
the multiple aspects of environmental change. Here, we analyzed the combined
effects of anthropogenic nitrogen (N) deposition and climatic conditions on the
radial growth of Acer saccharum, a dominant tree species in eastern North
American forests. We capitalized on a long-term N deposition study, replicated
along a latitudinal gradient, that has been taking place for more than 20 yr. We
analyzed tree radial growth as a function of anthropogenic N deposition (ambient
and experimental addition) and of summer temperature and soil water conditions.
Our results reveal that experimental N deposition enhances radial growth of this
species, an effect that was accentuated as temperature increased and soil water
became more limiting. The spatial and temporal extent of our data also allowed us
to assert that the positive effects of growing under the experimental N
deposition are likely due to changes in the physiological performance of this
species, and not due to the positive correlation between soil N and soil water
holding capacity, as has been previously speculated in other studies. Our
simulations of tree growth under forecasted climate scenarios specific for this
region also revealed that although anthropogenic N deposition may enhance tree
growth under a large array of environmental conditions, it will not mitigate the
expected effects of growing under the considerably drier conditions
characteristic of our most extreme climatic scenario.
PMID- 29341108
TI - Characteristics of tendon derived stem cells according to different factors to
induce the tendinopathy.
AB - Tendon derived stem cells (TDSCs) have been used as a therapeutic agent and as a
healing marker. However, there has been no study about the characteristics of
TDSCs extracted from tendinopathic tendon tissues. The aim of this study was to
find the different characteristics of TDSCs according to the factors to induce
the tendinopathy. Five- and fifteen-week old Sprague Dawley rats were used for
this study and chemically-induced and injury-induced tendinopathy models were
made depending on the age of the animal for different types of tendinopathy.
TDSCs from chemically-induced tendinopathy showed markedly low proliferation
compared to those from age-matched normal control and injury-induced
tendinopathy. In addition, TDSCs from chemically-induced tendinopathy progressed
to osteogenesis under an osteogenic differentiation environment more than those
from other groups. In contrast, TDSCs from injury-induced tendinopathy showed
markedly high proliferation and high expression of type III collagen and alpha
SMA compared to other groups. Adipogenic potentials in TDSCs from injury-induced
tendinopathy were also higher. These different characteristics might be helpful
in the development new therapeutic agents for tendon regeneration according to
different factors to induce the tendinopathy.
PMID- 29341109
TI - The prescribable drugs with efficacy in experimental epilepsies (PDE3) database
for drug repurposing research in epilepsy.
AB - OBJECTIVE: Current antiepileptic drugs (AEDs) have several shortcomings. For
example, they fail to control seizures in 30% of patients. Hence, there is a need
to identify new AEDs. Drug repurposing is the discovery of new indications for
approved drugs. This drug "recycling" offers the potential of significant savings
in the time and cost of drug development. Many drugs licensed for other
indications exhibit antiepileptic efficacy in animal models. Our aim was to
create a database of "prescribable" drugs, approved for other conditions, with
published evidence of efficacy in animal models of epilepsy, and to collate data
that would assist in choosing the most promising candidates for drug repurposing.
METHODS: The database was created by the following: (1) computational literature
mining using novel software that identifies Medline abstracts containing the name
of a prescribable drug, a rodent model of epilepsy, and a phrase indicating
seizure reduction; then (2) crowdsourced manual curation of the identified
abstracts. RESULTS: The final database includes 173 drugs and 500 abstracts. It
is made freely available at www.liverpool.ac.uk/D3RE/PDE3. The database is
reliable: 94% of the included drugs have corroborative evidence of efficacy in
animal models (for example, evidence from multiple independent studies). The
database includes many drugs that are appealing candidates for repurposing, as
they are widely accepted by prescribers and patients-the database includes half
of the 20 most commonly prescribed drugs in England-and they target many proteins
involved in epilepsy but not targeted by current AEDs. It is important to note
that the drugs are of potential relevance to human epilepsy-the database is
highly enriched with drugs that target proteins of known causal human epilepsy
genes (Fisher's exact test P-value < 3 * 10-5 ). We present data to help
prioritize the most promising candidates for repurposing from the database.
SIGNIFICANCE: The PDE3 database is an important new resource for drug repurposing
research in epilepsy.
PMID- 29341110
TI - Eurogin roadmap 2017: Triage strategies for the management of HPV-positive women
in cervical screening programs.
AB - Cervical cancer screening will rely, increasingly, on HPV testing as a primary
screen. The requirement for triage tests which can delineate clinically
significant infection is thus prescient. In this EUROGIN 2017 roadmap,
justification behind the most evidenced triages is outlined, as are challenges
for implementation. Cytology is the triage with the most follow-up data; the
existence of an HR-HPV-positive, cytology-negative group presents a challenge and
retesting intervals for this group (and choice of retest) require careful
consideration. Furthermore, cytology relies on subjective skills and while
adjunctive dual-staining with p16/Ki67 can mitigate inter-operator/-site
disparities, clinician-taken samples are required. Comparatively, genotyping and
methylation markers are objective and are applicable to self-taken samples,
offering logistical advantages including in low and middle income settings.
However, genotyping may have diminishing returns in immunised populations and
type(s) included must balance absolute risk for disease to avoid low specificity.
While viral and cellular methylation markers show promise, more prospective data
are needed in addition to refinements in automation. Looking forward, systems
that detect multiple targets concurrently such as next generation sequencing
platforms will inform the development of triage tools. Additionally, multistep
triage strategies may be beneficial provided they do not create complex,
unmanageable pathways. Inevitably, the balance of risk to cost(s) will be key in
decision making, although defining an acceptable risk will likely differ between
settings. Finally, given the significant changes to cervical screening and the
variety of triage strategies, appropriate education of both health care providers
and the public is essential.
PMID- 29341111
TI - Variation and drivers of airflow patterns associated with olfactory concealment
and habitat selection.
AB - Many terrestrial predators rely on olfaction to detect prey; therefore, prey
should select habitat to reduce detectability of their odor cues. One way prey
can potentially conceal their odor is by selecting locations with high turbulence
and/or updrafts, conditions that disperse odor plumes and make odor sources
difficult to locate. However, it is unclear how these conditions vary among
vegetation cover types and which vegetative features drive them. We assessed
variation and drivers of variables hypothesized to influence olfactory
concealment (turbulence intensity and airflow slope) and experimentally evaluated
whether these variables indeed influence predator detection of simulated prey.
Specifically, we compared vegetation patch-scale values of turbulence intensity
and airflow slope among grassland, shrubland, and forest and assessed
relationships among these airflow variables and local-scale vegetative features
within each vegetation type. Additionally, we experimentally investigated the
importance of turbulence intensity, airflow slope, and visual concealment for
predicting predator detection of scented quail eggs. In all vegetation types, we
documented high variability in airflow conditions. At the patch scale, turbulence
intensity was greater in shrubland and grassland than in forest, and updrafts
were most common in shrubland whereas downdrafts were most common in grassland.
Grassland was the only vegetation type with strong relationships among turbulence
intensity and local vegetation features; both visual concealment and vegetation
height were positively related to turbulence intensity. Additionally, persistence
of scented quail eggs in grassland was best predicted by turbulence intensity;
egg persistence increased with turbulence intensity. Our characterization of
differences in olfactory variables among vegetation types provides an important
step towards building a clearer understanding of olfactory landscapes. Further,
our observation of both patch- and local-scale variation in olfactory variables
suggests that prey can potentially select for olfactory concealment at multiple
scales. We hypothesize that olfactory concealment provided by high levels of
turbulence intensity is an important component of cover in grassland, and that in
grassland/shrubland landscapes, prey selection of shrubland patches reduces odor
detectability. Our finding of a positive relationship between turbulence
intensity and visual concealment also suggests that olfactory concealment may be
a previously underappreciated confounding factor in studies of habitat selection.
PMID- 29341112
TI - Conditionally reprogrammed cells (CRC) methodology does not allow the in vitro
expansion of patient-derived primary and metastatic lung cancer cells.
AB - Availability of tumor and non-tumor patient-derived models would promote the
development of more effective therapeutics for non-small cell lung cancer
(NSCLC). Recently, conditionally reprogrammed cells (CRC) methodology
demonstrated exceptional potential for the expansion of epithelial cells from
patient tissues. However, the possibility to expand patient-derived lung cancer
cells using CRC protocols is controversial. Here, we used CRC approach to expand
cells from non-tumoral and tumor biopsies of patients with primary or metastatic
NSCLC as well as pulmonary metastases of colorectal or breast cancers. CRC
cultures were obtained from both tumor and non-malignant tissues with
extraordinary high efficiency. Tumor cells were tracked in vitro through
tumorigenicity assay, monitoring of tumor-specific genetic alterations and marker
expression. Cultures were composed of EpCAM+ lung epithelial cells lacking
tumorigenic potential. NSCLC biopsies-derived cultures rapidly lost patient
specific genetic mutations or tumor antigens. Similarly, pulmonary metastases of
colon or breast cancer generated CRC cultures of lung epithelial cells. All CRC
cultures examined displayed epithelial lung stem cell phenotype and function. In
contrast, brain metastatic lung cancer biopsies failed to generate CRC cultures.
In conclusion, patient-derived primary and metastatic lung cancer cells were
negatively selected under CRC conditions, limiting the expansion to non-malignant
lung epithelial stem cells from either tumor or non-tumor tissue sources. Thus,
CRC approach cannot be applied for direct therapeutic testing of patient lung
tumor cells, as the tumor-derived CRC cultures are composed of (non-tumoral)
airway basal cells.
PMID- 29341113
TI - Prospective emotion enables episodic prospection to shift time preference.
AB - The episodic effect suggests that episodic prospection (imagining future events)
can effectively reduce time discounting, the propensity to discount the value of
delayed rewards relative to immediate ones. However, less clear is how episodic
prospection modulates time preference. As engagement in episodic prospection
usually evokes prospective emotions, it was proposed that episodic prospection
might work by inducing prospective emotions. Although one previous study has
attempted to provide evidence to the emotional account of the episodic effect,
shortcomings in its experimental design make its conclusion questionable. In this
study, we replicated previous experimental design with improvements to further
test the effects of prospective emotion on time preference. By manipulating the
emotional valency associated with episodic prospection in a delay discounting
task, we found that positive episodic prospection attenuated time discounting;
negative episodic prospection exacerbated time discounting; and episodic
prospection did not shift time preference when prospective emotion is removed.
These results were essentially identical to the result of the previous study.
Together, these studies suggested that the effects of episodic prospection
depended on prospective emotion. Thus, one cannot ignore prospective emotion if
counting on episodic prospection to combat humans' impulsive behaviours.
PMID- 29341114
TI - Recombinant human hepatocyte growth factor provides protective effects in
cerulein-induced acute pancreatitis in mice.
AB - Acute pancreatitis is a multifactorial disease associated with profound changes
of the pancreas induced by release of digestive enzymes that lead to increase in
proinflammatory cytokine production, excessive tissue necrosis, edema, and
bleeding. Elevated levels of hepatocyte growth factor (HGF) and its receptor c
Met have been observed in different chronic and acute pancreatic diseases
including experimental models of acute pancreatitis. In the present study, we
investigated the protective effects induced by the recombinant human HGF in a
mouse model of cerulein-induced acute pancreatitis. Pancreatitis was induced by 8
hourly administrations of supramaximal cerulein injections (50 ug/kg, ip). HGF
treatment (20 ug/kg, iv), significantly attenuated lipase content and amylase
activity in serum as well as the degree inflammation and edema overall leading to
less severe histologic changes such as necrosis, induced by cerulein. Protective
effects of HGF were associated with activation of pro-survival pathways such as
Akt, Erk1/2, and Nrf2 and increase in executor survival-related proteins and
decrease in pro-apoptotic proteins. In addition, ROS content and lipid
peroxidation were diminished, and glutathione synthesis increased in pancreas.
Systemic protection was observed by lung histology. In conclusion, our data
indicate that HGF exerts an Nrf2 and glutathione-mediated protective effect on
acute pancreatitis reflected by a reduction in inflammation, edema, and oxidative
stress.
PMID- 29341115
TI - Non-volant mammals from the Upper Parana River Basin: a data set from a critical
region for conservation in Brazil.
AB - The data set represents the first attempt at a large-scale inventory of non
volant mammals, with potential applications to performing macroecological
studies, developing conservation strategies, and undertaking population and
community ecology research, but also to evaluate the ecological consequences of
fragmentation and defaunation. Our objectives for compiling these data were to
summarize information about inventories of non-volant mammals in the critically
important area of the Upper Parana River Basin by focusing on species richness
and index of frequency of occurrence and to identify gaps in knowledge regarding
non-volant mammal communities in order to guide future sampling efforts. The data
set comprises studies on communities of non-volant mammals from 52 locations
covering more than 1,000 km2 and comprises portion of four Brazilian states in
the Upper Parana River Basin. We listed 81 species of non-volant mammals
distributed among 58 genera, 22 families, and 9 orders. Rodentia (28 species) was
the richest order, followed by Carnivora (17 spp.) and Didelphimorphia (15 spp.).
The richest family was Cricetidae (20 spp.), followed by Didelphidae (15 spp.),
and Dasypodidae and Felidae (six spp.). Considering national conservation status,
one species are considered endangered and 16 vulnerable. Considering global
conservation status, 7 species are considered vulnerable, 10 are considered near
threatened, and 6 are data deficient. According to the index of frequency of
occurrence, Myrmecophaga tridactyla was the most frequent species, occurring at
88.64% of all sites, while 25 species were considered very restricted, occurring
in just 2.56% of all sites. In general, the non-volant mammal fauna was composed
of mainly very restricted (VR, 25 species) and localized species (L, 25 species),
which account for 61.7% of the known species, while 38.3% are restricted (R, 8
species), common (C, 16 species), and widespread (W, 7 species). Seven marsupials
and five small rodents had their distributions extended in the central-south of
Brazil. All of these species are considered data deficient or threatened, which
highlights the importance of these records. No copyright restrictions are
associated with the use of this data set. Please cite this data paper when the
data are used in publications. We also request that researchers and teachers
inform us of how they are using the data.
PMID- 29341116
TI - Rare missense mutations in RECQL and POLG associate with inherited predisposition
to breast cancer.
AB - Several known breast cancer susceptibility genes with moderate-to-high risk
alleles encode proteins involved in DNA damage response (DDR). As these explain
less than half of the hereditary breast cancer cases, additional predisposing
alleles are likely to be discovered. Many of the previous studies utilizing
massive parallel sequencing have focused on the protein-truncating variants, and
the role of rare missense mutations has remained poorly addressed. To identify
novel susceptibility factors, we have systematically analyzed the data from our
parallel sequencing of 796 DDR genes in 189 Northern Finnish hereditary breast
cancer patients for rare missense variants, predicted as deleterious. Thirty-five
variants were studied here for the disease association using Finnish breast
cancer case (n = 492-2,035) and control (n = 277-1,539) cohorts. As a result, two
missense variants in genes involved in DNA replication, RECQL p.I156M and POLG
p.L392V, the former involving genomic and the latter mitochondrial DNA
replication, showed significant association with risk of breast cancer. Rare
RECQL p.I156M allele was observed in breast cancer cases only (6/1,946, 0.3%, p =
0.043), whereas POLG p.L392V was two times more frequent in breast cancer cases
(53/2,238, 2.4%) compared to controls (18/1,539, 1.2%, OR = 2.1, 95% CI 1.2-3.5,
p = 0.010). Based on the current genetic data, both RECQL p.I156M and POLG
p.L392V represent novel breast cancer predisposing alleles.
PMID- 29341117
TI - HOXD-AS1/miR-130a sponge regulates glioma development by targeting E2F8.
AB - Glioma development is an extremely complex process with changes occurring in
numerous genes. HOXD antisense growth-associated long noncoding RNA (HOXD-AS1),
an important long noncoding RNA (lncRNA), is known to regulate metastasis-related
gene expression in bladder cancer, ovarian cancer and neuroblastoma. Here, we
elucidated the function and possible molecular mechanisms of lncRNA HOXD-AS1 in
human glioma cells. Our results proved that HOXD-AS1 expression was upregulated
in glioma tissues and in glioma cell lines. HOXD-AS1 overexpression promoted cell
migration and invasion in vitro, whereas knockdown of HOXD-AS1 expression
repressed these cellular processes. Mechanistic studies further revealed that
HOXD-AS1 could compete with the transcription factor E2F8 to bind with miR-130a,
thus affecting E2F8 expression. Additionally, reciprocal repression was observed
between HOXD-AS1 and miR-130a, and miR-130a mediated the tumor-suppressive
effects of HOXD-AS1 knockdown. Taken together, these results provide a
comprehensive analysis of the role of HOXD-AS1 in glioma cells and offer
important clues to understand the key roles of competing endogenous RNA (ceRNA)
mechanisms in human glioma.
PMID- 29341119
TI - Time to Settle the Fracking Controversy.
PMID- 29341120
TI - Trajectories of Infants' Biobehavioral Development: Timing and Rate of A-Not-B
Performance Gains and EEG Maturation.
AB - This study examined how timing (i.e., relative maturity) and rate (i.e., how
quickly infants attain proficiency) of A-not-B performance were related to
changes in brain activity from age 6 to 12 months. A-not-B performance and
resting EEG (electroencephalography) were measured monthly from age 6 to 12
months in 28 infants and were modeled using logistic and linear growth curve
models. Infants with faster performance rates reached performance milestones
earlier. Infants with faster rates of increase in A-not-B performance had lower
occipital power at 6 months and greater linear increases in occipital power. The
results underscore the importance of considering nonlinear change processes for
studying infants' cognitive development as well as how these changes are related
to trajectories of EEG power.
PMID- 29341118
TI - Inhibition of the Fibrinogen-Like Protein 2:FcgammaRIIB/RIII immunosuppressive
pathway enhances antiviral T-cell and B-cell responses leading to clearance of
lymphocytic choriomeningitis virus clone 13.
AB - Persistent viruses evade immune detection by interfering with virus-specific
innate and adaptive antiviral immune responses. Fibrinogen-like protein-2 (FGL2)
is a potent effector molecule of CD4+ CD25+ FoxP3+ regulatory T cells and
exerts its immunosuppressive activity following ligation to its cognate receptor,
FcgammaRIIB/RIII. The role of FGL2 in the pathogenesis of chronic viral infection
caused by lymphocytic choriomeningitis virus clone-13 (LCMV cl-13) was assessed
in this study. Chronically infected fgl2+/+ mice had increased plasma levels of
FGL2, with reduced expression of the maturation markers, CD80, CD86 and MHC-II on
macrophages and dendritic cells and impaired production of neutralizing antibody.
In contrast, fgl2-/- mice or fgl2+/+ mice that had been pre-treated with
antibodies to FGL2 and FcgammaRIIB/RIII and then infected with LCMV cl-13
developed a robust CD4+ and CD8+ antiviral T-cell response, produced high titred
neutralizing antibody to LCMV and cleared LCMV. Treatment of mice with
established chronic infection with antibodies to FGL2 and FcgammaRIIB/RIII was
shown to rescue the number and functionality of virus-specific CD4+ and CD8+ T
cells with reduced total and virus-specific T-cell expression of programmed cell
death protein 1 leading to viral clearance. These results demonstrate an
important role for FGL2 in viral immune evasion and provide a rationale to target
FGL2 to treat patients with chronic viral infection.
PMID- 29341121
TI - Violence, Guns, and Suicide in New Orleans: Results from a Qualitative Study of
Recent Suicide Decedents.
AB - Many Americans own guns to protect themselves against other people, but there is
evidence that both victimization and gun access increase suicide risk. We
conducted qualitative interviews with informants of 17 suicide cases in New
Orleans of the 60 who died between January 2015 and April 2016 to understand the
relationship between past trauma, gun access and storage, and suicide. Nine cases
had experienced a past trauma, including three who had recently had a family
member killed by homicide. Eight died via firearm; of those, seven owned the guns
they used to take their lives and stored them locked (but loaded) at home or in
their cars. Preventing community violence and addressing its sequelae may be
important for reducing suicides. A multi-pronged strategy consisting of policies,
education, and marketing will likely be needed to address the risk of suicide
conferred by gun access.
PMID- 29341123
TI - Do longer root hairs improve phosphorus uptake? Testing the hypothesis with
transgenic Brachypodium distachyon lines overexpressing endogenous RSL genes.
AB - Mutants without root hairs show reduced inorganic orthophosphate (Pi) uptake and
compromised growth on soils when Pi availability is restricted. What is less
clear is whether root hairs that are longer than wild-type provide an additional
benefit to phosphorus (P) nutrition. This was tested using transgenic
Brachypodium lines with longer root hairs. The lines were transformed with the
endogenous BdRSL2 and BdRSL3 genes using either a constitutive promoter or a root
hair-specific promoter. Plants were grown for 32 d in soil amended with various
Pi concentrations. Plant biomass and P uptake were measured and genotypes were
compared on the basis of critical Pi values and P uptake per unit root length.
Ectopic expression of RSL2 and RSL3 increased root hair length three-fold but
decreased plant biomass. Constitutive expression of BdRSL2, but not expression of
BdRSL3, consistently improved P nutrition as measured by lowering the critical Pi
values and increasing Pi uptake per unit root length. Increasing root hair length
through breeding or biotechnology can improve P uptake efficiency if the
pleotropic effects on plant biomass are avoided. Long root hairs, alone, appear
to be insufficient to improve Pi uptake and need to be combined with other traits
to benefit P nutrition.
PMID- 29341122
TI - Impacts of Methane on Carbon Dioxide Storage in Brine Formations.
AB - In the context of geological carbon sequestration (GCS), carbon dioxide (CO2 ) is
often injected into deep formations saturated with a brine that may contain
dissolved light hydrocarbons, such as methane (CH4 ). In this multicomponent
multiphase displacement process, CO2 competes with CH4 in terms of dissolution,
and CH4 tends to exsolve from the aqueous into a gaseous phase. Because CH4 has a
lower viscosity than injected CO2 , CH4 is swept up into a 'bank' of CH4 -rich
gas ahead of the CO2 displacement front. On the one hand, this may provide a
useful tracer signal of an approaching CO2 front. On the other hand, the
emergence of gaseous CH4 is undesirable because it poses a leakage risk of a far
more potent greenhouse gas than CO2 if the cap rock is compromised. Open
fractures or faults and wells could result in CH4 contamination of overlying
groundwater aquifers as well as surface emissions. We investigate this process
through detailed numerical simulations for a large-scale GCS pilot project (near
Cranfield, Mississippi) for which a rich set of field data is available. An
accurate cubic-plus-association equation-of-state is used to describe the non
linear phase behavior of multiphase brine-CH4 -CO2 mixtures, and breakthrough
curves in two observation wells are used to constrain transport processes. Both
field data and simulations indeed show the development of an extensive plume of
CH4 -rich (up to 90 mol%) gas as a consequence of CO2 injection, with important
implications for the risk assessment of future GCS projects.
PMID- 29341124
TI - Metric Assessment of the Pubic Bone Using Known and Novel Data Points for Sex
Estimation.
AB - Biological sex estimation of skeletal remains is essential in forensic and
archaeological analyses. Anthropologists most often use the pelvis, which is the
most sexually dimorphic element both morphologically and metrically. While
nonmetric pubic bone features have been studied extensively, few metric studies
have examined this individual bone for dimorphism. For this study, three
observers examined three previously identified and ten novel measurements of the
pubic body on a modern sample of isolated pubic bones from the Maricopa County
Forensic Science Center (FSC), in Phoenix, Arizona (n = 400). A relationship
between pubic body measurements and biological sex was demonstrated, with
significant correlations. Discriminant function analyses found that five
measurements, four of which were novel, discriminated between males (89%) and
females (86%). Observer experience level did not significantly impact the
results. These five measurements were reliable and show promise for inclusion in
metric methods for assessment of sex.
PMID- 29341125
TI - Gut microbiota and probiotics: novel immune system modulators in myasthenia
gravis?
AB - Gut microorganisms (microbiota) live in symbiosis with the host and influence
human nutrition, metabolism, physiology, and immune development and function. The
microbiota prevents pathogen infection to the host, and in turn the host provides
a niche for survival. The alteration of gut bacteria composition (dysbiosis)
could contribute to the development of immune-mediated diseases by influencing
the immune system activation and driving the pro- and anti-inflammatory responses
in order to promote or counteract immune reactions. Probiotics are nonpathogenic
microorganisms able to interact with the gut microbiota and provide health
benefits; their use has recently been exploited to dampen immunological response
in several experimental models of autoimmune diseases. Here, we focus on the
relationships among commensal bacteria, probiotics, and the gut, describing the
main interactions occurring with the immune system and recent data supporting the
clinical efficacy of probiotic administration in rheumatoid arthritis, multiple
sclerosis, and myasthenia gravis (MG) animal models. The encouraging results
suggest that selected strains of probiotics should be evaluated in clinical
trials as adjuvant therapy to restore the disrupted tolerance in myasthenia
gravis.
PMID- 29341126
TI - Size Assessment of the Gray Reef Shark Carcharhinus amblyrhynchos Inferred from
Teeth Marks on Human Wounds.
AB - An accurate assessment of the biting shark size is paramount for better
understanding the agonistic behavior of a species toward humans. The gray reef
shark is involved in many accidental bites. Based on the capture of 35 gray
sharks, we calculated the algorithm that allows the assessment of the shark size,
through the interdental distance (IDD) inferred from teeth marks on human wounds.
Our results show a negative allometric relationship and that IDD calculated from
imprints perpetrated by the upper jaw are globally similar with those from the
lower jaw, in spite of heterodonty. We applied our findings to two cases of
accidental bites by this species. Both of the victims had declared that the shark
length was "at least 2 m". Based on our algorithm, the assessment of the shark TL
was approx. 180 and 160 cm, respectively, which correspond to an overestimation
of >=20% by the victims.
PMID- 29341127
TI - Discrimination of Geographical Origin of Asian Garlic Using Isotopic and Chemical
Datasets under Stepwise Principal Component Analysis.
AB - Isotopic compositions of delta2 H, delta18 O, delta13 C, and delta15 N and
concentrations of 22 trace elements from garlic samples were analyzed and
processed with stepwise principal component analysis (PCA) to discriminate
garlic's country of origin among Asian regions including South Korea, Vietnam,
Taiwan, and China. Results indicate that there is no single trace-element
concentration or isotopic composition that can accomplish the study's purpose and
the stepwise PCA approach proposed does allow for discrimination between
countries on a regional basis. Sequentially, Step-1 PCA distinguishes garlic's
country of origin among Taiwanese, South Korean, and Vietnamese samples; Step-2
PCA discriminates Chinese garlic from South Korean garlic; and Step-3 and Step-4
PCA, Chinese garlic from Vietnamese garlic. In model tests, countries of origin
of all audit samples were correctly discriminated by stepwise PCA. Consequently,
this study demonstrates that stepwise PCA as applied is a simple and effective
approach to discriminating country of origin among Asian garlics.
PMID- 29341128
TI - Study on the Method Used to Display Self-fading Lines and Erasable Lines.
AB - Two new kinds of writing tools are popular in China's market. One is a self
fading pen, and another is an erasable pen. The ink of the two kinds of writing
tools has a remarkable characteristic that it can gradually fade or disappear
under heat or be rubbed off. How to reveal the disappeared written lines is a
very important question for document examiners. In this article, three series of
ink line samples were made with five types of self-fading pens, 18 types of
erasable pens, and three types of papers. Temperature, humidity, and lighting are
known as influential factors of the process, and the effect of fading was
examined. Luminescence, ultraviolet (UV), sidelight, electrostatic indentation
development,low temperature, and solution revealing methods are found to be
effective methods used to reveal the disappeared written lines. The best
operating conditions for each method were obtained from the conducted
experiments.
PMID- 29341129
TI - Diagnosing Crime and Diagnosing Disease-II: Visual Pattern Perception and
Diagnostic Accuracy.
AB - Previously, we reviewed how general cognitive processes might be susceptible to
bias across both forensic and clinical fields, and how interdisciplinary
comparisons could reduce error. We discuss several examples of clinical tasks
which are heavily dependent on visual processing, comparing them to eyewitness
identification (EI). We review the "constructive" nature of visual processing,
and how contextual factors influence both medical experts and witnesses in
decision making and recall. Overall, studies suggest common cognitive factors
uniting these visual tasks, in both their strengths and shortcomings. Recently
forensic sciences have advocated reducing errors by identifying and controlling
nonrelevant information. Such efforts could effectively assist medical diagnosis.
We suggest potential remedies for cognitive bias in these tasks. These can
generalize across the clinical and forensic domains, including controlling the
sequencing of contextual factors. One solution is an agnostic primary reading
before incorporation of a complete history and interpretation.
PMID- 29341131
TI - A retrospective study of feline trauma patients admitted to a referral centre.
AB - OBJECTIVE: To identify prognostic information and provide recommendations for
management of feline trauma patients. METHODS: Retrospective analysis of case
records for 185 cats presented as emergency trauma cases to a referral hospital
between February 2009 and December 2013. Each case was assigned a severity score
from 1 (very minor injuries) to 6 (moribund, dying). The data were analysed using
Mann-Whitney U and Spearman's rank correlation tests. Logistic regression was
used to calculate odds ratios. RESULTS: Out of 185 cats, 22 (11%) did not survive
to discharge. Those presenting with a higher severity score had a higher rate of
mortality and a longer period of hospitalisation. Road traffic accidents were the
most common cause of trauma (104/185) and had the highest mortality and
complication rates. Cats with circulatory shock and multiple injuries were
identified as having a higher rate of mortality. CLINICAL SIGNIFICANCE: Cats
involved in road traffic accidents and that present with signs of shock or
multiple injuries following a traumatic event have an increased mortality rate.
Cats with a higher severity score had an increased duration of hospitalisation.
PMID- 29341133
TI - Development and initial validity of the in-hand manipulation assessment.
AB - BACKGROUND/AIM: A review of the literature related to in-hand manipulation (IHM)
revealed that there is no assessment which specifically measures this construct
in the adult population. This study reports the face and content validity of an
IHM assessment for adults with impaired hand function based on expert opinion.
METHODS: The definition of IHM skills, assessment tasks and scoring methods
identified from literature was discussed in a focus group (n = 4) to establish
face validity. An expert panel (n = 16) reviewed the content validity of the
proposed assessment; evaluating the representativeness and relevance of
encompassing the IHM skills in the proposed assessment tasks, the clarity and
importance to daily life of the task and the clarity and applicability to
clinical environment of the scoring method. The content validity was calculated
using the content validity index for both the individual task and all tasks
together (I-CVI and S-CVI). Feedback was incorporated to create the assessment.
RESULTS: The focus group members agreed to include 10 assessment tasks that
covered all IHM skills. In the expert panel review, all tasks received an I-CVI
above 0.78 and S-CVI above 0.80 in representativeness and relevance ratings,
representing good content validity. With the comments from the expert panel,
tasks were modified to improve the clarity and importance to daily life. A four
point Likert scale was identified for assessing both the completion of the
assessment tasks and the quality of IHM skills within the task performance.
CONCLUSION: Face and content validity were established in this new IHM
assessment. Further studies to examine psychometric properties and use within
clinical practice are recommended.
PMID- 29341132
TI - Acanthoic acid suppresses lipin1/2 via TLR4 and IRAK4 signalling pathways in EtOH
and lipopolysaccharide-induced hepatic lipogenesis.
AB - OBJECTIVES: In alcoholic liver disease, alcohol and lipopolysaccharide (LPS) are
major stimulation factors of hepatic lipogenesis. Our objective was to determine
the protective mechanism of acanthoic acid (AA) in EtOH- and LPS-induced hepatic
lipogenesis. METHODS: HSC-T6 cells were treated with ethanol (200 mm) plus LPS (1
MUg/ml) for 1 h, followed by AA (10 or 20 MUm) for another 6 h. C57BL/6 mice were
pretreated with of AA (20 and 40 mg/kg) or equal volume of saline and then
exposed to three doses of ethanol (5 g/kg body weight) within 24 h. The mice were
sacrificed at 6 h after the last ethanol dosing. KEY FINDINGS: Acanthoic acid
significantly decreased the expressions of alpha-SMA, collagen-I, SREBP-1, and
lipin1/2 induced, also decreased fat droplets caused by EtOH/LPS. AA treatment
decreased the protein expressions of TLR4, CD14, IRAK4, TRAF3, p-TAK1 and NF
kappaB increased by EtOH/LPS on HSC cells. Results in vivo were consistent with
results in vitro. CONCLUSIONS: Our data demonstrated that AA might modulate
hepatic fibrosis and lipid deposition in HSC-T6 cell stimulated with ethanol
combined with LPS by decreasing lipin1/2 via TLR4 and IRAK4 signalling pathways,
and AA might be considered as a potential therapeutic candidate for alcoholic
liver disease.
PMID- 29341134
TI - Fatal Hemorrhage from an Arteriovenous Fistula.
AB - In this study, we present two cases of sudden deaths of people with end-stage
kidney with arteriovenous fistulas for long-term hemodialysis treatment. This
procedure is associated with a number of known complications. While stenosis,
thrombosis, and infection are well known, lethal hemorrhage from arteriovenous
fistula is much less commonly encountered. Inspection of the bodies at the scene
of the death by a medical examiner suggested that the deaths were due to
exsanguination. Autopsies revealed visible defects on the front wall of the
arteriovenous fistulas. Microscopic examination showed wall necrosis with
infiltration of various inflammatory cells. Deaths were due to exsanguination
from the ulcerated arteriovenous fistulas in patients with chronic renal failure.
Further investigation revealed that complications in the area around the
arteriovenous fistulas were known and were being treated until a sudden rupture
of the vessels and hemorrhage from the arteriovenous fistulas resulted in the
deaths.
PMID- 29341130
TI - Mitochondrial function and autophagy: integrating proteotoxic, redox, and
metabolic stress in Parkinson's disease.
AB - Parkinson's disease (PD) is a movement disorder with widespread neurodegeneration
in the brain. Significant oxidative, reductive, metabolic, and proteotoxic
alterations have been observed in PD postmortem brains. The alterations of
mitochondrial function resulting in decreased bioenergetic health is important
and needs to be further examined to help develop biomarkers for PD severity and
prognosis. It is now becoming clear that multiple hits on metabolic and signaling
pathways are likely to exacerbate PD pathogenesis. Indeed, data obtained from
genetic and genome association studies have implicated interactive contributions
of genes controlling protein quality control and metabolism. For example, loss of
key proteins that are responsible for clearance of dysfunctional mitochondria
through a process called mitophagy has been found to cause PD, and a significant
proportion of genes associated with PD encode proteins involved in the autophagy
lysosomal pathway. In this review, we highlight the evidence for the targeting of
mitochondria by proteotoxic, redox and metabolic stress, and the role autophagic
surveillance in maintenance of mitochondrial quality. Furthermore, we summarize
the role of alpha-synuclein, leucine-rich repeat kinase 2, and tau in modulating
mitochondrial function and autophagy. Among the stressors that can overwhelm the
mitochondrial quality control mechanisms, we will discuss 4-hydroxynonenal and
nitric oxide. The impact of autophagy is context depend and as such can have both
beneficial and detrimental effects. Furthermore, we highlight the potential of
targeting mitochondria and autophagic function as an integrated therapeutic
strategy and the emerging contribution of the microbiome to PD susceptibility.
PMID- 29341136
TI - Phylogeny and distribution of protein kinase C variants in the zebrafish.
AB - Conventional protein kinases-consisting of alpha, beta, and gamma family members
play key roles in numerous signal transduction events. Phylogenetic analysis
demonstrated the existence of five prkcs (the genes representing PKCs) in
zebrafish, two paralogous forms of prkca and prkcb and one prkcg variant. mRNA
expression analysis showed distinct, mainly nervous system specific expression,
for all five prkc genes. For prkca and prkcb paralogs prominent expression can be
seen in the telencephalon, in diencephalic regions such as the habenula or the
optic tectum, in hypothalamic areas and in distinct cerebellar structures. Each
transcript is additionally expressed in distinct areas: prkcaa is highly abundant
in cranial sensory ganglia and in dorsal neurons of the hindbrain and the spinal
cord, prkcab is strongly expressed in additional cerebellar regions, prkcba shows
expression in the pectoral fin, the otic vesicle and in the proximal convoluted
tubule of the kidney, and prkcbb shows prominent expression in different
hypothalamic areas. Expression of prkcg is most striking in the cerebellum. As
zebrafish PKCs are expressed in structures that are equivalent to mammals, the
zebrafish model is well suited to study evolutionary conserved functions of PKCs
in development and disease.
PMID- 29341135
TI - Phenolic fractions from nine Trifolium species modulate the coagulant properties
of blood plasma in vitro without cytotoxicity towards blood cells.
AB - OBJECTIVE: The study covers an evaluation of the influence of extracts (1-50
MUg/ml), isolated from aerial parts of nine Trifolium L. species (i.e. T.
alexandrinum, T. fragiferum, T. hybridum, T. incarnatum, T. pallidum, T.
pratense, T. resupinatum var. majus, T. resupinatum var. resupinatum and T.
scabrum) on haemostatic properties of blood plasma. METHODS: The clot formation
and fibrinolysis assay (CFF), blood clotting times, the extrinsic and intrinsic
coagulation pathway-dependent polymerization of plasma fibrin were measured. The
effects of plant extracts on amidolytic activity of thrombin were also evaluated
and compared with argatroban, an antithrombotic drug. Cytotoxicity was assessed
in a model of blood platelets and as the viability of peripheral blood
mononuclear cells. KEY FINDINGS: While no changes in blood clotting times or
fibrinolytic properties of blood plasma were found, some fractions impaired the
blood plasma coagulation induced by the intrinsic coagulation pathway. Reduction
in the maximal velocity of fibrin polymerization was also observed in the clot
formation and fibrinolysis assay. No cytotoxicity of Trifolium extracts towards
the investigated cells was recorded. CONCLUSIONS: The most efficient
anticoagulant activity in plasma was found for T. fragiferum and T. incarnatum
extracts, while the T. alexandrinum fraction was the most effective inhibitor of
thrombin amidolytic activity.
PMID- 29341137
TI - Estimation of Chronological Age from Postmortem Tissues Based on Amino Acid
Racemization.
AB - Skin and cartilage tissue specimens from 32 male and 13 female corpses aged
between 17 and 50 years were collected within 24 h after the death. Each specimen
was analyzed for the composition of dextro (D) and levo (L) forms of aspartate,
glutamate, and alanine. Linear regression models were constructed using ln [(1 +
D/L)/(1 - D/L] equation to define the relationship between the extent of
racemization and the chronological age. Aspartate D/L rates from cartilage showed
high correlation (r = 0.779, p < 0.001, n = 45). Aspartate D/L rates from skin
showed very low correlation (r = 0.356, p < 0.002, n = 44). The multilinear
regression model of both aspartate D/L rates of cartilage and skin tissues in 44
cases yielded a coefficient of r = 0.828 (p < 0.001). In conclusion, only
racemization rate of Aspartate both in the skin and the cartilage tissues
correlated with the chronological age. Our results may imply that the age can be
estimated more precisely if two different tissue specimens are obtained from one
corpse.
PMID- 29341138
TI - Model fitting for small skin permeability data sets: hyperparameter optimisation
in Gaussian Process Regression.
AB - OBJECTIVES: The aim of this study was to investigate how to improve predictions
from Gaussian Process models by optimising the model hyperparameters. METHODS:
Optimisation methods, including Grid Search, Conjugate Gradient, Random Search,
Evolutionary Algorithm and Hyper-prior, were evaluated and applied to previously
published data. Data sets were also altered in a structured manner to reduce
their size, which retained the range, or 'chemical space' of the key descriptors
to assess the effect of the data range on model quality. KEY FINDINGS: The Hyper
prior Smoothbox kernel results in the best models for the majority of data sets,
and they exhibited significantly better performance than benchmark quantitative
structure-permeability relationship (QSPR) models. When the data sets were
systematically reduced in size, the different optimisation methods generally
retained their statistical quality, whereas benchmark QSPR models performed
poorly. CONCLUSIONS: The design of the data set, and possibly also the approach
to validation of the model, is critical in the development of improved models.
The size of the data set, if carefully controlled, was not generally a
significant factor for these models and that models of excellent statistical
quality could be produced from substantially smaller data sets.
PMID- 29341139
TI - Exploitation of the Ultraviolet Properties and Machine Cut Edges of Paper to
Associate and Sequence Sheets in a Ream.
AB - Previously unreported line patterns visible under ultraviolet light were observed
on a proportion of plain white A4 printer/copier paper from different
manufacturers. These Ultraviolet Line Patterns (UVLPs) usually appear as stripes
down the vertical length of the paper. Typically, the UVLPs were found to
"repeat" through the ream in a predictable way, while also changing. It is
postulated that the repeating nature of the UVLPs is a result of the way that
paper is manufactured. This leads to the ability to sequence the sheets compared
to their original source paper. Even in the absence of UVLPs, it is possible to
use our observation of the manufacturing process to anticipate the order of
several sheets of paper and conclusively associate them, in some cases, by
physically fitting their machine cut edges and crossing paper fibers. Such a
novel approach to examining questioned documents would be highly useful in
forensic casework.
PMID- 29341140
TI - Lipoprotein modifications by gingipains of Porphyromonas gingivalis.
AB - BACKGROUND AND OBJECTIVE: Several studies have shown an association between
periodontitis and cardiovascular disease (CVD). Atherosclerosis is the major
cause of CVD, and a key event in the development of atherosclerosis is
accumulation of lipoproteins within the arterial wall. Bacteria are the primary
etiologic agents in periodontitis and Porphyromonas gingivalis is the major
pathogen in the disease. Several studies support a role of modified low-density
lipoprotein (LDL) in atherogenesis; however, the pathogenic stimuli that induce
the changes and the mechanisms by which this occur are unknown. This study aims
to identify alterations in plasma lipoproteins induced by the periodontopathic
species of bacterium, P. gingivalis, in vitro. MATERIAL AND METHODS: Plasma
lipoproteins were isolated from whole blood treated with wild-type and gingipain
mutant (lacking either the Rgp- or Kgp gingipains) P. gingivalis by
density/gradient-ultracentrifugation and were studied using 2-dimensional gel
electrophoresis followed by matrix-assisted laser desorption/ionization mass
spectrometry. Porphyromonas gingivalis-induced lipid peroxidation and antioxidant
levels were measured by thiobarbituric acid-reactive substances and antioxidant
assay kits, respectively, and lumiaggregometry was used for measurement of
reactive oxygen species (ROS) and aggregation. RESULTS: Porphyromonas gingivalis
exerted substantial proteolytic effects on the lipoproteins. The Rgp gingipains
were responsible for producing 2 apoE fragments, as well as 2 apoB-100 fragments,
in LDL, and the Kgp gingipain produced an unidentified fragment in high-density
lipoproteins. Porphyromonas gingivalis and its different gingipain variants
induced ROS and consumed antioxidants. Both the Rgp and Kgp gingipains were
involved in inducing lipid peroxidation. CONCLUSION: Porphyromonas gingivalis has
the potential to change the expression of lipoproteins in blood, which may
represent a crucial link between periodontitis and CVD.
PMID- 29341141
TI - Dual Effects of Creatinine on the Formation of 2-Amino-1-Methyl-6-Phenylimidazo
[4,5-b]pyridine (PhIP).
AB - : Creatinine was found to not only act as a precursor of 2-amino-1-methyl-6
phenylimidazo [4,5-b]pyridine (PhIP) formation but also inhibit PhIP formation in
a creatinine/phenylalanine model system. The dual mechanistic effects of
creatinine on PhIP formation were then investigated in a model system. Adducts of
creatinine-PhIP were detected by quadrupole-time-of-flight mass spectrometry and
were found to be a likely explanation for the substantial decrease in the yield
of PhIP when excess creatinine was supplied. Structures of probable adducts were
predicted in molecular docking studies, which showed that hydrogen bonds were
formed between creatinine and PhIP in 1:1 and 2:1 ratios. Furthermore, the active
sites during creatinine-PhIP adduct formation (the primary amino groups [N2 -]
and sp2 nitrogen atoms [N3 ] of creatinine and PhIP) match the active sites of
PhIP metabolism and adducts of PhIP/lipid-derived reactive carbonyls. This
verifies that creatinine inhibits PhIP production via the formation of adducts
with hydrogen bonds at the N2 and N3 sites. PRACTICAL APPLICATION: This study
enhances the understanding of how creatinine affects PhIP formation, reveals a
new PhIP inhibition mechanism, and will be useful for developing technology to
control PhIP formation during food processing.
PMID- 29341142
TI - Evolutionary and genetic features of drug targets.
AB - In the modern drug discovery pipeline, identification of novel drug targets is a
critical step. Despite rapid progress in developing biomedical techniques, it is
still a great challenge to find promising new targets from the ample space of
human genes. This fact is partially responsible for the situation of "more
investments, fewer drugs" in the pharmaceutical industry. A series of recent
researches revealed that successfully targeted genes share some common
evolutionary and genetic features, which means that the knowledge accumulated in
modern evolutionary biology and genetics is very helpful to identify potential
drug targets and to find new drugs as well. In this article, we comprehensively
summarize the links between human drug targets and genetic diseases and their
evolutionary origins, with an attempt to introduce these novel concepts and their
medical implications to the biomedical community.
PMID- 29341143
TI - Loss of alkaline ceramidase inhibits autophagy in Arabidopsis and plays an
important role during environmental stress response.
AB - Sphingolipids, a class of bioactive lipids found in cell membranes, can modulate
the biophysical properties of the membranes and play a critical role in signal
transduction. Sphingolipids are involved in autophagy in humans and yeast, but
their role in autophagy in plants is not well understood. In this study, we
reported that the AtACER, an alkaline ceramidase that hydrolyses ceramide to long
chain base (LCB), functions in autophagy process in Arabidopsis. Our empirical
data showed that the loss of AtACER inhibited autophagy, and its overexpression
promoted autophagy under nutrient, salinity, and oxidative stresses.
Interestingly, nitrogen deprivation significantly affected the sphingolipid's
profile in Arabidopsis thaliana, especially the LCBs. Furthermore, the exogenous
application of LCBs also induced autophagy. Our findings revealed a novel
function of AtACER, where it was found to involve in the autophagy process, thus,
playing a crucial role in the maintenance of a dynamic loop between sphingolipids
and autophagy for cellular homeostasis under various environmental stresses.
PMID- 29341144
TI - Role of micro-RNAs in breast cancer surgery.
AB - BACKGROUND: The management of breast cancer has changed dramatically in the
molecular era. Micro-RNAs can contribute to multiple facets of cancer surgery.
METHODS: This narrative review, based on years of research on the role of micro
RNAs, focused on the potential of these small, robust RNAs to influence all
aspects of breast cancer surgery. RESULTS: Micro-RNAs have a potential role as
biomarkers in the diagnosis, prognosis and evaluation of response to therapy in
breast cancer. They may also contribute to future therapeutic strategies.
CONCLUSION: The molecular era has changed understanding of cancer. Micro-RNAs
have the potential for use in personalized cancer strategies.
PMID- 29341145
TI - Cancer surgery in the genomic era.
PMID- 29341146
TI - Defining the molecular pathology of pancreatic body and tail adenocarcinoma.
AB - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a dismal disease,
with very little improvement in survival over the past 50 years. Recent large
scale genomic studies have improved understanding of the genomic and
transcriptomic landscape of the disease, yet very little is known about molecular
heterogeneity according to tumour location in the pancreas; body and tail PDACs
especially tend to have a significantly worse prognosis. The aim was to
investigate the molecular differences between PDAC of the head and those of the
body and tail of the pancreas. METHODS: Detailed correlative analysis of
clinicopathological variables, including tumour location, genomic and
transcriptomic data, was performed using the Australian Pancreatic Cancer Genome
Initiative (APGI) cohort, part of the International Cancer Genome Consortium
study. RESULTS: Clinicopathological data were available for 518 patients
recruited to the APGI, of whom 421 underwent genomic analyses; 179 of these
patients underwent whole-genome and 96 RNA sequencing. Patients with tumours of
the body and tail had significantly worse survival than those with pancreatic
head tumours (12.1 versus 22.0 months; P = 0.001). Location in the body and tail
was associated with the squamous subtype of PDAC. Body and tail PDACs enriched
for gene programmes involved in tumour invasion and epithelial-to-mesenchymal
transition, as well as features of poor antitumour immune response. Whether this
is due to a molecular predisposition from the outset, or reflects a later time
point on the tumour molecular clock, requires further investigation using well
designed prospective studies in pancreatic cancer. CONCLUSION: PDACs of the body
and tail demonstrate aggressive tumour biology that may explain worse clinical
outcomes.
PMID- 29341147
TI - Genotype and risk of tumour rupture in gastrointestinal stromal tumour.
AB - BACKGROUND: Tumour rupture is a strong predictor of poor outcome in
gastrointestinal stromal tumours (GISTs) of the stomach and small intestine. The
objective was to determine whether tumour genotype was associated with risk of
rupture. METHODS: Rupture was classified according to the definition proposed by
the Oslo Sarcoma Group. Since January 2000, data were registered retrospectively
for all patients at Oslo University Hospital undergoing surgery for localized
GIST of the stomach or small intestine. Tumour genotype was analysed by Sanger
sequencing. RESULTS: Two hundred and nine patients with mutation data available
were identified. Tumour rupture occurred in 37 patients. Among the 155 patients
with KIT exon 11 mutations, an increased risk of rupture was observed with a
deletion or insertion-deletion (25 of 86, 29 per cent) compared with
substitutions (5 of 50, 10 per cent) or duplications/insertions (2 of 19, 11 per
cent) (P = 0.014). Notably, rupture occurred in 17 of 46 tumours (37 per cent)
with deletions involving codons 557 and 558 (del557/558) versus 15 of 109 (13.8
per cent) with other exon 11 mutations (P = 0.002). This association was confined
to gastric tumours: 12 of 34 (35 per cent) with del557/558 ruptured versus six of
77 (8 per cent) with other exon 11 mutations (P = 0.001). In multivariable
logistic regression analysis, del557/558 and tumour size were associated with an
increased likelihood of tumour rupture, but mitotic count was not. CONCLUSION:
Gastric GISTs with KIT exon 11 deletions involving codons 557 and 558 are at
increased risk of tumour rupture. This high-risk feature can be identified in the
diagnostic evaluation and should be included in the assessment when neoadjuvant
imatinib treatment is considered.
PMID- 29341148
TI - Outcomes after prophylactic gastrectomy for hereditary diffuse gastric cancer.
AB - BACKGROUND: Patients with hereditary diffuse gastric cancer and a CDH1 mutation
have a 60-80 per cent lifetime risk of developing diffuse gastric cancer. Total
prophylactic gastrectomy eliminates this risk, but is associated with
considerable morbidity. The effectiveness (removal of all gastric mucosa) and
outcomes of this procedure were evaluated retrospectively. METHODS: All
consecutive individuals undergoing a prophylactic gastrectomy for a CDH1 mutation
or gastric signet ring cell foci at the authors' institute between 2005 and 2017
were included. RESULTS: In 25 of 26 patients, intraoperative frozen-section
examination (proximal resection margin) was used to verify complete removal of
gastric mucosa. All definitive resection margins were free of gastric mucosa, but
only after the proximal margin had been reresected in nine patients. In the first
year after surgery, five of the 26 patients underwent a relaparotomy for
adhesiolysis (2 patients) or jejunostomy-related complications (3 patients). Six
patients were readmitted to the hospital within 1 year for nutritional and/or
psychosocial support (4 patients) or surgical reintervention (2 patients). Mean
weight loss after 1 year was 15 (95 per cent c.i. 12 to 18) per cent. For the 25
patients with a follow-up at 1 year or more, functional complaints were reported
more frequently at 1 year than at 3 months after the operation: bile reflux (15
versus 11 patients respectively) and dumping (11 versus 7 patients). The majority
of patients who worked or studied before surgery (15 of 19) had returned fully to
these activities within 1 year. CONCLUSION: The considerable morbidity and
functional consequences of gastrectomy should be considered when counselling
individuals with an inherited predisposition to diffuse gastric cancer.
Intraoperative frozen-section examination is recommended to remove all risk
bearing gastric mucosa.
PMID- 29341149
TI - Quality-of-life implications of risk-reducing cancer surgery.
AB - BACKGROUND: Modern advances in genetic sequencing techniques have allowed for
increased availability of genetic testing for hereditary cancer syndromes.
Consequently, more people are being identified as mutation carriers and becoming
aware of their increased risk of malignancy. Testing is commonplace for many
inheritable cancer syndromes, and with that comes the knowledge of being a gene
carrier for some patients. With increased risk of malignancy, many guidelines
recommend that gene carriers partake in risk reduction strategies, including risk
reducing surgery for some syndromes. This review explores the quality-of-life
consequences of genetic testing and risk-reducing surgery. METHODS: A narrative
review of PubMed/MEDLINE was performed, focusing on the health-related quality-of
life implications of surgery for hereditary breast and ovarian cancer, familial
adenomatous polyposis and hereditary diffuse gastric cancer. RESULTS: Risk
reducing surgery almost uniformly decreases cancer anxiety and affects patients'
quality of life. CONCLUSION: Although the overwhelming quality-of-life
implications of surgery are neutral to positive, risk-reducing surgery is
irreversible and can be associated with short- and long-term side-effects.
PMID- 29341150
TI - Effect of Akt activation and experimental pharmacological inhibition on responses
to neoadjuvant chemoradiotherapy in rectal cancer.
AB - BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) is one of the preferred initial
treatment strategies for locally advanced rectal cancer. Responses are variable,
and most patients still require surgery. The aim of this study was to identify
molecular mechanisms determining poor response to CRT. METHODS: Global gene
expression and pathway enrichment were assessed in pretreatment biopsies from
patients with non-metastatic cT2-4 N0-2 rectal cancer within 7 cm of the anal
verge. Downstream Akt activation was assessed in an independent set of
pretreatment biopsies and in colorectal cancer cell lines using
immunohistochemistry and western blot respectively. The radiosensitizing effects
of the Akt inhibitor MK2206 were assessed using clonogenic assays and xenografts
in immunodeficient mice. RESULTS: A total of 350 differentially expressed genes
were identified, of which 123 were upregulated and 199 downregulated in tumours
from poor responders. Mitochondrial oxidative phosphorylation (P < 0.001) and
phosphatidylinositol signalling pathways (P < 0.050) were identified as
significantly enriched pathways among the set of differentially expressed genes.
Deregulation of both pathways is known to result in Akt activation, and high
immunoexpression of phosphorylated Akt S473 was observed among patients with a
poor histological response (tumour regression grade 0-2) to CRT (75 per cent
versus 48 per cent in those with a good or complete response; P = 0.016). Akt
activation was also confirmed in the radioresistant cell line SW480, and a 50 per
cent improvement in sensitivity to CRT was observed in vitro and in vivo when
SW480 cells were exposed to the Akt inhibitor MK2206 in combination with
radiation and 5-fluorouracil. CONCLUSION: Akt activation is a key event in the
response to CRT. Pharmacological inhibition of Akt activation may enhance the
effects of CRT. Surgical relevance Organ preservation is an attractive
alternative in rectal cancer management following neoadjuvant chemoradiotherapy
(CRT) to avoid the morbidity of radical surgery. Molecular steps associated with
tumour response to CRT may provide a useful tool for the identification of
patients who are candidates for no immediate surgery. In this study, tumours
resistant to CRT were more likely to have activation of specific genetic pathways
that result in phosphorylated Akt (pAkt) activation. Pretreatment biopsy tissues
with high immunoexpression of pAkt were more likely to exhibit a poor
histological response to CRT. In addition, the introduction of a pAkt inhibitor
to cancer cell lines in vitro and in vivo led to a significant improvement in
sensitivity to CRT. Identification of pAkt-activated tumours may thus allow the
identification of poor responders to CRT. In addition, the concomitant use of
pAkt inhibitors to increase sensitivity to CRT in patients with rectal cancer may
constitute an interesting strategy for increasing the chance of a complete
response to treatment and organ preservation.
PMID- 29341152
TI - Meta-analysis of the prognostic value of CpG island methylator phenotype in
gastric cancer.
AB - BACKGROUND: CpG island methylator phenotype (CIMP) has been identified as a
distinct molecular subtype of gastric cancer, yet associations with survival are
conflicting. A meta-analysis was performed to estimate the prognostic
significance of CIMP. METHODS: Embase, MEDLINE, PubMed, PubMed Central and
Cochrane databases were searched systematically for studies related to the
association between CIMP and survival in patients undergoing potentially curative
resection for gastric cancer. RESULTS: A total of 918 patients from ten studies
were included, and the median proportion of tumours with CIMP-high (CIMP-H)
status was 40.9 (range 4.8-63) per cent. Gene panels for assessing CIMP status
varied between the studies. Pooled analysis suggested that specimens exhibiting
CIMP-H were associated with poorer 5-year survival (odds ratio (OR) for death
1.48, 95 per cent c.i. 1.10 to 1.99; P = 0.009). Significant heterogeneity was
observed between studies (I2 = 88 per cent, P < 0.001). Subgroup analysis
according to whether studies showed a tendency towards poor (5 studies) or
improved (5) outcomes for patients with CIMP-H tumours, revealed that CIMP-H was
associated with both poor (OR for death 8.15, 4.65 to 14.28, P < 0.001;
heterogeneity I2 = 52 per cent, P = 0.08) and improved (OR 0.42, 0.27 to 0.65; P
< 0.001, heterogeneity I2 = 0 per cent, P = 0.960) survival. CONCLUSION: There
was heterogeneity in the gene panels used to identify CIMP, which may explain the
survival differences.
PMID- 29341153
TI - Circulating tumour cells and DNA as liquid biopsies in gastrointestinal cancer.
AB - BACKGROUND: Blood is the most extensively studied body fluid and, because it
contains circulating tumour cells (CTCs) and circulating tumour-derived cell-free
DNA (ctDNA), it may represent a liquid biopsy for cancer. Methods for enrichment
and detection of CTCs and ctDNA, their clinical applications and future
opportunities in gastrointestinal cancers were the focus of this review. METHODS:
The PubMed database was searched for literature up to 24 June 2017, with a focus
on the past 10 years. Identified articles were further scrutinized for relevant
references. Articles were those in English relating to colorectal, gastric and
pancreatic cancer. RESULTS: Both CTCs and ctDNA are in low abundance compared
with other cellular components of blood, but effective enrichment and highly
sensitive techniques are available for their detection. Potential clinical
applications of these liquid biopsies include screening, prognostic
stratification, therapy administration, monitoring of treatment effect or
resistance, and surveillance. Liquid biopsies provide opportunities to reduce the
need for invasive tissue sampling, especially in the context of intratumoral
heterogeneity and the need for tumour genotyping. CONCLUSION: Liquid biopsies
have applications in gastrointestinal cancers to improve clinical decision
making.
PMID- 29341151
TI - Gut microbiome influences on anastomotic leak and recurrence rates following
colorectal cancer surgery.
AB - BACKGROUND: The pathogenesis of colorectal cancer recurrence after a curative
resection remains poorly understood. A yet-to-be accounted for variable is the
composition and function of the microbiome adjacent to the tumour and its
influence on the margins of resection following surgery. METHODS: PubMed was
searched for historical as well as current manuscripts dated between 1970 and
2017 using the following keywords: 'colorectal cancer recurrence', 'microbiome',
'anastomotic leak', 'anastomotic failure' and 'mechanical bowel preparation'.
RESULTS: There is a substantial and growing body of literature to demonstrate the
various mechanisms by which environmental factors act on the microbiome to alter
its composition and function with the net result of adversely affecting
oncological outcomes following surgery. Some of these environmental factors
include diet, antibiotic use, the methods used to prepare the colon for surgery
and the physiological stress of the operation itself. CONCLUSION: Interrogating
the intestinal microbiome using next-generation sequencing technology has the
potential to influence cancer outcomes following colonic resection.
PMID- 29341154
TI - Emerging methods in colorectal cancer screening.
PMID- 29341155
TI - Long-term outcome of prophylactic thyroidectomy in children carrying RET germline
mutations.
AB - BACKGROUND: A comprehensive assessment has not been undertaken of long-term
outcomes in children carrying germline RET mutations and undergoing prophylactic
thyroidectomy with the aim of preventing medullary thyroid cancer (MTC). METHODS:
A retrospective outcome study (1994-2017) of prophylactic thyroidectomy in
children, with and without central node dissection, was performed at a tertiary
surgical centre. RESULTS: Some 167 children underwent prophylactic thyroidectomy,
109 without and 58 with concomitant central node dissection. In the highest-risk
mutational category, MTC was found in five of six children (83 per cent) aged 3
years or less. In the high-risk category, MTC was present in six of 20 children
(30 per cent) aged 3 years or less, 16 of 36 (44 per cent) aged 4-6 years, and 11
of 16 (69 per cent) aged 7-12 years (P = 0.081). In the moderate-risk category,
MTC was seen in one of nine children (11 per cent) aged 3 years or less, one of
26 (4 per cent) aged 4-6 years, three of 26 (12 per cent) aged 7-12 years, and
seven of 16 (44 per cent) aged 13-18 years (P = 0.006). Postoperative
hypoparathyroidism was more frequent in older children (32 per cent in the oldest
age group versus 3 per cent in the youngest; P = 0.002), whether or not central
node dissection was carried out. Three children developed recurrent laryngeal
nerve palsy; all had undergone central node dissection (P = 0.040). All
complications resolved within 6 months. Postoperative normalization of calcitonin
serum levels was achieved in 114 (99.1 per cent) of 115 children with raised
preoperative values. No residual structural disease or recurrence was observed.
CONCLUSION: Early prophylactic thyroidectomy is a viable surgical concept in
experienced hands, sparing older children the postoperative morbidity associated
with delayed neck surgery.
PMID- 29341156
TI - Introducing genomics into cancer care.
PMID- 29341159
TI - Clinicopathological, genomic and immunological factors in colorectal cancer
prognosis.
AB - BACKGROUND: Numerous factors affect the prognosis of colorectal cancer (CRC),
many of which have long been identified, such as patient demographics and the
multidisciplinary team. In more recent years, molecular and immunological
biomarkers have been shown to have a significant influence on patient outcomes.
Whilst some of these biomarkers still require ongoing validation, if proven to be
worthwhile they may change our understanding and future management of CRC. The
aim of this review was to identify the key prognosticators of CRC, including new
molecular and immunological biomarkers, and outline how these might fit into the
whole wider context for patients. METHODS: Relevant references were identified
through keyword searches of PubMed and Embase Ovid SP databases. RESULTS: In
recent years there have been numerous studies outlining molecular markers of
prognosis in CRC. In particular, the Immunoscore(r) has been shown to hold strong
prognostic value. Other molecular biomarkers are useful in guiding treatment
decisions, such as mutation testing of genes in the epidermal growth factor
receptor pathway. However, epidemiological studies continue to show that patient
demographics are fundamental in predicting outcomes. CONCLUSION: Current
strategies for managing CRC are strongly dependent on clinicopathological
staging, although molecular testing is increasingly being implemented into
routine clinical practice. As immunological biomarkers are further validated,
their testing may also become routine. To obtain clinically useful information
from new biomarkers, it is important to implement them into a model that includes
all underlying fundamental factors, as this will enable the best possible
outcomes and deliver true precision medicine.
PMID- 29341157
TI - Minimizing inequality in access to precision medicine in breast cancer by real
time population-based molecular analysis in the SCAN-B initiative.
AB - BACKGROUND: Selection of systemic therapy for primary breast cancer is currently
based on clinical biomarkers along with stage. Novel genomic tests are
continuously being introduced as more precise tools for guidance of therapy,
although they are often developed for specific patient subgroups. The Sweden
Cancerome Analysis Network - Breast (SCAN-B) initiative aims to include all
patients with breast cancer for tumour genomic analysis, and to deliver molecular
subtype and mutational data back to the treating physician. METHODS: An
infrastructure for collection of blood and fresh tumour tissue from all patients
newly diagnosed with breast cancer was set up in 2010, initially including seven
hospitals within the southern Sweden regional catchment area, which has 1.8
million inhabitants. Inclusion of patients was implemented into routine clinical
care, with collection of tumour tissue at local pathology departments for
transport to the central laboratory, where routines for rapid sample processing,
RNA sequencing and biomarker reporting were developed. RESULTS: More than 10 000
patients from nine hospitals have currently consented to inclusion in SCAN-B with
high (90 per cent) inclusion rates from both university and secondary hospitals.
Tumour samples and successful RNA sequencing are being obtained from more than 70
per cent of patients, showing excellent representation compared with the national
quality registry as a truly population-based cohort. Molecular biomarker reports
can be delivered to multidisciplinary conferences within 1 week. CONCLUSION:
Population-based collection of fresh tumour tissue is feasible given a decisive
joint effort between academia and collaborative healthcare groups, and with
governmental support. An infrastructure for genomic analysis and prompt data
output paves the way for novel systemic therapy for patients from all hospitals,
irrespective of size and location.
PMID- 29341160
TI - Genetic analysis of surgical margins in oral cavity cancer.
AB - BACKGROUND: A histological, tumour-free surgical margin does not guarantee
recurrence-free survival in patients with cancer. This study investigated the
association between microsatellite alteration in tumour-free surgical margins and
local recurrence in patients with oral cavity squamous cell carcinoma. METHODS:
Patients with histologically confirmed oral cavity squamous cell carcinoma were
enrolled in this prospective study. Cancerous specimens, corresponding surgical
margins and peripheral blood were obtained. Microsatellite alteration was
investigated using six dinucleotide microsatellite markers. All samples were
amplified by PCR, followed by automatic fragment analysis. RESULTS:
Microsatellite alteration was identified in 100 specimens (69.0 per cent) from
145 patients. Among them, 85 specimens carried loss of heterozygosity, whereas 55
had microsatellite instability (MSI). Patients with MSI at the surgical margin
had a higher risk of local recurrence on multivariable analysis (odds ratio 7.17,
95 per cent c.i. 3.49 to 14.73). CONCLUSION: Molecular assessment of surgical
margins can help identify patients at risk of local recurrence.
PMID- 29341161
TI - Modalities for image- and molecular-guided cancer surgery.
AB - BACKGROUND: Surgery is the cornerstone of treatment for many solid tumours. A
wide variety of imaging modalities are available before surgery for staging,
although surgeons still rely primarily on visual and haptic cues in the operating
environment. Image and molecular guidance might improve the adequacy of resection
through enhanced tumour definition and detection of aberrant deposits.
Intraoperative modalities available for image- and molecular-guided cancer
surgery are reviewed here. METHODS: Intraoperative cancer detection techniques
were identified through a systematic literature search, with selection of peer
reviewed publications from January 2012 to January 2017. Modalities were
reviewed, described and compared according to 25 predefined characteristics. To
summarize the data in a comparable way, a three-point rating scale was applied to
quantitative characteristics. RESULTS: The search identified ten image- and
molecular-guided surgery techniques, which can be divided into four groups:
conventional, optical, nuclear and endogenous reflectance modalities.
Conventional techniques are the most well known imaging modalities, but
unfortunately have the drawback of a defined resolution and long acquisition
time. Optical imaging is a real-time modality; however, the penetration depth is
limited. Nuclear modalities have excellent penetration depth, but their
intraoperative use is limited by the use of radioactivity. Endogenous reflectance
modalities provide high resolution, although with a narrow field of view.
CONCLUSION: Each modality has its strengths and weaknesses; no single technique
will be suitable for all surgical procedures. Strict selection of modalities per
cancer type and surgical requirements is required as well as combining techniques
to find the optimal balance.
PMID- 29341162
TI - Impact of genomics on the surgical management of melanoma.
AB - BACKGROUND: Although surgery for early-stage melanoma offers the best chance of
cure, recent advances in molecular medicine have revolutionized the management of
late-stage melanoma, leading to significant improvements in clinical outcomes.
Research into the genomic drivers of disease and cancer immunology has not only
ushered in a new era of targeted and immune-based therapies for patients with
metastatic melanoma, but has also provided new tools for monitoring disease
recurrence and selecting therapeutic strategies. These advances present new
opportunities and challenges to the surgeon treating patients with melanoma.
METHODS: The literature was reviewed to evaluate diagnostic and therapeutic
advances in the management of cutaneous melanoma, and to highlight the impact of
these advances on surgical decision-making. RESULTS: Genomic testing is not
required in the surgical management of primary melanoma, although it can provide
useful information in some situations. Circulating nucleic acids from melanoma
cells can be detected in peripheral blood to predict disease recurrence before it
manifests clinically, but validation is required before routine clinical
application. BRAF mutation testing is the standard of care for all patients with
advanced disease to guide therapy, including the planning of surgery in adjuvant
and neoadjuvant settings. CONCLUSION: Surgery remains central for managing
primary melanoma, and is an important element of integrated multidisciplinary
care in advanced disease, particularly for patients with resectable metastases.
The field will undergo further change as clinical trials address the
relationships between surgery, radiotherapy and systemic therapy for patients
with high-risk, early-stage and advanced melanoma.
PMID- 29341163
TI - Extent of surgery for phaeochromocytomas in the genomic era.
AB - BACKGROUND: Germline mutations are present in 20-30 per cent of patients with
phaeochromocytoma. For patients who develop bilateral disease, complete removal
of both adrenal glands (total adrenalectomy) will result in lifelong adrenal
insufficiency with an increased risk of death from adrenal crisis.
Unilateral/bilateral adrenal-sparing surgery (subtotal adrenalectomy) offers
preservation of cortical function and independence from steroids, but leaves the
adrenal medulla in situ and thus at risk of developing new and possibly malignant
disease. Here, present knowledge about how tumour genotype relates to clinical
behaviour is reviewed, and application of this knowledge when choosing the extent
of adrenalectomy is discussed. METHODS: A literature review was undertaken of the
penetrance of the different genotypes in phaeochromocytomas, the frequency of
bilateral disease and malignancy, and the underlying pathophysiological
mechanisms, with emphasis on explaining the clinical phenotypes of
phaeochromocytomas and their associated syndromes. RESULTS: Patients with
bilateral phaeochromocytomas most often have multiple endocrine neoplasia type 2
(MEN2) or von Hippel-Lindau disease (VHL) with high-penetrance mutations for
benign disease, whereas patients with mutations in the genes encoding SDHB
(succinate dehydrogenase subunit B) or MAX (myelocytomatosis viral proto-oncogene
homologue-associated factor X) are at increased risk of malignancy. CONCLUSION:
Adrenal-sparing surgery should be the standard approach for patients who have
already been diagnosed with MEN2 or VHL when operating on the first side, whereas
complete removal of the affected adrenal gland(s) is generally recommended for
patients with SDHB or MAX germline mutations. Routine assessment of a patient's
genotype, even after the first operation, can be crucial for adopting an
appropriate strategy for follow-up and future surgery.
PMID- 29341165
TI - Histopathological and molecular classification of colorectal cancer and
corresponding peritoneal metastases.
AB - BACKGROUND: Patients with colorectal peritoneal carcinomatosis have a very poor
prognosis. The recently developed consensus molecular subtype (CMS)
classification of primary colorectal cancer categorizes tumours into four robust
subtypes, which could guide subtype-targeted therapy. CMS4, also known as the
mesenchymal subtype, has the greatest propensity to form distant metastases. CMS4
status and histopathological features of colorectal peritoneal carcinomatosis
were investigated in this study. METHODS: Fresh-frozen tissue samples from
primary colorectal cancer and paired peritoneal metastases from patients who
underwent cytoreductive surgery combined with hyperthermic intraperitoneal
chemotherapy were collected. Histopathological features were analysed, and a
reverse transcriptase-quantitative PCR test was used to assess CMS4 status of all
collected lesions. RESULTS: Colorectal peritoneal carcinomatosis was associated
with adverse histopathological characteristics, including a high percentage of
stroma in both primary tumours and metastases, and poor differentiation grade and
high-grade tumour budding in primary tumours. Furthermore, CMS4 was significantly
enriched in primary tumours with peritoneal metastases, compared with unselected
stage I-IV tumours (60 per cent (12 of 20) versus 23 per cent; P = 0.002). The
majority of peritoneal metastases (75 per cent, 21 of 28) were also classified as
CMS4. Considerable intrapatient subtype heterogeneity was observed. Notably, 15
of 16 patients with paired tumours had at least one CMS4-positive tumour
location. CONCLUSION: Significant enrichment for CMS4 was observed in colorectal
peritoneal carcinomatosis. Surgical relevance Cytoreductive surgery combined with
hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) improves survival of
selected patients with colorectal peritoneal carcinomatosis, but recurrence is
common. Histopathological and molecular analysis of colorectal peritoneal
carcinomatosis could provide clues for development of novel therapies. In this
study, colorectal peritoneal carcinomatosis was found to be enriched for tumours
with high stromal content and CMS4-positive status. To further improve prognosis
for patients with colorectal peritoneal carcinomatosis, therapies that target
tumour-stroma interaction could be added to CRS-HIPEC.
PMID- 29341167
TI - The Influence of Colloid Osmotic Pressure on Hydrostatic Pressures in High- and
Low-Flux Hemodialyzers.
AB - The aim of this study was to examine the relationship between hydrostatic trans
membrane pressure (TMPh ) and colloid osmotic pressure (COP) in low-flux (LF) and
high-flux (HF) dialyzers. Hydrostatic pressures were measured in dialyzers
distinguished by their ultrafiltration coefficient Kuf (16 and 85 mL/h/mm Hg)
under constant dialysate flow and variable blood flow (Qb ) ranging from 0 to 400
mL/min using (i) alginate (70 kDa) dissolved in dialysate, (ii) diluted,
undiluted, and concentrated plasma, or (iii) whole blood at different hematocrit,
all in absence of ultrafiltration (UF). For a given fluid, TMPh linearly
increased with increasing Qb . The intercept of the linear TMPh to Qb
relationship correlated with measured COP with an average bias of 1.00 +/- 2.26
mm Hg and a concordance correlation coefficient of 0.98. The slope of the linear
TMPh to Qb relationship increased with increasing sample viscosity and was much
larger in HF dialyzers under otherwise identical operating conditions, most
likely because of increased internal filtration. The TMPh to Qb relationship
measured in dialyzers in absence of UF can be described by the intercept related
to measured COP and the slope related to internal filtration. This relationship
could be of interest to estimate internal filtration and COP under in vivo
conditions.
PMID- 29341164
TI - Patient-derived organoid models help define personalized management of
gastrointestinal cancer.
AB - BACKGROUND: The prognosis of patients with different gastrointestinal cancers
varies widely. Despite advances in treatment strategies, such as extensive
resections and the addition of new drugs to chemotherapy regimens, conventional
treatment strategies have failed to improve survival for many tumours. Although
promising, the clinical application of molecularly guided personalized treatment
has proven to be challenging. This narrative review focuses on the
personalization of cancer therapy using patient-derived three-dimensional
'organoid' models. METHODS: A PubMed search was conducted to identify relevant
articles. An overview of the literature and published protocols is presented, and
the implications of these models for patients with cancer, surgeons and
oncologists are explained. RESULTS: Organoid culture methods have been
established for healthy and diseased tissues from oesophagus, stomach, intestine,
pancreas, bile duct and liver. Because organoids can be generated with high
efficiency and speed from fine-needle aspirations, biopsies or resection
specimens, they can serve as a personal cancer model. Personalized treatment
could become a more standard practice by using these cell cultures for extensive
molecular diagnosis and drug screening. Drug sensitivity assays can give a
clinically actionable sensitivity profile of a patient's tumour. However, the
predictive capability of organoid drug screening has not been evaluated in
prospective clinical trials. CONCLUSION: High-throughput drug screening on
organoids, combined with next-generation sequencing, proteomic analysis and other
state-of-the-art molecular diagnostic methods, can shape cancer treatment to
become more effective with fewer side-effects.
PMID- 29341168
TI - In search of a counter you can count on: relative efficacy of human visual and
automated colony counting.
AB - : To evaluate comparative efficiency of traditional vs automated colony counting
methods, cultures of Escherichia coli (ATCC 25945), Staphylococcus epidermidis
(ATCC 12225), Streptococcus pyogenes (ATCC19615) and Streptococcus pneumoniae
(ATCC49619) were prepared as pure cultures and mixed cultures at 0.5 McFarland
standard and serial dilutions were performed. Plates were inoculated in
triplicate with 50, 125, 250 and 500 colony forming units and counted by four
researchers, visually and using each of the automated counters. Colony count and
counting time were recorded. The pattern of efficiency for all bacterial species
was similar: plates with low counts were accurate and quick to count for all
methods, with an increase in time and a decrease in accuracy and precision as
counts rose. Higher counts of single round colonies required less time and had
greater precision with automated counters than human visual counting counts with
no loss of accuracy; however, counts were reduced in accuracy and increased in
time for species with less regular morphology or when plates had mixed species.
Surprisingly, a free phone application was only slightly less precise and more
time consuming than the high-end professional counter indicating that automation
may be achievable at lower cost than expected. SIGNIFICANCE AND IMPACT OF THE
STUDY: Colony quantification is essential in clinical and research settings as
well as pedagogy at the college level. Human visual (HV) counting, the most
common method, is time consuming and fraught with errors. The time, accuracy and
precision of HV counting were compared to a high-end professional automated
counter, an inexpensive phone application and a free phone application. Low cost
benefits of increased speed and accuracy with automated counting are maximized
when counting single round colonies; but much reduced if colonies have irregular
morphology or demonstrate haemolysis.
PMID- 29341169
TI - False-positive result when a diphenylcarbazide spot test is used on trivalent
chromium-passivated zinc surfaces.
AB - BACKGROUND: A colorimetric 1,5-diphenylcarbazide (DPC)-based spot test can be
used to identify hexavalent chromium on various metallic and leather surfaces.
DPC testing on trivalent chromium-passivated zinc surfaces has unexpectedly given
positive results in some cases, apparently indicating the presence of hexavalent
chromium; however, the presence of hexavalent chromium has never been confirmed
with more sensitive and accurate test methods. OBJECTIVES: To examine the
presence of hexavalent chromium on trivalent chromium-passivated zinc surfaces
with a DPC-based spot test. METHODS: A colorimetric DPC spot test was used for
the initial detection of hexavalent chromium on new and 1-year-aged trivalent
chromium-passivated zinc surfaces. Then, X-ray photoelectron spectroscopy (XPS)
was performed for all samples. RESULTS: The DPC spot test indicated the presence
of hexavalent chromium in aged, but not new, trivalent chromium passivation on
zinc; however, subsequent analysis by XPS could not confirm the presence of
chromium in a hexavalent state. CONCLUSIONS: Unintended oxidation of DPC induced
by atmospheric corrosion is suggested as a possible reason for the false-positive
reaction of the DPC test on a trivalent chromium-passivated zinc surface. Further
validation of the use of the DPC test for chromium-containing metallic surfaces
is required.
PMID- 29341172
TI - Statin use and the risk of cardiovascular implantable electronic device
infection: A cohort study in a veteran population.
AB - BACKGROUND: The rate of cardiovascular implantable electronic device infection
(CIEDI) has increased, despite the use of perioperative antibiotics at the time
of device placement or revision. This is due, in part, to the presence of
multiple comorbid conditions in an elderly population, in general, who require
CIED. Statins may have an antibacterial effect, although there is currently no
evidence that the likelihood of CIEDI has been impacted by statin use. METHODS: A
retrospective cohort study was performed to assess whether statins are associated
with a reduced risk of CIEDI. The VA Informatics and Computing Infrastructure
(VINCI) database, which includes all veterans who underwent CIED placement
between 2008 and 2015, was used. A logistic regression model was constructed to
estimate the adjusted risk of CIEDI among patients who were receiving statins
after adjusting for confounding factors. RESULTS: Overall, 18,970 CIED procedures
were included, and 98% of them were performed in men with a mean age of 71 +/- 11
years. The rate of diabetes mellitus, heart failure, advanced chronic kidney
diseases, CIEDI, positive methicillin-resistant Staphylococcus aureus nasal
colonization, and statin use were 23%, 15.7%, 3.3%, 1.14%, 12.6%, and 56%,
respectively. The logistic regression analysis showed that statins were
significantly associated with a reduced risk of CIEDI; after controlling for
other effects, the reduction was 66% (odds ratio 0.34 [0.2-0.59], P-value <
0.001). The effect of statins was confirmed by propensity score analysis.
CONCLUSIONS: Our study showed that among patients receiving statins who had
undergone CIED placement, there was a 66% reduction in subsequent CIEDI.
PMID- 29341170
TI - Identification and characterization of a new three-component nicotinic acid
hydroxylase NahAB1 B2 from Pusillimonas sp. strain T2.
AB - : Nicotinic acid (NA) is ubiquitous in nature and its microbial degradation
mechanisms are diverse. In this study, Pusillimonas sp. strain T2 was found to be
capable of utilizing NA as sole carbon and nitrogen sources. This strain could
completely degrade 300 mg l-1 NA within 3.5 h at 30 degrees C and pH 7.0 and one
of the degradation intermediate of NA was identified as 6-hydroxynicotinic acid
(6HNA). The draft genome sequences of strain T2 were determined to have a total
length of 3.3 M bp and 3054 proteins were predicted. The encoding genes of three
component NA hydroxylase (NahAB1 B2 ) genes were identified. The nahAB1 B2 genes
were heterologously expressed in the non-NA-degrading Shinella sp. strain HZN7.
The recombinant HZN7-pBBR-nahAB1 B2 converted NA into equimolar 6HNA, while the
recombinants HZN7-pBBR-nahAB1 (lacking component B2 ) and HZN7-pBBR-nahAB2
(lacking component B1 ) could not convert NA. Cell-free extracts of HZN7-pBBR
nahAB1 B2 exhibited NA hydroxylase activity. After addition of an artificial
electron acceptor (such as phenazine methosulphate, PMS), the NA hydroxylase
activity was significantly increased. The Km and Vmax values for NA were 65.94
MUmol l-1 and 260.80 +/- 5.69 mU mg-1 , respectively, using PMS as an electron
acceptor. This study provides a novel insight into the NA degradation by
bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: Nicotinic acid (NA) serves as a
model system for the degradation of N-heterocyclic aromatic compounds and the
microbial degradation mechanisms are diverse. This is the first time that a three
component hydroxylase has been identified. This study provides a novel insight
into the NA degradation by bacteria.
PMID- 29341173
TI - Strigolactones positively regulate chilling tolerance in pea and in Arabidopsis.
AB - Strigolactones (SL) fulfil important roles in plant development and stress
tolerance. Here, we characterized the role of SL in the dark chilling tolerance
of pea and Arabidopsis by analysis of mutants that are defective in either SL
synthesis or signalling. Pea mutants (rms3, rms4, and rms5) had significantly
greater shoot branching with higher leaf chlorophyll a/b ratios and carotenoid
contents than the wild type. Exposure to dark chilling significantly decreased
shoot fresh weights but increased leaf numbers in all lines. Moreover, dark
chilling treatments decreased biomass (dry weight) accumulation only in rms3 and
rms5 shoots. Unlike the wild type plants, chilling-induced inhibition of
photosynthetic carbon assimilation was observed in the rms lines and also in the
Arabidopsis max3-9, max4-1, and max2-1 mutants that are defective in SL synthesis
or signalling. When grown on agar plates, the max mutant rosettes accumulated
less biomass than the wild type. The synthetic SL, GR24, decreased leaf area in
the wild type, max3-9, and max4-1 mutants but not in max2-1 in the absence of
stress. In addition, a chilling-induced decrease in leaf area was observed in all
the lines in the presence of GR24. We conclude that SL plays an important role in
the control of dark chilling tolerance.
PMID- 29341174
TI - Sensing performance, safety, and patient acceptability of long-dipole cardiac
monitor: An innovative axillary insertion.
AB - BACKGROUND: The recommended location for implantable cardiac monitor (ICM)
insertion is the left pectoral region. We tested whether an innovative left
axillary implantation approach could be applicable for a new ICM, characterized
by a long sensing dipole. METHODS: We considered a series of 55 patients
consecutively implanted with a long-dipole ICM (BioMonitor 2); the first 30
subjects underwent prepectoral location insertion, while the subsequent 25
received the ICM in the axillary region. Sensing performances collected at 1
month follow-up were compared between the two groups. During the visit, each
patient was also asked to fill in a brief questionnaire to assess patient
acceptability of the device. RESULTS: All patients had a successful insertion of
ICM. Mean R-wave amplitude was 0.87 +/- 0.44 mV in the prepectoral group and 1.00
+/- 0.45 mV in the axillary one, without any significant difference. The
percentage of patients with visible P wave was also comparable between the two
approaches (65.5% vs 68.2%, P = 0.84). None of the patients reported device
related issues or discomfort, and ICM was generally well accepted and tolerated
by all the involved patients. CONCLUSION: Axillary insertion may represent a
valid alternative to the standard one for long-dipole ICM technology providing
not only patient acceptability but also high-quality sensing performances.
PMID- 29341175
TI - Investigation of the Axial Gap Clearance in a Hydrodynamic-Passive Magnetically
Levitated Rotary Blood Pump Using X-Ray Radiography.
AB - The HeartWare HVAD is a radial rotary blood pump with a combination of passive
magnetic and hydrodynamic bearings to levitate the impeller. The axial gap size
between impeller and housing in this bearing and its sensitivity to speed, flow,
and pressure difference is difficult to assess. Shear stresses are exceptionally
high in this tiny gap making it important for blood damage and related adverse
events. Therefore, the aim of this study was to measure the axial gap clearance
in the HVAD at different operating conditions employing radiography. To quantify
the gap size in the HVAD, the pump was positioned 30 mm in front of the X-ray
source employing a microfocus X-ray tube with an acceleration voltage up to 300
kV. Beams were detected on a flat panel detector (Perkin Elmer XRD 1611-CP3). The
pump was connected to a tubing circuit with a throttle to adjust flow (0, 5, 10
L/min) and a water glycerol mixture to set the desired viscosity (1, 4, 8 mPas).
Rotational speed was varied between 1800 and 3600 rpm. In this study, for
clinically relevant conditions at 5 L/min and 2700 rpm, the axial gap was 22 um.
The gap size increased with rotational speeds dependent on the viscosity (2.8,
6.9, and 9.4 um/1000 rpm for 1, 4, and 8 mPas, respectively), but was independent
from the volume flow and the pressure head at constant speeds. In summary, using
X-ray radiographic imaging small gaps in a rotary blood pump during operation can
be measured in a nondestructive contact-free way. The axial hydrodynamic bearing
gap in the HVAD pump was determined to be in the range of about three times the
diameter of a red blood cell. Its dependence on operating volume flow and
generated pressure head across the pump is not pronounced.
PMID- 29341176
TI - Different responses of supraventricular tachycardia with 2:1 AV block to
consecutive premature ventricular contractions.
PMID- 29341177
TI - Prevalence of antinuclear and anti-erythrocyte antibodies in healthy cats.
AB - BACKGROUND: Positive antinuclear antibody and direct antiglobulin tests support
diagnoses such as systemic lupus erythematosus and immune-mediated anemia,
respectively. Positive tests may occur in cats, but the prevalence of positive
results in healthy cats is not well known. OBJECTIVE: The study's purpose was to
determine prevalences of positive antinuclear antibody and direct antiglobulin
tests in healthy cats. METHODS: Antinuclear antibody titers were measured by
indirect immunofluorescence, and anti-erythrocyte antibodies were measured by the
microtitration direct antiglobulin test at 37, 23, and 4 degrees C in 61 client
owned and 28 facility-owned cats. Differences between the 2 groups were examined
using chi-squared tests. RESULTS: For the antinuclear antibody tests, 70% of
client-owned cats were negative, 10% had weak titers (1:40-1:80), and 20% had
strong titers (1:160-1:320). Facility-owned cats had significantly fewer positive
titers with 96% negative and one positive (1:8). For the antiglobulin test at 37
degrees C, 93% of all cats were negative, 2 cats in each group were positive at
low dilutions (1:2), and 2 client-owned cats were transiently positive at high
dilutions (>= 1:2048). At 23 degrees C, 90% of all cats were negative, and 2
client-owned and 5 facility-owned cats were positive at low dilutions (1:2-1:8).
At 4 degrees C, 67% of client-owned cats had invalid results (negative control
well agglutination), and 33% had negative results, while of facility-owned cats
14% had invalid results, 14% had agglutination at low dilutions, and 72% were
negative. CONCLUSION: Healthy cats may have positive antinuclear antibody and
direct antiglobulin tests, but the prevalence of strong reactions is low.
PMID- 29341178
TI - Security Investment in Contagious Networks.
AB - Security of the systems is normally interdependent in such a way that security
risks of one part affect other parts and threats spread through the vulnerable
links in the network. So, the risks of the systems can be mitigated through
investments in the security of interconnecting links. This article takes an
innovative look at the problem of security investment of nodes on their
vulnerable links in a given contagious network as a game-theoretic model that can
be applied to a variety of applications including information systems. In the
proposed game model, each node computes its corresponding risk based on the value
of its assets, vulnerabilities, and threats to determine the optimum level of
security investments on its external links respecting its limited budget.
Furthermore, direct and indirect nonlinear influences of a node's security
investment on the risks of other nodes are considered. The existence and
uniqueness of the game's Nash equilibrium in the proposed game are also proved.
Further analysis of the model in a practical case revealed that taking advantage
of the investment effects of other players, perfectly rational players (i.e.,
those who use the utility function of the proposed game model) make more cost
effective decisions than selfish nonrational or semirational players.
PMID- 29341179
TI - Better characterization of vinflunine pharmacokinetics variability and
exposure/toxicity relationship to improve its use: Analyses from 18 trials.
AB - AIMS: Vinflunine is a novel tubulin-targeted inhibitor indicated as a single
agent for the treatment of bladder cancers after failure of prior platinum-based
therapy. Its pharmacokinetics (PK) and pharmacodynamics (PD) have been
independently characterized through several phase I and phase II studies.
However, no global pharmacometric analysis had been conducted as yet. METHODS:
Vinflunine concentrations and safety data from 18 phase I and phase II studies
were used to conduct population PK and PK/PD analysis, using Nonmem. A four
compartment model was used to describe vinflunine PK and several covariates were
tested to explain interindividual variability. In terms of PK/PD relationship, a
semiphysiological population PK/PD model was applied to describe time course of
absolute neutrophil counts (ANC) after vinflunine administration and logistic
regression models were used to test the relationship between vinflunine exposure
and toxicities. RESULTS: Vinflunine clearance is explained by creatinine
clearance, body surface area and combination with PEGylated doxorubicin, leading
to a decrease from 28.2 to 25.3% of the interindividual variability. When
vinflunine dose is decreased, simulations of ANC time course (via a
semiphysiological model) after vinflunine administration show a risk of
neutropenia grade 3-4 at cycle 2 always lower than when dose is delayed. As an
example, for moderate renal impaired patients, the risk is 42.1% when vinflunine
is dosed at 320 mg m-2 once every 4 weeks vs. 23.3% for 280 mg m-2 once every 3
weeks. CONCLUSIONS: We propose for the first time a global comprehensive clinical
pharmacological analysis for intravenous vinflunine that may help drive dose
adjustment.
PMID- 29341180
TI - Risk Assessment of Salmonellosis from Consumption of Alfalfa Sprouts and
Evaluation of the Public Health Impact of Sprout Seed Treatment and Spent
Irrigation Water Testing.
AB - We developed a risk assessment of human salmonellosis associated with consumption
of alfalfa sprouts in the United States to evaluate the public health impact of
applying treatments to seeds (0-5-log10 reduction in Salmonella) and testing
spent irrigation water (SIW) during production. The risk model considered
variability and uncertainty in Salmonella contamination in seeds, Salmonella
growth and spread during sprout production, sprout consumption, and Salmonella
dose response. Based on an estimated prevalence of 2.35% for 6.8 kg seed batches
and without interventions, the model predicted 76,600 (95% confidence interval
(CI) 15,400-248,000) cases/year. Risk reduction (by 5- to 7-fold) predicted from
a 1-log10 seed treatment alone was comparable to SIW testing alone, and each
additional 1-log10 seed treatment was predicted to provide a greater risk
reduction than SIW testing. A 3-log10 or a 5-log10 seed treatment reduced the
predicted cases/year to 139 (95% CI 33-448) or 1.4 (95% CI <1-4.5), respectively.
Combined with SIW testing, a 3-log10 or 5-log10 seed treatment reduced the
cases/year to 45 (95% CI 10-146) or <1 (95% CI <1-1.5), respectively. If the SIW
coverage was less complete (i.e., less representative), a smaller risk reduction
was predicted, e.g., a combined 3-log10 seed treatment and SIW testing with 20%
coverage resulted in an estimated 92 (95% CI 22-298) cases/year. Analysis of
alternative scenarios using different assumptions for key model inputs showed
that the predicted relative risk reductions are robust. This risk assessment
provides a comprehensive approach for evaluating the public health impact of
various interventions in a sprout production system.
PMID- 29341181
TI - Baboon syndrome caused by anti-haemorrhoidal ointment.
PMID- 29341182
TI - Allergic contact dermatitis caused by Olanedine(r) (olanexidine gluconate), a new
antiseptic.
PMID- 29341183
TI - Systemic delayed hypersensitivity reaction to chlorambucil: a case report and
literature review.
PMID- 29341184
TI - First report of allergic contact dermatitis caused by sorbitan caprylate.
PMID- 29341185
TI - Comparing patch test results of methylchloroisothiazolinone/methylisothiazolinone
tested with both TRUE Test(r) and 100 ppm using investigator-loaded chambers.
PMID- 29341186
TI - 'Chaturthy fingers' caused by Hibiscus rosasinensis.
PMID- 29341187
TI - Erythema of the penis after use of a latex condom - latex allergy or something
else?
PMID- 29341188
TI - Allergic contact dermatitis caused by hydroxyacetophenone in a face cream.
PMID- 29341189
TI - Is p-phenylenediamine a marker of sulfasalazine allergy?
PMID- 29341190
TI - First case report of acute generalized exanthematous pustulosis (AGEP) caused by
gadolinium confirmed by patch testing.
PMID- 29341191
TI - Working and caring for a child with chronic illness: A review of current
literature.
AB - BACKGROUND: Advances in medical knowledge have contributed to the increase in the
number of children living with some form of long-term chronic illness or
condition. As a consequence of these advancements, treatments that are more
accessible and easier to administer, usually within a child's home, have been
developed. However, this may mean that parents take on greater treatment
responsibility and require extra time and energy to meet these tasks, additional
to other responsibilities. This review paper aims to summarize and critique
existing literature on working parents of children with a chronic condition, by
focusing on patterns of parent work, the challenges experienced, and the flow-on
consequences to well-being. METHODS: Employing a narrative, meta-synthesis of the
current literature, this review identified 3 key themes related to working
parents of children with chronic illness. RESULTS: The paper first identifies
that although employment is less common, these parents are not necessarily
nonworking. Second, these parents experience numerous challenges including
balancing work and family, time constraints, stress, and feelings of "doing it
all." And third, the above challenges lead to additional impacts on parental
quality of life. CONCLUSIONS: This review summarizes what is currently known
about work patterns, challenges, and consequences in parents of children with
chronic conditions. Employment is clearly impacted for these parents. Although
workplace challenges have been extensively researched, other challenges (eg,
personal and family) and impacts on their well-being have not. This review
discusses the present standing of this research. It outlines the strengths and
limitations of the current literature, makes recommendations for future research,
and suggests theoretical and practical implications of the further findings.
PMID- 29341192
TI - Population Pharmacokinetic Modeling of Guselkumab, a Human IgG1lambda Monoclonal
Antibody Targeting IL-23, in Patients with Moderate to Severe Plaque Psoriasis.
AB - Psoriasis is a common inflammatory skin disorder that requires chronic treatment
and is associated with multiple comorbidities. Guselkumab, a human immunoglobulin
G1-lambda monoclonal antibody, binds to interleukin-23 with high specificity and
affinity and is effective in treating moderate to severe plaque psoriasis. As
part of the guselkumab psoriasis clinical trial program, using a confirmatory
approach, a population pharmacokinetics (PopPK) model was established using 13
014 PK samples from 1454 guselkumab-treated patients across 3 phase 2/3 trials.
Observed serum guselkumab concentrations were adequately described by a 1
compartment linear PK model with first-order absorption and elimination. The
final PK model was robust and stable, with apparent clearance (CL/F), apparent
volume of distribution (V/F), and absorption rate constant (ka) estimates of
0.516 L/day, 13.5 L, and 1.11 day-1 , respectively. A model-derived elimination
half-life of 18.1 days indicated achievement of steady-state serum guselkumab
concentrations within 12-14 weeks. The primary covariate contributing to the
observed PK variability was body weight, which accounted for only 28% (CL/F) and
32% (V/F) of the interindividual proportion of variance. Diabetes was identified
to marginally reduce guselkumab exposure, owing to 12% higher CL/F in diabetic
versus nondiabetic patients, but its contribution was not clinically relevant.
None of the other covariates tested (eg, age, sex, ethnicity, immune response to
guselkumab, or concomitant medications) had a clinically relevant effect on
guselkumab exposure.
PMID- 29341193
TI - Impact of Trans-Fats on Heat-Shock Protein Expression and the Gut Microbiota
Profile of Mice.
AB - Partially hydrogenated oils are known to cause metabolic stress and dyslipidemia.
This paper explores a new dimension about the interaction between dietary trans
fats and the defense heat-shock protein (HSP) system, inflammation, and the gut
microbiota of mice consuming a hyperlipidic diet containing partially
hydrogenated vegetable oil free of animal fat. Five diet groups were installed:
control diet, 2 hyperlipidic-partially hydrogenated-oil diets, each containing
either casein or whey-protein hydrolysate (WPH) as protein source, and 2
consuming hyperlipidic-unhydrogenated-oil diets containing either WPH or casein
as a protein source. The partially hydrogenated oil inhibited c-Jun NH2 -terminal
kinase phosphorylation in the casein diets, but without altering kappa-B kinase.
Neither the lipid nor the protein had an influence on the proinflammatory toll
like receptor 4 (TLR4) pathway, but the combination of the high-lipid content and
WPH impaired glucose tolerance without altering insulin or glucose transporter-4
translocation. It was remarkable to observe that, contrary to the case of a
common high-fat diet, the lard-free hyperlipidic diets were hardly able to invert
the Bacteroidetes:Firmicutes phylum ratio. Our results suggest that, in the
absence of lard, the intake of trans-fatty acids is less harmful than expected
because it does not trigger TLR4-inflammation or pose great threat to the normal
gut microbiota. WPH had the effect of promoting the expression of HSP90, HSP60,
and HSP25, but did not prevent dysbiosis, when the diet contained the
unhydrogenated oil. The partially hydrogenated oil also seemed to antagonize the
ability of WPH to induce the expression of protective HSPs.
PMID- 29341194
TI - Generation of red drum (Sciaenops ocellatus) hematology Reference Intervals with
a focus on identified outliers.
AB - BACKGROUND: The Deepwater Horizon (DWH) oil spill in 2010 released millions of
barrels of crude oil into the northern Gulf of Mexico, exposing numerous species
of animals to the toxic components of oil. A comprehensive assessment of
morbidity and mortality caused by DWH oil exposure was undertaken by the DWH
Natural Resource Damage Trustees to characterize ecosystem damages. OBJECTIVES:
This study aimed to characterize normal hematologic RIs in red drum fish with
blood cell descriptions, and to demonstrate the importance of identifying and
removing outliers when generating RI. METHODS: Two years after the oil spill, 57
adult, red drum fish of mixed sexes were caught along the eastern Louisiana
coastline. Eight different sites were chosen to catch the fish; 6 sites were
contaminated with oil, and 2 sites were not contaminated at the time of the oil
spill. Hematologic RIs were generated from heparinized whole blood samples of
healthy red drum as determined by gross examination and histopathologic
examination. Two methods were used to detect hematologic effects likely caused by
oil contamination. RESULTS: Red drum PCVs (RI 42-62%) were higher than previously
reported in cold water and bottom-dwelling fish species, while absolute WBC
counts (RI 2.9-8.7 * 109 /L) were comparable to WBC counts previously reported
in other fish species with heterophil and lymphocyte absolute concentrations
frequently being equivalent. Anemic animals (PCV<42%) were only identified in oil
contaminated sites. CONCLUSION: RIs in many wild fish species are lacking, and
therefore, this study provides valuable baseline data on healthy red drum fish.
The outliers assessed using ASVCP RI guidelines can provide valuable clinical
information regarding individuals in population health assessments, which may be
more sensitive for the detection of abnormalities than for population statistics
comparing the mean. The importance of removing outliers and rerunning RI
statistics is highlighted by this field example.
PMID- 29341195
TI - Association between circulating 25-hydroxyvitamin D levels and psoriasis, and
correlation with disease severity: a meta-analysis.
AB - BACKGROUND: Psoriasis is a chronic, autoimmune, inflammatory skin disorder. 25
hydroxy vitamin D [25(OH)D] deficiency may contribute to the pathogenesis of
psoriasis through reduction in antiproliferative, anti-inflammatory and
antiangiogenic activities. AIM: To evaluate the relationship between circulating
25(OH)D levels and psoriasis, and to determine the correlation between
serum/plasma 25(OH)D levels and psoriasis severity. METHODS: We performed a meta
analysis to compare serum/plasma 25(OH)D levels between patients with psoriasis
and healthy controls (HCs), and to determine the correlation coefficients between
circulating 25(OH)D levels and psoriasis severity as assessed by Psoriasis Area
and Severity Index (PASI). RESULTS: Ten articles with a total of 571 patients
with psoriasis and 496 HCs were included. The 25(OH)D level was significantly
lower in the psoriasis group than in the HC group. Subgroup analysis by sample
size revealed a significantly lower level of 25(OH)D in the psoriasis group for
large (N > 80) but not for small (N < 80) sample sizes. Stratification by
adjustment for age and/or sex or sample type revealed a significantly lower
25(OH)D level in the psoriasis group after adjustment for serum but not after
nonadjustment for plasma. Meta-analysis of the correlation coefficients revealed
a small but statistically significant positive correlation between circulating
25(OH)D levels and PASI. CONCLUSIONS: This meta-analysis demonstrated that
circulating 25(OH)D levels are lower in patients with psoriasis, and that a small
but statistically significant negative correlation exists between 25(OH)D levels
and psoriasis severity.
PMID- 29341196
TI - Dynamic Economic Resilience and Economic Recovery from Disasters: A Quantitative
Assessment.
AB - This article analyzes the role of dynamic economic resilience in relation to
recovery from disasters in general and illustrates its potential to reduce
disaster losses in a case study of the Wenchuan earthquake of 2008. We first
offer operational definitions of the concept linked to policies to promote
increased levels and speed of investment in repair and reconstruction to
implement this resilience. We then develop a dynamic computable general
equilibrium (CGE) model that incorporates major features of investment and traces
the time-path of the economy as it recovers with and without dynamic economic
resilience. The results indicate that resilience strategies could have
significantly reduced GDP losses from the Wenchuan earthquake by 47.4% during
2008-2011 by accelerating the pace of recovery and could have further reduced
losses slightly by shortening the recovery by one year. The results can be
generalized to conclude that shortening the recovery period is not nearly as
effective as increasing reconstruction investment levels and steepening the time
path of recovery. This is an important distinction that should be made in the
typically vague and singular reference to increasing the speed of recovery in
many definitions of dynamic resilience.
PMID- 29341197
TI - How reliable are commercially available trackers in detecting daytime sleep.
PMID- 29341198
TI - Aicardi-Goutieres syndrome: cold-induced acral blemish is not always
cryoglobulinaemic vasculitis or chilblain lupus.
PMID- 29341199
TI - Timing of gamma irradiation and blood donor sex influences in vitro
characteristics of red blood cells.
AB - BACKGROUND: There are few studies investigating the effect of irradiation on red
blood cells (RBCs) during storage. This study analyzed changes in in vitro
quality of RBCs irradiated at several points during storage with the aim of
providing evidence to support current maximum pre- and postirradiation storage
limits. STUDY DESIGN AND METHODS: Each of seven participating centers produced
four pools of 7 standard RBC units (SAGM, AS-3, or PAGGSM), which were then split
back into 7 units. All units in a pool were from sex-matched blood donors. Every
week during 6 weeks of refrigerated storage, 1 unit was irradiated, while 1 unit
was not irradiated (control). Units were tested weekly for biochemical variables,
morphology, and mechanical fragility. RESULTS: The earlier during storage that
units were irradiated, the higher the hemolysis and K+ at end of storage.
Irrespective of the timing of irradiation, there was a rapid increase in
extracellular K+ , followed by a more gradual increase in hemolysis. ATP levels
decreased faster in irradiated units and were reduced below accepted values if
irradiated early. Irradiated female RBCs had an absolute lower hemolysis and K+
level compared to male RBCs at all time points. CONCLUSIONS: The method of blood
component manufacturing determined the absolute levels of hemolysis and potassium
in irradiated and nonirradiated units, but did not influence the effect that
timing of irradiation had on the in vitro quality characteristics. This study
provides support for the current Council of Europe guidelines on the time
limitations for the irradiation of RBCs.
PMID- 29341200
TI - Human Agency in Disaster Planning: A Systems Approach.
AB - Current approaches to risk management place insufficient emphasis on the system
knowledge available to the assessor, particularly in respect of the dynamic
behavior of the system under threat, the role of human agents (HAs), and the
knowledge available to those agents. In this article, we address the second of
these issues. We are concerned with a class of systems containing HAs playing a
variety of roles as significant system elements-as decisionmakers, cognitive
agents, or implementers-that is, human activity systems. Within this family of
HAS, we focus on safety and mission-critical systems, referring to this subclass
as critical human activity systems (CHASs). Identification of the role and
contribution of these human elements to a system is a nontrivial problem whether
in an engineering context, or, as is the case here, in a wider social and public
context. Frequently, they are treated as standing apart from the system in design
or policy terms. Regardless of the process of policy definition followed,
analysis of the risk and threats to such a CHAS requires a holistic approach,
since the effect of undesirable, uninformed, or erroneous actions on the part of
the human elements is both potentially significant to the system output and
inextricably bound together with the nonhuman elements of the system. We present
a procedure for identifying the potential threats and risks emerging from the
roles and activity of those HAs, using the 2014 flooding in southwestern England
and the Thames Valley as a contemporary example.
PMID- 29341201
TI - Diversity in cancer care: exploring social categories in encounters between
healthcare professionals and breast cancer patients.
AB - BACKGROUND: The burden of breast cancer is a key challenge for women's health
globally. Rehabilitation needs and strategies for living with long-term
consequences of breast cancer and its treatment cannot be isolated from the
social contexts of patients, including relationships with relatives and
healthcare professionals. AIM: This study explores how healthcare professionals'
categorisations engage with breast cancer patients' social identities in
encounters about rehabilitation before hospital discharge. METHOD: We conducted a
multiperspective case-based qualitative study at a Danish department of breast
surgery, including participant observations and interviews with twelve patients
and eight nurses. Data were analysed thematically using theories of
categorisation and clinical encounters. Ethical considerations: The Danish Data
Protection Agency approved the study (journal number 2012-41-0701). RESULTS:
Interactions in clinical encounters are shaped by categorisations of patients'
social identities in terms of social resources and ethnicity, and by the resource
constrained organisational context, with impact on the assessments of the
patient's rehabilitation needs. CONCLUSIONS: There is a need for a greater focus
on improving encounters between breast cancer patients and healthcare
professionals to ensure that rehabilitation needs are accommodated for among
diverse patient groups.
PMID- 29341202
TI - Risk factors for stress urinary incontinence recurrence after single-incision
sling.
AB - AIMS: The aim of the study was to identify in a pure stress urinary incontinence
(SUI) population risk factors for recurrence after single-incision slings (SIS).
METHODS: This retrospective study analyzed women with complaints of SUI symptoms
and urodynamically proven SUI. Exclusion criteria were recurrent SUI, overactive
bladder syndrome/detrusor overactivity, preoperative postvoid residual >100 mL,
reduced urethral mobility (<10 degrees at the Q-tip test), concomitant anterior
prolapse >I stage and previous history of radical pelvic surgery. Objective cure
rate was assessed with stress test. RESULTS: A total of 192 patients were
analyzed. Objective cure rate was obtained in 86.5% of patients. According to
univariate analysis, recurrences had higher prevalence of severe ICIQ-SF score
(>=18 points), higher prevalence of reduced urethral mobility (Qtip <=30 degrees
), higher prevalence of low detrusor pressures during voiding phase (opening
pressure <15 cmH2 O, pressure at maximum flow <20 cmH2 O, closing pressure <15
cmH2 O), and higher prevalence of postoperative complications According to
multivariate analysis ICIQ-SF score >=18 points (P = 0.02; OR = 2.7) and detrusor
pressure at maximum flow <20 cmH2 O (P < 0.01; OR = 3.6) resulted as independent
risk factors for SUI recurrence (Table 3). A trend was found for urethral
mobility <=30 degrees (P = 0.07; OR = 2.2). CONCLUSIONS: Our study identifies
SUI severity expressed with ICIQ-SF scores and low detrusor pressure at maximum
flow as independent risk factors for SUI recurrence after SIS implantation while
only a trend was found for reduced urethral mobility. Therefore, preoperative
assessment of symptoms and urodynamics evaluation may play a key role in
improving preoperative counseling and tailoring surgical treatment.
PMID- 29341203
TI - Food specific inhibitory control under negative mood in binge-eating disorder:
Evidence from a multimethod approach.
AB - OBJECTIVE: Inhibitory control has been discussed as a developmental and
maintenance factor in binge-eating disorder (BED). The current study is the first
aimed at investigating inhibitory control in a negative mood condition on a
psychophysiological and behavioral level in BED with a combination of
electroencephalography (EEG) and eye tracking (ET). METHOD: We conducted a
combined EEG and ET study with overweight individuals with BED (BED+, n = 24,
mean age = 31, mean BMI = 35 kg/m2 ) and without BED (BED-, n = 23, mean age =
28, mean BMI = 35 kg/m2 ) and a normal-weight (NWC, n = 26, mean age 28, mean BMI
= 22 kg/m2 ) control group. We assessed self-report data regarding impulsivity
and emotion regulation as well as the processing of food stimuli under negative
mood in an antisaccade task. Main outcome variables comprise event-related
potentials (ERP) regarding conflict processing (N2) and performance monitoring
(error-related negativity [ERN/Ne]) assessed by EEG and inhibitory control
(errors in the first and second saccade) assessed by ET. RESULTS: BED+ patients
reported increased impulsivity and higher emotion regulation difficulties
compared with the other groups. The eye tracking data revealed impaired
inhibitory control in BED+ compared with both control groups. Further, we found
preliminary evidence from EEG recordings that conflict processing might be less
thorough in the BED+ sample as well as in the NWC sample. In the BED+ sample this
might be connected to the inhibitory control deficits on behavioral level. While
the BED- sample showed increased conflict processing latencies (N2 latencies),
which might indicate a compensation mechanism, the BED+ sample did not show such
a mechanism. Performance monitoring (ERN/Ne latencies and amplitudes) was not
impaired in the BED+ sample compared with both control samples. DISCUSSION:
Participants with BED reported higher impulsivity and lower emotion regulation
capacities. The combined investigation of electrocortical processes and behavior
contributes to an advanced understanding of behavioral and electrocortical
processes underlying inhibitory control in BED. Inhibitory control and negative
mood, probably amplified by emotion regulation deficits, should be addressed
further in the investigation and treatment of BED.
PMID- 29341205
TI - Promotion time cure rate model with nonparametric form of covariate effects.
AB - Survival data with a cured portion are commonly seen in clinical trials.
Motivated from a biological interpretation of cancer metastasis, promotion time
cure model is a popular alternative to the mixture cure rate model for analyzing
such data. The existing promotion cure models all assume a restrictive parametric
form of covariate effects, which can be incorrectly specified especially at the
exploratory stage. In this paper, we propose a nonparametric approach to modeling
the covariate effects under the framework of promotion time cure model. The
covariate effect function is estimated by smoothing splines via the optimization
of a penalized profile likelihood. Point-wise interval estimates are also derived
from the Bayesian interpretation of the penalized profile likelihood. Asymptotic
convergence rates are established for the proposed estimates. Simulations show
excellent performance of the proposed nonparametric method, which is then applied
to a melanoma study.
PMID- 29341204
TI - Gender, parental education, and experiences of bullying victimization by
Australian adolescents with and without a disability.
AB - BACKGROUND: This study sought to compare the prevalence of bullying victimization
between adolescents with and without a disability and between adolescents with
and without borderline intellectual functioning or intellectual disability
(BIF/ID). We also sought to assess whether the relationships between either
disability or BIF/ID and bullying victimization vary by gender and parental
education. METHODS: The sample included 3,956 12- to 13-year-old adolescents who
participated in Wave 5 of the Longitudinal Study of Australian Children. Three
indicators of bullying were used: physical bullying victimization, social
bullying victimization, and "any bullying victimization." We used Poisson
regression to obtain the prevalence risk ratios (PRR) of bullying by disability
status adjusting for potential confounders. RESULTS: In adjusted models, we found
evidence that social bullying victimization was more prevalent among adolescents
with a disability than those without a disability (PRR 1.29, 95% confidence
interval [CI] 1.06-1.42) and between adolescents with BIF/ID than those without
(PRR 1.24, 95% CI 1.07-1.44). Adolescents with BIF/ID were also more likely to
experience "any bullying victimization"(PRR 1.10, 95% CI 1.00-1.22). Having a
disability and living in a family with low parental education were associated
with an elevated risk of social bullying victimization BIF/ID. CONCLUSIONS:
Adolescents with disabilities and BIF/ID are at elevated risk of social bullying
victimization. School-based antibullying initiatives should concentrate on
enhancing the inclusion of adolescents with disabilities, with an emphasis on
adolescents from disadvantaged backgrounds.
PMID- 29341207
TI - Letters to the editor.
PMID- 29341206
TI - Validation of a portable monitor for assessment of cerebrospinal fluid lactate in
dogs.
AB - BACKGROUND: Cerebrospinal fluid (CSF) lactate concentration may be a useful
diagnostic and prognostic biomarker in dogs. Previous studies have used methods
requiring relatively large sample volumes or prolonged storage prior to analysis.
An effective method to immediately quantify lactate in smaller CSF volumes would
be beneficial. OBJECTIVES: The main objectives were to evaluate the utility,
accuracy, and precision of a portable meter for CSF lactate analysis in dogs and
to develop a provisional RI using this device. A secondary objective was to
assess the effects of different storage conditions on lactate concentrations.
METHODS: The Lactate Plus device was used to analyze CSF samples. Device accuracy
and precision were assessed by spiking CSF samples with concentrated sodium
lactate solutions and by repeated analysis of samples, respectively. The
provisional RI was generated using CSF samples from dogs with unremarkable
laboratory data, central nervous system imaging, and conventional cytologic and
chemical CSF analysis. Select samples were analyzed before and after storage at 4
degrees C, -20 degrees C, and -80 degrees C. RESULTS: Spiked samples showed
lactate concentrations comparable to expected concentrations. The CV of immediate
repeated measurements was 0-9.69%. Sample storage at 4 degrees C for 24 hours
showed similar results but variation was higher with other storage conditions.
The provisional RI was 1.02-2.49 mmol/L. CONCLUSIONS: The Lactate Plus has
acceptable accuracy and precision for the quantification of CSF lactate in dogs.
Lactate in CSF is ideally quantified immediately after collection as a subset of
samples show variation with storage although most stored samples show acceptable
variation.
PMID- 29341208
TI - Letters to the editor.
PMID- 29341209
TI - Identification of gaps in the current knowledge on pulmonary hypertension in
extremely preterm infants: A systematic review and meta-analysis.
AB - BACKGROUND: Pulmonary hypertension complicates the clinical course of extremely
preterm infants and is associated with bronchopulmonary dysplasia (BPD). However,
prevalence, risk factors, and outcome of pulmonary hypertension in these infants
are insufficiently known. This systematic review and meta-analysis aims to
provide an up-to-date overview of available data on prevalence, risk factors, and
outcome of pulmonary hypertension and to identify current knowledge gaps.
METHODS: Medline, EMBASE, and the Cochrane Library databases were searched in
July 2017. Two authors reviewed titles/abstracts and full-texts. Eligible studies
reported prevalence, patient characteristics or mortality of infants with/without
pulmonary hypertension. Studies were excluded if they did not include extremely
preterm infants. Only similar study samples (selected infants with BPD or infants
both with/without BPD) were compared in the meta-analyses. RESULTS: Of 1829
unique articles identified, 25 were eligible for inclusion. Pulmonary
hypertension was observed in infants with BPD (20%, 95% confidence interval [CI]
14, 25), but also in those without BPD (2%, 95% CI 0, 8). Infants with severe BPD
were most at risk of pulmonary hypertension (risk ratio [RR] 2.7, 95% CI 1.7,
4.2). Infants with pulmonary hypertension were more at risk of mortality (RR 4.7,
95% CI 2.7, 8.3). CONCLUSIONS: Pulmonary hypertension occurs in particularly in
infants with severe BPD, and increases risk of mortality. Due to selected study
populations, heterogeneous pulmonary hypertension-definitions and poorly reported
timing of pulmonary hypertension assessments, however, data available in current
reports are insufficient to allow accurate assessment of true prevalence, risk
factors, and time-related outcome. Prospective studies, with standardised
methodology and follow-up are needed to determine these factors.
PMID- 29341210
TI - Subchorionic Hematoma: Correlation of Grading Techniques With First-Trimester
Pregnancy Outcome.
AB - OBJECTIVES: To evaluate and compare grading systems of subchorionic hematoma
(SCH) on first-trimester ultrasound examinations with live embryos to assess
which best correlates with early pregnancy outcome and to assess the effect of
gestational age at the time of diagnosis on outcome. METHODS: First-trimester
live singleton pregnancies between 6 and 11 weeks' gestational age with SCH were
identified by an institutional database search. First-trimester outcome was
categorized as "live" or "demise" based on ultrasound or medical record
documentation. Hematomas were categorized in 4 ways: (1) subjective (small,
moderate, or large); (2) subjective size based on fraction comparison with
gestational sac size; (3) subjective grading based on the estimated percentage of
the gestational sac surrounded by hematoma; and (4) 3 orthogonal measurements of
the hematoma. RESULTS: A total of 434 sonograms met study inclusion criteria. The
overall rate of first-trimester pregnancy failure was 12.0%. The rate of demise
was significantly higher for hematomas diagnosed at or before 7 weeks (19.6%)
than for those after 8 weeks (3.6%; P < .001). The size of the hematoma estimated
as a fraction of gestational sac size significantly correlated with first
trimester pregnancy loss (P < .001). There was no statistical significance
between first-trimester outcome and the other 2 subjective grading methods.
Volume-based measurements provided spurious results because of the irregular
shape of most hematomas. CONCLUSIONS: Subjective hematoma size based on the
fraction of gestational sac size correlates best with first-trimester pregnancy
outcome. The earlier in pregnancy an SCH is detected, the higher the rate of
subsequent pregnancy failure.
PMID- 29341213
TI - Detection of subclinical left ventricular dysfunction by tissue Doppler imaging
in horses with aortic regurgitation.
AB - BACKGROUND: Aortic regurgitation (AR) can have an important clinical impact and
in some cases leads to left ventricular (LV) failure. Tissue Doppler imaging
(TDI) is an echocardiographic technique that has been used in horses to detect LV
dysfunction. OBJECTIVES: To examine whether TDI detects changes in radial
myocardial wall motion in horses with AR compared with control horses. STUDY
DESIGN: Case-control study. METHODS: Echocardiography was performed in 30 healthy
Warmblood horses and 34 Warmblood horses with AR, subdivided in groups with mild,
moderate or severe AR. TDI measurements were performed on six segments of the
short-axis images of the LV myocardial wall. Myocardial wall motion was evaluated
by measuring velocity and deformation during isovolumetric contraction, systole,
early and late diastole. Timing of different events was also measured. RESULTS:
In most segments, a significantly higher systolic myocardial velocity was found
in horses with AR compared with controls. Horses with AR also had higher late
diastolic velocity, although the difference was not significant in all segments.
TDI measurement of timing intervals demonstrated less difference between groups.
MAIN LIMITATIONS: There was a significant difference in age between the control
group and horses with AR, which may confound the results. The assessment of AR
severity was based on subjective criteria as there is no gold standard.
CONCLUSIONS: TDI showed significant differences in radial systolic and late
diastolic myocardial velocity in horses with AR. This could indicate an altered
LV function in these horses, but further research is needed to investigate the
prognostic value of these measurements.
PMID- 29341212
TI - Differential role of PTEN in transforming growth factor beta (TGF-beta) effects
on proliferation and migration in prostate cancer cells.
AB - BACKGROUND: Transforming growth factor-beta (TGF-beta) acts as a tumor suppressor
in normal epithelial cells but as a tumor promoter in advanced prostate cancer
cells. PI3-kinase pathway mediates TGF-beta effects on prostate cancer cell
migration and invasion. PTEN inhibits PI3-kinase pathway and is frequently
mutated in prostate cancers. We investigated possible role(s) of PTEN in TGF-beta
effects on proliferation and migration in prostate cancer cells. METHODS:
Expression of PTEN mRNA and proteins were determined using RT-PCR and Western
blotting in RWPE1 and DU145 cells. We also studied the role of PTEN in TGF-beta
effects on cell proliferation and migration in DU145 cells after transient
silencing of endogenous PTEN. Conversely, we determined the role of PTEN in cell
proliferation and migration after over-expression of PTEN in PC3 cells which lack
endogenous PTEN. RESULTS: TGF-beta1 and TGF-beta3 had no effect on PTEN mRNA
levels but both isoforms increased PTEN protein levels in DU145 and RWPE1 cells
indicating that PTEN may mediate TGF-beta effects on cell proliferation.
Knockdown of PTEN in DU145 cells resulted in significant increase in cell
proliferation which was not affected by TGF-beta isoforms. PTEN overexpression in
PC3 cells inhibited cell proliferation. Knockdown of endogenous PTEN enhanced
cell migration in DU145 cells, whereas PTEN overexpression reduced migration in
PC3 cells and reduced phosphorylation of AKT in response to TGF-beta. CONCLUSION:
We conclude that PTEN plays a role in inhibitory effects of TGF-beta on cell
proliferation whereas its absence may enhance TGF-beta effects on activation of
PI3-kinase pathway and cell migration.
PMID- 29341215
TI - MicroRNA181c inhibits prostate cancer cell growth and invasion by targeting
multiple ERK signaling pathway components.
AB - BACKGROUND: The ERK signaling pathway is frequently deregulated in tumorigenesis,
mostly by classical mechanisms such as gene mutation of its components (eg, RAS
and RAF). However, whether and how multiple key components of ERK pathway are
regulated by microRNAs are not clear. METHODS: We firstly predicted post
transcriptional regulation of multiple key components of the ERK signaling
pathway by miR181c through bioinformatics analysis, and then confirmed the post
transcriptional regulation by dual luciferase reporter gene assays and Western
blot analysis. The biological effects of miR181c on prostate cancer cell
proliferation, apoptosis, migration, and invasion were measured by CCK-8 assay,
flow cytometry, wound scratch assay, transwell cell migration, and invasion
assays. RESULTS: miR181c post-transcriptionally regulated multiple key members of
the ERK signaling pathway, including extracellular signal-regulated kinase 2
(ERK2), ribosomal S6 kinase 2 (RSK2), serum response factor (SRF), and FBJ murine
osteosarcoma viral oncogene homolog (c-Fos). Ectopic expression of miR181c mimics
effectively suppressed prostate cancer cell proliferation, migration, and
invasion, but promoted cell apoptosis. Furthermore, miR181c treatment combined
with the multi-kinase inhibitor sorafenib significantly enhanced these anti-tumor
effects. CONCLUSIONS: Downregulation of miR181c results in deregulated ERK
signaling and promotes prostate cancer cell growth and metastasis.
PMID- 29341214
TI - Cue reactivity, habituation, and eating in the absence of hunger in children with
loss of control eating and attention-deficit/hyperactivity disorder.
AB - OBJECTIVE: Childhood loss of control (LOC) eating and attention
deficit/hyperactivity disorder (ADHD) are highly comorbid conditions and present
with disordered eating behaviors, such as overeating. This study sought to
delineate shared and specific abnormalities in physiological, cognitive
motivational, and behavioral components of food-specific impulsivity in children
with LOC eating and ADHD. Specifically, children's reactivity and habituation to
food and eating in the absence of hunger were examined. METHODS: Within this
community-based study, four groups of 8-13-year-old children with LOC eating (n =
24), ADHD (n = 32), comorbid LOC eating/ADHD (n = 9), and matched controls (n =
34) received a standard laboratory test meal to establish satiety and were then
exposed to their favorite snack food in a cue exposure/reactivity trial, while
salivation and desire to eat were repeatedly assessed. Subsequently, they were
offered a variety of snack foods ad libitum. RESULTS: Children with LOC eating,
ADHD, and LOC/ADHD did not differ from controls in salivary reactivity and
habituation to food cues. Children with LOC eating and ADHD showed greater cue
reactivity of the desire to eat than controls, but groups did not differ in its
longer-term increments. At free access, only children with LOC/ADHD consumed
significantly more energy than controls. Longer-term increments of desire to eat
predicted greater energy intake beyond LOC/ADHD group status. DISCUSSION: Desire
to eat among children with comorbid LOC eating and ADHD was associated with
overeating in the absence of hunger, which may contribute to excess weight gain.
Delineation of the specific features of childhood LOC eating versus ADHD warrants
further study.
PMID- 29341216
TI - Primary scarring alopecia: A retrospective study of 89 patients in Taiwan.
AB - Primary scarring alopecia (PSA) is caused by irreversible damage to the hair
epithelial stem cells that reside in hair follicles. There is limited published
work regarding PSA amongst the Asian population. The aim of this study was to
evaluate the clinical features and to characterize the subtypes of PSA in
southern Taiwan. In this retrospective case series, we reviewed 89 patients with
pathology-confirmed PSA. The data was collected from National Cheng Kung
University Hospital between 1988 through 2016. The clinical and histological data
were reviewed, and the patients were characterized into different subtypes of PSA
based on the clinical features and histological findings. We noted seven
different subtypes of PSA. The most common type was dissecting cellulitis (DC)
(30.3%), followed by lichen planopilaris (LPP) (23.5%), central centrifugal
cicatricial alopecia (CCCA) (12.4%) and acne keloidalis nuchae (AKN) (12.4%). The
other subtypes include folliculitis decalvans (FD), discoid lupus erythematosus
(DLE) and pseudopelade of Brocq (PPB). Interestingly, FD, DC and AKN were more
common in males, while CCCA, LPP, DLE and PPB had a female predominance. The mean
age of patients with DLE, DC and AKN were younger, while patients with CCCA, LPP,
PPB and FD tend to be older. The pattern of hair loss was more likely to be
unifocal-ragged border in CCCA and DLE, multifocal-interconnected in LPP and FD,
and multifocal-separated in DC. The pathogenesis of PSA may be influenced by sex,
age and genetic background. It is important to identify the hair loss pattern to
differentiate the subtypes of PSA.
PMID- 29341218
TI - Metastatic Crohn's disease in childhood: A case report.
PMID- 29341217
TI - Acetoacetate and ethyl acetoacetate as novel inhibitors of bacterial biofilm.
AB - : Acetoacetate (AAA) was identified as a biofilm inhibitor in a previous study,
where the effect of 190 carbon and nitrogen sources on biofilm amounts by
Escherichia coli O157:H7 was determined. With this study, we tested the effect of
AAA on growth and biofilm amounts of Cronobacter sakazakii, Serratia marcescens
and Yersinia enterocolitica. AAA reduced growth and biofilm amounts of the three
pathogens, albeit at rather high concentrations of 10 to 35 mg ml-1 .
Acetoacetate at a concentration of 5 mg ml-1 reduced Y. enterocolitica mRNA
transcripts of the flagellar master regulator operon flhD, the invasion gene inv,
and the adhesion gene yadA. Transcription of the regulator of plasmid-encoded
virulence genes virF, the plasmid-encoded virulence gene yopQ, and ymoA were
largely unaffected by AAA. Importantly, AAA did not cause an increase in
transcription of any of the tested virulence genes. As a more cost efficient
homologue of AAA, the effect of ethyl acetoacetate (EAA) was tested. EAA reduced
growth, biofilm amounts and live bacterial cell counts up to 3 logs. IC50 values
ranged from 0.31 mg ml-1 to 5.6 mg ml-1 . In summary, both AAA and EAA inhibit
biofilm, but EAA appears to be more effective. SIGNIFICANCE AND IMPACT OF THE
STUDY: Bacterial biofilms are communities of bacteria that form on surfaces and
are extremely difficult to remove by conventional physical or chemical
techniques, antibiotics or the human immune system. Despite advanced
technologies, biofilm still contributes to 60 to 80% of human bacterial
infections (NIH and CDC) and cause problems in many natural, environmental,
bioindustrial or food processing settings. The discovery of novel substances that
inhibit biofilm without increasing the virulence of the bacteria opens doors for
countless applications where a reduction of biofilm is desired.
PMID- 29341219
TI - Current knowledge of nocardiosis in teleost fish.
AB - Nocardia sp. is the causative agent of nocardiosis, a lethal granulomatous
disease of the skin, muscle, and various inner tissues affecting various teleost
and shellfish. Four species of Nocardia have been isolated from diseased fish and
shellfish, namely Nocardia asteroides, Nocardia seriolae, Nocardia salmonicida
and Nocardia crassostreae. Therefore, in fish aquaculture, nocardiosis has caused
severe economic losses, especially in the Asian region. Considerable research has
been performed, since the first report of identified Nocardia sp. in fish, to
characterize Nocardia sp. and identify rapid detection techniques, immune
response against infection and prophylactic approaches. In this review, the
current state of knowledge about nocardiosis in fish has been presented,
including the pathogenesis, diagnosis, host immune response and vaccine
development.
PMID- 29341220
TI - Prevalence of Rhodococcus equi from the nasal cavity of 1010 apparently healthy
horses.
AB - BACKGROUND: Rhodococcus equi is an important cause of foal pneumonia. While its
isolation from different sources has been widely evaluated, there is a need to
better understand the R. equi epidemiology from samples of the nasal cavity of
healthy horses. OBJECTIVES: To determine the prevalence of R. equi from the nasal
cavity of healthy horses, along with its virulence profile, antimicrobial
susceptibility and environmental variables associated. STUDY DESIGN: Cross
sectional study. METHODS: Swabs from the nasal cavity of 1010 apparently healthy
horses from 341 farms were submitted for bacteriological analyses. The identity
and virulence profile of the R. equi isolates were assessed by multiplex PCR;
antimicrobial susceptibility was determined by the disk-diffusion method. The
occurrence of R. equi was calculated at the level of both animal and farm. The
association of seven specific environmental factors with R. equi isolation was
assessed using logistic regression and by a spatial scan statistical method to
determine the presence of local clusters. RESULTS: Antimicrobial-sensitive R.
equi was isolated from 10 (1%) of 1010 horses ranging between 3 and 29 years old.
Ten farms (3%) had at least one positive horse. Only one R. equi isolate (10%)
was classified as virulent. Red-Yellow Argisol (PVA/PV) soils were significantly
associated with R. equi isolation (odds ratio (OR) 8.02; CI95% , 1.98-32.50, P =
0.01), and areas with well-drained soil were less likely to be test positive (OR
0.85; CI95% , 0.76-0.96, P = 0.03). MAIN LIMITATIONS: The use of culture-based
method instead of PCR-based assay and the lack of soil sampling. CONCLUSIONS:
Antimicrobial-sensitive R. equi may be considered a minor part of the normal
bacterial flora in the nasal cavity of healthy and immunologically functional
horses breeding on pasture. Further studies are warranted to determine if soils
rich in iron and well-drained are, in fact, associated with the occurrence of R.
equi.
PMID- 29341221
TI - Pediatric penile porokeratosis: A case report.
AB - We present what we believe to be the second case of pediatric penile
porokeratosis and the youngest case reported. A 6-year-old boy presented with a
pruritic, verrucous growth at the urethral meatus that recurred after two
meatotomies. The diagnosis of porokeratosis was confirmed by biopsy.
Porokeratosis should be added to the differential diagnosis of chronic
hyperkeratotic penile lesions in children.
PMID- 29341223
TI - Disulfide bond based polymeric drug carriers for cancer chemotherapy and relevant
redox environments in mammals.
AB - Increasing numbers of disulfide linkage-employing polymeric drug carriers that
utilize the reversible peculiarity of this unique covalent bond have been
reported. The reduction-sensitive disulfide bond is usually employed as a linkage
between hydrophilic and hydrophobic polymers, polymers and drugs, or as cross
linkers in polymeric drug carriers. These polymeric drug carriers are designed to
exploit the significant redox potential difference between the reducing
intracellular environments and relatively oxidizing extracellular spaces. In
addition, these drug carriers can release a considerable amount of anticancer
drug in response to the reducing environment when they reach tumor tissues,
effectively improving antitumor efficacy. This review focuses on various
disulfide linkage-employing polymeric drug carriers. Important redox thiol pools,
including GSH/GSSG, Cys/CySS, and Trx1, as well as redox environments in mammals,
will be introduced.
PMID- 29341222
TI - 89 Zr-ImmunoPET companion diagnostics and their impact in clinical drug
development.
AB - Therapeutic monoclonal antibodies have been used in cancer treatment for 30
years, with around 24 mAb and mAb:drug conjugates approved by the FDA to date.
Despite their specificity, efficacy has remained limited, which, in part, derails
nascent initiatives towards precision medicine. An image-guided approach to
reinforce treatment decisions using immune positron emission tomography
(immunoPET) companion diagnostic is warranted. This review provides a general
overview of current translational research using Zr-89 immunoPET and
opportunities for utilizing and harnessing this tool to its full potential.
Patient case studies are cited to illustrate immunoPET probes as tools for
profiling molecular signatures. Discussions on its utility in reinforcing
clinical decisions as it relates to histopathological tumor assessment and
standard diagnostic methods, and its potential as predictive biomarkers, are
presented. We finally conclude with an overview of practical considerations to
its utility in the clinic.
PMID- 29341224
TI - Comparative RNA-Seq transcriptome analysis on silica induced pulmonary
inflammation and fibrosis in mice silicosis model.
AB - Silicosis is a long-established public health issue in developing countries due
to increasingly serious air pollution and poorly implemented occupational safety
regulation. Inhalation of silica triggers cytotoxicity, oxidative stress,
pulmonary inflammation and eventually silicosis. Current understanding in the
pathogenesis and mechanism of silicosis is limited, and no effective cure is
clinically available once silicosis is developed. A number of studies were
conducted to investigate silica-induced alternate gene expressions in pulmonary
cells. However, transcriptome analysis in a silicosis animal model is needed.
This study was performed to evaluate the transcriptional alternations in
silicotic mice using comparative RNA-Seq. A silicosis mice model was established
by intratracheal instillation of silica suspensions, and validated by
histological examinations. High-throughput sequencing and differential gene
expression analysis revealed 749 upregulated genes and 70 downregulated genes in
the silicosis model. Genes related to immune cell interactions, immune cell
responses and inflammation were significantly enriched. Cytokine-cytokine
receptor interaction and downstream JAK-STAT signaling pathways were the most
significantly enriched KEGG pathways. Reverse transcription-polymerase chain
reaction analysis and immunohistochemistry were performed to validate further the
differential expression patterns of representative genes. The reported results in
this study provide the basis for elucidating the molecular mechanisms for silica
induced pulmonary inflammation and fibrosis, and support the prevention and
treatment of silicosis.
PMID- 29341225
TI - Past and present mercury accumulation in the Lake Baikal seal: Temporal trends,
effects of life history, and toxicological implications.
AB - Despite global efforts to reduce anthropogenic mercury (Hg) emissions, the
timescale and degree to which Hg concentrations in the environment and biota
respond to decreased emissions remain challenging to assess or predict. In the
present study we characterize long-term trends and life-history patterns in Hg
accumulation and toxicological implications of Hg contamination for a freshwater
seal from one of the world's largest lakes (Lake Baikal, Siberia, Russia) using
contemporary tissues and archival teeth. Stable isotope analysis and Hg analyses
of soft tissues (muscle, liver, kidney, blood, brain, heart) and teeth from 22
contemporary seals revealed rapid changes in diet and Hg accumulation in the
first year of life with a stable diet and increase in tissue Hg throughout the
rest of life. Although maternal transfer of Hg was an important source of Hg to
seal pups, reproduction and lactation by female seals did not appear to result in
sex-related differences in Hg concentrations or age-related accumulation in adult
seals. Based on Hg analysis of archival teeth (n = 114) and reconstructed values
for soft tissues, we also assessed temporal trends in seal Hg between the years
1960 and 2013. Seal Hg concentrations in hard (teeth) and soft (e.g., muscle,
liver) tissues were highest in the 1960s and 1970s, followed by a decrease. The
decline in seal Hg concentrations in recent decades was most likely driven by a
reduction in Hg inputs to the lake, suggesting that global and regional efforts
to reduce Hg emissions have been successful at reducing ecosystem and human
health risks posed by Hg in Lake Baikal. Environ Toxicol Chem 2018;37:1476-1486.
(c) 2018 SETAC.
PMID- 29341226
TI - Molecular details of spontaneous insertion and interaction of HCV non-structure 3
protease protein domain with PIP2-containing membrane.
AB - Hepatitis C virus (HCV), known as the leading cause of liver cirrhosis, viral
hepatitis, and hepatocellular carcinoma, has been affecting more than 150 million
people globally. The HCV non-structure 3 (NS3) protease protein domain plays a
key role in HCV replication and pathogenesis; and is currently a primary target
for HCV antiviral therapy. Through unbiased molecular dynamics simulations which
take advantage of the novel highly mobile membrane mimetic model, we constructed
the membrane-bound state of the protein domain at the atomic level. Our results
indicated that protease domain of HCV NS3 protein can spontaneously bind and
penetrate to an endoplasmic reticulum complex membrane containing
phosphatidylinositol 4,5-bisphosphate (PIP2). An amphipathic helix alpha0 and
loop S1 show their anchoring role to keep the protein on the membrane surface.
Proper orientation of the protein domain at membrane surface was identified
through measuring tilt angles of two specific vectors, wherein residue R161 plays
a crucial role in its final orientation. Remarkably, PIP2 molecules were observed
to bind to three main sites of the protease domain via specific electrostatic
contacts and hydrogen bonds. PIP2-interaction determines the protein orientation
at the membrane while both hydrophobic interplay and PIP2-interaction can
stabilize the NS3 - membrane complex. Simulated results provide us with a
detailed characterization of insertion, orientation and PIP2-interaction of NS3
protease domain at membrane environment, thus enhancing our understanding of
structural functions and mechanism for the association of HCV non-structure 3
protein with respect to ER membranes.
PMID- 29341228
TI - Bronchoalveolar lavage fluid neutrophilia is associated with the severity of
pulmonary lesions during equine asthma exacerbations.
AB - BACKGROUND: The severe form of equine asthma is associated with pathological
changes of the peripheral airways and pulmonary parenchyma that are only partly
described. Also, the relationship between these structural alterations and the
percentage of neutrophils found within the airway lumen, assessed by
bronchoalveolar lavage fluid (BALF) cytology, remains ill-defined. OBJECTIVE: To
examine the histological lesions associated with equine asthma during disease
exacerbation and remission, and their relationship with lung function and BALF
neutrophilia. STUDY DESIGN: Observational retrospective study. METHODS:
Peripheral lung tissues, BALF cytology and lung function data from 61 horses (22
controls, 24 asthma exacerbations and 15 asthma remission) were obtained from an
equine pulmonary tissue bank. Two pathologists semi-quantitatively assessed
histological features, including airway wall inflammation, interstitial fibrosis,
mucus cell hyperplasia, mucostasis, peribronchiolar metaplasia, presence of
granuloma and the overall severity of these lesions. RESULTS: Mucostasis, mucus
cell hyperplasia, peribronchiolar metaplasia and interstitial fibrosis were
associated with disease exacerbation (P<=0.05), and these changes were all
attenuated during remission. Airway wall inflammation was greater in horses with
asthma in exacerbation compared with horses with asthma in remission and control
horses (P<=0.05). Acute (neutrophilic) airway wall inflammation was more
frequently detected in asthmatic cases compared with control horses (P<0.0001)
and was associated with BALF neutrophilia >5% in control horses (P = 0.002). The
degree of bronchiolar inflammation was higher in asthmatic horses in remission
stabled and treated pharmacologically compared with those kept on pasture (P =
0.04). MAIN LIMITATIONS: Samples obtained from a convenient cohort of horses were
studied. CONCLUSIONS: Severely asthmatic horses present parenchymal and
peribronchial/peribronchiolar lesions possibly contributing to the obstructive
nature of the disease.
PMID- 29341229
TI - Assessing and mitigating simulated population-level effects of 3 herbicides to a
threatened plant: Application of a species-specific population model of Boltonia
decurrens.
AB - Extrapolating from organism-level endpoints, as generated from standard pesticide
toxicity tests, to populations is an important step in threatened and endangered
species risk assessments. We apply a population model for a threatened herbaceous
plant species, Boltonia decurrens, to estimate the potential population-level
impacts of 3 herbicides. We combine conservative exposure scenarios with dose
response relationships for growth and survival of standard test species and apply
those in the species-specific model. Exposure profiles applied in the B.
decurrens model were estimated using exposure modeling approaches. Spray buffer
zones were simulated by using corresponding exposure profiles, and their
effectiveness at mitigating simulated effects on the plant populations was
assessed with the model. From simulated exposure effects scenarios that affect
plant populations, the present results suggest that B. decurrens populations may
be more sensitive to exposures from herbicide spray drift affecting vegetative
stages than from runoff affecting early seedling survival and growth. Spray
application buffer zones were shown to be effective at reducing effects on
simulated populations. Our case study demonstrates how species-specific
population models can be applied in pesticide risk assessment to bring organism
level endpoints, exposure assumptions, and species characteristics together in an
ecologically relevant context. Environ Toxicol Chem 2018;37:1545-1555. (c) 2018
SETAC.
PMID- 29341227
TI - PET radiometals for antibody labeling.
AB - Recent advances in molecular characterization of tumors have made possible the
emergence of new types of cancer therapies where traditional cytotoxic drugs and
nonspecific chemotherapy can be complemented with targeted molecular therapies.
One of the main revolutionary treatments is the use of monoclonal antibodies
(mAbs) that selectively target the disseminated tumor cells while sparing normal
tissues. mAbs and related therapeutics can be efficiently radiolabeled with a
wide range of radionuclides to facilitate preclinical and clinical studies. Non
invasive molecular imaging techniques, such as Positron Emission Tomography
(PET), using radiolabeled mAbs provide useful information on the whole-body
distribution of the biomolecules, which may enable patient stratification,
diagnosis, selection of targeted therapies, evaluation of treatment response, and
prediction of dose limiting tissue and adverse effects. In addition, when mAbs
are labeled with therapeutic radionuclides, the combination of immunological and
radiobiological cytotoxicity may result in enhanced treatment efficacy. The
pharmacokinetic profile of antibodies demands the use of long half-life isotopes
for longitudinal scrutiny of mAb biodistribution and precludes the use of well
stablished short half-life isotopes. Herein, we review the most promising PET
radiometals with chemical and physical characteristics that make the appealing
for mAb labeling, highlighting those with theranostic radioisotopes.
PMID- 29341230
TI - Successful treatment of rituximab- and steroid-resistant nephrotic syndrome with
leukocytapheresis.
AB - Although rituximab (RTX) is a promising therapeutic agent for treating steroid
resistant nephrotic syndrome (SRNS) resistant to various immunosuppressive
agents, some patients have shown resistance to RTX. We report the case of a
patient with RTX-resistant nephrotic syndrome and SRNS who was successfully
treated with leukocytapheresis (LCAP). After LCAP, there was a significant
reduction in proteinuria and in the total number of lymphocytes, T cells, and HLA
DR+- activated T cells. Moreover, the patient became sensitive to steroids and
RTX. LCAP reduced circulating immune cells including activated T cells and could
be effective in treating rituximab-resistant nephrotic syndrome and SRNS and in
achieving remission of proteinuria.
PMID- 29341231
TI - Dermoscopic features of Bednar tumor: Report of a case.
PMID- 29341232
TI - Histological features and outcome of inverted type-A melanocytic nevi.
AB - The presence of enlarged epithelioid/spindled nests located deep in the reticular
dermis of a biphasic melanocytic neoplasm can mimic melanoma arising in a pre
existing nevus, causing over-interpretation of malignancy. We aimed to define the
clinicopathologic significance of epithelioid/spindled nests in melanocytic nevi.
Retrospectively using clinical and histologic information, we characterized 121
patients with a single lesion showing epithelioid/spindled melanocytes in the
reticular dermis or subcutaneous fat, surrounded by melanophages, sometimes
blending in with the adnexa. The majority of nevi occurred in women in the ages
of 10 to 39 years, where the most frequent presentation was a changing mole.
While 78% of the lesions displayed an anatomic (Clark's) level of IV-V, there was
no ulceration, significant regression or inflammation. Up to 2 mitoses were found
in only 12% of the cases, not correlating with the severity of cytological
atypia. No recurrence or metastasis occurred during 45.5 months (mean) of
clinical follow up in 26 patients. Notwithstanding the deep dermal extension,
these findings suggest a benign histopathology and clinical outcome. Having
compared the overlapping histopathology and clinical features between deep
penetrating/clonal nevus and combined nevus, we posit that "inverted type-A
nevus" might be considered a variant of the two.
PMID- 29341233
TI - Fate, uptake, and distribution of nanoencapsulated pesticides in soil-earthworm
systems and implications for environmental risk assessment.
AB - Nanopesticides are novel plant protection products offering numerous benefits.
Because nanoparticles behave differently from dissolved chemicals, the
environmental risks of these materials could differ from conventional pesticides.
We used soil-earthworm systems to compare the fate and uptake of analytical-grade
bifenthrin to that of bifenthrin in traditional and nanoencapsulated
formulations. Apparent sorption coefficients for bifenthrin were up to 3.8 times
lower in the nano treatments than in the non-nano treatments, whereas dissipation
half-lives of the nano treatments were up to 2 times longer. Earthworms in the
nano treatments accumulated approximately 50% more bifenthrin than those in the
non-nano treatments. In the non-nano treatments, most of the accumulated material
was found in the earthworm tissue, whereas in the nano treatments, the majority
resided in the gut. Evaluation of toxicokinetic modeling approaches showed that
models incorporating the release rate of bifenthrin from the nanocapsule and
distribution within the earthworm provided the best estimations of uptake from
the nano-formulations. Overall, our findings indicate that the risks of
nanopesticides may be different from those of conventional formulations. The
modeling presented provides a starting point for assessing risks of these
materials but needs to be further developed to better consider the behavior of
the nanoencapsulated pesticide within the gut system. Environ Toxicol Chem
2018;37:1420-1429. (c) 2018 SETAC.
PMID- 29341234
TI - Microangiopathy and acute kidney injury in paroxysmal cold hemoglobinuria: A
challenge for management.
PMID- 29341235
TI - Concomitant cutaneous squamous cell carcinoma and chronic lymphocytic leukemia in
a patient: The utility of 18 F-FDG PET/CT in differentiation of nodal metastasis.
PMID- 29341236
TI - Induced Earthquakes from Long-Term Gas Extraction in Groningen, the Netherlands:
Statistical Analysis and Prognosis for Acceptable-Risk Regulation.
AB - Recently, growing earthquake activity in the northeastern Netherlands has aroused
considerable concern among the 600,000 provincial inhabitants. There, at 3 km
deep, the rich Groningen gas field extends over 900 km2 and still contains about
600 of the original 2,800 billion cubic meters (bcm). Particularly after 2001,
earthquakes have increased in number, magnitude (M, on the logarithmic Richter
scale), and damage to numerous buildings. The man-made nature of extraction
induced earthquakes challenges static notions of risk, complicates formal risk
assessment, and questions familiar conceptions of acceptable risk. Here, a 26
year set of 294 earthquakes with M >= 1.5 is statistically analyzed in relation
to increasing cumulative gas extraction since 1963. Extrapolations from a fast
rising trend over 2001-2013 indicate that-under "business as usual"-around 2021
some 35 earthquakes with M >= 1.5 might occur annually, including four with M >=
2.5 (ten-fold stronger), and one with M >= 3.5 every 2.5 years. Given this uneasy
prospect, annual gas extraction has been reduced from 54 bcm in 2013 to 24 bcm in
2017. This has significantly reduced earthquake activity, so far. However, when
extraction is stabilized at 24 bcm per year for 2017-2021 (or 21.6 bcm, as
judicially established in Nov. 2017), the annual number of earthquakes would
gradually increase again, with an expected all-time maximum M ~ 4.5. Further
safety management may best follow distinct stages of seismic risk generation,
with moderation of gas extraction and massive (but late and slow) building
reinforcement as outstanding strategies. Officially, "acceptable risk" is mainly
approached by quantification of risk (e.g., of fatal building collapse) for
testing against national safety standards, but actual (local) risk estimation
remains problematic. Additionally important are societal cost-benefit analysis,
equity considerations, and precautionary restraint. Socially and psychologically,
deliberate attempts are made to improve risk communication, reduce public
anxiety, and restore people's confidence in responsible experts and policymakers.
PMID- 29341238
TI - Temporal trends in a biomagnifying contaminant: Application of amino acid
compound-specific stable nitrogen isotope analysis to the interpretation of bird
mercury levels.
AB - Temporal trends in levels of biomagnifying contaminants, such as mercury (Hg), in
top predators can provide insights into changes in contaminant bioavailability
through time. However, interpreting contaminant temporal trends in predators can
be confounded by temporal changes in their diets, which, in turn, could affect
organism trophic position and exposure to biomagnifying contaminants. To address
this issue, bulk stable nitrogen isotope analysis, that is, analysis of whole
tissue, is widely incorporated into contaminant-monitoring programs for the
estimation of organism trophic position. In the present study, we investigated
lake-specific temporal trends in Hg levels in herring gull (Larus argentatus
smithsonianus) eggs from Lakes Huron and Erie, 2 Laurentian Great Lakes. Levels
of Hg in Lake Huron eggs declined, whereas Lake Erie eggs showed no change.
Stable nitrogen isotope analysis of bulk material could not explain these
interlake differences in Hg temporal trends. However, application of amino acid
compound-specific stable nitrogen isotope analysis, in conjunction with other
dietary tracers (i.e., fatty acids), provided insights into the factors
regulating interlake differences in Hg temporal trends. Adjusting Hg levels in
predators to account for temporal changes in their diets can have a significant
impact on the interpretation of temporal trend contaminants data. In this case,
it reconciled the apparently different Hg temporal trends observed in gull eggs
from Lakes Huron and Erie. Environ Toxicol Chem 2018;37:1458-1465. (c) 2018
SETAC.
PMID- 29341237
TI - The impact of diuretic use and ABCG2 genotype on the predictive performance of a
published allopurinol dosing tool.
AB - AIM: This research aims to evaluate the predictive performance of a published
allopurinol dosing tool. METHODS: Allopurinol dose predictions were compared to
the actual dose required to achieve serum urate (SU) <0.36 mmol l-1 using mean
prediction error. The influence of patient factors on dose predictions was
explored using multilinear regression. RESULTS: Allopurinol doses were
overpredicted by the dosing tool; however, this was minimal in patients without
diuretic therapy (MPE 63 mg day-1 , 95% CI 40-87) compared to those receiving
diuretics (MPE 295 mg day-1 , 95% CI 260-330, P < 0.0001). ABCG2 genotype
(rs2231142, G>T) had an important impact on the dose predictions (MPE 201, 107,
15 mg day-1 for GG, GT and TT, respectively, P < 0.0001). Diuretic use and ABCG2
genotype explained 53% of the variability in prediction error (R2 = 0.53, P =
0.0004). CONCLUSIONS: The dosing tool produced acceptable maintenance dose
predictions for patients not taking diuretics. Inclusion of ABCG2 genotype and a
revised adjustment for diuretics would further improve the performance of the
dosing tool.
PMID- 29341239
TI - Interaction between healthcare professionals and parents is a key determinant of
parental distress during childhood hospitalisation for respiratory syncytial
virus infection (European RSV Outcomes Study [EROS]).
AB - AIM: We characterised the distress that parents experienced when their child was
hospitalised for respiratory syncytial virus (RSV) infection. METHODS: This
survey-based, observational study was conducted during 2014-2015. Meetings were
held in Spain and Italy, with 24 parents of RSV hospitalised infants and 11
healthcare professionals experienced in RSV, which identified 110 factors related
to parental distress. The resulting questionnaire was completed by another 105
Spanish and Italian parents and 56 healthcare professionals, to assess the impact
these factors had on parental distress, using a scale from 0 to 10 (very
unimportant to very important). RESULTS: The five most important factors for
parents were: healthcare professionals' awareness of the latest developments,
readmission, reinfections, painful procedures and positive experiences with
healthcare professionals. Healthcare professionals associated only medical
factors with a meaningful impact on parents. Half of the six medical factors were
given similar importance by both groups and the overall scoring for the 110
factors was comparable, with a correlation coefficient of 0.80. A primary concern
on discharge was ongoing support. CONCLUSION: The relationship between parents
and healthcare professionals was a significant factor in determining parental
distress. Healthcare professionals appeared to have a good understanding of the
overall impact on parents, particularly the key medical factors.
PMID- 29341240
TI - A case report and literature review of autism and attention deficit hyperactivity
disorder in paediatric chronic pain.
AB - : Psychiatric disorders are common in paediatric patients with chronic pain, but
the overall prevalence of comorbid neurodevelopmental disorders is unclear. We
report on a case of severe chronic pain in a child with undiagnosed comorbid
autism spectrum disorder and attention deficit hyperactivity disorder, where
significant improvements in pain and function occurred following methylphenidate
medication and parental behavioural training. CONCLUSION: The inclusion of
behavioural assessment and screening for neurodevelopmental comorbidity may be
essential in addressing complex paediatric chronic pain.
PMID- 29341241
TI - Pan-pseudothrombocytopenia: An unusual case of platelet clumping.
PMID- 29341242
TI - Acute generalized exanthematous pustulosis induced by a digestive enzyme drug,
Festal(r).
PMID- 29341243
TI - Subcutaneous basal cell carcinoma.
PMID- 29341244
TI - Re: Challenges in research on pregnancy termination and ethical considerations.
PMID- 29341245
TI - Pharmacokinetic/pharmacodynamic drug-drug interactions of avatrombopag when
coadministered with dual or selective CYP2C9 and CYP3A interacting drugs.
AB - AIMS: Avatrombopag, a thrombopoietin receptor agonist, is a substrate of
cytochrome P450 (CYP) 2C9 and CYP3A. We assessed three drug-drug interactions of
avatrombopag as a victim with dual or selective CYP2C9/3A inhibitors and
inducers. METHODS: This was a three-part, open-label study. Forty-eight healthy
subjects received single 20 mg doses of avatrombopag alone or with one of 3
CYP2C9/3A inhibitors or inducers: fluconazole 400 mg once daily for 16 days,
itraconazole 200 mg twice daily on Day 1 and 200 mg once daily on Days 2-16, or
rifampicin 600 mg once daily for 16 days. Pharmacokinetics, pharmacodynamics
(platelet count) and safety of avatrombopag were evaluated. RESULTS:
Coadministration of a single 20-mg dose of avatrombopag with fluconazole at
steady-state resulted in 2.16-fold increase of AUC of avatrombopag, prolonged
terminal elimination phase half-life (from 19.7 h to 39.9 h) and led to a
clinically significant increase in maximum platelet count (1.66-fold).
Itraconazole had a mild increase on both avatrombopag pharmacokinetics and
pharmacodynamics compared to fluconazole. Coadministration of rifampicin caused a
0.5-fold decrease in AUC and shortened terminal elimination phase half-life (from
20.3 h to 9.84 h), but has no impact on maximum platelet count. Coadministration
with interacting drugs was found to be generally safe and well-tolerated.
CONCLUSIONS: The results from coadministration of fluconazole or itraconazole
suggest that CYP2C9 plays a more predominant role in metabolic clearance of
avatrombopag than CYP3A. To achieve comparable platelet count increases when
avatrombopag is coadministered with CYP3A and CYP2C9 inhibitors, an adjustment in
the dose or duration of treatment is recommended, while coadministration with
strong inducers is not currently recommended.
PMID- 29341246
TI - Risk factors for disordered weight control behaviors among Korean adolescents:
Multilevel analysis of the Korea Youth Risk Behavior Survey.
AB - OBJECTIVE: To investigate the prevalence and risk factors for disordered weight
control behaviors (DWCB) in South Korean adolescents at multiple levels,
including individual, family, school, and geographic area. METHOD: We drew
participants from the 11th Korea Youth Risk Behavior Web-based Survey, conducted
in 2015, with 65,529 adolescents (31,687 girls, 33,842 boys) aged 12-18 years.
DWCB was defined as engaging in any of the following behaviors for weight control
over the past month: fasting, one-food diet (eating only one food over an
extended period of time for weight control), vomiting, and taking
laxatives/diuretics/unprescribed diet pills. Sex-stratified four-level multilevel
logistic models examined potential predictors of DWCB, including age, body-mass
index, puberty, perceived household economic status, parental education, living
structure, school type and sex-composition, percentage of students participating
in school nutrition programs, and urbanicity. RESULTS: Overall, 6.2% of Korean
adolescents (8.9% of girls, 3.7% of boys) exhibited any DWCB. We found
significant between-school variation among girls and boys and between-classroom
variation among girls. Older age, overweight/obesity, pubertal maturity, high
household economic status (vs. mid-range economic status), and vocational
schooling (vs. general) were positively associated with DWCB among girls and
boys. Low household economic status (vs. mid-range economic status), higher
parental education, and coeducational schooling (vs. single-sex) were positively
associated with DWCB among girls only. DISCUSSION: The findings suggest that DWCB
are prevalent among Korean adolescents across age, sex, and socioeconomic status.
Social contextual factors including school and familial environmental factors, as
well as individual characteristics, should be considered when developing
effective prevention strategies.
PMID- 29341248
TI - Are kidney transplantation outcomes improved in children weighting 15 kilograms
or less in the last decades?
PMID- 29341249
TI - Reconstruction of an upper posterior thigh extensive defect with a free split
anterolateral thigh (s-ALT) flap by perforator-to-perforator anastomosis: A case
report.
AB - The anterolateral thigh (ALT) flap is one of the most commonly used flap
worldwide in reconstructive surgery, as both free flap and pedicled local flap.
Here, we report the use of a free split anterolateral thigh (s-ALT) flap for
reconstruction of a 14 cm * 16 cm soft tissue defect of the left upper posterior
thigh region due to sarcoma resection in a patient. The ALT flap was harvested
based on two musculocutaneous perforators from the right thigh and anastomosed to
the contralateral descending branch of the lateral circumflex femoral artery
(LCFA) in perforator-to-perforator manner, in order to gain more pedicle length
and being able to cover the posterior thigh defect. The post-operative course was
uneventful and the patient was discharged at 1 week post-operative. Eleven months
after the operation, the aesthetic outcome was satisfactory with no functional
deficit. Even though it requires technical skills and experience in perforator
dissection, we believe that the s-ALT flap anstomosed to the contralateral LCFA
in perforator to perforator fashion, may be a good solution in case of such a
difficultly located extensive defect of the posterior thigh.
PMID- 29341247
TI - Secretory expression of negative regulatory region of human Notch1 in Escherichia
coli and preparation of a functional polyclonal antibody.
AB - Notch signaling is a highly conserved pathway existed in multicellular organisms.
It plays roles in normal human body development, human cancer initiation,
progression and metastasis. The Notch negative regulatory region (NRR) is
critical for Notch signaling, and cleavage at the S2 site in the NRR ultimately
leads to the activation of Notch signaling. To study the function of human NRR1,
we expressed the recombinant human NRR1 (rhNRR1) domain in Escherichia coli.
After purification, rhNRR1 was obtained with approximately 94% purity according
to SDS-PAGE analysis. Furthermore, the polyclonal anti-rhNRR1 serum raised by
immunizing mouse with the purified rhNRR1 was able to reduce the generation of
active form of Notch1 intracellular domain in HeLa cells, which implied the
raised antibody could recognize and bind the natural conformation of Notch1 NRR.
Preparation of rhNRR1 by this way is convenient, time-consuming, and could be
used to the preparation of anti-NRR1 therapeutic antibody.
PMID- 29341250
TI - Protectiveness of Cu water quality criteria against impairment of behavior and
chemo/mechanosensory responses: An update.
AB - A meta-analysis was conducted of studies that reported behavior and
chemo/mechanosensory responses by fish, amphibians, and aquatic invertebrates in
Cu-containing waters and also reported sufficient water chemistry for calculation
of hardness-based and biotic ligand model (BLM)-based water quality criteria
(WQC) for Cu. The calculated WQC concentrations were then compared with the
corresponding 20% impairment concentrations (IC20) of Cu for those behavior and
chemo/mechanosensory responses. The hardness-based acute and chronic WQC for Cu
would not have been protective (i.e., the IC20 would have been lower than the
WQC) in 33.6 and 26.2%, respectively, of the 107 combined behavior- and
chemo/mechanosensory-response cases that also had adequate water chemistry data
for BLM-based WQC calculations (32.7% inconclusive). In comparison, the BLM-based
acute and chronic WQC for Cu would not have been protective in only 10.3 and
4.7%, respectively, of the same 107 cases (29.9% inconclusive). To improve
evaluations of regulatory effectiveness, researchers conducting aquatic Cu
toxicity tests should measure and report complete BLM-input water chemistry and
bracket the hardness-based and BLM-based WQC concentrations for Cu that would be
applicable in their exposure waters. This meta-analysis demonstrates that,
overall, the BLM-based WQC for Cu were considerably more protective than the
hardness-based WQC for Cu against impairment of behavior and chemo/mechanosensory
responses. Environ Toxicol Chem 2018;37:1260-1279. (c) 2018 SETAC.
PMID- 29341251
TI - Residue packing in globular and intrinsically disordered proteins.
AB - Intrinsically disordered proteins (IDPs)/regions do not have well-defined
secondary and tertiary structures, however, they are functional and it is
critical to gain a deep understanding of their residue packing. The shape
distributions methodology, which is usually utilized in pattern recognition,
clustering, and classification studies in computer science, may be adopted to
study the residue packing of the proteins. In this study, shape distributions of
the globular proteins and IDPs were obtained to shed light on the residue packing
of their structures. The shape feature that was used is the sphericity of
tetrahedra obtained by Delaunay Tessellation of points of Calpha coordinates.
Then the sphericity probability distributions were compared by using Principal
Component Analysis. This computational structural study shows that the set of
IDPs constitute a more diverse set than the set of globular proteins in terms of
the geometrical properties of their network structures.
PMID- 29341252
TI - Painful procedures can affect post-natal growth and neurodevelopment in preterm
infants.
AB - AIM: This Italian study evaluated whether painful procedures during the first
four weeks of life were related to subsequent weight gain, head circumference
(HC) and neurodevelopmental outcomes in preterm infants, METHODS: We evaluated
the number of invasive procedures that infants born at less than 32 weeks of
gestational age (GA) underwent in the Neonatal Intensive Care Unit of Careggi
Hospital, Florence, from January to December 2015. Weight and HC were recorded at
birth, 36 weeks of PMA and six and 12 months of CA. Neurological outcomes were
assessed at six and 12 months of CA using the Bayley Scales of Infant and Toddler
Development - Third Edition. RESULTS: We studied 83 preterm infants with a GA of
28 +/- 2 weeks and birth weight of 1098 +/- 340 g. A higher number of invasive
painful procedures were related to a lower HC standard deviation score at 36
weeks of PMA and six and 12 months of CA and with lower cognitive scores at six
months. At 12 months, the relationship only remained significant for infants born
at less than 28 weeks (p < 0.001). CONCLUSION: Invasive painful procedures
affected regular HC growth and short-term cognitive scores in preterm infants in
the first year of life.
PMID- 29341253
TI - A generalized Blaschko linear congenital eruption.
PMID- 29341254
TI - Do Cutibacterium acnes and Staphylococcus aureus define two different types of
folliculitis?: Bacteriological study of scalp folliculitis.
PMID- 29341255
TI - Data-assisted protein structure modeling by global optimization in CASP12.
AB - In CASP12, 2 types of data-assisted protein structure modeling were experimented.
Either SAXS experimental data or cross-linking experimental data was provided for
a selected number of CASP12 targets that the CASP12 predictor could utilize for
better protein structure modeling. We devised 2 separate energy terms for SAXS
data and cross-linking data to drive the model structures into more native-like
structures that satisfied the given experimental data as much as possible. In
CASP11, we successfully performed protein structure modeling using simulated
sparse and ambiguously assigned NOE data and/or correct residue-residue contact
information, where the only energy term that folded the protein into its native
structure was the term which was originated from the given experimental data.
However, the 2 types of experimental data provided in CASP12 were far from being
sufficient enough to fold the target protein into its native structure because
SAXS data provides only the overall shape of the molecule and the cross-linking
contact information provides only very low-resolution distance information. For
this reason, we combined the SAXS or cross-linking energy term with our regular
modeling energy function that includes both the template energy term and the de
novo energy terms. By optimizing the newly formulated energy function, we
obtained protein models that fit better with provided SAXS data than the X-ray
structure of the target. However, the improvement of the model relative to the 1
modeled without the SAXS data, was not significant. Consistent structural
improvement was achieved by incorporating cross-linking data into the protein
structure modeling.
PMID- 29341256
TI - Case of classic Kaposi sarcoma of the penis successfully treated with
radiotherapy.
PMID- 29341257
TI - Bottom-Up Fabrication of Semiconductive Metal-Organic Framework Ultrathin Films.
AB - Though generally considered insulating, recent progress on the discovery of
conductive porous metal-organic frameworks (MOFs) offers new opportunities for
their integration as electroactive components in electronic devices. Compared to
classical semiconductors, these metal-organic hybrids combine the crystallinity
of inorganic materials with easier chemical functionalization and processability.
Still, future development depends on the ability to produce high-quality films
with fine control over their orientation, crystallinity, homogeneity, and
thickness. Here self-assembled monolayer substrate modification and bottom-up
techniques are used to produce preferentially oriented, ultrathin, conductive
films of Cu-CAT-1. The approach permits to fabricate and study the electrical
response of MOF-based devices incorporating the thinnest MOF film reported thus
far (10 nm thick).
PMID- 29341258
TI - Utility of ultrasonography in hair-thread tourniquet syndrome.
AB - A 2-year-old girl presented with a 2-month history of an erythematous, indurated
plaque with well-defined borders on the third toe of the right foot. Bedside high
resolution ultrasonography demonstrated a thickened epidermis overlying a
hyperechoic focus within the dermis. Her clinical and sonographic presentation
was in keeping with a foreign body causing hair-thread tourniquet syndrome. The
foreign body was surgically extirpated without neurovascular sequelae.
Ultrasonography expedited accurate diagnosis and is a promising adjunct to
clinical evaluation for radiolucent foreign bodies.
PMID- 29341259
TI - CHILD syndrome mimicking verrucous nevus in a Chinese patient responded well to
the topical therapy of compound of simvastatin and cholesterol.
AB - BACKGROUND: Congenital hemidysplasia with ichthyosiform erythroderma and limb
defects (CHILD) syndrome is a rare X-linked dominant disorder characterized by
peculiar cutaneous presentations and ipsilateral skeletal abnormalities. CHILD
syndrome is caused by mutations in NSDHL gene, which involves in cholesterol
synthesis. OBJECTIVES: To verify the diagnosis of CHILD syndrome and seek
effective pathogenesis-based therapy with little side-effects. METHOD: We
comprehensively evaluated the patient's conditions. Pathological biopsy was
performed in the lesion location. Genetic tests and real-time quantitative PCR
were conducted to further confirm the diagnosis. The topical application of a
mixed lotion containing 2% simvastatin and 2% cholesterol to lesion areas based
on the pathogenesis as well as the literature review. RESULTS: We diagnosed a
rare and typical case of CHILD syndrome co-occurring with multiple VX-like
lesions. The gene mutation is a large deletion of exon 3 and 4 of the NSDHL gene,
which was discovered and reported for the first time in CHILD syndrome. The skin
lesions, including the verruciform plaques and VX-like lesions, improved
obviously after treatment. CONCLUSIONS: Multiple exons deletions or microdeletion
was not rare in CHILD syndrome. Classical Sanger sequencing may not be useful
enough to find all kinds of mutations. Next-generation sequencing may be more
effective. It is important to conduct genetic counselling to prevent more serious
defects in descendants. The excellent therapeutic effect on CHILD syndrome
resulted from the topical treatment with simvastatin/cholesterol provides a proof
of-concept for other topical pathogenesis-based therapies for skin disease.
PMID- 29341260
TI - Essential oils improved weight gain, growth and feed efficiency of young dairy
calves fed 18 or 20% crude protein starter diets.
AB - The objective was to evaluate interactions between starter protein (180 vs. 200
g/kg, DM basis) and a mixture of essential oils (EOs; containing thymol, eugenol,
vanillin, limonene and guaiacol) on growth, metabolic and ruminal functions of
Holstein dairy calves. In a completely randomized 2 * 2 factorial design, 48
calves, 3 days old (averaging BW 42.7 +/- 1.9 kg), were allocated into groups fed
the following diets: (i) 180 g/kg CP with no EO (180P-NEO); (ii) 180 g/kg CP with
EO (180P-EO); (iii) 200 g/kg CP with no EO (200P-NEO); and (iv) 200 g/kg CP with
EO (200P-EO). The EO was supplemented as 1 g/kg of starter DM. Calves were fed ad
libitum starter diet and were weaned at day 59 of age, but diets continued until
day 80. There were no interactive effects of CP and EO on intake and growth. Pre
weaning feed efficiency tended to be increased for 200P-EO (p = .09). Average
daily gain and feed efficiency during pre-weaning period as well as weaning
weight were increased (p < .05) by EO, whereas wither height was increased by EO
(p = .03) and tended to be increased for 200P vs. 180P (p = .06). Post-weaning
blood urea nitrogen concentration tended to be lower in 180P vs. 200P (p = .08).
Ruminal short-chain fatty acids concentration was greatest in 200P-EO. The EO
increased both butyrate (p = .02) and propionate proportions (p = .01) and
reduced acetate proportional ratio (p < .01). Ruminal ammonia-N was tended to be
lower in calves-fed EO (p = .05) and was lower in those fed 180P vs. 200P (p <
.01). In conclusion, supplementation of the starter diet with essential oil
improved weight gain, growth and feed efficiency of dairy calves, irrespective of
dietary protein content.
PMID- 29341261
TI - Consensus statements on the clinical understanding and use of milnacipran in Hong
Kong.
AB - OBJECTIVE: Our aim is to develop a local consensus to guide medical practitioners
and psychiatrists on the use of milnacipran in different psychiatric conditions.
METHODS: By utilizing the modified Delphi technique, 12 statements were
electronically voted on anonymously for their practicability of recommendation.
RESULTS: There was a very high degree of agreement among the consensus group on
10 finalized consensus statements, but 2 statements were voted down due to a poor
degree of agreement. CONCLUSIONS: The present consensus statements were developed
as general recommendations for medical practitioners and psychiatrists to be
practically referred to in clinical settings.
PMID- 29341262
TI - Reversine inhibits MMP-1 and MMP-3 expressions by suppressing of ROS/MAPK/AP-1
activation in UV-stimulated human keratinocytes and dermal fibroblasts.
AB - UVB has been shown to stimulate the generation of reactive oxygen species (ROS),
which subsequently results in the activation of various intracellular signalling
pathways and transcription factors (AP-1, NF-kappaB). These transcription factors
are regulated by MAPKs, which increase cytokine and MMP expression. We examined
the preventive effects of reversine on MMP-1 and MMP-3 expressions in NHEKs and
NHDFs exposed to UVB irradiation. Also, we confirmed that reversine decreased pro
inflammatory cytokine expression in NHEKs. The mechanism underlying the MMP
inhibitory effects of reversine occurred via the suppression of UVB-induced ROS
generation and MAPK/AP-1 activation. Therefore, reversine is an effective
therapeutic candidate for preventing skin photoageing.
PMID- 29341264
TI - A Facile Method to Fabricate Anisotropic Hydrogels with Perfectly Aligned
Hierarchical Fibrous Structures.
AB - Natural structural materials (such as tendons and ligaments) are comprised of
multiscale hierarchical architectures, with dimensions ranging from nano- to
macroscale, which are difficult to mimic synthetically. Here a bioinspired,
facile method to fabricate anisotropic hydrogels with perfectly aligned
multiscale hierarchical fibrous structures similar to those of tendons and
ligaments is reported. The method includes drying a diluted physical hydrogel in
air by confining its length direction. During this process, sufficiently high
tensile stress is built along the length direction to align the polymer chains
and multiscale fibrous structures (from nano- to submicro- to microscale) are
spontaneously formed in the bulk material, which are well-retained in the
reswollen gel. The method is useful for relatively rigid polymers (such as
alginate and cellulose), which are susceptible to mechanical signal. By
controlling the drying with or without prestretching, the degree of alignment,
size of superstructures, and the strength of supramolecular interactions can be
tuned, which sensitively influence the strength and toughness of the hydrogels.
The mechanical properties are comparable with those of natural ligaments. This
study provides a general strategy for designing hydrogels with highly ordered
hierarchical structures, which opens routes for the development of many
functional biomimetic materials for biomedical applications.
PMID- 29341263
TI - Dermoscopy vs. reflectance confocal microscopy for the diagnosis of lentigo
maligna.
AB - BACKGROUND: Several dermoscopic and in vivo reflectance confocal microscopy (RCM)
diagnostic criteria of lentigo maligna (LM)/lentigo maligna melanoma (LMM) have
been identified. However, no study compared the diagnostic accuracy of these
techniques. OBJECTIVE: We evaluated the diagnostic accuracy of dermoscopy and RCM
for LM/LMM using a holistic assessment of the images. METHODS: A total of 223
facial lesions were evaluated by 21 experts. Diagnostic accuracy of the clinical,
dermoscopic and RCM examination was compared. Interinvestigator variability and
confidence level in the diagnosis were also evaluated. RESULTS: Overall
diagnostic accuracy of the two imaging techniques was good (area under the curve
of the sROC function: 0.89). RCM was more sensitive (80%, vs. 61%) and less
specific (81% vs. 92%) than dermoscopy for LM/LMM. In particular, RCM showed a
higher sensitivity for hypomelanotic and recurrent LM/LMM. RCM had a higher
interinvestigator agreement and a higher confidence level in the diagnosis than
dermoscopy. CONCLUSION: Reflectance confocal microscopy and dermoscopy are both
useful techniques for the diagnosis of facial lesions and in particular LM/LMM.
RCM is particularly suitable for the identification of hypomelanotic and
recurrent LM/LMM.
PMID- 29341265
TI - Cicatricial Alopecia Research Foundation meeting, May 2016: Progress towards the
diagnosis, treatment and cure of primary cicatricial alopecias.
AB - Primary cicatricial alopecias (PCAs) are a group of skin diseases in which there
is progressive and permanent destruction of hair follicles followed by
replacement with fibrous tissue. Unfortunately, by the time patients seek
clinical evaluation of their hair loss, the skin is already inflamed and/or
scarred, so there is little hope for a return to their normal hair growth
pattern. Clinical and basic science investigations are now focusing on three
forms of human PCA: lichen planopilaris (LPP), frontal fibrosing alopecia (FFA)
and central centrifugal cicatricial alopecia (CCCA). Transcriptome, lipidome and
other new technologies are providing new insight into the pathogenesis of some of
these diseases that are being validated and further investigated using
spontaneous and genetically engineered mouse models.
PMID- 29341266
TI - Merkel cell carcinoma in France: a registries-based, comprehensive
epidemiological survey.
AB - BACKGROUND: Merkel cell carcinoma (MCC) is a rare primary cutaneous
neuroendocrine carcinoma. Owing to its low incidence, epidemiological data are
scarce and have never been analysed in France to identify the main
epidemiological trends. METHODS: Data from MCC patients diagnosed between 1998
and 2010 were obtained from 11 French cancer registries in the FRANCIM network.
The main epidemiological characteristics of MCC were investigated between 2006
and 2010 because comprehensive data were only available for this period. The main
focus was tumour incidence and mortality over time. RESULTS: Between 1998 and
2010, 562 cases of MCC were reported in the registries. From 2006 to 2010 (290
cases), European- and world-standardized incidence rates were 0.26 and 0.43 per
100,000 person-years in men and 0.24 and 0.38 per 100,000 person-years in women.
MCC is more frequent in females in France (56.9%) with male/female ratio 1.1.
Relative survival rates were 84%, 56% and 42% at one, three and 5 years,
respectively. CONCLUSIONS: The incidence of MCC clearly increased over time in
all areas under focus. The standardized incidence in France was comparable to the
incidence observed in other countries for the same period, but French data are
too recent to conclude on an increase in MCC incidence. Prognosis remains poor in
all countries in which data are available.
PMID- 29341267
TI - Cross-Linking of Thiolated Paclitaxel-Oligo(p-phenylene vinylene) Conjugates
Aggregates inside Tumor Cells Leads to "Chemical Locks" That Increase Drug
Efficacy.
AB - How to reduce the resistance of certain tumor cells to paclitaxel (PTX) and
related taxoid anticancer drugs is a major challenge for improving cure rates. An
oligo(p-phenylenevinylene) unit with thiol groups and a PTX unit (OPV-S-PTX),
which enhances drug efficacy and reverses resistance is thus designed. The
mechanism involves diffusion of OPV-S-PTX into the cell, where pi-pi interactions
lead to aggregation. Cross-linking of the aggregates via oxidation of thiol
groups is favored in tumor cells because of the higher reactive oxygen species
(ROS) concentration. Cross-linked aggregates "chemically lock" the
multichromophore particle for a more persistent effect. The IC50 of OPV-S-PTX for
tumor cell line A549 is reduced down to 0.33 * 10-9 m from that observed for PTX
itself (41 * 10-9 m). Enhanced efficacy by OPV-S-PTX is proposed to proceed via
acceleration of microtubule bundle formation. A549/T-inoculated xenograft mice
experiments reveal suppression of tumor growth upon OPV-S-PTX treatment.
Altogether, these results show that the internal cross-linking of OPV-S-PTX
through ROS provides a means to discriminate between tumor and healthy cells and
the formation of the chemically locked particles enhances drug efficacy and helps
in reducing resistance.
PMID- 29341268
TI - Evans syndrome secondary to undiagnosed chronic lymphocytic leukemia in a patient
with unexplained bleeding.
PMID- 29341271
TI - Review shows that early foetal alcohol exposure may cause adverse effects even
when the mother consumes low levels.
AB - AIM: Studies are increasingly focusing on the effects of prenatal alcohol
exposure (PAE) on child health. The aim of this review was to provide
paediatricians with new insights to help them communicate key messages about
avoiding alcohol during pregnancy. METHODS: Inspired by the 7th International
Conference on Fetal Alcohol Spectrum Disorder, which focused on integrating
research, policy and practice, we studied English language papers published since
2010 on how early PAE triggered epigenetic mechanisms that had an impact on the
development of some chronic diseases. We also report the findings of a human
study using three-dimensional photography of the face to explore associations
between PAE and craniofacial phenotyping. RESULTS: Animal models with different
alcohol exposure patterns show that early PAE may lead to long-term chronic
effects, due to developmental programming for some adult diseases in
cardiovascular, metabolic and renal systems. The study with three-dimensional
photographing is very promising in helping paediatricians to understand how even
small amounts of PAE can affect craniofacial phenotyping. CONCLUSION: Even low
levels of PAE can cause adverse foetal effects and not just in the brain. It is
not currently possible to determine a safe period and level when alcohol
consumption would not affect the foetus.
PMID- 29341270
TI - Pretransplant depression in lung recipients - a lost battle?
PMID- 29341272
TI - Editorial: getting bullish about portal hypertension-chronic treatment with oral
taurine?
PMID- 29341269
TI - Characterization of a 3xTg-AD mouse model of Alzheimer's disease with the
senescence accelerated mouse prone 8 (SAMP8) background.
AB - No model fully recapitulates the neuropathology of Alzheimer's disease (AD).
Although the triple-transgenic mouse model of AD (3xTg-AD) expresses Abeta
plaques and tau-laden neurofibrillary tangles, as well as synaptic and behavioral
deficits, it does not display frank neuronal loss. Because old age is the most
important risk factor in AD, senescence-related interactions might be lacking to
truly establish an AD-like environment. To investigate this hypothesis, we bred
the 3xTg-AD mouse with the senescence-accelerated mouse prone 8 (SAMP8), a model
of accelerated aging. We generated four groups of heterozygous mice with either
the SAMP8 or SAMR1 (senescence-resistant-1) genotype, along with either the 3xTg
AD or non-transgenic (NonTg) genotype. Despite no differences among groups in
total latency to escape the Barnes maze, a greater number of errors were noticed
before entering the target hole in 19-month-old P8/3xTg-AD mice at day 5,
compared to other groups. Postmortem analyses revealed increased cortical levels
of phospho-tau (Thr231) in female P8/3xTg-AD mice (+277% vs. R1/3xTg-AD mice),
without other tau-related changes. Female P8/3xTg-AD mice exhibited higher
cortical soluble Abeta40 and Abeta42 concentrations (Abeta40, +85%; Abeta42, +35%
vs. R1/3xTg-AD), whereas insoluble forms remained unchanged. Higher Abeta42 load
coincided with increased astroglial activation in female P8/3xTg-AD mice, as
measured with glial fibrillary acidic protein (GFAP) (+57% vs. R1/3xTg-AD mice).
To probe neuronal degeneration, concentrations of neuronal nuclei (NeuN) were
measured, but no differences were detected between groups. Altogether, the SAMP8
genotype had deleterious effects on spatial memory and exerted female-specific
aggravation of AD neuropathology without overt neurodegeneration in 3xTg-AD mice.
PMID- 29341273
TI - Editorial: getting bullish about portal hypertension-chronic treatment with oral
taurine? Author's reply.
PMID- 29341274
TI - Letter: addition of azathioprine to infliximab maintenance therapy in patients
with anti-drug antibodies and subclinical inflammation.
PMID- 29341275
TI - Editorial: vedolizumab as a treatment and cause of extra-intestinal
manifestations of inflammatory bowel disease.
PMID- 29341276
TI - Letter: more studies are needed to elucidate the impact of HBV/HCV coinfection on
cirrhosis and its consequences-Authors' reply.
PMID- 29341277
TI - Editorial: tofacitinib and biologics for moderate-to-severe ulcerative colitis
what is best in class? Authors' reply.
PMID- 29341278
TI - Editorial: direct-acting antivirals significantly improve quality of life in
patients with hepatitis C virus infection-Author's reply.
PMID- 29341279
TI - Letter: more studies are needed to elucidate the impact of HBV/HCV coinfection on
cirrhosis and its consequences.
PMID- 29341280
TI - Editorial: direct-acting antivirals significantly improve quality of life in
patients with hepatitis C virus infection.
PMID- 29341281
TI - Editorial: tofacitinib and biologics for moderate-to-severe ulcerative colitis
what is best in class?
PMID- 29341282
TI - Expression analyses of candidate genes related to meat quality traits in squabs
from two breeds of meat-type pigeon.
AB - In this study, meat quality traits were compared between squabs from two pigeon
breeds: one Chinese indigenous breed, the Shiqi (SQ) meat-type pigeon, and an
imported breed, the white king (WK) meat-type pigeon. Breed differences were
detected in the content of intramuscular fat (IMF) in the breast muscle. SQ
squabs had significantly higher IMF content than the WK birds. The shear force
value (an objective measure of meat tenderness) of SQ birds was also relatively
lower than that of the WK squabs. Further analysis of fatty acids profile
revealed that SQ squabs exhibited significant advantage in the synthesis of
polyunsaturated fatty acids, while WK squabs were significantly higher in the sum
of monounsaturated fatty acids. Breast muscle in the SQ squabs was also
significantly higher in the ratio of polyunsaturated fatty acids to saturated
fatty acids, as well as the sum of omega 6 fatty acids. Variability of expression
levels of functional genes in relation to fat accumulation and meat tenderness
was analysed by qRT-PCR. Gene expression analyses showed that the hepatic
expression of LPL (lipoprotein lipase), FABP4 (fatty acid-binding protein 4), and
CAPN2 (calpain-2) were significantly higher in the SQ squabs. In the breast
muscle tissue, the FABP3 (fatty acid-binding protein 3) and CAPN2mRNA abundance
was significantly higher in SQ squabs. Our results suggested that these
differentially expressed genes might be candidate genes used in the programmes of
targeted selection for squabs with higher IMF content, tender meat, and more
favourable fatty acids composition.
PMID- 29341283
TI - Mogamulizumab-induced photosensitivity in patients with mycosis fungoides and
other T-cell neoplasms.
AB - BACKGROUND: Mogamulizumab (Mog) is a defucosylated, therapeutic monoclonal
antibody, targeting CCR4 and was first approved in Japan for the treatment of
adult T-cell leukaemia/lymphoma (ATLL), followed by cutaneous T-cell lymphoma and
peripheral T-cell lymphoma. OBJECTIVE: To retrospectively investigate development
of photosensitivity in patients with mycosis fungoides and other T-cell neoplasms
after treatment with Mog. METHODS: We treated seven cutaneous lymphoma patients
with Mog. Upon combination treatment with narrow-band UVB, we noticed that four
patients developed photosensitivity dermatitis following Mog therapy, including
two cases of mycosis fungoides, one case of adult T-cell leukaemia/lymphoma and
one case of EB virus-associated T-cell lymphoproliferative disorder. Phototest
was performed with UVA and UVB, and immunohistochemical staining for CD4, CD8 and
Foxp3 was conducted in both photosensitivity and lymphoma lesions. RESULTS:
Phototest revealed that the action spectrum of the photosensitivity was UVB in
three cases and both UVB and UVA in one case. Histopathologically, the
photosensitive lesions were characterized by a lichenoid tissue reaction with a
CD8+ T cell-dominant infiltrate, sharing the feature with chronic actinic
dermatitis, an autoreactive photodermatosis with a cytotoxic T-cell response.
Foxp3+ regulatory T cells (Tregs) were decreased in the photosensitivity lesions
compared with the lymphoma lesions. CONCLUSION: Increased incidence of
photosensitivity reaction was observed during Mog treatment. Decreased number of
Tregs in the lesional skin suggests that this reaction is possibly induced by
autoreactive cytotoxic T cells.
PMID- 29341284
TI - Atypical presentation of eosinophilic annular erythema in a 5-year-old girl.
PMID- 29341285
TI - 2,2'-Bipyridine Equipped with a Disulfide/Dithiol Switch for Coupled Two-Electron
and Two-Proton Transfer.
AB - [1,2]Dithiino[4,3-b:5,6-b']dipyridine (1) and its protonated open form 3,3'
dithiol-2,2'-bipyridine (2) were synthesised and their interconversion
investigated. The X-ray structure of 2 revealed an anti orientation of the two
pyridine units and a zwitterionic form. In depth electrochemical studies in
combination with DFT calculations lead to a comprehensive picture of the redox
chemistry of 1 in the absence and presence of protons. Initial one-electron
reduction at E1 =-1.20 V results in the formation of the radical anion 1red with
much elongated S-S bond, which readily undergoes further reduction at E2 =-1.38
V. Water triggers a potential inversion (E>=-1.13 V for the second reduction) as
the radical anion 1red is protonated at its basic N atom. DFT studies revealed
that S-S bond breaking and twisting of the pyridine units generally occurs after
the second reduction step, whereas the potential inversion induced by protonation
is a result of charge compensation. The CV data were simulated to derive rate
constants for the individual chemical and electrochemical reactions for both
scenarios in the absence and presence of protons.
PMID- 29341286
TI - Test-1 analyzer and conventional Westergren method for erythrocyte sedimentation
rate: A comparative study between two laboratories.
AB - BACKGROUND: Measurement of the length of sedimentation reaction in blood (LSRB),
also called erythrocyte sedimentation rate (ESR), is a widely used hematology
test. This study intends to compare ESR levels measured by Test-1 method and
International Council for Standardization in Hematology's (ICSH) reference
method, and analyzes the effect of hematocrit (Hct) on ESR results. MATERIAL AND
METHODS: A total of 755 patients from 2 hospitals were included in the study, and
samples with EDTA were studied by Test-1 method for ESR measurement and total
blood count, whereas citrated samples were studied with reference Westergren
method. Then, 2 methods were compared. Distribution of ESR results according to
the ESR(<=20, >20 mm/h) and Hct(>=35%, <35%) levels and hospital type was
analyzed. ESR levels with Hct levels<35% were corrected with Fabry's formula.
RESULTS: The mean and SD values for the Test-1 method, reference Westergren
method, and corrected ESR measurement were 21.30 +/- 18.39, 28.59 +/- 25.82, and
24.92 +/- 20.58 mm/h, respectively. Within the whole group, the correlation
coefficient (r) was .77 (.7-.80) with a significance level P < .001. Passing
Bablok regression analysis of the methods resulted in a regression equation y =
1.00 (95% Cl: 0.43-1.88) + 0.75 (95% Cl: 0.70-0.78)x while the significance of
linearity was acceptable (P < .01). All subgroup linear regression analyses
revealed that the correlation was acceptable, except ESR > 20 mm/h group, Hct <
35% group, and corrected ESR group (significance level were P > .10). CONCLUSION:
The study showed that the role of the hospital and the capacity of testing are
important in choosing the instrument for measuring ESR. Furthermore, the patient
profile, especially malignancy possibility and Hct level, may be important for
instrument selection.
PMID- 29341287
TI - One-Pot Synthesis of Functionalized Fused Furans via a BODIPY-Catalyzed Domino
Photooxygenation.
AB - Six-membered ring fused furans containing a tetrasubstituted tertiary carbon were
prepared in an unprecedented one-pot BODIPY-catalyzed domino
photooxygenation/reduction process. A series of functionalized furans was
synthesized from readily available 2-alkenylphenols and mechanistic studies were
performed to account for the domino photosensitized oxygenation.
PMID- 29341288
TI - Lipid and Nucleic Acid Chemistries: Combining the Best of Both Worlds to
Construct Advanced Biomaterials.
AB - Hybrid synthetic amphiphilic biomolecules are emerging as promising
supramolecular materials for biomedical and technological applications. Herein,
recent progress in the field of nucleic acid based lipids is highlighted with an
emphasis on their molecular design, synthesis, supramolecular properties,
physicochemical behaviors, and applications in the field of health science and
technology. In the first section, the design and the study of nucleolipids are in
focus and then the glyconucleolipid family is discussed. In the last section,
recent contributions of responsive materials involving nucleolipids and their use
as smart drug delivery systems are discussed. The supramolecular materials
generated by nucleic acid based lipids open new challenges for biomedical
applications, including the fields of medicinal chemistry, biosensors,
biomaterials for tissue engineering, drug delivery, and the decontamination of
nanoparticles.
PMID- 29341289
TI - Medically unexplained dermatologic symptoms: hiding in plain sight?
PMID- 29341290
TI - Early failure of kidney transplants in the current era-a national cohort study.
AB - Although short-term outcome after kidney transplantation has improved, a small
proportion of grafts are lost during the first year. We characterize in detail
all early graft losses in the current era in a nationwide cohort of kidney
transplant recipients. Altogether 2447 kidney transplantations, performed between
June 2004 and October 2016, were included. All graft losses (return to dialysis
or patient death) occurring during the first post-transplant year were
characterized. During the first post-tranplant year, altogether 109 grafts were
lost, 67 grafts failed, and 42 patients died. Fifty-five per cent of the deaths
were due to cardiovascular causes, and 29% due to infectious causes. Twenty-one
per cent of the failed grafts were primary nonfunction of unknown reason, 34%
were lost due to venous thrombosis and 9% due to arterial thrombosis, but only 10
(15%) patients lost a graft due to acute cellular or humoral rejection.
Independent risk factors for death included diabetes, and longer duration of
pretransplant dialysis treatment, whereas risk factors for graft failure included
increased level of panel-reactive antibodies and increased cold ischaemia time.
Kidney allografts are rarely lost due to immunological reasons during the first
post-transplant year. The most common causes of early death after transplantation
are cardiovascular and infectious causes.
PMID- 29341291
TI - Dermoscopy of basal cell carcinoma.
AB - Dermoscopy is widely used in dermatological practice. The method increases the
accuracy of basal cell carcinoma (BCC) detection. Pigmented and nonpigmented
variants of basal cell carcinoma present different dermoscopic features. Specific
dermoscopy criteria have been recognized in different subtypes of BCC.
Differentiation of superficial BCC from other subtypes is the most important
issue, as it may determine further management decisions.
PMID- 29341292
TI - Amniotic fluid stem cell exosomes: Therapeutic perspective.
AB - It is widely accepted that the therapeutic potential of stem cells can be largely
mediated by paracrine factors, also included into exosomes. Thus, stem cell
derived exosomes represent a major therapeutic option in regenerative medicine
avoiding, if compared to stem cells graft, abnormal differentiation and tumor
formation. Exosomes derived from mesenchymal stem cells (MSC) induce damaged
tissue repair, and can also exert immunomodulatory effects on the
differentiation, activation and function of different lymphocytes. Therefore, MSC
exosomes can be considered as a potential treatment for inflammatory diseases and
also an ideal candidate for allogeneic therapy due to their low immunogenicity.
Amniotic fluid stem cells (AFSCs) are broadly multipotent, can be expanded in
culture, and can be easily cryopreserved in cellular banks. In this study,
morphology, phenotype, and protein content of exosomes released into amniotic
fluid in vivo and from AFSC during in vitro culture (conditioned medium) were
examined. We found that AFSC-derived exosomes present different molecules than
amniotic fluid ones, some of them involved in immunomodulation, such transforming
growth factor beta and hepatic growth factors. The immunomodulatory effect of
AFSC's exosomes on peripheral blood mononuclear cells stimulated with
phytohemagglutinin was compared to that of the supernatant produced by such
conditioned media deprived of exosomes. We present evidence that the principal
effect of AFSC conditioned media (without exosomes) is the induction of apoptosis
in lymphocytes, whereas exposure to AFSC-derived exosomes decreases the
lymphocyte's proliferation, supporting the hypothesis that the entire secretome
of stem cells differently affects immune-response. (c) 2017 BioFactors, 44(2):158
167, 2018.
PMID- 29341293
TI - Circularly Polarized Luminescence from Inorganic Materials: Encapsulating Guest
Lanthanide Oxides in Chiral Silica Hosts.
AB - Recently, circularly polarized luminescence (CPL)-active systems have become a
very hot and interesting subject in chirality- and optics-related areas. The CPL
active systems are usually available by two approaches: covalently combining a
luminescent centre to chiral motif or associating the guest of luminescent probe
to a chiral host. However, all the chiral components in CPL materials were
organic, although the luminescent components were alternatively organics or
inorganics. Herein, the first totally inorganic CPL-active system by "luminescent
guest-chiral host" strategy is proposed. Luminescent sub-10 nm lanthanide oxides
(Eu2 O3 or Tb2 O3 ) nanoparticles (guests) were encapsulated into chiral non
helical SiO2 nanofibres (host) through calcination of chiral SiO2 hybrid
nanofibres, trapping Eu3+ (or Tb3+ ). These lanthanide oxides display circular
dichroism (CD) optical activity in the ultraviolet wavelength and CPL signals
around at 615 nm for Eu3+ and 545 nm for Tb3+ . This work has implications for
inorganic-based CPL-active systems by incorporation of various luminescent guests
within chiral inorganic hosts.
PMID- 29341294
TI - Topical nitroglycerin for the treatment of intraoperative microsurgical
vasospasm.
AB - BACKGROUND: Papaverine remains a popular agent to treat intraoperative
microsurgical vasospasm. However, the recent shortage has forced surgeons to
trial antispasmodic agents unproven in microsurgery, but commonly used in other
areas. During this shortage we have trialed topical nitroglycerin to break
intraoperative vasospasm. This study aims to analyze the outcomes of this
medication on flap complications compared with papaverine. METHODS: All
consecutive free flaps performed for breast reconstruction at a single
institution were reviewed. Data collected included patient demographics, co
morbidities, complications and type of antispasmodic agent. Rates of re
exploration, complications and flap salvage were compared between patients
receiving nitroglycerin and papaverine. RESULTS: Over 10 years, 991 flaps were
treated with antispasmodics: 18 of which were treated with topical nitroglycerin.
Patients treated with nitroglycerin tended to have higher BMI (32.1 vs. 27.9, P <
0.01), higher rates of pre-operative chemotherapy (83.3% vs. 51.3%, P < 0.01) and
shorter follow-up duration (735 vs. 1691 days, P < 0.01). However, no differences
in complications were observed, including: unplanned return to the operating
room, flap loss, fat necrosis, infection, hematoma, or seroma. Subgroup analysis
with a time-matched cohort of papaverine patients revealed minimal difference in
comorbidities and no difference in complications. CONCLUSIONS: Substituting
topical nitroglycerin for papaverine to treat vasospasm during the shortage did
not demonstrate an increased rate of flap loss or return to the operating room,
making these medications a safe alternative to papaverine.
PMID- 29341295
TI - Sustainability of the Australian radiation oncology workforce: A survey of
radiation therapists and radiation oncology medical physicists.
AB - This study aimed to determine and compare Radiation Therapists' (RTs') and
Radiation Oncology Medical Physicists' (ROMPs') perspectives about their
profession and workplace, satisfaction with career progression opportunities, and
leaving the current workplace. RTs and ROMPs who were currently or had previously
worked in Australia were invited to complete an online survey. Univariate and
multivariate methods were used for analysis. Participants were 342 RTs and 112
ROMPs with estimated response rates of 14% and 26% respectively. Both professions
rated workload poorly and identified the need for improvement in: communication
between professions' members, support for junior staff/new graduates, staff
morale, on-site training and multidisciplinary communication. RTs, more than
ROMPs, perceived their profession was recognised and respected, but RTs were less
likely to be satisfied with career progression/advancement, job promotion
prospects and opportunities to specialise. At least 20% of RTs and ROMPs were
thinking about leaving their workplace and 13% of RTs and 8% of ROMPs were
thinking about leaving their profession. Different factors contributed to
workforce satisfaction and retention within each profession. Staff satisfaction
and career progression are critical to retain RTs and ROMPs. Further research is
required to explore strategies to address workplace dissatisfaction, recruitment
and retention.
PMID- 29341296
TI - The five-year survival of children with Down syndrome in Norway 1994-2009
differed by associated congenital heart defects and extracardiac malformations.
AB - AIM: We investigated the prevalence of Down syndrome in a nationwide birth
cohort, focusing on congenital heart defects (CHDs), their associations with
extracardiac malformations (ECM) and survival. METHODS: National registers were
used to identify Norwegian births (1994-2009) and deaths (1994-2014) and updated
with hospital diagnoses. We estimated birth defect frequencies in Down syndrome
and the general population, the association between CHDs and ECM and hazard
ratios for death from different combinations of CHDs and ECM. RESULTS: Down
syndrome was found in 1672 of 953 450 births (17.6 per 10 000). Of the 1251 live
births (13.3 per 10 000), 58% had CHD and 9% ECM. CHDs were associated with
oesophageal atresia (p = 0.02) and Hirschsprung's disease (p = 0.03) but with no
other malformations. The five-year survival for Down syndrome increased from
91.8% (1994-1999) to 95.8% (2000-2009) (p = 0.006), and overall survival was
92.0% with CHD and 97.4% without. Compared with Down syndrome children without
CHD or ECM, the five-year mortality was similar for those with nonsevere CHDs,
without or with ECM, but 4-7 times higher in those with severe CHDs without ECM
and 13-28 times higher in those with severe CHDs and ECM. CONCLUSION: Down
syndrome childhood survival improved, but mortality remained high with severe
CHDs and extracardiac defects.
PMID- 29341297
TI - Ligand- and Metal-Based Reactivity of a Neutral Ruthenium Diolefin Diazadiene
Complex: The Innocent, the Guilty and the Suspicious.
AB - Coordination of the diazadiene diolefin ligand (trop2 dad) to ruthenium leads to
various complexes of composition [Ru(trop2 dad)(L)]. DFT studies indicate that
the closed-shell singlet (CSS), open-shell singlet (OSS), and triplet electronic
structures of this species are close in energy, with the OSS spin configuration
being the lowest in energy for all tested functionals. Singlet-state CASSCF
calculations revealed a significant multireference character for these complexes.
The closed-shell singlet wavefunction dominates, but these complexes have a
significant (~8-16 %) open-shell singlet [d7 -RuI (L)(trop2 dad.- )] contribution
mixed into the ground state. In agreement with their ambivalent electronic
structure, these complexes reveal both metal- and ligand-centered reactivity.
Most notable are the reactions with AdN3 , diazomethane, and a phosphaalkyne
leading to scission of the C-C bond of the diazadiene (dad) moiety of the trop2
dad ligand, resulting in net (formal) nitrene, carbene, or P=C insertion in the
dad C-C bond, respectively. Supporting DFT studies revealed that several of the
ligand-based reactions proceed via low-barrier radical-type pathways, involving
the dad.- ligand radical character of the OSS or triplet species.
PMID- 29341298
TI - Multiple signaling systems target a core set of transition metal homeostasis
genes using similar binding motifs.
AB - Bacterial response to metals can require complex regulation. We report an
overlapping regulation for copper and zinc resistance genes in the denitrifying
bacterium, Pseudomonas stutzeri RCH2, by three two-component regulatory proteins
CopR1, CopR2 and CzcR. We conducted genome-wide evaluations to identify gene
targets of two paralogous regulators, CopR1 and CopR2, annotated for copper
signaling, and compared the results with the gene targets for CzcR, implicated in
zinc signaling. We discovered that the CopRs and CzcR have largely common
targets, and crossregulate a core set of P. stutzeri copper and zinc responsive
genes. We established that this crossregulation is enabled by a conserved binding
motif in the upstream regulatory regions of the target genes. The crossregulation
is physiologically relevant as these regulators synergistically and
antagonistically target multicopper oxidases, metal efflux and sequestration
systems. CopR1 and CopR2 upregulate two cop operons encoding copper tolerance
genes, while all three regulators downregulate a putative copper chaperone,
Psest_1595. CzcR also upregulated the oprD gene and the CzcIABC Zn2+ efflux
system, while CopR1 and CopR2 downregulated these genes. Our study suggests that
crossregulation of copper and zinc homeostasis can be advantageous, and in P.
stutzeri this is enabled by shared binding motifs for multiple response
regulators.
PMID- 29341299
TI - Autonomous Purkinje cell axonal dystrophy causes ataxia in peroxisomal
multifunctional protein-2 deficiency.
AB - Peroxisomes play a crucial role in normal neurodevelopment and in the maintenance
of the adult brain. This depends largely on intact peroxisomal beta-oxidation
given the similarities in pathologies between peroxisome biogenesis disorders and
deficiency of multifunctional protein-2 (MFP2), the central enzyme of this
pathway. Recently, adult patients diagnosed with cerebellar ataxia were shown to
have mild mutations in the MFP2 gene, hydroxy-steroid dehydrogenase (17 beta)
type 4 (HSD17B4). Cerebellar atrophy also develops in MFP2 deficient mice but the
cellular origin of the degeneration is unexplored. In order to investigate
whether peroxisomal beta-oxidation is essential within Purkinje cells, the sole
output neurons of the cerebellum, we generated and characterized a mouse model
with Purkinje cell selective deletion of the MFP2 gene. We show that selective
loss of MFP2 from mature cerebellar Purkinje neurons causes a late-onset motor
phenotype and progressive Purkinje cell degeneration, thereby mimicking ataxia
and cerebellar deterioration in patients with mild HSD17B4 mutations. We
demonstrate that swellings on Purkinje cell axons coincide with ataxic behavior
and precede neurodegeneration. Loss of Purkinje cells occurs in a characteristic
banded pattern, proceeds in an anterior to posterior fashion and is accompanied
by progressive astro- and microgliosis. These data prove that the peroxisomal
beta-oxidation pathway is required within Purkinje neurons to maintain their
axonal integrity, independent of glial dysfunction.
PMID- 29341301
TI - Editorial.
PMID- 29341300
TI - Inflammatory and related biomarkers are associated with post-transplant diabetes
mellitus in kidney recipients: a retrospective study.
AB - In this study, we investigate the association between selected inflammatory
related biomarkers and post-transplant hyperglycemia in kidney transplant
recipients. This retrospective analysis comprises 852 patients receiving a kidney
transplant at the Norwegian national transplant center between 2007 and 2012, all
having a normal oral glucose tolerance test (OGTT) before transplantation. A
diagnostic OGTT was performed 10 weeks post-transplant to examine the association
between inflammation-related biomarkers and two-hour plasma glucose (2HPG) by
multivariable linear regression models adjusting for BMI, age, graft function,
fasting insulin levels, dosage of prednisolone, and concentration of calcineurin
inhibitors. Six of 20 biomarkers were significantly associated with 2HPG in
multivariate analyses showing strong associations with soluble tumor necrosis
factor type 1 (P = 0.027), Pentraxin 3 (P = 0.019), macrophage migration
inhibitory factor (P = 0.024), and endothelial protein C receptor (P = 0.001).
These associated markers reflect several distinct but also overlapping pathways
including activation of tumor necrosis factor, macrophages, and endothelial
cells. The multinomial logistic regression model showed a clear association
between the inflammatory biomarkers and post-transplant diabetes mellitus (PTDM).
The association between a range of inflammation markers and PTDM suggests that
these markers may be target for future studies on pathogenesis and perhaps also
treatment of PTDM.
PMID- 29341302
TI - Twisted Charge-Transfer Antennae for Ultra-Bright Terbium(III) and
Dysprosium(III) Bioprobes.
AB - The design of original twisted charge transfer antennae in which a non-planar
geometry is enforced thanks to one or two bulky ortho-Me substituents allows us
to prepare the corresponding ultra-bright TbIII and DyIII bioprobes. The
brightness of the TbIII derivative compares well with that of the benchmark Tb
Lumi4 complex. The first bio-imaging experiments with a DyIII luminescent
bioprobe are also reported.
PMID- 29341303
TI - Cardiorespiratory fitness is associated with enhanced hippocampal functional
connectivity in healthy young adults.
AB - Consistent associations have been found between higher cardiorespiratory fitness
(CRF) and indices of enhanced brain health and function, including behavioral
measures of cognition as well as neuroimaging indicators such as regional brain
volume. Several studies have reported that higher CRF levels are associated with
a larger hippocampus, yet associations between volume and memory or functional
connectivity metrics remain poorly understood. Using a multi-modal framework, we
hierarchically examine the association between CRF and hippocampal volume and
resting state functional connectivity (rsFC) in younger adults, as well as their
relationship between with memory function. We conducted theoretically-driven
analyses with seeds in the anterior and posterior hippocampus, as well as control
seeds in the caudate nucleus. We tested whether (1) hippocampal connectivity with
prefrontal cortical regions was associated with CRF in an adult sample much
younger than traditionally tested, (2) associations between CRF and rsFC remain
significant after adjusting for volume, and (3) volume and rsFC are related to
memory. We found that higher CRF levels were associated with larger anterior
hippocampal volume and more positive rsFC of the anterior hippocampus to several
regions including the prefrontal cortex. rsFC also accounted for significant
variance in CRF, above and beyond volume. CRF can thus be independently linked to
increased anterior hippocampal volume, as well as stronger hippocampal rsFC in a
population much younger than those typically tested, suggesitng it is critical to
maintainig multiple aspects of brain health.
PMID- 29341304
TI - Enantioselective Synthesis of Aminodiols by Sequential Rhodium-Catalysed
Oxyamination/Kinetic Resolution: Expanding the Substrate Scope of Amidine-Based
Catalysis.
AB - Regio- and stereoselective oxyamination of dienes through a tandem rhodium
catalysed aziridination-nucleophilic opening affords racemic oxazolidinone
derivatives, which undergo a kinetic resolution acylation process with amidine
based catalysts (ABCs) to achieve s values of up to 117. This protocol was
applied to the enantioselective synthesis of sphingosine.
PMID- 29341306
TI - No concession without demand.
PMID- 29341305
TI - Plasmid-Templated Control of DNA-Cyclodextrin Nanoparticle Morphology through
Molecular Vector Design for Effective Gene Delivery.
AB - Engineering self-assembled superstructures through complexation of plasmid DNA
(pDNA) and single-isomer nanometric size macromolecules (molecular nanoparticles)
is a promising strategy for gene delivery. Notably, the functionality and overall
architecture of the vector can be precisely molded at the atomic level by
chemical tailoring, thereby enabling unprecedented opportunities for
structure/self-assembling/pDNA delivery relationship studies. Beyond this notion,
by judiciously preorganizing the functional elements in cyclodextrin (CD)-based
molecular nanoparticles through covalent dimerization, here we demonstrate that
the morphology of the resulting nanocomplexes (CDplexes) can be tuned, from
spherical to ellipsoidal, rod-type, or worm-like nanoparticles, which makes it
possible to gain understanding of their shape-dependent transfection properties.
The experimental findings are in agreement with a shift from chelate to cross
linking interactions on going from primary-face- to secondary-face-linked CD
dimers, the pDNA partner acting as an active payload and as a template. Most
interestingly, the transfection efficiency in different cells was shown to be
differently impacted by modifications of the CDplex morphology, which has led to
the identification of an optimal prototype for tissue-selective DNA delivery to
the spleen in vivo.
PMID- 29341307
TI - Chemical and Enzymatic Strategies for Bacterial and Mammalian Cell Surface
Engineering.
AB - The cell surface serves important functions such as the regulation of cell-cell
and cell-environment interactions. The understanding and manipulation of the cell
surface is important for a wide range of fundamental studies of cellular behavior
and for biotechnological and medical applications. With the rapid advance of
biology, chemistry and materials science, many strategies have been developed for
the functionalization of bacterial and mammalian cell surfaces. Here, we review
the recent development of chemical and enzymatic approaches to cell surface
engineering with particular emphasis on discussing the advantages and limitations
of each of these strategies.
PMID- 29341308
TI - Stiffness regulates the proliferation and osteogenic/odontogenic differentiation
of human dental pulp stem cells via the WNT signalling pathway.
AB - OBJECTIVES: Researches showed that stiffness of the extracellular matrix can
affect the differentiation of many stem cells. Dental pulp stem cells (DPSCs) are
a promising type of adult stem cell. However, we know little about whether and
how the behaviour of DPSCs is influenced by stiffness. MATERIALS AND METHODS: We
carried out a study that cultured DPSCs on tunable elasticity
polydimethylsiloxane substrates to investigate the influence on morphology,
proliferation, osteogenic/odontogenic differentiation and its possible mechanism.
RESULTS: Soft substrates changed the cell morphology and inhibited the
proliferation of DPSCs. Expression of markers related to osteogenic/odontogenic
differentiation was significantly increased as the substrate stiffness increased,
including ALP (alkaline phosphatase), OCN (osteocalcin), OPN (osteopontin), RUNX
2 (runt-related transcription factor-2), BMP-2 (bone morphogenetic protein-2),
DSPP (dentin sialophosphoprotein) and DMP-1 (dentin matrix protein-1). Mechanical
properties promote the function of DPSCs related to the Wnt signalling pathway.
CONCLUSIONS: Our results showed that mechanical factors can regulate the
proliferation and differentiation of DPSCs via the WNT signalling pathway. This
provides theoretical basis to optimize dental or bone tissue regeneration through
increasing stiffness of extracelluar matrix.
PMID- 29341309
TI - Issue Information-Declaration of Helsinki.
PMID- 29341310
TI - Critical appraisal of the oxidative stress pathway in vitiligo: a systematic
review and meta-analysis.
AB - BACKGROUND: The pathogenesis of vitiligo remains a topic of extensive debate.
This is partly due to the moderate efficacy of current treatments. The role of
the oxidative stress pathway in vitiligo is a popular although controversial
research topic. OBJECTIVE: To clarify the role of the oxidative stress pathway in
vitiligo compared to other inflammatory skin disorders and to assess the
therapeutic role of antioxidants. METHODS: We conducted a systematic search of
the existing literature on the aberrancies of the oxidative stress pathway in
vitiligo. Subsequently, the efficacy of both topical and oral antioxidants in
clinical trials was investigated. RESULTS: A deregulated oxidative pathway is
clearly evident with elevated superoxide dismutase, decreased catalase and
increased lipid peroxidation. However, similar results have been obtained in
other inflammatory skin diseases such as psoriasis, atopic dermatitis, lichen
planus and urticaria. This questions the unique role of oxidative stress in the
development of vitiligo. Some isolated successes have been reported with oral
ginkgo biloba, polypodium leucotomos and vitamin C and E preparations, while
other clinical trials have failed to show reproducible results. The use of
topical antioxidants delivers in general no beneficial results. CONCLUSION: The
oxidative pathway is affected in vitiligo, but its unique initiating or
contributory role in the pathogenesis is less evident. Interesting data support
the added value of oral antioxidants in vitiligo although confirmatory studies
are missing.
PMID- 29341311
TI - Decreased thermal sweating of central sudomotor mechanism in African and Korean
men.
AB - OBJECTIVE: Tropical natives sweat less and preserve more body fluid than
temperate natives, tolerating heat stress. However, the mechanisms involved in
such sweating reduction have not been fully elucidated. We examined the sudomotor
responses of men of African (n = 36) and Korean (n = 41) ancestry during hot
water (43 degrees C) leg immersion (central sudomotor response). Correlations
between mean body temperature, basal metabolic rate (BMR), and sweat rate were
also examined. METHODS: All procedures were done in an automated climate chamber.
Local skin temperatures and BMR were measured and mean body temperature was
calculated. Sweating activities which include evaporative loss rate, sweat onset
time, sweat rate, sweat volume, and whole-body sweat loss volume were examined.
RESULTS: In the heat load test, Africans showed lower mean body and local skin
temperatures than Koreans before and after heating. Before and after heating, BMR
declined significantly in Africans, while that of Koreans declined less. Local
sweat onset time increased more in Africans than in Koreans. Local evaporative
loss rate, local sweat volume, local sweat rate, and whole body sweat loss volume
were reduced in Africans compared with Koreans. There were positive associations
of mean body temperature and resting BMR with mean sweat rate. CONCLUSION: In
conclusion, we observed a larger reduction of sudomotor activity in tropical
Africans than in temperate Koreans, which was associated with their lower mean
body temperature and lower resting BMR.
PMID- 29341312
TI - Recurrent terbinafine resistant Trichophyton rubrum infection in a child with
congenital ichthyosis.
AB - Dermatophytosis in children caused by Trichophyton rubrum is preferably treated
with topical or systemic terbinafine. We report the first case of terbinafine
resistance in a child with recurrent T. rubrum dermatophytosis and congenital
ichthyosiform erythroderma.
PMID- 29341313
TI - Synthesis of alpha-l-Fucopyranoside-Presenting Glycoclusters and Investigation of
Their Interaction with Photorhabdus asymbiotica Lectin (PHL).
AB - Photorhabdus asymbiotica is a gram-negative bacterium that is not only as
effective an insect pathogen as other members of the genus, but it also causes
serious diseases in humans. The recently identified lectin PHL from P.
asymbiotica verifiably modulates an immune response of humans and insects, which
supports the idea that the lectin might play an important role in the host
pathogen interaction. Dimeric PHL contains up to seven l-fucose-specific binding
sites per monomer, and in order to target multiple binding sites of PHL, alpha-l
fucoside-containing di-, tri- and tetravalent glycoclusters were synthesized.
Methyl gallate and pentaerythritol were chosen as multivalent scaffolds, and the
fucoclusters were built from the above-mentioned cores by coupling with different
oligoethylene bridges and propargyl alpha-l-fucosides using 1,3-dipolar azide
alkyne cycloaddition. The interaction between fucoside derivates and PHL was
investigated by several biophysical and biological methods, ITC and SPR
measurements, hemagglutination inhibition assay, and an investigation of
bacterial aggregation properties were carried out. Moreover, details of the
interaction between PHL and propargyl alpha-l-fucoside as a monomer unit were
revealed using X-ray crystallography. Besides this, the interaction with
multivalent compounds was studied by NMR techniques. The newly synthesized
multivalent fucoclusters proved to be up to several orders of magnitude better
ligands than the natural ligand, l-fucose.
PMID- 29341314
TI - Chronic sleep reduction in adolescents-clinical cut-off scores for the Chronic
Sleep Reduction Questionnaire (CSRQ).
AB - The Chronic Sleep Reduction Questionnaire is a validated questionnaire that
measures symptoms of prolonged insufficient and/or poor sleep and therefore
accounts for individuals' sleep need and sleep debt. This study extends its
psychometric properties by providing cut-off scores, using a matched sample of
298 healthy adolescents (15.38 +/- 1.63 years, 37.9% male, mean Chronic Sleep
Reduction Questionnaire score: 32.98 +/- 6.51) and 298 adolescents with
insomnia/delayed sleep-wake phase disorder (15.48 +/- 1.62 years; 37.9% male,
mean Chronic Sleep Reduction Questionnaire score: 42.59 +/- 7.06). We found an
area under the curve of 0.84 (95% confidence interval: 0.81-0.87). Cut-off scores
for optimal sensitivity, optimal specificity and based on Youden's criterion are
provided. These cut-off scores are highly relevant for use of the Chronic Sleep
Reduction Questionnaire in future studies and clinical practice.
PMID- 29341315
TI - Use of quantitative real-time PCR to determine viability of Streptococcus equi
subspecies equi in respiratory secretions from horses with strangles.
AB - BACKGROUND: In recent years, molecular approaches have been able to characterise
the viability of equine upper respiratory tract pathogens using absolute
molecular quantitation as well as detection of transcripts for virulence genes.
OBJECTIVES: The objective of this study was to investigate molecular surrogates
for S. equi subspecies equi (S. equi) viability in biological samples from horses
with strangles. STUDY DESIGN: Retrospective cross-sectional study. METHODS: S.
equi culture-positive and culture-negative upper airway secretions were assessed
by qPCR at the genomic (gDNA) and complimentary DNA (cDNA) level for various
target genes (SeM, SEQ2190, eqbE and szpSe). Absolute quantitation was performed
using standard curves, and the results were expressed as number of S. equi target
genes per MUl of gDNA or cDNA. Additionally, the presence or absence of S. equi
gene expression for the various target genes was assessed and compared with the
culture results. RESULTS: While all 21 culture-positive samples tested S.
equiqPCR positive, up to 43.7 and 18.9% of 64 culture-negative samples tested
qPCR positive at the gDNA and cDNA level, respectively. Significant differences
in absolute quantitation for S. equi at the gDNA level were found between culture
positive and culture-negative samples. When absolute quantitation of S. equi
target genes at the gDNA level was assessed with the presence or absence of
transcripts, there was a significantly higher S. equi target gene number in
samples with expression of transcripts compared with samples with no expression
of transcripts. MAIN LIMITATIONS: The lack of standardisation of samples
collected in the field and the delay from sample collection to samples processing
may have negatively affected the cultivability of S. equi and mRNA quality.
CONCLUSIONS: Molecular viability for S. equi can be investigated by determining
absolute quantitation and/or by detecting mRNA for specific target genes.
However, veterinarians have to be cautioned that any qPCR-positive result for S.
equi needs to be taken seriously and trigger biosecurity protocols aimed at
reducing spread.
PMID- 29341316
TI - Deferoxamine promotes mesenchymal stem cell homing in noise-induced injured
cochlea through PI3K/AKT pathway.
AB - OBJECTIVE: Over 5% of the world's population suffers from disabling hearing loss.
Stem cell homing in target tissue is an important aspect of cell-based therapy,
which its augmentation increases cell therapy efficiency. Deferoxamine (DFO) can
induce the Akt activation, and phosphorylation status of AKT (p-AKT) upregulates
CXC chemokine receptor-4 (CXCR4) expression. We examined whether DFO can enhance
mesenchymal stem cells (MSCs) homing in noise-induced damaged cochlea by PI3K/AKT
dependent mechanism. MATERIALS AND METHODS: Mesenchymal stem cells were treated
with DFO. AKT, p-AKT protein and hypoxia inducible factor 1- alpha (HIF-1alpha)
and CXCR4 gene and protein expression was evaluated by RT- PCR and Western blot
analysis. For in vivo assay, rats were assigned to control, sham, noise exposure
groups without any treatment or receiving normal, DFO-treated and DFO +LY294002
(The PI3K inhibitor)-treated MSCs. Following chronic exposure to 115 dB white
noise, MSCs were injected into the rat cochlea through the round window. Number
of Hoechst- labelled cells was determined in the endolymph after 24 hours.
RESULTS: Deferoxamine increased P-AKT, HIF-1alpha and CXCR4 expression in MSCs
compared to non-treated cells. DFO pre-conditioning significantly increased the
homing ability of MSCs into injured ear compared to normal MSCs. These effects of
DFO were blocked by LY294002. CONCLUSIONS: Pre-conditioning of MSCs by DFO before
transplantation can improve stem cell homing in the damaged cochlea through
PI3K/AKT pathway activation.
PMID- 29341317
TI - Apoptosis induction in K562 human myelogenous leukaemia cells is connected to the
modulation of Wnt/beta-catenin signalling by BHX, a novel pyrazoline derivative.
AB - OBJECTIVES: The goal of this study was to explore the effects of BHX on human
chronic myeloid leukaemia (CML) cells and to elucidate the underlying molecular
mechanism. MATERIALS AND METHODS: CML cell line K562 cells were treated with BHX.
The effects of BHX on cell proliferation, apoptosis and cell cycle were detected.
Subsequently, the caspase, ATP activity, Ca2+ , ROS and mitochondrial membrane
potential (MMP) levels treated with various concentrations of BHX were analysed.
The variation of relevant proteins and genes was detected. Further, toxicity of
BHX on peripheral blood cells, bone marrow-nucleated cells (BMNC) and organ index
were investigated on mice. RESULTS: Results showed that BHX suppressed K562 cell
proliferation in a dose-dependent manner and induced apoptosis and G0/G1 phase
arrest. BHX induced mitochondria-mediated apoptosis, which was associated with
downregulation of MMP, activation of caspase-3 and caspase-9, generation of
intracellular ROS and elevation of Ca2+ in K562 cells. In treated cells, ATP
levels were decreased, expression of total beta-catenin, phosphorylated beta
catenin and beta-catenin in the nucleus was decreased, and expression of cell
cycle-related proteins was decreased. Further analysis revealed that BHX lowered
the transcriptional level of beta-catenin. Lastly, BHX treatment significantly
reduced the number of white blood cells, but had no effect on BMNC and organ
index. CONCLUSIONS: These findings provide further insight into the potential use
of BHX as an anti-cancer agent against human leukaemia.
PMID- 29341318
TI - Cognitive trajectories and spectrum of neuropathology in SuperAgers: The first 10
cases.
AB - On average, memory capacity is significantly higher in populations of 50-60 year
olds than in populations of 80 year olds. We define SuperAgers as individuals 80
or older whose episodic memory capacity is at least as good as that of
cognitively average individuals in their 50s and 60s. SuperAgers therefore have
memory capacity that is superior for age. Previous work showed that SuperAgers
have greater cortical volumes and greater resistance to age-related cortical
atrophy than "cognitively average" individuals of the same age. Here we report on
the cognitive, personality, and neuropathologic characteristics of the first 10
autopsy cases in the Northwestern SuperAging Program. During the follow-up
period, seven SuperAgers maintained episodic memory performance within or above
the average range for 50-65 year-old norms and all 10 SuperAgers maintained
episodic memory scores within normal limits for their own age. Openness to
experience scores tended to be high on the NEO-PI-R measure of personality. The
10 autopsy specimens showed variable findings within the spectrum of Alzheimer
pathology. The hippocampus and entorhinal cortex contained neurofibrillary
degeneration mostly in the Braak II-III stages. However, even these limbic areas
contained many healthy appearing neurons and the neocortex was generally free of
neurofibrillary degeneration. In contrast, neocortical areas in at least five of
the cases contained moderate to high densities of neuritic plaques. These
findings need to be placed in context by comparing them to the neuropathology of
cognitively average individuals of the same age. Future research on SuperAgers is
likely to offer insights into factors that either prevent the emergence of
involutional changes in the brain or that makes cognitive function more resistant
to their consequences.
PMID- 29341319
TI - Crosslinking of Semiaromatic Polyesters toward High-Temperature Shape Memory
Polymers with Full Recovery.
AB - In this work, high-temperature shape memory polymers are realized by end-group
crosslinking of the semiaromatic polyesters polyethylene terephthalate as well as
polybutylene terephthalate. Both networks exhibit trigger temperatures distinctly
higher than 200 degrees C and excellent shape memory properties such as storable
strains of 200%, full fixity of the applied strain in the temporary shape, and
full recovery of the permanent shape.
PMID- 29341320
TI - Spatiotemporal, metabolic, and therapeutic characterization of altered functional
connectivity in major depressive disorder.
AB - Although imbalanced functional integration has been increasingly reported in
major depressive disorder (MDD), there still lacks a general framework to
characterize common characteristic and origin shared by the integrative
disturbances. Here we examined spatial selectivity, temporal uniqueness,
metabolic basis, and therapeutic response of altered functional connectivity (FC)
in MDD by analyzing both cross-sectional and longitudinal multimodal functional
magnetic resonance imaging data from 35 patients and 34 demographically matched
healthy controls. First, based on a voxel-wise, data-driven, graph-based degree
centrality approach, the bilateral anterior cingulate gyri, middle frontal gyri
and superior frontal gyri, and the right parahippocampal gyrus were robustly
identified to show decreased FC in MDD. Further spatiotemporal analyses revealed
that these regions exhibited hub-like features and were selectively located in
limbic and default mode networks spatially and, relative to other areas in the
brain, exhibited unique, frequency-dependent oscillation power (stronger within
0.01-0.027 Hz and weaker within 0.027-0.073 Hz) and less dynamical variability of
whole-brain FC profiles temporally. Moreover, a cross-modality fusion analysis
showed that all MDD-related FC impairments were associated with reduced cerebral
blood flow (CBF); however, there existed multiple regions that showed reduced CBF
but had intact FC in the patients, which resulted in a decreased FC-CBF coupling
and implied an earlier emergence of reduced CBF than impaired FC in MDD. Finally,
the disrupted FC in MDD gradually recovered over the course of drug treatment (2
and 12 weeks). Altogether, these findings could help establish a general
framework to provide mechanistic insights into integrative dysfunctions in MDD.
PMID- 29341321
TI - Interleukin-6 contributes to chemoresistance in MDA-MB-231 cells via targeting
HIF-1alpha.
AB - Chemoresistance is a critical challenge in the clinical treatment of triple
negative breast cancer (TNBC). It has been well documented that inflammatory
mediators from tumor microenvironment are involved in the pathogenesis of TNBC
and might be related to chemoresistance of cancer cells. In this study, the
contribution of interleukin-6 (IL-6), one of the principal oncogenic molecules,
in chemoresistance of a TNBC cell line MDA-MB-231 was first investigated. The
results showed that IL-6 treatment could induce upregulation of HIF-1alpha via
the activation of STAT3 in MDA-MB-231 cells, which consequently contributed to
its effect against chemotherapeutic drug-induced cytotoxicity and cell apoptosis.
However, knockdown of HIF-1alpha attenuated such effect via affecting the
expressions of apoptosis-related molecules as Bax and Bcl-2 and drug transporters
as P-gp and MRP1. This study indicated that targeting at IL-6/HIF-1alpha
signaling pathway might be an effective strategy to overcome chemoresistance in
TNBC therapy.
PMID- 29341322
TI - Isthmus sites identified by Ripple Mapping are usually anatomically stable: A
novel method to guide atrial substrate ablation?
AB - BACKGROUND: Postablation reentrant ATs depend upon conducting isthmuses bordered
by scar. Bipolar voltage maps highlight scar as sites of low voltage, but the
voltage amplitude of an electrogram depends upon the myocardial activation
sequence. Furthermore, a voltage threshold that defines atrial scar is unknown.
We used Ripple Mapping (RM) to test whether these isthmuses were anatomically
fixed between different activation vectors and atrial rates. METHODS: We studied
post-AF ablation ATs where >1 rhythm was mapped. Multipolar catheters were used
with CARTO Confidense for high-density mapping. RM visualized the pattern of
activation, and the voltage threshold below which no activation was seen.
Isthmuses were characterized at this threshold between maps for each patient.
RESULTS: Ten patients were studied (Map 1 was AT1; Map 2: sinus 1/10, LA paced
2/10, AT2 with reverse CS activation 3/10; AT2 CL difference 50 +/- 30 ms). Point
density was similar between maps (Map 1: 2,589 +/- 1,330; Map 2: 2,214 +/- 1,384;
P = 0.31). RM activation threshold was 0.16 +/- 0.08 mV. Thirty-one isthmuses
were identified in Map 1 (median 3 per map; width 27 +/- 15 mm; 7 anterior; 6
roof; 8 mitral; 9 septal; 1 posterior). Importantly, 7 of 31 (23%) isthmuses were
unexpectedly identified within regions without prior ablation. AT1 was treated
following ablation of 11/31 (35%) isthmuses. Of the remaining 20 isthmuses, 14 of
16 isthmuses (88%) were consistent between the two maps (four were inadequately
mapped). Wavefront collision caused variation in low voltage distribution in 2 of
16 (12%). CONCLUSIONS: The distribution of isthmuses and nonconducting tissue
within the ablated left atrium, as defined by RM, appear concordant between
rhythms. This could guide a substrate ablative approach.
PMID- 29341323
TI - Test-retest reliability and longitudinal analysis of automated hippocampal
subregion volumes in healthy ageing and Alzheimer's disease populations.
AB - The hippocampal formation is a complex brain structure that is important in
cognitive processes such as memory, mood, reward processing and other executive
functions. Histological and neuroimaging studies have implicated the hippocampal
region in neuropsychiatric disorders as well as in neurodegenerative diseases.
This highly plastic limbic region is made up of several subregions that are
believed to have different functional roles. Therefore, there is a growing
interest in imaging the subregions of the hippocampal formation rather than
modelling the hippocampus as a homogenous structure, driving the development of
new automated analysis tools. Consequently, there is a pressing need to
understand the stability of the measures derived from these new techniques. In
this study, an automated hippocampal subregion segmentation pipeline, released as
a developmental version of Freesurfer (v6.0), was applied to T1-weighted magnetic
resonance imaging (MRI) scans of 22 healthy older participants, scanned on 3
separate occasions and a separate longitudinal dataset of 40 Alzheimer's disease
(AD) patients. Test-retest reliability of hippocampal subregion volumes was
assessed using the intra-class correlation coefficient (ICC), percentage volume
difference and percentage volume overlap (Dice). Sensitivity of the regional
estimates to longitudinal change was estimated using linear mixed effects (LME)
modelling. The results show that out of the 24 hippocampal subregions, 20 had ICC
scores of 0.9 or higher in both samples; these regions include the molecular
layer, granule cell layer of the dentate gyrus, CA1, CA3 and the subiculum (ICC >
0.9), whilst the hippocampal fissure and fimbria had lower ICC scores (0.73
0.88). Furthermore, LME analysis of the independent AD dataset demonstrated
sensitivity to group and individual differences in the rate of volume change over
time in several hippocampal subregions (CA1, molecular layer, CA3, hippocampal
tail, fissure and presubiculum). These results indicate that this automated
segmentation method provides a robust method with which to measure hippocampal
subregions, and may be useful in tracking disease progression and measuring the
effects of pharmacological intervention.
PMID- 29341324
TI - Beta testing the potential link between the alpha antagonist tamsulosin and
dementia.
PMID- 29341325
TI - Characterization of Adrenal Lesions on Unenhanced MRI Using Texture Analysis: A
Machine-Learning Approach.
AB - BACKGROUND: Adrenal adenomas (AA) are the most common benign adrenal lesions,
often characterized based on intralesional fat content as either lipid-rich (LRA)
or lipid-poor (LPA). The differentiation of AA, particularly LPA, from nonadenoma
adrenal lesions (NAL) may be challenging. Texture analysis (TA) can extract
quantitative parameters from MR images. Machine learning is a technique for
recognizing patterns that can be applied to medical images by identifying the
best combination of TA features to create a predictive model for the diagnosis of
interest. PURPOSE/HYPOTHESIS: To assess the diagnostic efficacy of TA-derived
parameters extracted from MR images in characterizing LRA, LPA, and NAL using a
machine-learning approach. STUDY TYPE: Retrospective, observational study.
POPULATION/SUBJECTS/PHANTOM/SPECIMEN/ANIMAL MODEL: Sixty MR examinations,
including 20 LRA, 20 LPA, and 20 NAL. FIELD STRENGTH/SEQUENCE: Unenhanced T1
weighted in-phase (IP) and out-of-phase (OP) as well as T2 -weighted (T2 -w) MR
images acquired at 3T. ASSESSMENT: Adrenal lesions were manually segmented,
placing a spherical volume of interest on IP, OP, and T2 -w images. Different
selection methods were trained and tested using the J48 machine-learning
classifiers. STATISTICAL TESTS: The feature selection method that obtained the
highest diagnostic performance using the J48 classifier was identified; the
diagnostic performance was also compared with that of a senior radiologist by
means of McNemar's test. RESULTS: A total of 138 TA-derived features were
extracted; among these, four features were selected, extracted from the IP
(Short_Run_High_Gray_Level_Emphasis), OP (Mean_Intensity and
Maximum_3D_Diameter), and T2 -w (Standard_Deviation) images; the J48 classifier
obtained a diagnostic accuracy of 80%. The expert radiologist obtained a
diagnostic accuracy of 73%. McNemar's test did not show significant differences
in terms of diagnostic performance between the J48 classifier and the expert
radiologist. DATA CONCLUSION: Machine learning conducted on MR TA-derived
features is a potential tool to characterize adrenal lesions. LEVEL OF EVIDENCE:
4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.
PMID- 29341326
TI - Elevated leukocyte count in cerebrospinal fluid of patients with chronic
inflammatory demyelinating polyneuropathy.
AB - Cerebrospinal fluid (CSF) examination is often part of the diagnostic work-up of
a patient suspected of having chronic inflammatory demyelinating polyneuropathy
(CIDP). According to the European Federation of Neurological Societies and the
Peripheral Nerve Society (EFNS/PNS) criteria, an elevated protein level without
pleocytosis (leukocytes <10 cells/ul) is supportive of the diagnosis CIDP. It is
unclear how many CSF leukocytes are compatible with the diagnosis CIDP and how
extensive the diagnostic work-up should be in patients with a demyelinating
neuropathy and pleocytosis. We performed a retrospective study at two tertiary
neuromuscular referral clinics and identified 14 out of 273 (6%) patients with
CIDP with elevated CSF leukocytes (>=10 cells/ul). All these patients met the
EFNS/PNS criteria for definite or probable CIDP. Eight patients (57%) presented
with a subacute onset and four patients with an antecedent infection. Most
patients responded well to therapy, and eight patients are currently in
remission. In four patients, lumbar puncture was repeated. A spontaneous decrease
in leukocytes before start of treatment was found in three patients. Our data
indicate that a mild to moderate pleocytosis in CSF does not exclude the
diagnosis of CIDP, especially in patients with a subacute onset of disease.
PMID- 29341329
TI - Violence and child mental health in Brazil: The Itaborai Youth Study methods and
findings.
AB - OBJECTIVES: To demonstrate a study design that could be useful in low-resource
and violent urban settings and to estimate the prevalence of child violence
exposure (at home, community, and school) and child mental health problems in a
low-income medium-size city. METHODS: The Itaborai Youth Study is a Norway-Brazil
collaborative longitudinal study conducted in Itaborai city (n = 1409, 6-15 year
olds). A 3-stage probabilistic sampling plan (random selection of census units,
eligible households, and target child) generated sampling weights that were used
to obtain estimates of population prevalence rates. RESULTS: Study strengths
include previous pilot study and focus groups (testing procedures and
comprehension of questionnaire items), longitudinal design (2 assessment periods
with a mean interval of 12.9 months), high response rate (>80%), use of
standardized instruments, different informants (mother and adolescent), face-to
face interviews to avoid errors due to the high frequency of low-educated
respondents, and information gathered on a variety of potential predictors and
protective factors. Children and adolescents presented relevant levels of
violence exposure and clinical mental health problems. CONCLUSIONS: Prevalence
estimates are probably valid to other Brazilian low-income medium-size cities due
to similarities in terms of precarious living conditions. Described study methods
could be useful in other poor and violent world regions.
PMID- 29341328
TI - Histiocytosis - cutaneous manifestations of hematopoietic neoplasm and non
neoplastic histiocytic proliferations.
AB - Histiocytoses are rare disorders characterized by the accumulation of cells
derived from macrophages, dendritic cells or monocytes in various tissues. There
is a broad spectrum of disease manifestations with some subtypes commonly showing
skin lesions, while in others, the skin is rarely involved. Here, we describe
cutaneous manifestations of histiocytoses belonging to the Langerhans group (L
group), the group of cutaneous and mucocutaneous histiocytoses (C group) and the
group of Rosai-Dorfman disease (RDD) and related histiocytoses (R group)
according to the current classification. Characteristic clinical presentations
noted were a rust-brown colour or xanthomatous aspect in many cases of
histiocytoses. Histological criteria for differentiation are described.
Immunohistochemistry shows positivity for S100 and CD1a in Langerhans-cell
histiocytoses (LHCH) of the L group, while CD68 positivity with S100 and CD1a
negativity are typical in histiocytoses of the C group of cutaneous and
mucocutaneous histiocytoses. RDD in the R group shows positivity for S100 and
CD68, while CD1a is negative. We further review the pathogenesis of LHCH based on
insights on the central role of the mitogen-activated protein (MAPK) kinase
pathway. Common mutations in various histiocytic populations of diverse ontogeny
and at different stages of differentiation may be responsible for the diverse
clinical picture of this neoplastic entity. For histiocytoses of the C group and
R group, a reactive origin is discussed with the exception of the disseminated
form of juvenile xanthogranuloma. We suggest exploring the role of an origin from
skin residing histiocytes for the isolated cutaneous manifestation in some types.
With regard to therapeutic options, skin-directed therapies are the first choice
in limited disease, while systemic chemotherapy has traditionally been used in
extensive disease. In Langerhans-cell histiocytoses and related entities, therapy
by BRAF inhibition has led to a breakthrough especially in patients with an
activation of the MAPK pathway.
PMID- 29341327
TI - Involvement of the dorsal hippocampus in expression and extinction of cocaine
induced conditioned place preference.
AB - A key aspect of substance abuse is that drug taking often occurs in a specific
context. As a consequence, exposure to drug-associated contexts can trigger
cravings and relapse, even after long periods of abstinence. Although many
studies have demonstrated that the hippocampus is critical for developing and
retrieving contextual and spatial memories, comparatively little is known about
the role of the hippocampus in acquiring and inhibiting memories involving
contexts and drugs of abuse. We examined the effects of hippocampal inactivation
on expression of cocaine-induced conditioned place preference (CPP) after initial
acquisition or extinction of CPP in C57BL/6 mice. During acquisition of CPP,
distinct tactile cues were paired with cocaine (20 mg kg-1 , intraperitoneal,
CS+) and different tactile cues were paired with saline (CS-) on alternate days.
Groups differed in whether the CS+ and CS- cues were presented in the same large
space (one-compartment procedure) or distinct small spaces (two-compartment
procedure), as previous findings demonstrate that a two-compartment configuration
facilitates acquisition and attenuates extinction of a cocaine-induced CPP.
Microinjection of the GABAA agonist, muscimol, into the dorsal hippocampus
impaired (1) retrieval of a place preference after acquisition, (2) extinction of
a place preference, and (3) retrieval of extinction. These effects differed
depending on the spatial configuration during acquisition or extinction,
suggesting that the dorsal hippocampus may differentially modulate drug seeking
during retrieval and extinction of CPP.
PMID- 29341330
TI - Real-Time and High-Resolution Bioimaging with Bright Aggregation-Induced Emission
Dots in Short-Wave Infrared Region.
AB - Fluorescence imaging in the spectral region beyond the conventional near-infrared
biological window (700-900 nm) can theoretically afford high resolution and deep
tissue penetration. Although some efforts have been devoted to developing a short
wave infrared (SWIR; 900-1700 nm) imaging modality in the past decade, long
wavelength biomedical imaging is still suboptimal owing to the unsatisfactory
materials properties of SWIR fluorophores. Taking advantage of organic dots based
on an aggregation-induced emission luminogen (AIEgen), herein microscopic
vasculature imaging of brain and tumor is reported in living mice in the SWIR
spectral region. The long-wavelength emission of AIE dots with certain brightness
facilitates resolving brain capillaries with high spatial resolution (~3 um) and
deep penetration (800 um). Owning to the deep penetration depth and real-time
imaging capability, in vivo SWIR microscopic angiography exhibits superior
resolution in monitoring blood-brain barrier damage in mouse brain, and
visualizing enhanced permeability and retention effect in tumor sites.
Furthermore, the AIE dots show good biocompatibility, and no noticeable
abnormalities, inflammations or lesions are observed in the main organs of the
mice. This work will inspire new insights on development of advanced SWIR
techniques for biomedical imaging.
PMID- 29341331
TI - The relationship between thalamic GABA content and resting cortical rhythm in
neuropathic pain.
AB - Recurrent thalamocortical connections are integral to the generation of brain
rhythms and it is thought that the inhibitory action of the thalamic reticular
nucleus is critical in setting these rhythms. Our work and others' has suggested
that chronic pain that develops following nerve injury, that is, neuropathic
pain, results from altered thalamocortical rhythm, although whether this
dysrhythmia is associated with thalamic inhibitory function remains unknown. In
this investigation, we used electroencephalography and magnetic resonance
spectroscopy to investigate cortical power and thalamic GABAergic concentration
in 20 patients with neuropathic pain and 20 pain-free controls. First, we found
thalamocortical dysrhythmia in chronic orofacial neuropathic pain; patients
displayed greater power than controls over the 4-25 Hz frequency range, most
marked in the theta and low alpha bands. Furthermore, sensorimotor cortex
displayed a strong positive correlation between cortical power and pain
intensity. Interestingly, we found no difference in thalamic GABA concentration
between pain subjects and control subjects. However, we demonstrated significant
linear relationships between thalamic GABA concentration and enhanced cortical
power in pain subjects but not controls. Whilst the difference in relationship
between thalamic GABA concentration and resting brain rhythm between chronic pain
and control subjects does not prove a cause and effect link, it is consistent
with a role for thalamic inhibitory neurotransmitter release, possibly from the
thalamic reticular nucleus, in altered brain rhythms in individuals with chronic
neuropathic pain.
PMID- 29341333
TI - Bronsted Base-Catalyzed Umpolung Intramolecular Cyclization of Alkynyl Imines.
AB - A novel "umpolung" intramolecular cyclization of alkynyl imines, in which the
electrophilic imine sp2 -carbon formally serves as a nucleophilic site, was
developed under Bronsted base catalysis. The reaction involves the unprecedented
catalytic generation of alpha-aminoester enolates from alpha-iminoesters via the
1,2-addition of the anion of a secondary phosphite to an imine moiety followed by
the [1,2]-rearrangement of a dialkoxyphosphoryl moiety from carbon to nitrogen,
which is a formal umpolung process, and the intramolecular addition to an alkyne.
This is a rare example of a [1,2]-rearrangement of a dialkoxyphosphoryl moiety
from carbon to nitrogen to generate an alpha-amino carbanion and the first
catalytic carbon-carbon bond forming reaction utilizing the resulting carbanion
as a nucleophile.
PMID- 29341332
TI - Cornea-Derived Mesenchymal Stromal Cells Therapeutically Modulate Macrophage
Immunophenotype and Angiogenic Function.
AB - Macrophages are crucial drivers of inflammatory corneal neovascularization and
thus are potential targets for immunomodulatory therapies. We hypothesized that
therapeutic use of cornea-derived mesenchymal stromal cells (cMSCs) may alter the
function of macrophages. We found that cMSCs can modulate the phenotype and
angiogenic function of macrophages. In vitro, cMSCs induce apoptosis of
macrophages while preferentially promoting a distinct CD14hi CD16hi CD163hi
CD206hi immunophenotype that has significantly reduced angiogenic effects based
on in vitro angiogenesis assays. In vivo, application of cMSCs to murine corneas
after injury leads to reduced macrophage infiltration and higher expression of
CD206 in macrophages. Macrophages cocultured ("educated") by cMSCs express
significantly higher levels of anti-angiogenic and anti-inflammatory factors
compared with control macrophages. In vivo, injured corneas treated with cMSC
educated macrophages demonstrate significantly less neovascularization compared
with corneas treated with control macrophages. Knocking down the expression of
pigment epithelial derived factor (PEDF) in cMSCs significantly abrogates its
modulating effects on macrophages, as shown by the reduced rate of apoptosis,
decreased expression of sFLT-1/PEDF, and increased expression of vascular
endothelial growth factor-A in the cocultured macrophages. Similarly, cMSCs
isolated from PEDF knockout mice are less effective compared with wild-type cMSCs
at inhibiting macrophage infiltration when applied to wild-type corneas after
injury. Overall, these results demonstrate that cMSCs therapeutically suppress
the angiogenic capacity of macrophages and highlight the role of cMSC secreted
PEDF in the modulation of macrophage phenotype and function. Stem Cells
2018;36:775-784.
PMID- 29341334
TI - Incidence and prognostic impact of cytogenetic aberrations in patients with
systemic mastocytosis.
AB - The clinical behavior of systemic mastocytosis (SM) is strongly associated with
activating mutations in KIT (D816V in >80% of cases), with the severity of the
phenotype influenced by additional somatic mutations, for example, in SRSF2,
ASXL1, or RUNX1. Complex molecular profiles are frequently associated with the
presence of an associated hematologic neoplasm (AHN) and an unfavorable clinical
outcome. However, little is known about the incidence and prognostic impact of
cytogenetic aberrations. We analyzed cytogenetic and molecular characteristics of
109 patients (KIT D816V+, n = 102, 94%) with indolent (ISM, n = 26) and advanced
SM (n = 83) with (n = 73, 88%) or without AHN. An aberrant karyotype was
identified in SM-AHN (16/73, 22%) patients only. In patients with an aberrant
karyotype, additional somatic mutations were identified in 12/16 (75%) patients.
Seven of 10 (70%) patients with a poor-risk karyotype, for example, monosomy 7 or
complex karyotype, and 1/6 (17%) patients with a good-risk karyotype progressed
to secondary acute myeloid leukemia (n = 7) or mast cell leukemia (n = 1) within
a median of 40 months (range 2-190, P = .04). In advanced SM, the median overall
survival (OS) of poor-risk karyotype patients was significantly shorter than in
good-risk/normal karyotype patients (4 vs 39 months; hazard ratio 11.7, 95% CI
5.0-27.3; P < .0001). Additionally, the shortened OS in patients with poor-risk
karyotype was independent from the mutation status. In summary, a poor-risk
karyotype is an independent prognostic variable in advanced SM. Cytogenetic and
molecular analyses should be routinely performed in all patients with advanced SM
+/- AHN because these investigations greatly support prognostication and
treatment decisions.
PMID- 29341335
TI - Osteogenic efficacy of BMP-2 mixed with hydrogel and bone substitute in peri
implant dehiscence defects in dogs: 16 weeks of healing.
AB - OBJECTIVES: The objective of this study was to determine the effect of bone
morphogenetic protein-2 (BMP-2) mixed with either polyethylene glycol hydrogel or
synthetic bone substitute (SBS) on new bone formation in peri-implant dehiscence
defects after 16 weeks of healing. MATERIALS AND METHODS: A guided bone
regeneration procedure was performed in box-type peri-implant defects that were
surgically prepared in six beagle dogs. The following four experimental groups
were used (i) control (no graft), (ii) SBS+hydrogel, (iii) SBS+BMP-2/hydrogel and
(iv) BMP-2/SBS+hydrogel. Volumetric analysis using micro-computed tomography and
histomorphometric analysis was performed at 16 weeks post-operatively. RESULTS:
The amount of new bone and the total augmented volume did not differ
significantly between both BMP-treated groups and the SBS+hydrogel group (p >
.05). Likewise, no histometric differences were observed in the values of new
bone area and bone-to-implant contact ratio among the three augmentation groups
(new bone area: 0.06 +/- 0.08, 0.19 +/- 0.20, 0.48 +/- 0.37 and 0.56 +/- 0.60 mm2
[mean +/- standard deviation] in groups 1-4, respectively; bone-to-implant
contact: 9.44 +/- 11.51%, 19.91 +/- 15.19%, 46.31 +/- 29.82% and 42.58 +/- 26.27%
in groups 1-4, respectively). CONCLUSION: The osteogenic efficacy of BMP-2 on the
regeneration of peri-implant bone defects was not detectable after 16 weeks
regardless of the carrier materials.
PMID- 29341336
TI - Identification of perioperative pulmonary aspiration in children using quality
assurance and hospital administrative billing data.
AB - BACKGROUND: Perioperative aspiration is a rare but potentially devastating
complication, occurring in 1-10 per 10 000 anesthetics based on studies of
quality assurance databases. Quality assurance reporting is known to
underestimate the incidence of adverse outcomes, but few large studies use
supplementary data sources. This study aims to identify the incidence of and risk
factors for perioperative aspiration in children using quality assurance data
supplemented by administrative billing records, and to examine the utility of
billing data as a supplementary data source. METHODS: Aspiration events for
children receiving anesthesia at a tertiary care pediatric hospital between 2008
and 2014 were identified using (i) a perioperative quality assurance database and
(ii) hospital administrative billing records with International Classification of
Diseases, Ninth Revision Clinical Modification coded diagnoses of aspiration.
Records were subject to review by pediatric anesthesiologists. Following
identification of all aspiration events, the incidence of perioperative
aspiration was calculated and risk factors were assessed. RESULTS: 47 272
anesthetic cases were evaluated over 7 years. The quality assurance database
identified 20 cases of perioperative aspiration occurring in surgical inpatients,
same-day admissions, and outpatients. Using hospital administrative data (which
excludes outpatients with shorter than a 24-hour stay), 9 cases of perioperative
aspiration were identified of which 6 had not been found through quality
assurance data. Overall, International Classification of Diseases, Ninth Revision
coding demonstrated a positive predictive value of 94.5% for any aspiration
event; however, positive predictive value was <4% for perioperative aspiration. A
total incidence of 5.5 perioperative aspirations per 10 000 (95% CI: 3.7-8.0 per
10 000) anesthetics was found. CONCLUSION: Quality assurance data offer an
efficient way to measure the incidence of rare events, but may underestimate
perioperative complications. International Classification of Diseases, Ninth
Revision codes for aspiration used as a secondary data source were nonspecific
for perioperative aspiration, but when combined with record review yielded a 30%
increase in identified cases of aspiration over quality assurance data alone. The
use of administrative data therefore holds potential for supplementing quality
assurance studies of rare complications.
PMID- 29341337
TI - Endoscopic endonasal approach for sinonasal and anterior skull base malignancies
in the elderly.
AB - BACKGROUND: The purpose of this study was to report the outcomes of endoscopic
transnasal resection for sinonasal and anterior skull-base cancers in elderly
patients. METHODS: A retrospective review was performed. The patients were
divided into 2 groups, <70 years old and >=70 years old and compared by
univariate analysis. Prognostic factors were evaluated with a multivariate
analysis. Survival rates were also calculated. RESULTS: Two hundred three elderly
patients and 397 younger patients were enrolled in this study. The elderly
patients reported lower survival rates than the younger patients. When melanoma
and esthesioneuroblastoma were censored, the disease-specific survival (DSS) and
recurrence-free survival (RFS) were similar. Complication rates were 17.5%
without any statistical significance between the groups. Multivariate analysis
revealed that histology, stage, surgical margins, and surgical approaches were
independent predictors of survival in elderly patients. CONCLUSION: The
endoscopic transnasal approach reported low mortality and morbidity rates also in
geriatric patients, and age itself is not to be considered as a contraindication.
PMID- 29341338
TI - Human teeth biobank: Microbiological analysis of the teeth storage solution.
AB - The cross-infections may occur during handling of dental elements, affecting the
health of dental practitioners and researchers. This study aimed to analyze the
influence of the storage medium temperature on the bacterial contingent of the
human teeth used for research purposes. Thirty human teeth were donated to the
Human Teeth Biobank immediately after extraction. The teeth were cleaned with tap
water and neutral soap. The teeth were randomly distributed according to the
temperature of the storage solution (deionized water): at 4 degrees C
(refrigerator) or at -10 degrees C (freezer) and were stored individually in
sterile vials during 60 days. After this period, a microbiological analysis
(CFU/mL) of the storage solutions was performed and teeth were submitted to SEM
analysis. Data were analyzed by Kruskal-Wallis test followed by Dunn's post-test
(p <= .05). Total aerobic bacteria ranged from 5.8 to 8.4 log10 CFU/mL for
refrigerated solution and from 1.9 to 8.5 log10 CFU/mL for frozen solution. No
statistical differences were found between the storage solutions (p > .05). The
counts of Streptococcus spp., Lactobacillus spp., and Staphylococcus spp. were
similar for both storage solutions (p > .05). SEM analysis showed spiral- and rod
shaped bacteria attached on teeth stored under 4 degrees C, which may suggest
the presence of Treponema spp. and Lactobacillus spp. Similar morphological forms
were found on teeth stored under -10 degrees C. A biofilm organized in honeycomb
like form was found in the frozen teeth. Cocci were eventually found in all the
samples. It was concluded that bacterial growth and survival were not influenced
by the temperature of the teeth storage solution.
PMID- 29341339
TI - Immunomodulation By Therapeutic Mesenchymal Stromal Cells (MSC) Is Triggered
Through Phagocytosis of MSC By Monocytic Cells.
AB - Mesenchymal stem or stromal cells (MSC) are under investigation as a potential
immunotherapy. MSC are usually administered via intravenous infusion, after which
they are trapped in the lungs and die and disappear within a day. The fate of MSC
after their disappearance from the lungs is unknown and it is unclear how MSC
realize their immunomodulatory effects in their short lifespan. We examined
immunological mechanisms determining the fate of infused MSC and the
immunomodulatory response associated with it. Tracking viable and dead human
umbilical cord MSC (ucMSC) in mice using Qtracker beads (contained in viable
cells) and Hoechst33342 (staining all cells) revealed that viable ucMSC were
present in the lungs immediately after infusion. Twenty-four hours later, the
majority of ucMSC were dead and found in the lungs and liver where they were
contained in monocytic cells of predominantly non-classical Ly6Clow phenotype.
Monocytes containing ucMSC were also detected systemically. In vitro experiments
confirmed that human CD14++ /CD16- classical monocytes polarized toward a non
classical CD14++ CD16+ CD206+ phenotype after phagocytosis of ucMSC and expressed
programmed death ligand-1 and IL-10, while TNF-alpha was reduced. ucMSC-primed
monocytes induced Foxp3+ regulatory T cell formation in mixed lymphocyte
reactions. These results demonstrate that infused MSC are rapidly phagocytosed by
monocytes, which subsequently migrate from the lungs to other body sites.
Phagocytosis of ucMSC induces phenotypical and functional changes in monocytes,
which subsequently modulate cells of the adaptive immune system. It can be
concluded that monocytes play a crucial role in mediating, distributing, and
transferring the immunomodulatory effect of MSC. Stem Cells 2018;36:602-615.
PMID- 29341340
TI - Bias from restricting to live births when estimating effects of prescription drug
use on pregnancy complications: A simulation.
AB - PURPOSE: Administrative claim databases are increasingly being used to study the
safety of medication exposures during pregnancy. These studies are restricted to
live births due to a reliance on algorithms for estimating gestational age that
are based on codes associated with live delivery. Conditioning on live birth may
induce selection bias when studying the effect of a drug on a pregnancy
complication if fetal death is a competing risk for the complication or is caused
by the complication. METHODS: We simulated a population of 100,000 pregnancies
and estimated the impact of selection bias on relative estimates for the effect
of antidepressant exposure on the outcome of preeclampsia. We assumed that the
exposure, outcome, and covariates increased the risk of fetal loss. RESULTS: A
downward bias in the risk ratio was consistently observed when conditioning on
live births. When an unmeasured covariate was assumed to be a common cause of
fetal death, antidepressant use, and preeclampsia, the direction of bias varied
depending on the strength of the confounding relationship coupled with the
selection bias. Despite the very low prevalence of stillbirth, the strength of
the relationship between antidepressant use and stillbirth had a substantial
impact on bias. CONCLUSIONS: Conditioning on live birth can be problematic when
studying pregnancy complications. Simple quantitative selection bias analysis in
populations restricted to live births may not fully account for selection bias.
PMID- 29341341
TI - Prediction of activation patterns preceding hallucinations in patients with
schizophrenia using machine learning with structured sparsity.
AB - Despite significant progress in the field, the detection of fMRI signal changes
during hallucinatory events remains difficult and time-consuming. This article
first proposes a machine-learning algorithm to automatically identify resting
state fMRI periods that precede hallucinations versus periods that do not. When
applied to whole-brain fMRI data, state-of-the-art classification methods, such
as support vector machines (SVM), yield dense solutions that are difficult to
interpret. We proposed to extend the existing sparse classification methods by
taking the spatial structure of brain images into account with structured
sparsity using the total variation penalty. Based on this approach, we obtained
reliable classifying performances associated with interpretable predictive
patterns, composed of two clearly identifiable clusters in speech-related brain
regions. The variation in transition-to-hallucination functional patterns not
only from one patient to another but also from one occurrence to the next (e.g.,
also depending on the sensory modalities involved) appeared to be the major
difficulty when developing effective classifiers. Consequently, second, this
article aimed to characterize the variability within the prehallucination
patterns using an extension of principal component analysis with spatial
constraints. The principal components (PCs) and the associated basis patterns
shed light on the intrinsic structures of the variability present in the dataset.
Such results are promising in the scope of innovative fMRI-guided therapy for
drug-resistant hallucinations, such as fMRI-based neurofeedback.
PMID- 29341342
TI - The Pentagonal-Pyramidal Hexamethylbenzene Dication: Many Shades of Coordination
Chemistry at Carbon.
AB - A recent report on the crystal structure of the pentagonal-pyramidal
hexamethylbenzene dication C6 (CH3 )62+ by Malischewski and Seppelt [Angew. Chem.
Int. Ed. 2017, 56, 368] confirmed the structural proposal made in the first
report of this compound in 1973 by Hogeveen and Kwant [Tetrahedron Lett. 1973,
14, 1665]. The widespread attention that this compound quickly gained led us to
reinvestigate its electronic structure. On the basis of intrinsic bond orbital
analysis, effective oxidation state analysis, ring current analysis, and
comparison with well-established coordination complexes, it is demonstrated that
the central carbon atom behaves like a transition metal. The central (apical)
carbon atom, although best described as a highly Lewis-acidic carbon atom
coordinated with an anionic cyclopentadienyl ligand, is also capable of acting as
an electron-pair donor to a formal CH3+ group. The different roles of
coordination chemistry are discussed.
PMID- 29341343
TI - Small heat shock protein B3 (HSPB3) mutation in an axonal Charcot-Marie-Tooth
disease family.
AB - Heat shock protein B3 (HSPB3) gene encodes a small heat-shock protein 27-like
protein which has a high sequence homology with HSPB1. A mutation in the HSPB3
was reported as the putative underlying cause of distal hereditary motor
neuropathy 2C (dHMN2C) in 2010. We identified a heterozygous mutation (c.352T>C,
p.Tyr118His) in the HSPB3 from a Charcot-Marie-Tooth disease type 2 (CMT2) family
by the method of targeted next generation sequencing. The mutation was located in
the well conserved alpha-crystalline domain, and several in silico predictions
indicated a pathogenic effect of the mutation. Clinical and electrophysiological
features of the patients indicated the axonal type of CMT. Clinical symptoms
without sensory involvements were similar between the present family and the
previous family. Mutations in the HSPB1 and HSPB8 genes have been reported to be
relevant with both types of CMT2 and dHMN. Our findings will help in the
molecular diagnosis of CMT2 by expanding the phenotypic range due to the HSPB3
mutations.
PMID- 29341344
TI - The medial temporal lobe functional connectivity patterns associated with forming
different mental representations.
AB - The medial temporal lobes (MTL), and more specifically the hippocampus, are
critical for forming mental representations of past experiences-autobiographical
memories-and for forming other "nonexperienced" types of mental representations,
such as imagined scenarios. How the MTL coordinate with other brain areas to
create these different types of representations is not well understood. To
address this issue, we performed a task-based functional connectivity analysis on
a previously published dataset in which fMRI data were collected as participants
created different types of mental representations under three conditions. One
condition required forming and relating together details from a past event
(autobiographical task), another required forming and relating together details
of a spatial context (spatial task) and another condition required relating
together conceptual/perceptual features of an object (conceptual task). We
contrasted the connectivity patterns associated with a functionally defined
region in the parahippocampal cortex (PHC) and anatomically defined anterior and
posterior hippocampal segments across these tasks. Examining PHC connectivity
patterns revealed that the PHC seed was distinctly connected to other MTL
structures during the autobiographical task, to posterior parietal regions during
the spatial task and to a distributed network of regions for the conceptual task.
Examining hippocampal connectivity patterns revealed that the anterior
hippocampus was preferentially connected to regions of default mode network
during the autobiographical task and to areas implicated in semantic processing
for the conceptual task whereas the posterior hippocampus was preferentially
connected to medial-posterior regions of the brain during the spatial task. We
interpret our findings as evidence that there are MTL-guided networks for forming
distinct types of mental representations that align with functional distinctions
within the hippocampus.
PMID- 29341345
TI - Increase in neutrophils after recombinant tissue plasminogen activator
thrombolysis predicts poor functional outcome of ischaemic stroke: a longitudinal
study.
AB - BACKGROUND AND PURPOSE: Neutrophils, a pivotal immune responder to ischaemic
brain insult, have been involved in neuroplasticity and increase after stroke.
Recombinant tissue plasminogen activator (r-tPA), a promising treatment improving
neuroplasticity, promotes neutrophil degranulation. However, the dynamic profile
of neutrophils after r-tPA treatment and their effect on neurological recovery
after stroke are not well studied. METHODS: Cell counts of neutrophils,
lymphocytes and their ratio (NLR) were measured on admission and 24 h after r-tPA
infusion in 372 consecutively recruited acute ischaemic stroke patients (mean age
64 years). Death or major disability at 3 months after stroke was diagnosed based
on the modified Rankin Scale (mRS >= 3) obtained by neurologists who were blinded
to any hospital records. The longitudinal associations of percentage increase in
neutrophils, lymphocytes and the NLR with death or major disability were examined
by logistic regression adjusting for covariates including neurological deficits
at baseline. RESULTS: Neutrophils exhibited a steeper increase after r-tPA
infusion in patients with death or major disability than in those without (P <
0.001). A 10% increase in neutrophils after r-tPA infusion was associated with an
83% increased risk for death or major disability within 3 months after stroke
onset [odds ratio (OR) 1.99, P = 0.009]. Increased neutrophils at 24 h after r
tPA (OR 6.30, P < 0.001 after log transformation) but not on admission
significantly predicted increased risks for death or major disability within 3
months after stroke onset. A similar phenomenon was also observed for the NLR.
CONCLUSIONS: A dynamic increase in neutrophils after stroke significantly
predicts 3-month death or major disability in acute ischaemic stroke patients
receiving r-tPA treatment.
PMID- 29341346
TI - A systematic review and classification of interventions for speech-sound disorder
in preschool children.
AB - BACKGROUND: Multiple interventions have been developed to address speech sound
disorder (SSD) in children. Many of these have been evaluated but the evidence
for these has not been considered within a model which categorizes types of
intervention. The opportunity to carry out a systematic review of interventions
for SSD arose as part of a larger scale study of interventions for primary speech
and language impairment in preschool children. AIMS: To review systematically the
evidence for interventions for SSD in preschool children and to categorize them
within a classification of interventions for SSD. METHODS & PROCEDURES: Relevant
search terms were used to identify intervention studies published up to 2012,
with the following inclusion criteria: participants were aged between 2 years and
5 years, 11 months; they exhibited speech, language and communication needs; and
a primary outcome measure of speech was used. Studies that met inclusion criteria
were quality appraised using the single case experimental design (SCED) or PEDro
P, depending on their methodology. Those judged to be high quality were
classified according to the primary focus of intervention. OUTCOMES & RESULTS:
The final review included 26 studies. Case series was the most common research
design. Categorization to the classification system for interventions showed that
cognitive-linguistic and production approaches to intervention were the most
frequently reported. The highest graded evidence was for three studies within the
auditory-perceptual and integrated categories. CONCLUSIONS & IMPLICATIONS: The
evidence for intervention for preschool children with SSD is focused on seven out
of 11 subcategories of interventions. Although all the studies included in the
review were good quality as defined by quality appraisal checklists, they mostly
represented lower-graded evidence. Higher-graded studies are needed to understand
clearly the strength of evidence for different interventions.
PMID- 29341347
TI - Employing the arts for knowledge production and translation: Visualizing new
possibilities for women speaking up about safety concerns in maternity.
AB - OBJECTIVES: This project used animated film to translate research findings into
accessible health information aimed at enabling women to speak up and secure
professional help for serious safety concerns during pregnancy and after birth.
We tested as proof of concept our use of the arts both as product (knowledge
production) and process (enabling involvement). BACKGROUND: Emergencies during
pregnancy and birth, while unusual, can develop rapidly and unexpectedly, with
catastrophic consequences. Women's tacit knowledge of changes in their condition
is an important resource to aid early detection, but women can worry about the
legitimacy of their concerns and struggle to get these taken seriously by staff.
DESIGN: Arts-based knowledge translation. A user group of women who had
experienced complications in the perinatal period (n = 34) helped us develop and
pilot test the animation. Obstetricians and midwives (15), clinical leads (3) and
user group representatives (8) helped with the design and testing. FINDINGS: The
consultation process, script and storyboard enabled active interaction with the
evidence, meaningful engagement with stakeholders and new understandings about
securing help for perinatal complications. The method enabled us to address
gender stereotypes and social norms about speaking up and embed a social script
for women within the animation, to help structure their help seeking. While for
some women, there was an emotional burden, the majority were glad to have been
part of the animation's development and felt it had enabled their voices to be
heard. CONCLUSION: This project has demonstrated the benefits of arts-science
collaborations for meaningful co-production and effective translation of research
evidence.
PMID- 29341348
TI - The development and validation of the Evidence-Based Practice Questionnaire:
Japanese version.
AB - AIM: To develop and test the validity and reliability of a Japanese version of
the Evidence-Based Practice Questionnaire. METHODS: The Evidence-Based Practice
Questionnaire was translated into Japanese, and a back-translation was performed.
In March 2016, the survey was conducted among 843 nurses in 2 university
hospitals in Japan. After 2 weeks, the same questionnaire for test-retest
reliability was distributed to 197 nurses. We evaluated construct validity by
factor analysis: convergent, discriminant, criterion-based and known-group
validity, and reliability (internal consistency via Cronbach' alpha and test
retest reliability). RESULTS: A total of 533 (66%) of nurses who agreed to our
study returned the completed questionnaire, and 108 nurses (55%) agreed to the
test-retest. Factor analysis confirmed that the original model of the Evidence
Based Practices Questionnaire was not statistically appropriate for Japanese
nurses. Therefore, the final version of the Japanese version adopted 18 items and
4 subscales including practice, attitudes, and knowledge/skills related to
research and practice. In the final version, the validity and reliability were
moderate (Cronbach alpha = .90). CONCLUSION: The Japanese version of the Evidence
Based Practices Questionnaire is a reliable and valid tool and can be used to
assess evidence-based practice, attitudes, and research knowledge/skills in
Japan.
PMID- 29341349
TI - Peroxiredoxin 4 (PRDX4): Its critical in vivo roles in animal models of metabolic
syndrome ranging from atherosclerosis to nonalcoholic fatty liver disease.
AB - The peroxiredoxin (PRDX) family, a new family of proteins with a pivotal
antioxidative function, is ubiquitously synthesized and abundantly identified in
various organisms. In contrast to the intracellular localization of other family
members (PRDX1/2/3/5/6), PRDX4 is the only known secretory form and protects
against oxidative damage by scavenging reactive oxygen species in both the
intracellular (especially the endoplasmic reticulum) compartments and the
extracellular space. We generated unique human PRDX4 (hPRDX4) transgenic (Tg)
mice on a C57BL/6J background and investigated the critical and diverse
protective roles of PRDX4 against diabetes mellitus, atherosclerosis, insulin
resistance, and nonalcoholic fatty liver disease (NAFLD) as well as evaluated its
role in the intestinal function in various animal models. Our published data have
shown that PRDX4 helps prevent the progression of metabolic syndrome by reducing
local and systemic oxidative stress and synergistically suppressing steatosis,
inflammatory reactions, and/or apoptotic activity. These observations suggest
that Tg mice may be a useful animal model for studying the relevance of oxidative
stress on inflammation and the dysregulation of lipid/bile acid/glucose
metabolism upon the progression of human metabolic syndrome, and that specific
accelerators of PRDX4 may be useful as therapeutic agents for ameliorating
various chronic inflammatory diseases.
PMID- 29341350
TI - The effects of wireless electromagnetic fields on the activities of carbonic
anhydrase and acetylcholinesterase enzymes in various tissues of rats.
AB - The purpose of our study is to assist in understanding the effects of wireless
electromagnetic waves on carbonic anhydrase (CA) and acetylcholinesterase (AChE)
enzymes activities in the different tissues of the rats. For this purpose, two
different groups each of which contains eight rats (n = 8) were formed as being
control group and wireless electromagnetic wave-administered group. The rats were
necropsied after 60 min from the injection of chemicals into the rats
intraperitoneally. The different tissues of the rats were extracted. CA and AChE
enzymes activities were measured for each tissue. All the experimental results
were provided in mean +/- S.D. Statistical significance was identified to be P <
0.05. It was observed that there were significant changes of enzyme activities in
wireless-administered group in salivary gland, stomach, colon, liver, and
striated muscle tissues.
PMID- 29341351
TI - Discordant von Willebrand factor (VWF) activity in patients with VWF p.Gly1324Ser
confirmed in vitro.
PMID- 29341352
TI - Misregulation of membrane trafficking processes in human nonalcoholic
steatohepatitis.
AB - Nonalcoholic steatohepatitis (NASH) remodels the expression and function of genes
and proteins that are critical for drug disposition. This study sought to
determine whether disruption of membrane protein trafficking pathways in human
NASH contributes to altered localization of multidrug resistance-associated
protein 2 (MRP2). A comprehensive immunoblot analysis assessed the
phosphorylation, membrane translocation, and expression of transporter membrane
insertion regulators, including several protein kinases (PK), radixin, MARCKS,
and Rab11. Radixin exhibited a decreased phosphorylation and total expression,
whereas Rab11 had an increased membrane localization. PKCdelta, PKCalpha, and PKA
had increased membrane activation, whereas PKCepsilon had a decreased
phosphorylation and membrane expression. Radixin dephosphorylation may activate
MRP2 membrane retrieval in NASH; however, the activation of Rab11/PKCdelta and
PKA/PKCalpha suggest an activation of membrane insertion pathways as well.
Overall these data suggest an altered regulation of protein trafficking in human
NASH, although other processes may be involved in the regulation of MRP2
localization.
PMID- 29341353
TI - Fluorescence Redox Blinking Adaptable to Structural Analysis of Nucleic Acids.
AB - The phenomenon of blinking is unique to single-molecule fluorescence
measurements. By designing a fluorophore with an appropriate dark-state lifetime
tauoff , a kinetic analysis based on the control of fluorescence blinking (KACB)
was devised to investigate the dynamics of biomolecules. By controlling the redox
reaction-based blinking (rKACB), conformational dynamics of RNA at the single
molecule level was previously investigated. However, there is little knowledge
about suitable fluorescent molecules for rKACB, and the application of rKACB has
been limited to the analysis of hairpins and duplex structures of nucleic acids.
In this work, various fluorescent molecules, including Alexa 488, R6G, TAMRA,
ATTO 647N and ATTO 655, were evaluated for rKACB. Moreover, rKACB was adapted to
the discrimination of DNA/DNA and DNA/RNA nucleic acid duplexes and investigation
of antigen-antibody interactions. By changing the size of the oxidant, it was
possible to determine the solvent accessibility of the target domain of the
analyzed biomolecules.
PMID- 29341354
TI - A mutation in the heptad repeat 2 domain of MFN2 in a large CMT2A family.
AB - Dominant mutations in MFN2 cause a range of phenotypes, including severe, early
onset axonal neuropathy, "classical CMT2," and late-onset axonal neuropathies. We
report a large family with an axonal polyneuropathy, with clinical onset in the
20s, followed by slow progression.
PMID- 29341355
TI - Reflectance confocal microscopy and optical coherence tomography for the
diagnosis of bullous pemphigoid and pemphigus and surrounding subclinical
lesions.
AB - BACKGROUND: Diagnosis of bullous pemphigoid (BP) and pemphigus is based on
clinical features, histology, immunofluorescence and laboratory data. OBJECTIVES:
To evaluate features of BP and pemphigus at reflectance confocal microscopy (RCM)
and optical coherence tomography (OCT) in order to provide a rapid non-invasive
bed-side diagnosis. Secondary objective was to evaluate the detectability of
clinically non-visible lesions. METHODS: This was an observational,
retrospective, multicentre study in which patients with suspicious lesions for BP
or pemphigus underwent clinical assessment, RCM, OCT, blood tests and skin biopsy
for histological and direct immunofluorescence examinations from January 2014 to
December 2015. A total of 72 lesions in 24 selected patients were evaluated.
Additionally, apparently unaffected skin at two different distances [near (1-2
cm) and far (2-3 cm)] from each lesion was examined to test subclinical lesion
detectability. RESULTS: RCM was able to detect subepidermal and intra-epidermal
blisters, respectively, in 75% and 50% of the patients affected by BP and
pemphigus. At OCT, the exact blister level was identified in all patients.
Acantholytic cells were observed only at RCM in pemphigus (62.5%). Fibrin
deposition inside the blisters was only found in BP, evidenced both at RCM and
OCT. Among patients with BP, subclinical blisters were detected in nine (9.4%)
clinically healthy skin, while among patients with pemphigus were observed in 10
(20.8%) apparently unaffected skin. CONCLUSION: RCM and/or OCT provide useful
information for a rapid diagnosis of BP and pemphigus and for the identification
of biopsy site. Combined use of RCM and OCT is optimal because associates the
higher resolution of RCM with the greater penetration depth of OCT. OCT could be
an optimal tool for treatment monitoring, especially in the cases of subclinical
lesions. However, histopathologic and immunologic examinations remain the gold
standard for establishing the final diagnosis.
PMID- 29341356
TI - All over the map: An interobserver agreement study of tumor location based on the
PI-RADSv2 sector map.
AB - BACKGROUND: Prostate imaging reporting and data system version 2 (PI-RADSv2)
recommends a sector map for reporting findings of prostate cancer mulitparametric
MRI (mpMRI). Anecdotally, radiologists may demonstrate inconsistent
reproducibility with this map. PURPOSE: To evaluate interobserver agreement in
defining prostate tumor location on mpMRI using the PI-RADSv2 sector map. STUDY
TYPE: Retrospective. POPULATION: Thirty consecutive patients who underwent mpMRI
between October, 2013 and March, 2015 and who subsequently underwent
prostatectomy with whole-mount processing. FIELD STRENGTH: 3T mpMRI with T2 W,
diffusion-weighted imaging (DWI) (apparent diffusion coefficient [ADC] and b
2000), dynamic contrast-enhanced (DCE). ASSESSMENT: Six radiologists (two high,
two intermediate, and two low experience) from six institutions participated.
Readers were blinded to lesion location and detected up to four lesions as per PI
RADSv2 guidelines. Readers marked the long-axis of lesions, saved screen-shots of
each lesion, and then marked the lesion location on the PI-RADSv2 sector map.
Whole-mount prostatectomy specimens registered to the MRI served as ground truth.
Index lesions were defined as the highest grade lesion or largest lesion if
grades were equivalent. STATISTICAL TEST: Agreement was calculated for the exact,
overlap, and proportion of agreement. RESULTS: Readers detected an average of 1.9
lesions per patient (range 1.6-2.3). 96.3% (335/348) of all lesions for all
readers were scored PI-RADS >=3. Readers defined a median of 2 (range 1-18)
sectors per lesion. Agreement for detecting index lesions by screen shots was
83.7% (76.1%-89.9%) vs. 71.0% (63.1-78.3%) overlap agreement on the PI-RADS
sector map (P < 0.001). Exact agreement for defining sectors of detected index
lesions was only 21.2% (95% confidence interval [CI]: 14.4-27.7%) and rose to
49.0% (42.4-55.3%) when overlap was considered. Agreement on defining the same
level of disease (ie, apex, mid, base) was 61.4% (95% CI 50.2-71.8%). DATA
CONCLUSION: Readers are highly likely to detect the same index lesion on mpMRI,
but exhibit poor reproducibility when attempting to define tumor location on the
PI-RADSv2 sector map. The poor agreement of the PI-RADSv2 sector map raises
concerns its utility in clinical practice. LEVEL OF EVIDENCE: 3 Technical
Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2018;48:482-490.
PMID- 29341357
TI - A multicenter pilot survey to clarify the clinical features of patients with
acute-on-chronic liver failure in Japan.
AB - AIM: To establish diagnostic criteria for acute-on-chronic liver failure (ACLF)
in Japan, a multicenter pilot survey was carried out to examine the usefulness of
overseas criteria in patients with chronic liver diseases manifesting acute
decompensation. METHODS: Patients fulfilling the Asian-Pacific Association for
the Study of the Liver (APASL), European Association for the Study of the Liver
(EASL), or Chinese Medical Association (CMA) criteria for decompensation were
enrolled from eight institutions in Japan, and the clinical features were
evaluated. RESULTS: Among 112 patients, 109 patients (97.3%) fulfilled the APASL
criteria for decompensation; 7 patients were excluded because the decompensation
had been provoked by gastrointestinal bleeding. Consequently, 102 patients
(91.1%) were diagnosed as having ACLF according to the APASL definition. Among
the patients who fulfilled the APASL criteria for decompensation, the etiologies
of the underlying liver diseases were alcohol abuse in 59 cases (54.1%) and
hepatitis B or hepatitis C virus infection in 24 (22.0%). The acute insults were
alcohol abuse in 50 (45.9%), bacterial infection in 26 (23.9%), and exacerbation
of underlying liver disease in 14 (12.8%). Fifty-four patients (49.5%) satisfied
the CMA criteria, but the survival rates were similar between patients who did
and those who did not meet the criteria. When 84 patients with underlying
cirrhosis were classified according to the EASL-Chronic Liver Failure (Clif)
Consortium criteria, the survival rates differed according to grade: 67.6%
(23/34) for patients without ACLF, and 41.2% (14/34) and 18.8% (3/16) for those
with grade 1/2 and grade 3 ACLF, respectively. CONCLUSION: The APASL definition
was suitable for screening Japanese patients with ACLF, including those whose
conditions were triggered by gastrointestinal bleeding, and the EASL-Clif
Consortium criteria were useful for predicting outcome.
PMID- 29341358
TI - Thermal and hydrologic responses to climate change predict marked alterations in
boreal stream invertebrate assemblages.
AB - Air temperature at the northernmost latitudes is predicted to increase steeply
and precipitation to become more variable by the end of the 21st century,
resulting in altered thermal and hydrological regimes. We applied five climate
scenarios to predict the future (2070-2100) benthic macroinvertebrate assemblages
at 239 near-pristine sites across Finland (ca. 1200 km latitudinal span). We used
a multitaxon distribution model with air temperature and modeled daily flow as
predictors. As expected, projected air temperature increased the most in
northernmost Finland. Predicted taxonomic richness also increased the most in
northern Finland, congruent with the predicted northwards shift of many species'
distributions. Compositional changes were predicted to be high even without
changes in richness, suggesting that species replacement may be the main
mechanism causing climate-induced changes in macroinvertebrate assemblages.
Northern streams were predicted to lose much of the seasonality of their flow
regimes, causing potentially marked changes in stream benthic assemblages. Sites
with the highest loss of seasonality were predicted to support future assemblages
that deviate most in compositional similarity from the present-day assemblages.
Macroinvertebrate assemblages were also predicted to change more in headwaters
than in larger streams, as headwaters were particularly sensitive to changes in
flow patterns. Our results emphasize the importance of focusing protection and
mitigation on headwater streams with high-flow seasonality because of their
vulnerability to climate change.
PMID- 29341359
TI - Familiar communication partners' facilitation of topic management in
conversations with individuals with dementia.
AB - BACKGROUND: Language and memory impairments affect everyday interactions between
individuals with dementia and their communication partners. Impaired topic
management, which compromises individuals' construction of relevant, meaningful
discourse, is commonly reported amongst individuals with dementia. Currently,
limited empirical evidence describes the sequential patterns of behaviour
comprising topic-management practices in everyday conversation between
individuals with dementia and their communication partners. AIMS: To describe the
sequential patterns of behaviour relating to the manifestation of topic
management impairments and facilitative behaviours in everyday interactions
between individuals with dementia and their familiar communication partners
(FCPs). METHODS & PROCEDURES: Three 20-min conversations between individuals with
moderate to severe dementia and their FCPs were recorded. Conversation Analysis
was used to examine sequences in which topic-management appeared to be impaired.
OUTCOMES & RESULTS: Conversational behaviours that reflected a difficulty in
contributing on-topic talk were pervasive in the talk of the three individuals
with dementia. FCPs responded to these conversational difficulties by using two
categories of facilitative behaviours. The first involved responding to an
individual with dementia's explicit repair-initiation by performing repair. In
the second category, explicit repair-initiation was absent; instead, the distance
of the conversational difficulty from the prior topic-shifting turn mediated the
form and outcome of the FCPs' facilitative behaviours. Each category successfully
facilitated the individual with dementia to contribute on-topic talk. CONCLUSIONS
& IMPLICATIONS: The findings contribute to a growing understanding of topic
management abilities in everyday interactions involving individuals with
dementia. Individuals with dementia took a proactive role in eliciting topic
management support. The FCPs responded with turns that facilitated the
individuals with dementia to talk on-topic. Clinically, the results support and
extend the current topic-management recommendations available in communication
partner training programmes, and promote conversations which attend to the
personhood of the individual with dementia.
PMID- 29341360
TI - Comparison of respiratory system impedance in asthma and COPD: A prospective
observational study.
AB - BACKGROUND AND OBJECTIVE: A single assessment of within-breath variations of
respiratory system reactance (Xrs) at 5 Hz (DeltaX5) measured by the forced
oscillation technique (FOT) has been reported to be useful for the detection of
pathophysiological changes in chronic obstructive pulmonary disease (COPD) and
asthma. We examined longitudinal changes in respiratory system resistance (Rrs)
and Xrs during tidal breathing between stable asthma and COPD patients in order
to clarify the features of changes of respiratory system impedance and airflow
limitation for these conditions. METHODS: Between April 2013 and September 2013,
outpatients with a COPD or asthma diagnosis were recruited. We examined forced
expiratory volume in 1 s (FEV1 ) and FOT every 6 months until September 2015.
Annual changes were estimated from the linear regression curve slope. RESULTS: We
included 57 and 93 subjects with COPD and asthma, respectively. The median follow
up period was 26 months (range: 24-29 months). Within-breath analysis showed that
the difference between mean Rrs at 5 Hz and 20 Hz was significantly lower, and
DeltaX5 more negative, in COPD than in asthma patients. With regard to annual
changes, only DeltaX5 was significantly different, more negative, in COPD than in
asthma patients. Comparing between COPD subjects of Global Initiative Chronic
Obstructive Lung Disease (GOLD) stage I/II and those with asthma, there were no
significant differences in respiratory system impedance at enrolment, while
annual change in DeltaX5 was significantly more negative in mild COPD than in
asthma patients. CONCLUSION: DeltaX5 may be useful for long-term assessment of
airflow limitation in COPD.
PMID- 29341362
TI - A novel mutation of LRSAM1 in a Chinese family with Charcot-Marie-Tooth disease.
AB - Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral
neuropathy characterized by progressive distal muscle weakness and atrophy with
decreased or absent tendon reflexes. Mutations in LRSAM1 have been identified to
cause CMT disease type 2P. We report a novel LRSAM1 mutation c.2021-2024del
(p.E674VfsX11) in a Chinese autosomal dominant CMT disease type 2 family. The
phenotype was characterized by late onset and mild sensory impairment.
Electrophysiological findings showed normal or mildly to moderately reduced motor
and sensory nerve conduction velocities in lower and upper limb nerves.
PMID- 29341361
TI - Parvalbumin interneuron mediated feedforward inhibition controls signal output in
the deep layers of the perirhinal-entorhinal cortex.
AB - The perirhinal (PER) and lateral entorhinal (LEC) cortex form an anatomical link
between the neocortex and the hippocampus. However, neocortical activity is
transmitted through the PER and LEC to the hippocampus with a low probability,
suggesting the involvement of the inhibitory network. This study explored the
role of interneuron mediated inhibition, activated by electrical stimulation in
the agranular insular cortex (AiP), in the deep layers of the PER and LEC.
Activated synaptic input by AiP stimulation rarely evoked action potentials in
the PER-LEC deep layer excitatory principal neurons, most probably because the
evoked synaptic response consisted of a small excitatory and large inhibitory
conductance. Furthermore, parvalbumin positive (PV) interneurons-a subset of
interneurons projecting onto the axo-somatic region of principal neurons-received
synaptic input earlier than principal neurons, suggesting recruitment of
feedforward inhibition. This synaptic input in PV interneurons evoked varying
trains of action potentials, explaining the fast rising, long lasting synaptic
inhibition received by deep layer principal neurons. Altogether, the excitatory
input from the AiP onto deep layer principal neurons is overruled by strong
feedforward inhibition. PV interneurons, with their fast, extensive stimulus
evoked firing, are able to deliver this fast evoked inhibition in principal
neurons. This indicates an essential role for PV interneurons in the gating
mechanism of the PER-LEC network.
PMID- 29341364
TI - Food-dependent exercise-induced anaphylaxis in Japanese elementary school
children.
AB - BACKGROUND: In 2012, we clarified that the prevalence of food-dependent exercise
induced anaphylaxis (FDEIA) was 0.018% in junior-high students in Yokohama,
Japan. Furthermore, although different from FDEIA, one student who had completed
oral immunotherapy developed anaphylaxis during exercise after eating causative
food. There have been few large-scale epidemiological studies of FDEIA, however,
in elementary school children, therefore we conducted an epidemiological study in
elementary school children in Yokohama to clarify the frequency and
characteristic of FDEIA. METHODS: We sent a questionnaire regarding the
occurrence of FDEIA to all 348 public elementary school nurses in Yokohama. We
also compared the results with those for junior-high school that we previously
reported. We excluded those children with a past history of immediate food
allergy who had achieved desensitization status after oral immunotherapy, from
FDEIA, and instead defined them as having desensitization status and exercise
induced anaphylaxis (DEIA). RESULTS: Of 348 school nurses, 317 responded (91.1%).
Overall, eight of 170 146 children were diagnosed with FDEIA, which was
significantly lower than the prevalence in junior-high school students (0.0047%
vs 0.018%, P = 0.0009). The causative foods were wheat (n = 4), and soy, fruit,
crustaceans, and squid (n = 1 each). Four children had DEIA and the causative
foods were wheat and milk (n = 2 each). Multiple episodes occurred in five
children with FDEIA and in three children with DEIA. CONCLUSIONS: FDEIA was far
less common in elementary school than in junior-high school, and wheat was the
major causative food. The new appearance of DEIA was notable. Decreasing episode
recurrence remains an issue that needs to be resolved.
PMID- 29341365
TI - How and Why Does Helium Permeate Nonporous Arsenolite Under High Pressure?
AB - Investigations into the helium permeation of arsenolite, the cubic, molecular
arsenic(III) oxide polymorph As4 O6 , were carried out to understand how and why
arsenolite helium clathrate As4 O6 ?2 He is formed. High-pressure synchrotron X
ray diffraction experiments on arsenolite single crystals revealed that the
permeation of helium into nonporous arsenolite depends on the time for which the
crystal is subjected to high pressure and on the crystal history. The single
crystal was totally transformed into As4 O6 ?2 He within 45 h under 5 GPa. After
release of the pressure, arsenolite was recovered and a repeated increase in
pressure up to 3 GPa led to practically instant As4 O6 ?2 He formation. However,
when a pristine arsenolite single crystal was quickly subjected to a pressure of
13 GPa, no helium permeation was observed at all. No neon permeation was observed
in analogous experiments. Quantum mechanical computations indicate that there are
no specific attractive interactions between He atoms and As4 O6 molecules at the
distances observed in the As4 O6 ?2 He crystal structure. Detailed analysis of
As4 O6 molecular structure changes has shown that the introduction of He into the
arsenolite crystal lattice significantly reduces molecular deformations by
decreasing the anisotropy of stress exerted on the As4 O6 molecules. This effect
and the pDeltaV term, rather than any specific As???He binding, are the driving
forces for the formation As4 O6 ?2 He.
PMID- 29341366
TI - Impact of multiple stressors on juvenile fish in estuaries of the northeast
Pacific.
AB - A key step in identifying global change impacts on species and ecosystems is to
quantify effects of multiple stressors. To date, the science of global change has
been dominated by regional field studies, experimental manipulation, meta
analyses, conceptual models, reviews, and studies focusing on a single stressor
or species over broad spatial and temporal scales. Here, we provide one of the
first studies for coastal systems examining multiple stressor effects across
broad scales, focused on the nursery function of 20 estuaries spanning 1,600 km
of coastline, 25 years of monitoring, and seven fish and invertebrate species
along the northeast Pacific coast. We hypothesized those species most estuarine
dependent and negatively impacted by human activities would have lower presence
and abundances in estuaries with greater anthropogenic land cover, pollution, and
water flow stress. We found significant negative relationships between juveniles
of two of seven species (Chinook salmon and English sole) and estuarine
stressors. Chinook salmon were less likely to occur and were less abundant in
estuaries with greater pollution stress. They were also less abundant in
estuaries with greater flow stress, although this relationship was marginally
insignificant. English sole were less abundant in estuaries with greater land
cover stress. Together, we provide new empirical evidence that effects of
stressors on two fish species culminate in detectable trends along the northeast
Pacific coast, elevating the need for protection from pollution, land cover, and
flow stressors to their habitats. Lack of response among the other five species
could be related to differing resistance to specific stressors, type and
precision of the stressor metrics, and limitations in catch data across estuaries
and habitats. Acquiring improved measurements of impacts to species will guide
future management actions, and help predict how estuarine nursery functions can
be optimized given anthropogenic stressors and climate change scenarios.
PMID- 29341367
TI - Development of Antibody-Directed Therapies: Quo Vadis?
AB - Less is more: The efficacy of antibody-drug conjugates (ADCs) for cancer therapy
is traditionally associated with cleavable linkers for payload release. Evidence
now suggests that simpler constructs without cleavable moieties can afford more
stable and effective ADCs.
PMID- 29341368
TI - Multiple sclerosis as a universal disease and the challenges to immigrants in
high prevalence countries.
PMID- 29341369
TI - Structural Factors Affecting Binding of Platinum Anticancer Agents with
Phospholipids: Influence of Charge and Phosphate Clamp Formation.
AB - We report a detailed NMR and DFT study of the interaction of polynuclear platinum
anticancer agents (PPCs) with negatively charged phospholipids as a mechanism for
their cellular uptake. The reactions of fully 15 N-labelled [{trans-PtCl(NH3 )2
}2 (MU-trans-Pt(NH3 )2 {NH2 (CH2 )6 NH2 }2 )]4+ (15 N-1, 1,0,1/t,t,t) and the
dinuclear [{trans-PtCl(NH3 )2 }2 {MU-H2 N(CH2 )6 NH2 }]2+ (15 N-2, 1,1/t,t) with
the sodium salt of 1,2-dihexanoyl-sn-glycero-3-phosphate (DHPA) were studied at
298 K, pH ~5.4, by [1 H,15 N] HSQC 2D NMR spectroscopy. Both 15 N-1 and 15 N-2
form an initial mono-adduct in which the DHPA is coordinated via the phosphate O
atom. For the dinuclear 15 N-2, coordination of a second DHPA, in two different
orientations, leads to two conformers of the bifunctional adduct. For 15 N-1,
coordination of the second DHPA allows the central {PtN4 } coordination unit to
bind electrostatically to two additional DHPA molecules via phosphate clamp
interactions, in an extended network. For both 1,0,1/t,t,t (1) and 1,1/t,t (2),
equilibrium conditions are obtained more slowly (>35 h) than in the presence of
phosphate (12 h) and in each case the rate constant for the first step of DHPA
binding (kL ) is about 8 times higher than that for phosphate, whereas the rate
constants for the reverse reactions are quite similar. Reaction of 15 N-1 with
the sodium salt of 1,2-dihexanoyl-sn-glycero-3-[phosphatidyl-l-serine] (DHPS)
showed only minor adduct formation via coordination to the N-donor atom of the
phosphoserine group.
PMID- 29341370
TI - Real-world clinical outcomes and predictors of glycaemic and weight response to
exenatide once weekly in patients with type 2 diabetes: The CIBELES project.
AB - AIMS: To evaluate in a real-world setting the effectiveness of exenatide once
weekly (ExQW) in patients with T2D and to determine predictors of glycaemic and
weight response to this drug at 6 months. METHODS: Observational, retrospective,
multicenter study in adult patients with T2D and BMI >=30 kg/m2 from 4 tertiary
Spanish hospitals who started ExQW therapy at least 6 months before the inclusion
and had not achieved adequate glycaemic control on oral therapies or other GLP-1
receptor agonists. Glycaemic response was defined as an A1C reduction >=1.0% and
weight response as a weight loss >=3% 6 months after ExQW. The best predictive
models of glycaemic and weight response were estimated by binary logistic
regression. RESULTS: One hundred and forty eight patients were included, mean age
58.0 years, A1C 7.7%, weight 105.9 kg and BMI 38.4 kg/m2 . A1C (-1.1%), weight (
3.9 kg), systolic blood pressure (-4.0 mm Hg), diastolic blood pressure (-2.9 mm
Hg), LDL-cholesterol (-14.2 mg/dL) and triglycerides (-31.0 mg/dL) significantly
decreased 6 months after ExQW. 41.5% of patients had an A1C reduction >=1.0% and
53.1% lost >=3% of baseline weight. Glycaemic and weight reductions were
sustained in patients completing 1 and 2 years of follow-up. The best predictive
model of glycaemic response only included higher A1C levels (OR 3.9), whereas
higher BMI (OR 1.1) and prior DPP-4i therapy (OR 3.1) were associated to weight
response in the multivariate analysis. CONCLUSIONS: In a real-world setting, ExQW
significantly decreased A1C, weight, blood pressure and lipids at 6 months. Our
study identified higher baseline A1C as the sole independent predictor of
glycaemic response to ExQW and higher BMI and previous DDP4i treatment as
predictive factors of meaningful weight response.
PMID- 29341371
TI - Electrochemical monitoring of aflatoxin M1 in milk samples using silver
nanoparticles dispersed on alpha-cyclodextrin-GQDs nanocomposite.
AB - Aflatoxins are potential food pollutants produced by fungi. One of important
toxins is aflatoxin M1 (AFM1). A great deal of concern is associated with AFM1
toxicity. In the present study, an innovative electrochemical interface for
quantitation of AFM1 based on ternary signal amplification strategy was
fabricated. In this work, silver nanoparticles was electrodeposited onto green
and biocompatible nanocomposite containing alpha-cyclodextrin as conductive
matrix and graphene quantum dots as amplification element. Therefore, a
multilayer film based on alpha-cyclodextrin, graphene quantum dots, and silver
nanoparticles was exploited to develop a highly sensitive electrochemical sensor
for detection of AFM1. Fully electrochemical methodology was used to prepare a
transducer on a glassy carbon electrode, which provided a high surface area
toward sensitive detection of AFM1. The surface morphology of electrode surface
was characterized by high-resolution field emission scanning electron microscope.
The proposed sensing platform provides a simple tool for AFM1 detection. Under
optimized condition, the calibration curve for AFM1 concentration was linear in
0.015mM to 25mM with low limit of quantification of 2MUM. The practical
analytical utility of the modified electrode was illustrated by determination of
AFM1 in unprocessed milk samples.
PMID- 29341372
TI - Renal transplantation in children under 3 years of age: Experience from a single
center study.
AB - RTx remains challenging in children under 3 years of age. This single-center
study reviewed the medical records of children <3 years transplanted since 1987
(N = 32, Group 1). They were matched for donor type and RTx period with children
aged 3-13 years (N = 32, Group 2) and 13-18 years (N = 32, Group 3). There were
no between-group significant differences regarding distributions of gender,
primary renal disease, proportion of dialysis before RTx, and growth (SDS).
Compared to Groups 2 and 3, Group 1 had more peritoneal dialyses (P < .001), more
EBV mismatches (P = .04), and longer warm ischemia times (P < .001). The risk of
graft loss was not significantly different among age groups (hazard ratio, 2.4 in
Group 2 and 2.0 in Group 3 vs Group 1; P = .2). Death occurred in four patients
(3 in Group 1 and 1 in Group 2) and graft loss occurred in 28 patients, mainly
due to chronic allograft nephropathy. In recipients <3 years of age, the outcomes
of RTx are close to those obtained in older pediatric age groups. Thus, young
patients may be transplanted in experienced multidisciplinary teams without
additional risks provided that particular attention is paid to donor selection
and prevention/early diagnosis of comorbidities and complications.
PMID- 29341373
TI - Antibiotic allergy labels-the impact of taking a clinical history.
AB - BACKGROUND: Many patients admitted to hospital have an antibiotic allergy (AAL)
documented in their medical record. In many of these, the reaction is not a
hypersensitivity reaction or may no longer be relevant. Despite this, the label
adversely affects patient care directly in terms of antibiotic selection, and
indirectly in terms of patient costs and the development of antimicrobial
resistance. AIMS: To estimate the prevalence of AALs in a cohort of hospitalised
patients, to investigate the feasibility of de-labelling through re-challenge
based solely upon clinical grounds. DESIGN: This is a cross-sectional study
conducted over a 6-month period on adult inpatients. An allergy history was taken
from each patient and compared with medical record data regarding allergy.
Antibiotic selection data were collected (if relevant). It was then determined
whether immediate de-labelling was appropriate, if direct provocation test (DPT)
could be relatively safely performed, and if antibiotic selection was
appropriate. RESULTS: Three thousand eight hundred and fifty five patients were
screened, 553 (14.35%) had an AAL, and 352 were interviewed. There were 426 AALs;
276 (64.8%) towards a penicillin. After taking a detailed clinical history of the
type of reaction, approximately 20% could be immediately de-labelled and educated
(non-allergic, non-severe reactions) and another 38% with either a definite or
vague history of mild cutaneous reaction would be suitable for an attempt at
clinical de-labelling DPT. CONCLUSIONS: These simple measures to 'de-label'
patients appropriately, would increase the quality of care of this group known to
have higher costs, infection with more resistant bacteria and worse health
outcomes that 'non-labelled' patients.
PMID- 29341374
TI - Validation of the digital PCR system in tyrosine kinase inhibitor-resistant EGFR
mutant non-small-cell lung cancer.
AB - The aim of this study was to compare the accuracy of the QuantStudio 3D Digital
polymerase chain reaction (dPCR) system and a PCR-based next generation
sequencing (NGS) system for detecting a secondary mutation in the epidermal
growth factor receptor (EGFR) gene T790M in non-small cell lung cancer (NSCLC)
patients previously diagnosed with EGFR-activating mutations. Twenty-five
patients with NSCLC previously treated with EGFR-TKIs were examined. The patients
were treated daily with either erlotinib or gefitinib. New biopsies, followed by
DNA sequencing on an Ion Torrent systems using the Ion Torrent AmpliSeq Cancer
Hotspot Panel and dPCR were performed. A comparison of NGS, sensitive PCR, and
dPCR revealed that the sensitivities of NGS and dPCR were similar in this study.
As well, T790M was detected in as low as about 5% of mutant allelic frequencies,
which represented 5% of the total reads on site mapped reads in NGS and greater
than 5% of the dPCR reads, which represented mutant and wild type copies. The
strategy in which NGS sequencing is followed by revealed acquired mutation with
dPCR may be a reasonable one. We demonstrated the utility of combining NGS and
dPCR as a tool for monitoring T790M. NGS and dPCR with formalin-fixed paraffin
embedded (FFPE) specimens might become a standard genomic test for exploring
acquired resistance to targeted molecular medicines.
PMID- 29341375
TI - Transparency-enhancing technology allows three-dimensional assessment of
gastrointestinal mucosa: A porcine model.
AB - Although high-resolution three-dimensional imaging of endoscopically resected
gastrointestinal specimens can help elucidating morphological features of
gastrointestinal mucosa or tumor, there are no established methods to achieve
this without breaking specimens apart. We evaluated the utility of transparency
enhancing technology for three-dimensional assessment of gastrointestinal mucosa
in porcine models. Esophagus, stomach, and colon mucosa samples obtained from a
sacrificed swine were formalin-fixed and paraffin-embedded, and subsequently
deparaffinized for analysis. The samples were fluorescently stained, optically
cleared using transparency-enhancing technology: ilLUmination of Cleared organs
to IDentify target molecules method (LUCID), and visualized using laser scanning
microscopy. After observation, all specimens were paraffin-embedded again and
evaluated by conventional histopathological assessment to measure the impact of
transparency-enhancing procedures. As a result, microscopic observation revealed
horizontal section views of mucosa at deeper levels and enabled the three
dimensional image reconstruction of glandular and vascular structures. Besides,
paraffin-embedded specimens after transparency-enhancing procedures were all
assessed appropriately by conventional histopathological staining. These results
suggest that transparency-enhancing technology may be feasible for clinical
application and enable the three-dimensional structural analysis of endoscopic
resected specimen non-destructively. Although there remain many limitations or
problems to be solved, this promising technology might represent a novel
histopathological method for evaluating gastrointestinal cancers.
PMID- 29341376
TI - Effects of Playback Theatre on cognitive function and quality of life in older
adults in Singapore: A preliminary study.
AB - OBJECTIVE: This study investigated the effects of Playback Theatre on older
adults' cognitive function and well-being, specifically in the Singapore context.
METHODS: Eighteen healthy older adults, older than 50 years of age, participated
in the study. Due to practical limitations, a single-group pre-post study design
was adopted. Participants completed the outcome measures before and after the
training program. There were six weekly sessions in total (about 1.5 hours, once
weekly). RESULTS: Participants experienced a significant improvement in their
emotional well-being after training. However, there were no significant changes
in participants' cognitive function or health-related quality of life.
CONCLUSION: Our results suggest that Playback Theatre as a community program has
potential to improve the mental and emotional well-being of older people.
PMID- 29341377
TI - Halogen Bonding in Solution: Anion Recognition, Templated Self-Assembly, and
Organocatalysis.
AB - The halogen bond is a supramolecular interaction between a Lewis-acidic region of
a covalently bound halogen and a Lewis base. It has been studied widely in silico
and experimentally in the solid state; however, solution-phase applications have
attracted enormous interest in the last few years. This Minireview highlights
selected recent developments in halogen bond interactions in solution, with a
focus on the use of receptors based on halogen bonds in anion recognition and
sensing, anion-templated self-assembly, as well as in organocatalysis.
PMID- 29341378
TI - Halloysite Nanotubes: Green Nanomaterial for Functional Organic-Inorganic
Nanohybrids.
AB - The unique one-dimensional nanoporous structure and the reactive external and
internal surfaces make halloysite nanotube (HNT) an interesting nanomaterial for
various applications. HNT is a green nanomaterial because it is easily available
from abundant deposits in nature and is biocompatible with low cytotoxicity.
After a brief introduction on the structure of HNT, recent advances in surface
modification of HNT and its functional organic-inorganic nanohybrids including
hybrid nanocontainers, flame retardant nanocomposites, dye removal adsorbents,
liquid marbles, and superamphiphobic coatings are introduced.
PMID- 29341379
TI - Erector spinae plane block for inguinal hernia repair in preterm infants.
AB - Neuro-axial anesthesia has been the preferred technique for inguinal hernia
repair when attempting to avoid general anesthesia in neonates and preterm
infants. We present a case where an erector spinae plane block was used
successfully for this surgery. Hemodynamic stability, minimal anesthetic
requirements, and excellent pain control were documented. This block promises to
be a valuable and safe alternative for inguinal hernia repair, accompanying the
path of neuroprotective anesthesia.
PMID- 29341380
TI - Tuning the Adsorption Energy of Methanol Molecules Along Ni-N-Doped Carbon Phase
Boundaries by the Mott-Schottky Effect for Gas-Phase Methanol Dehydrogenation.
AB - Engineering the adsorption of molecules on active sites is an integral and
challenging part for the design of highly efficient transition-metal-based
catalysts for methanol dehydrogenation. A Mott-Schottky catalyst composed of Ni
nanoparticles and tailorable nitrogen-doped carbon-foam (Ni/NCF) and thus tunable
adsorption energy is presented for highly efficient and selective dehydrogenation
of gas-phase methanol to hydrogen and CO even under relatively high weight hourly
space velocities (WHSV). Both theoretical and experimental results reveal the key
role of the rectifying contact at the Ni/NCF boundaries in tailoring the electron
density of Ni species and enhancing the absorption energies of methanol
molecules, which leads to a remarkably high turnover frequency (TOF) value (356
mol methanol mol-1 Ni h-1 at 350 degrees C), outpacing previously reported
bench-marked transition-metal catalysts 10-fold.
PMID- 29341381
TI - Effect of ethanol on the antimicrobial properties of chlorhexidine over oral
biofilm.
AB - The aim of this study was to evaluate the effect of 95% ethanol irrigation, with
5 or 10 min of action, on the antibacterial properties of 2% chlorhexidine (CHX),
on oral biofilm, evaluated with confocal laser scanning microscopy (CLSM). Oral
biofilm development was induced in 80 sterilized bovine dentin blocks,
distributed in two groups (5 or 10 min) and 4 subgroups, according to time and
the solution used: Saline (SALINE5, SALINE10); Saline followed by CHX
(SALINE/CHX5, SALINE/CHX10); Ethanol (ETHANOL5, ETHANOL10), Ethanol followed by
CHX (ETHANOL/CHX5, ETHANOL/CHX10). The surface of the block was dyed with
Live/Dead(r) BacLight. Images from different areas were analyzed by BioImage L
program. The total biovolum (um3), biovolum of live cells (green), percentage of
live cells of the thickness of the biofilm visualized in CLSM and on surface
biofilm were evaluated. Total biovolum and biovolum of living cells showed
similar results among the different groups (p > .05). The percentage of living
cells in total thickness of the biofilm also was similar among the groups (p >
.05), except ETHANOL5, SALINE/CHX10, ETHANOL10, and ETHANOL/CHX10 that showed
lower percentage than SALINE5 (p < .05). The ETHANOL10 and ETHANOL/CHX10 also
showed lower percentage of living cells than ETHANOL/CHX5 and SALINE10 (p < .05).
In relation to biofilm surface, SALINE/CHX5, SALINE/CHX10, ETHANOL5, ETHANOL10,
ETHANOL/CHX5, and ETHANOL/CHX10 showed a lower percentage of living cells
percentage than SALINE5 and SALINE10 groups (p < .05). Therefore, ethanol has no
effect on antimicrobial properties of 2% chlorhexidine, prior when used as
endodontic irrigating solution.
PMID- 29341382
TI - Synthesis, Crystal Analysis, and Optoelectronic Properties of Diazole
Functionalized Acenes and Azaacenes.
AB - Doping heteroatoms into the skeletons of parent acenes can provide more
opportunities to construct novel thermally and photostable organic pi-conjugated
semiconductors. Herein, a family of diazole-decorated acenes (APyS and APySe) and
azaacenes (PyP, PyTh, PyPy, PyPh, and PyAP) have been successfully synthesized
through the classical reactions. Single-crystal X-ray analyses showed that these
as-formed diazole-modified derivatives adopted a twisted topology configuration,
whereas the azaacenes display reclining-chair architectures, besides a twisted
structure. All these compounds displayed yellow or red light in solution.
Moreover, their electrochemical behaviors were also examined. We also found that
the azaacenes exhibited a positive spectroscopic response to acid.
PMID- 29341383
TI - CO2 -Triggered Switchable Hydrophilicity of a Heterogeneous Conjugated Polymer
Photocatalyst for Enhanced Catalytic Activity in Water.
AB - Water compatibility for heterogeneous photocatalysts has been pursued for energy
and environmental applications. However, there exists a trade-off between
hydrophilicity and recyclability of the photocatalyst. Herein, we report a
conjugated polymer photocatalyst with tertiary amine terminals that reversibly
binds CO2 in water, thereby generating switchable hydrophilicity. The CO2
assisted hydrophilicity boosted the photocatalytic efficiency in aqueous medium
with minimum dosage. When CO2 was desorbed, the photocatalyst could be simply
regenerated from reaction media, facilitating the repeated use of photocatalyst.
Hydrophilicity/hydrophobicity control of the polymer photocatalyst was
successfully showcased through a variety of organic photoredox reactions under
visible-light irradiation in water.
PMID- 29341384
TI - Influence of spore and carrier material surface hydrophobicity on decontamination
efficacy with condensing hydrogen peroxide vapour.
AB - AIMS: To investigate the influence of surface hydrophobicity of carrier material
(CM) and bacterial spores of Bacillus subtilis SA 22 and Bacillus atrophaeus (DSM
675) on spore inactivation with condensing hydrogen peroxide (H2 O2 ) gas.
METHODS AND RESULTS: Surface hydrophobicity of bacterial spores and CM was
determined by means of contact angle measurement. Spores of B. subtilis showed
water contact angles of 90 degrees , spores of B. atrophaeus showed water contact
angles of 42 degrees . Above that, a resistance test against liquid H2 O2 at room
temperature was conducted with resulting DH2O2 values of 101 s (B. subtilis) and
906 s (B. atrophaeus). The spores were deposited on CMs of different wettability
(water contact angles of 115-30 degrees ). The spores were applied either
individually or as an 1 : 1 mixture of both spore species. Exposure of biological
indicators (BI) with 5200 ppm of gaseous H2 O2 at 70 degrees C treatment
temperature for defined times up to 10 s led to inactivation kinetics. Surfaces
with high hydrophobicity showed faster spore inactivation than surfaces with
lower hydrophobicity for single-spore species. Regarding the mixed BI, better
survival of hydrophobic spores was expected. However, this effect can only be
seen as a slight trend and is not significant after 10 s. CONCLUSIONS: Surface
hydrophobicity of CMs does influence the decontamination with gaseous, condensing
H2 O2 . However, surface hydrophobicity of spores in a mixed population does only
have a small influence on inactivation results. SIGNIFICANCE AND IMPACT OF THE
STUDY: The intensity of spore inactivation depends more on other factors than on
the wettability of the bacterial spores. However, hydrophobic surfaces lead to
faster inactivation effects and should thus be preferred for aseptic packaging
technology.
PMID- 29341385
TI - Biological and behavioral correlates of body weight status among rural Northeast
Brazilian schoolchildren.
AB - OBJECTIVES: The increase in the prevalence of overweight/obesity in youth is a
public health problem worldwide; however, few studies have investigated its
prevalence and correlates in children from the Brazilian Northeast region rural
zone. The purpose of this study was (1) to estimate the prevalence of children's
weight status according to sex, age, and birth weight categories; and (2) to
investigate the links between biological and behavioral factors and weight
categories. METHODS: The sample comprises 501 children (248 girls), aged 7-10
years, classified as low weight, normal weight, overweight, and obese using body
mass index cut-points. Predicted variables included birth weight, percentage of
body fat (%BF), fat free mass (FFM), physical fitness, and gross motor
coordination. RESULTS: Data showed differences among weight groups for the
predictor variables. Results of the logistic regression revealed that sex, age,
%BF, FFM, physical fitness, and motor coordination seem to be relevant predictors
of children's weight status, while no significant effect was observed for birth
weight. CONCLUSION: Children with lower physical fitness levels as well as those
with lower motor coordination quotient are more likely to be overweight and/or
obese. No significant relationship was observed between birth weight and weight
status in childhood. Strategies to reduce childhood obesity should consider
biological, behavioral, and also environmental predictors.
PMID- 29341386
TI - At the core of reasoning: Dissociating deductive and non-deductive load.
AB - In recent years, neuroimaging methods have been used to investigate how the human
mind carries out deductive reasoning. According to some, the neural substrate of
language is integral to deductive reasoning. According to others, deductive
reasoning is supported by a language-independent distributed network including
left frontopolar and frontomedial cortices. However, it has been suggested that
activity in these frontal regions might instead reflect non-deductive factors
such as working memory load and general cognitive difficulty. To address this
issue, 20 healthy volunteers participated in an fMRI experiment in which they
evaluated matched simple and complex deductive and non-deductive arguments in a 2
* 2 design. The contrast of complex versus simple deductive trials resulted in a
pattern of activation closely matching previous work, including frontopolar and
frontomedial "core" areas of deduction as well as other "cognitive support" areas
in frontoparietal cortices. Conversely, the contrast of complex and simple non
deductive trials resulted in a pattern of activation that does not include any of
the aforementioned "core" areas. Direct comparison of the load effect across
deductive and non-deductive trials further supports the view that activity in the
regions previously interpreted as "core" to deductive reasoning cannot merely
reflect non-deductive load, but instead might reflect processes specific to the
deductive calculus. Finally, consistent with previous reports, the classical
language areas in left inferior frontal gyrus and posterior temporal cortex do
not appear to participate in deductive inference beyond their role in encoding
stimuli presented in linguistic format.
PMID- 29341387
TI - Health service utilisation amongst urban Aboriginal and Torres Strait Islander
children aged younger than 5 years registered with a primary health-care service
in South-East Queensland.
AB - AIM: The majority of Australia's Aboriginal and/or Torres Strait Islander
children live in urban areas; however, little is known about their health service
use. We aimed to describe health service utilisation amongst a cohort of urban
Aboriginal and/or Torres Strait Islander children aged <5 years. METHODS: We
analysed health service utilisation data collected in an ongoing prospective
cohort study of children aged <5 years registered with an Aboriginal-owned and
operated primary health-care service. Enrolled children were followed monthly for
12 months, with data on health service utilisation collected at baseline and at
each monthly follow-up. Health service utilisation rates, overall and by service
provider and reason for presentation, were calculated and reported as incidence
rates per 100 child-months with the corresponding 95% confidence intervals (CIs).
RESULTS: Between February 2013 and November 2015, 180 children were enrolled, and
1541 child-months of observation were available for analysis. The overall
incidence of health service utilisation was 52.5 per 100 child-months (95% CI
48.7-56.5); 81% of encounters were with general practitioners. Presentation rates
were the highest for acute respiratory illnesses (30.7/100 child-months, 95% CI
27.8-33.9). CONCLUSIONS: In this community, acute respiratory illnesses are
predominant causes of health service utilisation in young children. The health
care utilisation profile of these children presents important opportunities for
health promotion and intervention.
PMID- 29341388
TI - Venous anastomosis by piggyback technique to avoid twisting of the pediatric en
bloc kidney grafts.
AB - This is the first report of using piggyback technique for the venous anastomosis
in two pediatric recipients of small en bloc kidneys, which was found to be
effective to avoid twisting of the grafts and vessels. The donors were aged 2 and
3 years with a body weight of 17 and 20 kg. The recipient age was 14 and 16 years
with a body weight of 42 and 54 kg. The implantation was done extraperitoneally
in the right iliac fossa. The donor's inferior vena cava was anastomosed to the
recipient's distal caval vein side-to-side using 6-0 polydioxanone running suture
as the piggyback technique, initially dealing with the short vena cava graft in
the first case. At the end of the operation, the kidneys were positioned allowing
the lateral aspect of each renal unit to face anteriorly as "closing the book."
The cold ischemia time was 895 and 820 minutes, respectively. No vascular
complication was observed postoperatively. The patients were discharged on POD 16
and POD 21 with an eGFR of 94 and 102 mL/min/1.73 m2, respectively. The graft
function is stable during the 5- and 7-month follow-up.
PMID- 29341389
TI - Detection of Escherichia coli in ready-to-eat fresh vegetables using broad-host
range recombinant phages.
AB - AIM: To construct a simple method to detect Escherichia coli in ready-to-eat
fresh vegetables using broad-host-range recombinant phages. METHODS AND RESULTS:
Firstly, a gene encoding cytochrome c peroxidase (CCP) chromogenic enzyme was
inserted into genomes of wild-type phages IP008 and IP052 to produce recombinant
phages IP008BK and IP052BK. They were then used in the production of the
chromogenic enzyme (CCP) through infection into E. coli. The method was then
examined in the colorimetric detection of E. coli K12 in broth, and its
appearance was confirmed by a significant change in absorbance after a few
minutes of the enzyme assay. Secondly, the protocol using the recombinant phages
for the detection of E. coli in vegetables, that is, lettuce and mustard greens,
was investigated. A low E. coli concentration at 4 CFU per g vegetable was
detected within 16.5 h that is of a shorter duration than agar plate methods and
in some commonly known phage-based methods. CONCLUSION: The existence of E. coli
as a faecal contamination indicator in two types of ready-to-eat fresh
vegetables, that is, lettuce and mustard greens, can be identified by the broad
host-range recombinant phages. SIGNIFICANCE AND IMPACT OF STUDY: The method is
simple and convenient since it enables the detection of E. coli without expensive
apparatus. It is applicable to other types of food samples.
PMID- 29341391
TI - Control of Protein Activity and Gene Expression by Cyclofen-OH Uncaging.
AB - The use of light to control the expression of genes and the activity of proteins
is a rapidly expanding field. Whereas many of these approaches use fusion between
a light-activable protein and the protein of interest to control the activity of
the latter, it is also possible to control the activity of a protein by uncaging
a specific ligand. In that context, controlling the activation of a protein fused
to the modified estrogen receptor (ERT) by uncaging its ligand cyclofen-OH has
emerged as a generic and versatile method to control the activation of proteins
quantitatively, quickly, and locally in a live organism. We present that approach
and its uses in a variety of physiological contexts.
PMID- 29341392
TI - Cannabis use is associated with reduced prevalence of progressive stages of
alcoholic liver disease.
AB - BACKGROUND: Abusive alcohol use has well-established health risks including
causing liver disease (ALD) characterized by alcoholic steatosis (AS),
steatohepatitis (AH), fibrosis, cirrhosis (AC) and hepatocellular carcinoma
(HCC). Strikingly, a significant number of individuals who abuse alcohol also use
Cannabis, which has seen increased legalization globally. While cannabis has
demonstrated anti-inflammatory properties, its combined use with alcohol and the
development of liver disease remain unclear. AIM: The aim of this study was to
determine the effects of cannabis use on the incidence of liver disease in
individuals who abuse alcohol. METHODS: We analysed the 2014 Healthcare Cost and
Utilization Project-Nationwide Inpatient Sample (NIS) discharge records of
patients 18 years and older, who had a past or current history of abusive alcohol
use (n = 319 514). Using the International Classification of Disease, Ninth
Edition codes, we studied the four distinct phases of progressive ALD with
respect to three cannabis exposure groups: non-cannabis users (90.39%), non
dependent cannabis users (8.26%) and dependent cannabis users (1.36%). We
accounted for the complex survey sampling methodology and estimated the adjusted
odds ratio (AOR) for developing AS, AH, AC and HCC with respect to cannabis use
(SAS 9.4). RESULTS: Our study revealed that among alcohol users, individuals who
additionally use cannabis (dependent and non-dependent cannabis use) showed
significantly lower odds of developing AS, AH, AC and HCC (AOR: 0.55 [0.48-0.64],
0.57 [0.53-0.61], 0.45 [0.43-0.48] and 0.62 [0.51-0.76]). Furthermore, dependent
users had significantly lower odds than non-dependent users for developing liver
disease. CONCLUSIONS: Our findings suggest that cannabis use is associated with a
reduced incidence of liver disease in alcoholics.
PMID- 29341390
TI - Building a new research framework for social evolution: intralocus caste
antagonism.
AB - The breeding and non-breeding 'castes' of eusocial insects provide a striking
example of role-specific selection, where each caste maximises fitness through
different morphological, behavioural and physiological trait values. Typically,
queens are long-lived egg-layers, while workers are short-lived, largely sterile
foragers. Remarkably, the two castes are nevertheless produced by the same
genome. The existence of inter-caste genetic correlations is a neglected
consequence of this shared genome, potentially hindering the evolution of caste
dimorphism: alleles that increase the productivity of queens may decrease the
productivity of workers and vice versa, such that each caste is prevented from
reaching optimal trait values. A likely consequence of this 'intralocus caste
antagonism' should be the maintenance of genetic variation for fitness and
maladaptation within castes (termed 'caste load'), analogous to the result of
intralocus sexual antagonism. The aim of this review is to create a research
framework for understanding caste antagonism, drawing in part upon conceptual
similarities with sexual antagonism. By reviewing both the social insect and
sexual antagonism literature, we highlight the current empirical evidence for
caste antagonism, discuss social systems of interest, how antagonism might be
resolved, and challenges for future research. We also introduce the idea that
sexual and caste antagonism could interact, creating a three-way antagonism over
gene expression. This includes unpacking the implications of haplodiploidy for
the outcome of this complex interaction.
PMID- 29341393
TI - Prognostic and therapeutic factors influencing the clinical outcome of
hepatoblastoma after liver transplantation: A single-institute experience.
AB - LT has contributed to an elevation in cure rates for patients with unresectable
HB; however, patients with recurrent HB after LT have poor prognosis. To analyze
the prognostic and therapeutic factors that influence the clinical outcome of
patients with HB receiving LT, we retrospectively analyzed 24 patients with HB
who underwent LT between 1997 and 2015. The 5-year OS rate of all patients was
69.6+/-9.7%. The 5-year OS rate of 11 patients receiving salvage LT for recurrent
tumor after a primary resection was comparable to that of 13 patients receiving
primary LT. Among 12 evaluable patients receiving primary LT, six of 10 patients
with a decline of serum AFP >95% at LT are currently alive and in remission,
whereas two patients with a decline of AFP <=95% experienced post-LT relapse.
Among 9 evaluable patients receiving salvage LT, all three patients with any
decline of AFP at LT are currently alive in remission, and three of six patients
with no response to pre-LT salvage chemotherapy are also alive and in remission.
Response to chemotherapy may be a reliable marker for prediction of post-LT
relapse, even for patients receiving salvage LT.
PMID- 29341394
TI - Hydrolysis by catalytic IgGs of microRNA specific for patients with
schizophrenia.
AB - Significant importance of autoimmune changes in the pathogenesis of schizophrenia
(SCZ) is not established. Here, we present the first evidence that autoantibodies
of 100% SCZ patients possess RNase activity: sCMP > poly(C) > poly(A) > yeast
RNA. In addition, we have got an unexpected result: there was revealed site
specific hydrolysis of four known SCZ specific microRNAs (miR-137, miR-9-5p, miR
219-2-3p, and miR-219a-5p) playing an important role in the regulation of several
genes functioning. Three major of cleavage sites are located in the microRNA
loops or duplex parts directly articulated with the loops. RNase abzymes can
contribute to decreasing of microRNAs effects on the functioning of numerous
genes and the products of their transcription. Therefore, abzymes with RNase
activity may be to some extent important for the development of schizophrenia.
(c) 2018 IUBMB Life, 70(2):153-164, 2018.
PMID- 29341395
TI - Health of Southern Tasmanian 4- to 6-year-old children in out-of-home care
compared to peers.
AB - AIM: To compare the health of 4- to 6-year-old children in out-of-home care
(OOHC) in Southern Tasmania with their peers. METHODS: Demographic and health
data collection and prospective health assessment of all 4- to 6-year olds in
OOHC in Southern Tasmania on 30 August 2011 was undertaken. Data were compared to
Tasmanian and/or Australian peers. RESULTS: A total of 109 of 129 children aged 4
to 6 years were included in the study. Time in OOHC was on average 38 (range 0
76) months. Premature birth (18%), low birthweight (20%) and congenital
malformations (10%) were more common compared to peers. Antenatal exposure to
illicit or abused substances (71%), alcohol (51%) and cigarettes (79%) were very
high. Vertically acquired hepatitis C was diagnosed in 2% with 33% exposed.
Immunisation completion was 78% compared to 92.9% of Tasmanian peers. Obesity
(11% vs. 6% Tasmanian children), hearing impairment (7% vs. 1% Tasmanian
children) and dental caries (61% vs. 45% Tasmanian children) were all higher than
peers. Hospitalisation due to injury was more than twice that of Tasmanian peers
(32.1 vs. 12.6 per 1000 per year). Developmental delay was 50% on screening.
Emotional or behavioural difficulties were seen in 54%. CONCLUSIONS: Children in
OOHC have high health needs. Comprehensive health assessments offer an
opportunity to better identify and manage these needs. High hepatitis C exposure
in utero was unexpected. This study highlights the need for comprehensive health
screening assessments for all children in OOHC. OOHC clinic data can be helpful
in planning broad interventions for children in OOHC.
PMID- 29341396
TI - Pediatrics and donor-derived disease transmission: The US OPTN experience.
AB - PDDTE are tracked by the OPTN Ad Hoc DTAC. Specific evaluation of potential
transmissions from pediatric deceased donors or the impact of donor-derived
disease transmissions to pediatric organ recipients has not been previously
undertaken. PDDTE reported to the DTAC between 2008 and 2013 were reviewed,
characterized as proven, probable, possible, IWDT, unlikely, or excluded for both
the whole event and each individual recipient. Pediatric donors and recipients
were defined as being 0-17 years of age. Analysis was undertaken to characterize
potential disease transmission from pediatric donors to adult or pediatric
recipients and also to evaluate potential transmission from all donors to
pediatric recipients. P/P cases were further analyzed. A total of 5238 pediatric
deceased US donors accounted for 17 456 organ transplants during the study
period; 103 PDDTE reports arose from these donors (2.0%). PDDTE were
characterized as P/P (15%), possible (13%), IWDT (9%), unlikely, and excluded
(63%). Disease was transmitted to 22 of 54 potentially exposed (adult and
pediatric) recipients with six attributable deaths. An infectious pathogen
accounted for 13/15 of the P/P PDDTE associated with pediatric donors, affecting
19 of 50 potentially exposed recipients and resulting in five deaths. Four
separate viral pathogens from six donors accounted for P/P transmissions to 11
recipients with the unanticipated transmission of CMV most common. No pediatric
donor transmitted HIV, HBV, or HCV. Bacteria, fungi, and parasites accounted for
three (all staphylococci), three (Zygomycetes and Histoplasma), and two (both
Toxoplasma) P/P transmissions from seven donors, respectively. From the recipient
side, 11/11,188 pediatric recipient deceased and living donor transplants during
the study period were associated with a P/P PDDTE (<0.1%) with infectious
pathogens accounting for 9/11 P/P events. Infections were split among pathogen
categories (bacteria 2, viruses 3, parasites 3, and fungi 1). Reporting rates of
PDDTE involving pediatric donors were very low and similar to rates from all
donors, with resulting P/P transmissions occurring in only 0.1% of exposed
recipients, but transmissions were associated with six deaths. Rates of P/P
transmission to pediatric recipients from any donor (<0.1%) were also very low
and similar to that of all recipients. Additional studies are needed to compare
the pattern and outcome of donor-derived disease transmission from and to
pediatric and adult donor and recipients.
PMID- 29341397
TI - Bi-allelic mutations of CCDC88C are a rare cause of severe congenital
hydrocephalus.
AB - Congenital or infantile hydrocephalus is caused by genetic and non-genetic
factors and is highly heterogeneous in etiology. In recent studies, a limited
number of genetic causes of hydrocephalus have been identified. To date,
recessive mutations in the CCDC88C gene have been identified as a cause of non
syndromic congenital hydrocephalus in three reported families. Here, we report
the fourth known family with two affected individuals with congenital
hydrocephalus due to a homozygous mutation in the CCDC88C gene identified by
whole exome sequencing. Our two newly described children, as well as the
previously published ones, all shared several features including severe infantile
onset hydrocephalus, mild to severe intellectual delay, varying degrees of motor
delay, and infantile onset seizures. All identified homozygous mutations in
CCDC88C abolish the PDZ binding site necessary for proper CCDC88C protein
function in the Wnt signaling pathway. Our report further establishes CCDC88C as
one of the few known recessive causes of severe prenatal-onset hydrocephalus.
Recognition of this syndrome has important diagnostic and genetic implications
for families identified in the future.
PMID- 29341398
TI - What are the outcomes of declining a public health service increased risk liver
donor for patients on the liver transplant waiting list?
AB - The tragedy of the national opioid epidemic has resulted in a significant
increase in the number of opioid-related deaths and accordingly an increase in
the number of potential donors designated Public Health Service (PHS) increased
risk. Previous studies have demonstrated reluctance to use these PHS organs, and
as a result, higher discard rates for these organs have been observed. All
patients listed for liver transplantation in the United States from January 2005
to December 2016 were investigated. Patients on the waiting list were divided
into 2 groups: those in which a PHS liver was used for transplantation (accepted
PHS group) and those in which a PHS liver was declined and transplanted into a
recipient lower on the match run (declined PHS group). Intention-to-treat patient
survival from the time of PHS offer was significantly higher in the accepted PHS
compared with the declined PHS group (P < 0.001). On Cox multivariate regression,
declining a PHS donor liver was associated with a hazard ratio of 2.36 (95%
confidence interval, 2.23-2.49; P < 0.001). For patients in which a PHS organ
offer was declined, 11.6% died or were delisted for being too sick within the
subsequent year. Donor liver allografts implanted in the accepted PHS group were
of a lower donor risk index (1.28 versus 1.44) compared with the non-PHS organs
that patients in the declined PHS group ultimately received if they underwent
transplantation. In conclusion, there is a significantly higher survival for
patients in which a PHS liver is accepted and used compared with those patients
in which a PHS organ is declined. These data will help inform decisions about
whether or not to accept a PHS donor liver for both patients and transplant
professionals. Liver Transplantation 24 497-504 2018 AASLD.
PMID- 29341399
TI - Activation of the Hog1 MAPK by the Ssk2/Ssk22 MAP3Ks, in the absence of the
osmosensors, is not sufficient to trigger osmostress adaptation in Saccharomyces
cerevisiae.
AB - Yeast cells respond to hyperosmotic stress by activating the high-osmolarity
glycerol (HOG) pathway, which consists of two branches, Hkr1/Msb2-Sho1 and Sln1,
which trigger phosphorylation and nuclear internalization of the Hog1 mitogen
activated protein kinase. In the nucleus, Hog1 regulates gene transcription and
cell cycle progression, which allows the cell to respond and adapt to
hyperosmotic conditions. This study demonstrates that the uncoupling of the known
sensors of both branches of the pathway at the level of Ssk1 and Ste11 impairs
cell growth in hyperosmotic medium. However, under these conditions, Hog1 was
still phosphorylated and internalized into the nucleus, suggesting the existence
of an alternative Hog1 activation mechanism. In the ssk1ste11 mutant,
phosphorylated Hog1 failed to associate with chromatin and to activate
transcription of canonical hyperosmolarity-responsive genes. Accordingly, Hog1
also failed to induce glycerol production at the levels of a wild-type strain.
Inactivation of the Ptp2 phosphatase moderately rescued growth impairment of the
ssk1ste11 mutant under hyperosmotic conditions, indicating that downregulation of
the HOG pathway only partially explains the phenotypes displayed by the ssk1ste11
mutant. Cell cycle defects were also observed in response to stress when Hog1 was
phosphorylated in the ssk1ste11 mutant. Taken together, these observations
indicate that Hog1 phosphorylation by noncanonical upstream mechanisms is not
sufficient to trigger a protective response to hyperosmotic stress.
PMID- 29341400
TI - Are trans diagnostic models of eating disorders fit for purpose? A consideration
of the evidence for food addiction.
AB - Explanatory models for eating disorders have changed over time to account for
changing clinical presentations. The transdiagnostic model evolved from the
maintenance model, which provided the framework for cognitive behavioural therapy
for bulimia nervosa. However, for many individuals (especially those at the
extreme ends of the weight spectrum), this account does not fully fit. New
evidence generated from research framed within the food addiction hypothesis is
synthesized here into a model that can explain recurrent binge eating behaviour.
New interventions that target core maintenance elements identified within the
model may be useful additions to a complex model of treatment for eating
disorders.
PMID- 29341401
TI - The prediction probabilities for emergence from sevoflurane anesthesia in
children: A comparison of the perfusion index and the bispectral index.
AB - BACKGROUND: Predicting recovery of consciousness is one of the most essential
functions of anesthesia depth monitors in anesthesia practice. Perfusion index
and bispectral index are 2 indicators of the anesthesia depth monitoring with
different working principles. The progression of the anesthesia emergence stages
reflected by those monitors has not been well understood, especially in pediatric
patients. The goals of this study were to compare the prediction probabilities of
perfusion index and bispectral index in predicting awakening and in
differentiating the different levels of arousal during emergence after
sevoflurane anesthesia in children undergoing open inguinal hernia repairs.
METHODS: Forty-five patients, aged 1 to 5 years, ASA Status I or II and scheduled
for elective open inguinal hernia repairs under general anesthesia were enrolled.
The perfusion index and bispectral index were monitored simultaneously during
anesthesia recovery. The University of Michigan Sedation Scale was applied to
evaluate the clinical arousal levels during emergence. The prediction probability
was used to assess the performance of perfusion index and bispectral index in
predicting awakening and distinguishing different levels of arousal corresponding
to the University of Michigan Sedation Scale during recovery. RESULTS: The
prediction probability of perfusion index (PkPI-Awakening = .81, 95% CI 0.73
0.89) in differentiating full consciousness from unconsciousness during recovery
was comparable to that of bispectral index (PkBIS- Awakening = .86, 95% CI 0.79
0.92) (P = .47). The prediction probability for perfusion index (PkPI-UMSS =
.61, 95% CI 0.55-0.73) and bispectral index (PkBIS-UMSS = .64, 95% CI 0.53-0.69)
had similar performance in distinguishing different University of Michigan
Sedation Scale levels. CONCLUSION: Both the perfusion index and bispectral index
performed comparably well in predicting awakening and different arousal levels
when emerging from sevoflurane anesthesia in children.
PMID- 29341403
TI - Robotic low anterior resection of rectal cancer with partial resection of urinary
bladder and reconstruction - a video vignette.
PMID- 29341402
TI - Isotope Substitution of Promiscuous Alcohol Dehydrogenase Reveals the Origin of
Substrate Preference in the Transition State.
AB - The origin of substrate preference in promiscuous enzymes was investigated by
enzyme isotope labelling of the alcohol dehydrogenase from Geobacillus
stearothermophilus (BsADH). At physiological temperature, protein dynamic
coupling to the reaction coordinate was insignificant. However, the extent of
dynamic coupling was highly substrate-dependent at lower temperatures. For benzyl
alcohol, an enzyme isotope effect larger than unity was observed, whereas the
enzyme isotope effect was close to unity for isopropanol. Frequency motion
analysis on the transition states revealed that residues surrounding the active
site undergo substantial displacement during catalysis for sterically bulky
alcohols. BsADH prefers smaller substrates, which cause less protein friction
along the reaction coordinate and reduced frequencies of dynamic recrossing. This
hypothesis allows a prediction of the trend of enzyme isotope effects for a wide
variety of substrates.
PMID- 29341404
TI - Intra- and inter-subject variability for increases in serum ketone bodies in
patients with type 2 diabetes treated with the sodium glucose co-transporter 2
inhibitor canagliflozin.
AB - Sodium glucose co-transporter 2 (SGLT2) inhibitors have been associated with
increased serum ketone body levels in patients with type 2 diabetes mellitus
(T2DM). In the present analysis we evaluated serum ketone body levels and
variability in 1278 Japanese patients with T2DM treated with canagliflozin 100 or
200 mg. Similar mean increases in ketone body concentrations of ~2-fold were seen
with both canagliflozin doses. The median (interquartile range) percent change
from baseline was 62% (0;180) for acetoacetate and 78% (2;236) for beta
hydroxybutyrate. Approximately two-thirds of the variability in each ketone
measure was attributed to intra-subject variability. Intra-subject variability
was higher for serum ketones than other metabolites. Patients in the lowest
response tertile exhibited no increase in ketones. Those in the highest response
tertile tended to be male and have higher fasting plasma glucose levels, lower
insulin levels, and longer T2DM duration at baseline. Moreover, changes in serum
ketones were not fully explained by changes in plasma fatty acids, suggesting
downstream effects of SGLT2 inhibition on hepatic metabolism that favour
ketogenesis. In summary, increases in serum ketone bodies with canagliflozin were
greater and more variable than changes in other metabolic measures in Japanese
patients with T2DM.
PMID- 29341405
TI - Haemophilia of the third age.
PMID- 29341406
TI - Biosimilars and haemophilia.
PMID- 29341407
TI - Corrigendum.
PMID- 29341408
TI - IR Spectrum and Structure of Protonated Monosilanol: Dative Bonding between Water
and the Silylium Ion.
AB - We report the spectroscopic characterization of protonated monosilanol (SiH3 OH2+
) isolated in the gas phase, thus providing the first experimental determination
of the structure and bonding of a member of the elusive silanol family. The SiH3
OH2+ ion is generated in a silane/water plasma expansion, and its structure is
derived from the IR photodissociation (IRPD) spectrum of its Ar cluster measured
in a tandem mass spectrometer. The chemical bonding in SiH3 OH2+ is analyzed by
density functional theory (DFT) calculations, providing detailed insight into the
nature of the dative H3 Si+ -OH2 bond. Comparison with protonated methanol
illustrates the differences in bonding between carbon and silicon, which are
mainly related to their different electronegativity and the different energy of
the vacant valence pz orbital of SiH3+ and CH3+ .
PMID- 29341409
TI - Recognition of i-IF/TA as a component of the T cell-mediated rejection spectrum:
Unselected population approach vs random case selection.
PMID- 29341410
TI - Eating down the food chain: generalism is not an evolutionary dead end for
herbivores.
AB - The role of trophic specialisation in taxonomic diversification remains unclear.
Plant specialists diversify faster than omnivores and animalivores, but at
shorter macroevolutionary scales this pattern sometimes reverses. Here, we
estimate the effect of diet diversification on speciation rates in noctilionoid
bats, controlling for tree shape, rate heterogeneity and macroevolutionary
regimes. We hypothesise that niche subdivision among herbivores positively
relates to speciation rates, differing between macroevolutionary regimes. We
found the rate at which new herbivorous lineages originate decreases as rates of
diet evolution increase. Herbivores experience higher speciation rates, but
generalist herbivores and predominantly herbivorous omnivores speciate faster
than specialised herbivores, omnivores and animalivores. Generalised herbivory is
not a dead end. We show that analysing ecological traits and diversification
requires accounting for macroevolutionary regimes and within- and between-clade
variation in evolutionary rates. Our approach overcomes the high false-positive
rates of other methods and illuminates the roles of herbivory and specialisation
in speciation.
PMID- 29341411
TI - The effect of recanalization on long-term neurological outcome after cerebral
venous thrombosis.
AB - : Essentials The role of cerebral venous thrombosis (CVT) recanalization on
neurologic outcome is still debated. We studied a large cohort of 508 CVT
patients with 419 patient years of radiological follow-up. Recanalization rate is
high during the first months after CVT and neurologic outcome is favorable. High
recanalization grade of CVT independently predicts good neurological outcome.
SUMMARY: Background Studies with limited sample size and with discordant results
described the recanalization time-course of cerebral venous thrombosis (CVT). The
neurological outcome after a first episode of CVT is good, but the role of
recanalization on neurological dependence is still debated. Objectives The aim of
the study is to assess the recanalization rate after cerebral venous thrombosis
(CVT) and its prognostic role in long-term neurological outcome. Patients/Methods
In a retrospective observational multicenter cohort study, patients with an acute
first episode of CVT with at least one available imaging test during follow-up
were enrolled. Patency status of the vessels was categorized as complete, partial
or not recanalized. Neurological outcome was defined using the modified Rankin
scale (mRS) as good (mRS = 0-1) or poor (mRS = 2-6). Results Five-hundred and
eight patients (median [IQR] age, 39 [28.5-49] years; 26% male) were included.
Complete or partial recanalization was not differently represented in patients
undergoing scans at different periods of time (from 28-day to 3 month-period up
to a 1-3 year-period). mRS at the time of follow-up imaging was available in 483
patients; 92.8% of them had a mRS of 0-1. CVT recanalization (odds ratio [OR],
2.56; 95% confidence interval [CI], 1.59-4.13) was positively associated, whereas
cancer (OR, 0.29; 95% CI, 0.09-0.88), and personal history of venous
thromboembolism (VTE) (OR, 0.36; 95% CI, 0.14-0.92) were negatively associated as
independent predictors of favorable (mRS = 0-1) outcome at follow-up. Conclusions
Most patients with a first CVT had complete or partial recanalization at follow
up. Recanalization was independently associated with a favorable neurological
outcome.
PMID- 29341412
TI - Three-dimensional neuromelanin-sensitive magnetic resonance imaging of the
substantia nigra in Parkinson's disease.
AB - BACKGROUND AND PURPOSE: The aim was to investigate the diagnostic utility of
signal intensity measurement of the substantia nigra pars compacta (SNc) using
three-dimensional (3D) neuromelanin-sensitive magnetic resonance imaging (MRI),
for discrimination of patients with Parkinson's disease (PD) from healthy
controls. METHODS: T1-weighted neuromelanin-sensitive images of 16 patients with
PD and 15 controls were quantitatively analyzed by placing circular 10 mm2
regions of interest over the central and lateral parts of the bilateral SNc and
anterior to the cerebral aqueduct at three levels of the midbrain. Signal
intensities and contrast ratios (CRs) were calculated, after which significant
differences, correlations, sensitivity and specificity were calculated. RESULTS:
The CRs of the central and lateral SNc were significantly lower in patients with
PD. Lateral CRs were lower than the central CRs in both groups and significantly
correlated with duration of illness. CRs of central and lateral parts of the SNc
also correlated with the Unified Parkinson's Disease Rating Scale III OFF state
scores. Receiver operating characteristic analysis revealed lateral CRs to be
more sensitive and central CRs to be more specific for the discrimination of
patients with PD from controls. CONCLUSIONS: Contrast ratio analysis of the SNc
using 3D neuromelanin-sensitive MRI may serve as a quick and accurate tool to
discern between patients with PD and healthy controls.
PMID- 29341413
TI - Effects of health insurance coverage on risky behaviors.
AB - Prior to implementation of the Patient Protection and Affordable Care Act,
dependent health insurance coverage was typically available only for young adults
under the age of 19. As of September 2010, the Affordable Care Act extended
dependent health insurance coverage to include young adults up to the age of 26.
I use the National Health Interview Survey for the sample period from 2011 to
2013 to analyze the causal relationship between the expansion of dependent
coverage and risky behaviors including smoking and drinking as well as preventive
care. I employ a regression discontinuity design to estimate the causal effect of
health insurance coverage and overcome the endogeneity problem between insurance
status and risky behaviors. When young adults become 26 years old, they are 7 to
10 percentage points more likely to lose health insurance than young adults under
the age of 26. Although young adults over the age of 26 are generally aged out of
insurance coverage, presence or absence of health insurance does not affect their
smoking and drinking behaviors and their access to preventive care.
PMID- 29341414
TI - Post-translational incorporation of 3,4-dihydroxyphenylalanine into the C
terminus of alpha-tubulin in living cells.
AB - The C-terminal tyrosine (Tyr) of the alpha-tubulin chain is subjected to post
translational removal and readdition in a process termed the
"detyrosination/tyrosination cycle". We showed in previous studies using soluble
rat brain extracts that l-3,4-dihydroxyphenylalanine (l-Dopa) is incorporated
into the same site as Tyr. We now demonstrate that l-Dopa incorporation into
tubulin also occurs in living cells. We detected such incorporation by
determining the "tyrosination state" of tubulin before and after incubation of
cells in the presence of l-Dopa. The presence of a tubulin isospecies following l
Dopa incubation that was not recognized by antibodies specific to Tyr- and deTyr
tubulin was presumed to reflect formation of Dopa-tubulin. l-Dopa was identified
by HPLC as the C-terminal compound bound to alpha-tubulin. l-Dopa incorporation
into tubulin was observed in Neuro 2A cells and several other cell lines, and was
not due to de novo protein biosynthesis. Dopa-tubulin had microtubule-forming
capability similar to that of Tyr- and deTyr-tubulin. l-Dopa incorporation into
tubulin did not notably alter cell viability, morphology, or proliferation rate.
CAD cells (a neuron-like cell line derived from mouse brain) are easily cultured
under differentiating and nondifferentiating conditions, and can be treated with
l-Dopa. Treatment of CAD cells with l-Dopa and consequent increase in l-Dopa
tubulin resulted in reduction of microtubule dynamics in neurite-like processes.
PMID- 29341415
TI - Operational sex ratio predicts the opportunity and direction of sexual selection
across animals.
AB - The operational sex ratio (OSR) has long been assumed to be a key ecological
factor determining the opportunity and direction of sexual selection. However,
recent theoretical work has challenged this view, arguing that a biased OSR does
not necessarily result in greater monopolisation of mates and therefore stronger
sexual selection in the mate-limited sex. Hence, the role of the OSR for shaping
animal mating systems remains a conundrum in sexual selection research. Here we
took a meta-analytic approach to test whether OSR explains interspecific
variation in sexual selection metrics across a broad range of animal taxa. Our
results demonstrate that the OSR predicts the opportunity for sexual selection in
males and the direction of sexual selection in terms of sex differences in both
the opportunity for sexual selection and the Bateman gradient (i.e. the selection
differential of mating success), as predicted by classic theory.
PMID- 29341416
TI - Resveratrol Influences Pancreatic Islets by Opposing Effects on Electrical
Activity and Insulin Release.
AB - SCOPE: Resveratrol is suggested to improve glycemic control by activation of
sirtuin 1 (SIRT1) and has already been tested clinically. Our investigation
characterizes the targets of resveratrol in pancreatic beta cells and their
contribution to short- and long-term effects on insulin secretion. METHODS AND
RESULTS: Islets or beta cells are isolated from C57BL/6N mice. Electrophysiology
is performed with microelectrode arrays and patch-clamp technique, insulin
secretion and content are determined by radioimmunoassay, cAMP is measured by
enzyme-linked immunosorbent assay, and cytosolic Ca2+ concentration by
fluorescence methods. Resveratrol (25 MUmol L-1 ) elevates [Ca2+ ]c and
potentiates glucose-stimulated insulin secretion. These effects are associated
with increased intracellular cAMP and are sensitive to the SIRT1 blocker Ex-527.
Inhibition of EPAC1 by CE3F4 also abolishes the stimulatory effect of
resveratrol. The underlying mechanism does not involve membrane depolarization as
resveratrol even reduces electrical activity despite blocking KATP channels.
Importantly, after prolonged exposure to resveratrol (14 days), the beneficial
influence of the polyphenol on insulin release is lost. CONCLUSION: Resveratrol
addresses multiple targets in pancreatic islets. Potentiation of insulin
secretion is mediated by SIRT1-dependent activation of cAMP/EPAC1. Considering
resveratrol as therapeutic supplement for patients with type 2 diabetes mellitus,
the inhibitory influence on electrical excitability attenuates positive effects.
PMID- 29341417
TI - Synthesis and Characterization of Photoactivatable Doxycycline Analogues Bearing
Two-Photon-Sensitive Photoremovable Groups Suitable for Light-Induced Gene
Expression.
AB - We report the synthesis and photolytic properties of caged 9-aminodoxycycline
derivatives modified with 2-{4'-bis-[2-(2methoxyethoxy)ethyl]-4-nitrobiphenyl-3
yl}prop-1-oxy (EANBP) and PEG7-ylated (7-diethylamino-2-oxo-2H-chromen-4
yl)methyl (PEG7-DEACM) groups. 9-Aminodoxycycline is a tetracycline analogue
capable of activating transcription through the inducible TetOn transgene
expression system and can be regioselectively coupled to two-photon-sensitive
photo-removable protecting groups by carbamoylation. The EANBP-based caged 9
aminodoxycycline showed complex photochemical reactions but did release 10 % of 9
aminodoxycycline. However, 9-(PEG7-DEACMamino)doxycycline exhibited excellent
photolysis efficiency at 405 nm with quantitative release of 9-aminodoxycycline
and a 0.21 uncaging quantum yield. Thanks to the good two-photon sensitivity of
the DEACM chromophore, 9-aminodoxycycline release by two-photon photolysis is
possible, with calculated action cross-sections of up to 4.0 GM at 740 nm.
Therefore, 9-(PEG7-DEACMamino)doxycycline represents a very attractive tool for
the development of a light-induced gene expression method in living cells.
PMID- 29341418
TI - Hand-held, clinical dual mode ultrasound - photoacoustic imaging of rat urinary
bladder and its applications.
AB - Urinary bladder imaging is critical to diagnose urinary tract disorders, and
bladder cancer. There is a great need for safe, non-invasive, and sensitive
imaging technique which enables bladder imaging. Photoacoustic imaging is a
rapidly growing imaging technique for various biological applications. It can be
combined with clinical ultrasound imaging system for hand-held, dual modal
ultrasound-photoacoustic real-time imaging. Structural (bladder wall) and
functional (accretion of nanoparticles) bladder imaging is shown here with
combined ultrasound and photoacoustic imaging in rats. Photoacoustic images of
bladder wall is shown using black ink as the contrast agent. Chicken tissues were
stacked on the abdomen of the animal to demonstrate the feasibility of
photoacoustic imaging till a depth of 2 cm. Also, the feasibility of
photoacoustic imaging for a common bladder disorder, vesicoureteral reflux is
studied using urinary tract mimicking phantom. It is also shown that a clinical
ultrasound system can be used for photoacoustic imaging of non-invasive clearance
study of gold nanorods from circulation by monitoring the gradual accumulation of
the gold nanorods in the bladder. The time taken for accumulation of nanorods in
the bladder can be used as an indicator of the clearance rate of the nanoparticle
circulation from the body.
PMID- 29341419
TI - Fatty liver index predicts incident diabetes in a Japanese general population
with and without impaired fasting glucose.
AB - AIM: Fatty liver is associated with the development of diabetes. However, to our
knowledge, no study has examined the relationship between the fatty liver index
(FLI), calculated scores of hepatic steatosis, and the development of diabetes
among individuals without impaired fasting glucose (IFG). We aimed to examine
whether FLI predicts the development of diabetes in individuals with and without
IFG in a Japanese general population. METHODS: We selected 1498 men and 2941
women who participated in Specific Health Checkups in Japan. We divided all
participants into six groups according to tertiles of FLI (low, moderate, and
high) and the presence or absence of IFG, by sex. We calculated hazard ratios for
incident diabetes for each group using a Cox proportional hazard model, adjusting
for potential confounders. RESULTS: During a mean follow-up period of 3.0 years,
176 cases of diabetes in men and 320 cases in women were identified. Compared
with the low FLI group without IFG, the high FLI group without IFG was
significantly associated with incident diabetes in both men (hazard ratio, 1.90;
95% confidence interval, 1.08-3.36) and women (hazard ratio, 1.72; 95% confidence
interval, 1.18-2.51). All IFG groups were significantly associated with incident
diabetes regardless of FLI levels. CONCLUSIONS: Our results showed that FLI is
associated with the development of diabetes regardless of sex and the presence or
absence of IFG, and that it may be a useful predictor of future risk of incident
diabetes even in individuals without IFG.
PMID- 29341420
TI - Transgenic mice specifically expressing amphiregulin in white adipose tissue
showed less adipose tissue mass.
AB - To determine adipocytokines that play a regulatory role during obesity
development, we explored the genes that encode growth factors and investigated
the physiological functions for adipose tissue development. Here, we isolated
amphiregulin (Areg) gene whose expression was significantly up-regulated in obese
adipose tissues. Areg mRNA level was positively correlated with macrophage marker
gene expression in adipose tissues in vivo. Unexpectedly, Areg transgenic mice
showed less adipose tissue mass with increased mRNA expression levels of Tnf
alpha and peroxisome proliferator-activated receptor gamma coactivator 1alpha
(Pgc-1alpha) and delayed white adipose tissue development during the convalescent
stage in a dextran sodium sulfate-induced colitis model. This study showed that
Areg mRNA expression was significantly up-regulated in obese adipose tissues and
over-expression of Areg in white adipose tissue caused less adipose tissue mass.
PMID- 29341421
TI - A Stable Room-Temperature Luminescent Biphenylmethyl Radical.
AB - There is only one family of room-temperature luminescent radicals, the
triphenylmethyl radicals, to date. Herein, we synthesize a new stable room
temperature luminescent radical, (N-carbazolyl)bis(2,4,6-tirchlorophenyl)methyl
radical (CzBTM), which has improved properties compared to the triphenylmethyl
radicals. X-ray crystallography, electron paramagnetic resonance spectroscopy,
and magnetic susceptibility measurements confirmed the radical structure. CzBTM
shows room-temperature deep-red to near-infrared emission in various solutions.
Both thermal and photo stability were significantly enhanced by the replacement
of trichlorobenzene by the carbazole moiety. The electroluminescence results of
CzBTM verify its potential application to circumvent the problem of triplet
harvesting in traditional fluorescent OLEDs. A new family of stable luminescent
radicals based on CzBTM is anticipated.
PMID- 29341422
TI - Synthesis and luminescence properties of cubic-shaped Ca1-x TiO3 :Eu3+ particles.
AB - In this article Ca1-x TiO3 :xEu3+ single crystalline particles with a cubic
morphology and average size of 248 to 815 nm were synthesized by a solvothermal
method. The structural and optical properties of the Ca1-x TiO3 :xEu3+ cubes were
investigated, the formation mechanism of the cubes were analyzed and discussed,
and the influence of Eu doping content and cubic size on the photoluminescence
were examined. The differences in the photoluminescence between Ca1-x TiO3 :xEu3+
cubic crystals and nanoparticles was analyzed. It was found that an addition of a
small amount of water can substantially reduce the size of the cubes. An obvious
red emission band centered at 615 nm was observed under the excitation at 395 nm
for the cubes. Our results demonstrate CaTiO3 cubes are good host materials for
designing red phosphors.
PMID- 29341423
TI - Variable immune deficiency related to deletion size in chromosome 22q11.2
deletion syndrome.
AB - The clinical features of 22q11.2 deletion syndrome include virtually every organ
of the body. This review will focus on the immune system and the differences
related to deletion breakpoints. A hypoplastic thymus was one of the first
features described in this syndrome and low T cell counts, as a consequence of
thymic hypoplasia, are the most commonly described immunologic feature. These are
most prominently seen in early childhood and can be associated with increased
persistence of viruses. Later in life, evidence of T cell exhaustion may be seen
and secondary deficiencies of antibody function have been described. The
relationship of the immunodeficiency to the deletion breakpoints has been
understudied due to the infrequent analysis of people carrying smaller deletions.
This manuscript will review the immune deficiency in 22q11.2 deletion syndrome
and describe differences in the T cell counts related to the deletion
breakpoints. Distal, non-TBX1 inclusive deletions, were found to be associated
with better T cell counts. Another new finding is the relative preservation of T
cell counts in those patients with a 22q11.2 duplication.
PMID- 29341424
TI - Fetal ultrasonographic findings including cerebral hyperechogenicity in a patient
with non-lethal form of Raine syndrome.
AB - Raine syndrome is a rare osteosclerotic bone dysplasia characterized by
craniofacial anomalies and intracranial calcification. Most patients with Raine
syndrome are of Arab ancestry and die during the neonatal period. We herein
report a Japanese patient with non-lethal Raine syndrome who presented with
characteristic cerebral hyperechogenicity and a hypoplastic nose by fetal
ultrasonography. She was admitted to the NICU due to pyriform aperture stenosis.
Craniofacial abnormalities, intracranial calcification, osteosclerosis,
chondrodysplasia punctata, and a mutation of FAM20C was identified. She was
subsequently discharged without surgical intervention and is now 2 years old with
mild neurodevelopmental delays. Images of cerebral hyperechogenicity by fetal
ultrasonography in a non-lethal case were described herein for the first time.
This patient represents a rare occurrence of a child with Raine syndrome born to
Japanese parents and confirms that this syndrome is not always lethal. Even if
Raine syndrome is suspected in a fetus due to cerebral hyperechogenicity and a
hypoplastic nose, cerebral hyperechogenicity without pulmonary hypoplasia does
not always predict lethality or severe neurodevelopmental delays. The information
provided herein will be useful for prenatal counseling.
PMID- 29341425
TI - Synthesis of novel Dy3+ activated Ba2 CaZn2 Si6 O17 phosphors for white light
emitting diodes.
AB - Dysprosium ion (Dy3+ ) activated Ba2 CaZn2 Si6 O17 phosphors were synthesized
using high temperature solid-state reaction method. Powder X-ray diffraction
(PXRD) analysis confirmed the phase formation of the as-prepared phosphors.
Scanning electron microscopy (SEM) analysis disclosed an agglomeration of
particles with an irregular morphology. Under 350 nm excitation, the emission
spectrum of Dy3+ ions showed bands at 481 nm (blue), 577 nm (yellow) and 674 nm
(red). The influence of the Dy3+ concentration on its emission intensity was
investigated. The optimum concentration of Dy3+ ions in the Ba2 CaZn2 Si6 O17
:Dy3+ phosphors were found to be x = 0.06. The critical energy transfer distance
was calculated. The fluorescence lifetime was also determined for Ba2 CaZn2 Si6
O17 :0.06Dy3+ . The Commission International deI'Eclairage (CIE) chromaticity
coordinates of the phosphor were calculated to be x = 0.304, y = 0.382. The
activation energy for the thermal quenching was calculated to be 0.168 eV. These
results indicated that the Ba2 CaZn2 Si6 O17 :Dy3+ phosphor might be a potential
candidate for near ultraviolet (NUV)-based white light-emitting diodes.
PMID- 29341426
TI - Biomechanical, histological, and computed X-ray tomographic analyses of
hydroxyapatite coated PEEK implants in an extended healing model in rabbit.
AB - A nanosized hydroxyapatite (HA) modification on polyetheretherketone (PEEK) using
a novel spin coating technique was investigated in a rabbit model. Spin coating
technique creates a 20-40 nm thick layer of nanosized HA particles with similar
shape, size, and crystallinity as human bone. Some implants were designed with a
perforating hole in the apical region to mimic a fusion chamber of a spinal
implant. The coating nano-structures were assessed using a scanning electron
microscope. The in vivo response to HA-PEEK was compared to untreated PEEK with
respect to removal torque, histomorphometry, and computed microtomography. The HA
coated and pure PEEK implants were inserted in the tibia and femur bone according
to simple randomization. The rabbits were sacrificed 20 weeks after implantation.
Removal torque analysis showed significantly higher values for HA-PEEK.
Qualitative histological evaluation revealed an intimate contact between PEEK and
the bone at the threads and perforated hole. Histomorphometric assessment showed
higher bone-implant and bone area values for HA-PEEK but without statistical
significance. The effect of the HA coating showed most prominent effect in the
removal torque which may be correlated to an alteration in the bone quality
around the HA-PEEK implants. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res
Part A: 106A: 1440-1447, 2018.
PMID- 29341427
TI - LC/MS-based Intact IgG and Released Glycan Analysis for Bioprocessing
Applications.
AB - Robust plate based antibody glycan analysis platforms are urgently needed for
biopharmaceutical development and manufacturing as well as for clinical biomarker
research. A 96-well plate based workflow has been developed to analyze both
intact IgG antibodies and released N-glycans using an Orbitrap Fusion Mass
Spectrometer and an LC/MS method on the Waters UNIFI platform. Here, such a
workflow including protein A purification, PNGaseF digestion, 2-AB labeling, and
SPE clean-up is described. The measured IgG glycan profile is consistent with
that obtained from non-plate based method and commercial kit and has the
advantage of less hands-on time. Also the application of the workflow in cell
culture monitoring and clonal selection work is demonstrated. Apart from checking
the major glycan structure changes among clones, post translational modifications
(PTMs) such as C-terminal lysine residue clipping and N-terminal pyroglutamic
acid formation can also be deduced from the workflow.
PMID- 29341428
TI - Epigenetic Silencing of TAP1 in Aldefluor+ Breast Cancer Stem Cells Contributes
to Their Enhanced Immune Evasion.
AB - Avoiding detection and destruction by immune cells is key for tumor initiation
and progression. The important role of cancer stem cells (CSCs) in tumor
initiation has been well established, yet their ability to evade immune detection
and targeting is only partly understood. To investigate the ability of breast
CSCs to evade immune detection, we identified a highly tumorigenic population in
a spontaneous murine mammary tumor based on increased aldehyde dehydrogenase
activity. We performed tumor growth studies in immunocompetent and
immunocompromised mice. In immunocompetent mice, growth of the spontaneous
mammary tumor was restricted; however, the Aldefluor+ population was expanded,
suggesting inherent resistance mechanisms. Gene expression analysis of the sorted
tumor cells revealed that the Aldefluor+ tumor cells has decreased expression of
transporter associated with antigen processing (TAP) genes and co-stimulatory
molecule CD80, which would decrease susceptibility to T cells. Similarly, the
Aldefluor+ population of patient tumors and 4T1 murine mammary cells had
decreased expression of TAP and co-stimulatory molecule genes. In contrast,
breast CSCs identified by CD44+ CD24- do not have decreased expression of these
genes, but do have increased expression of C-X-C chemokine receptor type 4.
Decitabine treatment and bisulfite pyrosequencing suggests that DNA
hypermethylation contributes to decreased TAP gene expression in Aldefluor+ CSCs.
TAP1 knockdown resulted in increased tumor growth of 4T1 cells in immunocompetent
mice. Together, this suggests immune evasion mechanisms in breast CSCs are marker
specific and epigenetic silencing of TAP1 in Aldefluor+ breast CSCs contributes
to their enhanced survival under immune pressure. Stem Cells 2018;36:641-654.
PMID- 29341430
TI - Tuberculosis vaccines: Opportunities and challenges.
AB - Tuberculosis (TB) is a serious disease around the world. Bacillus Calmette-Guerin
(BCG) is the only TB vaccine licensed for use in human beings, and is effective
in protecting infants and children against severe miliary and meningeal TB.
However, BCG's protective efficacy is variable in adults. Novel TB vaccine
candidates being developed include whole-cell vaccines (recombinant BCG (rBCG),
attenuated Mycobacterium tuberculosis, killed M. tuberculosis or Mycobacterium
vaccae), adjuvanted protein subunit vaccines, viral vector-delivered subunit
vaccines, plasmid DNA vaccines, RNA-based vaccines etc. At least 12 novel TB
vaccine candidates are now in clinical trials, including killed M. vaccae, rBCG
DeltaureC::hly, adjuvanted fusion proteins M72 and H56 and viral vectored MVA85A.
Unfortunately, in TB, there are no correlates of vaccine-induced protection,
although cell-mediated immune responses such as interferon-gamma (IFN-gamma)
production are widely used to assess vaccine's immunogenicity. Recent studies
suggested that central memory T cells and local secreted IgA correlated with
protection against TB disease. Clinical TB vaccine efficacy trials should invest
in identifying correlates of protection, and evaluate new TB biomarkers emerging
from human and animal studies. Accumulating new knowledge on M. tuberculosis
antigens and immune profiles correlating with protection or disease risk will be
of great help in designing next generation of TB vaccines.
PMID- 29341431
TI - Risk of infantile hemangiomas in the offspring of women with autoimmune disease
and the pathogenic implications of these lesions.
AB - The purpose of this study was to analyze the risk of maternal autoimmune disease
or associated treatments on infantile hemangiomas (IHs), a common benign vascular
tumor in infants, and to better understand how maternal chronic inflammation may
play a factor in the pathogenesis of these lesions. Eligible women from the
United States and Canada who enrolled before 19 weeks' gestation and delivered at
least one live born infant were recruited as part of the Organization of
Teratology Information Specialists (OTIS) Autoimmune Disease in Pregnancy Project
from 2004-2013. A total of 51/969 (5.3%) and 8/240 (3.3%) infants with IH were
born to mothers with and without autoimmune disease, respectively (OR 1.61;
95%CI, 0.75-.44). The presence of ulcerative colitis (UC) in the mother was
significantly associated with IH in the child (OR 3.46; 95%CI, 1.29-9.26). The
five largest IH occurred within the autoimmune disease cohort and to women taking
a biologic medication. These results imply that UC may be a risk factor for IH
development, and that chronic inflammation may influence the development of these
lesions. This potential link between IH and autoimmune disease warrants further
investigation.
PMID- 29341433
TI - Corrigendum.
PMID- 29341432
TI - Duck "beak atrophy and dwarfism syndrome" disease complex: Interplay of novel
goose parvovirus-related virus and duck circovirus?
AB - As a newly emerged infectious disease, duck "beak atrophy and dwarfism syndrome
(BADS)" disease has caused huge economic losses to waterfowl industry in China
since 2015. Novel goose parvovirus-related virus (NGPV) is believed the main
pathogen of BADS disease; however, BADS is rarely reproduced by infecting ducks
with NGPV alone. As avian circovirus infection causes clinical symptoms similar
to BADS, duck circovirus (DuCV) is suspected the minor pathogen of BADS disease.
In this study, an investigation was carried out to determine the coinfection of
NGPV and DuCV in duck embryos and in ducks with BADS disease. According to our
study, the coinfection of emerging NGPV and DuCV was prevalent in East China
(Shandong, Jiangsu and Anhui province) and could be vertical transmitted,
indicating their cooperative roles in duck BADS disease.
PMID- 29341429
TI - Trans-acting translational regulatory RNA binding proteins.
AB - The canonical molecular machinery required for global mRNA translation and its
control has been well defined, with distinct sets of proteins involved in the
processes of translation initiation, elongation and termination. Additionally,
noncanonical, trans-acting regulatory RNA-binding proteins (RBPs) are necessary
to provide mRNA-specific translation, and these interact with 5' and 3'
untranslated regions and coding regions of mRNA to regulate ribosome recruitment
and transit. Recently it has also been demonstrated that trans-acting ribosomal
proteins direct the translation of specific mRNAs. Importantly, it has been shown
that subsets of RBPs often work in concert, forming distinct regulatory complexes
upon different cellular perturbation, creating an RBP combinatorial code, which
through the translation of specific subsets of mRNAs, dictate cell fate. With the
development of new methodologies, a plethora of novel RNA binding proteins have
recently been identified, although the function of many of these proteins within
mRNA translation is unknown. In this review we will discuss these methodologies
and their shortcomings when applied to the study of translation, which need to be
addressed to enable a better understanding of trans-acting translational
regulatory proteins. Moreover, we discuss the protein domains that are
responsible for RNA binding as well as the RNA motifs to which they bind, and the
role of trans-acting ribosomal proteins in directing the translation of specific
mRNAs. This article is categorized under: RNA Interactions with Proteins and
Other Molecules > RNA-Protein Complexes Translation > Translation Regulation
Translation > Translation Mechanisms.
PMID- 29341434
TI - Recombinant collagen scaffolds as substrates for human neural stem/progenitor
cells.
AB - Adhesion to the microenvironment profoundly affects stem cell functions,
including proliferation and differentiation, and understanding the interaction of
stem cells with the microenvironment is important for controlling their behavior.
In this study, we investigated the effects of the integrin binding epitopes
GFOGER and IKVAV (natively present in collagen I and laminin, respectively) on
human neural stem/progenitor cells (hNSPCs). To test the specificity of these
epitopes, GFOGER or IKVAV were placed within the context of recombinant triple
helical collagen III engineered to be devoid of native integrin binding sites.
HNSPCs adhered to collagen that presented GFOGER as the sole integrin-binding
site, but not to IKVAV-containing collagen. For the GFOGER-containing collagens,
antibodies against the beta1 integrin subunit prevented cellular adhesion,
antibodies against the alpha1 subunit reduced cell adhesion, and antibodies
against alpha2 or alpha3 subunits had no significant effect. These results
indicate that hNSPCs primarily interact with GFOGER through the alpha1beta1
integrin heterodimer. These GFOGER-presenting collagen variants also supported
differentiation of hNSPCs into neurons and astrocytes. Our findings show, for the
first time, that hNSPCs can bind to the GFOGER sequence, and they provide
motivation to develop hydrogels formed from recombinant collagen variants as a
cell delivery scaffold. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part
A: 106A: 1363-1372, 2018.
PMID- 29341435
TI - Bifunctional Fluorescent Probe for Sequential Sensing of Thiols and Primary
Aliphatic Amines in Distinct Fluorescence Channels.
AB - Thiols and primary aliphatic amines (PAA) are ubiquitous and extremely important
species in biological systems. They perform significant interplaying roles in
complex biological events. A single fluorescent probe differentiating both thiols
and PAA can contribute to understanding the intrinsic inter-relationship of
thiols and PAA in biological processes. Herein, we rationally constructed the
first fluorescent probe that can respond to thiols and PAA in different
fluorescence channels. The probe exhibited a high selectivity and sensitivity to
thiols and PAA. In addition, it displayed sequential sensing ability when the
thiols and PAA coexisted. The application experiments indicated that the probe
can be used for sensing thiols and PAA in human blood serum. Moreover, the
fluorescence imaging of endogenous thiols and PAA as well as antihypertensive
drugs captopril and amlodipine in living cells were successfully conducted.
PMID- 29341436
TI - A novel near-infrared fluorescent probe for monitoring cyclooxygenase-2 in
inflammation and tumor.
AB - Targeting cyclooxygenase-2 (COX-2) for molecular imaging is an attractive
approach applicable for its overexpression in inflammation and many malignancies.
Herein, for monitoring COX-2, we synthesize a specific COX-2 probe celecoxib-MPA
probe (CMP), based on celecoxib and a water-soluble near-infrared dye dye ICG-Der
02 (MPA). Its high affinity for binding to COX-2 is verified by molecular
docking, dynamics simulation and inhibition assay. At cellular level, CMP
selectively accumulates in cytoplasm of COX-2-positive cells. in vivo assays,
probe guided-imaging in inflamed or cancerous tissues confirms that CMP can bind
to the locally endogenic COX-2 and exhibit intense fluorescence. Importantly, we
further prove the targeting specificity of CMP as the fluorescence is
significantly reduced by blocking COX-2 active site through preinjection with
celecoxib. The results suggest that the probe CMP, with favorable hydrophilic
property, good biocompatibility, long-term observation, excellent targeting
ability and optical imaging capability, could serve as a promising probe for real
time monitoring COX-2 in inflammation and tumor.
PMID- 29341437
TI - Phenotypic heterogeneity of ZMPSTE24 deficiency.
AB - A 4-year-old girl was referred to the Undiagnosed Diseases Network with a history
of short stature, thin and translucent skin, macrocephaly, small hands, and
camptodactyly. She had been diagnosed with possible Hallerman-Streiff syndrome.
Her evaluation showed that she was mosaic for uniparental isodisomy of chromosome
1, which harbored a pathogenic c.1077dupT variant in ZMPSTE24 which predicts
p.(Leu362fsX18). ZMPSTE24 is a zinc metalloproteinase that is involved in
processing farnesylated proteins and pathogenic ZMPSTE24 variants cause
accumulation of abnormal farnesylated forms of prelamin A. This, in turn, causes
a spectrum of disease severity which is based on enzyme activity. The current
patient has an intermediate form, which is a genocopy of severe Progeria.
PMID- 29341440
TI - Response to Hostetler.
PMID- 29341439
TI - Therapeutic benefits of CD90-negative cardiac stromal cells in rats with a 30-day
chronic infarct.
AB - Cardiac stromal cells (CSCs) can be derived from explant cultures, and a subgroup
of these cells is viewed as cardiac mesenchymal stem cells due to their
expression of CD90. Here, we sought to determine the therapeutic potential of
CD90-positive and CD90-negative CSCs in a rat model of chronic myocardial
infarction. We obtain CD90-positive and CD90-negative fractions of CSCs from rat
myocardial tissue explant cultures by magnetically activated cell sorting. In
vitro, CD90-negative CSCs outperform CD90-positive CSCs in tube formation and
cardiomyocyte functional assays. In rats with a 30-day infarct, injection of CD90
negative CSCs augments cardiac function in the infarct in a way superior to that
from CD90-positive CSCs and unsorted CSCs. Histological analysis revealed that
CD90-negative CSCs increase vascularization in the infarct. Our results suggest
that CD90-negative CSCs could be a development candidate as a new cell therapy
product for chronic myocardial infarction.
PMID- 29341441
TI - Organic Microcrystal Vibronic Lasers with Full-Spectrum Tunable Output beyond the
Franck-Condon Principle.
AB - The very broad emission bands of organic semiconductor materials are, in theory,
suitable for achieving versatile solid-state lasers; however, most of organic
materials only lase at short wavelength corresponding to the 0-1 transition
governed by the Franck-Condon (FC) principle. A strategy is developed to overcome
the limit of FC principle for tailoring the output of microlasers over a wide
range based on the controlled vibronic emission of organic materials at
microcrystal state. For the first time, the output wavelength of organic lasers
is tailored across all vibronic (0-1, 0-2, 0-3, and even 0-4) bands spanning the
entire emission spectrum.
PMID- 29341438
TI - Natural antisense transcripts in diseases: From modes of action to targeted
therapies.
AB - Antisense transcription is a widespread phenomenon in mammalian genomes, leading
to production of RNAs molecules referred to as natural antisense transcripts
(NATs). NATs apply diverse transcriptional and post-transcriptional regulatory
mechanisms to carry out a wide variety of biological roles that are important for
the normal functioning of living cells, but their dysfunctions can be associated
with human diseases. In this review, we attempt to provide a molecular basis for
the involvement of NATs in the etiology of human disorders such as cancers and
neurodegenerative and cardiovascular diseases. We also discuss the pros and cons
of oligonucleotide-based therapies targeted against NATs, and we comment on state
of-the-art progress in this promising area of clinical research. WIREs RNA 2018,
9:e1461. doi: 10.1002/wrna.1461 This article is categorized under: RNA in Disease
and Development > RNA in Disease Regulatory RNAs/RNAi/Riboswitches > Regulatory
RNAs RNA Interactions with Proteins and Other Molecules > Small Molecule-RNA
Interactions.
PMID- 29341442
TI - Motivating influences and ability-based outcomes of dental hygiene baccalaureate
education in Canada.
AB - BACKGROUND: There is a scarcity of studies on Canadian baccalaureate dental
hygienists. As discussions about baccalaureate education for dental hygiene
continue on a national level, examining outcomes of earning a dental hygiene
degree is paramount. OBJECTIVE: To investigate the motivating reasons and ability
based outcomes of earning a Bachelor of Dental Science in Dental Hygiene (BDSc)
degree from the University of British Columbia (UBC), Canada. METHODS: UBC dental
hygiene entry-to-practice (ETP) and degree-completion (DC) graduates (n = 116;
32%) from 1994 to 2016 participated in an online mixed-methods survey. Survey
questions explored motivating reasons for pursuing dental hygiene degree
education and abilities gained during their degree. RESULTS: Primary reasons for
pursuing a degree were personal satisfaction (82%), increasing knowledge base
(82%), increasing employment opportunities (78%), status/recognition of a degree
(76%), accessing graduate education (68%) and improving critical thinking
abilities (61%). For DC graduates, abilities strengthened included enhanced
skills for appraising research (92%), enhanced critical thinking and problem
solving skills (90%), enhanced skills for retrieving scientific information (88%)
and increased value for lifelong learning (84%). Enhanced abilities positively
influenced client care in the areas of evidence-based decision-making,
communicating information to clients, and collaborating with other professionals.
Overall, 93% of respondents believe a baccalaureate degree should be the ETP
credential for dental hygiene because it enhances critical thinking and better
prepares graduates for diverse roles in society with more complex populations.
CONCLUSION: The results highlight the impact of baccalaureate education on dental
hygiene practice in Canada.
PMID- 29341443
TI - Stachyose Improves Inflammation through Modulating Gut Microbiota of High-Fat
Diet/Streptozotocin-Induced Type 2 Diabetes in Rats.
AB - SCOPE: The present study is undertaken to assess the effects of stachyose (STS)
on type 2 diabetes in rats and changes in the gut microbiota compared to
metformin (MET). METHODS AND RESULTS: The type 2 diabetic model is successfully
established via a high-fat diet /streptozotocin in Wistar rats, and STS or MET is
administered for 4 weeks. Blood is collected to analyze biochemical parameters,
pancreas for mRNA expression of related gene, and contents of colon for gut
microbiota. STS or MET decreases serum LPS, mRNA expression of IL-6, and tumor
necrosis factor-alpha (TNF-alpha). In addition, STS and MET show a similar
shifting of the structure of the gut microbiota and a selective enrichment of key
species. At the genus level, STS shows selective enrichment of
Phascolarctobacterium, Bilophila, Oscillospira, Turicibacter, and SMB5, but MET
demonstrates a selective effect on Sutterella, Prevotella, 02d06, and rc4. The
correlation analysis indicates that STS and MET decrease IL-6 and TNF-alpha and
increase Akt/PI3K expression, which are relative to key species of gut
microbiota. CONCLUSION: STS decreases pancreatic mRNA expression of IL-6 and TNF
alpha via key species of gut microbiota. The mechanism of this effect is similar
to that of MET.
PMID- 29341444
TI - Teaching clinical leadership to medical students.
PMID- 29341445
TI - Automated detection of preserved photoreceptor on optical coherence tomography in
choroideremia based on machine learning.
AB - Optical coherence tomography (OCT) can demonstrate early deterioration of the
photoreceptor integrity caused by inherited retinal degeneration diseases (IRDs).
A machine learning method based on random forests was developed to automatically
detect continuous areas of preserved ellipsoid zone structure (an easily
recognizable part of the photoreceptors on OCT) in 16 eyes of patients with
choroideremia (a type of IRD). Pseudopodial extensions protruding from the
preserved ellipsoid zone areas are detected separately by a local active contour
routine. The algorithm is implemented on en face images with minimum segmentation
requirements, only needing delineation of the Bruch's membrane, thus evading the
inaccuracies and technical challenges associated with automatic segmentation of
the ellipsoid zone in eyes with severe retinal degeneration.
PMID- 29341446
TI - Carboxytherapy for treatment of localized chronic plaque psoriasis: Clinical and
histopathologic evaluation.
AB - BACKGROUND: Multiple treatment options are introduced in treatment of chronic
localized plaque psoriasis but with poor adherence and poor patients'
satisfaction resulting in poor treatment outcome. OBJECTIVE: In this pilot study,
we investigated the safety and efficacy of carboxytherapy in treatment of chronic
localized plaque psoriasis. METHODS: Thirty adult patients with chronic localized
plaque psoriasis were enrolled in this study. The patients received
carboxytherapy injection once/week for 8 weeks. Patients were clinically and
histpathologically evaluated 2 weeks after the last treatment. Clinical response
was evaluated by investigator's global assessment, total sign score, and 5-point
scale for perilesional erythema. We performed 10-point visual analog scale for
patient's satisfaction, and side effects. Three months after the last session we
evaluate recurrence using 10-point scale. RESULTS: Carboxytherapy achieved
treatment success in 26.6% according to investigator's global assessment and
total sign score and 70% of the patients demonstrated absence of perilesional
erythema. Patients were satisfied with no reported side effects. Recurrence area
was within 1% -10% of the baseline area in 83.3% of the improved patients.
PMID- 29341447
TI - Anti-transcription intermediary factor 1gamma antibody titer correlates with
clinical symptoms in a patient with recurrent dermatomyositis associated with
ovarian cancer.
PMID- 29341448
TI - Beneficial actions of microbiota-derived tryptophan metabolites.
AB - Tryptophan is an important dietary amino acid and it is the precursor for 5
hydroxytryptamine synthesis in the nervous system and by enterochromaffin cells
in the gut mucosa. Tryptophan is also metabolized by enzymes in the gut mucosa
and also by enzymes produced by the gut microbiome. Diet and the microbiome can
contribute to metabolic disease in part by causing intestinal inflammation and
increased permeability. In this issue of Neurogastroenterology and Motility,
Jennis et al. test the hypothesis that indole tryptophan metabolites produced by
gut bacteria might be responsible for the anti-inflammatory and beneficial
metabolic effects of the gut microbiome and Roux-en-Y gastric bypass surgery for
weight loss by obese patients. The authors identified indole-3-propionic acid as
the beneficial metabolite. A review of the literature also revealed the
beneficial effects of tryptophan metabolites on diabetes and metabolic disease
and on inflammatory bowel disease. Taken together, these data highlight another
health benefit of the intestinal microbiome, which produces beneficial products
from dietary amino acids especially tryptophan.
PMID- 29341449
TI - Digging deeper: A holistic perspective of factors affecting soil organic carbon
sequestration in agroecosystems.
AB - The global magnitude (Pg) of soil organic carbon (SOC) is 677 to 0.3-m, 993 to
0.5-m, and 1,505 to 1-m depth. Thus, ~55% of SOC to 1-m lies below 0.3-m depth.
Soils of agroecosystems are depleted of their SOC stock and have a low use
efficiency of inputs of agronomic yield. This review is a collation and synthesis
of articles published in peer-reviewed journals. The rates of SOC sequestration
are scaled up to the global level by linear extrapolation. Soil C sink capacity
depends on depth, clay content and mineralogy, plant available water holding
capacity, nutrient reserves, landscape position, and the antecedent SOC stock.
Estimates of the historic depletion of SOC in world soils, 115-154 (average of
135) Pg C and equivalent to the technical potential or the maximum soil C sink
capacity, need to be improved. A positive soil C budget is created by increasing
the input of biomass-C to exceed the SOC losses by erosion and mineralization.
The global hotspots of SOC sequestration, soils which are farther from C
saturation, include eroded, degraded, desertified, and depleted soils. Ecosystems
where SOC sequestration is feasible include 4,900 Mha of agricultural land
including 332 Mha equipped for irrigation, 400 Mha of urban lands, and ~2,000 Mha
of degraded lands. The rate of SOC sequestration (Mg C ha-1 year-1 ) is 0.25-1.0
in croplands, 0.10-0.175 in pastures, 0.5-1.0 in permanent crops and urban lands,
0.3-0.7 in salt-affected and chemically degraded soils, 0.2-0.5 in physically
degraded and prone to water erosion, and 0.05-0.2 for those susceptible to wind
erosion. Global technical potential of SOC sequestration is 1.45-3.44 Pg C/year
(2.45 Pg C/year).
PMID- 29341450
TI - Characterization of a novel, papain-inducible murine model of eosinophilic
rhinosinusitis.
AB - BACKGROUND: Eosinophilic chronic rhinosinusitis (ECRS) is a disease characterized
by eosinophilic inflammatory infiltrate and a local type 2 cytokine milieu.
Current animal models fail to recapitulate many of the innate and adaptive
immunologic hallmarks of the disease, thus hindering the development of effective
therapeutics. In the present study, mice were exposed intranasally to the
cysteine protease papain, which shares functional similarities with parasitic
proteases and aeroallergens, to generate a rapidly inducible murine model of
eosinophilic rhinosinusitis. METHODS: C57BL/6 mice were intranasally instilled
with 20 MUg papain or heat-inactivated papain (HP) on days 0-2 and days 7-10, and
then euthanized on day 11. Nasal lavage fluid (NALF) was analyzed to quantify
eosinophils and inflammatory cytokine secretion. Sinonasal tissue was sectioned
and stained for goblet cells or homogenized to analyze cytokine levels. Serum
samples were assayed for immunoglobulin E (IgE) by enzyme-linked immunoassay.
Sinonasal mucosal tissue was dissociated and analyzed by flow cytometry. RESULTS:
Compared with HP treatment, papain induced significant eosinophilia in NALF,
goblet cell hyperplasia, innate and adaptive immune cell infiltration, type 2
cytokine production, and IgE responses. Flow cytometric analysis of sinonasal
tissues revealed significant inflammatory cell infiltration and interleukin-13
producing cell populations. CONCLUSION: In this study, we demonstrated that the
cysteine protease papain induces allergic sinonasal eosinophilic rhinosinusitis
and resembles T-helper 2 cell inflammation and innate immune characteristics of
ECRS. This model permits further study into the molecular mechanisms underlying
ECRS pathology and provides a model system for the evaluation of potential
pharmacologic interventions.
PMID- 29341451
TI - Exophytic sinonasal papillomas and nasal florid papillomatosis: A retrospective
study.
AB - BACKGROUND: Sinonasal exophytic papillomas are rare. The multifocal form, florid
papillomatosis, has not been yet described in literature. We report on the
clinical features and the management of the different forms of exophytic
papilloma. METHODS: A retrospective study was conducted that included all
patients with exophytic papilloma treated in our center over the past 12 years.
We recorded clinical presentation, treatments, recurrences, pathology (p16
expression and human papillomavirus [HPV] status). RESULTS: We included 13
patients with a mean follow-up of 5 years. The main location of exophytic
papilloma was the anterior part of the septum. Lesions were multifocal in 3
patients corresponding to florid papillomatosis. The main treatment was surgery.
Cases of HPV-11 or HPV-6 were present in all forms of exophytic papilloma
(dysplasia in 4 cases). Late recurrences occurred in 3 patients (2 patients with
florid papillomatosis) over a period of 3 years. CONCLUSION: Exophytic papilloma
has 2 clinical presentations: localized and diffuse. Patients with florid
papillomatosis should be monitored closely as recurrence seems to be frequent.
PMID- 29341452
TI - Contribution of MLH1 constitutional methylation for Lynch syndrome diagnosis in
patients with tumor MLH1 downregulation.
AB - Constitutional epimutation of the two major mismatch repair genes, MLH1 and MSH2,
has been identified as an alternative mechanism that predisposes to the
development of Lynch syndrome. In the present work, we aimed to investigate the
prevalence of MLH1 constitutional methylation in colorectal cancer (CRC) patients
with abnormal expression of the MLH1 protein in their tumors. In a series of 38
patients who met clinical criteria for Lynch syndrome genetic testing, with loss
of MLH1 expression in the tumor and with no germline mutations in the MLH1 gene
(35/38) or with tumors presenting the BRAF p.Val600Glu mutation (3/38), we
screened for constitutional methylation of the MLH1 gene promoter using
methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA)
in various biological samples. We found four (4/38; 10.5%) patients with
constitutional methylation in the MLH1 gene promoter. RNA studies demonstrated
decreased MLH1 expression in the cases with constitutional methylation when
compared with controls. We could infer the mosaic nature of MLH1 constitutional
hypermethylation in tissues originated from different embryonic germ layers, and
in one family we could show that it occurred de novo. We conclude that
constitutional MLH1 methylation occurs in a significant proportion of patients
who have loss of MLH1 protein expression in their tumors and no MLH1 pathogenic
germline mutation. Furthermore, we provide evidence that MLH1 constitutional
hypermethylation is the molecular mechanism behind about 3% of Lynch syndrome
families diagnosed in our institution, especially in patients with early onset or
multiple primary tumors without significant family history.
PMID- 29341453
TI - Mechanism underlying the negative effect of prostate volume on the outcome of
extensive transperineal ultrasound-guided template prostate biopsy.
AB - Previous studies have indicated a possible relationship between increased
prostate volume (PV) and decreased biopsy yield, although the mechanism involved
is unclear. We evaluated 1650 patients who underwent template biopsy. The
distribution of 993 cancer lesions in 302 prostatectomy specimens was compared
with the biopsy data to determine whether each lesion was detected. A receiver
operating characteristic (ROC) model was used to determine the diagnostic
accuracy of prostate-specific antigen (PSA) and related markers. A medical record
number (MRN) was used as a negative control. The cancer positive rate did not
change as PSA increased in patients with PV >=50 mL (P = 0.466), although it
increased as PSA increased in patients with PV<50 mL (P = 0.001). The detection
rate of cancer lesions decreased as the diameter of the lesions decreased (P =
0.018), but remained unchanged with respect to PV. The diameters of the maximum
lesions in patients with PV >= 50 mL were significantly smaller than those in
patients with PV<50 mL (P = 0.003). In patients with PV >= 50 mL, the areas under
the ROC curves for PSA-related markers did not differ significantly from that for
MRN, although they were significantly greater than that for MRN in patients with
PV<50 mL (P < 0.001). These results suggest that an increase in PV is associated
with a decrease in size and detectability of cancer lesions resulting in a
decrease in biopsy yield. Loss of diagnostic accuracy of markers in patients with
PV >= 50 mL indicates a decrease in serum levels of PSA produced by prostate
cancer, which suggests growth inhibition of the cancer.
PMID- 29341454
TI - Socioeconomic deprivation and the burden of head and neck cancer-Regional
variations of incidence and mortality in Merseyside and Cheshire, North West,
England.
AB - OBJECTIVES: The aim of this longitudinal study was to examine the distribution of
head and neck cancer (HANC) disease burden across the region comparing it to
national trends. DESIGN: We undertook a retrospective study of routine data
combining it with indicators of deprivation and lifestyle at small geographical
areas within the 9 Local Authorities (LAs) of Merseyside and Cheshire Network
(MCCN) for head and neck cancers. Data from the North West of England and England
were used as comparator regions. SETTING: This research was undertaken by the
Cheshire and Merseyside Public Health Collaborative, UK. PARTICIPANTS: The
Merseyside and Cheshire region serves a population of 2.2 million. Routine data
allowed us to identify HANC patients diagnosed with cancers coded ICD C00-C14 and
C30-C32 within 3 cohorts 1998-2000, 2008-2010 and 2009-2011 for our analysis.
MAIN OUTCOME MEASURES: Directly age-standardised incidence rates and directly age
standardised mortality rates in the LAs and comparator regions were measured.
Lifestyle and deprivation indicators were plotted against them and measured by
Pearson's correlation coefficients. RESULTS: The incidence of head and neck
cancer has increased across the region from 1998-2000 to 2008-2010 with a peak
incidence for Liverpool males at 35/100 000 population. Certain Middle Super
Output Areas contribute disproportionately to the significant effect of incidence
and mortality within LAs. Income deprivation had the strongest correlation with
incidence (r = .59) and mortality (r = .53) of head and neck cancer. CONCLUSION:
Our study emphasises notable geographical variations within the region which need
to be addressed through public health measures.
PMID- 29341455
TI - Microsatellite markers for evaluating the diversity of the natural killer complex
and major histocompatibility complex genomic regions in domestic horses.
AB - Genotyping microsatellite markers represents a standard, relatively easy, and
inexpensive method of assessing genetic diversity of complex genomic regions in
various animal species, such as the major histocompatibility complex (MHC) and/or
natural killer cell receptor (NKR) genes. MHC-linked microsatellite markers have
been identified and some of them were used for characterizing MHC polymorphism in
various species, including horses. However, most of those were MHC class II
markers, while MHC class I and III sub-regions were less well covered. No tools
for studying genetic diversity of NKR complex genomic regions are available in
horses. Therefore, the aims of this work were to establish a panel of markers
suitable for analyzing genetic diversity of the natural killer complex (NKC), and
to develop additional microsatellite markers of the MHC class I and class III
genomic sub-regions in horses. Nine polymorphic microsatellite loci were newly
identified in the equine NKC. Along with two previously reported microsatellites
flanking this region, they constituted a panel of 11 loci allowing to
characterize genetic variation in this functionally important part of the horse
genome. Four newly described MHC class I/III-linked markers were added to 11
known microsatellites to establish a panel of 15 MHC markers with a better
coverage of the class I and class III sub-regions. Major characteristics of the
two panels produced on a group of 65 horses of 13 breeds and on five Przewalski's
horses showed that they do reflect genetic variation within the horse species.
PMID- 29341456
TI - Iron pill aspiration: Cytologic and histologic findings of a potential life
threatening airway injury. A Case report and literature review.
AB - Iron pill-induced injury of bronchial mucosa is a complication following
accidental aspiration of an iron tablet. Oral iron supplementation is a common
therapy, particularly among advanced-age patients, who are more prone to
aspiration. However, iron pill aspiration has been rarely reported in the
literature, usually under the format of short case reports, with only 32 cases
published in the literature. The cytologic features suspicious for this rare but
potentially lethal entity have been seldom described. We report a case of a
patient diagnosed with iron pill-induced bronchial injury, after oral ferrous
sulfate has been prescribed during a hospital admission for pneumonia. In the
bronchial washing specimen, a background of necrotic cell debris and acute
inflammation involving extracellular golden-brown fibrils positive for iron
stains was seen, along with the yeast forms, which, in this clinical context
could confirm the iron pill aspiration. Our aim is to highlight the cytology
features associated with iron pill aspiration bronchitis, and to review the
literature for the histologic, clinical, bronchoscopy, and treatment aspects.
PMID- 29341457
TI - Different effects of dexmedetomidine and midazolam on the expression of NR2B and
GABAA-alpha1 following peripheral nerve injury in rats.
AB - Neuropathic pain is a complex, chronic pain condition and the treatment is a
major clinical challenge. Recent studies have shown that two FDA approved drugs
dexmedetomidine (DEX) and midazolam (MZL), may be useful in treating neuropathic
pain, but the mechanism is not fully dementated. Here, we investigated the
effects and mechanisms of DEX and MZL treatment in the peripheral nerve injury
model. Intramuscular injection with DEX and MZL attenuated the development of
mechanical allodynia and thermal hyperalgesia in rats with chronic constriction
injury (CCI). Concurrently, the expression of NMDA receptor subunit 2B (NR2B),
GABA (A) receptor subunit alpha1 (GABAA-alpha1), and Sonic Hedgehog (SHH)
displayed different temporal patterns in the thalamus and the ipsilateral dorsal
horn of the spinal cord after CCI. Such that (1) NR2B expression was decreased on
day 1 and 14, whereas GABAA-alpha1 expression was increased on day 1 in the
thalamus, and NR2B expression was decreased on day 1, whereas GABAA-alpha1
expression was increased on day 1 and day 30 in the ipsilateral spinal cord
dorsal horn after DEX treatment. (2) NR2B expression was increased on day 1, then
decreased on day 14 and returned to baseline on day30, whereas GABAA-alpha1
expression was no significant changes on day 1, 14, 30 in the thalamus, and NR2B
expression was decreased on day 14 and 30, whereas GABAA-alpha1 expression was no
changes on day 1 and 14 but increased on day 30 after MZL treatment. Furthermore,
the mechanical allodynia was significantly attenuated after PUR administration.
Meanwhile the expression of NR2B was significantly decreased, and the expression
of GABAA-alpha1 was significantly increased, in the thalamus and in the
ipsilateral spinal cord dorsal horn when detected on postoperative day 1, 7, and
14. Our findings indicate that DEX and MZL have different mechanisms in CCI rats,
suggesting different strategies could be considered in managing neuropathic pain
in different individuals. (c) 2018 IUBMB Life, 70(2):143-152, 2018.
PMID- 29341458
TI - Procedural competency in emergency medicine training.
PMID- 29341460
TI - Intellectual disability and epilepsy due to the K/L-mediated Xq28 duplication:
Further evidence of a distinct, dosage-dependent phenotype.
AB - Copy number variants of the X-chromosome are a common cause of X-linked
intellectual disability in males. Duplication of the Xq28 band has been known for
over a decade to be the cause of the Lubs X-linked Mental Retardation Syndrome
(OMIM 300620) in males and this duplication has been narrowed to a critical
region containing only the genes MECP2 and IRAK1. In 2009, four families with a
distal duplication of Xq28 not including MECP2 and mediated by low-copy repeats
(LCRs) designated "K" and "L" were reported with intellectual disability and
epilepsy. Duplication of a second more distal region has been described as the
cause of the Int22h-1/Int22h-2 Mediated Xq28 Duplication Syndrome, characterized
by intellectual disability, psychiatric problems, and recurrent infections. We
report two additional families possessing the K/L-mediated Xq28 duplication with
affected males having intellectual disability and epilepsy similar to the
previously reported phenotype. To our knowledge, this is the second cohort of
individuals to be reported with this duplication and therefore supports K/L
mediated Xq28 duplications as a distinct syndrome.
PMID- 29341459
TI - Multicenter study of diagnostic procedures, genetic aberration analysis, and
first-line treatment of lung cancer in Jiangsu Province, China.
AB - BACKGROUND: Jiangsu Province, China, is highly developed economically and
culturally, and has a high prevalence of lung cancer. We aimed to evaluate the
diagnostic procedures, genetic aberration analysis status, and first-line
treatment models of lung cancer in Jiangsu Province. METHODS: Lung cancer
patients diagnosed in 2016 at 22 tertiary care hospitals were evaluated.
Demographic characteristics, tumor histology, staging, family history of lung
cancer, auxiliary examinations, genetic testing, and first-line treatment were
collected on discharge. Diagnostic and treatment data were analyzed by
descriptive statistics. RESULTS: A total of 928 patients were enrolled. Chest
computed tomography was the most frequently used diagnostic method; pathology
diagnosis was carried out by transbronchial lung biopsy and transthoracic needle
aspiration. Stage T1-2N0M0 small-cell lung cancer patients experienced surgical
resection, and others received cisplatin and etoposide chemotherapy. Stage I and
stage II non-small cell lung cancer patients experienced surgical resection;
stage III and stage IV patients received cisplatin and pemetrexed chemotherapy as
first-line treatment. Detection of epidermal growth factor receptor (EGFR)
mutations occurred in 29.9% of non-selective, 36.5% of locally advanced or
metastatic, and 42.1% of advanced non-squamous non-small cell lung cancer. The
overall EGFR-positive rates were 49.0%, 52.5%, and 53.9%. A total 72.0% of
patients with EGFR mutations were treated with tyrosine kinase inhibitors.
CONCLUSION: Chest computed tomography was the most commonly performed diagnostic
method for lung cancer. First-line treatment was primarily determined by disease
stages and EGFR mutation status, with few expectations.
PMID- 29341461
TI - Effect of immediate and prolonged GLP-1 receptor agonist administration on uric
acid and kidney clearance: Post-hoc analyses of four clinical trials.
AB - AIMS: To determine the effects of glucagon-like peptide (GLP)-1 receptor agonists
(RA) on uric acid (UA) levels and kidney UA clearance. MATERIAL AND METHODS: This
study involved post-hoc analyses of 4 controlled clinical trials, which assessed
actions of GLP-1RA administration on kidney physiology. The immediate effects of
GLP-1RA exenatide infusion vs placebo were determined in 9 healthy overweight men
(Study-A) and in 52 overweight T2DM patients (Study-B). The effects of 12 weeks
of long-acting GLP-1RA liraglutide vs placebo in 36 overweight T2DM patients
(Study-C) and of 8 weeks of short-acting GLP-1RA lixisenatide vs once-daily
titrated insulin glulisine in 35 overweight T2DM patients (Study-D) were also
examined. Plasma UA, fractional (inulin-corrected) and absolute urinary excretion
of UA (UEUA ) and sodium (UENa ), and urine pH were determined. RESULTS: Median
baseline plasma UA level was 5.39 to 6.33 mg/dL across all studies (17%-22% of
subjects were hyperuricaemic). In Study-A, exenatide infusion slightly increased
plasma UA (+0.07 +/- 0.02 mg/dL, P = .04), and raised absolute-UEUA (+1.58 +/-
0.65 mg/min/1.73 m2 , P = .02), but did not affect fractional UEUA compared to
placebo. Fractional UEUA and absolute UEUA correlated with increases in urine pH
(r:0.86, P = .003 and r:0.92, P < .001, respectively). Fractional UEUA correlated
with increased fractional UENa (r:0.76, P = .02). In Study-B, exenatide infusion
did not affect plasma UA, but increased fractional UEUA (+0.76 +/- 0.38%, P =
.049) and absolute UEUA (+0.75 +/- 0.27 mg/min/1.73 m2 , P = .007), compared to
placebo. In regression analyses, both parameters were explained by changes in
urine pH and, in part, by changes in UENa . In Study-C, liraglutide treatment did
not affect plasma UA, UEUA, UENa or urine pH, compared to placebo. In Study-D,
lixisenatide treatment increased UENa and urine pH from baseline, but did not
affect plasma UA or UEUA . CONCLUSION: Immediate exenatide infusion increases
UEUA in overweight healthy men and in T2DM patients, probably by inhibiting Na+
/H+ -exchanger type-3 in the renal proximal tubule. Prolonged treatment with a
long-acting or short-acting GLP-1RA does not affect plasma UA or UEUA in T2DM
patients with normal plasma UA levels and at relatively low cardiovascular risk.
Our results suggest that the cardio-renal benefits of GLP-1RA are not mediated
through changes in UA.
PMID- 29341462
TI - DNA Origami Scaffolds as Templates for Functional Tetrameric Kir3 K+ Channels.
AB - In native systems, scaffolding proteins play important roles in assembling
proteins into complexes to transduce signals. This concept is yet to be applied
to the assembly of functional transmembrane protein complexes in artificial
systems. To address this issue, DNA origami has the potential to serve as
scaffolds that arrange proteins at specific positions in complexes. Herein, we
report that Kir3 K+ channel proteins are assembled through zinc-finger protein
(ZFP)-adaptors at specific locations on DNA origami scaffolds. Specific binding
of the ZFP-fused Kir3 channels and ZFP-based adaptors on DNA origami were
confirmed by atomic force microscopy and gel electrophoresis. Furthermore, the
DNA origami with ZFP binding sites nearly tripled the K+ channel current activity
elicited by heterotetrameric Kir3 channels in HEK293T cells. Thus, our method
provides a useful template to control the oligomerization states of membrane
protein complexes in vitro and in living cells.
PMID- 29341463
TI - Synthetic phonics and decodable instructional reading texts: How far do these
support poor readers?
AB - This paper presents data from a quasi-experimental trial with paired
randomisation that emerged during the development of a reading scheme for
children in England. This trial was conducted with a group of 12 children, aged 5
6, and considered to be falling behind their peers in reading ability and a
matched control group. There were two intervention conditions (A: using mixed
teaching methods and a high percentage of non-phonically decodable vocabulary; P:
using mixed teaching methods and low percentage of non-decodable vocabulary);
allocation to these was randomised. Children were assessed at pre- and post-test
on standardised measures of receptive vocabulary, phoneme awareness, word
reading, and comprehension. Two class teachers in the same school each selected 6
children, who they considered to be poor readers, to participate (n = 12). A
control group (using synthetic phonics only and phonically decodable vocabulary)
was selected from the same 2 classes based on pre-test scores for word reading (n
= 16). Results from the study show positive benefits for poor readers from using
both additional teaching methods (such as analytic phonics, sight word
vocabulary, and oral vocabulary extension) in addition to synthetic phonics, and
also non-decodable vocabulary in instructional reading text.
PMID- 29341464
TI - Left sleeve lobectomy versus left pneumonectomy for the management of patients
with non-small cell lung cancer.
AB - BACKGROUND: The study was conducted to compare the outcomes of sleeve lobectomy
(SL) and pneumonectomy (PN) for management of the left lung in patients with non
small cell lung cancer (NSCLC). METHODS: One hundred and thirty-five patients who
underwent left SL (n = 87) or left PN (n = 48) for NSCLC from January 2006 to
December 2011 were enrolled in this retrospective study. Left SL was performed
when technically possible. The clinicopathological features and treatment
outcomes in both groups were compared. Survival was evaluated using the Kaplan
Meier method, and significant differences were calculated using the log-rank
test. Multivariate analysis was conducted using the Cox proportional hazards
model to analyze significant variables associated with the outcomes of left SL.
RESULTS: There were no significant differences in general clinicopathological
features (age, gender, lymph node metastasis, pathological stage, and
complications of bronchial fistula) between patients who underwent left SL and
left PN. The operation duration was markedly longer and the extent of bleeding
was greater for left SL than left PN; however patients who underwent left SL
achieved significantly longer overall survival than patients who underwent left
PN. The outcomes of left SL were only associated with pathological stage.
CONCLUSIONS: Our results indicate that left SL may offer superior survival than
left PN in selected patients. If anatomically feasible, left SL may be a
preferred alternative to left PN for NSCLC patients. Pathological stage is an
important factor to determine the outcome of SL.
PMID- 29341465
TI - P2Y12 deficiency in mouse impairs noradrenergic system in brain, and alters
anxiety-like neurobehavior and memory.
AB - Purinergic receptor P2Y12 (P2Y12 ), a G protein-coupled purinergic receptor, is
widely distributed in nervous system and involved in the progression of
neurological diseases such as multiple sclerosis and neuropathic pain. The
central noradrenergic system actively participates in a number of
neurophysiological processes. Nevertheless, whether there is any direct relevance
between P2Y12 and noradrenergic signal transduction remains unknown. In the
present study, we tested the hypothesis that lack of P2Y12 impaired noradrenergic
signal transduction in mouse brain. Our results showed that P2Y12 knockout (KO)
mice exhibited increased anxiety-like behavior in the open-field test (OFT) and
elevated plus maze test and displayed deficits in memory in the radial-arm maze
test (RAMT) and Morris water maze test (MWMT). They also exhibited reduced
locomotion in the OFT and MWMT. Moreover, loss of P2Y12 decreased the level of
noradrenaline and the expression of noradrenergic alpha receptors, subtypes
alpha2 (ARalpha2b) in mouse cerebellum and hippocampus. Meanwhile, it hampered
the protein kinase A (PKA)/cAMP response element-binding protein (CREB)/brain
derived neurotrophic factor (BDNF) signaling pathway in these brain regions.
Taken together, our results showed for the first time that P2Y12 KO altered the
anxiety, memory and locomotion of mice, which was closely associated with
abnormal state of noradrenergic system in the brain. The findings implicate that
P2Y12 plays an indispensable role in noradrenergic signal transduction; its
deficit is insufficient to limit anxiety responses or supports cognitive
performance and activity.
PMID- 29341466
TI - Effects of intravenous home dobutamine in palliative end-stage heart failure on
quality of life, heart failure hospitalization, and cost expenditure.
AB - AIMS: In patients with palliative end-stage heart failure, interventions that
could provide symptomatic relief and prevent hospital admissions are important.
Ambulatory continuous intravenous inotropes have been advocated by guidelines for
such a purpose. We sought to determine the effect of intravenous dobutamine on
symptomatic status, hospital stay, mortality, and cost expenditure. METHODS AND
RESULTS: All consecutive end-stage heart failure patients not amenable for
advanced therapies and discharged with continuous intravenous home dobutamine
from a single tertiary centre between April 2011 and January 2017 were
retrospectively analysed. Dobutamine (fixed dose) was infused through a single
lumen central venous catheter with a small pump that was refilled by a nurse on a
daily basis. Symptomatic status was longitudinally assessed as the change in New
York Heart Association class and patient global assessment scale. Antecedent and
incident heart failure hospitalizations were determined in a paired fashion, and
cost impact was assessed. A total of 21 patients (age 77 +/- 9 years) were
followed up for 869 +/- 647 days. At first follow-up (6 +/- 1 weeks) after the
initiation of dobutamine, patients had a significant improvement in New York
Heart Association class (-1.29 +/- 0.64; P < 0.001), global assessment scale
(<0.001), and N-terminal pro-brain natriuretic peptide (6247 vs. 2543 pg/mL; P =
0.033). Incident heart failure hospitalizations assessed at 3, 6, and 12 months
were significantly reduced (P < 0.001 for all) in comparison with antecedent
heart failure hospitalizations over the same time period. Cost expenditure was
significantly lower at 3 (P < 0.001), 6 (P = 0.005), and 12 months (P = 0.001)
after initiation of dobutamine. Mortality rate at 1 year was 48% with 9/12 (75%)
patients dying at home, most often from progressive pump failure. CONCLUSIONS:
Continuous intravenous home dobutamine in patients with palliative end-stage
heart failure is feasible and associated with improved symptomatic status, heart
failure hospitalizations, and health-care-related costs. Nevertheless, results
should be interpreted in the context of the small and retrospective design.
Larger studies are necessary to evaluate the effect of dobutamine in palliative
end-stage heart failure.
PMID- 29341467
TI - Optoacoustic sensing of hematocrit to improve the accuracy of hybrid fluorescence
ultrasound intravascular imaging.
AB - Hybrid intravascular fluorescence-ultrasound imaging is emerging for reading
anatomical and biological information in vivo. By operating through blood,
intravascular near-infrared fluorescence (NIRF) detection is affected by
hemoglobin attenuation. Improved quantification has been demonstrated with
methods that correct for the attenuation of the optical signal as it propagates
through blood. These methods assume an attenuation coefficient for blood and
measure the distance between detector and the vessel wall by observing the
intravascular ultrasound images. Assumptions behind the attenuation employed in
correction models may reduce the accuracy of these methods. Herein, we explore a
novel approach to dynamically estimate optical absorption by using optoacoustic
(photoacoustic) measurements. Adaptive correction is based on a trimodal
intravascular catheter that integrates fluorescence, ultrasound and optoacoustic
measurements. Using the novel catheter, we show how optoacoustic measurements can
determine variations of blood absorption, leading to accurate quantification of
the detected NIRF signals at different hematocrit values.
PMID- 29341468
TI - Downregulation of BarH-like homeobox 2 promotes cell proliferation, migration and
aerobic glycolysis through Wnt/beta-catenin signaling, and predicts a poor
prognosis in non-small cell lung carcinoma.
AB - BACKGROUND: Human BarH-like homeobox 2 (Barx2), a homeodomain factor of the Bar
family, plays a critical role in cell adhesion and cytoskeleton remodeling, and
has been reported in an increasing array of tumor types except non-small cell
lung carcinoma (NSCLC). The purpose of the current study was to characterize the
expression of Barx2 and assess the clinical significance of Barx2 in NSCLC.
METHODS: Quantitative real-time polymerase chain reaction, immunohistochemistry
and western blot analysis were used to examine mRNA and protein expression,
respectively. The relationships between Barx2 expression and clinicopathological
variables were analyzed. Cell Counting Kit-8 and plate colony formation assay
were used to detect cell proliferation. Transwell assay was used to examine cell
migration ability. Glucose uptake, lactate, adenosine triphosphate, and lactate
dehydrogenase assays were used to detect aerobic glycolysis. RESULTS: Barx2 is
downregulated in NSCLC tissues compared with para-carcinoma. Furthermore, Barx2
expression shows a negative correlation with advanced TNM stage and a high level
of Ki-67. Survival analysis reveals that Barx2 level is an independent prognostic
factor for NSCLC patients. The Barx2 (low) Ki-67 (high) group had the worst
prognosis. Furthermore, the data indicate that downregulation of Barx2 expression
promotes cell proliferation, migration, and aerobic glycolysis, including
increased lactate dehydrogenase activity, glucose utilization, lactate
production, and decreased intracellular adenosine triphospahte level.
Furthermore, Barx2 acts as a negative regulator of the canonical Wnt/beta-catenin
pathway. Reactivation of Wnt/beta-catenin pathway by LiCl can reverse the
inhibiting effect of Barx2. CONCLUSIONS: These findings reveal that Barx2 serving
as a tumor suppressor gene could decrease cell proliferation, migration, and
aerobic glycolysis through inhibiting the Wnt/beta-catenin signaling pathway, and
predicts a good prognosis in NSCLC.
PMID- 29341469
TI - Downregulation of CSN6 attenuates papillary thyroid carcinoma progression by
reducing Wnt/beta-catenin signaling and sensitizes cancer cells to FH535 therapy.
AB - The incidence of thyroid cancer has increased worldwide at a rate higher than
that of any other cancer. CSN6 is overexpressed in many types of cancers, and
such expression is linked to oncogenic activity. However, the detailed biological
functions of CSN6 in papillary thyroid cancer (PTC) have not been well
characterized. We investigated CSN6 expression in PTC specimens and cell lines.
We used short-hairpin RNA-mediated gene silencing to explore the biological
effects of CSN6 depletion in PTC cells. The combined effects of CSN6 silencing
and FH535 therapy were assessed in terms of cell viability. The mechanism by
which CSN6 regulated beta-catenin expression was also analyzed. CSN6 levels were
determined by real-time polymerase chain reaction (PCR) (mRNA), Western blotting,
and immunochemistry (protein). The CCK-8 and migration assays and orthotopic
xenograft transplantation were used to investigate the biological effects of
CSN6. We assessed the combined effects of CSN6 silencing and FH535 on cell
viability in vitro. We also analyzed the relationship between the CSN6 level and
clinical pathological status. CSN6 was overexpressed in human PTCs, and loss of
CSN6 attenuated tumor proliferation and migration both in vitro and in vivo. CSN6
stabilized beta-catenin and facilitated the epidermal-to-mesenchymal transition
(EMT) in PTC cells. CSN6 positively regulated beta-catenin expression in a beta
Trcp-dependent manner and triggered expression of several EMT-related genes
regulated by beta-catenin. CSN6 silencing sensitized PTC cells to FH535 therapy
via downregulation of the Wnt/beta-catenin signaling pathway. Finally, in PTC
patients, the level of CSN6 was significantly (inversely) correlated with tumor
size, the presence of multifocal lesions, and TNM stage. CSN6 overexpression in
PTC is a strong indicator of enhanced tumor aggressiveness. CSN6 promotes PTC
progression by inducing the EMT. CSN6 knockdown sensitizes PTC cells to FH535
therapy via downregulation of the Wnt/beta-catenin signaling pathway.
PMID- 29341470
TI - Cytological features of mixed adenoneuroendocrine carcinoma of the ampulla of
Vater: A case report with immunocytochemical analyses.
AB - Mixed adenoneuroendocrine carcinoma (MANEC) is defined as a tumor that has
morphologically recognizable both adenocarcinoma and neuroendocrine carcinoma
components comprising at least 30% of either components. MANEC occurring in the
ampulla of Vater is extremely rare, and only 16 cases have been reported in the
English language literature. In the present report, we describe the first case of
MANEC of the ampulla of Vater with immunocytochemical analyses. An 82-year-old
Japanese male was incidentally found to have a tumorous lesion in the ampulla of
Vater. Endoscopic ultrasound-fine needle aspiration (EUS-FNA) of the tumor was
performed. The Papanicolaou smear demonstrated the presence of different three
components. The most dominant component was cohesive clusters of small round
cells with round to oval nuclei with powdery chromatin and scant cytoplasm, which
corresponded to small cell carcinoma. The second component was an adenocarcinoma,
which was composed of irregularly overlapping clusters of tall columnar cells
with large round to oval nuclei containing conspicuous nucleoli. The third
component was an adenoma, which was comprised of flat cohesive clusters of
columnar cells without atypia. Immunocytochemical analyses demonstrated that
synaptophysin was expressed in the small round cells, and cdx-2 was expressed in
all three components. Accordingly, a cytodiagnosis of MANEC with adenoma
component was made. Preoperative diagnosis of ampullary MANEC is difficult.
However, this report clearly demonstrates three different components in the EUS
FNA cytological specimen. Therefore, we suggest that cytological examination is a
useful method for diagnosis of MANEC of the ampulla of Vater.
PMID- 29341472
TI - Characterization of the novel HLA-B*40:01:31 allele.
AB - The HLA-B*40:01:31 allele differs from B*40:01:01 by one nucleotide substitution
at position 216.
PMID- 29341471
TI - The impact of a dose of the angiotensin receptor blocker valsartan on post
myocardial infarction ventricular remodelling.
AB - AIMS: Although clinical guidelines advocate the use of the highest tolerated dose
of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers
after acute myocardial infarction (MI), the optimal dosing or the risk-benefit
profile of different doses have not been fully identified. METHODS AND RESULTS:
In this multicentre trial, 495 Korean patients with acute ST segment elevation MI
and subnormal left ventricular (LV) ejection fraction (<50%) were randomly
allocated (2:1) to receive maximal tolerated dose of valsartan (titrated up to
320 mg/day, n = 333) or low-dose valsartan (80 mg/day, n = 162) treatment. The
primary objective was to assess the changes in echocardiographic parameters of LV
remodelling from baseline to 12 months after discharge. After treatment, end
diastolic LV volume (LVEDV) decreased significantly in the low-dose group, but
the difference in LVEDV changes was insignificant between the maximal-tolerated
dose and low-dose groups. End-systolic LV volume decreased significantly in both
groups, to a similar degree between groups. LV ejection fraction rose
significantly in both study groups, to a similar degree. Changes in plasma levels
of neurohormones were also comparable between the two groups. Drug-related
adverse effects occurred more frequently in the maximal-tolerated-dose group than
in the low-dose group (7.96 vs. 0.69%, P < 0.001). CONCLUSIONS: In the present
study, treatment with the maximal tolerated dose of valsartan did not exhibit a
superior effect on post-MI LV remodelling compared with low-dose treatment and
was associated with a greater frequency of adverse effect in Korean patients.
Further study with a sufficient number of cases and statistical power is
warranted to verify the findings of the present study.
PMID- 29341473
TI - Somatic mosaic deletions involving SCN1A cause Dravet syndrome.
AB - Somatic mosaicism in single nucleotide variants of SCN1A is known to occur in a
subset of parents of children with Dravet syndrome (DS). Here, we report
recurrent somatic mosaic microdeletions involving SCN1A in children diagnosed
with DS. Through the evaluation of 237 affected individuals with DS who did not
show SCN1A or PCHD19 mutations in prior sequencing analyzes, we identified two
children with mosaic microdeletions covering the entire SCN1A region. The allele
frequency of the mosaic deletions estimated by multiplex ligation-dependent probe
amplification and array comparative genomic hybridization was 25-40%, which was
comparable to the mosaic ratio in lymphocytes and buccal mucosa cells observed by
fluorescence in situ hybridization analysis. The minimal prevalence of SCN1A
mosaic deletion is estimated to be 0.9% (95% confidence level: 0.11-3.11%) of DS
with negative for SCN1A and PCDH19 mutations. This study reinforces the
importance of somatic mosaicism caused by copy number variations in disease
causing genes, and provides an alternative spectrum of SCN1A mutations causative
of DS. Somatic deletions in SCN1A should be considered in cases with DS when
standard screenings for SCN1A mutations are apparently negative for mutations.
PMID- 29341474
TI - Effect of staining beverages on color and translucency of CAD/CAM composites.
AB - : This study investigated the color (DeltaE) and translucency changes (DeltaTP)
of CAD/CAM composites after exposure to staining solutions using both
spectrophotometer and shade-matching device. Direct (Filtek Z350XT [ZT]),
indirect (Shofu Ceramage [CE]) and CAD/CAM (Shofu HC Block [HC], Lava Ultimate
[LU], Vita Enamic [EN]) composite specimens measuring 12 * 14 * 1.5 mm were
fabricated, divided into five groups (n = 8), and immersed in cola, tea, coffee,
red wine, distilled water (control) at 37 degrees C for 7 days. Color parameters
were determined with both spectrophotometer and shade-taking device at baseline
and 1 week. Delta E (DeltaE) with white and black backgrounds, and Delta TP
(DeltaTP) were computed. Statistical testing was performed with ANOVA and Tukey
post hoc test (P < .05). Mean DeltaE (white) values ranged from 0.20 +/- 0.06 to
12.26 +/- 1.95 while mean DeltaE (black) varied from 0.22 +/- 0.11 to 14.21 +/-
2.37. Mean DeltaTP values ranged from 0.13 +/- 0.17 to -3.87 +/- 2.16. CAD/CAM
composites fared better in red wine than direct and indirect materials.
Clinically perceptible color changes (DeltaE > 3.3) were observed for almost all
materials when exposed to wine, coffee and tea. Direct, indirect, and CAD/CAM
composites are all susceptible to various degrees of discoloration and
translucency changes after exposure to staining beverages. Red wine caused the
most discoloration and translucency changes. Limitations of these materials must
be considered when placing an aesthetic restoration. CLINICAL SIGNIFICANCE:
Direct, indirect, and CAD/CAM composites are all susceptible to various degrees
of discoloration and translucency changes after exposure to staining beverages.
Red wine generally caused the most discoloration and translucency changes.
Although CAD/CAM composites were more color stable than direct and indirect
materials when exposed to red wine, color changes were still clinically
perceptible.
PMID- 29341475
TI - MicroRNA-664a-5p promotes neuronal differentiation of SH-SY5Y cells.
AB - MicroRNAs (miRNAs) belong to a class of small noncoding RNAs that play important
roles in the translational regulation of gene expression. A number of miRNAs are
known to act as key regulators of diverse processes such as neuronal
differentiation. In this study, we have attempted to identify novel miRNAs
related to neuronal differentiation via microarray analysis in the human neuronal
differentiation model neuroblastoma SH-SY5Y cells. We identified 15 up-regulated
and eight down-regulated miRNAs in SH-SY5Y cells treated with all-trans retinoic
acid to induce differentiation. We further showed that one of the up-regulated
miRNAs, miR-664a-5p, promoted neuronal differentiation of SH-SY5Y cells. These
findings enhance our understanding of the miRNAs involved in the process of
neurogenesis and, in particular, highlight an important role of miR-664a-5p in SH
SY5Y cell neuronal differentiation. Further studies will be required to confirm
the function of miR-664-5p in neuronal development and disease and to identify
its relevant target genes.
PMID- 29341476
TI - A rare male patient with classic Rett syndrome caused by MeCP2_e1 mutation.
AB - Rett syndrome (RTT) is a severe neurodevelopmental disorder typically affecting
females. It is mainly caused by loss-of-function mutations that affect the coding
sequence of exon 3 or 4 of methyl-CpG-binding protein 2 (MECP2). Severe neonatal
encephalopathy resulting in death before the age of 2 years is the most common
phenotype observed in males affected by a pathogenic MECP2 variant. Mutations in
MECP2 exon 1 affecting the MeCP2_e1 isoform are relatively rare causes of RTT in
females, and only one case of a male patient with MECP2-related severe neonatal
encephalopathy caused by a mutation in MECP2 exon 1 has been reported. This is
the first reported case of a male with classic RTT caused by a 5-bp duplication
in the open-reading frame of MECP2 exon 1 (NM_001110792.1:c.23_27dup) that
introduced a premature stop codon [p.(Ser10Argfs*36)] in the MeCP2_e1 isoform,
which has been reported in one female patient with classic RTT. Therefore, both
males and females displaying at least some type of MeCP2_e1 mutation may exhibit
the classic RTT phenotype.
PMID- 29341477
TI - Evidence-based adequacy criteria for instrumented urine cytology using cytospin
preparations.
AB - Cytospin preparations of instrumented urine cytology specimens with less than 10
urothelial cells or more than 50 urothelial cells/10 hpfs are both associated
with significantly increased false negative rates compared to cases with 10-49
urothelial cells/10 hpfs.
PMID- 29341478
TI - Translational systems pharmacology-based predictive assessment of drug-induced
cardiomyopathy.
AB - Drug-induced cardiomyopathy contributes to drug attrition. We compared two
pipelines of predictive modeling: (1) applying elastic net (EN) to differentially
expressed genes (DEGs) of drugs; (2) applying integer linear programming (ILP) to
construct each drug's signaling pathway starting from its targets to downstream
proteins, to transcription factors, and to its DEGs in human cardiomyocytes, and
then subjecting the genes/proteins in the drugs' signaling networks to EN
regression. We classified 31 drugs with availability of DEGs into 13 toxic and 18
nontoxic drugs based on a clinical cardiomyopathy incidence cutoff of 0.1%. The
ILP-augmented modeling increased prediction accuracy from 79% to 88%
(sensitivity: 88%; specificity: 89%) under leave-one-out cross validation. The
ILP-constructed signaling networks of drugs were better predictors than DEGs. Per
literature, the microRNAs that reportedly regulate expression of our six top
predictors are of diagnostic value for natural heart failure or doxorubicin
induced cardiomyopathy. This translational predictive modeling might uncover
potential biomarkers.
PMID- 29341479
TI - Nuclear division cycle 80 promotes malignant progression and predicts clinical
outcome in colorectal cancer.
AB - Colorectal cancer (CRC) is a common human malignancy worldwide and increasing
studies have attributed its malignant progression to abnormal molecular changes
in cancer cells. Nuclear division cycle 80 (NDC80) is a newly discovered
oncoprotein that regulates cell proliferation and cycle in numerous malignancies.
However, its clinical significance and biological role in CRC remain unclear.
Therefore, in this study, we firstly analyze its expression in a retrospective
cohort enrolling 224 CRC patients and find its overexpression is significantly
correlated with advanced tumor stage and poor prognosis in CRC patients. In
addition, our result reveals it is an independent adverse prognostic factor
affecting CRC-specific and disease-free survival. The subgroup analysis indicates
NDC80 expression can stratify the clinical outcome in stage II and III patients,
but fails in stage I and IV patients. In cellular assays, we find knockdown of
NDC80 dramatically inhibits the proliferative ability, apoptosis resistance, cell
cycle progression, and clone formation of CRC cells in vitro. Using xenograft
model, we further prove knockdown of NDC80 also inhibits the tumorigenic ability
of CRC cells in vivo. Finally, the microarray analysis is utilized to
preliminarily clarify the oncogenic molecular mechanisms regulated by NDC80 and
the results suggest it may promote CRC progression partly by downregulating tumor
suppressors such as dual specificity phosphatase 5 and Forkhead box O1. Taken
together, our study provides novel evidences to support that NDC80 is not only a
promising clinical biomarker but also a potential therapeutical target for CRC
precise medicine.
PMID- 29341481
TI - Sleep medication, sleep duration and healthcare utilization among older adults.
PMID- 29341482
TI - Association between polypharmacy and clinical ward pharmacy services in hospitals
in Tokyo.
PMID- 29341480
TI - Cutis laxa and excessive bone growth due to de novo mutations in PTDSS1.
AB - The cutis laxa syndromes are multisystem disorders that share loose redundant
inelastic and wrinkled skin as a common hallmark clinical feature. The underlying
molecular defects are heterogeneous and 13 different genes have been involved
until now, all of them being implicated in elastic fiber assembly. We provide
here molecular and clinical characterization of three unrelated patients with a
very rare phenotype associating cutis laxa, facial dysmorphism, severe growth
retardation, hyperostotic skeletal dysplasia, and intellectual disability. This
disorder called Lenz-Majewski syndrome (LMS) is associated with gain of function
mutations in PTDSS1, encoding an enzyme involved in phospholipid biosynthesis.
This report illustrates that LMS is an unequivocal cutis laxa syndrome and
expands the clinical and molecular spectrum of this group of disorders. In the
neonatal period, brachydactyly and facial dysmorphism are two early distinctive
signs, later followed by intellectual disability and hyperostotic skeletal
dysplasia with severe dwarfism allowing differentiation of this condition from
other cutis laxa phenotypes. Further studies are needed to understand the link
between PTDSS1 and extra cellular matrix assembly.
PMID- 29341483
TI - Use of a human-type communication robot to evaluate the categorized communicative
ability of older adults with dementia.
PMID- 29341484
TI - Nasal ventilation is an important factor in evaluating the diagnostic value of
nasal nitric oxide in allergic rhinitis.
AB - BACKGROUND: The role of nasal nitric oxide (NO) in the diagnosis of allergic
rhinitis (AR) is controversial. The aim of this study was to identify factors
that may affect levels of nasal NO in AR patients and evaluate the role of nasal
NO in the diagnosis of AR. METHODS: Seventy-five AR patients and 31 healthy
controls were enrolled in this study. AR symptom scores were assessed using the
visual analog scale. Eosinophil cationic protein (ECP) was detected by enzyme
linked immunoassay, nasal NO was measured using a chemiluminescence analyzer, and
nasal airway resistance (NAR) was assessed by active anterior rhinomanometry.
RESULTS: Nasal obstruction score, ECP, and NAR were found to be independently
associated with nasal NO. Nasal NO level in patients with nasal obstruction score
<7 (mild-to-moderate obstruction) was significantly increased compared with
healthy subjects (282.1 +/- 122.6 vs 150.7 +/- 48.4 ppb; p < 0.001), and
significantly decreased in patients with nasal obstruction score >=7 (severe
obstruction) (97.2 +/- 52.2 vs 150.7 +/- 48.4 ppb; p < 0.001). Nasal NO and ECP
in secretion were positively correlated in patients with mild-to-moderate nasal
obstruction (r = 0.678), but not in patients with severe nasal obstruction (r =
0.077). In patients with NAR <0.65 Pa/cm3 /s, the correlation coefficient was
highest between NO and ECP (r = 0.685). The areas under the receiver operating
characteristic curve for nasal NO level were 0.878 and 0.939 in patients with
nasal obstruction scores <7 and NAR <0.65 Pa/cm3 /s, respectively. CONCLUSION:
Nasal patency affects nasal NO level significantly, and may reflect the severity
of nasal inflammation in AR patients with mild-to-moderate nasal obstruction, but
not in patients with severe nasal obstruction.
PMID- 29341485
TI - Development of a chemiluminescence immunoassay using recombinant non-structural
epitope-based proteins to accurately differentiate foot-and-mouth disease virus
infected and vaccinated bovines.
AB - The contamination of inactivated vaccine with non-structural proteins (NSPs)
leads to a high false-positive rate, which is a substantial barrier to accurately
differentiate foot-and-mouth disease virus (FMDV)-infected animals from
vaccinated animals. To address this problem, a new chemiluminescence immunoassay
(CLIA) method was developed to detect antibodies targeting the two recombinant
epitope-based proteins located in 3A and 3B. The 3Aepitp-3Bepitp CLIA exhibited a
diagnostic sensitivity of 94.0% and a diagnostic specificity of 97.5% for the
detection of serum samples (naive bovines, n = 52, vaccinated bovines, n = 422,
infected bovines, n = 116) from animals with known status. The CLIA method also
had a concordance rate of 88.1% with the PrioCHECK FMDV NSP ELISA based on the
detection of 270 serum samples from the field. Importantly, the 3Aepitp-3Bepitp
CLIA produced no false-positives when used to detect FMDV in samples from bovines
that had been vaccinated up to five times, and it was demonstrated a low false
positive rate when the bovines had been vaccinated up to ten (2.15%) and fifteen
times (5.93%). Therefore, the 3Aepitp-3Bepitp CLIA detects FMDV in samples from
frequently vaccinated bovines with high accuracy and represents an alternative
method to differentiate FMDV-infected and vaccinated bovines.
PMID- 29341486
TI - Rheumatoid arthritis and periodontal disease: What are the similarities and
differences?
AB - Rheumatoid arthritis (RA) and periodontal disease (PD) are chronic inflammatory
diseases that share similar osteoclasia, human leukocyte antigen-DR4 allelic
genes and immunological profile, and characteristic cytokines. Smoking can
contribute to more severe RA and PD; secretion of pro-inflammatory mediators
destroys the soft synovial membrane and periodontium, respectively. Anti
citrullinated protein antibodies and anti-alpha-enolase antibody are
characteristic of these two diseases. Some studies suggest that PD may be
associated with RA. Anti-Porphyromonas gingivalis (P. gingivalis) antibody, but
no P. gingivalis bacterium can be detected in RA patients' joint fluid. Anti-P.
gingivalis antibody has been seen as a biomarker of RA. Both diseases share some
nosogenesis and common pathological pathways. However, there are differing views
on the connection between the two diseases. Interferon-inducible-16 (IFI16) is a
genic marker of RA; moreover, the association between IFI16 and PD is rare. Some
studies suggest PD is related to periodontal parameters and patient's
pathological status rather than RA. Disease frequency in men and women differ
between these two diseases. The expression of interleukin-17 (IL-17) receptor
only associates with different genders in PD (PD of different sexes have
different IL-17 expressions). Periodontal local treatment only affects clinical
periodontal status, and it does not alter circulating levels of IL-6, tumor
necrosis factor-alpha or C-reactive protein which are associated with RA. This
review examines the similarities and differences between these two diseases and
explores possible interactions. Importantly, we will discuss whether PD is a
feature of RA and whether this knowledge provides helpful information in future
treatment of both diseases.
PMID- 29341487
TI - Identification of stress-related microRNA biomarkers in type 2 diabetes mellitus:
A systematic review and meta-analysis.
AB - BACKGROUND: Many studies have investigated microRNAs (miRNAs) in the detection of
type 2 diabetes mellitus (T2DM). Herein, the dysregulated direction of stress
related miRNAs used as biomarkers of T2DM are summarized and analyzed. METHODS:
PubMed, EMBASE, ISI Web of Science, and three Chinese databases were searched for
case-control miRNA profiling studies about T2DM. A meta-analysis under a random
effect was performed. Subgroup analysis was conducted based on different tissues
and species. Sensitivity analysis was conducted to confirm the robustness among
studies. The effect size was pooled using ln odds ratios (ORs), 95% confidence
intervals (95% CIs), and P-values. RESULTS: The present meta-analysis included 39
case-control studies with a total of 494 miRNAs. Only 33 miRNAs were reported in
three or more studies and, of these, 18 were inconsistent in their direction of
dysregulation. Two significantly dysregulated miRNAs (let-7 g and miR-155) were
identified in the meta-analysis. Four miRNAs (miR-142-3p, miR-155, miR-21, and
miR-34c-5p) were dysregulated in patients with T2DM, whereas five miRNAs (miR
146a, miR-199a-3p, miR-200b, miR-29b and miR-30e) were dysregulated in animal
models of diabetes. In addition, two dysregulated miRNAs (miR-146a and miR-21)
were highly cornea specific and heart specific. In sensitivity analysis, only miR
155 was still significantly dysregulated after removing studies with small sample
sizes. CONCLUSIONS: The present meta-analysis revealed that 16 stress-related
miRNAs were significantly dysregulated in T2DM. MiR-148b, miR-223, miR-130a, miR
19a, miR-26b and miR-27b were selected as potential circulating biomarkers of
T2DM. In addition, miR-146a and miR-21 were identified as potential tissue
biomarkers of T2DM.
PMID- 29341488
TI - Gene-gene interaction between MSX1 and TP63 in Asian case-parent trios with
nonsyndromic cleft lip with or without cleft palate.
AB - BACKGROUND: Small ubiquitin-like modification, also known as sumoylation, is a
crucial post-translational regulatory mechanisms involved in development of the
lip and palate. Recent studies reported two sumoylation target genes, MSX1 and
TP63, to have achieved genome-wide level significance in tests of association
with nonsyndromic clefts. Here, we performed a candidate gene analysis
considering gene-gene and gene-environment interaction for SUMO1, MSX1, and TP63
to further explore the etiology of nonsyndromic cleft lip with or without cleft
palate (NSCL/P). METHODS: A total of 130 single-nucleotide polymorphisms (SNPs)
in or near SUMO1, MSX1, and TP63 was analyzed among 1,038 Asian NSCL/P trios
ascertained through an international consortium. Conditional logistic regression
models were used to explore gene-gene (G * G) and gene-environment (G * E)
interaction involving maternal environmental tobacco smoke and multivitamin
supplementation. Bonferroni correction was used for G * E analysis and
permutation tests were used for G * G analysis. RESULTS: While transmission
disequilibrium tests and gene-environment interaction analysis showed no
significant results, we did find signals of gene-gene interaction between SNPs
near MSX1 and TP63. Three pairwise interactions yielded significant p values in
permutation tests (rs884690 and rs9290890 with p = 9.34 * 10-5 and empirical p =
1.00 * 10-4 , rs1022136 and rs4687098 with p = 2.41 * 10-4 and empirical p = 2.95
* 10-4 , rs6819546 and rs9681004 with p = 5.15 * 10-4 and empirical p = 3.02 * 10
4 ). CONCLUSION: Gene-gene interaction between MSX1 and TP63 may influence the
risk of NSCL/P in Asian populations. Our study provided additional understanding
of the genetic etiology of NSCL/P and underlined the importance of considering
gene-gene interaction in the etiology of this common craniofacial malformation.
PMID- 29341489
TI - Palladium-Catalyzed Atom-Transfer Radical Cyclization at Remote Unactivated C(sp3
)-H Sites: Hydrogen-Atom Transfer of Hybrid Vinyl Palladium Radical
Intermediates.
AB - A novel mild, visible-light-induced palladium-catalyzed hydrogen atom
translocation/atom-transfer radical cyclization (HAT/ATRC) cascade has been
developed. This protocol involves a 1,5-HAT process of previously unknown hybrid
vinyl palladium radical intermediates, thus leading to iodomethyl carbo- and
heterocyclic structures.
PMID- 29341490
TI - Containing influenza outbreaks with antiviral use in long-term care facilities in
Taiwan, 2008-2014.
AB - BACKGROUNDS: Influenza can spread rapidly in long-term care facilities (LTCFs),
and residents are usually at higher risk for influenza infections. OBJECTIVE: Our
study aimed to evaluate the effectiveness of antiviral interventions on outbreak
control. METHODS: Taiwan Centers for Disease Control used a syndromic
surveillance system to monitor outbreaks in LTCFs. Local public health
authorities verified those outbreaks and logged reports to the Epidemic
Investigation Report Files Management System (EIRFMS). We conducted a
retrospective cohort study by reviewing EIRFMS reports of influenza outbreaks in
LTCFs during 2008-2014. An influenza outbreak was defined as 3 or more cases of
influenza-like illness occurring within a 48-hours period with >=1 case of real
time RT-PCR-confirmed influenza in the same LTCF. Antiviral interventions
included providing antiviral treatment for patients and antiviral prophylaxis for
contacts during outbreaks. RESULTS: Of 102 influenza outbreaks, median days from
onset of the first patient to outbreak notification was 4 (range 0-22). Median
attack rate was 24% (range 2.2%-100%). Median influenza vaccination coverage
among residents was 81% (range 0%-100%); 43% occurred during the summer months.
Even though antiviral treatment was provided in 87% of the outbreaks, antiviral
prophylaxis was implemented in only 40%. Starting antiviral treatment within 2
days of outbreak onset was associated with keeping attack rates at <25% (OR 0.29,
95% CI: 0.12-0.71). CONCLUSIONS: Early initiation of antiviral treatment may
reduce the magnitude of influenza outbreaks. Clinicians should identify patients
with influenza and start antiviral use early to prevent large outbreaks in LTCFs.
PMID- 29341492
TI - Winner of the society for biomaterials student award in the Ph.D. category for
the annual meeting of the society for biomaterials, april 11-14, 2018, Atlanta,
GA: Development of a bimodal, in situ crosslinking method to achieve multifactor
release from electrospun gelatin.
AB - To better mimic native tissue microenvironments, current efforts have moved
beyond single growth factor delivery to more complex multiple growth factor
delivery with distinct release profiles. Electrospun gelatin, a widely
investigated drug delivery vehicle, requires postprocessing crosslinking
techniques that generate a mesh with uniform crosslinking density, limiting the
ability to deliver multiple factors at different rates. Herein, we describe a
method to independently control release of multiple factors from a single
electrospun gelatin mesh. Two in situ crosslinking modalities, photocrosslinking
of methacyrlated gelatin and reactive crosslinking of gelatin with a
diisocyanate, are coelectrospun to generate distinct fiber populations with
different crosslinking chemistry and density in a single mesh. The
photocrosslinked gelatin-methacrylate resulted in a relatively rapid release of a
model protein (48 +/- 12% at day 1, 96 +/- 3% at day 10) due to diffusion of
embedded protein from the crosslinked fibers. The reactive crosslinking system
displayed a more sustained release (7 +/- 5% at day 1, 33 +/- 2% at day 10) that
was attributed to the conjugation of protein to gelatin with the diisocyanate,
requiring degradation of gelatin prior to diffusion out of the fibers. Both
modalities displayed tunable release profiles. Subsequent release studies of a
cospun mesh with two different crosslinked fiber populations confirmed that the
cospun mesh displayed multifactor release with independent release profiles.
Overall, this bimodal, in situ crosslinking approach enables the delivery of
multiple factors with distinct release kinetics from a single mesh and is
expected to have broad utility in tissue engineering. (c) 2018 Wiley Periodicals,
Inc. J Biomed Mater Res Part A: 106A: 1155-1164, 2018.
PMID- 29341491
TI - Clinical outcomes of carbon ion radiotherapy with concurrent chemotherapy for
locally advanced uterine cervical adenocarcinoma in a phase 1/2 clinical trial
(Protocol 1001).
AB - We conducted a phase 1/2 study to evaluate the efficacy and safety of carbon ion
radiotherapy (C-ion RT) with concurrent chemotherapy for locally advanced uterine
cervical adenocarcinoma. Thirty-three patients were enrolled between April 2010
and March 2014. Treatment consisted of C-ion RT with concurrent weekly cisplatin
at a dose of 40 mg/m2 . In the phase 1 component, the total dose was escalated
from 68.0 Gy (relative biological effectiveness [RBE]) to 74.4 Gy (RBE) to
determine the maximum tolerated dose of C-ion RT. In the phase 2 component, the
efficacy and safety of C-ion RT with concurrent chemotherapy were evaluated using
the dose determined in the phase 1 component. The median follow-up duration was
30 months. Two patients did not receive chemotherapy because of anemia or
leukocytopenia immediately prior to commencing treatment; 31 patients were
analyzed. None of the patients developed dose-limiting toxicities. The
recommended dose (RD) was determined to be 74.4 Gy (RBE). In the phase 2
component, two patients developed Grade 3-4 toxicities in the gastrointestinal
tract, due to repeated laser coagulation or peritonitis caused by appendicitis.
In the patients treated with the RD, the 2-year local control, progression-free
survival, and overall survival rates were 71%, 56%, and 88%, respectively. C-ion
RT with concurrent weekly cisplatin was well tolerated in patients with locally
advanced uterine cervical adenocarcinoma. Our findings support further
investigations into the efficacy of this strategy.
PMID- 29341493
TI - Modeling the Downstream Processing of Monoclonal Antibodies Reveals Cost
Advantages for Continuous Methods for a Broad Range of Manufacturing Scales.
AB - The biopharmaceutical industry is evolving in response to changing market
conditions, including increasing competition and growing pressures to reduce
costs. Single-use (SU) technologies and continuous bioprocessing have attracted
attention as potential facilitators of cost-optimized manufacturing for
monoclonal antibodies. While disposable bioprocessing has been adopted at many
scales of manufacturing, continuous bioprocessing has yet to reach the same level
of implementation. In this study, the cost of goods of Pall Life Science's
integrated, continuous bioprocessing (ICB) platform is modeled, along with that
of purification processes in stainless-steel and SU batch formats. All three
models include costs associated with downstream processing only. Evaluation of
the models across a broad range of clinical and commercial scenarios reveal that
the cost savings gained by switching from stainless-steel to SU batch processing
are often amplified by continuous operation. The continuous platform exhibits the
lowest cost of goods across 78% of all scenarios modeled here, with the SU batch
process having the lowest costs in the rest of the cases. The relative savings
demonstrated by the continuous process are greatest at the highest feed titers
and volumes. These findings indicate that existing and imminent continuous
technologies and equipment can become key enablers for more cost effective
manufacturing of biopharmaceuticals.
PMID- 29341494
TI - The importance of biomarkers of fetal exposure to alcohol and psychotropic drugs
in early diagnosis: A case report.
PMID- 29341495
TI - Validation of a fully automated solid-phase extraction and ultra-high-performance
liquid chromatography-tandem mass spectrometry method for quantification of 30
pharmaceuticals and metabolites in post-mortem blood and brain samples.
AB - In this study, we present the validation of an analytical method capable of
quantifying 30 commonly encountered pharmaceuticals and metabolites in whole
blood and brain tissue from forensic cases. Solid-phase extraction was performed
by a fully automated robotic system, thereby minimising manual labour and human
error while increasing sample throughput, robustness, and traceability. The
method was validated in blood in terms of selectivity, linear range, matrix
effect, extraction recovery, process efficiency, carry-over, stability,
precision, and accuracy. Deuterated analogues of each analyte were used as
internal standards, which corrected adequately for any inter-individual
variability in matrix effects on analyte accuracy and precision. The lower limit
of quantification (LLOQ) spanned from 0.0008 to 0.010 mg/kg, depending on the
analyte, while the upper LOQ ranged between 0.40 and 2.0 mg/kg. Thus, the linear
range covered both therapeutic and toxic levels. The method showed acceptable
accuracy and precision, with accuracies ranging from 80 to 118% and precision
below 19% for the majority of the analytes. Linear range, matrix effect,
extraction recovery, process efficiency, precision, and accuracy were also tested
in brain homogenate and the results agreed with those from blood. An additional
finding was that the analyte concentrations in brain samples could be quantified
by calibration curves obtained from spiked blood samples with acceptable
precision and accuracy when using deuterated analogues of each analyte as
internal standards. This method has been successfully implemented as a routine
analysis procedure for quantification of pharmaceuticals in both blood and brain
tissue since 2015.
PMID- 29341496
TI - Association of genetic variants in the interleukin-18 gene promoter with risk of
hepatocellular carcinoma and metastasis in patients with hepatitis C virus
infection.
AB - Hepatocellular carcinoma (HCC) is a primary malignancy of the liver,
characterized by high vascularization and rapid tumor progression. The current
case-control study aimed to analyze the influence of -607C/A and -137G/C
polymorphisms in the interleukin-18 (IL-18) promoter on the risk of HCC
occurrence and metastasis in Egyptian patients infected with hepatitis C virus
(HCV). Both genetic variations were genotyped in 279 subjects including HCV
patients with and without HCC and unrelated healthy subjects, using the allele
specific polymerase chain reaction (AS-PCR) method. The relationship between
clinico-laboratory parameters including serum level of alpha-fetoprotein (AFP)
and these polymorphisms was evaluated in HCC patients. The IL-18-607A allele and
AA genotype were significantly related to a higher risk of developing HCC when
comparing patients with HCC and controls, and were significantly related to a
higher risk of metastasis when comparing metastatic and nonmetastatic groups in
the Egyptian patients. In contrast, the IL18-137C allele and GC genotype were
significantly related to a lower risk of developing HCC when comparing patients
with HCC and controls, and HCV patients with and without HCC. A significant
association was found between multinodular HCC and IL-18-607AA genotype, while,
uninodular HCC was significantly associated with IL-18-137GG genotype. In
addition, IL18-607AA and -137GG genotypes showed significant association with
higher level of serum AFP. The detection of polymorphisms in the IL-18 promoter,
in a combination with an evaluation of level of serum AFP, could be used as a
molecular biomarker in the early diagnosis of HCC, which would aid the early
management of the disease, thus decreasing the rate of mortality of this disease.
(c) 2018 IUBMB Life, 70(2):165-174, 2018.
PMID- 29341497
TI - Defining behavioral components of social functioning in adults with autism
spectrum disorder as targets for treatment.
AB - : There is increasing recognition that adults with autism spectrum disorder (ASD)
would benefit from treatment to improve social functioning, a key factor in
adults' overall quality of life. However, the various behavioral components of
social functioning (i.e., categories of behaviors underlying social functioning),
including social motivation, social anxiety, social cognition, and social skills,
have not all been assessed together in any sample of adults with ASD, making it
difficult to know the relative levels of impairment in these various categories,
the relationships among these categories, or promising targets for treatments. We
hypothesized there would be significant correlations among measures within the
same category, but fewer correlations of measures between categories, indicating
the heterogeneity of impairments in adults with ASD. Twenty-nine adults with ASD
without co-occurring intellectual disability completed multiple assessments
measuring social motivation, social anxiety, social cognition, and social skills,
as well as measures of overall ASD symptom levels and community functioning.
Results revealed significant positive correlations among measures within most
categories; positive correlations between measures of social motivation and all
other categories, except for social cognition; as well as positive cross-domain
correlations between measures of anxiety and ASD phenotype; measures of social
skills and community functioning; and measures of social skills and ASD
phenotype. Further studies are warranted to determine causal relationships among
these behavioral categories, across developmental stages. However, the lack of
correlations between many categories suggests the potential importance of
multidimensional treatments that target the particular components of social
functioning most in need of improvement in individuals. Autism Res 2018, 11: 488
502. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
LAY SUMMARY: The goal of this study was to measure behaviors that contribute to
social functioning difficulties in adults with ASD, with the ultimate goal of
guiding treatment development. We found that motivation to interact with others
was significantly related to social anxiety and social skill. Our results suggest
that motivation may be important to target in treatment, and that treatments
should be tailored to the areas most in need of improvement in each individual.
PMID- 29341498
TI - Review article: Sepsis in the emergency department - Part 2: Investigations and
monitoring.
AB - Sepsis is characterised by organ dysfunction resulting from infection, with no
reliable single objective test and current diagnosis based on clinical features
and results of investigations. In the ED, investigations may be conducted to
diagnose infection as the cause of the presenting illness, identify the source,
distinguish sepsis from uncomplicated infection (i.e. without organ dysfunction)
and/ or risk stratification. Appropriate sample collection for microbiological
testing remains key for subsequent confirmation of diagnosis and rationalisation
of antimicrobials. Routine laboratory investigations such as creatinine,
bilirubin, platelet count and lactate are now critical elements in the diagnosis
of sepsis and septic shock. With no biomarker sufficiently validated to rule out
bacterial infection in the ED, there remains substantial interest in biomarkers
representing various pathogenic pathways. New technologies for screening multiple
genes and proteins are identifying unique network 'signatures' of clinical
interest. Other future directions include rapid detection of bacterial DNA in
blood, genes for antibiotic resistance and EMR-based computational biomarkers
that collate multiple information sources. Reliable, cost-effective tests,
validated in the ED to promptly and accurately identify sepsis, and to guide
initial antibiotic choices, are important goals of current research efforts.
PMID- 29341499
TI - Recommendations on diagnostic tools for Batrachochytrium salamandrivorans.
AB - Batrachochytrium salamandrivorans (Bsal) poses a major threat to amphibian, and
more specifically caudata, diversity. Bsal is currently spreading through Europe,
and mitigation measures aimed at stopping its spread and preventing its
introduction into naive environments are urgently needed. Screening for presence
of Bsal and diagnosis of Bsal-induced disease in amphibians are essential core
components of effective mitigation plans. Therefore, the aim of this study was to
present an overview of all Bsal diagnostic tools together with their limitations
and to suggest guidelines to allow uniform interpretation. Here, we investigate
the use of different diagnostic tools in post-mortem detection of Bsal and
whether competition between Bd and Bsal occurs in the species-specific Bd and
Bsal duplex real-time PCR. We also investigate the diagnostic sensitivity,
diagnostic specificity and reproducibility of the Bsal real-time PCR and show the
use of immunohistochemistry in diagnosis of Bsal-induced chytridiomycosis in
amphibian samples stored in formaldehyde. Additionally, we have drawn up
guidelines for the use and interpretation of the different diagnostic tools for
Bsal currently available, to facilitate standardization of execution and
interpretation.
PMID- 29341500
TI - Investigation of the free heavy chain homodimers of a monoclonal antibody.
AB - Monoclonal antibodies (mAbs) are composed of two heavy chain (HC) and two light
chain (LC) polypeptides. The proper folding and assembly of HC and LC is critical
for antibody production. Current dogma indicates that the free HCs are retained
in the endoplasmic reticulum (ER) unless assembled with LCs into antibodies,
while the LCs on the other hand can be secreted as free monomer or dimer
molecules. In this study, high levels of extracellular HC homodimers (7%-45%)
were observed in the cell culture media during cell line development for mAb1.
Excellent correlation (R2 > 0.9) between the level of free HC homodimers and the
percentage of high molecular weight species indicates that the free HC homodimers
might be causative of unwanted aggregation. Due to the different surface charge
of HC homodimer and fully assembled antibodies, the unwanted extracellular HC
homodimers were successfully removed by downstream processing, through a cation
exchange chromatography step. Reduced capillary electrophoresis-sodium dodecyl
sulfate (rCE-SDS) analysis of the cell culture media from different MTX-amplified
pools indicated that insufficient expression of LC is one potential root cause
for the high level of free HC homodimers. The level of free HC homodimers
decreased significantly (3%-25%) after retransfecting the MTX amplified pools
with additional LC gene. (c) 2018 American Institute of Chemical Engineers
Biotechnol. Prog., 34:738-745, 2018.
PMID- 29341501
TI - Tadalafil Improves Symptoms, Erectile Function and Quality of Life in Patients
with Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia (KYU
PRO Study).
AB - OBJECTIVES: Effect of tadalafil on lower urinary tract symptoms (LUTS), erectile
function and quality of life (QoL) were prospectively evaluated in patients with
benign prostatic hyperplasia (BPH) at multicenter. METHODS: Eligible men were
>=40 years who had no treatment with alpha-blocker for BPH, with total
International Prostate Symptom Score (IPSS) >=8, IPSS-QOL >=2 and prostate volume
>=20 mL. Data were collected on age, body mass index (BMI), and prostate specific
antigen (PSA). Patients were asked to complete a self-reported questionnaire
regarding the IPSS, Overactive Bladder Symptom Score (OABSS), International Index
of Erectile Function 5 (IIEF5), and Medical Outcome Study 8-Item Short-Form
Health Survey (SF-8). These measures were assessed at baseline, 4-, 8-, 12-week
of tadalafil treatment. In addition, uroflowmetry was also performed at baseline,
and 12-week end point visit. RESULTS: Thirty five patients with mean age 67.3
years, mean BMI 23.6 kg/m2 , mean prostate volume 36 mL, and mean PSA 3.4 ng/mL
were enrolled. Treatment with tadalafil significantly improved IPSS total score,
IPSS voiding subscore, IPSS storage subscore, OABSS and IPSS-QoL score after 4
weeks and these improvements were maintained for 12-week treatment period. IIEF5
score and general health in SF-8 are significantly improved with the treatment of
tadalafil. However, maximum flow rate and postvoiding residual volume were not
significantly changed. There were not any serious adverse events. CONCLUSIONS:
These results indicate that tadalafil 5 mg once daily would be effective and well
tolerated treatment in Japanese men with BPH-LUTS.
PMID- 29341502
TI - Advances in intravesical therapy for bladder pain syndrome (BPS)/interstitial
cystitis (IC).
AB - Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a chronic symptom
complex that may cause bothersome storage symptoms and pain or discomfort of the
bladder, adversely affecting a patient's quality of life. The etiology of IC/BPS
remains unclear, and its cause may be multifactorial. Diagnosis of IC/BPS is
based on clinical features, and the possibility of other conditions must be ruled
out first. Although no definitive treatment is currently available for IC/BPS,
various intravesical therapies are used for IC/BPS, including heparin, hyaluronic
acid, chondroitin sulfate, pentosan polysulfate, dimethylsulfoxide, liposomes,
and botulinum onabotulinumtoxinA (BoNT-A). This review summarizes the
intravesical therapy for IC/BPS and discusses recent advances in the instillation
of liposomal-mediated BoNT-A and other newly developed intravesical therapies.
PMID- 29341503
TI - Tadalafil 5 mg Once Daily Improves Lower Urinary Tract Symptoms and Erectile
Dysfunction: A Systematic Review and Meta-analysis.
AB - OBJECTIVES: We carried out a systematic review and meta-analysis to assess
tadalafil 5 mg once-daily for the treatment of lower urinary tract symptoms
(LUTS) and erectile dysfunction (ED). METHODS: A literature review was performed
to identify all published randomized double-blind, placebo-controlled trials of
tadalafil 5 mg once-daily for the treatment of LUTS and ED. The search included
the following databases: MEDLINE, EMBASE, and the Cochrane Controlled Trials
Register. The reference lists of the retrieved studies were also investigated.
RESULTS: Thirteen publications involving a total of 3973 patients were used in
the analysis, including 13 RCTs that compared tadalafil 5 mg once-daily with
placebo. We found that tadalafil 5 mg once-daily was effective in improving LUTS
suggestive of BPH and treating ED over 12 weeks in our meta-analysis. Total
International Prostate Symptom Score (IPSS) (SMD = - 2.02, 95% CI = - 2.52 to
1.53, P < 0.00001); Benign Prostatic Hyperplasia Impact Index (BPH-II) (SMD =
0.58, 95% CI = -0.84 to -0.33, P < 0.00001); International Index of Erectile
Function-erectile function (IIEF) domain (standardized mean difference [SMD] =
5.18, 95% confidence interval [CI] = 4.13-6.23, P < 0.00001) indicated that
tadalafil 5 mg once-daily was more effective than the placebo. Safety assessments
included discontinuations due to adverse event (odds ratio (OR) = 1.79, 95% CI =
1.12-2.85, P = 0.01) indicated that tadalafil 5 mg once-daily was well tolerated.
CONCLUSIONS: This meta-analysis indicates that tadalafil 5 mg once-daily to be an
effective treatment for LUTS and ED with a low occurrence of side effects.
PMID- 29341504
TI - A multi-institutional analysis of children on long-term non-invasive respiratory
support and their outcomes.
AB - OBJECTIVES: To characterize a multi-institutional cohort of children with chronic
respiratory failure that use long-term, non-invasive respiratory support, perform
a time-to-event analysis of transitions to transtracheal ventilation and identify
factors associated with earlier transition to transtracheal ventilation. STUDY
DESIGN: A retrospective cohort study of patients less than 21 years of age with
diagnoses associated with chronic respiratory failure and discharged on non
invasive respiratory support was performed using data from the Pediatric Health
Information System (PHIS) between 2007 and 2015. Demographic and clinical
characteristics, as well as times from index discharge on non-invasive support to
transtracheal ventilation were presented. A competing risk regression model was
fitted to estimate factors associated with earlier transition to transtracheal
ventilation. RESULTS: A total of 3802 patients were identified. Their median age
at index discharge was 10.4 years (interquartile range [IQR] 4.1-14.9). Of these
patients, 337 (8.9%) transitioned to transtracheal ventilation and transitioned
at a median of 11.5 months (IQR 4.6-26) post-index discharge, or a median age of
9.3 years (IQR 4.2-14.5). Competing risk modeling demonstrated that patients who
were older or whose discharge occurred later in the study period had lower
hazards of earlier transition to transtracheal ventilation, whereas patients with
anoxia/encephalopathy and quadriplegia had higher hazards of earlier
transitioning. CONCLUSIONS: Most patients on long-term, non-invasive respiratory
support who progress to transtracheal ventilation transition do so within a few
years of support initiation. Various characteristics were associated with earlier
risk of transitioning to transtracheal ventilation. This information may enhance
anticipatory guidance for this population.
PMID- 29341505
TI - Stability, integrity, and recovery rate of cellular nucleic acids preserved in a
new liquid-based cytology medium.
AB - BACKGROUND: Liquid-based cytology (LBC) has replaced the conventional
Papanicolaou test in cervical cancer screening. The cervical swab specimens
collected in LBC media can also be used for additional analyses including high
risk HPV (HR-HPV) test, DNA methylation analysis, and HPV E6/E7 mRNA test.
METHODS: The stability, integrity, and recovery rate of cellular DNA and RNA
after storage at different conditions were evaluated by a quantitative real-time
PCR (qPCR) based HR-HPV test, reverse transcription qPCR (RT-qPCR), and agarose
gel electrophoresis. Cervical swab specimens collected in a newly developed LBC
medium, VersaMedium, and ThinPrep PreservCyt medium were processed on Hologic
ThinPrep 5000 instrument. RESULTS: Cervical exfoliative cells fixed by
VersaMedium exhibited good cellular morphology with intact membranes and
delineated chromatin structures. Cellular DNA preserved in VersaMedium exhibited
high level of stability at both room temperature and 4 degrees C, and remained
mostly intact at 4 degrees C for up to 28 days. Cellular RNA preserved in
VersaMedium maintained higher level of stability and integrity at 4 degrees C
than at room temperature. VersaMedium also showed no apparent adverse effect on
the recovery rate of nucleic acids. CONCLUSION: In addition to maintaining
cellular morphology, when stored at 4 degrees C, VersaMedium preserves cellular
nucleic acids and PreservCyt medium without noticeable adverse effects on the
recovery rate during purification. Therefore, VersaMedium is an appropriate LBC
medium for the collection and preservation of cervical swab specimens. And
VersaMedium preserved cellular nucleic acids are of such high quality that they
are suitable for HR-HPV qPCR test and RT-qPCR analyses.
PMID- 29341507
TI - Residents Rosters: Reversal to Longer Hours in the US.
PMID- 29341508
TI - Delirium and the acute hospital system of the Republic of Ireland: Challenges,
solutions and opportunities.
PMID- 29341506
TI - Impact of preoperative anemia on outcomes in patients undergoing curative
resection for gastric cancer: a single-institution retrospective analysis of 2163
Chinese patients.
AB - We sought to evaluate whether preoperative anemia was an important determinant of
survival in gastric cancer (GC). A single institution cohort of 2163 GC patients
who underwent curative resection were retrospectively analyzed. Anemia was
defined as a preoperative hemoglobin level <120 g/L in males and <110 g/L in
females. Overall survival (OS) was analyzed using the Kaplan-Meier method, and a
multivariate Cox proportional hazards model was performed to identify the
independent prognostic factor. Anemic patients had a poorer OS compared with
nonanemic patients after resection for tumor-nodes-metastasis (TNM) stage III
tumors (5-year OS rate: 32.2% vs. 45.7%, P < 0.001) but not stage I (P = 0.480)
or stage II (P = 0.917) tumors. Multivariate analysis revealed that
preoperative anemia was an independent prognostic factor in TNM stage III (hazard
ratio [HR], 1.771; 95% CI, 1.040-3.015; P = 0.035). In a stage-stratified
analysis, preoperative anemia was still independently associated with OS in TNM
stages IIIa through IIIc (P < 0.001, P = 0.075, and P = 0.012, respectively),
though the association was only marginal in stage IIIb. Of note, preoperative
mild anemia had a similar prognostic value in TNM stage III GC. Furthermore,
preoperative anemia was significantly associated with more perioperative
transfusions, postoperative complications and several nutritional-based indices,
including the prognostic nutritional index (PNI), preoperative weight loss and
performance status (all P < 0.05). Preoperative anemia, even mild anemia, was an
important predictor of postoperative survival for TNM stage III GC.
PMID- 29341509
TI - Effect of the 2008 economic crisis on the cardiovascular mortality of the Irish
population: an ecological 12-year study of a heart-broken Celtic Tiger.
AB - Ireland has endured a substantial financial crisis in 2008 and we sought to
explore the effect of economic recession on Irish cardiovascular mortality. We
found an increase by 17.2% in CVA-deaths during the financial crisis years (95%
CI 11.1% to 23.6%). In males, we found a notable rise in the annual IHD rate by
7.56% (95% CI 4.73% to 10.46%), in annual MI rate by 2.96% (95% CI 0.16% to
5.84%), and in annual CVA death rate by 20.07% (95% CI 16.13% to 24.14%). In
females our findings indicated an increased rate of CVA-related deaths during the
economic crisis by 15.54% (95% CI 6.67% to 25.16%). Irish CVA-related deaths
increased during the economic crisis for males and females alike. Male IHD
related deaths have also risen indicating a potential differential effect for
financial hardships on male gender mortality.
PMID- 29341510
TI - Maternity Ultrasound in the Republic of Ireland 2016; A Review.
AB - Antenatal ultrasound, comprising of a dating ultrasound in the late first
trimester followed by a fetal anomaly scan, is a recognised and necessary
component of good antenatal care. We conducted a telephone survey of all 19
obstetric units to ascertain the status of maternity ultrasound provision in
Ireland. Fetal anomaly ultrasound is offered universally to all women in 7/19
(37%) units, selectively to some women in 7/19 (37%) units and not offered at all
in the remaining 5/19 (26%) units. Overall ? 41,700 (64%) women receive a fetal
anomaly ultrasound nationally. Universal first trimester ultrasound, performed in
a dedicated ultrasound department by a suitably qualified sonographer, is offered
to 47% of women nationally. This study highlights the lack of development in
Irish maternity ultrasound services over the last decade. Substantial investment
by health care policy makers is urgently needed.
PMID- 29341511
TI - Age Adjusted D-Dimer for exclusion of Pulmonary Embolism: a retrospective cohort
study.
AB - D-Dimer (DD) will increase with age and recent studies have shown the upper limit
of normal can be raised in those who are low risk and over 50. We studied age
adjusted D-dimer (AADD) levels to assess whether pulmonary embolism (PE) could be
safely excluded. This study analysed the Emergency Department (ED) Computed
Tomographic Pulmonary Angiography (CTPA) requests. There were 756 requests. The
parameters studied were; age, DD value, calculated AADD, CT result and Simplified
Geneva Score (SGS). The primary outcome was the diagnostic performance of AADD.
One hundred and eighty-five patients were included in the final cohort. Twenty
one patients had a negative DD after age adjustment. Of these one had a PE,
corresponding to a failure rate of 4.76% (1 in 22). The sensitivity of AADD was
0.96 (95% CI 0.76 to 0.99) and its specificity was 0.12 (95% CI 0.08- 0.19). AADD
demonstrated a reduction in false positives with one false negative, giving rise
to a failure rate higher than that of other larger studies. Further study is
indicated to accurately define the diagnostic characteristics for the Irish
context.
PMID- 29341512
TI - Food Allergy Emergencies in Children - To what extent are Early Years Services
Prepared? A cross-sectional survey.
AB - Food allergies are common in preschool children. This study's aims are to
establish prevalence, to clarify management practices, levels of preparedness and
the perceived role of General Practitioners amongst Early Years Services
providers. This study is an anonymous, quantitative, cross sectional study. An
online questionnaire was distributed to 282 Early Years Service providers. Data
were analysed using SPSS. Response rate was 35% (n=98). Prevalence of food
allergy was 3% (n=119). Allergic reactions to food had occurred on site in 16%
(n=15). Written emergency action plans were available in 47% of facilities
(n=46). Medications were not kept on site in 63% (n=62) of facilities. General
practitioners were felt to have an important role in the management of food
allergies by 76% of respondents (n=61). This study identifies significant areas
for improvement in the management of food allergic child in Early Years Services.
PMID- 29341513
TI - Investment in epilepsy monitoring units improves epilepsy care-experience in a
regional neuroscience centre.
AB - An evaluation of the clinical yield of inpatient long-term video-EEG (vEEG) in a
new epilepsy monitoring unit (EMU) was undertaken, with findings compared to the
centre's prior method of bedside vEEG recording in a standard neurology ward, as
reported in 2004. A retrospective analysis of neurophysiology reports for all
adults who underwent elective vEEG monitoring in the EMU at Cork University
Hospital between January 2015 and July 2016 was conducted. Of 115 vEEG studies in
the EMU, 100 (87.0%) were deemed diagnostically conclusive, 14 (12.2%) failed to
catch any clinical events and showed normal EEG throughout, and one (0.9%)
captured spells of unclear clinical significance - the corresponding figures
reported in 2004 for bedside vEEGs were 21.3%, 77% and 1.6%, respectively. The
EMU offers a more effective method of recording inpatient vEEG, which aids
decision-making and improves clinical outcomes. Some evidence-based measures
which could further enhance diagnostic yield are discussed.
PMID- 29341514
TI - Opportunity Costs in Paediatric Training: The Specialist Registrars Experience.
AB - In the training process, there is a tension between the work life and home life
of trainees. This study explored both the personal impact and the opportunity
costs of training from the Specialist Paediatric Registrar (SPR) perspective. The
survey explored 1) career progression, 2) perceived functional effectiveness at
work, 3) psychological impact of hospital based training, and 4) the personal and
social cost of training. Fifty-three (71%) SPRs responded of whom 47 (89%)were
married or in long term relationships. Seventy-five percent of trainees had a
definite career plan with 86% intending to undertake fellowship training. Seventy
percent believed they were efficient time managers but 53% had difficulty in
making time for academic pursuits and fifty percent experienced negative
feelings, which lingered after work and interfered with their relationships at
home. Seventy-four percent stated training was undertaken at significant personal
cost with only 21% achieving a very satisfactory work/life balance. To address
these difficulties trainee wellbeing should be addressed at the Basic Specialist
Training (BST) level and the career path clearly explained outlining the
challenges that are likely to be encountered.
PMID- 29341515
TI - The Uptake of Human Papillomavirus Vaccine In Irish Schools: The Impact Of
Disadvantage.
AB - HPV vaccine Gardasil(c) is offered to girls in first year of secondary school in
Ireland. We aimed to determine the association between HPV vaccine uptake among
girls for academic year 2013/2014, by school and school characteristics:
socioeconomic disadvantage and religious ethos. The National Schools Immunisation
System (SIS) was searched to determine HPV vaccine uptake in schools for
2013/2014 (prior to recent anti-HPV vaccine publicity). The disadvantaged status
and ethos of each school was added to the report. In total 577 schools were
identified. Mean vaccine uptake was 83.7%. Disadvantaged schools had a lower mean
uptake (%) than other schools (79.4% vs 85.0%, difference 5.58%, 95%CI 2.69-8.21)
and were twice as likely to have an uptake of ?50% (OR 2.07, 95% CI 2.76 - 5.18).
No difference was found between schools of different ethoses. HPV vaccine uptake
is lower in disadvantaged Irish schools. Policies should be developed to ensure a
more equitable uptake of HPV vaccine.
PMID- 29341516
TI - Epithelioid Angiomyolipoma - a case report and review of the literature.
AB - Herein we present the case of a 43-year-old female in whom a left renal mass was
identified incidentally on imaging performed for staging of a newly diagnosed
breast carcinoma. The mass was resected and histologic examination and
immunohistochemistry confirmed a diagnosis of epithelioid angiomyolipoma.
PMID- 29341517
TI - Proliferative myositis of the latissimus dorsi presenting in a 20-year-old male
athlete.
AB - We describe the case of a 20-year-old rower presenting with an uncommon condition
of Proliferative Myositis (PM) affecting the Latissimus Dorsi (LD). PM is a rare,
benign tumour infrequently developing in the upper back. Its rapid growth and
firm consistency may mistake it for sarcoma at presentation. Therefore, careful
multidisciplinary work-up is crucial, and should involve appropriate radiological
and histopathological investigations. Here, we propose the aetiology of LD PM to
be persistent myotrauma induced by repetitive rowing motions. Symptoms and rate
of progression ultimately determine the management which includes surveillance
and/or conservative resection. There have been no documented cases of recurrence
or malignant transformation.
PMID- 29341518
TI - Harlequin Ichthyosis - A Case Report.
AB - Harlequin Ichthyosis is a very rare genetic disorder affecting mainly the skin
with severe morbidity and mortality. It affects both sexes with incidence of
about 1 in 300,000 live births. Autosomal recessive inheritance has been inferred
with mutation in ABCA 12 gene identified. Hence, genetic counseling and mutation
screening of this gene should be considered in at-risk patients. Death usually
occurred in the first 3 months of life due to sepsis, feeding problems and
respiratory distress. With improved neonatal care and early introduction of
retinoids, its survival rate has increased.
PMID- 29341519
TI - Pelvic and acetabular trauma care in Ireland: the past, present and future.
PMID- 29341520
TI - Reclassification of Category 1-Caesarean Section.
PMID- 29341521
TI - 2015-2016 Influenza Season in an Irish Regional Paediatric Unit: Importance of
Influenza Vaccination Highlighted.
PMID- 29341522
TI - Echo Requests in light of Appropriate Use Criteria.
PMID- 29341523
TI - ?
PMID- 29341524
TI - [What's new in Ambulatory General Internal Medicine ?]
AB - Many treatments are used every day in general medicine without any evidence of
their efficacy. This last year, three randomised studies tried to prove the
clinical utility of chondroitin/glucosamine in arthritis, cranberry in urinary
infections, and acupuncture in migraine. Screening and management of prostate
cancer are still controversial. Two recent studies help us advising our patients
on this difficult topic. Muscle side effects from statins are well known and have
been widely relayed by the press these last years, although myopathies are rare
in clinical trials. A new study try to determine if negative expectations could
favor such adverse events.
PMID- 29341525
TI - [General internal medicine : 2017 scientific breakthroughs in ambulatory care].
AB - Bariatric surgery improves glycemic control in obese patients with diabetes type
2. Dual antiplatelet therapy can be maintained beyond 12 months after a
myocardial infarction. Levothyroxine is not beneficial among patients >= 65 years
that have subclinical hypothyroidism. Prophylactic anticoagulation in lower limb
immobilisation should be reserved only for patients with a high risk of
thromboembolism. A diagnosis of asthma should be initially confirmed by a
spirometry if clinically suspected. A proton pump inhibitor is indicated for
patients >= 65 years that are treated with aspirin. Beta-lactams should not be
avoided in patients with a previous history of non-severe allergy. General
internists overestimate harms and benefits of common medical tests and
treatments.
PMID- 29341526
TI - [The internal medicine articles that struck us the most in 2017].
AB - 2017 has continued to bring important progress in all areas of internal medicine,
impacting our daily practice. From bedside screening for beta-lactam allergies,
to statins as primary prevention in the elderly, SGLT2 inhibitors in heart
failure, azithromycin in severe asthmatics and tofacitinib in ulcero-haemorrhagic
recto-colitis, internal medicine journals are full of novelties. Every year, the
chief residents of the CHUV internal medicine ward meet up to share their
readings: here is their selection of eleven articles, chosen, summarized and
commented for you.
PMID- 29341527
TI - [Recent advances in internal medicine].
AB - In medicine, there are progresses which radically transform practices, change
recommendations and win unanimous support in the medical community. There are
some which divide, questioning principles that seemed established. There are also
small advances, which can answer the questions that internists ask themselves in
the daily care of their patients. Here are several articles published in 2017,
read and commented for you by hospitalists, selected according to their impact on
the medical world.
PMID- 29341528
TI - [N-acetylcysteine : effective treatment in severe alcoholic hepatitis ?]
AB - The use of N-acetylcysteine is of unknown significance when it comes to acute
liver failure of other origin but for paracetamol overdose. Current data state
its beneficial use when added to standard treatment for acute alcoholic
hepatitis, whereas this attitude is less clear for hepatitis of variable other
origin. This review of literature attends to evaluate and reveal the possible
interest of adding N-acetylcysteine to standard care of acute liver failure due
to alcoholism or other non-paracetamol linked causes.
PMID- 29341529
TI - [When the ward overflows : the impact of outlying beds on patient care].
AB - Due to the chronic lack of beds in hospitals, patients are often hospitalized in
other departments (outlier patients), with a responsible physician working in
another department. This causes increased thromboembolics risks, nosocomial
infections, falls and delirium in the elderly, morbidity and mortality. Outlier
patients, compared to standard patients, stay longer in the emergency department
and their discharge documents are available later. Outlying is used daily in the
CHUV hospital and new strategies are elaborated to manage patient flow,
especially during the flu epidemic. The purpose of this article is to review the
literature on this subject.
PMID- 29341530
TI - ?
PMID- 29341531
TI - ?
PMID- 29341532
TI - ?
PMID- 29341533
TI - ?
PMID- 29341535
TI - ?
PMID- 29341534
TI - ?
PMID- 29341536
TI - ?
PMID- 29341538
TI - ?
PMID- 29341537
TI - ?
PMID- 29341539
TI - ?
PMID- 29341540
TI - ?
PMID- 29341541
TI - Radiotherapy fiber dosimeter probes based on silver-only coated hollow glass
waveguides.
AB - Manifestation of Cerenkov radiation as a contaminating signal is a significant
issue in radiation therapy dose measurement by fiber-coupled scintillator
dosimeters. To enhance the scintillation signal transmission while minimizing
Cerenkov radiation contamination, we designed a fiber probe using a silver-only
coated hollow waveguide (HWG). The HWG with scintillator inserted in its tip,
embedded in tissue-mimicking phantoms, was irradiated with clinical electron and
photon beams generated by a medical linear accelerator. Optical spectra of the
irradiated tip were taken using a fiber spectrometer, and the signal was
deconvolved with a linear fitting algorithm. The resultant decomposed spectra of
the scintillator with and without Cerenkov correction were in agreement with
measurements performed by a standard electron diode and ion chamber for electron
and photon beam dosimetry, respectively, indicating the minimal effect of
Cerenkov contamination in the HWG-based dosimeter. Furthermore, compared with a
silver/dielectric-coated HWG fiber dosimeter design, we observed higher signal
transmission in the design based on the use of silver-only HWG.
PMID- 29341542
TI - Intrinsic fluorescence for cervical precancer detection using polarized light
based in-house fabricated portable device.
AB - An in-house fabricated portable device has been tested to detect cervical
precancer through the intrinsic fluorescence from human cervix of the whole
uterus in a clinical setting. A previously validated technique based on
simultaneously acquired polarized fluorescence and polarized elastic scattering
spectra from a turbid medium is used to extract the intrinsic fluorescence. Using
a diode laser at 405 nm, intrinsic fluorescence of flavin adenine dinucleotide,
which is the dominant fluorophore and other contributing fluorophores in the
epithelium of cervical tissue, has been extracted. Different grades of cervical
precancer (cervical intraepithelial neoplasia; CIN) have been discriminated using
principal component analysis-based Mahalanobis distance and linear discriminant
analysis. Normal, CIN I and CIN II samples have been discriminated from one
another with high sensitivity and specificity at 95% confidence level. This ex
vivo study with cervix of whole uterus samples immediately after hysterectomy in
a clinical environment indicates that the in-house fabricated portable device has
the potential to be used as a screening tool for in vivo precancer detection
using intrinsic fluorescence.
PMID- 29341543
TI - Improved axial point spread function in a two-frequency laser scanning confocal
fluorescence microscope.
AB - A two-frequency laser scanning confocal fluorescence microscope (TF-LSCFM) based
on intensity modulated fluorescence signal detection was proposed. The specimen
induced spherical aberration and scattering effect were suppressed intrinsically,
and high image contrast was presented due to heterodyne interference. An improved
axial point spread function in a TF-LSCFM compared with a conventional laser
scanning confocal fluorescence microscope was demonstrated and discussed.
PMID- 29341544
TI - ?
PMID- 29341545
TI - ?
PMID- 29341546
TI - ?
PMID- 29341547
TI - ?
PMID- 29341548
TI - ?
PMID- 29341549
TI - ?
PMID- 29341550
TI - Health stewardship: a concept for best health outcomes.
AB - The concept of health stewardship and responsibility for self, marks a shift from
adopting a paternalistic approach to care, with decision-making the main remit of
healthcare practitioners, towards encouraging and empowering individuals to take
increasing responsibility for their healthcare and outcomes. The main aim of
nursing is to achieve optimal health outcomes for every patient. Exploring health
stewardship as a path to wellness will assist healthcare practitioners to guide
patients living with a chronic disease to be as healthy as possible.
PMID- 29341551
TI - Reflection on curative treatment versus palliation of symptoms in end of life
care.
AB - The conflicting tasks of treating or managing disease and preparing patients and
their families for the end of life are well documented in haematology and
palliative care settings. This article is a reflection on practice by a nursing
student who was in the fourth year of an internship, and discusses a case study
involving a woman at the end of life. It considers the approach to palliative and
end of life care adopted in an oncology and haematology ward where there was a
reluctance to be realistic about the limitations of treatments among some
healthcare practitioners, who did not want to dispel unrealistic expectations of
the patient's recovery as a result of continuing treatment. This reflection
focuses on the care of a patient at the end of life and the frustration
experienced by the nursing student at their inability to alter the direction of
treatment from curative treatment to the palliation of symptoms.
PMID- 29341552
TI - Developing the organisational culture in a healthcare setting.
AB - This article aims to define organisational culture and explain why it is
important to patients, carers and those working in healthcare environments.
Organisational culture is not a new concept and the literature on the subject is
well-established. However, because of the changing dynamics of the NHS, there has
been a shift away from 'what' the NHS stands for, often relating to its history
and rituals, to 'who' it functions for, including how healthcare professionals
such as nurses can develop and drive the organisational culture. The article
seeks to assist nurses in understanding the role of organisational culture, as
well as implementing its main principles in the workplace.
PMID- 29341553
TI - Pulmonary sequestration mimicring lun cancer: A case report.
AB - Introduction: Pulmonary sequestration is a rare congenital anomaly and most
intralobar sequestrations were located in lower lobes. Case report: We reported
an unusual 28-yearold female patient with intralobar pulmonary sequestration on
the left lower lobe, successfully treated with lobectomy. Computed tomography
(CT) of the chest with intravenous contrast revealed multiple clustered cystic
lesions in the left lower lobe with aberrant artery from descedenting aorta.
Additional aortography showed an aberrant artery (3 mm in diameter) arising from
the abdominal aorta and flowing into the lesion. Conclusion: Standard therapy
regimen for pulmonary sequestration includes surgery. CT scan of thorax with
intravenous contrast and aortography represent the gold standard for its
diagnosis. Tumor-like shadows seen on the chest radiography or CT scans should
not be always suspected on malignant lesions.
PMID- 29341554
TI - Hyperparathyroidism as a cause of recurrent acute pancreatitis: A case report.
AB - Introduction: One of the more uncommon etiological factors responsible for the
development of acute pancreatitis (AP) is hypercalcemia. Hyperparathyroidism
(HPT), as a cause of hypercalcemia, is responsible for 1.5-13% of AP according to
a number of studies. A mechanism of the development of AP in hyperparathyroidism
is still unclear. Case report: We presented a 47-year-old female patient, who had
five episodes of AP in total before the etiological factors were finally
determined. The patient had certain comorbidities which were considered to be
potential causes of AP. She had chronic renal insufficiency (she was on a regular
hemodialysis program), systemic lupus erythematosus and mioma uteri. She used to
regularly take an antiepileptic drug (combination of sodium valproate and
valproic acid). During the fifth episode of AP, the serum calcium level was for
the first time elevated to twice the normal value. Level of parathyroid hormone
was several times higher. A static scintigraphy found hyperplasia or
hyperfunctional adenoma of the right inferior and superior parathyroid glands.
Abdominal multislice computed tomography (MSCT) scan verified the enlargement of
the entire pancreas, as well as the presence of heterogeneous structures with
diffuse amorphous calcifications. The lytic lesions in the pelvic bones could be
seen in both sides. Parathyroidectomy was being postponed by an endocrine surgeon
because of the poor overall condition of the patient. In the next period the
patient had five more episodes of AP. The condition was significantly contributed
by increasingly more frequent and longer episodes of metrorrhagia. Despite all
therapeutic measures that were taken, systemic inflammatory response syndrome
(SIRS) developed, and fatal outcome occurred. Conclusion: In case of recurrent
pancreatitis, hyperparathyroidism is to be considered even if a significant
elevation of serum calcium is not present. This is especially the case for
patients with chronic renal insufficiency or impaired vitamin D metabolism, who
have a higher risk of secondary hyperthyroidism.
PMID- 29341561
TI - Massive fetomaternal hemorrhage as a cause of severe fetal anemia.
AB - Introduction: Fetomaternal hemorrhage (FMH) is a transfu-sion of fetal blood into
the maternal circulation. A volume of transfused fetal blood required to cause
severe, life-threatening fetal anemia, is not clearly defined. Some authors
suggest vol-umes of 80 mL and 150 mL as a threshold which defines mas-sive FMH.
Therefore, a rate of massive FMH is 1 : 1,000 and 1 : 5,000 births, respectively.
Fetal and neonatal anemia is one of the most serious complications of the FMH.
Clinical manifesta-tions of FMH are nonspecific, and mostly it presented as re
duced fetal movements and changes in cardiotocography (CTG). The standard for
diagnosing FMH is Kleihaurer-Betke test. Case report: A 34-year-old gravida (G)
1, para (P) 1 was hospitalized due to uterine contractions at 39 weeks of gesta
tion. CTG monitoring revealed sinusoidal fetal heart rate and clinical
examination showed complete cervical dilatation. Im-mediately after admission,
the women delivered vaginally. Ap-gar scores were 1 and 2 at the first and fifth
minute, respec-tively. Immediately baby was intubated and mechanical ventila-tion
started. Initial analysis revealed pronounced acidosis and severe anemia. The
patient received intravenous fluid therapy with sodium-bicarbonate as well as red
cell transfusion. With all measures, the condition of the baby improved with
normaliza-tion of hemoglobin level and blood pH. Kleihaurer-Betke test revealed
the presence of fetal red cells in maternal circulation, equivalent to 531 mL
blood loss. The level of maternal fetal hemoglobin (HbF) and elevated alpha
fetoprotein also con-firmed the diagnosis of massive FMH. Conclusion: For the
successful diagnosis and management of FMH direct commu-nication between the
obstetrician and the pediatrician is neces-sary as presented in this report.
PMID- 29341562
TI - Synchronous mantle cell lymphoma and prostate adenocarcinoma-is it just a
coincidence?
AB - Introduction: Synchronous occurrence of lymphomas and other cancers, mostly
carcinomas are well established. The most of cases describe chronic lymphocytic
leukemia as the leading lymphoproliferative disease with the tendency towards
secondary malignancies development. Mantle cell lymphoma (MCL) has been described
in only 2 cases to co-occur with prostate adenocarcinoma (PAC). There are scarce
data about the connection between MCL and urology cancers. We presented the first
case of synchronous occurrence of MCL and PAC in the same patient in Serbia. Case
report: A 64-year-old male initially presented with fatigue, splenomegaly, and
bicytopenia. The bone marrow biopsy specimen revealed extensive infiltration with
MCL. During lymphoma staging procedure prostate enlargement (57 mm) was
accidentally found by multislice- computed tomography (MSCT). The serum prostate
specific antigen (PSA) was elevated (52 ng/mL; normal values <= 4 ng/mL).
Transrectal ultrasound biopsy revealed PAC. High Gleason score determined high
risk locally advanced PAC. The patient underwent treatment with chemotherapy and
hormone therapy due to the existence of double malignancies. Cyclophosphamide,
doxorubicin, vincristine, prednisone (CHOP) was applied for MCL, and luteinizing
hormonereleasing hormone (LHRH) agonist, triptorelin, for PAC. Partial response
was obtained for MCL, and stable disease for PAC. In a 1.5-year observation
period the patient was still disease progression free for both of malignancies.
Conclusion: This case points aut that elderly males are in need for careful
observation during the staging procedure for lymphoma. The literature data
suggest that MCL patients are in increased risk for urologic malignancies
development. However, the etiologic connection between these two entities, except
male gender and older age, remains unclear.
PMID- 29341563
TI - Consumption of antihistamines in Serbia in the period 2011-2015 and the
correlation with adverse drug reaction reports.
PMID- 29341564
TI - FMR1 gene mutations cause neurodevelopmental-degenerative disorders: Importance
of fragile X testing in Serbia
PMID- 29341565
TI - Psoriasis is the independent factor for early atherosclerosis: A prospective
study of cardiometabolic risk profile.
AB - Background/Aim: Psoriasis as multisystemic inflammatory dis-ease is related with
an increased cardiometabolic risk. The aim of the study was to analyze risk
biomarkers, peripheral and renal arteries ultrasonography and echocardiography
for subclinical atherosclerosis and metabolic disease in 106 subjects (66
psoriasis patients and 40 controls, 20 eczema patients and 20 healthy
volunteers). Methods: In all exameenes following parameters were analyzed: body
mass index (BMI), C-reactive protein, D-dimer, serum amyloid A (SAA),
apolipoprotein (Apo) A1, ApoB, ApoB/Apo A1 index, fasting glucose, C-peptide,
fasting insulinemia, homeostatic model assessment-insulin resistance (HOMA-IR),
HOMA-beta-cell, lipid profile, serum uric acid concentration (SUAC), 24-h
proteinuria and microalbuminuria. Carotid, brachial, femoral and renal arteries
ultrasonography, as well as echocardiography was also performed. Results: Five of
66 (7.6%) psoriasis patients had metabolic syndrome (not present in both control
groups). The following variables were increased in patients with psoriasis
compared to both control groups: BMI (p = 0.012), insulinemia (p < 0.001), HOMA
IR (p = 0.003), HOMA-beta cell (p < 0.001), SUAC (p = 0.006), ApoB/ApoA1 ra-tio
(p = 0.006) and microalbuminuria (p < 0.001). Also, increased C-peptide (p =
0.034), D-dimer (p = 0.029), triglycerides (p = 0.044), SAA (p = 0.005) and
decreased ApoA1 (p = 0.014) were found in the psoriasis patients compared to
healthy controls. HDL cholesterol was decreased in the psoriasis patients
compared to the control group of eczema patients (p = 0.004). Common carotid
(CIMT) and femoral artery intima-media thickness (FIMT) was significantly greater
(p < 0.001) and the maximal flow speed (cm/s) in brachial artery significantly de
creased (p = 0.017) in the patients with psoriasis in comparison to both control
groups. In multivariate logistic regression analysis, after the adjustment for
confounding variables, the most important predictor of CIMT and FIMT was the
diagnosis of psoriasis (p < 0.001).. Conclusion: Cardiometabolic risk biomarkers
and ultrasonographic signs of early atherosclerosis are correlated with the
diagnosis of psoriasis, and not to generalized eczema. Psoriasis was found to be
an independent risk factor for subclinical atherosclerosis
PMID- 29341566
TI - Prevalence of dental caries in hospitalized patients with schizophrenia.
AB - Background/Aim: It is considered that over 450 million people worldwide suffer
from some form of mental disorder. Previous studies in other countries have shown
that schizophrenia is among the most frequent. Oral health is significant for
general health and should not be separated from mental health. Studies in other
countries have shown an increased incidence of carious and extracted teeth, and
less incidence of filled teeth in this group of psychiatric patients. The aim of
this study was to establish condition of the existing teeth, to determine the
prevalence of caries and to consider possible risk factors that contribute to the
current oral health status of hospitalized patients with schizophrenia. Methods:
The study comprised 190 patients with schizophrenia, hospitalized at the Clinic
for Psychiatric Disorders "Dr. Laza Lazarevic" in Belgrade, and 190 mentally
healthy patients at the Clinic for Periodontology and Oral Medicine, Faculty of
Dental Medicine in Belgrade. The decayed, missing, filled (DMF) index,
sociodemographic and economic characteristics were registered in both groups, as
well as characteristics of the primary disease of hospitalized patients with
schizophrenia. Results: The value of DMF index (representing the sum of carious,
extracted and filled teeth), in the hospitalized patients with schizophrenia was
18.57 +/- 7.07 and 12.47 +/- 5.64 in the healthy group (p = 0.000). The structure
of the DMF index in the study group showed that caries and extracted teeth
dominated with 88.1%; in the control group, filled teeth dominated with 55.6%,
which was a statistically significant difference for all the three observed
variables Conclusion: Hospitalized patients with schizophrenia had twice as many
caries and extracted teeth, and five time less filled teeth than healthy people.
The patient's age and taking antiparkinsonics were established as predictors of
the increased DMF index in hospitalized patients with schizophrenia.
PMID- 29341567
TI - Community-acquired urinary tract infections: Causative agents and their
resistance to antimicrobial drugs.
AB - Background/Aim: Urinary tract infections (UTIs) are among the most common
infections in outpatients. The aim of this study was to define the causative
agents of urinary tract infections and their resistance to antimicrobial drugs in
the urban area of central Serbia, as well as to evaluate eventual differences
associated with age and gender of the patients. Methods: This retrospective study
analysed data taken from routine, consecutively collected urine cultures of
outpatients with symptomatic UTIs, collected from the Department of Microbiology,
Institute of Public Health in Kragujevac, Serbia, from January 2009 to December
2013. Results: There were 71,905 urine cultures, and 24,713 (34.37%) of them were
positive for bacterial pathogens. The most common pathogen was Escherichia coli
(E. coli) (56.56%), followed by Klebsiella spp. (16.20%), Proteus spp. (14.68%),
Enterococcus spp. (5.29%) and Pseudomonas aeruginosa (3.74%). E. coli and
Enterococcus spp. isolation rates were lower in males >= 60 years old (23.71% and
4.87%, respectively), while Klebsiella spp. was more prevalent in this group
(32.06%). The most common causative agents isolated from 15-29 years old male
patients were Enterococcus spp. and Pseudomonas aeruginosa (13.28% each). Among
women, the isolation rate of E.coli was high in all age groups (around 70%).
Proteus spp. was frequently isolated from females <= 14 years old (13.27%), while
Klebsiella spp. was the most frequent in the oldest age female group (10.99%).
Conclusion: Choice of antibiotics for treatment of UTIs should be governed not
only by the local resistance patterns, but also by gender and age of patients.
PMID- 29341568
TI - Stigmatization and discrimination of patients with chronic hepatitis C.
AB - Background/Aim: Chronic hepatitis C (CHC) is often associated with injectable
drug users and human immunodeficiency virus coinfection for which there is
stigmatization in society. The aim of this study was to identify the presence of
stigma and discrimination of patients with CHC, as well as the influence of
sociodemographic factors on the occurrence of stigmatization. Methods: A cross
sectional study was performed. Patients with CHC and conducted antiviral therapy
completed an anonymous structured questionnaire consisting of sociodemographic
questions and Hepatitis C stigma scale. Results: Out of 154 patients 61.7% were
male and 72.1% from the city; 59.7% have completed secondary school; 61.7% were
employed before the disease while 31.8% after the disease; 45.5% were
unsatisfactory with financial situation; 54.5% were married; 37.7% lived with a
spouse and children; 86.4% in their own house/apartment; 5.2% of the patients
were abandoned by their partners, while 35.7% consumed drugs. A statistical
significance of the stigma score was found in those who lived in the city (p =
0.018), unmarried (p = 0.005), abandoned by the partners after the diagnosis of
CHC (p < 0.001), drug users (p = 0.002) and those living with parents (p =
0.034). Univariate regression analysis singled out as significant: residence (p =
0.018), living with their parents (p = 0.046), abandonment by a partner (p <
0.001) and drug use (p = 0.002). A multivariate regression model of independent
variables singled out abandonment by partners (Beta = 5.158, p = 0.007). Men
disagree significantly with the two elements inside stigma [not the same as the
others (p = 0.035)] and hurt by the reaction of others (p = 0.047)). Conclusion:
The presence of stigma in patients with CHC was proven. The results indicate the
need to strengthen anti-stigma programs that will reduce their psychological and
social problems and reduce stigmatization in society.
PMID- 29341569
TI - Agreement between admission and discharge diagnoses: Analysis by the groups of
international classification of diseases, 10th revision.
AB - Background/Aim: Admission diagnosis represents the diagnosis of an illness,
injury or condition due to which a patient is referred to hospital to be
admitted. Discharge diagnosis represents the main reason of illness or condition
due to which a patient is admitted. The aim of this study was to analyze the
agreement between admission diagnostic groups and discharge diagnostic groups of
patients in the Clinical Center Kragujevac in the period from January 1, 2006 to
December 31, 2013 on the basis of the hospitalization report. Methods: From the
basic set of reports, 5% of random samples were singled out and they contained
20,422 reports. Out of the given number of reports, 18,173 hospitalization
reports were complete and then further analyzed in the paper. Admission
diagnostic groups given by the primary care doctor were compared with discharge
diagnostic groups filled out by the practicing physician in the hospital ward
from which a patient was discharged. The agreement of these two diagnostic groups
was an indication of the high-quality performance of the primary care doctor.
Agreement analysis was conducted using Cohen's Kappa statistics. Restuls:
Agreement analysis showed that the values of the Kappa coefficient for the five
leading admission diagnostic groups were in the range of kappa = 0.61 to kappa =
0.94. The values of the Kappa coefficient for the five most common discharge
diagnostic groups were in the range of kappa = 0.55 to kappa = 0.81. Conclusion:
Hospitalization report is a reliable individual report on inpatient care, so it
could be used in determining the degree of agreement between admission diagnostic
groups and discharge diagnostic groups.
PMID- 29341570
TI - Histomorphometric evaluation of bone regeneration using autogenous bone and beta
tricalcium phosphate in diabetic rabbits.
AB - Background/Aim: The mechanism of impaired bone healing in diabetes mellitus
includes different tissue and cellular level activities due to micro- and
macrovascular changes. As a chronic metabolic disease with vascular
complications, diabetes affects a process of bone regeneration as well. The
therapeutic approach in bone regeneration is based on the use of osteoinductive
autogenous grafts as well as osteoconductive synthetic material, like a beta
tricalcium phosphate. The aim of the study was to determine the quality and
quantity of new bone formation after the use of autogenous bone and beta
tricalcium phosphate in the model of calvarial critical-sized defect in rabbits
with induced diabetes mellitus type I. Methods: The study included eight 4-month
old Chincilla rabbits with alloxan-induced diabetes mellitus type I. In all
animals, there were surgically created two calvarial bilateral defects (diameter
12 mm), which were grafted with autogenous bone and beta-tricalcium phosphate (n
= 4) or served as unfilled controls (n = 4). After 4 weeks of healing, animals
were sacrificed and calvarial bone blocks were taken for histologic and
histomorphometric analysis. Beside descriptive histologic evaluation, the
percentage of new bone formation, connective tissue and residual graft were
calculated. All parameters were statistically evaluated by Friedman Test and post
hock Wilcoxon Singed Ranks Test with a significance of p < 0.05. Results:
Histology revealed active new bone formation peripherally with centrally located
connective tissue, newly formed woven bone and well incorporated residual grafts
in all treated defects. Control samples showed no bone bridging of defects. There
was a significantly more new bone in autogeonous graft (53%) compared with beta
tricalcium phosphate (30%), (p < 0.030) and control (7%), (p < 0.000) groups. A
significant difference was also recorded between beta-tricalcium phosphate and
control groups (p < 0.008). Conclusion: In the present study on the rabbit
grafting model with induced diabetes mellitus type I, the effective bone
regeneration of critical bone defects was obtained using autogenous bone graft.
[Projekat Ministarstva nauke Republike Srbije, br. 175021].
PMID- 29341571
TI - Diagnostic accuracy of the A-test and cutoff points for assessing outcomes and
planning acute and post-acute rehabilitation of patients surgically treated for
hip fractures and osteoarthritis.
AB - Background/Aim: The A-test is used in daily clinical practice for monitoring
functional recovery of orthopedic patients during early rehabilitation. The aim
of this study was to determine the accuracy of A-test and cutoff point at which
the test can separate patients with and without functional disability at the end
of early rehabilitation. Also, it was important to determine whether A-test has
that discriminative ability (and at which cutoff points) in the first days of
early rehabilitation in order to have time to plan post acute rehabilitation.
Methods: This measurement-focused study was conducted in the Orthopedic Ward
during early inpatient rehabilitation (1st-5th day after the operation) of 60
patients with hip osteoarthritis (HO) that underwent arthroplasty and 60
surgically treated patients with hip fracture (HF). For measurements we used the
A-test and the University of Iowa Level of Assistance Scale (ILAS) as the gold
standard. For statistical analysis we used the receiver operating characteristic
(ROC) curve and the area under the curve (AUC) with 95% confidence interval for
the results of A-test from the first to the fifth day of rehabilitation,
sensitivity, specificity, the rate of false positive and false negative errors,
positive and negative predictive value, ratio of positive and negative likelihood
ratio, accuracy, point to the ROC curve closest to 0.1 and Youden index for all
the cutoff points. Results: The AUC was 0.825 (0.744-0.905) for the first day of
rehabilitation, 0.922 (0.872-0.972) for the second day of rehabilitation, 0.980
(0.959-1.000) for the third day of rehabilitation, 0.989 (0.973-1.004) for the
fourth day, and 0.999 (0.996-1.001) for the fifth day of rehabilitation. The
optimal cutoff for the results of A-test was: 7/8 for the first day, 29/30 for
the fourth day, and 34/35 for the fifth day of rehabilitation. On the second and
the third day A-test had two cutoff points, the lower point safely separated the
patients with functional disability, while the upper point ruled out functional
disability. On the 2nd rehabilitation day the cutoff points were 12/13 and 17/18,
on the 3rd rehabilitation day cutoff points were 13/14 and 18/19. Conclusion: The
A-test has all characteristics of an accurate tool which can be used for
separating patients with and without functional disability at all stages of early
rehabilitation after surgically treated hip disease or fracture. Based on the
results of A-test within the first days of early rehabilitation, it is possible
to make a plan for postacute rehabilitation.
PMID- 29341572
TI - Risk factors for cardiovascular disease in children on chronic hemodialysis:
Traditional (general) risk factors, Part I.
PMID- 29341573
TI - Classification and the diagnostics of abnormal uterine bleeding in nongravid
women of reproductive age: The PALM-COEIN classification system adopted by the
International Federation of Gynecology and Obstetrics.
PMID- 29341574
TI - Bullous lung diseases as a risk factor for lung cancer: A case report.
AB - Introduction: A possible association between lung cancer and bullous lung disease
has been suggested and recently supported by the results of genetic studies. Case
report: A previously healthy 43-year-old man, smoker, was diagnosed with bullous
lung disease at the age of 31 years. He was followed up for 12 years when lung
cancer (adenocarcinoma) was found at the site. In the meantime, he was treated
for recurrent respiratory infections. Conclusion: There is the need for active
approach in following up the patients with pulmonary bulla for potential
development of lung cancer.
PMID- 29341575
TI - Severe vaso-occlusive retinopathy associated with systemic lupus erythematosus.
AB - Introduction: Systemic lupus erythematosus (SLE) is a systemic idiopathic
autoimmune inflammatory disease, with multiple organ involvement. Severe vaso
occlusive retinopathy is a rare, sight threatening lupus-related manifestation of
the disease, which is more common in patients with coexisting antiphospholipid
syndrome. Case report: We reported a 36-year-old female with severe vaso
occlusive retinopathy that manifested in the absence of antiphospholipid
syndrome. In a 4-year follow-up, despite aggressive systemic corticosteroid and
immunosuppressive therapy and panretinal laserphotocoagulation treatment, the
disease progressed to retinal neovascularisation, neovascular vitreoretinopathy,
neovascular glaucoma and, consecutively, severe visual loss. As the final option
for preservation of visual function, pars plana vitrectomy with
laserphotocoagulation was performed and had good results. Progression of
ophthalmological findings indicated the progression of the systemic disease, as
well as neurolupus. Conclusion: Severe vaso-occlusive retinopathy occurred as the
ophthalmological manifestation of SLE in the absence of antiphospholipid
syndrome, but correlated with neurolupus and led to visual deterioration despite
the treatment.
PMID- 29341576
TI - Pseudomesotheliomatous carcinoma of the lung.
AB - Introduction: Pseudomesotheliomatous lung carcinoma is a special, rare entity
characterized by large pleural growth and minor invasion of lung tissue.
Clinically, radiologically, macroscopically and even histologically this tumor
can be misdiagnosed as malignant pleural carcinoma. Case report: We represent a
64-year-old male patient, former smoker. Due to difficulties in the form of dry
cough, feeling of dis-comfort and pain in the right hemithorax, fatigue, heavy
breathing, sweating, fever up to 39.6 degrees C the patient was treated as with
combined antibiotic therapy (macrolides, cephalosporins and penicillin), but
without improving of his condition. Chest radiography showed a shadow of pleural
effusion by the height of the front end of the third right rib. Chest MSCT showed
the extremely thickened pleura apically and to the posterior along the upper
right lobe in addition to existence of massive pleural effusion. Subpleural
condensation of parenchyma ranging about 30 mm was described in the upper right
lobe. Cytological analysis of the pleural effusion showed the presence of
malignant cells impossible to differentiate whether they were metastasis of
adenocarcinoma or malignant pleural mesothelioma. By histochemical and
immunohistohemical analyses of a pleural sample, pseudomesotheliomataus lung
adenocarcinoma was diagnosed. Conclusion: Pseudomesotheliomataus carcinoma of the
lungs can be a diagnostic problem. Its diagnosis is based on recognition of
histopathological characteristics which enable its discernment from the
epithelial variant of malignant pleural mesothelioma.
PMID- 29341577
TI - Apical root-end filling with tricalcium silicate-based cement in a patient with
diabetes mellitus: A case report.
AB - Introduction: The material used for root-end filling has to be biocompatible with
adjacent periapical tissue and to stimulate its regenerative processes.
Tricalcium silicate cement (TSC), as a new dental material, shows good sealing
properties with dentin, high compression strengths and better marginal adaptation
than commonly used root-end filling materials. Although optimal postoperative
healing of periapical tissues is mainly influenced by characteristics of end-root
material used, it could sometimes be affected by the influence of systemic
diseases, such as diabetes mellitus (DM). Case report: We presented apical
healing of the upper central incisor, retrofilled with TSC, in a diabetic patient
(type 2 DM) with peripheral neuropathy. Standard root-end resection of upper
central incisor was accompanied by retropreparation using ultrasonic retrotips to
the depth of 3 mm and retrofilling with TSC. Post-operatively, the surgical wound
healed uneventfully. However, the patient reported undefined dull pain in the
operated area that could possibly be attributed to undiagnosed intraoral diabetic
peripheral neuropathy, what was evaluated clinically. Conclusion: Although TSC
presents a suitable material for apical root-end filling in the treatment of
chronic periradicular lesions a possible presence of systemic diseases, like type
2 DM, has to be considered in the treatment outcome estimation.
PMID- 29341578
TI - Case report of gross hematuria in the nutcracker syndrome resolved by renocaval
reimplantation.
AB - Introduction: Nutcracker syndrome is defined as a set of signs and symptoms
secondary to compression of the left renal vein (LRV) in the acute anatomic angle
between the aorta and its superior mesenteric branch. Case report: A 38-year old
woman with asymptomatic and "idiopathic" gross hematuria came to the Clinic for
Vascular and Endovascular Surgery, Clinical Center of Serbia in Belgrade.
Hematuria was documented by cystoscopy and was found to be unilateral, located to
the left urethral orifice. The contrast-enhanced multidetector computed
tomography (MDCT) scan showed a stenotic LRV due to the extrinsic compression in
the angle formed by the ventral aorta and superior mesenteric artery (MSA), with
a jet of contrast through the lumen. Considering the negative investigations for
more common causes of hematuria, its incapacitating nature, and above mentioned
imaging findings suggestive of the nutcracker syndrome, an indication for the
open surgical correction of the LRV entrapment was established. The patient
underwent reimplantation of the LRV into the more distal inferior vena cava
(IVC), to relocate it out of the constrictive aortomesenteric space.
Intraoperative findings were notable for blood flow turbulence in the LRV and
hypertrophy of its tributaries, which were ligated. We presented the first
published case in the Serbian literature on nutcracker syndrome with hematuria
resolved by renocaval reimplantation. Conclusion: This case report demonstrates
that renocaval reimplantation, as the open surgery technique, could be the
adequate method for resolving gross hematuria in patients with nutcracker
syndrome.
PMID- 29341579
TI - Nanoparticulate Contrast Agents for Multimodality Molecular Imaging.
AB - Molecular imaging is rapidly developing as a powerful tool in research and
medical diagnostic. By integrating complementary signal reporters into a single
nanoparticulate contrast agent, multimodal molecular imaging can be performed as
scalable images with high sensitivity, resolution and specificity. In this
review, multifunctional nanoparticles (MFNPs) are classified into four types:
conjugation, encapsulation, core/shell, and co-doping. Further, new constructs of
MFNPs were reported recently which have used nanoparticulate contrast agent such
as quantum dots (QDs), iron oxide nanoparticles (IONPs), Upconversion
nanoparticles (UCNPs), carbon based nanoparticles, gold nanoparticles (Au-NPs),
Metal-Organic Frameworks (MOFs), dendrimers and porphyrins based nanoparticles.
Different surface modification strategies were also developed as well as ligands
are attached to those NPs to render the biocompatibility and enable specific
targeting. These new development in MFNPs are expected to introduce a paradigm
shift in multi-modal molecular imaging and thereby opening up an era of
personalized medicine and new diagnostic medical imaging tools.
PMID- 29341580
TI - Hippocrates-The father of modern medicine.
PMID- 29341581
TI - Functional Chitosan Nanoparticles in Cancer Treatment.
AB - With exponential growth in nanotechnology and material chemistry, the application
of a variety of nanomaterials in biomedical field has attracted increasing
interest, especially in cancer diagnosis and treatment. Nanoparticles have
greatly revolutionized the therapy pattern of cancer owing to their specific
targeting ability, prolonged circulation time, enhanced therapeutic efficacy, and
decreased systemic side effects. Chitosan, a modified natural polysaccharide with
excellent biocompatibility, has been intensively studied for use as carriers to
deliver various drugs and genes in cancer treatment. This review provides an
insight into the advances in chitosan-based nanoparticles with a focus on its
therapeutic potential in cancer treatment.
PMID- 29341582
TI - In-Plane Channel-Structured Catalyst Layer for Polymer Electrolyte Membrane Fuel
Cells.
AB - In this study, we present a novel catalyst layer (CL) with in-plane flow channels
to enhance the mass transports in polymer electrolyte membrane fuel cells. The CL
with in-plane channels on its surface is fabricated by coating a CL slurry onto a
surface-treated substrate with the inverse line pattern and transferring the
dried CL from the substrate to a membrane. The membrane electrode assembly with
the in-plane channel-patterned CL has superior power performances in high current
densities compared with an unpatterned, flat CL, demonstrating a significant
enhancement of the mass-transport property by the in-plane channels carved in the
CL. The performance gain is more pronounced when the channel direction is
perpendicular to the flow field direction, indicating that the in-plane channels
increase the utilization of the CL under the rib area. An oxygen-transport
resistance analysis shows that both molecular and Knudsen diffusion can be
facilitated with the introduction of the in-plane channels. The direct CL
patterning technique provides a platform for the fabrication of advanced CL
structures with a high structural fidelity and design flexibility and a rational
guideline for designing high-performance CLs.
PMID- 29341583
TI - Tumor Catalytic-Photothermal Therapy with Yolk-Shell Gold@Carbon Nanozymes.
AB - Nanozymes, as a new generation of artificial enzymes, offer great opportunities
in biomedical engineering and disease treatment. Synergizing the multiple
intrinsic functions of nanozymes can improve their performance in biological
systems. Here, we report a novel nanozyme with yolk-shell structure fabricated by
combining a single gold nanoparticle core with a porous hollow carbon shell
nanospheres (Au@HCNs). Au@HCNs exhibited enzyme-like activities similar to
horseradish peroxidase and oxidase under an acidic environment, showing the
ability of ROS generation. More importantly, the ROS production of Au@HCNs was
significantly improved upon 808 nm light irradiation by the photothermal effect,
which is often used for tumor therapy. Cellular and animal studies further
demonstrated that the efficient tumor destruction was achieved through the
combination of light-enhanced ROS and photothermal therapy. These results implied
that the intrinsic enzyme-like activity and photothermal conversion of nanozymes
can be synergized for efficient tumor treatment, providing a proof-of-concept of
tumor catalytic-photothermal therapy based on nanozymes.
PMID- 29341584
TI - Preparation of a Smart and Portable Film for in Situ Sensing of Iron
Microcorrosion.
AB - Corrosion of iron-containing materials, which presents serious economic and
safety problems, normally begins with microcorrosion, which refers to the early
stages of corrosion before visible changes appear on the surface. If
microcorrosion could be detected and repaired immediately, corrosion damage could
be greatly reduced. Current technology and materials, however, are not able to
detect microcorrosion of iron in a cheap and convenient manner. Here, we have
used a natural product, ellagic acid (EA), to fabricate an EA-functionalized
poly(vinyl alcohol) (PVA) film (EAF) for in situ sensing of the initial stage of
microcorrosion. EAF was able to effectively sense iron microcorrosion via an
obvious color change. The film also had good long-term stability and mechanical
strength. Since EAF can be easily prepared from inexpensive and green raw
materials, the film opens up a new opportunity for the detection of iron
microcorrosion.
PMID- 29341585
TI - Self-Powered Microfluidic Transport System Based on Triboelectric Nanogenerator
and Electrowetting Technique.
AB - Electrowetting technique is an actuation method for manipulating position and
velocity of fluids in the microchannels. By combining electrowetting technique
and a freestanding mode triboelectric nanogenerator (TENG), we have designed a
self-powered microfluidic transport system. In this system, a mini vehicle is
fabricated by using four droplets to carry a pallet (6 mm * 8 mm), and it can
transport some tiny object on the track electrodes under the drive of TENG. The
motion of TENG can provide both driving power and control signal for the mini
vehicle. The maximum load for this mini vehicle is 500 mg, and its highest
controllable velocity can reach 1 m/s. Freestanding TENG has shown excellent
capability to manipulate microfluid. Under the drive of TENG, the minimum volume
of the droplet can reach 70-80 nL, while the tiny droplet can freely move on both
horizontal and vertical planes. Finally, another strategy for delivering
nanoparticles to the designated position has also been demonstrated. This
proposed self-powered transport technique may have great applications in the
field of microsolid/liquid manipulators, drug delivery systems, microrobotics,
and human-machine interactions.
PMID- 29341586
TI - Development of a Cytopathic Effect-Based Phenotypic Screening Assay against
Cryptosporidium.
AB - Cryptosporidiosis is a diarrheal disease predominantly caused by Cryptosporidium
parvum ( Cp) and Cryptosporidium hominis ( Ch), apicomplexan parasites which
infect the intestinal epithelial cells of their human hosts. The only approved
drug for cryptosporidiosis is nitazoxanide, which shows limited efficacy in
immunocompromised children, the most vulnerable patient population. Thus, new
therapeutics and in vitro infection models are urgently needed to address the
current unmet medical need. Toward this aim, we have developed novel cytopathic
effect (CPE)-based Cp and Ch assays in human colonic tumor (HCT-8) cells and
compared them to traditional imaging formats. Further model validation was
achieved through screening a collection of FDA-approved drugs and confirming many
previously known anti- Cryptosporidium hits as well as identifying a few novel
candidates. Collectively, our data reveals this model to be a simple, functional,
and homogeneous gain of signal format amenable to high throughput screening,
opening new avenues for the discovery of novel anticryptosporidials.
PMID- 29341587
TI - Fucoidan Prolongs the Circulation Time of Dextran-Coated Iron Oxide
Nanoparticles.
AB - The magnetic properties and safety of dextran-coated superparamagnetic iron oxide
nanoparticles (SPIONs) have facilitated their clinical use as MRI contrast agents
and stimulated research on applications for SPIONs in particle imaging and
magnetic hyperthermia. The wider clinical potential of SPIONs, however, has been
limited by their rapid removal from circulation via the reticuloendothelial
system (RES). We explored the possibility of extending SPION circulatory time
using fucoidan, a seaweed-derived food supplement, to inhibit RES uptake. The
effects of fucoidan on SPION biodistribution were evaluated using ferucarbotran,
which in its pharmaceutical formulation (Resovist) targets the RES. Ferucarbotran
was radiolabeled at the iron oxide core with technetium-99m (99mTc; t1/2 = 6 h)
or zirconium-89 (89Zr; t1/2 = 3.3 days). Results obtained with 99mTc
ferucarbotran demonstrated that administration of fucoidan led to a 4-fold
increase in the circulatory half-life (t1/2 slow) from 37.4 to 150 min (n = 4; P
< 0.0001). To investigate whether a longer circulatory half-life could lead to
concomitant increased tumor uptake, the effects of fucoidan were tested with 89Zr
ferucarbotran in mice bearing syngeneic subcutaneous (GL261) tumors. In this
model, the longer circulatory half-life achieved with fucoidan was associated
with a doubling in tumor SPION uptake (n = 5; P < 0.001). Fucoidan was also
effective in significantly increasing the circulatory half-life of perimag-COOH,
a commercially available SPION with a larger hydrodynamic size (130 nm) than
ferucarbotran (65 nm). These findings indicate successful diversion of SPIONs
away from the hepatic RES and show realistic potential for future clinical
applications.
PMID- 29341588
TI - Human Neuraminidase Isoenzymes Show Variable Activities for 9- O-Acetyl-sialoside
Substrates.
AB - Recognition of terminal sialic acids is central to many cellular processes, and
structural modification of sialic acid can disrupt these interactions. A
prominent, naturally occurring, modification of sialic acid is 9- O-acetylation
(9- O-Ac). Study of this modification through generation and analysis of 9- O-Ac
sialosides is challenging because of the lability of the acetate group.
Fundamental questions regarding the role of 9- O-Ac sialic acids remain
unanswered, including what effect it may have on recognition and hydrolysis by
the human neuraminidase enzymes (hNEU). To investigate the substrate activity of
9- O-acetylated sialic acids (Neu5,9Ac2), we synthesized an acetylated
fluorogenic hNEU substrate 2'-(4-methylumbelliferyl)-9- O-acetyl-alpha-d- N
acetylneuraminic acid. Additionally, we generated a panel of octyl
sialyllactosides containing modified sialic acids including variation in linkage,
9- O-acetylation, and C-5 group (Neu5Gc). Relative rates of substrate cleavage by
hNEU were determined using fluorescence spectroscopy and electrospray ionization
mass spectrometry. We report that 9- O-acetylation had a significant, and
differential, impact on sialic acid hydrolysis by hNEU with general substrate
tolerance following the trend of Neu5Ac > Neu5Gc ? Neu5,9Ac2 for NEU2, NEU3, and
NEU4. Both NEU2 and NEU3 had remarkably reduced activity for Neu5,9Ac2 containing
substrates. Other isoenzymes appeared to be more tolerant, with NEU4 even showing
increased activity on Neu5,9Ac2 substrates with an aryl aglycone. The impact of
these minor structural changes to sialic acid on hNEU activity was unexpected,
and these results provide evidence of the substantial influence of 9- O-Ac
modifications on hNEU enzyme substrate specificity. Furthermore, these findings
may implicate hNEU in processes governed by 9- O-acetyltransferases and
esterases.
PMID- 29341589
TI - Metal-Organic Frameworks-Derived Hierarchical Co3O4 Structures as Efficient
Sensing Materials for Acetone Detection.
AB - Highly sensitive and stable gas sensors have attracted much attention because
they are the key to innovations in the fields of environment, health, energy
savings and security, etc. Sensing materials, which influence the practical
sensing performance, are the crucial parts for gas sensors. Metal-organic
frameworks (MOFs) are considered as alluring sensing materials for gas sensors
because of the possession of high specific surface area, unique morphology,
abundant metal sites, and functional linkers. Herein, four kinds of porous
hierarchical Co3O4 structures have been selectively controlled by optimizing the
thermal decomposition (temperature, rate, and atmosphere) using ZIF-67 as
precursor that was obtained from coprecipitation method with the co-assistance of
cobalt salt and 2-methylimidazole in the solution of methanol. These hierarchical
Co3O4 structures, with controllable cross-linked channels, meso-/micropores, and
adjustable surface area, are efficient catalytic materials for gas sensing.
Benefits from structural advantages, core-shell, and porous core-shell Co3O4
exhibit enhanced sensing performance compared to those of porous popcorn and
nanoparticle Co3O4 to acetone gas. These novel MOF-templated Co3O4 hierarchical
structures are so fantastic that they can be expected to be efficient sensing
materials for development of low-temperature operating gas sensors.
PMID- 29341590
TI - Correction to Fourier Transform Infrared Studies on the Dissociation Behavior of
Metal-Chelating Polyelectrolyte Brushes.
PMID- 29341591
TI - The Development of Benzimidazole-Based Clickable Probes for the Efficient
Labeling of Cellular Protein Arginine Deiminases (PADs).
AB - Citrullination is the post-translational hydrolysis of peptidyl-arginines to form
peptidyl-citrulline, a reaction that is catalyzed by the protein arginine
deiminases (PADs), a family of calcium-regulated enzymes. Aberrantly increased
protein citrullination is associated with a slew of autoimmune diseases (e.g.,
rheumatoid arthritis (RA), multiple sclerosis, lupus, and ulcerative colitis) and
certain cancers. Given the clear link between increased PAD activity and human
disease, the PADs are therapeutically relevant targets. Herein, we report the
development of next generation cell permeable and "clickable" probes (BB-Cl-Yne
and BB-F-Yne) for covalent labeling of the PADs both in vitro and in cell-based
systems. Using advanced chemoproteomic technologies, we also report the off
targets of both BB-Cl-Yne and BB-F-Yne. The probes are highly specific for the
PADs, with relatively few off targets, especially BB-F-Yne, suggesting the
preferential use of the fluoroacetamidine warhead in next generation irreversible
PAD inhibitors. Notably, these compounds can be used in a variety of modalities,
including the identification of off targets of the parent compounds and as
activity-based protein profiling probes in target engagement assays to
demonstrate the efficacy of PAD inhibitors.
PMID- 29341592
TI - Application of Decafluorobiphenyl (DFBP) Moiety as a Linker in Bioconjugation.
AB - Considerable attention has been devoted to fluorinated compounds due to their
unique and interesting properties. Many modern pharmaceuticals contain
fluorinated substituents, which are commonly synthesized using selective
fluorinating reagents. Decafluorobiphenyl (DFBP) as a fluorinated linker is
susceptible to nucleophilic attack. This nucleophilic reaction has been widely
studied using various nucleophiles. Sulfur and nitrogen containing nucleophiles
have been of particular interest, especially in bioconjugated reactions. This
review focuses on the SNAr reactivity of DFBP in formation of C-X (X = S, N)
bonds, to be applied in bioconjugation in organic chemistry. The review aims to
highlight the crucial factors that govern the chemistry behind the activation of
F-CAr-CAr-F bonds as a linker in the synthesis of novel peptides, proteins, and
biologics.
PMID- 29341593
TI - Analysis of Cellular Tyrosine Phosphorylation via Chemical Rescue of
Conditionally Active Abl Kinase.
AB - Identifying direct substrates targeted by protein kinases is important in
understanding cellular physiology and intracellular signal transduction. Mass
spectrometry-based quantitative proteomics provides a powerful tool for
comprehensively characterizing the downstream substrates of protein kinases. This
approach is efficiently applied to receptor kinases that can be precisely,
directly, and rapidly activated by some agent, such as a growth factor. However,
nonreceptor tyrosine kinase Abl lacks the experimental advantage of extracellular
growth factors as immediate and direct stimuli. To circumvent this limitation, we
combine a chemical rescue approach with quantitative phosphoproteomics to
identify targets of Abl and their phosphorylation sites with enhanced temporal
resolution. Both known and novel putative substrates are identified, presenting
opportunities for studying unanticipated functions of Abl under physiological and
pathological conditions.
PMID- 29341595
TI - Self-Healing Hydrogels of Low Molecular Weight Poly(vinyl alcohol) Assembled by
Host-Guest Recognition.
AB - Poly(vinyl alcohol) (PVA) is a cytocompatible synthetic polymer and has been
commonly used to prepare hydrogels. Bile acids and beta-cyclodextrin are both
natural compounds and they form stable host-guest inclusion complexes. They are
attached covalently onto a low molecular weight PVA separately. Self-healing
hydrogels can be easily formed by mixing the aqueous solutions of these PVA based
polymers. The mechanical properties of the hydrogels can be tuned by varying the
molar fractions of bile acid units on PVA. The dynamic inclusion complexation of
the host-guest pair of the hydrogel allows the self-healing rapidly under ambient
atmosphere and their mechanical properties could recover their original values in
1 min after incision. These PVA based polymers exhibited the good
cytocompatibility and high hemocompatibility as shown by their biological
evaluations. The use of natural compounds for host-guest interaction make such
gels especially convenient to use as biomaterials, an advantage over conventional
hydrogels prepared through freeze-thaw method.
PMID- 29341596
TI - Core-Shell ZIF-8@ZIF-67-Derived CoP Nanoparticle-Embedded N-Doped Carbon Nanotube
Hollow Polyhedron for Efficient Overall Water Splitting.
AB - The construction of highly active and stable non-noble-metal electrocatalysts for
hydrogen and oxygen evolution reactions is a major challenge for overall water
splitting. Herein, we report a novel hybrid nanostructure with CoP nanoparticles
(NPs) embedded in a N-doped carbon nanotube hollow polyhedron (NCNHP) through a
pyrolysis-oxidation-phosphidation strategy derived from core-shell ZIF-8@ZIF-67.
Benefiting from the synergistic effects between highly active CoP NPs and NCNHP,
the CoP/NCNHP hybrid exhibited outstanding bifunctional electrocatalytic
performances. When the CoP/NCNHP was employed as both the anode and cathode for
overall water splitting, a potential as low as 1.64 V was needed to achieve the
current density of 10 mA.cm-2, and it still exhibited superior activity after
continuously working for 36 h with nearly negligible decay in potential. Density
functional theory calculations indicated that the electron transfer from NCNHP to
CoP could increase the electronic states of the Co d-orbital around the Fermi
level, which could increase the binding strength with H and therefore improve the
electrocatalytic performance. The strong stability is attributed to high
oxidation resistance of the CoP surface protected by the NCNHP.
PMID- 29341594
TI - Designing Flavoprotein-GFP Fusion Probes for Analyte-Specific Ratiometric
Fluorescence Imaging.
AB - The development of genetically encoded fluorescent probes for analyte-specific
imaging has revolutionized our understanding of intracellular processes. Current
classes of intracellular probes depend on the selection of binding domains that
either undergo conformational changes on analyte binding or can be linked to
thiol redox chemistry. Here we have designed novel probes by fusing a
flavoenzyme, whose fluorescence is quenched on reduction by the analyte of
interest, with a GFP domain to allow for rapid and specific ratiometric sensing.
Two flavoproteins, Escherichia coli thioredoxin reductase and Saccharomyces
cerevisiae lipoamide dehydrogenase, were successfully developed into thioredoxin
and NAD+/NADH specific probes, respectively, and their performance was evaluated
in vitro and in vivo. A flow cell format, which allowed dynamic measurements, was
utilized in both bacterial and mammalian systems. In E. coli the first reported
intracellular steady-state of the cytoplasmic thioredoxin pool was measured. In
HEK293T mammalian cells, the steady-state cytosolic ratio of NAD+/NADH induced by
glucose was determined. These genetically encoded fluorescent constructs
represent a modular approach to intracellular probe design that should extend the
range of metabolites that can be quantitated in live cells.
PMID- 29341597
TI - The WYL Domain of the PIF1 Helicase from the Thermophilic Bacterium Thermotoga
elfii is an Accessory Single-Stranded DNA Binding Module.
AB - PIF1 family helicases are conserved from bacteria to man. With the exception of
the well-studied yeast PIF1 helicases (e.g., ScPif1 and ScRrm3), however, very
little is known about how these enzymes help maintain genome stability. Indeed,
we lack a basic understanding of the protein domains found N- and C-terminal to
the characteristic central PIF1 helicase domain in these proteins. Here, using
chimeric constructs, we show that the ScPif1 and ScRrm3 helicase domains are
interchangeable and that the N-terminus of ScRrm3 is important for its function
in vivo. This suggests that PIF1 family helicases evolved functional modules
fused to a generic motor domain. To investigate this hypothesis, we characterized
the biochemical activities of the PIF1 helicase from the thermophilic bacterium
Thermotoga elfii (TePif1), which contains a C-terminal WYL domain of unknown
function. Like helicases from other thermophiles, recombinant TePif1 was easily
prepared, thermostable in vitro, and displayed activities similar to its
eukaryotic homologues. We also found that the WYL domain was necessary for high
affinity single-stranded DNA (ssDNA) binding and affected both ATPase and
helicase activities. Deleting the WYL domain from TePif1 or mutating conserved
residues in the predicted ssDNA binding site uncoupled ATPase activity and DNA
unwinding, leading to higher rates of ATP hydrolysis but less efficient DNA
helicase activity. Our findings suggest that the domains of unknown function
found in eukaryotic PIF1 helicases may also confer functional specificity and
additional activities to these enzymes, which should be investigated in future
work.
PMID- 29341598
TI - A Joint Strategy To Evaluate the Microscopic Origin of the Second-Harmonic
Generation Response in Nonpolar ABCO3F Compounds.
AB - In this paper, a joint strategy was proposed to investigate the microscopic
origin of the second-harmonic-generation (SHG) response in nonpolar ABCO3F
compounds. The SHG coefficients of ABCO3F were evaluated using finite-field and
sum-over-states methods. The tendency of the obtained SHG tensors is in good
agreement with the powder SHG response. The atomic contribution was investigated
using variation of the atomic charges and bandwidth of occupied atomic states.
The results show that oxygen states play a key role in determining the SHG
response, and the neighboring divalent cations exert a indirect influence via
covalent interaction. The bidentate bonding pattern is beneficial to obtaining a
largely enhanced SHG response.
PMID- 29341599
TI - Ni-Catalyzed Carbon-Carbon Bond-Forming Reductive Amination.
AB - This report describes a three-component, Ni-catalyzed reductive coupling that
enables the convergent synthesis of tertiary benzhydryl amines, which are
challenging to access by traditional reductive amination methodologies. The
reaction makes use of iminium ions generated in situ from the condensation of
secondary N-trimethylsilyl amines with benzaldehydes, and these species undergo
reaction with several distinct classes of organic electrophiles. The synthetic
value of this process is demonstrated by a single-step synthesis of antimigraine
drug flunarizine (Sibelium) and high yielding derivatization of paroxetine
(Paxil) and metoprolol (Lopressor). Mechanistic investigations support a
sequential oxidative addition mechanism rather than a pathway proceeding via
alpha-amino radical formation. Accordingly, application of catalytic conditions
to an intramolecular reductive coupling is demonstrated for the synthesis of endo
and exocyclic benzhydryl amines.
PMID- 29341600
TI - Combination of Heparin Binding Peptide and Heparin Cell Surface Coatings for
Mesenchymal Stem Cell Spheroid Assembly.
AB - Microtissues containing multiple cell types have been used in both in vitro
models and in vivo tissue repair applications. However, to improve throughput,
there is a need to develop a platform that supports self-assembly of a large
number of 3D microtissues containing multiple cell types in a dynamic suspension
system. Thus, the objective of this study was to exploit the binding interaction
between the negatively charged glycosaminoglycan, heparin, and a known heparin
binding peptide to establish a method that promotes assembly of mesenchymal stem
cell (MSC) spheroids into larger aggregates. We characterized heparin binding
peptide (HEPpep) and heparin coatings on cell surfaces and determined the
specificity of these coatings in promoting assembly of MSC spheroids in dynamic
culture. Overall, combining spheroids with both coatings promoted up to 70 +/-
11% of spheroids to assemble into multiaggregate structures, as compared to only
10 +/- 4% assembly when cells having the heparin coating were cultured with cells
coated with a scrambled peptide. These results suggest that this self-assembly
method represents an exciting approach that may be applicable for a wide range of
applications in which cell aggregation is desired.
PMID- 29341601
TI - Determining Double Bond Position in Lipids Using Online Ozonolysis Coupled to
Liquid Chromatography and Ion Mobility-Mass Spectrometry.
AB - The increasing focus on lipid metabolism has revealed a need for analytical
techniques capable of structurally characterizing lipids with a high degree of
specificity. Lipids can exist as any one of a large number of double bond
positional isomers, which are indistinguishable by single-stage mass spectrometry
alone. Ozonolysis reactions coupled to mass spectrometry have previously been
demonstrated as a means for localizing double bonds in unsaturated lipids. Here
we describe an online, solution-phase reactor using ozone produced via a low
pressure mercury lamp, which generates aldehyde products diagnostic of cleavage
at a particular double bond position. This flow-cell device is utilized in
conjunction with structurally selective ion mobility-mass spectrometry. The lamp
mediated reaction was found to be effective for multiple lipid species in both
positive and negative ionization modes, and the conversion efficiency from
precursor to product ions was tunable across a wide range (20-95%) by varying the
flow rate through the ozonolysis device. Ion mobility separation of the
ozonolysis products generated additional structural information and revealed the
presence of saturated species in a complex mixture. The method presented here is
simple, robust, and readily coupled to existing instrument platforms with minimal
modifications necessary. For these reasons, application to standard lipidomic
workflows is possible and aids in more comprehensive structural characterization
of a myriad of lipid species.
PMID- 29341602
TI - Polybrominated Diphenyl Ethers, Polychlorinated Biphenyls, and 2,2-Bis(4
chlorophenyl)-1,1-dichloroethene in 7- and 9-Year-Old Children and Their Mothers
in the Center for the Health Assessment of Mothers and Children of Salinas
Cohort.
AB - We report longitudinal serum concentrations of select persistent organic
pollutants (POPs) in children at ages 7 and 9 years and in their mothers
prenatally and again when the children were 9 years old. The participating
families were enrolled in the Center for the Health Assessment of Mothers and
Children of Salinas (CHAMACOS), a longitudinal birth cohort study of low-income
Hispanic families residing in the Salinas Valley, California. We observed
decreasing concentrations in the mothers with year of serum collection (2009 vs
2011) for six out of seven polybrominated diphenyl ether (PBDE) congeners and for
2,2',4,4',5-pentachlorobiphenyl (CB-99; p < 0.05). The 9-year-old children had
similarly decreasing serum concentrations of all seven PBDE congeners, CB-99, and
2,2',3,4,4',5'- and 2,3,3',4,4',6-hexachlorobiphenyl (CB-138/158) with year of
serum collection (2009 vs 2011; p < 0.05). In mixed effect models accounting for
weight gain as the children aged from 7 to 9 years, we observed an annual
decrease (-8.3% to -13.4%) in tri- to hexaBDE concentrations (p < 0.001), except
for 2,2',3,4,4'-tetrabromodiphenyl ether (BDE-85) and 2,2',4,4',5,5'
hexabromodiphenyl ether (BDE-153). The concentrations of these congeners were not
associated with time of serum collection and instead showed an -0.9% to -2.6%
decrease per kilogram of weight gain during the study period (p < 0.05). In the
case of tetra- to heptachlorobiphenyls, we observed -0.5% to -0.7% decrease in
serum concentration per kilogram of weight gain (p < 0.05) and -3.0% to -3.7%
decrease in serum concentration per year of aging (p < 0.05), except for
2,3',4,4',5-pentachlorobiphenyl (CB-118) and 2,2',4,4',5,5'-hexachlorobiphenyl
(CB-153), which were not associated with time of serum draw. 2,2-Bis(4
chlorophenyl)-1,1-dichloroethene (p,p'-DDE) decreased -2.4%/kg of weight gain
between the two sampling points (p < 0.001). These findings suggest that as
children grow, dilution in a larger body size plays an important role in
explaining reductions in body burden in the case of traditional POPs such as PCBs
and p,p'-DDE. By contrast, in the case of PBDEs, reductions are likely explained
by reduction in exposure, as illustrated by decreased concentrations in more
recent years, possibly amplified by presumed shorter biological half-life than
other POPs.
PMID- 29341603
TI - PokMT1 from the Polyketomycin Biosynthetic Machinery of Streptomyces
diastatochromogenes Tu6028 Belongs to the Emerging Family of C-Methyltransferases
That Act on CoA-Activated Aromatic Substrates.
AB - Recent biochemical characterizations of the MdpB2 CoA ligase and MdpB1 C
methyltransferase (C-MT) from the maduropeptin (MDP, 2) biosynthetic machinery
revealed unusual pathway logic involving C-methylation occurring on a CoA
activated aromatic substrate. Here we confirmed this pathway logic for the
biosynthesis of polyketomycin (POK, 3). Biochemical characterization
unambiguously established that PokM3 and PokMT1 catalyze the sequential
conversion of 6-methylsalicylic acid (6-MSA, 4) to form 3,6-dimethylsalicylyl-CoA
(3,6-DMSA-CoA, 6), which serves as the direct precursor for the 3,6
dimethylsalicylic acid (3,6-DMSA) moiety in the biosynthesis of 3. PokMT1
catalyzes the C-methylation of 6-methylsalicylyl-CoA (6-MSA-CoA, 5) with a kcat
of 1.9 min-1 and a Km of 2.2 +/- 0.1 MUM, representing the most proficient C-MT
characterized to date. Bioinformatics analysis of MTs from natural product
biosynthetic machineries demonstrated that PokMT1 and MdpB1 belong to a
phylogenetic clade of C-MTs that preferably act on aromatic acids. Significantly,
this clade includes the structurally characterized enzyme SibL, which catalyzes C
methylation of 3-hydroxykynurenine in its free acid form, using two conserved
tyrosine residues for catalysis. A homology model and site-directed mutagenesis
suggested that PokMT1 also employs this unusual arrangement of tyrosine residues
to coordinate C-methylation but revealed a large cavity capable of accommodating
the CoA moiety tethered to 5. CoA activation of the aromatic acid substrate may
represent a general strategy that could be exploited to improve catalytic
efficiency. This study sets the stage to further investigate and exploit the
catalytic utility of this emerging family of C-MTs in biocatalysis and synthetic
biology.
PMID- 29341604
TI - Ce3+-Doping to Modulate Photoluminescence Kinetics for Efficient CsPbBr3
Nanocrystals Based Light-Emitting Diodes.
AB - Inorganic perovskite CsPbBr3 nanocrystals (NCs) are emerging, highly attractive
light emitters with high color purity and good thermal stability for light
emitting diodes (LEDs). Their high photo/electroluminescence efficiencies are
very important for fabricating efficient LEDs. Here, we propose a novel strategy
to enhance the photo/electroluminescence efficiency of CsPbBr3 NCs through doping
of heterovalent Ce3+ ions via a facile hot-injection method. The Ce3+ cation was
chosen as the dopant for CsPbBr3 NCs by virtue of its similar ion radius and
formation of higher energy level of conduction band with bromine in comparison
with the Pb2+ cation to maintain the integrity of perovskite structure without
introducing additional trap states. It was found that by increasing the doping
amount of Ce3+ in CsPbBr3 NCs to 2.88% (atomic percentage of Ce compared to Pb)
the photoluminescence quantum yield (PLQY) of CsPbBr3 NCs reached up to 89%, a
factor of 2 increase in comparison with the native, undoped ones. The ultrafast
transient absorption and time-resolved photoluminescence (PL) spectroscopy
revealed that Ce3+-doping can significantly modulate the PL kinetics to enhance
the PL efficiency of doped CsPbBr3 NCs. As a result, the LED device fabricated by
adopting Ce3+-doped CsPbBr3 NCs as the emitting layers exhibited a pronounced
improvement of electroluminescence with external quantum efficiency (EQE) from
1.6 to 4.4% via Ce3+-doping.
PMID- 29341605
TI - Prediction of Active Site and Distal Residues in E. coli DNA Polymerase III alpha
Polymerase Activity.
AB - The process of DNA replication is carried out with high efficiency and accuracy
by DNA polymerases. The replicative polymerase in E. coli is DNA Pol III, which
is a complex of 10 different subunits that coordinates simultaneous replication
on the leading and lagging strands. The 1160-residue Pol III alpha subunit is
responsible for the polymerase activity and copies DNA accurately, making one
error per 105 nucleotide incorporations. The goal of this research is to
determine the residues that contribute to the activity of the polymerase subunit.
Homology modeling and the computational methods of THEMATICS and POOL were used
to predict functionally important amino acid residues through their computed
chemical properties. Site-directed mutagenesis and biochemical assays were used
to validate these predictions. Primer extension, steady-state single-nucleotide
incorporation kinetics, and thermal denaturation assays were performed to
understand the contribution of these residues to the function of the polymerase.
This work shows that the top 15 residues predicted by POOL, a set that includes
the three previously known catalytic aspartate residues, seven remote residues,
plus five previously unexplored first-layer residues, are important for function.
Six previously unidentified residues, R362, D405, K553, Y686, E688, and H760, are
each essential to Pol III activity; three additional residues, Y340, R390, and
K758, play important roles in activity.
PMID- 29341606
TI - Human Oxoguanine Glycosylase 1 Removes Solution Accessible 8-Oxo-7,8
dihydroguanine Lesions from Globally Substituted Nucleosomes Except in the Dyad
Region.
AB - Persistent DNA damage is responsible for mutagenesis, aging, and disease. Repair
of the prototypic oxidatively damaged guanine lesion 8-oxo-7,8-dihydroguanine (8
oxoG) is initiated by oxoguanine glycosylase (hOGG1 in humans). In this work, we
examine hOGG1 activity on DNA packaged as it is in chromatin, in a nucleosome
core particle (NCP). We use synthetic methods to generate a population of NCPs
with G to 8-oxoG substitutions and evaluate the global profile of hOGG1 repair in
packaged DNA. For several turns of the helix, we observe that solution accessible
8-oxoGs are sites of activity for hOGG1. At the dyad axis, however, hOGG1
activity is suppressed, even at lesions predicted to be solution accessible by
hydroxyl radical footprinting (HRF). We predict this diminished activity is due
to the properties of the DNA unique to the dyad axis and/or the local histone
environment. In contrast to the dyad axis, the DNA ends reveal hOGG1 activity at
sites predicted by HRF to be both solution accessible and inaccessible. We
attribute the lack of correlation between hOGG1 activity and solution
accessibility at the ends of the DNA to transient unwrapping of the DNA from the
protein core, thus exposing the inward-facing lesions.
PMID- 29341607
TI - In Vitro Pharmacokinetic Optimizations of AM2-S31N Channel Blockers Led to the
Discovery of Slow-Binding Inhibitors with Potent Antiviral Activity against Drug
Resistant Influenza A Viruses.
AB - Influenza viruses are respiratory pathogens that are responsible for both
seasonal influenza epidemics and occasional influenza pandemics. The narrow
therapeutic window of oseltamivir, coupled with the emergence of drug resistance,
calls for the next-generation of antivirals. With our continuous interest in
developing AM2-S31N inhibitors as oral influenza antivirals, we report here the
progress of optimizing the in vitro pharmacokinetic (PK) properties of AM2-S31N
inhibitors. Several AM2-S31N inhibitors, including compound 10b, were discovered
to have potent channel blockage, single to submicromolar antiviral activity, and
favorable in vitro PK properties. The antiviral efficacy of compound 10b was also
synergistic with oseltamivir carboxylate. Interestingly, binding kinetic studies
(Kd, Kon, and Koff) revealed several AM2-S31N inhibitors that have similar Kd
values but significantly different Kon and Koff values. Overall, this study
identified a potent lead compound (10b) with improved in vitro PK properties that
is suitable for the in vivo mouse model studies.
PMID- 29341608
TI - Molecular Dynamics Pinpoint the Global Fluorine Effect in Balanoid Binding to
PKCepsilon and PKA.
AB - (-)-Balanol is an adenosine triphosphate mimic that inhibits protein kinase C
(PKC) isozymes and cAMP-dependent protein kinase (PKA) with limited selectivity.
While PKA is known as a tumor promoter, PKC isozymes can be tumor promoters or
suppressors. In particular, PKCepsilon is frequently involved in tumorigenesis
and a potential target for anticancer drugs. We recently reported that
stereospecific fluorination of balanol yielded a balanoid with enhanced
selectivity for PKCepsilon over other PKC isozymes and PKA, although the global
fluorine effect behind the selectivity enhancement is not fully understood.
Interestingly, in contrast to PKA, PKCepsilon is more sensitive to this fluorine
effect. Here we investigate the global fluorine effect on the different binding
responses of PKCepsilon and PKA to balanoids using molecular dynamics (MD)
simulations. For the first time to the best of our knowledge, we found that a
structurally equivalent residue in each kinase, Thr184 in PKA and Ala549 in
PKCepsilon, is essential for the different binding responses. Furthermore, the
study revealed that the invariant Lys, Lys73 in PKA and Lys437 in PKCepsilon,
already known to have a crucial role in the catalytic activity of kinases, serves
as the main anchor for balanol binding. Overall, while Thr184 in PKA attenuates
the effect of fluorination, Ala549 permits remote response of PKCepsilon to
fluorine substitution, with implications for rational design of future balanol
based PKCepsilon inhibitors.
PMID- 29341609
TI - Probing and Quantifying the Food-Borne Pathogens and Toxins: From In Vitro to In
Vivo.
AB - Development of real-time and in situ analytical methods for determination of food
borne pathogens and toxins ingested into the human body would be a promising
research direction in the food-safety area. The present perspective starts with
summarization of the up-to-date progress of the nanomaterial-assisted in vitro
detection methods for pathogens and toxins and finally focuses on application of
animal bioimaging to in vivo study, including prospective strategies for in vivo
quantification of target pathogens or toxins and in vivo investigation of their
behaviors inside the living body, with the assistance of real-time and non
invasive optical bioimaging. This perspective provides the advisory direction for
food-safety research, from in vitro to in vivo, along with a prospective
discussion of the further development roadmap of the food-safety detection
techniques, especially the bioimaging-guided methods for investigation and
mediation of the food contamination effect to human health.
PMID- 29341610
TI - Visible-Light-Mediated Ipso-Carboacylation of Alkynes: Synthesis of 3
Acylspiro[4,5]trienones from N-(p-Methoxyaryl)propiolamides and Acyl Chlorides.
AB - A novel visible-light-mediated ipso-carboacylation of N-(p
methoxyaryl)propiolamides with acyl chloride has been established for the
synthesis of diverse 3-acylspiro[4,5]trienones with high selectivity and
efficiency. This method represents a new difunctionalization of alkynes through
cross coupling of the acyl chloride C-Cl bonds with an ipso-aromatic carbon by
simultaneously forming two new carbon-carbon bonds and one carbon-oxygen double
bond.
PMID- 29341611
TI - Moving Boundary Truncated Grid Method for Wave Packet Dynamics.
AB - The moving boundary truncated grid method is developed to significantly reduce
the number of grid points required for wave packet propagation. The time
dependent Schrodinger equation (TDSE) and the imaginary time Schrodinger equation
(ITSE) are integrated using an adaptive algorithm which economizes the number of
grid points. This method employs a variable number of grid points in the Eulerian
frame (grid points fixed in space) and adaptively defines the boundaries of the
truncated grid. The truncated grid method is first applied to the time
integration of the TDSE for the photodissociation dynamics of NOCl and a three
dimensional quantum barrier scattering problem. The time-dependent truncated grid
precisely captures the wave packet evolution for the photodissociation of NOCl
and finely adjusts according to the process of the wave packet bifurcation into
reflected and transmitted components for the barrier scattering problem. The
truncated grid method is also applied to the time integration of the ITSE for the
eigenstates of quantum systems. Compared to the full grid calculations, the
truncated grid method requires fewer grid points to achieve high accuracy for the
stationary state energies and wave functions for a two-dimensional double well
potential and the Ar trimer. Therefore, the truncated grid method demonstrates a
significant reduction in the number of grid points needed to perform accurate
wave packet propagation governed by the TDSE or the ITSE.
PMID- 29341612
TI - Stabilization of NaBH4 in Methanol Using a Catalytic Amount of NaOMe. Reduction
of Esters and Lactones at Room Temperature without Solvent-Induced Loss of
Hydride.
AB - Rapid reaction of NaBH4 with MeOH precludes its use as a solvent for large-scale
ester reductions. We have now learned that a catalytic amount of NaOMe (5 mol %)
stabilizes NaBH4 solutions in methanol at 25 degrees C and permits the use of
these solutions for the reduction of esters to alcohols. The generality of this
reduction method was demonstrated using 22 esters including esters of naturally
occurring chiral gamma-butyrolactone containing dicarboxylic acids. This method
permits the chemoselective reductions of esters in the presence of cyano and
nitro groups and the reductive cyclization of a pyrrolidinedione ester to a fused
five-membered furo[2,3-b]pyrrole and a (-)-crispine A analogue in high optical
and chemical yields. Lactones, aliphatic esters, aromatic esters containing
electron-withdrawing groups, and heteroaryl esters are reduced more rapidly than
aryl esters containing electron-donating groups. The 11B NMR spectrum of the
NaOMe-stabilized NaBH4 solutions showed a minor quartet due to
monomethoxyborohydride (NaBH3OMe) that persisted up to 18 h at 25 degrees C. We
postulate that NaBH3OMe is probably the active reducing agent. In support of this
hypothesis, the activation barrier for hydride transfer from BH3(OMe)- onto
benzoic acid methyl ester was calculated as 18.3 kcal/mol.
PMID- 29341613
TI - What Gives an Insulin Hexamer Its Unique Shape and Stability? Role of Ten
Confined Water Molecules.
AB - Self-assembly of proteins often gives rise to interesting quasi-stable structures
that serve important biological purposes. Insulin hexamer is such an assembly.
While monomer is the biologically active form of insulin, hexamer serves as the
storehouse of the hormone. The hexamer also prevents the formation of higher
order aggregates. While several studies explored the role of bivalent metal ions
like Zn2+, Ca2+, etc., in the stabilization of the hexameric form, the role of
water molecules has been ignored. We combine molecular dynamics simulations,
quantum calculations, and X-ray analyses to discover that a team of approximately
10 water molecules confined inside a barrel-shaped nanocavity at the center of
insulin hexamer is one of the major causes that account for the unusual stability
of the biomolecular assembly. These cavity water molecules exhibit interesting
dynamical features like intermittent escape and reentrance. We find that these
water molecules are dynamically slower than the bulk and weave an intricate
hydrogen bond network among themselves and with neighboring protein residues to
generate a robust backbone at the center of the hexamer that holds the
association strongly from inside and maintains the barrel shape.
PMID- 29341614
TI - Synthesis of Quinazolines via an Iron-Catalyzed Oxidative Amination of N-H
Ketimines.
AB - An efficient synthesis of quinazolines based on an iron-catalyzed C(sp3)-H
oxidation and intramolecular C-N bond formation using tert-BuOOH as the terminal
oxidant is described. The reaction of readily available 2-alkylamino
benzonitriles with various organometallic reagents led to 2-alkylamino N-H
ketimine species. The FeCl2-catalyzed C(sp3)-H oxidation of the alkyl group
employing tert-BuOOH followed by intramolecular C-N bond formation and
aromatization afforded a wide variety of 2,4-disubstituted quinazolines in good
to excellent yields.
PMID- 29341615
TI - Merely Measuring the UV-Visible Spectrum of Gold Nanoparticles Can Change Their
Charge State.
AB - Metallic nanostructures exhibit a strong plasmon resonance at a wavelength whose
value is sensitive to the charge density in the nanostructure, its size, shape,
interparticle coupling, and the dielectric properties of its surrounding medium.
Here we use UV-visible transmission and reflectance spectroscopy to track the
shifts of the plasmon resonance in an array of gold nanoparticles buried under
metal-oxide layers of varying thickness produced using atomic layer deposition
(ALD) and then coated with bulk layers of one of three metals: aluminum, silver,
or gold. A significant shift in the plasmon resonance was observed and a precise
value of omegap, the plasmon frequency of the gold comprising the nanoparticles,
was determined by modeling the composite of gold nanoparticles and metal-oxide
layer as an optically homogeneous film of core-shell particles bounded by two
substrates: one of quartz and the other being one of the aforementioned metals,
then using a Maxwell-Garnett effective medium expression to extract omegap for
the gold nanoparticles before and after coating with the bulk metals. Under
illumination, the change in the charge density of the gold nanoparticles per
particle determined from the change in the values of omegap is found to be some
50-fold greater than what traditional electrostatic contact electrification
models compute based on the work function difference of the two conductive
materials. Moreover, when using bulk gold as the capping layer, which should have
resulted in a negligible charge exchange between the gold nanoparticles and the
bulk gold, a significant charge transfer from the bulk gold layer to the
nanoparticles was observed as with the other metals. We explain these
observations in terms of the "plasmoelectric effect", recently described by
Atwater and co-workers, in which the gold nanoparticles modify their charge
density to allow their resonant wavelength to match that of the incident light,
thereby achieving, a lower value of the chemical potential due to the entropy
increase resulting from the conversion of the plasmon's energy to heat. We
conclude that even the act of registering the spectrum of nanoparticles is at
times sufficient to alter their charge densities and hence their UV-visible
spectra.
PMID- 29341616
TI - Stochasticity of Pores Interconnectivity in Li-O2 Batteries and its Impact on the
Variations in Electrochemical Performance.
AB - While large dispersions in electrochemical performance have been reported for
lithium oxygen batteries in the literature, they have not been investigated in
any depth. The variability in the results is often assumed to arise from
differences in cell design, electrode structure, handling and cell preparation at
different times. An accurate theoretical framework turns out to be needed to get
a better insight into the mechanisms underneath and to interpret experimental
results. Here, we develop and use a pore network model to simulate the
electrochemical performance of three-dimensionally resolved lithium-oxygen
cathode mesostructures obtained from TXM nanocomputed tomography. We apply this
model to the 3D reconstructed object of a Super P carbon electrode and calculate
discharge curves, using identical conditions, for four different zones in the
electrode and their reversed configurations. The resulting galvanostatic
discharge curves show some dispersion, (both in terms of capacity and
overpotential) which we attribute to the way pores are connected with each other.
Based on these results, we propose that the stochastic nature of pores
interconnectivity and the microscopic arrangement of pores can lead, at least
partially, to the variations in electrochemical results observed experimentally.
PMID- 29341618
TI - Reactions of 1,5-Diaryl-3-(trifluoromethyl)pent-1-en-4-yn-3-yl Cations with
Benzene in TfOH. Synthesis of CF3-"Helicopter"-Like Molecules.
AB - Trimethylsilyl ethers of 1,5-diaryl-3-(trifluoromethyl)pent-1-en-4-yn-3-oles in
superacid CF3SO3H (TfOH) give rise to the corresponding intermediate CF3
pentenynyl cations. These species react with benzene to afford conjugated CF3
pentenynes, which undergo subsequent cyclization, first, into CF3
cycloheptadienes and, finally, into unusual CF3-"helicopter"-like bicyclic
structures.
PMID- 29341617
TI - Enhancing Docetaxel Delivery to Multidrug-Resistant Cancer Cells with Albumin
Coated Nanocrystals.
AB - Intravenous delivery of poorly water-soluble anticancer drugs such as docetaxel
(DTX) is challenging due to the low bioavailability and the toxicity related to
solubilizing excipients. Colloidal nanoparticles are used as alternative
carriers, but low drug loading capacity and circulation instability limit their
clinical translation. To address these challenges, DTX nanocrystals (NCs) were
prepared using Pluronic F127 as an intermediate stabilizer and albumin as a
functional surface modifier, which were previously found to be effective in
producing small and stable NCs. We hypothesize that the albumin-coated DTX NCs
(DTX-F-alb) will remain stable in serum-containing medium so as to effectively
leverage the enhanced permeability and retention effect. In addition, the surface
bound albumin, in its native form, may contribute to cellular transport of NCs
through interactions with albumin-binding proteins such as secreted protein
acidic and rich in cysteine (SPARC). DTX-F-alb NCs showed sheet-like structure
with an average length, width, and thickness of 284 +/- 96, 173 +/- 56, and 40 +/
8 nm and remained stable in 50% serum solution at a concentration greater than
10 MUg/mL. Cytotoxicity and cellular uptake of DTX-F-alb and unformulated (free)
DTX were compared on three cell lines with different levels of SPARC expression
and DTX sensitivity. While the uptake of free DTX was highly dependent on DTX
sensitivity, DTX-F-alb treatment resulted in relatively consistent cellular
levels of DTX. Free DTX was more efficient in entering drug-sensitive B16F10 and
SKOV-3 cells than DTX-F-alb, with consistent cytotoxic effects. In contrast,
multidrug-resistant NCI/ADR-RES cells took up DTX-F-alb more than free DTX with
time and responded better to the former. This difference was reduced by SPARC
knockdown. The high SPARC expression level of NCI/ADR-RES cells, the known
affinity of albumin for SPARC, and the opposing effect of SPARC knockdown support
that DTX-F-alb have exploited the surface-bound albumin-SPARC interaction in
entering NCI/ADR-RES cells. Albumin-coated NC system is a promising formulation
for the delivery of hydrophobic anticancer drugs to multidrug-resistant tumors.
PMID- 29341619
TI - New Folate-Grafted Chitosan Derivative To Improve Delivery of Paclitaxel-Loaded
Solid Lipid Nanoparticles for Lung Tumor Therapy by Inhalation.
AB - Inhaled chemotherapy for the treatment of lung tumors requires that drug delivery
systems improve selectivity for cancer cells and tumor penetration and allow
sufficient lung residence. To this end, we developed solid lipid nanoparticles
(SLN) with modified surface properties. We successfully synthesized a new folate
grafted copolymer of polyethylene glycol (PEG) and chitosan, F-PEG-HTCC, with a
PEG-graft ratio of 7% and a molecular weight range of 211-250 kDa. F-PEG-HTCC
coated, paclitaxel-loaded SLN were prepared with an encapsulation efficiency,
mean diameter, and zeta potential of about 100%, 250 nm, and +32 mV,
respectively. The coated SLN entered folate receptor (FR)-expressing HeLa and
M109-HiFR cells in vitro and M109 tumors in vivo after pulmonary delivery. The
coated SLN significantly decreased the in vitro half-maximum inhibitory
concentrations of paclitaxel in M109-HiFR cells (60 vs 340 nM, respectively). We
demonstrated that FR was involved in these improvements, especially in M109-HiFR
cells. After pulmonary delivery in vivo, the coated SLN had a favorable
pharmacokinetic profile, with pulmonary exposure to paclitaxel prolonged to up to
6 h and limited systemic distribution. Our preclinical findings therefore
demonstrated the positive impact of the coated SLN on the delivery of paclitaxel
by inhalation.
PMID- 29341620
TI - Hedychins A and B, 6,7-Dinorlabdane Diterpenoids with a Peroxide Bridge from
Hedychium forrestii.
AB - Hedychins A (1) and B (2), two unprecedented 6,7-dinorlabdane ditepenoids with a
peroxide bridge, were obtained from the rhizomes of Hedychium forrestii. Their
structures and absolute configurations were unequivocally established by a
combination of spectroscopic data and X-ray single-crystal diffractions. Their
plausible biosynthetic pathway was proposed. Compound 2 exhibited cytotoxicity
against HepG2 and XWLC-05 cell lines with IC50 values of 8.0 and 19.7 MUM,
respectively.
PMID- 29341621
TI - Sustainable HandaPhos-ppm Palladium Technology for Copper-Free Sonogashira
Couplings in Water under Mild Conditions.
AB - Complexation of ca. 1000 ppm Pd(OAc)2 with the ligand HandaPhos (1-1.5:1) leads
to a precatalyst that efficiently mediates Sonogashira couplings in aqueous
nanomicelles under very mild conditions. Neither copper nor organic solvent is
required in the reaction medium, and the product can be isolated directly from
the reaction flask, leaving behind a reaction mixture that can be recycled
without additional additives.
PMID- 29341622
TI - Cyclic Peptoids as Topological Templates: Synthesis via Central to Conformational
Chirality Induction.
AB - Chiral induction was utilized for the synthesis of diastereopure cyclic peptoids
containing an N-benzyl alanine residue. Molecular modeling, NMR spectroscopy,
single-crystal X-ray diffraction studies, and HPLC with chiral stationary phase
demonstrated easy formation of free and sodium/benzylammonium complexed cyclic
oligomers through strategic incorporation of a single stereogenic center in the
oligomeric backbone. The synthesis of cyclic peptoids with defined conformational
chirality and appropriate side chain topology is now possible.
PMID- 29341623
TI - Is Subsurface Oxygen Necessary for the Electrochemical Reduction of CO2 on
Copper?
AB - It has recently been proposed that subsurface oxygen is crucial for the
adsorption and subsequent electroreduction of CO2 on copper. Using density
functional theory, we have studied the stability and diffusion of subsurface
oxygen in single crystals of copper exposing (111) and (100) facets. Oxygen is at
least 1.5 eV more stable on the surface than beneath it for both crystal
orientations; interstitial sites are too small to accommodate oxygen. The rate of
atomic oxygen diffusion from one layer below a Cu(111) surface to the surface is
5 * 103 s-1. Oxygen can survive longer in deeper layers, but it does not promote
CO2 adsorption there. Diffusion of subsurface oxygen is easier to the less-dense
Cu(100) surface, even from lower layers (rate ~ 1 * 107 s-1). Once the applied
voltage and dispersion forces are properly modeled, we find that subsurface
oxygen is unnecessary for CO2 adsorption on copper.
PMID- 29341624
TI - Regio and Enantioselective Organocatalytic Friedel-Crafts Alkylation of 4
Aminoindoles at the C7-Position.
AB - A chiral phosphoric acid catalyzed highly regio- and enantioselective Friedel
Crafts alkylation at the indole C7-position was developed via the introduction of
an alkylamine moiety at the C4-position of the indole ring. The methodology is
applicable to a wide range of 4-aminoindoles and beta,gamma-unsaturated alpha
ketimino esters to furnish the corresponding C7-position functionalized chiral
indole derivatives in high yields with moderate to excellent
enantioselectivities. Furthermore, the alpha-ketimino ester moiety in the
products is a versatile building block and enables many further transformations.
PMID- 29341625
TI - Biomimetic Total Syntheses of Callistrilones A, B, and D.
AB - A biomimetic total syntheses of antibacterial natural products (+/-)
callistrilones A, B, and D, the first triketone-phloroglucinol-monoterpene
hybrids with an unprecedented [1]benzofuro[2,3-a]xanthene and [1]benzofuro[3,2
b]xanthene pentacyclic ring system along with the postulated biosynthetic
intermediate, isolated from the leaves of Callistemon rigidus, were achieved. The
total synthesis features highly regio- and diastereoselective catalytic Friedel
Crafts alkylation, palladium-catalyzed Wacker-type oxidative cyclization, Michael
addition, and late-stage diastereoselective epoxide formation from the extremely
hindered beta face as key steps.
PMID- 29341626
TI - Hierarchically Patterned Noncovalent Functionalization of 2D Materials by
Controlled Langmuir-Schaefer Conversion.
AB - Noncovalent monolayer chemistries are often used to functionalize 2D materials.
Nanoscopic ligand ordering has been widely demonstrated (e.g., lying-down
lamellar phases of functional alkanes); however, combining this control with
micro- and macroscopic patterning for practical applications remains a
significant challenge. A few reports have demonstrated that standing phase
Langmuir films on water can be converted into nanoscopic lying-down molecular
domains on 2D substrates (e.g., graphite), using horizontal dipping (Langmuir
Schaefer, LS, transfer). Molecular patterns are known to form at scales up to
millimeters in Langmuir films, suggesting the possibility of transforming such
structures into functional patterns on 2D materials. However, to our knowledge,
this approach has not been investigated, and the rules governing LS conversion
are not well understood. In part, this is because the conversion process is
mechanistically very different from classic LS transfer of standing phases;
challenges also arise due to the need to characterize structure in noncovalently
adsorbed ligand layers <0.5 nm thick, at scales ranging from millimeters to
nanometers. Here, we show that scanning electron microscopy enables diynoic acid
lying-down phases to be imaged across this range of scales; using this structural
information, we establish conditions for LS conversion to create hierarchical
microscopic and nanoscopic functional patterns. Such control opens the door to
tailoring noncovalent surface chemistry of 2D materials to pattern local
interactions with the environment.
PMID- 29341627
TI - Ru(II)-Catalyzed Oxidative Heck-Type Olefination of Aromatic Carboxylic Acids
with Styrenes through Carboxylate-Assisted C-H Bond Activation.
AB - A straightforward synthesis of 2-styrylbenzoic acids from aryl carboxylic acids
is disclosed through a carboxylate-assisted coupling under Ru(II) catalysis. This
protocol is simple and exhibits broad scope with high tolerance of common organic
functional groups, providing good to excellent yields of diverse olefinated
products. The efficacy of this protocol has been showcased through sequential
syntheses of isochromanone, isocoumarin, and formal synthesis of anacardic acid
derivative in good yields.
PMID- 29341628
TI - Dark Matter Coannihilation with a Lighter Species.
AB - We propose a new thermal freeze-out mechanism for ultraheavy dark matter. Dark
matter coannihilates with a lighter unstable species that is nearby in mass,
leading to an annihilation rate that is exponentially enhanced relative to
standard weakly interactive massive particles. This scenario destabilizes any
potential dark matter candidate. In order to remain consistent with astrophysical
observations, our proposal necessitates very long-lived states, motivating
striking phenomenology associated with the late decays of ultraheavy dark matter,
potentially as massive as the scale of grand unified theories, M_{GUT}~10^{16}
GeV.
PMID- 29341629
TI - Mirror Charge Radii and the Neutron Equation of State.
AB - The differences in the charge radii of mirror nuclei are shown to be proportional
to the derivative of the neutron equation of state and the symmetry energy at
nuclear matter saturation density. This derivative is important for constraining
the neutron equation of state for use in astrophysics. The charge radii of
several neutron-rich nuclei are already measured to the accuracy of about 0.005
fm. Experiments at isotope-separator and radioactive-beam facilities are needed
to measure the charge radii of the corresponding proton-rich mirror nuclei to a
similar accuracy. It is also shown that neutron skins of nuclei with N=Z depend
upon the value of the symmetry energy at a density of 0.10 nucleons/fm^{3}.
PMID- 29341630
TI - Terahertz Sum-Frequency Excitation of a Raman-Active Phonon.
AB - In stimulated Raman scattering, two incident optical waves induce a force
oscillating at the difference of the two light frequencies. This process has
enabled important applications such as the excitation and coherent control of
phonons and magnons by femtosecond laser pulses. Here, we experimentally and
theoretically demonstrate the so far neglected up-conversion counterpart of this
process: THz sum-frequency excitation of a Raman-active phonon mode, which is
tantamount to two-photon absorption by an optical transition between two adjacent
vibrational levels. Coherent control of an optical lattice vibration of diamond
is achieved by an intense terahertz pulse whose spectrum is centered at half the
phonon frequency of 40 THz. Remarkably, the carrier-envelope phase of the THz
pulse is directly transferred into the phase of the lattice vibration. New
prospects in general infrared spectroscopy, action spectroscopy, and lattice
trajectory control in the electronic ground state emerge.
PMID- 29341631
TI - Rapid Transition of the Hole Rashba Effect from Strong Field Dependence to
Saturation in Semiconductor Nanowires.
AB - The electric field manipulation of the Rashba spin-orbit coupling effects
provides a route to electrically control spins, constituting the foundation of
the field of semiconductor spintronics. In general, the strength of the Rashba
effects depends linearly on the applied electric field and is significant only
for heavy-atom materials with large intrinsic spin-orbit interaction under high
electric fields. Here, we illustrate in 1D semiconductor nanowires an anomalous
field dependence of the hole (but not electron) Rashba effect (HRE). (i) At low
fields, the strength of the HRE exhibits a steep increase with the field so that
even low fields can be used for device switching. (ii) At higher fields, the HRE
undergoes a rapid transition to saturation with a giant strength even for light
atom materials such as Si (exceeding 100 meV A). (iii) The nanowire-size
dependence of the saturation HRE is rather weak for light-atom Si, so size
fluctuations would have a limited effect; this is a key requirement for
scalability of Rashba-field-based spintronic devices. These three features offer
Si nanowires as a promising platform for the realization of scalable
complementary metal-oxide-semiconductor compatible spintronic devices.
PMID- 29341632
TI - Polarizing Oxygen Vacancies in Insulating Metal Oxides under a High Electric
Field.
AB - We demonstrate a thermodynamic formulation to quantify defect formation
energetics in an insulator under a high electric field. As a model system, we
analyzed neutral oxygen vacancies (color centers) in alkaline-earth-metal binary
oxides using density functional theory, Berry phase calculations, and maximally
localized Wannier functions. The work of polarization lowers the field-dependent
electric Gibbs energy of formation of this defect. This is attributed mainly to
the ease of polarizing the two electrons trapped in the vacant site, and
secondarily to the defect induced reduction in bond stiffness and softening of
phonon modes. The formulation and analysis have implications for understanding
the behavior of insulating oxides in electronic, magnetic, catalytic, and
electrocaloric devices under a high electric field.
PMID- 29341633
TI - Universal Quantum Computing with Measurement-Induced Continuous-Variable Gate
Sequence in a Loop-Based Architecture.
AB - We propose a scalable scheme for optical quantum computing using measurement
induced continuous-variable quantum gates in a loop-based architecture. Here,
time-bin-encoded quantum information in a single spatial mode is
deterministically processed in a nested loop by an electrically programmable gate
sequence. This architecture can process any input state and an arbitrary number
of modes with almost minimum resources, and offers a universal gate set for both
qubits and continuous variables. Furthermore, quantum computing can be performed
fault tolerantly by a known scheme for encoding a qubit in an infinite
dimensional Hilbert space of a single light mode.
PMID- 29341634
TI - Publisher's Note: Ultimate Precision of Adaptive Noise Estimation [Phys. Rev.
Lett. 118, 100502 (2017)].
AB - This corrects the article DOI: 10.1103/PhysRevLett.118.100502.
PMID- 29341635
TI - Low-Field-Triggered Large Magnetostriction in Iron-Palladium Strain Glass Alloys.
AB - Development of miniaturized magnetostriction-associated devices requires low
field-triggered large magnetostriction. In this study, we acquired a large
magnetostriction (800 ppm) triggered by a low saturation field (0.8 kOe) in iron
palladium (Fe-Pd) alloys. Magnetostriction enhancement jumping from 340 to 800
ppm was obtained with a slight increase in Pd concentration from 31.3 to 32.3 at.
%. Further analysis showed that such a slight increase led to suppression of the
long-range ordered martensitic phase and resulted in a frozen short-range ordered
strain glass state. This strain glass state possessed a two-phase nanostructure
with nanosized frozen strain domains embedded in the austenite matrix, which was
responsible for the unique magnetostriction behavior. Our study provides a way to
design novel magnetostrictive materials with low-field-triggered large
magnetostriction.
PMID- 29341636
TI - Pair Potential with Submillikelvin Uncertainties and Nonadiabatic Treatment of
the Halo State of the Helium Dimer.
AB - The pair potential for helium is computed with accuracy improved by an order of
magnitude relative to the best previous determination. For the well region, its
uncertainties are now below 1 millikelvin. The main improvement is due to the use
of explicitly correlated wave functions at the nonrelativistic Born-Oppenheimer
(BO) level of theory. The diagonal BO and the relativistic corrections are
obtained from large full configuration interaction calculations. Nonadiabatic
perturbation theory is used to predict the properties of the halo state of the
helium dimer. Its binding energy and the average value of the interatomic
distance are found to be 138.9(5) neV and 47.13(8) A. The binding energy agrees
with its first experimental determination of 151.9(13.3) neV [Zeller et al.,
Proc. Natl. Acad. Sci. U.S.A. 113, 14651 (2016)PNASA60027
842410.1073/pnas.1610688113].
PMID- 29341637
TI - Enhancing Sideband Cooling by Feedback-Controlled Light.
AB - We realize a phase-sensitive closed-loop control scheme to engineer the
fluctuations of the pump field which drives an optomechanical system and show
that the corresponding cooling dynamics can be significantly improved. In
particular, operating in the counterintuitive "antisquashing" regime of positive
feedback and increased field fluctuations, sideband cooling of a nanomechanical
membrane within an optical cavity can be improved by 7.5 dB with respect to the
case without feedback. Close to the quantum regime of reduced thermal noise, such
feedback-controlled light would allow going well below the quantum backaction
cooling limit.
PMID- 29341638
TI - Quantum Communication Using Coherent Rejection Sampling.
AB - Compression of a message up to the information it carries is key to many tasks
involved in classical and quantum information theory. Schumacher [B. Schumacher,
Phys. Rev. A 51, 2738 (1995)PLRAAN1050-294710.1103/PhysRevA.51.2738] provided one
of the first quantum compression schemes and several more general schemes have
been developed ever since [M. Horodecki, J. Oppenheim, and A. Winter, Commun.
Math. Phys. 269, 107 (2007); CMPHAY0010-361610.1007/s00220-006-0118-xI. Devetak
and J. Yard, Phys. Rev. Lett. 100, 230501 (2008); PRLTAO0031
900710.1103/PhysRevLett.100.230501A. Abeyesinghe, I. Devetak, P. Hayden, and A.
Winter, Proc. R. Soc. A 465, 2537 (2009)PRLAAZ1364-502110.1098/rspa.2009.0202].
However, the one-shot characterization of these quantum tasks is still under
development, and often lacks a direct connection with analogous classical tasks.
Here we show a new technique for the compression of quantum messages with the aid
of entanglement. We devise a new tool that we call the convex split lemma, which
is a coherent quantum analogue of the widely used rejection sampling procedure in
classical communication protocols. As a consequence, we exhibit new explicit
protocols with tight communication cost for quantum state merging, quantum state
splitting, and quantum state redistribution (up to a certain optimization in the
latter case). We also present a port-based teleportation scheme which uses a
fewer number of ports in the presence of information about input.
PMID- 29341639
TI - Enhanced Second-Order Nonlinearity for THz Generation by Resonant Interaction of
Exciton-Polariton Rabi Oscillations with Optical Phonons.
AB - Semiconductor microcavities in the strong-coupling regime exhibit an energy scale
in the terahertz (THz) frequency range, which is fixed by the Rabi splitting
between the upper and lower exciton-polariton states. While this range can be
tuned by several orders of magnitude using different excitonic media, the
transition between both polaritonic states is dipole forbidden. In this work, we
show that, in cadmium telluride microcavities, the Rabi-oscillation-driven THz
radiation is actually active without the need for any change in the microcavity
design. This feature results from the unique resonance condition which is
achieved between the Rabi splitting and the phonon-polariton states and leads to
a giant enhancement of the second-order nonlinearity.
PMID- 29341640
TI - Role of Intrapulse Coherence in Carrier-Envelope Phase Stabilization.
AB - The concept of coherence is of fundamental importance for describing the physical
characteristics of light and for evaluating the suitability for experimental
application. In the case of pulsed laser sources, the pulse-to-pulse coherence is
usually considered for a judgment of the compressibility of the pulse train. This
type of coherence is often lost during propagation through a highly nonlinear
medium, and pulses prove incompressible despite multioctave spectral coverage.
Notwithstanding the apparent loss of interpulse coherence, however, supercontinua
enable applications in precision frequency metrology that rely on coherence
between different spectral components within a laser pulse. To judge the
suitability of a light source for the latter application, we define an
alternative criterion, which we term intrapulse coherence. This definition plays
a limiting role in the carrier-envelope phase measurement and stabilization of
ultrashort pulses. It is shown by numerical simulation and further corroborated
by experimental data that filamentation-based supercontinuum generation may lead
to a loss of intrapulse coherence despite near-perfect compressibility of the
pulse train. This loss of coherence may severely limit active and passive carrier
envelope phase stabilization schemes and applications in optical high-field
physics.
PMID- 29341641
TI - Simultaneous Deep Tunneling and Classical Hopping for Hydrogen Diffusion on
Metals.
AB - Hydrogen diffusion on metals exhibits rich quantum behavior, which is not yet
fully understood. Using simulations, we show that many hydrogen diffusion
barriers can be categorized into those with parabolic tops and those with broad
tops. With parabolic-top barriers, hydrogen diffusion evolves gradually from
classical hopping, to shallow tunneling, to deep tunneling as the temperature (T)
decreases, and noticeable quantum effects persist at moderate T. In contrast,
with broad-top barriers quantum effects become important only at low T and the
classical-to-quantum transition is sharp, at which classical hopping and deep
tunneling both occur. This coexistence indicates that more than one mechanism
contributes to the quantum reaction rate. The conventional definition of the
classical-to-quantum crossover T is invalid for the broad tops, and we give a new
definition. Extending this, we propose a model to predict the transition T for
broad-top diffusion, providing a general guide for theory and experiment.
PMID- 29341642
TI - Magnetic Proximity Effects in Transition-Metal Dichalcogenides: Converting
Excitons.
AB - The two-dimensional character and reduced screening in monolayer transition-metal
dichalcogenides (TMDs) lead to the ubiquitous formation of robust excitons with
binding energies orders of magnitude larger than in bulk semiconductors. Focusing
on neutral excitons, bound electron-hole pairs that dominate the optical response
in TMDs, it is shown that they can provide fingerprints for magnetic proximity
effects in magnetic heterostructures. These proximity effects cannot be described
by the widely used single-particle description but instead reveal the possibility
of a conversion between optically inactive and active excitons by rotating the
magnetization of the magnetic substrate. With recent breakthroughs in fabricating
Mo- and W-based magnetic TMD heterostructures, this emergent optical response can
be directly tested experimentally.
PMID- 29341643
TI - Generalized Magnetic Mirrors.
AB - We propose generalized magnetic mirrors that can be achieved by excitations of
sole electric resonances. Conventional approaches to obtain magnetic mirrors rely
heavily on exciting the fundamental magnetic dipoles, whereas here we reveal
that, besides magnetic resonances, electric resonances of higher orders can be
also employed to obtain highly efficient magnetic mirrors. Based on the
electromagnetic duality, it is also shown that electric mirrors can be achieved
by exciting magnetic resonances. We provide direct demonstrations of the
generalized mirrors proposed in a simple system of a one-dimensional periodic
array of all-dielectric wires, which may shed new light on many advanced fields
of photonics related to resonant multipolar excitations and interferences.
PMID- 29341644
TI - Scale-Dependent Stiffness and Internal Tension of a Model Brush Polymer.
AB - Bottle-brush polymers exhibit closely grafted side chains that interact by steric
repulsion, thereby causing stiffening of the main polymer chain. We use single
molecule elasticity measurements of model brush polymers to quantify this effect.
We find that stiffening is only significant on long length scales, with the main
chain retaining flexibility on short scales. From the elasticity data, we extract
an estimate of the internal tension generated by side-chain repulsion; this
estimate is consistent with the predictions of blob-based scaling theories.
PMID- 29341645
TI - Contextuality as a Resource for Models of Quantum Computation with Qubits.
AB - A central question in quantum computation is to identify the resources that are
responsible for quantum speed-up. Quantum contextuality has been recently shown
to be a resource for quantum computation with magic states for odd-prime
dimensional qudits and two-dimensional systems with real wave functions. The
phenomenon of state-independent contextuality poses a priori an obstruction to
characterizing the case of regular qubits, the fundamental building block of
quantum computation. Here, we establish contextuality of magic states as a
necessary resource for a large class of quantum computation schemes on qubits. We
illustrate our result with a concrete scheme related to measurement-based quantum
computation.
PMID- 29341646
TI - Erratum: Ultimate Precision of Adaptive Noise Estimation [Phys. Rev. Lett. 118,
100502 (2017)].
AB - This corrects the article DOI: 10.1103/PhysRevLett.118.100502.
PMID- 29341647
TI - Attosecond Electron Correlation Dynamics in Double Ionization of Benzene Probed
with Two-Electron Angular Streaking.
AB - With a novel three-dimensional electron-electron coincidence imaging technique
and two-electron angular streaking method, we show that the emission time delay
between two electrons can be measured from tens of attoseconds to more than 1 fs.
Surprisingly, in benzene, the double ionization rate decays as the time delay
between the first and second electron emission increases during the first 500 as.
This is further supported by the decay of the Coulomb repulsion in the direction
perpendicular to the laser polarization. This result reveals that laser-induced
electron correlation plays a major role in strong field double ionization of
benzene driven by a nearly circularly polarized field.
PMID- 29341648
TI - Thermal Transport in the Kitaev Model.
AB - In conventional insulating magnets, heat is carried by magnons and phonons. In
contrast, when the magnets harbor a quantum spin liquid state, emergent
quasiparticles from the fractionalization of quantum spins can carry heat. Here,
we investigate unconventional thermal transport yielded by such exotic carriers,
in both longitudinal and transverse components, for the Kitaev model, whose
ground state is exactly shown to be a quantum spin liquid with fractional
excitations described as itinerant Majorana fermions and localized Z_{2} fluxes.
We find that the longitudinal thermal conductivity exhibits a single peak at a
high temperature, while the nonzero frequency component has a peak at a low
temperature, reflecting the spin fractionalization. On the other hand, we show
that the transverse thermal conductivity is induced by the magnetic field in a
wide temperature range up to the energy scale of the bare exchange coupling;
while increasing temperature, the transverse response divided by temperature
decreases from the quantized value expected for the topologically nontrivial
ground state and shows nonmonotonic temperature dependence. These characteristic
behaviors provide experimentally accessible evidence of fractional excitations in
the proximity to the Kitaev quantum spin liquid.
PMID- 29341649
TI - Gaussian Hypothesis Testing and Quantum Illumination.
AB - Quantum hypothesis testing is one of the most basic tasks in quantum information
theory and has fundamental links with quantum communication and estimation
theory. In this paper, we establish a formula that characterizes the decay rate
of the minimal type-II error probability in a quantum hypothesis test of two
Gaussian states given a fixed constraint on the type-I error probability. This
formula is a direct function of the mean vectors and covariance matrices of the
quantum Gaussian states in question. We give an application to quantum
illumination, which is the task of determining whether there is a low
reflectivity object embedded in a target region with a bright thermal-noise bath.
For the asymmetric-error setting, we find that a quantum illumination transmitter
can achieve an error probability exponent stronger than a coherent-state
transmitter of the same mean photon number, and furthermore, that it requires far
fewer trials to do so. This occurs when the background thermal noise is either
low or bright, which means that a quantum advantage is even easier to witness
than in the symmetric-error setting because it occurs for a larger range of
parameters. Going forward from here, we expect our formula to have applications
in settings well beyond those considered in this paper, especially to quantum
communication tasks involving quantum Gaussian channels.
PMID- 29341650
TI - Characterization of the ^{163}Ho Electron Capture Spectrum: A Step Towards the
Electron Neutrino Mass Determination.
AB - The isotope ^{163}Ho is in many ways the best candidate to perform experiments to
investigate the value of the electron neutrino mass. It undergoes an electron
capture process to ^{163}Dy with an energy available to the decay, Q_{EC}, of
about 2.8 keV. According to the present knowledge, this is the lowest Q_{EC}
value for such transitions. Here we discuss a newly obtained spectrum of
^{163}Ho, taken by cryogenic metallic magnetic calorimeters with ^{163}Ho
implanted in the absorbers and operated in anticoincident mode for background
reduction. For the first time, the atomic deexcitation of the ^{163}Dy daughter
atom following the capture of electrons from the 5s shell in ^{163}Ho, the OI
line, was observed with a calorimetric measurement. The peak energy is determined
to be 48 eV. In addition, a precise determination of the energy available for the
decay Q_{EC}=(2.858+/-0.010_{stat}+/-0.05_{syst}) keV was obtained by analyzing
the intensities of the lines in the spectrum. This value is in good agreement
with the measurement of the mass difference between ^{163}Ho and ^{163}Dy
obtained by Penning-trap mass spectrometry, demonstrating the reliability of the
calorimetric technique.
PMID- 29341651
TI - Lattice Homotopy Constraints on Phases of Quantum Magnets.
AB - The Lieb-Schultz-Mattis (LSM) theorem and its extensions forbid trivial phases
from arising in certain quantum magnets. Constraining infrared behavior with the
ultraviolet data encoded in the microscopic lattice of spins, these theorems tie
the absence of spontaneous symmetry breaking to the emergence of exotic phases
like quantum spin liquids. In this work, we take a new topological perspective on
these theorems, by arguing they originate from an obstruction to "trivializing"
the lattice under smooth, symmetric deformations, which we call the "lattice
homotopy problem." We conjecture that all LSM-like theorems for quantum magnets
(many previously unknown) can be understood from lattice homotopy, which
automatically incorporates the full spatial symmetry group of the lattice,
including all its point-group symmetries. One consequence is that any spin
symmetric magnet with a half-integer moment on a site with even-order rotational
symmetry must be a spin liquid. To substantiate the claim, we prove the
conjecture in two dimensions for some physically relevant settings.
PMID- 29341652
TI - Cascade of Magnetic-Field-Induced Lifshitz Transitions in the Ferromagnetic Kondo
Lattice Material YbNi_{4}P_{2}.
AB - A ferromagnetic quantum critical point is thought not to exist in two- and three
dimensional metallic systems yet is realized in the Kondo lattice compound
YbNi_{4}(P,As)_{2}, possibly due to its one-dimensionality. It is crucial to
investigate the dimensionality of the Fermi surface of YbNi_{4}P_{2}
experimentally, but common probes such as angle-resolved photoemission
spectroscopy and quantum oscillation measurements are lacking. Here, we study the
magnetic-field dependence of transport and thermodynamic properties of
YbNi_{4}P_{2}. The Kondo effect is continuously suppressed, and additionally we
identify nine Lifshitz transitions between 0.4 and 18 T. We analyze the transport
coefficients in detail and identify the type of Lifshitz transitions as neck or
void type to gain information on the Fermi surface of YbNi_{4}P_{2}. The large
number of Lifshitz transitions observed within this small energy window is
unprecedented and results from the particular flat renormalized band structure
with strong 4f-electron character shaped by the Kondo lattice effect.
PMID- 29341653
TI - Quantum Nonlinear Optics in Optomechanical Nanoscale Waveguides.
AB - We show that strong nonlinearities at the few photon level can be achieved in
optomechanical nanoscale waveguides. We consider the propagation of photons in cm
scale one-dimensional nanophotonic structures where stimulated Brillouin
scattering (SBS) is strongly enhanced by radiation pressure coupling. We
introduce a configuration that allows slowing down photons by several orders of
magnitude via SBS from sound waves using two pump fields. Slowly propagating
photons can then experience strong nonlinear interactions through virtual off
resonant exchange of dispersionless phonons. As a benchmark we identify
requirements for achieving a large cross-phase modulation among two
counterpropagating photons applicable for photonic quantum gates. Our results
indicate that strongly nonlinear quantum optics is possible in continuum
optomechanical systems realized in nanophotonic structures.
PMID- 29341654
TI - Revealing Nonclassicality of Inaccessible Objects.
AB - Some physical objects are hardly accessible to direct experimentation. It is then
desirable to infer their properties based solely on the interactions they have
with systems over which we have control. In this spirit, here we introduce
schemes for assessing the nonclassicality of the inaccessible objects as
characterized by quantum discord. We consider two probes individually interacting
with the inaccessible object but not with each other. The schemes are based on
monitoring entanglement dynamics between the probes. Our method is robust and
experimentally friendly, as it allows the probes and the object to be open
systems and makes no assumptions about the initial state, dimensionality of
involved Hilbert spaces, and details of the probe-object Hamiltonian. We apply
our scheme to a membrane-in-the-middle optomechanical system, to detect system
environment correlations in open system dynamics as well as nonclassicality of
the environment, and we foresee potential benefits for the inference of the
nonclassical nature of gravity.
PMID- 29341655
TI - Plasmons in Dimensionally Mismatched Coulomb Coupled Graphene Systems.
AB - We calculate the plasmon dispersion relation for Coulomb coupled metallic
armchair graphene nanoribbons and doped monolayer graphene. The crossing of the
plasmon curves, which occurs for uncoupled 1D and 2D systems, is split by the
interlayer Coulomb coupling into a lower and an upper plasmon branch. The upper
branch exhibits an unusual behavior with end points at finite q. Accordingly, the
structure factor shows either a single or a double peak behavior, depending on
the plasmon wavelength. The new plasmon structure is relevant to recent
experiments, its properties can be controlled by varying the system parameters
and be used in plasmonic applications.
PMID- 29341656
TI - Quantum Correlations in Nonlocal Boson Sampling.
AB - Determination of the quantum nature of correlations between two spatially
separated systems plays a crucial role in quantum information science. Of
particular interest is the questions of if and how these correlations enable
quantum information protocols to be more powerful. Here, we report on a
distributed quantum computation protocol in which the input and output quantum
states are considered to be classically correlated in quantum informatics.
Nevertheless, we show that the correlations between the outcomes of the
measurements on the output state cannot be efficiently simulated using classical
algorithms. Crucially, at the same time, local measurement outcomes can be
efficiently simulated on classical computers. We show that the only known
classicality criterion violated by the input and output states in our protocol is
the one used in quantum optics, namely, phase-space nonclassicality. As a result,
we argue that the global phase-space nonclassicality inherent within the output
state of our protocol represents true quantum correlations.
PMID- 29341657
TI - Triple Junction at the Triple Point Resolved on the Individual Particle Level.
AB - At the triple point of a repulsive screened Coulomb system, a fcc crystal, a bcc
crystal, and a fluid phase coexist. At their intersection, these three phases
form a liquid groove, the triple junction. Using confocal microscopy, we resolve
the triple junction on a single-particle level in a model system of charged PMMA
colloids in a nonpolar solvent. The groove is found to be extremely deep and the
incommensurate solid-solid interface to be very broad. Thermal fluctuations hence
appear to dominate the solid-solid interface. This indicates a very low
interfacial energy. The fcc-bcc interfacial energy is quantitatively determined
based on Young's equation and, indeed, it is only about 1.3 times higher than the
fcc-fluid interfacial energy close to the triple point.
PMID- 29341658
TI - Floquet Symmetry-Protected Topological Phases in Cold-Atom Systems.
AB - We propose and analyze two distinct routes toward realizing interacting symmetry
protected topological (SPT) phases via periodic driving. First, we demonstrate
that a driven transverse-field Ising model can be used to engineer complex
interactions which enable the emulation of an equilibrium SPT phase. This phase
remains stable only within a parametric time scale controlled by the driving
frequency, beyond which its topological features break down. To overcome this
issue, we consider an alternate route based upon realizing an intrinsically
Floquet SPT phase that does not have any equilibrium analog. In both cases, we
show that disorder, leading to many-body localization, prevents runaway heating
and enables the observation of coherent quantum dynamics at high energy
densities. Furthermore, we clarify the distinction between the equilibrium and
Floquet SPT phases by identifying a unique micromotion-based entanglement
spectrum signature of the latter. Finally, we propose a unifying implementation
in a one-dimensional chain of Rydberg-dressed atoms and show that protected edge
modes are observable on realistic experimental time scales.
PMID- 29341659
TI - New Boundary-Driven Twist States in Systems with Broken Spatial Inversion
Symmetry.
AB - A full description of a magnetic sample includes a correct treatment of the
boundary conditions (BCs). This is in particular important in thin film systems,
where even bulk properties might be modified by the properties of the boundary of
the sample. We study generic ferromagnets with broken spatial inversion symmetry
and derive the general micromagnetic BCs of a system with Dzyaloshinskii-Moriya
interaction (DMI). We demonstrate that the BCs require the full tensorial
structure of the third-rank DMI tensor and not just the antisymmetric part, which
is usually taken into account. Specifically, we study systems with C_{infinityv}
symmetry and explore the consequences of the DMI. Interestingly, we find that the
DMI already in the simplest case of a ferromagnetic thin film leads to a purely
boundary-driven magnetic twist state at the edges of the sample. The twist state
represents a new type of DMI-induced spin structure, which is completely
independent of the internal DMI field. We estimate the size of the texture
induced magnetoresistance effect being in the range of that of domain walls.
PMID- 29341660
TI - 2D Stress Tensor for 4D Gravity.
AB - We use the subleading soft-graviton theorem to construct an operator T_{zz} whose
insertion in the four-dimensional tree-level quantum gravity S matrix obeys the
Virasoro-Ward identities of the energy momentum tensor of a two-dimensional
conformal field theory (CFT_{2}). The celestial sphere at Minkowskian null
infinity plays the role of the Euclidean sphere of the CFT_{2}, with the Lorentz
group acting as the unbroken SL(2,C) subgroup.
PMID- 29341661
TI - Entanglement Hamiltonians for Chiral Fermions with Zero Modes.
AB - In this Letter, we study the effect of topological zero modes on entanglement
Hamiltonians and the entropy of free chiral fermions in (1+1)D. We show how
Riemann-Hilbert solutions combined with finite rank perturbation theory allow us
to obtain exact expressions for entanglement Hamiltonians. In the absence of the
zero mode, the resulting entanglement Hamiltonians consist of local and bilocal
terms. In the periodic sector, the presence of a zero mode leads to an additional
nonlocal contribution to the entanglement Hamiltonian. We derive an exact
expression for this term and for the resulting change in the entanglement
entropy.
PMID- 29341662
TI - Reentrant Phase Diagram of Yb_{2}Ti_{2}O_{7} in a ?111? Magnetic Field.
AB - We present a magnetic phase diagram of rare-earth pyrochlore Yb_{2}Ti_{2}O_{7} in
a ?111? magnetic field. Using heat capacity, magnetization, and neutron
scattering data, we show an unusual field dependence of a first-order phase
boundary, wherein a small applied field increases the ordering temperature. The
zero-field ground state has ferromagnetic domains, while the spins polarize along
?111? above 0.65 T. A classical Monte Carlo analysis of published Hamiltonians
does account for the critical field in the low T limit. However, this analysis
fails to account for the large bulge in the reentrant phase diagram, suggesting
that either long-range interactions or quantum fluctuations govern low field
properties.
PMID- 29341663
TI - Conditional Hybrid Nonclassicality.
AB - We derive and implement a general method to characterize the nonclassicality in
compound discrete- and continuous-variable systems. For this purpose, we
introduce the operational notion of conditional hybrid nonclassicality which
relates to the ability to produce a nonclassical continuous-variable state by
projecting onto a general superposition of discrete-variable subsystem. We
discuss the importance of this form of quantumness in connection with interfaces
for quantum communication. To verify the conditional hybrid nonclassicality, a
matrix version of a nonclassicality quasiprobability is derived and its sampling
approach is formulated. We experimentally generate an entangled, hybrid
Schrodinger cat state, using a coherent photon-addition process acting on two
temporal modes, and we directly sample its nonclassicality quasiprobability
matrix. The introduced conditional quantum effects are certified with high
statistical significance.
PMID- 29341664
TI - Optimal Continuous Variable Quantum Teleportation with Limited Resources.
AB - Given a certain amount of entanglement available as a resource, what is the most
efficient way to accomplish a quantum task? We address this question in the
relevant case of continuous variable quantum teleportation protocols implemented
using two-mode Gaussian states with a limited degree of entanglement and energy.
We first characterize the class of single-mode phase-insensitive Gaussian
channels that can be simulated via a Braunstein-Kimble protocol with nonunit gain
and minimum shared entanglement, showing that infinite energy is not necessary
apart from the special case of the quantum limited attenuator. We also find that
apart from the identity, all phase-insensitive Gaussian channels can be simulated
through a two-mode squeezed state with finite energy, albeit with a larger
entanglement. We then consider the problem of teleporting single-mode coherent
states with Gaussian-distributed displacement in phase space. Performing a
geometrical optimization over phase-insensitive Gaussian channels, we determine
the maximum average teleportation fidelity achievable with any finite
entanglement and for any realistically finite variance of the input distribution.
PMID- 29341665
TI - Can Hail and Rain Nucleate Cloud Droplets?
AB - We present results from moist convection in a mixture of pressurized sulfur
hexafluoride (liquid and vapor), and helium (gas) to model the wet and dry
components of the Earth's atmosphere. To allow for homogeneous nucleation, we
operate the experiment close to critical conditions. We report on the nucleation
of microdroplets in the wake of large cold liquid drops falling through the
supersaturated atmosphere and show that the homogeneous nucleation is caused by
isobaric cooling of the saturated sulfur hexafluoride vapor. Our results carry
over to atmospheric clouds: falling hail and cold rain drops may enhance the
heterogeneous nucleation of microdroplets in their wake under supersaturated
atmospheric conditions. We also observed that under appropriate circumstances
settling microdroplets form a rather stable horizontal cloud layer, which
separates regions of super- and subcritical saturation.
PMID- 29341666
TI - Mechanism behind Erosive Bursts In Porous Media.
AB - Erosion and deposition during flow through porous media can lead to large erosive
bursts that manifest as jumps in permeability and pressure loss. Here we reveal
that the cause of these bursts is the reopening of clogged pores when the
pressure difference between two opposite sites of the pore surpasses a certain
threshold. We perform numerical simulations of flow through porous media and
compare our predictions to experimental results, recovering with excellent
agreement shape and power-law distribution of pressure loss jumps, and the
behavior of the permeability jumps as a function of particle concentration.
Furthermore, we find that erosive bursts only occur for pressure gradient
thresholds within the range of two critical values, independent of how the flow
is driven. Our findings provide a better understanding of sudden sand production
in oil wells and breakthrough in filtration.
PMID- 29341667
TI - Dark Kinetic Heating of Neutron Stars and an Infrared Window on WIMPs, SIMPs, and
Pure Higgsinos.
AB - We identify a largely model-independent signature of dark matter (DM)
interactions with nucleons and electrons. DM in the local galactic halo,
gravitationally accelerated to over half the speed of light, scatters against and
deposits kinetic energy into neutron stars, heating them to infrared blackbody
temperatures. The resulting radiation could potentially be detected by the James
Webb Space Telescope, the Thirty Meter Telescope, or the European Extremely Large
Telescope. This mechanism also produces optical emission from neutron stars in
the galactic bulge, and x-ray emission near the galactic center because dark
matter is denser in these regions. For GeV-PeV mass dark matter, dark kinetic
heating would initially unmask any spin-independent or spin-dependent dark matter
nucleon cross sections exceeding 2*10^{-45} cm^{2}, with improved sensitivity
after more telescope exposure. For lighter-than-GeV dark matter, cross-section
sensitivity scales inversely with dark matter mass because of Pauli blocking; for
heavier-than-PeV dark matter, it scales linearly with mass as a result of needing
multiple scatters for capture. Future observations of dark sector-warmed neutron
stars could determine whether dark matter annihilates in or only kinetically
heats neutron stars. Because inelastic interstate transitions of up to a few GeV
would occur in relativistic scattering against nucleons, elusive inelastic dark
matter like pure Higgsinos can also be discovered.
PMID- 29341668
TI - Modular Invariance of Conformal Field Theory on S^{1}*S^{3} and Circle
Fibrations.
AB - I conjecture a high-temperature-low-temperature duality for conformal field
theories defined on circle fibrations like S^{3} and its lens space family. The
duality is an exchange between the thermal circle and the fiber circle in the
limit where both are small. The conjecture is motivated by the fact that
pi_{1}(S^{3}/Z_{p->infinity})=Z=pi_{1}(S^{1}*S^{2}) and the Gromov-Hausdorff
distance between S^{3}/Z_{p->infinity} and S^{1}/Z_{p->infinity}*S^{2} vanishes.
Several checks of the conjecture are provided: free fields, N=1 theories in four
dimensions (which shows that the Di Pietro-Komargodski supersymmetric Cardy
formula and its generalizations are given exactly by a supersymmetric Casimir
energy), N=4 super Yang-Mills at strong coupling, and the six-dimensional N=(2,0)
theory. For all examples considered, the duality is powerful enough to control
the high-temperature asymptotics on the unlensed S^{3}, relating it to the
Casimir energy on a highly lensed S^{3}. Such large-order quotients are more
generally useful for studying quantum field theory on curved spacetimes.
PMID- 29341669
TI - Precision Measurement of Time-Reversal Symmetry Violation with Laser-Cooled
Polyatomic Molecules.
AB - Precision searches for time-reversal symmetry violating interactions in polar
molecules are extremely sensitive probes of high energy physics beyond the
standard model. To extend the reach of these probes into the PeV regime, long
coherence times and large count rates are necessary. Recent advances in laser
cooling of polar molecules offer one important tool-optical trapping. However,
the types of molecules that have been laser cooled so far do not have the highly
desirable combination of features for new physics searches, such as the ability
to fully polarize and the existence of internal comagnetometer states. We show
that by utilizing the internal degrees of freedom present only in molecules with
at least three atoms, these features can be attained simultaneously with
molecules that have simple structure and are amenable to laser cooling and
trapping.
PMID- 29341670
TI - Surface Polarization Effects on Ion-Containing Emulsions.
AB - Surface polarization in ion-containing heterogeneous dielectric media such as
cell media and emulsions is determined by and determines the positions of the
ions. We compute the surface polarization self-consistently as the ions move and
analyze their effects on the interactions between electro-neutral, ion-containing
droplets using coarse-grained molecular dynamics simulations based on the true
energy functional. For water droplets immersed in oil, the interdroplet
interaction is attractive, and the surface polarization makes the major
contribution. By contrast, for oil droplets in water, the ion-surface induced
charge interaction is repulsive and counteracts the attraction between the ions,
leading to a small attractive interaction between the droplets. This research
improves our understanding of self-assembly in mixed phases such as metal
extraction for recovering rare earth elements and nuclear waste as well as water
purification.
PMID- 29341671
TI - Ab initio Exchange-Correlation Free Energy of the Uniform Electron Gas at Warm
Dense Matter Conditions.
AB - In a recent Letter [T. Dornheim et al., Phys. Rev. Lett. 117, 156403
(2016)PRLTAO0031-900710.1103/PhysRevLett.117.156403], we presented the first
quantum Monte Carlo (QMC) results for the warm dense electron gas in the
thermodynamic limit. However, a complete parametrization of the exchange
correlation free energy with respect to density, temperature, and spin
polarization remained out of reach due to the absence of (i) accurate QMC results
below theta=k_{B}T/E_{F}=0.5 and (ii) QMC results for spin polarizations
different from the paramagnetic case. Here we overcome both remaining
limitations. By closing the gap to the ground state and by performing extensive
QMC simulations for different spin polarizations, we are able to obtain the first
completely ab initio exchange-correlation free energy functional; the accuracy
achieved is an unprecedented ~0.3%. This also allows us to quantify the accuracy
and systematic errors of various previous approximate functionals.
PMID- 29341672
TI - Helicase Stepping Investigated with One-Nucleotide Resolution Fluorescence
Resonance Energy Transfer.
AB - Single-molecule Forster resonance energy transfer is widely applied to study
helicases by detecting distance changes between a pair of dyes anchored to
overhangs of a forked DNA. However, it has been lacking single-base pair (1-bp)
resolution required for revealing stepping kinetics of helicases. We designed a
nanotensioner in which a short DNA is bent to exert force on the overhangs, just
as in optical or magnetic tweezers. The strategy improved the resolution of
Forster resonance energy transfer to 0.5 bp, high enough to uncover differences
in DNA unwinding by yeast Pif1 and E. coli RecQ whose unwinding behaviors cannot
be differentiated by currently practiced methods. We found that Pif1 exhibits 1
bp-stepping kinetics, while RecQ breaks 1 bp at a time but sequesters the nascent
nucleotides and releases them randomly. The high-resolution data allowed us to
propose a three-parameter model to quantitatively interpret the apparently
different unwinding behaviors of the two helicases which belong to two
superfamilies.
PMID- 29341673
TI - Chiral Spin Mode on the Surface of a Topological Insulator.
AB - Using polarization-resolved resonant Raman spectroscopy, we explore collective
spin excitations of the chiral surface states in a three dimensional topological
insulator, Bi_{2}Se_{3}. We observe a sharp peak at 150 meV in the pseudovector
A_{2} symmetry channel of the Raman spectra. By comparing the data with
calculations, we identify this peak as the transverse collective spin mode of
surface Dirac fermions. This mode, unlike a Dirac plasmon or a surface plasmon in
the charge sector of excitations, is analogous to a spin wave in a partially
polarized Fermi liquid, with spin-orbit coupling playing the role of an effective
magnetic field.
PMID- 29341674
TI - Stochastic and Resolvable Gravitational Waves from Ultralight Bosons.
AB - Ultralight scalar fields around spinning black holes can trigger superradiant
instabilities, forming a long-lived bosonic condensate outside the horizon. We
use numerical solutions of the perturbed field equations and astrophysical models
of massive and stellar-mass black hole populations to compute, for the first
time, the stochastic gravitational-wave background from these sources. In
optimistic scenarios the background is observable by Advanced LIGO and LISA for
field masses m_{s} in the range ~[2*10^{-13},10^{-12}] and ~5*[10^{-19},10^{-16}]
eV, respectively, and it can affect the detectability of resolvable sources. Our
estimates suggest that an analysis of the stochastic background limits from LIGO
O1 might already be used to marginally exclude axions with mass ~10^{-12.5} eV.
Semicoherent searches with Advanced LIGO (LISA) should detect ~15(5) to 200(40)
resolvable sources for scalar field masses 3*10^{-13} (10^{-17}) eV. LISA
measurements of massive BH spins could either rule out bosons in the range ~[10^{
18},2*10^{-13}] eV, or measure m_{s} with 10% accuracy in the range ~[10^{
17},10^{-13}] eV.
PMID- 29341675
TI - Many-Molecule Reaction Triggered by a Single Photon in Polaritonic Chemistry.
AB - The second law of photochemistry states that, in most cases, no more than one
molecule is activated for an excited-state reaction for each photon absorbed by a
collection of molecules. In this Letter, we demonstrate that it is possible to
trigger a many-molecule reaction using only one photon by strongly coupling the
molecular ensemble to a confined light mode. The collective nature of the
resulting hybrid states of the system (the so-called polaritons) leads to the
formation of a polaritonic "supermolecule" involving the degrees of freedom of
all molecules, opening a reaction path on which all involved molecules undergo a
chemical transformation. We theoretically investigate the system conditions for
this effect to take place and be enhanced.
PMID- 29341676
TI - Excess Hydrogen Bond at the Ice-Vapor Interface around 200 K.
AB - Phase-resolved sum-frequency generation measurements combined with molecular
dynamics simulations are employed to study the effect of temperature on the
molecular arrangement of water on the basal face of ice. The topmost monolayer,
interrogated through its nonhydrogen-bonded, free O-H stretch peak, exhibits a
maximum in surface H-bond density around 200 K. This maximum results from two
competing effects: above 200 K, thermal fluctuations cause the breaking of H
bonds; below 200 K, the formation of bulklike crystalline interfacial structures
leads to H-bond breaking. Knowledge of the surface structure of ice is critical
for understanding reactions occurring on ice surfaces and ice nucleation.
PMID- 29341677
TI - Current-Nonlinear Hall Effect and Spin-Orbit Torque Magnetization Switching in a
Magnetic Topological Insulator.
AB - The current-nonlinear Hall effect or second harmonic Hall voltage is widely used
as one of the methods for estimating charge-spin conversion efficiency, which is
attributed to the magnetization oscillation by spin-orbit torque (SOT). Here, we
argue the second harmonic Hall voltage under a large in-plane magnetic field with
an in-plane magnetization configuration in magnetic-nonmagnetic topological
insulator (TI) heterostructures, Cr_{x}(Bi_{1-y}Sb_{y})_{2-x}Te_{3}/(Bi_{1
y}Sb_{y})_{2}Te_{3}, where it is clearly shown that the large second harmonic
voltage is governed not by SOT but mainly by asymmetric magnon scattering without
macroscopic magnetization oscillation. Thus, this method does not allow an
accurate estimation of charge-spin conversion efficiency in TI. Instead, the SOT
contribution is exemplified by current pulse induced nonvolatile magnetization
switching, which is realized with a current density of 2.5*10^{10} A m^{-2},
showing its potential as a spintronic material.
PMID- 29341678
TI - Erratum: Distinct Turbulence Saturation Regimes in Stellarators [Phys. Rev. Lett.
118, 105002 (2017)].
AB - This corrects the article DOI: 10.1103/PhysRevLett.118.105002.
PMID- 29341679
TI - Detection of the Spin-Chemical Potential in Topological Insulators Using Spin
Polarized Four-Probe STM.
AB - We demonstrate a new method for the detection of the spin-chemical potential in
topological insulators using spin-polarized four-probe scanning tunneling
microscopy on in situ cleaved Bi_{2}Te_{2}Se surfaces. Two-dimensional (2D)
surface and 3D bulk conductions are separated quantitatively via variable probe
spacing measurements, enabling the isolation of the nonvanishing spin-dependent
electrochemical potential from the Ohmic contribution. This component is
identified as the spin-chemical potential arising from the 2D charge current
through the spin momentum locked topological surface states (TSS). This method
provides a direct measurement of spin current generation efficiency and opens a
new avenue to access the intrinsic spin transport associated with pristine TSS.
PMID- 29341681
TI - Determining Quiescent Colloidal Suspension Viscosities Using the Green-Kubo
Relation and Image-Based Stress Measurements.
AB - By combining confocal microscopy and stress assessment from local structural
anisotropy, we directly measure stresses in 3D quiescent colloidal liquids. Our
noninvasive and nonperturbative method allows us to measure forces ?50 fN with a
small and tunable probing volume, enabling us to resolve the stress fluctuations
arising from particle thermal motions. We use the Green-Kubo relation to relate
these measured stress fluctuations to the bulk Brownian viscosity at different
volume fractions, comparing against simulations and conventional rheometry
measurements. We find that the Green-Kubo analysis gives excellent agreement with
these prior results, suggesting that similar methods could be applied to
investigations of local flow properties in many poorly understood far-from
equilibrium systems, including suspensions that are glassy, strongly sheared, or
highly confined.
PMID- 29341680
TI - Ultimate Stable Underwater Superhydrophobic State.
AB - Underwater metastability hinders the durable application of superhydrophobic
surfaces. In this work, through thermodynamic analysis, we theoretically
demonstrate the existence of an ultimate stable state on underwater
superhydrophobic surfaces. Such a state is achieved by the synergy of mechanical
balance and chemical diffusion equilibrium across the entrapped liquid-air
interfaces. By using confocal microscopy, we in situ examine the ultimate stable
states on structured hydrophobic surfaces patterned with cylindrical micropores
in different pressure and flow conditions. The equilibrium morphology of the
meniscus is tuned by the dissolved gas saturation degree within a critical range
at a given liquid pressure. Moreover, with fresh lotus leaves, we prove that the
ultimate stable state can also be realized on randomly rough superhydrophobic
surfaces. The finding here paves the way for applying superhydrophobic surfaces
in environments with different liquid pressure and flow conditions.
PMID- 29341682
TI - Gate-Controlled Spin-Valley Locking of Resident Carriers in WSe_{2} Monolayers.
AB - Using time-resolved Kerr rotation, we measure the spin-valley dynamics of
resident electrons and holes in single charge-tunable monolayers of the
archetypal transition-metal dichalcogenide (TMD) semiconductor WSe_{2}. In the n
type regime, we observe long (~130 ns) polarization relaxation of electrons that
is sensitive to in-plane magnetic fields B_{y}, indicating spin relaxation. In
marked contrast, extraordinarily long (~2 MUs) polarization relaxation of holes
is revealed in the p-type regime, which is unaffected by B_{y}, directly
confirming long-standing expectations of strong spin-valley locking of holes in
the valence band of monolayer TMDs. Supported by continuous-wave Kerr
spectroscopy and Hanle measurements, these studies provide a unified picture of
carrier polarization dynamics in monolayer TMDs, which can guide design
principles for future valleytronic devices.
PMID- 29341683
TI - Theory of Thermal Relaxation of Electrons in Semiconductors.
AB - We compute the transient dynamics of phonons in contact with high energy "hot"
charge carriers in 12 polar and nonpolar semiconductors, using a first-principles
Boltzmann transport framework. For most materials, we find that the decay in
electronic temperature departs significantly from a single-exponential model at
times ranging from 1 to 15 ps after electronic excitation, a phenomenon
concomitant with the appearance of nonthermal vibrational modes. We demonstrate
that these effects result from slow thermalization within the phonon subsystem,
caused by the large heterogeneity in the time scales of electron-phonon and
phonon-phonon interactions in these materials. We propose a generalized two
temperature model accounting for phonon thermalization as a limiting step of
electron-phonon thermalization, which captures the full thermal relaxation of hot
electrons and holes in semiconductors. A direct consequence of our findings is
that, for semiconductors, information about the spectral distribution of electron
phonon and phonon-phonon coupling can be extracted from the multiexponential
behavior of the electronic temperature.
PMID- 29341684
TI - First Simultaneous Extraction of Spin-Dependent Parton Distributions and
Fragmentation Functions from a Global QCD Analysis.
AB - We perform the first global QCD analysis of polarized inclusive and semi
inclusive deep-inelastic scattering and single-inclusive e^{+}e^{-} annihilation
data, simultaneously fitting the parton distribution and fragmentation functions
using the iterative Monte Carlo method. Without imposing SU(3) symmetry
relations, we find the strange polarization to be very small, consistent with
zero for both inclusive and semi-inclusive data, which provides a resolution to
the strange quark polarization puzzle. The combined analysis also allows the
direct extraction from data of the isovector and octet axial charges, and is
consistent with a small SU(2) flavor asymmetry in the polarized sea.
PMID- 29341685
TI - Intermittent Granular Dynamics at a Seismogenic Plate Boundary.
AB - Earthquakes at seismogenic plate boundaries are a response to the differential
motions of tectonic blocks embedded within a geometrically complex network of
branching and coalescing faults. Elastic strain is accumulated at a slow strain
rate on the order of 10^{-15} s^{-1}, and released intermittently at intervals
>100 yr, in the form of rapid (seconds to minutes) coseismic ruptures. The
development of macroscopic models of quasistatic planar tectonic dynamics at
these plate boundaries has remained challenging due to uncertainty with regard to
the spatial and kinematic complexity of fault system behaviors. The
characteristic length scale of kinematically distinct tectonic structures is
particularly poorly constrained. Here, we analyze fluctuations in Global
Positioning System observations of interseismic motion from the southern
California plate boundary, identifying heavy-tailed scaling behavior. Namely, we
show that, consistent with findings for slowly sheared granular media, the
distribution of velocity fluctuations deviates from a Gaussian, exhibiting broad
tails, and the correlation function decays as a stretched exponential. This
suggests that the plate boundary can be understood as a densely packed granular
medium, predicting a characteristic tectonic length scale of 91+/-20 km, here
representing the characteristic size of tectonic blocks in the southern
California fault network, and relating the characteristic duration and recurrence
interval of earthquakes, with the observed sheared strain rate, and the
nanosecond value for the crack tip evolution time scale. Within a granular
description, fault and blocks systems may rapidly rearrange the distribution of
forces within them, driving a mixture of transient and intermittent fault slip
behaviors over tectonic time scales.
PMID- 29341686
TI - Nonequilibrium Chromosome Looping via Molecular Slip Links.
AB - We propose a model for the formation of chromatin loops based on the diffusive
sliding of molecular slip links. These mimic the behavior of molecules like
cohesin, which, along with the CTCF protein, stabilize loops which contribute to
organizing the genome. By combining 3D Brownian dynamics simulations and 1D
exactly solvable nonequilibrium models, we show that diffusive sliding is
sufficient to account for the strong bias in favor of convergent CTCF-mediated
chromosome loops observed experimentally. We also find that the diffusive motion
of multiple slip links along chromatin is rectified by an intriguing ratchet
effect that arises if slip links bind to the chromatin at a preferred "loading
site." This emergent collective behavior favors the extrusion of loops which are
much larger than the ones formed by single slip links.
PMID- 29341687
TI - Maximally Symmetric Composite Higgs Models.
AB - Maximal symmetry is a novel tool for composite pseudo Goldstone boson Higgs
models: it is a remnant of an enhanced global symmetry of the composite fermion
sector involving a twisting with the Higgs field. Maximal symmetry has far
reaching consequences: it ensures that the Higgs potential is finite and fully
calculable, and also minimizes the tuning. We present a detailed analysis of the
maximally symmetric SO(5)/SO(4) model and comment on its observational
consequences.
PMID- 29341688
TI - What Randomized Benchmarking Actually Measures.
AB - Randomized benchmarking (RB) is widely used to measure an error rate of a set of
quantum gates, by performing random circuits that would do nothing if the gates
were perfect. In the limit of no finite-sampling error, the exponential decay
rate of the observable survival probabilities, versus circuit length, yields a
single error metric r. For Clifford gates with arbitrary small errors described
by process matrices, r was believed to reliably correspond to the mean, over all
Clifford gates, of the average gate infidelity between the imperfect gates and
their ideal counterparts. We show that this quantity is not a well-defined
property of a physical gate set. It depends on the representations used for the
imperfect and ideal gates, and the variant typically computed in the literature
can differ from r by orders of magnitude. We present new theories of the RB decay
that are accurate for all small errors describable by process matrices, and show
that the RB decay curve is a simple exponential for all such errors. These
theories allow explicit computation of the error rate that RB measures (r), but
as far as we can tell it does not correspond to the infidelity of a physically
allowed (completely positive) representation of the imperfect gates.
PMID- 29341689
TI - Prediction of Triple Point Fermions in Simple Half-Heusler Topological
Insulators.
AB - We predict the existence of triple point fermions in the band structure of
several half-Heusler topological insulators by ab initio calculations and the
Kane model. We find that many half-Heusler compounds exhibit multiple triple
points along four independent C_{3} axes, through which the doubly degenerate
conduction bands and the nondegenerate valence band cross each other linearly
nearby the Fermi energy. When projected from the bulk to the (111) surface, most
of these triple points are located far away from the surface Gamma[over -] point,
as distinct from previously reported triple point fermion candidates. These
isolated triple points give rise to Fermi arcs on the surface, that can be
readily detected by photoemission spectroscopy or scanning tunneling
spectroscopy.
PMID- 29341690
TI - Anomalous Nonlocal Resistance and Spin-Charge Conversion Mechanisms in Two
Dimensional Metals.
AB - We uncover two anomalous features in the nonlocal transport behavior of two
dimensional metallic materials with spin-orbit coupling. First, the nonlocal
resistance can have negative values and oscillate with distance, even in the
absence of a magnetic field. Second, the oscillations of the nonlocal resistance
under an applied in-plane magnetic field (the Hanle effect) can be asymmetric
under field reversal. Both features are produced by direct magnetoelectric
coupling, which is possible in materials with broken inversion symmetry but was
not included in previous spin-diffusion theories of nonlocal transport. These
effects can be used to identify the relative contributions of different spin
charge conversion mechanisms. They should be observable in adatom-functionalized
graphene, and they may provide the reason for discrepancies in recent nonlocal
transport experiments on graphene.
PMID- 29341691
TI - Dissipative Effects on Inertial-Range Statistics at High Reynolds Numbers.
AB - Using the unique capabilities of the Variable Density Turbulence Tunnel at the
Max Planck Institute for Dynamics and Self-Organization, Gottingen, we report
experimental measurements in classical grid turbulence that uncover oscillations
of the velocity structure functions in the inertial range. This was made possible
by measuring extremely long time series of up to 10^{10} samples of the turbulent
fluctuating velocity, which corresponds to O(10^{7}) integral length scales. The
measurements were conducted in a well-controlled environment at a wide range of
high Reynolds numbers from R_{lambda}=110 up to R_{lambda}=1600, using both
traditional hot-wire probes as well as the nanoscale thermal anemometry probe
developed at Princeton University. An implication of the observed oscillations is
that dissipation influences the inertial-range statistics of turbulent flows at
scales significantly larger than predicted by current models and theories.
PMID- 29341692
TI - Nontrivial Chern Numbers in Three-Terminal Josephson Junctions.
AB - Recently, it has been predicted that the Andreev bound state spectrum of four
terminal Josephson junctions may possess zero-energy Weyl singularities. Using
one superconducting phase as a control parameter, these singularities are
associated with topological transitions between time-reversal symmetry broken
phases with different Chern numbers. Here we show that such topological
transitions may also be tuned with a magnetic flux through the junction area in a
three-terminal geometry.
PMID- 29341693
TI - Erratum: Evidence for a Phase Transition in Silicate Melt at Extreme Pressure and
Temperature Conditions [Phys. Rev. Lett. 108, 065701 (2012)].
AB - This corrects the article DOI: 10.1103/PhysRevLett.108.065701.
PMID- 29341694
TI - Publisher's Note: Solar Irradiance Variability is Caused by the Magnetic Activity
on the Solar Surface [Phys. Rev. Lett. 119, 091102 (2017)].
AB - This corrects the article DOI: 10.1103/PhysRevLett.119.091102.
PMID- 29341695
TI - Scaling of Majorana Zero-Bias Conductance Peaks.
AB - We report an experimental study of the scaling of zero-bias conductance peaks
compatible with Majorana zero modes as a function of magnetic field, tunnel
coupling, and temperature in one-dimensional structures fabricated from an
epitaxial semiconductor-superconductor heterostructure. Results are consistent
with theory, including a peak conductance that is proportional to tunnel
coupling, saturates at 2e^{2}/h, decreases as expected with field-dependent gap,
and collapses onto a simple scaling function in the dimensionless ratio of
temperature and tunnel coupling.
PMID- 29341696
TI - Coherent Beam-Beam Instability in Collisions with a Large Crossing Angle.
AB - In recent years the "crab-waist collision" scheme [P. Raimondi, Proceedings of
2nd SuperB Workshop, Frascati, 2006.; M. Zobov et al., Phys. Rev. Lett. 104,
174801 (2010)PRLTAO0031-900710.1103/PhysRevLett.104.174801] has become popular
for circular e^{+} e^{-} colliders. The designs of several future colliders are
based on this scheme. So far the beam-beam effects for collisions under a large
crossing angle with or without crab waist were mostly studied using weak-strong
simulations. We present here strong-strong simulations showing a novel strong
coherent head-tail instability, which can limit the performance of proposed
future colliders. We explain the underlying instability mechanism starting from
the "cross-wake force" induced by the beam-beam interaction. Using this beam-beam
wake, the beam-beam head tail modes are studied by an eigenmode analysis. The
instability may affect all collider designs based on the crab-waist scheme. We
suggest an experimental verification at SuperKEKB during its commissioning phase
II.
PMID- 29341697
TI - Large-Scale Structure and Hyperuniformity of Amorphous Ices.
AB - We investigate the large-scale structure of amorphous ices and transitions
between their different forms by quantifying their large-scale density
fluctuations. Specifically, we simulate the isothermal compression of low-density
amorphous ice (LDA) and hexagonal ice to produce high-density amorphous ice
(HDA). Both HDA and LDA are nearly hyperuniform; i.e., they are characterized by
an anomalous suppression of large-scale density fluctuations. By contrast, in
correspondence with the nonequilibrium phase transitions to HDA, the presence of
structural heterogeneities strongly suppresses the hyperuniformity and the system
becomes hyposurficial (devoid of "surface-area fluctuations"). Our investigation
challenges the largely accepted "frozen-liquid" picture, which views glasses as
structurally arrested liquids. Beyond implications for water, our findings enrich
our understanding of pressure-induced structural transformations in glasses.
PMID- 29341698
TI - General Linearized Theory of Quantum Fluctuations around Arbitrary Limit Cycles.
AB - The theory of Gaussian quantum fluctuations around classical steady states in
nonlinear quantum-optical systems (also known as standard linearization) is a
cornerstone for the analysis of such systems. Its simplicity, together with its
accuracy far from critical points or situations where the nonlinearity reaches
the strong coupling regime, has turned it into a widespread technique, being the
first method of choice in most works on the subject. However, such a technique
finds strong practical and conceptual complications when one tries to apply it to
situations in which the classical long-time solution is time dependent, a most
prominent example being spontaneous limit-cycle formation. Here, we introduce a
linearization scheme adapted to such situations, using the driven Van der Pol
oscillator as a test bed for the method, which allows us to compare it with full
numerical simulations. On a conceptual level, the scheme relies on the connection
between the emergence of limit cycles and the spontaneous breaking of the
symmetry under temporal translations. On the practical side, the method keeps the
simplicity and linear scaling with the size of the problem (number of modes)
characteristic of standard linearization, making it applicable to large (many
body) systems.
PMID- 29341699
TI - Emission of Nonclassical Radiation by Inelastic Cooper Pair Tunneling.
AB - We show that a properly dc-biased Josephson junction in series with two microwave
resonators of different frequencies emits photon pairs in the resonators. By
measuring auto- and intercorrelations of the power leaking out of the resonators,
we demonstrate two-mode amplitude squeezing below the classical limit. This
nonclassical microwave light emission is found to be in quantitative agreement
with our theoretical predictions, up to an emission rate of 2 billion photon
pairs per second.
PMID- 29341700
TI - Optimal Measurements for Simultaneous Quantum Estimation of Multiple Phases.
AB - A quantum theory of multiphase estimation is crucial for quantum-enhanced sensing
and imaging and may link quantum metrology to more complex quantum computation
and communication protocols. In this Letter, we tackle one of the key
difficulties of multiphase estimation: obtaining a measurement which saturates
the fundamental sensitivity bounds. We derive necessary and sufficient conditions
for projective measurements acting on pure states to saturate the ultimate
theoretical bound on precision given by the quantum Fisher information matrix. We
apply our theory to the specific example of interferometric phase estimation
using photon number measurements, a convenient choice in the laboratory. Our
results thus introduce concepts and methods relevant to the future theoretical
and experimental development of multiparameter estimation.
PMID- 29341701
TI - 3D Quantum Hall Effect of Fermi Arcs in Topological Semimetals.
AB - The quantum Hall effect is usually observed in 2D systems. We show that the Fermi
arcs can give rise to a distinctive 3D quantum Hall effect in topological
semimetals. Because of the topological constraint, the Fermi arc at a single
surface has an open Fermi surface, which cannot host the quantum Hall effect. Via
a "wormhole" tunneling assisted by the Weyl nodes, the Fermi arcs at opposite
surfaces can form a complete Fermi loop and support the quantum Hall effect. The
edge states of the Fermi arcs show a unique 3D distribution, giving an example of
(d-2)-dimensional boundary states. This is distinctly different from the surface
state quantum Hall effect from a single surface of topological insulator. As the
Fermi energy sweeps through the Weyl nodes, the sheet Hall conductivity evolves
from the 1/B dependence to quantized plateaus at the Weyl nodes. This behavior
can be realized by tuning gate voltages in a slab of topological semimetal, such
as the TaAs family, Cd_{3}As_{2}, or Na_{3}Bi. This work will be instructive not
only for searching transport signatures of the Fermi arcs but also for exploring
novel electron gases in other topological phases of matter.
PMID- 29341702
TI - Kinetic Energy of a Trapped Fermi Gas at Finite Temperature.
AB - We study the statistics of the kinetic (or, equivalently, potential) energy for N
noninteracting fermions in a 1d harmonic trap of frequency omega at finite
temperature T. Remarkably, we find an exact solution for the full distribution of
the kinetic energy, at any temperature T and for any N, using a nontrivial
mapping to an integrable Calogero-Moser-Sutherland model. As a function of
temperature T and for large N, we identify (i) a quantum regime, for T~homega,
where quantum fluctuations dominate and (ii) a thermal regime, for T~Nhomega,
governed by thermal fluctuations. We show how the mean and the variance as well
as the large deviation function associated with the distribution of the kinetic
energy cross over from the quantum to the thermal regime as T increases.
PMID- 29341703
TI - Negative Landau Damping in Bilayer Graphene.
AB - We theoretically demonstrate that a system formed by two coupled graphene sheets
enables a negative damping regime wherein graphene plasmons are pumped by a
direct current. This effect is triggered by electrons drifting through one of the
graphene sheets and leads to wave instabilities and a spontaneous light emission
(spasing) in the midinfrared range. It is shown that there is a deep link between
the drift-induced instabilities and wave instabilities in moving media, as both
result from the hybridization of oscillators with oppositely signed frequencies.
With a thickness of a few nanometers and wide spectral tunability, the proposed
structure may find interesting applications in nanophotonic circuitry as an on
chip light source.
PMID- 29341704
TI - Anomaly Indicators for Time-Reversal Symmetric Topological Orders.
AB - Some time-reversal symmetric topological orders are anomalous in that they cannot
be realized in strictly two-dimensional systems; instead, they can only be
realized on the surface of three-dimensional symmetry-protected topological
phases. We propose two quantities, which we call anomaly indicators, that can
detect if a time-reversal symmetric topological order is anomalous in this sense.
Both anomaly indicators are expressed in terms of the quantum dimensions,
topological spins, and time-reversal properties of the anyons in the given
topological order. The first indicator, eta_{2}, applies to bosonic systems while
the second indicator, eta_{f}, applies to fermionic systems in the DIII class. We
conjecture that eta_{2}, together with a previously known indicator eta_{1}, can
detect the two known Z_{2} anomalies in the bosonic case, while eta_{f} can
detect the Z_{16} anomaly in the fermionic case.
PMID- 29341705
TI - Electromagnetic Charge Radius of the Pion at High Precision.
AB - We present a determination of the pion charge radius from high precision data on
the pion vector form factor from both timelike and spacelike regions, using a
novel formalism based on analyticity and unitarity. At low energies, instead of
the poorly known modulus of the form factor, we use its phase, known with high
accuracy from Roy equations for pipi elastic scattering via the Fermi-Watson
theorem. We use also the values of the modulus at several higher timelike
energies, where the data from e^{+}e^{-} annihilation and tau decay are mutually
consistent, as well as the most recent measurements at spacelike momenta. The
experimental uncertainties are implemented by Monte Carlo simulations. The
results, which do not rely on a specific parametrization, are optimal for the
given input information and do not depend on the unknown phase of the form factor
above the first inelastic threshold. Our prediction for the charge radius of the
pion is r_{pi}=(0.657+/-0.003) fm, which amounts to an increase in precision by
a factor of about 2.7 compared to the Particle Data Group average.
PMID- 29341706
TI - Optical Force Enhancement Using an Imaginary Vector Potential for Photons.
AB - The enhancement of optical forces has enabled a variety of technological
applications that rely on the optical control of small objects and devices.
Unfortunately, optical forces are still too small for the convenient actuation of
integrated switches and waveguide couplers. Here we show how the optical gradient
force can be enhanced by an order of magnitude by making use of gauge materials
inside two evanescently coupled waveguides. To this end, the gauge materials
inside the cores should emulate imaginary vector potentials for photons pointing
perpendicularly to the waveguide plane. Depending on the relative orientation of
the vector potentials in neighboring waveguides, i.e., pointing away from or
towards each other, the conventional attractive force due to an even mode profile
may be enhanced, suppressed, or may even become repulsive. This and other new
features indicate that the implementation of complex-valued vector potentials
with non-Hermitian waveguide cores may further enhance our control over mode
profiles and the associated optical forces.
PMID- 29341707
TI - Anomalous Acoustic Plasmon Mode from Topologically Protected States.
AB - Plasmons, the collective excitations of electrons in the bulk or at the surface,
play an important role in the properties of materials, and have generated the
field of "plasmonics." We report the observation of a highly unusual acoustic
plasmon mode on the surface of a three-dimensional topological insulator (TI)
Bi_{2}Se_{3}, using momentum resolved inelastic electron scattering. In sharp
contrast to ordinary plasmon modes, this mode exhibits almost linear dispersion
into the second Brillouin zone and remains prominent with remarkably weak damping
not seen in any other systems. This behavior must be associated with the inherent
robustness of the electrons in the TI surface state, so that not only the surface
Dirac states but also their collective excitations are topologically protected.
On the other hand, this mode has much smaller energy dispersion than expected
from a continuous media excitation picture, which can be attributed to the strong
coupling with surface phonons.
PMID- 29341708
TI - High-Precision Probe of the Fully Sequential Decay Width of the Hoyle State in
^{12}C.
AB - The decay path of the Hoyle state in ^{12}C (E_{x}=7.654 MeV) has been studied
with the ^{14}N(d,alpha_{2})^{12}C(7.654) reaction induced at 10.5 MeV. High
resolution invariant mass spectroscopy techniques have allowed us to
unambiguously disentangle direct and sequential decays of the state passing
through the ground state of ^{8}Be. Thanks to the almost total absence of
background and the attained resolution, a fully sequential decay contribution to
the width of the state has been observed. The direct decay width is negligible,
with an upper limit of 0.043% (95% C.L.). The precision of this result is about a
factor 5 higher than previous studies. This has significant implications on
nuclear structure, as it provides constraints to 3alpha cluster model
calculations, where higher precision limits are needed.
PMID- 29341709
TI - Probing Primordial Black Hole Dark Matter with Gravitational Waves.
AB - Primordial black holes (PBHs) have long been suggested as a candidate for making
up some or all of the dark matter in the Universe. Most of the theoretically
possible mass range for PBH dark matter has been ruled out with various null
observations of expected signatures of their interaction with standard
astrophysical objects. However, current constraints are significantly less robust
in the 20 M_{?}?M_{PBH}?100 M_{?} mass window, which has received much
attention recently, following the detection of merging black holes with estimated
masses of ~30 M_{?} by LIGO and the suggestion that these could be black holes
formed in the early Universe. We consider the potential of advanced LIGO (aLIGO)
operating at design sensitivity to probe this mass range by looking for peaks in
the mass spectrum of detected events. To quantify the background, which is due to
black holes that are formed from dying stars, we model the shape of the stellar
black-hole mass function and calibrate its amplitude to match the O1 results.
Adopting very conservative assumptions about the PBH and stellar-black-hole
merger rates, we show that ~5 yr of aLIGO data can be used to detect a
contribution of >20 M_{?} PBHs to dark matter down to f_{PBH}<0.5 at >99.9%
confidence level. Combined with other probes that already suggest tension with
f_{PBH}=1, the obtainable independent limits from aLIGO will thus enable a firm
test of the scenario that PBHs make up all of dark matter.
PMID- 29341710
TI - Vibrational Action Spectroscopy of Solids: New Surface-Sensitive Technique.
AB - Vibrational action spectroscopy employing infrared radiation from a free-electron
laser has been successfully used for many years to study the vibrational and
structural properties of gas phase aggregates. Despite the high sensitivity of
this method no relevant studies have yet been conducted for solid sample
surfaces. We have set up an experiment for the application of this method to such
targets, using infrared light from the free-electron laser of the Fritz Haber
Institute. In this Letter, we present first results of this technique with
adsorbed argon and neon atoms as messengers. We were able to detect surface
located vibrations of a thin V_{2}O_{3}(0001) film on Au(111) as well as
adsorbate vibrations, demonstrating that this method is highly surface sensitive.
We consider that the dominant channel for desorption of the messenger atoms is
direct inharmonic vibrational coupling, which is essentially insensitive to
subsurface or bulk vibrations. Another channel is thermal desorption due to
sample heating by absorption of infrared light. The high surface sensitivity of
the nonthermal channel and its insensitivity to subsurface modes makes this
technique an ideal tool for the study of surface-located vibrations.
PMID- 29341711
TI - Macroscopic Polarization from Antiferrodistortive Cycloids in Ferroelastic
SrTiO_{3}.
AB - Based on a first-principles based multiscale approach, we study the polarity P of
ferroelastic twin walls in SrTiO_{3}. In addition to flexoelectricity, which was
pointed out before, we identify two new mechanisms that crucially contribute to
P: a direct "rotopolar" coupling to the gradients of the antiferrodistortive
oxygen tilts, and a trilinear coupling that is mediated by the antiferroelectric
displacement of the Ti atoms. Remarkably, the rotopolar coupling presents a
strong analogy to the mechanism that generates a spontaneous polarization in
cycloidal magnets. We show how this similarity allows for a breakdown of
macroscopic inversion symmetry (and therefore a macroscopic polarization) in a
periodic sequence of parallel twins. These results open new avenues towards
engineering pyroelectricity or piezoelectricity in nominally nonpolar ferroic
materials.
PMID- 29341712
TI - Spatial Multiplexing of Atom-Photon Entanglement Sources using Feedforward
Control and Switching Networks.
AB - The light-matter quantum interface that can create quantum correlations or
entanglement between a photon and one atomic collective excitation is a
fundamental building block for a quantum repeater. The intrinsic limit is that
the probability of preparing such nonclassical atom-photon correlations has to be
kept low in order to suppress multiexcitation. To enhance this probability
without introducing multiexcitation errors, a promising scheme is to apply
multimode memories to the interface. Significant progress has been made in
temporal, spectral, and spatial multiplexing memories, but the enhanced
probability for generating the entangled atom-photon pair has not been
experimentally realized. Here, by using six spin-wave-photon entanglement
sources, a switching network, and feedforward control, we build a multiplexed
light-matter interface and then demonstrate a ~sixfold (~fourfold) probability
increase in generating entangled atom-photon (photon-photon) pairs. The measured
compositive Bell parameter for the multiplexed interface is 2.49+/-0.03 combined
with a memory lifetime of up to ~51 MUs.
PMID- 29341713
TI - Field-Induced Instability of a Gapless Spin Liquid with a Spinon Fermi Surface.
AB - The ground state of the quantum kagome antiferromagnet Zn-brochantite,
ZnCu_{3}(OH)_{6}SO_{4}, which is one of only a few known spin-liquid (SL)
realizations in two or three dimensions, has been described as a gapless SL with
a spinon Fermi surface. Employing nuclear magnetic resonance in a broad magnetic
field range down to millikelvin temperatures, we show that in applied magnetic
fields this enigmatic state is intrinsically unstable against a SL with a full or
a partial gap. A similar instability of the gapless Fermi-surface SL was
previously encountered in an organic triangular-lattice antiferromagnet,
suggesting a common destabilization mechanism that most likely arises from spinon
pairing. A salient property of this instability is that an infinitesimal field
suffices to induce it, as predicted theoretically for some other types of gapless
SLs.
PMID- 29341714
TI - Kinetically Controlled Two-Step Amorphization and Amorphous-Amorphous Transition
in Ice.
AB - We report the results of in situ structural characterization of the amorphization
of crystalline ice Ih under compression and the relaxation of high-density
amorphous (HDA) ice under decompression at temperatures between 96 and 160 K by
synchrotron x-ray diffraction. The results show that ice Ih transforms to an
intermediate crystalline phase at 100 K prior to complete amorphization, which is
supported by molecular dynamics calculations. The phase transition pathways show
clear temperature dependence: direct amorphization without an intermediate phase
is observed at 133 K, while at 145 K a direct Ih-to-IX transformation is
observed; decompression of HDA shows a transition to low-density amorphous ice at
96 K and ~1 Pa, to ice Ic at 135 K and to ice IX at 145 K. These observations
show that the amorphization of compressed ice Ih and the recrystallization of
decompressed HDA are strongly dependent on temperature and controlled by kinetic
barriers. Pressure-induced amorphous ice is an intermediate state in the phase
transition from the connected H-bond water network in low pressure ices to the
independent and interpenetrating H-bond network of high-pressure ices.
PMID- 29341715
TI - Potential Energy Surface Reconstruction and Lifetime Determination of Molecular
Double-Core-Hole States in the Hard X-Ray Regime.
AB - A combination of resonant inelastic x-ray scattering and resonant Auger
spectroscopy provides complementary information on the dynamic response of
resonantly excited molecules. This is exemplified for CH_{3}I, for which we
reconstruct the potential energy surface of the dissociative I 3d^{-2} double
core-hole state and determine its lifetime. The proposed method holds a strong
potential for monitoring the hard x-ray induced electron and nuclear dynamic
response of core-excited molecules containing heavy elements, where ab initio
calculations of potential energy surfaces and lifetimes remain challenging.
PMID- 29341716
TI - Single-Electron and Single-Photon Sensitivity with a Silicon Skipper CCD.
AB - We have developed ultralow-noise electronics in combination with repetitive,
nondestructive readout of a thick, fully depleted charge-coupled device (CCD) to
achieve an unprecedented noise level of 0.068 e^{-} rms/pixel. This is the first
time that discrete subelectron readout noise has been achieved reproducible over
millions of pixels on a stable, large-area detector. This enables the
contemporaneous, discrete, and quantized measurement of charge in pixels,
irrespective of whether they contain zero electrons or thousands of electrons.
Thus, the resulting CCD detector is an ultra-sensitive calorimeter. It is also
capable of counting single photons in the optical and near-infrared regime.
Implementing this innovative non-destructive readout system has a negligible
impact on CCD design and fabrication, and there are nearly immediate scientific
applications. As a particle detector, this CCD will have unprecedented
sensitivity to low-mass dark matter particles and coherent neutrino-nucleus
scattering, while future astronomical applications may include direct imaging and
spectroscopy of exoplanets.
PMID- 29341717
TI - Magnetic Circular Dichroism in X-Ray Emission from Ferromagnets.
AB - The existence of novel magnetic circular dichroism in core-level x-ray emission
is reported. By means of circular polarization analysis, the dichroic effect of
the Fe Kalpha_{1} emission spectrum is measured on an Fe single crystal. The
observed dichroic effect (12%) is remarkably large, if one takes into account the
small dichroic effect (about 0.5%) in the conventional K-edge absorption
spectroscopy of 3d transition metal elements. The mechanism is ascribed to
exchange splitting of the 2p level possessing large spin-orbit coupling. This new
magnetooptical effect enables us to explore a variety of new research subjects in
the magnetism of 3d transition metals and their compounds by fully utilizing its
large dichroic effect, the true bulk sensitivity of hard x rays, and the element
selectivity of core-level spectroscopy.
PMID- 29341719
TI - Detecting Topological Invariants in Nonunitary Discrete-Time Quantum Walks.
AB - We report the experimental detection of bulk topological invariants in nonunitary
discrete-time quantum walks with single photons. The nonunitarity of the quantum
dynamics is enforced by periodically performing partial measurements on the
polarization of the walker photon, which effectively introduces loss to the
dynamics. The topological invariant of the nonunitary quantum walk is manifested
in the quantized average displacement of the walker, which is probed by
monitoring the photon loss. We confirm the topological properties of the system
by observing localized edge states at the boundary of regions with different
topological invariants. We further demonstrate the robustness of both the
topological properties and the measurement scheme of the topological invariants
against disorder.
PMID- 29341720
TI - Magnetic Skyrmions and Skyrmion Clusters in the Helical Phase of Cu_{2}OSeO_{3}.
AB - Skyrmions are nanometric spin whirls that can be stabilized in magnets lacking
inversion symmetry. The properties of isolated Skyrmions embedded in a
ferromagnetic background have been intensively studied. We show that single
Skyrmions and clusters of Skyrmions can also form in the helical phase and
investigate theoretically their energetics and dynamics. The helical background
provides natural one-dimensional channels along which a Skyrmion can move
rapidly. In contrast to Skyrmions in ferromagnets, the Skyrmion-Skyrmion
interaction has a strong attractive component and thus Skyrmions tend to form
clusters with characteristic shapes. These clusters are directly observed in
transmission electron microscopy measurements in thin films of Cu_{2}OSeO_{3}.
Topological quantization, high mobility, and the confinement of Skyrmions in
channels provided by the helical background may be useful for future spintronics
devices.
PMID- 29341721
TI - Nonexponential Quantum Decay under Environmental Decoherence.
AB - A system prepared in an unstable quantum state generally decays following an
exponential law, as environmental decoherence is expected to prevent the decay
products from recombining to reconstruct the initial state. Here we show the
existence of deviations from exponential decay in open quantum systems under very
general conditions. Our results are illustrated with the exact dynamics under
quantum Brownian motion and suggest an explanation of recent experimental
observations.
PMID- 29341722
TI - A Laser Excitation Scheme for ^{229m}Th.
AB - Direct laser excitation of the lowest known nuclear excited state in ^{229}Th has
been a long-standing objective. It is generally assumed that reaching this goal
would require a considerably reduced uncertainty of the isomer's excitation
energy compared to the presently adopted value of (7.8+/-0.5) eV. Here we
present a direct laser excitation scheme for ^{229m}Th, which circumvents this
requirement. The proposed excitation scheme makes use of already existing laser
technology and therefore paves the way for nuclear laser spectroscopy. In this
concept, the recently experimentally observed internal-conversion decay channel
of the isomeric state is used for probing the isomeric population. A signal-to
background ratio of better than 10^{4} and a total measurement time of less than
three days for laser scanning appear to be achievable.
PMID- 29341723
TI - Improving a Solid-State Qubit through an Engineered Mesoscopic Environment.
AB - A controlled quantum system can alter its environment by feedback, leading to
reduced-entropy states of the environment and to improved system coherence. Here,
using a quantum-dot electron spin as a control and probe, we prepare the quantum
dot nuclei under the feedback of coherent population trapping and observe their
evolution from a thermal to a reduced-entropy state, with the immediate
consequence of extended qubit coherence. Via Ramsey interferometry on the
electron spin, we directly access the nuclear distribution following its
preparation and measure the emergence and decay of correlations within the
nuclear ensemble. Under optimal feedback, the inhomogeneous dephasing time of the
electron, T_{2}^{*}, is extended by an order of magnitude to 39 ns. Our results
can be readily exploited in quantum information protocols utilizing spin-photon
entanglement and represent a step towards creating quantum many-body states in a
mesoscopic nuclear-spin ensemble.
PMID- 29341724
TI - Landau Damping of Beam Instabilities by Electron Lenses.
AB - Modern and future particle accelerators employ increasingly higher intensity and
brighter beams of charged particles and become operationally limited by coherent
beam instabilities. Usual methods to control the instabilities, such as octupole
magnets, beam feedback dampers, and use of chromatic effects, become less
effective and insufficient. We show that, in contrast, Lorentz forces of a low
energy, magnetically stabilized electron beam, or "electron lens," easily
introduce transverse nonlinear focusing sufficient for Landau damping of
transverse beam instabilities in accelerators. It is also important to note that,
unlike other nonlinear elements, the electron lens provides the frequency spread
mainly at the beam core, thus allowing much higher frequency spread without
lifetime degradation. For the parameters of the Future Circular Collider, a
single conventional electron lens a few meters long would provide stabilization
superior to tens of thousands of superconducting octupole magnets.
PMID- 29341725
TI - New Measurement of the Direct 3alpha Decay from the ^{12}C Hoyle State.
AB - Excited states in certain atomic nuclei possess an unusual structure, where the
dominant degrees of freedom are those of alpha clusters rather than individual
nucleons. It has been proposed that the diffuse 3alpha system of the ^{12}C Hoyle
state may behave like a Bose-Einstein condensate, where the alpha clusters
maintain their bosonic identities. By measuring the decay of the Hoyle state into
three alpha particles, we obtained an upper limit for the rare direct 3alpha
decay branch of 0.047%. This value is now at a level comparable with theoretical
predictions and could be a sensitive probe of the structure of this state.
PMID- 29341726
TI - Exposing the QCD Splitting Function with CMS Open Data.
AB - The splitting function is a universal property of quantum chromodynamics (QCD)
which describes how energy is shared between partons. Despite its ubiquitous
appearance in many QCD calculations, the splitting function cannot be measured
directly, since it always appears multiplied by a collinear singularity factor.
Recently, however, a new jet substructure observable was introduced which
asymptotes to the splitting function for sufficiently high jet energies. This
provides a way to expose the splitting function through jet substructure
measurements at the Large Hadron Collider. In this Letter, we use public data
released by the CMS experiment to study the two-prong substructure of jets and
test the 1->2 splitting function of QCD. To our knowledge, this is the first ever
physics analysis based on the CMS Open Data.
PMID- 29341727
TI - Charge Density Waves in Graphite: Towards the Magnetic Ultraquantum Limit.
AB - Graphite is a model system for the study of three-dimensional electrons and holes
in the magnetic quantum limit, in which the charges are confined to the lowest
Landau levels. We report magneto-transport measurements in pulsed magnetic fields
up to 60 T, which resolve the collapse of two charge density wave states in two,
electron and hole, Landau levels at 52.3 and 54.2 T, respectively. We report
evidence for a commensurate charge density wave at 47.1 T in the electron Landau
level, and discuss the likely nature of the density wave instabilities over the
full field range. The theoretical modeling of our results predicts that the
ultraquantum limit is entered above 73.5 T. This state is an insulator, and we
discuss its correspondence to the "metallic" state reported earlier. We propose
that this (interaction-induced) insulating phase supports surface states that
carry no charge or spin within the planes, but does, however, support charge
transport out of plane.
PMID- 29341728
TI - Multislip Friction with a Single Ion.
AB - A trapped ion transported along a periodic potential is studied as a paradigmatic
nanocontact frictional interface. The combination of the periodic corrugation
potential and a harmonic trapping potential creates a one-dimensional energy
landscape with multiple local minima, corresponding to multistable stick-slip
friction. We measure the probabilities of slipping to the various minima for
various corrugations and transport velocities. The observed probabilities show
that the multislip regime can be reached dynamically at smaller corrugations than
would be possible statically, and can be described by an equilibrium Boltzmann
model. While a clear microscopic signature of multislip behavior is observed for
the ion motion, the frictional force and dissipation are only weakly affected by
the transition to multistable potentials.
PMID- 29341729
TI - Printing Non-Euclidean Solids.
AB - Geometrically frustrated solids with a non-Euclidean reference metric are
ubiquitous in biology and are becoming increasingly relevant in technological
applications. Often they acquire a targeted configuration of incompatibility
through the surface accretion of mass as in tree growth or dam construction. We
use the mechanics of incompatible surface growth to show that geometrical
frustration developing during deposition can be fine-tuned to ensure a particular
behavior of the system in physiological (or working) conditions. As an
illustration, we obtain an explicit 3D printing protocol for arteries, which
guarantees stress uniformity under inhomogeneous loading, and for explosive
plants, allowing a complete release of residual elastic energy with a single cut.
Interestingly, in both cases reaching the physiological target requires the
incompatibility to have a topological (global) component.
PMID- 29341718
TI - Search for Invisible Decays of a Dark Photon Produced in e^{+}e^{-} Collisions at
BaBar.
AB - We search for single-photon events in 53 fb^{-1} of e^{+}e^{-} collision data
collected with the BABAR detector at the PEP-II B-Factory. We look for events
with a single high-energy photon and a large missing momentum and energy,
consistent with production of a spin-1 particle A^{'} through the process
e^{+}e^{-}->gammaA^{'}; A^{'}->invisible. Such particles, referred to as "dark
photons," are motivated by theories applying a U(1) gauge symmetry to dark
matter. We find no evidence for such processes and set 90% confidence level upper
limits on the coupling strength of A^{'} to e^{+}e^{-} in the mass range
m_{A^{'}}<=8 GeV. In particular, our limits exclude the values of the A^{'}
coupling suggested by the dark-photon interpretation of the muon (g-2)_{MU}
anomaly, as well as a broad range of parameters for the dark-sector models.
PMID- 29341730
TI - Polymer Chain Conformation and Dynamical Confinement in a Model One-Component
Nanocomposite.
AB - We report a neutron-scattering investigation on the structure and dynamics of a
single-component nanocomposite based on SiO_{2} particles that were grafted with
polyisoprene chains at the entanglement limit. By skillful labeling, we access
both the monomer density in the corona as well as the conformation of the grafted
chains. While the corona profile follows a r^{-1} power law, the conformation of
a grafted chain is identical to that of a chain in a reference melt, implying a
high mutual penetration of the coronas from different particles. The brush
crowding leads to topological confinement of the chain dynamics: (i) At local
scales, the segmental dynamics is unchanged compared to the reference melt, while
(ii) at the scale of the chain, the dynamics appears to be slowed down; (iii) by
performing a mode analysis in terms of end-fixed Rouse chains, the slower
dynamics is tracked to topological confinement within the cone spanned by the
adjacent grafts; (iv) by adding 50% matrix chains, the topological confinement
sensed by the grafted chain is lifted partially and the apparent chain motion is
accelerated. We observe a crossover from pure Rouse motion at short times to
topological confined motion beyond the time when the segmental mean squared
displacement has reached the distance to the next graft.
PMID- 29341731
TI - Ultrafocused Electromagnetic Field Pulses with a Hollow Cylindrical Waveguide.
AB - We theoretically show that a dipole externally driven by a pulse with a lower
bounded temporal width, and placed inside a cylindrical hollow waveguide, can
generate a train of arbitrarily short and focused electromagnetic pulses. The
waveguide encloses vacuum with perfect electric conducting walls. A dipole driven
by a single short pulse, which is properly engineered to exploit the linear
spectral filtering of the cylindrical hollow waveguide, excites longitudinal
waveguide modes that are coherently refocused at some particular instances of
time, thereby producing arbitrarily short and focused electromagnetic pulses. We
numerically show that such ultrafocused pulses persist outside the cylindrical
waveguide at distances comparable to its radius.
PMID- 29341732
TI - 3D Sisyphus Cooling of Trapped Ions.
AB - Using a laser polarization gradient, we realize 3D Sisyphus cooling of
^{171}Yb^{+} ions confined in and near the Lamb-Dicke regime in a linear Paul
trap. The cooling rate and final mean motional energy of a single ion are
characterized as a function of laser intensity and compared to semiclassical and
quantum simulations. Sisyphus cooling is also applied to a linear string of four
ions to obtain a mean energy of 1-3 quanta for all vibrational modes, an
approximately order of magnitude reduction below Doppler cooled energies. This is
used to enable subsequent, efficient sideband laser cooling.
PMID- 29341733
TI - Breaking the Temporal Resolution Limit by Superoscillating Optical Beats.
AB - Band-limited functions can oscillate locally at an arbitrarily fast rate through
an interference phenomenon known as superoscillations. Using an optical pulse
with a superoscillatory envelope we experimentally break the temporal Fourier
transform focusing limit with a temporal feature that is approximately three
times shorter than the duration of a transform-limited Gaussian pulse having a
comparable bandwidth while maintaining 30% visibility. We experimentally
demonstrate the ability of such signals to achieve temporal superresolution and
show numerically in which cases such pulses can outperform transform-limited
pulses.
PMID- 29341734
TI - Vapor-Induced Motion of Liquid Droplets on an Inert Substrate.
AB - Evaporating droplets are known to show complex motion that has conventionally
been explained by the Marangoni effect (flow induced by the gradient of surface
tension). Here, we show that the droplet motion can be induced even in the
absence of the Marangoni effect due to the gradient of the evaporation rate. We
derive an equation for the velocity of a droplet subject to the nonuniform
evaporation rate and nonuniform surface tension placed on an inert substrate,
where the wettability is uniform and unchanged. The equation explains the
previously observed attraction-repulsion-chasing behaviors of evaporating
droplets.
PMID- 29341735
TI - Complementarity and Polarization Modulation in Photon Interference.
AB - We derive two general complementarity relations for the distinguishability and
visibility of genuine vector-light quantum fields in double-pinhole photon
interference involving polarization modulation. The established framework reveals
an intrinsic aspect of wave-particle duality of the photon, not previously
reported, thus providing deeper insights into foundational quantum interference
physics.
PMID- 29341736
TI - Emergence of Multiscaling in a Random-Force Stirred Fluid.
AB - We consider the transition to strong turbulence in an infinite fluid stirred by a
Gaussian random force. The transition is defined as a first appearance of
anomalous scaling of normalized moments of velocity derivatives (dissipation
rates) emerging from the low-Reynolds-number Gaussian background. It is shown
that, due to multiscaling, strongly intermittent rare events can be
quantitatively described in terms of an infinite number of different "Reynolds
numbers" reflecting a multitude of anomalous scaling exponents. The theoretically
predicted transition disappears at R_{lambda}<=3. The developed theory is in
quantitative agreement with the outcome of large-scale numerical simulations.
PMID- 29341737
TI - Superradiant Instability and Backreaction of Massive Vector Fields around Kerr
Black Holes.
AB - We study the growth and saturation of the superradiant instability of a complex,
massive vector (Proca) field as it extracts energy and angular momentum from a
spinning black hole, using numerical solutions of the full Einstein-Proca
equations. We concentrate on a rapidly spinning black hole (a=0.99) and the
dominant m=1 azimuthal mode of the Proca field, with real and imaginary
components of the field chosen to yield an axisymmetric stress-energy tensor and,
hence, spacetime. We find that in excess of 9% of the black hole's mass can be
transferred into the field. In all cases studied, the superradiant instability
smoothly saturates when the black hole's horizon frequency decreases to match the
frequency of the Proca cloud that spontaneously forms around the black hole.
PMID- 29341738
TI - Hierarchy Construction and Non-Abelian Families of Generic Topological Orders.
AB - We generalize the hierarchy construction to generic 2+1D topological orders
(which can be non-Abelian) by condensing Abelian anyons in one topological order
to construct a new one. We show that such construction is reversible and leads to
a new equivalence relation between topological orders. We refer to the
corresponding equivalence class (the orbit of the hierarchy construction) as "the
non-Abelian family." Each non-Abelian family has one or a few root topological
orders with the smallest number of anyon types. All the Abelian topological
orders belong to the trivial non-Abelian family whose root is the trivial
topological order. We show that Abelian anyons in root topological orders must be
bosons or fermions with trivial mutual statistics between them. The
classification of topological orders is then greatly simplified, by focusing on
the roots of each family: those roots are given by non-Abelian modular extensions
of representation categories of Abelian groups.
PMID- 29341739
TI - Direct Determination of Dynamic Properties of Coulomb and Yukawa Classical One
Component Plasmas.
AB - Dynamic characteristics of strongly coupled classical one-component Coulomb and
Yukawa plasmas are obtained within the nonperturbative model-free moment approach
without any data input from simulations so that the dynamic structure factor
(DSF) satisfies the first three nonvanishing sum rules automatically. The DSF,
dispersion, decay, sound speed, and other characteristics of the collective modes
are determined using exclusively the static structure factor calculated from
various theoretical approaches including the hypernetted chain approximation. A
good quantitative agreement with molecular dynamics simulation data is achieved.
PMID- 29341740
TI - Digital Quantum Simulation of Minimal AdS/CFT.
AB - We propose the digital quantum simulation of a minimal AdS/CFT model in
controllable quantum platforms. We consider the Sachdev-Ye-Kitaev model
describing interacting Majorana fermions with randomly distributed all-to-all
couplings, encoding nonlocal fermionic operators onto qubits to efficiently
implement their dynamics via digital techniques. Moreover, we also give a method
for probing nonequilibrium dynamics and the scrambling of information. Finally,
our approach serves as a protocol for reproducing a simplified low-dimensional
model of quantum gravity in advanced quantum platforms as trapped ions and
superconducting circuits.
PMID- 29341741
TI - Fractional Spin and Josephson Effect in Time-Reversal-Invariant Topological
Superconductors.
AB - Time-reversal-invariant topological superconducting (TRITOPS) wires are known to
host a fractional spin h/4 at their ends. We investigate how this fractional spin
affects the Josephson current in a TRITOPS-quantum dot-TRITOPS Josephson
junction, describing the wire in a model that can be tuned between a topological
and a nontopological phase. We compute the equilibrium Josephson current of the
full model by continuous-time Monte Carlo simulations and interpret the results
within an effective low-energy theory. We show that in the topological phase, the
0-to-pi transition is quenched via formation of a spin singlet from the quantum
dot spin and the fractional spins associated with the two adjacent topological
superconductors.
PMID- 29341742
TI - Measurement of the Electron-Antineutrino Angular Correlation in Neutron beta
Decay.
AB - We report the first result for the electron-antineutrino angular correlation (a
coefficient) in free neutron beta decay from the aCORN experiment. aCORN uses a
novel method in which the a coefficient is proportional to an asymmetry in proton
time of flight for events where the beta electron and recoil proton are detected
in delayed coincidence. Data are presented from a 15 month run at the NIST Center
for Neutron Research. We obtained a=-0.1090+/-0.0030(stat)+/-0.0028(sys), the
most precise measurement of the neutron a coefficient reported to date.
PMID- 29341743
TI - Size-Dependent Localization in Polydisperse Colloidal Glasses.
AB - We have investigated concentrated suspensions of polydisperse hard spheres and
have determined the dynamics and sizes of individual particles using confocal
microscopy. With increasing concentration, the dynamics of the small and large
particles start to differ. The large particles exhibit slower dynamics and
stronger localization. Moreover, as the particle size increases, the local volume
fraction phi_{loc} also increases. In the glass state, the localization length
significantly decreases beyond phi_{loc}~0.67. This suggests a link between local
crowding and dynamical heterogeneities. However dynamical arrest of
subpopulations seems not directly linked to a large value of phi_{loc},
indicating the importance of collective effects.
PMID- 29341744
TI - Dynamical Transition of Collective Motions in Dry Proteins.
AB - Water is widely assumed to be essential for protein dynamics and function. In
particular, the well-documented "dynamical" transition at ~200 K, at which the
protein changes from a rigid, nonfunctional form to a flexible, functional state,
as detected in hydrogenated protein by incoherent neutron scattering, requires
hydration. Here, we report on coherent neutron scattering experiments on
perdeuterated proteins and reveal that a transition occurs in dry proteins at the
same temperature resulting primarily from the collective heavy-atom motions. The
dynamical transition discovered is intrinsic to the energy landscape of dry
proteins.
PMID- 29341745
TI - Born-Oppenheimer Dynamics, Electronic Friction, and the Inclusion of Electron
Electron Interactions.
AB - We present a universal expression for the electronic friction as felt by a set of
classical nuclear degrees of freedom (DOFs) coupled to a manifold of quantum
electronic DOFs; no assumptions are made regarding the nature of the electronic
Hamiltonian and electron-electron repulsions are allowed. Our derivation is based
on a quantum-classical Liouville equation for the coupled electronic-nuclear
motion, followed by an adiabatic approximation whereby electronic transitions are
assumed to equilibrate faster than nuclear movement. The resulting form of
friction is completely general, but does reduce to previously published
expressions for the quadratic Hamiltonian (i.e., Hamiltonians without electronic
correlation). At equilibrium, the second fluctuation-dissipation theorem is
satisfied and the frictional matrix is symmetric. To demonstrate the importance
of electron-electron correlation, we study electronic friction within the
Anderson-Holstein model, where a proper treatment of electron-electron
interactions shows signatures of a Kondo resonance and a mean-field treatment is
completely inadequate.
PMID- 29341746
TI - Is the Dispersion Relation Applicable for Exotic Nuclear Systems? The Abnormal
Threshold Anomaly in the ^{6}He+^{209}Bi System.
AB - The threshold anomaly of the phenomenological potential has been known for a long
time in nuclear reactions at energies around the Coulomb barrier, where the
connection between the real and imaginary potentials is well described by the
dispersion relation. However, this connection is not clear yet for some weakly
bound nuclear systems, especially for reactions induced by exotic radioactive
nuclei. In this study, precise optical potentials of the halo nuclear system
^{6}He+^{209}Bi were extracted via ^{208}Pb(^{7}Li,^{6}He) transfer reactions
with energies measured downward to the extremely sub-barrier region. The real
potential presents a bell-like shape around the barrier as a normal threshold
anomaly in tightly bound nuclear systems. However, the imaginary potential shows
an abnormal behavior: it increases first with energy decreasing below the barrier
and then falls quickly down to 0. It is the first time the threshold of the
imaginary potential has been determined in an exotic nuclear system. Moreover,
experimental results show the dispersion relation is not applicable for this
system, which may be a common phenomenon for exotic nuclear systems. We discuss
possible explanations for such a peculiar behavior, but further study is still
desired for the underlying physics.
PMID- 29341747
TI - (3+1)D Quasiparticle Anisotropic Hydrodynamics for Ultrarelativistic Heavy-Ion
Collisions.
AB - We present the first comparisons of experimental data with phenomenological
results from (3+1)D quasiparticle anisotropic hydrodynamics (aHydroQP). We
compare particle spectra, average transverse momentum, and elliptic flow. The
dynamical equations used for the hydrodynamic stage utilize aHydroQP, which
naturally includes both shear and bulk viscous effects. The (3+1)D aHydroQP
evolution obtained is self-consistently converted to hadrons using anisotropic
Cooper-Frye freeze-out. Hadron production and decays are modeled using a
customized version of therminator 2. In this first study, we utilized smooth
Glauber-type initial conditions and a single effective freeze-out temperature
T_{FO}=130 MeV with all hadronic species in full chemical equilibrium. With this
rather simple setup, we find a very good description of many heavy-ion
observables.
PMID- 29341748
TI - Sliced Basis Density Matrix Renormalization Group for Electronic Structure.
AB - We introduce a hybrid approach to applying the density matrix renormalization
group to continuous systems, combining a grid approximation along one direction
with a finite Gaussian basis set for the remaining two directions. This approach
is especially useful for chainlike molecules, where the grid is used in the long
direction. For hydrogen chain systems, the computational time scales
approximately linearly with the number of atoms, as we show with near-exact
minimal basis set calculations with up to 1000 atoms. The linear scaling comes
from both the localization of the basis and a compression method for the long
ranged two-electron interaction. For shorter hydrogen chains, we show results
with up to triple-zeta bases.
PMID- 29341749
TI - Towards Attosecond High-Energy Electron Bunches: Controlling Self-Injection in
Laser-Wakefield Accelerators Through Plasma-Density Modulation.
AB - Self-injection in a laser-plasma wakefield accelerator is usually achieved by
increasing the laser intensity until the threshold for injection is exceeded.
Alternatively, the velocity of the bubble accelerating structure can be
controlled using plasma density ramps, reducing the electron velocity required
for injection. We present a model describing self-injection in the short-bunch
regime for arbitrary changes in the plasma density. We derive the threshold
condition for injection due to a plasma density gradient, which is confirmed
using particle-in-cell simulations that demonstrate injection of subfemtosecond
bunches. It is shown that the bunch charge, bunch length, and separation of
bunches in a bunch train can be controlled by tailoring the plasma density
profile.
PMID- 29341750
TI - In-Plane Propagation of Light in Transition Metal Dichalcogenide Monolayers:
Optical Selection Rules.
AB - The optical selection rules for interband transitions in WSe_{2}, WS_{2}, and
MoSe_{2} transition metal dichalcogenide monolayers are investigated by
polarization-resolved photoluminescence experiments with a signal collection from
the sample edge. These measurements reveal a strong polarization dependence of
the emission lines. We see clear signatures of the emitted light with the
electric field oriented perpendicular to the monolayer plane, corresponding to an
interband optical transition forbidden at normal incidence used in standard
optical spectroscopy measurements. The experimental results are in agreement with
the optical selection rules deduced from group theory analysis, highlighting the
key role played by the different symmetries of the conduction and valence bands
split by the spin-orbit interaction. These studies yield a direct determination
of the bright-dark exciton splitting, for which we measure 40+/-1 meV and 55+/-2
meV in WSe_{2} and WS_{2} monolayer, respectively.
PMID- 29341751
TI - Entanglement in Nonunitary Quantum Critical Spin Chains.
AB - Entanglement entropy has proven invaluable to our understanding of quantum
criticality. It is natural to try to extend the concept to "nonunitary quantum
mechanics," which has seen growing interest from areas as diverse as open quantum
systems, noninteracting electronic disordered systems, or nonunitary conformal
field theory (CFT). We propose and investigate such an extension here, by
focusing on the case of one-dimensional quantum group symmetric or supergroup
symmetric spin chains. We show that the consideration of left and right
eigenstates combined with appropriate definitions of the trace leads to a natural
definition of Renyi entropies in a large variety of models. We interpret this
definition geometrically in terms of related loop models and calculate the
corresponding scaling in the conformal case. This allows us to distinguish the
role of the central charge and effective central charge in rational minimal
models of CFT, and to define an effective central charge in other, less well
understood cases. The example of the sl(2|1) alternating spin chain for
percolation is discussed in detail.
PMID- 29341752
TI - Tensor-Network Simulations of the Surface Code under Realistic Noise.
AB - The surface code is a many-body quantum system, and simulating it in generic
conditions is computationally hard. While the surface code is believed to have a
high threshold, the numerical simulations used to establish this threshold are
based on simplified noise models. We present a tensor-network algorithm for
simulating error correction with the surface code under arbitrary local noise. We
use this algorithm to study the threshold and the subthreshold behavior of the
amplitude damping and systematic rotation channels. We also compare these results
to those obtained by making standard approximations to the noise models.
PMID- 29341753
TI - Probing the Nano-Skyrmion Lattice on Fe/Ir(111) with Magnetic Exchange Force
Microscopy.
AB - We demonstrate that the magnetic nano-Skyrmion lattice on the Fe monolayer on
Ir(111) and the positions of the Fe atoms can be resolved simultaneously using
magnetic exchange force microscopy. Thus, the relation between magnetic and
atomic structure can be determined straightforwardly by evaluating the Fourier
transformation of the real space image data. We further show that the magnetic
contrast can be mapped on a Heisenberg-like magnetic interaction between tip and
sample spins. Since our imaging technique is based on measuring forces, our
observation paves the way to study Skyrmions or other complex spin textures on
insulating sample systems with atomic resolution.
PMID- 29341754
TI - Plasma versus Drude Modeling of the Casimir Force: Beyond the Proximity Force
Approximation.
AB - We calculate the Casimir force and its gradient between a spherical and a planar
gold surface. Significant numerical improvements allow us to extend the range of
accessible parameters into the experimental regime. We compare our numerically
exact results with those obtained within the proximity force approximation (PFA)
employed in the analysis of all Casimir force experiments reported in the
literature so far. Special attention is paid to the difference between the Drude
model and the dissipationless plasma model at zero frequency. It is found that
the correction to PFA is too small to explain the discrepancy between the
experimental data and the PFA result based on the Drude model. However, it turns
out that for the plasma model, the corrections to PFA lie well outside the
experimental bound obtained by probing the variation of the force gradient with
the sphere radius [D. E. Krause et al., Phys. Rev. Lett. 98, 050403
(2007)PRLTAO0031-900710.1103/PhysRevLett.98.050403]. The corresponding
corrections based on the Drude model are significantly smaller but still in
violation of the experimental bound for small distances between plane and sphere.
PMID- 29341755
TI - Excitation and Control of Plasma Wakefields by Multiple Laser Pulses.
AB - We demonstrate experimentally the resonant excitation of plasma waves by trains
of laser pulses. We also take an important first step to achieving an energy
recovery plasma accelerator by showing that a plasma wave can be damped by an out
of-resonance trailing laser pulse. The measured laser wakefields are found to be
in excellent agreement with analytical and numerical models of wakefield
excitation in the linear regime. Our results indicate a promising direction for
achieving highly controlled, GeV-scale laser-plasma accelerators operating at
multikilohertz repetition rates.
PMID- 29341756
TI - Generic Theory for Majorana Zero Modes in 2D Superconductors.
AB - It is well known that non-Abelian Majorana zero modes (MZM) are located at vortex
cores in a p_{x}+??p_{y} topological superconductor, which can be realized in a
2D spin-orbit coupled system with a single Fermi surface and by proximity
coupling to an s-wave superconductor. Here we show that the existence of non
Abelian MZMs is unrelated to the bulk topology of a 2D superconductor, and
propose that such exotic modes can result in a much broader range of
superconductors, being topological or trivial. For a generic 2D system with
multiple Fermi surfaces that is gapped out by superconducting pairings, we show
that at least a single MZM survives if there are only an odd number of Fermi
surfaces of which the corresponding superconducting orders have vortices; such a
MZM is protected by an emergent Chern-Simons invariant, irrespective of the bulk
topology of the superconductor. This result enriches new experimental schemes for
realizing non-Abelian MZMs. In particular, we propose a minimal scheme to realize
the MZMs in a 2D superconducting Dirac semimetal with trivial bulk topology,
which can be well achieved based on recent cold-atom experiments.
PMID- 29341757
TI - Deconstructing Temperature Gradients across Fluid Interfaces: The Structural
Origin of the Thermal Resistance of Liquid-Vapor Interfaces.
AB - The interfacial thermal resistance determines condensation-evaporation processes
and thermal transport across material-fluid interfaces. Despite its importance in
transport processes, the interfacial structure responsible for the thermal
resistance is still unknown. By combining nonequilibrium molecular dynamics
simulations and interfacial analyses that remove the interfacial thermal
fluctuations we show that the thermal resistance of liquid-vapor interfaces is
connected to a low density fluid layer that is adsorbed at the liquid surface.
This thermal resistance layer (TRL) defines the boundary where the thermal
transport mechanism changes from that of gases (ballistic) to that characteristic
of dense liquids, dominated by frequent particle collisions involving very short
mean free paths. We show that the thermal conductance is proportional to the
number of atoms adsorbed in the TRL, and hence we explain the structural origin
of the thermal resistance in liquid-vapor interfaces.
PMID- 29341758
TI - Nonreciprocal Magnons and Symmetry-Breaking in the Noncentrosymmetric
Antiferromagnet.
AB - Inelastic neutron scattering measurements were performed to study spin dynamics
in the noncentrosymmetric antiferromagnet alpha-Cu_{2}V_{2}O_{7}. For the first
time, nonreciprocal magnons were experimentally measured in an antiferromagnet.
These nonreciprocal magnons are caused by the incompatibility between anisotropic
exchange and antisymmetric Dzyaloshinskii-Moriya interactions, which arise from
broken symmetry, resulting in a collinear ordered state but helical spin
dynamics. The nonreciprocity introduces the difference in the phase velocity of
the counterrotating modes, causing the opposite spontaneous magnonic Faraday
rotation of the left- and right-propagating spin waves. The breaking of spatial
inversion and time reversal symmetry is revealed as a magnetic-field-induced
asymmetric energy shift, which provides a test for the detailed balance relation.
PMID- 29341759
TI - Crossover from Classical to Fermi Liquid Behavior in Dense Plasmas.
AB - We explore the crossover from classical plasma to quantum Fermi liquid behavior
of electrons in dense plasmas. To this end, we analyze the evolution with density
and temperature of the momentum lifetime of a test electron introduced in a dense
electron gas. This allows us (1) to determine the boundaries of the crossover
region in the temperature-density plane and to shed light on the evolution of
scattering properties across it, (2) to quantify the role of the fermionic nature
of electrons on electronic collisions across the crossover region, and (3) to
explain how the concept of the Coulomb logarithm emerges at a high enough
temperature but disappears at a low enough temperature.
PMID- 29341760
TI - Correlated Photon Dynamics in Dissipative Rydberg Media.
AB - Rydberg blockade physics in optically dense atomic media under the conditions of
electromagnetically induced transparency (EIT) leads to strong dissipative
interactions between single photons. We introduce a new approach to analyzing
this challenging many-body problem in the limit of a large optical depth per
blockade radius. In our approach, we separate the single-polariton EIT physics
from Rydberg-Rydberg interactions in a serialized manner while using a hard
sphere model for the latter, thus capturing the dualistic particle-wave nature of
light as it manifests itself in dissipative Rydberg-EIT media. Using this
approach, we analyze the saturation behavior of the transmission through one
dimensional Rydberg-EIT media in the regime of nonperturbative dissipative
interactions relevant to current experiments. Our model is able to capture the
many-body dynamics of bright, coherent pulses through these strongly interacting
media. We compare our model with available experimental data in this regime and
find good agreement. We also analyze a scheme for generating regular trains of
single photons from continuous-wave input and derive its scaling behavior in the
presence of imperfect single-photon EIT.
PMID- 29341761
TI - Superadditivity of the Classical Capacity with Limited Entanglement Assistance.
AB - Finding the optimal encoding strategies can be challenging for communication
using quantum channels, as classical and quantum capacities may be superadditive.
Entanglement assistance can often simplify this task, as the entanglement
assisted classical capacity for any channel is additive, making entanglement
across channel uses unnecessary. If the entanglement assistance is limited, the
picture is much more unclear. Suppose the classical capacity is superadditive,
then the classical capacity with limited entanglement assistance could retain
superadditivity by continuity arguments. If the classical capacity is additive,
it is unknown if superadditivity can still be developed with limited entanglement
assistance. We show this is possible, by providing an example. We construct a
channel for which the classical capacity is additive, but that with limited
entanglement assistance can be superadditive. This shows entanglement plays a
weird role in communication, and we still understand very little about it.
PMID- 29341763
TI - Auxiliary-Field Monte Carlo Method to Tackle Strong Interactions and Frustration
in Lattice Bosons.
AB - We introduce a new numerical technique, the bosonic auxiliary-field Monte Carlo
method, which allows us to calculate the thermal properties of large lattice
boson systems within a systematically improvable semiclassical approach, and
which is virtually applicable to any bosonic model. Our method amounts to a
decomposition of the lattice into clusters, and to an ansatz for the density
matrix of the system in the form of a cluster-separable state-with nonentangled,
yet classically correlated clusters. This approximation eliminates any sign
problem, and can be systematically improved upon by using clusters of growing
size. Extrapolation in the cluster size allows us to reproduce numerically exact
results for the superfluid transition of hard-core bosons on the square lattice,
and to provide a solid quantitative prediction for the superfluid and chiral
transition of hardcore bosons on the frustrated triangular lattice.
PMID- 29341764
TI - Order by Quenched Disorder in the Model Triangular Antiferromagnet
RbFe(MoO_{4})_{2}.
AB - We observe a disappearance of the 1/3 magnetization plateau and a striking change
of the magnetic configuration under a moderate doping of the model triangular
antiferromagnet RbFe(MoO_{4})_{2}. The reason is an effective lifting of
degeneracy of mean-field ground states by a random potential of impurities, which
compensates, in the low-temperature limit, the fluctuation contribution to free
energy. These results provide a direct experimental confirmation of the
fluctuation origin of the ground state in a real frustrated system. The change of
the ground state to a least collinear configuration reveals an effective positive
biquadratic exchange provided by the structural disorder. On heating, doped
samples regain the structure of a pure compound, thus allowing for an
investigation of the remarkable competition between thermal and structural
disorder.
PMID- 29341765
TI - Magnetic Fluctuations, Precursor Phenomena, and Phase Transition in MnSi under a
Magnetic Field.
AB - The reference chiral helimagnet MnSi is the first system where Skyrmion lattice
correlations have been reported. At a zero magnetic field the transition at T_{C}
to the helimagnetic state is of first order. Above T_{C}, in a region dominated
by precursor phenomena, neutron scattering shows the buildup of strong chiral
fluctuating correlations over the surface of a sphere with radius 2pi/l, where l
is the pitch of the helix. It has been suggested that these fluctuating
correlations drive the helical transition to first order following a scenario
proposed by Brazovskii for liquid crystals. We present a comprehensive neutron
scattering study under magnetic fields, which provides evidence that this is not
the case. The sharp first order transition persists for magnetic fields up to 0.4
T whereas the fluctuating correlations weaken and start to concentrate along the
field direction already above 0.2 T. Our results thus disconnect the first order
nature of the transition from the precursor fluctuating correlations. They also
show no indication for a tricritical point, where the first order transition
crosses over to second order with increasing magnetic field. In this light, the
nature of the first order helical transition and the precursor phenomena above
T_{C}, both of general relevance to chiral magnetism, remain an open question.
PMID- 29341766
TI - Noise-Induced Subdiffusion in Strongly Localized Quantum Systems.
AB - We consider the dynamics of strongly localized systems subject to dephasing noise
with arbitrary correlation time. Although noise inevitably induces
delocalization, transport in the noise-induced delocalized phase is subdiffusive
in a parametrically large intermediate-time window. We argue for this
intermediate-time subdiffusive regime both analytically and using numerical
simulations on single-particle localized systems. Furthermore, we show that
normal diffusion is restored in the long-time limit, through processes analogous
to variable-range hopping. With numerical simulations based on Lanczos exact
diagonalization, we demonstrate that our qualitative conclusions are also valid
for interacting systems in the many-body localized phase.
PMID- 29341767
TI - Dynamics of Dwarf Galaxies Disfavor Stellar-Mass Black Holes as Dark Matter.
AB - We study the effects of black hole dark matter on the dynamical evolution of
stars in dwarf galaxies. We find that mass segregation leads to a depletion of
stars in the center of dwarf galaxies and the appearance of a ring in the
projected stellar surface density profile. Using Segue 1 as an example we show
that current observations of the projected surface stellar density rule out at
the 99.9% confidence level the possibility that more than 6% of the dark matter
is composed of black holes with a mass of few tens of solar masses.
PMID- 29341768
TI - Novel Role of Superfluidity in Low-Energy Nuclear Reactions.
AB - We demonstrate, within symmetry unrestricted time-dependent density functional
theory, the existence of new effects in low-energy nuclear reactions which
originate from superfluidity. The dynamics of the pairing field induces solitonic
excitations in the colliding nuclear systems, leading to qualitative changes in
the reaction dynamics. The solitonic excitation prevents collective energy
dissipation and effectively suppresses the fusion cross section. We demonstrate
how the variations of the total kinetic energy of the fragments can be traced
back to the energy stored in the superfluid junction of colliding nuclei. Both
contact time and scattering angle in noncentral collisions are significantly
affected. The modification of the fusion cross section and possibilities for its
experimental detection are discussed.
PMID- 29341769
TI - Defect Structure of Localized Excitons in a WSe_{2} Monolayer.
AB - The atomic and electronic structure of intrinsic defects in a WSe_{2} monolayer
grown on graphite was revealed by low temperature scanning tunneling microscopy
and spectroscopy. Instead of chalcogen vacancies that prevail in other transition
metal dichalcogenide materials, intrinsic defects in WSe_{2} arise surprisingly
from single tungsten vacancies, leading to the hole (p-type) doping. Furthermore,
we found these defects to dominate the excitonic emission of the WSe_{2}
monolayer at low temperature. Our work provided the first atomic-scale
understanding of defect excitons and paved the way toward deciphering the defect
structure of single quantum emitters previously discovered in the WSe_{2}
monolayer.
PMID- 29341771
TI - Quantum Numbers of Recently Discovered Omega_{c}^{0} Baryons from Lattice QCD.
AB - We present the ground and excited state spectra of Omega_{c}^{0} baryons with
spin up to 7/2 from lattice quantum chromodynamics with dynamical quark fields.
Based on our lattice results, we predict the quantum numbers of five
Omega_{c}^{0} baryons, which have recently been observed by the LHCb
Collaboration. Our results strongly indicate that the observed states
Omega_{c}(3000)^{0} and Omega_{c}(3050)^{0} have spin-parity J^{P}=1/2^{-}, the
states Omega_{c}(3066)^{0} and Omega_{c}(3090)^{0} have J^{P}=3/2^{-}, whereas
Omega_{c}(3119)^{0} is possibly a 5/2^{-} state.
PMID- 29341772
TI - Determinant Diagrammatic Monte Carlo Algorithm in the Thermodynamic Limit.
AB - We present a simple trick that allows us to consider the sum of all connected
Feynman diagrams at fixed position of interaction vertices for general fermionic
models, such that the thermodynamic limit can be taken analytically. With our
approach one can achieve superior performance compared to conventional
diagrammatic Monte Carlo algorithm, while rendering the algorithmic part
dramatically simpler. By considering the sum of all connected diagrams at once,
we allow for massive cancellations between different diagrams, greatly reducing
the sign problem. In the end, the computational effort increases only
exponentially with the order of the expansion, which should be contrasted with
the factorial growth of the standard diagrammatic technique. We illustrate the
efficiency of the technique for the two-dimensional Fermi-Hubbard model.
PMID- 29341773
TI - Collective Optomechanical Effects in Cavity Quantum Electrodynamics.
AB - We investigate a cavity quantum electrodynamic effect, where the alignment of two
dimensional freely rotating optical dipoles is driven by their collective
coupling to the cavity field. By exploiting the formal equivalence of a set of
rotating dipoles with a polymer we calculate the partition function of the
coupled light-matter system and demonstrate that it exhibits a second order phase
transition between a bunched state of isotropic orientations and a stretched one
with all the dipoles aligned. Such a transition manifests itself as an intensity
dependent shift of the polariton mode resonance. Our work, lying at the crossroad
between cavity quantum electrodynamics and quantum optomechanics, is a step
forward in the ongoing quest to understand how strong coupling can be exploited
to influence matter internal degrees of freedom.
PMID- 29341774
TI - Tailoring Correlations of the Local Density of States in Disordered Photonic
Materials.
AB - We present experimental evidence for the different mechanisms driving the
fluctuations of the local density of states (LDOS) in disordered photonic
systems. We establish a clear link between the microscopic structure of the
material and the frequency correlation function of LDOS accessed by a near-field
hyperspectral imaging technique. We show, in particular, that short- and long
range frequency correlations of LDOS are controlled by different physical
processes (multiple or single scattering processes, respectively) that can be-to
some extent-manipulated independently. We also demonstrate that the single
scattering contribution to LDOS fluctuations is sensitive to subwavelength
features of the material and, in particular, to the correlation length of its
dielectric function. Our work paves a way towards complete control of statistical
properties of disordered photonic systems, allowing for designing materials with
predefined correlations of LDOS.
PMID- 29341775
TI - Mixing by Unstirring: Hyperuniform Dispersion of Interacting Particles upon
Chaotic Advection.
AB - We show how to achieve both fast and hyperuniform dispersions of particles in
viscous fluids. To do so, we first extend the concept of critical random
organization to chaotic drives. We show how palindromic sequences of chaotic
advection cause microscopic particles to effectively interact at long range,
thereby inhibiting critical self-organization. Based on this understanding we go
around this limitation and design sequences of stirring and unstirring which
simultaneously optimize the speed of particle spreading and the homogeneity of
the resulting dispersions.
PMID- 29341770
TI - Search for Neutrinoless Quadruple-beta Decay of ^{150}Nd with the NEMO-3
Detector.
AB - We report the results of a first experimental search for lepton number violation
by four units in the neutrinoless quadruple-beta decay of ^{150}Nd using a total
exposure of 0.19 kg yr recorded with the NEMO-3 detector at the Modane
Underground Laboratory. We find no evidence of this decay and set lower limits on
the half-life in the range T_{1/2}>(1.1-3.2)*10^{21} yr at the 90% C.L.,
depending on the model used for the kinematic distributions of the emitted
electrons.
PMID- 29341776
TI - Magnetic Domain Walls as Hosts of Spin Superfluids and Generators of Skyrmions.
AB - A domain wall in a magnet with easy-axis anisotropy is shown to harbor spin
superfluid associated with its spontaneous breaking of the U(1) spin-rotational
symmetry. The spin superfluid is shown to have several topological properties,
which are absent in conventional superfluids. First, the associated phase slips
create and destroy Skyrmions to obey the conservation of the total Skyrmion
charge, which allows us to use a domain wall as a generator and detector of
Skyrmions. Second, the domain wall engenders the emergent magnetic flux for
magnons along its length, which are proportional to the spin supercurrent flowing
through it, and thereby provides a way to manipulate magnons. Third, the spin
supercurrent can be driven by the magnon current traveling across it owing to the
spin transfer between the domain wall and magnons, leading to the magnonic
manipulation of the spin superfluid. The theory for superfluid spin transport
within the domain wall is confirmed by numerical simulations.
PMID- 29341777
TI - High-Fidelity Single-Shot Singlet-Triplet Readout of Precision-Placed Donors in
Silicon.
AB - In this work we perform direct single-shot readout of the singlet-triplet states
in exchange coupled electrons confined to precision-placed donor atoms in
silicon. Our method takes advantage of the large energy splitting given by the
Pauli-spin blockaded (2,0) triplet states, from which we can achieve a single
shot readout fidelity of 98.4+/-0.2%. We measure the triplet-minus relaxation
time to be of the order 3 s at 2.5 T and observe its predicted decrease as a
function of magnetic field, reaching 0.5 s at 1 T.
PMID- 29341778
TI - Entanglement-Enhanced Radio-Frequency Field Detection and Waveform Sensing.
AB - We demonstrate a new technique for detecting the amplitude of arbitrarily chosen
components of radio-frequency waveforms based on stroboscopic backaction evading
measurements. We combine quantum nondemolition measurements and stroboscopic
probing to detect waveform components with magnetic sensitivity beyond the
standard quantum limit. Using an ensemble of 1.5*10^{6} cold rubidium atoms, we
demonstrate entanglement-enhanced sensing of sinusoidal and linearly chirped
waveforms, with 1.0(2) and 0.8(3) dB metrologically relevant noise reduction,
respectively. We achieve volume-adjusted sensitivity of deltaBsqrt[V]~3.96
fTsqrt[cm^{3}/Hz], comparable to the best rf magnetometers.
PMID- 29341779
TI - Mesoscopic Transport in Electrostatically Defined Spin-Full Channels in Quantum
Hall Ferromagnets.
AB - In this work, we use electrostatic control of quantum Hall ferromagnetic
transitions in CdMnTe quantum wells to study electron transport through
individual domain walls (DWs) induced at a specific location. These DWs are
formed due to the hybridization of two counterpropagating edge states with
opposite spin polarization. Conduction through DWs is found to be symmetric under
magnetic field direction reversal, consistent with the helical nature of these
DWs. We observe that long domain walls are in the insulating regime with a
localization length of 4-6 MUm. In shorter DWs, the resistance saturates to a
nonzero value at low temperatures. Mesoscopic resistance fluctuations in a
magnetic field are investigated. The theoretical model of transport through
impurity states within the gap induced by spin-orbit interactions agrees well
with the experimental data. Helical DWs have the required symmetry for the
formation of synthetic p-wave superconductors. The achieved electrostatic control
of a single helical domain wall is a milestone on the path to their
reconfigurable network and ultimately to a demonstration of the braiding of non
Abelian excitations.
PMID- 29341780
TI - Interplay of Correlations and Kohn Anomalies in Three Dimensions: Quantum
Criticality with a Twist.
AB - A general understanding of quantum phase transitions in strongly correlated
materials is still lacking. By exploiting a cutting-edge quantum many-body
approach, the dynamical vertex approximation, we make important progress,
determining the quantum critical properties of the antiferromagnetic transition
in the fundamental model for correlated electrons, the Hubbard model in three
dimensions. In particular, we demonstrate that-in contradiction to the
conventional Hertz-Millis-Moriya theory-its quantum critical behavior is driven
by the Kohn anomalies of the Fermi surface, even when electronic correlations
become strong.
PMID- 29341781
TI - Valley-Polarized Quantum Anomalous Hall Effect in Ferrimagnetic Honeycomb
Lattices.
AB - The valley-polarized quantum anomalous Hall effect (VP-QAHE), which combines
valleytronics and topology in one material, is of significant fundamental and
practical importance in condensed-matter physics and materials science. In
previous model studies, VP-QAHE occurs under strong Rashba spin-orbit coupling
(SOC), which is an extrinsic effect. Here, using a low energy k.p model, we
propose a different mechanism of VP-QAHE by introducing an intrinsic staggered
magnetic exchange field and develop a general picture of valley dependent band
inversion in honeycomb lattice. Using first-principles calculation, this new
mechanism is further demonstrated in the Co decorated In-triangle adlayer on a
Si(111) surface. This system is equivalent to a ferrimagnetic honeycomb lattice,
and the supported adlayer is experimentally more feasible in synthesis, thus
exhibiting advantages over the existing studies based on Rashba SOC and free
standing sheets. The underlying physical mechanism is generally applicable,
opening a new avenue for exploration of substrate supported VP-QAHE.
PMID- 29341782
TI - Complex Quasi-Two-Dimensional Crystalline Order Embedded in VO_{2} and Other
Crystals.
AB - Metal oxides such as VO_{2} undergo structural transitions to low-symmetry phases
characterized by intricate crystalline order, accompanied by rich electronic
behavior. We derive a minimal ionic Hamiltonian based on symmetry and local
energetics which describes structural transitions involving all four observed
phases, in the correct order. An exact analysis shows that complexity results
from the symmetry-induced constraints of the parent phase, which forces ionic
displacements to form multiple interpenetrating groups using low-dimensional
pathways and distant neighbors. Displacements within each group exhibit
independent, quasi-two-dimensional order, which is frustrated and fragile. This
selective ordering mechanism is not restricted to VO_{2}: it applies to other
oxides that show similar complex order.
PMID- 29341783
TI - Bell Inequalities Tailored to Maximally Entangled States.
AB - Bell inequalities have traditionally been used to demonstrate that quantum theory
is nonlocal, in the sense that there exist correlations generated from composite
quantum states that cannot be explained by means of local hidden variables. With
the advent of device-independent quantum information protocols, Bell inequalities
have gained an additional role as certificates of relevant quantum properties. In
this work, we consider the problem of designing Bell inequalities that are
tailored to detect maximally entangled states. We introduce a class of Bell
inequalities valid for an arbitrary number of measurements and results, derive
analytically their tight classical, nonsignaling, and quantum bounds and prove
that the latter is attained by maximally entangled states. Our inequalities can
therefore find an application in device-independent protocols requiring maximally
entangled states.
PMID- 29341784
TI - Fractional Transport in Strongly Turbulent Plasmas.
AB - We analyze statistically the energization of particles in a large scale
environment of strong turbulence that is fragmented into a large number of
distributed current filaments. The turbulent environment is generated through
strongly perturbed, 3D, resistive magnetohydrodynamics simulations, and it
emerges naturally from the nonlinear evolution, without a specific reconnection
geometry being set up. Based on test-particle simulations, we estimate the
transport coefficients in energy space for use in the classical Fokker-Planck
(FP) equation, and we show that the latter fails to reproduce the simulation
results. The reason is that transport in energy space is highly anomalous
(strange), the particles perform Levy flights, and the energy distributions show
extended power-law tails. Newly then, we motivate the use and derive the specific
form of a fractional transport equation (FTE), we determine its parameters and
the order of the fractional derivatives from the simulation data, and we show
that the FTE is able to reproduce the high energy part of the simulation data
very well. The procedure for determining the FTE parameters also makes clear that
it is the analysis of the simulation data that allows us to make the decision
whether a classical FP equation or a FTE is appropriate.
PMID- 29341785
TI - Total sleep deprivation does not significantly degrade semantic encoding.
AB - Sleep deprivation impairs performance on cognitive tasks, but it is unclear which
cognitive processes it degrades. We administered a semantic matching task with
variable stimulus onset asynchrony (SOA) and both speeded and self-paced trial
blocks. The task was administered at the baseline and 24 hours later after 30.8
hours of total sleep deprivation (TSD) or matching well-rested control. After
sleep deprivation, the 20% slowest response times (RTs) were significantly
increased. However, the semantic encoding time component of the RTs remained at
baseline level. Thus, the performance impairment induced by sleep deprivation on
this task occurred in cognitive processes downstream of semantic encoding.
PMID- 29341786
TI - Unscheduled adolescents return to the emergency department following acute
concussion.
AB - OBJECTIVE: Emergency department (ED) visits due to concussion have increased over
recent years. We aimed to identify variables associated with unscheduled
adolescents return to the ED. METHODS: A retrospective cohort study was
conducted. All children aged 11 to 18 years who were admitted to the ED due to
concussion between 2011 and 2016 were included. Multivariable logistic regression
was performed to identify predictors of ED return. RESULTS: Overall, 616
adolescents were admitted to the ED due to concussion. Within the first week from
discharge, 37/616 (6%) patients returned unscheduled to the ED, 21 (3.4%) during
the first 48 hours and 16 (2.6%) during the following 3-7 days. Age, gender,
ethnicity, diagnosis of concussion on first visit and length-of-stay in the ED
were not associated with unscheduled ED returns. Variables that were
independently associated with increased odds for an unscheduled ED return
included two or more symptoms of concussion [odds ratio (OR): 2.81; 95%
confidence interval (CI): (1.16-6.82)], bicycle or motor vehicle accident (OR:
3.48; 95% CI: 1.29-9.4), and performance of CT scan on first visit (OR: 2.47; 95%
CI: 1.12-5.48). CONCLUSIONS: The findings suggest that certain variables on the
first ED visit can predict an unscheduled return visit in adolescents.
ABBREVIATIONS: Emergency department (ED); Length of stay (LOS); computerised
tomography (CT).
PMID- 29341787
TI - The effects of early life polyunsaturated fatty acids and ruminant trans fatty
acids on allergic diseases: A systematic review and meta-analysis.
AB - Early life nutritional exposures could modify the gene expression and
susceptibility of allergic diseases (AD). This systematic review aimed to
evaluate whether early life (the first 1,000 days) natural exposure to
polyunsaturated fatty acids (PUFA) and ruminant trans fatty acids (R-TFA) could
affect the AD risk. We searched PubMed, EMBASE, PsycINFO, Scopus, the Cochrane
Library, and ClinicalTrials.gov from inception through September 10, 2017 for
relevant full-text articles in English. Observational studies were selected if
they examined the effects of early life PUFA or R-TFA on AD (eczema, asthma,
wheeze, and allergic rhinitis) or sensitization. The quality of studies was
examined by the Newcastle-Ottawa Scale, and the best evidence synthesis (BES) was
applied. We included 26 observational studies, and 8 of them showed high quality.
BES showed a moderate evidence for the protective effect of vaccenic acid (VA, an
R-TFA) on eczema, while insufficient or no evidence was found in other
associations. Meta-analysis showed that higher n-6/n-3 ratio and linoleic acid
were associated with higher risk of eczema (pooled odds ratio [OR] = 1.06, 95%
confidence intervals [CI]: 1.00 -1.13; 1.08, 95% CI: 1.01 -1.15). However, VA was
inversely associated with eczema pooled OR = 0.42, 95% CI: 0.25 -0.72). Early
life natural exposure to VA showed evident benefit on decreasing the risk of
eczema, while PUFA and other R-TFA showed limited effects on AD. More robust
studies especially for R-TFA are required.
PMID- 29341788
TI - Specific airway resistance is a better outcome parameter in bronchial provocation
testing compared to FEV1 in patients with bronchial asthma.
AB - OBJECTIVES: Asthma is a chronic inflammatory disease characterized by airway
hyperresponsiveness (AHR). A bronchial provocation test (BPT) is used to test for
AHR. However forced expiratory volume in one second (FEV1), used as outcome
parameter is effort-related, in contrast to specific airway resistance (sRaw).
This research was conducted to provide insight in the usefulness of sRaw as an
outcome parameter in BPT. METHODS: A total of 85 patients performing a BPT were
included in the study. Bronchial reactivity was defined as the provocative dosage
or provocative concentration causing a 20% decrease in FEV1 (PC-20) or a 100%
increase in sRaw (PC+100). RESULTS: No significant response in either FEV1 or
sRaw was found in 20 patients (24%). Twenty-nine patients (34%) only had a
positive response for sRaw; 24 out of these 29 patients recognized their
symptoms. 36 patients (42%) showed a positive response for both PC-20 and PC +
100. CONCLUSIONS: Twenty-nine patients (34%) showed a significant increase in
sRaw without a fall in FEV1. As performing sRaw is not a routine investigation,
these patients are at risk of being excluded from a diagnosis of asthma. We
suggest performing sRaw for patients without a fall in FEV1 during BPT when they
report recognizable symptoms.
PMID- 29341789
TI - Psychometric properties of the Epworth Sleepiness Scale: A factor analysis and
item-response theory approach.
AB - The purpose of this study is to examine the psychometric properties of the
Epworth Sleepiness Scale (ESS) in two languages, German and English. Students
from a university in Austria (N = 292; 55 males; mean age = 18.71 +/- 1.71 years;
237 females; mean age = 18.24 +/- 0.88 years) and a university in the US (N =
329; 128 males; mean age = 18.71 +/- 0.88 years; 201 females; mean age = 21.59 +/
2.27 years) completed the ESS. An exploratory-factor analysis was completed to
examine dimensionality of the ESS. Item response theory (IRT) analyses were used
to provide information about the response rates on the items on the ESS and
provide differential item functioning (DIF) analyses to examine whether the items
were interpreted differently between the two languages. The factor analyses
suggest that the ESS measures two distinct sleepiness constructs. These
constructs indicate that the ESS is probing sleepiness in settings requiring
active versus passive responding. The IRT analyses found that overall, the items
on the ESS perform well as a measure of sleepiness. However, Item 8 and to a
lesser extent Item 6 were being interpreted differently by respondents in
comparison to the other items. In addition, the DIF analyses showed that the
responses between German and English were very similar indicating that there are
only minor measurement differences between the two language versions of the ESS.
These findings suggest that the ESS provides a reliable measure of propensity to
sleepiness; however, it does convey a two-factor approach to sleepiness.
Researchers and clinicians can use the German and English versions of the ESS but
may wish to exclude Item 8 when calculating a total sleepiness score.
PMID- 29341791
TI - Population level evidence for seasonality of the human microbiome.
AB - The objective of this study is to determine whether human body odors undergo
seasonal modulation. We utilized google trends search volume from the United
States of America from January 1, 2010 to June 24, 2017 for a number of
predetermined body odors. Regression modeling of time series data was completed.
Our primary outcome was to determine the proportion of the variability in
Internet searches for each unpleasant odor (about the mean) that is explained by
a seasonal model. We determined that the seasonal (sinusoidal) model provided a
significantly better fit than the null model (best straight line fit) for all
searches relating to human body odors (P <.0001 for each). This effect was easily
visible to the naked eye in the raw time series data. Seasonality explained 88%
of the variability in search volume for flatulence (i.e. R2 = 0.88), 65% of the
variability in search volume for axillary odor, 60% of the variability in search
volume for foot odor, and 58% of the variability in search volume for bad breath.
Flatulence and bad breath tended to peak in January, foot odor in February, and
Axillary odor in July. We conclude that searching by the general public for
information on unpleasant body odors undergoes substantial seasonal variation,
with the timing of peaks and troughs varying with the body part involved. The
symptom burden of such smells may have a similar seasonal variation, as might the
composition of the commensal bacterial microflora that play a role in creating
them.
PMID- 29341792
TI - The blinding thyroid gland.
PMID- 29341790
TI - Postnatal tendon growth and remodeling require platelet-derived growth factor
receptor signaling.
AB - Platelet-derived growth factor receptor (PDGFR) signaling plays an important role
in the fundamental biological activities of many cells that compose
musculoskeletal tissues. However, little is known about the role of PDGFR
signaling during tendon growth and remodeling in adult animals. Using the
hindlimb synergist ablation model of tendon growth, our objectives were to
determine the role of PDGFR signaling in the adaptation of tendons subjected to a
mechanical growth stimulus, as well as to investigate the biological mechanisms
behind this response. We demonstrate that both PDGFRs, PDGFRalpha and PDGFRbeta,
are expressed in tendon fibroblasts and that the inhibition of PDGFR signaling
suppresses the normal growth of tendon tissue in response to mechanical growth
cues due to defects in fibroblast proliferation and migration. We also identify
membrane type-1 matrix metalloproteinase (MT1-MMP) as an essential proteinase for
the migration of tendon fibroblasts through their extracellular matrix.
Furthermore, we report that MT1-MMP translation is regulated by phosphoinositide
3-kinase/Akt signaling, while ERK1/2 controls posttranslational trafficking of
MT1-MMP to the plasma membrane of tendon fibroblasts. Taken together, these
findings demonstrate that PDGFR signaling is necessary for postnatal tendon
growth and remodeling and that MT1-MMP is a critical mediator of tendon
fibroblast migration and a potential target for the treatment of tendon injuries
and diseases.
PMID- 29341793
TI - Platelet transfusion does not improve outcomes in patients with brain injury on
antiplatelet therapy.
AB - INTRODUCTION: Platelet dysfunction following traumatic brain injury (TBI) is
associated with worse outcomes. The efficacy of platelet transfusion to reverse
antiplatelet medication (APM) remains unknown. Thrombelastography platelet
mapping (TEG-PM) assesses platelet function. We hypothesize that platelet
transfusion can reverse the effects of APM but does not improve outcomes
following TBI. METHODS: An observational study at six US trauma centres was
performed. Adult patients on APM with CT evident TBI after blunt injury were
enrolled. Demographics, brain CT and TEG-PM results before/after platelet
transfusion, length of stay (LOS), and injury severity score (ISS) were
abstracted. RESULTS: Sixty six patients were enrolled (89% aspirin, 50%
clopidogrel, 23% dual APM) with 23 patients undergoing platelet transfusion.
Transfused patients had significantly higher ISS and admission CT scores.
Platelet transfusion significantly reduced platelet inhibition due to aspirin
(76.0 +/- 30.2% to 52.7 +/- 31.5%, p < 0.01), but had a non-significant impact on
clopidogrel-associated inhibition (p = 0.07). Platelet transfusion was associated
with longer length of stay (7.8 vs. 3.5 days, p < 0.01), but there were no
differences in mortality. CONCLUSION: Platelet transfusion significantly
decreases platelet inhibition due to aspirin but is not associated with change in
outcomes in patients on APM following TBI.
PMID- 29341794
TI - Preseason Strength Assessment of the Rotator Muscles and Shoulder Injury in
Handball Players.
AB - CONTEXT: Few researchers have identified intrinsic risk factors for shoulder
injury in team handball players by analyzing measurements of maximal isokinetic
rotator muscle strength. OBJECTIVE: To identify possible intrinsic risk factors
for shoulder injury by analyzing measurements of maximal isokinetic rotator
muscle strength. DESIGN: Cross-sectional study. SETTING: Male team handball
senior divisions (the highest level) in France and Belgium. PATIENTS OR OTHER
PARTICIPANTS: A total of 108 male high-level handball players (age = 24 +/- 4
years, height = 189 +/- 6 cm, mass = 87 +/- 11 kg) were enrolled. MAIN OUTCOME
MEASURE(S): All players completed a preseason questionnaire and performed a
bilateral isokinetic assessment of the shoulder rotator muscles. On a monthly
questionnaire, players reported any shoulder injury that they sustained during
the season. RESULTS: On the preseason questionnaire, 51 of 108 (47%)
participants reported a history of dominant-shoulder injury. A total of 106
participants completed the in-season questionnaire, with 22% (n = 23) reporting a
shoulder injury on their dominant side during the subsequent season. Fourteen
percent (n = 15) sustained microtraumatic injuries, and 8% (n = 8) described a
traumatic injury. Backcourt players had a 3.5-times increased risk of injury
during the new season compared with players in other positions. Among the
isokinetic results, no risk factor for further injury was identified in handball
players with microtraumatic injuries. For traumatic injuries, the concentric
maximal strength developed by the internal rotators at high speed (240 degrees
/s) in the dominant shoulder was a protective factor against the risk of further
injury. CONCLUSIONS: These results can potentially identify intrinsic risk
factors for shoulder injury and may be used to determine potential interventions
for reducing this risk in handball players.
PMID- 29341762
TI - First Observation of a Baryonic B_{s}^{0} Decay.
AB - We report the first observation of a baryonic B_{s}^{0} decay, B_{s}^{0}
>pLambda[over -]K^{-}, using proton-proton collision data recorded by the LHCb
experiment at center-of-mass energies of 7 and 8 TeV, corresponding to an
integrated luminosity of 3.0 fb^{-1}. The branching fraction is measured to be
B(B_{s}^{0}->pLambda[over -]K^{-})+B(B_{s}^{0}->p[over -]LambdaK^{+})=[5.46+/
0.61+/-0.57+/-0.50(B)+/-0.32(f_{s}/f_{d})]*10^{-6}, where the first uncertainty
is statistical and the second systematic, the third uncertainty accounts for the
experimental uncertainty on the branching fraction of the B^{0}->pLambda[over
]pi^{-} decay used for normalization, and the fourth uncertainty relates to the
knowledge of the ratio of b-quark hadronization probabilities f_{s}/f_{d}.
PMID- 29341795
TI - The Ability to Provide Quality Chest Compressions Over Lacrosse Shoulder Pads.
AB - CONTEXT: Performance of quality cardiopulmonary resuscitation is essential for
improving patient outcomes. Performing compressions over football equipment
inhibits compression depth and rate, but lacrosse equipment has not yet been
studied. OBJECTIVE: To assess the effect of lacrosse shoulder pads on the
ability to provide quality chest compressions on simulation manikins. DESIGN:
Crossover study. SETTING: Simulation laboratory. PATIENTS OR OTHER
PARTICIPANTS: Thirty-six athletic trainers (12 men: age = 33.3 +/- 9.7 years;
24 women: age = 33.4 +/- 9.8 years). MAIN OUTCOME MEASURE(S): No shoulder pads
(NSP), Warrior Burn Hitman shoulder pads (WSP), and STX Cell II shoulder pads
(SSP) were investigated. Outcomes were chest-compression depth (millimeters),
rate (compressions per minute), rating of perceived exertion (0-10), hand
placement accuracy (%), and chest recoil (%). RESULTS: We observed a difference
in mean compression depth among shoulder-pad conditions ( F2,213 = 3.73, P = .03,
omega2 = 0.03), with a shallower depth during the WSP (54.1 +/- 5.8 mm) than the
NSP (56.8 +/- 5.7 mm; P = .02) trials. However, no differences were found in mean
compression rate ( F2,213 = 0.87, P = .42, omega2 = 0.001, 1-beta = .20). We
noted a difference in rating of perceived exertion scores ( F2,213 = 16.41, P <
.001, omega2 = 0.12). Compressions were more difficult during the SSP condition
(4.1 +/- 1.3) than during the NSP (2.9 +/- 1.2; P < .001) and WSP (3.3 +/- 1.1; P
= .002) conditions. A difference was present in hand-placement accuracy among the
3 shoulder-pad conditions (chi22 = 11.14, P = .004). Hand-placement accuracy was
better in the NSP than the SSP condition ( P = .002) and the SSP than the WSP
condition ( P = .001). CONCLUSIONS: Lacrosse shoulder pads did not inhibit the
ability to administer chest compressions with adequate rate and depth. With
appropriate training to improve hand placement, the pads may be left in place
while cardiopulmonary resuscitation is initiated during sudden cardiac arrest.
PMID- 29341796
TI - Correction to: Missed medical appointments during shifts to and from daylight
saving time.
PMID- 29341799
TI - DIGEST.
PMID- 29341798
TI - Phenolic Constituents and Inhibitory Effects of Hibiscus sabdariffa L. (Sorrel)
Calyx on Cholinergic, Monoaminergic, and Purinergic Enzyme Activities.
AB - This study revealed the effect of phenolic extract from Hibiscus sabdariffa L.
(sorrel) calyx on acetylcholinesterase (AChE), butyrylcholinesterase (BChE),
monoamine oxidase (MAO), and ecto-5' nucleotidase (E-NTDase) activities as well
as pro-oxidant-induced oxidative damage in rat brain in vitro. Sorrel extract
inhibited AChE (EC50 = 46.96 ug/mL), BChE (EC50 = 40.38 ug/mL), MAO (EC50 = 43.69
ug/mL), and E-NTDase (EC50 = 40.52 ug/mL) and stimulated Na+/K+-ATPase (EC50 =
22.01 ug/mL) activities. The phenolic extract also reduced Fe2+- (EC50 = 22.37
ug/mL) and sodium nitroprusside- (SNP-) (21.46 ug/mL) induced malondialdehyde
(MDA) production in rat brain homogenates. Catechin (53.12 mg/g), chlorogenic
(67.12 mg/g), rutin (16.25 mg/g), and caffeic acid (15.38 mg/g) were the most
abundant phenolic compounds in the extract. The synergistic effects of the
phenolic compounds may contribute to the enzyme inhibitory and stimulatory
activities of the extract. Our findings suggest that sorrel extract shows
promising potential for the treatment and/or management of some neurodegenerative
diseases such as Alzheimer's disease and Parkinson's disease.
PMID- 29341800
TI - Factors Associated with Patient Satisfaction in an Outpatient Glaucoma
Population.
AB - PURPOSE: To determine what metrics might impact satisfaction survey responses.
METHODS: A 37-question survey was administered to 249 participants. Responses
were correlated to demographics, clinical factors, weather conditions, and
examination timing. RESULTS: Sample consists of 55.4% female and 73.9% white, and
mean age was 65.1 years. Participants were assigned to: completely satisfied
(77.9%) or not completely satisfied (22.1%) groups based on their rating of
glaucoma specialist on a scale of 1-10, while 10 considered "completely
satisfied" and less than 10 "not completely satisfied." Complete satisfaction was
associated with ability to schedule appointments early, phone calls
answered/returned same day, shorter perceived wait time, and better communication
skills of ophthalmologist (p < 0.05). Completely satisfied participants reported
their ophthalmologist spent enough time with them, listened carefully, and
communicated in an understandable way (p < 0.05). CONCLUSIONS: The majority of
factors found to be associated with patient satisfaction were related to
characteristics of the ophthalmologists and their office.
PMID- 29341797
TI - Visual dependence affects postural sway responses to continuous visual field
motion in individuals with cerebral palsy.
AB - : The current study aimed to explore the impact of visual dependence on
sensorimotor coupling of postural sway and visual motion in adults and teens with
spastic cerebral palsy (CP). We hypothesized that individuals with CP would
exhibit greater magnitudes of sway than healthy individuals, and the presence of
visual dependence (VD) would produce instability in the direction of visual
motion. Participants stood in a virtual environment in which the visual scene
remained static or continuously rotated 30 degree/second in pitch-up or pitch
down. Increased center of pressure and center of mass responses were observed in
the direction of visual scene motion in those with CP. Those with VD exhibited
reduced frequency responses in anterior-posterior direction than those who were
visually independent. VD suggests deficient sensorimotor integration that could
contribute to postural instability and reduced motor function. Individuals with
CP who are visually dependent may benefit from more sensory focused
rehabilitation strategies. ABBREVIATIONS: AP, anterior-posterior; CP, cerebral
palsy; COM, center of mass; COP, center of pressure; MDF, median frequency; ML,
mediolateral; PD, pitch down (nose down) rotation; PU, pitch up (nose up)
rotation; RFT, rod and frame test; RMS, root mean square; SLP, slope of the
fitted line; TD, typical development; VD, visual dependence; VI, visual
independence; VOR, vestibulo-ocular reflex; VPI, visual perceptual impairment.
PMID- 29341801
TI - Local vs. national: Epidemiology of pedestrian injury in a mid-Atlantic city.
AB - OBJECTIVE: Understanding pedestrian injury trends at the local level is essential
for program planning and allocation of funds for urban planning and improvement.
Because we hypothesize that local injury trends differ from national trends in
significant and meaningful ways, we investigated citywide pedestrian injury
trends to assess injury risk among nationally identified risk groups, as well as
identify risk groups and locations specific to Baltimore City. METHODS:
Pedestrian injury data, obtained from the Baltimore City Fire Department, were
gathered through emergency medical services (EMS) records collected from January
1 to December 31, 2014. Locations of pedestrian injuries were geocoded and
mapped. Pearson's chi-square test of independence was used to investigate
differences in injury severity level across risk groups. Pedestrian injury rates
by age group, gender, and race were compared to national rates. RESULTS: A total
of 699 pedestrians were involved in motor vehicle crashes in 2014-an average of 2
EMS transports each day. The distribution of injuries throughout the city did not
coincide with population or income distributions, indicating that there was not a
consistent correlation between areas of concentrated population or concentrated
poverty and areas of concentrated pedestrian injury. Twenty percent (n = 138) of
all injuries occurred among children age <=14, and 22% (n = 73) of severe
injuries occurred among young children. The rate of injury in this age group was
5 times the national rate (Incident Rate Ratio [IRR] = 4.81, 95% confidence
interval [CI], [4.05, 5.71]). Injury rates for adults >=65 were less than the
national average. CONCLUSIONS: As the urban landscape and associated pedestrian
behavior transform, continued investigation of local pedestrian injury trends and
evolving public health prevention strategies is necessary to ensure pedestrian
safety.
PMID- 29341802
TI - Portulaca oleracea L. Extract Enhances Glucose Uptake by Stimulating GLUT4
Translocation to the Plasma Membrane in 3T3-L1 Adipocytes.
AB - This study investigated the effects of Portulaca oleracea L. extract on glucose
uptake in 3T3-L1 adipocytes. P. oleracea extract (POE) markedly enhanced glucose
uptake, which was caused by increased GLUT4 expression at the plasma membrane
(PM) in 3T3-L1 adipocytes. This increase in PM-GLUT4 expression was associated
with insulin receptor substrate-1 (IRS-1) phosphorylation, phosphatidylinositol 3
kinase (PI3K) activation, and Akt phosphorylation, and finally, enhanced
intracellular glucose uptake. POE was not associated with protein kinase C
(PKC)lambda/zeta phosphorylation in the insulin signaling pathway, but did
promote 5'-AMP-activated kinase (AMPK) phosphorylation. Increased glucose uptake
through POE was inhibited through treating with the PI3K inhibitor or AMPK
inhibitor in 3T3-L1 adipocytes. This result suggested that POE may enhance
glucose uptake by stimulating GLUT4 translocation to the PM through activating
the PI3K and AMPK pathway in 3T3-L1 adipocytes.
PMID- 29341804
TI - Benefits and logistics of nonpresenting undergraduate students attending a
professional scientific meeting.
PMID- 29341803
TI - Licorice Pretreatment Protects Against Brain Damage Induced by Middle Cerebral
Artery Occlusion in Mice.
AB - Licorice is extracted from the roots of plants in the Glycyrrhiza genus,
especially Glycyrrhiza uralensis in China and Korea. It has several
pharmacological activities, including neuro-protective, anti-fungal, and anti
cariogenic effects. Ischemia/reperfusion-induced brain injury is a leading cause
of adult disability and death; thus, the identification of anti-apoptotic, neuro
protective therapeutic agents is viewed as an attractive drug development
strategy. Infarct volumes and the expression of several apoptosis-related
proteins, including Bcl-xL, Bcl-2, caspase-8, and caspase-9, were evaluated by
western blotting in the brains of mice subjected to middle cerebral artery
occlusion (MCAO). Three consecutive days of oral pretreatment with the methanol
extract of licorice (GRex) significantly reduced infarct volumes 24 h after MCAO.
In addition, GRex effectively inhibited the activation of caspase-9 by
upregulating protein expression of Bcl-xL and Bcl-2. The neuro-protective effect
of licorice was due to its regulation of apoptosis-related proteins. These data
suggest that licorice could be a potential candidate for the treatment of
ischemia-induced brain damage.
PMID- 29341805
TI - A case study approach, combined with modified team-based learning, to teach the
progression of metabolic syndrome to type 2 diabetes.
PMID- 29341806
TI - The membrane potential puzzle: a new educational game to use in physiology
teaching.
PMID- 29341807
TI - Active memory reactivation previous to the introduction of a new related content
improves students' learning.
PMID- 29341808
TI - Development of an open-access, web-based interactive tool to learn autonomic
nervous system physiology and pharmacology.
PMID- 29341809
TI - Modified directed self-learning sessions in physiology with prereading
assignments and Pecha Kucha talks: perceptions of students.
AB - The present study reports perceptions of first-year undergraduate medical
students ( n = 120), regarding modified directed self-learning (DSL) sessions in
physiology. Students were provided with prereading assignments (faculty developed
PowerPoint slides containing diagrams with incomplete labeling/flowcharts with
missing steps) pertaining to the DSL topic 1 wk before the scheduled small-group
DSL presentations. During DSL presentation sessions, which were facilitated by
teachers, a few students individually presented learning objectives in the
specified topic. Apart from that, students discussed answers for the questions in
the prereading assignment. Students were also given an opportunity to use
technology to support DSL, by way of involving them in Pecha Kucha (PK) talks.
The impact of the modified DSL method was determined by requesting students to
respond to a validated questionnaire. Frequency analysis of the responses
revealed that >60% of students were positive about the modified DSL sessions
improving their DSL, presentation, collaborative learning, and information
retrieving skills. Students agreed that PK talks helped them to learn how to
organize content (65%), present concise information (65.8%), and apply creativity
(72.5%). Even though small in number, there were comments that the prereading
assignments were useful for learning. The present study revealed that, even
though students actively participated in modified DSL sessions, their perceptions
on satisfaction and usefulness of the same toward achievement of various skills
were not encouraging. The study generated significant results, which implies that
undergraduate medical students should be oriented on the relevance of active
learning strategies in their future studies.
PMID- 29341810
TI - Beyond "formative": assessments to enrich student learning.
AB - Formative assessments can enhance and enrich student learning. Typically, these
have been used to provide feedback against end-of-course standards and prepare
students for summative assessments of performance or measurement of competence.
Here, we present the case for using assessments for learning to encompass a wider
range of important outcomes. We discuss 1) the rationale for using assessment for
learning; 2) guiding theories of expertise that inform assessment for learning;
3) theoretical and empirical evidence; 4) approaches to rigor and validation; and
5) approaches to implementation at multiple levels of the curriculum. The
literature strongly supports the use of assessments as an opportunity to
reinforce and enhance learning. Physiology teachers have a wide range of
theories, models, and interventions from which to prepare students for retention,
application, transfer, and future learning by using assessments.
PMID- 29341811
TI - Impact of distance education via interactive videoconferencing on students'
course performance and satisfaction.
AB - The impact of distance education via interactive videoconferencing on pharmacy
students' performance in a course was assessed after implementation of a distance
campus. Students filled out a "Student Demographic Survey" and a "Precourse
Knowledge Assessment" at the start of the course and a "Postcourse Knowledge
Assessment" and a "Postcourse Student Perceptions Survey" at the end of the
course. The primary end point, a comparison of course grades (%) between the main
and distance campuses, was examined using the two-sample t-test. We examined the
relationships among demographics, campus location, course grades, grade point
average, pre- and postcourse knowledge assessments, and postcourse perceptions as
our secondary end points with parametric and nonparametric tests. Data from 93
students were included in the analysis [main campus ( n = 81); distance campus (
n = 12)]. Students on the main campus achieved a significantly higher final
course grade (87 vs. 81%; P = 0.02). Scores on the Postcourse Knowledge
Assessment were also significantly higher compared with those of students on the
distance education campus (77 vs. 68%; P = 0.04). Students on both campuses
reported self-perceived improvement in their knowledge base regarding various
aspects of infectious diseases. Compared with the students on the distance
campus, those on the main campus were more likely to subjectively perceive that
they had succeeded in the course ( P = 0.04). Our study suggests that students on
the main campus achieved a higher final course grade and were more likely to feel
that they had succeeded in the course. Students on both campuses reported
improvement in knowledge.
PMID- 29341812
TI - Optional anatomy and physiology e-learning resources: student access, learning
approaches, and academic outcomes.
AB - Anatomy and physiology interactive video clips were introduced into a blended
learning environment, as an optional resource, and were accessed by ~50% of the
cohort. Student feedback indicated that clips were engaging, assisted
understanding of course content, and provided lecture support. Students could
also access two other optional online resources, lecture capture recordings and
an interactive atlas of anatomy, and individuals were tracked with respect to
their access behavior, learning approach, and subject score. Deep learning was
highest among those accessing the clips or atlas or those accessing more online
resources, and thus self-regulatory skill development might be a useful approach
to increase student access to optional online resources. Those who accessed
clips, lecture capture recordings, or atlas achieved a significantly higher
subject score than those who did not. When combinations of resources used were
considered, we found an approximately linear relationship between number of
resources accessed and subject score, with a 16% difference in score between
those who accessed none or all of the resources. However, the low resource access
rate suggests that academic advantage may not be simply due to the learning
support offered by the resources. As students accessing the optional resources
tended to be more self-regulated, it may be that it was the extra effort made
with respect to other subject resources, rather than just the access to the
online resources, that contributed to higher subject score. Further studies are
required to establish the relationships between academic performance, optional
online resource access, and deep learning.
PMID- 29341813
TI - Regenerative medicine: a vehicle to infuse laboratory-bench modules into an
exercise physiology curriculum.
AB - Regenerative medicine is a novel discipline that both excites undergraduates and
may be used as a vehicle to expose students to scientific concepts and
opportunities. The goal of this article is to describe the implementation of a
National Science Foundation-funded Targeted Infusion Project in which
underrepresented minority undergraduates are exposed to laboratory-bench skills
and summer research opportunities that they may not have encountered otherwise. A
3-wk infusion of laboratory-bench and data presentation skills, in the context of
a regenerative medicine/bioengineering project, aimed to engage students and
expose them to opportunities as summer researchers and teaching assistants. The
infusion aimed to assess the extent to which students improved 1) attitudes
toward laboratory-bench-based techniques, using attitudes toward science as a
proxy; 2) perceptions of scientific inquiry; 3) intentions to engage in
undergraduate research; and 4) intentions to persist in science, technology,
engineering, and mathematics (STEM)-related fields. Results indicate that the 3
wk infusion had no effect on science attitudes, but transcribed responses to
structured interviews administered after the summer research experience indicated
that students who completed summer research projects had positive experiences.
Differences in intentions to engage in research were detected between groups of
students in different STEM majors, in addition to differences in intentions to
pursue a career in science. We describe the implementation of the infusion and
briefly discuss quantitative outcomes. We conclude that infusion of laboratory
bench modules in the context of a regenerative medicine/bioengineering project
may play a small but important role in increasing (minority) participation and
persistence in the STEM pipeline.
PMID- 29341814
TI - Utilizing a rat delayed implantation model to teach integrative endocrinology and
reproductive biology.
AB - In this teaching laboratory, the students are directed in an exercise that
involves designing and performing an experiment to determine estrogen's role in
regulating delayed implantation (diapause) in female rats. To encourage active
participation by the students, a discussion question is provided before the
laboratory exercise in which each student is asked to search the literature and
provide written answers to questions and to formulate an experiment to test the
role of ovarian estrogen in inducing implantation in female rats. One week before
the laboratory exercise, students discuss their answers to the questions with the
instructor to develop an experiment to test their hypothesis that estrogen is
involved with inducing implantation in the rat. A rat delayed implantation model
was established that utilizes an estrogen receptor antagonist (ICI 182,780),
which inhibits the action of ovarian estrogens. Groups of mated females are
treated with either carrier (control) or ICI 182,780 (ICI) every other day,
starting on day 2 postcoitus (pc) until day 8 pc. One-half of the females
receiving ICI are injected with estradiol-17beta on day 8 pc to induce
implantation 4 days after the controls. If the ICI-treated females are not
administered estradiol, embryo implantation occurs spontaneously ~4 days after
the last ICI injection on day 8. This is a very simple protocol that is very
effective and provides an excellent experiment for student discussion on hormone
action and the use of agonists and antagonists.
PMID- 29341815
TI - Development and validation of simulated virtual patients to impart early clinical
exposure in endocrine physiology.
AB - In the country presently, preclinical medical students are not routinely exposed
to real patients. Thus, when they start clinical postings, they are found to have
poor clinical reasoning skills. Simulated virtual patients (SVPs) can improve
clinical skills without endangering real patients. This pilot study describes the
development of two SVPs in endocrine physiology and their validation in terms of
acquisition of clinical knowledge and student engagement. Two SVPs, Nandini
Sharma (unintentional weight gain) and Sunil Yadav (polyuria), were created and
published on the i-Human Patients platform through an iterative,
interdisciplinary, and transdisciplinary collaborative process using the
conceptual framework of Kim et al. (Kim S, Phillips WR, Pinsky L, Brock D,
Phillips K, Keary J. Med Educ 40: 867-876, 2006). After internal and external
peer validation, the SVPs were piloted on 40 students (20 students per virtual
patient) over 2 wk. A cognitive pretest was conducted before exposure, and a
posttest soon after. Faculty and student feedback were collected. Faculty found
SVPs authentic, helpful as teaching-learning tools, and useful for giving
feedback and for assessment. Students found SVPs more engaging than paper cases
and helpful in developing clinical reasoning and in imparting clinical exposure.
Pretest and posttest scores indicated knowledge gain ( P < 0.01). Although
challenging to create, SVPs created on the i-Human Patients platform improved
learning in endocrine physiology and were well accepted by students and faculty
as a means to provide early clinical exposure. More SVPs can be developed through
collaboration between stakeholder departments and integrated into the curriculum
for greater benefit.
PMID- 29341816
TI - Red cell indexes made easy using an interactive animation: do students and their
scores concur?
AB - A good understanding of red cell indexes can aid medical students in a
considerable manner, serving as a basis to unravel both concepts in red cell
physiology and abnormalities associated with the same. In this study, we tried to
assess whether an interactive animation was helpful in improving student
comprehension and understanding of red cell indexes compared with conventional
classroom teaching. Eighty-eight first-year MBBS students participated, of which
44 were assigned to group A and 44 were assigned to group B after randomization.
After further creation of smaller groups, students were provided with 45 min to
revise red cell indexes, after which they were required to complete a multimodal
questionnaire. Group A subgroups used written material for revision, whereas
group B subgroups had access to an interactive animation. After completion of the
questionnaire, group A students also used the animation after which feedback was
collected from all students. Efficacy of the animation to improve learning and
retention was demonstrated, as group B students scored significantly higher than
group A students on the questionnaire ( P = 0.0003). A clear majority of the
students agreed/strongly agreed that the animation was easy to operate, conveyed
important concepts efficiently, and improved their knowledge of related clinical
aspects as well. From the results and feedback, we found that the animation was a
simple, well-received model, which, by significantly improving student
performance, corroborated our hypothesis that inclusion of interactive animation
into student curriculum can advance their academic attainment, compared with
didactic teaching alone.
PMID- 29341817
TI - Setting national guidelines for physiology undergraduate degree programs.
PMID- 29341818
TI - Medicine as It Should Be: Teaching Team and Teamwork during a Palliative Care
Clerkship.
AB - BACKGROUND: Interprofessional Education (IPE) is an important component of
medical education. Rotations with palliative care interdisciplinary teams (IDTs)
provide an optimal environment for IPE and teaching teamwork skills. OBJECTIVE:
Our objective was to assess the learning of senior medical students during a
palliative care rotation. DESIGN: A constant comparison method based on grounded
theory was used in this qualitative study. SETTING/SUBJECTS: Senior medical
students completed a semi-structured reflective writing exercise after a required
one-week palliative care clerkship. Sixty randomly selected reflective writings
were analyzed. MEASUREMENTS: The reflective writings were analyzed to evaluate
the student's experiences. RESULTS: Dominant themes identified were related to
teams and teamwork. Eight specific themes were identified: value of IDT for team
members; value of IDT for patient/family; importance of each team member;
reliance on other team members; roles of team members; how teams work; team
communication; and interdisciplinary assessment and care planning. Students
described exposure to novel experiences and planned to incorporate newly learned
behaviors in their future practice. CONCLUSION: By participating in palliative
care IDTs, medical students consistently learned about teamwork within
healthcare. Additionally, they learned the importance of such teamwork to
patients and the team itself. Rotations with palliative care IDTs have a
significant role to play in IPE and preparing medical students to practice on
teams.
PMID- 29341819
TI - From the desk of Peter F. Buckley, MD.
PMID- 29341820
TI - Comments on Abilify MyCite.
PMID- 29341821
TI - Deuterium Tetrabenazine for Tardive Dyskinesia.
AB - Tardive dyskinesia remains a significant, potentially stigmatizing or crippling
adverse effect for any patient treated with an antipsychotic medication. While
second- and third-generation antipsychotics have exhibited lower annual incidence
rates for tardive dyskinesia than classic or first-generation agents, 3.9% versus
5.5%, the estimated incidence rate is only modestly lower. When coupled with the
fact that second- and third-generation antipsychotic medications have come to be
employed in treating a wider range of disorders (e.g., autism spectrum disorders,
mood disorders, personality disorders, etc.), it is clear that the population of
patients exposed to the risk of tardive dyskinesia has expanded. On April 3,
2017, the U.S. Food and Drug Administration (FDA) approved a deuterated version
of tetrabenazine (Xenozine(r)) for the treatment of the involuntary choreic
movements associated with Huntington's disease. More recent data, however, have
indicated that deuterium tetrabenazine or deutetrabenazine (Austedo(r)) is
effective in treating tardive dyskinesia. Moreover, like the other derivative of
tetrabenazine, valbenazine (Ingrezza(r)), deutetrabenazine offers less frequent
dosing and a better short-term adverse effect profile than that of tetrabenazine.
Longer use in a broader range of patients, however, will be required to identify
risks and benefits not found in short-term trials, as well as optimal use
parameters for treatment of tardive dyskinesia.
PMID- 29341822
TI - Aripiprazole Long-Acting Injectable for Maintenance Treatment of Bipolar I
Disorder in Adults.
AB - Bipolar I disorder is a serious and disabling psychiatric illness. It is
associated with a significant reduction in quality of life and an increased risk
for suicide. Pharmacotherapy is essential for both the acute and maintenance
treatment of bi-polar I disorder. While multiple oral medications are recommended
for the maintenance treatment, there are not many long-acting injectable
medications approved for this indication. New treatments that would improve
patient adherence have the potential for decreasing relapses and improving
patients' ability to remain functional members of society. In this paper we
discuss the available data for safety and efficacy of aripiprazole long-acting
injectable in bipolar disorder.
PMID- 29341823
TI - Clinical News.
PMID- 29341824
TI - Intestinal lymph as a readout of meal-induced GLP-1 release in an unrestrained
rat model.
AB - Intestinal lymph supposedly provides a readout for the secretion of intestinal
peptides. We here assessed how mesenteric lymph duct (MLD) lymph levels of
glucagon-like peptide (GLP-1), insulin, and metabolites [glucose and
triglycerides (TG)] evolve after isocaloric high- and low-fat diet (HFD and LFD)
meals and how they compare with hepatic portal vein (HPV) plasma levels.
Moreover, we examined the effects of intraperitoneally administered GLP-1 (1 or
10 nmol/kg) on these parameters. At 20 min after the HFD meal onset, GLP-1 levels
were higher in MLD lymph than in HPV plasma. No such difference occurred with the
LFD meal. Intraperitoneal injections of 10 nmol/kg GLP-1 before meals enhanced
the meal-induced increases in MLD lymph and HPV plasma GLP-1 levels except for
the MLD lymph levels after the HFD meal. Intraperitoneal injection of 1 nmol/kg
GLP-1 only increased HPV plasma GLP-1 levels at 60 min after the HFD meal. GLP-1
injections did not increase the MLD lymph or HPV plasma GLP-1 concentrations
beyond the physiological range, suggesting that intraperitoneal GLP-1 injections
can recapitulate the short-term effects of endogenous GLP-1. Dipeptidyl peptidase
IV (DPP-IV) activity in MLD lymph was lower than in HPV plasma, which presumably
contributed to the higher levels of GLP-1 in lymph than in plasma. Insulin and
glucose showed similar profiles in MLD lymph and HPV plasma, whereas TG levels
were higher in lymph than in plasma. These results indicate that intestinal lymph
provides a sensitive readout of intestinal peptide release and potential action,
in particular when fat-rich diets are consumed.
PMID- 29341825
TI - A predictive model of rat calorie intake as a function of diet energy density.
AB - Easy access to high-energy food has been linked to high rates of obesity in the
world. Understanding the way that access to palatable (high fat or high calorie)
food can lead to overconsumption is essential for both preventing and treating
obesity. Although the body of studies focused on the effects of high-energy diets
is growing, our understanding of how different factors contribute to food choices
is not complete. In this study, we present a mathematical model that can predict
rat calorie intake to a high-energy diet based on their ingestive behavior to a
standard chow diet. Specifically, we propose an equation that describes the
relation between the body weight ( W), energy density ( E), time elapsed from the
start of diet ( T), and daily calorie intake ( C). We tested our model on two
independent data sets. Our results show that the suggested model can predict the
calorie intake patterns with high accuracy. Additionally, the only free parameter
of our proposed equation (rho), which is unique to each animal, has a strong
correlation with their calorie intake.
PMID- 29341827
TI - Multitasking: a challenge for the kidney.
PMID- 29341826
TI - u-Opioid receptors inhibit the exercise pressor reflex by closing N-type calcium
channels but not by opening GIRK channels in rats.
AB - u-Opioid G protein-coupled receptors (MOR) interact with ion channels to decrease
neuronal excitability. In humans, intrathecal administration of the MOR agonist
fentanyl inhibits the exercise pressor reflex, an effect that can be attributed
to either the opening of inward rectifying potassium channels (GIRK) or the
closing of N-type calcium channels. The purpose of this study was to determine if
the highly selective MOR agonist [d-Ala2, N-MePhe4,Gly-ol]-enkephalin (DAMGO)
attenuates the exercise pressor reflex and which of these two channels are
responsible for this effect. In decerebrate rats, we determined the effect of
intrathecal injection of either tertiapin-LQ, which blocks the GIRK channel or
omega-conotoxin-GVIA, which blocks the N-type calcium channel on the exercise
pressor reflex, which was evoked by contracting the triceps surae muscles.
Initially, we established that intrathecal injection of DAMGO inhibited the
exercise pressor reflex relative to no intrathecal injection or intrathecal
saline injection ( P < 0.001, n = 5). We then found that intrathecal injection of
two doses of tertiapin-LQ (1 and 10 ug) had no effect on the exercise pressor
reflex ( n = 6 and n = 7, respectively; P > 0.05). Importantly, neither dose of
tertiapin-LQ prevented the DAMGO-induced inhibition of the exercise pressor
reflex. Last, we found that intrathecal injection of omega-conotoxin-GVIA
markedly attenuated the exercise pressor reflex ( P < 0.001, n = 7). The
cardioaccelerator response to contraction did not appear to be effected in any of
the experiments. We conclude that N-type voltage-gated calcium channel inhibition
appears to be the mechanism by which MOR activation inhibits the exercise pressor
reflex in decerebrate rats.
PMID- 29341828
TI - Biosensors for spatiotemporal detection of reactive oxygen species in cells and
tissues.
AB - Redox biology has become a major issue in numerous areas of physiology. Reactive
oxygen species (ROS) have a broad range of roles from signal transduction to
growth control and cell death. To understand the nature of these roles, accurate
measurement of the reactive compounds is required. An increasing number of tools
for ROS detection is available; however, the specificity and sensitivity of these
tools are often insufficient. Furthermore, their specificity has been rarely
evaluated in complex physiological conditions. Many ROS probes are sensitive to
environmental conditions in particular pH, which may interfere with ROS detection
and cause misleading results. Accurate detection of ROS in physiology and
pathophysiology faces additional challenges concerning the precise localization
of the ROS and the timing of their production and disappearance. Certain ROS are
membrane permeable, and certain ROS probes move across cells and organelles.
Targetable ROS probes such as fluorescent protein-based biosensors are required
for accurate localization. Here we analyze these challenges in more detail,
provide indications on the strength and weakness of current tools for ROS
detection, and point out developments that will provide improved ROS detection
methods in the future. There is no universal method that fits all situations in
physiology and cell biology. A detailed knowledge of the ROS probes is required
to choose the appropriate method for a given biological problem. The knowledge of
the shortcomings of these probes should also guide the development of new
sensors.
PMID- 29341829
TI - Climatic modulation of neurotransmitter release in amphibian neuromuscular
junctions: role of dynorphin-A.
AB - Amphibian neuromuscular junctions (NMJs) become relatively more silent during the
dry winter season in Australia. During the dry, calcium sensitivity is reduced,
whereas calcium dependence remains unchanged. Endogenous opioid peptides play an
important role in the regulation of the physiological functions of active and
dormant vertebrates. Previous findings suggest that dynorphin-A is more potent
than other opiates in decreasing evoked neurotransmission in amphibian NMJs.
Dynorphin-A has been shown not to alter the amplitude or the frequency of
miniature quantal neurotransmitter release. In the present study, we report that
dynorphin-A exerted a more pronounced inhibitory effect on evoked
neurotransmitter release during the dry (hibernating period) when compared with
the wet (active period) season. Dynorphin-A increased the frequency and decreased
the amplitude of miniature neurotransmitter release only at relatively high
concentration during the dry season. In the present study, we propose that
dynorphin-A suppresses evoked neurotransmitter release and thus contraction of
skeletal muscles, while allowing subthreshold activation of the NMJ by miniature
neurotransmission, thus preventing any significant neuromuscular remodeling. The
inhibitory effect of dynorphin-A on evoked transmitter release is reduced by
increasing the extracellular calcium concentration.
PMID- 29341830
TI - Pregnancy-related hormones, progesterone and human chorionic gonadotrophin,
upregulate expression of maternal plasma gelsolin.
AB - Plasma gelsolin (pGSN), a protein primarily involved in clearance of circulating
actin filaments, is an upcoming novel biomarker. Its level changes in multiple
disease and injury conditions, attributable mainly to its consumption during
actin clearance; the endogenous regulation of its expression, however, remains
elusive as well as unexplored. Here, we are reporting the first isolation of the
promoter region of pGSN gene and investigation of its transcriptional regulation
during pregnancy (a natural process associated with a well-programmed injury
course of parturition). Interestingly, two of the pregnancy-related hormones,
human chorionic gonadotrophin (hCG) and progesterone, significantly upregulated
pGSN promoter activity in muscle cells. This action of both hormones was found to
mediate through their respective cellular receptors and involved a contribution
of multiple signaling pathways including those of protein kinase A, protein
kinase C, epidermal growth factor receptor and prostaglandin-endoperoxidase
synthase 2 in the case of hCG-mediated upregulation. This novel upregulation was
further supported by elevated levels of endogenous pGSN transcripts as well as
secreted protein upon hormonal treatments of muscle cells compared with untreated
controls. A participation of pGSN promoter cis-elements, capable of interacting
with endogenous transcription factors, Ap1, Sp1, and p300, was also observed
during this hormonal upregulation. Additionally, the augmented pGSN levels
observed in pregnant mice compared with the control animals further supported an
upregulation of this protein during pregnancy, implicating vital role(s) played
by pGSN during this period in mammals.
PMID- 29341831
TI - Role of Bone-Modifying Agents in Multiple Myeloma: American Society of Clinical
Oncology Clinical Practice Guideline Update.
AB - Purpose To update guideline recommendations on the role of bone-modifying agents
in multiple myeloma. Methods An update panel conducted a targeted systematic
literature review by searching PubMed and the Cochrane Library for randomized
controlled trials, systematic reviews, meta-analyses, clinical practice
guidelines, and observational studies. Results Thirty-five relevant studies were
identified, and updated evidence supports the current recommendations.
Recommendations For patients with active symptomatic multiple myeloma that
requires systemic therapy with or without evidence of lytic destruction of bone
or compression fracture of the spine from osteopenia on plain radiograph(s) or
other imaging studies, intravenous administration of pamidronate 90 mg over at
least 2 hours or zoledronic acid 4 mg over at least 15 minutes every 3 to 4 weeks
is recommended. Denosumab has shown to be noninferior to zoledronic acid for the
prevention of skeletal-related events and provides an alternative. Fewer adverse
events related to renal toxicity have been noted with denosumab compared with
zoledronic acid and may be preferred in this setting. The update panel recommends
that clinicians consider reducing the initial pamidronate dose in patients with
preexisting renal impairment. Zoledronic acid has not been studied in patients
with severe renal impairment and is not recommended in this setting. The update
panel suggests that bone-modifying treatment continue for up to 2 years. Less
frequent dosing has been evaluated and should be considered in patients with
responsive or stable disease. Continuous use is at the discretion of the treating
physician and the risk of ongoing skeletal morbidity. Retreatment should be
initiated at the time of disease relapse. The update panel discusses measures
regarding osteonecrosis of the jaw. Additional information is available at
www.asco.org/hematologic-malignancies-guidelines and www.asco.org/guidelineswiki
.
PMID- 29341832
TI - Racial Differences in 21-Gene Recurrence Scores Among Patients With Hormone
Receptor-Positive, Node-Negative Breast Cancer.
AB - Purpose The 21-gene recurrence score (RS) breast cancer assay is clinically used
to quantify risk of 10-year distant recurrence by category (low, < 18;
intermediate, 18 to 30; high, >= 31) for treatment management among women
diagnosed with hormone receptor-positive, human epidermal growth factor receptor
2-negative, lymph node-negative breast cancer. Although non-Hispanic black (NHB)
women have worse prognosis compared with non-Hispanic white (NHW) women, the
equivalency of 21-gene RS across racial groups remains unknown. Patients and
Methods Using the Metropolitan Detroit Cancer Surveillance System, we identified
women who were diagnosed with hormone receptor-positive, human epidermal growth
factor receptor 2-negative, lymph node-negative invasive breast cancer between
2010 and 2014. Multinomial logistic regression was used to quantify racial
differences in 21-gene RS category. Results We identified 2,216 women (1,824 NHW
and 392 NHB) with invasive breast cancer who met clinical guidelines for and
underwent 21-gene RS testing. The mean RS was significantly higher in NHBs
compared with NHWs (19.3 v 17.0, respectively; P = .0003), where NHBs were more
likely to present with high-risk tumors compared with NHWs (14.8% v 8.3%,
respectively; P = .0004). These differences were limited to patients younger than
65 years at diagnosis, among whom NHBs had significantly higher RS compared with
NHWs (20 to 49 years: 23.6 v 17.3, respectively; P < .001 and 50 to 64 years:
19.6 v 17.4, respectively; P = .023). NHBs remained more likely to have high-risk
tumors compared with NHWs after adjusting for age, clinical stage, tumor grade,
and histology (odds ratio [OR], 1.75; 95% CI, 1.18 to 2.59). Conclusion NHBs who
met clinical criteria for 21-gene RS testing had tumors with higher estimated
risks of distant recurrence compared with NHWs. Further study is needed to
elucidate whether differences in recurrence are observed for these women, which
would have clinical implications for 21-gene RS calibration and treatment
recommendations in NHB patients.
PMID- 29341833
TI - Immune-Modified Response Evaluation Criteria In Solid Tumors (imRECIST): Refining
Guidelines to Assess the Clinical Benefit of Cancer Immunotherapy.
AB - Purpose Treating solid tumors with cancer immunotherapy (CIT) can result in
unconventional responses and overall survival (OS) benefits that are not
adequately captured by Response Evaluation Criteria In Solid Tumors (RECIST)
v1.1. We describe immune-modified RECIST (imRECIST) criteria, designed to better
capture CIT responses. Patients and Methods Atezolizumab data from clinical
trials in non-small-cell lung cancer, metastatic urothelial carcinoma, renal cell
carcinoma, and melanoma were evaluated. Modifications to imRECIST versus RECIST
v1.1 included allowance for best overall response after progressive disease (PD)
and changes in PD definitions per new lesions (NLs) and nontarget lesions.
imRECIST progression-free survival (PFS) did not count initial PD as an event if
the subsequent scan showed disease control. OS was evaluated using conditional
landmarks in patients whose PFS differed by imRECIST versus RECIST v1.1. Results
The best overall response was 1% to 2% greater, the disease control rate was 8%
to 13% greater, and the median PFS was 0.5 to 1.5 months longer per imRECIST
versus RECIST v1.1. Extension of imRECIST PFS versus RECIST v1.1 PFS was
associated with longer or similar OS. Patterns of progression analysis revealed
that patients who developed NLs without target lesion (TL) progression had a
similar or shorter OS compared with patients with RECIST v1.1 TL progression.
Patients infrequently experienced a spike pattern (TLs increase, then decrease)
but had longer OS than patients without TL reversion. Conclusion Evaluation of
PFS and patterns of response and progression revealed that allowance for TL
reversion from PD per imRECIST may better identify patients with OS benefit.
Progression defined by the isolated appearance of NLs, however, is not associated
with longer OS. These results may inform additional modifications to radiographic
criteria (including imRECIST) to better reflect efficacy with CIT agents.
PMID- 29341834
TI - Improvement in Overall Survival With Carfilzomib, Lenalidomide, and Dexamethasone
in Patients With Relapsed or Refractory Multiple Myeloma.
AB - Purpose In the ASPIRE study of carfilzomib, lenalidomide, and dexamethasone (KRd)
versus lenalidomide plus dexamethasone (Rd) in patients with relapsed or
refractory multiple myeloma, progression-free survival was significantly improved
in the carfilzomib group (hazard ratio, 0.69; two-sided P < .001). This
prespecified analysis reports final overall survival (OS) data and updated safety
results. Patients and Methods Adults with relapsed multiple myeloma (one to three
prior lines of therapy) were eligible and randomly assigned at a one-to-one ratio
to receive KRd or Rd in 28-day cycles until withdrawal of consent, disease
progression, or occurrence of unacceptable toxicity. After 18 cycles, all
patients received Rd only. Progression-free survival was the primary end point;
OS was a key secondary end point. OS was compared between treatment arms using a
stratified log-rank test. Results Median OS was 48.3 months (95% CI, 42.4 to 52.8
months) for KRd versus 40.4 months (95% CI, 33.6 to 44.4 months) for Rd (hazard
ratio, 0.79; 95% CI, 0.67 to 0.95; one-sided P = .0045). In patients receiving
one prior line of therapy, median OS was 11.4 months longer for KRd versus Rd; it
was 6.5 months longer for KRd versus Rd among patients receiving >= two prior
lines of therapy. Rates of treatment discontinuation because of adverse events
(AEs) were 19.9% (KRd) and 21.5% (Rd). Grade >= 3 AE rates were 87.0% (KRd) and
83.3% (Rd). Selected grade >= 3 AEs of interest (grouped terms; KRd v Rd)
included acute renal failure (3.8% v 3.3%), cardiac failure (4.3% v 2.1%),
ischemic heart disease (3.8% v 2.3%), hypertension (6.4% v 2.3%), hematopoietic
thrombocytopenia (20.2% v 14.9%), and peripheral neuropathy (2.8% v 3.1%).
Conclusion KRd demonstrated a statistically significant and clinically meaningful
reduction in the risk of death versus Rd, improving survival by 7.9 months. The
KRd efficacy advantage is most pronounced at first relapse.
PMID- 29341835
TI - Increasing Our Understanding of an Overlooked Public Health Epidemic: Traumatic
Brain Injuries in Women Subjected to Intimate Partner Violence.
PMID- 29341836
TI - A Cohort Study of Patient-Reported Outcomes and Healthcare Utilization in Acute
Myeloid Leukemia Patients Receiving Active Cancer Therapy in the Last Six Months
of Life.
AB - BACKGROUND: Evidence about the unique palliative care needs of patients with
acute myeloid leukemia (AML) is limited. Improving the care of these patients
will require a better understanding of their unmet needs, including symptom
burden at the end of life, and patterns of healthcare utilization. OBJECTIVE: To
describe AML patients' experiences in the last six months of life regarding
symptom burden, blood product utilization, and use of palliative care services.
METHODS: Exploratory analysis of prospectively collected patient-reported
outcomes and healthcare utilization data during the last six months of life among
33 AML patients who died during a longitudinal observational study. RESULTS:
Symptom burden, quality of life (QOL), and psychological distress worsened with
proximity to death. Of the 26 patients with utilization data, most (n = 24;
92.4%) were hospitalized in the last month of life, with 26.9% (n = 7) dying in
the intensive care unit. Patients required a median of 16 red blood cell
transfusions in the last six months of life, and those with a high transfusion
burden in the last month of life had a higher rate of in-hospital death (blood
transfusions: p < 0.01; platelet transfusions: p = 0.03). Only six patients
enrolled in hospice (23.1%). DISCUSSION: Patients with AML have marked symptoms
and QOL impairments that escalate in the final six months of life. Patients
entering the healthcare system for active cancer treatment are likely to continue
disease-oriented care until death. High rates of hospitalization and blood
product transfusion are a direct barrier to transitioning to hospice care.
PMID- 29341837
TI - Ocular Permeation of Topical Tazocin and Its Effectiveness in the Treatment of
Pseudomonas aeruginosa Induced Keratitis in Rabbits.
AB - PURPOSE: Pseudomonas aeruginosa is the most common causative organism for contact
lens-associated corneal ulcer and is commonly treated with fluoroquinolones. With
the emergence of resistant strains, it is important to investigate alternative
therapies. Despite well-established efficacy of tazocin against systemic
Pseudomonas infections, its topical use for the treatment of Pseudomonas
keratitis has not been described, hence this study was aimed to find the ocular
permeation of Tazocin and its efficacy in treating keratitis in rabbit eyes.
METHODS: We investigated the ocular permeation of topical tazocin after single
drop application in normal rabbit eyes by estimating piperacillin and tazobactam
concentrations in cornea, aqueous, and vitreous using a validated LC-MS/MS
method. Furthermore, we determined the efficacy of repeated dose administration
of tazocin against experimentally induced P. aeruginosa keratitis in rabbits in
comparison to moxifloxacin. To determine the efficacy, clinical examination,
histopathological examination, and estimation of bacterial load and inflammatory
cytokines in cornea were done. RESULTS: Significant corneal concentration of
piperacillin and tazobactam was detected in normal rabbit corneas after single
dose treatment with tazocin. In rabbits with Pseudomonas-induced keratitis,
topical tazocin caused significant clinical and histopathological improvement.
This improvement was associated with reduction in corneal bacterial load and
inflammatory cytokines. Compared to moxifloxacin 0.5%, tazocin treated group
showed greater clinical response which was associated with higher interleukin
(IL)-1beta, lower tumor necrosis factor (TNF)-alpha, a comparable level of IL-8,
greater reduction in corneal bacterial load, and lesser inflammatory cell
infiltration. CONCLUSION: Tazocin showed good ocular penetration and was
effective in treatment of Pseudomonas induced keratitis in rabbits.
PMID- 29341838
TI - Immobilization of cross-linked tannase enzyme on multiwalled carbon nanotubes and
its catalytic behavior.
AB - Immobilization of cross-linked tannase on pristine multiwalled carbon nanotubes
(MWCNT) was successfully performed. Cross-linking of tannase molecules was made
through glutaraldehyde. The immobilized tannase exhibited significantly improved
pH, thermal, and recycling stability. The optimal pH for both free and
immobilized tannase was observed at pH 5.0 with optimal operating temperature at
30 degrees C. Moreover, immobilized enzyme retained greater biocatalytic
activities upon 10 repeated uses compared to free enzyme in solution.
Immobilization of tannase was accomplished by strong hydrophobic interaction most
likely between hydrophobic amino acid moieties of the glutaraldehyde-cross-linked
tannase to the MWCNT.
PMID- 29341839
TI - Activation of Frataxin Protein Expression by Antisense Oligonucleotides Targeting
the Mutant Expanded Repeat.
AB - Friedreich's Ataxia (FA) is an inherited neurologic disorder caused by an
expanded GAA repeat within intron 1 of the frataxin (FXN) gene that reduces
expression of FXN protein. Agents that increase expression of FXN have the
potential to alleviate the disease. We previously reported that duplex RNAs
(dsRNAs) and antisense oligonucleotides (ASOs) complementary to the GAA repeat
could enhance expression of FXN protein. We now explore the potential of a
diverse group of chemically modified dsRNAs and ASOs to define the breadth of
repeat-targeted synthetic nucleic acids as a platform for therapeutic development
for FA. ASOs and dsRNAs can activate FXN protein expression in FA patient-derived
cell lines that possess varied numbers of GAA repeats. Increased FXN protein
expression was achieved by ASOs incorporating diverse chemical modifications with
low nanomolar potencies, suggesting substantial flexibility in choosing compounds
for further chemical optimization and animal studies. Our data encourage further
development of ASOs as agents to treat FA.
PMID- 29341840
TI - Surgical Site Infections after Open Reduction Internal Fixation for Trauma in Low
and Middle Human Development Index Countries: A Systematic Review.
AB - BACKGROUND: Musculoskeletal trauma represents a large source of morbidity in low
and middle human development index countries (LMHDICs). Open reduction and
internal fixation (ORIF) of traumatic long bone fractures definitively manages
these injuries and restores function when conducted safely and effectively.
Surgical site infections (SSIs) are a common complication of operative fracture
fixation, although the risks of infection are ill-defined in LMHDIC. PATIENTS AND
METHODS: This study reviewed systematically all studies describing SSI after ORIF
in LMDHICs. Studies were reviewed based on their qualitative characteristics,
after which a quantitative synthesis of weighted pooled infection rates based on
available patient-level data was performed to estimate published incidence of
SSI. RESULTS: Forty-two studies met criteria for qualitative review and 32
studies comprising 3,084 operations were included in the quantitative analysis.
Among 3,084 operations, the weighted pooled SSI rate was 6.4 infections per 100
procedures (95% confidence interval [CI] 4.6-8.2 infections per 100 procedures).
Higher rates of infection were noted among the sub-group of open fractures (95%
CI 13.9-23.0 infections per 100 procedures). Lower extremity injuries and
procedures utilizing intra-medullary nails also had slightly higher rates of
infection versus upper extremity procedures and other fixation devices.
CONCLUSIONS: Reported rates of SSI after ORIF are higher in LMHDICs, and may be
driven by high rates of infection in the sub-group of open fractures. This study
provides a baseline SSI rate obtained from literature produced from LMHDICs.
Infection rates are highly dependent on fracture sub-types.
PMID- 29341841
TI - Redefining Hypertension - Assessing the New Blood-Pressure Guidelines.
PMID- 29341842
TI - Purification and characterization of fibrinolytic protease from Bacillus
amyloliquefaciens MCC2606 and analysis of fibrin degradation product by MS/MS.
AB - A serine protease with preference for fibrin protein was purified and
characterized from Bacillus amyloliquefaciens MCC2606, isolated from dosa batter.
The protease was purified using ammonium sulfate precipitation, ion-exchange, and
gel filtration chromatography. The degradation activity of the protease toward
the fibrin was significantly higher compared with other protein substrates in the
study. The molecular weight of the CFR15-protease was estimated to be 32 kDa
based on SDS-PAGE. The purified enzyme exhibited both fibrinolytic and
fibrinogenolytic activity. The optimum pH and temperature for the activity of the
enzyme was found to be 10.5 and 45 degrees C. A significant inhibition was seen
with the protease inhibitors phenyl methyl sulphonyl fluoride and ethylene
diamine tetra acetic acid and the activity of the enzyme was enhanced in presence
of Mn2+. There was an observed increase in vitro activated partial thromboplastin
time and prothrombin time of both time and dose dependent study. Among the four
chains of fibrin, the beta-chain of fibrin appears to be the primary component
and site susceptible for CFR15-protease in early action as indicated by MS/MS
analysis of initial degradation products. These results indicated that the CFR15
protease have the potential to be an effective fibrinolytic agent.
PMID- 29341843
TI - Smart Care Based on Telemonitoring and Telemedicine for Type 2 Diabetes Care:
Multi-Center Randomized Controlled Trial.
AB - BACKGROUND: This study was performed to determine the effectiveness of the Smart
Care service on glucose control based on telemedicine and telemonitoring compared
with conventional treatment in patients with type 2 diabetes. MATERIALS AND
METHODS: This 24-week prospective multi-center randomized controlled trial
involved 338 adult patients with type 2 diabetes at four university hospitals in
South Korea. The patients were randomly assigned to a control group (group A, n =
113), a telemonitoring group (group B, n = 113), or a telemedicine group (group
C, n = 112). Patients in the telemonitoring group visited the outpatient clinic
regularly, accompanied by an additional telemonitoring service that included
remote glucose monitoring with automated patient decision support by text. Remote
glucose monitoring was identical in the telemedicine group, but assessment by
outpatient visits was replaced by video conferencing with an endocrinologist.
RESULTS: The adjusted net reductions in HbA1c concentration after 24 weeks were
similar in the conventional, telemonitoring, and telemedicine groups (-0.66% +/-
1.03% vs. -0.66% +/- 1.09% vs. -0.81% +/- 1.05%; p > 0.05 for each pairwise
comparison). Fasting glucose concentrations were lower in the telemonitoring and
telemedicine groups than in the conventional group. Rates of hypoglycemia were
lower in the telemedicine group than in the other two groups, and compliance with
medication was better in the telemonitoring and telemedicine than in the
conventional group. No serious adverse events were associated with telemedicine.
CONCLUSIONS: Telehealthcare was as effective as conventional care at improving
glycemia in patients with type 2 diabetes without serious adverse effects.
PMID- 29341844
TI - Empiric Antibiotics for Sepsis.
AB - BACKGROUND: Sepsis is life-threatening organ dysfunction caused by a dysregulated
host response to infection. Early recognition and treatment are the cornerstones
of management. METHODS: Review of the English-language literature. RESULTS: For
both sepsis and septic shock "antimicrobials [should be] be initiated as soon as
possible and within one hour" (Surviving Sepsis Campaign). The risk of
progression from severe sepsis to septic shock increases 8% for each hour before
antibiotics are started. Selection of antimicrobial agents is based on a
combination of patient factors, predicted infecting organism(s), and local
microbial resistance patterns. The initial drugs should have activity against
typical gram-positive and gram-negative causative micro-organisms. Anaerobic
coverage should be provided for intra-abdominal infections or others where
anaerobes are significant pathogens. Empiric antifungal or antiviral therapy may
be warranted. For patients with healthcare-associated infections, resistant micro
organisms will further complicate the choice of empiric antimicrobials.
Recommendations are given for specific infections. CONCLUSION: Early
administration of broad-spectrum antimicrobial drugs is one of the most
important, if not the most important, treatment for patients with sepsis or
septic shock. Drugs should be initiated as soon as possible, and the choice of
should take into account patient factors, common local pathogens, hospital
antibiograms and resistance patterns, and the suspected source of infection.
Antimicrobial agent therapy should be de-escalated as soon as possible.
PMID- 29341845
TI - Outside in - inside out. Creating focus on the patient - a vaccine company
perspective.
AB - Involving patients in the development of medicines and vaccines should result in
benefits to patients. The vaccine recipient is usually a healthy person. We
describe the rationale and implementation of a vaccine company's initiative to
encourage employees to identify with patients of the conditions prevented by the
vaccines they help to produce. The Voice of the Patient ("VoP"), begun in 2014,
is an educational programme directed at the 16,000 employees of a global vaccine
company. It engages employees through an understanding that they are all "vaccine
patients", and that they can make a difference by considering the impact of
decisions made in their day to day work. The initiative includes presentations
about vaccine-preventable diseases, global live webcasts with experts and
patients, employee visits to healthcare facilities in developing countries, and
the production of patient-focused sections in research publications. In a 2017
employee survey, 90% of respondents said they know how their daily work impacts
patients and they demonstrate focus on patients. We believe this is preliminary
evidence that, by supporting employee awareness of the impact of their individual
roles, VoP could be a model for a type of initiative that will contribute to
industry's continuing evolution towards more patient-centred healthcare.
PMID- 29341847
TI - Interview with Prof. Shannon N. Conley, James Madison University. Why Does Social
Context of Technology Matter?
PMID- 29341846
TI - Primary Intra-Medullary Nailing of Open Tibia Fractures Caused by Low-Velocity
Gunshots: Does Operative Debridement Increase Infection Rates?
AB - BACKGROUND: Although gunshot-induced extremity fractures are typically not
considered open fractures, there is controversy regarding wound management in the
setting of operative fixation to limit infection complications. Previous studies
have evaluated the need for a formal irrigation and debridement (I&D) prior to
intra-medullary nailing (IMN) of gunshot-induced femur fractures but none have
specifically evaluated tibias. By comparing primary IMN for tibial shaft
fractures caused by low-velocity firearms additionally treated with a formal
operative I&D (group 1) with those without an I&D (group 2), we sought to
identify whether there are: differences in treatment group infection rates;
particular fracture patterns more prone to infection; and patient characteristics
more prone to infections. PATIENTS AND METHODS: Retrospective cohort study at a
single level I trauma center of gunshot-induced tibial shaft fractures managed
primarily with IMN in 39 patients from October 1, 2008 to October 30, 2016. The
following were studied: demographics, follow-up, fracture characteristics, injury
management, and patient outcome. Fractures were categorized based on the
Orthopaedic Trauma Association (OTA) classification system for diaphyseal
tibia/fibula fractures. All patients had intravenous antibiotic agents at
presentation and received three days of post-operative intravenous antibiotic
agents per institutional protocol. RESULTS: In group 1, 6 of 23 patients (26.1%)
developed superficial infections and 4 of 23 patients (17.4%) developed deep
infections. In group 2, none of 16 patients (0%) developed superficial infections
and 1 patient (6.25%) developed a deep infection, making the total cohort
infection rate 28.2% (11/39). Superficial infections were associated with a
formal I&D whereas deep infections were not. Tobacco smokers and type 42-A
fractures had higher infection rates when treated with a formal I&D. CONCLUSION:
A formal debridement, followed by primary IMN in tibia fractures caused by low
velocity firearms is associated with an increased risk of superficial infection
that is well managed with antibiotic agents, but the incorporation of a
debridement does not affect rate of deep infection. A formal I&D during IMN
fixation should be avoided in patients that are smokers and have type 42-A tibia
fractures as these are factors associated with increased infection rates.
PMID- 29341848
TI - Protection of root apex meristem during stress responses.
AB - By regulating the levels of nitric oxide (NO) in a cell and tissue specific
fashion, Phytoglobins (Pgbs), plant hemoglobin-like proteins, interfere with many
NO-mediated pathways participating in developmental and stress-related responses.
Recent evidence reveals that one of the functions of Pgbs is to protect the root
apical meristem (RAM) from stress conditions by retaining the viability and
function of the quiescent center (QC), required to maintain the stem cells in an
undifferentiated state and ensure proper tissue patterning and root viability.
Based on this and other evidence, it is suggested that Pgbs regulate cell fate by
modulating NO homeostasis.
PMID- 29341849
TI - Factors affecting occlusion pressure and ischemic preconditioning.
AB - PURPOSE: To determine the effect of limb selection (upper/lower), cuff width
(small (6 cm)/medium (13 cm) upper; medium/large (18 cm) lower) and anthropometry
on arterial occlusion pressure (AOP) in ischemic preconditioning (IPC). METHODS:
Twenty athletes (10 females and 10 males) had surface anthropometry and dual x
ray absorptiometry (DXA) assessments before using Doppler ultrasound to confirm
AOP for each limb. Subsequently, 5 min of occlusion occurred, with near-infrared
spectroscopy (NIRS) measuring muscle oxygenation changes. Resultant AOP was
compared between sexes, limbs and cuff sizes using linear regression models.
RESULTS: Mean AOP was higher in the lower limbs than the upper limbs (161 +/- 18
vs. 133 +/- 12 mm Hg; p < .001), and with smaller cuffs in upper (161 +/- 16 vs.
133 +/- 12 mm Hg; p < .001), but not lower limbs (161 +/- 16 vs. 170 +/- 26 mm
Hg; p = .222). Sex and resting systolic blood pressure (SBP) accounted for 77%
(small cuff) to 83% (medium cuff) of variance in AOP for upper limbs, and 61%
(medium cuff) to 63% (large cuff) in lower limbs. Including anthropometry
accounted for 82% (small cuff) to 89% (medium cuff) and 78% (medium cuff) to 79%
(large cuff) of variance for upper and lower limbs, respectively. Adding DXA
variables improved the explained variance up to 83% (small cuff) to 91% (medium
cuff) and 79% (medium cuff) to 87% (large cuff) for upper and lower limbs,
respectively. NIRS data showed significantly greater tissue oxygenation changes
in upper versus lower limbs. CONCLUSIONS: The AOP in athletes is dependent on
limb occluded, sex, SBP, limb and cuff size, and body composition.
PMID- 29341850
TI - Clinical Inertia in a Randomized Trial of Telemedicine-Based Chronic Disease
Management: Lessons Learned.
AB - BACKGROUND: Treatment nonadherence and clinical inertia perpetuate poor
cardiovascular disease (CVD) risk factor control. Telemedicine interventions may
counter both treatment nonadherence and clinical inertia. INTRODUCTION: We
explored why a telemedicine intervention designed to reduce treatment
nonadherence and clinical inertia did not improve CVD risk factor control,
despite enhancing treatment adherence versus usual care. METHODS: In this
analysis of a randomized trial, we studied recipients of the 12-month
telemedicine intervention. This intervention comprised two nurse-administered
components: (1) monthly self-management education targeting improved treatment
adherence; and (2) quarterly medication management facilitation designed to
support treatment intensification by primary care (thereby reducing clinical
inertia). For each medication management facilitation encounter, we ascertained
whether patients met treatment goals, and if not, whether primary care
recommended treatment intensification following the encounter. We assessed
disease control associated with encounters, where intensification was/was not
recommended. RESULTS: We examined 455 encounters across 182 intervention
recipients (100% African Americans with type 2 diabetes). Even after accounting
for valid reasons for deferring intensification (e.g., treatment nonadherence),
intensification was not recommended in 67.5% of encounters in which hemoglobin
A1c was above goal, 72.5% in which systolic blood pressure was above goal, and
73.9% in which low-density lipoprotein cholesterol was above goal. In each
disease state, treatment intensification was more likely with poorer control.
CONCLUSIONS: Despite enhancing treatment adherence, this intervention was
unsuccessful in countering clinical inertia, likely explaining its lack of effect
on CVD risk factors. We identify several lessons learned that may benefit
investigators and healthcare systems.
PMID- 29341852
TI - Emissions of organic compounds from produced water ponds II: Evaluation of flux
chamber measurements with inverse-modeling techniques.
AB - : In this study, the authors apply two different dispersion models to evaluate
flux chamber measurements of emissions of 58 organic compounds, including C2-C11
hydrocarbons and methanol, ethanol, and isopropanol from oil- and gas-produced
water ponds in the Uintah Basin. Field measurement campaigns using the flux
chamber technique were performed at a limited number of produced water ponds in
the basin throughout 2013-2016. Inverse-modeling results showed significantly
higher emissions than were measured by the flux chamber. Discrepancies between
the two methods vary across hydrocarbon compounds and are largest in alcohols due
to their physical chemistries. This finding, in combination with findings in a
related study using the WATER9 wastewater emission model, suggests that the flux
chamber technique may underestimate organic compound emissions, especially
alcohols, due to its limited coverage of the pond area and alteration of
environmental conditions, especially wind speed. Comparisons of inverse-model
estimations with flux chamber measurements varied significantly with the
complexity of pond facilities and geometries. Both model results and flux chamber
measurements suggest significant contributions from produced water ponds to total
organic compound emission from oil and gas productions in the basin.
IMPLICATIONS: This research is a component of an extensive study that showed
significant amount of hydrocarbon emissions from produced water ponds in the
Uintah Basin, Utah. Such findings have important meanings to air quality
management agencies in developing control strategies for air pollution in oil and
gas fields, especially for the Uintah Basin in which ozone pollutions frequently
occurred in winter seasons.
PMID- 29341853
TI - Influence of high heat load on flow and containment of an inclined air-curtain
(IAC) fume hood.
AB - The inclined air-curtain (IAC) fume hood has been reported to have "almost null
leakage"[1] at low suction flow rates when operated at regular temperatures.
However, previous research has not investigated the performance or optimized
operating parameters when a high heat load is used in the IAC fume hood. For the
present work, the effects of a high heat load on the flow field and contaminant
leakage characteristics of the IAC fume hood were examined. The heat load was
supplied to an IAC hood according to the standard method of EN14175-7:2012. The
laser-assisted smoke flow visualization technique was employed to identify the
characteristic flow patterns. The standard tracer-gas concentration test method
(EN14175-3:2003) was used to examine the leakage levels of the IAC fume hood
under static conditions, sash movement, and simulated walk-by conditions. When
the IAC fume hood was operated at a high heat load, the static test results
showed negligibly small leakage levels at a face velocity greater than or equal
to only 0.19 m/s (37.4 ft/min). The sash movement and simulated walk-by test
results showed that to obtain negligibly small leakage levels at high heat load
operation, the IAC fume hood required a face velocity greater than or equal to
0.32 m/s (63 ft/min). In addition, the IAC fume hood exhibited a superior hood
containment performance with low energy consumption when compared with
conventional fume hoods operated at a high heat load.
PMID- 29341851
TI - Underutilization of Supplemental Magnetic Resonance Imaging Screening Among
Patients at High Breast Cancer Risk.
AB - BACKGROUND: Women at high lifetime breast cancer risk may benefit from
supplemental breast magnetic resonance imaging (MRI) screening, in addition to
routine mammography screening for earlier cancer detection. MATERIALS AND
METHODS: We performed a cross-sectional study of 422,406 women undergoing routine
mammography screening across 86 Breast Cancer Surveillance Consortium (BCSC)
facilities during calendar year 2012. We determined availability and use of on
site screening breast MRI services based on woman-level characteristics,
including >20% lifetime absolute risk using the National Cancer Institute risk
assessment tool. Multivariate analyses were performed to determine
sociodemographic characteristics associated with on-site screening MRI use.
RESULTS: Overall, 43.9% (2403/5468) of women at high lifetime risk attended a
facility with on-site breast MRI screening availability. However, only 6.6%
(158/2403) of high-risk women obtained breast MRI screening within a 2-year
window of their screening mammogram. Patient factors associated with on-site MRI
screening use included younger (<40 years) age (odds ratio [OR] = 2.39, 95%
confidence interval [CI]: 1.34-4.21), family history (OR = 1.72, 95% CI: 1.13
2.63), prior breast biopsy (OR = 2.09, 95% CI: 1.22-3.58), and postsecondary
education (OR = 2.22, 95% CI: 1.04-4.74). CONCLUSIONS: While nearly half of women
at high lifetime breast cancer risk undergo routine screening mammography at a
facility with on-site breast MRI availability, supplemental breast MRI remains
widely underutilized among those who may benefit from earlier cancer detection.
Future studies should evaluate whether other enabling factors such as formal risk
assessment and patient awareness of high lifetime breast cancer risk can mitigate
the underutilization of supplemental screening breast MRI.
PMID- 29341854
TI - Separation of brown carbon from black carbon for IMPROVE and Chemical Speciation
Network PM2.5 samples.
AB - : The replacement of the Desert Research Institute (DRI) model 2001 with model
2015 thermal/optical analyzers (TOAs) results in continuity of the long-term
organic carbon (OC) and elemental carbon (EC) database, and it adds optical
information with no additional carbon analysis effort. The value of
multiwavelength light attenuation is that light absorption due to black carbon
(BC) can be separated from that of brown carbon (BrC), with subsequent
attribution to known sources such as biomass burning and secondary organic
aerosols. There is evidence of filter loading effects for the 25% of all samples
with the highest EC concentrations based on the ratio of light attenuation to EC.
Loading corrections similar to those used for the seven-wavelength aethalometer
need to be investigated. On average, nonurban Interagency Monitoring of PROtected
Visual Environments (IMPROVE) samples show higher BrC fractions of short
wavelength absorption than urban Chemical Speciation Network (CSN) samples, owing
to greater influence from biomass burning and aged aerosols, as well as to higher
primary BC contributions from engine exhaust at urban sites. Sequential samples
taken during an Everglades National Park wildfire demonstrate the evolution from
flaming to smoldering combustion, with the BrC fraction increasing as smoldering
begins to dominate the fire event. IMPLICATIONS: The inclusion of seven
wavelengths in thermal/optical carbon analysis of speciated PM2.5 (particulate
matter with an aerodynamic diameter <=2.5 MUm) samples allows contributions from
biomass burning and secondary organic aerosols to be estimated. This separation
is useful for evaluating control strategy effectiveness, identifying exceptional
events, and determining natural visibility conditions.
PMID- 29341855
TI - Probabilistic assessment of the potential indoor air impacts of vent-free gas
heating appliances in energy-efficient homes in the United States.
AB - : Use of vent-free gas heating appliances for supplemental heating in U.S. homes
is increasing. However, there is currently a lack of information on the potential
impact of these appliances on indoor air quality for homes constructed according
to energy-efficient and green building standards. A probabilistic analysis was
conducted to estimate the impact of vent-free gas heating appliances on indoor
air concentrations of carbon monoxide (CO), nitrogen dioxide (NO2), carbon
dioxide (CO2), water vapor, and oxygen in "tight" energy-efficient homes in the
United States. A total of 20,000 simulations were conducted for each Department
of Energy (DOE) heating region to capture a wide range of home sizes, appliance
features, and conditions, by varying a number of parameters, e.g., room volume,
house volume, outdoor humidity, air exchange rates, appliance input rates
(Btu/hr), and house heat loss factors. Predicted airborne levels of CO were below
the U.S. Environmental Protection Agency (EPA) standard of 9 ppm for all modeled
cases. The airborne concentrations of NO2 were below the U.S. Consumer Product
Safety Commission (CPSC) guideline of 0.3 ppm and the Health Canada benchmark of
0.25 ppm in all cases and were below the World Health Organization (WHO) standard
of 0.11 ppm in 99-100% of all cases. Predicted levels of CO2 were below the
Health Canada standard of 3500 ppm for all simulated cases. Oxygen levels in the
room of vent-free heating appliance use were not significantly reduced. The great
majority of cases in all DOE regions were associated with relative humidity (RH)
levels from all indoor water vapor sources that were less than the EPA
recommended 70% RH maximum to avoid active mold and mildew growth. The conclusion
of this investigation is that when installed in accordance with the
manufacturer's instructions, vent-free gas heating appliances maintain acceptable
indoor air quality in tight energy-efficient homes, as defined by the standards
referenced in this report. IMPLICATIONS: Probabilistic modeling of indoor air
concentrations of carbon monoxide (CO), nitrogen dioxide (NO2), carbon dioxide
(CO2), water vapor, and oxygen associated with use of vent-free gas heating
appliances provides new data indicating that uses of these devices are consistent
with acceptable indoor air quality in "tight" energy-efficient homes in the
United States. This study will provide authoritative bodies such as the
International Code Council with definitive information that will assist in the
development of future versions of national building codes, and will provide
evaluation of the performance of unvented gas heating products in energy
conservation homes.
PMID- 29341857
TI - Development of visibility forecasting modeling framework for the Lower Fraser
Valley of British Columbia using Canada's Regional Air Quality Deterministic
Prediction System.
AB - : Visibility degradation, one of the most noticeable indicators of poor air
quality, can occur despite relatively low levels of particulate matter when the
risk to human health is low. The availability of timely and reliable visibility
forecasts can provide a more comprehensive understanding of the anticipated air
quality conditions to better inform local jurisdictions and the public. This
paper describes the development of a visibility forecasting modeling framework,
which leverages the existing air quality and meteorological forecasts from
Canada's operational Regional Air Quality Deterministic Prediction System
(RAQDPS) for the Lower Fraser Valley of British Columbia. A baseline model (GM
IMPROVE) was constructed using the revised IMPROVE algorithm based on unprocessed
forecasts from the RAQDPS. Three additional prototypes (UMOS-HYB, GM-MLR, GM-RF)
were also developed and assessed for forecast performance of up to 48 hr lead
time during various air quality and meteorological conditions. Forecast
performance was assessed by examining their ability to provide both numerical and
categorical forecasts in the form of 1-hr total extinction and Visual Air Quality
Ratings (VAQR), respectively. While GM-IMPROVE generally overestimated extinction
more than twofold, it had skill in forecasting the relative species contribution
to visibility impairment, including ammonium sulfate and ammonium nitrate. Both
statistical prototypes, GM-MLR and GM-RF, performed well in forecasting 1-hr
extinction during daylight hours, with correlation coefficients (R) ranging from
0.59 to 0.77. UMOS-HYB, a prototype based on postprocessed air quality forecasts
without additional statistical modeling, provided reasonable forecasts during
most daylight hours. In terms of categorical forecasts, the best prototype was
approximately 75 to 87% correct, when forecasting for a condensed three-category
VAQR. A case study, focusing on a poor visual air quality yet low Air Quality
Health Index episode, illustrated that the statistical prototypes were able to
provide timely and skillful visibility forecasts with lead time up to 48 hr.
IMPLICATIONS: This study describes the development of a visibility forecasting
modeling framework, which leverages the existing air quality and meteorological
forecasts from Canada's operational Regional Air Quality Deterministic Prediction
System. The main applications include tourism and recreation planning, input into
air quality management programs, and educational outreach. Visibility forecasts,
when supplemented with the existing air quality and health based forecasts, can
assist jurisdictions to anticipate the visual air quality impacts as perceived by
the public, which can potentially assist in formulating the appropriate air
quality bulletins and recommendations.
PMID- 29341856
TI - KIX domain of AtMed15a, a Mediator subunit of Arabidopsis, is required for its
interaction with different proteins.
AB - Med15 is an important subunit of Mediator Tail module and is characterized by a
KIX domain present towards amino terminal. In yeast and metazoans, Med15 KIX
domain has been found to interact with various transcription factors regulating
several processes including carbohydrate metabolism, lipogenesis, stress response
and multidrug resistance. Mechanism of Med15 functioning in Arabidopsis is
largely unknown. In this study, interactome of KIX domain of Arabidopsis Med15,
AtMed15a, was characterized. We found 45 proteins that interact with AtMed15a KIX
domain, including 11 transcription factors, 3 single strand nucleic acid-binding
proteins and 1 splicing factor. The third helix of the KIX domain was found to be
involved in most of the interactions. Mapping of the regions participating in the
interactions revealed that the activation domain of a transcription factor, UKTF1
interacted with AtMed15a KIX domain. Thus, our results suggest that in
Arabidopsis, activation domain of transcription factors target KIX domain of
AtMed15a for their transcriptional responses.
PMID- 29341858
TI - Respiratory assessment of refractory ceramic fibers in a heating technician
population.
AB - Refractory ceramic fibers (RCF) have been extensively used for insulation in
condensing boilers. The aim of this study was to evaluate the respiratory
exposure to these fibers among maintenance heating technicians. We first created
a working group (Carsat Brittany and Finistere Occupational Health Services) and
carried out a sampling strategy. Atmospheric measurements were done during work
tasks, and filters were analyzed by phase contrast microscopy (PCM) and scanning
electron microscopy (SEM) in French approved laboratories. Four companies were
included for a total of 15 days of work. During those 15 workdays, 12 SEM and 21
PCM samples were taken and analyzed. The phase contrast microscopy and SEM
average results were 0.04 and 0.004 fibers/cm3, respectively. In conclusion, the
study confirms heating technician RCF respiratory exposure during maintenance
work for both condensation gas boilers and atmospheric boilers. Collective and
individual prevention measures should be implemented along with appropriate
medical follow-up.
PMID- 29341859
TI - An indoor air quality evaluation in a residential retrofit project using spray
polyurethane foam.
AB - Understanding of indoor air quality (IAQ) during and after spray polyurethane
foam (SPF) application is essential to protect the health of both workers and
building occupants. Previous efforts such as field monitoring, micro
chamber/spray booth emission studies, and fate/transport modeling have been
conducted to understand the chemical exposure of SPF and guide risk mitigation
strategies. However, each type of research has its limitation and can only reveal
partial information on the relationship between SPF and IAQ. A comprehensive
study is truly needed to integrate the experimental design and analytical testing
methods in the field/chamber studies with the mathematical tools employed in the
modeling studies. This study aims to bridge this gap and provide a more
comprehensive understanding on the impact of SPF to IAQ. The field sampling plan
of this research aims to evaluate the airborne concentrations of methylene
diphenyl diisocyanate (MDI), formaldehyde, acetaldehyde, propionaldehyde, tris(1
chlor-2-propyl)phosphate (TCPP), trans-1-chloro-3,3,3-trifluoropropene
(SolsticeTM), and airborne particles. Modifications to existing MDI sampling and
analytical methods were made so that level of quantification was improved. In
addition, key fate and transport modeling input parameters such as air changes
per hour and airborne particle size distribution were measured. More importantly,
TCPP accumulation onto materials was evaluated, which is important to study the
fate and transport of semi-volatile organic compounds. The IAQ results showed
that after spray application was completed in the entire building, airborne
concentrations decreased for all chemicals monitored. However, it is our
recommendation that during SPF application, no one should return to the
application site without proper personal protection equipment as long as there
are active spray activities in the building. The comparison between this field
study and a recent chamber study proved surface sorption and particle deposition
is an important factor in determining the fate of airborne TCPP. The study also
suggests the need for further evaluation by employing mathematical models,
proving the data generated in this work as informative to industry and the
broader scientific community.
PMID- 29341860
TI - Risk management of free radicals involved in air travel syndromes by
antioxidants.
AB - Frequent air travelers and airplane pilots may develop various types of
illnesses. The environmental risk factors associated with air travel syndromes
(ATS) or air travel-related adverse health outcomes raised concerns and need to
be assessed in the context of risk management and public health. Accordingly, the
aim of the present review was to determine ATS, risk factors, and mechanisms
underlying ATS using scientific data and information obtained from Medline,
Toxline, and regulatory agencies. Additional information was also extracted from
websites of organizations, such as the International Air Transport Association
(IATA), International Association for Medical Assistance to Travelers (IAMAT),
and International Civil Aviation Organization (ICAO). Air travelers are known to
be exposed to environmental risk factors, including circadian rhythm disruption,
poor cabin air quality, mental stress, high altitude conditions, hormonal
dysregulation, physical inactivity, fatigue, biological infections, and alcoholic
beverage consumption. Consequences of ATS attributed to air travel include sleep
disturbances (e.g., insomnia), mental/physical stress, gastrointestinal
disorders, respiratory diseases, circulatory-related dysfunction, such as cardiac
arrest and thrombosis and, at worst, mechanical and terrorism-related airplane
crashes. Thus safety measures in the cabin before or after takeoff are undertaken
to prevent illnesses or accidents related to flight. In addition, airport
quarantine systems are strongly recommended to prepare for any ultimate adverse
circumstances. Routine monitoring of environmental risk factors also needs to be
considered. Frequently, the mechanisms underlying these adverse manifestations
involve free radical generation. Therefore, antioxidant supplementation may help
to reduce or prevent adverse outcomes by mitigating health risk factors
associated with free radical generation.
PMID- 29341861
TI - Genome-wide survey reveals dynamic effects of folate supplement on DNA
methylation and gene expression during C2C12 differentiation.
AB - Folic acid supplements taken during pregnancy can prevent neural tube defects and
other developmental abnormalities. Here, we explored the effects of folate
supplementation on gene expression and DNA methylation during C2C12
differentiation. Based on the folic acid concentration, this study comprised
three groups: low folate (L), normal folate (N), and high-folate supplement (H).
Our analyses revealed that differentiation and the mRNA expression of the gene
myogenin in C2C12 cell were enhanced by folic acid; however, the overall
methylation percentage in myogenin promoter between different treatment groups
was not significantly different ( P > 0.05). The results of MeDIP-chip showed
that hundreds of differentially methylated regions (DMRs) were identified between
every two groups in both promoter and CpG islands, respectively. Genes with DMRs
between N and L groups were mainly enriched in the processes of cell
differentiation and cell development, whereas those with DMRs between H and N
groups were frequently enriched in cellular process/cycle and cell metabolic
processes. In addition, correlation analysis between methylation profile and
expression profile revealed that some genes were regulated by methylation status
directly. Together, these analyses suggest that folate deficiency and
supplementation can influence the differentiation, genome-wide DNA methylation
level and the expression of myogenesis-related genes including myogenin in the
C2C12 cell line.
PMID- 29341862
TI - Identification of three genetic variants as novel susceptibility loci for body
mass index in a Japanese population.
AB - Recent genome-wide association studies have identified various obesity or
metabolic syndrome (MetS) susceptibility loci. However, most studies were
conducted in a cross-sectional manner. To address this gap, we performed a
longitudinal exome-wide association study to identify susceptibility loci for
obesity and MetS in a Japanese population. We traced clinical data of 6,022
Japanese subjects who had annual health check-ups for several years (mean follow
up period, 5 yr) and genotyped ~244,000 genetic variants. The association of
single nucleotide polymorphisms (SNPs) with body mass index (BMI) or the
prevalence of obesity and MetS was examined in a generalized estimating equation
model. Our longitudinal exome-wide association studies detected 21 BMI- and five
MetS-associated SNPs (false discovery rate, FDR <0.01). Among these SNPs, 16 have
not been previously implicated as determinants of BMI or MetS. Cross-sectional
data for obesity- and MetS-related phenotypes in 7,285 Japanese subjects were
examined in a replication study. Among the 16 SNPs, three ( rs9491140 ,
rs145848316 , and rs7863248 ) were related to BMI in the replication cohort ( P <
0.05). In conclusion, three SNPs [ rs9491140 of NKAIN2 (FDR = 0.003, P = 1.9 * 10
5), rs145848316 of KMT2C (FDR = 0.007, P = 4.5 * 10-5), and rs7863248 of AGTPBP1
(FDR = 0.006, P = 4.2 * 10-5)] were newly identified as susceptibility loci for
BMI.
PMID- 29341863
TI - Distinct gene signatures predict insulin resistance in young mice with high fat
diet-induced obesity.
AB - Highly inbred C57BL/6 mice show wide variation in their degree of insulin
resistance in response to diet-induced obesity even though they are almost
genetically identical. Here we employed transcriptional profiling by RNA
sequencing (RNA-Seq) of visceral adipose tissue (VAT) and liver in young mice to
determine how gene expression patterns correlate with the later development of
high-fat diet (HFD)-induced insulin resistance in adulthood. To accomplish this
goal, we partially removed and banked tissues from pubertal mice. Mice
subsequently received HFD followed by metabolic phenotyping to identify two well
defined groups of mice with either severe or mild insulin resistance. The
remaining tissues were collected at study termination. We then applied RNA-Seq to
generate transcriptome profiles associated with worsened insulin resistance
before and after the initiation of HFD. We found 244 up- and 109 downregulated
genes in VAT of the most insulin-resistant mice even before HFD exposure.
Downregulated genes included serine protease inhibitor, major urinary protein,
and complement genes; upregulated genes represented mostly muscle constituents.
These gene families were also differentially expressed in VAT of mice with high
or low insulin resistance after HFD. Inflammatory genes predicted insulin
resistance in liver, but not in VAT. In contrast, when we compared VAT of all
mice before and after HFD, differentially expressed genes were predominantly
composed of immune response genes. These data show a distinct set of gene
transcripts in young mice correlates with the severity of insulin resistance in
adulthood, providing insight into the pathogenesis of insulin resistance in early
life.
PMID- 29341864
TI - Comparison of acute kidney injury of different etiology reveals in-common
mechanisms of tissue damage.
AB - Acute kidney injury (AKI) is a syndrome of reduced glomerular filtration rate and
urine production caused by a number of different diseases. It is associated with
renal tissue damage. This tissue damage can cause tubular atrophy and
interstitial fibrosis that leads to nephron loss and progression of chronic
kidney disease (CKD). This review describes the in-common mechanisms behind
tissue damage in AKI caused by different underlying diseases. Comparing six high
quality microarray studies of renal gene expression after AKI in disease models
(gram-negative sepsis, gram-positive sepsis, ischemia-reperfusion, malignant
hypertension, rhabdomyolysis, and cisplatin toxicity) identified 5,254
differentially expressed genes in at least one of the AKI models; 66% of genes
were found only in one model, showing that there are unique features to AKI
depending on the underlying disease. There were in-common features in the form of
four genes that were differentially expressed in all six models, 49 in at least
five, and 215 were found in common between at least four models. Gene ontology
enrichment analysis could be broadly categorized into the injurious processes
hypoxia, oxidative stress, and inflammation, as well as the cellular outcomes of
cell death and tissue remodeling in the form of epithelial-to-mesenchymal
transition. Pathway analysis showed that MYC is a central connection in the
network of activated genes in-common to AKI, which suggests that it may be a
central regulator of renal gene expression in tissue injury during AKI. The
outlining of this molecular network may be useful for understanding progression
from AKI to CKD.
PMID- 29341865
TI - Evidence of genetic predisposition for metabolically healthy obesity and
metabolically obese normal weight.
AB - Obesity has evolved into a global pandemic that constitutes a major threat to
public health. The majority of obesity-related health care costs are due to
cardiometabolic complications, such as insulin resistance, dyslipidemia, and
hypertension, which are risk factors for Type 2 diabetes and cardiovascular
disease. However, many obese individuals, often called metabolically healthy
obese (MHO), seem to be protected from these cardiometabolic complications.
Conversely, there is a group of individuals who suffer from cardiometabolic
complications despite being of normal weight; a condition termed metabolically
obese normal weight (MONW). Recent large-scale genomic studies have provided
evidence that a number of genetic variants show an association with increased
adiposity but a favorable cardiometabolic profile, an indicator for the genetic
basis of the MHO and MONW phenotypes. Many of these loci are located in or near
genes that implicate pathways involved in adipogenesis, fat distribution, insulin
signaling, and insulin resistance. It has been suggested that a threshold for
subcutaneous adipose tissue expandability may be at play in the manifestation of
MHO and MONW, where expiry of adipose tissue storage capacity could lead to
ectopic lipid accumulation in non-adipose tissues such as liver, muscle, heart,
and pancreatic beta cells. Understanding the genetic aspects of the mechanisms
that underpin MHO and MONW is crucial to define appropriate public health action
points and to develop effective intervention measures.
PMID- 29341866
TI - Identifying low-grade cellular rejection after heart transplantation in children
by using gene expression profiling.
AB - Endomyocardial biopsy (EMB) remains the gold standard for detecting rejection
after heart transplantation but is costly and invasive. This study aims to
distinguish no rejection (0R) from low-grade rejection (1R/2R) after heart
transplantation in children by using global gene expression profiling in blood. A
total of 106 blood samples with corresponding EMB from 18 children who underwent
heart transplantation from 2011 to 2014 were analyzed (18
baseline/pretransplantation samples, 88 EMB samples). Corresponding rejection
grades for each blood sample were 0R in 39% (34/88), 1R in 51% (45/88), and 2R in
10% (9/88). mRNA from each sample was sequenced. Differential expression analysis
was performed at the gene level. A k-nearest neighbor (kNN) analysis was applied
to the most differentially expressed (DE) genes to identify rejection after
transplantation. Mean age at transplantation was 10.0 +/- 5.4 yr. Expression of B
cell and T cell receptor sequences was used to measure the effect of
posttransplantation immunosuppression. Follow-up samples had lower levels of
immunoglobulin gene families compared with pretransplantation ( P < 3E-5) (lower
numbers of activated B cells). T cell receptor alpha and beta gene families had
decreased expression in 0R samples compared with pretransplantation ( P < 4E-5)
but recovered to near baseline levels in 1R/2R samples. kNN using the most DE
gene (MKS1) and k = 9 nearest neighbors correctly identified 83% (73/88) of 1R/2R
compared with 0R by leave-one-out cross validation. Using a genomic approach we
can distinguish low-grade cellular allograft rejection (1R/2R) from no rejection
(0R) after heart transplantation in children despite a wide age range.
PMID- 29341868
TI - Transcriptional evidence for cross talk between JA and ET or SA during root-knot
nematode invasion in tomato.
AB - studies have demonstrated that jasmonic acid (JA) reduces root-knot nematode
(RKN) infections in tomato plants. RKN invasion is sensed by roots, and root
derived JA signaling activates systemic defense responses, though this is poorly
understood. Here, we investigate variations in the RKN-induced transcriptome in
scion phloem between two tomato plant grafts: CM/CM ( Lycopersicum esculentum
Mill. cv. Castlemart) and CM/ spr2 (a JA-deficient mutant). A total of 8,716
genes were differentially expressed in the scion phloem of the plants with JA
deficient rootstock via RNA sequencing. Among these genes, 535 upregulated and
153 downregulated genes with high copy numbers were identified as significantly
differentially expressed. Among them, 34 predicted transcription factor genes
were identified. Additionally, we used real-time quantitative PCR to analyze the
expression patterns of 42 genes involved in the JA, ethylene, or salicylic acid
pathway in phloem under RKN infection. The results suggested that in the absence
of JA signaling, the ET signaling pathway is enhanced after RKN infection;
however, alterations in the SA signaling pathway were not observed.
PMID- 29341867
TI - Genetic and microbiome influence on lipid metabolism and dyslipidemia.
AB - Disruption in the metabolism of lipids is broadly classified under dyslipidemia
and relates to the concentration of lipids in the blood. Dyslipidemia is a
predictor of cardio-metabolic disease including obesity. Traditionally, the large
interindividual variation has been related to genetic factors and diet. Genome
wide association studies have identified over 150 loci related to abnormal lipid
levels, explaining ~40% of the total variation. Part of the unexplained variance
has been attributed to environmental factors including diet, but the extent of
the dietary contribution remains unquantified. Furthermore, other factors are
likely to influence lipid metabolism including the gut microbiome, which plays an
important role in the digestion of different dietary components including fats
and polysaccharides. Here we describe the contributing role of host genetics and
the gut microbiome to dyslipidemia and discuss the potential therapeutic
implications of advances in understanding the gut microbiome to the treatment of
dyslipidemia.
PMID- 29341870
TI - Easy or Hard: It Makes a Tremendous Difference.
PMID- 29341869
TI - A Report of the 24th Annual Congress on Women's Health-Workshop on Transforming
Women's Health: From Research to Practice.
AB - Sex and gender are critical contributors to overall health and disease, and
considering both in research informs the development of prevention strategies and
treatment interventions for both men and women. The National Institutes of Health
(NIH) Office of Research on Women's Health sponsored a preconference workshop on
this topic at the 24th Annual Women's Health Congress, which was held in Crystal
City, VA, in April 2016. The workshop featured presentations by NIH intramural
and extramural scientists who presented data on a variety of topics including
polycystic kidney disease, vaccine protection, depression, drug addiction, and
cardiovascular disease. In this publication, we discuss the major points of each
presentation and demonstrate the importance of considering sex and gender in
biomedical research.
PMID- 29341872
TI - A CqFerritin protein inhibits white spot syndrome virus infection via regulating
iron ions in red claw crayfish Cherax quadricarinatus.
AB - It is well known that iron is an essential element for all living organism. The
intracellular iron availability is also important for the host's innate immune
response to various pathogens, in which the iron homeostasis can be regulated by
ferritin due to its iron storage property. In this study, a full-length cDNA
sequence of ferritin (named as CqFerritin) was identified with 1410 bp from red
claw crayfish Cherax quadricarinatus, which contained an open reading frame of
513 bp, encoding 170 amino acids with a conserved ferritin domain. Tissue
distribution analysis demonstrated that CqFerritin was widely expressed in
various tissues with high presence in haemocyte, haematopoietic tissue (Hpt) and
heart, while lowest expression in hepatopancreas. In addition, loss-of-function
of CqFerritin by gene silencing resulted in significantly higher expression of an
envelope protein VP28 of white spot syndrome virus (WSSV) in red claw crayfish
Hpt cell cultures, indicating the potential antiviral response of CqFerritin. To
further explore the effect on WSSV replication by CqFerritin, recombinant
CqFerritin protein (rCqFerritin) was transfected into Hpt cells followed by WSSV
infection. Importantly, the replication of WSSV was obviously decreased in Hpt
cells if transfected with rCqFerritin protein, suggesting that CqFerritin had
clearly negative effect on WSSV infection. Furthermore, intracellular
accumulation of iron ions was found to promote the WSSV replication in a dose
dependent manner, illustrating that the iron level regulated by CqFerritin was
likely to be vital for WSSV infection in red claw crayfish. Taken together, these
data suggest that CqFerritin plays an important role in immune defense against
WSSV infection in a crustacean C. quadricarinatus.
PMID- 29341873
TI - Differences in heart rate reserve of similar physical activities during work and
in leisure time - A study among Danish blue-collar workers.
AB - Recent studies suggest that while leisure-time physical activity (LTPA) promotes
general health, engaging in occupational physical activity (OPA) may have
negative health consequences. It has been hypothesized that the different health
effects from OPA and LTPA can be explained by differences in physical activity
(PA) intensity in these two domains. To assess the intensity of OPA and LTPA, we
aimed to study the percentage heart rate reserve (%HRR) during similar types of
OPA and LTPA during workdays. Data from the NOMAD study on Danish blue-collar
workers (n=124) with objective measurements of PA (using accelerometers) and
heart rate (using heart rate monitors) for 4 workdays were analysed. Activities
of sitting, standing, moving, walking, and stair climbing were identified and
%HRR in each of these activities was determined for work and leisure. %HRR was
significantly higher during OPA than LTPA. These differences were more pronounced
in men than in women. Although not statistically significant in the fully
adjusted model, we found indications that these differences were more pronounced
in those with low compared to high fitness. To our knowledge, this is the first
study with objective measurements showing that %HRR is higher during the same
gross-body postural activities when performed at work compared to leisure-time
during workdays. This elevated intensity may help explaining the negative health
consequences of engagement in high levels of OPA. Future guidelines should
distinguish OPA from LTPA, possibly by advising workers to remain active during
their leisure time, in particular when they are highly active at work.
PMID- 29341874
TI - Validation of an ICD code for accurately identifying emergency department
patients who suffer an out-of-hospital cardiac arrest.
AB - AIM: International classification of disease (ICD-9) code 427.5 (cardiac arrest)
is utilized to identify cohorts of patients who suffer out-of-hospital cardiac
arrest (OHCA), though the use of ICD codes for this purpose has never been
formally validated. We sought to validate the utility of ICD-9 code 427.5 by
identifying patients admitted from the emergency department (ED) after OHCA.
METHODS: Adult visits to a single ED between January 2007 and July 2012 were
retrospectively examined and a keyword search of the electronic medical record
(EMR) was used to identify patients. Cardiac arrest was confirmed; and ICD-9
information and location of return of spontaneous circulation (ROSC) were
collected. Separately, the EMR was searched for patients who received ICD-9 code
427.5. The kappa coefficient (kappa) was calculated, as was the sensitivity and
specificity of the code for identifying OHCA. RESULTS: The keyword search
identified 1717 patients, of which 385 suffered OHCA and 333 were assigned the
code 427.5. The agreement between ICD-9 code and cardiac arrest was excellent
(kappa = 0.895). The ICD-9 code 427.5 was both specific (99.4%) and sensitive
(86.5%). Of the 52 cardiac arrests that were not identified by ICD-9 code, 33%
had ROSC before arrival to the ED. When searching independently on ICD-9 code,
347 patients with ICD-9 code 427.5 were found, of which 320 were "true" arrests.
This yielded a positive predictive value of 92% for ICD-9 code 427.5 in
predicting OHCA. CONCLUSIONS: ICD-9 code 427.5 is sensitive and specific for
identifying ED patients who suffer OHCA with a positive predictive value of 92%.
PMID- 29341875
TI - Beyond JAAD April 2018: Articles of interest to dermatologists from the
nondermatologic literature.
PMID- 29341876
TI - Probing and characterizing the high specific sequences of ssDNA aptamer against
SGIV-infected cells.
AB - As the major viral pathogen of grouper aquaculture, Singapore grouper iridovirus
(SGIV) has caused great economic losses in China and Southeast Asia. In the
previous study, we have generated highly specific ssDNA aptamers against SGIV
infected grouper spleen cells (GS) by Systematic Evolution of Ligands by
Exponential Enrichment technology (SELEX), in which Q2 had the highest binding
affinity of 16.43 nM. In this study, we would try to identify the specific
sequences in the aptamer Q2 that exhibited the high binding affinity to SGIV
infected cells by truncating the original Q2 into some different specific
segments. We first evaluated the specificity and binding affinity of these
truncated aptamers to SGIV-infected cells by flow cytometry, fluorescent imaging
of cells and aptamer-based enzyme-linked apta-sorbent assay (ELASA). We then
performed cytotoxicity analysis, assessment of the inhibitory effects upon SGIV
infection and the celluar internalization kinetics of each truncated aptamer.
Compared to the initial Q2, one of the truncated aptamer Q2-C5 showed a 3-fold
increase in the binding affinity for SGIV-infected cells, and held more effective
inhibitory effects, higher internalization kinetics and stability. Hence, the
aptamer's truncated methods could be applied in the research of identifying
aptamer's key sequences. The shorter, structure optimizing aptamer showed more
excellent performance over the originally selected aptamer, which could
potentially be applied in developing commercial detection probes for the early
and rapid diagnosis of SGIV infection, and highly specific therapeutic drugs
against SGIV infection.
PMID- 29341877
TI - Characterizing the effects of insertion of a 5.2 kb region of a VACV genome,
which contains known immune evasion genes, on MVA immunogenicity.
AB - Modified Vaccinia virus Ankara (MVA) is an attenuated Vaccinia virus (VACV) that
is a popular vaccine vector candidate against many different pathogens. Its
replication-restricted nature makes it a safe vaccine. However, higher doses or
multiple boosts of MVA are necessary to elicit an immune response similar to wild
type VACV. Multiple strategies have been used to create modified MVA viruses that
remain safe, but have increased immunogenicity. For example, one common strategy
is to delete MVA immunomodulatory proteins in hopes of increasing the host immune
response. Here, we take the opposite approach and examine, for the first time,
how re-introduction of a 5.2 kb region of VACV DNA (that codes for multiple
immunomodulatory proteins) into MVA alters viral immunogenicity. Since antigen
presenting cells (APCs) are critical connectors between the innate and adaptive
immune system, we examined the effect of MVA/5.2 kb infection in these cells in
vitro. MVA/5.2 kb infection decreased virus-induced apoptosis and virus-induced
NF-kappaB activation. MVA.5.2 kb infection decreased TNF production. However,
MVA/5.2 kb infection did not alter APC maturation or IL-6 and IL-8 production in
vitro. We further explored MVA/5.2 kb immunogenicity in vivo. VACV-specific CD8+
T cells were decreased after in vivo infection with MVA/5.2 kb versus MVA,
suggesting that the MVA/5.2 kb construct is less immunogenic than MVA. These
results demonstrate the limitations of in vitro studies for predicting the
effects of genetic manipulation of MVA on immunogenicity. Although MVA/5.2 kb did
not enhance MVA's immunogenicity, this study examined an unexplored strategy for
optimizing MVA, and the insight gained from these results can help direct how to
modify MVA in the future.
PMID- 29341878
TI - Concentrations of arsenic and lead in rice (Oryza sativa L.) in Iran: A
systematic review and carcinogenic risk assessment.
AB - Exposure to heavy metals such as arsenic (As), lead (Pb), and cadmium (Cd) in
either the short or the long term can cause cancers in humans. Dietary intake and
consumption of rice (Oryza sativa L.) is increasing in Iran, and several studies
on the concentration of heavy metals in rice have been carried out in this
country in recent years. In this perspective, the main objective of the present
study was to investigate, even via a meta-analysis of the existing literature,
the presence of As and Pb in rice from many geographical areas in Iran, as well
as to estimate the carcinogenic risk of these heavy metals in rice consumers. The
results of the present ten years-spanning systematic review indicate that 21
reports, collecting a total of 2088 samples, were performed between 2008 and
October 2017. The minimum and maximum concentration of As was observed in the
Golestan area (0.01 +/- 0.01 mg/kg d.w) and the Gillan region (3 mg/kg d.w); and
Pb in the Shahrekord (0.07 +/- 0.02 mg/kg d.w) and Mazandaran (35 mg/kg d.w). The
meta-analysis of data showed that pooled concentration of As in the rice was 0.04
(95%CI: 0.02-0.06 mg/kg d.w), which resulted lower than the National Standard
(NS) limits. However, the pooled concentration of Pb in the rice was 0.38 (95%CI:
0.25-0.5 mg/kg d.w), i.e., higher than NS limits. The heterogeneity was
significant between As (I2 = 63%, P value = .003) and Pb (I2 = 96%, P value <
.001) studies. The carcinogenic risk assessment showed that minimum and maximum
incremental lifetime cancer risk (ILCR) of As was in the 45-54 (4.53 * 10-2) and
15-24 (5.50 * 10-2) year age groups consumers; and Pb, 45-54 (2.442 * 10-3) and
15-24 (2.96 * 10-3), respectively. The overall carcinogenesis risk of As (4.864 *
10-2) was 18.5 times higher than Pb (2.623 * 10-3). All age groups consumers of
rice content of As and Pb are at considerable carcinogenesis risk (ILCR > 10-3).
Therefore a decreased level of heavy metals in rice cultivation should be
encouraged and performed in next planning.
PMID- 29341880
TI - Targetable long non-coding RNAs in cancer treatments.
AB - Aberrant expression of many long non-coding RNAs has been observed in various
types of cancer, implicating their crucial roles in tumorigenesis and cancer
progression. Emerging knowledge with regard to the critical physiological and
pathological roles of long non-coding RNAs in cancers makes them potential
targets in cancer treatments. In this review, we present a summary of the
relatively well studied long non-coding RNAs that are involved in oncogenesis and
outline their functions and functional mechanisms. Recent findings that may be
utilized in therapeutic intervention are also highlighted. With the fast
development in nucleic acid-based therapeutic reagents that can target disease
associated RNAs, lncRNAs should be explored as potential targets in cancer
treatments.
PMID- 29341879
TI - Mechanisms of mitochondrial toxicity of the kinase inhibitors ponatinib,
regorafenib and sorafenib in human hepatic HepG2 cells.
AB - Previous studies have shown that certain kinase inhibitors are mitochondrial
toxicants. In the current investigation, we determined the mechanisms of
mitochondrial impairment by the kinase inhibitors ponatinib, regorafenib, and
sorafenib in more detail. In HepG2 cells cultured in galactose and exposed for 24
h, all three kinase inhibitors investigated depleted the cellular ATP pools at
lower concentrations than cytotoxicity occurred, compatible with mitochondrial
toxicity. The kinase inhibitors impaired the activity of different complexes of
the respiratory chain in HepG2 cells exposed to the toxicants for 24 h and in
isolated mouse liver mitochondria exposed acutely. As a consequence, they
increased mitochondrial production of ROS in HepG2 cells in a time- and
concentration-dependent fashion and decreased the mitochondrial membrane
potential concentration-dependently. In HepG2 cells exposed for 24 h, they
induced mitochondrial fragmentation, lysosome content and mitophagy as well as
mitochondrial release of cytochrome c, leading to apoptosis and/or necrosis. In
conclusion, the kinase inhibitors ponatinib, regorafenib, and sorafenib impaired
the function of the respiratory chain, which was associated with increased ROS
production and a drop in the mitochondrial membrane potential. Despite activation
of defense measures such as mitochondrial fission and mitophagy, some cells were
liquidated concentration-dependently by apoptosis or necrosis. Mitochondrial
dysfunction may represent a toxicological mechanism of hepatotoxicity associated
with certain kinase inhibitors.
PMID- 29341881
TI - Clinical Implications of Technological Advances in Screening for Atrial
Fibrillation.
AB - The incidence of atrial fibrillation (AF) continues to increase worldwide as
people live longer. AF is the leading cause of stroke among patients older than
75 years and is responsible for at least 15% of all strokes. Industry has
responded to this problem with a plethora of monitoring devices. These include
single lead ECG adhesive sensors, implantable loop recorders, smartphone
attachments and wearables. This review will concentrate on clinical studies using
these technologies. There are wearables including watches and watch-like devices
that will be mentioned but these have not been validated for clinical use. This
review will begin with a background regarding screening for AF and at the end
present findings from Cardiac Implantable devices that could influence use of the
new mobile health technologies.
PMID- 29341882
TI - Development and evaluation of a website for surveillance of healthcare-associated
urinary tract infections in Australia.
AB - Phase II of the Surveillance to Reduce Urinary Tract Infections project piloted a
website for point prevalence surveys of healthcare-associated (HAUTI) and
catheter-associated urinary tract infection in Australian hospitals and aged care
homes. This report describes development and evaluation of the website for online
data collection. Evaluation findings from 38 data collectors indicated that most
respondents found website registration and web form use easy (N = 22; 58% and N =
16; 43%, respectively). The need for improved computer literacy skills and
automated data systems were highlighted. This study demonstrated a novel approach
for Australian HAUTI data collection; however, refinements are needed before
national roll-out.
PMID- 29341883
TI - Brain-region-specific Molecular Responses to Maternal Separation and Social
Defeat Stress in Mice.
AB - The association between stress and mental illness has been well documented, but
the molecular consequences of repeated exposure to stress have not been
completely identified. The present study sought to elucidate the combinatorial
effects of early-life maternal separation stress and adult social defeat stress
on alterations in signal transduction and gene expression that have been
previously implicated in susceptibility to psychosocial stress. Molecular
analyses were performed in the prelimbic/infralimbic cortex, amygdala, and
nucleus accumbens, three brain regions that have been suggested to play critical
roles in determining stress responses. The current data reveal that both maternal
separation and social defeat significantly impact the expression of genes
involved in histone methylation and the beta-catenin-, endogenous opioid-,
neurotrophin-, and glucocorticoid signaling pathways. Although the effects of
maternal separation and social defeat were largely non-overlapping, a subset of
genes in each brain region were governed by additive, opposing, or other types of
interactions between these stress paradigms, thus highlighting potential
molecular mechanisms through which these stressors might coordinately regulate
brain function and behavior.
PMID- 29341884
TI - Acute Stress Persistently Alters Locus Coeruleus Function and Anxiety-like
Behavior in Adolescent Rats.
AB - Stress is a physiological state characterized by altered neuroendocrine
signaling, behavioral arousal, and anxiety. Chronic or traumatic stress may
predispose individuals for multiple somatic and psychiatric illnesses. The locus
coeruleus (LC) is a major node in the stress response that integrates input from
multiple stress responsive neural circuits and releases norepinephrine (NE)
throughout the central nervous system (CNS) to promote vigilance and anxiety.
Many mood disorders associated with prior stress are characterized by chronically
altered noradrenergic signaling, yet the long-term impact of an acute stressor on
LC function is not clear. To determine how acute stress could affect anxiety-like
behavior as well as LC function at immediate and extended time points, rats
underwent simultaneous exposure to physical restraint and predator odor. Rats
underwent behavioral testing immediately or one week after stressor exposure and
were then sacrificed for whole-cell patch-clamp recordings of LC neurons. Stress
caused an immediate increase in anxiety-like behaviors in the elevated plus maze
(EPM), as well decreased excitatory synaptic transmission and increased
spontaneous discharge in LC neurons. These effects persisted for seven days after
stress. Importantly, the excitability of LC neurons was increased one week post
stress, but not immediately after, suggesting a long-term adaptation by the
system. Rats tested in the open field one week after stress also showed increased
anxiety-like behaviors. These findings show that a single acute stressor is
capable of precipitating long-lasting changes in the LC function that may be
related to some of the behavioral effects of stress, potentially contributing to
stress-induced disease pathogenesis.
PMID- 29341885
TI - Deletion of the Duffy antigen receptor for chemokines (DARC) promotes insulin
resistance and adipose tissue inflammation during high fat feeding.
AB - OBJECTIVE: Inflammation in adipose tissues in obesity promotes insulin resistance
and metabolic disease. The Duffy antigen receptor for chemokines (DARC) is a
promiscuous non-signaling receptor expressed on erythrocytes and other cell types
that modulates tissue inflammation by binding chemokines such as monocyte
chemoattractant protein-1 (MCP-1) and by acting as a chemokine reservoir. DARC
allelic variants are common in humans, but the role of DARC in modulating obesity
related metabolic disease is unknown. METHODS: We examined body weight gain,
tissue adiposity, metabolic parameters and inflammatory marker expression in wild
type and DARC knockout mice fed a chow diet (CD) and high fat diet (HFD).
RESULTS: Compared to wild-type mice, HFD-fed DARC knockout mice developed glucose
intolerance and insulin resistance independent of increases in body weight or
adiposity. Interestingly, insulin sensitivity was also diminished in lean male
DARC knockout mice fed a chow diet. Insulin production was not reduced by DARC
gene deletion, and plasma leptin levels were similar in HFD fed wild-type and
DARC knockout mice. MCP-1 levels in plasma rose significantly in the HFD fed wild
type mice, but not in the DARC knockout mice. Conversely, adipose tissue MCP-1
levels were higher, and more macrophage crown-like structures were detected, in
the HFD fed DARC knockout mice as compared with the wild-type mice, consistent
with augmented adipose tissue inflammation that is not accurately reflected by
plasma levels of DARC-bound MCP-1 in these mice. CONCLUSIONS: These findings
suggest that DARC regulates metabolic function and adipose tissue inflammation,
which may impact obesity-related disease in ethnic populations with high
frequencies of DARC allelic variants.
PMID- 29341886
TI - Regulation of HSF1 protein stabilization: An updated review.
AB - Heat shock factor 1 (HSF1) is a transcriptional factor that determines the
efficiency of heat shock responses (HSRs) in the cell. Given its function has
been extensively studied in recent years, HSF1 is considered a potential target
for the treatment of disorders associated with protein aggregation. The activity
of HSF1 is traditionally regulated at the transcriptional level in which the
transactivation domain of HSF1 is modified by extensive array of pos
translational modifications, such as phosphorylation, sumoylation, and
acetylation. Recently, HSF1 is also reported to be regulated at the monomeric
level. For example, in neurodegenerative disorders such as Huntington's disease
and Alzheimer's disease the expression levels of the monomeric HSF1 are found to
be reduced markedly. Methylene blue (MB) and riluzole, two clinical available
drugs, increase the amount of the monomeric HSF1 in both cells and animals. Since
the monomeric HSF1 not only determines the efficiency of HSRs, but exerts
protective effects in a trimerization-independent manner, increasing the amount
of the monomeric HSF1 via stabilization of HSF1 may be an alternative strategy
for the amplification of HSR. However, to date we have no outlined knowledges
about HSF1 protein stabilization, though studies regarding the regulation of the
monomeric HSF1 have been documented in recent years. Here, we summarize the
regulation of the monomeric HSF1 by some previously reported factors, such as
synuclein, Huntingtin (Htt), TDP-43, unfolded protein response (UPR), MB and
doxorubicin (DOX), as well as their possible mechanisms, aiming to push the
understanding about HSF1 protein stabilization.
PMID- 29341887
TI - Molecular Basis of Substrate Polyspecificity of the Candida albicans Mdr1p
Multidrug/H+ Antiporter.
AB - The molecular basis of polyspecificity of Mdr1p, a major drug/H+ antiporter of
Candida albicans, is not elucidated. We have probed the nature of the drug
binding pocket by performing systematic mutagenesis of the 12 transmembrane
segments. Replacement of the 252 amino acid residues with alanine or glycine
yielded 2/3 neutral mutations while 1/3 led to the complete or selective loss of
resistance to drugs or substrates transported by the pump. Using the GlpT-based
3D-model of Mdr1p, we roughly categorized these critical residues depending on
their type and localization, 1 degrees / main structural impact ("S" group), 2
degrees / exposure to the lipid interface ("L" group), 3 degrees / buried but not
facing the main central pocket, inferred as critical for the overall H+/drug
antiport mechanism ("M" group) and finally 4 degrees / buried and facing the main
central pocket ("B" group). Among "B" category, 13 residues were essential for
the large majority of drugs/substrates, while 5 residues were much substrate
specific, suggesting a role in governing polyspecificity (P group). 3D
superposition of the substrate-specific MFS Glut1 and XylE with the MDR substrate
polyspecific MdfA and Mdr1p revealed that the B group forms a common substrate
interaction core while the P group is only found in the 2 MDR MFS transporters,
distributed into 3 areas around the B core. This specific pattern has let us to
propose that the structural basis for polyspecificity of MDR MFS transporters is
the extended capacity brought by residues located at the periphery of a binding
core to accomodate compounds differing in size and type.
PMID- 29341888
TI - Protection against the Neurotoxic Effects of beta-Amyloid Peptide on Cultured
Neuronal Cells by Lovastatin Involves Elevated Expression of alpha7 Nicotinic
Acetylcholine Receptors and Activating Phosphorylation of Protein Kinases.
AB - The treatment of neurodegenerative diseases with statins has drawn increasing
attention, but the related molecular mechanisms remain elusive. To examine the
pleiotropic cholesterol-independent effects of statins in connection with the
treatment of Alzheimer disease, we probed the influence of lovastatin on the
metabolism of amyloid precursor protein (APP), expression of nicotinic
acetylcholine receptors (nAChRs), and activity of mitogen-activated protein
kinase (MAPK) in primary cultured neurons and SH-SY5Y cells overexpressing human
APP670/671. Lovastatin attenuated the neurotoxic effects of beta-amyloid peptide
(Abeta) and affected the metabolism of APP, reducing levels of Abeta1 to Abeta42
and beta-site amyloid precursor protein-cleaving enzyme 1; enhancing those of
alphaAPP, disintegrin metalloproteinase domain-containing protein 10, and beta
site amyloid precursor protein-cleaving enzyme 2; and up-regulating expression of
alpha7 nAChR and stimulating phosphorylation of extracellular signal-regulated
kinase (ERK)1/2. Interestingly, methyllycaconitine, an antagonist of alpha7
nAChR, attenuated this effect on alphaAPP, but not on phospho-ERK1/2; whereas
U0126, an inhibitor of MAPK/ERK kinase/ERK, blocked both the elevated expression
of alpha7 nAChR and enhanced secretion of alphaAPP. Our findings indicate that
lovastatin up-regulates expression of alpha7 nAChR by a mechanism involving
activation of the MAPK/ERK pathway, which may result in diminished production of
Abeta.
PMID- 29341889
TI - Adventitial Activation in the Pathogenesis of Injury-Induced Arterial Remodeling:
Potential Implications in Transplant Vasculopathy.
AB - Transplant vasculopathy is one of the major causes of chronic rejection after
solid organ transplantation. The pathogenic mechanisms of transplant vasculopathy
are still poorly understood. Herein, we summarize current evidence suggesting
that activation of the tunica adventitia may be involved in the pathogenesis of
transplant vasculopathy. Adventitia is an early responder to various vascular
injuries and plays an integral role in eliciting vascular inflammation and
remodeling. Accumulation of macrophages in the adventitia promotes the
development of vascular remodeling by releasing a variety of paracrine factors
that have profound impacts on vascular mural cells. Targeting adventitial
macrophages has been shown to be effective for repressing transplantation-induced
arterial remodeling in animal models. Adventitia also fosters angiogenesis, and
neovascularization of the adventitial layer may facilitate the transport of
inflammatory cells through the arterial wall. Further investigations are
warranted to clarify whether inhibiting adventitial oxidative stress and/or
adventitial neovascularization are better strategies for preventing transplant
vasculopathy.
PMID- 29341890
TI - Periodontal diseases and adverse pregnancy outcomes: Is there a role for vitamin
D?
AB - Studies have shown a relationship between maternal periodontal diseases (PDs) and
premature delivery. PDs are commonly encountered oral diseases which cause
progressive damage to the periodontal ligament and alveolar bones, leading to
loss of teeth and oral disabilities. PDs also adversely affect general health by
worsening of cardiovascular and metabolic diseases. Moreover, maternal PDs are
thought to be related to increasing the frequency of preterm-birth with low birth
weight (PBLBW) in new-borns. Prematurity and immaturity are the leading causes of
prenatal and infant mortality and is a major public health problem around the
world. Inflamed periodontal tissues generate significantly high levels of
proinflammatory cytokines that may have systemic effects on the host mother and
the fetus. In addition, the bacteria that cause PDs produce endotoxins which can
harm the fetus. Furthermore, studies have shown that microorganisms causing PDs
can get access to the bloodstream, invading uterine tissues, to induce PBLBW.
Another likely mechanism that connects PDs with adverse pregnancy outcome is
maternal vitamin D status. A role of inadequate vitamin D status in the genesis
of PDs has been reported. Administration of vitamin D supplementation during
pregnancy could reduce the risk of maternal infections and adverse pregnancy
outcomes. As maternal PDs are significant risk factors for adverse pregnancy
outcome, preventive antenatal care for pregnant women in collaboration with the
obstetric and dental professions are required.
PMID- 29341891
TI - Long-term treadmill exercise improves memory impairment through restoration of
decreased synaptic adhesion molecule 1/2/3 induced by transient cerebral ischemia
in the aged gerbil hippocampus.
AB - Exercise improves cognitive impairments induced by transient cerebral ischemia,
and modulates synaptic adhesion molecules. In this study, we investigated effects
of long-term treadmill exercise on cognitive impairments and its relation to
changes of synaptic cell adhesion molecule (SynCAM) 1/2/3 in the hippocampus
after 5 min of transient cerebral ischemia in aged gerbils. Animals were assigned
to sedentary and exercised groups, given treadmill exercise for 4 consecutive
weeks from 5 days after transient ischemia, and evaluated cognitive function
through passive avoidance test and Morris water maze test. SynCAM 2 protein
levels were determined in the hippocampus by western blot. In addition, neuronal
and synaptic changes were examined by NeuN immunohistochemistry, and SynCAM 1/2/3
and MAP2 double immunofluorescence, respectively. We found that transient
cerebral ischemia led to neuronal death in the CA1 area and dentate gyrus, and
impaired -memory function; however, 4 weeks of treadmill exercise improved
ischemia-induced memory impairment. In addition, SynCAM 1/2/3 and SynCAM 2
expression in the hippocampus was significantly decreased in the sedentary group
after transient cerebral ischemia; however, SynCAM 1/2/3 expressionand and SynCAM
2 protein level was significantly increased in the ischemic group with exercise.
These results suggest that long-term treadmill exercise improves memory
impairment through the restoration of decreased SynCAM 1/2/3 expression in the
hippocampus induced by transient cerebral ischemia in the aged gerbil.
PMID- 29341892
TI - Premature aging in behavior and immune functions in tyrosine hydroxylase
haploinsufficient female mice. A longitudinal study.
AB - Aging is accompanied by impairment in the nervous, immune, and endocrine systems
as well as in neuroimmunoendocrine communication. In this context, there is an
age-related alteration of the physiological response to acute stress, which is
modulated by catecholamine (CA), final products of the sympathetic-adreno
medullary axis. The involvement of CA in essential functions of the nervous
system is consistent with the neuropsychological deficits found in mice with
haploinsufficiency (hemizygous; HZ) of tyrosine hydroxylase (TH) enzyme (TH-HZ).
However, other possible alterations in regulatory systems have not been studied
in these animals. The aim of the present work was to analyze whether adult TH-HZ
female mice presented the impairment of behavioral traits and immunological
responses that occurs with aging and whether they had affected their mean
lifespan. ICR-CD1 female TH-HZ and wild type (WT) mice were used in a
longitudinal study. Behavioral tests were performed on adult and old mice in
order to evaluate their sensorimotor abilities and exploratory capacity, as well
as anxiety-like behaviors. At the ages of 2 +/- 1, 4 +/- 1, 9 +/- 1, 13 +/- 1 and
20 +/- 1 months, peritoneal leukocytes were extracted and several immune
functions were assessed (phagocytic capacity, Natural Killer (NK) cytotoxicity,
and lymphoproliferative response to lipopolysaccharide (LPS) and concanavalin A
(ConA)). In addition, several oxidative stress parameters (catalase, glutathione
reductase and glutathione peroxidase activities, and reduced glutathione (GSH)
concentrations as antioxidant compounds as well as xanthine oxidase activity,
oxidized glutathione (GSSG) concentrations, and GSSG/GSH ratio as oxidants) were
analyzed. As inflammatory stress parameters TNF-alpha and IL-10 concentrations,
and TNF-alpha/IL-10 ratios as inflammatory/anti-inflammatory markers, were
measured. Animals were maintained in standard conditions until their natural
death. The results indicate that adult TH-HZ mice presented worse sensorimotor
abilities and exploratory capacity than their WT littermates as well as greater
anxiety-like behaviors. With regards to the immune system, adult TH-HZ animals
exhibited lower values of phagocytic capacity, NK cytotoxicity, and
lymphoproliferative response to LPS and ConA than WT mice. Moreover, immune cells
of TH-HZ mice showed higher oxidative and inflammatory stress than those of WT
animals. Although these differences between TH-HZ and WT, in general, decreased
with aging, this premature immunosenescence and impairment of behavior of TH-HZ
mice was accompanied by a shorter mean lifespan in comparison to WT counterparts.
In conclusion, haploinsufficiency of th gene in female mice appears to provoke
premature aging of the regulatory systems affecting mean lifespan.
PMID- 29341893
TI - Targeting BDNF modulation by plant glycosides as a novel therapeutic strategy in
the treatment of depression.
AB - Current therapies in clinical practice face strong criticism regarding their
efficacy, and side effects, which forced the neuro-researchers to discover novel
agents with different mechanistic insights. Glycosides are naturally-occurring
plant secondary metabolites with significant medicinal potential and clinical
scope as antidepressant. The aim of this review is to focus on the antidepressant
effects of glycosides in preclinical studies, with an emphasis on the possible
mechanisms. The literature search revealed that only a few phytoglycosides have
been evaluated for their relevance in depression alleviation. Through preclinical
tests, it has come forth that the efficacy is mediated by the modulation of brain
derived neurotrophic factor (BDFN) in the hippocampus, that is known for
promoting synaptic efficacy, neuronal connectivity and neuroplasticity. Thus,
attempting the upregulation of BDNF expression by plant glycosides can be a novel
therapeutic strategy for the treatment of depression. The outcome of this review
can stimulate neuroscientists to evaluate plant-derived glycosides for the
treatment of depression, as these structurally-complex and diverse molecules,
might usher in a new paradigm in the treatment of depression, with a better
efficacy and tolerability.
PMID- 29341894
TI - Protective effects of antioxidin-RL from Odorrana livida against ultraviolet B
irradiated skin photoaging.
AB - The unavoidable daily exposure of the skin to ultraviolet (UV) B radiation is
proven to have deleterious effects. The action mechanism of antioxidin-RL, an
antioxidant peptide purified from skin secretions of frog Odorrana livida with
amino acid sequence of AMRLTYNRPCIYAT, is well characterized by NMR titration and
mutation based on ABTS+ scavenging activities. In order to explore the protective
effects of antioxidin-RL against UVB-irradiated skin photoaging, cell uptake
assay was used to detect the location of antioxidin-RL molecules serving various
biological functions in the cells. The protective effects of antioxidin-RL on UVB
induced response were examined in vitro and in vivo. Results showed that
antioxidin-RL successfully penetrated the cell membrane and exerted a positive
effect on cell migration. It also effectively inhibited the UVB-induced excessive
production of ROS and prevented oxidative damage to DNAs and proteins. Moreover,
the mRNA expressions of MMP-1, VEGF, COX-2, and pro-inflammatory cytokines, such
as IL-6 and TNF-alpha in antioxidin-RL-treated HaCaT and HSF cells were
significantly down-regulated whereas those of FGF, procollagen type I and TGF
beta1 up-regulated. Antioxidin-RL effectively prevented UVB-induced erythema on
mouse skin, thereby inhibiting UVB-induced skin thickening and inflammation and
increasing collagen deposition as demonstrated by in vivo experiments. Hence, the
novel antioxidant peptide antioxidin-RL can effectively reduce UVB-induced skin
reactions in vivo and in vitro, providing potential molecules against UVB-induced
inflammation and photoaging.
PMID- 29341895
TI - Prenatal paracetamol exposure and child neurodevelopment: A review.
AB - BACKGROUND: The non-prescription medication paracetamol (acetaminophen, APAP) is
currently recommended as a safe pain and fever treatment during pregnancy.
However, recent studies suggest a possible association between APAP use in
pregnancy and offspring neurodevelopment. OBJECTIVES: To conduct a review of
publications reporting associations between prenatal APAP use and offspring
neurodevelopmental outcomes. METHODS: Relevant sources were identified through a
key word search of multiple databases (Medline, CINAHL, OVID and TOXNET) in
September 2016. All English language observational studies of pregnancy APAP and
three classes of neurodevelopmental outcomes (autism spectrum disorder (ASD),
attention deficit hyperactivity disorder (ADHD), and intelligence quotient (IQ))
were included. One reviewer (AZB) independently screened all titles and
abstracts, extracted and analyzed the data. RESULTS: 64 studies were retrieved
and 55 were ineligible. Nine prospective cohort studies fulfilled all inclusion
criteria. Data pooling was not appropriate due to heterogeneity in outcomes. All
included studies suggested an association between prenatal APAP exposure and the
neurodevelopmental outcomes; ADHD, ASD, or lower IQ. Longer duration of APAP use
was associated with increased risk. Associations were strongest for hyperactivity
and attention-related outcomes. Little modification of associations by indication
for use was reported. CONCLUSIONS: Together, these nine studies suggest an
increased risk of adverse neurodevelopmental outcomes following prenatal APAP
exposure. Further studies are urgently needed with; precise indication of use and
exposure assessment of use both in utero and in early life. Given the current
findings, pregnant women should be cautioned against indiscriminate use of APAP.
These results have substantial public health implications.
PMID- 29341896
TI - Luteinizing hormone signaling phosphorylates and activates the cyclic GMP
phosphodiesterase PDE5 in mouse ovarian follicles, contributing an additional
component to the hormonally induced decrease in cyclic GMP that reinitiates
meiosis.
AB - Prior to birth, oocytes within mammalian ovarian follicles initiate meiosis, but
then arrest in prophase until puberty, when with each reproductive cycle, one or
more follicles are stimulated by luteinizing hormone (LH) to resume meiosis in
preparation for fertilization. Within preovulatory follicles, granulosa cells
produce high levels of cGMP, which diffuses into the oocyte to maintain meiotic
arrest. LH signaling restarts meiosis by rapidly lowering the levels of cGMP in
the follicle and oocyte. Part of this decrease is mediated by the
dephosphorylation and inactivation the NPR2 guanylyl cyclase in response to LH,
but the mechanism for the remainder of the cGMP decrease is unknown. At least one
cGMP phosphodiesterase, PDE5, is activated by LH signaling, which would
contribute to lowering cGMP. PDE5 exhibits increased cGMP-hydrolytic activity
when phosphorylated on serine 92, and we recently demonstrated that LH signaling
phosphorylates PDE5 on this serine and increases its activity in rat follicles.
To test the extent to which this mechanism contributes to the cGMP decrease that
restarts meiosis, we generated a mouse line in which serine 92 was mutated to
alanine (Pde5-S92A), such that it cannot be phosphorylated. Here we show that
PDE5 phosphorylation is required for the LH-induced increase in cGMP-hydrolytic
activity, but that this increase has only a modest effect on the LH-induced cGMP
decrease in mouse follicles, and does not affect the timing of meiotic
resumption. Though we show that the activation of PDE5 is among the mechanisms
contributing to the cGMP decrease, these results suggest that another cGMP
phosphodiesterase is also activated by LH signaling.
PMID- 29341897
TI - Toxicity and toxicokinetics of Amanita exitialis in beagle dogs.
AB - In this study, the toxicology of A. exitialis, a lethal mushroom found in China,
and the toxicokinetics of peptide toxins contained in it were evaluated. Beagles
were fed A. exitialis powder (20 or 60 mg/kg) in starch capsules, after which
they were assessed for signs of toxicity, as well as biochemical and pathological
changes. Ultra-performance liquid chromatography-electrospray ionization-tandem
mass spectrometry was used to assay the peptide toxins. The total peptide toxins
in A. exitialis was 3482.6 +/- 124.94 mg/kg. The beagles showed signs of
toxicity, such as vomiting and diarrhea, at 12-48 h following ingestion of A.
exitialis. Furthermore, alanine transaminase and aspartate transaminase levels in
plasma, as well as prothrombin time and activated partial thromboplastin time
peaked at 36 h post A. exitialis ingestion. Furthermore, total bilirubin and
alkaline phosphatase levels peaked at 48 h after A. exitialis ingestion. Three
dogs that were administered 60 mg/kg A. exitialis died at 24-72 h after ingesting
the capsules. Additionally, liver histopathological examinations showed
hemorrhagic necrosis of hepatocytes. alpha-Amanitin, beta-amanitin, and
phallacidin were rapidly absorbed and eliminated from plasma after A. exitialis
was ingested. A long latency period (12-24 h post A. exitialis ingestion) was
observed in the dogs before the onset of gastrointestinal symptoms. There was
acute liver damage thereafter. Gastric lavage and enhanced plasma clearance
methods such as hemodialysis, hemoperfusion, or plasma exchange may be
ineffective in removing amatoxins from blood at 12 h post A. exitialis ingestion.
Enhanced excretion of amatoxins in urine could be effective within 2 days after
ingestion of A. exitialis because amatoxins in 0-2 d urine accounted for more
than 90% of the total urine excretion.
PMID- 29341899
TI - Accurate prediction of vaccine stability under real storage conditions and during
temperature excursions.
AB - Due to their thermosensitivity, most vaccines must be kept refrigerated from
production to use. To successfully carry out global immunization programs,
ensuring the stability of vaccines is crucial. In this context, two important
issues are critical, namely: (i) predicting vaccine stability and (ii) preventing
product damage due to excessive temperature excursions outside of the recommended
storage conditions (cold chain break). We applied a combination of advanced
kinetics and statistical analyses on vaccine forced degradation data to
accurately describe the loss of antigenicity for a multivalent freeze-dried
inactivated virus vaccine containing three variants. The screening of large
amounts of kinetic models combined with a statistical model selection approach
resulted in the identification of two-step kinetic models. Predictions based on
kinetic analysis and experimental stability data were in agreement, with
approximately five percentage points difference from real values for long-term
stability storage conditions, after excursions of temperature and during
experimental shipments of freeze-dried products. Results showed that modeling a
few months of forced degradation can be used to predict various time and
temperature profiles endured by vaccines, i.e. long-term stability, short time
excursions outside the labeled storage conditions or shipments at ambient
temperature, with high accuracy. Pharmaceutical applications of the presented
kinetics-based approach are discussed.
PMID- 29341898
TI - Induction of alpha-synuclein pathology in the enteric nervous system of the rat
and non-human primate results in gastrointestinal dysmotility and transient CNS
pathology.
AB - Alpha-Synuclein (alpha-syn) is by far the most highly vetted pathogenic and
therapeutic target in Parkinson's disease. Aggregated alpha-syn is present in
sporadic Parkinson's disease, both in the central nervous system (CNS) and
peripheral nervous system (PNS). The enteric division of the PNS is of particular
interest because 1) gastric dysfunction is a key clinical manifestation of
Parkinson's disease, and 2) Lewy pathology in myenteric and submucosal neurons of
the enteric nervous system (ENS) has been referred to as stage zero in the Braak
pathological staging of Parkinson's disease. The presence of Lewy pathology in
the ENS and the fact that patients often experience enteric dysfunction before
the onset of motor symptoms has led to the hypothesis that alpha-syn pathology
starts in the periphery, after which it spreads to the CNS via interconnected
neural pathways. Here we sought to directly test this hypothesis in rodents and
non-human primates (NHP) using two distinct models of alpha-syn pathology: the
alpha-syn viral overexpression model and the preformed fibril (PFF) model.
Subjects (rat and NHP) received targeted enteric injections of PFFs or adeno
associated virus overexpressing the Parkinson's disease associated A53T alpha-syn
mutant. Rats were evaluated for colonic motility monthly and sacrificed at 1, 6,
or 12 months, whereas NHPs were sacrificed 12 months following inoculation, after
which the time course and spread of pathology was examined in all animals. Rats
exhibited a transient GI phenotype that resolved after four months. Minor alpha
syn pathology was observed in the brainstem (dorsal motor nucleus of the vagus
and locus coeruleus) 1 month after PFF injections; however, no pathology was
observed at later time points (nor in saline or monomer treated animals).
Similarly, a histopathological analysis of the NHP brains revealed no pathology
despite the presence of robust alpha-syn pathology throughout the ENS which
persisted for the entirety of the study (12 months). Our study shows that
induction of alpha-syn pathology in the ENS is sufficient to induce GI
dysfunction. Moreover, our data suggest that sustained spread of alpha-syn
pathology from the periphery to the CNS and subsequent propagation is a rare
event, and that the presence of enteric alpha-syn pathology and dysfunction may
represent an epiphenomenon.
PMID- 29341901
TI - A small peptide derived from BMP-9 can increase the effect of bFGF and NGF on SH
SY5Y cells differentiation.
AB - The current aging of the world population will increase the number of people
suffering from brain degenerative diseases such as Alzheimer's disease (AD).
There are evidence showing that the use of growth factors such as BMP-9 could
restored cognitive function as it acts on many AD hallmarks at the same time.
However, BMP-9 is a big protein expensive to produce that can hardly access the
central nervous system. We have therefore developed a small peptide, SpBMP-9,
derived from the knuckle epitope of BMP-9 and showed its therapeutic potential in
a previous study. Since it is known that the native protein, BMP-9, can act in
synergy with other growth factors in the context of AD, here we study the
potential synergistic effect of various combinations of SpBMP-9 with bFGF, EGF,
IGF-2 or NGF on the cholinergic differentiation of human neuroblastoma cells SH
SY5Y. We found that, in opposition to IGF-2 or EGF, the combination of SpBMP-9
with bFGF or NGF can stimulate to a greater extent the neurite outgrowth and
neuronal differentiation toward the cholinergic phenotype as shown by expression
and localization of the neuronal markers NSE and VAchT and the staining of
intracellular calcium. Those results strongly suggest that SpBMP-9 plus NGF or
bFGF are promising therapeutic combinations against AD that required further
attention.
PMID- 29341900
TI - Lamotrigine loaded poly-E-(d,l-lactide-co-caprolactone) nanoparticles as brain
delivery system.
AB - Management of epilepsy requires brain delivery therapy, therefore, this study was
aimed to prepare lamotrigine loaded poly-E-(d,l-lactide-co-caprolactone) (PLCL)
nanoparticles using spontaneous emulsification solvent diffusion method.
Nanoparticles for brain delivery required to have a particle size <200 nm,
polydispesity index <0.2 and a sustained drug release properties. For such aim
different factors were considered in preparing the nanoparticles as PLCL
monomers' ratio, type of organic solvent used to prepare the nanoparticles,
amount of PLCL and Pluronic(r)F127 in the nanoparticles. Prepared nanoparticles
were characterized for their shape, particle size, polydispersity index, zeta
potential, encapsulation efficiency, drug loading capacity, process yield and in
vitro drug release pattern. The in-vivo investigation for brain delivery of
selected nanoparticles delivered by intravenous route was investigated in rats
and compared to that for oral tablet. The obtained nanoparticles were spherical
in shape. The amount of surfactant and PLCL affected the properties of the
obtained nanoparticles. Using a mixture of organic solvent in preparing the
nanoparticles improved its properties. The nanoparticles prepared using PLCL with
monomers' ratio of 25:75, had particle size value of 125 nm, polydispersity index
value of 0.184, zeta potential value of -39 mV and encapsulation efficiency value
of 99%, was selected to study their efficacy to deliver the drug to the brain.
The tested nanoparticles showed higher values of Tmax, Cmax, AUC, and MRT in
homogenized rat brain, compared to oral lamotrigine tablet, while the
bioavailability of the oral tablet was higher in rat plasma compared to that for
the nanoparticles. This reflects that brain was the main distribution site for
tested nanoparticles, and plasma was the main distribution site for oral tablets.
This confirms the goal of the selected formulation as brain delivery
nanoparticles.
PMID- 29341902
TI - Curcumin potentiates the function of human alpha7-nicotinic acetylcholine
receptors expressed in SH-EP1 cells.
AB - Effects of curcumin, a biologically active ingredient of turmeric, were tested on
the Ca2+ transients induced by the activation of alpha7 subunit of the human
nicotinic acetylcholine (alpha7 nACh) receptor expressed in SH-EP1 cells.
Curcumin caused a significant potentiation of choline (1 mM)-induced Ca2+
transients with an EC50 value of 133 nM. The potentiating effect of curcumin was
not observed in Ca2+ transients induced by high K+ (60 mM) containing solutions
or activation of alpha4beta2 nACh receptors and the extent of curcumin
potentiation was not altered in the presence of Ca2+ channel antagonists
nifedipine (1 MUM), verapamil (1 MUM), omega-conotoxin (1 MUM), and bepridil (10
MUM). Noticeably the effect of curcumin was not observed when curcumin and
choline were co-applied without curcumin pre-incubation. The effect of curcumin
on choline-induced Ca2+ transients was not reversed by pre-incubation with
inhibitors of protein C, A, and CaM kinases. Metabolites of curcumin such as
tetrahydrocurcumin, demethylcurcumin, and didemethylcurcumin also caused
potentiation of choline-induced Ca2+ transients. Notably, specific binding of
[125I]-bungarotoxin was not altered in the presence of curcumin. Collectively,
our results indicate that curcumin allosterically potentiate the function of the
alpha7-nACh receptor expressed in SH-EP1 cells.
PMID- 29341903
TI - Emerging roles and mechanisms of FOXC2 in cancer.
AB - Forkhead box protein C2 (FOXC2), a transcription factor of the forkhead/winged
helix family, is required for embryonic and prenatal development. FOXC2 acts as a
crucial modulator during both angiogenesis and lymphangiogenesis via multiple
angiogenic and lymphangiogenic pathways, respectively. Although recent studies
have shed light on the emerging role of FOXC2 in cancer, very little is known
about the precise underlying mechanisms. The purpose of this review is to
summarize the current understanding of FOXC2 and provide potential mechanistic
explanations of the relationship between FOXC2 and cancer, as well as discuss the
prospect for future research in the promising prognostic value of FOXC2 in
cancer.
PMID- 29341904
TI - A rapid and simple LC-MS/MS method for personalized busulfan dosing in pediatric
patients undergoing hematopoietic stem cell transplantation (HSCT).
AB - BACKGROUND: Busulfan is commonly used as a conditioning regimen before
hematopoietic stem cell transplantation (HSCT). There is a big inter-individual
variability in busulfan exposure and the narrow therapeutic index, especially in
pediatric population. Therefore, to achieve therapeutic efficacy and safety
concurrently, personalized busulfan dosing, guided by pharmacokinetic study with
serial plasma samples, is needed a few hours afterwards. METHODS: A fast,
sensitive, and accurate method for busulfan measurement was developed, validated,
and implemented with liquid-chromatography-mass spectrometry (HPLC-MS/MS). The
sample preparation procedure involves only protein precipitation and dilution,
and the HPLC-MS/MS method takes 3 min/sample. The assay was linear from 10 ng/ml
to 7500 ng/ml (R2 = 0.99). Recoveries were above 90%. The precision was
determined at 3 levels (30, 300 and 4000 ng/ml): the intra-day variability (%CV)
ranged from 1.4% to 2.5% (n = 20); the inter-day variability ranged from 2.2% to
5.5% (n = 20). The accuracy of the HPLC-MS/MS test was evaluated with an old HPLC
fluorescence method (n = 84), and a Correlation Coefficient (R) of 0.99 was
observed. CONCLUSIONS: The analytical performance of the assay allows for timely
dose adjustment and has been implemented in clinical service for better clinical
outcome.
PMID- 29341906
TI - Lateralization of mother-infant interactions in wild horses.
AB - The manifestation of behavioural lateralization has been shown to be modified by
environmental conditions, life experiences, and selective breeding. This study
tests whether the lateralization recently found in feral domestic horse (Equus
caballus) is evident in undomesticated horses. Mother-offspring interactions were
investigated in Przewalski's horse (E. ferus przewalskii) living in their natural
habitat in Mongolia. Lateral position preferences during mare-foal spontaneous
reunions were used as a behavioural marker of visual lateralization. Preferences
were separately assessed for foals' approaches to their mothers and mares'
approaches to their foals. Preference to keep the mother in the visual field of
the left eye was found in various types of foals' behaviour. In slow travelling,
Przewalski's foals showed stronger preference for the left eye use than feral
horse foals. Population-level left-eye bias was also found in mothers approaching
their foals. Our results indicate right-hemispheric dominance for control of
mother-offspring interactions in Przewalski's horses, similar to what has been
reported for other mammals including humans. Benefits conferred by the
lateralized social processing of and responding to social stimuli may explain
that the left-lateralized social behaviour is a robust trait of equine behaviour,
not modified by domestication or specific environmental conditions of the
population.
PMID- 29341905
TI - Intensity difference limens in adult CBA/CaJ mice (Mus musculus).
AB - Mice have emerged as important models of auditory perception and acoustic
communication. To study and model complex sound perception and communication,
basic hearing abilities have to be established, yet intensity difference limens
have not been measured in CBA/CaJ mice. Nine mice were trained using operant
conditioning procedures with positive reinforcement to discriminate sound
intensity across frequencies. Intensity difference limens were measured for 12,
16, 24, and 42 kHz tones at 10 and 30 dB sensation levels. Mice are capable of
discriminating intensities across frequencies and sensation levels, but have
higher intensity difference limens (IDLs) thresholds than other mammals.
PMID- 29341907
TI - Molecular-level elucidation of saccharin-assisted rapid dissolution and high
supersaturation level of drug from Eudragit(r) E solid dispersion.
AB - In this work, the effect of saccharin (SAC) addition on the dissolution and
supersaturation level of phenytoin (PHT)/Eudragit(r) E (EUD-E) solid dispersion
(SD) at neutral pH was examined. The PHT/EUD-E SD showed a much slower
dissolution of PHT compared to the PHT/EUD-E/SAC SD. EUD-E formed a gel layer
after the dispersion of the PHT/EUD-E SD into an aqueous medium, resulting in a
slow dissolution of PHT. Pre-dissolving SAC in the aqueous medium significantly
improved the dissolution of the PHT/EUD-E SD. Solid-state 13C NMR measurements
showed an ionic interaction between the tertiary amino group of EUD-E and the
amide group of SAC in the EUD-E gel layer. Consequently, the ionized EUD-E could
easily dissolve from the gel layer, promoting PHT dissolution. Solution-state 1H
NMR measurements revealed the presence of ionic interactions between SAC and the
amino group of EUD-E in the PHT/EUD-E/SAC solution. In contrast, interactions
between PHT and the hydrophobic group of EUD-E strongly inhibited the
crystallization of the former from its supersaturated solution. The PHT
supersaturated solution was formed from the PHT/EUD-E/SAC SD by the fast
dissolution of PHT and the strong crystallization inhibition effect of EUD-E
after aqueous dissolution.
PMID- 29341908
TI - Induction of Au-methotrexate conjugates by sugar molecules: production, assembly
mechanism, and bioassay studies.
AB - Au-methotrexate (Au-MTX) conjugates induced by sugar molecules were produced by a
simple, one-pot, hydrothermal growth method. Herein, the Au(III)-MTX complexes
were used as the precursors to form Au-MTX conjugates. Addition of different
types of sugar molecules with abundant hydroxyl groups resulted in the formation
of Au-MTX conjugates featuring distinct characteristics that could be explained
by the diverse capping mechanisms of sugar molecules. That is, the instant
capping mechanism of glucose favored the generation of peanut-like Au-MTX
conjugates with high colloidal stability while the post-capping mechanism of
dextran and sucrose resulted in the production of Au-MTX conjugates featuring
excellent near-infrared (NIR) optical properties with a long-wavelength plasmon
resonance near 630-760 nm. Moreover, in vitro bioassays showed that cancer cell
viabilities upon incubation with free MTX, Au-MTX conjugates doped with glucose,
dextran and sucrose for 48 h were 74.6%, 55.0%, 62.0%, and 63.1%, respectively.
Glucose-doped Au-MTX conjugates exhibited a higher anticancer activity than those
doped with dextran and sucrose, therefore potentially presenting a promising
treatment platform for anticancer therapy. Based on the present study, this work
may provide the first example of using biocompatible sugars as regulating agents
to effectively guide the shape and assembly behavior of Au-MTX conjugates.
Potentially, the synergistic strategy of drug molecules and sugar molecules may
offer the possibility to create more gold-based nanocarriers with new shapes and
beneficial features for advanced anticancer therapy.
PMID- 29341909
TI - Nanogel-DFO conjugates as a model to investigate pharmacokinetics,
biodistribution, and iron chelation in vivo.
AB - Deferoxamine (DFO) to treat iron overload (IO) has been limited by toxicity
issues and short circulation times and it would be desirable to prolong
circulation to improve non-transferrin bound iron (NTBI) chelation. In addition,
DFO is currently unable to efficiently target the large pool of iron in the liver
and spleen. Nanogel-Deferoxamine conjugates (NG-DFO) can prove useful as a model
to investigate the pharmacokinetic (PK) properties and biodistribution (BD)
behavior of iron-chelating macromolecules and their overall effect on serum
ferritin levels. NG-DFO reduced the cytotoxicity of DFO and significantly reduced
cellular ferritin levels in IO macrophages in vitro. PK/BD studies in normal rats
revealed that NG-DFO displayed prolonged circulation and preferential
accumulation into the liver and spleen. IO mice treated with NG1-DFO presented
significantly lower levels of serum ferritin compared to DFO. Total renal and
fecal elimination data point to the need to balance prolonged circulation with
controlled degradation to accelerate clearance of iron-chelating macromolecules.
PMID- 29341910
TI - Isomalt and its diastereomer mixtures as stabilizing excipients with freeze-dried
lactate dehydrogenase.
AB - The purpose of this research was to study isomalt as a protein-stabilizing
excipient with lactate dehydrogenase (LDH) during freeze-drying and subsequent
storage and compare it to sucrose, a standard freeze-drying excipient. Four
different diastereomer mixtures of isomalt were studied. The stability of the
protein was studied with a spectrophotometric enzyme activity test and circular
dichroism after freeze-drying and after 21 days of storage at 16% RH. Physical
stability was analyzed with differential scanning calorimetry and Karl Fischer
titration. Statistical analysis was utilized in result analysis. LDH activity was
almost completely retained after freeze-drying with sucrose; whereas samples
stabilized with isomalt diastereomer mixtures had a considerably lower protein
activity. During storage the sucrose-containing samples lost most of their
enzymatic activity, while the isomalt mixtures retained the protein activity
better. In all cases changes to protein secondary structure were observed.
Isomalt diastereomer mixtures have some potential as protein-stabilizing
excipients during freeze-drying and subsequent storage. Isomalt stabilized LDH
moderately during freeze-drying; however it performed better during storage.
Future studies with other proteins are required to evaluate more generally
whether isomalt would be a suitable excipient for pharmaceutical freeze-dried
protein formulations.
PMID- 29341911
TI - An efficient PEGylated gene delivery system with improved targeting: Synergism
between octaarginine and a fusogenic peptide.
AB - Because of their ability to translocate different cargos into cells, arginine
rich cell penetrating peptides (CPPs) are promising vehicles for drug and gene
delivery. The use of CPP-based carriers, however, is hampered by the lack of
specificity and by interactions with negative serum components. Polyethylene
glycol (PEG) is used to decrease such non-specific interactions, albeit its use
is associated with reduced transfection efficiency. In this study, we describe
the development of PEGylated CPP-based gene carrier with an improved targeting
and a high transfection activity. The system was prepared by condensing DNA with
a polycation followed by coating with a lipid envelope containing the
octaarginine (R8) peptide as a model CPP. R8-modified nanoparticles produced high
transfection activities, but the efficiency was reduced by PEG shielding. The
reduced activity could be fully restored by the addition of a targeting ligand
and a pH-sensitive fusogenic peptide. The efficiency of the proposed system is
quite high, even in the presence of serum, and shows improved targeting and
selectivity. Surprisingly, the effect of the fusogenic peptide was dramatically
reduced in the absence of R8. Although shielded, R8 augmented the activity of the
fusogenic peptide, suggesting a synergistic effect between the two peptides at
the intracellular level.
PMID- 29341912
TI - Quantitative estimation of phenytoin sodium disproportionation in the
formulations using vibration spectroscopies and multivariate methodologies.
AB - Phenytoin sodium (PS) has a tendency to convert to its base form; phenytoin base
(PHT) during manufacturing, packaging, shelf life and in-use conditions that can
influence its clinical performance. The objective of the present work was to
develop a non-destructive, quick and easy analytical method for quantification of
PHT in the drug product. A formulation was prepared to contain the excipients of
commercial capsule formulation of PS. The formulation containing either 100% PHT
or PS was prepared and these formulations were mixed in different proportion to
achieve 0-100% PHT matrices. FTIR, NIR and Raman spectra of samples were
collected. Data were truncated and mathematically pretreated before development
of partial least squares (PLS) and principal component analysis (PCA) regressions
model. The models were assessed by slope, intercept, R, R2, root mean square
error (RMSE) and standard error (SEP). The models exhibited good linearity over
the selected range of PHT in the formulations with low error as indicated by
slope that was close to one and small values of intercept, RMSE and SE. The
models of NIR based data were more accurate and precise than Raman data based
models as indicated by the low values of RMSE and SE. Prediction accuracy of
independent samples containing 25% PHT using NIR models were similar to Raman
models. On the other hand, the prediction was more precise for the independent
sample containing 5% PHT using NIR data based models compared to Raman data based
models as indicated by standard deviation. In conclusion, chemometric models
based on NIR and Raman spectroscopies provides a fast and easy way to monitor the
disproportionation of PS in the drug products.
PMID- 29341913
TI - Characterisation of pore structures of pharmaceutical tablets: A review.
AB - Traditionally, the development of a new solid dosage form is formulation-driven
and less focus is put on the design of a specific microstructure for the drug
delivery system. However, the compaction process particularly impacts the
microstructure, or more precisely, the pore architecture in a pharmaceutical
tablet. Besides the formulation, the pore structure is a major contributor to the
overall performance of oral solid dosage forms as it directly affects the liquid
uptake rate, which is the very first step of the dissolution process. In future,
additive manufacturing is a potential game changer to design the inner structures
and realise a tailor-made pore structure. In pharmaceutical development the pore
structure is most commonly only described by the total porosity of the tablet
matrix. Yet it is of great importance to consider other parameters to fully
resolve the interplay between microstructure and dosage form performance.
Specifically, tortuosity, connectivity, as well as pore shape, size and
orientation all impact the flow paths and play an important role in describing
the fluid flow in a pharmaceutical tablet. This review presents the key
properties of the pore structures in solid dosage forms and it discusses how to
measure these properties. In particular, the principles, advantages and
limitations of helium pycnometry, mercury porosimetry, terahertz time-domain
spectroscopy, nuclear magnetic resonance and X-ray computed microtomography are
discussed.
PMID- 29341914
TI - Is there a correlation between the glass forming ability of a drug and its
supersaturation propensity?
AB - The use of an enabling formulation technique, such as amorphization of a poorly
water-soluble crystalline drug, can result in supersaturation with respect to the
crystalline form of the drug and thus potentially in a higher degree of
absorption after oral administration. The ease with which such drugs can be
amorphized is known as their glass forming ability (GFA). In this study, a
potential correlation between GFA and supersaturation propensity is investigated.
The GFA of 23 different drugs was determined by melt quenching or milling the
crystalline drugs to obtain their respective amorphous forms. The inherent
propensity of the drug to supersaturate, i.e. the maximal apparent degree of
supersaturation (aDS), and the time until precipitation at a given aDS were
determined. Supersaturation was induced via a solvent shift method where the drug
was initially dissolved in dimethyl sulfoxide and then added to a biorelevant
medium (fasted state simulated intestinal fluid).The study showed that drugs
which are good glass formers also have the potential to supersaturate to a high
degree (high maximal aDS) whereas drugs that are modest glass formers
supersaturate only to a low degree. This correlation was confirmed by principal
component analysis, which also indicated that melt enthalpy inversely correlated
with both GFA and maximal aDS. However, no correlation between GFA of a drug and
the time until precipitation at a given aDS was found.
PMID- 29341915
TI - Influence of ligands property and particle size of gold nanoparticles on the
protein adsorption and corresponding targeting ability.
AB - Nanoparticulated vesicles were widely used for carriers of drugs and imaging
probes. To improve the targeting delivery efficiency of these vesicles, ligands
were often functionalized onto their surfaces. However, the interaction between
vesicles and plasma proteins may cover the ligands and hinder the targeting
delivery. It is important to address the potential influence of ligands
modification on plasma protein adsorption and the following targeting delivery.
In this study, two common used ligands were chosen as the model: transferrin and
RGD peptide. Gold nanoparticles were utilized as model particles. Sodium dodecyl
sulfate polyacrylamide gel electrophoresis data demonstrated that higher PEG
modification and smaller particle size could reduce the plasma protein
adsorption, while ligand modification could increase. The cellular uptake results
showed that the targeting ability of smaller ligand RGD peptide would be more
easily influenced by the proteins corona.
PMID- 29341916
TI - Effects of surfactant-based permeation enhancers on mannitol permeability,
histology, and electrogenic ion transport responses in excised rat colonic
mucosae.
AB - Surfactant-based intestinal permeation enhancers (PEs) are constituents of
several oral macromolecule formulations in clinical trials. This study examined
the interaction of a test panel of surfactant-based PEs with isolated rat colonic
mucosae mounted in Ussing chambers in an attempt to determine if increases in
transepithelial permeability can be separated from induction of mucosal
perturbation. The aim was to assess the effects of PEs on (i) apparent
permeability coefficient (Papp) of [14C]-mannitol (ii) histology score and (iii)
short-circuit current (DeltaIsc) responses to a cholinomimetic (carbachol, CCh).
Enhancement ratio increases for Papp values followed the order: C10 > C9 = C11:1
> a bile salt blend > sodium choleate > sucrose laurate > Labrasol(r) >C12E8 >
C12 > Cremophor(r) A25 > C7 > sucrose stearate > Kolliphor(r) HS15 > Kolliphor(r)
TPGS. Exposures that increased the Papp by >=2-fold over 120 min were accompanied
by histological damage in 94% of tissues, and by a decreased DeltaIsc response to
CCh in 83%. A degree of separation between the increased Papp of [14C]-mannitol
and histological damage and diminution of the DeltaIsc response to CCh was
observed at selected concentrations of Labrasol(r). Overall, this surfactant
based PE selection caused transcellular perturbation at similar concentrations to
those that enhanced permeability.
PMID- 29341917
TI - A novel method for the production of core-shell microparticles by inverse
gelation optimized with artificial intelligent tools.
AB - Numerous studies have been focused on hydrophobic compounds encapsulation as
oils. In fact, oils can provide numerous health benefits as synergic ingredient
combined with other hydrophobic active ingredients. However, stable
microparticles for pharmaceutical purposes are difficult to achieve when commonly
techniques are used. In this work, sunflower oil was encapsulated in calcium
alginate capsules by prilling technique in co-axial configuration. Core-shell
beads were produced by inverse gelation directly at the nozzle using a w/o
emulsion containing aqueous calcium chloride solution in sunflower oil pumped
through the inner nozzle while an aqueous alginate solution, coming out from the
annular nozzle, produced the beads shell. To optimize process parameters
artificial intelligence tools were proposed to optimize the numerous prilling
process variables. Homogeneous and spherical microcapsules with narrow size
distribution and a thin alginate shell were obtained when the parameters as w/o
constituents, polymer concentrations, flow rates and frequency of vibration were
optimized by two commercial software, FormRules(r) and INForm(r), which implement
neurofuzzy logic and Artificial Neural Networks together with genetic algorithms,
respectively. This technique constitutes an innovative approach for hydrophobic
compounds microencapsulation.
PMID- 29341918
TI - Asymmetric flow field flow fractionation for the characterization of globule size
distribution in complex formulations: A cyclosporine ophthalmic emulsion case.
AB - Commonly used characterization techniques such as cryogenic-transmission electron
microscopy (cryo-TEM) and batch-mode dynamic light scattering (DLS) are either
time consuming or unable to offer high resolution to discern the poly-dispersity
of complex drug products like cyclosporine ophthalmic emulsions. Here, a size
based separation and characterization method for globule size distribution using
an asymmetric flow field flow fractionation (AF4) is reported for comparative
assessment of cyclosporine ophthalmic emulsion drug products (model formulation)
with a wide size span and poly-dispersity. Cyclosporine emulsion formulations
that are qualitatively (Q1) and quantitatively (Q2) the same as Restasis(r) were
prepared in house with varying manufacturing processes and analyzed using the
optimized AF4 method. Based on our results, the commercially available
cyclosporine ophthalmic emulsion has a globule size span from 30 nm to a few
hundred nanometers with majority smaller than 100 nm. The results with in-house
formulations demonstrated the sensitivity of AF4 in determining the differences
in the globule size distribution caused by the changes to the manufacturing
process. It is concluded that the optimized AF4 is a potential analytical
technique for comprehensive understanding of the microstructure and assessment of
complex emulsion drug products with high poly-dispersity.
PMID- 29341919
TI - Performance of an acoustically mixed pharmaceutical dry powder delivered from a
novel inhaler.
PMID- 29341920
TI - Effect of structural factors on release profiles of camptothecin from block
copolymer conjugates with high load of drug.
AB - The aim of the present work was the synthesis and study the kinetics and profiles
of camptothecin (CPT) release form block co- and ter-polymer conjugates
comprising polylactide (PLA) segments and CPT moieties, structurally diverse by
degrees of branching, content of d-PLA units and poly(ethylene glycol) methyl
ether methacrylate (PEGMA). Six PLA, non-toxic macroinitiators (MIs), terminated
with alpha-bromoester were synthesized. MIs were subjected to polymerization of
CPT methacrylic derivative (CPTMA) with PEGMA at various ratios. The average
contents of CPT from elemental analysis, NMR and UV-GPC were approximate to each
other. The number of CPT molecules and PEGMA units was in the range of 9-195 and
0-280 per conjugate, respectively. PEGMA units plasticized PLA causing increase
of its crystallinity, whereas 7% and more of d-PLA caused material amorphous.
PEGMA units decreased thermal stability of conjugates, however it compatibillized
the separated phases of PLA and PCPTMA, based on AFM. In vitro release rate of
CPT from linear PLA conjugates deposited on injection-molded PLA bars increased
by introduction of PEGMA units with zero-order kinetics and Korsmeyer-Peppas
model indicating the super case II transport. Branched conjugates revealed some
burst release and then the release was rather of first-order-kinetics with
respect to CPT with non-Fickian transport.
PMID- 29341921
TI - Computational hydrodynamic comparison of a mini vessel and a USP 2 dissolution
testing system to predict the dynamic operating conditions for similarity of
dissolution performance.
AB - The hydrodynamic characteristics of a mini vessel and a USP 2 dissolution testing
system were obtained and compared to predict the tablet-liquid mass transfer
coefficient from velocity distributions near the tablet and establish the dynamic
operating conditions under which dissolution in mini vessels could be conducted
to generate concentration profiles similar to those in the USP 2. Velocity
profiles were obtained experimentally using Particle Image Velocimetry (PIV).
Computational Fluid Dynamics (CFD) was used to predict the velocity distribution
and strain rate around a model tablet. A CFD-based mass transfer model was also
developed. When plotted against strain rate, the predicted tablet-liquid mass
transfer coefficient was found to be independent of the system where it was
obtained, implying that a tablet would dissolve at the same rate in both systems
provided that the concentration gradient between the tablet surface and the bulk
is the same, the tablet surface area per unit liquid volume is identical, and the
two systems are operated at the appropriate agitation speeds specified in this
work. The results of this work will help dissolution scientists operate mini
vessels so as to predict the dissolution profiles in the USP 2, especially during
the early stages of drug development.
PMID- 29341922
TI - Sustained release timolol maleate loaded ocusert based on biopolymer composite.
AB - In the present investigation, the effect of timolol maleate loaded ocuserts was
studied as an alternative for conventional anti-glaucoma formulation. Ocuserts
were prepared using natural polymer sodium alginate and ethyl cellulose. Physico
chemical properties along with drug entrapment efficiency (94-98%), content
uniformity (93.1% +/- 0.264-98.00% +/- 0.321), in vitro drug release (83.42% +/-
0.35 at end of 12 h), ex vivo permeation all showed satisfactory results, which
was found to follow zero order kinetics. Ex vivo permeation studies showed better
results, revealed that the permeability coefficient was dependent on polymer
type. The sterility test accelerated stability studies and in vivo studies such
as eye irritancy test, in vivo drug release of the optimized ocusert was
determined. The anti-glaucoma activity was measured using Schiotz tonometer at
different time interval. Significant reduction in Intra ocular pressure (IOP)
within 3 days was observed in case of rabbits treated with ocusert in comparison
to the rabbit treated with marketed eye drop formulation. Hence timolol maleate
loaded ocuserts proved to be a promising and viable alternative over conventional
eye formulation for the sustained and controlled ophthalmic drug delivery,
targeting the drug within the ocular globe thus improving patient compliance for
the treatment of glaucoma.
PMID- 29341923
TI - Purification, chitooligosaccharide binding properties and thermal stability of
CIA24, a new PP2-like phloem exudate lectin from ivy gourd (Coccinia indica).
AB - PP2-like chitin binding phloem exudate lectins, abundant in the sieve tube of
cucurbits, have been implicated to play key roles in wound sealing and
antipathogenic responses of the plant. Here we report the affinity purification,
macromolecular characterization and carbohydrate binding properties of a new
chitooligosaccharide-specific lectin from the phloem exudate of ivy gourds
(Coccinia indica). The protein, CIA24, has a subunit mass of 24 kDa. Partial
sequence analysis indicated that CIA24 exhibits high homology with CIA17 and
other Cucurbitaceae PP2 proteins whereas CD spectroscopic studies suggested that
beta-sheets constitute the predominant secondary structure. Temperature dependent
CD spectroscopic and differential scanning calorimetric studies revealed that
CIA24 is a highly thermostable protein, which undergoes complete unfolding at
~105 degrees C. Isothermal titration calorimetric studies suggested that binding
of chitooligosaccharides to CIA24 is a highly exothermic process. The lectin
combining site can accommodate upto a tetrasaccharide with the binding
stoichiometry (n) close to unity with respect to each protein subunit, whereas
for chitohexaose a sharp decrease in the binding stoichiometry (n) to ~1:0.5 was
observed. This suggests that the protein probably undergoes dimerisation in
presence of chitohexaose, wherein two protein molecules bind to the
oligosaccharides from the reducing and non-reducing end, respectively.
PMID- 29341924
TI - Maca polysaccharides: A review of compositions, isolation, therapeutics and
prospects.
AB - Maca polysaccharides, some of the major bioactive substances in Lepidium meyenii
(Walp.) (Maca), have various biological properties, including anti-oxidant, anti
fatigue, anti-tumor, and immunomodulatory effects, as well as hepatoprotective
activity and regulation function. Although many therapeutics depend on multiple
structures of maca polysaccharides in addition to providing sufficient
foundations for maca polysaccharide products in industrial applications, the
relationships between the pharmacological effects and structures have not been
established. Therefore, this article summarizes the extraction and purification
methods, compositions, pharmacological effects, prospects and industrial
applications of maca polysaccharides.
PMID- 29341925
TI - Phase contrast tomography at lab on chip scale by digital holography.
AB - High-throughput single-cell analysis is a challenging target for implementing
advanced biomedical applications. An excellent candidate for this aim is label
free tomographic phase microscopy (TPM). In this paper, some of the methods used
to obtain TPM are reviewed, analyzing advantages and disadvantages of each of
them. Moreover, an alternative tomographic technique is described for live cells
analysis, and future trends of the method are foreseen. In particular, by
exploiting random rolling of cells while they are flowing along a microfluidic
channel, it is possible to obtain phase-contrast tomography thus obtaining
complete retrieval of both 3D-position and orientation of rotating cells. Thus, a
priori knowledge of such information is no longer needed. This approach extremely
simplifies the optical system avoiding any mechanical/optical scanning of light
source. The proof is given for different classes of biosamples, red-blood-cells
(RBCs) and diatom algae. Accurate characterization of each type of cells is
reported and compared to that obtained by other tomographic techniques.
PMID- 29341926
TI - Direct detection of carbon and nitrogen nuclei for high-resolution analysis of
intrinsically disordered proteins using NMR spectroscopy.
AB - Nuclear magnetic resonance spectroscopy (NMR) is a powerful technique for
characterizing the structural and dynamic properties of intrinsically disordered
proteins and protein regions (IDPs & IDRs). However, the application of NMR to
IDPs has been limited by poor chemical shift dispersion in two-dimensional (2D)
1H-15N heteronuclear correlation spectra. Among the various detection schemes
available for heteronuclear correlation spectroscopy, 13C direct-detection has
become a mainstay for investigations of IDPs owing to the favorable chemical
shift dispersion in 2D 13C'-15N correlation spectra. Recent advances in cryoprobe
technology have enhanced the sensitivity for direct detection of both 13C and 15N
resonances at high magnetic field strengths, thus prompting the development of
15N direct-detect experiments to complement established 13C-detection
experiments. However, the application of 15N-detection has not been widely
explored for IDPs. Here we compare 1H, 13C, and 15N detection schemes for a
variety of 2D heteronuclear correlation spectra and evaluate their performance on
the basis of resolution, chemical shift dispersion, and sensitivity. We performed
experiments with a variety of disordered systems ranging in size and complexity;
from a small IDR (99 amino acids), to a large low complexity IDR (185 amino
acids), and finally a ~73 kDa folded homopentameric protein that also contains
disordered regions (133 amino acids/monomer). We conclude that, while requiring
high sample concentration and long acquisition times, 15N-detection often offers
enhanced resolution over other detection schemes in studies of disordered protein
regions with low complexity sequences.
PMID- 29341927
TI - Book lung development in juveniles and adults of the cobweb spider, Parasteatoda
tepidariorum C. L. Koch, 1841 (Araneomorphae, Theridiidae).
AB - Light and transmission electron microscopy were used to study the development of
new book lung lamellae in juvenile and adult spiders (Parasteatoda tepidariorum).
As hypothesized earlier in a study of embryos, mesenchyme cells dispersed
throughout the opisthosoma (EMT) are a likely source of precursor epithelial
cells (MET) for the new lamellae. The precursor cells in juveniles and adults
continue many of the complex activities observed in embryos, e.g., migration,
alignment, lumen formation, thinning, elongation, and secretion of the cuticle of
air channel walls and trabeculae. The apicobasal polarity of precursor cells for
new channels is apparently induced by the polarity pattern of precursor cells of
channels produced earlier. Thus, new air and hemolymph channels extend and
continue the alternating pattern of older channels. At sites more distant from
the spiracle and atrium, new channels are usually produced by the mode II process
(intracellular alignment and merging of vesicles). These air channels have
bridging trabeculae and are quite stable in size throughout their length. At
sites closer to the spiracle and atrium, new channels may be produced by mode I
(coalescence of merocrine vesicle secretion). This raises the hypothesis that
structural and functional differences in mode I and II channels and differing
oxygen and fluid conditions with distance from the spiracle and atrium determine
the mode of formation of new channels. Observations herein support an earlier
hypothesis that there is some intercellular apical/apical and basal/basal
affinity among the opposed surfaces of aligned precursor cells. This results in
the alternating pattern of air channels at the apical and hemolymph channels at
the basal cell surfaces.
PMID- 29341929
TI - The infection of red seabream iridovirus in mandarin fish (Siniperca chuatsi) and
the host immune related gene expression profiles.
AB - Red Sea bream iridovirus (RSIV) was initially isolated from marine fish, which
belongs to Megalocytivirus, Iridoviridae. It can cause great economic losses in
fish culture with high morbidity and mortality. In the present study, the
pathogenicity and immune response associated with a RSIV genotype megalocytivirus
infection were determined in mandarin fish (Siniperca chuatsi). Fish challenged
showed typical clinical signs of iridovirus infection, including acute
haemorrhages and enlarged visceral organs. Histopathological analysis revealed
that extensive necrosis, vacuolization and inflammation were presented in the
stomach, spleen, kidney and liver of the diseased fish. Blood cells counting and
phagocytic assay indicated that the numbers of the red and white blood cells in
the peripheral blood of infected fish increased significantly compared to the
control group and the phagocytic percentage of leukocytes peaked at day 6 post
infection. Quantitive real-time PCR (qRT-PCR) was also undertaken to analyse the
host defensive response in mandarin fish challenged with RSIV. The expression
level of ten genes including interferon-related factors (IRFs) IRF1 and IRF7, Mx,
Viperin, JAK1, STAT1, TCRalpha, TNFalpha, IL-1beta and IL-8 during experimental
infection were monitored at different point of time in liver, spleen and head
kidney. Results revealed varying expression profiles and clear transcriptional
activation of these immune related genes in different tissues, which will
contribute to better understand the pathogenesis and host defensive system in
iridovirus invasion.
PMID- 29341930
TI - Activation of estrogen receptor beta (ERbeta) regulates the expression of N
cadherin, E-cadherin and beta-catenin in androgen-independent prostate cancer
cells.
AB - The aim of the present study was to investigate the impact of the activation of
estrogen receptors on expression and localization of N-cadherin, E-cadherin and
non-phosphorylated beta-catenin in androgen-independent prostate cancer cells (PC
3 and DU-145) and in human post pubertal prostate epithelial cells (PNT1A).
Expression of N-cadherin was detected in PNT1A and PC-3 cells, but not in DU-145
cells. E-cadherin was detected only in DU-145 cells and beta-catenin was detected
in all cells studied. N-cadherin and beta-catenin were located preferentially in
the cellular membrane of PNT1A cells and in the cytoplasm of PC-3 cells. E
cadherin and beta-catenin were located preferentially in the cellular membrane of
DU-145 cells. 17beta-estradiol (E2) or the ERalpha-selective agonist PPT did not
affect the content and localization of N-cadherin in PC-3 and PNT1A cells or E
cadherin in DU-145 cells. In PC-3 cells, ERbeta-selective agonist DPN decreased
the expression of N-cadherin. DPN-induced downregulation of N-cadherin was
blocked by pretreatment with the ERbeta-selective antagonist (PHTPP), indicating
that ERbeta1 is the upstream receptor regulating the expression of N-cadherin. In
DU-145 cells, the activation of ERbeta1 by DPN increased the expression of E
cadherin. Taken together, these results suggest that activation of ERbeta1 is
required to maintain an epithelial phenotype in PC-3 and DU-145 cells. The
activation of ERbeta1 also increased the expression of beta-catenin in cytoplasm
of PC-3 and in the cellular membrane of DU-145 cells. In conclusion, our results
indicate differential expression and localization of N-cadherin, E-cadherin and
beta-catenin in androgen-independent prostate cancer cells. The reduction of N
cadherin content by activation of ERbeta, exclusively observed in androgen
independent prostate cancer cells (PC-3), may be related to the activation of
signaling pathways, such as the release of beta-catenin into the cytoplasm,
translocation of beta-catenin to the nucleus and activation of gene
transcription.
PMID- 29341928
TI - A novel brown adipocyte-enriched long non-coding RNA that is required for brown
adipocyte differentiation and sufficient to drive thermogenic gene program in
white adipocytes.
AB - The thermogenic activities of brown and beige adipocytes can be exploited to
reduce energy surplus and counteract obesity. Recent RNA sequencing studies have
uncovered a number of long noncoding RNAs (lncRNAs) uniquely expressed in white
and brown adipose tissues (WAT and BAT), but whether and how these lncRNAs
function in adipogenesis remain largely unknown. Here, we report the
identification of a novel brown adipocyte-enriched LncRNA (AK079912), and its
nuclear localization, function and regulation. The expression of AK079912
increases during brown preadipocyte differentiation and in response to cold
stimulated browning of white adipocytes. Knockdown of AK079912 inhibits brown
preadipocyte differentiation, manifested by reductions in lipid accumulation and
down-regulation of adipogenic and BAT-specific genes. Conversely, ectopic
expression of AK079912 in white preadipocytes up-regulates the expression of
genes involved in thermogenesis. Mechanistically, inhibition of AK079912 reduces
mitochondrial copy number and protein levels of mitochondria electron transport
chain (ETC) complexes, whereas AK079912 overexpression increases the levels of
ETC proteins. Lastly, reporter and pharmacological assays identify Ppargamma as
an upstream regulator of AK079912. These results provide new insights into the
function of non-coding RNAs in brown adipogenesis and regulating browning of
white adipocytes.
PMID- 29341931
TI - Bioinspired capsules based on nanocellulose, xyloglucan and pectin - The
influence of capsule wall composition on permeability properties.
AB - : Materials based on renewable biopolymers, selective permeability and stimuli
responsive release/loading properties play an important role in biomedical
applications. Here, in order to mimic the plant primary cell-wall, microcapsules
have been fabricated using cell wall polysaccharides, namely pectin, xyloglucan
and cellulose nanofibers. For the first time, a large amount of xyloglucan was
successfully included in such capsules. These capsules demonstrated stimuli
responsive (ON/OFF) permeability and biocompatibility. The live cell staining
revealed that the microcapsules' surface enhanced cell growth and also the non
toxic nature of the microcapsules. In water, the microcapsules were completely
and partially permeable to fluorescent dextrans with an average molecular weight
of 70 kDa (hydrodynamic diameter of ca. 12 nm) and 2000 kDa (ca. 54 nm),
respectively. On the other hand, the permeability dropped quickly when the
capsules were exposed to 250 mM NaCl solution, trapping a fraction of the 70 kDa
dextrans in the capsule interior. The decrease in permeability was a direct
consequence of the capsule-wall composition, i.e. the presence of xyloglucan and
a low amount of charged molecules such as pectin. The low permeability of
capsules in saline conditions (and in a model biological medium), combined with a
capsule wall that is made from dietary fibers only, potentially enables their use
in biological applications, such as colon targeted delivery in the gastro
intestinal tract. STATEMENT OF SIGNIFICANCE: For the first time, microcapsules
have been prepared that possess capsule walls that mimic the primary cell wall
found in natural plant cells. The capsules were assembled using pectin,
xyloglucan and cellulose in the form of cellulose nanofibers. The capsules
demonstrated stimuli-responsive (ON/OFF) permeability and biocompatibility. The
low permeability of capsules in saline conditions (and in a model biological
medium), combined with a capsule wall that is made from dietary fibers only,
potentially enables their use in biological applications, such as colon targeted
delivery in the gastro-intestinal tract. Such model plant cell capsules might
also further improve the understanding for the digestion and release of nutrients
from natural plant cells found in vegetables and fruits.
PMID- 29341932
TI - Synthetic extracellular matrix mimic hydrogel improves efficacy of mesenchymal
stromal cell therapy for ischemic cardiomyopathy.
AB - BACKGROUND: Mesenchymal stromal cells (MSC) repair infarcted hearts mainly
through paracrine mechanisms. Low cell engraftment limits the release of soluble
paracrine factors (SF) over time and, consequently, MSC efficacy. We tested
whether a synthetic extracellular matrix mimic, a hydrogel containing heparin (H
HG), could ameliorate MSC engraftment and binding/release of SF, thus improving
MSC therapy efficacy. METHODS AND RESULTS: In vitro, rat bone-marrow MSC (rBM
MSC) were seeded and grown into H-HG. Under normoxia, the hydrogel did not affect
cell survival (rBM-MSC survival >90% at each time point tested); vice versa,
under hypoxia the biomaterial resulted to be protective for the cells (p < .001
vs rBM-MSC alone). H-HG or control PEG hydrogels (HG) were incubated with VEGF or
bFGF for binding/release quantification. Data showed significantly higher amount
of VEGF and bFGF bound by H-HG compared with HG (p < .05) and a constant release
over time. In vivo, myocardial infarction (MI) was induced in female Sprague
Dawley rats by permanent coronary ligation. One week later, saline, rBM-MSC, H-HG
or rBM-MSC/H-HG were injected in the infarct zone. The co-injection of rBM-MSC/H
HG into infarcted hearts significantly increased cardiac function. Importantly,
we observed a significant gain in MSC engraftment, reduction of ventricular
remodeling and stimulation of neo-vasculogenesis. We also documented higher
amounts of several pro-angiogenic factors in hearts treated with rBM-MSC/H-HG.
CONCLUSIONS: Our data show that H-HG increases MSC engraftment, efficiently fine
tunes the paracrine MSC actions and improves cardiac function in infarcted rat
hearts. STATEMENT OF SIGNIFICANCE: Transplantation of MSC is a promising
treatment for ischemic heart disease, but low cell engraftment has so far limited
its efficacy. The enzymatically degradable H-HG that we developed is able to
increase MSC retention/engraftment and, at the same time, to fine-tune the
paracrine effects mediated by the cells. Most importantly, the co-transplantation
of MSC and H-HG in a rat model of ischemic cardiomyopathy improved heart function
through a significant reduction in ventricular remodeling/scarring and
amelioration in neo-vasculogenesis/endogenous cardiac regeneration. These
beneficial effects are comparable to those obtained by others using a much
greater number of cells, strengthening the efficacy of the biomaterial used in
increasing the therapeutic effects of MSC. Given its efficacy and safety,
documented by the absence of immunoreaction, our strategy appears readily
translatable to clinical scenarios.
PMID- 29341933
TI - The effects of platelet lysate patches on the activity of tendon-derived cells.
AB - : Platelet-derived biomaterials are widely explored as cost-effective sources of
therapeutic factors, holding a strong potential for endogenous regenerative
medicine. Particularly for tendon repair, treatment approaches that shift the
injury environment are explored to accelerate tendon regeneration. Herein,
genipin-crosslinked platelet lysate (PL) patches are proposed for the delivery of
human-derived therapeutic factors in patch augmentation strategies aiming at
tendon repair. Developed PL patches exhibited a controlled release profile of PL
proteins, including bFGF and PDGF-BB. Additionally, PL patches exhibited an
antibacterial effect by preventing the adhesion, proliferation and biofilm
formation by S. aureus, a common pathogen in orthopaedic surgical site
infections. Furthermore, these patches supported the activity of human tendon
derived cells (hTDCs). Cells were able to proliferate over time and an up
regulation of tenogenic genes (SCX, COL1A1 and TNC) was observed, suggesting that
PL patches may modify the behavior of hTDCs. Accordingly, hTDCs deposited tendon
related extracellular matrix proteins, namely collagen type I and tenascin C. In
summary, PL patches can act as a reservoir of biomolecules derived from PL and
support the activity of native tendon cells, being proposed as bioinstructive
patches for tendon regeneration. STATEMENT OF SIGNIFICANCE: Platelet-derived
biomaterials hold great interest for the delivery of therapeutic factors for
applications in endogenous regenerative medicine. In the particular case of
tendon repair, patch augmentation strategies aiming at shifting the injury
environment are explored to improve tendon regeneration. In this study, PL
patches were developed with remarkable features, including the controlled release
of growth factors and antibacterial efficacy. Remarkably, PL patches supported
the activity of native tendon cells by up-regulating tenogenic genes and enabling
the deposition of ECM proteins. This patch holds great potential towards
simultaneously reducing post-implantation surgical site infections and promoting
tendon regeneration for prospective in vivo applications.
PMID- 29341934
TI - Advances in the delivery of antisense oligonucleotides for combating bacterial
infectious diseases.
AB - Discovery and development of new antibacterial drugs against multidrug resistant
bacterial strains have become more and more urgent. Antisense oligonucleotides
(ASOs) show immense potential to control the spread of resistant microbes due to
its high specificity of action, little risk to human gene expression, and easy
design and synthesis to target any possible gene. However, efficient delivery of
ASOs to their action sites with enough concentration remains a major obstacle,
which greatly hampers their clinical application. In this study, we reviewed
current progress on delivery strategies of ASOs into bacteria, focused on various
non-virus gene vectors, including cell penetrating peptides, lipid nanoparticles,
bolaamphiphile-based nanoparticles, DNA nanostructures and Vitamin B12. The
current review provided comprehensive understanding and novel perspective for the
future application of ASOs in combating bacterial infections.
PMID- 29341935
TI - Systemic Sclerosis: Small mouth, big burden?
PMID- 29341936
TI - Rheumatic manifestations among cancer patients treated with immune checkpoint
inhibitors.
AB - BACKGROUND: The use of immune checkpoint inhibitors (ICI) has grown incessantly
since they were first approved in 2014. These monoclonal antibodies inhibit T
cell activation, yielding a dramatic tumor response with improved survival.
However, immunotherapy is frequently hampered by immune adverse events (iAE) such
as hypophysitis, colitis, hepatitis, pneumonitis and rash. Until recently,
rheumatic side effects were only infrequently reported. AIM: To describe the
rheumatic manifestations encountered among patients treated with ICIs in a large
tertiary cancer center in Israel METHODS: The cancer center's patient registry
was screened for patients who had ever been treated with ipilimumab,
pembrolizumab and/or nivolumab with relevant data gathered from clinical charts.
RESULTS: Rheumatic manifestations were encountered in 14 of 400 patients (3.5%)
who had received immunotherapy between January 1st 2013 and April 30th, 2017. The
most common rheumatic manifestation was inflammatory arthritis (85%) for which a
third (4/11) had a clear cut predisposing factor such as a personal or family
history of psoriasis, a prior episode of uveitis or ACPA positivity. Pulmonary
sarcoidosis and biopsy-proven eosinophilic fasciitis were diagnosed in two
additional patients. Treatment with NSAIDS was mostly unsuccessful while steroid
therapy was beneficial in doses >=20 mg/d. Methotrexate enabled steroid tapering
without an excess of side effects or tumor progression in the short follow-up
available. Overall, rheumatic manifestations tended to occur later in the course
of immunotherapy as compared to other iAE. CONCLUSIONS: Our findings underscore
that rheumatic iAE are part of the side effect profile of ICIs and require
heightened awareness as these therapies are becoming the standard of care for
various malignancies. We show that these appear later in the course of iAEs and
respond preferentially to high dose steroids. MTX appears effective as a steroid
sparing agent.
PMID- 29341937
TI - Correction for: Opening the Black Box of Electronic Health: Collecting,
Analyzing, and Interpreting Log Data.
AB - [This corrects the article DOI: .].
PMID- 29341938
TI - Increased serum concentrations of soluble ST2 are associated with pulmonary
complications and mortality in polytraumatized patients.
AB - BACKGROUND: We sought to evaluate the role of soluble ST2 (suppression of
tumorigenicity) serum concentrations in polytraumatized patients and its
potential role as biomarker for pulmonary complications. METHODS: We included
severely injured patients (injury severity score>=16) admitted to our level I
trauma center and analyzed serum samples obtained on the day of admission and on
day 2. Furthermore, patients with isolated thoracic injury and healthy probands
were included and served as control groups. Serum samples were analyzed for
soluble ST2 concentrations with a commercially available ELISA kit. RESULTS: A
total of 130 patients were included in the present study. Five patients with
isolated thoracic injury and eight healthy probands were further included. Serum
analyses revealed significantly elevated concentrations of soluble ST2 in
polytraumatized patients compared to patients suffering from isolated thoracic
trauma and healthy probands. In polytraumatized patients who developed pulmonary
complications (acute respiratory distress syndrome and pneumonia) and in patients
who died, significantly higher serum concentrations of soluble ST2 were found on
day 2 (p<0.001). Serum concentrations of soluble ST2 on day 2 were of prognostic
value to predict pulmonary complications in polytraumatized patients (area under
the curve=0.720, 95% confidence interval=0.623-0.816). Concomitant thoracic
trauma had no further impact on serum concentrations of soluble ST2. CONCLUSIONS:
Serum concentrations of soluble ST2 are upregulated following polytrauma.
Increased concentrations were associated with worse outcome.
PMID- 29341939
TI - The quest for equivalence of test results: the pilgrimage of the Dutch
Calibration 2.000 program for metrological traceability.
PMID- 29341940
TI - Mucocele of the Sphenoid Sinus.
AB - Mucocele of the paranasal sinuses is a rare disease with slow evolution. It is a
benign, encapsulated and destructive formation filled with mucous fluid and
tapistrated with respiratory epithelium. Of all the paranasal sinuses, the
sphenoid sinus is affected in only 1-7% of the cases. We present two cases of
mucocele of the sphenoid sinus involving the posterior ethmoidal cells. We
consider here their clinical presentation, use of neuroimaging in the diagnosis,
surgical care and postoperative results. Both patients presented with a history
of persistent headache and in addition, one of them had a paresis of the right
oculomotor and abducens nerves. A transnasal endoscopic sphenoidectomy was
performed in both patients, in one - with an evacuation of the mucocele and
marsupialization, and in the other - with a balloon dilatation of the natural
foramen of the sinus. Postoperatively, a complete reversal of the symptoms was
observed in both patients. Mucocele of the paranasal sinuses should be considered
as a diagnosis in cases of persistent headache with a primarily retrobulbar
location and eye symptoms. Computed tomography and magnetic resonance imaging can
be used to successfully diagnose the disease. The transnasal endoscopic
sphenoidectomy is the therapeutic method of choice which allows evacuation of the
mucocele, while the marsupialization allows good drainage and prevents
recurrence.
PMID- 29341941
TI - Cauda Equina Syndrome Due to Lumbar Disc Herniation: a Review of Literature.
AB - Cauda equina syndrome (CES) is a rare neurologic condition that is caused by
compression of the cauda equina. Cauda equina consists of spinal nerves L2-L5, S1
S5 and the coccygeal nerve. The compression of these nerve roots can be caused
mainly by lumbar disc herniation (45% of all causes). The diagnosis consists of
two critical points: a) detailed history and physical examination and b) MRI or
CT. The gold standard of the treatment of this syndrome is the surgical approach
in combination with the timing of onset of symptoms. The surgery as an emergency
situation is recommended in the fi rst 48 hours of onset of symptoms. Any delay
in diagnosis and treatment leads to a poor prognosis of CES.
PMID- 29341942
TI - Enteritis-associated Acute Febrile Neutrophilic Dermatosis with Acute
Monoarthritis.
AB - Febrile neutrofilic dermatosis is an uncommon entity with complex
pathophysiology, usually secondary to an infection, a malignancy or an autoimmune
disease. Extracutaneous manifestations of the disease are very rare as well. We
report a patient with histologically confirmed acute febrile neutrophilic
dermatosis caused by viral enteritis that was presented with painful rash along
with acute monoarthritis and treated with oral corticosteroids.
PMID- 29341943
TI - Beneficial Effect of Chronic Treatment with Extracts from Rhodiola Rosea L. and
Curcuma Longa L. on the Immunoreactivity of Animals Subjected to a Chronic Mild
Stress Model.
AB - BACKGROUND: Recent studies have suggested increased levels of pro-inflammatory
cytokines in depression. AIM: The present study aimed to evaluate the effect of
extracts from Rhodiola and Curcuma on immunoreactivity of animals subjected to a
chronic mild stress (CMS) model followed by lipopolysaccharide-induced
inflammation. MATERIALS AND METHODS: Male Wistar rats (n=56) divided in 7 groups
were treated orally with: distilled water 10 ml/kg (control and CMS model
groups); Rhodiola 250 mg/kg; Rhodiola 500 mg/kg; Curcuma 250 mg/kg; Curcuma 500
mg/kg, Rhodiola 250 mg/kg and Curcuma 250 mg/kg. All groups except the control
were stressed daily according to a CMS protocol. Changes in glucose preference,
weight gain and locomotor activity were recorded. In the sixth week the animals
were challenged with LPS and rats' sera were obtained for ELISA evaluation of TNF
alpha and IL-6 levels. RESULTS: The animals from the model group decreased their
weight gain, glucose preference and locomotor activity compared to controls. The
groups exposed to stress and treated with Rhodiola 500 mg/kg, Curcuma 500 mg/kg
and their combination increased their locomotor activity compared to the model
group. High expression of the pro-inflammatory cytokines TNF-alpha and IL-6 were
found in all groups exposed to CMS and challenged by LPS. CONCLUSIONS: The groups
exposed to the stress procedure showed a variety of depression-like behavioral
changes. In addition, ELISA tests showed that CMS is affecting rats' immunity by
increasing the cytokines' levels. These changes could be reversed by
administration of Rhodiola and Curcuma in combination suggesting synergic
interaction regarding their anti-inflammatory and anti-stress effects.
PMID- 29341944
TI - Nuclear Medicine Methods for Evaluation of Abnormal Parathyroid Glands in
Patients with Primary and Secondary Hyperparathyroidism.
AB - Considered rare disease in the past, primary hyperparathyroidism (PHPT) has
dramatically increased in incidence over the past thirty years with the
introduction of routine calcium measurements; it is now approximately 42 per 100
000 persons. By far, the most common lesion found in patients with PHPT is the
solitary parathyroid adenoma, occurring in 85%-90% of patients, while in the rest
10%- 15% primary hyperplasia of the parathyroid glands is present. Currently, the
most widely used surgical approach is minimally invasive parathyroidectomy which
is associated with less post-surgery complications and shorter operation time. To
be successful this procedure needs to rely on a precise preoperative localization
of the abnormal parathyroid glands, hence preoperative parathyroid imaging gained
so large importance. The rationale for locating abnormal parathyroid tissue prior
to surgery is that the glands can be notoriously unpredictable in their location.
There is a general consensus that the best imaging procedure identifying abnormal
parathyroid glands is the preoperative scintigraphy with 99mTc-sestamibi or 99mTc
tetrofosmin. It is characterized with high sensitivity and specificity exceeding
those of ultrasound, CT or MRI. Combining scintigraphy with the other imaging
techniques increases the precision for topic localization.
PMID- 29341945
TI - Lessons about Causes and Management of an Ebola Outbreak.
AB - Ebola virus disease (EVD) is one of the deadliest viral diseases. It is
characterized by a high mortality rate due to the lack of effective and safe
treatments or vaccines and its ability to spread at an unstoppable pace. The West
Africa outbreak ended but the disease may strike again at any time. The latest
epidemic was, by far, the deadliest to date. The most concern was why this
outbreak was so different from the previous ones. We proposed in this review
firstly to summarize the principal causes of its unprecedented spread and
secondly to identify the steps for an effective management approach of a future
Ebola outbreak. Attributes of the affected populations and insufficient control
efforts were the main reasons of its amplification. This was complicated by a
delayed international response. The health crisis was ignored for months until it
got out of control. The management of Ebola presents a multitude of challenges in
terms of preparedness and capacity to face an outbreak. In addition to the need
for adequate health care facilities, ongoing surveillance tools, appropriate
training of health workers and raising population awareness, readiness requires a
large scale and coordinated international intervention to support affected and at
risk nations, to intensify their response activities and to strengthen their
capacities. Constant interventions after the outbreak are still needed to ensure
that vital health and related service institutions in these countries are fully
prepared to respond to an eminent epidemic.
PMID- 29341946
TI - Microemulgel of Voriconazole: an Unfathomable Protection to Counter Fungal
Contagiousness.
AB - BACKGROUND: Fluconazole and ketoconazole both have poor minimum inhibitory
concentration than voriconazole. Voriconazole had serious side effects in oral
and intravenous doses. It has poor water solubility. The objective of the study
was to prepare and optimize microemulgel of voriconazole for topical delivery.
AIM: Formulation, development, and evaluation of voriconazole microemulgel for
topical delivery. METHODS: Oil and emulsifi ers selected were on the basis of
equilibrium solubility study and emulsification property respectively. The pseudo
ternary plot and constrained simplex lattice design were applied for preparation
of microemulsions. Microemulsions were subjected to micelle size, zeta potential,
polydispersity index, and in vitro study. They were optimized by Design-Expert(r)
9.0.3.1 software. Formulation, development, evaluation and optimization of
microemulgel were carried out. Microbial assay of an optimized batch of
microemulgel was performed. RESULTS: Solubility of voriconazole in Parker Neem(r)
oil was 7.51+/-0.14 mg/g. AcrysolTMK-150: PEG-400 in 4:1 ratio had the highest
area for microemulsion. 59.2% AcrysolTMK-150, 14.8% PEG-400, 11% Parker Neem(r)
oil, 15% rose water, and 1% voriconazole as an optimized batch of microemulsion
was selected for preparation of microemulgel. Carbomer 934P found a good gelling
agent in 0-2% w/w concentration. An optimized batch of microemulgel had 0.974
desirability value. An optimized batch of microemulgel and Nizral(r) cream had
37.32+/-0.63% and 26.45+/-0.63% zones of inhibition. CONCLUSION: Topical
antifungal treatment was successfully achieved with voriconazole microemulgel.
PMID- 29341947
TI - Spontaneous Direct Carotid-Cavernous Fistula in an Elderly Patient.
AB - We describe the case of an 83-year-old woman with left-sided ophthalmoplegia. She
had no family history of connective tissue disease. The computed tomography study
found a dilated left cavernous sinus. The conventional cerebral panangiography
confirmed the diagnosis - a direct carotid-cavernous fistula (CCF), with no
evidence of ruptured aneurysm. The woman underwent endovascular treatment with
coiling of the cavernous sinus in combination with application of the Onyx
embolic agent in the fistula. During the first 48 hours after the embolization
the local pain, exophthalmos and conjunctival injection of the left eye were
significantly ameliorated. The pulsatile tinnitus on the left disappeared and the
ptosis of the left eyelid partially recovered. Selective angiography is the best
method for the diagnosis and classification of CCF. Currently, treatment is
possible with low mortality and morbidity rates. The endovascular intervention is
able to completely occlude the fistula and maintain adequate blood fl ow through
the carotid artery.
PMID- 29341948
TI - Biochemical Changes in Experimental Rat Model of Abdominal Compartment Syndrome.
AB - BACKGROUND: Increased intra-abdominal pressure (IAP) causes tissue ischemia,
subsequent hypoxia, and impairment of normal tissue metabolism. Elevation of IAP
above 20 mmHg leads to progression of abdominal compartment syndrome (ACS) that
is associated with organ dysfunction or failure not previously manifested. AIM:
To evaluate the eff ects of diff erent grades and time of exposure to IAP on
biochemical parameters and oxidative stress in organs aff ected by ischemia using
previously developed rat model. RESULTS: Three experimental groups exposed to
diff erent IAP and time frames were tested for liver, kidney, and pancreas injury
by measuring the activities of tissue specifi c enzymes in blood serum. Elevated
activities of aspartate aminotransferase, pancreatic amylase, lipase, and higher
concentrations of D-lactate, urea, and creatinine were found in some of the
experimental groups compared to a control group of animals not subjected to
increased IAP. Increased levels of biomarkers of oxidative stress as well as
decrease in concentration of the major cellular antioxidant glutathione indicated
the presence of oxidative injury as a result of elevated IAP. CONCLUSIONS: The
developed rat model is appropriate to study the mechanism and manifestation of
tissue injury during diff erent grades of elevated IAP but also to test
approaches aimed to attenuate the detrimental eff ects of ACS. This study also
underlines the necessity of using not a single but a set of biochemical
parameters in order to assess the severity of tissue injury during elevated IAP
and progression to ACS.
PMID- 29341949
TI - Impact of Air Pollution and Outdoor Temperature on the Rate of Chronic
Obstructive Pulmonary Disease Exacerbations.
AB - BACKGROUND: Environmental pollution can be one of the main risk factors for acute
exacerbations of chronic obstructive pulmonary disease (COPD). AIM: To study the
relationship between air pollution, outdoor temperature and exacerbations of
COPD. MATERIALS AND METHODS: COPD patients (n=1432) were followed up for one
year. The levels of particulate matter up to 10 MUm (PM10), nitrogen dioxide
(NO2), sulfur dioxide (SO2) and outside temperatures were collected from the
Environmental Agency database. RESULTS: A total of 309 acute COPD exacerbations
(AECOPD) were recorded in the analysis. The daily mean concentrations of PM10
were found to correlate significantly with the daily mean concentrations of NO2
and SO2 (rho 0.34 and rho 0.49, respectively; p=0.0001). The negative
correlations between the daily mean temperature and the daily mean levels of
PM10, NO2 and SO2 were also significant (rho -0.44, rho -0.11, and rho -0.37,
respectively; p=0.0001). The daily number of AECOPD correlated with the mean
levels of PM10 in the previous six days (rho 0.14; p=0.02) and the lower outdoor
temperature (rho -0.2; p=0.001). The negative correlation between the daily
number of AECOPD and the mean daily temperature was stronger in days with levels
of PM10 above 50 MUg/m3 (rho -0.3 p=0.02 vs. rho -0.18 p= 0.01). CONCLUSION:
Lower daily mean temperatures were associated with the levels of air pollutants.
The level of PM10 correlated with the levels of the other air pollutants. The
daily number of AECOPD was found to correlate weakly, but signifi cantly with the
mean level of PM10 in the previous six days.
PMID- 29341950
TI - Clinical Characteristics of Ulceroglandular Tularemia in Two Bulgarian Regions,
2014-2015: a Report of Five Cases.
AB - We present here the first five human cases with tularemia from two regions in
South Bulgaria in which there had been no previous report of the infection. The
cases occurred over a period of 8 months (December 2014 - August 2015). They were
treated at the Department of Infectious Diseases in Stara Zagora University
Hospital, Bulgaria. We present the clinical, epidemiological and laboratory data
for four men and one woman (age range 52 to 73 years). Three men were hunters,
four patients took part in handling, preparing/skinning and cooking the game
animals. One man marked agricultural work and contact with straw stems. After a
mean incubation period of 4.8+/-1.4 days ulcers appeared, followed by local
painful lymphadenitis. All patients presented with liver enlargement and
elevation in acute phase reactants. The etiological diagnosis was made by tube
agglutination test in all cases, PCR positive result was found in one. The
administered antibacterial treatment was a combination of aminoglycosides and 4
quinolones with the outcome being favorable for all patients. The current report
suggests presence of Francisella tularensis in South Bulgaria.
PMID- 29341951
TI - Spermicidal Constituents of Ethanolic Extract of Sacoglottis gabonensis Stem
Bark.
AB - AIM: To isolate the spermicidal constituents of Sacoglottis gabonensis. MATERIALS
AND METHODS: The ethanolic extract with partitioned fractions of Sacoglottis
gabonensis stem bark were subjected to sperm immobilization assay. The most
active EtOAc fraction was further purifi ed by column and Semi-Preparative High
Performance Liquid Chromatography to give compounds which were characterized by
spectroscopic methods (UV, LC/MS, and NMR). The compound(s) was also tested for
sperm immobilization activity. RESULTS: The ethanolic extract showed 100% signifi
cant (p < 0.05) sperm immobilization activity at a concentration of 30 mg/mL at
20 s compared to both negative and positive controls. The most active ethyl
acetate fraction yielded methyl 3,5-dihydroxy-4-methoxybenzoate, eriodictyol and
bergenin. Bergenin had 100% sperm immobilization activity at 20 mg/mL in 60 s
which was signifi cant (p < 0.05) also when compared to the positive and negative
control while methyl 3,5-dihydroxy- 4-methoxybenzoate, eriodictyol were not
active. CONCLUSION: The active spermicidal constituent in Sacoglottis gabonensis
stem bark extract is bergenin. However, methyl 3,5-dihydroxy-4-methoxybenzoate
and eriodictyol showed no activity. This plant is known for its aphrodisiac
action; hence, caution may have to be exercised in its use because of its
spermicidal eff ect.
PMID- 29341952
TI - A Pharmacological Review: Leptadenia reticulata (Wight & Arn.); Jivanti: the Real
Life Giving Plant.
AB - The present review reveals a comprehensive description of various pharmacological
studies carried out on Leptadenia reticulata, a source of several active
compounds, i.e. Leptadenia reticulata plant belonging to family Asclepiadaceae,
it is also known as 'Jivanti', used for the treatment of various ailments in
human civilization as well as used in folk medicine as a remedy in various
reported herbal formulations. The plant has been found to exhibit diverse
pharmacological activities like antibacterial activity, anticancer activity,
lactogenic eff ect, antioxidant activity, anti-implantation activity, anti
asthmatic activity, modulating eff ect, activity of silver nano particles,
hepatoprotective activity, antifungal activity, antidiabetic activity and anti
infl ammatory activity. Traditionally, the plant promotes fi tness and vigor, the
tone of voice, cures eye diseases, fever, and night blindness, cough, maintain
pregnancy and gangrene. In this review, we give the recent scientifi c update on
this plant with therapeutic potential and discuss the methods of carrying out
studies. The present review draws the attention of researchers towards the
potential therapeutic activity of Leptadenia reticulata for their active
constitute.
PMID- 29341953
TI - Lethality among Patients with HIV/AIDS Monitored in the Clinic of Infectious
Diseases in St George University Hospital, Plovdiv, 2010-2014.
AB - BACKGROUND: The introduction of complex antiretroviral therapy has resulted in
signifi cant decrease in the mortality rate of HIV positive patients, but it
still remains unacceptably high, especially in some groups of patients. AIM: To
investigate the death rate in patients with HIV/AIDS, lethality and mortality in
co-infection, and the most common causes and predictors of fatal outcome, focused
on early diagnosis and appropriate therapy. MATERIALS AND METHODS: The study
included 53 deceased patients with HIV/AIDS, monitored at the Clinic of
Infectious Diseases in St George University Hospital, Plovdiv between 01.01.2010
and 31.12.2014. The methods of research included clinical analysis, laboratory
tests, microbiological and serological tests (HCV, HBV, toxoplasmosis), ELISA,
PCR. Statistical analysis was performed by descriptive statistics, the Student's
t-test, the method of Van der Ward, and regression analysis (logistic
regression). RESULTS: During the study period 316 patients with HIV/AIDS were
monitored, 53 of them with lethal outcome. Lethality was 16.7% for the whole
group; in intravenous drug users - 13.8%; in co-infected patients: HIV/M.
tuberculosis - 46%, in HIV/HCV - 17.8%. Lethality and mortality in HIV(+)
patients with co-infections in populations of diff erent age, gender, duration
since starting sART and degree of immunodefi ciency (according to CD4, VL) was
compared with the lethality and mortality in patients with these conditions from
the general population. CONCLUSIONS: Fatal outcome in patients with HIV/AIDS was
most commonly associated with co-infections HIV/M. tuberculosis and HIV/HCV.
Predictors of a fatal outcome are pulmonary tuberculosis, advanced immunodefi
ciency with VL> 500 000 c/MUL and CD4 <100/mm3, absence or non-systemic
antiretroviral therapy.
PMID- 29341954
TI - Carbapenemase Production of Clinical Isolates Acinetobacter baumannii and
Pseudomonas aeruginosa from a Bulgarian University Hospital.
AB - BACKGROUND: Production of Bla OXA-23, OXA-24, OXA-58 and hyperexpression of OXA
51 due to ISAba1 insertion sequence are the leading causes of carbapenem
resistance in Acinetobacter baumannii. The loss of OprD transmembrane protein and
the overexpression of some effl ux pumps are considered to be the main factors
for carbapenem resistance in Pseudomonas aeruginosa whereas metallo-enzymes'
production has a secondary role. AIM: To examine the carbapenem resistance due to
carbapenemase production among clinically signifi cant Gram-negative non
fermenters from St George University hospital, Plovdiv: A. baumannii and P.
aeruginosa. MATERIALS AND METHODS: Forty three A. baumannii and 43 P. aeruginosa
isolates, resistant or with intermediate resistance to imipenem and/or meropenem
were included in the study. They were collected from patients admitted in 14
various hospital wards between 2010 and 2014. Both phenotypic and genetic methods
were used for identifi cation and antimicrobial susceptibility testing. RESULTS:
All A. baumannii demonstrated carbapenemase production determined by a modifi ed
Hodge test whereas P. aeruginosa isolates did not show this phenomenon. OXA-23
genes were determined in 97.7% (42 out of 43) of A. baumannii isolates
indistinguishable from the sequence of the classical ARI-1 gene. OXA-24, OXA-58
and overexpression of OXA-51 were not registered in any of the isolates. All P.
aeruginosa were negative for blaVIM and blaIMP genes. CONCLUSION: The leading
cause of carbapenem resistance in A. baumannii isolates from our hospital is the
carbapenemase production due to the expression of OXA- 23 gene, whereas in P.
aeruginosa - the loss of transmembrane OprD protein and the effl ux pumps'
hyperexpression are suspected to be the main mechanisms.
PMID- 29341955
TI - Emergency medicine residency programs: the changing face of graduate medical
education.
PMID- 29341956
TI - Microbiome associated with denture malodour.
AB - In the past, our inability to cultivate most of the oral microorganisms has
limited our view of this complex ecosystem. In the present study, we utilized
next generation deep sequencing techniques to revisit the microbiome associated
with denture malodour, a growing field with the rise in life expectancy. The
study population comprised 26 full dentures patients (mean age 71 +/- 6.4, 10
males, 16 females) who visited the Tel Aviv University dental geriatric clinic.
Denture malodour was rated organoleptically by a single odour judge, and dentures
scoring 2 and above were considered malodour positive. DNA was extracted from the
swab samples and analysed using next generation deep sequencing 16 s rDNA
technology. Taxa identified could be classified into nine phyla, 29 genera and
117 species. Malodour positive samples showed a higher abundance of the phyla
Firmicutes and Fusobacteria and the genera Leptotrichia, Atopobium, Megasphaera,
Oribacterium and Campylobacter. Microbiome analysis demonstrated higher bacterial
diversity within the malodourous samples and a significant difference in the
microbial profile within the two groups. Taken together these results suggest a
difference between the microbial populations of malodourous and non-malodourous
dentures both in composition and diversity.
PMID- 29341957
TI - Multiple tuning of magnetic biskyrmions using in situ L-TEM in centrosymmetric
MnNiGa alloy.
AB - Magnetic skyrmions are topologically protected spin configurations and have
recently received growingly attention in magnetic materials. The existence of
biskyrmions within a broad temperature range has been identified in our newly
discovered MnNiGa material, promising for potential application in physics and
technological study. Here, the biskyrmion microscopic origination from the spin
configuration evolution of stripe ground state is experimentally identified. The
biskyrmion manipulations based on the influences of the basic microstructures and
external factors such as grain boundary confinement, sample thickness, electric
current, magnetic field and temperature have been systematically studied by using
real-space Lorentz transmission electron microscopy. These multiple tuning
options help to understand the essential properties of MnNiGa and predict a
significant step forward for the realization of skyrmion-based spintronic
devices.
PMID- 29341958
TI - Persistent Asymptomatic Papules on the Chest.
PMID- 29341959
TI - Indeterminate Dendritic Cell Sarcoma in a Patient With Myelodysplastic Syndrome.
PMID- 29341960
TI - Sclerotic Ulcerated Plaque on the Back.
PMID- 29341961
TI - An Unusual Vesiculopustular Eruption: Challenge.
PMID- 29341962
TI - Withdrawal of life-sustaining therapy.
AB - PURPOSE OF REVIEW: The aim of this review is to examine literature relating to
the withdrawal of life-sustaining therapy (WLST). RECENT FINDINGS: Discussions
regarding end-of-life issues in adults and children are not occurring
comprehensively. Discussions relating to the WLST in the pediatric population
varies by institution and may vary by race, age, health insurance, diagnosis, and
severity of illness. Completing advance directives prior to placement of life
sustaining treatments is not consistent practice. With the WLST, differences in
perspectives exist between medical specialties, within one specialty at different
levels of training, and in physicians' ethical and psychological responses to the
WLST. The timing of WLST appears to be influenced by ICU strain and communication
issues. Study outcomes differ regarding the functionally favorable survival of
patients who have had WLST. Universal guidelines for the WLST may not address
individual patient circumstances. SUMMARY: Discussions of end-of-life issues
early in the course of a patient's health care will contribute to the healthcare
team's understanding and respect of the patient's wishes. This article addresses
the withdrawal of left ventricular assist devices; attending physicians and
physicians in training perspectives of WLST; do physicians distinguish between
withholding and WLST; the timing of WLST; guidelines for the process of WLST; and
pediatrics and end-of-life decisions.
PMID- 29341963
TI - Role of the anesthesiologist-intensivist outside the ICU: opportunity to add
value for the hospital or an unnecessary distraction?
AB - PURPOSE OF REVIEW: Given the extremely expensive nature of critical care
medicine, it seems logical that intensivists should play an active role in
designing efficient systems of care. The true value of intensivists, however, is
not well defined. RECENT FINDINGS: Anesthesiologists have taken key roles in
improving patient safety in the operating room. Anesthesia-related mortality
rates have decreased from 20 deaths per 100 000 anesthetics in the early 1980s to
less than one death per 100 000 currently. Anesthesiologist-intensivists remain
rare (less than 5% of certified anesthesiologists), but increasingly play
multiple roles within multidisciplinary teams. This review outlines the roles of
intensivists in performance improvement, perioperative assessment; sedation
services, extracorporeal and mechanical support, and code/rapid response teams.
Critical-care physicians, by definition, work in collaborative multispecialty and
multidisciplinary teams that make it difficult to isolate each team member's
precise contribution to healthcare value. SUMMARY: Anesthesiologist-intensivists
working outside their usual environment provide leadership and clinical guidance
towards improving patient outcomes.
PMID- 29341964
TI - Renal Decapsulation Prevents Intrinsic Renal Compartment Syndrome in Ischemia
Reperfusion-Induced Acute Kidney Injury: A Physiologic Approach.
AB - OBJECTIVES: Acute kidney injury is a serious complication with unacceptably high
mortality that lacks of specific curative treatment. Therapies focusing on the
hydraulic behavior have shown promising results in preventing structural and
functional renal impairment, but the underlying mechanisms remain understudied.
Our goal is to assess the effects of renal decapsulation on regional
hemodynamics, oxygenation, and perfusion in an ischemic acute kidney injury
experimental model. METHODS: In piglets, intra renal pressure, renal tissue
oxygen pressure, and dysoxia markers were measured in an ischemia-reperfusion
group with intact kidney, an ischemia-reperfusion group where the kidney capsule
was removed, and in a sham group. RESULTS: Decapsulated kidneys displayed an
effective reduction of intra renal pressure, an increment of renal tissue oxygen
pressure, and a better performance in the regional delivery, consumption, and
extraction of oxygen after reperfusion, resulting in a marked attenuation of
acute kidney injury progression due to reduced structural damage and improved
renal function. CONCLUSIONS: Our results strongly suggest that renal
decapsulation prevents the onset of an intrinsic renal compartment syndrome after
ischemic acute kidney injury.
PMID- 29341966
TI - Surveying the Literature: Synopsis of Recent Key Publications.
PMID- 29341965
TI - Osmotic Shifts, Cerebral Edema, and Neurologic Deterioration in Severe Hepatic
Encephalopathy.
AB - OBJECTIVES: We sought to determine the effect of acute electrolyte and osmolar
shifts on brain volume and neurologic function in patients with liver failure and
severe hepatic encephalopathy. DESIGN: Retrospective analysis of brain CT scans
and clinical data. SETTING: Tertiary care hospital ICUs. PATIENTS: Patients with
acute or acute-on-chronic liver failure and severe hepatic encephalopathy.
INTERVENTIONS: Clinically indicated CT scans and serum laboratory studies.
MEASUREMENTS AND MAIN RESULTS: Change in intracranial cerebrospinal fluid volume
between sequential CT scans was measured as a biomarker of acute brain volume
change. Corresponding changes in serum osmolality, chemistry measurements, and
Glasgow Coma Scale were determined. Associations with cerebrospinal fluid volume
change and Glasgow Coma Scale change for initial volume change assessments were
identified by Spearman's correlations (rs) and regression models. Consistency of
associations with repeated assessments was evaluated using generalized estimating
equations. Forty patients were included. Median baseline osmolality was elevated
(310 mOsm/Kg [296-321 mOsm/Kg]) whereas sodium was normal (137 mEq/L [134-142
mEq/L]). Median initial osmolality change was 9 mOsm/kg (5-17 mOsm/kg).
Neuroimaging consistent with increased brain volume occurred in 27 initial
assessments (68%). Cerebrospinal fluid volume change was more strongly correlated
with osmolality (r = 0.70; p = 4 * 10) than sodium (r = 0.28; p = 0.08) change.
Osmolality change was independently associated with Glasgow Coma Scale change (p
= 1 * 10) and cerebrospinal fluid volume change (p = 2.7 * 10) in initial
assessments and in generalized estimating equations using all 103 available
assessments. CONCLUSIONS: Acute decline in osmolality was associated with brain
swelling and neurologic deterioration in severe hepatic encephalopathy.
Minimizing osmolality decline may avoid neurologic deterioration.
PMID- 29341968
TI - And Before That.
PMID- 29341967
TI - New Modalities for the Administration of Inhaled Nitric Oxide in Intensive Care
Units After Cardiac Surgery or for Neonatal Indications: A Prospective
Observational Study.
AB - BACKGROUND: Nitric oxide (NO) has a well-known efficacy in pulmonary hypertension
(PH), with wide use for 20 years in many countries. The objective of this study
was to describe the current use of NO in real life and the gap with the
guidelines. METHODS: This is a multicenter, prospective, observational study on
inhaled NO administered through an integrated delivery and monitoring device and
indicated for PH according to the market authorizations. The characteristics of
NO therapy and ventilation modes were observed. Concomitant pulmonary vasodilator
treatments, safety data, and outcome were also collected. Quantitative data are
expressed as median (25th, 75th percentile). RESULTS: Over 1 year, 236 patients
were included from 14 equipped and trained centers: 117 adults and 81 children
with PH associated with cardiac surgery and 38 neonates with persistent PH of the
newborn. Inhaled NO was initiated before intensive care unit (ICU) admission in
57%, 12.7%, and 38.9% with an initial dose of 10 (10, 15) ppm, 20 (18, 20) ppm,
and 17 (11, 20) ppm, and a median duration of administration of 3.9 (1.9, 6.1)
days, 3.8 (1.8, 6.8) days, and 3.1 (1.0, 5.7) days, respectively, for the adult
population, pediatric cardiac group, and newborns. The treatment was performed
using administration synchronized to the mechanical ventilation. The dose was
gradually decreased before withdrawal in 86% of the cases according to the usual
procedure of each center. Adverse events included rebound effect for 3.4% (95%
confidence interval [CI], 0.9%-8.5%) of adults, 1.2% (95% CI, 0.0%-6.7%) of
children, and 2.6% (95% CI, 0.1%-13.8%) of neonates and methemoglobinemia
exceeded 2.5% for 5 of 62 monitored patients. Other pulmonary vasodilators were
associated with NO in 23% of adults, 95% of children, and 23.7% of neonates. ICU
stay was respectively 10 (6, 22) days, 7.5 (5.5, 15) days, and 9 (8, 15) days and
ICU mortality was 22.2%, 6.2%, and 7.9% for adults, children, and neonates,
respectively. CONCLUSIONS: This study confirms the safety of NO therapy in the 3
populations with a low rate of rebound effect. Gradual withdrawal of NO combined
with pulmonary vasodilators are current practices in this population. The use of
last-generation NO devices allowed good compliance with recommendations.
PMID- 29341969
TI - Pursuing Normality: Reflections on Cancer Survivorship Care of Lymphoma
Survivors.
AB - BACKGROUND: The present study explored the reflections on cancer survivorship
care of lymphoma survivors in active treatment. Lymphoma survivors have
survivorship care needs, yet their participation in cancer survivorship care
programs is still reported as low. OBJECTIVE: The aim of this study was to
understand the reflections on cancer survivorship care of lymphoma survivors to
aid the future planning of cancer survivorship care and overcome barriers to
participation. METHODS: Data were generated in a hematological ward during 4
months of ethnographic fieldwork, including participant observation and 46
semistructured interviews with 9 lymphoma survivors. Interpretive description
methodology and social practice theory guided the analytical framework. RESULTS:
"Pursuing normality" was an overall finding and was comprised of 2 overarching
patterns, "future prospects" and "survivorship care perceptions," both implying
an influence on whether to participate in cancer survivorship care programs.
Because of "pursuing normality," 8 of 9 participants opted out of cancer
survivorship care programming due to prospects of "being cured" and perceptions
of cancer survivorship care as "a continuation of the disease." CONCLUSION: The
findings add to our understanding of possible barriers for participation in
cancer survivorship care and outline important aspects to account for in the
practice of health professionals. IMPLICATIONS FOR PRACTICE: The study findings
may guide practice to establish a systematic approach for providing information
to cancer survivors regarding the possible management of their symptoms and of
the content and purpose of cancer survivorship care.
PMID- 29341970
TI - Does the use of indirect calorimetry change outcome in the ICU? Yes it does.
AB - PURPOSE OF REVIEW: To review the recent findings on metabolic monitoring and
possible beneficial effects of an adequate nutrition therapy, based on indirect
calorimetry as the golden standard to predict energy expenditure. RECENT
FINDINGS: in the last decades, major steps are taken in the field of metabolism
and nutrition, evolving from nutrition as a baseline support to a therapeutic
intervention. The aspect of energy expenditure is of cardinal importance, and
technical possibilities have impressively improved: from the first 'calorimetre'
in 1789 to the new generation, clinical applicable indirect calorimeters and the
high accuracy and easy use model reaching high technology readiness level [Oshima
et al. (2017). Clin Nutr 36:651]. Several recent studies provide information on
the technique of metabolic monitoring itself and the positive effects of
implementation of the tool in a high-end nutritional care plan [Oshima et al.
(2017). Clin Nutr 36:651]. The combination of correct energy provision and
protein prescription has shown benefits, and mortality of ICU patients is related
to the amount of energy provided [Zusman et al. (2016). Crit Care 20:367]. The
use of a monitor per se will not change outcome. Optimal dosing of artificial
nutrition can be achieved by the use of a parameter acquired by a measurement
instead of by inaccurate equations. In the era of precision medicine, this
approach has shown positive effects on outcome. Moreover, above all, the concept
of metabolic monitoring of the critically ill is just an issue of common sense.
SUMMARY: Metabolic monitoring by indirect calorimetry is achieving a level in
which it can be implemented in critical care practice. Evidence is available to
prove that by guiding your nutritional therapy by measured values, it will change
outcome of critically ill patients.
PMID- 29341971
TI - Atopy in Patients With Ocular Cicatricial Pemphigoid.
AB - PURPOSE: To evaluate the presence of atopy in patients with ocular cicatricial
pemphigoid (OCP). METHOD: Patient encounters between August 2005 and November
2016 at the Massachusetts Eye Research and Surgery Institute (MERSI) were
searched to identify those with biopsy-proven OCP who had concurrent evidence of
atopy. RESULTS: There were 230 patients with biopsy-proven OCP. Thirty-three of
them were found to have clinical symptoms of atopy (asthma, hay fever, and
eczema) and of these, 23 had evidence of atopy in their conjunctival biopsy
specimens. All patients were administered immunomodulatory therapy for treatment
of their OCP with 20 patients requiring additional antiallergy treatment to
control residual atopic ocular symptoms. Among patients who used antiallergy
medications, 80% showed improvement in residual symptoms. Rituximab and/or
intravenous immunoglobulin is a preferred OCP medication for patients with OCP
with some evidence of atopy. CONCLUSIONS: Clinicians should consider the
coexistence of atopy in patients with OCP, especially in those with persistent
symptoms after initiation of immunomodulatory therapy.
PMID- 29341972
TI - Ocular Surface and Tear Film Characteristics in a Sclerodermatous Chronic Graft
Versus-Host Disease Mouse Model.
AB - PURPOSE: To report the characteristics of the ocular surface in a previously
established sclerodermatous chronic graft-versus-host disease (cGVHD) mouse
model. METHODS: The ocular surface features and tear film parameters of the mouse
model were assessed by histopathology, immunohistochemistry, electron microscopy,
quantitative polymerase chain reaction, and flow cytometry. RESULTS: The mice
exhibited loss of body weight and decreased tear secretion (P < 0.001), mimicking
the clinical features of patients with cGVHD. Ocular examination demonstrated
significant corneal epithelial staining, conjunctival (P < 0.001), and eyelid (P
= 0.015) fibrosis compared with the control mice. The density of both goblet
cells (P = 0.043) and microvilli was lower (P < 0.001), and the microvilli were
shorter (P = 0.007) in the conjunctiva of cGVHD mice than those of the controls.
The immunohistochemical studies demonstrated greater expression of CD45, CD4, and
CD8 cells in the conjunctiva and eyelid tissues compared with the controls (P <
0.05 for all). In addition, reduced Forkhead box P3 (Foxp3)+ cells were found in
both the peripheral blood (P < 0.001) and conjunctiva (P = 0.042) of cGVHD mice
compared with the controls. CONCLUSIONS: The constellation of these findings
suggests that the sclerodermatous cGVHD mouse model well recapitulates ocular
manifestations of cGVHD in humans. This model can be used to study the mechanisms
involved in the pathogenesis and treatment of chronic ocular graft-versus-host
disease.
PMID- 29341973
TI - Detection and Imaging of Lymphatic and Other Vessels in Corneal Neovascular
Complexes.
PMID- 29341974
TI - Feasibility and Effectiveness of Continuing Methadone Maintenance Treatment
During Incarceration Compared With Forced Withdrawal.
AB - BACKGROUND: Methadone maintenance treatment (MMT) is underutilized in
correctional settings, and those receiving MMT in the community often undergo
withdrawal upon incarceration. Federal and state regulations present barriers to
providing methadone in correctional facilities. For this investigation, a
community provider administered methadone to inmates who had been receiving
methadone prior to incarceration. We hypothesized that inmates continued on MMT
would have improved behavior during incarceration and post-release. METHODS: This
open-label quasi-experimental trial (n = 382) compared MMT continuation
throughout incarceration (n = 184) to an administrative control group (ie, forced
withdrawal; n = 198) on disciplinary tickets and other program attendance during
incarceration. Post-release, re-engagement in community-based MMT and 6-month
recidivism outcomes were evaluated. RESULTS: Inmates in the MMT continuation
group versus controls were less likely to receive disciplinary tickets (odds
ratio [OR] = 0.32) but no more likely to attend other programs while
incarcerated. MMT continuation increased engagement with a community MMT provider
within 1 day of release (OR = 32.04), and 40.6% of MMT participants re-engaged
within the first 30 days (vs 10.1% of controls). Overall, re-engagement in MMT
was not associated with recidivism. However, among a subset of inmates who
received MMT post-incarceration from the jail MMT provider (n = 69), re
engagement with that provider was associated with reduced risk of arrest, new
charges, and re-incarceration compared with those who did not re-engage.
CONCLUSIONS: Results support interventions that facilitate continuity of MMT
during and after incarceration. Engagement of a community provider is feasible
and can improve access to methadone in correctional facilities.
PMID- 29341975
TI - Validation of a Simplified Implant-Retained Cantilever Fixed Prosthesis.
AB - PURPOSE: To evaluate the stress and strain generated in a fixed four-element
prosthesis under the application of axial and nonaxial loads using a simplified
implant-supported fixed prosthesis model. MATERIALS AND METHODS: A 3-dimensional
model was constructed containing 3 implants with a conventional anatomical
prosthesis (G1). The second model with the same implant system received the
simplified prosthesis (G2). A load of 300 N was applied at an axial point and a
nonaxial point through finite element analysis software. RESULTS: The G2 group
showed different values of stress concentration in the prosthesis, fixation
screw, retention screw, and abutments when compared with G1. Within a limit of
10% degrees of acceptability, the stress on the implants and the bone strain were
enclosed for both models of prostheses. CONCLUSION: The simplified fixed
prosthesis evaluated presents biomechanical behavior similar to an anatomical
prosthesis in the implants and in the surrounding bone structure.
PMID- 29341976
TI - Cone-Beam CT Assessment of the Position of the Medial Lingual Foramen for Dental
Implant Placement in the Anterior Symphysis.
AB - OBJECTIVES: To determine the position of the mandibular medial lingual foramen
with cone-beam CT (CBCT) 3D imaging modalities when implants are to be placed in
the anterior symphysis of the mandible. MATERIALS AND METHODS: A total of 111
CBCTs were considered acceptable and analyzed. The variables measured were as
follows: (1) length of the outlet duct; (2) distance from the canal to the buccal
cortex; (3) distance from the canal to the inferior cortex; (4) distance from the
canal to the lingual cortex; (5) distance from the canal to the alveoli of the
nearest tooth in dentate patients and distance from the canal to the marginal
crest in edentulous patients; (6) angle of the duct to the horizontal Frankfurt
plane; (7) diameter of the exit orifice; and (8) output level of the socket in
relation to the teeth and the presence of bifurcations. RESULTS: A single canal
was observed in 64% of patients; 2 canals were observed in 33% of patients; and a
triple foramen was observed in 3% of patients. Women showed slightly lower values
than men for each of the analyzed variables, with statistically significant
differences in the length of the canal in edentulous (P = 0.029) and dentate
patients (P = 0.027). CONCLUSION: The medial lingual foramen should be considered
while performing presurgical planning. Careful attention is needed while setting
the placement position of the dental implant to decrease the risk of
complications.
PMID- 29341977
TI - Elemental Composition at Silicone Hydrogel Contact Lens Surfaces.
AB - OBJECTIVES: The outermost surface composition of 11 silicone hydrogel (SiHy)
lenses was measured using X-ray photoelectron spectroscopy (XPS) to understand
differences in wettability and potential interactions within an ocular
environment. The SiHy lenses tested included balafilcon A, lotrafilcon A,
lotrafilcon B, senofilcon A, comfilcon A, and somofilcon A reusable 2-week or
monthly replacement lenses and delefilcon A, samfilcon A, narafilcon A,
stenfilcon A, and somofilcon A daily disposable lenses. METHODS: All lenses were
soaked for 24 hr in phosphate-buffered saline to remove all packaging solution
and dried under vacuum overnight before analysis. X-ray photoelectron
spectroscopy measurements were performed at 2 take-off angles, 55 degrees and 75
degrees , to evaluate changes in elemental composition as a function of depth
from the surface. RESULTS: Detailed analysis of the XPS data revealed distinct
differences in the chemical makeup of the different lens types. For all lenses,
carbon, oxygen, and nitrogen were observed in varying quantities. In addition,
fluorine was detected at the outermost surface region of comfilcon A (3.4%) and
lotrafilcon A and B (<0.5%). The silicon content of the near-surface region
analyzed varied among lens types, ranging from a low of 1.6% (lotrafilcon B) to a
high of 16.5% (comfilcon A). In most instances, silicon enrichment at the
outermost surface was observed, resulting from differences in lens formulation
and design. CONCLUSIONS: Lenses differed most in their surface silicon
concentration, with lotrafilcon B and delefilcon A exhibiting the lowest silicon
contents and comfilcon A lens exhibiting the highest. Silicon has hydrophobic
properties, which, when found at the surface, may influence the wettability of
the contact lenses and their interaction with the tear film and ocular tissues.
Higher surface silicon contents have been previously correlated with adverse
effects, such as enhanced lipid uptake, thus underscoring the importance of
monitoring their presence.
PMID- 29341978
TI - Assessment of Clinical Trials for Devices Intended to Control Myopia Progression
in Children.
AB - The increased prevalence of myopia in the United States and other regions of the
world, and the sight-threatening problems associated with higher levels of myopia
have led to great interest in research designed to reduce these rates. As most of
the progression of myopia occurs in childhood, these investigations have been
directed toward slowing the progression of myopia in children. Treatments
described to potentially slow the progression of myopia have included
pharmacological interventions, multifocal spectacles, and multifocal correction
created by contact lenses. Although some contact lens clinical trials have
demonstrated promising results in slowing the progression of myopia, many of
these studies have significant limitations, including only short follow-up times,
limited randomization, and incomplete masking. Such limitations have underscored
the need to develop a more robust clinical study design, so that future studies
can demonstrate whether contact lenses, as well as other medical devices, can be
used in a safe and effective manner to control myopia progression. We review
previous key studies and discuss study design and regulatory issues relevant to
future clinical trials.
PMID- 29341979
TI - Wilson's Disease in Children: A Position Paper by the Hepatology Committee of the
European Society for Paediatric Gastroenterology, Hepatology and Nutrition.
AB - BACKGROUND: Clinical presentations of Wilson's disease (WD) in childhood ranges
from asymptomatic liver disease to cirrhosis or acute liver failure, whereas
neurological and psychiatric symptoms are rare. The basic diagnostic approach
includes serum ceruloplasmin and 24-hour urinary copper excretion. Final
diagnosis of WD can be established using a diagnostic scoring system based on
symptoms, biochemical tests assessing copper metabolism, and molecular analysis
of mutations in the ATP7B gene. Pharmacological treatment is life-long and aims
at removal of copper excess by chelating agents as D-penicillamine, trientine, or
inhibition of intestinal copper absorption with zinc salts. Acute liver failure
often requires liver transplantation. This publication aims to provide
recommendations for diagnosis, treatment, and follow-up of WD in children.
METHODS: Questions addressing the diagnosis, treatment, and follow-up of WD in
children were formulated by a core group of ESPGHAN members. A systematic
literature search on WD using MEDLINE, EMBASE, Cochrane Database from 1990 to
2016 was performed focusing on prospective and retrospective studies in children.
Quality of evidence was assessed according to the GRADE system. Expert opinion
supported recommendations where the evidence was regarded as weak. The ESPGHAN
core group and ESPGHAN Hepatology Committee members voted on each recommendation,
using the nominal voting technique.
PMID- 29341980
TI - How Much Free Sugars Intake Should Be Recommended for Children Younger Than 2
Years Old?
PMID- 29341981
TI - Response to Letter: How Much Free Sugars Intake Should Be Recommended for
Children Younger Than Two Years Old?
PMID- 29341982
TI - Extensive Necrotic Skin Lesions Due to Post-varicella Protein S Deficiency.
AB - Postvaricella protein S deficiency is a rare and severe disease. We report a case
of extensive necrotic skin lesions of acute onset 7 days after varicella in a 4
year-old girl. Protein S antigen and activity were <10%, and antiprotein S
antibodies were detected. She was treated with anticoagulation, plasmapheresis
and fresh frozen plasma. She survived but required leg amputation.
PMID- 29341983
TI - Diarrheagenic Escherichia coli and Acute Gastroenteritis in Children in Davidson
County, Tennessee, United States: A Case-control Study.
AB - BACKGROUND: Diarrheagenic Escherichia coli (DEC) is an important cause of acute
gastroenteritis in children; however, there is limited information available on
the epidemiology, phylogenetics, serotyping and antibiotic susceptibility of DEC
in children in the United States. The aim of this study was to determine the
molecular epidemiology of DEC among children with and without acute
gastroenteritis in Davidson County, Tennessee. METHODS: This prospective,
frequency matched, case-control study recruited subjects 15 days to 17 years of
age and detected DEC with polymerase chain reaction from stool samples.
Additional testing was done to define phylogenetics and antibiotics resistance.
RESULTS: Among 1267 participants, 857 cases and 410 controls, 5.5% were positive
for at least one subtype of DEC. Enteroaggregative E. coli [n = 32 (45%)] was the
most common subtype followed by enteropathogenic E. coli (EPEC) [n = 30 (43%)],
Shiga toxin-producing E. coli [n = 4 (6%)] and diffusely adherent E. coli [n = 4
(6%)]. No significant difference in prevalence of DEC was found between cases
(5%) and controls (7%) [odds ratio: 0.66 (95% confidence interval: 0.4-1.07)],
and results were similar when data were stratified by subtypes and adjusted for
age, sex, race and ethnicity. Substantial diversity was found among DEC isolates
in terms of phylotypes and serotypes, and a large proportion was resistant to, at
least, one antibiotic. CONCLUSIONS: Enteroaggregative E. coli and
enteropathogenic E. coli were frequently found in both cases and controls in this
study population. DNA-based methods for detection of these subtypes need further
investigation to help differentiate between pathogenic and colonizing strains.
PMID- 29341984
TI - Effect of Age at Vaccination on Rotavirus Vaccine Effectiveness in Bolivian
Infants.
AB - BACKGROUND: Rotavirus vaccines are less effective in developing countries versus
developed countries. One hypothesis for this difference in performance is that
higher levels of maternal antibodies in developing countries may interfere with
vaccine response, suggesting that delayed dosing could be beneficial. The present
analysis aims to assess whether rotavirus vaccine effectiveness (VE) varies by
age at vaccination during routine use in Bolivia. METHODS: Data were merged from
2 postlicensure evaluations of monovalent rotavirus vaccine (RV1) in Bolivia,
where 2 doses of RV1 are recommended at 2 and 4 months of age. For each dose,
children were classified as receiving each dose "early," "on-time" or "late."
Stratified unconditional logistic regression models were used to estimate VE,
using unvaccinated children as the referent. VE was calculated as (1 - odds
ratio) * 100%. Models were adjusted for hospital, age and time since RV1
introduction (via including terms for month and year of birth). RESULTS: VE for 2
doses of RV1 tended to be higher in infants receiving the first dose early (VE,
92%; 95% confidence interval: 70%-98%), when compared with infants receiving
their first dose on-time [72% (62%-81%)] or late [68% (51%-79%)]. Estimates of VE
were not substantially different when comparing children by age at second dose
[early: VE, 76% (50%-89%); on-time: VE, 70% (50%-89%); late: VE, 75% (60%, 84%)],
including all children. CONCLUSIONS: Our results indicate that early
administration may improve VE and support the current World Health Organization
recommendations for the RV1 schedule.
PMID- 29341985
TI - Dexmedetomidine as Single Continuous Sedative During Noninvasive Ventilation:
Typical Usage, Hemodynamic Effects, and Withdrawal.
AB - OBJECTIVES: Dexmedetomidine use in pediatric critical care is increasing. Its
prolonged effects as a single continuous agent for sedation are not well
described. The aim of the current study was to describe prolonged dexmedetomidine
therapy without other continuous sedation, specifically the hemodynamic effects,
discontinuation strategies, and risk factors for withdrawal. DESIGN:
Retrospective chart review. SETTING: Large, single-center, quaternary care
pediatric academic institution. PATIENTS: Data from 382 children, less than 18
years old admitted to the PICU who received dexmedetomidine for more than 24
hours without other infusions for sedation during noninvasive positive pressure
ventilation. INTERVENTIONS: Usual care practices for dexmedetomidine use were
described. Discontinuation strategies were categorized as abrupt discontinuation,
wean from dexmedetomidine infusion, and transition to enteral clonidine.
MEASUREMENTS AND MAIN RESULTS: Median peak and cumulative doses with
interquartile range were 1 ug/kg/hr (0.6-1.2 ug/kg/hr) and 30 ug/kg (20-50
ug/kg), respectively, and median duration was 45 hours (34-66 hr). Four hours
after reaching peak dose, we observed a decrease in heart rate (p < 0.01) with
28% prevalence of bradycardia and an increase in systolic blood pressure (p <
0.01) with 33% prevalence of hypertension and 2% hypotension. During the
escalation phase, the prevalence of bradycardia and hypotension were 75% and a
30%, respectively. Three-hundred thirty-six patients (88%) had abrupt
discontinuation, 37 (10%) were weaned, and nine (2%) were transitioned to
clonidine. Nineteen patients (5%) experienced withdrawal. Univariate risk of
withdrawal was most associated with duration: odds ratio equal to 1.5 (1.3-1.7)
for each 12-hour period (p < 0.01). By multivariate analysis including age,
discontinuation group, dexmedetomidine cumulative dose, and peak dose, only
cumulative dose remained significant with an odds ratio equal to 1.3 (1.1-1.5)
for each 10 MUg/kg (p < 0.01). CONCLUSIONS: Dexmedetomidine use for noninvasive
positive pressure ventilation sedation in pediatric critical care has predictable
hemodynamic effects including bradycardia and hypertension. Although withdrawal
was associated with higher cumulative dose, these symptoms were effectively
managed with short-term enteral clonidine.
PMID- 29341987
TI - BSN in 10: It's the law!
PMID- 29341986
TI - Pulmonary Dead Space Fraction and Extubation Success in Children After Cardiac
Surgery.
AB - OBJECTIVES: 1) Determine the correlation between pulmonary dead space fraction
and extubation success in postoperative pediatric cardiac patients; and 2)
document the natural history of pulmonary dead space fractions, dynamic
compliance, and airway resistance during the first 72 hours postoperatively in
postoperative pediatric cardiac patients. DESIGN: A retrospective chart review.
SETTING: Cardiac ICU in a quaternary care free-standing children's hospital.
PATIENTS: Twenty-nine with balanced single ventricle physiology, 61 with two
ventricle physiology. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We
collected data for all pediatric patients undergoing congenital cardiac surgery
over a 14-month period during the first 72 hours postoperatively as well as prior
to extubation. Overall, patients with successful extubations had lower
preextubation dead space fractions and shorter lengths of stay. Single ventricle
patients had higher initial postoperative and preextubation dead space fractions.
Two-ventricle physiology patients had higher extubation failure rates if the
preextubation dead space fraction was greater than 0.5, whereas single ventricle
patients had similar extubation failure rates whether preextubation dead space
fractions were less than or equal to 0.5 or greater than 0.5. Additionally,
increasing initial dead space fraction values predicted prolonged mechanical
ventilation times. Airway resistance and dynamic compliance were similar between
those with successful extubations and those who failed. CONCLUSIONS: Initial
postoperative dead space fraction correlates with the length of mechanical
ventilation in two ventricle patients but not in single ventricle patients. Lower
preextubation dead space fractions are a strong predictor of successful
extubation in two ventricle patients after cardiac surgery, but may not be as
useful in single ventricle patients.
PMID- 29341989
TI - A private case of allergic contact dermatitis.
PMID- 29341988
TI - Utilizing advance care planning codes.
PMID- 29341990
TI - Non-fasting versus fasting cholesterol measurement.
AB - Fasting for cholesterol measurement has long been the accepted convention. Recent
research expounded in clinical guidelines indicates that nonfasting cholesterol
measurements predict outcomes at least as well as fasting cholesterol
measurements. In most-but not all-clinical scenarios, fasting is not necessary.
This article provides clinical recommendations based on the literature.
PMID- 29341991
TI - Autism spectrum disorder in primary care.
PMID- 29341992
TI - Periodontal disease in children with type 2 diabetes mellitus.
PMID- 29341993
TI - Examining changes to statewide NP practice in Connecticut.
AB - In 2014, Connecticut legislators eliminated the need for advanced practice
registered nurses with 2,000 practice hours to obtain collaborative practice
agreements with physicians. This study examined resulting practice changes,
barriers, and suggestions for improved implementation of independent practice.
Thirteen NPs participated in focus groups to share their experiences and
recommendations.
PMID- 29341994
TI - Understanding tuberculosis in an era of global travel.
AB - With the resurgence of tuberculosis (TB), it is imperative that healthcare
providers have the necessary skills to manage the specialized issues of
prevention, recognition, and treatment of TB. The case study in this article
illustrates these skills for NPs and other advanced practice providers.
PMID- 29341996
TI - Retinal Arterio-Arterial Collaterals in Susac Syndrome.
AB - BACKGROUND: The ophthalmic findings of Susac syndrome (SS) consist of visual
field defects related to branch retinal artery occlusion (BRAO), and fluorescein
angiography (FA) reveals a unique staining pattern. To date, retinal arterial
collateral development has been described only in a single patient. Given that
the immunopathological process in SS induces retinal ischemia, it is conceivable
that abnormal blood vessel development may occur in affected individuals.
METHODS: This is a retrospective observational study. The medical records
including fundus photography and FA of all patients with SS were reviewed, and
those with any type of retinal arterial collateral were identified. RESULTS: A
total of 11 patients were identified with retinal collaterals. Five were men. Age
ranged from 20 to 50 years. Ten patients had arterio-arterial (A-A) collaterals
and 1 had arterio-venous (A-V) collaterals, and all had collaterals remote from
the optic disc. No collaterals were present at onset of illness and the first
developed at 9 months. CONCLUSIONS: The literature reveals scant evidence for the
association between BRAO and retinal arterial collaterals. Our findings indicate
that retinal arterial collaterals in SS are usually A-A and not A-V and may be
more common in this disorder than previously believed. Collaterals do not develop
early in the disease, and there may be a predilection toward development in men.
The chronic inflammatory state of SS may be the stimulus for the development of
these arterial collaterals.
PMID- 29341997
TI - Literature Commentary.
AB - In this issue of Journal of Neuro-Ophthalmology, M. Tariq Bhatti, MD and Mark L.
Moster, MD will discuss the following 6 articles.
PMID- 29341998
TI - Learning From Pediatrics to Secure Medical Education for the Future.
PMID- 29341999
TI - Unlocking the Closet Door: Recurrent Identity Disclosure Experiences Among LGBTQ
Students.
PMID- 29342000
TI - From Subsistence to Sustenance in Physician-Scientist Training.
PMID- 29342001
TI - Beyond USMLE Step 1.
PMID- 29342002
TI - Finding Focus: Recruiting and Supporting Underrepresented Minority Trainees
Starts With Faculty.
PMID- 29342003
TI - How to Maximize Happiness, Stability, and Success Among Medical School
Applicants.
PMID- 29342004
TI - The Privilege of Patient Care: Often Experienced, Rarely Discussed.
PMID- 29342005
TI - From Theoretical Physics to Atomic Bombs: Learning to Value Medical Epistemology.
PMID- 29342006
TI - On Transitions in Training: Boost Bioethics Education.
PMID- 29342007
TI - Learning to Teach.
PMID- 29342008
TI - The R2C2 Model in Residency Education: How Does It Foster Coaching and Promote
Feedback Use?
AB - PURPOSE: The authors previously developed and tested a reflective model for
facilitating performance feedback for practice improvement, the R2C2 model. It
consists of four phases: relationship building, exploring reactions, exploring
content, and coaching. This research studied the use and effectiveness of the
model across different residency programs and the factors that influenced its
effectiveness and use. METHOD: From July 2014-October 2016, case study
methodology was used to study R2C2 model use and the influence of context on use
within and across five cases. Five residency programs (family medicine,
psychiatry, internal medicine, surgery, and anesthesia) from three countries
(Canada, the United States, and the Netherlands) were recruited. Data collection
included audiotaped site assessment interviews, feedback sessions, and debriefing
interviews with residents and supervisors, and completed learning change plans
(LCPs). Content, thematic, template, and cross-case analysis were conducted.
RESULTS: An average of nine resident-supervisor dyads per site were recruited.
The R2C2 feedback model, used with an LCP, was reported to be effective in
engaging residents in a reflective, goal-oriented discussion about performance
data, supporting coaching, and enabling collaborative development of a change
plan. Use varied across cases, influenced by six general factors: supervisor
characteristics, resident characteristics, qualities of the resident-supervisor
relationship, assessment approaches, program culture and context, and supports
provided by the authors. CONCLUSIONS: The R2C2 model was reported to be effective
in fostering a productive, reflective feedback conversation focused on resident
development and in facilitating collaborative development of a change plan.
Factors contributing to successful use were identified.
PMID- 29342009
TI - How Academic Health Systems Can Achieve Population Health in Vulnerable
Populations Through Value-Based Care: The Critical Importance of Establishing
Trusted Agency.
AB - Improving population health may require health systems to proactively engage
patient populations as partners in the implementation of healthy behaviors as a
shared value using strategies that incentivize healthy outcomes for the
population as a whole. The current reactive health care model, which focuses on
restoring the health of individuals after it has been lost, will not achieve the
goal of improved population health. To achieve this goal, health systems must
proactively engage in partnerships with the populations they serve. Health
systems will need the help of community entities and individuals who have the
trust of the population being served and are willing to act on behalf of the
health system if they are to achieve this effective working partnership. The need
for these trusted agents is particularly pertinent for vulnerable and
historically underserved segments of the population. In this Invited Commentary,
the authors discuss ways by which health systems might identify, engage, and
leverage trusted agents to improve the health of the population through value
based care.
PMID- 29342010
TI - The ever-expanding saga of the proprotein convertases and their roles in body
homeostasis: emphasis on novel proprotein convertase subtilisin kexin number 9
functions and regulation.
AB - PURPOSE OF REVIEW: The nine members of the proprotein convertase family play
major physiological roles during development and in the adult, and their
dysregulation leads to various diseases. The primary objective of this article is
to review recent findings on the clinical importance of some of these convertases
concentrating mostly on PCSK9, the ninth member of the convertase family. This
includes the transcriptional and translational regulation of PCSK9, its ability
to enhance the degradation of LDL receptor (LDLR), and the implication of PCSK9
in inflammation and sepsis. RECENT FINDINGS: PCSK9 levels are upregulated by E2F1
and reduced by specific miRNAs and by Annexin A2 that bind the 3' end of its
mRNA. The implication of the LDLR in the clearance of pathogenic bacterial debris
in mice and human puts in perspective a new role for PCSK9 in the regulation of
sepsis. The specific implication of the LDLR in the clearance of Lp(a) is now
confirmed by multiple studies of PCSK9 inhibition in human cohorts. SUMMARY:
Emerging data suggest that PCSK9 can be regulated at the transcriptional and
translational levels by specific factors and miRNAs. The identification of a
novel pocket in the catalytic domain of PCSK9 represents a harbinger for a new
class of small inhibitor drugs. The implication of the LDLR in reducing the
effects of bacterially induced sepsis has been supported by both human and mouse
data. Outcome studies confirmed the clinical importance of reducing PCSK9 levels.
The present review puts in perspective new developments in the PCSK9 biology and
its regulation of the LDLR. VIDEO ABSTRACT: http://links.lww.com/COL/A17.
PMID- 29342011
TI - Utility of Time and Frequency Domain Parameters of Heart Rate Variability in the
Context of Autonomic Disorders Characterized by Orthostatic Dysfunction.
AB - PURPOSE: The clinical significance of heart rate variability in the context of
autonomic dysfunction continues to be a matter of debate. A consensus is lacking
on the best heart rate variability measures for clinical purposes. Therefore, the
purpose of this study was to investigate the utility of heart rate variability
parameters in healthy versus autonomic dysfunction. METHODS: Healthy young (n =
134), healthy older (n = 32), and patients with mild (postural tachycardia
syndrome; n = 25) and severe (neurogenic orthostatic hypotension; n = 34)
autonomic dysfunction were included. Time and frequency parameters during
baseline, head-up tilt (HUT), and heart rate response to deep breathing (HRDB)
were compared. RESULTS: Cardiovagal time parameters were significantly reduced
during HUT in healthy young and postural tachycardia syndrome (P < 0.001).
Healthy young had significantly higher time parameters during baseline, HUT, and
HRDB (P < 0.01). This was reflected by a significantly lower resting heart rate
(HR) (61.4 +/- 9.0 bpm vs. 76.8 +/- 13.6 bpm; P < 0.001) and a smaller
[INCREMENT]HR during HUT (32.8 +/- 10.5 bpm vs. 44.4 +/- 13.3 bpm; P < 0.001).
Time parameters increased in young and postural tachycardia syndrome during HRDB,
which was characterized by a nonsignificant difference in [INCREMENT]HR between
both groups. Time parameters were significantly higher in healthy old versus
neurogenic orthostatic hypotension at rest and during HRDB (P < 0.05). During
HUT, only the SD of all normal RR intervals remained significantly higher. Heart
rate changes corroborated these findings. Resting HR was significantly lower in
healthy older (62.6 +/- 11.0 bpm vs. 70.7 +/- 12.4 bpm), and [INCREMENT]HR during
HRDB was significantly higher (15.9 +/- 9.2 bpm vs. 3.9 +/- 4.2 bpm; P < 0.001).
During HUT, [INCREMENT]HR showed no significant differences. CONCLUSIONS: Time
domain parameters of heart rate variability have a greater utility than frequency
parameters in clinical autonomic disorders.
PMID- 29342013
TI - Development of Minimally Invasive Surgery at Johns Hopkins.
PMID- 29342012
TI - DIFFUSE CHORIORETINOPATHY WITHOUT SEROUS DETACHMENT ASSOCIATED WITH CARDIAC
TRANSPLANTATION.
AB - PURPOSE: To analyze an unusual case of widespread chorioretinopathy after cardiac
transplantation for its potential etiology and clinical significance. METHODS:
Clinical examinations included widefield and macular color and fundus
autofluorescence photography, spectral domain optical coherence tomography,
fluorescein angiography and indocyanine green angiography, full-field
electroretinography, and Goldmann visual fields. PATIENT: A 44-year-old Hispanic
woman was referred to rule out retinitis pigmentosa. Medical history revealed
cardiac transplantation 6 months previously for idiopathic cardiomyopathy.
RESULTS: Visual acuity was 20/20 in both eyes. The fundi showed widespread gray
mottling and little pigmentation, but fundus autofluorescence revealed black
speckling broadly across the fundus, and geographic retinal pigment epithelium
loss in the nasal midperiphery of the left eye. Spectral domain optical coherence
tomography showed normal inner retina, and surprising preservation of outer
nuclear layer, but the ellipsoid zone line was fragmented, and the
interdigitation zone line was replaced with irregular debris. Retinal pigment
epithelium was very thin with occasional excrescences. Electroretinography showed
mild loss of both rods and cones, with mild flicker peak delay only in the left
eye. Fluorescein angiography showed no leakage, but a reticular pigment pattern
in the macula. Indocyanine green angiography showed irregular arteriolar
remodeling, and few large arteries. DISCUSSION AND CONCLUSION: Serous retinopathy
is well known after organ transplantations, but this patient had retinal pigment
epithelium and retinal damage well into the periphery and no leakage. Retinal
dystrophy was deemed unlikely given the relatively good electroretinography. The
indocyanine green vascular changes raise the possibility of a transient choroidal
ischemic event during or shortly after cardiac surgery. The event altered retinal
pigment epithelium diffusely, but allowed for enough regeneration to sustain
retinal function. Diffuse transplant chorioretinopathy may be discovered if
postcardiac transplant patients get peripheral retinal examinations.
PMID- 29342015
TI - Post-treatment/Pre-operative PET Response Is Not an Independent Predictor of
Outcomes for Patients With Gastric and GEJ Adenocarcinoma.
PMID- 29342014
TI - Patterns and Predictors of Return to Work After Major Trauma: A Prospective,
Population-based Registry Study.
AB - OBJECTIVE: To characterize patterns of engagement in work during the 4-year
period after major traumatic injury, and to identify factors associated with
those patterns. BACKGROUND: Employment is an important marker of functional
recovery from injury. There are few population-based studies of long-term
employment outcomes, and limited data on the patterns of return to work (RTW)
after injury. METHODS: A population-based, prospective cohort study using the
Victorian State Trauma Registry. A total of 1086 working age individuals, in paid
employment or full-time education before injury, were followed-up through
telephone interview at 6, 12, 24, 36, and 48 months post-injury. Responses to RTW
questions were used to define 4 discrete patterns: early and sustained; delayed;
failed; no RTW. Predictors of RTW patterns were assessed using multivariate
multinomial logistic regression. RESULTS: Slightly more than half of respondents
(51.6%) recorded early sustained RTW. A further 15.5% had delayed and 13.3%
failed RTW. One in 5 (19.7%) did not RTW. Compared with early sustained RTW,
predictors of delayed and no RTW included being in a manual occupation and injury
in a motor vehicle accident. Older age and receiving compensation predicted both
failed and no RTW patterns. Preinjury disability was an additional predictor of
failed RTW. Presence of comorbidity was an additional predictor of no RTW.
CONCLUSIONS: A range of personal, occupational, injury, health, and compensation
system factors influence RTW patterns after serious injury. Early identification
of people at risk for delayed, failed, or no RTW is needed so that targeted
interventions can be delivered.
PMID- 29342016
TI - Unresectable Colorectal Liver Metastases: When Definitions Matter to
Appropriately Assess Extreme Liver Resection Techniques.
PMID- 29342017
TI - Response: "Unresectable Colorectal Liver Metastases: When Definitions Matter to
Appropriately Assess Extreme Liver Resection Techniques".
PMID- 29342018
TI - Mini- or Less-open Sublay Operation (MILOS): A New Minimally Invasive Technique
for the Extraperitoneal Mesh Repair of Incisional Hernias.
AB - OBJECTIVE: Improvement of ventral hernia repair. BACKGROUND: Despite the use of
mesh and other recent improvements, the currently popular techniques of ventral
hernia repair have specific disadvantages and risks. METHODS: We developed the
endoscopically assisted mini- or less-open sublay (MILOS) concept. The operation
is performed transhernially via a small incision with light-holding laparoscopic
instruments either under direct, or endoscopic visualization. An endoscopic light
tube was developed to facilitate this approach (EndotorchTM Wolf Company). Each
MILOS operation can be converted to standard total extraperitoneal gas endoscopy
once an extraperitoneal space of at least 8 cm has been created. All MILOS
operations were prospectively documented in the German Hernia registry with 1
year questionnaire follow-up. Propensity score matching of incisional hernia
operations comparing the results of the MILOS operation with the laparoscopic
intraperitoneal onlay mesh operation (IPOM) and open sublay repair from other
German Hernia registry institutions was performed. RESULTS: Six hundred fifteen
MILOS incisional hernia operations were included. Compared with laparoscopic IPOM
incisional hernia operation, the MILOS repair is associated with significantly a
fewer postoperative surgical complications (P < 0.001) general complications (P <
0.004), recurrences (P < 0.001), and less chronic pain (P < 0.001). Matched pair
analysis with open sublay repair revealed significantly a fewer postoperative
complications (P < 0.001), reoperations (P < 0.001), infections (P = 0.007),
general complications (P < 0.001), recurrences (P = 0.017), and less chronic pain
(P < 0.001). CONCLUSIONS: The MILOS technique allows minimally invasive
transhernial repair of incisional hernias using large retromuscular/preperitoneal
meshes with low morbidity. The technique combines the advantages of open sublay
and the laparoscopic IPOM repair.ClinicalTrials.gov Identifier NCT03133000.
PMID- 29342019
TI - Hot Spotting as a Strategy to Identify High-Cost Surgical Populations.
AB - OBJECTIVE: The aim of this study was to determine the feasibility of "hot
spotting" in elective surgical populations. BACKGROUND: Prospective
identification of high-cost patients, known as "hot spotting," is well developed
in medical populations, but has not been performed in surgical populations.
Population-based management of surgical expenditures requires identification of
high-cost surgical patients to allow for effective implementation of cost-saving
strategies. METHODS: Using 100% Medicare claims data for 2010 to 2013, we
identified patients aged 65 to 99 years undergoing elective surgical procedures.
We calculated price-standardized Medicare payments for the surgical episode from
the index admission through 30 days after discharge. Patient-level factors
associated with payments were analyzed by multivariable linear regression.
RESULTS: Medicare patients in the highest decile of spending accounted for a
disproportionate share of aggregate costs: 30% in Colectomy (COL), 22% in
coronary artery bypass grafting (CABG), 19% in Total Hip Arthroplasty, and 18% in
Total Knee Arthroplasty. Medicare expenditure differences between the highest and
lowest deciles were because of a 5-fold difference for COL and 3-fold difference
for CABG in index hospitalization cost. In contrast, for orthopedic procedures,
there were 47- to 80-fold post-acute care expenditures between highest and lowest
deciles. In multivariable analyses, patients with >=3 comorbidities had
significantly higher costs than healthier patients. CONCLUSION: We found that a
subset of multimorbid patients was responsible for a disproportionate share of
total Medicare spending, but the individual components of spending vary by
procedure. These findings suggest that targeting high-cost Medicare patients (ie,
hot spotting) for cost containment efforts would be a potentially effective
strategy to reduce costs in surgical populations.
PMID- 29342020
TI - Editorial (Spring) Board? Gender Composition in High-impact General Surgery
Journals Over 20 Years.
AB - OBJECTIVE: To quantify gender composition of 10 high-impact general surgery
journals, delineate how board composition has changed over time, and evaluate
qualification metrics by gender. BACKGROUND: Underrepresentation of women on
editorial boards may contribute to the gender-based achievement gap in surgery.
METHODS: We performed a cross-sectional analysis of the editorial board gender
composition among 10 high-impact general surgery journals in 1997, 2007, and
2017. Univariate and multivariate regression analyses were used to assess
differences in editors' H-indices, academic rank, and number of advanced degrees.
Differences in editor turnover and multiple board positions were evaluated for
each time interval. RESULTS: Over 20 years, the proportion of women on editorial
boards increased from 5% to 19%. After controlling for time since board
certification, no differences between men and women's number of advances degrees,
H-indices, or academic rank remained significant. Women and men were equally
likely to hold multiple board positions (1997 P = 0.74; 2007 P = 0.42; 2017 P =
0.69), but men's editorial board tenure was longer across each time interval
(1997-2007 P = 0.003; 2007-2017 P < 0.001; 1997-2017 P = 0.01). CONCLUSIONS:
Women surgeons have a small but growing presence on surgical editorial boards,
and gender-based qualification differences are likely attributable to practice
length. Men's longer tenure on editorial boards may drive some of the observed
disparity by limiting new appointment opportunities. Strategies such as imposing
term limits or instituting merit-based performance reviews may help editorial
boards capture the field's changing demographics.
PMID- 29342021
TI - Nonoperative Management of Perforated Hollow Viscera in a Palliative Care Unit.
PMID- 29342023
TI - Physiatry Reviews for Evidence in Practice Second-Order Peer Review: Does Massage
Therapy Have Value in the Treatment for Tension Type Headache?
PMID- 29342022
TI - Association Between Altered Hip Extension and Kinetic Gait Variables.
AB - Kinematic and kinetic outcome measures are tightly linked in walking. Although
altering motor output is a major goal of gait rehabilitation, little is
understood regarding the relationship between altering a single kinematic
variable and kinetic outcome changes. We designed a strategy to isolate hip
extension alterations during walking on a treadmill to assess the change in
kinetic outcomes. Ten healthy individuals walked on an instrumented split-belt
treadmill with motion capture to calculate hip extension and kinetic outcomes at
the following five different randomized cadences: self-selected cadence, self
selected +/- 10%, and self-selected +/- 20%. The treadmill speed was held
constant at the individual's self-selected walking speed, forcing cadence changes
to result in successful alterations to hip extension, varying 8.3 degrees from
the self-selected -20% to +20% cadence conditions. Kinetic outcomes demonstrated
similar alterations. Hip extension changes at each cadence significantly
correlated with kinetic changes in propulsive impulse (r = 0.852, P < 0.001),
peak ankle power (r = 0.473, P = 0.002), and ankle plantarflexion work (r =
0.762, P < 0.001). These results demonstrate that kinetic outcomes are highly
alterable in response to a kinematic gait change. This clinically relevant
finding highlights the potential to improve motor output in individuals during
rehabilitation by altering gait patterns to achieve more optimal limb positions.
PMID- 29342024
TI - Clinical profile of patients with heart failure can predict rehospitalization and
quality of life.
AB - BACKGROUND: The aim of this retrospective study was to identify clinical, humoral
and echocardiographic variables predicting rehospitalization and poor quality of
life (QOL) in patients with reduced or mid-range ejection fraction heart failure.
METHODS: From 2009 to 2012, 310 patients were admitted having signs and symptoms
of heart failure with reduced ejection fraction. All the patients were followed
by phone, calling the patients or the referring general practitioner. The
Minnesota Living with Heart Failure Questionnaire (MLHFQ) was used as the
instrument to evaluate QOL: MLHFQ less than 24 is a good QOL, 24-45 is moderate
QOL and more than 45 is poor QOL. The primary event was poor QOL and/or
rehospitalization at 4 years. RESULTS: Seventy-nine patients died at median time
of 21 months; 4-year survival was 72 +/- 3%. Rehospitalization due to heart
failure was recorded in 60 cases. Among 231 survivors, MLHFQ score was good in 99
(42%), moderate in 50 (21%) and poor in 88 (37%). Four-year freedom from death,
poor QOL or rehospitalization was 51 +/- 3%. Multivariable analysis identified
the following risk factors: heart rate at discharge at least 70 bpm, ischemic
heart disease, atrial fibrillation, hypercholesterolemia, chronic pulmonary
disease, N-terminal pro brain natriuretic peptide at discharge, severe tricuspid
regurgitation and mitral regurgitation more than moderate. CONCLUSION: Clinical,
laboratory and echocardiographic profile is crucial to predict long-term QOL of
patients admitted for heart failure.
PMID- 29342025
TI - Pictorial Representation of Joint Involvement in Different Types of
Spondyloarthropathy.
PMID- 29342026
TI - Reflections on a life in menopause.
PMID- 29342027
TI - Response to letter to editor.
PMID- 29342028
TI - Lymphedema-Distichiasis Syndrome in a Male Patient Followed for 16 Years.
AB - Distichiasis is a challenging condition that may require multiple surgical
interventions. Besides ophthalmologic concerns in children, distichiasis may be
part of the lymphedema-distichiasis syndrome, which presents with lymphedema of
variable time of onset. Other significant systemic disorders such as coarctation
of the aorta and varicose veins have been reported in association with this
syndrome and must be reviewed for proper patient care. The authors report the
case of a 22-year-old male patient who had been treated for distichiasis and
followed for 16 years. At his initial evaluation, at 6 years of age, he presented
solely with ocular complaints due to distichiasis. Only after 13 years of
repeated ophthalmic treatments and continuous follow up, lymphedema was observed.
Lymphedema-distichiasis syndrome diagnosis must be considered in children with
distichiasis, even in the absence of lymphedema.
PMID- 29342029
TI - Association of Involutional Lower Eyelid Entropion with Reduced Upper Eyelid
Position Relative to the Corneal Light Reflex: Quantification of Facial
Asymmetry.
AB - PURPOSE: To investigate the association between upper eyelid position relative to
the corneal light reflex (MRD1) and to delineate an association between eyelid
height and involutional lower eyelid entropion. METHODS: Retrospective study of
patients presenting for entropion repair to an academic ophthalmic plastic
surgery service. A total of 111 patients were included in the study; 95 had
unilateral involutional lower eyelid entropion, and 16 had bilateral lower eyelid
entropion. Patients with a history of previous eyelid surgery, trauma, upper
eyelid entropion, or cicatricial changes were excluded from the study. RESULTS:
Of the 95 patients with unilateral involutional lower eyelid entropion, 45
(47.4%) had a lesser MRD1 on the side ipsilateral to the involutional lower
eyelid entropion. In this unilateral group, the mean MRD1 (+/- standard
deviation) on the ipsilateral to the involutional lower eyelid entropion was 2.9
(+/-1.2) mm, while the mean MRD1 on the contralateral side was 3.3 (+/-1.0) mm.
This difference was 0.4 mm and was statistically significant (p < 0.0001). Most
patients with unilateral involutional entropion demonstrated a right-sided
involutional lower eyelid entropion (56 of 95; 58.9%), although this finding was
not statistically significant (p = 0.083). The frequency of true blepharoptosis
(MRD1 <= 2.0 mm) was 24 of 95 (25.3%) in the unilateral involutional entropion
group and was even higher in the bilateral involutional lower eyelid entropion
group, with 7 of 16 (43.8%) patients exhibiting bilateral blepharoptosis.
CONCLUSIONS: Patients presenting with involutional lower eyelid entropion tend to
have a relatively reduced MRD1 on the ipsilateral (affected) side. When both
lower eyelids are affected by involutional entropion, the reduced MRD1 tends to
be more pronounced.
PMID- 29342030
TI - Mesenchymal Chondrosarcoma of the Lacrimal Gland.
AB - A 23-year-old woman presented with right-sided painless proptosis that developed
in 12 months. MRI studies demonstrated a well-delineated tumorous enlargement of
the right lacrimal gland with homogenous signal intensity and compressing the
globe. The tumor was removed totally and in 1 piece with the tentative diagnosis
of a pleomorphic adenoma. Pathologic examination revealed biphasic neoplastic
elements, which were composed of the cartilaginous matrix and small round cell
component. Immunohistopathological examination showed positive CD99 staining and
negative reaction to S100, panCK, and CD15. The patient then received a total of
64 Gy orbital radiotherapy in 32 fractionations. There has been no recurrence or
metastasis during 14 months of follow up. This case showed that mesenchymal
chondrosarcoma may arise from the lacrimal gland and must be considered in the
differential diagnosis of lacrimal gland tumors in young adults.
PMID- 29342031
TI - Adenocarcinoma of Pigmented Ciliary Epithelium in a Child With Aicardi Syndrome
and Congenital Microphthalmia With Cyst.
AB - A 5-year-old girl with Aicardi syndrome and microphthalmia with cyst of the OD
presented with progressive enlargement of the cyst causing pain. Microophthalmia
with inferior cyst (35 * 25 * 12 mm) was noted at birth, and Aicardi syndrome was
diagnosed at 10 months by the presence of the classic triad of callosal agenesis,
infantile spasms, and chorioretinal lacunae. She underwent enucleation with cyst
resection, and subsequent reconstruction with a dermis fat graft. Histopathologic
study revealed adenocarcinoma of the pigmented ciliary epithelium. Full-body
metastatic workup was negative. Adenocarcinoma of the pigmented ciliary
epithelium is an extremely rare eye tumor with only 4 documented cases in the
literature, none arising in a microophthalmic eye with cyst. Aicardi syndrome is
also a rare disease that has been associated with increased incidence of
malignancy and ocular abnormalities, but has never been described in association
with microophthalmia with cyst or with adenocarcinoma of the pigmented ciliary
epithelium. Herein, the authors present a review of the case and relevant
literature.
PMID- 29342032
TI - Angiomatosis of the Orbit: Clinical, Imaging, and Histologic Findings.
AB - Angiomatosis is a complex vascular malformation that denotes a clinically
extensive hemangioma, which either involves multiple tissue planes or extensively
infiltrates 1 type of tissue. It is a rare condition characterized by diffuse
proliferation of blood vessels admixed with fat and fibrotic tissue. Typically,
this process involves the limbs in multiple tissue planes, including dermis,
subcutis, muscle, and bone. In this report, the authors present the first case of
angiomatosis infiltrating the orbit, controlled effectively with a combination of
systemic steroids, radiation, and beta-blocker therapy. The characteristic
imaging and histologic features and management options are discussed.
PMID- 29342033
TI - Meningoencephalocele and Cerebrospinal Fluid Leak Complicating Orbital
Decompression.
AB - A 51-year-old man who had undergone right orbital decompression 5 months earlier
developed a meningoencephalocele extending in the right sphenoid sinus through a
skull base defect of the right ethmoid, sphenoid, and frontal bones. The authors
report the third case to their knowledge of meningoencephalocele with
cerebrospinal fluid leak after orbital decompression and discuss its management
and measures that can be taken to prevent this rare but serious complication.
PMID- 29342034
TI - Atypical Presentation of Squamous Papilloma.
PMID- 29342036
TI - Trends in Intraoperative Testing During Cochlear Implantation.
AB - OBJECTIVE: No consensus guidelines exist regarding intraoperative testing during
cochlear implantation and wide variation in practice habits exists. The objective
of this observational study was to survey otologists/neurotologists to understand
practice habits and overall opinion of usefulness of intraoperative testing.
STUDY DESIGN: Cross-sectional survey. SETTING: A web-based survey was sent to 194
practicing Otologists/Neurotologists. MAIN OUTCOME MEASURES: Questions included
practice setting and experience, habits with respect to electrodes used,
intraoperative testing modalities used, overall opinion of intraoperative
testing, and practice habits in various scenarios. RESULTS: Thirty-nine of 194
(20%) completed the survey. For routine patients, ECAPs and EIs were most
commonly used together (38%) while 33% do not perform testing at all. Eighty-nine
percent note that testing "rarely" or "never" changes management. Fifty-one
percent marked the most important reason for testing is the reassurance provided
to the family and/or the surgeon. CONCLUSION: Intraoperative testing habits and
opinions regarding testing during cochlear implantation vary widely among
otologic surgeons. The majority of surgeons use testing but many think there is
minimal benefit and that surgical decision-making is rarely impacted. The
importance of testing may change as electrodes continue to evolve.
PMID- 29342035
TI - Systematic Review of Hearing Preservation After Radiotherapy for Vestibular
Schwannoma.
AB - OBJECTIVE: To determine the long-term hearing preservation rate for spontaneous
vestibular schwannoma treated by primary radiotherapy. DATA SOURCES: The
MEDLINE/PubMed, Web of Science, Cochrane Reviews, and EMBASE databases were
searched using a comprehensive Boolean keyword search developed in conjunction
with a scientific librarian. English language papers published from 2000 to 2016
were evaluated. STUDY SELECTION: Inclusion criteria: full articles, pretreatment
and posttreatment audiograms or audiogram based scoring system, vestibular
schwannoma only tumor type, reported time to follow-up, published after 1999, use
of either Gamma Knife or linear accelerator radiotherapy. EXCLUSION CRITERIA:
case report or series with fewer than five cases, inadequate audiometric data,
inadequate time to follow-up, neurofibromatosis type 2 exceeding 10% of study
population, previous treatment exceeding 10% of study population, repeat
datasets, use of proton beam therapy, and non-English language. DATA EXTRACTION:
Two reviewers independently analyzed papers for inclusion. Class A/B, 1/2 hearing
was defined as either pure tone average less than or equal to 50 db with speech
discrimination score more than or equal to 50%, American Academy of
Otolaryngology-Head & Neck Surgery (AAO-HNS) Hearing Class A or B, or Gardner
Robertson Grade I or II. Aggregate data were used when individual data were not
specified. DATA SYNTHESIS: Means were compared with student t test. CONCLUSIONS:
Forty seven articles containing a total of 2,195 patients with preserved Class
A/B, 1/2 hearing were identified for analysis. The aggregate crude hearing
preservation rate was 58% at an average reporting time of 46.6 months after
radiotherapy treatment. Analysis of time-based reporting shows a clear trend of
decreased hearing preservation extending to 10-year follow-up. This data
encourages a future long-term controlled trial.
PMID- 29342037
TI - Preservation of Cells of the Organ of Corti and Innervating Dendritic Processes
Following Cochlear Implantation in the Human: An Immunohistochemical Study.
AB - HYPOTHESIS: This study evaluates the degree of preservation of hair cells,
supporting cells, and innervating dendritic processes after cochlear implantation
in the human using immunohistochemical methods. BACKGROUND: Surgical insertion of
a cochlear implant electrode induces various pathologic changes within the
cochlea including insertional trauma, foreign body response, inflammation,
fibrosis, and neo-osteogenesis. These changes may result in loss of residual
acoustic hearing, adversely affecting the use of hybrid implants, and may result
in loss of putative precursor cells, limiting the success of future regenerative
protocols. METHODS: Twenty-eight celloidin-embedded temporal bones from 14
patients with bilateral severe to profound sensorineural hearing loss and
unilateral cochlear implants were studied. Two sections including the modiolus or
basal turn from each temporal bone were stained using antineurofilament,
antimyosin-VIIa, and antitubulin antibodies in both the implanted and unimplanted
ears. RESULTS: Inner and outer hair cells: Immunoreactivity was reduced
throughout the implanted cochlea and in the unimplanted cochlea with the
exception of the apical turn.Dendritic processes in the osseous spiral lamina:
Immunoreactivity was significantly less along the electrode of the implanted
cochlea than in the other segments.Inner and outer pillars, inner and outer
spiral bundles, and Deiters' cells: Immunoreactivity was similar in the implanted
and unimplanted cochleae. CONCLUSION: Insertion of a cochlear implant electrode
may significantly affect the inner and outer hair cells both along and apical to
the electrode, and dendritic processes in the osseous spiral lamina along the
electrode. There was less effect on pillar cells, Deiters' cells, and spiral
bundles.
PMID- 29342038
TI - Utility of Noncontrast Magnetic Resonance Imaging for Detection of Recurrent
Vestibular Schwannoma.
AB - BACKGROUND: Gadolinium-enhanced T1-weighted magnetic resonance imaging (MRI)
(T1WI) is the conventional imaging technique of choice to detect vestibular
schwannoma (VS) recurrence or regrowth, despite suboptimal specificity secondary
to enhancing postoperative changes. Furthermore, recent concerns regarding the
accumulation of gadolinium in body tissues have led for a call to reduce the
number of contrast-enhanced examinations. The objective of the current study is
to evaluate the diagnostic accuracy of high-resolution noncontrast (three
dimensional [3D] T2) MRI relative to gadolinium-enhanced T1WI in the detection of
VS recurrence after resection. METHODS: Following Institutional Review Board
approval, 13 consecutive postoperative patients with VS recurrence or regrowth
were identified from a prospectively maintained clinical database in which
recurrence was determined by progression on serial postoperative MRI examination.
Three blinded neuroradiologists retrospectively evaluated a total of 41
postoperative MRI examinations from these patients using only gadolinium-enhanced
T1WI and 3D T2 MRI for recurrence or regrowth. Interobserver agreement,
differences in detection between the two sequences, and the sensitivity and
specificity of 3D T2 MRI were assessed. RESULTS: Fifteen of the 41 postoperative
MRIs demonstrated progression, as determined by examiner consensus on the
gadolinium-enhanced T1WI. Agreement, measured using Krippendorff's alpha, was
0.82 for the 3D T2 images and 0.83 for the contrast-enhanced T1WI. All the three
examiners demonstrated no difference in the detection of progression between the
two sequences (McNemar's test p values 0.69 for examiner 1, 0.63 for examiner 2,
and 0.99 for examiner 3). The sensitivity of 3D T2 was 0.78 (CI 0.60-0.96), while
the specificity was 0.94 (CI 0.86-1.00). CONCLUSION: Noncontrast high-resolution
3D T2 MRI seems sufficient to assess for recurrence or regrowth after VS
resection. The results of this study have implications for reducing cost, time,
and adverse events associated with gadolinium administration in this population
requiring serial follow-up examinations. These promising, yet preliminary
findings warrant confirmation with a larger prospective cohort of patients.
PMID- 29342039
TI - An Optimal Partial Ossicular Prosthesis Should Connect Both to the Tympanic
Membrane and Malleus: A Temporal Bone Study Using Laser Doppler Vibrometry.
AB - OBJECTIVE: To compare stapes vibrations in different partial ossicular
replacement prosthesis (PORP) applications. METHODS: Stapedial vibrations were
measured on fresh frozen human temporal bones with laser Doppler vibrometry.
Eight different types of common ossiculoplasty methods were compared regarding
recovery of stapes vibrations in relation with the normal ossicular chain. The
PORPs were divided into three groups: 1) PORPs with the lateral contact only with
the tympanic membrane, 2) PORPs with lateral contact only to the malleus handle,
and 3) PORPs with lateral contact with both the malleus handle and the tympanic
membrane. RESULTS: The PORPs with lateral contact only to the malleus handle
performed better than the PORPs with lateral contact to the tympanic membrane
only at 2 kHZ, but the best recovery was found in the group with contact both to
the malleus handle and the tympanic membrane. CONCLUSION: The best sound
transmission might be achieved by placing a PORP in contact with both the
tympanic membrane and the handle of the malleus.
PMID- 29342040
TI - Unilateral Sensorineural Hearing Loss Presenting With Bilateral Temporal Bone
Lesions.
PMID- 29342041
TI - History of the Research Fund of the American Otological Society.
PMID- 29342043
TI - The American Otological Society at its Sesquicentennial: Insights Into the
Society's Formative Years.
AB - OBJECTIVE: To elucidate the sequence of events which led to the formation of the
American Otological Society (AOS) in 1868 and to examine the lives and
contributions of the nine founding members of the Society. METHODS: Study of
primary historical documents, biographical material, and previous histories of
the AOS. RESULTS: Earlier treatments of the history of the AOS minimally covered
the events and personalities from the Society's formative period. The founders of
the AOS were much influenced by recent advances in European Otology and the
success of the nascent American Ophthalmological Society which had been founded
in 1864. The AOS has long credited Elkanah Williams as its first president of the
AOS, although he never actually served in this role and was not a contributor to
otological literature. Documents suggest that 30 years old New York physician
Daniel Bennett St John Roosa, recently returned from a grand tour of the leading
European otological centers, was the principal advocate for the creation of the
AOS. CONCLUSIONS: The 1860s were a pivotal period in the maturation of American
Otology. Previously, most "aurists" were widely considered to be charlatans who
practiced unscientifically and often unscrupulously. The AOS founder generation
were a group of Ophthalmologists who strove to elevate otology from being a
lesser appendage of the mother field to becoming a respected and scientifically
based medical specialty in its own right.
PMID- 29342042
TI - Long-term Administration of Salicylate-induced Changes in BDNF Expression and
CREB Phosphorylation in the Auditory Cortex of Rats.
AB - HYPOTHESIS: We investigated whether salicylate induces tinnitus through
alteration of the expression levels of brain-derived neurotrophic factor (BDNF),
proBDNF, tyrosine kinase receptor B (TrkB), cAMP-responsive element-binding
protein (CREB), and phosphorylated CREB (p-CREB) in the auditory cortex (AC).
BACKGROUND: Salicylate medication is frequently used for long-term treatment in
clinical settings, but it may cause reversible tinnitus. Salicylate-induced
tinnitus is associated with changes related to central auditory neuroplasticity.
Our previous studies revealed enhanced neural activity and ultrastructural
synaptic changes in the central auditory system after long-term salicylate
administration. However, the underlying mechanisms remained unclear. METHODS:
Salicylate-induced tinnitus-like behavior in rats was confirmed using gap
prepulse inhibition of acoustic startle and prepulse inhibition testing, followed
by comparison of the expression levels of BDNF, proBDNF, TrkB, CREB, and p-CREB.
Synaptic ultrastructure was observed under a transmission electron microscope.
RESULTS: BDNF and p-CREB were upregulated along with ultrastructural changes at
the synapses in the AC of rats treated chronically with salicylate (p < 0.05,
compared with control group). These changes returned to normal after 14 days of
recovery (p > 0.05). CONCLUSION: Long-term administration of salicylate increased
BDNF expression and CREB activation, upregulated synaptic efficacy, and changed
synaptic ultrastructure in the AC. There may be a relationship between these
factors and the mechanism of tinnitus.
PMID- 29342045
TI - Jugular Foramen Meningioma.
PMID- 29342044
TI - Elevated Level of Myeloperoxidase-Deoxyribonucleic Acid Complex in the Middle Ear
Fluid Obtained From Patients With Otitis Media Associated With Antineutrophil
Cytoplasmic Antibody-associated Vasculitis.
AB - OBJECTIVE: The purpose was to explore the presence of myeloperoxidase (MPO)
deoxyribonucleic acid (DNA) complex as a surrogate marker of neutrophil
extracellular traps (NETs) in the middle ear fluid, and to clarify the
correlation between its quantifiable level and hearing outcome in patients with
otitis media associated with antineutrophil cytoplasmic antibody (ANCA)
associated vasculitis (AAV). STUDY DESIGN: Prospective study. SETTING: Tertiary
referral center. PATIENTS: Nine AAV patients presenting with otitis media.
INTERVENTION: Collection of the fluid samples from middle ear. MAIN OUTCOME
MEASURE: The quantifiable levels of MPO-DNA complex using an enzyme-linked
immunosorbent assay. RESULTS: The quantifiable levels of MPO-DNA complex in
patients with AAV were significantly higher than those in controls (p < 0.001).
In particular, both ANCA-positive and -negative cases indicated higher levels of
MPO-DNA complex compared with the controls (p = 0.004 and p = 0.006,
respectively). The significant negative correlations were observed between the
level of MPO-DNA complex and the functional hearing values for air (r = -0.82, p
= 0.009) and bone conduction (r = -0.73, p = 0.028), respectively. CONCLUSION:
This analysis is the first to reveal the presence of elevated levels of MPO-DNA
complex in the middle ear fluid, suggesting the pathogenic role of NETs in otitis
media associated with AAV. NETs may be a valuable biomarker for use in clinical
decision-making and predicting hearing outcome, regardless of ANCA status.
PMID- 29342046
TI - Large Facial Nerve Schwannoma With Extensive Temporal Bone Destruction.
PMID- 29342047
TI - Direction-fixed and Direction-changing Positional Nystagmus in Ramsay Hunt
Syndrome.
AB - OBJECTIVES: To investigate the incidence of positional nystagmus (PN) using a
head-roll test in patients with Ramsay Hunt syndrome with vertigo (RHS_V) and
discuss possible mechanisms. STUDY DESIGN: Retrospective study. SETTING: Tertiary
referral academic medical center. PATIENTS: Twenty-eight patients with RHS_V were
enrolled. MAIN OUTCOME MEASURE: Eye movements were recorded at positions of head
roll to the right or left, and PN was classified as direction-fixed or direction
changing. Vestibular function tests including caloric test were performed.
RESULTS: Direction-fixed nystagmus beating away from the affected side was the
most common type of PN (61%), followed by direction-changing geotropic type
(18%), direction-fixed nystagmus beating toward the affected side (14%), and
direction-changing apogeotropic type (7%). The duration of nystagmus was longer
than 60 seconds in all patients exhibiting direction-changing PN. Postcontrast T1
weighted internal auditory canal (IAC) magnetic resonance imaging showed
enhancement of not only the facial and vestibulocochlear nerves, but also the
inner ear structures or dura along the IAC, suggesting inflammatory changes
within the labyrinthine membrane or IAC dura. CONCLUSION: Although direction
fixed PN was more commonly observed (75%), direction-changing PN was also
observed in some RHS_V patients (25%). The mechanism of direction-changing PN may
be, at least in part, explained by the alteration of specific gravity of the
lateral semicircular canal cupula or endolymph due to inflammation in the inner
ear membrane.
PMID- 29342048
TI - External Ear Arteriovenous Malformation.
PMID- 29342049
TI - The Impact of the Transcanal Endoscopic Approach and Mastoid Preservation on
Recurrence of Primary Acquired Attic Cholesteatoma.
AB - OBJECTIVE: We aim to investigate the factors associated with recurrent disease
following surgery for primary acquired attic cholesteatoma. We hypothesize that
minimal invasive, mucosal sparing operation techniques have beneficial effects on
the outcome in terms of recurrence. STUDY DESIGN: Retrospective study. SETTING:
Tertiary referral center. PARTICIPANTS: A total of 110 patients presenting with
primary acquired attic cholesteatoma were enrolled in the study. Patients
undergoing revision surgery or a canal wall down procedure, as well as patients
with residual disease were excluded from the study. MAIN OUTCOME MEASURES: During
follow-up recurrence was assessed and classified into normal, self-cleaning
retraction pockets, or recurrent cholesteatoma requiring revision surgery.
RESULTS: We observed during follow-up statistically significant decrease (p =
0.036) in the occurrence of retraction pockets and recurrence in patients
operated by the transcanal endoscopic approach (n = 55, 11% re-retraction, 9%
recurrence) compared with those who underwent a canal wall up procedure (n = 55,
16% re-retraction, 22% recurrence). However, the multivariate model did not
demonstrate statistically significant predictors regarding the outcome. Moreover,
the preservation or direct reconstruction of the ossicular chain had a beneficial
effect on the outcome. We observed 11% re-retraction and 9% recurrence in cases
with preserved or reconstructed ossicular chain versus 18% re-retraction and 24%
recurrence (p = 0.011) in cases of nonpreserved or non-reconstructed ossicular
chain. A score was established according to the intraoperative mucosal damage and
correlated to the occurrence of recurrence (p = 0.02). The risk of recurrence
increased by 23.6% (95% confidence interval: 3.22-48.1) with each additional
mucosal damage site. CONCLUSION: Transcanal endoscopic approaches that preserve
the mastoid may play an important role in preventing recurrence and underscores
the importance of the mucosa and mastoid air cells on middle ear homeostasis.
PMID- 29342050
TI - Intraoperative Cochlear Implant Device Testing Utilizing an Automated Remote
System: A Prospective Pilot Study.
AB - INTRODUCTION: Intraoperative cochlear implant device testing provides valuable
information regarding device integrity, electrode position, and may assist with
determining initial stimulation settings. Manual intraoperative device testing
during cochlear implantation requires the time and expertise of a trained
audiologist. The purpose of the current study is to investigate the feasibility
of using automated remote intraoperative cochlear implant reverse telemetry
testing as an alternative to standard testing. METHODS: Prospective pilot study
evaluating intraoperative remote automated impedance and Automatic Neural
Response Telemetry (AutoNRT) testing in 34 consecutive cochlear implant surgeries
using the Intraoperative Remote Assistant (Cochlear Nucleus CR120). In all cases,
remote intraoperative device testing was performed by trained operating room
staff. A comparison was made to the "gold standard" of manual testing by an
experienced cochlear implant audiologist. Electrode position and absence of tip
fold-over was confirmed using plain film x-ray. RESULTS: Automated remote reverse
telemetry testing was successfully completed in all patients. Intraoperative x
ray demonstrated normal electrode position without tip fold-over. Average
impedance values were significantly higher using standard testing versus CR120
remote testing (standard mean 10.7 kOmega, SD 1.2 vs. CR120 mean 7.5 kOmega, SD
0.7, p < 0.001). There was strong agreement between standard manual testing and
remote automated testing with regard to the presence of open or short circuits
along the array. There were, however, two cases in which standard testing
identified an open circuit, when CR120 testing showed the circuit to be closed.
Neural responses were successfully obtained in all patients using both systems.
There was no difference in basal electrode responses (standard mean 195.0 MUV, SD
14.10 vs. CR120 194.5 MUV, SD 14.23; p = 0.7814); however, more favorable (lower
MUV amplitude) results were obtained with the remote automated system in the
apical 10 electrodes (standard 185.4 MUV, SD 11.69 vs. CR120 177.0 MUV, SD 11.57;
p value < 0.001). CONCLUSION: These preliminary data demonstrate that
intraoperative cochlear implant device testing using a remote automated system is
feasible. This system may be useful for cochlear implant programs with limited
audiology support or for programs looking to streamline intraoperative device
testing protocols. Future studies with larger patient enrollment are required to
validate these promising, but preliminary, findings.
PMID- 29342052
TI - Preauricular Approach for Cholesteatoma Resection After Surgical Overclosure of
the External Auditory Canal and Cochlear Implantation.
AB - : Chronic suppurative otitis media can have long-term effects on hearing if not
managed effectively. When combined with cholesteatoma the condition may require
creation of an open mastoid cavity. Recurrence of cholesteatoma is a concern when
cochlear implantation is performed with overclosure of the external auditory
meatus. A 61-year-old female with recurrent cholesteatoma in this setting was
treated using a preauricular approach to provide adequate visualization while
preventing the need to remove the implant or risking injury to the internal
components. This technique would be useful in similar patients to prevent
morbidity from removal and reinsertion of a cochlear implant.
PMID- 29342051
TI - Does Hospital Volume Affect Outcomes in Patients Undergoing Vestibular Schwannoma
Surgery?
AB - OBJECTIVE: To determine the effect of hospital surgical case volume on the
outcomes of vestibular schwannoma surgery. STUDY DESIGN: Retrospective case
review. SETTING: University HealthSystem Consortium member hospitals (includes
nearly every US academic medical center). PATIENTS: Three thousand six hundred
ninety-seven patients who underwent vestibular schwannoma resection over a 3-year
timespan (2012-2015) grouped by race, age, comorbidities, payer, and sex.
INTERVENTION: Surgical resection of vestibular schwannoma. MAIN OUTCOME MEASURES:
Morbidity and mortality following vestibular schwannoma excision are compared by
hospital volume (low, medium, and high) including deciles. RESULTS: There was
significantly longer length of stay (p <= 0.005) among groups with low-volume
hospitals followed by medium-volume hospitals and high-volume hospitals. Low
volume hospitals had a significantly higher rate of complications including
stroke, aspiration, and respiratory failure (p <= 0.0175). Patient
characteristics of age, sex, sex, and baseline comorbidities were similar between
hospital groups. However, patients at high-volume hospitals were more likely to
be Caucasian (83.1%, p = 0.0001) and have private insurance (76.7%, p < 0.0001).
There was a strong negative correlation between complication rates and hospital
volume (r = -0.8164, p = 0.0040). CONCLUSION: The volume of vestibular schwannoma
surgeries performed at a hospital impacts length of stay and rates of
postoperative complications. Demographics among hospital groups were similar
though high-volume hospitals had significantly more patients who were privately
insured and Caucasian.
PMID- 29342053
TI - Gradual Symmetric Progression of DFNA34 Hearing Loss Caused by an NLRP3 Mutation
and Cochlear Autoinflammation.
AB - OBJECTIVE: To characterize the audiometric phenotype of autosomal-dominant DFNA34
hearing loss (HL) caused by a missense substitution in the NLRP3 gene. NLRP3
encodes a critical component of the NLRP3 inflammasome that is activated in
innate immune responses. STUDY DESIGN: This study was conducted under protocol 01
DC-0229 approved by the NIH Combined Neurosciences IRB. We performed medical and
developmental history interviews and physical and audiological examinations of
affected individuals with DFNA34 HL caused by the p.Arg918Gln mutation of NLRP3.
We retrospectively reviewed audiological reports, when available, from other
health care centers. SETTING: Federal biomedical research facility. SUBJECTS:
Eleven members of a North American family segregating p.Arg918Gln. MAIN OUTCOME
MEASURES: Pure-tone thresholds, rates of pure-tone threshold progression, and
speech discrimination scores. RESULTS: Eight subjects had bilateral sensorineural
HL with an onset in the late 2nd to 4th decade of life. Slowly progressive HL
initially primarily affected high frequencies. Low and middle frequencies were
affected with advancing age, resulting in moderate HL with a downsloping
audiometric configuration. The average annual threshold deterioration was 0.9 to
1.5 dB/yr. Speech recognition scores ranging from 60 to 100% were consistent with
cochlear, but not retrocochlear, etiology. Three subjects (16, 22, and 32 yr old)
had normal hearing thresholds. CONCLUSION: DFNA34 HL has an onset during early
adulthood and progresses approximately 1.2 dB/yr.
PMID- 29342055
TI - Benefit of Preoperative Temporal Bone CT for Atraumatic Cochlear Implantation.
AB - HYPOTHESIS: Evaluate the benefit of preoperative surgical planning using computed
tomography (CT) for atraumatic cochlear implantation. BACKGROUND: The surgical
technique has a direct impact on hearing and structure preservation. Much
interest has been given to depth of electrode insertion. We focused on electrode
diameter depending on exposure of round window membrane (RWM) as calculated on
preoperative CT. METHODS: Measurements were calculated radiologically and
anatomically on 10 temporal bones. Results were compared with CT scans of a
control population. Thereafter, preoperative CT scan measurements were applied to
seven additional temporal bones that underwent cochlear implantation with the
insertion of two electrodes of different diameters (14 implantations) to validate
radiological analysis. RESULTS: RWM size was 1.5 +/- 0.2 mm on CT and 1.2 +/- 0.2
mm during dissection; posterosuperior bony overhang of round window niche was 1.1
+/- 0.1 mm on CT and 1.3 +/- 0.2 mm during dissection. There was no statistically
significant difference between radiological and anatomical measurements and
between radiological measurements of cadaveric temporal bones and control
population (p > 0.05 for both). Also, preoperative surgical planning was reliable
in the seven temporal bones implanted with two electrode types (accuracy 93%,
sensitivity 85.7%, specificity 100%) yielding no damage to intracochlear
structures. CONCLUSION: Difficulties to access RWM could be predicted on
preoperative CT of temporal bones and control population, which correlated well
with anatomical dissections and surgical findings during cochlear implantation.
According to CT planning, electrode insertion through RWM was feasible in most
patients, with or without drilling posterosuperior bony overhang of round window
niche. Promontory cochleostomy could be recommended when electrode apical
diameter exceeded maximal RWM exposure. There was no case of intracochlear trauma
on microdissections.
PMID- 29342054
TI - Multicenter US Clinical Trial With an Electric-Acoustic Stimulation (EAS) System
in Adults: Final Outcomes.
AB - OBJECTIVE: To demonstrate the safety and effectiveness of the MED-EL Electric
Acoustic Stimulation (EAS) System, for adults with residual low-frequency hearing
and severe-to-profound hearing loss in the mid to high frequencies. STUDY DESIGN:
Prospective, repeated measures. SETTING: Multicenter, hospital. PATIENTS: Seventy
three subjects implanted with PULSAR or SONATA cochlear implants with FLEX
electrode arrays. INTERVENTION: Subjects were fit postoperatively with an audio
processor, combining electric stimulation and acoustic amplification. MAIN
OUTCOME MEASURES: Unaided thresholds were measured preoperatively and at 3, 6,
and 12 months postactivation. Speech perception was assessed at these intervals
using City University of New York sentences in noise and consonant-nucleus
consonant words in quiet. Subjective benefit was assessed at these intervals via
the Abbreviated Profile of Hearing Aid Benefit and Hearing Device Satisfaction
Scale questionnaires. RESULTS: Sixty-seven of 73 subjects (92%) completed outcome
measures for all study intervals. Of those 67 subjects, 79% experienced less than
a 30 dB HL low-frequency pure-tone average (250-1000 Hz) shift, and 97% were able
to use the acoustic unit at 12 months postactivation. In the EAS condition, 94%
of subjects performed similarly to or better than their preoperative performance
on City University of New York sentences in noise at 12 months postactivation,
with 85% demonstrating improvement. Ninety-seven percent of subjects performed
similarly or better on consonant-nucleus-consonant words in quiet, with 84%
demonstrating improvement. CONCLUSION: The MED-EL EAS System is a safe and
effective treatment option for adults with normal hearing to moderate
sensorineural hearing loss in the low frequencies and severe-to-profound
sensorineural hearing loss in the high frequencies who do not benefit from
traditional amplification.
PMID- 29342056
TI - "Product" Versus "Process" Measures in Assessing Speech Recognition Outcomes in
Adults With Cochlear Implants.
AB - HYPOTHESES: 1) When controlling for age in postlingual adult cochlear implant
(CI) users, information-processing functions, as assessed using "process"
measures of working memory capacity, inhibitory control, information-processing
speed, and fluid reasoning, will predict traditional "product" outcome measures
of speech recognition. 2) Demographic/audiologic factors, particularly duration
of deafness, duration of CI use, degree of residual hearing, and socioeconomic
status, will impact performance on underlying information-processing functions,
as assessed using process measures. BACKGROUND: Clinicians and researchers rely
heavily on endpoint product measures of accuracy in speech recognition to gauge
patient outcomes postoperatively. However, these measures are primarily
descriptive and were not designed to assess the underlying core information
processing operations that are used during speech recognition. In contrast,
process measures reflect the integrity of elementary core subprocesses that are
operative during behavioral tests using complex speech signals. METHODS: Forty
two experienced adult CI users were tested using three product measures of speech
recognition, along with four process measures of working memory capacity,
inhibitory control, speed of lexical/phonological access, and nonverbal fluid
reasoning. Demographic and audiologic factors were also assessed. RESULTS: Scores
on product measures were associated with core process measures of speed of
lexical/phonological access and nonverbal fluid reasoning. After controlling for
participant age, demographic and audiologic factors did not correlate with
process measure scores. CONCLUSION: Findings provide support for the important
foundational roles of information processing operations in speech recognition
outcomes of postlingually deaf patients who have received CIs.
PMID- 29342058
TI - MRI Evaluation of Repaired Versus Unrepaired Interportal Capsulotomy in
Simultaneous Bilateral Hip Arthroscopy: A Double-Blind, Randomized Controlled
Trial.
AB - BACKGROUND: Techniques used in hip arthroscopy continue to evolve, and
controversy surrounds the need for capsular repair following this surgical
intervention. The purpose of this study was to evaluate the magnetic resonance
imaging (MRI) appearance of the hip capsule in patients with femoroacetabular
impingement (FAI) who underwent simultaneous bilateral hip arthroscopy through an
interportal capsulotomy with each hip randomized to undergo capsular repair or
not undergo such a repair. METHODS: This double-blind, randomized controlled
trial included 15 patients (30 hips), with a mean age of 29.2 years, who
underwent simultaneous bilateral hip arthroscopy utilizing a small (<3-cm)
interportal capsulotomy for the treatment of FAI. The first hip treated in each
patient was intraoperatively randomized to undergo capsular repair or no capsular
repair. The contralateral hip then received the opposite treatment. MRI was
performed at 6 and 24 weeks postoperatively, and the scans were analyzed by 2
musculoskeletal radiologists. The patients and the radiologists were blinded to
the treatment performed on each hip. Capsular dimensions were measured at the
level of the healing capsulotomy site and, for hips with a persistent defect, at
locations both proximal and distal to the defect. These values were then analyzed
at both time points to assess the rate and extent of capsular healing. RESULTS:
At 6 weeks postoperatively, a continuous hip capsule (with no apparent
capsulotomy defect) was observed in 8 hips treated with capsular repair and 3
hips without such a repair. Of the 19 hips with a discontinuous capsule at 6
weeks, 17 were available for follow-up at 24 weeks postoperatively; all 17
demonstrated progression to healing, with a contiguous appearance without defects
and no difference in capsular dimensions between treatment cohorts. CONCLUSIONS:
Arthroscopic repair of a small interportal hip capsulotomy site yields an
insignificant increase in the percentage of continuous hip capsules seen on MRI
at 6 weeks postoperatively compared with no repair. Repaired and unrepaired
capsulotomy sites progressed to healing with a contiguous appearance on MRI by 24
weeks postoperatively. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions
for Authors for a complete description of levels of evidence.
PMID- 29342057
TI - Audiologic Natural History of Small Volume Cochleovestibular Schwannomas in
Neurofibromatosis Type 2.
AB - OBJECTIVE: To characterize the audiometric natural progression in patient-ears
with small volume (<1,000 mm), treatment-naive cochleovestibular schwannomas
(CVSs) in Neurofibromatosis Type 2 (NF2). STUDY DESIGN: Prospective, longitudinal
cohort study. SETTING: Quaternary medical research institute. PATIENTS: One
hundred eleven ears in 71 NF2 patients with small, treatment-naive CVSs observed
from July 2006 to July 2016. INTERVENTION: Serial audiometric testing, including
pure tone audiometry, speech audiometry, and magnetic resonance imaging (MRI).
OUTCOME MEASURES: Four-frequency pure tone average (4f-PTA) of 0.5, 1, 2, and 4
kHz and word recognition score (WRS) were recorded. Their changes were compared
with MRI changes in CVS volume over time. Times to significant hearing loss (10
dB loss in 4f-PTA) and WRS based on 95% critical difference were measured.
RESULTS: Linear regression analysis showed a significant correlation with
baseline hearing level (4f-PTA) and internal auditory canal (IAC) tumor volume to
annual hearing decrease rate (AHDR) (p = 0.003, p = 0.0004). Hearing level at
baseline and tumor volume correlate with AHDR while tumor volume growth rate does
not. Two-way analysis of variance found significant differences in AHDR, risk of
significant hearing loss, and risk of critical difference in WRS based on
baseline hearing level (abnormal or normal) and IAC tumor volume (greater or less
than 200 mm). CONCLUSION: Subjects with normal baseline hearing and small IAC
tumor component had a low AHDR and low risk of significant hearing loss and may
warrant conservative management while the presence of baseline hearing loss and
large IAC volume resulted in higher ADHR and greater risk for further hearing
loss and may benefit from early treatment interventions.
PMID- 29342059
TI - Patients Living Alone Can Be Safely Discharged Directly Home After Total Joint
Arthroplasty: A Prospective Cohort Study.
AB - BACKGROUND: Despite the expense and potential hazards of inpatient
rehabilitation, there is a prevailing belief that patients living alone cannot be
safely discharged directly home after total joint arthroplasty. The purpose of
this study was to assess the safety and efficacy of direct home discharge for
patients living alone during convalescence after primary total joint
arthroplasty. METHODS: We prospectively studied 910 consecutive patients
undergoing primary, unilateral total hip arthroplasty or total knee arthroplasty
over an 8-month period. Patients discharged directly home who were living alone
for the first 2 weeks after the surgical procedure were identified as the
investigational group and those discharged to home and living with others
constituted the control group. The primary outcomes were 90-day complications and
unplanned clinical events, including readmissions, emergency department or urgent
care visits, and office visits. Functional outcomes, patient satisfaction, pain
relief, and return to daily function were also assessed. RESULTS: During the
study period, 874 patients (96%) were discharged directly home and only 36
patients (4%) were discharged to a rehabilitation facility. Of those discharged
home, 769 patients were included in the final analysis, including 138 patients
living alone and 631 patients living with others, and 105 patients were excluded
as they opted not to participate. Patients living alone more commonly stayed an
additional night in the hospital and utilized more home health services. There
was no increase in complications or unplanned clinical events for patients living
alone compared with those living with others. Further, no significant differences
in functional outcomes or pain relief were detected, and satisfaction scores were
equivalent after 90 days. CONCLUSIONS: Patients living alone had a safe and
manageable recovery when discharged directly home after total joint arthroplasty.
Extending the initial hospitalization and providing home health services on a
selected basis may be a more cost-effective approach than routine discharge to an
inpatient rehabilitation facility. LEVEL OF EVIDENCE: Therapeutic Level II. See
Instructions for Authors for a complete description of levels of evidence.
PMID- 29342060
TI - Creep and Wear in Vitamin E-Infused Highly Cross-Linked Polyethylene Cups for
Total Hip Arthroplasty: A Prospective Randomized Controlled Trial.
AB - BACKGROUND: Aseptic loosening, the most common indication for revision surgery in
total hip arthroplasty, can result from osteolysis caused by polyethylene (PE)
wear particles. PE wear is increased by age-related oxidation of PE and free
radicals emerging during irradiation cross-linking. Diffusion of vitamin E into
PE stabilizes free radicals to maintain the biomechanical properties of PE. The
purpose of this study was to determine whether vitamin E-infused highly cross
linked PE cups could reduce wear rates. METHODS: We performed a prospective
randomized controlled trial, in which 62 patients were allocated to 2 groups: a
study group that received a vitamin E-infused highly cross-linked PE (HXLPE/VitE)
cup and a control group that received an ultra-high molecular weight PE (UHMWPE)
cup. Using radiostereometric analysis, we measured the penetration of the femoral
head into the cup 7 days after surgery (baseline) and then again at 6 months and
at 1, 2, and 3 years later. RESULTS: Baseline variables did not differ
significantly between the groups. At 1, 2, and 3 years after surgery, the
HXLPE/VitE cup showed significantly less cumulative penetration (creep and wear)
than the UHMWPE cup (p = 0.004, p < 0.0001, and p < 0.0001, respectively). The
cumulative penetration after 3 years was 0.200 mm for the HXLPE/VitE cup versus
0.317 mm for the UHMWPE cup (p < 0.0001). From 1 to 3 years after surgery, after
creep had stabilized and further penetration was mainly due to wear, the mean
penetration increased only 0.04 mm in the HXLPE/VitE cup and 0.116 mm in the
UHMWPE cup. CONCLUSIONS: Our results confirm that wear rates over the first 3
years following surgery were lower in HXLPE/VitE cups than in UHMWPE cups. This
suggests that HXLPE/VitE cups may prevent osteolysis, implant loosening, and
eventually revision surgery. Long-term follow-up data continue to be collected to
confirm these findings. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions
for Authors for a complete description of levels of evidence.
PMID- 29342061
TI - The Effect of Alternative Bearing Surfaces on the Risk of Revision Due to
Infection in Minimally Stabilized Total Knee Replacement: An Analysis of 326,603
Prostheses from the Australian Orthopaedic Association National Joint Replacement
Registry.
AB - BACKGROUND: The effect of alternative bearing materials on the risk of revision
due to infection after total knee replacement remains uncertain. By reducing the
immunomodulating polyethylene wear-particle burden and with different substrate
bacterial adhesion properties, Oxinium oxidized zirconium and cross-linked
polyethylene (XLPE) could alter infection risk. The purpose of the current study
was to analyze the risk of revision for infection in 3 comparisons of bearing
combinations. METHODS: To evaluate the risk of revision for infection with XLPE,
cobalt-chromium (CoCr) on XLPE was compared with CoCr on non-cross-linked
polyethylene (NXLPE). To evaluate Oxinium, Oxinium-NXLPE was compared with CoCr
NXLPE, and to evaluate the possibility of an additional beneficial effect of
Oxinium on XLPE, Oxinium-XLPE was compared with CoCr-XLPE. The cumulative percent
revision (CPR) and hazard ratio (HR) for revision for infection in primary total
knee replacement for osteoarthritis were determined from registry data from
September 1, 1999, to December 31, 2015. Revisions within 6 months following the
primary surgery were censored from the analysis, while procedures with posterior
stabilized or fully stabilized total knee replacements as well as prostheses with
a known higher risk of revision were excluded. Analyses were stratified by age,
sex, and fixation type. RESULTS: Of the 326,603 included primary total knee
replacements, 1,511 (0.46%) were revised for infection. The risk of revision for
infection was lower for CoCr-XLPE compared with CoCr-NXLPE (HR = 0.74; 95%
confidence interval [CI] = 0.65 to 0.84; p < 0.001). This effect was apparent for
both male and female patients overall, all fixation types, antibiotic cement use,
those <65 years of age, and male patients >=65 years of age. However, for female
patients >=65 years of age, there was no difference. Overall, Oxinium-NXLPE had
the same revision risk as CoCr-NXLPE regardless of fixation; however, for
cemented fixation, subanalysis showed a lower risk for Oxinium-NXLPE compared
with CoCr-NXLPE (HR = 0.69; 95% CI = 0.51 to 0.94; p = 0.018). Oxinium-XLPE had
the same revision risk for infection as CoCr-XLPE overall, among male patients,
and when cemented fixation had been used. CONCLUSIONS: In this registry analysis,
CoCr-XLPE had a 26% lower risk of revision for infection than CoCr-NXLPE,
suggesting a reduction of wear particle-induced immunomodulation with XLPE.
Oxinium-XLPE had the same risk as CoCr-XLPE. Overall, Oxinium did not reduce the
infection risk. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for
Authors for a complete description of levels of evidence.
PMID- 29342062
TI - Potential Sex Bias Exists in Orthopaedic Basic Science and Translational
Research.
AB - BACKGROUND: Potential sex bias has been shown in general surgery basic science
and translational research, with unequal representation of male and female
specimens. Because basic science research forms the foundation for clinical
studies on which patient care is based, it is important that this research
equally consider both sexes. The purpose of this study was to determine if
potential sex bias exists in the basic science and translational orthopaedic
literature. METHODS: A systematic review was conducted of all articles published
in 2014 in The Journal of Bone & Joint Surgery, Clinical Orthopaedics and Related
Research, The Bone & Joint Journal, and the Journal of Orthopaedic Research
(JOR). All original research articles utilizing animals, cells, or cadavers were
included. The data abstracted included study type, sex of specimen studied, and
presence of sex-based reporting of data. A second review was performed of all
basic science articles published in JOR in 1994, 2004, and 2014 to compare sex
bias trends across 3 decades. Distributions of variables were compared using the
Fisher exact test, with significance defined as p < 0.05. RESULTS: Of 1,693
articles reviewed, 250 (15%) were included: 122 animal-based studies (49%), 71
cell-based studies (28%), and 57 human cadaver-based studies (23%). Overall,
authors in 88 studies (35%) did not report the sex of animals, cells, or cadavers
used. Of 162 studies in which the authors did report sex, 69 (43%) utilized male
only, 40 (25%) utilized female only, and 53 (33%) utilized both sexes. Of those
studies that used both sexes, authors in only 7 studies (13%) reported sex-based
results. A subanalysis of JOR articles across 3 decades revealed a significant
increase in studies specifying sex (p = 0.01) from 2004 to 2014. CONCLUSIONS:
Potential sex bias exists in orthopaedic surgery basic science and translational
research, with an overrepresentation of male specimens. CLINICAL RELEVANCE:
Inequality in sex representation must be addressed as basic science and
translational research creates the foundation for subsequent clinical research,
which ultimately informs clinical care.
PMID- 29342063
TI - Low Prevalence of Hip and Knee Arthritis in Active Marathon Runners.
AB - BACKGROUND: Existing evidence on whether marathon running contributes to hip and
knee arthritis is inconclusive. Our aim was to describe hip and knee health in
active marathon runners, including the prevalence of pain, arthritis, and
arthroplasty, and associated risk factors. METHODS: A hip and knee health survey
was distributed internationally to marathon runners. Active marathoners who
completed >=5 marathons and were currently running a minimum of 10 miles per week
were included (n = 675). Questions assessed pain, personal and family history of
arthritis, surgical history, running volume, personal record time, and current
running status. Multivariable analyses identified risk factors for pain and
arthritis. Arthritis prevalence in U.S. marathoners was compared with National
Center for Health Statistics prevalence estimates for a matched group of the U.S.
POPULATION: RESULTS: Marathoners (n = 675) with a mean age of 48 years (range,
18 to 79 years) ran a mean distance of 36 miles weekly (range, 10 to 150 miles
weekly) over a mean time of 19 years (range, 3 to 60 years) and completed a mean
of 76 marathons (range, 5 to 1,016 marathons). Hip or knee pain was reported by
47%, and arthritis was reported by 8.9% of marathoners. Arthritis prevalence was
8.8% for the subgroup of U.S. marathoners, significantly lower (p < 0.001) than
the prevalence in the matched U.S. population (17.9%) and in subgroups stratified
by age, sex, body mass index (BMI), and physical activity level (p < 0.001).
Seven marathoners continued to run following hip or knee arthroplasty. Age and
family and surgical history were independent risk factors for arthritis. There
was no significant risk associated with running duration, intensity, mileage, or
the number of marathons completed (p > 0.05). CONCLUSIONS: Age, family history,
and surgical history independently predicted an increased risk for hip and knee
arthritis in active marathoners, although there was no correlation with running
history. In our cohort, the arthritis rate of active marathoners was below that
of the general U.S. POPULATION: Longitudinal follow-up is needed to determine the
effects of marathon running on developing future hip and knee arthritis. LEVEL OF
EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete
description of levels of evidence.
PMID- 29342064
TI - Minimally Manipulated Bone Marrow Concentrate Compared with Microfracture
Treatment of Full-Thickness Chondral Defects: A One-Year Study in an Equine
Model.
AB - BACKGROUND: Microfracture is commonly performed for cartilage repair but usually
results in fibrocartilage. Microfracture augmented by autologous bone marrow
concentrate (BMC) was previously shown to yield structurally superior cartilage
repairs in an equine model compared with microfracture alone. The current study
was performed to test the hypothesis that autologous BMC without concomitant
microfracture improves cartilage repair compared with microfracture alone.
METHODS: Autologous sternal bone marrow aspirate (BMA) was concentrated using a
commercial system. Cells from BMC were evaluated for chondrogenic potential in
vitro and in vivo. Bilateral full-thickness chondral defects (15-mm diameter)
were created on the midlateral trochlear ridge in 8 horses. Paired defects were
randomly assigned to treatment with BMC without concomitant microfracture, or to
microfracture alone. The repairs were evaluated at 1 year by in vitro assessment,
arthroscopy, morphological magnetic resonance imaging (MRI), quantitative T2
weighted and ultrashort echo time enhanced T2* (UTE-T2*) MRI mapping, and
histological assessment. RESULTS: Culture-expanded but not freshly isolated cells
from BMA and BMC underwent cartilage differentiation in vitro. In vivo, cartilage
repairs in both groups were fibrous to fibrocartilaginous at 1 year of follow-up,
with no differences observed between BMC and microfracture by arthroscopy, T2 and
UTE-T2* MRI values, and histological assessment (p > 0.05). Morphological MRI
showed subchondral bone changes not observed by arthroscopy and improved overall
outcomes for the BMC repairs (p = 0.03). Differences in repair tissue UTE-T2*
texture features were observed between the treatment groups (p < 0.05).
CONCLUSIONS: When BMC was applied directly to critical-sized, full-thickness
chondral defects in an equine model, the cartilage repair results were similar to
those of microfracture. Our data suggest that, given the few mesenchymal stem
cells in minimally manipulated BMC, other mechanisms such as paracrine, anti
inflammatory, or immunomodulatory effects may have been responsible for tissue
regeneration in a previous study in which BMC was applied to microfractured
repairs. While our conclusions are limited by small numbers, the better MRI
outcomes for the BMC repairs may have been related to reduced surgical trauma to
the subchondral bone. CLINICAL RELEVANCE: MRI provides important information on
chondral defect subsurface repair organization and subchondral bone structure
that is not well assessed by arthroscopy.
PMID- 29342065
TI - Diagnosis of Periprosthetic Joint Infection: The Potential of Next-Generation
Sequencing.
AB - BACKGROUND: Next-generation sequencing is a well-established technique for
sequencing of DNA and has recently gained attention in many fields of medicine.
Our aim was to evaluate the accuracy of next-generation sequencing in identifying
the causative organism(s) in patients with periprosthetic joint infection.
METHODS: In this prospective study, samples were collected from 65 revision
arthroplasties (39 knees and 26 hips) and 17 primary arthroplasties (9 hips and 8
knees). Synovial fluid, deep tissue, and swabs were obtained at the time of the
surgical procedure and were shipped to the laboratory for next-generation
sequencing. Deep-tissue specimens were also sent to the institutional laboratory
for culture. Sensitivity and specificity were calculated for next-generation
sequencing, using the Musculoskeletal Infection Society (MSIS) definition of
periprosthetic joint infection as the standard. RESULTS: In 28 revisions, the
cases were considered to be infected; cultures were positive in 17 cases (60.7%
[95% confidence interval (CI), 40.6% to 78.5%]), and next-generation sequencing
was positive in 25 cases (89.3% [95% CI, 71.8% to 97.7%]), with concordance
between next-generation sequencing and culture in 15 cases. Among the 11 cases of
culture-negative periprosthetic joint infection, next-generation sequencing was
able to identify an organism in 9 cases (81.8% [95% CI, 48.2% to 97.7%]). Next
generation sequencing identified microbes in 9 (25.0% [95% CI, 12.1% to 42.2%])
of 36 aseptic revisions with negative cultures and in 6 (35.3% [95% CI, 14.2% to
61.7%]) of 17 primary total joint arthroplasties. Next-generation sequencing
detected several organisms in most positive samples. However, in the majority of
patients who were infected, 1 or 2 organisms were dominant. CONCLUSIONS: Next
generation sequencing may be a useful adjunct in identification of the causative
organism(s) in culture-negative periprosthetic joint infection. Our findings
suggest that some cases of monomicrobial periprosthetic joint infection may have
additional organisms that escape detection when culture is used. Further study is
required to determine the clinical implications of isolated organisms in samples
from patients who are not thought to be infected. LEVEL OF EVIDENCE: Diagnostic
Level I. See Instructions for Authors for a complete description of levels of
evidence.
PMID- 29342066
TI - Resident Participation in Fixation of Intertrochanteric Hip Fractures: Analysis
of the NSQIP Database.
AB - BACKGROUND: Future generations of orthopaedic surgeons must continue to be
trained in the surgical management of hip fractures. This study assesses the
effect of resident participation on outcomes for the treatment of
intertrochanteric hip fractures. METHODS: The National Surgical Quality
Improvement Program (NSQIP) database (2010 to 2013) was queried for
intertrochanteric hip fractures (International Classification of Diseases, 9th
Revision, Clinical Modification [ICD-9-CM] code 820.21) treated with either
extramedullary (Current Procedural Terminology [CPT] code 27244) or
intramedullary (CPT code 27245) fixation. Demographic variables, including
resident participation, as well as primary (death and serious morbidity) and
secondary outcome variables were extracted for analysis. Univariate, propensity
score-matched, and multivariate logistic regression analyses were performed to
evaluate outcome variables. RESULTS: Data on resident participation were
available for 1,764 cases (21.0%). Univariate analyses for all intertrochanteric
hip fractures demonstrated no significant difference in 30-day mortality (6.3%
versus 7.8%; p = 0.264) or serious morbidity (44.9% versus 43.2%; p = 0.506)
between the groups with and without resident participation. Multivariate and
propensity score-matched analyses gave similar results. Resident involvement was
associated with prolonged operating-room time, length of stay, and time to
discharge when a prolonged case was defined as one above the 90th percentile for
time parameters. CONCLUSIONS: Resident participation was not associated with an
increase in morbidity or mortality but was associated with an increase in time
related secondary outcome measures. While attending surgeon supervision is
necessary, residents can and should be involved in the care of these patients
without concern that resident involvement negatively impacts perioperative
morbidity and mortality. LEVEL OF EVIDENCE: Therapeutic Level III. See
Instructions for Authors for a complete description of levels of evidence.
PMID- 29342067
TI - There Is No Column: A New Classification for Acetabular Fractures.
AB - BACKGROUND: The surgical treatment of acetabular fractures relies on the
understanding of fracture architecture and their classification. The Judet and
Letournel classification has been the cornerstone in understanding and treating
acetabular fractures. Recently, there has been growing evidence of discrepancies
and incompleteness in the Judet and Letournel classification, adversely affecting
its clinical use. This study describes a novel comprehensive classification
system that will direct surgical approach and fixation methods. METHODS: A
retrospective study of patients with acetabular fractures treated at a level-I
trauma center also serving as a referral center for acetabular fractures was
performed. Fractures were classified according to both the novel and Judet and
Letournel classification systems. The novel classification developed integrates
the displacement vector (posterior, superomedial, or combined) and the fractured
anatomic structures (anteroposterior wall, pelvic brim, iliac wing, quadrilateral
plate, and ischium). Furthermore, postoperative malreduction was evaluated on the
basis of intra-articular gap measurements in either anteroposterior or Judet
oblique views. RESULTS: The study included 229 patients with acetabular fractures
treated between 2007 and 2016. The mean patient age (and standard deviation) was
46.7 +/- 21.75 years, and 172 patients (75.1%) were surgically treated. According
to the novel classification system, the posterior displacement vector group
included 60 patients, the superomedial displacement vector group included 130
patients, the combined displacement vector group included 36 patients, and 3
patients were unclassified by the new system. Forty-six patients (20.1%) could
not be classified by the Judet and Letournel classification. Pelvic-brim fracture
patterns were described as along the pelvic brim, across the pelvic brim, or
comminuted. The quadrilateral plate primary fracture line was shown to be
perpendicular to the pelvic brim. The selection of surgical approach and fixation
methods depends on the fracture type. CONCLUSIONS: This study presents a novel
classification system for acetabular fractures. It offers a complete
classification system, encompassing nearly all fracture patterns. As the
selection of surgical approach and fixation methods depends on fracture
classification and understanding, the novel classification system can aid the
surgeon with decision-making.
PMID- 29342068
TI - What's New in Adult Reconstructive Knee Surgery.
PMID- 29342069
TI - Orthopaedics in Haiti.
PMID- 29342070
TI - An Evaluation of Industry Relationships Among Contributors to AAOS Clinical
Practice Guidelines and Appropriate Use Criteria.
AB - BACKGROUND: A long-standing relationship between orthopaedic surgeons and
industry has made financial conflicts of interest a concerning issue. Research
supports that financial conflicts of interest can influence both medical research
and clinical practice. Financial conflicts of interest may also influence
clinical practice guideline recommendations and their corresponding appropriate
use criteria. Because of the influential nature of these guidelines, it is
imperative that care be taken to minimize bias during guideline development.
METHODS: We retrieved clinical practice guidelines and their corresponding
appropriate use criteria from the American Academy of Orthopaedic Surgery that
were published or revised between 2013 and 2016. We extracted industry payments
received by physicians using the Centers for Medicare & Medicaid Services Open
Payments database. We then evaluated the value and types of these payments. We
also used these data to determine whether disclosure statements were accurate and
whether guideline development was in adherence with the Institute of Medicine's
(IOM's) standards. RESULTS: Of the 106 physicians that were evaluated, 85 (80%)
received at least 1 industry payment, 56 (53%) accepted >$1,000, and 35 (33%)
accepted >$10,000. Financial payments amounted to a mean of $93,512 per
physician. Total reimbursement for the 85 clinical practice guideline and
appropriate use criteria contributors was $9,912,309. We found that disclosure
statements disagreed with the Open Payments data and that the IOM standards were
not completely enforced. CONCLUSIONS: Clinical practice guideline and appropriate
use criteria contributors received substantial payments from industry, many
disclosure statements were inaccurate, and the IOM standards were not completely
met. CLINICAL RELEVANCE: Clinical practice guidelines and appropriate use
criteria are critical for practicing evidence-based medicine. If financial
conflicts of interest are present during their development, it is possible that
patient care may be compromised.
PMID- 29342071
TI - Why We Should Care About the Sex of Specimens in Cadaveric, Animal, and Cell
Based Orthopaedic Research: Commentary on an article by Jessica Bryant, MD, et
al.: "Potential Sex Bias Exists in Orthopaedic Basic Science and Translational
Research".
PMID- 29342072
TI - Decreased Osteoarthritis Risk in Experienced Marathon Runners: Commentary on an
article by Danielle Y. Ponzio, MD, et al.: "Low Prevalence of Hip and Knee
Arthritis in Active Marathon Runners".
PMID- 29342073
TI - Structure Elucidation of Unknown Metabolites in Metabolomics by Combined NMR and
MS/MS Prediction.
AB - We introduce a cheminformatics approach that combines highly selective and
orthogonal structure elucidation parameters; accurate mass, MS/MS (MS2), and NMR
into a single analysis platform to accurately identify unknown metabolites in
untargeted studies. The approach starts with an unknown LC-MS feature, and then
combines the experimental MS/MS and NMR information of the unknown to effectively
filter out the false positive candidate structures based on their predicted MS/MS
and NMR spectra. We demonstrate the approach on a model mixture, and then we
identify an uncatalogued secondary metabolite in Arabidopsis thaliana. The
NMR/MS2 approach is well suited to the discovery of new metabolites in plant
extracts, microbes, soils, dissolved organic matter, food extracts, biofuels, and
biomedical samples, facilitating the identification of metabolites that are not
present in experimental NMR and MS metabolomics databases.
PMID- 29342074
TI - Characterization of an Additive Manufactured TiAl Alloy-Steel Joint Produced by
Electron Beam Welding.
AB - In this work, the characterization of the assembly of a steel shaft into a gamma
TiAl part for turbocharger application, obtained using Electron Beam Welding
(EBW) technology with a Ni-based filler, was carried out. The Ti-48Al-2Nb-0.7Cr
0.3Si (at %) alloy part was produced by Electron Beam Melting (EBM). This
additive manufacturing technology allows the production of a lightweight part
with complex shapes. The replacement of Nickel-based superalloys with TiAl alloys
in turbocharger automotive applications will lead to an improvement of the engine
performance and a substantial reduction in fuel consumption and emission. The
welding process allows a promising joint to be obtained, not affecting the TiAl
microstructure. Nevertheless, it causes the formation of diffusive layers between
the Ni-based filler and both steel and TiAl, with the latter side being
characterized by a very complex microstructure, which was fully characterized in
this paper by means of Scanning Electron Microscopy, Energy Dispersive X-ray
Spectroscopy, and nanoindentation. The diffusive interface has a thickness of
about 6 um, and it is composed of several layers. Specifically, from the TiAl
alloy side, we find a layer of Ti3Al followed by Al3NiTi2 and AlNi2Ti.
Subsequently Ni becomes more predominant, with a first layer characterized by
abundant carbide/boride precipitation, and a second layer characterized by Si
enrichment. Then, the chemical composition of the Ni-based filler is gradually
reached.
PMID- 29342075
TI - Enrichment and Identification of the Most Abundant Zinc Binding Proteins in
Developing Barley Grains by Zinc-IMAC Capture and Nano LC-MS/MS.
AB - Background: Zinc accumulates in the embryo, aleurone, and subaleurone layers at
different amounts in cereal grains. Our hypothesis is that zinc could be stored
bound, not only to low MW metabolites/proteins, but also to high MW proteins as
well. Methods: In order to identify the most abundant zinc binding proteins in
different grain tissues, we microdissected barley grains into (1) seed coats; (2)
aleurone/subaleurone; (3) embryo; and (4) endosperm. Initial screening for
putative zinc binding proteins from the different tissue types was performed by
fractionating proteins according to solubility (Osborne fractionation), and
resolving those via Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis
(SDS-PAGE) followed by polyvinylidene fluoride (PVDF) membrane blotting and
dithizone staining. Selected protein fractions were subjected to Zn2+-immobilized
metal ion affinity chromatography, and the captured proteins were identified
using nanoscale liquid chromatography coupled to tandem mass spectrometry (nanoLC
MS/MS). Results: In the endosperm, the most abundant zinc binding proteins were
the storage protein B-hordeins, gamma-, and D-hordeins, while in the embryo, 7S
globulins storage proteins exhibited zinc binding. In the aleurone/subaleurone,
zinc affinity captured proteins were late abundant embryogenesis proteins,
dehydrins, many isoforms of non-specific lipid transfer proteins, and alpha
amylase trypsin inhibitor. Conclusions: We have shown evidence that abundant
barley grain proteins have been captured by Zn-IMAC, and their zinc binding
properties in relationship to the possibility of zinc storage is discussed.
PMID- 29342076
TI - Neuromorphic Vibrotactile Stimulation of Fingertips for Encoding Object Stiffness
in Telepresence Sensory Substitution and Augmentation Applications.
AB - We present a tactile telepresence system for real-time transmission of
information about object stiffness to the human fingertips. Experimental tests
were performed across two laboratories (Italy and Ireland). In the Italian
laboratory, a mechatronic sensing platform indented different rubber samples.
Information about rubber stiffness was converted into on-off events using a
neuronal spiking model and sent to a vibrotactile glove in the Irish laboratory.
Participants discriminated the variation of the stiffness of stimuli according to
a two-alternative forced choice protocol. Stiffness discrimination was based on
the variation of the temporal pattern of spikes generated during the indentation
of the rubber samples. The results suggest that vibrotactile stimulation can
effectively simulate surface stiffness when using neuronal spiking models to
trigger vibrations in the haptic interface. Specifically, fractional variations
of stiffness down to 0.67 were significantly discriminated with the developed
neuromorphic haptic interface. This is a performance comparable, though slightly
worse, to the threshold obtained in a benchmark experiment evaluating the same
set of stimuli naturally with the own hand. Our paper presents a bioinspired
method for delivering sensory feedback about object properties to human skin
based on contingency-mimetic neuronal models, and can be useful for the design of
high performance haptic devices.
PMID- 29342077
TI - Use of a New International Classification of Health Interventions for Capturing
Information on Health Interventions Relevant to People with Disabilities.
AB - Development of the World Health Organization's International Classification of
Health Interventions (ICHI) is currently underway. Once finalised, ICHI will
provide a standard basis for collecting, aggregating, analysing, and comparing
data on health interventions across all sectors of the health system. In this
paper, we introduce the classification, describing its underlying tri-axial
structure, organisation and content. We then discuss the potential value of ICHI
for capturing information on met and unmet need for health interventions relevant
to people with a disability, with a particular focus on interventions to support
functioning and health promotion interventions. Early experiences of use of the
Swedish National Classification of Social Care Interventions and Activities,
which is based closely on ICHI, illustrate the value of a standard classification
to support practice and collect statistical data. Testing of the ICHI beta
version in a wide range of countries and contexts is now needed so that
improvements can be made before it is finalised. Input from those with an
interest in the health of people with disabilities and health promotion more
broadly is welcomed.
PMID- 29342078
TI - Spin Absorption Effect at Ferromagnet/Ge Schottky-Tunnel Contacts.
AB - We study the influence of the junction size in ferromagnet (FM)/semiconductor
(SC) contacts on four-terminal nonlocal spin signals in SC-based lateral spin
valve (LSV) structures. When we use FM/Ge Schottky-tunnel junctions with
relatively low resistance-area products, the magnitude of the nonlocal spin
signal depends clearly on the junction size, indicating the presence of the spin
absorption effect at the spin-injector contact. The temperature-dependent spin
signal can also be affected by the spin absorption effect. For SC spintronic
applications with a low parasitic resistance, we should consider the influence of
the spin absorption on the spin-transport signals in SC-based device structures.
PMID- 29342079
TI - Selective Laser Melting Produced Ti-6Al-4V: Post-Process Heat Treatments to
Achieve Superior Tensile Properties.
AB - Current post-process heat treatments applied to selective laser melting produced
Ti-6Al-4V do not achieve the same microstructure and therefore superior tensile
behaviour of thermomechanical processed wrought Ti-6Al-4V. Due to the growing
demand for selective laser melting produced parts in industry, research and
development towards improved mechanical properties is ongoing. This study is
aimed at developing post-process annealing strategies to improve tensile
behaviour of selective laser melting produced Ti-6Al-4V parts. Optical and
electron microscopy was used to study alpha grain morphology as a function of
annealing temperature, hold time and cooling rate. Quasi-static uniaxial tensile
tests were used to measure tensile behaviour of different annealed parts. It was
found that elongated alpha'/alpha grains can be fragmented into equiaxial grains
through applying a high temperature annealing strategy. It is shown that bi-modal
microstructures achieve a superior tensile ductility to current heat treated
selective laser melting produced Ti-6Al-4V samples.
PMID- 29342080
TI - Comparisons of Different Models on Dynamic Recrystallization of Plate during
Asymmetrical Shear Rolling.
AB - Asymmetrical shear rolling with velocity asymmetry and geometry asymmetry is
beneficial to enlarge deformation and refine grain size at the center of the
thick plate compared to conventional symmetrical rolling. Dynamic
recrystallization (DRX) plays a vital role in grain refinement during hot
deformation. Finite element models (FEM) coupled with microstructure evolution
models and cellular automata models (CA) are established to study the
microstructure evolution of plate during asymmetrical shear rolling. The results
show that a larger DRX fraction and a smaller average grain size can be obtained
at the lower layer of the plate. The DRX fraction at the lower part increases
with the ascending speed ratio, while that at upper part decreases. With the
increase of the offset distance, the DRX fraction slightly decreases for the
whole thickness of the plate. The differences in the DRX fraction and average
grain size between the upper and lower surfaces increase with the ascending speed
ratio; however, it varies little with the change of the speed ratio. Experiments
are conducted and the CA models have a higher accuracy than FEM models as the
grain morphology, DRX nuclei, and grain growth are taken into consideration in CA
models, which are more similar to the actual DRX process during hot deformation.
PMID- 29342081
TI - Age and Gender Differences in Psychological Distress among African Americans and
Whites: Findings from the 2016 National Health Interview Survey.
AB - Previous studies report a race and mental health paradox: Whites score higher on
measures of major depression compared to African Americans, but the opposite is
true for psychological distress (i.e., African Americans score higher on distress
measures compared to Whites). Independently, race, age, and gender outcomes for
psychological distress are well documented in the literature. However, there is
relatively little research on how psychological distress interferes with the
lives of African Americans and Whites at the intersection of their various race,
age, and gender identities. This study uses data from the 2016 National Health
Interview Survey to examine age and gender differences in psychological distress
and how much psychological distress interferes with the lives of African
Americans and Whites. Our study findings are contrary to the paradox such that
young White women (M = 3.36, SD = 1.14) and middle-aged White men (M = 2.55, SD =
3.97) experienced higher psychological distress than all other race, age, and
gender groups. Psychological distress interference was relatively high among the
high distress groups, except for older African American men (M = 1.73, SD = 1.05)
and young African American women (M = 1.93, SD = 0.95). Implications for studies
that consider cultural experiences of psychological distress, and how it impacts
different demographic groups are discussed.
PMID- 29342082
TI - Lewis Pair Catalysts in the Polymerization of Lactide and Related Cyclic Esters.
AB - Polyesters, especially poly(lactide) (PLA), are used widely as biodegradable and
biocompatible materials, yet their controllable synthesis, especially the
stereoselective synthesis of polyesters, is still a challenge. Recently some
excellent Lewis pair catalysts for ring-opening polymerization (ROP) of lactide
and related cyclic esters have emerged. This review article will highlight the
key advances in the ROP catalyzed by Lewis pair compounds with the aim of
encouraging the wider application of Lewis pair catalysts in the polymerization
of lactide and related cyclic esters.
PMID- 29342083
TI - Regulation of Mitochondrial Dynamics by Proteolytic Processing and Protein
Turnover.
AB - The mitochondrial network is a dynamic organization within eukaryotic cells that
participates in a variety of essential cellular processes, such as adenosine
triphosphate (ATP) synthesis, central metabolism, apoptosis and inflammation. The
mitochondrial network is balanced between rates of fusion and fission that
respond to pathophysiologic signals to coordinate appropriate mitochondrial
processes. Mitochondrial fusion and fission are regulated by proteins that either
reside in or translocate to the inner or outer mitochondrial membranes or are
soluble in the inter-membrane space. Mitochondrial fission and fusion are
performed by guanosine triphosphatases (GTPases) on the outer and inner
mitochondrial membranes with the assistance of other mitochondrial proteins. Due
to the essential nature of mitochondrial function for cellular homeostasis,
regulation of mitochondrial dynamics is under strict control. Some of the
mechanisms used to regulate the function of these proteins are post-translational
proteolysis and/or turnover, and this review will discuss these mechanisms
required for correct mitochondrial network organization.
PMID- 29342085
TI - Development of a Region-Specific Physiologically Based Pharmacokinetic Brain
Model to Assess Hippocampus and Frontal Cortex Pharmacokinetics.
AB - Central nervous system drug discovery and development is hindered by the
impermeable nature of the blood-brain barrier. Pharmacokinetic modeling can
provide a novel approach to estimate CNS drug exposure; however, existing models
do not predict temporal drug concentrations in distinct brain regions. A rat CNS
physiologically based pharmacokinetic (PBPK) model was developed, incorporating
brain compartments for the frontal cortex (FC), hippocampus (HC), "rest-of-brain"
(ROB), and cerebrospinal fluid (CSF). Model predictions of FC and HC Cmax, tmax
and AUC were within 2-fold of that reported for carbamazepine and phenytoin. The
inclusion of a 30% coefficient of variation on regional brain tissue volumes, to
assess the uncertainty of regional brain compartments volumes on predicted
concentrations, resulted in a minimal level of sensitivity of model predictions.
This model was subsequently extended to predict human brain morphine
concentrations, and predicted a ROB Cmax of 21.7 +/- 6.41 ng/mL when compared to
"better" (10.1 ng/mL) or "worse" (29.8 ng/mL) brain tissue regions with a FC Cmax
of 62.12 +/- 17.32 ng/mL and a HC Cmax of 182.2 +/- 51.2 ng/mL. These results
indicate that this simplified regional brain PBPK model is useful for forward
prediction approaches in humans for estimating regional brain drug
concentrations.
PMID- 29342086
TI - Copy Number Variation in SOX6 Contributes to Chicken Muscle Development.
AB - Copy number variations (CNVs), which cover many functional genes, are associated
with complex diseases, phenotypic diversity and traits that are economically
important to raising chickens. The sex-determining region Y-box 6 (Sox6) plays a
key role in fast-twitch muscle fiber differentiation of zebrafish and mice, but
it is still unknown whether SOX6 plays a role in chicken skeletal muscle
development. We identified two copy number polymorphisms (CNPs) which were
significantly related to different traits on the genome level in chickens by
AccuCopy(r) and CNVplex(r) analyses. Notably, five white recessive rock (CN = 1,
CN = 3) variant individuals and two Xinghua (CN = 3) variant individuals contain
a CNP13 (chromosome5: 10,500,294-10,675,531) which overlaps with SOX6. There is a
disordered region in SOX6 proteins 265-579 aa coded by a partial CNV overlapping
region. A quantitative real-time polymerase chain reaction showed that the
expression level of SOX6 mRNA was positively associated with CNV and highly
expressed during the skeletal muscle cell differentiation in chickens. After the
knockdown of the SOX6, the expression levels of IGFIR1, MYF6, SOX9, SHOX and
CCND1 were significantly down-regulated. All of them directly linked to muscle
development. These results suggest that the number of CNVs in the CNP13 is
positively associated with the expression level of SOX6, which promotes the
proliferation and differentiation of skeletal muscle cells by up-regulating the
expression levels of the muscle-growth-related genes in chickens as in other
animal species.
PMID- 29342088
TI - Synthesis and Characterization of WO3/Graphene Nanocomposites for Enhanced
Photocatalytic Activities by One-Step In-Situ Hydrothermal Reaction.
AB - Tungsten trioxide (WO3) nanorods are synthesized on the surface of graphene (GR)
sheets by using a one-step in-situ hydrothermal method employing sodium tungstate
(Na2WO4.2H2O) and graphene oxide (GO) as precursors. The resulting WO3/GR
nanocomposites are characterized by X-ray diffraction, Raman spectroscopy,
transmission electron microscopy, scanning electron microscopy and X-ray
photoelectron spectroscopy. The results confirm that the interface between WO3
nanorod and graphene contains chemical bonds. The enhanced optical absorption
properties are measured by UV-vis diffuse reflectance spectra. The photocatalytic
activity of the WO3/GR nanocomposites under visible light is evaluated by the
photodegradation of methylene blue, where the degradation rate of WO3/GR
nanocomposites is shown to be double that of pure WO3. This is attributed to the
synergistic effect of graphene and the WO3 nanorod, which greatly enhances the
photocatalytic performance of the prepared sample, reduces the recombination of
the photogenerated electron-hole pairs and increases the visible light absorption
efficiency. Finally, the photocatalytic mechanism of the WO3/GR nanocomposites is
presented. The synthesis of the prepared sample is convenient, direct and
environmentally friendly. The study reports a highly efficient composite
photocatalyst for the degradation of contaminants that can be applied to cleaning
up the environment.
PMID- 29342087
TI - Sophisticated Fowl: The Complex Behaviour and Cognitive Skills of Chickens and
Red Junglefowl.
AB - The world's most numerous bird, the domestic chicken, and their wild ancestor,
the red junglefowl, have long been used as model species for animal behaviour
research. Recently, this research has advanced our understanding of the social
behaviour, personality, and cognition of fowl, and demonstrated their
sophisticated behaviour and cognitive skills. Here, we overview some of this
research, starting with describing research investigating the well-developed
senses of fowl, before presenting how socially and cognitively complex they can
be. The realisation that domestic chickens, our most abundant production animal,
are behaviourally and cognitively sophisticated should encourage an increase in
general appraise and fascination towards them. In turn, this should inspire
increased use of them as both research and hobby animals, as well as improvements
in their unfortunately often poor welfare.
PMID- 29342089
TI - Chitosan Gel to Treat Pressure Ulcers: A Clinical Pilot Study.
AB - Chitosan is biopolymer with promising properties in wound healing. Chronic wounds
represent a significant burden to both the patient and the medical system. Among
chronic wounds, pressure ulcers are one of the most common types of complex
wound. The efficacy and the tolerability of chitosan gel formulation, prepared
into the hospital pharmacy, in the treatment of pressure ulcers of moderate
severity were evaluated. The endpoint of this phase II study was the reduction of
the area of the lesion by at least 20% after four weeks of treatment. Thus, 20
adult volunteers with pressure ulcers within predetermined parameters were
involved in a 30 days study. Dressing change was performed twice a week at
outpatient clinic upon chronic wounds management. In the 90% of patients involved
in the study, the treatment was effective, with a reduction of the area of the
lesion and wound healing progress. The study demonstrated the efficacy of the gel
formulation for treatment of pressure ulcers, also providing a strong reduction
of patient management costs.
PMID- 29342090
TI - Development of Databases on Iodine in Foods and Dietary Supplements.
AB - Iodine is an essential micronutrient required for normal growth and
neurodevelopment; thus, an adequate intake of iodine is particularly important
for pregnant and lactating women, and throughout childhood. Low levels of iodine
in the soil and groundwater are common in many parts of the world, often leading
to diets that are low in iodine. Widespread salt iodization has eradicated severe
iodine deficiency, but mild-to-moderate deficiency is still prevalent even in
many developed countries. To understand patterns of iodine intake and to develop
strategies for improving intake, it is important to characterize all sources of
dietary iodine, and national databases on the iodine content of major dietary
contributors (including foods, beverages, water, salts, and supplements) provide
a key information resource. This paper discusses the importance of well
constructed databases on the iodine content of foods, beverages, and dietary
supplements; the availability of iodine databases worldwide; and factors related
to variability in iodine content that should be considered when developing such
databases. We also describe current efforts in iodine database development in the
United States, the use of iodine composition data to develop food fortification
policies in New Zealand, and how iodine content databases might be used when
considering the iodine intake and status of individuals and populations.
PMID- 29342091
TI - DNA-Based Single-Molecule Electronics: From Concept to Function.
AB - Beyond being the repository of genetic information, DNA is playing an
increasingly important role as a building block for molecular electronics. Its
inherent structural and molecular recognition properties render it a leading
candidate for molecular electronics applications. The structural stability,
diversity and programmability of DNA provide overwhelming freedom for the design
and fabrication of molecular-scale devices. In the past two decades DNA has
therefore attracted inordinate amounts of attention in molecular electronics.
This review gives a brief survey of recent experimental progress in DNA-based
single-molecule electronics with special focus on single-molecule conductance and
I-V characteristics of individual DNA molecules. Existing challenges and exciting
future opportunities are also discussed.
PMID- 29342093
TI - Hydroxyl Ion Diffusion through Radicular Dentine When Calcium Hydroxide Is Used
under Different Conditions.
AB - Calcium hydroxide's anti-bacterial action relies on high pH. The aim here was to
investigate hydroxyl ion diffusion through dentine under different conditions.
Teeth were divided into control (n = 4) and four experimental groups (n = 10):
Group 1-no medicament; Group 2-Calmix; Group 3-Calmix/Ledermix; Group 4-Calasept
Plus/Ledermix; Group 5-Pulpdent/smear layer. Deep (inner dentine) and shallow
(outer dentine) cavities were cut into each root. pH was measured in these
cavities for 12 weeks. The inner and outer dentine pH in Group 2 was
significantly higher than all groups. Inner dentine pH in Group 3 was slightly
higher than that in Group 4 initially but subsequently comparable. After Day 2,
Group 5 had significantly lower pH than Groups 3 and 4. The outer dentine pH in
Group 3 started higher than that in Groups 4 and 5, but by Day 28 the difference
was insignificant. The time for the inner dentine to reach maximum pH was one
week for Group 2 and four weeks for Groups 3 and 4. The time for the outer
dentine to reach maximum pH was eight weeks for all experimental groups. Mixing
different Ca(OH)2 formulations with Ledermix gave similar hydroxyl ion release
but pH and total diffusion was lower than Ca(OH)2 alone. The smear layer
inhibited diffusion.
PMID- 29342092
TI - Metabolic Alterations in Cancer Cells and the Emerging Role of Oncometabolites as
Drivers of Neoplastic Change.
AB - The mitochondrion is an important organelle and provides energy for a plethora of
intracellular reactions. Metabolic dysregulation has dire consequences for the
cell, and alteration in metabolism has been identified in multiple disease states
cancer being one. Otto Warburg demonstrated that cancer cells, in the presence of
oxygen, undergo glycolysis by reprogramming their metabolism-termed "aerobic
glycolysis". Alterations in metabolism enable cancer cells to gain a growth
advantage by obtaining precursors for macromolecule biosynthesis, such as nucleic
acids and lipids. To date, several molecules, termed "oncometabolites", have been
identified to be elevated in cancer cells and arise from mutations in nuclear
encoded mitochondrial enzymes. Furthermore, there is evidence that
oncometabolites can affect mitochondrial dynamics. It is believed that
oncometabolites can assist in reprogramming enzymatic pathways and providing
cancer cells with selective advantages. In this review, we will touch upon the
effects of normal and aberrant mitochondrial metabolism in normal and cancer
cells, the advantages of metabolic reprogramming, effects of oncometabolites on
metabolism and mitochondrial dynamics and therapies aimed at targeting
oncometabolites and metabolic aberrations.
PMID- 29342094
TI - Telomeric Repeat-Containing RNAs (TERRA) Decrease in Squamous Cell Carcinoma of
the Head and Neck Is Associated with Worsened Clinical Outcome.
AB - Telomeres are transcribed into noncoding telomeric repeat-containing RNAs
(TERRA), which are essential for telomere maintenance. Deregulation of TERRA
transcription impairs telomere metabolism and a role in tumorigenesis has been
proposed. Head and neck cancer (HNC) is one of the most frequent cancers
worldwide, with head and neck squamous cell carcinoma (HNSCC) being the
predominant type. Since HNSCC patients are characterized by altered telomere
maintenance, a dysfunction in telomere transcription can be hypothesized. In this
prospective study, we compared TERRA levels in the tumor and matched normal
tissue from 23 HNSCC patients. We then classified patients in two categories
according to the level of TERRA expression in the tumor compared to the normal
tissue: (1) lower expression in the tumor, (2) higher or similar expression in
tumor. A significant proportion of patients in the first group died of the
disease within less than 34 months postsurgery, while the majority of patients in
the second group were alive and disease-free. Our results highlight a striking
correlation between TERRA expression and tumor aggressiveness in HNSCC suggesting
that TERRA levels may be proposed as a novel molecular prognostic marker for
HNSCC.
PMID- 29342095
TI - Preparation of Cyano-Substituted Tetraphenylethylene Derivatives and Their
Applications in Solution-Processable OLEDs.
AB - Creation of organic luminescent materials with high solid-state efficiency is of
vital importance for their applications in optoelectronic fields. Here, a series
of AIE luminogens (AIE gens), (Z)-2,3-bis(4-(9,9-bis(6-(9H-carbazol-9-yl)hexyl)
9H-fluoren-2-yl)phenyl)-3-phenylacrylonitrile (SFC), and 2,3-bis(4-(9,9-bis(6-(9H
carbazol-9-yl)hexyl)-9H-fluoren-2-yl)phenyl)fumaronitrile (DFC), utilizing 2,3,3
triphenylacrylonitrile and 2,3-diphenylfumaronitrile as respective centers, are
designed and synthesized by Suzuki coupling reactions with high yields. The cis-
and trans-isomers of DFC are also successfully obtained. All of them are
thermally stable and show good solubility in common organic solvents. They all
emit weakly in solution, but become strong emitters when fabricated into solid
films. It is found introduction of one additional cyano group in DFC induced a
big red-shift in solid-state emission, owing to its high electron-withdrawing
ability. The cis- and trans-DFC show similar photophysical and Cyclic
voltammogram (CV) behaviors. Non-doped solution-processed organic light-emitting
diodes (OLEDs) using the three compounds as light-emitting layers are fabricated.
SFC gives the best device performance with a maximum luminance of 5201 cd m-2, a
maximum current efficiency of 3.67 cd A-1 and a maximum external quantum
efficiencies (EQE) of 1.37%. Red-shifted EL spectra are observed for cis- and
trans-DFC-based device, and the OLED using trans-DFC as active layer exhibits
better performance, which might derive from their different conformation in film
state.
PMID- 29342096
TI - High-Resolution Lipidomics of the Early Life Stages of the Red Seaweed Porphyra
dioica.
AB - Porphyra dioica is a commercial seaweed consumed all over the world, mostly in
the shape of nori sheets used for "sushi" preparation. It is a well-known part of
the Asian diet with health benefits, which have been associated, among others, to
the high levels of n-3 and n-6 fatty acids in this red alga. However, other
highly valued lipids of Porphyra are polar lipids that remain largely undescribed
and can have both nutritional value and bioactivity, thus could contribute to the
valorization of this seaweed. In this context, the present work aims to identify
the lipidome of two life cycle stages of the Atlantic species Porphyra dioica:
the early life stage conchocelis produced in an indoor-nursery, and young blades
produced outdoors using an integrated multitrophic aquaculture (IMTA) framework.
Both the blades (gametophyte) and conchocelis (sporophyte) are commercialized in
the food and cosmetics sectors. Liquid chromatography coupled to Q-Exactive high
resolution-mass spectrometry (MS) platform was used to gain insight into the
lipidome of these species. Our results allowed the identification of 110 and 100
lipid molecular species in the lipidome of the blade and conchocelis,
respectively. These lipid molecular species were distributed as follows
(blade/conchocelis): 14/15 glycolipids (GLs), 93/79 phospholipids (PLs), and 3/6
betaine lipids. Both life stages displayed a similar profile of GLs and comprised
20:4(n-6) and 20:5(n-3) fatty acids that contribute to n-3 and n-6 fatty acid
pool recorded and rank among the molecular species with higher potential
bioactivity. PLs' profile was different between the two life stages surveyed,
mainly due to the number and relative abundance of molecular species. This
finding suggests that differences between both life stages were more likely
related with shifts in the lipids of extraplastidial membranes rather than in
plastidial membranes. PLs contained n-6 and n-3 precursors and in both life
stages of Porphyra dioica the n-6/n-3 ratio recorded was less than 2,
highlighting the potential benefits of using these life stages in human diet to
prevent chronic diseases. Atherogenic and thrombogenic indexes of blades (0.85
and 0.49, respectively) and conchocelis (0.34 and 0.30, respectively) are much
lower than those reported for other Rhodophyta, which highlights their potential
application as food or as functional ingredients. Overall, MS-based platforms
represent a powerful tool to characterize lipid metabolism and target lipids
along different life stages of algal species displaying complex life cycles (such
as Porphyra dioica), contributing to their biotechnological application.
PMID- 29342097
TI - Time Domain Near Infrared Spectroscopy Device for Monitoring Muscle Oxidative
Metabolism: Custom Probe and In Vivo Applications.
AB - Measurement of muscle oxidative metabolism is of interest for monitoring the
training status in athletes and the rehabilitation process in patients. Time
domain near infrared spectroscopy (TD NIRS) is an optical technique that allows
the non-invasive measurement of the hemodynamic parameters in muscular tissue:
concentrations of oxy- and deoxy-hemoglobin, total hemoglobin content, and tissue
oxygen saturation. In this paper, we present a novel TD NIRS medical device for
muscle oxidative metabolism. A custom-printed 3D probe, able to host optical
elements for signal acquisition from muscle, was develop for TD NIRS in vivo
measurements. The system was widely characterized on solid phantoms and during in
vivo protocols on healthy subjects. In particular, we tested the in vivo
repeatability of the measurements to quantify the error that we can have by
repositioning the probe. Furthermore, we considered a series of acquisitions on
different muscles that were not yet previously performed with this custom probe:
a venous-arterial cuff occlusion of the arm muscle, a cycling exercise, and an
isometric contraction of the vastus lateralis.
PMID- 29342098
TI - Mechano-Enzymatic Deconstruction with a New Enzymatic Cocktail to Enhance
Enzymatic Hydrolysis and Bioethanol Fermentation of Two Macroalgae Species.
AB - The aim of this study was to explore the efficiency of a mechano-enzymatic
deconstruction of two macroalgae species for sugars and bioethanol production, by
using a new enzymatic cocktail (Haliatase) and two types of milling modes (vibro
ball: VBM and centrifugal milling: CM). By increasing the enzymatic concentration
from 3.4 to 30 g/L, the total sugars released after 72 h of hydrolysis increased
(from 6.7 to 13.1 g/100 g TS and from 7.95 to 10.8 g/100 g TS for the green algae
U. lactuca and the red algae G. sesquipedale, respectively). Conversely, total
sugars released from G. sesquipedale increased (up to 126% and 129% after VBM and
CM, respectively). The best bioethanol yield (6 geth/100 g TS) was reached after
72 h of fermentation of U. lactuca and no increase was obtained after centrifugal
milling. The latter led to an enhancement of the ethanol yield of G. sesquipedale
(from 2 to 4 g/100 g TS).
PMID- 29342099
TI - Poly(lactic acid) (PLA) Based Tear Resistant and Biodegradable Flexible Films by
Blown Film Extrusion.
AB - Poly(lactic acid) (PLA) was melt mixed in a laboratory extruder with
poly(butylene adipate-co-terephthalate) (PBAT) and poly(butylene succinate) (PBS)
in the presence of polypropylene glycol di glycidyl ether (EJ400) that acted as
both plasticizer and compatibilizer. The process was then scaled up in a semi
industrial extruder preparing pellets having different content of a nucleating
agent (LAK). All of the formulations could be processed by blowing extrusion and
the obtained films showed mechanical properties dependent on the LAK content. In
particular the tearing strength showed a maximum like trend in the investigated
composition range. The films prepared with both kinds of blends showed a tensile
strength in the range 12-24 MPa, an elongation at break in the range 150-260% and
a significant crystallinity.
PMID- 29342101
TI - A Novel Methodology for Improving Plant Pest Surveillance in Vineyards and Crops
Using UAV-Based Hyperspectral and Spatial Data.
AB - Recent advances in remote sensed imagery and geospatial image processing using
unmanned aerial vehicles (UAVs) have enabled the rapid and ongoing development of
monitoring tools for crop management and the detection/surveillance of insect
pests. This paper describes a (UAV) remote sensing-based methodology to increase
the efficiency of existing surveillance practices (human inspectors and insect
traps) for detecting pest infestations (e.g., grape phylloxera in vineyards). The
methodology uses a UAV integrated with advanced digital hyperspectral,
multispectral, and RGB sensors. We implemented the methodology for the
development of a predictive model for phylloxera detection. In this method, we
explore the combination of airborne RGB, multispectral, and hyperspectral imagery
with ground-based data at two separate time periods and under different levels of
phylloxera infestation. We describe the technology used-the sensors, the UAV, and
the flight operations-the processing workflow of the datasets from each imagery
type, and the methods for combining multiple airborne with ground-based datasets.
Finally, we present relevant results of correlation between the different
processed datasets. The objective of this research is to develop a novel
methodology for collecting, processing, analising and integrating multispectral,
hyperspectral, ground and spatial data to remote sense different variables in
different applications, such as, in this case, plant pest surveillance. The
development of such methodology would provide researchers, agronomists, and UAV
practitioners reliable data collection protocols and methods to achieve faster
processing techniques and integrate multiple sources of data in diverse remote
sensing applications.
PMID- 29342100
TI - Modulation of the Fungal-Host Interaction by the Intra-Species Diversity of C.
albicans.
AB - The incidence of human infections caused by the opportunistic fungal pathogen
Candida albicans is on the rise due to increasing numbers of immunosuppressed
patients. The importance of the immune system in preventing overgrowth of the
colonizing fungus and thereby limiting infection is well recognized and host
protective mechanisms widely investigated. Only recently, it was recognized that
the natural diversity in the fungal species could also influence the outcome of
the interaction between the fungus and the host. C. albicans strain-specific
differences are complex and their regulation at the genomic, genetic, and
epigenetic level and by environmental factors is only partially understood. In
this review, we provide an overview of the natural diversity of C. albicans and
discuss how it impacts host-fungal interactions and thereby affects the balance
between commensalism versus disease.
PMID- 29342102
TI - Development of a High-Sensitivity Wireless Accelerometer for Structural Health
Monitoring.
AB - Structural health monitoring (SHM) is playing an increasingly important role in
ensuring the safety of structures. A shift of SHM research away from traditional
wired methods toward the use of wireless smart sensors (WSS) has been motivated
by the attractive features of wireless smart sensor networks (WSSN). The progress
achieved in Micro Electro-Mechanical System (MEMS) technologies and wireless data
transmission, has extended the effectiveness and range of applicability of WSSNs.
One of the most common sensors employed in SHM strategies is the accelerometer;
however, most accelerometers in WSS nodes have inadequate resolution for
measurement of the typical accelerations found in many SHM applications. In this
study, a high-resolution and low-noise tri-axial digital MEMS accelerometer is
incorporated in a next-generation WSS platform, the Xnode. In addition to meeting
the acceleration sensing demands of large-scale civil infrastructure
applications, this new WSS node provides powerful hardware and a robust software
framework to enable edge computing that can deliver actionable information.
Hardware and software integration challenges are presented, and the associate
resolutions are discussed. The performance of the wireless accelerometer is
demonstrated experimentally through comparison with high-sensitivity wired
accelerometers. This new high-sensitivity wireless accelerometer will extend the
use of WSSN to a broader class of SHM applications.
PMID- 29342103
TI - Minimally-Invasive Neural Interface for Distributed Wireless Electrocorticogram
Recording Systems.
AB - This paper presents a minimally-invasive neural interface for distributed
wireless electrocorticogram (ECoG) recording systems. The proposed interface
equips all necessary components for ECoG recording, such as the high performance
front-end integrated circuits, a fabricated flexible microelectrode array, and
wireless communication inside a miniaturized custom-made platform. The multiple
units of the interface systems can be deployed to cover a broad range of the
target brain region and transmit signals via a built-in intra-skin communication
(ISCOM) module. The core integrated circuit (IC) consists of 16-channel, low
power push-pull double-gated preamplifiers, in-channel successive approximation
register analog-to-digital converters (SAR ADC) with a single-clocked
bootstrapping switch and a time-delayed control unit, an ISCOM module for
wireless data transfer through the skin instead of a power-hungry RF wireless
transmitter, and a monolithic voltage/current reference generator to support the
aforementioned analog and mixed-signal circuit blocks. The IC was fabricated
using 250 nm CMOS processes in an area of 3.2 * 0.9 mm2 and achieved the low
power operation of 2.5 uW per channel. Input-referred noise was measured as 5.62
uVrms for 10 Hz to 10 kHz and ENOB of 7.21 at 31.25 kS/s. The implemented system
successfully recorded multi-channel neural activities in vivo from a primate and
demonstrated modular expandability using the ISCOM with power consumption of 160
uW.
PMID- 29342104
TI - Synthesis, Anti-Proliferative Activity Evaluation and 3D-QSAR Study of
Naphthoquinone Derivatives as Potential Anti-Colorectal Cancer Agents.
AB - Colorectal cancer (CRC) is a disease with high incidence and mortality,
constituting the fourth most common cause of death from cancer worldwide.
Naphthoquinones are attractive compounds due to their biological and structural
properties. In this work, 36 naphthoquinone derivatives were synthesized and
their activity evaluated against HT-29 cells. Overall, high to moderate anti
proliferative activity was observed in most members of the series, with 15
compounds classified as active (1.73 < IC50 < 18.11 MUM). The naphtho[2,3
b]thiophene-4,9-dione analogs showed potent cytotoxicity, 8-hydroxy-2-(thiophen-2
ylcarbonyl)naphtho[2,3-b]thiophene-4,9-dione being the compound with the highest
potency and selectivity. Our results suggest that the toxicity is improved in
molecules with tricyclic naphtho[2,3-b]furan-4,9-dione and naphtho[2,3
b]thiophene-4,9-dione systems 2-substituted with an electron-withdrawing group. A
3D-QSAR study of comparative molecular field analysis (CoMFA) was carried out,
resulting in the generation of a reliable model (r2 = 0.99 and q2 = 0.625). This
model allowed proposing five new compounds with two-fold higher theoretical anti
proliferative activity, which would be worthwhile to synthesize and evaluate.
Further investigations will be needed to determine the mechanism involved in the
effect of most active compounds which are potential candidates for new anticancer
agents.
PMID- 29342105
TI - Neuroimmune-Driven Neuropathic Pain Establishment: A Focus on Gender Differences.
AB - The role of neuroinflammatory cells in the establishment of neuropathic pain has
been investigated in depth in the last few years. In particular, microglia have
been shown to be key players in the induction of tactile allodynia, as they
release proinflammatory molecules that, in turn, sensitize nociceptive neurons
within the spinal cord. However, the role of peripheral immune cells such as
macrophages, infiltrating monocytes, mast cells, and T-cells has been highlighted
in the last few studies, even though the data are still conflicting and need to
be clarified. Intriguingly, the central (microglia) and peripheral (T-cell)
adaptive immune cells that orchestrate maladaptive process-driven neuropathic
pain seem to be involved in a gender-dependent manner. In this review, we
highlight the role of the microglia and peripheral immune cells in chronic
degenerative disease associated with neuro-immune-inflammatory processes.
PMID- 29342106
TI - Adrenergic Agonists Bind to Adrenergic-Receptor-Like Regions of the Mu Opioid
Receptor, Enhancing Morphine and Methionine-Enkephalin Binding: A New Approach to
"Biased Opioids"?
AB - Extensive evidence demonstrates functional interactions between the adrenergic
and opioid systems in a diversity of tissues and organs. While some effects are
due to receptor and second messenger cross-talk, recent research has revealed an
extracellular, allosteric opioid binding site on adrenergic receptors that
enhances adrenergic activity and its duration. The present research addresses
whether opioid receptors may have an equivalent extracellular, allosteric
adrenergic binding site that has similar enhancing effects on opioid binding.
Comparison of adrenergic and opioid receptor sequences revealed that these
receptors share very significant regions of similarity, particularly in some of
the extracellular and transmembrane regions associated with adrenergic binding in
the adrenergic receptors. Five of these shared regions from the mu opioid
receptor (muOPR) were synthesized as peptides and tested for binding to
adrenergic, opioid and control compounds using ultraviolet spectroscopy.
Adrenergic compounds bound to several of these muOPR peptides with low micromolar
affinity while acetylcholine, histamine and various adrenergic antagonists did
not. Similar studies were then conducted with purified, intact muOPR with similar
results. Combinations of epinephrine with methionine enkephalin or morphine
increased the binding of both by about half a log unit. These results suggest
that muOPR may be allosterically enhanced by adrenergic agonists.
PMID- 29342107
TI - Honokiol Improves Liver Steatosis in Ovariectomized Mice.
AB - Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease, and is
associated with the development of metabolic syndrome. Postmenopausal women with
estrogen deficiency are at a higher risk of progression to NAFLD. Estrogen has a
protective effect against the progression of the disease. Currently, there are no
safe and effective treatments for these liver diseases in postmenopausal women.
Honokiol (Ho), a bioactive natural product derived from Magnolia spp, has anti
inflammatory, anti-angiogenic, and anti-oxidative properties. In our study, we
investigated the beneficial effects of Ho on NAFLD in ovariectomized (OVX) mice.
We divided the mice into four groups, as follows: SHAM, OVX, OVX+beta-estradiol
(0.4 mg/kg of bodyweight), and OVX+Ho (50 mg/kg of diet). Mice were fed diets
with/without Ho for 12 weeks. The bodyweight, epidermal fat, and weights of liver
tissue were lower in the OVX group than in the other groups. Ho improved hepatic
steatosis and reduced proinflammatory cytokine levels. Moreover, Ho markedly
downregulated plasma lipid levels. Our results indicate that Ho ameliorated OVX
induced fatty liver and inflammation, as well as associated lipid metabolism.
These findings suggest that Ho may be hepatoprotective against NAFLD in
postmenopausal women.
PMID- 29342108
TI - Different Lipid Regulation in Ovarian Cancer: Inhibition of the Immune System.
AB - Lipid metabolism is altered in several cancer settings leading to different
ratios of intermediates. Ovarian cancer is the most lethal gynecological
malignancy. Cancer cells disperse in the abdominal space and ascites occurs. T
cells obtained from ascites are unable to proliferate after an antigenic
stimulus. The proliferation of ascites-derived T cells can be restored after
culturing the cells for ten days in normal culture medium. No pathway aberrancies
were detected. The acellular fraction of ascites can inhibit the proliferation of
autologous as well as allogeneic peripheral blood lymphocytes, indicating the
presence of soluble factors that interfere with T cell functionality. Therefore,
we analyzed 109 lipid mediators and found differentially regulated lipids in
suppressive ascitic fluid compared to normal abdominal fluid. Our study indicates
the presence of lipid intermediates in ascites of ovarian cancer patients, which
coincidences with T cell dysfunctionality. Since the immune system in the
abdominal cavity is compromised, this may explain the high seeding efficiency of
disseminated tumor cells. Further research is needed to fully understand the
correlation between the various lipids and T cell proliferation, which could lead
to new treatment options.
PMID- 29342109
TI - Sources of Added Sugars in Young Children, Adolescents, and Adults with Low and
High Intakes of Added Sugars.
AB - High intake of added sugars is associated with excess energy intake and poorer
diet quality. The objective of this cross-sectional study (n = 16,806) was to
estimate usual intakes and the primary food sources of added sugars across the
range of intakes (i.e., deciles) among U.S. children (2-8 years), adolescents and
teens (9-18 years), and adults (>=19 years) using the National Health and
Nutrition Examination (NHANES) data from 2009-2012. The percent energy
contributed by added sugars was 14.3 +/- 0.2% (2-8 years), 16.2 +/- 0.2% (9-18
years), and 13.1 +/- 0.2% (>=19 years), suggesting the highest intakes are among
adolescents and teens. However, the primary foods/beverages that contribute to
added sugars were remarkably consistent across the range of intakes, with the
exception of the lowest decile, and include sweetened beverages and sweet bakery
products. Interestingly across all age groups, even those in the lowest decile of
added sugars exceed the 10% guidelines. Additional foods contributing to high
intakes were candy and other desserts (e.g., ice cream) in children and
adolescents, and coffee and teas in adults. Tailoring public health messaging to
reduce intakes of these identified food groups may be of utility in designing
effective strategies to reduce added sugar intake in the U.S.
PMID- 29342110
TI - Medlay: A Reconfigurable Micro-Power Management to Investigate Self-Powered
Systems.
AB - In self-powered microsystems, a power management is essential to extract,
transfer and regulate power from energy harvesting sources to loads such as
sensors. The challenge is to consider all of the different structures and
components available and build the optimal power management on a microscale. The
purpose of this paper is to streamline the design process by creating a novel
reconfigurable testbed called Medlay. First, we propose a uniform interface for
management functions e.g., power conversion, energy storing and power routing.
This interface results in a clear layout because power and status pins are
strictly separated, and inputs and outputs have fixed positions. Medlay is the
ready-to-use and open-hardware platform based on the interface. It consists of a
base board and small modules incorporating e.g., dc-dc converters, power switches
and supercapacitors. Measurements confirm that Medlay represents a system on one
circuit board, as parasitic effects of the interconnections are negligible. The
versatility regarding different setups on the testbed is determined to over
250,000 combinations by layout graph grammar. Lastly, we underline the
applicability by recreating three state-of-the-art systems with the testbed. In
conclusion, Medlay facilitates building and testing power management in a very
compact, clear and extensible fashion.
PMID- 29342111
TI - Cytotoxicity Evaluation of Turmeric Extract Incorporated Oil-in-Water
Nanoemulsion.
AB - To overcome the drawbacks of conventional drug delivery system, nanoemulsion have
been developed as an advanced form for improving the delivery of active
ingredients. However, safety evaluation is crucial during the development stage
before the commercialization. Therefore, the aim of this study was to evaluate
the cytotoxicity of two types of newly developed nanoemulsions. Turmeric extract
loaded nanoemulsion powder-10.6 (TE-NEP-10.6, high content of artificial
surfactant Tween 80), which forms the optimal nanoemulsion, and the TE-NEP-8.6
made by increasing the content of natural emulsifier (lecithin) to reduce the
potential toxicity of nanoemulsion were cultured with various cells (NIH3T3,
H9C2, HepG2, hCPC, and hEPC) and the changes of each cell were observed followed
by nanoemulsion treatment. As a result, the two nanoemulsions (TE-NEP-10.6 and TE
NEP-8.6) did not show significant difference in cell viability. In the case of
cell line (NIH3T3, H9C2, and HepG2), toxicity was not observed at an experimental
concentration of less than 1 mg/mL, however, the cell survival rate decreased in
a concentration dependent manner in the case of primary cultured cells. These
results from our study can be used as a basic data to confirm the cell type
dependent toxicity of nanoemulsion.
PMID- 29342112
TI - Useful Bicistronic Reporter System for Studying Poly(A) Site-Defining cis
Elements and Regulation of Alternative Polyadenylation.
AB - The link between polyadenylation (pA) and various biological, behavioral, and
pathological events of eukaryotes underlines the need to develop in vivo
polyadenylation assay methods for characterization of the cis-acting elements,
trans-acting factors and environmental stimuli that affect polyadenylation
efficiency and/or relative usage of two alternative polyadenylation (APA) sites.
The current protein-based CAT or luciferase reporter systems can measure the
polyadenylation efficiency of a single pA site or candidate cis element but not
the choice of two APA sites. To address this issue, we developed a set of four
new bicistronic reporter vectors that harbor either two luciferase or
fluorescence protein open reading frames connected with one Internal Ribosome
Entry Site (IRES). Transfection of single or dual insertion constructs of these
vectors into mammalian cells demonstrated that they could be utilized not only to
quantify the strength of a single candidate pA site or cis element, but also to
accurately measure the relative usage of two APA sites at both the mRNA (qRT-PCR)
and protein levels. This represents the first reporter system that can study
polyadenylation efficiency of a single pA site or element and regulation of two
APA sites at both the mRNA and protein levels.
PMID- 29342114
TI - GaN-Based Laser Wireless Power Transfer System.
AB - The aim of this work is to present a potential application of gallium nitride
based optoelectronic devices. By using a laser diode and a photodetector, we
designed and demonstrated a free-space compact and lightweight wireless power
transfer system, whose efficiency is limited by the efficiency of the receiver.
We analyzed the effect of the electrical load, temperature, partial absorption
and optical excitation distribution on the efficiency, by identifying heating and
band-filling as the most impactful processes. By comparing the final demonstrator
with a commercial RF-based Qi system, we conclude that the efficiency is still
low at close range, but is promising in medium to long range applications.
Efficiency may not be a limiting factor, since this concept can enable entirely
new possibilities and designs, especially relevant for space applications.
PMID- 29342113
TI - Mitochondria, Oxidative Stress and the Kynurenine System, with a Focus on Ageing
and Neuroprotection.
AB - In this review, the potential causes of ageing are discussed. We seek to gain
insight into the main physiological functions of mitochondria and discuss
alterations in their function and the genome, which are supposed to be the
central mechanisms in senescence. We conclude by presenting the potential
modulating role of the kynurenine pathway in the ageing processes. Mitochondrial
dynamics are supposed to have important physiological roles in maintaining cell
homeostasis. During ageing, a decrease in mitochondrial dynamics was reported,
potentially compromising the function of mitochondria. Mitochondrial biogenesis
not only encompasses mitochondrial dynamics, but also the regulation of
transcription and translation of genes, and mitochondria are supposed to play a
prominent role in cell death during senescence. Defects in the mtDNA replication
machinery and failure in the repair of mtDNA might result in the accumulation of
mutations, leading to mitochondrial dysfunction and bioenergetic failure of the
cell. The role of reactive oxygen species (ROS) in the ageing processes is widely
acknowledged. Exaggerated oxidative damage to mDNA is supposed to take place
during senescence, including single-nucleotide base alterations, nucleotide base
pair alterations, chain breaks and cross linkage. A broad repertoire for the
repair of DNA faults has evolved, but they do not function efficiently during
senescence. Poly (ADP-ribose) polymerase (PARP) is an enzyme that assists in DNA
repair, i.e., it participates in the repair of single-stranded DNA nicks,
initiating base excision repair (BER). In the case of extensive DNA damage, PARP
1 becomes overactivated and rapidly depletes the intracellular NAD+ and ATP
pools. This results in a profound energy loss of the cell and leads to cell
dysfunction, or even cell death. Alterations in the kynurenine system have been
linked with ageing processes and several age-related disorders. The kynurenine
pathway degrades tryptophan (TRP) to several metabolites, among others kynurenine
(KYN), kynurenic acid (KYNA) and quinolinic acid (QUIN). The end product of the
route is NAD+. The first metabolic reaction is mediated by TRP-2,3-dioxygenase
(TDO) or indolamine-2,3-dioxygenases (IDO), the latter being induced by
inflammation, and it is thought to have a significant role in several disorders
and in ageing. Research is currently focusing on the KYN pathway, since several
intermediates possess neuro- and immunoactive properties, and hence are capable
of modulating the activity of certain brain cells and inflammatory responses.
During ageing, and in many age-associated disorders like obesity, dyslipidaemia,
hypertension, insulin resistance and neurodegenerative diseases, low-grade,
sustained inflammation and upregulation of IDO have been reported. However, TRP
downstream catabolites create a negative feedback loop by weakening the activated
immune system through several actions, including a decline in the Th1 response
and an enhancement of Th2-type processes. The broad actions of the KYN
intermediates in brain excitation/inhibition and their role in regulating immune
responses may provide the possibility of modifying the pathological processes in
an array of age-associated diseases in the future.
PMID- 29342115
TI - Investigating the Associations between Ethnic Networks, Community Social Capital,
and Physical Health among Marriage Migrants in Korea.
AB - This study examines factors associated with the physical health of Korea's
growing immigrant population. Specifically, it focuses on the associations
between ethnic networks, community social capital, and self-rated health (SRH)
among female marriage migrants. For empirical testing, secondary analysis of a
large nationally representative sample (NSMF 2009) is conducted. Given the
clustered data structure (individuals nested in communities), a series of two
level random intercepts and slopes models are fitted to probe the relationships
between SRH and interpersonal (bonding and bridging) networks among foreign-born
wives in Korea. In addition to direct effects, cross-level interaction effects
are investigated using hierarchical linear modeling. While adjusting for
confounders, bridging (inter-ethnic) networks are significantly linked with
better health. Bonding (co-ethnic) networks, to the contrary, are negatively
associated with immigrant health. Net of individual-level covariates, living in a
commuijnity with more aggregate bridging social capital is positively linked with
health. Community-level bonding social capital, however, is not a significant
predictor. Lastly, two cross-level interaction terms are found. First, the
positive relationship between bridging network and health is stronger in
residential contexts with more aggregate bridging social capital. Second, it is
weaker in communities with more aggregate bonding social capital.
PMID- 29342117
TI - Assessment of TSPO in a Rat Experimental Autoimmune Myocarditis Model: A
Comparison Study between [18F]Fluoromethyl-PBR28 and [18F]CB251.
AB - Overexpression of the 18-kDa translocator protein (TSPO) is closely linked to
inflammatory responses in the heart, including myocarditis, which can lead to
myocardial necrosis. In vivo assessment of inflammatory responses has enabled the
precise diagnosis of myocarditis to improve clinical outcomes. Here, we evaluated
TSPO overexpression in a rat model of experimental autoimmune myocarditis (EAM)
compared to healthy rats using two TSPO radiotracers, [18F]fluoromethyl-PBR28
([18F]1) and [18F]CB251 ([18F]2). All radiolabeling methods were successfully
applied to an automated module for the reproducible preparation of TSPO
radiotracers. Both radiotracers were directly compared in an EAM rat model, as
well as in healthy rats to determine whether either radiotracer provides a more
promising assessment of in vivo TSPO overexpression. [18F]2 provided more
specific TSPO-uptake in the heart of the EAM rats (1.32-fold that of the heart-to
lung uptake ratio versus healthy controls), while [18F]1 did not show a
significant difference between the two groups. Histopathological characterization
revealed that a prominent positron emission tomography (PET) signal of [18F]2 in
the EAM rats corresponded to the presence of a higher density of TSPO compared to
the healthy controls. These results suggest that the imidazole[1,2-a]pyridine
based radiotracer [18F]2 is a sensitive tool for noninvasively diagnosing
myocarditis related to inflammation of the heart muscle by assessing abnormal
TSPO expression.
PMID- 29342118
TI - Microbial Degradation Behavior in Seawater of Polyester Blends Containing Poly(3
hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx).
AB - The microbial degradation behavior of poly(3-hydroxybutyrate-co-3
hydroxyhexanoate) (PHBHHx) and its compound with several polyesters such as
poly(butylene adipate-co-telephtharate) (PBAT), poly(butylene succinate) (PBS),
and polylactic acid (PLA) in seawater was tested by a biological oxygen demand
(BOD) method. PHBHHx showed excellent biodegradation in seawater in this study.
In addition, the biodegradation rate of several blends was much influenced by the
weight ratio of PHBHHx in their blends and decreased in accordance with the
decrement of PHBHHX ratio. The surface morphology of the sheet was important
factor for controlling the biodegradation rate of PHBHHx-containing blends in
seawater.
PMID- 29342119
TI - Novel Hybrid Formulations Based on Thiourea Derivatives and Core@Shell Fe3O4@C18
Nanostructures for the Development of Antifungal Strategies.
AB - The continuously increasing global impact of fungal infections is requiring the
rapid development of novel antifungal agents. Due to their multiple
pharmacological activities, thiourea derivatives represent privileged candidates
for shaping new drugs. We report here the preparation, physico-chemical
characterization and bioevaluation of hybrid nanosystems based on new 2-((4
chlorophenoxy)methyl)-N-(substituted phenylcarbamo-thioyl)benzamides and
Fe3O4@C18 core@shell nanoparticles. The new benzamides were prepared by an
efficient method, then their structure was confirmed by spectral studies and
elemental analysis and they were further loaded on Fe3O4@C18 nanostructures. Both
the obtained benzamides and the resulting hybrid nanosystems were tested for
their efficiency against planktonic and adherent fungal cells, as well as for
their in vitro biocompatibility, using mesenchymal cells. The antibiofilm
activity of the obtained benzamides was dependent on the position and nature of
substituents, demonstrating that structure modulation could be a very useful
approach to enhance their antimicrobial properties. The hybrid nanosystems have
shown an increased efficiency in preventing the development of Candida albicans
(C. albicans) biofilms and moreover, they exhibited a good biocompatibility,
suggesting that Fe3O4@C18core@shell nanoparticles could represent promising
nanocarriers for antifungal substances, paving the way to the development of
novel effective strategies with prophylactic and therapeutic value for fighting
biofilm associated C. albicans infections.
PMID- 29342116
TI - VEGF Signaling in Neurological Disorders.
AB - Vascular endothelial growth factor (VEGF) is a potent growth factor playing
diverse roles in vasculogenesis and angiogenesis. In the brain, VEGF mediates
angiogenesis, neural migration and neuroprotection. As a permeability factor,
excessive VEGF disrupts intracellular barriers, increases leakage of the choroid
plexus endothelia, evokes edema, and activates the inflammatory pathway.
Recently, we discovered that a heparin binding epidermal growth factor like
growth factor (HB-EGF)-a class of EGF receptor (EGFR) family ligands-contributes
to the development of hydrocephalus with subarachnoid hemorrhage through
activation of VEGF signaling. The objective of this review is to entail a recent
update on causes of death due to neurological disorders involving cerebrovascular
and age-related neurological conditions and to understand the mechanism by which
angiogenesis-dependent pathological events can be treated with VEGF antagonisms.
The Global Burden of Disease study indicates that cancer and cardiovascular
disease including ischemic and hemorrhagic stroke are two leading causes of death
worldwide. The literature suggests that VEGF signaling in ischemic brains
highlights the importance of concentration, timing, and alternate route of
modulating VEGF signaling pathway. Molecular targets distinguishing two distinct
pathways of VEGF signaling may provide novel therapies for the treatment of
neurological disorders and for maintaining lower mortality due to these
conditions.
PMID- 29342121
TI - beta-Escin Effectively Modulates HUVECS Proliferation and Tube Formation.
AB - In the present study we evaluated the anti-angiogenic activities of beta-escin
(the major active compound of Aesculus hippocastanum L. seeds). Human umbilical
vein endothelial cells (HUVECs) were used as an in vitro model for studying the
molecular mechanism underlying the anti-angiogenic effect of beta-escin. We
investigated the in vitro effects on proliferation, migration, and tube formation
of HUVECs and in vivo anti-angiogenic activity was evaluated in a chick
chorioallantoic membrane (CAM) angiogenesis assay. Moreover, the effect on gene
expressions was determined by the RT2 ProfilerTM human angiogenesis PCR Array. It
was found that beta-escin exerts inhibitory effect on the basic fibroblast growth
factor (bFGF)-induced proliferation, migration and tube formation, as well as CAM
angiogenesis in vivo. The inhibition of critical steps of angiogenic process
observed with beta-escin could be partially explained by suppression of Akt
activation in response to bFGF. Moreover, the anti-angiogenic effects of beta
escin could also be mediated via inhibition of EFNB2 and FGF-1 gene expressions
in endothelial cells. In conclusion, beta-escin affects endothelial cells as a
negative mediator of angiogenesis in vitro and in vivo and may therefore be
considered as a promising candidate for further research elucidating its
underlying mechanism of action.
PMID- 29342122
TI - Synthesis and Characterization of a Heterometallic Extended Architecture Based on
a Manganese(II)-Substituted Sandwich-Type Polyoxotungstate.
AB - The reaction of [alpha-P2W15O56]12- with MnII and DyIII in an aqueous basic
solution led to the isolation of an all inorganic heterometallic aggregate
Na10(OH2)42[{Dy(H2O)6}2Mn4P4W30O112(H2O)2].17H2O (Dy2Mn4-P2W15). Single-crystal X
ray diffraction revealed that Dy2Mn4-P2W15 crystallizes in the triclinic system
with space group P 1 - , and consists of a tetranuclear manganese(II)-substituted
sandwich-type phosphotungstate [Mn4(H2O)2(P2W15O56)2]16- (Mn4-P2W15), Na, and
DyIII cations. Compound Dy2Mn4-P2W15 exhibits a 1D ladder-like chain structure
based on sandwich-type segments and dysprosium cations as linkers, which are
further connected into a three-dimensional open framework by sodium cations. The
title compound was structurally and compositionally characterized in solid state
by single-crystal XRD, powder X-ray diffraction (PXRD), Fourier-transform
infrared spectroscopy (FTIR), thermogravimetric (TGA), and elemental analyses.
Further, the absorption and emission electronic spectra in aqueous solutions of
Dy2Mn4-P2W15 and Mn4-P2W15 were studied. Also, magnetic properties were studied
and compared with the magnetic behavior of [Mn4(H2O)2(P2W15O56)2]16-.
PMID- 29342123
TI - Image-Based Localization Aided Indoor Pedestrian Trajectory Estimation Using
Smartphones.
AB - Accurately determining pedestrian location in indoor environments using consumer
smartphones is a significant step in the development of ubiquitous localization
services. Many different map-matching methods have been combined with pedestrian
dead reckoning (PDR) to achieve low-cost and bias-free pedestrian tracking.
However, this works only in areas with dense map constraints and the error
accumulates in open areas. In order to achieve reliable localization without map
constraints, an improved image-based localization aided pedestrian trajectory
estimation method is proposed in this paper. The image-based localization
recovers the pose of the camera from the 2D-3D correspondences between the 2D
image positions and the 3D points of the scene model, previously reconstructed by
a structure-from-motion (SfM) pipeline. This enables us to determine the initial
location and eliminate the accumulative error of PDR when an image is
successfully registered. However, the image is not always registered since the
traditional 2D-to-3D matching rejects more and more correct matches when the
scene becomes large. We thus adopt a robust image registration strategy that
recovers initially unregistered images by integrating 3D-to-2D search. In the
process, the visibility and co-visibility information is adopted to improve the
efficiency when searching for the correspondences from both sides. The
performance of the proposed method was evaluated through several experiments and
the results demonstrate that it can offer highly acceptable pedestrian
localization results in long-term tracking, with an error of only 0.56 m, without
the need for dedicated infrastructures.
PMID- 29342124
TI - The Root of Atractylodes macrocephala Koidzumi Prevents Obesity and Glucose
Intolerance and Increases Energy Metabolism in Mice.
AB - Targeting energy expenditure offers a strategy for treating obesity more
effectively and safely. In previous studies, we found that the root of
Atractylodes macrocephala Koidzumi (Atractylodis Rhizoma Alba, ARA) increased
energy metabolism in C2C12 cells. Here, we investigated the effects of ARA on
obesity and glucose intolerance by examining energy metabolism in skeletal muscle
and brown fat in high-fat diet (HFD) induced obese mice. ARA decreased body
weight gain, hepatic lipid levels and serum total cholesterol levels, but did not
modify food intake. Fasting serum glucose, serum insulin levels and glucose
intolerance were all improved in ARA treated mice. Furthermore, ARA increased
peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1alpha)
expression, and the phosphorylation of adenosine monophosphate-activated protein
kinase (AMPK) in skeletal muscle tissues, and also prevented skeletal muscle
atrophy. In addition, the numbers of brown adipocytes and the expressions of
PGC1alpha and uncoupling protein 1 (UCP1) were elevated in the brown adipose
tissues of ARA treated mice. Our results show that ARA can prevent diet-induced
obesity and glucose intolerance in C5BL/6 mice and suggests that the mechanism
responsible is related to the promotion of energy metabolism in skeletal muscle
and brown adipose tissues.
PMID- 29342126
TI - Tailoring Cu Nanoparticle Catalyst for Methanol Synthesis Using the Spinning Disk
Reactor.
AB - Cu nanoparticles are known to be very active for methanol (MeOH) synthesis at
relatively low temperatures, such that smaller particle sizes yield better MeOH
productivity. We aimed to control Cu nanoparticle (NP) size and size distribution
for catalysing MeOH synthesis, by using the spinning disk reactor. The spinning
disk reactor (SDR), which operates based on shear effect and plug flow in thin
films, can be used to rapidly micro-mix reactants in order to control nucleation
and particle growth for uniform particle size distribution. This could be
achieved by varying both physical and chemical operation conditions in a
precipitation reaction on the SDR. We have used the SDR for a Cu borohydride
reduction to vary Cu NP size from 3 nm to about 55 nm. XRD and TEM
characterization confirmed the presence of Cu2O and Cu crystallites when the
samples were dried. This technique is readily scalable for Cu NP production by
processing continuously over a longer duration than the small-scale tests.
However, separation of the nanoparticles from solution posed a challenge as the
suspension hardly settled. The Cu NPs produced were tested to be active catalyst
for MeOH synthesis at low temperature and MeOH productivity increased with
decreasing particle size.
PMID- 29342125
TI - Induction of Pro-Apoptotic Endoplasmic Reticulum Stress in Multiple Myeloma Cells
by NEO214, Perillyl Alcohol Conjugated to Rolipram.
AB - Despite the introduction of new therapies for multiple myeloma (MM), many
patients are still dying from this disease and novel treatments are urgently
needed. We have designed a novel hybrid molecule, called NEO214, that was
generated by covalent conjugation of the natural monoterpene perillyl alcohol
(POH), an inducer of endoplasmic reticulum (ER) stress, to rolipram (Rp), an
inhibitor of phosphodiesterase-4 (PDE4). Its potential anticancer effects were
investigated in a panel of MM cell lines. We found that NEO214 effectively killed
MM cells in vitro with a potency that was over an order of magnitude stronger
than that of its individual components, either alone or in combination. The
cytotoxic mechanism of NEO214 involved severe ER stress and prolonged induction
of CCAAT/enhancer-binding protein homologous protein (CHOP), a key pro-apoptotic
component of the ER stress response. These effects were prevented by salubrinal,
a pharmacologic inhibitor of ER stress, and by CHOP gene knockout. Conversely,
combination of NEO214 with bortezomib, a drug in clinical use for patients with
MM, resulted in synergistic enhancement of MM cell death. Combination with the
adenylate cyclase stimulant forskolin did not enhance NEO214 impact, indicating
that cyclic adenosine 3',5'-monophosphate (AMP) pathways might play a lesser
role. Our study introduces the novel agent NEO214 as a potent inducer of ER
stress with significant anti-MM activity in vitro. It should be further
investigated as a potential MM therapy aimed at exploiting this tumor's distinct
sensitivity to ER stress.
PMID- 29342127
TI - Enhancement in Corneal Permeability of Dissolved Carteolol by Its Combination
with Magnesium Hydroxide Nanoparticles.
AB - We prepared magnesium hydroxide (MH) nanoparticles, and investigated their effect
when combined with dissolved carteolol on the bioavailability and intraocular
pressure (IOP)-reducing effect of carteolol. The carteolol was solved in saline
containing additives (0.5% methylcellulose, 0.001% benzalkonium chloride, 0.5%
mannitol; CRT-solution). MH nanoparticles were prepared by a bead mill method
with additives. Then carteolol/MH microparticle and carteolol/MH nanoparticle
fixed combinations (mCMFC and nCMFC) were prepared by mixing the CRT-solution and
MH particles. The transcorneal penetration and IOP-reducing effect of carteolol
was evaluated in rabbits. The mean particle size of mCMFC was 7.2 MUm, and the
particle size was reduced to 73.5-113.5 nm by the bead mill treatment. The MH
particles in nCMFC remained in the nano size range for 8 days after preparation,
and the amounts of lacrimal fluid and corneal damage were unchanged by repetitive
instillation of nCMFC (twice a day for 4 weeks). The transcorneal penetration of
carteolol was enhanced by the combination with MH nanoparticles, and the IOP
reducing effect of nCMFC was significantly higher than that of CRT-solution or
mCMFC. In conclusion, we designed nCMFC, and showed that the high levels of
dissolved carteolol can be delivered into the aqueous humor by the instillation
of nCMFC. Combination with MH nanoparticles may achieve an enhancement of corneal
penetration for water-soluble drugs. These findings provide significant
information that can be used to design further studies aimed at developing anti
glaucoma eye drugs.
PMID- 29342128
TI - The Effect of Emulsion Intensity on Selected Sensory and Instrumental Texture
Properties of Full-Fat Mayonnaise.
AB - Varying processing conditions can strongly affect the microstructure of
mayonnaise, opening up new applications for the creation of products tailored to
meet different consumer preferences. The aim of the study was to evaluate the
effect of emulsification intensity on sensory and instrumental characteristics of
full-fat mayonnaise. Mayonnaise, based on a standard recipe, was processed at low
and high emulsification intensities, with selected sensory and instrumental
properties then evaluated using an analytical panel and a back extrusion method.
The evaluation also included a commercial reference mayonnaise. The overall
effects of a higher emulsification intensity on the sensory and instrumental
characteristics of full-fat mayonnaise were limited. However, texture was
affected, with a more intense emulsification resulting in a firmer mayonnaise
according to both back extrusion data and the analytical sensory panel.
Appearance, taste and flavor attributes were not affected by processing.
PMID- 29342129
TI - Fabrication, Structural Characterization and Uniaxial Tensile Properties of Novel
Sintered Multi-Layer Wire Mesh Porous Plates.
AB - There is an increasing interest in developing porous metals or metallic foams for
functional and structural applications. The study of the physical and mechanical
properties of porous metals is very important and helpful for their application.
In this paper, a novel sintered multilayer wire mesh porous plate material
(WMPPs) with a thickness of 0.5 mm-3 mm and a porosity of 10-35% was prepared by
winding, pressing, rolling, and subsequently vacuum sintering them. The pore size
and total size distribution in the as-prepared samples were investigated using
the bubble point method. The uniaxial tensile behavior of the WMPPs was
investigated in terms of the sintering temperature, porosity, wire diameter, and
manufacturing technology. The deformation process and the failure mechanism under
the tensile press was also discussed based on the appearance of the fractures
(SEM figures). The results indicated that the pore size and total size
distribution were closely related to the raw material used and the sintering
temperature. For the WMPPs prepared by the wire mesh, the pore structures were
inerratic and the vast majority of pore size was less than 10 MUm. On the other
hand, for the WMPPs that were prepared by wire mesh and powder, the pore
structures were irregular and the pore size ranged from 0 MUm-50 MUm. The
experimental data showed that the tensile strength of WMPPs is much higher than
any other porous metals or metallic foams. Higher sintering temperatures led to
coarser joints between wires and resulted in higher tensile strength. The
sintering temperature decreased from 1330 degrees C to 1130 degrees C and the
tensile strength decreased from 296 MPa to 164 MPa. Lower porosity means that
there are more metallurgical joints and metallic frameworks resisting deformation
per unit volume. Therefore, lower porosities exhibit higher tensile strength. An
increase of porosity from 17.14% to 32.5% led to the decrease of the tensile
strength by 90 MPa. The coarser wires led to a bigger contact area between the
interconnecting wires, resulting in a stronger sintering neck that exhibited
higher tensile strength. The wire diameter increased from 81 MUm to 122 MUm and
the tensile strength increased from 296 MPa to 362 MPa. The fracture morphology
showed that the wires experience necking deformation and ductile fracture.
PMID- 29342130
TI - Thyroid-Stimulating Hormone Levels Are Positively Associated with Insulin
Resistance.
AB - BACKGROUND It has been reported that overt and mild thyroid dysfunctions are
associated with insulin resistance (IR). We performed this retrospective study to
evaluate the relationships between thyroid-stimulating hormone (TSH) levels
within the reference range and IR. MATERIAL AND METHODS A total of 447
outpatients were enrolled in this study: 298 with type 2 diabetes mellitus and
149 nondiabetic individuals. Based on a cutoff HbA1c value of 7%, diabetic
patients were additionally divided into 2 groups: a high-HbA1c group (n=240) and
a low-HbA1c group (n=58). The relationships of TSH levels and HOMA-IR were
computed using linear regression models. RESULTS TSH levels were positively and
linearly associated with HOMA-IR in both the nondiabetic and diabetic groups
(r=0.210, p=0.011 and r=0.451, p<0.001), as well as in the high- and low-HbA1c
groups (r=0.507, p<0.001 and r=0.259, p=0.048). A better correlation between TSH
levels and HOMA-IR was found in the diabetic group and in the high-HbA1c group
when compared with the nondiabetic group and the low-HbA1c group, respectively.
Linear regression analysis showed that TSH levels were independently associated
with HOMA-IR (p=0.034, =0.049 and <0.001 in nondiabetic, low-, and high-HbA1c
groups, respectively). CONCLUSIONS Our data suggest that TSH is independently
associated with insulin resistance.
PMID- 29342131
TI - Survey of plasma proteins in children with progeria pre-therapy and on-therapy
with lonafarnib.
AB - BackgroundHutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare, fatal,
segmental premature aging syndrome caused by the aberrant lamin A protein,
progerin. The protein farnesyltransferase inhibitor, lonafarnib, ameliorates some
aspects of cardiovascular and bone disease.MethodsWe performed a prospective
longitudinal survey of plasma proteins in 24 children with HGPS (an estimated 10%
of the world's population at the time) at baseline and on lonafarnib therapy,
compared with age- and gender-matched controls using a multi-analyte, microsphere
based immunofluorescent assay.ResultsThe mean levels for 23/66 (34.8%) proteins
were significantly lower and 7/66 (10.6%) were significantly higher in HGPS
samples compared with those in controls (P<=0.05). Six proteins whose
concentrations were initially lower normalized with lonafarnib therapy:
interleukins 1alpha, 7, and 13, beta-2 microglobulin, C-reactive protein, and
myoglobin. Alpha-2 macroglobulin, a protease inhibitor associated with stroke,
was elevated at baseline and subsequently normalized with lonafarnib
therapy.ConclusionThis is the first study to employ a multi-analyte array
platform in HGPS. Novel potential biomarkers identified in this study should be
further validated by correlations with clinical disease status, especially
proteins associated with cardiovascular disease and those that normalized with
lonafarnib therapy.
PMID- 29342132
TI - Centimetre-scale electron diffusion in photoactive organic heterostructures.
AB - The unique properties of organic semiconductors, such as flexibility and
lightness, are increasingly important for information displays, lighting and
energy generation. But organics suffer from both static and dynamic disorder, and
this can lead to variable-range carrier hopping, which results in notoriously
poor electrical properties, with low electron and hole mobilities and
correspondingly short charge-diffusion lengths of less than a micrometre. Here we
demonstrate a photoactive (light-responsive) organic heterostructure comprising a
thin fullerene channel sandwiched between an electron-blocking layer and a
blended donor:C70 fullerene heterojunction that generates charges by dissociating
excitons. Centimetre-scale diffusion of electrons is observed in the fullerene
channel, and this can be fitted with a simple electron diffusion model. Our
experiments enable the direct measurement of charge diffusivity in organic
semiconductors, which is as high as 0.83 +/- 0.07 square centimetres per second
in a C60 channel at room temperature. The high diffusivity of the fullerene
combined with the extraordinarily long charge-recombination time yields diffusion
lengths of more than 3.5 centimetres, orders of magnitude larger than expected
for an organic system.
PMID- 29342133
TI - A Myc enhancer cluster regulates normal and leukaemic haematopoietic stem cell
hierarchies.
AB - The transcription factor Myc is essential for the regulation of haematopoietic
stem cells and progenitors and has a critical function in haematopoietic
malignancies. Here we show that an evolutionarily conserved region located 1.7
megabases downstream of the Myc gene that has previously been labelled as a
'super-enhancer' is essential for the regulation of Myc expression levels in both
normal haematopoietic and leukaemic stem cell hierarchies in mice and humans.
Deletion of this region in mice leads to a complete loss of Myc expression in
haematopoietic stem cells and progenitors. This caused an accumulation of
differentiation-arrested multipotent progenitors and loss of myeloid and B cells,
mimicking the phenotype caused by Mx1-Cre-mediated conditional deletion of the
Myc gene in haematopoietic stem cells. This super-enhancer comprises multiple
enhancer modules with selective activity that recruits a compendium of
transcription factors, including GFI1b, RUNX1 and MYB. Analysis of mice carrying
deletions of individual enhancer modules suggests that specific Myc expression
levels throughout most of the haematopoietic hierarchy are controlled by the
combinatorial and additive activity of individual enhancer modules, which
collectively function as a 'blood enhancer cluster' (BENC). We show that BENC is
also essential for the maintenance of MLL-AF9-driven leukaemia in mice.
Furthermore, a BENC module, which controls Myc expression in mouse haematopoietic
stem cells and progenitors, shows increased chromatin accessibility in human
acute myeloid leukaemia stem cells compared to blasts. This difference correlates
with MYC expression and patient outcome. We propose that clusters of enhancers,
such as BENC, form highly combinatorial systems that allow precise control of
gene expression across normal cellular hierarchies and which also can be hijacked
in malignancies.
PMID- 29342134
TI - Chromosomal instability drives metastasis through a cytosolic DNA response.
AB - Chromosomal instability is a hallmark of cancer that results from ongoing errors
in chromosome segregation during mitosis. Although chromosomal instability is a
major driver of tumour evolution, its role in metastasis has not been
established. Here we show that chromosomal instability promotes metastasis by
sustaining a tumour cell-autonomous response to cytosolic DNA. Errors in
chromosome segregation create a preponderance of micronuclei whose rupture spills
genomic DNA into the cytosol. This leads to the activation of the cGAS-STING
(cyclic GMP-AMP synthase-stimulator of interferon genes) cytosolic DNA-sensing
pathway and downstream noncanonical NF-kappaB signalling. Genetic suppression of
chromosomal instability markedly delays metastasis even in highly aneuploid
tumour models, whereas continuous chromosome segregation errors promote cellular
invasion and metastasis in a STING-dependent manner. By subverting lethal
epithelial responses to cytosolic DNA, chromosomally unstable tumour cells co-opt
chronic activation of innate immune pathways to spread to distant organs.
PMID- 29342135
TI - Structures of beta-klotho reveal a 'zip code'-like mechanism for endocrine FGF
signalling.
AB - Canonical fibroblast growth factors (FGFs) activate FGF receptors (FGFRs) through
paracrine or autocrine mechanisms in a process that requires cooperation with
heparan sulfate proteoglycans, which function as co-receptors for FGFR
activation. By contrast, endocrine FGFs (FGF19, FGF21 and FGF23) are circulating
hormones that regulate critical metabolic processes in a variety of tissues.
FGF19 regulates bile acid synthesis and lipogenesis, whereas FGF21 stimulates
insulin sensitivity, energy expenditure and weight loss. Endocrine FGFs signal
through FGFRs in a manner that requires klothos, which are cell-surface proteins
that possess tandem glycosidase domains. Here we describe the crystal structures
of free and ligand-bound beta-klotho extracellular regions that reveal the
molecular mechanism that underlies the specificity of FGF21 towards beta-klotho
and demonstrate how the FGFR is activated in a klotho-dependent manner. beta
Klotho serves as a primary 'zip code'-like receptor that acts as a targeting
signal for FGF21, and FGFR functions as a catalytic subunit that mediates
intracellular signalling. Our structures also show how the sugar-cutting enzyme
glycosidase has evolved to become a specific receptor for hormones that regulate
metabolic processes, including the lowering of blood sugar levels. Finally, we
describe an agonistic variant of FGF21 with enhanced biological activity and
present structural insights into the potential development of therapeutic agents
for diseases linked to endocrine FGFs.
PMID- 29342136
TI - Clonal evolution mechanisms in NT5C2 mutant-relapsed acute lymphoblastic
leukaemia.
AB - Relapsed acute lymphoblastic leukaemia (ALL) is associated with resistance to
chemotherapy and poor prognosis. Gain-of-function mutations in the 5'
nucleotidase, cytosolic II (NT5C2) gene induce resistance to 6-mercaptopurine and
are selectively present in relapsed ALL. Yet, the mechanisms involved in NT5C2
mutation-driven clonal evolution during the initiation of leukaemia, disease
progression and relapse remain unknown. Here we use a conditional-and-inducible
leukaemia model to demonstrate that expression of NT5C2(R367Q), a highly
prevalent relapsed-ALL NT5C2 mutation, induces resistance to chemotherapy with 6
mercaptopurine at the cost of impaired leukaemia cell growth and leukaemia
initiating cell activity. The loss-of-fitness phenotype of NT5C2+/R367Q mutant
cells is associated with excess export of purines to the extracellular space and
depletion of the intracellular purine-nucleotide pool. Consequently, blocking
guanosine synthesis by inhibition of inosine-5'-monophosphate dehydrogenase
(IMPDH) induced increased cytotoxicity against NT5C2-mutant leukaemia
lymphoblasts. These results identify the fitness cost of NT5C2 mutation and
resistance to chemotherapy as key evolutionary drivers that shape clonal
evolution in relapsed ALL and support a role for IMPDH inhibition in the
treatment of ALL.
PMID- 29342137
TI - Corrigendum: mTORC1-dependent AMD1 regulation sustains polyamine metabolism in
prostate cancer.
AB - This corrects the article DOI: 10.1038/nature22964.
PMID- 29342138
TI - alpha-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling.
AB - The ageing suppressor alpha-klotho binds to the fibroblast growth factor receptor
(FGFR). This commits FGFR to respond to FGF23, a key hormone in the regulation of
mineral ion and vitamin D homeostasis. The role and mechanism of this co-receptor
are unknown. Here we present the atomic structure of a 1:1:1 ternary complex that
consists of the shed extracellular domain of alpha-klotho, the FGFR1c ligand
binding domain, and FGF23. In this complex, alpha-klotho simultaneously tethers
FGFR1c by its D3 domain and FGF23 by its C-terminal tail, thus implementing FGF23
FGFR1c proximity and conferring stability. Dimerization of the stabilized ternary
complexes and receptor activation remain dependent on the binding of heparan
sulfate, a mandatory cofactor of paracrine FGF signalling. The structure of alpha
klotho is incompatible with its purported glycosidase activity. Thus, shed alpha
klotho functions as an on-demand non-enzymatic scaffold protein that promotes
FGF23 signalling.
PMID- 29342139
TI - Structure and mutagenesis reveal essential capsid protein interactions for KSHV
replication.
AB - Kaposi's sarcoma-associated herpesvirus (KSHV) causes Kaposi's sarcoma, a cancer
that commonly affects patients with AIDS and which is endemic in sub-Saharan
Africa. The KSHV capsid is highly pressurized by its double-stranded DNA genome,
as are the capsids of the eight other human herpesviruses. Capsid assembly and
genome packaging of herpesviruses are prone to interruption and can therefore be
targeted for the structure-guided development of antiviral agents. However,
herpesvirus capsids-comprising nearly 3,000 proteins and over 1,300 A in diameter
present a formidable challenge to atomic structure determination and functional
mapping of molecular interactions. Here we report a 4.2 A resolution structure of
the KSHV capsid, determined by electron-counting cryo-electron microscopy, and
its atomic model, which contains 46 unique conformers of the major capsid protein
(MCP), the smallest capsid protein (SCP) and the triplex proteins Tri1 and Tri2.
Our structure and mutagenesis results reveal a groove in the upper domain of the
MCP that contains hydrophobic residues that interact with the SCP, which in turn
crosslinks with neighbouring MCPs in the same hexon to stabilize the capsid.
Multiple levels of MCP-MCP interaction-including six sets of stacked hairpins
lining the hexon channel, disulfide bonds across channel and buttress domains in
neighbouring MCPs, and an interaction network forged by the N-lasso domain and
secured by the dimerization domain-define a robust capsid that is resistant to
the pressure exerted by the enclosed genome. The triplexes, each composed of two
Tri2 molecules and a Tri1 molecule, anchor to the capsid floor via a Tri1 N
anchor to plug holes in the MCP network and rivet the capsid floor. These
essential roles of the MCP N-lasso and Tri1 N-anchor are verified by serial
truncation mutageneses. Our proof-of-concept demonstration of the use of
polypeptides that mimic the smallest capsid protein to inhibit KSHV lytic
replication highlights the potential for exploiting the interaction hotspots
revealed in our atomic structure to develop antiviral agents.
PMID- 29342140
TI - Atomic structure of the eukaryotic intramembrane RAS methyltransferase ICMT.
AB - The maturation of RAS GTPases and approximately 200 other cellular CAAX proteins
involves three enzymatic steps: addition of a farnesyl or geranylgeranyl prenyl
lipid to the cysteine (C) in the C-terminal CAAX motif, proteolytic cleavage of
the AAX residues and methylation of the exposed prenylcysteine residue at its
terminal carboxylate. This final step is catalysed by isoprenylcysteine carboxyl
methyltransferase (ICMT), a eukaryote-specific integral membrane enzyme that
resides in the endoplasmic reticulum. ICMT is the only cellular enzyme that is
known to methylate prenylcysteine substrates; methylation is important for the
biological functions of these substrates, such as the membrane localization and
subsequent activity of RAS, prelamin A and RAB. Inhibition of ICMT has potential
for combating progeria and cancer. Here we present an X-ray structure of ICMT, in
complex with its cofactor, an ordered lipid molecule and a monobody inhibitor, at
2.3 A resolution. The active site spans cytosolic and membrane-exposed regions,
indicating distinct entry routes for the cytosolic methyl donor, S-adenosyl-l
methionine, and for prenylcysteine substrates, which are associated with the
endoplasmic reticulum membrane. The structure suggests how ICMT overcomes the
topographical challenge and unfavourable energetics of bringing two reactants
that have different cellular localizations together in a membrane environment-a
relatively uncharacterized but defining feature of many integral membrane
enzymes.
PMID- 29342141
TI - Monitoring T cell-dendritic cell interactions in vivo by intercellular enzymatic
labelling.
AB - Interactions between different cell types are essential for multiple biological
processes, including immunity, embryonic development and neuronal signalling.
Although the dynamics of cell-cell interactions can be monitored in vivo by
intravital microscopy, this approach does not provide any information on the
receptors and ligands involved or enable the isolation of interacting cells for
downstream analysis. Here we describe a complementary approach that uses
bacterial sortase A-mediated cell labelling across synapses of immune cells to
identify receptor-ligand interactions between cells in living mice, by generating
a signal that can subsequently be detected ex vivo by flow cytometry. We call
this approach for the labelling of 'kiss-and-run' interactions between immune
cells 'Labelling Immune Partnerships by SorTagging Intercellular Contacts'
(LIPSTIC). Using LIPSTIC, we show that interactions between dendritic cells and
CD4+ T cells during T-cell priming in vivo occur in two distinct modalities: an
early, cognate stage, during which CD40-CD40L interactions occur specifically
between T cells and antigen-loaded dendritic cells; and a later, non-cognate
stage during which these interactions no longer require prior engagement of the T
cell receptor. Therefore, LIPSTIC enables the direct measurement of dynamic cell
cell interactions both in vitro and in vivo. Given its flexibility for use with
different receptor-ligand pairs and a range of detectable labels, we expect that
this approach will be of use to any field of biology requiring quantification of
intercellular communication.
PMID- 29342142
TI - Midbrain circuits that set locomotor speed and gait selection.
AB - Locomotion is a fundamental motor function common to the animal kingdom. It is
implemented episodically and adapted to behavioural needs, including exploration,
which requires slow locomotion, and escape behaviour, which necessitates faster
speeds. The control of these functions originates in brainstem structures,
although the neuronal substrate(s) that support them have not yet been
elucidated. Here we show in mice that speed and gait selection are controlled by
glutamatergic excitatory neurons (GlutNs) segregated in two distinct midbrain
nuclei: the cuneiform nucleus (CnF) and the pedunculopontine nucleus (PPN).
GlutNs in both of these regions contribute to the control of slower, alternating
gait locomotion, whereas only GlutNs in the CnF are able to elicit high-speed,
synchronous-gait locomotion. Additionally, both the activation dynamics and the
input and output connectivity matrices of GlutNs in the PPN and the CnF support
explorative and escape locomotion, respectively. Our results identify two regions
in the midbrain that act in conjunction to select context-dependent locomotor
behaviours.
PMID- 29342144
TI - Erratum: Moving beyond microbiome-wide associations to causal microbe
identification.
AB - This corrects the article DOI: 10.1038/nature25019.
PMID- 29342143
TI - Regulation of embryonic haematopoietic multipotency by EZH1.
AB - All haematopoietic cell lineages that circulate in the blood of adult mammals
derive from multipotent haematopoietic stem cells (HSCs). By contrast, in the
blood of mammalian embryos, lineage-restricted progenitors arise first,
independently of HSCs, which only emerge later in gestation. As best defined in
the mouse, 'primitive' progenitors first appear in the yolk sac at 7.5 days post
coitum. Subsequently, erythroid-myeloid progenitors that express fetal
haemoglobin, as well as fetal lymphoid progenitors, develop in the yolk sac and
the embryo proper, but these cells lack HSC potential. Ultimately, 'definitive'
HSCs with long-term, multilineage potential and the ability to engraft irradiated
adults emerge at 10.5 days post-coitum from arterial endothelium in the aorta
gonad-mesonephros and other haemogenic vasculature. The molecular mechanisms of
this reverse progression of haematopoietic ontogeny remain unexplained. We
hypothesized that the definitive haematopoietic program might be actively
repressed in early embryogenesis through epigenetic silencing, and that
alleviating this repression would elicit multipotency in otherwise lineage
restricted haematopoietic progenitors. Here we show that reduced expression of
the Polycomb group protein EZH1 enhances multi-lymphoid output from human
pluripotent stem cells. In addition, Ezh1 deficiency in mouse embryos results in
precocious emergence of functional definitive HSCs in vivo. Thus, we identify
EZH1 as a repressor of haematopoietic multipotency in the early mammalian embryo.
PMID- 29342145
TI - The gram-negative bacterial periplasm: Size matters.
AB - Gram-negative bacteria are surrounded by two membrane bilayers separated by a
space termed the periplasm. The periplasm is a multipurpose compartment separate
from the cytoplasm whose distinct reducing environment allows more efficient and
diverse mechanisms of protein oxidation, folding, and quality control. The
periplasm also contains structural elements and important environmental sensing
modules, and it allows complex nanomachines to span the cell envelope. Recent
work indicates that the size or intermembrane distance of the periplasm is
controlled by periplasmic lipoproteins that anchor the outer membrane to the
periplasmic peptidoglycan polymer. This periplasm intermembrane distance is
critical for sensing outer membrane damage and dictates length of the flagellar
periplasmic rotor, which controls motility. These exciting results resolve
longstanding debates about whether the periplasmic distance has a biological
function and raise the possibility that the mechanisms for maintenance of
periplasmic size could be exploited for antibiotic development.
PMID- 29342146
TI - A theory of how active behavior stabilises neural activity: Neural gain
modulation by closed-loop environmental feedback.
AB - During active behaviours like running, swimming, whisking or sniffing, motor
actions shape sensory input and sensory percepts guide future motor commands.
Ongoing cycles of sensory and motor processing constitute a closed-loop feedback
system which is central to motor control and, it has been argued, for perceptual
processes. This closed-loop feedback is mediated by brainwide neural circuits but
how the presence of feedback signals impacts on the dynamics and function of
neurons is not well understood. Here we present a simple theory suggesting that
closed-loop feedback between the brain/body/environment can modulate neural gain
and, consequently, change endogenous neural fluctuations and responses to sensory
input. We support this theory with modeling and data analysis in two vertebrate
systems. First, in a model of rodent whisking we show that negative feedback
mediated by whisking vibrissa can suppress coherent neural fluctuations and
neural responses to sensory input in the barrel cortex. We argue this suppression
provides an appealing account of a brain state transition (a marked change in
global brain activity) coincident with the onset of whisking in rodents.
Moreover, this mechanism suggests a novel signal detection mechanism that
selectively accentuates active, rather than passive, whisker touch signals. This
mechanism is consistent with a predictive coding strategy that is sensitive to
the consequences of motor actions rather than the difference between the
predicted and actual sensory input. We further support the theory by re-analysing
previously published two-photon data recorded in zebrafish larvae performing
closed-loop optomotor behaviour in a virtual swim simulator. We show, as
predicted by this theory, that the degree to which each cell contributes in
linking sensory and motor signals well explains how much its neural fluctuations
are suppressed by closed-loop optomotor behaviour. More generally we argue that
our results demonstrate the dependence of neural fluctuations, across the brain,
on closed-loop brain/body/environment interactions strongly supporting the idea
that brain function cannot be fully understood through open-loop approaches
alone.
PMID- 29342147
TI - Missed opportunities: Do states require screening of children for health
conditions that interfere with learning?
AB - METHODS: Investigators reviewed websites of state departments of health and
education, and legislation for all 50 states and DC. For states with mandated
screenings and a required form, investigators applied structured analysis to
assess HBL inclusion. RESULTS: No state mandated that schools require screening
for all 7 HBLs. Less than half (49%) required comprehensive school health
examinations and only 12 states plus DC required a specific form. Of these, 12 of
the forms required documentation of vision screening, 11 of hearing screening,
and 12 of dental screening. Ten forms asked about asthma and 9 required
documentation of lead testing. Seven asked about general well-being, emotional
problems, or mental health. None addressed hunger. When including states without
comprehensive school health examination requirements, the most commonly required
HBL screenings were for vision (80% of states; includes DC), hearing (75% of
states; includes DC) and dental (24% of state; includes DC). CONCLUSION: The lack
of state mandated requirements for regular student health screening represents a
missed opportunity to identify children with HBLs. Without state mandates,
accompanying comprehensive forms, and protocols, children continue to be at risk
of untreated health conditions that can undermine their success in school.
PMID- 29342148
TI - A strong summer phytoplankton bloom southeast of Vietnam in 2007, a transitional
year from El Nino to La Nina.
AB - Summer upwelling occurs frequently off the southeast Vietnam coast in the western
South China Sea (SCS), where summer phytoplankton blooms generally appear during
June-August. In this study, we investigate inter-annual variation of Ekman
pumping and offshore transport, and its modulation on summer blooms southeast of
Vietnam. The results indicate that there are low intensities of summer blooms in
El Nino years, under higher sea surface temperatures (SST) and weaker winds.
However, a different pattern of monthly chlorophyll a (Chl-a) blooms occurred in
summer of 2007, a transitional stage from El Nino to La Nina, with weak (strong)
wind and high (low) SST before (after) early July. There is a weak phytoplankton
bloom before July 2007 and a strong phytoplankton bloom after July 2007. The
abrupt change in the wind intensity may enhance the upwelling associated with
Ekman pumping and offshore Ekman transport, bringing more high-nutrient water
into the upper layer from the subsurface, and thus leading to an evident Chl-a
bloom in the region.
PMID- 29342149
TI - Low expression of IL-18 and IL-18 receptor in human skeletal muscle is associated
with systemic and intramuscular lipid metabolism-Role of HIV lipodystrophy.
AB - INTRODUCTION: Interleukin (IL)-18 is involved in regulation of lipid and glucose
metabolism. Mice lacking whole-body IL-18 signalling are prone to develop weight
gain and insulin resistance, a phenotype which is associated with impaired fat
oxidation and ectopic skeletal muscle lipid deposition. IL-18 mRNA is expressed
in human skeletal muscle but a role for IL-18 in muscle has not been identified.
Patients with HIV-infection and lipodystrophy (LD) are characterized by lipid and
glucose disturbances and increased levels of circulating IL-18. We hypothesized
that skeletal muscle IL-18 and IL-18 receptor (R) expression would be altered in
patients with HIV-lipodystrophy. DESIGN AND METHODS: Twenty-three HIV-infected
patients with LD and 15 age-matched healthy controls were included in a cross
sectional study. Biopsies from the vastus lateralis muscle were obtained and IL
18 and IL-18R mRNA expression were measured by real-time PCR and sphingolipids
(ceramides, sphingosine, sphingosine-1-Phosphate, sphinganine) were measured by
HPLC. Insulin resistance was assessed by HOMA and the insulin response during an
OGTT. RESULTS: Patients with HIV-LD had a 60% and 54% lower level of muscular IL
18 and IL-18R mRNA expression, respectively, compared to age-matched healthy
controls. Patients with HIV-LD had a trend towards increased levels of ceramide
(18.3+/-4.7 versus 14.8+/-3.0,p = 0.06) and sphingosine (0.41+/-0.13 versus
0.32+/-0.07, and lower level of sphinganine (p = 0.06). Low levels of muscle IL
18 mRNA correlated to high levels of ceramides (r = -0.31, p = 0.038) and
sphingosine-1P (r = -0.29, p = 0.046) in skeletal muscle, whereas such a
correlation was not found in healthy controls. Low expression of IL-18 mRNA in
skeletal muscle correlated to elevated concentration of circulating triglycerides
(Rp = -0.73, p<0.0001). Neither muscle expression of IL-18 mRNA or ceramide
correlated to parameters of insulin resistance. CONCLUSION: IL-18 (mRNA) in
skeletal muscle appears to be involved in the regulation of intramuscular lipid
metabolism and hypertriglyceridemia.
PMID- 29342150
TI - In vivo osteoconductivity of surface modified Ti-29Nb-13Ta-4.6Zr alloy with low
dissolution of toxic trace elements.
AB - Simulated Body Fluid (SBF) has served as a useful standard to check the
bioactivity of implant materials for years. However, it is not perfectly able to
imitate human serum; sometimes disparities between the SBF test and animal test
were confirmed. Therefore, to ensure the reliability of the results of the SBF
test obtained from our previous study, an animal study was performed to check
osteoconductivity of surface modified implant materials. Three types of solution
processes, hydrothermal (H), electrochemical (E), and hydrothermal
electrochemical (HE), were performed on the Ti-29Nb-13Ta-4.6Zr alloy (TNTZ) to
improve its bioactivity, and their bioactivities were measured in vivo using bone
implant contacts (BICs). BICs of the HE- and H-treated samples were significantly
higher than that of the control. Metal ion diffusion towards the bone was also
evaluated to examine the adverse effect of metal ions. No metal ion diffusion was
observed, indicating the safety of our solution processed implant materials.
PMID- 29342151
TI - CD8 signaling in microglia/macrophage M1 polarization in a rat model of cerebral
ischemia.
AB - Classical or M1 activity of microglia/macrophages has been described in several
neurodegenerative and brain inflammatory conditions and has also been linked to
expansion of ischemic injury in post-stroke brain. While different pathways of M1
polarization have been suggested to occur in the post-stroke brain, the precise
underlying mechanisms remain undefined. Using a transient middle cerebral artery
occlusion (MCAO) rat model, we showed a progressive M2 to M1 polarization in the
perilesional brain region with M1 cells becoming one of the dominant subsets by
day 4 post-stroke. Comparing key receptors involved in M1 polarization (CD8,
IFNgammaR, Clec4, FcgammaR, TLR3 and TLR4) and their signal transducers (Syk,
Stat1, Irf3, and Traf6) at the day 4 time point, we showed a strong upregulation
of CD8 along with SYK transducer in dissected perilesional brain tissue. We
further showed that CD8 expression in the post-stroke brain was associated with
activated (CD68+) macrophages and that progressive accumulation of CD8+CD68+
cells in the post-stroke brain coincided with increased iNOS (M1 marker) and
reduced Arg1 (M2 marker) expression on these cells. In vitro ligand-based
stimulation of the CD8 receptor caused increased iNOS expression and an enhanced
capacity to phagocytose E. coli particles; and interestingly, CD8 stimulation was
also able to repolarize IL4-treated M2 cells to an M1 phenotype. Our data suggest
that increased CD8 signaling in the post-stroke brain is primarily associated
with microglia/macrophages and can independently drive M1 polarization, and that
modulation of CD8 signaling could be a potential target to limit secondary post
stroke brain damage.
PMID- 29342152
TI - Do nursery habitats provide shelter from flow for juvenile fish?
AB - Juvenile fish nurseries are an essential life stage requirement for the
maintenance of many fish populations. With many inshore habitats globally in
decline, optimising habitat management by increasing our understanding of the
relationship between juvenile fish and nursery habitats may be a prudent
approach. Previous research on post-settlement snapper (Chrysophrys auratus) has
suggested that structure may provide a water flow refuge, allowing snapper to
access high water flow sites that will also have a high flux of their pelagic
prey. We investigated this hypothesis by describing how Artificial Seagrass Units
(ASUs) modified water flow while also using a multi-camera set up to quantify
snapper position in relation to this water flow environment. Horizontal water
flow was reduced on the down-current side of ASUs, but only at the height of the
seagrass canopy. While the highest abundance of snapper did occur down-current of
the ASUs, many snapper also occupied other locations or were too high in the
water column to receive any refuge from water flow. The proportion of snapper
within the water column was potentially driven by strategy to access zooplankton
prey, being higher on the up-current side of ASUs and on flood tides. It is
possible that post-settlement snapper alternate position to provide opportunities
for both feeding and flow refuging. An alternative explanation relates to an
observed interaction between post-settlement snapper and a predator, which
demonstrated that snapper can utilise habitat structure when threatened. The
nature of this relationship, and its overall importance in determining the value
of nursery habitats to post-settlement snapper remains an elusive next step.
PMID- 29342153
TI - The impact of optic nerve and related characteristics on disc area measurements
derived from different imaging techniques.
AB - PURPOSE: Optic nerve head (ONH) assessment and its interpretation in healthy
patients and those with glaucoma remains a pivotal topic specifically considering
rapid advancements in imaging technologies. We undertook a large-scale, mixed
cohort, comparative study to assess the correlation of optic disc measurements
between different imaging modalities and investigated the impact of patient and
disc associated parameters. METHODS: ONH sizes were obtained from one randomly
selected eye of each of 209 patients using stereophotography, confocal scanning
laser ophthalmoscopy and two different optical coherence tomographers (OCT).
Patient related data, glaucoma status and optic disc variables, specifically
oblique insertion, torsion, presence of beta PPA and spherical equivalent were
recorded. Measurements between imaging modalities were analysed using Pearson
correlation, linear regression analysis and Blend-Altman plots. Individual
variables were compared applying multivariate regression analysis, ANOVA and chi
square statistics was used to determine correlations between patient and clinical
characteristics. RESULTS: Absolute measurements significantly differed between
imaging modalities generally producing smaller measurements for OCT derived
measurements of Bruch's membrane opening (BMO). Pairwise correlations between
imaging modalities were between 0.83 and 0.93 for discs without myopia, oblique
insertion, or beta PPA. These features impacted on measurements for individual
modalities and consequently contributed to inconsistencies and variability.
CONCLUSION: In comparison to planimetry, OCT derived BMO measurements are more
variable in the presence of oblique insertion, beta PPA or magnification errors
due to myopia. Impact of these factors, however, differs between instruments and
needs to be considered to accurately interpret optic disc features in particular
within the context of glaucoma diagnosis.
PMID- 29342154
TI - Three unrelated and unexpected amino acids determine the susceptibility of the
interface cysteine to a sulfhydryl reagent in the triosephosphate isomerases of
two trypanosomes.
AB - Proteins with great sequence similarity usually have similar structure, function
and other physicochemical properties. But in many cases, one or more of the
physicochemical or functional characteristics differ, sometimes very
considerably, among these homologous proteins. To better understand how critical
amino acids determine quantitative properties of function in proteins, the
responsible residues must be located and identified. This can be difficult to
achieve, particularly in cases where multiple amino acids are involved. In this
work, two triosephosphate isomerases with very high similarity from two related
human parasites were used to address one such problem. We demonstrate that a
seventy-fold difference in the reactivity of an interface cysteine to the
sulfhydryl reagent methylmethane sulfonate in these two enzymes depends on three
amino acids located far away from this critical residue and which could not have
been predicted using other current methods. Starting from previous observations
with chimeric proteins involving these two triosephosphate isomerases, we
developed a strategy involving additive mutant enzymes and selected site directed
mutants to locate and identify the three amino acids. These three residues seem
to induce changes in the interface cysteine in reactivity by increasing (or
decreasing) its apparent pKa. Some enzymes with four to seven mutations also
exhibited altered reactivity. This study completes a strategy for identifying key
residues in the sequences of proteins that can have applications in future
protein structure-function studies.
PMID- 29342155
TI - Nanoscopic X-ray fluorescence imaging and quantification of intracellular key
elements in cryofrozen Friedreich's ataxia fibroblasts.
AB - Synchrotron radiation based nanoscopic X-ray fluorescence (SR nano-XRF) analysis
can visualize trace level elemental distribution in a fully quantitative manner
within single cells. However, in-air XRF analysis requires chemical fixation
modifying the cell's chemical composition. Here, we describe first nanoscopic XRF
analysis upon cryogenically frozen (-150 degrees C) fibroblasts at the ID16A-NI
'Nano-imaging' end-station located at the European Synchrotron Radiation Facility
(ESRF) in Grenoble (France). Fibroblast cells were obtained from skin biopsies
from control and Friedreich's ataxia (FRDA) patients. FRDA is an autosomal
recessive disorder with dysregulation of iron metabolism as a key feature. By
means of the X-ray Fundamental Parameter (FP) method, including absorption
correction of the ice layer deposited onto the fibroblasts, background-corrected
mass fraction elemental maps of P, S, Cl, K, Ca, Fe and Zn of entire cryofrozen
human fibroblasts were obtained. Despite the presence of diffracting
microcrystals in the vitreous ice matrix and minor sample radiation damage
effects, clusters of iron-rich hot-spots with similar mass fractions were found
in the cytoplasm of both control and FRDA fibroblasts. Interestingly, no
significant difference in the mean iron concentration was found in the cytoplasm
of FRDA fibroblasts, but a significant decrease in zinc concentration. This
finding might underscore metal dysregulation, beyond iron, in cells derived from
FRDA patients. In conclusion, although currently having slightly increased limits
of detection (LODs) compared to non-cryogenic mode, SR based nanoscopic XRF under
cryogenic sample conditions largely obliterates the debate on chemical sample
preservation and provides a unique tool for trace level elemental imaging in
single cells close to their native state with a superior spatial resolution of 20
nm.
PMID- 29342156
TI - Specialized attachment structure of the fish pathogenic oomycete Saprolegnia
parasitica.
AB - The secondary cysts of the fish pathogen oomycete Saprolegnia parasitica possess
bundles of long hooked hairs that are characteristic to this economically
important pathogenic species. Few studies have been carried out on elucidating
their specific role in the S. parasitica life cycle and the role they may have in
the infection process. We show here their function by employing several
strategies that focus on descriptive, developmental and predictive approaches.
The strength of attachment of the secondary cysts of this pathogen was compared
to other closely related species where bundles of long hooked hairs are absent.
We found that the attachment of the S. parasitica cysts was around three times
stronger than that of other species. The time sequence and influence of selected
factors on morphology and the number of the bundles of long hooked hairs
conducted by scanning electron microscopy study revealed that these are dynamic
structures. They are deployed early after encystment, i.e., within 30 sec of
zoospore encystment, and the length, but not the number, of the bundles steadily
increased over the encystment period. We also observed that the number and length
of the bundles was influenced by the type of substrate and encystment treatment
applied, suggesting that these structures can adapt to different substrates
(glass or fish scales) and can be modulated by different signals (i.e., protein
media, 50 mM CaCl2 concentrations, carbon particles). Immunolocalization studies
evidenced the presence of an adhesive extracellular matrix. The bioinformatic
analyses of the S. parasitica secreted proteins showed that there is a high
expression of genes encoding domains of putative proteins related to the
attachment process and cell adhesion (fibronectin and thrombospondin) coinciding
with the deployment stage of the bundles of long hooked hairs formation. This
suggests that the bundles are structures that might contribute to the adhesion of
the cysts to the host because they are composed of these adhesive proteins and/or
by increasing the surface of attachment of this extracellular matrix.
PMID- 29342157
TI - Timing of maternal death: Levels, trends, and ecological correlates using sibling
data from 34 sub-Saharan African countries.
AB - Millennium Development Goal 5 has not been universally achieved, particularly in
sub-Saharan Africa. Understanding whether maternal deaths occur during pregnancy,
childbirth, or puerperium is important to effectively plan maternal health
programs and allocate resources. Our main research objectives are to (1) describe
the proportions and rates of mortality for the antepartum, intrapartum, and
postpartum periods; (2) document how these trends vary by sub-region; and (3)
investigate ecological correlations between these rates and maternal care
interventions. We used data from the Demographic and Health Survey program, which
comprises 84 surveys from 34 sub-Saharan African countries conducted between 1990
and 2014. We calculated age-standardized maternal mortality rates and time
specific maternal mortality rates and proportions, and we assessed correlations
with maternal care coverage. We found high levels of maternal mortality in all
three periods. Time-specific maternal mortality rates varied by country and
region, with some showing an orderly decline in all three periods and others
exhibiting alarming increases in antepartum and postpartum mortality. Ecological
analysis showed that antenatal care coverage was significantly associated with
low antepartum mortality, whereas the presence of a skilled attendant at
childbirth was significantly associated with low postpartum mortality. In sub
Saharan Africa, maternal deaths occur at high rates in all three risk periods,
and vary substantially by country and region. The provision of maternal care is a
predictor of time-specific maternal mortality. These results confirm the need for
country-specific interventions during the continuum of care to achieve the global
commitment to eliminating preventable maternal mortality.
PMID- 29342158
TI - Real-time community detection in full social networks on a laptop.
AB - For a broad range of research and practical applications it is important to
understand the allegiances, communities and structure of key players in society.
One promising direction towards extracting this information is to exploit the
rich relational data in digital social networks (the social graph). As global
social networks (e.g., Facebook and Twitter) are very large, most approaches make
use of distributed computing systems for this purpose. Distributing graph
processing requires solving many difficult engineering problems, which has lead
some researchers to look at single-machine solutions that are faster and easier
to maintain. In this article, we present an approach for analyzing full social
networks on a standard laptop, allowing for interactive exploration of the
communities in the locality of a set of user specified query vertices. The key
idea is that the aggregate actions of large numbers of users can be compressed
into a data structure that encapsulates the edge weights between vertices in a
derived graph. Local communities can be constructed by selecting vertices that
are connected to the query vertices with high edge weights in the derived graph.
This compression is robust to noise and allows for interactive queries of local
communities in real-time, which we define to be less than the average human
reaction time of 0.25s. We achieve single-machine real-time performance by
compressing the neighborhood of each vertex using minhash signatures and
facilitate rapid queries through Locality Sensitive Hashing. These techniques
reduce query times from hours using industrial desktop machines operating on the
full graph to milliseconds on standard laptops. Our method allows exploration of
strongly associated regions (i.e., communities) of large graphs in real-time on a
laptop. It has been deployed in software that is actively used by social network
analysts and offers another channel for media owners to monetize their data,
helping them to continue to provide free services that are valued by billions of
people globally.
PMID- 29342159
TI - Prediction of novel target genes and pathways involved in bevacizumab-resistant
colorectal cancer.
AB - Bevacizumab combined with cytotoxic chemotherapy is the backbone of metastatic
colorectal cancer (mCRC) therapy; however, its treatment efficacy is hampered by
therapeutic resistance. Therefore, understanding the mechanisms underlying
bevacizumab resistance is crucial to increasing the therapeutic efficacy of
bevacizumab. The Gene Expression Omnibus (GEO) database (dataset, GSE86525) was
used to identify the key genes and pathways involved in bevacizumab-resistant
mCRC. The GEO2R web tool was used to identify differentially expressed genes
(DEGs). Functional and pathway enrichment analyses of the DEGs were performed
using the Database for Annotation, Visualization, and Integrated
Discovery(DAVID). Protein-protein interaction (PPI) networks were established
using the Search Tool for the Retrieval of Interacting Genes/Proteins
database(STRING) and visualized using Cytoscape software. A total of 124 DEGs
were obtained, 57 of which upregulated and 67 were downregulated. PPI network
analysis showed that seven upregulated genes and nine downregulated genes
exhibited high PPI degrees. In the functional enrichment, the DEGs were mainly
enriched in negative regulation of phosphate metabolic process and positive
regulation of cell cycle process gene ontologies (GOs); the enriched pathways
were the phosphoinositide 3-kinase-serine/threonine kinase signaling pathway,
bladder cancer, and microRNAs in cancer. Cyclin-dependent kinase inhibitor
1A(CDKN1A), toll-like receptor 4 (TLR4), CD19 molecule (CD19), breast cancer 1,
early onset (BRCA1), platelet-derived growth factor subunit A (PDGFA), and matrix
metallopeptidase 1 (MMP1) were the DEGs involved in the pathways and the PPIs.
The clinical validation of the DEGs in mCRC (TNM clinical stages 3 and 4)
revealed that high PDGFA expression levels were associated with poor overall
survival, whereas high BRCA1 and MMP1 expression levels were associated with
favorable progress free survival(PFS). The identified genes and pathways can be
potential targets and predictors of therapeutic resistance and prognosis in
bevacizumab-treated patients with mCRC.
PMID- 29342160
TI - Expression of the lux genes in Streptococcus pneumoniae modulates pilus
expression and virulence.
AB - Bioluminescence has been harnessed for use in bacterial reporter systems and for
in vivo imaging of infection in animal models. Strain Xen35, a bioluminescent
derivative of Streptococcus pneumoniae serotype 4 strain TIGR4 was previously
constructed for use for in vivo imaging of infections in animal models. We have
shown that strain Xen35 is less virulent than its parent TIGR4 and that this is
associated with the expression of the genes for bioluminescence. The expression
of the luxA-E genes in the pneumococcus reduces virulence and down regulates the
expression of the pneumococcal pilus.
PMID- 29342161
TI - Association between circulating levels of sex steroid hormones and esophageal
adenocarcinoma in the FINBAR Study.
AB - BACKGROUND: Esophageal adenocarcinoma (EA) is characterized by a strong male
predominance. Sex steroid hormones have been hypothesized to underlie this sex
disparity, but no population-based study to date has examined this potential
association. METHODS: Using mass spectrometry and ELISA, we quantitated sex
steroid hormones and sex hormone binding globulin, respectively, in plasma from
males- 172 EA cases and 185 controls-within the Factors Influencing the
Barrett/Adenocarcinoma Relationship (FINBAR) Study, a case-control investigation
conducted in Northern Ireland and Ireland. Multivariable adjusted logistic
regression was used to calculate odds ratios (ORs) and 95% confidence intervals
(CIs) for associations between circulating hormones and EA. RESULTS: Higher
androgen:estrogen ratio metrics were associated with increased odds of EA (e.g.,
testosterone:estradiol ratio ORQ4 v. Q1 = 2.58, 95%CI = 1.23-5.43; Ptrend =
0.009). All estrogens and androgens were associated with significant decreased
odds of EA. When restricted to individuals with minimal to no decrease in body
mass index, the size of association for the androgen:estrogen ratio was not
greatly altered. CONCLUSIONS: This first study of sex steroid hormones and EA
provides tentative evidence that androgen:estrogen balance may be a factor
related to EA. Replication of these findings in prospective studies is needed to
enhance confidence in the causality of this effect.
PMID- 29342162
TI - Comparison of diagnostic methods to detect Histoplasma capsulatum in serum and
blood samples from AIDS patients.
AB - BACKGROUND: Although early and rapid detection of histoplasmosis is essential to
prevent morbidity and mortality, few diagnostic tools are available in resource
limited areas, especially where it is endemic and HIV/AIDS is also epidemic.
Thus, we compared conventional and molecular methods to detect Histoplasma
capsulatum in sera and blood from HIV/AIDS patients. METHODOLOGY: We collected a
total of 40 samples from control volunteers and patients suspected of
histoplasmosis, some of whom were also infected with other pathogens. Samples
were then analyzed by mycological, serological, and molecular methods, and
stratified as histoplasmostic with (group I) or without AIDS (group II),
uninfected (group III), and infected with HIV and other pathogens only (group
IV). All patients were receiving treatment for histoplasmosis and other
infections at the time of sample collection. RESULTS: Comparison of conventional
methods with nested PCR using primers against H. capsulatum 18S rRNA (HC18S),
5.8S rRNA ITS (HC5.8S-ITS), and a 100 kDa protein (HC100) revealed that
sensitivity against sera was highest for PCR with HC5.8S-ITS, followed by
immunoblotting, double immunodiffusion, PCR with HC18S, and PCR with HC100.
Specificity was equally high for double immunodiffusion, immunoblotting and PCR
with HC100, followed for PCR with HC18S and HC5.8-ITS. Against blood, sensitivity
was highest for PCR with HC5.8S-ITS, followed by PCR with HC18S, Giemsa staining,
and PCR with HC100. Specificity was highest for Giemsa staining and PCR with
HC100, followed by PCR with HC18S and HC5.8S-ITS. PCR was less efficient in
patients with immunodeficiency due to HIV/AIDS and/or related diseases.
CONCLUSION: Molecular techniques may detect histoplasmosis even in cases with
negative serology and mycology, potentially enabling early diagnosis.
PMID- 29342163
TI - Doxylamine-pyridoxine for nausea and vomiting of pregnancy randomized placebo
controlled trial: Prespecified analyses and reanalysis.
AB - BACKGROUND: Doxylamine-pyridoxine is recommended as a first line treatment for
nausea and vomiting during pregnancy and it is commonly prescribed. We re
analysed the findings of a previously reported superiority trial of doxylamine
pyridoxine for the treatment of nausea and vomiting during pregnancy using the
clinical study report obtained from Health Canada. METHODS AND FINDINGS: We re
analysed individual level data for a parallel arm randomized controlled trial
that was conducted in six outpatient obstetrical practices in the United States.
Pregnant women between 7 and 14 weeks of gestation with moderate nausea and
vomiting of pregnancy symptoms. The active treatment was a tablet containing both
doxylamine 10 mg and pyridoxine 10 mg taken between 2 and 4 times per day for 14
days depending on symptoms. The control was an identical placebo tablet taken
using the same instructions. The primary outcome measure was improvement in
nausea and vomiting of symptoms scores using the 13-point pregnancy unique
quantification of emesis scale between baseline and 14 days using an ANCOVA. 140
participants were randomized into each group. Data for 131 active treatment
participants and 125 control participants were analysed. On the final day of the
trial, 101 active treatment participants and 86 control participants provided
primary outcome measures. There was greater improvement in symptoms scores with
doxylamine-pyridoxine compared with placebo (0.73 points; 95% CI 0.21 to 1.25)
when last observation carried forward imputation was used for missing data but
the difference is not statistically significant using other approaches to missing
data (e.g. 0.38; 95% CI -0.08 to 0.84 using complete data). CONCLUSIONS: There is
a trend towards efficacy for nausea and vomiting symptoms with doxylamine
pyridoxine compared with placebo but the statistical significance of the
difference depends on the method of handling missing data and the magnitude of
the difference suggests that there is no clinically important benefit employing
the prespecified minimal clinically important difference or "expected difference"
of 3 points. TRIAL REGISTRATION: Clinical Trial NCT00614445.
PMID- 29342164
TI - Environmental dust inhalation in the European badger (Meles meles): Systemic
distribution of silica-laden macrophages, pathological changes, and association
with Mycobacterium bovis infection status.
AB - Chronic inhalation of crystalline silica and silicates may lead to severe lung
disease in humans, termed silicosis. The disease is an occupational health
concern in miners and related professions worldwide. Silicosis is also a strong
risk factor for tuberculosis in humans. Due to its subterranean lifestyle, the
European badger (Meles meles) is continuously exposed to environmental dust,
while this species is also susceptible to tuberculosis, caused by Mycobacterium
bovis. To date, a thorough investigation of mineral dust retention and its
possible implication as a risk factor for mycobacterial infection in badgers has
not been performed. The aims of this retrospective histological study were (1) to
describe the systemic tissue distribution of silica-laden macrophages (SLMs) in
badgers; (2) to compare the amount of SLMs in tissues of badgers of differing M.
bovis infection status, pulmonary SLM burden and age; and (3) to assess whether
inflammation was associated with SLMs. We assessed lung, lymph nodes, liver and
spleen of 60 wild-caught badgers of known M. bovis infection status for the
presence of SLMs using polarizing light microscopy. SLMs were consistently
present within the lungs and were widely distributed throughout the lymphatic
system. No inflammatory reaction to SLMs, as occurs in human silicosis, was
observed in any tissue. Distribution and amount of SLMs were similar between M.
bovis positive and negative badgers, and we were not able to show an association
between the amount of SLMs and M. bovis infection status. The amount of SLMs
within intra- and extrathoracic lymph nodes was positively associated with the
amount of pulmonary SLMs, and with age. This is the first report of substantial
and systemic tissue retention of mineral dust particles in a mammalian species
lacking associated chronic inflammation (i.e. silicosis). We further highlight
different pathogenetic mechanisms underlying silicosis and benign SLM
accumulations following siliceous dust inhalation.
PMID- 29342165
TI - Increased colon cancer risk after severe Salmonella infection.
AB - BACKGROUND: Colon cancer constitutes one of the most frequent malignancies.
Previous studies showed that Salmonella manipulates host cell signaling pathways
and that Salmonella Typhimurium infection facilitates colon cancer development in
genetically predisposed mice. This epidemiological study examined whether severe
Salmonella infection, usually acquired from contaminated food, is associated with
increased colon cancer risk in humans. METHODS AND FINDINGS: We performed a
nationwide registry-based study to assess colon cancer risk after diagnosed
Salmonella infection. National infectious disease surveillance records (1999
2015) for Dutch residents aged >=20 years when diagnosed with salmonellosis (n =
14,264) were linked to the Netherlands Cancer Registry. Salmonella-infected
patients were laboratory-confirmed under medical consultation after 1-2 weeks of
illness. These datasets also contained information on Salmonella serovar and type
of infection. Colon cancer risk (overall and per colon subsite) among patients
with a diagnosed Salmonella infection was compared with expected colon cancer
risk in the general population. Data from the nationwide registry of histo- and
cytopathology (PALGA) and Statistics Netherlands (CBS) allowed assessing
potential effects of age, gender, latency, socioeconomic status, genetic
predisposition, inflammatory bowel disease (IBD), and tumor features. We found
that compared to the general population, colon cancer risk was significantly
increased (standardized incidence ratio [SIR] 1.54; 95%CI 1.09-2.10) among
patients with Salmonella infection diagnosed <60 years of age. Such increased
risk concerned specifically the ascending/transverse colon (SIR 2.12; 95%CI 1.38
3.09) after S. Enteritidis infection (SIR 2.97; 95%CI 1.73-4.76). Salmonellosis
occurred more frequently among colon cancer patients with pre-infectious IBD, a
known risk factor for colon cancer. Colon tumors of patients with a history of
Salmonella infection were mostly of low grade. CONCLUSIONS: Patients diagnosed
with severe salmonellosis have an increased risk of developing cancer in the
ascending/transverse parts of the colon. This risk concerns particularly S.
Enteritidis infection, suggesting a contribution of this major foodborne pathogen
to colon cancer development.
PMID- 29342166
TI - Effects of vitamin D on insulin resistance and myosteatosis in diet-induced obese
mice.
AB - Epidemiological studies pointed out to a strong association between vitamin D
deficiency and type 2 diabetes prevalence. However, the role of vitamin D
supplementation in the skeletal muscle, a tissue that play a crucial role in the
maintenance of glucose homeostasis, has been scarcely investigated so far. On
this basis, this study aimed to evaluate the effect of vitamin D supplementation
in a murine model of diet-induced insulin resistance with particular attention to
the effects evoked on the skeletal muscle. Male C57BL/6J mice (n = 40) were fed
with a control or a High Fat-High Sugar (HFHS) diet for 4 months. Subsets of
animals were treated for 2 months with vitamin D (7 MUg.kg-1, i.p. three
times/week). HFHS diet induced body weight increase, hyperglycemia and impaired
glucose tolerance. HFHS animals showed an impaired insulin signaling and a marked
fat accumulation in the skeletal muscle. Vitamin D reduced body weight and
improved systemic glucose tolerance. In addition, vitamin D restored the impaired
muscle insulin signaling and reverted myosteatosis evoked by the diet. These
effects were associated to decreased activation of NF-kappaB and lower levels of
TNF-alpha. Consistently, a significantly decreased activation of the SCAP/SREBP
lipogenic pathway and lower levels of CML protein adducts and RAGE expression
were observed in skeletal muscle of animals treated with vitamin D. Collectively,
these data indicate that vitamin D-induced selective inhibition of signaling
pathways (including NF-kappaB, SCAP/SREBP and CML/RAGE cascades) within the
skeletal muscle significantly contributed to the beneficial effects of vitamin D
supplementation against diet-induced metabolic derangements.
PMID- 29342167
TI - Effects of ammonium-based ionic liquids and 2,4-dichlorophenol on the
phospholipid fatty acid composition of zebrafish embryos.
AB - Ionic liquids consisting of a combination of herbicidal anions with a quaternary
ammonium cation act as efficient herbicides, which are under consideration to be
used in the agriculture. In the present study, we used embryos of the zebrafish
(Danio rerio) as a model to assess the toxic potential of ammonium-based ionic
liquids for aquatic organisms. As we assumed interference of the partially
hydrophobic ionic liquid cation with lipids, we investigated the adaptation
response in the lipid composition of the zebrafish embryos, triggered by the
ionic compound. Therefore, the impact of ammonium-based ionic liquids with
different lengths of the alkyl chain ([C6,C6,C1,C1N][Br], [C8,C8,C1,C1N][Br]) on
the phospholipid fatty acid (PLFA) profile of zebrafish embryos up to 72 hours
post fertilization (hpf) was examined. Furthermore, the changes in the
unsaturation index (UI) of PLFAs, as the sum parameter of membrane fluidity in
eukaryotic cells, were presented. The PLFA's UI in the zebrafish embryos upon
exposure to quaternary ammonium salts was compared to the UI of the embryos upon
exposure to nonionic 2,4-dichlorophenol, which has a similar hydrophobicity but
is structurally different to [C8,C8,C1,C1N][Br]. It was shown that for ammonium
based ionic liquid precursors non-specific mode of action occurs and the toxic
effect on lipid composition of zebrafish embryos can be well predicted based on
chemical properties, like hydrophobicity. Furthermore, the changes in PLFAs,
expressed by the UI, can be useful to study toxic effects of organic
contamination. However, for zebrafish embryos, after ionic liquids and 2,4-DCP
exposure, the changes were observed at high lethal concentrations, which caused
the incidence of lethality of 30 and 50% of a group of test animals.
PMID- 29342168
TI - Reduction in Musca domestica fecundity by dsRNA-mediated gene knockdown.
AB - House flies (Musca domestica) are worldwide agricultural pests with estimated
control costs at $375 million annually in the U.S. Non-target effects and
widespread resistance challenge the efficacy of traditional chemical control.
Double stranded RNA (dsRNA) has been suggested as a biopesticide for M. domestica
but a phenotypic response due to the induction of the RNAi pathway has not been
demonstrated in adults. In this study female house flies were injected with dsRNA
targeting actin-5C or ribosomal protein (RP) transcripts RPL26 and RPS6. Ovaries
showed highly reduced provisioning and clutch reductions of 94-99% in RP dsRNA
treated flies but not in actin-5C or GFP treated flies. Gene expression levels
were significantly and specifically reduced in dsRNA injected groups but remained
unchanged in the control dsGFP treated group. Furthermore, injections with an
Aedes aegypti conspecific dsRNA designed against RPS6 did not impact fecundity,
demonstrating species specificity of the RNAi response. Analysis of M. domestica
tissues following RPS6 dsRNA injection showed significant reduction of transcript
levels in the head, thorax, and abdomen but increased expression in ovarian
tissues. This study demonstrates that exogenous dsRNA is specifically effective
and has potential efficacy as a highly specific biocontrol intervention in adult
house flies. Further work is required to develop effective methods for delivery
of dsRNA to adult flies.
PMID- 29342169
TI - Interactions between the invasive Burmese python, Python bivittatus Kuhl, and the
local mosquito community in Florida, USA.
AB - The Burmese python, Python bivittatus Kuhl, is a well-established invasive
species in the greater Everglades ecosystem of southern Florida, USA. Most
research on its ecological impacts focuses on its role as a predator and its
trophic interactions with native vertebrate species, particularly mammals. Beyond
predation, there is little known about the ecological interactions between P.
bivittatus and native faunal communities. It is likely that established
populations of P. bivittatus in southern Florida serve as hosts for native
mosquito communities. To test this concept, we used mitochondrial cytochrome c
oxidase subunit I DNA barcoding to determine the hosts of blood fed mosquitoes
collected at a research facility in northern Florida where captive P. bivittatus
and Argentine black and white tegu, Salvator merianae (Dumeril and Bibron), are
maintained in outdoor enclosures, accessible to local mosquitoes. We recovered
python DNA from the blood meals of three species of Culex mosquitoes: Culex
erraticus (Dyar and Knab), Culex quinquefasciatus Say, and Culex pilosus (Dyar
and Knab). Culex erraticus conclusively (P = 0.001; Fisher's Exact Test) took
more blood meals from P. bivittatus than from any other available host. While the
majority of mosquito blood meals in our sample were derived from P. bivittatus,
only one was derived from S. merianae. These results demonstrate that local
mosquitoes will feed on invasive P. bivittatus, a recently introduced host. If
these interactions also occur in southern Florida, P. bivittatus may be involved
in the transmission networks of mosquito-vectored pathogens. Our results also
illustrate the potential of detecting the presence of P. bivittatus in the field
through screening mosquito blood meals for their DNA.
PMID- 29342170
TI - Determination of 2,4-Dichlorophenoxyacetic acid (2,4-D) in rat serum for
pharmacokinetic studies with a simple HPLC method.
AB - 2,4-Dichlorophenoxyacetic acid (2,4-D) is a chlorophenoxy herbicide used
worldwide. We describe a high-performance liquid chromatography (HPLC) method
with UV detection for the determination of 2,4-D in female and male rat serum.
This allows to observe the change of serum 2,4-D concentration in rats with time
and its pharmacokinetics characteristics with a simple, rapid, optimized and
validated method. The serum samples are pretreated and introduced into the HPLC
system. The analytes are separated in a XDB-C18 column with a mobile phase of
acetonitrile (solvent A) and 0.02 M ammonium acetate (containing 0.1% formic
acid) (solvent B) using a gradient elution at a flow rate of 1.0 mL/min. The
wavelength for UV detection was set at 230 nm. Calibration curve for 2,4-D was
constructed over a range of 0.1-400 mg/L. The method was successfully applied to
study the pharmacokinetics of 2,4-D in rats in this study. After oral
administration of 300 mg/kg and 60 mg/kg 2,4-D, the mean Cmax values were 601.9
and 218.4 mg/L, the AUC0->infinity values were 23,722 and 4,127 mg*h/L and the
clearance (Cl) were 1.10 and 0.02 L/(h*kg), respectively. The developed method
was found to be specific, precise, reproducible and rapid.
PMID- 29342171
TI - Health behavior associated with liver enzymes among obese Korean adolescents,
2009-2014.
AB - AIMS: Obesity is major risk factor for liver health. This study aimed to clarify
whether specific health behaviors were associated with liver function in obese
adolescents in Korea. METHODS: Based on national school health examination data
from 2009 to 2014, 25,142 obese or overweight students were examined for
aspartate transaminase and alanine transaminase levels, and health behaviors.
Multiple logistic regression was used to calculate the odds ratio for liver
enzyme elevation. RESULTS: Subjects who thought of themselves as "very fat" had a
1.6 times higher odds ratio for liver enzyme elevations than those who thought of
themselves as "normal." Those who consumed fast food 3 to 5 times weekly had 1.3
times higher odds ratio (OR = 1.27, 95% confidence interval = 1.05-1.54) for the
elevation of ALT than those who did not consume fast food. Those who took sugar
sweetened beverage 3 to 5 times weekly had 1.2 times higher odds ratio (OR =
1.24, 95% confidence interval = 1.07-1.42) for the elevation of ALT than those
who did not take it. Those who played computer game more than 2 hours a day
showed 1.1 times higher odds ratio (OR = 1.10, 95% confidence interval = 1.01
1.21) for the elevation of ALT than those who did not. CONCLUSIONS: Specific food
item and its frequency of consumption were identified for the positive and
negative association with the elevation of liver enzymes. Self-image of body
shape, sleeping time and need of help for alcohol or smoking problems also showed
substantial association with the elevation.
PMID- 29342172
TI - Driving factors of retention in care among HIV-positive MSM and transwomen in
Indonesia: A cross-sectional study.
AB - Little is known about the prevalence of and factors that influence retention in
HIV-related care among Indonesian men who have sex with men (MSM) and transgender
women (transwomen, or waria in Indonesian term). Therefore, we explored the
driving factors of retention in care among HIV-positive MSM and waria in
Indonesia. This cross-sectional study involved 298 self-reported HIV-positive MSM
(n = 165) and waria (n = 133). Participants were recruited using targeted
sampling and interviewed using a structured questionnaire. We applied a four-step
model building process using multivariable logistic regression to examine how
sociodemographic, predisposing, enabling, and reinforcing factors were associated
with retention in care. Overall, 78.5% of participants were linked to HIV care
within 3 months after diagnosis or earlier, and 66.4% were adequately retained in
care (at least one health care visit every three months once a person is
diagnosed with HIV). Being on antiretroviral therapy (adjusted odds ratio [AOR] =
6.00; 95% confidence interval [CI]: 2.93-12.3), using the Internet to find HIV
related information (AOR = 2.15; 95% CI: 1.00-4.59), and having medical insurance
(AOR = 2.84; 95% CI: 1.27-6.34) were associated with adequate retention in care.
Involvement with an HIV-related organization was associated negatively with
retention in care (AOR = 0.47; 95% CI: 0.24-0.95). Future interventions should
increase health insurance coverage and utilize the Internet to help MSM and waria
to remain in HIV-related care, thereby assisting them in achieving viral
suppression.
PMID- 29342173
TI - Hormone induced differential transcriptome analysis of Sertoli cells during
postnatal maturation of rat testes.
AB - Sertoli cells (Sc) are unique somatic cells of testis that are the target of both
FSH and testosterone (T) and regulate spermatogenesis. Although Sc of neonatal
rat testes are exposed to high levels of FSH and T, robust differentiation of
spermatogonial cells becomes conspicuous only after 11-days of postnatal age. We
have demonstrated earlier that a developmental switch in terms of hormonal
responsiveness occurs in rat Sc at around 12 days of postnatal age during the
rapid transition of spermatogonia A to B. Therefore, such "functional maturation"
of Sc, during pubertal development becomes prerequisite for the onset of
spermatogenesis. However, a conspicuous difference in robust hormone (both T and
FSH) induced gene expression during the different phases of Sc maturation
restricts our understanding about molecular events necessary for the
spermatogenic onset and maintenance. Here, using microarray technology, we for
the first time have compared the differential transcriptional profile of Sc
isolated and cultured from immature (5 days old), maturing (12 days old) and
mature (60 days old) rat testes. Our data revealed that immature Sc express genes
involved in cellular growth, metabolism, chemokines, cell division, MAPK and Wnt
pathways, while mature Sc are more specialized expressing genes involved in
glucose metabolism, phagocytosis, insulin signaling and cytoskeleton structuring.
Taken together, this differential transcriptome data provide an important
resource to reveal the molecular network of Sc maturation which is necessary to
govern male germ cell differentiation, hence, will improve our current
understanding of the etiology of some forms of idiopathic male infertility.
PMID- 29342174
TI - Preference evaluation of ground beef by untrained subjects with three levels of
finely textured beef.
AB - After receiving bad publicity in 2012 and being removed from many ground beef
products, finely textured beef (referred to as 'pink slime' by some) is making a
comeback. Some of its proponents argue that consumers prefer ground beef
containing finely textured beef, but no objective scientific party has tested
this claim-that is the purpose of the present study. Over 200 untrained subjects
participated in a sensory analysis in which they tasted one ground beef sample
with no finely textured beef, another with 15% finely textured beef (by weight),
and another with more than 15%. Beef with 15% finely textured beef has an
improved juiciness (p < 0.01) and tenderness (p < 0.01) quality. However,
subjects rate the flavor-liking and overall likeability the same regardless of
the finely textured beef content. Moreover, when the three beef types are
consumed as part of a slider (small hamburger), subjects are indifferent to the
level of finely textured beef.
PMID- 29342176
TI - The "handedness" of language: Directional symmetry breaking of sign usage in
words.
AB - Language, which allows complex ideas to be communicated through symbolic
sequences, is a characteristic feature of our species and manifested in a
multitude of forms. Using large written corpora for many different languages and
scripts, we show that the occurrence probability distributions of signs at the
left and right ends of words have a distinct heterogeneous nature. Characterizing
this asymmetry using quantitative inequality measures, viz. information entropy
and the Gini index, we show that the beginning of a word is less restrictive in
sign usage than the end. This property is not simply attributable to the use of
common affixes as it is seen even when only word roots are considered. We use the
existence of this asymmetry to infer the direction of writing in undeciphered
inscriptions that agrees with the archaeological evidence. Unlike traditional
investigations of phonotactic constraints which focus on language-specific
patterns, our study reveals a property valid across languages and writing
systems. As both language and writing are unique aspects of our species, this
universal signature may reflect an innate feature of the human cognitive
phenomenon.
PMID- 29342175
TI - Immunocontraceptive target repertoire defined by systematic identification of
sperm membrane alloantigens in a single species.
AB - Sperm competence in animal fertilization requires the collective activities of
numerous sperm-specific proteins that are typically alloimmunogenic in females.
Consequently, sperm membrane alloantigens are potential targets for
contraceptives that act by blocking the proteins' functions in gamete
interactions. Here we used a targeted proteomics approach to identify the major
alloantigens in swine sperm membranes and lipid rafts, and thereby systematically
defined the repertoire of these sperm-specific proteins in a single species.
Gilts with high alloantibody reactivity to proteins in sperm membranes or lipid
rafts produced fewer offspring (73% decrease) than adjuvant-only or nonimmune
control animals. Alloantisera recognized more than 20 potentially unique sperm
membrane proteins and five sperm lipid raft proteins resolved on two-dimensional
immunoblots with or without prior enrichment by anion exchange chromatography.
Dominant sperm membrane alloantigens identified by mass spectrometry included the
ADAMs fertilin alpha, fertilin beta, and cyritestin. Less abundant alloantigens
included ATP synthase F1 beta subunit, myo-inositol monophosphatase-1, and
zymogen granule membrane glycoprotein-2. Immunodominant sperm lipid raft
alloantigens included SAMP14, lymphocyte antigen 6K, and the epididymal sperm
protein E12. Of the fifteen unique membrane alloantigens identified, eleven were
known sperm-specific proteins with uncertain functions in fertilization, and four
were not previously suspected to exist as sperm-specific isoforms. De novo
sequences of tryptic peptides from sperm membrane alloantigen "M6" displayed no
evident homology to known proteins, so is a newly discovered sperm-specific gene
product in swine. We conclude that alloimmunizing gilts with sperm membranes or
lipid rafts evokes formation of antibodies to a relatively small number of
dominant alloantigens that include known and novel sperm-specific proteins with
possible functions in fertilization and potential utility as targets for
immunocontraception.
PMID- 29342177
TI - A new fluorescent dye accumulation assay for parallel measurements of the ABCG2,
ABCB1 and ABCC1 multidrug transporter functions.
AB - ABC multidrug transporters are key players in cancer multidrug resistance and in
general xenobiotic elimination, thus their functional assays provide important
tools for research and diagnostic applications. In this study we have examined
the potential interactions of three key human ABC multidrug transporters with
PhenGreen diacetate (PGD), a cell permeable fluorescent metal ion indicator. The
non-fluorescent, hydrophobic PGD rapidly enters the cells and, after cleavage by
cellular esterases, in the absence of quenching metal ions, PhenGreen (PG)
becomes highly fluorescent. We found that in cells expressing functional ABCG2,
ABCB1, or ABCC1 transporters, cellular PG fluorescence is strongly reduced. This
fluorescence signal in the presence of specific transporter inhibitors is
increased to the fluorescence levels in the control cells. Thus the PG
accumulation assay is a new, unique tool for the parallel determination of the
function of the ABCG2, ABCB1, and ABCC1 multidrug transporters. Since PG has very
low cellular toxicity, the PG accumulation assay also allows the selection,
separation and culturing of selected cell populations expressing either of these
transporters.
PMID- 29342178
TI - Chaos and multi-scroll attractors in RCL-shunted junction coupled Jerk circuit
connected by memristor.
AB - In this paper, a new four-variable dynamical system is proposed to set chaotic
circuit composed of memristor and Josephson junction, and the dependence of
chaotic behaviors on nonlinearity is investigated. A magnetic flux-controlled
memristor is used to couple with the RCL-shunted junction circuit, and the
dynamical behaviors can be modulated by changing the coupling intensity between
the memristor and the RCL-shunted junction. Bifurcation diagram and Lyapunov
exponent are calculated to confirm the emergence of chaos in the improved
dynamical system. The outputs and dynamical behaviors can be controlled by the
initial setting and external stimulus as well. As a result, chaos can be
suppressed and spiking occurs in the sampled outputs under negative feedback,
while applying positive feedback type via memristor can be effective to trigger
chaos. Furthermore, it is found that the number of multi-attractors in the Jerk
circuit can be modulated when memristor coupling is applied on the circuit. These
results indicate that memristor coupling can be effective to control chaotic
circuits and it is also useful to reproduce dynamical behaviors for neuronal
activities.
PMID- 29342179
TI - The polymethoxy flavonoid sudachitin suppresses inflammatory bone destruction by
directly inhibiting osteoclastogenesis due to reduced ROS production and MAPK
activation in osteoclast precursors.
AB - Inflammatory bone diseases, including rheumatoid arthritis, periodontitis and
peri-implantitis, are associated not only with the production of inflammatory
cytokines but also with local oxidative status, which is defined by intracellular
reactive oxygen species (ROS). Osteoclast differentiation has been reported to be
related to increased intracellular ROS levels in osteoclast lineage cells.
Sudachitin, which is a polymethoxyflavone derived from Citrus sudachi, possesses
antioxidant properties and regulates various functions in mammalian cells.
However, the effects of sudachitin on inflammatory bone destruction and
osteoclastogenesis remain unknown. In calvaria inflamed by a local
lipopolysaccharide (LPS) injection, inflammation-induced bone destruction and the
accompanying elevated expression of osteoclastogenesis-related genes were reduced
by the co-administration of sudachitin and LPS. Moreover, sudachitin inhibited
osteoclast formation in cultures of isolated osteoblasts and osteoclast
precursors. However, sudachitin rather increased the expression of receptor
activator of NF-kappaB ligand (RANKL), which is an important molecule triggering
osteoclast differentiation, and the mRNA ratio of RANKL/osteoprotegerin that is a
decoy receptor for RANKL, in the isolated osteoblasts, suggesting the presence of
additional target cells. When osteoclast formation was induced from osteoclast
precursors derived from bone marrow cells in the presence of soluble RANKL and
macrophage colony-stimulating factor, sudachitin inhibited osteoclastogenesis
without influencing cell viability. Consistently, the expression of osteoclast
differentiation-related molecules including c-fos, NFATc1, cathepsin K and
osteoclast fusion proteins such as DC-STAMP and Atp6v0d2 was reduced by
sudachitin. In addition, sudachitin decreased activation of MAPKs such as Erk and
JNK and the ROS production evoked by RANKL in osteoclast lineage cells. Our
findings suggest that sudachitin is a useful agent for the treatment of anti
inflammatory bone destruction.
PMID- 29342180
TI - Increased prevalence of pregnancy and comparative risk of program attrition among
individuals starting HIV treatment in East Africa.
AB - BACKGROUND: The World Health Organization now recommends initiating all pregnant
women on life-long antiretroviral therapy (ART), yet there is limited information
about the characteristics and program outcomes of pregnant women already on ART
in Africa. Our hypothesis was that pregnant women comprised an increasing
proportion of those starting ART, and that sub-groups of these women were at
higher risk for program attrition. METHODS AND FINDINGS: We used the
International Epidemiology Databases to Evaluate AIDS- East Africa (IeDEA-EA) to
conduct a retrospective cohort study including HIV care and treatment programs in
Kenya, Uganda, and Tanzania. The cohort consecutively included HIV-infected
individuals 13 years or older starting ART 2004-2014. We examined trends over
time in the proportion pregnant, their characteristics and program attrition
rates compared to others initiating and already receiving ART. 156,474 HIV
infected individuals (67.0% women) started ART. The proportion of individuals
starting ART who were pregnant women rose from 5.3% in 2004 to 12.2% in 2014.
Mean CD4 cell counts at ART initiation, weighted for annual program size,
increased from 2004 to 2014, led by non-pregnant women (annual increase 20
cells/mm3) and men (17 cells/mm3 annually), with lower rates of change in
pregnant women (10 cells/mm3 per year) (p<0.0001). There was no significant
difference in the cumulative incidence of program attrition at 6 months among
pregnant women starting ART and non-pregnant women. However, healthy pregnant
women starting ART (WHO stage 1/2) had a higher rate of attrition rate (9.6%),
compared with healthy non-pregnant women (6.5%); in contrast among women with WHO
stage 3/4 disease, pregnant women had lower attrition (8.4%) than non-pregnant
women (14.4%). Among women who initiated ART when healthy and remained in care
for six months, subsequent six-month attrition was slightly higher among pregnant
women at ART start (3.5%) compared to those who were not pregnant (2.4%),
(absolute difference 1.1%, 95% CI 0.7%-1.5%). CONCLUSIONS: Pregnant women
comprise an increasing proportion of those initiating ART in Africa, and pregnant
women starting ART while healthy are at higher risk for program attrition than
non-pregnant women. As ART programs further expand access to healthier pregnant
women, further studies are needed to better understand the drivers of loss among
this high risk group of women to optimize retention.
PMID- 29342181
TI - Optimization of mNeonGreen for Homo sapiens increases its fluorescent intensity
in mammalian cells.
AB - Green fluorescent protein (GFP) is tremendously useful for investigating many
cellular and intracellular events. The monomeric GFP mNeonGreen is about 3- to 5
times brighter than GFP and monomeric enhanced GFP and shows high photostability.
The maturation half-time of mNeonGreen is about 3-fold faster than that of
monomeric enhanced GFP. However, the cDNA sequence encoding mNeonGreen contains
some codons that are rarely used in Homo sapiens. For better expression of
mNeonGreen in human cells, we synthesized a human-optimized cDNA encoding
mNeonGreen and generated an expression plasmid for humanized mNeonGreen under the
control of the cytomegalovirus promoter. The resultant plasmid was introduced
into HEK293 cells. The fluorescent intensity of humanized mNeonGreen was about
1.4-fold higher than that of the original mNeonGreen. The humanized mNeonGreen
with a mitochondria-targeting signal showed mitochondrial distribution of
mNeonGreen. We further generated an expression vector of humanized mNeonGreen
with 3xFLAG tags at its carboxyl terminus as these tags are useful for
immunological analyses. The 3xFLAG-tagged mNeonGreen was recognized well with an
anti-FLAG-M2 antibody. These plasmids for the expression of humanized mNeonGreen
and mNeonGreen-3xFLAG are useful tools for biological studies in mammalian cells
using mNeonGreen.
PMID- 29342182
TI - Light alcohol consumption has the potential to suppress hepatocellular injury and
liver fibrosis in non-alcoholic fatty liver disease.
AB - BACKGROUND & AIMS: The modest consumption of alcohol has been reported to
decrease the incidence of fatty liver or prevalence of steatohepatitis. In this
study, we investigated the effect of light alcohol consumption on liver function
and gene expression in patients with non-alcoholic fatty liver disease (NAFLD).
METHODS: The study group was formed of 178 patients diagnosed with non-alcoholic
fatty liver disease, subclassified into two groups for analysis based on the
daily alcohol consumption: non-alcohol group and light alcohol consumer group
(<=20 g of ethanol/day). Clinical characteristics, liver histological features,
gene expression, comprehensively analyzed using microarrays (BRB-Array tools),
and molecular network were evaluated and compared between the two groups.
RESULTS: No significant differences in steatosis or inflammation score were noted
among the groups. However, the ballooning and fibrosis scores were significantly
lower in the light alcohol consumer group than in the non-alcohol group. Gene
expression analysis revealed a marked inhibition of the pathways involved in the
immune response in the light alcohol group compared to that in the non-alcohol
group. CONCLUSIONS: Light alcohol consumption might suppress activity of non
alcoholic steatohepatitis by reducing gene expression levels involved in the
immune response. This inhibition in gene expression was associated with a
lowering of liver fibrosis and hepatocellular injury.
PMID- 29342183
TI - Identification of volatiles released by diapausing brown marmorated stink bug,
Halyomorpha halys (Hemiptera: Pentatomidae).
AB - The brown marmorated stink bug, Halyomorpha halys, is an agricultural and urban
pest that has become widely established as an invasive species of major concern
in the USA and across Europe. This species forms large aggregations when entering
diapause, and it is often these aggregations that are found by officials
conducting inspections of internationally shipped freight. Identifying the
presence of diapausing aggregations of H. halys using their emissions of volatile
organic compounds (VOCs) may be a potential means for detecting and intercepting
them during international freight inspections. Headspace samples were collected
from aggregations of diapausing H. halys using volatile collection traps (VCTs)
and solid phase microextraction. The only compound detected in all samples was
tridecane, with small amounts of (E)-2-decenal found in most samples. We also
monitored the release of defensive odors, following mechanical agitation of
diapausing and diapause-disrupted adult H. halys. Diapausing groups were
significantly more likely to release defensive odors than diapause-disrupted
groups. The predominant compounds consistently found from both groups were
tridecane, (E)-2-decenal, and 4-oxo-(E)-2-hexenal, with a small abundance of
dodecane. Our findings show that diapausing H. halys do release defensive
compounds, and suggest that volatile sampling may be feasible to detect H. halys
in freight.
PMID- 29342184
TI - Species delimitation in the Stenocereus griseus (Cactaceae) species complex
reveals a new species, S. huastecorum.
AB - The Stenocereus griseus species complex (SGSC) has long been considered
taxonomically challenging because the number of taxa belonging to the complex and
their geographical boundaries remain poorly understood. Bayesian clustering and
genetic distance-based methods were used based on nine microsatellite loci in 377
individuals of three main putative species of the complex. The resulting genetic
clusters were assessed for ecological niche divergence and areolar morphology,
particularly spination patterns. We based our species boundaries on concordance
between genetic, ecological, and morphological data, and were able to resolve
four species, three of them corresponding to S. pruinosus from central Mexico, S.
laevigatus from southern Mexico, and S. griseus from northern South America. A
fourth species, previously considered to be S. griseus and commonly misidentified
as S. pruinosus in northern Mexico showed significant genetic, ecological, and
morphological differentiation suggesting that it should be considered a new
species, S. huastecorum, which we describe here. We show that population genetic
analyses, ecological niche modeling, and morphological studies are complementary
approaches for delimiting species in taxonomically challenging plant groups such
as the SGSC.
PMID- 29342185
TI - Nanocarrier-mediated foliar zinc fertilization influences expression of metal
homeostasis related genes in flag leaves and enhances gluten content in durum
wheat.
AB - BACKGROUND: Wheat is the staple food for most of the world's population; however,
it is a poor source of zinc. Foliar fertilization of zinc via zinc loaded
chitosan nanocarriers (Zn-CNP) post-anthesis has proved to be a promising
approach for grain zinc enhancement in durum wheat as evidenced in our earlier
study. However, the molecular mechanism of uptake of zinc via Zn-CNP remains
unclear. METHODS/PRINCIPLE FINDINGS: Foliar application of Zn-CNP was performed
at post anthesis stages in two durum wheat cultivars (MACS 3125 and UC1114,
containing the Gpc-B1 gene), and expression levels of several metal-related genes
were analyzed during early senescence. Zn-CNP application indeed caused changes
in gene expression as revealed by qPCR data on representative genes involved in
metal homeostasis, phloem transporters, and leaf senescence. Furthermore, zinc
regulated transporters and iron (Fe)-regulated transporter-like protein (ZIP)
family [ZIP1, ZIP7, ZIP15], CA (carbonic anhydrase), and DMAS (2'-deoxymugineic
acid synthase) in flag leaves exhibited significant correlation with zinc content
in the seeds. The analysis of grain endosperm proteins showed enhancement of
gamma gliadins while other gluten subunits decreased. Gene expression within ZIP
family members varied with the type of cultivar mostly attributed to the Gpc-B1,
concentration of external zinc ions as well as the type of tissue analyzed.
Correlation analysis revealed the involvement of the selected genes in zinc
enhancement. CONCLUSION: At the molecular level, uptake of zinc via Zn-CNP
nanocarrier was comparable to the uptake of zinc via common zinc fertilizers i.e.
ZnSO4.
PMID- 29342186
TI - Doxorubicin-provoked increase of mitotic activity and concomitant drain of G0
pool in therapy-resistant BE(2)-C neuroblastoma.
AB - In this study chemotherapy response in neuroblastoma (NB) was assessed for the
first time in a transplantation model comprising non-malignant human embryonic
microenvironment of pluripotent stem cell teratoma (PSCT) derived from diploid
bona fide hESC. Two NB cell lines with known high-risk phenotypes; the multi
resistant BE(2)-C and the drug sensitive IMR-32, were transplanted to the PSCT
model and the tumour growth was exposed to single or repeated treatments with
doxorubicin, and thereafter evaluated for cell death, apoptosis, and
proliferation. Dose dependent cytotoxic effects were observed, this way
corroborating the experimental platform for this type of analysis. Notably,
analysis of doxorubicin-resilient BE(2)-C growth in the PSCT model revealed an
unexpected 1,5-fold increase in Ki67-index (p<0.05), indicating that non-cycling
(G0) cells entered the cell cycle following the doxorubicin exposure. Support for
this notion was obtained also in vitro. A pharmacologically relevant dose (1MUM)
resulted in a marked accumulation of Ki67 positive BE(2)-C cells (p<0.0001), as
well as a >3-fold increase in active cell cycle (i.e. cells positive staining for
PH3 together with incorporation of EdU) (p<0.01). Considering the clinical
challenge for treating high-risk NB, the discovery of a therapy-provoked growth
stimulating effect in the multi-resistant and p53-mutated BE(2)-C cell line, but
not in the drug-sensitive p53wt IMR-32 cell line, warrants further studies
concerning generality and clinical significance of this new observation.
PMID- 29342187
TI - Induction of high tolerance to artemisinin by sub-lethal administration: A new in
vitro model of P. falciparum.
AB - Artemisinin resistance is a major threat to malaria control efforts. Resistance
is characterized by an increase in the Plasmodium falciparum parasite clearance
half-life following treatment with artemisinin-based combination therapies (ACTs)
and an increase in the percentage of surviving parasites. The remarkably short
blood half-life of artemisinin derivatives may contribute to drug-resistance,
possibly through factors including sub-lethal plasma concentrations and
inadequate exposure. Here we selected for a new strain of artemisinin resistant
parasites, termed the artemisinin resistant strain 1 (ARS1), by treating P.
falciparum Palo Alto (PA) cultures with sub-lethal concentrations of
dihydroartemisinin (DHA). The resistance phenotype was maintained for over 1 year
through monthly maintenance treatments with low doses of 2.5 nM DHA. There was a
moderate increase in the DHA IC50 in ARS1 when compared with parental strain PA
after 72 h of drug exposure (from 0.68 nM to 2 nM DHA). In addition, ARS1
survived treatment physiologically relevant DHA concentrations (700 nM) observed
in patients. Furthermore, we confirmed a lack of cross-resistance against a panel
of antimalarials commonly used as partner drugs in ACTs. Finally, ARS1 did not
contain Pfk13 propeller domain mutations associated with ART resistance in the
Greater Mekong Region. With a stable growth rate, ARS1 represents a valuable tool
for the development of new antimalarial compounds and studies to further
elucidate the mechanisms of ART resistance.
PMID- 29342188
TI - Comparative analysis of gene expression identifies distinct molecular signatures
of bone marrow- and periosteal-skeletal stem/progenitor cells.
AB - Periosteum and bone marrow (BM) both contain skeletal stem/progenitor cells
(SSCs) that participate in fracture repair. However, the functional difference
and selective regulatory mechanisms of SSCs in different locations are unknown
due to the lack of specific markers. Here, we report a comprehensive gene
expression analysis of bone marrow SSCs (BM-SSCs), periosteal SSCs (P-SSCs), and
more differentiated osteoprogenitors by using reporter mice expressing Interferon
inducible Mx1 and NestinGFP, previously known SSC markers. We first defined that
the BM-SSCs can be enriched by the combination of Mx1 and NestinGFP expression,
while endogenous P-SSCs can be isolated by positive selection of Mx1, CD105 and
CD140a (known SSC markers) combined with the negative selection of CD45, CD31,
and osteocalcinGFP (a mature osteoblast marker). Comparative gene expression
analysis with FACS-sorted BM-SSCs, P-SSCs, Osterix+ preosteoblasts, CD51+ stroma
cells and CD45+ hematopoietic cells as controls revealed that BM-SSCs and P-SSCs
have high similarity with few potential differences without statistical
significance. We also found that CD51+ cells are highly heterogeneous and have
little overlap with SSCs. This was further supported by the microarray cluster
analysis, where the two SSC populations clustered together but are separate from
the CD51+ cells. However, when comparing SSC population to controls, we found
several genes that are uniquely upregulated in endogenous SSCs. Amongst these
genes, we found KDR (aka Flk1 or VEGFR2) to be most interesting and discovered
that it is highly and selectively expressed in P-SSCs. This finding suggests that
endogenous P-SSCs are functionally very similar to BM-SSCs with undetectable
significant differences in gene expression but there are distinct molecular
signatures in P-SSCs, which can be useful to specify P-SSC subset in vivo.
PMID- 29342190
TI - Potential of vegetation indices combined with laser-induced fluorescence
parameters for monitoring leaf nitrogen content in paddy rice.
AB - Nitrogen (N) is important for the growth of crops. Leaf nitrogen content (LNC)
serves as a crucial indicator of the growth status of crops and can help
determine the dose of N fertilizer. Laser-induced fluorescence (LIF) technology
and the reflectance spectra of crops are widely used to detect the biochemical
content of leaves. Many vegetation indices (VIs) and fluorescence parameters have
been developed to estimate LNC. However, the comparison among VIs and between
fluorescence parameters and VIs has been rarely studied in the estimation of LNC.
In this study, the performances of several published empirical VIs and
fluorescence parameters for the estimation of paddy rice LNC were analyzed using
the support vector machine (SVM) algorithm. Then, the optimal VIs (TVI, MTVI1,
MTVI2, and MSAVI) and fluorescence parameters (F735/F460 and F685/F460), which
were suitable for LNC monitoring in this study, were chosen. In addition, the
combination of the VIs and fluorescence parameters was proposed as the input
variables in the SVM model and used to estimate the LNC. Experimental results
exhibited the promising potential of the LIF technology combined with reflectance
for the accurate estimation of LNC, which provided guidance for monitoring the
LNC.
PMID- 29342189
TI - The microbiota metabolite indole inhibits Salmonella virulence: Involvement of
the PhoPQ two-component system.
AB - The microbial community present in the gastrointestinal tract is an important
component of the host defense against pathogen infections. We previously
demonstrated that indole, a microbial metabolite of tryptophan, reduces
enterohemorrhagic Escherichia coli O157:H7 attachment to intestinal epithelial
cells and biofilm formation, suggesting that indole may be an effector/attenuator
of colonization for a number of enteric pathogens. Here, we report that indole
attenuates Salmonella Typhimurium (Salmonella) virulence and invasion as well as
increases resistance to colonization in host cells. Indole-exposed Salmonella
colonized mice less effectively compared to solvent-treated controls, as evident
by competitive index values less than 1 in multiple organs. Indole-exposed
Salmonella demonstrated 160-fold less invasion of HeLa epithelial cells and 2
fold less invasion of J774A.1 macrophages compared to solvent-treated controls.
However, indole did not affect Salmonella intracellular survival in J774A.1
macrophages suggesting that indole primarily affects Salmonella invasion. The
decrease in invasion was corroborated by a decrease in expression of multiple
Salmonella Pathogenicity Island-1 (SPI-1) genes. We also identified that the
effect of indole was mediated by both PhoPQ-dependent and independent mechanisms.
Indole also synergistically enhanced the inhibitory effect of a short chain fatty
acid cocktail on SPI-1 gene expression. Lastly, indole-treated HeLa cells were
70% more resistant to Salmonella invasion suggesting that indole also increases
resistance of epithelial cells to colonization. Our results demonstrate that
indole is an important microbiota metabolite that has direct anti-infective
effects on Salmonella and host cells, revealing novel mechanisms of pathogen
colonization resistance.
PMID- 29342191
TI - Changes in balance and joint position sense during a 12-day high altitude trek:
The British Services Dhaulagiri medical research expedition.
AB - Postural control and joint position sense are essential for safely undertaking
leisure and professional activities, particularly at high altitude. We tested
whether exposure to a 12-day trek with a gradual ascent to high altitude impairs
postural control and joint position sense. This was a repeated measures
observational study of 12 military service personnel (28+/-4 years). Postural
control (sway velocity measured by a portable force platform) during standing
balance, a Sharpened Romberg Test and knee joint position sense were measured, in
England (113m elevation) and at 3 research camps (3619m, 4600m and 5140m) on a 12
day high altitude trek in the Dhaulagiri region of Nepal. Pulse oximetry, and
Lake Louise scores were also recorded on the morning and evening of each trek
day. Data were compared between altitudes and relationships between pulse
oximetry, Lake Louise score, and sway velocity were explored. Total sway velocity
during standing balance with eyes open (p = 0.003, d = 1.9) and during Sharpened
Romberg test with eyes open (p = 0.007, d = 1.6) was significantly greater at
altitudes of 3619m and 5140m when compared with sea level. Anterior-posterior
sway velocity during standing balance with eyes open was also significantly
greater at altitudes of 3619m and 5140m when compared with sea level (p = 0.001,
d = 1.9). Knee joint position sense was not altered at higher altitudes. There
were no significant correlations between Lake Louise scores, pulse oximetry and
postural sway. Despite a gradual ascent profile, exposure to 3619 m was
associated with impairments in postural control without impairment in knee joint
position sense. Importantly, these impairments did not worsen at higher altitudes
of 4600 m or 5140 m. The present findings should be considered during future
trekking expeditions when developing training strategies targeted to manage
impairments in postural control that occur with increasing altitude.
PMID- 29342192
TI - White matter tract-specific quantitative analysis in multiple sclerosis:
Comparison of optic radiation reconstruction techniques.
AB - The posterior visual pathway is commonly affected by multiple sclerosis (MS)
pathology that results in measurable clinical and electrophysiological
impairment. Due to its highly structured retinotopic mapping, the visual pathway
represents an ideal substrate for investigating patho-mechanisms in MS.
Therefore, a reliable and robust imaging segmentation method for in-vivo
delineation of the optic radiations (OR) is needed. However, diffusion-based
tractography approaches, which are typically used for OR segmentation are
confounded by the presence of focal white matter lesions. Current solutions
require complex acquisition paradigms and demand expert image analysis, limiting
application in both clinical trials and clinical practice. In the current study,
using data acquired in a clinical setting on a 3T scanner, we optimised and
compared two approaches for optic radiation (OR) reconstruction: individual
probabilistic tractography-based and template-based methods. OR segmentation
results were applied to subjects with MS and volumetric and diffusivity
parameters were compared between OR segmentation techniques. Despite differences
in reconstructed OR volumes, both OR lesion volume and OR diffusivity
measurements in MS subjects were highly comparable using optimised probabilistic
tractography-based, and template-based, methods. The choice of OR reconstruction
technique should be determined primarily by the research question and the nature
of the available dataset. Template-based approaches are particularly suited to
the semi-automated analysis of large image datasets and have utility even in the
absence of dMRI acquisitions. Individual tractography methods, while more complex
than template based OR reconstruction, permit measurement of diffusivity changes
along fibre bundles that are affected by specific MS lesions or other focal
pathologies.
PMID- 29342193
TI - Analysis of copy number loss of the ErbB4 receptor tyrosine kinase in
glioblastoma.
AB - Current treatments for glioblastoma multiforme (GBM)-an aggressive form of brain
cancer-are minimally effective and yield a median survival of 14.6 months and a
two-year survival rate of 30%. Given the severity of GBM and the limitations of
its treatment, there is a need for the discovery of novel drug targets for GBM
and more personalized treatment approaches based on the characteristics of an
individual's tumor. Most receptor tyrosine kinases-such as EGFR-act as oncogenes,
but publicly available data from the Cancer Cell Line Encyclopedia (CCLE)
indicates copy number loss in the ERBB4 RTK gene across dozens of GBM cell lines,
suggesting a potential tumor suppressor role. This loss is mutually exclusive
with loss of its cognate ligand NRG1 in CCLE as well, more strongly suggesting a
functional role. The availability of higher resolution copy number data from
clinical GBM patients in The Cancer Genome Atlas (TCGA) revealed that a region in
Intron 1 of the ERBB4 gene was deleted in 69.1% of tumor samples harboring ERBB4
copy number loss; however, it was also found to be deleted in the matched normal
tissue samples from these GBM patients (n = 81). Using the DECIPHER Genome
Browser, we also discovered that this mutation occurs at approximately the same
frequency in the general population as it does in the disease population. We
conclude from these results that this loss in Intron 1 of the ERBB4 gene is
neither a de novo driver mutation nor a predisposing factor to GBM, despite the
indications from CCLE. A biological role of this significantly occurring genetic
alteration is still unknown. While this is a negative result, the broader
conclusion is that while copy number data from large cell line-based data
repositories may yield compelling hypotheses, careful follow up with higher
resolution copy number assays, patient data, and general population analyses are
essential to codify initial hypotheses prior to investing experimental resources.
PMID- 29342194
TI - Tolerance to mild salinity stress in japonica rice: A genome-wide association
mapping study highlights calcium signaling and metabolism genes.
AB - Salinity tolerance is an important quality for European rice grown in river
deltas. We evaluated the salinity tolerance of a panel of 235 temperate japonica
rice accessions genotyped with 30,000 SNP markers. The panel was exposed to mild
salt stress (50 mM NaCl; conductivity of 6 dS m-1) at the seedling stage. Eight
different root and shoot growth parameters were measured for both the control and
stressed treatments. The Na+ and K+ mass fractions of the stressed plants were
measured using atomic absorption spectroscopy. The salt treatment affected plant
growth, particularly the shoot parameters. The panel showed a wide range of
Na+/K+ ratio and the temperate accessions were distributed over an increasing
axis, from the most resistant to the most susceptible checks. We conducted a
genome-wide association study on indices of stress response and ion mass
fractions in the leaves using a classical mixed model controlling structure and
kinship. A total of 27 QTLs validated by sub-sampling were identified. For
indices of stress responses, we also used another model that focused on marker *
treatment interactions and detected 50 QTLs, three of which were also identified
using the classical method. We compared the positions of the significant QTLs to
those of approximately 300 genes that play a role in rice salt tolerance. The
positions of several QTLs were close to those of genes involved in calcium
signaling and metabolism, while other QTLs were close to those of kinases. These
results reveal the salinity tolerance of accessions with a temperate japonica
background. Although the detected QTLs must be confirmed by other approaches, the
number of associations linked to candidate genes involved in calcium-mediated ion
homeostasis highlights pathways to explore in priority to understand the salinity
tolerance of temperate rice.
PMID- 29342195
TI - Association between PM10, PM2.5, NO2, O3 and self-reported diabetes in Italy: A
cross-sectional, ecological study.
AB - INTRODUCTION: Air pollution represents a serious threat to health on a global
scale, being responsible for a large portion of the global burden of disease from
environmental factors. Current evidence about the association between air
pollution exposure and Diabetes Mellitus (DM) is still controversial. We aimed to
evaluate the association between area-level ambient air pollution and self
reported DM in a large population sample in Italy. MATERIALS AND METHODS: We
extracted information about self-reported and physician diagnosed DM, risk
factors and socio-economic status from 12 surveys conducted nationwide between
1999 and 2013. We obtained annual averaged air pollution levels for the years
2003, 2005, 2007 and 2010 from the AMS-MINNI national integrated model, which
simulates the dispersion and transformation of pollutants. The original maps,
with a resolution of 4 x 4 km2, were normalized and aggregated at the
municipality class of each Italian region, in order to match the survey data. We
fit logistic regression models with a hierarchical structure to estimate the
relationship between PM10, PM2.5, NO2 and O3 four-years mean levels and the risk
of being affected by DM. RESULTS: We included 376,157 individuals aged more than
45 years. There were 39,969 cases of DM, with an average regional prevalence of
9.8% and a positive geographical North-to-South gradient, opposite to that of
pollutants' concentrations. For each 10 MUg/m3 increase, the resulting ORs were
1.04 (95% CI 1.01-1.07) for PM10, 1.04 (95% CI 1.02-1.07) for PM2.5, 1.03 (95% CI
1.01-1.05) for NO2 and 1.06 (95% CI 1.01-1.11) for O3, after accounting for
relevant individual risk factors. The associations were robust to adjustment for
other pollutants in two-pollutant models tested (ozone plus each other
pollutant). CONCLUSIONS: We observed a significant positive association between
each examined pollutant and prevalent DM. Risk estimates were consistent with
current evidence, and robust to sensitivity analysis. Our study adds evidence
about the effects of air pollution on diabetes and suggests a possible role of
ozone as an independent factor associated with the development of DM. Such
relationship is of great interest for public health and deserves further
investigation.
PMID- 29342196
TI - Low fitness is associated with abdominal adiposity and low-grade inflammation
independent of BMI.
AB - OBJECTIVE: Up to 30% of obese individuals are metabolically healthy.
Metabolically healthy obese (MHO) individuals are characterized by having low
abdominal adiposity, low inflammation level and low risk of developing metabolic
comorbidity. In this study, we hypothesize that cardiorespiratory fitness
(fitness) is a determinant factor for the MHO individuals and aim to investigate
the associations between fitness, abdominal adiposity and low-grade inflammation
within different BMI categories. METHOD: Data from 10,976 individuals from the
general population, DANHES 2007-2008, on waist circumference, fitness and C
reactive protein (hsCRP) were analysed using multiple linear and median quantile
regressions. RESULTS: In men, an inverse association between fitness (+5 mL min-1
kg-1) and waist circumference (-1.45 cm; 95% CI: -1.55 to -1.35 cm; p<0.001), and
an inverse association between fitness (+5 mL min-1 kg-1) and hsCRP (-0.22 mg/L;
95% CI: -0.255 to -0.185 mg/L; p<0.001) was found, all independent of BMI.
Similarly in women, an inverse association between fitness (+5 mL min-1 kg-1) and
waist circumference (-1.15 cm; 95% CI: -1.25 to -1.0 cm; p<0.001), and an inverse
association between fitness (+5 mL min-1 kg-1) and hsCRP (-0.26 mg/L; 95% CI:
0.3 to -0.22 mg/L; p<0.001) was found, all independent of BMI. Additionally,
significant positive associations between waist circumference and hsCRP were
found for both men and women, independently of BMI. CONCLUSION: Fitness was found
to be inversely associated with both abdominal adiposity and low-grade
inflammation independent of BMI. These data suggest that, in spite of BMI, high
fitness levels lead to a reduction in abdominal fat mass and low-grade
inflammation.
PMID- 29342197
TI - Molecular discrimination of tall fescue morphotypes in association with Festuca
relatives.
AB - Tall fescue (Festuca arundinacea Schreb.) is an important cool-season perennial
grass species used as forage and turf, and in conservation plantings. There are
three morphotypes in hexaploid tall fescue: Continental, Mediterranean and
Rhizomatous. This study was conducted to develop morphotype-specific molecular
markers to distinguish Continental and Mediterranean tall fescues, and establish
their relationships with other species of the Festuca genus for genomic
inference. Chloroplast sequence variation and simple sequence repeat (SSR)
polymorphism were explored in 12 genotypes of three tall fescue morphotypes and
four Festuca species. Hypervariable chloroplast regions were retrieved by using
33 specifically designed primers followed by sequencing the PCR products. SSR
polymorphism was studied using 144 tall fescue SSR primers. Four chloroplast
(NFTCHL17, NFTCHL43, NFTCHL45 and NFTCHL48) and three SSR (nffa090, nffa204 and
nffa338) markers were identified which can distinctly differentiate Continental
and Mediterranean morphotypes. A primer pair, NFTCHL45, amplified a 47 bp
deletion between the two morphotypes is being routinely used in the Noble
Research Institute's core facility for morphotype discrimination. Both
chloroplast sequence variation and SSR diversity showed a close association
between Rhizomatous and Continental morphotypes, while the Mediterranean
morphotype was in a distant clade. F. pratensis and F. arundinacea var.
glaucescens, the P and G1G2 genome donors, respectively, were grouped with the
Continental clade, and F. mairei (M1M2 genome) grouped with the Mediterranean
clade in chloroplast sequence variation, while both F. pratensis and F. mairei
formed independent clade in SSR analysis. Age estimation based on chloroplast
sequence variation indicated that the Continental and Mediterranean clades might
have been colonized independently during 0.65 +/- 0.06 and 0.96 +/- 0.1 million
years ago (Mya) respectively. The findings of the study will enhance tall fescue
breeding for persistence and productivity.
PMID- 29342198
TI - Three-dimensional printing model improves morphological understanding in
acetabular fracture learning: A multicenter, randomized, controlled study.
AB - Conventional education results in unsatisfactory morphological understanding of
acetabular fractures due to lack of three-dimensional (3D) details and tactile
feedback of real fractures. Virtual reality (VR) and 3D printing (3DP) techniques
are widely applied in teaching. The purpose of this study was to identify the
effect of physical model (PM), VR and 3DP models in education of morphological
understanding of acetabular fractures. 141 students were invited to participate
in this study. Participants were equally and randomly assigned to the PM, VR and
3DP learning groups. Three-level objective tests were conducted to evaluate
learning, including identifying anatomical landmarks, describing fracture lines,
identifying classification, and inferring fracture mechanism. Four subjective
questions were asked to evaluate the usability and value of instructional
materials. Generally, the 3DP group showed a clear advantage over the PM and VR
groups in objective tests, while there was no significant difference between the
PM and VR groups. 3DP was considered to be the most valuable learning tool for
understanding acetabular fractures. The findings demonstrate that 3DP modelling
of real fractures is an effective learning instrument that can be used to
understand the morphology of acetabular fractures and promote subjective
interest.
PMID- 29342199
TI - A non-linear pharmacokinetic-pharmacodynamic relationship of metformin in healthy
volunteers: An open-label, parallel group, randomized clinical study.
AB - BACKGROUND: The aim of this study was to explore the pharmacokinetic
pharmacodynamic (PK-PD) relationship of metformin on glucose levels after the
administration of 250 mg and 1000 mg of metformin in healthy volunteers. METHODS:
A total of 20 healthy male volunteers were randomized to receive two doses of
either a low dose (375 mg followed by 250 mg) or a high dose (1000 mg followed by
1000 mg) of metformin at 12-h intervals. The pharmacodynamics of metformin was
assessed using oral glucose tolerance tests before and after metformin
administration. The PK parameters after the second dose were evaluated through
noncompartmental analyses. Four single nucleotide polymorphisms in MATE1, MATE2
K, and OCT2 were genotyped, and their effects on PK characteristics were
additionally evaluated. RESULTS: The plasma exposure of metformin increased as
the metformin dose increased. The mean values for the area under the
concentration-time curve from dosing to 12 hours post-dose (AUC0-12h) were 3160.4
and 8808.2 h.MUg/L for the low- and high-dose groups, respectively. Non-linear
relationships were found between the glucose-lowering effect and PK parameters
with a significant inverse trend at high metformin exposure. The PK parameters
were comparable among subjects with the genetic polymorphisms. CONCLUSIONS: This
study showed a non-linear PK-PD relationship on plasma glucose levels after the
administration of metformin. The inverse relationship between systemic exposure
and the glucose-lowering effect at a high exposure indicates a possible role for
the intestines as an action site for metformin. TRIAL REGISTRATION:
ClinicalTrials.gov NCT02712619.
PMID- 29342200
TI - Inhibiting TGF-beta signaling preserves the function of highly activated, in
vitro expanded natural killer cells in AML and colon cancer models.
AB - Natural killer cells harnessed from healthy individuals can be expanded ex vivo
using various platforms to produce large doses for adoptive transfer into cancer
patients. During such expansion, NK cells are increasingly activated and more
efficient at killing cancer cells. Adoptive transfer however introduces these
activated cells into a highly immunosuppressive tumor microenvironment mediated
in part by excessive transforming growth factor beta (TGF-beta) from both cancer
cells and their surrounding stroma. This microenvironment ultimately limits the
clinical efficacy of NK cell therapy. In this study, we examined the use of a TGF
beta receptor kinase inhibitor, LY2157299, in preserving the cytotoxic function
of ex vivo expanded, highly activated NK cells following sustained exposure to
pathologic levels of TGF-beta in vitro and in a liver metastases model of colon
cancer. Using myeloid leukemia and colon cancer cell lines, we show that the TGF
beta driven impairment of NK cell cytotoxicity is mitigated by LY2157299. We
demonstrate this effect using quantitative cytotoxicity assays as well as by
showing a preserved activated phenotype with high NKG2D/CD16 expression and
enhanced cytokine production. In a mouse liver metastases model of colon cancer,
we observed significantly improved eradication of liver metastases in mice
treated with adoptive NK cells combined with LY2157299 compared with mice
receiving NK cells or TGF beta inhibition alone. We propose that the therapeutic
efficacy of adoptive NK cell therapy clinically will be markedly enhanced by
complementary approaches targeting TGF-beta signaling in vivo.
PMID- 29342201
TI - Differentiation of glioblastoma multiforme, metastases and primary central
nervous system lymphomas using multiparametric perfusion and diffusion MR imaging
of a tumor core and a peritumoral zone-Searching for a practical approach.
AB - INTRODUCTION: In conventional MR examinations glioblastomas multiforme (GBMs),
metastases and primary CNS lymphomas (PCNSLs) may show very similar appearance.
The aim of the study was to evaluate usefulness of multiparametric T2*DSC
perfusion and diffusion MR imaging in the preoperative differentiation of these
tumors. MATERIAL AND METHODS: Seventy four solitary enhancing tumors (27 GBMs, 30
metastases, 17 PCNSLs) were enrolled in the study. Parameters of cerebral blood
volume (rCBV), peak height (rPH), percentage of signal recovery (rPSR) and
apparent diffusion coefficient (ADC) were assessed from the tumor core and the
peritumoral non-enhancing T2-hyperintense zone. RESULTS: Within the tumor core
there were no differences in perfusion and diffusion parameters between GBMs and
metastases. Compared to GBMs and metastases, PCNSLs showed significantly lower
rCBV and rPH, ADC as well as higher rPSR values. Max rCBV with a cut-off value of
2.18 demonstrated the highest accuracy of 0.98 in differentiating PCNSLs from
other tumors. To distinguish GBMs from metastases analysis of the peritumoral
zone was performed showing significantly higher rCBV, rPH and lower ADC values in
GBMs with the highest accuracy of 0.94 found for max rCBV at a cut-off value of
0.98. CONCLUSIONS: Max rCBV seems to be the most important parameter to
differentiate GBMs, metastases and PCNSLs. Analysis of max rCBV within the tumor
core enables to distinguish hypoperfused PCNSLs from hyperperfused GBMs and
metastases while evaluation of max rCBV within the peritumoral zone is helpful to
distinguish GBMs showing peritumoral infiltration from metastases surrounded by
pure edema.
PMID- 29342202
TI - Cells containing aragonite crystals mediate responses to gravity in Trichoplax
adhaerens (Placozoa), an animal lacking neurons and synapses.
AB - Trichoplax adhaerens has only six cell types. The function as well as the
structure of crystal cells, the least numerous cell type, presented an enigma.
Crystal cells are arrayed around the perimeter of the animal and each contains a
birefringent crystal. Crystal cells resemble lithocytes in other animals so we
looked for evidence they are gravity sensors. Confocal microscopy showed that
their cup-shaped nuclei are oriented toward the edge of the animal, and that the
crystal shifts downward under the influence of gravity. Some animals
spontaneously lack crystal cells and these animals behaved differently upon being
tilted vertically than animals with a typical number of crystal cells. EM
revealed crystal cell contacts with fiber cells and epithelial cells but these
contacts lacked features of synapses. EM spectroscopic analyses showed that
crystals consist of the aragonite form of calcium carbonate. We thus provide
behavioral evidence that Trichoplax are able to sense gravity, and that crystal
cells are likely to be their gravity receptors. Moreover, because placozoans are
thought to have evolved during Ediacaran or Cryogenian eras associated with
aragonite seas, and their crystals are made of aragonite, they may have acquired
gravity sensors during this early era.
PMID- 29342203
TI - Biological pathways underlying the association of red cell distribution width and
adverse clinical outcome: Results of a prospective cohort study.
AB - BACKGROUND: Red cell distribution width (RDW) predicts disease outcome in several
patient populations, but its prognostic value in addition to other disease
parameters in unselected medical inpatients remains unclear. Our aim was to
investigate the association of admission RDW levels and mortality adjusted for
several disease pathways in unselected medical patients from a previous
multicenter study. METHODS: We included consecutive adult, medical patients at
the time point of hospital admission through the emergency department into this
observational, cohort study. The primary endpoint was mortality at 30-day. To
study association of admission RDW and outcomes, we calculated regression
analysis with step-wise inclusion of clinical and laboratory parameters from
different biological pathways. RESULTS: The 30-day mortality of the 4273 included
patients was 5.6% and increased from 1.4% to 14.3% from the lowest to the highest
RDW quartile. There was a strong association of RDW and mortality in unadjusted
analysis (OR 1.32; 95%CI 1.27-1.39, p<0.001). RDW was strongly correlated with
different pathways including inflammation (coefficient of determination (R2)
0.30; p<0.001), nutrition (R2 0.20; p<0.001) and blood diseases (R2 0.30; p<0.001
The association was eliminated after including different biological pathways into
the models with the fully adjusted regression model showing an OR of 1.02 (95%CI
0.93-1.12; p = 0.664) for the association of RDW and mortality. Similar effects
were found for other outcomes including intensive care unit admission and
hospital readmission. CONCLUSION: Our data suggests that RDW is a strong
surrogate marker of mortality in unselected medical inpatients with most of the
prognostic information being explained by other disease factors. The strong
correlation of RDW and different biological pathways such as chronic
inflammation, malnutrition and blood disease suggest that RDW may be viewed as an
unspecific and general "chronic disease prognostic marker".
PMID- 29342204
TI - Bulk metal concentrations versus total suspended solids in rivers: Time-invariant
& catchment-specific relationships.
AB - Suspended particles in rivers can act as carriers of potentially bioavailable
metal species and are thus an emerging area of interest in river system
monitoring. The delineation of bulk metals concentrations in river water into
dissolved and particulate components is also important for risk assessment.
Linear relationships between bulk metal concentrations in water (CW,tot) and
total suspended solids (TSS) in water can be used to easily evaluate dissolved
(CW, intercept) and particle-bound metal fluxes (CSUS, slope) in streams (CW,tot
= CW + CSUS TSS). In this study, we apply this principle to catchments in Iran
(Haraz) and Germany (Ammer, Goldersbach, and Steinlach) that show differences in
geology, geochemistry, land use and hydrological characteristics. For each
catchment, particle-bound and dissolved concentrations for a suite of metals in
water were calculated based on linear regressions of total suspended solids and
total metal concentrations. Results were replicable across sampling campaigns in
different years and seasons (between 2013 and 2016) and could be reproduced in a
laboratory sedimentation experiment. CSUS values generally showed little
variability in different catchments and agree well with soil background values
for some metals (e.g. lead and nickel) while other metals (e.g. copper) indicate
anthropogenic influences. CW was elevated in the Haraz (Iran) catchment,
indicating higher bioavailability and potential human and ecological health
concerns (where higher values of CSUS/CW are considered as a risk indicator).
PMID- 29342205
TI - Correction: Cholecystectomy can increase the risk of colorectal cancer: A meta
analysis of 10 cohort studies.
AB - [This corrects the article DOI: 10.1371/journal.pone.0181852.].
PMID- 29342207
TI - Prognosis of chronic kidney disease with normal-range proteinuria: The CKD-ROUTE
study.
AB - BACKGROUND: Although lower estimated glomerular filtration rate (eGFR) and higher
proteinuria are high risks for mortality and kidney outcomes, the prognosis of
chronic kidney disease (CKD) in patients with normal-range proteinuria remains
unclear. METHODS: In this prospective cohort study, 1138 newly visiting stage G2
G5 CKD patients were stratified into normal-range and abnormal-range proteinuria
groups. Study endpoints were CKD progression (>50% eGFR loss or initiation of
dialysis), cardiovascular events, and all-cause death. RESULTS: In total, 927
patients who were followed for >6 months were included in the analysis. The mean
age was 67 years, and 70.2% were male. During a median follow-up of 35 months,
CKD progression, cardiovascular events, and mortality were observed in 223, 110,
and 55 patients, respectively. Patients with normal-range proteinuria had a
significantly lower risk for CKD progression (hazard ratio, 0.20; 95% confidence
interval, 0.10-0.38) than those with abnormal-proteinuria by multivariate Cox
proportional hazard analysis. We also analyzed patients with normal-range
proteinuria (n = 351). Nephrosclerosis was the most frequent cause of CKD among
all patients with normal-range proteinuria (59.7%). During a median follow-up of
36 months, CKD progression, cardiovascular events, and mortality were observed in
10, 28, and 18 patients, respectively. The Kaplan-Meyer analysis demonstrated
that the risks of CKD progression and cardiovascular events were not
significantly different among CKD stages, whereas the risk of death was
significantly higher in patients with advanced-stage CKD. Multivariate Cox
proportional hazard analysis showed that the risk of three endpoints did not
significantly differ among CKD stages. CONCLUSION: Newly visiting CKD patients
with normal-range proteinuria, who tend to be overlooked during health checkups
did not exhibit a decrease in kidney function even in advanced CKD stages under
specialized nephrology care.
PMID- 29342206
TI - Silymarin prevents acetaminophen-induced hepatotoxicity in mice.
AB - Acetaminophen or paracetamol (APAP) overdose is a common cause of liver injury.
Silymarin (SLM) is a hepatoprotective agent widely used for treating liver injury
of different origin. In order to evaluate the possible beneficial effects of SLM,
Balb/c mice were pretreated with SLM (100 mg/kg b.wt. per os) once daily for
three days. Two hours after the last SLM dose, the mice were administered APAP
(300 mg/kg b.wt. i.p.) and killed 6 (T6), 12 (T12) and 24 (T24) hours later. SLM
treated mice exhibited a significant reduction in APAP-induced liver injury,
assessed according to AST and ALT release and histological examination. SLM
treatment significantly reduced superoxide production, as indicated by lower GSSG
content, lower HO-1 induction, alleviated nitrosative stress, decreased p-JNK
activation and direct measurement of mitochondrial superoxide production in
vitro. SLM did not affect the APAP-induced decrease in CYP2E1 activity and
expression during the first 12 hrs. Neutrophil infiltration and enhanced
expression of inflammatory markers were first detected at T12 in both groups.
Inflammation progressed in the APAP group at T24 but became attenuated in SLM
treated animals. Histological examination suggests that necrosis the dominant
cell death pathway in APAP intoxication, which is partially preventable by SLM
pretreatment. We demonstrate that SLM significantly protects against APAP-induced
liver damage through the scavenger activity of SLM and the reduction of
superoxide and peroxynitrite content. Neutrophil-induced damage is probably
secondary to necrosis development.
PMID- 29342208
TI - Comparison of traffic-injury related hospitalisation between bicyclists and
motorcyclists in Taiwan.
AB - OBJECTIVES: Bicyclists and motorcyclists contribute substantially to the
morbidity and mortality rates of road crash casualties. The objective of the
study was to investigate the crash characteristics of bicyclist and motorcyclist
casualties presented to hospitals in Taiwan resulting from crashes. METHODS: By
using linked data from The National Traffic Crash Dataset and the National Health
Insurance Database between 2003 and 2012, logistic regression models were used to
examine the determinants of hospitalisation among motorcyclist and bicyclist
casualties. The examined variables include demographic characteristics, road and
weather conditions, and vehicle characteristics. RESULTS: A total of 1,998,606
two-wheelers were enrolled in the study, of whom 216,600 were hospitalised:
203,623 were motorcyclists and 12,964 were bicyclists. Bicyclists were more
likely to be hospitalised than motorcyclists were (14.0% vs. 10.7%). The pooled
logistic regression model shows that bicyclists had higher odds of
hospitalisation than motorcyclists (adjusted odds ratio [AOR] = 1.11, 95%
confident interval [CI] = 1.08-1.14). In the motorcyclist and bicyclist models,
helmet non-use appears to be a determinant of hospitalisation for motorcyclists
(AOR = 1.14, CI = 1.12-1.16), although insignificant for cyclists (AOR = 1.03, CI
= 0.94-1.12). Other important determinants of hospitalisation for motorcyclists
and cyclists include female riders, elderly riders, rural roadways, unlicensed
riding (for motorcyclists only), curved roadways, defective roadways, alcohol
consumption (only for motorcyclists), and single-vehicle crashes (for
motorcyclists only). CONCLUSIONS: The result that bicyclists had an increased
probability of being hospitalised than motorcyclists is particularly noteworthy,
because there have recently been much more users of bikesharing systems in
metropolitan cities where cycle helmets are not provided. We further found that
helmet non-use was also a risk factor for motorcyclists, but insignificant for
cyclists, possibly due to lower helmet utilization rates among bicyclists. Our
findings regarding the increased hospitalisation percentage emphasize the
importance of helmet use.
PMID- 29342209
TI - Correction: Harmonizing the pixel size in retrospective computed tomography
radiomics studies.
AB - [This corrects the article DOI: 10.1371/journal.pone.0178524.].
PMID- 29342210
TI - Effects of theory of mind performance training on reducing bullying involvement
in children and adolescents with high-functioning autism spectrum disorder.
AB - Bullying involvement is prevalent among children and adolescents with autism
spectrum disorder (ASD). This study examined the effects of theory of mind
performance training (ToMPT) on reducing bullying involvement in children and
adolescents with high-functioning ASD. Children and adolescents with high
functioning ASD completed ToMPT (n = 26) and social skills training (SST; n = 23)
programs. Participants in both groups and their mothers rated the pretraining and
posttraining bullying involvement of participants on the Chinese version of the
School Bullying Experience Questionnaire. The paired t test was used to evaluate
changes in bullying victimization and perpetration between the pretraining and
posttraining assessments. Furthermore, the linear mixed-effect model was used to
examine the difference in the training effect between the ToMPT and SST groups.
The paired t test indicated that in the ToMPT group, the severities of both self
reported (p = .039) and mother-reported (p = .003) bullying victimization
significantly decreased from the pretraining to posttraining assessments, whereas
in the SST group, only self-reported bullying victimization significantly
decreased (p = .027). The linear mixed-effect model indicated that compared with
the SST program, the ToMPT program significantly reduced the severity of mother
reported bullying victimization (p = .041). The present study supports the
effects of ToMPT on reducing mother-reported bullying victimization in children
and adolescents with high-functioning ASD.
PMID- 29342211
TI - Correction: A Meta-Analysis of the Association between ESR1 Genetic Variants and
the Risk of Breast Cancer.
AB - [This corrects the article DOI: 10.1371/journal.pone.0153314.].
PMID- 29342214
TI - Correction: Large-Scale Diversity of Slope Fishes: Pattern Inconsistency between
Multiple Diversity Indices.
AB - [This corrects the article DOI: 10.1371/journal.pone.0066753.].
PMID- 29342212
TI - Sequence variation in Plasmodium falciparum merozoite surface protein-2 is
associated with virulence causing severe and cerebral malaria.
AB - Parasite virulence, an important factor contributing to the severity of
Plasmodium falciparum infection, varies among P. falciparum strains. Relatively
little is known regarding markers of virulence capable of identifying strains
responsible for severe malaria. We investigated the effects of genetic variations
in the P.f. merozoite surface protein 2 gene (msp2) on virulence, as it was
previously postulated as a factor. We analyzed 300 msp2 sequences of single P.
falciparum clone infection from patients with uncomplicated disease as well as
those admitted for severe malaria with and without cerebral disease. The
association of msp2 variations with disease severity was examined. We found that
the N allele at codon 8 of Block 2 in the FC27-like msp2 gene was significantly
associated with severe disease without cerebral complications (odds ratio = 2.73,
P = 0.039), while the K allele at codon 17 of Block 4 in the 3D7-like msp2 gene
was associated with cerebral malaria (odds ratio = 3.52, P = 0.024). The data
suggests possible roles for the associated alleles on parasite invasion processes
and immune-mediated pathogenicity. Multiplicity of infection was found to
associate with severe disease without cerebral complications, but not cerebral
malaria. Variations in the msp2-FC27-block 2-8N and 3D7-block 4-17K allele appear
to be parasite virulence markers, and may be useful in determining the likelihood
for severe and cerebral malaria. Their interactions with potential host factors
for severe diseases should also be explored.
PMID- 29342213
TI - Circulating neutrophil transcriptome may reveal intracranial aneurysm signature.
AB - BACKGROUND: Unruptured intracranial aneurysms (IAs) are typically asymptomatic
and undetected except for incidental discovery on imaging. Blood-based diagnostic
biomarkers could lead to improvements in IA management. This exploratory study
examined circulating neutrophils to determine whether they carry RNA expression
signatures of IAs. METHODS: Blood samples were collected from patients receiving
cerebral angiography. Eleven samples were collected from patients with IAs and 11
from patients without IAs as controls. Samples from the two groups were paired
based on demographics and comorbidities. RNA was extracted from isolated
neutrophils and subjected to next-generation RNA sequencing to obtain
differential expressions for identification of an IA-associated signature.
Bioinformatics analyses, including gene set enrichment analysis and Ingenuity
Pathway Analysis, were used to investigate the biological function of all
differentially expressed transcripts. RESULTS: Transcriptome profiling identified
258 differentially expressed transcripts in patients with and without IAs.
Expression differences were consistent with peripheral neutrophil activation. An
IA-associated RNA expression signature was identified in 82 transcripts (p<0.05,
fold-change >=2). This signature was able to separate patients with and without
IAs on hierarchical clustering. Furthermore, in an independent, unpaired,
replication cohort of patients with IAs (n = 5) and controls (n = 5), the 82
transcripts separated 9 of 10 patients into their respective groups. CONCLUSION:
Preliminary findings show that RNA expression from circulating neutrophils
carries an IA-associated signature. These findings highlight a potential to use
predictive biomarkers from peripheral blood samples to identify patients with
IAs.
PMID- 29342215
TI - Correction: Seventy Years of Asthma in Italy: Age, Period and Cohort Effects on
Incidence and Remission of Self-Reported Asthma from 1940 to 2010.
AB - [This corrects the article DOI: 10.1371/journal.pone.0138570.].
PMID- 29342216
TI - In Vitro activity of novel glycopolymer against clinical isolates of multidrug
resistant Staphylococcus aureus.
AB - The incidence of multidrug-resistant (MDR) organisms, including methicillin
resistant Staphylococcus aureus (MRSA), is a serious threat to public health.
Progress in developing new therapeutics is being outpaced by antibiotic
resistance development, and alternative agents that rapidly permeabilize bacteria
hold tremendous potential for treating MDR infections. A new class of
glycopolymers includes polycationic poly-N (acetyl, arginyl) glucosamine (PAAG)
is under development as an alternative to traditional antibiotic strategies to
treat MRSA infections. This study demonstrates the antibacterial activity of PAAG
against clinical isolates of methicillin and mupirocin-resistant Staphylococcus
aureus. Multidrug-resistant S. aureus was rapidly killed by PAAG, which
completely eradicated 88% (15/17) of all tested strains (6-log reduction in CFU)
in <= 12-hours at doses that are non-toxic to mammalian cells. PAAG also
sensitized all the clinical MRSA strains (17/17) to oxacillin as demonstrated by
the observed reduction in the oxacillin MIC to below the antibiotic resistance
breakpoint. The effect of PAAG and standard antibiotics including vancomycin,
oxacillin, mupirocin and bacitracin on MRSA permeability was studied by measuring
propidium iodide (PI) uptake by bacterial cells. Antimicrobial resistance studies
showed that S. aureus developed resistance to PAAG at a rate slower than to
mupirocin but similar to bacitracin. PAAG was observed to resensitize drug
resistant S. aureus strains sampled from passage 13 and 20 of the multi-passage
resistance study, reducing MICs of mupirocin and bacitracin below their clinical
sensitivity breakpoints. This class of bacterial permeabilizing glycopolymers may
provide a new tool in the battle against multidrug-resistant bacteria.
PMID- 29342217
TI - How do the outcomes of the DEKA Arm compare to conventional prostheses?
AB - OBJECTIVES: Objectives were to 1) compare self-reported function, dexterity,
activity performance, quality of life and community integration of the DEKA Arm
to conventional prostheses; and 2) examine differences in outcomes by
conventional prosthesis type, terminal device type and by DEKA Arm configuration
level. METHODS: This was a two-part study; Part A consisted of in-laboratory
training. Part B consisted of home use. Study participants were 23 prosthesis
users (mean age = 45 +/- 16; 87% male) who completed Part A, and 15 (mean age =
45 +/- 18; 87% male) who completed Parts A and B. Outcomes including self-report
and performance measures, were collected at Baseline using participants' personal
prostheses and at the End of Parts A and B. Scores were compared using paired t
tests. Wilcoxon signed-rank tests were used to compare outcomes for the full
sample, and for the sample stratified by device and terminal device type.
Analysis of outcomes by configuration level was performed graphically. RESULTS:
At the End of Part A activity performance using the DEKA Arm and conventional
prosthesis was equivalent, but slower with the DEKA Arm. After Part B,
performance using the DEKA Arm surpassed conventional prosthesis scores, and
speed of activity completion was equivalent. Participants reported using the DEKA
Arm to perform more activities, had less perceived disability, and less
difficulty in activities at the End of A and B as compared to Baseline. No
differences were observed in dexterity, prosthetic skill, spontaneity, pain,
community integration or quality of life. Comparisons stratified by device type
revealed similar patterns. Graphic comparisons revealed variations by
configuration level. CONCLUSION: Participants using the DEKA Arm had less
perceived disability and more engagement of the prosthesis in everyday tasks,
although activity performance was slower. After home use experience, activity
performance was improved and activity speed equivalent to using conventional
prostheses.
PMID- 29342218
TI - Cross-lagged structural equation models for the relationship between health
related state and behaviours and body bullying in adolescence: findings from
longitudinal study ELANA.
AB - We investigated the stability and the directionality of being body bullied and a
set of four variables- 1) Body Mass Index (BMI), 2) moderate and vigorous
physical activity (MVPA), 3) television time (TV) and 4) video game/computer time
(VG)-, termed in the present study as 'health-related state and behaviours
(HRSB)'-across adolescence. The Adolescent Nutritional Assessment Longitudinal
Study (ELANA) is a cohort study conducted among middle school students from two
public and four private schools in Rio de Janeiro-Brazil. We analysed data from
2010 (T1) and 2012 (T2) among 810 adolescents (aged 9-15 at T1). Gender-specific
structural equation models (SEM) were estimated, including autoregressive paths
for the HRSB and being body bullied over time, correlations at T1 and T2,
respectively, and cross-lagged effects. The results presented significant
stability coefficients for almost all variables over time in both genders (except
for MVPA in boys and girls and TV time among girls). There were positive
correlations between BMI and being body bullied, as well as between TV and VG for
boys (0.32, p<0.001 and 0.24, p<0.001, respectively) and girls (0.30, p<0.001 and
0.30, p<0.001, respectively) at T1. It remained significant at T2 (boys: 0.18,
p<0.05 and 0.16, p<0.01; girls: 0.21, p<0.01 and 0.22, p<0.01, respectively).
Examining the cross-lagged paths between being body bullied and HRSB, we observed
that the reciprocal model provided the best fit for boys, indicating that BMI at
T1 had a significant effect in being body bullied at T2 (0.12, p<0.05) and being
body bullied at T1 had an effect on VG at T2 (0.14, p<0.01). Among girls the
forward causation model showed the best fit, demonstrating a significant effect
of being body bullied at T1 on VG at T2 (0.16, p<0.01). Apart from MVPA, both
being body bullying and HRSB were largely stable across adolescence. For boys and
girls alike, exposure to being body bullied seemed to increase their time spent
on VG, while for boys BMI also predicted being body bullied. This study
highlighted the complex interplay between being body bullied and HRSB and the
importance of acknowledging gender differences in this context.
PMID- 29342220
TI - Correction: IFNAR2-dependent gene expression profile induced by IFN-alpha in
Pteropus alecto bat cells and impact of IFNAR2 knockout on virus infection.
AB - [This corrects the article DOI: 10.1371/journal.pone.0182866.].
PMID- 29342219
TI - The expression profile and prognostic significance of eukaryotic translation
elongation factors in different cancers.
AB - Eukaryotic translation factors, especially initiation factors have garnered much
attention with regards to their role in the onset and progression of different
cancers. However, the expression levels and prognostic significance of
translation elongation factors remain poorly explored in different cancers. In
this study, we have investigated the mRNA transcript levels of seven translation
elongation factors in different cancer types using Oncomine and TCGA databases.
Furthermore, we have identified the prognostic significance of these factors
using Kaplan-Meier Plotter and SurvExpress databases. We observed altered
expression levels of all the elongation factors in different cancers. Higher
expression of EEF1A2, EEF1B2, EEF1G, EEF1D, EEF1E1 and EEF2 was observed in most
of the cancer types, whereas reverse trend was observed for EEF1A1.
Overexpression of many factors predicted poor prognosis in breast (EEF1D, EEF1E1,
EEF2) and lung cancer (EEF1A2, EEF1B2, EEF1G, EEF1E1). However, we didn't see any
common correlation of expression levels of elongation factors with survival
outcomes across cancer types. Cancer subtype stratification showed association of
survival outcomes and expression levels of elongation factors in specific sub
types of breast, lung and gastric cancer. Most interestingly, we observed a
reciprocal relationship between the expression levels of the two EEF1A isoforms
viz. EEF1A1 and EEF1A2, in most of the cancer types. Our results suggest that
translation elongation factors can have a role in tumorigenesis and affect
survival in cancer specific manner. Elongation factors have potential to serve as
biomarkers and therapeutic drug targets, yet further study is required.
Reciprocal relationship of differential expression between EEF1A isoforms
observed in multiple cancer types indicates opposing roles in cancer and needs
further investigation.
PMID- 29342221
TI - Genotype-by-environment interactions affecting heterosis in maize.
AB - The environment can influence heterosis, the phenomena in which the offspring of
two inbred parents exhibits phenotypic performance beyond the inbred parents for
specific traits. In this study we measured 25 traits in a set of 47 maize hybrids
and their inbred parents grown in 16 different environments with varying levels
of average productivity. By quantifying 25 vegetative and reproductive traits
across the life cycle we were able to analyze interactions between the
environment and multiple distinct instances of heterosis. The magnitude and rank
among hybrids for better-parent heterosis (BPH) varied for the different traits
and environments. Across the traits, a higher within plot variance was observed
for inbred lines compared to hybrids. However, for most traits, variance across
environments was not significantly different for inbred lines compared to
hybrids. Further, for many traits the correlations of BPH to hybrid performance
and BPH to better parent performance were of comparable magnitude. These results
indicate that inbred lines and hybrids show similar trends in environmental
response and both are contributing to observed genotype-by-environment
interactions for heterosis. This study highlights the degree of heterosis is not
an inherent trait of a specific hybrid, but varies depending on the trait
measured and the environment where that trait is measured. Studies that attempt
to correlate molecular processes with heterosis are hindered by the fact that
heterosis is not a consistent attribute of a specific hybrid.
PMID- 29342223
TI - Development of a Job Exposure Matrix for Noise in the Swedish Soft Tissue Paper
Industry.
AB - Objectives: Noise exposure is a common occupational hazard, but has not been
sufficiently characterized in paper mills. We developed a job-exposure matrix
(JEM) for noise exposure for use in estimating exposures among Swedish soft
tissue paper mill workers. Methods: We used a combination of area and personal
dosimetry noise exposure measurements made at four soft tissue paper mills by
industry and research staff between 1977 and 2013 to estimate noise exposures by
department, location, and job title. We then utilized these estimates, in
conjunction with information on process and facility changes and use of hearing
protection collected via focus groups, to create a seven-category, semi
quantitative JEM for all departments, locations, and job titles spanning the
years 1940-2010. Results: The results of the 1157 area and personal dosimetry
noise measurements indicated that noise levels have generally declined in Swedish
paper mills over time, though these changes have been neither uniform nor
monotonic within or across the four mills. Focus group results indicated that use
of hearing protection has generally increased over time. The noise JEM totals
1917 cells, with each cell representing a unique combination of operation, job
title, and single year. We estimated that ~50% of workers at the four mills
assessed were exposed at or above the Swedish 8-h average noise exposure limit of
an 85 dBA at the conclusion of the study period in 2010. Conclusions: Our results
highlight the continuing need for hearing loss prevention and noise control
efforts at these and similar mills, and the completed JEM now represents a tool
for use in epidemiological studies of noise-related health outcomes.
PMID- 29342222
TI - Mechano-electric feedback effects in a three-dimensional (3D) model of the
contracting cardiac ventricle.
AB - Mechano-electric feedback affects the electrophysiological and mechanical
function of the heart and the cellular, tissue, and organ properties. To
determine the main factors that contribute to this effect, this study
investigated the changes in the action potential characteristics of the ventricle
during contraction. A model of stretch-activated channels was incorporated into a
three-dimensional multiscale model of the contracting ventricle to assess the
effect of different preload lengths on the electrophysiological behavior. The
model describes the initiation and propagation of the electrical impulse, as well
as the passive (stretch) and active (contraction) changes in the cardiac
mechanics. Simulations were performed to quantify the relationship between the
cellular activation and recovery patterns as well as the action potential
durations at different preload lengths in normal and heart failure pathological
conditions. The simulation results showed that heart failure significantly
affected the excitation propagation parameters compared to normal condition. The
results showed that the mechano-electrical feedback effects appear to be most
important in failing hearts with low ejection fraction.
PMID- 29342224
TI - Elabela-APJ axis contributes to embryonic development and prevents pre-eclampsia
in pregnancy.
PMID- 29342225
TI - RE: "DIETARY INTAKE OF ANTIOXIDANT VITAMINS AND CAROTENOIDS AND RISK OF
DEVELOPING ACTIVE TUBERCULOSIS IN A PROSPECTIVE POPULATION-BASED COHORT".
PMID- 29342226
TI - Don't Judge a Book by its Cover: Examiner Expectancy Effects Predict
Neuropsychological Performance for Individuals Judged as Chronic Cannabis Users.
AB - Objective: The experimenter expectancy effect confound remains largely unexplored
in neuropsychological research and has never been investigated among cannabis
users. This study investigated whether examiner expectancies of cannabis user
status affected examinees' neuropsychological performance. Method: Participants
included 41 cannabis users and 20 non-users. Before testing, examiners who were
blind to participant user status privately rated whether they believed the
examinee was a cannabis user or non-user. Examiners then administered a battery
of neuropsychological and performance validity measures. Multiple regression
analyses compared performance between examinees judged as cannabis users (n = 37)
and those judged as non-users (n = 24). Results: Examiners' judgments of cannabis
users were 75% accurate; judgments of non-users were at chance. After controlling
for age, gender, and actual user status, examiner judgments of cannabis user
status predicted performance on two measures (California Verbal Learning Test-II,
and Trail Making Test B; p < .05), as individuals judged as cannabis users
obtained lower scores than those judged as non-users. Conclusions: Examiners'
judgments of cannabis user status predicted performance even after controlling
for actual user status, indicating vulnerability to examiner expectancy effects.
These findings have important implications for both research and clinical
settings, as scores may partially reflect examiners' expectations regarding
cannabis effects rather than participants' cognitive abilities. These results
demonstrate the need for expectancy effect research in the neuropsychological
assessment of all populations, not just cannabis users.
PMID- 29342227
TI - Brain Cytosolic Phospholipase A2alpha Mediates Angiotensin II-Induced
Hypertension and Reactive Oxygen Species Production in Male Mice.
AB - BACKGROUND: Recently, we reported that angiotensin II (Ang II)-induced
hypertension is mediated by group IV cytosolic phospholipase A2alpha (cPLA2alpha)
via production of prohypertensive eicosanoids. Since Ang II increases blood
pressure (BP) via its action in the subfornical organ (SFO), it led us to
investigate the expression and possible contribution of cPLA2alpha to oxidative
stress and development of hypertension in this brain area. METHODS: Adenovirus
(Ad)-green fluorescence protein (GFP) cPLA2alpha short hairpin (sh) RNA (Ad
cPLA2alpha shRNA) and its control Ad-scrambled shRNA (Ad-Scr shRNA) or Ad
enhanced cyan fluorescence protein cPLA2alpha DNA (Ad-cPLA2alpha DNA) and its
control Ad-GFP DNA were transduced into SFO of cPLA2alpha+/+ and cPLA2alpha-/-
male mice, respectively. Ang II (700 ng/kg/min) was infused for 14 days in these
mice, and BP was measured by tail-cuff and radio telemetry. cPLA2 activity,
reactive oxygen species production, and endoplasmic reticulum stress were
measured in the SFO. RESULTS: Transduction of SFO with Ad-cPLA2alpha shRNA, but
not Ad-Scr shRNA in cPLA2alpha+/+ mice, minimized expression of cPLA2alpha, Ang
II-induced cPLA2alpha activity and oxidative stress in the SFO, BP, and cardiac
and renal fibrosis. In contrast, Ad-cPLA2alpha DNA, but not its control Ad-GFP
DNA in cPLA2alpha-/- mice, restored the expression of cPLA2alpha, and Ang II
induced increase in cPLA2 activity and oxidative stress in the SFO, BP, cardiac,
and renal fibrosis. CONCLUSIONS: These data suggest that cPLA2alpha in the SFO is
crucial in mediating Ang II-induced hypertension and associated pathogenesis.
Therefore, development of selective cPLA2alpha inhibitors could be useful in
treating hypertension and its pathogenesis.
PMID- 29342228
TI - Labiaplasty: Indications and Predictors of Postoperative Sequelae in 451
Consecutive Cases.
AB - Background: The increasing demand for labiaplasty is well recognized; however,
the procedure remains contentious. Objectives: We aim to provide a large-scale,
up-to-date analysis of labiaplasty outcomes and factors influencing postoperative
sequelae (POS). Methods: We analyzed a single-center, prospectively maintained
database of females undergoing labiaplasty between 2002 and 2017. Demographic,
procedural, and outcomes' data were retrieved. Binary logistic regressions were
used to evaluate the odds of developing POS (revisional surgery and
complications); presented as odds ratios (OR) with 95% confidence intervals (CI).
Results: Data for 451 consecutive patients were retrieved, ten of whom were <18
years of age. Overall, 86% were Caucasian, mean age was 32.6 years, and 11.8%
were smokers. Concomitant labia majora reduction was performed in 7.3%, and
clitoral hood reduction in 5.8%. There were 32 cases of POS (7.1%), while the
complication rate was 3.8%. Comparing those with POS to those without, there were
no differences in age (32.8 vs 29.9 years, P = 0.210), operative time (78.5 vs
80.6 minutes, P = 0.246), or comorbidities (P > 0.05 for all). On univariable
analysis, increased odds of POS occurred with sexual dysfunction as an indication
for surgery (OR 3.778, CI 1.682-8.483). On subgroup analysis of those >=18 years,
both smoking (2.576, CI 1.044-6.357) and sexual dysfunction as an indication (OR
4.022, CI 1.772-9.131) increased the odds of POS. On multivariable analysis of
the subgroup, sexual dysfunction as an indication persisted in significance (OR
3.850, CI 1.683-8.807). Conclusions: Results compare favorably with previously
reported complication and revisional surgery rates. Smoking and sexual
dysfunction may increase the risk of complications. Level of Evidence 2:
PMID- 29342229
TI - A rapid epistatic mixed-model association analysis by linear retransformations of
genomic estimated values.
AB - Motivation: Epistasis provides a feasible way for probing potential genetic
mechanism of complex traits. However, time-consuming computation challenges
successful detection of interaction in practice, especially when linear mixed
model (LMM) is used to control type I error in the presence of population
structure and cryptic relatedness. Results: A rapid epistatic mixed-model
association analysis (REMMA) method was developed to overcome computational
limitation. This method first estimates individuals' epistatic effects by an
extended genomic best linear unbiased prediction (EG-BLUP) model with additive
and epistatic kinship matrix, then pairwise interaction effects are obtained by
linear retransformations of individuals' epistatic effects. Simulation studies
showed that REMMA could control type I error and increase statistical power in
detecting epistatic QTNs in comparison with existing LMM-based FaST-LMM. We
applied REMMA to two real datasets, a mouse dataset and the Wellcome Trust Case
Control Consortium (WTCCC) data. Application to the mouse data further confirmed
the performance of REMMA in controlling type I error. For the WTCCC data, we
found most epistatic QTNs for type 1 diabetes (T1D) located in a major
histocompatibility complex (MHC) region, from which a large interacting network
with 12 hub genes (interacting with ten or more genes) was established.
Availability and implementation: Our REMMA method can be freely accessed at
https://github.com/chaoning/REMMA. Contact: liujf@cau.edu.cn. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 29342230
TI - Metformin as an anti-cancer agent: actions and mechanisms targeting cancer stem
cells.
AB - Metformin, a first line medication for type II diabetes, initially entered the
spotlight as a promising anti-cancer agent due to epidemiologic reports that
found reduced cancer risk and improved clinical outcomes in diabetic patients
taking metformin. To uncover the anti-cancer mechanisms of metformin, preclinical
studies determined that metformin impairs cellular metabolism and suppresses
oncogenic signaling pathways, including receptor tyrosine kinase, PI3K/Akt, and
mTOR pathways. Recently, the anti-cancer potential of metformin has gained
increasing interest due to its inhibitory effects on cancer stem cells (CSCs),
which are associated with tumor metastasis, drug resistance, and relapse. Studies
using various cancer models, including breast, pancreatic, prostate, and colon,
have demonstrated the potency of metformin in attenuating CSCs through the
targeting of specific pathways involved in cell differentiation, renewal,
metastasis, and metabolism. In this review, we provide a comprehensive overview
of the anti-cancer actions and mechanisms of metformin, including the regulation
of CSCs and related pathways. We also discuss the potential anti-cancer
applications of metformin as mono- or combination therapies.
PMID- 29342232
TI - Informational and linguistic analysis of large genomic sequence collections via
efficient Hadoop cluster algorithms.
AB - Motivation: Information theoretic and compositional/linguistic analysis of
genomes have a central role in bioinformatics, even more so since the associated
methodologies are becoming very valuable also for epigenomic and meta-genomic
studies. The kernel of those methods is based on the collection of k-mer
statistics, i.e. how many times each k-mer in {A,C,G,T}k occurs in a DNA
sequence. Although this problem is computationally very simple and efficiently
solvable on a conventional computer, the sheer amount of data available now in
applications demands to resort to parallel and distributed computing. Indeed,
those type of algorithms have been developed to collect k-mer statistics in the
realm of genome assembly. However, they are so specialized to this domain that
they do not extend easily to the computation of informational and linguistic
indices, concurrently on sets of genomes. Results: Following the well-established
approach in many disciplines, and with a growing success also in bioinformatics,
to resort to MapReduce and Hadoop to deal with 'Big Data' problems, we present
KCH, the first set of MapReduce algorithms able to perform concurrently
informational and linguistic analysis of large collections of genomic sequences
on a Hadoop cluster. The benchmarking of KCH that we provide indicates that it is
quite effective and versatile. It is also competitive with respect to the
parallel and distributed algorithms highly specialized to k-mer statistics
collection for genome assembly problems. In conclusion, KCH is a much needed
addition to the growing number of algorithms and tools that use MapReduce for
bioinformatics core applications. Availability and implementation: The software,
including instructions for running it over Amazon AWS, as well as the datasets
are available at http://www.di-srv.unisa.it/KCH. Contact:
umberto.ferraro@uniroma1.it. Supplementary information: Supplementary data are
available at Bioinformatics online.
PMID- 29342231
TI - Mapping gene regulatory networks from single-cell omics data.
AB - Single-cell techniques are advancing rapidly and are yielding unprecedented
insight into cellular heterogeneity. Mapping the gene regulatory networks (GRNs)
underlying cell states provides attractive opportunities to mechanistically
understand this heterogeneity. In this review, we discuss recently emerging
methods to map GRNs from single-cell transcriptomics data, tackling the challenge
of increased noise levels and data sparsity compared with bulk data, alongside
increasing data volumes. Next, we discuss how new techniques for single-cell
epigenomics, such as single-cell ATAC-seq and single-cell DNA methylation
profiling, can be used to decipher gene regulatory programmes. We finally look
forward to the application of single-cell multi-omics and perturbation techniques
that will likely play important roles for GRN inference in the future.
PMID- 29342234
TI - Stability-Indicating HPLC and HPTLC Methods for Determination of Agomelatine and
its Degradation Products.
AB - Two accurate, sensitive and highly selective stability-indicating methods are
developed and validated for simultaneous determination of Agomelatine (AGM) and
its forced degradation products (Deg I and II). The first method is High
Performance Liquid Chromatography for separation and quantitation of AGM, Deg I
and II on a C18 column (250 mm * 4.6 mm, 5 MUm p.s) in isocratic mode by using a
binary mixture of Potassium dihydrogen phosphate (0.05 M, pH adjusted to 2.9 with
orthophosphoric acid): acetonitrile (60:40, v/v) at a flow rate of 2 mL/min. The
components were detected at 230 nm over a concentration range of 0.5-10 MUg/mL
for AGM and 0.5-5 MUg/mL for both Deg I and II. The second method is High
Performance Thin-Layer Chromatography, where AGM, Deg I and II were separated on
silica gel HPTLC F254 plates using chloroform:methanol:ammonia solution (9:1:0.1,
by volume) as a developing system. The separated bands were scanned at 230 nm
over the concentration range of 0.2-1.2 MUg/band for AGM in pure form and human
plasma and 0.1-1 MUg/band for both Deg I and II. The proposed methods were
successfully applied for analysis of AGM in pharmaceutical formulations. The
results obtained by the proposed methods were statistically compared to the
reported HPLC method revealing high accuracy and good precision.
PMID- 29342233
TI - QuantumClone: clonal assessment of functional mutations in cancer based on a
genotype-aware method for clonal reconstruction.
AB - Motivation: In cancer, clonal evolution is assessed based on information coming
from single nucleotide variants and copy number alterations. Nonetheless,
existing methods often fail to accurately combine information from both sources
to truthfully reconstruct clonal populations in a given tumor sample or in a set
of tumor samples coming from the same patient. Moreover, previously published
methods detect clones from a single set of variants. As a result, compromises
have to be done between stringent variant filtering [reducing dispersion in
variant allele frequency estimates (VAFs)] and using all biologically relevant
variants. Results: We present a framework for defining cancer clones using most
reliable variants of high depth of coverage and assigning functional mutations to
the detected clones. The key element of our framework is QuantumClone, a method
for variant clustering into clones based on VAFs, genotypes of corresponding
regions and information about tumor purity. We validated QuantumClone and our
framework on simulated data. We then applied our framework to whole genome
sequencing data for 19 neuroblastoma trios each including constitutional,
diagnosis and relapse samples. We confirmed an enrichment of damaging variants
within such pathways as MAPK (mitogen-activated protein kinases), neuritogenesis,
epithelial-mesenchymal transition, cell survival and DNA repair. Most pathways
had more damaging variants in the expanding clones compared to shrinking ones,
which can be explained by the increased total number of variants between these
two populations. Functional mutational rate varied for ancestral clones and
clones shrinking or expanding upon treatment, suggesting changes in clone
selection mechanisms at different time points of tumor evolution. Availability
and implementation: Source code and binaries of the QuantumClone R package are
freely available for download at https://CRAN.R-project.org/package=QuantumClone.
Contact: gudrun.schleiermacher@curie.fr or valentina.boeva@inserm.fr.
Supplementary information: Supplementary data are available at Bioinformatics
online.
PMID- 29342235
TI - Estimation of Lead Exposure Prevalence in Korean Population through Combining
Multiple Experts' Judgment based on Objective Data Sources.
AB - Objective: Estimating carcinogen exposure prevalence is important for preventing
occupational cancers. To develop the Korean version of CARcinogen EXposure
(CAREX), a carcinogen surveillance system used in many countries, we estimated
lead exposure prevalence in the Korean working population. Methods: We used three
Korean nationwide data sources to obtain objective database-derived prevalences
of lead exposure across industries: airborne lead measurement data from the work
environment measurement database (WEMD), blood lead measurement data from the
special health examination database (SHED), and lead exposure prevalence computed
using data from the work environment condition survey (WECS), which is a
nationwide occupational exposure survey. We also asked a panel of 52 experts with
>=20 years of experience in industrial hygiene practice for their judgment about
lead exposure prevalence across industries after they reviewed the database
derived prevalences computed from the three exposure databases. We developed and
compared various estimation methods for combining the experts' judgments. The
2010 census was used as the reference population to estimate the number of lead
exposed workers in 228 industries by multiplying the exposure prevalence by the
number of workers in each industry. Results: The database-derived prevalences of
lead exposure in the 228 industries were calculated using data collected between
2009 and 2011 from the WEMD and SHED and from the 2009 WECS. From the various
estimation methods assessed, the median values of experts' responses were
selected as our estimates of lead exposure prevalence in each industry. As a
result, it was estimated that 129,250 Korean workers were exposed to lead in
2010. Conclusions: Based on objective databases, we developed a method for
estimating exposure prevalence for the CAREX system by combining experts'
judgments. This work may offer an unbiased approach to the development process
that accounts for the uncertainty in exposure.
PMID- 29342236
TI - MAGNAMWAR: an R package for genome-wide association studies of bacterial
orthologs.
AB - Summary: Here we report on an R package for genome-wide association studies of
orthologous genes in bacteria. Before using the software, orthologs from
bacterial genomes or metagenomes are defined using local or online
implementations of OrthoMCL. These presence-absence patterns are statistically
associated with variation in user-collected phenotypes using the Mono-Associated
GNotobiotic Animals Metagenome-Wide Association R package (MAGNAMWAR). Genotype
phenotype associations can be performed with several different statistical tests
based on the type and distribution of the data. Availability and implementation:
MAGNAMWAR is available on CRAN. Contact: john_chaston@byu.edu.
PMID- 29342237
TI - The Roles of Subdivisions of Human Insula in Emotion Perception and Auditory
Processing.
AB - Previous studies have shown insular activations involving sensory, motor, and
affective processing. However, the functional roles of subdivisions within the
human insula are still not well understood. In the present study, we used
intracranial electroencephalography and electrical cortical stimulation to
investigate the causal roles of subdivisions of the insula in auditory emotion
perception in epilepsy patients implanted with depth electrodes in this brain
region. The posterior and the anterior subdivisions of the human insula,
identified based on structural and functional analyses, showed distinct response
properties to auditory emotional stimuli. The posterior insula showed auditory
responses that resemble those observed in Heschl's gyrus, whereas the anterior
insula (AI) responded to the emotional contents of the auditory stimuli in a
similar way as observed in the amygdala. Furthermore, the degree of the
differentiation between various emotion types increased from the posterior to the
AI. Our findings suggest different roles played by the two regions of the human
insula and a transformation from sensory to affective representations in auditory
modality along the posterior-to-anterior axis in the human insula.
PMID- 29342238
TI - Rhythmic Spontaneous Activity Mediates the Age-Related Decline in Somatosensory
Function.
AB - Sensory gating is a neurophysiological process whereby the response to a second
stimulus in a pair of identical stimuli is attenuated, and it is thought to
reflect the capacity of the CNS to preserve neural resources for behaviorally
relevant stimuli. Such gating is observed across multiple sensory modalities and
is modulated by age, but the mechanisms involved are not understood. In this
study, we examined somatosensory gating in 68 healthy adults using
magnetoencephalography (MEG) and advanced oscillatory and time-domain analysis
methods. MEG data underwent source reconstruction and peak voxel time series data
were extracted to evaluate the dynamics of somatosensory gating, and the impact
of spontaneous neural activity immediately preceding the stimulation. We found
that gating declined with increasing age and that older adults had significantly
reduced gating relative to younger adults, suggesting impaired local inhibitory
function. Most importantly, older adults had significantly elevated spontaneous
activity preceding the stimulation, and this effect fully mediated the impact of
aging on sensory gating. In conclusion, gating in the somatosensory system
declines with advancing age and this effect is directly tied to increased
spontaneous neural activity in the primary somatosensory cortices, which is
likely secondary to age-related declines in local GABA inhibitory function.
PMID- 29342239
TI - HPLC Estimation, Ex vivo Everted Sac Permeability and In Vivo Pharmacokinetic
Studies of Darunavir.
AB - Darunavir ethanolate (DRV) is an efficient protease inhibitor (PI) used in the
treatment of human immunodeficiency virus (HIV) type-1 patients. An isocratic
reversed-phase HPLC method was developed to monitor concentration of darunavir in
in vitro intestinal fluid samples in everted sac absorption model in the presence
of bioenhancers, viz., piperine, quercetin, naringenin. The method was validated
and successfully applied to everted sac and pharmacokinetic studies in rats. The
absorption profiles of DRV and apparent permeability coefficients were
determined. The proposed method was found to be simple, rapid, robust and
selective and was applied for continuous ex vivo monitoring of DRV in everted sac
absorption studies. Of the three bioenhancers screened at different
concentrations, piperine caused highest and significant 1.5-fold increase in
apparent permeability of DRV across everted sac tissue. Further, co
administration of piperine significantly increased the maximum plasma
concentration of DRV by 1.18-fold confirming the enhancement in its absorption.
PMID- 29342240
TI - Presence of Myocardial Damage Predicts Future Development of Hypertension in a
Normotensive Japanese General Population: The Yamagata (Takahata) Study.
AB - BACKGROUND: A modest rise in blood pressure (BP) reportedly increases
cardiovascular mortality despite not reaching obvious hypertension, suggesting
that target organ damages are latently induced by slight BP rising. The goal of
this study was to determine whether presence of subclinical myocardial damage can
predict the future development of hypertension in the normotensive general
population. METHODS AND RESULTS: The cohort study was conducted with subjects who
participated in a community-based annual health check. Normotensive subjects
without prior cardiovascular diseases at baseline were eligible for analyses (n =
524, mean age 58 +/- 9 years; 53% women). We measured heart-type fatty acid
binding protein (H-FABP) at baseline as a biomarker of ongoing myocardial damage.
Longitudinal changes in BP were examined during median follow-up period of 6.2
years, and we investigated the association between the baseline H-FABP level and
longitudinal BP changes. RESULTS: During the follow-up, 177 subjects (34%)
developed hypertension. In multivariate Cox proportional hazard analysis adjusted
for potential confounders including age and baseline BP, presence of myocardial
damage was significantly associated with the development of hypertension (hazard
ratio 1.80, 95% confidence interval, 1.26-2.54; P = 0.0014). Furthermore,
relative risk of myocardial damage for incident hypertension was higher in
younger subjects and lower BP category. CONCLUSIONS: Presence of subclinical
myocardial damage was independently associated with the future development of
hypertension in the normotensive general population.
PMID- 29342241
TI - iPat: intelligent prediction and association tool for genomic research.
AB - Summary: The ultimate goal of genomic research is to effectively predict
phenotypes from genotypes so that medical management can improve human health and
molecular breeding can increase agricultural production. Genomic prediction or
selection (GS) plays a complementary role to genome-wide association studies
(GWAS), which is the primary method to identify genes underlying phenotypes.
Unfortunately, most computing tools cannot perform data analyses for both GWAS
and GS. Furthermore, the majority of these tools are executed through a command
line interface (CLI), which requires programming skills. Non-programmers struggle
to use them efficiently because of the steep learning curves and zero tolerance
for data formats and mistakes when inputting keywords and parameters. To address
these problems, this study developed a software package, named the Intelligent
Prediction and Association Tool (iPat), with a user-friendly graphical user
interface. With iPat, GWAS or GS can be performed using a pointing device to
simply drag and/or click on graphical elements to specify input data files,
choose input parameters and select analytical models. Models available to users
include those implemented in third party CLI packages such as GAPIT, PLINK,
FarmCPU, BLINK, rrBLUP and BGLR. Users can choose any data format and conduct
analyses with any of these packages. File conversions are automatically conducted
for specified input data and selected packages. A GWAS-assisted genomic
prediction method was implemented to perform genomic prediction using any GWAS
method such as FarmCPU. iPat was written in Java for adaptation to multiple
operating systems including Windows, Mac and Linux. Availability and
implementation: The iPat executable file, user manual, tutorials and example
datasets are freely available at http://zzlab.net/iPat. Contact:
zhiwu.zhang@wsu.edu.
PMID- 29342242
TI - Meiotic spindle formation in mammalian oocytes: implications for human
infertility.
AB - In the final stage of oogenesis, mammalian oocytes generate a meiotic spindle and
undergo chromosome segregation to yield an egg that is ready for fertilization.
Herein, we describe the recent advances in understanding the mechanisms
controlling formation of the meiotic spindle in metaphase I (MI) and metaphase II
(MII) in mammalian oocytes, and focus on the differences between mouse and human
oocytes. Unlike mitotic cells, mammalian oocytes lack typical centrosomes that
consist of two centrioles and the surrounding pericentriolar matrix proteins,
which serve as microtubule-organizing centers (MTOCs) in most somatic cells.
Instead, oocytes rely on different mechanisms for the formation of microtubules
in MI spindles. Two different mechanisms have been described for MI spindle
formation in mammalian oocytes. Chromosome-mediated microtubule formation,
including RAN-mediated spindle formation and chromosomal passenger complex
mediated spindle elongation, controls the growth of microtubules from chromatin,
while acentriolar MTOC-mediated microtubule formation contributes to spindle
formation. Mouse oocytes utilize both chromatin- and MTOC-mediated pathways for
microtubule formation. The existence of both pathways may provide a fail-safe
mechanism to ensure high fidelity of chromosome segregation during meiosis.
Unlike mouse oocytes, human oocytes considered unsuitable for clinical in vitro
fertilization procedures, lack MTOCs; this may explain why meiosis in human
oocytes is often error-prone. Understanding the mechanisms of MI/MII spindle
formation, spindle assembly checkpoint, and chromosome segregation, in mammalian
oocytes, will provide valuable insights into the molecular mechanisms of human
infertility.
PMID- 29342243
TI - Devices in heart failure; diagnosis, detection and disease modification.
AB - Introduction/background: Implantable cardiac devices are widely used in chronic
heart failure (CHF) therapy. This review covers current CHF treatment with
electronic cardiac devices, areas of discussion and emerging technologies.
Sources of data: A comprehensive search of available literature resources
including Pubmed, MEDLINE and EMBASE was performed. National and international
guidelines were accessed. Areas of agreement: Excessive right ventricular pacing
is detrimental to cardiac function. Cardiac resynchronization therapy is
beneficial in specific individuals with CHF. Areas of controversy: Implantable
cardioverter defibrillators might not benefit all. Optimizing CRT delivery.
Remote monitoring seems not to be of benefit in CHF. Growing points: Device-based
optimization. Areas timely for developing research: Personalization of device
therapy. Focussing implantable cardioverter defibrillator therapy. What to do at
implantable cardioverter defibrillator box change?
PMID- 29342244
TI - Gli2 Rescues Delays in Brain Development Induced by Kif3a Dysfunction.
AB - The primary cilium in neural stem cells plays distinct roles in different stages
during cortical development. Ciliary dysfunctions in human (i.e., ciliopathy)
cause developmental defects in multiple organs, including brain developmental
delays, which lead to intellectual disabilities and cognitive deficits. However,
effective treatment to this devastating developmental disorder is still lacking.
Here, we first investigated the effects of ciliopathy on neural stem cells by
knocking down Kif3a, a kinesin II motor required for ciliogenesis, in the
neurogenic stage of cortical development by in utero electroporation of mouse
embryos. Brains electroporated with Kif3a shRNA showed defects in neuronal
migration and differentiation, delays in neural stem cell cycle progression, and
failures in interkinetic nuclear migration. Interestingly, introduction of Gli1
and Gli2 both can restore the cell cycle progression by elevating cyclin D1 in
neural stem cells. Remarkably, enforced Gli2 expression, but not Gli1, partially
restored the ability of Kif3a-knockdown neurons to differentiate and move from
the germinal ventricular zone to the cortical plate. Moreover, Cyclin D1
knockdown abolished Gli2's rescue effect. These findings suggest Gli2 may rescue
neural stem cell proliferation, differentiation and migration through Cyclin D1
pathway and may serve as a potential therapeutic target for human ciliopathy
syndromes through modulating the progression of neural stem cell cycle.
PMID- 29342245
TI - Structure-Function Relationships of Olfactory and Taste Receptors.
AB - The field of chemical senses has made major progress in understanding the
cellular mechanisms of olfaction and taste in the past 2 decades. However, the
molecular understanding of odor and taste recognition is still lagging far behind
and will require solving multiple structures of the relevant full-length
receptors in complex with native ligands to achieve this goal. However, the
development of multiple complimentary strategies for the structure determination
of G protein-coupled receptors (GPCRs) makes this goal realistic. The common
conundrum of how multi-specific receptors that recognize a large number of
different ligands results in a sensory perception in the brain will only be fully
understood by a combination of high-resolution receptor structures and functional
studies. This review discusses the first steps on this pathway, including
biochemical and physiological assays, forward genetics approaches, molecular
modeling, and the first steps towards the structural biology of olfactory and
taste receptors.
PMID- 29342246
TI - Associations of Quadriceps Torque Properties with Muscle Size, Attenuation, and
Intramuscular Adipose Tissue in Older Adults.
AB - Background: Atrophy and fatty infiltration of muscle with aging are associated
with fractures and falls, however, their direct associations with muscle function
are not well described. It was hypothesized that participants with lower
quadriceps muscle attenuation, area, and greater intramuscular adipose tissue
(IMAT) will exhibit slower rates of torque development (RTD) and lower peak knee
extension torques. Methods: Data from 4,842 participants (2,041 men, 2,801 women)
from the Age Gene/Environment Susceptibility Reykjavik Study (mean age 76 +/- 0.1
years) with complete thigh computed tomography and isometric knee testing.
Regression models were adjusted for health, behavior, and comorbidities. Muscle
attenuation was further adjusted for muscle area and IMAT; muscle area adjusted
for IMAT and attenuation; and IMAT adjusted for muscle area and attenuation.
Standardized betas (beta) indicate association effect sizes. Results: In the
fully-adjusted models, attenuation (men beta = 0.06, 95% CI: 0.01, 0.11; women
beta = 0.07, 95% CI: 0.03, 0.11) and muscle area (men beta = 0.13, 95% CI: 0.07,
0.19; women beta = 0.10, 95% CI: 0.06, 0.15) were associated with knee RTD.
Attenuation (men beta = 0.12, 95% CI: 0.08, 0.16; women beta = 0.12, 95% CI:
0.09, 0.16) and muscle area (men beta = 0.38, 95% CI: 0.33, 0.43; women beta =
0.33, 95% CI: 0.29, 0.37) were associated with peak torque. Conclusions: These
data suggest that muscle attenuation and area are independently associated with
RTD and peak torque; and that area and attenuation demonstrate similar
contributions to RTD.
PMID- 29342247
TI - PEATH: single-individual haplotyping by a probabilistic evolutionary algorithm
with toggling.
AB - Motivation: Single-individual haplotyping (SIH) is critical in genomic
association studies and genetic diseases analysis. However, most genomic analysis
studies do not perform haplotype-phasing analysis due to its complexity. Several
computational methods have been developed to solve the SIH problem, but these
approaches have not generated sufficiently reliable haplotypes. Results: Here, we
propose a novel SIH algorithm, called PEATH (Probabilistic Evolutionary Algorithm
with Toggling for Haplotyping), to achieve more accurate and reliable
haplotyping. The proposed PEATH method was compared to the most recent algorithms
in terms of the phased length, N50 length, switch error rate and minimum error
correction. The PEATH algorithm consistently provides the best phase and N50
lengths, as long as possible, given datasets. In addition, verification of the
simulation data demonstrated that the PEATH method outperforms other methods on
high noisy data. Additionally, the experimental results of a real dataset
confirmed that the PEATH method achieved comparable or better accuracy.
Availability and implementation: Source code of PEATH is available at
https://github.com/jcna99/PEATH. Contact: jkrhee@catholic.ac.kr or
sooyong.shin@gmail.com. Supplementary information: Supplementary data are
available at Bioinformatics online.
PMID- 29342248
TI - Clinical considerations of the role of palbociclib in the management of advanced
breast cancer patients with and without visceral metastases.
AB - Background: This report assesses the efficacy and safety of palbociclib plus
endocrine therapy (ET) in women with hormone receptor-positive, human epidermal
growth factor receptor 2-negative advanced breast cancer (ABC) with or without
visceral metastases. Patients and methods: Pre- and postmenopausal women with
disease progression following prior ET (PALOMA-3; N = 521) and postmenopausal
women untreated for ABC (PALOMA-2; N = 666) were randomized 2 : 1 to ET
(fulvestrant or letrozole, respectively) plus palbociclib or placebo. Progression
free survival (PFS), safety, and patient-reported quality of life (QoL) were
evaluated by prior treatment and visceral involvement. Results: Visceral
metastases incidence was higher in patients with prior resistance to ET (58.3%,
PALOMA-3) than in patients naive to ET in the ABC setting (48.6%, PALOMA-2). In
patients with prior resistance to ET and visceral metastases, median PFS (mPFS)
was 9.2 months with palbociclib plus fulvestrant versus 3.4 months with placebo
plus fulvestrant [hazard ratio (HR), 0.47; 95% confidence interval (CI), 0.35
0.61], and objective response rate (ORR) was 28.0% versus 6.7%, respectively. In
patients with nonvisceral metastases, mPFS was 16.6 versus 7.3 months, HR 0.53;
95% CI 0.36-0.77. In patients with visceral disease and naive to ET in the
advanced disease setting, mPFS was 19.3 months with palbociclib plus letrozole
versus 12.9 months with placebo plus letrozole (HR 0.63; 95% CI 0.47-0.85); ORR
was 55.1% versus 40.0%; in patients with nonvisceral disease, mPFS was not
reached with palbociclib plus letrozole versus 16.8 months with placebo plus
letrozole (HR 0.50; 95% CI 0.36-0.70). In patients with prior resistance to ET
with visceral metastases, palbociclib plus fulvestrant significantly delayed
deterioration of QoL versus placebo plus fulvestrant, whereas patient-reported
QoL was maintained with palbociclib plus letrozole in patients naive to endocrine
based therapy for ABC. Conclusions: Palbociclib plus ET prolonged mPFS in
patients with visceral metastases, increased ORRs, and in patients previously
treated for ABC, delayed QoL deterioration, presenting a standard treatment
option among patients with visceral metastases amenable to endocrine-based
therapy. Clinical trial registration: NCT01942135, NCT01740427.
PMID- 29342249
TI - Splice Expression Variation Analysis (SEVA) for inter-tumor heterogeneity of gene
isoform usage in cancer.
AB - Motivation: Current bioinformatics methods to detect changes in gene isoform
usage in distinct phenotypes compare the relative expected isoform usage in
phenotypes. These statistics model differences in isoform usage in normal
tissues, which have stable regulation of gene splicing. Pathological conditions,
such as cancer, can have broken regulation of splicing that increases the
heterogeneity of the expression of splice variants. Inferring events with such
differential heterogeneity in gene isoform usage requires new statistical
approaches. Results: We introduce Splice Expression Variability Analysis (SEVA)
to model increased heterogeneity of splice variant usage between conditions (e.g.
tumor and normal samples). SEVA uses a rank-based multivariate statistic that
compares the variability of junction expression profiles within one condition to
the variability within another. Simulated data show that SEVA is unique in
modeling heterogeneity of gene isoform usage, and benchmark SEVA's performance
against EBSeq, DiffSplice and rMATS that model differential isoform usage instead
of heterogeneity. We confirm the accuracy of SEVA in identifying known splice
variants in head and neck cancer and perform cross-study validation of novel
splice variants. A novel comparison of splice variant heterogeneity between
subtypes of head and neck cancer demonstrated unanticipated similarity between
the heterogeneity of gene isoform usage in HPV-positive and HPV-negative subtypes
and anticipated increased heterogeneity among HPV-negative samples with mutations
in genes that regulate the splice variant machinery. These results show that SEVA
accurately models differential heterogeneity of gene isoform usage from RNA-seq
data. Availability and implementation: SEVA is implemented in the R/Bioconductor
package GSReg. Contact: bahman@jhu.edu or favorov@sensi.org or ejfertig@jhmi.edu.
Supplementary information: Supplementary data are available at Bioinformatics
online.
PMID- 29342250
TI - Pneumococcal Community-Acquired Pneumonia Detected by Serotype-Specific Urinary
Antigen Detection Assays.
AB - Background: Streptococcus pneumoniae is considered the leading bacterial cause of
pneumonia in adults. Yet, it was not commonly detected by traditional culture
based and conventional urinary testing in a recent multicenter etiology study of
adults hospitalized with community-acquired pneumonia (CAP). We used novel
serotype-specific urinary antigen detection (SSUAD) assays to determine whether
pneumococcal cases were missed by traditional testing. Methods: We studied adult
patients hospitalized with CAP at 5 hospitals in Chicago and Nashville (2010
2012) and enrolled in the Etiology of Pneumonia in the Community (EPIC) study.
Traditional diagnostic testing included blood and sputum cultures and
conventional urine antigen detection (ie, BinaxNOW). We applied SSUAD assays that
target serotypes included in the 13-valent pneumococcal conjugate vaccine (PCV13)
to stored residual urine specimens. Results: Among 1736 patients with SSUAD and
>=1 traditional pneumococcal test performed, we identified 169 (9.7%) cases of
pneumococcal CAP. Traditional tests identified 93 (5.4%) and SSUAD identified 76
(4.4%) additional cases. Among 14 PCV13-serotype cases identified by culture,
SSUAD correctly identified the same serotype in all of them. Cases identified by
SSUAD vs traditional tests were similar in most demographic and clinical
characteristics, although disease severity and procalcitonin concentration were
highest among those with positive blood cultures. The proportion of PCV13
serotype cases identified was not significantly different between the first and
second July-June study periods (6.4% vs 4.0%). Conclusions: Although restricted
to the detection of only 13 serotypes, SSUAD testing substantially increased the
detection of pneumococcal pneumonia among adults hospitalized with CAP.
PMID- 29342252
TI - Triglyceride-rich lipoprotein cholesterol (TRL-C): the ugly stepsister of LDL-C.
PMID- 29342251
TI - Kinetics of Serological Responses in Critically Ill Patients Hospitalized With
2009 Pandemic Influenza A(H1N1) Virus Infection in Canada, 2009-2011.
AB - Background: The kinetics of the antibody response during severe influenza are not
well documented. Methods: Critically ill patients infected with 2009 pandemic
influenza A(H1N1) virus (A[H1N1]pdm09), confirmed by reverse-transcription
polymerase chain reaction analysis or seroconversion (defined as a >=4-fold rise
in titers), during 2009-2011 in Canada were prospectively studied. Antibody
titers in serially collected sera were determined using hemagglutinin inhibition
(HAI) and microneutralization assays. Average antibody curves were estimated
using linear mixed-effects models and compared by patient outcome, age, and
corticosteroid treatment. Results: Of 47 patients with A(H1N1)pdm09 virus
infection (median age, 47 years), 59% had baseline HAI titers of <40, and 68% had
baseline neutralizing titers of <40. Antibody titers rose quickly after symptom
onset, and, by day 14, 83% of patients had HAI titers of >=40, and 80% had
neutralizing titers >=40. Baseline HAI titers were significantly higher in
patients who died compared with patients who survived; however, the antibody
kinetics were similar by patient outcome and corticosteroid treatment. Geometric
mean titers over time in older patients were lower than those in younger
patients. Conclusions: Critically ill patients with influenza A(H1N1)pdm09 virus
infection had strong HAI and neutralizing antibody responses during their
illness. Antibody kinetics differed by age but were not associated with patient
outcome.
PMID- 29342253
TI - Comparison of EQ-5D and 15D instruments for assessing the health-related quality
of life in cardiac surgery patients.
AB - Aims: Patient-centred outcomes can be measured with different instruments. We
compared the performance of two health-related quality-of-life (HRQoL) measures,
EQ-5D and 15D, in patients undergoing elective coronary artery bypass grafting
(CABG). Methods and results: Patients who were admitted for elective CABG in
Kuopio University Hospital Finland in 2012-14 and had completed both instruments
concurrently as part of the admission process (n = 182). Follow-up was conducted
by postal survey 12 months after the CABG operation. The validity, agreement, and
responsiveness to change of both instruments were examined. The mean baseline
HRQoL index scores obtained by the EQ-5D and the 15D were 0.795 and 0.859,
respectively (P < 0.001 for difference). The agreement between instruments was
poor (Spearman's rho = 0.449; P < 0.001). Observed ceiling effects at baseline
for the EQ-5D and 15D were 31.9 and 4.4%, respectively. EQ-5D was able to
discriminate distinct Canadian Cardiovascular Society groups. During the 1-year
follow-up, clinically important improvement was observed in 39.6 and 53.3% of
patients with the EQ-5D and the 15D, respectively. However, with the 15D, the
number of operated patients required to produce one additional quality-adjusted
life year (QALY) was more than twice as high compared with the EQ-5D. Conclusion:
EQ-5D and 15D do not appear to be interchangeable when patient-centred outcomes
in CABG patients are assessed. The EQ-5D seems to have better discriminative
power and known-group validity, whereas the 15D is more sensitive to change over
time. These instruments lead to significantly different estimates concerning the
number of QALYs gained.
PMID- 29342255
TI - Thoracoscopic left atrial appendage clipping as novel treatment option for peri
device leakage.
PMID- 29342254
TI - Distinctive Desmoplastic 3D Morphology Associated With BRAFV600E in Papillary
Thyroid Cancers.
AB - Context: Although 60% of papillary thyroid carcinomas are BRAFV600E mutant
(PTCV600E), the increased aggressiveness of these cancers is still debated.
Objective: For PTCV600E we aimed to further characterize the extent of the stroma
and its activation, the three-dimensional (3D) tumor-stroma interface, and the
proliferation rates of tumor and stromal fibroblasts. Design: We analyzed exomes,
transcriptomes, and images of 364 papillary thyroid carcinoma (PTCs) from The
Cancer Genome Atlas (TCGA), including 211 PTCV600E; stained 22 independent PTCs
for BRAFV600E and Ki67; sequenced the exomes and stained BRAFV600E in 5 primary
tumor blocks and 4 nodal metastases from one patient with PTCV600E; and
reconstructed the 3D volumes of one tumor and one metastatic block at
histological resolution. Results: In TCGA, BRAFV600E was associated with higher
expression of proliferation markers and lower expression of thyroid
differentiation markers, independently of tumor purity. Moreover, PTCV600E, in
line with their overall lower purity, also had higher expression of fibroblast-
and T cell-associated genes and presented more fibrosis. Tumor cells that
appeared disconnected on two-dimensional histological slices were revealed to be
part of a unique tumor component in the 3D reconstructed microvolumes, and they
formed a surprisingly complex connected space, infiltrating a proliferative
stroma. Finally, in our PTC set, both stromal fibroblasts and tumor cells
presented higher proliferation rates in PTCV600E. Conclusions: Our results
support the increased aggressiveness associated with BRAFV600E in PTC and shed
light on the important role of the stroma in tumor expansion. The greater and
more active fibrotic component predicts better efficiency of combined targeted
treatments, as previously proposed for melanomaV600E.
PMID- 29342256
TI - Comparison of pregnancy outcomes between maternity waiting home users and non
users at hospitals with and without a maternity waiting home: retrospective
cohort study.
AB - Objective: To examine the impact of a maternity waiting home (MWH) by comparing
pregnancy outcomes between users and non-users at hospitals with and without an
MWH. Methods: We conducted a retrospective cohort study in Ethiopia comparing one
hospital with an MWH (Attat) to a second hospital without one (Butajira). A
structured questionnaire among sampled women in 2014 and hospital records from
2011 to 2014 were used to compare sociodemographic characteristics and pregnancy
outcomes between Attat MWH users and non-MWH users, Attat MWH users and Butajira,
and Attat non-MWH users and Butajira. chi2 or ORs with 95% CIs were calculated.
Results: Compared with Attat non-MWH users (n=306) and Butajira women (n=153),
Attat MWH users (n=244) were more often multiparous (multipara vs primigravida:
OR 4.43 [95% CI 2.94 to 6.68] and OR 3.58 [95% CI 2.24 to 5.73]), less educated
(no schooling vs secondary school: OR 2.62 [95% CI 1.53 to 4.46] and OR 5.21 [95%
CI 2.83 to 9.61], primary vs secondary school: OR 4.84 [95% CI 2.84 to 8.25] and
OR 5.19 [95% CI 2.91 to 9.27]), poor (poor vs wealthy: OR 8.94 [95% CI 5.13 to
15.61] and OR 12.34 [95% CI 6.78 to 22.44] and further from the hospital (2 h 27
min vs 1 h 00 min and 1 h 12 min: OR 3.08 [95% CI 2.50 to 3.80] and OR 2.18 [95%
CI 1.78 to 2.67]). Comparing hospital records of Attat MWH users (n=2784) with
Attat non-users (n=5423) and Butajira women (n=9472), maternal deaths were 0 vs
20 (0.4%; p=0.001) and 31 (0.3%; p=0.003), stillbirths 38 (1.4%) vs 393 (7.2%)
(OR 0.18 [95% CI 0.13 to 0.25]) and 717 (7.6%) (OR 0.17 [95% CI 0.12 to 0.24])
and uterine ruptures 2 (0.1%) vs 40 (1.1%) (OR 0.05 [95% CI 0.01 to 0.19]) and
122 (1.8%) (OR 0.04 (95% CI 0.01 to 0.16]). No significant differences were found
regarding maternal deaths and stillbirths between Attat non-users and Butajira
women. Conclusions: Attat MWH users had less favourable sociodemographic
characteristics but better birth outcomes than Attat non-users and Butajira
women.
PMID- 29342257
TI - Trajectories of alcohol consumption prior to the diagnosis of type 2 diabetes: a
longitudinal case-cohort study.
AB - Background: Non-linear associations have been reported between baseline measures
of alcohol consumption and type 2 diabetes (T2DM). However, given that drinking
varies over the adult life course, we investigated whether differences existed in
the longitudinal trajectory of alcohol consumption according to T2DM status.
Methods: For a case-cohort (916 incident cases; 7376 controls) of British civil
servants nested within the Whitehall II cohort, the self-reported weekly volume
of alcohol consumption was traced backwards from the date of diagnosis or
censoring to the beginning of the study, covering a period of up to 28 years.
Mean trajectories of alcohol intake were estimated separately by diagnosis status
using random-effects models. Results: Drinking increased linearly among male
cases before diagnosis, but declined among male non-cases prior to censoring. At
the time of diagnosis or censoring, consumption among those who developed T2DM
was 33.4 g/week greater on average. These patterns were not apparent among women.
Here, alcohol intake among female cases was consistently below that of non-cases,
with the difference in consumption most pronounced around 15 years prior to
diagnosis or censoring, at ~28.0 g/week. Disparities by diagnosis status were
attenuated following adjustment for potential confounders, including the
frequency of consumption and metabolic factors. Drinking among male and female
cases declined following diagnosis. Conclusions: Differences in the weekly volume
of alcohol consumption are reported in the years leading up to diagnosis or
censoring. Although male and female cases predominantly consumed alcohol at
volumes lower than or equal to those who were not diagnosed, these disparities
appear to be largely explained by a range of socio-demographic and lifestyle
factors. Where disparities are observed between cases and non-cases, adjusted
absolute differences are small in magnitude. The decision to drink alcohol should
not be motivated by a perceived benefit to T2DM risk.
PMID- 29342258
TI - Insulin and Estrogen Independently and Differentially Reduce Macronutrient Intake
in Healthy Men.
AB - Context: Insulin administration to the central nervous system inhibits food
intake, but this effect has been found to be less pronounced in female compared
with male organisms. This sex-specific pattern has been suggested to arise from a
modulating influence of estrogen signaling on the insulin effect. Objective: We
assessed in healthy young men whether pretreatment with transdermal estradiol
interacts with the hypophagic effect of central nervous insulin administration
via the intranasal pathway. Design, Setting, Participants, and Intervention:
According to a 2*2 design, two groups of men (n = 16 in each group) received a 3
day transdermal estradiol (100 ug/24 h) or placebo pretreatment and on two
separate mornings were intranasally administered 160 IU regular human insulin or
placebo. Main Outcome Measures: We assessed free-choice ad libitum calorie intake
from a rich breakfast buffet and relevant blood parameters in samples collected
before and after breakfast. Results: Estrogen treatment induced a 3.5-fold
increase in serum estradiol concentrations and suppressed serum testosterone
concentrations by 70%. Independent of estradiol administration, intranasal
insulin reduced the intake of carbohydrates during breakfast, attenuating in
particular the consumption of sweet, palatable foods. Estradiol treatment per se
decreased protein consumption. We did not find indicators of eating-related
interactions between both hormones. Conclusions: Results indicate that, in an
acute setting, estrogen does not interact with central nervous insulin signaling
in the control of eating behavior in healthy men. Insulin and estradiol rather
exert independent inhibiting effects on macronutrient intake.
PMID- 29342259
TI - False starts in 'test and start': a qualitative study of reasons for delayed
antiretroviral therapy in Swaziland.
AB - Background: Test and start, antiretroviral therapy (ART) for all HIV-positive
individuals, is a WHO-recommended treatment guideline. In Swaziland, test and
start has been evaluated through the MaxART implementation study. This article
examines why, in MaxART, some newly diagnosed HIV-positive clients delayed
initiating ART. Methods: Thirteen HIV-positive clients who delayed ART for >=90 d
after testing were identified from the MaxART study database and interviewed.
Interviews were audio recorded, transcribed and translated into English for
qualitative content analysis. Results: Respondents had often tested positive
several times before initiating ART, with the initial diagnosis sometimes
completely unexpected. Repeat testing-and delayed ART-was linked to a desire to
come to terms with their diagnosis and prepare for a lifelong treatment course.
Clients previously enrolled in pre-ART, particularly with high CD4 counts, had
internalized past messages about ART as being non-essential and taking care of
oneself through other means. Concerns about ART-related adverse events were
weighed against these messages. Worries about inadvertent disclosure and its
impact on social and economic relationships also discouraged initiation.
Conclusion: Although potentially reducing logistical barriers, expedited ART
initiation does not necessarily accommodate some clients' need for time to come
to terms with the diagnosis and the prospect of lifelong treatment.
PMID- 29342260
TI - Interaction between Staphylococcus aureus and Pseudomonas aeruginosa is
beneficial for colonisation and pathogenicity in a mixed biofilm.
AB - Debate regarding the co-existence of Staphylococcus aureus and Pseudomonas
aeruginosa in wounds remains contentious, with the dominant hypothesis describing
a situation akin to niche partitioning, whereby both microorganisms are present
but occupy distinct regions of the wound without interacting. In contrast, we
hypothesised that these microorganisms do interact during early co-colonisation
in a manner beneficial to both bacteria. We assessed competitive interaction
between S. aureus and P. aeruginosa in biofilm cultured for 24-72 h and bacterial
aggregates analogous to those observed in early (<24 h) biofilm formation, and
interaction with human keratinocytes. We observed that S. aureus predominated in
biofilm and non-attached bacterial aggregates, acting as a pioneer for the
attachment of P. aeruginosa. We report for the first time that S. aureus mediates
a significant (P < 0.05) increase in the attachment of P. aeruginosa to human
keratinocytes, and that P. aeruginosa promotes an invasive phenotype in S.
aureus. We show that co-infected keratinocytes exhibit an intermediate
inflammatory response concurrent with impaired wound closure that is in keeping
with a sustained proinflammatory response which allows for persistent microbial
colonisation. These studies demonstrate that, contrary to the dominant
hypothesis, interactions between S. aureus and P. aeruginosa may be an important
factor for both colonisation and pathogenicity in the chronic infected wound.
PMID- 29342261
TI - Prevalence of smoking during pregnancy and associated risk factors: a cross
sectional study in Northern Greece.
AB - Background: Many pregnant women smoke despite the extensive data available on the
detrimental perinatal outcomes. The aim of this study was to estimate the
prevalence of smoking during pregnancy and to identify the factors associated
with smoking among pregnant women in Northern Greece. Methods: A sample of
pregnant women (mean gestational age: 12.6 weeks) participated in a cross
sectional study assessing the prevalence of smoking. Univariate and multivariate
logistic regression analyses were used to examine the factors associated with
their smoking behavior. Results: A total of 3688 pregnant women (mean age: 31.1
+/- 5.0 years) completed the survey. On the basis of their answers, 36.1% (n =
1330) were smokers before pregnancy and 13.2% (n = 487) were still smoking at the
end of the first trimester. Eight hundred and forty-three women (63.4%) gave up
smoking, apparently motivated by their pregnancy. A multivariate analysis showed
an independent positive association of nulliparity, Greek ethnicity, age >35
years and a BMI > 30 with smoking before pregnancy. Smoking during pregnancy was
more common among naturally conceived pregnancies and women with a BMI >
30.Cessation rates were lower for naturally conceived pregnancies, immigrants and
multiparous women. Conclusion: About one third of women who smoked before
pregnancy continued to smoke during pregnancy. Naturally conceiving, multiparous
and immigrant women are less likely to quit smoking when pregnant. Tailored
smoking cessation interventions should target women early in their pregnancy.
PMID- 29342262
TI - Preliminary study of 1940 nm thulium laser usage in peroral endoscopic myotomy
for achalasia.
AB - Esophageal achalasia is a type of motility disorder characterized by incomplete
relaxation of lower esophageal sphincter (LES) and absence of esophageal
peristalsis. Peroral endoscopic myotomy (POEM) is a new treatment option for
achalasia that is less invasive, more effective, and safe as compared to surgery.
High-frequency electrotome is commonly used in POEM, but takes longer time to
make the tunnel in the esophagus and causes many complications. The thulium laser
decreases the risk of bleeding and perforation in endoscopy but has not been
reported in digestive diseases, especially in POEM. Therefore, the aim of this
study is to evaluate the feasibility of the 1940 nm thulium laser in POEM. From
March 2015 to August 2015, five patients with achalasia at the Digestive
department, Beijing Friendship Hospital, Capital Medical University, Beijing,
China were included. Before the procedure, the patients' gender, age, and
duration of symptoms were recorded. Eckardt symptom score and LES thickness,
which measured by endoscopic ultrasonography, were recorded. While the subtypes
of achalasia (according to the Chicago classification), lower esophagus sphincter
resting pressure (LESRP) and integrated relaxation pressure (IRP) were measured
by HRM for all patients. Barium esophagram was also used to rule out anatomical
lesions, esophageal varices, or neoplasia, which may cause similar symptoms. All
examinations were performed one week before POEM. POEM was performed with the
1940 nm thulium laser under general anesthesia. Eckardt score, procedure
duration, myotomy length, and complications were recorded one week after POEM.
All the patients were followed-up at two weeks and four weeks after POEM. POEM
was successfully performed in all five patients. The mean age of the patients was
38.8 years (24-54 years). Achalasia subtypes were type I (n = 1), II (n = 2), and
III (n = 2). The operation duration was 186, 180, 111, 75, and 126 minutes for
the five cases. Pre/postprocedure Eckardt scores were 3/0, 7/0, 5/1, 6/0, and
9/0. Pre/postprocedure LESRP (mmHg) were 45.3/26.4, 18.0/1.1, 25.8/10.4,
16.5/11.2, and 24.2/20.8. Pre/postprocedure IRP (mmHg) were 27.3/15.5, 15.4/4.2,
5.7/6.8, 15.5/10.1, and 13.1/14, respectively. No adverse events occurred during
the procedure. After POEM, subcutaneous emphysema occurred in case 1 on the first
day, which relieved spontaneously after two days without special intervention.
Infection occurred in case 5 on the day of POEM was healed with antibiotics three
days later. The 1940 nm thulium laser is feasible for POEM procedure. Further
studies are needed to determine whether the 1940 nm thulium laser is better than
high-frequency electrotome.
PMID- 29342263
TI - Sri Lanka's post-tsunami health system recovery: a qualitative analysis of
physician perspectives.
AB - Background: The 2004 Indian Ocean tsunami caused significant damage to the health
system in Sri Lanka. Rebuilding infrastructure and improving the mental health
system were targets of recovery policies. Retrospective analyses of the post
tsunami health system recovery in Sri Lanka lack the perspectives of local
stakeholders, including health care providers. Methods: In 2014 we interviewed 23
Sri Lankan physicians from the Eastern and Southern regions. Participants were
recruited with snowball sampling. We used a content analysis approach in
analysing the transcriptions. Results: Sri Lankan physicians critiqued
governance, sustainability and equity in the health system recovery. They held
leadership roles as facilitators and sustainers of specific projects but were
rarely formally consulted in recovery strategic planning. They identified
instances of poor coordination among partners, corruption trends, local resource
mismatches, regional resource disparities and the influence of the Sri Lankan
civil war. Conclusions: Post-tsunami health system recovery planning and
implementation in Sri Lanka did not involve local physician stakeholders in ways
that have been prioritized more recently in other recovery frameworks. Despite
limited formal inclusion, local physicians developed significant leadership roles
that have informed their critical perspectives on the health system recovery.
PMID- 29342265
TI - Oesophageal duplication cyst mimicking cardiac mass.
PMID- 29342264
TI - Effect of Continuous Glucose Monitoring on Glycemic Control, Acute Admissions,
and Quality of Life: A Real-World Study.
AB - Context: Randomized controlled trials evaluating real-time continuous glucose
monitoring (RT-CGM) patients with type 1 diabetes (T1D) show improved glycemic
control, but limited data are available on real-world use. Objective: To assess
impact of RT-CGM in real-world settings on glycemic control, hospital admissions,
work absenteeism, and quality of life (QOL). Design: Prospective, observational,
multicenter, cohort study. Participants: A total of 515 adults with T1D on
continuous subcutaneous insulin infusion (CSII) therapy starting in the Belgian
RT-CGM reimbursement program. Intervention: Initiation of RT-CGM reimbursement.
Main Outcome Measure: Hemoglobin A1c (HbA1c) evolution from baseline to 12
months. Results: Between September 1, 2014, and December 31, 2016, 515 adults
entered the reimbursement system. Over this period, 417 (81%) patients used RT
CGM for at least 12 months. Baseline HbA1c was 7.7 +/- 0.9% (61 +/- 9.8 mmol/mol)
and decreased to 7.4 +/- 0.8% (57 +/- 8.7 mmol/mol) at 12 months (P < 0.0001).
Subjects who started RT-CGM because of insufficient glycemic control showed
stronger decrease in HbA1c at 4, 8, and 12 months compared with patients who
started because of hypoglycemia or pregnancy. In the year preceding
reimbursement, 16% of patients were hospitalized for severe hypoglycemia or
ketoacidosis in contrast to 4% (P < 0.0005) the following year, with decrease in
admission days from 54 to 18 per 100 patient years (P < 0.0005). In the same
period, work absenteeism decreased and QOL improved significantly, with strong
decline in fear of hypoglycemia. Conclusion: Sensor-augmented pump therapy in
patients with T1D followed in specialized centers improves HbA1c, fear of
hypoglycemia, and QOL, whereas work absenteeism and admissions for acute diabetes
complications decreased.
PMID- 29342267
TI - Safety of Single-Dose Primaquine in G6PD-Deficient and G6PD-Normal Males in Mali
Without Malaria: An Open-Label, Phase 1, Dose-Adjustment Trial.
AB - Background: The World Health Organization recommendation on the use of a single
low dose of primaquine (SLD-PQ) to reduce Plasmodium falciparum malaria
transmission requires more safety data. Methods: We conducted an open-label,
nonrandomized, dose-adjustment trial of the safety of 3 single doses of
primaquine in glucose-6-phosphate dehydrogenase (G6PD)-deficient adult males in
Mali, followed by an assessment of safety in G6PD-deficient boys aged 11-17 years
and those aged 5-10 years, including G6PD-normal control groups. The primary
outcome was the greatest within-person percentage drop in hemoglobin
concentration within 10 days after treatment. Results: Fifty-one participants
were included in analysis. G6PD-deficient adult males received 0.40, 0.45, or
0.50 mg/kg of SLD-PQ. G6PD-deficient boys received 0.40 mg/kg of SLD-PQ. There
was no evidence of symptomatic hemolysis, and adverse events considered related
to study drug (n = 4) were mild. The mean largest within-person percentage change
in hemoglobin level between days 0 and 10 was -9.7% (95% confidence interval
[CI], -13.5% to -5.90%) in G6PD-deficient adults receiving 0.50 mg/kg of SLD-PQ,
11.5% (95% CI, -16.1% to -6.96%) in G6PD-deficient boys aged 11-17 years, and
9.61% (95% CI, -7.59% to -13.9%) in G6PD-deficient boys aged 5-10 years. The
lowest hemoglobin concentration at any point during the study was 92 g/L.
Conclusion: SLD-PQ doses between 0.40 and 0.50 mg/kg were well tolerated in G6PD
deficient males in Mali. Clinical Trials Registration: NCT02535767.
PMID- 29342266
TI - Causes, Patterns, and Severity of Androgen Excess in 1205 Consecutively Recruited
Women.
AB - Context: Androgen excess in women is predominantly due to underlying polycystic
ovary syndrome (PCOS). However, there is a lack of clarity regarding patterns and
severity of androgen excess that should be considered predictive of non-PCOS
pathology. Objective: We examined the diagnostic utility of simultaneous
measurement of serum dehydroepiandrosterone sulfate (DHEAS), androstenedione
(A4), and testosterone (T) to delineate biochemical signatures and cutoffs
predictive of non-PCOS disorders in women with androgen excess. Design:
Retrospective review of all women undergoing serum androgen measurement at a
large tertiary referral center between 2012 and 2016. Serum A4 and T were
measured by tandem mass spectrometry and DHEAS by immunoassay. Patients with at
least one increased serum androgen underwent phenotyping by clinical notes
review. Results: In 1205 women, DHEAS, A4, and T were measured simultaneously.
PCOS was the most common diagnosis in premenopausal (89%) and postmenopausal
women (29%). A4 was increased in all adrenocortical carcinoma (ACC) cases (n =
15) and T in all ovarian hyperthecosis (OHT) cases (n = 7); all but one case of
congenital adrenal hyperplasia (CAH; n = 18) were identified by increased levels
of A4 and/or T. In premenopausal women, CAH was a prevalent cause of severe A4
(59%) and T (43%) excess; severe DHEAS excess was predominantly due to PCOS
(80%). In postmenopausal women, all cases of severe DHEAS and A4 excess were
caused by ACC and severe T excess equally by ACC and OHT. Conclusions: Pattern
and severity of androgen excess are important predictors of non-PCOS pathology
and may be used to guide further investigations as appropriate.
PMID- 29342268
TI - Reduced Expression of Mismatch Repair Genes MSH6/MSH2 Directly Promotes Pituitary
Tumor Growth via the ATR-Chk1 Pathway.
AB - Context: The mechanisms of pituitary adenoma (PA) pathogenesis and proliferation
remain largely unknown. Objectives: To clarify the role of mismatch repair (MMR)
genes in the molecular mechanism of PA proliferation. Design: We performed
quantitative analyses by real-time polymerase chain reaction and
immunohistochemistry to detect MMR gene and protein expression in human PAs (n =
47). We also performed correlation analyses of expression levels and tumor volume
doubling time (TVDT; n = 31). Specifically, correlation analyses were performed
between genes with significant correlation and ataxiatelangiectasia and Rad3
related (ATR) expression in cell-cycle regulatory mechanism ATR-checkpoint kinase
1 (Chk1) pathway (n = 93). We investigated the effect of reduced gene expression
on cell proliferation and ATR gene expression in AtT-20ins cells and primary
cultures of human PAs. Results: Expression of mutS homologs 6 and 2 (MSH6 and
MSH2) was positively associated with TVDT (R = 0.52, P = 0.003, and R = 0.44, P =
0.01), as were the corresponding protein levels. Gene expression was positively
associated with ATR expression (R = 0.47, P < 0.00001, and R = 0.49, P <
0.00001). In AtT-20ins, the reduction of MSH6 and/or MSH2 expression by small
interfering RNA significantly promoted cell proliferation by decreasing ATR
expression. This effect was also observed in primary culture. Conclusion:
Reduction of MSH6 and MSH2 expression at the messenger RNA and protein levels
could be involved in direct PA proliferation by promoting cell-cycle progression
or decreasing the rate of apoptosis through interference with the function of the
ATR-Chk1 pathway.
PMID- 29342269
TI - A Silent Epidemic: The Prevalence, Incidence and Persistence of Mycoplasma
genitalium Among Young, Asymptomatic High-Risk Women in the United States.
AB - Background: Mycoplasma genitalium can result in pelvic inflammatory disease and
adverse pregnancy outcomes. We analyzed data collected from a prospective study
of asymptomatic bacterial vaginosis (BV) to determine the natural history of M.
genitalium. Methods: Women aged 15-25 years, with asymptomatic BV and >=2 risk
factors for sexually transmitted infection were recruited from 10 sites
throughout the United States. Vaginal swab samples were collected at enrollment
and through home-based testing every 2 months over 12 months. M. genitalium
nucleic acid amplification testing was performed for M. genitalium using
transcription-mediated assays (Hologic). The prevalence, incidence, and
persistence of M. genitalium, defined as all positive specimens during follow-up,
were estimated with 95% confidence intervals (CIs). Adjusted odds ratios (AOR)
were calculated using logistic and Poisson regression to evaluate participant
characteristics associated with M. genitalium infection. Results: Among 1139
women, 233 were M. genitalium positive, for a prevalence of 20.5% (95% CI, 18.2%
22.9%); 42 of 204 had persistent M. genitalium (20.6%). Among 801 M. genitalium
negative women at baseline, the M. genitalium incidence was 36.6 per 100 person
years (95% CI, 32.4-41.3). Black race (AOR, 1.92; 95% CI, 1.09-3.38), age <=21
years (1.40; 1.03-1.91), and prior pregnancy (1.36; 1.00-1.85) were associated
with prevalent M. genitalium; only black race was associated with incident M.
genitalium (P = .03). Conclusions: We identified high rates of prevalent,
incident, and persistent M. genitalium infections among young, high-risk women
with asymptomatic BV, supporting the need for clinical trials to evaluate the
impact of M. genitalium screening on female reproductive health outcomes.
PMID- 29342270
TI - Whole-genome analysis reveals the evolution and transmission of an MDR
DH/NAP11/106 Clostridium difficile clone in a paediatric hospital.
AB - Background: Clostridium difficile strain DH/NAP11/106, a relatively antibiotic
susceptible strain, is now the most common cause of C. difficile infection (CDI)
among adults in the USA. Objectives: To identify mechanisms underlying the
evolution and transmission of an MDR DH/NAP11/106 clone. Methods: WGS (Illumina
MiSeq), restriction endonuclease analysis (REA) and antibiotic susceptibility
testing were performed on 134 C. difficile isolates collected from paediatric
patients with CDI over a 2 year period. Results: Thirty-one of 134 (23%) isolates
were REA group DH. Pairwise single-nucleotide variant (SNV) analyses identified a
DH clone causing seven instances of CDI in two patients. During the 337 days
between the first and second CDI, Patient 1 (P1) received 313 days of antibiotic
therapy. Clindamycin and rifaximin resistance, and reduced vancomycin
susceptibility (MIC 0.5-2 mg/L), were newly identified in the relapsed isolate.
This MDR clone was transmitted to Patient 2 (P2) while P1 and P2 received care in
adjacent private rooms. P1 and P2 each developed two additional CDI relapses.
Comparative genomics analyses demonstrated SNVs in multiple antibiotic resistance
genes, including rpoB (rifaximin resistance), gyrB and a gene encoding PBP; gyrB
and PBP mutations did not consistently confer a resistance phenotype. The clone
also acquired a 46 000 bp genomic element, likely a conjugative plasmid, which
contained ermB (clindamycin resistance). The element shared 99% identity with the
genomic sequence of Faecalibacterium prausnitzii, an enteric commensal.
Conclusions: These data highlight the emergence of MDR in C. difficile strain
DH/NAP11/106 through multiple independent mechanisms probably as a consequence of
profound antibiotic pressure.
PMID- 29342271
TI - MELODI: Mining Enriched Literature Objects to Derive Intermediates.
AB - Background: The scientific literature contains a wealth of information from
different fields on potential disease mechanisms. However, identifying and
prioritizing mechanisms for further analytical evaluation presents enormous
challenges in terms of the quantity and diversity of published research. The
application of data mining approaches to the literature offers the potential to
identify and prioritize mechanisms for more focused and detailed analysis.
Methods: Here we present MELODI, a literature mining platform that can identify
mechanistic pathways between any two biomedical concepts. Results: Two case
studies demonstrate the potential uses of MELODI and how it can generate
hypotheses for further investigation. First, an analysis of ETS-related gene ERG
and prostate cancer derives the intermediate transcription factor SP1, recently
confirmed to be physically interacting with ERG. Second, examining the
relationship between a new potential risk factor for pancreatic cancer identifies
possible mechanistic insights which can be studied in vitro. Conclusions: We have
demonstrated the possible applications of MELODI, including two case studies.
MELODI has been implemented as a Python/Django web application, and is freely
available to use at [www.melodi.biocompute.org.uk].
PMID- 29342272
TI - Daily decision-making about food during pregnancy: a New Zealand study.
AB - Pregnancy has always been a life-changing event for women and their families, but
societal concern about pregnancy and motherhood has become intense in the digital
age. The role of health promotion agencies and others supplying health-related
resources about lifestyle behaviours is both important and in need of scrutiny.
Ever increasing advice for pregnant women, their families and health
professionals, abounds. This study of decision making during pregnancy
investigated how women made everyday decisions during pregnancy about food and
drink, as well as dietary supplements and medications, alcohol and recreational
drugs. This qualitative interview study was a side-arm to a double-blind
randomized, placebo-controlled trial conducted with pregnant women in Wellington
New Zealand, 2013-2016. Data from interviews with 20 women were analysed using
inductive thematic analysis. In relation to decision-making about lifestyle
behaviours, five themes emerged-Information about food; Wanted and unwanted
advice; Worry, anxiety and indecision; Making daily decisions about food; Changes
in decision making over time. Participating women talked more about food
selection and restriction advice than any other lifestyle topic. Analysis
demonstrated concern about information accuracy and overload from multiple,
diverse sources. Women described learning how to assess resource credibility, how
to develop decision-making skills, and who to trust. The study raises important
questions about how the health information environment, despite best intentions,
can be confusing or potentially harmful. The study underlines the continued
importance of the role health professionals have in not only interpreting
information to discuss individualized advice, but also in empowering pregnant
women to develop lifestyle-related decision-making skills.
PMID- 29342273
TI - Hypermethylation of EIF4E promoter is associated with early onset of gastric
cancer.
AB - Although gastric cancer (GC) in young adults (<= 45 years) accounts for fewer
than 10% of newly diagnosed cases, the young patients are more likely to have
advanced disease at presentation compared with elderly patients. Previous studies
have identified that the DNA methylation of genomes are different during aging.
Our study aimed to explore the association between DNA methylation and the onset
of GC. We applied Illumina HumanMethylation450 BeadChip to examine methylation
expression profiles and compared methylation expression patterns in five early
onset GC patients and seven elderly patients. Additionally, we evaluated the
associations of methylation expression with different clinicopathological
characteristics of GC. Our results showed that the pattern of genome-wide
methylation expression was significantly different between early onset and
elderly GC. The top 10 hypomethylation and hypermethylation CpG sites were
selected for further analyses in The Cancer Genome Atlas (TCGA) database. We
found that the hypermethylation of cg11037477, located at the promoter of EIF4E,
was significantly associated with age at diagnosis and the expression of EIF4E.
Besides, GC patients with high level of cg11037477 were more likely to have
advance disease with T3/T4 invasion and III/IV stage. The cg11037477
hypermethylation and EIF4E down-expression were significantly related to poor
survival of GC patients. Our study provides new insights into the molecular
mechanism of early onset patients with GC and suggests that methylation of
cg11037477 and expression of EIF4E may act as prognostic markers in GC.
PMID- 29342274
TI - Editorial.
PMID- 29342276
TI - A Predictive, Quantitative Model of Spiking Activity and Stimulus-Secretion
Coupling in Oxytocin Neurons.
AB - Oxytocin neurons of the rat hypothalamus project to the posterior pituitary,
where they secrete their products into the bloodstream. The pattern and quantity
of that release depends on the afferent inputs to the neurons, on their intrinsic
membrane properties, and on nonlinear interactions between spiking activity and
exocytosis: A given number of spikes will trigger more secretion when they arrive
close together. Here we present a quantitative computational model of oxytocin
neurons that can replicate the results of a wide variety of published
experiments. The spiking model mimics electrophysiological data of oxytocin cells
responding to cholecystokinin (CCK), a peptide produced in the gut after food
intake. The secretion model matches results from in vitro experiments on stimulus
secretion coupling in the posterior pituitary. We mimic the plasma clearance of
oxytocin with a two-compartment model, replicating the dynamics observed
experimentally after infusion and injection of oxytocin. Combining these models
allows us to infer, from measurements of oxytocin in plasma, the spiking activity
of the oxytocin neurons that produced that secretion. We have tested these
inferences with experimental data on oxytocin secretion and spiking activity in
response to intravenous injections of CCK. We show how intrinsic mechanisms of
the oxytocin neurons determine this relationship: In particular, we show that the
presence of an afterhyperpolarization (AHP) in oxytocin neurons dramatically
reduces the variability of their spiking activity and even more markedly reduces
the variability of oxytocin secretion. The AHP thus acts as a filter, protecting
the final product of oxytocin cells from noisy fluctuations.
PMID- 29342275
TI - Hot-spot KIF5A mutations cause familial ALS.
AB - Heterozygous missense mutations in the N-terminal motor or coiled-coil domains of
the kinesin family member 5A (KIF5A) gene cause monogenic spastic paraplegia
(HSP10) and Charcot-Marie-Tooth disease type 2 (CMT2). Moreover, heterozygous de
novo frame-shift mutations in the C-terminal domain of KIF5A are associated with
neonatal intractable myoclonus, a neurodevelopmental syndrome. These findings,
together with the observation that many of the disease genes associated with
amyotrophic lateral sclerosis disrupt cytoskeletal function and intracellular
transport, led us to hypothesize that mutations in KIF5A are also a cause of
amyotrophic lateral sclerosis. Using whole exome sequencing followed by rare
variant analysis of 426 patients with familial amyotrophic lateral sclerosis and
6137 control subjects, we detected an enrichment of KIF5A splice-site mutations
in amyotrophic lateral sclerosis (2/426 compared to 0/6137 in controls; P = 4.2 *
10-3), both located in a hot-spot in the C-terminus of the protein and predicted
to affect splicing exon 27. We additionally show co-segregation with amyotrophic
lateral sclerosis of two canonical splice-site mutations in two families.
Investigation of lymphoblast cell lines from patients with KIF5A splice-site
mutations revealed the loss of mutant RNA expression and suggested
haploinsufficiency as the most probable underlying molecular mechanism.
Furthermore, mRNA sequencing of a rare non-synonymous missense mutation
(predicting p.Arg1007Gly) located in the C-terminus of the protein shortly
upstream of the splice donor of exon 27 revealed defective KIF5A pre-mRNA
splicing in respective patient-derived cell lines owing to abrogation of the
donor site. Finally, the non-synonymous single nucleotide variant rs113247976
(minor allele frequency = 1.00% in controls, n = 6137), also located in the C
terminal region [p.(Pro986Leu) in exon 26], was significantly enriched in
familial amyotrophic lateral sclerosis patients (minor allele frequency = 3.40%;
P = 1.28 * 10-7). Our study demonstrates that mutations located specifically in a
C-terminal hotspot of KIF5A can cause a classical amyotrophic lateral sclerosis
phenotype, and underline the involvement of intracellular transport processes in
amyotrophic lateral sclerosis pathogenesis.
PMID- 29342277
TI - Finding Nemo: hybrid assembly with Oxford Nanopore and Illumina reads greatly
improves the clownfish (Amphiprion ocellaris) genome assembly.
AB - Background: Some of the most widely recognized coral reef fishes are clownfish or
anemonefish, members of the family Pomacentridae (subfamily: Amphiprioninae).
They are popular aquarium species due to their bright colours, adaptability to
captivity, and fascinating behavior. Their breeding biology (sequential
hermaphrodites) and symbiotic mutualism with sea anemones have attracted much
scientific interest. Moreover, there are some curious geographic-based phenotypes
that warrant investigation. Leveraging on the advancement in Nanopore long read
technology, we report the first hybrid assembly of the clown anemonefish
(Amphiprion ocellaris) genome utilizing Illumina and Nanopore reads, further
demonstrating the substantial impact of modest long read sequencing data sets on
improving genome assembly statistics. Results: We generated 43 Gb of short
Illumina reads and 9 Gb of long Nanopore reads, representing approximate genome
coverage of 54* and 11*, respectively, based on the range of estimated k-mer
predicted genome sizes of between 791 and 967 Mbp. The final assembled genome is
contained in 6404 scaffolds with an accumulated length of 880 Mb (96.3% BUSCO
calculated genome completeness). Compared with the Illumina-only assembly, the
hybrid approach generated 94% fewer scaffolds with an 18-fold increase in N50
length (401 kb) and increased the genome completeness by an additional 16%. A
total of 27 240 high-quality protein-coding genes were predicted from the clown
anemonefish, 26 211 (96%) of which were annotated functionally with information
from either sequence homology or protein signature searches. Conclusions: We
present the first genome of any anemonefish and demonstrate the value of low
coverage (~11*) long Nanopore read sequencing in improving both genome assembly
contiguity and completeness. The near-complete assembly of the A. ocellaris
genome will be an invaluable molecular resource for supporting a range of
genetic, genomic, and phylogenetic studies specifically for clownfish and more
generally for other related fish species of the family Pomacentridae.
PMID- 29342278
TI - DOSIMETRY OF ADULT AND PEDIATRIC PATIENTS FOR COMMON DIGITAL RADIOGRAPHY
EXAMINATIONS.
AB - The present work reports dosimetry data on adult and pediatric patients for some
common radiographic examinations during the standard hospital routine. The
measurements are the part of quality assurance program to determine radiation
exposures to patients in these examinations. The entrance skin doses (ESDs) of
the patients were measured from 2451 projection for 12 diagnostic examinations in
digital radiography (DR). The ESDs in adult patient were measured using
thermoluminescence dosemeters placed on the skin of the patient. In pediatric
patients, ESDs were evaluated from the measured air kerma with ionization
chamber, patient specific parameters and known values of machine exposure factors
during examinations. The third quartile values of ESDs are proposed as local
diagnostic reference levels (LDRLs) for radiographic examinations having
statistical significant number of exposures (n >= 20). The proposed LDRL values
are also compared with earlier published LDRL/DRL values.
PMID- 29342279
TI - Incidence and predictors of post-transplant lymphoproliferative disease after
kidney transplantation during adulthood and childhood: a registry study.
AB - Background: Differences in the epidemiology of post-transplant
lymphoproliferative disease (PTLD) between adult and paediatric kidney transplant
recipients remain unclear. Methods: Using the Australian and New Zealand Dialysis
and Transplant Registry (1963-2015), the cumulative incidences of PTLD in
children (age <20 years) and adults were calculated using a competing risk of
death model and compared with age-matched population-based data using
standardized incidence ratios (SIRs). Risk factors for PTLD were assessed using
Cox proportional hazards regression. Results: Among 23 477 patients (92% adult,
60% male), 505 developed PTLD, with 50 (10%) occurring in childhood recipients.
The 25-year cumulative incidence of PTLD was 3.3% [95% confidence interval (CI)
2.9-3.6] for adult recipients and 3.6% (95% CI 2.7-4.8) for childhood recipients.
Childhood recipients had a 30-fold increased risk of lymphoma compared with the
age-matched general population [SIR 29.5 (95% CI 21.9-38.8)], higher than adult
recipients [SIR 8.4 (95% CI 7.7-9.2)]. Epstein-Barr virus (EBV)-negative
recipient serology [adjusted hazard ratio (aHR) 3.33 (95% CI 2.21-5.01), P <
0.001], year of transplantation [aHR 0.93 for each year after the year 2000 (95%
CI 0.88-0.99), P = 0.02], induction with an agent other than anti-CD25 monoclonal
antibody [aHR 2.07 (95% CI 1.16-3.70), P = 0.01] and having diabetes [aHR 3.49
(95% CI 2.26-5.38), P < 0.001] were independently associated with PTLD.
Conclusions: Lymphoma occurs at similar rates in adult and paediatric recipients,
but has been decreasing since the year 2000. EBV-negative patients and those with
diabetes or induction agent other than anti-CD25 monoclonal antibody are at
substantially increased risk of PTLD.
PMID- 29342281
TI - Phenotypic analysis of HIV-1 E157Q integrase polymorphism and impact on
virological outcome in patients initiating an integrase inhibitor-based regimen.
AB - Objectives: To assess the phenotypic susceptibility of the E157Q polymorphism in
HIV-1 integrase (IN) and the virological outcome of patients infected with E157Q
mutated virus initiating an IN inhibitor (INI)-based regimen. Methods: This was a
multicentre study assessing IN sequences from INI-naive patients among 17 French
HIV clinical centres. E157Q site-directed mutants in pNL4.3 and pCRF02_AG
contexts were assessed in a recombinant phenotypic assay. Results: Prevalence of
the E157Q polymorphism was 2.7% among 8528 IN sequences from INI-naive patients
and its distribution was 1.7%, 5.6% and 2.2% in B, CRF02_AG and various non-B
subtypes, respectively. Thirty-nine INI-naive patients with E157Q-mutated virus
initiated an INI-based regimen. Among them, 15 had a viral load (VL) <50
copies/mL at initiation and virological suppression was maintained during the
first year of follow-up in all but two exhibiting a viral blip. Twenty-four
patients had a VL > 50 copies/mL at the time of INI-based regimen initiation.
Among them eight were receiving a first-line regimen and the only two patients
who did not reach VL < 50 copies/mL at week 24 were receiving elvitegravir. The
16 remaining patients were ART experienced in virological failure with drug
resistant viruses displaying several virological outcomes independently of the
genotypic susceptibility score. Phenotypic analyses showed a fold change in EC50
of 0.6, 0.9 and 1.9 for raltegravir, dolutegravir and elvitegravir, respectively,
in a subtype B context, and 1.1, 1.9 and 2.4 for raltegravir, dolutegravir and
elvitegravir, respectively, in a CRF02_AG context. Conclusions: Assessment of
virological response in 39 patients initiating an INI-based regimen with E157Q
mutated virus, in combination with phenotypic analysis, suggests that particular
attention should be paid to antiretroviral-naive patients and dolutegravir should
be preferentially used in these patients.
PMID- 29342280
TI - Epigenetic Differentiation of Natural Populations of Lilium bosniacum Associated
with Contrasting Habitat Conditions.
AB - Epigenetic variation in natural populations with contrasting habitats might be an
important element, in addition to the genetic variation, in plant adaptation to
environmental stress. Here, we assessed genetic, epigenetic, and cytogenetic
structure of the three Lilium bosniacum populations growing on distinct habitats.
One population was growing under habitual ecological conditions for this species
and the other two were growing under stress associated with high altitude and
serpentine soil. Amplified fragment length polymorphism and methylation-sensitive
amplification polymorphism analyses revealed that the three populations did not
differentiate genetically, but were clearly separated in three distinct clusters
according to DNA methylation profiles. Principal coordinate analysis showed that
overall epigenetic variation was closely related to habitat conditions. A new
methylation-sensitive amplification polymorphism scoring approach allowed
identification of mainly unmethylated (phiST = 0.190) and fully CpG methylated
(phiST = 0.118) subepiloci playing a role in overall population differentiation,
in comparison with hemimethylated sites (phiST = 0.073). In addition, unusual
rDNA repatterning and the presence of B chromosomes bearing 5S rDNA loci were
recorded in the population growing on serpentine soil, suggesting dynamic
chromosome rearrangements probably linked to global genome demethylation, which
might have reactivated some mobile elements. We discuss our results considering
our earlier data on morphology and leaf anatomy of several L. bosniacum
populations, and suggest a possible role of epigenetics as a key element in
population differentiation associated with environmental stress in these
particular lily populations.
PMID- 29342282
TI - Membrane fluxes, bypass flows, and sodium stress in rice: the influence of
silicon.
AB - Provision of silicon (Si) to roots of rice (Oryza sativa L.) can alleviate salt
stress by blocking apoplastic, transpirational bypass flow of Na+ from root to
shoot. However, little is known about how Si affects Na+ fluxes across cell
membranes. Here, we measured radiotracer fluxes of 24Na+, plasma membrane
depolarization, tissue ion accumulation, and transpirational bypass flow, to
examine the influence of Si on Na+ transport patterns in hydroponically grown,
salt-sensitive (cv. IR29) and salt-tolerant (cv. Pokkali) rice. Si increased
growth and lowered [Na+] in shoots of both cultivars, with minor effects in
roots; neither root nor shoot [K+] were affected. In IR29, Si lowered shoot [Na+]
via a large reduction in bypass flow, while in Pokkali, where bypass flow was
small and not affected by Si, this was achieved mainly via a growth dilution of
shoot Na+. Si had no effect on unidirectional 24Na+ fluxes (influx and efflux),
or on Na+-stimulated plasma-membrane depolarization, in either IR29 or Pokkali.
We conclude that, while Si can reduce Na+ translocation via bypass flow in some
(but not all) rice cultivars, it does not affect unidirectional Na+ transport or
Na+ cycling in roots, either across root cell membranes or within the bulk root
apoplast.
PMID- 29342284
TI - Two Ways to Kill a Patient.
AB - According to the Standard View, a doctor who withdraws life-sustaining treatment
does not kill the patient but rather allows the patient to die-an important
distinction, according to some. I argue that killing (and causing death) can be
understood in either of two ways, and given the relevant understanding, the
Standard View is insulated from typical criticisms. I conclude by noting several
problems for the Standard View that remain to be fully addressed.
PMID- 29342283
TI - Non-typhoidal Salmonella serovars associated with invasive and non-invasive
disease in the Lao People's Democratic Republic.
AB - Background: Invasive non-typhoidal Salmonella (iNTS) disease is a well-described
cause of mortality in children and human immunodeficiency virus (HIV)-infected
adults in sub-Saharan Africa. Additionally, there is an ill-defined burden of
iNTS disease in Southeast Asia. Methods: Aiming to investigate the causative
serovars of non-invasive and iNTS disease and their associated antimicrobial
susceptibility profiles in the Lao People's Democratic Republic, we performed
multilocus sequence typing and antimicrobial susceptibility profiling on 168 NTS
(63 blood and 105 faecal) organisms isolated in Lao between 2000 and 2012.
Results: Six different serovars were isolated from blood; Salmonella enterica
serovar Enteritidis (n=28), S. enterica serovar Typhimurium (n=19) and S.
enterica serovar Choleraesuis (n=11) accounted for >90% (58/63) of the iNTS
disease cases. In contrast, the isolates from diarrhoeal faeces were comprised of
18 different serovars, the mostly commonly identified being S. enterica
Typhimurium (n=28), S. enterica Weltevreden (n=14) and S. enterica Stanley
(n=15). S. enterica Enteritidis and S. enterica Choleraesuis were significantly
more associated with systemic disease than diarrhoeal disease in this patient
group (p<0.001). Conclusions: We find a differing distribution of Salmonella
sequence types/serovars between those causing iNTS disease and non-invasive
disease in Lao. We conclude that there is a small but not insignificant burden of
iNTS disease in Lao. Further clinical and epidemiological investigations are
required to assess mortality and the role of comorbidities such as HIV.
PMID- 29342285
TI - Serial Participation and the Ethics of Phase 1 Healthy Volunteer Research.
AB - Phase 1 healthy volunteer clinical trials-which financially compensate subjects
in tests of drug toxicity levels and side effects-appear to place pressure on
each joint of the moral framework justifying research. In this article, we review
concerns about phase 1 trials as they have been framed in the bioethics
literature, including undue inducement and coercion, unjust exploitation, and
worries about compromised data validity. We then revisit these concerns in light
of the lived experiences of serial participants who are income-dependent on phase
1 trials. We show how participant experiences shift attention from discrete
exchanges, behaviors, and events in the research enterprise to the ongoing and
dynamic patterns of serial participation in which individual decision-making is
embedded in collective social and economic conditions and shaped by institutional
policies. We argue in particular for the ethical significance of structurally
diminished voluntariness, routine powerlessness in setting the terms of exchange,
and incentive structures that may promote pharmaceutical interests but encourage
phase 1 healthy volunteers to skirt important rules.
PMID- 29342286
TI - The Ethics of General Population Preventive Genomic Sequencing: Rights and Social
Justice.
AB - Advances in DNA sequencing technology open new possibilities for public health
genomics, especially in the form of general population preventive genomic
sequencing (PGS). Such screening programs would sit at the intersection of public
health and preventive health care, and thereby at once invite and resist the use
of clinical ethics and public health ethics frameworks. Despite their
differences, these ethics frameworks traditionally share a central concern for
individual rights. We examine two putative individual rights-the right not to
know, and the child's right to an open future-frequently invoked in discussions
of predictive genetic testing, in order to explore their potential contribution
to evaluating this new practice. Ultimately, we conclude that traditional
clinical and public health ethics frameworks, and these two rights in particular,
should be complemented by a social justice perspective in order adequately to
characterize the ethical dimensions of general population PGS programs.
PMID- 29342288
TI - Association between ABCG2 rs2231142 and poor response to allopurinol: replication
and meta-analysis.
AB - Objective: ABCG2 rs2231142 (Q141K) has been reported to be associated with poor
response to allopurinol, while there are conflicting data on the association
between the genetically independent ABCG2 rs10011796 variant and allopurinol
response. The aim of this study was to replicate the association of ABCG2
rs2231142 and rs10011796 with allopurinol response and perform a meta-analysis.
Methods: Participants in the Long-term Allopurinol Safety Study Evaluating
Outcomes in Gout Patients (LASSO) (n = 299) were studied. In patients with
evidence of adherence to allopurinol therapy (plasma oxypurinol >20 MUmol/l),
good response was defined as serum urate <6 mg/dl on allopurinol ?300 mg/day and
poor response as serum urate ? 6 mg/dl despite allopurinol >300 mg/day.
Association of rs2231142 and rs10011796 with poor response was tested in logistic
regression models that included age, sex, BMI, ethnicity and estimated glomerular
filtration rate. Results from the LASSO study and a subset of participants in the
Genetics of Gout in Aotearoa New Zealand study (n = 296, including 264 from a
previously published report) were combined by meta-analysis. Results: There was
evidence for association of rs2231142 with allopurinol response [odds ratio (OR)
= 2.35, P = 7.3 * 10-4] but not for rs10011796 (OR = 1.21, P = 0.33) in the LASSO
cohort using an adjusted logistic regression model. Meta-analysis provided
evidence of a significant association of rs2231142 with allopurinol response (OR
= 2.43, P = 6.2 * 10-7), but not rs10011796 (OR = 1.06, P = 0.69). Conclusion:
This study has confirmed the significant association of ABCG2 rs2231142 with poor
response to allopurinol.
PMID- 29342290
TI - Chronic kidney disease and stroke: more observations but no trials.
PMID- 29342287
TI - To the Brain and Back: Migratory Paths of Dendritic Cells in Multiple Sclerosis.
AB - Migration of dendritic cells (DC) to the central nervous system (CNS) is a
critical event in the pathogenesis of multiple sclerosis (MS). While up until
now, research has mainly focused on the transmigration of DC through the blood
brain barrier, experimental evidence points out that also the choroid plexus and
meningeal vessels represent important gateways to the CNS, especially in early
disease stages. On the other hand, DC can exit the CNS to maintain immunological
tolerance to patterns expressed in the CNS, a process that is perturbed in MS.
Targeting trafficking of immune cells, including DC, to the CNS has demonstrated
to be a successful strategy to treat MS. However, this approach is known to
compromise protective immune surveillance of the brain. Unravelling the migratory
paths of regulatory and pathogenic DC within the CNS may ultimately lead to the
design of new therapeutic strategies able to selectively interfere with the
recruitment of pathogenic DC to the CNS, while leaving host protective mechanisms
intact.
PMID- 29342289
TI - Recent advances in kidney transplantation: a viewpoint from the Descartes
advisory board.
AB - Transplantation medicine is a rapidly evolving field. Keeping afloat of the
published literature to offer the best clinical care to our patients is a
daunting task. As part of its educational mission, the Descartes advisory board
identified seven topics in kidney transplantation where there has been
substantial progresses over the last years: kidney allocation within
Eurotransplant; kidney exchange strategies; kidney machine perfusion strategies;
the changing landscape of anti-human leukocyte antigen (HLA) antibodies; the new
immunosuppressive drugs in the pipeline; strategies for immunosuppression
minimization; and the continuous enigma of focal segmental glomerular sclerosis
recurrence after transplantation. Here, we have summarized the main knowledge and
the main challenges of these seven topics with the aim to provide transplant
professionals at large with key bullet points to successfully understand these
new concepts.
PMID- 29342291
TI - PORTUGUESE STUDY OF MEAN GLANDULAR DOSE IN MAMMOGRAPHY AND COMPARISON WITH
EUROPEAN REFERENCES.
AB - To characterise the mean glandular dose (MGD) in a sample of healthcare providers
for digital mammography in Portugal. To compare the achieved values with European
references. The MGD was measured on a poly-methyl-methacrylate phantom (45 mm)
for each system using dosimeters. In addition, MGD was estimated using exposure
settings collected from mammography exams in clinical context. Data were
collected from 25 computed-radiography systems (CR) and 13 integrated digital
(DR). For both measurements (phantom and clinical exposures), the average MGD for
CR was higher compared to the DR. For CR the mean MGD was 1.85 mGy (CC
projection) and 2.10 mGy (MLO projection). For DR systems the corresponding
values were 1.54 mGy (CC) and 1.68 mGy (MLO). The average MGD obtained using both
methods and for both technologies is within the acceptable reference range
proposed by European guidelines (<2.5 mGy). Dose Reference Levels implementation
should be the next step to optimise mammography practice in Portugal.
PMID- 29342292
TI - Clinical utility of the global anti-phospholipid syndrome score for risk
stratification: a pooled analysis.
AB - Objective: Recently, our group conceived a risk score for clinical manifestations
of APS (the global APS score, or GAPSS) that takes into account the combination
of independent cardiovascular risk factors and the aPL positivity profile. These
include hyperlipidaemia, arterial hypertension, aCL, anti-beta2 glycoprotein-I,
aPS-PT and the LA. A complementary version, the adjusted GAPSS (aGAPSS), which
excludes aPS-PT, was also designed. The aim of our study was to systematically
review the literature to assess the clinical utility of the GAPSS and aGAPSS for
risk stratification of any APS clinical manifestation. Methods: We pooled data
from available cohort studies, including a total of 10 studies, comprising 2273
patients, in which the GAPSS has been applied. A search strategy was developed a
priori to identify an available cohort that reported findings which investigated
the clinical utility of GAPSS or aGAPSS. Results: Seven studies used the GAPSS in
their cohort, whereas three studies used the aGAPSS. In brief, we found a
statistically significant difference in the cumulative GAPSS and aGAPSS between
patients that experienced an arterial and/or venous thrombotic event [cumulative
mean GAPSS (s.d.) 10.6 (4.74) and aGAPSS 7.6 (3.95)], patients without any
thrombotic manifestation [cumulative GAPSS 7.01 (5.46) and aGAPSS 4.9 (4.33)] and
patients with pregnancy morbidity [cumulative GAPSS 8.79 (2.59) and aGAPSS 6.7
(2.8)]. The highest levels of GAPSS were found in patients that experienced
arterial thrombosis [mean GAPSS 12.2 (5.2)] and patients that experienced any
recurrences of clinical manifestations of APS [mean GAPSS 13.7 (3.1)].
Conclusion: GAPSS may represent a useful tool to assess the thrombosis or
pregnancy loss risk in aPL-positive patients, switching from the concept of aPL
as a sole diagnostic antibody to aPL as risk factors for clinical events.
PMID- 29342293
TI - Genetic Analyses in Small-for-Gestational-Age Newborns.
AB - Context: Small for gestational age (SGA) can be the result of fetal growth
restriction, which is associated with perinatal morbidity and mortality.
Mechanisms that control prenatal growth are poorly understood. Objective: The aim
of the current study was to gain more insight into prenatal growth failure and
determine an effective diagnostic approach in SGA newborns. We hypothesized that
one or more copy number variations (CNVs) and disturbed methylation and sequence
variants may be present in genes associated with fetal growth. Design: A
prospective cohort study of subjects with a low birth weight for gestational age.
Setting: The study was conducted at an academic pediatric research institute.
Patients: A total of 21 SGA newborns with a mean birth weight below the first
centile and a control cohort of 24 appropriate-for-gestational-age newborns were
studied. Interventions: Array comparative genomic hybridization, genome-wide
methylation studies, and exome sequencing were performed. Main Outcome Measures:
The numbers of CNVs, methylation disturbances, and sequence variants. Results:
The genetic analyses demonstrated three CNVs, one systematically disturbed
methylation pattern, and one sequence variant explaining SGA. Additional
methylation disturbances and sequence variants were present in 20 patients. In 19
patients, multiple abnormalities were found. Conclusion: Our results confirm the
influence of a large number of mechanisms explaining dysregulation of fetal
growth. We concluded that CNVs, methylation disturbances, and sequence variants
all contribute to prenatal growth failure. These genetic workups can be an
effective diagnostic approach in SGA newborns.
PMID- 29342294
TI - Factors affecting public health nurses' satisfaction with the preparedness and
response of disaster relief operations at nuclear emergencies.
PMID- 29342295
TI - Empagliflozin Treatment Is Associated With Improved beta-Cell Function in Type 2
Diabetes Mellitus.
AB - Objective: To examine whether lowering plasma glucose concentration with the
sodium-glucose transporter-2 inhibitor empagliflozin improves beta-cell function
in patients with type 2 diabetes mellitus (T2DM). Methods: Patients with T2DM (N
= 15) received empagliflozin (25 mg/d) for 2 weeks. beta-Cell function was
measured with a nine-step hyperglycemic clamp (each step, 40 mg/dL) before and at
48 hours and at 14 days after initiating empagliflozin. Results: Glucosuria was
recorded on days 1 and 14 [mean +/- standard error of the mean (SEM), 101 +/- 10
g and 117 +/- 11 g, respectively] after initiating empagliflozin, as were
reductions in fasting plasma glucose levels (25 +/- 6 mg/dL and 38 +/- 8 mg/dL,
respectively; both P < 0.05). After initiating empagliflozin and during the
stepped hyperglycemic clamp, the incremental area under the plasma C-peptide
concentration curve increased by 48% +/- 12% at 48 hours and 61% +/- 10% at 14
days (both P < 0.01); glucose infusion rate increased by 15% on day 3 and 16% on
day 14, compared with baseline (both P < 0.05); and beta-cell function, measured
with the insulin secretion/insulin resistance index, increased by 73% +/- 21% at
48 hours and 112% +/- 20% at 14 days (both P < 0.01). beta-cell glucose
sensitivity during the hyperglycemic clamp was enhanced by 42% at 14 hours and
54% at 14 days after initiating empagliflozin (both P < 0.01). Conclusion:
Lowering the plasma glucose concentration with empagliflozin in patients with
T2DM augmented beta-cell glucose sensitivity and improved beta-cell function.
PMID- 29342297
TI - AN EXACT GOODNESS-OF-FIT TEST BASED ON THE OCCUPANCY PROBLEMS TO STUDY ZERO
INFLATION AND ZERO-DEFLATION IN BIOLOGICAL DOSIMETRY DATA.
AB - The goal in biological dosimetry is to estimate the dose of radiation that a
suspected irradiated individual has received. For that, the analysis of
aberrations (most commonly dicentric chromosome aberrations) in scored cells is
performed and dose response calibration curves are built. In whole body
irradiation (WBI) with X- and gamma-rays, the number of aberrations in samples is
properly described by the Poisson distribution, although in partial body
irradiation (PBI) the excess of zeros provided by the non-irradiated cells leads,
for instance, to the Zero-Inflated Poisson distribution. Different methods are
used to analyse the dosimetry data taking into account the distribution of the
sample. In order to test the Poisson distribution against the Zero-Inflated
Poisson distribution, several asymptotic and exact methods have been proposed
which are focused on the dispersion of the data. In this work, we suggest an
exact test for the Poisson distribution focused on the zero-inflation of the data
developed by Rao and Chakravarti (Some small sample tests of significance for a
Poisson distribution. Biometrics 1956; 12 : 264-82.), derived from the problems
of occupancy. An approximation based on the standard Normal distribution is
proposed in those cases where the computation of the exact test can be tedious. A
Monte Carlo Simulation study was performed in order to estimate empirical
confidence levels and powers of the exact test and other tests proposed in the
literature. Different examples of applications based on in vitro data and also
data recorded in several radiation accidents are presented and discussed. A Shiny
application which computes the exact test and other interesting goodness-of-fit
tests for the Poisson distribution is presented in order to provide them to all
interested researchers.
PMID- 29342298
TI - Periodontal Disease Assessed Using Clinical Dental Measurements and Cancer Risk
in the ARIC Study.
AB - Background: While evidence is increasingly consistent with a positive association
between periodontitis and cancer risk, most studies have relied on self-reported
periodontitis. In this study, we prospectively evaluated the association of
periodontal disease severity with cancer risk in black and white older adults in
a cohort study that included a dental examination. Methods: Included were 7466
participants in the Atherosclerosis Risk in Communities study cohort who at visit
4 (1996-1998) reported being edentulous or underwent the dental examination.
Probing depth and gingival recession were measured at six sites on all teeth;
these measurements were used to define periodontal disease severity. Incident
cancers (n = 1648) and cancer deaths (n = 547) were ascertained during a median
of 14.7 years of follow-up. All statistical tests were two-sided. Results: An
increased risk of total cancer (hazard ratio [HR] = 1.24, 95% confidence interval
[CI] = 1.07 to 1.44, Ptrend = .004) was observed for severe periodontitis (>30%
of sites with attachment loss >3 mm) compared with no/mild periodontitis (<10% of
sites with attachment loss >3 mm), adjusting for smoking and other factors.
Strong associations were observed for lung cancer (HR = 2.33, 95% CI = 1.51 to
3.60, Ptrend < .001), and elevated risks were noted for colorectal cancer for
severe periodontitis, which were significant among never smokers (HR = 2.12, 95%
CI = 1.00 to 4.47). Associations were generally weaker, or not apparent among
black participants, except for lung and colorectal cancers, where associations
were similar by race. No associations were observed for breast, prostate, or
hematopoietic and lymphatic cancer risk. Conclusions: This study provides
additional evidence that cancer risk, especially for lung and colorectal cancer,
is elevated in individuals with periodontitis. Additional research is needed to
understand cancer site-specific and racial differences in findings.
PMID- 29342299
TI - Benefit of left atrial appendage electrical isolation for persistent and long
standing persistent atrial fibrillation: a systematic review and meta-analysis.
AB - Aims: The long-term outcomes of left atrial appendage electrical isolation
(LAAEI) in patients with non-paroxysmal atrial fibrillation (AF) have
corroborated the significant role of the LAA in this arrhythmia. We sought to
investigate the incremental benefit of LAAEI in patients undergoing catheter
ablation for persistent AF or long-standing persistent AF (LSPAF). Methods and
results: A systematic review of Medline, Cochrane, and Embase for all the
clinical studies in which assessment LAAEI in non-paroxysmal AF patients was
performed. The benefit of LAAEI in patients with AF was analysed from seven
studies that enrolled a total of 930 patients [mean age 63 +/- 5 years; male:
69%]. All studies included patients with either persistent AF or LSPAF or the
combination of them. The overall freedom from all-arrhythmia recurrence at 12
months of follow-up off antiarrhythmic medications in patients who underwent
LAAEI was 75.5% vs. 43.9% in those in whom only standard ablation was performed
[56% relative reduction and 31.6% absolute reduction; risk ratio (RR) 0.44, 95%
confidence interval (95% CI) 0.31-0.64; P < 0.0001]. The rate of ischaemic stroke
in the LAAEI group was 0.4% and in the control group 2.1% at 12 months follow-up
(RR 0.40, 95% CI 0.12-1.30; P = 0.13). Acute complications rates were identical
between groups [LAAEI 5.5%, control 5.5% (RR 0.99, 95% CI 0.46-2.16; P = 0.99)].
Conclusion: Left atrial appendage electrical isolation in addition to standard
ablation appears to have a substantial incremental benefit to achieve freedom
from ALL atrial arrhythmias in patients with persistent AF and LSPAF without
increasing acute procedural complications and without raising the risk of
ischaemic stroke.
PMID- 29342301
TI - Subtyping Bladder Cancers: Biology vs Bioinformatics.
PMID- 29342300
TI - Metastatic joint involvement or inflammatory arthritis? A conundrum with immune
checkpoint inhibitor-related adverse events.
PMID- 29342302
TI - Determination of the appropriate physical density of internal metallic ports in
temporary tissue expanders for the treatment planning of post-mastectomy
radiation therapy.
AB - Some patients undergoing breast reconstruction require post-mastectomy radiation
therapy, but the metallic ports used in temporary tissue expanders attenuate the
X-rays. In this study, we evaluated by the film method, the attenuation of 4 MV
and 6 MV X-rays after passing through a metallic port, with the aim of
identifying a useful method for determining the appropriate density to use in the
radiation treatment planning system (RTPS), taking into account the distance
between the metallic port and the targets. Radiochromic film was used to measure
depth doses after the X-rays passed through the metallic port. The physical
density allotted to the metal port portion was varied on the RTPS within the
range 1-16 g/cm3, and the physical density values were calculated that best
reproduced the depth-dose distribution extrapolated from the film method. When
the metallic port was orientated perpendicularly, the attenuation of the X-rays
peaked at ~7% at both 4 MV and 6 MV. In the parallel orientation, the X-rays were
attenuated by up to ~40% at 4 MV and by up to ~30% at 6 MV. We estimated the
optimum physical density to be 9.8 g/cm3, which yielded the best fit with the
actual measurements. We demonstrated the most likely range for the target depth
from the CT images of actual patients and, within this range, we identified the
optimum physical density at which the measured and calculated values were most
consistent with each other.
PMID- 29342303
TI - Biomarkers for Tobacco Exposures, Toxicology, Regulation, and Cessation.
PMID- 29342304
TI - Introduction of standardised tobacco packaging during a 12-month transition
period: Findings from small retailers in the United Kingdom.
AB - Introduction: Factory-made cigarettes (FMC) and roll-your-own (RYO) tobacco have
had to be produced in standardised packaging since 20th May 2016 in the United
Kingdom, with a minimum pack size of 20 sticks for FMC and 30 grams for RYO.
Manufacturers and retailers were given a 12-month transition period. Methods: An
observational study was conducted using monthly Electronic Point of Sale data
from 500 small retailers in England, Scotland, and Wales, between May 2016 and
May 2017. The 20 top selling tobacco products (15 FMC, 5 RYO) were monitored to
observe when standardised packs were first introduced, the proportion of
retailers selling each fully branded and standardised product, and the average
number of monitored fully branded and standardised products sold by each
retailer. The number of unique tobacco-related product codes sold by each
retailer was also recorded each month. Results: Eighteen of the fully branded
products continued to be sold throughout the transition period and no
standardised variants were sold in the first five months. It was not until month
eleven that the average number of standardised products sold by retailers
exceeded the fully branded products. The average number of unique tobacco-related
product codes sold by each retailer decreased by a third over the transition
period. Conclusions: Tobacco companies used the transition period to delay the
removal of fully branded products and gradually introduce standardised variants.
This staggered introduction may have mitigated some of the immediate intended
effects of the legislation by desensitising consumers to new pack designs.
Implications: Evaluation research from countries which have introduced
standardised packaging for tobacco products is key to help inform future
implementation. This is the first study to monitor the transition from fully
branded to standardised products using real-time retail data. The findings
demonstrate that tobacco companies delayed the introduction of standardised
products and removal of fully branded packaging. Countries seeking to introduce
standardised packaging should consider what length of transition is allowed, as
the protracted 12 month period in the UK appeared longer than needed to
transition stockholding and may have mitigated immediate intended effects by
desensitising consumers to new pack designs.
PMID- 29342305
TI - ANALYSIS OF ELECTRIC FIELD STRENGTH AND POWER AROUND SELECTED MOBILE BASE
STATIONS.
AB - The analysis of channel power and electric field strength at various locations
from mobile base stations using power sensor, spectrum analyzer and log-periodic
antenna revealed maximum potential exposure between the range of 61.1 and 254.7
m. Generally, the potential exposure values ranged from 0.0717 to 0.8950 mW m-2
with a maximum deviation of 22.22%. GSM900 was found to be more pronounced than
GSM1800 and UMTS2100. Though the results complied with ICNIRP reference levels
with a wide margin of 0.01%, it was higher than some previous work and South
African mean value of 0.16 mW m-2, agreed with similar work elsewhere but lower
than a global average value of 0.730 mW m-2.
PMID- 29342306
TI - Prevalence and Factors Associated with Diarrhoea among Children between 6 and 59
Months of Age in Mwanza City Tanzania.
AB - Background: Childhood diarrhoea is a global public health problem especially in
unplanned settlements of low- and middle-income countries. Different studies have
associated household settlement and childhood diarrhoea, but the prevalence and
risk factors associated with childhood diarrhoea at the community level are not
clearly known. Method: A community-based cross-sectional study was performed to
determine the prevalence and risk factors associated with diarrhoea in among 480
children between 6 and 59 months of age in Mwanza city from June to August 2016.
Risk factors associated with childhood diarrhoea in Mwanza city were determined
using univariate, bivariate and multivariate analysis. Results: The study showed
a prevalence of diarrhoea of 20.4% and an association between type of settlement
and childhood diarrhoea (p < 0.001) in a chi-square analysis. During bivariate
analysis, and logistic regression, after controlling for other factors, unplanned
settlement was significantly associated with childhood diarrhoea (odds
ratio=3.475, p < 0.001 and AOR=3.469, p < 0.001). Other factors associated with
childhood diarrhoea were behaviour of mother washing hands before preparing food
(AOR = 0, 193, p < 0.001), mother washing hands after changing child's napkins
(AOR = 0.544, p < 0.036) and the behaviour of the child washing hands after
toilet (AOR = 0.447, p < 0.006). Conclusion: Risk factors associated with
childhood diarrhoea in Mwanza city are unplanned settlement and behaviour of
mother and child washing hands during critical time; hence, continuous community
health promotion insisting on washing hands with soap and water during critically
time is the best method for fighting childhood diarrhoea in Mwanza city.
PMID- 29342308
TI - Chronic kidney disease burden among African migrants in three European countries
and in urban and rural Ghana: the RODAM cross-sectional study.
AB - Background: Chronic kidney disease (CKD) is a major burden among sub-Saharan
African (SSA) populations. However, differences in CKD prevalence between rural
and urban settings in Africa, and upon migration to Europe are unknown. We
therefore assessed the differences in CKD prevalence among homogenous SSA
population (Ghanaians) residing in rural and urban Ghana and in three European
cities, and whether conventional risk factors of CKD explained the observed
differences. Furthermore, we assessed whether the prevalence of CKD varied among
individuals with hypertension and diabetes compared with individuals without
these conditions. Methods: For this analysis, data from Research on Obesity &
Diabetes among African Migrants (RODAM), a multi-centre cross-sectional study,
were used. The study included a random sample of 5607 adult Ghanaians living in
Europe (1465 Amsterdam, 577 Berlin, 1041 London) and Ghana (1445 urban and 1079
rural) aged 25-70 years. CKD status was defined according to severity of kidney
disease using the combination of glomerular filtration rate (G1-G5) and
albuminuria (A1-A3) levels as defined by the 2012 Kidney Disease: Improving
Global Outcomes severity classification. Comparisons among sites were made using
logistic regression analysis. Results: CKD prevalence was lower in Ghanaians
living in Europe (10.1%) compared with their compatriots living in Ghana (13.3%)
even after adjustment for age, sex and conventional risk factors of CKD [adjusted
odds ratio (OR) = 0.70, 95% confidence interval (CI) 0.56-0.88, P = 0.002]. CKD
prevalence was markedly lower among Ghanaian migrants with hypertension (adjusted
OR = 0.54, 0.44-0.76, P = 0.001) and diabetes (adjusted OR = 0.37, 0.22-0.62, P =
0.001) compared with non-migrant Ghanaians with hypertension and diabetes. No
significant differences in CKD prevalence was observed among non-migrant
Ghanaians and migrant Ghanaians with no hypertension and diabetes. Among Ghanaian
residents in Europe, the odds of CKD were lower in Amsterdam than in Berlin,
while among Ghanaian residents in Ghana, the odds of CKD were lower in rural
Ghana (adjusted OR = 0.68, 95% CI 0.53-0.88, P = 0.004) than in urban Ghana, but
these difference were explained by conventional risk factors. Conclusion: Our
study shows important differences in CKD prevalence among Ghanaians living in
Europe compared with those living in Ghana, independent of conventional risk
factors, with marked differences among those with hypertension and diabetes.
Further research is needed to identify factors that might explain the observed
difference across sites to implement interventions to reduce the high burden of
CKD, especially in rural and urban Ghana.
PMID- 29342307
TI - Using Phylogenomic Data to Explore the Effects of Relaxed Clocks and Calibration
Strategies on Divergence Time Estimation: Primates as a Test Case.
AB - Primates have long been a test case for the development of phylogenetic methods
for divergence time estimation. Despite a large number of studies, however, the
timing of origination of crown Primates relative to the Cretaceous-Paleogene (K
Pg) boundary and the timing of diversification of the main crown groups remain
controversial. Here, we analysed a data set of 372 taxa (367 Primates and 5
outgroups, 3.4 million aligned base pairs) that includes nine primate genomes. We
systematically explore the effect of different interpretations of fossil
calibrations and molecular clock models on primate divergence time estimates. We
find that even small differences in the construction of fossil calibrations can
have a noticeable impact on estimated divergence times, especially for the oldest
nodes in the tree. Notably, choice of molecular rate model (autocorrelated or
independently distributed rates) has an especially strong effect on estimated
times, with the independent rates model producing considerably more ancient age
estimates for the deeper nodes in the phylogeny. We implement thermodynamic
integration, combined with Gaussian quadrature, in the program MCMCTree, and use
it to calculate Bayes factors for clock models. Bayesian model selection
indicates that the autocorrelated rates model fits the primate data substantially
better, and we conclude that time estimates under this model should be preferred.
We show that for eight core nodes in the phylogeny, uncertainty in time estimates
is close to the theoretical limit imposed by fossil uncertainties. Thus, these
estimates are unlikely to be improved by collecting additional molecular sequence
data. All analyses place the origin of Primates close to the K-Pg boundary,
either in the Cretaceous or straddling the boundary into the Palaeogene.
PMID- 29342310
TI - Temporal Trends of Sources of Cigarettes among U.S. High School Students: 2001
2015.
AB - Introduction: Restricting the supply of cigarettes to youth plays an important
role in reducing youth smoking. Methods: The study included data from 8 years of
the national Youth Risk Behavior Survey (YRBS) from 2001 to 2015 with 99,572 high
school students less than 18 years old. Data were weighted to provide national
estimates of the temporal trends of cigarette sources. Each cigarette source was
analyzed by a separate multivariable logistic regression model and the linear
trend odds ratio (aOR) was adjusted by age, sex, race/ethnicity, and smoking
frequency. Results: The current smoking prevalence among U.S. high school
students less than 18 years of age declined from 26.9% in 2001 to 9.9% in 2015.
Among current smokers, we found an overall downward trend of buying cigarettes in
a store (aOR=0.98, CI [0.96 - 1.00]) and an overall upward trend of getting them
"some other way" (aOR=1.03, CI [1.01 - 1.05]). The prevalence of purchasing
cigarettes in a store significantly declined among smokers aged 16-17, male
smokers, white smokers, and daily smokers, but not among other categories. The
prevalence of getting cigarettes "some other way" significantly increased across
all groups except Hispanic smokers and medium-level or daily smokers.
Conclusions: The proportion of high school students reporting that they bought
cigarettes from a store has been declining over the years, while the proportion
of high schoolers reporting that they got cigarettes "some other way" has been
increasing. The temporal trends also varied by age, sex, race/ethnicity, and
smoking frequency. Implications: Patterns of high school student access to
cigarettes have changed from 2001 to 2015, with access from "some other way"
becoming more prevalent. The differences in cigarette acquisition by age, sex,
race/ethnicity, and smoking frequency highlight the importance of implementing
tailored policies and interventions to reduce youth access to cigarettes and
prevent youth from smoking. Clinical Trial Registration: This is not a clinical
trial.
PMID- 29342309
TI - Prognostic Power of a Tumor Differentiation Gene Signature for Bladder Urothelial
Carcinomas.
AB - Background: Muscle-invasive bladder cancers (MIBCs) cause approximately 150 000
deaths per year worldwide. Survival for MIBC patients is heterogeneous, with no
clinically validated molecular markers that predict clinical outcome. Non-MIBCs
(NMIBCs) generally have favorable outcome; however, a portion progress to MIBC.
Hence, development of a prognostic tool that can guide decision-making is crucial
for improving clinical management of bladder urothelial carcinomas. Methods:
Tumor grade is defined by pathologic evaluation of tumor cell differentiation,
and it often associates with clinical outcome. The current study extrapolates
this conventional wisdom and combines it with molecular profiling. We developed
an 18-gene signature that molecularly defines urothelial cellular
differentiation, thus classifying MIBCs and NMIBCs into two subgroups: basal and
differentiated. We evaluated the prognostic capability of this "tumor
differentiation signature" and three other existing gene signatures including the
The Cancer Genome Atlas (TCGA; 2707 genes), MD Anderson Cancer Center (MDA; 2252
genes/2697 probes), and University of North Carolina at Chapel Hill (UNC; 47
genes) using five gene expression data sets derived from MIBC and NMIBC patients.
All statistical tests were two-sided. Results: The tumor differentiation
signature demonstrated consistency and statistical robustness toward stratifying
MIBC patients into different overall survival outcomes (TCGA cohort 1, P = .03;
MDA discovery, P = .009; MDA validation, P = .01), while the other signatures
were not as consistent. In addition, we analyzed the progression (Ta/T1
progressing to >=T2) probability of NMIBCs. NMIBC patients with a basal tumor
differentiation signature associated with worse progression outcome (P = .008).
Gene functional term enrichment and gene set enrichment analyses revealed that
genes involved in the biologic process of immune response and inflammatory
response are among the most elevated within basal bladder cancers, implicating
them as candidates for immune checkpoint therapies. Conclusions: These results
provide definitive evidence that a biology-prioritizing clustering methodology
generates meaningful insights into patient stratification and reveals targetable
molecular pathways to impact future therapeutic approach.
PMID- 29342311
TI - Nonmotor manifestations in ALS patients with tracheostomy and invasive
ventilation.
PMID- 29342312
TI - Maladaptive repetitive thought as a transdiagnostic phenomenon and treatment
target: An integrative review.
AB - OBJECTIVE: Maladaptive repetitive thought (RT), the frequent and repetitive
revisiting of thoughts or internal experiences, is associated with a range of
psychopathological processes and disorders. We present a synthesis of prior
research on maladaptive RT and develop a framework for elucidating and
distinguishing between five forms of maladaptive RT. METHOD: In addition to the
previously studied maladaptive RT (worry, rumination, and obsession), this
framework is used to identify two additional forms of maladaptive RT (yearning
and interoceptive RT). We then present a review of extant psychotherapy
intervention research targeting maladaptive RT, focusing both on specific
empirically based treatment strategies, and also constructs within treatments
that impact maladaptive RT. CONCLUSION: The paper concludes with recommendations
for future basic and intervention research on maladaptive RT and related
psychopathologies.
PMID- 29342313
TI - Collagen XII myopathy with rectus femoris atrophy and collagen XII retention in
fibroblasts.
AB - INTRODUCTION: Mutation in the collagen XII gene (COL12A1) was recently reported
to induce Bethlem myopathy. We describe a family affected by collagen XII-related
myopathy in 3 generations. METHODS: Systematic interview, clinical examination,
skin biopsies, and MRI of muscle were used. RESULTS: The phenotype was
characterized by neonatal hypotonia, contractures, and delayed motor development
followed by resolution of contractures and a motor performance limited by reduced
endurance. DNA analyses revealed a novel donor splice-site mutation in COL12A1
(c.8100 + 2T>C), which segregated with clinical affection and abnormal collagen
XII retention in fibroblasts. MRI disclosed a selective wasting of the rectus
femoris muscle. DISCUSSION: COL12A1 mutations should be considered in patients
with a mild Bethlem phenotype who present with selective wasting of the rectus
femoris, absence of the outside-in phenomenon on MRI, and abnormal collagen XII
retention in fibroblasts. Muscle Nerve 57: 1026-1030, 2018.
PMID- 29342314
TI - Fatigue is a relevant outcome in patients with myasthenia gravis.
AB - INTRODUCTION: Patients with myasthenia gravis often experience fatigue, but its
effect on quality of life (QoL) is underestimated, and fatigue is rarely measured
in clinical trials. METHODS: Two hundred fifty-seven myasthenic patients
completed the Neuro-QoL-Fatigue and measures of disease severity and QoL. We
studied the relationship between fatigue and clinical and demographic variables.
Finally, we studied the responsiveness of the Neuro-QoL-Fatigue in 95 patients
receiving treatments for myasthenia and estimated the minimal important
difference (MID). RESULTS: Fatigue correlated with greater disease severity (r =
0.52-0.69, P < 0.0001) and worse QoL (r = 0.65-0.75, P < 0.0001). Patients in
remission, with minimal manifestations, and pure ocular symptoms reported minimal
fatigue. Regression modeling showed that, in addition to its relationship with
disease severity, fatigue was worse in females, patients with generalized
disease, and those with anxiety/depression. Fatigue improved after
immunomodulation (P < 0.0001), and the MID was 5.3 points. DISCUSSION: Fatigue in
myasthenia correlates with disease severity, affects QoL, and can improve after
treatment. Muscle Nerve 58: 197-203, 2018.
PMID- 29342315
TI - Oxidation of Methylalumoxane Oligomers.
AB - The anions formed from methylalumoxane (MAO) and suitable donors (e.g.
octamethyltrisiloxane) are amenable to mass spectrometric (MS) analysis. Their
composition as deduced from this data allows direct insight into the chemical
transformations of their neutral precursors. One such process is oxidation, which
is well-known to be facile for MAO without any clear idea of what actually occurs
at a molecular level. Addition of O2 to MAO results in immediate gelation, but MS
analysis reveals no corresponding change to the composition of the principal
oligomeric anions. A slow (hours) reaction does occur that involves net
incorporation of Me2 AlOMe into the oligomeric anions, and the identities of the
OMe-containing anions were confirmed by 1 H NMR spectroscopy, MS/MS analysis, and
addition of an authentic sample of Me2 AlOMe to MAO. The result tallies with the
fact that addition of O2 to MAO produces Me2 AlOMe from free Me3 Al which
eventually leads to formation of oxidized MAO oligomers and changes in ion
abundance. Aging of the oxygenated MAO results in further growth of the oligomers
similar to that of the non-oxidized species. Mass spectrometric analysis
therefore reveals useful insights into the environmental history of a given MAO
batch.
PMID- 29342316
TI - Solvent-Free Enzyme Activity: Quick, High-Yielding Mechanoenzymatic Hydrolysis of
Cellulose into Glucose.
AB - Mechanochemistry enables enzymatic cleavage of cellulose into glucose without
bulk solvents, acids, other aggressive reagents, or substrate pre-treatment. This
clean mechanoenzymatic process (coined RAging) is also directly applicable to
biomass, avoids many limitations associated with the use of cellulases, and
produces glucose concentrations greater than three times that obtained by
conventional methods.
PMID- 29342317
TI - Osteoblast-like MC3T3-E1 Cells Prefer Glycolysis for ATP Production but Adipocyte
like 3T3-L1 Cells Prefer Oxidative Phosphorylation.
AB - Mesenchymal stromal cells (MSCs) are early progenitors that can differentiate
into osteoblasts, chondrocytes, and adipocytes. We hypothesized that osteoblasts
and adipocytes utilize distinct bioenergetic pathways during MSC differentiation.
To test this hypothesis, we compared the bioenergetic profiles of preosteoblast
MC3T3-E1 cells and calvarial osteoblasts with preadipocyte 3T3L1 cells, before
and after differentiation. Differentiated MC3T3-E1 osteoblasts met adenosine
triphosphate (ATP) demand mainly by glycolysis with minimal reserve glycolytic
capacity, whereas nondifferentiated cells generated ATP through oxidative
phosphorylation. A marked Crabtree effect (acute suppression of respiration by
addition of glucose, observed in both MC3T3-E1 and calvarial osteoblasts) and
smaller mitochondrial membrane potential in the differentiated osteoblasts,
particularly those incubated at high glucose concentrations, indicated a
suppression of oxidative phosphorylation compared with nondifferentiated
osteoblasts. In contrast, both nondifferentiated and differentiated 3T3-L1
adipocytes met ATP demand primarily by oxidative phosphorylation despite a large
unused reserve glycolytic capacity. In sum, we show that nondifferentiated
precursor cells prefer to use oxidative phosphorylation to generate ATP; when
they differentiate to osteoblasts, they gain a strong preference for glycolytic
ATP generation, but when they differentiate to adipocytes, they retain the strong
preference for oxidative phosphorylation. Unique metabolic programming in
mesenchymal progenitor cells may influence cell fate and ultimately determine the
degree of bone formation and/or the development of marrow adiposity. (c) 2018
American Society for Bone and Mineral Research.
PMID- 29342318
TI - Optical Structural Analysis of Individual alpha-Synuclein Oligomers.
AB - Small aggregates of misfolded proteins play a key role in neurodegenerative
disorders. Such species have proved difficult to study due to the lack of
suitable methods capable of resolving these heterogeneous aggregates, which are
smaller than the optical diffraction limit. We demonstrate here an all-optical
fluorescence microscopy method to characterise the structure of individual
protein aggregates based on the fluorescence anisotropy of dyes such as
thioflavin-T, and show that this technology is capable of studying oligomers in
human biofluids such as cerebrospinal fluid. We first investigated in vitro the
structural changes in individual oligomers formed during the aggregation of
recombinant alpha-synuclein. By studying the diffraction-limited aggregates we
directly evaluated their structural conversion and correlated this with the
potential of aggregates to disrupt lipid bilayers. We finally characterised the
structural features of aggregates present in cerebrospinal fluid of Parkinson's
disease patients and age-matched healthy controls.
PMID- 29342319
TI - Validation of The Individualized Neuromuscular Quality of Life in Japanese
patients with myotonic dystrophy.
AB - INTRODUCTION: The Individualized Neuromuscular Quality of Life (INQoL) is used to
measure the quality of life (QoL) of patients with neuromuscular disease. We
conducted this study to translate and validate the Japanese version of the INQoL
in patients with myotonic dystrophy. METHODS: Forward and backward translation,
patient testing, and psychometric validation were performed. We used the 36-Item
Short Form Health Survey (SF-36) and the modified Rankin scale for concurrent
validation. RESULTS: The Japanese INQoL was administered to 90 adult patients.
The coefficients for internal consistency and test-retest reliability were
adequately high in most domains (Cronbach alpha 0.88-0.96 and intraclass
coefficient 0.64-0.99). INQoL domains were moderately to strongly associated with
relevant SF-36 subscales (Spearman's rho -0.23 to -0.74). Symptom severity,
disease duration, employment status, and use of a ventilator influenced overall
QoL. DISCUSSION: The INQoL is a reliable and validated measure of QoL for
Japanese patients with myotonic dystrophy. Muscle Nerve, 2018.
PMID- 29342320
TI - Association of Pre-ESRD Serum Calcium With Post-ESRD Mortality Among Incident
ESRD Patients: A Cohort Study.
AB - Albumin-corrected serum calcium (cSCa) decline at late stages of chronic kidney
disease and rise after dialysis initiation. Although hypercalcemia is associated
with higher mortality in end-stage renal disease (ESRD), there are scarce data on
the impact of pre-ESRD cSCa on post-ESRD mortality. Therefore, we used a large
national cohort of 21,826 US veterans who transitioned to dialysis in all US
Department of Veterans Affairs health care facilities over 2009 to 2014 to
examine the associations with all-cause and cause-specific post-ESRD mortality of
(1) cSCa concentrations averaged over the last 6 months and (2) its rate of
decline during the last 12 months before dialysis initiation. Mean concentrations
and median rate of decline of cSCa were 9.3 +/- 0.7 mg/dL and -0.15
(interquartile range -0.39 to 0.07) mg/dL/year, respectively. A total of 9596
patients died during the follow-up period (mean 1.9 years; total 41,541 patient
years) with an incidence rate of 23.1 per 100 patient-years. There was an
independent linear association between higher cSCa with higher mortality (ptrend
< 0.001). The mortality risk associated with cSCa >=9.0 mg/dL was attenuated
among active vitamin D users (pinteraction < 0.001). Patients with faster decline
in cSCa showed lower mortality irrespective of baseline cSCa concentrations.
These cSCa-mortality associations were stronger for noncardiovascular versus
cardiovascular death. In conclusion, lower pre-ESRD cSCa and faster decline in
cSCa were consistently and linearly associated with better post-ESRD survival
among US veterans, especially for noncardiovascular death. Further studies are
needed to determine if correcting hypocalcemia is beneficial or harmful and which
intervention is preferred when indicated among patients transitioning to ESRD.
(c) 2018 American Society for Bone and Mineral Research.
PMID- 29342322
TI - An Ethenoadenine FAD Analog Accelerates UV Dimer Repair by DNA Photolyase.
PMID- 29342323
TI - Editorial (2018, Issue 1).
PMID- 29342321
TI - Contributions of Material Properties and Structure to Increased Bone Fragility
for a Given Bone Mass in the UCD-T2DM Rat Model of Type 2 Diabetes.
AB - Adults with type 2 diabetes (T2D) have a higher fracture risk for a given bone
quantity, but the mechanisms remain unclear. Using a rat model of polygenic obese
T2D, we demonstrate that diabetes significantly reduces whole-bone strength for a
given bone mass (MUCT-derived BMC), and we quantify the roles of T2D-induced
deficits in material properties versus bone structure; ie, geometry and
microarchitecture. Lumbar vertebrae and ulnae were harvested from 6-month-old
lean Sprague-Dawley rats, obese Sprague-Dawley rats, and diabetic obese UCD-T2DM
rats (diabetic for 69 +/- 7 days; blood glucose >200 mg/dL). Both obese rats and
those with diabetes had reduced whole-bone strength for a given BMC. In obese
rats, this was attributable to structural deficits, whereas in UCD-T2DM rats,
this was attributable to structural deficits and to deficits in tissue material
properties. For the vertebra, deficits in bone structure included thinner and
more rod-like trabeculae; for the ulnae, these deficits included inefficient
distribution of bone mass to resist bending. Deficits in ulnar material
properties in UCD-T2DM rats were associated with increased non-enzymatic
crosslinking and impaired collagen fibril deformation. Specifically, small-angle
X-ray scattering revealed that diabetes reduced collagen fibril ultimate strain
by 40%, and those changes coincided with significant reductions in the elastic,
yield, and ultimate tensile properties of the bone tissue. Importantly, the
biomechanical effects of these material property deficits were substantial.
Prescribing diabetes-specific tissue yield strains in high-resolution finite
element models reduced whole-bone strength by a similar amount (and in some cases
a 3.4-fold greater amount) as the structural deficits. These findings provide
insight into factors that increase bone fragility for a given bone mass in T2D;
not only does diabetes associate with less biomechanically efficient bone
structure, but diabetes also reduces tissue ductility by limiting collagen fibril
deformation, and in doing so, reduces the maximum load capacity of the bone. (c)
2018 American Society for Bone and Mineral Research.
PMID- 29342324
TI - Different Atomic Terminations Affect the Photocatalytic Nitrogen Fixation of
Bismuth Oxybromide: A First Principles Study.
AB - We have systematically investigated the electronic structures and activation
capacities of BiOBr {001} facets with different atomic terminations by means of
DFT methods. Our calculations reveal that oxygen vacancies (OVs) give a
significant boost in band edges of the O-terminated BiOBr {001} facets, and
excess electrons induced by OVs could exceed the reduction potentials of high
energy N2 intermediates. Interestingly, the Bi-terminated BiOBr {001} facets may
be good candidates for photocatalytic nitrogen fixation due to the stronger
activation ability of N2 molecules comparing with O-terminated BiOBr {001} facets
with OVs. Moreover, the Bi-terminated BiOBr {001} facets may tend to yield NH3
instead of N2 H4 .
PMID- 29342325
TI - Neuromuscular complications of immune checkpoint inhibitor therapy.
AB - Immune checkpoint inhibitor (ICPI) therapy unleashes the body's natural immune
system to fight cancer. ICPIs improve overall cancer survival, however, the
unbridling of the immune system may induce a variety of immune-related adverse
events. Neuromuscular immune complications are rare but they can be severe.
Myasthenia gravis and inflammatory neuropathy are the most common neuromuscular
adverse events but a variety of others including inflammatory myopathy are
reported. The pathophysiologic mechanism of these autoimmune disorders may differ
from that of non-ICPI-related immune diseases. Accordingly, while the optimal
treatment for ICPI-related neuromuscular disorders generally follows a
traditional paradigm, there are important novel considerations in selecting
appropriate immunosuppressive therapy. This review presents 2 new cases, a
summary of neuromuscular ICPI complications, and an approach to the diagnosis and
treatment of these disorders. Muscle Nerve, 2018.
PMID- 29342326
TI - Mixed Fluorotryptophan Substitutions at the Same Residue Expand the Versatility
of 19 F Protein NMR Spectroscopy.
AB - The strategy of applying fluorine NMR to characterize ligand binding to a
membrane protein prepared with mixtures of tryptophans substituted with F at
different positions on the indole ring was tested. The 19 F NMR behavior of 4-, 5
, 6-, and 7-fluorotryptophan were directly compared as a function of both
micellar environment and fragment size for two overlapping apelin receptor
(AR/APJ) segments; one with a single transmembrane (TM) helix and two tryptophan
residues, the other with three TM helices and two additional tryptophan residues.
Chemical shifts, peak patterns, and nuclear spin relaxation rates were observed
to vary as a function of micellar conditions and F substitution position in the
indole ring, with the exposure of a given residue to micelle or solvent being the
primary differentiating factor. Titration of the 3-TM AR segment biosynthetically
prepared as a mixture of 5- and 7-fluorotryptophan-containing isoforms by two
distinct peptide ligands (apelin-36 and apela-32) demonstrated site-specific 19 F
peak intensity changes for one ligand but not the other. In contrast, both
ligands perturbed 1 H-15 N HSQC peak patterns to a similar degree.
Characterization of multiple fluorotryptophan types for a given set of tryptophan
residues, thus, significantly augments the potential to apply 19 F NMR to track
otherwise obscure modulation of protein conformation and dynamics without an
explicit requirement for mutagenesis or chemical modification.
PMID- 29342328
TI - Automated measurement of left ventricular ejection fraction and volume using the
Philips EPIQ system: Methodological issues on validity and reproducibility.
PMID- 29342329
TI - When the gold standard is not always golden: The value of invasive hemodynamic
assessment to overcome the pitfalls of echocardiography in challenging cases of
mitral stenosis.
AB - Mitral stenosis is a uncommon valvular lesion in the developed countries.
Noninvasive evaluation is the first-line modality for assessment of mitral
stenosis, however the noninvasive methods may have limitations in certain cases.
Invasive hemodynamics can be used as adjunct tool for assessment of mitral
stenosis in such difficult cases. Mitral valve using three-dimensional planimetry
is a promising technique for assessment of mitral stenosis.
PMID- 29342330
TI - Corrigendum.
PMID- 29342332
TI - ?
PMID- 29342331
TI - Reproducibility of automated measurement of left ventricular volumes and ejection
fraction using the Philips EPIQ system.
PMID- 29342334
TI - ?
PMID- 29342333
TI - ?
PMID- 29342335
TI - ?
PMID- 29342336
TI - ?
PMID- 29342337
TI - ?
PMID- 29342339
TI - ?
PMID- 29342338
TI - ?
PMID- 29342340
TI - ?
PMID- 29342341
TI - Aptamer-Directed Specific Drug Delivery and Magnetic Resonance Imaging of Renal
Carcinoma Cells In Vitro and In Vivo.
AB - Magnetic resonance imaging (MRI) with high spatial resolution has been widely
used in clinics as a noninvasive diagnostic technology, and MRI diagnosis-based
theranostic nanomaterials have attracted increasing attention. Herein, we report
on the fabrication of a GO/BSA-Gd2O3/AS1411-DOX theranostic nanocomplex with BSA
Gd2O3 nanoparticles for use as an MRI contrast agent (CA), with graphene oxide
(GO) nanoplates as the CA and drug nanocarrier, as well as an aptamer, AS1411, as
the targeting molecule. The proposed theranostic nanocomplex not only provided
stronger MR contrast enhancement but also inhibited the growth of 786-0 human
renal carcinoma cells with the help of the AS1411 aptamer, while sparing the
normal cells from harm, thus demonstrating their specific drug delivery
capability. Additionally, 786-0 cells could be specifically recognized using the
GO/BSA-Gd2O3/AS1411-DOX theranostic nanocomplex with MRI both in vitro and in
vivo. Notably, most of the nanocomplex that was injected into the tail vein was
excreted by the kidneys and bladder, while MRI signals from the nanocomplexes
that accumulated specifically in the tumor region could remain as long as 24
hours, which is beneficial for future clinical diagnosis and therapy.
PMID- 29342343
TI - Redox Sensitive Shell and Core Crosslinked Hyaluronic Acid Nanocarriers for Tumor
Targeted Drug Delivery.
AB - The purpose of the present study was to develop a robust and redox-sensitive
nanocarrier based on amphiphilic hyaluronic acid nanoparticles, in which the
hydrophobic core was crosslinked by photo-crosslinking and the hyaluronic acid
shell was crosslinked via a bioreducible disulfide linkage. Dynamic light
scattering showed that the shell and core crosslinked nanocarriers were obviously
more stable than core crosslinked or non-crosslinked nanoparticles. Moreover, the
particle size changed as the glutathione concentration was altered, exhibiting
obvious redox sensitivity. Transmission electron microscopy showed that the
nanoparticle structure was denser after crosslinking. Additionally, methotrexate
was effectively encapsulated into nanoparticles with high drug-loading
efficiency. In vitro methotrexate release assays showed that the methotrexate
loaded bioreducible hyaluronic acid nanoparticles greatly suppressed drug release
in phosphate-buffered saline (pH 7.4) without or with 20 MUM glutathione. In
contrast, in phosphate-buffered saline (pH 7.4) with higher glutathione
concentrations (2, 5, or 10 mM), methotrexate was released more rapidly and
completely from the nanocarriers in 24 h. Furthermore, methotrexate was released
completely and rapidly from the nanoparticles under simulated tumor cell
conditions (pH 5.0 with 10 mM glutathione), suggesting potential applications in
tumor-specific drug release. In vitro anticancer activity tests showed that the
inhibition rate of methotrexate-loaded nanoparticles in HeLa cells reached 94%.
However, excess hyaluronic acid decreased cell toxicity. Cellular uptake studies
suggested that the prepared nanoparticles were probably internalized into the
cancer cells via receptor-mediated endocytosis. Overall, our data demonstrated
that the bio-reducible shell and core crosslinked nanoparticles could be used as
a potential carrier for cancer therapy.
PMID- 29342342
TI - Tranexamic Acid-Encapsulating Thermosensitive Liposomes for Site-Specific
Pharmaco-Laser Therapy of Port Wine Stains.
AB - Site-specific pharmaco-laser therapy (SSPLT) is a developmental stage treatment
modality designed to non-invasively remove superficial vascular pathologies such
as port wine stains (PWS) by combining conventional laser therapy with the prior
administration of a prothrombotic and/or antifibrinolytic pharmaceutical
containing drug delivery system. For the antifibrinolytic SSPLT component, six
different PEGylated thermosensitive liposomal formulations encapsulating
tranexamic acid (TA), a potent antifibrinolytic lysine analogue, were
characterized for drug:lipid ratio, encapsulation efficiency, size, endovesicular
TA concentration (C TA), phase transition temperature (T m), and assayed for heat
induced TA release. Assays were developed for the quantification of liposomal TA
and heat-induced TA release from two candidate formulations. The outcome
parameters were then combined with a 3D histological reconstruction of a port
wine stain biopsy to extrapolate in vivo posologies for SSPLT. The prime
formulation, DPPC:DSPE-PEG2000 (96:4 molar ratio), had a drug:lipid molar ratio
of 0.82, an encapsulation efficiency of 1.29%, a diameter of 155 nm, and a C TA
of 214 mM. The peak TA release from this formulation (T m = 42.3 degrees C)
comprised 96% within 2.5 min, whereas this was 94% in 2 min for DPPC:MPPC:DSPE
PEG2000 (86:10:4) liposomes (T m = 41.5 degrees C). Computational analysis
revealed that < 400 DPPC:DSPE-PEG2000 (96:4 molar ratio) liposomes are needed to
treat a PWS of 40 cm2, compared to a three-fold greater quantity of
DPPC:MPPC:DSPE-PEG2000 (86:10:4) liposomes, indicating that, in light of the
assayed parameters and endovascular laser-tissue interactions, the former
formulation is most suitable for antifibrinolytic SSPLT. This was further
confirmed with experiments involving ex vivo and in vivo liposome-platelet and
liposome-red blood cell association as well as uptake and toxicity assays with
cultured endothelial cells (HUVECs), macrophages (RAW 264.7), and hepatocytes
(HepG2).
PMID- 29342344
TI - A Nanoparticle Carrier for Co-Delivery of Gemcitabine and Small Interfering RNA
in Pancreatic Cancer Therapy.
AB - BACKGROUND: The concept of precision medicine to treat cancer shows promise and a
co-delivery carrier for chemotherapy drugs and target genes is the key tool for
both basic research and clinical application. To address this, we developed a
cancer-targeting nanoparticle vector to transfer gemcitabine (Gem) and small
interfering RNA (siRNA) to pancreatic cancer. METHODS: Iron oxide nanoparticles
(IONPs) resonant at 15 nm were conjugated with the single chain variable fragment
(scFv) against CD44v6 (scFvCD44v6), which has proven pancreatic cancer-targeting
specificity as reported in our previous study. Gem was then linked through a
lysosomally cleavable tetrapeptide linker, resulting in a scFv-targeted
nanoparticle construct, which was subsequently conjugated to siRNA targeting the
Bmi-1 oncogene (siBmi-1) to obtain the multifunctional nanoparticle scFv-Gem
siBmi-1-NPs. A series of biological experiments were performed to test its
biophysical characterization, gene silencing efficacy and anti-tumor effect in
vitro and in vivo. RESULTS: The multifunctional nanoparticle not only possesses
an ultra-small size of approximately 80 nm, excellent biocompatibility and
biodegradability, but also exerts a synergistic anti-tumor effect both in vitro
and in vivo, such as inhibition of tumor cell growth, invasion and migration,
reduction of cell cycle progression and promotion of tumor apoptosis.
Furthermore, this nanoparticle can efficiently target pancreatic cancer in vivo,
resulting in the enhanced bioavailability and efficacy of Gem. CONCLUSION: scFv
Gem-siBmi-1-NPs provide an effective and targeted co-delivery of Gem and siBmi-1
to pancreatic cancer, and exert an efficient and corporate anti-tumor therapeutic
effect. This prospective vector shows promise for precise treatment of pancreatic
cancer.
PMID- 29342345
TI - Comprehensive Analysis of Secreted Protein, Acidic and Rich in Cysteine in
Prostate Carcinogenesis: Development of a 3D Nanostructured Bone-Like Model.
AB - Most aggressive prostate cancer (PCa) types tend to metastasize frequently to
bone and SPARC, a matricellular protein, might participate in such biological
processes. The objective of this study was to evaluate the effect of SPARC in
prostate carcinogenesis and bone metastization. This was explored assessing the
morphology, metabolic activity and SPARC expression of different PCa cell lines
resembling different stages of carcinogenesis, using a 3D bone-biomimetic model
(collagen nanofibers/nanohydroxyapatite) grafted with SPARC. Our findings
highlight distinct cellular behavior depending on cell type and presence of
exogenous SPARC. In fact, SPARC addition contributed to the survival and
significant growth of a non-bone metastatic PCa cell line (LNCaP) on bone-like
biomaterial. Moreover, SPARC expression levels were evaluated in a series of
prostatic tissues, comparing normal prostate, pre-neoplastic prostate
intraepithelial neoplasias and overtly malignant tumors, and also metastasis to
its correspondent primary prostate tumors, ascertaining potential association
between SPARC and clinicopathological data. Remarkably, SPARC was overexpressed
in patients with higher Gleason Score, indicating tumors with poor prognosis, as
well as in metastasis, particularly from bone sites, compared with their
respective primary tumors. The results suggest a potential role of SPARC as a
clinical target on PCa, due to its association with bone metastization.
PMID- 29342346
TI - Ratiometric Reactive Oxygen Species Nanoprobe for Noninvasive In Vivo Imaging of
Subcutaneous Inflammation/Infection.
AB - Release of reactive oxygen species (ROS) accompanied with acute inflammation and
infection often results in cell death and tissue injury. Several ROS-reactive
bioluminescent probes have been investigated in recent years to detect ROS
activity in vivo. Unfortunately, these probes cannot be used to quantify the
degree of ROS activity and inflammatory responses due to the fact that the extent
of the bioluminescent signals is also probe-concentration dependent. To address
this challenge, we fabricated a ratiometric ROS probe in which both ROS-sensitive
chemiluminescent agents and ROS-insensitive fluorescent reference dye were
conjugated to particle carriers. The bioluminescence/reference fluorescence
intensity ratios was calculated to reflect the extent of localized ROS activities
while circumventing the variations in bioluminescent intensities associated with
the ROS probe concentrations. The physical and chemical properties of the
ratiometric probes were characterized. Furthermore, we assessed the accuracy and
reproducibility of the probe in detecting ROS in vitro. The ability of the
ratiometric probes to detect ROS production in inflamed/infected tissues was also
examined using animal models of inflammation and infection. The overall results
imply that ratiometric ROS probes can rapidly and non-invasively detect and
quantify the extent of inflammatory responses and bacterial infection on wounds
in real time.
PMID- 29342347
TI - A pH-Sensitive Nanosystem Based on Carboxymethyl Chitosan for Tumor-Targeted
Delivery of Daunorubicin.
AB - Nanoparticles, such as polymeric micelles, are currently regarded as effective
drug delivery vehicles. In this study, a series of carboxymethyl
chitosan/daunorubicin (CMCS/DNR) conjugates with macromolecular carriers of
different molecular weights (MWs) were prepared and structurally characterized by
Fourier transform infrared spectroscopy (FT-IR) and 1H-NMR spectroscopy. The
results indicated that the MWs of the carriers greatly influenced the drug
loading capacity. DNR was conjugated to the polymer via an acid-sensitive
hydrazone linkage susceptible to hydrolysis at pH 5-6, thereby enabling
intracellular DNR release. In aqueous media, the conjugates spontaneously formed
nano-sized particles with core-shell structures (CMCS and DNR as the shell and
core, respectively). Dynamic light scattering (DLS) and trans-mission electron
microscopy (TEM) indicated that the prepared nanoparticles were spherical in
shape with diameters of 100-200 nm and had a slight negative surface charge. In
addition, in vitro drug release studies demonstrated that the micelles were
highly sensitive to mild acidic conditions (pH 5.0) but remained reasonably
stable at pH 6.5 and pH 7.4. Importantly, cell counting kit-8 (CCK-8) assays
demonstrated that DNR-conjugated nanoparticles exerted a cytotoxic effect on HeLa
cells, with the IC50 being approximately 2 times higher than that of free-DNR.
Furthermore, confocal laser scanning microscopy (CLSM) revealed that the CMCS-hyd
DNR nanosystem could efficiently deliver and release DNR in the nuclei of cancer
cells. Taken together, the developed CMCS based pH-sensitive nanosystem may be a
potential drug delivery vehicle for cancer therapy.
PMID- 29342348
TI - Characterization of the Uptake Efficiency and Cytotoxicity of Tetrandrine-Loaded
Poly(N-vinylpyrrolidone)-Block-Poly(epsilon-caprolactone) (PVP-b-PCL)
Nanoparticles in the A549 Lung Adenocarcinoma Cell Line.
AB - Tetrandrine (Tet) has been previously reported to induce apoptosis in several
cancer cell lines. However, poor Tet solubility has limited its further
application. The lipophilicity of Tet suggests that the development of Tet-loaded
biodegradable polymeric micelle delivery systems may be possible. In our previous
work, we demonstrated the superior antitumor efficiency of Tet-loaded mPEG-PCL
nanoparticles (NPs) in colorectal cancer cell lines. In the present study, we
report that a spherical core-shell Tet-loaded nanoparticle structure was prepared
using a nanoprecipitation method by employing amphiphilic poly(N
vinylpyrrolidone)-block-poly(epsilon-caprolactone) (PVP-b-PCL) copolymers as drug
carriers. Tet was incorporated into the NPs with high encapsulation efficiency
and released in a sustained release pattern. Moreover, coumarin-6 (hydrophobic
fluorescence)-loaded Tet-NP uptake was shown to be mediated mainly by endocytosis
from the NPs and was more efficient than that of rhodamine B (hydrophilic
fluorescence)-loaded NP uptake, which was mainly dependent upon infiltration. The
endocytic uptake process was blocked by NaN3, a mitochondrial inhibitor. In vitro
studies using the A549 cell line demonstrated the superior cytotoxicity and
apoptosis induction ability of Tet-NPs in dose- and time-dependent manners
compared to free Tet. The data obtained from this study, therefore, not only
confirm the potential use of Tet to treat lung cancer but also suggest an
effective manner by which to improve the anticancer efficiency of Tet in nano
drug delivery systems.
PMID- 29342350
TI - Real-Time Monitoring of Chemical Changes in Three Kinds of Fermented Milk
Products during Fermentation Using Quantitative Difference Nuclear Magnetic
Resonance Spectroscopy.
AB - Fermented milk products are rising in popularity throughout the world as a result
of their health benefits, including improving digestion, normalizing the function
of the immune system, and aiding in weight management. This study applies an in
situ quantitative nuclear magnetic resonance method to monitor chemical changes
in three kinds of fermented milk products, Bulgarian yogurt, Caspian Sea yogurt,
and kefir, during fermentation. As a result, the concentration changes in nine
organic compounds, alpha/beta-lactose, alpha/beta-galactose, lactic acid,
citrate, ethanol, lecithin, and creatine, were monitored in real time. This
revealed three distinct metabolic processes in the three fermented milk products.
Moreover, pH changes were also determined by variations in the chemical shift of
citric acid during the fermentation processes. These results can be applied to
estimate microbial metabolism in various flora and help guide the fermentation
and storage of various fermented milk products to improve their quality, which
may directly influence human health.
PMID- 29342349
TI - Membrane Allostery and Unique Hydrophobic Sites Promote Enzyme Substrate
Specificity.
AB - We demonstrate that lipidomics coupled with molecular dynamics reveal unique
phospholipase A2 specificity toward membrane phospholipid substrates. We
discovered unexpected headgroup and acyl-chain specificity for three major human
phospholipases A2. The differences between each enzyme's specificity, coupled
with molecular dynamics-based structural and binding studies, revealed unique
binding sites and interfacial surface binding moieties for each enzyme that
explain the observed specificity at a hitherto inaccessible structural level.
Surprisingly, we discovered that a unique hydrophobic binding site for the
cleaved fatty acid dominates each enzyme's specificity rather than its catalytic
residues and polar headgroup binding site. Molecular dynamics simulations
revealed the optimal phospholipid binding mode leading to a detailed
understanding of the preference of cytosolic phospholipase A2 for cleavage of
proinflammatory arachidonic acid, calcium-independent phospholipase A2, which is
involved in membrane remodeling for cleavage of linoleic acid and for
antibacterial secreted phospholipase A2 favoring linoleic acid, saturated fatty
acids, and phosphatidylglycerol.
PMID- 29342351
TI - Organic Mixed Valence Compounds Derived from Cyclic (Alkyl)(amino)carbenes.
AB - Readily available room temperature stable organic mixed valence compounds are
prepared by one-electron reduction of cyclic bis(iminium) salts [derived from
cyclic (alkyl)(amino)carbenes] bridged by various spacers. These compounds show
characteristic intervalence charge transfer (IV-CT) bands in the near-infrared
(NIR). Cyclic voltammetry, EPR, IR, UV-vis, and X-ray studies, as well as DFT
calculations, show that, depending on the nature of the spacer, these mixed
valence compounds range from class III to class II.
PMID- 29342353
TI - Synthesis and Computational Studies Demonstrate the Utility of an Intramolecular
Styryl Diels-Alder Reaction and Di-t-butylhydroxytoluene Assisted [1,3]-Shift to
Construct Anticancer dl-Deoxypodophyllotoxin.
AB - Deoxypodophyllotoxin is a secondary metabolite lignan possessing potent
anticancer activity with potential as a precursor for known anticancer drugs, but
its use is limited by scarcity from natural sources. We here report the total
synthesis of racemic deoxypodophyllotoxin in seven steps using an intramolecular
styryl Diels-Alder reaction strategy uniquely suited to assemble the
deoxypodophyllotoxin core. Density functional theory was used to analyze
concerted, polar, and singlet-open-shell diradical reaction pathways, which
identified a low-energy concerted [4 + 2] Diels-Alder pathway followed by a
faster di-t-butylhydroxytoluene assisted [1,3]-formal hydrogen shift.
PMID- 29342354
TI - A Highly Dynamic Loop of the Pseudomonas aeruginosa PA14 Type IV Pilin Is
Essential for Pilus Assembly.
AB - Type IVa pili (T4aP) are long, thin surface filaments involved in attachment,
motility, biofilm formation, and DNA uptake. They are important virulence factors
for many bacteria, including Pseudomonas aeruginosa, an opportunistic pathogen
and common cause of hospital-acquired infections. Each helical filament contains
thousands of monomers of the major pilin subunit, PilA. Each P. aeruginosa strain
expresses one of five phylogenetically distinct major pilins, which vary in
sequence and the nature of their associated accessory protein(s). Here, we
present the backbone resonance assignment of the C-terminal domain of the group
III PilA from strain PA14, a highly virulent, globally distributed clone.
Secondary structure probabilities calculated from chemical shifts were in
excellent agreement with previous homology modeling using a group V pilin
structural template. The analysis revealed that the distal segment of the
alphabeta loop had high microsecond-millisecond dynamics compared with other loop
regions. Shortening of this segment by internal deletion abrogated pilus assembly
in a dominant negative manner, suggesting a potential role in pilin
polymerization. Pilin conformations that support optimal interactions of both the
conserved hydrophobic N-termini in the pilus core and hydrophilic loops creating
the filament surface may be necessary to produce stable filaments.
PMID- 29342352
TI - Chemically Defined Antibody- and Small Molecule-Drug Conjugates for in Vivo Tumor
Targeting Applications: A Comparative Analysis.
AB - We present the first direct comparative evaluation of an antibody-drug conjugate
and of a small molecule-drug conjugate for cancer therapy, using chemically
defined products which bind with high-affinity to carbonic anhydrase IX, a marker
of tumor hypoxia and of renal cell carcinoma.
PMID- 29342355
TI - Convergence of Kirkwood-Buff Integrals of Ideal and Nonideal Aqueous Solutions
Using Molecular Dynamics Simulations.
AB - The computation of Kirkwood-Buff integrals (KBIs) using molecular simulations of
closed systems is challenging due to finite system-size effects. One of the
problems involves the incorrect asymptotic behavior of the radial distribution
function. Corrections to rectify such effects have been proposed in the
literature. This study reports a systematic comparison of the proposed
corrections (as given by Ganguly et al. J. Chem. Theory Comput. 2013, 9, 1347
1355 and Kruger et al. J. Phys. Chem. Lett. 2013, 4, 4-7) to assess the
asymptotic behavior of the RDFs, the KBIs, as well as the estimation of
thermodynamic quantities for ideal urea-water and nonideal modified-urea-water
mixtures using molecular dynamics simulations. The results show that applying the
KBI correction suggested by Kruger et al. on the RDF corrected with the Ganguly
et al. correction (denoted as B-KBI) yields improved KBI convergence for the
ideal and nonideal aqueous mixtures. Different averaging regions in the running
KBIs (correlated or long-range) are assessed, and averaging over the correlated
region for large system sizes is found to be robust toward the change in the
degree of solvent nonideality and concentration, providing good estimates of
thermodynamic quantities. The study provides new insights into improving the KBI
convergence, the suitability of different averaging regions in KBIs to estimate
thermodynamic properties, as well as the applicability of correction methods to
achieve KBI convergence for nonideal aqueous binary mixtures.
PMID- 29342356
TI - The DARK Side of Total Synthesis: Strategies and Tactics in Psychoactive Drug
Production.
AB - Humankind has used and abused psychoactive drugs for millennia. Formally, a
psychoactive drug is any agent that alters cognition and mood. The term
"psychotropic drug" is neutral and describes the entire class of substrates,
licit and illicit, of interest to governmental drug policy. While these drugs are
prescribed for issues ranging from pain management to anxiety, they are also used
recreationally. In fact, the current opioid epidemic is the deadliest drug crisis
in American history. While the topic is highly politicized with racial, gender,
and socioeconomic elements, there is no denying the toll drug mis- and overuse is
taking on this country. Overdose, fueled by opioids, is the leading cause of
death for Americans under 50 years of age, killing ca. 64,000 people in 2016.
From a chemistry standpoint, the question is in what ways, if any, did organic
chemists contribute to this problem? In this targeted review, we provide brief
historical accounts of the main classes of psychoactive drugs and discuss several
foundational total syntheses that ultimately provide the groundwork for producing
these molecules in academic, industrial, and clandestine settings.
PMID- 29342357
TI - Diffusion-Controlled Epitaxy of Large Area Coalesced WSe2 Monolayers on Sapphire.
AB - A multistep diffusion-mediated process was developed to control the nucleation
density, size, and lateral growth rate of WSe2 domains on c-plane sapphire for
the epitaxial growth of large area monolayer films by gas source chemical vapor
deposition (CVD). The process consists of an initial nucleation step followed by
an annealing period in H2Se to promote surface diffusion of tungsten-containing
species to form oriented WSe2 islands with uniform size and controlled density.
The growth conditions were then adjusted to suppress further nucleation and
laterally grow the WSe2 islands to form a fully coalesced monolayer film in less
than 1 h. Postgrowth structural characterization demonstrates that the WSe2
monolayers are single crystal and epitaxially oriented with respect to the
sapphire and contain antiphase grain boundaries due to coalescence of 0 degrees
and 60 degrees oriented WSe2 domains. The process also provides fundamental
insights into the two-dimensional (2D) growth mechanism. For example, the
evolution of domain size and cluster density with annealing time follows a 2D
ripening process, enabling an estimate of the tungsten-species surface
diffusivity. The lateral growth rate of domains was found to be relatively
independent of substrate temperature over the range of 700-900 degrees C
suggesting a mass transport limited process, however, the domain shape
(triangular versus truncated triangular) varied with temperature over this same
range due to local variations in the Se/W adatom ratio. The results provide an
important step toward atomic level control of the epitaxial growth of WSe2
monolayers in a scalable process that is suitable for large area device
fabrication.
PMID- 29342358
TI - Synthesis and Biological Characterization of Aryl Uracil Inhibitors of Hepatitis
C Virus NS5B Polymerase: Discovery of ABT-072, a trans-Stilbene Analog with Good
Oral Bioavailability.
AB - ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as
part of a program to identify new direct-acting antivirals (DAAs) for the
treatment of HCV infection. This compound was identified during a medicinal
chemistry effort to improve on an original lead, inhibitor 1, which we described
in a previous publication. Replacement of the amide linkage in 1 with a trans
olefin resulted in improved compound permeability and solubility and provided
much better pharmacokinetic properties in preclinical species. Replacement of the
dihydrouracil in 1 with an N-linked uracil provided better potency in the
genotype 1 replicon assay. Results from phase 1 clinical studies supported once
daily oral dosing with ABT-072 in HCV infected patients. A phase 2 clinical study
that combined ABT-072 with the HCV protease inhibitor ABT-450 provided a
sustained virologic response at 24 weeks after dosing (SVR24) in 10 of 11
patients who received treatment.
PMID- 29342359
TI - Semiconducting Photothermal Nanoagonist for Remote-Controlled Specific Cancer
Therapy.
AB - Nanomedicine have shown success in cancer therapy, but the pharmacological
actions of most nanomedicine are often nonspecific to cancer cells because of
utilization of the therapeutic agents that induce cell apoptosis from inner
organelles. We herein report the development of semiconducting photothermal
nanoagonists that can remotely and specifically initiate the apoptosis of cancer
cells from cell membrane. The organic nanoagonists comprise semiconducting
polymer nanoparticles (SPNs) and capsaicin (Cap) as the photothermally responsive
nanocarrier and the agonist for activation of transient receptor potential cation
channel subfamily V member 1 (TRPV1), respectively. Under multiple NIR laser
irradiation at the time scale of seconds, the nanoagonists can repeatedly and
locally release Cap to multiply activate TRPV1 channels on the cellular membrane;
the cumulative effect is the overinflux of ions in mitochondria followed by the
induction of cell apoptosis specifically for TRPV1-postive cancer cells. Multiple
transient activation of TRPV1 channels is essential to induce such a cell death
both in vitro and in vivo because both free Cap and simple Cap-encapsulated
nanoparticles fail to do so. The photothermally triggered release also ensures a
high local concentration of the TRPV1 agonist at tumor site, permitting specific
cancer cell therapy at a low systemic administration dosage. Our study thus
demonstrates the first example of ion-channel-specific and remote-controlled drug
delivery system for cancer cell therapy.
PMID- 29342361
TI - High-Speed Spectroscopic Transient Absorption Imaging of Defects in Graphene.
AB - Graphene grain boundaries (GBs) and other nanodefects can deteriorate electronic
properties. Here, using transient absorption (TA) microscopy we directly
visualized GBs by TA intensity increase due to change in density of state. We
also observed a faster decay due to defect-accelerated carrier relaxation in the
GB area. By line-illumination and parallel detection, we increased the TA
intensity imaging speed to 1000 frames per second, which is 6 orders of magnitude
faster than Raman microscopy. Combined with a resonant optical delay tuner which
scans a 5.3 ps temporal delay within 92 MUs, our system enabled spectroscopic TA
imaging, at a speed of 50 stacks per second, to probe and characterize graphene
nanodefects based on the TA decay rate. Finally, we demonstrate real-time
nondestructive characterization of graphene at a rolling speed of 0.3 m/min,
which matches the fastest roll-to-roll manufacturing process reported.
PMID- 29342360
TI - Sustained Delivery of Doxorubicin via Acetalated Dextran Scaffold Prevents
Glioblastoma Recurrence after Surgical Resection.
AB - The primary cause of mortality for glioblastoma (GBM) is local tumor recurrence
following standard-of-care therapies, including surgical resection. With most
tumors recurring near the site of surgical resection, local delivery of
chemotherapy at the time of surgery is a promising strategy. Herein drug-loaded
polymer scaffolds with two distinct degradation profiles were fabricated to
investigate the effect of local drug delivery rate on GBM recurrence following
surgical resection. The novel biopolymer, acetalated dextran (Ace-DEX), was
compared with commercially available polyester, poly(l-lactide) (PLA). Steady
state doxorubicin (DXR) release from Ace-DEX scaffolds was found to be faster
when compared with scaffolds composed of PLA, in vitro. This increased drug
release rate translated to improved therapeutic outcomes in a novel surgical
model of orthotopic glioblastoma resection and recurrence. Mice treated with DXR
loaded Ace-DEX scaffolds (Ace-DEX/10DXR) resulted in 57% long-term survival out
to study completion at 120 days compared with 20% survival following treatment
with DXR-loaded PLA scaffolds (PLA/10DXR). Additionally, all mice treated with
PLA/10DXR scaffolds exhibited disease progression by day 38, as defined by a 5
fold growth in tumor bioluminescent signal. In contrast, 57% of mice treated with
Ace-DEX/10DXR scaffolds displayed a reduction in tumor burden, with 43%
exhibiting complete remission. These results underscore the importance of polymer
choice and drug release rate when evaluating local drug delivery strategies to
improve prognosis for GBM patients undergoing tumor resection.
PMID- 29342362
TI - Stereospecific Syntheses of Enaminonitriles and beta-Enaminoesters via Domino
Ring-Opening Cyclization (DROC) of Activated Cyclopropanes with Pronucleophilic
Malononitriles.
AB - Two novel synthetic protocols for the syntheses of highly functionalized five
membered carbocyclic enaminonitriles and beta-enaminoesters have been developed
via domino ring-opening cyclization (DROC) and DROC/decarboxylative
tautomerization of activated cyclopropanes with malononitrile pronucleophiles,
respectively. Both of the efficient strategies (yield up to 93%) have been
generalized with various donor-acceptor and acceptor cyclopropanes as well as
with malononitrile derivatives. The stereospecific variants of the two SN2-type
DROC strategies have also been developed by employing enantiopure donor-acceptor
(DA) cyclopropanes to synthesize the corresponding nonracemic products with
excellent stereoselectivities (dr up to >99:1, ee up to >99%).
PMID- 29342365
TI - A Standardized Diagnostic Ontology for Fibrotic Interstitial Lung Disease.
PMID- 29342363
TI - Differential effects of inhibitory G protein isoforms on G protein-gated inwardly
rectifying K+ currents in adult murine atria.
AB - G protein-gated inwardly rectifying K+ (GIRK) channels are the major inwardly
rectifying K+ currents in cardiac atrial myocytes and an important determinant of
atrial electrophysiology. Inhibitory G protein alpha-subunits can both mediate
activation via acetylcholine but can also suppress basal currents in the absence
of agonist. We studied this phenomenon using whole cell patch clamping in murine
atria from mice with global genetic deletion of Galphai2, combined deletion of
Galphai1/Galphai3, and littermate controls. We found that mice with deletion of
Galphai2 had increased basal and agonist-activated currents, particularly in the
right atria while in contrast those with Galphai1/Galphai3 deletion had reduced
currents. Mice with global genetic deletion of Galphai2 had decreased action
potential duration. Tissue preparations of the left atria studied with a
multielectrode array from Galphai2 knockout mice showed a shorter effective
refractory period, with no change in conduction velocity, than littermate
controls. Transcriptional studies revealed increased expression of GIRK channel
subunit genes in Galphai2 knockout mice. Thus different G protein isoforms have
differential effects on GIRK channel behavior and paradoxically Galphai2 act to
increase basal and agonist-activated GIRK currents. Deletion of Galphai2 is
potentially proarrhythmic in the atria.
PMID- 29342364
TI - Influence of knee joint position and sex on vastus medialis regional
architecture.
AB - Ultrasound imaging was used to investigate vastus medialis (VM) architecture in
10 males and 10 females at different knee angles. Increase in muscle thickness
occurs predominantly when the knee angle is changed from 0 degrees (full
extension) and 45 degrees (p < 0.05); increases in VM pennation angle can be
predominantly observed between 45 degrees and 90 degrees (p < 0.05). Sex
differences in the VM architecture can be observed in the distal (p < 0.01) but
not in the proximal region of the muscle (p > 0.11).
PMID- 29342366
TI - Evaluation of the Get Active Questionnaire in community-dwelling older adults.
AB - Physical activity screening prior to starting a physical activity program is
important to identify if there are any underlying health conditions. However,
many older adults do not complete such assessments prior to beginning their
physical activity program. This project compared the Canadian Society for
Exercise Physiology's newly developed Get Active Questionnaire (GAQ) to a
standardized exercise stress test in terms of screening out versus screening in
false-positive GAQ tests. A convenience sample of community-dwelling adults (male
n = 58, female n = 54) aged 75 +/- 7 years from London, Ontario, Canada, was
used. Participants completed a physical exam and physical activity screening
session (i.e., stress test and GAQ) at a research laboratory that routinely
conducts community-based referrals. One week after the initial visit,
participants returned to the study site, completed the GAQ, and were asked
questions about their perceptions of physical activity screening by a research
assistant. The GAQ "screened in" participants, but it did not provide the same
precision of "screening out" at-risk individuals as an exercise stress test; the
GAQ reduced false-positives versus the stress test, yet there was a large
proportion of high false-negative results reported. The GAQ shows promise in
physical activity screening in older adults to engage in exercise safely.
However, the lack of precision in physical-activity screening out of at-risk
populations requires further evaluation. Questionnaires such as the GAQ should be
evaluated in a larger study population at various time points to further assess
the validity and reliability of physical activity screening tools.
PMID- 29342367
TI - Cystic Fibrosis Foundation Pulmonary Guidelines. Use of Cystic Fibrosis
Transmembrane Conductance Regulator Modulator Therapy in Patients with Cystic
Fibrosis.
AB - RATIONALE: Cystic fibrosis (CF) transmembrane conductance regulator (CFTR)
modulators are a new class of medications targeting the underlying defect in CF.
Ivacaftor (IVA) and IVA combined with lumacaftor (LUM; IVA/LUM) have been
approved by the U.S. Food and Drug Administration (FDA) for use in patients with
CF. However, the FDA label for these medications encompasses patient groups that
were not studied as part of the drug approval process. CF clinicians, patients,
and their families have recognized a need for recommendations to guide the use of
these medications. OBJECTIVE: Develop evidence-based guidelines for CFTR
modulator therapy in patients with CF. METHODS: A multidisciplinary committee of
CF caregivers and patient representatives was assembled. A methodologist, an
epidemiologist, a medical librarian, and a biostatistician were recruited to
assist with the literature search, evidence grading, and generation of
recommendations. The committee developed clinical questions using the Patient
Intervention-Comparison-Outcome format. A systematic review was conducted to find
relevant publications. The evidence was then evaluated using the GRADE (Grading
of Recommendations, Assessment, Development, and Evaluation) approach, and
recommendations were made based on this analysis. RESULTS: For adults and
children aged 6 years and older with CF due to gating mutations other than G551D
or R117H, the guideline panel made a conditional recommendation for treatment
with IVA. For those with the R117H mutation, the guideline panel made a
conditional recommendation for treatment with IVA for 1) adults aged 18 years or
older, and 2) children aged 6-17 years with a forced expiratory volume in 1
second (FEV1) less than 90% predicted. For those with the R117H mutation, the
guideline panel made a conditional recommendation against treatment with IVA for
1) children aged 12-17 years with an FEV1 greater than 90% predicted, and 2)
children less than 6 years of age. Among those with two copies of F508del, the
guideline panel made a strong recommendation for treatment with IVA/LUM for
adults and children aged 12 years and older with an FEV1 less than 90% predicted;
and made a conditional recommendation for treatment with IVA/LUM for 1) adults
and children aged 12 years or older with an FEV1 greater than 90% predicted, and
2) children aged 6-11 years. CONCLUSIONS: Using the GRADE approach, we have made
recommendations for the use of CFTR modulators in patients with CF. These
recommendations will be of help to CF clinicians, patients, and their families in
guiding decisions regarding use of these medications.
PMID- 29342368
TI - Reply to Moodley: A Standardized Diagnostic Ontology for Fibrotic Interstitial
Lung Disease.
PMID- 29342369
TI - Added Sugar Consumption and Chronic Oral Disease Burden among Adolescents in
Brazil.
AB - Chronic oral diseases are rarely studied together, especially with an emphasis on
their common risk factors. This study examined the association of added sugar
consumption on "chronic oral disease burden" among adolescents, with
consideration of obesity and systemic inflammation pathways through structural
equation modeling. A cross-sectional study was conducted of a complex random
sample of adolescent students enrolled at public schools in Sao Luis, Brazil ( n
= 405). The outcome was chronic oral disease burden, a latent variable based on
the presence of probing depth >=4 mm, bleeding on probing, caries, and clinical
consequences of untreated caries. The following hypotheses were tested: 1) caries
and periodontal diseases among adolescents are correlated with each other; 2)
added sugar consumption and obesity are associated with chronic oral disease
burden; and 3) chronic oral disease burden is linked to systemic inflammation.
Models were adjusted for socioeconomic status, added sugar consumption, oral
hygiene behaviors, obesity, and serum levels of interleukin 6 (IL-6). All
estimators of the latent variable chronic oral disease burden involved factor
loadings >=0.5 and P values <0.001, indicating good fit. Added sugar consumption
(standardized coefficient [SC] = 0.212, P = 0.005), high IL-6 levels (SC = 0.130,
P = 0.036), and low socioeconomic status (SC = -0.279, P = 0.001) were associated
with increased chronic oral disease burden values. Obesity was associated with
high IL-6 levels (SC = 0.232, P = 0.001). Visible plaque index was correlated
with chronic oral disease burden (SC = 0.381, P < 0.001). Our finding that caries
and periodontal diseases are associated with each other and with added sugar
consumption, obesity, and systemic inflammation reinforces the guidance of the
World Health Organization that any approach intended to prevent noncommunicable
diseases should be directed toward common risk factors.
PMID- 29342371
TI - Global-, Regional-, and Country-Level Economic Impacts of Dental Diseases in
2015.
AB - Up-to-date information about the economic impact of dental diseases is essential
for health care decision makers when seeking to make rational use of available
resources. The purpose of this study was to provide up-to-date estimates for
dental expenditures (direct costs) and productivity losses (indirect costs) due
to dental diseases on the global, regional, and country level. Direct costs of
dental diseases were estimated using a previously established systematic
approach; indirect costs were estimated using an approach developed by the World
Health Organization Commission on Macroeconomics and Health and factoring in 2015
values for gross domestic product and disability-adjusted life years from the
Global Burden of Disease Study. The estimated direct costs of dental diseases
amounted to $356.80 billion and indirect costs were estimated at $187.61 billion,
totaling worldwide costs due to dental diseases of $544.41 billion in 2015. After
adjustment for purchasing power parity, the highest levels of per capita dental
expenditures were found for High-Income North America, Australasia, Western
Europe, High-Income Asia Pacific, and East Asia; the highest levels of per capita
productivity losses were found for Western Europe, Australasia, High-Income North
America, High-Income Asia Pacific, and Central Europe. Severe tooth loss was
found to imply 67% of global productivity losses due to dental diseases, followed
by severe periodontitis (21%) and untreated caries (12%). From an economic
perspective, improvements in population oral health may be highly beneficial and
could contribute to further increases in people's well-being given available
resources.
PMID- 29342370
TI - FGF8 Signaling Alters the Osteogenic Cell Fate in the Hard Palate.
AB - Fibroblast growth factor (FGF) signaling has been implicated in the regulation of
osteogenesis in both intramembranous and endochondral ossifications. In the
developing palate, the anterior bony palate forms by direct differentiation of
cranial neural crest (CNC)-derived mesenchymal cells, but the signals that
regulate the osteogenic cell fate in the developing palate remain unclear. In the
present study, we investigated the potential role of FGF signaling in osteogenic
fate determination of the palatal mesenchymal cells. We showed that locally
activated FGF8 signaling in the anterior palate using a Shox2Cre knock-in allele
and an R26RFgf8 allele leads to a unique palatal defect: a complete loss of the
palatine process of the maxilla as well as formation of ectopic cartilaginous
tissues in the anterior palate. This aberrant developmental process was
accompanied by a significantly elevated level of cell proliferation, which
contributes to an abnormally thickened palatal tissue, where the palatine process
of the maxilla would normally form, and by a complete inhibition of Osterix
expression, which accounts for the lack of bone formation. The coexpression of
Runx2 initially with Sox9 and subsequently with Col II in the ectopic
cartilaginous tissues indicates a conversion of osteogenic fate to a chondrogenic
one. Consistent with the unique palatal phenotype, RNA-Sequencing analysis
revealed that the augmented FGF8 signaling downregulated genes involved in
ossification, biomineral tissue development, and bone mineralization but
upregulated genes involved in cell proliferation, cartilage development, and cell
fate commitment, which was further supported by quantitative real-time reverse
transcription polymerase chain reaction validation of selected genes. Our results
demonstrate that FGF8 signaling functions as a negative regulator of osteogenic
fate and is sufficient to convert a subset of CNC cell-derived mesenchymal cells
into cartilage in the anterior hard palate, which will have implications in
future directed differentiation of CNC-derived precursor cells for clinical
application.
PMID- 29342373
TI - Errata.
PMID- 29342374
TI - Errata.
PMID- 29342372
TI - Enrichment of antibiotic resistance genes in soil receiving composts derived from
swine manure, yard wastes, or food wastes, and evidence for multiyear persistence
of swine Clostridium spp.
AB - The impact of amendment with swine manure compost (SMC), yard waste compost
(YWC), or food waste compost (FWC) on the abundance of antibiotic resistance
genes in soil was evaluated. Following a commercial-scale application of the
composts in a field experiment, soils were sampled periodically for a decade, and
archived air-dried. Soil DNA was extracted and gene targets quantified by qPCR.
Compared with untreated control soil, all 3 amendment types increased the
abundance of gene targets for up to 4 years postapplication. The abundance of
several gene targets was much higher in soil amended with SMC than in soil
receiving either YWC or FWC. The gene target ermB remained higher in the SMC
treatment for a decade postapplication. Clostridia were significantly more
abundant in the SMC-amended soil throughout the decade following application.
Eight percent of Clostridium spp. isolates from the SMC treatment carried ermB.
Overall, addition of organic amendments to soils has the potential to increase
the abundance of antibiotic resistance genes. Amendments of fecal origin, such as
SMC, will in addition entrain bacteria carrying antibiotic resistance genes.
Environmentally recalcitrant clostridia, and the antibiotic resistance genes that
they carry, will persist for many years under field conditions following the
application of SMC.
PMID- 29342375
TI - Errata.
PMID- 29342376
TI - Countering HIV - Three's the Charm?
PMID- 29342377
TI - Bivalirudin versus Heparin Monotherapy in Myocardial Infarction.
PMID- 29342378
TI - In the Balance.
PMID- 29342379
TI - Elimination of Cost Sharing for Screening Mammography in Medicare Advantage
Plans.
AB - BACKGROUND: The Affordable Care Act (ACA) required most insurers and the Medicare
program to eliminate cost sharing for screening mammography. METHODS: We
conducted a difference-in-differences study of biennial screening mammography
among 15,085 women 65 to 74 years of age in 24 Medicare Advantage plans that
eliminated cost sharing to provide full coverage for screening mammography, as
compared with 52,035 women in 48 matched control plans that had and maintained
full coverage. RESULTS: In plans that eliminated cost sharing, adjusted rates of
biennial screening mammography increased from 59.9% (95% confidence interval
[CI], 54.9 to 65.0) in the 2-year period before cost-sharing elimination to 65.4%
(95% CI, 61.8 to 69.0) in the 2-year period thereafter. In control plans, the
rates of biennial mammography were 73.1% (95% CI, 69.2 to 77.0) and 72.8% (95%
CI, 69.7 to 76.0) during the same periods, yielding a difference in differences
of 5.7 percentage points (95% CI, 3.0 to 8.4). The difference in differences was
9.8 percentage points (95% CI, 4.5 to 15.2) among women living in the areas with
the highest quartile of educational attainment versus 4.3 percentage points (95%
CI, 0.2 to 8.4) among women in the lowest quartile. As indicated by the
difference-in-differences estimates, after the elimination of cost sharing, the
rate of biennial mammography increased by 6.5 percentage points (95% CI, 3.7 to
9.4) for white women and 8.4 percentage points (95% CI, 2.5 to 14.4) for black
women but was almost unchanged for Hispanic women (0.4 percentage points; 95% CI,
-7.3 to 8.1). CONCLUSIONS: The elimination of cost sharing for screening
mammography under the ACA was associated with an increase in rates of use of this
service among older women for whom screening is recommended. The effect was
attenuated among women living in areas with lower educational attainment and was
negligible among Hispanic women. (Funded by the National Institute on Aging.).
PMID- 29342380
TI - E-Cigarettes and the Harm-Reduction Continuum.
PMID- 29342382
TI - Noninferiority Trials.
PMID- 29342381
TI - Long-Term Follow-up of Monoclonal Gammopathy of Undetermined Significance.
AB - BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) occurs in
approximately 3% of persons 50 years of age or older. METHODS: We studied 1384
patients who were residing in southeastern Minnesota and in whom MGUS was
diagnosed at the Mayo Clinic in the period from 1960 through 1994; the median
follow-up was 34.1 years (range, 0.0 to 43.6). The primary end point was
progression to multiple myeloma or another plasma-cell or lymphoid disorder.
RESULTS: During 14,130 person-years of follow-up, MGUS progressed in 147 patients
(11%), a rate that was 6.5 times (95% confidence interval [CI], 5.5 to 7.7) as
high as the rate in the control population. The risk of progression without
accounting for death due to competing causes was 10% at 10 years, 18% at 20
years, 28% at 30 years, 36% at 35 years, and 36% at 40 years. Among patients with
IgM MGUS, the presence of two adverse risk factors - namely, an abnormal serum
free light-chain ratio (ratio of kappa to lambda free light chains) and a high
serum monoclonal protein (M protein) level (>=1.5 g per deciliter) - was
associated with a risk of progression at 20 years of 55%, as compared with 41%
among patients who had one adverse risk factor and 19% among patients who had
neither risk factor. Among patients with non-IgM MGUS, the risk of progression at
20 years was 30% among those who had the two risk factors, 20% among those who
had one risk factor, and 7% among those who had neither risk factor. Patients
with MGUS had shorter survival than was expected in the control population of
Minnesota residents of matched age and sex (median, 8.1 vs. 12.4 years; P<0.001).
CONCLUSIONS: Significant differences were noted in the risk of progression
between patients with IgM MGUS and those with non-IgM MGUS. Overall survival was
shorter among patients with MGUS than was expected in a matched control
population. (Funded by the National Cancer Institute.).
PMID- 29342383
TI - Rib Fracture Associated with Bordetella pertussis Infection.
PMID- 29342384
TI - Evaluation and Management of Lower-Extremity Ulcers.
PMID- 29342385
TI - Ovarian Cancer Treatment - Are We Getting Warmer?
PMID- 29342386
TI - Butterfly Glioma.
PMID- 29342387
TI - Nudge Units to Improve the Delivery of Health Care.
PMID- 29342388
TI - Crisis in the Sustainability of the U.S. Blood System.
PMID- 29342389
TI - A Neglected Epidemic.
PMID- 29342391
TI - Case 2-2018. A 41-Year-Old Woman with Vision Disturbances and Headache.
PMID- 29342390
TI - Household-Contact Investigation for Detection of Tuberculosis in Vietnam.
AB - BACKGROUND: Active case finding is a top priority for the global control of
tuberculosis, but robust evidence for its effectiveness in high-prevalence
settings is lacking. We sought to evaluate the effectiveness of household-contact
investigation, as compared with standard, passive measures alone, in Vietnam.
METHODS: We performed a cluster-randomized, controlled trial at clinics in 70
districts (local government areas with an average population of approximately
500,000 in urban areas and 100,000 in rural areas) in eight provinces of Vietnam.
Health workers at each district clinic or hospital were assigned to perform
either household-contact intervention plus standard passive case finding
(intervention group) or passive case finding alone (control group). In the
intervention districts, household contacts of patients with positive results for
tuberculosis on sputum smear microscopy (smear-positive tuberculosis) were
invited for clinical assessment and chest radiography at baseline and at 6, 12,
and 24 months. The primary outcome was the cumulative incidence of registered
cases of tuberculosis among household contacts of patients with tuberculosis
during a 2-year period. RESULTS: In 70 selected districts, we enrolled 25,707
household contacts of 10,964 patients who had smear-positive pulmonary
tuberculosis. In the 36 districts that were included in the intervention group,
180 of 10,069 contacts were registered as having tuberculosis (1788 cases per
100,000 population), as compared with 110 of 15,638 contacts (703 per 100,000) in
the control group (relative risk of the primary outcome in the intervention
group, 2.5; 95% confidence interval [CI], 2.0 to 3.2; P<0.001); the relative risk
of smear-positive disease among household contacts in the intervention group was
6.4 (95% CI, 4.5 to 9.0; P<0.001). CONCLUSIONS: Household-contact investigation
plus standard passive case finding was more effective than standard passive case
finding alone for the detection of tuberculosis in a high-prevalence setting at 2
years. (Funded by the Australian National Health and Medical Research Council;
ACT2 Australian New Zealand Clinical Trials Registry number, ACTRN12610000600044
.).
PMID- 29342392
TI - Toxic Alcohols.
PMID- 29342394
TI - Identification of Linear and Nonlinear Sensory Processing Circuits from Spiking
Neuron Data.
AB - Inferring mathematical models of sensory processing systems directly from input
output observations, while making the fewest assumptions about the model
equations and the types of measurements available, is still a major issue in
computational neuroscience. This letter introduces two new approaches for
identifying sensory circuit models consisting of linear and nonlinear filters in
series with spiking neuron models, based only on the sampled analog input to the
filter and the recorded spike train output of the spiking neuron. For an ideal
integrate-and-fire neuron model, the first algorithm can identify the spiking
neuron parameters as well as the structure and parameters of an arbitrary
nonlinear filter connected to it. The second algorithm can identify the
parameters of the more general leaky integrate-and-fire spiking neuron model, as
well as the parameters of an arbitrary linear filter connected to it. Numerical
studies involving simulated and real experimental recordings are used to
demonstrate the applicability and evaluate the performance of the proposed
algorithms.
PMID- 29342395
TI - Indistinguishable Synapses Lead to Sparse Networks.
AB - Neurons integrate information from many neighbors when they process information.
Inputs to a given neuron are thus indistinguishable from one another. Under the
assumption that neurons maximize their information storage, indistinguishability
is shown to place a strong constraint on the distribution of strengths between
neurons. The distribution of individual synapse strengths is found to follow a
modified Boltzmann distribution with strength proportional to [Formula: see
text]. The model is shown to be consistent with experimental data from
Caenorhabditis elegans connectivity and in vivo synaptic strength measurements.
The [Formula: see text] dependence helps account for the observation of many zero
or weak connections between neurons or sparsity of the neural network.
PMID- 29342393
TI - Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer.
AB - BACKGROUND: Treatment of newly diagnosed advanced-stage ovarian cancer typically
involves cytoreductive surgery and systemic chemotherapy. We conducted a trial to
investigate whether the addition of hyperthermic intraperitoneal chemotherapy
(HIPEC) to interval cytoreductive surgery would improve outcomes among patients
who were receiving neoadjuvant chemotherapy for stage III epithelial ovarian
cancer. METHODS: In a multicenter, open-label, phase 3 trial, we randomly
assigned 245 patients who had at least stable disease after three cycles of
carboplatin (area under the curve of 5 to 6 mg per milliliter per minute) and
paclitaxel (175 mg per square meter of body-surface area) to undergo interval
cytoreductive surgery either with or without administration of HIPEC with
cisplatin (100 mg per square meter). Randomization was performed at the time of
surgery in cases in which surgery that would result in no visible disease
(complete cytoreduction) or surgery after which one or more residual tumors
measuring 10 mm or less in diameter remain (optimal cytoreduction) was deemed to
be feasible. Three additional cycles of carboplatin and paclitaxel were
administered postoperatively. The primary end point was recurrence-free survival.
Overall survival and the side-effect profile were key secondary end points.
RESULTS: In the intention-to-treat analysis, events of disease recurrence or
death occurred in 110 of the 123 patients (89%) who underwent cytoreductive
surgery without HIPEC (surgery group) and in 99 of the 122 patients (81%) who
underwent cytoreductive surgery with HIPEC (surgery-plus-HIPEC group) (hazard
ratio for disease recurrence or death, 0.66; 95% confidence interval [CI], 0.50
to 0.87; P=0.003). The median recurrence-free survival was 10.7 months in the
surgery group and 14.2 months in the surgery-plus-HIPEC group. At a median follow
up of 4.7 years, 76 patients (62%) in the surgery group and 61 patients (50%) in
the surgery-plus-HIPEC group had died (hazard ratio, 0.67; 95% CI, 0.48 to 0.94;
P=0.02). The median overall survival was 33.9 months in the surgery group and
45.7 months in the surgery-plus-HIPEC group. The percentage of patients who had
adverse events of grade 3 or 4 was similar in the two groups (25% in the surgery
group and 27% in the surgery-plus-HIPEC group, P=0.76). CONCLUSIONS: Among
patients with stage III epithelial ovarian cancer, the addition of HIPEC to
interval cytoreductive surgery resulted in longer recurrence-free survival and
overall survival than surgery alone and did not result in higher rates of side
effects. (Funded by the Dutch Cancer Society; ClinicalTrials.gov number,
NCT00426257 ; EudraCT number, 2006-003466-34 .).
PMID- 29342396
TI - Cross-Domain Metric and Multiple Kernel Learning Based on Information Theory.
AB - Learning an appropriate distance metric plays a substantial role in the success
of many learning machines. Conventional metric learning algorithms have limited
utility when the training and test samples are drawn from related but different
domains (i.e., source domain and target domain). In this letter, we propose two
novel metric learning algorithms for domain adaptation in an information
theoretic setting, allowing for discriminating power transfer and standard
learning machine propagation across two domains. In the first one, a cross-domain
Mahalanobis distance is learned by combining three goals: reducing the
distribution difference between different domains, preserving the geometry of
target domain data, and aligning the geometry of source domain data with label
information. Furthermore, we devote our efforts to solving complex domain
adaptation problems and go beyond linear cross-domain metric learning by
extending the first method to a multiple kernel learning framework. A convex
combination of multiple kernels and a linear transformation are adaptively
learned in a single optimization, which greatly benefits the exploration of prior
knowledge and the description of data characteristics. Comprehensive experiments
in three real-world applications (face recognition, text classification, and
object categorization) verify that the proposed methods outperform state-of-the
art metric learning and domain adaptation methods.
PMID- 29342397
TI - Imaging the Spatiotemporal Dynamics of Cognitive Processes at High Temporal
Resolution.
AB - This letter presents a noninvasive imaging technique that captures the exact
timing and locations of cortical activity sequences that are specific to a
cognitive process. These precise spatiotemporal sequences can be detected in the
human brain as specific time-position pattern associated with a cognitive task.
They are consistent with direct measurements of population activity recorded in
nonhuman primates, thus suggesting that specific time-position patterns
associated with a cognitive task can be identified. This imaging technique is
based on estimating the amplitude of cortical current dipoles from MEG
recordings. Although the spatial resolution of these estimations is poor
(approximately 2 cm), the temporal resolution is high (milliseconds). We show
that within these cortical current dipoles, time points of cortical activation
can be identified as brief amplitude undulations and that sequences of these
transients repeat with millisecond accuracy, hence making it possible to treat
the timing of these transients as point processes. We illustrate the feasibility
of finding spatiotemporal templates specific to the cognitive processes
associated with following the rhythm of drumbeats that involve the activation at
multiple cortical and cerebellar loci. These templates evolve at an accuracy of a
few milliseconds. This approach can thus pave the way for new perspectives on the
relationships between brain dynamics and cognition.
PMID- 29342398
TI - Adaptive Structure Concept Factorization for Multiview Clustering.
AB - Most existing multiview clustering methods require that graph matrices in
different views are computed beforehand and that each graph is obtained
independently. However, this requirement ignores the correlation between multiple
views. In this letter, we tackle the problem of multiview clustering by jointly
optimizing the graph matrix to make full use of the data correlation between
views. With the interview correlation, a concept factorization-based multiview
clustering method is developed for data integration, and the adaptive method
correlates the affinity weights of all views. This method differs from
nonnegative matrix factorization-based clustering methods in that it can be
applicable to data sets containing negative values. Experiments are conducted to
demonstrate the effectiveness of the proposed method in comparison with state-of
the-art approaches in terms of accuracy, normalized mutual information, and
purity.
PMID- 29342399
TI - Information-Theoretic Bounds and Approximations in Neural Population Coding.
AB - While Shannon's mutual information has widespread applications in many
disciplines, for practical applications it is often difficult to calculate its
value accurately for high-dimensional variables because of the curse of
dimensionality. This article focuses on effective approximation methods for
evaluating mutual information in the context of neural population coding. For
large but finite neural populations, we derive several information-theoretic
asymptotic bounds and approximation formulas that remain valid in high
dimensional spaces. We prove that optimizing the population density distribution
based on these approximation formulas is a convex optimization problem that
allows efficient numerical solutions. Numerical simulation results confirmed that
our asymptotic formulas were highly accurate for approximating mutual information
for large neural populations. In special cases, the approximation formulas are
exactly equal to the true mutual information. We also discuss techniques of
variable transformation and dimensionality reduction to facilitate computation of
the approximations.
PMID- 29342400
TI - A Unifying Framework of Synaptic and Intrinsic Plasticity in Neural Populations.
AB - A neuronal population is a computational unit that receives a multivariate, time
varying input signal and creates a related multivariate output. These neural
signals are modeled as stochastic processes that transmit information in real
time, subject to stochastic noise. In a stationary environment, where the input
signals can be characterized by constant statistical properties, the systematic
relationship between its input and output processes determines the computation
carried out by a population. When these statistical characteristics unexpectedly
change, the population needs to adapt to its new environment if it is to maintain
stable operation. Based on the general concept of homeostatic plasticity, we
propose a simple compositional model of adaptive networks that achieve invariance
with regard to undesired changes in the statistical properties of their input
signals and maintain outputs with well-defined joint statistics. To achieve such
invariance, the network model combines two functionally distinct types of
plasticity. An abstract stochastic process neuron model implements a generalized
form of intrinsic plasticity that adapts marginal statistics, relying only on
mechanisms locally confined within each neuron and operating continuously in
time, while a simple form of Hebbian synaptic plasticity operates on synaptic
connections, thus shaping the interrelation between neurons as captured by a
copula function. The combined effect of both mechanisms allows a neuron
population to discover invariant representations of its inputs that remain stable
under a wide range of transformations (e.g., shifting, scaling and (affine
linear) mixing). The probabilistic model of homeostatic adaptation on a
population level as presented here allows us to isolate and study the individual
and the interaction dynamics of both mechanisms of plasticity and could guide the
future search for computationally beneficial types of adaptation.
PMID- 29342402
TI - Cutaneous Cryptococcosis Mimicking Leishmaniasis.
PMID- 29342401
TI - Matched Placental and Circulating Plasmodium falciparum Parasites are Genetically
Homologous at the var2csa ID1-DBL2X Locus by Deep Sequencing.
AB - In pregnancy-associated malaria, infected erythrocytes accumulate in the
placenta. It is unclear if in polyclonal infections this results in distinct
peripheral and placental parasite populations. We used long amplicon deep
sequencing of Plasmodium falciparum var2csa ID1-DBL2X from 15 matched peripheral
and placental samples collected at delivery from a high transmission area to
determine genetic homology. Despite substantial sequence variation and detecting
23 haplotypes, the matched pairs mostly contained the same genetic variants, with
11 pairs sharing 100% of their variants, whereas others showed some
heterogeneity. Thus, at delivery, peripheral and placental parasites appear to
intermix and placental genotypes can be inferred through peripheral sampling.
PMID- 29342403
TI - 18F-FDG PET/CT in the Follow-Up of Mucosal Leishmaniasis.
PMID- 29342404
TI - Association between Severity of Liver Disease, Frequency of Helicobacter pylori
Infection, and Degree of Gastric Lesion in Egyptian Patients with Hepatitis B
Virus Infection.
AB - The relationship between hepatitis B virus (HBV) infection, severity of liver
disease, frequency of Helicobacter pylori infection, and degree of gastric
lesions was not yet fully investigated in Egyptian patients. The present work was
performed on 100 Egyptian patients with HBV from the National Hepatology and
Tropical Medicine Institute and 70 healthy volunteers as control group. The
participants were subjected to full medical history taking, clinical examination,
and laboratory investigations. All patients were positive for HBV surface antigen
(HBV sAg), HBV DNA, and negative for hepatitis C virus antibodies. The severity
of the liver disease was assessed using Child-Pugh scoring system. Screening of
all participants for H. pylori Ag in stool was performed. Biopsy specimens were
taken from the gastric lesions of H. pylori-infected patients for
histopathological examination. The mean age of the patients and control group
were 34.9 and 33.4 years, respectively. The levels of the liver enzymes were
statistically higher in HBV patients than the control group. Helicobacter pylori
Ag in stool was detected in 45.7% of the control group, and a higher percentage
(60%) was detected in the patients group. Chronic gastritis with glandular
atrophy and metaplasia was found in 15.6% of patients of Child-Pugh A, 70% of
Child-Pugh B, and 100% of Child-Pugh C. It could be concluded that the prognosis
of the liver disease significantly influences the severity of the gastric
pathology in H. pylori infection.
PMID- 29342405
TI - Human Laryngeal Infection by Clinostomum complanatum.
PMID- 29342406
TI - Looking Back at 2017 with ASTMH Past President Patricia Walker: Political
Challenges Remind Her that "Optimism is a Moral Imperative".
PMID- 29342407
TI - Vitamin D and iron deficiencies in children and adolescents with cerebral palsy.
AB - INTRODUCTION: Children and adolescents with cerebral palsy (CP) are at a greater
risk of malnutrition and micronutrient deficiencies. Two deficiencies that we can
study and treat are vitaminD (VD) and iron deficiencies; however, no studies have
described these deficiencies in Chile. OBJECTIVE: To describe the status of VD
and iron in patients with CP and evaluate the relationship with certain factors
associated with deficiencies of these micronutrients. PATIENTS AND METHOD: We
performed a descriptive, cross-sectional study including 69 patients aged between
2 and 21years, from two public hospitals. Data were obtained on demographic
variables, motor function, use of feeding tube, and pharmacological treatment. We
performed a nutritional assessment according to patterns of CP and determined 25
hydroxyvitaminD (25[OH]D) ferritin, and albumin levels. RESULTS: Patients' mean
age was 11.1+/-4.9years; 43 (62.3%) were male; and 56 (81.2%) had moderate-to
severe CP. Thirty-five (50.7%) used a nasogastric tube and/or gastrostomy; 15.4%
were underweight and 73.8% were eutrophic, all with normal height. Twenty (29%)
and 4 patients (6.2%) received VD and iron supplementation, respectively.
Albuminaemia was normal in all patients. Mean 25(OH)D level was 24.3+/-8.8ng/mL;
33 patients (47.8%) had insufficiency and 21 (30.4%) deficiency; 36 patients
(52.2%) had low ferritin levels. There was no association between 25(OH)D level
and the other variables studied. Low ferritin levels were found to be associated
with older age (P=.03), being male (P=.006), and feeding tube use (P=.006).
CONCLUSIONS: The patients studied mainly had moderate-to-severe CP, with a high
frequency of suboptimal VD values and low plasma ferritin; few patients received
VD and/or iron supplementation. We suggest monitoring 25(OH)D and ferritin levels
due to the high rate of deficiency of these nutrients; public hospitals should be
equipped with drugs to treat these deficiencies.
PMID- 29342408
TI - The role of regulatory RNAs (miRNAs) in asthma.
AB - INTRODUCTION: Recently, a great deal of attention has been paid to the
investigation of regulatory functions of microRNA. Currently, many different
mechanisms involved in the pathogenesis of asthma are known, but the whole
picture of pathogenesis has not yet been studied. CONCLUSIONS: MicroRNAs play an
important role in the regulation of many cellular processes. Undoubtedly, these
regulatory molecules are involved in the pathogenesis of asthma, and therefore
can be potential targets for treatment.
PMID- 29342409
TI - Development and characterization of an allergoid of cat dander for immunotherapy.
AB - BACKGROUND: Allergy to cats is a frequent cause of sensitization to indoor
allergens and currently there are few alternatives to specific immunotherapy with
cat native extracts. The objective is to develop and characterize a new allergoid
to increase the tools available for use in clinical practice. METHODS: The
allergoid cat dander extract (ACD) was developed from a native cat dander extract
(NCD) by modification with glutaraldehyde, and the optimal process control was
determined by SDS-PAGE, DOT BLOT and determination of free amine groups. The ACD
was characterized in protein profile by SDS-PAGE, size exclusion chromatography
(SEC) and peptide footprint. The allergenic profile of ACD was determined by
immunoblot, IgE CAP inhibition and IgG competition ELISA. The major allergen
content in NCD was obtained by the ELISA sandwich protocol and was extrapolated
to ACD. RESULTS: The control process determined the optimal development of the
allergoid. The ACD obtained contains 182.28MUg/mg of protein and 11.90MUg/mg of
Fel d 1. SDS-PAGE and SEC confirmed the presence of high molecular weight
proteins in ACD, and the peptide footprint showed the presence of Fel d 1 and Fel
d 7. The high degree of polymerization was evidenced with the determination of
the reduction of lysine residues in the allergoid, resulting 91.96%. The ACD
showed a significant loss of allergenicity respect to NCD, while the IgG-binding
capacity was maintained. CONCLUSIONS: The ACD obtained presents a good safety
profile, so would be a good alternative for treatment of cat allergy.
PMID- 29342410
TI - Palliative non-resective surgery for drug-resistant epilepsy.
PMID- 29342411
TI - Lumbar tattoos and epidural analgesia in 2018: time to let it go?
PMID- 29342412
TI - Reply to Christian Seitz's Letter to the Editor re: Zhangqun Ye, Guohua Zeng,
Huan Yang, et al. Efficacy and Safety of Tamsulosin in Medical Expulsive Therapy
for Distal Ureteral Stones with Renal Colic: A Multicenter, Randomized, Double
blind, Placebo-controlled Trial. Eur Urol 2018;73:385-91.
PMID- 29342413
TI - Rapid detection of blaKPC directly from surveillance rectal swabs by EasyQ KPC.
AB - The performance of EasyQ KPC assay was evaluated for the first time for blaKPC
detection directly from surveillance rectal swabs without broth enrichment. Using
conventional polymerase chain reaction as gold standard method, EasyQ KPC and
culture-based molecular tests demonstrated a sensitivity/specificity of
100%/87.3% and 83.3%/98.2%, respectively.
PMID- 29342414
TI - Bacilli community of saline-alkaline soils from the Ararat Plain (Armenia)
assessed by molecular and culture-based methods.
AB - The bacterial community composition in the A horizon of a natural saline-alkaline
soil located in Ararat Plain (Armenia) was studied using molecular and culture
based methods The sequence analysis of a 16S rRNA gene clone library and
denaturing gradient gel electrophoresis (DGGE) profiles indicated dominance of
Firmicutes populations. The majority of the sequences of the bacterial 16S rRNA
gene library were close relatives of representatives belonging to the genera
Halobacillus (41.2%), Piscibacillus (23.5%), Bacillus (23.5%) and Virgibacillus
(11.8%). Eight novel moderately halophilic bacilli isolates were successfully
obtained from the enriched cultures of the saline-alkaline soil samples. 16S rRNA
gene sequence analyses of isolates revealed their affiliation (97.7-99.7%
similarity) to representatives of the genera Bacillus, Piscibacillus and
Halobacillus. All isolates were able to tolerate high concentrations of NaCl and
highly alkaline conditions. This is the first study combining cultivation
independent and -dependent approaches to reveal the bacterial diversity of the
saline-alkaline soils of Ararat Plain and it suggested an important role of
bacilli as key microbes in biogeochemical cycles of these environments.
PMID- 29342415
TI - Lysosomes-targeting imaging and anticancer properties of novel bis-naphthalimide
derivatives.
AB - A series of novel N,N-bis(3-aminopropyl)methylamine bridged bis-naphthalimide
derivatives NI1-NI8 containing saturated nitrogenous heterocycles were designed
and synthesized, their cytotoxic activities against Hela, MCF-7, A549 and MGC-803
cells were investigated, Compounds NI1-NI4 modified with piperidine and
piperazine exhibited good and selective cytotoxic activity, for instance,
compounds NI1 and NI4 showed potent cytotoxic activity against Hela cells and MGC
803 cells with the IC50 values of 2.89, 060, 2.73 and 1.60 MUM, respectively,
better than the control drug (Amonafide). However, compounds NI5-NI8 conjugated
with pyrrole derivatives showed weak cytotoxic activities against the all tested
cell lines. Furthermore, their DNA binding properties, fluorescence imaging and
cell cycle were investigated. Interestingly, compounds NI1 and NI4 showed
fluorescence enhancement because of the strong binding with Ct-DNA, and exhibited
fluorescence imaging with Hela cells on the lysosomes.
PMID- 29342417
TI - Editor's Choice - A Study of the Cost-effectiveness of Fenestrated/branched EVAR
Compared with Open Surgery for Patients with Complex Aortic Aneurysms at 2 Years.
AB - OBJECTIVES: The aim was to assess the cost-effectiveness of fenestrated and
branched stent grafts (f/b EVAR) compared with open surgical repair (OSR) in
thoraco-abdominal or complex abdominal aortic aneurysms (TAAA/AAA) at 2 years.
METHODS: Two matched cohorts of patients with TAAA or complex AAA were compared
after a follow-up of two years. Patients included in the WINDOW French
multicentre prospective registry were treated by f/b EVAR, and OSR patients were
extracted from the French national hospital discharge database. All cause
mortality was assessed along with readmissions and hospital costs. The
association between treatment and 2 year mortality was assessed by
uni/multivariate Cox regression analyses using pre- and post-operative
characteristics. Incremental cost-effectiveness ratios (ICER) were estimated for
para/juxtarenal AAA, and infra- and supra-diaphragmatic TAAA. RESULTS: A total of
268 high risk patients were treated by f/b EVAR and 1678 average or low risk
patients were treated with OSR during the same period. Mortality did not
significantly differ between the groups (14.9% vs. 11.8%, p = .150) and
multivariate Cox regressions did not find an association between 2 year mortality
and treatment. Similar proportions of patients were readmitted at least once
(69.7% with f/b EVAR vs. 64.2% with OSR, p = .096) but f/b EVAR patients had more
readmissions on average (2.2 vs. 1.7, p = .001). Two year hospital costs were
higher in the f/b EVAR group (?46,039 vs. ?22,779, p < .001). At 2 years, f/b
EVAR was dominated (more expensive and less effective), except in the supra
diaphragmatic TAAA subgroup with an ICER of ?42,195,800 per death averted.
CONCLUSIONS: f/b EVAR in high risk patients offers similar 2 year mortality to
OSR performed in lower risk patients but at a higher cost. The cost is mainly
driven by the cost of the stent graft, which is not compensated for by lower
healthcare resource consumption. Further studies are necessary to evaluate the
cost-effectiveness in low risk f/b EVAR patients who may experience fewer
complications.
PMID- 29342418
TI - Functional characterization of 9 CYP2A13 allelic variants by assessment of
nicotine C-oxidation and coumarin 7-hydroxylation.
AB - Cytochrome P450 2A13 (CYP2A13) is responsible for the metabolism of chemical
compounds such as nicotine, coumarin, and tobacco-specific nitrosamine. Several
of these compounds have been recognized as procarcinogens activated by CYP2A13.
We recently showed that CYP2A13*2 contributes to inter-individual variations
observed in bladder cancer susceptibility because CYP2A13*2 might cause a
decrease in enzymatic activity. Other CYP2A13 allelic variants may also affect
cancer susceptibility. In this study, we performed an in vitro analysis of the
wild-type enzyme (CYP2A13.1) and 8 CYP2A13 allelic variants, using nicotine and
coumarin as representative CYP2A13 substrates. These CYP2A13 variant proteins
were heterologously expressed in 293FT cells, and the kinetic parameters of
nicotine C-oxidation and coumarin 7-hydroxylation were estimated. The quantities
of CYP2A13 holoenzymes in microsomal fractions extracted from 293FT cells were
determined by measuring reduced carbon monoxide-difference spectra. The kinetic
parameters for CYP2A13.3, CYP2A13.4, and CYP2A13.10 could not be determined
because of low metabolite concentrations. Five other CYP2A13 variants (CYP2A13.2,
CYP2A13.5, CYP2A13.6, CYP2A13.8, and CYP2A13.9) showed markedly reduced enzymatic
activity toward both substrates. These findings provide insights into the
mechanism underlying inter-individual differences observed in genotoxicity and
cancer susceptibility.
PMID- 29342416
TI - Identification of novel quinazolinedione derivatives as RORgammat inverse
agonist.
AB - Novel small molecules were synthesized and evaluated as retinoic acid receptor
related orphan receptor-gamma t (RORgammat) inverse agonists for the treatment of
inflammatory and autoimmune diseases. A hit compound, 1, was discovered by high
throughput screening of our compound library. The structure-activity relationship
(SAR) study of compound 1 showed that the introduction of a chlorine group at the
3-position of 4-cyanophenyl moiety increased the potency and a 3-methylpentane
1,5-diamide linker is favorable for the activity. The carbazole moiety of 1 was
also optimized; a quinazolinedione derivative 18i suppressed the increase of IL
17A mRNA level in the lymph node of a rat model of experimental autoimmune
encephalomyelitis (EAE) upon oral administration. These results indicate that the
novel quinazolinedione derivatives have great potential as orally available small
molecule RORgammat inverse agonists for the treatment of Th17-driven autoimmune
diseases. A U-shaped bioactive conformation of this chemotype with RORgammat
protein was also observed.
PMID- 29342419
TI - Investigation of the transport of xanthine dehydrogenase inhibitors by the urate
transporter ABCG2.
AB - Hyperuricemia induces gout and kidney stones and accelerates the progression of
renal and cardiovascular diseases. Adenosine 5'-triphosphate-binding cassette
subfamily G member 2 (ABCG2) is a urate transporter, and common dysfunctional
variants of ABCG2, non-functional Q126X (rs72552713) and semi-functional Q141K
(rs2231142), are risk factors for hyperuricemia and gout. A recent genome wide
association study suggested that allopurinol, a serum uric acid-lowering drug
that inhibits xanthine dehydrogenase, is a potent substrate of ABCG2. In this
study, we aimed to examine the transport of xanthine dehydrogenase inhibitors via
ABCG2. Our results show that ABCG2 transports oxypurinol, an active metabolite of
allopurinol, whereas allopurinol and febuxostat, a new xanthine dehydrogenase
inhibitor, are not substrates of ABCG2. The amount of oxypurinol transported by
ABCG2 vesicles significantly increased in the presence of ATP, compared to that
observed with mock vesicles. Since the half-life of oxypurinol is longer than
that of allopurinol, the xanthine dehydrogenase-inhibiting effect of allopurinol
mainly depends on its metabolite, oxypurinol. Our results indicate that the serum
level of oxypurinol would increase in patients with ABCG2 dysfunction.
PMID- 29342420
TI - [Use of bronchial blocker in emergent thoracotomy in presence of upper airway
hemorrhage, and cervical spine fracture: a difficult decision].
AB - Female, 85 y.o., weighting 60kg, multiple trauma patient. After an initial
laparotomy, an emergent thoracotomy was performed using a bronchial blocker for
lung isolation (initial active suction was applied). During surgery, bronchial
cuff was deflated, causing a self-limited tracheal blood flooding. A second lung
isolation was attempted but it was not as effective as initially. Probably, a
lung collapse with the same bronchial blocker was impaired in the second attempt
because of the obstruction of bronchial blocker lumen by intraoperative
endobronchial hemorrhage. Bronchial blocker active suction may contribute to
obtain or accelerate lung collapse, particularly in patients that do not tolerate
ventilator disconnection technique or lung surgical compression. The use of
bronchial blockers technology was a valuable alternative to double lumen tubes in
this case of emergent thoracotomy in the context of a patient having thoracic,
abdominal trauma, severe laceration of tongue and apophysis odontoid fracture
associated to massive hemorrhage, despite several pitfalls that could compromise
its use. The authors intend to discuss the advantages and disadvantages of
bronchial blockers comparing to double-lumen tubes for lung isolation, and the
risks of our approach, in this complex multitrauma case.
PMID- 29342421
TI - The relation between plasma alpha-synuclein level and clinical symptoms or signs
of Parkinson's disease.
AB - INTRODUCTION: Parkinson disease (PD) is the common neurodegenerative disease.
alpha-Synuclein (ASN), main aggregating protein in neural cells of CNS in PD, was
found in peripheral fluids. Testing ASN in plasma is potential test for diagnose
PD, but previous studies are controversial. The aim of this study was to
investigate if plasma ASN level may be a valuable biomarker, is the level of
plasma ASN concentration different in various motor subtypes of diseases, is
there a relation between the level of plasma ASN and the severity of motor
symptoms. METHODS: Patients with PD hospitalized in Neurology Department, Medical
College were performed sequencing the 8th and 9th exon of GBA gene. Next plasma
ASN level was tested in 58 patients with sequenced GBA gene and in 38 healthy
volunteers (HV), matched by the age (respectively 68.43 vs. 64.57 years of age)
and sex (female %, respectively: 43.10 vs.44.74). Patients were assessed with the
scales: UPDRS (II, III, IV), Hoehn-Yahr (HY) and qualified to PIGD or TD subtype.
For homogeneity of the group patients with GBA mutation were excluded from the
analysis. RESULTS: The ASN level did not differ between patients and HV
(respectively: 4.53 vs. 3.73ng/ml) and between patients with different subtypes.
There was inverse correlation between ASN and HY in PIGD subtype. CONCLUSIONS:
Plasma ASN level is not valuable marker of the disease. It does not differ in
subtypes of the disease. There is relation between plasma ASN level and the
severity of the disease in PIGD subtype.
PMID- 29342422
TI - Magnetic mesoporous molecularly imprinted polymers based on surface precipitation
polymerization for selective enrichment of triclosan and triclocarban.
AB - Novel magnetic mesoporous molecularly imprinted polymers (MMIPs) were prepared
based on surface precipitation polymerization using Triclosan (TCS) as template
and methacrylic acid as functional monomer. The synthesized MMIPs-TCS were
applied to the adsorbent of magnetic solid-phase extraction (MSPE) coupled with
HPLC for the enrichment and determination of TCS. The MMIPs-TCS were
characterized by fourier-transform infrared spectrometry (FTIR), scanning
electron microscopy (SEM), transmission electron microscopy (TEM), N2 adsorption
desorption transmission, and vibrating sample magnetometry. Under the optimum
condition, the MMIPs-TCS-MSPE-HPLC method shows low limits of detection (LODs)
(0.20-0.90 MUg L-1) and limits of quantification detection (LOQs) (0.66-2.97 MUg
L-1), wide linear ranges from 10.0 to 1000 MUg L-1 for each compound with
exception of 2,4,6-TCP from 20.0 to 1000 MUg L-1, and acceptable reproducibility
(relative standard deviation, RSD <6.6% for intra-day, RSD <8.1% for inter-day).
The satisfactory recoveries were in the range of 89.5%-108.4% with good RSDs less
than 8.0% at the three spiked levels of 20, 50 and 80 MUg L-1. Moreover, the
adsorption experiments show the MMIPs-TCS possess rapid binding affinity,
excellent magnetic response, specific selectivity and high adsorption capacity
toward TCS with a maximum adsorption capacity of 1955.8 MUg g-1.
PMID- 29342423
TI - Does Bed Rest or Fluid Supplementation Prevent Post-Dural Puncture Headache?
PMID- 29342424
TI - Corrigendum to "Effect of biochar on the presence of nutrients and ryegrass
growth in the soil from an abandoned indigenous coking site: The potential role
of biochar in the revegetation of contaminated site" [Sci. Total Environ. 601-602
(2017) 469-477].
PMID- 29342425
TI - Having the patience to allow a resident to operate on your grandmother.
PMID- 29342426
TI - Coronary transfer during arterial switch-the heart of the matter?
PMID- 29342427
TI - Reconstructive aortic valve surgery in the elderly: Techniques and outcomes.
AB - OBJECTIVES: The aim of the study was to evaluate operative techniques and long
term results after aortic valve or root repair in patients aged 75 years or more.
METHODS: Between November 2002 and January 2016, a total of 815 patients
underwent aortic valve or root repair. Among them were 100 patients aged 75 years
or more (mean, 78 +/- 3; range, 75-88 years), including 17 patients operated on
an emergency basis because of acute aortic dissection. None/trivial, mild,
moderate, and severe insufficiency grades were presented in 9, 23, 27, and 41
patients, respectively. The surgery comprised root repair, cusp repair, and a
combination of both in 45, 16, and 39 patients, respectively. RESULTS: Early (30
day) mortality and the rate of permanent neurologic deficit were 2% for each. The
follow-up was 99% complete, resulting in 427 patient/years. During the follow-up
period (mean duration, 4.3 +/- 3.2; range, 0.02-11.1 years), only 1 patient
developed a relevant aortic insufficiency and required aortic valve reoperation.
There were 24 late deaths, which occurred on average 50.0 +/- 40.6 months (range,
2.4-135.0) after surgery at the average patient age of 82 +/- 5 years (range, 75
90). Estimated survival at 5 and 8 years was 76.4% +/- 5.1% and 71.3% +/- 5.9%,
respectively, and was similar to those of the sex- and age-matched general
population. CONCLUSIONS: Reconstructive aortic valve surgery is a suitable and
justifiable surgical option in selected elderly patients undergoing operation by
surgeons with considerable experience in this kind of surgery. It offers low
cardiac and valve-related mortality and morbidity, leading to life expectancy
applicable to the patients' ages.
PMID- 29342428
TI - Importance of mapping the external environment in image-guided video-assisted
thoracoscopic surgery.
PMID- 29342429
TI - Size does really matter.
PMID- 29342430
TI - Tissue expander-stimulated lengthening of arteries for the treatment of midaortic
syndrome in children.
AB - BACKGROUND: Midaortic syndrome (MAS) is a rare condition characterized by
stenosis of the abdominal aorta. Patients with disease refractory to medical
management will usually require either endovascular therapy or surgery with use
of prosthetic graft material for bypass or patch angioplasty. We report our early
experience with a novel approach using a tissue expander (TE) to lengthen the
normal native arteries in children with MAS, allowing primary aortic repair
without the need for prosthetic graft material. METHODS: We conducted a
retrospective review of patients with MAS undergoing the TE-stimulated
lengthening of arteries (TESLA) procedure at our institution from 2010 to 2014.
Data are presented as mean (range). RESULTS: Five patients aged 4.8 years (3-8
years) underwent the TESLA procedure. Stages of this procedure include the
following: stage I, insertion of retroaortic TE; stage II, serial TE injections;
and stage III, final repair with excision of aortic stenosis and primary end-to
end aortic anastomosis. Stage II was completed in 4 months (1-9 months) with 12
(7-20) TE injections. Goal lengthening was achieved in all patients. Stage III
could not be completed in one patient because of extreme aortic inflammation,
which precluded safe excision of the aortic stenosis and required use of a
prosthetic bypass graft. The other four patients completed stage III with two
(one to three) additional vessels also requiring reconstruction (renal or
mesenteric arteries). At 3.2 years (1-6 years) of follow-up, all patients are
doing well. CONCLUSIONS: The TESLA procedure allows surgical correction of MAS
without the need for prosthetic grafts in young children who are still growing.
PMID- 29342431
TI - Comparison of access type on perioperative outcomes after endovascular aortic
aneurysm repair.
AB - OBJECTIVE: Endovascular aneurysm repair (EVAR) can be performed through
percutaneous or surgical access. Our goal was to assess the difference in
perioperative outcomes based on access type in a real-world setting. METHODS: The
Vascular Quality Initiative (VQI) database was queried for EVAR. Univariable
analysis and multivariable analysis were used to determine the independent effect
of access type. RESULTS: There were 8340 (64%) and 4747 (36%) EVAR procedures
performed through percutaneous and surgical access (3395 [72%] transverse and
1352 [28%] vertical incisions). In 347 cases (4%), percutaneous access failed.
Percutaneous access was performed more in patients who were younger and male, had
higher body mass index, were nonsmokers, and had commercial insurance.
Multivariable analysis showed that surgical transverse compared with percutaneous
access was associated with more cardiac complications (odds ratio, 1.53; 95%
confidence interval [CI], 1.14-2.05; P = .005), prolonged operative time (means
ratio [MR], 1.25; 95% CI, 1.23-1.27; P < .001), larger estimated blood loss (EBL;
MR, 1.51; 95% CI, 1.45-1.57; P < .001), and length of stay (LOS; MR, 1.28; 95%
CI, 1.23-1.32; P < .001). Open surgical access through vertical incisions
compared with percutaneous access was associated with prolonged operative time
(MR, 1.34; 95% CI, 1.31-1.37; P < .001), larger EBL (MR, 1.67; 95% CI, 1.58-1.77;
P < .001), and LOS (MR, 1.49; 95% CI, 1.42-1.57; P < .001). Open access through a
vertical incision compared with a transverse incision was associated with
prolonged operative time (MR, 1.07; 95% CI, 1.04-1.1; P < .001), larger EBL (MR,
1.1; 95% CI, 1.04-1.18; P = .001), and LOS (MR, 1.17; 95% CI, 1.1-1.23; P <
.001). Failed percutaneous access was seen more with previous bypass, ruptured
aneurysm repair, general anesthesia, female sex, obesity, coronary artery
disease, and preoperative aspirin use. Failed percutaneous access was associated
with increased cardiac complications (odds ratio, 2.48; 95% CI, 1.38-4.6; P =
.003), prolonged operative time (MR, 1.64; 95% CI, 1.56-1.72; P < .001), larger
EBL (MR, 3.27; 95% CI, 2.95-3.62; P < .001), and longer postoperative LOS (MR,
1.47; 95% CI, 1.35-1.6; P < .001). There was no independent effect of access type
on respiratory and lower extremity ischemic complications or mortality.
CONCLUSIONS: The rate of percutaneous access in this contemporary series is
higher than historically reported. Percutaneous access is associated with
decreased operative time, EBL, and LOS and should be considered when possible.
For open surgical access, transverse incisions are associated with lower
operative time, EBL, and LOS. Failed percutaneous access is associated with
higher cardiac complications as well as with operative time, EBL, and LOS. Extra
caution should be used with patients at high risk for failed percutaneous access.
Further prospective investigation is needed incorporating details about the
quality of the access vessel to determine the interactions of these risk factors.
PMID- 29342432
TI - Pharmacists' scope of practice in travel health: cregulations.
AB - OBJECTIVES: The primary objective of this study was to assess pharmacists'
authority to provide travel health services in each state and Washington, DC.
Secondary objectives were to determine the need for collaborative practice
agreements (CPAs), protocols, or prescriptions for this type of pharmacy practice
and to identify jurisdictions where pharmacists are able to practice as travel
health providers independent of CPAs or individual physician protocols. METHODS:
An online survey was developed to assess pharmacists' authority to administer
travel immunizations, furnish travel-related medications, and order travel
related laboratory tests. Open-ended items on scope of practice, training
requirements, and pending legislation or regulations were also included. The
survey was distributed to state pharmacy association executives. A member of the
research team searched pharmacy laws to clarify missing or inconsistent
responses. Data were analyzed using descriptive statistics. RESULTS: The survey
response rate was 76.5% (n = 39). Missing (n = 12) or conflicting (n = 6)
response issues were resolved. Thus, data were available for 100% of
jurisdictions. In most jurisdictions, pharmacists were able to provide one or
more components of this service. In 44 jurisdictions (86.3%), pharmacists were
allowed to administer travel immunizations. Twenty-seven jurisdictions (52.9%)
allowed pharmacists to furnish travel medications. Pharmacists in 23
jurisdictions (43.1%) could order travel health-related laboratory tests.
Pharmacists can practice independently in 1 state, but CPAs or individual
physician protocols are required elsewhere. CONCLUSIONS: To the authors'
knowledge, this study represents the first national pharmacists' travel health
scope-of-practice analysis. While pharmacists in many jurisdictions can provide
some components of travel health services, only one, New Mexico, currently allows
pharmacists to practice all aspects independently. Thus, pharmacists continue to
have an opportunity to expand scope of practice in travel health. Additional
research may help to drive increased access to and use of travel health care.
PMID- 29342433
TI - Applying the oath of a pharmacist to refugee health care.
PMID- 29342434
TI - Community pharmacists as first responders in Puerto Rico after Hurricane Maria.
PMID- 29342435
TI - The 2016 American Academy of Ophthalmology IRIS(r) Registry (Intelligent Research
in Sight) Database: Characteristics and Methods.
AB - PURPOSE: To describe the characteristics of the patient population included in
the 2016 IRIS(r) Registry (Intelligent Research in Sight) database for analytic
aims. DESIGN: Description of a clinical data registry. PARTICIPANTS: The 2016
IRIS Registry database consists of 17 363 018 unique patients from 7200 United
States-based ophthalmologists in the United States. METHODS: Electronic health
record (EHR) data were extracted from the participating practices and placed into
a clinical database. The approach can be used across dozens of EHR systems. MAIN
OUTCOME MEASURES: Demographic characteristics. RESULTS: The 2016 IRIS Registry
database includes data about patient demographics, top-coded disease conditions,
and visit rates. CONCLUSIONS: The IRIS Registry is a unique, large, real-world
data set that is available for analytics to provide perspectives and to learn
about current ophthalmic care and treatment outcomes. The IRIS Registry can be
used to answer questions about practice patterns, use, disease prevalence,
clinical outcomes, and the comparative effectiveness of different treatments.
Limitations of the data are the same limitations associated with EHR data in
terms of documentation errors or missing data and the lack of images. Currently,
open access to the database is not available, but there are opportunities for
researchers to submit proposals for analyses, for example through a Research to
Prevent Blindness and American Academy of Ophthalmology Award for IRIS Registry
Research.
PMID- 29342436
TI - Iris Melanoma Outcomes Based on the American Joint Committee on Cancer
Classification (Eighth Edition) in 432 Patients.
AB - PURPOSE: The American Joint Committee on Cancer (AJCC) classification was updated
to the eighth edition in January 2017, providing staging for iris melanoma. This
study evaluated outcomes of iris melanoma per the AJCC classification, eighth
edition. DESIGN: Retrospective case series. PARTICIPANTS: Four hundred thirty-two
patients with iris melanoma. METHODS: Management including tumor resection,
plaque radiotherapy, or enucleation. MAIN OUTCOME MEASURES: Local tumor
recurrence, melanoma-related systemic metastasis, and melanoma-related death.
RESULTS: Of 432 patients with iris melanoma, AJCC classification was category T1
(n = 324 [75%]), T2 (n = 83 [19%]), T3 (n = 2 [<1%]), and T4 (n = 23 [5%]). There
was no difference in age, race, gender, eye, or iris color among T categories.
Overall, Kaplan-Meier analysis of outcomes (at 5 and 10 years) revealed visual
acuity reduction by 3 lines or more (42% and 54%, respectively), secondary
glaucoma (29% and 33%, respectively), local recurrence (8% and 17%,
respectively), secondary enucleation (12% and 19%, respectively), lymph node
metastasis (1% and 1%, respectively), melanoma-related systemic metastasis (5%
and 10%, respectively), and melanoma-related death (3% and 4%, respectively).
Compared with T1 category, the hazard ratio (HR) for local recurrence in
nonenucleated eyes was 1.31 for T2, not evaluable (NE) for T3 (because of small
cohort), and 6.61 for T4; the HR for metastasis was 3.41 for T2, NE for T3
(because of small cohort), and 25.6 for T4; the HR for death was 7.51 for T2, NE
for T3 (because of small cohort), and 26.5 for T4; and the odds ratio for
enucleation was 1.23 for T2, 3.63 for T3, and 4.72 for T4. Features predictive of
melanoma-related metastasis (multivariate analysis) included secondary glaucoma
(P < 0.001; HR, 4.51), T2 category (vs. T1; P = 0.01; HR, 4.09), and T4 category
(vs. T1; P < 0.001; HR, 30.8). Features predictive of melanoma-related death
(multivariate analysis) included older age (P = 0.008; HR, 2.16 per 10-year
increase), T2 category (vs. T1; P = 0.005; HR, 8.07), and T4 category (vs. T1; P
< 0.001; HR, 20.3). CONCLUSIONS: The AJCC eighth edition classification provides
prognostic stratification of iris melanoma. By multivariate analysis, the ratio
for melanoma-related metastasis was 4 times greater in category T2 and 31 times
greater in T4 compared with T1. The ratio for melanoma-related death was 8 times
greater in category T2 and 20 times greater in T4 compared with T1. The cohort
size for T3 was too small to provide useful information.
PMID- 29342437
TI - Performance Rates Measured in the American Academy of Ophthalmology IRIS(c)
Registry (Intelligent Research in Sight).
PMID- 29342438
TI - Vitreoretinal Complications and Outcomes in 92 Eyes Undergoing Surgery for
Modified Osteo-Odonto-Keratoprosthesis: A 10-Year Review.
AB - PURPOSE: To analyze vitreoretinal (VR) complications and treatment outcomes in
eyes undergoing modified osteo-odonto-keratoprosthesis (OOKP) surgery. DESIGN:
Retrospective case series. PARTICIPANTS: All patients who underwent modified OOKP
(mOOKP) surgery at a tertiary eye-care center from March 2003 to February 2013
were included. METHODS: Medical records were reviewed for relevant medical
history, best-corrected visual acuity (BCVA), slit-lamp examination, ultrasound
scan, oral examination findings, and VR complications. MAIN OUTCOME MEASURES: The
BCVA at the last visit. Optimal anatomic outcome was attached retina with a
normal intraocular pressure at the last visit. RESULTS: A total of 92 eyes of 90
patients were included. Indications for OOKP included Stevens-Johnson syndrome (n
= 53), chemical injury (n = 36), and ocular cicatricial pemphigoid (n = 3). A
total of 41 eyes of 39 patients developed VR complications, including vitritis (n
= 21), retinal detachment (RD) (n = 12; primary RD = 5), retroprosthetic membrane
(RPM) (n = 10; primary RPM = 2), endophthalmitis (n = 8), vitreous hemorrhage
(VH) (n = 5; primary VH = 1), serous choroidal detachment (n = 5), hemorrhagic
choroidal detachment (n = 2), and leak-related hypotony (n = 1). Mean interval
from mOOKP surgery to occurrence of VR complication(s) was 43.8 months (median,
41.9 months; range, 0.2-95.5 months). After treatment of VR complication, visual
improvement was seen in 17 eyes (42%) (mean improvement = 1.2 logarithm of the
minimum angle of resolution [logMAR]; median, 0.8 logMAR; range, 0.1-2.5 logMAR),
visual decline in 7 eyes (14%) (mean decline in BCVA = 0.6 logMAR; median, 0.4
logMAR; range, 0.3-1.8 logMAR), and no change in BCVA in 17 eyes (42%). However,
BCVA >=6/60 was retained in 19 eyes and >=6/18 was retained in 9 eyes after final
VR treatment. CONCLUSIONS: Vitreoretinal complications constitute a significant
cause of visual morbidity in eyes undergoing mOOKP surgery and pose a challenging
situation to manage. However, appropriate and timely intervention can achieve
encouraging results.
PMID- 29342439
TI - Review of Ophthalmology Medical Professional Liability Claims in the United
States from 2006 through 2015.
AB - PURPOSE: To describe characteristics of closed medical professional liability
(MPL) claims against ophthalmologists in the United States. DESIGN: Retrospective
analysis of MPL claims from 2006-2015. Data were obtained from the Physician
Insurers Association of America (PIAA) Data Sharing Project (DSP). Comparison was
made between ophthalmology and all healthcare specialties for physician
demographics, prevalence and costs associated with closed claims, and resolution
of claims. The most prevalent chief medical factor, presenting medical condition,
operative procedure, outcomes, and resolution of ophthalmology claims were
compared between the 2006-2010 and 2011-2015 periods. PARTICIPANTS: From 2006
2015, 90 743 MPL claims were closed: 2.6% (2325/90 743) of closed claims and 2.2%
(564/24 670) of all paid claims were against ophthalmologists. METHODS:
Retrospective analysis of MPL claims captured by the PIAA DSP over a 10-year
period. MAIN OUTCOME MEASURES: Subspecialty pertaining to the claim, number of
claims closed and paid, indemnity paid, allocated loss adjustment expenses, chief
medical factor, presenting medical condition, operative procedure, outcome, and
resolution. RESULTS: Only 24% of closed claims against ophthalmologists resulted
in payment. Two-thirds were dropped, withdrawn, or dismissed. Ninety percent of
claims that received a verdict were favorable toward the ophthalmologist.
Cataract and cornea surgeries were the most prevalent and most costly operative
procedures, accounting for 50% of all claims and $47 641 376 and $32 570 148 in
total paid indemnity, respectively. Average indemnity was higher for corneal
procedures ($304 476) than vitreoretinal procedures ($270 141) or oculoplastic
procedures on the eyelid ($222 471) or orbit and eyeball ($183 467). The
prevalence and cost of claims related to endophthalmitis declined from 2006-2010
(n = 38/1160 [3.3%]; average indemnity, $516 875) period to the 2011-2015 (n =
26/1165 [2.2%]; average indemnity, $247 083) period. Average indemnity paid ($280
227 vs. $335 578) and amount spent on legal defense ($41 450 vs. $46 391) was
slightly lower among ophthalmologists compared with all healthcare specialties,
respectively. CONCLUSIONS: Ophthalmology has a relatively low number of
malpractice claims reported compared with other healthcare specialties and shows
less spending on average indemnity and defense. Further studies are needed to
investigate the reasons for the higher prevalence of claims related to cataract
and corneal surgeries and the higher average indemnity paid for corneal
procedures relative to vitreoretinal or oculoplastic procedures.
PMID- 29342440
TI - The critical warning sign of real-time brainstem auditory evoked potentials
during microvascular decompression for hemifacial spasm.
AB - OBJECTIVE: The aim of this study was to define the critical warning sign of real
time brainstem auditory evoked potential (BAEP) for predicting hearing loss (HL)
after microvascular decompression (MVD) for hemifacial spasm (HFS). METHODS: Nine
hundred and thirty-two patients with HFS who underwent MVD with intraoperative
monitoring (IOM) of BAEP were analyzed. We used a 43.9 Hz/s stimulation rate and
400 averaging trials to obtain BAEP. To evaluate HL, pure-tone audiometry and
speech discrimination scoring were performed before and one week after surgery.
We analyzed the incidence for postoperative HL according to BAEP changes and
calculated the diagnostic accuracy of significant warning criteria. RESULTS: Only
11 (1.2%) patients experienced postoperative HL. The group showing permanent loss
of wave V showed the largest percentage of postoperative HL (p < 0.001). No
patient who experienced only latency prolongation (>=1 ms) had postoperative HL.
Loss of wave V and latency prolongation (>=1 ms) with amplitude decrement (>=50%)
were highly associated with postoperative HL. CONCLUSIONS: Loss of wave V and
latency prolongation of 1 ms with amplitude decrement >=50% were the critical
warning signs of BAEP for predicting postoperative HL. SIGNIFICANCE: These
findings elucidate the critical warning sign of real-time BAEP.
PMID- 29342441
TI - Improving Professionalism Between Radiology and Emergency Medicine.
PMID- 29342442
TI - HIV-related Refractory Hodgkin Lymphoma: A Case Report of Complete Response to
Nivolumab.
PMID- 29342443
TI - Test-retest reliability of transcranial magnetic stimulation EEG evoked
potentials.
AB - BACKGROUND: Transcranial magnetic stimulation (TMS)-evoked potentials (TEPs),
recorded using electroencephalography (TMS-EEG), offer a powerful tool for
measuring causal interactions in the human brain. However, the test-retest
reliability of TEPs, critical to their use in clinical biomarker and
interventional studies, remains poorly understood. OBJECTIVE/HYPOTHESIS: We
quantified TEP reliability to: (i) determine the minimal TEP amplitude change
which significantly exceeds that associated with simply re-testing, (ii) locate
the most reliable scalp regions of interest (ROIs) and TEP peaks, and (iii)
determine the minimal number of TEP pulses for achieving reliability. METHODS:
TEPs resulting from stimulation of the left dorsolateral prefrontal cortex were
collected on two separate days in sixteen healthy participants. TEP peak
amplitudes were compared between alternating trials, split-halves of the same
run, two runs five minutes apart and two runs on separate days. Reliability was
quantified using concordance correlation coefficient (CCC) and smallest
detectable change (SDC). RESULTS: Substantial concordance was achieved in
prefrontal electrodes at 40 and 60 ms, centroparietal and left parietal ROIs at
100 ms, and central electrodes at 200 ms. Minimum SDC was found in the same
regions and peaks, particularly for the peaks at 100 and 200 ms. CCC, but not
SDC, reached optimal values by 60-100 pulses per run with saturation beyond this
number, while SDC continued to improve with increased pulse numbers. CONCLUSION:
TEPs were robust and reliable, requiring a relatively small number of trials to
achieve stability, and are thus well suited as outcomes in clinical biomarker or
interventional studies.
PMID- 29342445
TI - Case report of an uncommon case of drain-site hernia after colorectal surgery.
AB - BACKGROUND: trocar site herniation is a rare but potentially serious complication
of laparoscopic surgery. Data about drain site hernia after laparoscopic surgery
is scarce and anecdotal. CASE PRESENTATION: we report an uncommon case of drain
site hernia in a man undergone laparoscopic left colectomy for a colonic
adenocarcinoma who developed small bowel herniation in a 10 mm port site, in
which a 24 FR drain was inserted leaving a real free space of 2 mm. DISCUSSION:
laparoscopic approach has gained widespread acceptance in each surgical fields
because of the perceived better postoperative outcomes in terms of less pain,
faster recovery, and lower risk of incisional hernia. However, the risk of trocar
site hernia has been known since 1967. Different risk factors for the development
of trocar site hernia are described in literature: the trocar diameter and
design, preexisting fascial defects, enlargement of a port site to remove a
specimen, high blood glucose levels, obesity, increase intra-abdominal pressure
as in chronic obstructive airway disease or extensive manipulation of the trocar
during surgical intervention, which may enlarge the trocar site and thus induce
small bowel herniation. However, the most important recognized risk factor for
trocar site hernia is the size of the trocar. CONCLUSIONS: waiting for further
studies, the lesson to be learnt from this case report is that, even if the free
space after drain positioning is minimal, drain should not be positioned through
the 10 mm trocar to allow the closure of fascial defect in order to avoid any
herniation.
PMID- 29342444
TI - Scarlet Fever Epidemic in China Caused by Streptococcus pyogenes Serotype M12:
Epidemiologic and Molecular Analysis.
AB - From 2011, Hong Kong and mainland China have witnessed a sharp increase in
reported cases, with subsequent reports of epidemic scarlet fever in North Asia
and the United Kingdom. Here we examine epidemiological data and investigate the
genomic context of the predominantly serotype M12 Streptococcus pyogenes scarlet
fever isolates from mainland China. Incident case data was obtained from the
Chinese Nationwide Notifiable Infectious Diseases Reporting Information System.
The relative risk of scarlet fever in recent outbreak years 2011-2016 was
calculated using the median age-standardised incidence rate, compared to years
2003-2010 prior this outbreak. Whole genome sequencing was performed on 32 emm12
scarlet fever isolates and 13 emm12 non-scarlet fever isolates collected from
different geographic regions of China, and compared with 203 published emm12 S.
pyogenes genomes predominantly from scarlet fever outbreaks in Hong Kong (n=134)
and the United Kingdom (n=63). We found during the outbreak period (2011-2016),
the median age-standardised incidence in China was 4.14/100,000 (95% confidence
interval (CI) 4.11-4.18), 2.62-fold higher (95% CI 2.57-2.66) than that of
1.58/100,000 (95% CI 1.56-1.61) during the baseline period prior to the outbreak
(2003-2010). Highest incidence was reported for children 5years of age
(80.5/100,000). Streptococcal toxin encoding prophage phiHKU.vir and phiHKU.ssa
in addition to the macrolide and tetracycline resistant ICE-emm12 and ICE-HKU397
elements were found amongst mainland China multi-clonal emm12 isolates suggesting
a role in selection and expansion of scarlet fever lineages in China. Global
dissemination of toxin encoded prophage has played a role in the expansion of
scarlet fever emm12 clones. These findings emphasize the role of comprehensive
surveillance approaches for monitoring of epidemic human disease.
PMID- 29342446
TI - The impact of happy and angry faces on working memory in depressed adolescents.
AB - Recent cognitive models suggest that the ability to control emotional information
in working memory (WM) may be implicated in the etiology and maintenance of
depression. However, few studies have examined the effects of processing relevant
and irrelevant emotional stimuli on WM performance in depressed adolescents. In
the current study, depressed adolescents (n = 27) and healthy adolescents (n =
49) completed two versions of an emotional n-back task: a low WM load (0-back)
task and a high WM load (2-back) task. In the emotion-relevant condition
participants were asked to attend to the emotional expression of an angry, happy,
or neutral face, whereas in the emotion-irrelevant condition participants were
asked to attend to the gender of the face. The results showed a WM improvement
for happy faces in the emotion-relevant condition and a WM impairment for happy
faces in the emotion-irrelevant condition for healthy adolescents but not for
depressed adolescents. No biases toward angry faces were found. These results
demonstrate that depressed adolescents do not show a preferential processing of
angry faces but rather fail to show a positivity bias as seen in healthy
adolescents. This supports the theoretical notion that a depressive disorder is
characterized by a blunted reactivity toward positive information and may provide
new insights into the underlying mechanisms of youth depression.
PMID- 29342447
TI - Design, synthesis and anticancer studies of novel aminobenzazolyl pyrimidines as
tyrosine kinase inhibitors.
AB - Abnormal signalling from the Protein tyrosine kinases (PTKs) like receptor
tyrosine kinases and intracellular tyrosine kinases can lead to diseases such as
cancer especially non-small cell lung cancer, chronic myeloid leukaemia and
gastrointestinal stromal tumours. Various Protein tyrosine kinase inhibitors are
available but face poor bioavailability, severe toxicities and recent cases of
drug-resistant cancers prompts for development of better drug molecules. In this
study we report the design and development of a novel Protein Tyrosine Kinase
(PTK) inhibitor on the basis of pharmacophore modelling. Compound 2
(benzo[d]oxazol-2-ylamino)-N-(2-chloro-4-fluorophenyl)-4-methyl-6-(3-nitrophenyl)
pyrimidine-5-carboxamide 31 was obtained containing essential pharmacophore
structural features. This compound exhibited highest activity against leukaemia
cell line (RPMI-8226) at 0.7244 uM, renal cancer cell line (A498) at 0.8511 uM
and prostate cancer cell line (PC-3) at 0.7932 uM on the NCI five dose assay
test. The PTK assay provides promising activity at IC50 of 0.07 uM in the human
breast cancer cell line MDA-MB-468. Compound 31 had good intermolecular
interaction with PTK in the molecular docking studies, this ligand-enzyme complex
was found to stable in the MM-PBSA study over 100 ns. It had 54.22% oral
bioavailability with Tmax of 0.60 h which is higher compared to the dasatinib
with bioavailability and Tmax of 14-34% and 1-1.42 h respectively. Anticancer
action of 31 was found to be impressive in pharmacokinetic studies making it a
potential lead molecule.
PMID- 29342448
TI - Generation of induced pluripotent stem cell line, CSSi002-A (2851), from a
patient with juvenile Huntington Disease.
AB - Huntington Disease (HD) is an autosomal dominant disorder characterized by motor,
cognitive and behavioral features caused by a CAG expansion in the HTT gene
beyond 35 repeats. The juvenile form (JHD) may begin before the age of 20years
and is associated with expanded alleles as long as 60 or more CAG repeats. In
this study, induced pluripotent stem cells were generated from skin fibroblasts
of a 8-year-old child carrying a large size mutation of 84 CAG repeats in the HTT
gene. HD appeared at age 3 with mixed psychiatric (i.e. autistic spectrum
disorder) and motor (i.e. dystonia) manifestations.
PMID- 29342449
TI - Increased Use of Adrenaline in the Management of Childhood Anaphylaxis Over the
Last Decade.
AB - BACKGROUND: We recently determined that allergy training programs have improved
physician recognition and diagnosis of pediatric anaphylaxis in the last decade.
OBJECTIVE: To investigate for changes in management, in particular the
appropriate use of adrenaline for the treatment of anaphylaxis in a tertiary
pediatric emergency department (PED). METHODS: We conducted a retrospective case
note study including children aged 0 to 16 years coded and verified for
anaphylaxis comparing cases in years 2003/2004 with 2012. This included
standardized information on clinical presentation, demographic characteristics,
vital signs, mode of transport, and management of anaphylaxis including the use
of adrenaline and/or adjunct therapy. Follow-up management plans were also
recorded. RESULTS: In 2003/2004, a total of 92 cases were coded and verified for
anaphylaxis from 83,832 PED presentations compared with 159 cases from 71,822 PED
presentations in 2012. A significantly higher proportion of cases were
appropriately managed with adrenaline in 2012 compared with 2003/2004, when
intensive training programs had not yet been introduced (P = .03). Vital signs
were more frequently documented in 2012 (P < .001) than in 2003/2004, and there
was significantly less administration of other medications (corticosteroids,
bronchodilators, and antihistamines) (P < .05). Also, changes in discharge
management occurred with an improved dispensing/prescription of adrenaline
autoinjectors and more frequent follow-up arrangement with specialist allergy
services (P < .001). CONCLUSIONS: There was a significant improvement in the
management of anaphylaxis over this 10-year period. This change was observed
after the introduction of intensified physician training programs in which
anaphylaxis management was a key component highlighting the importance of
cooperation between pediatric emergency and allergy services.
PMID- 29342450
TI - Occupational allergic respiratory disease (rinoconjunctivitis and asthma) in a
cheese factory worker.
PMID- 29342451
TI - Decadal Changes in the Edible Supply of Seafood and Methylmercury Exposure in the
United States.
AB - BACKGROUND: Methylmercury (MeHg) exposure is associated with adverse effects on
neurodevelopment and cardiovascular health. Previous work indicates most MeHg is
from marine fish sold in the commercial market, but does not fully resolve supply
regions globally. This information is critical for linking changes in
environmental MeHg levels to human exposure in the U.S. population. OBJECTIVES:
We used available data to estimate the geographic origins of seafood consumed in
the United States (major ocean basins, coastal fisheries, aquaculture,
freshwater) and how shifts in edible supply affected MeHg exposures between 2000
2002 and 2010-2012. METHODS: Source regions for edible seafood and MeHg exposure
in the United States were characterized from national and international landing,
export and import data from the Food and Agricultural Organization of the United
Nations and the U.S. National Marine Fisheries Service. RESULTS: Our analysis
suggests 37% of U.S. population-wide MeHg exposure is from mainly domestic
coastal systems and 45% from open ocean ecosystems. We estimate that the Pacific
Ocean alone supplies more than half of total MeHg exposure. Aquaculture and
freshwater fisheries together account for an estimated 18% of total MeHg intake.
Shifts in seafood types and supply regions between 2000-2002 and 2010-2012
reflect changes in consumer preferences (e.g., away from canned light meat tuna),
global ecosystem shifts (e.g., northern migration of cod stocks), and increasing
supply from aquaculture (e.g., shrimp and salmon). CONCLUSION: Our findings
indicate global actions that reduce anthropogenic Hg emissions will be beneficial
for U.S. seafood consumers because open ocean ecosystems supply a large fraction
of their MeHg exposure. However, our estimates suggest that domestic actions can
provide the greatest benefit for coastal seafood consumers.
https://doi.org/10.1289/EHP2644.
PMID- 29342452
TI - Estimated Effect of Temperature on Years of Life Lost: A Retrospective Time
Series Study of Low-, Middle-, and High-Income Regions.
AB - BACKGROUND: Numerous studies have reported a strong association between
temperature and mortality. Additional insights can be gained from investigating
the effects of temperature on years of life lost (YLL), considering the life
expectancy at the time of death. OBJECTIVES: The goal of this work was to assess
the association between temperature and YLL at seven low-, middle-, and high
income sites. METHODS: We obtained meteorological and population data for at
least nine years from four Health and Demographic Surveillance Sites in Kenya
(western Kenya, Nairobi), Burkina Faso (Nouna), and India (Vadu), as well as data
from cities in the United States (Philadelphia, Phoenix) and Sweden (Stockholm).
A distributed lag nonlinear model was used to estimate the association of daily
maximum temperature and daily YLL, lagged 0-14 d. The reference value was set for
each site at the temperature with the lowest YLL. RESULTS: Generally, YLL
increased with higher temperature, starting day 0. In Nouna, the hottest
location, with a minimum YLL temperature at the first percentile, YLL increased
consistently with higher temperatures. In Vadu, YLL increased in association with
heat, whereas in Nairobi, YLL increased in association with both low and high
temperatures. Associations with cold and heat were evident for Phoenix (stronger
for heat), Stockholm, and Philadelphia (both stronger for cold). Patterns of
associations with mortality were generally similar to those with YLL.
CONCLUSIONS: Both high and low temperatures are associated with YLL in high-,
middle-, and low-income countries. Policy guidance and health adaptation measures
might be improved with more comprehensive indicators of the health burden of high
and low temperatures such as YLL. https://doi.org/10.1289/EHP1745.
PMID- 29342454
TI - Sodium Trimetaphosphate as a Novel Strategy for Matrix Metalloproteinase
Inhibition and Dentin Remineralization.
AB - The effect of sodium trimetaphosphate (STMP) as an antiproteolytic and
remineralizing agent on demineralized dentin was evaluated in vitro. The
inhibitory potential of STMP at 0.5, 1.5, 3.5, and 5% against recombinant matrix
metalloproteinases (MMPs) MMPs-2 and -9 was assessed by zymography. To
investigate its remineralization potential, 40 bovine root specimens were
obtained and subjected to a demineralization protocol to produce caries-like
dentin lesions. After that, dentin surfaces were divided into 3 areas: (1)
mineralized (no treatment); (2) demineralized; and (3) demineralized/treated with
STMP and submitted to a pH-cycling associated or not with STMP (1.5, 3.5, or 5%
STMP, 10 min of treatment). After that, superficial hardness (SH) and cross
sectional hardness (CSH) were determined. Polarized light microscopy (PLM) was
used to qualitatively evaluate mineralization within the caries-like lesions. The
zymographic analysis showed that STMP solution is a potent inhibitor of the
gelatinolytic activity of MMPs-2 and -9 depending on the dose, since the lowest
concentration (0.5%) partially inhibited the enzyme activity, while the higher
concentrations completely inhibited enzyme activity. Regarding remineralization
effect, only 1.5% STMP solution enhanced both the SH and CSH. PLM showed that the
area treated with 1.5% STMP presented similar birefringence as mineralized sound
dentin. In conclusion, 1.5% STMP solution is effective as an antiproteolytic
agent against MMPs and promotes dentin remineralization.
PMID- 29342453
TI - Fine Particulate Air Pollution and the Expression of microRNAs and Circulating
Cytokines Relevant to Inflammation, Coagulation, and Vasoconstriction.
AB - BACKGROUND: MicroRNAs (miRNAs) are a key factor in epigenetic regulation of gene
expression, but miRNA responses to fine particulate matter (PM2.5) air pollution
and their potential contribution to cardiovascular effects of PM2.5 are unknown.
OBJECTIVE: We explored the potential influence of PM2.5 on the expression of
selected cytokines relevant to systemic inflammation, coagulation, and
vasoconstriction, and on miRNAs that may regulate their expression. METHODS: We
designed a double-blind, randomized crossover study in which true and sham air
purifiers were used to expose 55 healthy young adult students in Shanghai, China,
to reduced or ambient levels of indoor PM2.5 during two-week periods, and we
measured the expression (mRNA and protein) of 10 serum cytokines, and miRNAs that
target them, after each intervention period. We used linear mixed-effect models
to estimate associations of the intervention, and time-weighted personal PM2.5
exposures, with the cytokines, mRNA, and miRNAs; we also explored potential
mediation by miRNAs. RESULTS: The findings were generally consistent for
associations with the intervention and for associations with an interquartile
range increase in time-weighted PM2.5. Specifically, higher PM2.5 exposure was
positively associated with the expression (mRNA, protein, or both) of interleukin
1 (encoded by IL1), IL6, tumor necrosis factor (encoded by TNF), toll-like
receptor 2 (encoded by TLR2), coagulation factor 3 (encoded by F3), and
endothelin 1 (encoded by EDN1), and was negatively associated with miRNAs (miR-21
5p, miR-187-3p, miR-146a-5p, miR-1-3p, and miR-199a-5p) predicted to target mRNAs
of IL1, TNF, TLR2, and EDN1. CONCLUSIONS: Our findings require confirmation but
suggest that effects of PM2.5 on cardiovascular diseases may be related to acute
effects on cytokine expression, which may be partly mediated through effects of
PM2.5 on miRNAs that regulate cytokine expression.
https://doi.org/10.1289/EHP1447.
PMID- 29342455
TI - Endoscopic Full-Thickness Resection of a Colonic Lateral Spreading Tumor.
AB - The Full-Thickness Resection Device (FTRD; Ovesco Endoscopy, Tubingen, Germany)
combines endoscopic full-thickness resection (EFTR) of gastrointestinal lesions
with closure and cutting of the tissue in one integrated procedure. It provides
en-bloc resection with an integral wall specimen for histopathological
evaluation. This resection technique is partially filling of the gaps between the
current procedures of choice in endoscopy (endoscopic mucosal resection and
endoscopic submucosal dissection) and surgery. We present the case of an EFTR
procedure performed for a periappendicular lateral spreading tumor.
PMID- 29342456
TI - Correlation between Resection Margin and Disease Recurrence with a Restricted
Cubic Spline Model in Patients with Resected Hepatocellular Carcinoma.
AB - BACKGROUND: The relationship between resection margin (RM) and recurrence of
resected hepatocellular carcinoma (HCC) is unclear. METHODS: We reviewed clinical
data for 419 patients with HCC. The oncologic outcomes were compared between 2
groups of patients classified according to the inflexion point of the restricted
cubic spline plot. RESULTS: The patients were divided according to an RM of <1 cm
(n = 233; narrow RM group) or >=1 cm (n = 186; wide RM group). The 5-year
recurrence-free survival (RFS) rate was lower (34.8 vs. 43.8%, p = 0.042) and
recurrence near the resection site was more frequent (4.7 vs. 0%, p = 0.010) in
the narrow RM group. Patients with multiple lesions, or prior transarterial
chemoembolization (TACE) or radiofrequency ablation (RFA) were excluded from
subgroup analyses. In patients with a 2-5 cm HCC, the 5-year RFS was greater in
the wide RM group (54.4 vs. 32.5%, p = 0.036). Narrow RM (hazard ratio 1.750, 95%
CI 1.029-2.976, p = 0.039) was independently associated with disease recurrence.
CONCLUSION: In patients with a single 2-5 cm HCC without prior TACE/RFA, an RM of
>=1 cm was associated with lower risk of recurrence after liver resection.
PMID- 29342457
TI - The von Hippel-Lindau Gene Is Required to Maintain Renal Proximal Tubule and
Glomerulus Integrity in Zebrafish Larvae.
AB - BACKGROUND: von Hippel-Lindau (VHL) disease is characterized by the development
of benign and malignant tumours in many organ systems, including renal cysts and
clear cell renal cell carcinoma. It is not completely understood what underlies
the development of renal pathology, and the use of murine Vhl models has been
challenging due to limitations in disease conservation. We previously described a
zebrafish model bearing inactivating mutations in the orthologue of the human VHL
gene. METHODS: We used histopathological and functional assays to investigate the
pronephric and glomerular developmental defects in vhl mutant zebrafish,
supported by human cell culture assays. RESULTS: Here, we report that vhl is
required to maintain pronephric tubule and glomerulus integrity in zebrafish
embryos. vhl mutant glomeruli are enlarged, cxcr4a+ capillary loops are dilated
and the Bowman space is widened. While we did not observe pronephric cysts, the
cells of the proximal convoluted and anterior proximal straight tubule are
enlarged, periodic acid schiff (PAS) and Oil Red O positive, and display a clear
cytoplasm after hematoxylin and eosine staining. Ultrastructural analysis showed
the vhl-/- tubule to accumulate large numbers of vesicles of variable size and
electron density. Microinjection of the endocytic fluorescent marker AM1-43 in
zebrafish embryos revealed an accumulation of endocytic vesicles in the vhl
mutant pronephric tubule, which we can recapitulate in human cells lacking VHL.
CONCLUSIONS: Our data indicates that vhl is required to maintain pronephric
tubule and glomerulus integrity during zebrafish development, and suggests a role
for VHL in endocytic vesicle trafficking.
PMID- 29342458
TI - Glucocorticoids Modulate Th1 and Th2 Responses in Asthmatic Mouse Models by
Inhibition of Notch1 Signaling.
AB - BACKGROUND: Notch1 has been linked to the pathogenesis of asthma due to its
contribution on Th1/Th2 imbalance. gamma-Secretase inhibitor (GSI) acts as an
effective blocker of Notch1 signaling. Glucocorticoids (GCs) are the most
effective anti-inflammatory drugs for asthma. The present study investigated the
involvement of the Notch1 pathway in the anti-inflammatory effect of GCs and its
association with Th1/Th2 balance. METHODS: The asthma model was established in
BALB/c mice by sensitization with ovalbumin (OVA). Dexamethasone (DEX; 1 mg/kg)
and/or GSI (0.03 mg/kg) was orally or intranasally administrated. RESULTS:
Compared to the OVA-sensitized mice, the administration of DEX and/or GSI
significantly ameliorated the airway inflammation infiltration, goblet cell
metaplasia, and airway hyper-responsiveness. The expression of IL-4 and IL-13, as
well as the ratios of eosinophils and lymphocytes, were significantly decreased,
whereas IFN-gamma and IL-2 levels were significantly increased in bronchoalveolar
lavage fluid after the administration of DEX and GSI. The expressions of the
Notch1/NICD1 pathway were decreased after DEX and/or GSI administration in lung
tissues, especially in CD4+ T cells. Also, a reduction of GATA3 and elevation of
T-bet levels were correlated with the upregulation of Th1/Th2 ratios in lung
tissues. CONCLUSIONS: Through the inhibition of Notch1 signaling, both GSI and
GCs could regulate Th1/Th2 balance involved in allergic airway inflammation in
OVA-induced asthma.
PMID- 29342459
TI - Risk Factors and Clinical Features in Cashew Nut Oral Food Challenges.
AB - BACKGROUND: Cashew nuts (CN) are capable of causing severe allergic reactions.
However, little has been reported about the details of CN oral food challenges
(OFC). METHODS: CN-specific IgE (sIgE) levels were measured for 1 year in 66
patients who underwent an OFC with >3 g CN for diagnosis or confirmation of
tolerance acquisition between June 2006 and August 2014. We retrospectively
analyzed the OFC and patient background. RESULTS: The median (IQR) age of the 66
patients (48 boys/men and 18 girls/women) was 7.0 years (5.7-8.8). Twelve
patients (18.2%) had a positive OFC result; 6 of 8 (75%) patients with a history
of an immediate reaction to CN failed the OFC. Anaphylaxis was experienced by 5
of these 12 (42%) patients. A history of an immediate reaction to CN and the CN
sIgE levels were significantly different for patients with a positive or negative
OFC result (p < 0.01). Among patients without a previous immediate reaction to
CN, the 95% positive predictive value (PPV) for the CN sIgE level for a positive
OFC result was 66.1 kUA/L. CONCLUSIONS: A history of an immediate reaction to CN
and high CN sIgE were risk factors for a positive OFC result. The number of
positive OFC results was relatively low, but there was a high probability of
anaphylaxis. We should consider the indication of OFC carefully for patients with
a history of immediate reactions to CN and avoid OFC for patients without such a
history whose CN sIgE values are >66.1 kUA/L (95% PPV).
PMID- 29342460
TI - Role of the Frontal Sinus in Mediating Ocular Vestibular-Evoked Myogenic
Potentials by Bone Vibration Stimuli Applied to the Forehead.
AB - This study investigated ocular vestibular-evoked myogenic potential (oVEMP) tests
via Fpz and Fz taps to assess the role of the frontal sinus in mediating oVEMP
elicitation. Forty healthy subjects and 80 patients with Meniere disease (MD)
underwent a series of oVEMP tests via a minishaker tapping at the Fpz and Fz
sites in a randomized order. Response rates of oVEMP test via various tapping
sites were compared. Dimensions of the frontal sinus were measured via CT scan. A
significantly negative correlation between the age and height of the frontal
sinus was noted, and the cutoff age for discriminating present and absent Fpz
oVEMPs in MD patients was 52 years. Additionally, oVEMPs by Fpz tapping were more
efficiently presented in males than females, likely because of the greater
resonance by the larger height of the frontal sinus in males (3.88 +/- 0.68 cm)
than females (3.42 +/- 0.67 cm). In conclusion, the height of the frontal sinus
plays a role in mediating the elicitation of oVEMPs. The oVEMPs could be easily
elicited by the first-order bone vibration (Fpz/Fz tapping) coupled with the
second-order resonance effect (with a high extent of the frontal sinus). Thus,
initial tapping at the Fpz site is suggested. If it fails, try the Fz site for
screening the oVEMPs.
PMID- 29342461
TI - Mechanism of Periostin Production in Human Bronchial Smooth Muscle Cells.
AB - BACKGROUND: Asthma is a chronic airway inflammatory disease characterized by
airway remodeling, in which the bronchial smooth muscle (BSM) cells play an
important role. Periostin, a biomarker that reflects Th2-driven inflammatory
diseases such as asthma, may play an important role in the asthmatic airway.
Although periostin is mainly produced in airway epithelial cells and fibroblasts
after interleukin (IL)-13 stimulation, whether BSM cells produce periostin
remains unclear. Therefore, we investigated periostin production in BSM cells and
the mechanisms involved. METHODS: Human BSM cells were cultured, and the effect
of IL-13 stimulation on periostin production was evaluated using quantitative
polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). We
evaluated the phosphorylation of signal transducer and activator of transcription
factor 6 (STAT6), extracellular signal-regulated kinase (ERK)1/2, and Akt after
IL-13 stimulation. Furthermore, using ELISA, we evaluated the influence of
several phosphorylation inhibitors on periostin production. RESULTS: Periostin
mRNA expression increased in a dose- and time-dependent manner after IL-13
stimulation; periostin production was induced 24 and 48 h after stimulation. IL
13 stimulation induced the phosphorylation of STAT6, ERK1/2, and Akt. IL-13
induced periostin production was attenuated by inhibiting STAT6 phosphorylation
and strongly suppressed by inhibiting mitogen-activated protein kinase kinase 1/2
phosphorylation or phosphatidylinositol 3-kinase (PI3K) phosphorylation.
CONCLUSIONS: BSM cells produced periostin after IL-13 stimulation, via the
JAK/STAT6, ERK1/2, and PI3K/Akt pathways. Understanding the mechanism of
periostin production in BSM cells may help to clarify asthma pathogenesis.
PMID- 29342462
TI - Reference Values for Respiratory Muscle Strength in Children and Adolescents.
AB - BACKGROUND: Measurement of respiratory muscle function is important in the
diagnosis of respiratory muscle disease, respiratory failure, to assess the
impact of chronic diseases, and/or to evaluate respiratory muscle function after
treatment. OBJECTIVES: To establish reference values for maximal inspiratory and
expiratory pressure, and the tension-time index at rest in healthy children and
adolescents aged 8-19 years, as well as to present sex- and age-related reference
centiles normalized for demographic and anthropometric determinants. METHODS: In
this cross-sectional observational study, demographic, anthropometric, and
spirometric data were assessed, as well as data on respiratory muscle strength
(PImax and PEmax) and work of breathing at rest (TT0.1), in a total of 251
children (117 boys and 134 girls; mean age 13.4 +/- 2.9 years). Reference values
are presented as reference centiles developed by use of the lambda, mu, sigma
method. RESULTS: Boys had significantly higher PImax and PEmax values. Next to
sex and age, fat-free mass appeared to be an important predictor of respiratory
muscle strength. Reference centiles demonstrated a slight, almost linear increase
in PImax with age in boys, and a less steep increase with age in girls. TT0.1
values did not differ between boys and girls and decreased linearly with age.
CONCLUSION: This study provides reference values for respiratory muscle strength
and work of breathing at rest. In addition to sex and age, fat-free mass was
found to be an important predictor of respiratory muscle strength in boys and
girls.
PMID- 29342463
TI - Sensation of Cold during the Ice Water Test Corresponds to the Perception of Pain
during Botulinum Toxin Bladder Wall Injections.
AB - AIMS: To investigate the association of bladder cold sensation (BCS) during the
ice water test (IWT) and pain perception when botulinum toxin injections (BTI)
are administered into the bladder wall. MATERIAL AND METHODS: In 86 patients with
idiopathic overactive bladder, the BCS during the IWT was investigated. Patients
were divided into 2 groups: with and without BCS. During subsequent
administration of BTI, the number of perceived and painful injections as well as
the pain levels on a 0-100 pain scale were compared in both groups using Student
t test. RESULTS: Thirty-five patients reported a BCS, while 51 did not. After 10
BTI, the mean number of perceived injections was 7.9 in patients with and 2.4 in
patients without BCS (p < 0.0001). The mean number of painful injections was 5.4
in patients with BCS and 4.3 in patients without (p < 0.001). Mean levels on a 0
100 pain scale were 33.7 in patients with and 17.8 in patients without cold
sensation (p < 0.0001). CONCLUSION: The association of BCS during the IWT and
pain to during BTI may implicate that the perceptions of cold and pain in the
urinary bladder may use similar receptors and neuronal pathways.
PMID- 29342464
TI - Risk Factors for Intraoperative Hypocapnia in Pediatric Neurosurgical Patients: A
Retrospective Cohort Study.
AB - BACKGROUND: Hypocapnia has been associated with an increased risk and adverse
outcomes in the injured brain. This study aimed to identify risk factors of
intraoperative hypocapnia in pediatric neurosurgical patients when tidal volumes
and respiratory rates were determined based on their weight and age,
respectively. METHODS: Electronic medical records of pediatric patients (<=18
years) who underwent neurosurgery from December 2014 to January 2016 were
retrospectively reviewed. Minute ventilation was fixed according to each
patient's weight and age. Hypocapnia was defined as arterial partial pressure of
carbon dioxide <35 mm Hg from intraoperative arterial blood gas analysis.
Patients were divided into hypocapnia and nonhypocapnia groups. Risk factors for
intraoperative hypocapnia were found using univariable and multivariable logistic
regression analyses. RESULTS: Of the 333 pediatric patients analyzed, 101 (30%)
and 232 (70%) were included in the hypocapnia and nonhypocapnia groups,
respectively. There was no difference in the minute ventilation between the two
groups. The hypocapnia group had more patients taking valproate (8.9 vs. 2.2%; p
= 0.008; OR, 4.441; 95% CI, 1.449-13.61) and carbonic anhydrase inhibitors (7.9
vs. 2.2%; p = 0.018; OR, 3.905; 95% CI, 1.245-12.25). An operation for
hydrocephalus was more commonly performed in the hypocapnia group (26.7 vs.
15.9%; p = 0.017; OR, 1.923; 95% CI, 1.094-3.379). In the multivariable
regression analysis, valproate (OR, 3.939; 95% CI, 1.250-12.41; p = 0.019),
carbonic anhydrase inhibitor (OR, 3.345; 95% CI, 1.029-10.88; p = 0.045), and
operation for hydrocephalus (OR, 1.838; 95% CI, 1.032-3.272; p = 0.039) were
independent risk factors for intraoperative hypocapnia. CONCLUSIONS: Pediatric
patients taking valproate and carbonic anhydrase inhibitors and who were
scheduled for surgery of hydrocephalus were at risk of developing intraoperative
hypocapnia during neurosurgery, a finding warning the surgeon that a conventional
ventilatory strategy would endanger these patients.
PMID- 29342466
TI - Deep Vein Thrombosis: A Rare Cause of Acute Testicular Pain. Case Report:
Literature Review.
AB - INTRODUCTION: Thrombosis is defined as the formation of a clot in a blood vessel
that obstructs the flow of blood to the peripheral tissues. The incidence of
thromboembolic disease ranges from 0.7 to 1.2% within urology. CASE REPORT: A 40
year-old warehouse worker male presented to the emergency department with
worsening of a month's lasting scrotal pain. Physical examination showed the
presence of an enlarged and painful left testicle with no other findings. Right
testicle, penis and abdominal examination showed no abnormalities whatsoever.
Bilateral varicocele with a partial thrombosis of the left one associated with
left inguinal hernia was diagnosed by performing an urgent testicular ultrasound
test. Conservative treatment was first given. However, since pain was not
relieved, surgery was indicated with left varicocelectomy and a left inguinal
hernia repair procedure leading to complete symptoms control and normal
testicular flow in the control Doppler ultrasound study 2 months after the
surgery. CONCLUSION: Spontaneous thrombosis of the pampiniform plexus is a rare
entity where the management remains controversial. The clinical case we report
here shows that surgery may be considered an effective option.
PMID- 29342465
TI - De Novo Bladder Urothelial Neoplasm in Renal Transplant Recipients: A
Retrospective, Multicentered Study.
AB - BACKGROUND AND OBJECTIVES: Renal transplant recipients (RTRs) have a 2- to 7-fold
risk of developing a neoplasm compared to general population. Bladder urothelial
neoplasms in this cohort has an incidence of 0.4-2%. Many reports describe a more
aggressive behavior. The objective of this study is to describe oncologic
characteristics of bladder urothelial neoplasms in RTRs and to evaluate its
recurrence, progression, and survival rates. METHODS: A retrospective
multicentered study was performed evaluating all de novo bladder urothelial
neoplasms cases in RTRs from 1988 to 2014. Descriptive statistical analysis and
evaluation of recurrence, progression, and survival rates were performed.
RESULTS: A total of 28 de novo bladder transitional cell carcinomas (TCCs) were
identified (incidence rate 0.64%). Cancer-specific survival rates were 100, 75,
and 70% after 1, 5, and 10 years, respectively. Age at diagnosis superior to 60
years was found to be a statistically significant variable for recurrence risk.
Progression rate was 14%. Presence of CIS was significantly associated with
progression. All cancer-specific deaths were in the high-risk group and all were
progressions from non-muscle invasive to muscle invasive bladder cancer.
CONCLUSIONS: Bladder urothelial neoplasms following renal transplant is
associated with a trend toward worst prognosis. Early aggressive treatments, such
as early radical cystectomy, might be advisable to reduce cancer-specific deaths.
PMID- 29342467
TI - Boiling and Pressure Cooking Impact on IgE Reactivity of Soybean Allergens.
AB - BACKGROUND: Soybean is one of the 8 foods that causes the most significant rate
of food allergies in the USA and Europe. Thermal processing may impact on the
allergenic potential of certain foods. We aimed to investigate modifications of
the IgE-binding properties of soybean proteins due to processing methods that
have been previously found to impact on the allergenicity of legumes such as
peanut. METHODS: Soybean seeds were subjected to different thermal processing
treatments. To evaluate their impact on the IgE-binding capacity of soybean
proteins, individual sera from 25 patients sensitized to soybean were used in in
vitro immunoassays. Detection of specific soybean allergens in untreated and
treated samples was carried out with specific monoclonal and polyclonal
antibodies. In vivo studies of skin prick testing (SPT) were also performed.
RESULTS: The IgE reactivity of soybean was resistant to boiling up to 30 min, and
this treatment had a higher impact when applied for 60 min. Treatment that
combined heat and pressure produced a fragmentation of proteins in both soluble
and insoluble fractions that went along with a decreased capacity to bind IgE and
reduced the SPT wheal size. However, allergens such as 7S globulins survived this
treatment. CONCLUSIONS: Thermal-processing methods able to attenuate the capacity
of soybean proteins to bind IgE may contribute to the improvement of food safety
and could constitute a potential strategy for the induction of tolerance to
soybean.
PMID- 29342468
TI - The Role of History of Gastro-Duodenal Ulcer in Patients with Upper
Gastrointestinal Bleeding.
AB - BACKGROUND: Some scoring systems have been introduced to predict the need for
performing urgent endoscopy in patients with upper gastrointestinal bleeding
(UGIB). However, in an emergency situation, this intervention is insufficient and
cannot easily provide the required treatment. AIM: To identify new risk factors
that can predict the need for endoscopic intervention (EI) in UGIB patients.
METHODS: This is a retrospective cross-sectional study. Patients with UGIB
admitted from April 2011 to August 2014 were included. The proportion of cases
requiring EI and clinical factors (age, gender, antiplatelet/anticoagulant
therapy, history of gastro-duodenal ulcer (GDU), systolic blood pressure, heart
rate, hemoglobin, mean corpuscular volume, blood urea nitrogen-creatinine ratio
(BUN/Cr ratio), prothrombin time-international normalized ratio, and Glasgow
Blatchford Score (GBS) were analyzed using logistic regression models. RESULT: Of
378 patients who were included in this study, 180 were found to be with GDU. The
proportion of cases requiring EI was significantly higher in those with GDU than
in other causes except variceal bleeding (53.5 vs. 37.0%, p < 0.01). Multivariate
analysis revealed that a history of GDU was an independent risk factor (OR 1.78,
95% CI 1.06-3.00) in addition to BUN/Cr ratio (OR 1.02, 95% CI 1.00-1.03) and GBS
(OR 1.19, 95% CI 1.08-1.33). CONCLUSION: A history of GDU was an independent risk
factor for predicting the need for EI in UGIB in addition to BUN/Cr ratio and
GBS.
PMID- 29342469
TI - The 2017 Update of the German Clinical Guideline on Epidemiology, Diagnostics,
Therapy, Prevention, and Management of Uncomplicated Urinary Tract Infections in
Adult Patients: Part 1.
AB - OBJECTIVES: We aimed to update the 2010 evidence- and consensus-based national
clinical guideline on the diagnosis and management of uncomplicated urinary tract
infections (UTIs) in adult patients. MATERIALS AND METHODS: An interdisciplinary
group consisting of 17 representatives of 12 medical societies and a patient
representative was formed. Systematic literature searches were conducted in
MEDLINE, -EMBASE, and the Cochrane Library to identify literature published in
2010-2015. RESULTS: We provide 75 recommendations and 68 statements in the
updated evidence- and consensus-based national clinical guideline. The
diagnostics part covers practical recommendations on cystitis and pyelonephritis
for each defined patient group. Clinical examinations, as well as laboratory
testing and microbiological pathogen assessment, are addressed. CONCLUSION: In
accordance with the global antibiotic stewardship initiative and considering new
insights in scientific research, we updated our German clinical UTI guideline to
promote a responsible antibiotic use and to give clear hands-on recommendations
for the diagnosis and management of UTIs in adults in Germany for healthcare
providers and patients.
PMID- 29342470
TI - "Nested Type" Bladder Cancer: Myth or Reality?
PMID- 29342471
TI - Extra-articular manifestations and burden of disease in patients with
radiographic and non-radiographic axial spondyloarthritis.
AB - OBJECTIVE: Although the prevalence of peripheral and extra-articular disease in
ankylosing spondylitis (AS) has been assessed in many studies, data on non
radiographic axial spondyloarthritis (nr-axSpA) is scanty. The aim of this study
was first, to compare radiographic-axSpA/AS (r-axSpA/AS) and nr-axSpA concerning
peripheral arthritis and extra-articular manifestations (EAMs), and second, to
assess potential differences between patient subgroups with or without EAMs
regarding disease burden. METHODS: Data was extracted from our single center
axSpA database. Patients having at least one of the EAMs (uveitis and/or
inflammatory bowel disease (IBD) and/or psoriasis) were compared to those who did
not have EAMs. Patients' clinical data including disease activity, functional and
psychological status, physical limitations, quality of life (QoL) and magnetic
resonance imaging of sacroiliac joints (SIJ MR) were evaluated. RESULTS: Patients
with nr-axSpA (n=193) were younger, had female predominance, better functional
and physical status, higher frequency of bone edema in SIJ MR and peripheral
arthritis but similar QoL, prevalence of HLA B27 and EAMs compared to r-axSpA/AS
(n=352). The prevalence of current or ever uveitis (14.5 vs 15.3%, p=0.791),
psoriasis (6.2 vs 5.4%, p=0.689) or IBD (4.1 vs 3.4%, p=0.663) in nr-axSpA and r
axSpA/AS were similar. In both subgroup of patients, EAMs positive and negative
patients had similar functional status and QoL, as well as disease activity and
laboratory parameters. CONCLUSION: Patients with nr-axSpA and r-axSpA/AS have
similar prevalence of EAMs and clinical burden of disease. Having EAMs does not
have a major influence on clinical parameters and patient reported outcome
measures in nr-axSpA and r-axSpA/AS.
PMID- 29342472
TI - Standard practice aiming clinical excellence in rheumatology.
PMID- 29342473
TI - Effectiveness of early adalimumab therapy in psoriatic arthritis patients from
Reuma.pt - EARLY PsA.
AB - Objective To compare outcomes in psoriatic arthritis (PsA) patients initiating
adalimumab (ADA), with short- and long-term disease duration and to evaluate the
potential effect of concomitant conventional synthetic disease-modifying
antirheumatic drugs (csDMARD) or glucocorticoids. Methods Analyses included adult
PsA patients registered in the Rheumatic Diseases Portuguese Register (Reuma.pt)
between June 2008-June 2016 who received ADA for >=3 months. Psoriatic Arthritis
Response Criteria (PsARC) response, tender and swollen joint count, inflammatory
parameters, patient (PtGA) and physician global assessment (PhGA), Disease
Activity Score-28 joints (DAS28), and Health Assessment Questionnaire Disability
Index (HAQ-DI) were compared between patients with <5 years of disease (early
PsA) and those with >=5 years of disease duration (late PsA). Time to achieving
PsARC response was estimated using the Kaplan-Meier method. Results Of 135 PsA
patients treated with ADA, 126 had information on disease duration (earlyPsA,
n=41). PsARC response was achieved by 72.9% of the patients (88.0% early PsA vs
62.2% late PsA; P=0.022) after 3 months and by 85.4% after 24 months (100% early
PsA vs 75.9% late PsA; P=0.044). Early PsA patients achieved significantly less
painful joints (2.7 vs 6.7, p=0.006), lower mean C-reactive protein (0.5 mg/dL vs
1.3 mg/dL; P=0.011), and PhGA (18.3 vs 28.1; P=0.020) at 3 months. In the long
term, early PsA patients also had fewer swollen joints (0.3 vs 1.7; P=0.030) and
lower PhGA (6.3 vs 21.9; P<0.001), C-reactive protein (0.4 mg/dL vs 1.0 mg/dL;
P=0.026), and DAS28 (2.2 vs 3.2; P=0.030). HAQ-DI decreased in both groups
reaching a mean value at 24 months of 0.4 and 0.8 (P=ns) in early and late PsA,
respectively. Early PsA patients obtained PsARC response more rapidly than late
PsA (3.8 and 7.4 months, respectively; P=0.008). Concomitant csDMARDs showed
clinical benefit (2-year PsARC response, 88.3% vs 60.0%; P=0.044). Concomitant
glucocorticoids had no effect on PsARC response over 2 years of follow-up.
Persistence on ADA was similar in both groups. Conclusion Early PsA patients had
a greater chance of improvement after ADA therapy and better functional outcome,
and achieved PsARC response more rapidly than late PsA. In this cohort,
comedication with csDMARDs was beneficial over 2 years.
PMID- 29342474
TI - The importance of quality of life for work outcomes in patients with ankylosing
spondylitis - a cross-sectional study.
AB - AIMS: Work impairment is one of the most important exploration and one of the
aims of rheumatologists. We aimed to determine the risk factors for employment
state and predictive factors of work outcomes using multi-dimensional measures in
patients with ankylosing spondylitis (AS) in this comprehensive study. METHODS:
One hundred patients with AS (31 females and 69 males) were included into this
study. Demographic properties, local factors, disease activity (BASDAI),
functionality (BASFI), spinal mobility (BASMI), radiologic stage (BASRI), quality
of life (AS-QoL), cardiopulmonary involvement, exercise stress test and work
outcomes were investigated and compared in employed and un-employed patients. The
work instability scale (AS-WIS) and work productivity activity impairment scale
(WPAI:SpA) were selected as work outcomes. The predictive factors were analyzed
using multiple stepwise linear regressions. MAJOR RESULTS: Thirty-two patients
(mean age: 42,6+/-11.7) were unemployed and the risk factors for unemployment
state were female sex, lower annual income level, and older age. Work disability
was detected only in 5% of patients. Decreased chest mobility (beta: -0.398, p:
<0.001), low annual income level (beta:-0.291, p:<0.001), higher co-morbidities
(beta:0.237, p:0.004), poorer AS-QoL (beta:0.238, p:0,012) and poorer AS-WIS
score (beta:0.289, p: 0,004) were the predictors of work impairment. The
predictive factors for work instability were higher work impairment (beta:0.533,
p<0.001) and poorer AS-QoL (beta: 0.426, p<0.001) scores. CONCLUSIONS: Employment
state mainly depends on contextual factors including male sex, higher income, and
younger age. Socioeconomic factors as well as clinical data such as QoL were
predictive for work productivity. Poorer AS-QoL was also a predictive factor for
work instability.We suggested effective interventions to improve clinical and
economic status in patients with AS.
PMID- 29342475
TI - Sexual dysfunction in systemic lupus erythematosus patients.
PMID- 29342476
TI - [Determinants of the Distance-Related Choice of Physician Using the Example of
Patients with Psoriasis and Chronic Wounds].
AB - STUDY AIM: There is only little knowledge about the influence of individual and
sociodemographic characteristics determining patients' choice of their
physicians. Furthermore, the role of patients' mobility is not clear. The primary
aim of this study was the analysis of patients' decision patterns when choosing a
physician. Patients' mobility as well as sociodemographic aspects were included
in the analysis. METHODS: A multicenter cross-sectional study was conducted. Data
were assessed at office-based dermatologists and at the University Medical Center
Hamburg-Eppendorf. Patients with psoriasis and chronic wounds were interviewed
about their behaviour when choosing a physician. Data analysis was performed
using descriptive and multivariate methods. RESULTS: Data on 309 patients (50.5%
male, mean age 58.3 years) were analysed. 211 patients were recruited at the
outpatient unit of the university clinic, 98 at office-based physicians. The
decision to visit a physician is primarily influenced by the physicians'
competence, his range of service and the physician-patient relationship. The
perspective of a better therapy as well as worsening of quality of life are
responsible for a higher motivation to travel a longer distance to the physician.
CONCLUSION: The results show a complex behaviour pattern of patients when
choosing a physician. The physician's competence and his range of services are
crucial for the patients' decision. The results also show that patients are
willing to travel longer distances than necessary.
PMID- 29342477
TI - [New Challenges: Diagnosis of Brain Death in Newborn, Children and Adolescents].
AB - BACKGROUND: According to the current update of the German guideline on brain
death (BD), participation of paediatricians is now mandatory for the examination
of BD in patients younger than 14 years. The present analysis focuses on the
previous practice and highlights the challenges that arise from the current
update. METHODS: Retrospective evaluation of the patient registry of the German
organ procurement organisation (north-eastern bureau) between January, 2001 and
December, 2010 with specified paediatric age groups according to the 4th update
of the German guideline on BD from the 1st of July 2015. RESULTS: 133 patients (0
17 years) received at least one BD examination. Secondary brain damage was most
frequent within the first 6 months of life whereas traumatic and other causes of
primary brain damage were predominantly observed thereafter. The number of
patients who received BD examination by paediatricians or were treated on
neonatal/paediatric intensive care units declined with increasing age. In more
than two-third of all paediatric patients, no paediatrician was involved in BD
diagnostics. DISCUSSION: After enforcement of the 4th update of the German
guideline on BD, the participation of qualified paediatric physicians must be
increased significantly compared to previous practice. Advancements in the
specialist training of paediatric physicians, adjustments in patient-centered
paediatric care and interdisciplinary diagnostic teams may be solutions to meet
this demand.
PMID- 29342478
TI - Design and Implementation of a Visual Analytics Electronic Antibiogram within an
Electronic Health Record System at a Tertiary Pediatric Hospital.
AB - BACKGROUND: Hospitals use antibiograms to guide optimal empiric antibiotic
therapy, reduce inappropriate antibiotic usage, and identify areas requiring
intervention by antimicrobial stewardship programs. Creating a hospital
antibiogram is a time-consuming manual process that is typically performed
annually. OBJECTIVE: We aimed to apply visual analytics software to electronic
health record (EHR) data to build an automated, electronic antibiogram ("e
antibiogram") that adheres to national guidelines and contains filters for
patient characteristics, thereby providing access to detailed, clinically
relevant, and up-to-date antibiotic susceptibility data. METHODS: We used visual
analytics software to develop a secure, EHR-linked, condition- and patient
specific e-antibiogram that supplies susceptibility maps for organisms and
antibiotics in a comprehensive report that is updated on a monthly basis.
Antimicrobial susceptibility data were grouped into nine clinical scenarios
according to the specimen source, hospital unit, and infection type. We
implemented the e-antibiogram within the EHR system at Children's Hospital of
Philadelphia, a tertiary pediatric hospital and analyzed e-antibiogram access
sessions from March 2016 to March 2017. RESULTS: The e-antibiogram was
implemented in the EHR with over 6,000 inpatient, 4,500 outpatient, and 3,900
emergency department isolates. The e-antibiogram provides access to rolling 12
month pathogen and susceptibility data that is updated on a monthly basis. E
antibiogram access sessions increased from an average of 261 sessions per month
during the first 3 months of the study to 345 sessions per month during the final
3 months. CONCLUSION: An e-antibiogram that was built and is updated using EHR
data and adheres to national guidelines is a feasible replacement for an annual,
static, manually compiled antibiogram. Future research will examine the impact of
the e-antibiogram on antibiotic prescribing patterns.
PMID- 29342479
TI - Time Spent on Dedicated Patient Care and Documentation Tasks Before and After the
Introduction of a Structured and Standardized Electronic Health Record.
AB - BACKGROUND: Physicians spend around 35% of their time documenting patient data.
They are concerned that adopting a structured and standardized electronic health
record (EHR) will lead to more time documenting and less time for patient care,
especially during consultations. OBJECTIVE: This study measures the effect of the
introduction of a structured and standardized EHR on documentation time and time
for dedicated patient care during outpatient consultations. METHODS: We measured
physicians' time spent on four task categories during outpatient consultations:
documentation, patient care, peer communication, and other activities. Physicians
covered various specialties from two university hospitals that jointly
implemented a structured and standardized EHR. Preimplementation, one hospital
used a legacy-EHR, and one primarily paper-based records. The same physicians
were observed 2 to 6 months before and 6 to 8 months after implementation.We
analyzed consultation duration, and percentage of time spent on each task
category. Differences in time distribution before and after implementation were
tested using multilevel linear regression. RESULTS: We observed 24 physicians
(162 hours, 439 consultations). We found no significant difference in
consultation duration or number of consultations per hour. In the legacy-EHR
center, we found the implementation associated with a significant decrease in
time spent on dedicated patient care (-8.5%). In contrast, in the previously
paper-based center, we found a significant increase in dedicated time spent on
documentation (8.3%) and decrease in time on combined patient care and
documentation (-4.6%). The effect on dedicated documentation time significantly
differed between centers. CONCLUSION: Implementation of a structured and
standardized EHR was associated with 8.5% decrease in time for dedicated patient
care during consultations in one center and 8.3% increase in dedicated
documentation time in another center. These results are in line with physicians'
concerns that the introduction of a structured and standardized EHR might lead to
more documentation burden and less time for dedicated patient care.
PMID- 29342480
TI - Phenolic Compounds as Arginase Inhibitors: New Insights Regarding Endothelial
Dysfunction Treatment.
AB - Endothelial dysfunction is characterised by the low bioavailability of nitric
oxide with a relevant negative impact on the nitric oxide/cGMP pathway. The loss
of nitric oxide/cGMP signaling may be caused by an increased arginase activity.
Plant-derived substances, especially polyphenols, are compounds that have the
potential to inhibit arginase activity and they may represent an attractive
therapeutic option to combat clinical outcomes related to endothelial
dysfunction. An extensive review was carried out using all available data
published in English in the Pubmed database, and without restriction regarding
the year of publication. Despite the increased number of new substances that have
been tested as arginase inhibitors, it is rare to find a compound that satisfies
all the toxicological criteria to be used in the development of a new drug. On
the other hand, recent data have shown that substances from plants have great
potential to be applied as arginase inhibitors, most of which are polyphenols. Of
the relevant mechanisms in this process, the inhibition of arginase by natural
products seems to act against endothelial dysfunction by reestablishing the
vascular function and elevating nitric oxide levels (by increasing the amounts of
substrate (L-arginine, and endothelial nitric oxide synthase activation and
stabilisation) as well as decreasing the generation of reactive species (formed
by uncoupledendothelial nitric oxide synthase). This review summarises several
topics regarding arginase inhibition by natural substances as well as indicating
this pathway as an emergent strategy to elevate nitric oxide levels in disorders
involving endothelial dysfunction. In addition, some aspects regarding structural
activity and future perspectives are discussed.
PMID- 29342481
TI - [Pioneering research developments in psychiatry].
PMID- 29342482
TI - [Driving ability with neurological diseases].
PMID- 29342483
TI - [Fitness to drive after stroke].
AB - In Germany, patient information and expert testimony on driving ability requires
knowledge of the corresponding legislation and the Guideline for expertises on
driver aptitude. The testimony should clearly identify handicaps with regard to
driving, give estimates on the future risks of a sudden loss of control, and also
consider personal attitudes such as inadequate behavior, lack of insight etc.
Physical handicaps often can be compensated for by restrains or restrictions such
as vehicle modifications, daylight driving only etc.Both, information and
testimony must give estimates on the risks of a sudden loss of control while
driving by stroke recurrence or epileptic seizures. In accordance with the Risk
of-Harm-Formula of the Canadian Cardiovascular Society methods are being
discussed, by which an estimate of harmful traffic accidents due to stroke
recurrence can be calculated.
PMID- 29342484
TI - [(Neuro-)ophthalmogical aspects of driving ability].
AB - The requirements regarding visual functioning needed for driving ability are
stipulated in Annex 6 of the German driving licence regulations: In case of a
visual disorder an ophthalmological assessment is essential: It is of crucial
importance for the examining ophthalmologist to exhaust all ocular-medical
possibilities to enable the applicant to maintain or regain his driving
permission. In the overwhelming majority of the cases this is eminently
feasible.However, there is no way to attest driving ability in a patient
suffering acute one-sided visual loss for a period of 3 months on the basis of
legal recommendations. Concerning oculomotor disturbances, the expansion of the
diplopic central visual field and the subjective restriction caused thereby are
important: the central 20 degree area must be free of diplopia.According to the
German driving license regulations, absolute homonymous visual field defects such
as hemianopsia or quadrantic defects affecting the visual centre are incompatible
with driving an automobile. Even training measures causing the patient to
experience a sense of smooth orientation do nothing to mitigate this fact.Dealing
with serious disturbances of visual function, as a matter of principle an
ophthalmologist should provide an additional expertise before a positive decision
on driving ability is made.
PMID- 29342485
TI - [Driving ability in mild cognitive impairment and dementia].
AB - Executive functions, visuo-spatial processing and control of behaviour are
pertinent for safe driving. In patients with mild cognitive impairment and
dementia, these abilities can be impaired, in addition to age-related
impairments, and driving ability can be compromised at an early stage.
Neurologists and psychiatrists play an important role in the examination,
counseling and, if required, the issuing of a medical driving ban. Mistakes in
this process may ensue forensic sequelae for the involved physicians. The present
article presents the relevant conditions and associated cognitive impairments,
and gives some recommendations on the neuropsychological workup and on the
communication with patients and relatives concerning driving.
PMID- 29342486
TI - ?
PMID- 29342487
TI - [Application of Intrabronchial Valves in High Risk Patients with Bronchopleural
Fistula: an Alternative Therapeutic Option].
AB - OBJECTIVES: Persistent air leak or bronchopleural fistula (BPF) is a challenging
and frequently observed problem after pulmonary resection and may lead to
prolonged chest tube therapy. One efficient nonsurgical approach to manage such a
fistula is the application of intrabronchial valves. This may support earlier
chest tube removal and hospital discharge. METHODS: Between 04/2015 and 03/2017,
n = 8 patients (n = 4 female) with severe pleural empyema and necrotising lung
tissue defects developed prolonged air leak and persistent BPF after surgery.
Radiological and bronchoscopical investigations revealed the presence of a BPF.
For closure, intrabronchial valves were endoscopically inserted into the affected
bronchi. In patients with repeat development of empyema, a chest wall window was
required (n = 6 patients). RESULTS: The mean age was 61 years (45 - 85 years).
After repeated surgical debridement, the space was sterile and the chest wall
window was closed. After valve placement, air leaks were no longer detectable. In
all patients, the procedures were well tolerated without any negative events.
After successful valve placement, chest tubes could be removed in all n = 8
patients within 7 days (3 - 15 days) and patients were discharged thereafter.
CONCLUSIONS: Placement of intrabronchial valves presents an alternative option to
conventional surgical and non-surgical methods for the treatment of postoperative
persistent air leak or BPF. Particularly in high risk patients, this procedure is
safe and effective.
PMID- 29342488
TI - The Effects of Folate Supplementation on Diabetes Biomarkers Among Patients with
Metabolic Diseases: A Systematic Review and Meta-Analysis of Randomized
Controlled Trials.
AB - Although several studies have evaluated the effect of folate supplementation on
diabetes biomarkers among patients with metabolic diseases, findings are
inconsistent. This review of randomized controlled trials (RCTs) was performed to
summarize the evidence on the effects of folate supplementation on diabetes
biomarkers among patients with metabolic diseases. Randomized-controlled trials
(RCTs) published in PubMed, EMBASE, Web of Science and Cochrane Library databases
up to 1 September 2017 were searched. Two review authors independently assessed
study eligibility, extracted data, and evaluated risk of bias of included
studies. Heterogeneity was measured with a Q-test and with I2 statistics. Data
were pooled by using the fix or random-effect model based on the heterogeneity
test results and expressed as standardized mean difference (SMD) with 95%
confidence interval (CI). A total of sixteen randomized controlled trials
involving 763 participants were included in the final analysis. The current meta
analysis showed folate supplementation among patients with metabolic diseases
significantly decreased insulin (SMD -1.28; 95% CI, -1.99, -0.56) and homeostasis
model assessment of insulin resistance (HOMA-IR) (SMD -1.28; 95% CI, -1.99,
0.56). However, folate supplementation did not affect fasting plasma glucose
(FPG) (SMD -0.30; 95% CI, -0.63, 0.02) and hemoglobin A1C (HbA1c) (SMD -0.29; 95%
CI, -0.61, 0.03). The results of this meta-analysis study demonstrated that
folate supplementation may result in significant decreases in insulin levels and
HOMA-IR score, but does not affect FPG and HbA1c levels among patients with
metabolic diseases.
PMID- 29342489
TI - Correction: Artificial intelligence may help in predicting the need for
additional surgery after endoscopic resection of T1 colorectal cancer.
PMID- 29342490
TI - Detection of early neoplasia in Barrett's esophagus using lectin-based near
infrared imaging: an ex vivo study on human tissue.
AB - BACKGROUND AND STUDY AIMS: Endoscopic surveillance for Barrett's esophagus (BE)
is limited by long procedure times and sampling error. Near-infrared (NIR)
fluorescence imaging minimizes tissue autofluorescence and optical scattering. We
assessed the feasibility of a topically applied NIR dye-labeled lectin for the
detection of early neoplasia in BE in an ex vivo setting. METHODS: Consecutive
patients undergoing endoscopic mucosal resection (EMR) for BE-related early
neoplasia were recruited. Freshly collected EMR specimens were sprayed at the
bedside with fluorescent lectin and then imaged. Punch biopsies were collected
from each EMR under NIR light guidance. We compared the fluorescence intensity
from dysplastic and nondysplastic areas within EMRs and from punch biopsies with
different histological grades. RESULTS: 29 EMR specimens were included from 17
patients. A significantly lower fluorescence was found for dysplastic regions
across whole EMR specimens (P < 0.001). We found a 41 % reduction in the
fluorescence of dysplastic compared to nondysplastic punch biopsies (P < 0.001),
with a sensitivity and specificity for dysplasia detection of 80 % and 82.9 %,
respectively. CONCLUSION: Lectin-based NIR imaging can differentiate dysplastic
from nondysplastic Barrett's mucosa ex vivo.
PMID- 29342491
TI - Covered vs. uncovered self-expandable metal stents for malignant distal biliary
strictures: a systematic review and meta-analysis.
AB - BACKGROUND: Self-expandable metal stents (SEMS) are used for palliation of distal
malignant biliary strictures, but the role of covered SEMS is less clear. We
performed an up-to-date meta-analysis to compare the performance of covered and
uncovered SEMS in patients with unresectable distal malignant biliary strictures.
METHODS: A computerized medical search was performed using MEDLINE, EMBASE, and
the Cochrane Library between 2000 and December 2016 to identify all randomized
trials that compared covered with uncovered SEMS in patients with distal
malignant biliary strictures. Primary outcomes were stent failure and patient
mortality; secondary outcomes were stent dysfunction and adverse events. Pooled
estimates were computed using the random effects model. RESULTS: Overall, 11 RCTs
involving 1272 patients were included. The primary outcomes of stent failure and
patient mortality did not differ significantly between covered and uncovered SEMS
(hazard ratio [HR] 0.68, 95 % confidence interval [CI] 0.40 - 1.17; HR 0.89, 95
%CI 0.76 - 1.05, respectively). However, stent migration and sludge formation
were much more common with covered SEMS (odds ratio [OR] 5.11, 95 %CI 1.84 -
14.17; OR 2.46, 95 %CI 1.37 - 4.43). The use of covered SEMS was associated with
a lower rate of tumor ingrowth (OR 0.21, 95 %CI 0.09 - 0.50) but a higher rate of
tumor overgrowth (OR 2.00, 95 %CI 1.15 - 3.48) compared with uncovered stents.
The rates of procedure-related adverse events were similar in both groups.
CONCLUSION: There was a risk reduction of about 32 % for both stent failure and
patient mortality with covered SEMS but this difference was not significant.
Migration and sludge rates were higher with covered SEMS, whereas tumor ingrowth
was more likely with uncovered SEMS. The data show no added benefit of covered
SEMS; further stent evolution is desirable.
PMID- 29342492
TI - Efficacy and safety of endoscopic radiofrequency ablation for unresectable
extrahepatic cholangiocarcinoma: a randomized trial.
AB - BACKGROUND: Endoscopic placement of biliary stents to relieve jaundice is the
main palliative treatment for unresectable extrahepatic cholangiocarcinoma.
Endoscopic biliary radiofrequency ablation (RFA) has been reported to prolong
stent patency, which may be beneficial in improving patient survival. However,
available evidence is still insufficient, as most reported studies are
retrospective case series. The aim of this study was to explore the clinical
effect and safety of RFA in patients with unresectable extrahepatic
cholangiocarcinoma. METHODS: 65 patients with unresectable extrahepatic
cholangiocarcinoma, except Bismuth type III and IV hilar cholangiocarcinoma, were
enrolled and randomly underwent either RFA combined with biliary stenting (RFA +
stent group; n = 32) or biliary stent only (stent-only group; n = 33). Overall
survival time, stent patency period, and postoperative adverse events were
recorded. RESULTS: In the 21-month follow-up period, the overall mean survival
time was significantly longer in the RFA + stent group than in the stent-only
group (13.2 +/- 0.6 vs. 8.3 +/- 0.5 months; P < 0.001). The mean stent patency
period of the RFA + stent group was also significantly longer than that of the
stent-only group (6.8 vs. 3.4 months; P = 0.02). There was no significant
difference in the incidence of postoperative adverse events between the two
groups (6.3 % [2/32] vs. 9.1 % [3/33]; P = 0.67). CONCLUSION: Endoscopic RFA
combined with stenting can significantly prolong survival and the stent patency
period without increasing the incidence of adverse events in patients with
extrahepatic cholangiocarcinoma patient, except Bismuth type III and IV hilar
cholangiocarcinoma. This approach can be considered as a safe and effective
palliative treatment for these patients.
PMID- 29342493
TI - Molecular Docking Studies on Isocytosine Analogues as Xanthine Oxidase
Inhibitors.
AB - Flexible docking simulations were carried out on a series of isocytosine analogs
as xanthine oxidase (XO) inhibitors. This was done by analysing the interaction
of these compounds at the active site of XO. The binding free energies of the
analogs were calculated using GoldScore. The binding modes of the best-fit
conformation were studied, providing some handy important interactions. The
results obtained henceforth provided an insight into the pharmacophoric
structural requirements for XO inhibition for this class of molecules.
PMID- 29342494
TI - How Does the Patient React After Reading the Informed Consent Form of a
Gynecological Surgery? A Qualitative Study.
AB - OBJECTIVE: To analyze the reaction of women after reading the Informed Consent
Form (ICF) before undergoing elective gynecological/urogynecological surgeries.
METHODS: A qualitative study with 53 women was conducted between September 2014
and May 2015. The analysis of the content was conducted after a scripted
interview was made in a reserved room and transcribed verbatim. We read the ICF
once more in front of the patient, and then she was interviewed according to a
script of questions about emotions and reactions that occurred about the
procedure and her expectations about the intra- and postoperative period.
RESULTS: The women had a mean age of 52 years, they were multiparous, and most
had only a few years of schooling (54.7%). The majority (60.4%) of them had
undergone urogynecological surgeries. Hysterectomy and colpoperineoplasty were
the most frequent procedures. Ten women had not undergone any previous abdominal
surgery. Fear (34.6%) was the feeling that emerged most frequently from the
interviews after reading the ICF, followed by indifference (30.8%) and
resignation (13.5%). Nine women considered their reaction unexpected after
reading the ICF. Three patients did not consider the information contained in the
ICF to be sufficient, and 3 had questions about the surgery after reading the
document. CONCLUSION: Reading the ICF generates fear in most women; however,
they believe this feeling did not interfere in their decision-making process.
PMID- 29342495
TI - Improving Perinatology Residents' Skills in Breaking Bad News: A Randomized
Intervention Study.
AB - OBJECTIVE: Breaking bad news (BBN) is particularly difficult in perinatology.
Previous research has shown that BBN skills can be learned and improved when
taught and practiced. This project evaluated whether a structured training
session would enhance perinatology residents' skills in BBN. METHODS: This was a
randomized controlled intervention study with year 1 to 4 Perinatology residents
from a medical school in Brazil, during the 2014/15 school year. A total of 61
out of 100 (61%) eligible residents volunteered to a structured training program
involving communicating a perinatal loss to a simulated patient (SP) portraying
the mother followed by the SP's immediate feedback, both video recorded. Later,
residents were randomly assigned to BBN training based on a setting, perception,
invitation, knowledge, emotion and summary (SPIKES) strategy with video reviews
(intervention) or no training (control group). All residents returned for a
second simulation with the same SP blinded to the intervention and portraying a
similar case. Residents' performances were then evaluated by the SP with a
checklist. The statistical analysis included a repeated measures analysis of
covariance (RM-ANCOVA). Complementarily, the residents provided their perceptions
about the simulation with feedback activities. RESULTS: Fifty-eight residents
completed the program. The simulations lasted on average 12 minutes, feedback 5
minutes and SPIKES training between 1h and 2h30m. There was no significant
difference in the residents' performances according to the SPs' evaluations (p =
0.55). The participants rated the simulation with feedback exercises highly.
These educational activities might have offset SPIKES training impact.
CONCLUSION: The SPIKES training did not significantly impact the residents'
performance. The residents endorsed the simulation with feedback as a useful
training modality. Further research is needed to determine which modality is more
effective.
PMID- 29342496
TI - Adverse Events in the Treatment of Periprosthetic Fractures Around the Knee - a
Clinical and Radiological Outcome Analysis.
AB - BACKGROUND: The incidence of periprosthetic fractures associated with total knee
arthroplasty (PpFxK) has been reported to be 0.3 - 5.5%. 40% of all cases are
related to revision TKA. The most common localisation is the distal femur.
Classification is performed according to Rorabeck (RB). RB I - II fractures are
usually treated with locked plating and retrograde intramedullary nailing,
whereas RB III fractures are an indication for revision arthroplasty using a
hinged endoprosthesis. PpFxK of the patella can be classified according to
Goldberg and PpFxK of the proximal tibia can be grouped as in Felix.
Interprosthetic fractures can be regarded as a special type of PpFx. Due to the
increasing numbers of TKA being performed, increasing numbers of adverse events
in arthroplasty can be expected. Adverse events in the treatment of PpFxK occur
in up to 41% of patients according to the literature and revision is needed in
approximately 29% of all cases. Risk factors are age, osteoporosis, infection,
malalignment, osteolysis/loosening of the implant and status post revision.
PATIENTS: A clinical and radiographic follow-up was performed with 50 patients
(14 men, 36 women) treated for PpFxK of the femur, tibia and patella between 2011
and 2015 at the department of arthroplasty at a level 1 trauma center in Europe.
RESULTS: The follow-up of all patients was 68%, with an average of 19.1 +/- 14.6
(1 - 49) months between PpFxK and clinical follow-up. 16% of the patients were
allocated for further treatment or revision surgery from other hospitals. The
patients' median age was 78.0 +/- 8.8 (55 - 94) years. Most patients were
affected by several orthopaedic and internal medical comorbidities. PpFxK
classified as RB II were the most common fractures (60%, n = 30). PpFxK usually
occurred 5.0 +/- 4.8 (0 - 20) years after index TKA (primary or revision TKA),
mostly in patients with CR-retaining endoprosthesis, whereas PpFxK according to
Felix occurred significantly earlier and mostly in hinged TKAs. Patients achieved
on average a mean Oxford Knee Score of 31.1 +/- 9.9 (14 - 46) points. The
functional Knee Society Score (KSS) was 52.6 +/- 24.4 (20 - 100) and the mean KSS
was 58.7 +/- 26.8 (0 - 99) points (n = 25). Radiographic evaluation of the RB I -
II patients showed frontal and sagittal malalignment in 20.6% of all cases after
reduction and plate fixation. The overall rate of surgical adverse events was
50%; 44% of all RB patients needed revision surgery. Adverse events comprised non
union, failure of osteosynthesis, infection, wound healing disorders and re
fractures in the RB II and the Felix subgroup. CONCLUSION: PpFxK are severe
injuries and are associated with a high rate of adverse events related to
treatment. Patients often have a complex background and a history of revision
surgery or periprosthetic joint infection. The treatment of PpFxK should
therefore take place at a centre with expertise in traumatology as well as in
revision arthroplasty. Preoperative infection diagnostic testing as well as
adequate imaging (X-rays and CT) are essential. We furthermore advise early
evaluation of revision arthroplasty, especially in elderly patients suffering
from PpFxK with insufficient bone quality around the TKA and closeness between
fracture and TKA. In the case of plate fixation, it is important to give
attention to correct reduction - to prevent non-union, loosening of the implant
and failure of the osteosynthesis - as well as to consider double plating.
PMID- 29342497
TI - Non-antipsychotic catecholaminergic drugs for antipsychotic-induced tardive
dyskinesia.
AB - BACKGROUND: Tardive dyskinesia (TD) is a disabling movement disorder associated
with the prolonged use of antipsychotic medication. Several strategies have been
examined in the treatment of TD. Currently, however, there is no clear evidence
of the effectiveness of these drugs in TD and they have been associated with many
side effects. One particular strategy would be to use pharmaceutical agents which
are known to influence the catecholaminergic system at various junctures.
OBJECTIVES: 1. To determine the effects of any of the following drugs for
antipsychotic-induced TD in people with schizophrenia or other chronic mental
illnesses.i. Drugs which influence the noradrenergic system.ii. Dopamine receptor
agonists.iii. Dopamine receptor antagonists.iv. Dopamine-depletor drugs.v. Drugs
that increase the production or release of dopamine.2. To examine whether any
improvement occurred with short periods of intervention (less than 6 weeks) and,
if this did occur, whether this effect was maintained at longer periods of follow
up.3. To examine if there was a differential effect for the various compounds.4.
To examine whether the use of non-antipsychotic catecholaminergic drugs are most
effective in those with more recent onset TD (less than five years). SEARCH
METHODS: We retrieved 712 references from searching the Cochrane Schizophrenia
Group Trials Register (July 2015 and April 2017). We also inspected references of
all identified studies for further trials and contacted authors of trials for
additional information. SELECTION CRITERIA: We selected studies if they were
randomised controlled trials focusing on people with schizophrenia or other
chronic mental illnesses and antipsychotic-induced tardive dyskinesia. We
compared the use of catecholaminergic interventions versus placebo, no
intervention, or any other intervention for the treatment of antipsychotic
induced tardive dyskinesia. DATA COLLECTION AND ANALYSIS: We independently
extracted data from these trials and we estimated risk ratios (RRs) with 95%
confidence intervals (CIs). We assumed that people who left the studies early had
no improvement. MAIN RESULTS: There are 10 included trials (N = 261) published
between 1973 and 2010; eight are new from the 2015 and 2017 update searches.
Forty-eight studies are excluded. Participants were mostly chronically mentally
ill inpatients in their 50s, and studies were primarily of short (2 to 6 weeks)
duration. The overall risk of bias in these studies was unclear, mainly due to
poor reporting of allocation concealment and generation of the sequence. Studies
were also not clearly blinded and we are unsure if data are incomplete or
selectively reported, or if other biases were operating.One small, three-arm
trial found that both alpha-methyldopa (N = 20; RR 0.33, 95% CI 0.14 to 0.80; low
quality evidence) and reserpine (N = 20; RR 0.52 95% CI 0.29 to 0.96; low-quality
evidence) may lead to a clinically important improvement in tardive dyskinesia
symptoms compared with placebo after 2 weeks' treatment, but found no evidence of
a difference between alpha-methyldopa and reserpine (N = 20; RR 0.60, 95% CI 0.19
to 1.86; very low quality evidence). Another small trial compared tetrabenazine
and haloperidol after 18 weeks' treatment and found no evidence of a difference
on clinically important improvement in tardive dyskinesia symptoms (N = 13; RR
0.93, 95% CI 0.45 to 1.95; very low quality evidence). No study reported on
adverse events.For remaining outcomes there was no evidence of a difference
between any of the interventions: alpha-methyldopa versus placebo for
deterioration of tardive dyskinesia symptoms (1 RCT; N = 20; RR 0.33, 95% CI 0.02
to 7.32; very low quality evidence), celiprolol versus placebo for leaving the
study early (1 RCT; N = 35; RR 5.28, 95% CI 0.27 to 102.58; very low quality
evidence) and quality of life (1 RCT; N = 35; RR 0.87, 95% CI 0.68 to 1.12; very
low quality evidence), alpha-methyldopa versus reserpine for deterioration of
tardive dyskinesia symptoms (1 RCT; N = 20; not estimable, no reported events;
very low quality evidence), reserpine or carbidopa/levodopa versus placebo for
deterioration of tardive dyskinesia symptoms (2 RCTs; N = 37; RR 1.18, 95% CI
0.35 to 3.99; very low quality evidence), oxypertine versus placebo for
deterioration of mental state (1 RCT; N = 42; RR 2.20, 95% CI 0.22 to 22.45; very
low quality evidence), dopaminergic drugs (amantadine, bromocriptine, tiapride,
oxypertine, carbidopa/levodopa) versus placebo for leaving the study early (6
RCTs; N = 163; RR 1.29, 95% CI 0.65 to 2.54; very low quality evidence), and
tetrabenazine versus haloperidol for deterioration of tardive dyskinesia symptoms
(1 RCT; N = 13; RR 1.17, 95% CI 0.09 to 14.92) and leaving the study early (1
RCT; N = 13; RR 0.23, 95% CI 0.01 to 4.00). AUTHORS' CONCLUSIONS: Although there
has been a large amount of research in this area, many studies were excluded due
to inherent problems in the nature of their cross-over designs. Usually data are
not reported before the cross-over and the nature of TD and its likely response
to treatments make it imprudent to use this data. The review provides little
usable information for service users or providers and more well-designed and well
reported studies are indicated.
PMID- 29342498
TI - Patient reminder and recall interventions to improve immunization rates.
AB - BACKGROUND: Immunization rates for children and adults are rising, but coverage
levels have not reached optimal goals. As a result, vaccine-preventable diseases
still occur. In an era of increasing complexity of immunization schedules, rising
expectations about the performance of primary care, and large demands on primary
care providers, it is important to understand and promote interventions that work
in primary care settings to increase immunization coverage. One common theme
across immunization programs in many nations involves the challenge of
implementing a population-based approach and identifying all eligible recipients,
for example the children who should receive the measles vaccine. However, this
issue is gradually being addressed through the availability of immunization
registries and electronic health records. A second common theme is identifying
the best strategies to promote high vaccination rates. Three types of strategies
have been studied: (1) patient-oriented interventions, such as patient reminder
or recall, (2) provider interventions, and (3) system interventions, such as
school laws. One of the most prominent intervention strategies, and perhaps best
studied, involves patient reminder or recall systems. This is an update of a
previously published review. OBJECTIVES: To evaluate and compare the
effectiveness of various types of patient reminder and recall interventions to
improve receipt of immunizations. SEARCH METHODS: We searched CENTRAL, MEDLINE,
Embase and CINAHL to January 2017. We also searched grey literature and trial
registers to January 2017. SELECTION CRITERIA: We included randomized trials,
controlled before and after studies, and interrupted time series evaluating
immunization-focused patient reminder or recall interventions in children,
adolescents, and adults who receive immunizations in any setting. We included no
intervention control groups, standard practice activities that did not include
immunization patient reminder or recall, media-based activities aimed at
promoting immunizations, or simple practice-based awareness campaigns. We
included receipt of any immunizations as eligible outcome measures, excluding
special travel immunizations. We excluded patients who were hospitalized for the
duration of the study period. DATA COLLECTION AND ANALYSIS: We used the standard
methodological procedures expected by Cochrane and the Cochrane Effective
Practice and Organisation of Care (EPOC) Group. We present results for individual
studies as relative rates using risk ratios, and risk differences for randomized
trials, and as absolute changes in percentage points for controlled before-after
studies. We present pooled results for randomized trials using the random-effects
model. MAIN RESULTS: The 75 included studies involved child, adolescent, and
adult participants in outpatient, community-based, primary care, and other
settings in 10 countries.Patient reminder or recall interventions, including
telephone and autodialer calls, letters, postcards, text messages, combination of
mail or telephone, or a combination of patient reminder or recall with outreach,
probably improve the proportion of participants who receive immunization (risk
ratio (RR) of 1.28, 95% confidence interval (CI) 1.23 to 1.35; risk difference of
8%) based on moderate certainty evidence from 55 studies with 138,625
participants.Three types of single-method reminders improve receipt of
immunizations based on high certainty evidence: the use of postcards (RR 1.18,
95% CI 1.08 to 1.30; eight studies; 27,734 participants), text messages (RR 1.29,
95% CI 1.15 to 1.44; six studies; 7772 participants), and autodialer (RR 1.17,
95% CI 1.03 to 1.32; five studies; 11,947 participants). Two types of single
method reminders probably improve receipt of immunizations based on moderate
certainty evidence: the use of telephone calls (RR 1.75, 95% CI 1.20 to 2.54;
seven studies; 9120 participants) and letters to patients (RR 1.29, 95% CI 1.21
to 1.38; 27 studies; 81,100 participants).Based on high certainty evidence,
reminders improve receipt of immunizations for childhood (RR 1.22, 95% CI 1.15 to
1.29; risk difference of 8%; 23 studies; 31,099 participants) and adolescent
vaccinations (RR 1.29, 95% CI 1.17 to 1.42; risk difference of 7%; 10 studies;
30,868 participants). Reminders probably improve receipt of vaccinations for
childhood influenza (RR 1.51, 95% CI 1.14 to 1.99; risk difference of 22%; five
studies; 9265 participants) and adult influenza (RR 1.29, 95% CI 1.17 to 1.43;
risk difference of 9%; 15 studies; 59,328 participants) based on moderate
certainty evidence. They may improve receipt of vaccinations for adult
pneumococcus, tetanus, hepatitis B, and other non-influenza vaccinations based on
low certainty evidence although the confidence interval includes no effect of
these interventions (RR 2.08, 95% CI 0.91 to 4.78; four studies; 8065
participants). AUTHORS' CONCLUSIONS: Patient reminder and recall systems, in
primary care settings, are likely to be effective at improving the proportion of
the target population who receive immunizations.
PMID- 29342500
TI - Does Rheumatoid Arthritis Cause an Obesity Paradox? Comment on the Article by
Sparks et al.
PMID- 29342501
TI - Selective Activation of Tumor Necrosis Factor Receptor II Induces
Antiinflammatory Responses and Alleviates Experimental Arthritis.
AB - OBJECTIVE: Treg cells modulate immune responses and can suppress the development
of autoimmune diseases. Tumor necrosis factor receptor II (TNFRII) has been
recognized as a key receptor on these cells that facilitates expansion and
stabilization of CD4+ Treg cells. The purpose of the present study was to
investigate the therapeutic activity of a novel TNFRII agonist in experimental
arthritis as well as the role of different Treg cell subsets. METHODS: A novel
mouse TNFRII-selective fusion protein (EHD2-sc-mTNFR2 ) was generated by genetic
engineering. Mouse T cells were incubated together with interleukin-2 and/or EHD2
sc-mTNFR2 , and the effects on Treg cells were analyzed by flow cytometry. Mice
with collagen-induced arthritis (CIA) were treated with EHD2-sc-mTNFR2 or saline,
and the therapeutic effects were monitored and characterized. RESULTS: Selective
activation of TNFRII was found to expand both CD4+ and CD8+ Treg cells. Moreover,
TNFRII activation elevated the number of CD4+CD25+ and CD8+CD25+ Treg cells and
increased the number of FoxP3-expressing cells in CD8+, but not CD4+, Treg cells,
indicating different mechanisms of TNFRII-induced expansion of diverse T cell
subsets with suppressive activity. In the CIA model, we demonstrated that
administration of the TNFRII agonist EHD2-sc-mTNFR2 led to the expansion of both
CD4+ and CD8+ Treg cells in vivo and induced antiinflammatory responses that
alleviated arthritis. CONCLUSION: Our findings support the use of TNFRII
selective therapeutics as an effective approach to the treatment of arthritic
disease and possibly other inflammatory and autoimmune diseases.
PMID- 29342499
TI - Efficacy and Safety of Cyclophosphamide Treatment in Severe Juvenile
Dermatomyositis Shown by Marginal Structural Modeling.
AB - OBJECTIVE: In patients with severe or refractory juvenile dermatomyositis (DM),
second-line treatments may be required. Cyclophosphamide (CYC) is used to treat
some connective tissue diseases, but evidence of its efficacy in juvenile DM is
limited. This study was undertaken to describe clinical improvement in juvenile
DM patients treated with CYC and model the efficacy of CYC treatment compared to
no CYC treatment. METHODS: Clinical data on skin, global, and muscle disease for
patients recruited to the Juvenile DM Cohort and Biomarker Study were analyzed.
Clinical improvement following CYC treatment was described using unadjusted
analysis. Marginal structural models (MSMs) were used to model treatment efficacy
and adjust for confounding by indication. RESULTS: Compared to the start of CYC
treatment, there were reductions at 6, 12, and 24 months in skin disease (P = 1.3
* 10-10 ), global disease (P = 2.4 * 10-8 ), and muscle disease (P = 8.0 * 10-10
) for 56 patients treated with CYC in unadjusted analysis. Limited evidence
suggested a reduction in glucocorticoid dose (P = 0.047) in patients treated with
CYC. MSM analysis showed reduced global disease and skin disease in patients who
started an ~6-month course of CYC treatment >12 months ago compared to patients
never or not yet treated with CYC. In the treated patients, the modified skin
Disease Activity Score for juvenile DM was 1.19 units lower (P = 0.0085) and the
physician's global assessment was 0.66 units lower (P = 0.027). Minor adverse
events were reported in 3 patients within 1 year of stopping CYC. CONCLUSION: Our
findings indicate that CYC is efficacious with no short-term side effects.
Improvements in skin, global, and muscle disease were observed. Further studies
are required to evaluate longer-term side effects.
PMID- 29342502
TI - Antiphospholipid Antibodies Inhibit Trophoblast Toll-Like Receptor and
Inflammasome Negative Regulators.
AB - OBJECTIVE: Women with antiphospholipid antibodies (aPL) are at risk for pregnancy
complications associated with poor placentation and placental inflammation.
Although these antibodies are heterogeneous, some anti-beta2 -glycoprotein I
(anti-beta2 GPI) antibodies can activate Toll-like receptor 4 (TLR-4) and NLRP3
in human first-trimester trophoblasts. The objective of this study was to
determine the role of negative regulators of TLR and inflammasome function in aPL
induced trophoblast inflammation. METHODS: Human trophoblasts were not treated or
were treated with anti-beta2 GPI aPL or control IgG in the presence or absence of
the common TAM (TYRO3, AXL, and Mer tyrosine kinase [MERTK]) receptor ligand
growth arrest-specific protein 6 (GAS6) or the autophagy-inducer rapamycin. The
expression and function of the TAM receptor pathway and autophagy were measured
by quantitative reverse transcription-polymerase chain reaction (qRT-PCR),
Western blotting, and enzyme-linked immunosorbent assay (ELISA). Antiphospholipid
antibody-induced trophoblast inflammation was measured by qRT-PCR, activity
assays, and ELISA. RESULTS: Anti-beta2 GPI aPL inhibited trophoblast TAM receptor
function by reducing cellular expression of the receptor tyrosine kinases AXL and
MERTK and the ligand GAS6. The addition of GAS6 blocked the effects of aPL on the
TLR-4-mediated interleukin-8 (IL-8) response. However, the NLRP3 inflammasome
mediated IL-1beta response was not affected by GAS6, suggesting that another
regulatory pathway was involved. Indeed, anti-beta2 GPI aPL inhibited basal
trophoblast autophagy, and reversing this with rapamycin inhibited aPL-induced
inflammasome function and IL-1beta secretion. CONCLUSION: Basal TAM receptor
function and autophagy may serve to inhibit trophoblast TLR and inflammasome
function, respectively. Impairment of TAM receptor signaling and autophagy by
anti-beta2 GPI aPL may allow subsequent TLR and inflammasome activity, leading to
a robust inflammatory response.
PMID- 29342503
TI - Molecular Basis for Dysregulated Activation of NKX2-5 in the Vascular Remodeling
of Systemic Sclerosis.
AB - OBJECTIVE: NKX2-5 is a homeobox transcription factor that is required for the
formation of the heart and vessels during development, with significant postnatal
down-regulation and reactivation in disease states, characterized by vascular
remodeling. The purpose of this study was to investigate mechanisms that activate
NKX2-5 expression in diseased vessels, such as systemic sclerosis (scleroderma;
SSc)-associated pulmonary hypertension (PH), and to identify genetic variability
that potentially underlies susceptibility to specific vascular complications.
METHODS: We explored NKX2-5 expression in biopsy samples from patients with SSc
associated PH and in pulmonary artery smooth muscle cells (PASMCs) from patients
with scleroderma. Disease-associated putative functional single-nucleotide
polymorphisms (SNPs) at the NKX2-5 locus were cloned and studied in reporter gene
assays. SNP function was further examined through protein-DNA binding assays,
chromatin immunoprecipitation assays, and RNA silencing analyses. RESULTS:
Increased NKX2-5 expression in biopsy samples from patients with SSc-associated
PH was localized to remodeled vessels and PASMCs. Meta-analysis of 2 independent
scleroderma cohorts revealed an association of rs3131917 with scleroderma (P =
0.029). We demonstrated that disease-associated SNPs are located in a novel
functional enhancer, which increases NKX2-5 transcriptional activity through the
binding of GATA-6, c-Jun, and myocyte-specific enhancer factor 2C. We also
characterized an activator/coactivator transcription-enhancer factor domain 1
(TEAD1)/Yes-associated protein 1 (YAP1) complex, which was bound at rs3095870,
another functional SNP, with TEAD1 binding the risk allele and activating the
transcription of NKX2-5. CONCLUSION: NKX2-5 is genetically associated with
scleroderma, pulmonary hypertension, and fibrosis. Functional evidence revealed a
regulatory mechanism that results in NKX2-5 transcriptional activation in PASMCs
through the interaction of an upstream promoter and a novel downstream enhancer.
This mechanism can act as a model for NKX2-5 activation in cardiovascular disease
characterized by vascular remodeling.
PMID- 29342504
TI - Polyarthralgias and Papulonodules in a 56-Year-Old Woman.
PMID- 29342505
TI - Reply.
PMID- 29342506
TI - Effects of a Dietary Approach to Stop Hypertension (DASH) Diet Intervention on
Serum Uric Acid in African Americans With Hypertension.
AB - OBJECTIVE: To examine whether partial replacement of a diet typical of the
average American diet with Dietary Approaches to Stop Hypertension (DASH)-related
foods in the home environment lowers the serum uric acid (UA) level in
individuals with hypertension. METHODS: We conducted an ancillary study of a
randomized trial of African American adults with controlled hypertension from an
urban clinic. Participants were assigned to either a control group or an
intervention (DASH-Plus) group. DASH-Plus participants received coach-directed
dietary advice, assistance with purchasing DASH-related foods ($30/week), and
home delivery of food via a community supermarket. Participants in the control
group received a DASH diet brochure and a debit card account ($30/week) to
purchase foods. Serum UA levels were measured at baseline and after 8 weeks.
RESULTS: Of the original 123 randomized participants, 117 had available serum UA
measurements. Seventy percent of the participants were women, the mean +/- SD age
was 59 +/- 9.5 years, and the mean +/- SD serum UA level was 6.4 +/- 1.7 mg/dl.
The DASH-Plus diet did not reduce serum UA levels compared with the control diet
(difference in difference -0.01 mg/dl [95% confidence interval -0.39, 0.38]).
However, there was a significant trend toward a greater reduction in the serum UA
level in participants with higher baseline serum UA levels (P for trend = 0.008).
Baseline changes in the serum UA level were inversely associated with changes in
systolic blood pressure (P = 0.002), diastolic blood pressure (P = 0.001), and
urinary sodium excretion (P = 0.05). CONCLUSION: Overall, in African American
individuals, partial replacement of a typical diet with DASH foods did not lower
serum UA levels compared with a control diet. However, there was a significant
trend toward a greater reduction in serum UA levels in subjects with higher
baseline serum UA levels. Furthermore, changes in serum UA levels were associated
with known correlates, suggesting heterogeneity of effects in the treatment and
control arms. Future pragmatic studies of consumption of the DASH diet to lower
serum UA levels should optimize replacement strategies and enroll individuals
with hyperuricemia or gout.
PMID- 29342508
TI - Features, Treatment, and Outcomes of Macrophage Activation Syndrome in Childhood
Onset Systemic Lupus Erythematosus.
AB - OBJECTIVE: To describe the features and treatment of macrophage activation
syndrome (MAS) in a single-center cohort of patients with childhood-onset
systemic lupus erythematosus (SLE), and to compare childhood-onset SLE
manifestations and outcomes between those with and those without MAS. METHODS: We
included all patients with childhood-onset SLE followed up at The Hospital for
Sick Children from 2002 to 2012, and identified those also diagnosed as having
MAS. Demographic, clinical, and laboratory features of MAS and SLE, medication
use, hospital and pediatric intensive care unit (PICU) admissions, as well as
damage indices and mortality data were extracted from the Lupus database.
Student's t-tests and Fisher's exact tests were used to compare continuous and
categorical variables, respectively. We calculated incidence rate ratios of
hospital and PICU admissions comparing patients with and those without MAS, using
Poisson models. Kaplan-Meier survival analysis was used to examine the time to
disease damage accrual. RESULTS: Of the 403 patients with childhood-onset SLE, 38
(9%) had MAS. The majority (68%) had concomitant MAS and SLE diagnoses. Fever was
the most common MAS clinical feature. The frequency of renal and central nervous
system disease, hospital admissions, the average daily dose of steroids, and time
to disease damage were similar between those with and those without MAS. We
observed a higher mortality rate among those with MAS (5%) than those without MAS
(0.2%) (P = 0.02). CONCLUSION: MAS was most likely to develop concomitantly with
childhood-onset SLE diagnosis. The majority of the MAS patients were successfully
treated with corticosteroids with no MAS relapses. Although the numbers were
small, there was a higher risk of death associated with MAS compared to SLE
without MAS.
PMID- 29342507
TI - The Role of Autophagy in the Degradation of Misfolded HLA-B27 Heavy Chains.
AB - OBJECTIVE: To determine whether autophagy is involved in the degradation of
misfolded HLA-B27 in experimental spondyloarthritis. METHODS: Bone marrow-derived
macrophages from HLA-B27/human beta2 -microglobulin (hbeta2 m)-transgenic rats
were incubated in the presence or absence of interferon-gamma and proteasome or
autophagy inhibitors. Immunoprecipitation, immunoblotting, and immunofluorescence
analysis were used to measure HLA-B27 heavy chains and autophagy. Autophagy was
induced using rapamycin. Macrophages from HLA-B7/hbeta2 m-transgenic and wild
type rats were used as controls. RESULTS: HLA-B27-expressing macrophages showed
phosphatidylethanolamine-conjugated microtubule-associated protein 1 light chain
3B levels similar to those in both control groups, before and after manipulation
of autophagy. Blocking autophagic flux with bafilomycin resulted in the
accumulation of misfolded HLA-B27 dimers and oligomers as well as monomers, which
was comparable with the results of blocking endoplasmic reticulum-associated
degradation (ERAD) with the proteasome inhibitor bortezomib. HLA-B7 monomers also
accumulated after blocking each degradation pathway. The ubiquitin-to-heavy chain
ratio was 2-3-fold lower for HLA-B27 than for HLA-B7. Activation of autophagy
with rapamycin rapidly eliminated ~50% of misfolded HLA-B27, while folded HLA-B27
or HLA-B7 monomeric heavy chains were minimally affected. CONCLUSION: This study
is the first to demonstrate that both autophagy and ERAD play roles in the
elimination of excess HLA class I heavy chains expressed in transgenic rats. We
observed no evidence that HLA-B27 expression modulated the autophagy pathway. Our
results suggest that impaired ubiquitination of HLA-B27 may play a role in the
accumulation of misfolded disulfide-linked dimers, the elimination of which can
be enhanced by activation of autophagy. Manipulation of the autophagy pathway
should be further investigated as a potential therapeutic target in
spondyloarthritis.
PMID- 29342509
TI - Influence of Explanatory Images on Risk Perceptions and Treatment Preference.
AB - OBJECTIVE: The aim of this study was to examine whether providing patients with a
series of balance scales (BS), depicting a reciprocal relationship between
achieving disease control and increasing the risk of infection, influences
treatment preference. METHODS: Participants were randomized to receive a
description of a medication in which risk of infection was relayed using 1 of 4
formats, including numbers only, numbers + icon array (IA), numbers + BS, or
numbers + IA + BS (i.e., combination). We compared the likelihood of starting the
medication across the 4 formats, and evaluated whether the influence of risk
formats varied by numeracy and gist risk appraisals. RESULTS: The mean +/- SE
likelihood of starting the medication was higher among participants randomized to
the combination format (3.85 +/- 0.09) compared to those who viewed the BS (3.56
+/- 0.09; P = 0.0222) or numbers-only formats (3.51 +/- 0.09; P = 0.0069).
Viewing an IA alone was associated with a lower likelihood of starting the
medication among participants lower in numeracy and endorsing a risk-avoidant
noncompensatory gist risk appraisal. Conversely, viewing an IA (with or without
the BS) was associated with a greater likelihood of starting the medication among
patients with higher numeracy and compensatory risk appraisals. CONCLUSION:
Adding explanatory images to IAs increases patient likelihood to take a
medication in those with low numeracy and a noncompensatory gist risk appraisal.
Explanatory images may be a feasible approach to improve willingness to try
medication among subjects who are especially risk averse and believe that any
risk is unacceptable.
PMID- 29342511
TI - Sign, language, and gesture in the brain: Some comments.
AB - In contrast with two widely held and contradictory views - that sign languages of
deaf people are "just gestures," or that sign languages are "just like spoken
languages" - the view from sign linguistics and developmental research in
cognition presented by Goldin-Meadow & Brentari (G-M&B) indicates a more complex
picture. We propose that neuroscience research suggests that a similar approach
needs to be taken and offer some examples from research on the brain bases of
sign language perception.
PMID- 29342512
TI - Building a single proposition from imagistic and categorical components.
AB - Bimodal bilingual language provides further evidence for the viewpoint advocated
by Goldin-Meadow & Brentari (G-M&B) that sign, speech, and gesture work together
to create a single proposition, illustrating the potential in each set of
articulators for both imagistic and categorical components. Recent advances in
formal semantics provide a framework for incorporating both imagistic and
categorical components into a single compositional system.
PMID- 29342510
TI - Validation of the Social Appearance Anxiety Scale in Patients With Systemic
Sclerosis: A Scleroderma Patient-Centered Intervention Network Cohort Study.
AB - OBJECTIVE: Systemic sclerosis (SSc) is an autoimmune disease that can cause
disfiguring changes in appearance. This study examined the structural validity,
internal consistency reliability, convergent validity, and measurement
equivalence of the Social Appearance Anxiety Scale (SAAS) across SSc disease
subtypes. METHODS: Patients enrolled in the Scleroderma Patient-centered
Intervention Network Cohort completed the SAAS and measures of appearance-related
concerns and psychological distress. Confirmatory factor analysis (CFA) was used
to examine the structural validity of the SAAS. Multiple-group CFA was used to
determine whether SAAS scores can be compared across patients with limited and
diffuse disease subtypes. Cronbach's alpha was used to examine internal
consistency reliability. Correlations of SAAS scores with measures of body image
dissatisfaction, fear of negative evaluation, social anxiety, and depression were
used to examine convergent validity. SAAS scores were hypothesized to be
positively associated with all convergent validity measures, with correlations
significant and moderate to large in size. RESULTS: A total of 938 patients with
SSc were included. CFA supported a 1-factor structure (Comparative Fit Index
0.92, Standardized Root Mean Residual 0.04, and Root Mean Square Error of
Approximation 0.08), and multiple-group CFA indicated that the scalar invariance
model best fit the data. Internal consistency reliability was good in the total
sample (alpha = 0.96) and in disease subgroups. Overall, evidence of convergent
validity was found with measures of body image dissatisfaction, fear of negative
evaluation, social anxiety, and depression. CONCLUSION: The SAAS can be reliably
and validly used to assess fear of appearance evaluation in patients with SSc,
and SAAS scores can be meaningfully compared across disease subtypes.
PMID- 29342513
TI - Is it language (yet)? The allure of the gesture-language binary.
AB - Goldin-Meadow & Brentari (G-M&B) challenge the traditional separation between
gestural and categorical language by modality, but they retain a binary
distinction. However, multiple dimensions, particularly discreteness and
combinatoriality, better carve up the range of linguistic and nonlinguistic human
communication. Investigating transformation over time along these dimensions will
reveal how the nature of language reflects human minds, rather than the world to
which language refers.
PMID- 29342514
TI - Perspectives on gesture from autism spectrum disorder: Alterations in timing and
function.
AB - The target article highlights the utility of new technology to study sign
language and gesture. Research in special populations - specifically, individuals
with autism spectrum disorder, ASD - may further illuminate sign/gesture
similarities and differences and lead to a deeper understanding of the mechanisms
of growth and change. Even verbally fluent speakers with ASD display distinctive
qualities in sign and gesture.
PMID- 29342515
TI - Emoticons in text may function like gestures in spoken or signed communication.
AB - We draw parallels between emoticons in textual communication and gesture in
signed language with respect to the interdependence of codes by describing two
contexts under which the behavior of emoticons in textual communication resembles
that of gesture in speech. Generalizing from those findings, we propose that
gesture is likely characterized by a nuanced interdependence with language
whether signed, spoken or texted.
PMID- 29342516
TI - How to distinguish gesture from sign: New technology is not the answer.
AB - Linguistic and psycholinguistic tests will be more useful than motion capture
technology in calibrating the borders between sign and gesture. The analogy
between motion capture (mocap) technology and the spectrograph is flawed because
only vocal articulators are hidden. Although information about gradience and
variability will be obtained, the technology provides less information about
linguistic constraints and categories. Better models are needed to account for
differences between co-speech and co-sign gesture (e.g., different degrees of
optionality, existence of beat gestures).
PMID- 29342517
TI - Why space is not one-dimensional: Location may be categorical and imagistic.
AB - In our commentary, we raise concerns with the idea that location should be
considered a gestural component of sign languages. We argue that psycholinguistic
studies provide evidence for location as a "categorical" element of signs. More
generally, we propose that the use of space in sign languages comes in many
flavours and may be both categorical and imagistic. In their target article,
Goldin-Meadow & Brentari (G-M&B) discuss several observations suggesting that the
use of space is imagistic and may not form part of the categorical properties of
sign languages. Specifically, they point out that (1) the number of locations
toward which agreeing verbs can be directed is not part of a discrete set, (2)
event descriptions by users of different sign languages and hearing nonsigners
exhibit marked similarities in the use of space, and (3) location as a
phonological parameter is not categorically perceived by native signers. It
should be noted that G-M&B acknowledge that categorical properties of location
and movement may simply not have been captured yet because the proper
investigative tools are not yet readily available.
PMID- 29342518
TI - Understanding gesture in sign and speech: Perspectives from theory of mind,
bilingualism, and acting.
AB - In their article, Goldin-Meadow & Brentari (G-M&B) assert that researchers must
differentiate between sign/speech and gesture. We propose that this distinction
may be useful if situated within a two-systems approach to theory of mind (ToM)
and discuss how drawing upon perspectives from bilingualism and acting can help
us understand the role of gesture in spoken/sign language.
PMID- 29342519
TI - Languages as semiotically heterogenous systems.
AB - The target article is consistent with seeing languages as semiotically
heterogenous, using categorial, depictive, and analogic semiotic signs.
"Gesture," used in the target article, is shown to be vague and not useful.
Kendon's view, criticised in the target, is restated. His proposal for
comparative semiotic analyses of how visible bodily action is used in utterance
production is reexplained.
PMID- 29342520
TI - Current and future methodologies for quantitative analysis of information
transfer in sign language and gesture data.
AB - State-of-the-art methods of analysis of video data now include motion capture and
optical flow from video recordings. These techniques allow for biological
differentiation between visual communication and noncommunicative motion,
enabling further inquiry into neural bases of communication. The requirements for
additional noninvasive methods of data collection and automatic analysis of
natural gesture and sign language are discussed.
PMID- 29342521
TI - An evolutionary approach to sign language emergence: From state to process.
AB - Understanding the relationship between gesture, sign, and speech offers a
valuable tool for investigating how language emerges from a nonlinguistic state.
We propose that the focus on linguistic status is problematic, and a shift to
focus on the processes that shape these systems serves to explain the
relationship between them and contributes to the central question of how language
evolves.
PMID- 29342522
TI - Language readiness and learning among deaf children.
AB - We applaud Goldin-Meadow & Brentari's (G-M&B's) significant efforts to consider
the linkages between sign, gesture, and language. Research on deaf children and
sign language acquisition can broaden the G-M&B approach by considering how
language readiness is also a social phenomenon and that distinctions between
imagistic and categorical formats rely on language practices and contexts.
PMID- 29342523
TI - Same or different: Common pathways of behavioral biomarkers in infants and
children with neurodevelopmental disorders?
AB - The extent to which early motor patterns represent antecedents to later
communicative functions, and the emergence of gesture and/or sign as potential
communicative acts in neurodevelopmental disorders (NDDs), are research questions
that have received recent attention. It is important to keep in mind that
different NDDs have different neurological underpinnings, with correspondingly
different implications for their conceptualization, detection, and treatment.
PMID- 29342524
TI - Are gesture and speech mismatches produced by an integrated gesture-speech
system? A more dynamically embodied perspective is needed for understanding
gesture-related learning.
AB - We observe a tension in the target article as it stresses an integrated gesture
speech system that can nevertheless consist of contradictory representational
states, which are reflected by mismatches in gesture and speech or sign. Beyond
problems of coherence, this prevents furthering our understanding of gesture
related learning. As a possible antidote, we invite a more dynamically embodied
perspective to the stage.
PMID- 29342525
TI - Toward true integration.
AB - Whether in sign or speech, language is more integrative than the target article
suggests. A more integrative view embraces not only sign/speech and co
sign/speech gesture, but also indicative gestures irrespective of modality, and
locations along with movements in the signed modality, as suggested by both
linguistic acquisition and pathologies. An extended integrative view also proves
advantageous in terms of conceptual coherence.
PMID- 29342526
TI - Vocal laughter punctuates speech and manual signing: Novel evidence for similar
linguistic and neurological mechanisms.
AB - Vocal laughter fills conversations between speakers with normal hearing and
between deaf users of American Sign Language, but laughter rarely intrudes on the
phrase structure of spoken or signed conversation, being akin to punctuation in
written text. This punctuation effect indicates that language, whether vocal or
signed, is dominant over laughter, and that speech and manual signing involve
similar mechanisms.
PMID- 29342527
TI - Iconic enrichments: Signs vs. gestures.
AB - Semantic work on sign language iconicity suggests, as do Goldin-Meadow & Brentari
(G-M&B) in their target article, that "sign should be compared with speech-plus
gesture, not speech alone" (sect. 7.1). One key question is whether speech-plus
gesture and sign-with-iconicity really display the same expressive resources.
This need not be the case, because gestural enrichments are typically not at
issue, whereas iconic enrichments in sign language can often be at-issue. Future
research should thus focus on the "projection" properties of different sorts of
iconic enrichment in both modalities.
PMID- 29342528
TI - Gestures can create diagrams (that are neither imagistic nor analog).
AB - The claim that gesture is primarily imagistic, analog, and holistic is challenged
by the presence of abstract diagrammatic gestures, here points and lines, that
represent point-like and line-like concepts and are integrated into larger
constituents.
PMID- 29342529
TI - Gesture and language: Distinct subsystem of an integrated whole.
AB - The commentaries have led us to entertain expansions of our paradigm to include
new theoretical questions, new criteria for what counts as a gesture, and new
data and populations to study. The expansions further reinforce the approach we
took in the target article: namely, that linguistic and gestural components are
two distinct yet integral sides of communication, which need to be studied
together.
PMID- 29342530
TI - Pros and cons of blurring gesture-language lines: An evolutionary linguistic
perspective.
AB - The target article's emphasis on distinguishing sign from gesture may resolve one
important objection to gesture-first theories of language evolution. However,
this approach risks undervaluing the gradual progression from nonlanguage to
language over hominin evolution, and in emerging sign systems today. I call for
less emphasis on drawing boundaries and more emphasis on understanding the
processes of change.
PMID- 29342531
TI - Good things come in threes: Communicative acts comprise linguistic, imagistic,
and modifying components.
AB - Gesture and sign form an integrated communication system, as do gesture and
speech. Communicative acts in both systems combine categorical linguistic (words
or signs) with imagistic (gestures) components. Additionally, both sign and
speech can employ modifying components that convey iconic information tied to a
linguistic base morpheme. An accurate analysis of communicative acts must take
this third category into account.
PMID- 29342532
TI - The influence of communication mode on written language processing and beyond.
AB - Empirical evidence suggests a broad impact of communication mode on cognition at
large, beyond language processing. Using a sign language since infancy might
shape the representation of words and other linguistic stimuli - for example,
incorporating in it the movements and signs used to express them. Once integrated
into linguistic representations, this visuo-motor content can affect deaf
signers' linguistic and cognitive processing.
PMID- 29342533
TI - Where does (sign) language begin?
AB - Goldin-Meadow & Brentari (G-M&B) outline several criteria for delineating the
boundaries between (discrete) signs and (continuous) gestures. However, the
complex links between linguistics forms and their phonetic realizations defy such
heuristics. A systematic exploration of language structure by mouth and by hand
may help get us closer to answering the important challenge outlined in this
target article.
PMID- 29342534
TI - The physiognomic unity of sign, word, and gesture.
AB - Goldin-Meadow & Brentari (G-M&B) are implicitly going against the dominant
paradigm in language research, namely, the "speech as written language" metaphor
that portrays vocal sounds and bodily signs as means of delivering stable word
meanings. We argue that Heinz Werner's classical research on the physiognomic
properties of language supports and complements their view of sign and gesture as
a unified system.
PMID- 29342535
TI - What is a gesture? A lesson from comparative gesture research.
AB - Research into nonhuman primates' gestures is often limited by the lack of clear
criteria to define a gesture and by studying gestures separately from other
communicative means. Despite the fundamental differences between the gestural
communication of humans and other primates, I argue that sign language research
might benefit from the lessons learned from these drawbacks and the current
developments in primate communication research.
PMID- 29342536
TI - Why would the discovery of gestures produced by signers jeopardize the
experimental finding of gesture-speech mismatch?
AB - Mismatch occurs when there is a discrepancy between produced gestures and co
occurring speech. In this commentary, I explore why research on mismatch might be
called into question by changing views of what constitutes a gesture. I argue
that the experimental procedure for producing mismatch, through its coding
methods, is blind to the tight temporal coordination of gesture and affiliated
talk.
PMID- 29342537
TI - The categorical role of structurally iconic signs.
AB - Goldin-Meadow & Brentari (G-M&B) argue that, for sign language users, gesture -
in contrast to linguistic sign - is iconic, highly variable, and similar to
spoken language co-speech gesture. We discuss two examples (telicity and absolute
gradable adjectives) that challenge the use of these criteria for distinguishing
sign from gesture.
PMID- 29342538
TI - Gesture or sign? A categorization problem.
AB - Goldin-Meadow & Brentari (G-M&B) rely on a formalist approach to language,
leading them to seek objective criteria by which to distinguish language and
gesture. This results in the assumption that gradient aspects of signs are
gesture. Usage-based theories challenge this view, maintaining that all
linguistic units exhibit gradience. Instead, we propose that the distinction
between language and gesture is a categorization problem.
PMID- 29342539
TI - Pragmatic prospection emphasizes utility of predicting rather than mere
predictability.
AB - Contrary to one assumption of CLASH, we suggest that colder rather than warm
climates are the harsh, unpredictable ones, thus requiring greater self-control.
We propose shifting emphasis from predictability to utility of prediction.
Northern climates may be less predictable than tropical ones, making predictions
and planning far more important, insofar as they can prevent fatalities and
promote other pragmatic benefits.
PMID- 29342540
TI - A climate of confusion.
AB - I identify two confusions and omissions in the target article. Confusion arises
from failure to distinguish between a genetically transmitted adaptation and a
conditional response to the environment, and from the elision of individual and
societal adaptations. Despite points of similarity, there is no mention of
Rushton's controversial theory of the climatic basis of race differences in
violent crime. Sex differences are also ignored.
PMID- 29342541
TI - The CLASH model lacks evolutionary and archeological support.
AB - Data from archaeology and paleoanthropology directly challenge the validity of
the basic assumptions of the CLASH model. By not incorporating a "deep time"
perspective, the hypothesis lacks the evolutionary baseline the authors seek to
infer in validating the model.
PMID- 29342542
TI - Dimensions of environmental risk are unique theoretical constructs.
AB - Life history theory serves as the foundation for the CLimate, Aggression, and
Self-control in Humans (CLASH) model of aggression. However, this model embodies
several misunderstandings of life history constructs and principles. The CLASH
model does not recognize that environmental harshness and environmental
unpredictability are unique theoretical constructs, rendering predictions and
implications from the model suspect.
PMID- 29342543
TI - Using foresight to prioritise the present.
AB - Planning for the future may encourage apparently "impulsive" behaviour when the
future is anticipated to be bleak. Thus, a seeming failure of self-control in
reactive violence could be caused not by a disinclination to plan ahead, but by
virtue of this ability. Furthermore, we point to empirical and theoretical
shortcomings in the authors' case, such as a failure to distinguish proximate and
ultimate explanations.
PMID- 29342544
TI - CLASH's life history foundations.
AB - We recommend extending CLASH by incorporating two evolutionary accounts of the
shift toward fast life histories under harsh, unpredictable conditions. These
accounts, if integrated with CLASH, make different predictions about the
distributions of aggression and violence within and between societies. We discuss
these predictions and propose ways of testing them.
PMID- 29342545
TI - Does distance from the equator predict self-control? Lessons from the Human
Penguin Project.
AB - We comment on the proposition "that lower temperatures and especially greater
seasonal variation in temperature call for individuals and societies to adopt ...
a greater degree of self-control" (Van Lange et al., sect. 3, para. 4) for which
we cannot find empirical support in a large data set with data-driven analyses.
After providing greater nuance in our theoretical review, we suggest that Van
Lange et al. revisit their model with an eye toward the social determinants of
self-control.
PMID- 29342546
TI - More than just climate: Income inequality and sex ratio are better predictors of
cross-cultural variations in aggression.
AB - Van Lange et al. argue that variations in climate explain cross-societal
variations in violence. We suggest that any approach seeking to understand cross
cultural variation in human behavior via an ecological framework must consider a
wider array of ecological variables, and we find that income inequality and sex
ratio are better predictors than climate of cross-societal variations in
violence.
PMID- 29342547
TI - Climate is not a good candidate to account for variations in aggression and
violence across space and time.
AB - We agree with Van Lange et al. that climate is likely to affect individuals'
social behavior in many ways. However, we suspect that its impact on physiology
and psychology is so remote that its predictive power disintegrates almost
completely through the causal chain underlying aggression and violence.
PMID- 29342548
TI - Postcolonial geography confounds latitudinal trends in observed aggression and
violence.
AB - To support their hypothesis, the authors point to an inverse correlation between
latitude and the incidence of civil conflict and crime. This observation cannot
be accepted as evidence for the hypothesis, because of a weighty confounding
variable: the historical geography of colonialism and its effects on the
fragility of nations.
PMID- 29342549
TI - The role of adolescence in geographic variation in violent aggression.
AB - In explaining variation in violent aggression across populations, the age
structures of those populations must be considered. Adolescents between the ages
of 15 and 25 are disproportionately responsible for violent aggression in every
society, and increases in violence tend to follow population "youth bulges."
Large numbers of adolescents in equatorial regions may account for observed
relationships between geography and violence.
PMID- 29342550
TI - The paradoxical effect of climate on time perspective considering resource
accumulation.
AB - Considering purely climate, southern countries are less harsh and more
predictable than northern countries. From a historical perspective, freezing
winters resulting in fewer available resources contribute to the development of
strong future orientation. The paradox is that future orientation contributes to
accumulation of resources in the long run, making individuals' immediate living
conditions less harsh, leading to slower life strategies.
PMID- 29342551
TI - The CLASH model in broader life history context.
AB - In this commentary, we address two questions: (1) Is the drive in many young men
to gain status and amass resources, which frequently entails direct competition
with members of outgroups, one of the key variables underlying the CLASH model?
(2) Why is there so much variation in reactive aggression/violence between people
living in the same environment?
PMID- 29342552
TI - An alternative interpretation of climate data: Intelligence.
AB - The CLASH model proposed in the target article is plausible but less than
parsimonious. I suggest that statistical analysis probably would find slower life
history strategy, greater focus on the future, and greater self-control to be
highly correlated and perhaps unifactorial, because they are all manifestations
of a single underlying variable, namely, intelligence. I suggest how intelligence
as a state variable plausibly could explain the differences observed by the
authors.
PMID- 29342553
TI - Sociocultural discourse in science: Flawed assumptions and bias in the CLASH
model.
AB - In this commentary, we contest Van Lange and colleagues' central claim that
"countries closer to the equator are generally more violent." We point to the
lack of credible empirical evidence for this assertion and suggest that the CLASH
model uses the language of science to lend false credibility to a problematic
sociocultural discourse.
PMID- 29342554
TI - Bullying when it's hot? The CLASH model and climatic influences on bullying.
AB - A novel predictor of bullying may be underlying regional weather conditions
(i.e., climate). Bullying data support the CLASH model of aggression by
suggesting that climate may moderate the forms and severity of bullying, as well
as predict its prevalence across countries. Furthermore, bullying data also
suggest that the CLASH model may apply to forms of aggression beyond reactive
aggression.
PMID- 29342555
TI - Hell on earth? Equatorial peaks of heat, poverty, and aggression.
AB - Van Lange et al.'s global CLASH model overemphasizes climatic origins and
underemphasizes economic origins of aggression. Our 167-country analysis of
latitudinal gradients of heat, poverty, and aggression finds that heat-induced
aggression is mediated by poverty and that heat tempers rather than fuels poverty
induced aggression. More importantly, the CLASH model hints at latitudinal,
equatorial, and hemispheric upgradings of climato-economic modeling of human
behavior.
PMID- 29342556
TI - Culture matters for life history trade-offs.
AB - Van Lange et al. add important life history perspectives to understanding
violence. However, direct links between climate and violence are unlikely because
cultural institutions modify human responses. Examples are given from the Bushmen
of the Kalahari and Enga of Papua New Guinea. The correlations identified may
occur because many countries closer to the equator are caught in the gap between
the demise of traditional cultural institutions and the rise of modern forms of
governance.
PMID- 29342557
TI - Reply to Van Lange et al.: Proximate and ultimate distinctions must be made to
the CLASH model.
AB - Transcending reviewed proximate theories, Van Lange et al.'s CLASH model attempts
to ultimately explain the poleward declension of aggression and violence.
Seasonal cold is causal, but, we contend, principally as an ecologically relevant
evolutionary pressure. We further argue that futurity and restraint are life
history variables, and that Life History Theory evolutionarily explains the
biogeography of aggression and violence as strategic adaptation.
PMID- 29342558
TI - Where the psychological adaptations hit the ecological road.
AB - We argue that the target authors focus too much on adaptive behavioral responses
and not enough on actual psychological adaptations. We suggest the Dark Triad
traits may represent facultative, psychological adaptations sensitive to seasonal
variance and food shortages. We document that shorter distances from the equator
are linked to higher national narcissism levels, whereas longer distances are
associated with higher national-level machiavellianism. Dark Triad traits may
serve as critical survival mechanisms when prioritizing oneself over and/or at
the cost of others.
PMID- 29342559
TI - Stuck in the heat or stuck in the hierarchy? Power relations explain regional
variations in violence.
AB - We contend that an ecological account of violence and aggression requires
consideration of societal and cultural settings. Focusing on hierarchical
relations, we argue countries with higher (vs. lower) power distance are, on
average, located closer to the equator, have more challenging climates (e.g.,
higher temperature; lower temperature variation), and have a greater prevalence
of violence and aggression (e.g., higher homicide rates).
PMID- 29342560
TI - Why the CLASH model is an unconvincing evolutionary theory of crime.
AB - The CLASH model is not convincing for two reasons. First, it ignores prior
research proposing very similar ideas in a more compelling fashion. Second, it
dismisses the role of genetic factors in shaping criminal propensities across
population groups, opting for a facultative view of life history evolution that
does not seem to square with current evidence.
PMID- 29342561
TI - The importance of being explicit.
AB - Van Lange et al. propose that climate affects violence via its effects on life
history. That much is reasonable (and not novel), but their theory lacks causal
specificity. Their foundational claim of an association between heat and violence
is not well documented, and several findings that the authors themselves cite
seem inconsistent with their model, rather than supportive.
PMID- 29342562
TI - Warm coffee, sunny days, and prosocial behavior.
AB - This commentary discusses the research finding that warmer temperatures are
associated with more prosocial outcomes. It calls for future research and theory
on climate-related variables and social behavior to allow for both positive and
negative emotional and behavioral responses to warmer temperatures.
PMID- 29342563
TI - Russian data refute the CLASH model.
AB - We examined the CLASH model using the data on climate and violence from the
Russian Federation. The Russian Federation is a huge country with dramatic
climatic differences between regions. Our results are absolutely inconsistent
with the model. We consider there are a range of climates in which the human
organism functions optimally. Deviations from the range cause impulsiveness and
aggression.
PMID- 29342564
TI - The role of climate in human aggression and violence: Towards a broader
conception.
AB - The psychological processes that predict aggressive behaviour are also typically
associated with violent self-harm (e.g., poor self-control). Yet, although human
violence (towards others) appears to increase with proximity to the equator,
suicide rates tend to decrease. In the light of this empirical puzzle, I argue
that Van Lange et al.'s CLASH model would benefit from a broader
conceptualization of human aggression.
PMID- 29342565
TI - The Logic of Climate and Culture: Evolutionary and Psychological Aspects of
CLASH.
AB - A total of 80 authors working in a variety of scientific disciplines commented on
the theoretical model of CLimate, Aggression, and Self-control in Humans (CLASH).
The commentaries cover a wide range of issues, including the logic and
assumptions of CLASH, the evidence in support of CLASH, and other possible causes
of aggression and violence (e.g., wealth, income inequality, political
circumstances, historic circumstances, pathogen stress). Some commentaries also
provide data relevant to CLASH. Here we clarify the logic and assumptions of
CLASH and discusses its extensions and boundary conditions. We also offer
suggestions for future research. Regardless of whether none, some, or all of
CLASH is found to be true, we hope it will stimulate future research on the link
between climate and human behavior. Climate is one of the most presing issues of
our time.
PMID- 29342566
TI - Aggression, predictability of the environment, and self-regulation:
Reconciliation with animal research.
AB - Apparently inconsistent with the CLASH model, animal research relates predictable
environments to rigid routine behaviors and aggression. However, our work on
evolutionary and neural adaptations to (un)predictable environments may be able
to reconcile the CLASH model with the animal research, but also suggests
complexities beyond the dichotomous approach of CLASH.
PMID- 29342567
TI - Inconsistent with the data: Support for the CLASH model depends on the wrong kind
of latitude.
AB - We argue that the CLASH model makes a number of questionable assumptions about
the harshness and unpredictability of low-latitude environments, calling into
question the life history strategy approach used, and that it is inconsistent
with more nuanced global patterns of violence. We suggest an alternative account
for less violence at high latitudes, based on a greater need for cooperation.
PMID- 29342568
TI - Mapping multiple drivers of human obesity.
AB - The insurance hypothesis is a reasonable explanation for the current obesity
epidemic. One alternative explanation is that the marketing of high-sugar foods,
especially sugar-sweetened beverages, drives the rise in obesity. Another
prominent hypothesis is that obesity spreads through social influence. We offer a
framework for estimating the extent to which these different models explain the
rise in obesity.
PMID- 29342569
TI - Eating and body image: Does food insecurity make us feel thinner?
AB - Body image distortions are common in healthy individuals and a central aspect of
serious clinical conditions, such as eating disorders. This commentary explores
the potential implications of body image and its distortions for the insurance
hypothesis. In particular, we speculate that body image may be an intervening
variable mediating the relationship between perceived food scarcity and eating
behavior.
PMID- 29342570
TI - Expanding the insurance hypothesis of obesity with physiological cues.
AB - Food insecurity relates to fat storage, but cannot explain fat storage in excess
of levels optimal for buffering - that is, obesity. However, factors related to
food unpredictability in the past, including stress, disease, micronutrient
content of food, and physical activity, may cue physiological processes that
change intake or fat deposition even in the absence of actual food
unpredictability.
PMID- 29342571
TI - Epidemiological foundations for the insurance hypothesis: Methodological
considerations.
AB - Nettle et al. evaluate evidence for the insurance hypothesis, which links obesity
with the perception of food scarcity. Epidemiological findings in this area have
generally been weak and inconsistent. The present commentary examines three key
methodological issues arising from the literature on the association between
obesity and the perception of food scarcity in humans, with suggestions for
future epidemiological research.
PMID- 29342572
TI - The life history model of the insurance hypothesis.
AB - Nettle et al.'s explanation based on the insurance hypothesis applies only to the
association between food insecurity and body weight among adult women, but not to
the results about there being no such associations among adult men and children.
These results may be best understood when the insurance hypothesis is integrated
with the life history model.
PMID- 29342573
TI - Episodic memory as an explanation for the insurance hypothesis in obesity.
AB - In evaluating the insurance hypothesis as an explanation for obesity, we propose
one missing piece of the puzzle. Our suggested explanation for why individuals
report food insecurity is that an individual may have an impaired episodic
ability to plan for the future.
PMID- 29342574
TI - Toward a mechanistic understanding of the impact of food insecurity on obesity.
AB - Nettle et al. provide a useful but incomplete analysis of the drivers of obesity.
In this commentary, we argue that a dual-motives conceptualization of self
control, together with insights from the psychology of (perceived and actual)
scarcity, might help advance a more fine-grained mechanistic understanding of the
observed association between food insecurity and obesity.
PMID- 29342575
TI - Appraising food insecurity.
AB - This commentary focuses on the mechanisms underlying the appraisal of food
insecurity. I first describe what appraisal is and why it plays a major role in
explaining how different individuals consider food supply as more or less secure.
I then describe the potential reciprocal links between appraisal and obesity,
based on the well-documented evidence that obesity can cause cognitive deficits.
PMID- 29342576
TI - Implicit attitudes, eating behavior, and the development of obesity.
AB - Nettle et al. describe increasing food intake (relative to energy expenditure) in
response to food insecurity as a key contributor to obesity. I argue that a
variety of implicit psychological mechanisms underlie this process to contribute
to weight gain. The biobehavioral pathways and the social nature of food
selection discussed here are importantly related to food selection and obesity.
PMID- 29342577
TI - A life-history theory perspective on obesity.
AB - We extend Nettle et al.'s insurance hypothesis (IH) argument, drawing upon life
history theory (LHT), a developmental evolutionary perspective that documents
downstream consequences of early-life exposure to unpredictable environments. We
discuss novel evidence consistent with both IH and LHT, suggesting that early
life exposure to unpredictable environments is associated with reduced engagement
in weight management behaviors and a greater probability of adulthood obesity.
PMID- 29342578
TI - Potential psychological accounts for the relation between food insecurity and
body overweight.
AB - We suggest two psychological mechanisms, temporal discounting and feeling of
resource scarcity, for explaining the relation between food insecurity and body
overweight. We demonstrate how Nettle et al.'s findings could be explained, post
hoc, by each of these accounts, suggesting that their data are not rich enough to
allow identification of mechanisms that underlie food insecurity and overweight
relationship.
PMID- 29342579
TI - Predicting human adiposity - sometimes - with food insecurity: Broaden the model
for better accuracy.
AB - The target article explores the role of food insecurity as a contemporary risk
factor for human overweight and obesity. The authors provide conditional support
for the insurance hypothesis among adult women from high-income countries. We
consider the potential contribution of additional factors in producing variation
in adiposity patterns between species and across human contexts.
PMID- 29342580
TI - Social nature of eating could explain missing link between food insecurity and
childhood obesity.
AB - We suggest that social factors are key to explain the missing link between food
insecurity and obesity in children. Parents and public institutions are
children's nutritional gatekeepers. They protect children from food insecurity by
trimming down their consumption or by institutional support. To gauge children's
food insecurity, evaluations across the different nutritional gatekeepers need to
be integrated.
PMID- 29342581
TI - A game theory appraisal of the insurance hypothesis: Specific polymorphisms in
the energy homeostasis network as imprints of a successful minimax strategy.
AB - The existence of specific polymorphisms in genes of key hormones of the energy
homeostasis network that have been shown to predispose to obesity and the so
called metabolic syndrome provides further biological support for the proposed
insurance hypothesis. In a broader sense, such polymorphisms can be understood as
biological imprints of an evolutionarily successful minimax strategy employed by
ancient Homo sapiens subpopulations in a one-player game against nature.
PMID- 29342582
TI - Towards a behavioural ecology of obesity.
AB - Addressing the obesity epidemic depends on a holistic understanding of the
reasons that people become and maintain excessive fat. Theories about the causes
of obesity usually focus proximately or evoke evolutionary mismatches, with
minimal clinical value. There is potential for substantial progress by adapting
strategic body mass regulation models from evolutionary ecology to human obesity
by assessing the role of information.
PMID- 29342583
TI - Anti-fat discrimination in marriage more clearly explains the poverty-obesity
paradox.
AB - The target article proposes the insurance hypothesis as an explanation for higher
levels of obesity among food-insecure women living in high-income countries. An
alternative hypothesis based on anti-fat discrimination in marriage can also
account for such correlations between poverty and obesity and is more consistent
with finer-grained analyses by marital status, gender, and age.
PMID- 29342584
TI - Committed to the insurance hypothesis of obesity.
AB - Can ideas about the regulation of body mass in birds be used to explain the
breakdown of regulation associated with obesity and anorexia in humans? There is
no evidence to think so. Medicine can always benefit from the application of
evolutionary ecology ideas, but we must be prepared to dismiss these ideas when
they just do not fit the data.
PMID- 29342585
TI - "It's a bit more complicated than that": A broader perspective on determinants of
obesity.
AB - The insurance hypothesis does not address important factors known to contribute
to obesity levels in all persons, not just adult women in the industrialized
world. These include psychological determinants of eating behaviours, the decline
in physical activity leading to a negative energy balance, the dense built
environment, pervasive food marketing, and the increased availability of energy
dense, nutrient-poor food.
PMID- 29342586
TI - Anorexia: A perverse effect of attempting to control the starvation response.
AB - Starvation arouses evolved protective mechanisms including binge eating and
increased metabolic efficiency and fat storage. When aroused by dieting, the
experiences of out-of-control eating, increased appetite, and increased fat
storage arouse greater fears of obesity, spurring renewed attempts to restrict
intake severely. The resulting positive feedback cycle escalates into bulimia for
many, and anorexia in a few.
PMID- 29342587
TI - Obesity as self-regulation failure: A "disease of affluence" that selectively
hits the less affluent?
AB - An effect of the long-term cycle of industrial and post-industrial global
development is the increasingly generalized access to abundant and diversified
food sources. This poses a substantial problem of self-regulation that mainly
affects the less affluent and whose failures may play an important role in the
explanation of the increasing social incidence of overweight and obesity
problems.
PMID- 29342588
TI - Obesity is not just elevated adiposity, it is also a state of metabolic
perturbation.
AB - Nettle et al. miss the crucial difference between adaptive models of storing
energy and explanations for the pathological metabolic state of obesity. I
suggest that the association of food insecurity with obesity in women from
industrialized settings is most likely due to reverse causation: Poverty reduces
agency to resist obesogenic foods, and this scenario is compounded by
perturbations of insulin metabolism stemming from high adiposity and lipogenic
diets.
PMID- 29342589
TI - Using food insecurity in health prevention to promote consumer's embodied self
regulation.
AB - Health messages designed to address obesity are typically focused on the long
term benefits of eating healthy food. However, according to the insurance
hypothesis, obese people are food insecure, and this causes them to be overly
concerned about short-term consumption. As such, it is necessary to rethink
public health messaging and consider how to reduce short-term insecurity by
eating healthy food.
PMID- 29342590
TI - Household-level financial uncertainty could be the primary driver of the global
obesity epidemic.
AB - Evidence has accumulated in support of the notion that changes in household-level
financial uncertainty (or "economic insecurity") may be an important fundamental
cause of the global obesity epidemic. The timing and spatial/demographic
incidence of the obesity epidemic suggest that economic policies aimed at
expanding economic freedom may have inadvertently shifted risk to households,
thereby generating a costly public health problem.
PMID- 29342591
TI - Children respond to food restriction by increasing food consumption.
AB - Consistent with the insurance hypothesis, research shows that when children
experience restricted access to food, they display increased intake when
restrictions are lifted. This effect appears more robust for girls compared to
boys, and for children with lower levels of inhibitory control. The insurance
hypothesis has potentially important implications for parental feeding practices.
PMID- 29342592
TI - Adaptive principles of weight regulation: Insufficient, but perhaps necessary,
for understanding obesity.
AB - We reflect on the major issues raised by a thoughtful and diverse set of
commentaries on our target article. We draw attention to the need to
differentiate between ultimate and proximate explanation; the insurance
hypothesis (IH) needs to be understood as an ultimate-level argument, although we
welcome the various suggestions made about proximate mechanisms. Much of this
response is concerned with clarifying the interrelationships between
adaptationist explanations like the IH, constraint explanations, and dysfunction
explanations, in understanding obesity. We also re-examine the empirical evidence
base, concurring that it is equivocal and only partially supportive. Several
commentators offer additional supporting evidence, whereas others propose
alternative explanations for the evidence we reviewed and suggest ways that our
current knowledge could be strengthened. Finally, we take the opportunity to
clarify some of the assumptions and predictions of our formal model.
PMID- 29342593
TI - Parallel attentive processing and pre-attentive guidance.
AB - This commentary focuses on two related, open questions in Hulleman & Olivers'
(H&O's) proposal: (1) the nature of the parallel attentive process that
determines target presence within, and thus presumably the size of, the
functional visual field, and (2) how the pre-attentive guidance mechanism must be
conceived to also account for search performance in tasks that afford no reliable
target-based guidance.
PMID- 29342594
TI - "Target-absent" decisions in cancer nodule detection are more efficient than
"target-present" decisions!
AB - Many parts of the medical image are never fixated when a radiologist searches for
cancer nodules. Experts are able to use peripheral vision very efficiently. The
size of the functional visual field appears to increase according to the level of
expertise. However, searching a medical image diverges, in a puzzling way, from
the typical search for a target feature in the laboratory.
PMID- 29342595
TI - Contextual and social cues may dominate natural visual search.
AB - A framework where only the size of the functional visual field of fixations can
vary is hardly able to explain natural visual-search behavior. In real-world
search tasks, context guides eye movements, and task-irrelevant social stimuli
may capture the gaze.
PMID- 29342596
TI - An appeal against the item's death sentence: Accounting for diagnostic data
patterns with an item-based model of visual search.
AB - We show that our item-based model, competitive guided search, accounts for the
empirical patterns that Hulleman & Olivers (H&O) invoke against item-based
models, and we highlight recently reported diagnostic data that challenge their
approach. We advise against "forsaking the item" unless and until a full fixation
based model is shown to be superior to extant item-based models.
PMID- 29342597
TI - Chances and challenges for an active visual search perspective.
AB - Using fixations as the fundamental unit of visual search is an appealing gear
change in a paradigm that has long dominated attention research. To truly inform
theories of search, however, additional challenges must be faced, including (1)
an empirically motivated definition of fixation in the presence of fixational
saccades and (2) the biases and limitations of transsaccadic perception and
memory.
PMID- 29342598
TI - Mathematical fixation: Search viewed through a cognitive lens.
AB - We provide a mathematical category theory account of the size and location of the
authors' Functional View Field (FVF). Category theory explains systematic
cognitive ability via universal construction, that is, a necessary and sufficient
condition for composition of cognitive processes. Similarly, FVF size and
location is derived from a (universal) construction called a fibre (pullback)
bundle.
PMID- 29342599
TI - Those pernicious items.
AB - Hulleman & Olivers (H&O) identify a number of problems with item-based thinking
and its impact on our understanding of visual search. I detail ways in which item
thought is worse than the authors suggest. I concur with the broad strokes of the
theory they set out, and also clarify the relationship between their view and our
recent theory of visual search.
PMID- 29342600
TI - Where the item still rules supreme: Time-based selection, enumeration, pre
attentive processing and the target template?
AB - I propose that there remains a central role for the item (or its equivalent) in a
wider range of search and search-related tasks/functions than might be conveyed
by the article. I consider the functional relationship between the framework and
some aspects of previous theories, and suggest some challenges that the new
framework might encounter.
PMID- 29342601
TI - "I am not dead yet!" - The Item responds to Hulleman & Olivers.
AB - The item can only be dispensed within artificial tasks that, although useful in
the lab, do not reflect the real world. There, the attended item is the goal of
search. Hulleman & Olivers' (H&O's) model can ignore the item only by reducing
search to the question of whether a patch of 0s (distractors) contains a 1
(target).
PMID- 29342602
TI - Task implementation and top-down control in continuous search.
AB - Evidence from continuous search suggests that targets are detected by default,
whereas distractors are processed in considerable depth. These observations shed
light on task implementation and top-down control. Task implementation builds on
forming dynamic distractor models, based on continuous integration of distractor
related information. Top-down control builds on using these models for testing
upcoming stimulus information.
PMID- 29342603
TI - The "item" as a window into how prior knowledge guides visual search.
AB - We challenge the central idea proposed in Hulleman & Olivers (H&O) by arguing
that the "item" is still useful for understanding visual search and for
developing new theoretical frameworks. The "item" is a flexible unit that
represents not only an individual object, but also a bundle of objects that are
grouped based on prior knowledge. Uncovering how the "item" is represented based
on prior knowledge is essential for advancing theories of visual search.
PMID- 29342604
TI - Eye movements are an important part of the story, but not the whole story.
AB - Some previous accounts of visual search have emphasized covert attention at the
expense of eye movements, and others have focused on eye movements while ignoring
covert attention. Both selection mechanisms are likely to contribute to many
searches, and a full account of search will probably need to explain how the two
interact to find visual targets.
PMID- 29342605
TI - Fixations are not all created equal: An objection to mindless visual search.
AB - This call to revolution in theories of visual search does not go far enough.
Treating fixations as uniform is an oversimplification that obscures the critical
role of the mind. We remind readers that what happens during a fixation depends
on mindset, as shown in studies of search strategy and of humans' ability to
rapidly resume search following an interruption.
PMID- 29342606
TI - Analysing real-world visual search tasks helps explain what the functional visual
field is, and what its neural mechanisms are.
AB - Rejecting information-processing-based theory permits the merging of a top-down
analysis of visual search tasks with a bottom-up analysis of brain structure and
function. This reveals the true nature of the functional visual field and its
precise role in the conduct of visual search tasks. The merits of such analyses
over the traditional methods of the authors are described.
PMID- 29342607
TI - Item-based selection is in good shape in visual compound search: A view from
electrophysiology.
AB - We argue that although the framework put forward by Hulleman & Olivers (H&O) can
successfully explain much of visual search behaviour, it appears limited to tasks
without precise target identification demands. In particular, we contend that the
unit of selection may be larger than a single item in standard detection tasks,
whereas the unit may mandatorily be item-based in compound tasks.
PMID- 29342608
TI - Set size slope still does not distinguish parallel from serial search.
AB - Much of the evidence for theories in visual search (including Hulleman & Olivers'
[H&O's]) comes from inferences made using changes in mean RT as a function of the
number of items in a display. We have known for more than 40 years that these
inferences are based on flawed reasoning and obscured by model mimicry. Here we
describe a method that avoids these problems.
PMID- 29342609
TI - The FVF framework and target prevalence effects.
AB - The Functional Visual Field (FVF) offers explanatory power. To us, it relates to
existing literature on the flexibility of attentional focus in visual search and
reading (Eriksen & St. James 1986; McConkie & Rayner 1975). The target article
promotes reflection on existing findings. Here we consider the FVF as a mechanism
in the Prevalence Effect (PE) in visual search.
PMID- 29342610
TI - Scanning movements during haptic search: similarity with fixations during visual
search.
AB - Finding relevant objects through vision, or visual search, is a crucial function
that has received considerable attention in the literature. After decades of
research, data suggest that visual fixations are more crucial to understanding
how visual search works than are the attributes of stimuli. This idea receives
further support from the field of haptic search.
PMID- 29342611
TI - Feature integration, attention, and fixations during visual search.
AB - We argue that mechanistic premises of "item-based" theories are not invalidated
by the fixation-based approach. We use item-based theories to propose an account
that does not advocate strict serial item processing and integrates fixations.
The main focus of this account is feature integration within fixations. We also
suggest that perceptual load determines the size of the fixations.
PMID- 29342612
TI - The FVF might be influenced by object-based attention.
AB - Hulleman & Olivers (H&O) argue that the primary unit in search should be
fixations, and in doing so posit a Functional View Field (FVF). There is evidence
from the object-based visual attention literature that the FVF may not process
visual information uniformly. Here I sketch how object-based attention may
influence processing within the FVF as well as the shape of the FVF.
PMID- 29342613
TI - On the brink: The demise of the item in visual search moves closer.
AB - We proposed to abandon the item as conceptual unit in visual search and adopt a
fixation-based framework instead. We treat various themes raised by our
commentators, including the nature of the Functional Visual Field and existing
similar ideas, alongside the importance of items, covert attention, and top
down/contextual influences. We reflect on the current state of, and future
directions for, visual search.
PMID- 29342614
TI - Searching for unity: Real-world versus item-based visual search in age-related
eye disease.
AB - When studying visual search, item-based approaches using synthetic targets and
distractors limit the real-world applicability of results. Everyday visual search
can be impaired in patients with common eye diseases like glaucoma and age
related macular degeneration. We highlight some results in the literature that
suggest assessment of real-word search tasks in these patients could be
clinically useful.
PMID- 29342615
TI - Gaze-contingent manipulation of the FVF demonstrates the importance of fixation
duration for explaining search behavior.
AB - Hulleman & Olivers' (H&O's) model introduces variation of the functional visual
field (FVF) for explaining visual search behavior. Our research shows how the FVF
can be studied using gaze-contingent displays and how FVF variation can be
implemented in models of gaze control. Contrary to H&O, we believe that fixation
duration is an important factor when modeling visual search behavior.
PMID- 29342616
TI - Oh, the number of things you will process (in parallel)!
AB - We highlight the importance of considering the variance produced during the
parallel processing stage in vision and present a case for why it is useful to
consider the "item" as a meaningful unit of study when investigating early visual
processing in visual search tasks.
PMID- 29342617
TI - What fixations reveal about oculomotor scanning behavior in visual search.
AB - Hulleman & Olivers' (H&O's) conceptual framework does not consider variation of
fixation duration and its interaction with the size of the functional viewing
field (FVF). Here we provide empirical evidence of a dynamic interaction between
the two parameters, suggesting that fixations, as the central unit in H&O's
framework, should be studied on both the spatial and temporal dimensions.
PMID- 29342618
TI - Why the item will remain the unit of attentional selection in visual search.
AB - Hulleman & Olivers (H&O) reject item-based serial models of visual search, and
they suggest that items are processed equally and globally during each fixation
period. However, neuroscientific studies have shown that attentional biases can
emerge in parallel but in a spatially selective item-based fashion. Even within a
parallel architecture for visual search, the item remains the critical unit of
selection.
PMID- 29342619
TI - Until the demise of the functional field of view.
AB - Hulleman & Olivers (H&O) make a much-needed stride forward for a better
understanding of visual search behavior by rejecting theories based on discrete
stimulus items. I propose that the framework could be further enhanced by clearly
delineating distinct mechanisms for attention guidance, selection, and
enhancement during visual search, instead of conflating them into a single
functional field of view.
PMID- 29342620
TI - How functional are functional viewing fields?
AB - Hulleman & Olivers' (H&O's) proposal is a refreshing addition to the visual
search literature. Although we like their proposal that fixations, not individual
items should be considered a fundamental unit in visual search, we point out some
unresolved problems that their account will have to solve. Additionally, we
consider predictions that can be made from the account, in particular in relation
to priming of visual search, finding that the account generates interesting
testable predictions.
PMID- 29342621
TI - Don't admit defeat: A new dawn for the item in visual search.
AB - Even though we lack a precise definition of "item," it is clear that people do
parse their visual environment into objects (the real-world equivalent of items).
We will review evidence that items are essential in visual search, and argue that
computer vision - especially deep learning - may offer a solution for the lack of
a solid definition of "item."
PMID- 29342622
TI - Cognitive architecture enables comprehensive predictive models of visual search.
AB - With a simple demonstration model, Hulleman & Olivers (H&O) effectively argue
that theories of visual search need an overhaul. We point to related literature
in which visual search is modeled in even more detail through the use of
computational cognitive architectures that incorporate fundamental perceptual,
cognitive, and motor mechanisms; the result of such work thus far bolsters their
arguments considerably.
PMID- 29342623
TI - Looking further! The importance of embedding visual search in action.
AB - A unified account of visual search in complex everyday environments requires
additional deliberations on the functional grounding of Hulleman & Olivers'
(H&O's) functional viewing field (FVF) model. Their model can accommodate
exploitation of information that is distributed across the immediate environment.
Yet the differences in search between genuinely interacting in the environment
and merely watching it should challenge researchers to look further.
PMID- 29342625
TI - Evidence for a number sense.
AB - Numerosity is inherently confounded by related stimulus attributes such as
density and area, and many studies have reported interactions of various
strengths between area, density, and numerosity. However, direct measurements of
sensitivity within the area-density-numerosity space show that numerosity emerges
as the most spontaneous and sensitive dimension, strongly supporting the
existence of a dedicated number sense.
PMID- 29342624
TI - Infants discriminate number: Evidence against the prerequisite of visual object
individuation and the primacy of continuous magnitude.
AB - Leibovich et al. hypothesize that the absence of visual object individuation
limits infants' numerical skills and necessitates a reliance on continuous
magnitudes. We argue that parallels between infants' numerical discrimination in
the visual and auditory modalities, their abilities to match numerosities across
modalities, and their greater ability to discriminate changes in number compared
with continuous magnitudes contradict the authors' assumptions.
PMID- 29342626
TI - Why try saving the ANS? An alternative proposal.
AB - Leibovich et al. propose that continuous magnitudes and a number sense are used
holistically to judge numerosity. We point out that their proposal is incomplete
and implausible: incomplete, as it does not explain how continuous magnitudes are
calculated; implausible, as it cannot explain performance in estimation tasks. We
propose that we do not possess a number sense. Instead, we assume that numerosity
judgments are accomplished by weighing the different continuous magnitudes
constituting numerosity.
PMID- 29342627
TI - Magnitude, numerosity, and development of number: Implications for mathematics
disabilities.
AB - Leibovich et al. challenge the prevailing view that non-symbolic number sense
(e.g., sensing number the same way one might sense color) is innate, that
detection of numerosity is distinct from detection of continuous magnitude. In
the present commentary, the authors' viewpoint is discussed in light of the
integrative theory of numerical development along with implications for
understanding mathematics disabilities.
PMID- 29342628
TI - Commentary on Leibovich et al.: What next?
AB - The conclusions reached by Leibovich et al. urge the field to regroup and
consider new ways of conceptualizing quantitative development. We suggest three
potential directions for new research that follow from the authors' extensive
review, as well as building on the common ground we can take from decades of
research in this area.
PMID- 29342629
TI - How not to develop a sense of number.
AB - The authors rightly point to the theoretical importance of interactions of space
and number through the life span, yet propose a theory with several weaknesses.
In addition to proclaiming itself unfalsifiable, its stage-like format and
emphasis on the role of selective attention are at odds with what is known about
the development of spatial-numerical associations in infancy.
PMID- 29342630
TI - A "sense of magnitude" requires a new alternative for learning numerical symbols.
AB - Leibovich et al. proposed that the processing of numerosities is based primarily
on a "sense of magnitude." The consequences of this proposal for how numerical
symbols acquire their meaning are, however, neglected. We argue that symbols
cannot be learned by associating them with a system that is not yet able to
derive discrete numbers accurately because of immature cognitive control.
PMID- 29342631
TI - Right idea, wrong magnitude system.
AB - Leibovich et al. claim that number representations are non-existent early in life
and that the associations between number and continuous magnitudes reside in
stimulus confounds. We challenge both claims - positing, instead, that number is
represented independently of continuous magnitudes already in infancy, but is
nonetheless more deeply connected to other magnitudes through adulthood than
acknowledged by the "sense of magnitude" theory.
PMID- 29342632
TI - The contributions of non-numeric dimensions to number encoding, representations,
and decision-making factors.
AB - Leibovich et al. suggest that congruency effects in number perception (biases
towards smaller, denser, etc., dots) are evidence for the number's dependence on
these dimensions. I argue that they fail to differentiate between effects at
three distinct levels of number perception - encoding, representations, and
decision making - and that differentiating between these allows the number to be
independent from, but correlated with, non-numeric dimensions.
PMID- 29342633
TI - Numerical magnitude evaluation as a foundation for decision making.
AB - The evaluation of magnitudes serves as a foundation not only for numerical and
mathematical cognition, but also for decision making. Recent theoretical
developments and empirical studies have linked numerical magnitude evaluation to
a wide variety of core phenomena in decision making and challenge the idea that
preferences are driven by an innate, universal, and stable sense of number or
value.
PMID- 29342634
TI - Direct and rapid encoding of numerosity in the visual stream.
AB - The target article dismisses all prior work purporting to demonstrate that number
is a conceptual primitive. Here, we take issue with their misrepresentation of
our recent line of work on numerosity perception, which demonstrates rapid and
direct encoding of numerosity and undermines the thesis of the target article
that "continuous magnitudes are more automatic and basic than numerosities"
(sect. 1, para. 2).
PMID- 29342635
TI - Numerical intuitions in infancy: Give credit where credit is due.
AB - Leibovich et al. overlook numerous human infant studies pointing to an early
emerging number sense. These studies have carefully manipulated continuous
magnitudes in the context of a numerical task revealing that infants can
discriminate number when extent is controlled, that infants fail to track extent
cues with precision, and that infants find changes in extent less salient than
numerical changes.
PMID- 29342636
TI - Selecting the model that best fits the data.
AB - Leibovich et al. argue that that none of the experiments they review really
establishes that human adults, infants, or nonhuman animals are sensitive to
numerosity independent of a range of continuous quantities. We do not dispute
their claim that the empirical record is inconclusive but argue that model-based
data analysis does offer a way to make progress.
PMID- 29342637
TI - Multitudes are adaptable magnitudes in the estimation of number.
AB - Visual number comparison does not require participants to choose a unit, whereas
units are fundamental to the definition of number. Studies using magnitude
estimation rather than comparison show that number perception is compressed
dramatically past about 20 units. Even estimates of 5-20 items are increasingly
susceptible to effects of visual adaptation, suggesting a rather narrow range in
which subitizing-like categorization processes blend into greater reliance on
adaptable magnitude information.
PMID- 29342638
TI - The contribution of fish studies to the "number sense" debate.
AB - Leibovich et al. propose that number sense is not innate but gradually emergent
during ontogeny following experience. We argue that this hypothesis cannot be
reasonably tested in humans, in which the contribution of neural maturation and
experience cannot be experimentally manipulated. Studies on animals, especially
fish, can more effectively provide critical insights into the innate nature of
numerical abilities.
PMID- 29342639
TI - Number faculty is alive and kicking: On number discriminations and number
neurons.
AB - Leibovich et al. advocate for a single "sense of magnitude" to which a dedicated
faculty for number could allegedly be reduced. This conclusion is unjustified as
the authors adopt an unnecessarily narrow definition of "number sense," neglect
studies that demonstrate non-symbolic numerosity representation, and furthermore
ignore abstract number representations in the brain.
PMID- 29342640
TI - Innateness of magnitude perception? Skill can be acquired and mastered at all
ages.
AB - We agree with Leibovich et al.'s argument that the number sense theory should be
re-evaluated. However, we argue that highly efficient skills (i.e., fluent and
highly accurate, "automatic," performance) can be acquired and mastered at all
ages. Hence, evidence for primacy or fluency in perceiving continuous magnitudes
is insufficient for supporting strong conclusions about the innateness of this
aptitude.
PMID- 29342641
TI - Magnitude rather than number: More evidence needed.
AB - Leibovich et al. do not present enough empirical support to overturn decades of
work supporting a number sense nor to convince the reader that a magnitude sense
provides a better explanation of the literature. Here we highlight what we feel
are the main points of weakness and the types of evidence that could be provided
to be more convincing.
PMID- 29342642
TI - Is the ANS linked to mathematics performance?
AB - Leibovich et al. argue persuasively that researchers should not assume that
approximate number system (ANS) tasks harness an innate sense of number. However,
some studies have reported a causal link between ANS tasks and mathematics
performance, implicating the ANS in the development of numerical skills. Here we
report a p-curve analysis, which indicates that these experimental studies do not
contain evidential value.
PMID- 29342643
TI - Infants, animals, and the origins of number.
AB - Where do human numerical abilities come from? Leibovich et al. argue against
nativist views of numerical development noting limitations in newborns' vision
and limitations regarding newborns' ability to individuate objects. I argue that
these considerations do not undermine competing nativist views and that Leibovich
et al.'s model itself presupposes that infant learners have numerical
representations.
PMID- 29342644
TI - What is the precise role of cognitive control in the development of a sense of
number?
AB - The theory put forward by Leibovich et al. of how children acquire a sense of
number does not specify the mechanisms through which cognitive control plays a
role in this process. We argue that visual attention and number word knowledge
influence each other over development and contribute to the development of the
concept of number.
PMID- 29342645
TI - What is a number? The interplay between number and continuous magnitudes.
AB - Leibovich et al. argue that it is impossible to control for all continuous
magnitudes in a numerical task. We contend that continuous magnitudes (i.e.,
perimeter, area, density) can be simultaneously controlled. Furthermore, we argue
that shedding light on the interplay between number and continuous magnitudes -
rather than considering them independently - will provide a much more fruitful
approach to understanding mathematical abilities.
PMID- 29342646
TI - The evolvement of discrete representations from continuous stimulus properties: A
possible overarching principle of cognition.
AB - Leibovich et al. propose that non-symbolic numerosity abilities develop from the
processing of more basic, continuous magnitudes such as size, area, and density.
Here I review similar arguments arising in the visual perception field and
further propose that the evolvement of discrete representations from continuous
stimulus properties may be a fundamental characteristic of cognitive development.
PMID- 29342647
TI - Controlling for continuous variables is not futile: What we can learn about
number representation despite imperfect control.
AB - Leibovich et al. argue that because it is impossible to isolate numerosity in a
stimulus set, attempts to show that number is processed independently of
continuous magnitudes are necessarily in vain. I propose that through clever
design and manipulation of confounding variables, we can gain deep insight into
number representation and its relationship to the representation of other
magnitudes.
PMID- 29342648
TI - Toward an integrative approach to numerical cognition.
AB - In response to the commentaries, we have refined our suggested model and
discussed ways in which the model could be further expanded. In this context, we
have elaborated on the role of specific continuous magnitudes. We have also found
it important to devote a section to evidence considered the "smoking gun" of the
approximate number system theory, including cross-modal studies, animal studies,
and so forth. Lastly, we suggested some ways in which the scientific community
can promote more transparent and collaborative research by using an open science
approach, sharing both raw data and stimuli. We thank the contributors for their
enlightening comments and look forward to future developments in the field.
PMID- 29342649
TI - Approximate number sense theory or approximate theory of magnitude?
AB - Leibovich et al. argue that the evidence in favor of a perceptual mechanism
devoted to the extraction of numerosity from visual collections is unsatisfactory
and propose to replace it with an unspecific mechanism capturing approximate
magnitudes from continuous dimensions. We argue that their representation of the
evidence is incomplete and that their theoretical proposal is too vague to be
useful.
PMID- 29342650
TI - Computational foundations of the visual number sense.
AB - We provide an emergentist perspective on the computational mechanism underlying
numerosity perception, its development, and the role of inhibition, based on our
deep neural network model. We argue that the influence of continuous visual
properties does not challenge the notion of number sense, but reveals limit
conditions for the computation that yields invariance in numerosity perception.
Alternative accounts should be formalized in a computational model.
PMID- 29342651
TI - The number sense is neither last resort nor of primary import.
AB - Leibovich et al. argue that evidence for an innate sense of number in children
and animals may instead reflect the processing of continuous magnitude
properties. However, some comparative research highlights responding on the basis
of numerosity when non-numerical confounds are controlled. Future comparative
tests might evaluate how early experience with continuous magnitudes affects the
development of a sense of number.
PMID- 29342652
TI - Perceiving numerosity from birth.
AB - Leibovich et al. opened up an important discussion on the nature and origins of
numerosity perception. The authors rightly point out that non-numerical features
of stimuli influence this ability. Despite these biases, there is evidence that
from birth, humans perceive and represent numerosities, and not just non
numerical quantitative features such as item size, density, and convex hull.
PMID- 29342653
TI - From continuous magnitudes to symbolic numbers: The centrality of ratio.
AB - Leibovich et al.'s theory neither accounts for the deep connections between whole
numbers and other classes of number nor provides a potential mechanism for
mapping continuous magnitudes to symbolic numbers. We argue that focusing on non
symbolic ratio processing abilities can furnish a more expansive account of
numerical cognition that remedies these shortcomings.
PMID- 29342654
TI - Negative results are needed to show the specific value of a cultural explanation
for g.
AB - Burkart et al. suggest that social learning can explain the cognitive positive
manifold for social animals, including humans. We caution that simpler
explanations of positive trait intercorrelations exist, such as genetic load. To
test the suggested explanation's specificity, we also need to examine non-social
species and traits, such as health, that are distal to cognitive abilities.
PMID- 29342655
TI - Domains of generality.
AB - We argue that general intelligence, as presented in the target article, generates
multiple distinct and non-equivalent characterisations. Clarifying this central
concept is necessary for assessing Burkart et al.'s proposal that the cultural
intelligence hypothesis is the best explanation for the evolution of general
intelligence. We assess this claim by considering two characterisations of
general intelligence presented in the article.
PMID- 29342656
TI - Theory of mind: A foundational component of human general intelligence.
AB - To understand the evolution of general intelligence, Burkart et al. endorse a
"cultural intelligence approach," which emphasizes the critical importance of
social interaction. We argue that theory of mind provides an essential foundation
and shared perspective for the efficient ontogenetic transmission of crucial
knowledge and skills during human development and, together with language, can
account for superior human general intelligence.
PMID- 29342657
TI - Coexistence of general intelligence and specialized modules.
AB - Here, we specifically discuss why and to what extent we agree with Burkart et al.
about the coexistence of general intelligence and modular cognitive adaptations,
and why we believe that the distinction between primary and secondary modules
they propose is indeed essential.
PMID- 29342658
TI - G but not g: In search of the evolutionary continuity of intelligence.
AB - Conceptualizing intelligence in its biological context, as the expression of
manifold adaptations, compels a rethinking of measuring this characteristic in
humans, relying also on animal studies of analogous skills. Mental manipulation,
as an extension of object manipulation, provides a continuous, biologically based
concept for studying G as it pertains to individual differences in humans and
other species.
PMID- 29342659
TI - Taking a multiple intelligences (MI) perspective.
AB - The theory of multiple intelligences (MI) seeks to describe and encompass the
range of human cognitive capacities. In challenging the concept of general
intelligence, we can apply an MI perspective that may provide a more useful
approach to cognitive differences within and across species.
PMID- 29342660
TI - The evolution of general intelligence in all animals and machines.
AB - We strongly agree that general intelligence occurs in many animals but find the
cultural intelligence hypothesis of limited usefulness. Any viable hypothesis
explaining the evolution of general intelligence should be able to account for it
in all species where it is known to occur, and should also predict the conditions
under which we can develop machines with general intelligence as well.
PMID- 29342661
TI - The false dichotomy of domain-specific versus domain-general cognition.
AB - The qualitative division between domain-general and domain-specific cognition is
unsubstantiated. The distinction is instead better viewed as opposites on a
gradual scale, which has more explanatory power and fits current empirical
evidence better. We also argue that causal cognition may be more general than
social learning, which it often involves.
PMID- 29342662
TI - Contemporary evolutionary psychology and the evolution of intelligence.
AB - Burkart et al.'s impressive synthesis will serve as a valuable resource for
intelligence research. Despite its strengths, the target article falls short of
offering compelling explanations for the evolution of intelligence. Here, we
outline its shortcomings, illustrate how these can lead to misguided conclusions
about the evolution of intelligence, and suggest ways to address the article's
key questions.
PMID- 29342663
TI - Understanding the relationship between general intelligence and socio-cognitive
abilities in humans.
AB - Burkart et al. consider that the relationship between general intelligence and
socio-cognitive abilities is poorly understood in animals and humans. We examine
this conclusion in the perspective of an already substantial evidence base on the
relationship among general intelligence, theory of mind, and emotional
intelligence. We propose a link between general intelligence and socio-cognitive
abilities within humans.
PMID- 29342664
TI - Of mice and men, nature and nurture, and a few red herrings.
AB - Burkart et al.'s proposal is based on three false premises: (1) theories of the
mind are either domain-specific/modular (DSM) or domain-general (DG); (2) DSM
systems are considered inflexible, built by nature; and (3) animal minds are
deemed as purely DSM. Clearing up these conceptual confusions is a necessary
first step in understanding how general intelligence evolved.
PMID- 29342665
TI - Where is the evidence for general intelligence in nonhuman animals?
AB - This commentary contrasts evolutionary plausibility with empirical evidence and
cognitive continuity with radiation and convergent evolution. So far, neither
within-species nor between-species comparisons on the basis of rigorous
experimental and species-appropriate tests substantiate the claims made in the
target article. Caution is advisable on meta-analytical comparisons that
primarily rely on publication frequencies and overgeneralizations (from murids
and primates to other nonhuman animals).
PMID- 29342666
TI - The evolution of fluid intelligence meets formative g.
AB - The argument by Burkart et al. in the target article relates to fluid (not
general) intelligence: a domain-general ability involved in complex, novel
problem solving, and strongly related to working memory and executive functions.
A formative framework, under which the general factor of intelligence is the
common consequence, not the common cause of the covariance among tests is more in
line with an evolutionary approach.
PMID- 29342667
TI - Hierarchy, multidomain modules, and the evolution of intelligence.
AB - In this commentary, we support a complex, mosaic, and multimodal approach to the
evolution of intelligence. Using the arcuate fasciculus as an example of
discontinuity in the evolution of neurobiological architectures, we argue that
the strict dichotomy of modules versus G, adopted by Burkart et al. in the target
article, is insufficient to interpret the available statistical and experimental
evidence.
PMID- 29342668
TI - Habit formation generates secondary modules that emulate the efficiency of
evolved behavior.
AB - We discuss the evolutionary implications of connections drawn between the
authors' learned "secondary modules" and the habit-formation system that appears
to be ubiquitous among vertebrates. Prior to any subsequent coevolution with
social learning, we suggest that aspects of general intelligence likely arose in
tandem with mechanisms of adaptive motor control that rely on basal ganglia
circuitry.
PMID- 29342669
TI - "Birdbrains" should not be ignored in studying the evolution of g.
AB - The authors evaluate evidence for general intelligence (g) in nonhumans but lean
heavily toward mammalian data. They mention, but do not discuss in detail,
evidence for g in nonmammalian species, for which substantive material exists. I
refer to a number of avian studies, particularly in corvids and parrots, which
would add breadth to the material presented in the target article.
PMID- 29342670
TI - Evolution, brain size, and variations in intelligence.
AB - Across taxonomic subfamilies, variations in intelligence (G) are sometimes
related to brain size. However, within species, brain size plays a smaller role
in explaining variations in general intelligence (g), and the cause-and-effect
relationship may be opposite to what appears intuitive. Instead, individual
differences in intelligence may reflect variations in domain-general processes
that are only superficially related to brain size.
PMID- 29342671
TI - The evolution of analytic thought?
AB - We argue that the truly unique aspect of human intelligence is not the variety of
cognitive skills that are ontogenetically constructed, but rather the capacity to
decide when to develop and apply said skills. Even if there is good evidence for
g in nonhuman animals, we are left with major questions about how the disposition
to think analytically can evolve.
PMID- 29342672
TI - General intelligence is an emerging property, not an evolutionary puzzle.
AB - Burkart et al. contend that general intelligence poses a major evolutionary
puzzle. This assertion presupposes a reification of general intelligence - that
is, assuming that it is one "thing" that must have been selected as such.
However, viewing general intelligence as an emerging property of multiple
cognitive abilities (each with their own selective advantage) requires no
additional evolutionary explanation.
PMID- 29342673
TI - General intelligence does not help us understand cognitive evolution.
AB - Burkart et al. conflate the domain-specificity of cognitive processes with the
statistical pattern of variance in behavioural measures that partly reflect those
processes. General intelligence is a statistical abstraction, not a cognitive
trait, and we argue that the former does not warrant inferences about the nature
or evolution of the latter.
PMID- 29342674
TI - When does cultural transmission favour or instead substitute for general
intelligence?
AB - The cultural intelligence hypothesis is an exciting new development. The
hypothesis that it encourages general intelligence is intriguing, but it presents
a paradox insofar as social learning is often suggested to instead reduce
reliance on individual cognition and exploration. There is thus a need to specify
more clearly the contexts in which cultural transmission may select for general
intelligence.
PMID- 29342675
TI - An all-positive correlation matrix is not evidence of domain-general
intelligence.
AB - We welcome the cross-disciplinary approach taken by Burkart et al. to probe the
evolution of intelligence. We note several concerns: the uses of g and G, rank
ordering species on cognitive ability, and the meaning of general intelligence.
This subject demands insights from several fields, and we look forward to cross
disciplinary collaborations.
PMID- 29342676
TI - Disentangling learning from knowing: Does associative learning ability underlie
performances on cognitive test batteries?
AB - Are the mechanisms underlying variations in the performance of animals on
cognitive test batteries analogous to those of humans? Differences might result
from procedural inconsistencies in test battery design, but also from differences
in how animals and humans solve cognitive problems. We suggest differentiating
associative-based (learning) from rule-based (knowing) tasks to further our
understanding of cognitive evolution across species.
PMID- 29342677
TI - General intelligence is a source of individual differences between species:
Solving an anomaly.
AB - Burkart et al. present a paradox - general factors of intelligence exist among
individual differences (g) in performance in several species, and also at the
aggregate level (G); however, there is ambiguous evidence for the existence of g
when analyzing data using a mixed approach, that is, when comparing individuals
of different species using the same cognitive ability battery. Here, we present
an empirical solution to this paradox.
PMID- 29342678
TI - Genomic data can illuminate the architecture and evolution of cognitive
abilities.
AB - Does general intelligence exist across species, and has it been a target of
natural selection? These questions can be addressed with genomic data, which can
rule out artifacts by demonstrating that distinct cognitive abilities are
genetically correlated and thus share a biological substrate. This work has begun
with data from humans and can be extended to other species; it should focus not
only on general intelligence but also specific capacities like language and
spatial ability.
PMID- 29342679
TI - Future directions for studying the evolution of general intelligence.
AB - The goal of our target article was to lay out current evidence relevant to the
question of whether general intelligence can be found in nonhuman animals in
order to better understand its evolution in humans. The topic is a controversial
one, as evident from the broad range of partly incompatible comments it has
elicited. The main goal of our response is to translate these issues into
testable empirical predictions, which together can provide the basis for a broad
research agenda.
PMID- 29342680
TI - G and g: Two markers of a general cognitive ability, or none?
AB - The search for general processes that underlie intelligence in nonhumans has
followed two strategies: one that concerns observing differences between nonhuman
species (G), the second that concerns observing individual differences within a
nonhuman species (g). This commentary takes issue with both attempts to mark a
general factor: Differential responding to contextual variables compromises the
search for G, and the lack of predictive validity compromises g.
PMID- 29342681
TI - A pointer's hypothesis of general intelligence evolved from domain-specific
demands.
AB - A higher-order function may evolve phylogenetically if it is demanded by multiple
domain-specific modules. Task-specificity to solve a unique adaptive problem
(e.g., foraging or mating) should be distinguished from function-specificity to
deal with a common computational demand (e.g., numeracy, verbal communication)
required by many tasks. A localized brain function is likely a result of such
common computational demand.
PMID- 29342682
TI - It's time to move beyond the "Great Chain of Being".
AB - The target article provides an anthropocentric model of understanding
intelligence in nonhuman animals. Such an idea dates back to Plato and, more
recently, Lovejoy: On Earth, humans are at the top and other animals at
successively lower levels. We then evaluate these other animals by our
anthropocentric folk theories of their intelligence rather than by their own
adaptive requirements.
PMID- 29342683
TI - Theories or fragments?
AB - Lake et al. argue persuasively that modelling human-like intelligence requires
flexible, compositional representations in order to embody world knowledge. But
human knowledge is too sparse and self-contradictory to be embedded in "intuitive
theories." We argue, instead, that knowledge is grounded in exemplar-based
learning and generalization, combined with high flexible generalization, a
viewpoint compatible both with non-parametric Bayesian modelling and with sub
symbolic methods such as neural networks.
PMID- 29342684
TI - The architecture challenge: Future artificial-intelligence systems will require
sophisticated architectures, and knowledge of the brain might guide their
construction.
AB - In this commentary, we highlight a crucial challenge posed by the proposal of
Lake et al. to introduce key elements of human cognition into deep neural
networks and future artificial-intelligence systems: the need to design effective
sophisticated architectures. We propose that looking at the brain is an important
means of facing this great challenge.
PMID- 29342685
TI - Building machines that learn and think for themselves.
AB - We agree with Lake and colleagues on their list of "key ingredients" for building
human-like intelligence, including the idea that model-based reasoning is
essential. However, we favor an approach that centers on one additional
ingredient: autonomy. In particular, we aim toward agents that can both build and
exploit their own internal models, with minimal human hand engineering. We
believe an approach centered on autonomous learning has the greatest chance of
success as we scale toward real-world complexity, tackling domains for which
ready-made formal models are not available. Here, we survey several important
examples of the progress that has been made toward building autonomous agents
with human-like abilities, and highlight some outstanding challenges.
PMID- 29342686
TI - Back to the future: The return of cognitive functionalism.
AB - The claims that learning systems must build causal models and provide
explanations of their inferences are not new, and advocate a cognitive
functionalism for artificial intelligence. This view conflates the relationships
between implicit and explicit knowledge representation. We present recent
evidence that neural networks do engage in model building, which is implicit, and
cannot be dissociated from the learning process.
PMID- 29342687
TI - Deep-learning networks and the functional architecture of executive control.
AB - Lake et al. underrate both the promise and the limitations of contemporary deep
learning techniques. The promise lies in combining those techniques with broad
multisensory training as experienced by infants and children. The limitations lie
in the need for such systems to possess functional subsystems that generate,
monitor, and switch goals and strategies in the absence of human intervention.
PMID- 29342688
TI - Children begin with the same start-up software, but their software updates are
cultural.
AB - We propose that early in ontogeny, children's core cognitive abilities are shaped
by culturally dependent "software updates." The role of sociocultural inputs in
the development of children's learning is largely missing from Lake et al.'s
discussion of the development of human-like artificial intelligence, but its
inclusion would help move research even closer to machines that can learn and
think like humans.
PMID- 29342689
TI - Causal generative models are just a start.
AB - Human reasoning is richer than Lake et al. acknowledge, and the emphasis on
theories of how images and scenes are synthesized is misleading. For example, the
world knowledge used in vision presumably involves a combination of geometric,
physical, and other knowledge, rather than just a causal theory of how the image
was produced. In physical reasoning, a model can be a set of constraints rather
than a physics engine. In intuitive psychology, many inferences proceed without
detailed causal generative models. How humans reliably perform such inferences,
often in the face of radically incomplete information, remains a mystery.
PMID- 29342690
TI - What can the brain teach us about building artificial intelligence?
AB - Lake et al. offer a timely critique on the recent accomplishments in artificial
intelligence from the vantage point of human intelligence and provide insightful
suggestions about research directions for building more human-like intelligence.
Because we agree with most of the points they raised, here we offer a few points
that are complementary.
PMID- 29342691
TI - Thinking like animals or thinking like colleagues?
AB - We comment on ways in which Lake et al. advance our understanding of the
machinery of intelligence and offer suggestions. The first set concerns animal
level versus human-level intelligence. The second concerns the urgent need to
address ethical issues when evaluating the state of artificial intelligence.
PMID- 29342692
TI - Evidence from machines that learn and think like people.
AB - We agree with Lake et al.'s trenchant analysis of deep learning systems,
including that they are highly brittle and that they need vastly more examples
than do people. We also agree that human cognition relies heavily on structured
relational representations. However, we differ in our analysis of human cognitive
processing. We argue that (1) analogical comparison processes are central to
human cognition; and (2) intuitive physical knowledge is captured by qualitative
representations, rather than quantitative simulations.
PMID- 29342693
TI - Understand the cogs to understand cognition.
AB - Lake et al. suggest that current AI systems lack the inductive biases that enable
human learning. However, Lake et al.'s proposed biases may not directly map onto
mechanisms in the developing brain. A convergence of fields may soon create a
correspondence between biological neural circuits and optimization in structured
architectures, allowing us to systematically dissect how brains learn.
PMID- 29342694
TI - Crossmodal lifelong learning in hybrid neural embodied architectures.
AB - Lake et al. point out that grounding learning in general principles of embodied
perception and social cognition is the next step in advancing artificial
intelligent machines. We suggest it is necessary to go further and consider
lifelong learning, which includes developmental learning, focused on embodiment
as applied in developmental robotics and neurorobotics, and crossmodal learning
that facilitates integrating multiple senses.
PMID- 29342695
TI - Social-motor experience and perception-action learning bring efficiency to
machines.
AB - Lake et al. proposed a way to build machines that learn as fast as people do.
This can be possible only if machines follow the human processes: the perception
action loop. People perceive and act to understand new objects or to promote
specific behavior to their partners. In return, the object/person provides
information that induces another reaction, and so on.
PMID- 29342696
TI - Autonomous development and learning in artificial intelligence and robotics:
Scaling up deep learning to human-like learning.
AB - Autonomous lifelong development and learning are fundamental capabilities of
humans, differentiating them from current deep learning systems. However, other
branches of artificial intelligence have designed crucial ingredients towards
autonomous learning: curiosity and intrinsic motivation, social learning and
natural interaction with peers, and embodiment. These mechanisms guide
exploration and autonomous choice of goals, and integrating them with deep
learning opens stimulating perspectives.
PMID- 29342697
TI - The fork in the road.
AB - Machines that learn and think like people should simulate how people really think
in their everyday lives. The field of artificial intelligence originally traveled
down two roads, one of which emphasized abstract, idealized, rational thinking
and the other, which emphasized the emotionally charged and motivationally
complex situations in which people often find themselves. The roads should have
converged but never did. That's too bad.
PMID- 29342698
TI - Avoiding frostbite: It helps to learn from others.
AB - Machines that learn and think like people must be able to learn from others.
Social learning speeds up the learning process and - in combination with language
- is a gateway to abstract and unobservable information. Social learning also
facilitates the accumulation of knowledge across generations, helping people and
artificial intelligences learn things that no individual could learn in a
lifetime.
PMID- 29342699
TI - Digging deeper on "deep" learning: A computational ecology approach.
AB - We propose an alternative approach to "deep" learning that is based on
computational ecologies of structurally diverse artificial neural networks, and
on dynamic associative memory responses to stimuli. Rather than focusing on
massive computation of many different examples of a single situation, we opt for
model-based learning and adaptive flexibility. Cross-fertilization of learning
processes across multiple domains is the fundamental feature of human
intelligence that must inform "new" artificial intelligence.
PMID- 29342700
TI - Building brains that communicate like machines.
AB - Reverse engineering human cognitive processes may improve artificial
intelligence, but this approach implies we have little to learn regarding brains
from human-engineered systems. On the contrary, engineered technologies of
dynamic network communication have many features that highlight analogous, poorly
understood, or ignored aspects of brain and cognitive function, and mechanisms
fundamental to these technologies can be usefully investigated in brains.
PMID- 29342701
TI - Building on prior knowledge without building it in.
AB - Lake et al. propose that people rely on "start-up software," "causal models," and
"intuitive theories" built using compositional representations to learn new tasks
more efficiently than some deep neural network models. We highlight the many
drawbacks of a commitment to compositional representations and describe our
continuing effort to explore how the ability to build on prior knowledge and to
learn new tasks efficiently could arise through learning in deep neural networks.
PMID- 29342702
TI - Will human-like machines make human-like mistakes?
AB - Although we agree with Lake et al.'s central argument, there are numerous flaws
in the way people use causal models. Our models are often incorrect, resistant to
correction, and applied inappropriately to new situations. These deficiencies are
pervasive and have real-world consequences. Developers of machines with similar
capacities should proceed with caution.
PMID- 29342703
TI - The humanness of artificial non-normative personalities.
AB - Technoscientific ambitions for perfecting human-like machines, by advancing state
of-the-art neuromorphic architectures and cognitive computing, may end in ironic
regret without pondering the humanness of fallible artificial non-normative
personalities. Self-organizing artificial personalities individualize machine
performance and identity through fuzzy conscientiousness, emotionality,
extraversion/introversion, and other traits, rendering insights into technology
assisted human evolution, robot ethology/pedagogy, and best practices against
unwanted autonomous machine behavior.
PMID- 29342704
TI - The importance of motivation and emotion for explaining human cognition.
AB - Lake et al. discuss building blocks of human intelligence that are quite
different from those of artificial intelligence. We argue that a theory of human
intelligence has to incorporate human motivations and emotions. The interaction
of motivation, emotion, and cognition is the real strength of human intelligence
and distinguishes it from artificial intelligence.
PMID- 29342705
TI - Building machines that adapt and compute like brains.
AB - Building machines that learn and think like humans is essential not only for
cognitive science, but also for computational neuroscience, whose ultimate goal
is to understand how cognition is implemented in biological brains. A new
cognitive computational neuroscience should build cognitive-level and neural
level models, understand their relationships, and test both types of models with
both brain and behavioral data.
PMID- 29342706
TI - Benefits of embodiment.
AB - Physical competence is acquired through animals' embodied interaction with their
physical environments, and psychological competence is acquired through situated
interaction with other agents. The acquired neural models essential to these
competencies are implicit and permit more fluent and nuanced behavior than
explicit models. The challenge is to understand how such models are acquired and
used to control behavior.
PMID- 29342707
TI - Human-like machines: Transparency and comprehensibility.
AB - Artificial intelligence algorithms seek inspiration from human cognitive systems
in areas where humans outperform machines. But on what level should algorithms
try to approximate human cognition? We argue that human-like machines should be
designed to make decisions in transparent and comprehensible ways, which can be
achieved by accurately mirroring human cognitive processes.
PMID- 29342708
TI - Ingredients of intelligence: From classic debates to an engineering roadmap.
AB - We were encouraged by the broad enthusiasm for building machines that learn and
think in more human-like ways. Many commentators saw our set of key ingredients
as helpful, but there was disagreement regarding the origin and structure of
those ingredients. Our response covers three main dimensions of this
disagreement: nature versus nurture, coherent theories versus theory fragments,
and symbolic versus sub-symbolic representations. These dimensions align with
classic debates in artificial intelligence and cognitive science, although,
rather than embracing these debates, we emphasize ways of moving beyond them.
Several commentators saw our set of key ingredients as incomplete and offered a
wide range of additions. We agree that these additional ingredients are important
in the long run and discuss prospects for incorporating them. Finally, we
consider some of the ethical questions raised regarding the research program as a
whole.
PMID- 29342709
TI - The argument for single-purpose robots.
AB - The argument by Lake et al. to create more human-like robots is, first,
implausible and, second, undesirable. It seems implausible to me that a robot
might have friends, fall in love, read Foucault, prefer Scotch to Bourbon, and so
on. It seems undesirable because we already have 7 billion people on earth and
don't really need more.
PMID- 29342710
TI - Intelligent machines and human minds.
AB - The search for a deep, multileveled understanding of human intelligence is
perhaps the grand challenge for 21st-century science, with broad implications for
technology. The project of building machines that think like humans is central to
meeting this challenge and critical to efforts to craft new technologies for
human benefit.
PMID- 29342711
TI - Horses for courses: When acceptability judgments are more suitable than
structural priming (and vice versa).
AB - Although structural priming is often the most suitable paradigm, it sometimes
misses effects that are detected by more sensitive acceptability-judgment tasks,
thus yielding incorrect conclusions. For example, Branigan & Pickering's (B&P's)
claim that "syntactic representations do not contain semantic information" (sect.
2.1, para. 2), while supported by structural-priming studies of the passive, is
undermined by an acceptability-judgment study of this construction.
PMID- 29342712
TI - Microscopic and macroscopic approaches to the mental representations of second
languages.
AB - With a particular reference to second language (L2), we discuss (1) how
structural priming can be used to tap into L2 representations and their
relationships with first and target language representations; and (2) how complex
networks additionally can be used to reveal the global and local patterning of L2
linguistic features and L2 developmental trajectories.
PMID- 29342713
TI - Structural priming can inform syntactic analyses of partially grammaticalized
constructions.
AB - Branigan & Pickering (B&P) argue successfully that structural priming provides
valuable information for developing psychologically plausible syntactic and
semantic theories. I discuss how their approach can be used to help determine
whether partially grammaticalized constructions that have undergone semantic
change also have undergone syntactic reanalysis. I then consider cases in which
evidence from priming cannot distinguish between competing syntactic analyses.
PMID- 29342714
TI - The limitations of structural priming are not the limits of linguistic theory.
AB - Structural priming is a useful technique for testing the predictions of
linguistic theories, but one cannot conclude anything definitively about the
shape of those theories from any particular methodology.
PMID- 29342715
TI - Don't shoot the giant whose shoulders we are standing on.
AB - Structural priming is a sufficient but not a necessary condition for proving the
existence of representations. Absence of evidence is not evidence of absence.
Cognitive science relies on the legitimacy of positing representations and
processes without "proving" every component. Also, psycholinguistics relies on
other methods, including acceptability judgments, to find the materials for
priming experiments in the first place.
PMID- 29342716
TI - If priming is graded rather than all-or-none, can reactivating abstract
structures be the underlying mechanism?
AB - In our commentary on Branigan & Pickering (B&P), we start by arguing that the
authors implicitly adopt several assumptions, the consequence of which is to make
further claims necessary and/or sufficient. Crucially, the authors assume the
existence of discrete units at various levels of linguistic granularity that then
must be operated upon by combinatorial mechanisms and rules (i.e.,
decomposition/recomposition). They further argue that structural priming provides
a powerful tool to study abstract, structural representations. We provide
evidence that priming effects in production are characterized better as graded
than as all-or-none and that priming need not arise from a mechanism that
(re)activates a shared but abstract internal structure.
PMID- 29342717
TI - A usage-based cognitive linguistic (re-)interpretation of priming evidence.
AB - Usage-based cognitive linguistic (UBCL) theories offer a unifying interpretation
of the different (structural vs. [more] lexical) priming effects reported by
Branigan & Pickering (B&P), and they provide an ideal basis for explaining
contextual influences on priming. However, they also call into question B&P's
claim that priming "provides evidence that is directly informative about mental
representation" (sect. 1.5, para. 1).
PMID- 29342718
TI - The logic of syntactic priming and acceptability judgments.
AB - A critical flaw in Branigan & Pickering's (B&P's) advocacy of structural priming
is the absence of a theory of priming. This undermines their claims about the
value of priming as a methodology. In contrast, acceptability judgments enable
clearer inferences about structure. It is important to engage thoroughly with the
logic behind different structural diagnostics.
PMID- 29342719
TI - Converging on a theory of language through multiple methods.
AB - Assuming that linguistic representation has been studied only by linguists using
grammaticality judgments, Branigan & Pickering (B&P) present structural priming
as a novel alternative. We show that their assumptions are incorrect for
cognitive-functional linguistics, exposing converging perspectives on
form/meaning pairings between generativists and cognitive-functional linguists
that we hope will spark the cross-disciplinary discussion necessary to produce a
cognitively plausible model of linguistic representation.
PMID- 29342720
TI - Don't forget the neurobiology: An experimental approach to linguistic
representation.
AB - Acceptability judgments are no longer acceptable as the holy grail for testing
the nature of linguistic representations. Experimental and quantitative methods
should be used to test theoretical claims in psycholinguistics. These methods
should include not only behavior, but also the more recent possibilities to probe
the neural codes for language-relevant representations.
PMID- 29342721
TI - Acceptability judgments still matter: Deafness and documentation.
AB - The target article's call to end reliance on acceptability judgments is
premature. First, it restricts syntactic inquiry to cases were a semantically
equivalent alternative is available. Second, priming studies require groups of
participants who are linguistically homogenous and whose grammar is known to the
researcher. These requirements would eliminate two major research areas:
syntactic competence in d/Deaf individuals, and language documentation. (We
follow the convention of using deaf to describe hearing levels, Deaf to describe
cultural identity, and d/Deaf to include both. Our own work has focused on Deaf
signers, but the same concerns could apply to other deaf populations.).
PMID- 29342722
TI - Syntactic levels, lexicalism, and ellipsis: The jury is still out.
AB - Structural priming data are sometimes compatible with several theoretical views,
as shown here for three key theoretical claims. One reason is that prime
sentences affect multiple representational levels driving syntactic choice.
Additionally, priming is affected by further cognitive functions (e.g., memory).
We therefore see priming as a useful tool for the investigation of linguistic
representation but not the only tool.
PMID- 29342723
TI - Structural priming supports grammatical networks.
AB - As Branigan & Pickering (B&P) argue, structural priming has important
implications for the theory of language structure, but these implications go
beyond those suggested. Priming implies a network structure, so the grammar must
be a network and so must sentence structure. Instead of phrase structure, the
most promising model for syntactic structure is enriched dependency structure, as
in Word Grammar.
PMID- 29342724
TI - Action sequences instead of representational levels.
AB - Despite enthusiastic agreement that experimental data are directly relevant for
determining grammar architecture, we present one main objection to the
conclusions that the authors draw from their results: The data are perfectly
compatible - in fact, much more in line - with an alternative that does not rely
on syntactic representations. Instead, it is processing actions whose activation
for comprehension/production explains intra-/inter-speaker priming.
PMID- 29342725
TI - What structural priming can and cannot reveal.
AB - The nature of mental representations of linguistic expressions in relation to the
time course from intention to articulation is a major issue. We discuss Branigan
& Pickering's (B&P's) proposal to use structural priming to tap into this
process. We show that their interpretation of their findings cannot be
maintained. We reinterpret these results and suggest a revision of their
conclusions.
PMID- 29342726
TI - On the nature of structure in structural priming.
AB - Like Branigan & Pickering (B&P), we agree that processing evidence is important
for linguistic theorization; however, without much evidence of priming of
hierarchical argument structure independent of linear ordering, the nature of
"structure" in structural priming remains unclear. Consequently, it is an
empirical question whether structural priming and acceptability judgments tap
into cognitive processes of a similar nature.
PMID- 29342727
TI - Structural priming, action planning, and grammar.
AB - Structural priming is poorly understood and cannot inform accounts of grammar for
two reasons. First, those who view performance as grammar + processing will
always be able to attribute psycholinguistic data to processing rather than
grammar. Second, structural priming may be simply an example of hysteresis
effects in general action planning. If so, then priming offers no special insight
into grammar.
PMID- 29342728
TI - Moving beyond the priming of single-language sentences: A proposal for a
comprehensive model to account for linguistic representation in bilinguals.
AB - In their target article, Branigan & Pickering (B&P) briefly discuss bilingual
language representation, focusing primarily on cross-language priming between
single-language sentences. We follow up on this discussion by showing how
structural priming drives real-life phenomena of bilingual language use beyond
the priming of unilingual sentences and by arguing that B&P's account should be
extended with a representation for language membership.
PMID- 29342729
TI - Considering experimental and observational evidence of priming together, syntax
doesn't look so autonomous.
AB - We agree with Branigan & Pickering (B&P) that structural priming experiments
should supplant grammaticality judgments for testing linguistic representation.
However, B&P overlook a vast (corpus-)linguistic literature that converges with -
but extends - the experimental findings. B&P conclude that syntax is functionally
independent of the lexicon. We argue that a broader approach to priming reveals
cracks in the facade of syntactic autonomy.
PMID- 29342730
TI - Structural priming is most useful when the conclusions are statistically robust.
AB - Branigan & Pickering (B&P) claim that the success of structural priming as a
method should "end the current reliance on acceptability judgments." Structural
priming is an interesting and useful phenomenon, but we are dubious that the
effect is powerful enough to test many detailed claims about specific points of
syntactic theory.
PMID- 29342731
TI - Priming methods in semantics and pragmatics.
AB - Structural priming is a powerful method to inform linguistic theories. We argue
that this method extends nicely beyond syntax to theories of meaning. Priming,
however, should still be seen as only one of the tools available for linguistic
data collection. Specifically, because priming can occur at different,
potentially conflicting levels, it cannot detect every aspect of linguistic
representations.
PMID- 29342732
TI - Can structural priming answer the important questions about language?
AB - Structural priming makes a valuable contribution to psycholinguistics, but it
taps into implicit memory representations and processes that may differ from what
is deployed during online language processing. As a result, the strength of
inductive inference regarding linguistic representation is rather limited. We
question whether implicit memory for language can and should be equated with
linguistic representation or with language processing.
PMID- 29342733
TI - The syntax of priming.
AB - Priming reflects the reactivation of processing routines that map strings of
words onto semantic representations (and vice versa) without the mediation of
syntactic structure, including the "flat structure" that Branigan & Pickering
(B&P) propose. Key evidence for this claim comes from the possibility of priming
relations involving subject-verb sequences, which are not syntactic constituents.
PMID- 29342734
TI - Structural priming is not a Royal Road to representations.
AB - Branigan & Pickering (B&P) propose that the structural priming paradigm is a
Royal Road to linguistic representations of any kind, unobstructed by influences
of psychological processes. In my view, however, they are too optimistic about
the versatility of the paradigm and, more importantly, its ability to provide
direct evidence about the nature of stored linguistic representations.
PMID- 29342735
TI - Structural priming is a useful but imperfect technique for studying all
linguistic representations, including those of pragmatics.
AB - Structural priming is a useful tool for investigating linguistics
representations. We argue that structural priming can be extended to the
investigation of pragmatic representations such as Gricean enrichments. That is
not to say priming is without its limitations, however. Interpreting a failure to
observe priming may not be as simple as Branigan & Pickering (B&P) imply.
PMID- 29342736
TI - The relationship between priming and linguistic representations is mediated by
processing constraints.
AB - Understanding the nature of linguistic representations undoubtedly will benefit
from multiple types of evidence, including structural priming. Here, we argue
that successfully gaining linguistic insights from structural priming requires us
to better understand (1) the precise mappings between linguistic input and
comprehenders' syntactic knowledge; and (2) the role of cognitive faculties such
as memory and attention in structural priming.
PMID- 29342737
TI - Priming is swell, but it's far from simple.
AB - Clearly, structural priming is a valuable tool for probing linguistic
representation. But we don't think that the existing results provide strong
support for Branigan & Pickering's (B&P's) model, largely because the priming
effects are more confusing and diverse than their theory would suggest.
Fortunately, there are a number of other experimental tools available, and
linguists are increasingly making use of them.
PMID- 29342738
TI - Developmental psycholinguistics teaches us that we need multi-method, not single
method, approaches to the study of linguistic representation.
AB - In developmental psycholinguistics, we have, for many years, been generating and
testing theories that propose both descriptions of adult representations and
explanations of how those representations develop. We have learnt that
restricting ourselves to any one methodology yields only incomplete data about
the nature of linguistic representations. We argue that we need a multi-method
approach to the study of representation.
PMID- 29342739
TI - The malleability of linguistic representations poses a challenge to the priming
based experimental approach.
AB - Recent findings show that experience with a syntactic structure has long-term
consequences for how that structure will be processed in the future, which
suggests that linguistic representations are not static entities that can be
probed reliably without alteration. Thus, leveraging the effect of previous
exposure to a syntactic structure appears to be an inappropriate method for
studying invariant properties of language.
PMID- 29342740
TI - Setting the empirical record straight: Acceptability judgments appear to be
reliable, robust, and replicable.
AB - Branigan & Pickering (B&P) advocate the use of syntactic priming to investigate
linguistic representations and argue that it overcomes several purported
deficiencies of acceptability judgments. While we recognize the merit of drawing
attention to a potentially underexplored experimental methodology in language
science, we do not believe that the empirical evidence supports B&P's claims
about acceptability judgments. We present the relevant evidence.
PMID- 29342741
TI - Structural priming and the representation of language.
AB - Structural priming offers a powerful method for experimentally investigating the
mental representation of linguistic structure. We clarify the nature of our
proposal, justify the versatility of priming, consider alternative approaches,
and discuss how our specific account can be extended to new questions as part of
an interdisciplinary programme integrating linguistics and psychology as part of
the cognitive sciences of language.
PMID- 29342742
TI - Public health interventions can increase objective and perceived control by
supporting people to enact the choices they want to make.
AB - "Low-agency" public health interventions do not rely on individuals using their
personal resources to benefit. These help people enact the choices they wish to
make and are likely to increase objective and perceived control. Lower-agency
interventions have been criticised as constraining individual choice. Pepper &
Nettle show that this is unlikely to be the case.
PMID- 29342743
TI - The elusive constellations of poverty.
AB - Pepper & Nettle describe possible processes underlying what they call a
behavioral constellation of deprivation (BCD). Although we are certain about the
application of evolutionary models to our understanding of poverty, we are less
certain about the utility of behavioral constellations. The empirical record on
poverty-related behaviors is much more divergent and broad than such
constellations suggest.
PMID- 29342744
TI - From perceived control to self-control, the importance of cognitive and emotional
resources.
AB - Pepper & Nettle (P&N) suggest that the poor present a "contextually appropriate
response" to a perceived limited control and to a short life expectancy. We argue
that differences in health, behavior, or impaired economic decisions are better
explained by self-control. We discuss the implications of the differences between
these perspectives and present supporting findings from two intervention studies
with marginalized populations.
PMID- 29342745
TI - The behavioural constellation of deprivation: Compelling framework, messy
reality.
AB - Pepper & Nettle's (P&N's) argument is compelling, but apparently contradictory
data are easily found. Associations between socioeconomic status (SES) and
substance abuse are sometimes positive, the poor are sometimes eager to educate
their children, and perceptions of local mortality risk can be so distorted as to
constitute an implausible basis for contextually appropriate responding. These
anomalies highlight the need for more psychological work.
PMID- 29342746
TI - The behavioral constellation of deprivation may be best understood as risk
management.
AB - Although the authors make a compelling case that early-life deprivation leads to
present orientation, we believe that such behaviors may be better understood in
terms of an underlying risk-management strategy, in which those who experience
such deprivation are more risk-averse. The model we sketch accommodates the
authors' present-orientation observations and further explains differences in
risk preferences and social preferences.
PMID- 29342747
TI - Developing the behavioural constellation of deprivation: Relationships, emotions,
and not quite being in the present.
AB - Although it is a welcome and timely idea, the behavioural constellation of
deprivation (BCD) needs to explain how the development of personal control,
trust, and perception of future risk is mediated through relationships with
parents. Further, prioritising the present over the future may not be the essence
of this constellation; perhaps not quite being, either in the present or in the
future, is a better depiction.
PMID- 29342748
TI - Interpreting risky behavior as a contextually appropriate response: Significance
and policy implications beyond socioeconomic status.
AB - The significance of the contextually appropriate response perspective (CARP) can
be judged, in part, by its potential to stimulate new research and guide public
policy. To illustrate this potential, I move beyond socioeconomic status
differences in behavior and apply CARP to broader, policy-relevant issues in
criminology. In this area, CARP sheds new light on some old problems.
PMID- 29342749
TI - Evolutionary approaches to deprivation transform the ethics of policy making.
AB - When designing public policies, decision makers often rely on their own
behavioral preferences. Pepper & Nettle's (P&N's) theory suggests that these
preferences are unlikely to be appropriate when applied to a different
environment (e.g., a low-income environment with fewer career opportunities).
This theory has profound implications for the design and ethics of public
policies.
PMID- 29342750
TI - The physiological constellation of deprivation: Immunological strategies and
health outcomes.
AB - Physiology and behavior are best thought of as two aspects of the same biological
process, shaped simultaneously by natural selection. Like behavioral strategies,
ecological conditions may affect physiological strategies, leading to changes in
immunity and hormonal regulation. These alternate strategies help explain the
health correlations of deprivation and provide additional pathways for feedback
from early-life experiences.
PMID- 29342751
TI - Divergent life histories and other ecological adaptations: Examples of social
class differences in attention, cognition, and attunement to others.
AB - Many behavioral and psychological effects of socioeconomic status (SES), beyond
those presented by Pepper & Nettle cannot be adequately explained by life-history
theory. We review such effects and reflect on the corresponding ecological
affordances and constraints of low- versus high-SES environments, suggesting that
several ecology-specific adaptations, apart from life-history strategies, are
responsible for the behavioral and psychological effects of SES.
PMID- 29342752
TI - Uncertainty about future payoffs makes impatience rational.
AB - Uncertainty (i.e., variable payoffs with unknown probabilities) brings together a
number of features of the authors' argument. It leads to present bias, even for
completely rational agents with time-consistent preferences. As an evolutionary
product of Pleistocene climate instability, humans possess broad adaptations to
environmental uncertainty, giving rise to key features of the behavioral
constellation of deprivation (BCD).
PMID- 29342753
TI - Beyond personal control: The role of developing self-control abilities in the
behavioral constellation of deprivation.
AB - We agree with Pepper & Nettle that personal control is important in understanding
people's willingness to engage in future-oriented behavior. However, this does
not imply that self-control abilities play no role, for self-control abilities do
influence whether individuals engage in future-oriented behavior. Personal
control may also shape the development of self-control abilities, so contrasting
the two may be a false dichotomy.
PMID- 29342754
TI - Toward a balanced view of stress-adapted cognition.
AB - Pepper & Nettle's paper exemplifies an emerging resistance against an exclusive
focus on deficits in people who come from harsh environments. We extend their
model by arguing for a perspective that includes not only contextually
appropriate responses but also strengths - that is, enhanced mental skills and
abilities. Such a well-rounded approach can be leveraged in education, jobs, and
interventions.
PMID- 29342755
TI - What about the behavioral constellation of advantage?
AB - Many short-sighted behaviors are more common among poorer people. These behaviors
are neither evolutionarily nor historically unusual and have strong contemporary
encouragement. The bigger puzzle is their lower frequency among the affluent. The
behaviors also have clear cultural and normative aspects that limit the
usefulness of strictly individualist theories.
PMID- 29342756
TI - Predictability or controllability: Which matters more for the BCD?
AB - Pepper & Nettle's theory of the behavioral constellation of deprivation (BCD)
would benefit from teasing apart the conceptually distinct - although related -
constructs of predictability and control. Our commentary draws from prior
research conducted in the learning domain to demonstrate that predictability
moderates the effects of control and independently exerts a powerful influence on
outcomes relevant to the BCD.
PMID- 29342757
TI - Socioeconomic status, unpredictability, and different perceptions of the same
risk.
AB - In this commentary, we address three questions: (1) How might outcomes be
affected by the variation in the level of deprivation, rather than the average
level of deprivation? (2) Could there be differences in the subjective perception
of the same risk as either intrinsic or extrinsic, depending on people's
socioeconomic status (SES)? (3) What other psychological mechanisms might play a
role in influencing the psychology and behavior of people from deprived
backgrounds?
PMID- 29342758
TI - When does deprivation motivate future-oriented thinking? The case of climate
change.
AB - Pepper & Nettle overstate cross-domain evidence of present-oriented thinking
among lower-socioeconomic-status (SES) groups and overlook key social and
contextual drivers of temporal decision making. We consider psychological
research on climate change - a quintessential intertemporal problem that
implicates inequities and extrinsic mortality risk - documenting more future
oriented thinking among low- compared to high-SES groups.
PMID- 29342759
TI - Loss of control is not necessary to induce behavioral consequences of
deprivation: The case of religious fasting during Ramadan.
AB - Pepper & Nettle argue that the more present-oriented behavior associated with a
low socioeconomic status is an adaptive response to having relatively little
control over the future. However, a study of fasters during Ramadan shows that
self-imposed deprivation, which carries no implications regarding the ability to
realize deferred rewards, is associated with loss and risk aversion.
PMID- 29342760
TI - The uncontrollable nature of early learning experiences.
AB - Early learning experiences shape the development of the behavioral constellation
of deprivation (BCD) proposed by Pepper & Nettle (P&N). There is considerable
variability in early learning experiences across diverse socioeconomic status
(SES) backgrounds, particularly when it comes to language. Here, we discuss how
early learning experiences are beyond the control of the individual and
subsequently contribute to behaviors in P&N's constellation.
PMID- 29342761
TI - The "appropriate" response to deprivation: Evolutionary and ethical dimensions.
AB - Pepper & Nettle use an evolutionary framework to argue that "temporal
discounting" is an appropriate response to low socioeconomic status (SES), or
deprivation. We suggest some conceptual refinements to their "appropriate
response" perspective, with the hope that it usefully informs future research on
and public policy responses to the relationship between deprivation and temporal
discounting.
PMID- 29342762
TI - Both collection risk and waiting costs give rise to the behavioral constellation
of deprivation.
AB - Pepper & Nettle explain the behavioral constellation of deprivation (BCD) in
terms of differences in collection risk (i.e., the probability of collecting a
reward after some delay) between high- and low-socioeconomic-status (SES)
populations. We argue that a proper explanation should also include the costs of
waiting per se, which are paid even when the benefits are guaranteed.
PMID- 29342763
TI - Relative state, social comparison reactions, and the behavioral constellation of
deprivation.
AB - Pepper & Nettle compellingly synthesize evidence indicating that temporal
discounting is a functional, adaptive response to deprivation. In this
commentary, we underscore the importance of the psychology of relative state,
which is an index of relative competitive (dis)advantage. We then highlight two
proximate emotional social comparison reactions linked with relative state -
personal relative deprivation and envy - that may play an important role in the
deprivation-discounting link.
PMID- 29342764
TI - Cultural consonance, deprivation, and psychological responses for niche
construction.
AB - Cultural consonance is a measure of culturally encoded goals relevant to
psychological, behavioral, and health responses to deprivation. Similar to
extrinsic mortality, low cultural consonance and an associated inability to
predict adaptive outcomes may activate impulsivity, delay discounting, and reward
seeking. Low cultural consonance could promote "fast life history" in low-quality
environments and motivate cultural niche construction for local adaptation.
PMID- 29342765
TI - Stuff goes wrong, so act now.
AB - Pepper & Nettle make an ambitious and compelling attempt to isolate a common
cause of what they call the behavioral constellation of deprivation. We agree
with the authors that limited control can indeed help explain part of the
difference in observed present-oriented behavior between the poor and the rich.
However, we suggest that mortality risk is not the primary mechanism leading to
this apparent impatience.
PMID- 29342766
TI - Deprived, but not depraved: Prosocial behavior is an adaptive response to lower
socioeconomic status.
AB - Individuals of lower socioeconomic status (SES) display increased attentiveness
to others and greater prosocial behavior compared to individuals of higher SES.
We situate these effects within Pepper & Nettle's contextually appropriate
response framework of SES. We argue that increased prosocial behavior is a
contextually adaptive response for lower-SES individuals that serves to increase
control over their more threatening social environments.
PMID- 29342767
TI - It's not just about the future: The present payoffs to behaviour vary in degree
and kind between the rich and the poor.
AB - Pepper & Nettle offer a nuanced and humane view on poverty that should be
required reading for policy makers, particularly those interested in "behaviour
change" policy. We suggest, however, that the emphasis on "future-discounting" in
this paper downplays the importance of differences in the payoffs to behaviours
in the present and how these payoffs may be realised in different currencies.
PMID- 29342768
TI - Intertemporal impulsivity can also arise from persistent failure of long-term
plans.
AB - We suggest that steep intertemporal discounting in individuals of low
socioeconomic status (SES) may arise as a rational metacognitive adaptation to
experiencing planning and control failures in long-term plans. Low SES
individuals' plans fail more frequently because they operate close to budgetary
boundaries, in turn because they consistently operate with limited budgets of
money, status, trust, or other forms of social utility.
PMID- 29342769
TI - The link between deprivation and its behavioural constellation is confounded by
genetic factors.
AB - Most research cited throughout Pepper & Nettle's (P&N's) target article is
correlational and suffers from a serious genetic confound that renders it of
little evidentiary value. Of correlational findings that are not confounded, P&N
ignore examples that contradict their model. Further, P&N's claim that
evolutionary models explaining between-species differences in behaviour can be
used to understand that corresponding individual differences lack any evidence.
PMID- 29342770
TI - Health behaviour, extrinsic risks, and the exceptions to the rule.
AB - Pepper & Nettle make a compelling case for how evolutionary thinking can help
explain behaviours that cluster with deprivation. The role of extrinsic mortality
risk in driving behaviour is probably important, but strong evidence is still
lacking. By thinking carefully about behaviours seemingly at odds with an
evolutionary life history perspective, we can gain important insights that will
help refine theory.
PMID- 29342771
TI - Intergenerational capital flows are central to fitness dynamics and adaptive
evolution in humans.
AB - Human fitness dynamics are uniquely and profoundly governed by the flow of
capital to subsequent generations. Low socioeconomic status individuals may
possess limited capacity to direct capital to descendants and may respond to such
constraints adaptively or maladaptively. Mitigation of capital constraints may
provide practicable routes to alleviation of the behavioural constellation of
deprivation.
PMID- 29342772
TI - Epigenetic-based hormesis and age-dependent altruism: Additions to the
behavioural constellation of deprivation.
AB - We support Pepper and Nettle's (P&N's) hypothesised adaptive responses to
deprivation. However, we argue that adaptive responses to stress shift with age.
Specifically, present-oriented behaviours are adaptive for young people (e.g., in
terms of mating and reproduction) but costly for older people in deprived
communities who would benefit from investing in grandchildren. Epigenetic
mechanisms may be responsible for age-related tactical shifts.
PMID- 29342773
TI - Strengths, altered investment, risk management, and other elaborations on the
behavioural constellation of deprivation.
AB - We are grateful to have received so many insightful commentaries from interested
colleagues regarding our proposed behavioural constellation of deprivation (BCD)
and our thoughts on its causes and consequences. In this response article, we
offer some clarifications regarding our perspective and tackle some common
misperceptions, including, for example, assumptions that the BCD is adaptive and
that it should include all behaviours that vary with socioeconomic status. We
then welcome some excellent proposals for extensions and modifications of our
ideas, such as the conceptualisation of the BCD as a risk-management strategy and
the calls for a greater focus on strengths and differential investment rather
than deficits and disinvestment. Finally, we highlight some insightful
explorations of the implications of our ideas for ethics, policy, and practice.
PMID- 29342774
TI - A social dimension to enjoyment of negative emotion in art reception.
AB - The proposed model overlooks the contribution of a relational/prosocial dimension
to the enjoyment of negative emotion in art reception. Negative experiences have
a unique capacity to build social bonds and may also increase motivation to
"connect" with the artist. This affiliative motivation ensures that people
experience an artwork as more emotional, more intense, more interesting, and
ultimately more rewarding.
PMID- 29342775
TI - Artistic misunderstandings: The emotional significance of historical learning in
the arts.
AB - The Distancing-Embracing model does not have the conceptual resources to explain
artistic misunderstandings and the emotional consequences of historical learning
in the arts. Specifically, it suggests implausible predictions about emotional
distancing caused by art schemata (e.g., misunderstandings of artistic intentions
and contexts). These problems show the need for further inquiries into how
historical contextualization modulates negative emotions in the arts.
PMID- 29342776
TI - Reconciling an underlying contradiction in the Distancing-Embracing model.
AB - The Distancing-Embracing model proposes that negative emotions embedded in
literary works can be rewarding. This is consistent with a holistic ontology in
the German Romantic tradition. However, the application of cognitive psychology
to explain experiences of aesthetic pleasure is problematic because it is founded
on a mechanistic Enlightenment epistemology. The appreciation of negative
emotions requires cognitive elaboration and closure, whereas hedonistic reward is
contingent on the reader's needs, in the moment, for pleasure or distraction.
PMID- 29342777
TI - Positivity versus negativity is a matter of timing.
AB - "Negative" emotions are never purely negative. They attract attention at the very
least and often stay attractive enough to make rehearsing them an addictive
activity. As the authors point out, they also counteract a relentless tendency
for positive emotions to become boring. Analysis in terms of reward suggests why
this tendency occurs and how symbiosis with negative emotions may arise, in art
and in life.
PMID- 29342778
TI - Considering the filmmaker: Intensified continuity, narrative structure, and the
Distancing-Embracing model.
AB - Menninghaus et al. pose two open-ended questions: To what extent do formal
elements of art elicit negative affect, and do artists try to elicit this
response in a theory-based or intuitive manner? For popular movies, we argue that
the consideration of their construction is prior to the consideration of the
experience that they evoke.
PMID- 29342779
TI - Emotional granularity and the musical enjoyment of sadness itself.
AB - We contest the claim that musically induced sadness cannot be enjoyable in
itself. This possibility is supported by closer attention to a musical experience
as well as cases of affective reversal, such as the "hedonic flip" of painful
feelings. We propose that the affective reversal of sadness in music is due to
the high granularity of musically induced emotion.
PMID- 29342780
TI - The urge to judge: Why the judgmental attitude has anything to do with the
aesthetic enjoyment of negative emotions.
AB - Based on arguments from both philosophical and empirical aesthetics, we hereby
propose that the enjoyment of negative emotions in art and fiction is distinct
from the immediate pleasure deriving from sensory features, because it requires a
conscious, intentional attitude toward the object. This attitude is linked with
the compelling goal of providing a judgment of liking, beauty, perfection, or
similar.
PMID- 29342781
TI - Orange is the new aesthetic.
AB - The Distancing-Embracing model proposes that negative emotions are constitutive
of aesthetic experiences. This move is welcome and adds depth to empirical
aesthetics. However, the model's emphasis on temporality challenges how best to
think of static art forms. I suggest that "decisive" and "distilled" moments
dilate time in the viewer's mind and might allow the model to accommodate
photography and painting.
PMID- 29342782
TI - Distancing, not embracing, the Distancing-Embracing model of art reception.
AB - Despite denials in the target article, the Distancing-Embracing model appeals to
compensatory ideas in explaining the appeal of artworks that elicit negative
affect. The model also appeals to the deflationary effects of psychological
distancing. Having pointed to the famous rejection in the 1960s of the view that
aesthetic experience involves psychological distancing, I suggest that "distance"
functions here as a weak metaphor that cannot sustain the explanatory burden the
theory demands of it.
PMID- 29342783
TI - Boredom in art.
AB - In the light of recent findings on the nature of boredom, I argue that boredom is
a potentially useful emotion in art reception and show how the Distancing
Embracing model can be applied to boredom.
PMID- 29342784
TI - You are not alone - Social sharing as a necessary addition to the Embracing
factor.
AB - I argue that the Embracing factor cannot be adequately conceptualized without
taking into account the regulatory power of the social sharing of emotions.
Humans tend to share their negative emotions with close others, and they benefit
from it. I outline how this mechanism works in art reception by regulating and
transforming negative emotions into positive experiences.
PMID- 29342785
TI - Individual differences in embracing negatively valenced art: The roles of
openness and sensation seeking.
AB - We elaborate on the role of individual differences in the processing mechanisms
outlined by the Distancing-Embracing model. The role of openness is apparent in
appreciating meaning-making art that elicits interest, feeling moved, and mixed
emotions. The influence of sensation seeking is likely to manifest in thrill
chasing art that draws on the arousing interplay of positive and negative
emotions.
PMID- 29342786
TI - Fiction as a bridge to action.
AB - We propose an extension of the Distancing-Embracing model to the use of stories
for prosocial ends. Specifically, audiences may find stories of individuals in
need too emotionally overwhelming. Audiences may attempt to regulate or reduce
negative emotions, which can reduce empathy and willingness to help. Through
distancing, fictionalized accounts may counteract this tendency and thus increase
prosocial behavior.
PMID- 29342787
TI - Empathy as a guide for understanding the balancing of Distancing-Embracing with
negative art.
AB - We connect the Distancing-Embracing model to theoretical and empirical evidence
regarding empathy, which raises questions about the ordering and modulation of
distancing in particular. Namely, distancing may not be a binary, continuously
on/off process. Rather we suggest that changes in distancing as actualized via
the relation between the individual and art (e.g., through empathy) might be a
useful avenue for further consideration.
PMID- 29342788
TI - Live theatre as exception and test case for experiencing negative emotions in
art.
AB - Distancing and then embracing constitutes a useful way of thinking about the
paradox of aesthetic pleasure. However, the model does not account for live
theatre. When live actors perform behaviors perceptually close to real life and
possibly really experienced by the actors, audiences may experience autonomic
reactions, with less distance, or may have to distance post
experiencing/embracing their emotions.
PMID- 29342789
TI - Art enhances meaning by stimulating integrative complexity and aesthetic
interest.
AB - Menninghaus et al. portrayed meaning in art as a vehicle for transforming
negative emotions into pleasure. Although it is intuitively appealing that
meaningful experiences should feel good, meaningfulness does not necessarily
entail pleasure or positive emotions. Whereas easily comprehended art may elicit
pleasure, meaningfulness is more closely tied to challenge and interest than to
pleasure.
PMID- 29342790
TI - Context matters: How macroeconomic forces may alter the reception of negative
emotions in art.
AB - Menninghaus et al. offer a comprehensive model to explain why people pursue
darker emotions in art, but we believe they underplay the considerable role of
situational factors in driving these preferences. In particular, changing mood
states are likely to shape artistic preferences, in large part because positive
mood states act as a protective buffer against otherwise aversive experiences.
PMID- 29342791
TI - "Negative emotions" live in stories, not in the hearts of readers who enjoy them.
AB - The commendably ambitious project by Menninghaus et al. fails because its main
connective tissue - "negative emotions" - is beyond the grasp of the authors'
largely literary approach. The critique focuses on their treatment of the Paradox
of Fiction, the neglect of the biological, adaptive nature of emotions, and the
absence of convincing empirical support for key aspects of the proposed model.
PMID- 29342792
TI - What is art and how does it differ from aesthetics?
AB - Art objects differ from other objects because they are intentionally created to
embody a producer's (i.e., artist's) expression. Hence, art objects are social
objects whose appeal and value are determined largely by the strategic
interaction between the artist and the audience. I discuss several aspects of how
strategic interaction can affect an art object's perceived value and aesthetic
appeal.
PMID- 29342793
TI - The paradox of tragedy and emotional response to simulation.
AB - The insightful analysis of Menninghaus et al. could be deepened and rendered more
systematic by recognizing that our emotional enjoyment of tragedy - and our
response to fiction more generally - are versions of what happens with
simulation. They derive from the operation and evolutionary function of
simulation. Once we understand emotion in simulation, we largely understand
emotion in tragedy (and fiction).
PMID- 29342794
TI - The enjoyment of negative emotions in the experience of magic.
AB - Theatrical magic is designed to elicit negative emotions such as feelings of
vulnerability, loss of control, apprehension, fear, confusion, and bafflement.
This commentary suggests that the Distancing-Embracing model can help us
understand how the experience of magic can be aesthetically pleasurable, not
despite, rather thanks to, some of the strong negative emotions it provokes.
PMID- 29342795
TI - Psychological models of art reception must be empirically grounded.
AB - We commend Menninghaus et al. for tackling the role of negative emotions in art
reception. However, their model suffers from shortcomings that reduce its
applicability to empirical studies of the arts: poor use of evidence, lack of
integration with other models, and limited derivation of testable hypotheses. We
argue that theories about art experiences should be based on empirical evidence.
PMID- 29342796
TI - Art and fiction are signals with indeterminate truth values.
AB - Menninghaus et al. distinguish art from fiction, but no current arguments or data
suggest that the concept of art can be meaningfully circumscribed. This is a
problem for aesthetic psychology. I sketch a solution by rejecting the
distinction: Unlike most animal communication, in which signals are either true
or false, art and fiction consist of signals without determinate truth values.
PMID- 29342797
TI - Does art expertise facilitate distancing?
AB - With respect to the Distancing-Embracing model, we discuss whether experts with
well-developed and highly accessible schemata that lend themselves to distancing
have initial affective reactions similar to those of novices, who lack access to
well-developed distancing mechanisms, and whether differences between experts'
and novices' responses are apparent only after distancing mechanisms have had a
chance to do their work. We revisit findings from Leder et al. (2014) and discuss
the role of mixed emotions and fluency.
PMID- 29342798
TI - Art as emotional exploration.
AB - The Roman poet Horace said poetry gives pleasure and instructs. A more
informative theory is that poetry and art, in general, are less about pleasure
than about exploration of emotions. Literary authors concentrate on negative
emotions, seemingly to try and understand them. In two studies, reading literary
art enabled the transformation of selfhood, not by being instructed but by people
changing in their own ways.
PMID- 29342799
TI - Being moved is a positive emotion, and emotions should not be equated with their
vernacular labels.
AB - As evidence for the second process of the Embracing factor, the target article
characterizes being moved as a mixed emotion linked to sadness through metonymy.
We question these characterizations and argue that emotions should not be equated
with their vernacular labels.
PMID- 29342800
TI - Genre scripts and appreciation of negative emotion in the reception of film.
AB - The Distancing-Embracing model reserves a role for genre scripts in the hedonic
valuation of negative emotion in art. Genre scripts, as defined in the target
article, leave higher-level recipient intuitions out of scope. We argue that, in
film genre scripts, lower-level stylistic features lend access to more complex
conceptual knowledge, including pragmatic principles. The argument implies a
consideration of the communicative dimension of aesthetic works, which could
strengthen both factors of the Distancing-Embracing model.
PMID- 29342801
TI - Parental response to baby cry involves brain circuits for negative emotion
Distancing-Embracing.
AB - The "art form" of parent-infant bonding critically involves baby conveying
negative emotions - literally compelling parents to respond and provide care.
Current research on the brain basis of parenting is combining brain imaging with
social, cognitive, and behavioral analyses to understand how parental brain
circuits regulate thoughts and behavior in mental health, risk, and resilience.
Understanding the parental brain may contribute to solving the long-standing
paradox of self-sought hedonic exposure to negative emotions in art reception.
PMID- 29342802
TI - Art reception as an interoceptive embodied predictive experience.
AB - In the Distancing-Embracing model, an explanation is proposed for the apparent
paradox that is the enjoyment of negative emotional states in art reception.
Here, we argue for the advantages of grounding the psychological dynamics
described in the model in established and empirically testable frameworks of
brain functioning by thinking of art reception as an embodied experience guided
by predictive coding.
PMID- 29342803
TI - Explaining the enjoyment of negative emotions evoked by the arts: The need to
consider empathy and other underlying mechanisms of emotion induction.
AB - Any model aiming to explain the enjoyment of negative emotions in the context of
the arts should consider how works of art are able to induce emotional responses
in the first place. For instance, research on empathy and the arts suggests that
the psychological processes that mediate the enjoyment of sadness and horror may
be fundamentally different.
PMID- 29342804
TI - Tuning in to art: A predictive processing account of negative emotion in art.
AB - We use the example of art-derived solace to discuss a broader mechanism by which
negative affect is instrumental in creating positive appreciation of artworks.
Based on the theory of predictive processing, we argue that increasing attunement
or reduction of prediction errors, which implies increasing validation of the
agents (models), is experienced as positive, even if the artwork's content is
negative.
PMID- 29342805
TI - Embracing nonfiction: How to extend the Distancing-Embracing model.
AB - The Distancing factor of Menninghaus et al.'s model includes schemas that remind
consumers that the representation is fictional. Although they claim that these
schemas are crucial to the functioning of the Embracing factor of the model, we
argue that consumers can have similar responses to nonfictional representations.
We urge the authors to expand their model to include such cases.
PMID- 29342806
TI - Negative emotions in art reception: Refining theoretical assumptions and adding
variables to the Distancing-Embracing model.
AB - While covering all commentaries, our response specifically focuses on the
following issues: How can the hypothesis of emotional distancing (qua art
framing) be compatible with stipulating high levels of felt negative emotions in
art reception? Which concept of altogether pleasurable mixed emotions does our
model involve? Can mechanisms of predictive coding, social sharing, and immersion
enhance the power of our model?
PMID- 29342807
TI - Beyond aerodigestion: Exaptation of feeding-related mouth movements for social
communication in human and nonhuman primates.
AB - Three arguments are advanced from human and nonhuman primate infancy research for
the exaptation of ingestive mouth movements (tongue protrusion and lip smacking)
for the purposes of social communication: their relation to affiliative
behaviours, their sensitivity to social context, and their role in social
development. Although these behaviours may have an aerodigestive function, such
an account of their occurrence is only partial.
PMID- 29342808
TI - Philosopher's disease and its antidote: Perspectives from prenatal behavior and
contagious yawning and laughing.
AB - Accounts of behavior, including imitation, often suffer from philosopher's
disease: the unnecessary, inappropriate, theoretically driven explanation of
behavior in terms of cognition, rationality, and consciousness. Embryos are
perversely unphilosophical and unpsychological, starting to move before they
receive sensory input. Postnatal contagious yawning and laughing indicate that
pseudo-imitative behavior can occur without conscious intent or other higher
order cognitive process.
PMID- 29342809
TI - Beyond sensorimotor imitation in the neonate: Mentalization psychotherapy in
adulthood.
AB - Despite the persuasiveness of Keven & Akins' (K&A) review, we argue that
mentalization, or the ability to interpret the mental states of oneself and
others, is required to construct the neonate mind, going far beyond sensorimotor
imitation. This concept, informed by certain psychoanalytic and attachment
theories, has produced a form of therapy called mentalization-based
psychotherapy, which aims to improve emotional regulation. Our aim here is to
shed light on a form of neonatal imitation that goes beyond sensorimotor
imitation.
PMID- 29342810
TI - "It takes two to know one" - Tongue protrusion-retraction is only one small facet
of early intersubjectivity.
AB - Tongue protrusion-retraction is critical to early nutrition but is also a
gustatory-olfactory aspect of early infant social behaviour that is, in part,
reliant on pre-natal exposure and learning. Most early development is necessarily
dyadic and intrinsically associated with other aspects of social functioning.
PMID- 29342811
TI - Spontaneous communication and infant imitation.
AB - Infant behavior is viewed in a social-communicative context centered on the
phenomenon of spontaneous communication. Symbolic communication is learned and
culturally structured, intentional, consists of symbols, and is propositional in
content. In contrast, spontaneous communication is innate in both its sending
(display) and receiving (preattunement) aspects, non-intentional, consists of
signs, and is non-propositional or emotional in content. It underlies infant
imitation, interactional synchrony, primary intersubjectivity, emotional empathy,
and mirror neurons; and it is associated with oxytocin.
PMID- 29342812
TI - A major blow to primate neonatal imitation and mirror neuron theory.
AB - Keven & Akins' (K&A's) compelling new hypothesis explaining the developmental and
neural basis of neonatal tongue protrusion has important implications for current
understanding of primate imitation and the explanatory value of mirror neurons.
If correct, this hypothesis eliminates a major source of evidence for neonatal
imitation. I explore the implications this has for mirror neuron research and the
arguments building upon them.
PMID- 29342813
TI - Mommy or me? Who is the agent in a sense of agency in infant orofacial
stereotypies?
AB - That neonates imitate is an assertion that lacks supporting evidence. Orofacial
stereotypies are critical to optimizing food rejection. Matching of tongue
protrusion is not imitation, but a manifestation of the infant's arousal by the
modeler's exhibition of the same behavior. The support for the nativist assertion
that newborn infants imitate is not compelling, and we should proceed on the
assumption that they do not.
PMID- 29342814
TI - Do innate stereotypies serve as a basis for swallowing and learned speech
movements?
AB - Keven & Akins suggest that innate stereotypies like TP/R may participate in the
acquisition of tongue control. This commentary examines this claim in the context
of speech motor learning and biomechanics, proposing that stereotypies could
provide a basis for both swallowing and speech movements, and provides
biomechanical simulation results to supplement neurological evidence for
similarities between the two behaviors.
PMID- 29342815
TI - Infant orofacial movements: Inputs, if not outputs, of early imitative ability?
AB - According to Keven & Akins (K&A), infant orofacial gestures may not reflect
imitative responses. Here, we emphasise that these actions nonetheless represent
a significant feature of the infant's early sensorimotor experience, and
therefore may play a key role in the development of imitative capacities. We
discuss how the ideas proposed in the target article could contribute
substantially to experiential accounts of imitation.
PMID- 29342816
TI - Animal studies help clarify misunderstandings about neonatal imitation.
AB - Empirical studies are incompatible with the proposal that neonatal imitation is
arousal driven or declining with age. Nonhuman primate studies reveal a
functioning brain mirror system from birth, developmental continuity in imitation
and later sociability, and the malleability of neonatal imitation, shaped by the
early environment. A narrow focus on arousal effects and reflexes may grossly
underestimate neonatal capacities.
PMID- 29342817
TI - Beyond neonatal imitation: Aerodigestive stereotypies, speech development, and
social interaction in the extended perinatal period.
AB - In our target article, we argued that the positive results of neonatal imitation
are likely to be by-products of normal aerodigestive development. Our hypothesis
elicited various responses on the role of social interaction in infancy, the
methodological issues about imitation experiments, and the relation between the
aerodigestive theory and the development of speech. Here we respond to the
commentaries.
PMID- 29342818
TI - The functional and developmental role of imitation in the (a)typical brain.
AB - Keven & Akins (K&A) propose a biologically plausible view of neonatal imitation
based on the analysis of sensorimotor development. Here, we consider imitation in
the general context of motor cognition, taking examples from both typical and
atypical development. Specifically, we will discuss the functional role of
imitation, its multi-level nature, and its anomalous features in autism.
PMID- 29342819
TI - When dyadic interaction is the context: Mimicry behaviors on the origin of
imitation.
AB - Keven & Akins (K&A) redefine some of the neonatal imitation (NI) behaviors as
developmental stereotypes. From a neuroconstructivist framework, those early
gestures are also far from being considered as imitative behaviors. The cognitive
substrate of imitation requires an interactive context to develop. Prior to
intentional imitation, the dyad shows mimicry behaviors, which are automatic, but
do not fade through development.
PMID- 29342820
TI - There is no compelling evidence that human neonates imitate.
AB - Keven & Akins (K&A) propose that neonatal "imitation" is a function of newborns'
spontaneous oral stereotypies and should be viewed within the context of normal
aerodigestive development. Their proposal is in line with the result of our
recent large longitudinal study that found no compelling evidence for neonatal
imitation. Together, these works prompt reconsideration of the developmental
origin of genuine imitation.
PMID- 29342821
TI - Multisensory control of ingestive movements and the myth of food addiction in
obesity.
AB - Some individuals have a neurogenetic vulnerability to developing strong
facilitation of ingestive movements by learned configurations of biosocial
stimuli. Condemning food as addictive is mere polemic, ignoring the
contextualised sensory control of the mastication of each mouthful. To beat
obesity, the least fattening of widely recognised eating patterns needs to be
measured and supported.
PMID- 29342822
TI - The case against newborn imitation grows stronger.
AB - The claim that human newborns imitate is widely accepted and influential. Yet
reliable evidence that newborns match modeled behaviors is limited, and there is
no empirically based explanation of how the knowledge that imitation requires
could develop before birth. In their target article, Keven & Akins (K&A)
contribute important new evidence to an alternative account of newborns' matching
that challenges the newborn imitation claim.
PMID- 29342823
TI - Elements of a comprehensive theory of infant imitation.
AB - Imitation is central to human development. Imitation involves mapping between the
perception and production of actions. Imitation after delays implicates preverbal
memory. Imitation of people informs us about infants' processing of social
events. A comprehensive theory needs to account for the origins, mechanisms, and
functions of imitation. Neonatal imitation illuminates how the initial state
engenders and supports rapid social learning.
PMID- 29342824
TI - Ecological validity, embodiment, and killjoy explanations in developmental
psychology.
AB - Keven & Akins (K&A) present a compelling alternative to the case for neonatal
orofacial imitation, offered by Meltzoff and Moore. However, they provide little
concerning what lessons their proposal has to offer developmental psychology more
generally. I suggest three candidates and elaborate on how they raise outstanding
methodological and philosophical questions for the approach taken in the target
article.
PMID- 29342825
TI - "What" matters more than "Why" - Neonatal behaviors initiate social responses.
AB - Newborns are born into a social environment that dynamically responds to them.
Newborn behaviors may not have explicit social intentions but will nonetheless
affect the environment. Parents contingently respond to their child, enabling
newborns to learn about the consequences of their behaviors and encouraging the
behavior itself. Consequently, newborn behaviors may serve both biological and
social-cognitive purposes during development.
PMID- 29342826
TI - An unsettled debate: Key empirical and theoretical questions are still open.
AB - Debates about neonatal imitation remain more open than Keven & Akins (K&A) imply.
K&A do not recognize the primacy of the question concerning differential
imitation and the links between experimental designs and more or less plausible
theoretical assumptions. Moreover, they do not acknowledge previous theorizing on
spontaneous behavior, the explanatory power of entrainment, and subtle
connections with social cognition.
PMID- 29342827
TI - Does early motor development contribute to speech perception?
AB - At the end of the target article, Keven & Akins (K&A) put forward a challenge to
the developmental psychology community to consider the development of complex
psychological processes - in particular, intermodal infant perception - across
different levels of analysis. We take up that challenge and consider the
possibility that early emerging stereotypies might help explain the foundations
of the link between speech perception and speech production.
PMID- 29342828
TI - Turning the tide: A plea for cognitively lean interpretations of infant
behaviour.
AB - Keven & Akins (K&A) revisit the controversial subject of neonatal imitation
through analysing the physiological foundations of neonatal spontaneous
behaviour. Consequently, they regard imitative capacities in neonates as
unlikely. We welcome this approach as an overdue encouragement to refuse
cognitively rich interpretations as far as cognitively lean interpretations are
conceivable, and apply this rationale to other phenomena in early childhood
development.
PMID- 29342829
TI - July 2017 Editor-in-Chief Letter.
PMID- 29342830
TI - Methods to Improve Osseointegration of Dental Implants in Low Quality (Type-IV)
Bone: An Overview.
AB - Nowadays, dental implants have become more common treatment for replacing missing
teeth and aim to improve chewing efficiency, physical health, and esthetics. The
favorable clinical performance of dental implants has been attributed to their
firm osseointegration, as introduced by Branemark in 1965. Although the survival
rate of dental implants over a 10-year observation has been reported to be higher
than 90% in totally edentulous jaws, the clinical outcome of implant treatment is
challenged in compromised (bone) conditions, as are frequently present in elderly
people. The biomechanical characteristics of bone in aged patients do not offer
proper stability to implants, being similar to type-IV bone (Lekholm & Zarb
classification), in which a decreased clinical fixation of implants has been
clearly demonstrated. However, the search for improved osseointegration has
continued forward for the new evolution of modern dental implants. This
represents a continuum of developments spanning more than 20 years of research on
implant related-factors including surgical techniques, implant design, and
surface properties. The methods to enhance osseointegration of dental implants in
low quality (type-IV) bone are described in a general manner in this review.
PMID- 29342831
TI - Refugee Health: An Ongoing Commitment and Challenge.
AB - Refugees represent a diverse group of displaced individuals with unique health
issues and disease risks. The obstacles facing this population have their origins
in war, violence, oppression, exploitation, and fear of persecution. Regardless
of country of origin, a common bond exists, with refugees often confronting
inadequate healthcare resources, xenophobia, discrimination, and a complex web of
legal barriers in their new homelands. In many cases, the plight of refugees is
multigenerational, manifesting as mental health issues, abuse, poverty, and
family disruption. The health trajectory of refugees remains an ongoing
commitment and challenge.
PMID- 29342832
TI - Development of an Internal Real-Time Wireless Diagnostic Tool for a Proton
Exchange Membrane Fuel Cell.
AB - To prolong the operating time of unmanned aerial vehicles which use proton
exchange membrane fuel cells (PEMFC), the performance of PEMFC is the key.
However, a long-term operation can make the Pt particles of the catalyst layer
and the pollutants in the feedstock gas bond together (e.g., CO), so that the
catalyst loses reaction activity. The performance decay and aging of PEMFC will
be influenced by operating conditions, temperature, flow and CO concentration.
Therefore, this study proposes the development of an internal real-time wireless
diagnostic tool for PEMFC, and uses micro-electro-mechanical systems (MEMS)
technology to develop a wireless and thin (<50 MUm) flexible integrated
(temperature, flow and CO) microsensor. The technical advantages are (1)
compactness and three wireless measurement functions; (2) elastic measurement
position and accurate embedding; (3) high accuracy and sensitivity and quick
response; (4) real-time wireless monitoring of dynamic performance of PEMFC; (5)
customized design and development. The flexible integrated microsensor is
embedded in the PEMFC, three important physical quantities in the PEMFC, which
are the temperature, flow and CO, can be measured simultaneously and instantly,
so as to obtain the authentic and complete reaction in the PEMFC to enhance the
performance of PEMFC and to prolong the service life.
PMID- 29342833
TI - Structural Determination of Ruthenium Complexes Containing Bi-Dentate Pyrrole
Ketone Ligands.
AB - A series of ruthenium compounds containing a pyrrole-ketone bidentate ligand, 2
(2'-methoxybenzoyl)pyrrole (1), have been synthesized and characterized. Reacting
1 with [(eta6-cymene)RuCl2]2 and RuHCl(CO)(PPh3)3 generated Ru(eta6-cymene)[C4H3N
2-(CO-C6H4-2-OMe)]Cl (2) and {RuCl(CO)(PPh3)2[C4H3N-2-(COC6H4-2-OMe)]} (3),
respectively, in moderate yields. Successively reacting 2 with sodium cyanate and
sodium azide gave {Ru(eta6-cymene)[C4H3N-2-(CO-C6H4-2-OMe)]X} (4, X=OCN; 5, X=N3)
with the elimination of sodium chloride. Compounds 2-5 were all characterized by
1H and 13C-NMR spectra and their structures were also determined by X-ray single
crystallography.
PMID- 29342835
TI - Small Peptides Able to Suppress Prostaglandin E2 Generation in Renal Mesangial
Cells.
AB - Peptide drug discovery may play a key role in the identification of novel
medicinal agents. Here, we present the development of novel small peptides able
to suppress the production of PGE2 in mesangial cells. The new compounds were
generated by structural alterations applied on GK115, a novel inhibitor of
secreted phospholipase A2, which has been previously shown to reduce PGE2
synthesis in rat renal mesangial cells. Among the synthesized compounds, the
tripeptide derivative 11 exhibited a nice dose-dependent suppression of PGE2
production, similar to that observed for GK115.
PMID- 29342834
TI - Facial Bone Reconstruction Using both Marine or Non-Marine Bone Substitutes:
Evaluation of Current Outcomes in a Systematic Literature Review.
AB - The aim of the present investigation was to systematically analyse the literature
on the facial bone reconstruction defect using marine collagen or not and to
evaluate a predictable treatment for their clinical management. The revision has
been performed by searched MEDLINE and EMBASE databases from 2007 to 2017.
Clinical trials and animal in vitro studies that had reported the application of
bone substitutes or not for bone reconstruction defect and using marine collagen
or other bone substitute material were recorded following Preferred Reporting
Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The first
selection involved 1201 citations. After screening and evaluation of suitability,
39 articles were added at the revision process. Numerous discrepancies among the
papers about bone defects morphology, surgical protocols, and selection of
biomaterials were found. All selected manuscripts considered the final clinical
success after the facial bone reconstruction applying bone substitutes. However,
the scientific evidence regarding the vantage of the appliance of a biomaterial
versus autologous bone still remains debated. Marine collagen seems to favor the
dimensional stability of the graft and it could be an excellent carrier for
growth factors.
PMID- 29342836
TI - Cool-Climate Red Wines-Chemical Composition and Comparison of Two Protocols for
1H-NMR Analysis.
AB - This study investigates the metabolome of 26 experimental cool-climate wines made
from 22 grape varieties using two different protocols for wine analysis by proton
nuclear magnetic resonance (1H-NMR) spectroscopy. The wine samples were analyzed
as-is (wet) and as dried samples. The NMR datasets were preprocessed by alignment
and mean centering. No normalization or scaling was performed. The "wet" method
preserved the inherent properties of the samples and provided a fast and
effective overview of the molecular composition of the wines. The "dried" method
yielded a slightly better sensitivity towards a broader range of the compounds
present in wines. A total of 27 metabolites including amino acids, organic acids,
sugars, and alkaloids were identified in the 1H-NMR spectra of the wine samples.
Principal component analysis was performed on both NMR datasets evidencing well
defined molecular fingerprints for 'Baco Noir', 'Bolero', 'Cabernet Cantor',
'Cabernet Cortis', 'Don Muscat', 'Eszter', 'Golubok', 'New York Muscat',
'Regent', 'Rondo', 'Triomphe d'Alsace', 'Precose Noir', and 'Vinoslivy' wines.
Amongst the identified metabolites, lactic acid, succinic acid, acetic acid,
gallic acid, glycerol, and methanol were found to drive sample groupings. The 1H
NMR data was compared to the absolute concentration values obtained from a
reference Fourier transform infrared method, evidencing a high correlation.
PMID- 29342837
TI - Effect of Exposed Surface Area, Volume and Environmental pH on the Calcium Ion
Release of Three Commercially Available Tricalcium Silicate Based Dental Cements.
AB - Tricalcium silicate cements (TSC) are used in dental traumatology and endodontics
for their bioactivity which is mostly attributed to formation of calcium
hydroxide during TSC hydration and its subsequent release of calcium and
hydroxide ions. The aim of this study was to determine the effect of volume
(Vol), exposed surface area (ESA) and pH of surrounding medium on calcium ion
release. Three commercially available hydraulic alkaline dental cements were
mixed and condensed into cylindrical tubes of varying length and diameter (n =
6/group). For the effect of ESA and Vol, tubes were immersed in 10 mL of
deionized water. To analyze the effect of environmental pH, the tubes were
randomly immersed in 10 mL of buffer solutions with varying pH (10.4, 7.4 or
4.4). The solutions were collected and renewed at various time intervals. pH
and/or calcium ion release was measured using a pH glass electrode and atomic
absorption spectrophotometer respectively. The change of pH, short-term calcium
ion release and rate at which calcium ion release reaches maximum were dependent
on ESA (p < 0.05) while maximum calcium ion release was dependent on Vol of TSC
(p < 0.05). Maximum calcium ion release was significantly higher in acidic
solution followed by neutral and alkaline solution (p < 0.05).
PMID- 29342838
TI - Biopolymer-Based Nanoparticles for Cystic Fibrosis Lung Gene Therapy Studies.
AB - Lung gene therapy for cystic fibrosis disease has not been successful due to
several challenges such as the absence of an appropriate vector. Therefore,
optimal delivery of emerging therapeutics to airway epithelial cells demands
suitable non-viral systems. In this work, we describe the formulation and the
physicochemical investigation of biocompatible and biodegradable polymeric
nanoparticles (NPs), including PLGA and chitosan (animal and non-animal), as
novel methods for the safe and efficient delivery of CFTR-specific locked nucleic
acids (LNAs).
PMID- 29342839
TI - Calcium Phosphates as Delivery Systems for Bisphosphonates.
AB - Bisphosphonates (BPs) are the most utilized drugs for the treatment of
osteoporosis, and are usefully employed also for other pathologies characterized
by abnormally high bone resorption, including bone metastases. Due to the great
affinity of these drugs for calcium ions, calcium phosphates are ideal delivery
systems for local administration of BPs to bone, which is aimed to avoid/limit
the undesirable side effects of their prolonged systemic use. Direct synthesis in
aqueous medium and chemisorptions from solution are the two main routes proposed
to synthesize BP functionalized calcium phosphates. The present review overviews
the information acquired through the studies on the interaction between
bisphosphonate molecules and calcium phosphates. Moreover, particular attention
is addressed to some important recent achievements on the applications of BP
functionalized calcium phosphates as biomaterials for bone substitution/repair.
PMID- 29342840
TI - Evaluation of Rapid, Early Warning Approaches to Track Shellfish Toxins
Associated with Dinophysis and Alexandrium Blooms.
AB - Marine biotoxin-contaminated seafood has caused thousands of poisonings worldwide
this century. Given these threats, there is an increasing need for improved
technologies that can be easily integrated into coastal monitoring programs. This
study evaluates approaches for monitoring toxins associated with recurrent toxin
producing Alexandrium and Dinophysis blooms on Long Island, NY, USA, which cause
paralytic and diarrhetic shellfish poisoning (PSP and DSP), respectively. Within
contrasting locations, the dynamics of pelagic Alexandrium and Dinophysis cell
densities, toxins in plankton, and toxins in deployed blue mussels (Mytilus
edulis) were compared with passive solid-phase adsorption toxin tracking (SPATT)
samplers filled with two types of resin, HP20 and XAD-2. Multiple species of wild
shellfish were also collected during Dinophysis blooms and used to compare toxin
content using two different extraction techniques (single dispersive and double
exhaustive) and two different toxin analysis assays (liquid chromatography/mass
spectrometry and the protein phosphatase inhibition assay (PP2A)) for the
measurement of DSP toxins. DSP toxins measured in the HP20 resin were
significantly correlated (R2 = 0.7-0.9, p < 0.001) with total DSP toxins in
shellfish, but were detected more than three weeks prior to detection in deployed
mussels. Both resins adsorbed measurable levels of PSP toxins, but neither
quantitatively tracked Alexandrium cell densities, toxicity in plankton or toxins
in shellfish. DSP extraction and toxin analysis methods did not differ
significantly (p > 0.05), were highly correlated (R2 = 0.98-0.99; p < 0.001) and
provided complete recovery of DSP toxins from standard reference materials. Blue
mussels (Mytilus edulis) and ribbed mussels (Geukensia demissa) were found to
accumulate DSP toxins above federal and international standards (160 ng g-1)
during Dinophysis blooms while Eastern oysters (Crassostrea virginica) and soft
shell clams (Mya arenaria) did not. This study demonstrated that SPATT samplers
using HP20 resin coupled with PP2A technology could be used to provide early
warning of DSP, but not PSP, events for shellfish management.
PMID- 29342842
TI - Investigating Effect of Service Encounter, Value, and Satisfaction on Word of
Mouth: An Outpatient Service Context.
AB - This study investigates the relationships among service encounter, service value,
patient satisfaction, and word-of-mouth (WOM) intention from the viewpoint of
interactive marketing. Data were collected using a questionnaire survey. A total
of 372 questionnaires were obtained and 350 of these questionnaires were valid
(94.09%), and a structural equation model was used to analyze the data. This
study proposed seven hypotheses, and five of the seven hypotheses were supported.
Service encounters indirectly affect their patient WOM through service value and
satisfaction. Therefore, service value and satisfaction play a crucial mediating
role in linking service encounters and WOM. This study determined WOM intentions
in an outpatient service context and provides crucial business implications for
teaching hospitals to enable them to improve their service quality and achieve a
sustainable operation.
PMID- 29342841
TI - miR-3189-3p Mimics Enhance the Effects of S100A4 siRNA on the Inhibition of
Proliferation and Migration of Gastric Cancer Cells by Targeting CFL2.
AB - GDF15 is a downstream gene of S100A4. miR-3189 is embedded in the intron of GDF15
and coexpressed with it. miR-3189-3p functions to inhibit the proliferation and
migration of glioblastoma cells. We speculated that S100A4 might regulate miR
3189-3p to affect its function in gastric cancer cells. Quantitative reverse
transcription polymerase chain reaction (qRT-PCR) showed that miR-3189-3p
expression was significantly downregulated in MGC803 cells after S100A4
knockdown. Overexpression of miR-3189-3p significantly inhibited the
proliferation and migration of the cells. Moreover, miR-3189-3p mimics enhanced
the effects of an S100A4 siRNA on the inhibition of cell proliferation and
migration. Dual luciferase reporter assays, qRT-PCR, and Western blotting
verified that CFL2 is a direct target of miR-3189-3p. CFL2 mediates the
regulation of miR-3189-3p on the proliferation and migration of MGC803 cells.
Data mining based on Kaplan-Meier plots showed that high CFL2 expression is
associated with poor overall survival and first progression in gastric cancer.
These data suggested that miR-3189-3p mimics enhanced the effects of the S100A4
siRNA on the inhibition of gastric cancer cell proliferation and migration by
targeting CFL2. The findings suggested that when targeting S100A4 to treat
gastric cancer, consideration and correction for counteracting factors should
obtain a satisfactory effect.
PMID- 29342843
TI - Chiral and Molecular Recognition through Protonation between Aromatic Amino Acids
and Tripeptides Probed by Collision-Activated Dissociation in the Gas Phase.
AB - Chiral and molecular recognition through protonation was investigated through the
collision-activated dissociation (CAD) of protonated noncovalent complexes of
aromatic amino acid enantiomers with l-alanine- and l-serine-containing
tripeptides using a linear ion trap mass spectrometer. In the case of l-alanine
tripeptide (AAA), NH3 loss was observed in the CAD of heterochiral H+(d-Trp)AAA,
while H2O loss was the main dissociation pathways for l-Trp, d-Phe, and l-Phe.
The protonation site of heterochiral H+(d-Trp)AAA was the amino group of d-Trp,
and the NH3 loss occurred from H+(d-Trp). The H2O loss indicated that the proton
was attached to the l-alanine tripeptide in the noncovalent complexes. With the
substitution of a central residue of l-alanine tripeptide to l-Ser, ASA
recognized l-Phe by protonation to the amino group of l-Phe in homochiral H+(l
Phe)ASA. For the protonated noncovalent complexes of His enantiomers with
tripeptides (AAA, SAA, ASA, and AAS), protonated His was observed in the spectra,
except for those of heterochiral H+(d-His)SAA and H+(d-His)AAS, indicating that d
His did not accept protons from the SAA and AAS in the noncovalent complexes. The
amino-acid sequences of the tripeptides required for the recognition of aromatic
amino acids were determined by analyses of the CAD spectra.
PMID- 29342844
TI - Short Vacation Improves Stress-Level and Well-Being in German-Speaking Middle
Managers-A Randomized Controlled Trial.
AB - Stress in the work place has a detrimental effect on people's health. Sufficient
recovery is necessary to counteract severe chronic negative load reactions.
Previous research has shown that vacationing for at least seven consecutive days
provided an efficient recovery strategy. Yet, thus far, the effects of short
vacations and the mode of vacation (whether at home or in a new environment) have
rarely been studied. We investigated the immediate and long-term effects of a
short vacation (four nights) on well-being and perceived stress and whether the
mode of vacation impacted on these results. Data was obtained from 40 middle
managers (67.5% men and 32.5% women). The intervention group (n = 20) spent a
short vacation in a hotel outside their usual environment. The control group (n =
20) spent their vacation at home. Results indicated that one single short-term
vacation, independent of the mode, has large, positive and immediate effects on
perceived stress, recovery, strain, and well-being. Strain levels decreased to a
greater extent in the intervention group compared to the control group. The
effects can still be detected at 30 days (recovery) and 45 days (well-being and
strain) post-vacation. Encouraging middle management employees to take short
vacations seems to be an efficient health promotion strategy; environmental
effects seem to play a minor role.
PMID- 29342845
TI - Anesthetic Preconditioning as Endogenous Neuroprotection in Glaucoma.
AB - Blindness in glaucoma is the result of death of Retinal Ganglion Cells (RGCs) and
their axons. RGC death is generally preceded by a stage of reversible dysfunction
and structural remodeling. Current treatments aimed at reducing intraocular
pressure (IOP) are ineffective or incompletely effective in management of the
disease. IOP-independent neuroprotection or neuroprotection as adjuvant to IOP
lowering in glaucoma remains a challenge as effective agents without side effects
have not been identified yet. We show in DBA/2J mice with spontaneous IOP
elevation and glaucoma that the lifespan of functional RGCs can be extended by
preconditioning RGCs with retrobulbar lidocaine in one eye at four months of age
that temporary blocks RGC axonal transport. The contralateral, PBS-injected eye
served as control. Lidocaine-induced impairment of axonal transport to superior
colliculi was assessed by intravitreal injection of cholera toxin B. Long-term
(nine months) effect of lidocaine were assessed on RGC electrical responsiveness
(PERG), IOP, expression of relevant protein (BDNF, TrkB, PSD95, GFAP,
Synaptophysin, and GAPDH) and RGC density. While lidocaine treatment did not
alter the age-related increase of IOP, TrkB expression was elevated, GFAP
expression was decreased, RGC survival was improved by 35%, and PERG function was
preserved. Results suggest that the lifespan of functional RGCs in mouse glaucoma
can be extended by preconditioning RGCs in early stages of the disease using a
minimally invasive treatment with retrobulbar lidocaine, a common ophthalmologic
procedure. Lidocaine is inexpensive, safe and is approved by Food and Drug
Administration (FDA) to be administered intravenously.
PMID- 29342846
TI - Mental Health and Drivers of Need in Emergent and Non-Emergent Emergency
Department (ED) Use: Do Living Location and Non-Emergent Care Sources Matter?
AB - Emergency department (ED) utilization has increased due to factors such as
admissions for mental health conditions, including suicide and self-harm. We
investigate direct and moderating influences on non-emergent ED utilization
through the Behavioral Model of Health Services Use. Through logistic regression,
we examined correlates of ED use via 2014 New York State Department of Health
Statewide Planning and Research Cooperative System outpatient data. Consistent
with the primary hypothesis, mental health admissions were associated with
emergent use across models, with only a slight decrease in effect size in rural
living locations. Concerning moderating effects, Spanish/Hispanic origin was
associated with increased likelihood for emergent ED use in the rural living
location model, and non-emergent ED use for the no non-emergent source model.
'Other' ethnic origin increased the likelihood of emergent ED use for rural
living location and no non-emergent source models. The findings reveal 'need',
including mental health admissions, as the largest driver for ED use. This may be
due to mental healthcare access, or patients with mental health emergencies being
transported via first responders to the ED, as in the case of suicide, self-harm,
manic episodes or psychotic episodes. Further educating ED staff on this patient
population through gatekeeper training may ensure patients receive the best
treatment and aid in driving access to mental healthcare delivery changes.
PMID- 29342847
TI - How Work Characteristics Are Related to European Workers' Psychological Well
Being. A Comparison of Two Age Groups.
AB - This study aimed to analyze the mechanisms through which work characteristics are
related to psychological well-being, exploring the mediational role of work
meaningfulness and job satisfaction, and investigating differences in the
patterns of relationships between two age groups. The sample was composed of
36,896 workers from the 5th European Working Conditions Survey. Structural
equation modeling analyses and multiple group analyses were performed. The
results revealed a parallel mediational model, in which work meaningfulness and
general job satisfaction mediate the relationships between work characteristics
and well-being. Additionally, job satisfaction partially mediates the
relationship between meaningfulness and well-being. These results were confirmed
in both age groups (under 55 years old and older workers), but age moderates the
relationships between social support and the mediating variables and the
relationships between the mediating variables and general well-being. The present
study uncovers significant pathways through which time pressure, decision
latitude, and social support are related to psychological well-being, depicting
an important step in better understanding how and when work characteristics are
related to positive outcomes. It provides important clues for promoting
psychosocial health at work at the European level.
PMID- 29342848
TI - A Voltammetric Electronic Tongue for the Resolution of Ternary Nitrophenol
Mixtures.
AB - This work reports the applicability of a voltammetric sensor array able to
quantify the content of 2,4-dinitrophenol, 4-nitrophenol, and picric acid in
artificial samples using the electronic tongue (ET) principles. The ET is based
on cyclic voltammetry signals, obtained from an array of metal disk electrodes
and a graphite epoxy composite electrode, compressed using discrete wavelet
transform with chemometric tools such as artificial neural networks (ANNs). ANNs
were employed to build the quantitative prediction model. In this manner, a set
of standards based on a full factorial design, ranging from 0 to 300 mg.L-1, was
prepared to build the model; afterward, the model was validated with a completely
independent set of standards. The model successfully predicted the concentration
of the three considered phenols with a normalized root mean square error of 0.030
and 0.076 for the training and test subsets, respectively, and r >= 0.948.
PMID- 29342849
TI - Comparative Response of the Hepatic Transcriptomes of Domesticated and Wild
Turkey to Aflatoxin B1.
AB - The food-borne mycotoxin aflatoxin B1 (AFB1) poses a significant risk to poultry,
which are highly susceptible to its hepatotoxic effects. Domesticated turkeys
(Meleagris gallopavo) are especially sensitive, whereas wild turkeys (M. g.
silvestris) are more resistant. AFB1 toxicity entails bioactivation by hepatic
cytochrome P450s to the electrophilic exo-AFB1-8,9-epoxide (AFBO). Domesticated
turkeys lack functional hepatic GST-mediated detoxification of AFBO, and this is
largely responsible for the differences in resistance between turkey types. This
study was designed to characterize transcriptional changes induced in turkey
livers by AFB1, and to contrast the response of domesticated (susceptible) and
wild (more resistant) birds. Gene expression responses to AFB1 were examined
using RNA-sequencing. Statistically significant differences in gene expression
were observed among treatment groups and between turkey types. Expression
analysis identified 4621 genes with significant differential expression (DE) in
AFB1-treated birds compared to controls. Characterization of DE transcripts
revealed genes dis-regulated in response to toxic insult with significant
association of Phase I and Phase II genes and others important in cellular
regulation, modulation of apoptosis, and inflammatory responses. Constitutive
expression of GSTA3 was significantly higher in wild birds and was significantly
higher in AFB1-treated birds when compared to controls for both genetic groups.
This pattern was also observed by qRT-PCR in other wild and domesticated turkey
strains. Results of this study emphasize the differential response of these
genetically distinct birds, and identify genes and pathways that are
differentially altered in aflatoxicosis.
PMID- 29342850
TI - Multi-Sensor Based Online Attitude Estimation and Stability Measurement of
Articulated Heavy Vehicles.
AB - Articulated wheel loaders used in the construction industry are heavy vehicles
and have poor stability and a high rate of accidents because of the unpredictable
changes of their body posture, mass and centroid position in complex operation
environments. This paper presents a novel distributed multi-sensor system for
real-time attitude estimation and stability measurement of articulated wheel
loaders to improve their safety and stability. Four attitude and heading
reference systems (AHRS) are constructed using micro-electro-mechanical system
(MEMS) sensors, and installed on the front body, rear body, rear axis and boom of
an articulated wheel loader to detect its attitude. A complementary filtering
algorithm is deployed for sensor data fusion in the system so that steady state
margin angle (SSMA) can be measured in real time and used as the judge index of
rollover stability. Experiments are conducted on a prototype wheel loader, and
results show that the proposed multi-sensor system is able to detect potential
unstable states of an articulated wheel loader in real-time and with high
accuracy.
PMID- 29342851
TI - Laser Machining and In Vitro Assessment of Wollastonite-Tricalcium Phosphate
Eutectic Glasses and Glass-Ceramics.
AB - Bioactivity and ingrowth of ceramic implants is commonly enhanced by a suitable
interconnected porous network. In this work, the laser machining of CaSiO3
Ca3(PO4)2 biocompatible eutectic glass-ceramics and glasses was studied. For this
purpose, 300 um diameter craters were machined by using pulsed laser radiation at
532 nm with a pulsewidth in the nanosecond range. Machined samples were soaked in
simulated body fluid for 2 months to assess the formation of a hydroxyapatite
layer on the surface of the laser machined areas. The samples were manufactured
by the laser floating zone technique using a CO2 laser. Morphology, composition
and microstructure of the machined samples were described by Field Emission
Scanning Electron Microscopy, Energy Dispersive X-ray Spectroscopy and micro
Raman Spectroscopy.
PMID- 29342852
TI - Atmospheric Environment Vulnerability Cause Analysis for the Beijing-Tianjin
Hebei Metropolitan Region.
AB - Assessing and quantifying atmospheric vulnerability is a key issue in urban
environmental protection and management. This paper integrated the Analytical
hierarchy process (AHP), fuzzy synthesis evaluation and Geographic Information
System (GIS) spatial analysis into an Exposure-Sensitivity-Adaptive capacity
(ESA) framework to quantitatively assess atmospheric environment vulnerability in
the Beijing-Tianjin-Hebei (BTH) region with spatial and temporal comparisons. The
elaboration of the relationships between atmospheric environment vulnerability
and indices of exposure, sensitivity, and adaptive capacity supports enable
analysis of the atmospheric environment vulnerability. Our findings indicate that
the atmospheric environment vulnerability of 13 cities in the BTH region exhibits
obvious spatial heterogeneity, which is caused by regional diversity in exposure,
sensitivity, and adaptive capacity indices. The results of atmospheric
environment vulnerability assessment and the cause analysis can provide guidance
to pick out key control regions and recognize vulnerable indicators for study
sites. The framework developed in this paper can also be replicated at different
spatial and temporal scales using context-specific datasets to support
environmental management.
PMID- 29342853
TI - Structural Examination of Halogen-Bonded Co-Crystals of Tritopic Acceptors.
AB - A series of tritopic N-heterocyclic compounds containing electrostatically and
geometrically equivalent binding sites were synthesized and subjected to
systematic co-crystallizations with selected perfluoroiodoarenes in order to map
out their structural landscapes. More than 70% of the attempted reactions
produced a co-crystal as indicated by IR spectroscopy. Four new crystal
structures are reported and in all of them, at least one potential binding site
on the acceptor is left vacant. The absence of halogen bonds to all sites can be
ascribed primarily due to deactivation of the sigma-hole on the iodo-arene donors
and partially due to steric hindrance. The tritopic acceptors containing 5,6
dimethylbenzimidazole derivatives yield discrete tetrameric aggregates in the
solid state, whereas the pyrazole and imidazole analogues assemble into halogen
bonded 1-D chains.
PMID- 29342854
TI - Impact of Prolonged Blood Incubation and Extended Serum Storage at Room
Temperature on the Human Serum Metabolome.
AB - Metabolomics is a powerful technology with broad applications in life science
that, like other -omics approaches, requires high-quality samples to achieve
reliable results and ensure reproducibility. Therefore, along with quality
assurance, methods to assess sample quality regarding pre-analytical confounders
are urgently needed. In this study, we analyzed the response of the human serum
metabolome to pre-analytical variations comprising prolonged blood incubation and
extended serum storage at room temperature by using gas chromatography-mass
spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC
MS/MS) -based metabolomics. We found that the prolonged incubation of blood
results in a statistically significant 20% increase and 4% decrease of 225 tested
serum metabolites. Extended serum storage affected 21% of the analyzed
metabolites (14% increased, 7% decreased). Amino acids and nucleobases showed the
highest percentage of changed metabolites in both confounding conditions, whereas
lipids were remarkably stable. Interestingly, the amounts of taurine and O
phosphoethanolamine, which have both been discussed as biomarkers for various
diseases, were 1.8- and 2.9-fold increased after 6 h of blood incubation. Since
we found that both are more stable in ethylenediaminetetraacetic acid (EDTA)
blood, EDTA plasma should be the preferred metabolomics matrix.
PMID- 29342855
TI - Introduction to State Estimation of High-Rate System Dynamics.
AB - Engineering systems experiencing high-rate dynamic events, including airbags,
debris detection, and active blast protection systems, could benefit from real
time observability for enhanced performance. However, the task of high-rate state
estimation is challenging, in particular for real-time applications where the
rate of the observer's convergence needs to be in the microsecond range. This
paper identifies the challenges of state estimation of high-rate systems and
discusses the fundamental characteristics of high-rate systems. A survey of
applications and methods for estimators that have the potential to produce
accurate estimations for a complex system experiencing highly dynamic events is
presented. It is argued that adaptive observers are important to this research.
In particular, adaptive data-driven observers are advantageous due to their
adaptability and lack of dependence on the system model.
PMID- 29342856
TI - Calculation and Identification of the Aerodynamic Parameters for Small-Scaled
Fixed-Wing UAVs.
AB - The establishment of the Aircraft Dynamic Model(ADM) constitutes the prerequisite
for the design of the navigation and control system, but the aerodynamic
parameters in the model could not be readily obtained especially for small-scaled
fixed-wing UAVs. In this paper, the procedure of computing the aerodynamic
parameters is developed. All the longitudinal and lateral aerodynamic derivatives
are firstly calculated through semi-empirical method based on the aerodynamics,
rather than the wind tunnel tests or fluid dynamics software analysis. Secondly,
the residuals of each derivative are proposed to be identified or estimated
further via Extended Kalman Filter(EKF), with the observations of the attitude
and velocity from the airborne integrated navigation system. Meanwhile, the
observability of the targeted parameters is analyzed and strengthened through
multiple maneuvers. Based on a small-scaled fixed-wing aircraft driven by
propeller, the airborne sensors are chosen and the model of the actuators are
constructed. Then, real flight tests are implemented to verify the calculation
and identification process. Test results tell the rationality of the semi
empirical method and show the improvement of accuracy of ADM after the
compensation of the parameters.
PMID- 29342857
TI - An Adaptive Deghosting Method in Neural Network-Based Infrared Detectors
Nonuniformity Correction.
AB - The problems of the neural network-based nonuniformity correction algorithm for
infrared focal plane arrays mainly concern slow convergence speed and ghosting
artifacts. In general, the more stringent the inhibition of ghosting, the slower
the convergence speed. The factors that affect these two problems are the
estimated desired image and the learning rate. In this paper, we propose a
learning rate rule that combines adaptive threshold edge detection and a temporal
gate. Through the noise estimation algorithm, the adaptive spatial threshold is
related to the residual nonuniformity noise in the corrected image. The proposed
learning rate is used to effectively and stably suppress ghosting artifacts
without slowing down the convergence speed. The performance of the proposed
technique was thoroughly studied with infrared image sequences with both
simulated nonuniformity and real nonuniformity. The results show that the
deghosting performance of the proposed method is superior to that of other neural
network-based nonuniformity correction algorithms and that the convergence speed
is equivalent to the tested deghosting methods.
PMID- 29342858
TI - Novel Fiber-Optic Ring Acoustic Emission Sensor.
AB - Acoustic emission technology has been applied to many fields for many years.
However, the conventional piezoelectric acoustic emission sensors cannot be used
in extreme environments, such as those with heavy electromagnetic interference,
high pressure, or strong corrosion. In this paper, a novel fiber-optic ring
acoustic emission sensor is proposed. The sensor exhibits high sensitivity, anti
electromagnetic interference, and corrosion resistance. First, the principle of a
novel fiber-optic ring sensor is introduced. Different from piezoelectric and
other fiber acoustic emission sensors, this novel sensor includes both a sensing
skeleton and a sensing fiber. Second, a heterodyne interferometric demodulating
method is presented. In addition, a fiber-optic ring sensor acoustic emission
system is built based on this method. Finally, fiber-optic ring acoustic emission
experiments are performed. The novel fiber-optic ring sensor is glued onto the
surface of an aluminum plate. The 150 kHz standard continuous sinusoidal signals
and broken lead signals are successfully detected by the novel fiber-optic ring
acoustic emission sensor. In addition, comparison to the piezoelectric acoustic
emission sensor is performed, which shows the availability and reliability of the
novel fiber-optic ring acoustic emission sensor. In the future, this novel fiber
optic ring acoustic emission sensor will provide a new route to acoustic emission
detection in harsh environments.
PMID- 29342859
TI - Multinuclear NMR Measurements and DFT Calculations for Capecitabine Tautomeric
Form Assignment in a Solution.
AB - The molecular structure of capecitabine (a widely applied prodrug of 5
fluorouracil) was studied by multinuclear NMR measurements and DFT quantum
mechanical calculations. One or two tautomeric forms in a solution were detected
depending on the solvent used. In the organic solvents, a mixture of two forms of
capecitabine was observed: carbamate and imine tautomers. In the aqueous
solution, only the carbamate form was found. The methylation of capecitabine
yields mainly two products in different proportions: N3-methylcapecitabine and N7
methylcapecitabine. The protonation of capecitabine in organic solvents with
perchloric acid occurs at the N3 nitrogen atom. DFT calculations strongly support
the results coming from the analysis of the NMR spectra.
PMID- 29342860
TI - AuNPs Hybrid Black ZnO Nanorods Made by a Sol-Gel Method for Highly Sensitive
Humidity Sensing.
AB - A highly sensitive self-powered humidity sensor has been realized from AuNPs
hybrid black zinc oxide (ZnO) nanorods prepared through a sol-gel method. XRD
pattern reveals that both ZnO and ZnO/AuNPs exhibit a wurtzite structure.
ZnO/AuNPs nanorods grow in a vertical alignment, which possesses high uniformity
and forms dense arrays with a smaller diameter than that of ZnO nanoparticles.
All ZnO/AuNPs and pure black ZnO show lower band gap energy than the typically
reported 3.34 eV of pure ZnO. Furthermore, the band gap of ZnO/AuNPs
nanocomposites is effectively influenced by the amount of AuNPs. The humidity
sensing tests clearly prove that all the ZnO/AuNPs humidity sensors exhibit much
higher response than that of ZnO sensors, and the sensitivity of such ZnO/AuNPs
nanorods (6 mL AuNPs) display a change three orders higher than that of pure ZnO
with relative humidity (RH) ranging from 11% to 95% at room temperature. The
response and recovery time of the ZnO/AuNPs are 5.6 s and 32.4 s, respectively.
This study of the construction of semiconductor/noble metal sensors provides a
rational way to control the morphology of semiconductor nanomaterials and to
design a humidity sensor with high performance.
PMID- 29342862
TI - Heterogeneous Contributing Factors in MPM Disease Development and Progression:
Biological Advances and Clinical Implications.
AB - Malignant pleural mesothelioma (MPM) tumors are remarkably aggressive and most
patients only survive for 5-12 months; irrespective of stage; after primary
symptoms appear. Compounding matters is that MPM remains unresponsive to
conventional standards of care; including radiation and chemotherapy. Currently;
instead of relying on molecular signatures and histological typing; MPM treatment
options are guided by clinical stage and patient characteristics because the
mechanism of carcinogenesis has not been fully elucidated; although about 80% of
cases can be linked to asbestos exposure. Several molecular pathways have been
implicated in the MPM tumor microenvironment; such as angiogenesis; apoptosis;
cell-cycle regulation and several growth factor-related pathways predicted to be
amenable to therapeutic intervention. Furthermore, the availability of genomic
data has improved our understanding of the pathobiology of MPM. The MPM genomic
landscape is dominated by inactivating mutations in several tumor suppressor
genes; such as CDKN2A; BAP1 and NF2. Given the complex heterogeneity of the tumor
microenvironment in MPM; a better understanding of the interplay between stromal;
endothelial and immune cells at the molecular level is required; to chaperone the
development of improved personalized therapeutics. Many recent advances at the
molecular level have been reported and several exciting new treatment options are
under investigation. Here; we review the challenges and the most up-to-date
biological advances in MPM pertaining to the molecular pathways implicated;
progress at the genomic level; immunological progression of this fatal disease;
and its link with developmental cell pathways; with an emphasis on prognostic and
therapeutic treatment strategies.
PMID- 29342863
TI - Validation of a Rapid Method to Assess Habitual Beverage Intake Patterns.
AB - The Healthy Beverage Index (HBI) is an emerging approach to assess beverage
pattern quality. HBI total scores range from 0 to 100, with higher scores
indicating greater adherence to proposed beverage recommendations. However,
assessing patterns is resource-intensive due to the need for extensive dietary
data, typically 24-h dietary records or recalls. The BEVQ-15, a beverage intake
questionnaire, may be used as an alternative method to rapidly measure HBI
scores. The objective of this cross-sectional investigation is to assess the
comparative validity of the HBI-Q, a method to rapidly assess HBI scores via the
BEVQ-15, as compared to the traditional method of deriving HBI scores via dietary
recalls/records. Between 2012 and 2016, a cross-sectional sample of adults in
southwest Virginia completed three 24-h dietary recalls (30-60 min administration
and analysis time per recall) and the BEVQ-15 (3-4 min administration time). HBI
scores were generated by both methods, and compared via paired-samples t-tests,
correlations, and Bland-Altman analysis. Among 404 adults (mean age = 40 years),
total mean HBI scores were 63.7 from the HBI-Q and 67.3 from the recalls (mean
difference = 3.6 out of 100; r = 0.63; both p <= 0.001). Agreement between the
two methods for total HBI scores via Bland-Altman plots was 92%. Using the HBI-Q
to rapidly assess HBI scores in adults will increase the utility of the HBI by
decreasing the time and resources required, thus allowing researchers and
practitioners to provide targeted feedback for improvement.
PMID- 29342861
TI - Rational Management of Iron-Deficiency Anaemia in Inflammatory Bowel Disease.
AB - Anaemia is the most frequent, though often neglected, comorbidity of inflammatory
bowel disease (IBD). Here we want to briefly present (1) the burden of anaemia in
IBD, (2) its pathophysiology, which mostly arises from bleeding-associated iron
deficiency, followed by (3) diagnostic evaluation of anaemia, (4) a balanced
overview of the different modes of iron replacement therapy, (5) evidence for
their therapeutic efficacy and subsequently, (6) an updated recommendation for
the practical management of anaemia in IBD. Following the introduction of various
intravenous iron preparations over the last decade, questions persist about when
to use these preparations as opposed to traditional and other novel oral iron
therapeutic agents. At present, oral iron therapy is generally preferred for
patients with quiescent IBD and mild iron-deficiency anaemia. However, in
patients with flaring IBD that hampers intestinal iron absorption and in those
with inadequate responses to or side effects with oral preparations, intravenous
iron supplementation is the therapy of choice, although information on the
efficacy of intravenous iron in patients with active IBD and anaemia is scare.
Importantly, anaemia in IBD is often multifactorial and a careful diagnostic
workup is mandatory for optimized treatment. Nevertheless, limited information is
available on optimal therapeutic start and end points for treatment of anaemia.
Of note, neither oral nor intravenous therapies seem to exacerbate the clinical
course of IBD. However, additional prospective studies are still warranted to
determine the optimal therapy in complex conditions such as IBD.
PMID- 29342864
TI - Mechanical Properties of a Newly Additive Manufactured Implant Material Based on
Ti-42Nb.
AB - The application of Ti-6Al-4V alloy or commercially pure titanium for additive
manufacturing enables the fabrication of complex structural implants and patient
specific implant geometries. However, the difference in Young's modulus of alpha
+ beta-phase Ti alloys compared to the human bone promotes stress-shielding
effects in the implant-bone interphase. The aim of the present study is the
mechanical characterization of a new pre-alloyed beta-phase Ti-42Nb alloy for
application in additive manufacturing. The present investigation focuses on the
mechanical properties of SLM-printed Ti-42Nb alloy in tensile and compression
tests. In addition, the raw Ti-42Nb powder, the microstructure of the specimens
prior to and after compression tests, as well as the fracture occurring in
tensile tests are characterized by means of the SEM/EDX analysis. The Ti-42Nb raw
powder exhibits a dendrite-like Ti-structure, which is melted layer-by-layer into
a microstructure with a very homogeneous distribution of Nb and Ti during the SLM
process. Tensile tests display Young's modulus of 60.51 +/- 3.92 GPa and an
ultimate tensile strength of 683.17 +/- 16.67 MPa, whereas, under a compressive
load, a compressive strength of 1330.74 +/- 53.45 MPa is observed. The
combination of high mechanical strength and low elastic modulus makes Ti-42Nb an
interesting material for orthopedic and dental implants. The spherical shape of
the pre-alloyed material additionally allows for application in metal 3D
printing, enabling the fabrication of patient-specific structural implants.
PMID- 29342865
TI - Acute Post-Prandial Cognitive Effects of Brown Seaweed Extract in Humans.
AB - (Poly)phenols and, specifically, phlorotannins present in brown seaweeds have
previously been shown to inhibit alpha-amylase and alpha-glucosidase, key enzymes
involved in the breakdown and intestinal absorption of carbohydrates. Related to
this are observations of modulation of post-prandial glycemic response in mice
and increased insulin sensitivity in humans when supplemented with seaweed
extract. However, no studies to date have explored the effect of seaweed extract
on cognition. The current randomized, placebo-controlled, double-blind, parallel
groups study examined the impact of a brown seaweed extract on cognitive function
post-prandially in 60 healthy adults (N = 30 per group). Computerized measures of
episodic memory, attention and subjective state were completed at baseline and 5
times at 40 min intervals over a 3 h period following lunch, with either seaweed
or placebo consumed 30 min prior to lunch. Analysis was conducted with linear
mixed models controlling for baseline. Seaweed led to significant improvements to
accuracy on digit vigilance (p = 0.035) and choice reaction time (p = 0.043)
tasks. These findings provide the first evidence for modulation of cognition with
seaweed extract. In order to explore the mechanism underlying these effects,
future research should examine effects on cognition in parallel with blood
glucose and insulin responses.
PMID- 29342866
TI - Guanidinoacetic Acid and Creatine are Associated with Cardiometabolic Risk
Factors in Healthy Men and Women: A Cross-Sectional Study.
AB - Guanidinoacetic acid (GAA) conversion to creatine is thought to be involved in
cardiometabolic disturbances through its role in biological methylation and
insulin secretion. We evaluated the association of serum GAA and creatine with
cardiometabolic risk factors in a cohort of 151 apparently healthy adults (82
women and 69 men) aged 18-63 years. Serum levels of GAA and creatine were
measured with liquid chromatography-tandem mass spectrometry. A multiple linear
regression model adjusted for age and sex was employed to examine the
relationship of serum GAA and creatine with cardiometabolic risk factors. Higher
GAA levels were associated with an unfavorable cardiometabolic risk profile
(higher insulin, higher total homocysteine, and higher body fat percentage),
while having elevated serum creatine levels (>=31.1 umol/L) was associated with
being overweight (body mass index >= 25.0 kg/m). The results from our study
suggest a possible role of the GAA-creatine axis in the pathogenesis of
cardiovascular and metabolic diseases.
PMID- 29342867
TI - A Longitudinal Study of 25-Hydroxy Vitamin D and Parathyroid Hormone Status
throughout Pregnancy and Exclusive Lactation in New Zealand Mothers and Their
Infants at 45 degrees S.
AB - Vitamin D status and associated metabolism during pregnancy and lactation have
been assessed in only a limited number of longitudinal studies, all from the
northern hemisphere, with no infant data concurrently reported. Therefore, we
aimed to describe longitudinal maternal and infant 25-hydroxy vitamin D (25OHD)
and parathyroid hormone (PTH) status during pregnancy and up to 5 months
postnatal age, in New Zealand women and their infants living at 45 degrees S
latitude. Between September 2011 and June 2013, 126 pregnant women intending to
exclusively breastfeed for at least 20 weeks were recruited. Longitudinal data
were collected at three time-points spanning pregnancy, and following birth and
at 20 weeks postpartum. Vitamin D deficiency (25OHD < 50 nmol/L) was common,
found at one or more time-points in 65% and 76% of mothers and their infants,
respectively. Mean cord 25OHD was 41 nmol/L, and three infants exhibited
secondary hyperparathyroidism by postnatal week 20. Maternal late pregnancy 25OHD
(gestation 32-38 weeks) was closely correlated with infant cord 25OHD, r2 = 0.87
(95% CI (Confidence interval) 0.8-0.91), while no correlation was seen between
early pregnancy (<20 weeks gestation) maternal and cord 25OHD, r2 = 0.06 (95% CI
0.16-0.28). Among other variables, pregnancy 25OHD status, and therefore infant
status at birth, were influenced by season of conception. In conclusion, vitamin
D deficiency in women and their infants is very common during pregnancy and
lactation in New Zealand at 45 degrees S. These data raise questions regarding
the applicability of current pregnancy and lactation policy at this latitude,
particularly recommendations relating to first trimester maternal vitamin D
screening and targeted supplementation for those "at risk".
PMID- 29342869
TI - Surface Fitting for Quasi Scattered Data from Coordinate Measuring Systems.
AB - Non-uniform rational B-spline (NURBS) surface fitting from data points is wildly
used in the fields of computer aided design (CAD), medical imaging, cultural
relic representation and object-shape detection. Usually, the measured data
acquired from coordinate measuring systems is neither gridded nor completely
scattered. The distribution of this kind of data is scattered in physical space,
but the data points are stored in a way consistent with the order of measurement,
so it is named quasi scattered data in this paper. Therefore they can be
organized into rows easily but the number of points in each row is random. In
order to overcome the difficulty of surface fitting from this kind of data, a new
method based on resampling is proposed. It consists of three major steps: (1)
NURBS curve fitting for each row, (2) resampling on the fitted curve and (3)
surface fitting from the resampled data. Iterative projection optimization scheme
is applied in the first and third step to yield advisable parameterization and
reduce the time cost of projection. A resampling approach based on parameters,
local peaks and contour curvature is proposed to overcome the problems of nodes
redundancy and high time consumption in the fitting of this kind of scattered
data. Numerical experiments are conducted with both simulation and practical
data, and the results show that the proposed method is fast, effective and
robust. What's more, by analyzing the fitting results acquired form data with
different degrees of scatterness it can be demonstrated that the error introduced
by resampling is negligible and therefore it is feasible.
PMID- 29342868
TI - Hypoxia and Hormone-Mediated Pathways Converge at the Histone Demethylase KDM4B
in Cancer.
AB - Hormones play an important role in pathophysiology. The hormone receptors, such
as estrogen receptor alpha and androgen receptor in breast cancer and prostate
cancer, are critical to cancer cell proliferation and tumor growth. In this
review we focused on the cross-talk between hormone and hypoxia pathways,
particularly in breast cancer. We delineated a novel signaling pathway from
estrogen receptor to hypoxia-inducible factor 1, and discussed the role of this
pathway in endocrine therapy resistance. Further, we discussed the estrogen and
hypoxia pathways converging at histone demethylase KDM4B, an important epigenetic
modifier in cancer.
PMID- 29342870
TI - Biomarkers of Progression after HIV Acute/Early Infection: Nothing Compares to
CD4+ T-cell Count?
AB - Progression of HIV infection is variable among individuals, and definition
disease progression biomarkers is still needed. Here, we aimed to categorize the
predictive potential of several variables using feature selection methods and
decision trees. A total of seventy-five treatment-naive subjects were enrolled
during acute/early HIV infection. CD4+ T-cell counts (CD4TC) and viral load (VL)
levels were determined at enrollment and for one year. Immune activation, HIV
specific immune response, Human Leukocyte Antigen (HLA) and C-C chemokine
receptor type 5 (CCR5) genotypes, and plasma levels of 39 cytokines were
determined. Data were analyzed by machine learning and non-parametric methods.
Variable hierarchization was performed by Weka correlation-based feature
selection and J48 decision tree. Plasma interleukin (IL)-10, interferon gamma
induced protein (IP)-10, soluble IL-2 receptor alpha (sIL-2Ralpha) and tumor
necrosis factor alpha (TNF-alpha) levels correlated directly with baseline VL,
whereas IL-2, TNF-alpha, fibroblast growth factor (FGF)-2 and macrophage
inflammatory protein (MIP)-1beta correlated directly with CD4+ T-cell activation
(p < 0.05). However, none of these cytokines had good predictive values to
distinguish "progressors" from "non-progressors". Similarly, immune activation,
HIV-specific immune responses and HLA/CCR5 genotypes had low discrimination
power. Baseline CD4TC was the most potent discerning variable with a cut-off of
438 cells/MUL (accuracy = 0.93, kappa-Cohen = 0.85). Limited discerning power of
the other factors might be related to frequency, variability and/or sampling
time. Future studies based on decision trees to identify biomarkers of post
treatment control are warrantied.
PMID- 29342872
TI - Human Cytomegalovirus Nuclear Capsids Associate with the Core Nuclear Egress
Complex and the Viral Protein Kinase pUL97.
AB - The nuclear phase of herpesvirus replication is regulated through the formation
of regulatory multi-component protein complexes. Viral genomic replication is
followed by nuclear capsid assembly, DNA encapsidation and nuclear egress. The
latter has been studied intensely pointing to the formation of a viral core
nuclear egress complex (NEC) that recruits a multimeric assembly of viral and
cellular factors for the reorganization of the nuclear envelope. To date, the
mechanism of the association of human cytomegalovirus (HCMV) capsids with the
NEC, which in turn initiates the specific steps of nuclear capsid budding,
remains undefined. Here, we provide electron microscopy-based data demonstrating
the association of both nuclear capsids and NEC proteins at nuclear lamina
budding sites. Specifically, immunogold labelling of the core NEC constituent
pUL53 and NEC-associated viral kinase pUL97 suggested an intranuclear NEC-capsid
interaction. Staining patterns with phospho-specific lamin A/C antibodies are
compatible with earlier postulates of targeted capsid egress at lamina-depleted
areas. Important data were provided by co-immunoprecipitation and in vitro kinase
analyses using lysates from HCMV-infected cells, nuclear fractions, or infectious
virions. Data strongly suggest that nuclear capsids interact with pUL53 and
pUL97. Combined, the findings support a refined concept of HCMV nuclear
trafficking and NEC-capsid interaction.
PMID- 29342871
TI - Interferons: Reprogramming the Metabolic Network against Viral Infection.
AB - Viruses exploit the host and induce drastic metabolic changes to ensure an
optimal environment for replication and the production of viral progenies. In
response, the host has developed diverse countermeasures to sense and limit these
alterations to combat viral infection. One such host mechanism is through
interferon signaling. Interferons are cytokines that enhances the transcription
of hundreds of interferon-stimulated genes (ISGs) whose products are key players
in the innate immune response to viral infection. In addition to their direct
targeting of viral components, interferons and ISGs exert profound effects on
cellular metabolism. Recent studies have started to illuminate on the specific
role of interferon in rewiring cellular metabolism to activate immune cells and
limit viral infection. This review reflects on our current understanding of the
complex networking that occurs between the virus and host at the interface of
cellular metabolism, with a focus on the ISGs in particular, cholesterol-25
hydroxylase (CH25H), spermidine/spermine acetyltransferase 1 (SAT1), indoleamine
2,3-dioxygenase (IDO1) and sterile alpha motif and histidine/aspartic acid domain
containing protein 1 (SAMHD1), which were recently discovered to modulate
specific metabolic events and consequently deter viral infection.
PMID- 29342873
TI - Association between the Frequency of Protein-Rich Food Intakes and Kihon
Checklist Frailty Indices in Older Japanese Adults: The Kyoto-Kameoka Study.
AB - We aimed to investigate whether frequencies of protein-rich food intake were
associated with frailty among older Japanese adults. A cross-sectional study was
conducted in 2011 among 3843 men and 4331 women in a population-based cohort of
Kameoka city, Kyoto Prefecture, Japan. Frailty was assessed by the weighted score
based on the 25-item Kihon-Checklist. The frequency of protein-rich food intake
was examined as "seafood", "meat", "dairy products", "eggs", and "soy products".
The outcome of frailty was analyzed with a multiple logistic regression model
using the frequency of protein-rich food intake. When compared to the first
quartile, it was observed that there was a significant association between the
lower adjusted prevalence ratio (PR) for frailty and the frequency of seafood
intake in the fourth quartile among men (PR 0.64, 95% confidence interval (CI),
0.42, 0.99) and from the second quartile to the third quartile among women (PR
0.61, 95% CI, 0.43, 0.85; PR 0.64, 95% CI, 0.46, 0.91). The frequency of dairy
products intake in the third quartile among women was significantly associated
with a lower PR for frailty (p-value = 0.013). Our findings suggest that the
consumption of seafood and dairy products may help older adults in maintaining
their independence.
PMID- 29342875
TI - The Detection of Burn-Through Weld Defects Using Noncontact Ultrasonics.
AB - Nearly all manufactured products in the metal industry involve welding. The
detection and correction of defects during welding improve the product
reliability and quality, and prevent unexpected failures. Nonintrusive process
control is critical for avoiding these defects. This paper investigates the
detection of burn-through damage using noncontact, air-coupled ultrasonics, which
can be adapted to the immediate and in-situ inspection of welded samples. The
burn-through leads to a larger volume of degraded weld zone, providing a
resistance path for the wave to travel which results in lower velocity, energy
ratio, and amplitude. Wave energy dispersion occurs due to the increase of weld
burn-through resulting in higher wave attenuation. Weld sample micrographs are
used to validate the ultrasonic results.
PMID- 29342874
TI - Rodent Models of Alcoholic Liver Disease: Role of Binge Ethanol Administration.
AB - Both chronic and acute (binge) alcohol drinking are important health and economic
concerns worldwide and prominent risk factors for the development of alcoholic
liver disease (ALD). There are no FDA-approved medications to prevent or to treat
any stage of ALD. Therefore, discovery of novel therapeutic strategies remains a
critical need for patients with ALD. Relevant experimental animal models that
simulate human drinking patterns and mimic the spectrum and severity of alcohol
induced liver pathology in humans are critical to our ability to identify new
mechanisms and therapeutic targets. There are several animal models currently in
use, including the most widely utilized chronic ad libitum ethanol (EtOH) feeding
(Lieber-DeCarli liquid diet model), chronic intragastric EtOH administration
(Tsukamoto-French model), and chronic-plus-binge EtOH challenge (Bin Gao-National
Institute on Alcohol Abuse and Alcoholism (NIAAA) model). This review provides an
overview of recent advances in rodent models of binge EtOH administration which
help to recapitulate different features and etiologies of progressive ALD. These
models include EtOH binge alone, and EtOH binge coupled with chronic EtOH intake,
a high fat diet, or endotoxin challenge. We analyze the strengths, limitations,
and translational relevance of these models, as well as summarize the liver
injury outcomes and mechanistic insights. We further discuss the application(s)
of binge EtOH models in examining alcohol-induced multi-organ pathology, sex- and
age-related differences, as well as circadian rhythm disruption.
PMID- 29342876
TI - Improvement of Verticillium Wilt Resistance by Applying Arbuscular Mycorrhizal
Fungi to a Cotton Variety with High Symbiotic Efficiency under Field Conditions.
AB - Arbuscular mycorrhizal fungi (AMF) play an important role in nutrient cycling
processes and plant stress resistance. To evaluate the effect of Rhizophagus
irregularis CD1 on plant growth promotion (PGP) and Verticillium wilt disease,
the symbiotic efficiency of AMF (SEA) was first investigated over a range of 3%
to 94% in 17 cotton varieties. The high-SEA subgroup had significant PGP effects
in a greenhouse. From these results, the highest-SEA variety of Lumian 1 was
selected for a two-year field assay. Consistent with the performance from the
greenhouse, the AMF-mediated PGP of Lumian 1 also produced significant results,
including an increased plant height, stem diameter, number of petioles, and
phosphorus content. Compared with the mock treatment, AMF colonization obviously
inhibited the symptom development of Verticillium dahliae and more strongly
elevated the expression of pathogenesis-related genes and lignin synthesis
related genes. These results suggest that AMF colonization could lead to the
mycorrhiza-induced resistance (MIR) of Lumian 1 to V. dahliae. Interestingly, our
results indicated that the AMF endosymbiont could directly inhibit the growth of
phytopathogenic fungi including V. dahliae by releasing undefined volatiles. In
summary, our results suggest that stronger effects of AMF application result from
the high-SEA.
PMID- 29342877
TI - Accumulation of Heavy Metals in Tea Leaves and Potential Health Risk Assessment:
A Case Study from Puan County, Guizhou Province, China.
AB - This study features a survey of the concentrations of aluminum (Al) and heavy
metals (Mn, Pb, Cd, Hg, As, Cr, Ni, Cu, and Zn) in tea leaves and the
corresponding cultivation soils (0-30 cm), carried out in Puan County (Guizhou
Province, China). The average concentrations of Al, Mn, Pb, Cd, Hg, As, Cr, Ni,
Cu, and Zn in the soil were 106 * 103, 214, 20.9, 0.09, 0.12, 17.5, 121, 27.8,
131.2, and 64 mg.kg-1, respectively. The heavy metals' pollution indexes in the
soil can be ranked as follows: Cu > Cr > Hg > As > Ni > Zn > Pb > Mn > Cd. The
soil was moderately polluted by Cu because of the high geochemical background
value of Cu in the area. The potential environment risk index (RI) showed that
7.69% out of the total sample sites were within the moderate level. Moreover, the
ranges of Al, Mn, Pb, Cd, Hg, As, Cr, Ni, Cu, and Zn concentrations in young tea
leaves were 250-660, 194-1130, 0.107-0.400, 0.012-0.092, 0.014-0.085, 0.073
0.456, 0.33-1.26, 6.33-14.90, 14.90-26.10, and 35.8-50.3 mg.kg-1, respectively.
While in mature tea leaves, they were 4300-10,400, 536-4610, 0.560-1.265, 0.040
0.087, 0.043-0.089, 0.189-0.453, 0.69-2.91, 3.43-14.20, 6.17-16.25, and 9.1-20.0
mg.kg-1, respectively. Furthermore, the concentrations of Pb, Cu, As, Hg, Cd, and
Cr in young tea leaves and mature tea leaves were all lower than the standard
limit values (5.0, 30, 2.0, 0.3, 1.0, and 5.0 mg.kg-1 for Pb, Cu, As, Hg, Cd, and
Cr, respectively) in China. Besides, the accumulation ability of tea leaves to Mn
was the strongest, and the average bioconcentration factor (BCF) of Mn in mature
tea leaves was 12.5. In addition, the average target hazard quotients (THQ) were
all less than one for the young tea leaves and the average aggregate risk hazard
index (HI) to adults was 0.272, indicating that there was not a potential health
risk for adults through the consumption of the infusions brewed by young tea
leaves. However, for mature tea leaves, the percentage which HI values were above
one was 38.46%, and the risk to adults via the consumption of mature tea
infusions were mainly contributed by Mn and Al.
PMID- 29342878
TI - Improved Photo-Ignition of Carbon Nanotubes/Ferrocene Using a Lipophilic
Porphyrin under White Power LED Irradiation.
AB - The aim of this work is to investigate and characterize the photo-ignition
process of dry multi-walled carbon nanotubes (MWCNTs) mixed with ferrocene
(FeCp2) powder, using an LED (light-emitting diode) as the light source, a
combination that has never been used, to the best of our knowledge. The ignition
process was improved by adding a lipophilic porphyrin (H2Pp) in powder to the
MWCNTs/FeCp2 mixtures-thus, a lower ignition threshold was obtained. The ignition
tests were carried out by employing a continuous emission and a pulsed white LED
in two test campaigns. In the first, two MWCNT typologies, high purity (HP) and
industrial grade (IG), were used without porphyrin, obtaining, for both, similar
ignition thresholds. Furthermore, comparing ignition thresholds obtained with the
LED source with those previously obtained with a Xenon (Xe) lamp, a significant
reduction was observed. In the second test campaign, ignition tests were carried
out by means of a properly driven and controlled pulsed XHP70 LED source. The
minimum ignition energy (MIE) of IG-MWCNTs/FeCp2 samples was determined by
varying the duration of the light pulse. Experimental results show that ignition
is obtained with a pulse duration of 110 ms and a MIE density of 266 mJ/cm2. The
significant reduction of the MIE value (10-40%), observed when H2Pp in powder
form was added to the MWCNTs/FeCp2 mixtures, was ascribed to the improved
photoexcitation and charge transfer properties of the lipophilic porphyrin
molecules.
PMID- 29342881
TI - Development of Self-Assembled Nanoribbon Bound Peptide-Polyaniline Composite
Scaffolds and Their Interactions with Neural Cortical Cells.
AB - Degenerative neurological disorders and traumatic brain injuries cause
significant damage to quality of life and often impact survival. As a result,
novel treatments are necessary that can allow for the regeneration of neural
tissue. In this work, a new biomimetic scaffold was designed with potential for
applications in neural tissue regeneration. To develop the scaffold, we first
prepared a new bolaamphiphile that was capable of undergoing self-assembly into
nanoribbons at pH 7. Those nanoribbons were then utilized as templates for
conjugation with specific proteins known to play a critical role in neural tissue
growth. The template (Ile-TMG-Ile) was prepared by conjugating
tetramethyleneglutaric acid with isoleucine and the ability of the bolaamphiphile
to self-assemble was probed at a pH range of 4 through 9. The nanoribbons formed
under neutral conditions were then functionalized step-wise with the basement
membrane protein laminin, the neurotropic factor artemin and Type IV collagen.
The conductive polymer polyaniline (PANI) was then incorporated through
electrostatic and pi-pi stacking interactions to the scaffold to impart
electrical properties. Distinct morphology changes were observed upon conjugation
with each layer, which was also accompanied by an increase in Young's Modulus as
well as surface roughness. The Young's Modulus of the dried PANI-bound
biocomposite scaffolds was found to be 5.5 GPa, indicating the mechanical
strength of the scaffold. Thermal phase changes studied indicated broad
endothermic peaks upon incorporation of the proteins which were diminished upon
binding with PANI. The scaffolds also exhibited in vitro biodegradable behavior
over a period of three weeks. Furthermore, we observed cell proliferation and
short neurite outgrowths in the presence of rat neural cortical cells, confirming
that the scaffolds may be applicable in neural tissue regeneration. The
electrochemical properties of the scaffolds were also studied by generating I-V
curves by conducting cyclic voltammetry. Thus, we have developed a new biomimetic
composite scaffold that may have potential applications in neural tissue
regeneration.
PMID- 29342879
TI - Ophthalmic Drug Delivery Systems for Antibiotherapy-A Review.
AB - The last fifty years, ophthalmic drug delivery research has made much progress,
challenging scientists about the advantages and limitations of this drug delivery
approach. Topical eye drops are the most commonly used formulation in ocular drug
delivery. Despite the good tolerance for patients, this topical administration is
only focus on the anterior ocular diseases and had a high precorneal loss of
drugs due to the tears production and ocular barriers. Antibiotics are popularly
used in solution or in ointment for the ophthalmic route. However, their local
bioavailability needs to be improved in order to decrease the frequency of
administrations and the side effects and to increase their therapeutic
efficiency. For this purpose, sustained release forms for ophthalmic delivery of
antibiotics were developed. This review briefly describes the ocular
administration with the ocular barriers and the currently topical forms. It
focuses on experimental results to bypass the limitations of ocular antibiotic
delivery with new ocular technology as colloidal and in situ gelling systems or
with the improvement of existing forms as implants and contact lenses.
Nanotechnology is presently a promising drug delivery way to provide protection
of antibiotics and improve pathway through ocular barriers and deliver drugs to
specific target sites.
PMID- 29342883
TI - Development of SiC Nanoparticles and Second Phases Synergistically Reinforced Mg
Based Composites Processed by Multi-Pass Forging with Varying Temperatures.
AB - In this study, SiC nanoparticles were added into matrix alloy through a
combination of semisolid stirring and ultrasonic vibration while dynamic
precipitation of second phases was obtained through multi-pass forging with
varying temperatures. During single-pass forging of the present composite, as the
deformation temperature increased, the extent of recrystallization increased, and
grains were refined due to the inhibition effect of the increasing amount of
dispersed SiC nanoparticles. A small amount of twins within the SiC nanoparticle
dense zone could be found while the precipitated phases of Mg17Al12 in long
strips and deformation bands with high density dislocations were formed in the
particle sparse zone after single-pass forging at 350 degrees C. This indicated
that the particle sparse zone was mainly deformed by dislocation slip while the
nanoparticle dense zone may have been deformed by twinning. The yield strength
and ultimate tensile strength of the composites were gradually enhanced through
increasing the single-pass forging temperature from 300 degrees C to 400
degrees C, which demonstrated that initial high forging temperature contributed
to the improvement of the mechanical properties. During multi-pass forging with
varying temperatures, the grain size of the composite was gradually decreased
while the grain size distribution tended to be uniform with reducing the
deformation temperature and extending the forging passes. In addition, the amount
of precipitated second phases was significantly increased compared with that
after multi-pass forging under a constant temperature. The improvement in the
yield strength of the developed composite was related to grain refinement
strengthening and Orowan strengthening resulting from synergistical effect of the
externally applied SiC nanoparticles and internally precipitated second phases.
PMID- 29342884
TI - Effect of the Extraction Process on the Biological Activity of Lyophilized
Apricot Extracts Recovered from Apricot Pomace.
AB - The preservation of polyphenols in fruits by lyophilization has gained great
interest in the recent decades. The present study aims to assess the impact of
the pre-treatment extraction methods heat-assisted extraction (HAE) and infrared
(IR) on lyophilized apricot pomace extracts. Then to test the conservation of
polyphenols quantities as well as their bioactivities (antiradical and
antibacterial) in lyophilized extract. An aqueous extract was obtained through
either heat-assisted extraction or infrared pre-treatments then lyophilized to
obtain a dried form. Results showed that the content of polyphenols, the
antiradical and antibacterial activities in lyophilized extracts exhibited a
slighter decrease in infrared sample compared to the heat-assisted extraction
ones. The High-performance liquid chromatography (HPLC) analysis showed that
lyophilized extracts IR and HAE preserved the same phenolic molecules (rutin,
catechin and epicatechin) detected in liquid extracts (IR and HAE) with a smaller
yield. Lyophilization can be used as a widely process in the food industry to
conserve many bioactive molecules.
PMID- 29342882
TI - Implication of Soluble Forms of Cell Adhesion Molecules in Infectious Disease and
Tumor: Insights from Transgenic Animal Models.
AB - Cell adhesion molecules (CAMs) are surface ligands, usually glycoproteins, which
mediate cell-to-cell adhesion. They play a critical role in maintaining tissue
integrity and mediating migration of cells, and some of them also act as viral
receptors. It has been known that soluble forms of the viral receptors bind to
the surface glycoproteins of the viruses and neutralize them, resulting in
inhibition of the viral entry into cells. Nectin-1 is one of important CAMs
belonging to immunoglobulin superfamily and herpesvirus entry mediator (HVEM) is
a member of the tumor necrosis factor (TNF) receptor family. Both CAMs also act
as alphaherpesvirus receptor. Transgenic mice expressing the soluble form of
nectin-1 or HVEM showed almost complete resistance against the
alphaherpesviruses. As another CAM, sialic acid-binding immunoglobulin-like
lectins (Siglecs) that recognize sialic acids are also known as an immunoglobulin
superfamily member. Siglecs play an important role in the regulation of immune
cell functions in infectious diseases, inflammation, neurodegeneration,
autoimmune diseases and cancer. Siglec-9 is one of Siglecs and capsular
polysaccharide (CPS) of group B Streptococcus (GBS) binds to Siglec-9 on
neutrophils, leading to suppress host immune response and provide a survival
advantage to the pathogen. In addition, Siglec-9 also binds to tumor-produced
mucins such as MUC1 to lead negative immunomodulation. Transgenic mice expressing
the soluble form of Siglec-9 showed significant resistance against GBS infection
and remarkable suppression of MUC1 expressing tumor proliferation. This review
describes recent developments in the understanding of the potency of soluble
forms of CAMs in the transgenic mice and discusses potential therapeutic
interventions that may alter the outcomes of certain diseases.
PMID- 29342887
TI - A Novel Synthesis Routine for Woodwardite and Its Affinity towards Light (La, Ce,
Nd) and Heavy (Gd and Y) Rare Earth Elements.
AB - A synthetic Cu-Al-SO4 layered double hydroxide (LDH), analogue to the mineral
woodwardite [Cu1-xAlx(SO4)x/2(OH)2.nH2O], with x < 0.5 and n <= 3x/2, was
synthesised by adding a solution of Cu and Al sulphates to a solution with NaOH.
The pH values were kept constant at 8.0 and 10.0 by a continuous addition of
NaOH. The material obtained had poor crystallinity, turbostratic structure, and
consisted of nanoscopic crystallites. The analyses performed in order to
characterise the obtained materials (X-ray diffraction (XRD), thermogravimetry
(TG), and Fourier Transform Infra-Red (FTIR) spectroscopy) showed that the Cu-Al
SO4 LDH is very similar to woodwardite, although it has a smaller layer spacing,
presumably due to a lesser water content than in natural samples. The synthesis
was performed by adding light rare earth elements (LREEs) (La, Ce, and Nd) and
heavy rare earth elements (HREEs) (Gd and Y) in order to test the affinity of the
Cu-Al-SO4 LDH to the incorporation of REEs. The concentration of rare earth
elements (REEs) in the solid fraction was in the range of 3.5-8 wt %. The results
showed a good affinity for HREE and Nd, especially for materials synthesised at
pH 10.0, whereas the affinities for Ce and La were much lower or non-existent.
The thermal decomposition of the REE-doped materials generates a mixture of Cu,
Al, and REE oxides, making them interesting as precursors in REE oxide synthesis.
PMID- 29342886
TI - A Xylenol Orange-Based Screening Assay for the Substrate Specificity of Flavin
Dependent para-Phenol Oxidases.
AB - Vanillyl alcohol oxidase (VAO) and eugenol oxidase (EUGO) are flavin-dependent
enzymes that catalyse the oxidation of para-substituted phenols. This makes them
potentially interesting biocatalysts for the conversion of lignin-derived
aromatic monomers to value-added compounds. To facilitate their biocatalytic
exploitation, it is important to develop methods by which variants of the enzymes
can be rapidly screened for increased activity towards substrates of interest.
Here, we present the development of a screening assay for the substrate
specificity of para-phenol oxidases based on the detection of hydrogen peroxide
using the ferric-xylenol orange complex method. The assay was used to screen the
activity of VAO and EUGO towards a set of twenty-four potential substrates. This
led to the identification of 4-cyclopentylphenol as a new substrate of VAO and
EUGO and 4-cyclohexylphenol as a new substrate of VAO. Screening of a small
library of VAO and EUGO active-site variants for alterations in their substrate
specificity led to the identification of a VAO variant (T457Q) with increased
activity towards vanillyl alcohol (4-hydroxy-3-methoxybenzyl alcohol) and a EUGO
variant (V436I) with increased activity towards chavicol (4-allylphenol) and 4
cyclopentylphenol. This assay provides a quick and efficient method to screen the
substrate specificity of para-phenol oxidases, facilitating the enzyme
engineering of known para-phenol oxidases and the evaluation of the substrate
specificity of novel para-phenol oxidases.
PMID- 29342885
TI - Alcohol-Derived Acetaldehyde Exposure in the Oral Cavity.
AB - Alcohol is classified by the International Agency for Research on Cancer (IARC)
as a human carcinogen and its consumption has been associated to an increased
risk of liver, breast, colorectum, and upper aerodigestive tract (UADT) cancers.
Its mechanisms of carcinogenicity remain unclear and various hypotheses have been
formulated depending on the target organ considered. In the case of UADT cancers,
alcohol's major metabolite acetaldehyde seems to play a crucial role.
Acetaldehyde reacts with DNA inducing modifications, which, if not repaired, can
result in mutations and lead to cancer development. Despite alcohol being mainly
metabolized in the liver, several studies performed in humans found higher levels
of acetaldehyde in saliva compared to those found in blood immediately after
alcohol consumption. These results suggest that alcohol-derived acetaldehyde
exposure may occur in the oral cavity independently from liver metabolism. This
hypothesis is supported by our recent results showing the presence of
acetaldehyde-related DNA modifications in oral cells of monkeys and humans
exposed to alcohol, overall suggesting that the alcohol metabolism in the oral
cavity is an independent cancer risk factor. This review article will focus on
illustrating the factors modulating alcohol-derived acetaldehyde exposure and
effects in the oral cavity.
PMID- 29342888
TI - Surface Properties of Nanostructured, Porous ZnO Thin Films Prepared by Direct
Current Reactive Magnetron Sputtering.
AB - In this paper, the results of detailed X-ray photoelectron spectroscopy (XPS)
studies combined with atomic force microscopy (AFM) investigation concerning the
local surface chemistry and morphology of nanostructured ZnO thin films are
presented. They have been deposited by direct current (DC) reactive magnetron
sputtering under variable absolute Ar/O2 flows (in sccm): 3:0.3; 8:0.8; 10:1;
15:1.5; 20:2, and 30:3, respectively. The XPS studies allowed us to obtain the
information on: (1) the relative concentrations of main elements related to their
surface nonstoichiometry; (2) the existence of undesired C surface
contaminations; and (3) the various forms of surface bondings. It was found that
only for the nanostructured ZnO thin films, deposited under extremely different
conditions, i.e., for Ar/O2 flow ratio equal to 3:0.3 and 30:3 (in sccm),
respectively, an evident and the most pronounced difference had been observed.
The same was for the case of AFM experiments. What is crucial, our experiments
allowed us to find the correlation mainly between the lowest level of C
contaminations and the local surface morphology of nanostructured ZnO thin films
obtained at the highest Ar/O2 ratio (30:3), for which the densely packaged
(agglomerated) nanograins were observed, yielding a smaller surface area for
undesired C adsorption. The obtained information can help in understanding the
reason of still rather poor gas sensor characteristics of ZnO based
nanostructures including the undesired ageing effect, being of a serious barrier
for their potential application in the development of novel gas sensor devices.
PMID- 29342890
TI - Polymer-Ceramic Composite Scaffolds: The Effect of Hydroxyapatite and beta-tri
Calcium Phosphate.
AB - The design of bioactive scaffolds with improved mechanical and biological
properties is an important topic of research. This paper investigates the use of
polymer-ceramic composite scaffolds for bone tissue engineering. Different
ceramic materials (hydroxyapatite (HA) and beta-tri-calcium phosphate (TCP)) were
mixed with poly-epsilon-caprolactone (PCL). Scaffolds with different material
compositions were produced using an extrusion-based additive manufacturing
system. The produced scaffolds were physically and chemically assessed,
considering mechanical, wettability, scanning electron microscopy and thermal
gravimetric tests. Cell viability, attachment and proliferation tests were
performed using human adipose derived stem cells (hADSCs). Results show that
scaffolds containing HA present better biological properties and TCP scaffolds
present improved mechanical properties. It was also possible to observe that the
addition of ceramic particles had no effect on the wettability of the scaffolds.
PMID- 29342891
TI - Influence of the Composition, Structure, and Physical and Chemical Properties of
Aluminium-Oxide-Based Sorbents on Water Adsorption Ability.
AB - Interaction between the water adsorption ability of aluminium-oxide-based
sorbents and their chemical composition, acid-base properties of the surface, and
textural characteristics has been analysed. Alumina desiccants were synthesized
with the centrifugal-thermal activation of gibbsite followed by the hydration of
the gibbsite under mild conditions. It was demonstrated that the multicyclic
adsorption regeneration of samples under realistic conditions results in
structural transformations and changes in the acidity of their surfaces and water
adsorption ability. The modification of pseudoboehmite with alkali ions increases
surface basicity and the dynamic capacity of adsorbents relating to water
vapours. Equations have been presented that describe the adsorption and
desorption processes taking place during water vapour adsorption with the
materials studied.
PMID- 29342892
TI - Next Generation Wireless Technologies for Internet of Things.
AB - In the fast-growing Internet of Things (IoT)[...].
PMID- 29342889
TI - A Case-Control Study of the Genetic Variability in Reactive Oxygen Species
Metabolizing Enzymes in Melanoma Risk.
AB - Recent studies have shown that ultraviolet (UV)-induced chemiexcitation of
melanin fragments leads to DNA damage; and chemiexcitation of melanin fragments
requires reactive oxygen species (ROS), as ROS excite an electron in the melanin
fragments. In addition, ROS also cause DNA damages on their own. We hypothesized
that ROS producing and metabolizing enzymes were major contributors in UV-driven
melanomas. In this case-control study of 349 participants, we genotyped 23
prioritized single nucleotide polymorphisms (SNPs) in nicotinamide adenine
dinucleotide phosphate (NADPH) oxidases 1 and 4 (NOX1 and NOX4, respectively),
CYBA, RAC1, superoxide dismutases (SOD1, SOD2, and SOD3) and catalase (CAT), and
analyzed their associated melanoma risk. Five SNPs, namely rs1049255 (CYBA),
rs4673 (CYBA), rs10951982 (RAC1), rs8031 (SOD2), and rs2536512 (SOD3), exhibited
significant genotypic frequency differences between melanoma cases and healthy
controls. In simple logistic regression, RAC1 rs10951982 (odds ratio (OR) 8.98,
95% confidence interval (CI): 5.08 to 16.44; p < 0.001) reached universal
significance (p = 0.002) and the minor alleles were associated with increased
risk of melanoma. In contrast, minor alleles in SOD2 rs8031 (OR 0.16, 95% CI:
0.06 to 0.39; p < 0.001) and SOD3 rs2536512 (OR 0.08, 95% CI: 0.01 to 0.31; p =
0.001) were associated with reduced risk of melanoma. In multivariate logistic
regression, RAC1 rs10951982 (OR 6.15, 95% CI: 2.98 to 13.41; p < 0.001) remained
significantly associated with increased risk of melanoma. Our results highlighted
the importance of RAC1, SOD2, and SOD3 variants in the risk of melanoma.
PMID- 29342893
TI - QTL Mapping for Fiber Quality and Yield Traits Based on Introgression Lines
Derived from Gossypium hirsutum * G. tomentosum.
AB - The tetraploid species Gossypium hirsutum is cultivated widely throughout the
world with high yield and moderate fiber quality, but its genetic basis is
narrow. A set of 107 introgression lines (ILs) was developed with an
interspecific cross using G. hirsutumacc. 4105 as the recurrent parent and G.
tomentosum as the donor parent. A specific locus amplified fragment sequencing
(SLAF-seq) strategy was used to obtain high-throughput single nucleotide
polymorphism (SNP) markers. In total, 3157 high-quality SNP markers were obtained
and further used for identification of quantitative trait loci (QTLs) for fiber
quality and yield traits evaluated in multiple environments. In total, 74 QTLs
were detected that were associated with five fiber quality traits (30 QTLs) and
eight yield traits (44 QTLs), with 2.02-30.15% of the phenotypic variance
explained (PVE), and 69 markers were found to be associated with these thirteen
traits. Eleven chromosomes in the A sub-genome (At) harbored 47 QTLs, and nine
chromosomes in the D sub-genome (Dt) harbored 27 QTLs. More than half (44 QTLs =
59.45%) showed positive additive effects for fiber and yield traits. Five QTL
clusters were identified, with three in the At, comprised of thirteen QTLs, and
two in the Dt comprised of seven QTLs. The ILs developed in this study and the
identified QTLs will facilitate further molecular breeding for improvement of
Upland cotton in terms of higher yield with enhanced fiber quality.
PMID- 29342894
TI - Crystallization of TiO2 Nanotubes by In Situ Heating TEM.
AB - The thermally-induced crystallization of anodically grown TiO2 amorphous
nanotubes has been studied so far under ambient pressure conditions by techniques
such as differential scanning calorimetry and in situ X-ray diffraction, then
looking at the overall response of several thousands of nanotubes in a carpet
arrangement. Here we report a study of this phenomenon based on an in situ
transmission electron microscopy approach that uses a twofold strategy. First, a
group of some tens of TiO2 amorphous nanotubes was heated looking at their
electron diffraction pattern change versus temperature, in order to determine
both the initial temperature of crystallization and the corresponding crystalline
phases. Second, the experiment was repeated on groups of few nanotubes, imaging
their structural evolution in the direct space by spherical aberration-corrected
high resolution transmission electron microscopy. These studies showed that,
differently from what happens under ambient pressure conditions, under the
microscope's high vacuum (p < 10-5 Pa) the crystallization of TiO2 amorphous
nanotubes starts from local small seeds of rutile and brookite, which then grow
up with the increasing temperature. Besides, the crystallization started at
different temperatures, namely 450 and 380 degrees C, when the in situ heating
was performed irradiating the sample with electron beam energy of 120 or 300 keV,
respectively. This difference is due to atomic knock-on effects induced by the
electron beam with diverse energy.
PMID- 29342895
TI - Optimization of Extraction Conditions and Characterization of Pepsin-Solubilised
Collagen from Skin of Giant Croaker (Nibea japonica).
AB - In the present study, response surface methodology was performed to investigate
the effects of extraction parameters on pepsin-solubilised collagen (PSC) from
the skin of the giant croaker Nibea japonica. The optimum extraction conditions
of PSC were as follows: concentration of pepsin was 1389 U/g, solid-liquid ratio
was 1:57 and hydrolysis time was 8.67 h. Under these conditions, the extraction
yield of PSC was up to 84.85%, which is well agreement with the predict value of
85.03%. The PSC from Nibea japonica skin was then characterized as type I
collagen by using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS
PAGE). The fourier transforms infrared spetroscopy (FTIR) analysis revealed that
PSC maintains its triple-helical structure by the hydrogen bond. All PSCs were
soluble in the pH range of 1.0-4.0 and decreases in solubility were observed at
neutral or alkaline conditions. All PSCs had a decrease in solubility in the
presence of sodium chloride, especially with a concentration above 2%. So, the
Nibea japonica skin could serve as another potential source of collagen.
PMID- 29342896
TI - How Does Counselling in a Stationary Health Care Setting Affect the Attendance in
a Standardised Sports Club Programme? Process Evaluation of a Quasi-Experimental
Study.
AB - Actions in partnership across sectors is one principle for the promotion of
health behaviours. The objective of this study was to describe the participation
in a sports club-based exercise programme-named JACKPOT-following an intervention
in a health care setting. Focus was given to the recruitment into JACKPOT, the
attendance level, and whether the different programme elements were implemented
as intented. The practicability of the project was also retrospectively rated.
Participants were 238 inactive people (50% women) between 30 and 65 years of age
who attended a health resort. Of these, 77% were assigned to the intervention
group (IG). The recruitment into the 12 JACKPOT sessions and the attendance
levels were recorded via attendance lists. The implementation of the intervention
standards was assessed with structured interviews and participatory observation.
The Pragmatic Explanatory Continuum Indicator Summary (PRECIS)-2 tool served to
rate the practicability of the project. Almost 50% of the IG subjects attended
JACKPOT sessions at least once and 54% of the attenders visited >=75% of the 12
sessions. Some of the programme elements were not delivered fully. The process
evaluation results showed that the project worked in a real-world setting, and
also uncovered potential reasons such as incomplete information delivery for the
moderate recruitment and attendance level.
PMID- 29342897
TI - Replication Strategy for Spatiotemporal Data Based on Distributed Caching System.
AB - The replica strategy in distributed cache can effectively reduce user access
delay and improve system performance. However, developing a replica strategy
suitable for varied application scenarios is still quite challenging, owing to
differences in user access behavior and preferences. In this paper, a replication
strategy for spatiotemporal data (RSSD) based on a distributed caching system is
proposed. By taking advantage of the spatiotemporal locality and correlation of
user access, RSSD mines high popularity and associated files from historical user
access information, and then generates replicas and selects appropriate cache
node for placement. Experimental results show that the RSSD algorithm is simple
and efficient, and succeeds in significantly reducing user access delay.
PMID- 29342899
TI - Smartphone Spectrometers.
AB - Smartphones are playing an increasing role in the sciences, owing to the
ubiquitous proliferation of these devices, their relatively low cost, increasing
processing power and their suitability for integrated data acquisition and
processing in a 'lab in a phone' capacity. There is furthermore the potential to
deploy these units as nodes within Internet of Things architectures, enabling
massive networked data capture. Hitherto, considerable attention has been focused
on imaging applications of these devices. However, within just the last few
years, another possibility has emerged: to use smartphones as a means of
capturing spectra, mostly by coupling various classes of fore-optics to these
units with data capture achieved using the smartphone camera. These highly novel
approaches have the potential to become widely adopted across a broad range of
scientific e.g., biomedical, chemical and agricultural application areas. In this
review, we detail the exciting recent development of smartphone spectrometer
hardware, in addition to covering applications to which these units have been
deployed, hitherto. The paper also points forward to the potentially highly
influential impacts that such units could have on the sciences in the coming
decades.
PMID- 29342898
TI - Associations between Zinc Deficiency and Metabolic Abnormalities in Patients with
Chronic Liver Disease.
AB - Zinc (Zn) is an essential trace element which has favorable antioxidant, anti
inflammatory, and apoptotic effects. The liver mainly plays a crucial role in
maintaining systemic Zn homeostasis. Therefore, the occurrence of chronic liver
diseases, such as chronic hepatitis, liver cirrhosis, or fatty liver, results in
the impairment of Zn metabolism, and subsequently Zn deficiency. Zn deficiency
causes plenty of metabolic abnormalities, including insulin resistance, hepatic
steatosis and hepatic encephalopathy. Inversely, metabolic abnormalities like
hypoalbuminemia in patients with liver cirrhosis often result in Zn deficiency.
Recent studies have revealed the putative mechanisms by which Zn deficiency
evokes a variety of metabolic abnormalities in chronic liver disease. Zn
supplementation has shown beneficial effects on such metabolic abnormalities in
experimental models and actual patients with chronic liver disease. This review
summarizes the pathogenesis of metabolic abnormalities deriving from Zn
deficiency and the favorable effects of Zn administration in patients with
chronic liver disease. In addition, we also highlight the interactions between Zn
and other trace elements, vitamins, amino acids, or hormones in such patients.
PMID- 29342900
TI - Increasing the Intensity over Time of an Electric-Assist Bike Based on the User
and Route: The Bike Becomes the Gym.
AB - Nowadays, many citizens have busy days that make finding time for physical
activity difficult. Thus, it is important to provide citizens with tools that
allow them to introduce physical activity into their lives as part of the day's
routine. This article proposes an app for an electric pedal-assist-system (PAS)
bicycle that increases the pedaling intensity so the bicyclist can achieve higher
and higher levels of physical activity. The app includes personalized assist
levels that have been adapted to the user's strength/ability and a profile of the
route, segmented according to its slopes. Additionally, a social component
motivates interaction and competition between users based on a scoring system
that shows the level of their performances. To test the training module, a case
study in three different European countries lasted four months and included nine
people who traveled 551 routes. The electric PAS bicycle with the app that
increases intensity of physical activity shows promise for increasing levels of
physical activity as a regular part of the day.
PMID- 29342901
TI - Omega-3 Polyunsaturated Fatty Acids Time-Dependently Reduce Cell Viability and
Oncogenic MicroRNA-21 Expression in Estrogen Receptor-Positive Breast Cancer
Cells (MCF-7).
AB - The omega-3 polyunsaturated fatty acid (n-3 PUFA), alpha-linolenic acid (ALA),
and its metabolites, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA),
independently reduce the growth of breast cancer cells in vitro, but the
mechanisms, which may involve microRNA (miRNA), are still unclear. The expression
of the oncomiR, miR-21, is reduced by DHA treatment, but the effects of ALA on
miR-21, alone or combined with EPA and DHA under physiologically relevant
concentrations, have not been investigated. The effects of ALA alone and +/-EPA
and DHA at the blood molar ratios seen in either humans (1.0:1.0:2.5,
ALA:EPA:DHA) or mice (1.0:0.4:3.1, ALA:EPA:DHA) post flaxseed oil consumption
(containing ALA) were assessed in vitro in MCF-7 breast cancer cells. Cell
viability and the expression of miR-21 and its molecular target, phosphatase and
tension homolog (PTEN, gene and protein), at different time points, were
examined. At 1, 3, 48 and 96 h ALA alone and 24 h animal ratio treatments
significantly reduced MCF-7 cell viability, while 1 and 3 h ALA alone and human
and animal ratio treatments all significantly reduced miR-21 expression, and 24 h
animal ratio treatment reduced miR-21 expression; these effects were not
associated with changes in PTEN gene or protein expressions. We showed for the
first time that ALA alone or combined with EPA and DHA at levels seen in human
and animal blood post-ALA consumption can significantly reduce cell viability and
modulate miR-21 expression in a time- and concentration-dependent manner, with
the animal ratio containing higher DHA having a greater effect. The time
dependency of miR-21 effects suggests the significance of considering time as a
variable in miRNA studies, particularly of miR-21.
PMID- 29342902
TI - Design and Testing of a Flexible Inclinometer Probe for Model Tests of Landslide
Deep Displacement Measurement.
AB - The physical model test of landslides is important for studying landslide
structural damage, and parameter measurement is key in this process. To meet the
measurement requirements for deep displacement in landslide physical models, an
automatic flexible inclinometer probe with good coupling and large deformation
capacity was designed. The flexible inclinometer probe consists of several
gravity acceleration sensing units that are protected and positioned by silicon
encapsulation, all the units are connected to a 485-comunication bus. By sensing
the two-axis tilt angle, the direction and magnitude of the displacement for a
measurement unit can be calculated, then the overall displacement is accumulated
according to all units, integrated from bottom to top in turn. In the conversion
from angle to displacement, two spline interpolation methods are introduced to
correct and resample the data; one is to interpolate the displacement after
conversion, and the other is to interpolate the angle before conversion; compared
with the result read from checkered paper, the latter is proved to have a better
effect, with an additional condition that the displacement curve move up half the
length of the unit. The flexible inclinometer is verified with respect to its
principle and arrangement by a laboratory physical model test, and the test
results are highly consistent with the actual deformation of the landslide model.
PMID- 29342904
TI - Improved Coarray Interpolation Algorithms with Additional Orthogonal Constraint
for Cyclostationary Signals.
AB - Many modulated signals exhibit a cyclostationarity property, which can be
exploited in direction-of-arrival (DOA) estimation to effectively eliminate
interference and noise. In this paper, our aim is to integrate the
cyclostationarity with the spatial domain and enable the algorithm to estimate
more sources than sensors. However, DOA estimation with a sparse array is
performed in the coarray domain and the holes within the coarray limit the usage
of the complete coarray information. In order to use the complete coarray
information to increase the degrees-of-freedom (DOFs), sparsity-aware-based
methods and the difference coarray interpolation methods have been proposed. In
this paper, the coarray interpolation technique is further explored with
cyclostationary signals. Besides the difference coarray model and its
corresponding Toeplitz completion formulation, we build up a sum coarray model
and formulate a Hankel completion problem. In order to further improve the
performance of the structured matrix completion, we define the spatial spectrum
sampling operations and the derivative (conjugate) correlation subspaces, which
can be exploited to construct orthogonal constraints for the autocorrelation
vectors in the coarray interpolation problem. Prior knowledge of the source
interval can also be incorporated into the problem. Simulation results
demonstrate that the additional constraints contribute to a remarkable
performance improvement.
PMID- 29342903
TI - Application of Nanoparticle Technologies in the Combat against Anti-Microbial
Resistance.
AB - Anti-microbial resistance is a growing problem that has impacted the world and
brought about the beginning of the end for the old generation of antibiotics.
Increasingly, more antibiotics are being prescribed unnecessarily and this
reckless practice has resulted in increased resistance towards these drugs,
rendering them useless against infection. Nanotechnology presents a potential
answer to anti-microbial resistance, which could stimulate innovation and create
a new generation of antibiotic treatments for future medicines. Preserving
existing antibiotic activity through novel formulation into or onto
nanotechnologies can increase clinical longevity of action against infection.
Additionally, the unique physiochemical properties of nanoparticles can provide
new anti-bacterial modes of action which can also be explored. Simply
concentrating on antibiotic prescribing habits will not resolve the issue but
rather mitigate it. Thus, new scientific approaches through the development of
novel antibiotics and formulations is required in order to employ a new
generation of therapies to combat anti-microbial resistance.
PMID- 29342905
TI - Closed-Form Algorithm for 3-D Near-Field OFDM Signal Localization under Uniform
Circular Array.
AB - Due to its widespread application in communications, radar, etc., the orthogonal
frequency division multiplexing (OFDM) signal has become increasingly urgent in
the field of localization. Under uniform circular array (UCA) and near-field
conditions, this paper presents a closed-form algorithm based on phase difference
for estimating the three-dimensional (3-D) location (azimuth angle, elevation
angle, and range) of the OFDM signal. In the algorithm, considering that it is
difficult to distinguish the frequency of the OFDM signal's subcarriers and the
phase-based method is always affected by errors of the frequency estimation, this
paper employs sparse representation (SR) to obtain the super-resolution
frequencies and the corresponding phases of subcarriers. Further, as the phase
differences of the adjacent sensors including azimuth angle, elevation angle and
range parameters can be expressed as indefinite equations, the near-field OFDM
signal's 3-D location is obtained by employing the least square method, where the
phase differences are based on the average of the estimated subcarriers. Finally,
the performance of the proposed algorithm is demonstrated by several simulations.
PMID- 29342906
TI - Modelling and Characterization of Effective Thermal Conductivity of Single Hollow
Glass Microsphere and Its Powder.
AB - Tiny hollow glass microsphere (HGM) can be applied for designing new light
weighted and thermal-insulated composites as high strength core, owing to its
hollow structure. However, little work has been found for studying its own
overall thermal conductivity independent of any matrix, which generally cannot be
measured or evaluated directly. In this study, the overall thermal conductivity
of HGM is investigated experimentally and numerically. The experimental
investigation of thermal conductivity of HGM powder is performed by the transient
plane source (TPS) technique to provide a reference to numerical results, which
are obtained by a developed three-dimensional two-step hierarchical computational
method. In the present method, three heterogeneous HGM stacking elements
representing different distributions of HGMs in the powder are assumed. Each
stacking element and its equivalent homogeneous solid counterpart are,
respectively, embedded into a fictitious matrix material as fillers to form two
equivalent composite systems at different levels, and then the overall thermal
conductivity of each stacking element can be numerically determined through the
equivalence of the two systems. The comparison of experimental and computational
results indicates the present computational modeling can be used for effectively
predicting the overall thermal conductivity of single HGM and its powder in a
flexible way. Besides, it is necessary to note that the influence of thermal
interfacial resistance cannot be removed from the experimental results in the TPS
measurement.
PMID- 29342907
TI - An Uncommon Case of Pediatric Esthesioneuroblastoma Presenting as SIADH: 18F-FDG
PET/CT in Staging and Post-Therapeutic Assessment.
AB - Esthesioneuroblastoma (ENB) is an uncommon neuroendocrine tumor originating from
the olfactory neuroepithelium and accounts for 3-6% of all intranasal tumors [1].
ENBs can be locally aggressive and cause invasion and destruction of surrounding
structures. Histological grading and clinical stage at presentation are highly
predictive of survival and especially presence of lymph node and distant
metastases are determining prognostic factors [2,3,4,5]. Thus, reliable imaging
is essential in these patients. Conventional imaging modalities for staging ENB
are magnetic resonance imaging (MRI) and computed tomography (CT). However,
fluorine-18 fluoro-2-deoxy-d-glucose positron emission tomography/CT (18F-FDG
PET/CT) has been reported as a valuable adjunct and was found to upstage 36% of
ENB patients compared to conventional imaging [6]. We present a case
demonstrating the diagnostic work-up and follow-up with 18F-FDG PET/CT in a young
patient with ENB with a highly atypical clinical presentation.
PMID- 29342908
TI - Rapid 3D Reconstruction for Image Sequence Acquired from UAV Camera.
AB - In order to reconstruct three-dimensional (3D) structures from an image sequence
captured by unmanned aerial vehicles' camera (UAVs) and improve the processing
speed, we propose a rapid 3D reconstruction method that is based on an image
queue, considering the continuity and relevance of UAV camera images. The
proposed approach first compresses the feature points of each image into three
principal component points by using the principal component analysis method. In
order to select the key images suitable for 3D reconstruction, the principal
component points are used to estimate the interrelationships between images.
Second, these key images are inserted into a fixed-length image queue. The
positions and orientations of the images are calculated, and the 3D coordinates
of the feature points are estimated using weighted bundle adjustment. With this
structural information, the depth maps of these images can be calculated. Next,
we update the image queue by deleting some of the old images and inserting some
new images into the queue, and a structural calculation of all the images can be
performed by repeating the previous steps. Finally, a dense 3D point cloud can be
obtained using the depth-map fusion method. The experimental results indicate
that when the texture of the images is complex and the number of images exceeds
100, the proposed method can improve the calculation speed by more than a factor
of four with almost no loss of precision. Furthermore, as the number of images
increases, the improvement in the calculation speed will become more noticeable.
PMID- 29342909
TI - Spirostane-Type Saponins Obtained from Yucca schidigera.
AB - It is well known that spirostane-type saponins show various bioactivities. In our
on-going program of screening these kinds of constituents from natural products,
Yucca schidigera was found to be rich in them, and nine new spirostanol saponins,
Yucca spirostanosides A1 (1), A2 (2), B1 (3), B2 (4), B3 (5), C1 (6), C2 (7), C3
(8), and D1 (9), together with five known ones (10-14) were isolated from the
plant. Their structures were elucidated by extensive spectroscopic methods,
including 1D and 2D NMR and MS spectra, and comparing with published data.
PMID- 29342910
TI - Academic Stress and Self-Regulation among University Students in Malaysia:
Mediator Role of Mindfulness.
AB - Academic stress is the most common emotional or mental state that students
experience during their studies. Stress is a result of a wide range of issues,
including test and exam burden, a demanding course, a different educational
system, and thinking about future plans upon graduation. A sizeable body of
literature in stress management research has found that self-regulation and being
mindful will help students to cope up with the stress and dodge long-term
negative consequences, such as substance abuse. The present study aims to
investigate the influence of academic stress, self-regulation, and mindfulness
among undergraduate students in Klang Valley, Malaysia, and to identify
mindfulness as the mediator between academic stress and self-regulation. For this
study, a total of 384 undergraduate students in Klang Valley, Malaysia were
recruited. Using Correlational analysis, results revealed that there was a
significant relationship between academic stress, self-regulation, and
mindfulness. However, using SPSS mediational analysis, mindfulness did not prove
the mediator role in the study.
PMID- 29342915
TI - Correction: An Extended Damage Plasticity Model for Shotcrete: Formulation and
Comparison with Other Shotcrete Models.
AB - The authors would like to correct following typing errors: For (3) and (4), the
correct expressions are given as[...].
PMID- 29342911
TI - Effects of Acanthopanax senticosus on Brain Injury Induced by Simulated Spatial
Radiation in Mouse Model Based on Pharmacokinetics and Comparative Proteomics.
AB - The active compounds in Acanthopanax senticosus (AS) have different
pharmacokinetic characteristics in mouse models. Cmax and AUC of Acanthopanax
senticosus polysaccharides (ASPS) were significantly reduced in radiation-injured
mice, suggesting that the blood flow of mouse was blocked or slowed, due to the
pathological state of ischemia and hypoxia, which are caused by radiation. In
contrast, the ability of various metabolizing enzymes to inactivate, capacity of
biofilm transport decrease, and lessening of renal blood flow accounts for
radiation, resulting in the accumulation of syringin and eleutheroside E in the
irradiated mouse. Therefore, there were higher pharmacokinetic parameters-AUC,
MRT, and t1/2 of the two compounds in radiation-injured mouse, when compared with
normal mouse. In order to investigate the intrinsic mechanism of AS on radiation
injury, AS extract's protective effects on brain, the main part of mouse that
suffered from radiation, were explored. The function of AS extract in repressing
expression changes of radiation response proteins in prefrontal cortex (PFC) of
mouse brain included tubulin protein family (alpha-, beta-tubulin subunits),
dihydropyrimidinase-related protein 2 (CRMP2), gamma-actin, 14-3-3 protein family
(14-3-3zeta, epsilon), heat shock protein 90beta (HSP90beta), and enolase 2. The
results demonstrated the AS extract had positive effects on nerve cells'
structure, adhesion, locomotion, fission, and phagocytosis, through regulating
various action pathways, such as Hippo, phagosome, PI3K/Akt (phosphatidylinositol
3 kinase/protein kinase B), Neurotrophin, Rap1 (Ras-related protein RAP-1A), gap
junction glycolysis/gluconeogenesis, and HIF-1 (Hypoxia-inducible factor 1)
signaling pathways to maintain normal mouse neurological activity. All of the
results indicated that AS may be a promising alternative medicine for the
treatment of radiation injury in mouse brain. It would be tested that whether the
bioactive ingredients of AS could be effective through the blood-brain barrier in
the future.
PMID- 29342916
TI - Coffee Intake and Liver Steatosis: A Population Study in a Mediterranean Area.
AB - Coffee drinking seems to have several beneficial effects on health outcomes.
However, the effect on hepatic steatosis, depending on a high alcohol consumption
(AFLD, alcoholic fatty liver disease) or on metabolic factors (non-alcoholic
fatty liver disease, NAFLD), is still equivocal. Thus, we aimed to explore the
potential association between coffee consumption and the presence and severity of
hepatic steatosis in people with NAFLD or AFLD. In this cross-sectional study,
coffee drinking was recorded using a semi-quantitative food frequency
questionnaire, and categorized as yes vs. no and as 0, 1, 2, >=3. The degree of
fatty liver was assessed through a standardized ultrasound examination (score 0
to 6, with higher values reflecting higher severity). Liver steatosis was
classified as NAFLD or AFLD on daily alcohol intake >30 g/day for men and >20
g/day for women. This study included 2819 middle-aged participants; the great
majority were coffee drinkers (86.1%). After adjusting for 12 potential
confounders, drinking coffee was not associated with decreased odds for NAFLD (n
= 916) (odds ratio, OR = 0.93; 95% confidence intervals, CI: 0.72-1.20) or AFLD
(n = 276) (OR = 1.20; 95% CI: 0.66-2.0). The consumption of coffee (categorized
as yes vs. no), or an increased consumption of coffee were not associated with
the presence of mild, moderate or severe liver steatosis in either NAFLD or AFLD.
In conclusion, coffee intake was not associated with any lower odds of hepatic
steatosis in either non-alcoholic or alcoholic forms in this large cohort of
South Italian individuals.
PMID- 29342917
TI - Nitrogen-Doped Carbon for Red Phosphorous Based Anode Materials for Lithium Ion
Batteries.
AB - Serving as conductive matrix and stress buffer, the carbon matrix plays a pivotal
role in enabling red phosphorus to be a promising anode material for high
capacity lithium ion batteries and sodium ion batteries. In this paper, nitrogen
doping is proved to effective enhance the interface interaction between carbon
and red phosphorus. In detail, the adsorption energy between phosphorus atoms and
oxygen-containing functional groups on the carbon is significantly reduced by
nitrogen doping, as verified by X-ray photoelectron spectroscopy. The adsorption
mechanisms are further revealed on the basis of DFT (the first density functional
theory) calculations. The RPNC (red phosphorus/nitrogen-doped carbon composite)
material shows higher cycling stability and higher capacity than that of RPC (red
phosphorus/carbon composite) anode. After 100 cycles, the RPNC still keeps
discharge capacity of 1453 mAh g-1 at the current density of 300 mA g-1 (the
discharge capacity of RPC after 100 cycles is 1348 mAh g-1). Even at 1200 mA g-1,
the RPNC composite still delivers a capacity of 1178 mAh g-1. This work provides
insight information about the interface interactions between composite materials,
as well as new technology develops high performance phosphorus based anode
materials.
PMID- 29342919
TI - Treatment of Sciatica Following Uterine Cancer with Acupuncture: A Case Report.
AB - For women, gynaecological or obstetrical disorders are second to disc prolapse as
the most common cause of sciatica. As not many effective conventional treatments
can be found for sciatica following uterine cancer, patients may seek assistance
from complementary and alternative medicine. Here, we present a case of a woman
with severe and chronic sciatica secondary to uterine cancer who experienced
temporary relief from acupuncture.
PMID- 29342920
TI - Asbestos Consumption in Mongolia: 1996-2014.
AB - Asbestos is still used in Mongolia in the energy and construction sectors, among
others. However, limited data is available on asbestos consumption and asbestos
related disease in Mongolia. The purpose of this paper is to present the
available information on the importation of asbestos into Mongolia. We used data
on annual asbestos imports between 1996 and 2014 from Mongolian Customs
Statistics and the National Council on Toxic and Hazardous Substances Affairs.
The uses of this material are also presented with respect to chrysotile alone.
Most asbestos is used for construction. Mongolia started using asbestos in the
energy and construction industries as thermal insulation in 1961. Asbestos is
still allowed for use in Mongolia under the Law on Toxic and Hazards Substances.
There are no asbestos mines in Mongolia, and the manufacture of asbestos
containing materials does not take place there. Thus, asbestos is mainly imported
from China and Russia. Mongolia used 44,422 metric tons of asbestos-containing
materials between 1996 and 2014. In Mongolia, with the current use of asbestos,
there will be a continuing risk of developing asbestos-related diseases from past
use, and proper oversight of asbestos-involving activities and the safe removal
and disposal of asbestos must be considered.
PMID- 29342918
TI - Abnormal Sphingolipid World in Inflammation Specific for Lysosomal Storage
Diseases and Skin Disorders.
AB - Research in recent years has shown that sphingolipids are essential signalling
molecules for the proper biological and structural functioning of cells. Long
term studies on the metabolism of sphingolipids have provided evidence for their
role in the pathogenesis of a number of diseases. As many inflammatory diseases,
such as lysosomal storage disorders and some dermatologic diseases, including
psoriasis, atopic dermatitis and ichthyoses, are associated with the altered
composition and metabolism of sphingolipids, more studies precisely determining
the responsibilities of these compounds for disease states are required to
develop novel pharmacological treatment opportunities. It is worth emphasizing
that knowledge from the study of inflammatory metabolic diseases and especially
the possibility of their treatment may lead to insight into related metabolic
pathways, including those involved in the formation of the epidermal barrier and
providing new approaches towards workable therapies.
PMID- 29342921
TI - RNA-Targeted Therapies and Amyotrophic Lateral Sclerosis.
AB - Amyotrophic lateral sclerosis (ALS) is a fatal motor disease in adults. Its
pathophysiology remains mysterious, but tremendous advances have been made with
the discovery of the most frequent mutations of its more common familial form
linked to the C9ORF72 gene. Although most cases are still considered sporadic,
these genetic mutations have revealed the role of RNA production, processing and
transport in ALS, and may be important players in all ALS forms. There are no
disease-modifying treatments for adult human neurodegenerative diseases,
including ALS. As in spinal muscular atrophy, RNA-targeted therapies have been
proposed as potential strategies for treating this neurodegenerative disorder.
Successes achieved in various animal models of ALS have proven that RNA therapies
are both safe and effective. With careful consideration of the applicability of
such therapies in humans, it is possible to anticipate ongoing in vivo research
and clinical trial development of RNA therapies for treating ALS.
PMID- 29342923
TI - Electrical Design and Evaluation of Asynchronous Serial Bus Communication Network
of 48 Sensor Platform LSIs with Single-Ended I/O for Integrated MEMS-LSI Sensors.
AB - For installing many sensors in a limited space with a limited computing resource,
the digitization of the sensor output at the site of sensation has advantages
such as a small amount of wiring, low signal interference and high scalability.
For this purpose, we have developed a dedicated Complementary Metal-Oxide
Semiconductor (CMOS) Large-Scale Integration (LSI) (referred to as "sensor
platform LSI") for bus-networked Micro-Electro-Mechanical-Systems (MEMS)-LSI
integrated sensors. In this LSI, collision avoidance, adaptation and event-driven
functions are simply implemented to relieve data collision and congestion in
asynchronous serial bus communication. In this study, we developed a network
system with 48 sensor platform LSIs based on Printed Circuit Board (PCB) in a
backbone bus topology with the bus length being 2.4 m. We evaluated the serial
communication performance when 48 LSIs operated simultaneously with the
adaptation function. The number of data packets received from each LSI was almost
identical, and the average sampling frequency of 384 capacitance channels (eight
for each LSI) was 73.66 Hz.
PMID- 29342922
TI - Can EGCG Alleviate Symptoms of Down Syndrome by Altering Proteolytic Activity?
AB - Down syndrome (DS), also known as "trisomy 21", is a genetic disorder caused by
the presence of all or part of a third copy of chromosome 21. Silencing these
extra genes is beyond existing technology and seems to be impractical. A number
of pharmacologic options have been proposed to change the quality of life and
lifespan of individuals with DS. It was reported that treatment with
epigallocatechin gallate (EGCG) improves cognitive performance in animal models
and in humans, suggesting that EGCG may alleviate symptoms of DS. Traditionally,
EGCG has been associated with the ability to reduce dual specificity tyrosine
phosphorylation regulated kinase 1A activity, which is overexpressed in trisomy
21. Based on the data available in the literature, we propose an additional way
in which EGCG might affect trisomy 21-namely by modifying the proteolytic
activity of the enzymes involved. It is known that, in Down syndrome, the nerve
growth factor (NGF) metabolic pathway is altered: first by downregulating tissue
plasminogen activator (tPA) that activates plasminogen to plasmin, an enzyme
converting proNGF to mature NGF; secondly, overexpression of metalloproteinase 9
(MMP-9) further degrades NGF, lowering the amount of mature NGF. EGCG inhibits
MMP-9, thus protecting NGF. Urokinase (uPA) and tPA are activators of
plasminogen, and uPA is inhibited by EGCG, but regardless of their structural
similarity tPA is not inhibited. In this review, we describe mechanisms of
proteolytic enzymes (MMP-9 and plasminogen activation system), their role in Down
syndrome, their inhibition by EGCG, possible degradation of this polyphenol and
the ability of EGCG and its degradation products to cross the blood-brain
barrier. We conclude that known data accumulated so far provide promising
evidence of MMP-9 inhibition by EGCG in the brain, which could slow down the
abnormal degradation of NGF.
PMID- 29342924
TI - Estrogen and Thyroid Hormone Receptor Activation by Medicinal Plants from Bahia,
Brazil.
AB - Background: A number of medicinal plants are traditionally used for metabolic
disorders in Bahia state, Brazil. The aim of this study was to evaluate the
estrogen receptor (ER) and thyroid receptor (TR) activation of crude extracts
prepared from 20 plants. Methods: Species were extracted and assayed for receptor
activation through both ER and TR gene-reporter assays, using 17beta-estradiol
and triiodothyronine (T3), respectively, as the positive controls. Results:
Cajanus cajan (Fabaceae), Abarema cochliacarpus (Fabaceae), and Borreria
verticillata (Rubiaceae) were able to activate ER as much as the positive control
(17beta-estradiol). These three plant species were also assayed for TR
activation. At the concentration of 50 ug/mL, C. cajans exerted the highest
positive modulation on TR, causing an activation of 59.9%, while B. verticillata
and A. cochliacarpus caused 30.8% and 23.3%, respectively. Conclusions: Our
results contribute towards the validation of the traditional use of C. cajans, B.
verticillata, and A. cochliacarpus in the treatment of metabolic disorders
related to ER and TR functions. The gene-reporter assay was proven effective in
screening crude plant extracts for ER/TR activation, endorsing this methodology
as an important tool for future bioprospection studies focused on identifying
novel starting molecules for the development of estrogen and thyroid agonists.
PMID- 29342925
TI - Synergistic Effect of Metal Oxide Nanoparticles on Cell Viability and Activation
of MAP Kinases and NFkappaB.
AB - In recent years, there has been an increase in the production of several types of
nanoparticles (Nps) for different purposes. Several studies have been performed
to analyse the toxicity induced by some of these individual Nps, but data are
scarce on the potential hazards or beneficial effects induced by a range of
nanomaterials in the same environment. The purpose of the study described here
was to evaluate the toxicological effects induced by in vitro exposure of human
cells to ZnO Nps in combination with different concentrations of other metal
oxide Nps (Al2O3, CeO2, TiO2 and Y2O3). The results indicate that the presence of
these Nps has synergistic or antagonistic effects on the cell death induced by
ZnO Nps, with a quite marked beneficial effect observed when high concentrations
of Nps were tested. Moreover, analysis by Western blot of the main components of
the intracellular activation routes (MAPKs and NFkappaB) again showed that the
presence of other Nps can affect cell activation. In conclusion, the presence of
several Nps in the same environment modifies the functional activity of one
individual Np. Further studies are required in order to elucidate the effects
induced by combinations of nanomaterials.
PMID- 29342926
TI - Envelope Correction of Micro-Motion Targets in the Terahertz ISAR Imaging.
AB - Motion compensation is a crucial step to inverse synthetic aperture radar
imaging, and envelope correction is the foundation of motion compensation.
Research on envelope correction based on the small-angle imaging model has
matured after years of development. However, the small-angle imaging model is not
applicable to parameter estimation and imaging of micro-motion targets. According
to the characteristics of the micro-motion targets and the superiorities of
terahertz imaging radar, an envelope correction method for micro-motion targets
in the terahertz region was proposed in this paper, including the jump error
correction based on periodic correction and drift error compensation based on
nonlinear fitting. Then a 330 GHz imaging radar and two experiments on corner
reflectors and a warhead model were introduced. The validity of the method was
verified by the experimental results, and the performance of the method was
proved by the inverse Radon transform of the range profile sequences.
PMID- 29342927
TI - The Application of Adaptive Behaviour Models: A Systematic Review.
AB - Adaptive behaviour has been viewed broadly as an individual's ability to meet the
standards of social responsibilities and independence; however, this definition
has been a source of debate amongst researchers and clinicians. Based on the rich
history and the importance of the construct of adaptive behaviour, the current
study aimed to provide a comprehensive overview of the application of adaptive
behaviour models to assessment tools, through a systematic review. A plethora of
assessment measures for adaptive behaviour have been developed in order to
adequately assess the construct; however, it appears that the only definition on
which authors seem to agree is that adaptive behaviour is what adaptive behaviour
scales measure. The importance of the construct for diagnosis, intervention and
planning has been highlighted throughout the literature. It is recommended that
researchers and clinicians critically review what measures of adaptive behaviour
they are utilising and it is suggested that the definition and theory is
revisited.
PMID- 29342928
TI - Protein Oxidation and Sensory Quality of Brine-Injected Pork Loins Added
Ascorbate or Extracts of Green Tea or Mate during Chill-Storage in High-Oxygen
Modified Atmosphere.
AB - Background: Ascorbate is often applied to enhance stability and robustness of
brine-injected pork chops sold for retail, but may affect protein oxidation,
while plant extracts are potential substitutes. Methods: Brine-injected pork
chops (weight-gain ~12%, NaCl ~0.9%) prepared with ascorbate (225 ppm), green tea
extract (25 ppm gallic acid equivalents (GAE)), or mate extract (25 ppm GAE)
stored (5 degrees C, seven days) in high-oxygen atmosphere packaging (MAP: 80%
O2 and 20% CO2) were analyzed for color changes, sensory quality, and protein
oxidation compared to a control without antioxidant. Results: No significant
differences were observed for green tea and mate extracts as compared to
ascorbate when evaluated based on lipid oxidation derived off-flavors, except for
stale flavor, which mate significantly reduced. All treatments increased the
level of the protein oxidation product, alpha-aminoadipic semialdehyde as
compared to the control, and ascorbate was further found to increase thiol loss
and protein cross-linking, with a concomitant decrease in the sensory perceived
tenderness. Conclusions: Green tea and mate were found to equally protect against
lipid oxidation derived off-flavors, and mate showed less prooxidative activity
towards proteins as compared to ascorbate, resulting in more tender meat. Mate is
a valuable substitute for ascorbate in brine-injected pork chops.
PMID- 29342929
TI - Morphology-Controlled Synthesis of Hematite Nanocrystals and Their Optical,
Magnetic and Electrochemical Performance.
AB - A series of alpha-Fe2O3 nanocrystals (NCs) with fascinating morphologies, such as
hollow nanoolives, nanotubes, nanospindles, and nanoplates, were prepared through
a simple template-free hydrothermal synthesis process. The results showed that
the morphologies could be easily controlled by SO42- and H2PO4-. Physical
property analysis showed that the alpha-Fe2O3 NCs exhibited shape- and size
dependent ferromagnetic and optical behaviors. The absorption band peak of the
alpha-Fe2O3 NCs could be tuned from 320 to 610 nm. Furthermore, when applied as
electrode material for supercapacitor, the hollow olive-structure exhibited the
highest capacitance (285.9 F.g-1) and an excellent long-term cycling stability
(93% after 3000 cycles), indicating that it could serve as a candidate electrode
material for a supercapacitor.
PMID- 29342930
TI - Allergies in Animals and Humans.
AB - Allergy to inhalant and food allergens affects many patients worldwide [...].
PMID- 29342932
TI - Interstitial Glucose and Physical Exercise in Type 1 Diabetes: Integrative
Physiology, Technology, and the Gap In-Between.
AB - Continuous and flash glucose monitoring systems measure interstitial fluid
glucose concentrations within a body compartment that is dramatically altered by
posture and is responsive to the physiological and metabolic changes that enable
exercise performance in individuals with type 1 diabetes. Body fluid
redistribution within the interstitial compartment, alterations in interstitial
fluid volume, changes in rate and direction of fluid flow between the
vasculature, interstitium and lymphatics, as well as alterations in the rate of
glucose production and uptake by exercising tissues, make for caution when
interpreting device read-outs in a rapidly changing internal environment during
acute exercise. We present an understanding of the physiological and metabolic
changes taking place with acute exercise and detail the blood and interstitial
glucose responses with different forms of exercise, namely sustained endurance,
high-intensity, and strength exercises in individuals with type 1 diabetes.
Further, we detail novel technical information on currently available patient
devices. As more health services and insurance companies advocate their use,
understanding continuous and flash glucose monitoring for its strengths and
limitations may offer more confidence for patients aiming to manage glycemia
around exercise.
PMID- 29342931
TI - Transcriptome Analysis Based on RNA-Seq in Understanding Pathogenic Mechanisms of
Diseases and the Immune System of Fish: A Comprehensive Review.
AB - In recent years, with the advent of next-generation sequencing along with the
development of various bioinformatics tools, RNA sequencing (RNA-Seq)-based
transcriptome analysis has become much more affordable in the field of biological
research. This technique has even opened up avenues to explore the transcriptome
of non-model organisms for which a reference genome is not available. This has
made fish health researchers march towards this technology to understand
pathogenic processes and immune reactions in fish during the event of infection.
Recent studies using this technology have altered and updated the previous
understanding of many diseases in fish. RNA-Seq has been employed in the
understanding of fish pathogens like bacteria, virus, parasites, and oomycetes.
Also, it has been helpful in unraveling the immune mechanisms in fish.
Additionally, RNA-Seq technology has made its way for future works, such as
genetic linkage mapping, quantitative trait analysis, disease-resistant strain or
broodstock selection, and the development of effective vaccines and therapies.
Until now, there are no reviews that comprehensively summarize the studies which
made use of RNA-Seq to explore the mechanisms of infection of pathogens and the
defense strategies of fish hosts. This review aims to summarize the contemporary
understanding and findings with regard to infectious pathogens and the immune
system of fish that have been achieved through RNA-Seq technology.
PMID- 29342933
TI - In Vitro Anticoagulant Activity and Active Components of Safflower Injection.
AB - Safflower injection is well-known as a traditional Chinese medicine used to
improve the blood circulation. In this study, seven safflower injection samples
from different companies were evaluated for their in vitro anticoagulant activity
by measuring their activated partial thromboplastin time (APTT) and prothrombin
time (PT) against human plasma. The screening results suggested that the
safflower injections exhibited a significant prolonging influence on APTT (p <
0.05 vs. the control group), but not on prolonging PT (p > 0.05 vs. the control
group). The safflower injection was separated into four fractions, and among
them, fraction four demonstrated the most anticoagulant activity, with an APTT of
95.4 +/- 1.4 s at a concentration of 4.0 MUg/MUL (p < 0.01 vs. control group). In
addition, three active components, p-hydroxybenzaldehyde, p-hydroxy-cinnamic
acid, and (8Z)-decaene-4,6-diyne-1-O-beta-d-glucopyranoside were isolated from
fraction four with Sephadex LH-20 and C18 column chromatography. All three active
components showed significant prolonging of APTT (p < 0.05 vs. control group).
Among them, p-hydroxy-cinnamic acid exhibited the most activity (p < 0.01 vs.
control group). The results indicated that safflower injection strongly affects
the intrinsic coagulation system, and we suggest that this might be the mechanism
by which the safflower injection activates and promotes blood circulation.
PMID- 29342934
TI - Exploring Positive Survivorship Experiences of Indigenous Australian Cancer
Patients.
AB - Amongst Indigenous Australians, "cancer" has negative connotations that
detrimentally impact upon access to cancer care services. Barriers to accessing
cancer services amongst Indigenous Australians are widely reported. In contrast,
factors that facilitate this cohort to successfully navigate cancer care services
("enablers") are scarcely reported in the literature. Through qualitative
interviews, this article examines factors that assist Indigenous Australians to
have positive cancer experiences. Semi-structured interviews were conducted with
twelve adult Indigenous oncology patients recruited from a tertiary hospital in
Queensland, Australia during 2012-2014. Data generated from the interviews were
independently reviewed by two researchers via inductive thematic analytical
processes. Discussions followed by consensus on the major categories allowed
conclusions to be drawn on potential enablers. Two major categories of enablers
were identified by the researchers: resilience and communication. Individual's
intrinsic strength, their coping strategies, and receipt of support improved
participant's resilience and consequently supported a positive experience.
Communication methods and an effective patient-provider relationship facilitated
positive experiences for participants. Despite potential barriers to access of
care for Indigenous cancer patients, participants in the study demonstrated that
it was still possible to focus on the positive aspects of their cancer
experiences. Many participants explained how cancer changed their outlook on
life, often for the better, with many feeling empowered as they progressed
through their cancer diagnosis and treatment processes.
PMID- 29342935
TI - Exogenous Melatonin Alleviates Cold Stress by Promoting Antioxidant Defense and
Redox Homeostasis in Camellia sinensis L.
AB - The unprecedented early spring frost that appears as a cold stress adversely
affects growth and productivity in tea (Camellia sinensis L.); therefore, it is
indispensable to develop approaches to improve the cold tolerance of tea. Here,
we investigated the effect of pretreatment with exogenous melatonin on the net
photosynthetic rate, the maximum photochemical efficiency of PSII, chlorophyll
content, lipid peroxidation, reactive oxygen species (ROS) accumulation,
antioxidant potential, and redox homeostasis in leaves of tea plants following
cold stress. Our results revealed that cold treatment induced oxidative stress by
increasing ROS accumulation, which in turn affected the photosynthetic process in
tea leaves. However, treatment with melatonin mitigated cold-induced reductions
in photosynthetic capacity by reducing oxidative stress through enhanced
antioxidant potential and redox homeostasis. This study provides strong evidence
that melatonin could alleviate cold-induced adverse effects in tea plants.
PMID- 29342936
TI - Structure Characterization of Honey-Processed Astragalus Polysaccharides and Its
Anti-Inflammatory Activity In Vitro.
AB - Honey-processed Astragalus is a dosage form of Radix Astragalus mixed with honey
by a traditional Chinese medicine processing method which strengthens the tonic
effect. Astragalus polysaccharide (APS), perform its immunomodulatory effects by
relying on the tonic effect of Radix Astragalus, therefore, the improved
pharmacological activity of honey-processed Astragalus polysaccharide (HAPS)
might be due to structural changes during processing. The molecular weights of
HAPS and APS were 1,695,788 Da, 2,047,756 Da, respectively, as determined by high
performance gel filtration chromatography combined with evaporative light
scattering detection (HPGFC-ELSD). The monosaccharide composition was determined
by ultra-performance liquid chromatogram quadrupole time-of-flight mass
spectrometry (UPLC/ESI-Q-TOF-MS) after pre-column derivatization with 1-phenyl-3
methyl-5-pyrazolone (PMP). The results showed that the essential components were
mannose, glucose, xylose, arabinose, glucuronic acid and rhamnose, is molar
ratios of 0.06:28.34:0.58:0.24:0.33:0.21 and 0.27:12.83:1.63:0.71:1.04:0.56,
respectively. FT-IR and NMR analysis of HAPS results showed the presence of
uronic acid and acetyl groups. The anti-inflammatory activities of HAPS were more
effective than those of APS according to the NO contents and the expression of
IFN-gamma, IL-1beta, IL-22 and TNF-alpha in lipopolysaccharide (LPS)-induced
RAW264.7 cells. This findings suggest that the anti-inflammatory and bioactivity
improvement might be associated with molecular structure changes, bearing on the
potential immunomodulatory action.
PMID- 29342937
TI - Does a High Sugar High Fat Dietary Pattern Explain the Unequal Burden in
Prevalence of Type 2 Diabetes in a Multi-Ethnic Population in The Netherlands?
The HELIUS Study.
AB - The risk for type 2 diabetes (T2D) in ethnic minorities in Europe is higher in
comparison with their European host populations. The western dietary pattern,
characterized by high amounts of sugar and saturated fat (HSHF dietary pattern),
has been associated with a higher risk for T2D. Information on this association
in minority populations is scarce. Therefore, we aimed to investigate the HSHF
dietary pattern and its role in the unequal burden of T2D prevalence in a multi
ethnic population in The Netherlands. We included 4694 participants aged 18-70
years of Dutch, South-Asian Surinamese, African Surinamese, Turkish, and Moroccan
origin from the HELIUS study. Dutch participants scored the highest on the HSHF
dietary pattern, followed by the Turkish, Moroccan, African Surinamese, and South
Asian Surinamese participants. Prevalence ratios (PR) for T2D were then
calculated using multivariate cox regression analyses, adjusted for
sociodemographic, anthropometric, and lifestyle factors. Higher adherence to an
HSHF diet was not significantly related to T2D prevalence in the total study
sample (PR 1.04 high versus low adherence, 95% CI: 0.80-1.35). In line,
adjustment for HSHF diet score did not explain the ethnic differences in T2D. For
instance, the PR of the South-Asian Surinamese vs. Dutch changed from 2.76 (95%
CI: 2.05-3.72) to 2.90 (95% CI: 2.11-3.98) after adjustment for HSHF. To
conclude, a western dietary pattern high in sugar and saturated fat was not
associated with T2D, and did not explain the unequal burden in prevalence of T2D
across the ethnic groups.
PMID- 29342938
TI - Role of Aquaporins in Determining Carbon and Nitrogen Status in Higher Plants.
AB - Aquaporins (AQPs) are integral membrane proteins facilitating the transport of
water and some small neutral molecules across cell membranes. In past years, much
effort has been made to reveal the location of AQPs as well as their function in
water transport, photosynthetic processes, and stress responses in higher plants.
In the present review, we paid attention to the character of AQPs in determining
carbon and nitrogen status. The role of AQPs during photosynthesis is
characterized as its function in transporting water and CO2 across the membrane
of chloroplast and thylakoid; recalculated results from published studies showed
that over-expression of AQPs contributed to 25% and 50% increases in stomatal
conductance (gs) and mesophyll conductance (gm), respectively. The nitrogen
status in plants is regulated by AQPs through their effect on water flow as well
as urea and NH4+ uptake, and the potential role of AQPs in alleviating ammonium
toxicity is discussed. At the same time, root and/or shoot AQP expression is
quite dependent on both N supply amounts and forms. Future research directions
concerning the function of AQPs in regulating plant carbon and nitrogen status as
well as C/N balance are also highlighted.
PMID- 29342939
TI - Deciphering the Evolution and Development of the Cuticle by Studying Lipid
Transfer Proteins in Mosses and Liverworts.
AB - When plants conquered land, they developed specialized organs, tissues, and cells
in order to survive in this new and harsh terrestrial environment. New cell
polymers such as the hydrophobic lipid-based polyesters cutin, suberin, and
sporopollenin were also developed for protection against water loss, radiation,
and other potentially harmful abiotic factors. Cutin and waxes are the main
components of the cuticle, which is the waterproof layer covering the epidermis
of many aerial organs of land plants. Although the in vivo functions of the group
of lipid binding proteins known as lipid transfer proteins (LTPs) are still
rather unclear, there is accumulating evidence suggesting a role for LTPs in the
transfer and deposition of monomers required for cuticle assembly. In this
review, we first present an overview of the data connecting LTPs with cuticle
synthesis. Furthermore, we propose liverworts and mosses as attractive model
systems for revealing the specific function and activity of LTPs in the
biosynthesis and evolution of the plant cuticle.
PMID- 29342942
TI - A Sensor Dynamic Measurement Error Prediction Model Based on NAPSO-SVM.
AB - Dynamic measurement error correction is an effective way to improve sensor
precision. Dynamic measurement error prediction is an important part of error
correction, and support vector machine (SVM) is often used for predicting the
dynamic measurement errors of sensors. Traditionally, the SVM parameters were
always set manually, which cannot ensure the model's performance. In this paper,
a SVM method based on an improved particle swarm optimization (NAPSO) is proposed
to predict the dynamic measurement errors of sensors. Natural selection and
simulated annealing are added in the PSO to raise the ability to avoid local
optima. To verify the performance of NAPSO-SVM, three types of algorithms are
selected to optimize the SVM's parameters: the particle swarm optimization
algorithm (PSO), the improved PSO optimization algorithm (NAPSO), and the
glowworm swarm optimization (GSO). The dynamic measurement error data of two
sensors are applied as the test data. The root mean squared error and mean
absolute percentage error are employed to evaluate the prediction models'
performances. The experimental results show that among the three tested
algorithms the NAPSO-SVM method has a better prediction precision and a less
prediction errors, and it is an effective method for predicting the dynamic
measurement errors of sensors.
PMID- 29342941
TI - Development of Optical Fiber Based Measurement System for the Verification of
Entrance Dose Map in Pencil Beam Scanning Proton Beam.
AB - This study describes the development of a beam monitoring system for the
verification of entrance dose map in pencil beam scanning (PBS) proton therapy
based on fiber optic radiation sensors (FORS) and the validation of this system
through a feasibility study. The beam monitoring system consisted of 128 optical
fibers optically coupled to photo-multiplier tubes. The performance of the beam
monitoring system based on FORS was verified by comparing 2D dose maps of square
shaped fields of various sizes, which were obtained using conventional dosimeters
such as MatriXX and EBT3 film, with those measured using FORS. The resulting full
width at half maximum and penumbra were compared for PBS proton beams, with a
<=2% difference between each value, indicating that measurements using the
conventional dosimetric tool corresponded to measurements based on FORS. For
irregularly-shaped fields, a comparison based on the gamma index between 2D dose
maps obtained using MatriXX and EBT3 film and the 2D dose map measured by the
FORS showed passing rates of 96.9 +/- 1.3% and 96.2 +/- 1.9%, respectively,
confirming that FORS-based measurements for PBS proton therapy agreed well with
those measured using the conventional dosimetric tools. These results demonstrate
that the developed beam monitoring system based on FORS is good candidate for
monitoring the entrance dose map in PBS proton therapy.
PMID- 29342940
TI - Deoxyschizandrin, Isolated from Schisandra Berries, Induces Cell Cycle Arrest in
Ovarian Cancer Cells and Inhibits the Protumoural Activation of Tumour-Associated
Macrophages.
AB - Deoxyschizandrin, a major lignan of Schisandra berries, has been demonstrated to
have various biological activities such as antioxidant, hepatoprotective, and
antidiabetic effects. However, the anti-cancer effects of deoxyschizandrin are
poorly characterized. In the present study, we investigated the anti-cancer
effect of deoxyschizandrin on human ovarian cancer cell lines and tumour
associated macrophages (TAMs). Deoxyschizandrin induced G0/G1 phase cell cycle
arrest and inhibited cyclin E expression in human ovarian cancer cells.
Overexpression of cyclin E significantly reversed the deoxyschizandrin-induced
cell growth inhibition. Interestingly, increased production of reactive oxygen
species and decreased activation of Akt were observed in A2780 cells treated with
deoxyschizandrin, and the antioxidant compromised the deoxyschizandrin-induced
cell growth inhibition and Akt inactivation. Moreover, deoxyschizandrin-induced
cell growth inhibition was markedly suppressed by Akt overexpression. In
addition, deoxyschizandrin was found to inhibit the expression of the M2
phenotype markers CD163 and CD209 in TAMs, macrophages stimulated by the ovarian
cancer cells. Moreover, expression and production of the tumour-promoting factors
MMP-9, RANTES, and VEGF, which are highly enhanced in TAMs, was significantly
suppressed by deoxyschizandrin treatment. Taken together, these data suggest that
deoxyschizandrin exerts anti-cancer effects by inducing G0/G1 cell cycle arrest
in ovarian cancer cells and reducing the protumoural phenotype of TAMs.
PMID- 29342943
TI - The Peptide PnPP-19, a Spider Toxin Derivative, Activates MU-Opioid Receptors and
Modulates Calcium Channels.
AB - The synthetic peptide PnPP-19 comprehends 19 amino acid residues and it
represents part of the primary structure of the toxin delta-CNTX-Pn1c (PnTx2-6),
isolated from the venom of the spider Phoneutria nigriventer. Behavioural tests
suggest that PnPP-19 induces antinociception by activation of CB1, MU and delta
opioid receptors. Since the peripheral and central antinociception induced by
PnPP-19 involves opioid activation, the aim of this work was to identify whether
this synthetic peptide could directly activate opioid receptors and investigate
the subtype selectivity for MU-, delta- and/or kappa-opioid receptors.
Furthermore, we also studied the modulation of calcium influx driven by PnPP-19
in dorsal root ganglion neurons, and analyzed whether this modulation was opioid
mediated. PnPP-19 selectively activates MU-opioid receptors inducing indirectly
inhibition of calcium channels and hereby impairing calcium influx in dorsal root
ganglion (DRG) neurons. Interestingly, notwithstanding the activation of opioid
receptors, PnPP-19 does not induce beta-arrestin2 recruitment. PnPP-19 is the
first spider toxin derivative that, among opioid receptors, selectively activates
MU-opioid receptors. The lack of beta-arrestin2 recruitment highlights its
potential for the design of new improved opioid agonists.
PMID- 29342944
TI - A Novel Adaptive Modulation Based on Nondata-Aided Error Vector Magnitude in Non
Line-Of-Sight Condition of Wireless Sensor Network.
AB - The high demand for multimedia applications in environmental monitoring, invasion
detection, and disaster aid has led to the rise of wireless sensor network (WSN).
With the increase of reliability and diversity of information streams, the higher
requirements on throughput and quality of service (QoS) have been put forward in
data transmission between two sensor nodes. However, lower spectral efficiency
becomes a bottleneck in non-line-of-sight (NLOS) transmission of WSN. This paper
proposes a novel nondata-aided error vector magnitude based adaptive modulation
(NDA-EVM-AM) to solve the problem. NDA-EVM is considered as a new metric to
evaluate the quality of NLOS link for adaptive modulation in WSN. By modeling the
NLOS scenario as the eta - MU fading channel, a closed-form expression for the
NDA-EVM of multilevel quadrature amplitude modulation (MQAM) signals over the eta
- MU fading channel is derived, and the relationship between SER and NDA-EVM is
also formulated. Based on these results, NDA-EVM state machine is designed for
adaptation strategy. The algorithmic complexity of NDA-EVM-AM is analyzed and the
outage capacity of NDA-EVM-AM in an NLOS scenario is also given. The performances
of NDA-EVM-AM are compared by simulation, and the results show that NDA-EVM-AM is
an effective technique to be used in the NLOS scenarios of WSN. This technique
can accurately reflect the channel variations and efficiently adjust modulation
order to better match the channel conditions, hence, obtaining better performance
in average spectral efficiency.
PMID- 29342945
TI - Hyperspectral Features of Oil-Polluted Sea Ice and the Response to the
Contamination Area Fraction.
AB - Researchers have studied oil spills in open waters using remote sensors, but few
have focused on extracting reflectance features of oil pollution on sea ice. An
experiment was conducted on natural sea ice in Bohai Bay, China, to obtain the
spectral reflectance of oil-contaminated sea ice. The spectral absorption index
(SAI), spectral peak height (SPH), and wavelet detail coefficient (DWT d5) were
calculated using stepwise multiple linear regression. The reflectances of some
false targets were measured and analysed. The simulated false targets were
sediment, iron ore fines, coal dust, and the melt pool. The measured reflectances
were resampled using five common sensors (GF-2, Landsat8-OLI, Sentinel3-OLCI,
MODIS, and AVIRIS). Some significant spectral features could discriminate between
oil-polluted and clean sea ice. The indices correlated well with the oil area
fractions. All of the adjusted R2 values exceeded 0.9. The SPH model1, based on
spectral features at 507-670 and 1627-1746 nm, displayed the best fitting. The
resampled data indicated that these multi-spectral and hyper-spectral sensors
could be used to detect crude oil on the sea ice if the effect of noise and
spatial resolution are neglected. The spectral features and their identified
changes may provide reference on sensor design and band selection.
PMID- 29342946
TI - Effects of Alloying Elements on the Formation of Core-Shell-Structured
Reinforcing Particles during Heating of Al-Ti Powder Compacts.
AB - To prepare core-shell-structured Ti@compound particle (Ti@compoundp) reinforced
Al matrix composite via powder thixoforming, the effects of alloying elements,
such as Si, Cu, Mg, and Zn, on the reaction between Ti powders and Al melt, and
the microstructure of the resulting reinforcements were investigated during
heating of powder compacts at 993 K (720 degrees C). Simultaneously, the
situations of the reinforcing particles in the corresponding semisolid compacts
were also studied. Both thermodynamic analysis and experiment results all
indicate that Si participated in the reaction and promoted the formation of Al-Ti
Si ternary compounds, while Cu, Mg, and Zn did not take part in the reaction and
facilitated Al3Ti phase to form to different degrees. The first-formed Al-Ti-Si
ternary compound was tau1 phase, and then it gradually transformed into
(Al,Si)3Ti phase. The proportion and existing time of tau1 phase all increased as
the Si content increased. In contrast, Mg had the largest, Cu had the least, and
Si and Zn had an equivalent middle effect on accelerating the reaction. The
thicker the reaction shell was, the larger the stress generated in the shell was,
and thus the looser the shell microstructure was. The stress generated in
(Al,Si)3Ti phase was larger than that in tau1 phase, but smaller than that in
Al3Ti phase. So, the shells in the Al-Ti-Si system were more compact than those
in the other systems, and Si element was beneficial to obtain thick and compact
compound shells. Most of the above results were consistent to those in the
semisolid state ones except the product phase constituents in the Al-Ti-Mg system
and the reaction rate in the Al-Ti-Zn system. More importantly, the desirable
core-shell structured Ti@compoundp was only achieved in the semisolid Al-Ti-Si
system.
PMID- 29342947
TI - Understanding Tail-Biting in Pigs through Social Network Analysis.
AB - The objective of this study was to investigate the association between social
structure and incidence of tail-biting in pigs. Pigs (n = 144, initial weight =
7.2 +/- 1.57 kg, 4 weeks of age) were grouped based on their litter origin:
littermates, non-littermates, and half-group of littermates. Six pens (8
pigs/pen) of each litter origin were studied for 6 weeks. Incidence of tail
injury and growth performance were monitored. Behavior of pigs was video recorded
for 6 h at 6 and 8 weeks of age. Video recordings were scanned at 10 min
intervals to register pigs that were lying together (1) or not (0) in binary
matrices. Half weight association index was used for social network construction.
Social network analysis was performed using the UCINET software. Littermates had
lower network density (0.119 vs. 0.174; p < 0.05), more absent social ties (20
vs. 12; p < 0.05), and fewer weak social ties (6 vs. 14, p < 0.05) than non
littermates, indicating that littermates might be less socially connected.
Fifteen percent of littermates were identified as victimized pigs by tail-biting,
and no victimized pigs were observed in other treatment groups. These results
suggest that littermates might be less socially connected among themselves which
may predispose them to development of tail-biting.
PMID- 29342948
TI - Micro-Structures and High-Temperature Friction-Wear Performances of Laser Cladded
Cr-Ni Coatings.
AB - Cr-Ni coatings with the mass ratios of 17% Cr-83% Ni, 20% Cr-80% Ni and 24% Cr
76% Ni were fabricated on H13 hot work mould steel using a laser cladding (LC).
The surface-interface morphologies, chemical elements, surface roughness and
phase composition of the obtained Cr-Ni coatings were analysed using a scanning
electron microscope (SEM), energy disperse spectroscopy (EDS), atomic force
microscope (AFM) and X-ray diffractometer (XRD), respectively. The friction-wear
properties and wear rates of Cr-Ni coatings with the different mass ratios of Cr
and Ni at 600 degrees C were investigated, and the worn morphologies and wear
mechanism of Cr-Ni coatings were analysed. The results show that the phases of Cr
Ni coatings with mass ratios of 17% Cr-83% Ni, 20% Cr-80% Ni and 24% Cr-76% Ni
are composed of Cr + Ni single-phases and their compounds at the different
stoichiometry, the porosities on the Cr-Ni coatings increase with the Cr content
increasing. The average coefficient of friction (COF) of 17% Cr-83% Ni, 20% Cr
80% Ni and 24% Cr-76% coatings are 1.10, 0.33 and 0.87, respectively, in which
the average COF of 20% Cr-80% Ni coating is the lowest, exhibiting the better
anti-friction performance. The wear rate of 17% Cr-83% Ni, 20% Cr-80% Ni and 24%
Cr-76% Ni coatings is 4.533 * 10-6, 5.433 * 10-6, and 1.761 * 10-6 N-1.s-1,
respectively, showing the wear resistance of Cr-Ni coatings at a high temperature
increases with the Cr content, in which the wear rate is 24% Cr-76% Ni coating
with the better reducing wear. The wear mechanism of 17% Cr-83% Ni and 20% Cr-80%
Ni and 24% Cr-76% coatings at 600 degrees C is primarily adhesive wear, and that
of 24% Cr-76% coating is also accompanied by oxidative wear.
PMID- 29342951
TI - Microstructure and Tensile Properties of ECAPed Mg-9Al-1Si-1SiC Composites: The
Influence of Initial Microstructures.
AB - Mg-9Al-1Si-1SiC composites with various initial microstructures prior to equal
channel angular pressing (ECAP) were obtained by different pre-treatments
(without and with homogenization treatment), and the resultant grain size, second
phase and tensile properties of ECAPed composites were reported. The ECAPed
composite with homogenization treatment (HT) exhibited finer grain size, higher
fraction of dynamically recrystallized (DRXed) grains, weaker texture intensity,
as well as the presence of dynamic precipitated Mg17Al12 phase compared to that
without HT. Besides, the morphology of pre-existing Mg2Si changed from massive
like to needle-like in the ECAPed composite with HT. Room-temperature tensile
test results showed that ultimate tensile strength (UTS), yield strength (YS),
and elongation (El) of ECAPed composites with HT were 16.1%, 23%, and 27.3%
larger than that without HT, respectively.
PMID- 29342950
TI - Recent Advances of Rare-Earth Ion Doped Luminescent Nanomaterials in Perovskite
Solar Cells.
AB - Organic-inorganic lead halide based perovskite solar cells have received broad
interest due to their merits of low fabrication cost, a low temperature solution
process, and high energy conversion efficiencies. Rare-earth (RE) ion doped
nanomaterials can be used in perovskite solar cells to expand the range of
absorption spectra and improve the stability due to its upconversion and
downconversion effect. This article reviews recent progress in using RE-ion-doped
nanomaterials in mesoporous electrodes, perovskite active layers, and as an
external function layer of perovskite solar cells. Finally, we discuss the
challenges facing the effective use of RE-ion-doped nanomaterials in perovskite
solar cells and present some prospects for future research.
PMID- 29342949
TI - Characterization of a Novel Alginate Lyase from Marine Bacterium Vibrio furnissii
H1.
AB - Alginate lyases show great potential for industrial and medicinal applications,
especially as an attractive biocatalyst for the production of oligosaccharides
with special bioactivities. A novel alginate lyase, AlyH1, from the marine
bacterium Vibrio furnissii H1, which has been newly isolated from rotten seaweed,
was purified and characterized. The purified enzyme showed the specific activity
of 2.40 U/mg. Its molecular mass was 35.8 kDa. The optimal temperature and pH
were 40 degrees C and pH 7.5, respectively. AlyH1 maintained stability at
neutral pH (7.0-8.0) and temperatures below 30 degrees C. Metal ions Na+, Mg2+,
and K+ increased the activity of the enzyme. With sodium alginate as the
substrate, the Km and Vmax values of AlyH1 were 2.28 mg/mL and 2.81 U/mg,
respectively. AlyH1 exhibited activities towards both polyguluronate and
polymannuronate, and preferentially degraded polyguluronate. Products prepared
from sodium alginate by AlyH1 were displayed to be di-, tri-, and tetra-alginate
oligosaccharides. A partial amino acid sequence (190 aa) of AlyH1 analysis
suggested that AlyH1 was an alginate lyase of polysaccharide lyase family 7. The
sequence showed less than 77% identity to the reported alginate lyases. These
data demonstrated that AlyH1 could be as a novel and potential candidate in
application of alginate oligosaccharides production with low polymerization
degrees.
PMID- 29342952
TI - A Long-Term Follow-Up of the Efficacy of Nature-Based Therapy for Adults
Suffering from Stress-Related Illnesses on Levels of Healthcare Consumption and
Sick-Leave Absence: A Randomized Controlled Trial.
AB - Stress-related illnesses are a growing health problem in the Western world; which
also has economic significance for society. As a consequence; there is a growing
demand for effective treatments. The study investigates the long-term efficacy of
the Nacadia(r) nature-based therapy (NNBT) by comparing it to the efficacy of a
validated cognitive behavioral therapy, called STreSS. The study is designed as a
randomized controlled trial in which 84 participants are randomly allocated
between the treatments. Long-term efficacy is investigated through data extracts
from the national database of Statistics Denmark on the sick leave and the health
care consumption. The results show that both the NNBT and the STreSS lead to a
significant decrease in number of contacts with a general practitioner in the
period from twelve months prior to treatment to twelve months after treatment;
and, a significant decrease in long-term sick leave from the month prior to
treatment to twelve months after treatment. The positive long-term effects
provide validation for the NNBT as an efficient treatment of stress-related
illnesses.
PMID- 29342953
TI - Review of Recent Metamaterial Microfluidic Sensors.
AB - Metamaterial elements/arrays exhibit a sensitive response to fluids yet with a
small footprint, therefore, they have been an attractive choice to realize
various sensing devices when integrated with microfluidic technology. Micro
channels made from inexpensive biocompatible materials avoid any contamination
from environment and require only microliter-nanoliter sample for sensing. Simple
design, easy fabrication process, light weight prototype, and instant
measurements are advantages as compared to conventional (optical, electrochemical
and biological) sensing systems. Inkjet-printed flexible sensors find their
utilization in rapidly growing wearable electronics and health-monitoring
flexible devices. Adequate sensitivity and repeatability of these low profile
microfluidic sensors make them a potential candidate for point-of-care testing
which novice patients can use reliably. Aside from degraded sensitivity and lack
of selectivity in all practical microwave chemical sensors, they require an
instrument, such as vector network analyzer for measurements and not readily
available as a self-sustained portable sensor. This review article presents state
of-the-art metamaterial inspired microfluidic bio/chemical sensors (passive
devices ranging from gigahertz to terahertz range) with an emphasis on
metamaterial sensing circuit and microfluidic detection. We also highlight
challenges and strategies to cope these issues which set future directions.
PMID- 29342954
TI - A Built-In CpG Adjuvant in RSV F Protein DNA Vaccine Drives a Th1 Polarized and
Enhanced Protective Immune Response.
AB - Human respiratory syncytial virus (RSV) is the most significant cause of acute
lower respiratory infection in children. However, there is no licensed vaccine
available. Here, we investigated the effect of five or 20 copies of C-Class of
CpG ODN (CpG-C) motif incorporated into a plasmid DNA vaccine encoding RSV fusion
(F) glycoprotein on the vaccine-induced immune response. The addition of CpG-C
motif enhanced serum binding and virus-neutralizing antibody responses in BALB/c
mice immunized with the DNA vaccines. Moreover, mice vaccinated with CpG-modified
vaccines, especially with the higher 20 copies, resulted in an enhanced shift
toward a Th1-biased antibody and T-cell response, a decrease in pulmonary
pathology and virus replication, and a decrease in weight loss after RSV
challenge. This study suggests that CpG-C motif, cloned into the backbone of DNA
vaccine encoding RSV F glycoprotein, functions as a built-in adjuvant capable of
improving the efficacy of DNA vaccine against RSV infection.
PMID- 29342956
TI - Development of a Scale-up Tool for Pervaporation Processes.
AB - In this study, an engineering tool for the design and optimization of
pervaporation processes is developed based on physico-chemical modelling coupled
with laboratory/mini-plant experiments. The model incorporates the solution
diffusion-mechanism, polarization effects (concentration and temperature), axial
dispersion, pressure drop and the temperature drop in the feed channel due to
vaporization of the permeating components. The permeance, being the key model
parameter, was determined via dehydration experiments on a mini-plant scale for
the binary mixtures ethanol/water and ethyl acetate/water. A second set of
experimental data was utilized for the validation of the model for two chemical
systems. The industrially relevant ternary mixture, ethanol/ethyl acetate/water,
was investigated close to its azeotropic point and compared to a simulation
conducted with the determined binary permeance data. Experimental and simulation
data proved to agree very well for the investigated process conditions. In order
to test the scalability of the developed engineering tool, large-scale data from
an industrial pervaporation plant used for the dehydration of ethanol was
compared to a process simulation conducted with the validated physico-chemical
model. Since the membranes employed in both mini-plant and industrial scale were
of the same type, the permeance data could be transferred. The comparison of the
measured and simulated data proved the scalability of the derived model.
PMID- 29342955
TI - Pharmacokinetics of Schizandrin and Its Pharmaceutical Products Assessed Using a
Validated LC-MS/MS Method.
AB - Schisandra chinensis has been used as an important component in various
prescriptions in traditional Chinese medicine and, more recently, in Western
based medicine for its anti-hepatotoxic effect. The aim of this study was to
develop a selective, rapid, and sensitive ultra-performance liquid chromatography
tandem mass spectrometry method for pharmacokinetic studies of schizandrin in
rats. Liquid-liquid extraction was used for plasma sample preparation. A UHPLC
reverse-phase C18e column (100 mm * 2.1 mm, 2 MUm) coupled with a mobile phase of
methanol-0.1% formic acid (85:15, v/v) was used for sample separation. A triple
quadrupole tandem mass spectrometer was used to detect the analytes in the
selected reaction monitoring mode. The linear range of schizandrin in rat plasma
was 5.0-1000 ng/mL (r2 > 0.999), with a lower limit of quantification of 5 ng/mL.
The method was validated with regard to accuracy, intra-day and inter-day
precision, linearity, stability, recovery, and matrix effects in rat plasma,
which were acceptable according to the biological method validation guidelines
developed by the FDA. This method was successfully applied to a pharmacokinetic
study after oral administration of 3 g/kg and 10 g/kg of Schisandra chinensis
products, which yielded a maximum concentration of schizandrin of 0.08 +/- 0.07
and 0.15 +/- 0.09 MUg/mL, respectively. A parallel study design was used to
investigate the oral bioavailability of single compound of schizandrin and the
herbal extract, the single compound of pure schizandrin (10 mg/kg, i.v.), pure
schizandrin (10 mg/kg, p.o.), and the herbal extract of Schisandra chinensis (3
g/kg and 10 g/kg, p.o.) were given individually. The dose of Schisandra chinensis
(3 g/kg) equivalent to schizandrin (5.2 mg/kg); the dose of Schisandra chinensis
(10 g/kg) equivalent to schizandrin (17.3 mg/kg). The result demonstrated that
the oral bioavailability of schizandrin was approximately 15.56 +/- 10.47% in
rats, however the oral bioavailability of herbal extract was higher than single
compound. The method was successfully applied to the pharmacokinetic study of
pure schizandrin after oral administration of its pharmaceutical industry
products in rats.
PMID- 29342957
TI - Comparative Transcriptome Analysis Identifies Putative Genes Involved in Steroid
Biosynthesis in Euphorbia tirucalli.
AB - Phytochemical analysis of different Euphorbia tirucalli tissues revealed a
contrasting tissue-specificity for the biosynthesis of euphol and beta
sitosterol, which represent the two pharmaceutically active steroids in E.
tirucalli. To uncover the molecular mechanism underlying this tissue-specificity
for phytochemicals, a comprehensive E. tirucalli transcriptome derived from its
root, stem, leaf and latex was constructed, and a total of 91,619 unigenes were
generated with 51.08% being successfully annotated against the non-redundant (Nr)
protein database. A comparison of the transcriptome from different tissues
discovered members of unigenes in the upstream steps of sterol backbone
biosynthesis leading to this tissue-specific sterol biosynthesis. Among them, the
putative oxidosqualene cyclase (OSC) encoding genes involved in euphol synthesis
were notably identified, and their expressions were significantly up-regulated in
the latex. In addition, genome-wide differentially expressed genes (DEGs) in the
different E. tirucalli tissues were identified. The cluster analysis of those
DEGs showed a unique expression pattern in the latex compared with other tissues.
The DEGs identified in this study would enrich the insights of sterol
biosynthesis and the regulation mechanism of this latex-specificity.
PMID- 29342958
TI - An Enhanced Method to Estimate Heart Rate from Seismocardiography via Ensemble
Averaging of Body Movements at Six Degrees of Freedom.
AB - Continuous cardiac monitoring has been developed to evaluate cardiac activity
outside of clinical environments due to the advancement of novel instruments.
Seismocardiography (SCG) is one of the vital components that could develop such a
monitoring system. Although SCG has been presented with a lower accuracy, this
novel cardiac indicator has been steadily proposed over traditional methods such
as electrocardiography (ECG). Thus, it is necessary to develop an enhanced method
by combining the significant cardiac indicators. In this study, the six-axis
signals of accelerometer and gyroscope were measured and integrated by the L2
normalization and multi-dimensional kineticardiography (MKCG) approaches,
respectively. The waveforms of accelerometer and gyroscope were standardized and
combined via ensemble averaging, and the heart rate was calculated from the
dominant frequency. Thirty participants (15 females) were asked to stand or sit
in relaxed and aroused conditions. Their SCG was measured during the task. As a
result, proposed method showed higher accuracy than traditional SCG methods in
all measurement conditions. The three main contributions are as follows: (1) the
ensemble averaging enhanced heart rate estimation with the benefits of the six
axis signals; (2) the proposed method was compared with the previous SCG method
that employs fewer-axis; and (3) the method was tested in various measurement
conditions for a more practical application.
PMID- 29342960
TI - A Low-Cost Inkjet-Printed Aptamer-Based Electrochemical Biosensor for the
Selective Detection of Lysozyme.
AB - Recently, inkjet-printing has gained increased popularity in applications such as
flexible electronics and disposable sensors, as well as in wearable sensors
because of its multifarious advantages. This work presents a novel, low-cost
immobilization technique using inkjet-printing for the development of an aptamer
based biosensor for the detection of lysozyme, an important biomarker in various
disease diagnosis. The strong affinity between the carbon nanotube (CNT) and the
single-stranded DNA is exploited to immobilize the aptamers onto the working
electrode by printing the ink containing the dispersion of CNT-aptamer complex.
The inkjet-printing method enables aptamer density control, as well as high
resolution patternability. Our developed sensor shows a detection limit of 90
ng/mL with high target selectivity against other proteins. The sensor also
demonstrates a shelf-life for a reasonable period. This technology has potential
for applications in developing low-cost point-of-care diagnostic testing kits for
home healthcare.
PMID- 29342959
TI - Structural Insights in Multifunctional Papillomavirus Oncoproteins.
AB - Since their discovery in the mid-eighties, the main papillomavirus oncoproteins
E6 and E7 have been recalcitrant to high-resolution structure analysis. However,
in the last decade a wealth of three-dimensional information has been gained on
both proteins whether free or complexed to host target proteins. Here, we first
summarize the diverse activities of these small multifunctional oncoproteins.
Next, we review the available structural data and the new insights they provide
about the evolution of E6 and E7, their multiple interactions and their
functional variability across human papillomavirus (HPV) species.
PMID- 29342961
TI - Effects of Salt Stress on Plant Growth, Antioxidant Capacity, Glandular Trichome
Density, and Volatile Exudates of Schizonepeta tenuifolia Briq.
AB - Salinity is a major abiotic factor affecting plant growth and secondary
metabolism. However, no information is available about its effects on
Schizonepeta tenuifolia Briq., a traditional Chinese herb. Here, we investigated
the changes of plant growth, antioxidant capacity, glandular trichome density,
and volatile exudates of S. tenuifolia exposed to salt stress (0, 25, 50, 75, 100
mM NaCl). Results showed that its dry biomass was reduced by salt treatments
except 25 mM NaCl. Contents of antioxidants, including phenolics and flavonoids,
increased at low (25 mM) or moderate (50 mM) levels, but declined at severe (75
and 100 mM) levels. On leaf surfaces, big peltate and small capitate glandular
trichomes (GTs) were found. Salt treatments, especially at moderate and severe
concentrations, enhanced the density of total GTs on both leaf sides. The most
abundant compound in GT volatile exudates was pulegone. Under salinity, relative
contents of this component and other monoterpenes decreased significantly;
biosynthesis and accumulation of esters were enhanced, particularly sulfurous
acid,2-ethylhexyl hexyl ester, which became the second major compound as salinity
increased. In conclusion, salt stress significantly influenced the growth and
secondary metabolism of S. tenuifolia, enabling us to study the changes of its
pharmacological activities.
PMID- 29342963
TI - Sum of the Magnitude for Hard Decision Decoding Algorithm Based on Loop Update
Detection.
AB - In order to improve the performance of non-binary low-density parity check codes
(LDPC) hard decision decoding algorithm and to reduce the complexity of decoding,
a sum of the magnitude for hard decision decoding algorithm based on loop update
detection is proposed. This will also ensure the reliability, stability and high
transmission rate of 5G mobile communication. The algorithm is based on the hard
decision decoding algorithm (HDA) and uses the soft information from the channel
to calculate the reliability, while the sum of the variable nodes' (VN) magnitude
is excluded for computing the reliability of the parity checks. At the same time,
the reliability information of the variable node is considered and the loop
update detection algorithm is introduced. The bit corresponding to the error code
word is flipped multiple times, before this is searched in the order of most
likely error probability to finally find the correct code word. Simulation
results show that the performance of one of the improved schemes is better than
the weighted symbol flipping (WSF) algorithm under different hexadecimal numbers
by about 2.2 dB and 2.35 dB at the bit error rate (BER) of 10-5 over an additive
white Gaussian noise (AWGN) channel, respectively. Furthermore, the average
number of decoding iterations is significantly reduced.
PMID- 29342962
TI - Functional Analyses of RUNX3 and CaMKIINalpha in Ovarian Cancer Cell Lines Reveal
Tumor-Suppressive Functions for CaMKIINalpha and Dichotomous Roles for RUNX3
Transcript Variants.
AB - (1) Background: Epithelial ovarian cancer (EOC) is the most lethal cancer of the
female reproductive system. In an earlier study, we identified multiple genes as
hypermethylated in tumors of patients with poor prognosis. The most promising
combination of markers to predict a patient's outcome was CaMKIINalpha and RUNX3.
Aim of this study was to functionally validate the importance of both genes. (2)
Methods: IC50 measurements, cell cycle distribution-, proliferation, and
migration experiments were conducted after transgene overexpression in two EOC
cell lines. (3) Results: We showed that CaMKIINalpha has tumor suppressive
functions in vitro and reduces proliferation, migration, and colony formation.
However, it had no effect on the reversion of the resistance to cisplatin. RUNX3
exhibited dualistic functions related to cisplatin sensitivity and migration
capacity, depending on the respective transcript variant (TV). A2780 cells
expressing RUNX3 TV2-the promoter of which harbors a CpG (5'-C-phosphate-G-3')
island and is potentially inactivated by hypermethylation-exhibited increased
cisplatin sensitivity and reduced migration properties. However, RUNX3 TV1, not
affected by CpG island methylation could be characterized as mediating resistance
and enhancing migration in A2780. The higher resistance of RUNX3 TV1 transfected
cells correlates with a reduction of cell proliferation. Moreover, RUNX3 TV1
expressing cells exhibit a reduced cell cycle arrest at the gap-2 or mitosis
phase (G2/M) under cisplatin treatment comparable to resistant A2780 subcultures.
(4) Conclusion: It appears that CaMKIINalpha and RUNX3 TV2 can reduce the
malignant potential of EOC cells.
PMID- 29342964
TI - Data-Driven Modeling and Rendering of Force Responses from Elastic Tool
Deformation.
AB - This article presents a new data-driven model design for rendering force
responses from elastic tool deformation. The new design incorporates a six
dimensional input describing the initial position of the contact, as well as the
state of the tool deformation. The input-output relationship of the model was
represented by a radial basis functions network, which was optimized based on
training data collected from real tool-surface contact. Since the input space of
the model is represented in the local coordinate system of a tool, the model is
independent of recording and rendering devices and can be easily deployed to an
existing simulator. The model also supports complex interactions, such as self
and multi-contact collisions. In order to assess the proposed data-driven model,
we built a custom data acquisition setup and developed a proof-of-concept
rendering simulator. The simulator was evaluated through numerical and
psychophysical experiments with four different real tools. The numerical
evaluation demonstrated the perceptual soundness of the proposed model, meanwhile
the user study revealed the force feedback of the proposed simulator to be
realistic.
PMID- 29342965
TI - Lipid-Based Nanoparticles as a Potential Delivery Approach in the Treatment of
Rheumatoid Arthritis.
AB - Rheumatoid arthritis (RA), a chronic and joint-related autoimmune disease,
results in immune dysfunction and destruction of joints and cartilages. Small
molecules and biological therapies have been applied in a wide variety of
inflammatory disorders, but their utility as a therapeutic agent is limited by
poor absorption, rapid metabolism, and serious side effects. To improve these
limitations, nanoparticles, which are capable of encapsulating and protecting
drugs from degradation before they reach the target site in vivo, may serve as
drug delivery systems. The present research proposes a platform for different
lipid nanoparticle approaches for RA therapy, taking advantage of the newly
emerging field of lipid nanoparticles to develop a targeted theranostic system
for application in the treatment of RA. This review aims to present the recent
major application of lipid nanoparticles that provide a biocompatible and
biodegradable delivery system to effectively improve RA targeting over free drugs
via the presentation of tissue-specific targeting of ligand-controlled drug
release by modulating nanoparticle composition.
PMID- 29342966
TI - Fabrication of a Textile-Based Wearable Blood Leakage Sensor Using Screen-Offset
Printing.
AB - We fabricate a wearable blood leakage sensor on a cotton textile by combining two
newly developed techniques. First, we employ a screen-offset printing technique
that avoids blurring, short circuiting between adjacent conductive patterns, and
electrode fracturing to form an interdigitated electrode structure for the sensor
on a textile. Furthermore, we develop a scheme to distinguish blood from other
substances by utilizing the specific dielectric dispersion of blood observed in
the sub-megahertz frequency range. The sensor can detect blood volumes as low as
15 MUL, which is significantly lower than those of commercially available
products (which can detect approximately 1 mL of blood) and comparable to a
recently reported value of approximately 10 MUL. In this study, we merge two
technologies to develop a more practical skin-friendly sensor that can be applied
for safe, stress-free blood leakage monitoring during hemodialysis.
PMID- 29342968
TI - A Fast and Robust Extrinsic Calibration for RGB-D Camera Networks.
AB - From object tracking to 3D reconstruction, RGB-Depth (RGB-D) camera networks play
an increasingly important role in many vision and graphics applications.
Practical applications often use sparsely-placed cameras to maximize visibility,
while using as few cameras as possible to minimize cost. In general, it is
challenging to calibrate sparse camera networks due to the lack of shared scene
features across different camera views. In this paper, we propose a novel
algorithm that can accurately and rapidly calibrate the geometric relationships
across an arbitrary number of RGB-D cameras on a network. Our work has a number
of novel features. First, to cope with the wide separation between different
cameras, we establish view correspondences by using a spherical calibration
object. We show that this approach outperforms other techniques based on planar
calibration objects. Second, instead of modeling camera extrinsic calibration
using rigid transformation, which is optimal only for pinhole cameras, we
systematically test different view transformation functions including rigid
transformation, polynomial transformation and manifold regression to determine
the most robust mapping that generalizes well to unseen data. Third, we
reformulate the celebrated bundle adjustment procedure to minimize the global 3D
reprojection error so as to fine-tune the initial estimates. Finally, our
scalable client-server architecture is computationally efficient: the calibration
of a five-camera system, including data capture, can be done in minutes using
only commodity PCs. Our proposed framework is compared with other state-of-the
arts systems using both quantitative measurements and visual alignment results of
the merged point clouds.
PMID- 29342969
TI - Feature Fusion of ICP-AES, UV-Vis and FT-MIR for Origin Traceability of Boletus
edulis Mushrooms in Combination with Chemometrics.
AB - Origin traceability is an important step to control the nutritional and
pharmacological quality of food products. Boletus edulis mushroom is a well-known
food resource in the world. Its nutritional and medicinal properties are
drastically varied depending on geographical origins. In this study, three sensor
systems (inductively coupled plasma atomic emission spectrophotometer (ICP-AES),
ultraviolet-visible (UV-Vis) and Fourier transform mid-infrared spectroscopy (FT
MIR)) were applied for the origin traceability of 192 mushroom samples (caps and
stipes) in combination with chemometrics. The difference between cap and stipe
was clearly illustrated based on a single sensor technique, respectively. Feature
variables from three instruments were used for origin traceability. Two
supervised classification methods, partial least square discriminant analysis
(FLS-DA) and grid search support vector machine (GS-SVM), were applied to develop
mathematical models. Two steps (internal cross-validation and external prediction
for unknown samples) were used to evaluate the performance of a classification
model. The result is satisfactory with high accuracies ranging from 90.625% to
100%. These models also have an excellent generalization ability with the optimal
parameters. Based on the combination of three sensory systems, our study provides
a multi-sensory and comprehensive origin traceability of B. edulis mushrooms.
PMID- 29342967
TI - Structural Diversity and Biological Activities of Cyclic Depsipeptides from
Fungi.
AB - Cyclic depsipeptides (CDPs) are cyclopeptides in which amide groups are replaced
by corresponding lactone bonds due to the presence of a hydroxylated carboxylic
acid in the peptide structure. These peptides sometimes display additional
chemical modifications, including unusual amino acid residues in their
structures. This review highlights the occurrence, structures and biological
activities of the fungal CDPs reported until October 2017. About 352 fungal CDPs
belonging to the groups of cyclic tri-, tetra-, penta-, hexa-, hepta-, octa-,
nona-, deca-, and tridecadepsipeptides have been isolated from fungi. These
metabolites are mainly reported from the genera Acremonium, Alternaria,
Aspergillus, Beauveria, Fusarium, Isaria, Metarhizium, Penicillium, and
Rosellina. They are known to exhibit various biological activities such as
cytotoxic, phytotoxic, antimicrobial, antiviral, anthelmintic, insecticidal,
antimalarial, antitumoral and enzyme-inhibitory activities. Some CDPs (i.e.,
PF1022A, enniatins and destruxins) have been applied as pharmaceuticals and
agrochemicals.
PMID- 29342971
TI - Walking Distance Estimation Using Walking Canes with Inertial Sensors.
AB - A walking distance estimation algorithm for cane users is proposed using an
inertial sensor unit attached to various positions on the cane. A standard
inertial navigation algorithm using an indirect Kalman filter was applied to
update the velocity and position of the cane during movement. For quadripod
canes, a standard zero-velocity measurement-updating method is proposed. For
standard canes, a velocity-updating method based on an inverted pendulum model is
proposed. The proposed algorithms were verified by three walking experiments with
two different types of canes and different positions of the sensor module.
PMID- 29342970
TI - The Possible Importance of beta3 Integrins for Leukemogenesis and Chemoresistance
in Acute Myeloid Leukemia.
AB - Acute myeloid leukemia (AML) is an aggressive bone marrow malignancy where the
immature leukemia cells communicate with neighboring cells through constitutive
cytokine release and through their cell surface adhesion molecules. The primary
AML cells express various integrins. These heterodimeric molecules containing an
alpha and a beta chain are cell surface molecules that bind extracellular matrix
molecules, cell surface molecules and soluble mediators. The beta3 integrin
(ITGB3) chain can form heterodimers only with the two alpha chains alphaIIb and
alphaV. These integrins are among the most promiscuous and bind to a large number
of ligands, including extracellular matrix molecules, cell surface molecules and
soluble mediators. Recent studies suggest that the two beta3 integrins are
important for leukemogenesis and chemosensitivity in human AML. Firstly, alphaIIb
and beta3 are both important for adhesion of AML cells to vitronectin and
fibronectin. Secondly, beta3 is important for the development of murine AML and
also for the homing and maintenance of the proliferation for xenografted primary
human AML cells, and for maintaining a stem cell transcriptional program. These
last effects seem to be mediated through Syk kinase. The beta3 expression seems
to be regulated by HomeboxA9 (HoxA9) and HoxA10, and the increased beta3
expression then activates spleen tyrosine kinase (Syk) and thereby contributes to
cytokine hypersensitivity and activation of beta2 integrins. Finally, high
integrin alphaV/beta3 expression is associated with an adverse prognosis in AML
and decreased sensitivity to the kinase inhibitor sorafenib; this integrin can
also be essential for osteopontin-induced sorafenib resistance in AML. In the
present article, we review the experimental and clinical evidence for a role of
beta3 integrins for leukemogenesis and chemosensitivity in AML.
PMID- 29342973
TI - Biogenic Weathering: Solubilization of Iron from Minerals by Epilithic Freshwater
Algae and Cyanobacteria.
AB - A sandstone outcrop exposed to freshwater seepage supports a diverse assemblage
of photosynthetic microbes. Dominant taxa are two cyanophytes (Oscillatoria sp.,
Rivularia sp.) and a unicellular green alga (Palmellococcus sp.). Less abundant
taxa include a filamentous green alga, Microspora, and the desmid Cosmarium.
Biologic activity is evidenced by measured levels of chlorophyll and lipids.
Bioassay methods confirm the ability of these microbes to dissolve and metabolize
Fe from ferruginous minerals. Chromatographic analysis reveals citric acid as the
likely chelating agent; this low molecular weight organic acid is detectable in
interstitial fluid in the sandstone, measured as 0.0756 mg/mL. Bioassays using a
model organism, Synechoccus elongates strain UTEX 650, show that Fe availability
varies among different ferruginous minerals. In decreasing order of Fe
availability: magnetite > limonite > biotite > siderite > hematite. Biotite was
selected for detailed study because it is the most abundant iron-bearing mineral
in the sandstone. SEM images support the microbiologic evidence, showing
weathering of biotite compared to relatively undamaged grains of other silicate
minerals.
PMID- 29342972
TI - The Effect of Combining Natural Terpenes and Antituberculous Agents against
Reference and Clinical Mycobacterium tuberculosis Strains.
AB - Background: On account of emergence of multi- and extensively drug-resistant
Mycobacterium tuberculosis (Mtb) strains, combinations of drugs with natural
compounds were tested to search for antibiotic activity enhancers. In this work
we studied terpenes (alpha-pinene, bisabolol, beta-elemene, (R)-limonene, (S)
limonene, myrcene, sabinene), which are the main constituents of essential oil
obtained from Mutellina purpurea L., a plant with described antitubercular
activity, to investigate their interactions with antibiotics against reference
Mtb strains and multidrug-resistant clinical isolates. Methods: The serial
dilution method was used to evaluate the minimal inhibitory concentration (MIC)
of tested compounds, while the fractional inhibitory concentration index (FICI)
was calculated for characterization of interactions. Moreover, IC50 values of
tested compounds were determined using monkey kidney epithelial cell line (GMK).
Results: The combinations of all studied terpenes with ethambutol or rifampicin
resulted in a synergistic interaction. Bisabolol and (R)-limonene decreased the
MIC for rifampicin at least two-fold for all tested strains, however no
synergistic action was observed against virulent strains. The tested terpenes
showed slight (bisabolol) or no cytotoxic effect against normal eukaryotic cells
in vitro. Conclusions: The obtained enhanced activity (FICI < 0.5) of ethambutol
and rifampicin against H37Ra strain under the influence of the studied terpenes
may be correlated to the capability of essential oil constituents to modify
bacterial resistance mechanisms in general. The observed differences in avirulent
and virulent bacteria susceptibility to terpenes tested separately and in
combinations with antibiotics can be correlated with the differences in the cell
wall structure between H37Ra mutant and all virulent strains.
PMID- 29342974
TI - Trypsin Binding with Copper Ions Scavenges Superoxide: Molecular Dynamics-Based
Mechanism Investigation.
AB - Trypsin is a serine protease, which has been proved to be a novel superoxide
scavenger. The burst of superoxide induced by polychlorinated biphenyls can be
impeded by trypsin in both wild type and sod knockout mutants of Escherichia
coli. The experimental results demonstrated that the activities of superoxide
scavenging of trypsin were significantly accelerated by Cu ions. Also, with the
addition of Cu ions, a new beta-sheet (beta7) transited from a random coil in the
Cu(II)-trypsin (TP) system, which was favorable for the formation of more
contacts with other sheets of trypsin. Residue-residue network analysis and the
porcupine plots proved that the Cu ion in trypsin strengthened some native
interactions among residues, which ultimately resulted in much greater stability
of the Cu(II)-TP system. Moreover, compact and stable trypsin structures with Cu
ions might be responsible for significantly provoking the activity of superoxide
scavenging.
PMID- 29342975
TI - Gallic Acid Alleviates Hypertriglyceridemia and Fat Accumulation via Modulating
Glycolysis and Lipolysis Pathways in Perirenal Adipose Tissues of Rats Fed a High
Fructose Diet.
AB - This study investigated the ameliorative effect of gallic acid (GA) on
hypertriglyceridemia and fat accumulation in perirenal adipose tissues of high
fructose diet (HFD)-induced diabetic rats. The previous results showed that
orally administered GA (30 mg/kg body weight) for four weeks significantly
reduced the levels of plasma glucose and triglyceride (TG) in HFD rats. GA also
markedly decreased the perirenal adipose tissues weight of HFD rats in present
study (p < 0.05). Western blot assay indicated that GA restored expression of
insulin signaling-related proteins, such as insulin receptor (IR), protein kinase
C-zeta (PKC-zeta), and glucose transporter-4 (GLUT4) in the perirenal adipose
tissues of HFD rats. Moreover, GA enhanced expression of glycolysis-related
proteins, such as phosphofructokinase (PFK) and pyruvate kinase (PK), and
increased the expression of lipolysis-related proteins, such as adipose
triglyceride lipase (ATGL), which is involved in lipolysis in the perirenal
adipose tissues of HFD rats. This study revealed that GA may alleviate
hypertriglyceridemia and fat accumulation through enhancing glycolysis and
lipolysis pathways in perirenal adipose tissues of HFD rats. These findings also
suggest the potential of GA in preventing the progression of diabetes mellitus
(DM) complications.
PMID- 29342976
TI - A Child's Concept of Pain: An International Survey of Pediatric Pain Experts.
AB - A child's 'concept of pain' refers to how they understand what pain actually is,
what function pain serves, and what biological processes are thought to underpin
it. We aimed to determine pediatric pain experts' opinions of: (1) the importance
and usefulness of assessing a child's concept of pain in clinical and/or research
settings; (2) the usefulness of the content of items within currently published
adult-targeted resources for assessing a child's concept of pain; and (3)
important domains of a child's concept of pain to assess. Forty-nine pediatric
pain experts (response rate = 75.4%) completed an online survey. Descriptive
statistics and frequency of responses were analyzed. Experts from all included
disciplines reported that assessing a child's concept of pain is important and
useful both clinically and in a research setting (>80% reported very or extremely
useful for each item). Experts considered that the content of 13 items from
currently published adult-targeted resources was useful, but the wording was too
complex for children aged 8-12 years. Experts considered that all seven of the
proposed domains of a child's concept of pain was important to assess. The
findings can be used to inform the development of an assessment tool for a
child's concept of pain.
PMID- 29342977
TI - Correction: Dierking, Ingo and Al-Zangana, Shakhawan. Lyotropic Liquid Crystal
Phases from Anisotropic Nanomaterials. Nanomaterials 2017, 7, 305.
AB - Due to an oversight during production, the authors wish to make the following
correction to reference [65] of this paper [...].
PMID- 29342979
TI - Catalysts on Formation of Carbon-Encapsulated Iron Nanoparticles from Kraft
Lignin.
AB - Effects of physical and chemical states of iron-based catalysts on the formation
of carbon-encapsulated iron nanoparticles (CEINs) synthesized thermally from
kraft lignin were investigated. Experimental results indicated that if solution
based iron nitrate (FeN) was used as an iron source for the catalyst, CEINs
observed were alpha-Fe and gamma-Fe-based cores encapsulated by few layers
graphitic-carbon (mostly 1-5 layers) and the majority of these CEINs were
embedded in amorphous carbon matrix. The formation of graphitic-carbon shells is
believed based on the dissolution and precipitation mechanism of amorphous carbon
acting as the carbon source. If solid-based iron nanoparticles (FePs) were used
as the catalyst, CEINs observed were alpha-Fe, gamma-Fe, and Fe3C-based cores
encapsulated with tangled graphitic-carbon nanoribbons and carbon tubules and the
majority of these CEINs were found along the edge of amorphous carbon matrix. The
growth of tangled graphitic-carbon nanoribbons and carbon tubules is based on a
chemical vapor decomposition process, i.e., the carbonaceous gases from kraft
lignin decomposition served as the carbon source.
PMID- 29342978
TI - Host-Guest Interaction of Cucurbit[8]uril with N-(3-Aminopropyl)cyclohexylamine:
Cyclohexyl Encapsulation Triggered Ternary Complex.
AB - The host-guest interaction of a series of cyclohexyl-appended guests with
cucurbit[8]uril (Q[8]) was studied by 1H NMR spectroscopy, isothermal titration
calorimetry (ITC), and X-ray crystallography. The X-ray structure revealed that
two cycloalkane moieties can be simultaneously encapsulated in the hydrophobic
cavity of the Q[8] host to form a ternary complex for the first time.
PMID- 29342980
TI - Dietary Intake of Flavonoids and Ventilatory Function in European Adults: A
GA2LEN Study.
AB - BACKGROUND: Flavonoids exert anti-inflammatory properties and modulate oxidative
stress in vitro, suggesting a protective effect on lung function, but
epidemiological studies examining this association are scarce. METHODS: A
stratified random sample was drawn from the GA2LEN screening survey, in which
55,000 adults aged 15 to 75 answered a questionnaire on respiratory symptoms.
Post-bronchodilator spirometry was obtained from 2850 subjects. Forced vital
capacity (FVC), the ratio between the forced exhaled volume in 1 second (FEV1)
and FVC (FEV1/FVC), FVC below lower limit of normal (FVC < LLN), and FEV1/FVC <
LLN were calculated. Intake of the six main subclasses of flavonoids was
estimated using the GA2LEN Food Frequency Questionnaire. Adjusted associations
between outcomes and each subclass of flavonoids were examined with multivariate
regressions. Simes' procedure was used to test for multiple comparisons. RESULTS:
A total of 2599 subjects had valid lung function and dietary data. A lower
prevalence of FVC < LLN (airway restriction) was observed in those with higher
total flavonoid (adjusted odds ratio (aOR), higher vs. lowest quintile intake
0.58; 95% Confidence Interval (CI) 0.36, 0.94), and pro-anthocyanidin intakes
(aOR 0.47; 95% CI 0.27, 0.81). A higher FEV1/FVC was associated with higher
intakes of total flavonoids and pro-anthocyanidins (adjusted correlation
coefficient (a beta-coeff 0.33; 0.10, 0.57 and a beta-coeff 0.44; 95% CI 0.19,
0.69, respectively). After Simes' procedure, the statistical significance of each
of these associations was attenuated but remained below 0.05, with the exception
of total flavonoids and airway restriction. CONCLUSIONS: This population-based
study in European adults provides cross-sectional evidence of a positive
association of total flavonoid intake and pro-anthocyanidins and ventilatory
function, and a negative association with spirometric restriction in European
adults.
PMID- 29342981
TI - Current Evidence on Vitamin D Deficiency and Metabolic Syndrome in Obese
Children: What Does the Evidence from Saudi Arabia Tell Us?
AB - Obesity and vitamin D deficiency represent major health problems among Saudi
children, and have been linked to chronic diseases. Obese children are at risk of
developing vitamin D deficiency, which appears to have negative influences on
energy homeostasis, impeded bone mineralisation, insulin resistance and
inflammation. Evidence supporting the association between vitamin D deficiency of
obese children and metabolic syndrome has not specifically been studied in early
childhood. The mechanisms through which vitamin D deficiency is associated with
metabolic syndrome in obese children needs further elucidation. This commentary
aims to (i) summarise current knowledge of the association between vitamin D
deficiency and metabolic syndrome in obese children; and (ii) discuss current
evidence for the association among Saudi Arabian children.
PMID- 29342982
TI - Detection of ZrO2 Nanoparticles in Lung Tissue Sections by Time-of-Flight
Secondary Ion Mass Spectrometry and Ion Beam Microscopy.
AB - The increasing use of nanoparticles (NP) in commercial products requires
elaborated techniques to detect NP in the tissue of exposed organisms. However,
due to the low amount of material, the detection and exact localization of NP
within tissue sections is demanding. In this respect, Time-of-Flight Secondary
Ion Mass Spectrometry (ToF-SIMS) and Ion Beam Microscopy (IBM) are promising
techniques, because they both offer sub-micron lateral resolutions along with
high sensitivities. Here, we compare the performance of the non-material
consumptive IBM and material-consumptive ToF-SIMS for the detection of ZrO2 NP
(primary size 9-10 nm) in rat lung tissue. Unfixed or methanol-fixed air-dried
cryo-sections were subjected to IBM using proton beam scanning or to three
dimensional ToF-SIMS (3D ToF-SIMS) using either oxygen or argon gas cluster ion
beams for complete sample sputtering. Some sample sites were analyzed first by
IBM and subsequently by 3D ToF-SIMS, to compare results from exactly the same
site. Both techniques revealed that ZrO2 NP particles occurred mostly
agglomerated in phagocytic cells with only small quantities being associated to
the lung epithelium, with Zr, S, and P colocalized within the same biological
structures. However, while IBM provided quantitative information on element
distribution, 3D ToF-SIMS delivered a higher lateral resolution and a lower limit
of detection under these conditions. We, therefore, conclude that 3D ToF-SIMS,
although not yet a quantitative technique, is a highly valuable tool for the
detection of NP in biological tissue.
PMID- 29342983
TI - Assessing the Perceptions and Practice of Self-Medication among Bangladeshi
Undergraduate Pharmacy Students.
AB - Objectives: To evaluate the perceptions and extent of practicing self-medication
among undergraduate pharmacy students. Methods: This cross-sectional,
questionnaire-based study was conducted over a six month period (January to June
2016) among undergraduate pharmacy students in five reputable public universities
of Bangladesh. It involved face-to-face interviews regarding self-medication of
250 respondents selected by simple random sampling. Results: Self-medication was
reported by 88.0% of students. Antipyretics (58.40%) were mostly preferred for
the treatment of fever and headaches. The major cause for self-medication was
minor illness (59.60%, p = 0.73) while previous prescriptions were the main
source of knowledge as well as the major factor (52.80%, p = 0.94) dominating the
self-medication practice. The results also demonstrated 88.80% of students had
previous knowledge on self-medication and 83.60% of students always checked the
information on the label; mainly the expiry date before use (85.60%). A
significant (p < 0.05) portion of the students (51% male and 43% female)
perceived it was an acceptable practice as they considered self-medication to be
a segment of self-care. Furthermore, students demonstrated differences in their
response level towards the adverse effect of drugs, the health hazard by a higher
dose of drug, a physician's help in case of side effects, taking medicine without
proper knowledge, and stopping selling medicine without prescription.
Conclusions: Self-medication was commonly used among pharmacy students primarily
for minor illnesses using over-the-counter medications. Although it is an
inevitable practice for them it should be considered an important public health
problem as this practice may increase the misuse or irrational use of medicines.
PMID- 29342984
TI - Amaranthus caudatus Stimulates Insulin Secretion in Goto-Kakizaki Rats, a Model
of Diabetes Mellitus Type 2.
AB - Diabetes Mellitus Type 2 prevalence is increasing worldwide; thus efforts to
develop novel therapeutic strategies are required. Amaranthus caudatus (AC) is a
pseudo-cereal with reported anti-diabetic effects that is usually consumed in
food preparations in Bolivia. This study evaluated the anti-diabetic
nutraceutical property of an AC hydroethanolic extract that contains mainly
sugars and traces of polyphenols and amino acids (as shown by nalysis with liquid
chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR)),
in type 2 diabetic Goto-Kakizaki (GK) rats and healthy Wistar (W) rats. A single
oral administration of AC extract (2000 mg/kg body weight) improved glucose
tolerance during Oral Glucose Tolerance Tests (OGTT) in both GK rats and in W
rats. Long-term treatment (21 days) with AC (1000 mg/kg b.w.) improved the
glucose tolerance evaluated by the area under the curve (AUC) of glucose levels
during the OGTT, in both GK and W rats. The HbA1c levels were reduced in both GK
(19.83%) and W rats (10.7%). This effect was secondary to an increase in serum
insulin levels in both GK and W rats and confirmed in pancreatic islets, isolated
from treated animals, where the chronic AC exposure increased the insulin
production 4.1-fold in GK and 3.7-fold in W rat islets. Furthermore, the effect
of AC on in vitro glucose-dependent insulin secretion (16.7 mM glucose) was
concentration-dependent up to 50 mg/mL, with 8.5-fold increase in GK and 5.7-fold
in W rat islets, and the insulin secretion in perifused GK and W rat islets
increased 31 and nine times, respectively. The mechanism of action of AC on
insulin secretion was shown to involve calcium, PKA and PKC activation, and G
protein coupled-exocytosis since the AC effect was reduced 38% by nifedipine (L
type channel inhibitor), 77% by H89 (PKA inhibitor), 79% by Calphostine-C (PKC
inhibitor) and 20% by pertussis toxin (G-protein suppressor).
PMID- 29342985
TI - Community-Based Health and Exposure Study around Urban Oil Developments in South
Los Angeles.
AB - Oilfield-adjacent communities often report symptoms such as headaches and/or
asthma. Yet, little data exists on health experiences and exposures in urban
environments with oil and gas development. In partnership with Promotoras de
Salud (community health workers), we gathered household surveys nearby two oil
production sites in Los Angeles. We tested the capacity of low-cost sensors for
localized exposure estimates. Bilingual surveys of 205 randomly sampled
residences were collected within two 1500 ft. buffer areas (West Adams and
University Park) surrounding oil development sites. We used a one-sample
proportion test, comparing overall rates from the California Health Interview
Survey (CHIS) of Service Planning Area 6 (SPA6) and Los Angeles County for
variables of interest such as asthma. Field calibrated low-cost sensors recorded
methane emissions. Physician diagnosed asthma rates were reported to be higher
within both buffers than in SPA6 or LA County. Asthma prevalence in West Adams
but not University Park was significantly higher than in Los Angeles County.
Respondents with diagnosed asthma reported rates of emergency room visits in the
previous 12 months similar to SPA6. 45% of respondents were unaware of oil
development; 63% of residents would not know how to contact local regulatory
authorities. Residents often seek information about their health and site-related
activities. Low-cost sensors may be useful in highlighting differences between
sites or recording larger emission events and can provide localized data
alongside resident-reported symptoms. Regulatory officials should help clarify
information to the community on methods for reporting health symptoms. Our
community-based participatory research (CBPR) partnership supports efforts to
answer community questions as residents seek a safety buffer between sensitive
land uses and active oil development.
PMID- 29342986
TI - Regioselectivity in Reactions between Bis(2-benzothiazolyl)ketone and Vinyl
Grignard Reagents: C- versus O-alkylation-Part III.
AB - The reaction between bis(2-benzothiazolyl)ketone and vinyl Grignard reagents
bearing different substituents on the vinyl moiety gave the product derived from
attack on the carbonylic carbon- and/or oxygen-atom. The regioselectivity of the
attack depends on the kind of substituents bound to the vinylic carbon atoms and
on their relative position. The reaction between vinylmagnesium bromide and 2
methyl-1-propenylmagnesium bromide was carried out under different experimental
conditions and in the presence of radical scavengers. The results indicate a
plausible mechanistic pathway involving radical intermediates in the case of O
alkylation, but a polar ones in the case of classic C-alkylation. This agrees
with our previous reports indicating a key role played by the delocalization
ability of the substituents bound to the carbonyl group in driving the
regioselectivity of the vinylmagnesium bromide attack towards O-alkylation.
Further support of this was obtained by diffractometric analysis of four distinct
bis(heteroaryl)ketones.
PMID- 29342987
TI - [Innovation is an inexhaustible driving force for the disciplinary development].
PMID- 29342988
TI - [Further improve the level of clinical study and management of pediatric
cardiovascular diseases in China].
PMID- 29342989
TI - [Expert consensus on the treatment of vasovagal syncope and postural tachycardia
syndrome in children].
PMID- 29342990
TI - [Intensive reading and interpretation of the expert consensus on the treatment of
vasovagal syncope and postural tachycardia syndrome in children].
PMID- 29342991
TI - [An analysis of clinical characteristics and acute treatment of supraventricular
tachycardia in children from a multicenter study].
AB - Objective: The study assessed the clinical characteristics and response to acute
intravenous antiarrhythmic drug therapy of supraventricular tachycardia (SVT) in
children. Methods: This was a multicenter prospective descriptive study including
257 children from First Hospital of Tsinghua University, Peking University First
Hospital, Children's Hospital Affiliated to Capital Institute of Pediatrics and
Beijing Anzhen Hospital who received intravenous antiarrhythmic drug therapy for
SVT from July 2014 to February 2017. The clinical and tachycardia features,
response to intravenous antiarrhythmic drug therapy of these children were
characterized. Statistical analyses were performed using t test, Mann-Whitney U
test, chi(2) test and H test. Results: The onset of SVT occurred at any age with
a distribution with positive skewness, 57.6% (n=148) children<1 year, 17.5%
(n=45) children1~<3 years, 10.5% (n=27) children 3~<6 years and 14.4% (n=37)
children >= 6 years of age. The percentages of SVT types were 49.4% (n=127) for
atrioventricular reentry tachycardia (AVRT), 4.3% (n=11) for atrioventricular
nodal reentry tachycardia (AVNRT), 26.8% (n=69) for unclassified paroxysmal SVT
and 19.5% (n=50) for atrial tachycardia (AT), respectively. Tachycardia-induced
cardionyopathy (TIC) secondary to SVT developed in 30 of 225 (13.3%). Left
ventricular ejection fraction (LVEF) of the 27 children attacked by TIC returned
to normal after successful control of SVT (41.1%+/-6.3% vs. 60.3%+/-9.2%, t=
10.397, P=0.000). Complete termination of SVT by antiarrhythmic drugs was
achieved in 164 of 257 (63.8%), partial termination rate was 18.7% (48 of 257)
and failure to terminate rate was 17.5% (45 of 257). Propafenone (complete
cardioversion in 98 (73.1%) of 134) and amiodarone (complete cardioversion in 23
(76.7%) of 30) showed better efficacy for SVT termination than adenosine
(complete cardioversion in 26 (44.1%) 59) (chi(2)=20.524, P=0.000). Paroxysmal
SVT had a higher termination rate on pharmacological therapy than AT (67.1% vs.
50.0%, chi(2)=6.337, P=0.042). Patients of different age groups had significantly
different response to antiarrhythmic therapy (chi(2)=13.904, P=0.031). Children<1
year of age showed the least response to antiarrhythmic drug therapy with
complete termination in 51 (55.4%) of 92. Adverse effects occurred in 9 patients
(3.5%): Four patients had severe hypotensive shock using propafenone (n=3) and
adenosine (n=1), and 3 patients had sinus arrest using adenosine. Conclusion:
Most (57.6%) children with SVT have their first clinical episode within 1 year of
age, and AVRT is the most common type. TIC occurs in 13.3% of children with SVT.
Intravenous antiarrhythmic drug therapy has a 63.8% complete termination rate for
children with SVT and incidence of adverse effects is 3.5%. Propafenone and
amiodarone are more effective for SVT termination in children than adenosine.
Serious adverse effects may occur when using propafenone.
PMID- 29342992
TI - [Radiofrequency catheter ablation of premature ventricular contractions in
children under CARTO3 system: a retrospective study from one single center].
AB - Objective: To evaluate the clinical effect and summarize the experience of
radiofrequency catheter ablation (RFCA) for children suffered from premature
ventricular contractions (PVCs). Methods: This retrospective study was conducted
by descriptive analysis. A total of 108 cases with frequent PVCs from Shanghai
Children's Medical Center were treated with RFCA under the guidance of CARTO3
system from January 2011 to December 2016. The immediate success rate of the
procedure, the recurrence rate and the perioperative complications were
summarized. The constituent ratio of different PVCs origins, the trend of overall
procedure time and success rate in recent years were analyzed. Statistical
analyses were performed using F test. Results: Immediate success of RFCA was
achieved in 104 cases (96.3%, 104/108) and 4 cases (3.7%, 4/108) failed. The PVCs
recurred during follow-up of over 6 months in 5 cases (4.8%, 5/104) . There were
no severe complications related to the procedure. The sites of PVCs origin, in 52
cases originated from right ventricular outflow track (48.2%, 52/108) , 17 cases
originated from left ventricular outflow track (15.7%, 17/108) and 26 cases
originated from tricuspid annulus (24.1%, 26/108) . Among the three predilection
sites of PVCs, the operation time was (141+/-46) min for right ventricular
outflow track, (155+/-50) min for left ventricular outflow track, and (166+/-57)
min for tricuspid annulus. However, the difference was not statistically
significant (F=1.79, P=0.17) . X-ray exposure time was (14+/-8) minutes for right
ventricular outflow track ablation, (32+/-14) minutes for left ventricular
outflow track ablation and (16+/-8) minutes for tricuspid annulus ablation
respectively. The exposure time for the ablation on left ventricle was
significantly longer than the other two sites (F=5.12, P=0.018) . Conclusion:
RFCA is safe and effective for PVCs in children with high success rate and low
recurrence and complication rates.
PMID- 29342993
TI - [Analysis of prognosis and associated risk factors in pediatric idiopathic
pulmonary arterial hypertension].
AB - Objective: To analyze the prognosis and associated risk factors of pediatric
idiopathic pulmonary arterial hypertension. Methods: A total of 119 patients
under 18 years of age diagnosed as idiopathic pulmonary arterial hypertension in
the Pulmonary Arterial Hypertension Center in Beijing Anzhen Hospital between
June 2007 and May 2017 were enrolled in this retrospective study. The clinical
informations and follow-up data were collected. The endpoints of follow-up were
defined as death or undergoing lung transplantation. Kaplan-Meier survival curve
was used to assess the survival,and the COX risk regression model was used to
analyze the prognostic risk factors. Results: The mean age at diagnosis was
(5.9+/-4.2) years. For 92 (77.5%) patients, the main reason for visit was
decreased activity with shortness of breath after exercise. Seventy patients
(58.8%) were in baseline NYHA functional class III-IV and 49 patients (41.2%)
were in NYHA functional class I-II. The mean systolic pulmonary arterial pressure
estimated by echocardiography was (90+/-23) mmHg (1 mmHg=0.133 kPa) . Right heart
catheterization was performed in 50 patients. Hemodynamic parameters revealed
that the mean pulmonary artery pressure was (66+/-19) mmHg. Mean right atrium
pressure was (8.5+/-3.4) mmHg. Mean pulmonary vascular resistance index was (17+/
9) wood.m(2) and the mean cardiac index was (3.4+/-1.3)L/m(2); 100 patients
(84.0%) received targeted therapy in which 55 patients (46.2%) were on
monotherapy,40 patients (33.6%) were on dual therapy and 5 patients (4.2%) were
on triple therapy. The mean time of follow-up was 22.0 months (0-108 months).
During follow-up, 43 patients (36.1%) died and 1 patient received double-lung
transplantation. Main causes of death including right heart failure, pulmonary
hypertension crisis, asphyxia and massive hemoptysis. The mean survival time from
diagnosis was 37.0 months,1-,2-,3-and 5-year survival rates were 86.3%, 72.2%,
51.4%and 37.8% respectively. Survival analysis showed that patients in baseline
NYHA functional class I-II had better prognosis. COX regression analysis showed
that NYHA function class, edema, increased total bilirubin and troponin
concentration and the pulmonary artery and aorta diameter ratio measured by
echocardiogram are risk factors of pediatric IPAH (HR=2.310, 2.723, 1.066, 1.696,
3.719, P=0.028, 0.005, 0.001, 0.024, 0.030) . While the existence of aterial
septal defect or patent foramen ovale, using bosentan and phosphodiesterase
inhibitors(,) dual or triple therapy were protective factors (HR=0.563, 0.559,
0.603, 0.682, 0.044, P=0.169, 0.076, 0.115, 0.258, 0.220) . In multivariate
analysis only edema associated with decreased survival (HR=2.398, P=0.025) .
Conclusion: Childhood idiopathic pulmonary arterial hypertension patients are
seriously ill at visit. Worse cardiac function classification at visit associate
with high mortality. Target therapy including using bosentan, dual or triple
therapy can improve survival.
PMID- 29342994
TI - [Report of antimicrobial resistance surveillance program in Chinese children in
2016].
AB - Objective: To analyze the antimicrobial resistance profile in Chinese children.
Methods: This was a prevalence survey. From January 1 through December 31, 2016,
the isolates were collected from 10 tertiary children hospitals in China.
Antimicrobial susceptibility testing was carried out by routine laboratory
methods. The penicillin susceptibility of streptococcus pneumonia and Meropenem
susceptibility of gram-negative bacteria were detected by E-test and disk
diffusion method respectively. Antimicrobial susceptibility results were
interpreted according to the criteria of Clinical and Laboratory Standards
Institute (CLSI) Guideline 2016. The data of antimicrobial susceptibility testing
of isolates from either the different patients (neonatal group and non-neonatal
group) or various sources were analyzed by WHONET 5.6 software. Results: A total
of 56 241 isolates were collected, of which 41.5% (23 328 isolates) were gram
positive organisms and 58.5% (32 886 isolates) gram-negative organisms. The five
leading pathogens were Escherichia coli (7 995/56 214, 14.2%), Straphylococcus
aureus (6 468/56 214, 11.5%), Streptococcus pneumonia (6 225/56 214, 11.1%),
Haemophilus influenza (5 435/56 214, 9.7%) and Klebsiella pneumonia (4 523/56
214, 8.0%). The Meropenem resistance rates of Klebsiella pneumonia, Enterobacter
cloacae, Escherichia coil, Pseudomonas aeruginosa, Acinetobacter baumonia
isolates were 27.4% (326/1 189) , 8.1% (29/358) , 2.0% (27/1 362) , 19.5%
(34/174) , 49.7% (230/463) in neonatal group and 15.4% (512/3 327) , 4.8%
(40/841) , 2.3% (151/6 564) , 13.7% (252/1 840) , and 53.4% (860/1 611) in non
neonatal group. The Methicillin-resistant Staphylococcus aureus (MRSA) rates of
neonatal group and non-neonatal group were 46.2% (649/1 404) and 33.3% (1 668/5
010) . The penicillin non-susceptible rates of Streptococcus pneumonia in the two
groups were 17.6% (6/34) and 18.2% (1 121/6 158) respectively. The beta-lactamase
positive rates of Haemophilus pneumonia isolates in the neonatal group and non
neonatal groups were 33.8% (47/139) and 44.4% (2 345/5 282) respectively.
Conclusion: This investigation highlights the worrisome trend of antimicrobial
resistance in children, especially among neonatal patients in China.
PMID- 29342995
TI - [Pediatric myeloid neoplasms associated with eosinophilia and platelet-derived
growth factor receptor beta gene rearrangement: a case report and literature
review].
AB - Objective: To investigate the clinical features and therapeutic strategies of
childhood myeloid neoplasms associated with eosinophilia and platelet-derived
growth factor receptor beta (PDGFRB) gene rearrangement. Methods: Clinical data
of myeloid neoplasms associated with eosinophilia and t (1;5) (q21;q33)
chromosomal translocation of PDGFRB gene rearrangement in a child hospitalized in
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical
Sciences on May 2015 was collected and analyzed. Using'eosinophilia
child'and'PDGFRB'as keywords, the relevant reports in literature were searched
from China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge
Service Platform, and Biomedical Literature Database (PubMed) until April 2017.
Results: The patient was a boy, 19 months old, who began to get sick at six
months after birth, with the main clinical manifestations of high fever,
diarrhea, epistaxis and hepatosplenomegaly. Peripheral blood smear showed a
significant elevation in white blood cells (127*10(9)/L) and
eosinophils(20.32*10(9)/L). Bone marrow examination showed hyperplastic marrow,
increased proportion of granulocytes, apparent visible eosinophils and decreased
megakaryocytes. Chromosome karyotype detection revealed t (1; 5) (q21; q33)
translocation. Fluorescence in situ hybridization (FISH) examination uncovered
that PDGFRB gene rearrangement was positive. The final diagnosis was myeloid
neoplasms with eosinophilia and PDGFRB gene rearrangement. After treatment with
oral imatinib 100 mg, once a day for 2 months, complete hematologic remission,
complete cytogenetic and molecular remission were all achieved. The relevant
literature was reviewed, no Chinese cases had been reported, 6 reports in English
literature have complete clinical data. Four cases had t (1; 5) translocation.
Four pediatric patients treated with imatinib achieved complete remission.
Conclusion: Myeloid neoplasms associated with eosinophilia and PDGFRB gene
rearrangement is extremely rare in children. Imatinib treatment can make these
patients quickly achieve complete hematologic remission, complete cytogenetic and
molecular remission. Imatinib should be recommended as the first line treatment
of these patients.
PMID- 29342996
TI - [Optimal energy supply in different age groups of critically ill children on
mechanical ventilation].
AB - Objective: To analyze the resting energy expenditure and optimal energy supply in
different age groups of critically ill children on mechanical ventilation in
pediatric intensive care unit (PICU). Methods: Patients on mechanical ventilation
hospitalized in PICU of Beijing Children's Hospital from March 2015 to March 2016
were enrolled prospectively. Resting energy expenditure of patients was
calculated by US Med Graphic company critical care management (CCM) energy
metabolism test system after mechanical ventilation. Patients were divided into
three groups:<3 years, 3-10 years, and >10 years. The relationship between the
measured and predictive resting energy expenditure was analyzed with correlation
analysis; while the metabolism status and the optimal energy supply in different
age groups were analyzed with chi square test and variance analysis. Results: A
total of 102 patients were enrolled, the measured resting energy expenditure all
correlated with predictive resting energy expenditure in different age groups (<3
years (r=0.3, P=0.0) ; 3~10 years (r=0.6, P=0.0) ;>10 years (r=0.5, P=0.0) ) . A
total of 40 cases in < 3 years group, including: 14 cases of low metabolism
(35%), 14 cases of normal metabolism (35%), and 12 cases of high metabolism
(30%); 45 cases in 3-10 years group, including: 22 cases of low metabolism (49%),
19 cases of normal metabolism (42%), 4 cases of high metabolism (9%); 17 cases
in>10 years group, including: 12 cases of low metabolism (71%), 4 cases of normal
metabolism (23%), 1 case of high metabolism (6%). Metabolism status showed
significant differences between different age groups (chi(2)=11.30, P<0.01, r=
0.01). Infants had higher metabolic status, which lessened with aging. The total
average actual energy requirement was (210+/-84) kJ/ (kg?d) . There were
significant differences in actual energy requirement between age groups (F=46.57,
P<0.001), with (277+/-77) kJ/ (kg?d) in<3 years group, (184+/-53) kJ/ (kg?d) in 3
10 years group, and (120+/-30) kJ/ (kg?d) in>10 years group. Conclusion: The
resting energy metabolism of the critically ill children on mechanical
ventilation is negatively related to the age. The actual energy requirement
should be calculated according to different ages.
PMID- 29342997
TI - [X-linked inhibitor of apoptosis deficiency manifested as Crohn's disease: a case
report and literature review].
AB - Objective: To analyze the clinical characteristics of X-linked inhibitor of
apoptosis (XIAP) deficient patients with clinical manifestation of Crohn's
disease. Methods: Clinical manifestations, laboratory investigations, genetic
testing and therapeutic interventions of one case of XIAP deficiency who was
admitted to Department of Gastroenterology in Children's Hospital, Zhejiang
University School of Medicine in May 2016 were summarized. PubMed and Chinese
database for articles published from January 2016 to June 2017 were searched
using the key words of'Crohn's disease'and'XIAP', and the relevant literature was
reviewed. Results: The case we reported was a 6-year-1-month-old boy with
recurrent bloody stool for 2 months, and abdominal pain with fever for 2 weeks.
The patient had a past history of hemophagocytic lymphohistiocytosis (HLH) and
epilepsy in the past one year. Complete blood cell count showed mild anemia
(Hb108 g/L). The patient had an elevated high-sensitivity C reactive protein (86
mg/L) and erythrocyte sedimentation rate (46 mm/1h) . White blood cells, pus
cells and red blood cells were found on routine stool examination. Biochemical
panel showed hypoalbuminemia (25.2 g/L) , elevated transaminase (alanine
aminotransferase 175 U/L, aspartate transaminase 229 U/L) , hypertriglyceridemia
(4.41 mmol/L) , and hyperferritinemia (>1 650.0 MUg/L) . Magnetic resonance
enterography revealed the intestinal wall thickening and increased enhancement in
parts of illeum and colon. Capsule endoscopy revealed multiple ulcers in jejunum.
Colonoscopy showed multiple ulcers in colon and the pathological examination
revealed chronic inflammation in mucosa of terminal ileum and colon, which was
combined with partial necrosis and ulceration. Some phagocytes were seen in bone
marrow smears. The patient was given multiple diagnoses, including hemophagocytic
lymphohistiocytosis, Crohn's disease, sepsis, epilepsy, severe malnutrition, and
hypoproteinemia. The pediatric Crohn's disease activity index (PCDAI) was 37.5.
Genetic testing identified a hemizygotic mutation of c.910G>T chrX:123022501
p.G304X in XIAP. The parents had no such mutation. The patient showed response to
infliximab with oral intake of mercaptopurine and corticosteroids, and had
remission with PCDAI of 0. There were 9 relevant articles (Chinese 0 English 9),
which showed 33.3% XIAP deficient patients manifested with inflammatory bowel
disease(IBD), who might have other manifestations such as hemophagocytic
lymphohistiocytosis or splenomegaly simultaneously or sequentially. Those
patients showed poor response to monotherapy. Conclusion: XIAP deficient patients
have various clinical manifestations. Genetic testing is important to those male
pediatric IBD patients who have the complicated symptoms or little response to
standard therapy.
PMID- 29342998
TI - [X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection,
and neoplasia: report of a family and literature review].
AB - Objective: To investigate the clinical features and genetic characteristics of
cases with X-linked immunodeficiency with magnesium defect, Epstein-Barr virus
(EBV) infection, and neoplasia (XMEN). Methods: Characteristics of clinical
material, immunological data and gene mutation of two cases with XMEN in the same
family in China were retrospectively analyzed. The related reports literature
were searched by using search terms'MAGT1 gene'or'XMEN'. Results: The proband, a
2-year-eight-month old boy, was admitted due to 'Urine with deepened color for
two days and yellow stained skin for one day'. He had suffered from recurrent
upper respiratory tract infection and sinusitis previously. Hemoglobin level was
38 g/L. The absolute count of reticulocytes was 223.2*10(9)/L. Urobilinogen level
was 38 MUmol/L (3-16 MUmol/L). Coomb's test was positive. Both total (77.2
MUmol/L) and indirect bilirubin (66 MUmol/L) levels were elevated. There was an
inverted CD4(+)/CD8(+)T cell ratio (0.89). The gene sequencing results showed
MAGT1 gene c.472delG, p.D158Mfs*6 mutation. His 1-year-6-month old brother, was
also identified to have MAGT1 gene c.472delG, p.D158Mfs*6 mutation.The younger
brother mainly suffered from recurrent upper respiratory tract infection,
accompanied by an inverted CD4(+)/CD8(+)T cell ratio (0.45), an elevated ratio
and number of total B cells (45.7%). A total of 7 reports were retrieved
including 11 male cases caused by MAGT1 gene mutation. These 11 cases were
characterized by EBV viremia (11 cases), recurrent upper respiratory tract
infection, otitis media or sinusitis (10 cases), secondary neoplasia diseases (8
cases), reduction of CD4(+)/CD8(+) T cell ratio (7 cases),and autoimmune
thrombocytopenia or hemolytic anemia (2 cases). Conclusion: XMEN often manifests
as male onset, recurrent upper respiratory tract infection, otitis media or
sinusitis, EBV viremia, lymphoproliferative disease or lymphoma, autoimmune
diseases and reduction of CD4(+)/CD8 (+)T cell ratio. NKG2D expression in NK
cells is significantly reduced, and gene sequencing analysis shows a pathogenic
mutation in MAGT1 gene.
PMID- 29343000
TI - [X-linked hyper-IgM syndrome complicated interstitial lung disease induced by
virus in two pediatric cases].
PMID- 29343001
TI - [Pulmonary mucoepidermoid carcinoma in a child].
PMID- 29342999
TI - [Risk factors analysis and prognosis of renal pelvis dilatation in high-risk
infants in monocenter].
AB - Objective: To explore the prognosis and risk factors of pyelectasis in high-risk
infants. Methods: This was a retrospective study. Totally 960 high-risk infants,
who accepted type B ultrasonic examination for fetus at 28th week of gestation
and for newborns in 48 hours after birth, were included in the study in
departments of obstetrics and eonatology, Shunyi Maternal and Children's Hospital
of Beijing Children's Hospital during May 2012 to April 2013. The degree of
pyelectasis was classified using Grignon grade and the paients were followed up
for 3 years. The factors of epidemiology, high risk pregnant women, fetus and
high-risk newborns that relate to pyelectasis were summarized. High-risk factors
were analyzed by using logistic multivariate regression analysis. Results: Of 960
high-risk infants, 103 had abnormal urinary ultrasound results, 87 (9.1% of high
risk infants) were diagnosed with pyelectasis, 16 (1.7% of high-risk infants)
were diagnosed with congenital anomalies of the kidney and urinary tract.
According to the degree of pyelectasis, 68 infants were Grignon grade I,
male:female ratio=5.8?1, left side:right side ratio=1.91?1; 19 infants were
Grignon grade II, male:female ratio=5.33?1, left side:right side ratio=2.12?1.
Postnatal follow-up results showed that pyelectasis disappeared in 48 cases (55%
of pyelectasis cae), 40 infants were Grignon grade I (59% of all Grignon grade I
patients), 8 infants were Grignon grade II (42% of all Grignon grade II
patients); The result of risk factors analysis showed that the risk of
pyelectasis in males was 4.368 times that of females (95%CI: 2.33-8.189, P<0.05);
the risk of pyelectasis in low birth weight infants was 22.434 times that of non
low birth weight infants (95% CI: 5.883-85.547, P<0.05). Conclusion: The
incidence of pyelectasis in high-risk infants was 9.1%. The mitigation rate of
pyelectasis in Grignon grade I to II in fetal or newborn period is high. Patients
in Grignon grade III and above in fetal or new born period had high risk of
congenital anomalies of the kidney and urinary tract. The risk of pyelectasis of
male was higher than that of female; the risk of pyelectasis of low birth weight
infant was higher than appropriate for gestational age infants.
PMID- 29343002
TI - [A case of abdominal Castleman disease].
PMID- 29343003
TI - [Schuurs-Hoeijmakers syndrome in a child].
PMID- 29343004
TI - [Fanconi-Bickel syndrome with SLC2A2 gene mutation in a child].
PMID- 29343005
TI - [Role of long noncoding RNA in chronic hepatitis B infection].
PMID- 29343006
TI - [Epidemiology of heart arrest in children].
PMID- 29343008
TI - [Effects of obstructive sleep apnea syndrome on vascular endothelial function in
and mechanisms children].
PMID- 29343007
TI - [Introduction to the 6th National Conference of Pediatric Syncope].
PMID- 29343009
TI - [The thinking and challenge from the drug-resistant tuberculosis guidelines by
World Health Organization].
PMID- 29343010
TI - [Diagnosis and treatment of extrapulmonary non-tuberculous mycobacterial
diseases].
PMID- 29343011
TI - [Molecular genetic mechanism of anti-tuberculous drug induced liver injury].
PMID- 29343012
TI - [The effectiveness of individualized treatment regimen on smear-positive
retreatment pulmonary tuberculosis with mono- and poly-drug resistance].
AB - Objective: To analyze and evaluate the effectiveness of individualized treatment
regimen in the therapy of smear-positive retreatment pulmonary tuberculosis with
mono-and poly-drug resistance, and therefor to provide information on how to
develop rational individualized regimen for retreatment tuberculosis cases with
drug resistance. Methods: This was a multi-centered, prospective cohort study.
Totally 254 cases of sputum positive tuberculosis with previous treatment history
during the period from July 1, 2009 to August 30, 2016 were included in the
analysis. All the cases were randomly divided into 3 groups and received therapy
after randomization into treatment groups. After 3 months, cases with multidrug
resistant tuberculosis, extensively drug-resistant tuberculosis, non-tuberculosis
mycobacterial infection and those with smear-positive but culture-negative
tuberculosis were excluded according to result of sputum culture and drug
susceptibility test (DST). In treatment group A (individualized treatment group),
86 cases with an average age of (42.1+/-13.7) years for men and (38.5+/-12.8)
years for women, were treated with individualized regimen, which allowed drug
replacement on the basis of standard regimen (2SHRZE/6HRE) according to DST
result. Treatment duration was recalculated after drug replacement and the total
length should be 12 months or more. If the DST result did not show drug
resistance, the patients would continue the 8 months' standard treatment. In
treatment group B (intensified retreatment regimen group), 86 cases with an
average age of (43.2+/-14.2) years for man and (37.9+/-14.1) years for women,
received intensified retreatment regimen (2HL(2)EZS/2HL(2)EZS(3)/4HL(2)E). The
dose for H was 0.3 g/d for patients with body weight <50 kg, and 0.4~0.5 g/d for
higher body weight (>=50 kg); The doses for L(2,)E and Z were 0.6 g, 2/w; 0.75,
1/d and 0.5g, 3/d. In treatment group C (standard treatment group), 82 cases with
an average of (42.5+/-11.9) years for man and (38.6+/-12.8) years for women, were
treated with standardized regimen recommended by national tuberculosis program
(2HREZS/6HRE). In both group B and C, the total treatment duration was 8 months
and the drugs were not replaced for mono-and poly-drug resistance. Treatment
outcomes of the 3 groups were analyzed, the status of drug replacement in group A
was analyzed, and the adjustment of dose of H and R according to patients' body
weight was observed. SPSS 19.0 was used for data analysis. Results: The treatment
cure rates for group A, B and C were 73.3%(63/86), 76.7%(66/86) and 50%(41/82),
and the treatment success rates were 80.2%(69/86), 84.9%(73/86) and 62.2%(51/82)
respectively. Treatment failure was 8.1%(7/86), 4.7%(4/86) and 19.5%(16/82) in 3
groups. There were significant differences in the above indicators for group A
and B in comparison with group C(chi(2)=13.127, P=0.001). However, there was no
difference observed between group A and B(chi(2)=0.646, P=0.422). In group A,
tuberculosis specialized hospitals using regular doses for R was only
38.7%(12/31). After 3 years' follow-up, no-relapse-success for group A was 66.7%
(10/15). Conclusions: Inappropriate individualized treatment would increase
treatment failure for retreatment tuberculosis. Higher doses of H and R and
prolonged extensive therapy phase could contribute to increased treatment
success.
PMID- 29343013
TI - [The plasma level and gene expression in peripheral blood of interleukin-35 in
patients with sarcoidosis and its clinical significance].
AB - Objective: To investigate the expression of interleukin(IL)-35 protein and gene
in peripheral blood of patients with sarcoidosis and its clinical significance.
Methods: Peripheral blood samples from 98 patients with sarcoidosis and 98
healthy volunteers were collected at Peking Union Medical College Hospital
between January 2016 and March 2017. The plasma levels of IL-35 were detected by
enzyme-linked immunosorbent assays (ELISA), and the relationship between IL-35
and the clinical characteristics was analyzed. Real-time quantitative PCR was
used to detect the expression levels of IL-35 subunit EBI3, p35 and T regulatory
cell transcription factor Foxp3 mRNA in peripheral blood mononuclear cells, and
their correlations were analyzed. Results: The plasma levels of IL-35 in patients
with sarcoidosis (44+/-12) ng/L was significantly lower than that in the normal
control group (55+/-12) ng/L (P<0.001). There was a positive correlation between
the plasma levels of IL-35 and D(L)CO% predicted values (r=0.76, P<0.001), but it
showed no significantly correlation with other clinical parameters. The
expression of EBI3 and Foxp3 mRNA in peripheral blood mononuclear cells of
patients with sarcoidosis (1.54+/-0.74, 0.92+/-0.36) were significantly lower
than those in the normal control group respectively (2.12+/-0.61, 1.10+/-0.27,
all P<0.05). There was a significant positive correlation between the expression
of EBI3 and Foxp3 mRNA in the sarcoidosis group (r=0.786, P<0.001). Conclusion:
IL-35 may be involved in the inflammatory process of sarcoidosis and play an
important role in the pathogenesis of the disease.
PMID- 29343014
TI - [Correlation between peripheral venous oxygen saturation and hemodynamic
parameters in patients with pulmonary hypertension].
AB - Objective: To investigate the correlation of peripheral venous oxygen saturation
(SpvO(2)) with mixed venous oxygen saturation (SvO(2)), pulmonary vascular
resistance (PVR) and cardiac index (CI) in patients with pulmonary hypertension
(PH), in order to predict these parameters using SpvO(2) and assess the prognosis
of patients. Methods: Hospitalized patients diagnosed with PH by right heart
catheterization in the Guangzhou Institute of Respiratory Diseases from July 2015
to October 2016 were retrospectively analyzed. Parameters during the right heart
catheterization, including SvO(2,)SpvO(2,)cardiac output (CO) and mean pulmonary
arterial pressure (mPAP) were recorded, while CI, PVR and other parameters were
indirectly calculated. The correlation between SpvO(2) and SvO(2,)CO, CI, mPAP,
PVR and other parameters were respectively analyzed and compared between groups.
Results: A total of 77 PH patients were selected, which comprised of 39 males and
38 females. The results revealed that SpvO(2) was correlated positively with
SvO(2,)CI and PaO(2) (P<0.05), but negatively with PVR, total pulmonary
resistance (TPR), systemic vascular resistance, right atrial diameter and right
ventricular diameter (P<0.05). In the group with SpvO(2) <65%, the dilation of
the right atrium and right ventricle was more significant, the WHO heart function
grade was worse, CI, systemic systolic pressure and mean systemic pressure were
lower, and PVR and TPR were higher, as compared to those in the group with
SpvO(2) >=65%. (P<0.05). Conclusions: There was good consistency between SpvO(2)
and SvO(2). Furthermore, SpvO(2) could indirectly reflect the CI, PVR and changes
in right heart structure of PH patients, providing reference for the clinical
prediction of CI and PVR, as well as the prognosis of PH patients, through the
use of SpvO(2). Low SpvO(2) indicated a severe condition and poor prognosis.
PMID- 29343015
TI - [Clinical and imaging features of pulmonary veno-occlusive disease and pulmonary
capillary hemangioma].
AB - Objective: To improve the diagnosis and treatment of the pulmonary veno-occlusive
disease (PVOD) and pulmonary capillary hemangioma (PCH). Methods: The clinical
features, radiological findings, laboratory testing and treatment in 8 cases of
PVOD/PCH which was diagnosed from 2013 to 2017 were described. Results: PVOD/PCH
was rare. The clinical symptoms were easily confused with IPAH, but the decrease
of hypoxemia, clubbing, D(L)CO were more obvious, and the imaging features of
HRCT were helpful for PVOD/PCH diagnosis. Combined with gene testing, it was
helpful to diagnose PVOD/PCH and avoid the risk of surgical biopsy. Conclusion:
PVOD and PCH are rare type of pulmonary vascular diseases. According to clinical
manifestations, physical examination, pulmonary function test results, HRCT
imaging, CPET and gene detection results, PVOD or PCH can be diagnosed.
PMID- 29343017
TI - [Review of meropenem-clavulanate combination in the treatment of multidrug
resistant and extensively durg-resistant tuberculosis].
PMID- 29343016
TI - [Effectiveness and safety in bronchoscopy under anesthesia with fentanyl combined
with midazolam].
AB - Objective: To study the effectiveness and safety in bronchoscopy under anesthesia
with fentanyl combined with midazolam. Methods: We randomly allocated 132
patients( male 69, female 63, median age 62.9 years)requiring bronchoscopy in
Beijing Xuanwu Hospital into 2 groups during January 2015 to December 2016.The
trial group included 66 patients, receiving fentanyl combined with midazolam for
anesthesia, while the control group of 66 patients receiving 2% lidocaine for
topical anesthesia.In the trial group, there were 37 males and 29 females, with a
median age of 63 years (range 26-82). In the control group, there were 36 males
and 30 females, with a median age of 62.8 years (range 30-82). The pulse, mean
arterial pressure, and the oxygen saturation of the patients were recorded before
anesthesia and 5 minutes after deep anesthesia was reached. Changes of vital
signs and adverse reactions during the bronchoscopy were also observed. Results:
The fluctuation of pulse(12.3+/-2.3)/min, mean arterial pressure(5.9+/-2.2)mmHg(1
mmHg=0.133 kPa) and oxygen saturation(4.4+/-1.3)%was lower in the trial group as
compared to that of the control group, pulse(21.9+/-1.8)/min, mean arterial
pressure(7.1+/-2.3)mmHg, oxygen saturation(13.3+/-4.2)%, P<0.001.Five minutes
after anesthesia, the pulse(80.0+/-11.9)/min, the mean arterial pressure(95.0+/
9.7)mmHg and the oxygen saturation(90.0+/-5.67)%of patients in the trial group
were lower than those in the control group [pulse(90.3+/-17.0)/min, mean arterial
pressure(102.7+/-12.4)mmHg, oxygen saturation(96.5+/-3.0)%], the differences
being statistically significant(P<0.001). The trial group also showed smaller
fluctuation, better tolerance, and fewer adverse reaction sthan the control
group. Conclusion: Fentanyl combined with midazolam is safe and effective in
bronchoscopy with fewer adverse reactions, but its early effect on the vital
signs should be monitored and stricter indications may be needed.
PMID- 29343018
TI - [Research progress of exosomes in lung diseases].
PMID- 29343019
TI - [Advances in preoperative screening of obstructive sleep apnea hypopnea
syndrome].
PMID- 29343020
TI - [The application of noninvasive positive pressure ventilation to a pulmonary
rehabilitation program in patients with chronic obstructive pulmonary Disease].
PMID- 29343021
TI - [The role of aquaporin in the development of pulmonary diseases].
PMID- 29343022
TI - [Inheriting the excellence to innovate medical research in China].
PMID- 29343023
TI - [Emphasis on perioperative and long-term treatment is the key to improve the
prognosis of patients with craniopharyngiom].
PMID- 29343024
TI - [Hypopituitarism mode in patients with craniopharyngioma in relation to tumor
growth pattern].
AB - Objective: To investigate the pituitary hormone changes of patients with
craniopharyngioma of different growth patterns during perioperative period and
follow up time. Methods: Retrospective studies were performed on 212 cases of
primary craniopharyngioma patient who received total tumor excision surgery in
our hospital from January 2001 to May 2012. The characteristics of pituitary
hormone and associated clinical manifestation during preoperative, perioperative
and postoperative periods were analyzed according to the QST surgical
classification. Results: One hundred and seventy-seven (83.5%) of patients
present preoperative hypopituitarism, 36 of them were panhypopituitarism. The
hypopituitarism condition was exacerbated during the early stage of post
operation period. The abnormal rates of HPA and HPT during the follow up were
60.1% and 58.3% respectively and hormone replacement treatment was needed for
these patients. Craniopharyngioma of different growth patterns showed diversities
in the characteristics of hypopituitarism. Conclusion: QST surgical
classification was closely associated with the pattern of hypopituitarism, it can
help to optimize treatment and prognosis estimation, and could be important
criterion for improving the clinical practice of neuroendocrine monitoring,
treatment and health education of patients with craniopharyngioma.
PMID- 29343025
TI - [Correlation between the parameters of acoustic cardiography and BNP, LVEF and
cardiac function grading in patients with chronic heart failure].
AB - Objective: To explore the correlation between the parameters of the new
generation of Acoustic Cardiography and brain natriuretic peptide (BNP), left
ventricular ejection fraction (LVEF) and cardiac function grading in the
diagnosis of heart failure. Methods: One hundred and sixty-eight inpatients, who
were hospitalized in Department of Cardiology, Haikou People's Hospital from May
2016 to July 2017, were enrolled as heart failure group, including NYHA class
I(n=29), NYHA class II(n=40), NYHA class III(n=64), NYHA class IV (n=35). And
eighty-seven patients with normal cardiac function were selected as healthy
control group. The data of the two groups were analyzed after the Acoustic
Cardiography test, BNP determination and LVEF examination. Results: The
differences in QRS duration, electromechanical activation time (EMAT), EMAT%,
systolic dysfunction index (SDI), third heart sound (S3) and other indicators
among the groups with different levels of cardiac function were statistically
significant (P<0.05). The difference in left ventricular systolic time (LVST)
between the cardiac function grade I and healthy group was not significant
(P>0.05), while the differences among the rest groups were significant. There was
a positive correlation between QRS duration, EMAT%, SDI, S3 and BNP (t=9.46,
11.38, 12.14, 9.67, respectively, P<0.05); LVST and BNP were negatively
correlated (t=-14.27, P<0.05). There was a negative correlation between QRS
duration, EMAT%, SDI, S3 and LVEF (t=11.24, -8.764, -2.393, -0.579, respectively,
P<0.05). There was a positive correlation between LVST and LVEF (t=23.48,
P<0.05). There was a positive correlation between QRS duration, EMAT%, SDI, S3
and cardiac function grading (beta=0.003, 0.234, 0.419, 0.352, respectively,
P<0.05). There was a negative correlation between LVST and cardiac function grade
(beta=-0.021, P<0.05). Conclusion: The parameters of the Acoustic Cardiography
test (EMAT%, EMAT, SDI, S3 ) are closely related to BNP, LVEF and cardiac
function grading, and can be used as assistant indexes for the diagnosis and
evaluation of heart failure.
PMID- 29343026
TI - [Applied research of "quadri-low" combined with automatic tube current modulation
and iterative model reconstruction technology in head and neck CT angiography].
AB - Objective: To investigate the feasibility of low tube voltage, low contrast
medium concentration, injection rate and volume (quadri-low) combined with
automatic tube current modulation (ATCM) and iterative model reconstruction (IMR)
technology in head and neck CT angiography (CTA). Methods: A total of 70 patients
whose body mass index (BMI)<25 kg/m(2) underwent head and neck CTA and digital
subtraction angiography (DSA) from January to July 2017 were enrolled in this
prospective study. According to random number table, patients were divided into
two groups: group A (n=35) was scanned according to the protocol of 120 kV, 150
mAs, 50 ml and 5 ml/s iopromide (370 mg/ml) and filtered back projection (FBP)
reconstruction; group B (n=35) was scanned with 80 kV, ATCM with mean tube
current of 100 mAs, 30 ml and 3 ml/s iohexol (300 mg/ml) and IMR; the other
parameters kept consistent between the two groups. The maximum transverse neck
diameter at the level of the hyoid bone, artery CT value and image noise were
measured, signal to noise ratio (SNR), contrast to noise ratio (CNR) and figure
of merit (FOM) were calculated, and the image quality was evaluated subjectively
and compared with those reconstructed by DSA. Scan length, volume CT dose index
(CTDIvol) and dose length product (DLP) were recorded, and the effective dose
(ED) was calculated. The chi-square and independent-sample t tests were used to
compare the inter-group differences in these aforementioned data. Resutls: No
significant difference was found in general information between the two groups.
No significant difference existed in artery CT value, image noise, SNR and CNR
between the two groups (t=-1.170-1.365, all P>0.05); however, the FOM of group B
(74+/-40) was significantly higher than that in group A (12+/-4) (Z=-7.195,
P=0.000). The image quality of the two groups met the requirement of clinical
diagnosis[(4.1+/-0.7) vs (4.2+/-0.8) points, Z=-0.592, P>0.05], no significant
difference was found in subjective evaluation and diagnostic efficacy. The
CTDIvol, DLP and ED in group B were all significantly lower than those in group A
(Z=-7.728, -7.202, -7.206, all P<0.05). The iodine load and iodine delivery rate
(IDR) of group B was lower than that of group A (18.5 g vs 9.0 g, 1.85 mg/s vs
0.90 mg/s), and they were reduced for 51.4% in group B. Conclusions: For patients
of BMI <25 kg/m(2,) low tube voltage, low contrast medium concentration,
injection rate and volume combined with ATCM and IMR technology can significantly
decrease radiation dose, iodine load and IDR while maintain the image quality in
head and neck CTA examination.
PMID- 29343027
TI - [Using creatinine reduction ratio as a predictor for delayed graft function of
kindey transplant recipients from donor of cardiac death].
AB - Objective: To explore the relationship between creatinine reduction ratio (CRR)
and delayed graft function among kidney transplant recipients from donor of
cardiac death (DCD). To define the value of CRR to predict delayed graft function
(DGF) in early post-transplant period. Method: 86 patients were included, who
received renal transplantation from DCD during Jan 1(st) 2011 to Jun 30(th) 2016.
We performed a retrospective study and collected creatinine data within 3 days
post-operation and marked them with Cr1, Cr2 , Cr3, and then calculated
creatinine reduction ratio day-2 (CRR 2) =(Cr1-Cr2)/Cr1*100% and creatinine
reduction ratio day-3 (CRR 3)=[(Cr1-Cr2)/Cr1+ (Cr2-Cr3)/Cr2]/2*100%. Patients
were divided into two groups by DGF or not. We compared the CRR differenc between
DGF group and no DGF group, and drew the receiver operating characteristic curve
(ROC curve) to find out the cut-off value to predict delayed graft function.
Results: Among 86 patients, DGF appeared in 17 patients. The incidence of DGF was
19.8%. The CRR 2 of patients in no DGF group was (37.5+/-17.4)% while patients in
DGF group was (2.0+/-24.8)% (P<0.001). The CRR 3 of patients in no DGF group was
(32.5+/-13.1)%, while patients in DGF group was (6.8+/-17.1)% (P<0.001).
Acorrding to ROC curve, when cut-off value of CRR 2 was defined as <20.7%, the
predicted value of DGF was the best, sensitivity was 85.5%, specificity was
76.5%, and area under the curve was 0.876. In the same way, when CRR 3 was
defined as <17.6%, sensitivity was 89.9%, specificity was 76.5%, area under the
curve was 0.872. Conclusion: It is reliable to predict DGF by CRR during early
post-operative period. CRR shows high sensitivity and specificity and it is
simple. It could guide the adjustion of immunosuppressive regimen, prevent early
rejection and improve prognosis.
PMID- 29343028
TI - [Pathogenesis of piriformis syndrome: a magnetic resonance imaging-based
comparison study].
AB - Objective: To assess the morphological parameters of the piriformis muscle
through magnetic resonance imaging(MRI) so as to further elucidate the
pathogenesis of piriformis syndrome (PS). Methods: From September 2015 to October
2016, 30 suspected PS patients and 30 normal controls were enrolled in this study
from the Nanfang Hospital, Southern Medical University. The possible causative
factors of the PS in the patients were obtained, and the PS patients were divided
into subgroups according to the anatomic site of the tender regions. The
parameters of the maximum thickness (cm), area (cm(2)) and the volume (cm(3)) of
the piriformis muscle of both groups were measured by MRI and were statistically
compared between the groups with the independent-sample t test so as to
investigate the pathogenesis of injured sciatic nerve. Results: Twenty-six
patients were verified with PS, unhealthy sitting postures presented in 16
patients (61.5%) and no trauma history was recorded in these patients. Fifteen
cases (57.7%) with tenderness located at the suprapiriformis foramen region (SPF
group, n=15), 11 patients (42.3%) with tenderness at the piriformis muscle (PM
group, n=11). The thickness, area and volume of the pathological side piriformis
muscle in the PM group were all significantly higher than the corresponding
indexes in the control group[(2.24+/-0.46) vs (1.66+/-0.30) cm, (14.4+/-2.2) vs
(8.8+/-2.1) cm(2,) (23.9+/-3.8) vs (15.2+/-2.6) cm(3,) respectively, t=4.699,
7.437, 8.291, all P<0.05]and were all higher remarkably than those in the SPF
group[(1.62+/-0.20) cm, (8.7+/-1.6) cm(2,) (14.1+/-4.8) cm(3,) respectively,
t=4.640, 7.631, 5.589, all P<0.05]. No significant difference was observed in the
up-mentioned indexes between the SPF and the control group (t=-0.439, -0.102,
1.083, all P>0.05). Conclusions: Tender region at the buttock indicates the
lesion site in the PS patients. The PS patients with tenderness at the
suprapiriformis region might originate from another pathogenesis independent of
piriformis muscle compression, the injury of the sciatic nerve or its branch
maybe due to the indirect crush by the soft tissue of the suprapiriformis region
under an unhealthy sitting posture.
PMID- 29343029
TI - [microRNA targeted to chronic myeloid leukemia Bcr-Abl oncogene screen using
deacetylase inhibitor].
AB - Objective: microRNA targeted to chronic myeloid leukemia Bcr-Abl oncogene were
screened using the deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA).
Methods: The proliferation inhibition effect of SAHA on chronic myeloid leukemia
K562 cell was detected by MTS method, and the optimal concentration of SAHA
reaction was determined. Western blot was used to detect the level of PARP
protein, and making sure whether SAHA induced apoptosis of K562 cell. Effect of
SAHA on Bcr-Abl Gene Transcription in K562 Cells was determined by Fluorescence
Quantitative PCR. The online software Target Scan and real-time fluorescence
quantitative PCR was used to screen Bcr-Abl-targeted microRNA. The viability of
K562 cells and Bcr-Abl transcription levels were detected by MTS method and
quantitative PCR respectively after selected microRNA were transfected into K562
cell. Results: SAHA significantly inhibited the proliferation of K562 cells and
induced apoptosis, meanwhile SAHA significantly down-regulated the
transcriptional level of Bcr-Abl gene. After treatment of K562 cells with SAHA,
two microRNA, miR-192 and miR-6816, which could target Bcr-Abl, were screened by
Target Scan and quantitative PCR. Additionally, SAHA induced the miRNAs to up
regulate 14.5 and 5.2 times, respectively. Transfection of miR-192 and miR-6816
to K562 cells significantly inhibited K562 cell viability and down-regulated the
transcriptional level of Bcr-Abl gene. Conclusion: Acetylation inhibitor SAHA
promoted the expression of miR-192 and miR-6816 in K562 cells by acetylation
regulation, miR-192 and miR-6816 further down-regulated the transcription of Bcr
Abl gene, thereby inhibiting K562 cell proliferation and induced apoptosis.
PMID- 29343031
TI - [Controversy over anticoagulation in patients with pulmonary arterial].
PMID- 29343030
TI - [Expression of high-mobility group box-I and N-methyl-D-aspartate receptor in
status epilepticus].
AB - Objective: To investigate the expression changes of high mobility group box-1
(HMGB1) and the 2B receptor of N- methyl -D- aspartate receptor (NR2B) in status
epilepticus (SE). Methods: (1) Primary hippocampal neurons from SD rats with 16
to 18 days of fetal age were cultured in vitro for 7 days, and exposed to Mg(2+)
free media for 3 hours. Those cultured neurons were randomly divided into control
group and intermittent hypoxia group. (2) SD rats with similar weight were
selected and randomly divided into control group and SE model group. The rat
model with SE was established by an intraperitoneal injection of lithium chloride
piloearpine (LI-PILO). Real-time PCR technique was used to detect the expression
of HMGB1 and NR2B mRNA. Results: In Sombati's cell model cultured in normal
concentration of oxygen, the HMGB1 mRNA expression levels were 0.005 01+/-0.000
54, 0.026 76+/-0.003 75, 0.003 52+/-0.000 33, and the NR2B mRNA expression levels
were 0.008 84+/-0.000 69, 0.012 23+/-0.000 90, 0.029 11+/-0.000 71, respectively,
at 2, 4 and 6 h; compared with the expressions of HMGB1 and NR2B mRNA at the same
time points of Sombatis cell model groups, the differences were also significant
(all P<0.05). After the successful establishment of epilepsy model, the HMGB1
mRNA expression levels were 0.000 11+/-0.000 09, 0.000 18+/-0.000 01, 0.000 11+/
0.000 01, and the NR2B mRNA expression levels were 0.196 12+/-0.009 41, 0.232
11+/-0.006 27, 0.272 48+/-0.005 84, respectively, at 6, 8 and 10 h; compared with
the expressions of HMGB1 and NR2B mRNA at the same time points of control groups,
the differences were all significant (all P<0.05). Conclusion: HMGB1 mRNA
expression levels increase at 2, 4 h, decrease at 6 h in the Sombati's cell model
in normal oxygen culture, while increase at 6, 8 h, and decrease at 10 h in LI
PILO induced rat model with SE; the NR2B mRNA relative expression increases with
time in both the Sombati's cell model in normal oxygen culture and rat model of
SE.
PMID- 29343032
TI - [Incidence and short-term outcomes of acute kidney injury in very elderly
patients].
AB - Objectives: To study the incidence, clinical characteristics, and prognostic
impact of acute kidney injury (AKI) in very elderly patients. Methods: The very
elderly patients (>=75 years) from the Geriatric Department of the Chinese PLA
General Hospital between January 2007 and December 2015 were retrospectively
enrolled. AKI was defined according to the 2012 Kidney Disease Improving Global
Outcomes (KDIGO) criteria. AKI patients were divided into survivor group and non
survivor group by their outcomes within 90 days after AKI. Prognostic survival
factors were identified using the Cox proportional hazards regression model.
Results: In total, 668 geriatric patients (39.0%) developed AKI, and 652 patients
were included in the final analysis. The median age of the cohort was 87 (84-91)
years, the majority (623 cases, 95.6%) of whom were male. Among these 652
patients, 308 (47.2%) had AKI stage 1, 164 (25.2%) had AKI stage 2, and 180
(27.6%) had AKI stage 3. Of the 652 AKI patients, the 90-day mortality was 33.6%
(219/652). Multivariate analysis by the Cox model revealed that persistent AKI
(HR=5.741, 95% CI: 3.356-9.822, P<0.001), more severe AKI stage (stage 2:
HR=3.363, 95% CI: 1.973-5.732, P<0.001 and stage 3: HR=4.741, 95% CI: 2.807
8.008, P<0.001), high blood urea nitrogen (BUN) level (HR=1.025, 95% CI: 1.014
1.037, P<0.001), low body mass index (HR=0.939, 95% CI: 0.897-0.984, P=0.008),
low mean arterial pressure (MAP) (HR=0.969, 95% CI: 0.959-0.979, P<0.001), low
prealbumin level (HR=0.935, 95% CI: 0.911-0.959, P<0.001), infection (HR=1.410,
95% CI: 1.055-1.884, P=0.020), oliguria (HR=1.948, 95% CI: 1.266-2.998, P=0.002)
were associated with 90-day mortality. Conclusions: The incidence of AKI
increases significantly with advanced age. More frequent serum creatinine (SCr)
measurements may be helpful for the early diagnosis of geriatric AKI.
Identification of risk factors might promote more intensive monitoring and early
prevention, and thus improve outcomes for very elderly patients with AKI.
PMID- 29343033
TI - [Clinical features and prognosis of 18 cases of primary lymphocytic
hypophysitis].
AB - Objective: To analyze clinical features, prognosis and treatment of lymphocytic
hypophysitis (LYH). Methods: The clinical data, treatments and outcomes of 18
cases diagnosed as LYH at Chinese PLA General Hospital between January 2001 and
July 2017 was respectively reviewed. Results: Eighteen patients with histology
proven LYH (13 females and 5 males ) were identified. All lymphocytic
adenohypophysitis (LAH) were females(n=6), two of whom were associated with
pregnancy. Eleven patients (6 females and 5 males) had lymphocytic
panhypophysitis (LPH) and one(female) had hypothalamitis. Pre-treatment
evaluation revealed that 11 patients presented with symptoms of intracranial
space-occupying lesions, 12 patients had symptoms of anterior pituitary hormone
deficiencies, and 12 patients had central diabetes insipidus (CDI). All patients
had space-occupying lesions on magnetic resonance imaging (MRI), which were
symmetrically enlarged and homogenously enhanced with or without pituitary stalk
thickening. Before or after surgery, 11 patients received immunosuppressant
therapy or radiotherapy to alleviate space-occupying effect. After 4-204 months
follow-up, 5 patients had a relapse and received immunosuppressants, radiotherapy
or surgery to achieve remission. Full recovery (both symptomatic and
radiographic) was seen in 6 patients, and 11 patients maintained stable
replacement therapy. Conclusions: LYH presents with acute space-occupying effects
such as headache, visual disturbances, hypopituitarism, CDI and mild
hyperprolactinemia, especially with characteristic radiographic manifestations.
Usually, surgery reliably establishes diagnosis, and immunosuppressant therapy is
a necessity. On the whole, LYH has a good prognosis.
PMID- 29343034
TI - [A study on the effects and safety of sequential humidified high flow nasal
cannula oxygenation therapy on the COPD patients after extubation].
AB - Objective: To investigate and compare the effect and safety of nasal high-flow
oxygen therapy (HFNCO) and noninvasive ventilation (NIV) therapy after extubation
in patients with chronic obstructive pulmonary disease (COPD). Methods: All COPD
patients subjected to mechanical ventilation in the Emergency Intensive Unit of
the First Affiliated Hospital of Zhejiang University during January 2015 to June
2016 were included in the study. The patients were divided into two groups after
extubation and HFNCO and NIV were adopted on each group respectively. Clinical
indexes including the patients' general condition, blood gas analysis and
pulmonary function before and after extubation, ratio of re-intubation and CT
grades were collected and analyzed. Results: There was no significant difference
in the incidence of aspiration (4.8% vs 8.3%), pressure sores (0 vs 8.3%) and
delirium (4.8% vs 12.5%) between the two groups (all P>0.05). At 12 h after
extubation, the oxygenation index of NIV group was significantly higher than that
of the HFNCO group (265+/-29 vs 297+/-33; P<0.05), while no significant
difference in PCO(2) (P>0.05). For 24 h and 72 h after extubation, there was no
statistically significant difference in oxygenation index and PCO(2) between the
both groups (P>0.05). The intensive care unit (ICU) retention time in HFNCO group
was significantly lower than that in NIV group (13.7+/-0.8 vs 15.2+/-0.5;
P<0.05). In addition, no significant difference between the two groups in
mortality and re-intubation rate at 28 d (P>0.05) was observed. Conclusion: HFNCO
is effective and safe in the treatment of COPD patients after extubation, and it
is hence valuable for further clinical application.
PMID- 29343035
TI - [Comparison of percutaneous endoscopic lumbar discectomy versus transforaminal
lumbar interbody fusion in treating upper lumbar disc herniation].
AB - Objective: To compare the efficacy of percutaneous endoscopic transforaminal
discectomy (PTED) and transforaminal lumbar interbody fusion (TLIF) in the
treatment of high lumbar disc herniation. Methods: The clinical data of patients
with high lumbar disc herniation from February 2010 to February 2015 were
retrospective analyzed. According to the inclusion criteria, a total of 63 cases
were enrolled, including PTED group 33 cases, TLIF group 30 cases. The
improvement of the two groups before and after surgery was assessed by visual
analogue scale (VAS) and Oswestry dysfunction index (ODI). The operative time,
intraoperative blood loss, drainage volume at 48 h postoperatively,
hospitalization time, number of fluoroscopy, complication, recurrence rate and
postoperative recovery were compared between the two groups. The follow-up period
was 12 to 33 months. Results: The operation time, intraoperative blood loss,
drainage amount and hospitalization time in PTED group were significantly less
than those in TLIF group[(71+/-19) vs (121+/-22) min, (30+/-21) vs (317+/-50) ml,
0 vs (93+/-29) ml, (3.5+/-1.9) vs (12.5+/-2.1) d]. The number of fluoroscopy in
PTED group was significantly higher than TLIF group[(16.2+/-8.3) vs (6.7+/
4.2)](all P<0.05). There was no significant difference in VAS score and ODI
improvement rate between the two groups after operation (both P>0.05). There was
no significant difference between the two groups in the excellent rate of surgery
and the recurrence rate (both P>0.05). Conclusions: PTED has the advantages of
less trauma and bleeding, rapid postoperative recovery in the treatment of upper
lumbar disc herniation compared with TLIF, and the curative effect and recurrence
rate are similar with TLIF. Therefore, PTED is an effective method for the
treatment of upper lumbar disc herniation.
PMID- 29343037
TI - [Mechanisms of fosfomycin resistance of extended-spectrum beta-lactamases
producing Escherichia coli and Klebsiella pneumoniae].
AB - Objective: To study the in vitro activity of fosfomycin to extended-spectrum beta
lactamases (ESBLs)-producing Escherichia coli and Klebsiella pneumoniae and to
explore the mechanisms of fosfomycin resistance. Methods: A total of 1 052 ESBLs
producing E. coli(ESBL-EC) and K. pneumoniae(ESBL-KP) isolates were collected
from bloodstream infections of 28 hospitals of 22 provinces and municipalities,
which were stored by our laboratory.Minimum inhibitory concentrations (MICs) of
fosfomycin against these clinical isolates were determined by agar dilution
methods according to the Clinical and Laboratory Standards Institute
(CLSI)(2015). The genes related to fosfomycin resistance were confirmed by
Polymerase Chain Reaction (PCR) and sequencing. Results: The susceptibility rates
of ESBL-EC and ESBL-KP isolates to fosfomycin were 91.3% (818/896) and 91.7%
(143/156), respectively. A total of 91 fosfomycin-non-susceptible isolates were
detected, of which 73 (80.2%) isolates carried fosA3 genes.Amongst 18 fosA3
negative isolates, 16 isolates were detected to have chromosomal mutations or
insertion inactivation, while the rest two isolates had not been detected any
resistant mechanisms. Conclusions: Fosfomycin shows great in vitro antimicrobial
activity to ESBL-EC and ESBL-KP. The primary mechanism of fosfomycin-non
susceptible isolates is fosA3 gene.Chromosomal mutations may also involve in the
fosfomycin resistance.
PMID- 29343036
TI - [Analysis of genotype and hematological phenotype of 14 patients with
coinheritance HKalphaalpha and South-East deletion thalassemia].
AB - Objective: To analyze the genotype-phenotype correlations among those thalassemia
samples with the presence of -alpha(3.7,) --(SEA) and normal alpha(2) alleles on
their alpha-globin gene clusters. Methods: Fourteen patients(including 1fetus, 4
males and 9 females, aged 0- 56 years old)who were suspected diagnosed by
hematologic analysis and genetic testing among 16 080 participants in our
laboratory since from August 2011 to August 2016, were enrolled. Complete blood
cell count was performed on XE4000i automatic hemocyte analyzer. HbA0, HbF and
HbA2 were tested by high performance liquid chromatography (HPLC). Gap-PCR was
adopted to detect three common deletional thalassemia deletions. Reverse dot-blot
(RDB) assay was applied for detecting 17 common beta-globin gene mutations and
three common non-deletional alpha(2) gene mutations. Two-round nested PCR assay
was established to detect the genotype of HKalphaalpha in alpha-thalassemia.
Results: Fourteen cases were identified as HKalphaalpha/--(SEA) (14/16 080),
including a pedigree and a rare case of HKalphaalpha/--(SEA) co-inheritance with
IVS-II-654(C->T) heterozygote. In HKalphaalpha/--(SEA) thalassemia group, mean
cell volume(MCV) was (69.54+/-5.92)fl, and mean cell hemoglobin(MCH) was(22.11+/
2.22)pg and hemoglobin(Hb) was (117.64+/-18.14) g/L. Compared with normal group,
MCV, MCH and Hb in HKalphaalpha/--(SEA) thalassemia group, was significantly
decreased(P<0.05). There were no significant differences between alpha
thalassemia control group(--(SEA) /alphaalpha) in most hematological parameters
(P>0.05). Conclusion: The two-round nested PCR could effectively detect the
HKalphaalpha/--(SEA) genotype. The hematologic characteristics changed
significantly in HKalphaalpha/--(SEA) group compared with HbH thalassemia and
normal group. The genotype and phenotype non-correlation in patients with alpha
thalassemia should especially be causious to avoid a misdiagnosis of genetic
tests, especially in prenatal diagnosis.
PMID- 29343038
TI - [Diagnostic value of albumin-bilirubin grade combined with serum ammonia in
cirrhosis with hepatic encephalopathy].
AB - Objective: To explore the value of albumin-bilirubin (ALBI) grade combined with
serum ammonia in the diagnosis of cirrhosis with hepatic encephalopathy (HE).
Methods: The serum level of total bilirubin(TBIL), albumin( ALB )and blood
ammonia were detected in 139 patients including 73 cirrhosis patients without HE
and 66 cirrhosis patients with HE from January 2015 to January 2017 in Beijing
You'an Hospital, and the relationship between ALBI and blood ammonia value and
Child grade and hepatic encephalopathy was analyzed. Results: The level of ALBI
and blood ammonia were more and more higher with the increase of Child grade, the
level of ALBI in Child A, B and C were -2.3+/-0.6, -1.7+/-0.5, -0.9+/-0.4, and
there was a statistically significant(F=125.100, P<0.001). The blood ammonia
concentration in Child A, B and C were(42.6+/-16.0), (56.1+/-31.2), (69.8+/-34.7)
MUmol/L, and there was a statistically significant(F=7.400, P<0.001). The level
of ALBI was higher with the increase of model for end-stage liver disease (MELD)
grade, and there was a positive correlation(r=0.547, P<0.001). The ALBI value in
the HE group was higher than the cirrhosis patients without HE((-1.1+/-0.5)vs(
1.6+/-0.7)), and the difference was statistically significant (t=5.244, P<0.001).
Level of blood ammonia in the HE group was(83.6+/-39.5)MUmol/L, which was higher
than the level of cirrhosis patients without HE(42.9+/-17.0)MUmol/L, and the
difference was statistically significant (t=8.130, P<0.001) . When ALBI and blood
ammonia were combined, the ROC curve area was 0.911, the sensitivity was 93.9%,
the specificity was 93.2%. Conclusion: There is a significant diagnosis value and
high clinical application when ALBI is combined with blood ammonia to diagnose HE
.
PMID- 29343039
TI - [Development of a Chinese nomogram based on muti-parametric magnetic resonance
for predicting the probability of prostate cancer in patients after initial
negative biopsy].
AB - Objective: To develop a predictive nomogram based on multi-parametric magnetic
resonance imaging (mpMRI) information to identify men more likely to have a
cancer diagnosed on repeat prostate biopsy. Methods: The clinical data of 237
patients who received repeat prostate biopsy after initial negative biopsy from
Department of Urology of Peking University First Hospital between January 2001
and August 2016 was reviewed. Patient age, body mass index (BMI), serum total
prostate-specific antigen (PSA), percent free PSA (f/t), prostate volume (PV),
PSA density (PSAD), PSA velocity (PSAV), digital rectal examination (DRE),
transrectal ultrasound (TRUS)and mpMRI results were included in the univariate
and multivariate analysis. A nomogram was developed using selected variables and
the area under the receiver operating characteristic (ROC) curve was calculated
as a measure of discrimination. Results: A total of 76 patients (32.07%) had
prostate cancer (PCa) detected on repeat biopsy. Based on univariate and
multivariate logistic regression analysis, the patient age, PSA, PV, DRE and
mpMRI results were independent predictors for the diagnosis of PCa on repeat
biopsy. The current nomogram performed well (AUC=0.910) and showed excellent
calibration. Conclusions: Multi-parametric magnetic resonance imaging combined
with age, PSA, PV and DRE can predict the probability of PCa in patients with
initial negative biopsy. The nomogram might help in decision-making for men with
prior benign histology before the performance of repeat biopsy.
PMID- 29343040
TI - [Effect of picroside II on the expression of mitochondrial VDAC1 after cerebral
ischemia/reperfusion in rats].
AB - Objective: To explore the effect of picroside II on the expression of
mitochondrial voltage-dependent anion channel 1 (VDAC1) in rats after cerebral
ischemiareperfusion. Methods: A total of 70 Wistar rats models with middle
cerebral artery occlusionreperfusion (MCAO/R) were randomly divided into the sham
group, model group, picroside (Picr) group, ruthenium red (RuR) group, RuR+ Picr
group, Spermine (Sper) group, Sper+ Picr group (n=10 per group). Modified
neurological severity scale (mNSS) was used to evaluated the neurobehavioral
function, the expression of reactive oxygen species (ROS) in brain tissues were
measured by enzyme-linked immunosorbent assay (ELISA), the morphology of brain
tissues was observed by hematoxylin-eosin (HE) staining, the apoptotic cells were
counted by terminal deoxynucleotidyl transferase dUTP nick end labeling assay
(TUNEL), and the expressions of VDAC1 and endonuclease G (EndoG) were determined
by immunohistochemical assay and Western blot. Results: Compared with the shame
group, the mNSS scores (9.6+/-1.9), the expression of ROS[(47.6+/-2.7)U/ml], the
apoptosis of neuron(23.8+/-2.8), and the expressions of VDAC1(0.94+/-0.06) and
EndoG in cytoplasm (0.76+/-0.06) and nuclei(0.75+/-0.06)were enhanced in the
model group (all P<0.05). The Picr group had obviously decreased mNSS scores
(5.7+/-0.9), ROS expression[(35.6+/-2.2)U/ml], number of apoptotic cells (14.5+/
2.1), VDAC1 (0.63+/-0.06) and EndoG in cytoplasm (0.34+/-0.05) and nuclei (0.31+/
0.06)expressions compared to the model group (P<0.05). Conclusion: Picroside II
could attenuate cerebral I/R injury by down-regulating the expression of VDAC1
and inhibiting the EndoG release from mitochondria into cytoplasm.
PMID- 29343041
TI - Forgoing life-sustaining treatments in the ICU. To withhold or to withdraw: is
that the question?
AB - In the last decades, mortality from severe acute illnesses has considerably
declined thanks to the advances in intensive care medicine. Meanwhile, critical
care physicians realized that life-sustaining treatments (LST) may not be
appropriate for every patient, and end-of-life care in the Intensive Care Unit
(ICU) started to receive growing attention. Most deaths occurring in the ICU now
follow a decision to forgo life-sustaining treatments (DFLST), which can be
implemented either by withdrawing (WDLST) or withholding (WHLST) life-sustaining
treatments. Despite the broad consensus about the equivalence of the two
practices from an ethical point of view, the issue of the best option between
WDLST and WHLST constantly gives rise to controversies in clinical practice. This
review is not intended to take a stand for or against WDLST or WHLST. Based on
available evidence, the definitions of the two practices are first presented.
Secondly, the preferences of ICU physicians towards WDLST and WHLST are examined.
Finally, some arguments are offered outlining pros and cons of WDLST and WHLST,
stressing that the clinician's attention should focus on an early and thorough
recognition of patients in need of a DFLST, rather than on the theoretical
strength and weakness of the two practices. This approach will enable physicians
to make informed decisions on how to implement the limitation of LSTs,
considering the patients' clinical conditions and preferences, the circumstances
and needs of their families.
PMID- 29343042
TI - Harlequin syndrome as a rare complication after epidural anesthesia in an
obstetric patient.
PMID- 29343043
TI - Mandibular pain: an uncommon radiation for cervical facet joint syndrome.
PMID- 29343044
TI - Bronchial blocker positioning: learning curve and confidence in its use.
AB - BACKGROUND: Despite being simple and safe to use and cheap, EZ blocker (EZB)
remains underused probably because it requires particular skills in recognizing
airway and in using fiber-bronchoscopy to check the exact position of their
cuffs. Thus, we planned an education training program on the use of EZB for
novices in anesthesia and evaluated the number of procedures required for the
acquisition of the skills of this technique. METHODS: The educational training
program included three different phases as follows. The first phase included a
lecture on the utility of one-lung ventilation in thoracic surgery, on the use of
the fiber- bronchoscopy and on the characteristics of EZB. The second phase
consisted in a practical teaching course performed on a manikin model to acquire
the skills in EZB. The third phase was a clinical training where each participant
performed a defined number in patients scheduled for thoracic surgery procedures.
The acquisition of dexterity and satisfaction were then statistically valuated.
RESULTS: The dexterity in placing EZB significantly increased after six attempts
(P<0.1). Participants acquired skills in correcting position EZB after 15
attempts. Participants increased their level of confidence with EZB (score 5.7+/
1.3) and were highly satisfied with the training received (score 5.8+/-1.6).
CONCLUSIONS: EZB is a valid strategy for obtaining one lung ventilation. Thus, it
should be included in the armamentarium of all anesthetists interested in the
field of thoracic surgery. Our teaching course seems to be a valuable method to
instill easily and speedily in training novices in anesthesia the skills in
placing EZB.
PMID- 29343045
TI - What kind of evidence are we looking for to justify the use of ECCO2R?
PMID- 29343046
TI - The real role of the PEEP in operating room: pros & cons.
PMID- 29343047
TI - Acute esophageal necrosis in critically ill patients: consider this possibility!
PMID- 29343048
TI - Physiology, intervention, and outcome: three critical questions about cerebral
tissue oxygen saturation monitoring.
AB - The balance between cerebral tissue oxygen consumption and supply can be
continuously assessed by cerebral tissue oxygen saturation (SctO2) monitor. A
construct consisting of three sequential questions, targeting the physiology
monitored, the intervention implemented, and the outcomes affected, is proposed
to critically appraise this monitor. The impact of the SctO2-guided care on
patient outcome was examined through a systematic literature search and meta
analysis. We concluded that the physiology monitored by SctO2 is robust and
dynamic, fragile (prone to derangement), and adversely consequential when
deranged. The inter-individual variability of SctO2 measurement advocates for an
intervention threshold based on a relative, not absolute, change. The intra
individual variability has multiple determinants which is the foundation of
intervention. A variety of therapeutic options are available; however, none are
100% efficacious in treating cerebral dys-oxygenation. The therapeutic efficacy
likely depends on both an appropriate differential diagnosis and the functional
status of the regulatory mechanisms of cerebral blood flow. Meta-analysis based
on five randomized controlled trials suggested a reduced incidence of early
postoperative cognitive decline after major surgeries (RR= 0.53; 95% CI: 0.33
0.87; I2 =82%; P=0.01). However, its effects on other neurocognitive outcomes
remain unclear. These results need to be interpreted with caution due to the high
risks of bias. Quality RCTs based on improved intervention protocols and
standardized outcome assessment are warranted in the future.
PMID- 29343049
TI - The ultrasound-guided mid-point transverse process to pleura block for
postoperative analgesia in video-assisted thoracoscopic surgery.
PMID- 29343050
TI - Phantom limb pain successfully treated with scrambler therapy.
PMID- 29343051
TI - Ketamine and remote hyperalgesia.
PMID- 29343052
TI - Implications of oxygenation variations in ventilated patients with respiratory
infections.
PMID- 29343053
TI - Staphylococcus aureus producing Panton-Valentine Leukocidin: an emerging problem
in Italian ICUs.
PMID- 29343054
TI - Gender and sepsis: first step of personalized medicine?
PMID- 29343055
TI - Genetically Encoded Circuit for Remote Regulation of Cell Migration by Magnetic
Fields.
AB - Magnetoreception can be generally defined as the ability to transduce the effects
of a magnetic field into a cellular response. Magnetic stimulation at the
cellular level is particularly attractive due to its ability for deep penetration
and minimal invasiveness, allowing remote regulation of engineered biological
processes. Previously, a magnetic-responsive genetic circuit was engineered using
the transient receptor potential vanilloid 1 (TRPV1) and the iron containing
ferritin protein (i.e., the TF circuit). In this study, we combined the TF
circuit with a Ca2+ activated RhoA protein (CaRQ) to allow a magnetic field to
remotely regulate cell migration. Cells expressing the TF circuit and CaRQ
exhibited consistent dynamic protrusions, leading to migration along a porous
membrane, directed spreading in response to a magnetic field gradient, as well as
wound healing. This work offers a compelling interface for programmable
electrical devices to control the migration of living systems for potential
applications in cell-based therapy.
PMID- 29343056
TI - A Phosphorescent Trinuclear Gold(I) Pyrazolate Chemosensor for Silver Ion
Detection and Remediation in Aqueous Media.
AB - We report a phosphorescent chemosensor based on a trinuclear Au(I) pyrazolate
complex or [Au(3-CH3,5-COOH)Pz]3 (aka Au3Pz3) stabilized in aqueous chitosan (CS)
polymer media. Au3Pz3 is synthesized in situ within aqueous CS media at pH ~ 6.5
and room temperature (RT). Au3Pz3 exhibits strong red emission (lambdamax ~ 690
nm) in such solutions. On addition of silver salt to Au3Pz3/CS aqueous media, a
bright-green emissive adduct (Au3Pz3/Ag+) with a peak maximum within 475-515 nm
is developed. The silver adduct exhibits a 4-fold increase in quantum yield (0.19
+/- 0.02) compared to Au3Pz3 alone (0.05 +/- 0.01), along with a corresponding
increase in phosphorescence lifetime. With almost zero interference from 15 other
metal ions tested, Au3Pz3 exhibits extreme selectivity for Ag+ with nM/ppb
detection limits (6.4-72 ppb, depending on %CS and on the sensitivity basis being
a signal-to-noise ratio (S/N) = 3 or a baseline-corrected signal change = 10%).
Au3Pz3 exhibits sensitivity to higher concentrations (>1 mM) of other metal ions
(Tl+/Pb2+/Gd3+). The sensing methodology is simple, fast, convenient, and can
even be detected by the naked eye. On addition of ethylenediaminetetraacetic acid
(EDTA), the red Au3Pz3 emission can be restored. Au3Pz3 and its silver adduct
retain their characteristic photophysical properties in thin film forms.
Remarkable photostability with <7% photobleaching after 4 h of UV irradiation is
attained for Au3Pz3 solutions or thin films.
PMID- 29343057
TI - Cu-T1 Sensor for Versatile Analysis.
AB - Conventional magnetic sensors usually employ Fe-based magnetic materials as
signal probes. In this work, we find that Cu(II) is also a useful longitudinal
relaxation time (T1) signal-based magnetic probe. We adopt
bathocuproinedisulfonic acid disodium salt hydrate (BCS) to chelate Cu(I) and
form a stable Cu(I)-BCS complex in aqueous solution and find the significant
difference in the T1 value of water protons between Cu(II) aqueous solution and
Cu(I)-BCS complex aqueous solution. Redox reaction can convert Cu(II) to Cu(I)
followed by the complexation of BCS, which results in apparent change of T1 that
can serve as magnetic signal readout, which is the basis of this Cu-T1 sensor.
Many redox reactions between Cu(II) and Cu(I) allow this Cu-T1 sensor to not only
realize "one-step mode" assay such as ascorbic acid, protein, and alkaline
phosphatase but also enable "multi-step mode" immunoassay, such as
biomacromolecules and small molecules. This Cu-T1 sensor employs Cu ion as signal
readout, providing an alternative tool for biochemical analysis.
PMID- 29343058
TI - Biosynthesis of Long-Chain N-Acyl Amide by a Truncated Polyketide Synthase
Nonribosomal Peptide Synthetase Hybrid Megasynthase in Fungi.
AB - Truncated iterative polyketide synthase-nonribosomal peptide synthetase (PKS
NRPS) megasynthases in which only the C domain is present are widespread in
fungi, yet nearly all members have unknown functions. Bioinformatics analysis
showed that the C domains of such PKS-C enzymes are noncanonical due to
substitution at the second histidine in the active site HHxxxDG motif. Here, we
used genome mining strategy to characterize a cryptic PKS-C hybrid from
Talaromyces wortmanii and discovered the products are reduced long-chain
polyketides amidated with a specific omega-amino acid 5-aminopentanoic acid
(5PA). The wortmanamides resemble long-chain N-acyl-amide signaling lipids that
target diverse receptors including GPCRs. The noncanonical C domain of this PKS-C
hybrid was also demonstrated to be a bona fide condensation domain that
specifically selects 5PA and catalyzes amidation to release polyketide chain.
PMID- 29343059
TI - Top-Down Characterization of Heavily Modified Histones Using 193 nm Ultraviolet
Photodissociation Mass Spectrometry.
AB - The characterization of protein post-translational modifications (PTMs) remains a
significant challenge for traditional bottom-up proteomics methods owing to the
lability of PTMs and the difficulty of mapping combinatorial patterns of PTMs
based on analysis of small peptides. These shortcomings have accelerated interest
in top-down MS/MS methods that focus on analysis of intact proteins. Simultaneous
mapping of all PTMs requires extensive sequence coverage to confidently localize
modifications. 193 nm ultraviolet photodissociation (UVPD) has been shown to
generate unparalleled sequence coverage for intact proteins compared to
traditional MS/MS methods. This study focuses on identification and localization
of PTMs of histones by UVPD, higher-energy collisional dissociation (HCD), and
the hybrid method electron-transfer/higher-energy collision dissociation (EThcD)
via a high throughput liquid chromatography-mass spectrometry strategy. In total,
over 500 proteoforms were characterized among these three activation methods with
46% of the identifications found in common by two or more activation methods.
EThcD and UVPD afforded more extensive characterization of proteoforms than HCD
with average gains in sequence coverage of 15% and C-scores that doubled on
average.
PMID- 29343060
TI - Direct CO2 Addition to a Ni(0)-CO Species Allows the Selective Generation of a
Nickel(II) Carboxylate with Expulsion of CO.
AB - Addition of CO2 to a low-valent nickel species has been explored with a newly
designed acriPNP pincer ligand (acriPNP- = 4,5-bis(diisopropylphosphino)-2,7,9,9
tetramethyl-9H-acridin-10-ide). This is a crucial step in understanding
biological CO2 conversion to CO found in carbon monoxide dehydrogenase (CODH). A
four-coordinate nickel(0) state was reliably accessed in the presence of a CO
ligand, which can be prepared from a stepwise reduction of a cationic
{(acriPNP)Ni(II)-CO}+ species. All three Ni(II), Ni(I), and Ni(0) monocarbonyl
species were cleanly isolated and spectroscopically characterized. Addition of
electrons to the nickel(II) species significantly alters its geometry from square
planar toward tetrahedral because of the filling of the dx2-y2 orbital.
Accordingly, the CO ligand position changes from equatorial to axial, ?N-Ni-C of
176.2(2) degrees to 129.1(4) degrees , allowing opening of a CO2 binding site.
Upon addition of CO2 to a nickel(0)-CO species, a nickel(II) carboxylate species
with a Ni(eta1-CO2-kappaC) moiety was formed and isolated (75%). This reaction
occurs with the concomitant expulsion of CO(g). This is a unique result markedly
different from our previous report involving the flexible analogous PNP ligand,
which revealed the formation of multiple products including a tetrameric cluster
from the reaction with CO2. Finally, the carbon dioxide conversion to CO at a
single nickel center is modeled by the successful isolation of all relevant
intermediates, such as Ni-CO2, Ni-COOH, and Ni-CO.
PMID- 29343061
TI - Analyzing and Tuning Ribozyme Activity by Deep Sequencing To Modulate Gene
Expression Level in Mammalian Cells.
AB - Self-cleaving ribozymes, in combination with aptamers and various classes of
RNAs, have been heavily engineered to create RNA devices to control gene
expression. Although understanding of sequence-function relationships of
ribozymes is critical for such efforts, our current knowledge of self-cleaving
ribozymes is mostly limited to the results from small scale mutational studies
performed under different conditions, or qualitative results of mutate-and-select
experiments that may contain experimental biases. Here, we applied our strategy
based on deep sequencing to comprehensively assay a large number of mutants to
systematically examine the effect of the P4 stem sequence on the activity of an
HDV-like ribozyme. We discovered that the ribozyme activity is highly sensitive
to the sequence and the apparent stability of the varied positions. Furthermore,
we demonstrated that the collection of the ribozyme variants with different
activities can be used as a convenient device to fine-tune the level of gene
expression in mammalian cells.
PMID- 29343062
TI - Tailored Waveform of Dielectric Barrier Discharge to Control Composite Thin Film
Morphology.
AB - Nanocomposite thin films of TiO2 in a polymer-like matrix are grown in a
filamentary argon (Ar) dielectric barrier discharge (DBD) from a suspension of
TiO2 nanoparticles in isopropanol (IPA). The sinusoidal voltage producing the
plasma is designed to independently control the matrix growth rate and the
transport of nanoparticle (NP) aggregates to the surface. The useful FSK
(frequency shift keying) modulation mode is chosen to successively generate two
sinusoidal voltages: a high frequency of 15 kHz and a low frequency ranging from
0.5 to 3 kHz. The coating surface coverage by the NPs and the thickness of the
matrix are measured as a function of the FSK parameters. The duty cycle between
these two signals is varied from 0 to 100%. It is observed that the matrix
thickness is mainly controlled by the power of the discharge, which largely
depends on the high-frequency value. The quantity of NPs deposited in the
composite thin film is proportional to the duration of the low frequency applied.
The FSK waveform has a double modulation effect, allowing us to obtain a uniform
coating as the NPs are not affected by the high frequency and the matrix growth
rate is limited when the low frequency is applied. When it is close to a
frequency limit, the low frequency acts like a filter for the NP aggregates. The
higher the frequency, the smaller the size of the aggregates transferred to the
surface. By changing only the FSK modulation parameters, the thin film can be
switched from superhydrophobic to superhydrophilic, and under suitable
conditions, a nanocomposite thin film is obtained.
PMID- 29343063
TI - Why Does CuFeS2 Resemble Gold?
AB - While several potential applications of CuFeS2 quantum dots have already been
reported, doubts regarding their optical and physical properties persist. In
particular, it is unclear if the quantum dot material is metallic, a degenerately
doped semiconductor, or else an intrinsic semiconductor material. Here we examine
the physical properties of CuFeS2 quantum dots in order to address this issue.
Specifically, we study the bump that is observed in the optical spectra of these
quantum dots at ~500 nm. Using a combination of structural and optical
characterization methods, ultrafast spectroscopy, as well as electronic structure
calculations, we ascertain that the unusual purple color of CuFeS2 quantum dots
as well the golden luster of CuFeS2 films arise from the existence of a plasmon
resonance in these materials. While the presence of free carriers causes this
material to resemble gold, surface treatments are also described to suppress the
plasmon resonance altogether.
PMID- 29343064
TI - Generalized Theory for the Timescale of Molecular Electronic Decoherence in the
Condensed Phase.
AB - We introduce a general theory of electronic decoherence for molecules in the
condensed phase that captures contributions coming from pure dephasing effects,
electronic transitions among diabatic states, and their interference. The theory
is constructed by taking advantage of a recently developed [ J. Phys. Chem. Lett.
2017 , 8 , 4289 - 4294 ] general expression for decoherence times that is based
on an early time expansion of the purity dynamics and extends early electronic
decoherence models based on pure dephasing ideas. Using this theory, we construct
the decoherence time for the displaced harmonic oscillator model amended with
constant and linear diabatic couplings, which is a widely used model of the
photoexcited dynamics of molecules. The validity of the short-time expansion is
demonstrated by the quantitative agreement of the theory with exact numerical
computations of the decoherence dynamics obtained using the hierarchical equation
of motion method. These developments offer a rigorous understanding of early time
electronic decoherence processes that accompany basic molecular events and
demonstrate that electronic transitions among diabatic states play a major role
in the decoherence dynamics.
PMID- 29343065
TI - Perfect Adaptation and Optimal Equilibrium Productivity in a Simple Microbial
Biofuel Metabolic Pathway Using Dynamic Integral Control.
AB - The production of complex biomolecules by genetically engineered organisms is one
of the most promising applications of metabolic engineering and synthetic
biology. To obtain processes with high productivity, it is therefore crucial to
design and implement efficient dynamic in vivo regulation strategies. We consider
here the microbial biofuel production model of Dunlop et al. (2010) for which we
demonstrate that an antithetic dynamic integral control strategy can achieve
robust perfect adaptation for the intracellular biofuel concentration in the
presence of poorly known network parameters and implementation errors in certain
rate parameters of the controller. We also show that the maximum equilibrium
extracellular biofuel productivity is fully defined by some of the network
parameters and, in this respect, it can only be achieved when all the
corresponding parameters are perfectly known. Since this optimum is a network
property, it cannot be improved by the use of any controller that measures the
intracellular biofuel concentration and acts on the production of pump proteins.
Additional intrinsic fundamental properties for the process are also unveiled,
the most important ones being the existence of a conservation relation between
the productivity and the toxicity, a low sensitivity of the optimal productivity
with respect to a poor implementation of the set-point for the intracellular
biofuel, and a strong intrinsic robustness property of the optimal productivity
with respect to poorly known parameters. Taken together, these results
demonstrate that a high and robust equilibrium rate of production for the
extracellular biofuel can be achieved when the parameters of the model are poorly
known and those of the controllers are poorly implemented. Finally, several
advantages of the proposed dynamic strategy over a static one are also
emphasized.
PMID- 29343066
TI - Kane Fermion in a Two-Dimensional pi-Conjugated Bis(iminothiolato)nickel
Monolayer.
AB - Massless Kane fermions revealed in zinc-blende semiconductors have recently
gained interest in the broad study of relativistic materials. In particular, two
dimensional (2D) Kane fermions were expected to be hybrids of pseudospin-1 and
1/2 Dirac fermions. Based on first-principles calculations, we demonstrated that
2D Kane fermions can be realized in a recently synthesized metal-organic
framework, namely, bis(iminothiolato)nickel monolayer. A slight compression takes
the system from a semimetal to a semiconductor. At the critical strain of ~1%,
the upper and lower conical bands linearize and touch at a single point
intersecting a flat band, showing the same dispersion as the pseudospin-1 Dirac
Weyl systems. We adopted a tight-binding Hamiltonian of a line-centered honeycomb
lattice to reveal the origins and topology of the electronic band structure. The
coexistence of Kane-type and Dirac-type spectra in the bis(iminothiolato)nickel
monolayer is expected to benefit the study of multi quasiparticle effects.
PMID- 29343068
TI - Spotlights: Volume 9, Issue 2.
PMID- 29343067
TI - Practical Efficiency Limit of Methylammonium Lead Iodide Perovskite (CH3NH3PbI3)
Solar Cells.
PMID- 29343069
TI - At the Cutting Edge of Surface Science: A Tribute to Miquel B. Salmeron.
PMID- 29343070
TI - Autobiography of Miquel B. Salmeron.
PMID- 29343071
TI - Selected Publications of Miquel B. Salmeron.
PMID- 29343072
TI - Colleagues of Miquel B. Salmeron.
PMID- 29343073
TI - Human Semen or Seminal Plasma Does Not Enhance HIV-1BaL Ex Vivo Infection of
Human Colonic Explants.
AB - To determine whether human whole semen (WS) and seminal plasma (SP) either
previously frozen or freshly acquired altered ex vivo infectibility of human
colonic explants or was associated with histology or toxicity changes, which may
influence mucosal HIV-1 transmission in vivo. Pooled human semen samples were
freshly obtained from study volunteers (never frozen) and from commercial sources
(frozen/thawed). Endoscopically acquired rectal biopsies were evaluated for
toxicity following titered ex vivo WS/SP exposure by histological grading and by
MTT assay. The ex vivo HIV-1 biopsy challenge model was used to evaluate effects
of exposure to either previously frozen or freshly acquired WS/SP on HIVBaL
infectibility at a range of viral inocula (104-100 TCID50). To evaluate the
effects at lower viral inocula of HIV-1 (10-2-102), experiments in the presence
or absence of WS/SP were also performed utilizing TZM-bl cells. MTT assays and
histological scoring demonstrated no tissue degradation of biopsies when exposed
for 2 h to concentrations of 10% or 100% of either fresh or previously frozen
WS/SP. Ex vivo biopsy HIV-1 challenge experiments showed no differences in the
presence of freshly acquired or previously frozen/thawed WS/SP compared with
control; no differences were seen with lower infectious titers on TZM-bl cells.
Within the limits of assay sensitivity and variability, these data show no
toxicity or significant enhancement of HIV-1 infectibility of human rectal mucosa
using the colorectal explant model with either pooled fresh or frozen/thawed
nonautologous human semen.
PMID- 29343074
TI - Understanding the influence of antipsychotic drugs on global methylation events
and its relevance in treatment response.
AB - AIM: The present study intends to evaluate whether antipsychotic drugs can
modulate the host epigenome and if so whether drug-induced epigenetic modulation
can explain the heterogeneity in drug response. METHODS: Present study was
conducted in in vitro cells and significance of these in vitro observations was
further evaluated in a clinical setting, between drug responsive and
nonresponsive schizophrenia patients. A number of DNA modifications were assessed
at global level using 5-methylcytosine, 5-hydroxymethylcytosine and 5
formylcytosine followed by evaluating the expression of epigenetic modifier genes
and their crosstalk with miRNAs. RESULTS: In vitro data demonstrated that
antipsychotic drugs induce epigenetic response by downregulating miRNA that
target DNA methyltransferases, resulting in global hypermethylation. Similar
trend was observed in clinical setting too and alterations were markedly
associated with drug response rather than disease pathogenesis. CONCLUSION: Study
demonstrates that antipsychotic drugs can influence host methylome and thereby
indicating its role in mediating a strong pharmacoepigenomic response.
PMID- 29343076
TI - High Loading Dose of Atorvastatin for the Prevention of Serum Creatinine and
Cystatin C-Based Contrast-Induced Nephropathy Following Percutaneous Coronary
Intervention.
AB - The aim of this study is to assess the efficacy of high-dose atorvastatin on the
prevention of contrast-induced nephropathy (CIN) in patients with acute coronary
syndrome (ACS) undergoing percutaneous intervention and observe the incidence of
cystatin C (CyC)-based CIN. A total of 496 patients with ACS were randomly
assigned to either the control group (247 patients receiving conventional dose
atorvastatin 10 mg daily from 1 day before to 3 days after contrast
administration) or the high-dose atorvastatin group (249 patients receiving
atorvastatin 40 mg daily for the same perioperative period). The baseline
characteristics of the 2 groups were similar. The primary end point of serum
creatinine (SCr)-based CIN occurred in 31 patients in the control group and 16
patients in the high-dose atorvastatin group (12.6% vs 6.4%; P = .02). Cystatin C
based CIN developed in 90 patients in the control group and 46 patients in the
high-dose atorvastatin group (36.4% vs 18.5%; P < .001). A multivariable analysis
revealed that high-dose atorvastatin was independently associated with a
decreased risk of CIN. Our study demonstrated that prophylactic treatment with
high-dose atorvastatin reduced the risk of both SCr and CyC-based CIN and
suggested that CyC was a more reliable marker for early diagnosis of CIN compared
with SCr.
PMID- 29343075
TI - Tocilizumab in Giant Cell Arteritis: A Real-Life Retrospective Study.
AB - This study aims to evaluate (1) the efficacy and safety of tocilizumab (TCZ) as a
steroid-sparing agent in patients with giant cell arteritis (GCA) and (2) the
usefulness of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in
the follow-up and to detect disease activity. We retrospectively evaluated 12
patients with GCA treated with TCZ (8 mg/kg/mo). Pre- and posttherapy data about
clinical signs and symptoms, laboratory results, FDG-PET imaging study, and the
mean glucocorticoid (GC) dose were used to assess disease activity. Tocilizumab
achieved complete disease remission in all patients. Mean FDG-PET-detected
standard uptake value decreased from 2.05 +/- 0.64 to 1.78 +/- 0.45 ( P = .005).
In 2 patients in whom temporal arteries color Doppler sonography examination was
consistent with temporal arteritis, the hypoechoic halo disappeared after TCZ
treatment. Mean GC dose was tapered from 26.6 +/- 13.4 mg/d to 3.3 +/- 3.1 mg/d (
P < .0001). One-half of the patients discontinued GC therapy. Three patients
experienced severe adverse reactions and had to stop TCZ therapy. In accordance
with previous reports, TCZ is an effective steroid-sparing agent for GCA,
although careful monitoring of adverse drug reactions is needed. 18F
fluorodeoxyglucose positron emission tomography could be used to monitor disease
activity in TCZ-treated patients, but prospective studies are needed to confirm
these data.
PMID- 29343077
TI - Delayed Onset of Sleep in Adolescents With PAX6 Haploinsufficiency.
AB - OBJECTIVE: PAX6 haploinsufficiency ( +/-) can occur due to mutations involving
only PAX6 in patients with isolated aniridia or as contiguous gene deletions in
patients with Wilms tumor, aniridia, genitourinary anomalies, and range of
developmental and intellectual disabilities syndrome. Given the role of PAX6 in
pineal development and circadian regulation, adolescents with PAX6+/- may
experience sleep-wake disturbances. The purpose of this observational study was
to explore sleep-related phenotypes in adolescents with PAX6+/-. METHODS: This
study compared sleep phenotypes of nine subjects with PAX6+/- (aged 10-19 years)
with previously published data on healthy adolescents ( n = 25, aged 10-18
years). Subjects completed the Cleveland Adolescent Sleepiness Questionnaire
(CASQ), Patient Reported Outcomes Measurement Information System (PROMIS) Sleep
Disturbance (v. 1.0; 8a), and PROMIS Sleep-Related Impairment (v. 1.0; 8b)
Questionnaires and wore actigraphs for seven nights to record sleep patterns.
RESULTS: Total CASQ, PROMIS sleep-related impairment, and PROMIS sleep
disturbance scores were not statistically different between the groups ( ps >
.15). Actigraph data for lights off to sleep-onset time were found to be
significantly higher in subjects with PAX6+/- versus the healthy comparison group
(adjusted mean [95% confidence interval]: 20.1 min [8.1, 49.8] vs. 6.2 min [3.7,
10.4], respectively, p = .04). CONCLUSION: Both adolescents with PAX6+/- and the
healthy comparison group on average slept less than 8 hr/night, and overall sleep
deprivation in adolescents may have masked differences between groups. This study
used rare genetic disorders with biological vulnerability to sleep problems as a
genotype-phenotype model. Knowledge of sleep-related phenotypes will assist in
designing studies to manage sleep-related symptoms in adolescents.
PMID- 29343078
TI - Quality of life among HIV-infected individuals failing first-line antiretroviral
therapy in resource-limited settings.
AB - We evaluated health-related quality of life (QoL) in HIV infection participants
with virologic failure (VF) on first-line antiretroviral therapy (ART) in 9
resource-limited settings (RLS). ACTG SF-21 was completed by 512 participants at
A5273 study entry; 8 domains assessed: general health perceptions (GHP), physical
functioning (PF), role functioning (RF), social functioning (SF), cognitive
functioning (CF), pain (P), mental health (MH), and energy/fatigue (E/F); each
was scored between 0 (worst) to 100 (best). Mean QoL scores ranged from 67 (GHP)
to 91 (PF, SF, CF). QoL varied by country; high VL and low CD4 were associated
with worse QoL in most domains, except RF (VL only), SF (CD4 only) and CF
(neither). Number of comorbidities, BMI and history of AIDS were associated with
some domains. Relationships between QoL and VL varied among countries for all
domains. The association of worse disease status with worse QoL may reflect low
QoL when ART was initiated and/or deterioration associated with VF.
PMID- 29343079
TI - Cultural factors and oral health-related quality of life among dentate adults:
Hispanic community health study/study of Latinos.
AB - OBJECTIVE: Research on the relationships between acculturation, ethnic identity,
and oral health-related quality of life (OHRQOL) among the U.S. Hispanic/Latino
population is sparse. The aim of this study is to examine the association between
acculturation, ethnic identity, and OHRQOL among 13,172 adults in the 2008-2011
Hispanic Community Health Study/Study of Latinos (HCHS/SOL). DESIGN: Participants
self-reported their acculturation (immigrant generation, birthplace, residence in
the U.S., language, and social acculturation), ethnic identity (sense of
belonging and pride), and four OHRQOL measures. Key socio-demographic,
behavioral, and oral health outcomes were tested as potential confounders.
RESULTS: Overall, 57% of individuals experienced poor OHRQOL in at least one of
the domains examined. In multivariable analyses, some elements of higher
acculturation were associated with greater food restriction and difficulty doing
usual jobs/attending school, but not associated with pain or difficulty chewing,
tasting, or swallowing. While sense of belonging to one's ethnic group was not
associated with poor OHRQOL, low sense of pride was associated with food
restriction. Socio-behavioral characteristics were significant effect modifiers.
CONCLUSION: This study contributes to the understanding of the role of
Hispanic/Latino's cultural factors in OHRQOL perception and can inform targeted
strategies to improve OHRQOL in this diverse population.
PMID- 29343080
TI - Voices from Australia- concerns about HIV associated neurocognitive disorder.
AB - This study aimed to determine whether people living with HIV (PLHIV) are
concerned about HIV associated neurocognitive disorder (HAND) and would find
information and resources for HAND beneficial. An online survey focusing on the
experience of HAND was distributed via the website of Positive Life New South
Wales: a peak peer-support non-government organization in Australia. Of 126
respondents, 94 (74%) had heard of HAND, 52/94 (55%) had experienced concerns and
of these, 48/52 (92%) felt anxiety about discussing the subject. Of those who had
experienced concerns, 30/52 (58%) had spoken to someone about these concerns and
23/30 (77%) had received a positive response. Across the entire sample, 74 (59%)
had noticed symptoms of cognitive decline in themselves and/or others.
Respondents who noted a decrease in their ability to organize were on average
five years older than those who had not noticed a decline (p = 0.012, effect size
-.54). Forty-nine (39%) indicated that they would like guidance to initiate
discussion about HAND with their doctor, caregiver or other PLHIV. The survey
findings suggest that increasing awareness of HAND among PLHIV and their
caregivers, and providing resources to facilitate discussion about HAND may
assist to reduce concerns among PLHIV and enhance the effectiveness of clinical
review.
PMID- 29343081
TI - Atorvastatin Reduces Plasma Inflammatory and Oxidant Biomarkers in Patients With
Risk of Atherosclerotic Cardiovascular Disease.
AB - BACKGROUND: Oxidative stress and inflammation are associated with endothelial
injury and coronary artery disease. Inflammatory factors that promote oxidative
damage include endothelin-1 (ET-1), myeloperoxidase (MPO), and C-reactive protein
(CRP). Current guidelines recommend the use of statins in patients with risk of
atherosclerotic cardiovascular disease (ASCVD). AIM: To assess the impact of
atorvastatin on plasma inflammatory and oxidant biomarkers in patients with
moderate to very high risk of ASCVD. METHOD: Two hundred ten patients presented
to the cardiology clinic were included and stratified into low, moderate, high,
and very high risk of ASCVD. Moderate- (20 mg/d) to high-intensity (40 mg/d)
atorvastatin was prescribed. Plasma levels of lipids, ET-1, CRP, MPO, total
nitrite, lipid peroxides (thiobarbituric acid reactive substances [TBARS]), and
superoxide dismutase (SOD) activities were measured at baseline and 12 weeks
after treatment. RESULT: Relative to low-risk patients, baseline plasma
inflammatory markers of CRP, MPO, ET-1, and nitrite were higher in patients with
very high risk of ASCVD, whereas plasma SOD was lower (all P < .05). Use of high
and moderate atorvastatin therapy significantly reduced low-density lipoprotein
and total cholesterol levels, as well as plasma levels of CRP, MPO, nitrite, and
TBARS, and increased plasma SOD activity in patients with moderate to very high
risk of ASCVD, independent of lipid-lowering effects. CONCLUSIONS: Key markers of
oxidative stress/inflammation such as CRP, ET-1, total nitrite, and MPO are
associated with an increased risk of ASCVD. Moderate- and high-intensity
atorvastatin use reduces plasma oxidative stress and inflammation regardless of
ASCVD risk and independent of its lipid-lowering effect.
PMID- 29343082
TI - Systematic Review of the Effect of Adherence to Statin Treatment on Critical
Cardiovascular Events and Mortality in Primary Prevention.
AB - AIM: Analyze the relative risks of critical cardiovascular outcomes and mortality
associated with adherence to statin treatment in a clinical setting in people
with no history of prior cardiovascular disease (CVD). METHODS: A systematic
review of the literature was conducted up to December 2016. The outcomes of
interest were cardiovascular fatal or nonfatal events and all-cause mortality.
RESULTS: A total of 17 articles were included in a qualitative synthesis. Four
were case-control nested in a retrospective cohort design and the other 11 were a
cohort design. Seven studies compared the best adherer patients with the worst
adherers. In the 3 studies (317 603 participants) that considered ischemic heart
disease in this group, the pooled reduction in risk was 18% (95% confidence
interval [CI]: 14%-22%, I2 = 0%); for the CVD outcome, 2 studies (131 477
participants) showed a pooled reduction in risk of 47% (95% CI: 36%-56%, I2 =
84.7%) with 1 included study showing a much larger reduction than the others; for
the cerebrovascular event (CeVD) outcome, 2 studies (155 726 participants) showed
a pooled reduction in risk of 26% (95% CI: 18%-34%, I2 = 0%); and for mortality,
the reduction in risk was 49% (95% CI: 39%-57%, I2 = 62.4%). The other 4 studies
(147 859 participants) compared the most adherent group with the rest. These
showed a pooled risk reduction of CVD of 22% (95% CI: 6%-27%, I2 = 0).
CONCLUSION: Adherence to statins treatment is shown as a key element for primary
prevention, although these are observational data and the risk of bias from
confounding cannot be ruled out. Standardization of measures of adherence to
treatment would improve comparability between studies. Further research is
warranted to design effective interventions to improve patients' adherence.
PMID- 29343083
TI - Polarized macrophage subsets differentially express the drug efflux transporters
MRP1 and BCRP, resulting in altered HIV production.
AB - Introduction Macrophages play an important role in HIV, where they are a cellular
reservoir. Macrophages are polarized into two phenotypes: pro-inflammatory M1
macrophages and anti-inflammatory M2 macrophages, which may have altered
expression of drug efflux transporters, including BCRP and MRP1. These
differences may result in subtherapeutic concentrations of antiretrovirals inside
of macrophages and viral replication. Methods U937 and U1 cells were polarized to
the M1 or M2 phenotype via IFN-gamma and LPS, or IL-4, IL-13, and LPS.
Transporter expression was assessed via PCR and Western blotting, and transporter
function was assessed via fluorescent dye assays. Transporter function was
blocked with the inhibitors MK571 or KO143. Protein expression was confirmed in
monocyte-derived macrophages. p24 production was assessed in U1 cells via enzyme
linked immunosorbent assay. Results mRNA and protein analysis demonstrated higher
expression of MRP1 in M1 macrophages, while BCRP expression was downregulated in
M1 macrophages. Treatment with inhibitors of transporter function decreased the
difference in intracellular fluorescence between polarized macrophages.
Differences in protein expression, which were observed with U937 cells, were
confirmed in monocyte-derived macrophages. M1, but not M2 cells treated with
MK571, showed decreased p24 production, consistent with reported MRP1 transporter
expression. Conclusions These results support our hypothesis that there is
differential expression of MRP1 and BCRP on M1 and M2 polarized macrophages and
suggests that these differences may result in altered intracellular
concentrations of antiretrovirals in macrophages and alter viral production in
these cells. Targeting these differences may be a strategy to decrease viral
replication in HIV-infected individuals.
PMID- 29343084
TI - The correlation analysis of miRNAs and target genes in metastasis of cervical
squamous cell carcinoma.
AB - AIM: This study was intended to identify the metastasis-related miRNAs and target
genes in cervical squamous cell carcinoma. MATERIALS & METHODS: The mRNA and
miRNA next-generation sequencing data were downloaded. Differential expression
analysis was carried out, followed by target gene prediction of differentially
expressed miRNAs. The biological function of differentially expressed genes was
performed. Validation was carried out by survival analysis and qRT-PCR. RESULTS:
N4BP3 were associated with the survival time of patients. Hsa-mir-451 and hsa-mir
486 were related to tumor differentiation stage. Validated expression of hsa-mir
24-2, hsa-mir-582, NOTCH1, PIP4K2B, DIP2B and IGFBP5 was consistent with the
bioinformatics analysis. CONCLUSION: Alterations of miRNAs and target genes may
be useful in understanding the metastasis mechanisms of cervical squamous cell
carcinoma.
PMID- 29343085
TI - A Lack of Systemic Absorption Following the Repeated Application of Topical
Quetiapine in Healthy Adults.
AB - In the absence of suitable oral or intravenous access for medication
administration and when the intramuscular medications are undesirable,
alternative routes for drug delivery may be considered. Antipsychotics
administered via an inhaled, intranasal, rectal, or topical route have been
described in the literature. Topically administered antipsychotics have been
previously reported to produce negligible systemic absorption despite being used
in clinical practice for nausea and behavioral symptoms associated with dementia.
Additionally, the American Academy of Hospice and Palliative Medicine recommends
against the use of topical medications that lack supporting literature. Three
studies have assessed the systemic absorption of different antipsychotics after
administration of only a single, topically applied dose. To evaluate whether the
repeated administration of a topically applied antipsychotic may result in
detectable serum levels in an accumulating fashion, a pharmacokinetic study was
conducted. Five healthy, adult participants consented to receive extemporaneously
prepared topical quetiapine in Lipoderm every 4 hours for a total of 5 doses.
Blood samples were drawn at baseline and hours 2, 4, 8, 12, 16, and 24, and serum
quetiapine concentrations were measured using high-performance liquid
chromatography. Quetiapine was undetectable in every sample from 3 participants.
Two participants had minimally detectable serum quetiapine levels no sooner than
hour 12 of the study period. Extemporaneously prepared quetiapine in Lipoderm
resulted in nonexistent or minimal serum level following repeated topical
administration. The use of topically applied quetiapine should still be
questioned.
PMID- 29343086
TI - Percutaneous Nephrolithotomy and Spina Bifida: Complex Major Stone Surgery?
AB - BACKGROUND: The incidence of spina bifida (SB) is ~1:1000, and risk of stone
disease is substantially raised in SB. This is the unique published study of the
outcome of patients with SB undergoing percutaneous nephrolithotomy (PCNL)
compared to a neurologically intact historically matched control group at the
same institution. PATIENTS AND METHOD: A series of 96 PCNLs in 13 SB and 50 non
SB patients was analyzed. The following measurements were recorded: (1)
Comorbidities; (2) Preoperative: (renal function, American Society of
Anesthesiologists [ASA] score); (3) Intraoperative: (anesthesia time, number of
tracks, stone-free rate); and (4) Postoperative: (sepsis, intensive therapy unit
and total length of stay, transfusion rate, stone composition, rate of stone
disease-related nephrectomy). RESULTS: Retrograde access to the ureter was
impossible in all cases of SB. The median ASA grade (OR 10.5, 95% confidence
interval [CI] 2.6-42.7) and operative time (median difference 30 minutes, 95% CI
20-40) were both higher in the SB cohort. Surgeon's estimate of stone-free rate
was significantly lower in the SB cohort (46% vs 82%). Intensive care requirement
(0.29 days/PCNL vs 0.1 days/PCNL); total hospital stay (7 days vs 4 days);
postoperative transfusion rate (11.8% vs 1.6%); and sepsis rate (38% vs 1.6%)
were all significantly higher in the SB group. Repeat PCNL and nephrectomy for
recurrent stone disease were both significantly increased in SB cohort compared
to control group. CONCLUSIONS: PCNL in patients with SB is associated with
multiple parameters of poor outcome. Patients with SB should be counseled about
increased peri-operative risk and likelihood of stone recurrence. In an era where
hospitals are judged according to comparative outcomes, a case may be made for
comparing PCNL in this cohort of patients separately because of the significantly
increased peri- and postoperative morbidity.
PMID- 29343087
TI - Sulfhydrated Sirtuin-1 Increasing Its Deacetylation Activity Is an Essential
Epigenetics Mechanism of Anti-Atherogenesis by Hydrogen Sulfide.
AB - AIMS: Hydrogen sulfide (H2S) has a protective role in the pathogenesis of
atherosclerosis by multiple pathways. Sirtuin-1 (SIRT1) is a histone deacetylase,
as an essential mediated longevity gene, and has an anti-atherogenic effect by
regulating the acetylation of some functional proteins. Whether SIRT1 is involved
in protecting H2S in atherosclerosis and its mechanism remains unclear. RESULTS:
In ApoE-knockout atherosclerosis mice, treatment with an H2S donor (NaHS or
GYY4137) reduced atherosclerotic plaque area, macrophage infiltration, aortic
inflammation, and plasma lipid level. H2S treatment increased aorta and liver
SIRT1 mRNA expression. Overexpression or slicing cystathionine gamma lyase (CSE)
also changed intracellular SIRT1 expression. CSE/H2S treatment increased SIRT1
deacetylation in endothelium and hepatocytes and macrophages, then induced
deacetylation of its target proteins (P53, P65, and sterol response element
binding protein), thereby reducing endothelial and macrophage inflammation and
inhibiting macrophage cholesterol uptake and cholesterol de novo synthesis of
liver. Also, CSE/H2S induced SIRT1 sulfhydration at its two zinc finger domains,
increased its zinc ion binding activity to stabilize the alpha-helix structure,
lowered its ubiquitination, and reduced its degradation. INNOVATION: H2S is a
novel SIRT1 activator by direct sulfhydration. Because SIRT1 has a role in
longevity, H2S may be a protector for aging-related diseases. CONCLUSION:
Endogenous CSE/H2S directly sulfhydrated SIRT1, enhanced SIRT1 binding to zinc
ion, then promoted its deacetylation activity, and increased SIRT1 stability,
thus reducing atherosclerotic plaque formation. Antioxid. Redox Signal. 00, 000
000.
PMID- 29343088
TI - Creating and testing regulatory focus messages to enhance medication adherence.
AB - Objectives Strategies were explored to improve patient adherence to
cardioprotective medications by borrowing from a motivational framework used in
psychology, regulatory focus theory. The current study is part of a larger
randomized control trial and was aimed at understanding what written educational
messages, based on patients' regulatory focus tendency, resonated with each
individual as a potential reminder to take medications. This study was also aimed
at understanding why messages resonated with the patients. Methods Twenty
veterans were tested for regulatory fitand presented with messages dependent on
focus tendency. In-person semi-structured interviews were conducted to collect
feedback of messages. An iterative analysis drawing primarily on matrix and
reflexive team analyses was conducted. Result Six promotion and six prevention
messages emerged, such as "team up with your provider to create a combination of
medications to prevent illness" and "Live your best life - Take your
medications". Five themes related to types of health messages that spoke to
patients' regulatory fit were discovered: relatability; empowerment and control;
philosophy on life; relationship with provider and medications; and vocabulary
effect on the impact of messages. Discussion Motivational messages based on
regulatory fit may be useful in improving patient medication adherence, leading
to improved cardiovascular outcomes.
PMID- 29343089
TI - Peer characteristics associated with improved glycemic control in a randomized
controlled trial of a reciprocal peer support program for diabetes.
AB - Objective In a secondary analysis of a randomized controlled trial of diabetes
reciprocal peer support, we examined characteristics of peers associated with
improvements in their partner's glycemic control. Methods A total of 102 adults
with diabetes were randomized to the reciprocal peer support arm (vs. a nurse
care management arm). The primary outcome was change in A1c over six months.
Intermediate outcomes were insulin initiation and peer engagement. A number of
baseline characteristics of peers were hypothesized to influence outcomes for
their peer, and concordant characteristics of peer dyads were hypothesized that
would influence outcomes for both peer partners. Results Improvement in A1c was
associated with having a peer older than oneself ( P < .05) or with higher
diabetes-related distress ( P < .01). Participants with peers who reported poorer
health at baseline had worse glycemic control at follow-up ( P < .01).
Hypothesized concordant characteristics were not associated with A1c
improvements. Participants whose peers had a more controlled self-regulation
style were more likely to initiate insulin ( P < .05). Discussion The improved
outcomes of peers whose partners were older and reported more diabetes distress
at baseline supports the need for further research into the peer characteristics
that lead to improved outcomes. This could allow for better matching and more
effective partnerships.
PMID- 29343090
TI - Identifying COPD patients at risk for worse symptoms, HRQoL, and self-efficacy: A
cluster analysis.
AB - Objectives To identify clusters of chronic obstructive pulmonary disease (COPD)
patients with distinct beliefs about their illness in terms of symptoms, health
related quality of life (HRQoL), self-efficacy, and daily life physical activity
(DLPA). Methods This cross-sectional study included 150 COPD outpatients. The
patients' illness perceptions, clinical control, HRQoL, self-efficacy, and DLPA
(accelerometry) were evaluated. A cluster analysis was conducted using data from
the Illness Perceptions Questionnaire - Revised to establish groups of patients
with distinct illness perceptions. Differences between clusters were tested using
a T-test or a Mann-Whitney U test. Results The cluster analysis revealed two
groups: distressed ( n = 95) and coping ( n = 55). Despite the fact that both
clusters presented similar pulmonary function, between-cluster differences were
observed in their self-efficacy, dyspnea, HRQoL, clinical control ( p < 0.001),
and educational level ( p = 0.002). The levels of DLPA did not differ between the
clusters. Discussion We observed that clinically stable COPD patients who
displayed higher emotional representations and less coherence had heightened
symptoms, poorer HRQoL, worse self-efficacy, and lower educational levels. These
results emphasize the need to routinely evaluate illness perceptions in COPD
patients to target and tailor the proper treatment to improve these important
health outcomes.
PMID- 29343091
TI - Terminalia chebula supplementation attenuates cisplatin-induced nephrotoxicity in
Wistar rats through modulation of apoptotic pathway.
AB - In the present study, we have evaluated the nephroprotective effect of
hydroalcoholic extract of Terminalia chebula in cisplatin-induced nephrotoxicity
model. Standardised extract was orally administered to Wistar rats for 10 days at
different doses. On day 7, 8 mg/kg of cisplatin was administered intra
peritoneally to rats in all groups. T. chebula, in a dose-dependent manner
significantly inhibited the elevation of serum creatinine, blood urea nitrogen
and oxidant stress markers. The immunohistochemical analysis revealed the
increased levels of apoptotic markers and cytokines in cisplatin group were
significantly lowered by T. chebula extract. The cisplatin-treated rats kidney
showed diffused tubular necrosis and infilteration of inflammatory cells which
was reversed in the treatment group. Chemical characterisation of extract by HPLC
revealed the presence of corilagin, chebulinic, chebulagic, chebulic, gallic and
ellagic acid. The findings of this study discovered that T. chebula ameliorated
oxidative and histological damage caused by cisplatin.
PMID- 29343092
TI - Health Information at a Global Level: Working to Support the Information Paradox
Countries.
PMID- 29343093
TI - Nosology Work: One Step beyond the Medical Record Department.
AB - This article discusses the role of the nosologist/health information management
(HIM) professional in a venue one step beyond the hospital's medical record
department. It provides a glimpse of the role of the HIM professional at a
statistical government agency, the National Center for Health Statistics (NCHS)
in the United States, and focuses primarily on the collaborative work that is
performed by the HIM professional at NCHS. The challenges presented in survey
coding will be discussed, while practical examples of how we have chosen to
improve the data collection, data processing and data reporting processes will
also be addressed.
PMID- 29343094
TI - Improving Health Records in Developing Countries: The Suriname Experience.
PMID- 29343095
TI - Health Information Management Practice in Sri Lanka.
AB - Health information system development in Sri Lanka has generally been a low
priority. Weaknesses exist in many areas, including vital registration, and
hospital information such as inpatient and outpatient morbidity and mortality
data. Lapses in hospital information systems are mainly due to incomplete patient
medical records; non-availability, inaccuracy and illegibility of the final
diagnoses on the front sheets; shortage of trained statistical staff; lack of
supervision at all levels; and lack of facilities at medical record departments.
WHO's South-East Asian Regional Organization, in collaboration with the
Australian National Centre in Classification in Health, has developed a group of
trainers who conduct MR/HIM and ICD-10 training courses within the country.
PMID- 29343097
TI - Electronic Health Information Management: The Future is Ours to Embrace.
PMID- 29343096
TI - Estonia's Health Information System and the Digital Health Record.
PMID- 29343098
TI - Health Information Management Education Programs in Germany.
PMID- 29343099
TI - Modelling the water-plant cuticular polymer matrix membrane partitioning of
diverse chemicals in multiple plant species using the support vector machine
based QSAR approach.
AB - In this study, a support vector machine (SVM) based multi-species QSAR
(quantitative structure-activity relationship) model was developed for predicting
the water-plant cuticular polymer matrix membrane (MX) partition coefficient,
KMXw of diverse chemicals using two simple molecular descriptors derived from the
chemical structures and following the OECD guidelines. Accordingly, the
Lycopersicon esculentum Mill. data were used to construct the QSAR model that was
externally validated using three other plant species data. The diversity in
chemical structures and end-points were verified using the Tanimoto similarity
index and Kruskal-Wallis statistics. The predictive power of the developed QSAR
model was tested through rigorous validation, deriving a wide series of
statistical checks. The MLOGP was the most influential descriptor identified by
the model. The model yielded a correlation (r2) of 0.966 and 0.965 in the
training and test data arrays. The developed QSAR model also performed well in
another three plant species (r2 > 0.955). The results suggest the appropriateness
of the developed model to reliably predict the plant chemical interactions in
multiple plant species and it can be a useful tool in screening the new chemical
for environmental risk assessment.
PMID- 29343100
TI - The Effect of an Orthopedic Hand Surgeon's Attire on Patient Confidence and
Trust.
AB - BACKGROUND: Multiple studies have concluded that patients are more likely to
understand and trust physicians who dress in more formal attire (shirt and tie)
as opposed to casual attire (t-shirts and jeans). The white coat has repeatedly
been reported as a major source of trust and confidence in a patient's eyes.
METHODS: This study explores the effect an orthopedic hand surgeon's attire has
on a patient's perception of their surgeon's clinical values. All patients 18
years of age and older who visited our orthopedic hand surgeon's suburban
outpatient practice were asked to participate in our survey-based study. RESULTS:
Ninety-seven surveys were completed and included. A majority of our responders
are female (n = 59, 60.8%), Caucasian (n = 83, 85.6%) between the ages of 55 and
74 years (n = 40, 41.2%), currently employed (n = 59, 60.8%) with private health
insurance (n = 69, 71.1%), and married (n = 64, 66.0%). Patients rated male and
female hand surgeons wearing a white coat highest using the Likert scale and when
asked about their perceived clinical qualities. Patients consistently poorly
rated their surgeons wearing casual attire. Patients did note that the white
coat, or any specific attire, was not necessary during the initial encounter to
build a strong patient-surgeon relationship. Finally, goatees and beards do not
positively or negatively impact a surgeon's patient-constructed image.
CONCLUSIONS: Combining strong clinical skills with appropriate clinical attire
highlighted by the physician wearing a white coat appears to be an effective way
to enhance patient satisfaction while ultimately gaining the trust and respect
needed to properly care for patients.
PMID- 29343102
TI - The Development of the Philippine Medical Records Association Inc.
PMID- 29343103
TI - M-Health - Providing Excellence in Quality of Care through Wireless, Telehealth
and Mobile Technology Integration: Report on the IQPC Conference, Sydney, 30-31
March 2004.
PMID- 29343101
TI - MACON: a web tool for computing DNA methylation data obtained by the Illumina
Infinium Human DNA methylation BeadArray.
AB - AIM: Bioinformatics analysis for Illumina Infinium Human DNA methylation
BeadArray is essential, but still remains difficult task for many experimental
researchers. We here aimed to develop a browser-accessible bioinformatics tool
for analyzing the BeadArray data. MATERIALS & METHODS: The tool was established
as an analytical pipeline using R, Perl and Python programming languages.
RESULTS: We introduced a method that groups neighboring probes into a genomic
block, which facilitated efficient identification of densely
methylated/unmethylated regions. The tool, MACON, provided probe filtering, beta
mixture quantile normalization, grouping into genomic blocks, annotation and
production of a data subset. CONCLUSION: MACON allows researchers to analyze the
BeadArray data using a web browser ( http://epigenome.ncc.go.jp/macon ).
PMID- 29343104
TI - What Do other Organisations Do about Continuing Professional Development?
PMID- 29343105
TI - The Health IT Rollout: Supporting the End Users.
PMID- 29343106
TI - Quality of Final Diagnosis Coding in the Medical Records of Selected Hospitals in
the Colombo District, Sri Lanka.
AB - Clinical coding is a method of translating a clinical description of a disease or
procedure into a standard code. Sri Lanka adopted the system of coding
recommended by the WHO, The International Classification of Diseases - 10th
Revision (ICD-10), in 1997, and this study was undertaken with the objectives of
assessing the quality of ICD coding and to identify some factors influencing
coding quality in this country. A sample of 1091 medical records was selected
from six hospitals in the Colombo District, representing all categories of
hospitals in the area. Quality of coding was assessed by using the Australian
Coding Benchmark Audit (ACBA), a coding quality assessment tool developed by the
National Centre for Classification in Health, Australia. It was found that the
availability of the final diagnosis on front sheets of medical records was
satisfactory (94.7%), but the accuracy of the diagnostic statement was
unsatisfactory (54%). Out of the six hospitals studied, only the Teaching
Hospital and the Peripheral Unit practiced coding. The overall rate of accuracy
of ICD coding in the Colombo District hospitals was 31%, which is unsatisfactory.
It is recommended that training opportunities in ICD-10 and other related
subjects should be made available to the coders. Efforts should be made to
improve the familiarity of the Medical Officers with the WHO guidelines on
recording diagnostic information for ICD coding.
PMID- 29343107
TI - Clinical Coders and Decision Making.
AB - Clinical coders operate at six identifiable levels, which can be described as
beginner, trainee coder, entry, competent, accredited and advanced levels. In
this article these levels are elaborated within the theoretical perspectives of
Simon's four-stage and Wilson and Walsh's six-stage models of systematic decision
making. The article then examines briefly the importance of understanding how
clinical coders make decisions, because of both the coder's crucial role in
determining hospital funding, and the reliance of research upon access to
accurate data. Finally, future avenues for study in this area are suggested.
PMID- 29343108
TI - Health Information Management: An International Focus.
PMID- 29343109
TI - Preparing for the New Information Environment.
PMID- 29343110
TI - Can the physical environment itself influence neurological patient activity?
AB - PURPOSE: To evaluate if a changed physical environment following redesign of a
hospital ward influenced neurological patient physical and social activity.
METHODS: A "before and after" observational design was used that included 17
acute neurological patients pre-move (median age 77 (IQR 69-85) years Ward A and
20 post-move (median age 70 (IQR 57-81) years Ward B. Observations occurred for 1
day from 08.00-17.00 using Behavioral Mapping of patient physical and social
activity, and location of that activity. Staff and ward policies remained
unchanged throughout. An Environmental Description Checklist of each ward was
also completed. RESULTS: Behavioral Mapping was conducted pre-/post-move with a
total of 801 Ward A and 918 Ward B observations. Environmental Description
Checklists showed similarities in design features in both neurological wards with
similar numbers of de-centralized nursing stations, however there were more
single rooms and varied locations to congregate in Ward B (30% more single
patient rooms and separate allied health therapy room). Patients were alone >60%
of time in both wards, although there was more in bed social activity in Ward A
and more out of bed social activity in Ward B. There were low amounts of physical
activity outside of patient rooms in both wards. Significantly more physical
activity occurred in Ward B patient rooms (median = 47%, IQR 14-74%) compared to
Ward A (median = 2% IQR 0-14%), Wilcoxon Rank Sum test z = -3.28, p = 0.001.
CONCLUSIONS: Overall, patient social and physical activity was low, with little
to no use of communal spaces. However we found more physical activity in patient
rooms in the Ward B environment. Given the potential for patient activity to
drive brain reorganization and repair, the physical environment should be
considered an active factor in neurological rehabilitation and recovery.
Implications for Rehabilitation Clinicians should include consideration of the
impact of physical environment on physical and social activity of neurological
patients when designing therapeutic rehabilitation environments. Despite
architectural design intentions patient and social activity opportunities can be
limited. Optimal neurological patient neuroplasticity and recovery requires
sufficient environmental challenge, however current hospital environments for
rehabilitation do not provide this.
PMID- 29343111
TI - Getting the Most from Routinely Collected Data.
PMID- 29343112
TI - Eight Methods for Improving Coding Quality and Efficiency.
PMID- 29343113
TI - Ninth National Centre for Classification in Health Conference. 16-18 March 2005.
Perth, Western Australia.
PMID- 29343114
TI - Governance and Our Organisation.
PMID- 29343115
TI - Health Informatics and Health Professionals.
PMID- 29343116
TI - Challenges in Coding and Classification.
PMID- 29343117
TI - 25th National Conference, Health Information Management Association of Australia.
Geelong, July 2005. Conference Discharge Summary.
PMID- 29343118
TI - Coding Rules! Ninth National Centre for Classification in Health Conference. 16
18 March 2005. Perth, Western Australia.
PMID- 29343119
TI - Electronic Health Records: Security, Safety and Archiving.
PMID- 29343120
TI - An update on the advancing high-throughput screening techniques for patch clamp
based ion channel screens: implications for drug discovery.
AB - INTRODUCTION: Automated patch clamp (APC) devices have become commonplace in many
industrial and academic labs. Their ease-of-use and flexibility have ensured that
users can perform routine screening experiments and complex kinetic experiments
on the same device without the need for months of training and experience. APC
devices are being developed to increase throughput and flexibility. Areas
covered: Experimental options such as temperature control, internal solution
exchange and current clamp have been available on some APC devices for some time,
and are being introduced on other devices. A comprehensive review of the
literature pertaining to these features for the Patchliner, QPatch and Qube and
data for these features for the SyncroPatch 384/768PE, is given. In addition,
novel features such as dynamic clamp on the Patchliner and light stimulation of
action potentials using channelrhodosin-2 is discussed. Expert opinion: APC
devices will continue to play an important role in drug discovery. The
instruments will be continually developed to meet the needs of HTS laboratories
and for basic research. The use of stem cells and recordings in current clamp
mode will increase, as will the development of complex add-ons such as dynamic
clamp and optical stimulation on high throughput devices.
PMID- 29343121
TI - Health Data Standards Committee Meeting Report.
PMID- 29343122
TI - Use of the Godin leisure-time exercise questionnaire in multiple sclerosis
research: a comprehensive narrative review.
AB - PURPOSE: The Godin Leisure-Time Exercise Questionnaire has been a commonly
applied measure of physical activity in research among persons with multiple
sclerosis over the past decade. This paper provides a comprehensive description
of its application and inclusion in research on physical activity in multiple
sclerosis. METHOD: This comprehensive, narrative review included papers that were
published between 1985 and 2017, written in English, involved participants with
multiple sclerosis as a primary population, measured physical activity, and cited
one of the two original Godin papers. RESULTS AND CONCLUSION: There is a broad
scope of research that has included the Godin Leisure-Time Exercise Questionnaire
in persons with multiple sclerosis. Overall, 8 papers evaluated its psychometric
properties, 21 evaluated patterns of physical activity, 24 evaluated correlates
or determinants of physical activity, 28 evaluated outcomes or consequences of
physical activity, and 15 evaluated physical activity interventions. The Godin
Leisure-Time Exercise Questionnaire is a valid self-report measure of physical
activity in persons with multiple sclerosis, and further is an appropriate,
simple, and effective tool for describing patterns of physical activity,
examining correlates and outcomes of physical activity, and provides a sensitive
outcome for measuring change in physical activity after an intervention.
Implications for rehabilitation There is increasing interest in physical activity
and its benefits in multiple sclerosis. The study of physical activity requires
appropriate and standardized measures. The Godin Leisure-Time Exercise
Questionnaire is a common self-report measure of physical activity for persons
with multiple sclerosis. Godin Leisure-Time Exercise Questionnaire scores are
reliable measures of physical activity in persons with multiple sclerosis. The
Godin Leisure-Time Exercise Questionnaire further is an appropriate, simple, and
effective tool for describing patterns of physical activity, examining correlates
and outcomes of physical activity participation, and is an advantageous primary
outcome for measuring change in physical activity in response to an intervention.
PMID- 29343124
TI - Health Information Management in Epidemiological Research.
PMID- 29343123
TI - Ninth National Centre for Classification in Health Conference. 16-18 March 2005.
Perth, Western Australia.
PMID- 29343125
TI - The changing pattern and determinants of declining consanguinity in Jordan during
1990-2012.
AB - BACKGROUND: Consanguinity is a deep rooted cultural trait in Jordan. AIM: To
examine the patterns and determinants of declining rates of consanguineous
marriage in Jordan during 1990-2012 in the context of the changing pattern of
socio-economic and demographic conditions. MATERIALS AND METHODS: The data come
from the 1990 and 2012 Jordan Population and Family Health Surveys (JPFHSs). A
total of 6461 women in 1990 and 11,352 women in 2012 were successfully
interviewed. Descriptive and multivariate statistical techniques were used for
data analysis. RESULTS: Consanguinity was found to be widely practiced (35% in
2012) until recent times in Jordan. However, there has been a secular declining
trend over the last few decades as the practice of consanguinity has declined
from 56% in 1990 to 35% in 2012. Increasing age at marriage and female education,
higher level of education of husbands, declining family size, increasing rate of
urbanisation and female employment, exposure to mass media and higher economic
status appeared as significant predictors of declining consanguinity in Jordan.
CONCLUSIONS: The findings of this study support Goode's hypothesis of a decrease
of consanguinity with modernisation. Although consanguinity is a deeply rooted
cultural trend in Jordan, it is gradually losing ground due to modernisation and
socio-demographic transition of the country.
PMID- 29343126
TI - Challenges in Coding and Classification.
PMID- 29343128
TI - Efficacy and safety of flexibly dosed brexpiprazole for the adjunctive treatment
of major depressive disorder: a randomized, active-referenced, placebo-controlled
study.
AB - OBJECTIVE: To assess the efficacy, safety, and tolerability of brexpiprazole as
adjunctive treatment in adults with major depressive disorder (MDD) and an
inadequate response to prior antidepressant treatment (ADT). METHODS: Patients
with a current major depressive episode after prior treatment with 1-3 ADTs
entered an 8- or 10-week prospective treatment phase in which they received
double-blind placebo adjunct to open-label ADT. Inadequate responders were
randomized (2:2:1) to brexpiprazole 2-3 mg/day, placebo, or quetiapine extended
release (XR) 150-300 mg/day, adjunct to the same ADT, for 6 weeks. The primary
efficacy endpoint was the change from baseline (randomization) to week 6 in
Montgomery-Asberg Depression Rating Scale (MADRS) total score. The key secondary
efficacy endpoint was the change in Sheehan Disability Scale (SDS) mean score.
RESULTS: Adjunctive brexpiprazole showed a greater improvement in MADRS total
score than adjunctive placebo (least squares mean difference [95% confidence
interval] = -1.48 [-2.56, -0.39]; p = .0078), whereas adjunctive quetiapine XR
did not separate from placebo (-0.30 [-1.63, 1.04]; p = .66). Adjunctive
brexpiprazole failed to separate from placebo on the SDS mean score (-0.23 [
0.52, 0.07]; p = .13), but did improve functioning on two of the three SDS items
(family life and social life). The most frequent treatment-emergent adverse
events in patients receiving brexpiprazole were akathisia (6.1%), somnolence
(5.6%), and headache (5.6%). CONCLUSIONS: Adjunctive brexpiprazole 2-3 mg/day
improved symptoms of depression compared with adjunctive placebo in patients with
MDD and an inadequate response to ADTs, and was well tolerated with no unexpected
side effects.
PMID- 29343129
TI - Major Achievement by Associate Professor Johanna Westbrook: Election to the
American College of Medical Informatics as an International Fellow.
AB - Congratulations to Associate Professor Johanna Westbrook PhD, MHA, GradDipAppEpi,
BAppSc (Medical Record Administration), who has been elected to the American
College of Medical Informatics as an International Fellow. The Fellowship is the
highest recognition possible in the health informatics discipline. Based upon
peer election from current College Fellows, no more than two Fellowships are
offered in any one year, and there are currently only two other Australian
Fellows. This is a wonderful honour as it marks the highest peer recognition
possible from the international community, reflecting Johanna's outstanding
research work. Johanna is currently Deputy Director of the Centre for Health
Informatics at the University of New South Wales and is an honorary Associate
Professor at the School of Health Information Management at the University of
Sydney. Johanna has published over 80 refereed journal articles and has received
numerous research grants, the most recent of which is a National Health and
Medical Research Council Project Grant of $583 000 for a study investigating the
safety and effectiveness of hospital e-prescribing systems.
PMID- 29343130
TI - A community-based exercise program to increase participation in physical
activities among youth with disability: a feasibility study.
AB - PURPOSE: To evaluate the feasibility of a student-mentored community-based
exercise program for youth with disability. METHOD: Nineteen youth (nine female;
mean age 18 years) with disability (seven cerebral palsy, six Down syndrome,
three spina bifida, two autism spectrum disorder, one spinal cord injury) were
recruited. Each participant was matched with a student mentor and exercised twice
a week for 12 weeks at their local gymnasium. Five domains of feasibility were
assessed: demand, implementation, practicality, limited efficacy testing, and
acceptability. RESULTS: Demand comprised 55 expressions of interest.
Demonstrating evidence of implementation, 91% of scheduled sessions were attended
and training fidelity (comparing training load in weeks 1 and 12) showed exercise
intensity significantly increased for strength and aerobic exercises. The program
was practical with no major and 17 minor adverse events (e.g., muscle soreness).
Limited efficacy testing was demonstrated by increased arm (4 kg, 95% CI: 1-7)
and leg strength (43 kg, 95% CI: 24-62), walking endurance (80 m, 95% CI: 24
137), and improvement in three dimensions of health-related quality of life
(autonomy, physical, and psychological well-being). The program was accepted very
positively by participants. CONCLUSIONS: A student-mentored community-based
exercise program feasibly engages youth with disability in community-based
exercise. Implications for Rehabilitation A 12-week community-based student
mentored exercise program for youth with disability is feasible. Exercising in a
real-world setting with a student mentor has a positive effect on physical and
psychological well-being of youth with disability.
PMID- 29343131
TI - Safety and tolerability of plecanatide in patients with chronic idiopathic
constipation: long-term evidence from an open-label study.
AB - OBJECTIVE: This multi-center, fixed-dose, open-label study evaluated the long
term safety and tolerability of once-daily oral plecanatide for the treatment of
adults with chronic idiopathic constipation (CIC). METHODS: Eligible patients
completed a phase 2b or phase 3 double-blind study of plecanatide, or had not
previously been treated with plecanatide. Enrolled patients received plecanatide
(3 or 6 mg) for up to 72 weeks. Safety and tolerability were assessed by the
incidence, nature, and severity of spontaneously reported treatment-emergent
adverse events (TEAEs). Patients also completed Patient Global Assessment
questionnaires, which included measures of treatment satisfaction and the desire
to continue treatment. RESULTS: There were 2370 patient exposures in this study,
with the vast majority (90.5%) receiving treatment with plecanatide 6 mg. At the
time of study closure, 1932 (81.5%) had completed or were still receiving study
drug. TEAEs were qualitatively and quantitatively similar to those observed in
prior double-blind studies. The most common TEAEs were diarrhea (7.1%) and
urinary tract infection (2.2%). TEAEs leading to discontinuation occurred in 5.3%
of patients, with diarrhea leading to discontinuation in 3.1%. Most TEAEs were
mild/moderate in severity and were generally considered not related to
plecanatide treatment. At the end of treatment, the median score for treatment
satisfaction was 4.0 (quite satisfied), and the median score for treatment
continuation was 4.0 (quite likely). CONCLUSIONS: Long-term treatment of adults
with CIC demonstrated that plecanatide was safe and well tolerated, with low TEAE
and discontinuation rates. Patients indicated satisfaction and a desire to
continue with plecanatide treatment.
PMID- 29343132
TI - IT14/2 Semantic Interoperability Meeting Report 20 February 2006.
PMID- 29343133
TI - Central nervous system malformation associated with methamphetamine abuse during
pregnancy.
AB - INTRODUCTION: Prenatal methamphetamine exposure is related to prematurity, fetal
growth restriction, neurobehavioral effects and long-term motor and cognitive
sequelae. PATIENT PRESENTATION: We report the case of a newborn from a Filipina
with no prenatal care with a complex brain malformation. Methamphetamine was
identified in maternal and neonatal urine and in maternal hair, raising our
suspicion of methamphetamine as a cause of this malformation. DISCUSSION:
Methamphetamine abuse is a growing problem worldwide. There are little data on
its effect on the fetus. To our knowledge, no fetal brain abnormalities have been
associated with its use. In our case, the lack of antenatal control does not
allow us to date when this malformation appeared. CONCLUSION: The aim of our
report is to generate awareness of the possible association between
methamphetamine abuse during pregnancy and central nervous system malformations.
PMID- 29343134
TI - Implementation of vaginal cleansing prior to cesarean delivery to decrease
endometritis rates.
AB - BACKGROUND: Endometritis is a postpartum complication that is more common after
cesarean delivery. It frequently requires intravenous antibiotic administration,
prolonged hospital stays, and carries a risk of sepsis or abscess formation.
Precesarean vaginal preparation has been shown to decrease the risk of
endometritis in patients who have labored or have ruptured membranes. OBJECTIVE:
The objective of this study was to assess the practical implementation of a
protocol for vaginal cleansing prior to cesarean delivery and the subsequent
effect on endometritis rates in a clinical setting. STUDY DESIGN: This is a
before-after retrospective cohort study evaluating the first 6 months of
implementation of a vaginal cleansing protocol at a single institution. The
primary outcome was the rate of implementation. Secondary outcomes included
endometritis and other postoperative complications. RESULTS: The rate of
implementation after 6 months was 68.3% (p < .001) and postoperative endometritis
rates decreased from 14.0% before implementation to 11.7% after implementation (p
.49, OR 0.77, CI 0.36-1.62). Postoperative fever decreased from 22.3% to 18.3% (p
.256, OR 0.70, CI 0.37-1.30) and infectious wound complications were 4.5% and
5.8%, respectively (p .76, OR 1.07, CI 0.69-3.64). CONCLUSIONS: Implementation of
a protocol for vaginal cleansing prior to cesarean delivery in women with
ruptured membranes or in labor has high uptake, but in almost a third of eligible
women it was not performed. The implementation, has led to a clinical, although
not statistical, decrease in postoperative endometritis. Continued research is
needed to explore how to improve uptake of this quality improvement measure.
PMID- 29343135
TI - Genetic polymorphisms in folate metabolism as risk for Down syndrome in the
southern China.
AB - OBJECTIVE: To assess the association between maternal gene polymorphisms of the
enzymes involved in folate metabolism and the risk of having a Down syndrome (DS)
offspring in southern China mothers. METHODS: Gene polymorphisms in folate
metabolizing and the levels of homocysteine (HCY) were analyzed in 84 southern
China mothers with DS babies (the case group) and 120 healthy mothers (the
control group). Methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133) and
A1298C (rs1801131), methionine synthase (MTR) A2756G (rs1805087), and methionine
synthase reductase (MTRR) A66G (rs1801394) were studied. RESULTS: We found no
significant differences (p > .05) in the frequencies of four genetic
polymorphisms between the two groups. We found gene-gene interactions had a 1.997
fold increased risk in MTHFR 677 CT with MTR AA (OR: 1.997, 95% CI: 1.038-3.841,
p = .038) and a 2.588-fold increased risk in MTHFR 677 CT with MTRR AG (OR:
2.588, 95% CI: 1.111-6.031, p = .028) in the case group than control. The levels
of HCY were significantly higher in MTHFR 677 TT than MTHFR 677 CC in the case
group (TT 17.2167+/-5.1051, CC 12.1969+/-5.0299, F = 2.194, p < .05), and it was
significantly higher in MTHFR 677 TT in the case group than control (TT 17.2167+/
5.1051 in the case group, TT 10.2286+/-1.4373 in the control group, F = 2.546, p
< .05). CONCLUSION: These results suggest that genetic polymorphisms involved in
folate metabolism may have population specificity in determining the
susceptibility of having DS offsprings. The gene-nutrition, gene-gene
interactions and ethnicity are important variables to be considered in
periconceptional nutritional supplementation and antenatal care for reducing the
risk of DS babies.
PMID- 29343136
TI - Heme oxygenase activity increases after exercise in healthy volunteers.
AB - Heme oxygenase (HO) is an essential, rate-limiting protein which catalyses the
breakdown of heme to iron, carbon monoxide (CO), and biliverdin. The alpha
methene bridge of the heme is eliminated as CO which can be measured as blood
carboxyhaemoglobin (COHb). Using blood concentrations of COHb as a measure
reflecting HO activity, we tested the postulate that the activity of HO changes
with exercise. Ten healthy, nonsmoking volunteers (5 females and 5 males with a
mean age +/- standard deviation of 25.7 +/- 3.2 years), lifetime nonsmokers with
no history of respiratory diseases and not taking any medication, were included
in the study. Subjects were exposed to filtered air for 2 hrs while alternating
exercise for 15 minutes on a cycle ergometer with rest for 15 minutes. Workload
was adjusted so that subjects breathed at a ventilatory rate, normalised for body
surface area, of 25 L/m2/minute. Immediately before, immediately after, and the
day following exercise, blood was drawn by standard venipuncture technique. COHb
was determined using the interleukin (IL) 682 Co-Oximeter (Instrumentation
Laboratory, Bedford, MA). COHb increased in each participant during the exercise
session with the mean value (+/- standard deviation) almost doubling (1.1 +/- 1.6
to 2.1 +/- 1.6%) and returned to baseline by the following day (1.3 +/- 1.3%). We
conclude that exercise increases HO activity.
PMID- 29343137
TI - Hybrid aortic arch and frozen elephant trunk reconstruction: bridging the gap
between conventional and total endovascular arch repair.
AB - INTRODUCTION: Novel endovascular techniques hope to offer patients aortic arch
repair with reduced morbidity compared to conventional arch surgery; however,
current endovascular strategies remain challenged by the proximal seal zone,
higher stroke rates, long-term durability and select anatomy. Hybrid arch repair
offers patients a less invasive alternative that can treat more distal aorta than
conventional arch repair yet still be performed via standard sternotomy. Areas
covered: This review will discuss the current evidence and future development of
hybrid aortic arch and frozen elephant trunk reconstruction. Several approaches
to hybrid arch repair are summarized, including the off-label use of thoracic
endovascular stent-grafts and commercially manufactured hybrid grafts. Technical
considerations and clinical outcomes with each approach will be addressed along
with advantages and disadvantages. Expert commentary: Hybrid arch repair will
undergo continued refinement as our ability to provide a less-invasive
alternative to conventional open arch repair grows. Evolution to allow for
improved head vessel branch sizing, improved frozen elephant trunk deployment
accuracy, monitoring to prevent paraplegia and utilization of intraoperative
image guidance in hybrid operating rooms is necessary. The potential exists for
hybrid approaches to arch pathology to completely supplant conventional surgery,
while avoiding the potential deleterious complications of total endovascular
repair.
PMID- 29343138
TI - The efficacy of myo-inositol supplementation to prevent gestational diabetes
onset: a meta-analysis of randomized controlled trials.
AB - INTRODUCTION: The efficacy of myo-inositol supplementation to prevent gestational
diabetes onset remains controversial. We conducted a systematic review and meta
analysis to explore the influence of myo-inositol supplementation on the
incidence of gestational diabetes. METHODS: We search PubMed, Embase, Web of
science, EBSCO, and Cochrane Library databases through November 2017 for
randomized controlled trials (RCTs) assessing the effect of myo-inositol
supplementation on gestational diabetes onset. This meta-analysis is performed
using the random-effect model. RESULTS: Five randomized controlled trials (RCTs)
are included in the meta-analysis. Compared with control group in pregnant women,
myo-inositol supplementation is associated with significantly reduced incidence
of gestational diabetes (risk ratio (RR) = 0.43; 95%CI = 0.21-0.89; p = .02), and
preterm delivery (RR = 0.36; 95%CI = 0.17-0.73; p = .005), but has no substantial
impact on 2-h glucose oral glucose tolerance test (OGTT) (mean difference (MD) =
6.90; 95%CI = -15.07 to 1.27; p = .10), gestational age at birth (MD = 0.74;
95%CI = -1.06 to 2.54; p = .42), birth weight (MD = -5.50; 95%CI = -116.99 to
105.99; p = .92), and macrosomia (RR = 0.65; 95%CI = 0.20-2.11; p = .47).
CONCLUSIONS: Myo-inositol supplementation has some ability to reduce the
incidence of gestational diabetes and preterm delivery in pregnant women.
PMID- 29343139
TI - The impact of medical school assessment on preparedness for practice.
AB - PURPOSE: As assessment is known to drive learning, this paper looks at the
relationship between assessment practice across UK medical schools and graduates
preparedness for practice. MATERIALS AND METHODS: It uses data on written and
practical assessment at each medical school and the association with students'
self-reported preparedness for working as a foundation doctor on graduation, and
in particular the preparation related to clinical skills. RESULTS AND
CONCLUSIONS: A negative correlation (beta= -0.003, p < 0.001) was observed
between total duration of written assessment and preparedness, while a positive
relationship (beta = 0.461, p < 0.001) was seen between "adequately prepared" and
the proportion of all assessment time focusing on practical skills. This suggests
that graduates from medical schools with a greater emphasis on practical skills
in their assessment plan are better prepared to practice as a junior doctor on
gradation; something that may be of relevance when designing a national licensing
examination.
PMID- 29343140
TI - A heterogeneous tissue model for treatment planning for magnetic resonance-guided
laser interstitial thermal therapy.
AB - We evaluated a physics-based model for planning for magnetic resonance-guided
laser interstitial thermal therapy for focal brain lesions. Linear superposition
of analytical point source solutions to the steady-state Pennes bioheat transfer
equation simulates laser-induced heating in brain tissue. The line integral of
the photon attenuation from the laser source enables computation of the laser
interaction with heterogeneous tissue. Magnetic resonance thermometry data sets
(n = 31) were used to calibrate and retrospectively validate the model's thermal
ablation prediction accuracy, which was quantified by the Dice similarity
coefficient (DSC) between model-predicted and measured ablation regions (T > 57
degrees C). A Gaussian mixture model was used to identify independent tissue
labels on pre-treatment anatomical magnetic resonance images. The tissue
dependent optical attenuation coefficients within these labels were calibrated
using an interior point method that maximises DSC agreement with thermometry. The
distribution of calibrated tissue properties formed a population model for our
patient cohort. Model prediction accuracy was cross-validated using the
population mean of the calibrated tissue properties. A homogeneous tissue model
was used as a reference control. The median DSC values in cross-validation were
0.829 for the homogeneous model and 0.840 for the heterogeneous model. In cross
validation, the heterogeneous model produced a DSC higher than that produced by
the homogeneous model in 23 of the 31 brain lesion ablations. Results of a
paired, two-tailed Wilcoxon signed-rank test indicated that the performance
improvement of the heterogeneous model over that of the homogeneous model was
statistically significant (p < 0.01).
PMID- 29343141
TI - Novel beta-lactam/beta-lactamase inhibitors versus alternative antibiotics for
the treatment of complicated intra-abdominal infection and complicated urinary
tract infection: a meta-analysis of randomized controlled trials.
AB - INTRODUCTION: The aim of this study is to compare the efficacy and safety of
novelBL/BLIs with alternative antibiotics for the treatment of cIAI and cUTI.
Area covered: We performed a systematic review and meta-analysis of all
randomized controlled trials comparing novel BL/BLIs with other antibiotics for
the treatment of cIAI and cUTI. The primary outcome included clinical and
microbiological treatment success. Expert commentary: We found that novel BL/BLIs
obtained a similar clinical outcome with other antibiotics in CE population (OR =
1.07, 95%CI = (0.80, 1.44), P = 0.64). However, novel BL/BLIs had better clinical
treatment success in the cUTI subgroup (OR = 2.14, 95%CI = (1.06, 4.31), P =
0.03). Furthermore, novel BL/BLIs achieved significant microbiological treatment
success in patie nts with cUTI (OR = 1.70, 95%CI = (1.29, 2.25), P = 0.0002)
and had higher eradication rates for Gram-negative pathogens (OR = 1.82, 95%CI =
(1.26, 2.64), P = 0.001) including E.coli and K.pneumoniae. No difference was
observed concerning the incidence of mortality and adverse events between the two
groups. Therefore, we concluded that novel BL/BLIs are not inferior to other
available antibiotics for the treatment of cIAI, and they have advantages in
patients with cUTI. Simultaneously, they are sensitive to Gram-negative
pathogens, especially for E.coli and K.pneumoniae.
PMID- 29343142
TI - A 500 U/2 mL dilution of abobotulinumtoxinA vs. placebo: randomized study in
cervical dystonia.
AB - : Purpose/aim: AbobotulinumtoxinA (Dysport(r), Ipsen Biopharmaceuticals, Inc.,
Basking Ridge, NJ, USA) is an acetylcholine release inhibitor and a neuromuscular
blocking agent. The United States prescribing information for abobotulinumtoxinA
previously indicated only one dilution for cervical dystonia: 500 U/1 mL.
Clinical trial data supporting a larger volume with a 500 U/2 mL dilution would
offer clinicians flexibility with injection volume to better meet patient needs.
MATERIALS AND METHODS: We conducted a 12-week, phase 3b, multicenter, randomized,
double-blind, placebo-controlled trial (NCT01753310). Adult subjects with a
primary diagnosis of cervical dystonia were randomized (2:1) to receive a single
injection of either abobotulinumtoxinA, 500 U/2 mL dilution, or placebo. The
primary efficacy endpoint was changed from baseline in Toronto Western Spasmodic
Torticollis Rating Scale total score at Week 4. RESULTS: A total of 134 subjects
(abobotulinumtoxinA, n = 89; placebo, n = 45) were randomized (intent-to-treat
population) and 129 (abobotulinumtoxinA, n = 84; placebo, n = 45) completed the
Week 4 primary endpoint evaluation (modified intent-to-treat population). In the
modified intent-to-treat population, subjects receiving abobotulinumtoxinA
experienced significantly greater changes from baseline versus placebo on the
primary endpoint (weighted overall treatment difference -8.3, P < 0.001). The
most common treatment-emergent adverse events (TEAEs) were dysphagia, muscle
weakness, neck pain and headache. Overall, TEAEs were consistent with those
reported in the abobotulinumtoxinA prescribing information (1 mL dilution) for
cervical dystonia patients. CONCLUSIONS: This trial provides evidence that a 500
U/2 mL dilution is an effective treatment for cervical dystonia and exhibits a
safety profile consistent with the known safety profile of abobotulinumtoxinA.
PMID- 29343143
TI - Colorectal cancer patients' preferences for type of caregiver during survivorship
care.
AB - PURPOSE: Colorectal cancer (CRC) survivors are currently included in a secondary
care-led survivorship care programme. Efforts are underway to transfer this
survivorship care to primary care, but met with some reluctance by patients and
caregivers. This study assesses (1) what caregiver patients prefer to contact for
symptoms during survivorship care, (2) what patient factors are associated with a
preferred caregiver, and (3) whether the type of symptom is associated with a
preferred caregiver. METHODS: A cross-sectional study of CRC survivors at
different time points. For 14 different symptoms, patients reported if they would
consult a caregiver, and who they would contact if so. Patient and disease
characteristics were retrieved from hospital and general practice records.
RESULTS: Two hundred and sixty patients participated (response rate 54%) of whom
the average age was 67, 54% were male. The median time after surgery was seven
months (range 0-60 months). Patients were divided fairly evenly between tumour
stages 1-3, 33% had received chemotherapy. Men, patients older than 65 years, and
patients with chronic comorbid conditions preferred to consult their general
practitioner (GP). Women, patients with stage 3 disease, and patients that had
received chemotherapy preferred to consult their secondary care provider. For all
symptoms, patients were more likely to consult their GP, except for (1) rectal
blood loss, (2) weight loss, and (3) fear that cancer had recurred, in which case
they would consult both their primary and secondary care providers. Patients
appreciated all caregivers involved in survivorship care highly; with 8 out of 10
points. CONCLUSIONS: CRC survivors frequently consult their GP in the current
situation, and for symptoms that could alarm them to a possible recurrent disease
consult both their GP and secondary care provider. Patient and tumour
characteristics influence patients' preferred caregiver.
PMID- 29343144
TI - Cell-surface proteomics for the identification of novel therapeutic targets in
cancer.
AB - INTRODUCTION: Cancer is the second most common cause of death worldwide and its
heterogeneity complicates therapy. Standard cytotoxic regiments disrupt rapidly
dividing cells, regardless of their neoplastic status. The introduction of less
toxic targeted therapies has partially contributed to the observed decrease in
cancer-related mortality. Cell-surface proteins represent attractive targets for
therapy, due to their easily-accessible localization and their involvement in
essential signaling pathways, often dysregulated in cancer. Despite their
clinical appeal, cell-surface proteins are often underrepresented in standard
proteomic data sets, due to their poor solubility and lower expression levels
compared to intracellular proteins. Areas covered: This review will summarize
some of the available techniques for enriching the cell-surface proteome, and
discuss their advantages, limitations and applicability to clinical sample
testing. Moreover, we discuss currently available strategies for the development
of novel targeted therapies in cancer. Expert commentary: The interest in
elucidating the cancer-associated surfaceome is growing and will likely benefit
from recent advancements in instrument sensitivity, method development, and a
growing body of high-quality proteomics databases. Multiomics studies, in
combination with functional validations (e.g. dropout screens), and evaluation of
the healthy surfaceome, will likely aid in the selection of relevant targets for
future therapy development.
PMID- 29343145
TI - Principles of focused ultrasound.
AB - Focused ultrasound (FUS/HIFU) relies on ablation of pathological tissues by
delivering a sufficiently high level of acoustic energy in situ of the human
body. Magnetic Resonance guided FUS (MRgFUS/HIFU) and Ultrasound guided
(USgFUS/HIFU) are image guided techniques combined with therapeutic FUS for
monitoring purposes. The principles and technologies of FUS/HiFU are described in
this paper including the basics of MR guidance techniques and MR temperature
mapping. Clinical applications of FUS/HIFU gained CE and FDA approvals for the
treatment of various benign and few malignant lesions in the last two decades.
Current technical limitations of ultrasound guided and MRI guided Focused
Ultrasound, as well as adverse effects for the application of this technique are
outlined including challenges of ablating moving organs (liver and kidney). An
outlook to possible applications is provided; exampling clinical trials
discussing future options.
PMID- 29343146
TI - Induction of labor in cases of late preterm isolated oligohydramnios: is it
justified?
AB - OBJECTIVES: To analyze in a retrospective cohort study the outcomes of
pregnancies with isolated oligohydramnios at the late preterm period (34-36.6
weeks of gestation). STUDY DESIGN: This retrospective cohort study included three
groups of women: (1) Women with isolated oligohydramnios whose pregnancy was
managed conservatively (n = 33 births); (2) women with isolated oligohydramnios
who were managed actively (i.e. induction of labor) (n = 111 births); and (3) a
control group including women with normal amount of amniotic fluid who had a
spontaneous late preterm delivery (n = 10,445 births). Maternal and fetal
characteristics and obstetrics outcomes were collected from a computerized
database of all deliveries at Soroka University Medical Center during the study
period. RESULTS: Our cohort included 10,589 births. The rate of inducing labor
was higher in the oligohydramnios groups compared to the controls (p < .001).
There was an increase in the rate of cesarean section (CS) in the conservative
treatment group (p < .001), compared with the other groups. Conservative
management was associated with higher rates of maternal infection (p = .026),
chorioamnionitis (p = .01), and transitory tachypnea of the newborn (p = .02).
After controlling for confounding factors, mal presentation (OR = 19.9), and a
prior CS (OR = 2.4) were independently associated with an increased risk for CS,
while induction of labor was associated with a reduced risk for CS (OR = 0.28).
CONCLUSIONS: Women with late preterm isolated oligohydramnios had a higher rate
of induction of labor than women with a normal amount of amniotic fluid.
Induction of labor seems to be beneficial to both the neonate and the mother as
seen by a lower rate of CS conducted in this group, as well as lower maternal and
neonatal morbidity in comparison to the conservative group. Therefore, women with
oligohydramnios at late preterm may benefit from induction of labor.
PMID- 29343147
TI - Estimation of intra-arterial chemotherapy distribution to the retina in pediatric
retinoblastoma patients using quantitative digital subtraction angiography.
AB - Background and purpose The purpose of this article is to estimate the
distribution of superselective intra-arterial chemotherapy (IAC) delivery to
ocular target tissue using quantitative digital subtraction angiography (qDSA).
Materials and methods From March 2010 to January 2016, 50 ophthalmic artery
contrast DSAs obtained immediately prior to IAC infusions in 22 patients were
analyzed. This study was conducted under a retrospective review IRB (no. 10
01862). Parametric color-coded DSAs (iFlow, Siemens Medical) were post-processed
(MATLAB, The Mathworks Inc.) using two methods: two box regions of interest (pre
retina and globe) and four custom regions of interest (ROIs-ophthalmic artery,
choroid, supraclinoid internal carotid artery (ICA), cavernous ICA). Mean
interobserver reliability of custom ROI selection is presented as a 95%
confidence interval of interclass correlation, and fractional chemotherapy
delivery to selected ROIs as means +/- standard deviation in this study. Results
The estimated fraction of chemotherapy delivered to the globe with the first
method was 79.5%. Percentage regional delivery using the second method was as
follows: ophthalmic artery, 85.8%; choroid, 60.5%; supraclinoid ICA, 14.2%. The
cavernous ICA ROI (encompassing distal catheter and potential reflux) gave a
signal equivalent to 9.3% of total delivery. Conclusion Parametric color-coded
qDSA can estimate the fraction of IAC delivered to the retina and other orbital
structures in ocular retinoblastoma patients. This information can inform
delivery location and dosing strategies on a patient-specific basis.
PMID- 29343149
TI - Interventional bronchoscopy in adults.
AB - INTRODUCTION: The field of interventional pulmonology (IP) is a rapidly maturing
subspecialty of pulmonary medicine, which emphasizes advanced diagnostic and
therapeutic bronchoscopy for the evaluation and management of central airway
obstruction, mediastinal/hilar adenopathy and lung nodules/masses, as well as
minimally invasive diagnostic and therapeutic pleural procedures. Areas covered:
This review describes advances in diagnostic and therapeutic bronchoscopic
techniques. Expert commentary: In the past decade, there has been a remarkable
growth in available technology and equipment, as well as clinical and
translational research efforts focused on patient-centered outcomes. Furthermore,
the recent establishment of a uniform accreditation standard for all IP
fellowship programs in the United States was an important step in the continued
evolution of this subspecialty of pulmonary medicine.
PMID- 29343148
TI - Predictors of intracranial hemorrhage volume and distribution in brain
arteriovenous malformation.
AB - Background and purpose Despite evidence regarding risk factors for brain
arteriovenous malformation (bAVM)-associated spontaneous intracranial hemorrhage
(ICH), few data exist describing the spectrum of clinical outcomes that bAVM
associated ICH may manifest. This study aimed to identify the demographical,
clinical, and bAVM anatomical variables associated with ICH volume and the
presence of intraventricular hemorrhage (IVH) of ruptured bAVMs, two indicators
of worse clinical outcome, to help better predict outcome for unruptured bAVMs.
Methods Computed tomography images ( n = 169) of patients with ruptured bAVM in a
prospectively maintained institutional database were retrospectively reviewed to
calculate ICH volume and the presence or absence of IVH. Demographic, clinical,
and bAVM characteristics information was summarized and analyzed with univariable
and multivariable regression models to identify the associations of these
features with ICH volume and the presence of IVH. Results Patient sex,
exclusively deep venous drainage, and lobar location were associated with ICH
volume in univariable analysis; exclusively deep venous drainage remained
significant in multivariable analysis (PI = 0.33, 95% CI: 0.21-0.52, p < 0.001).
Exclusively deep venous drainage, multiple feeding arteries, and venous stenosis
were associated with IVH in univariable analysis; exclusively deep venous
drainage (OR = 7.27, 95% CI: 1.94-27.29, p = 0.003) remained significant in
multivariable analysis. Conclusions Variables associated with ICH volume and the
presence of IVH in ruptured bAVMs were evaluated and identified. They impart
information that may help predict the clinical outcome of unruptured bAVM, in
turn aiding clinicians in treatment planning.
PMID- 29343150
TI - Eight-year outcomes of a competency-based residency training program in
orthopedic surgery.
AB - BACKGROUND: The Division of Orthopaedic Surgery at the University of Toronto
implemented a pilot residency training program that used a competency-based
framework in July of 2009. The competency-based curriculum (CBC) deployed an
innovative, modularized approach that dramatically intensified both the
structured learning elements and the assessment processes. METHODS: This paper
discusses the initial curriculum design of the CBC pilot program; the refinement
of the curriculum using curriculum mapping that allowed for efficiencies in
educational delivery; details of evaluating resident competence; feedback from
external reviews by accrediting bodies; and trainee and program outcomes for the
first eight years of the program's implementation. RESULTS: Feedback from the
residents, the faculty, and the postgraduate residency training accreditation
bodies on the CBC has been positive and suggests that the essential framework of
the program may provide a valuable tool to other programs that are contemplating
embarking on transition to competency-based education. CONCLUSIONS: While the
goal of the program was not to shorten training per se, efficiencies gained
through a modular, competency-based program have resulted in shortened time to
completion of residency training for some learners.
PMID- 29343151
TI - Correction to: Carpen et al., Presenting symptoms and clinical findings in HPV
positive and HPV-negative oropharyngeal cancer patients.
PMID- 29343152
TI - Impact of dosage timing on the bioavailability of oral anticancer medications: Is
pre-prandial dosing equivalent to post-prandial dosing.
AB - Many oral anticancer agents are recommended to be given either at least 1 h
before or 2 h after a meal, according to the prescribing information. However,
the effect of dosage timing of an oral anticancer agent with reference to food
intake on anticancer treatment remains unclear. As shown by the literature survey
and labeling analysis for oral anticancer drugs approved by the US Food and Drug
Administration from 2010 to 2016, labeling information regarding dosage timing
for several anticancer drugs appeared not be optimum, leading to suboptimal
bioavailability and plasma drug concentrations. This supports a call to regularly
recalibrate the labeling information for dosage timing of oral anticancer
medications to minimize the risks of compromised efficacy or unintended
toxicities.
PMID- 29343153
TI - Cryptococcal infections in two patients receiving ibrutinib therapy for chronic
lymphocytic leukemia.
AB - Cryptococcal infections are responsible for significant morbidity and mortality
in immunocompromised patients. Reports of these infections in patients on small
molecular kinase inhibitors have not been widely reported in clinical trials. We
describe one case of cryptococcal meningoencephalitis and one case of
cryptococcal pneumonia in two patients who were receiving ibrutinib for chronic
lymphocytic leukemia. Despite different sites of cryptococcal infection, both
patients had similar presentations of acute illness. Patient 1 was worked up for
health care-associated pneumonia, as well as acute sinusitis prior to the
diagnosis of cryptococcal meningoencephalitis. He also had a more complex past
medical history than patient 2. Patient 2 developed atrial fibrillation from
ibrutinib prior to admission for presumed health care-associated pneumonia.
Cryptococcal antigen testing was done sooner in this patient due to patient
receiving high-dose steroids for the treatment of underlying hemolytic anemia. We
conclude that patients who develop acute illness while receiving ibrutinib should
be considered for cryptococcal antigen testing.
PMID- 29343154
TI - Dasatinib-induced pulmonary arterial hypertension - A rare late complication.
AB - Dasatinib is a dual Src/Abl tyrosine kinase inhibitor approved for frontline and
second line treatment of chronic phase chronic myelogenous leukemia. Pulmonary
arterial hypertension is defined by an increase in mean pulmonary arterial
pressure >25 mmHg at rest. Dasatinib-induced pulmonary hypertension has been
reported in less than 1% of patients on chronic dasatinib treatment for chronic
myelogenous leukemia. The pulmonary arterial hypertension from dasatinib may be
categorized as either group 1 (drug-induced) or group 5 based on various
mechanisms that may be involved including the pathogenesis of the disease process
of chronic myelogenous leukemia. There have been reports of dasatinib-induced
pulmonary arterial hypertension being reversible. We report a case of pulmonary
arterial hypertension in a 46-year-old female patient with chronic phase chronic
myelogenous leukemia on dasatinib treatment for over 10 years. She had
significant improvement in symptoms after discontinuation of dasatinib and
initiation of vasodilators. Several clinical questions arise once patients
experience significant adverse effects as discussed in our case.
PMID- 29343155
TI - Carboxymethyl chitosan-zinc coating for prevention of pin tract infection: An
animal model.
AB - BACKGROUND: Pin tract infection is a common problem in orthopedic and
traumatology surgery. The aim of this study was to investigate the efficacy of an
implant coated with carboxymethyl chitosan-zinc (CMC-Zn2+) in prevention of pin
tract infection. MATERIALS AND METHODS: Twenty-four male New Zealand White
rabbits were randomized into two equal groups ( n = 12, uncoated and CMC-Zn2+).
The implants were colonized with 1 * 106 colony forming units of Staphylococcus
aureus and inserted into the lateral right proximal tibia in each rabbit. In each
group, at 2 and 4 weeks post-surgery, five and seven rabbits were killed,
respectively, to harvest the soft tissues around the implant as well as the hard
tissue for histological analysis. The bone cross-sectional view, X-ray, and micro
computed tomography (MUCT) were performed. RESULTS: The surgical sites in each
animal were evaluated individually at both time points. No evident signs of
infections were found in the CMC-Zn2+ group, while a high rate of infection was
observed in the uncoated group where minor infections were 85.71% ( n = 12) and
major infections 14.29% ( n = 12). The radiography, MUCT, and histological
analysis showed no evident signs of infection in both groups at 2 weeks post
surgery. However, at 4 weeks, signs of infection were found in all the animals in
the uncoated group, whereas in the CMC-Zn2+ group, no infections were observed.
The difference between the two groups was highly significant ( p = 0.00).
CONCLUSIONS: Our study showed that CMC-Zn2+-coated implants were effective in
preventing pin tract infection.
PMID- 29343156
TI - Patient contributions during primary care consultations for hypertension after
self-reporting via a mobile phone self-management support system.
AB - OBJECTIVE: This paper reports on how the clinical consultation in primary care is
performed under the new premises of patients' daily self-reporting and self
generation of data. The aim was to explore and describe the structure, topic
initiation and patients' contributions in follow-up consultations after eight
weeks of self-reporting through a mobile phone-based hypertension self-management
support system. DESIGN: A qualitative, explorative study design was used,
examining 20 audio- (n = 10) and video-recorded (n = 10) follow-up consultations
in primary care hypertension management, through interaction analysis. Clinical
trials registry: ClinicalTrials.gov NCT01510301. SETTING: Four primary health
care centers in Sweden. SUBJECTS: Patients with hypertension (n = 20) and their
health care professional (n = 7). RESULTS: The consultations comprised three
phases: opening, examination and closing. The most common topic was blood
pressure (BP) put in relation to self-reported variables, for example, physical
activity and stress. Topic initiation was distributed symmetrically between
parties and BP talk was lifestyle-centered. The patients' contributed to the
interpretation of BP values by connecting them to specific occasions, providing
insights to the link between BP measurements and everyday life activities.
CONCLUSION: Patients' contribution through interpretations of BP values to
specific situations in their own lives brought on consultations where the patient
as a person in context became salient. Further, the patients' and health care
professionals' equal contribution during the consultations showed actively
involved patients. The mobile phone-based self-management support system can thus
be used to support patient involvement in consultations with a person-centered
approach in primary care hypertension management Key points The clinical
consultation is important to provide opportunities for patients to gain
understanding of factors affecting high blood pressure, and for health care
professionals to motivate and promote changes in life-style. This study shows
that self-reporting as base for follow-up consultations in primary care
hypertension management can support patients and professionals to equal
participation in clinical consultations. Self-reporting combined with increased
patient-health care professional interaction during follow-up consultations can
support patients in understanding the blood pressure value in relation to their
daily life. These findings implicate that the interactive mobile phone self
management support system has potential to support current transformations of
patients as recipients of primary care, to being actively involved in their own
health.
PMID- 29343157
TI - The clinician-educator has no clothes.
PMID- 29343159
TI - Celebrating 40 years of Medical Teacher: As the "last man standing" I look back
to help us look forward.
AB - INTRODUCTION: In this reflective, descriptive, analytical, first-person piece, I
offer recollections, data, and literature to help elucidate the emergence of
medical education as a scholarly field, as part of celebrating Medical Teacher's
40-year anniversary. I emphasize the impressive growth of the professional
literature in medical education, and recognize that much remains to be done.
FINDINGS: Medical education as a domain for research and development has
transitioned from being largely ignored during the first 20 of the past 60 years,
through a slow growth phase, to rapid acceleration during the last 2 decades. By
introducing the use and potential of "edumarkers," we can see that medical
education as a focus of scholarly pursuits was absent to minimal before recent
decades, and we can identify trends and questions that deserve further
exploration. Concern and recommendations: Only a small subset of the large
population assigned to instruct health professions learners actually conducts and
responds to medical education scholarship. I raise several questions as possible
guides to the future for those of us who are devoted to enhancing educational
processes and outcomes for learners who are expected to help prevent and manage
the health challenges faced by the world's people.
PMID- 29343158
TI - Placebo Effects in Traumatic Brain Injury.
AB - In recent years, several randomized controlled trials evaluating pharmaceutical
treatments for traumatic brain injury (TBI) have failed to demonstrate efficacy
over placebo, with both active and placebo arms improving at comparable rates.
These findings could be viewed in opposing ways, suggesting on the one hand
failure of the tested outcome, but on the other, representing evidence of robust
placebo effects in TBI. In this article, we examine several of the primary
psychological processes driving placebo effects (verbal suggestion, cognitive re
framing, interpersonal interactions, conditioning, therapeutic alliance, anxiety
reduction) as well as placebo neurobiology (top-down cortical regulation, reward
system activation, dopaminergic and serotonergic neurotransmission). We then
extrapolate from the literature to explore whether something inherent in TBI
makes it particularly responsive to placebos. Viewed as such here, placebos may
indeed represent a powerful and effective treatment for a variety of post-TBI
complaints.
PMID- 29343160
TI - Public School Nursing Practice in the United States.
AB - School nursing practice has changed dramatically over the past 20 years, yet few
nationally representative investigations describing the school nursing workforce
have been conducted. The National School Nurse Workforce Study describes the
demographic and school nursing practice patterns among self-reported public
school nurses and the number and full-time equivalent (FTE) positions of all
school nurses in the United States. Using a random sample stratified by
public/private, region, school level, and urban/rural status from two large
national data sets, we report on weighted survey responses of 1,062 public
schools. Additional questions were administered to estimate the school nurse
population and FTEs. Findings reported illustrate differences by strata in public
school nurse demographics, practice patterns, and nursing activities and tasks.
We estimate approximately 132,300 self-identified practicing public and private
school nurses and 95,800 FTEs of school nurses in the United States. Research,
policy, and school nursing practice implications are discussed.
PMID- 29343162
TI - Psychopathy and Victim Selection: Does Nonverbal Decoding or Empathy Impact
Vulnerability Ratings?
AB - This research examined the role of psychopathic traits in perceptions of
victimization and vulnerability. Community-member participants viewed video clips
of victims, nonvictims, and victims who studied self-defense, then rated them on
vulnerability and perceived history of victimization. Participants were most
proficient at identifying nonvictims as nonvictims. Victims who studied self
defense were harder to correctly identify than both victims and nonvictims and
were rated by participants as less vulnerable and less likely to be victims than
other victims and nonvictims. Moreover, individuals high in psychopathic traits,
specifically Factor 2, were more likely than individuals low in psychopathic
traits to correctly identify victims who practiced self-defense as victims, as
well as nonvictims as victims. Unexpectedly, there was an observed negative
relationship between facial affect decoding and identifying self-defense victims.
The ability to correctly interpret facial expressions was found to partially
mediate the relationship between psychopathy scores and the identification of
self-defense victims. The results of this study provide insight into the ability
of individuals with psychopathic traits to identify nonverbal cues associated
with vulnerability. The results provide evidence that taking self-defense classes
may be a meaningful intervention for victims, particularly.
PMID- 29343163
TI - Magnetic resonance imaging changes following natalizumab discontinuation in
multiple sclerosis patients with progressive multifocal leukoencephalopathy.
AB - BACKGROUND: Detecting early progressive multifocal leukoencephalopathy-immune
reconstitution inflammatory syndrome (PML-IRIS) is clinically relevant.
OBJECTIVE: Evaluating magnetic resonance imaging (MRI) changes following
natalizumab (NTZ) discontinuation and preceding PML-IRIS. METHODS: MRIs
(including diffusion-weighted imaging (DWI), T2-weighted fluid-attenuated
inversion recovery (T2-FLAIR), post-contrast T1-weighted sequences) were
performed every week following PML diagnosis in 11 consecutive NTZ-PML patients.
PML expansion, punctate lesions, contrast-enhancement, and mass-effect/edema were
evaluated on each MRI sequence, following NTZ discontinuation. RESULTS: PML-IRIS
occurred from 26 to 89 days after NTZ discontinuation. MRI changes prior to early
PML-IRIS appeared significantly more pronounced using DWI compared to T2-FLAIR
imaging ( p < 0.003). Two DWI features (marked PML expansion, punctate lesions)
systematically preceded contrast-enhancement. CONCLUSION: Subtle changes may
occur on DWI preceding contrast-enhancement.
PMID- 29343161
TI - Addressing the Social Determinants of Health: A Call to Action for School Nurses.
AB - Social determinants of health (SDOH), the conditions in which children are born,
grow, live, work or attend school, and age, impact child health and contribute to
health disparities. School nurses must consider these factors as part of their
clinical practice because they significantly and directly influence child well
being. We provide clinical guidance for addressing the SDOH when caring for
children with three common health problems (obesity, insufficient sleep, and
asthma). Given their unique role as school-based clinical experts, care
coordinators, and student advocates, school nurses are well suited to serve as
leaders in addressing SDOH.
PMID- 29343164
TI - Inflammatory and Oxidative Responses in Pregnancies With Obesity and Periodontal
Disease.
AB - BACKGROUND: Maternal obesity is related to immunologic and inflammatory systemic
modifications that may worsen the pregnancy inflammatory status. Hormonal changes
during pregnancy can adversely affect oral biofilms and oral health initiating or
worsening periodontal diseases, with enhanced local and systemic oxidative stress
and inflammation. OBJECTIVE: The aim of this study was to examine the
relationship between local salivary and systemic parameters of oxidative stress
and inflammation in relation to obesity and periodontal diseases. STUDY DESIGN:
Sixty-two women with singleton pregnancies were enrolled. Twenty-seven women were
normal weight (NW; 18.5< body mass index [BMI] <25 kg/m2) and 35 obese (BMI >=30
kg/m2). Seventeen of the obese had gestational diabetes mellitus (GDM). During
third trimester, periodontal status was evaluated, saliva (s) was collected to
assess total antioxidant capacity (s-TAC) and C-reactive protein (s-CRP) levels,
and venous plasma (p) was used to measure CRP levels (p-CRP). Maternal, fetal,
and placental data were registered at delivery. RESULTS: Levels of s-TAC, s-CRP,
and p-CRP were significantly higher in obese, particularly in the presence of
GDM, compared to NW and related to each other ( P = .000; r > 0.59), to maternal
BMI ( P = .000; r > 0.52), and fasting glycemia ( P < .002; r > 0.47).
Periodontal disease was more frequent in obese groups (80%) versus NW (52%; P =
.04), particularly when GDM was diagnosed ( P = .009). A significant interaction
effect between maternal BMI and oral condition was found for s-TAC levels. Obese
with periodontitis showed significant increase in local and systemic parameters
versus NW. CONCLUSION: Obesity and periodontal disease could synergistically
amplify the inflammatory and oxidative status, resulting in increased local and
systemic biomarkers particularly when GDM is diagnosed.
PMID- 29343165
TI - HIV and renal disease: a contemporary review.
AB - The presence of human immunodeficiency virus (HIV)-related kidney disease is an
important cause of mortality and morbidity. HIV infection induces renal injury by
direct cytotoxicity or immune complex-mediated glomerulonephritis in patients
with genetic susceptibility factors. In the last decades, with the development
and diffusion of combination antiretroviral therapy, which has prolonged patient
survival, there has been a shift in the spectrum of renal diseases in HIV
infected patients, with the decrease of glomerular diseases and increase in the
role of nephrotoxicity and co-morbidities. This review provides a contemporary
and critical review on the main renal syndromes occurring in HIV-infected
patients.
PMID- 29343166
TI - Consensus statement of the International Summit on Intellectual Disability and
Dementia on valuing the perspectives of persons with intellectual disability.
AB - The International Summit on Intellectual Disability and Dementia covered a range
of issues related to dementia and intellectual disability, including the dearth
of personal reflections of persons with intellectual disability affected by
dementia. This article reflects on this deficiency and explores some of the
personal perspectives gleaned from the literature, from the Summit attendees and
from the experiences of persons with intellectual disability recorded or scribed
in advance of the two-day Summit meeting. Systemic recommendations included
reinforcing the value of the involvement of persons with intellectual disability
in (a) research alongside removing barriers to inclusion posed by
institutional/ethics review boards, (b) planning groups that establish supports
for dementia and (c) peer support. Practice recommendations included (a) valuing
personal perspectives in decision-making, (b) enabling peer-to-peer support
models,
PMID- 29343167
TI - A cluster randomised feasibility trial of clinically assisted hydration in cancer
patients in the last days of life.
AB - BACKGROUND: The provision of clinically assisted hydration at the end-of-life is
one of the most contentious issues in medicine. AIM: The aim of this feasibility
study was to answer the question 'can a definitive (adequately powered) study be
done?' DESIGN: The study was a cluster randomised trial, with sites randomised on
a one-to-one basis to intervention 'A' (regular mouth care and usual other care)
or intervention 'B' (clinically assisted hydration, mouth care and usual other
care). Participants were assessed every 4 h, and data collected on clinical
problems, therapeutic interventions and overall survival. SETTING/PARTICIPANTS:
The study was conducted at 12 sites/'clusters' with specialist palliative care
teams (4 cancer centres and 8 hospices), and participants were cancer patients in
the last week of life who were unable to maintain sufficient oral fluid intake.
RESULTS: The study achieved its pre-determined criteria for success. Two hundred
patients were recruited to the study, and 199 participants completed the study,
over a 1-year period. A total of 38.5% participants discontinued clinically
assisted hydration due to adverse effects: none of these adverse events were
rated as 'severe' or worse in intensity. The primary reasons for discontinuation
were site problems ( n = 2), localised oedema ( n = 13), generalised oedema ( n =
5), respiratory secretions ( n = 6) and nausea and vomiting ( n = 1). CONCLUSION:
The results of this feasibility study suggest that a definitive study can be
done, but that minor changes are needed to the protocol to standardise the
administration of clinically assisted hydration (which may reduce the incidence
of certain adverse effects).
PMID- 29343168
TI - Assessment of goals and priorities in patients with a chronic condition: a
secondary quantitative analysis of determinants across 11 countries.
AB - OBJECTIVE: To assess the impact of patient characteristics, patient-professional
engagement, communication and context on the probability that healthcare
professionals will discuss goals or priorities with older patients. DESIGN:
Secondary analysis of cross-sectional data from the 2014 Commonwealth Fund
International Health Policy Survey of Older Adults. SETTING: 11 western
countries. SUBJECTS: Community-dwelling adults, aged 55 or older. MAIN OUTCOME
MEASURE: Assessment of goals and priorities. RESULTS: The final sample size
consisted of 17,222 respondents, 54% of whom reported an assessment of their
goals and priorities (AGP) by healthcare professionals. In logistic regression
model 1, which was used to analyse the entire population, the determinants found
to have moderate to large effects on the likelihood of AGP were information
exchange on stress, diet or exercise, or both. Country (living in Sweden) and
continuity of care (no regular professional or organisation) had moderate to
large negative effects on the likelihood of AGP. In model 2, which focussed on
respondents who experienced continuity of care, country and information exchange
on stress and lifestyle were the main determinants of AGP, with comparable odds
ratios to model 1. Furthermore, a professional asking questions also increased
the likelihood of AGP. CONCLUSIONS: Continuity of care and information exchange
is associated with a higher probability of AGP, while people living in Sweden are
less likely to experience these assessments. Further study is required to
determine whether increasing information exchange and professionals asking more
questions may improve goal setting with older patients. Key points A patient
goal-oriented approach can be beneficial for older patients with chronic
conditions or multimorbidity; however, discussing goals with these patients is
not a common practice. The likelihood of discussing goals varies by country,
occurring most commonly in the USA, and least often in Sweden. Country-level
differences in continuity of care and questions asked by a regularly visited
professional affect the goal discussion probability. Patient characteristics,
including age, have less impact than expected on the likelihood of sharing goals.
PMID- 29343169
TI - Patients' and carers' perspectives of palliative care in general practice: A
systematic review with narrative synthesis.
AB - BACKGROUND: General practitioners have overall responsibility for community care,
including towards end of life. Current policy places generalists at the centre of
palliative care provision. However, little is known about how patients and carers
understand the general practitioner's role. AIMS: To explore patient and carer
perspectives of (1) the role of the general practitioner in providing palliative
care to adult patients and (2) the facilitators and barriers to the general
practitioner's capacity to fulfil this perceived role. DESIGN: Systematic
literature review and narrative synthesis. DATA SOURCES: Seven electronic
databases (MEDLINE, Embase, PsycINFO, BNI, CINAHL, Cochrane and HMIC) were
searched from inception to May 2017. Two reviewers independently screened papers
at title, abstract and full-text stages. Grey literature, guideline, hand
searches of five journals and reference list/citation searches of included papers
were undertaken. Data were extracted, tabulated and synthesised using narrative,
thematic analysis. RESULTS: A total of 25 studies were included: 14 employed
qualitative methods, 8 quantitative survey methods and 3 mixed-methods. Five key
themes were identified: continuity of care, communication between primary and
secondary care, contact and accessibility, communication between general
practitioner and patient, and knowledge and competence. CONCLUSION: Although the
terminology and context of general practice vary internationally, themes relating
to the perceived role of general practitioners were consistent. General
practitioners are considered well placed to provide palliative care due to their
breadth of clinical responsibility, ongoing relationships with patients and
families, and duty to visit patients at home and coordinate healthcare resources.
These factors, valued by service users, should influence future practice and
policy development.
PMID- 29343170
TI - Accuracy of Ultrasonographic Measurements of Inferior Vena Cava to Determine
Fluid Responsiveness: A Systematic Review and Meta-Analysis.
AB - OBJECTIVE: Fluid responsiveness is the ability to increase the cardiac output in
response to a fluid challenge. Only about 50% of patients receiving fluid
resuscitation for acute circulatory failure increase their stroke volume, but the
other 50% may worsen their outcome. Therefore, predicting fluid responsiveness is
needed. In this purpose, in recent years, the assessment of the inferior vena
cava (IVC) through ultrasound (US) has become very popular. The aim of our work
was to systematically review all the previously published studies assessing the
accuracy of the diameter of IVC or its respiratory variations measured through US
in predicting fluid responsiveness. DATA SOURCES: We searched in the MEDLINE
(PubMed), Embase, Web of Science databases for all relevant articles from
inception to September 2017. STUDY SELECTION: Included articles specifically
addressed the accuracy of IVC diameter or its respiratory variations assessed by
US in predicting the fluid responsiveness in critically ill ventilated or not,
adult or pediatric patients. DATA EXTRACTION: We included 26 studies that
investigated the role of the caval index (IVC collapsibility or distensibility)
and 5 studies on IVC diameter. DATA SYNTHESIS: We conducted a meta-analysis for
caval index with 20 studies: The pooled area under the curve, logarithmic
diagnostic odds ratio, sensitivity, and specificity were 0.71 (95% confidence
interval [CI]: 0.46-0.83), 2.02 (95% CI: 1.29-2.89), 0.71 (95% CI: 0.62-0.80),
and 0.75 (95% CI: 0.64-0.85), respectively. CONCLUSION: An extreme heterogeneity
of included studies was highlighted. Ultrasound evaluation of the diameter of the
IVC and its respiratory variations does not seem to be a reliable method to
predict fluid responsiveness.
PMID- 29343171
TI - Prognosis of Acute Respiratory Distress Syndrome in Patients With Hematological
Malignancies.
AB - INTRODUCTION: The intensive care unit (ICU) admission of patients with
hematologic malignancies is gradually increasing. Life-threatening events are
common, and acute respiratory distress syndrome (ARDS) is one of the most
critical conditions. The aim of this study was to investigate the clinical
characteristics and outcomes of ARDS in patients with hematological malignancies
admitted to the ICU. METHODS: A retrospective study was performed on all patients
with ARDS with hematological malignancies in a single tertiary teaching hospital
between 2008 and 2015. Data on the treatment of and the outcomes of ARDS were
collected to determine the clinical characteristics associated with ICU
mortality. RESULTS: During the 8-year study period, among a total of 821 patients
with ARDS admitted to the ICU, all 185 patients with hematological malignancies
were included in the analysis. Most of the patients (88.1%) had moderate-to
severe ARDS, and the median PaO2/FiO2 ratio was 122 (interquartile range: 88
157). The overall ICU mortality rate was 57.3% (50.0% for mild, 52.0% for
moderate, and 67.7% for severe ARDS). After the univariate and the multivariate
logistic regressions, the factors independently associated with a higher ICU
mortality were severe ARDS (odds ratio [OR]: 2.47; 95% confidence interval [CI]:
1.17-5.25), identification of carbapenem-resistant gram-negative bacteria (OR:
6.61; 95% CI: 1.31-33.41), the amount of blood product transfusion (OR: 1.25; 95%
CI: 1.13-1.38), and the progressive or refractory disease (OR: 3.01; 95% CI: 1.31
6.91). Mortality was independently lower in patients who received the initial low
tidal volume ventilation (OR: 0.37, 95% CI: 0.14-0.96). CONCLUSION: The outcome
of ARDS in patients with hematological malignancies is associated with the
severity of the underlying diseases, the presence of multidrug-resistance
pathogens, and the amount of transfusion; however, strict application of low
tidal volume ventilation may improve the outcome of these patients at the time of
diagnosis.
PMID- 29343172
TI - Quantification of brake data acquired with a brake power meter during simulated
cross-country mountain bike racing.
AB - There is currently a dearth of information describing cycling performance outside
of propulsive and physiological variables. The aim of the present study was to
utilise a brake power meter to quantify braking during a multi-lap cross-country
mountain bike time trial and to determine how braking affects performance. A
significant negative association was determined between lap time and brake power
(800.8 +/- 216.4 W, mean +/- SD; r = -0.446; p < 0.05), while the time spent
braking (28.0 +/- 6.4 s) was positively associated with lap time (314.3 +/- 37.9
s; r = 0.477; p < 0.05). Despite propulsive power decreasing after the first lap
(p < 0.05), lap time remained unchanged (p > 0.05) which was attributed to
decreased brake work (p < 0.05) and brake time (p < 0.05) in both the front and
rear brakes by the final lap. A multiple regression model incorporating braking
and propulsion was able to explain more of the variance in lap time (r2 = 0.935)
than propulsion alone (r2 = 0.826). The present study highlights that riders'
braking contributes to mountain bike performance. As riders repeat a cross
country mountain bike track, they are able to change braking, which in turn can
counterbalance a reduction in power output. Further research is required to
understand braking better.
PMID- 29343173
TI - Effects of two feedback interventions on end-of-life outcomes in nursing home
residents with dementia: A cluster-randomized controlled three-armed trial.
AB - BACKGROUND: Despite increased attention for palliative care in dementia, recent
studies found burdensome symptoms and unmet family caregiver needs in the last
phase of life. Feedback is being used to improve the quality of palliative care,
but we do not know how effective it is. AIM: To assess the effect of two feedback
strategies on perceived quality of end-of-life care and comfort in dying nursing
home residents with dementia. METHODS: In a cluster-randomized controlled trial,
the End-of-Life in Dementia-Satisfaction With Care and the End-of-Life in
Dementia-Comfort Assessment in Dying scales were completed by bereaved family
caregivers of residents with dementia of 18 Dutch nursing homes. Two feedback
strategies, generic feedback with mean End-of-Life in Dementia-scores and
feedback with individual (patient-specific) End-of-Life in Dementia-scores, were
compared to no feedback provided. The intervention groups discussed End-of-Life
in Dementia-ratings in team meetings and formulated actions to improve care.
Multi-level analyses assessed effects. RESULTS: A total of 668 families rated the
End-of-Life in Dementia-instruments. Compared to no feedback, the generic
strategy resulted in lower quality of end-of-life care in unadjusted ( B = -1.65,
confidence interval = -3.27; -0.21) and adjusted analyses ( B = -2.41, confidence
interval = -4.07; -0.76), while there was no effect on comfort. The patient
specific strategy did not affect the quality of end-of-life care, but it
increased comfort in unadjusted analyses (only, B = 2.20, confidence interval =
0.15; 4.39; adjusted: B = 1.88, confidence interval = -0.34; 4.10). CONCLUSION:
Neither feedback strategy improved end-of-life outcome. Perhaps, skills to
translate the feedback into care improvement actions were insufficient. Feedback
with favorable family ratings might even have triggered opposite effects. Trial
number: NTR3942.
PMID- 29343174
TI - Small Molecules for Neural Stem Cell Induction.
AB - Generation of induced pluripotent stem cells (iPSCs) from other somatic cells has
provided great hopes for transplantation therapies. However, these cells still
cannot be used for clinical application due to the low reprogramming and
differentiation efficiency beside the risk of mutagenesis and tumor formation.
Compared to iPSCs, induced neural stem cells (iNSCs) are easier to terminally
differentiate into neural cells and safe; thus, iNSCs hold more opportunities
than iPSCs to treat neural diseases. On the other hand, recent studies have
showed that small molecules (SMs) can dramatically improve the efficiency of
reprogramming and SMs alone can even convert one kind of somatic cells into
another, which is much safer and more effective than transcription factor-based
methods. In this study, we provide a review of SMs that are generally used in
recent neural stem cell induction studies, and discuss the main mechanisms and
pathways of each SM.
PMID- 29343175
TI - Activity-Based Goals Generated by Older Adults With Mild Cognitive Impairment.
AB - Client-centered care is one promising rehabilitation model that may support the
unique needs of older adults with mild cognitive impairment (MCI). This secondary
analysis examined (a) whether older adults with MCI generated activity-based
goals using a client-centered model and (b) the types of goals generated.
Thirteen older adults with MCI addressed 55 goals. Using client-centered care,
the participants generated goals despite subtle limitations in activities and
participation. Participants generated the greatest number of goals related to
instrumental activities of daily living. This study demonstrated that older
adults with MCI generated goals through a client-centered model. This is
important because older adults with MCI are at risk for disability, and they may
benefit from early rehabilitation care models that minimize activity limitations
and participation restrictions despite underlying cognitive impairments.
PMID- 29343177
TI - Wide QRS alternans caused by propafenone toxicity.
PMID- 29343176
TI - On understanding the nature of interpersonal conflict between coaches and
athletes.
AB - Conflict is a part of coach-athlete relationships and should be carefully
considered as it can have effects on the quality of coaching and the level of
performance. Despite its practical relevance, there is a dearth of research
around coach-athlete conflict. Therefore, the current study aimed to explore the
characteristics and topics of conflict, as well as coaches and athletes'
emotional, cognitive and behavioural experiences during conflict. A total of 22
independent coaches and athletes participated in semi-structured interviews
evolving around the nature of interpersonal conflict. After all interviews were
transcribed, a deductive-inductive content analysis was conducted. This was
guided by the interview schedule as well as the by the conceptual framework of
conflict in sport relationships (Wachsmuth, Jowett, & Harwood, 2017). Data were
divided into five main categories: Conflict characteristics and conflict topics,
as well as conflict cognitions, emotions, and behaviours. Findings highlighted
the variety of ways in which participants understood and interpreted
interpersonal conflict and how their impressions of conflict influenced its
evolving process. Considering the participants' cognitive, emotional and
behavioural expressions of conflict, it became apparent that conflict can be
described through uncertain, escalating and problem-orientated responses.
Practical applications concerning (mal-) adaptive responses to conflict are
discussed. (199/200).
PMID- 29343178
TI - Impact of clinical pharmacists on atherosclerotic risk factor management in an
integrated heart and vascular clinic.
PMID- 29343179
TI - B-type natriuretic peptide for prediction of incident clinically significant
abdominal aortic aneurysm: A population-based prospective study.
AB - Pathogenesis of abdominal aortic aneurysm (AAA) is unclear. The aim of this study
was to evaluate inflammatory and hemodynamic plasma biomarkers as predictors for
AAA in the prospective longitudinal cohort of middle-aged individuals from the
cardiovascular cohort of the Malmo Diet and Cancer Study ( n=5551; 1991-94). C
reactive protein, cystatin C, copeptin, N-terminal pro-B-type natriuretic peptide
(N-BNP), midregional pro-atrial natriuretic peptide (MR-proANP) and conventional
risk factors at baseline were measured in patients with incident AAA during
follow-up and compared to individuals without a diagnosis of AAA. Subjects were
followed until 31 December 2013. Multivariable analyses were expressed in terms
of hazard ratios (HR) per 1 standard deviation increment of each respective log
transformed plasma biomarker in the Cox proportional hazard models. Mean follow
up time was 20.7 years. Cumulative incidence of AAA was 1.5% (men 2.9%, women
0.5%). Mean age of individuals with incident AAA was 59.7 years at study entry
and AAA was diagnosed on average 14 years later. Adjusting for age, sex, smoking,
body mass index, hypertension and diabetes mellitus, N-BNP (HR 1.29; 95% CI 1.03
1.62), but not MR-proANP (HR 1.20; 95% CI 0.95-1.50), was independently
associated with incident AAA. In conclusion, the plasma biomarker N-BNP was
associated with future development of AAA, which implies that this marker is a
sensitive indicator of early subclinical cardiovascular disease.
PMID- 29343180
TI - Images in Vascular Medicine: Standing waves are not distinctive to conventional
angiograms.
PMID- 29343181
TI - Experiencing abortion rights in India through issues of autonomy and legality: A
few controversies.
AB - Abortion laws in India, like other laws, are premised on the 1861 British Penal
Code. The Medical Termination of Pregnancy Act was passed in 1971 to circumvent
the criminality clause around abortion. Yet the law continues to render invisible
women's right to choose. Legal procedures have often hindered in permitting
abortion, resulting in the death of a mother or the foetus. Despite the latest
techno-medical advances, the laws have remained stagnant or rather restrictive,
complicated further by selective female foetus abortions. Legal resistance to
abortion-seeking after 20 weeks gestation adversely affects women, depriving them
of autonomy of choice. In this paper, raising important gender, health and
ethical issues are illustrated through a recent legal case in India. Feminist
campaigns against the legal mindset in India are emerging.
PMID- 29343182
TI - Fibronectin Enhances Cartilage Repair by Activating Progenitor Cells Through
Integrin alpha5beta1 Receptor.
AB - This study aimed to determine the effect of fibronectin (FN) on cartilage
regeneration through the activation of chondrogenic progenitor cells (CPCs).
Cells were isolated from the knee cartilage of mice and cultured in the presence
of various concentrations of FN. Proliferation, migration, and chondrogenic
differentiation assays were performed in vitro. In some experiments, CPCs were
preincubated with anti-integrin alpha5beta1 antibody for 60 min before FN
treatment to block the integrin alpha5beta1 receptor. Soluble FN was mixed with
Pluronic F-127 and injected into the joint cavity in an early-stage
osteoarthritis model. Cartilage repair was evaluated histologically,
biochemically, and biomechanically. In vitro, we observed that the isolated CPCs,
which exhibited stem cell-relevant markers, proliferated most at a concentration
of 20 MUg/mL FN (p < 0.05). In addition, FN enhanced the proliferation,
migration, and chondrogenic differentiation capacity of CPCs, and the enhancement
was significantly decreased by blockade of the integrin alpha5beta1 receptor (p <
0.05). In vivo, FN also significantly promoted cartilage repair along with
increased CPC activation and integrin alpha5beta1 expression (p < 0.05). These
findings suggest that FN enhances CPC proliferation, migration, and chondrogenic
differentiation through the integrin alpha5beta1-dependent signaling pathway.
Based on these results, a novel and promising therapy focused on targeted
activation of CPCs by FN could be developed for the treatment of cartilage
injuries in a clinical setting.
PMID- 29343183
TI - The acute angiogenic signalling response to low-load resistance exercise with
blood flow restriction.
AB - This study investigated protein kinase activation and gene expression of
angiogenic factors in response to low-load resistance exercise with or without
blood flow restriction (BFR). In a repeated measures cross-over design, six males
performed four sets of bilateral knee extension exercise at 20% 1RM (reps per set
= 30:15:15:continued to fatigue) with BFR (110 mmHg) and without (CON). Muscle
biopsies were obtained from the vastus lateralis before, 2 and 4 h post-exercise.
mRNA expression was determined using real-time RT-PCR. Protein
phosphorylation/expression was determined using Western blot. p38MAPK
phosphorylation was greater (p = 0.05) at 2 h following BFR (1.3 +/- 0.8)
compared to CON (0.4 +/- 0.3). AMPK phosphorylation remained unchanged. PGC
1alpha mRNA expression increased at 2 h (5.9 +/- 1.3 vs. 2.1 +/- 0.8; p = 0.03)
and 4 h (3.2 +/- 0.8 vs. 1.5 +/- 0.4; p = 0.03) following BFR exercise with no
change in CON. PGC-1alpha protein expression did not change following either
exercise. BFR exercise enhanced mRNA expression of vascular endothelial growth
factor (VEGF) at 2 h (5.2 +/- 2.8 vs 1.7 +/- 1.1; p = .02) and 4 h (6.8 +/- 4.9
vs. 2.5 +/- 2.7; p = .01) compared to CON. mRNA expression of VEGF-R2 and hypoxia
inducible factor 1alpha increased following BFR exercise but only eNOS were
enhanced relative to CON. Matrix metalloproteinase-9 mRNA expression was not
altered in response to either exercise. Acute low-load resistance exercise with
BFR provides a targeted angiogenic response potentially mediated through enhanced
ischaemic and shear stress stimuli.
PMID- 29343184
TI - Foot strike pattern in preschool children during running: sex and shod-unshod
differences.
AB - PURPOSE: This study aims to determine the foot strike patterns (FSPs) and neutral
support (no inversion [INV]/eversion [EVE] and no foot rotation) in preschool
children, as well as to determine the influence of shod/unshod conditions and
sex. METHODS: A total of 1356 children aged 3-6 years (673 boys and 683 girls)
participated in this study. A sagittal and frontal-plane video (240 Hz) was
recorded using a high-speed camcorder to record the following variables: rearfoot
strike (RFS), midfoot strike (MFS), forefoot strike (FFS), inversion/ eversion
(INV/EVE) and foot rotation on initial contact. RESULTS: There were no between
sex significant differences in both shod and unshod conditions in RFS. In the
unshod condition, there was a significant reduction (p < 0.001) of RFS prevalence
in both boys (shod condition = 44.2% vs. 34.7% unshod condition) and girls (shod
condition = 48.5% vs. 36.1% unshod condition). As for neutral support, there were
no between-sex differences in both shod and unshod conditions or in the shod
unshod comparison. CONCLUSION: In preschool children, no between-sex differences
were found in relation to prevalence of RFS and neutral support (no INV/EVE).
Shod running alters FSP of running barefoot, producing a significant increase of
RFS prevalence.
PMID- 29343185
TI - Exploring protein-protein intermolecular recognition between meprin-alpha and
endogenous protease regulator cystatinC coupled with pharmacophore elucidation.
AB - Meprins are a group of zinc metalloproteases of the astacin family which play a
pivotal role in several physiological and pathologocal diseases. The inhibition
of the meprins by various inhibitors, macromolecular and small molecules, is
crucial in the control of several diseases. Human cystatinC, an amyloidogenic
protein, is reported to be an endogenous inhibitor of meprin-alpha. In this
computational study, we elucidate a rational model for meprinalpha-cystatinC
complex using protein-protein docking. The complex model as well as the unbound
form was evaluated by molecular dynamics simulation. A simulation study revealed
higher stability of the complex owing to the presence of several interactions.
Virtual alanine mutagenesis helps in identifying the hotspots on both proteins.
Based on the frequency of occurrence of hotspot amino acids, it was possible to
enumerate the important amino acids primarily responsible for protein stability
present at the amino-terminal end of cystatin. Finally, pharmacophore elucidation
carried out based on the information obtained from a series of small molecular
inhibitors against meprin-alpha can be utilized in future for rational drug
design and therapy.
PMID- 29343186
TI - Association between palliative care and life-sustaining treatments for patients
with dementia: A nationwide 5-year cohort study.
AB - BACKGROUND: The association between palliative care and life-sustaining
treatments for patients with dementia is unclear in Asian countries. AIM: To
analyse the use of palliative care and its association with aggressive treatments
based on Taiwanese national data. DESIGN: A matched cohort study was conducted.
The association between intervention and outcome was evaluated using conditional
logistic regression analyses. SETTING/PARTICIPANTS: The source population
comprised 239,633 patients with dementia diagnosed between 2002 and 2013. We
selected patients who received palliative care between 2009 and 2013 (the
treatment cohort; N = 1996) and assembled a comparative cohort ( N = 3992)
through 1:2 matching for confounding factors. RESULTS: After 2009, palliative
care was provided to 3928 (1.64%) patients of the dementia population. The odds
ratio for undergoing life-sustaining treatments in the treatment cohort versus
the comparative cohort was <1 for most treatments (e.g. 0.41 for mechanical
ventilation (95% confidence interval: 0.35-0.48)). The odds ratio was >1 for some
treatments (e.g. 1.73 for tube feeding (95% confidence interval: 1.54-1.95)).
Palliative care was more consistently associated with fewer life-sustaining
treatments for those with cancer. CONCLUSIONS: Palliative care is related to
reduced life-sustaining treatments for patients with dementia. However, except in
the case of tube feeding, which tended to be provided alongside palliative care
regardless of cancer status, having cancer possibly had itself a protective
effect against the use of life-sustaining treatments. Modifying the eligibility
criteria for palliative care in dementia, improving awareness on the terminal
nature of dementia and facilitating advance planning for dementia patients may be
priorities for health policies.
PMID- 29343187
TI - Mechanical and antibacterial properties of benzothiazole-based dental resin
materials.
AB - A synthesized benzothiazole containing mono-methacrylate monomer BTTMA was
incorporated into Bis-GMA/TEGDMA dental resin system with a series of mass
concentration from 5 to 30 wt.% as an antibacterial agent. The influence of BTTMA
on physicochemical properties of dental resin system, such as double bond
conversion (DC), volumetric shrinkage (VS), flexural strength (FS) and modulus
(FM), water sorption (WS) and solubility (SL) were investigated. Direct contact
testing and agar diffusion testing were used to evaluate the antibacterial
activity of BTTMA containing dental resin. The results showed that BTTMA could
endow dental resin with significant antibacterial activity when its concentration
reached a certain amount (20 wt.%), and the antibacterial activity of BTTMA
containing dental resin was mainly attributed to the immobilized BTTMA instead of
the unreacted leachable BTTMA. BTTMA had no negative effect on physicochemical
properties of dental resin, and even some BTTMA containing dental resins had
advantages like higher DC, lower VS and WS when compared with control resin.
Therefore, BTTMA could be considered as a suitable antibacterial agent in dental
material, but much more researches concerned about biocompatibility should be
done in future to prove whether it could be applied in clinic.
PMID- 29343188
TI - Technique selection in young female gymnasts: Elbow and wrist joint loading
during the cartwheel and round-off.
AB - Biophysical loading of the elbow and wrist is a potential reason for chronic
lesions in gymnastics and present a real concern for coaches, scientist and
clinicians. Previous research has identified injury risk factors during round-off
(RO) skills in elite female gymnasts. The aim of this study was to investigate
key elbow and wrist joint injury risk factors during different techniques of
fundamental cartwheel (CW) and RO skills performed by young female artistic
gymnasts. Seventeen active young female gymnasts performed 30 successful trials
of both CW and RO from a hurdle step with three different hand positions
(parallel (10), T-shape (10) and reverse (10)). Synchronised kinematic (240 Hz)
and kinetic (1200 Hz) data were collected for each trial. One-way repeated
measures ANOVA and effect size (ES) were used for statistical analysis. The
results showed statistically significant differences (P < .05) and large ES
(>0.8) among hand positions for peak vertical ground reaction force (VGRF), peak
elbow compression force, peak wrist compression force, elbow internal adduction
moment and wrist dorsiflexion angle. In conclusion, the parallel and reverse
techniques increase peak VGRF, elbow and wrist compression forces, and elbow
internal adduction moment. These differences indicate that the parallel and
reverse techniques may increase the potential of elbow and wrist injuries in
young gymnasts compared with the T-shape technique; this is of particular
importance with the high frequency of the performance of these fundamental
skills.
PMID- 29343189
TI - Translating Ancient Alchemy: Fragments of Graeco-Egyptian Alchemy in Arabic
Compendia.
AB - Translation played a vital role in the development and transfer of alchemy in
Antiquity and the Early Middle Ages. Since its origins in Graeco-Roman Egypt,
alchemy was encapsulated in Greek texts which allegedly relied on Persian or
Egyptian sources. Later, a variety of Greek and Byzantine writings were
translated into Syriac and Arabic, and these translations were in turn fragmented
and disseminated in later Arabic compendia. This paper will first review the main
phases of this historical process of transmission of alchemy from one language
and culture to another. Second, this process will be examined using two
significant case studies: a close analysis of various quotations from Graeco
Egyptian authors (Pseudo-Democritus, Zosimus of Panopolis, and Synesius) as
presented in two Arabic dialogues on alchemy, The Tome of Images and The Dialogue
between Aras and the King Caesar. These sources demonstrate some of the concrete
textual realities that underlie general patterns of translation and reception.
PMID- 29343190
TI - Factors affecting effective ventilation during newborn resuscitation: a
qualitative study among midwives in rural Tanzania.
AB - BACKGROUND: Intrapartum-related hypoxia accounts for 30% of neonatal deaths in
Tanzania. This has led to the introduction and scaling-up of the Helping Babies
Breathe (HBB) programme, which is a simulation-based learning programme in
newborn resuscitation skills. Studies have documented ineffective ventilation of
non-breathing newborns and the inability to follow the HBB algorithm among
providers. OBJECTIVE: This study aimed at exploring barriers and facilitators to
effective bag mask ventilation, an essential component of the HBB algorithm,
during actual newborn resuscitation in rural Tanzania. METHODS: Eight midwives,
each with more than one year's working experience in the labour ward, were
interviewed individually at Haydom Lutheran Hospital, Tanzania. The audio
recordings were transcribed and translated into English and analysed using
qualitative content analysis. RESULTS: Midwives reported the ability to monitor
labour properly, preparing resuscitation equipment before delivery, teamwork and
frequent ventilation training as the most effective factors in improving actual
ventilation practices and promoting the survival of newborns. They thought that
their anxiety and fear due to stress of ventilating a non-breathing baby often
led to poor resuscitation performance. Additionally, they experienced
difficulties assessing the baby's condition and providing appropriate clinical
responses to initial interventions at birth; hence, further necessary actions and
timely initiation of ventilation were delayed. CONCLUSIONS: Efforts should be
focused on improving labour monitoring, birth preparedness and accurate
assessment immediately after birth, to decrease intrapartum-related hypoxia.
Midwives should be well prepared to treat a non-breathing baby through high
quality and frequent simulation training with an emphasis on teamwork training.
PMID- 29343191
TI - Thermophilic xylanases: from bench to bottle.
AB - Lignocellulosic biomass is a valuable raw material. As technology has evolved,
industrial interest in new ways to take advantage of this raw material has grown.
Biomass is treated with different microbial cells or enzymes under ideal
industrial conditions to produce the desired products. Xylanases are the key
enzymes that degrade the xylosidic linkages in the xylan backbone of the biomass,
and commercial enzymes are categorized into different glycoside hydrolase
families. Thermophilic microorganisms are excellent sources of industrially
relevant thermostable enzymes that can withstand the harsh conditions of
industrial processing. Thermostable xylanases display high-specific activity at
elevated temperatures and distinguish themselves in biochemical properties,
structures, and modes of action from their mesophilic counterparts. Natural
xylanases can be further improved through genetic engineering. Rapid progress
with genome editing, writing, and synthetic biological techniques have provided
unlimited potential to produce thermophilic xylanases in their natural hosts or
cell factories including bacteria, yeasts, and filamentous fungi. This review
will discuss the biotechnological potential of xylanases from thermophilic
microorganisms and the ways they are being optimized and produced for various
industrial applications.
PMID- 29343192
TI - Coverage and outcomes of antenatal tests for infections: a population based
survey in the Province of Trento, Italy.
AB - BACKGROUND: Rubella, syphilis, toxoplasmosis, cytomegalovirus (CMV), hepatitis B
(HBV) and C (HCV), HIV, and Group B Streptococcus (GBS) infections may have very
severe outcomes during pregnancy, and for this reason, monitoring of infections
in pregnant women is a requirement of prenatal assistance. AIMS: To describe
coverage and outcome of the screening for rubella, syphilis, toxoplasmosis, CMV,
HBV, HCV, HIV, and Group B Streptococcus in pregnancy in the Autonomous Province
of Trento, Northern Italy (538,600 inhabitants). METHODS: We analysed the
coverage and outcome of the above-mentioned screenings among women who delivered
in the hospitals of the Province of Trento between 2007 and 2014 (N = 38,712).
Screenings were grouped according to characteristics such as recommendation by
national and local guidelines, scheduling of the tests, operating methods, and
charge. We also estimated odds ratios (ORs) for missing screening for selected
infections through multiple logistic regression. RESULTS: Estimated uptake of
antenatal screening was 99.7% for rubella, 99.3% for syphilis, 99.7% for
toxoplasmosis, 98.1% for HIV infection, 99.0% for HBV, 98.9% for HCV, 94.0% for
GBS infection, and 75.4% for CMV infection. The overall prevalence of immunity
was 94.1% for rubella, 24.2% for toxoplasmosis, and 64.2% for CMV. The rate of
seroconversion in pregnant women was 0.02% for rubella, 0.29% for toxoplasmosis,
and 0.75% for CMV. The overall prevalence of infection was 0.94% for HBV, 0.53%
for HCV, 22.3% for GBS, 0.29% for syphilis, and 0.13% for HIV. We found a
significant positive association for all screening tests, between lack of testing
and late first medical examination in pregnancy (ORs ranging from 1.20 to 1.66
for the first medical visit in the second trimester and ORs ranging from 1.60 to
5.88 for the first medical visit in third trimester, compared to early medical
visit in the first trimester). Compared to Italian citizenship, foreign
citizenship of the mother was also positively associated with absence of
screening (ORs ranging from 1.30 to 1.53). A significant inverse association was
observed for calendar year of delivery (ORs ranging from 0.71 to 0.97, for 1 year
increment). Less educated mothers and pluriparae were also at higher risks of not
being tested. Analysis of the association with mother age showed different
heterogeneous effects. CONCLUSIONS: Our study indicates that the attention to
screening and detecting infected cases is growing over the time. In addition,
care delivered during pregnancy has a leading role in determining coverage of the
examinations. Immigrant, pluriparous and less educated women need particular
attention.
PMID- 29343193
TI - Perinatal sclerostin concentrations in abnormal fetal growth: the impact of
gestational diabetes.
AB - OBJECTIVE: To prospectively evaluate maternal and cord blood concentrations of
sclerostin - an osteocyte-secreted factor, inhibiting osteoblast differentiation
and bone formation and associated with adverse metabolism - in pregnancies with
normal and abnormal fetal growth. METHODS: Plasma sclerostin concentrations were
determined by ELISA in 80 maternal and 80 cord blood samples from asymmetric
intrauterine-growth-restricted (IUGR, n = 30), large-for-gestational-age (LGA, n
= 30), and appropriate-for-gestational-age (AGA, n = 20) singleton full-term
pregnancies. Fourteen out of 30 mothers with LGA offspring presented with
gestational diabetes mellitus (GDM). RESULTS: Maternal and fetal sclerostin
concentrations did not differ among LGA, IUGR, and AGA groups. Fetal
concentrations were higher than maternal. In LGA group, maternal concentrations
were elevated in cases of GDM (b = 13.009, 95%CI 1.425-24.593, p = .029). In a
combined group and the IUGR group, maternal concentrations were elevated in older
mothers (b = 0.788, 95%CI 0.190-1.385, p = .010, and b = 0.740, 95%CI 0.042
1.438, p = .039, respectively). CONCLUSIONS: Maternal and fetal sclerostin
concentrations may not be differentially regulated in pregnancies complicated by
abnormal fetal growth. Circulating maternal levels are higher in cases of GDM,
probably implying reduced bone formation. Sclerostin up-regulation with aging may
be one of the molecular pathways responsible for the observed age-related decline
in bone synthesis, leading to accelerated bone loss in humans.
PMID- 29343194
TI - A brain impact stress analysis using advanced discretization meshless techniques.
AB - This work has the objective to compare the mechanical behaviour of a brain impact
using an alternative numerical meshless technique. Thus, a discrete geometrical
model of a brain was constructed using medical images. This technique allows to
achieve a discretization with realistic geometry, allowing to define locally the
mechanical properties according to the medical images colour scale. After
defining the discrete geometrical model of the brain, the essential and natural
boundary conditions were imposed to reproduce a sudden impact force. The analysis
was performed using the finite element analysis and the radial point
interpolation method, an advanced discretization technique. The results of both
techniques are compared. When compared with the finite element analysis, it was
verified that meshless methods possess a higher convergence rate and that they
are capable of producing smoother variable fields.
PMID- 29343195
TI - Caring for a family member or friend with dementia at the end of life: A scoping
review and implications for palliative care practice.
AB - BACKGROUND: Although people with dementia receive substantial care from informal
sources, there is limited research available that investigates how these carers
experience end-of-life care. AIM: This review aimed to identify what is currently
known about carers' experiences of providing end-of-life care to a family member
or friend with dementia and draw implications for palliative care policy and
service provision. DESIGN: A scoping literature review was conducted, first using
a targeted key word search, followed by assessments of eligibility based on title
and then abstract content. DATA SOURCES: Records were sourced through PsycINFO,
PubMed and CINAHL databases. Peer-reviewed papers published between 2000 and
2016, reporting on data collected directly from carers, were included for review.
RESULTS: Carers' experience centred on relationships (with care recipients,
family and friends and health care professionals) and the specific context of
caring for someone with dementia. These broad categories of carers' experiences
had clear influences on them personally, particularly in relation to their sense
of self and their wellbeing. CONCLUSION: Palliative care services would benefit
from ensuring holistic approaches to supporting people with dementia, their
carers and wider family networks. Tailoring services to the specific context of
dementia would enable effective, personalised support throughout extended periods
leading up to care recipient death as well as through the challenges faced beyond
bereavement.
PMID- 29343196
TI - Plexiform Vasculopathy in Feline Cervical Lymph Nodes.
AB - Plexiform vasculopathy refers to an endothelial proliferative disorder affecting
cervical or inguinal lymph nodes of cats. The cause of this disorder and the
origin of the proliferating endothelial cells are still unknown. In 4 cats with a
history of a slowly growing, well-demarcated, nonpainful mass adjacent to the
thyroid gland, an enlarged dark brown to red lymph node was removed.
Histologically, the lymph nodes showed severe loss of lymphoid tissue with
accumulations of erythrocytes. In addition, networks of capillary structures with
well-differentiated endothelial cells on a collagen-rich stroma were observed,
consistent with benign plexiform vasculopathy. Immunohistochemistry revealed the
expression of the vascular endothelial markers CD31 and factor VIII-related
antigen. In addition, immunolabeling with a Prox-1 antibody indicated a
lymphendothelial origin. With respect to our findings, a lymphendothelial origin
has to be considered in cases of intranodal vascular neoplasms.
PMID- 29343197
TI - Coexpression of CD3 and CD20 in Canine Enteropathy-Associated T-cell Lymphoma.
AB - The majority of primary intestinal lymphomas in dogs are T-cell lymphomas, with
enteropathy-associated T-cell lymphoma (EATL) large cell type (type 1) being the
most common. While most T-cell lymphomas express the T-cell marker CD3, there is
increasing evidence that some human and canine T-cell lymphomas coexpress the B
cell marker CD20. We describe 3 cases of CD3+, CD20+, Pax5- EATL type 1 in dogs.
All 3 cases had clonal rearrangement of T-cell receptor gamma. Initial clinical
signs included weight loss, inappetence, diarrhea, and/or vomiting. The mean age
was 9 years (range 3-12). Survival was highly variable ranging from 20 days to
longer than 1.6 years. Considering the different chemotherapeutic response of T
cell versus B-cell lymphomas, accurate diagnosis of lymphomas coexpressing CD3
and CD20 as EATL type 1 based on histologic features and clonality results is
important. Regardless, the clinical and/or prognostic significance of neoplastic
T cells expressing CD20 is unclear.
PMID- 29343198
TI - Localization of Felis catus Papillomavirus Type 2 E6 and E7 RNA in Feline
Cutaneous Squamous Cell Carcinoma.
AB - Findings from polymerase chain reaction-based methods have suggested a role of
Felis catus papillomavirus 2 (FcaPV-2) in the development of feline cutaneous
squamous cell carcinoma (SCC). However, because polymerase chain reaction cannot
localize deoxyribonucleic acid or ribonucleic acid within the lesion, it is
difficult to differentiate a coincidental FcaPV-2 infection and a causative
association. Given that a key event in the pathogenesis of human papillomavirus
induced cancer is the expression of viral E6 and E7 oncogenes, localization of
FcaPV-2 E6 and E7 transcription within neoplastic cells in feline SCCs would
support a causative role for this papillomavirus. Therefore, RNAscope in situ
hybridization was used to localize FcaPV-2 E6 and E7 transcripts in 18 formalin
fixed paraffin-embedded samples of cutaneous SCC. Positive signals were present
within 5 of 9 samples (56%) from ultraviolet-protected sites and 0 of 9 samples
from ultraviolet-exposed sites. In the 4 in situ hybridization-positive samples
that contained adjacent hyperplastic skin, hybridization patterns in these
regions were characterized by intense nuclear signals within the superficial
epidermis and punctate signals within the basal epithelial layers. However,
within the 5 SCCs, punctate signals were present within all layers of the
epidermis, with progressive loss of intense nuclear signals within the
superficial epidermis. This hybridization pattern is consistent with unregulated
E6 and E7 transcription and decreased viral replication and is similar to the
pattern observed in human papillomavirus-induced cancers as they progress from
hyperplastic lesions containing productive infections to nonproductive neoplasms.
These findings support a causative role for FcaPV-2 in the pathogenesis of feline
SCC.
PMID- 29343199
TI - CD204-Expressing Tumor-Associated Macrophages Are Associated With Malignant, High
Grade, and Hormone Receptor-Negative Canine Mammary Gland Tumors.
AB - Tumor-associated macrophages (TAMs) are an important component of leukocyte
infiltration in tumors. TAMs can be classified into M1 and M2 phenotypes. In the
present study, the expression of CD204, an M2-polarized macrophage receptor, was
investigated by immunohistochemistry in the area surrounding TAMs in 101 cases of
canine mammary gland tumor (CMT). We examined the relationship between M2
polarized TAMs and malignancy, histological subtype, histological grade,
molecular subtype, hormone receptor (HR) status, and clinical obesity indices.
The mean number of CD204-positive macrophages was significantly higher in
malignant CMTs than in benign CMTs ( P = .000). The number of CD204-positive
macrophages differed significantly between histological grades ( P = .000) and
were significantly higher in grade III than in grades I and II. Moreover, the
mean number of CD204-positive macrophages was significantly higher in HR-negative
malignant CMTs than in HR-positive malignant CMTs ( P = .035) and in malignant
CMTs with lymphatic invasion compared to malignant CMTs without lymphatic
invasion ( P = .000). These findings suggest that CD204-positive macrophages
might affect the development and behavior of CMTs and highlight the potential of
CD204 as a prognostic factor.
PMID- 29343200
TI - Immunohistochemical Expression of CD31 (PECAM-1) in Nonendothelial Tumors of
Dogs.
AB - CD31 immunoreactivity has been reported in human nonendothelial tumors of both
epithelial and mesenchymal origin. This study examined CD31 immunoreactivity of
347 formalin-fixed, paraffin-embedded normal, nonneoplastic, and neoplastic
canine tissues. CD31 expression was considered positive if at least 10% of the
cell population had membranous reactivity. Labeling with the CD31 antibody (clone
JC/70A) was observed in 16 samples of normal organs (liver, kidney, lymph node),
6 of 6 specimens of hepatic nodular hyperplasia, 3 of 3 hepatic regenerative
nodules, 1 of 4 anal sac carcinomas, 6 of 6 hemangiosarcomas, 18 of 20
hepatocellular carcinomas, 1 of 6 mammary carcinomas, 3 of 5 plasmacytomas, 18 of
53 renal cell carcinomas, and 1 of 5 cutaneous histiocytomas. CD31 expression did
not correlate with case outcome in hepatocellular or renal cell carcinomas.
Although distinguishing hemangiosarcoma from other neoplasms is typically
straightforward, pathologists should be aware of potential cross-reactivity when
relying on CD31 immunohistochemistry for diagnosis, particularly in small biopsy
samples or when faced with an epithelioid or poorly differentiated vascular
neoplasm.
PMID- 29343201
TI - The impact of blackcurrant juice on attention, mood and brain wave spectral
activity in young healthy volunteers.
AB - There is a growing body of evidence from randomized controlled trials which
indicates that consumption of berries has a positive effect upon the cognitive
function of healthy adults. It has been recommended that studies combining
cognitive and physiological measures be undertaken in order to strengthen the
evidence base for the putative effects of flavonoid consumption on cognitive
outcomes. This pilot study utilized a randomized, double-blind and placebo
controlled crossover design to assess the influence of the acute administration
of anthocyanin-rich blackcurrant juice, standardized at 500 mg of polyphenols, on
mood and attention. Additionally, this trial used electroencephalography (EEG) to
assess if any changes in cognitive performance are associated with changes in
localized prefrontal cortex neuronal activity in nine healthy young adults.
Outcomes from the pilot EEG data highlight an anxiolytic effect of the
consumption of a single serve blackcurrant juice, as indexed by a suppression of
alpha spectral power, and an increase in the slow wave delta and theta spectral
powers. There was also an indication of greater alertness and lower fatigue, as
indexed by an increase in beta power and suppression of alpha spectral power.
Outcomes from the CogTrackTM system indicated a small acute increase in reaction
times during the digit vigilance task.
PMID- 29343202
TI - Pillars of wisdom: ankylosing spondylitis in pocket format from the master.
PMID- 29343203
TI - Cognition, Health-Related Quality of Life, and Depression Ten Years after
Moderate to Severe Traumatic Brain Injury: A Prospective Cohort Study.
AB - The aim of this study was to evaluate cognitive function 10 years after moderate
severe traumatic brain injury (TBI) and to investigate the associations among
cognitive function, depression, and health-related quality of life (HRQoL). In
this prospective cohort study, with measurements at 3, 6, 12, 18, 24, 36, and 120
months post-TBI, patients 18-67 years of age (n = 113) with moderate-severe TBI
were recruited. Main outcome measures were depression (Center for Epidemiologic
Studies-Depression Scale [CES-D]), subjective cognitive functioning (Cognitive
Failure Questionnaire [CFQ]), objective cognitive functioning, and HRQoL (Medical
Outcomes Study 36-Item Short Form Health Survey [SF-36]). Fifty of the initial
113 patients completed the 10 year follow-up. Twenty percent showed symptoms of
depression (CES-D >= 16). These patients had more psychiatric symptoms at
hospital discharge (p = 0.048) and were more often referred to rehabilitation or
nursing homes (p = 0.015) than non-depressed patients. Further, they also had
significantly lower scores in six of the eight subdomains of the SF-36. The non
depressed patients had equivalent scores to those of the Dutch norm-population on
all subdomains of the SF-36. Cognitive problems at hospital discharge were
related with worse cognitive outcome 10 years post-TBI, but not with depression
or HRQoL. Ten years after moderate-severe TBI, only weak associations (p < 0.05)
between depression scores and two objective cognitive functioning scores were
found. However, there were moderate associations (p < 0.01) among depression
scores, HRQoL, and subjective cognitive functioning. Therefore, signaling and
treatment of depressive symptoms after moderate-severe TBI may be of major
importance for optimizing HRQoL in the long term. We did not find strong evidence
for associations between depression and objective cognitive functioning in the
long term post-TBI. Disease awareness and selective dropping out may play a role
in long-term follow-up studies in moderate-severe TBI. More long-term research is
needed in this field.
PMID- 29343204
TI - Automatic Intracranial Segmentation: Is the Clinician Still Needed?
AB - INTRODUCTION: Stereotactic hypofractionated radiotherapy is an effective
treatment for brain metastases in oligometastatic patients. Its planning is
however time-consuming because of the number of organs at risk to be manually
segmented. This study evaluates 2 automated segmentation commercial software.
METHODS: Patients were scanned in the treatment position. The computed tomography
scan was registered on a magnetic resonance imaging and volumes were manually
segmented by a clinician. Then 2 automated segmentations were performed (with
iPlan and Smart Segmentation). RT STRUCT files were compared with Aquilab's
Artistruct segment comparison module. We selected common segmented volume ratio
as the main judging criterion. Secondary criteria were Dice-Sorensen
coefficients, overlap ratio, and additional segmented volume. RESULTS: Twenty
consecutive patients were included. Agreement between manual and automated
contouring was poor. Common segmented volumes ranged from 7.71% to 82.54%, Dice
Sorensen coefficient ranged from 0.0745 to 0.8398, overlap ratio ranged from
0.0414 to 0.7275, and additional segmented volume ranged from 9.80% to 92.25%.
Each software outperformed the other on some organs while performing worse on
others. CONCLUSION: No software seemed clearly better than the other. Common
segmented volumes were much too low for routine use in stereotactic
hypofractionated brain radiotherapy. Manual editing is still needed.
PMID- 29343205
TI - A Network Meta-Analysis on the Diagnostic Value of Different Imaging Methods for
Lymph Node Metastases in Patients With Cervical Cancer.
AB - PURPOSE: We performed this network meta-analysis to compare the diagnostic value
of 4 imaging methods (magnetic resonance imaging, positron emission tomography,
computed tomography, and diffusion-weighted imaging) for diagnosing lymph node
metastases in cervical cancer. METHOD: Diagnostic tests regarding different
imaging methods to diagnose lymph node metastases in cervical cancer were
retrieved from the Cochrane Library, PubMed, and Embase electronic databases from
inception to December 2016. Direct and indirect evidence was performed to
calculate the odds ratio and to draw the surface under the cumulative ranking
curves of the 4 imaging methods for diagnosing lymph node metastases in cervical
cancer. RESULTS: Sixteen eligible diagnostic tests were included in this network
meta-analysis. The results of network meta-analysis demonstrate that in
comparison with the diffusion-weighted imaging, positive likelihood ratio,
negative likelihood ratio, and diagnostic odds ratio of positron emission
tomography were relatively higher. Additionally, the results further indicate
that compared with other diagnosis method, positive likelihood ratio, negative
likelihood ratio, and diagnostic odds ratio of positron emission tomography had a
higher trend. The surface under the cumulative ranking curve results indicated
that in terms of positive likelihood ratio and diagnostic odds ratio, positron
emission tomography had a relatively higher diagnostic value for lymph node
metastases in patients with cervical cancer. CONCLUSION: Our findings indicate
that positron emission tomography might have a relatively higher diagnostic value
for lymph node metastases in patients with cervical cancer.
PMID- 29343206
TI - Line-Enhanced Deformable Registration of Pulmonary Computed Tomography Images
Before and After Radiation Therapy With Radiation-Induced Fibrosis.
AB - PURPOSE: The deformable registration of pulmonary computed tomography images
before and after radiation therapy is challenging due to anatomic changes from
radiation fibrosis. We hypothesize that a line-enhanced registration algorithm
can reduce landmark error over the entire lung, including the irradiated regions,
when compared to an intensity-based deformable registration algorithm. MATERIALS:
Two intensity-based B-spline deformable registration algorithms of pre-radiation
therapy and post-radiation therapy images were compared. The first was a control
intensity-based algorithm that utilized computed tomography images without
modification. The second was a line enhancement algorithm that incorporated a
Hessian-based line enhancement filter prior to deformable image registration.
Registrations were evaluated based on the landmark error between user-identified
landmark pairs and the overlap ratio. RESULTS: Twenty-one patients with pre
radiation therapy and post-radiation therapy scans were included. The median time
interval between scans was 1.2 years (range: 0.3-3.3 years). Median landmark
errors for the line enhancement algorithm were significantly lower than those for
the control algorithm over the entire lung (1.67 vs 1.83 mm; P < .01), as well as
within the 0 to 5 Gy (1.40 vs 1.57; P < .01) and >5 Gy (2.25 vs 3.31; P < .01)
dose intervals. The median lung mask overlap ratio for the line enhancement
algorithm (96.2%) was greater than that for the control algorithm (95.8%; P <
.01). Landmark error within the >5 Gy dose interval demonstrated a significant
inverse relationship with post-radiation therapy fibrosis enhancement after line
enhancement filtration (Pearson correlation coefficient = -0.48; P = .03).
CONCLUSION: The line enhancement registration algorithm is a promising method for
registering images before and after radiation therapy.
PMID- 29343207
TI - Genome-Wide Analysis Identified a Number of Dysregulated Long Noncoding RNA
(lncRNA) in Human Pancreatic Ductal Adenocarcinoma.
AB - BACKGROUND: Long noncoding RNAs have been shown to play crucial roles in cancer
biology, while the long noncoding RNA landscapes of pancreatic ductal
adenocarcinoma have not been completely characterized. We aimed to determine
whether long noncoding RNA could serve as early diagnostic biomarkers for
pancreatic ductal adenocarcinoma. METHOD: We conducted a genome-wide microarray
analysis on pancreatic ductal adenocarcinoma and their adjacent noncancerous
tissues from 8 Chinese patients. RESULTS: A total of 3352 significantly
differentially expressed long noncoding RNAs were detected. Of total, 1249 long
noncoding RNAs were upregulated and 2103 were downregulated (fold change >=2, P <
0.05, FDR <0.05). These differentially expressed long noncoding RNAs were not
evenly distributed among chromosomes in human genome. Hierarchical clustering of
these differentially expressed long noncoding RNAs revealed large variabilities
in long noncoding RNA expression among individual patient, indicating that
certain long noncoding RNAs could play a unique role or be used as a biomarker
for specific subtype of pancreatic ductal adenocarcinoma. Gene Ontology
enrichment and pathway analysis identified several remarkably dysregulated
pathways in pancreatic ductal adenocarcinoma tissue, such as interferon-gamma
mediated signaling pathway, mitotic cell cycle and proliferation, extracellular
matrix receptor interaction, focal adhesion, and regulation of actin
cytoskeleton. The co-expression network analysis detected 393 potential
interactions between 80 differentially expressed long noncoding RNAs and 105
messenger RNAs. We experimentally verified 7 most markedly dysregulated long
noncoding RNAs from the network. CONCLUSION: Our study provided a genome-wide
survey of dysregulated long noncoding RNAs and long noncoding RNA/messenger RNA
co-regulation networks in pancreatic ductal adenocarcinoma tissue. These
dysregulated long noncoding RNA/messenger RNA networks could be used as
biomarkers to provide early diagnosis of pancreatic ductal adenocarcinoma or its
subtype, predict prognosis, and evaluate treatment efficacy.
PMID- 29343208
TI - Lapatinib Inhibits Breast Cancer Cell Proliferation by Influencing PKM2
Expression.
AB - Pyruvate kinase type M2, which is expressed in multiple tumor cell types and
plays a key role in aerobic glycolysis, also has nonglycolytic functions and can
regulate transcription and cell proliferation. The results of this study show
that epidermal growth factor receptor activation induces pyruvate kinase type M2
nuclear translocation. To further determine the relationship between pyruvate
kinase type M2 and epidermal growth factor receptor, we analyzed pathological
data from mammary glands and performed epidermal growth factor receptor/human
epidermal growth factor receptor 2 knockdown to reveal that pyruvate kinase type
M2 is associated with epidermal growth factor receptor and human epidermal growth
factor receptor 2. Lapatinib is a small molecule epidermal growth factor receptor
tyrosine kinase inhibitor that can inhibit epidermal growth factor receptor and
human epidermal growth factor receptor 2, though its effect on pyruvate kinase
type M2 remains elusive. Accordingly, we performed Western blotting and reverse
transcription polymerase chain reaction and analyzed pathological data from
mammary glands, with results suggesting that lapatinib inhibits pyruvate kinase
type M2 expression. We further found that the antitumor drug lapatinib inhibits
breast cancer cell proliferation by influencing pyruvate kinase type M2
expression, as based on Cell Counting Kit-8 analyses and pyruvate kinase type M2
overexpression experiments. Signal transducer and activator of transcription 3,
which is a transcription factor-associated cell proliferation and the only
transcription factor that interacts with pyruvate kinase type M2, we performed
pyruvate kinase type M2 knockdown experiments in Human breast cancer cells MDA-MB
231 and Human breast cancer cells SK-BR-3 cell lines and examined the effect on
levels of Signal transducer and activator of transcription 3 and phosphorylated
Signal transducer and activator of transcription 3. The results indicate that
pyruvate kinase type M2 regulates Signal transducer and activator of
transcription 3 and phospho-Stat3 (Tyr705) expression. Together with previous
reports, our findings show that lapatinib inhibits breast cancer cell
proliferation by influencing pyruvate kinase type M2 expression, which results in
a reduction in both Signal transducer and activator of transcription 3 and
phosphorylated Signal transducer and activator of transcription 3.
PMID- 29343210
TI - Prediction of structural consequences for disease causing variants in C21orf2
protein using computational approaches.
AB - Amyotrophic lateral sclerosis (ALS), a progressive motor-neurone disease, affects
individuals usually aged between 50 and 70 years. C21orf2, recently identified as
the new ALS susceptibility gene, harbours rare missense mutations that cause this
fatal disease. We used bioinformatics and molecular modelling approaches to study
specific ALS-associated mutations in C21orf2. Both native and mutant structures
of the protein obtained from homology modelling were analysed in detail to gain
insights into the potential impact of these mutations on the protein structure
and its function. Our analyses reveal that more than 75% of the mutations are
likely to be deleterious. These effects seem to carry through to mouse C21orf2 as
well, indicating that mouse would make a viable animal model to study this ALS
gene in detail.
PMID- 29343209
TI - Mild Blast Injury Produces Acute Changes in Basal Intracellular Calcium Levels
and Activity Patterns in Mouse Hippocampal Neurons.
AB - Mild traumatic brain injury (mTBI) represents a serious public health concern.
Although much is understood about long-term changes in cell signaling and
anatomical pathologies associated with mTBI, little is known about acute changes
in neuronal function. Using large scale Ca2+ imaging in vivo, we characterized
the intracellular Ca2+ dynamics in thousands of individual hippocampal neurons
using a repetitive mild blast injury model in which blasts were directed onto the
cranium of unanesthetized mice on two consecutive days. Immediately following
each blast event, neurons exhibited two types of changes in Ca2+ dynamics at
different time scales. One was a reduction in slow Ca2+ dynamics that
corresponded to shifts in basal intracellular Ca2+ levels at a time scale of
minutes, suggesting a disruption of biochemical signaling. The second was a
reduction in the rates of fast transient Ca2+ fluctuations at the sub-second time
scale, which are known to be closely linked to neural activity. Interestingly,
the blast-induced changes in basal Ca2+ levels were independent of the changes in
the rates of fast Ca2+ transients, suggesting that blasts had heterogeneous
effects on different cell populations. Both types of changes recovered after ~1
h. Together, our results demonstrate that mTBI induced acute, heterogeneous
changes in neuronal function, altering intracellular Ca2+ dynamics across
different time scales, which may contribute to the initiation of longer-term
pathologies.
PMID- 29343211
TI - PAX6 Alternative Splicing and Corneal Development.
AB - Paired box protein 6 (PAX6) is a master regulator of the eye development. Over
the last past two decades, our understanding of eye development, especially the
molecular function of PAX6, has focused on transcriptional control of the Pax6
expression. However, other regulatory mechanisms for gene expression, including
alternative splicing (AS), have been understudied in the eye development. Recent
findings suggest that two PAX6 isoforms generated by AS of Pax6 pre-mRNA may play
previously underappreciated role(s) during eye development, especially, the
corneal development.
PMID- 29343212
TI - Clinical Characteristics of Subtypes of Follicular Variant Papillary Thyroid
Carcinoma.
AB - BACKGROUND: Among follicular variant papillary thyroid carcinomas (FVPTCs), the
noninvasive encapsulated subtype has an excellent prognosis. For this reason,
reclassification of noninvasive encapsulated FVPTC (EFVPTC) as a new entity
called "noninvasive follicular thyroid neoplasm with papillary-like nuclear
features" (NIFTP) has been proposed, but controversy remains. To characterize
noninvasive EFVPTC in an Asian population, the clinicopathologic features of each
FVPTC subtype were compared in a Korean population. METHODS: FVPTC patients (n =
142) who underwent thyroidectomy between 2009 and 2014, and whose tumor size was
>1 cm, were included in the study. The surgical pathology of each patient was
reevaluated by two independent expert pathologists. RESULTS: The percentages of
noninvasive and invasive EFVPTC and infiltrative FVPTC (IFVPTC) in the study were
30%, 31%, and 39%, respectively. There was no difference in preoperative
cytological diagnosis or the extent of surgery between noninvasive and invasive
EFVPTC. However, the proportion of Bethesda category IV was lower in IFVPTC (16%)
than in noninvasive and invasive EFVPTC (35% and 36%, respectively). Therefore,
thyroid lobectomy was more common in noninvasive or invasive EFVPTC (54% or 48%,
respectively) than in IFVPTC (16%). Noninvasive EFVPTC showed lower multiplicity,
extrathyroidal extension, and BRAFV600E mutation frequency (three cases; 8%) than
did invasive EFVPTC, but other pathological characteristics were similar.
However, IFVPTC showed significant differences in tumor size, extrathyroidal
extension, lymph node metastasis, Tumor Node Metastasis stage, and American
Thyroid Association high-risk category compared with noninvasive and invasive
EFVPTC. In the noninvasive EFVPTC group, there were six (14%) cases with
multifocality and three (7%) cases with lymph node metastasis. However, only two
cases with multifocality and one case with lymph node metastasis originated from
noninvasive FVPTC, while the other cases were from coexisting conventional PTCs.
CONCLUSIONS: Noninvasive EFVPTC has favorable pathological features, but lymph
node metastasis or BRAFV600E mutations were observed in some patients. Therefore,
in order for the distinction between noninvasive EFVPTC and invasive EFVPTC to
have more clinical significance, the criteria for NIFTP need to be more strictly
revised.
PMID- 29343213
TI - The community is just a small circle: citizen participation in the free maternal
and child healthcare programme of Enugu State, Nigeria.
AB - BACKGROUND: There is a gap in knowledge about how citizen participation impacts
governance of free healthcare policies for universal health coverage in low- and
middle-income countries. OBJECTIVE: This study provides evidence about how social
accountability initiatives influenced revenue generation, pooling and fund
management, purchasing and capacity of health facilities implementing the free
maternal and child healthcare programme (FMCHP) in Enugu State, Nigeria. METHODS:
The study adopted a descriptive, qualitative case-study design to explore how
social accountability influenced implementation of the FMCHP at the state level
and in two health districts (Isi-Uzo and Enugu Metropolis) in Enugu State. Data
were collected from policymakers (n = 16), providers (n = 16) and health facility
committee leaders (n = 12) through in-depth interviews. We also conducted focus
group discussions (n = 4) with 42 service users and document review. Data were
analysed using thematic analysis. RESULTS: It was found that health facility
committees (HFCs) have not been involved in the generation of funds, fund
management and tracking of spending in FMCHP. The HFCs did not also seem to have
increased transparency of benefits and payment of providers. The HFCs emerged as
the dominant social accountability initiative in FMCHP but lacked power in the
governance of free health services. The HFCs were constrained by weak legal
framework, ineffectual FMCHP committees at the state and district levels,
restricted financial information disclosure, distrustful relationships with
policymakers and providers, weak patient complaint system and low use of service
charter. CONCLUSION: The HFCs have not played a significant role in health
financing and service provision in FMCHP. The gaps in HFCs' participation in
health financing functions and service delivery need to be considered in the
design and implementation of free maternal and child healthcare policies that aim
to achieve universal health coverage.
PMID- 29343214
TI - Establishing a genetic link between FTO and VDR gene polymorphisms and obesity in
the Emirati population.
AB - BACKGROUND: Obesity is a metabolic disease that is widely prevalent with
approximately 600 million people classified as obese worldwide. Its etiology is
multifactorial and involves a complex interplay between genes and the
environment. Over the past few decades, obesity rates among the Emirati
population have been increasing. The aim of this study was to investigate the
association of candidate gene single nucleotide polymorphisms (SNPs), namely FTO
(rs9939609) and VDR (rs1544410), with obesity in the UAE population. METHODS:
This is a case-control study in which genomic DNA was extracted from saliva
samples of 201 obese, 115 overweight, and 98 normal subjects in the United Arab
Emirates (UAE). Genotyping for the variants was performed using TaqMan assay.
RESULTS: The mean Body Mass Index (BMI) +/- SD for the obese, overweight, and
normal subjects was 35.76 +/- 4.54, 27.53 +/- 1.45, and 22.69 +/- 1.84 kg/m2,
respectively. Increasing BMI values were associated with increase in values of
HbA1c, systolic and diastolic blood pressure. There was a significant association
observed between the FTO SNP rs9939609 and BMI (p = 0.028), with the minor allele
A having a clear additive effect on BMI values. There was no significant
association detected between BMI and rs1544410 of VDR. Moreover, significant
interaction between the FTO rs9939609 and physical activity reduced the "AA"
genotype effect on increase in BMI (p = 0.027). CONCLUSIONS: Our study findings
indicate that the minor allele A of the rs9939609 has a significant association
with increasing BMI values. Moreover, our findings support the fact that
increasing BMI is associated with increasing risks of other comorbidities such as
higher blood pressure, poorer glycemic control, and higher triglycerides. In
addition, physical activity was found to attenuate the effect of the "AA"
genotype on the predisposition to higher BMI values.
PMID- 29343215
TI - Women's decision-making processes and the influences on their mode of birth
following a previous caesarean section in Taiwan: a qualitative study.
AB - BACKGROUND: Vaginal birth after caesarean (VBAC) is an alternative option for
women who have had a previous caesarean section (CS); however, uptake is limited
because of concern about the risks of uterine rupture. The aim of this study was
to explore women's decision-making processes and the influences on their mode of
birth following a previous CS. METHODS: A qualitative approach was used. The
research comprised three stages. Stage I consisted of naturalistic observation at
33-34 weeks' gestation. Stage II involved interviews with pregnant women at 35-37
weeks' gestation. Stage III consisted of interviews with the same women who were
interviewed postnatally, 1 month after birth. The research was conducted in a
private medical centre in northern Taiwan. Using a purposive sampling, 21 women
and 9 obstetricians were recruited. Data collection involved in-depth interviews,
observation and field notes. Constant comparative analysis was employed for data
analysis. RESULTS: Ensuring the safety of mother and baby was the focus of
women's decisions. Women's decisions-making influences included previous birth
experience, concern about the risks of vaginal birth, evaluation of mode of
birth, current pregnancy situation, information resources and health insurance.
In communicating with obstetricians, some women complied with obstetricians'
recommendations for repeat caesarean section (RCS) without being informed of
alternatives. Others used four step decision-making processes that included
searching for information, listening to obstetricians' professional judgement,
evaluating alternatives, and making a decision regarding mode of birth. After
birth, women reflected on their decisions in three aspects: reflection on birth
choices; reflection on factors influencing decisions; and reflection on outcomes
of decisions. CONCLUSIONS: The health and wellbeing of mother and baby were the
major concerns for women. In response to the decision-making influences, women's
interactions with obstetricians regarding birth choices varied from passive
decision-making to shared decision-making. All women have the right to be
informed of alternative birthing options. Routine provision of explanations by
obstetricians regarding risks associated with alternative birth options, in
addition to financial coverage for RCS from National Health Insurance, would
assist women's decision-making. Establishment of a website to provide women with
reliable information about birthing options may also assist women's decision
making.
PMID- 29343216
TI - An appraisal: how notifiable infectious diseases are reported by Hungarian family
physicians.
AB - BACKGROUND: Within the frame of National Epidemiological Surveillance System,
family physicians have an obligation to report infections and suspicions cases.
The aim of this study was to evaluate the knowledge, attitudes, daily practice
and the reporting activities of Hungarian family physicians regarding to
infectious diseases. METHODS: A self-administered survey was developed, validated
and used. The survey was completed by family physicians who had taken part in
continuous medical educational programmes of all Hungarian medical faculties. The
questionnaire, consisting demographic questions and 10 statements about their
reporting habits were completed by 347 doctors, 8% of the total number of family
physicians. The data were processed in a cross-sectional design with general
linear model. RESULTS: According to the majority of responders, the current
reporting system works efficiently. Rural physicians were mainly agreed, that
reporting is not a simply obligation, it is a professional task as well. They
were less hindered in daily work by reporting activities, waited less for
laboratory confirmation before reporting, reported suspicious cases more
frequently. Practitioner's based in urban settlements preferred to await
laboratory tests before reporting and were hindered less by failures of the
electronic reporting system. Older physicians trusted more in the recent system
and they wished to increase the number of reports. Female physicians have higher
consciousness in epidemiology. They were mostly in agreement that even severe
infectious diseases can be diagnosed at primary care level and their daily
practices were less burdened by reporting duties. CONCLUSIONS: Both the
epidemiological knowledge of general practitioners' and the electronic
surveillance systems should be improved. There is a need to develope the
electronic infrastructure of primary care. More and regular control is also
expected by the health care authorities, beside the synthesis of professional and
governmental expectations and regulations.
PMID- 29343218
TI - LocText: relation extraction of protein localizations to assist database
curation.
AB - BACKGROUND: The subcellular localization of a protein is an important aspect of
its function. However, the experimental annotation of locations is not even
complete for well-studied model organisms. Text mining might aid database
curators to add experimental annotations from the scientific literature. Existing
extraction methods have difficulties to distinguish relationships between
proteins and cellular locations co-mentioned in the same sentence. RESULTS:
LocText was created as a new method to extract protein locations from abstracts
and full texts. LocText learned patterns from syntax parse trees and was trained
and evaluated on a newly improved LocTextCorpus. Combined with an automatic named
entity recognizer, LocText achieved high precision (P = 86%+/-4). After
completing development, we mined the latest research publications for three
organisms: human (Homo sapiens), budding yeast (Saccharomyces cerevisiae), and
thale cress (Arabidopsis thaliana). Examining 60 novel, text-mined annotations,
we found that 65% (human), 85% (yeast), and 80% (cress) were correct. Of all
validated annotations, 40% were completely novel, i.e. did neither appear in the
annotations nor the text descriptions of Swiss-Prot. CONCLUSIONS: LocText
provides a cost-effective, semi-automated workflow to assist database curators in
identifying novel protein localization annotations. The annotations suggested
through text-mining would be verified by experts to guarantee high-quality
standards of manually-curated databases such as Swiss-Prot.
PMID- 29343217
TI - Ceratocystis cacaofunesta genome analysis reveals a large expansion of
extracellular phosphatidylinositol-specific phospholipase-C genes (PI-PLC).
AB - BACKGROUND: The Ceratocystis genus harbors a large number of phytopathogenic
fungi that cause xylem parenchyma degradation and vascular destruction on a broad
range of economically important plants. Ceratocystis cacaofunesta is a
necrotrophic fungus responsible for lethal wilt disease in cacao. The aim of this
work is to analyze the genome of C. cacaofunesta through a comparative approach
with genomes of other Sordariomycetes in order to better understand the molecular
basis of pathogenicity in the Ceratocystis genus. RESULTS: We present an analysis
of the C. cacaofunesta genome focusing on secreted proteins that might constitute
pathogenicity factors. Comparative genome analyses among five Ceratocystidaceae
species and 23 other Sordariomycetes fungi showed a strong reduction in gene
content of the Ceratocystis genus. However, some gene families displayed a
remarkable expansion, in particular, the Phosphatidylinositol specific
phospholipases-C (PI-PLC) family. Also, evolutionary rate calculations suggest
that the evolution process of this family was guided by positive selection.
Interestingly, among the 82 PI-PLCs genes identified in the C. cacaofunesta
genome, 70 genes encoding extracellular PI-PLCs are grouped in eight small
scaffolds surrounded by transposon fragments and scars that could be involved in
the rapid evolution of the PI-PLC family. Experimental secretome using LC-MS/MS
validated 24% (86 proteins) of the total predicted secretome (342 proteins),
including four PI-PLCs and other important pathogenicity factors. CONCLUSION:
Analysis of the Ceratocystis cacaofunesta genome provides evidence that PI-PLCs
may play a role in pathogenicity. Subsequent functional studies will be aimed at
evaluating this hypothesis. The observed genetic arsenals, together with the
analysis of the PI-PLC family shown in this work, reveal significant differences
in the Ceratocystis genome compared to the classical vascular fungi, Verticillium
and Fusarium. Altogether, our analyses provide new insights into the evolution
and the molecular basis of plant pathogenicity.
PMID- 29343219
TI - The preliminary effect of whole-body vibration intervention on improving the
skeletal muscle mass index, physical fitness, and quality of life among older
people with sarcopenia.
AB - BACKGROUND: Studies have shown that sarcopenia easily leads to difficulty moving,
disability, and poor quality of life. However, researches on the use of whole
body vibration for older adults with sarcopenia living in institutions have been
lacking. Therefore, the main objective of the present study was to investigate
the effect of whole-body vibration intervention on improving the skeletal muscle
mass index, physical fitness, and quality of life of older adults with sarcopenia
living in institutions. METHODS: This study adopted a quasi-experimental, single
group, pretest-posttest design. The whole-body vibration intervention was
performed over a 3-month period, in which the older adults trained 3 times per
week; each training lasted 60 s with a break of 30 s for 10 repetitions. The
older adults' skeletal muscle mass index, physical fitness and quality of life
before and after the intervention of the whole-body vibration was collected.
Concerning the statistical methods adopted, nonparametric method-based tests were
employed. RESULTS: According to the results of analysis, after the intervention
of the 12-week whole-body vibration, the skeletal muscle mass index (z = - 3.621,
p = 0.000), physical fitness on standing on one foot (z = - 2.447, p = 0.014),
shoulder-arm flexibility (z = - 3.159, p = 0.002), 8-ft up and go test (z = -
2.692, p = 0.009), hand grip strength (z = - 3.388, p = 0.009), and five repeated
sit-to-stand tests (z = - 2.936, p = 0.003), all improved significantly.
Furthermore, concerning the quality of life of the older adults in the pretest
and posttest, the improvements were statistically significant (z = - 2.533, p =
0.011). CONCLUSIONS: The study results showed the effect of whole-body vibration
intervention on improving the skeletal muscle mass index, physical fitness, and
quality of life of sarcopenic older people living in institutions and could serve
as a crucial reference to health care professionals.
PMID- 29343221
TI - A case of molecularly profiled extraneural medulloblastoma metastases in a child.
AB - BACKGROUND: Extraneural metastases are relatively rare manifestations of
medulloblastoma. CASE PRESENTATION: We present the case of a young boy with group
three MYCN-amplified medulloblastoma. He received multimodal chemotherapy
consisting of gross total resection followed by postoperative craniospinal
radiation and adjuvant chemotherapy. The patient developed extraneural metastases
4 months after the end of therapy. Literature review identifies the poor
prognosis of MYCN-amplified medulloblastomas as well as extraneural metastases;
we review the current limitations and future directions of medulloblastoma
treatment options. CONCLUSION: To the best of our knowledge, this is the first
molecularly characterized report of extraneural metastases of medulloblastoma in
a child.
PMID- 29343220
TI - Antimicrobial resistance of Neisseria gonorrhoeae in Germany: low levels of
cephalosporin resistance, but high azithromycin resistance.
AB - BACKGROUND: The widespread antimicrobial resistance of Neisseria gonorrhoeae is a
serious problem for the treatment and control of gonorrhoea. Many of the
previously effective therapeutic agents are no longer viable. Because N.
gonorrhoeae infections are not reportable in Germany, only limited data on
disease epidemiology and antimicrobial susceptibility patterns are available. The
Gonococcal Resistance Network (GORENET) is a surveillance project to monitor
trends in the antimicrobial susceptibility of N. gonorrhoeae in Germany in order
to guide treatment algorithms and target future prevention strategies. METHODS:
Between April 2014 and December 2015, data on patient-related information were
collected from laboratories nationwide, and susceptibility testing was performed
on 537 N. gonorrhoeae isolates forwarded from the network laboratories to the
Conciliar Laboratory for gonococci. Susceptibility results for cefixime,
ceftriaxone, azithromycin, ciprofloxacin and penicillin were defined according to
EUCAST 4.0 standards. Percentages, medians and interquartile ranges (IQR) were
calculated. RESULTS: Altogether, 90% of isolates were from men. The median age
was 32 (IQR 25-44) years for men and 25 (IQR 22-40) years for women (p-value <
0.001). The most frequently tested materials among men were urethral (96.1%) and
rectal swabs (1.7%), and among women, it was mainly endocervical and vaginal
swabs (84.3%). None of the isolates were resistant to ceftriaxone. Furthermore,
1.9% (in 2014) and 1.4% (in 2015) of the isolates were resistant to cefixime,
11.9% and 9.8% showed resistance against azithromycin, 72.0% and 58.3% were
resistant to ciprofloxacin, and 29.1% and 18.8% were resistant to penicillin.
CONCLUSIONS: Resistance to ceftriaxone was not detected, and the percentage of
isolates with resistance to cefixime was low, whereas azithromycin resistance
showed high levels during the observation period. The rates of ciprofloxacin
resistance and penicillin resistance were very high across Germany. Continued
surveillance of antimicrobial drug susceptibilities for N. gonorrhoeae remains
highly important to ensure efficient disease management.
PMID- 29343222
TI - Transscleral tunnel incision related arterial hemorrhage in 23-gauge Vitrectomy:
case report.
AB - BACKGROUND: Transscleral tunnel incisions are commonly made to avoid
postoperative leakage in small gauge sutureless vitrectomy. We present an
unreported intraoperative complication, tunnel incision related arterial
hemorrhage from sclerotomy, in 23-gauge (23G) vitrectomy. CASE PRESENTATION: Two
cases of intraocular arterial hemorrhage from superonasal sclerotomy were
observed at the beginning of vitrectomy. The bleeding filled the vitreous cavity
quickly and gushed out from the incision port after the involved supronasal
cannula was removed. The active bleeding seemed not to stop spontaneously. We
controlled the active bleeding by relocating the involved cannula, elevating the
intraocular pressure and compressing the sclera wound. Post-operative intraocular
hemorrhage from the sclerotomy was not found in any of the two cases.
CONCLUSIONS: We suggest that the bleeding was from injured ciliary artery when
the incision crossed 3 or 9 o'clock accidently. Surgeons might avoid this
complication by locating the superior incisions away from the horizontal axis,
and should be aware the proper management.
PMID- 29343223
TI - The impact of age on the implementation of evidence-based medications in patients
with coronary artery disease and its prognostic significance: a retrospective
cohort study.
AB - BACKGROUND: Elderly patients with coronary artery disease (CAD) frequently
complicated with more cardiovascular risk factors, but received fewer evidence
based medications (EBMs). This study explored the association of EBMs compliance
in different age groups and the risk of long-term death. METHODS: A retrospective
analysis was conducted from a single registered database. 2830 consecutive
patients with CAD were enrolled and grouped into 3 categories by age. The primary
end point was all-cause mortality and secondary endpoint is cardiovascular
mortality. RESULTS: The mean follow-up time was 30.25 +/- 11.89 months and death
occurred in 270 cases,including 150 cases of cardiac death. Cumulative survival
curves indicated that the incidence rates of all-cause death and cardiovascular
death increased with age (older than 75 years old vs. 60 to 75 years old vs.
younger than 60 years old, mortality: 18.7% vs. 9.6% vs. 4.1%, p < 0.001;
cardiovascular mortality: 10.3% vs. 5.1% vs. 2.7%, p < 0.001). The percentage of
elderly patients using no EBMs was significantly higher than the percentages in
the other age group (7.7% vs. 4.6% vs. 2.2%,p < 0.05). Cox regression analysis
revealed the benefit of combination EBMs (all-cause mortality: hazard ratio [HR]
0.15, 95% CI 0.08-0.27; cardiac mortality: HR 0.08, 95% CI 0.04-0.19) for older
CAD patients. Similar trends were found about different kinds of EBMs in elderly
patients. CONCLUSIONS: Elderly patients with CAD had higher risk of death but a
lower degree of compliance with EBMs usage. Elderly CAD patients could receive
more clinical benefits by using EBMs.
PMID- 29343224
TI - Development and validation of self-reported line drawings of the modified
Beighton score for the assessment of generalised joint hypermobility.
AB - BACKGROUND: The impracticalities and comparative expense of carrying out a
clinical assessment is an obstacle in many large epidemiological studies. The
purpose of this study was to develop and validate a series of electronic self
reported line drawing instruments based on the modified Beighton scoring system
for the assessment of self-reported generalised joint hypermobility. METHODS:
Five sets of line drawings were created to depict the 9-point Beighton score
criteria. Each instrument consisted of an explanatory question whereby
participants were asked to select the line drawing which best represented their
joints. Fifty participants completed the self-report online instrument on two
occasions, before attending a clinical assessment. A blinded expert clinical
observer then assessed participants' on two occasions, using a standardised
goniometry measurement protocol. Validity of the instrument was assessed by
participant-observer agreement and reliability by participant repeatability and
observer repeatability using unweighted Cohen's kappa (k). Validity and
reliability were assessed for each item in the self-reported instrument
separately, and for the sum of the total scores. An aggregate score for
generalised joint hypermobility was determined based on a Beighton score of 4 or
more out of 9. RESULTS: Observer-repeatability between the two clinical
assessments demonstrated perfect agreement (k 1.00; 95% CI 1.00, 1.00). Self
reported participant-repeatability was lower but it was still excellent (k 0.91;
95% CI 0.74, 1.00). The participant-observer agreement was excellent (k 0.96; 95%
CI 0.87, 1.00). Validity was excellent for the self-report instrument, with a
good sensitivity of 0.87 (95% CI 0.81, 0.91) and excellent specificity of 0.99
(95% CI 0.98, 1.00). CONCLUSIONS: The self-reported instrument provides a valid
and reliable assessment of the presence of generalised joint hypermobility and
may have practical use in epidemiological studies.
PMID- 29343225
TI - Health worker knowledge of Integrated Disease Surveillance and Response standard
case definitions: a cross-sectional survey at rural health facilities in Kenya.
AB - BACKGROUND: The correct knowledge of standard case definition is necessary for
frontline health workers to diagnose suspected diseases across Africa. However,
surveillance evaluations commonly assume this prerequisite. This study assessed
the knowledge of case definitions for health workers and their supervisors for
disease surveillance activities in rural Kenya. METHODS: A cross-sectional survey
including 131 health workers and their 11 supervisors was undertaken in two
counties in Kenya. Descriptive analysis was conducted to classify the correctness
of knowledge into four categories for three tracer diseases (dysentery, measles,
and dengue). We conducted a univariate and multivariable logistic regression
analyses to explore factors influencing knowledge of the case definition for
dysentery. RESULTS: Among supervisors, 81.8% knew the correct definition for
dysentery, 27.3% for measles, and no correct responses were provided for dengue.
Correct knowledge was observed for 50.4% of the health workers for dysentery,
only 12.2% for measles, and none for dengue. Of 10 examined factors, the
following were significantly associated with health workers' correct knowledge of
the case definition for dysentery: health workers' cadre (aOR 2.71; 95% CI 1.20
6.12; p = 0.017), and display of case definition poster (aOR 2.24; 95% CI 1.01
4.98; p = 0.048). Health workers' exposure to the surveillance refresher
training, supportive supervision and guidelines were not significantly associated
with the knowledge. CONCLUSION: The correct knowledge of standard case
definitions was sub-optimal among health workers and their supervisors, which is
likely to impact the reliability of routine surveillance reports generated from
health facilities.
PMID- 29343226
TI - Binge eating disorder and depressive symptoms among females of child-bearing age:
the Korea Nurses' Health Study.
AB - BACKGROUND: Most studies regarding the relationship between binge eating disorder
(BED) and depression have targeted obese populations. However, nurses,
particularly female nurses, are one of the vocations that face these issues due
to various reasons including high stress and shift work. This study investigated
the prevalence of BED and the correlation between BED and severity of self
reported depressive symptoms among female nurses in South Korea. METHODS:
Participants were 7,267 female nurses, of which 502 had symptoms of BED. Using
the propensity score matching (PSM) technique, 502 nurses with BED and 502
without BED were included in the analyses. Data were analyzed using descriptive
statistics, Spearman's correlation, and multivariable ordinal logistic regression
analysis. RESULTS: The proportion of binge eating disorder was 6.90% among the
nurses, and 81.3% of nurses displayed some levels of depressive symptoms.
Multivariable ordinal logistic regression analysis revealed that age (40 years
old and older), alcohol consumption (frequent drinkers), self-rated health, sleep
problems, and stress were associated with self-reported depression symptoms.
Overall, after adjusting for confounders, nurses with BED had 1.80 times the risk
(95% CI = [1.41-2.30]; p-value < 0.001) of experiencing a greater severity of
self-reported depression symptoms. CONCLUSIONS: Korean female nurse showed a
higher prevalence of both binge eating disorder and depressive symptoms, and the
association between the two factors was proven in the study. Therefore, hospital
management and health policy makers should be alarmed and agreed on both
examining nurses on such problems and providing organized and systematic
assistance.
PMID- 29343227
TI - Associations among maternal pre-pregnancy body mass index, gestational weight
gain and risk of autism in the Han Chinese population.
AB - BACKGROUND: Autism is a neurodevelopmental disorder with an unclear etiology. Pre
pregnancy body mass index (BMI) and gestational weight gain (GWG) have been
suggested to play a role in the etiology of autism. The current study explores
the associations among maternal pre-pregnancy BMI, GWG and the risk of autism in
the Han Chinese population. METHODS: Demographic information, a basic medical
history and information regarding maternal pre-pregnancy and pregnancy conditions
were collected from the parents of 705 Han Chinese children with autism and 2236
unrelated typically developing children. Binary logistic regressions were
conducted to calculate the odds ratio (OR) for the relationship among pre
pregnancy BMI, GWG and the occurrence of autism. The interaction between pre
pregnancy BMI and GWG was analyzed by performing stratification analyses using a
logistic model. RESULTS: After adjusting for the children's gender, parental age
and family annual income, excessive GWG was associated with autism risk in the
entire sample (OR = 1.327, 95% CI: 1.021-1.725), whereas the relationship between
maternal pre-pregnancy BMI and autism was not significant. According to the
stratification analyses, excessive GWG increased the risk of autism in
overweight/obese mothers (OR = 2.468, 95% CI: 1.102-5.526) but not in underweight
or normal weight mothers. CONCLUSIONS: The maternal pre-pregnancy BMI might not
be independently associated with autism risk. However, excessive GWG might
increase the autism risk of offspring of overweight and obese mothers.
PMID- 29343228
TI - Problematic internet use and psychiatric co-morbidity in a population of Japanese
adult psychiatric patients.
AB - BACKGROUND: Many studies reported the high prevalence of problematic internet use
(PIU) among adolescents (13-50%), and PIU was associated with various psychiatric
symptoms. In contrast, only a few studies investigated the prevalence among the
adult population (6%). This study aimed to investigate the prevalence of PIU and
psychiatric co-morbidity among adult psychiatric patients. METHODS: Three hundred
thirty-three adult psychiatric patients were recruited over a 3-month period. Two
hundred thirty-one of them completed the survey (response rate: 69.4%, 231/333;
Male/Female/Transgender: 90/139/2; mean age = 42.2). We divided participants into
"normal internet users" and "problematic internet users" using a combination of
Young's Internet Addiction Test (IAT) and the Compulsive Internet Use Scale
(CIUS). Demographic data and comorbid psychiatric symptoms were compared between
the two groups using self-rating scales measuring insomnia (Athens Insomnia
Scale, AIS), depression (Beck Depression Inventory, BDI), anxiety (State-trait
Anxiety Inventory, STAI), attention deficit hyperactivity disorder (ADHD) (Adult
ADHD Self-report Scale, ASRS), autism (Autism Spectrum Quotient, AQ), obsessive
compulsive disorder (OCD) (Obsessive-Compulsive Inventory, OCI), social anxiety
disorder (SAD) (Liebowitz Social Anxiety Scale, LSAS), alcohol abuse, and
impulsivity (Barratt Impulsive Scale, BIS). RESULTS: Among 231 respondents, 58
(25.1%) were defined as problematic internet users, as they scored high on the
IAT (40 or more) or CIUS (21 or more). The age of problematic internet users was
significantly lower than that of normal internet users (p < 0.001, Mann-Whitney U
test). The problematic internet users scored significantly higher on scales
measuring sleep problems (AIS, 8.8 for problematic internet users vs 6.3 for
normal internet users, p < 0.001), depression (BDI, 27.4 vs 18.3, p < 0.001),
trait anxiety (STAI, 61.8 vs 53.9, p < 0.001), ADHD (ASRS, part A 3.1 vs 1.8 and
part B 3.5 vs 1.8, p < 0.001), autism (AQ, 25.9 vs 21.6, p < 0.001), OCD (OCI,
63.2 vs 36.3, p < 0.001), SAD (LSAS, 71.4 vs 54.0, p < 0.001), and impulsivity
(BIS, 67.4 vs 63.5, p = 0.004). CONCLUSIONS: The prevalence of PIU among adult
psychiatric patients is relatively high. As previous studies reported in the
general population, lower age and psychiatric comorbidity were associated with
PIU among adult psychiatric patients. More research is needed to determine any
causal relations between PIU and psychopathological illnesses.
PMID- 29343229
TI - The Colombo Twin and Singleton Follow-up Study: a population based twin study of
psychiatric disorders and metabolic syndrome in Sri Lanka.
AB - BACKGROUND: The disease burden related to mental disorders and metabolic syndrome
is growing in low-and middle-income countries (LMIC). The Colombo Twin and
Singleton Study (COTASS) is a population-based sample of twins and singletons in
Colombo, Sri Lanka. Here we present prevalence estimates for metabolic syndrome
(metS) and mental disorders from a follow-up (COTASS-2) of the original study
(COTASS-1), which was a mental health survey. METHODS: In COTASS-2, participants
completed structured interviews, anthropometric measures and provided fasting
blood and urine samples. Depressive disorder, depressive symptoms, anxiety
symptoms, post-traumatic stress disorder (PTSD) and hazardous alcohol use were
ascertained with structured psychiatric screens (Composite International
Diagnostic Interview (CIDI), Beck Depression Inventory (BDI-II), Generalised
Anxiety Disorder Questionnaire (GAD-7), PTSD Checklist - Civilian Version (PCL
C), and Alcohol Use Disorders Identification Test (AUDIT)). We defined metS
according to the International Diabetes Federation (IDF) criteria and the revised
National Cholesterol Education Programme Adult Treatment Panel (NCEP ATP III)
criteria. We estimated the prevalence of psychiatric disorders and metS and metS
components, and associations with gender, education and age. RESULTS: Two
thousand nine hundred thirty-four twins and 1035 singletons were followed up from
COTASS-1 (83.4 and 61.8% participation rate, respectively). Prevalence estimates
for depressive disorder (CIDI), depressive symptoms (BDI >= 16), anxiety symptoms
(GAD-7 >= 10) and PTSD (PCL-C DSM criteria) were 3.8, 5.9, 3.6, and 4.5%
respectively for twins and 3.9, 9.8, 5.1 and 5.4% for singletons. 28.1 and 30.9%
of male twins and singletons respectively reported hazardous alcohol use.
Approximately one third met the metS criteria (IDF: 27.4% twins, 44.6%
singletons; NCEP ATP III: 30.6% twins, 48.6% singletons). The most prevalent
components were central obesity (59.2% twins, 71.2% singletons) and raised
fasting blood glucose or diabetes (38.2% twins, 56.7% singletons). CONCLUSION:
MetS was highly prevalent in twins, and especially high in singletons, whereas
the prevalence of mental disorders was low, but consistent with local estimates.
The high levels of raised fasting plasma glucose and central obesity were
particularly concerning, and warrant national diabetes prevention programmes.
PMID- 29343230
TI - The SyBil-AA real-time fMRI neurofeedback study: protocol of a single-blind
randomized controlled trial in alcohol use disorder.
AB - BACKGROUND: Alcohol Use Disorder is a highly prevalent mental disorder which puts
a severe burden on individuals, families, and society. The treatment of Alcohol
Use Disorder is challenging and novel and innovative treatment approaches are
needed to expand treatment options. A promising neuroscience-based intervention
method that allows targeting cortical as well as subcortical brain processes is
real-time functional magnetic resonance imaging neurofeedback. However, the
efficacy of this technique as an add-on treatment of Alcohol Use Disorder in a
clinical setting is hitherto unclear and will be assessed in the Systems Biology
of Alcohol Addiction (SyBil-AA) neurofeedback study. METHODS: N = 100 patients
with Alcohol Use Disorder will be randomized to 5 parallel groups in a single
blind fashion and receive real-time functional magnetic resonance imaging
neurofeedback while they are presented pictures of alcoholic beverages. The
groups will either downregulate the ventral striatum, upregulate the right
inferior frontal gyrus, negatively modulate the connectivity between these
regions, upregulate, or downregulate the auditory cortex as a control region.
After receiving 3 sessions of neurofeedback training within a maximum of 2 weeks,
participants will be followed up monthly for a period of 3 months and relapse
rates will be assessed as the primary outcome measure. DISCUSSION: The results of
this study will provide insights into the efficacy of real-time functional
magnetic resonance imaging neurofeedback training in the treatment of Alcohol Use
Disorder as well as in the involved brain systems. This might help to identify
predictors of successful neurofeedback treatment which could potentially be
useful in developing personalized treatment approaches. TRIAL REGISTRATION: The
study was retrospectively registered in the German Clinical Trials Register
(trial identifier: DRKS00010253 ; WHO Universal Trial Number (UTN): U1111-1181
4218) on May 10th, 2016.
PMID- 29343231
TI - Cementless unicompartmental knee replacement allows early return to normal
activity.
AB - BACKGROUND: Physical activity and regular participation in recreational sports
gain importance in patients' lifestyle after knee arthroplasty. Cementless
unicompartimental Knee replacement with the Oxford System has been introduced
into clinical routine. Currently there is no data reporting on the physical
activity, return to sports rate and quality of live after medial cementless
Oxford Unicompartimental Knee Replacement (OUKR). METHODS: This retrospective
cohort study reports on the functional outcome of the first 27 consecutive
patients (30 knees) that were consecutively treated with a cementless medial OUKR
between 2007 and 2009 in our hospital. Physical activity and quality of life were
measured using the Tegner-Score, the UCLA-Activity Score, the Schulthess Clinical
Activity Questionnaire and the SF-36 Score. The patients' satisfaction with the
outcome was measured using a visual analogue scale. RESULTS: Mean age at surgery
was 62.5 years. Patients showed a rapid recovery with 17 out of 27 patients
returning to sports within 3 months, 24 within 6 months after surgery. The Return
to-activity-rate was 100%. 10 out of 27 patients showed a high activity level
(UCLA >=7 points) with a mean postoperative UCLA-Score of 6.1 points.
CONCLUSIONS: Patients recover rapidly after cementless OUKR with a return to
sports rate of 100% and patients are able to participate in high impact sports
disciplines.
PMID- 29343232
TI - Intravenous dexmedetomidine pre-medication reduces the required minimum alveolar
concentration of sevoflurane for smooth tracheal extubation in anesthetized
children: a randomized clinical trial.
AB - BACKGROUND: It has been known that Dexmedetomidine pre-medication enhances the
effects of volatile anesthetics, reduces the need of sevoflurane, and facilitates
smooth extubation in anesthetized children. This present study was designed to
determine the effects of different doses of intravenous dexmedetomidine pre
medication on minimum alveolar concentration of sevoflurane for smooth tracheal
extubation (MACEX) in anesthetized children. METHODS: A total of seventy-five
pediatric patients, aged 3-7 years, ASA physical status I and II, and undergoing
tonsillectomy were randomized to receive intravenous saline (Group D0),
dexmedetomidine 1 MUg?kg-1 (Group D1), or dexmedetomidine 2 MUg?kg-1 (Group D2)
approximately 10 min before anesthesia start. Sevoflurane was used for anesthesia
induction and anesthesia maintenance. At the end of surgery, the initial
concentration of sevoflurane for smooth tracheal extubation was determined
according to the modified Dixon's "up-and-down" method. The starting sevoflurane
for the first patient was 1.5% in Group D0, 1.0% in Group D1, and 0.8% in Group
D2, with subsequent 0.1% up or down in next patient based on whether smooth
extubation had been achieved or not in current patient. The endotreacheal tube
was removed after the predetermined concentration had been maintained constant
for ten minutes. All responses ("smooth" or "not smooth") to tracheal extubation
and respiratory complications were assessed. RESULTS: MACEX values of sevoflurane
in Group D2 (0.51 +/- 0.13%) was significantly lower than in Group D1 (0.83 +/-
0.10%; P < 0.001), the latter being significantly lower than in Group D0 (1.40 +/
0.12%; P < 0.001). EC95 values of sevoflurane were 0.83%, 1.07%, and 1.73% in
Group D2, Group D1, and Group D0, respectively. No patient in the current study
had laryngospasm. CONCLUSION: Dexmedetomidine decreased the required MACEX values
of sevoflurane to achieve smooth extubation in a dose-dependent manner.
Intravenous dexmedetomidine 1 MUg?kg-1 and 2 MUg?kg-1 pre-medication decreased
MACEX by 41% and 64%, respectively. TRIAL REGISTRATION: Chinese Clinical Trial
Registry (ChiCTR): ChiCTR-IOD-17011601 , date of registration: 09 Jun 2017,
retrospectively registered.
PMID- 29343233
TI - Alcohol use and sickness absence due to all causes and mental- or musculoskeletal
disorders: a nationally representative study.
AB - BACKGROUND: Previous studies have not distinguished between different alcohol-use
histories, which could have contributed to the current inconsistent evidence
regarding the relationship between alcohol use and subsequent sickness absence.
We thus examined alcohol use and subsequent diagnosis-specific sickness absence
in groups with different levels of alcohol use, as well as in lifelong
abstainers, former drinkers, and people with clinical alcohol use disorders.
METHODS: The data of the population-based Health 2000 Survey (BRIF8901) of 3666
Finns aged 30-55 were linked with national registers on medically certified
sickness absences lasting for > 10 working days (long-term) for all causes (2000
2010) and for mental or musculoskeletal disorders (2004-2010), as well as with
registers on pensions and death (2000-2010). Alcohol use was assessed by
questionnaire. Chronic somatic diseases were evaluated at baseline in a clinical
examination, and common mental and alcohol use disorders using the Composite
International Diagnostic Interview (CIDI). Cox regression analyses were conducted
with censoring for death and retirement from work. RESULTS: During an average 10
year follow-up, 56.0% of the participants had at least one long-term sickness
absence period. Compared with light drinkers, those having an alcohol use
disorder had increased risk of all-cause sickness absence (HR = 1.27; 95% CI =
1.04 - 1.54) and sickness absence due to mental disorders (HR = 2.16; 95% CI =
1.39 - 3.35), when somatic and mental disorders as well as demographic, lifestyle
related and occupational factors at baseline were accounted for. Lifelong
abstainers did not differ from light drinkers. Also high-volume drinking (HR =
1.52; 95% CI 1.03 - 2.25) and former drinking (HR = 1.57; 95% CI = 1.15 - 2.15)
were associated with long-term sickness absence due to mental disorders. Alcohol
use was not predictive of sickness absence due to musculoskeletal disorders.
CONCLUSIONS: These results highlight the need to distinguish between former
drinking and lifelong abstinence, as only former drinking was associated with
sickness absence. Alcohol use disorder and high-volume drinking were strongly
predictive of sickness absence due to mental disorders. Identifying people with
excessive alcohol use e.g. in occupational health care, and mapping and
supporting their mental health may help in preventing sickness absences.
PMID- 29343234
TI - From the day they are born: a qualitative study exploring violence against
children with disabilities in West Africa.
AB - BACKGROUND: Despite the building evidence on violence against children globally,
almost nothing is known about the violence children with disabilities in low and
middle-income countries (LMICs) experience. The prevalence of violence against
children with disabilities can be expected to be higher in LMICs where there are
greater stigmas associated with having a child with a disability, less resources
for families who have children with disabilities, and wider acceptance of the use
of corporal punishment to discipline children. This study explores violence
experienced by children with disabilities based on data collected from four
countries in West Africa- Guinea, Niger, Sierra Leone, and Togo. METHODS: A
qualitative study design guided data generation with a total of 419 children,
community members, and disability stakeholders. Participants were selected using
purposive sampling. Stakeholders shared their observations of or experiences of
violence against children with disabilities in their community in interviews and
focus groups. Thematic analysis guided data analysis and identified patterns of
meaning among participants' experiences. RESULTS: Results illuminate that
children with disabilities experience violence more than non-disabled children,
episodes of violence start at birth, and that how children with disabilities
participate in their communities contributes to their different experiences of
violence. CONCLUSIONS: The study recommends policy-oriented actions and
prevention programs that include children and their families in strategizing ways
to address violence.
PMID- 29343236
TI - Barriers to timely diagnosis of interstitial lung disease in the real world: the
INTENSITY survey.
AB - BACKGROUND: The diagnosis of idiopathic pulmonary fibrosis (IPF) and other
interstitial lung diseases (ILD) presents significant clinical challenges. To
gain insights regarding the diagnostic experience of patients with ILD and to
identify potential barriers to a timely and accurate diagnosis, we developed an
online questionnaire and conducted a national survey of adults with a self
reported diagnosis of ILD. METHODS: A pre-specified total of 600 subjects were
recruited to participate in a 40-question online survey. E-mail invitations
containing a link to the survey were sent to 16 427 registered members of the
Pulmonary Fibrosis Foundation. Additionally, an open invitation was posted on an
online forum for patients and caregivers ( www.inspire.com ). The recruitment and
screening period was closed once the pre-defined target number of respondents was
reached. Eligible participants were adult U.S. residents with a diagnosis of IPF
or a non-IPF ILD. RESULTS: A total of 600 eligible respondents met the
eligibility criteria and completed the survey. Of these, 55% reported >= 1
misdiagnosis and 38% reported >= 2 misdiagnoses prior to the current diagnosis.
The most common misdiagnoses were asthma (13.5%), pneumonia (13.0%), and
bronchitis (12.3%). The median time from symptom onset to current diagnosis was 7
months (range, 0-252 months), with 43% of respondents reporting a delay of >= 1
year and 19% reporting a delay of >= 3 years. Sixty-one percent of respondents
underwent at least one invasive diagnostic procedure. CONCLUSIONS: While a
minority of patients with ILD will experience an appropriate and expedient
diagnosis, the more typical diagnostic experience for individuals with ILD is
characterized by considerable delays, frequent misdiagnosis, exposure to costly
and invasive diagnostic procedures, and substantial use of healthcare resources.
These findings suggest a need for physician education, development of clinical
practice recommendations, and improved diagnostic tools aimed at improving
diagnostic accuracy in patients with ILD.
PMID- 29343235
TI - Comparison of three assembly strategies for a heterozygous seedless grapevine
genome assembly.
AB - BACKGROUND: De novo heterozygous assembly is an ongoing challenge requiring
improved assembly approaches. In this study, three strategies were used to
develop de novo Vitis vinifera 'Sultanina' genome assemblies for comparison with
the inbred V. vinifera (PN40024 12X.v2) reference genome and a published
Sultanina ALLPATHS-LG assembly (AP). The strategies were: 1) a default PLATANUS
assembly (PLAT_d) for direct comparison with AP assembly, 2) an iterative merging
strategy using METASSEMBLER to combine PLAT_d and AP assemblies (MERGE) and 3)
PLATANUS parameter modifications plus GapCloser (PLAT*_GC). RESULTS: The three
new assemblies were greater in size than the AP assembly. PLAT*_GC had the
greatest number of scaffolds aligning with a minimum of 95% identity and >=1000
bp alignment length to V. vinifera (PN40024 12X.v2) reference genome. SNP
analysis also identified additional high quality SNPs. A greater number of
sequence reads mapped back with zero-mismatch to the PLAT_d, MERGE, and PLAT*_GC
(>94%) than was found in the AP assembly (87%) indicating a greater fidelity to
the original sequence data in the new assemblies than in AP assembly. A de novo
gene prediction conducted using seedless RNA-seq data predicted > 30,000 coding
sequences for the three new de novo assemblies, with the greatest number (30,544)
in PLAT*_GC and only 26,515 for the AP assembly. Transcription factor analysis
indicated good family coverage, but some genes found in the VCOST.v3 annotation
were not identified in any of the de novo assemblies, particularly some from the
MYB and ERF families. CONCLUSIONS: The PLAT_d and PLAT*_GC had a greater number
of synteny blocks with the V. vinifera (PN40024 12X.v2) reference genome than AP
or MERGE. PLAT*_GC provided the most contiguous assembly with only 1.2% scaffold
N, in contrast to AP (10.7% N), PLAT_d (6.6% N) and Merge (6.4% N). A PLAT*_GC
pseudo-chromosome assembly with chromosome alignment to the reference genome V.
vinifera, (PN40024 12X.v2) provides new information for use in seedless grape
genetic mapping studies. An annotated de novo gene prediction for the PLAT*_GC
assembly, aligned with VitisNet pathways provides new seedless grapevine specific
transcriptomic resource that has excellent fidelity with the seedless short read
sequence data.
PMID- 29343238
TI - The slowing pace of life expectancy gains since 1950.
AB - BACKGROUND: New technological breakthroughs in biomedicine should have made it
easier for countries to improve life expectancy at birth (LEB). This paper
measures the pace of improvement in the decadal gains of LEB, for the last 60
years adjusting for each country's starting point of LEB. METHODS: LEB increases
over the next 10-years for 139 countries between 1950 and 2009 were regressed on
LEB, GDP, total fertility rate, population density, CO2 emissions, and HIV
prevalence using country-specific fixed effects and time-dummies. Analysis
grouped countries into one-of-four strata: LEB < 51, 51 <= LEB < 61, 61 <= LEB <
71, and LEB >= 71. RESULTS: The rate of increase of LEB has fallen consistently
since 1950 across all strata. Results hold in unadjusted analysis and in the
regression-adjusted analysis. LEB decadal gains fell from 4.80 (IQR: 2.98-6.20)
years in the 1950s to 2.39 (IQR:1.80-2.80) years in the 2000s for the healthiest
countries (LEB >= 71). For countries with the lowest LEB (LEB < 51), decadal
gains fell from 7.38 (IQR:4.83-9.25) years in the 1950s to negative 6.82 (IQR:
12.95--1.05) years in the 2000s. Multivariate analysis controlling for HIV
prevalence, GDP, and other covariates shows a negative effect of time on LEB
decadal gains among all strata. CONCLUSIONS: Contrary to the expectation that
advances in health technology and spending would hasten improvements in LEB, we
found that the pace-of-growth of LEB has slowed around the world.
PMID- 29343237
TI - Subtypes in clinical burnout patients enrolled in an employee rehabilitation
program: differences in burnout profiles, depression, and recovery/resources
stress balance.
AB - BACKGROUND: Burnout is generally perceived a unified disorder with homogeneous
symptomatology across people (exhaustion, cynicism, and reduced professional
efficacy). However, increasing evidence points to intra-individual patterns of
burnout symptoms in non-clinical samples such as students, athletes, healthy, and
burned-out employees. Different burnout subtypes might therefore exist. Yet,
burnout subtypes based on burnout profiles have hardly been explored in clinical
patients, and the samples investigated in previous studies were rather
heterogeneous including patients with various physical, psychological, and social
limitations, symptoms, and disabilities. Therefore, the aim of this study is to
explore burnout subtypes based on burnout profiles in clinically diagnosed
burnout patients enrolled in an employee rehabilitation program, and to
investigate whether the subtypes differ in depression, recovery/resources-stress
balance, and sociodemographic characteristics. METHODS: One hundred three
patients (66 women, 37 men) with a clinical burnout diagnosis, who were enrolled
in a 5 week employee rehabilitation program in two specialized psychosomatic
clinics in Austria, completed a series of questionnaires including the Maslach
Burnout Inventory - General Survey (MBI-GS), the Beck Depression Inventory, and
the Recovery-Stress-Questionnaire for Work. Cluster analyses with the three MBI
GS subscales as clustering variables were used to identify the burnout subtypes.
Subsequent multivariate/univariate analysis of variance and Pearson chi-square
tests were performed to investigate differences in depression, recovery/resources
stress balance, and sociodemographic characteristics. RESULTS: Three different
burnout subtypes were discovered: the exhausted subtype, the exhausted/cynical
subtype, and the burned-out subtype. The burned-out subtype and the
exhausted/cynical subtype showed both more severe depression symptoms and a worse
recovery/resources-stress balance than the exhausted subtype. Furthermore, the
burned-out subtype was more depressed than the exhausted/cynical subtype, but no
difference was observed between these two subtypes with regard to perceived
stress, recovery, and resources. Sociodemographic characteristics were not
associated with the subtypes. CONCLUSIONS: The present study indicates that there
are different subtypes in clinical burnout patients (exhausted,
exhausted/cynical, and burned-out), which might represent patients at different
developmental stages in the burnout cycle. Future studies need to replicate the
current findings, investigate the stability of the symptom patterns, and examine
the efficacy of rehabilitation interventions in different subtypes.
PMID- 29343239
TI - Calcium-dependent protein kinases in cotton: insights into early plant responses
to salt stress.
AB - BACKGROUND: Soil salinization is one of the major environmental constraints to
plant growth and agricultural production worldwide. Signaling components
involving calcium (Ca2+) and the downstream calcium-dependent protein kinases
(CPKs) play key roles in the perception and transduction of stress signals.
However, the study of CPKs in cotton and their functions in response to salt
stress remain unexplored. RESULTS: A total of 98 predicted CPKs were identified
from upland cotton (Gossypium hirsutum L. 'TM-1'), and phylogenetic analyses
classified them into four groups. Gene family distribution studies have revealed
the substantial impacts of the genome duplication events to the total number of
GhCPKs. Transcriptome analyses showed a wide distribution of CPKs' expression
among different organs. A total of 19 CPKs were selected for their rapid
responses to salt stress at the transcriptional level, most of which were also
incduced by the thylene-releasing chemical ethephon, suggesting a partal overlap
of the salinity and ethylene responses. Silencing of 4 of the 19 CPKs (GhCPK8,
GhCPK38, GhCPK54, and GhCPK55) severely compromised the basal cotton resistance
to salt stress. CONCLUSIONS: Our genome-wide expression analysis of CPK genes
from up-land cotton suggests that CPKs are involved in multiple developmental
responses as well as the response to different abiotic stresses. A cluster of the
cotton CPKs was shown to participate in the early signaling events in cotton
responses to salt stress. Our results provide significant insights on functional
analysis of CPKs in cotton, especially in the context of cotton adaptions to salt
stress.
PMID- 29343240
TI - Attempted suicide of ethnic minority girls with a Caribbean and Cape Verdean
background: rates and risk factors.
AB - BACKGROUND: WHO data shows that female immigrants in Europe attempt suicide at
higher rates than 'native' women and 'native' and immigrant men. Empirical
studies addressing attempted suicide of female immigrants of Caribbean (Antillean
Dutch and Creole-Surinamese-Dutch) as well as Cape Verdean descent in Europe are
however scarce. We aim to increase knowledge about rates and risk factors of
girls of Caribbean and Cape Verdean descent living in the Netherlands. METHODS:
We conducted logistic regression on a dataset that consisted of self-reported
health and well-being surveys filled out by 5611 female students, age 14-16, in
Rotterdam, the Netherlands (Antillean Dutch N = 357, Creole-Surinamese-Dutch N =
130, and Cape Verdean-Dutch N = 402, and Dutch 'natives' N = 4691). We studied if
girls of these minority groups had elevated risk for attempted suicide. Risk
indicators that were suspected to play a role were investigated i.e. household
composition, socio-economic class, externalizing problems, emotional problems and
sexual abuse. RESULTS: We found that rates of attempted suicide among Antillean
(14%), Creole-Surinamese young women (15.4%) were higher than of 'native' Dutch
girls (9.1%), while rates of Cape-Verdean girls (8.3%) were rather similar to
those of 'native' girls. Not living with two biological parents was a risk factor
for 'native' girls, but not for girls of Caribbean and Cape Verdean descent.
Emotional problems and sexual abuse seems to be a risk indicator for suicidality
across all ethnicities. Aggressive behaviour was a risk factor for Antillean
Dutch and 'native' girls. CONCLUSIONS: Our findings underscore the need for
developing suicide prevention programs for minority girls in multicultural cities
in western Europe, in particular those of Caribbean descent. Results suggest the
importance of addressing socio-economic class and educational background for
suicide prevention, which bear particular relevance for Caribbean populations.
Referral in the case of sexual trauma and low psychological wellbeing seems
critical for reducing suicidal behaviour in girls, regardless of ethnicity.
PMID- 29343241
TI - Clinical features and dysfunctions of iron metabolism in Parkinson disease
patients with hyper echogenicity in substantia nigra: a cross-sectional study.
AB - BACKGROUND: Transcranial ultrasound is a useful tool for providing the evidences
for the early diagnosis and differential diagnosis of Parkinson disease (PD).
However, the relationship between hyper echogenicity in substantia nigra (SN) and
clinical symptoms of PD patients remains unknown, and the role of dysfunction of
iron metabolism on the pathogenesis of SN hyper echogenicity is unclear. METHODS:
PD patients was detected by transcranial sonography and divided into with no
hyper echogenicity (PDSN-) group and with hyper echogenicity (PDSN+) group. Motor
symptoms (MS) and non-motor symptoms (NMS) were evaluated, and the levels of iron
and related proteins in serum and cerebrospinal fluid (CSF) were detected for PD
patients. Data comparison between the two groups and correlation analyses were
performed. RESULTS: PDSN+ group was significantly older, and had significantly
older age of onset, more advanced Hohen-Yahr stage, higher SCOPA-AUT score and
lower MoCA score than PDSN- group (P < 0.05). Compared with PDSN- group, the
levels of transferrin and light-ferritin in serum and iron level in CSF were
significantly elevated (P < 0.05), but ferroportin level in CSF was significantly
decreased in PDSN+ group (P < 0.05). CONCLUSIONS: PD patients with hyper
echogenicity in SN are older, at more advanced disease stage, have severer motor
symptoms, and non-motor symptoms of cognitive impairment and autonomic
dysfunction. Hyper echogenicity of SN in PD patients is related to dysfunction of
iron metabolism, involving increased iron transport from peripheral system to
central nervous system, reduction of intracellular iron release and excessive
iron deposition in brain.
PMID- 29343242
TI - Stage of cancer diagnoses among migrants from the former Soviet Union in
comparison to the German population - are diagnoses among migrants delayed?
AB - BACKGROUND: In this study, we compared stage at diagnosis, standardized incidence
ratio (SIR) and standardized mortality ratio (SMR) of most frequent cancer
diagnoses between re-settlers (Aussiedler) from the former Soviet Union and the
general population in the Saarland in Germany to assess possible delays in
diagnosis of cancer among this migrant group. METHODS: Lung cancer, colorectal
cancer, breast cancer, prostate cancer, malignant melanoma of the skin and
stomach cancer diagnoses among a cohort of 18,619 re-settlers living in the
Saarland between 1990 and 2009 were identified by the federal state's cancer
registry. Vital status was available for the respective time-period and used to
calculate SIR and SMR in comparison to the autochthonous population. Tumor stages
were condensed into local and advanced stages. Odds ratios (OR) for an advanced
tumor stage were modeled in dependence of re-settler-status and relevant
covariates by logistic regression. Missing values were addressed in a sensitivity
analysis. The influence of duration of stay in Germany on advanced stage
diagnosis was analyzed among re-settlers. RESULTS: SIR and SMR of lung and breast
cancer were lower among female re-settlers, while SIR and SMR of colorectal and
prostate cancer were lower among male re-settlers. SIR and SMR of stomach cancer
were elevated among both sexes. Female re-settlers showed an elevated OR for
being diagnosed with advanced stage breast cancer. Both male and female re
settlers showed an elevated OR when observing all six sites combined (OR among
males 1.47, p = 0.04; OR among females 1.37, p = 0.05). The result of elevated
ORs was supported in the sensitivity analysis. Finally, male re-settlers showed a
weak association between duration of stay in Germany and reduced risk for
advanced stage diagnosis. CONCLUSION: Re-settlers were more likely to be
diagnosed at an advanced tumor stage. These findings are in line with previous
research having shown unfavorable health care utilization of re-settlers.
Overall, low mortality rates despite an increased risk of advanced stage at
diagnosis argue for a sufficient follow-up care, comparable to the autochthonous
population.
PMID- 29343243
TI - Retrospectively assessed psychosocial working conditions as predictors of
prospectively assessed sickness absence and disability pension among older
workers.
AB - BACKGROUND: The aim was to explore the association between retrospectively
assessed psychosocial working conditions during working life and prospectively
assessed risk of sickness absence and disability pension among older workers.
METHODS: The prospective risk of register-based long-term sickness absence (LTSA)
and disability pension was estimated from exposure to 12 different psychosocial
work characteristics during working life among 5076 older workers from the CAMB
cohort (Copenhagen Aging and Midlife Biobank). Analyses were censored for
competing events and adjusted for age, gender, physical work environment,
lifestyle, education, and prior LTSA. RESULTS: LTSA was predicted by high levels
of cognitive demands (HR 1.31 (95% CI 1.10-1.56)), high levels of emotional
demands (HR 1.26 (95% CI 1.07-1.48)), low levels of influence at work (HR 1.30
(95% CI 1.03-1.64)), and high levels of role conflicts (HR 1.34 (95% CI 1.09
1.65)). Disability pension was predicted by low levels of influence at work (HR
2.73 (95% CI 1.49-5.00)) and low levels of recognition from management (HR 2.04
(95% CI 1.14-3.67)). CONCLUSIONS: This exploratory study found that
retrospectively assessed high cognitive demands, high and medium emotional
demands, low influence at work, low recognition from management, medium role
clarity, and high role conflicts predicted LTSA and/or disability pension.
PMID- 29343244
TI - Hsp70 at the membrane: driving protein translocation.
AB - Efficient movement of proteins across membranes is required for cell health. The
translocation process is particularly challenging when the channel in the
membrane through which proteins must pass is narrow-such as those in the
membranes of the endoplasmic reticulum and mitochondria. Hsp70 molecular
chaperones play roles on both sides of these membranes, ensuring efficient
translocation of proteins synthesized on cytosolic ribosomes into the interior of
these organelles. The "import motor" in the mitochondrial matrix, which is
essential for driving the movement of proteins across the mitochondrial inner
membrane, is arguably the most complex Hsp70-based system in the cell.
PMID- 29343245
TI - An unusual case of symptomatic deep vein thrombosis and pulmonary embolism after
arthroscopic meniscus surgery.
AB - BACKGROUND: Although thrombosis complication is rare after arthroscopic meniscus
surgery, deep vein thrombosis and pulmonary embolism can be fatal. The associated
risk factors and whether anticoagulant prevention after arthroscopic knee surgery
is necessary have not reach consensus. Here we present a case of deep vein
thrombosis and pulmonary embolism after a common arthroscopic meniscectomy. CASE
PRESENTATION: The patient had no risk factors except ipsilateral leg varicose
veins. She present swell at knee and calf from postoperative 3 weeks, and
developed dyspnea, palpitation, and nausea on 33th day, pulmonary embolism was
confirmed with CT angiography at emergency department. After thrombolysis and
anticoagulation therapy were administered, the patient improved well and
discharged. And the intravenous ultrasound confirmed thrombosis of popliteal vein
and small saphenous vein. Who don't have common risk factors for venous
thromboembolism. CONCLUSIONS: Despite the low incidence of thromboembolic
complications after simple arthroscopy surgery, its life-threatening and
devastating property make clinicians rethink the necessity of thromboprophylaxis
and importance of preoperative relative risk factors screening.
PMID- 29343246
TI - Influence of preoperative life satisfaction on recovery and outcomes after
colorectal cancer surgery - a prospective pilot study.
AB - BACKGROUND: Colorectal surgery has an important impact on a patient's quality of
life, and postoperative rehabilitation shows large variations. To enhance the
understanding of recovery after colorectal cancer, health-related quality of life
has become a standard outcome measurement for clinical care and research.
Therefore, we aimed to correlate the influence of preoperative global life
satisfaction on subjective feelings of well-being with clinical outcomes after
colorectal surgery. METHODS: In this pilot study of consecutive colorectal
surgery patients, various dimensions of feelings of preoperative life
satisfaction were assessed using a self-rated scale, which was validated in
French. Both objective (length of stay and complications) and subjective (pain,
subjective well-being and quality of sleep) indicators of recovery were evaluated
daily during each patient's hospital stay. RESULTS: A total of 112 patients were
included. The results showed a negative relationship between life satisfaction
and postoperative complications and a significant negative correlation with the
length of stay. Moreover, a significant positive correlation between life
satisfaction and the combined subjective indicators of recovery was observed.
CONCLUSION: We have shown the importance of positive preoperative mental states
and global life satisfaction as characteristics that are associated with an
improved recovery after colorectal surgery. Therefore, patients with a good level
of life satisfaction may be better able to face the consequences of colorectal
surgery, which is a relevant parameter in supportive cancer care.
PMID- 29343247
TI - Consumption of sugar-sweetened beverages and artificially sweetened beverages
from childhood to adulthood in relation to socioeconomic status - 15 years follow
up in Norway.
AB - BACKGROUND: In Norway, social inequalities in health and health-related behaviors
have been reported despite the well-developed welfare state. The objective of the
present study was to analyze; (i) the development in frequency of consumption of
sugar-sweetened beverages (SSB) and artificially sweetened beverages (ASB) from
childhood to adulthood; (ii) socioeconomic inequalities in the consumption of SSB
and ASB using different indicators of socioeconomic status (SES); (iii) time
trends in potential disparities in SSB and ASB consumption among different
socioeconomic groups to assess the development in socioeconomic inequality from
childhood to adulthood. METHODS: This study uses data from the Fruits and
Vegetables Make the Marks (FVMM) longitudinal cohort, including participants (n =
437) from 20 random schools from two Norwegian counties. Data from the first
survey in 2001 (mean age 11.8) and follow-up surveys in 2005 (mean age 15.5) and
2016 (mean age 26.5) were used. Consumption of SSB and ASB were measured using a
food frequency questionnaire, which the participants completed at school in 2001
and 2005, and online in 2016. Various indicators of SES were included; in 2001,
parental education and income were measured, in 2005, participants' educational
intentions in adolescence were measured, and in 2016, participants' own education
and income were measured. The main analyses conducted were linear mixed effects
analysis of the repeated measures. RESULTS: Between 2001 and 2016, a decrease in
frequency of consumption of SSB (2.8 v 1.3 times/week; p = < 0.001) and an
increase in frequency of consumption of ASB (1.1 v 1.6 times/week; p = 0.002)
were observed. Participants with a higher educational level in adulthood and
higher educational intentions in adolescence had a significantly lower frequency
of consumption of SSB at all time points (2001, 2005 and 2016). No significant
widening (or narrowing) of inequalities were observed from childhood to
adulthood. CONCLUSIONS: A decrease in consumption of SSB and an increase in
consumption of ASB from childhood to adulthood were found. Participants with high
SES consumed in general less SSB (but not ASB), however, results varied depending
on SES indicator used. The established inequalities persisted from childhood to
adulthood.
PMID- 29343248
TI - Minimally invasive versus open Transforaminal lumbar Interbody fusion in obese
patients: a meta-analysis.
AB - BACKGROUND: Minimally invasive transforaminal lumbar interbody fusion (MI-TLIF)
has been employed in increasing cases compared with open TLIF (Open-TLIF).
However, it is uncertain whether the advantages of MI-TLIF can also be
specifically applied in obese patients. Therefore, the current study was thereby
carried out aiming to compare the outcomes of MI-TLIF with those of Open-TLIF in
obese patients with lumbar degenerative diseases. METHODS: Electronic databases
were systemically retrieved from construction to May 2017. Meanwhile, the odds
ratio (OR), mean difference (MD) and 95% confidence intervals (CI) were
determined. RESULTS: A total of 7 observational cohort studies were enrolled into
the current meta-analysis. The results indicated that, compared with Open-TLIF
group, MI-TLIF could remarkably reduce the operative time (P = 0.002),
intraoperative blood loss (P < 0.001), postoperative drainage (P = 0.01), length
of stay (P < 0.001) and incidence of complications (P < 0.001). In addition, MI
TLIF could also lead to markedly lower early back pain-Visual Analog Scale (BP
VAS) score than that of Open-TLIF (P < 0.001), but no statistically significant
differences were found in Oswestry Disability Index (ODI), late BP-VAS, early leg
pain-VAS (LP-VAS) and late LP-VAS scores. CONCLUSION: MI-TLIF may be a more
preferred choice for obese patients undergoing spinal surgery. However,
differences in the long-term functional and pain outcomes between MI-TLIF and
Open-TLIF remain a source of controversy, which should be further verified in
future randomized-control trials.
PMID- 29343249
TI - microRNA-124 inhibits bone metastasis of breast cancer by repressing Interleukin
11.
AB - BACKGROUND: Most patients with breast cancer in advanced stages of the disease
suffer from bone metastases which lead to fractures and nerve compression
syndromes. microRNA dysregulation is an important event in the metastases of
breast cancer to bone. microRNA-124 (miR-124) has been proved to inhibit cancer
progression, whereas its effect on bone metastases of breast cancer has not been
reported. Therefore, this study aimed to investigate the role and underlying
mechanism of miR-124 in bone metastases of breast cancer. METHODS: In situ
hybridization (ISH) was used to detect the expression of miR-124 in breast cancer
tissues and bone metastatic tissues. Ventricle injection model was constructed to
explore the effect of miR-124 on bone metastasis in vivo. The function of cancer
cell derived miR-124 in the differentiation of osteoclast progenitor cells was
verified in vitro. Dual-luciferase reporter assay was conducted to confirm
Interleukin-11 (IL-11) as a miR-124 target. The involvement of miR-124/IL-11 in
the prognosis of breast cancer patients with bone metastasis was determined by
Kaplan-Meier analysis. RESULTS: Herein, we found that miR-124 was significantly
reduced in metastatic bone tissues from breast cancers. Down-regulation of miR
124 was associated with aggressive clinical characteristics and shorter bone
metastasis-free survival and overall survival. Restoration of miR-124 suppressed,
while inhibition of miR-124 promoted the bone metastasis of breast cancer cells
in vivo. At the cellular level, gain of function and loss-of function assays
indicated that cancer cell-derived miR-124 inhibited the survival and
differentiation of osteoclast progenitor cells. At the molecular level, we
demonstrated that IL-11 partially mediated osteoclastogenesis suppression by miR
124 using in vitro and in vivo assays. Furthermore, IL-11 levels were inversely
correlated with miR-124, and up-regulation IL-11 in bone metastases was
associated with a poor prognosis. CONCLUSIONS: Thus, the identification of a
dysregulated miR-124/IL-11 axis helps elucidate mechanisms of breast cancer
metastases to bone, uncovers new prognostic markers, and facilitates the
development of novel therapeutic targets to treat and even prevent bone
metastases of breast cancer.
PMID- 29343250
TI - Evaluation of health status in patients with hepatitis c treated with and without
interferon.
AB - BACKGROUND: The evolution of technology in healthcare has increased the health
care's costs and, the universal healthcare systems, in developed countries, need
to ensure proper allocation of resources. Thus, the major issue is assessing the
effectiveness of new medical technologies. The evaluation of quality of life in
response to new treatments has become a key indicator in chronic conditions for
which medical interventions are evaluated not only in terms of increasing the
number of expected life years but also in terms of increasing quality of life.
The aim of this observational study was to verify whether a simple instrument (EQ
5D-5 L) can capture variations in health-related quality of life (HRQoL) and
allow us to evaluate the impact of different drug treatment protocols in patients
with hepatitis C virus (HCV) on daily activities. METHODS: Sixty six patients
with HCV were consecutively enrolled in the Hepatology Unit at the University
Hospital of Catania "G. Rodolico". Sixteen patients received new direct-acting
antiviral agents (DAAs) plus pegylated alpha interferon (Peg-alpha-IFN) protocol
(Group A) and 50 DAAs IFN free protocol (Group B). The EQ-5D-5 L(r) questionnaire
and visual analog scale (VAS) were given to both groups to calculate
coefficient's utility. We used the EQ-5D-5 L Crosswalk Index Value Calculator to
obtain the utility EQIndex and both parametric and non parametric tests for the
statistical analysis. RESULTS: The biopsy taken at the beginning of treatment
showed comparable cell damage in both groups. The difference in the VAS results
was negative for patients who received protocols containing IFN (indicating
decreased quality of life),whereas it was positive in patients treated with IFN
free protocols. The baseline EQIndex did not reveal any differences between the
two treatment groups. The post-treatment EQIndex was statistically better in the
groups that received IFN-free therapy. CONCLUSIONS: When innovative treatments
are introduced into clinical practice, assessing quality of life is mandatory to
determine their benefits. The instruments used in the present study are effective
in detecting the areas in which improvement has occurred. These instruments can
be easily managed by general practitioners for follow up of progression of the
disease and referred to the specialist.
PMID- 29343251
TI - Effects of the isoflavone genistein in early life stages of the Senegalese sole,
Solea senegalensis: role of the Survivin and proliferation versus apoptosis
pathways.
AB - BACKGROUND: Phytochemical flavonoids are widely distributed in the environment
and are derived from many anthropogenic activities. The isoflavone genistein is a
naturally occurring compound found in soya products that are habitual
constituents of the aquafeeds. This isoflavone possesses oestrogenic biological
activity and also apoptotic properties. The present study has been performed to
determine the effects of the genistein in the early life stages of the flatfish
Senegalese sole during the first month of larval life, and it is focused
especially at the metamorphosis, analysing the expression transcript levels and
the immunohistochemical protein patterns implicated in the cell proliferation and
apoptosis pathways (proliferation cellular/PCNA, anti-apoptosis Survivin/BIRC-5,
death receptors/Fas, and Caspases). RESULTS: The isoflavone genistein induced
some temporal disrupting effects in several pro-apoptotic signalling pathways
(Fas, CASP-6) at both genistein doses (3 mg/L and 10 mg/L), with increased Fas
transcripts and also decreasing CASP-6 mRNA expression levels during metamorphic
and post-metamorphic stages of the Senegalese sole. On the other hand, the anti
apoptotic BIRC-5 expression levels were weakly down-regulated with both the
highest and lowest doses, but all of these imbalances were stabilised to the
baseline levels. In early life stages of the controls, the constitutive basal
transcript levels were temporarily and differentially expressed, reaching the
highest levels at the pre-metamorphosis phase, as especially in endotrophic
larvae (i.e. BIRC-5 mRNA), as well as in the metamorphic (i.e. CASP-6 mRNA) and
post-metamorphic stages (i.e. Fas mRNA). In general, through development,
continuous and progressive increases in the protein patterns of cell
proliferation-PCNA (e.g. mitotic nuclei), anti-apoptotic Survivin (e.g.
haematopoietic system, brain, digestive system, gills) and CASP-2 and -6 (e.g.
brain, gills, kidney, digestive system, vascular systems, among others) have been
immunohistochemically detected. Besides, both the controls and genistein exposed
larvae displayed parallel immunostaining protein patterns in the different organ
systems and tissues. CONCLUSIONS: The transcriptional imbalances observed in the
studied genes (BIRC-5, CASP-6, Fas) were only temporarily induced, and apparently
no changes in the immunohistochemical protein patterns were detected. Thus, the
isoflavone genistein caused not harmful effects in the development and
metamorphosis of the Senegalese sole exposed to chronic environmentally relevant
concentrations (3 and 10 mg/L).
PMID- 29343252
TI - Insights into the genetics of blood pressure in black South African individuals:
the Birth to Twenty cohort.
AB - BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of non
communicable disease deaths globally, with hypertension being a major risk factor
contributing to CVDs. Blood pressure is a heritable trait, with relatively few
genetic studies having been performed in Africans. This study aimed to identify
genetic variants associated with variance in systolic (SBP) and diastolic (DBP)
blood pressure in black South Africans. METHODS: Genotyping was performed using
the Metabochip in a subset of participants (mixed sex; median age 17.9) and their
adult female caregivers (median age 41.0) from the Birth to Twenty cohort (n =
1947). Data were analysed as a merged dataset (all participants and caregivers
together) in GEMMA (v0.94.1) using univariate linear mixed models, incorporating
a centered relatedness matrix to account for the relatedness between individuals
and with adjustments for age, sex, BMI and principal components of the genotype
information. RESULTS: Association analysis identified regions of interest in the
NOS1AP (DBP: rs112468105 - p = 7.18 * 10-5 and SBP: rs4657181 - p = 4.04 * 10-5),
MYRF (SBP: rs11230796 - p = 2.16 * 10-7, rs400075 - p = 2.88 * 10-7) and POC1B
(SBP: rs770373 - p = 7.05 * 10-5, rs770374 - p = 9.05 * 10-5) genes and some
intergenic regions (DACH1|LOC440145 (DBP: rs17240498 - p = 4.91 * 10-6 and SBP:
rs17240498 - p = 2.10 * 10-5) and INTS10|LPL (SBP: rs55830938 - p = 1.30 * 10-5,
rs73599609 - p = 5.78 * 10-5, rs73667448 - p = 6.86 * 10-5)). CONCLUSIONS: The
study provided further insight into the contribution of genetic variants to blood
pressure in black South Africans. Future functional and replication studies in
larger samples are required to confirm the role of the identified loci in blood
pressure regulation and whether or not these variants are African-specific.
PMID- 29343253
TI - An integrated primary care approach for frail community-dwelling older persons: a
step forward in improving the quality of care.
AB - BACKGROUND: High-quality care delivery for frail older persons, many of whom have
multiple complex needs, is among the greatest challenges faced by healthcare
systems today. The Chronic Care Model (CCM) may guide quality improvement efforts
for primary care delivery to frail older populations. Objectives of this study
were to assess the implementation of interventions in CCM dimensions, and to
investigate the quality of primary care as perceived by healthcare professionals,
in practices following the Finding and Follow-up of Frail older persons (FFF)
integrated care approach and those providing usual care. METHODS: Structured
interviews were conducted with general practitioners (GPs) from 11 intervention
practices and 4 control practices to assess the implementation of interventions.
A longitudinal survey (12-month period, 2 measurement timepoints) was conducted
to assess the quality of primary care as perceived by healthcare professionals
(intervention and control GP practices) using the Assessment of Chronic Illness
Care Short version (ACIC-S). Independent-samples t-tests were used to assess
differences in ACIC-S scores between groups. Interviews were conducted with GPs
from the intervention practices to gain a deeper understanding of their
experiences with the FFF approach. RESULTS: Intervention practices implemented
significantly more interventions congruent with (dimensions of) the CCM compared
with control GP practices. With respect to the quality of primary care as
perceived by healthcare professionals, mean ACIC-S scores for all CCM dimensions
and overall mean ACIC-S scores were significantly higher in the intervention
group than in the control group at the follow-up timepoint. The number of
implemented interventions was associated positively with perceived quality of
primary care (ACIC-S scores) at follow-up. Important motives of GPs to implement
the FFF approach were the aging of the population and transformations in the
primary care sector. Proactive care delivery and multidisciplinary collaboration
were considered to be essential. Major challenges to the implementation and
embedding of the FFF approach were structural financing and manpower, and the
availability of a facilitating information and communication technology system.
CONCLUSIONS: Our study showed that proactive, integrated care that is based on
(elements of) the CCM may be a step forward in improving quality of care for
frail older persons.
PMID- 29343254
TI - Knowledge of cervical cancer and Pap smear among Uyghur women from Xinjiang,
China.
AB - BACKGROUND: Cervical cancer is a significant public health issue in Xinjiang
China. In order to provide scientific basis for cervical cancer intervention in
Xinjiang, women's knowledge of cervical cancer was investigated in this study.
Besides, relations between Uyghur women's awareness and their age, educational
background, yearly household were evaluated. METHODS: Questionnaire survey was
conducted to 7100 Uyghur women from Karkax Hotan and Payzivat Kashgar during 2008
and 2009. Women aged 21 to 70 years, had sexual activity, no history of cervical
lesion or cervical cancer were considered to be eligible to the study.
Information include participants' socio-demographic background, personal data,
awareness about Pap smear, about cervical cancer and HPV, sources of information
acquisition was investigated. RESULTS: 65.1% of the 7100 respondents with primary
education level, and 95.0% participants were farmers. Only 7.4% had undertaken
Pap smears before, not aware of the importance of the test (97.4% of 7100) was
the main reason for not performing Pap smears. 29.3% of total participants had
heard about cervical cancer, and only 0.14% (10 out of 7100) had heard about HPV.
Top three route of knowledge acquire were television advertises (39.1%),
neighbors (21.0%) and health care providers (15.0%). Women younger than 40 years,
with higher educational levels and higher income had better awareness of cervical
cancer and more willing to accept regular Pap smears. CONCLUSIONS: Uyghur women
in Xinjiang had poor knowledge of cervical cancer and HPV infection. Low
awareness of women was associated with less household income and lower
educational levels. TV shows and education from health care providers may
increase women's participation in cervical cancer control and prevention.
PMID- 29343255
TI - Inducible HIV RNA transcription assays to measure HIV persistence: pros and cons
of a compromise.
AB - With the increasing number of therapeutic strategies tested in humans to reduce
the size of the latent reservoir, the development of a robust, precise and
clinical trial scalable assay that measures the frequency of infected cells
carrying inducible replication-competent HIV is urgently needed. The size of the
pool of cells carrying replication-competent HIV is largely overestimated by DNA
assays, as a result of a large proportion of defective viruses, and
underestimated by co-culture outgrowth assays. New culture methods that measure
the inducible HIV reservoir have been developed during the past few years. In
these induction assays, CD4+ T cells from virally suppressed individuals are
activated and HIV RNA is measured in cell extracts or cell supernatants. In this
review, we summarize the principle and outcomes of these assays and discuss the
potential of these methods in the evaluation of HIV eradication strategies.
PMID- 29343256
TI - The effects of green cardamom supplementation on blood glucose, lipids profile,
oxidative stress, sirtuin-1 and irisin in type 2 diabetic patients: a study
protocol for a randomized placebo-controlled clinical trial.
AB - BACKGROUND: It has been suggested that the antioxidant, anti-inflammatory and
hypolipidemic activities of cardamom may improve diabetes. However, the effect of
this spice has not been investigated in diabetic subjects. This study was planned
to determine the effects of green cardamom on blood glucose, lipids and oxidative
stress status in type 2 diabetic patients. METHODS/DESIGN: Eighty overweight or
obese patients with type 2 diabetes will be selected. They will be randomly
assigned to receive 3 g/d green cardamom or placebo for 10 weeks. The socio
demographic, physical activity and 24-h food recall questionnaires will be
collected for each subject. Weight, height and waist circumference will be
measured. Determination of blood glucose, lipid profile, and oxidative stress
biomarkers including serum levels of total antioxidant capacity (TAC),
malondialdehyde (MDA), and glutathione peroxidase (GPx) and superoxide dismutase
(SOD) in red blood cells will be performed. The homeostasis model assessment
estimated insulin resistance (HOMA-IR) index and the quantitative insulin
sensitivity check index (QUICKI) will be calculated. Also, serum levels of
irisin, and Sirtuin1 (SIRT1) will be measured. DISCUSSION: This trial will be the
first study to explore the effects of green cardamom supplementation on glycemic
control, lipid profile and oxidative stress in patients with type 2 diabetes
mellitus. The results from this trial will provide evidence on the efficacy of
green cardamom in type 2 diabetes mellitus. TRIAL REGISTRATION NUMBER: (
http://www.irct.ir , identifier: IRCT2016042717254N5), Registration date:
23.11.2016.
PMID- 29343257
TI - Pigmented villonodular synovitis in pediatric population: review of literature
and a case report.
AB - BACKGROUND: Pigmented villonodular synovitis (PVNS) is a rare proliferative
process in children that mostly affects the knee joint. CASE PRESENTATION: The
study follows the case of a 3-year-old boy presenting recurrent patellar
dislocation and PVNS. Due to symptoms such as chronic arthritis, he had been
taking prednisolone and methotrexate for 6 months before receiving a definitive
diagnosis. After a period of showing no improvements from his treatment, he was
referred to our center and was diagnosed with local PVNS using magnetic resonance
imaging (MRI). The patient was treated for his patellar dislocation by way of
open synovectomy, lateral retinacular release, and a proximal realignment
procedure, with no recurrence after a 24-month follow-up. CONCLUSION: PVNS may
appear with symptoms resembling juvenile idiopathic arthritis, thus the disease
should be considered in differential diagnosis of any inflammatory arthritis in
children. PVNS may also cause mechanical symptoms such as patellar dislocation.
In addition to synovectomy, a realignment procedure can be a useful method of
treatment.
PMID- 29343258
TI - Mass-spectrometric profiling of cerebrospinal fluid reveals metabolite biomarkers
for CNS involvement in varicella zoster virus reactivation.
AB - BACKGROUND: Varicella zoster virus (VZV) reactivation spans the spectrum from
uncomplicated segmental herpes zoster to life-threatening disseminated CNS
infection. Moreover, in the absence of a small animal model for this human
pathogen, studies of pathogenesis at the organismal level depend on analysis of
human biosamples. Changes in cerebrospinal fluid (CSF) metabolites may reflect
critical aspects of host responses and end-organ damage in neuroinfection and
neuroinflammation. We therefore applied a targeted metabolomics screen of CSF to
three clinically distinct forms of VZV reactivation and infectious and non
infectious disease controls in order to identify biomarkers for CNS involvement
in VZV reactivation. METHODS: Metabolite profiles were determined by targeted
liquid chromatography-mass spectrometry in CSF from patients with segmental
zoster (shingles, n = 14), facial nerve zoster (n = 16), VZV
meningitis/encephalitis (n = 15), enteroviral meningitis (n = 10), idiopathic
Bell's palsy (n = 11), and normal pressure hydrocephalus (n = 15). RESULTS:
Concentrations of 88 metabolites passing quality assessment clearly separated the
three VZV reactivation forms from each other and from the non-infected samples.
Internal cross-validation identified four metabolites (SM C16:1, glycine, lysoPC
a C26:1, PC ae C34:0) that were particularly associated with VZV
meningoencephalitis. SM(OH) C14:1 accurately distinguished facial nerve zoster
from Bell's palsy. Random forest construction revealed even more accurate
classifiers (signatures comprising 2-4 metabolites) for most comparisons. Some of
the most accurate biomarkers correlated only weakly with CSF leukocyte count,
indicating that they do not merely reflect recruitment of inflammatory cells but,
rather, specific pathophysiological mechanisms. Across all samples, only the sum
of hexoses and the amino acids arginine, serine, and tryptophan correlated
negatively with leukocyte count. Increased expression of the metabolites
associated with VZV meningoencephalitis could be linked to processes relating to
neuroinflammation/immune activation, neuronal signaling, and cell stress,
turnover, and death (e.g., autophagy and apoptosis), suggesting that these
metabolites might sense processes relating to end-organ damage. CONCLUSIONS: The
results provide proof-of-concept for the value of CSF metabolites as (1) disease
associated signatures suggesting pathophysiological mechanisms, (2) degree and
nature of neuroinflammation, and (3) biomarkers for diagnosis and risk
stratification of VZV reactivation and, likely, neuroinfections due to other
pathogens. TRIAL REGISTRATION: Not applicable (non-interventional study).
PMID- 29343259
TI - Influence of apocynin on cardiac remodeling in rats with streptozotocin-induced
diabetes mellitus.
AB - BACKGROUND: Increased reactive oxygen species (ROS) generation in diabetes
mellitus (DM) is an important mechanism leading to diabetic cardiomyopathy.
Apocynin, a drug isolated from the herb Picrorhiza kurroa, is considered an
antioxidant agent by inhibiting NADPH oxidase activity and improving ROS
scavenging. This study analyzed the influence of apocynin on cardiac remodeling
in diabetic rats. METHODS: Six-month-old male Wistar rats were assigned into 4
groups: control (CTL, n = 15), control + apocynin (CTL + APO, n = 20), diabetes
(DM, n = 20), and diabetes + apocynin (DM + APO, n = 20). DM was induced by
streptozotocin. Seven days later, apocynin (16 mg/kg/day) or vehicle was
initiated and maintained for 8 weeks. Left ventricular (LV) histological sections
were used to analyze interstitial collagen fraction. NADPH oxidase activity was
evaluated in LV samples. Comparisons between groups were performed by ANOVA for a
2 * 2 factorial design followed by the Bonferroni post hoc test. RESULTS: Body
weight (BW) was lower and glycemia higher in diabetic animals. Echocardiogram
showed increased left atrial diameter, LV diastolic diameter, and LV mass indexed
by BW in both diabetic groups; apocynin did not affect these indices. LV systolic
function was impaired in DM groups and unchanged by apocynin. Isovolumic
relaxation time was increased in DM groups; transmitral E/A ratio was higher in
DM + APO compared to DM. Myocardial functional evaluation through papillary
muscle preparations showed impaired contractile and relaxation function in both
DM groups at baseline conditions. After positive inotropic stimulation, developed
tension (DT) was lower in DM than CTL. In DM + APO, DT had values between those
in DM and CTL + APO and did not significantly differ from either group.
Myocardial interstitial collagen fraction was higher in DM than CTL and did not
differ between DM + APO and CTL + APO. Serum activity of antioxidant enzymes
glutathione peroxidase, superoxide dismutase (SOD), and catalase was lower in DM
than CTL; apocynin restored catalase and SOD levels in DM + APO. Myocardial NADPH
oxidase activity did not differ between groups. CONCLUSION: Apocynin restores
serum antioxidant enzyme activity despite unchanged myocardial NADPH oxidase
activity in diabetic rats.
PMID- 29343261
TI - Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances and childhood
atopic dermatitis: a prospective birth cohort study.
AB - BACKGROUND: Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been
reported to suppress immune function. However, previous studies on prenatal
exposure to PFASs and allergic disorders in offspring provided inconsistent
results. We aimed to examine the association between prenatal exposure to PFASs
and childhood atopic dermatitis (AD) in offspring up to 24 months of age.
METHODS: A prospective birth cohort study involving 1056 pregnant women was
conducted in two hospitals in Shanghai from 2012 to 2015. Prenatal information
was collected by an interview with the women and from medical records. Fetal
umbilical cord blood was collected at birth. Cord blood plasma PFASs were
measured. Children were followed at 6, 12 and 24 months and information on the
development of AD was recorded. AD was diagnosed by 2 dermatologists
independently based on the questionnaires. Multiple logistic regression was used
to compute odds ratio (OR) and corresponding 95% confidence interval (CI) for the
association between AD and each PFASs, adjusting for potential confounders.
RESULTS: A total of 687 children completed a 2-year follow-up visit and had PFASs
measurement. AD was diagnosed in 173 (25.2%) children during the first 24 months.
In female children, a log-unit increase in perfluorooctanoic acid (PFOA) was
associated with a 2.1-fold increase in AD risk (AOR 2.07, 95% CI 1.13-3.80) after
adjusting for potential confounders. The corresponding risk was 2.22 (1.07-4.58)
for perfluorononanoic acid (PFNA). The highest PFOA quartile was significantly
associated with AD (2.52, 1.12-5.68) compared with the lowest quartile. The
highest quartile of PFNA, perfluorodecanoic acid (PFDA) and perfluorohexane
sulfonic acid (PFHxS) were associated with AD with AOR (95% CI) being 2.14 (0.97
4.74), 2.14 (1.00-4.57), and 2.30 (1.03-5.15), respectively. Additionally, the
second quartile of perfluorododecanoic acid (PFDoA) was associated with a 3.2
fold increase in AD risk (3.24, 1.44-7.27). However, no significant associations
were found in male children. CONCLUSIONS: Prenatal exposure to PFOA, PFDA, PFDoA
and PFHxS significantly increased the risk of childhood AD in female children
during the first 24 months of life. In addition, the associations between AD with
prenatal exposure to PFNA were close to statistical significance.
PMID- 29343260
TI - Liquid biomarkers in melanoma: detection and discovery.
AB - A vast array of tumor-derived genetic, proteomic and cellular components are
constantly released into the circulation of cancer patients. These molecules
including circulating tumor DNA and RNA, proteins, tumor and immune cells are
emerging as convenient and accurate liquid biomarkers of cancer. Circulating
cancer biomarkers provide invaluable information on cancer detection and
diagnosis, prognosticate patient outcomes, and predict treatment response. In
this era of effective molecular targeted treatments and immunotherapies, there is
now an urgent need to implement use of these circulating biomarkers in the clinic
to facilitate personalized therapy. In this review, we present recent findings in
circulating melanoma biomarkers, examine the challenges and promise of evolving
technologies used for liquid biomarker discovery, and discuss future directions
and perspectives in melanoma biomarker research.
PMID- 29343262
TI - What motivates medical students to select medical studies: a systematic
literature review.
AB - BACKGROUND: There is a significant shortage of health workers across and within
countries. It is of utmost importance to determine the factors that motivate
students to opt for medical studies. The objective of this study is to group and
review all the studies that investigated the motivational factors that underpin
students' selection of medical study in recent years. METHODS: The literature
search was carried out by two researchers independently in PubMed, Google
Scholar, Wiley and IndMED databases for articles published from year 2006 till
2016. A total of 38 combinations of MeSH words were used for search purpose.
Studies related to medical students and interns have been included. The
application of inclusion and exclusion criteria and PRISMA guidelines for
reporting systematic review led to the final selection of 24 articles. RESULTS:
The majority of the studies (n = 16; 66.6%) were from high-income countries
followed by an equal number from upper-middle and lower-middle income countries
(n = 4,16.7%). None of the studies were from low-income countries. All of the
studies were cross-sectional in nature. The main motivating factors that emerged
were scientific (interest in science / medicine, social interest and academia,
flexible work hours and work independence), societal (prestige, job security,
financial security) and humanitarian (serving the poor and under priviledged) in
high-, upper-middle and lower-middle income countries, respectively. The findings
were comparable to Maslow's hierarchy of needs theory of motivation. CONCLUSION:
This systematic review identifies the motivational factors influencing students
to join medical studies in different parts of the globe. These factors vary per
country depending on the level of income. This study offers cues to policy makers
and educators to formulate policy in order to tackle the shortage of health
workers, i.e. medical doctors. However, more research is needed to translate
health policy into concrete and effective measures.
PMID- 29343263
TI - Knowledge, use, and disuse of unconventional food plants.
AB - BACKGROUND: People's diets are usually restricted to a small number of plant
species, even in regions with great diversity. We investigated the knowledge of
residents in Ribeirao da Ilha, a district of Florianopolis (Santa Catarina,
Brazil), about unconventional food plants (UFP). We report the UFP of the region,
the parts used, the methods of processing, and the reasons for reduced use or
even lack of use. METHODS: From June 2014 to January 2015, we interviewed 26 long
established residents and made free listings of plant resources in the region. We
also did three guided tours, and 24 residents (among the 26) checked pictures of
the mentioned plants in order to identify them. RESULTS: We identified 63 species
distributed in 25 botanical families. Half of the species were mentioned only by
one informant. The fruit was the most frequently used part (80% of citations),
consumed mainly without processing. Among those species, 27% were used
exclusively in the past. The residents attributed non-use to the difficulty in
locating the plants and loss of interest in the resource. CONCLUSION:
Urbanization and environmental restrictions contribute to the difficulty of
access to UFP. Encouraging residents to continue using UFP is necessary to
perpetuate this threatened knowledge, promote a more diversified and healthier
diet, stimulate a greater interaction among people and nature, and promote on
farm conservation of edible plants.
PMID- 29343265
TI - RNase If -treated quantitative PCR for dsRNA quantitation of RNAi trait in
genetically modified crops.
AB - BACKGROUND: RNA interference (RNAi) technology has been widely used to knockdown
target genes via post-transcriptional silencing. In plants, RNAi is used as an
effective tool with diverse applications being developed such as resistance
against insects, fungi, viruses, and metabolism manipulation. To develop
genetically modified (GM) RNAi traits for insect control, a transgene is created
and composed of an inversely-repeated sequence of the target gene with a spacer
region inserted between the repeats. The transgene design is subject to form a
self-complementary hairpin RNA (hpRNA) and the active molecules are > 60 bp
doubled-stranded RNA (dsRNA) derived from the hpRNA. However, in some cases, an
undesirable intermediate such as single-stranded RNA (ssRNA) may be formed, which
is not an active molecule. The aforementioned characteristics of RNAi traits lead
to increase the challenges for RNAi-derived dsRNA quantitation. RESULTS: To
quantify the dsRNA and distinguish it from the ssRNA in transgenic maize, an
analytical tool is required to be able to effectively quantify dsRNA which
contains a strong secondary structure. Herein, we develop a modified qRT-PCR
method (abbreviated as RNase If -qPCR) coupled with a ssRNA preferred
endonuclease (i.e., RNase If). This method enables the precise measurement of the
active molecules (i.e., dsRNA) derived from RNAi traits of GM crops and
separately quantifies the dsRNA from ssRNA. Notably, we also demonstrate that the
RNase If -qPCR is comparable to a hybridization-based method (Quantigene Plex
2.0). CONCLUSIONS: To our best knowledge, this is the first report of a method
combining RNase If with modified qRT-PCR protocol. The method represents a
reliable analytical tool to quantify dsRNA for GM RNAi crops. It provides a cost
effective and feasible analytical tool for general molecular laboratory without
using additional equipment for other methods. The RNase If -qPCR method
demonstrates high sensitivity (to 0.001 pg/ MUL of dsRNA), precision and
accuracy. In this report, we demonstrated the deployment of this method to
characterize the RNAi events carrying v-ATPase C in maize during trait
development process. The method can be utilized in any application which requires
the dsRNA quantification such as double-stranded RNA virus or sprayable dsRNA as
herbicide.
PMID- 29343264
TI - Associations between circulating adipokines and bone mineral density in patients
with knee osteoarthritis: a cross-sectional study.
AB - BACKGROUND: Associations between adipokines and bone mineral density (BMD) in
knee osteoarthritis (OA) remain indistinct. The aim of this study was to
investigate the cross-sectional associations between serum levels of adipokines
and BMD in patients with knee OA. METHODS: This study included 164 patients with
symptomatic knee OA from the Anhui Osteoarthritis study. Serum levels of leptin,
adiponectin, and resistin were measured using an enzyme-linked immunosorbent
assay (ELISA). BMD at total body, spine, hip, and femur were measured by dual
energy X-ray absorptiometry (DXA). RESULTS: In multivariable analyses, serum
levels of leptin were significantly associated with reduced BMD at total body,
hip, total femur, femoral neck, and femoral shaft (beta = - 0.019, 95% CI -0.034
to - 0.005; beta = - 0.018, 95% CI -0.034 to - 0.003; beta = - 0.018, 95% CI
0.034 to - 0.002; beta = - 0.016, 95% CI -0.032 to 0.000; beta = - 0.026, 95% CI
0.046 to - 0.006; respectively). Serum levels of adiponectin were significantly
and negatively associated with BMD at total femur and femoral shaft (beta = -
0.007, 95% CI -0.013 to 0.000; beta = - 0.011, 95% CI -0.018 to - 0.003;
respectively). However, no significant associations were found between serum
levels of resistin and BMD at any site measured. CONCLUSIONS: Serum levels of
leptin and adiponectin were significantly and negatively associated with BMD,
suggesting potentially detrimental effects of leptin and adiponectin on BMD in
knee OA patients.
PMID- 29343266
TI - Identification of pain categories associated with change in pain in patients
receiving placebo: data from two phase 3 randomized clinical trials in
symptomatic knee osteoarthritis.
AB - BACKGROUND: Pain is the principal clinical symptom of osteoarthritis (OA), and
development of safe and effective analgesics for OA pain is needed. Drug
development of new analgesics for OA pain is impaired by substantial change in
pain in patients receiving placebo, and more data describing clinical
characteristics and pain categories particularly associated with this phenomenon
is needed. The purpose of this post-hoc analysis was to investigate clinical
characteristics and pain categories and their association with radiographic
progression and placebo pain reduction (PPR) in OA patients as measured the
Western Ontario and McMasters Arthritis (WOMAC). METHODS: Pooled data from the
placebo groups of two phase III randomized clinical trials in patients with knee
OA followed for 2 years were analyzed. Differences between individual sub-scores
and pain categories of weight-bearing and non-weight bearing pain over time were
assessed. Selected patient baseline characteristics were assessed for association
with PPR. Association between pain categories and radiographic progression was
analyzed. RESULTS: The reduction of pain in placebo-treated patients was
significantly higher in the composite of questions related to weight-bearing pain
compared to non-weight-bearing pain of the target knee. Baseline BMI, age and JSW
were not associated with pain change. Pain reduction was higher in the Target
knee, compared to the Non-Target knee at all corresponding time-points. A very
weak correlation was found between weight-bearing pain and progression in the non
target knee. CONCLUSIONS: These results indicate that the reduction in pain in
patients treated with placebo is significantly different between pain categories,
as weight-bearing pain was significantly more reduced compared to non-weight
bearing pain. Further research in pain categories in OA is warranted. TRIAL
REGISTRATION: NCT00486434 (trial 1) and NCT00704847 (trial 2).
PMID- 29343267
TI - TIPE2 suppresses progression and tumorigenesis of esophageal carcinoma via
inhibition of the Wnt/beta-catenin pathway.
AB - BACKGROUND: Esophageal carcinoma is the eighth prevalent malignancy and ranks the
sixth in carcinoma-related death worldwide. Tumor necrosis factor-alpha-induced
protein-8 like-2 (TIPE2) has been identified as a tumor suppressor in multiple
carcinomas. However, its roles and molecular mechanisms underlying esophageal
carcinoma progression are still undefined till now. METHODS: RT-qPCR assay was
employed to detect the expression of TIPE2 mRNA. TIPE2 protein expression was
measured by using western blot assay. Ad-V and Ad-TIPE2 adenoviruses were
constructed to overexpress TIPE2. The effects of TIPE2 overexpression on cell
proliferation, invasion and apoptosis were assessed by MTT and Edu incorporation
assays, transwell invasion assay and flow cytometry analysis, respectively. The
effect of TIPE2 overexpression on xenograft tumor growth was determined by
measuring tumor volume and weight, together with immunohistochemistry assay. The
effect of TIPE2 overexpression on the Wnt/beta-catenin signaling pathway was
evaluated by detecting the protein levels of beta-catenin, c-Myc and cyclinD1 in
EC9076 cells and xenograft tumors of esophageal carcinoma. RESULTS: TIPE2
expression was downregulated in esophageal carcinoma tissues and cells.
Adenovirus-mediated TIPE2 overexpression suppressed cell proliferation and
invasion, and induced apoptosis in esophageal carcinoma cells. Enforced
expression of TIPE2 inhibited tumor growth in vivo, as evidenced by the reduced
tumor volume, tumor weight and proliferating cell nuclear antigen expression.
Overexpression of TIPE2 inhibited the Wnt/beta-catenin signaling pathway in
esophageal carcinoma in vitro and in vivo. CONCLUSIONS: These results suggest
that TIPE2 suppressed progression and tumorigenesis of esophageal carcinoma via
inhibition of the Wnt/beta-catenin pathway.
PMID- 29343268
TI - Time-homogeneous Markov process for HIV/AIDS progression under a combination
treatment therapy: cohort study, South Africa.
AB - BACKGROUND: As HIV enters the human body, its main target is the CD4 cell which
it turns into a factory that produces millions of other HIV particles. These HIV
particles target new CD4 cells resulting in the progression of HIV infection to
AIDS. A continuous depletion of CD4 cells results in opportunistic infections,
for example tuberculosis (TB). The purpose of this study is to model and describe
the progression of HIV/AIDS disease in an individual on antiretroviral therapy
(ART) follow up using a continuous time homogeneous Markov process. A cohort of
319 HIV infected patients on ART follow up at a Wellness Clinic in Bela Bela,
South Africa is used in this study. Though Markov models based on CD4 cell counts
is a common approach in HIV/AIDS modelling, this paper is unique clinically in
that tuberculosis (TB) co-infection is included as a covariate. METHODS: The
method partitions the HIV infection period into five CD4-cell count intervals
followed by the end points; death, and withdrawal from study. The effectiveness
of treatment is analysed by comparing the forward transitions with the backward
transitions. The effects of reaction to treatment, TB co-infection, gender and
age on the transition rates are also examined. The developed models give very
good fit to the data. RESULTS: The results show that the strongest predictor of
transition from a state of CD4 cell count greater than 750 to a state of CD4
between 500 and 750 is a negative reaction to drug therapy. Development of TB
during the course of treatment is the greatest predictor of transitions to states
of lower CD4 cell count. Transitions from good states to bad states are higher on
male patients than their female counterparts. Patients in the cohort spend a
greater proportion of their total follow-up time in higher CD4 states.
CONCLUSION: From some of these findings we conclude that there is need to monitor
adverse reaction to drugs more frequently, screen HIV/AIDS patients for any signs
and symptoms of TB and check for factors that may explain gender differences
further.
PMID- 29343269
TI - Microglial activation mediates chronic mild stress-induced depressive- and
anxiety-like behavior in adult rats.
AB - BACKGROUND: Depression is a heterogeneous disorder, with the exact neuronal
mechanisms causing the disease yet to be discovered. Recent work suggests it is
accompanied by neuro-inflammation, characterized, in particular, by microglial
activation. However, microglial activation and its involvement in neuro
inflammation and stress-related depressive disorders are far from understood.
METHODS: We utilized multiple detection methods to detect the neuro-inflammation
in the hippocampus of rats after exposure to chronic mild stress (CMS). Male
Sprague Dawley (SD) rats were subjected to chronic mild stressors for 12 weeks.
Microglial activation and hippocampal neuro-inflammation were detected by using a
combinatory approach of in vivo [18F] DPA-714 positron emission computed
tomography (PET) imaging, ionized calcium-binding adapter molecule 1 and
translocator protein (TSPO) immunohistochemistry, and detection of NOD-like
receptor protein 3 (NLRP3) inflammasome and some inflammatory mediators. Then,
the rats were treated with minocycline during the last 4 weeks to observe its
effect on hippocampal neuro-inflammation and depressive-like behavior induced by
chronic mild stress. RESULTS: The results show that 12 weeks of chronic mild
stress induced remarkable depressive- and anxiety-like behavior, simultaneously
causing hippocampal microglial activation detected by PET, immunofluorescence
staining, and western blotting. Likewise, activation of NLRP3 inflammasome and
upregulation of inflammatory mediators, such as interleukin-1beta (IL-1beta), IL
6, and IL-18, were also observed in the hippocampus after exposure to chronic
stress. Interestingly, the anti-inflammatory mediators, such as IL-4 and IL-10,
were also increased in the hippocampus following chronic mild stress, which may
hint that chronic stress activates different types of microglia, which produce
pro-inflammatory cytokines or anti-inflammatory cytokines. Furthermore, chronic
minocycline treatment alleviated the depressive-like behavior induced by chronic
stress and significantly inhibited microglial activation. Similarly, the
activation of NLRP3 inflammasome and the increase of inflammatory mediators were
not exhibited or significantly less marked in the minocycline treatment group.
CONCLUSION: These results together indicate that microglial activation mediates
the chronic mild stress-induced depressive- and anxiety-like behavior and
hippocampal neuro-inflammation.
PMID- 29343271
TI - p66Shc gene expression in peripheral blood mononuclear cells and progression of
diabetic complications.
AB - BACKGROUND: The risk of diabetic complications is modified by genetic and
epigenetic factors. p66Shc drives the hyperglycaemic cell damage and its deletion
prevents experimental diabetic complications. We herein tested whether p66Shc
expression in peripheral blood mononuclear cells (PBMCs) predicts adverse
outcomes in people with diabetes. METHODS: In a cohort of 100 patients with
diabetes (16 type 1 and 84 type 2), we quantified baseline p66Shc expression in
PBMCs by quantitative PCR. Patients were extensively characterized for
demographics, anthropometrics, biochemical data, prevalence of complications, and
medications. With a pseudo-prospective design, we retrieved cardiovascular death,
major adverse cardiovascular events (MACE), and new occurrence of micro- or
macroangiopathy during follow-up. RESULTS: At baseline, patients were on average
60 year old, with 10-year diabetes duration, and overall poor glycaemic control
(HbA1c 7.8%). Patients with high versus low p66Shc expression (based on median
value) had very similar baseline characteristics. Average p66Shc expression did
not differ by presence/absence of complications. During a median 5.6-year follow
up, the primary endpoint of cardiovascular death or MACE occurred in 22 patients,
but no relation was detected between cardiovascular outcomes and p66Shc
expression. In patients who developed new complications at follow-up, baseline
p66Shc was significantly higher, especially for macroangiopathy. The incidence of
new macroangiopathy was > 3-times higher in patients with high versus those with
low baseline p66Shc expression. CONCLUSIONS: p66Shc expression in PBMCs was not
associated with prevalent diabetic complications but predicted new onset of
complications, especially macroangiopathy, although no relation with hard
cardiovascular endpoints was detected.
PMID- 29343270
TI - Isolation and characterization of olfactory ecto-mesenchymal stem cells from
eight mammalian genera.
AB - BACKGROUND: Stem cell-based therapies are an attractive option to promote
regeneration and repair defective tissues and organs. Thanks to their
multipotency, high proliferation rate and the lack of major ethical limitations,
"olfactory ecto-mesenchymal stem cells" (OE-MSCs) have been described as a
promising candidate to treat a variety of damaged tissues. Easily accessible in
the nasal cavity of most mammals, these cells are highly suitable for autologous
cell-based therapies and do not face issues associated with other stem cells.
However, their clinical use in humans and animals is limited due to a lack of
preclinical studies on autologous transplantation and because no well-established
methods currently exist to cultivate these cells. Here we evaluated the
feasibility of collecting, purifying and amplifying OE-MSCs from different
mammalian genera with the goal of promoting their interest in veterinary
regenerative medicine. Biopsies of olfactory mucosa from eight mammalian genera
(mouse, rat, rabbit, sheep, dog, horse, gray mouse lemur and macaque) were
collected, using techniques derived from those previously used in humans and
rats. The possibility of amplifying these cells and their stemness features and
differentiation capability were then evaluated. RESULTS: Biopsies were
successfully performed on olfactory mucosa without requiring the sacrifice of the
donor animal, except mice. Cell populations were rapidly generated from olfactory
mucosa explants. These cells displayed similar key features of their human
counterparts: a fibroblastic morphology, a robust expression of nestin, an
ability to form spheres and similar expression of surface markers (CD44, CD73).
Moreover, most of them also exhibited high proliferation rates and clonogenicity
with genus-specific properties. Finally, OE-MSCs also showed the ability to
differentiate into mesodermal lineages. CONCLUSIONS: This article describes for
the first time how millions of OE-MSCs can be quickly and easily obtained from
different mammalian genera through protocols that are well-suited for autologous
transplantations. Moreover, their multipotency makes them relevant to evaluate
therapeutic application in a wide variety of tissue injury models. This study
paves the way for the development of new fundamental and clinical studies based
on OE-MSCs transplantation and suggests their interest in veterinary medicine.
PMID- 29343272
TI - Biotechnologies that empower transgender persons to self-actualize as
individuals, partners, spouses, and parents are defining new ways to conceive a
child: psychological considerations and ethical issues.
AB - Today, thanks to biomedical technologies advances, some persons with fertility
issues can conceive. Transgender persons benefit also from these advances and can
not only actualize their self-identified sexual identities but also experience
parenthood. Based on clinical multidisciplinary seminars that gathered child
psychiatrists and psychoanalysts interested in the fields of assisted
reproduction technology (ART) and gender dysphoria, philosophers interested in
bioethics, biologists interested in ART, and endocrinologists interested in
pubertal suppression, we explore how new biotechnical advances, whether in gender
transition or procreation, could create new ways to conceive a child possible.
After reviewing the various medical/surgical techniques for physical gender
transition and the current ART options, we discuss how these new ways for persons
to self-actualize and to experience parenthood can not only improve the condition
of transgender persons (and the human condition as a whole through greater
equity) but also introduce some elements of change in the habitual patterns of
thinking especially in France. Finally, we discuss the ethical issues that
accompany the arrival of these children and provide creative solutions to help
society handle, accept, and support the advances made in this area.
PMID- 29343273
TI - INPP4B promotes cell survival via SGK3 activation in NPM1-mutated leukemia.
AB - BACKGROUND: Acute myeloid leukemia (AML) with mutated nucleophosmin (NPM1) has
been recognized as a distinct leukemia entity in the 2016 World Health
Organization (WHO) classification. The genetic events underlying oncogenesis in
NPM1-mutated AML that is characterized by a normal karyotype remain unclear.
Inositol polyphosphate 4-phosphatase type II (INPP4B), a new factor in the
phosphoinositide-3 kinase (PI3K) pathway-associated cancers, has been recently
found a clinically relevant role in AML. However, little is known about the
specific mechanistic function of INPP4B in NPM1-mutated AML. METHODS: The INPP4B
expression levels in NPM1-mutated AML primary blasts and AML OCI-AML3 cell lines
were determined by qRT-PCR and western blotting. The effect of INPP4B knockdown
on OCI-AML3 leukemia cell proliferation was evaluated, using the Cell Counting
Kit-8 and colony formation assay. After INPP4B overexpression or knockdown, the
activation of serum and glucocorticoid-regulated kinase 3 (SGK3) and AKT was
assessed. The effects of PI3K signaling pathway inhibitors on the levels of p
SGK3 in OCI-AML3 cells were tested. The mass of PI (3,4) P2 and PI (3) P was
analyzed by ELISA upon INPP4B overexpression. Knockdown of SGK3 by RNA
interference and a rescue assay were performed to confirm the critical role of
SGK3 in INPP4B-mediated cell survival. In addition, the molecular mechanism
underlying INPP4B expression in NPM1-mutated leukemia cells was explored.
Finally, Kaplan-Meier survival analysis was conducted on the NPM1-mutated AML
cohort stratified into quartiles for INPP4B expression in The Cancer Genome Atlas
(TCGA) dataset. RESULTS: High expression of INPP4B was observed in NPM1-mutated
AML. Knockdown of INPP4B repressed cell proliferation in OCI-AML3 cells, whereas
recovered INPP4B rescued this inhibitory effect in vitro. Mechanically, INPP4B
enhanced phosphorylated SGK3 (p-SGK3) status, but did not affect AKT activation.
SGK3 was required for INPP4B-induced cell proliferation in OCI-AML3 cells. High
levels of INPP4B were at least partially caused by the NPM1 mutant via ERK/Ets-1
signaling. Finally, high expression of INPP4B showed a trend towards lower
overall survival and event-free survival in NPM1-mutated AML patients.
CONCLUSIONS: Our results indicate that INPP4B promotes leukemia cell survival via
SGK3 activation, and INPP4B might be a potential target in the treatment of NPM1
mutated AML.
PMID- 29343274
TI - Coexistent sickle-cell anemia and autoimmune disease in eight children: pitfalls
and challenges.
AB - BACKGROUND: Patients with sickle cell disease (SCD) present a defective
activation of the alternate complement pathway that increases the risk of
infection and is thought to predispose to autoimmune disease (AID). However,
coexisting AID and SCD is rarely reported, suggesting possible underdiagnosis due
to an overlapping of the symptoms. STUDY DESIGN: Among 603 patients with SCD
followed between 1999 and June 2016, we retrospectively searched for patients
with coexisting SCD and AID. RESULTS: We identified 8 patients aged from 7 to 17
years diagnosed with AID; juvenile idiopathic arthritis (n = 3), systemic lupus
erythematosus (n = 2), Sjogren's syndrome (n = 1) and autoimmune hepatitis (n =
2). The diagnosis of AID was often delayed due to similarities of the symptoms
with those of SCD. Patients treated with steroids experienced multiple vaso
occlusive crises and received prophylactic chronic blood transfusions when it was
possible. Tolerance to other immunosuppressive and biological treatments, such as
anti-TNF agents, was good. A remission of AID was achieved in 4 patients, without
worsening the course of the SCD. One patient underwent a geno-identical
hematopoietic stem cell transplantation that cured both diseases. Another one
underwent a successful liver transplantation. CONCLUSION: Coexistence of AID and
SCD generates diagnostic and therapeutic challenges. Early diagnosis of AID is
important to define the best treatment, which may include targeted biological
therapy.
PMID- 29343275
TI - Early Babesia canis transmission in dogs within 24 h and 8 h of infestation with
infected pre-activated male Dermacentor reticulatus ticks.
AB - BACKGROUND: This study was designed to assess the ability of fed male Dermacentor
reticulatus ticks to transmit Babesia canis to dogs after being detached from
previous canine or ovine hosts. METHODS: The study was an exploratory, parallel
group design conducted in two trials. All the animals were sero-negative for
babesiosis prior to enrolment. In a first trial, donor dogs and donor sheep were
infested with Babesia canis infected male and uninfected female ticks for 72 h.
The ticks were detached and the second group of host dogs were infested for 24 h
before tick removal. In a second trial, the experiment was repeated but the donor
animals were infested for 88 h and the second group of host dogs were infested
for 8 h prior to tick removal. After infestation, the dogs were maintained under
clinical surveillance and blood samples were collected for blood smear, IFA and
PCR analysis. A dog was considered infected if any of these tests were positive.
RESULTS: All of the dogs (6 out of 6) were infected after being exposed to pre
activated male ticks for 24 h. Half of the dogs were infected after being exposed
to pre-activated ticks for 8 h: 1 out of 3 dogs infested with ticks removed from
sheep and 2 out of 3 dogs infested with ticks removed from dog. All the infected
dogs were positive to blood smear, IFA and PCR. Three of these dogs exhibited
elevated body temperature (> 39.4 degrees C). CONCLUSIONS: This study
demonstrates the ability of male D. reticulatus to transmit B. canis to dogs. The
study also illustrates for the first time that, regardless of the first host on
which ticks may attach and start feeding, Babesia canis can be transmitted to
dogs within 8 h of infestation. Since no minimal transmission time can be
established for all possible natural situations, a strategy of prevention based
on anti-attachment or repellency is recommended.
PMID- 29343277
TI - First molecular detection and genetic characterization of Coxiella burnetii in
Zambian dogs and rodents.
AB - Coxiella burnetii, the causative agent of Q fever, is a zoonotic pathogen
associated with sylvatic or domestic transmission cycles, with rodents being
suspected to link the two transmission cycles. Infection and subsequent disease
in humans has historically been associated with contact with infected livestock,
especially sheep. However, recently there have been reports of Q fever outbreaks
associated with contact with infected rodents and dogs. Studies exploring the
potential role of these animal hosts in the epidemiology of Q fever in many
developing countries in Africa are very limited. This study aimed to determine
the potential role of rodents and dogs in the epidemiological cycle of C.
burnetti in Zambia. Using pathogen-specific polymerase chain reaction assays
targeting the 16S rRNA gene, C. burnetii was detected for the first time in 45%
of rodents (9/20), in one shrew and in 10% of domestic dogs (15/150) screened in
Zambia. Phylogenetic characterization of six samples based on the isocitrate
synthase gene revealed that the strains were similar to a group of isolates from
chronic human Q fever patients, goats and rodents reported in multiple
continents. Considering the close proximity of domestic dogs and rodents to
humans, especially in resource-limited communities, the presence of C. burnetii
in these animals could be of significant public health importance. It is thus
important to determine the burden of Q fever in humans in such resource-limited
communities where there is close contact between humans, rodents and dogs.
PMID- 29343276
TI - The antihyperlipidemic effects of fullerenol nanoparticles via adjusting the gut
microbiota in vivo.
AB - BACKGROUND: Nanoparticles (NPs) administered orally will meet the gut microbiota,
but their impacts on microbiota homeostasis and the consequent physiological
relevance remain largely unknown. Here, we describe the modulatory effects and
the consequent pharmacological outputs of two orally administered fullerenols NPs
(Fol1 C60(OH)7(O)8 and Fol113 C60(OH)11(O)6) on gut microbiota. RESULTS:
Administration of Fol1 and Fol113 NPs for 4 weeks largely shifted the overall
structure of gut microbiota in mice. The bacteria belonging to putative short
chain fatty acids (SCFAs)-producing genera were markedly increased by both NPs,
especially Fol1. Dynamic analysis showed that major SCFAs-producers and key
butyrate-producing gene were significantly enriched after treatment for 7-28
days. The fecal contents of SCFAs were consequently increased, which was
accompanied by significant decreases of triglycerides and total cholesterol
levels in the blood and liver, with Fol1 superior to Fol113. Under cultivation in
vitro, fullerenols NPs can be degraded by gut flora and exhibited a similar
capacity of inulin to promote SCFA-producing genera. The differential effects of
Fol1 and Fol113 NPs on the microbiome may be attributable to their subtly varied
surface structures. CONCLUSIONS: The two fullerenol NPs remarkably modulate the
gut microbiota and selectively enrich SCFA-producing bacteria, which may be an
important reason for their anti-hyperlipidemic effect in mice.
PMID- 29343278
TI - Lipoblastoma: a clinicopathologic review of 23 cases from a major tertiary care
center plus detailed review of literature.
AB - OBJECTIVE: Lipoblastoma is a rare neoplasm that occurs mostly in infants and
children. Although benign, it has a tendency for local recurrence. RESULTS:
Clinical and pathological features of 23 cases of lipoblastoma described.
Patients' age ranged from 8 months to 18 years with mean and median age 4.1 and
2.5 years, respectively. Male:female ratio was 2.8:1. Most common sites were
lower extremities (9 cases), followed by abdominal cavity and retroperitoneum (4
cases), and scrotum/groin (3 cases). Grossly, 22 tumors were well circumscribed
and multi nodular. All cases showed lobules composed of adipocytes and lipoblasts
with intervening fibrous septa and fine vascular network. Myxoid change, capsule
formation and septation were seen in all cases. Zonation was seen in 2 cases.
Follow-up was available in 14 out of 23 patients. Of these, 13 were alive and
free of disease with no evidence of any recurrent lesion. One patient with a
mediastinal infiltrating lipoblastoma experienced 4 recurrences. Lipoblastoma is
a benign adipocytic neoplasm of infants and young children. Correlation of
clinical and histological features helps in reaching a correct diagnosis. Owing
to a high recurrence rate following incomplete resection, a complete resection is
essential. Prognosis is excellent after complete resection.
PMID- 29343279
TI - Spatial distribution and habitat characterization of mosquito species during the
dry season along the Mara River and its tributaries, in Kenya and Tanzania.
AB - BACKGROUND: Vector-borne diseases are increasingly becoming a major health
problem among communities living along the major rivers of Africa. Although
larger water bodies such as lakes and dams have been extensively researched,
rivers and their tributaries have largely been ignored. This study sought to
establish the spatial distribution of mosquito species during the dry season and
further characterize their habitats along the Mara River and its tributaries.
METHODS: In this cross-sectional survey, mosquito larvae were sampled along the
Mara River, its two perennial tributaries (Amala and Nyangores), drying streams,
and adjacent aquatic habitats (e.g. swamps, puddles that receive direct sunlight
[open sunlit puddles], rock pools, hippo and livestock hoof prints, and vegetated
pools). Each habitat was dipped 20 times using a standard dipper. Distance
between breeding sites and human habitation was determined using global
positioning system coordinates. The collected mosquito larvae were identified
using standard taxonomic keys. Water physico-chemical parameters were measured in
situ using a multiparameter meter. Mean mosquito larvae per habitat type were
compared using analysis of variance and chi-square tests, while the relationship
between mosquito larvae and physico-chemical parameters was evaluated using a
generalized linear mixed model. The Cox-Stuart test was used to detect trends of
mosquito larvae distribution. The test allowed for verification of monotonic
tendency (rejection of null hypothesis of trend absence) and its variability.
RESULTS: A total of 4001 mosquito larvae were collected, of which 2712 (67.8%)
were collected from river/stream edge habitats and 1289 (32.2%) were sampled from
aquatic habitats located in the terrestrial ecosystem about 50 m away from the
main river/streams. Anopheles gambiae s.s, An. arabiensis, and An. funestus
group, the three most potent vectors of malaria in Sub-Saharan Africa, together
with other anopheline mosquitoes, were the most dominant mosquito species
(70.3%), followed by Culex quinquefasciatus and Cx. pipiens complex combined
(29.5%). Drying streams accounted for the highest number of larvae captured
compared to the other habitat types. A stronger relationship between mosquito
larvae abundance and dissolved oxygen (Z = 7.37, P <= 0.001), temperature (Z =
7.65, P <= 0.001), turbidity (Z = -5.25, P <= 0.001), and distance to the nearest
human habitation (Z = 4.57, P <= 0.001), was observed. CONCLUSIONS: Presence of
malaria and non-malaria mosquito larvae within the Mara River basin calls for
immediate action to curtail the insurgence of vector-borne diseases within the
basin. A vector control program should be conducted during the dry period,
targeting drying streams shown to produce the highest number of larval
mosquitoes.
PMID- 29343280
TI - Pregabalin versus placebo in targeting pro-nociceptive mechanisms to prevent
chronic pain after whiplash injury in at-risk individuals - a feasibility study
for a randomised controlled trial.
AB - BACKGROUND: Whiplash-associated disorders (WAD) are an enormous and costly burden
to Australian society. Up to 50% of people who experience a whiplash injury will
never fully recover. Whiplash is resistant to treatment and no early management
approach has yet been shown to prevent chronic pain. The early presence of
central sensitization is associated with poor recovery. Pregabalin's effects on
central sensitization indicate the potential to prevent or modulate these
processes after whiplash injury and to improve health outcomes, but this has not
been investigated. This paper describes the protocol for a feasibility study for
a randomised controlled trial of pregabalin plus evidence-based advice compared
to placebo plus evidence-based advice for individuals with acute whiplash injury
who are at risk of poor recovery. METHODS: This double blind, placebo-controlled
randomised feasibility study will examine the feasibility and potential
effectiveness of pregabalin and evidence-based advice (intervention) compared to
placebo and evidence-based advice (control) for individuals with acute whiplash
injury at risk of poor recovery. Thirty participants (15 per group) aged 18-65
years with Grade II WAD, within 48 hours of injury and currently experiencing at
least moderate pain (NRS: >= 5/10) will be recruited from Emergency Departments
of public hospitals in Queensland, Australia. Pregabalin will be commenced at 75
mg bd and titrated up to 300 mg bd as tolerated for 4 weeks followed by 1 week of
weaning. RESULTS: The feasibility of trial procedures will be tested, as well as
the potential effect of the intervention on the outcomes. The primary outcome of
neck pain intensity at 3 months from randomisation will be compared between the
treatment groups using standard analysis of variance techniques. DISCUSSION:
Feasibility and potential effectiveness data will inform an appropriately powered
full trial, which if successful, will provide an effective and cost-effective
intervention for a costly and treatment resistant condition. It will also have
implications for the early management of other traumatic conditions beyond
whiplash. TRIAL REGISTRATION: Clinical Trials Primary Registry: Australian and
New Zealand Clinical Trials Registry. CLINICAL TRIAL REGISTRATION NUMBER:
ACTRN12617000059369 . Date of Registration: 11/01/2017. Primary Trial Sponsor:
The University of Queensland, Brisbane QLD 4072 Australia.
PMID- 29343281
TI - P-MAPA immunotherapy potentiates the effect of cisplatin on serous ovarian
carcinoma through targeting TLR4 signaling.
AB - BACKGROUND: Toll-like receptors (TLRs) are transmembrane proteins expressed on
the surface of ovarian cancer (OC) and immune cells. Identifying the specific
roles of the TLR-mediated signaling pathways in OC cells is important to guide
new treatments. Because immunotherapies have emerged as the adjuvant treatment
for patients with OC, we investigated the effect of a promising immunotherapeutic
strategy based on protein aggregate magnesium-ammonium phospholinoleate
palmitoleate anhydride (P-MAPA) combined with cisplatin (CIS) on the TLR2 and
TLR4 signaling pathways via myeloid differentiation factor 88 (MyD88) and TLR
associated activator of interferon (TRIF) in an in vivo model of OC. METHODS:
Tumors were chemically induced by a single injection of 100 MUg of 7,12
dimethylbenz(a)anthracene (DMBA) directly under the left ovarian bursa in Fischer
344 rats. After the rats developed serous papillary OC, they were given P-MAPA,
CIS or the combination P-MAPA+CIS as therapies. To understand the effects of the
treatments, we assessed the tumor size, histopathology, and the TLR2- and TLR4
mediated inflammatory responses. RESULTS: Although CIS therapy was more effective
than P-MAPA in reducing the tumor size, P-MAPA immunotherapy significantly
increased the expressions of TLR2 and TLR4. More importantly, the combination of
P-MAPA with CIS showed a greater survival rate compared to CIS alone, and
exhibited a significant reduction in tumor volume compared to P-MAPA alone. The
combination therapy also promoted the increase in the levels of the following OC
related proteins: TLR4, MyD88, TRIF, inhibitor of phosphorylated NF-kB alpha (p
IkBalpha), and nuclear factor kappa B (NF-kB p65) in both cytoplasmic and nuclear
sites. While P-MAPA had no apparent effect on tumor necrosis factor alpha (TNF
alpha) and interleukin (IL)-6, it seems to increase interferon-gamma (IFN-gamma),
which may induce the Thelper (Th1)-mediated immune response. CONCLUSION:
Collectively, our results suggest that P-MAPA immunotherapy combined with
cisplatin could be considered an important therapeutic strategy against OC cells
based on signaling pathways activated by TLR4.
PMID- 29343282
TI - Investigation of perioperative safety and clinical results of one-stage bilateral
total knee arthroplasty in selected low-risk patients.
AB - BACKGROUND: An increased perioperative complication rate has been a concern with
one-stage bilateral total knee arthroplasty (TKA). The purpose of this study was
to retrospectively investigate the perioperative safety and clinical results of
one-stage bilateral TKA in selected low-risk patients. METHODS: Sixty-seven
patients who received one-stage bilateral TKAs for osteoarthritis who were
American Society of Anesthesiology (ASA) class 1 or 2 were included in this
study. Perioperative complications, blood loss, transfusion rate, blood
laboratory results, and clinical results were evaluated up to 1 year after
surgery. RESULTS: No major complications (deep infection, pulmonary embolism,
cerebrovascular accident, myocardial infarction, death, or removal or revision of
the implants) were observed. The average total blood loss was 1139.5 ml. The
transfusion rate was 95.5%. Postoperative hemoglobin level and C-reactive protein
level gradually improved up to postoperative day 21 (P < 0.01). Bilateral knee
extension knee angles and clinical scores improved postoperatively as compared
with preoperative values (P < 0.01). CONCLUSIONS: Although total blood loss and
transfusion rate can be high, this preliminary case series suggested that the one
stage bilateral TKA in ASA class 1 or 2 patients can have high perioperative
safety levels, and good clinical results can be obtained up to 1 year after
surgery. If low-risk patients are selected for bilateral TKA, a one-stage
procedure can be beneficial for patients, with a minimal increase in the risk of
complications.
PMID- 29343283
TI - The Classroom Communication Resource (CCR) intervention to change peer's
attitudes towards children who stutter (CWS): study protocol for a randomised
controlled trial.
AB - BACKGROUND: Children who stutter (CWS) are at a high-risk of being teased and
bullied in primary school because of negative peer attitudes and perceptions
towards stuttering. There is little evidence to determine if classroom-based
interventions are effective in changing peer attitudes towards stuttering. The
primary objective is to determine the effect of the Classroom Communication
Resource (CCR) intervention versus usual practice, measured using the Stuttering
Resource Outcomes Measure (SROM) 6-months post-intervention among grade 7
students. The secondary objective is to investigate attitude changes towards
stuttering among grade participants on the SROM subscales. METHODS: A cluster
randomised controlled trial (RCT) will be conducted with schools as the unit of
randomization. Schools will be stratified into quintile groups, and then
randomized to receive the CCR intervention or usual practice. Quintile
stratification will be conducted in accordance to the Western Cape Department of
Education classification of schools according to geographical location, fee per
school and allocation of resources and funding. Participants will include primary
schools in the lower (second and third) and higher (fourth and fifth) quintiles
and children aged 11 years or older in grade 7 will be included. The study will
consist of the CCR intervention program or usual practice as a no-CCR control.
The CCR is a classroom-based, teacher led intervention tool including a story,
role-play and discussion. The grade 7 teachers allocated to the CCR intervention,
will be trained and will administer the intervention. The analysis will follow
intention-to-treat (ITT) principle and generalized estimating equations (GEE) to
compare groups on the global SROM and its subscales to account for possible
clustering within schools. The subgroup hypothesis will be tested by adding an
interaction term of quintile group x intervention. DISCUSSION: This study is
designed to assess whether the CCR intervention versus usual practice in schools
will lead to positive shift in attitudes about stuttering at 6-months post
intervention among grade 7 participants. TRIAL REGISTRATION: The trial number is
NCT03111524 . It was registered with clinical trials.gov Protocol registration
and results system (PRS) retrospectively on 9 March 2017.
PMID- 29343284
TI - Extensive ARMC5 genetic variance in primary bilateral macronodular adrenal
hyperplasia that started with exophthalmos: a case report.
AB - BACKGROUND: Primary bilateral macronodular adrenal hyperplasia is a rare cause of
Cushing's syndrome characterized by the presence of bilateral secretory adrenal
nodules. Recent studies have shown that primary bilateral macronodular adrenal
hyperplasia is caused by combined germline and somatic mutations of the ARMC5
gene. Exophthalmos is an underappreciated sign of Cushing's syndrome. CASE
PRESENTATION: A 52-year-old Chinese woman with progressively worsening bilateral
proptosis presented to our hospital. Subsequently she was diagnosed as having
primary bilateral macronodular adrenal hyperplasia and underwent bilateral
laparoscopic adrenalectomy. Genomic deoxyribonucleic acid was isolated from
lymphocytes as well as seven different adrenal nodules and the ARMC5 sequence was
determined by Sanger sequencing. We identified one heterozygous ARMC5 germline
mutation c.682C>T (p. Gln228*) and five heterozygous somatic mutations
(c.310delG, c.347_357del11, c.267delC, c.283_289del7, and c.205-322del118) in
five different adrenal nodules. All mutations are novel and were not found in any
of the available online databases. To test whether the ARMC5 mutation induced
messenger ribonucleic acid decay, real-time reverse transcriptase polymerase
chain reaction was performed on patient and control adrenal tissue. We found that
the adrenal cortex of our patient showed a low ARMC5 messenger ribonucleic acid
expression compared with normal adrenal cortex, possibly as a result of nonsense
mediated messenger ribonucleic acid decay CONCLUSIONS: We demonstrated extensive
genetic diversity of ARMC5 in a patient with primary bilateral macronodular
adrenal hyperplasia that started with exophthalmos, which contributes to further
understanding of the pathogenesis of this disease. Early recognition of atypical
symptoms and screening for ARMC5 mutation in patients with primary bilateral
macronodular adrenal hyperplasia has important clinical implications for the
diagnosis and genetic counseling.
PMID- 29343285
TI - Cyberbullying a modern form of bullying: let's talk about this health and social
problem.
AB - Cyberbullying or electronic aggression has already been designated as a serious
public health threat. Cyberbullying should also be considered as a cause for new
onset psychological symptoms, somatic symptoms of unclear etiology or a drop in
academic performance. Pediatricians should be trained to play a major role in
caring for and supporting the social and developmental well-being of children.
PMID- 29343287
TI - Percutaneous kyphoplasty for the treatment of very severe osteoporotic vertebral
compression fractures with spinal canal compromise.
AB - BACKGROUND: Very severe osteoporotic vertebral compression fractures (vsOVCFs)
are osteoporotic vertebral compression fractures with vertebral body collapse to
less than one third of their original height. Few data are available about the
use of percutaneous kyphoplasty (PKP) in treating vsOVCFs with spinal canal
compromise. The aim of this study was to evaluate the safety and efficacy of
percutaneous kyphoplasty (PKP) for the treatment of vsOVCFs with spinal canal
compromise. METHODS: Thirty-five patients who suffered vsOVCFs with spinal canal
compromise but without neurological deficits were treated by PKP between January
2009 and October 2014. The vertebral height, local kyphotic angle (LKA), visual
analogue scale (VAS) and Oswestry Disability Index (ODI) values were assessed
before the operation, 1 day after the operation and at the final follow-up.
RESULTS: Significant improvements on the VAS and ODI were noted 1 day post
operatively (p < 0.01), and these results were preserved at the final follow-up.
The vertebral height was restored and the LKA was improved after surgery (p <
0.01). No neurological deterioration was found. Five of 35 vertebrae (14.3%) of
cement leakages were all asymptomatic. Four new OVCFs in three patients were
identified. CONCLUSION: PKP is a safe and effective procedure for the treatment
of vsOVCFs with spinal canal compromise, achieving significant vertebral height
restoration and kyphotic angle reduction and leading to a significant pain relief
and improvement in function.
PMID- 29343286
TI - Diagnosis and management of transthyretin familial amyloid polyneuropathy in
Japan: red-flag symptom clusters and treatment algorithm.
AB - Hereditary ATTR (ATTRm) amyloidosis (also called transthyretin-type familial
amyloid polyneuropathy [ATTR-FAP]) is an autosomal-dominant, adult-onset, rare
systemic disorder predominantly characterized by irreversible, progressive, and
persistent peripheral nerve damage. TTR gene mutations (e.g. replacement of
valine with methionine at position 30 [Val30Met (p.Val50Met)]) lead to
destabilization and dissociation of TTR tetramers into variant TTR monomers,
which form amyloid fibrils that deposit in peripheral nerves and various organs,
giving rise to peripheral and autonomic neuropathy and several non-disease
specific symptoms.Phenotypic and genetic variability and non-disease-specific
symptoms often delay diagnosis and lead to misdiagnosis. Red-flag symptom
clusters simplify diagnosis globally. However, in Japan, types of TTR variants,
age of onset, penetrance, and clinical symptoms of Val30Met are more varied than
in other countries. Hence, development of a Japan-specific red-flag symptom
cluster is warranted. Presence of progressive peripheral sensory-motor
polyneuropathy and >=1 red-flag sign/symptom (e.g. family history, autonomic
dysfunction, cardiac involvement, carpal tunnel syndrome, gastrointestinal
disturbances, unexplained weight loss, and immunotherapy resistance) suggests
ATTR-FAP. Outside of Japan, pharmacotherapeutic options are first-line therapy.
However, because of positive outcomes (better life expectancy and higher survival
rates) with living donor transplant in Japan, liver transplantation remains first
line treatment, necessitating a Japan-specific treatment algorithm.Herein, we
present a consolidated review of the ATTR-FAP Val30Met landscape in Japan and
summarize findings from a medical advisory board meeting held in Tokyo on 18th
August 2016, at which a Japan-specific ATTR-FAP red-flag symptom cluster and
treatment algorithm was developed. Beside liver transplantation, a TTR
stabilizing agent (e.g. tafamidis) is a treatment option. Early diagnosis and
timely treatment using the Japan-specific red-flag symptom cluster and treatment
algorithm might help guide clinicians regarding apt and judicious use of
available treatment modalities.
PMID- 29343288
TI - Changes in the secretome of tri-dimensional spheroid-cultured human mesenchymal
stem cells in vitro by interleukin-1 priming.
AB - BACKGROUND: Mesenchymal stem cells (MSCs) are one of the most promising
candidates for the treatment of major neurological disorders. Desirable
therapeutic properties of MSCs include reparative and regenerative potential but,
despite their proven safety, the efficacy of MSCs remains controversial.
Therefore, it is essential to optimise culture protocols to enhance the
therapeutic potential of the MSC secretome. Here we aimed to: assess the increase
in secretion of cytokines that may induce repair, regeneration, or
immunomodulation when cultured in three dimensions; study the effect of
interleukin (IL)-1 priming on two- (2D) and three-dimensional (3D) cultures of
MSC; and evaluate the potential use of the modified secretome using microglial
MSC co-cultures. METHODS: We established a 3D spheroid culture of human MSCs, and
compared the secretome in 2D and 3D cultures under primed (IL-1) and unprimed
conditions. BV2 microglial cells were stimulated with lipopolysaccharide (LPS)
and treated with spheroid conditioned media (CM) or were co-cultured with whole
spheroids. Concentrations of secreted cytokines were determined by enzyme-linked
immunosorbent assay (ELISA). Protein arrays were used to further evaluate the
effect of IL-1 priming in 2D and 3D cultures. RESULTS: 3D culture of MSCs
significantly increased secretion of the IL-1 receptor antagonist (IL-1Ra),
vascular endothelial growth factor (VEGF), and granulocyte-colony stimulating
factor (G-CSF) compared with 2D culture, despite priming treatments with IL-1
being more effective in 2D than in 3D. The addition of CM of 3D-MSCs reduced LPS
induced tumour necrosis factor (TNF)-alpha secretion from BV2 cells, while the 3D
spheroid co-cultured with the BV2 cells induced an increase in IL-6, but had no
effect on TNF-alpha release. Protein arrays indicated that priming treatments
trigger a more potent immune profile which is necessary to orchestrate an
effective tissue repair. This effect was lost in 3D, partly because of the
overexpression of IL-6. CONCLUSIONS: Increased secretion of anti-inflammatory
markers occurs when MSCs are cultured in 3D, but this specific secretome did not
translate into anti-inflammatory effects on LPS-treated BV2 cells in co-culture.
These data highlight the importance of optimising priming treatments and culture
conditions to maximise the therapeutic potential of MSC spheroids.
PMID- 29343289
TI - Differentiated thyroid carcinoma presentation may be more aggressive in children
and adolescents than in young adults.
AB - BACKGROUND: The available studies concerning the influence of age on the
phenotypical expression of differentiated thyroid carcinoma (DTC) have hitherto
compared DTC presentation either between pre-pubertal and pubertal children or
between pediatric patients and aged adults; aim of this study was to ascertain
for the first time whether presentation of DTC may significantly vary according
to age, even within a peculiar study population covering only young patients aged
less than 30 years. METHODS: The main clinical, biochemical and pathologic data
at DTC diagnosis were retrospectively recorded in 2 selected cohorts including,
respectively, 18 children and adolescents aged less than 18 years (Group A) or 45
young adults aged between 20 and 29.8 years (Group B). RESULTS: The statistical
distribution of DTC cases in the different age ranges was found to progressively
increase with increasing age; furthermore, the patients of Group A exhibited at
diagnosis a more severe clinical involvement and a higher rate of extra-regional
metastases; finally, also the association with both autoimmune thyroid diseases
(AITDs) and a biochemical hypothyroid pattern was more common in Group A
patients. CONCLUSIONS: In a study population younger than 30 years: a) the risk
of developing DTC increases with age, achieving its zenith during the 3rd decade
of life; b) clinical presentation is more severe in children and adolescents
younger than 18 years than in the patients aged between 20 and 30; c) in the
cohort of children and adolescents DTC is more often associated with AITDs, which
might play some role in conditioning the more aggressive phenotypical
presentation of DTC in this patient group.
PMID- 29343291
TI - Trends in the performance of quality indicators for diabetes care in the
community and in diabetes-related health status: an Israeli ecological study.
AB - BACKGROUND: Israel is one of the few countries that have a national program for
quality assessment of community healthcare. We aimed to evaluate whether improved
performance in diabetes care was associated with improved health of diabetic
patients on a national level. METHODS: We conducted a nationwide ecological study
estimating improvements in diabetes-related quality indicators and health
outcomes. We estimated both correlations between composite measures of diabetes
related quality indicators and selected outcomes, and assessed through a
joinpoint analysis whether trends in selected outcomes changed 4 years after the
inception of the national program. RESULTS: Between 2002 and 2010, the prevalence
of diabetes in Israeli adults increased from 4.8% to 7.4%. During these years, an
improvement was noticed in most quality indicators (from 53% to 75% for the
composite score). Declines were noted in rates of blindness, diabetes-related end
stage kidney disease, lower limbs amputations and diabetes-related mortality.
Significant accelerations in decline were noted for amputations in men and
diabetes-related mortality in both Arab men and women 4 years after the inception
of the national program. CONCLUSION: This study suggests that Israel's national
program for quality indicators in diabetes care in the community has probably had
a significant impact on the health status of the whole population and may have
contributed to narrowing gaps in life expectancy between Israeli Jews and Arabs.
Future studies based on individual-level data are needed to confirm these
results.
PMID- 29343290
TI - FineMAV: prioritizing candidate genetic variants driving local adaptations in
human populations.
AB - We present a new method, Fine-Mapping of Adaptive Variation (FineMAV), which
combines population differentiation, derived allele frequency, and molecular
functionality to prioritize positively selected candidate variants for functional
follow-up. We calibrate and test FineMAV using eight experimentally validated
"gold standard" positively selected variants and simulations. FineMAV has good
sensitivity and a low false discovery rate. Applying FineMAV to the 1000 Genomes
Project Phase 3 SNP dataset, we report many novel selected variants, including
ones in TGM3 and PRSS53 associated with hair phenotypes that we validate using
available independent data. FineMAV is widely applicable to sequence data from
both human and other species.
PMID- 29343292
TI - Global trends in the awareness of sepsis: insights from search engine data
between 2012 and 2017.
AB - BACKGROUND: Sepsis is an established global health priority with high mortality
that can be curtailed through early recognition and intervention; as such,
efforts to raise awareness are potentially impactful and increasingly common. We
sought to characterize trends in the awareness of sepsis by examining temporal,
geographic, and other changes in search engine utilization for sepsis information
seeking online. METHODS: Using time series analyses and mixed descriptive
methods, we retrospectively analyzed publicly available global usage data
reported by Google Trends (Google, Palo Alto, CA, USA) concerning web searches
for the topic of sepsis between 24 June 2012 and 24 June 2017. Google Trends
reports aggregated and de-identified usage data for its search products,
including interest over time, interest by region, and details concerning the
popularity of related queries where applicable. Outlying epochs of search
activity were identified using autoregressive integrated moving average modeling
with transfer functions. We then identified awareness campaigns and news media
coverage that correlated with epochs of significantly heightened search activity.
RESULTS: A second-order autoregressive model with transfer functions was
specified following preliminary outlier analysis. Nineteen significant outlying
epochs above the modeled baseline were identified in the final analysis that
correlated with 14 awareness and news media events. Our model demonstrated that
the baseline level of search activity increased in a nonlinear fashion. A
recurrent cyclic increase in search volume beginning in 2012 was observed that
correlates with World Sepsis Day. Numerous other awareness and media events were
correlated with outlying epochs. The average worldwide search volume for sepsis
was less than that of influenza, myocardial infarction, and stroke. CONCLUSIONS:
Analyzing aggregate search engine utilization data has promise as a mechanism to
measure the impact of awareness efforts. Heightened information-seeking about
sepsis occurs in close proximity to awareness events and relevant news media
coverage. Future work should focus on validating this approach in other contexts
and comparing its results to traditional methods of awareness campaign
evaluation.
PMID- 29343293
TI - Identification of preoperative prediction factors of tumor subtypes for patients
with solitary ground-glass opacity pulmonary nodules.
AB - BACKGROUND: Recent wide spread use of low-dose helical computed tomography for
the screening of lung cancer have led to an increase in the detection rate of
very faint and smaller lesions known as ground-glass opacity nodules. The purpose
of this study was to investigate the clinical factors of lung cancer patients
with solitary ground-glass opacity pulmonary nodules on computed tomography.
METHODS: A total of 423 resected solitary ground-glass opacity nodules were
retrospectively evaluated. We analyzed the clinical, imaging and pathological
data and investigated the clinical differences in patient with adenocarcinoma in
situ / minimally invasive adenocarcinoma and those with invasive adenocarcinoma.
RESULTS: Three hundred and ninety-three adenocarcinomas (92.9%) and 30 benign
nodules were diagnosed. Age, the history of family cancer, serum carcinoembryonic
antigen level, tumor size, ground-glass opacity types, and bubble-like sign in
chest CT differed significantly between adenocarcinoma in situ / minimally
invasive adenocarcinoma and invasive adenocarcinoma (p:0.008, 0.046, 0.000,
0.000, 0.000 and 0.001). Receiver operating characteristic curves and univariate
analysis revealed that patients with more than 58.5 years, a serum
carcinoembryonic antigen level > 1.970 MUg/L, a tumor size> 13.50 mm, mixed
ground-glass opacity nodules and a bubble-like sign were more likely to be
diagnosed as invasive adenocarcinoma. The combination of five factors above had
an area under the curve of 0.91, with a sensitivity of 82% and a specificity of
87%. CONCLUSION: The five-factor combination helps us to distinguish
adenocarcinoma in situ / minimally invasive adenocarcinoma from invasive
adenocarcinoma and to perform appropriate surgery for solitory ground-glass
opacity nodules.
PMID- 29343294
TI - Effect of glycaemic control on complications following cardiac surgery:
literature review.
AB - INTRODUCTION: No uniform consensus in the UK or Europe exists, for glycaemic
management of patients with Diabetes or pre-diabetes undergoing cardiac surgery.
OBJECTIVE: [i] Determine the relationship between glycaemic control and cardiac
surgical outcomes; [ii] Compare current vs gold standard management of patients
with Diabetes or pre-diabetes undergoing cardiac surgery. METHODS: Searches of
MEDLINE, NHS Evidence and Web of Science databases were completed. Articles were
limited to those in English, German and French. No date limit was enforced.13,232
articles were identified on initial literature review, and 50 relevant papers
included in this review. RESULTS: No national standards for glycaemic control
prior to cardiac surgery were identified. Upto 30% of cardiac surgical patients
have undiagnosed Diabetes. Cardiac surgical patients without Diabetes with pre
operative hyperglycaemia have a 1 year mortality double that of patients with
normoglyacemia, and equivalent to patients already diagnosed with Diabetes. Pre-
and peri-operative hyperglycaemia is associated with worse outcomes. Evidence
regarding tight glycaemic control vs moderate glycaemic control is conflicting.
Tight control may be more effective in patients without Diabetes with pre-/peri
operative hyperglycaemia, and moderate control appears more effective in patients
with pre-existing Diabetes. Patients with well controlled Diabetes may achieve
comparable outcomes to patients without Diabetes with similar glycaemic control.
CONCLUSIONS: Pre / peri-operative hyperglycaemia is associated with worse
outcomes in both patients with, and without Diabetes undergoing CABG. This review
supports the pre-operative screening, and optimisation of glycaemic control in
patients undergoing cardiac surgery. Optimal glycaemic management remains unclear
and clear guidelines are needed.
PMID- 29343295
TI - Cytotoxic T lymphocytes from cattle sharing the same MHC class I haplotype and
immunized with live Theileria parva sporozoites differ in antigenic specificity.
AB - OBJECTIVES: The objective of this study was to assess whether cytotoxic T cells
(CTL) generated by the live vaccine, known as "ITM Muguga cocktail", which is
used for the cattle disease East Cost fever (ECF) in Sub-Saharan Africa, showed a
broad reactivity against many different strains of the causative parasite
Theileria parva. We also assessed whether immune responses were similar in cattle
expressing the same MHC class I haplotypes. RESULTS: The antigenic specificity of
CTL from MHC class I-matched cattle vaccinated with the Muguga cocktail were
different. Three cattle of MHC class I haplotype A18, one A18/A19 and two
haploidentical (A18v/A12) animals, showed differential recognition of autologous
cells infected with a panel of T. parva isolates. This could have implications in
the field where certain strains could break through the vaccine. Furthermore,
neither of the haploidentical cattle recognized the CTL epitope (Tp1214-224),
presented by the A18 haplotype, in contrast to the third animal, showing
differences in immunodominance in animals of the same haplotype A18. This
suggests that the CTL specificities following immunization with the Muguga
cocktail can vary even between haploidentical individuals and that some parasite
strains may break through immunity generated by the Muguga cocktail.
PMID- 29343296
TI - Quantitative method for analysis of six anticoagulant rodenticides in faeces,
applied in a case with repeated samples from a dog.
AB - BACKGROUND: Accidental poisoning with anticoagulant rodenticides is not uncommon
in dogs, but few reports of the elimination kinetics and half-lives in this
species have been published. Our objectives were to develop and validate a new
method for the quantification of anticoagulant rodenticides in canine blood and
faeces using reversed phase ultra-high performance liquid chromatography-tandem
mass spectrometry (UHPLC-MS/MS) and apply the method on a case of anticoagulant
rodenticide intoxication. RESULTS: Sample preparation was liquid-liquid
extraction. Six anticoagulant rodenticides were separated using a UPLC(r) BEH C18
column with a mobile phase consisting of 5 mM ammonium formate buffer pH 10.2 and
methanol. MS/MS detection was performed with positive electrospray ionization and
two multiple reaction monitoring transitions. The limits of quantification were
set at the levels of the lowest calibrator (1.5-2.7 ng/mL or ng/g). The method
was successfully applied to a case from a dog accidentally poisoned with
anticoagulant rodenticide. Coumatetralyl and brodifacoum concentrations were
determined from serial blood and faecal samples. A terminal half-life of at least
81 days for coumatetralyl in blood was estimated, which is longer than previous
reported in other species. A slow elimination of brodifacoum from the faeces was
found, with traces still detectable in the faeces at day 513. CONCLUSIONS: This
study offers a new method of detection and quantification of six frequently used
anticoagulant rodenticides in canine faeces. Such drugs might cause serious
health effects and it is important to be able to detect these drugs, to initiate
proper treatment. The very long elimination half-lives detected in our study is
important to be aware of in assessment of anticoagulant rodenticide burden to the
environment.
PMID- 29343297
TI - Pulmonary valve replacement after right ventricular outflow tract reconstruction
with homograft vs Contegra(r): a case control comparison of mortality and
morbidity.
AB - BACKGROUND: Repair of congenital heart defects involving the right ventricular
outflow tract may require the implantation of a right ventricle to pulmonary
artery conduit. This conduit is likely to be replaced during childhood. This
study compares the operative outcomes of the replacement procedure of Contegra(r)
and homografts in pulmonary position. METHODS: From 1999 to 2016, 82 children
underwent 87 right ventricle to pulmonary artery conduit replacements (60
Contegra(r) and 27 homografts). Demographics, operative and clinical data were
obtained through a retrospective review of the medical records. The two groups
were matched for comparison using propensity score matching. All the procedures
were performed by the same team of surgeons. RESULTS: No statistically
significant difference was observed between the two groups when considering the
operative data for anesthesia, surgery, cardiopulmonary bypass and aortic
clamping durations. A peroperative complication rate of 13.47% and 15.36% in
Contegra(r) and homograft replacement groups respectively (p value = 0.758) was
observed. There was no difference regarding the blood loss and fluid input. No
statistically significant difference was observed between the two groups for the
post-operative morbidity. We considered the Pediatric Risk of Mortality (PRISM)
score, the day of extubation, the day of withdrawal of inotropic drugs, the
length of the intensive care unit stay and the length of hospital stay. The
overall mortality is 2.3% but there is no statistically significant difference
between the two groups. CONCLUSION: Right ventricle to pulmonary artery conduit
replacement procedure can be achieved with a low surgical morbidity or mortality,
not influenced by the type of conduit that is replaced. Therefore, the choice
between homograft or Contegra(r) for right ventricle to pulmonary artery
reconstruction should not be influenced by the future surgical risk during the
replacement procedure. TRIAL REGISTRATION: NCT03048071 . Registered 9 February
2017 (retrospectively registered).
PMID- 29343298
TI - Circular RNAs: biogenesis, expression and their potential roles in reproduction.
AB - Unlike other non-coding RNAs (ncRNAs), circular RNA (circRNA) is generally
presented as a covalently linked circle lacking both a 5' cap and a 3' tail.
circRNAs were thought to be spliced intermediates, byproducts, or products of
abnormal RNA splicing events. However, the high-throughput sequencing technology
coupled with bioinformatics has recently uncovered thousands of endogenous
circRNAs in cells of many different species. These circRNAs show various
features, such as abundant expression, evolutionary conservation, cell- or tissue
specific expression, and a higher resistance to degradation caused by exonuclease
or ribonuclease (RNase), suggesting their potentially biological significance.
However, the function of these circRNAs, their mechanism of action, and the
regulation of their biogenesis and degradation remains largely unclear. The
current research and findings of circRNA in the context of reproduction will be
reviewed. Additionally, the perspectives of circRNAs in the field will be
discussed.
PMID- 29343299
TI - Atypical phenotypic aspects of autoimmune thyroid disorders in young patients
with Turner syndrome.
AB - : Aim of this commentary is to analyze the current views about the phenotypic
features of Hashimoto's thyroiditis (HT) and Graves' disease (GD) in Turner
syndrome (TS) girls, in terms of epidemiology, clinical and biochemical
presentation, long-term course and metamorphic autoimmunity evolution. In TS GD
course is not atypical, whereas HT course is characterized by both a mild
presenting picture and a severe long-term evolution of thyroid function tests.
Furthermore, TS girls seem to have an increased risk of switching over time from
HT to GD. On the light of these findings, it may be concluded that TS girls with
HT need a careful monitoring of thyroid status over time. CONCLUSIONS: 1) In
children the association with TS is able to condition a peculiar phenotypic
expression of HT in terms of epidemiology, presentation course and long-term
metamorphic autoimmunity; 2) by contrast, children with TS do not exhibit an
atypical clinical and biochemical course of GD, but only a significantly higher
prevalence of this disease.
PMID- 29343300
TI - Association between sickle cell and beta-thalassemia genes and hemoglobin
concentration and anemia in children and non-pregnant women in Sierra Leone:
ancillary analysis of data from Sierra Leone's 2013 National Micronutrient
Survey.
AB - OBJECTIVE: By measuring the associations between the presence of sickle cell and
beta-thalassemia genes, we assessed the extent to which these hemoglobinopathies
contribute to the high prevalence of anemia observed in preschool-aged children
and women of reproductive age in Sierra Leone. RESULTS: The prevalence of anemia
was statistically significantly higher in children with homozygous sickle cell
genes (HbSS) than in children with normal hemoglobin genes (HbAA or HbAC), but
there was no difference in anemia prevalence in those with heterozygous sickle
cell trait (HbAS or HbSC) compared with those with normal hemoglobin genes. In
women, there was no difference in anemia prevalence by sickle cell status. In
both children and women, there was no difference in the anemia prevalence for
individuals with or without the beta-thalassemia gene. For both sickle cell and
beta-thalassemia, there was no significant difference in hemoglobin
concentrations by sickle cell or beta-thalassemia status. Anemia prevalence was
higher in children and women with homozygous sickle cell (HbSS). However, as the
prevalence of HbSS children (5.4%) and women (1.6%) was quite small, it is
unlikely that these hemoglobinopathies substantially contributed to the high
anemia prevalence found in the 2013 national micronutrient survey.
PMID- 29343301
TI - Circulating PCSK9 levels and 2-hPG are positively correlated in metabolic
diseases in a Chinese Han population.
AB - BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9), which plays a
crucial role in lipoprotein metabolism, has been also regarded as an important
marker for atherosclerosis. Available evidence indicated that 2-h postchallenge
plasma glucose (2-hPG) could be another biomarker for atherosclerosis. However,
currently the association between circulating PCSK9 and 2-hPG remains unclear.
Here, we explored this potential link in a Chinese Han population. METHODS:
Totally, 600 Chinese Han subjects from Nanjing district, China, were enrolled for
the 75-g oral glucose tolerance test (OGTT), and they included normal glucose
tolerance (NGT, n = 200), impaired glucose regulation (IGR, n = 200), and type 2
diabetes (T2DM, n = 200). Anthropometric and biochemical determinations such as
serum lipid measurements were made. A sandwich ELISA assay was performed to
measure serum PCSK9 levels in all subjects. RESULTS: Serum PCSK9 concentrations
were higher in IGR group (77.63 +/- 28.14 ng/ml) and T2DM group (90.62 +/- 39.96
ng/ml) than in NGT group (65.33 +/- 32.68 ng/ml), and it was significantly higher
in T2DM group than in IGR group (p < 0.01). Serum PCSK9 levels positively
correlated with 2-hPG and LDL-C in all subgroups, but presented a positive
correlation with fasting blood glucose (FBG) only in T2DM group. Using multiple
regression model analysis, we also found that PCSK9 levels closely correlated
with 2-hPG in all tested groups. According to multinomial logistic regression
analysis, PCSK9 levels positively correlated with T2DM (OR = 1.017[1.010-1.025],
p < 0.001) even after adjustment for lipid levels. Moreover, in subjects with
normal FBG level, 2-hPG gradually and significantly increased across PCSK9
tertiles (6.68 +/- 2.01, 7.48 +/- 2.10 and 8.27 +/- 2.41 mmol/L, respectively, p
< 0.01); however, in subjects with normal 2-hPG levels, no such difference was
observed. CONCLUSIONS: PCSK9 levels increase as glucose metabolism deteriorated.
Serum PCSK9 levels positively correlated with 2-hPG in patients with metabolic
diseases.
PMID- 29343302
TI - Does previous abdominal surgery adversely affect perioperative and oncologic
outcomes of laparoscopic radical cystectomy?
AB - BACKGROUND: Laparoscopic radical cystectomy (LRC) has been shown to have less
estimated blood loss (EBL), transfusion rate, narcotic analgesic requirement,
earlier return of bowel function, and shorter hospital stay. The aim of this
study was to investigate the feasibility, peri-operative and oncologic outcomes
of laparoscopic radical cystectomy (LRC) in patients with previous abdominal
surgery (PAS). METHODS: We retrospectively reviewed 243 patients undergoing open
radical cystectomy (ORC) or LRC with bilateral pelvic lymph node dissection and
urinary diversion or cutaneous ureterostomy at a single center from January 2010
to December 2015. Demographic parameters, intra-operative variables, peri
operative records, pathologic outcomes, and complication rate were reviewed to
assess the impact of PAS on peri-operative and oncologic outcomes. RESULTS:
Patients in both ORC and LRC subgroups were homogeneous in terms of demography
characteristics including age, gender, BMI, ASA score, and comorbidity. Estimated
blood loss (EBL) was higher in patients with PAS undergoing ORC compared to those
with no PAS (P = 0.008). However, there was no significant difference of EBL
among patients undergoing LRC with or without PAS (P = 0.896). There was no
statistical difference in peri-operative parameters and pathological outcomes.
Patients with PAS undergoing ORC and ileal conduit had a higher vascular injury
rate (P = 0.017). Comparing patients with PAS performed by LRC and ORC, the
number of patients with the vascular injury was higher in ORC groups regardless
of the type of diversion (ileal conduit, P = 0.001, cutaneous ureterostomy, P =
0.025). There is no significant difference in other complications. CONCLUSION:
The presence of adhesions from PAS is not a contraindication to LRC. Patients
with PAS may benefit from LRC with lower estimated blood loss, fewer transfusion
rates, and vascular injuries. Furthermore, the overall oncologic outcomes and
complication rate are similar between LRC and ORC patients with PAS.
PMID- 29343303
TI - Comparison of modified wet suction technique and dry suction technique in
endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for solid lesions:
study protocol for a randomized controlled trial.
AB - BACKGROUND: Several suction techniques have been developed recently to enhance
tissue acquisition when sampling solid lesions using endoscopic ultrasound-guided
fine-needle aspiration (EUS-FNA). The aim of this study is to determine whether a
new modified wet suction technique (MWST) compared with the conventional dry
suction technique (DRST) shall present better outcomes with respect to diagnostic
yield and specimen quality of solid lesions in the intra-abdomen and mediastinum.
METHODS/DESIGN: This is a single-blind, randomized, controlled, superiority trial
conducted at four large tertiary care centers in China. Two hundred and ninety
six patients with solid lesions referred for EUS-FNA will be randomly assigned to
group A, using DRST for the first pass, or group B, using MWST for the first pass
in a ratio of 1:1. Following a 2 * 2 cross-over design, the pass sequence for
group A is DRST, MWST, DRST, MWST. For group B, the pass sequence is MWST, DRST,
MWST, DRST. All procedures will be performed by experienced echoendoscopists, and
the patients and assessors (cytologists and pathologists) will be blinded during
the entire study. The primary outcome measure is the diagnosis yield. Secondary
outcome measures are specimen quality, including assessment of quantity of cell,
tissue integrity, and blood contamination. DISCUSSION: To our knowledge, this is
the first large-scale randomized controlled trial to compare MWST with DRST when
sampling solid lesions in the intra-abdomen and mediastinum. The results may
contribute to future multicenter clinical trials in standardizing suction
techniques during EUS-FNA. TRIAL REGISTRATION: Clinical Trials.gov, NCT02789371 .
Retrospectively registered on 6 June 2016.
PMID- 29343304
TI - Increasing incidence of Dirofilaria immitis in dogs in USA with focus on the
southeast region 2013-2016.
AB - BACKGROUND: A recent American Heartworm Society (AHS) survey on the incidence of
adult heartworm infections in dogs in the United States of America showed a 21.7%
increase in the average cases per veterinary clinic from 2013 to 2016. The
analysis reported here was performed to see if heartworm testing results
available via the Companion Animal Parasite Council (CAPC) aligned with the AHS
survey and whether changes in heartworm preventive dispensing accounts for the
increased incidence. The resistance of Dirofilaria immitis to macrocyclic
lactones (MLs) has been previously reported. METHODS: An analysis of 7-9 million
heartworm antigen tests reported annually to the Companion Animal Parasite
Council (CAPC) from 2013 to 2016 was conducted and compared to the 2016 AHS
survey. A state-by-state analysis across the southeastern USA was also performed.
National heartworm preventive dispensing data were obtained from Vetstreet LLC
and analyzed. All oral, topical and injectable heartworm preventives were
included in this analysis, with injectable moxidectin counting as six doses.
RESULTS: Positive antigen tests increased by 15.28% from 2013 to 2016, similar to
the 21.7% increase reported by the AHS survey. Incidence in the southeastern USA
increased by17.9% while the rest of USA incidence increased by 11.4%. State-by
state analysis across the southeastern USA revealed an increased positive test
frequency greater than 10% in 9 of 12 states evaluated. During this time, the
overall proportion of dogs receiving heartworm prophylaxis remained relatively
unchanged. Approximately 2/3 of the dogs in the USA received no heartworm
prevention each year. CONCLUSION: These CAPC data show the rate of positive
heartworm tests increasing significantly (P < 0.0001) in the USA from 2013 to
2016, with a higher rate of increase in the southeastern USA than nationally.
Only 1/3 of dogs in the USA were dispensed one or more doses of heartworm
prevention annually by veterinarians, averaging 8.6 monthly doses/year.
Veterinarians and pet owners should work together to follow CAPC and AHS
guidelines to protect dogs from infection with D. immitis. Lack of preventive use
and the emergence of heartworm resistance to MLs could both be impacting the
increased rate of positive heartworm tests in dogs.
PMID- 29343305
TI - Relationship between Eustachian tube dysfunction and otitis media with effusion
in radiotherapy patients.
AB - OBJECTIVE: This study evaluated the relationship between radiation and Eustachian
tube dysfunction, and examined the radiation dose required to induce otitis media
with effusion. METHODS: The function of 36 Eustachian tubes in 18 patients with
head and neck cancer were examined sonotubometrically before, during, and 1, 2
and 3 months after, intensity-modulated radiotherapy. Patients with an increase
of 5 dB or less in sound pressure level (dB) during swallowing were categorised
as being in the dysfunction group. Additionally, radiation dose distributions
were assessed in all Eustachian tubes using three dose-volume histogram
parameters. RESULTS: Twenty-two of 25 normally functioning Eustachian tubes
before radiotherapy (88.0 per cent) shifted to the dysfunction group after
therapy. All ears that developed otitis media with effusion belonged to the
dysfunction group. The radiation dose threshold evaluation revealed that ears
with otitis media with effusion received significantly higher doses to the
Eustachian tubes. CONCLUSION: The results indicate a relationship between
radiation dose and Eustachian tube dysfunction and otitis media with effusion.
PMID- 29343307
TI - INFORMED CHOICE AND FEMALE STERILIZATION IN SOUTH ASIA AND LATIN AMERICA.
AB - Globally, female sterilization is one of the most popular contraceptive methods
despite concerns about quality of care for women who report being sterilized. In
this study, informed choice among sterilized women was quantified using
Demographic and Health Survey (DHS) data from 2000 to 2012 for countries in South
Asia and Latin America. Three responses measured informed choice and knowledge
about whether women were informed by a health worker or provider: that
sterilization is permanent, the potential side-effects of sterilization and other
methods of contraception. An ascending composite Method Information Index with
scores ranging from 0 (women received no information) to 3 (women received
information across all three indicators) was used. Using ordinal logistic
regression analysis, the results indicated that women younger than 25 and older
than 35 at the time of sterilization, and those at high parities, had lower odds
of a high score on the index, while the opposite was true for women sterilized in
the private sector in Latin America. Educated women in India had higher odds of a
high score on the index, while the same was true for educated and wealthy women
in Colombia. These findings indicate that not enough health care providers spend
time informing women in South Asia and Latin America about different aspects of
sterilization, and that there are specific groups of women that are more
affected. There is an urgent need to improve quality of care within health
systems providing sterilization for this very important and effective type of
contraception.
PMID- 29343306
TI - Nasal changes associated with exercise in athletes: systematic review.
AB - BACKGROUND: The prevalence of rhinitis in athletes has frequently been studied in
combination with asthma, but the impact of exercise on the paracrine and
secretory functions of nasal mucosa is less well established. This systematic
review aimed to examine the effect of exercise on nasal mucosa in elite athletes.
METHOD: A systematic search of Medline, Embase and the non-Medline subset of
PubMed, from inception to 8th March 2016, was performed to identify studies on
rhinitis in athletes. RESULTS: Of the 373 identified unique articles, a total of
8 studies satisfied the criteria for this review. CONCLUSION: There is no
evidence in the existing literature that indicates a reduction in nasal airway
induced by exercise. Olfaction and mucociliary transport time are affected in
swimmers, which can likely be attributed to chlorine irritation and which
resolves with training cessation. Short-term strenuous exercise may trigger
changes in cytology and prolonged mucociliary transport time, which also resolve
quickly with rest.
PMID- 29343308
TI - Invited review: Genomic selection for small ruminants in developed countries: how
applicable for the rest of the world?
AB - Improved management and use of estimated breeding values in breeding programmes,
have resulted in rapid genetic progress for small ruminants (SR) in Europe and
other developed countries. The development of single nucleotide polymorphisms
chips opened opportunities for genomic selection (GS) in SR in these countries.
Initially focused on production traits (growth and milk), GS has been extended to
functional traits (reproductive performance, disease resistance and meat
quality). The GS systems have been characterized by smaller reference populations
compared with those of dairy cattle and consisting mostly of cross- or multi
breed populations. Molecular information has resulted in gains in accuracy of
between 0.05 and 0.27 and proved useful in parentage verification and the
identification of QTLs for economically important traits. Except for a few
established breeds with some degree of infrastructure, the basic building blocks
to support conventional breeding programmes in small holder systems are lacking
in most developing countries. In these systems, molecular data could offer quick
wins in undertaking parentage verification and genetic evaluations using G
matrix, and determination of breed composition. The development of next
generation molecular tools has prompted investigations on genome-wide signatures
of selection for mainly adaptive and reproduction traits in SR in developing
countries. Here, the relevance of the developments and application of GS and
other molecular tools in developed countries to developing countries context is
examined. Worth noting is that in the latter, the application of GS in SR will
not be a 'one-size fits all' scenario. For breeds with some degree of
conventional genetic improvement, classical GS may be feasible. In small holder
systems, where production is key, community-based breeding programmes can provide
the framework to implement GS. However, in fragile growth systems, for example
those found in marginal environments, innovative GS to maximize adaptive
diversity will be required. A cost-benefit analysis should accompany any strategy
of implementing GS in these systems.
PMID- 29343309
TI - Could seasonal allergy be a risk factor for acute rhinosinusitis in children?
AB - OBJECTIVE: To evaluate the incidence of acute rhinosinusitis in children with
grass pollen induced rhinitis during the period of grass pollinosis. METHODS:
Children with nasal symptoms from grass pollen induced rhinitis but without
rhinosinusitis symptoms were selected. Their parents were asked to complete a
diary during pollen exposure to report nasal symptoms and drugs used daily. When
rhinosinusitis was suspected, the confirmatory diagnosis of acute rhinosinusitis
was made by fibro-endoscopy. Children without inhalant allergy served as
controls. RESULTS: Seventeen out of 242 children (7.0 per cent) had a diagnosis
of acute rhinosinusitis, confirmed by fibro-endoscopy, during grass pollination,
compared to 3 out of 65 (4.6 per cent) in the control group (p = 0.49). Among
allergic children, those with acute rhinosinusitis had symptoms for a greater
number of days and/or a higher symptoms score than children without acute
rhinosinusitis. CONCLUSION: Children with grass pollen induced rhinitis during
exposure to pollen have an incidence of endoscopically confirmed acute
rhinosinusitis comparable to non-allergic children. This suggests that grass
pollen induced rhinitis is a negligible risk factor for acute rhinosinusitis.
PMID- 29343310
TI - Effect of dietary fish oil on selected inflammatory markers in pigs.
AB - The present study tested a hypothesis that dietary fish oil (eicosapentaenoic
acid+docosahexaenoic acid) in a commonly achievable dose ameliorates a systemic
inflammation in pigs. Two groups of pigs of 16 animals each were fed a diet with
either 2.5% of fish oil (F) or a control diet with 2.5% of palm oil (P). After 70
days of fattening, eight F and eight P pigs were challenged (F+; P+) i.v. by
lipopolysaccharide. After 3 h, all pigs were sacrificed and blood, liver and
visceral adipose tissue (VAT) samples were taken. No significant effect (P>0.05)
of dietary oil on the feed intake and daily weight gain was found out. Less
neutrophils (16.8% v. 28.8%; P0.05) between F+ and P+ pigs in the peroxisome
proliferator-activated receptor gamma, GPR120, Adipor1 and Adipor2 (adiponectin
receptor) gene expression, respectively, was established; plasma adiponectin was
the same (21.1 ng/ml) in F+ and P+ pigs. In comparison with the P+ pigs,
increased expression of the lipopolysaccharide-binding protein (LBP) gene and
intercellular adhesion molecule 1 (ICAM1) gene was found out in the liver of the
F+ pigs; expression of the tumor necrosis factor alpha (TNFalpha) gene was higher
in the liver but lower in the VAT of the F+ pigs (P<0.05). The F+ pigs had higher
(P<0.05) plasma concentration of both anti-inflammatory cytokine interleukin-4
(0.46 v. 0.04 ng/ml) and pro-inflammatory TNF-alpha (13.41 v. 7.72 ng/ml). It was
concluded that dietary fish oil at the tested amount had a negligible effect on
expression of the evaluated receptor genes and plasma adiponectin, and had an
ambiguous effect on expression of cytokine genes and plasma cytokine levels.
PMID- 29343311
TI - Decompensated labyrinthine weakness presenting as de novo peripheral vertigo: a
discrete clinical entity?
AB - OBJECTIVE: A distinct subgroup of patients, presenting with apparently
spontaneous onset of vertigo, is described. RESULTS: Although vestibular
evaluation revealed caloric weakness, the proximate cause of vertigo was not
labyrinthine dysfunction, but rather the loss of vestibular compensation for an
older and previously compensated labyrinthine injury. CONCLUSION: Instead of
addressing the vestibular weakness, effective management needs to focus on the
condition that has caused the loss of compensation.
PMID- 29343312
TI - Fecal Microbiota Transplant for Multidrug-Resistant Organism Decolonization
Administered During Septic Shock.
PMID- 29343313
TI - Eucalyptus leaves powder, antibiotic and probiotic addition to broiler diets:
effect on growth performance, immune response, blood components and carcass
traits.
AB - The study was conducted to investigate the effects of different levels of
eucalyptus powder (EP), virginiamycin and probiotic on performance, immunity,
blood components and carcass traits of broiler chickens. A total of 250, 1-day
old male broiler chickens (Ross 308) were randomly allocated to five treatments
with five replicates and 10 chicks each, as a completely randomized design. The
dietary treatments consisted of: basal diet (BD), BD+0.25% EP, BD+0.5% EP,
BD+0.01% of diet probiotic (Protexin), BD+0.02% of diet antibiotic
(virginiamycin). Dietary supplementation did not affect feed intake, BW gain
(BWG) and feed conversion ratio (FCR) during starter and grower phases, but BWG
and FCR were affected during the finisher and whole periods (P<0.05).The highest
BWG and lowest FCR were obtained in birds fed with virginiamycin and 0.5% EP.
Dietary supplementation significantly increased the relative weight of carcass
and breast (P<0.05). Treatments had no effect on relative weights of internal
organs and small intestine except for bursa that increased by treatments.
Relative length of jejunum also increased by treatments (P<0.05). Antibody
production against sheep red blood cells did not changed in primary titer (day
35), but it significantly increased in secondary titer (day 42) by 0.5% EP. White
blood cell counts were increased and cholesterol decreased by dietary
supplementation (P<0.05). In conclusion, the results of this study showed that
0.5% EP served as a useful replacement for antibiotic and would improve
performance and immune response of broiler chickens.
PMID- 29343314
TI - Cell-free DNA: the role in pathophysiology and as a biomarker in kidney diseases.
AB - Cell-free DNA (cfDNA) is present in various body fluids and originates mostly
from blood cells. In specific conditions, circulating cfDNA might be derived from
tumours, donor organs after transplantation or from the foetus during pregnancy.
The analysis of cfDNA is mainly used for genetic analyses of the source tissue
tumour, foetus or for the early detection of graft rejection. It might serve also
as a nonspecific biomarker of tissue damage in critical care medicine. In kidney
diseases, cfDNA increases during haemodialysis and indicates cell damage. In
patients with renal cell carcinoma, cfDNA in plasma and its integrity is studied
for monitoring of tumour growth, the effects of chemotherapy and for prognosis.
Urinary cfDNA is highly fragmented, but the technical hurdles can now be overcome
and urinary cfDNA is being evaluated as a potential biomarker of renal injury and
urinary tract tumours. Beyond its diagnostic application, cfDNA might also be
involved in the pathogenesis of diseases affecting the kidneys as shown for
systemic lupus, sepsis and some pregnancy-related pathologies. Recent data
suggest that increased cfDNA is associated with acute kidney injury. In this
review, we discuss the biological characteristics, sources of cfDNA, its
potential use as a biomarker as well as its role in the pathogenesis of renal and
urinary diseases.
PMID- 29343315
TI - Subclinical inflammation affects iron and vitamin A but not zinc status
assessment in Senegalese children and Cambodian children and women.
AB - OBJECTIVE: To assess the impact of the acute-phase response (APR) during
inflammation on Fe, Zn and vitamin A biomarkers to allow accurate evaluation of
micronutrient status in populations. DESIGN: Ferritin (FER), soluble transferrin
receptor (TfR), retinol-binding protein (RBP), Zn, alpha1-acid glycoprotein and C
reactive protein concentrations were measured. Correction factors (CF) for each
biomarker were calculated as the ratio for groups at different stages of
inflammation v. the reference group without
inflammation.Setting/SubjectsSenegalese (n 594) and Cambodian schoolchildren (n
2471); Cambodian women of reproductive age (n 2117). RESULTS: TfR was higher
during the incubation phase (CF=1.17) and lower during early and late
convalescence (CF=0.87 and 0.78). FER was higher during all phases (CF=0.83, 0.48
and 0.65, respectively). RBP was higher during incubation (CF=0.88) and lower
during early convalescence (CF=1.21). No effect of inflammation on Zn status was
found. CONCLUSIONS: Inflammation led to overestimation of Fe status and
underestimation of vitamin A status. The response of the biomarker for vitamin A
status to inflammation depended on the vitamin A status of the populations.
Surprisingly, the assessment of Zn status was hardly affected by inflammation.
Different phases of the APR had opposite effects on the assessment of Fe status
using TfR. More research is needed to define the correct methods to adjust for
inflammation in nutritional studies.
PMID- 29343316
TI - Black soldier fly larva fat inclusion in finisher broiler chicken diet as an
alternative fat source.
AB - The objective of the present study was to evaluate the effects of partial or
total replacement of finisher diet soybean oil with black soldier fly (Hermethia
illucens L.; HI) larva fat on the growth performance, carcass traits, blood
parameters, intestinal morphology and histological features of broiler chickens.
At 21 days of age, a total of 120 male broiler chickens (Ross 308) were randomly
allocated to three experimental groups (five replicates and eight birds/pen). To
a basal control diet (C; 68.7 g/kg as fed of soybean oil), either 50% or 100% of
the soybean oil was replaced with HI larva fat (HI50 and HI100 group,
respectively). Growth performance was evaluated throughout the trial. At day 48,
15 birds (three birds/pen) per group were slaughtered at a commercial abattoir.
Carcass yield and proportions of carcass elements were recorded. Blood samples
were taken from each slaughtered chicken for haematochemical index determination.
Morphometric analyses were performed on the duodenum, jejunum and ileum. Samples
of liver, spleen, thymus, bursa of fabricius, kidney and heart were submitted to
histological investigations. Growth performance, carcass traits, haematochemical
parameters and gut morphometric indexes were not influenced by the dietary
inclusion of HI larva fat. Histopathological alterations developed in the spleen,
thymus, bursa of fabricius and liver and were identified in all of the
experimental groups, but HI larva fat inclusion did not significantly affect
(P>0.05) the severity of the histopathological findings. The present study
suggests that 50% or 100% replacement of soybean oil with HI larva fat in broiler
chickens diets has no adverse effects on growth performance or blood parameters
and had no beneficial effect on gut health.
PMID- 29343317
TI - Disaster-Relief Fraud: A Dark Side of Disasters.
PMID- 29343407
TI - A Flat Pink Plaque On The Right Anterior Forearm.
PMID- 29343408
TI - Response to 'Perilesional edema in brain cancer: Independent prognosticator or
epiphenomenon of biomolecular signature?'
PMID- 29343409
TI - Monitoring early changes in rectal tumor morphology and volume during 5 weeks of
preoperative chemoradiotherapy - An evaluation with sequential MRIs.
AB - PURPOSE: To assess early changes in rectal tumor volume and morphology on
sequential MRIs performed during 5 weeks of chemoradiotherapy. MATERIALS AND
METHODS: Thirteen patients underwent weekly T2W-MRI during 5 weeks of
preoperative radiotherapy (total 50 Gy), starting after the first week of
radiation. Two radiologists visually evaluated tumor volume and morphology and
one reader manually segmented tumors for each time point to quantitatively
calculate tumor volumes. Evolution in tumor volume/morphology was assessed over
time and compared between good responders (tumor regression grade (TRG) 1-2) and
poor responders (TRG 3-5). RESULTS: Tumor volumes decreased significantly during
radiation. Early signs of response were also visually apparent: in the majority
of good responders an early fibrotic transformation (week 2-3) as well as a
visually estimated early volume reduction of >1/3 (week 1-2), was observed while
these early changes only occurred in a minority of poor responders. CONCLUSION:
Results of this exploratory pilot study suggest that changes in rectal tumor
morphology (fibrosis) and volume can already be observed early during radiation,
both when measured quantitatively and when assessed visually. These changes
appear to be indicative of the final treatment outcome.
PMID- 29343410
TI - Random uncertainty of photometric determination of hemolysis index on the Abbott
Architect c16000 platform.
AB - BACKGROUND: Automatic photometric determination of the hemolysis index (HI) on
serum and plasma samples is central to detect potential interferences of in vitro
hemolysis on laboratory tests. When HI is above an established cut-off for
interference, results may suffer from a significant bias and undermine clinical
reliability of the test. Despite its undeniable importance for patient safety,
the analytical performance of HI estimation is not usually checked in
laboratories. Here we evaluated for the first time the random source of
measurement uncertainty of HI determination on the two Abbott Architect c16000
platforms in use in our laboratory. METHODS: From January 2016 to September 2017,
we collected data from daily photometric determination of HI on a fresh-frozen
serum pool with a predetermined HI value of ~100 (corresponding to ~1g/L of free
hemoglobin). Monthly and cumulative CVs were calculated. RESULTS: During
21months, 442 and 451 measurements were performed on the two platforms,
respectively. Monthly CVs ranged from 0.7% to 2.7% on c16000-1 and from 0.8% to
2.5% on c16000-2, with a between-platform cumulative CV of 1.82% (corresponding
to an expanded uncertainty of 3.64%). Mean HI values on the two platforms were
just slightly biased (101.3 vs. 103.1, 1.76%), but, due to the high precision of
measurements, this difference assumed statistical significance (p<0.0001).
CONCLUSIONS: Even though no quality specifications are available to date, our
study shows that the HI measurement on Architect c16000 platform has nice
reproducibility that could be considered in establishing the state of the art of
the measurement.
PMID- 29343411
TI - Consequence of enhanced LC3-trafficking for a live, attenuated M. tuberculosis
vaccine.
AB - Development of a new vaccine against tuberculosis is urgently needed. Recent work
has demonstrated that two related LC3-associated trafficking pathways, autophagy
and LC3-associated phagocytosis (LAP), enhance antigen presentation and might
play a role in vaccine efficacy. Mycobacterium tuberculosis inhibits both LC3
trafficking pathways. Moreover, the vaccine strain, BCG, induces even less LC3
trafficking than M. tuberculosis, which may help explain its limited efficacy. To
determine whether enhanced LC3-trafficking can improve efficacy of a live,
attenuated M. tuberculosis vaccine, we took advantage of our recent finding that
the bacterial virulence factor CpsA inhibits LAP. When we deleted cpsA in the
mc26206 vaccine strain, it dramatically increased LC3-trafficking. We compared
the protective efficacy of the strain lacking cpsA to the parent strain and to
BCG in mice challenged with M. tuberculosis. We found that the strain lacking
cpsA generated modestly enhanced protection in the spleen, but overall did not
outperform BCG.
PMID- 29343413
TI - Exposure to and colonisation by antibiotic-resistant E. coli in UK coastal water
users: Environmental surveillance, exposure assessment, and epidemiological study
(Beach Bum Survey).
AB - BACKGROUND: Antibiotic-resistant bacteria (ARB) present a global public health
problem. With numbers of community-acquired resistant infections increasing,
understanding the mechanisms by which people are exposed to and colonised by ARB
can help inform effective strategies to prevent their spread. The role natural
environments play in this is poorly understood. This is the first study to
combine surveillance of ARB in bathing waters, human exposure estimates and
association between exposure and colonisation by ARB in water users. METHODS: 97
bathing water samples from England and Wales were analysed for the proportion of
E. coli harbouring blaCTX-M. These data were used to estimate the likelihood of
water users ingesting blaCTX-M-bearing E. coli. Having identified surfers as
being at risk of exposure to ARB, a cross-sectional study was conducted. Regular
surfers and non-surfers were recruited to assess whether there is an association
between surfing and gut colonisation by blaCTX-M-bearing E. coli. RESULTS: 11 of
97 bathing waters sampled were found to contain blaCTX-M-bearing E. coli. While
the percentage of blaCTX-M-bearing E. coli in bathing waters was low (0.07%),
water users are at risk of ingesting these ARB. It is estimated that over 2.5
million water sports sessions occurred in 2015 resulting in the ingestion of at
least one blaCTX-M-bearing E. coli. In the epidemiological survey, 9/143 (6.3%)
surfers were colonised by blaCTX-M-bearing E. coli, as compared to 2/130 (1.5%)
of non-surfers (risk ratio=4.09, 95% CI 1.02 to 16.4, p=0.046). CONCLUSIONS:
Surfers are at risk of exposure to and colonisation by clinically important
antibiotic-resistant E. coli in coastal waters. Further research must be done on
the role natural environments play in the transmission of ARB.
PMID- 29343414
TI - Oxaliplatin and neuropathy: A role for sodium channels.
PMID- 29343412
TI - Implementing genome-driven personalized cardiology in clinical practice.
AB - Genomics designates the coordinated investigation of a large number of genes in
the context of a biological process or disease. It may be long before we attain
comprehensive understanding of the genomics of common complex cardiovascular
diseases (CVDs) such as inherited cardiomyopathies, valvular diseases, primary
arrhythmogenic conditions, congenital heart syndromes, hypercholesterolemia and
atherosclerotic heart disease, hypertensive syndromes, and heart failure with
preserved/reduced ejection fraction. Nonetheless, as genomics is evolving
rapidly, it is constructive to survey now pertinent concepts and breakthroughs.
Today, clinical multimodal electronic medical/health records (EMRs/EHRs)
incorporating genomic information establish a continuously-learning, vast
knowledge-network with seamless cycling between clinical application and
research. It can inform insights into specific pathogenetic pathways, guide
biomarker-assisted precise diagnoses and individualized treatments, and stratify
prognoses. Complex CVDs blend multiple interacting genomic variants, epigenetics,
and environmental risk-factors, engendering progressions of multifaceted disease
manifestations, including clinical symptoms and signs. There is no straight-line
linkage between genetic cause(s) or causal gene-variant(s) and disease
phenotype(s). Because of interactions involving modifier-gene influences, (micro)
environmental, and epigenetic effects, the same variant may actually produce
dissimilar abnormalities in different individuals. Implementing genome-driven
personalized cardiology in clinical practice reveals that the study of CVDs at
the level of molecules and cells can yield crucial clinical benefits.
Complementing evidence-based medicine guidelines from large ("one-size fits all")
randomized controlled trials, genomics-based personalized or precision cardiology
is a most-creditable paradigm: It provides customizable approaches to prevent,
diagnose, and manage CVDs with treatments directly/precisely aimed at causal
defects identified by high-throughput genomic technologies. They encompass stem
cell and gene therapies exploiting CRISPR-Cas9-gene-editing, and metabolomic
pharmacogenomic therapeutic modalities, precisely fine-tuned for the individual
patient. Following the Human Genome Project, many expected genomics technology to
provide imminent solutions to intractable medical problems, including CVDs. This
eagerness has reaped some disappointment that advances have not yet materialized
to the degree anticipated. Undoubtedly, personalized genetic/genomics testing is
an emergent technology that should not be applied without supplementary
phenotypic/clinical information: Genotype?Phenotype. However, forthcoming
advances in genomics will naturally build on prior attainments and, combined with
insights into relevant epigenetics and environmental factors, can plausibly
eradicate intractable CVDs, improving human health and well-being.
PMID- 29343415
TI - Paradigms for restoration of somatosensory feedback via stimulation of the
peripheral nervous system.
AB - The somatosensory system contributes substantially to the integration of multiple
sensor modalities into perception. Tactile sensations, proprioception and even
temperature perception are integrated to perceive embodiment of our limbs. Damage
of somatosensory networks can severely affect the execution of daily life
activities. Peripheral injuries are optimally corrected via direct interfacing of
the peripheral nerves. Recent advances in implantable devices, stimulation
paradigms, and biomimetic sensors enabled the restoration of natural sensations
after amputation of the limb. The refinement of stimulation patterns to deliver
natural feedback that can be interpreted intuitively such to prescind from long
learning sessions is crucial to function restoration. For this review, we
collected state-of-the-art knowledge on the evolution of stimulation paradigms
from single fiber stimulation to the eliciting of multisensory sensations. Data
from the literature are structured into six sections: (a) physiology of the
somatosensory system; (b) stimulation of single fibers; (c) restoral of
multisensory percepts; (d) closure of the control loop in hand prostheses; (e)
sensory restoration and the sense of embodiment, and (f) methodologies to assess
stimulation outcomes. Full functional recovery demands further research on
multisensory integration and brain plasticity, which will bring new paradigms for
intuitive sensory feedback in the next generation of limb prostheses.
PMID- 29343416
TI - Intrathecal tranexamic acid - an accident waiting to happen?
PMID- 29343417
TI - Does the addition of active body warming to in-line intravenous fluid warming
prevent maternal hypothermia during elective caesarean section? A randomised
controlled trial.
PMID- 29343418
TI - The combination of corticosteroid and tocolytic therapy in a preeclamptic patient
is a risk factor for the development of acute pulmonary oedema.
PMID- 29343419
TI - Successful use of non-invasive positive pressure ventilation in a patient with
the severe form of X-linked myotubular myopathy.
AB - The severity of X-linked myotubular myopathy (XLMTM) ranges from mild to severe,
depending on the level of ventilatory support required. Patients with the severe
form of XLMTM usually die within the first year of life due to respiratory
failure. Most survivors need tracheostomies, and there has only been one report
about the use of non-invasive positive pressure ventilation (NPPV) in patients
with the severe form of XLMTM because of the severity of the associated
respiratory failure. We successfully applied NPPV with high-span positive
inspiratory pressure (PIP) in a patient with the severe form of XLMTM, who also
had secondary pectus excavatum. About a year after the initiation of NPPV with
high-span PIP, the patient's pectus excavatum had improved. As the patient's
pectus excavatum improved, his respiratory disturbance was ameliorated, and the
frequency of respiratory infections gradually decreased. NPPV might be the first
choice respiratory management strategy for patients with XLMTM.
PMID- 29343421
TI - Frequency of small-colony variants and antimicrobial susceptibility of
methicillin-resistant Staphylococcus aureus in cystic fibrosis patients.
AB - BACKGROUND: Small-colony variants (SCVs) are a distinct phenotype of
Staphylococcus aureus, known for their role in chronic, difficult to treat
infections, including cystic fibrosis (CF) lung disease. The goal of this study
was to characterize SCV MRSA infection in an adult and pediatric CF population
and to identify antibiotic susceptibility patterns unique to SCV MRSA. METHODS:
We recovered methicillin-resistant S. aureus (MRSA) from respiratory culture
samples from CF patients at the Johns Hopkins Hospital during a 6month study
period. RESULTS: Of 1161 samples, 200 isolates (17%) were identified as MRSA, and
37 isolates from 28 patients were identified as SCV MRSA. A higher proportion of
MRSA was found among SCV isolates (37/66, 56%) compared to normal colony variant
(NCV) isolates (163/417, 39%), p=0.02. All SCV MRSA isolates from individual
patients were susceptible to vancomycin and ceftaroline, but they demonstrated
higher rates of antibiotic resistance to trimethoprim/sulfamethoxazole,
moxifloxacin, and erythromycin, compared to NCV MRSA isolates. Additionally,
individuals with SCV MRSA had lower lung function, higher rates of persistent
MRSA infection, and higher rates of previous antibiotic use, compared to
individuals with NCV MRSA. CONCLUSIONS: A significant proportion of MRSA isolates
recovered from patients with CF have the SCV morphology. Compared to individuals
with NCV MRSA, those with SCV MRSA have higher rates of persistent MRSA infection
and lower lung function. SCV MRSA isolates were more resistant than NCV, but they
are highly susceptible to vancomycin, linezolid and ceftaroline.
PMID- 29343422
TI - Effect of foetal and infant growth and body composition on respiratory outcomes
in preterm-born children.
AB - Body composition and growth outcomes of preterm-born subjects have been studied
by many researchers. In general, preterm-born children have lower height and
weight especially in infancy. Despite showing potential for catch-up growth, they
continue to lag behind their term counterparts in adolescence and adulthood. The
various methods of studying body composition and the differing gestations and
ages at which it is assessed may go some way to explaining the inconsistent
results observed in different studies. In addition, there is a paucity of data on
the effects of foetal and infant growth and of body composition on later
respiratory outcomes. In largely term-born subjects, foetal growth and growth
trajectories appear to have differential effects on later respiratory outcomes.
Early weight gain in infancy appears to be associated with increased respiratory
symptoms in childhood but catch-up growth in infancy appears to be associated
with possible improved lung function status.
PMID- 29343420
TI - AMPK Re-Activation Suppresses Hepatic Steatosis but its Downregulation Does Not
Promote Fatty Liver Development.
AB - Nonalcoholic fatty liver disease is a highly prevalent component of disorders
associated with disrupted energy homeostasis. Although dysregulation of the
energy sensor AMP-activated protein kinase (AMPK) is viewed as a pathogenic
factor in the development of fatty liver its role has not been directly
demonstrated. Unexpectedly, we show here that liver-specific AMPK KO mice display
normal hepatic lipid homeostasis and are not prone to fatty liver development,
indicating that the decreases in AMPK activity associated with hepatic steatosis
may be a consequence, rather than a cause, of changes in hepatic metabolism. In
contrast, we found that pharmacological re-activation of downregulated AMPK in
fatty liver is sufficient to normalize hepatic lipid content. Mechanistically,
AMPK activation reduces hepatic triglyceride content both by inhibiting lipid
synthesis and by stimulating fatty acid oxidation in an LKB1-dependent manner,
through a transcription-independent mechanism. Furthermore, the effect of the
antidiabetic drug metformin on lipogenesis inhibition and fatty acid oxidation
stimulation was enhanced by combination treatment with small-molecule AMPK
activators in primary hepatocytes from mice and humans. Overall, these results
demonstrate that AMPK downregulation is not a triggering factor in fatty liver
development but in contrast, establish the therapeutic impact of pharmacological
AMPK re-activation in the treatment of fatty liver disease.
PMID- 29343423
TI - Request for HIV serology in primary care: A survey of medical and nursing
professionals.
AB - INTRODUCTION: In the Community of Madrid there is 42.7% late HIV diagnosis.
Primary care is the gateway to the health system and the frequency of serological
tests requested by these professionals is unknown. The objectives were to
establish the frequency of requests for HIV serology by medical and nursing
primary care professionals in the Community of Madrid and the factors associated
with these requests. METHOD: An 'on-line' survey was conducted, asking
professionals who participated in the evaluation study of strategies to promote
early diagnosis of HIV in primary care in the Community of Madrid (ESTVIH) about
the number of HIV-serology tests requested in the last 12 months. The association
between HIV-serology requesting and the sociodemographic and clinical practice
characteristics of the professionals was quantified using adjusted odds ratios
(aOR) according to logistic regression. RESULTS: 264 surveys (59.5% physicians).
Eighty-two point two percent of medical and 18.7% of nursing professionals
reported requesting at least one HIV-serology in the last 12 months (median: 15
and 2 HIV-serology request, respectively). The doctors associated the request
with: being male (aOR: 2.95; 95% CI: 0.82-10.56), being trained in pre-post HIV
test counselling (aOR: 2.42; 95% CI: 0.84-6.93) and the nurses with: age (<50
years; aOR: 2.75; 95% CI: 0.97-7.75), and number of years working in primary care
(>13 years; aOR: 3.02; 95% CI: 1.07-8.52). CONCLUSION: It is necessary to promote
HIV testing and training in pre-post HIV test counselling for medical and nursing
professionals in primary care centres.
PMID- 29343425
TI - Iba57p participates in maturation of a [2Fe-2S]-cluster Rieske protein and in
formation of supercomplexes III/IV of Saccharomyces cerevisiae electron transport
chain.
AB - The [Fe-S] late-acting subsystem comprised of Isa1p/Isa2p, Grx5p, and Iba57p
proteins (Fe-S-IBG subsystem) is involved in [4Fe-4S]-cluster protein assembly.
The effect of deleting IBA57 in Saccharomyces cerevisiae on mitochondrial
respiratory complex integration and functionality associated with Rieske protein
maturation was evaluated. The iba57Delta mutant showed decreased expression and
maturation of the Rieske protein. The loss of Rieske protein caused by IBA57
deletion affected the structure of supercomplexes III2IV2 and III2IV1 and their
integration into the mitochondria, causing dysfunction in the electron transport
chain. These effects were correlated with decreased cytochrome functionality and
content in the iba57Delta mutant. These findings suggest that Iba57p participates
in maturation of the [2Fe-2S]-cluster into the Rieske protein and that Rieske
protein plays important roles in the conformation and functionality of
mitochondrial supercomplex III/IV in the electron transport chain.
PMID- 29343424
TI - IGF1/MAPK/ERK signaling pathway-mediated programming alterations of adrenal
cortex cell proliferation by prenatal caffeine exposure in male offspring rats.
AB - Our previous study proposed a glucocorticoid-insulin-like growth factor 1 (GC
IGF1) axis programming mechanism for prenatal caffeine exposure (PCE)-induced
adrenal developmental dysfunction. Here, we focused on PCE-induced cell
proliferation changes of the adrenal cortex in male offspring rats before and
after birth and clarified the intrauterine programming mechanism. On gestational
day (GD) 20, the PCE group had an elevated serum corticosterone level reduced
fetal bodyweight, maximum adrenal sectional area, and elevated adrenal
corticosterone and aldosterone contents. However, in postnatal week (PW) 6, the
serum corticosterone level was decreased, and the bodyweight, with catch-up
growth, adrenal cortex maximum cross-sectional area and aldosterone content were
relatively increased, while the adrenal corticosterone content was lower. On
GD20, the expression of adrenal IGF1, IGF1R and proliferating cell nuclear
antigen (PCNA) were decreased, while the expression of these factors at PW6 were
increased in the PCE group. Fetal adrenal gene chip analysis suggested that the
mitogen-activated protein kinase/extracellular regulated protein kinase
(MAPK/ERK) signal pathway was suppressed in the PCE group. Moreover, in the rat
primary adrenal cells, corticosterone (rather than caffeine) was shown to
significantly inhibit cell proliferation, IGF1 and PCNA expression, and ERK
phosphorylation, which could be reversed by exogenous IGF1. Meanwhile, the
effects of exogenous IGF1 were reversed by the ERK pathway inhibitor (PD184161).
In conclusion, PCE could induce programming alterations in adrenal cortical cell
proliferation before and after birth in male offspring rats. The underlying
mechanism is associated with the inhibition of fetal adrenal IGF1-related
MAPK/ERK signaling pathway caused by high glucocorticoid levels.
PMID- 29343426
TI - Environmental Mycobacterium avium subsp. hominissuis have a higher probability to
act as a recipient in conjugation than clinical strains.
AB - Mycobacterium avium subsp. hominissuis (MAH) is a widespread opportunistic
pathogen that can be isolated from environment (dust, soil and water) and
patients with lung or lymphnode infection. In our previous research we revealed
the pronounced genetic diversity in MAH by identifying eight different types of a
newly described genomic island. In order to identify mechanisms of such
horizontal gene transfer we now analyzed the ability of 47 MAH isolates to
inherit the conjugative plasmid pRAW from M. marinum. A higher percentage of
environmental isolates (22.7%) compared to clinical isolates (8%) had the
capacity to function as recipient in conjugal plasmid transfer. Genetic analysis
showed additionally that environmental isolates contained more genes homologous
to genes present on conjugative mycobacterial plasmids than clinical isolates.
Comparative analysis of the genomes of the isolates pointed to a possible
association between the ability to act as recipient in conjugation and the
structure of a genomic region containing the radC gene and a type I
restriction/modification system. Finally we found that uptake of pRAW decreased
the resistance against various antibiotics.
PMID- 29343427
TI - Controlled attenuation parameter and alcoholic hepatic steatosis: Diagnostic
accuracy and role of alcohol detoxification.
AB - BACKGROUND & AIMS: Controlled attenuation parameter (CAP) is a novel non-invasive
measure of hepatic steatosis, but it has not been evaluated in alcoholic liver
disease. Therefore, we aimed to validate CAP for the assessment of biopsy
verified alcoholic steatosis and to study the effect of alcohol detoxification on
CAP. METHODS: This was a cross-sectional biopsy-controlled diagnostic study in
four European liver centres. Consecutive alcohol-overusing patients underwent
concomitant CAP, regular ultrasound, and liver biopsy. In addition, we measured
CAP before and after admission for detoxification in a separate single-centre
cohort. RESULTS: A total of 562 patients were included in the study: 269 patients
in the diagnostic cohort with steatosis scores S0, S1, S2, and S3 = 77 (28%), 94
(35%), 64 (24%), and 34 (13%), respectively. CAP diagnosed any steatosis and
moderate steatosis with fair accuracy (area under the receiver operating
characteristic curve [AUC] >=S1 = 0.77; 0.71-0.83 and AUC >=S2 = 0.78; 0.72
0.83), and severe steatosis with good accuracy (AUC S3 = 0.82; 0.75-0.88). CAP
was superior to bright liver echo pattern by regular ultrasound. CAP above 290
dB/m ruled in any steatosis with 88% specificity and 92% positive predictive
value, while CAP below 220 dB/m ruled out steatosis with 90% sensitivity, but 62%
negative predictive value. In the 293 patients who were admitted 6.3 days
(interquartile range 4-6) for detoxification, CAP decreased by 32 +/- 47 dB/m (p
<0.001). Body mass index predicted higher CAP in both cohorts, irrespective of
drinking pattern. Obese patients with body mass index >=30 kg/m2 had a
significantly higher CAP, which did not decrease significantly during
detoxification. CONCLUSIONS: CAP has a good diagnostic accuracy for diagnosing
severe alcoholic liver steatosis and can be used to rule in any steatosis. In non
obese but not in obese, patients, CAP rapidly declines after alcohol withdrawal.
LAY SUMMARY: CAP is a new ultrasound-based technique for measuring fat content in
the liver, but has never been tested for fatty liver caused by alcohol. Herein,
we examined 562 patients in a multicentre setting. We show that CAP highly
correlates with liver fat, and patients with a CAP value above 290 dB/m were
highly likely to have more than 5% fat in their livers, determined by liver
biopsy. CAP was also better than regular ultrasound for determining the severity
of alcoholic fatty-liver disease. Finally, we show that three in four (non-obese)
patients rapidly decrease in CAP after short-term alcohol withdrawal. In
contrast, obese alcohol-overusing patients were more likely to have higher CAP
values than lean patients, irrespective of drinking.
PMID- 29343428
TI - Development and pre-clinical evaluation in the swine model of a mucosal vaccine
tablet for human influenza viruses: A proof-of-concept study.
AB - Liquid vaccine formulations present some disadvantages such as stability
problems, cold chain requirement or administration by trained personnel. Vaccine
formulated as tablets would present a wide range of progress such as an increase
stability that would facilitate the administration, the distribution and the
storage of vaccine formulations. This work investigates the possibility to
develop a mucosal tablet vaccine for human influenza viruses. The tablets were
tested in vitro for biological efficacy and stability and in vivo in swine as a
model for influenza A virus immunity. First, the ability to produce by compaction
a stable vaccine with a preserved antigen was demonstrated. In a second part,
vaccine tablets were used to immunize pigs. After positioning the tablets on the
buccal mucosa, the animals were challenged by inoculation of the A/H1N1 pandemic
virus. The responses were compared to those observed in animals vaccinated
intramuscularly with the commercial liquid vaccine. It was observed signs of
priming of the pig's immune system with vaccine tablets, even if the immune
response stayed lower than vaccination by intramuscular route. Thus, we present
attractive results that indicate a promising potential for mucosal vaccine
tablets.
PMID- 29343429
TI - Translational control of human acetyl-CoA carboxylase 1 mRNA is mediated by an
internal ribosome entry site in response to ER stress, serum deprivation or
hypoxia mimetic CoCl2.
AB - Acetyl-CoA carboxylase 1 (ACC1) is a cytosolic enzyme catalyzing the rate
limiting step in de novo fatty acid biosynthesis. There is mounting evidence
showing that ACC1 is susceptible to dysregulation and that it is over-expressed
in liver diseases associated with lipid accumulation and in several cancers. In
the present study, ACC1 regulation at the translational level is reported. Using
several experimental approaches, the presence of an internal ribosome entry site
(IRES) has been established in the 5' untranslated region (5' UTR) of the ACC1
mRNA. Transfection experiments with the ACC1 5' UTR inserted in a dicistronic
reporter vector show a remarkable increase in the downstream cistron translation,
through a cap-independent mechanism. The endoplasmic reticulum (ER) stress
condition and the related unfolded protein response (UPR), triggered by treatment
with thapsigargin and tunicamycin, cause an increase of the cap-independent
translation of ACC1 mRNA in HepG2 cells, despite the overall reduction in global
protein synthesis. Other stress conditions, such as serum starvation and
incubation with hypoxia mimetic agent CoCl2, up-regulate ACC1 expression in HepG2
cells at the translational level. Overall, these findings indicate that the
presence of an IRES in the ACC1 5' UTR allows ACC1 mRNA translation in conditions
that are inhibitory to cap-dependent translation. A potential involvement of the
cap-independent translation of ACC1 in several pathologies, such as obesity and
cancer, has been discussed.
PMID- 29343430
TI - Cardiolipin synthesizing enzymes form a complex that interacts with cardiolipin
dependent membrane organizing proteins.
AB - The mitochondrial glycerophospholipid cardiolipin plays important roles in
mitochondrial biology. Most notably, cardiolipin directly binds to mitochondrial
proteins and helps assemble and stabilize mitochondrial multi-protein complexes.
Despite their importance for mitochondrial health, how the proteins involved in
cardiolipin biosynthesis are organized and embedded in mitochondrial membranes
has not been investigated in detail. Here we show that human PGS1 and CLS1 are
constituents of large protein complexes. We show that PGS1 forms oligomers and
associates with CLS1 and PTPMT1. Using super-resolution microscopy, we observed
well-organized nanoscale structures formed by PGS1. Together with the observation
that cardiolipin and CLS1 are not required for PGS1 to assemble in the complex we
predict the presence of a PGS1-centered cardiolipin-synthesizing scaffold within
the mitochondrial inner membrane. Using an unbiased proteomic approach we found
that PGS1 and CLS1 interact with multiple cardiolipin-binding mitochondrial
membrane proteins, including prohibitins, stomatin-like protein 2 and the MICOS
components MIC60 and MIC19. We further mapped the protein-protein interaction
sites between PGS1 and itself, CLS1, MIC60 and PHB. Overall, this study provides
evidence for the presence of a cardiolipin synthesis structure that transiently
interacts with cardiolipin-dependent protein complexes.
PMID- 29343431
TI - Gasdermin D Flashes an Exit Signal for IL-1.
AB - The IL-1 family of cytokines follows an unconventional pathway of secretion
mostly associated with inflammatory cell death. In this issue of Immunity,
(Evavold et al., 2017) report gasdermin D pores as channels for active IL-1
release in live phagocytic cells.
PMID- 29343432
TI - HIV Immunogens: Affinity Is Key.
AB - Generation of broadly neutralizing antibodies is a key aim of HIV vaccine design,
but the precursor B cells are rare. Abbott et al. (2018) report that high
affinity and avidity immunogens are required to promote maturation of low
frequency B cells in germinal centers.
PMID- 29343434
TI - A Long-Distance Relay-tionship between Tumor and Bone.
AB - Myeloid cells, including neutrophils, are important regulators of tumor growth
and metastasis. In Science, Engblom et al. (2017) reveal how lung tumors remotely
engage bone-resident cells through a relay mechanism that achieves a sustained
supply of tumor-promoting neutrophils.
PMID- 29343433
TI - Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue
Inducing Function of Innate Lymphoid Cells and Colonic Inflammation.
AB - Group 3 innate lymphoid cells (ILC3s) sense environmental signals and are
critical for tissue integrity in the intestine. Yet, which signals are sensed and
what receptors control ILC3 function remain poorly understood. Here, we show that
ILC3s with a lymphoid-tissue-inducer (LTi) phenotype expressed G-protein-coupled
receptor 183 (GPR183) and migrated to its oxysterol ligand 7alpha,25
hydroxycholesterol (7alpha,25-OHC). In mice lacking Gpr183 or 7alpha,25-OHC,
ILC3s failed to localize to cryptopatches (CPs) and isolated lymphoid follicles
(ILFs). Gpr183 deficiency in ILC3s caused a defect in CP and ILF formation in the
colon, but not in the small intestine. Localized oxysterol production by
fibroblastic stromal cells provided an essential signal for colonic lymphoid
tissue development, and inflammation-induced increased oxysterol production
caused colitis through GPR183-mediated cell recruitment. Our findings show that
GPR183 promotes lymphoid organ development and indicate that oxysterol-GPR183
dependent positioning within tissues controls ILC3 activity and intestinal
homeostasis.
PMID- 29343436
TI - Motile Collectors: Platelets Promote Innate Immunity.
AB - Platelets migrate in vitro but the significance of platelet migration in vivo
remains unclear. In a recent issue of Cell, Gaertner et al. (2017) demonstrate
that active platelet migration in vivo promotes mechano-scavenging of bacterial
pathogens and neutrophil activation.
PMID- 29343435
TI - Paracrine Wnt5a-beta-Catenin Signaling Triggers a Metabolic Program that Drives
Dendritic Cell Tolerization.
AB - Despite recent advances, many cancers remain refractory to available
immunotherapeutic strategies. Emerging evidence indicates that the tolerization
of local dendritic cells (DCs) within the tumor microenvironment promotes immune
evasion. Here, we have described a mechanism by which melanomas establish a site
of immune privilege via a paracrine Wnt5a-beta-catenin-peroxisome proliferator
activated receptor-gamma (PPAR-gamma) signaling pathway that drives fatty acid
oxidation (FAO) in DCs by upregulating the expression of the carnitine
palmitoyltransferase-1A (CPT1A) fatty acid transporter. This FAO shift increased
the protoporphyrin IX prosthetic group of indoleamine 2,3-dioxgenase-1 (IDO)
while suppressing interleukin(IL)-6 and IL-12 cytokine expression, culminating in
enhanced IDO activity and the generation of regulatory T cells. We demonstrated
that blockade of this pathway augmented anti-melanoma immunity, enhanced the
activity of anti-PD-1 antibody immunotherapy, and suppressed disease progression
in a transgenic melanoma model. This work implicates a role for tumor-mediated
metabolic reprogramming of local DCs in immune evasion and immunotherapy
resistance.
PMID- 29343437
TI - Memory B Cells that Cross-React with Group 1 and Group 2 Influenza A Viruses Are
Abundant in Adult Human Repertoires.
AB - Human B cell antigen-receptor (BCR) repertoires reflect repeated exposures to
evolving influenza viruses; new exposures update the previously generated B cell
memory (Bmem) population. Despite structural similarity of hemagglutinins (HAs)
from the two groups of influenza A viruses, cross-reacting antibodies (Abs) are
uncommon. We analyzed Bmem compartments in three unrelated, adult donors and
found frequent cross-group BCRs, both HA-head directed and non-head directed.
Members of a clonal lineage from one donor had a BCR structure similar to that of
a previously described Ab, encoded by different gene segments. Comparison showed
that both Abs contacted the HA receptor-binding site through long heavy-chain
third complementarity determining regions. Affinities of the clonal-lineage BCRs
for historical influenza-virus HAs from both group 1 and group 2 viruses
suggested that serial responses to seasonal influenza exposures had elicited the
lineage and driven affinity maturation. We propose that appropriate immunization
regimens might elicit a comparably broad response.
PMID- 29343439
TI - The Family of LPS Signal Transducers Increases: the Arrival of Chanzymes.
AB - After LPS recognition, the MyD88-dependent and the TRIF-dependent pathways are
consecutively activated in macrophages. Schappe et al. (2018) show that the
chanzyme TRPM7 is required for an efficient LPS receptor complex endosomal
relocation and the activation of the TRIF pathway.
PMID- 29343441
TI - moDCs, Less Problems.
AB - Type 1 conventional dendritic cells are necessary for the development of anti
tumor immunity. In this issue of Immunity, Sharma et al. (2018) identify a
phenotypically similar monocyte-derived population within inflamed tumors that
promotes T cell responses during therapy.
PMID- 29343438
TI - Regulation of the Immune Response by the Aryl Hydrocarbon Receptor.
AB - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
that is activated by small molecules provided by the diet, microorganisms,
metabolism, and pollutants. AhR is expressed by a number of immune cells, and
thus AhR signaling provides a molecular pathway that integrates the effects of
the environment and metabolism on the immune response. Studies have shown that
AhR signaling plays important roles in the immune system in health and disease.
As its activity is regulated by small molecules, AhR also constitutes a potential
target for therapeutic immunomodulation. In this review we discuss the role of
AhR in the regulation of the immune response in the context of autoimmunity,
infection, and cancer, as well as the potential opportunities and challenges of
developing AhR-targeted therapeutics.
PMID- 29343440
TI - Chanzyme TRPM7 Mediates the Ca2+ Influx Essential for Lipopolysaccharide-Induced
Toll-Like Receptor 4 Endocytosis and Macrophage Activation.
AB - Toll-like receptors (TLRs) sense pathogen-associated molecular patterns to
activate the production of inflammatory mediators. TLR4 recognizes
lipopolysaccharide (LPS) and drives the secretion of inflammatory cytokines,
often contributing to sepsis. We report that transient receptor potential
melastatin-like 7 (TRPM7), a non-selective but Ca2+-conducting ion channel,
mediates the cytosolic Ca2+ elevations essential for LPS-induced macrophage
activation. LPS triggered TRPM7-dependent Ca2+ elevations essential for TLR4
endocytosis and the subsequent activation of the transcription factor IRF3. In a
parallel pathway, the Ca2+ signaling initiated by TRPM7 was also essential for
the nuclear translocation of NFkappaB. Consequently, TRPM7-deficient macrophages
exhibited major deficits in the LPS-induced transcriptional programs in that they
failed to produce IL-1beta and other key pro-inflammatory cytokines. In accord
with these defects, mice with myeloid-specific deletion of Trpm7 are protected
from LPS-induced peritonitis. Our study highlights the importance of Ca2+
signaling in macrophage activation and identifies the ion channel TRPM7 as a
central component of TLR4 signaling.
PMID- 29343443
TI - New Job for NK Cells: Architects of the Tumor Microenvironment.
AB - NK cells control tumor growth directly through targeted cytotoxic granule release
or cytokine secretion and indirectly by orchestrating anti-tumor immune
responses. In this issue of Immunity, Glasner et al. (2018) now reveal a new role
for NK cells in preventing metastatic spread through controlling tumor
architecture.
PMID- 29343442
TI - The Transcription Factor STAT6 Mediates Direct Repression of Inflammatory
Enhancers and Limits Activation of Alternatively Polarized Macrophages.
AB - The molecular basis of signal-dependent transcriptional activation has been
extensively studied in macrophage polarization, but our understanding remains
limited regarding the molecular determinants of repression. Here we show that IL
4-activated STAT6 transcription factor is required for the direct transcriptional
repression of a large number of genes during in vitro and in vivo alternative
macrophage polarization. Repression results in decreased lineage-determining
transcription factor, p300, and RNA polymerase II binding followed by reduced
enhancer RNA expression, H3K27 acetylation, and chromatin accessibility. The
repressor function of STAT6 is HDAC3 dependent on a subset of IL-4-repressed
genes. In addition, STAT6-repressed enhancers show extensive overlap with the NF
kappaB p65 cistrome and exhibit decreased responsiveness to lipopolysaccharide
after IL-4 stimulus on a subset of genes. As a consequence, macrophages exhibit
diminished inflammasome activation, decreased IL-1beta production, and
pyroptosis. Thus, the IL-4-STAT6 signaling pathway establishes an alternative
polarization-specific epigenenomic signature resulting in dampened macrophage
responsiveness to inflammatory stimuli.
PMID- 29343446
TI - S-adenosyl methionine prevents ASD like behaviors triggered by early postnatal
valproic acid exposure in very young mice.
AB - INTRODUCTION: A common animal model of ASD is the one induced by valproic acid
(VPA), inducing epigenetic changes and oxidative stress. We studied the possible
preventive effect of the methyl donor for epigenetic enzymatic reactions, S
adenosine methionine (SAM), on ASD like behavioral changes and on redox potential
in the brain and liver in this model. METHODS: ICR albino mice were injected on
postnatal day 4 with one dose of 300 mg/kg of VPA, with normal saline (controls)
or with VPA and SAM that was given orally for 3 days at the dose of 30 mg/kg body
weight. From day 50, we carried out neurobehavioral tests and assessment of the
antioxidant status of the prefrontal cerebral cortex, liver assessing SOD and CAT
activity, lipid peroxidation and the expression of antioxidant genes. RESULTS:
Mice injected with VPA exhibited neurobehavioral deficits typical of ASD that
were more prominent in males. Changes in the activity of SOD and CAT increased
lipid peroxidation and changes in the expression of antioxidant genes were
observed in the prefrontal cortex of VPA treated mice, more prominent in females,
while ASD like behavior was more prominent in males. There were no changes in the
redox potential of the liver. The co-administration of VPA and SAM alleviated
most ASD like neurobehavioral symptoms and normalized the redox potential in the
prefrontal cortex. CONCLUSIONS: Early postnatal VPA administration induces ASD
like behavior that is more severe in males, while the redox status changes are
more severe in females; SAM corrects both. VPA-induced ASD seems to result from
epigenetic changes, while the redox status changes may be secondary.
PMID- 29343444
TI - Activation of p53 in Immature Myeloid Precursor Cells Controls Differentiation
into Ly6c+CD103+ Monocytic Antigen-Presenting Cells in Tumors.
AB - CD103+ dendritic cells are critical for cross-presentation of tumor antigens.
Here we have shown that during immunotherapy, large numbers of cells expressing
CD103 arose in murine tumors via direct differentiation of Ly6c+ monocytic
precursors. These Ly6c+CD103+ cells could derive from bone-marrow monocytic
progenitors (cMoPs) or from peripheral cells present within the myeloid-derived
suppressor cell (MDSC) population. Differentiation was controlled by inflammation
induced activation of the transcription factor p53, which drove upregulation of
Batf3 and acquisition of the Ly6c+CD103+ phenotype. Mice with a targeted deletion
of p53 in myeloid cells selectively lost the Ly6c+CD103+ population and became
unable to respond to multiple forms of immunotherapy and immunogenic
chemotherapy. Conversely, increasing p53 expression using a p53-agonist drug
caused a sustained increase in Ly6c+CD103+ cells in tumors during immunotherapy,
which markedly enhanced the efficacy and duration of response. Thus, p53-driven
differentiation of Ly6c+CD103+ monocytic cells represents a potent and previously
unrecognized target for immunotherapy.
PMID- 29343445
TI - Development, regulation, metabolism and function of bone marrow adipose tissues.
AB - Most adipocytes exist in discrete depots throughout the body, notably in well
defined white and brown adipose tissues. However, adipocytes also reside within
specialized niches, of which the most abundant is within bone marrow. Whereas
bone marrow adipose tissue (BMAT) shares many properties in common with white
adipose tissue, the distinct functions of BMAT are reflected by its development,
regulation, protein secretion, and lipid composition. In addition to its
potential role as a local energy reservoir, BMAT also secretes proteins,
including adiponectin, RANK ligand, dipeptidyl peptidase-4, and stem cell factor,
which contribute to local marrow niche functions and which may also influence
global metabolism. The characteristics of BMAT are also distinct depending on
whether marrow adipocytes are contained within yellow or red marrow, as these can
be thought of as 'constitutive' and 'regulated', respectively. The rBMAT for
instance can be expanded or depleted by myriad factors, including age, nutrition,
endocrine status and pharmaceuticals. Herein we review the site specificity, age
related development, regulation and metabolic characteristics of BMAT under
various metabolic conditions, including the functional interactions with bone and
hematopoietic cells.
PMID- 29343447
TI - Altered B lymphocyte homeostasis and functions in systemic sclerosis.
AB - Beyond the production of autoantibodies, B-cells are thought to play a role in
systemic sclerosis (SSc) by secreting proinflammatory/profibrotic cytokines. B
cells are a heterogeneous population with different subsets distinguished by
their phenotypes and cytokine production. Data about B-cell subsets, cytokine
production and intracellular pathways leading to this production are scarce in
SSc. The aim of our study was to describe B-cell homeostasis, activation,
proliferation, cytokine production in B-cells and serum and B-cell intracellular
signaling pathways in SSc. We hypothezided that B-cell homeostasis and cytokine
production were altered in SSc and could be explained by serum cytokine as well
as by intracellular signaling pathway abnormalities. Forty SSc patients and 20
healthy controls (HC) were prospectively included. B-cell subsets were determined
by flow cytometry using CD19, CD21, CD24, CD38, CD27, IgM and IgD. CD25, CD80,
CD95, HLA-DR were used to assess B-cell activation. Intracellular production of
IL-10 and IL-6 were assessed by flow cytometry after TLR9 and CD40 stimulation.
IL-6, IL-10, Ki67, Bcl2 mRNA were quantified in B-cells. Cytokine production was
also assessed in sera and supernatants of B-cell culture, using a multiplex
approach. Signaling pathways were studied through phosphorylation of mTOR, ERK,
STAT3, STAT5 using a flow cytometry approach. We found that SSc patients
exhibited an altered peripheral blood B-cell subset distribution, with decreased
memory B-cells but increased proportion of naive and CD21LoCD38Lo B-cell subsets.
We observed an increased expression of activation markers (CD80, CD95, HLA-DR) on
some B-cell subsets, mainly the memory B-cells. Secretion of IL-6, BAFF and
CXCL13 were increased in SSc sera. There was no correlation between the
peripheral blood B-cell subsets and the serum concentrations of these cytokines.
After stimulation, we observed a lower proportion of IL-10 and IL-6 producing B
cells in SSc. Finally, we observed a significant decrease of mTOR phosphorylation
in SSc patient B-cells. In conclusion, we observed an altered B-cell homeostasis
in SSc patients compared to HC. Memory B-cells were both decreased and activated
in patients. IL-10 producing B-cells were decreased in SSc. This decrease was
associated with an alteration of mTOR phosphorylation in B-cells. Conversely,
there was no correlation between serum cytokine profile and B-cell homeostasis
alterations.
PMID- 29343449
TI - The comparative efficacy and safety of topical and intravenous tranexamic acid
for reducing perioperative blood loss in Total knee arthroplasty- A randomized
controlled non-inferiority trial.
AB - BACKGROUND: Total Knee Arthroplasty (TKA) can be associated with significant
perioperative blood loss and blood transfusions. This is a prospective randomised
non-inferiority trial comparing intraarticular (IA) and intravenous (IV) routes
of administering Tranexamic acid (TXA) with regard to efficacy and safety.
METHODS: A total of 113 patients who underwent primary unilateral TKA from
January to June 2017 randomly received either 1.5g TXA in 100mL normal saline
solution (IA group, n=58) or 10mg/kg TXA (IV group, n=55) at 10min before the
tourniquet inflation and at tourniquet release. Haemoglobin (Hb) drop on third
day (primary outcome), visible blood loss (VBL), hidden blood loss (HBL), total
blood loss (TBL), transfusion requirement, incidence of deep vein thrombosis
(DVT), wound complications and renal function derangement (secondary outcomes)
were recorded. RESULTS: The mean difference in haemoglobin drop between both
groups was 0.25g/dL with 90% CI of -0.07 to 0.58. Since the lower bound of 90% CI
was above equivalence margin of -0.35, IA group was found to be non-inferior to
IV group in terms of Hb drop. The mean difference between both groups of VBL, HBL
and TBL were 0.85mL (p value 0.90), -7.9mL (p value 0.90) and -6.2mL (p value
0.93) respectively. Transfusions and wound complications were statistically
insignificant. None of the patients had DVT or renal function derangement.
CONCLUSION: IA TXA is not inferior to IV TXA with regard to efficacy and safety
and may be preferred considering ease of administration and lack of systemic
absorption.
PMID- 29343448
TI - Optimizing the dose of local infiltration analgesia and gabapentin for total knee
arthroplasty, a randomized single blind trial in 128 patients.
AB - BACKGROUND AND PURPOSE: Effective analgesia is essential for postoperative
recovery and rehabilitation in TKA. The challenge of analgesic regimes is to
obtain adequate pain relief and maximum muscle control to mobilize and
rehabilitate patients early. However, the optimal dose and best composition are
not known. We hypothesized that there would be no differences in reported
postoperative pain on the day of the TKA surgery as well as the first day after
surgery when different combinations of ropivacain for LIA and gabapentin are
given. METHODS: This prospective randomized trial examined 128 TKA patients
treated with LIA and gabapentin in four groups. Group A: 300-mg ropivacain/600
300-300-mg gabapentin. Group B: 150-mg ropivacain/600-300-300-mg gabapentin.
Group C: 300-mg ropivacain/300-100-100-mg gabapentin. Group D: 150-mg
ropivacain/300-100-100-mg gabapentin. Primary endpoint was pain (NRS) at multiple
moments. Secondary endpoints were number of adverse effects, length of hospital
stay (LOS), the amount of consumption of pain medication, and wound leakage.
Generalized estimating equation (GEE) was used to detect differences between the
four groups regarding the course of pain. RESULTS: No differences regarding
adverse effects, LOS, and wound leakage were found. GEE revealed a significant
difference in course of pain between group A and B, with group B experiencing
higher NRS scores postoperatively than group A (p=0.021). No differences between
the other groups were found. INTERPRETATION: The results of the current study
suggest that LIA with 300-mg (150ml) ropivacain might be more effective than 150
mg (75ml) ropivacain. Alteration in dose of gabapentin appears not to have
influence on the course of pain.
PMID- 29343450
TI - Paediatric physeal sparing posterior cruciate ligament (PCL) reconstruction with
parental donation allograft: Rationale and operative approach.
AB - BACKGROUND: Paediatric PCL injuries are rare but constitute a significant
management challenge. We describe a novel approach to the surgical management of
an 11-year-old boy who presented with persisting symptomatic instability
following 18months of failed conservative therapy. METHODS: PCL reconstruction
was performed using a physeal sparing, all-inside technique under fluoroscopic
control. This avoids the potential for iatrogenic growth injury. A parentally
donated hamstrings allograft was used to ensure adequate graft size, and
reinforced using a non-elastic two millimetre braided suture. Graft reinforcement
safeguards against stretching during the early healing phase, but must be removed
thereafter to avoid creating a physeal tether. RESULTS: At three months, clinical
examination under anaesthesia showed equivalent PCL laxity in the operated knee
compared to the normal contralateral knee. The graft reinforcement tape was
incised as planned with no change in laxity assessment. Arthroscopic evaluation
demonstrated a quiet joint with a well healed graft and no synovitis.
Postoperative long leg radiographs showed no growth deformity against
preoperative status. CONCLUSION: In paediatric patients with persisting
symptomatic instability despite appropriate conservative management, surgical
reconstruction of the PCL should be considered. Standard treatment has higher
complication rates and poorer graft survival than in an adult cohort. Specific
problems include iatrogenic growth plate injury causing growth arrest or angular
deformity, inadequate graft size if using hamstrings autograft, and the
additional technical challenge of small patient size. Early results from extra
physeal, all-inside PCL reconstruction using a parentally donated allograft are
promising and may provide an alternative solution to traditional surgical
management.
PMID- 29343451
TI - Biochemical characterization of halophilic, alkalithermophilic amylopullulanase
PulD7 and truncated amylopullulanases PulD7DeltaN and PulD7DeltaC.
AB - A pullulanase, PulD7, was identified in the genome of the halophilic,
alkalithermophilic isolate Alkalilimnicola sp. NM-DCM-1. PulD7 is 701 amino acids
large with a carbohydrate binding module (CBM) 48 at the N-terminal. The full
length PulD7 and N- and C-terminal truncated versions were cloned, heterologously
expressed and functionally characterized. PulD7 displayed maximal activity at 55
degrees C, pH 9.5 and 2 M NaCl. PulD7 had good thermal stability, with a half
life of 693 min at 50 degrees C. PulD7 is an amylopullulanase, hydrolyzing both
alpha-1,4- and alpha-1,6-glycosidic bonds in soluble starch and pullulan,
respectively. PulD7 was resistant to chemical reagents, including organic
solvents (dimethyl sulfoxide, methanol, benzene, 20% v/v), reducing agents (beta
mercaptoethanol, 5% v/v), surfactants (SDS and Tween 20, 5% v/v), the divalent
chelator ethylene diamine tetra acetic acid (5 mM), and the chemical denaturant
urea (8 M). PulD7 was not calcium-dependent. PulD7 was able to bind raw starch
granules, reaching 52% binding in 3 h. The N-and C-terminal truncated forms of
PulD7 had similar biochemical characteristics. PulD7DeltaC had higher specific
activity and halotolerance. The N-terminally truncated PulD7DeltaN hydrolyzed
amylose only, indicating that CBM48 is essential for binding branched substrates.
PulD7 has unique characteristics giving it strong potential for application in
biotechnological industries.
PMID- 29343452
TI - A cell-penetrating peptide conjugated carboxymethyl-beta-cyclodextrin to improve
intestinal absorption of insulin.
AB - In this study, a cell-penetrating peptide conjugate, R8-carboxymethyl-beta
cyclodextrin (R8-CM-beta-CD), was synthesized, and then we prepared the
supramolecular complex (insulin/R8-CM-beta-CD). The physicochemical properties of
the complex were characterized. The supramolecular complex could facilitate the
uptake of insulin, meanwhile, induce a significantly higher internalization of
insulin. Interestingly, the transportation efficiency of insulin/R8-CM-beta-CD
across the Caco-2 cell monolayer was about 3 times greater than that of
insulin/CM-beta-CD. Further studies on the mechanism in increasing uptake
efficiency showed that R8-CM-beta-CD was internalized via different styles of
endocytosis and could inhibit P-glycoprotein (P-gp) efflux pumps. Importantly,
the formulation of insulin/R8-CM-beta-CD showed the highest increase in the
permeability of insulin and the best biological response in diabetic rats of all
the treatments. In addition, no sign of toxicity was observed after
administrations of R8-CM-beta-CD. These results demonstrated that R8-CM-beta-CD
was a promising carrier for use in protein drug delivery.
PMID- 29343453
TI - Polygonatum sibiricum polysaccharides play anti-cancer effect through TLR4
MAPK/NF-kappaB signaling pathways.
AB - OBJECTIVE: To investigate the anti-cancer effect of Polygonatum sibiricum
polysaccharides (PSP) and the underlying mechanism. METHODS: Tumor-bearing mice
were randomly divided into normal saline (NS) group, adriamycin (ADM) group, PSP
group and lipopolysaccharide (LPS) group. RAW264.7 cells were pre-treated with or
without TLR4 inhibitor or MyD88 inhibitor. Quantitative RT-PCR and Western blot
were performed to detect the mRNA and protein expressions, respectively. ELISA
and Griess reaction was used to measure cytokines and NO levels. Flow cytometry
was employed to examine T-lymphocyte subset and CCK-8 assay was used for cell
viability. RESULTS: The in vivo experiment found that PSP inhibited tumor growth
and improved the spleen index, thymus index, the cytokines secretion and
CD4+/CD8+ lymphocytes ratio. Compared with the NS group, the mRNA and protein
expressions of the critical nodes inTLR4-MAPK/NF-kappaB signaling pathways
(except TRAM) significantly increased in PSP group, as well as the NO and
cytokines levels. Nevertheless, PSP had no obvious effects on TRAM. Further
analysis showed that PSP effects on the critical nodes in TLR4-MAPK/NF-kappaB
signaling pathways were suppressed by inhibitor in vitro. CONCLUSION: The
immunoenhancement effect of PSP against lung cancer is mediated by TLR4-MAPK/NF
kappaB signaling pathways.
PMID- 29343454
TI - Rational design and evaluation of HBsAg polymeric nanoparticles as antigen
delivery carriers.
AB - The present work is focused on the development and evaluation of single dose
sustained-release Hepatitis B surface antigen (HBsAg) loaded nanovaccine for
Hepatitis B. The conventional treatment suffers from repeated administration and
hence requires a booster dose. Therefore, polymeric nanovaccine of HBsAg was
developed by double emulsion solvent evaporation technique, utilizing central
composite design for formulation optimization. The effects of independent
variables (like polymer amount, stabilizer concentration, aqueous/organic phase
ratio and homogenizer speed) were also studied on critical quality attributes
like particle size and entrapment efficiency. Nanovaccine was characterized in
terms of physicochemical parameters, release, internalization and in vivo
immunological evaluation in BALB/c mice after administration by different routes
such as oral, sub-cutaneous, nasal and intramuscular. The designed nanovaccine
demonstrated nanometric size with smooth surface, negative zeta potential,
maximum entrapment, sustained release and better internalization in macrophage
and MRC-5 cell line. The immune-stimulating activity of nanovaccine administered
by different routes was evaluated by measuring anti-HBsAg titre like specific
immunoglobulin IgG and IgA response and cytokine level (interleukin-2, interferon
Y) measurement. The results indicated that the nanovaccine administered by
intramuscular route produced better humoral as well as cellular responses and
potential carriers for antigen delivery at single dose administration via
intramuscular route.
PMID- 29343456
TI - EEG Dynamics and Neural Generators in Implicit Navigational Image Processing in
Adults with ADHD.
AB - In contrast to childhood ADHD that is characterized by inattention, impulsivity
and hyperactivity, most adults with ADHD predominantly exhibit inattention. We
used a new oddball paradigm using implicit navigational images and analyzed EEG
dynamics with swLORETA inverse modeling of the evoked potential generators to
study cortical processing in adults with ADHD and age-matched controls. In
passive observation, we demonstrated that P350 amplitude, alpha-beta oscillation
event-related synchronization (ERS) anticipation, and beta event-related
desynchronization (ERD) were significantly smaller in ADHD. In the active
condition, P100 duration was reduced and N140 amplitude increased for both
deviant and frequent conditions in the ADHD. Alpha ERS and delta-theta ERS were
reduced in the ADHD in the deviant condition. The left somatosensory area (BA2)
and the right parietal lobe (BA31, BA40) contributed more to the P100 generators
in the control than in the ADHD group, while the left frontal lobe (BA10)
contributed more to the P100 generators in the ADHD. The left inferior parietal
lobe (BA40) contributed more to the N140 generators in the control than the ADHD
group while the right posterior cingulate (BA30) contributed more to the N140
generators in the ADHD. These findings reinforce the notion that earlier cortical
stages of visual processing are compromised in adult ADHD by inducing the
emergence of different even-related potential generators and EEG dynamics in
ADHD. Considering that classical approaches for ADHD diagnosis are based on
qualitative clinical investigation possibly biased by subjectivity, EEG analysis
is another objective tool that might contribute to diagnosis, future
neurofeedback or brain stimulation therapies.
PMID- 29343457
TI - Sphingolipid signaling in renal fibrosis.
AB - Over the last decade, various sphingolipid subspecies have gained increasing
attention as important signaling molecules that regulate a multitude of
physiological and pathophysiological processes including inflammation and tissue
remodeling. These mediators include ceramide, sphingosine 1-phosphate (S1P), the
cerebroside glucosylceramide, lactosylceramide, and the gangliosides GM3 and Gb3.
These lipids have been shown to accumulate in various chronic kidney diseases
that typically end in renal fibrosis and ultimately renal failure. This review
will summarize the effects and contributions of those enzymes that regulate the
generation and interconversion of these lipids, notably the acid
sphingomyelinase, the acid sphingomyelinase-like protein SMPDL3B, the sphingosine
kinases, the S1P lyase, the glucosylceramide synthase, the GM3 synthase, and the
alpha-galactosidase A, to renal fibrotic diseases. Strategies of manipulating
these enzymes for therapeutic purposes and the impact of existing drugs on renal
pathologies will be discussed.
PMID- 29343455
TI - Adolescent Social Stress Increases Anxiety-like Behavior and Alters Synaptic
Transmission, Without Influencing Nicotine Responses, in a Sex-Dependent Manner.
AB - Early-life stress is a risk factor for comorbid anxiety and nicotine use. Because
little is known about the factors underlying this comorbidity, we investigated
the effects of adolescent stress on anxiety-like behavior and nicotine responses
within individual animals. Adolescent male and female C57BL/6J mice were exposed
to chronic variable social stress (CVSS; repeated cycles of social isolation +
social reorganization) or control conditions from postnatal days (PND) 25-59.
Anxiety-like behavior and social avoidance were measured in the elevated plus
maze (PND 61-65) and social approach-avoidance test (Experiment 1: PND 140-144;
Experiment 2: 95-97), respectively. Acute nicotine-induced locomotor,
hypothermic, corticosterone responses, (Experiment 1: PND 56-59; Experiment 2:
PND 65-70) and voluntary oral nicotine consumption (Experiment 1: PND 116-135;
Experiment 2: 73-92) were also examined. Finally, we assessed prefrontal cortex
(PFC) and nucleus accumbens (NAC) synaptic transmission (PND 64-80); brain
regions that are implicated in anxiety and addiction. Mice exposed to adolescent
CVSS displayed increased anxiety-like behavior relative to controls. Further,
CVSS altered synaptic excitability in PFC and NAC neurons in a sex-specific
manner. For males, CVSS decreased the amplitude and frequency of spontaneous
excitatory postsynaptic currents in the PFC and NAC, respectively. In females,
CVSS decreased the amplitude of spontaneous inhibitory postsynaptic currents in
the NAC. Adolescent CVSS did not affect social avoidance or nicotine responses
and anxiety-like behavior was not reliably associated with nicotine responses
within individual animals. Taken together, complex interactions between PFC and
NAC function may contribute to adolescent stress-induced anxiety-like behavior
without influencing nicotine responses.
PMID- 29343458
TI - Right ventricular fibrosis and dysfunction: Actual concepts and common
misconceptions.
AB - Fibrosis and remodeling of the right ventricle (RV) are associated with RV
dysfunction and mortality of patients with pulmonary hypertension (PH) but it is
unknown how much RV fibrosis contributes to RV dysfunction and mortality. RV
fibrosis manifests as fibroblast accumulation and collagen deposition which may
be excessive. Although extracellular matrix deposition leads to elevated
ventricular stiffness, it is not known to which extent it affects RV function.
Various animal models of pulmonary hypertension have been established to
investigate the role of fibrosis in RV dysfunction and failure. However, they do
not perfectly resemble the human disease. In the current review we describe the
major characteristics of RV fibrosis, molecular mechanisms regulating the
fibrotic process, and discuss how therapeutic targeting of fibrosis might affect
RV function.
PMID- 29343459
TI - Differing structural properties of foods affect the development of mandibular
control and muscle coordination in infants and young children.
AB - The development of chewing is an essential motor skill that is continually
refined throughout early childhood. From a motor control perspective, the
advancement of textures is dependent upon the fit between a child's oral anatomic
and motor system and food properties. The purpose of this exploratory study is to
identify age-related changes in chewing motor coordination and control and to
determine if these changes are associated with the differing structural
properties of solid foods, as well as to explore the role of explanatory
variables such as the emergence of teeth and bite force. The masticatory muscle
coordination (i.e., coupling of synergistic and antagonistic muscle pairs) and
control (i.e., speed, displacement, chewing rate, duration, and number of chews)
of fifty children were assessed cross-sectionally at five ages: 9-, 12-, 18-, 24
, and 36-months using electromyography (EMG) and 3D optical motion capture while
children ate three foods that had differing structural properties. The results of
this study found that children made gains in their chewing motor control
(decreased duration of chewing sequences and lateral jaw displacement) and
coordination (improved jaw muscle coupling) throughout this period. The
structural differences in foods also affected chewing performance at all ages.
These preliminary findings suggest that some solid textures are better adapted
for immature mandibular control than others and that the development of chewing
is a protracted process that may be impacted by the emergence of teeth and
changes to bite force.
PMID- 29343460
TI - Facebook Groups for the Management of Chronic Diseases.
AB - The use of Facebook groups by health care researchers and professionals for
chronic disease management, namely type 2 diabetes mellitus and coronary heart
disease, is in its early stages and challenges are emerging. While Facebook
groups offer great potential to deliver health support, research of Facebook
groups for chronic disease management remains in its infancy, with robust
evidence not yet available. Designing Facebook groups that are acceptable to
users, health care researchers as well as health care professionals is a
challenge, and there is a poor fit with traditional research and evaluation
methods. Key recommendations for future research of Facebook groups for chronic
disease management include: (1) iterative content development with input from the
target patient population; (2) further understanding of the potential role of
group "champions"; (3) ensuring the social media policies of health care
institutions allow for real time online communication; and (4) utilizing
comprehensive evaluation strategies, including the use of process evaluations.
PMID- 29343462
TI - A Tailored Web-based Advice Tool for Skiers and Snowboarders: Protocol for a
Randomized Controlled Trial.
AB - BACKGROUND: Being active in sports has many positive health effects. The direct
effects of engaging in regular physical activity are particularly apparent in the
prevention of several chronic diseases, including cardiovascular disease,
diabetes, cancer, hypertension, obesity, depression, and osteoporosis. Besides
the beneficial health effects of being active, sports participation is
unfortunately also associated with a risk of injuries. In the case of many sports
injuries (eg, winter sports) preventive measures are not compulsory, which means
that a behavioral change in sports participants is necessary to increase the use
of effective measures, and subsequently prevent or reduce injuries in sports.
OBJECTIVE: The evidence-based Wintersportklaar online intervention has been
developed to stimulate injury preventive behavior among skiers and snowboarders.
In this article, the design of the effectiveness study will be described.
METHODS: A randomized controlled trial with a follow-up period of four months
during the winter sport season will be conducted. The participants consist of
inexperienced skiers and snowboarders. At baseline, skiers and snowboarders in
the intervention and control groups are asked to report the injury preventive
measures they usually take during their preparation for their winter sport
holiday. One and three months after baseline, skiers and snowboarders are asked
to report retrospectively in detail what measures they took regarding injury
prevention during their current winter sport preparation and winter sport
holiday. Descriptive analyses (mean, standard deviation, frequency, range) are
conducted for the different baseline variables in both study groups. To evaluate
the success of the randomization, baseline values are analyzed for differences
between the intervention and control groups (chi square, independent T tests
and/or Mann-Whitney test). Chi square tests and/or logistic regression analyses
are used to analyze behavioral change according to the intention to treat
principle (as initially assigned). RESULTS: The project was funded in 2016 and
enrolment was completed in 2017. Data analysis is currently under way and the
first results are expected to be submitted for publication in 2018. CONCLUSIONS:
To combat the negative side effects of sports participation, the use of injury
preventive measures is desirable. As the use of injury prevention is usually not
compulsory in skiing and snowboarding, a behavioral change is necessary to
increase the use of effective injury preventive measures in winter sports. TRIAL
REGISTRATION: Dutch Trial Registry NTR6233;
http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6233 (Archived by
WebCite at http://www.webcitation.org/6wXZPzjUi).
PMID- 29343461
TI - Effects of Psychiatric Comorbidity in Immune-Mediated Inflammatory Disease:
Protocol for a Prospective Study.
AB - BACKGROUND: Immune-mediated inflammatory diseases (IMID), such as inflammatory
bowel disease (IBD), multiple sclerosis (MS), and rheumatoid arthritis (RA), are
highly prevalent in Canada and the United States and result in substantial
personal and societal burden. The prevalence of psychiatric comorbidities,
primarily depression and anxiety, in IMID exceeds those in the general population
by two- to threefold, but remains underdiagnosed and undertreated. Furthermore,
the effects of psychiatric comorbidity on IMID are not well understood.
OBJECTIVE: The objectives of this study were (1) to compare health-related
quality of life and work ability in persons with IMID and psychiatric comorbidity
with those of persons with IMID without psychiatric comorbidity and with those of
persons with depression and anxiety disorders alone, and (2) to validate existing
case identification tools for depression and anxiety in persons with IMID to
facilitate improved identification of depression and anxiety by clinicians. To
achieve these objectives, we designed a prospective 3-year longitudinal study. In
this paper, we aim to describe the study rationale and design and the
characteristics of study participants. METHODS: Between November 2014 and July
2016, we recruited 982 individuals from multiple clinic and community sources; 18
were withdrawn due to protocol violations. RESULTS: The final study sample
included 247 participants with IBD, 255 with MS, 154 with RA, and 308 with
depression or anxiety. The majority were white, with the proportion ranging from
85.4% (IBD [210/246]; MS [217/254]) to 74.5% (114/153, RA; P=.01). There was a
female predominance in all groups, which was highest in the RA cohort (84.4%,
130/154) and least marked in the IBD cohort (62.7%, 155/247). Participants with
depression or anxiety were more likely to be single (36.0%, 111/308) than
participants in any other group (11.8% [30/255]-22.7% [56/247], P<.001).
CONCLUSIONS: This paper presents the rationale for this study, describes study
procedures, and characterizes the cohort enrolled. Ultimately, the aim is
improved care for individuals affected by IMID.
PMID- 29343463
TI - The Impact of mHealth Interventions: Systematic Review of Systematic Reviews.
AB - BACKGROUND: Mobile phone usage has been rapidly increasing worldwide. mHealth
could efficiently deliver high-quality health care, but the evidence supporting
its current effectiveness is still mixed. OBJECTIVE: We performed a systematic
review of systematic reviews to assess the impact or effectiveness of mobile
health (mHealth) interventions in different health conditions and in the
processes of health care service delivery. METHODS: We used a common search
strategy of five major scientific databases, restricting the search by
publication date, language, and parameters in methodology and content.
Methodological quality was evaluated using the Measurement Tool to Assess
Systematic Reviews (AMSTAR) checklist. RESULTS: The searches resulted in a total
of 10,689 articles. Of these, 23 systematic reviews (371 studies; more than
79,665 patients) were included. Seventeen reviews included studies performed in
low- and middle-income countries. The studies used diverse mHealth interventions,
most frequently text messaging (short message service, SMS) applied to different
purposes (reminder, alert, education, motivation, prevention). Ten reviews were
rated as low quality (AMSTAR score 0-4), seven were rated as moderate quality
(AMSTAR score 5-8), and six were categorized as high quality (AMSTAR score 9-11).
A beneficial impact of mHealth was observed in chronic disease management,
showing improvement in symptoms and peak flow variability in asthma patients,
reducing hospitalizations and improving forced expiratory volume in 1 second;
improving chronic pulmonary diseases symptoms; improving heart failure symptoms,
reducing deaths and hospitalization; improving glycemic control in diabetes
patients; improving blood pressure in hypertensive patients; and reducing weight
in overweight and obese patients. Studies also showed a positive impact of SMS
reminders in improving attendance rates, with a similar impact to phone call
reminders at reduced cost, and improved adherence to tuberculosis and human
immunodeficiency virus therapy in some scenarios, with evidence of decrease of
viral load. CONCLUSIONS: Although mHealth is growing in popularity, the evidence
for efficacy is still limited. In general, the methodological quality of the
studies included in the systematic reviews is low. For some fields, its impact is
not evident, the results are mixed, or no long-term studies exist. Exceptions
include the moderate quality evidence of improvement in asthma patients,
attendance rates, and increased smoking abstinence rates. Most studies were
performed in high-income countries, implying that mHealth is still at an early
stage of development in low-income countries.
PMID- 29343464
TI - Cardiorespiratory Fitness, Coronary Artery Calcium, and Cardiovascular Disease
Events in a Cohort of Generally Healthy Middle-Age Men: Results From the Cooper
Center Longitudinal Study.
AB - BACKGROUND: A robust literature demonstrates that coronary artery calcification
(CAC) and cardiorespiratory fitness (CRF) are independent predictors of
cardiovascular disease (CVD) events. Much less is known about the joint
associations of CRF and CAC with CVD risk. In the setting of high CAC, high
versus low CRF has been associated with decreased CVD events. The goal of this
study was to assess the effect of continuous levels of CRF on CVD risk in the
setting of increasing CAC burden. METHODS: We studied 8425 men without clinical
CVD who underwent preventive medicine examinations that included an objective
measurement of CRF and CAC between 1998 and 2007. There were 383 CVD events
during an average follow-up of 8.4 years. Parametric proportional hazards
regression models based on a Gompertz mortality rule were used to estimate total
CVD incidence rates at 70 years of age as well as hazard ratios for the included
covariates. RESULTS: CVD events increased with increasing CAC and decreased with
increasing CRF. Adjusting for CAC level (scores of 0, 1-99, 100-399, and >=400),
for each additional MET of fitness, there was an 11% lower risk for CVD events
(hazard ratio, 0.89; 95% confidence interval, 0.84-0.94). When CAC and CRF were
considered together, there was a strong association between continuous CRF and
CVD incidence rates in all CAC groups. CONCLUSIONS: In a large cohort of
generally healthy men, there is an attenuation of CVD risk at all CAC levels with
higher CRF.
PMID- 29343466
TI - Long-term cardiovascular prognosis after transient ischemic attack: Associated
predictors.
AB - OBJECTIVE: To determine long-term cardiovascular risk after TIA and to identify
the factors associated with increased risk. METHODS: This was a prospective
observational registry of TIA patients admitted to the emergency room of our
tertiary stroke center from June 2006 to January 2016. New vascular events (NVEs)
were recorded from 3 months after TIA onset until June 2017, including both
stroke and nonstroke events (coronary and peripheral disease). We registered TIA
etiology, age, sex, vascular risk factors, radiologic data, and clinical TIA
features and analyzed these variables in relation to NVE long-term risk. RESULTS:
In total, 676 patients 71.7 +/- 13.7 years of age were included, with a mean
follow-up of 48.8 +/- 32.7 months. An NVE was detected in 173 patients (25.6%)
without significant differences between event types (p = 0.84). Univariate
analysis associated NVEs with etiologic subgroup, male sex, diabetes mellitus,
hypertension, previous vascular disease, duration and clinical features of TIA,
and signs of acute infarction. Multivariable analysis showed an independent
association of NVEs with etiologic TIA subgroup, signs of acute infarction, and
duration of TIA symptoms. Large artery atherosclerosis and cardioaortic embolism
had the highest NVE risk, with a slightly higher percentage of nonstroke events.
The small artery disease subgroup had the lowest NVE risk, with a higher
percentage of stroke events. CONCLUSIONS: Etiology subgroup was the main factor
determining high long-term risk of vascular events in patients with TIA. Large
artery atherosclerosis carried the highest vascular risk, both nonstroke and
stroke, followed by cardioaortic embolism.
PMID- 29343465
TI - Sex differences in cerebrovascular pathologies on FLAIR in cognitively unimpaired
elderly.
AB - OBJECTIVE: To examine sex differences in cerebrovascular pathologies (CVPs) as
seen on fluid-attenuated inversion recovery (FLAIR) MRI and in cardiovascular and
metabolic risk factors in a population-based cognitively unimpaired cohort and to
examine whether sex is independently associated with FLAIR findings after
accounting for differences in important midlife risk factors. METHODS: We
identified 1,301 cognitively normal participants (663 men and 638 women) enrolled
in the Mayo Clinic Study of Aging (age >=70 years) who had FLAIR MRI and
ascertained total burden of white matter (WM) hyperintensities (WMH), subcortical
infarctions, and cortical infarctions. We compared CVPs and midlife and late-life
vascular risk factors between men and women. We fit regression models with each
CVP as an outcome, treating age, sex, and midlife risk factors as predictors.
RESULTS: Women had significantly greater WMH volume relative to their WM volume
compared to men (2.8% vs 2.4% of WM, p < 0.001), while men had a greater
frequency of cortical infarctions compared to women (9% vs 4%, p < 0.001).
Subcortical infarctions were equally common in men and women (20%). In regression
modeling after adjustment for WM volume, the mean WMH volume difference between
men and women was of the same magnitude as a 7-year difference in age. In
contrast, men had 2.2-greater relative odds of having a cortical infarction
compared to women. These sex differences persisted even after adjustment for
midlife vascular risk factors. CONCLUSIONS: There were important sex differences
in CVP findings on FLAIR in cognitively unimpaired elderly. Understanding these
sex differences could aid in the development of sex-specific preventive
strategies.
PMID- 29343467
TI - Hearing impairment in patients with myotonic dystrophy type 2.
AB - OBJECTIVE: To systematically assess auditory characteristics of a large cohort of
patients with genetically confirmed myotonic dystrophy type 2 (DM2). METHODS:
Patients with DM2 were included prospectively in an international cross-sectional
study. A structured interview about hearing symptoms was held. Thereafter,
standardized otologic examination, pure tone audiometry (PTA; 0.25, 0.5, 1, 2, 4,
and 8 kHz), speech audiometry, tympanometry, acoustic middle ear muscle reflexes,
and brainstem auditory evoked potentials (BAEP) were performed. The ISO 7029
standard was used to compare the PTA results with established hearing thresholds
of the general population according to sex and age. RESULTS: Thirty-one Dutch and
25 French patients with DM2 (61% female) were included with a mean age of 57
years (range 31-78). The median hearing threshold of the DM2 cohort was higher
for all measured frequencies, compared to the 50th percentile of normal (p <
0.001). Hearing impairment was mild in 39%, moderate in 21%, and severe in 2% of
patients with DM2. The absence of an air-bone gap with PTA, concordant results of
speech audiometry with PTA, and normal findings of BAEP suggest that the
sensorineural hearing impairment is located in the cochlea. A significant
correlation was found between hearing impairment and age, even when corrected for
presbycusis. CONCLUSIONS: Cochlear sensorineural hearing impairment is a frequent
symptom in patients with DM2, suggesting an early presbycusis. Therefore, we
recommend informing about hearing impairment and readily performing audiometry
when hearing impairment is suspected in order to propose early hearing
rehabilitation with hearing aids when indicated.
PMID- 29343468
TI - Onabotulinum toxin-A injections for sleep bruxism: A double-blind, placebo
controlled study.
AB - OBJECTIVES: To test the safety and efficacy of onabotulinum toxin-A (BoNT-A)
injections into the masseter and temporalis muscles in patients with symptomatic
sleep bruxism. METHODS: Participants 18 to 85 years old with clinically diagnosed
sleep bruxism confirmed by polysomnography were enrolled in this randomized,
placebo-controlled, 1:1, parallel-design trial with open-label extension.
Participants were injected with BoNT-A 200 units (60 into each masseter and 40
into each temporalis) or placebo and were evaluated at 4 to 8 weeks after the
initial treatment visit. The primary efficacy endpoint was clinical global
impression (CGI), and the secondary efficacy endpoint was a visual analog scale
(VAS) of change in bruxism and in pain at 4 to 8 weeks after injection.
Exploratory endpoints included modified Montreal Bruxism Questionnaire, Headache
Impact Test-6, total Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale,
Self-Rated Anxiety Scale, and polysomnography data, including EMG recordings of
the masseter and temporalis muscle bruxing events. Adverse events were recorded.
RESULTS: Thirty-one participants were recruited and 23 were randomized (19
female, age 47.4 +/- 16.9 years). All 13 randomized to BoNT-A and 9 of 10
randomized to placebo completed the study. CGI (p < 0.05) and VAS of change (p <
0.05) favored the BoNT-A group. None of the exploratory endpoints changed
significantly, but total sleep time and number/duration of bruxing episodes
favored the BoNT-A group. Two participants randomized to BoNT-A reported a
cosmetic change in their smile. No dysphagia or masticatory adverse events were
reported. CONCLUSIONS: BoNT-A effectively and safely improved sleep bruxism in
this placebo-controlled pilot trial. A large multicenter trial is needed to
confirm these encouraging data. CLINICALTRIALSGOV IDENTIFIER: NTC00908050. CLASS
OF EVIDENCE: This study provides Class II evidence that botulinum injections into
the masseter and temporalis muscles improve subjective bruxism and painful
symptoms associated with sleep bruxism.
PMID- 29343469
TI - Entrustable professional activities: A useful concept for neurology education.
AB - Medical education is currently undergoing a paradigm shift from process-based to
competency-based education, focused on measuring the desired competence of a
physician. In an attempt to improve the assessment framework used for medical
education, the concept of entrustable professional activities (EPAs) has gained
traction. EPAs are defined as professional activities that can be entrusted to an
individual in a clinical context. The Association of American Medical Colleges
(AAMC) defined a set of 13 such EPAs to define the core of what all students
should be able to do on day 1 of residency, regardless of specialty choice. The
AAMC is currently piloting these EPAs with 10 medical schools to determine if
EPAs can be used as a way to observe, measure, and entrust medical students with
core clinical activities by the end of the clinical immersion experiences of the
third year. The specialty of pediatrics is piloting the use of specialty-specific
EPAs at 5 medical schools to assess readiness for transitions from medical school
into pediatric residency training and practice. To date, no neurology-specific
EPAs have been published for use in neurology clerkships or neurology
residencies. This article introduces the concept of EPAs in the context of
competency-based medical education and describes how EPAs might be relevant and
applicable in neurologic education across the continuum. The Undergraduate
Education Subcommittee of the American Academy of Neurology advocates for a
proactive approach to incorporating core EPAs in undergraduate medical education
and to considering an EPA-based specialty-specific assessment framework for
neurology.
PMID- 29343471
TI - Infantile-onset hand dystonia with intellectual disability: Clues to ARX
mutations.
PMID- 29343470
TI - Cognition in multiple sclerosis: State of the field and priorities for the
future.
AB - Cognitive decline is recognized as a prevalent and debilitating symptom of
multiple sclerosis (MS), especially deficits in episodic memory and processing
speed. The field aims to (1) incorporate cognitive assessment into standard
clinical care and clinical trials, (2) utilize state-of-the-art neuroimaging to
more thoroughly understand neural bases of cognitive deficits, and (3) develop
effective, evidence-based, clinically feasible interventions to prevent or treat
cognitive dysfunction, which are lacking. There are obstacles to these goals. Our
group of MS researchers and clinicians with varied expertise took stock of the
current state of the field, and we identify several important practical and
theoretical challenges, including key knowledge gaps and methodologic limitations
related to (1) understanding and measurement of cognitive deficits, (2)
neuroimaging of neural bases and correlates of deficits, and (3) development of
effective treatments. This is not a comprehensive review of the extensive
literature, but instead a statement of guidelines and priorities for the field.
For instance, we provide recommendations for improving the scientific basis and
methodologic rigor for cognitive rehabilitation research. Toward this end, we
call for multidisciplinary collaborations toward development of biologically
based theoretical models of cognition capable of empirical validation and
evidence-based refinement, providing the scientific context for effective
treatment discovery.
PMID- 29343472
TI - Clinical spectrum of hemiplegic migraine and chances of finding a pathogenic
mutation.
AB - OBJECTIVE: To investigate whether the clinical characteristics of patients with
hemiplegic migraine with and without autosomal dominant mutations in CACNA1A,
ATP1A2, or SCN1A differ, and whether the disease may be caused by mutations in
other genes. METHODS: We compared the clinical characteristics of 208 patients
with familial (n = 199) or sporadic (n = 9) hemiplegic migraine due to a mutation
in CACNA1A, ATP1A2, or SCN1A with those of 73 patients with familial (n = 49) or
sporadic (n = 24) hemiplegic migraine without a mutation in these genes. In
addition, 47 patients (familial: n = 33; sporadic: n = 14) without mutations in
CACNA1A, ATP1A2, or SCN1A were scanned for mutations in novel genes using whole
exome sequencing. RESULTS: Patients with mutations in CACNA1A, ATP1A2, or SCN1A
had a lower age at disease onset, larger numbers of affected family members, and
more often attacks (1) triggered by mild head trauma, (2) with extensive motor
weakness, and (3) with brainstem features, confusion, and brain edema. Mental
retardation and progressive ataxia were exclusively found in patients with a
mutation. Whole exome sequencing failed to identify pathogenic mutations in new
genes. CONCLUSIONS: Most patients with hemiplegic migraine without a mutation in
CACNA1A, ATP1A2, or SCN1A display a mild phenotype that is more akin to that of
common (nonhemiplegic) migraine. A major fourth autosomal dominant gene for
hemiplegic migraine remains to be identified. Our observations might guide
physicians in selecting patients for mutation screening and in providing adequate
genetic counseling.
PMID- 29343473
TI - Smoking affects the interferon beta treatment response in multiple sclerosis.
AB - OBJECTIVE: To investigate whether smoking in patients with relapsing-remitting
multiple sclerosis (RRMS) treated with interferon beta (IFN-beta) is associated
with the relapse rate and whether there is an interaction between smoking and
human leukocyte antigen (HLA)-DRB1*15:01, HLA-A*02:01, and the N
acetyltransferase-1 (NAT1) variant rs7388368A. METHODS: DNA from 834 IFN-beta
treated patients with RRMS from the Danish Multiple Sclerosis Biobank was
extracted for genotyping. Information about relapses from 2 years before the
start of treatment to either the end of treatment or the last follow-up visit was
obtained from the Danish Multiple Sclerosis Treatment Register. Smoking
information came from a comprehensive questionnaire. RESULTS: We found that the
relapse rate in patients with RRMS during IFN-beta treatment was higher in
smokers compared to nonsmokers, with an incidence rate ratio (IRR) of 1.20 (95%
confidence interval [CI] 1.021-1.416, p = 0.027) and with an IRR increase of 27%
per pack of cigarettes per day (IRR 1.27, 95% CI 1.056-1.537, p = 0.012). We
found no association or interaction with HLA and the NAT1 variant. CONCLUSION: In
this observational cohort study, we found that smoking is associated with
increased relapse activity in patients with RRMS treated with IFN-beta, but we
found no association or interaction with HLA or the NAT1 variant.
PMID- 29343475
TI - Staff shortages force mental health trusts to cancel patient activities and close
wards, says King's Fund.
PMID- 29343474
TI - Doctors do not feel protected when things go wrong.
PMID- 29343476
TI - Role of Macrophage Socs3 in the Pathogenesis of Aortic Dissection.
AB - BACKGROUND: Aortic dissection (AD) is a life-threatening medical emergency caused
by the abrupt destruction of the intimomedial layer of the aortic walls. Given
that previous studies have reported the involvement of proinflammatory cytokine
interleukin-6 in AD pathogenesis, we investigated the role of signal transduction
and activator of transcription 3 signaling, a downstream pathway of interleukin-6
in macrophages in pathogenesis of AD. METHODS AND RESULTS: We characterized the
pathological and molecular events triggered by aortic stress, which can lead to
AD. Aortic stress on the suprarenal aorta because of infrarenal aorta stiffening
and angiotensin II infusion for 1 week caused focal medial rupture at the
branching point of the celiac trunk and superior mesenteric artery. This focal
medial rupture healed in 6 weeks in wild-type (WT) mice, but progressed to AD in
mice with macrophage-specific deletion of Socs3 gene (mSocs3-KO). mSocs3-KO mice
showed premature activation of cell proliferation, an inflammatory response, and
skewed differentiation of macrophages toward the tissue-destructive phenotype.
Concomitantly, they showed aberrant phenotypic modulation of smooth muscle cells
and transforming growth factor beta signaling, which are likely to participate in
tissue repair. Human AD samples revealed signal transduction and activator of
transcription 3 activation in adventitial macrophages adjacent to the site of
tissue destruction. CONCLUSIONS: These findings suggest that AD development is
preceded by focal medial rupture, in which macrophage Socs3 maintains proper
inflammatory response and differentiation of SMCs, thus promoting fibrotic
healing to prevent tissue destruction and AD development. Understanding the
sequence of the pathological and molecular events preceding AD development will
help predict and prevent AD development and progression.
PMID- 29343477
TI - Role of ASIC3, Nav1.7 and Nav1.8 in electroacupuncture-induced analgesia in a
mouse model of fibromyalgia pain.
AB - BACKGROUND: The mechanisms underlying fibromyalgia (FM) pain are not understood.
The US Food and Drug Administration has recommended three drugs for treating FM
namely, pregabalin, duloxetine and milnacipran; however, these medications are
associated with severe side effects. OBJECTIVE: To create a mouse model of FM
pain using dual injections of acidic saline to cause mechanical hyperalgesia and
test whether ASIC3, Nav1.7 and Nav1.8 are involved in this process and whether
electroacupuncture (EA) can reverse these phenomena. METHODS: The FM model was
established by injecting acidic saline twice into 40 ICR mice. The mice were
assigned to subgroups (n=8 each) treated with different EA frequencies (2, 15 and
50 Hz). ASIC3, Nav1.7 and Nav1.8 expression levels were measured by Western
blotting and immunohistochemistry. RESULTS: Significant mechanical hyperalgesia
was induced on day 8 in FM mice, which was reversed by 2, 15 and 50 Hz EA. ASIC3,
Nav1.7 and Nav1.8 protein levels increased significantly in both the dorsal root
ganglion and in the spinal cord of FM model mice. These changes were further
attenuated by 2, 15 and 50 Hz EA. CONCLUSION: Reduced nociceptive ASIC3, Nav1.7
and Nav1.8 proteins are involved in the preventive effects of EA against FM, and
this series of molecules may represent targets for FM treatment.
PMID- 29343478
TI - Treatment of gastrointestinal bleeding with idarucizumab in a patient receiving
dabigatran.
AB - PURPOSE: A case report describing use of idarucizumab for dabigatran reversal
without the use of hemostatic agents in a patient who developed acute upper
gastrointestinal (GI) bleeding while receiving triple antithrombotic therapy is
presented. SUMMARY: A 77-year-old man with a complex cardiac history presented to
the emergency room with chief complaints of black tarry stools and low blood
pressures for 4 days. His past medical history included recent percutaneous
coronary intervention (PCI) and drug-eluting stent (DES) placement, atrial
fibrillation, hypertension, hyperlipidemia, coronary artery disease, coronary
artery bypass graft surgery, stage 3 chronic kidney disease, and cholecystectomy.
His triple antithrombotic therapy consisted of aspirin, clopidogrel, and
dabigatran. The patient stated that his last dose of dabigatran was taken the
night before. Serum dabigatran levels were not measured. Due to suspicion of
acute upper GI bleeding, all antithrombotic agents were withheld. Treatment with
idarucizumab, i.v. pantoprazole, and blood transfusion was ordered. An upper
endoscopy was safely performed 24 hours later and revealed a minor Mallory-Weiss
tear. The patient was discharged 48 hours later with prescriptions for acid
suppressant and triple antithrombotic therapy; his melena had resolved before
discharge. At 14-week follow-up, the patient reported that his cardiologist had
deleted aspirin from his antithrombotic regimen. CONCLUSION: A patient who had
recently undergone PCI and DES placement and was receiving aspirin, clopidogrel,
and dabigatran for atrial fibrillation was successfully treated for acute GI
bleeding with idarucizumab without the use of a hemostatic agent.
PMID- 29343480
TI - Samiran Nundy: Tackling India's corruption.
PMID- 29343481
TI - Should all patients be asked about their sexual orientation?
PMID- 29343479
TI - Postsurgical prescriptions for opioid naive patients and association with
overdose and misuse: retrospective cohort study.
AB - OBJECTIVE: To quantify the effects of varying opioid prescribing patterns after
surgery on dependence, overdose, or abuse in an opioid naive population. DESIGN:
Retrospective cohort study. SETTING: Surgical claims from a linked medical and
pharmacy administrative database of 37 651 619 commercially insured patients
between 2008 and 2016. PARTICIPANTS: 1 015 116 opioid naive patients undergoing
surgery. MAIN OUTCOME MEASURES: Use of oral opioids after discharge as defined by
refills and total dosage and duration of use. The primary outcome was a composite
of misuse identified by a diagnostic code for opioid dependence, abuse, or
overdose. RESULTS: 568 612 (56.0%) patients received postoperative opioids, and a
code for abuse was identified for 5906 patients (0.6%, 183 per 100 000 person
years). Total duration of opioid use was the strongest predictor of misuse, with
each refill and additional week of opioid use associated with an adjusted
increase in the rate of misuse of 44.0% (95% confidence interval 40.8% to 47.2%,
P<0.001), and 19.9% increase in hazard (18.5% to 21.4%, P<0.001), respectively.
CONCLUSIONS: Each refill and week of opioid prescription is associated with a
large increase in opioid misuse among opioid naive patients. The data from this
study suggest that duration of the prescription rather than dosage is more
strongly associated with ultimate misuse in the early postsurgical period. The
analysis quantifies the association of prescribing choices on opioid misuse and
identifies levers for possible impact.
PMID- 29343484
TI - System to support patients with ongoing needs is "falling short on many fronts".
PMID- 29343482
TI - PAR1 biased signaling is required for activated protein C in vivo benefits in
sepsis and stroke.
AB - Activated protein C (APC) cleaves protease-activated receptor 1 (PAR1) in vitro
at R46 to initiate beneficial cell signaling; however, thrombin and APC can
cleave at R41. To elucidate PAR1-dependent aspects of the pharmacologic in vivo
mechanisms of APC, we generated C57BL/6 mouse strains carrying QQ41 or QQ46 point
mutations in PAR1 (F2r gene). Using these strains, we determined whether or not
recombinant murine signaling-selective APC mutants would reduce septic death or
provide neuroprotection against ischemic stroke when mice carried PAR1-homozygous
mutations that prevent cleavage at either R41 or R46. Intercrossing PAR1+/R46Q
mice generated expected numbers of PAR1+/+, PAR1+/R46Q, and R46Q/R46Q offspring
whereas intercrossing PAR1+/R41Q mice gave decreased R41Q/R41Q homozygotes
(resembling intercrossing PAR1+/PAR1-knockout mice). QQ41-PAR1 and QQ46-PAR1
brain endothelial cells showed the predicted retention or loss of cellular
responses to thrombin receptor-activating peptide, thrombin, or APC for each PAR1
mutation. In sepsis studies, exogenous APC reduced mortality from 50% to 10% in
Escherichia coli-induced pneumonia for wild-type (Wt) PAR1 and QQ41-PAR1 mice (P
< .01) but had no benefit for QQ46-PAR1 mice. In transient distal middle cerebral
artery occlusion stroke studies, exogenous APC significantly reduced infarct
size, edema, and neuronal apoptosis for Wt mice and QQ41-PAR1 mice but had no
detectable benefits for mice carrying QQ46-PAR1. In functional studies of
forelimb-asymmetry and foot-fault tests at 24 hours after stroke induction,
signaling-selective APC was beneficial for Wt and QQ41-PAR1 mice but not QQ46
PAR1 mice. These results support the concept that APC-induced, PAR1-dependent
biased signaling following R46 cleavage is central to the in vivo benefits of
APC.
PMID- 29343485
TI - Criminal and professional sanctions impede honesty and improvement.
PMID- 29343483
TI - NR4A1 and NR4A3 restrict HSC proliferation via reciprocal regulation of
C/EBPalpha and inflammatory signaling.
AB - Members of the NR4A subfamily of nuclear receptors have complex, overlapping
roles during hematopoietic cell development and also function as tumor
suppressors of hematologic malignancies. We previously identified NR4A1 and NR4A3
(NR4A1/3) as functionally redundant suppressors of acute myeloid leukemia (AML)
development. However, their role in hematopoietic stem cell (HSC) homeostasis
remains to be disclosed. Using a conditional Nr4a1/Nr4a3 knockout mouse (CDKO),
we show that codepletion of NR4A1/3 promotes acute changes in HSC homeostasis
including loss of HSC quiescence, accumulation of oxidative stress, and DNA
damage while maintaining stem cell regenerative and differentiation capacity.
Molecular profiling of CDKO HSCs revealed widespread upregulation of genetic
programs governing cell cycle and inflammation and an aberrant activation of the
interferon and NF-kappaB signaling pathways in the absence of stimuli.
Mechanistically, we demonstrate that NR4A1/3 restrict HSC proliferation in part
through activation of a C/EBPalpha-driven antiproliferative network by directly
binding to a hematopoietic-specific Cebpa enhancer and activating Cebpa
transcription. In addition, NR4A1/3 occupy the regulatory regions of NF-kappaB
regulated inflammatory cytokines, antagonizing the activation of NF-kappaB
signaling. Taken together, our results reveal a novel coordinate control of HSC
quiescence by NR4A1/3 through direct activation of C/EBPalpha and suppression of
activation of NF-kappaB-driven proliferative inflammatory responses.
PMID- 29343487
TI - Sixty seconds on . . . the Lansley diaries.
PMID- 29343488
TI - Commentary: Let's talk about sex.
PMID- 29343486
TI - Electronic cigarettes for smoking cessation.
PMID- 29343489
TI - GMC should deal forcefully with repeatedly dishonest doctors.
PMID- 29343491
TI - Mexicans head off spread of zoonotic tuberculosis.
PMID- 29343492
TI - Boris Johnson is criticised for repeating claims that NHS will benefit from
Brexit.
PMID- 29343493
TI - CCG criticises NHS England after being ordered to cut GP funding.
PMID- 29343495
TI - GMC erasure: it could have been me.
PMID- 29343496
TI - Trump administration halts "evidence based" treatment database.
PMID- 29343494
TI - Uncovering Genomic Regions Associated with Trypanosoma Infections in Wild
Populations of the Tsetse Fly Glossina fuscipes.
AB - Vector-borne diseases are responsible for > 1 million deaths every year but
genomic resources for most species responsible for their transmission are
limited. This is true for neglected diseases such as sleeping sickness (Human
African Trypanosomiasis), a disease caused by Trypanosoma parasites vectored by
several species of tseste flies within the genus Glossina We describe an
integrative approach that identifies statistical associations between trypanosome
infection status of Glossina fuscipes fuscipes (Gff) flies from Uganda, for which
functional studies are complicated because the species cannot be easily
maintained in laboratory colonies, and ~73,000 polymorphic sites distributed
across the genome. Then, we identify candidate genes involved in Gff trypanosome
susceptibility by taking advantage of genomic resources from a closely related
species, G. morsitans morsitans (Gmm). We compiled a comprehensive transcript
library from 72 published and unpublished RNAseq experiments of trypanosome
infected and uninfected Gmm flies, and improved the current Gmm transcriptome
assembly. This new assembly was then used to enhance the functional annotations
on the Gff genome. As a consequence, we identified 56 candidate genes in the
vicinity of the 18 regions associated with Trypanosoma infection status in Gff
Twenty-nine of these genes were differentially expressed (DE) among parasite
infected and uninfected Gmm, suggesting that their orthologs in Gff may correlate
with disease transmission. These genes were involved in DNA regulation,
neurophysiological functions, and immune responses. We highlight the power of
integrating population and functional genomics from related species to enhance
our understanding of the genetic basis of physiological traits, particularly in
nonmodel organisms.
PMID- 29343497
TI - Most medical practices are not parachutes: a citation analysis of practices felt
by biomedical authors to be analogous to parachutes.
AB - BACKGROUND: In a 2003 paper in BMJ, the authors made the tongue-in-cheek
observation that there are no randomized controlled trials (RCTs) of parachutes.
This paper has been widely read, cited and used to argue that RCTs are
impractical or unnecessary for some medical practices. We performed a study to
identify and evaluate claims that a medical practice is akin to a parachute.
METHODS: Using Google Scholar, we identified all citations to the 2003 paper. We
searched for claims that a specific practice was akin to a parachute. For each
practice, we identified the desired outcome of the practice, and searched Google
Scholar and ClinicalTrials.gov for RCTs that were conducted, ongoing, halted,
planned or unpublished. RESULTS: Of 822 articles citing the original paper, 35
(4.1%) argued that a medical practice was akin to a parachute. Eighteen of the 35
(51%) concerned mortality or live birth, and 17 (49%) concerned a lesser outcome.
For 22 practices (63%), we identified 1 or more RCTs: in 6 cases (27%), the
trials showed a statistically significant benefit of the practice; in 5 (23%),
the trials rejected the practice; in 5 (23%), the trials had mixed results; in 2
(9%), the trials were halted; and in 4 (18%), the trials were ongoing. Effect
size was calculated for 5 of the 6 practices for which RCTs gave positive
results, and the absolute risk reduction ranged from 11% to 30.8%, corresponding
to a number needed to treat of 3-9. INTERPRETATION: Although there is widespread
interest regarding the BMJ paper arguing that randomized trials are not necessary
for practices of clear benefit, there are few analogies in medicine. Most
parachute analogies in medicine are inappropriate, incorrect or misused.
PMID- 29343498
TI - The GPR120 agonist TUG-891 promotes metabolic health by stimulating mitochondrial
respiration in brown fat.
AB - Brown adipose tissue (BAT) activation stimulates energy expenditure in human
adults, which makes it an attractive target to combat obesity and related
disorders. Recent studies demonstrated a role for G protein-coupled receptor 120
(GPR120) in BAT thermogenesis. Here, we investigated the therapeutic potential of
GPR120 agonism and addressed GPR120-mediated signaling in BAT We found that
activation of GPR120 by the selective agonist TUG-891 acutely increases fat
oxidation and reduces body weight and fat mass in C57Bl/6J mice. These effects
coincided with decreased brown adipocyte lipid content and increased nutrient
uptake by BAT, confirming increased BAT activity. Consistent with these
observations, GPR120 deficiency reduced expression of genes involved in nutrient
handling in BAT Stimulation of brown adipocytes in vitro with TUG-891 acutely
induced O2 consumption, through GPR120-dependent and GPR120-independent
mechanisms. TUG-891 not only stimulated GPR120 signaling resulting in
intracellular calcium release, mitochondrial depolarization, and mitochondrial
fission, but also activated UCP1. Collectively, these data suggest that
activation of brown adipocytes with the GPR120 agonist TUG-891 is a promising
strategy to increase lipid combustion and reduce obesity.
PMID- 29343499
TI - A Population Phylogenetic View of Mitochondrial Heteroplasmy.
AB - The mitochondrion has recently emerged as an active player in myriad cellular
processes. Additionally, it was recently shown that >200 diseases are known to be
linked to variants in mitochondrial DNA or in nuclear genes interacting with
mitochondria. This has reinvigorated interest in its biology and population
genetics. Mitochondrial heteroplasmy, or genotypic variation of mitochondria
within an individual, is now understood to be common in humans and important in
human health. However, it is still not possible to make quantitative predictions
about the inheritance of heteroplasmy and its proliferation within the body,
partly due to the lack of an appropriate model. Here, we present a population
genetic framework for modeling mitochondrial heteroplasmy as a process that
occurs on an ontogenetic phylogeny, with genetic drift and mutation changing
heteroplasmy frequencies during the various developmental processes represented
in the phylogeny. Using this framework, we develop a Bayesian inference method
for inferring rates of mitochondrial genetic drift and mutation at different
stages of human life. Applying the method to previously published heteroplasmy
frequency data, we demonstrate a severe effective germline bottleneck comprised
of the cumulative genetic drift occurring between the divergence of germline and
somatic cells in the mother, and the separation of germ layers in the offspring.
Additionally, we find that the two somatic tissues we analyze here undergo tissue
specific bottlenecks during embryogenesis, less severe than the effective
germline bottleneck, and that these somatic tissues experience little additional
genetic drift during adulthood. We conclude with a discussion of possible
extensions of the ontogenetic phylogeny framework and its possible applications
to other ontogenetic processes in addition to mitochondrial heteroplasmy.
PMID- 29343500
TI - Cbfbeta2 controls differentiation of and confers homing capacity to prethymic
progenitors.
AB - Multipotent hematopoietic progenitors must acquire thymus-homing capacity to
initiate T lymphocyte development. Despite its importance, the transcriptional
program underlying this process remains elusive. Cbfbeta forms transcription
factor complexes with Runx proteins, and here we show that Cbfbeta2, encoded by
an RNA splice variant of the Cbfb gene, is essential for extrathymic
differentiation of T cell progenitors. Furthermore, Cbfbeta2 endows extrathymic
progenitors with thymus-homing capacity by inducing expression of the principal
thymus-homing receptor, Ccr9. This occurs via direct binding of Cbfbeta2 to cell
type-specific enhancers, as is observed in Rorgammat induction during
differentiation of lymphoid tissue inducer cells by activation of an intronic
enhancer. As in mice, an alternative splicing event in zebrafish generates a
Cbfbeta2-specific mRNA, important for ccr9 expression. Thus, despite
phylogenetically and ontogenetically variable sites of origin of T cell
progenitors, their robust thymus-homing capacity is ensured by an evolutionarily
conserved mechanism emerging from functional diversification of Runx
transcription factor complexes by acquisition of a novel splice variant.
PMID- 29343502
TI - Taking deterministic control of membrane protein monomer-dimer measurements.
PMID- 29343501
TI - Sequential BMP7/TGF-beta1 signaling and microbiota instruct mucosal Langerhans
cell differentiation.
AB - Mucosal Langerhans cells (LCs) originate from pre-dendritic cells and monocytes.
However, the mechanisms involved in their in situ development remain unclear.
Here, we demonstrate that the differentiation of murine mucosal LCs is a two-step
process. In the lamina propria, signaling via BMP7-ALK3 promotes translocation of
LC precursors to the epithelium. Within the epithelium, TGF-beta1 finalizes LC
differentiation, and ALK5 is crucial to this process. Moreover, the local
microbiota has a major impact on the development of mucosal LCs, whereas LCs in
turn maintain mucosal homeostasis and prevent tissue destruction. These results
reveal the differential and sequential role of TGF-beta1 and BMP7 in LC
differentiation and highlight the intimate interplay of LCs with the microbiota.
PMID- 29343503
TI - In the Histone Zone: The Mighty Eraser.
PMID- 29343504
TI - Canonical and Noncanonical Actions of Arabidopsis Histone Deacetylases in
Ribosomal RNA Processing.
AB - Ribosome biogenesis is a fundamental process required for all cellular
activities. Histone deacetylases play critical roles in many biological processes
including transcriptional repression and rDNA silencing. However, their function
in pre-rRNA processing remains poorly understood. Here, we discovered a
previously uncharacterized role of Arabidopsis thaliana histone deacetylase HD2C
in pre-rRNA processing via both canonical and noncanonical manners. HD2C
interacts with another histone deacetylase HD2B and forms homo- and/or hetero
oligomers in the nucleolus. Depletion of HD2C and HD2B induces a ribosome
biogenesis deficient phenotype and aberrant accumulation of 18S pre-rRNA
intermediates. Our genome-wide analysis revealed that HD2C binds and represses
the expression of key genes involved in ribosome biogenesis. Using RNA
immunoprecipitation and sequencing, we further uncovered a noncanonical mechanism
of HD2C directly associating with pre-rRNA and small nucleolar RNAs to regulate
rRNA methylation. Together, this study reveals a multifaceted role of HD2C in
ribosome biogenesis and provides mechanistic insights into how histone
deacetylases modulate rRNA maturation at the transcriptional and
posttranscriptional levels.
PMID- 29343506
TI - How to use... Procalcitonin.
AB - Diagnosing bacterial infection in the unwell or febrile child is a common
challenge faced by all paediatricians. Despite the advent of novel molecular
techniques, there is ongoing need for diagnostic assays with adequate performance
and turnaround time to facilitate safe clinical decision-making when bacterial
sepsis is suspected, such as whether to commence empirical treatment with
antibiotics. Procalcitonin is an established marker of infection that has a
potential role in the diagnosis and exclusion of serious or invasive bacterial
infection in neonates and children. Although enthusiastically adopted in many
countries and institutions, national guidance in the UK does not yet support its
routine use. This article reviews the relevant literature on the use of
procalcitonin measurement in common paediatric clinical scenarios.
PMID- 29343505
TI - Revisiting Criteria for Plant MicroRNA Annotation in the Era of Big Data.
AB - MicroRNAs (miRNAs) are ~21-nucleotide-long regulatory RNAs that arise from
endonucleolytic processing of hairpin precursors. Many function as essential
posttranscriptional regulators of target mRNAs and long noncoding RNAs. Alongside
miRNAs, plants also produce large numbers of short interfering RNAs (siRNAs),
which are distinguished from miRNAs primarily by their biogenesis (typically
processed from long double-stranded RNA instead of single-stranded hairpins) and
functions (typically via roles in transcriptional regulation instead of
posttranscriptional regulation). Next-generation DNA sequencing methods have
yielded extensive data sets of plant small RNAs, resulting in many miRNA
annotations. However, it has become clear that many miRNA annotations are
questionable. The sheer number of endogenous siRNAs compared with miRNAs has been
a major factor in the erroneous annotation of siRNAs as miRNAs. Here, we provide
updated criteria for the confident annotation of plant miRNAs, suitable for the
era of "big data" from DNA sequencing. The updated criteria emphasize replication
and the minimization of false positives, and they require next-generation
sequencing of small RNAs. We argue that improved annotation systems are needed
for miRNAs and all other classes of plant small RNAs. Finally, to illustrate the
complexities of miRNA and siRNA annotation, we review the evolution and functions
of miRNAs and siRNAs in plants.
PMID- 29343508
TI - Circular RNA VMA21 protects against intervertebral disc degeneration through
targeting miR-200c and X linked inhibitor-of-apoptosis protein.
AB - OBJECTIVES: Circular RNAs (circRNAs) have been proven to function as competing
endogenous RNAs to interact with microRNAs (miRNAs) and influence the expression
of miRNA target mRNAs. In this study, we investigated whether circRNAs could act
as competing endogenous RNAs to regulate the pathological process of
intervertebral disc degeneration (IVDD). METHODS: The role and mechanism of a
circRNA, circVMA21, in IVDD were explored in nucleus pulposus (NP) cells and
degenerative NP tissues from patients and rat models. The interaction between
circVMA21 and miR-200c as well as the target mRNA, X linked inhibitor-of
apoptosis protein (XIAP), was examined. RESULTS: The decreased expression of XIAP
in the inflammatory cytokines-treated NP cells and the degenerative NP tissues
was directly associated with excessive apoptosis and imbalance between anabolic
and catabolic factors of extracellular matrix. miR-200c regulated NP cell
viability and functions through inhibiting XIAP. circVMA21 acted as a sponge of
miR-200c and functioned in NP cells through targeting miR-200c and XIAP.
Intradiscal injection of circVMA21 alleviated IVDD in the rat model. CONCLUSIONS:
CircVMA21 could alleviate inflammatory cytokines-induced NP cell apoptosis and
imbalance between anabolism and catabolism of extracellular matrix through miR
200c-XIAP pathway. It provides a potentially effective therapeutic strategy for
IVDD.
PMID- 29343507
TI - Early and sustained efficacy with apremilast monotherapy in biological-naive
patients with psoriatic arthritis: a phase IIIB, randomised controlled trial
(ACTIVE).
AB - OBJECTIVE: Evaluate apremilast efficacy across various psoriatic arthritis (PsA)
manifestations beginning at week 2 in biological-naive patients with PsA.
METHODS: Patients were randomised (1:1) to apremilast 30 mg twice daily or
placebo. At week 16, patients whose swollen and tender joint counts had not
improved by >=10% were eligible for early escape. At week 24, all patients
received apremilast through week 52. RESULTS: Among 219 randomised patients
(apremilast: n=110; placebo: n=109), a significantly greater American College of
Rheumatology 20 response at week 16 (primary outcome) was observed with
apremilast versus placebo (38.2% (42/110) vs 20.2% (22/109); P=0.004); response
rates at week 2 (first assessment) were 16.4% (18/110) versus 6.4% (7/109)
(P=0.025). Improvements in other efficacy outcomes, including 28-joint count
Disease Activity Score (DAS-28) using C reactive protein (CRP), swollen joint
count, Health Assessment Questionnaire-Disability Index (HAQ-DI), enthesitis and
morning stiffness severity, were observed with apremilast at week 2. At week 16,
apremilast significantly reduced PsA disease activity versus placebo, with
changes in DAS-28 (CRP) (P<0.0001), HAQ-DI (P=0.023) and Gladman Enthesitis Index
(P=0.001). Improvements were maintained with continued treatment through week 52.
Over 52 weeks, apremilast's safety profile was consistent with prior phase 3
studies in psoriasis and PsA. During weeks 0-24, the incidence of protocol
defined diarrhoea was 11.0% (apremilast) and 8.3% (placebo); serious adverse
event rates were 2.8% (apremilast) and 4.6% (placebo). CONCLUSIONS: In biological
naive patients with PsA, onset of effect with apremilast was observed at week 2
and continued through week 52. The safety profile was consistent with previous
reports. TRIAL REGISTRATION NUMBER: NCT01925768; Results.
PMID- 29343511
TI - Response to: 'Remission or low disease activity as a target in systemic lupus
erythematosus' by Ugarte-Gil et al.
PMID- 29343510
TI - Limited radiographic progression and sustained reductions in MRI inflammation in
patients with axial spondyloarthritis: 4-year imaging outcomes from the RAPID
axSpA phase III randomised trial.
AB - OBJECTIVES: To report 4-year imaging outcomes in the RAPID-axSpA (NCT01087762)
study of patients with ankylosing spondylitis (AS) and non-radiographic axial
spondyloarthritis (nr-axSpA), treated with certolizumab pegol (CZP). METHODS:
This phase III, randomised trial was placebo-controlled and double-blind to week
24, dose-blind to week 48 and open-label to week 204. Patients fulfilling the
Assessment of Spondyloarthritis International Society (ASAS) axSpA criteria with
active disease were stratified (AS/nr-axSpA) according to the modified New York
(mNY) criteria at randomisation. Spinal radiographs were assessed using the
modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). MRI inflammation used
the Spondyloarthritis Research Consortium of Canada (SPARCC) score for sacroiliac
joints (SIJ) and the Berlin spinal score (remission defined as SPARCC <2 and
Berlin <=2, respectively). RESULTS: MRI improvements from baseline (BL) to week
12 were maintained to week 204 (SPARCC BL: AS=8.5, nr-axSpA=7.5; SPARCC week 204:
AS=1.3, nr-axSpA=2.4; Berlin BL: AS=7.4, nr-axSpA=4.4; Berlin week 204: AS=2.6,
nr-axSpA=1.9). 66.7% of patients with AS and 69.6% of patients with nr-axSpA with
BL SPARCC scores >=2, and 65.4% of patients with AS and 57.3% of patients with nr
axSpA with BL Berlin score >2, achieved remission at week 204. Mean mSASSS change
in AS from BL to week 204 was 0.98 (95% CI 0.34, 1.63); 0.67 (95% CI 0.21,1.13)
from BL to week 96; and 0.31 (95% CI 0.02,0.60) from week 96 to week 204.
Corresponding nr-axSpA changes were 0.06 (95% CI -0.17,0.28), -0.01 (95% CI
0.19,0.17) and 0.07 (95% CI -0.07,0.20). 4.5% of patients with nr-axSpA fulfilled
the mNY criteria at week 204, while 4.3% of patients with AS no longer did so.
CONCLUSIONS: In patients with CZP-treated axSpA, rapid decreases in spinal and
SIJ MRI inflammation were maintained to week 204. Overall, 4-year spinal
progression was low, with less progression during years 2-4 than 0-2.
Radiographic SIJ grading changes demonstrated limited progression. TRIAL
REGISTRATION NUMBER: NCT01087762; Post-results.
PMID- 29343509
TI - Efficacy and safety of tregalizumab in patients with rheumatoid arthritis and an
inadequate response to methotrexate: results of a phase IIb, randomised, placebo
controlled trial.
AB - OBJECTIVE: To evaluate the efficacy, biological activity and safety of
tregalizumab in patients with active rheumatoid arthritis (RA) and an inadequate
response to methotrexate (MTX). METHODS: 321 patients were randomised (1:1:1:1)
to placebo or tregalizumab 25, 100 or 200 mg once-weekly subcutaneously in
addition to MTX treatment. Responders at week 12 continued the same treatment,
and non-responders at week 12 were escalated to the next higher tregalizumab dose
level or re-randomised from placebo to active treatment. After 24 weeks, patients
could continue treatment with tregalizumab for 24 weeks (extension phase). The
primary endpoint was the American College of Rheumatology 20% improvement
criteria (ACR20) response rate at week 12. Safety and biological activity were
monitored through week 48. RESULTS: At week 12, ACR20 response rates were not
statistically significantly different between placebo and any of the tregalizumab
doses. Tregalizumab injections were well tolerated; most adverse events were mild
to moderate and comparable among treatment and placebo groups. Biological
activity was shown by dose-dependent CD4 downmodulation. CONCLUSION: Treatment
with tregalizumab did not show significant clinical efficacy in patients with
active RA compared with placebo but resulted in the expected biological effect on
CD4 modulation. Tregalizumab was generally well tolerated, and no new safety
findings were identified. TRIAL REGISTRATION NUMBER: NCT01999192; Results.
PMID- 29343512
TI - Response to: 'Neuropsychiatric lupus or not? Cerebral hypoperfusion by perfusion
weighted MRI in normal-appearing white matter in primary neuropsychiatric lupus
erythematosus' by Papadaki et al.
PMID- 29343513
TI - Using genetic buffering relationships identified in fission yeast to reveal
susceptibilities in cells lacking hamartin or tuberin function.
AB - Tuberous sclerosis complex is an autosomal dominant disorder characterized by
benign tumors arising from the abnormal activation of mTOR signaling in cells
lacking TSC1 (hamartin) or TSC2 (tuberin) activity. To expand the genetic
framework surrounding this group of growth regulators, we utilized the model
eukaryote Schizosaccharomyces pombe to uncover and characterize genes that buffer
the phenotypic effects of mutations in the orthologous tsc1 or tsc2 loci. Our
study identified two genes: fft3 (encoding a DNA helicase) and ypa1 (encoding a
peptidyle-prolyl cis/trans isomerase). While the deletion of fft3 or ypa1 has
little effect in wild-type fission yeast cells, their loss in tsc1Delta or
tsc2Delta backgrounds results in severe growth inhibition. These data suggest
that the inhibition of Ypa1p or Fft3p might represent an 'Achilles' heel' of
cells defective in hamartin/tuberin function. Furthermore, we demonstrate that
the interaction between tsc1/tsc2 and ypa1 can be rescued through treatment with
the mTOR inhibitor, torin-1, and that ypa1Delta cells are resistant to the
glycolytic inhibitor, 2-deoxyglucose. This identifies ypa1 as a novel upstream
regulator of mTOR and suggests that the effects of ypa1 loss, together with mTOR
activation, combine to result in a cellular maladaptation in energy metabolism
that is profoundly inhibitory to growth.
PMID- 29343514
TI - TRPM2 channel-mediated regulation of autophagy maintains mitochondrial function
and promotes gastric cancer cell survival via the JNK-signaling pathway.
AB - A lack of effective treatment is one of the main factors contributing to gastric
cancer-related death. Discovering effective targets and understanding their
underlying anti-cancer mechanism are key to achieving the best response to
treatment and to limiting side effects. Although recent studies have shown that
the cation channel transient receptor potential melastatin-2 (TRPM2) is crucial
for cancer cell survival, the exact mechanism remains unclear, limiting its
therapeutic potential. Here, using molecular and functional assays, we
investigated the role of TRPM2 in survival of gastric cancer cells. Our results
indicated that TRPM2 knockdown in AGS and MKN-45 cells decreases cell
proliferation and enhances apoptosis. We also observed that the TRPM2 knockdown
impairs mitochondrial metabolism, indicated by a decrease in basal and maximal
mitochondrial oxygen consumption rates and ATP production. These mitochondrial
defects coincided with a decrease in autophagy and mitophagy, indicated by
reduced levels of autophagy- and mitophagy-associated proteins (i.e. ATGs, LC3A/B
II, and BNIP3). Moreover, we found that TRPM2 modulates autophagy through a c-Jun
N-terminal kinase (JNK)-dependent and mechanistic target of rapamycin-independent
pathway. We conclude that in the absence of TRPM2, down-regulation of the JNK
signaling pathway impairs autophagy, ultimately causing the accumulation of
damaged mitochondria and death of gastric cancer cells. Of note, by inhibiting
cell proliferation and promoting apoptosis, the TRPM2 down-regulation enhanced
the efficacy of paclitaxel and doxorubicin in gastric cancer cells. Collectively,
we provide compelling evidence that TRPM2 inhibition may benefit therapeutic
approaches for managing gastric cancer.
PMID- 29343515
TI - Discovery of genes required for lipoteichoic acid glycosylation predicts two
distinct mechanisms for wall teichoic acid glycosylation.
AB - The bacterial cell wall is an important and highly complex structure that is
essential for bacterial growth because it protects bacteria from cell lysis and
environmental insults. A typical Gram-positive bacterial cell wall is composed of
peptidoglycan and the secondary cell wall polymers, wall teichoic acid (WTA) and
lipoteichoic acid (LTA). In many Gram-positive bacteria, LTA is a polyglycerol
phosphate chain that is decorated with d-alanine and sugar residues. However, the
function of and proteins responsible for the glycosylation of LTA are either
unknown or not well-characterized. Here, using bioinformatics, genetic, and NMR
spectroscopy approaches, we found that the Bacillus subtilis csbB and yfhO genes
are essential for LTA glycosylation. Interestingly, the Listeria monocytogenes
gene lmo1079, which encodes a YfhO homolog, was not required for LTA
glycosylation, but instead was essential for WTA glycosylation. LTA is
polymerized on the outside of the cell and hence can only be glycosylated
extracellularly. Based on the similarity of the genes coding for YfhO homologs
that are required in B. subtilis for LTA glycosylation or in L. monocytogenes for
WTA glycosylation, we hypothesize that WTA glycosylation might also occur
extracellularly in Listeria species. Finally, we discovered that in L.
monocytogenes, lmo0626 (gtlB) was required for LTA glycosylation, indicating that
the encoded protein has a function similar to that of YfhO, although the proteins
are not homologous. Together, our results enable us to propose an updated model
for LTA glycosylation and also indicate that glycosylation of WTA might occur
through two different mechanisms in Gram-positive bacteria.
PMID- 29343516
TI - Stat3-mediated alterations in lysosomal membrane protein composition.
AB - Lysosome function is essential in cellular homeostasis. In addition to its
recycling role, the lysosome has recently been recognized as a cellular signaling
hub. We have shown in mammary epithelial cells, both in vivo and in vitro, that
signal transducer and activator of transcription 3 (Stat3) modulates lysosome
biogenesis and can promote the release of lysosomal proteases that culminates in
cell death. To further investigate the impact of Stat3 on lysosomal function, we
conducted a proteomic screen of changes in lysosomal membrane protein components
induced by Stat3 using an iron nanoparticle enrichment strategy. Our results show
that Stat3 activation not only elevates the levels of known membrane proteins but
results in the appearance of unexpected factors, including cell surface proteins
such as annexins and flotillins. These data suggest that Stat3 may coordinately
regulate endocytosis, intracellular trafficking, and lysosome biogenesis to drive
lysosome-mediated cell death in mammary epithelial cells. The methodologies
described in this study also provide significant improvements to current
techniques used for the purification and analysis of the lysosomal proteome.
PMID- 29343518
TI - Fibroblast-Specific beta-Catenin Signaling Dictates the Outcome of AKI.
AB - AKI is a devastating condition with high morbidity and mortality. The pathologic
features of AKI are characterized by tubular injury, inflammation, and vascular
impairment. Whether fibroblasts in the renal interstitium have a role in the
pathogenesis of AKI is unknown. In this study, we investigated the role of
fibroblast-specific beta-catenin signaling in dictating the outcome of AKI, using
conditional knockout mice in which beta-catenin was specifically ablated in
fibroblasts (Gli1-beta-cat-/-). After ischemia-reperfusion injury (IRI), Gli1
beta-cat-/- mice had lower serum creatinine levels and less morphologic injury
than Gli1-beta-cat+/+ littermate controls. Moreover, we detected fewer apoptotic
cells, as well as decreased cytochrome C release; reduced expression of Bax,
FasL, and p53; and increased phosphorylation of Akt, in the Gli1-beta-cat-/-
kidneys. Gli1-beta-cat-/- kidneys also exhibited upregulated expression of
proliferating cell nuclear antigen and Ki-67, which are markers of cell
proliferation. Furthermore, Gli1-beta-cat-/- kidneys displayed suppressed NF
kappaB signaling and cytokine expression and reduced infiltration of inflammatory
cells. Notably, loss of beta-catenin in fibroblasts induced renal expression of
hepatocyte growth factor (HGF) and augmented the tyrosine phosphorylation of c
met receptor after IRI. In vitro, treatment with Wnt ligands or ectopic
expression of active beta-catenin inhibited HGF mRNA and protein expression and
repressed HGF promoter activity. Collectively, these results suggest that
fibroblast-specific beta-catenin signaling can control tubular injury and repair
in AKI by modulating HGF expression. Our studies uncover a previously
unrecognized role for interstitial fibroblasts in the pathogenesis of AKI.
PMID- 29343519
TI - Uremic Solute-Aryl Hydrocarbon Receptor-Tissue Factor Axis Associates with
Thrombosis after Vascular Injury in Humans.
AB - Individuals with CKD are particularly predisposed to thrombosis after vascular
injury. Using mouse models, we recently described indoxyl sulfate, a tryptophan
metabolite retained in CKD and an activator of tissue factor (TF) through aryl
hydrocarbon receptor (AHR) signaling, as an inducer of thrombosis across the CKD
spectrum. However, the translation of findings from animal models to humans is
often challenging. Here, we investigated the uremic solute-AHR-TF thrombosis axis
in two human cohorts, using a targeted metabolomics approach to probe a set of
tryptophan products and high-throughput assays to measure AHR and TF activity.
Analysis of baseline serum samples was performed from 473 participants with
advanced CKD from the Dialysis Access Consortium Clopidogrel Prevention of Early
AV Fistula Thrombosis trial. Participants with subsequent arteriovenous
thrombosis had significantly higher levels of indoxyl sulfate and kynurenine,
another uremic solute, and greater activity of AHR and TF, than those without
thrombosis. Pattern recognition analysis using the components of the thrombosis
axis facilitated clustering of the thrombotic and nonthrombotic groups. We
further validated these findings using 377 baseline samples from participants in
the Thrombolysis in Myocardial Infarction II trial, many of whom had CKD stage 2
3. Mechanistic probing revealed that kynurenine enhances thrombosis after
vascular injury in an animal model and regulates thrombosis in an AHR-dependent
manner. This human validation of the solute-AHR-TF axis supports further studies
probing its utility in risk stratification of patients with CKD and exploring its
role in other diseases with heightened risk of thrombosis.
PMID- 29343521
TI - T-type Ca2+ Channels: T for Targetable.
AB - In the past decade, T-type Ca2+ channels (TTCC) have been unveiled as key
regulators of cancer cell biology and thus have been proposed as chemotherapeutic
targets. Indeed, in vitro and in vivo studies indicate that TTCC pharmacologic
blockers have a negative impact on the viability of cancer cells and reduce tumor
size, respectively. Consequently mibefradil, a TTCC blocker approved in 1997 as
an antihypertensive agent but withdrawn in 1998 because of drug-drug
interactions, was granted 10 years later the orphan drug status by the FDA to
investigate its efficacy against brain, ovary, and pancreatic cancer. However,
the existence of different channel isoforms with distinct physiologic roles,
together with the lack of selective pharmacologic agents, has hindered a
conclusive chemotherapeutic evaluation. Here, we review the available evidence on
TTCC expression, value as prognostic markers, and effectiveness of their
pharmacologic blockade on cancer cells in vitro and in preclinical models. We
additionally summarize the status of clinical trials using mibefradil against
glioblastoma multiforme. Finally, we discuss the future perspectives and the
importance of further development of multidisciplinary research efforts on the
consideration of TTCCs as biomarkers or targetable molecules in cancer. Cancer
Res; 78(3); 603-9. (c)2018 AACR.
PMID- 29343520
TI - Evidence for the ISG15-Specific Deubiquitinase USP18 as an Antineoplastic Target.
AB - Ubiquitination and ubiquitin-like posttranslational modifications (PTM) regulate
activity and stability of oncoproteins and tumor suppressors. This implicates
PTMs as antineoplastic targets. One way to alter PTMs is to inhibit activity of
deubiquitinases (DUB) that remove ubiquitin or ubiquitin-like proteins from
substrate proteins. Roles of DUBs in carcinogenesis have been intensively
studied, yet few inhibitors exist. Prior work provides a basis for the ubiquitin
specific protease 18 (USP18) as an antineoplastic target. USP18 is the major DUB
that removes IFN-stimulated gene 15 (ISG15) from conjugated proteins. Prior work
discovered that engineered loss of USP18 increases ISGylation and in contrast to
its gain decreases cancer growth by destabilizing growth-regulatory proteins.
Loss of USP18 reduced cancer cell growth by triggering apoptosis. Genetic loss of
USP18 repressed cancer formation in engineered murine lung cancer models. The
translational relevance of USP18 was confirmed by finding its expression was
deregulated in malignant versus normal tissues. Notably, the recent elucidation
of the USP18 crystal structure offers a framework for developing an inhibitor to
this DUB. This review summarizes strong evidence for USP18 as a previously
unrecognized pharmacologic target in oncology. Cancer Res; 78(3); 587-92. (c)2018
AACR.
PMID- 29343517
TI - Early Infant Diet and Islet Autoimmunity in the TEDDY Study.
AB - OBJECTIVE: To examine duration of breastfeeding and timing of complementary foods
and risk of islet autoimmunity (IA). RESEARCH DESIGN AND METHODS: The
Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively
follows 8,676 children with increased genetic risk of type 1 diabetes (T1D) in
the U.S., Finland, Germany, and Sweden. This study included 7,563 children with
at least 9 months of follow-up. Blood samples were collected every 3 months from
birth to evaluate IA, defined as persistent, confirmed positive antibodies to
insulin (IAAs), GAD, or insulinoma antigen-2. We examined the associations
between diet and the risk of IA using Cox regression models adjusted for country,
T1D family history, HLA genotype, sex, and early probiotic exposure.
Additionally, we investigated martingale residuals and log-rank statistics to
determine cut points for ages of dietary exposures. RESULTS: Later introduction
of gluten was associated with increased risk of any IA and IAA. The hazard ratios
(HRs) for every 1-month delay in gluten introduction were 1.05 (95% CI 1.01,
1.10; P = 0.02) and 1.08 (95% CI 1.00, 1.16; P = 0.04), respectively. Martingale
residual analysis suggested that the age at gluten introduction could be grouped
as <4, 4-9, and >9 months. The risk of IA associated with introducing gluten
before 4 months of age was lower (HR 0.68; 95% CI 0.47, 0.99), and the risk of IA
associated with introducing it later than the age of 9 months was higher (HR
1.57; 95% CI 1.07, 2.31) than introduction between 4 and 9 months of age.
CONCLUSIONS: The timing of gluten-containing cereals and IA should be studied
further.
PMID- 29343522
TI - Polyol Pathway Links Glucose Metabolism to the Aggressiveness of Cancer Cells.
AB - Cancer cells alter their metabolism to support their malignant properties. In
this study, we report that the glucose-transforming polyol pathway (PP) gene aldo
keto-reductase-1-member-B1 (AKR1B1) strongly correlates with epithelial-to
mesenchymal transition (EMT). This association was confirmed in samples from lung
cancer patients and from an EMT-driven colon cancer mouse model with p53
deletion. In vitro, mesenchymal-like cancer cells showed increased AKR1B1 levels,
and AKR1B1 knockdown was sufficient to revert EMT. An equivalent level of EMT
suppression was measured by targeting the downstream enzyme sorbitol
dehydrogenase (SORD), further pointing at the involvement of the PP. Comparative
RNA sequencing confirmed a profound alteration of EMT in PP-deficient cells,
revealing a strong repression of TGFbeta signature genes. Excess glucose was
found to promote EMT through autocrine TGFbeta stimulation, while PP-deficient
cells were refractory to glucose-induced EMT. These data show that PP represents
a molecular link between glucose metabolism, cancer differentiation, and
aggressiveness, and may serve as a novel therapeutic target.Significance: A
glucose-transforming pathway in TGFbeta-driven epithelial-to-mesenchymal
transition provides novel mechanistic insights into the metabolic control of
cancer differentiation. Cancer Res; 78(7); 1604-18. (c)2018 AACR.
PMID- 29343523
TI - A Novel l-Asparaginase with low l-Glutaminase Coactivity Is Highly Efficacious
against Both T- and B-cell Acute Lymphoblastic Leukemias In Vivo.
AB - Acute lymphoblastic leukemia (ALL) is the most common type of pediatric cancer,
although about 4 of every 10 cases occur in adults. The enzyme drug l
asparaginase serves as a cornerstone of ALL therapy and exploits the asparagine
dependency of ALL cells. In addition to hydrolyzing the amino acid l-asparagine,
all FDA-approved l-asparaginases also have significant l-glutaminase coactivity.
Since several reports suggest that l-glutamine depletion correlates with many of
the side effects of these drugs, enzyme variants with reduced l-glutaminase
coactivity might be clinically beneficial if their antileukemic activity would be
preserved. Here we show that novel low l-glutaminase variants developed on the
backbone of the FDA-approved Erwinia chrysanthemi l-asparaginase were highly
efficacious against both T- and B-cell ALL, while displaying reduced acute
toxicity features. These results support the development of a new generation of
safer l-asparaginases without l-glutaminase activity for the treatment of human
ALL.Significance: A new l-asparaginase-based therapy is less toxic compared with
FDA-approved high l-glutaminase enzymes Cancer Res; 78(6); 1549-60. (c)2018 AACR.
PMID- 29343524
TI - Antitumor Properties of RAF709, a Highly Selective and Potent Inhibitor of RAF
Kinase Dimers, in Tumors Driven by Mutant RAS or BRAF.
AB - Resistance to the RAF inhibitor vemurafenib arises commonly in melanomas driven
by the activated BRAF oncogene. Here, we report antitumor properties of RAF709, a
novel ATP-competitive kinase inhibitor with high potency and selectivity against
RAF kinases. RAF709 exhibited a mode of RAF inhibition distinct from RAF monomer
inhibitors such as vemurafenib, showing equal activity against both RAF monomers
and dimers. As a result, RAF709 inhibited MAPK signaling activity in tumor models
harboring either BRAFV600 alterations or mutant N- and KRAS-driven signaling,
with minimal paradoxical activation of wild-type RAF. In cell lines and murine
xenograft models, RAF709 demonstrated selective antitumor activity in tumor cells
harboring BRAF or RAS mutations compared with cells with wild-type BRAF and RAS
genes. RAF709 demonstrated a direct pharmacokinetic/pharmacodynamic relationship
in in vivo tumor models harboring KRAS mutation. Furthermore, RAF709 elicited
regression of primary human tumor-derived xenograft models with BRAF, NRAS, or
KRAS mutations with excellent tolerability. Our results support further
development of inhibitors like RAF709, which represents a next-generation RAF
inhibitor with unique biochemical and cellular properties that enables antitumor
activities in RAS-mutant tumors.Significance: In an effort to develop RAF
inhibitors with the appropriate pharmacological properties to treat RAS mutant
tumors, RAF709, a compound with potency, selectivity, and in vivo properties, was
developed that will allow preclinical therapeutic hypothesis testing, but also
provide an excellent probe to further unravel the complexities of RAF kinase
signaling. Cancer Res; 78(6); 1537-48. (c)2018 AACR.
PMID- 29343525
TI - Lack of Remuscularization Following Transplantation of Human Embryonic Stem Cell
Derived Cardiovascular Progenitor Cells in Infarcted Nonhuman Primates.
AB - RATIONALE: Human pluripotent stem cell-derived cardiovascular progenitor cells
(hPSC-CVPCs) should be thoroughly investigated in large animal studies before
testing in clinical trials. OBJECTIVE: The main of this study is to clarify
whether hPSC-CVPCs can engraft for long time in the heart of primates after
myocardial infarction (MI) and compare the effectiveness and safety of
immunosuppression with cyclosporine alone or multiple-drug regimen (MDR)
containing cyclosporine, methylprednisolone, and basiliximab in cynomolgus
monkeys that had received intramyocardial injections of 1*107 EGFP (enhanced
green fluorescent protein)-expressing hPSC-CVPCs after MI. A third group of
animals received the immunosuppression MDR but without cell therapy after MI
(MI+MDR group). METHODS AND RESULTS: Measurements of EGFP gene levels and EGFP
immunofluorescence staining indicated that the hPSC-CVPC engraftment rate was
greater in the MI+MDR+CVPC group than that in the MI+cyclosporine+CVPC group.
However, even in the MI+MDR+CVPC group, no transplanted cells could be detected
at 140 days after transplantation. Concomitantly, immunofluorescent analysis of
CD3, CD4, and CD8 expression indicated that T-lymphocyte infiltration in the CVPC
transplanted hearts was less in the MDR-treated animals than in the cyclosporine
alone-treated animals. The recovery of left ventricular function on day 28 post
MI in the MI+MDR+CVPC group was better than that in the MI+MDR group. Apoptotic
cardiac cells were also less common in the MI+MDR+CVPC group than in the MI+MDR
group, although both immunosuppression regimens were associated with transient
hepatic dysfunction. CONCLUSIONS: This is the largest study of hPSCs in nonhuman
primates in cardiovascular field to date (n=32). Compared with cyclosporine
alone, MDR attenuates immune rejection and improves survival of hPSC-CVPCs in
primates; this is associated with less apoptosis of native cardiac cells and
better recovery of left ventricular function at 28 days. However, even with MDR,
transplanted hPSC-CVPCs do not engraft and do not survive at 140 days after
transplantation, thereby excluding remuscularization as a mechanism for the
functional effect.
PMID- 29343527
TI - Visual outcomes after chemotherapy for optic pathway glioma in children with and
without neurofibromatosis type 1: results of the International Society of
Paediatric Oncology (SIOP) Low-Grade Glioma 2004 trial UK cohort.
AB - AIMS: To report visual acuity (VA) outcomes following chemotherapy for optic
pathway glioma (OPG) in children with or without neurofibromatosis type-1 (NF1)
and to analyse associated risk factors. METHODS: A prospective, multicentre,
cohort study involving 155 children treated between September 2004 and December
2012. Initial and final VA was used for per-eye and per-subject analysis.
Correlation tests were performed to determine whether initial VA predicted final
VA. Logistic regression was used to determine whether age and tumour location
were associated risk factors. RESULTS: 90 children had complete ophthalmological
data. At initiation of chemotherapy, 26% and 49% of eyes with NF1-OPG and
sporadic OPG, respectively, had VA of >=0.7 log of the minimum angle of
resolution (logMAR). At final visit, per eye, 49% had <=0.2, 23% had 0.30-0.60
and 28% had VA>=0.70 logMAR in the NF1-OPG group. In the sporadic OPG group, per
eye, 32% had <=0.2, 11% had VA 0.30-0.60 and 57% had >=0.70 logMAR. Children with
sporadic OPG, per eye, were significantly less likely to have VA outcomes <=0.60
logMAR compared with children with NF1-OPG (OR=0.30; 95% CI 0.16 to 0.56;
P<0.0001). Per subject, VA improved in 24%, remained stable in 35% and worsened
in 41% of children with NF1-OPG and improved in 18%, remained stable in 43% and
worsened in 39% of children with sporadic OPG. CONCLUSIONS: Children with and
without NF1 demonstrated the same rate of VA improvement, stabilisation or
worsening; however, children with sporadic OPG had a poorer VA outcome. Better
initial VA, older age, absence of postchiasm tumour and presence of NF1 were
associated with improved or stable VA outcomes.
PMID- 29343526
TI - Mutations in CYB561 Causing a Novel Orthostatic Hypotension Syndrome.
AB - RATIONALE: Orthostatic hypotension is a common clinical problem, but the
underlying mechanisms have not been fully delineated. OBJECTIVE: We describe 2
families, with 4 patients in total, experiencing severe life-threatening
orthostatic hypotension because of a novel cause. METHODS AND RESULTS: As in
dopamine beta-hydroxylase deficiency, concentrations of norepinephrine and
epinephrine in the patients were low. Plasma dopamine beta-hydroxylase activity,
however, was normal, and the DBH gene had no mutations. Molecular genetic
analysis was performed to determine the underlying genetic cause. Homozygosity
mapping and exome and Sanger sequencing revealed pathogenic homozygous mutations
in the gene encoding cytochrome b561 (CYB561); a missense variant c.262G>A,
p.Gly88Arg in exon 3 in the Dutch family and a nonsense mutation (c.131G>A,
p.Trp44*) in exon 2 in the American family. Expression of CYB561 was investigated
using RNA from different human adult and fetal tissues, transcription of RNA into
cDNA, and real-time quantitative polymerase chain reaction. The CYB561 gene was
found to be expressed in many human tissues, in particular the brain. The CYB561
protein defect leads to a shortage of ascorbate inside the catecholamine
secretory vesicles leading to a functional dopamine beta-hydroxylase deficiency.
The concentration of the catecholamines and downstream metabolites was measured
in brain and adrenal tissue of 6 CYB561 knockout mice (reporter-tagged deletion
allele [post-Cre], genetic background C57BL/6NTac). The concentration of
norepinephrine and normetanephrine was decreased in whole-brain homogenates of
the CYB561(-/-) mice compared with wild-type mice (P<0.01), and the concentration
of normetanephrine and metanephrine was decreased in adrenal glands (P<0.01),
recapitulating the clinical phenotype. The patients responded favorably to
treatment with l-dihydroxyphenylserine, which can be converted directly to
norepinephrine. CONCLUSIONS: This study is the first to implicate cytochrome b561
in disease by showing that pathogenic mutations in CYB561 cause an as yet unknown
disease in neurotransmitter metabolism causing orthostatic hypotension.
PMID- 29343528
TI - Effect of intravitreal triamcinolone acetonide injection at the end of vitrectomy
for vitreous haemorrhage related to proliferative diabetic retinopathy.
AB - BACKGROUND/AIMS: To investigate whether intravitreal injection of triamcinolone
acetonide (IVTA) combined with vitrectomy prevents postoperative inflammation in
patients with vitreous haemorrhage (VH) due to proliferative diabetic retinopathy
(PDR). METHODS: This prospective, multicentre, randomised study conducted at
seven sites in Japan enrolled patients diagnosed as having VH following PDR.
Patients underwent vitrectomy with (IVTA+VIT group) or without (VIT group) IVTA
at the end of the surgery. Anterior flare intensity (AFI), central retinal
thickness (CRT), best-corrected visual acuity (BCVA) and intraocular pressure
(IOP) were measured before and at 3 days, 1 week, 1, 3 and 6 months after surgery
and compared. RESULTS: Number of patients who completed 6 months of follow-up was
40 and 41 in VIT group and IVTA+VIT group, respectively. AFI was significantly
higher in the VIT group than in the IVTA+VIT group at 3 days (P=0.033), 1 week
(P=0.019) and 1 month (P=0.037). There were no significant differences in CRT,
BCVA and IOP between the groups through the observational periods. In the cases
with macular oedema >350 um of CRT at 3 days, CRT was significantly lower in the
IVTA+VIT group than in the VIT group at 1 month (P=0.041). CONCLUSIONS: IVTA
combined with vitrectomy and cataract surgery contributed to inhibit the
postoperative inflammation in patients with VH due to PDR. The effect of IVTA in
the reduction of diabetic macular oedema may be limited to the early stage after
surgery. TRIAL REGISTRATION NUMBER: UMIN000020376, Post-results.
PMID- 29343529
TI - Quarter-Descemet membrane endothelial keratoplasty (Quarter-DMEK) for Fuchs
endothelial corneal dystrophy: 6 months clinical outcome.
AB - BACKGROUND/AIM: To assess the clinical outcome of the first series of Quarter
Descemet membrane endothelial keratoplasty (Quarter-DMEK), a potential hybrid
technique between 'descemetorhexis only' and conventional, circular DMEK.
METHODS: Prospective interventional case series at a tertiary referral centre.
Twelve eyes of 12 patients with central Fuchs endothelial corneal dystrophy
underwent Quarter-DMEK, that is, transplantation of one quadrant of a full
diameter DMEK graft, and were evaluated for best-corrected visual acuity (BCVA),
endothelial cell density (ECD) and complications up to 6 months postoperatively.
RESULTS: At 6 months postoperatively, all eyes reached a BCVA of >=20/40 (>=0.5),
11/12 (92%) of >=20/25 (>=0.8) and 6/12 (50%) of >=20/20 (>=1.0). Mean central
ECD decreased from 2867 (+/-161) cells/mm2 before to 1255 (+/-514) cells/mm2 at 1
month, 1058 (+/-455) cells/mm2 at 3 months and 968 (+/-427) cells/mm2 at 6 months
after surgery. Rebubbling was performed in 4/12 eyes (33%) within the first two
months. CONCLUSIONS: Quarter-DMEK may be a feasible procedure that allows for
visual outcomes similar to conventional, circular DMEK. The relatively large drop
in ECD within the first month may have resulted from more extensive endothelial
cell migration and/or measurement error (at the graft edges). If longer-term
outcomes would resemble those of conventional DMEK, Quarter-DMEK may potentially
quadruple the availability of endothelial grafts.
PMID- 29343530
TI - Peripapillary vascular changes in radiation optic neuropathy: an optical
coherence tomography angiography grading.
AB - AIMS: To investigate peripapillary vascular changes secondary to radiation optic
neuropathy (RON) using optical coherence tomography angiography (OCT-A) and to
propose a clinical grading of RON based on OCT-A findings. METHODS: Thirty-four
patients affected by RON were consecutively included. Each patient underwent best
corrected visual acuity measurement (ETDRS score) and OCT-A (Nidek RS-3000
Advance device, Nidek, Gamagori, Japan). The radial peripapillary capillary
plexus (RPCP) and the entire peripapillary capillary bed (EPCB) were analysed.
Quantitative analysis of the OCT-A images was performed using open-source
available ImageJ software (National Institutes of Health, Bethesda, Maryland,
USA). Qualitative analysis based on the proposed clinical grading (Grades 0-4)
was also performed by two masked graders. RESULTS: RON clinical (qualitative)
classification based on RPCP correlated with the quantitative RPCP perfusion
analysis (P=0.0001). RON clinical classification based on RPCP statistically
correlated with ETDRS score (P=0.001). RON clinical classification based on EPCB
also correlated with the quantitative EPCB perfusion analysis and ETDRS score
(P=0.02 and P=0.01, respectively). Compared with the clinical classification
based on EPCB, the qualitative classification based on RPCP reached a higher
intergrader agreement (0.96 and 0.86, respectively). CONCLUSION: OCT-A can be
used to detect RPCP abnormalities and to clinically classify RON with a high
interexaminer agreement. The proposed clinical classification is supported by the
quantitative analysis based on the use of specific images elaboration techniques
and correlates with visual acuity of the examined eyes.
PMID- 29343531
TI - Comparison of immunoblotting (IgA and IgG) and the Goldmann-Witmer coefficient
for diagnosis of ocular toxoplasmosis in immunocompetent patients.
AB - BACKGROUND: Ocular toxoplasmosis (OT) is a common cause of posterior uveitis
worldwide. The diagnosis of OT is based on clinical findings, but in most cases,
laboratory tests are required to confirm the aetiology, especially when other
diseases are suspected. The aim of this study was to evaluate which methods,
between the Goldmann-Witmer coefficient (GWC) and immunoblotting (IB) with both
IgG and IgA, in aqueous humour (AH) samples, can be the most sensitive to
diagnose OT, in current practice, especially in the first three weeks. METHODS:
Retrospectively reviewed records of 87 consecutive patients who had underwent AH
and serum sample, 42 patients with suspected OT and 45 patients with suspected
other ocular inflammatory diseases. All samples were analysed by both GWC and IB.
RESULTS: The GWC was significant in 47.6% of patients presenting with suspected
OT. The intraocular production of specific antibody anti-Toxoplasma gondii IgG
and IgA was revealed by IB in 71.4% of samples. The combination of these two
methods increased the sensitivity to 76.2%. Based on the interval between symptom
onset and paracentesis, IB had a greater sensitivity than GWC when sample of AH
was taken in the first three weeks (64.7% vs 23.5%, P=0.039), while the
difference between the sensitivity of IB and GWC was less important in cases with
an interval >3 weeks (76% vs 64% P=0.625). CONCLUSION: IB seems to be more useful
than the GWC if only one of these methods can be performed, especially during the
first three weeks after symptom onset.
PMID- 29343532
TI - Clinical Laboratory Practice Recommendations for the Use of Cardiac Troponin in
Acute Coronary Syndrome: Expert Opinion from the Academy of the American
Association for Clinical Chemistry and the Task Force on Clinical Applications of
Cardiac Bio-Markers of the International Federation of Clinical Chemistry and
Laboratory Medicine.
AB - This document is an essential companion to the third iteration of the National
Academy of Clinical Biochemistry [NACB,8 now the American Association for
Clinical Chemistry (AACC) Academy] Laboratory Medicine Practice Guidelines (LMPG)
on cardiac markers. The expert consensus recommendations were drafted in
collaboration with the International Federation of Clinical Chemistry and
Laboratory Medicine Task Force on Clinical Applications of Bio-Markers (IFCC TF
CB). We determined that there is sufficient clinical guidance on the use of
cardiac troponin (cTn) testing from clinical practice groups. Thus, in this
expert consensus document, we focused on clinical laboratory practice
recommendations for high-sensitivity (hs)-cTn assays. This document utilized the
expert opinion class of evidence to focus on the following 10 topics: (a) quality
control (QC) utilization, (b) validation of the lower reportable analytical
limits, (c) units to be used in reporting measurable concentrations for patients
and QC materials, (d) 99th percentile sex-specific upper reference limits to
define the reference interval; (e) criteria required to define hs-cTn assays, (f)
communication with clinicians and the laboratory's role in educating clinicians
regarding the influence of preanalytic and analytic problems that can confound
assay results, (g) studies on hs-cTn assays and how authors need to document
preanalytical and analytical variables, (h) harmonizing and standardizing assay
results and the role of commutable materials, (i) time to reporting of results
from sample receipt and sample collection, and (j) changes in hs-cTn
concentrations over time and the role of both analytical and biological
variabilities in interpreting results of serial blood collections.
PMID- 29343533
TI - How Clinical Laboratories May Improve Their Performance: The "High-Sensitivity"
Troponin Paradigm.
PMID- 29343534
TI - Effect of Acute Coronary Syndrome Probability on Diagnostic and Prognostic
Performance of High-Sensitivity Cardiac Troponin.
AB - BACKGROUND: There is concern that high-sensitivity cardiac troponin (hs-cTn) may
have low diagnostic accuracy in patients with low acute coronary syndrome (ACS)
probability. METHODS: We prospectively stratified patients presenting with acute
chest discomfort to the emergency department (ED) into 3 groups according to
their probability for ACS as assessed by the treating ED physician using a visual
analog scale: <=10%, 11% to 79%, and >=80%, reviewing all information available
at 90 min. hs-cTnT and hs-cTnI concentrations were determined in a blinded
fashion. Two independent cardiologists adjudicated the final diagnosis. RESULTS:
Among 3828 patients eligible for analysis, 1189 patients had low (<=10%)
probability for ACS. The incidence of non-ST-segment elevation myocardial
infarction (NSTEMI) increased from 1.3% to 12.2% and 54.8% in patients with low,
intermediate, and high ACS probability, respectively. The positive predictive
value of hs-cTnT and hs-cTnI was low in patients with low ACS probability and
increased with the incidence of NSTEMI, whereas the diagnostic accuracy of hs
cTnT and hs-cTnI for NSTEMI as quantified by the area under the curve (AUC) was
very high and comparable among all 3 strata, e.g., AUC hs-cTnI, 0.96 (95% CI,
0.94-0.97); 0.87 (95% CI, 0.85-0.89); and 0.89 (95% CI, 0.87-0.92), respectively.
Findings were validated using bootstrap analysis as an alternative methodology to
define ACS probability. Similarly, higher hs-cTnT/I concentrations independently
predicted all-cause mortality within 2 years (e.g., hs-cTnT hazard ratio, 1.39;
95% CI, 1.27-1.52), irrespective of ACS probability. CONCLUSIONS: Diagnostic and
prognostic accuracy and utility of hs-cTnT and hs-cTnI remain high in patients
with acute chest discomfort and low ACS probability.ClinicalTrials.gov
Identifier: NCT00470587.
PMID- 29343535
TI - Debates in Pain Management Testing.
PMID- 29343536
TI - Current and Emerging Multianalyte Assays with Algorithmic Analyses-Are
Laboratories Ready for Clinical Adoption?
PMID- 29343537
TI - A search for ceramide binding proteins using bifunctional lipid analogs yields
CERT-related protein StarD7.
AB - Ceramides are central intermediates of sphingolipid metabolism with dual roles as
mediators of cellular stress signaling and mitochondrial apoptosis. How ceramides
exert their cytotoxic effects is unclear and their poor solubility in water
hampers a search for specific protein interaction partners. Here, we report the
application of a photoactivatable and clickable ceramide analog, pacCer, to
identify ceramide binding proteins and unravel the structural basis by which
these proteins recognize ceramide. Besides capturing ceramide transfer protein
(CERT) from a complex proteome, our approach yielded CERT-related steroidogenic
acute regulatory protein D7 (StarD7) as novel ceramide binding protein. Previous
work revealed that StarD7 is required for efficient mitochondrial import of
phosphatidylcholine (PC) and serves a critical role in mitochondrial function and
morphology. Combining site-directed mutagenesis and photoaffinity labeling
experiments, we demonstrate that the steroidogenic acute regulatory transfer
domain of StarD7 harbors a common binding site for PC and ceramide. While StarD7
lacks robust ceramide transfer activity in vitro, we find that its ability to
shuttle PC between model membranes is specifically affected by ceramides. Besides
demonstrating the suitability of pacCer as a tool to hunt for ceramide binding
proteins, our data point at StarD7 as a candidate effector protein by which
ceramides may exert part of their mitochondria-mediated cytotoxic effects.
PMID- 29343538
TI - Impact of dietary omega3 polyunsaturated fatty acid supplementation on brown and
brite adipocyte function.
AB - The recent characterization of functional brown adipose tissue in adult humans
has opened new perspectives for regulation of energy expenditure with respect to
obesity and diabetes. Furthermore, dietary recommendations have taken into
account the insufficient dietary intake of omega3 PUFAs and the concomitant
excessive intake of omega6 PUFA associated with the occurrence of
overweight/obesity. We aimed to study whether omega3 PUFAs could play a role in
the recruitment and function of energy-dissipating brown/brite adipocytes. We
show that omega3 PUFA supplementation has a beneficial effect on the thermogenic
function of adipocytes. In vivo, a low dietary omega6:omega3 ratio improved the
thermogenic response of brown and white adipose tissues to beta3-adrenergic
stimulation. This effect was recapitulated in vitro by PUFA treatment of hMADS
adipocytes. We pinpointed the omega6-derived eicosanoid prostaglandin (PG)F2alpha
as the molecular origin because the effects were mimicked with a specific
PGF2alpha receptor agonist. PGF2alpha level in hMADS adipocytes was reduced in
response to omega3 PUFA supplementation. The recruitment of thermogenic
adipocytes is influenced by the local quantity of individual oxylipins, which is
controlled by the omega6:omega3 ratio of available lipids. In human nutrition,
energy homeostasis may thus benefit from the implementation of a more balanced
dietary omega6:omega3 ratio.
PMID- 29343539
TI - Buruli Ulcer: Review of a Neglected Skin Mycobacterial Disease.
AB - Buruli ulcer is caused by Mycobacterium ulcerans This neglected disease occurs in
scattered foci around the world, with a higher concentration of cases in West
Africa. The mycobacteria produce mycolactones that cause tissue necrosis. The
disease presents as a painless skin nodule that ulcerates as necrosis expands.
Finding acid-fast bacilli in smears or histopathology, culturing the
mycobacteria, and performing M. ulcerans PCR in presumptive cases confirm the
diagnosis. Medical treatment with oral rifampin and intramuscular streptomycin or
oral treatment with rifampin plus clarithromycin for 8 weeks is supported by the
World Health Organization. This review summarizes the epidemiology, pathogenesis,
clinical presentation, diagnostic tests, and advances in treatment.
PMID- 29343540
TI - Point-Counterpoint: Meningitis/Encephalitis Syndromic Testing in the Clinical
Laboratory.
AB - INTRODUCTIONSyndromic panels were first FDA cleared for detection of respiratory
pathogens in 2008. Since then, other panels have been approved by the FDA, and
most recently, the FilmArray meningitis/encephalitis panel (BioFire, Salt Lake
City, UT) has become available. This assay detects 14 targets within 1 h and
includes pathogens that typically cause different manifestations of infection,
although they infect the same organ system. Several studies have reported both
false-positive and false-negative results with this test, and all agree that the
cost is significant. As with other panels, health care systems have adopted
different strategies for offering this assay. Some have implemented strategies to
limit the use of the test to certain patient populations, others have elected not
to offer the test, and others have elected not to offer the test and instead
request that providers order specific PCRs for the pathogens that best fit the
patient's symptoms. In this Point-Counterpoint, Jennifer Dien Bard of the
Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles,
and of the Keck School of Medicine at the University of Southern California
explains why laboratories should offer these assays without restriction. Kevin
Alby of the University of Pennsylvania explains the concerns about the use of
these assays as first-line tests and why some limitations on their use might be
appropriate.
PMID- 29343541
TI - Immune Monitoring of Infectious Complications in Transplant Patients: an
Important Step towards Improved Clinical Management.
AB - Immune reconstitution following organ transplantation is absolutely critical in
preventing infectious complications. However, understanding the kinetics of
immune reconstitution and its potential impact on the clinical management of
transplant patients remains a significant challenge. Over the last decade,
various platform technologies have emerged which have provided important insights
into the immune reconstitution kinetics in transplant patients. However, many of
these technologies are too complicated and cumbersome to implement in a clinical
setting. In this issue of the Journal of Clinical Microbiology, Chiereghin et al.
(J. Clin. Microbiol. 56:e01040-17, 2018, https://doi.org/10.1128/JCM.01040-17)
report the results of their evaluation of the QuantiFERON-CMV (QFN-CMV) assay to
assess human cytomegalovirus (CMV)-specific CD8+ T-cell immunity in heart
transplant recipients as a prognostic tool. These studies showed that patients
with absence of global immune reactivity in the QFN-CMV assay were at a higher
risk of developing CMV after discontinuing antiviral prophylaxis. Furthermore,
failure to reconstitute CMV-specific immunity after resolution of the first
episode of viremia was associated with viral relapse. These observations, along
with other recent clinical studies utilizing the QFN-CMV assay, demonstrate that
systematic monitoring of antiviral immunity can be successfully used as a
prognostic tool and also to guide changes to the clinical management of
transplant patients.
PMID- 29343542
TI - Clinical Validation of SensiTest Colistin, a Broth Microdilution-Based Method To
Evaluate Colistin MICs.
AB - The global spread of multidrug-resistant Gram-negative bacteria has led to the
return of colistin for treating severe infections. Recently, different plasmid
mediated genes conferring resistance to this drug were described and reported
worldwide. International committees (EUCAST/CLSI) reevaluated inconsistencies
surrounding colistin antimicrobial susceptibility testing (AST), concluding that
broth microdilution (BMD) should serve as the reference method for AST. The
development of an accurate, reproducible commercial test based on BMD is
therefore highly desirable. SensiTest Colistin (STC), a BMD-based compact 4-test
panel containing the lyophilized antibiotic in 7 2-fold dilutions (0.25 to 16
MUg/ml) was here compared with the EUCAST-CLSI standard reference method (BMD)
and, for some isolates, with the automated Phoenix 100 system (PHX). A total of
353 bacterial strains were evaluated by two different laboratories; 137 isolates
were resistant to colistin (19 were intrinsically resistant, 83 harbored the mcr
1 gene). Essential agreement (EA) between STC and BMD was obtained for 339 out of
the 353 strains tested (96.0%). Overall categorical agreement was obtained for
349 out of the 353 strains analyzed (98.9%). Two major errors (MEs; 0.93%) and
two very major errors (VMEs; 1.46%) were documented. STC appeared to be a simple
but highly reliable test with good reproducibility even with panels stored at
room temperature or at 35 degrees C. Moreover, STC showed a good performance with
strains carrying the mcr-1 gene, with a 98.8% EA. As the secondary endpoint of
our study, VMEs for PHX were documented for 6 isolates (10%).
PMID- 29343543
TI - An Autoimmune Disease-Associated Risk Variant in the TNFAIP3 Gene Plays a
Protective Role in Brucellosis That Is Mediated by the NF-kappaB Signaling
Pathway.
AB - Naturally occurring functional variants (rs148314165 and rs200820567,
collectively referred to as TT>A) reduce the expression of the tumor necrosis
factor alpha-induced protein 3 (TNFAIP3) gene, a negative regulator of NF-kappaB
signaling, and predispose individuals to autoimmune disease. In this analysis, we
conducted a genetic association study of the TT>A variants in 1,209 controls and
150 patients with brucellosis, an infectious disease, and further assessed the
role of the variants in brucellosis. Our data demonstrated that the TT>A variants
were correlated with cases of brucellosis (P = 0.002; odds ratio [OR] = 0.34) and
with individuals who had a positive serum agglutination test (SAT) result (titer
of >1/160) (P = 4.2 * 10-6; OR = 0.23). A functional study demonstrated that
brucellosis patients carrying the protective allele (A) showed significantly
lower expression levels of the TNFAIP3 gene in their peripheral blood mononuclear
cells and showed increased NF-kappaB signaling. Monocytes from individuals
carrying the A allele that were stimulated with Brucella abortus had lower mRNA
levels of TNFAIP3 and produced more interleukin-10 (IL-10), IL-6, and IL-1beta
than those from TT allele carriers. These data showed that autoimmune disease
associated risk variants, TT>A, of the TNFAIP3 locus play a protective role in
the pathogenesis of brucellosis. Our findings suggest that a disruption of the
normal function of the TNFAIP3 gene might serve as a therapeutic target for the
treatment of brucellosis.
PMID- 29343544
TI - How to navigate counter dogmatic research findings.
PMID- 29343545
TI - Tolloid cleavage activates latent GDF8 by priming the pro-complex for
dissociation.
AB - Growth differentiation factor 8 (GDF8)/myostatin is a latent TGF-beta family
member that potently inhibits skeletal muscle growth. Here, we compared the
conformation and dynamics of precursor, latent, and Tolloid-cleaved GDF8 pro
complexes to understand structural mechanisms underlying latency and activation
of GDF8. Negative stain electron microscopy (EM) of precursor and latent pro
complexes reveals a V-shaped conformation that is unaltered by furin cleavage and
sharply contrasts with the ring-like, cross-armed conformation of latent TGF
beta1. Surprisingly, Tolloid-cleaved GDF8 does not immediately dissociate, but in
EM exhibits structural heterogeneity consistent with partial dissociation.
Hydrogen-deuterium exchange was not affected by furin cleavage. In contrast,
Tolloid cleavage, in the absence of prodomain-growth factor dissociation,
increased exchange in regions that correspond in pro-TGF-beta1 to the alpha1
helix, latency lasso, and beta1-strand in the prodomain and to the beta6'- and
beta7'-strands in the growth factor. Thus, these regions are important in
maintaining GDF8 latency. Our results show that Tolloid cleavage activates latent
GDF8 by destabilizing specific prodomain-growth factor interfaces and primes the
growth factor for release from the prodomain.
PMID- 29343546
TI - p62 filaments capture and present ubiquitinated cargos for autophagy.
AB - The removal of misfolded, ubiquitinated proteins is an essential part of the
protein quality control. The ubiquitin-proteasome system (UPS) and autophagy are
two interconnected pathways that mediate the degradation of such proteins. During
autophagy, ubiquitinated proteins are clustered in a p62-dependent manner and are
subsequently engulfed by autophagosomes. However, the nature of the protein
substrates targeted for autophagy is unclear. Here, we developed a reconstituted
system using purified components and show that p62 and ubiquitinated proteins
spontaneously coalesce into larger clusters. Efficient cluster formation requires
substrates modified with at least two ubiquitin chains longer than three moieties
and is based on p62 filaments cross-linked by the substrates. The reaction is
inhibited by free ubiquitin, K48-, and K63-linked ubiquitin chains, as well as by
the autophagosomal marker LC3B, suggesting a tight cross talk with general
proteostasis and autophagosome formation. Our study provides mechanistic insights
on how substrates are channeled into autophagy.
PMID- 29343547
TI - Molecular Pathways for Immune Recognition of Preproinsulin Signal Peptide in Type
1 Diabetes.
AB - The signal peptide region of preproinsulin (PPI) contains epitopes targeted by
HLA-A-restricted (HLA-A0201, A2402) cytotoxic T cells as part of the pathogenesis
of beta-cell destruction in type 1 diabetes. We extended the discovery of the PPI
epitope to disease-associated HLA-B*1801 and HLA-B*3906 (risk) and HLA-A*1101 and
HLA-B*3801 (protective) alleles, revealing that four of six alleles present
epitopes derived from the signal peptide region. During cotranslational
translocation of PPI, its signal peptide is cleaved and retained within the
endoplasmic reticulum (ER) membrane, implying it is processed for immune
recognition outside of the canonical proteasome-directed pathway. Using in vitro
translocation assays with specific inhibitors and gene knockout in PPI-expressing
target cells, we show that PPI signal peptide antigen processing requires signal
peptide peptidase (SPP). The intramembrane protease SPP generates cytoplasm
proximal epitopes, which are transporter associated with antigen processing
(TAP), ER-luminal epitopes, which are TAP independent, each presented by
different HLA class I molecules and N-terminal trimmed by ER aminopeptidase 1 for
optimal presentation. In vivo, TAP expression is significantly upregulated and
correlated with HLA class I hyperexpression in insulin-containing islets of
patients with type 1 diabetes. Thus, PPI signal peptide epitopes are processed by
SPP and loaded for HLA-guided immune recognition via pathways that are enhanced
during disease pathogenesis.
PMID- 29343548
TI - Loss of B-Cell Anergy in Type 1 Diabetes Is Associated With High-Risk HLA and Non
HLA Disease Susceptibility Alleles.
AB - Although B cells reactive with islet autoantigens are silenced by tolerance
mechanisms in healthy individuals, they can become activated and contribute to
the development of type 1 diabetes. We previously demonstrated that high-affinity
insulin-binding B cells (IBCs) occur exclusively in the anergic (BND) compartment
in peripheral blood of healthy subjects. Consistent with their activation early
in disease development, high-affinity IBCs are absent from the BND compartment of
some first-degree relatives (FDRs) as well as all patients with autoantibody
positive prediabetes and new-onset type 1 diabetes, a time when they are found in
pancreatic islets. Loss of BND IBCs is associated with a loss of the entire BND B
cell compartment consistent with provocation by an environmental trigger or
predisposing genetic factors. To investigate potential mechanisms operative in
subversion of B-cell tolerance, we explored associations between HLA and non-HLA
type 1 diabetes-associated risk allele genotypes and loss of BNDs in FDRs. We
found that high-risk HLA alleles and a subset of non-HLA risk alleles (i.e.,
PTPN2 [rs1893217], INS [rs689], and IKZF3 [rs2872507]), relevant to B- and T-cell
development and function are associated with loss of anergy. Hence, the results
suggest a role for risk-conferring alleles in perturbation of B-cell anergy
during development of type 1 diabetes.
PMID- 29343549
TI - Intracellular vesicle trafficking plays an essential role in mitochondrial
quality control.
AB - The Drosophila gene products Bet1, Slh and CG10144, predicted to function in
intracellular vesicle trafficking, were previously found to be essential for
mitochondrial nucleoid maintenance. Here we show that Slh and Bet1 co-operate to
maintain mitochondrial functions. In their absence, mitochondrial content,
membrane potential and respiration became abnormal, accompanied by mitochondrial
proteotoxic stress, but without direct effects on mtDNA. Immunocytochemistry
showed that both Slh and Bet1 are localized at the Golgi, together with a
proportion of Rab5-positive vesicles. Some Bet1, as well as a tiny amount of Slh,
co-fractionated with highly purified mitochondria, whilst live-cell imaging
showed coincidence of fluorescently tagged Bet1 with most Lysotracker-positive
and a small proportion of Mitotracker-positive structures. This 3-way association
was disrupted in cells knocked down for Slh, although co-localized lysosomal and
mitochondrial signals were still seen. Neither Slh nor Bet1 were required for
global mitophagy or endocytosis, but prolonged Slh knockdown resulted in G2
growth arrest, with increased cell diameter. These effects were shared with
knockdown of betaCOP but not of CG1044, Snap24 or Syntaxin6. Our findings
implicate vesicle sorting at the cis-Golgi in mitochondrial quality control.
PMID- 29343550
TI - Cdk1-dependent phosphoinhibition of a formin-F-BAR interaction opposes
cytokinetic contractile ring formation.
AB - In Schizosaccharomyces pombe, cytokinesis requires the assembly and constriction
of an actomyosin-based contractile ring (CR). A single essential formin, Cdc12,
localizes to the cell middle upon mitotic onset and nucleates the F-actin of the
CR. Cdc12 medial recruitment is mediated in part by its direct binding to the F
BAR scaffold Cdc15. Given that Cdc12 is hyperphosphorylated in M phase, we
explored whether Cdc12 phosphoregulation impacts its association with Cdc15
during mitosis. We found that Cdk1, a major mitotic kinase, phosphorylates Cdc12
on six N-terminal residues near the Cdc15-binding site, and phosphorylation on
these sites inhibits its interaction with the Cdc15 F-BAR domain. Consistent with
this finding, a cdc12 mutant with all six Cdk1 sites changed to phosphomimetic
residues (cdc12-6D) displays phenotypes similar to cdc12-P31A, in which the Cdc15
binding motif is disrupted; both show reduced Cdc12 at the CR and delayed CR
formation. Together, these results indicate that Cdk1 phosphorylation of formin
Cdc12 antagonizes its interaction with Cdc15 and thereby opposes Cdc12's CR
localization. These results are consistent with a general role for Cdk1 in
inhibiting cytokinesis until chromosome segregation is complete.
PMID- 29343551
TI - Two subunits of the exocyst, Sec3p and Exo70p, can function exclusively on the
plasma membrane.
AB - The exocyst is an octameric complex that tethers secretory vesicles to the plasma
membrane in preparation for fusion. We anchored each subunit with a transmembrane
(TM) domain at its N- or C-terminus. Only N-terminally anchored TM-Sec3p and C
terminally anchored Exo70p-TM proved functional. These findings orient the
complex with respect to the membrane and establish that Sec3p and Exo70p can
function exclusively on the membrane. The functions of TM-Sec3p and Exo70p-TM
were largely unaffected by blocks in endocytic recycling, suggesting that they
act on the plasma membrane rather than on secretory vesicles. Cytosolic pools of
the other exocyst subunits were unaffected in TM-sec3 cells, while they were
partially depleted in exo70-TM cells. Blocking actin-dependent delivery of
secretory vesicles in act1-3 cells results in loss of Sec3p from the purified
complex. Our results are consistent with a model in which Sec3p and Exo70p can
function exclusively on the plasma membrane while the other subunits are brought
to them on secretory vesicles.
PMID- 29343552
TI - Constitutive centromere-associated network contacts confer differential stability
on CENP-A nucleosomes in vitro and in the cell.
AB - Eukaryotic centromeres are defined by the presence of nucleosomes containing the
histone H3 variant, centromere protein A (CENP-A). Once incorporated at
centromeres, CENP-A nucleosomes are remarkably stable, exhibiting no detectable
loss or exchange over many cell cycles. It is currently unclear whether this
stability is an intrinsic property of CENP-A containing chromatin or whether it
arises from proteins that specifically associate with CENP-A chromatin. Two
proteins, CENP-C and CENP-N, are known to bind CENP-A human nucleosomes directly.
Here we test the hypothesis that CENP-C or CENP-N stabilize CENP-A nucleosomes in
vitro and in living cells. We show that CENP-N stabilizes CENP-A nucleosomes
alone and additively with CENP-C in vitro. However, removal of CENP-C and CENP-N
from cells, or mutating CENP-A so that it no longer interacts with CENP-C or CENP
N, had no effect on centromeric CENP-A stability in vivo. Thus, the stability of
CENP-A nucleosomes in chromatin does not arise solely from its interactions with
CENP-C or CENP-N.
PMID- 29343553
TI - Molecular Mechanisms of Biased and Probe-Dependent Signaling at CXC-Motif
Chemokine Receptor CXCR3 Induced by Negative Allosteric Modulators.
AB - Our recent explorations of allosteric modulators with improved properties
resulted in the identification of two biased negative allosteric modulators,
BD103 (N-1-{[3-(4-ethoxyphenyl)-4-oxo-3,4-dihydropyrido[2,3-d]pyrimi
din2yl]ethyl}-4-(4-fluorobutoxy)-N-[(1-methylpiperidin-4-yl)methyl}]butanamide)
and BD064 (5-[(N-{1-[3-(4-ethoxyphenyl)-4-oxo-3,4-dihydropyrido[2,3-d]pyrimidin-2
yl]ethyl-2-[4-fluoro-3-(trifluoromethyl)phenyl]acetamido)methyl]-2
fluorophenyl}boronic acid), that exhibited probe-dependent inhibition of CXC
motif chemokine receptor CXCR3 signaling. With the intention to elucidate the
structural mechanisms underlying their selectivity and probe dependence, we used
site-directed mutagenesis combined with homology modeling and docking to identify
amino acids of CXCR3 that contribute to modulator binding, signaling, and
transmission of cooperativity. With the use of allosteric radioligand RAMX3
([3H]N-{1-[3-(4-ethoxyphenyl)-4-oxo-3,4-dihydropyrido[2,3-d]pyrimidin-2-yl]ethyl}
2-[4-fluoro-3-(trifluoromethyl)phenyl]-N-[(1-methylpiperidin-4
yl)methyl]acetamide), we identified that F1313.32 and Y3087.43 contribute
specifically to the binding pocket of BD064, whereas D1864.60 solely participates
in the stabilization of binding conformation of BD103. The influence of mutations
on the ability of negative allosteric modulators to inhibit chemokine-mediated
activation (CXCL11 and CXCL10) was assessed with the bioluminescence resonance
energy transfer-based cAMP and beta-arrestin recruitment assay. Obtained data
revealed complex molecular mechanisms governing biased and probe-dependent
signaling at CXCR3. In particular, F1313.32, S3047.39, and Y3087.43 emerged as
key residues for the compounds to modulate the chemokine response. Notably,
D1864.60, W2686.48, and S3047.39 turned out to play a role in signal pathway
selectivity of CXCL10, as mutations of these residues led to a G protein-active
but beta-arrestin-inactive conformation. These diverse effects of mutations
suggest the existence of ligand- and pathway-specific receptor conformations and
give new insights in the sophisticated signaling machinery between allosteric
ligands, chemokines, and their receptors, which can provide a powerful platform
for the development of new allosteric drugs with improved pharmacological
properties.
PMID- 29343555
TI - Antagonism of Integrin CD11b Affords Protection against Endotoxin Shock and
Polymicrobial Sepsis via Attenuation of HMGB1 Nucleocytoplasmic Translocation and
Extracellular Release.
AB - High mobility group box 1 (HMGB1), a chromatin-binding nuclear protein, plays a
critical role in sepsis by acting as a key "late-phase" inflammatory mediator.
Integrin CD11b is essential for inflammatory cell activation and migration, thus
mediating inflammatory responses. However, it is unclear whether CD11b
participates in the development of sepsis. In this study, we report that CD11b
contributes to LPS-induced endotoxin shock and microbial sepsis, as antagonism of
CD11b with the CD11b blocking Ab or CD11b inhibitor Gu-4 protects mice against
LPS- and microbial sepsis-related lethality, which is associated with
significantly diminished serum HMGB1 levels. Consistent with this, CD11b
deficient mice were more resistant to microbial sepsis with a much lower serum
HMGB1 level compared with wild-type mice. Pharmacological blockage and genetic
knockdown/knockout of CD11b in murine macrophages hampered LPS-stimulated HMGB1
nucleocytoplasmic translocation and extracellular release. Furthermore, silencing
CD11b interrupted the interaction of HMGB1 with either a nuclear export factor
chromosome region maintenance 1 or classical protein kinase C and inhibited
classical protein kinase C-induced HMGB1 phosphorylation, the potential
underlying mechanism(s) responsible for CD11b blockage-induced suppression of
HMGB1 nucleocytoplasmic translocation and subsequent extracellular release. Thus,
our results highlight that CD11b contributes to the development of sepsis,
predominantly by facilitating nucleocytoplasmic translocation and active release
of HMGB1.
PMID- 29343554
TI - Biased Generation and In Situ Activation of Lung Tissue-Resident Memory CD4 T
Cells in the Pathogenesis of Allergic Asthma.
AB - Asthma is a chronic inflammatory disease mediated by allergen-specific CD4 T
cells that promote lung inflammation through recruitment of cellular effectors
into the lung. A subset of lung T cells can persist as tissue-resident memory T
cells (TRMs) following infection and allergen induction, although the generation
and role of TRM in asthma persistence and pathogenesis remain unclear. In this
study, we used a mouse model of chronic exposure to intranasal house dust mite
(HDM) extract to dissect how lung TRMs are generated and function in the
persistence and pathogenesis of allergic airway disease. We demonstrate that both
CD4+ and CD8+ T cells infiltrate into the lung tissue during acute HDM exposure;
however, only CD4+ TRMs, and not CD8+ TRMs, persist long term following cessation
of HDM administration. Lung CD4+ TRMs are localized around airways and are
rapidly reactivated upon allergen re-exposure accompanied by the rapid induction
of airway hyperresponsiveness independent of circulating T cells. Lung CD4+ TRM
activation to HDM challenge is also accompanied by increased recruitment and
activation of dendritic cells in the lungs. Our results indicate that lung CD4+
TRMs can perpetuate allergen-specific sensitization and direct early inflammatory
signals that promote rapid lung pathology, suggesting that targeting lung CD4+
TRMs could have therapeutic benefit in alleviating recurrent asthma episodes.
PMID- 29343556
TI - RASA1/NF1-Mutant Lung Cancer: Racing to the Clinic?
AB - Although mutation of NF1 has been described in non-small cell lung cancer
(NSCLC), co-mutation with RASA1, another Ras-GTPase activating protein (RasGAP),
defines a novel genetically defined subclass of NSCLC. RASA1/NF1-mutant cell
lines are highly sensitive to MEK inhibitors, warranting clinical evaluation of
MAPK inhibition in this subclass of patients. Clin Cancer Res; 24(6); 1243-5.
(c)2018 AACRSee related article by Hayashi et al., p. 1436.
PMID- 29343558
TI - Postcranial diversity and recent ecomorphic impoverishment of North American gray
wolves.
AB - Recent advances in genomics and palaeontology have begun to unravel the complex
evolutionary history of the gray wolf, Canis lupus Still, much of their
phenotypic variation across time and space remains to be documented. We examined
the limb morphology of the fossil and modern North American gray wolves from the
late Quaternary ( 0.95) with experimental data
within the range of (thermal and radiation) doses tested (0-40 CEM43, 0-5 Gy).
The proposed framework offers flexibility for modelling multimodality treatment
combinations in different scenarios. It may therefore provide an important step
towards the modelling of personalized therapies using a virtual patient tumour.
PMID- 29343633
TI - Hydrogel biomaterials and their therapeutic potential for muscle injuries and
muscular dystrophies.
AB - Muscular diseases such as muscular dystrophies and muscle injuries constitute a
large group of ailments that manifest as muscle weakness, atrophy or fibrosis.
Although cell therapy is a promising treatment option, the delivery and retention
of cells in the muscle is difficult and prevents sustained regeneration needed
for adequate functional improvements. Various types of biomaterials with
different physical and chemical properties have been developed to improve the
delivery of cells and/or growth factors for treating muscle injuries. Hydrogels
are a family of materials with distinct advantages for use as cell delivery
systems in muscle injuries and ailments, including their mild processing
conditions, their similarities to natural tissue extracellular matrix, and their
ability to be delivered with less invasive approaches. Moreover, hydrogels can be
made to completely degrade in the body, leaving behind their biological payload
in a process that can enhance the therapeutic process. For these reasons,
hydrogels have shown great potential as cell delivery matrices. This paper
reviews a few of the hydrogel systems currently being applied together with cell
therapy and/or growth factor delivery to promote the therapeutic repair of muscle
injuries and muscle wasting diseases such as muscular dystrophies.
PMID- 29343636
TI - Non-cell autonomous control of precerebellar neuron migration by Slit and Robo
proteins.
AB - During development, precerebellar neurons migrate tangentially from the dorsal
hindbrain to the floor plate. Their axons cross it but their cell bodies stop
their ventral migration upon reaching the midline. It has previously been shown
that Slit chemorepellents and their receptors, Robo1 and Robo2, might control the
migration of precerebellar neurons in a repulsive manner. Here, we have used a
conditional knockout strategy in mice to test this hypothesis. We show that the
targeted inactivation of the expression of Robo1 and Robo2 receptors in
precerebellar neurons does not perturb their migration and that they still stop
at the midline. The selective ablation of the expression of all three Slit
proteins in floor-plate cells has no effect on pontine neurons and only induces
the migration of a small subset of inferior olivary neurons across the floor
plate. Likewise, we show that the expression of Slit proteins in the facial
nucleus is dispensable for pontine neuron migration. Together, these results show
that Robo1 and Robo2 receptors act non-cell autonomously in migrating
precerebellar neurons and that floor-plate signals, other than Slit proteins,
must exist to prevent midline crossing.
PMID- 29343638
TI - Commissural neurons transgress the CNS/PNS boundary in absence of ventricular
zone-derived netrin 1.
AB - During the development of the central nervous system (CNS), only motor axons
project into peripheral nerves. Little is known about the cellular and molecular
mechanisms that control the development of a boundary at the CNS surface and
prevent CNS neuron emigration from the neural tube. It has previously been shown
that a subset of spinal cord commissural axons abnormally invades sensory nerves
in Ntn1 hypomorphic embryos and Dcc knockouts. However, whether netrin 1 also
plays a similar role in the brain is unknown. In the hindbrain, precerebellar
neurons migrate tangentially under the pial surface, and their ventral migration
is guided by netrin 1. Here, we show that pontine neurons and inferior olivary
neurons, two types of precerebellar neurons, are not confined to the CNS in Ntn1
and Dcc mutant mice, but that they invade the trigeminal, auditory and vagus
nerves. Using a Ntn1 conditional knockout, we show that netrin 1, which is
released at the pial surface by ventricular zone progenitors is responsible for
the CNS confinement of precerebellar neurons. We propose, that netrin 1
distribution sculpts the CNS boundary by keeping CNS neurons in netrin 1-rich
domains.
PMID- 29343639
TI - Neural migration: re-evaluating Slit and Robo.
PMID- 29343637
TI - Tyrosine phosphorylation and proteolytic cleavage of Notch are required for non
canonical Notch/Abl signaling in Drosophila axon guidance.
AB - Notch signaling is required for the development and physiology of nearly every
tissue in metazoans. Much of Notch signaling is mediated by transcriptional
regulation of downstream target genes, but Notch controls axon patterning in
Drosophila by local modulation of Abl tyrosine kinase signaling, via direct
interactions with the Abl co-factors Disabled and Trio. Here, we show that Notch
Abl axonal signaling requires both of the proteolytic cleavage events that
initiate canonical Notch signaling. We further show that some Notch protein is
tyrosine phosphorylated in Drosophila, that this form of the protein is
selectively associated with Disabled and Trio, and that relevant tyrosines are
essential for Notch-dependent axon patterning but not for canonical Notch
dependent regulation of cell fate. Based on these data, we propose a model for
the molecular mechanism by which Notch controls Abl signaling in Drosophila
axons.
PMID- 29343640
TI - Single-cell transcriptomics of the developing lateral geniculate nucleus reveals
insights into circuit assembly and refinement.
AB - Coordinated changes in gene expression underlie the early patterning and cell
type specification of the central nervous system. However, much less is known
about how such changes contribute to later stages of circuit assembly and
refinement. In this study, we employ single-cell RNA sequencing to develop a
detailed, whole-transcriptome resource of gene expression across four time points
in the developing dorsal lateral geniculate nucleus (LGN), a visual structure in
the brain that undergoes a well-characterized program of postnatal circuit
development. This approach identifies markers defining the major LGN cell types,
including excitatory relay neurons, oligodendrocytes, astrocytes, microglia, and
endothelial cells. Most cell types exhibit significant transcriptional changes
across development, dynamically expressing genes involved in distinct processes
including retinotopic mapping, synaptogenesis, myelination, and synaptic
refinement. Our data suggest that genes associated with synapse and circuit
development are expressed in a larger proportion of nonneuronal cell types than
previously appreciated. Furthermore, we used this single-cell expression atlas to
identify the Prkcd-Cre mouse line as a tool for selective manipulation of relay
neurons during a late stage of sensory-driven synaptic refinement. This
transcriptomic resource provides a cellular map of gene expression across several
cell types of the LGN, and offers insight into the molecular mechanisms of
circuit development in the postnatal brain.
PMID- 29343641
TI - Degradation of FBXO31 by APC/C is regulated by AKT- and ATM-mediated
phosphorylation.
AB - The F-box protein FBXO31 is a tumor suppressor that is encoded in 16q24.3, for
which there is loss of heterozygosity in various solid tumors. FBXO31 serves as
the substrate-recognition component of the SKP/Cullin/F-box protein class of E3
ubiquitin ligases and has been shown to direct degradation of pivotal cell-cycle
regulatory proteins including cyclin D1 and the p53 antagonist MDM2. FBXO31
levels are normally low but increase substantially following genotoxic stress
through a mechanism that remains to be determined. Here we show that the low
levels of FBXO31 are maintained through proteasomal degradation by anaphase
promoting complex/cyclosome (APC/C). We find that the APC/C coactivators CDH1 and
CDC20 bind to a destruction-box (D-box) motif present in FBXO31 to promote its
polyubiquitination and degradation in a cell-cycle-regulated manner, which
requires phosphorylation of FBXO31 on serine-33 by the prosurvival kinase AKT.
Following genotoxic stress, phosphorylation of FBXO31 on serine-278 by another
kinase, the DNA damage kinase ATM, results in disruption of its interaction with
CDH1 and CDC20, thereby preventing FBXO31 degradation. Collectively, our results
reveal how alterations in FBXO31 phosphorylation, mediated by AKT and ATM,
underlie physiological regulation of FBXO31 levels in unstressed and
genotoxically stressed cells.
PMID- 29343642
TI - Mechanogenetics for the remote and noninvasive control of cancer immunotherapy.
AB - While cell-based immunotherapy, especially chimeric antigen receptor (CAR)
expressing T cells, is becoming a paradigm-shifting therapeutic approach for
cancer treatment, there is a lack of general methods to remotely and
noninvasively regulate genetics in live mammalian cells and animals for cancer
immunotherapy within confined local tissue space. To address this limitation, we
have identified a mechanically sensitive Piezo1 ion channel (mechanosensor) that
is activatable by ultrasound stimulation and integrated it with engineered
genetic circuits (genetic transducer) in live HEK293T cells to convert the
ultrasound-activated Piezo1 into transcriptional activities. We have further
engineered the Jurkat T-cell line and primary T cells (peripheral blood
mononuclear cells) to remotely sense the ultrasound wave and transduce it into
transcriptional activation for the CAR expression to recognize and eradicate
target tumor cells. This approach is modular and can be extended for remote
controlled activation of different cell types with high spatiotemporal precision
for therapeutic applications.
PMID- 29343643
TI - Pyridoxal-5'-phosphate as an oxygenase cofactor: Discovery of a carboxamide
forming, alpha-amino acid monooxygenase-decarboxylase.
AB - Capuramycins are antimycobacterial antibiotics that consist of a modified
nucleoside named uridine-5'-carboxamide (CarU). Previous biochemical studies have
revealed that CarU is derived from UMP, which is first converted to uridine-5'
aldehyde in a reaction catalyzed by the dioxygenase CapA and subsequently to 5'-C
glycyluridine (GlyU), an unusual beta-hydroxy-alpha-amino acid, in a reaction
catalyzed by the pyridoxal-5'-phosphate (PLP)-dependent transaldolase CapH. The
remaining steps that are necessary to furnish CarU include decarboxylation, O
atom insertion, and oxidation. We demonstrate that Cap15, which has sequence
similarity to proteins annotated as bacterial, PLP-dependent l-seryl-tRNA(Sec)
selenium transferases, is the sole catalyst responsible for complete conversion
of GlyU to CarU. Using a complementary panel of in vitro assays, Cap15 is shown
to be dependent upon substrates O2 and (5'S,6'R)-GlyU, the latter of which was
unexpected given that (5'S,6'S)-GlyU is the isomeric product of the transaldolase
CapH. The two products of Cap15 are identified as the carboxamide-containing CarU
and CO2 While known enzymes that catalyze this type of chemistry, namely alpha
amino acid 2-monooxygenase, utilize flavin adenine dinucleotide as the redox
cofactor, Cap15 remarkably requires only PLP. Furthermore, Cap15 does not produce
hydrogen peroxide and is shown to directly incorporate a single O atom from O2
into the product CarU and thus is an authentic PLP-dependent monooxygenase. In
addition to these unusual discoveries, Cap15 activity is revealed to be dependent
upon the inclusion of phosphate. The biochemical characteristics along with
initiatory mechanistic studies of Cap15 are reported, which has allowed us to
assign Cap15 as a PLP-dependent (5'S,6'R)-GlyU:O2 monooxygenase-decarboxylase.
PMID- 29343644
TI - Identification of genes required for Mycobacterium abscessus growth in vivo with
a prominent role of the ESX-4 locus.
AB - Mycobacterium abscessus, a rapidly growing mycobacterium (RGM) and an
opportunistic human pathogen, is responsible for a wide spectrum of clinical
manifestations ranging from pulmonary to skin and soft tissue infections. This
intracellular organism can resist the bactericidal defense mechanisms of amoebae
and macrophages, an ability that has not been observed in other RGM. M. abscessus
can up-regulate several virulence factors during transient infection of amoebae,
thereby becoming more virulent in subsequent respiratory infections in mice.
Here, we sought to identify the M. abscessus genes required for replication
within amoebae. To this end, we constructed and screened a transposon (Tn)
insertion library of an M. abscessus subspecies massiliense clinical isolate for
attenuated clones. This approach identified five genes within the ESX-4 locus,
which in M. abscessus encodes an ESX-4 type VII secretion system that
exceptionally also includes the ESX conserved EccE component. To confirm the
screening results and to get further insight into the contribution of ESX-4 to M.
abscessus growth and survival in amoebae and macrophages, we generated a deletion
mutant of eccB4 that encodes a core structural element of ESX-4. This mutant was
less efficient at blocking phagosomal acidification than its parental strain.
Importantly, and in contrast to the wild-type strain, it also failed to damage
phagosomes and showed reduced signs of phagosome-to-cytosol contact, as
demonstrated by a combination of cellular and immunological assays. This study
attributes an unexpected and genuine biological role to the underexplored
mycobacterial ESX-4 system and its substrates.
PMID- 29343645
TI - Crystal structure of the mammalian lipopolysaccharide detoxifier.
AB - LPS is a potent bacterial endotoxin that triggers the innate immune system.
Proper recognition of LPS by pattern-recognition receptors requires a full
complement of typically six acyl chains in the lipid portion. Acyloxyacyl
hydrolase (AOAH) is a host enzyme that removes secondary (acyloxyacyl-linked)
fatty acids from LPS, rendering it immunologically inert. This activity is
critical for recovery from immune tolerance that follows Gram-negative infection.
To understand the molecular mechanism of AOAH function, we determined its crystal
structure and its complex with LPS. The substrate's lipid moiety is accommodated
in a large hydrophobic pocket formed by the saposin and catalytic domains with a
secondary acyl chain inserted into a narrow lateral hydrophobic tunnel at the
active site. The enzyme establishes dispensable contacts with the phosphate
groups of LPS but does not interact with its oligosaccharide portion. Proteolytic
processing allows movement of an amphipathic helix possibly involved in substrate
access at membranes.
PMID- 29343646
TI - Role of boundary conditions in determining cell alignment in response to stretch.
AB - The ability of cells to orient in response to mechanical stimuli is essential to
embryonic development, cell migration, mechanotransduction, and other critical
physiologic functions in a range of organs. Endothelial cells, fibroblasts,
mesenchymal stem cells, and osteoblasts all orient perpendicular to an applied
cyclic stretch when plated on stretchable elastic substrates, suggesting a common
underlying mechanism. However, many of these same cells orient parallel to
stretch in vivo and in 3D culture, and a compelling explanation for the different
orientation responses in 2D and 3D has remained elusive. Here, we conducted a
series of experiments designed specifically to test the hypothesis that
differences in strains transverse to the primary loading direction give rise to
the different alignment patterns observed in 2D and 3D cyclic stretch experiments
("strain avoidance"). We found that, in static or low-frequency stretch
conditions, cell alignment in fibroblast-populated collagen gels correlated with
the presence or absence of a restraining boundary condition rather than with
compaction strains. Cyclic stretch could induce perpendicular alignment in 3D
culture but only at frequencies an order of magnitude greater than reported to
induce perpendicular alignment in 2D. We modified a published model of stress
fiber dynamics and were able to reproduce our experimental findings across all
conditions tested as well as published data from 2D cyclic stretch experiments.
These experimental and model results suggest an explanation for the apparently
contradictory alignment responses of cells subjected to cyclic stretch on 2D
membranes and in 3D gels.
PMID- 29343647
TI - On the folding of a structurally complex protein to its metastable active state.
AB - For successful protease inhibition, the reactive center loop (RCL) of the two
domain serine protease inhibitor, alpha1-antitrypsin (alpha1-AT), needs to remain
exposed in a metastable active conformation. The alpha1-AT RCL is sequestered in
a beta-sheet in the stable latent conformation. Thus, to be functional, alpha1-AT
must always fold to a metastable conformation while avoiding folding to a stable
conformation. We explore the structural basis of this choice using folding
simulations of coarse-grained structure-based models of the two alpha1-AT
conformations. Our simulations capture the key features of folding experiments
performed on both conformations. The simulations also show that the free energy
barrier to fold to the latent conformation is much larger than the barrier to
fold to the active conformation. An entropically stabilized on-pathway
intermediate lowers the barrier for folding to the active conformation. In this
intermediate, the RCL is in an exposed configuration, and only one of the two
alpha1-AT domains is folded. In contrast, early conversion of the RCL into a beta
strand increases the coupling between the two alpha1-AT domains in the transition
state and creates a larger barrier for folding to the latent conformation. Thus,
unlike what happens in several proteins, where separate regions promote folding
and function, the structure of the RCL, formed early during folding, determines
both the conformational and the functional fate of alpha1-AT. Further, the short
12-residue RCL modulates the free energy barrier and the folding cooperativity of
the large 370-residue alpha1-AT. Finally, we suggest experiments to test the
predicted folding mechanism for the latent state.
PMID- 29343649
TI - Topological transformations of Hopf solitons in chiral ferromagnets and liquid
crystals.
AB - Liquid crystals are widely known for their facile responses to external fields,
which forms a basis of the modern information display technology. However,
switching of molecular alignment field configurations typically involves
topologically trivial structures, although singular line and point defects often
appear as short-lived transient states. Here, we demonstrate electric and
magnetic switching of nonsingular solitonic structures in chiral nematic and
ferromagnetic liquid crystals. These topological soliton structures are
characterized by Hopf indices, integers corresponding to the numbers of times
that closed-loop-like spatial regions (dubbed "preimages") of two different
single orientations of rod-like molecules or magnetization are linked with each
other. We show that both dielectric and ferromagnetic response of the studied
material systems allow for stabilizing a host of topological solitons with
different Hopf indices. The field transformations during such switching are
continuous when Hopf indices remain unchanged, even when involving
transformations of preimages, but discontinuous otherwise.
PMID- 29343650
TI - Decoder calibration with ultra small current sample set for intracortical brain
machine interface.
AB - OBJECTIVE: Intracortical brain-machine interfaces (iBMIs) aim to restore
efficient communication and movement ability for paralyzed patients. However,
frequent recalibration is required for consistency and reliability, and every
recalibration will require relatively large most current sample set. The aim in
this study is to develop an effective decoder calibration method that can achieve
good performance while minimizing recalibration time. APPROACH: Two rhesus
macaques implanted with intracortical microelectrode arrays were trained
separately on movement and sensory paradigm. Neural signals were recorded to
decode reaching positions or grasping postures. A novel principal component
analysis-based domain adaptation (PDA) method was proposed to recalibrate the
decoder with only ultra small current sample set by taking advantage of large
historical data, and the decoding performance was compared with other three
calibration methods for evaluation. MAIN RESULTS: The PDA method closed the gap
between historical and current data effectively, and made it possible to take
advantage of large historical data for decoder recalibration in current data
decoding. Using only ultra small current sample set (five trials of each
category), the decoder calibrated using the PDA method could achieve much better
and more robust performance in all sessions than using other three calibration
methods in both monkeys. SIGNIFICANCE: (1) By this study, transfer learning
theory was brought into iBMIs decoder calibration for the first time. (2)
Different from most transfer learning studies, the target data in this study were
ultra small sample set and were transferred to the source data. (3) By taking
advantage of historical data, the PDA method was demonstrated to be effective in
reducing recalibration time for both movement paradigm and sensory paradigm,
indicating a viable generalization. By reducing the demand for large current
training data, this new method may facilitate the application of intracortical
brain-machine interfaces in clinical practice.
PMID- 29343648
TI - PAR1 agonists stimulate APC-like endothelial cytoprotection and confer resistance
to thromboinflammatory injury.
AB - Stimulation of protease-activated receptor 1 (PAR1) on endothelium by activated
protein C (APC) is protective in several animal models of disease, and APC has
been used clinically in severe sepsis and wound healing. Clinical use of APC,
however, is limited by its immunogenicity and its anticoagulant activity. We show
that a class of small molecules termed "parmodulins" that act at the cytosolic
face of PAR1 stimulates APC-like cytoprotective signaling in endothelium.
Parmodulins block thrombin generation in response to inflammatory mediators and
inhibit platelet accumulation on endothelium cultured under flow. Evaluation of
the antithrombotic mechanism showed that parmodulins induce cytoprotective
signaling through Gbetagamma, activating a PI3K/Akt pathway and eliciting a
genetic program that includes suppression of NF-kappaB-mediated transcriptional
activation and up-regulation of select cytoprotective transcripts. STC1 is among
the up-regulated transcripts, and knockdown of stanniocalin-1 blocks the
protective effects of both parmodulins and APC. Induction of this signaling
pathway in vivo protects against thromboinflammatory injury in blood vessels.
Small-molecule activation of endothelial cytoprotection through PAR1 represents
an approach for treatment of thromboinflammatory disease and provides proof-of
principle for the strategy of targeting the cytoplasmic surface of GPCRs to
achieve pathway selective signaling.
PMID- 29343651
TI - Determining patient selection tool and response predictor for outpatient 30 mCi
radioiodine ablation dose in non-metastatic differentiated thyroid carcinoma: a
Japanese perspective.
AB - The lack of isolation ward throughout Japan has long been limiting the 131I
radioactive iodine (RAI) ablation for differentiated thyroid cancer (DTC) cases.
The 30 mCi RAI ablation was only recently permitted for outpatient basis.
However, no patient selection tool nor response predictor has been proposed. This
study evaluated factors to find response predictor and determinant for the
suitable patients. The retrospective study reviewed 47 eligible non-metastatic
papillary DTC patients whose had first 30 mCi RAI ablation after total
thyroidectomy. Age, gender, clinical stage, risk category, and pre-ablation serum
thyroglobulin (Tg) level were among covariates analyzed to determine the patient
selection factors; while the thyroid bed uptake on initial whole body scan (WBS)
was later also included in determining RAI ablation response. Thirteen (28%)
patients had a low risk (T1-2) while 23 (49%) and 11 (23%) had an intermediate
(T3) or high risk (T4), respectively. Twenty-five patients were responders, and
22 were non-responders. All factors were similar between responders and non
responders except pre-ablation serum Tg level (p < 0.001). In multivariate
analysis, pre-ablation serum Tg level was the only significant factor for both
patient selection (odd ratio (OR) = 1.52, 95% confidence interval (CI) = 1.13
2.06) and response predictor (OR = 1.48; 95% CI = 1.12-1.95). With the cut-off of
5.4 ng/mL, pre-ablation serum Tg level predicts RAI ablation response with 92%
specificity and 73% sensitivity. Pre-ablation serum Tg level may help patient
selection and predict the response to outpatient 30 mCi RAI ablation among post
total thyroidectomy non-metastatic DTC patients.
PMID- 29343652
TI - Painless Thyroiditis and Fulminant Type 1 Diabetes Mellitus in a Patient Treated
with an Immune Checkpoint Inhibitor, Nivolumab.
AB - The programmed cell death-1 (PD-1) pathway is a novel therapeutic target in
immune checkpoint therapy for cancer. Nivolumab, an anti-PD-1 monoclonal
antibody, blocks PD-1 and can restore anti-cancer immune responses by disrupting
the signal that inhibits T-cell activation. Nivolumab may induce endocrine
related adverse events, including hypophysitis, autoimmune thyroiditis, and type
1 diabetes mellitus. Here we report a 68-year-old female patient with advanced
renal cell carcinoma who was treated with nivolumab. She had positive anti
thyroglobulin antibodies and anti-thyroid peroxidase antibodies with slightly
elevated thyroid-stimulating hormone (9.048 MUU/mL), and was diagnosed as chronic
thyroiditis with subclinical hypothyroidism before nivolumab therapy. She
developed painless thyroiditis after the first cycle of the therapy (Day 14). At
the 7th cycle of nivolumab therapy (Day 98), hyperglycemia (473 mg/dL) was noted,
whereas glycated hemoglobin level was 6.9%. Islet-related autoantibodies were all
negative. The glucagon tolerance test showed complete depletion of insulin. Human
leukocyte antigen typing showed haplotype DRB1*09:01-DQB1*03:03, which was
reported to be closely associated with type 1 diabetes mellitus in Japan.
Fulminant type 1 diabetes mellitus was diagnosed, and she was immediately treated
with multiple daily injections of insulin. Fulminant type 1 diabetes mellitus is
characterized by rapid-onset diabetic ketoacidosis, and negative islet-related
autoantibodies, and was proposed as a novel subtype of non-autoimmune diabetes.
Preceding painless thyroiditis with positive thyroid autoantibodies observed in
the present case, however, raises the possibility that autoimmune mechanisms are
involved in the pathogenesis of nivolumab-induced fulminant type 1 diabetes
mellitus.
PMID- 29343653
TI - Establishment of a Screening System to Identify Novel GATA-2 Transcriptional
Regulators.
AB - Hematopoietic stem cells can self-renew and differentiate into all blood cell
types. The transcription factor GATA-2 is expressed in hematopoietic stem and
progenitor cells and is essential for cell proliferation and differentiation.
Heterozygous germline GATA2 mutations induce GATA-2 deficiency syndrome,
characterized by monocytopenia, a predisposition to myelodysplasia and acute
myeloid leukemia, and a profoundly reduced dendritic cell (DC) population, which
is associated with increased susceptibility to viral infections. Because patients
with GATA-2 deficiency syndrome could retain a wild-type copy of GATA-2, boosting
residual wild-type GATA-2 activity may represent a novel therapeutic strategy for
the disease. Here, we sought to establish a screening system to identify GATA-2
activators using human U937 monocytic cells as a potential model of the DC
progenitor. Enforced GATA-2 expression in U937 cells induces CD205 expression, a
marker of DC differentiation, indicating U937 cells as a surrogate of human
primary DC progenitors. Transient luciferase reporter assays in U937 cells
reveals a high promoter activity of the -0.5 kb GATA-2 hematopoietic-specific
promoter (1S promoter) fused with two tandemly connected GATA-2 +9.9 kb intronic
enhancers. We thus established U937-derived cell lines stably expressing tandem
+9.9 kb/-0.5 kb 1S-luciferase. Importantly, forced GATA-1 expression, a repressor
for GATA-2 expression, in the stable clones caused significant decreases in the
luciferase activities. In conclusion, our system represents a potential tool for
identifying novel regulators of GATA-2, thereby contributing to the development
of novel therapeutic approaches.
PMID- 29343654
TI - Intestinal Epithelial Cell-specific Deletion of alpha-Mannosidase II Ameliorates
Experimental Colitis.
AB - Inflammatory bowel disease (IBD) is a refractory disease of the gastrointestinal
tract that is believed to develop in genetically susceptible individuals.
Glycosylation, a type of post-translational modification, is involved in the
development of a wide range of diseases, including IBD, by modulating the
function of various glycoproteins. To identify novel genes contributing to the
development of IBD, we analyzed single nucleotide polymorphisms (SNPs) of
glycosylation-related genes in IBD patients and identified MAN2A1, encoding alpha
mannosidase II (alpha-MII), as a candidate gene. alpha-MII plays a crucial, but
not exclusive, role in the maturation of N-glycans. We also observed that
intestinal epithelial cells (IECs), which establish the first-line barrier and
regulate gut immunity, selectively expressed alpha-MII with minimal expression of
its isozyme, alpha-mannosidase IIx (alpha-MIIx). This led us to hypothesize that
IEC-intrinsic alpha-MII is implicated in the pathogenesis of IBD. To test this
hypothesis, we generated IEC-specific alpha-MII-deficient (alpha-MIIDeltaIEC)
mice. Although alpha-MII deficiency has been shown to have a minimal effect on N
glycan maturation in most cell types due to the compensation by alpha-MIIx,
ablation of alpha-MII impaired the maturation of N-glycans in IECs. alpha
MIIDeltaIEC mice were less susceptible to dextran sulfate sodium-induced colitis
compared with control littermates. In accordance with this, neutrophil
infiltration in the colonic mucosa was attenuated in alpha-MIIDeltaIEC mice.
Furthermore, gene expression levels of neutrophil-attracting chemokines were
downregulated in the colonic tissue. These results suggest that IEC-intrinsic
alpha-MII promotes intestinal inflammation by facilitating chemokine expression.
We propose SNPs in MAN2A1 as a novel genetic factor for IBD.Key words:
inflammatory bowel disease, alpha-mannosidase II, intestinal epithelial cell, N
glycosylation.
PMID- 29343655
TI - Spatiotemporal alterations of autophagy marker LC3 in rat skin fibroblasts during
wound healing process.
AB - To investigate the possible implications of autophagy, one of the degradation
pathways induced by metabolic stress, in the dynamic reconstructive process of
wound healing, the appearance and changes of punctate structures for microtubule
associated protein 1 light chain 3 (LC3), an autophagosome marker, were examined
in a rat skin wound healing model. Although the ratio of LC3-II/LC3-I in Western
blotting was not evidently changed during the wound healing process, LC3-positive
dots were clearly observed in fibroblasts and myofibroblasts, and occasionally in
macrophages, by immunohistofluorescence microscopy. Some of the LC3-positive dots
were colocalized with Atg16L signal, an isolation membrane marker, and electron
microscopy revealed the presence of typical autophagosomes in fibroblasts near
the margin of the wound. The number of LC3-positive dots per fibroblast increased
during the later period of the proliferation phase, and interestingly, it was
higher in the margin than the center of the wound. It was also high in the
periwound skin area. These results suggest that drastic functional changes in
fibroblasts during wound healing process are accompanied by the alteration of the
autophagy-lysosomal degradation system.
PMID- 29343656
TI - CRISPR-Cas9-mediated generation of obese and diabetic mouse models.
AB - Mouse models of obesity (ob/ob) and diabetes (db/db) in which the leptin (Lep)
and leptin receptor (Lepr) genes have been mutated, respectively, have
contributed to a better understanding of human obesity and type 2 diabetes and to
the prevention, diagnosis, and treatment of these metabolic diseases. In this
study, we report the first CRISPR-Cas9-induced Lep and Lepr knockout (KO) mouse
models by co-microinjection of Cas9 mRNA and sgRNAs that specifically targeted
Lep or Lepr in C57BL/6J embryos. Our newly established Lep and Lepr KO mouse
models showed phenotypic disorders nearly identical to those found in ob/ob and
db/db mice, such as an increase in body weight, hyperglycemia, and hepatic
steatosis. Thus, Cas9-generated Lep and Lepr KO mouse lines will be easier for
genotyping, to maintain the lines, and to use for future obesity and diabetes
research.
PMID- 29343657
TI - Combining Segmented Grey and White Matter Images Improves Voxel-based Morphometry
for the Case of Dilated Lateral Ventricles.
AB - PURPOSE: To evaluate the error in segmented tissue images and to show the
usefulness of the brain image in voxel-based morphometry (VBM) using Statistical
Parametric Mapping (SPM) 12 software and 3D T1-weighted magnetic resonance images
(3D-T1WIs) processed to simulate idiopathic normal pressure hydrocephalus (iNPH).
MATERIALS AND METHODS: VBM analysis was performed on sagittal 3D-T1WIs obtained
in 22 healthy volunteers using a 1.5T MR scanner. Regions of interest for the
lateral ventricles of all subjects were carefully outlined on the original 3D
T1WIs, and two types of simulated 3D-T1WI were also prepared (non-dilated 3D-T1WI
as normal control and dilated 3D-T1WI to simulate iNPH). All simulated 3D-T1WIs
were segmented into gray matter, white matter, and cerebrospinal fluid images,
and normalized to standard space. A brain image was made by adding the gray and
white matter images. After smoothing with a 6-mm isotropic Gaussian kernel, group
comparisons (dilated vs non-dilated) were made for gray and white matter,
cerebrospinal fluid, and brain images using a paired t-test. RESULTS: In
evaluation of tissue volume, estimation error was larger using gray or white
matter images than using the brain image, and estimation errors in gray and white
matter volume change were found for the brain surface. CONCLUSION: To our
knowledge, this is the first VBM study to show the possibility that VBM of gray
and white matter volume on the brain surface may be more affected by individual
differences in the level of dilation of the lateral ventricles than by individual
differences in gray and white matter volumes. We recommend that VBM evaluation in
patients with iNPH should be performed using the brain image rather than the gray
and white matter images.
PMID- 29343658
TI - Differences in Signal Intensity and Enhancement on MR Images of the Perivascular
Spaces in the Basal Ganglia versus Those in White Matter.
AB - PURPOSE: To elucidate differences between the perivascular space (PVS) in the
basal ganglia (BG) versus that found in white matter (WM) using heavily T2
weighted FLAIR (hT2-FL) in terms of 1) signal intensity on non-contrast enhanced
images, and 2) the degree of contrast enhancement by intravenous single dose
administration of gadolinium based contrast agent (IV-SD-GBCA). MATERIALS AND
METHODS: Eight healthy men and 13 patients with suspected endolymphatic hydrops
were included. No subjects had renal insufficiency. All subjects received IV-SD
GBCA. MR cisternography (MRC) and hT2-FL images were obtained prior to and 4 h
after IV-SD-GBCA. The signal intensity of the PVS in the BG, subinsular WM, and
the cerebrospinal fluid (CSF) in Ambient cistern (CSFAC) and CSF in Sylvian
fissure (CSFSyl) was measured as well as that of the thalamus. The signal
intensity ratio (SIR) was calculated by dividing the intensity by that of the
thalamus. We used 5% as a threshold to determine the significance of the
statistical test. RESULTS: In the pre-contrast scan, the SIR of the PVS in WM
(Mean +/- standard deviation, 1.83 +/- 0.46) was significantly higher than that
of the PVS in the BG (1.05 +/- 0.154), CSFSyl (1.03 +/- 0.15) and the CSFAC (0.97
+/- 0.29). There was no significant difference between the SIR of the PVS in the
BG compared to the CSFAC and CSFSyl. For the evaluation of the contrast
enhancement effect, significant enhancement was observed in the PVS in the BG,
the CSFAC and the CSFSyl compared to the pre-contrast scan. No significant
contrast enhancement was observed in the PVS in WM. CONCLUSION: The signal
intensity difference between the PVS in the BG versus WM on pre-contrast images
suggests that the fluid composition might be different between these PVSs. The
difference in the contrast enhancement between the PVSs in the BG versus WM
suggests a difference in drainage function.
PMID- 29343660
TI - MR-guided Focused Ultrasound for Uterine Fibroids: A Preliminary Study of
Relationship between the Treatment Outcomes and Factors of MR Images Including
Elastography.
AB - We evaluated the value of magnetic resonance elastography (MRE) for the
prediction of response to magnetic resonance-guided focused ultrasound (MRgFUS)
for uterine fibroids. Eleven patients were enrolled. A fractional change of >30%
in Symptoms Severity Score (SSS) was defined as a 'substantial symptomatic
improvement' at 12 months after treatment. The fractional stiffness value
reduction in the patients with a substantial improvement in SSS was significantly
higher than that in those without (P = 0.0446).
PMID- 29343659
TI - Cardiac MR Imaging of Hypertrophic Cardiomyopathy: Techniques, Findings, and
Clinical Relevance.
AB - Hypertrophic cardiomyopathy (HCM) is a relatively common myocardial genetic
disease having a wide variety of symptoms and prognoses. The most serious
complications of HCM are sudden cardiac death induced by ventricular arrhythmia
or inappropriate changes in blood pressure, and heart failure. Cardiac MR imaging
is a valuable imaging method for detecting HCM because of its accurate
measurement of wall thickness and myocardial mass without limited view and the
unique ability of late gadolinium enhancement (LGE) to identify myocardial
fibrosis related to the prognosis of HCM. Tagging and T1 or T2 mapping MR imaging
techniques have emerged as quantitative methods for the evaluation of disease
severity. In this review, we introduce the MR imaging techniques applied to HCM
and demonstrate the typical phenotypes and some morphological characteristics of
HCM. In addition, we discuss the clinical relevance of MR imaging for risk
stratification and management of HCM.
PMID- 29343661
TI - Immobilization Technique for High-Resolution MR Imaging of the Testes.
AB - Techniques for testis immobilization can facilitate high-resolution MR imaging
applications for testicular diseases by assuring good positioning of the testis
on small radiofrequency coils and reducing motion artifacts. We tested negative
pressure suction to immobilize the testis of rats during MR image acquisitions.
Suction pressure between -5 and -10 kPa assured good positioning, suppressed
motion artifacts, and allowed the observation of blood vessels and seminiferous
tubules.
PMID- 29343662
TI - Cost-Benefit Performance Simulation of Robot-Assisted Thoracic Surgery As
Required for Financial Viability under the 2016 Revised Reimbursement Paradigm of
the Japanese National Health Insurance System.
AB - PURPOSE: To discuss the cost-benefit performance (CBP) and establish a medical
fee system for robotic-assisted thoracic surgery (RATS) under the Japanese
National Health Insurance System (JNHIS), which is a system not yet firmly
established. METHODS: All management steps for RATS are identical, such as
preoperative and postoperative management. This study examines the CBP based on
medical fees of RATS under the JNHIS introduced in 2016. RESULTS: Robotic
assisted laparoscopic prostatectomy (RALP) and robotic-assisted partial
nephrectomy (RAPN) now receive insurance reimbursement under the category of use
of support devices for endoscopic surgery ($5420 and $3485, respectively). If the
same standard amount were to be applied to RATS, institutions would need to
perform at least 150 or 300 procedures thoracic operation per year to show a
positive CBP ($317 per procedure as same of RALP and $130 per procedure as same
of RAPN, respectively). CONCLUSION: Robotic surgery in some areas receives
insurance reimbursement for its "supportive" use for endoscopic surgery as for
RALP and RAPN. However, at present, it is necessary to perform da Vinci Surgical
System Si (dVSi) surgery at least 150-300 times in a year in a given institution
to prevent a deficit in income.
PMID- 29343663
TI - The Efficacy of VATS and Intrapleural Fibrinolytic Therapy in Parapneumonic
Empyema Treatment.
AB - BACKGROUND: Development of multiloculation-septation is a challenging entity in
empyema patients. In this study, it is aimed to investigate the success rates of
videothoracoscopic deloculation (VATS-D) and intrapleural fibrinolytic (IPFib)
application after tube thoracostomy. METHODS: The study retrospectively examined
the patients diagnosed with empyema with multiloculation and septation between
January 2005 and December 2014. Among these patients, the study included those
who received VATS-D or IPFib therapy. RESULTS: VATS-D (Group 1) was applied to 54
patients and IPFib (Group 2) was applied to 24 patients. The success of both
procedures was evaluated considering the need of decortication in the following
periods. In the VATS-D group, 4 (7.4%) patients required decortication via
thoracotomy where it was 1 (4.1%) patient (p = 0.577) in the IPFib group. The
length of hospital stay was 6.81 +/- 2.55 (4-15) days in Group 1 compared to
14.25 +/- 6.44 (7-27) days in Group 2 (p <0.001). CONCLUSIONS: It was
demonstrated that both of the methods applied in the study have high efficacy and
are preferable methods based on the general conditions of patients. Additionally,
the shorter length of hospital stays in patients received VATS-D was established
as a significant parameter.
PMID- 29343664
TI - The anti-inflammatory action of maropitant in a mouse model of acute
pancreatitis.
AB - The neurokinin 1 receptor (NK1R) plays an important role in the pathogenesis of
acute pancreatitis (AP). Maropitant is an NK1R antagonist that is widely used as
an antiemetic in dogs and cats. In the present study, we investigated the anti
inflammatory action of maropitant in a mouse model of AP. AP was induced in
BALB/c mice by intraperitoneal administration of cerulein, and maropitant was
administered subcutaneously at a dose of 8 mg/kg. We assessed the mRNA expression
levels of NK1R and substance P (SP) in the pancreatic tissue via real-time
reverse transcription polymerase chain reaction. In addition, the effect of
maropitant on plasma amylase, lipase, and interleukin-6 (IL-6) levels was
measured in each mouse. Inflammatory cell infiltration in the pancreas was
assessed by myeloperoxidase (MPO) staining. Our results showed that AP induction
significantly elevated the mRNA expression of SP in the pancreatic tissue.
Treatment with maropitant significantly lowered plasma amylase and IL-6 levels.
In addition, treatment with maropitant inhibited the infiltration of MPO-positive
cells in the pancreas. The present study suggests that maropitant possesses an
anti-inflammatory activity, in addition to its antiemetic action.
PMID- 29343665
TI - Molecular characterization of gliadins of Chinese Spring wheat in relation to
celiac disease elicitors.
AB - The wheat seed storage proteins gliadin and glutenin are encoded by multigenes.
Gliadins are further classified into alpha-, gamma-, delta- and omega-gliadins.
Genes encoding alpha-gliadins belong to a large multigene family, whose members
are located on the homoeologous group 6 chromosomes at the Gli-2 loci. Genes
encoding other gliadins are located on the homoeologous group 1 chromosomes at
the Gli-1 loci. Two-dimensional polyacrylamide gel electrophoresis (2-DE) was
used to characterize and profile the gliadins. The gliadins in aneuploid Chinese
Spring wheat lines were then compared in this study. Gliadin proteins separated
into 70 spots after 2-DE and a total of 10, 10 and 16 spots were encoded on
chromosomes 6A, 6B and 6D, respectively, which suggested that they were alpha
gliadins. Similarly, six, three and seven spots were encoded on chromosomes 1A,
1B and 1D, respectively, which indicated that they were gamma-gliadins. Spots
that could not be assigned to chromosomes were N-terminally sequenced and were
all determined to be alpha-gliadins or gamma-gliadins. The 2-DE profiles showed
that specific alpha-gliadin spots assigned to chromosome 6D were lost in
tetrasomic chromosome 2A lines. Furthermore, western blotting against the Glia
alpha9 peptide, an epitope for celiac disease (CD), suggested that alpha-gliadins
harboring the CD epitope on chromosome 6D were absent in the tetrasomic
chromosome 2A lines. Systematic analysis of alpha-gliadins using 2-DE,
quantitative RT-PCR and genomic PCR revealed that tetrasomic 2A lines carry
deletion of a chromosome segment at the Gli-D2 locus. This structural alteration
at the Gli-D2 locus may provide a genetic resource in breeding programs for the
reduction of CD immunotoxicity.
PMID- 29343666
TI - The C-terminal extension domain of Saccharomyces cerevisiae MrpL32, a homolog of
ribosomal protein L32, functions in trans to support mitochondrial translation.
AB - Mitochondrial ribosomal protein L32 (MrpL32) of Saccharomyces cerevisiae is
homologous to the bacterial L32 ribosomal protein. MrpL32 carries an N-terminal
mitochondrion-targeting sequence (MTS) and is about 60 amino acid residues longer
at the C-terminus. Adding to its function as a leader sequence, the MTS of MrpL32
has been reported to regulate ribosome biogenesis through its processing by m-AAA
protease. However, the function of the C-terminal extension (CE) remains totally
unknown. Therefore, we constructed a series of C-terminally truncated mrpl32
(mrpl32DeltaC) genes and expressed them in a Deltamrpl32 mutant to examine their
function. Interestingly, some MrpL32DeltaC derivatives exhibited temperature
sensitive (ts) growth on medium with non-fermentable carbon sources. Furthermore,
the CE domain of MrpL32, expressed separately from MrpL32DeltaC, could rescue the
ts phenotype of mutants by improving mitochondrial protein synthesis.
PMID- 29343667
TI - Genotypic effects on sugar and by-products of liquid hydrolysates and on
saccharification of acid-insoluble residues from wheat straw.
AB - Wheat straw is one of the major attractive resources for low-cost raw materials
for renewable energy, biofuels and biochemicals. However, like other sources of
lignocellulosic biomass, straw is a heterogeneous material due to its mixed
origin from different tissue and cell types. Here, to examine the genotypic
effects on biorefinery usage of wheat straw, straw obtained from different wheat
cultivars and experimental lines was pretreated with dilute acid. Significant
differences between cultivars were observed in the concentrations of glucose and
toxic by-products of the liquid hydrolysates. A higher content of xylose than
glucose was found in liquid hydrolysates from wheat straw, and the xylose content
appeared to be affected by both environmental and genetic factors. Analysis using
chromosome substitution lines of the common wheat cultivar Chinese Spring showed
that chromosomes 2A and 3A from other wheat cultivars, Hope and Timstein,
significantly increased the xylose content. However, no significant relationship
was observed between the liquid hydrolysate xylose content and the glucose
content obtained from enzymatic saccharification of the acid-insoluble residue.
These results highlight the potential of wheat breeding to improve biomass
related traits in wheat straw.
PMID- 29343668
TI - Configuration of the sugar head of glycolipids in thylakoid membranes.
AB - Glycolipids constitute the majority of membrane components in oxygenic
photosynthetic organisms, whereas they are minor lipids in other organisms. In
cyanobacteria, three glycolipids comprise ~90 mol% of the total lipids in
thylakoid membranes, where photosynthetic electron transport occurs. Among these
glycolipids, 80 mol% are galactolipids (monogalactosyldiacylglycerol and
digalactosyldiacylglycerol). Galactolipids are well conserved in oxygenic
photosynthetic organisms and are believed to be essential for the integrity of
the membrane system. It remains unclear, however, which part(s) of the
galactolipid structure is the key factor for their function, e.g., the sugar
moiety and/or the anomeric configuration. To address this issue, several
bacterial membrane glycolipid synthase genes have been introduced into
cyanobacteria to test for complementation of knocked-out genes involved in
galactolipid biosynthesis. In this review, we summarize recent advances in the
analyses of sugar species and configurations of glycolipids heterologously
synthesized in the thylakoid membrane and discuss their functional importance.
PMID- 29343669
TI - Direct interaction between VRN1 protein and the promoter region of the wheat FT
gene.
AB - The wheat florigen gene Wheat FLOWERING LOCUS T (WFT, which is identical to VRN3)
is an integrator of the vernalization, photoperiod and autonomous pathways in
wheat flowering. Many studies have indicated that VERNALIZATION 1 (VRN1) directly
or indirectly up-regulates WFT expression in leaves. VRN1 encodes an
APETALA1/FRUITFULL-like MADS box transcription factor that is up-regulated by
vernalization and aging, leading to promotion of flowering. In this study, the
VRN1 protein was expressed as a His-Tag fusion protein in Escherichia coli and
used in an electrophoretic mobility shift assay (EMSA). The results from the EMSA
indicated that the VRN1 protein directly binds to the CArG-box in the promoter
region of WFT, suggesting the direct up-regulation of WFT by VRN1 in the leaves
of wheat plants.
PMID- 29343670
TI - Anti-sigma factor-mediated cell surface stress responses in Bacillus subtilis.
AB - Proteins belonging to the sigma factor family in eubacteria initiate
transcription by associating with RNA polymerase. A subfamily, the
extracytoplasmic function (ECF) sigma factors, which form a widely distributed
bacterial signal transduction system comprising a sigma factor and a cognate
membrane-embedded anti-sigma factor, regulates genes in response to stressors
that threaten cell envelope integrity including the cell wall and membrane. The
Gram-positive soil bacterium Bacillus subtilis provides a valuable model for
investigation of the ECF sigma factors. This review focuses on the function and
regulation of ECF sigma factors in B. subtilis, in which anti-sigma factors play
a role in connecting an external stimulus with gene regulation. As representative
examples, the regulon and regulatory mechanism of sigmaW are closely associated
with membrane-active stressors, whereas sigmaM is strongly induced by conditions
that impair peptidoglycan synthesis. These studies demonstrate that the
mechanisms of ECF-dependent signaling are divergent and constitute a multi
layered hierarchy, and provide useful insights into the elucidation of unknown
mechanisms related to ECF sigma factors.
PMID- 29343672
TI - Applying the Seattle Heart Failure Model in the Office Setting in the Era of
Electronic Medical Records.
AB - BACKGROUND: Prediction models such as the Seattle Heart Failure Model (SHFM) can
help guide management of heart failure (HF) patients, but the SHFM has not been
validated in the office environment. This retrospective cohort study assessed the
predictive performance of the SHFM among patients with new or pre-existing HF in
the context of an office visit.Methods and Results:SHFM elements were ascertained
through electronic medical records at an office visit. The primary outcome was
all-cause mortality. A "warranty period" for the baseline SHFM risk estimate was
sought by examining predictive performance over time through a series of landmark
analyses. Discrimination and calibration were estimated according to the proposed
warranty period. Low- and high-risk thresholds were proposed based on the
distribution of SHFM estimates. Among 26,851 HF patients, 14,380 (54%) died over
a mean 4.7-year follow-up period. The SHFM lost predictive performance over time,
with C=0.69 and C<0.65 within 3 and beyond 12 months from baseline respectively.
The diminishing predictive value was attributed to modifiable SHFM elements.
Discrimination (C=0.66) and calibration for 12-month mortality were acceptable. A
low-risk threshold of ~5% mortality risk within 12 months reflects the 10% of HF
patients in the office setting with the lowest risk. CONCLUSIONS: The SHFM has
utility in the office environment.
PMID- 29343671
TI - Development of microsatellite markers for the endangered orchid Calanthe izu
insularis (Orchidaceae).
AB - Microsatellite markers were developed for the endangered orchid Calanthe izu
insularis (Orchidaceae). This species is unique to the Izu Islands in Japan.
Unfortunately, its population size has decreased because of excessive collection
for horticultural purposes. In addition, although natural hybridization between
C. izu-insularis and C. discolor var. discolor has been reported, morphological
differences between C. izu-insularis and the hybridized individuals remain
unclear. Using next-generation sequencing, 11 polymorphic microsatellite markers
were developed. All developed markers could amplify C. aristulifera and nine
markers could amplify C. d. var. discolor, two other orchid species that are also
endangered in Japan. The number of alleles and expected heterozygosity at each
locus were 1-6 (mean, 2.35) and 0.00-0.79 (mean, 0.30), respectively. These
microsatellite markers will help conservation geneticists in their investigation
of the proportion of pure C. izu-insularis individuals in the Izu Islands.
PMID- 29343673
TI - Transcutaneous Exercise Oximetry for Patients With Claudication - A Retrospective
Review of Approximately 5,000 Consecutive Tests Over 15 Years.
AB - BACKGROUND: Exercise transcutaneous oximetry (Ex-tcPO2) is used to argue for the
vascular origin of lower limb pain, especially at the proximal level, where the
diagnosis of peripheral artery disease can be difficult. This study analyzed the
principal indications, mean results, and limitations of Ex-tcPO2, as well as the
relationship between the annual number of Ex-tcPO2 tests and internal iliac
artery (IIA) revascularizations.Methods and Results:Data from our first 15 years'
experience (3,631 patients, 5,080 tests) with Ex-tcPO2 were analyzed
retrospectively using the minimal value of the decrease from rest of oxygen
pressure (DROPmin). We had 99.7% of expected DROPminresults. The proportion of
tests showing isolated proximal unilateral or bilateral ischemia ranged from ~5%
to ~20%. A gradual increase with time was observed in both the annual number of
Ex-tcPO2 tests (from 0 to ~500 per year) and the annual number of IIA
revascularizations performed (from 0 up to 18 per year). At least 85% of patients
(77/91) showed function improvement after IIA revascularization. CONCLUSIONS: Ex
tcPO2 (using DROPmin) provides an objective argument for exercise-induced
ischemia, bilaterally at the distal and/or proximal level. Using Ex-tcPO2 has
improved our diagnostic performance and markedly changed our therapeutic
decisions, specifically for proximal claudication. The increased number of Ex
tcPO2 tests is associated with an increased number of IIA revascularizations,
although a causal relationship was not proven.
PMID- 29343674
TI - A Spontaneous Abdominal Aortic Pseudoaneurysm Treated with N-butyl Cyanoacrylate
and Coil Embolization: A Case Report.
AB - Pseudoaneurysms are vascular spaces vulnerable to pressure, and expansion or
rupture of these spaces may occur during embolization. Here, we describe the case
of a transcatheter embolization of a spontaneous aortic pseudoaneurysm, which
showed gradual expansion during n-butyl cyanoacrylate embolization. This
pseudoaneurysm was successfully embolized with an adjuvant coil.
PMID- 29343676
TI - Editorial Statistics and Best Reviewers Award for 2017.
PMID- 29343675
TI - Diagnostic Accuracy of Quantitative Flow Ratio for Assessing Myocardial Ischemia
in Prior Myocardial Infarction.
AB - BACKGROUND: A novel index of the functional severity of coronary stenosis,
quantitative flow ratio (QFR), may not consider the amount of viable myocardium
in prior myocardial infarction (MI) because QFR is calculated from 3D
quantitative coronary angiography.Methods and Results:We analyzed QFR (fixed-flow
QFR [fQFR] and contrast-flow QFR [cQFR]) and fractional flow reserve (FFR) in
prior-MI-related coronary arteries (n=75) and non-prior-MI-related coronary
arteries (n=75). Both fQFR and cQFR directly correlated with FFR in the prior-MI
related coronary arteries (fQFR: r=0.84, P<0.001; and cQFR: r=0.88, P<0.001) and
the non-prior-MI-related coronary arteries (fQFR: r=0.91, P<0.001; and cQFR:
r=0.94, P<0.001). fQFR was significantly smaller than FFR in the prior-MI-related
coronary arteries (0.73+/-0.14 vs. 0.79+/-0.11, P=0.002), but there was no
significant difference between fQFR and FFR in the non-prior-MI-related coronary
arteries. The value of cQFR minus FFR was significantly lower in the prior-MI
related coronary arteries compared with the non-prior-MI-related coronary
arteries (-0.02+/-0.06 vs. 0.00+/-0.04, P=0.010). The diagnostic accuracy of fQFR
<=0.8 and cQFR <=0.8 for predicting FFR <=0.80 was numerically lower in the prior
MI-related coronary arteries compared with the non-prior-MI-related coronary
arteries (fQFR: 77% vs. 87%; and cQFR: 87% vs. 92%). CONCLUSIONS: When FFR is
used as the gold standard, the accuracy of QFR for assessing the functional
severity of coronary stenosis might be reduced in the prior-MI-related coronary
arteries compared with non-prior-MI-related coronary arteries.
PMID- 29343678
TI - Impact of Anemia on Left Ventricular Reverse Remodeling in Response to
Carvedilol.
PMID- 29343677
TI - Prognostic Factors in Glioblastoma: Is There a Role for Epilepsy?
AB - The prognostic relevance of epilepsy at glioblastoma (GBMs) onset is still under
debate. In this study, we analyzed the value of epilepsy and other prognostic
factors on GBMs survival. We retrospectively analyzed the clinical, radiological,
surgical and histological data in 139 GBMs. Seizures were the presenting symptoms
in 50 patients out of 139 (35.9%). 123 patients (88%) were treated with
craniotomy and tumor resection while 16 (12%) with biopsy. The median overall
survival was 9.9 months from surgery. At univariable Cox regression, the factors
that significantly improved survival were age less than 65 years (P = 0.0015),
focal without impairment of consciousness seizures at presentation (P = 0.043),
complete surgical resection (P < 0.001), pre-operative Karnofsky performance
status (KPS) > 70 (P = 0.015), frontal location (P < 0.001), radiotherapy (XRT)
plus concomitant and adjuvant TMZ (P < 0.001). A multivariable Cox regression
showed that the complete surgical resection (P < 0.0001), age less than 65 years
(P = 0.008), frontal location (P = 0.0001) and XRT adjuvant temozolomide (TMZ) (P
< 0.0001) were independent factors on longer survival. In our series epilepsy at
presentation is not an independent prognostic factor for longer survival in GBM
patients. Only in the subgroup of patients with focal seizures without impairment
of consciousness, epilepsy was associated with an increased significant overall
survival at univariate analysis (P = 0.043). Main independent factors for
relatively favorable GBMs outcome are complete tumor resection plus combined XRT
TMZ, frontal location and patient age below 65 years old.
PMID- 29343679
TI - Ramsay Hunt Syndrome with Multiple Cranial Neuropathy in an Human
Immunodeficiency Virus (HIV) Patient.
AB - BACKGROUND Ramsay Hunt syndrome is a rare otologic complication resulting from
varicella zoster virus reactivation that can present with a myriad of clinical
presentations. Most common being triad of ear pain, vesicles at auricle, and ear
canal with same side facial palsy. CASE REPORT We report a case of a 29-year-old
male with a human immunodeficiency virus (HIV) infection who presented with left
facial palsy, vesicles, pain in the left ear, dysphagia, dizziness, and headache
resulting from multiple cranial nerves involvement such as cranial nerve V, VII,
VIII, IX, and X. CONCLUSIONS This case report raises awareness among general
practitioners to investigate for Ramsay Hunt syndrome in HIV patients presenting
with ear pain with a thorough neurological exam and emphasize on the interplay of
different specialties in managing these patients.
PMID- 29343680
TI - Martrilin-3 (MATN3) Overexpression in Gastric Adenocarcinoma and its Prognostic
Significance.
AB - BACKGROUND The aim of this study was to investigate the expression level of
martrilin-3 (MATN3) in patients with gastric adenocarcinoma (GAC) and to
investigate the prognostic significance of MATN3. MATERIAL AND METHODS Gene
Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data were used to
predict the expression and prognostic value of MATN3 mRNA in GAC patients.
Seventy-six GAC patients had GAC tissue samples and paired adjacent normal tissue
samples collected retrospectively to examine the MATN3 protein expression level
by immunohistochemical staining. Furthermore, Kaplan-Meier univariate and Cox
multivariate analyses were used to verify the correlation between MATN3
expression and clinicopathological parameters of GAC patients and the prognostic
significance of MATN3. RESULTS The GEO and TCGA data predicted that MATN3 mRNA
levels were significantly higher in GAC tissue compared to normal tissue (all
p<0.05). Further survival analyses showed that GAC patients with high mRNA
expression of MATN3 had significantly lower disease-free survival (DFS) and
overall survival (OS) time than those with low mRNA expression of MATN3 (all
p<0.05). Subsequent immunohistochemical staining results confirmed that the MATN3
protein levels in GAC tissues were highly expressed (p=0.000) compared to normal
tissues. In addition, GAC patients with high protein expression of MATN3 had
remarkably decreased OS compared to patients with low protein expression of MATN3
(p=0.000). Univariate and multivariate survival analyses revealed that MATN3 high
expression could be used as an independent predictor of poor prognosis in GAC
patients (all p=0.000). CONCLUSIONS This study confirmed that MATN3 protein was
highly expressed in GAC patients, and MATN3 overexpression could be used as an
independent predictor of poor prognosis in GAC patients.
PMID- 29343681
TI - Oral health in China: from vision to action.
AB - Chinese president Xi Jinping made clear at the National Health and Wellness
Conference that health is the prerequisite for people's all-around development
and a precondition for the sustainable development of China. Oral health is an
indispensable component of overall health in humans. However, the long neglect of
oral health in overall health agendas has made oral diseases an increasing
concern. With this perspective, we described the global challenges of oral
diseases, with an emphasis on the challenges faced by China. We also described
and analyzed the recently released health policies of the Chinese government,
which aim to guide mid-term and long-term oral health promotion in China. More
importantly, we called for specific actions to fulfill the larger goal of oral
health for the nation. The implementation of primordial prevention efforts
against oral diseases, the integration of oral health into the promotion of
overall health, and the management of oral diseases in conjunction with other
chronic non-communicable diseases with shared risk factors were highly
recommended. In addition, we suggested the reform of standard clinical residency
training, the development of domestic manufacturing of dental equipment and
materials, the revitalization traditional Chinese medicine for the prevention and
treatment of oral diseases, and integration of oral health promotion into the
Belt and Road Initiative. We look forward to seeing a joint effort from all
aspects of the society to fulfill the goal of Healthy China 2030 and ensure the
oral health of the nation.
PMID- 29343682
TI - Intermittent C1-Inhibitor Deficiency Associated with Recessive Inheritance:
Functional and Structural Insight.
AB - C1-inhibitor is a serine protease inhibitor (serpin) controlling complement and
contact system activation. Gene mutations result in reduced C1-inhibitor
functional plasma level causing hereditary angioedema, a life-threatening
disorder. Despite a stable defect, the clinical expression of hereditary
angioedema is unpredictable, and the molecular mechanism underlying this
variability remains undisclosed. Here we report functional and structural studies
on the Arg378Cys C1-inhibitor mutant found in a patient presenting reduced C1
inhibitor levels, episodically undergoing normalization. Expression studies
resulted in a drop in mutant C1-innhibitor secretion compared to wild-type.
Notwithstanding, the purified proteins had similar features. Thermal denaturation
experiments showed a comparable denaturation profile, but the mutant thermal
stability decays when tested in conditions reproducing intracellular crowding.Our
findings suggest that once correctly folded, the Arg378Cys C1-inhibitor is
secreted as an active, although quite unstable, monomer. However, it could bear a
folding defect, occasionally promoting protein oligomerization and interfering
with the secretion process, thus accounting for its plasma level variability.
This defect is exacerbated by the nature of the mutation since the acquired
cysteine leads to the formation of non-functional homodimers through inter
molecular disulphide bonding. All the proposed phenomena could be modulated by
specific environmental conditions, rendering this mutant exceptionally vulnerable
to mild stress.
PMID- 29343683
TI - Hypoxia-inducible factor-1alpha is a critical transcription factor for IL-10
producing B cells in autoimmune disease.
AB - Hypoxia-inducible factors (HIFs) are key elements for controlling immune cell
metabolism and functions. While HIFs are known to be involved in T cells and
macrophages activation, their functions in B lymphocytes are poorly defined.
Here, we show that hypoxia-inducible factor-1alpha (HIF-1alpha) contributes to IL
10 production by B cells. HIF-1alpha regulates IL-10 expression, and HIF-1alpha
dependent glycolysis facilitates CD1dhiCD5+ B cells expansion. Mice with B cell
specific deletion of Hif1a have reduced number of IL-10-producing B cells, which
result in exacerbated collagen-induced arthritis and experimental autoimmune
encephalomyelitis. Wild-type CD1dhiCD5+ B cells, but not Hif1a-deficient
CD1dhiCD5+ B cells, protect recipient mice from autoimmune disease, while the
protective function of Hif1a-deficient CD1dhiCD5+ B cells is restored when their
defective IL-10 expression is genetically corrected. Taken together, this study
demonstrates the key function of the hypoxia-associated transcription factor HIF
1alpha in driving IL-10 expression in CD1dhiCD5+ B cells, and in controlling
their protective activity in autoimmune disease.
PMID- 29343684
TI - MAIT cell clonal expansion and TCR repertoire shaping in human volunteers
challenged with Salmonella Paratyphi A.
AB - Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can
detect bacteria-derived metabolites presented on MR1. Here we show, using a
controlled infection of humans with live Salmonella enterica serovar Paratyphi A,
that MAIT cells are activated during infection, an effect maintained even after
antibiotic treatment. At the peak of infection MAIT cell T-cell receptor
(TCR)beta clonotypes that are over-represented prior to infection transiently
contract. Select MAIT cell TCRbeta clonotypes that expand after infection have
stronger TCR-dependent activation than do contracted clonotypes. Our results
demonstrate that host exposure to antigen may drive clonal expansion of MAIT
cells with increased functional avidity, suggesting a role for specific
vaccination strategies to increase the frequency and potency of MAIT cells to
optimize effector function.
PMID- 29343685
TI - The protective role of DOT1L in UV-induced melanomagenesis.
AB - The DOT1L histone H3 lysine 79 (H3K79) methyltransferase plays an oncogenic role
in MLL-rearranged leukemogenesis. Here, we demonstrate that, in contrast to MLL
rearranged leukemia, DOT1L plays a protective role in ultraviolet radiation (UVR)
induced melanoma development. Specifically, the DOT1L gene is located in a
frequently deleted region and undergoes somatic mutation in human melanoma.
Specific mutations functionally compromise DOT1L methyltransferase enzyme
activity leading to reduced H3K79 methylation. Importantly, in the absence of
DOT1L, UVR-induced DNA damage is inefficiently repaired, so that DOT1L loss
promotes melanoma development in mice after exposure to UVR. Mechanistically,
DOT1L facilitates DNA damage repair, with DOT1L-methylated H3K79 involvement in
binding and recruiting XPC to the DNA damage site for nucleotide excision repair
(NER). This study indicates that DOT1L plays a protective role in UVR-induced
melanomagenesis.
PMID- 29343686
TI - Human brain patterns underlying vigilant attention: impact of sleep debt,
circadian phase and attentional engagement.
AB - Sleepiness and cognitive function vary over the 24-h day due to circadian and
sleep-wake-dependent mechanisms. However, the underlying cerebral hallmarks
associated with these variations remain to be fully established. Using functional
magnetic resonance imaging (fMRI), we investigated brain responses associated
with circadian and homeostatic sleep-wake-driven dynamics of subjective
sleepiness throughout day and night. Healthy volunteers regularly performed a
psychomotor vigilance task (PVT) in the MR-scanner during a 40-h sleep
deprivation (high sleep pressure) and a 40-h multiple nap protocol (low sleep
pressure). When sleep deprived, arousal-promoting thalamic activation during
optimal PVT performance paralleled the time course of subjective sleepiness with
peaks at night and troughs on the subsequent day. Conversely, task-related
cortical activation decreased when sleepiness increased as a consequence of
higher sleep debt. Under low sleep pressure, we did not observe any significant
temporal association between PVT-related brain activation and subjective
sleepiness. Thus, a circadian modulation in brain correlates of vigilant
attention was only detectable under high sleep pressure conditions. Our data
indicate that circadian and sleep homeostatic processes impact on vigilant
attention via specific mechanisms; mirrored in a decline of cortical resources
under high sleep pressure, opposed by a subcortical "rescuing" at adverse
circadian times.
PMID- 29343687
TI - Mechanically-sensitive miRNAs bias human mesenchymal stem cell fate via mTOR
signalling.
AB - Mechanotransduction is a strong driver of mesenchymal stem cell (MSC) fate. In
vitro, variations in matrix mechanics invoke changes in MSC proliferation,
migration and differentiation. However, when incorporating MSCs within
injectable, inherently soft hydrogels, this dominance over MSC response
substantially limits our ability to couple the ease of application of hydrogels
with efficiently directed MSC differentiation, especially in the case of bone
generation. Here, we identify differential miRNA expression in response to
varying hydrogel stiffness and RhoA activity. We show that modulation of miR-100
5p and miR-143-3p can be used to bias MSC fate and provide mechanistic insight by
demonstrating convergence on mTOR signalling. By modulating these
mechanosensitive miRNAs, we can enhance osteogenesis in a soft 3D hydrogel. The
outcomes of this study provide new understanding of the mechanisms regulating MSC
mechanotransduction and differentiation, but also a novel strategy with which to
drive MSC fate and significantly impact MSC-based tissue-engineering
applications.
PMID- 29343688
TI - Wee1 inhibitor MK1775 sensitizes KRAS mutated NSCLC cells to sorafenib.
AB - Non-Small-Cell Lung Cancer (NSCLC) is a poorly chemosensitive tumor and targeted
therapies are only used for about 15% of patients where a specific driving and
druggable lesion is observed (EGFR, ALK, ROS). KRAS is one of the most frequently
mutated genes in NSCLC and patients harboring these mutations do not benefit from
specific treatments. Sorafenib, a multi-target tyrosine kinase inhibitor, was
proposed as a potentially active drug in KRAS-mutated NSCLC patients, but
clinical trials results were not conclusive. Here we show that the NSCLC cells'
response to sorafenib depends on the type of KRAS mutation. KRAS G12V cells
respond less to sorafenib than the wild-type counterpart, in vitro and in vivo.
To overcome this resistance, we used high-throughput screening with a siRNA
library directed against 719 human kinases, and Wee1 was selected as a sorafenib
response modulator. Inhibition of Wee1 by its specific inhibitor MK1775 in
combination with sorafenib restored the KRAS mutated cells' response to the multi
target tyrosine kinase inhibitor. This combination of the Wee1 inhibitor with
sorafenib, if confirmed in models with different genetic backgrounds, might be
worth investigating further as a new strategy for KRAS mutated NSCLC.
PMID- 29343689
TI - A novel alpha-conopeptide Eu1.6 inhibits N-type (CaV2.2) calcium channels and
exhibits potent analgesic activity.
AB - We here describe a novel alpha-conopeptide, Eu1.6 from Conus eburneus, which
exhibits strong anti-nociceptive activity by an unexpected mechanism of action.
Unlike other alpha-conopeptides that largely target nicotinic acetylcholine
receptors (nAChRs), Eu1.6 displayed only weak inhibitory activity at the
alpha3beta4 and alpha7 nAChR subtypes and TTX-resistant sodium channels, and no
activity at TTX-sensitive sodium channels in rat dorsal root ganglion (DRG)
neurons, or opiate receptors, VR1, KCNQ1, L- and T-type calcium channels
expressed in HEK293 cells. However, Eu1.6 inhibited high voltage-activated N-type
calcium channel currents in isolated mouse DRG neurons which was independent of
GABAB receptor activation. In HEK293 cells expressing CaV2.2 channels alone,
Eu1.6 reversibly inhibited depolarization-activated Ba2+ currents in a voltage-
and state-dependent manner. Inhibition of CaV2.2 by Eu1.6 was concentration
dependent (IC50 ~1 nM). Significantly, systemic administration of Eu1.6 at doses
of 2.5-5.0 MUg/kg exhibited potent analgesic activities in rat partial sciatic
nerve injury and chronic constriction injury pain models. Furthermore, Eu1.6 had
no significant side-effect on spontaneous locomotor activity, cardiac and
respiratory function, and drug dependence in mice. These findings suggest alpha
conopeptide Eu1.6 is a potent analgesic for the treatment of neuropathic and
chronic pain and opens a novel option for future analgesic drug design.
PMID- 29343691
TI - Use of nanoparticle concentration as a tool to understand the structural
properties of colloids.
AB - Elucidation of the structural properties of colloids is paramount for a
successful formulation. However, the intrinsic dynamism of colloidal systems
makes their characterization a difficult task and, in particular, there is a lack
of physicochemical techniques that can be correlated to their biological
performance. Nanoparticle tracking analysis (NTA) allows measurements of size
distribution and nanoparticle concentration in real time. Its analysis over time
also enables the early detection of physical instability in the systems not
assessed by subtle changes in size distribution. Nanoparticle concentration is a
parameter with the potential to bridge the gap between in vitro characterization
and biological performance of colloids, and therefore should be monitored in
stability studies of formulations. To demonstrate this, we have followed two
systems: extruded liposomes exposed to increasing CHCl3 concentrations, and solid
lipid nanoparticles prepared with decreasing amounts of poloxamer 188. NTA and
dynamic light scattering (DLS) were used to monitor changes in nanoparticle
number and size, and to estimate the number of lipid components per particle. The
results revealed a strong negative correlation between particle size (determined
by DLS) and concentration (assessed by NTA) in diluted samples, which should be
adopted to monitor nanocolloidal stability, especially in drug delivery.
PMID- 29343690
TI - Experimental infection of cattle with Mycobacterium tuberculosis isolates shows
the attenuation of the human tubercle bacillus for cattle.
AB - The Mycobacterium tuberculosis complex (MTBC) is the collective term given to the
group of bacteria that cause tuberculosis (TB) in mammals. It has been reported
that M. tuberculosis H37Rv, a standard reference MTBC strain, is attenuated in
cattle compared to Mycobacterium bovis. However, as M. tuberculosis H37Rv was
isolated in the early 1930s, and genetic variants are known to exist, we sought
to revisit this question of attenuation of M. tuberculosis for cattle by
performing a bovine experimental infection with a recent M. tuberculosis isolate.
Here we report infection of cattle using M. bovis AF2122/97, M. tuberculosis
H37Rv, and M. tuberculosis BTB1558, the latter isolated in 2008 during a TB
surveillance project in Ethiopian cattle. We show that both M. tuberculosis
strains caused reduced gross pathology and histopathology in cattle compared to
M. bovis. Using M. tuberculosis H37Rv and M. bovis AF2122/97 as the extremes in
terms of infection outcome, we used RNA-Seq analysis to explore differences in
the peripheral response to infection as a route to identify biomarkers of
progressive disease in contrast to a more quiescent, latent infection. Our work
shows the attenuation of M. tuberculosis strains for cattle, and emphasizes the
potential of the bovine model as a 'One Health' approach to inform human TB
biomarker development and post-exposure vaccine development.
PMID- 29343692
TI - Symmetric Decomposition of Asymmetric Games.
AB - We introduce new theoretical insights into two-population asymmetric games
allowing for an elegant symmetric decomposition into two single population
symmetric games. Specifically, we show how an asymmetric bimatrix game (A,B) can
be decomposed into its symmetric counterparts by envisioning and investigating
the payoff tables (A and B) that constitute the asymmetric game, as two
independent, single population, symmetric games. We reveal several surprising
formal relationships between an asymmetric two-population game and its symmetric
single population counterparts, which facilitate a convenient analysis of the
original asymmetric game due to the dimensionality reduction of the
decomposition. The main finding reveals that if (x,y) is a Nash equilibrium of an
asymmetric game (A,B), this implies that y is a Nash equilibrium of the symmetric
counterpart game determined by payoff table A, and x is a Nash equilibrium of the
symmetric counterpart game determined by payoff table B. Also the reverse holds
and combinations of Nash equilibria of the counterpart games form Nash equilibria
of the asymmetric game. We illustrate how these formal relationships aid in
identifying and analysing the Nash structure of asymmetric games, by examining
the evolutionary dynamics of the simpler counterpart games in several canonical
examples.
PMID- 29343693
TI - Phantom Acupuncture Induces Placebo Credibility and Vicarious Sensations: A
Parallel fMRI Study of Low Back Pain Patients.
AB - Although acupuncture is an effective therapeutic intervention for pain reduction,
the exact difference between real and sham acupuncture has not been clearly
understood because a somatosensory tactile component is commonly included in the
existing sham acupuncture protocols. In an event-related fMRI experiment, we
implemented a novel form of sham acupuncture, phantom acupuncture, that
reproduces the acupuncture needling procedure without somatosensory tactile
stimulation while maintaining the credibility of the acupuncture treatment
context. Fifty-six non-specific low back pain patients received either real
(REAL) or phantom (PHNT) acupuncture stimulation in a parallel group study. The
REAL group exhibited greater activation in the posterior insula and anterior
cingulate cortex, reflecting the needling-specific components of acupuncture. We
demonstrated that PHNT could be delivered credibly. Interestingly, the PHNT
credible group exhibited bilateral activation in SI/SII and also reported
vicarious acupuncture sensations without needling stimulation. The PHNT group
showed greater activation in the bilateral dorsolateral/ventrolateral prefrontal
cortex (dlPFC/vlPFC). Moreover, the PHNT group exhibited significant pain
reduction, with a significant correlation between the subjective fMRI signal in
the right dlPFC/vlPFC and a score assessing belief in acupuncture effectiveness.
These results support an expectation-related placebo analgesic effect on
subjective pain intensity ratings, possibly mediated by right prefrontal cortex
activity.
PMID- 29343694
TI - Sertraline, Paroxetine, and Chlorpromazine Are Rapidly Acting Anthelmintic Drugs
Capable of Clinical Repurposing.
AB - Parasitic helminths infect over 1 billion people worldwide, while current
treatments rely on a limited arsenal of drugs. To expedite drug discovery, we
screened a small-molecule library of compounds with histories of use in human
clinical trials for anthelmintic activity against the soil nematode
Caenorhabditis elegans. From this screen, we found that the neuromodulatory drugs
sertraline, paroxetine, and chlorpromazine kill C. elegans at multiple life
stages including embryos, developing larvae and gravid adults. These drugs act
rapidly to inhibit C. elegans feeding within minutes of exposure. Sertraline,
paroxetine, and chlorpromazine also decrease motility of adult Trichuris muris
whipworms, prevent hatching and development of Ancylostoma caninum hookworms and
kill Schistosoma mansoni flatworms, three widely divergent parasitic helminth
species. C. elegans mutants with resistance to known anthelmintic drugs such as
ivermectin are equally or more susceptible to these three drugs, suggesting that
they may act on novel targets to kill worms. Sertraline, paroxetine, and
chlorpromazine have long histories of use clinically as antidepressant or
antipsychotic medicines. They may represent new classes of anthelmintic drug that
could be used in combination with existing front-line drugs to boost
effectiveness of anti-parasite treatment as well as offset the development of
parasite drug resistance.
PMID- 29343695
TI - Altered pattern of monocyte differentiation and monocyte-derived TGF-beta1 in
severe asthma.
AB - CD14+ monocytes contain precursors for macrophages and fibrocytes, known to be
involved in regulating airway remodeling in human asthma and distinguishable by
the PM-2K marker. We sought to identify circulating subsets of PM-2K+ macrophage
like cells and evaluate their relationships to lung function, severity and
control status. Circulating PM-2K+ macrophage-like cells and fibrocytes could be
identified and distinguished between normal individuals (N = 152) and asthmatic
subjects (N = 133) using multi-parametric flow cytometry. PM-2K+ macrophage-like
cells were found to be significantly lower in asthmatic subjects, particularly
noted for the CD14-PM-2K+ subset and PM-2K+CCR7-CD86+ cells in subjects with poor
lung function (FEV%/FVC% < 80%) as compared to those of normal subjects and
asthmatics with normal lung function, whereas the frequency of fibrocytes was
higher in asthmatics and the CCR7-CD86+ subset distribution was significantly
different in subjects with varying severity. Moreover, exogenous transforming
growth factor beta 1 (TGF-beta1) was found to inhibit the generation of PM-2K+
macrophage-like cells, but promote the growth of fibrocytes, from CD14+
monocytes, and monocyte-derived TGF-beta1 was found to correlate with the lung
function, severity and control status in asthmatic patients. Collectively,
aberrant differentiation of monocytes into PM-2K+ macrophage-like cell subsets
and fibrocytes, together with increased monocyte-derived TGF-beta1, characterized
patients with severe asthma.
PMID- 29343696
TI - Decoupled in-plane Dipole Resonance Modulated Colorimetric Assay-Based Optical
Ruler for Ultra-Trace Gold (Au) Detection.
AB - Decoupling of different plasmon resonance modes (in-plane, and out-of-plane
dipole and quadrupole resonances) by tuning nanoparticle's size and shape offers
a new field of plasmonics as colorimetric assay-based optical-ruler for ultra
trace sensing. Driven by its low cost, easy to perform and efficient way to
measure trace level (up to 30 ppt in presence of common mining elements in
natural gold ore) abundance, this study develops a highly selective and
ultrasensitive turn-on colorimetric sensor to detect gold-ion from environmental
samples. Different level of gold-ion tracer makes size variable spherical- and
disc-shaped silver nanoparticles when added to a 'growth solution' which results
decoupling of in-plane dipole resonance from in-plane quadrupole and out-of-plane
dipole resonances with a wide range of in-plane dipole plasmon tunability to
generate different colors. This color-coded sensing of gold-ion shows high
selectivity and ultrasensitivity over other metal ions in the ppt level with an
impurity aberration limit of 1 ppm. A plausible explanation explains the possible
role of catalytic gold-ion to initiate unfavorable silver ion (Ag+) reduction by
ascorbic acid to generate silver nanoparticles. Proposed technology has been
applied in real mining sample (Bugunda Gold Deposit, Tajikistan) to detect gold
concentration from ores to find potential application in mining technology.
PMID- 29343697
TI - Effluent and serum protein N-glycosylation is associated with inflammation and
peritoneal membrane transport characteristics in peritoneal dialysis patients.
AB - Mass spectrometric glycomics was used as an innovative approach to identify
biomarkers in serum and dialysate samples from peritoneal dialysis (PD) patients.
PD is a life-saving treatment worldwide applied in more than 100,000 patients
suffering from chronic kidney disease. PD treatment uses the peritoneum as a
natural membrane to exchange waste products from blood to a glucose-based
solution. Daily exposure of the peritoneal membrane to these solutions may cause
complications such as peritonitis, fibrosis and inflammation which, in the long
term, lead to the failure of the treatment. It has been shown in the last years
that protein N-glycosylation is related to inflammatory and fibrotic processes.
Here, by using a recently developed MALDI-TOF-MS method with linkage-specific
sialic acid derivatisation, we showed that alpha2,6-sialylation, especially in
triantennary N-glycans from peritoneal effluents, is associated with critical
clinical outcomes in a prospective cohort of 94 PD patients. Moreover, we found
an association between the levels of presumably immunoglobulin-G-related glycans
as well as galactosylation of diantennary glycans with PD-related complications
such as peritonitis and loss of peritoneal mesothelial cell mass. The observed
glycomic changes point to changes in protein abundance and protein-specific
glycosylation, representing candidate functional biomarkers of PD and associated
complications.
PMID- 29343698
TI - Correlations between mitochondrial DNA haplogroup D5 and chronic hepatitis B
virus infection in Yunnan, China.
AB - Mitochondrial abnormality is frequently reported in individuals with hepatitis B
virus (HBV) infection, but the associated hosts' mitochondrial genetic factors
remain obscure. We hypothesized that mitochondria may affect host susceptibility
to HBV infection. In this study, we aimed to detect the association between
chronic HBV infection and mitochondrial DNA in Chinese from Yunnan, Southwest
China. A total of 272 individuals with chronic HBV infection (CHB), 310 who had
never been infected by HBV (healthy controls, HC) and 278 with a trace of HBV
infection (spontaneously recovered, SR) were analysed for mtDNA sequence
variations and classified into respective haplogroups. Haplogroup frequencies
were compared between HBV infected patients, HCs and SRs. Haplogroup D5 presented
a higher frequency in CHBs than in HCs (P = 0.017, OR = 2.87, 95% confidence
interval [CI] = (1.21-6.81)) and SRs (P = 0.049, OR = 2.90, 95% CI = 1.01-8.35).
The network of haplogroup D5 revealed a distinct distribution pattern between
CHBs and non-CHBs. A trend of higher viral load among CHBs with haplogroup D5 was
observed. Our results indicate the risk potential of mtDNA haplogroup D5 in
chronic HBV infection in Yunnan, China.
PMID- 29343699
TI - Collagen-Binding Hepatocyte Growth Factor (HGF) alone or with a Gelatin-
furfurylamine Hydrogel Enhances Functional Recovery in Mice after Spinal Cord
Injury.
AB - The treatment of spinal cord injury (SCI) is currently a significant challenge.
Hepatocyte growth factor (HGF) is a multipotent neurotrophic and
neuroregenerative factor that can be beneficial for the treatment of SCI.
However, immobilized HGF targeted to extracellular matrix may be more effective
than diffusible, unmodified HGF. In this study, we evaluated the neurorestorative
effects of an engineered HGF with a collagen biding domain (CBD-HGF). CBD-HGF
remained in the spinal cord for 7 days after a single administration, while
unmodified HGF was barely seen at 1 day. When a gelatin-furfurylamine (FA)
hydrogel was applied on damaged spinal cord as a scaffold, CBD-HGF was retained
in gelatin-FA hydrogel for 7 days, whereas HGF had faded by 1 day. A single
administration of CBD-HGF enhanced recovery from spinal cord compression injury
compared with HGF, as determined by motor recovery, and electrophysiological and
immunohistochemical analyses. CBD-HGF alone failed to improve recovery from a
complete transection injury, however CBD-HGF combined with gelatin-FA hydrogel
promoted endogenous repair and recovery more effectively than HGF with hydrogel.
These results suggest that engineered CBD-HGF has superior therapeutic effects
than naive HGF. CBD-HGF combined with hydrogel scaffold may be promising for the
treatment of serious SCI.
PMID- 29343700
TI - Full-field thermal imaging of quasiballistic crosstalk reduction in nanoscale
devices.
AB - Understanding nanoscale thermal transport is of substantial importance for
designing contemporary semiconductor technologies. Heat removal from small
sources is well established to be severely impeded compared to diffusive
predictions due to the ballistic nature of the dominant heat carriers.
Experimental observations are commonly interpreted through a reduction of
effective thermal conductivity, even though most measurements only probe a single
aggregate thermal metric. Here, we employ thermoreflectance thermal imaging to
directly visualise the 2D temperature field produced by localised heat sources on
InGaAs with characteristic widths down to 100 nm. Besides displaying effective
thermal performance reductions up to 50% at the active junctions in agreement
with prior studies, our steady-state thermal images reveal that, remarkably, 1-3
MUm adjacent to submicron devices the crosstalk is actually reduced by up to
fourfold. Submicrosecond transient imaging additionally shows responses to be
faster than conventionally predicted. A possible explanation based on
hydrodynamic heat transport, and some open questions, are discussed.
PMID- 29343701
TI - Alanine mutation of the catalytic sites of Pantothenate Synthetase causes
distinct conformational changes in the ATP binding region.
AB - The enzyme Pantothenate synthetase (PS) represents a potential drug target in
Mycobacterium tuberculosis. Its X-ray crystallographic structure has demonstrated
the significance and importance of conserved active site residues including
His44, His47, Asn69, Gln72, Lys160 and Gln164 in substrate binding and formation
of pantoyl adenylate intermediate. In the current study, molecular mechanism of
decreased affinity of the enzyme for ATP caused by alanine mutations was
investigated using molecular dynamics (MD) simulations and free energy
calculations. A total of seven systems including wild-type + ATP, H44A + ATP,
H47A + ATP, N69A + ATP, Q72A + ATP, K160A + ATP and Q164A + ATP were subjected to
50 ns MD simulations. Docking score, MM-GBSA and interaction profile analysis
showed weak interactions between ATP (substrate) and PS (enzyme) in H47A and
H160A mutants as compared to wild-type, leading to reduced protein catalytic
activity. However, principal component analysis (PCA) and free energy landscape
(FEL) analysis revealed that ATP was strongly bound to the catalytic core of the
wild-type, limiting its movement to form a stable complex as compared to mutants.
The study will give insight about ATP binding to the PS at the atomic level and
will facilitate in designing of non-reactive analogue of pantoyl adenylate which
will act as a specific inhibitor for PS.
PMID- 29343702
TI - Analysis of mitochondrial function in human induced pluripotent stem cells from
patients with mitochondrial diabetes due to the A3243G mutation.
AB - We previously established human induced pluripotent stem (iPS) cells in two
diabetic patients from different families with the mitochondrial A3243G mutation
and isolated isogenic iPS cell clones with either undetectable or high levels of
the mutation in both patients. In the present study, we analyzed the
mitochondrial functions of two mutation-undetectable and two mutation-high clones
in each patient through four methods to assess complex I activity, mitochondrial
membrane potential, mitochondrial respiration, and mitochondrial ATP production.
In the first patient, complex I activity, mitochondrial respiration, and
mitochondrial ATP production were decreased in the mutation-high clones compared
with the mutation-undetectable clones, and mitochondrial membrane potential was
decreased in a mutation-high clone compared with a mutation-undetectable clone.
In the second patient, complex I activity was decreased in one mutation-high
clone compared with the other clones. The other parameters showed no differences
in any clones. In addition, the complex I activity and mitochondrial respiration
of the mutation-undetectable clones from both patients were located in the range
of those of iPS cells from healthy subjects. The present study suggests that the
mitochondrial function of the mutation-undetectable iPS cell clones obtained from
two patients with the A3243G mutation is comparable to the control iPS cells.
PMID- 29343703
TI - A novel microRNA, hsa-miR-6852 differentially regulated by Interleukin-27 induces
necrosis in cervical cancer cells by downregulating the FoxM1 expression.
AB - We have previously demonstrated that Interleukin-27 differentially regulates the
expression of seven novel microRNAs. Here we elucidate the functional
significance of these novel microRNAs. Of the seven microRNAs, over expression of
miRNA-6852 (miR-SX4) mimic induces cell cycle arrest at G2/M phase and induces
necrosis in HEK293 and panel of cervical cancer cells (Human Papilloma Virus
(HPV) infected cell lines; HeLa, CaSki and SiHa cells). To define the mechanism
of the miR-SX4-mediated G2/M arrest, a microarray gene chip array and western
blot analysis were performed. FoxM1, a transcription factor is identified as a
key protein down-regulated by miR-SX4, even though the miR-SX4 does not target
3'UTR of FoxM1. Knock down of FoxM1 using si-RNA demonstrate that FoxM1 silenced
cell induces G2/M cell cycle arrest and necrosis. Our data demonstrated for the
first time that miR-SX4 could be a potent anti-cancer microRNA.
PMID- 29343704
TI - Phosphorylation induced cochaperone unfolding promotes kinase recruitment and
client class-specific Hsp90 phosphorylation.
AB - During the Hsp90-mediated chaperoning of protein kinases, the core components of
the machinery, Hsp90 and the cochaperone Cdc37, recycle between different
phosphorylation states that regulate progression of the chaperone cycle. We show
that Cdc37 phosphorylation at Y298 results in partial unfolding of the C-terminal
domain and the population of folding intermediates. Unfolding facilitates Hsp90
phosphorylation at Y197 by unmasking a phosphopeptide sequence, which serves as a
docking site to recruit non-receptor tyrosine kinases to the chaperone complex
via their SH2 domains. In turn, Hsp90 phosphorylation at Y197 specifically
regulates its interaction with Cdc37 and thus affects the chaperoning of only
protein kinase clients. In summary, we find that by providing client class
specificity, Hsp90 cochaperones such as Cdc37 do not merely assist in client
recruitment but also shape the post-translational modification landscape of Hsp90
in a client class-specific manner.
PMID- 29343705
TI - Nanoscale Structural Modulation and Low-temperature Magnetic Response in Mixed
layer Aurivillius-type Oxides.
AB - Nanoscale structural modulation with different layer numbers in layer-structured
complex oxides of the binary Bi4Ti3O12-BiFeO3 system can give rise to intriguing
phenomena and extraordinary properties, originating from the correlated
interfaces of two different phases with different strain states. In this work, we
studied the nanoscale structural modulation induced by Co-substitution in the
Aurivillius-type oxide of Bi11Fe3Ti6O33 with a unique and naturally occurred
mixed-layer structure. Nanoscale structural evolution via doping occurred from
the phase-modulated structure composed of 4- and 5-layer phases to a homogeneous
4-layer structure was clearly observed utilizing x-ray diffraction and electron
micro-techniques. Significantly, magnetic response for the samples under various
temperatures was recorded and larger magnetic coercive fields (e.g. H c ~ 10 kOe
at 50 K) were found in the phase-modulated samples. Analyses of the x-ray
absorption spectra and magnetic response confirmed that the low-temperature
magnetic behaviour should be intrinsic to the phase-modulated structure inside
the structural transformation region, mainly arising from structural distortions
at the correlated interfaces.
PMID- 29343706
TI - Caloric restriction lowers endocannabinoid tonus and improves cardiac function in
type 2 diabetes.
AB - BACKGROUND/OBJECTIVES: Endocannabinoids (ECs) are associated with obesity and
ectopic fat accumulation, both of which play a role in the development of
cardiovascular disease (CVD) in type 2 diabetes (T2D). The effect of prolonged
caloric restriction on ECs in relation to fat distribution and cardiac function
is still unknown. Therefore, our aim was to investigate this relationship in
obese T2D patients with coronary artery disease (CAD). SUBJECTS/METHODS: In a
prospective intervention study, obese T2D patients with CAD (n = 27) followed a
16 week very low calorie diet (VLCD; 450-1000 kcal/day). Cardiac function and fat
accumulation were assessed with MRI and spectroscopy. Plasma levels of lipid
species, including ECs, were measured using liquid chromatography-mass
spectrometry. RESULTS: VLCD decreased plasma levels of virtually all measured
lipid species of the class of N-acylethanolamines including the EC anandamide
(AEA; -15%, p = 0.016), without decreasing monoacylglycerols including the EC 2
arachidonoylglycerol (2-AG). Baseline plasma AEA levels strongly correlated with
the volume of subcutaneous white adipose tissue (SAT; R2 = 0.44, p < 0.001). VLCD
decreased the volume of SAT (-53%, p < 0.001), visceral white adipose tissue
(VAT) (-52%, p < 0.001), epicardial white adipose tissue (-15%, p < 0.001) and
paracardial white adipose tissue (-28%, p < 0.001). VLCD also decreased hepatic (
86%, p < 0.001) and myocardial (-33%, p < 0.001) fat content. These effects were
accompanied by an increased left ventricular ejection fraction (54.8 +/- 8.7-56.2
+/- 7.9%, p = 0.016). CONCLUSIONS: Caloric restriction in T2D patients with CAD
decreases AEA levels, but not 2-AG levels, which is paralleled by decreased lipid
accumulation in adipose tissue, liver and heart, and improved cardiovascular
function. Interestingly, baseline AEA levels strongly correlated with SAT volume.
We anticipate that dietary interventions are worthwhile strategies in advanced
T2D, and that reduction in AEA may contribute to the improved cardiometabolic
phenotype induced by weight loss.
PMID- 29343707
TI - Sensory neuronal P2RX4 receptors controls BDNF signaling in inflammatory pain.
AB - Chronic inflammatory and neuropathic pains are major public health concerns.
Potential therapeutic targets include the ATP-gated purinergic receptors (P2RX)
that contribute to these pathological types of pain in several different cell
types. The purinergic receptors P2RX2 and P2RX3 are expressed by a specific
subset of dorsal root ganglion neurons and directly shape pain processing by
primary afferents. In contrast the P2RX4 and P2RX7 are mostly expressed in
myeloid cells, where activation of these receptors triggers the release of
various pro-inflammatory molecules. Here, we demonstrate that P2RX4 also controls
calcium influx in mouse dorsal root ganglion neurons. P2RX4 is up-regulated in
pain-processing neurons during long lasting peripheral inflammation and it co
localizes with Brain-Derived Neurotrophic Factor (BDNF). In the dorsal horn of
the spinal cord, BDNF-dependent signaling pathways, phosphorylation of Erk1/2 and
of the GluN1 subunit as well as the down regulation of the co-transporter KCC2,
which are triggered by peripheral inflammation are impaired in P2RX4-deficient
mice. Our results suggest that P2RX4, expressed by sensory neurons, controls
neuronal BDNF release that contributes to hyper-excitability during chronic
inflammatory pain and establish P2RX4 in sensory neurons as a new potential
therapeutic target to treat hyperexcitability during chronic inflammatory pain.
PMID- 29343708
TI - Pteropods counter mechanical damage and dissolution through extensive shell
repair.
AB - The dissolution of the delicate shells of sea butterflies, or pteropods, has
epitomised discussions regarding ecosystem vulnerability to ocean acidification
over the last decade. However, a recent demonstration that the organic coating of
the shell, the periostracum, is effective in inhibiting dissolution suggests that
pteropod shells may not be as susceptible to ocean acidification as previously
thought. Here we use micro-CT technology to show how, despite losing the entire
thickness of the original shell in localised areas, specimens of polar species
Limacina helicina maintain shell integrity by thickening the inner shell wall.
One specimen collected within Fram Strait with a history of mechanical and
dissolution damage generated four times the thickness of the original shell in
repair material. The ability of pteropods to repair and maintain their shells,
despite progressive loss, demonstrates a further resilience of these organisms to
ocean acidification but at a likely metabolic cost.
PMID- 29343709
TI - Experimental and Numerical Investigation on Dragonfly Wing and Body Motion during
Voluntary Take-off.
AB - We present a detailed analysis of the voluntary take-off procedure of a
dragonfly. The motions of the body and wings are recorded using two high-speed
cameras at Beihang University. The experimental results show that the dragonfly
becomes airborne after approximately one wingbeat and then leaves the ground.
During this process, the maximum vertical acceleration could reach 20 m/s2.
Evidence also shows that acceleration is generated only by the aerodynamic force
induced by the flapping of wings. The dragonfly voluntary take-off procedure is
divided into four phases with distinctive features. The variation in phase
difference between the forewing and hindwing and angle of attack in the down
stroke are calculated to explain the different features of the four phases. In
terms of the key parameters of flapping, the phase difference increases from
approximately 0 to 110 degrees; the angle of attack in down-stroke reaches the
maximum at first and then decreases in the following take-off procedure. Due to
experimental limitations, 2-D simulations are conducted using the immersed
boundary method. The results indicate that the phase difference and the angle of
attack are highly correlated with the unsteady fluid field around the dragonfly's
wings and body, which determines the generation of aerodynamic forces.
PMID- 29343711
TI - Silver Nanoparticles in the Water Environment in Malaysia: Inspection,
characterization, removal, modeling, and future perspective.
AB - The current status of silver nanoparticles (AgNPs) in the water environment in
Malaysia was examined and reported. For inspection, two rivers and two sewage
treatment plants (STPs) were selected. Two activated carbons derived from oil
palm (ACfOPS) and coconut (ACfCS) shells were proposed as the adsorbent to remove
AgNPs. It was found that the concentrations of AgNPs in the rivers and STPs are
in the ranges of 0.13 to 10.16 mg L-1 and 0.13 to 20.02 mg L-1, respectively,
with the highest concentration measured in July. ACfOPS and ACfCS removed up to
99.6 and 99.9% of AgNPs, respectively, from the water. The interaction mechanism
between AgNPs and the activated carbon surface employed in this work was mainly
the electrostatic force interaction via binding Ag+ with O- presented in the
activated carbon to form AgO. Fifteen kinetic models were compared statistically
to describe the removal of AgNPs. It was found that the experimental adsorption
data can be best described using the mixed 1,2-order model. Therefore, this model
has the potential to be a candidate for a general model to describe AgNPs
adsorption using numerous materials, its validation of which has been confirmed
with other material data from previous works.
PMID- 29343710
TI - Phenotypic diversity identified by cardiac magnetic resonance in a large
hypertrophic cardiomyopathy family with a single MYH7 mutation.
AB - Limited data is available on phenotypic variations with the same genotype in
hypertrophic cardiomyopathy (HCM). The present study aims to explore the
relationship between genotype and phenotype characterized by cardiovascular
magnetic resonance (CMR) in a large Chinese family. A proband diagnosed with HCM
from a multigenerational family underwent next-generation sequencing based on a
custom sureSelect panel, including 117 candidate pathogenic genes associated with
cardiomyopathies. All genetic results were confirmed by the Sanger sequencing
method. All confirmed mutation carriers underwent CMR exam and myocardial tissue
characterization using T1 mapping and late gadolinium enhancement (LGE) on a 3T
scanner (Siemens Trio, Gemany). After clinical and genetic screening of 36
(including the proband) members of a large Chinese family, nineteen family
members are determined to carry the single p.T1377M (c.4130C>T) mutation in the
MYH7 gene. Of these 19 mutation carriers, eight are diagnosed with HCM, one was
considered as borderline affected and ten are not clinically or phenotypically
affected. Different HCM phenotypes are present in the nine affected individuals
in this family. In addition, we have found different tissue characteristics
assessed by T1 mapping and LGE in these individuals. We describe a family that
demonstrates the diverse HCM phenotypes associated with a single MYH7 mutation.
PMID- 29343713
TI - Atmospheric CO2 effect on stable carbon isotope composition of terrestrial fossil
archives.
AB - The 13C/12C ratio of C3 plant matter is thought to be controlled by the isotopic
composition of atmospheric CO2 and stomatal response to environmental conditions,
particularly mean annual precipitation (MAP). The effect of CO2 concentration on
13C/12C ratios is currently debated, yet crucial to reconstructing ancient
environments and quantifying the carbon cycle. Here we compare high-resolution
ice core measurements of atmospheric CO2 with fossil plant and faunal isotope
records. We show the effect of pCO2 during the last deglaciation is stronger for
gymnosperms (-1.4 +/- 1.20/00) than angiosperms/fauna (-0.5 +/- 1.50/00), while
the contributions from changing MAP are -0.3 +/- 0.60/00 and -0.4 +/- 0.40/00,
respectively. Previous studies have assumed that plant 13C/12C ratios are mostly
determined by MAP, an assumption which is sometimes incorrect in geological time.
Atmospheric effects must be taken into account when interpreting terrestrial
stable carbon isotopes, with important implications for past environments and
climates, and understanding plant responses to climate change.
PMID- 29343712
TI - Zika virus infection in pregnant rhesus macaques causes placental dysfunction and
immunopathology.
AB - Zika virus (ZIKV) infection during pregnancy leads to an increased risk of fetal
growth restriction and fetal central nervous system malformations, which are
outcomes broadly referred to as the Congenital Zika Syndrome (CZS). Here we
infect pregnant rhesus macaques and investigate the impact of persistent ZIKV
infection on uteroplacental pathology, blood flow, and fetal growth and
development. Despite seemingly normal fetal growth and persistent fetal-placenta
maternal infection, advanced non-invasive in vivo imaging studies reveal dramatic
effects on placental oxygen reserve accompanied by significantly decreased oxygen
permeability of the placental villi. The observation of abnormal oxygen transport
within the placenta appears to be a consequence of uterine vasculitis and
placental villous damage in ZIKV cases. In addition, we demonstrate a robust
maternal-placental-fetal inflammatory response following ZIKV infection. This
animal model reveals a potential relationship between ZIKV infection and
uteroplacental pathology that appears to affect oxygen delivery to the fetus
during development.
PMID- 29343714
TI - Endothelial nitric oxide synthase overexpressing human early outgrowth cells
inhibit coronary artery smooth muscle cell migration through paracrine functions.
AB - Cells mobilized from the bone marrow can contribute to endothelial regeneration
and repair. Nevertheless, cardiovascular diseases are associated with diminished
numbers and function of these cells, attenuating their healing potential. Gene
transfer of endothelial nitric oxide synthase (eNOS) can restore the activity of
circulating cells. Furthermore, estrogen accelerates the reendothelialization
capacity of early outgrowth cells (EOCs). We hypothesized that overexpressing
eNOS alone or in combination with estrogen stimulation in EOCs would potentiate
the beneficial effects of these cells in regulating smooth muscle cell (SMC)
function. Native human EOCs did not have any effect on human coronary artery SMC
(hCASMC) proliferation or migration. Transfecting EOCs with a human eNOS plasmid
and/or stimulating with 17beta-estradiol (E2) increased NO production 3-fold and
enhanced EOC survival. Moreover, in co-culture studies, eNOS overexpressing or E2
stimulated EOCs reduced hCASMC migration (by 23% and 56% respectively), vs.
control EOCs. These effects do not implicate ERK1/2 or focal adhesion kinases.
Nevertheless, NOS-EOCs had no effect on hCASMC proliferation. These results
suggest that overexpressing or activating eNOS in EOCs increases their survival
and enhances their capacity to regulate SMC migration through paracrine effects.
These data elucidate how eNOS overexpression or activation in EOCs can prevent
vascular remodeling.
PMID- 29343715
TI - Effects of straw application on nitrate leaching in fields in the Yellow River
irrigation zone of Ningxia, China.
AB - A five-year field experiment was conducted to investigate the effects of straw
application on nitrate leaching loss. Treatments included soil that was not
treated (control), soil treated with straw at a low rate (4,500 kg ha-2, T1) and
soil treated with straw at a high rate (9,000 kg ha-2, T2). Nitrate-nitrogen
leaching in the 10, 20, 30, 60, and 90 cm soil layers was measured using the
resin-core method. The results indicated that straw application could reduce soil
nitrate leaching losses in the 0-30 cm layer. In this layer, the nitrate leaching
values for T1 (13.76 kg ha-2) and T2 (13.74 kg ha-2) were both significantly
lower than those of the control (15.76 kg ha-2) (P < 0.05); the soil nitrate
leaching losses decreased by 12.71% and 12.84% for those two treatments,
respectively. However, no significant differences in losses were observed (P >
0.05) between T1 and T2. The effects of straw application were apparent only in
the ploughing layer (30 cm-depth soil layer). In the deeper layers (60 and 90
cm), no significant differences were observed between the treatments and the
control, and the same results were observed in the topsoil layers (10 and 20 cm).
PMID- 29343716
TI - Expression of the methionine sulfoxide reductase lost during evolution extends
Drosophila lifespan in a methionine-dependent manner.
AB - Accumulation of oxidized amino acids, including methionine, has been implicated
in aging. The ability to reduce one of the products of methionine oxidation, free
methionine-R-sulfoxide (Met-R-SO), is widespread in microorganisms, but during
evolution this function, conferred by the enzyme fRMsr, was lost in metazoa. We
examined whether restoration of the fRMsr function in an animal can alleviate the
consequences of methionine oxidation. Ectopic expression of yeast fRMsr supported
the ability of Drosophila to catalyze free Met-R-SO reduction without affecting
fecundity, food consumption, and response to starvation. fRMsr expression also
increased resistance to oxidative stress. Moreover, it extended lifespan of flies
in a methionine-dependent manner. Thus, expression of an oxidoreductase lost
during evolution can enhance metabolic and redox functions and lead to an
increase in lifespan in an animal model. More broadly, our study exposes the
potential of a combination of genetic and nutritional strategies in lifespan
control.
PMID- 29343717
TI - The role of NFkappaB in spheroid formation of human breast cancer cells cultured
on the Random Positioning Machine.
AB - Human MCF-7 breast cancer cells were exposed to a Random Positioning Machine
(RPM). After 24 hours (h) the cells grew either adherently within a monolayer
(AD) or within multicellular spheroids (MCS). AD and MCS populations were
separately harvested, their cellular differences were determined performing qPCR
on genes, which were differently expressed in AD and MCS cells. Gene array
technology was applied to detect RPM-sensitive genes in MCF-7 cells after 24 h.
Furthermore, the capability to form multicellular spheroids in vitro was compared
with the intracellular distribution of NF-kappaB (NFkappaB) p65. NFkappaB was
equally distributed in static control cells, but predominantly localized in the
cytoplasm in AD cells and nucleus in MCS cells exposed to the RPM. Gene array
analyses revealed a more than 2-fold change of only 23 genes including some whose
products are affected by oxygen levels or regulate glycolysis. Significant
upregulations of the mRNAs of enzymes degrading heme, of ANXA1, ANXA2, CTGF, CAV2
and ICAM1, as well as of FAS, Casp8, BAX, p53, CYC1 and PARP1 were observed in
MCS cells as compared with 1g-control and AD cells. An interaction analysis of 47
investigated genes suggested that HMOX-1 and NFkappaB variants are activated,
when multicellular spheroids are formed.
PMID- 29343718
TI - The bacterial Type III toxin-antitoxin system, ToxIN, is a dynamic protein-RNA
complex with stability-dependent antiviral abortive infection activity.
AB - Bacteria have evolved numerous defense systems to protect themselves from viral
(bacteriophage) infection. The ToxIN system of Pectobacterium atrosepticum is a
Type III toxin-antitoxin complex and "altruistic suicide" anti-phage system,
which kills phage-infected cells through the release of a ribonuclease toxin,
ToxN. ToxN is counteracted by a co-transcribed antitoxic RNA pseudoknot, ToxI,
which self-assembles with ToxN into an inactive 3 ToxI:3 ToxN complex in vitro.
However it is not known whether this complex is predominant in vivo, or how the
complex is disassembled following infection to trigger a lethal, "altruistic"
response. In this study, we characterise ToxI turnover and folding, and explore
the link between complex stability and anti-phage activity, with a view to
understanding events that lead to ToxN-mediated suicide following phage
infection. We present evidence that ToxN constantly cleaves fresh ToxI in vivo
rather than staying associated with pre-processed antitoxin, and that the ToxI
antitoxin can partially fold spontaneously using conserved nucleotides. We also
show that reducing the stability of the ToxIN complex can increase the strength
of the antiviral response in a phage-dependent manner. Based on this information,
we propose a revised model for ToxN inhibition, complex assembly and activation
by infecting bacteriophage.
PMID- 29343719
TI - The Significant Role of c-Abl Kinase in Barrier Altering Agonists-mediated
Cytoskeletal Biomechanics.
AB - Exploration of human pulmonary artery endothelial cell (EC) as a prototypical
biomechanical system has important pathophysiologic relevance because this cell
type plays a key role in the development of a wide variety of clinical
conditions. The complex hierarchical organization ranging from the molecular
scale up to the cellular level has an intimate and intricate relationship to the
barrier function between lung tissue and blood. To understand the innate molecule
cell-tissue relationship across varied length-scales, the functional role of c
Abl kinase in the cytoskeletal nano-biomechanics of ECs in response to barrier
altering agonists was investigated using atomic force microscopy. Concurrently,
the spatially specific arrangement of cytoskeleton structure and dynamic
distribution of critical proteins were examined using scanning electron
microscopy and immunofluorescence. Reduction in c-Abl expression by siRNA
attenuates both thrombin- and sphingosine 1-phosphate (S1P)-mediated structural
changes in ECs, specifically spatially-defined changes in elastic modulus and
distribution of critical proteins. These results indicate that c-Abl kinase is an
important determinant of cortical actin-based cytoskeletal rearrangement. Our
findings directly bridge the gap between kinase activity, structural complexity,
and functional connectivity across varied length-scales, and suggest that
manipulation of c-Abl kinase activity may be a potential target for the treatment
of pulmonary barrier disorders.
PMID- 29343720
TI - Associations between VDR Gene Polymorphisms and Osteoporosis Risk and Bone
Mineral Density in Postmenopausal Women: A systematic review and Meta-Analysis.
AB - Results on the relationships between vitamin D receptor (VDR) gene polymorphisms
and postmenopausal osteoporosis (PMOP) susceptibility and bone mineral density
(BMD) are conflicting. The aim of the study is to identify more eligible studies
that calculated pooled OR and WMD with 95% CI to assess their associations.
Overall, there were significant correlations between VDR ApaI, VDR FokI and PMOP
susceptibility. Subgroup analysis showed that VDR ApaI polymorphism significantly
decreased the osteoporosis risk in Caucasian postmenopausal women. In Asian
populations, VDR BsmI and VDR FokI were associated with an increased risk of
PMOP. As to the associations between VDR polymorphisms and BMD, Caucasian PMOP
women carrying the ApaI aa genotype were at risk of high BMD in femoral neck, and
low femoral neck BMD was observed in Caucasian PMOP women with FokI Ff genotype.
PMOP women with the Cdx2 GA genotype had a lower lumbar spine BMD in overall and
Caucasian populations compared with PMOP women with GG genotype. Different VDR
gene polymorphisms have different impacts on PMOP risk and BMD.
PMID- 29343721
TI - ?133p53 isoform promotes tumour invasion and metastasis via interleukin-6
activation of JAK-STAT and RhoA-ROCK signalling.
AB - ?122p53 mice (a model of ?133p53 isoform) are tumour-prone, have extensive
inflammation and elevated serum IL-6. To investigate the role of IL-6 we crossed
?122p53 mice with IL-6 null mice. Here we show that loss of IL-6 reduced JAK-STAT
signalling, tumour incidence and metastasis. We also show that ?122p53 activates
RhoA-ROCK signalling leading to tumour cell invasion, which is IL-6-dependent and
can be reduced by inhibition of JAK-STAT and RhoA-ROCK pathways. Similarly, we
show that Delta133p53 activates these pathways, resulting in invasive and
migratory phenotypes in colorectal cancer cells. Gene expression analysis of
colorectal tumours showed enrichment of GPCR signalling associated with ?133TP53
mRNA. Patients with elevated ?133TP53 mRNA levels had a shorter disease-free
survival. Our results suggest that ?133p53 promotes tumour invasion by activation
of the JAK-STAT and RhoA-ROCK pathways, and that patients whose tumours have high
?133TP53 may benefit from therapies targeting these pathways.
PMID- 29343722
TI - Multiplex glycan bead array for high throughput and high content analyses of
glycan binding proteins.
AB - Glycan-binding proteins (GBPs) play critical roles in diverse cellular functions
such as cell adhesion, signal transduction and immune response. Studies of the
interaction between GBPs and glycans have been hampered by the availability of
high throughput and high-content technologies. Here we report multiplex glycan
bead array (MGBA) that allows simultaneous analyses of 384 samples and up to 500
glycans in a single assay. The specificity, sensitivity and reproducibility of
MGBA are evaluated using 39 plant lectins, 13 recombinant anti-glycan antibodies,
and mammalian GBPs. We demonstrate the utility of this platform by the analyses
of natural anti-glycan IgM and IgG antibodies in 961 human serum samples and the
discovery of anti-glycan antibody biomarkers for ovarian cancer. Our data
indicate that the MGBA platform is particularly suited for large population-based
studies that require the analyses of large numbers of samples and glycans.
PMID- 29343723
TI - Pharmacological targeting of BET proteins attenuates radiation-induced lung
fibrosis.
AB - Radiation-induced lung injury has restricted radiotherapy for thoracic cancer.
The purpose of this study was to investigate the radioprotective effects of
bromodomain and extra terminal (BET) inhibitor JQ1 in a murine model of pulmonary
damage. Chest computed tomography (CT) was performed in a rat model after 20 Gy
radiation of the right thorax. And histological evaluation and protein
expressions of irradiated tissue were analyzed to confirm the potential anti
fibrosis effect of JQ1 and its underlying mechanisms. Moreover, colony formation
assays were used to explore the effects of JQ1 on esophageal cancer Eca109 and
breast cancer MCF7. JQ1 attenuated radiologic and histologic presentations of
radiation-induced fibrosis, inflammatory reaction and pulmonary structural
changes and the increase of Hounsfield units (HU) density and hydroxyproline
content after radiation. Additionally, JQ1 suppressed BRD4, c-MYC, Collagen I,
TGF-beta, p-NF-kappaB p65, p-Smad2 and p-Smad3 expressions after irradiation,
repressed proliferation and transdifferentiation of lung fibroblasts, and
impaired clonogenic survival of thoracic cancer cells. Collectively, our study
demonstrated for the first time that BET Bromodomain inhibitor JQ1 protected
normal lung tissue after radiation, and exerted a radiosensitizing effect in
thoracic cancer cells.
PMID- 29343724
TI - The UV filtering potential of drop-casted layers of frustules of three diatom
species.
AB - Diatoms are in focus as biological materials for a range of photonic
applications. Many of these applications would require embedding a multitude of
diatoms in a matrix (e.g. paint, creme or lacquer); however, most studies on the
photonic and spectral properties of diatoms frustules (silica walls) have been
carried out on single cells. In this study, for the first time, we test the
spectral properties of layers of frustules of three diatom species (Coscinodiscus
granii, Thalassiosira punctifera and Thalassiosira pseudonana), with special
focus on transmission and reflectance in the UV range. The transmittance
efficiency in the UV A and B range was: T. pseudonana (56-59%) >C. granii (53
54%) >T. punctifera (18-21%) for the rinsed frustules. To investigate the
underlying cause of these differences, we performed X-ray scattering analysis,
measurement of layer thickness and microscopic determination of frustule
nanostructures. We further tested dried intact cells in the same experimental
setup. Based on these data we discuss the relative importance of crystal
structure properties, nanostructure and quantity of material on the spectral
properties of diatom layers. Characterization of the UV protection performance of
layers of diatom frustules is of central relevance for their potential use as
innovative bio-based UV filters.
PMID- 29343726
TI - Remarkably High Hole Mobility Metal-Oxide Thin-Film Transistors.
AB - High performance p-type thin-film transistor (p-TFT) was realized by a simple
process of reactive sputtering from a tin (Sn) target under oxygen ambient, where
remarkably high field-effect mobility (MU FE ) of 7.6 cm2/Vs, 140 mV/dec
subthreshold slope, and 3 * 104 on-current/off-current were measured. In sharp
contrast, the SnO formed by direct sputtering from a SnO target showed much
degraded MU FE , because of the limited low process temperature of SnO and
sputtering damage. From the first principle quantum-mechanical calculation, the
high hole MU FE of SnO p-TFT is due to its considerably unique merit of the small
effective mass and single hole band without the heavy hole band. The high
performance p-TFTs are the enabling technology for future ultra-low-power
complementary-logic circuits on display and three-dimensional brain-mimicking
integrated circuits.
PMID- 29343725
TI - The phosphatase PPM1A controls monocyte-to-macrophage differentiation.
AB - Differentiation of circulating monocytes into tissue-bound or tissue-resident
macrophages is a critical regulatory process affecting host defense and
inflammation. However, the regulatory signaling pathways that control the
differentiation of monocytes into specific and distinct functional macrophage
subsets are poorly understood. Herein, we demonstrate that monocyte-to-macrophage
differentiation is controlled by the Protein Phosphatase, Mg2+/Mn2+-dependent 1A
(PPM1A). Genetic manipulation experiments demonstrated that overexpression of
PPM1A attenuated the macrophage differentiation program, while knockdown of PPM1A
expression accelerated the ability of monocytes to differentiate into
macrophages. We identify imiquimod and Pam3CSK4 as two Toll-like receptor
agonists that induce PPM1A expression, and show that increased expression of
PPM1A at the onset of differentiation impairs cellular adherence, reduces
expression of inflammatory (M1) macrophage-specific markers, and inhibits the
production of inflammatory cytokines. Our findings reveal PPM1A as a negative
threshold regulator of M1-type monocyte-to-macrophage differentiation,
establishing it as a key phosphatase that orchestrates this program.
PMID- 29343727
TI - PredCRP: predicting and analysing the regulatory roles of CRP from its binding
sites in Escherichia coli.
AB - Cyclic AMP receptor protein (CRP), a global regulator in Escherichia coli,
regulates more than 180 genes via two roles: activation and repression. Few
methods are available for predicting the regulatory roles from the binding sites
of transcription factors. This work proposes an accurate method PredCRP to derive
an optimised model (named PredCRP-model) and a set of four interpretable rules
(named PredCRP-ruleset) for predicting and analysing the regulatory roles of CRP
from sequences of CRP-binding sites. A dataset consisting of 169 CRP-binding
sites with regulatory roles strongly supported by evidence was compiled. The
PredCRP-model, using 12 informative features of CRP-binding sites, and
cooperating with a support vector machine achieved a training and test accuracy
of 0.98 and 0.93, respectively. PredCRP-ruleset has two activation rules and two
repression rules derived using the 12 features and the decision tree method C4.5.
This work further screened and identified 23 previously unobserved regulatory
interactions in Escherichia coli. Using quantitative PCR for validation, PredCRP
model and PredCRP-ruleset achieved a test accuracy of 0.96 (=22/23) and 0.91
(=21/23), respectively. The proposed method is suitable for designing predictors
for regulatory roles of all global regulators in Escherichia coli. PredCRP can be
accessed at https://github.com/NctuICLab/PredCRP .
PMID- 29343728
TI - Oxidation of SQSTM1/p62 mediates the link between redox state and protein
homeostasis.
AB - Cellular homoeostatic pathways such as macroautophagy (hereinafter autophagy) are
regulated by basic mechanisms that are conserved throughout the eukaryotic
kingdom. However, it remains poorly understood how these mechanisms further
evolved in higher organisms. Here we describe a modification in the autophagy
pathway in vertebrates, which promotes its activity in response to oxidative
stress. We have identified two oxidation-sensitive cysteine residues in a
prototypic autophagy receptor SQSTM1/p62, which allow activation of pro-survival
autophagy in stress conditions. The Drosophila p62 homologue, Ref(2)P, lacks
these oxidation-sensitive cysteine residues and their introduction into the
protein increases protein turnover and stress resistance of flies, whereas
perturbation of p62 oxidation in humans may result in age-related pathology. We
propose that the redox-sensitivity of p62 may have evolved in vertebrates as a
mechanism that allows activation of autophagy in response to oxidative stress to
maintain cellular homoeostasis and increase cell survival.
PMID- 29343730
TI - First estimates of Greenland shark (Somniosus microcephalus) local abundances in
Arctic waters.
AB - Baited remote underwater video cameras were deployed in the Eastern Canadian
Arctic, for the purpose of estimating local densities of the long-lived Greenland
shark within five deep-water, data-poor regions of interest for fisheries
development and marine conservation in Nunavut, Canada. A total of 31 camera
deployments occurred between July-September in 2015 and 2016 during joint
exploratory fishing and scientific cruises. Greenland sharks appeared at 80% of
deployments. A total of 142 individuals were identified and no individuals were
observed in more than one deployment. Estimates of Greenland shark abundance and
biomass were calculated from averaged times of first arrival, video-derived
swimming speed and length data, and local current speed estimates. Density
estimates varied 1-15 fold among regions; being highest in warmer (>0 degrees
C), deeper areas and lowest in shallow, sub-zero temperature regions. These
baited camera results illustrate the ubiquity of this elusive species and suggest
that Nunavut's Lancaster Sound eco-zone may be of particular importance for
Greenland shark, a potentially vulnerable Arctic species.
PMID- 29343729
TI - Drug self-assembly for synthesis of highly-loaded antimicrobial drug-silica
particles.
AB - Antimicrobial drug release from biomaterials for orthopedic repair and dental
restorations can prevent biofilm growth and caries formation. Carriers for drug
incorporation would benefit from long-term drug storage, controlled release, and
structural stability. Mesoporous silica, synthesized through a co-assembly of
silica and surfactant template, is an ideal drug encapsulation scaffold that
maintains structural integrity upon release. However, conventional loading of
drug within meso-silica pores via concentration-gradient diffusion limits the
overall payload, concentration uniformity, and drug release control. Herein we
demonstrate the co-assembly of an antimicrobial drug (octenidine dihydrochloride,
OCT), and silica, to form highly-loaded (35% wt.) OCT-silica nanocomposite
spheres of 500 nm diameter. Drug release significantly outlasted conventional OCT
loaded mesoporous silica, closely fit Higuchi models of diffusive release, and
was visualized via electron microscopy. Extension of this concept to the broad
collection of self-assembling drugs grants biomedical community a powerful tool
for synthesizing drug-loaded inorganic nanomaterials from the bottom-up.
PMID- 29343731
TI - Impact of tissue kinetic heterogeneity on PET quantification: case study with the
L-[1-11C]leucine PET method for cerebral protein synthesis rates.
AB - Functional quantification with PET is generally based on modeling that assumes
tissue regions are kinetically homogeneous. Even in regions sufficiently small to
approach homogeneity, spillover due to resolution limitations of PET scanners may
introduce heterogeneous kinetics into measured data. Herein we consider effects
of kinetic heterogeneity at the smallest volume accessible, the single image
voxel. We used L-[1-11C]leucine PET and compared rates of cerebral protein
synthesis (rCPS) estimated voxelwise with methods that do (Spectral Analysis
Iterative Filter, SAIF) and do not (Basis Function Method, BFM) allow for kinetic
heterogeneity. In high resolution PET data with good counting statistics BFM
produced estimates of rCPS comparable to SAIF, but at lower computational cost;
thus the simpler, less costly method can be applied. With poorer counting
statistics (lower injected radiotracer doses), BFM estimates were more biased. In
data smoothed to simulate lower resolution PET, BFM produced estimates of rCPS 9
14% higher than SAIF, overestimation consistent with applying a homogeneous
tissue model to kinetically heterogeneous data. Hence with lower resolution data
it is necessary to account for kinetic heterogeneity in the analysis. Kinetic
heterogeneity may impact analyses of other tracers and scanning protocols
differently; assessments should be made on a case by case basis.
PMID- 29343732
TI - The neural correlates of the unified percept of alcohol-related craving: a fMRI
and EEG study.
AB - Alcohol addiction is accompanied by aberrant neural activity. Previously, task
based fMRI and resting-state EEG studies have revealed that craving, a critical
component of addiction, is linked to abnormal activity in cortical regions
including the dorsal anterior cingulate cortex (dACC), nucleus accumbens (NAcc),
posterior cingulate cortex (PCC) and pregenual anterior cingulate cortex (pgACC),
etc. In this study, we combine these two imaging techniques to investigate a
group of alcohol-addicted patients and provide convergent evidence for the neural
correlates of craving not only in alcohol but substance abuse in general. We
observe abnormal BOLD signal levels in the dACC, NAcc, pgACC, PCC, amygdala, and
parahippocampus (PHC) in a cue-reactivity fMRI experiment. These findings are
consistent with increased beta-band activity in the dACC and pgACC in resting
state EEG. We further observe desynchronization characterized by decreased
functional connectivity in cue-based fMRI and hypersynchronization characterized
by increased functional connectivity between these regions in the theta frequency
band. The results of our study show a consistent pattern of alcohol craving
elicited by external cues and internal desires. Given the advantage of superior
spatial and temporal resolution, we hypothesize a "central craving network" that
integrates the different aspects of alcohol addiction into a unified percept.
PMID- 29343734
TI - Cooper Pairing in A Doped 2D Antiferromagnet with Spin-Orbit Coupling.
AB - We study the two-dimensional Hubbard model with the Rashba type spin-orbit
coupling within and beyond the mean-field theory. The antiferromagnetic ground
state for the model at half-filling and the Cooper pairing induced by
antiferromagnetic spin fluctuations near half-filling are examined based on the
random-phase approximation. We show that the antiferromagnetic order is
suppressed and the magnetic susceptibility turns out to be anisotropic in the
presence of the spin-orbit coupling. Energy spectrums of transverse spin
fluctuations are obtained and the effective interactions between holes mediated
by antiferromagnetic spin fluctuations are deduced in the case of low hole
doping. It seems that the spin-orbit coupling tends to form s+p-wave Cooper
pairs, while the s+d-wave pairing is dominant when the spin-orbit coupling is
absent.
PMID- 29343733
TI - Serum vitamin D levels and risk of prevalent tuberculosis, incident tuberculosis
and tuberculin skin test conversion among prisoners.
AB - Poor vitamin D status has been associated with tuberculosis (TB); whether poor
status is cause or consequence of disease is uncertain. We conducted a case
control study and two nested case-control studies to determine whether vitamin D
levels were associated with active TB, tuberculin skin test (TST) conversion, and
risk of progression to the active TB in prisoners in Brazil. In multivariable
conditional logistic regression, subnormal vitamin D levels (OR, 3.77; 95% CI,
1.04-13.64) were more likely in prisoners with active TB. In contrast, vitamin D
was not found to be a risk factor for either TST conversion (OR, 2.49; 95% CI,
0.64-9.66) or progression to active disease (OR, 0.59; 95% CI, 0.13-2.62). Black
race (OR, 11.52; 95% CI, 2.01-63.36), less than 4 years of schooling (OR, 2.70;
95% CI, 0.90-8.16), cigarette smoking (OR, 0.23; 95% CI, 0.06-0.79) were
identified as risk factors for TST conversion. Risk of progression to active TB
was found to be associated with cigarette smoking (OR, 7.42; 95% CI, 1.23-44.70).
Our findings in the prison population show that poor vitamin D status is more
common in individuals with active TB, but is not a risk factor for acquisition of
latent TB or progression to active TB.
PMID- 29343735
TI - Increasing conversion efficiency of two-step photon up-conversion solar cell with
a voltage booster hetero-interface.
AB - Development of high-efficiency solar cells is one of the attractive challenges in
renewable energy technologies. Photon up-conversion can reduce the transmission
loss and is one of the promising concepts which improve conversion efficiency.
Here we present an analysis of the conversion efficiency, which can be increased
by up-conversion in a single-junction solar cell with a hetero-interface that
boosts the output voltage. We confirm that an increase in the quasi-Fermi gap and
substantial photocurrent generation result in a high conversion efficiency.
PMID- 29343736
TI - Establishing a mental lexicon with cochlear implants: an ERP study with young
children.
AB - In the present study we explore the implications of acquiring language when
relying mainly or exclusively on input from a cochlear implant (CI), a device
providing auditory input to otherwise deaf individuals. We focus on the time
course of semantic learning in children within the second year of implant use; a
period that equals the auditory age of normal hearing children during which
vocabulary emerges and extends dramatically. 32 young bilaterally implanted
children saw pictures paired with either matching or non-matching auditory words.
Their electroencephalographic responses were recorded after 12, 18 and 24 months
of implant use, revealing a large dichotomy: Some children failed to show
semantic processing throughout their second year of CI use, which fell in line
with their poor language outcomes. The majority of children, though, demonstrated
semantic processing in form of the so-called N400 effect already after 12 months
of implant use, even when their language experience relied exclusively on the
implant. This is slightly earlier than observed for normal hearing children of
the same auditory age, suggesting that more mature cognitive faculties at the
beginning of language acquisition lead to faster semantic learning.
PMID- 29343737
TI - Moderate decline in select synaptic markers in the prefrontal cortex (BA9) of
patients with Alzheimer's disease at various cognitive stages.
AB - Synaptic loss, plaques and neurofibrillary tangles are viewed as hallmarks of
Alzheimer's disease (AD). This study investigated synaptic markers in neocortical
Brodmann area 9 (BA9) samples from 171 subjects with and without AD at different
levels of cognitive impairment. The expression levels of vesicular glutamate
transporters (VGLUT1&2), glutamate uptake site (EAAT2), post-synaptic density
protein of 95 kD (PSD95), vesicular GABA/glycine transporter (VIAAT),
somatostatin (som), synaptophysin and choline acetyl transferase (ChAT) were
evaluated. VGLUT2 and EAAT2 were unaffected by dementia. The VGLUT1, PSD95,
VIAAT, som, ChAT and synaptophysin expression levels significantly decreased as
dementia progressed. The maximal decrease varied between 12% (synaptophysin) and
42% (som). VGLUT1 was more strongly correlated with dementia than all of the
other markers (polyserial correlation = -0.41). Principal component analysis
using these markers was unable to differentiate the CDR groups from one another.
Therefore, the status of the major synaptic markers in BA9 does not seem to be
linked to the cognitive status of AD patients. The findings of this study suggest
that the loss of synaptic markers in BA9 is a late event that is only weakly
related to AD dementia.
PMID- 29343738
TI - Critical conditions for escape of a high-speed fullerene from a BNC nanobeam
after collision.
AB - For a resonator-based nano-balance, the capability of capturing a nanoparticle is
essential for it to measure the mass of the particle. In the present study, a
clamped-clamped nanobeam from a Boron-Nitride and Carbon (BNC) nanotube acts as
the nano-balance, and a fullerene, e.g., C60, is chosen as the particle, and the
capturing capability is quantitatively estimated by the minimal escape velocity
(MEV) of the fullerene from the nanobeam after collision. When centrally
colliding with the nanobeam, the escape of fullerene depends on both incidence of
fullerene and temperature of the system. When the colliding in the Boron-Nitride
(BN) area of the beam surface, the nanoball escapes easier than that at the
carbon area. The MEV of the nanoball is lower at higher temperature. As the
nanoball sometimes slides for a few pica-seconds on the beam surface before being
bounced out, the nanoball can escape only when the beam surface can provide the
nanoball enough kinetic energy to overcome the van der Waals interaction between
them. The capturing capability of the nano-balance can, thus, be improved by
reducing the initial kinetic energy of the system.
PMID- 29343739
TI - Qualitative systematic review of barriers and facilitators to self-management of
chronic obstructive pulmonary disease: views of patients and healthcare
professionals.
AB - Self-management interventions for chronic obstructive pulmonary disease (COPD)
can improve quality of life, reduce hospital admissions, and improve symptoms.
However, many factors impede engagement for patients and practitioners.
Qualitative research, with its focus on subjective experience, can provide
invaluable insights into such factors. Therefore, a systematic review and
synthesis of qualitative evidence on COPD self-management from the perspective of
patients, carers, and practitioners was conducted. Following a systematic search
and screening, 31 studies were appraised and data extracted for analysis. This
review found that patients can adapt to COPD; however, learning to self-manage is
often a protracted process. Emotional needs are considerable; frustration,
depression, and anxiety are common. In addition, patients can face an assortment
of losses and limitations on their lifestyle and social interaction. Over time,
COPD can consume their existence, reducing motivation. Support from family can
prove vital, yet tinged with ambivalence and burden. Practitioners may not have
sufficient time, resources, or appropriate skills or confidence to provide
effective self-management support, particularly in regard to patients'
psychosocial needs. This can compound patients' capability to engage in self
management. For COPD self-management to be effective, patients' psychosocial
needs must be prioritised alongside medication and exacerbation management. In
addition, patients' personal beliefs regarding COPD and its management should be
reviewed periodically to avoid problematic behaviours and enhance positive
adaptions to the disease. Patients with COPD are not a homogenous group and no
one intervention will prove effective for all. Finally, practitioners require
greater education, training, and support to successfully assist patients.
PMID- 29343740
TI - Modifiable lifestyle behaviors, but not a genetic risk score, associate with
metabolic syndrome in evening chronotypes.
AB - Evening chronotype associates with health complications possibly via lifestyle
factors, while the contribution of genetics is unknown. The aim was to study the
relative contributions of genetics, lifestyle, and circadian-related
physiological characteristics in metabolic risk of evening chronotype. In order
to capture a biological contribution to chronotype, a genetic-risk-score (GRS),
comprised of 15 chronotype-related variants, was tested. Moreover, a wide range
of behavioral and emotional eating factors was studied within the same
population. Chronotype, lifestyle, and metabolic syndrome (MetS) outcomes were
assessed (n = 2,126), in addition to genetics (n = 1,693) and rest-activity/wrist
temperature rhythms (n = 100). Evening chronotype associated with MetS and
insulin resistance (P < 0.05), and several lifestyle factors including poorer
eating behaviors, lower physical activity and later sleep and wake times. We
observed an association between higher evening GRS and evening chronotype (P <
0.05), but not with MetS. We propose a GRS as a tool to capture the biological
component of the inter-individual differences in chronotype. Our data show that
several modifiable factors such as sedentary lifestyle, difficulties in
controlling the amount of food eaten, alcohol intake and later wake and bed times
that characterized evening-types, may underlie chronotype-MetS relationship. Our
findings provide insights into the development of strategies, particularly for
evening chronotype.
PMID- 29343742
TI - Highly effective and chemically stable surface enhanced Raman scattering
substrates with flower-like 3D Ag-Au hetero-nanostructures.
AB - We demonstrated flower-like 3D Ag-Au hetero-nanostructures on an indium tin oxide
glass (ITO glass) for surface enhanced Raman scattering (SERS) applications. The
flower-like 3D Ag nanostructures were obtained through electrodeposition with
liquid crystalline soft template which is simple, controllable and cost
effective. The flower-like 3D Ag-Au hetero-nanostructures were further fabricated
by galvanic replacement reaction of gold (III) chloride trihydrate (HAuCl4.3H2O)
solution and flower-like Ag. The flower-like Ag-Au hetero-nanostructure exhibited
stronger SERS effects and better chemical stability compared with flower-like Ag
nanostructure. The localized surface plasmon resonance (LSPR) spectra, field
emission scanning electron microscope (FESEM) photos and Ag-Au ratios were
studied which show that the surface morphology and shape of the flower-like Ag-Au
hetero-nanostructure play significant roles in enhancing SERS. The flower-like 3D
Ag-Au hetero-nanostructures fabricated by electrodeposition in liquid crystalline
template and galvanic replacement reaction are simple, cheap, controllable and
chemical stable. It is a good candidate for applications in SERS detection and
imaging.
PMID- 29343744
TI - Improved Linearity with Polarization Coulomb Field Scattering in AlGaN/GaN
Heterostructure Field-Effect Transistors.
AB - The single-tone power of the AlGaN/GaN heterostructure field-effect transistors
(HFETs) with different gate widths was measured. A distinct improvement in device
linearity was observed in the sample with a larger gate width. The analysis of
the variation of the parasitic source access resistance showed that, as the gate
bias is increased, the polarization Coulomb field scattering can offset the
increased polar optical phonon scattering and improve the device linearity. This
approach is shown to be effective in improving the device linearity of AlGaN/GaN
HFETs.
PMID- 29343743
TI - Expression and subcellular localisation of AID and APOBEC3 in adenoid and
palatine tonsils.
AB - Activation-induced cytidine deaminase (AID) and apolipoprotein B mRNA-editing
catalytic polypeptide 3 (A3) family are cytidine deaminases that play critical
roles in B-cell maturation, antiviral immunity and carcinogenesis. Adenoids and
palatine tonsils are secondary lymphoid immune organs, in which AID and A3s are
thought to have several physiological or pathological roles. However, the
expression of AID or A3s in these organs has not been investigated. Therefore, we
investigated the expression profiles of AID and A3s, using 67 samples of adenoids
and palatine tonsils from patients, with reverse transcription quantitative
polymerase chain reaction (RT-qPCR) and immunohistochemical analyses. AID and A3s
expression levels in the adenoids and the palatine tonsils of the same individual
significantly correlated with each other. Of note, AID expression level in the
adenoids negatively correlated with the age (r = -0.373, P = 0.003). The younger
group with adenoid vegetation and tonsillar hypertrophy showed more abundant AID
expression than the older group with recurrent tonsillitis and peritonsillar
abscesses (P = 0.026). Moreover, immunohistochemical analysis revealed the
distribution of AID and A3s in the epithelial cells as well as germinal centres.
The localisation of AID expression and its relation to age may contribute to
adenoid vegetation and inflammation.
PMID- 29343745
TI - Malaria infected red blood cells release small regulatory RNAs through
extracellular vesicles.
AB - The parasite Plasmodium falciparum causes the most severe form of malaria. Cell
communication between parasites is an important mechanism to control population
density and differentiation. The infected red blood cells (iRBCs) release small
extracellular vesicles (EVs) that transfer cargoes between cells. The EVs
synchronize the differentiation of the asexual parasites into gametocytes to
initiate the transmission to the mosquito. Beside their role in parasite
communication, EVs regulate vascular function. So far, the exact cargoes
responsible for cellular communication remain unknown. We isolated EVs from
cultured iRBCs to determine their small RNA content. We identified several types
of human and plasmodial regulatory RNAs. While the miRNAs and tRNA-derived
fragments were the most abundant human RNAs, we also found Y-RNAs, vault RNAs,
snoRNAs and piRNAs. Interestingly, we found about 120 plasmodial RNAs, including
mRNAs coding for exported proteins and proteins involved in drug resistance, as
well as non-coding RNAs, such as rRNAs, small nuclear (snRNAs) and tRNAs. These
data show, that iRBC-EVs carry small regulatory RNAs. A role in cellular
communication is possible since the RNAs were transferred to endothelial cells.
Furthermore, the presence of Plasmodium RNAs, in EVs suggests that they may be
used as biomarker to track and detect disease.
PMID- 29343747
TI - Computational trans-omics approach characterised methylomic and transcriptomic
involvements and identified novel therapeutic targets for chemoresistance in
gastrointestinal cancer stem cells.
AB - We investigated the relationship between methylomic [5-methylation on
deoxycytosine to form 5-methylcytosine (5mC)] and transcriptomic information in
response to chemotherapeutic 5-fluorouracil (5-FU) exposure and cisplatin (CDDP)
administration using the ornithine decarboxylase (ODC) degron-positive cancer
stem cell model of gastrointestinal tumour. The quantification of 5mC methylation
revealed various alterations in the size distribution and intensity of genomic
loci for each patient. To summarise these alterations, we transformed all large
volume data into a smooth function and treated the area as a representative value
of 5mC methylation. The present computational approach made the methylomic data
more accessible to each transcriptional unit and allowed to identify candidate
genes, including the tumour necrosis factor receptor-associated factor 4 (TRAF4),
as novel therapeutic targets with a strong response to anti-tumour agents, such
as 5-FU and CDDP, and whose significance has been confirmed in a mouse model in
vivo. The present study showed that 5mC methylation levels are inversely
correlated with gene expression in a chemotherapy-resistant stem cell model of
gastrointestinal cancer. This mathematical method can be used to simultaneously
quantify and identify chemoresistant potential targets in gastrointestinal cancer
stem cells.
PMID- 29343746
TI - The Static Magnetic Field Remotely Boosts the Efficiency of Doxorubicin through
Modulating ROS Behaviors.
AB - Exposure to magnetic field (MF) can affect cellular metabolism remotely. Cardio
toxic effects of Doxorubicin (DOXO) have limited clinical uses at high dose. MF
due to its effect on reactive oxygen species (ROS) lifetime, may provide a
suitable choice to boost the efficacy of this drug at low dose. Here, we
investigated the potential effects of homogenous static magnetic field (SMF) on
DOXO-induced toxicity and proliferation rate of cancer cells. The results
indicated that SMF similar to DOXO decreased the cell viability as well as the
proliferation rate of MCF-7 and HFF cells. Moreover, combination of 10 mT SMF and
0.1 uM DOXO decreased the viability and proliferation rate of cancer and normal
cells in a synergetic manner. In spite of high a GSH level in cancer cell, SMF
boosts the generation and lifetime of ROS at low dose of DOXO, and overcame to
GSH mediated drug resistance. The results also confirmed that SMF exposure
decreased 50% iron content of cells, which is attributed to iron homeostasis. In
conclusion, these findings suggest that SMF can decrease required dose of
chemotherapy drugs such as DOXO and thereby decrease their side effect.
PMID- 29343741
TI - Species Distribution Modelling: Contrasting presence-only models with plot
abundance data.
AB - Species distribution models (SDMs) are widely used in ecology and conservation.
Presence-only SDMs such as MaxEnt frequently use natural history collections
(NHCs) as occurrence data, given their huge numbers and accessibility. NHCs are
often spatially biased which may generate inaccuracies in SDMs. Here, we test how
the distribution of NHCs and MaxEnt predictions relates to a spatial abundance
model, based on a large plot dataset for Amazonian tree species, using inverse
distance weighting (IDW). We also propose a new pipeline to deal with
inconsistencies in NHCs and to limit the area of occupancy of the species. We
found a significant but weak positive relationship between the distribution of
NHCs and IDW for 66% of the species. The relationship between SDMs and IDW was
also significant but weakly positive for 95% of the species, and sensitivity for
both analyses was high. Furthermore, the pipeline removed half of the NHCs
records. Presence-only SDM applications should consider this limitation,
especially for large biodiversity assessments projects, when they are
automatically generated without subsequent checking. Our pipeline provides a
conservative estimate of a species' area of occupancy, within an area slightly
larger than its extent of occurrence, compatible to e.g. IUCN red list
assessments.
PMID- 29343748
TI - Sac7 and Rho1 regulate the white-to-opaque switching in Candida albicans.
AB - Candida albicans cells homozygous at the mating-type locus stochastically undergo
the white-to-opaque switching to become mating-competent. This switching is
regulated by a core circuit of transcription factors organized through
interlocking feedback loops around the master regulator Wor1. Although a range of
distinct environmental cues is known to induce the switching, the pathways
linking the external stimuli to the central control mechanism remains largely
unknown. By screening a C. albicans haploid gene-deletion library, we found that
SAC7 encoding a GTPase-activating protein of Rho1 is required for the white-to
opaque switching. We demonstrate that Sac7 physically associates with Rho1-GTP
and the constitutively active Rho1G18V mutant impairs the white-to-opaque
switching while the inactive Rho1D124A mutant promotes it. Overexpressing WOR1 in
both sac7Delta/Delta and rho1 G18V cells suppresses the switching defect,
indicating that the Sac7/Rho1 module acts upstream of Wor1. Furthermore, we
provide evidence that Sac7/Rho1 functions in a pathway independent of the
Ras/cAMP pathway which has previously been positioned upstream of Wor1. Taken
together, we have discovered new regulators and a signaling pathway that regulate
the white-to-opaque switching in the most prevalent human fungal pathogen C.
albicans.
PMID- 29343750
TI - Multi-wavelength growth of nanosecond laser-induced surface damage on fused
silica gratings.
AB - The nanosecond laser-induced damage growth phenomenon on the exit surface of
fused silica grating is investigated at 1064 nm and 355 nm separately and also
simultaneously. Experiments are first carried out on damage sites on a plane
fused silica sample showing two different morphologies, and a damage type is
selected for ensuring the repeatability of the subsequent tests. Comparing the
mono-wavelength growth results on a grating and a plane fused silica sample, the
periodic surface structure is found to be an aggravating factor for damage
growth. This is highly supported by calculations of the enhancement of the
optical electric field intensity thanks to Finite-Difference Time-Domain
simulations. Finally, the mono-wavelength results enable us to quantify a
coupling occurring in the multi-wavelength configuration, which could originate
from the heating of the plasma (more likely produced in the ultraviolet)
preferentially by the infrared pulse. This study provides interesting results
about the involvement of the surface topography in damage growth, and paves the
way towards the comprehension of this phenomenon at high-energy nanosecond laser
facilities where fused silica gratings are simultaneously irradiated at several
wavelengths.
PMID- 29343749
TI - Testosterone boosts physical activity in male mice via dopaminergic pathways.
AB - Low testosterone (T) in men, especially its free fraction, has been associated
with loss of energy. In accordance, orchidectomy (ORX) in rodents results in
decreased physical activity. Still, the mechanisms through which T stimulates
activity remain mostly obscure. Here, we studied voluntary wheel running behavior
in three different mouse models of androgen deficiency: ORX, androgen receptor
(AR) knock-out (ARKO) and sex hormone binding globulin (SHBG)-transgenic mice, a
novel mouse model of "low free T". Our results clearly show a fast and dramatic
action of T stimulating wheel running, which is not explained by its action on
muscle, as evidenced by neuromuscular studies and in a muscle-specific
conditional ARKO mouse model. The action of T occurs via its free fraction, as
shown by the results in SHBG-transgenic mice, and it implies both androgenic and
estrogenic pathways. Both gene expression and functional studies indicate that T
modulates the in vivo sensitivity to dopamine (DA) agonists. Furthermore, the
restoration of wheel running by T is inhibited by treatment with DA antagonists.
These findings reveal that the free fraction of T, both via AR and indirectly
through aromatization into estrogens, stimulates physical activity behavior in
male mice by acting on central DA pathways.
PMID- 29343751
TI - Altered power spectral density in the resting-state sensorimotor network in
patients with myotonic dystrophy type 1.
AB - Myotonic dystrophy type 1 (DM1) is a multisystemic disease that involves the
brain with several neurological symptoms. Although there were few imaging studies
on DM1, no studies have investigated functional alterations in the sensorimotor
network at rest in patients with DM1. In the current study, a power spectral
density (PSD) analysis of resting-state fMRI data was performed to assess
possible alteration in spontaneous neural activity of the sensorimotor network in
patients with DM1. Compared to healthy controls, patients with DM1 showed higher
PSD responses in the orbitofrontal cortex, parahippocampus and basal ganglia
(corrected P < 0.05). Patients with DM1 showed higher PSD responses in white
matter structures associated with motor function (corrected P < 0.05).
Furthermore, correlation analysis indicated that the brain regions showing PSD
differences were correlated with measures of motor performance (P < 0.05). In
gray matter, our findings suggest that motor disability in DM1 is not an isolated
deterioration of the motor power but a multimodal dysfunction that also involves
the visual system. In addition, the widespread PSD alteration in white matter
structures suggest that motor deficits in DM1 involve motor movement structures
as well as structures important for its coordination and regulation.
PMID- 29343752
TI - Counting Caenorhabditis elegans: Protocol Optimization and Applications for
Population Growth and Toxicity Studies in Liquid Medium.
AB - The nematode Caenorhabditis elegans is used extensively in molecular,
toxicological and genetics research. However, standardized methods for counting
nematodes in liquid culture do not exist despite the wide use of nematodes and
need for accurate measurements. Herein, we provide a simple and affordable
counting protocol developed to maximize count accuracy and minimize variability
in liquid nematode culture. Sources of variability in the counting process were
identified and tested in 14 separate experiments. Three variables resulted in
significant effects on nematode count: shaking of the culture, priming of pipette
tips, and sampling location within a microcentrifuge tube. Between-operator
variability did not have a statistically significant effect on counts, even among
differently-skilled operators. The protocol was used to assess population growth
rates of nematodes in two different but common liquid growth media: axenic
modified Caenorhabditis elegans Habitation and Reproduction medium (mCeHR) and S
basal complete. In mCeHR, nematode populations doubled daily for 10 d. S-basal
complete populations initially doubled every 12 h, but slowed within 7 d. We also
detected a statistically significant difference between embryo-to-hatchling
incubation period of 5 d in mCeHR compared to 4 d in S-basal complete. The
developed counting method for Caenorhabditis elegans reduces variability and
allows for rigorous and reliable experimentation.
PMID- 29343753
TI - Procalcitonin as a Biomarker for Malignant Cerebral Edema in Massive Cerebral
Infarction.
AB - The objective of this study is to explore whether procalcitonin (PCT) can serve
as an early biomarker of malignant cerebral edema in patients with massive
cerebral infarction (MCI). Ninety-three patients with acute MCI were divided into
death or survival groups based on whether they died or survived within 1 week of
cerebral herniation. Differences in laboratory parameters between these two
groups were analyzed by univariate analysis, followed by multivariate logistic
regression analyses if the influencing factors were significantly different.
Compared with the survival group, the patients in the death group had a larger
cerebral infarct area, higher body temperature, neutrophil counts, PCT level, and
neuron-specific enolase (NSE) level within 48 h of onset. Multivariate logistic
regression analyses revealed an odds ratio (OR) of 1.830 or 1.235 for PCT and
neutrophil counts respectively, suggesting that PCT and neutrophil counts are two
independent risk factors for death in MCI. The area under receiver operating
characteristic (ROC) curve was 0.754 for PCT, larger than that for neutrophil
counts. Thus, both serum PCT levels and neutrophil counts can be used as
biomarkers to predict malignant cerebral edema at the early stages after MCI, but
PCT levels are superior predictors of malignant cerebral edema.
PMID- 29343754
TI - Development and validation of a brief diabetic foot ulceration risk checklist
among diabetic patients: a multicenter longitudinal study in China.
AB - The study aims to develop and assess and validate a brief diabetic foot
ulceration risk checklist among diabetic patients through a longitudinal study.
Patients who had diabetes mellitus and had no foot ulceration and severe
systematic disorders were recruited from eleven tertiary hospitals in nine
provinces or municipalities of China. Internal consistency reliability, construct
validity, concurrent validity, item property, and measurement invariance of the
tool were assessed. The predictive capability of the tool was validated by the
follow-up data using the receiver operating characteristic curve. At baseline,
477 valid cases were collected. Twelve items were remained after initial
selection. Cronbach's alpha was 0.56. Confirmatory factor analysis showed that
the model had acceptable goodness-of-fit yet local dependency between two items.
Item response theory showed that most items had acceptable discrimination and
difficulty parameters. Differential item functioning showed that tool had
measurement invariance. 278 were followed up one year after the baseline. Follow
up showed that one-year incidence of ulceration among the patients was 3.6%, and
the area under the receiver operating characteristic curve was 0.77 (95%
confidence interval: 0.61-0.93). The cut-off point of the tool was 4, when
sensitivity and specificity were 0.62 and 0.75 respectively. The checklist has
good psychometric properties according to mixed evidences from classical and
modern test theory, and has good predictive capability.
PMID- 29343755
TI - Significantly High Modulation Efficiency of Compact Graphene Modulator Based on
Silicon Waveguide.
AB - We theoretically and experimentally demonstrate a significantly large modulation
efficiency of a compact graphene modulator based on a silicon waveguide using the
electro refractive effect of graphene. The modulation modes of electro-absorption
and electro-refractive can be switched with different applied voltages. A high
extinction ratio of 25 dB is achieved in the electro-absorption modulation mode
with a driving voltage range of 0 V to 1 V. For electro-refractive modulation,
the driving voltage ranges from 1 V to 3 V with a 185-pm spectrum shift. The
modulation efficiency of 1.29 V . mm with a 40-MUm interaction length is two
orders of magnitude higher than that of the first reported graphene phase
modulator. The realisation of phase and intensity modulation with graphene based
on a silicon waveguide heralds its potential application in optical communication
and optical interconnection systems.
PMID- 29343756
TI - Radiological and clinical differences among three assisted technologies in
pedicle screw fixation of adult degenerative scoliosis.
AB - The purpose of this study was to compare the clinical and radiological
differences among three advanced guided technologies in adult degenerative
scoliosis. A total of 1012 pedicle screws were inserted in 83 patients using a
spine robot (group A), 886 screws were implanted in 75 patients using a drill
guide template (group B), and 1276 screws were inserted in 109 patients using CT
based navigation (group C). Screw positions were evaluated using postoperative CT
scans according to the Gertzbein and Robbins classification. Other relevant data
were also collected. Perfect pedicle screw insertion (Grade A) accuracy in groups
A, B, and C was 91.3%, 81.3%, and 84.1%, respectively. Clinically acceptable
accuracy of screw implantation (Grades A + B) respectively was 96.0%, 90.6%, and
93.0%. Statistical analysis showed the perfect and clinically acceptable accuracy
in group A was significant different compared with groups B and C. Group A
exhibited the lowest intra-op radiation dose and group B showed the shortest
surgical time compared with the other two groups. Robotic-assisted technology
demonstrated significantly higher accuracy than the drill guide template or CT
based navigation systems for difficult screw implantations in adult degenerative
scoliosis and reduced the intra-op radiation dose, although it failed to reduce
surgery time.
PMID- 29343757
TI - The early conversion of deep-sea wood falls into chemosynthetic hotspots revealed
by in situ monitoring.
AB - Wood debris on the ocean floor harbor flourishing communities, which include
invertebrate taxa thriving in sulfide-rich habitats belonging to hydrothermal
vent and methane seep deep-sea lineages. The formation of sulfidic niches from
digested wood material produced by woodborers has been known for a long time, but
the temporal dynamics and sulfide ranges encountered on wood falls remains
unknown. Here, we show that wood falls are converted into sulfidic hotpots,
before the colonization by xylophagaid bivalves. Less than a month after
immersion at a depth of 520 m in oxygenated seawater the sulfide concentration
increased to millimolar levels inside immersed logs. From in situ experiments
combining high-frequency chemical and video monitoring, we document the rapid
development of a microbial sulfur biofilm at the surface of wood. These findings
highlight the fact that sulfide is initially produced from the labile components
of wood and supports chemosynthesis as an early pathway of energy transfer to
deep-sea wood colonists, as suggested by recent aquarium studies. The study
furthermore reveals that woodborers promote sulfide-oxidation at the periphery of
their burrows, thus, not only facilitating the development of sulfidic zones in
the surrounding of degraded wood falls, but also governing sulfur-cycling within
the wood matrix.
PMID- 29343758
TI - Electronic Properties of Synthetic Shrimp Pathogens-derived DNA Schottky Diodes.
AB - The exciting discovery of the semiconducting-like properties of deoxyribonucleic
acid (DNA) and its potential applications in molecular genetics and diagnostics
in recent times has resulted in a paradigm shift in biophysics research. Recent
studies in our laboratory provide a platform towards detecting charge transfer
mechanism and understanding the electronic properties of DNA based on the
sequence-specific electronic response, which can be applied as an alternative to
identify or detect DNA. In this study, we demonstrate a novel method for
identification of DNA from different shrimp viruses and bacteria using electronic
properties of DNA obtained from both negative and positive bias regions in
current-voltage (I-V) profiles. Characteristic electronic properties were
calculated and used for quantification and further understanding in the
identification process. Aquaculture in shrimp industry is a fast-growing food
sector throughout the world. However, shrimp culture in many Asian countries
faced a huge economic loss due to disease outbreaks. Scientists have been using
specific established methods for detecting shrimp infection, but those methods do
have their significant drawbacks due to many inherent factors. As such, we
believe that this simple, rapid, sensitive and cost-effective tool can be used
for detection and identification of DNA from different shrimp viruses and
bacteria.
PMID- 29343759
TI - Incorporation of iloprost in phospholipase-resistant phospholipid scaffold
enhances its barrier protective effects on pulmonary endothelium.
AB - Correction of barrier dysfunction and inflammation in acute lung injury (ALI)
represents an important problem. Previous studies demonstrate barrier-protective
and anti-inflammatory effects of bioactive lipid prostacyclin and its stable
analog iloprost (ILO). We generated a phospholipase resistant synthetic
phospholipid with iloprost attached at the sn-2 position (ILO-PC) and
investigated its biological effects. In comparison to free ILO, ILO-PC caused
sustained endothelial cell (EC) barrier enhancement, linked to more prolonged
activation of Rap1 and Rac1 GTPases and their cytoskeletal and cell junction
effectors: cortactin, PAK1, p120-catenin and VE-cadherin. ILO and ILO-PC equally
efficiently suppressed acute, Rho GTPase-dependent EC hyper-permeability caused
by thrombin. However, ILO-PC exhibited more sustained barrier-protective and anti
inflammatory effects in the model of chronic EC dysfunction caused by bacterial
wall lipopolysacharide (LPS). ILO-PC was also more potent inhibitor of NFkappaB
signaling and lung vascular leak in the murine model of LPS-induced ALI.
Treatment with ILO-PC showed more efficient ALI recovery over 3 days after LPS
challenge than free ILO. In conclusion, this study describes a novel synthetic
phospholipid with barrier-enhancing and anti-inflammatory properties superior to
existing prostacyclin analogs, which may be used as a prototype for future
development of more efficient treatment for ALI and other vascular leak
syndromes.
PMID- 29343760
TI - Large-scale semi-arid afforestation can enhance precipitation and carbon
sequestration potential.
AB - Afforestation is an important approach to mitigate global warming. Its complex
interactions with the climate system, however, makes it controversial.
Afforestation is expected to be effective in the tropics where biogeochemical and
biogeophysical effects act in concert; however, its potential in the large semi
arid regions remains insufficiently explored. Here, we use a Global Climate Model
to provide a process-based demonstration that implementing measured
characteristics of a successful semi-arid afforestation system (2000 ha, ~300 mm
mean annual precipitation) over large areas (~200 million ha) of similar
precipitation levels in the Sahel and North Australia leads to the weakening and
shifting of regional low-level jets, enhancing moisture penetration and
precipitation (+0.8 +/- 0.1 mm d-1 over the Sahel and +0.4 +/- 0.1 mm d-1 over
North Australia), influencing areas larger than the original afforestation. These
effects are associated with increasing root depth and surface roughness and with
decreasing albedo. This results in enhanced evapotranspiration, surface cooling
and the modification of the latitudinal temperature gradient. It is estimated
that the carbon sequestration potential of such large-scale semi-arid
afforestation can be on the order of ~10% of the global carbon sink of the land
biosphere and would overwhelm any biogeophysical warming effects within ~6 years.
PMID- 29343761
TI - A high throughput approach for the generation of orthogonally interacting protein
pairs.
AB - In contrast to the nearly error-free self-assembly of protein architectures in
nature, artificial assembly of protein complexes with pre-defined structure and
function in vitro is still challenging. To mimic nature's strategy to construct
pre-defined three-dimensional protein architectures, highly specific protein
protein interacting pairs are needed. Here we report an effort to create an
orthogonally interacting protein pair from its parental pair using a bacteria
based in vivo directed evolution strategy. This high throughput approach features
a combination of a negative and a positive selection. The newly developed
negative selection from this work was used to remove any protein mutants that
retain effective interaction with their parents. The positive selection was used
to identify mutant pairs that can engage in effective mutual interaction. By
using the cohesin-dockerin protein pair that is responsible for the self-assembly
of cellulosome as a model system, we demonstrated that a protein pair that is
orthogonal to its parent pair could be readily generated using our strategy. This
approach could open new avenues to a wide range of protein-based assembly, such
as biocatalysis or nanomaterials, with pre-determined architecture and
potentially novel functions and properties.
PMID- 29343762
TI - Mercury sodium exospheric emission as a proxy for solar perturbations transit.
AB - The first evidence at Mercury of direct relation between ICME transit and Na
exosphere dynamics is presented, suggesting that Na emission, observed from
ground, could be a proxy of planetary space weather at Mercury. The link existing
between the dayside exosphere Na patterns and the solar wind-magnetosphere
surface interactions is investigated. This goal is pursued by analyzing the Na
intensity hourly images, as observed by the ground-based THEMIS solar telescope
during 10 selected periods between 2012 and 2013 (with seeing, sigma < = 2"),
when also MESSENGER data were available. Frequently, two-peak patterns of
variable intensity are observed, located at high latitudes in both hemispheres.
Occasionally, Na signal is instead diffused above the sub-solar region. We
compare these different patterns with the in-situ time profiles of proton fluxes
and magnetic field data from MESSENGER. Among these 10 cases, only in one
occasion the Na signal is diffused above the subsolar region, when the MESSENGER
data detect the transit of two ICMEs. The selected cases suggest that the Na
emission patterns are well related to the solar wind conditions at Mercury.
Hence, the exospheric Na emission patterns, observed from ground, could be
considered as a 'natural monitor' of solar disturbances when transiting near
Mercury.
PMID- 29343763
TI - Association of S100B polymorphisms and serum S100B with risk of ischemic stroke
in a Chinese population.
AB - The levels of serum S100B were elevated in patients with ischemic stroke (IS),
which may be a novel biomarker for diagnosing IS. The aim of this study was to
investigate the association of S100B polymorphisms and serum S100B with IS risk.
We genotyped the S100B polymorphisms rs9722, rs9984765, rs2839356, rs1051169 and
rs2186358 in 396 IS patients and 398 controls using polymerase chain reaction
single base extension (SBE-PCR). Serum S100B levels were measured by enzyme
linked immunosorbent assay (ELISA). Rs9722 was associated with an increased risk
of IS (AA vs. GG: adjusted OR = 2.172, 95% CI, 1.175-4.014, P = 0.013; dominant:
adjusted OR = 1.507, 95% CI, 1.071-2.123, P = 0.019; recessive: adjusted OR =
1.846, 95% CI, 1.025-3.323, P = 0.041; additive: adjusted OR=1.371, 95% CI, 1.109
1.694, P = 0.003). The A-C-C-C-A haplotype was associated with an increased risk
of IS (OR = 1.325, 95% CI, 1.035-1.696, P = 0.025). In addition, individuals
carrying the rs9722 GA/AA genotypes had a higher serum S100B compared with the
rs9722 GG genotype in IS patients (P = 0.018). Our results suggest that the S100B
gene rs9722 polymorphism may contribute to the susceptibility of IS, probably by
promoting the expression of serum S100B.
PMID- 29343765
TI - Regulation of Signaling Pathways Involved in the Anti-proliferative and Apoptosis
inducing Effects of M22 against Non-small Cell Lung Adenocarcinoma A549 Cells.
AB - The compound 29-(4-methylpiperazine)-luepol (M22), a novel derivative of lupeol
has shown anti-proliferative effects against the human non-small cell lung cancer
A549 cell line. M22 showed significant anti-proliferative activity at 6.80 MUM
and increased accumulation of G1 cells and effectively suppressed expression of
the G1 arrest-related genes cyclins D1 and E1, CDK2 and CDC25A. This was further
confirmed by Western blotting demonstrating decreased cyclin D1 and CDC25A
protein levels. Furthermore, M22 caused induction of apoptosis that downregulated
the anti-apoptotic BCL-2 gene and increased expression of BAX, CASP3 and CASP9 as
well as the APAF1 gene. The effect of caspase-induced apoptosis was confirmed by
an increase in reactive oxygen species (ROS), loss of mitochondrial membrane
potential (MMP). Taken together, our findings indicated that M22 possessed potent
anti-proliferative and apoptotic activities.
PMID- 29343766
TI - Sudden sensory neural hearing loss is not predictive of myocardial infarction: A
longitudinal follow-up study using a national sample cohort.
AB - The aim of this study was to evaluate the risk of myocardial infarction (MI) in
SSNHL subjects with differently matched control groups. The Korean Health
Insurance Review and Assessment Service - National Sample Cohort recruited
subjects from 2002 to 2013. We used two study designs. In study I, we matched
4,467 SSNHL participants with a control group (17,868 subjects with no history of
SSNHL) based on demographic factors (age, sex, income, and region of residence)
and medical history (diabetes, dyslipidemia, and hypertension). In study II, we
matched 4,467 SSNHL participants with a control group based on only demographic
factors. The crude (simple) and adjusted hazard ratios (HRs) of SSNHL with MI
were analyzed using the Cox-proportional hazard model. In study I, SSNHL was not
associated with increased risk of MI. However, in study II, SSNHL was associated
with increased risk of MI (adjusted HR = 1.39 95% CI = 1.00-1.93, P = 0.048). The
SSNHL group did not exhibit increased risk of MI when compared to the control
group matched by both demographic factors and medical history. However, compared
to the control group not matched by medical history, the relative risk of MI was
increased in the SSNHL group.
PMID- 29343767
TI - Blockade of TRPV1 Inhibits Methamphetamine-induced Rewarding Effects.
AB - Methamphetamine (MAP) is the most widely used psychostimulant in the world, but
the exact mechanisms underlying MAP addiction are not yet fully understood.
Recent studies have identified the distribution of TRPV1 in several brain regions
that are related to drug addiction, including nucleus accumbens (NAc) and dorsal
striatum (DSt). In the present study, we performed conditioned place preference
(CPP) and self-administration tests to examine the effects of capsazepine (CPZ)
and SB366791 (SB) on MAP reward. We found that both CPZ and SB significantly
inhibited MAP-induced CPP and self-administration; in contrast, TRPV1 knock-out
(KO) mice did not develop MAP-induced CPP. Real-time RT-PCR, Western blot and
quantitative autoradiographic tests showed up-regulation of TRPV1 mRNA and
protein expression in the NAc and/or DSt regions of mice exhibiting MAP-induced
CPP. In addition, an in vivo microdialysis experiment showed that CPZ
dramatically reduced dopamine (DA) levels in the NAc region of MAP-treated mice.
Furthermore, attenuated dopamine transporter (DAT) binding levels in the NAc and
DSt regions of MAP-induced CPP mice were reversed by CPZ. Together, these data
suggest that TRPV1 plays an important role in MAP reward via the modulation of DA
release and DAT density, thereby providing a novel therapeutic target for MAP
addiction.
PMID- 29343768
TI - Broadband Asymmetric Light Transmission at Metal/Dielectric Composite Grating.
AB - Optical diode-like effect has sparked growing interest in recent years due to its
potential applications in integrated photonic systems. In this paper, we propose
and numerically demonstrate a new type of easy-processing metal/dielectric
cylinder composite grating on semi-sphere substrate, which can achieve high
contrast asymmetric transmission of unpolarized light for the sum of all
diffraction modes in the entire visible region, and effectively guide the
diffraction light transmitting out the substrate. The asymmetric light
transmission (ALT) ratio is larger than 2 dB in the waveband from 380 nm to 780
nm and the maximum ALT ratio can reach to 13 dB at specified wavelengths. The
thorough theoretical research reveals that the proposed metal/dielectric pillar
composite grating structure, together with the substrate, can effectively excite
localized surface plasmonic resonance (LSPR) effect and waveguide mode (WGM), and
enlarge the diffraction difference between forward and backward transmission
spaces, including both number of diffraction orders and diffraction efficiency,
thus resulting in high-contrast broadband ALT phenomenon. In particular, lowering
the symmetry of the grating can achieve polarization-dependent ALT. Such a type
of easy-processing ALT device with high performance for both polarized and
unpolarized light can be regarded as suitable candidates in practical
applications.
PMID- 29343764
TI - Genome-wide association study in 79,366 European-ancestry individuals informs the
genetic architecture of 25-hydroxyvitamin D levels.
AB - Vitamin D is a steroid hormone precursor that is associated with a range of human
traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations
have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1,
CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS
discovery sample size from 16,125 to 79,366 (all European descent). This larger
GWAS yields two additional loci harboring genome-wide significant variants (P =
4.7*10-9 at rs8018720 in SEC23A, and P = 1.9*10-14 at rs10745742 in AMDHD1). The
overall estimate of heritability of 25-hydroxyvitamin D serum concentrations
attributable to GWAS common SNPs is 7.5%, with statistically significant loci
explaining 38% of this total. Further investigation identifies signal enrichment
in immune and hematopoietic tissues, and clustering with autoimmune diseases in
cell-type-specific analysis. Larger studies are required to identify additional
common SNPs, and to explore the role of rare or structural variants and gene-gene
interactions in the heritability of circulating 25-hydroxyvitamin D levels.
PMID- 29343769
TI - CKAMP44 modulates integration of visual inputs in the lateral geniculate nucleus.
AB - Relay neurons in the dorsal lateral geniculate nucleus (dLGN) receive excitatory
inputs from retinal ganglion cells (RGCs). Retinogeniculate synapses are
characterized by a prominent short-term depression of AMPA receptor (AMPAR)
mediated currents, but the underlying mechanisms and its function for visual
integration are not known. Here we identify CKAMP44 as a crucial auxiliary
subunit of AMPARs in dLGN relay neurons, where it increases AMPAR-mediated
current amplitudes and modulates gating of AMPARs. Importantly, CKAMP44 is
responsible for the distinctive short-term depression in retinogeniculate
synapses by reducing the rate of recovery from desensitization of AMPARs. Genetic
deletion of CKAMP44 strongly reduces synaptic short-term depression, which leads
to increased spike probability of relay neurons when activated with high
frequency inputs from retinogeniculate synapses. Finally, in vivo recordings
reveal augmented ON- and OFF-responses of dLGN neurons in CKAMP44 knockout
(CKAMP44-/-) mice, demonstrating the importance of CKAMP44 for modulating
synaptic short-term depression and visual input integration.
PMID- 29343770
TI - Reconstructing the gradient source position from steady-state fluxes to small
receptors.
AB - Recovering the position of a source from the fluxes of diffusing particles
through small receptors allows a biological cell to determine its relative
position, spatial localization and guide it to a final target. However, how a
source can be recovered from point fluxes remains unclear. Using the Narrow
Escape approach for an open domain, we compute the diffusion fluxes of Brownian
particles generated by a steady-state gradient from a single source through small
holes distributed on a surface in two dimensions. We find that the location of a
source can be recovered when there are at least 3 receptors and the source is
positioned no further than 10 cell radii away, but this condition is not
necessary in a narrow strip. The present approach provides a computational basis
for the first step of direction sensing of a gradient at a single cell level.
PMID- 29343772
TI - Shape-matching soft mechanical metamaterials.
AB - Architectured materials with rationally designed geometries could be used to
create mechanical metamaterials with unprecedented or rare properties and
functionalities. Here, we introduce "shape-matching" metamaterials where the
geometry of cellular structures comprising auxetic and conventional unit cells is
designed so as to achieve a pre-defined shape upon deformation. We used
computational models to forward-map the space of planar shapes to the space of
geometrical designs. The validity of the underlying computational models was
first demonstrated by comparing their predictions with experimental observations
on specimens fabricated with indirect additive manufacturing. The forward-maps
were then used to devise the geometry of cellular structures that approximate the
arbitrary shapes described by random Fourier's series. Finally, we show that the
presented metamaterials could match the contours of three real objects including
a scapula model, a pumpkin, and a Delft Blue pottery piece. Shape-matching
materials have potential applications in soft robotics and wearable (medical)
devices.
PMID- 29343771
TI - Magnetoencephalographic Correlates of Perceptual State During Auditory
Bistability.
AB - Bistability occurs when two alternative percepts can be derived from the same
physical stimulus. To identify the neural correlates of specific subjective
experiences we used a bistable auditory stimulus and determined whether the two
perceptual states could be distinguished electrophysiologically. Fourteen
participants underwent magnetoencephalography while reporting their perceptual
experience while listening to a continuous bistable stream of auditory tones.
Participants reported bistability with a similar overall proportion of the two
alternative percepts (52% vs 48%). At the individual level, sensor space
electrophysiological discrimination between the percepts was possible in 9/14
participants with canonical variate analysis (CVA) or linear support vector
machine (SVM) analysis over space and time dimensions. Classification was
possible in 14/14 subjects with non-linear SVM. Similar effects were noted in an
unconstrained source space CVA analysis (classifying 10/14 participants), linear
SVM (classifying 9/14 subjects) and non-linear SVM (classifiying 13/14
participants). Source space analysis restricted to a priori ROIs showed
discrimination was possible in the right and left auditory cortex with each
classification approach but in the right intraparietal sulcus this was only
apparent with non-linear SVM and only in a minority of particpants.
Magnetoencephalography can be used to objectively classify auditory experiences
from individual subjects.
PMID- 29343773
TI - Mitochondrial Mutations in Cholestatic Liver Disease with Biliary Atresia.
AB - Biliary atresia (BA) results in severe bile blockage and is caused by the absence
of extrahepatic ducts. Even after successful hepatic portoenterostomy, a
considerable number of patients are likely to show progressive deterioration in
liver function. Recent studies show that mutations in protein-coding
mitochondrial DNA (mtDNA) genes and/or mitochondrial genes in nuclear DNA (nDNA)
are associated with hepatocellular dysfunction. This observation led us to
investigate whether hepatic dysfunctions in BA is genetically associated with
mtDNA mutations. We sequenced the mtDNA protein-coding genes in 14 liver
specimens from 14 patients with BA and 5 liver specimens from 5 patients with
choledochal cyst using next-generation sequencing. We found 34 common non
synonymous variations in mtDNA protein-coding genes in all patients examined. A
systematic 3D structural analysis revealed the presence of several single
nucleotide polymorphism-like mutations in critical regions of complexes I to V,
that are involved in subunit assembly, proton-pumping activity, and/or
supercomplex formation. The parameters of chronic hepatic injury and liver
dysfunction in BA patients were also significantly correlated with the extent of
hepatic failure, suggesting that the mtDNA mutations may aggravate hepatopathy.
Therefore, mitochondrial mutations may underlie the pathological mechanisms
associated with BA.
PMID- 29343774
TI - An improved method of crafting a multi-electrode spiral cuff for the selective.
AB - This article reviews an improved methodology and technology for crafting a multi
electrode spiral cuff for the selective activation of nerve fibres in particular
superficial regions of a peripheral nerve. The analysis, structural and
mechanical properties of the spot welds used for the interconnections between the
stimulating electrodes and stainless-steel lead wires are presented. The cuff
consisted of 33 platinum electrodes embedded within a self-curling 17-mm-long
silicone spiral sheet with a nominal internal diameter of 2.5 mm. The weld was
analyzed using scanning electron microscopy and nanohardness tests, while the
interconnection was investigated using destructive load tests. The functionality
of the cuff was tested in an isolated porcine vagus nerve. The results of the
scanning electron microscopy show good alloying and none of the typical welding
defects that occur between the wire and the platinum foil. The results of the
destructive load tests show that the breaking loads were between 3.22 and 5 N.
The results of the nanohardness testing show that the hardness of the weld was
different for the particular sites on the weld sample. Finally, the results of
the functional testing show that for different stimulation intensities both the
compound action potential deflection and the shape are modulated.
PMID- 29343775
TI - Impact of Concurrent Genomic Alterations Detected by Comprehensive Genomic
Sequencing on Clinical Outcomes in East-Asian Patients with EGFR-Mutated Lung
Adenocarcinoma.
AB - Next-generation sequencing (NGS) has enabled comprehensive detection of genomic
alterations in lung cancer. Ethnic differences may play a critical role in the
efficacy of targeted therapies. The aim of this study was to identify and compare
genomic alterations of lung adenocarcinoma between Japanese patients and the
Cancer Genome Atlas (TCGA), which majority of patients are from the US. We also
aimed to examine prognostic impact of additional genomic alterations in patients
harboring EGFR mutations. Genomic alterations were determined in Japanese
patients with lung adenocarcinoma (N = 100) using NGS-based sequencing of 415
known cancer genes, and correlated with clinical outcome. EGFR active mutations,
i.e., those involving exon 19 deletion or an L858R point mutation, were seen in
43% of patients. Some differences in driver gene mutation prevalence were
observed between the Japanese cohort described in the present study and the TCGA.
Japanese cohort had significantly more genomic alterations in cell cycle pathway,
i.e., CDKN2B and RB1 than TCGA. Concurrent mutations, in genes such as CDKN2B or
RB1, were associated with worse clinical outcome in patients with EGFR active
mutations. Our data support the utility of comprehensive sequencing to detect
concurrent genomic variations that may affect clinical outcomes in this disease.
PMID- 29343776
TI - Critical Shear Stress is Associated with Diabetic Kidney Disease in Patients with
Type 2 Diabetes.
AB - Critical shear stress (CSS, mPa) is an index of red blood cell (RBC)
aggregability, defined as the minimal shear stress required to disperse RBC
aggregates. This study aimed to investigate the association between CSS and the
risk of diabetic kidney disease (DKD). A total of 421 (mean age, 58.1 +/- 11.5
years; male, 250) individuals with T2DM were enrolled and divided into three
groups according to CSS level. CSS was measured using a transient microfluidic
technique. DKD was defined as a glomerular filtration rate (GFR) <60 ml/min/1.73
m2 or a urine albumin-to-creatinine ratio (uACR) >=30 mg/g. CSS was significantly
higher in patients with DKD than in those without (317.43 +/- 125.11 vs 385.22 +/
182.89, p < 0.001). Compared to the lowest CSS tertile, the highest CSS tertile
was independently associated with the risk of DKD after adjusting for age, sex,
duration of diabetes, presence of hypertension and haemoglobin. The cut-off value
of CSS for DKD was approximately 310 mPa. These results suggest that
haemorheologic changes may contribute to DKD, and further prospective studies are
warranted to determine the role of CSS as a DKD screening tool.
PMID- 29343777
TI - The hidden cost of using low-resolution concentration data in the estimation of
NH3 dry deposition fluxes.
AB - Long-term monitoring stations for atmospheric pollutants are often equipped with
low-resolution concentration samplers. In this study, we analyse the errors
associated with using monthly average ammonia concentrations as input variables
for bidirectional biosphere-atmosphere exchange models, which are commonly used
to estimate dry deposition fluxes. Previous studies often failed to account for a
potential correlation between ammonia exchange velocities and ambient
concentrations. We formally derive the exact magnitude of these errors from
statistical considerations and propose a correction scheme based on parallel
measurements using high-frequency analysers. In case studies using both modelled
and measured ammonia concentrations and micrometeorological drivers from sites
with varying pollution levels, we were able to substantially reduce bias in the
predicted ammonia fluxes. Neglecting to account for these errors can, in some
cases, lead to significantly biased deposition estimates compared to using high
frequency instrumentation or corrected averaging strategies. Our study presents a
first step towards a unified correction scheme for data from nation-wide air
pollutant monitoring networks to be used in chemical transport and air quality
models.
PMID- 29343778
TI - Fumarate-based metal-organic frameworks as a new platform for highly selective
removal of fluoride from brick tea.
AB - Adsorption and removal of fluoride from brick tea is very important but
challenging. In this work, two fumarate-based metal-organic frameworks (MOFs)
were synthesized for the selective removal of fluoride from brick tea infusion.
MOFs were examined for adsorption time, effect of dose, and uptake capacity at
different initial concentrations and temperatures. Remarkably, over 80% fluoride
removal was achieved by MOF-801 within 5 min at room temperature, while no
significant adsorption occurred for the catechins and caffeine in the brick tea
infusion. Further, with the use of the Langmuir equation, the maximum fluoride
uptake capacity for the nontoxic calcium fumarate (CaFu) MOF was calculated to be
as high as 166.11 mg g-1 at 373 K. As observed from FTIR, EDX and XPS results,
hydroxyl group in MOFs were substituted by fluoride. This work demonstrates that
the novel fumarate-based MOFs are promising materials for the selective removal
of fluoride from brick tea infusion.
PMID- 29343780
TI - Waste Windshield-Derived Silicon/Carbon Nanocomposites as High-Performance
Lithium-Ion Battery Anodes.
AB - Silicon has emerged as the most promising high-capacity material for lithium-ion
batteries. Waste glass can be a potential low cost and environmentally benign
silica resource enabling production of nanosized silicon at the industry level.
Windshields are generally made of laminated glass comprising two separate glass
bonded together with a layer of polyvinyl butyral sandwiched between them.
Herein, silicon/carbon nanocomposites are fabricated from windshields for the
first time via magnesiothermic reduction and facile carbonization process using
both waste glass and polyvinyl butyral as silica and carbon sources,
respectively. High purity reduced silicon has unique 3-dimensional nanostructure
with large surface area. Furthermore, the incorporation of carbon in silicon
enable to retain the composite anodes highly conductive and mechanically robust,
thus providing enhanced cycle stability.
PMID- 29343779
TI - Characterization of signaling pathways regulating the expression of pro
inflammatory long form thymic stromal lymphopoietin upon human metapneumovirus
infection.
AB - Thymic stromal lymphopoietin (TSLP) is associated with several allergic diseases
including asthma. Two isoforms of TSLP exist in humans, a long form (lfTSLP) and
a short form (sfTSLP), displaying distinct immunological functions. Recently,
TSLP was found to be upregulated in human airway cells upon human metapneumovirus
(hMPV) infection, yet it remains unclear if the two isoforms are regulated
differently during hMPV infection. Importantly, the molecular mechanisms
underlying hMPV-mediated TSLP induction remain undescribed. In this study, we
characterized the expression and regulation of TSLP in hMPV-infected human airway
cells. We demonstrated that hMPV strongly induced the expression of pro
inflammatory lfTSLP in human airway epithelial cells and lung fibroblasts.
Further, knockdown of pattern recognition receptors retinoic acid-inducible gene
I (RIG-I) or Toll-like receptor 3 (TLR3), as well as downstream signal
transducers, abrogated hMPV-mediated lfTSLP induction. Importantly, silencing of
TANK-binding kinase 1 (TBK1) also impaired hMPV-mediated lfTSLP induction, which
could be attributed to compromised NF-kappaB activation. Overall, these results
suggest that TBK1 may be instrumental for hMPV-mediated activation of NF-kappaB
downstream RIG-I and TLR3, leading to a specific induction of lfTSLP in hMPV
infected human airway cells.
PMID- 29343781
TI - Ocular and Clinical Characteristics Associated with the Extent of Posterior
Lamina Cribrosa Curve in Normal Tension Glaucoma.
AB - Although normal-tension glaucoma (NTG) is pathogenetically heterogenous, there
have been few attempts to subclassify NTG patients according to the mechanism and
anatomy of optic nerve damage. This cross-sectional study was performed to
investigate differences in the clinical and ocular characteristics between NTG
patient groups stratified according to the degree of posterior lamina cribrosa
(LC) curve which was assessed by calculating LC curvature index (LCCI). A total
of 101 eyes of 101 treatment naive NTG patients were included. The optic nerve
head was imaged using enhanced-depth-imaging spectral-domain optical coherence
tomography in three horizontal B-scan images in each eye. The patients were
divided into two groups based on the magnitude of LCCI using a cutoff of known
upper 95 percentile value in healthy subjects: a steeply curved LC group (Group
1, 75 eyes, 74.3%) and a relatively flat LC group (Group 2, 26 eyes, 25.7%). NTG
eyes with relatively flat LC had lower intraocular pressure, and were associated
with greater parapapillary structural alternation and systemic risk factors.
These data suggest that assessment of LC morphology may help clinicians seek
additional risk factors and make inferences about the mechanism of optic nerve
damage in individual patients.
PMID- 29343783
TI - The Hessian Blob Algorithm: Precise Particle Detection in Atomic Force Microscopy
Imagery.
AB - Imaging by atomic force microscopy (AFM) offers high-resolution descriptions of
many biological systems; however, regardless of resolution, conclusions drawn
from AFM images are only as robust as the analysis leading to those conclusions.
Vital to the analysis of biomolecules in AFM imagery is the initial detection of
individual particles from large-scale images. Threshold and watershed algorithms
are conventional for automatic particle detection but demand manual image
preprocessing and produce particle boundaries which deform as a function of user
defined parameters, producing imprecise results subject to bias. Here, we
introduce the Hessian blob to address these shortcomings. Combining a scale-space
framework with measures of local image curvature, the Hessian blob formally
defines particle centers and their boundaries, both to subpixel precision.
Resulting particle boundaries are independent of user defined parameters, with no
image preprocessing required. We demonstrate through direct comparison that the
Hessian blob algorithm more accurately detects biomolecules than conventional AFM
particle detection techniques. Furthermore, the algorithm proves largely
insensitive to common imaging artifacts and noise, delivering a stable framework
for particle analysis in AFM.
PMID- 29343782
TI - Protein phosphatase 5 regulates titin phosphorylation and function at a sarcomere
associated mechanosensor complex in cardiomyocytes.
AB - Serine/threonine protein phosphatase 5 (PP5) is ubiquitously expressed in
eukaryotic cells; however, its function in cardiomyocytes is unknown. Under basal
conditions, PP5 is autoinhibited, but enzymatic activity rises upon binding of
specific factors, such as the chaperone Hsp90. Here we show that PP5 binds and
dephosphorylates the elastic N2B-unique sequence (N2Bus) of titin in
cardiomyocytes. Using various binding and phosphorylation tests, cell-culture
manipulation, and transgenic mouse hearts, we demonstrate that PP5 associates
with N2Bus in vitro and in sarcomeres and is antagonistic to several protein
kinases, which phosphorylate N2Bus and lower titin-based passive tension. PP5 is
pathologically elevated and likely contributes to hypo-phosphorylation of N2Bus
in failing human hearts. Furthermore, Hsp90-activated PP5 interacts with
components of a sarcomeric, N2Bus-associated, mechanosensor complex, and blocks
mitogen-activated protein-kinase signaling in this complex. Our work establishes
PP5 as a compartmentalized, well-controlled phosphatase in cardiomyocytes, which
regulates titin properties and kinase signaling at the myofilaments.
PMID- 29343784
TI - Tensile stress effect on epitaxial BiFeO3 thin film grown on KTaO3.
AB - Comprehensive crystal structural study is performed for BiFeO3 (BFO) film grown
on KTaO3 (KTO) substrate using transmission electron microscopy (TEM) and x-ray
diffraction (XRD). Nano-beam electron diffraction (NBED) combined with structure
factor calculation and high resolution TEM images clearly reveal that the crystal
structure within BFO thin film is rhombohedral BFO, i.e., bulk BFO phase.
Epitaxial relationship found by NBED indicates the BFO film grows in a manner
that minimizes lattice mismatch with KTO. It further suggests BFO film is under
slight biaxial tensile stress (~0.35%) along in-plane direction. XRD reveals BFO
lattice is under compressive stress (~1.6%), along out-of-plane direction as a
result of the biaxial tensile strain applied along in-plane direction. This leads
to Poisson's ratio of ~0.68. In addition, we demonstrate (1) why hexagonal
notation rather than pseudocubic one is required for accurate BFO phase
evaluation and (2) a new XRD method that shows how rhombohedral BFO can readily
be identified among other phases by measuring a rhombohedral specific Bragg's
reflection.
PMID- 29343785
TI - A patient-specific lumped-parameter model of coronary circulation.
AB - A new lumped-parameter model for coronary hemodynamics is developed. This model
is developed for the whole coronary network based on CT scans of a patient
specific geometry including the right coronary tree, which is absent in many
previous mathematical models. The model adopts the structured tree model boundary
conditions similar to the work of Olufsen et al., thus avoiding the necessity of
invasive perfusion measurements. In addition, we also incorporated the effects of
the head loss at the two inlets of the large coronary arteries for the first
time. The head loss could explain the phenomenon of a sudden increase of the
resistance at the inlet of coronary vessel. The estimated blood pressure and flow
rate results from the model agree well with the clinical measurements. The
computed impedances also match the experimental perfusion measurement. The
effects of coronary arterial stenosis are considered and the fractional flow
reserve and relative flow in the coronary vessels for a stenotic vessel computed
in this model show good agreement with published experimental data. It is
believed that the approach could be readily translated to clinical practice to
facilitate real time clinical diagnosis.
PMID- 29343786
TI - AlGaInP Red LEDs with Hollow Hemispherical Polystyrene Arrays.
AB - A hollow hemispherical polystyrene (HHPS) was fabricated to reduce total internal
reflection in AlGaInP-based LEDs. At an injection current of 350 mA, the external
quantum efficiencies of LED-I, LED-II, LED-III, and LED-IV are 20.92%, 24.65%,
27.28%, and 33.77% and the wall-plug efficiencies are 17.11%, 20%, 22.5%, and
27.33%, respectively. The enhanced performance is attributed to the light output
power enhancement through the surface roughness, microlens-liked PS hemisphere,
and scatter-liked HHPS array. In this paper, the rigorous coupled wave analysis
(RCWA) numerical method was also conducted to demonstrate the HHPS array
effectively enlarge the effective light cone.
PMID- 29343787
TI - Author Correction: Comparison of bacterial microbiota of the predatory mite
Neoseiulus cucumeris (Acari: Phytoseiidae) and its factitious prey Tyrophagus
putrescentiae (Acari: Acaridae).
AB - A correction to this article has been published and is linked from the HTML
version of this paper. The error has been fixed in the paper.
PMID- 29343788
TI - Multiple losses of photosynthesis and convergent reductive genome evolution in
the colourless green algae Prototheca.
AB - Autotrophic eukaryotes have evolved by the endosymbiotic uptake of photosynthetic
organisms. Interestingly, many algae and plants have secondarily lost the
photosynthetic activity despite its great advantages. Prototheca and
Helicosporidium are non-photosynthetic green algae possessing colourless
plastids. The plastid genomes of Prototheca wickerhamii and Helicosporidium sp.
are highly reduced owing to the elimination of genes related to photosynthesis.
To gain further insight into the reductive genome evolution during the shift from
a photosynthetic to a heterotrophic lifestyle, we sequenced the plastid and
nuclear genomes of two Prototheca species, P. cutis JCM 15793 and P. stagnora JCM
9641, and performed comparative genome analyses among trebouxiophytes. Our
phylogenetic analyses using plastid- and nucleus-encoded proteins strongly
suggest that independent losses of photosynthesis have occurred at least three
times in the clade of Prototheca and Helicosporidium. Conserved gene content
among these non-photosynthetic lineages suggests that the plastid and nuclear
genomes have convergently eliminated a similar set of photosynthesis-related
genes. Other than the photosynthetic genes, significant gene loss and gain were
not observed in Prototheca compared to its closest photosynthetic relative
Auxenochlorella. Although it remains unclear why loss of photosynthesis occurred
in Prototheca, the mixotrophic capability of trebouxiophytes likely made it
possible to eliminate photosynthesis.
PMID- 29343789
TI - Three-dimensional migration behavior of juvenile salmonids in reservoirs and near
dams.
AB - To acquire 3-D tracking data on juvenile salmonids, Juvenile Salmon Acoustic
Telemetry System (JSATS) cabled hydrophone arrays were deployed in the forebays
of two dams on the Snake River and at a mid-reach reservoir between the dams. The
depth distributions of fish were estimated by statistical analyses performed on
large 3-D tracking data sets from ~33,500 individual acoustic tagged yearling and
subyearling Chinook salmon and juvenile steelhead at the two dams in 2012 and
subyearling Chinook salmon at the two dams and the mid-reach reservoir in 2013.
This research investigated the correlation between vertical migration behavior
and passage routes. The depth distributions of fish within the forebays of the
dams were significantly different from fish passing the mid-reach reservoir. Fish
residing deeper in the forebay tended to pass the dam using deeper powerhouse
routes. This difference in depth distributions indicated that the depth
distribution of fish at the mid-reach reservoir was not related to behaviors of
fish passing through certain routes of the adjacent dams. For fish that were
detected deeper than 17.5 m in the forebays, the probability of powerhouse
passage (i.e., turbine) increased significantly. Another important finding was
the variation in depth distributions during dam passage associated with the diel
period, especially the crepuscular periods.
PMID- 29343790
TI - Interference experiment with asymmetric double slit by using 1.2-MV field
emission transmission electron microscope.
AB - Advanced electron microscopy technologies have made it possible to perform
precise double-slit interference experiments. We used a 1.2-MV field emission
electron microscope providing coherent electron waves and a direct detection
camera system enabling single-electron detections at a sub-second exposure time.
We developed a method to perform the interference experiment by using an
asymmetric double-slit fabricated by a focused ion beam instrument and by
operating the microscope under a "pre-Fraunhofer" condition, different from the
Fraunhofer condition of conventional double-slit experiments. Here, pre
Fraunhofer condition means that each single-slit observation was performed under
the Fraunhofer condition, while the double-slit observations were performed under
the Fresnel condition. The interference experiments with each single slit and
with the asymmetric double slit were carried out under two different electron
dose conditions: high-dose for calculation of electron probability distribution
and low-dose for each single electron distribution. Finally, we exemplified the
distribution of single electrons by color-coding according to the above three
types of experiments as a composite image.
PMID- 29343791
TI - Single plasmid systems for inducible dual protein expression and for CRISPR
Cas9/CRISPRi gene regulation in lactic acid bacterium Lactococcus lactis.
AB - Lactococcus lactis is a food-grade lactic acid bacterium that is used in the
dairy industry as a cell factory and as a host for recombinant protein
expression. The nisin-controlled inducible expression (NICE) system is frequently
applied in L. lactis; however new tools for its genetic modification are highly
desirable. In this work NICE was adapted for dual protein expression. Plasmid
pNZDual, that contains two nisin promoters and multiple cloning sites (MCSs), and
pNZPolycist, that contains a single nisin promoter and two MCSs separated by the
ribosome binding site, were constructed. Genes for the infrared fluorescent
protein and for the human IgG-binding DARPin were cloned in all possible
combinations to assess the protein yield. The dual promoter plasmid pNZDual
enabled balanced expression of the two model proteins. It was exploited for the
development of a single-plasmid inducible CRISPR-Cas9 system (pNZCRISPR) by using
a nisin promoter, first to drive Cas9 expression and, secondly, to drive single
guide RNA transcription. sgRNAs against htrA and ermR directed Cas9 against
genomic or plasmid DNA and caused changes in bacterial growth and survival.
Replacing Cas9 by dCas9 enabled CRISPR interference-mediated silencing of the upp
gene. The present study introduces a new series of plasmids for advanced genetic
modification of lactic acid bacterium L. lactis.
PMID- 29343792
TI - Prebiotic formation of cyclic dipeptides under potentially early Earth
conditions.
AB - Cyclic dipeptides, also known as 2,5-diketopiperazines (DKPs), represent the
simplest peptides that were first completely characterized. DKPs can catalyze the
chiral selection of reactions and are considered as peptide precursors. The
origin of biochemical chirality and synthesis of peptides remains abstruse
problem believed to be essential precondition to origin of life. Therefore, it is
reasonable to believe that the DKPs could have played a key role in the origin of
life. How the formation of the DKPs through the condensation of unprotected amino
acids in simulated prebiotic conditions has been unclear. Herein, it was found
that cyclo-Pro-Pro could be formed directly from unprotected proline in the
aqueous solution of trimetaphosphate (P3m) under mild condition with the yield up
to 97%. Other amino acids were found to form proline-containing DKPs under the
same conditions in spite of lower yield. During the formation process of these
DKPs, P3m promotes the formation of linear dipeptides in the first step of the
mechanism. The above findings are helpful and significant for understanding the
formation of DKPs in the process of chemical evolution of life.
PMID- 29343793
TI - nNOS-positive minor-branches of the dorsal penile nerves is associated with
erectile function in the bilateral cavernous injury model of rats.
AB - The changes in neuronal nitric oxide synthases (nNOS) in the dorsal penile nerves
(DPNs) are consistent with cavernous nerve (CN) injury in rat models. However,
the anatomical relationship and morphological changes between the minor branches
of the DPNs and the CNs after injury have never been clearly explored. There were
forty 12 week old male Sprague-Dawley rats receiving bilateral cavernous nerve
injury (BCNI). Erectile function of intracavernous pressure and mean arterial
pressure were measured. The histology and ultrastructure with H&E stain, Masson's
trichrome stain and immunohistochemical stains were applied on the examination of
CNs and DPNs. We demonstrated communicating nerve branches between the DPNs and
the CNs in rats. The greatest damage and lowest erectile function were seen in
the 14th day and partially recovered in the 28th day after BCNI. The nNOS
positive DPN minor branches' number was significantly correlated with erectile
function. The sub-analysis of the number of nNOS positive DPN minor branches also
matched with the time course of the erectile function after BCNI. We suggest the
regeneration of the DPNs minor branches would ameliorate the erectile function in
BCNI rats.
PMID- 29343794
TI - Bone regeneration using a porcine bone substitute collagen composite in vitro and
in vivo.
AB - The biocharacteristics of xenogeneic grafts make them a possible substitute for
autogenous bone grafts in dental bone graft procedures. This study aimed to
develop a novel porcine graft with collagen capable of generating new bone in
bone defects via osteoconduction over 8 weeks of healing and to compare it with a
porcine graft. The porcine collagen graft was made to undergo a cell viability
test (MTT) and alkaline phosphatase assay (ALP). The surgical procedure was
performed in 20 male adult New Zealand white rabbits. Four calvarial critical
size defects of 6 mm in diameter were prepared in each rabbit. The upper left
defect was filled with a porcine graft of 500-1000 MUm, the upper right with a
porcine collagen graft, the lower left with hydroxyapatite/beta-tricalcium
phosphate and the lower right served as the control without any filling material.
The rabbits were divided and sacrificed at 2, 4, 6 and 8 weeks after surgery.
Histological and micro-CT scan results showed that the performance of the porcine
collagen graft is superior for regenerating new bone. Porcine collagen graft
showed cell viability and osteoblast-like cell differentiation in vitro. The
results indicate that porcine collagen graft is a potential bone substitute for
clinical application.
PMID- 29343795
TI - Recurrent wheezing in neonatal pneumonia is associated with combined infection
with Respiratory Syncytial Virus and Staphylococcus aureus or Klebsiella
pneumoniae.
AB - Both viral and bacterial infections can be associated with wheezing episodes in
children; however, information regarding combined infections with both viral and
bacterial pathogens in full term neonates is limited. We sought to investigate
the effects of viral-bacterial codetection on pneumonia severity and recurrent
wheezing. A retrospective cohort study was conducted on neonates admitted to our
hospital with pneumonia from 2009 to 2015. Of 606 total cases, 341 were diagnosed
with RSV only, and 265 were diagnosed with both RSV and a potential bacterial
pathogen. The leading four species of bacteria codetected with RSV were
Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Enterobacter
cloacae. Neonates with RSV and a potential bacterial pathogen were significantly
more likely to have worse symptoms, higher C-reactive protein values and more
abnormal chest x-ray manifestations with Bonferroni correction for multiple
comparisons (P < 0.01). On Cox regression analysis, an increased risk of
recurrent wheezing was found for neonates positive for RSV-Staphylococcus aureus
and RSV-Klebsiella pneumoniae. Our findings indicate that the combination of
bacteria and RSV in the neonatal airway is associated with more serious clinical
characteristics. The presence of RSV and Staphylococcus aureus or Klebsiella
pneumoniae may provide predictive markers for wheeze.
PMID- 29343796
TI - Integrated climate-chemical indicators of diffuse pollution from land to water.
AB - Management of agricultural diffuse pollution to water remains a challenge and is
influenced by the complex interactions of rainfall-runoff pathways, soil and
nutrient management, agricultural landscape heterogeneity and biogeochemical
cycling in receiving water bodies. Amplified cycles of weather can also influence
nutrient loss to water although they are less considered in policy reviews. Here,
we present the development of climate-chemical indicators of diffuse pollution in
highly monitored catchments in Western Europe. Specifically, we investigated the
influences and relationships between weather processes amplified by the North
Atlantic Oscillation during a sharp upward trend (2010-2016) and the patterns of
diffuse nitrate and phosphorus pollution in rivers. On an annual scale, we found
correlations between local catchment-scale nutrient concentrations in rivers and
the influence of larger, oceanic-scale climate patterns defined by the intensity
of the North Atlantic Oscillation. These influences were catchment-specific
showing positive, negative or no correlation according to a typology. Upward
trends in these decadal oscillations may override positive benefits of local
management in some years or indicate greater benefits in other years. Developing
integrated climate-chemical indicators into catchment monitoring indicators will
provide a new and important contribution to water quality management objectives.
PMID- 29343797
TI - Artificial Intelligence Estimation of Carotid-Femoral Pulse Wave Velocity using
Carotid Waveform.
AB - In this article, we offer an artificial intelligence method to estimate the
carotid-femoral Pulse Wave Velocity (PWV) non-invasively from one uncalibrated
carotid waveform measured by tonometry and few routine clinical variables. Since
the signal processing inputs to this machine learning algorithm are sensor
agnostic, the presented method can accompany any medical instrument that provides
a calibrated or uncalibrated carotid pressure waveform. Our results show that,
for an unseen hold back test set population in the age range of 20 to 69, our
model can estimate PWV with a Root-Mean-Square Error (RMSE) of 1.12 m/sec
compared to the reference method. The results convey the fact that this model is
a reliable surrogate of PWV. Our study also showed that estimated PWV was
significantly associated with an increased risk of CVDs.
PMID- 29343799
TI - Publisher Correction: Bacillus SEVA siblings: A Golden Gate-based toolbox to
create personalized integrative vectors for Bacillus subtilis.
AB - A correction to this article has been published and is linked from the HTML
version of this paper. The error has been fixed in the paper.
PMID- 29343798
TI - Structural and functional insights into S-thiolation of human serum albumins.
AB - Human serum albumin (HSA) is the most abundant serum protein, contributing to the
maintenance of redox balance in the extracellular fluids. One single free
cysteine residue at position 34 is believed to be a target of oxidation. However,
the molecular details and functions of oxidized HSAs remain obscure. Here we
analyzed serum samples from normal subjects and hyperlipidemia patients and
observed an enhanced S-thiolation of HSA in the hyperlipidemia patients as
compared to the control individuals. Both cysteine and homocysteine were
identified as the low molecular weight thiols bound to the HSAs. Intriguingly, S
thiolations were observed not only at Cys34, but also at multiple cysteine
residues in the disulfide bonds of HSA. When the serum albumins from genetically
modified mice that exhibit high levels of total homocysteine in serum were
analyzed, we observed an enhanced S-homocysteinylation at multiple cysteine
residues. In addition, the cysteine residues in the disulfide bonds were also
thiolated in recombinant HSA that had been treated with the disulfide molecules.
These findings and the result that S-homocysteinylation mediated increased
surface hydrophobicity and ligand binding activity of HSA offer new insights into
structural and functional alternation of serum albumins via S-thiolation.
PMID- 29343800
TI - Faecal shedding of rotavirus vaccine in Chinese children after vaccination with
Lanzhou lamb rotavirus vaccine.
AB - Lanzhou lamb rotavirus vaccine (LLR) is an oral live attenuated vaccine first
licensed in China in 2000. To date, > 60 million doses of LLR have been
distributed to children. However, very little is known about faecal shedding of
LLR in children. Therefore, faecal samples (n = 1,184) were collected from 114
children for 15 days post-vaccination in September-November 2011/2012. Faecal
shedding and viral loads were determined by an enzyme immunoassay kit (EIA) and
real-time RT-PCR. The complete genome was sequenced and the vaccine strain was
isolated by culture in MA104 cells. Approximately 14.0% (16/114) of children had
rotavirus-positive samples by EIA for at least 1 day post-vaccination. Viral
loads in EIA-positive samples ranged from < 1.0 * 103 to 1.9 * 108 copies/g.
Faecal shedding occurred as early as post-vaccination day 2 and as late as post
vaccination day 13 and peaked on post-vaccination day 5-10. One LLR strain was
isolated by culture in MA104 cells. Sequence analysis showed 99% identity with
LLR prototype strain. Faecal shedding of LLR in stool is common within 15 days of
LLR vaccination, indicating vaccine strains can replicate in human enteric
tissues.
PMID- 29343801
TI - Dictionary learning-based reverberation removal enables depth-resolved
photoacoustic microscopy of cortical microvasculature in the mouse brain.
AB - Photoacoustic microscopy (PAM) capitalizes on the optical absorption of blood
hemoglobin to enable label-free high-contrast imaging of the cerebral
microvasculature in vivo. Although time-resolved ultrasonic detection equips PAM
with depth-sectioning capability, most of the data at depths are often obscured
by acoustic reverberant artifacts from superficial cortical layers and thus
unusable. In this paper, we present a first-of-a-kind dictionary learning
algorithm to remove the reverberant signal while preserving underlying
microvascular anatomy. This algorithm was validated in vitro, using dyed beads
embedded in an optically transparent polydimethylsiloxane phantom. Subsequently,
we demonstrated in the live mouse brain that the algorithm can suppress
reverberant artifacts by 21.0 +/- 5.4 dB, enabling depth-resolved PAM up to 500
um from the brain surface.
PMID- 29343802
TI - Loss induced coherent combining in InP-Si3N4 hybrid platform.
AB - Loss, as a time-reversed counterpart of gain, can also be used to control lasing
in an optical system with coupled cavities. In this study, by manipulating mirror
losses at different output ports of coupled Fabry-Perot cavities, an integrated
coherently combined laser system is proposed and experimentally demonstrated in
the InP-Si3N4 hybrid platform. Two InP-based reflective semiconductor amplifiers
are coherently combined through an adiabatic 50:50 directional coupler in silicon
nitride. The combining efficiency is ~92% at ~2* threshold. The novel system not
only realizes the miniaturization of coherent laser beam combining but also
provides a chip-scale platform to study the coherent coupling between coupled
laser cavities.
PMID- 29343803
TI - Targeted next generation sequencing in a young population with suspected
inherited malignant cardiac arrhythmias.
AB - Aborted sudden cardiac death in the young often is due to inherited heart
disease. However, the clinical phenotype in these patients is not always evident.
The aim of this study was to identify pathogenic molecular genetic variants in a
population with suspected inherited cardiac arrhythmias. Eligible patients were
admitted to Aarhus University Hospital, Denmark during the period 1999-2013 with
arrhythmias assumed caused by a hereditary heart disease, and in whom no genotype
had been established. We used the Danish national pacemaker and ICD registry to
identify this cohort. One third (24/80) of the study population had first-line
genetic testing with a targeted next-generation sequencing (NGS) panel, and two
third (56/80) of the study population had second-line genetic testing with NGS
where prior Sanger sequencing did not reveal a causative variant. Variants were
assessed according to the American College of Medical Genetics and Genomics
(ACMG) guidelines. We included 80 patients. Median age (IQR) was 38 (28-43)
years, 54 (68%) were males. First-line genetic testing identified a genetic
variant in 33% (8/24) of the cases and second-line genetic testing revealed a
variant in 20% (11/56) of the cases. Eleven variants were considered pathogenic,
three likely pathogenic and 10 were variants of unknown significance (VUS).
Seventeen variants were very rare with a minor allele frequency (MAF) <=0.02% in
all population databases used in the study. Molecular genetic testing of patients
with suspected inherited cardiac arrhythmias with NGS identifies a molecular
genetic cause in a significant proportion of patients.
PMID- 29343804
TI - Compound heterozygous SPATA5 variants in four families and functional studies of
SPATA5 deficiency.
AB - Variants in the SPATA5 gene were recently described in a cohort of patients with
global developmental delay, sensorineural hearing loss, seizures, cortical visual
impairment and microcephaly. SPATA5 protein localizes predominantly in the
mitochondria and is proposed to be involved in mitochondrial function and brain
developmental processes. However no functional studies have been performed. This
study describes five patients with psychomotor developmental delay, microcephaly,
epilepsy and hearing impairment, who were thought clinically to have a
mitochondrial disease with subsequent whole-exome sequencing analysis detecting
compound heterozygous variants in the SPATA5 gene. A summary of clinical data of
all the SPATA5 patients reported in the literature confirms the characteristic
phenotype. To assess SPATA5's role in mitochondrial dynamics, functional studies
were performed on rat cortical neurons. SPATA5-deficient neurons had a
significant imbalance in the mitochondrial fusion-fission rate, impaired energy
production and short axons. In conclusion, SPATA5 protein has an important role
in mitochondrial dynamics and axonal growth. Biallelic variants in the SPATA5
gene can affect mitochondria in cortical neurons and should be considered in
patients with a neurodegenerative disorder and/or with clinical presentation
resembling a mitochondrial disorder.
PMID- 29343806
TI - Effect of light-delignification on mechanical, hydrophobic, and thermal
properties of high-strength molded fiber materials.
AB - This study developed a high-strength molded fiber material (HMFM) using pulp
fibers, which could be a good substitute for plastic and solid wood materials.
The surface composition, microstructure and thermal properties of HMFM were
investigated by XPS, SEM and DSC, respectively. The SEM observations showed that
the obvious adhesive substances and agglomeration appeared among fibers, and the
inter-fiber contact area and binding tightness increased after the light
delignification. The XPS examination showed that the oxygen-rich composition on
the outer surface of HMFM were reduced, and the outer surface coverage of lignin
increased from 70.05% to 90.15% after the light-delignification. The DSC
observation showed that the thermal stability of HMFM decreased, the temperature
for the maximum rate of mass loss decreased from 370 degrees C to 345.6 degrees
C, and the enthalpy value required for decomposition was reduced from 110.8 J/g
to 68.0 J/g after the light-delignification. The mechanical and hydrophobic
properties of HMFM were obviously improved after the light-delignification. When
the content of lignin decreased from 24.9% to 11.45%, the density of HMFM
increased by 6.0%, the tensile strength increased by 22.0%, the bending strength
increased by 23.9%, and the water contact angle increased from 64.3 degrees -72.7
degrees to 80.8 degrees -84.3 degrees .
PMID- 29343805
TI - Biallelic variants in KIF14 cause intellectual disability with microcephaly.
AB - Kinesin proteins are critical for various cellular functions such as
intracellular transport and cell division, and many members of the family have
been linked to monogenic disorders and cancer. We report eight individuals with
intellectual disability and microcephaly from four unrelated families with
parental consanguinity. In the affected individuals of each family, homozygosity
for likely pathogenic variants in KIF14 were detected; two loss-of-function
(p.Asn83Ilefs*3 and p.Ser1478fs), and two missense substitutions (p.Ser841Phe and
p.Gly459Arg). KIF14 is a mitotic motor protein that is required for spindle
localization of the mitotic citron rho-interacting kinase, CIT, also mutated in
microcephaly. Our results demonstrate the involvement of KIF14 in development and
reveal a wide phenotypic variability ranging from fetal lethality to moderate
developmental delay and microcephaly.
PMID- 29343807
TI - House dust mite induced allergic airway disease is attenuated in CD11ccreIL
4Ralpha-/l degrees x mice.
AB - The precise mechanisms leading to development of T helper type (Th)2-driven
allergic responses are unknown. We aimed to determine how IL-4 receptor alpha (IL
4Ralpha) signaling on CD11c+ cells influences allergen-induced Th2 responses in
mice. CD11ccreIL-4Ralpha-/l degrees x mice, deficient in IL-4Ralpha on dendritic
cells and alveolar macrophages, were compared to IL-4Ralpha-/l degrees x
littermate controls in models of allergic airway disease induced by OVA/alum, OVA
alone or house dust mite. Cytokine responses, eosinophil and neutrophil
infiltration into the lungs, airway hyperreactivity and mucus hypersecretion were
evaluated after allergen challenge. In the OVA/alum model, CD11ccreIL-4Ralpha
/lox mice had similar airway hyperreactivity, eosinophil infiltration, Th2-type
cytokine production and mucus hypersecretion to littermate controls. When alum
was omitted during sensitization, CD11ccreIL-4Ralpha-/lox mice had similar airway
hyperreactivity and mucus secretion but reduced Th2-type cytokine production and
eosinophils, suggesting alum overrides the requirement for IL-4Ralpha signaling
on CD11c+ cells in enhancing Th2-type responses. In the house dust mite model,
CD11ccreIL-4Ralpha-/lox mice showed similar mucus secretion, but reduced Th2
responses, eosinophils, neutrophils and airway hyperreactivity, unlike previously
tested LysMcreIL-4Ralpha-/lox mice, which lack IL-4Ralpha on alveolar macrophages
but not on dendritic cells. Therefore, our results indicate that IL-4Ralpha
signaling on dendritic cells promotes allergen-induced Th2 responses and
eosinophil infiltration into the lung.
PMID- 29343808
TI - Stereotactic topography of the greater and third occipital nerves and its
clinical implication.
AB - This study aimed to provide topographic information of the greater occipital
(GON) and third occipital (3ON) nerves, with the three-dimensional locations of
their emerging points on the back muscles (60 sides, 30 cadavers) and their
spatial relationship with muscle layers, using a 3D digitizer (Microscribe G2X,
Immersion Corp, San Jose CA, USA). With reference to the external occipital
protuberance (EOP), GON pierced the trapezius at a point 22.6 +/- 7.4 mm lateral
and 16.3 +/- 5.9 mm inferior and the semispinalis capitis (SSC) at a point 13.1
+/- 6.0 mm lateral and 27.7 +/- 9.9 mm inferior. With the same reference, 3ON
pierced, the trapezius at a point 12.9 +/- 9.3 mm lateral and 44.2 +/- 21.4 mm
inferior, the splenius capitis at a point 10.0 +/- 5.3 mm lateral and 59.2 +/-
19.8 mm inferior, and SSC at a point 11.5 +/- 9.9 mm lateral and 61.4 +/- 15.3 mm
inferior. Additionally, GON arose, winding up the obliquus capitis inferior, with
the winding point located 52.3 +/- 11.7 mm inferior to EOP and 30.2 +/- 8.9 mm
lateral to the midsagittal line. Knowing the course of GON and 3ON, from their
emergence between vertebrae to the subcutaneous layer, is necessary for reliable
nerve detection and precise analgesic injections. Moreover, stereotactic
measurement using the 3D digitizer seems useful and accurate for neurovascular
structure study.
PMID- 29343809
TI - Interaction of smoking and metabolic syndrome in increasing the recurrence risk
of colorectal cancer in a Chinese male cohort: a retrospective study.
AB - Whether smoking and metabolic syndrome (MetS) can affect colorectal carcinoma
(CRC) prognosis remains debatable. Therefore, the present study aimed to examine
the individual and combined effects of smoking and MetS on the prognosis of
patients with localized CRC, including stage I to III disease. The relationship
among smoking status, MetS, and CRC was assessed in 838 Chinese male patients.
Cox proportional hazards regression analysis was used to evaluate CRC prognosis
adjusted for clinicopathological variables. Relative excess risk of interaction
(RERI), attributable proportion (AP), and synergy index (SI) were used to
evaluate additive interactions between smoking and MetS. The presence of MetS was
an independent risk factor for low rates of recurrence-free survival (RFS) but
not for overall survival (OS). However, smoking was independently associated with
both poor RFS and OS. Furthermore, the recurrence risk for current smokers with
MetS was 1.62 times as high as the sum of risks in patients exposed to each risk
factor alone. In conclusion, current smoking habit is a risk factor for both
recurrence and cancer-specific mortality in CRC patients, while MetS is an
independent predictor for CRC recurrence. Furthermore, these two factors have an
additive effect on the recurrence risk of CRC.
PMID- 29343810
TI - Mitochondrial DNA damage and subsequent activation of Z-DNA binding protein 1
links oxidative stress to inflammation in epithelial cells.
AB - This report identifies mitochondrial DNA (mtDNA) as a target and active mediator
that links low-level oxidative stress to inflammatory response in pulmonary
epithelial cells. Extrusion of mtDNA into the bronchoalveolar lavage fluid occurs
as an early event in mice subjected to cigarette smoke injury, concomitantly with
the depletion of mtDNA in the lung tissue. In cultured lung epithelial cells,
prolonged, low-level oxidative stress damages the mtDNA, without any detectable
damage to the nuclear DNA. In turn, cellular depletion of the mtDNA occurs,
together with a transient remodeling of cellular bioenergetics and morphology -
all without any detectable impairment in overall cell viability. Damaged mtDNA
first enters the cytoplasm, where it binds to Z-DNA binding protein 1 (ZBP1) and
triggers inflammation via the TANK-binding kinase 1 /interferon regulatory factor
3 signaling pathway. Fragments of the mtDNA are subsequently released into the
extracellular space via exosomes. MtDNA-containing exosomes are capable of
inducing an inflammatory response in naive (non-oxidatively stressed) epithelial
cells. In vivo, administration of isolated mtDNA into the in lungs of naive mice
induces the production of pro-inflammatory mediators, without histopathologic
evidence of tissue injury. We propose that mtDNA-specific damage, and subsequent
activation of the ZBP1 pathway, is a mechanism that links prolonged, low-level
oxidative stress to autocrine and paracrine inflammation during the early stages
of inflammatory lung disease.
PMID- 29343812
TI - High albumin level is a predictor of favorable response to immunotherapy in
autoimmune encephalitis.
AB - There is no known biomarker that predicts the response to immune therapy in
autoimmune synaptic encephalitis. Thus, we investigated serum albumin as a
prognostic biomarker of early immune therapies in patients with autoimmune
encephalitis. We enrolled patients who were diagnosed with definite autoimmune
encephalitis and underwent IVIg treatment at Seoul National University Hospital
from 2012 to 2017. Patients were dichotomized according to serum albumin prior to
IVIg administration with a cut-off level of 4.0 g/dL, which was the median value
of 50% of patients. Seventeen (53.1%) of the 32 patients with definite autoimmune
encephalitis who received IVIg treatment in our hospital had low serum albumin
(<4.0 g/dL). The initial disease severity (mRS >= 4) was the sole factor that
predicted low albumin in autoimmune encephalitis patients using multivariate
analysis (P = 0.013). The low albumin group exhibited a worse response to immune
therapy at the third and fourth weeks from IVIg administration (P < 0.01 and P =
0.012, respectively), and recovery to activities of daily life without assistance
was faster in the high albumin group (log-rank test for trend, P < 0.01). Our
study found that pretreatment low serum albumin was a significant indicator of
autoimmune encephalitis prognosis in the short-term and long-term.
PMID- 29343811
TI - A procession of metabolic alterations accompanying muscle senescence in Manduca
sexta.
AB - Biological aging profoundly impairs muscle function, performance, and metabolism.
Because the progression of metabolic alterations associated with aging muscle has
not been chronicled, we tracked the metabolic profiles of flight muscle from
middle to advanced age in Manduca sexta to identify key molecules during the
progression of muscle aging, as well as to evaluate the utility of the M. sexta
system for molecular dissection of muscle aging. We identified a number of
differences between Diel Time, Sexes, and Muscle Ages, including changes in
metabolites related to energetics, extracellular matrix turnover, and glutathione
metabolism. Increased abundances of glycolytic metabolites suggest a shift toward
increased glycolysis with advancing age, whereas decreased abundances in
lysolipids and acylcarnitines reflect decreasing beta-oxidation. We also observed
a shift towards decreased polyamine metabolism with age, which might result in an
age-related decline in lipid metabolism possibly due to regulation of energy
metabolism by polyamines. Collectively, our findings demonstrate the feasibility
of our system and approach and provide a deeper understanding of lepidopteran
aging. More importantly, the results identify the key altered metabolic pathways
that collectively contribute to the muscle aging phenotype and thereby improve
our understanding of muscle senescence.
PMID- 29343813
TI - The Drosophila Gr28bD product is a non-specific cation channel that can be used
as a novel thermogenetic tool.
AB - Extrinsic control of single neurons and neuronal populations is a powerful
approach for understanding how neural circuits function. Adding new thermogenetic
tools to existing optogenetic and other forms of intervention will increase the
complexity of questions that can be addressed. A good candidate for developing
new thermogenetic tools is the Drosophila gustatory receptor family, which has
been implicated in high-temperature avoidance behavior. We examined the five
members of the Gr28b gene cluster for temperature-dependent properties via three
approaches: biophysical characterization in Xenopus oocytes, functional calcium
imaging in Drosophila motor neurons, and behavioral assays in adult Drosophila.
Our results show that Gr28bD expression in Xenopus oocytes produces a non
specific cationic current that is activated by elevated temperatures. This
current is non-inactivating and non-voltage dependent. When expressed in
Drosophila motor neurons, Gr28bD can be used to change the firing pattern of
individual cells in a temperature-dependent fashion. Finally, we show that pan
neuronal or motor neuron expression of Gr28bD can be used to alter fruit fly
behavior with elevated temperatures. Together, these results validate the
potential of the Gr28bD gene as a founding member of a new class of thermogenetic
tools.
PMID- 29343814
TI - Intrinsic apoptotic pathway activation increases response to anti-estrogens in
luminal breast cancers.
AB - Estrogen receptor-alpha positive (ERalpha+) breast cancer accounts for
approximately 70-80% of the nearly 25,0000 new cases of breast cancer diagnosed
in the US each year. Endocrine-targeted therapies (those that block ERalpha
activity) serve as the first line of treatment in most cases. Despite the proven
benefit of endocrine therapies, however, ERalpha+ breast tumors can develop
resistance to endocrine therapy, causing disease progression or relapse,
particularly in the metastatic setting. Anti-apoptotic Bcl-2 family proteins
enhance breast tumor cell survival, often promoting resistance to targeted
therapies, including endocrine therapies. Herein, we investigated whether
blockade of anti-apoptotic Bcl-2 family proteins could sensitize luminal breast
cancers to anti-estrogen treatment. We used long-term estrogen deprivation (LTED)
of human ERalpha+ breast cancer cell lines, an established model of sustained
treatment with and acquired resistance to aromatase inhibitors (AIs), in
combination with Bcl-2/Bcl-xL inhibition (ABT-263), finding that ABT-263 induced
only limited tumor cell killing in LTED-selected cells in culture and in vivo.
Interestingly, expression and activity of the Bcl-2-related factor Mcl-1 was
increased in LTED cells. Genetic Mcl-1 ablation induced apoptosis in LTED
selected cells, and potently increased their sensitivity to ABT-263. Increased
expression and activity of Mcl-1 was similarly seen in clinical breast tumor
specimens treated with AI + the selective estrogen receptor downregulator
fulvestrant. Delivery of Mcl-1 siRNA loaded into polymeric nanoparticles (MCL1 si
NPs) decreased Mcl-1 expression in LTED-selected and fulvestrant-treated cells,
increasing tumor cell death and blocking tumor cell growth. These findings
suggest that Mcl-1 upregulation in response to anti-estrogen treatment enhances
tumor cell survival, decreasing response to therapeutic treatments. Therefore,
strategies blocking Mcl-1 expression or activity used in combination with
endocrine therapies would enhance tumor cell death.
PMID- 29343816
TI - Sclerotic bone lesions as a potential imaging biomarker for the diagnosis of
tuberous sclerosis complex.
AB - Tuberous-sclerosis-complex (TSC) is associated with a high lifetime risk of
severe complications. Clinical manifestations are largely variable and diagnosis
is often missed. Sclerotic-bone-lesions (SBL) could represent a potential imaging
biomarker for the diagnosis of TSC. In this study, computed tomography (CT) data
sets of 49 TSC patients (31 females) were included and compared to an age/sex
matched control group. Imaging features of SBLs included frequency, size and
location pattern. Sensitivities, specificities and cutoff values for the
diagnosis of TSC were established for the skull, thorax, and abdomen/pelvis. In
TSC patients, 3439 SBLs were detected, including 665 skull SBLs, 1426 thoracal
SBLs and 1348 abdominal/pelvic SBLs. In the matched control-collective, 157 SBLs
could be found. The frequency of SBLs enabled a reliable differentiation between
TSC patients and the control collective with the following sensitivities and
specificities. Skull: >=5 SBLs, 0.783, 1; thorax: >=4 SBLs, 0.967, 0.967;
abdomen/pelvis: >=5 SBLs: 0.938, 0.906. SBL size was significantly larger
compared to controls (p < 0.05). Based on the frequency, size and location
pattern of SBLs TSC can be suspected. SBLs may serve as a potential imaging
biomarker in the workup of TSC patients.
PMID- 29343815
TI - MicroRNA-145-5p and microRNA-320a encapsulated in endothelial microparticles
contribute to the progression of vasculitis in acute Kawasaki Disease.
AB - Kawasaki Disease (KD) is an acute inflammatory disease that takes the form of
systemic vasculitis. Endothelial microparticles (EMPs) have been recognized as an
important transcellular delivery system. We hypothesized whether EMPs are
involved in vasculitis in acute KD. Fifty patients with acute KD were enrolled,
divided into two subgroups: those with coronary artery lesions (CAL) (n = 5) and
those without CAL (NCAL) (n = 45). EMPs were measured using flow cytometry, and
microRNA (miR) expression profiling was performed by microRNA array. The
percentage of EMPs in acute KD was significantly higher than in controls (P <
0.0001). EMPs in patients with CAL rapidly increased after the initial treatment,
and was significantly higher than those in NCAL (P < 0.001). In patients with
CAL, we identified 2 specific miRs encapsulated in EMPs, hsa-miR-145-5p and hsa
miR-320a, which are predicted to affect monocyte function using in silico
analysis, and were demonstrated to upregulate inflammatory cytokine mRNAs in THP
1 monocytes. In situ hybridization confirmed that hsa-miR-145-5p was
preferentially expressed in CAL. EMPs may serve as a sensitive marker for the
severity of vasculitis in acute KD. Moreover, these 2 specific miRs encapsulated
in EMPs might be involved in inflammatory cytokine regulation and the
pathogenesis of vasculitis in acute KD.
PMID- 29343817
TI - Associations between body mass index and the risk of renal events in patients
with type 2 diabetes.
AB - BACKGROUND/OBJECTIVES: We aimed to evaluate the relationship between BMI and the
risk of renal disease in patients with type 2 diabetes in the Action in Diabetes
and Vascular Disease: PreterAx and DiamicroN Modified-Release Controlled
Evaluation (ADVANCE) study. SUBJECTS/METHODS: Participants were divided into six
baseline BMI categories: <18.5 (underweight, n = 58); >=18.5 to <25 (normal, n =
2894); >=25 to <30 (overweight, n = 4340); >=30 to <35 (obesity grade 1, n =
2265); >=35 to <40 (obesity grade 2, n = 744); and >=40 kg/m2 (obesity grade 3, n
= 294); those underweight were excluded. The composite outcome "major renal
event" was defined as development of new macroalbuminuria, doubling of
creatinine, end stage renal disease, or renal death. These outcomes and
development of new microalbuminuria were considered individually as secondary
endpoints. RESULTS: During 5-years of follow-up, major renal events occurred in
487 (4.6%) patients. The risk increased with higher BMI. Multivariable-adjusted
HRs (95% CIs), compared to normal weight, were: 0.91 (0.72-1.15) for overweight;
1.03 (0.77-1.37) for obesity grade 1; 1.42 (0.98-2.07) for grade 2; and 2.16
(1.34-3.48) for grade 3 (p for trend = 0.006). These findings were similar across
subgroups by randomised interventions (intensive versus standard glucose control
and perindopril-indapamide versus placebo). Every additional unit of BMI over 25
kg/m2 increased the risk of major renal events by 4 (1-6)%. Comparable results
were observed with the risk of secondary endpoints. CONCLUSIONS: Higher BMI is an
independent predictor of major renal events in patients with type 2 diabetes. Our
findings encourage weight loss to improve nephroprotection in these patients.
PMID- 29343818
TI - A surfactant polymer dressing potentiates antimicrobial efficacy in biofilm
disruption.
AB - A 100% water-soluble surfactant polymer dressing (SPD) that is bio-compatible and
non-ionic has been reported to improve wound closure in preliminary clinical
studies. The mechanism of action of SPD in wound healing remains unclear. Biofilm
infection is a significant problem that hinders proper wound closure. The
objective of this study was to characterize the mechanism of action of SPD
inhibition of bacterial biofilm development. Static biofilms (48 h) of the
primary wound pathogens Pseudomonas aeruginosa (PA01), Staphylococcus aureus
(USA300) were grown on polycarbonate membranes and treated with SPD with and
without antibiotics for an additional 24 h. The standard antibiotics - tobramycin
(10 MUg/ml) for PA01 and rifampicin (10 MUg/ml) for USA300, were used in these
studies. Following 24 h treatment with and without antibiotics, the biofilms were
characterized using scanning electron microscopy (SEM) structural imaging, in
vitro imaging system (IVIS) proliferation imaging, colony forming units (CFU),
viability assay, quantitative PCR (qPCR) for virulence gene expression. Because
SPD is a surfactant based dressing, it potentially has a direct effect on Gram
negative bacteria such as Pseudomonas primarily due to the lipid-based outer
membrane of the bacteria. SPD is a surfactant based dressing that has potent anti
biofilm properties directly or in synergy with antibiotics.
PMID- 29343819
TI - Effects of silver nanocolloids on plant complex type N-glycans in Oryza sativa
roots.
AB - Silver nanomaterials have been mainly developed as antibacterial healthcare
products worldwide, because of their antibacterial activity. However, there is
little data regarding the potential risks and effects of large amounts of silver
nanomaterials on plants. In contrast, N-glycans play important roles in various
biological phenomena, and their structures and expressions are sensitive to
ambient environmental changes. Therefore, to assesse the effects of silver
nanomaterials, we focused on the correlation between N-glycans and the effects of
silver nanomaterials in plants and analyzed N-glycan structures in Oryza sativa
seedlings exposed to silver nanocolloids (SNCs). The phenotype analysis showed
that the shoot was not affected by any SNC concentrations, whereas the high SNC
exposed root was seriously damaged. Therefore, we performed comparative N-glycan
analysis of roots. As a result, five of total N-glycans were significantly
increased in SNC exposed roots, of which one was a free-N-glycan with one beta-N
acetylglucosamine residue at the reducing end. Our results suggest that the
transition of plant complex type N-glycans, including free-N-glycans, was caused
by abnormalities in O. sativa development, and free-N-glycan itself has an
important role in plant development. This study originally adapted glycome
transition analysis to environmental toxicology and proposed a new category
called "Environmental glycobiology".
PMID- 29343820
TI - Increased left ventricular mass index is present in patients with type 2 diabetes
without ischemic heart disease.
AB - Left ventricular mass index (LVMI) increase has been described in hypertension
(HTN), but less is known about its association with type 2 diabetes (T2DM). As
these conditions frequently co-exist, we investigated the association of T2DM,
HTN and both with echocardiographic parameters, and hypothesized that patients
with both had highest LVMI, followed by patients with only T2DM or HTN. Study
population included 101 T2DM patients, 62 patients with HTN and no T2DM, and 76
patients with T2DM and HTN, excluded for ischemic heart disease. Demographic and
clinical data, biochemical measurements, stress echocardiography, transthoracic
2D Doppler and tissue Doppler echocardiography were performed. Multivariable
logistic regression was used to determine the independent association with T2DM.
Linear regression models and Pearson's correlation were used to assess the
correlations between LVMI and other parameters. Patients with only T2DM had
significantly greater LVMI (84.9 +/- 20.3 g/m2) compared to patients with T2DM
and HTN (77.9 +/- 16 g/m2) and only HTN (69.8 +/- 12.4 g/m2). In multivariate
logistic regression analysis, T2DM was associated with LVMI (OR 1.033, 95%CI
1.003-1.065, p = 0.029). A positive correlation of LVMI was found with fasting
glucose (p < 0.001) and HbA1c (p = 0.0003). Increased LVMI could be a potential,
pre-symptomatic marker of myocardial structural change in T2DM.
PMID- 29343821
TI - Focal hyperintensity in the dorsal brain stem of patients with cerebellopontine
angle tumor: A high-resolution 3 T MRI study.
AB - Focal hyperintensity (FHI) in the dorsal brain stem on T2-weighted images of
patients with cerebellopontine angle (CPA) tumor was thought to indicate
degeneration of the vestibular nucleus and to be specific to vestibular
schwannoma. The purpose of this study was to evaluate FHI by using high
resolution 3 Tesla magnetic resonance imaging (3 T MRI) and the relation to
clinical characteristics. We retrospectively reviewed the clinical data and MRI
of 45 patients with CPA tumors (34 vestibular schwannomas and 11 other tumors).
FHI in the dorsal brain stem was found in 25 (55.6%) patients (20 vestibular
schwannomas and 5 other tumors). For the vestibular schwannomas, the factors
contributing to positive FHI were age (p = 0.025), max CPA (p = < 0.001),
hearing ability (P = 0.005), and canal paresis (p = < 0.001) in the univariate
analysis. Multivariate regression analysis showed that max CPA (p = 0.029) was a
significant factor of positive FHI. In other CPA tumors, these factors were not
significant predictors. With the use of 3 T MRI, FHI was observed more frequently
than previously reported. Our results suggest that FHI is not a specific
indicator of vestibular schwannoma and is related to not only vestibular function
but also other factors.
PMID- 29343823
TI - Methods and extractants to evaluate silicon availability for sugarcane.
AB - The correct evaluation of silicon (Si) availability in different soil types is
critical in defining the amount of Si to be supplied to crops. This study was
carried out to evaluate two methods and five chemical Si extractants in clayey,
sandy-loam, and sandy soils cultivated with sugarcane (Saccharum spp. hybrids).
Soluble Si was extracted using two extraction methods (conventional and microwave
oven) and five Si extractants (CaCl2, deionized water, KCl, Na-acetate buffer (pH
4.0), and acetic acid). No single method and/or extractant adequately estimated
the Si availability in the soils. Conventional extraction with KCl was no more
effective than other methods in evaluating Si availability; however, it had less
variation in estimating soluble Si between soils with different textural classes.
In the clayey and sandy soils, the Na-acetate buffer (pH 4.0) and acetic acid
were effective in evaluating the Si availability in the soil regardless of the
extraction methods. The extraction with acetic acid using the microwave oven,
however, overestimated the Si availability. In the sandy-loam soil, extraction
with deionized water using the microwave oven method was more effective in
estimating the Si availability in the soil than the other extraction methods.
PMID- 29343822
TI - The MICALs are a Family of F-actin Dismantling Oxidoreductases Conserved from
Drosophila to Humans.
AB - Cellular form and function - and thus normal development and physiology - are
specified via proteins that control the organization and dynamic properties of
the actin cytoskeleton. Using the Drosophila model, we have recently identified
an unusual actin regulatory enzyme, Mical, which is directly activated by F-actin
to selectively post-translationally oxidize and destabilize filaments -
regulating numerous cellular behaviors. Mical proteins are also present in
mammals, but their actin regulatory properties, including comparisons among
different family members, remain poorly defined. We now find that each human
MICAL family member, MICAL-1, MICAL-2, and MICAL-3, directly induces F-actin
dismantling and controls F-actin-mediated cellular remodeling. Specifically, each
human MICAL selectively associates with F-actin, which directly induces MICALs
catalytic activity. We also find that each human MICAL uses an NADPH-dependent
Redox activity to post-translationally oxidize actin's methionine (M) M44/M47
residues, directly dismantling filaments and limiting new polymerization. Genetic
experiments also demonstrate that each human MICAL drives F-actin disassembly in
vivo, reshaping cells and their membranous extensions. Our results go on to
reveal that MsrB/SelR reductase enzymes counteract each MICAL's effect on F-actin
in vitro and in vivo. Collectively, our results therefore define the MICALs as an
important phylogenetically-conserved family of catalytically-acting F-actin
disassembly factors.
PMID- 29343824
TI - Human Papillomavirus Prophylactic Vaccination improves reproductive outcome in
infertile patients with HPV semen infection: a retrospective study.
AB - In this study we aimed to evaluate the effect on reproductive outcome of HPV
vaccination in male subjects of infertile couples with HPV semen infection. In
this single-center study, we retrospectively enrolled 151 infertile couples with
detection of HPV in semen, attending our Hospital Unit of Andrology between
January 2013 and June 2015, counseled to receive adjuvant HPV vaccination.
Seventy-nine accepted vaccination (vaccine group) whilst 72 did not (control
group). Our protocol of follow-up, aimed to evaluate HPV viral clearance,
consisted in semen analysis, INNO-LiPA and FISH for HPV in semen cells after 6
and 12 months from basal evaluation. Spontaneous pregnancies, miscarriages and
live births were recorded. Progressive sperm motility and anti-sperm antibodies
were improved in the vaccine group at both time points (p < 0,05 vs control arm).
Forty-one pregnancies, 11 in the control group and 30 in the vaccine group, were
recorded (respectively 15% and 38,9%, p < 0,05) and resulted into 4 deliveries
and 7 miscarriages (control group) and 29 deliveries and one miscarriage (vaccine
group, p < 0,05 vs control group). HPV detection on sperms was predictive of
negative pregnancy outcome. Adjuvant vaccination associated with enhanced HPV
healing in semen cells and increased rate of natural pregnancies and live births.
PMID- 29343825
TI - A Survey of Validation Strategies for CRISPR-Cas9 Editing.
AB - The T7 endonuclease 1 (T7E1) mismatch detection assay is a widely used method for
evaluating the activity of site-specific nucleases, such as the clustered
regularly interspaced short palindromic repeats (CRISPR)-Cas9 system. To
determine the accuracy and sensitivity of this assay, we compared the editing
estimates derived by the T7E1 assay with that of targeted next-generation
sequencing (NGS) in pools of edited mammalian cells. Here, we report that
estimates of nuclease activity determined by T7E1 most often do not accurately
reflect the activity observed in edited cells. Editing efficiencies of CRISPR
Cas9 complexes with similar activity by T7E1 can prove dramatically different by
NGS. Additionally, we compared editing efficiencies predicted by the Tracking of
Indels by Decomposition (TIDE) assay and the Indel Detection by Amplicon Analysis
(IDAA) assay to that observed by targeted NGS for both cellular pools and single
cell derived clones. We show that targeted NGS, TIDE, and IDAA assays predict
similar editing efficiencies for pools of cells but that TIDE and IDAA can
miscall alleles in edited clones.
PMID- 29343826
TI - Mammalian sterile 20 kinase 1 and 2 are important regulators of hematopoietic
stem cells in stress condition.
AB - The mammalian Hippo signaling pathway has been implicated in the self-renewal and
differentiation of stem and progenitor cells. MST1 and MST2 (MST1/2) are core
serine-threonine kinases in the Hippo signaling pathway, one of which, MST1, has
been extensively investigated for its role in T cell and myeloid cell function.
These studies have identified MST1 as a promising therapeutic target in
immunological disease. However, the roles of MST1/2 in hematopoietic stem cell
(HSC) function in vivo are not fully understood. Here, we report that mice with a
conditional deletion of Mst1/2 exhibit impaired hematopoietic stem and progenitor
cell (HSPC) function under stress condition. Furthermore, Mst1/2 deletion
markedly altered mature cell output. Therefore, MST1/2 are indispensable for
maintenance as well as function of stem and progenitor cells under steady state
conditions and with transplantation stress.
PMID- 29343828
TI - Widespread persistent changes to temperature extremes occurred earlier than
predicted.
AB - A critical question for climate mitigation and adaptation is to understand when
and where the signal of changes to climate extremes have persistently emerged or
will emerge from the background noise of climate variability. Here we show
observational evidence that such persistent changes to temperature extremes have
already occurred over large parts of the Earth. We further show that climate
models forced with natural and anthropogenic historical forcings underestimate
these changes. In particular, persistent changes have emerged in observations
earlier and over a larger spatial extent than predicted by models. The delayed
emergence in the models is linked to a combination of simulated change ('signal')
that is weaker than observed, and simulated variability ('noise') that is greater
than observed. Over regions where persistent changes had not occurred by the year
2000, we find that most of the observed signal-to-noise ratios lie within the 16
84% range of those simulated. Examination of simulations with and without
anthropogenic forcings provides evidence that the observed changes are more
likely to be anthropogenic than nature in origin. Our findings suggest that
further changes to temperature extremes over parts of the Earth are likely to
occur earlier than projected by the current climate models.
PMID- 29343827
TI - Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells.
AB - With a diverse network of substrates, NUDIX hydrolases have emerged as a key
family of nucleotide-metabolizing enzymes. NUDT5 (also called NUDIX5) has been
implicated in ADP-ribose and 8-oxo-guanine metabolism and was recently identified
as a rheostat of hormone-dependent gene regulation and proliferation in breast
cancer cells. Here, we further elucidate the physiological relevance of known
NUDT5 substrates and underscore the biological requirement for NUDT5 in gene
regulation and proliferation of breast cancer cells. We confirm the involvement
of NUDT5 in ADP-ribose metabolism and dissociate a relationship to oxidized
nucleotide sanitation. Furthermore, we identify potent NUDT5 inhibitors, which
are optimized to promote maximal NUDT5 cellular target engagement by CETSA. Lead
compound, TH5427, blocks progestin-dependent, PAR-derived nuclear ATP synthesis
and subsequent chromatin remodeling, gene regulation and proliferation in breast
cancer cells. We herein present TH5427 as a promising, targeted inhibitor that
can be used to further study NUDT5 activity and ADP-ribose metabolism.
PMID- 29343830
TI - Biological rejuvenation of iron oxides in bioturbated marine sediments.
AB - The biogeochemical cycle of iron is intricately linked to numerous element
cycles. Although biological processes that catalyze the reductive side of the
iron cycle are established, little is known about microbial oxidative processes
on iron cycling in sedimentary environments-resulting in the formation of iron
oxides. Here we show that a potential source of sedimentary iron oxides
originates from the metabolic activity of iron-oxidizing bacteria from the class
Zetaproteobacteria, presumably enhanced by burrowing animals in coastal
sediments. Zetaproteobacteria were estimated to be a global total of 1026 cells
in coastal, bioturbated sediments, and predicted to annually produce 8 * 1015 g
of Fe in sedimentary iron oxides-55 times larger than the annual flux of iron
oxides deposited by rivers. These data suggest that iron-oxidizing
Zetaproteobacteria are keystone organisms in marine sedimentary environments
despite their low numerical abundance-yet exert a disproportionate impact via the
rejuvenation of iron oxides.
PMID- 29343829
TI - Targeted inhibitors of P-glycoprotein increase chemotherapeutic-induced mortality
of multidrug resistant tumor cells.
AB - Overexpression of ATP-binding cassette (ABC) transporters is often linked to
multidrug resistance (MDR) in cancer chemotherapies. P-glycoprotein (P-gp) is one
of the best studied drug transporters associated with MDR. There are currently no
approved drugs available for clinical use in cancer chemotherapies to reverse MDR
by inhibiting P-glycoprotein. Using computational studies, we previously
identified several compounds that inhibit P-gp by targeting its nucleotide
binding domain and avoiding its drug binding domains. Several of these compounds
showed successful MDR reversal when tested on a drug resistant prostate cancer
cell line. Using conventional two-dimensional cell culture of MDR ovarian and
prostate cancer cells and three dimensional prostate cancer microtumor spheroids,
we demonstrated here that co-administration with chemotherapeutics significantly
decreased cell viability and survival as well as cell motility. The P-gp
inhibitors were not observed to be toxic on their own. The inhibitors increased
cellular retention of chemotherapeutics and reporter compounds known to be
transport substrates of P-gp. We also showed that these compounds are not
transport substrates of P-gp and that two of the three inhibit P-gp, but not the
closely related ABC transporter, ABCG2/BCRP. The results presented suggest that
these P-gp inhibitors may be promising leads for future drug development.
PMID- 29343831
TI - Novel hydrogenases from deep-sea hydrothermal vent metagenomes identified by a
recently developed activity-based screen.
AB - Hydrogen is one of the most common elements on Earth. The enzymes converting
molecular hydrogen into protons and electrons are the hydrogenases. Hydrogenases
are ubiquitously distributed in all three domains of life where they play a
central role in cell metabolism. So far, the recovery of hydrogenases has been
restricted to culture-dependent and sequence-based approaches. We have recently
developed the only activity-based screen for seeking H2-uptake enzymes from
metagenomes without having to rely on enrichment and isolation of hydrogen
oxidizing microorganisms or prior metagenomic sequencing. When screening 14,400
fosmid clones from three hydrothermal vent metagenomes using this solely activity
based approach, four clones with H2-uptake activity were identified with specific
activities of up to 258 +/- 19 nmol H2/min/mg protein of partially purified
membrane fractions. The respective metagenomic fragments exhibited mostly very
low or no similarities to sequences in the public databases. A search with hidden
Markov models for different hydrogenase groups showed no hits for three of the
four metagenomic inserts, indicating that they do not encode for classical
hydrogenases. Our activity-based screen serves as a powerful tool for the
discovery of (novel) hydrogenases which would not have been identified by the
currently available techniques. This screen can be ideally combined with culture-
and sequence-based approaches to investigate the tremendous hydrogen-converting
potential in the environment.
PMID- 29343832
TI - Infection dynamics of insecticide-degrading symbionts from soil to insects in
response to insecticide spraying.
AB - Insecticide resistance is a serious concern in modern agriculture, and an
understanding of the underlying evolutionary processes is pivotal to prevent the
problem. The bean bug Riptortus pedestris, a notorious pest of leguminous crops,
acquires a specific Burkholderia symbiont from the environment every generation,
and harbors the symbiont in the midgut crypts. The symbiont's natural role is to
promote insect development but the insect host can also obtain resistance against
the insecticide fenitrothion (MEP) by acquiring MEP-degrading Burkholderia from
the environment. To understand the developing process of the symbiont-mediated
MEP resistance in response to the application of the insecticide, we investigated
here in parallel the soil bacterial dynamics and the infected gut symbionts under
different MEP-spraying conditions by culture-dependent and culture-independent
analyses, in conjunction with stinkbug rearing experiments. We demonstrate that
MEP application did not affect the total bacterial soil population but
significantly decreased its diversity while it dramatically increased the
proportion of MEP-degrading bacteria, mostly Burkholderia. Moreover, we found
that the infection of stinkbug hosts with MEP-degrading Burkholderia is highly
specific and efficient, and is established after only a few times of insecticide
spraying at least in a field soil with spraying history, suggesting that
insecticide resistance could evolve in a pest bug population more quickly than
was thought before.
PMID- 29343834
TI - Newly discovered Late Triassic Baqing eclogite in central Tibet indicates an
anticlockwise West-East Qiangtang collision.
AB - The Triassic eclogite-bearing central Qiangtang metamorphic belt (CQMB) in the
northern Tibetan Plateau has been debated whether it is a metamorphic core
complex underthrust from the Jinsha Paleo-Tethys or an in-situ Shuanghu suture.
The CQMB is thus a key issue to elucidate the crustal architecture of the
northern Tibetan Plateau, the tectonics of the eastern Tethys, and the
petrogenesis of Cenozoic high-K magmatism. We here report the newly discovered
Baqing eclogite along the eastern extension of the CQMB near the Baqing town,
central Tibet. These eclogites are characterized by the garnet + omphacite +
rutile + phengite + quartz assemblages. Primary eclogite-facies metamorphic
pressure-temperature estimates yield consistent minimum pressure of 25 +/- 1 kbar
at 730 +/- 60 degrees C. U-Pb dating on zircons that contain inclusions (garnet
+ omphacite + rutile + phengite) gave eclogite-facies metamorphic ages of 223 Ma.
The geochemical continental crustal signature and the presence of Paleozoic cores
in the zircons indicate that the Baqing eclogite formed by continental subduction
and marks an eastward-younging anticlockwise West-East Qiangtang collision along
the Shuanghu suture from the Middle to Late Triassic.
PMID- 29343833
TI - Dopamine D3 receptor antagonist reveals a cryptic pocket in aminergic GPCRs.
AB - The recent increase in the number of X-ray crystal structures of G-protein
coupled receptors (GPCRs) has been enabling for structure-based drug design
(SBDD) efforts. These structures have revealed that GPCRs are highly dynamic
macromolecules whose function is dependent on their intrinsic flexibility.
Unfortunately, the use of static structures to understand ligand binding can
potentially be misleading, especially in systems with an inherently high degree
of conformational flexibility. Here, we show that docking a set of dopamine D3
receptor compounds into the existing eticlopride-bound dopamine D3 receptor (D3R)
X-ray crystal structure resulted in poses that were not consistent with results
obtained from site-directed mutagenesis experiments. We overcame the limitations
of static docking by using large-scale high-throughput molecular dynamics (MD)
simulations and Markov state models (MSMs) to determine an alternative pose
consistent with the mutation data. The new pose maintains critical interactions
observed in the D3R/eticlopride X-ray crystal structure and suggests that a
cryptic pocket forms due to the shift of a highly conserved residue, F6.52. Our
study highlights the importance of GPCR dynamics to understand ligand binding and
provides new opportunities for drug discovery.
PMID- 29343835
TI - A non-zircon Hf isotope record in Archean black shales from the Pilbara craton
confirms changing crustal dynamics ca. 3 Ga ago.
AB - Plate tectonics and associated subduction are unique to the Earth. Studies of
Archean rocks show significant changes in composition and structural style around
3.0 to 2.5 Ga that are related to changing tectonic regime, possibly associated
with the onset of subduction. Whole rock Hf isotope systematics of black shales
from the Australian Pilbara craton, selected to exclude detrital zircon
components, are employed to evaluate the evolution of the Archean crust. This
approach avoids limitations of Hf-in-zircon analyses, which only provide input
from rocks of sufficient Zr-concentration, and therefore usually represent
domains that already underwent a degree of differentiation. In this study, we
demonstrate the applicability of this method through analysis of shales that
range in age from 3.5 to 2.8 Ga, and serve as representatives of their crustal
sources through time. Their Hf isotopic compositions show a trend from strongly
positive epsilonHfinitial values for the oldest samples, to strongly negative
values for the younger samples, indicating a shift from juvenile to
differentiated material. These results confirm a significant change in the
character of the source region of the black shales by 3 Ga, consistent with
models invoking a change in global dynamics from crustal growth towards crustal
reworking around this time.
PMID- 29343836
TI - BPX-501 T cells interfere with minimal residual disease evaluation of B-cell
acute lymphoblastic leukemia.
PMID- 29343838
TI - Estimating the impact of body mass index on bladder cancer risk: Stratification
by smoking status.
AB - We estimated the impact of obesity on bladder cancer with stratification by
smoking status using nationally representative data on the Korean population from
the National Health Insurance System (NHIS). Of the 45,850,458 people who
underwent at last one health examination from 2009 to 2012, 23,378,895 without
bladder cancer were followed from the January 2009 to the December 2015. First,
the HR for bladder cancer was lowest in people with a BMI < 18.5 (HR = 0.92) and
highest for those with BMI >= 30 (HR = 1.17) in multiple Cox regression analyses.
The positive association between bladder cancer and BMI showed an increasing
trend beyond the reference BMI. Second, an analysis of HR for bladder cancer
stratified by obesity across smoking status strata showed a significant trend of
increasing HR for bladder cancer across obesity and smoking status in
multivariate-adjusted models. Conclusively, this population-based study showed
that increasing BMI was a risk factor for bladder cancer independent of
confounding variables. When stratified by smoking status, there was still a
positive association between bladder cancer and BMI (P for trend < 0.01).
PMID- 29343839
TI - Musical auditory stimulus acutely influences heart rate dynamic responses to
medication in subjects with well-controlled hypertension.
AB - Music can improve the efficiency of medical treatment when correctly associated
with drug action, reducing risk factors involving deteriorating cardiac function.
We evaluated the effect of musical auditory stimulus associated with anti
hypertensive medication on heart rate (HR) autonomic control in hypertensive
subjects. We evaluated 37 well-controlled hypertensive patients designated for
anti-hypertensive medication. Heart rate variability (HRV) was calculated from
the HR monitor recordings of two different, randomly sorted protocols (control
and music) on two separate days. Patients were examined in a resting condition 10
minutes before medication and 20 minutes, 40 minutes and 60 minutes after oral
medication. Music was played throughout the 60 minutes after medication with the
same intensity for all subjects in the music protocol. We noted analogous
response of systolic and diastolic arterial pressure in both protocols. HR
decreased 60 minutes after medication in the music protocol while it remained
unchanged in the control protocol. The effects of anti-hypertensive medication on
SDNN (Standard deviation of all normal RR intervals), LF (low frequency, nu), HF
(high frequency, nu) and alpha-1 scale were more intense in the music protocol.
In conclusion, musical auditory stimulus increased HR autonomic responses to anti
hypertensive medication in well-controlled hypertensive subjects.
PMID- 29343840
TI - Vision Status in Older Adults: The Brazilian Amazon Region Eye Survey.
AB - Older adults living in remote areas with limited access to health services are at
higher risk to develop visual impairment and blindness. We conducted a population
based survey to determine the vision status in subjects 45 years of age and older
from urban and rural areas of Parintins city, Brazilian Amazon Region.
Participants underwent ophthalmic examination, including uncorrected (UCVA),
presenting (PVA) and best-corrected visual acuity (BCVA). Vision status was
described as lines of visual acuity (VA) impairment and lines of VA improvement
from UCVA to BCVA and from PVA to BCVA in the better-seeing eye. A total of 2384
subjects were enumerated, 2041 (85.6%) were examined, with reliable VA
measurements obtained from 2025 participants. Vision status in lines of VA
impairment was (mean +/- standard deviation): 3.44 +/- 3.53 for UCVA, 2.85 +/-
3.52 for PVA and 1.50 +/- 3.51 for BCVA. Female gender, older age and lower
education were associated with >=6 lines of UCVA impairment. Lines of improvement
>=3 was found in 626 (30.9%) participants and associated with female gender and
rural residency. In conclusion, a third of participants could have at least three
lines of VA improvement with proper refraction. Strategies to improve access to
eye care and affordable glasses are needed.
PMID- 29343837
TI - Neurocognitive dysfunction in hematopoietic cell transplant recipients: expert
review from the late effects and Quality of Life Working Committee of the CIBMTR
and complications and Quality of Life Working Party of the EBMT.
AB - Hematopoietic cell transplantation (HCT) is a potentially curative treatment for
children and adults with malignant and non-malignant diseases. Despite increasing
survival rates, long-term morbidity following HCT is substantial. Neurocognitive
dysfunction is a serious cause of morbidity, yet little is known about
neurocognitive dysfunction following HCT. To address this gap, collaborative
efforts of the Center for International Blood and Marrow Transplant Research and
the European Society for Blood and Marrow Transplantation undertook an expert
review of neurocognitive dysfunction following HCT. In this review, we define
what constitutes neurocognitive dysfunction, characterize its risk factors and
sequelae, describe tools and methods to assess neurocognitive function in HCT
recipients, and discuss possible interventions for HCT patients with this
condition. This review aims to help clinicians understand the scope of this
health-related problem, highlight its impact on well-being of survivors, and to
help determine factors that may improve identification of patients at risk for
declines in cognitive functioning after HCT. In particular, we review strategies
for preventing and treating neurocognitive dysfunction in HCT patients. Lastly,
we highlight the need for well-designed studies to develop and test interventions
aimed at preventing and improving neurocognitive dysfunction and its sequelae
following HCT.
PMID- 29343841
TI - Microdosimetric Modeling of Biological Effectiveness for Boron Neutron Capture
Therapy Considering Intra- and Intercellular Heterogeneity in 10B Distribution.
AB - We here propose a new model for estimating the biological effectiveness for boron
neutron capture therapy (BNCT) considering intra- and intercellular heterogeneity
in 10B distribution. The new model was developed from our previously established
stochastic microdosimetric kinetic model that determines the surviving fraction
of cells irradiated with any radiations. In the model, the probability density of
the absorbed doses in microscopic scales is the fundamental physical index for
characterizing the radiation fields. A new computational method was established
to determine the probability density for application to BNCT using the Particle
and Heavy Ion Transport code System PHITS. The parameters used in the model were
determined from the measured surviving fraction of tumor cells administrated with
two kinds of 10B compounds. The model quantitatively highlighted the
indispensable need to consider the synergetic effect and the dose dependence of
the biological effectiveness in the estimate of the therapeutic effect of BNCT.
The model can predict the biological effectiveness of newly developed 10B
compounds based on their intra- and intercellular distributions, and thus, it can
play important roles not only in treatment planning but also in drug discovery
research for future BNCT.
PMID- 29343843
TI - Cathelicidin-OA1, a novel antioxidant peptide identified from an amphibian,
accelerates skin wound healing.
AB - Cathelicidins play pivotal roles in host defense. The discovery of novel
cathelicidins is important research; however, despite the identification of many
cathelicidins in vertebrates, few have been reported in amphibians. Here we
identified a novel cathelicidin (named cathelicidin-OA1) from the skin of an
amphibian species, Odorrana andersonii. Produced by posttranslational processing
of a 198-residue prepropeptide, cathelicidin-OA1 presented an amino acid sequence
of 'IGRDPTWSHLAASCLKCIFDDLPKTHN' and a molecular mass of 3038.5 Da. Functional
analysis showed that, unlike other cathelicidins, cathelicidin-OA1 demonstrated
no direct microbe-killing, acute toxicity and hemolytic activity, but did exhibit
antioxidant activity. Importantly, cathelicidin-OA1 accelerated wound healing
against human keratinocytes (HaCaT) and skin fibroblasts (HSF) in both time- and
dose-dependent manners. Notably, cathelicidin-OA1 also showed wound-healing
promotion in a mouse model with full-thickness skin wounds, accelerating re
epithelialization and granulation tissue formation by enhancing the recruitment
of macrophages to the wound site, inducing HaCaT cell proliferation and HSF cell
migration. This is the first cathelicidin identified from an amphibian that shows
potent wound-healing activity. These results will help in the development of new
types of wound-healing agents and in our understanding of the biological
functions of cathelicidins.
PMID- 29343844
TI - Determinants of population responses to environmental fluctuations.
AB - Environmental fluctuations, such as changing conditions and variable nutrient
availability, are an unavoidable component of the dynamics of virtually all
populations. They affect populations in ways that are often difficult to predict
and sometimes lead to paradoxical outcomes. Here, we present a general analytical
approach to examine how populations respond to fluctuations. We show that there
exist general explicit conditions that determine to what extent fluctuations
propagate to the variability of the responses and how they change the behavior of
the system, including whether they promote proliferation or death and whether
they facilitate coexistence or exclusion of competing species. These conditions
depend on linear and nonlinear terms of the growth rate and on the characteristic
times of the fluctuations. We validated our general approach through
computational experiments for both stochastic and chaotic fluctuations and for
multiple types of systems. From an applied point of view, our results provide an
avenue for the precise control of the population behavior through fluctuations in
addition to just through average properties.
PMID- 29343842
TI - Leptin resistance was involved in susceptibility to overweight in the striped
hamster re-fed with high fat diet.
AB - Food restriction (FR) is the most commonly used intervention to prevent the
overweight. However, the lost weight is usually followed by "compensatory growth"
when FR ends, resulting in overweight. The present study was aimed to examining
the behavior patterns and hormones mechanisms underpinning the over-weight.
Energy budget and body fat content, and several endocrine markers related to
leptin signals were examined in the striped hamsters under 20% FR refed by either
low-fat diet (LF group) or high-fat diet (HF group). Body mass and fat content
significantly regained when FR ended, and the hamsters in HF group showed 49.1%
more body fat than in LF group (P < 0.01). Digestive energy intake was higher by
20.1% in HF than LF group, while metabolic thermogenesis and behavior patterns
did not differed between the two groups. Gene expression of leptin receptor and
anorexigenic peptides of pro-opiomelanocortin and cocaine- and amphetamine
regulated transcript in hypothalamus were significantly up-regulated in LF group,
but down-regulated in HF group. It suggests that effective leptin signals to the
brain were involved in attenuation of hyperphagia in hamsters refed with LF.
However, "leptin resistance" probably occurred in hamsters refed with HF, which
impaired the control of hyperphagia, resulting in development of over-weight.
PMID- 29343845
TI - Metal-free magnetism, spin-dependent Seebeck effect, and spin-Seebeck diode
effect in armchair graphene nanoribbons.
AB - Metal-free magnetism and spin caloritronics are at the forefront of condensed
matter physics. Here, the electronic structures and thermal spin-dependent
transport properties of armchair graphene nanoribbons (N-AGNRs), where N is the
ribbon width (N = 5-23), are systematically studied. The results show that the
indirect band gaps exhibit not only oscillatory behavior but also periodic
characteristics with E 3p > E3p+1 > E3p+2 (E 3p , E3p+1 and E3p+2 are the band
gaps energy) for a certain integer p, with increasing AGNR width. The magnetic
ground states are ferromagnetic (FM) with a Curie temperatures (T C ) above room
temperature. Furthermore, the spin-up and spin-down currents with opposite
directions, generated by a temperature gradient, are almost symmetrical,
indicating the appearance of the perfect spin-dependent Seebeck effect (SDSE).
Moreover, thermally driven spin currents through the nanodevices induced the spin
Seebeck diode (SSD) effect. Our calculation results indicated that AGNRs can be
applied in thermal spin nanodevices.
PMID- 29343846
TI - Author Correction: CODA: Integrating multi-level context-oriented directed
associations for analysis of drug effects.
AB - A correction to this article has been published and is linked from the HTML
version of this paper. The error has been fixed in the paper.
PMID- 29343847
TI - Neural substrates of purely endogenous, self-regulatory control of attention.
AB - Stimulus-driven orienting of attention toward a novel, salient stimulus is a
highly adaptive behavior. In an opposing vein, it is also crucial to endogenously
redirect attention to other stimuli of behavioral significance if the attended
stimulus was evaluated to be unimportant. This stimulus-driven orienting and
subsequent reorienting of attention are known to be mediated by similar neural
substrates. However, this might be because reorienting was triggered by a sensory
transition exogenously capturing attention, such as an abrupt onset of a new
stimulus. Here, we used fMRI to measure the human brain's activity when attention
captured by a salient distractor is endogenously reoriented toward the concurrent
main task, without any exogenous shifting of attention. As results, the transient
activity of the anterior insula (AI) signaled such endogenous reorienting,
predicting behavioral performance. This finding points to the central role of the
AI in purely endogenous, self-regulatory control of attention.
PMID- 29343848
TI - A novel protein encoded by the circular form of the SHPRH gene suppresses glioma
tumorigenesis.
AB - Circular RNAs (circRNAs) are recognized as functional non-coding transcripts in
eukaryotic cells. Recent evidence has indicated that even though circRNAs are
generally expressed at low levels, they may be involved in many physiological or
pathological processes, such as gene regulation, tissue development and
carcinogenesis. Although the 'microRNA sponge' function is well characterized,
most circRNAs do not contain perfect trapping sites for microRNAs, which suggests
the possibility that circRNAs have functions that have not yet been defined. In
this study, we show that a circRNA containing an open reading frame (ORF) driven
by the internal ribosome entry site (IRES) can translate a functional protein.
The circular form of the SNF2 histone linker PHD RING helicase (SHPRH) gene
encodes a novel protein that we termed SHPRH-146aa. Circular SHPRH (circ-SHPRH)
uses overlapping genetic codes to generate a 'UGA' stop codon, which results in
the translation of the 17 kDa SHPRH-146aa. Both circ-SHPRH and SHPRH-146aa are
abundantly expressed in normal human brains and are down-regulated in
glioblastoma. The overexpression of SHPRH-146aa in U251 and U373 glioblastoma
cells reduces their malignant behavior and tumorigenicity in vitro and in vivo.
Mechanistically, SHPRH-146aa protects full-length SHPRH from degradation by the
ubiquitin proteasome. Stabilized SHPRH sequentially ubiquitinates proliferating
cell nuclear antigen (PCNA) as an E3 ligase, leading to inhibited cell
proliferation and tumorigenicity. Our findings provide a novel perspective
regarding circRNA function in physiological and pathological processes.
Specifically, SHPRH-146aa generated from overlapping genetic codes of circ-SHPRH
is a tumor suppressor in human glioblastoma.
PMID- 29343849
TI - Mutant p53 gain of function underlies high expression levels of colorectal cancer
stem cells markers.
AB - Emerging notion in carcinogenesis ascribes tumor initiation and aggressiveness to
cancer stem cells (CSCs). Specifically, colorectal cancer (CRC) development was
shown to be compatible with CSCs hypothesis. Mutations in p53 are highly frequent
in CRC, and are known to facilitate tumor development and aggressiveness. Yet,
the link between mutant p53 and colorectal CSCs is not well-established. In the
present study, we set to examine whether oncogenic mutant p53 proteins may
augment colorectal CSCs phenotype. By genetic manipulation of mutant p53 in
several cellular systems, we demonstrated that mutant p53 enhances colorectal
tumorigenesis. Moreover, mutant p53-expressing cell lines harbor larger sub
populations of cells highly expressing the known colorectal CSCs markers: CD44,
Lgr5, and ALDH. This elevated expression is mediated by mutant p53 binding to
CD44, Lgr5, and ALDH1A1 promoter sequences. Furthermore, ALDH1 was found to be
involved in mutant p53-dependent chemotherapy resistance. Finally, analysis of
ALDH1 and CD44 in human CRC biopsies indicated a positive correlation between
their expression and the presence of oncogenic p53 missense mutations. These
findings suggest novel insights pertaining the mechanism by which mutant p53
enhances CRC development, which involves the expansion of CSCs sub-populations
within CRC tumors, and underscore the importance of targeting these sub
populations for CRC therapy.
PMID- 29343850
TI - MiRNA-646-mediated reciprocal repression between HIF-1alpha and MIIP contributes
to tumorigenesis of pancreatic cancer.
AB - Migration and invasion inhibitory protein (MIIP) is recently identified as an
inhibitor in tumor development. However, the regulatory mechanism and biological
contributions of MIIP in pancreatic cancer (PC) have been not elucidated. In this
study, we demonstrated a negative feedback of MIIP and hypoxia-induced factor
1alpha (HIF-1alpha), which was mediated by a hypoxia-induced microRNA. Compared
with paracarcinoma tissues, MIIP was downregulated in PC tissues. Overexpression
of MIIP significantly impeded the proliferation and invasion of PC cells both in
vitro and in mouse xenograft models. We further verified MIIP was downregulated
under hypoxia in a HIF-1alpha-mediated manner. Interestingly, although MIIP
promoter containing two putative hypoxia response elements (HREs), the chromatin
immunoprecipitation (ChIP) and luciferase reporter assays did not support an
active interaction between HIF-1alpha and MIIP promoter. Meanwhile, microRNA
array revealed a hypoxia-induced microRNA, miR-646, impaired stability of MIIP
mRNA and consequently inhibited its expression by targeting the coding sequence
(CDS). Coincidently, knockdown of miR-646 significantly repressed proliferation
and invasion ability of PC cells both in vitro and in vivo by upregulating MIIP
expression. Besides, ChIP and luciferase reporter assays further validated that
HIF-1alpha activated transcription of miR-646 in hypoxia condition. Therefore,
these results suggested HIF-1alpha indirectly regulated MIIP expression in post
transcriptional level through upregulating miR-646 transcription. Conversely, our
results further revealed that MIIP suppressed deacetylase ability of histone
deacetylase 6 (HDAC6) to promote the acetylation and degradation of HIF-1alpha,
by which impairing HIF-1alpha accumulation. What is more, a specific relationship
between downregulated MIIP and upregulated miR-646 expression was validated in PC
samples. Moreover, the dysregulated miR-646 and MIIP expression was correlated
with advanced tumor stage, lymphatic invasion, metastasis and shorter overall
survival in PC patients. Together, our results highlight that the reciprocal loop
of HIF-1alpha/miR-646/MIIP might be implemented as an applicable target for
pancreatic cancer therapy.
PMID- 29343851
TI - NDRG2 facilitates colorectal cancer differentiation through the regulation of
Skp2-p21/p27 axis.
AB - Poorly differentiated colorectal cancers (CRCs) are more aggressive and lack
targeted therapies. We and others previously reported the predominant role of
tumor-suppressor NDRG2 in promoting CRC differentiation, but the underlying
mechanism is largely unknown. Herein, we demonstrate that NDRG2 induction of CRC
cell differentiation is dependent on the repression of E3 ligase Skp2 activity.
In patients and Ndrg2 knockout mice, NDRG2 and Skp2 are negatively correlated and
associated with cell differentiation stage. Further, NDRG2 suppression of Skp2
contributes to the inductions and stabilizations of p21 and p27, which are Skp2
target proteins for degradation. The reduction of either p21 or p27 levels by
shRNA can decrease NDRG2-induced AKP activity and resume cell growth inhibition,
thus both p21 and p27 are required for NDRG2 effect on the promotion of cell
differentiation in CRCs. The mechanistic study shows that NDRG2 suppresses beta
catenin nuclear translocation and decreases the occupancy of beta-catenin/TCF
complex on Skp2 promoter, potentially through dephosphorylating GSK-3beta. By
subjecting a series of NDRG2 deletion mutants to Skp2 expression, the loss of NH2
terminal domain can completely abolish NDRG2-dependent differentiation induction.
Supporting the biological significance of the reciprocal relationship between
NDRG2 and Skp2, an NDRG2low/Skp2high gene expression signature correlates with
poor CRC patient outcome and could be considered as a diagnostic marker of CRCs.
PMID- 29343852
TI - A new class of magnetically actuated pumps and valves for microfluidic
applications.
AB - We propose a new class of magnetically actuated pumps and valves that could be
incorporated into microfluidic chips with no further external connections. The
idea is to repurpose ferromagnetic low Reynolds number swimmers as devices
capable of generating fluid flow, by restricting the swimmers' translational
degrees of freedom. We experimentally investigate the flow structure generated by
a pinned swimmer in different scenarios, such as unrestricted flow around it as
well as flow generated in straight, cross-shaped, Y-shaped and circular channels.
This demonstrates the feasibility of incorporating the device into a channel and
its capability of acting as a pump, valve and flow splitter. Different regimes
could be selected by tuning the frequency and amplitude of the external magnetic
field driving the swimmer, or by changing the channel orientation with respect to
the field. This versatility endows the device with varied functionality which,
together with the robust remote control and reproducibility, makes it a promising
candidate for several applications.
PMID- 29343854
TI - Towards healthier supermarkets: a national study of in-store food availability,
prominence and promotions in New Zealand.
AB - BACKGROUND/OBJECTIVES: The retail environment is a key setting for potential
public health interventions. This study assessed the healthiness of New Zealand
supermarket food environments. SUBJECT/METHODS: A sample of 204 (about 50% of
national total) supermarkets across three chains was selected in 2016, half in
the most deprived socioeconomic areas. Healthiness indicators related to food
availability (ratio of cumulative linear shelf length for healthy versus
unhealthy foods), prominence (proportion of 'junk food free' check-outs and end
of-aisle endcaps), and promotion (proportion of 'junk food free' promotions in
flyers and in-store) were measured. RESULTS: About 26.5% of supermarkets had at
least 20% of check-outs junk-food-free and 17.2% had at least 60% of endcaps junk
food free. On average 2/3 of food promotions in-store and 3/4 of food promotions
in flyers were junk food free. For every 1 m of shelf length for unhealthy foods,
there was 42 cm of shelf length for healthy foods on average, with large
variations between and within stores. In high and low prominence store areas
there was on average 1 m of unhealthy foods for every 2 cm of healthy foods and 1
m of unhealthy foods for every 4 m of healthy foods, respectively. The shelf
length ratio was significantly lower in the most compared to the least/medium
deprived socioeconomic areas (p = 0.003). CONCLUSIONS: The large variations in
healthiness indicators within and across chains present a great opportunity for
retailers to improve the healthiness of supermarkets towards best practice.
PMID- 29343853
TI - Differential tissue specific, temporal and spatial expression patterns of the
Aggrecan gene is modulated by independent enhancer elements.
AB - The transcriptional mechanism through which chondrocytes control the spatial and
temporal composition of the cartilage tissue has remained largely elusive. The
central aim of this study was to identify whether transcriptional enhancers
played a role in the organisation of the chondrocytes in cartilaginous tissue. We
focused on the Aggrecan gene (Acan) as it is essential for the normal structure
and function of cartilage and it is expressed developmentally in different stages
of chondrocyte maturation. Using transgenic reporter studies in mice we
identified four elements, two of which showed individual chondrocyte
developmental stage specificity. In particular, one enhancer (-80) distinguishes
itself from the others by being predominantly active in adult cartilage.
Furthermore, the -62 element uniquely drove reporter activity in early
chondrocytes. The remaining chondrocyte specific enhancers, +28 and -30, showed
no preference to chondrocyte type. The transcription factor SOX9 interacted with
all the enhancers in vitro and mutation of SOX9 binding sites in one of the
enhancers (-30) resulted in a loss of its chondrocyte specificity and ectopic
enhancer reporter activity. Thus, the Acan enhancers orchestrate the precise
spatiotemporal expression of this gene in cartilage types at different stages of
development and adulthood.
PMID- 29343855
TI - The ferroptosis inducer erastin irreversibly inhibits system xc- and synergizes
with cisplatin to increase cisplatin's cytotoxicity in cancer cells.
AB - System xc- was recently described as the most upstream node in a novel form of
regulated necrotic cell death, called ferroptosis. In this context, the small
molecule erastin was reported to target and inhibit system xc-, leading to
cysteine starvation, glutathione depletion and consequently ferroptotic cell
death. Although the inhibitory effect of erastin towards system xc- is well
documented, nothing is known about its mechanism of action. Therefore, we sought
to interrogate in more detail the underlying mechanism of erastin's pro
ferroptotic effects. When comparing with some well-known inhibitors of system xc
, erastin was the most efficient inhibitor acting at low micromolar
concentrations. Notably, only a very short exposure of cells with low erastin
concentrations was sufficient to cause a strong and persistent inhibition of
system xc-, causing glutathione depletion. These inhibitory effects towards
system xc- did not involve cysteine modifications of the transporter. More
importantly, short exposure of tumor cells with erastin strongly potentiated the
cytotoxic effects of cisplatin to efficiently eradicate tumor cells. Hence, our
data suggests that only a very short pre-treatment of erastin suffices to
synergize with cisplatin to efficiently induce cancer cell death, findings that
might guide us in the design of novel cancer treatment paradigms.
PMID- 29343856
TI - Deep-Ultraviolet AlGaN/AlN Core-Shell Multiple Quantum Wells on AlN Nanorods via
Lithography-Free Method.
AB - We report deep ultraviolet (UVC) emitting core-shell-type AlGaN/AlN multiple
quantum wells (MQWs) on the AlN nanorods which are prepared by
catalyst/lithography free process. The MQWs are grown on AlN nanorods on a
sapphire substrate by polarity-selective epitaxy and etching (PSEE) using high
temperature metal organic chemical vapor deposition. The AlN nanorods prepared
through PSEE have a low dislocation density because edge dislocations are bent
toward neighboring N-polar AlN domains. The core-shell-type MQWs grown on AlN
nanorods have three crystallographic orientations, and the final shape of the
grown structure is explained by a ball-and-stick model. The photoluminescence
(PL) intensity of MQWs grown on AlN nanorods is approximately 40 times higher
than that of MQWs simultaneously grown on a planar structure. This result can be
explained by increased internal quantum efficiency, large active volume, and
increase in light extraction efficiency based on the examination in this study.
Among those effects, the increase of active volume on AlN nanorods is considered
to be the main reason for the enhancement of the PL intensity.
PMID- 29343857
TI - Stimulation of Epicardial Sympathetic Nerves at Different Sites Induces Cardiac
Electrical Instability to Various Degrees.
AB - The cardiac sympathetic nerves distribute across cardiac tissues with uneven
density. Yet, to what extent this anatomical heterogeneity affects electrical
activity of the left ventricle is largely unknown. Dogs were randomized into non
stimulation control (NC), posterior basal-stimulation (PB), anterior superior
stimulation (AS), apical part-stimulation (AP) group. The epicardial sympathetic
nerves at different sites along their distribution were with electrical
stimulation (ES) for 4 hours except in the NC group. The myocardial effective
refractory period (ERP), ventricular fibrillation threshold (VFT) and density of
sympathetic nerves were recorded. Compared with ES at other places, the
stimulation at PB site significantly shortened ERP (left ventricular anterior and
posterior walls; PB group, 118 +/- 4 ms, 106 +/- 2 ms; Versus NC group, 155 +/-
3.5 ms, 160 +/- 3 ms; p < 0.01) and VFT (PB group, 11.5 +/- 1.5 V; Versus NC
group, 20.5 +/- 0.9 V; p < 0.01), and induced remarkable regeneration of the
cardiac sympathetic nerves, hence influencing electrical activity of the left
ventricle to the most extent. Our study demonstrates that the degree of induced
ventricular electrical instability is correlated tightly with the density of
sympathetic nerves around ES site, and PB site is a potential target for
modulating ventricular electrical activity to the maximal extent.
PMID- 29343859
TI - Rate after-effects fail to transfer cross-modally: Evidence for distributed
sensory timing mechanisms.
AB - Accurate time perception is critical for a number of human behaviours, such as
understanding speech and the appreciation of music. However, it remains
unresolved whether sensory time perception is mediated by a central timing
component regulating all senses, or by a set of distributed mechanisms, each
dedicated to a single sensory modality and operating in a largely independent
manner. To address this issue, we conducted a range of unimodal and cross-modal
rate adaptation experiments, in order to establish the degree of specificity of
classical after-effects of sensory adaptation. Adapting to a fast rate of sensory
stimulation typically makes a moderate rate appear slower (repulsive after
effect), and vice versa. A central timing hypothesis predicts general transfer of
adaptation effects across modalities, whilst distributed mechanisms predict a
high degree of sensory selectivity. Rate perception was quantified by a method of
temporal reproduction across all combinations of visual, auditory and tactile
senses. Robust repulsive after-effects were observed in all unimodal rate
conditions, but were not observed for any cross-modal pairings. Our results show
that sensory timing abilities are adaptable but, crucially, that this change is
modality-specific - an outcome that is consistent with a distributed sensory
timing hypothesis.
PMID- 29343858
TI - Developmental pathways inferred from modularity, morphological integration and
fluctuating asymmetry patterns in the human face.
AB - Facial asymmetries are usually measured and interpreted as proxies to
developmental noise. However, analyses focused on its developmental and genetic
architecture are scarce. To advance on this topic, studies based on a
comprehensive and simultaneous analysis of modularity, morphological integration
and facial asymmetries including both phenotypic and genomic information are
needed. Here we explore several modularity hypotheses on a sample of Latin
American mestizos, in order to test if modularity and integration patterns differ
across several genomic ancestry backgrounds. To do so, 4104 individuals were
analyzed using 3D photogrammetry reconstructions and a set of 34 facial landmarks
placed on each individual. We found a pattern of modularity and integration that
is conserved across sub-samples differing in their genomic ancestry background.
Specifically, a signal of modularity based on functional demands and organization
of the face is regularly observed across the whole sample. Our results shed more
light on previous evidence obtained from Genome Wide Association Studies
performed on the same samples, indicating the action of different genomic regions
contributing to the expression of the nose and mouth facial phenotypes. Our
results also indicate that large samples including phenotypic and genomic
metadata enable a better understanding of the developmental and genetic
architecture of craniofacial phenotypes.
PMID- 29343860
TI - Predicted impact of thermal power generation emission control measures in the
Beijing-Tianjin-Hebei region on air pollution over Beijing, China.
AB - Widespread economic growth in China has led to increasing episodes of severe air
pollution, especially in major urban areas. Thermal power plants represent a
particularly important class of emissions. Here we present an evaluation of the
predicted effectiveness of a series of recently proposed thermal power plant
emission controls in the Beijing-Tianjin-Hebei (BTH) region on air quality over
Beijing using the Community Multiscale Air Quality(CMAQ) atmospheric chemical
transport model to predict CO, SO2, NO2, PM2.5, and PM10 levels. A baseline
simulation of the hypothetical removal of all thermal power plants in the BTH
region is predicted to lead to 38%, 23%, 23%, 24%, and 24% reductions in current
annual mean levels of CO, SO2, NO2, PM2.5, and PM10 in Beijing, respectively.
Similar percentage reductions are predicted in the major cities in the BTH
region. Simulations of the air quality impact of six proposed thermal power plant
emission reduction strategies over the BTH region provide an estimate of the
potential improvement in air quality in the Beijing metropolitan area, as a
function of the time of year.
PMID- 29343861
TI - Sensing Native Protein Solution Structures Using a Solid-state Nanopore:
Unraveling the States of VEGF.
AB - Monitoring individual proteins in solution while simultaneously obtaining
tertiary and quaternary structural information is challenging. In this study,
translocation of the vascular endothelial growth factor (VEGF) protein through a
solid-state nanopore (ssNP) produces distinct ion-current blockade amplitude
levels and durations likely corresponding to monomer, dimer, and higher
oligomeric states. Upon changing from a non-reducing to a reducing condition, ion
current blockage events from the monomeric state dominate, consistent with the
expected reduction of the two inter-chain VEGF disulfide bonds. Cleavage by
plasmin and application of either a positive or a negative NP bias results in
nanopore signals corresponding either to the VEGF receptor recognition domain or
to the heparin binding domain, accordingly. Interestingly, multi-level analysis
of VEGF events reveals how individual domains affect their translocation pattern.
Our study shows that careful characterization of ssNP results elucidates real
time structural information about the protein, thereby complementing classical
techniques for structural analysis of proteins in solution with the added
advantage of quantitative single-molecule resolution of native proteins.
PMID- 29343862
TI - Angiotensin II Overstimulation Leads to an Increased Susceptibility to Dilated
Cardiomyopathy and Higher Mortality in Female Mice.
AB - Heart failure (HF) is associated with high mortality and affects men and women
differently. The underlying mechanisms for these sex-related differences remain
largely unexplored. Accordingly, using mice with cardiac-specific overexpression
of the angiotensin II (ANGII) type 1 receptor (AT1R), we explored male-female
differences in the manifestations of hypertrophy and HF. AT1R mice of both sexes
feature electrical and Ca2+ handling alterations, systolic dysfunction,
hypertrophy and develop HF. However, females had much higher mortality (21.0%)
rate than males (5.5%). In females, AT1R stimulation leads to more pronounced
eccentric hypertrophy (larger increase in LV mass/body weight ratio [+31%], in
cell length [+27%], in LV internal end-diastolic [LVIDd, +34%] and systolic
[LVIDs, +67%] diameter) and dilation (larger decrease in LV posterior wall
thickness, +17%) than males. In addition, in female AT1R mice the cytosolic Ca2+
extrusion mechanisms were more severely compromised and were associated with a
specific increased in Ca2+ sparks (by 187%) and evidence of SR Ca2+ leak.
Altogether, these results suggest that female AT1R mice have more severe
eccentric hypertrophy, dysfunction and compromised Ca2+ dynamics. These findings
indicate that females are more susceptible to the adverse effects of AT1R
stimulation than males favouring the development of HF and increased mortality.
PMID- 29343863
TI - Genetic analyses favour an ancient and natural origin of elephants on Borneo.
AB - The origin of the elephant on the island of Borneo remains elusive. Research has
suggested two alternative hypotheses: the Bornean elephant stems either from a
recent introduction in the 17th century or from an ancient colonization several
hundreds of thousands years ago. Lack of elephant fossils has been interpreted as
evidence for a very recent introduction, whereas mtDNA divergence from other
Asian elephants has been argued to favor an ancient colonization. We investigated
the demographic history of Bornean elephants using full-likelihood and
approximate Bayesian computation analyses. Our results are at odds with both the
recent and ancient colonization hypotheses, and favour a third intermediate
scenario. We find that genetic data favour a scenario in which Bornean elephants
experienced a bottleneck during the last glacial period, possibly as a
consequence of the colonization of Borneo, and from which it has slowly recovered
since. Altogether the data support a natural colonization of Bornean elephants at
a time when large terrestrial mammals could colonise from the Sunda shelf when
sea levels were much lower. Our results are important not only in understanding
the unique history of the colonization of Borneo by elephants, but also for their
long-term conservation.
PMID- 29343864
TI - Electrochemical and Friction Characteristics of Metallic Glass Composites at the
Microstructural Length-scales.
AB - Metallic glass composites represent a unique alloy design strategy comprising of
in situ crystalline dendrites in an amorphous matrix to achieve damage tolerance
unseen in conventional structural materials. They are promising for a range of
advanced applications including spacecraft gears, high-performance sporting goods
and bio-implants, all of which demand high surface degradation resistance. Here,
we evaluated the phase-specific electrochemical and friction characteristics of a
Zr-based metallic glass composite, Zr56.2Ti13.8Nb5.0Cu6.9Ni5.6Be12.5, which
comprised roughly of 40% by volume crystalline dendrites in an amorphous matrix.
The amorphous matrix showed higher hardness and friction coefficient compared to
the crystalline dendrites. But sliding reciprocating tests for the composite
revealed inter-phase delamination rather than preferred wearing of one phase.
Pitting during potentiodynamic polarization in NaCl solution was prevalent at the
inter-phase boundary, confirming that galvanic coupling was the predominant
corrosion mechanism. Scanning vibration electrode technique demonstrated that the
amorphous matrix corroded much faster than the crystalline dendrites due to its
unfavorable chemistry. Relative work function values measured using scanning
kelvin probe showed the amorphous matrix to be more electropositive, which
explain its preferred corrosion over the crystalline dendrites as well as its
characteristic friction behavior. This study paves the way for careful
partitioning of elements between the two phases in a metallic glass composite to
tune its surface degradation behavior for a range of advanced applications.
PMID- 29343865
TI - Targeting murine leukemic stem cells by antibody functionalized mesoporous silica
nanoparticles.
AB - Acute leukemia is initiated and maintained by leukemia stem cells (LSCs) and
therefore there is great interest to develop innovative therapeutic approaches
which target LSCs. Here we show that mesoporous silica nanoparticles (MSNs)
functionalized with succinic anhydride, tagged with an anti-B220 antibody and
loaded with the anthracycline daunorubicin are efficiently incorporated into
murine B220-positive AML LSCs and preferentially kill these cells in comparison
to B220-negative AML LSCs in vitro. Furthermore, short - term treatment of the
AML LSCs with these MSNs before transplant significantly delayed leukemia
development in recipient mice. These data demonstrate that targeting of AML LSCs
can be improved by using functionalized and antigen directed MSNs as carriers for
anti-leukemic drugs.
PMID- 29343866
TI - Identification of JAZ-interacting MYC transcription factors involved in latex
drainage in Hevea brasiliensis.
AB - Hevea brasiliensis Mull. Arg. is one of the most frequently wounded plants
worldwide. Expelling latex upon mechanical injury is a wound response of rubber
trees. However, JA-mediated wound responses in rubber trees are not well
documented. In this work, three JAZ-interacting MYC transcription factors of H.
brasiliensis (termed HbMYC2/3/4) were identified by yeast two-hybrid screening.
HbMYC2/3/4 each showed specific interaction profiles with HbJAZs. HbMYC2/3/4 each
localized in the nucleus and exhibited strong transcriptional activity. To
identify the target genes potentially regulated by HbMYC2/3/4, cis-elements
interacting with HbMYC2/3/4 were first screened by yeast one-hybrid assays; the
results indicated that HbMYC2/3/4 each could bind G-box elements. Additional
analysis confirmed that HbMYC2/3/4 bound the HbPIP2;1 promoter, which contains
five G-box cis-elements, and regulated the expression of reporter genes in yeast
cells and in planta. HbMYC2/3/4 were induced by exogenous JA treatment but
suppressed by ethylene (ET) treatment; in contrast, HbPIP2;1 was positively
regulated by ET but negatively regulated by JA treatment. Given that HbPIP2;1 is
involved in latex drainage, it could be proposed that HbMYC2/3/4 are involved in
the regulation of HbPIP2;1 expression as well as latex drainage, both of which
are coordinated by the JA and ET signalling pathways.
PMID- 29343867
TI - Improving survival of acute-on-chronic liver failure patients complicated with
invasive pulmonary aspergillosis.
AB - The mortality of acute-on-chronic liver failure (ACLF) patients complicated with
invasive pulmonary aspergillosis (IPA) was extremely high. We aimed to explore
prognostic value of the Chronic Liver Failure-Sequential Organ Failure Assessment
(CLIF-SOFA) lung score and to establish an optimal voriconazole regimen for ACLF
patients complicated with IPA. We retrospectively screened hospitalized ACLF
patients in our hospital from July 2011 to April 2016, from which 20 probable IPA
cases were diagnosed. Along with onsets of IPA, deteriorated diseases severity,
especially lung conditions were found in those 20 ACLF patients. It was found
that IPA patients with CLIF-SOFA lung score <2 had better 28-day survival than
those with lung score >1 (11/13 vs 0/7, p < 0.001). Based on plasma voriconazole
concentration measurement, an optimal voriconazole regimen (loading doses: 0.2 g
twice daily; maintenance doses, 0.1 g once daily) was established, which resulted
in rational trough plasma drug concentrations (1-5 MUg/mL), good clinical
outcomes (90-day survival rate of 6/8) and no observed adverse events. In
conclusion, CLIF-SOFA lung score >1 was able to identify ACLF patients
complicated with IPA encountering much higher 28-day mortality. An optimal
voriconazole regimen was safe and effective in our ACLF patients complicated with
IPA.
PMID- 29343868
TI - Galectin-13, a different prototype galectin, does not bind beta-galacto-sides and
forms dimers via intermolecular disulfide bridges between Cys-136 and Cys-138.
AB - During pregnancy, placental protein-13 (galectin-13) is highly expressed in the
placenta and fetal tissue, and less so in maternal serum that is related to pre
eclampsia. To understand galectin-13 function at the molecular level, we solved
its crystal structure and discovered that its dimer is stabilized by two
disulfide bridges between Cys136 and Cys138 and six hydrogen bonds involving
Val135, Val137, and Gln139. Native PAGE and gel filtration demonstrate that this
is not a crystallization artifact because dimers also form in solution. Our
biochemical studies indicate that galectin-13 ligand binding specificity is
different from that of other galectins in that it does not bind beta
galactosides. This is partly explained by the presence of Arg53 rather than His53
at the bottom of the carbohydrate binding site in a position that is crucial for
interactions with beta-galactosides. Mutating Arg53 to histidine does not re
establish normal beta-galactoside binding, but rather traps cryoprotectant
glycerol molecules within the ligand binding site in crystals of the R53H mutant.
Moreover, unlike most other galectins, we also found that GFP-tagged galectin-13
is localized within the nucleus of HeLa and 293 T cells. Overall, galectin-13
appears to be a new type of prototype galectin with distinct properties.
PMID- 29343869
TI - Spatiotemporal allele organization by allele-specific CRISPR live-cell imaging
(SNP-CLING).
AB - Imaging and chromatin capture techniques have provided important insights into
our understanding of nuclear organization. A limitation of these techniques is
the inability to resolve allele-specific spatiotemporal properties of genomic
loci in living cells. Here, we describe an allele-specific CRISPR live-cell DNA
imaging technique (SNP-CLING) to provide the first comprehensive insights into
allelic positioning across space and time in mouse embryonic stem cells and
fibroblasts. With 3D imaging, we studied alleles on different chromosomes in
relation to one another and relative to nuclear substructures such as the
nucleolus. We find that alleles maintain similar positions relative to each other
and the nucleolus; however, loci occupy unique positions. To monitor
spatiotemporal dynamics by SNP-CLING, we performed 4D imaging and determined that
alleles are either stably positioned or fluctuating during cell state
transitions, such as apoptosis. SNP-CLING is a universally applicable technique
that enables the dissection of allele-specific spatiotemporal genome organization
in live cells.
PMID- 29343870
TI - Italian law n. 24/2017 on physicians' criminal liability: a reform that does not
solve the problems of the psychiatric practice
AB - For years psychiatrists have been facing the risk of being prosecuted for
professional liability. One of the reasons for this situation depends on the fact
that professionals cannot rely on clear rules of conduct. Indeed, in psychiatry,
it may happen that a judge considers negligent a conduct not punishable by
another court, as in cases of hospital discharges. In order to solve this
situation, on March 8, 2017 Italian legislators issued the law no. 24. First of
all, it establishes that health care providers must follow the guidelines that
will be published on the website of the High Institute of Health, with the
exception of specific situations on a given case. In the absence of such
guidelines, the good clinical-care practice should be applied (Art. 5). In
addition, if health care providers have met the guidelines as appropriate to the
specific case or, in their absence, to the good clinical-care practice, they
cannot be sentenced for homicide or accidental injury due to incapacity (Art. 6).
The authors analyze these provisions with the aim of verifying if they are
adequate to achieve the purposes that the legislator had set: 1) protecting
patients' health; 2) offering psychiatrists clear rules of conduct in order to
reduce the risk of being subjected to criminal proceedings. The first objective
is endangered by the fact that the law does not indicate the level of the
evidences trustworthiness necessary to make them be considered as binding
guidelines. The second objective appears unreachable. In fact, the law under
consideration states that only incapacity is not punishable, whereas homicide and
lesions caused by negligence or imprudence, even if slight, are considered a
crime. In the psychiatric field, more than in other branches of medicine, charges
normally concern negligence or imprudence. Therefore, this reform does not limit
at all psychiatrists' criminal liability.
PMID- 29343871
TI - [Ulysses contract in psychiatry].
AB - Over the last twenty years we have witnessed a growing focus on the rights of the
ill people. The debate on informed consent and a new redefinition of the
therapeutic relationship is constantly evolving. With this article, we propose a
critical literature review of the so-called "Ulysses contract" or "psychiatric
advance directives". It refers to the will that a subject expresses in writing,
or orally, about the treatments he or she wishes or does not wish to be subject
to if the time comes when it may be impossible to express his/her consent. This
can especially occur in those with psychiatric disorders with serious clinical
involvement and remitting-relapse (typically bipolar disorder, but also chronic
delusional disorders and schizophrenia). In this context, the question is whether
during intercritical periods the patient may or may not leave instructions to
their care-givers. This aspect opens up to a series of interdisciplinary
problems. In this article, we want to show the complexity of this debate from a
clinical, ethical, legal and psychodynamic point of view, emphasizing the
strengths and the major criticisms of the psychiatric advance directives for each
area.
PMID- 29343872
TI - [Duties and liabilities for psychiatrists].
AB - This paper evaluates forensic duties and liabilities for psychiatrists, based on
the current literature and based on our experience over several years of forensic
medicine practice, involving both criminal and civil cases. We evaluated
different scenarios, including cases of patients dangerous to themselves or
others. We highlighted the importance to keep adequate and detailed clinical
records, both in the inpatient and outpatient setting, given the absence of other
objective items (e.g., laboratory records or other instrumental assessments) that
may be of help for the judge and his/her counselors.
PMID- 29343873
TI - A bibliometric analysis of scientific production on atypical antipsychotic drugs
from Italy
AB - Objective: A bibliometric study of peer-reviewed scientific publications on
atypical antipsychotic drugs (AADs) from Italy is herein presented. Methods: We
selected the documents from Scopus database. We applied several bibliometric
indicators of production and dispersion, including Price's Law about the increase
of scientific literature, and Bradford's Law. We also calculated the
participation indexacross different countries. The bibliometric data have also
been correlated with some social and health data sourcing in Italy, such as total
per capita expenditure on health and gross domestic expenditure. Results: A total
of 2949 original documents were published within the period 1972-2015. Our
results state fulfilment of Price's Law, with scientific production showing
exponential growth (r=0.901, as against an r=0.838 after linear adjustment). The
drugs most widely studied were clozapine (257 documents), risperidone (179), and
olanzapine (172). Stratificationinto Bradford zones yielded a nucleus represented
by the Journal of Clinical Psychopharmacology and Rivista di Psichiatria (58
articles, each one). A total of 1091 different journals were evaluated.
Conclusions: The publications on AADs in Italy have undergone exponential growth
over the studied period, which is in line with the progressively burgeoning on
novel AAD releases. No evidence of saturation point was observed.
PMID- 29343874
TI - [Mental Health Recovery Star: features and validation study of the Italian
version].
AB - AIM: Mental Health Recovery Star (MHRS) is an instrument that helps to assess
recovery processes of mental health patients through a collaborative approach.
The aim of the study is to describe the features of the instrument and to report
the results of the Italian validation study. METHODS: The study involved 117
users which were evaluated in two phases. Besides MRHS, HoNOS, WHOQoL-brief, GAF
were used. Acceptability for users and key-workers of the instruments and its
main psychometric properties, as test-retes (ICC) and concurrent validity
(Pearson's correlation coefficient), were evaluated. RESULTS: MHRS showed to have
temporal stability in all its areas. Significant correlations were found between
the MHRS and the most closely related areas of the scales used. Inter-rater
reliability were studied in an unsatisfactory way. MHRS was appreciated and easy
to use. Collaborative evaluations were completed mostly in less than 45 minutes.
CONCLUSIONS: MHRS is an acceptable tool for users and staff-members,
distinguishing itself from the use of useful visual aids; helps to identify the
patient's recovery path and supports a collaborative approach between user and
operator. The results of the psychometric properties of the instrument appeared
promising but not exhaustive. Although further efforts should be addressed to the
implementation of such aspects of the instrument and reflections should be raised
with respect to the traditional methods to detect the complex meaning of recovery
(subjective-objective aspects), the valuable collaborative contribution of MHRS
can not be denied in favoring the user's responsibility and supporting the
professional worker in his role of case manager.
PMID- 29343875
TI - [Trazodone prolonged release in bipolar disorder II-obsessive-compulsive disorder
comorbidity: a case report].
AB - Approximately 21% of patients with bipolar disorder (BD) also have an additional
diagnosis of obsessive-compulsive disorder (OCD). This condition is associated
with a more severe prognosis and complicates the treatment of BD. In our case
report we provide documentary evidence of our experience with trazodone prolonged
release in the treatment of depressive phase in a patient with BD II-OCD
comorbidity. Rationality in the choise of treatment was based on the need to
manage depressive and obsessive symptoms without facilitating hypomania switches.
PMID- 29343878
TI - CXCL14-like Immunoreactivity Exists in Somatostatin-containing Endocrine Cells,
and in the Lamina Propria and Submucosal Somatostatinergic Nervous System of
Mouse Alimentary Tract.
AB - In the present study, we investigated the distribution of CXCL14 immunoreactive
endocrine cells and neurons in mouse alimentary tract by immunohistochemistry.
CXCL14 immunoreactive endocrine cells were found as closed-type cells in the
stomach and open-type cells in the small intestine. The immunostaining of these
endocrine cells corresponded with that of the somatostatin-containing endocrine
cells. Only a few CXCL14 immunoreactive endocrine cells were seen in the large
intestine. CXCL14 immunoreactive fibers were observed in the muscular layer from
the stomach to the rectum with most abundance in the rectum. Many CXCL14
immunoreactive fibers were observed in the lamina propria and submucosal layer
from the duodenum to the rectum with most abundance in the rectum; these fibers
corresponded to the somatostatin-containing nerve fibers. Some CXCL14
immunoreactive neuronal somata that were also immuno-positive for somatostatin,
were noted in the submucosal layer of the rectum. However, the remaining parts of
the alimentary tract presented with almost negligible immunoreactive somata. The
co-localization of CXCL14 and somatostatin suggests that CXCL14 contributes to
the function of somatostatin, which include the inhibition of other endocrine and
exocrine cells and the enteric nervous systems.
PMID- 29343879
TI - CCN3 Expression Marks a Sulfomucin-nonproducing Unique Subset of Colonic Goblet
Cells in Mice.
AB - Intestinal goblet cells are characterized by their unique morphology and
specialized function to secrete mucins. Although it is known that they are a
heterogeneous population of cells, there have been few studies that relate the
expression of a particular gene with functionally distinct subpopulations of
intestinal goblet cells. Here we show that CCN3, a gene encoding a member of the
CCN family proteins, is induced by inhibition of Notch signaling in colonic
epithelial cells and expressed in goblet cells in mice. We demonstrate that CCN3
expression is confined to a subpopulation of goblet cells in the lower crypt of
the proximal and middle colon. In addition, CCN3+ cells in the colon correlate
well with the cells that are positive for alcian blue (AB) staining but negative
for high-iron diamine (HID) staining in histology. We also show that CCN3+ cells,
which are absent in the normal distal colon, transiently and ectopically emerge
in regenerating crypts during the repair phase of DSS-induced colitis model. Our
study thus suggests that CCN3 labels a unique subpopulation of sulfomucin
nonproducing colonic goblet cells that function in both normal and diseased
colonic epithelia.
PMID- 29343880
TI - Novel Application of Loop-mediated Isothermal Amplification for Rapid Detection
of Gene Translocation.
AB - Identification of fusion genes in cancer is essential for pathological diagnosis
and clinical therapy. Although methods for detection of fusion genes, such as
fluorescence in situ hybridization (FISH) and real-time polymerase chain reaction
(PCR), have been developed in last two decades, these methods are not ideal for
detection of these genetic alterations owing to their high cost and time
consuming procedures. In this study, we developed novel application for detection
of gene translocations using loop-mediated isothermal amplification (LAMP). We
verified the amplified DNA products of echinoderm microtubule-associated protein
like 4 and anaplastic lymphoma kinase (EML4-ALK), synaptotagmin and synovial
sarcoma, X breakpoint (SYT-SSX), and immunoglobulin heavy chain gene and B cell
leukemia/lymphoma 2 (IgH/BCL2) by real-time PCR, agarose-gel electrophoresis, and
the naked eye after the LAMP procedure. Fusion genes were detected in samples
diluted 103 times within 60 min. Because of the advantages of rapid
amplification, simple operation, and easy detection without requiring
sophisticated equipment or technical skill, LAMP may have potential applications
as an on-site analytical approach in hospitals for pathological diagnosis and
decision making regarding appropriate therapeutic approachs.
PMID- 29343881
TI - Validation of Anti-CSPalpha, SNAP25, Tyrosine Hydroxylase, Ubiquitin, Cleaved
Caspase 3, and pSer PKC Motif Antibodies for Utilization in Western Blotting.
AB - There are many commercial antibodies with little information provided by their
suppliers as to their reliability. Accordingly, commercial antibodies require
proper validation before being used in scientific research. In this study, we
validated several commercial antibodies, including anti-CSPalpha, SNAP25,
tyrosine hydroxylase, ubiquitin, cleaved caspase 3, and pSer PKC motif. Anti
CSPalpha, SNAP25, and tyrosine hydroxylase antibodies could detect their
endogenous target proteins with some degree of cross-reactivity. Furthermore,
clear SNAP25 staining was observed with SNAP25 antibody. Antibodies directed
against ubiquitin, cleaved caspase 3, and pSer PKC motif could detect poly
ubiquitination, apoptosis, and phosphorylation, respectively.
PMID- 29343882
TI - Can productivity and profitability be enhanced in intensively managed cereal
systems while reducing the environmental footprint of production? Assessing
sustainable intensification options in the breadbasket of India.
AB - In the most productive area of the Indo-Gangetic Plains in Northwest India where
high yields of rice and wheat are commonplace, a medium-term cropping system
trial was conducted in Haryana State. The goal of the study was to identify
integrated management options for further improving productivity and
profitability while rationalizing resource use and reducing environmental
externalities (i.e., "sustainable intensification", SI) by drawing on the
principles of diversification, precision management, and conservation
agriculture. Four scenarios were evaluated: Scenario 1 - "business-as-usual"
[conventional puddled transplanted rice (PTR) followed by (fb) conventional-till
wheat]; Scenario 2 - reduced tillage with opportunistic diversification and
precision resource management [PTR fb zero-till (ZT) wheat fb ZT mungbean];
Scenario 3 - ZT for all crops with opportunistic diversification and precision
resource management [ZT direct-seeded rice (ZT-DSR) fb ZT wheat fb ZT mungbean];
and Scenario 4 - ZT for all crops with strategic diversification and precision
resource management [ZT maize fb ZT wheat fb ZT mungbean]. Results of this five
year study strongly suggest that, compared with business-as-usual practices, SI
strategies that incorporate multi-objective yield, economic, and environmental
criteria can be more productive when used in these production environments. For
Scenarios 2, 3, and 4, system-level increases in productivity (10-17%) and
profitability (24-50%) were observed while using less irrigation water (15-71%
reduction) and energy (17-47% reduction), leading to 15-30% lower global warming
potential (GWP), with the ranges reflecting the implications of specific
innovations. Scenario 3, where early wheat sowing was combined with ZT along with
no puddling during the rice phase, resulted in a 13% gain in wheat yield compared
with Scenario 2. A similar gain in wheat yield was observed in Scenario 4 vis-a
vis Scenario 2. Compared to Scenario 1, wheat yields in Scenarios 3 and 4 were 15
17% higher, whereas, in Scenario 2, yield was either similar in normal years or
higher in warmer years. During the rainy (kharif) season, ZT-DSR provided yields
similar to or higher than those of PTR in the first three years and lower (11
30%) in Years 4 and 5, a result that provides a note of caution for interpreting
technology performance through short-term trials or simply averaging results over
several years. The resource use and economic and environmental advantages of DSR
were more stable through time, including reductions in irrigation water (22-40%),
production cost (11-17%), energy inputs (13-34%), and total GWP (14-32%). The
integration of "best practices" in PTR in Scenario 2 resulted in reductions of
24% in irrigation water and 21% in GWP, with a positive impact on yield (0.9
t/ha) and profitability compared to conventional PTR, demonstrating the power of
simple management changes to generate improved SI outcomes. When ZT maize was
used as a diversification option instead of rice in Scenario 4, reductions in
resource use jumped to 82-89% for irrigation water and 49-66% for energy inputs,
with 13-40% lower GWP, similar or higher rice equivalent yield, and higher
profitability (27-73%) in comparison to the rice-based scenarios. Despite these
advantages, maize value chains are not robust in this part of India and public
procurement is absent. Results do demonstrate that transformative opportunities
exist to break the cycle of stagnating yields and inefficient resource use in the
most productive cereal-based cropping systems of South Asia. However, these SI
entry points need to be placed in the context of the major drivers of change in
the region, including market conditions, risks, and declining labor availability,
and matching with the needs and interests of different types of farmers.
PMID- 29343883
TI - Magnetoelectric effect in nanogranular FeCo-MgF films at GHz frequencies.
AB - The magnetoelectric effect is a key issue for material science and is
particularly significant in the high frequency band, where it is indispensable in
industrial applications. Here, we present for the first time, a study of the high
frequency tunneling magneto-dielectric (TMD) effect in nanogranular FeCo-MgF
films, consisting of nanometer-sized magnetic FeCo granules dispersed in an MgF
insulator matrix. Dielectric relaxation and the TMD effect are confirmed at
frequencies over 10 MHz. The frequency dependence of dielectric relaxation is
described by the Debye-Frohlich model, taking relaxation time dispersion into
account, which reflects variations in the nature of the microstructure, such as
granule size, and the inter-spacing between the granules that affect the
dielectric response. The TMD effect reaches a maximum at a frequency that is
equivalent to the inverse of the relaxation time. The frequency where the peak
TMD effect is observed varies between 12 MHz and 220 MHz, depending on the
concentration of magnetic metal in the nanogranular films. The inter-spacing of
the films decreases with increasing magnetic metal concentration, in accordance
with the relaxation time. These results indicate that dielectric relaxation is
controlled by changing the nanostructure, using the deposition conditions. A
prospective application of these nanogranular films is in tunable impedance
devices for next-generation mobile communication systems, at frequencies over 1
GHz, where capacitance is controlled using the applied magnetic field.
PMID- 29343885
TI - The curriculum: What is changing?
PMID- 29343884
TI - Neutral Sphingomyelinase Behaviour in Hippocampus Neuroinflammation of MPTP
Induced Mouse Model of Parkinson's Disease and in Embryonic Hippocampal Cells.
AB - Neutral sphingomyelinase is known to be implicated in growth arrest,
differentiation, proliferation, and apoptosis. Although previous studies have
reported the involvement of neutral sphingomyelinase in hippocampus
physiopathology, its behavior in the hippocampus during Parkinson's disease
remains undetected. In this study, we show an upregulation of inducible nitric
oxide synthase and a downregulation of neutral sphingomyelinase in the
hippocampus of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP-) induced
mouse model of Parkinson's disease. Moreover, the stimulation of neutral
sphingomyelinase activity with vitamin 1,25-dihydroxyvitamin D3 reduces
specifically saturated fatty acid sphingomyelin by making sphingomyelin a less
rigid molecule that might influence neurite plasticity. The possible biological
relevance of the increase of neutral sphingomyelinase in Parkinson's disease is
discussed.
PMID- 29343886
TI - Prof. Narendra J. Pandya.
PMID- 29343887
TI - Synovial tuberculosis of the hand: An ancient disease in an unusual localisation.
AB - Background: Tuberculosis is the most prevalent infectious disease in the world.
It is mainly caused by Mycobacterium tuberculosis. Osteoarticular tuberculosis
represents 1%-3%. Tenosynovitis is the most common form of the disease in the
hand. Aims: The aim of this study is to present an update of synovial
tuberculosis. Materials and Methods: The authors present a literature review, the
clinical and surgical management and case reports. Results: The outcomes were
satisfactory and were not report complications. Conclusions: Early diagnosis,
surgical transection of the transverse carpal ligament, debridement and complete
excision of the infected synovium may be required, along with antituberculosis
drugs. Knowledge of this disease in the hand can provide a better diagnosis and
outcome.
PMID- 29343888
TI - Medial femoral condyle vascularised corticoperiosteal graft: A suitable choice
for scaphoid non-union.
AB - Introduction: Scaphoid fractures are not very common and frequently remain
undiagnosed, presenting in non-union and persistent wrist pain. Options for
scaphoid fracture treatment have been described over several decades, however,
none with an optimal solution to achieve union along with good hand function. We
describe here, the use of vascularised corticoperiosteal bone grafts from the
medial femoral condyle (MFC) as a solution for the difficult problem of scaphoid
fracture non-union. Materials and Methods: This series has 11 patients with non
union following a scaphoid fracture treated over 18 months ranging from January
2014 to January 2016 using a vascularised corticoperiosteal graft from the MFC.
Bone graft fixation was done using K-wires and anastomosis was done with the
radial vessels. Results: There were no cases of flap loss. Time of union was an
average 3 months. All patients had a full range of movements. Discussion: MFC is
an ideal site for harvesting vascularised corticoperiosteal grafts providing a
large surface of tissue supplied by a rich periosteal plexus from the descending
genicular artery. No significant donor site morbidities have been reported in any
series in the past. The well-defined anatomy helps in a rather simple dissection.
Corticoperiosteal grafts have a high osteogenic potential and hence, this
vascularised graft seems ideal for small bone non-unions. Conclusion: Thin,
pliable and highly vascularised corticocancellous grafts can be obtained from the
MFC as an optimal treatment option for scaphoid non-unions.
PMID- 29343889
TI - First two bilateral hand transplantations in India (Part 1): From vision to
reality.
AB - Introduction: Vascularized composite tissue allotransplantation is a relatively
new concept, which was unavailable in the Indian subcontinent till a bilateral
hand transplant was carried out successfully in January 2015. Materials and
Methods: The setting up of the transplant programme involved obtaining legal
clearances, creating public awareness, harnessing the institutional facilities,
drawing up protocols, assembling the surgical team, managing immunological
issues, rehabilitation and preparing the ancillary services. Results: Both, the
first and second bilateral hand transplants were resounding successes with both
the recipients getting back to their original daily routines. Conclusions: The
organisation of the hand transplant programme was a large task, which
necessitated intensive planning, and cooperation from various teams within and
outside the institution. Exemplary team-work was the key to the phenomenal
success of these path breaking endeavors in the subcontinent.
PMID- 29343890
TI - First two bilateral hand transplantations in India (Part 2): Technical details.
AB - Introduction: This article deals with two patients who underwent bilateral hand
transplantation following amputation of both upper limbs at the distal third of
the foream. Materials and Methods: The first patient had a history of loss of
hands in a train accident , with possiblity of a run over element during the
injury. The second patient lost his both hands in a mine blast. The preoperative
work up included detailed clinical and psychological evaluation. The donor
retrieval was similar in both the cases and the donors were housed in our own
instittution. The donor preparation, recipient preparation and the transplant
procedure was similar except for the need of primary tendon transfers in the left
hand of the first patient. Results: The first patient needed a free flap transfer
to cover compromised skin flap on the left hand on the second day. The second
hand transplant was uneventful. Both the recipients are now back to their normal
daily routines. Conclusions: Hand transplantation is a potentially life altering
procedure, but to optimise the results, it is imperative that there is a
meticulous planning and diligent execution with utmost importance to the detail
coupled with a synchronised team effort.
PMID- 29343891
TI - First two bilateral hand transplantations in India (Part 3): Rehabilitation and
immediate outcome.
AB - Introduction: This report covers the strategies adopted for rehabilitation for
the first and second dual hand transplants performed in India. Materials and
Methods: The team, under a trained physiatrist, including physiotherapy and
occupational therapy personnel, was involved in the management of both these
patients. The management protocol was developed considering previous reports as
well as our management strategies in the rehabilitation of the replanted hands.
The involvement of the team with the patients started in the 1st week itself and
continued on a daily basis for the entire year. Results: Outcome analysis was
performed at 6 months and 1 year using the disability of shoulder and hand
evaluation and hand transplant scoring system. Functional magnetic resonance
imaging was done at the end of 1 year to assess the cortical integration of the
transplanted hand. Conclusion: Despite more than 110 hands being transplanted
worldwide, hand transplant remains an experimental procedure. It is still not
considered the "standard of care" for hand amputees. Outcome analyses performed
worldwide do indicate that the procedure can provide a substantial improvement in
the quality of life for the hand amputee, especially the bilateral amputees.
PMID- 29343892
TI - First two bilateral hand transplantations in India (Part 4): Immediate post
operative care, immunosuppression protocol and monitoring.
AB - Introduction: Being able to counter immune-mediated rejection has for decades
been the single largest obstacle for the progress of vascular composite
allotransplantation (VCA). The human immune system performs the key role of
differentiating the 'self ' from the 'non-self '. This, although is
quintessential to eliminate or resist infections, also resists the acceptance of
an allograft which it promptly recognises as 'non-self'. Materials and Methods:
Pre-operative evaluation of the recipient evaluation included immunological
assessment in the form of panel reactive antibodies (PRA), human leucocyte
antigen (HLA) typing, donor-specific antibody detection assays (DSA) and
complement-dependent cytotoxicity assays (CDC). Induction immunosuppression was
by thymoglobulin and the maintenance by the standard triple-drug therapy.
Results: Both the recipients were managed by the standard triple drug therapy and
have had only minor episodes of rejections thus far which have been managed
appropriately. Discussion: Induction immunosuppression was by thymoglobulin and
the maintenance by the standard triple-drug therapy. Various groups have tried
various other formulations and regimes as well. Conclusion: A comprehensive plan
has to be drawn up for immunological screening, selection and the post-operative
immunosuppressant usage. The ultimate goal of these immunosuppression modalities
is to achieve a state of donor-specific tolerance.
PMID- 29343893
TI - Assessment of perfusion of free flaps used in head and neck reconstruction using
pulsatility index.
AB - Objective: To detect venous or arterial obstruction in the pedicle of a free flap
we can monitor resistance in the flap bed which is reflected in Pulsatility Index
(PI) Therefore if we detect change in the values of the PI in these flaps then we
can detect complications in flap due to vascular insufficiency early. Materials
and Methods: Seven patients of Free Fibular Flap Reconstruction and ten patients
of Free Radial Forearm Flap reconstruction were evaluated over a period of 18
months. In the pre op we recorded PI of Radial and Peroneal artery using colour
doppler study. In the Post Operative Period 2 readings of PI at the anastomotic
site were taken on Day 1 and Day 7. Results: Both Free Radial Forearm and Free
Fibula flaps which were healthy (n = 15) showed a significant decrease in PI
values on first Post Op day as compared to Pre Op. Also there was a significant
fall in PI on Post Op Day 7 as compared to post op Day 1 (P < 0.05) in these
flaps. The flaps developing complications (n = 2) had significantly higher Day 1
Post op PI readings as compared to healthy flaps (P < 0.05). Conclusion: PI is an
objective index which can indicate changes in perfusion of free flaps used in
Head and Neck reconstruction based on which we can predict if a flap is
susceptible to circulatory compromise.
PMID- 29343894
TI - Primary unilateral cleft lip nasal deformity repair using V-Y-Z plasty: An
anthropometric study.
AB - Background: Secondary nose deformity after unilateral cleft lip repair is a
common problem. Loss of tip projection on the cleft side of unilateral cleft lip
nasal deformity can be difficult to correct due to lack of adequate support. The
purpose of this study is to evaluate the surgical outcome after using V-Y-Z
plasty to address unilateral cleft lip nasal deformities. Methods: A cross
sectional study of one surgeon's outcome of 58 performed primary complete
unilateral cleft lip nasal deformity repairs. All these patients met the study
criterion of having anthropometric measurements at the cleft and non-cleft side
of the nose performed at least 1 year postoperatively. Results: Since 2012, 32
consecutive patients have undergone primary anatomical repair of the cleft nasal
deformity in patients with a complete unilateral cleft. We have not found
statistically significant differences between the cleft and non-cleft nostril
dome height and columella length measured at least 1 year postoperatively.
Conclusions: The findings suggest that the V-Y-Z plasty is a good alternative to
create a more symmetric nasal tip in patients with primary unilateral cleft lip
nasal deformity. Additional studies are required to evaluate functional and long
term outcomes after primary rhinoplasty in patients with unilateral cleft lip.
PMID- 29343895
TI - Why borrow from Peter when Paul can afford it? Reverse homodigital artery flap
for fingertip reconstruction.
AB - Background: Fingertip injuries that are complicated by pulp loss, bone or tendon
exposure will need a flap cover. Cross finger flap is commonly used to cover such
defects. However, patients are apprehensive about injuring the uninjured finger
as a donor site. Reverse homodigital artery flap (RHAF) can provide reliable
vascularised cover to such defects. Aims: This study aims to assess the
functional and aesthetic outcomes along with the patient satisfaction of RHAFs
done for fingertip defects. Materials and Methods: RHAFs done in 18 patients
operated between August 2015 and October 2016 were retrospectively analysed on
flap survival, sensory recovery, range of movements, hypersensitivity, cold
intolerance, flexion contracture and donor site morbidity. Results: Seventeen of
the 18 flaps done survived completely. One flap had partial necrosis of 3 mm that
healed conservatively. Middle finger of the right hand was the most commonly
injured finger. Touch, pain and pressure sensations recovered in 8-12 weeks. Two
point discrimination was 4.5 mm at 6 months. The deficit of 5 degrees s was
present at distal interphalangeal joint during active flexion at 6 months. Cold
intolerance and flexion contracture were not seen and 2 instances of
hypersensitivity at 2 months got cured conservatively after 4 months. Overall
satisfaction of patients was 8/10. Conclusion: RHAF provides single staged well
vascularised cover for fingertip injuries with good sensory recovery without
damaging the adjacent uninjured finger. Hence, it can be a reliable flap for
fingertip reconstruction in selected cases.
PMID- 29343896
TI - Management of vascular anomalies: Review of institutional management algorithm.
AB - Introduction: Vascular anomalies are congenital lesions broadly categorised into
vascular tumour (haemangiomas) and vascular dysmorphogenesis (vascular
malformation). The management of these difficult problems has lately been
simplified by the biological classification and multidisciplinary approach. To
standardise the treatment protocol, an algorithm has been devised. The study aims
to validate the algorithm in terms of its utility and presents our experience in
managing vascular anomalies. Materials and Methods: The biological classification
of Mulliken and Glowacki was followed. A detailed algorithm for management of
vascular anomalies has been devised in the department. The protocol is being
practiced by us since the past two decades. The data regarding the types of
lesions and treatment modality used were maintained. Results and Conclusion: This
study was conducted from 2002 to 2012. A total of 784 cases of vascular anomalies
were included in the study of which 196 were haemangiomas and 588 were vascular
malformations. The algorithmic approach has brought an element of much-needed
objectivity in the management of vascular anomalies. This has helped us to define
the management of particular lesion considering its pathology, extent and
aesthetic and functional consequences of ablation to a certain extent.
PMID- 29343897
TI - Contralateral lumbo-umbilical flap: A versatile technique for volar finger
coverage.
AB - Background: While contemplating any difficult soft tissue reconstruction, patient
comfort and compliance is of paramount importance. Reconstruction of the volar
aspect of fingers and hand by the ipsilateral pedicled flaps (groin flap,
abdominal flaps) is demanding as the flap inset is difficult for the surgeon and
very uncomfortable for the patient. This often leads to flap complications. For
the comfort of the patient, better compliance and ease of complete inset, we
planned to manage soft tissue defects of the volar aspect of fingers and hand by
a new contralateral pedicled lumbo-umbilical flap. This flap is based on the
paraumbilical perforators of deep inferior epigastric artery. Materials and
Methods: The contralateral pedicled lumbo-umbilical flap was used in eight
patients with high-tension electrical burn injuries involving the volar aspect of
fingers and hand. The patients were closely observed for first 6 weeks for any
flap or donor site complications and then followed monthly to assess donor and
recipient site characteristics for 6 months to 2 years. Results and Conclusion:
Large flaps up to 8 cm * 16 cm were raised. All but one flaps survived
completely. All patients were mobilised within 48 h and five were discharged in
less than a week after initial inset. The flap is reliable, easy to harvest and
easy to inset on the volar aspect of fingers. The arm is positioned in a very
comfortable position. The main disadvantage, however, is a conspicuous abdominal
scar.
PMID- 29343898
TI - Assessment of temporomandibular joint dysfunction in condylar fracture of the
mandible using the Helkimo index.
AB - Introduction: Condylar fractures of the mandible are functionally important
fractures as the condyle of the mandible being a part of the temporomandibular
joint (TMJ) and can lead to TMJ dysfunction if not properly treated. Materials
and Methods: This was a cross-sectional study of a total of 33 treated patients
with fracture of the mandibular condyle who underwent examination as per the
Helkimo index. Their dysfunction was quantified and clinicoepidemiological
characteristics were assessed. It was found that majority of our patients were
young males involved in a two-wheeler accident. All patients underwent
intermaxillary fixation as the minimum treatment and 30% underwent open reduction
and internal fixation in addition. Results: There was no statistically
significant association between the degree of clinical dysfunction and factors
such as age, mechanism of injury, type of condyle fracture, presence of other
mandible fractures, and surgical procedure. However, dislocation of the
mandibular condyle was found to be a negative prognostic factor and all these
patients had some degree of dysfunction. Conclusion: The overall prevalence of
TMJ dysfunction according to the Helkimo index was 90%. About 61% of patients had
mild dysfunction (Di1) and 30% had moderate dysfunction (Di2). None of the
patients had severe dysfunction. To conclude, the Helkimo index is a simple,
effective, inexpensive, reliable screening index to assess TMJ dysfunction in
condylar fractures of mandible.
PMID- 29343899
TI - Flap cover in a patient with severe haemophilia type A.
AB - Haemophilia A is a rare haematological disorder due to deficiency of Factor VIII,
causing an abnormal coagulation response to injury. In severe haemophilia A,
Factor VIII level is < 1%, often manifesting with spontaneous bleeding into
joints. Judicious use of recombinant Factor VIII therapy to maintain adequate
levels in the intraoperative, immediate and late post-operative periods, together
with adjuvant pro-coagulants, can ensure a safe outcome following surgery. We
describe the successful management of one such patient suffering from Marjolin's
ulcer of the right gluteal region, who needed wide local excision followed by
flap cover. A protocol for management of such patients is also suggested. This is
the first such case report from the Indian subcontinent, with only a few such
published reports from the West.
PMID- 29343900
TI - Direct electrical injury to brachial plexus.
AB - Electrical current can cause neurological damage directly or by conversion to
thermal energy. However, electrical injury causing isolated brachial plexus
injury without cutaneous burns is extremely rare. We present a case of a 17-year
old boy who sustained accidental electrical injury to left upper extremity with
no associated entry or exit wounds. Complete motor and sensory loss in upper limb
were noted immediately after injury. Subsequently, the patient showed partial
recovery in muscles around the shoulder and in ulnar nerve distribution at 6
months. However, there was no improvement in muscles supplied by
musculocutaneous, median and radial nerves. On exploration at 6 months after
trauma, injury to the infraclavicular plexus was identified. Reconstruction of
musculocutaneous, median and radial nerves by means of sural nerve cable grafts
was performed. The patient has shown excellent recovery in musculocutaneous nerve
function with acceptable recovery of radial nerve function at 1-year post-injury.
PMID- 29343901
TI - A modified Lund and Browder chart.
PMID- 29343902
TI - An axillary port with concealed scar for liposuction of gynaecomastia.
PMID- 29343903
TI - Whose evidence do we follow?
PMID- 29343904
TI - Medical Council of India's amended qualifications for Indian medical teachers:
Well intended, yet half-hearted.
PMID- 29343905
TI - What's inside.
PMID- 29343906
TI - Round up.
PMID- 29343907
TI - New therapies in nonmuscle invasive bladder cancer treatment.
AB - Introduction: Nonmuscle invasive bladder cancer (NMIBC) remains a very
challenging disease to treat with high rates of recurrence and progression
associated with current therapies. Recent technological and biological advances
have led to the development of novel agents in NMIBC therapy. Methods: We
reviewed existing literature as well as currently active and recently completed
clinical trials in NMIBC by querying PubMed.gov and clinicaltrials.gov. Results:
A wide variety of new therapies in NMIBC treatment are currently being developed,
utilizing recent developments in the understanding of immune therapies and cancer
biology. Conclusion: The ongoing efforts to develop new therapeutic approaches
for NMIBC look very promising and are continuing to evolve.
PMID- 29343909
TI - Decline in semen parameters from 2000 to 2016 among Bangladeshi men attending a
tertiary care hospital.
AB - Introduction: The objective of this study was to analyze longitudinal changes in
sperm parameters of Bangladeshi men. We hypothesized that semen parameters
declined for this population. Methods: We retrospectively analyzed semen data
from men aged 18-64 years who sought care for general sperm quality or updates on
fertility status at an infertility clinic in Dhaka, Bangladesh, from January 2000
to June 2016 (n = 13,953). Samples with incomplete data were excluded (n = 143).
The WHO normal criteria and semen analysis procedures were used to evaluate
parameters of the remaining 13,810 specimens. Samples with missing values on
sperm concentration (n = 6187) were excluded from concentration analyses. Age and
duration of abstinence at testing were recorded and adjusted for. Data were
imported into SAS(r) 9.4 statistical software. Temporal significance was
investigated using one-way ANOVA for motility parameters and Chi-square test for
raw concentration. Logistic regression analyzed the effects of confounders on
azoospermia and raw concentration, while median regression modeling adjusted
confounders for concentration, total motility, and rapid linear (RL) motility.
Results: Age distribution was significantly correlated with annual parameter
changes (concentration, total motility, and RL motility [P < 0.0001]). Adjusted
total motility and RL motility declined by 20% from their maximum values to end
of the study (P < 0.0001). Raw concentration lacked clear trends and was
unaffected by adjustment. Azoospermia increased by 18% between the 2000-2010 and
2011-2016 participants (odds ratio = 0.16 [0.14-0.16]). Conclusion: In agreement
with the hypothesis, Bangladeshi males attending this clinic have experienced
decline in semen parameters (total motility and RL motility) and increased
frequency of azoospermia.
PMID- 29343908
TI - PET-CT and PET-MR in urological cancers other than prostate cancer: An update on
state of the art.
AB - Hybrid positron emission tomography with computed tomography (PET/CT) and
magnetic resonance imaging (PET/MRI) have enabled the combination of morphologic
and functional imaging with the promise of providing better information in
guiding therapy. Further advance has been made in the past decade with the
development of newer radiotracers and optimization of the technical aspects. We
performed a search in PubMed, Scopus, and Google Scholar for peer-reviewed
literature concerning the advances and newer developments in the imaging of
nonprostate urologic cancers between 2005 and 2017. This review aims at
summarizing the current evidence on PET imaging in nonprostate urologic cancers
and their impact on the diagnosis, staging, prognostication, response assessment,
and restaging of these malignancies. However, much of the evidence is still in
infancy and has not been incorporated into routine management or the practice
guidelines of National Comprehensive Cancer Network or European Society for
Medical Oncology (ESMO).
PMID- 29343910
TI - Urodynamic outcomes of tamsulosin in the treatment of primary bladder neck
obstruction in men.
AB - Introduction: Alpha blockers are widely used in the treatment of primary bladder
neck obstruction; however, evidence for objective urodynamic efficacy is scarce.
We studied the effect of the uroselective alpha1-blocker tamsulosin on urodynamic
parameters in male patients with type I primary bladder neck obstruction.
Methods: A single center prospective observational study was carried out from
July 2013 to February 2015. Male patients (18-50 years) with type 1 primary
bladder neck obstruction were recruited. Selected patients were started on tablet
tamsulosin 0.4 mg once daily for 3 months. International prostate symptom score
(IPSS), uroflow and urodynamic studies were done pre- and post-treatment. Primary
outcome was decreased in minimum detrusor pressure at maximum flow rate by 15%.
Wilcoxon-matched pair signed-rank test was used. Results: Of 39 patients
recruited, 21 patients completed the follow-up as per protocol and were analyzed.
Mean age was 41 years. 57% patients achieved the primary outcome (median detrusor
pressure pre- and post-treatment were 71 and 56 cm of water, P < 0.001).
Similarly, median values for bladder outlet obstruction index (BOOI) and IPSS
decreased from 59 to 38 (P < 0.001) and 22 to 12 (P < 0.001), respectively.
Median maximum flow rate increased from 8 to 10 ml (P = 0.05). Pretreatment BOOI
of >60 was associated with poor outcomes. Conclusions: Tamsulosin 0.4 mg once a
day is effective in reducing bladder outlet obstruction on pressure flow studies
in patients with primary bladder neck obstruction type 1.
PMID- 29343911
TI - Oncologic outcomes in patients with nonurothelial bladder cancer.
AB - Introduction: We aimed to evaluate the relative prognostic impact of the most
common variant histologies on disease-specific survival (DSS) in patients
undergoing radical cystectomy. Materials and Methods: The Surveillance,
Epidemiology, and End Result database was used to identify patients who underwent
radical cystectomy for bladder cancer from 1990 to 2007. Patients with urothelial
cell carcinoma (UCC), squamous cell carcinoma (SCC), adenocarcinoma (AC),
sarcoma, small cell carcinoma, signet ring carcinoma, and spindle cell carcinoma
were included in the study. Multivariable analysis was performed using Cox
proportional hazards model to assess independent predictors of disease-specific
survival (DSS). Mortality rates were estimated using Kaplan-Meier analyses.
Results: A total of 14,130 patients met inclusion criteria with the following
histologies: UCC (90.1%), SCC (4.6%), AC, (2.3%), sarcoma (0.8%), small cell
carcinoma (0.8%), signet ring carcinoma (0.5%), and spindle cell carcinoma
(0.9%). Three-year DSS was most favorable in patients with UCC (63.7%; 95%
confidence interval [62.9%-64.8%]) and AC (65.3% [59.3%-70.6%]), whereas 3-year
DSS was the least favorable for small cell carcinoma (41.6% [31.3%-51.6%]) and
sarcoma (45.4% [35.1%-55.1%]). In the multivariable analysis, independent
predictors of DSS were age, marital status, grade, T-stage, N-stage, and variant
histology. With respect to UCC, there was an increased risk of disease-specific
death associated with all variants except AC. Sarcoma and spindle cell carcinoma
were associated with the highest risk of death. Conclusions: With the exception
of AC, the most common variant bladder cancer histologies are all independently
associated with worse DSS relative to UCC in patients undergoing radical
cystectomy.
PMID- 29343912
TI - Lateral percutaneous nephrolithotomy: A safe and effective surgical approach.
AB - Introduction: Percutaneous nephrolithotomy (PCNL) is traditionally performed with
the patient in the prone position for large renal calculi. However, anesthetic
limitations exist with the prone position. Similarly, the supine position is
associated with poorer ergonomics due to the awkward downward position of the
renal tract, a smaller window for percutaneous puncture, and a higher risk of
anterior calyx puncture. This study aimed to demonstrate the feasibility and
safety of lateral-PCNL in managing large renal calculi without the disadvantages
of prone and supine positions. Methods: Retrospectively, 347 lateral-PCNL cases
performed from July 2001 to July 2015 were examined. the patient's thorax,
abdomen, and pelvis were positioned over a bridge perpendicular to a "broken"
table, creating an extended lumbodorsal space. The procedure was evaluated in
terms of stone clearance at 3 months' postprocedure, operative time, and
complications. Results: Primary stone clearance was achieved in 82.7% of
patients. The mean operating time was 97 min. The average time taken to establish
the tract and mean radiation time were 4.5 min and 6.93 min, respectively. In
total, 2.3% of patients required postoperative transfusion, and 13.5% of patients
had postoperative fever. There was one case of hydrothorax, but no bowel
perforation. Conclusions: Our lateral-PCNL technique allows for effective stone
clearance due to good stone ergonomics and it should be considered as a safe
alternative even in the most routine procedures.
PMID- 29343913
TI - Comparison of RENAL, PADUA, and C-index scoring systems in predicting
perioperative outcomes after nephron sparing surgery.
AB - Introduction and Objective: The RENAL, PADUA and centrality index (C-index)
nephrometry scoring systems (SS) have been individually evaluated for their role
in predicting trifecta outcomes after nephron-sparing surgery (NSS). However,
there is little data on their comparative superiority. The present study was
designed to evaluate the predictive value of three SS and to assess interobserver
reliability. Materials and Methods: Fifty patients undergoing NSS at our center
between January 2014 and April 2016 were included in the study. The demographic
details were noted. Images (computed tomography [CT] scans or magnetic resonance
imaging) were reviewed by a urologist and a radiologist independently and RENAL,
PADUA, and C-index were calculated. The correlation between these scoring system
and trifecta outcomes were calculated. Results: The RENAL and PADUA score did not
correlate with any of the perioperative parameters. However, C-index had a
significant correlation with operative time (OT) (P = 0.02) and trifecta outcomes
(P < 0.05). There was an excellent concordance between the two observers in
scoring the RENAL score (alpha = 0.915; intraclass correlation coefficient [ICC]
= 0.814) and PADUA score (alpha = 0.816; ICC = 0.689 [P < 0.001]). There was
lesser although acceptable concordance in the calculation of C-index (ICC -0.552;
alpha -0.711). Conclusions: There is good correlation among all the 3 SS. C-index
has lower reproducibility due to difficult mathematical calculation but
correlated best with trifecta outcomes.
PMID- 29343914
TI - Symptomatic lower urinary tract dysfunction in sacral agenesis: Potentially high
risk?
AB - Introduction: Sacral agenesis (SA) is a caudal regression anomaly that can cause
neurogenic bladder but is not generally recognized as high risk. We studied the
clinical presentation, upper urinary tract, bone and spine abnormalities, and
urodynamic findings in patients with SA and compared them with related high-risk
conditions, anorectal malformation (ARM), and cloacal malformation. Materials and
Methods: Patient records between May 2011 and December 2015 were identified and
grouped into isolated SA without an overt anomaly (Group I), SA with overt caudal
regression anomalies (Group II), and ARM or cloacal malformation without the SA
(Group III). Distribution of clinical and urodynamic findings and factors
associated with reduced eGFR were tested with rank sum test, t-test, and
unadjusted odds (P < 0.05 significant) using R statistical program (version
3.1.3). Results: Of 605 neurogenic bladder patients treated in the study period,
39 fulfilled the inclusion criteria. 12 were Group I, 5 Group II, and 22 Group
III. Long-standing lower urinary symptoms were noted in all SA patients. Group I
patients were older (14.5 years vs. 6 years and 5 years for II and III). Patients
with SA (Group I and II) had poor compliance (6.7 ml/cmH2O, interquartile range
[IQR] 4-13.6 ml/cmH2O), reduced age-adjusted bladder capacity (59%, IQR 22-85%),
elevated end-fill pressure (22 cmH2O, IQR 11-28 cmH2O), hydronephrosis (88%), and
reduction in eGFR (29%), all comparable to Group III. Most had Renshaw type II SA
and tethered spinal cord rather than wedge-shaped termination. Limitations
include small numbers and significant selection bias. Conclusions: Symptomatic
neurogenic bladder due to SA may cause renal damage similar to ARM but often
eludes diagnosis.
PMID- 29343915
TI - Impact of learning curve on the perioperative outcomes following robot-assisted
partial nephrectomy for renal tumors.
AB - Introduction: Robot-assisted partial nephrectomy (RAPN) is an established,
minimally invasive technique to treat patients with renal masses. The aim of this
study was to assess the learning curve (LC) of RAPN, evaluate its impact on
perioperative outcomes following RAPN and to study the role of surgeon experience
in achieving "trifecta" outcomes following RAPN. Methods: We prospectively
analyzed the clinical and pathological outcomes of 108 consecutive patients who
underwent RAPN for renal tumors from January 2012 to December 2016 by a
laparoscopy trained surgeon with no prior robotic experience. We used warm
ischemia time (WIT) <20 min, operative time <120 min, and blood loss <100 ml as
endpoints for plotting the LCs. Trifecta was analyzed in relation to our LC.
Results: Surgeon experience was found to correlate with WIT, operative time, and
blood loss. Overall 18.5% of patients developed complications. Complication rate
reduced with increasing surgeon experience. LC was 44 cases for WIT <=20 min, 44
cases for operative time <120 min, and 54 cases for blood loss <100 ml. Trifecta
outcome was achieved in 67.6% patients overall and was found to correlate with
increasing surgeon experience. Improvement in trifecta outcomes continued to
occur beyond the LC. Conclusions: RAPN is a viable option for nephron-sparing
surgery in patients with renal carcinoma. For a surgeon trained in laparoscopy,
acceptable perioperative outcomes following RAPN can be achieved after an LC of
about 44 cases. Increasing surgeon experience was associated with improved
"trifecta" achievement following RAPN.
PMID- 29343916
TI - Effects of tumor size and location on survival in upper tract urothelial
carcinoma after nephroureterectomy.
AB - Introduction: Upper Tract Urothelial Carcinoma (UTUC) is a rare disease with few
prognostic determinants. We sought to evaluate the impact of tumor size and
location on patient survival following nephroureterectomy for UTUC. Materials and
Methods: Data on 8284 patients treated with radical nephroureterectomy for UTUC
in the United States between 1998 and 2011 were analyzed from the National Cancer
Data Base. Univariable survivorship curves were generated based on pT stage, pN
stage, grade, tumor size, and tumor site (renal pelvis vs. ureter). A Cox
proportional hazards model was used to evaluate the effect of age, comorbidity, T
stage, lymph node involvement, tumor site, and tumor size on survival. Results:
The median follow-up time was 46 months. A majority of the patients were male
(55.4%) with a tumor size of >=3.5 cm (52.0%) and pT stage =3.5 cm the 5-year OS was 45.9% and
58.5%, respectively. On multivariable analysis controlling for age, Charlson
comorbidity index, grade, and tumor stage, tumor size >=3.5 cm was independently
predictive of worse OS (odds ratio: 1.13 [95% confidence interval: 1.02-1.26], P
= 0.023). Conclusions: Using the largest series of patients with UTUC undergoing
nephroureterectomy, we demonstrated a worse survival in patients with larger
tumor sizes (>=3.5 cm) but no difference in survival based on tumor location
while controlling for other pathologic characteristics. Incorporation of tumor
size into perioperative risk modeling may help with patient stratification and
provide further prognostic information for patient counseling.
PMID- 29343917
TI - Editorial comment on "Effects of tumor size and location on survival in upper
tract urothelial carcinoma after nephroureterectomy".
PMID- 29343918
TI - Pediatric pelvic fracture urethral distraction defect causing complete
urethrovaginal avulsion.
AB - Pelvic fracture with urethral injury in girls is an uncommon entity that is
usually associated with concomitant vaginal lacerations. Management options vary
from immediate exploration and urethral anastomosis to delayed urethroplasty. We
report our experience of managing a 10-year old girl presenting 6 months after a
pelvic fracture with urethrovaginal injury and a completely obliterated urethral
meatus managed successfully with a single-stage bladder tube repair.
PMID- 29343919
TI - Papillary renal cell carcinoma with abscess formation: A report of three cases.
AB - We report three cases of renal cell carcinoma (RCC) associated with abscess
formation. Such association has been reported uncommonly in literature. Our cases
were unique in that final histopathological report was papillary RCC in all of
the patients.
PMID- 29343920
TI - Extrarenal retroperitoneal angiomyolipoma with oncocytoma.
AB - The simultaneous presence of renal angiomyolipoma and oncocytoma is a rare
occurrence. Extrarenal retroperitoneal angiomyolipoma is an even more rare
neoplasm, and its simultaneous presence with renal oncocytoma has not been
documented. We present herein the first case to be reported in English
literature.
PMID- 29343921
TI - Ureteropelvic junction obstruction - mimicking an "elephant head" on magnetic
resonance imaging.
AB - Ureteropelvic junction obstruction (UPJO) with giant hydronephrosis is relatively
rare in adults as compared to children. Most of the UPJO reported or seen in
daily practice have a distinct hydronephrosis with a narrow ureteropelvic
junction and a collapsed ureter distally. We present images a case of an adult
female with Left UPJO, which on MRI mimicked an 'elephant head'.
PMID- 29343922
TI - Periureteral inferior vena caval venous ring presenting as urinary obstruction.
AB - The embryological development of the inferior vena cava (IVC) is complex, and
thus the vena cava may undergo a large number of congenital anomalies.
Periureteric venous ring is a rare developmental anomaly of IVC where the right
ureter passes through a slit-like opening in a partially duplicated infrarenal
IVC, resulting in dilatation of upper urinary tract. Split-bolus multidetector
computed tomography technique is useful in detecting such vascular anomaly
causing ureteric obstruction as it can clearly show the vascular and ureteric
phase in a single acquisition.
PMID- 29343923
TI - Author Reply Re: Goel A. Research training during residency. Indian J Urol
2017;33:257-8.
PMID- 29343924
TI - IJU Awards 2017.
PMID- 29343925
TI - From Editor's Desk.
PMID- 29343926
TI - Cancer: Prevention and Rehabilitation through Yoga.
PMID- 29343928
TI - Exploration of Lower Frequency EEG Dynamics and Cortical Alpha Asymmetry in Long
term Rajyoga Meditators.
AB - Background: Rajyoga meditation is taught by Prajapita Brahmakumaris World
Spiritual University (Brahmakumaris) and has been followed by more than one
million followers across the globe. However, rare studies were conducted on
physiological aspects of rajyoga meditation using electroencephalography (EEG).
Band power and cortical asymmetry were not studied with Rajyoga meditators. Aims:
This study aims to investigate the effect of regular meditation practice on EEG
brain dynamics in low-frequency bands of long-term Rajyoga meditators. Settings
and Design: Subjects were matched for age in both groups. Lower frequency EEG
bands were analyzed in resting and during meditation. Materials and Methods:
Twenty-one male long-term meditators (LTMs) and same number of controls were
selected to participate in study as par inclusion criteria. Semi high-density EEG
was recorded before and during meditation in LTM group and resting in control
group. The main outcome of the study was spectral power of alpha and theta bands
and cortical (hemispherical) asymmetry calculated using band power. Statistical
Analysis: One-way ANOVA was performed to find the significant difference between
EEG spectral properties of groups. Pearson's Chi-square test was used to find
difference among demographics data. Results: Results reveal high-band power in
alpha and theta spectra in meditators. Cortical asymmetry calculated through EEG
power was also found to be high in frontal as well as parietal channels. However,
no correlation was seen between the experience of meditation (years, hours)
practice and EEG indices. Conclusion: Overall findings indicate contribution of
smaller frequencies (alpha and theta) while maintaining meditative experience.
This suggests a positive impact of meditation on frontal and parietal areas of
brain, involved in the processes of regulation of selective and sustained
attention as well as provide evidence about their involvement in emotion and
cognitive processing.
PMID- 29343929
TI - Yoga Offers Cardiovascular Protection in Early Postmenopausal Women.
AB - Context: Postmenopause, an estrogen deficient state comes with increased
incidence of cardiovascular diseases (CVDs). Yoga has been described as having a
beneficial effect on heart rate variability (HRV), a marker for cardiac autonomic
activity which can assess cardiovascular risk, in various populations. Aim: the
aim of the study was to study the effect of 3-month long Yoga practice on HRV in
early postmenopausal women. Settings and Design: A prospective longitudinal study
of 67 women within 5 years of menopause between 45 and 60 years of age attending
menopause clinic of Department of Gynaecology, Sucheta Kriplani Hospital
fulfilling inclusion and exclusion criteria and consenting were enrolled for the
study. Subjects and Methods: HRV of 37 cases (Yoga group) and 30 controls (non
Yoga group) was recorded pre and 3-month postintervention. Statistical Analysis
Used: GraphPad Prism Version 5 software was used. Values are a mean and standard
error of mean. Statistical significance was set up at P < 0.05. Results: In HRV,
frequency domain analysis showed a significant fall in low frequency (LF) in
normalized units (nu) and LF: high frequency (HF) ratio and significant rise in
HF in nu in the Yoga group (depicting parasympathetic dominance) against a
significant rise in LF (nu) and LF: HF ratio and significant fall in HF (nu) in
non-Yoga group (indicating sympathetic dominance). Time domain analysis showed a
significant decrease in Standard Deviation of NN intervals in Non-Yoga group
against nonsignificant changes in Yoga group indicating deterioration in
parasympathetic activity in non-Yoga group. Conclusions: Three-month long Yoga
practice improved HRV in early postmenopausal women significantly and has the
potential to attenuate the CVD risk in postmenopausal women.
PMID- 29343927
TI - Yoga into Cancer Care: A Review of the Evidence-based Research.
AB - To cope with cancer and its treatment-related side effects and toxicities, people
are increasingly using complementary and alternative medicine (CAM).
Consequently, integrative oncology, which combines conventional therapies and
evidence-based CAM practices, is an emerging discipline in cancer care. The use
of yoga as a CAM is proving to be beneficial and increasingly gaining popularity.
An electronic database search (PubMed), through December 15, 2016, revealed 138
relevant clinical trials (single-armed, nonrandomized, and randomized controlled
trials) on the use of yoga in cancer patients. A total of 10,660 cancer patients
from 20 countries were recruited in these studies. Regardless of some
methodological deficiencies, most of the studies reported that yoga improved the
physical and psychological symptoms, quality of life, and markers of immunity of
the patients, providing a strong support for yoga's integration into conventional
cancer care. This review article presents the published clinical research on the
prevalence of yoga's use in cancer patients so that oncologists, researchers, and
the patients are aware of the evidence supporting the use of this relatively safe
modality in cancer care.
PMID- 29343931
TI - Effect of Modified Slow Breathing Exercise on Perceived Stress and Basal
Cardiovascular Parameters.
AB - Context: Different types of breathing exercises have varied effects on
cardiovascular parameters and the stress levels in an individual. Aim: The aim of
this study was to assess the effect of a modified form of isolated alternate
nostril, slow breathing exercise on perceived stress, and cardiovascular
parameters in young, male volunteers. Settings and Design: This was a randomized
control study carried out at Advanced Centre for Yoga Therapy Education and
Research, Department of Physiology, Jawaharlal Institute of Postgraduate Medical
Education and Research, Puducherry in 2014. Subjects and Methods: Hundred healthy
male volunteers were randomized into control group, n = 50 and slow breathing
group (study), n = 50. Slow breathing exercise training was given to study group
for 30 min a day, 5 times/week for 12 weeks, under the supervision of certified
yoga trainers. Perceived Stress Scale (PSS) using Cohen's questionnaire,
anthropometric parameters such as body mass index (BMI), waist-hip ratio (WHR),
and cardiovascular parameters such as heart rate (HR), systolic blood pressure
(SBP), and diastolic blood pressure (DBP) were recorded at baseline and after 12
weeks. The control group did not receive any intervention. Slow breathing
exercise training was provided for the study group. During the study period, one
volunteer opted out of the study group due to personal reasons. Results: HR, SBP,
DBP, and PSS decreased significantly (P < 0.05) in the study group following 12
weeks slow breathing exercise training, while no significant change (P > 0.05)
was observed in BMI and WHR. There was no significant change in the control
group. Conclusion: Twelve weeks of modified slow breathing exercise reduced
perceived stress and improved the cardiovascular parameters. The above results
indicate that our modified slow breathing exercise is effective in reducing
stress and improving the cardiovascular parameters.
PMID- 29343930
TI - Yoga-Based Postoperative Cardiac Rehabilitation Program for Improving Quality of
Life and Stress Levels: Fifth-Year Follow-up through a Randomized Controlled
Trial.
AB - Objectives: This study was aimed to assess the efficacy of yoga-based lifestyle
program (YLSP) in improving quality of life (QOL) and stress levels in patients
after 5 years of coronary artery bypass graft (CABG). Methodology: Three hundred
patients posted for elective CABG in Narayana Hrudayalaya Super Speciality
Hospital, Bengaluru, were randomized into two groups: YLSP and conventional
lifestyle program (CLSP), and follow-up was done for 5 years. Intervention: In
YLSP group, all practices of integrative approach of yoga therapy such as yama,
niyama, asana, pranayama, and meditation were used as an add-on to conventional
cardiac rehabilitation. The control group (CLSP) continued conventional cardiac
rehabilitation only. Outcome Measures: World Health Organization (WHO)-QOL BREF
Questionnaire, Perceived Stress Scale, Positive and Negative Affect Scale
(PANAS), and Hospital Anxiety and Depression Scale (HADS) were assessed before
surgery and at the end of the 5th year after CABG. As data were not normally
distributed, Mann-Whitney U-test was used for between-group comparisons and
Wilcoxon's signed-rank test was used for within-group comparisons. Results: At
the end of 5 years, mental health (P = 0.05), perceived stress (P = 0.01), and
negative affect (NA) (P = 0.05) have shown significant improvements. WHO-QOL BREF
score has shown improvements in physical health (P = 0.046), environmental health
(P = 0.04), perceived stress (P = 0.001), and NA (P = 0.02) in YLSP than CLSP.
Positive affect has significantly improved in CLSP than YLSP. Other domains of
WHO-QOL-BREF, PANAS, and HADS did not reveal any significant between-group
differences. Conclusion: Addition of long-term YLSP to conventional cardiac
rehabilitation brings better improvements in QOL and reduction in stress levels
at the end of 5 years after CABG.
PMID- 29343932
TI - Effects of Multimodal Mandala Yoga on Social and Emotional Skills for Youth with
Autism Spectrum Disorder: An Exploratory Study.
AB - Context: Youth with autism spectrum disorder (ASD) demonstrates impairment in the
ability to socially and emotionally relate to others that can limit participation
in groups, interaction with peers, and building successful life relationships.
Aims: The aim of this exploratory study was to examine the effects of a novel
multimodal Mandala yoga program on social and emotional skills for youth with
ASD. Subjects and Methods: Five males with ASD attended 1 h yoga sessions, twice
a week for 4 weeks. Multimodal Mandala yoga comprised 26 circular partner/group
poses, color and tracing sheets, rhythmic chanting, yoga cards, and games.
Treatment and Research Institute for ASD Social Skills Assessment (TSSA) scores
were collected before and after the eight yoga sessions. The Modified Facial Mood
Scale (MFMS) was used to observe mood changes before and after each yoga class.
Paired sample t-tests were conducted on TSSA and MFMS scores to compare social
and emotional differences post the 4-week camp. Narrative field notes were
documented after each of the eight yoga sessions. Results: A significant
improvement from pre- to post-test was found in overall TSSA (t(4) = -5.744, P =
0.005) and on respondent to initiation (t(4) = -3.726, P = 0.020), initiating
interaction (t(4) = -8.5, P = 0.039), and affective understanding and perspective
taking subscales (t(4) = -5.171 P = 0.007). Youth's MFMS scores increased from
80% to 100% at the end of eight yoga sessions demonstrating a pleasant or
positive mood. Thematic analysis of the narrative notes identified three key
factors associated with the yoga experience: (a) enhanced mood and emotional
expression, (b) increased empathy toward others, and (c) improved teamwork
skills. Conclusion: This multimodal Mandala yoga training has implication for
developing positive social and emotional skills for youth with ASD.
PMID- 29343933
TI - Effects of Maharishi Yoga Asanas on Mood States, Happiness, and Experiences
during Meditation.
AB - Context/Background: Many studies showed positive effects of Yoga Asanas. There is
no study on Maharishi Yoga Asanas yet. This research replicated and expanded
observed improvements on the profile of mood states (POMS) as a result of 2-week
Maharishi Yoga Asanas course. Thirteen college students taking part in a 4-week
course on Maharishi Yoga Asanas were matched with 13 students taking other
courses at the university. Aims and Objective: The main objective of the study
was to assess the effects of Maharishi Yoga Asanas on mood states, degree of
happiness, and experiences in Transcendental Meditation (TM) practice. Methods:
All students were given two psychological tests and additional question before
and after their 4-week course: POMS, Meditation Depth Questionnaire, and question
about the degree of happiness. Results: Repeated measure MANOVA showed the 4-week
Maharishi Yoga Asanas course resulted in significant increase in happiness during
the day and significant improvements in (1) sense of personal self, (2)
transpersonal qualities, and (3) transpersonal self during their TM practice.
Conclusion: This research shows that Maharishi Yoga Asanas affect more than body
and mind. Rather they influence much deeper levels of one's subjectivity
including one's transpersonal self.
PMID- 29343934
TI - A Comparative Study on the Effects of Vintage Nonpharmacological Techniques in
Reducing Myopia (Bates eye exercise therapy vs. Trataka Yoga Kriya).
AB - Background: Human eye captures light rays as they come and fall on the retina and
convert them into an image. However, in myopia, light rays fall in front of
retina, causing blurring of image. Correction of this is generally done using
correcting devices such as corrective glasses and contact lenses. Existence of
some alternative therapies is also noticed in literature. Aim: To compare the
effects of Bates eye exercises and Trataka Yoga Kriya on myopia. Materials and
Methodology: Ethical clearance was obtained from the institution, and informed
consent was taken from participants. In this randomized comparative study, 24
participants (48 eyes) were taken based on inclusion and exclusion criteria and
were randomly divided into two groups: Group A and Group B, where Bates eye
exercise therapy and Trataka Yoga Kriya were given, respectively, for 8 weeks.
Participants were assessed for their refractive errors and visual acuity pre- and
post-intervention. Results: Data were analyzed by SPSS version 20. Results
obtained revealed that both Bates exercises and Trataka Yoga Kriya were not
significantly effective in reducing refractive errors and in improving visual
acuity (P value of refractive error in right eye: 0.4250; left eye: 0.4596; P
value of visual acuity in right eye: 0.5691; left eye: 0.8952). Conclusion: This
study concludes that nonpharmacological approaches such as eye exercises and
Trataka Yoga Kriya are not significant on myopia.
PMID- 29343935
TI - Effectiveness of Mindfulness-based Cognitive Therapy in Patients with Bipolar
Affective Disorder: A Case Series.
AB - The present investigation was undertaken to examine the effects of mindfulness
based cognitive therapy (MBCT) on interepisodic symptoms, emotional regulation,
and quality of life in patients with bipolar affective disorder (BPAD) in
remission. The sample for the study comprised a total of five patients with the
diagnosis of BPAD in partial or complete remission. Each patient was screened to
fit the inclusion and exclusion criteria and later assessed on the Beck
Depressive Inventory I, Beck Anxiety Inventory, Difficulties in Emotion
Regulation Scale, Acceptance and Action Questionnaire-II, and The World Health
Organization Quality of Life Assessment-BREF. Following preassessments, patients
underwent 8-10 weeks of MBCT. A single case design with pre- and post
intervention assessment was adopted to evaluate the changes. Improvement was
observed in all five cases on the outcome variables. The details of the results
are discussed in the context of the available literature. Implications,
limitations, and ideas for future investigations are also discussed.
PMID- 29343936
TI - The Conclusions Are Unsupported by the Data, Are Based on Invalid Analyses, Are
Incorrect, and Should be Corrected: Letter Regarding "Sleep Quality and Body
Composition Variations in Obese Male Adults after 14 weeks of Yoga Intervention:
A Randomized Controlled Trial".
PMID- 29343937
TI - Response to Comment on "Sleep Quality and Body Composition Variations in Obese
Male Adults after 14 Weeks of Yoga Intervention: A Randomized Controlled Trial"
by Rshikesan et al., 2017.
PMID- 29343938
TI - CINdex: A Bioconductor Package for Analysis of Chromosome Instability in DNA Copy
Number Data.
AB - The CINdex Bioconductor package addresses an important area of high-throughput
genomic analysis. It calculates the chromosome instability (CIN) index, a novel
measurement that quantitatively characterizes genome-wide copy number alterations
(CNAs) as a measure of CIN. The advantage of this package is an ability to
compare CIN index values between several groups for patients (case and control
groups), which is a typical use case in translational research. The
differentially changed cytobands or chromosomes can then be linked to genes
located in the affected genomic regions, as well as pathways. This enables in
depth systems biology-based network analysis and assessment of the impact of CNA
on various biological processes or clinical outcomes. This package was
successfully applied to analysis of DNA copy number data in colorectal cancer as
a part of multi-omics integrative study as well as for analysis of several other
cancer types. The source code, along with an end-to-end tutorial, and example
data are freely available in Bioconductor at
http://bioconductor.org/packages/CINdex/.
PMID- 29343939
TI - Kinetics of Procalcitonin in Pediatric Patients on Extracorporeal Membrane
Oxygenation.
AB - Objectives: To assess the kinetics of procalcitonin (PCT) and C-reactive protein
(CRP) in pediatric patients who required extracorporeal membrane oxygenation
(ECMO) and to analyze its relationship with morbidity and mortality. Patients and
methods: Prospective observational study including pediatric patients who
required ECMO. Both PCT and CRP were sequentially drawn before ECMO (P0) and
until 72 hours after ECMO. Results: A total of 40 patients were recruited. Two
cohorts were established based on the value of the P0 PCT (>10 ng/mL). Comparing
the kinetics of PCT and CRP in these cohorts, the described curves were the
expected for each clinical situation. The cutoff for P0 PCT to predict multiple
organ dysfunction syndrome was 2.55 ng/mL (sensibility 83%, specificity 100%).
Both PCT and CRP did not predict risk of neurologic sequelae or mortality in any
group. Conclusions: Procalcitonin does not seem to be modified by ECMO and could
be a good biomarker of evolution.
PMID- 29343940
TI - Prescreening whole exome sequencing results from patients with retinal
degeneration for variants in genes associated with retinal degeneration.
AB - Background: Accurate clinical diagnosis and prognosis of retinal degeneration can
be aided by the identification of the disease-causing genetic variant. It can
confirm the clinical diagnosis as well as inform the clinician of the risk for
potential involvement of other organs such as kidneys. It also aids in genetic
counseling for affected individuals who want to have a child. Finally, knowledge
of disease-causing variants informs laboratory investigators involved in
translational research. With the advent of next-generation sequencing,
identifying pathogenic mutations is becoming easier, especially the
identification of novel pathogenic variants. Methods: We used whole exome
sequencing on a cohort of 69 patients with various forms of retinal degeneration
and in whom screens for previously identified disease-causing variants had been
inconclusive. All potential pathogenic variants were verified by Sanger
sequencing and, when possible, segregation analysis of immediate relatives.
Potential variants were identified by using a semi-masked approach in which rare
variants in candidate genes were identified without knowledge of the clinical
diagnosis (beyond "retinal degeneration") or inheritance pattern. After the
initial list of genes was prioritized, genetic diagnosis and inheritance pattern
were taken into account. Results: We identified the likely pathogenic variants in
64% of the subjects. Seven percent had a single heterozygous mutation identified
that would cause recessive disease and 13% had no obviously pathogenic variants
and no family members available to perform segregation analysis. Eleven subjects
are good candidates for novel gene discovery. Two de novo mutations were
identified that resulted in dominant retinal degeneration. Conclusion: Whole
exome sequencing allows for thorough genetic analysis of candidate genes as well
as novel gene discovery. It allows for an unbiased analysis of genetic variants
to reduce the chance that the pathogenic mutation will be missed due to
incomplete or inaccurate family history or analysis at the early stage of a
syndromic form of retinal degeneration.
PMID- 29343941
TI - Clinical features of hypophosphatemic osteomalacia induced by long-term low-dose
adefovir dipivoxil.
AB - Objective: To investigate the predictors of hypophosphatemic osteomalacia induced
by adefovir dipivoxil (ADV) and to monitor for early detection. Patients and
methods: Hospitalized patients who were diagnosed with ADV-related hypo
phosphatemic osteomalacia were recruited and retrospectively analyzed in our
hospital from January 2012 to December 2016. A telephone interview was conducted
at 1, 3, 6, 9, 12, and 24 months after cessation of ADV. Results: In the 8
patients enrolled in the study, the hypophosphatemic osteomalacia symptoms
developed at an average of 5.14 (4-7) years since ADV treatment (10 mg/d). The
average alkaline phosphatase (ALP) level was 279.50 (137-548) U/L, which was
significantly higher than the normal level (45-125 U/L). The serum phosphorus
level was an average of 0.59 (0.43-0.69) mmol/L, which was lower than the normal
range (2.06-2.60 mmol/L). Serum calcium levels of the enrolled patients remained
within normal limits. Reduced estimated glomerular filtration rate (eGFR <29
mL/min/1.73 m2) was seen in 4 cases. The clinical manifestations were mainly
progressive systemic bone and joint pain, frequent fractures, trouble in walking,
height reduction (4-6 cm), and so on. After cessation of ADV, symptoms like bone
pain resolved gradually. Serum phosphorus level restored to normal in 4.5 months
after the withdrawal of ADV. However, in 4 patients, renal function failed to
return to normal in 24 months. Conclusion: More attention should be paid to the
duration of ADV treatment. The level of serum phosphorus and ALP, as well as
renal function, should be monitored for early detection of potential adverse drug
reactions.
PMID- 29343942
TI - Portulaca oleracea L. alleviates liver injury in streptozotocin-induced diabetic
mice.
AB - Purslane is a widespread succulent herb that exhibits various pharmacological
effects. The purpose of this study was to evaluate the protective effect of
Portulaca oleracea L. (purslane) on streptozotocin-induced diabetes in mice. Oral
glucose-tolerance tests were carried out to assess blood glucose levels and body
weight and food intake were recorded. The biochemical parameters anti-aspartate
aminotransferase, alanine aminotransferase, insulin, triglycerides, total
cholesterol, IL-6, IL-1beta, and TNFalpha were also measured. The pathological
condition of liver tissues were examined by hematoxylin-eosin staining. Rho,
ROCK1, ROCK2, NFkappaBp65, p-NFkappaBp65, IkappaBalpha, and p-IkappaBalpha
expression in liver tissue were analyzed by Western blot. Purslane increased body
weight and decreased food intake. Purslane also significantly reduced
concentrations of glucose, anti-aspartate aminotransferase, alanine
aminotransferase, triglycerides, total cholesterol, IL-6, IL-1beta, and TNFalpha
in serum. Serum insulin was elevated with purslane treatment. In addition,
pathologic liver changes in diabetic mice were also alleviated by purslane.
Obtained data revealed that purslane restored the levels of Rho-NFkappaB
signaling-related proteins in comparison with those of diabetic mice. Above all,
it can be assumed that purslane might play a positive role in regulating
streptozotocin-induced liver injury through suppressing the Rho-NFkappaB pathway.
PMID- 29343943
TI - The oral bioavailability, excretion and cytochrome P450 inhibition properties of
epiberberine: an in vivo and in vitro evaluation.
AB - Epiberberine (EPI) is a novel and potentially effective therapeutic and
preventive agent for diabetes and cardiovascular disease. To evaluate its
potential value for drug development, a specific, sensitive and robust high
performance liquid chromatography-tandem mass spectrometry assay for the
determination of EPI in rat biological samples was established. This assay was
used to study the pharmacokinetics, bioavailability and excretion of EPI in rats
after oral administration. In addition, a cocktail method was used to compare the
inhibition characteristics of EPI on cytochrome P450 (CYP450) isoforms in human
liver microsomes (HLMs) and rat liver microsomes (RLMs). The results demonstrated
that EPI was rapidly absorbed and metabolized after oral administration (10, 54
or 81 mg/kg) in rats, with Tmax of 0.37-0.42 h and T1/2 of 0.49-2.73 h. The Cmax
and area under the curve values for EPI increased proportionally with the dose,
and the oral absolute bioavailability was 14.46%. EPI was excreted mainly in bile
and feces, and after its oral administration to rats, EPI was eliminated
predominantly by the kidneys. A comparison of the current half-maximal inhibitory
concentration and Ki values revealed that EPI demonstrated an obvious inhibitory
effect on CYP2C9 and CYP2D6. Furthermore, its effect was stronger in HLM than in
RLM, more likely to be a result of noncompetitive inhibition.
PMID- 29343944
TI - Quantitative assessment of the effects of chitosan intervention on blood pressure
control.
AB - Background: Chitosan is a popular dietary fiber often used to reduce dietary fat
absorption to control weight and blood lipids. However, its effects on blood
pressure (BP) have not been fully elucidated. We evaluated the effects of
chitosan administration on systolic blood pressure (SBP) and diastolic blood
pressure (DBP) through a pooled analysis of available randomized controlled
trials (RCTs). Materials and methods: Electronic searches were conducted in
Medline, Cochrane Library, Scopus, and EMBASE to identify relevant human placebo
control RCTs. Trials that reported BP changes from baseline to study endpoint in
patients receiving treatment of chitosan were included for analysis. Weighted
mean difference (WMD) and 95% CIs were pooled using fixed-effects or random
effects models. Statistical heterogeneity, prespecified subgroup, publication
bias, sensitivity analysis, and meta-regression assessments were also tested.
Results: Six hundred and seventeen participants from eight trials with 10 arms
were included. Overall, chitosan administration did not significantly lower SBP
(WMD: -1.41 mmHg, 95% CI: -3.29 to 0.47; P=0.14) and DBP (WMD: -0.61 mmHg, 95%
CI: -1.75 to 0.52; P=0.29). However, our subgroup analyses indicated that
chitosan consumption significantly reduced DBP in shorter-term (<12 weeks) and
higher-dose (>2.4 g/day) arms. Funnel plots or Egger's tests analysis (P=0.36 and
0.43 for SBP and DBP, respectively) demonstrated that there was no significant
publication bias in this study. Conclusion: This meta-analysis indicates that
chitosan consumption significantly decreases DBP at higher dosage and in shorter
term interventions, while chitosan has no significant effects on SBP. However,
these results should be interpreted cautiously because of the limited eligible
RCTs included in this meta-analysis; further large-scale, well-designed RCTs on
this topic are urgently needed.
PMID- 29343945
TI - The impact of pharmaceutical interventions on the rational use of proton pump
inhibitors in a Chinese hospital.
AB - Background: The prescriptions of proton pump inhibitors (PPIs) have raised
concern due to both huge increase in medical expenditure and the possible long
term adverse events caused by them; therefore, an approach to taper off the
irrational use of PPIs by patients is clinically warranted. The aim of this study
was to evaluate the impact of pharmaceutical interventions on the rational use of
PPIs. Patients and methods: A single-center, pre- to post-intervention study
(pharmaceutical interventions group and control group) was performed in a Chinese
hospital. Pharmaceutical interventions were performed in the post-intervention
group, including educative group activities, real-time monitoring of clinical
records and making recommendations to doctors on PPI prescriptions based on the
criteria set at the beginning of the study. The number of patients with rational
indication, the accuracy rate of administration route, the duration of therapy
and the changes in total PPI costs, mean PPI costs, mean total drug costs and
mean hospitalization costs were the main outcome measures. Results: A total of
285 patients were included in the study. After 6 months of interventions,
significant improvements in the number of patients with rational indication were
found (96.5% in the pharmaceutical interventions group vs 71.8% in the control
group, P<0.01). The accuracy rate of administration route was increased (99.3% vs
73.2%, P<0.05), while the duration of therapy was decreased (7.9+/-0.5 vs 14.3+/
0.8, P<0.01). Pharmaceutical interventions led to significant reductions in mean
PPIs costs, mean total drug costs and mean hospitalization costs (P<0.001).
Conclusion: This study provides important evidence on the beneficial effect of
pharmaceutical interventions on enhancing the rational use of PPIs and
substantial cost saving by increasing the number of patients with rational
indication and reducing the risk for long-term adverse events.
PMID- 29343946
TI - A new pen device for injection of recombinant human growth hormone: a
convenience, functionality and usability evaluation study.
AB - Purpose: Adherence to recombinant human growth hormone (r-hGH) is critical to
growth and other outcomes in patients with growth disorders, but the requirement
for daily injections means that ease of use is an important factor. This study
assessed the perceived ease of use and functionality of the prototype of a
reusable pen injector (pen device) for r-hGH that incorporates several advanced
features. Participants and methods: Semi-structured 60-minute qualitative
interviews were conducted in 5 countries with 57 health care professionals (HCPs)
and 30 patients with GH deficiency/caregivers administering r-hGH to patients,
including children. HCPs had to be responsible for training in the use of r-hGH
pen devices and to see >=4 r-hGH patients/caregivers per month.
Patients/caregivers had to have experience with r-hGH administration for at least
6 months. Results: Thirty-seven (65%) of HCPs described the pen device as
"simple" or "easy" to use. The aluminum body was generally perceived as
attractive, high quality and comfortable to hold and operate. The ease of
preparation and use made it suitable for both children and adults. The ability to
dial back the r-hGH dose, if entered incorrectly, was mentioned as a major
benefit, because other devices need several user steps to reset.
Patients/caregivers felt the pen device was easy to use and the injection
feedback features reassured them that the full dose had been given. Overall, 40
(70%) HCPs and 16 (52%) patients/caregivers were likely to recommend or request
the pen device. Moreover, patients/caregivers rated the pen device higher than
their current reusable pens and almost equal to the leading disposable device for
ease of learning, preparation, administration and ease of use. Conclusion: The
prototype pen device successfully met its design objectives and was very well
accepted by HCPs and patients/caregivers for its ease of use, appearance and
functionality.
PMID- 29343947
TI - Patient preferences for important attributes of bipolar depression treatments: a
discrete choice experiment.
AB - Purpose: The purpose of this study was to assess patient preferences regarding
pharmacological treatment attributes for bipolar depression using a discrete
choice experiment (DCE). Methods: Adult members of an Internet survey panel with
a self-reported diagnosis of bipolar depression were invited via e-mail to
participate in a web-based DCE survey. Participants were asked to choose between
hypothetical medication alternatives defined by attributes and levels that were
varied systematically. The six treatment attributes included in the DCE were time
to improvement, risk of becoming manic, weight gain, risk of sedation, increased
blood sugar, and increased cholesterol. Attributes were supported by literature
review, expert input, and results of focus groups with patients. Sawtooth CBC
System for Choice-Based Conjoint Analysis was used to estimate the part-worth
utilities for the DCE analyses. Results: The analytical sample included 185
participants (50.8% females) from a total of 200 participants. The DCE analyses
found weight gain to be the most important treatment attribute (relative
importance =49.6%), followed by risk of sedation (20.2%), risk of mania (13.0%),
increased blood sugar (8.3%), increased cholesterol (5.2%), and time to
improvement (3.7%). Conclusion: Results from this DCE suggest that adults with
bipolar depression considered risks of weight gain and sedation associated with
pharmacotherapy as the most important attributes for the treatment of bipolar
depression. Incorporating patient preferences in the treatment decision-making
process may potentially have an impact on treatment adherence and satisfaction
and, ultimately, patient outcomes.
PMID- 29343948
TI - Types and delivery of emotional support to promote linkage and engagement in HIV
care.
AB - Purpose: Despite recommendations for early entry into human immunodeficiency
virus (HIV) care, many people diagnosed with HIV delay seeking care. Multiple
types of social support (ie, cognitive, emotional, and tangible) are often needed
for someone to transition into HIV care, but a lack of emotional support at
diagnosis may be the reason why some people fail to stay engaged in care. Thus,
the purpose of this study was to identify how people living with HIV
conceptualized emotional support needs and delivery at diagnosis. Method: We
conducted a secondary analysis of qualitative data from 27 people living with
HIV, many of whom delayed entry into HIV care. Results: Participants described
their experiences seeking care after an HIV diagnosis and identified components
of emotional support that aided entry into care - identification, connection, and
navigational presence. Many participants stated that these types of support were
ideally delivered by peers with HIV. Conclusion: In clinical practice, providers
often use an HIV diagnosis as an opportunity to educate patients about HIV
prevention and access to services. However, this type of social support may not
facilitate engagement in care if emotional support needs are not met.
PMID- 29343949
TI - Clinical observations on the use of new anti-VEGF drug, conbercept, in age
related macular degeneration therapy: a meta-analysis.
AB - Purpose: Conbercept is a new anti-vascular endothelial growth factor (VEGF) drug
approved for the treatment of age-related macular degeneration (AMD). Although
this novel drug has been widely used in clinic, unlike other anti-VEGF drugs,
validation and consensus on its method of clinical application and clinical
safety have not yet been achieved. Methods: Relevant literature was searched on
PubMed, Web of Science, China National Knowledge Internet, and Wanfang Data.
Stata 12.0 was used for data analysis. Random- and fixed-effect models were
employed to evaluate heterogeneity. Best-corrected visual acuity (BCVA) and
central retinal thickness (CRT) were utilized to measure the improvement of AMD
patients. Results: In this study, we analyzed conbercept administration and
compared its application with other control clinical methods for AMD treatment.
Ranibizumab, triamcinolone, and traditional transpupillary thermotherapy (TTT)
were administered in the control group. No differences were found in the BCVA and
CRT improvement between the groups treated with conbercept and ranibizumab.
However, the conbercept group had a lower serum VEGF level. After 3 months of
treatment, conbercept led to a more significant BCVA and CRT improvement than
triamcinolone. A more considerable BCVA improvement was observed in the group
treated with conbercept than in the group treated with TTT. Moreover, even 6
months after the treatment, the effect of conbercept on CRT improvement was still
more pronounced than that of TTT. Conclusion: In AMD patients, conbercept exerts
considerably more positive effects on the long-term BCVA and CRT improvement than
triamcinolone and TTT. The serum VEGF level in the conbercept group was lower
than that in the ranibizumab group.
PMID- 29343950
TI - Examining 30-day COPD readmissions through the emergency department.
AB - Background: Thirty-day readmission in COPD is common and costly, but potentially
preventable. The emergency department (ED) may be a setting for COPD readmission
reduction efforts. Objective: To better understand COPD readmission through the
ED, ascertain factors associated with 30-day readmission through the ED, and
identify subgroups of patients with COPD for readmission reduction interventions.
Patients and methods: A retrospective cohort study was conducted from January
2009 to September 2015 in patients with COPD of age >=18 years. Electronic health
record data were abstracted for information available to admitting providers in
the ED. The primary outcome was readmission through the ED within 30 days of
discharge from an index admission for COPD. Logistic regression was used to
examine the relationship between potential risk factors and 30-day readmission.
Results: The study involved 1,574 patients who presented to the ED within 30 days
on an index admission for COPD. Of these, 82.2% were readmitted through the ED.
Charlson score (odds ratio [OR]: 3.6; 95% CI: 2.9-4.4), a chief complaint of
breathing difficulty (OR: 1.6; 95% CI: 1.1-2.6), outpatient utilization of
albuterol (OR: 4.1; 95% CI: 2.6-6.4), fluticasone/salmeterol (OR: 2.3; 95% CI:
1.3-4.2), inhaled steroids (OR: 3.8; 95% CI: 1.3-10.7), and tiotropium (OR: 1.8;
95% CI: 1.0-3.2), as well as arterial blood gas (OR: 4.4; 95% CI: 1.3-15.1) and B
type natriuretic peptide (OR: 2.2; 95% CI: 1.4-3.5) testing in the ED were
associated with readmission (c-statistic =0.936). Seventeen-point-eight percent
of patients with COPD presented to the ED and were discharged home; 56% presented
with a complaint other than breathing difficulty; and 16% of those readmitted for
breathing difficulty had a length of stay <48 hours. Conclusion: Intensive
outpatient monitoring, evaluation, and follow-up after discharge are needed to
help prevent re-presentation to the ED, as practically all patients with COPD who
represent to the ED within 30 days are readmitted to the hospital and for a
variety of clinical complaints. Among those patients with COPD who present with
breathing difficulty, improved decision support algorithms and alternative
management strategies are needed to identify and intervene on the subgroup of
patients who require <48-hour length of stay.
PMID- 29343951
TI - Risk factors predict frequent hospitalization in patients with acute exacerbation
of COPD.
AB - Purpose: COPD is a heterogeneous disease, and the available prognostic indexes
are therefore limited. This study aimed to identify the factors associated with
acute exacerbation leading to hospitalization. Patients and methods: This was a
retrospective study of consecutive patients with COPD (meeting the Global
Initiative for Chronic Obstructive Lung Disease [GOLD] diagnostic criteria)
hospitalized at the Ninth Hospital of Xi'an Affiliated Hospital of Xi'an Jiaotong
University between October 2014 and September 2016. During follow-up after first
hospitalization, the patients who had been rehospitalized within 1 year for acute
exacerbation were grouped into the frequent exacerbation (FE) group, while the
others were grouped into the infrequent exacerbation (IE) group. The baseline
demographic, clinical, laboratory, pulmonary function, and imaging data were
compared between the two groups. Results: Compared with the IE group, the FE
group had lower forced expiratory volume in 1 second (FEV1)/forced vital capacity
(FVC) (P=0.005), FEV1%pred (P=0.002), maximal mid-expiratory flow (MMEF25
75%pred) (P=0.003), and ratio of carbon monoxide diffusion capacity to alveolar
ventilation (DLCO/VA) (P=0.03) and higher resonant frequency (Fres; P=0.04).
According to generations of bronchi, the percentage of the wall area (%WA) of
lobes was found to be higher in the FE group. Emphysema index (EI), mean
emphysema density (MED)whole and MEDleft lung in the FE group were significantly
worse than in the IE group (P<0.05). Using logistic regression, exacerbation
hospitalizations in the past year (odds ratio [OR] 14.4, 95% CI 6.1-34.0,
P<0.001) and EI >10% (OR 2.9, 95% CI 1.2-7.1, P=0.02) were independently
associated with frequent acute exacerbation of COPD (AECOPD) hospitalization.
Conclusion: Exacerbation hospitalizations in the past year and imaging features
of emphysema (EI) were independently associated with FE hospitalization.
PMID- 29343952
TI - Understanding of COPD among final-year medical students.
AB - Objective: Several previous studies have shown a suboptimal level of
understanding of COPD among different population groups. Students in their final
year of Medicine constitute a population that has yet to be explored. The
evaluation of their understanding provides an opportunity to establish strategies
to improve teaching processes. The objective of the present study is to determine
the current level of understanding of COPD among said population. Methods: A
cross-sectional observational study was done using digital surveys given to
medical students in their final year at the Universidad de Sevilla. Those
surveyed were asked about demographic data, smoking habits as well as the
clinical manifestation, diagnosis and treatment of COPD. Results: Of the 338
students contacted, responses were collected from 211 of them (62.4%). Only 25.2%
had an accurate idea about the concept of the disease. The study found that 24.0%
of students were familiar with the three main symptoms of COPD. Tobacco use was
not considered a main risk factor for COPD by 1.5% of students. Of those
surveyed, 22.8% did not know how to spirometrically diagnose COPD. Inhaled
corticosteroids were believed to be part of the main treatment for this disease
among 51.0% of the students. Results show that 36.4% of respondents believed that
home oxygen therapy does not help COPD patients live longer. Only 15.0%
considered the Body-mass index, airflow Obstruction, Dyspnea, and Exercise (BODE)
index to be an important parameter for measuring the severity of COPD. Giving up
smoking was not believed to prevent worsening COPD among 3.4% of students
surveyed. Almost half of students (47.1%) did not recommend that those suffering
from COPD undertake exercise. Conclusion: The moderate level of understanding
among the population of medical students in their final year shows some strengths
and some shortcomings. Teaching intervention is required to reinforce solid
knowledge among this population.
PMID- 29343953
TI - Impact of acute exacerbations on platelet reactivity in chronic obstructive
pulmonary disease patients.
AB - Background: A higher risk of atherothrombotic cardiovascular events, which are
platelet-driven processes, has been described during acute exacerbations of
chronic obstructive pulmonary disease (AECOPD). However, the relevance of
platelet reactivity during AECOPD and whether this is affected by antiplatelet
agents are not fully elucidated to date. This study aimed to evaluate whether
platelet reactivity is augmented during an exacerbation in COPD patients with and
without antiplatelet therapy and its association with systemic inflammatory
parameters. Materials and methods: Prospective, observational, ex vivo
investigation was conducted in consecutive patients suffering an exacerbation of
COPD. Platelet reactivity was assessed during AECOPD and at stable state.
Platelet function assays included: 1) vasodilator-stimulated phosphoprotein assay
expressed as P2Y12 reactivity index (PRI), 2) multiple electrode aggregometry and
3) optical aggregometry. Systemic inflammatory parameters such as leukocyte
count, interleukin-6 and fibrinogen were also assessed. Results: Higher platelet
reactivity was observed during AECOPD compared to stability measured by
vasodilator-stimulated phosphoprotein (PRI: 75.2%+/-1.9% vs 68.8%+/-2.4%,
p=0.001). This augmented platelet aggregability was also observed in the subset
of patients on antiplatelet therapy (PRI: 72.8%+/-3.1% vs 61.7%+/-7.5%, p=0.071).
Consistent findings were observed with all other platelet function tests.
Patients with greater enhancement of inflammatory markers during AECOPD were more
likely to present a higher increase in platelet reactivity. Conclusion: Platelet
reactivity is increased during AECOPD, which may contribute to the augmented
cardiovascular risk of these patients. Additionally, the increase in platelet
reactivity might be associated with an increment in inflammatory markers during
exacerbations.
PMID- 29343954
TI - Exposure to environmental tobacco smoke from husband more strongly impacts on the
airway obstruction of nonsmoking women.
AB - Background: The impact of airway obstruction of nonsmoking women caused by their
husband's smoking is unclear, despite the association between environmental
tobacco smoke (ETS) exposure at home and obstructive pulmonary diseases among
nonsmoking women. The aim of this study was to provide evidence that ETS exposure
from the husband at home has a more significant influence on the airway
obstruction of nonsmoking women than other housemates. Participants and methods:
Nonsmoking women aged 40 years or older were recruited from the health checkup
during May 2015-December 2016, Japan. They answered structured questionnaires,
including ETS exposure from their husbands and other housemates (parents,
siblings and dependants), and performed spirometry. We categorized the women with
any history of ETS exposure from housemates into three groups (A = husband, B =
others and C = both of husband and others) and defined the control group as those
with no ETS exposure from housemates. Results: A total of 811 nonsmoking women
completed questionnaires and spirometry. The proportion of nonsmoking women who
had airway obstruction (forced expiratory volume in 1 second [FEV1]/forced vital
capacity [FVC] <70%) among Group A (7.5%) was significantly higher than those in
the control group (1.1%, p<0.01) and Group B (0.8%, p<0.01). The proportion of
airway obstruction in Group C (6.4%) was also higher than that in the control
group (p<0.05) and Group B (p<0.05). ETS exposure from husband (odds ratio [OR],
3.53; 95% confidence interval [CI], 1.48-8.42) remained strongly associated with
airway obstruction after multiple logistic regression analysis, adjusting for
age, housemate's smoking habits, family history and ETS exposure in childhood and
at work. Conclusion: Nonsmoking women who were exposed to ETS from their husband
had the lowest FEV1/FVC, and a higher proportion of them had airway obstruction
when compared to nonsmoking women who experienced ETS from housemates other than
their husbands. The findings suggest that tobacco control in husbands is the most
important measure to prevent airway obstruction of nonsmoking women at home.
PMID- 29343955
TI - Lysyl oxidase activates cancer stromal cells and promotes gastric cancer
progression: quantum dot-based identification of biomarkers in cancer stromal
cells.
AB - Purpose: Semiconductor quantum dots (QDs) are a promising alternative to organic
fluorescent dyes for multiplexed molecular imaging of cancer stroma, which have
great advantages in holistically analyzing the complex interactions among cancer
stromal components in situ. Patients and methods: A QD probe-based multiplexed
spectral molecular imaging method was established for simultaneous imaging. Three
tissue microarrays (TMAs) including 184 gastric cancer (GC) tissues were
constructed for the study. Multispectral analyses were performed for quantifying
stromal biomarkers, such as lysyl oxidase (LOX). The stromal status including
infiltrating of immune cells (high density of macrophages), angiogenesis (high
density of microvessel density [MVD], low neovessel maturation) and extracellular
matrix (ECM) remodeling (low density of type IV collagen, intense expression of
matrix metalloproteinase 9 [MMP-9]) was evaluated. Results: This study compared
the imaging features of the QD probe-based single molecular imaging method,
immunohistochemistry, and organic dye-based immunofluorescent methods, and showed
the advantages of the QD probe-based multiple molecular imaging method for
simultaneously visualizing complex components of cancer stroma. The risk of
macrophages in high density, high MVD, low neomicrovessel maturation, MMP-9
expression and low type IV collagen was significantly increased for the
expression of LOX. With the advantages of the established QD probe-based
multiplexed molecular imaging method, the spatial relationship between LOX and
stromal essential events could be simultaneously evaluated histologically.
Stromal activation was defined and then evaluated. Survival analysis showed that
the stromal activation was correlated with overall survival and disease-free
survival (P<0.001 for all). The expression of LOX was significantly increased in
the intense activation subgroup (P<0.001). Conclusion: Quantifying assessment of
the stroma indicates that the LOX may be a stromal marker for GC and stromal
activation, which is not only responsible for the ECM remodeling morphologically,
but also for the formation of invasive properties and recurrence. These results
support the possibility to integrate morphological and molecular biomarker
information for cancer research by the biomedical application of QDs.
PMID- 29343956
TI - Essential oil-loaded lipid nanoparticles for wound healing.
AB - Chronic wounds and severe burns are diseases responsible for severe morbidity and
even death. Wound repair is a crucial process and tissue regeneration enhancement
and infection prevention are key factors to minimize pain, discomfort, and scar
formation. The aim of this work was the development of lipid nanoparticles (solid
lipid nanoparticles and nanostructured lipid carriers [NLC]), to be loaded with
eucalyptus or rosemary essential oils and to be used, as medical devices, to
enhance healing of skin wounds. Lipid nanoparticles were based on natural lipids:
cocoa butter, as solid lipid, and olive oil or sesame oil, as liquid lipids.
Lecithin was chosen as surfactant to stabilize nanoparticles and to prevent their
aggregation. The systems were prepared by high shear homogenization followed by
ultrasound application. Nanoparticles were characterized for physical-chemical
properties, bioadhesion, cytocompatibility, in vitro proliferation enhancement,
and wound healing properties toward normal human dermal fibroblasts.
Antimicrobial activity of nanoparticles was evaluated against two reference
microbial strains, one of Staphylococcus aureus, the other of Streptococcus
pyogenes. Finally, the capability of nanoparticles to promote wound healing in
vivo was evaluated on a rat burn model. NLC based on olive oil and loaded with
eucalyptus oil showed appropriate physical-chemical properties, good bioadhesion,
cytocompatibility, in vitro proliferation enhancement, and wound healing
properties toward fibroblasts, associated to antimicrobial properties. Moreover,
the in vivo results evidenced the capability of these NLC to enhance the healing
process. Olive oil, which is characterized by a high content of oleic acid,
proved to exert a synergic effect with eucalyptus oil with respect to
antimicrobial activity and wound repair promotion.
PMID- 29343957
TI - Codelivery of doxorubicin and MDR1-siRNA by mesoporous silica nanoparticles
polymerpolyethylenimine to improve oral squamous carcinoma treatment.
AB - Oral cancer is a type of head and neck cancer that is the seventh most frequent
cancer and the ninth most frequent cause of death globally. About 90% of oral
cancer is of squamous cell carcinoma type. Surgery and radiation with and without
chemotherapy are the major treatments for oral cancer. Better advanced treatment
is still needed. Multidrug resistance plays an important role in failure of oral
cancer chemotherapy. In this study, we tried to fabricate a novel nanoparticle
that could carry both MDR1-siRNA to block MDR1 expression and doxorubicin (DOX),
a chemotherapy drug, into cancer cells in order to directly kill the cells with
little or no effect of multidrug resistance. Results showed that mesoporous
silica nanoparticles (MSNP) can be modified by cationic polymerpolyethylenimine
(PEI) to obtain positive charges on the surface, which could enable the MSNP to
carry MDR1-siRNA and DOX. The transfection efficiency assays demonstrated that
the MSNP-PEI-DOX/ MDR1-siRNA was efficiently transfected into KBV cells in vitro.
KBV cells transfected with MSNP-PEI-DOX/MDR1-siRNA could effectively decrease
gene expression of MDR1 (~70% increase after 72 hours posttreatment) and induce
the apoptosis of KBV cells (24.27% after 48 hours posttreatment) in vitro.
Importantly, MSNP-PEI-DOX/MDR1-siRNA dramatically reduced the tumor size (81.64%
decrease after 28 days posttreatment) and slowed down tumor growth rate compared
to the control group in vivo (P<0.05). In the aggregate, newly synthesized MSNP
PEI-DOX/MDR1-siRNA improves cancer chemotherapy effect in terms of treating
multidrug-resistant cancer compared to DOX only, clearly demonstrating that MSNP
PEI-DOX/MDR1-siRNA has potential therapeutic application for multidrug-resistant
cancer in the future.
PMID- 29343958
TI - Preparation of anastrozole loaded PEG-PLA nanoparticles: evaluation of apoptotic
response of breast cancer cell lines.
AB - Purpose: Anastrozole (ANS) is an aromatase inhibitor that is widely used as a
treatment for breast cancer in postmenopausal women. Despite the wide use of ANS,
it is associated with serious side effects due to uncontrolled delivery. In
addition, ANS exhibits low solubility and short plasma half-life. Nanotechnology
based drug delivery has the potential to enhance the efficacy of drugs and
overcome undesirable side effects. In this study, we aimed to prepare novel ANS
loaded PLA-PEG-PLA nanoparticles (ANS-NPs) and to compare the apoptotic response
of MCF-7 cell line to both ANS and ANS-loaded NPs. Method: ANS-NPs were
synthesized using double emulsion method and characterized using different
methods. The apoptotic response was evaluated by assessing cell viability,
morphology, and studying changes in the expression of MAPK3, MCL1, and c-MYC
apoptotic genes in MCF-7 cell lines. Results: ANS was successfully encapsulated
within PLA-PEG-PLA, forming monodisperse therapeutic NPs with an encapsulation
efficiency of 67%, particle size of 186+/-27.13, and a polydispersity index of
0.26+/-0.11 with a sustained release profile extended over 144 hours. In
addition, results for cell viability and for gene expression represent a similar
apoptotic response between the free ANS and ANS-NPs. Conclusion: The synthesized
ANS-NPs showed a similar therapeutic effect as the free ANS, which provides a
rationale to pursue pre-clinical evaluation of ANS-NPs on animal models.
PMID- 29343959
TI - Antitumor effect of a new nano-vector with miRNA-135a on malignant glioma.
AB - Introduction: MiR-135a is found to selectively induce apoptosis in glioma cell
but not in normal neurons and glial cells. However, low transfection efficacy
limits its application in vivo as other miRNAs. We prepared a new kind of nano
vector based on polyethylene glycol methyl ether (mPEG) and hyper-branched
polyethylenimine (hy-PEI) in order to improve the miRNA delivery system into the
glioma cells. Methods: The mPEG-g-PEI/miR-135a was constructed and detected by 1H
NMR and FTIR analyses. Transmission electron microscope was utilized for its
characteristics. Stability and release efficiency was assessed by
electrophoresis. Biocompatibility was observed and analyzed through co-culture
with astrocytes and malignant glioma cells (C6). Transfection rate was monitored
by laser confocal microscopy and flow cytometry. The antitumor effect of mPEG-g
PEI/miR-135a to C6 was confirmed in vivo by MR scanning, pathology and survival
curve. RT-PCR was used to assay transfection efficiency of mPEG-g-PEI/miR-135a in
vitro and in vivo. And Western blotting was used to assess the expressions of the
targeted proteins of miR-135a. Results: In this experiment, we found the optimal
N/P ratio of mPEG-g-PEI/miR-135a was about 6 judged by Zeta potential, particle
size and encapsulation ability. The stability of mPEG-g-PEI/miR-135a in serum and
the release efficiency in acid(pH=5.0) of mPEG-g-PEI/miR-135a were simulated the
environment in vivo and in tumor. The mPEG-g-PEI nano-vector was co-cultured with
malignant glioma cell C6 and normal astrocytes in vitro and showed good
biocompatibility evaluated by CCK8 assay. The cell experiments in vitro indicated
that mPEG-g-PEI could significantly improve miR-135a transfection by enhancing
uptake effect of both normal glial and glioma cells. Given the C6 implanted in
situ model, we discovered that the mPEG-g-PEI/miR-135a could obviously increase
the survival period and inhibit the growth of glioma confirmed by MRI and
histochemistry. In addition, the transfection efficiency of mPEG-g-PEI was better
than that of other transfection agents either in vitro or in vivo confirmed by RT
PCR. Moreover, the expressions of the targeted proteins of miR-135a were
consistent with the in vitro results. Conclusion: These results suggest that mPEG
g-PEI is expected to provide a new effective intracellular miRNA delivery system
with low toxicity for glioma therapy.
PMID- 29343961
TI - Receiver operating characteristic curve analysis of the Child Behavior Checklist
and Teacher's Report Form for assessing autism spectrum disorder in preschool
aged children.
AB - Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder
characterized by social, behavioral, and communication impairments with an
estimated prevalence of 1 in 68 school-aged children. There is a need for
objective and easily applicable instruments for early identification of autistic
children to enable initiation of early interventions during a very sensitive
period of brain development and, consequently, optimize prognosis. Here, we
tested the utility of the Child Behavior Checklist (CBCL) and the Caregiver
Teacher's Report Form (C-TRF) scales for assessing ASD in Brazil, where ASD
screening research is emergent. Subjects and methods: A total of 70 children (2-5
years old, both sexes) were enrolled, including an ASD group (n=39) and a non-ASD
control group (n=31). The preschool versions of the CBCL and C-TRF were applied.
The CBCL and C-TRF results were compared between the ASD and non-ASD control
groups with Mann-Whitney U tests and receiver operating characteristic analyses.
Results: The CBCL and C-TRF were found to have moderate accuracy for the
dimensions withdrawn and autism spectrum problems, and to correlate with each
other. Conclusion: The CBCL and C-TRF may aid in early ASD detection.
PMID- 29343960
TI - Changes of serum uric acid and total bilirubin in elderly patients with major
postischemic stroke depression.
AB - Background: This was a longitudinal study which investigated the relationship
between serum uric acid (SUA) and total bilirubin (Tbil) upon admission in
elderly stroke patients and the occurrence of postischemic stroke depression
(IPSD) at 3, 6, and 9 months of post-stroke follow-up. Subjects and methods: Data
were analyzed for 525 acute ischemic stroke patients. Beck Depression Inventory
(BDI) scores >17 and Diagnostic and Statistical Manual of Mental Disorders,
Fourth Edition (DSM-IV) were used separately to screen and diagnose IPSD at 3, 6,
and 9 months post-stroke. Once IPSD was diagnosed, follow-up activities were
terminated. Results: High levels of SUA (odds ratio [OR]=2.08, P<0.01) and Tbil
(OR=2.31, P<0.01) in the first 3 months post-stroke and low levels of SUA
(OR=2.05, P=0.03) and Tbil (OR=2.79, P<0.01) from 3 to 6 months post-stroke were
identified as risk factors for major IPSD. At 3 months, patients with SUA levels
>=406.5 MUmol/L (males with SUA levels of >=409.5 MUmol/L and females with SUA
levels >=385.5 MUmol/L) and Tbil levels >=23.65 MUmol/L were more likely to
develop major IPSD. At 6 months, both SUA (area under curve [AUC]=0.625, P=0.005,
cutoff =194.0 MUmol/L) and Tbil (AUC=0.681, P=0.004, cutoff =6.75 MUmol/L) had
minor diagnostic values (AUC<0.700), although SUA levels <=214.5 MUmol/L
(AUC=0.756, P=0.001) in female patients had a good diagnostic value (AUC=0.722,
P=0.006) for major IPSD. At 9 months, major IPSD showed no statistical
relationship with either SUA (chi2=2.33, P=0.13) or Tbil (chi2=0.41, P=0.84).
Conclusion: Higher levels of SUA and Tbil on admission were closely related to
the occurrence of major IPSD within 3 months of stroke. Lower levels of these two
biomarkers on admission were characteristic for the occurrence of major IPSD
between 3 and 6 months post-stroke, while 6 months after stroke, there was no
relationship between major IPSD and these two biomarkers.
PMID- 29343962
TI - Functioning outcomes with adjunctive treatments for major depressive disorder: a
systematic review of randomized placebo-controlled studies.
AB - Objective: Patients with major depressive disorder (MDD) with inadequate response
to antidepressant treatment (ADT) may suffer a prolonged loss of functioning.
This review aimed to determine if self-rated functional measures are informative
in randomized placebo-controlled studies of adjunctive therapy in patients with
MDD and inadequate response to ADT. Methods: This was a systematic literature
review of articles in any language from the MEDLINE database published between
January 1990 and March 2017. Eligible studies met the following criteria:
patients with MDD; inadequate response to at least one ADT; adjunctive therapy
(pharmacological or otherwise) to ADT; placebo control group; randomized
controlled trial or a post hoc analysis of a randomized controlled trial;
reported a self-rated functioning scale. Study characteristics and functioning
efficacy data were extracted. Results: A total of 2,090 discrete records were
screened, 293 full-text articles were assessed for eligibility, and 26 studies
were included. All studies were acute (6-12 weeks) except for one 52-week study.
The only self-rated functioning scale used in the included studies was the
Sheehan Disability Scale (SDS). Of the 13 adjunctive agents identified,
aripiprazole, brexpiprazole, edivoxetine, and risperidone improved functioning
versus placebo (p<0.05), as measured by the SDS total or mean score. On the SDS
"work/studies" item, only aripiprazole had a statistically significant benefit,
in one study out of four. Thus, where a benefit was observed on the SDS total or
mean, this was generally driven by improvement on the "social life" and "family
life" items. A limitation of the review is that it only considered published
literature from one database. Conclusion: The SDS, a self-rated functional
measure, is informative in acute randomized placebo-controlled studies of
adjunctive therapy in patients with MDD and inadequate response to ADT. However,
the item that measures work performance may be less relevant to this population
than the items that measure social and family life.
PMID- 29343963
TI - Physical factors that influence patients' privacy perception toward a psychiatric
behavioral monitoring system: a qualitative study.
AB - Background: Psychiatric patients have privacy concerns when it comes to
technology intervention in the hospital setting. In this paper, we present
scenarios for psychiatric behavioral monitoring systems to be placed in
psychiatric wards to understand patients' perception regarding privacy.
Psychiatric behavioral monitoring refers to systems that are deemed useful in
measuring clinical outcomes, but little research has been done on how these
systems will impact patients' privacy. Methods: We conducted a case study in one
teaching hospital in Malaysia. We investigated the physical factors that
influence patients' perceived privacy with respect to a psychiatric monitoring
system. The eight physical factors identified from the information system
development privacy model, a comprehensive model for designing a privacy
sensitive information system, were adapted in this research. Scenario-based
interviews were conducted with 25 patients in a psychiatric ward for 3 months.
Results: Psychiatric patients were able to share how physical factors influence
their perception of privacy. Results show how patients responded to each of these
dimensions in the context of a psychiatric behavioral monitoring system.
Conclusion: Some subfactors under physical privacy are modified to reflect the
data obtained in the interviews. We were able to capture the different physical
factors that influence patient privacy.
PMID- 29343964
TI - Achalasia following reflux disease: coincidence, consequence, or accommodation?
An experience-based literature review.
AB - Achalasia is a motility disorder of the esophagus characterized by the defective
peristaltic activity of the esophageal body and impaired relaxation of the lower
esophageal sphincter due to the degeneration of the inhibitory neurons in the
myenteric plexus of the esophageal wall. The histopathological and
pathophysiological changes in achalasia have been well described. However, the
exact etiological factors leading to the disease still remain unclear. Currently,
achalasia is believed to be a multifactorial disease, involving both extrinsic
and intrinsic factors. Based on our experience and the review of literature, we
believe that gastroesophageal reflux disease (GERD) might be one of the
triggering factors leading to the development of achalasia. However, it is also
stated that the two diseases can simultaneously appear independently from each
other. Considering the large number and routine treatment of patients with GERD
and achalasia, the rare combination of the two may even remain unnoticed; thus,
the analysis of larger patient groups with this entity is not feasible. In this
context, we report four cases where long-standing reflux symptoms preceded the
development of achalasia. A literature review of the available data is also
given. We hypothesize that achalasia following the chronic acid exposure of the
esophagus is not accidental but either a consequence of a chronic inflammation or
a protective reaction of the organism in order to prevent aspiration and lessen
reflux-related symptoms. This hypothesis awaits further clinical confirmation.
PMID- 29343966
TI - Prevalence of antigliadin IgA antibodies in psoriasis vulgaris and response of
seropositive patients to a gluten-free diet.
AB - Introduction: The course of psoriasis relies on a variety of metabolic and
immunological parameters. Identification of underlying pro-inflammatory
conditions and their control is desired for optimal management. Background:
Increased prevalence of serum markers for celiac disease has been reported among
patients with psoriasis. The likelihood of occult celiac disease in a
subpopulation of patients has been postulated and gluten-free diets have been
reported to be effective. Patients and methods: The prevalence of gliadin IgA
antibodies was assessed among patients with psoriasis in an urban population. The
clinical effects of a strict gluten-free diet were followed. Results: Over a 2
year period, 97 patients with Psoriasis Area and Severity Index greater than 2.4
were recruited from a population followed in a dermatology clinic. Gliadin IgA
antibodies were assessed in all participants and in 91 controls. Elevated gliadin
IgA antibodies were found in 13 patients (14%) and two controls (2%). Values in
five patients were assessed as greater than 30.0 U/mL or "strong positive"
according to the manufacturer of the assay. All 13 patients were placed on a
strict gluten-free diet without any other modifications in their ongoing
treatment of psoriasis. Improvement of psoriatic lesions was observed in all
patients with positive gliadin IgA antibodies but the decline in the Psoriasis
Area and Severity Index score and the scaling down of pharmaceutical treatment
was more pronounced in the five patients with strong positive gliadin IgA
indicating an immune aberration amenable to diet changes. Conclusion: Prevalence
of antigliadin IgA antibody is significant among patients with psoriasis not
diagnosed with celiac disease or non-celiac gluten sensitivity. For all its
limitations, antigliadin IgA testing can identify patients likely to benefit from
gluten-free diets.
PMID- 29343965
TI - Postural tachycardia syndrome: current perspectives.
AB - Postural tachycardia syndrome (POTS) is the combination of an exaggerated heart
rate response to standing, in association with symptoms of lightheadedness or pre
syncope that improve when recumbent. The condition is often associated with
fatigue and brain fog, resulting in significant disruptions at a critical time of
diagnosis in adolescence and young adulthood. The heterogeneity of the underlying
pathophysiology and the variable response to therapeutic interventions make
management of this condition challenging for both patients and physicians alike.
Here, we aim to review the factors and mechanisms that may contribute to the
symptoms and signs of POTS and to present our perspectives on the clinical
approach toward the diagnosis and management of this complex syndrome.
PMID- 29343968
TI - SUN1 silencing inhibits cell growth through G0/G1 phase arrest in lung
adenocarcinoma [Retraction].
AB - [This retracts the article on p. 2825 in vol. 10, PMID: 28652764.].
PMID- 29343967
TI - Indoleamine 2,3-Dioxygenase Activity Increases NAD+ Production in IFN-gamma
Stimulated Human Primary Mononuclear Cells.
AB - IFN-gamma activation of mononuclear phagocytes significantly increases
indoleamine 2,3-dioxygenase (IDO) and flux through the kynurenine pathway (KP).
However, the effect of IDO on NAD+ synthesis, the end product of KP metabolism,
is unknown. To investigate this, primary human peripheral blood mononuclear cells
were cultured up to 10 days and activated with IFN-gamma in the presence or
absence of a poly(ADP-ribose) polymerase (PARP) inhibitor. Day 10 macrophages had
significantly higher NAD+ levels compared with monocytes. IFN-gamma activation of
macrophages resulted in the highest induction of IDO but decreased intracellular
NAD+ concentrations at both 24 and 48 hours. However, IFN-gamma activation of
both day 6 and day 10 macrophages in the presence of a PARP inhibitor resulted in
significantly higher intracellular NAD+ levels at 24 hours. This study provides
evidence for the first time that an immune-mediated increase in IDO activity
increases NAD+ biosynthesis concomitantly with an increase in NAD+ catabolism in
primary human macrophages.
PMID- 29343969
TI - The putative tumor suppressor, miR-199a, regulated by Snail, modulates clear cell
renal cell carcinoma aggressiveness by repressing ROCK1.
AB - Background: Aberrant expression of miR-199a has been frequently reported in
cancer studies; however, its role in renal cell carcinoma (RCC) has not been
examined in detail. Results: Here, we showed that miR-199a was downregulated in
RCC and associated with poor prognostic phenotype. Using luciferase and western
blot assays we identified that Rho-associated coiled coil-containing protein
kinases 1 (ROCK1) was a direct target gene for miR-199a. miR-199a regulated
proliferation, invasion, and apoptosis of clear cell renal cell carcinoma (ccRCC)
cells by modulating ROCK1 expression. Interestingly, we also found that miR-199a
was modulated by snail in ccRCC cells. Snail elevated ROCK1 expression by
repressing miR-199a activity. Conclusion: Altogether, our results identify a
crucial tumor suppressive role of miR-199a in the progression of ccRCC and
suggest that miR-199a might be an anticancer therapeutic target for ccRCC
patients.
PMID- 29343970
TI - A retrospective examination of the US Food and Drug Administration's clinical
pharmacology reviews of oncology biologics for potential use of therapeutic drug
monitoring.
AB - Background: Biologics have gained traction for use in oncology, but have
demonstrate clinical variability for efficacy and safety. Therapeutic drug
monitoring (TDM) can benefit patients' outcomes from a biologic therapy when the
latter has a defined therapeutic window. A clinically relevant therapeutic window
may exist for biologics with established exposure-response (E-R) relationships
for efficacy and/or safety and a documented maximum tolerated dose (MTD).
Additionally, the inter-individual variability (IIV) on the clearance (CL)
parameter could determine risks for patients falling outside the proposed
therapeutic window. Materials and methods: The US Food and Drug Administration
(FDA)-approved oncology biologics between 2005-2016 were reviewed via FDA "Purple
Book" (FDA-repository for licensed biologics). Data were extracted from
biologics' pharmacokinetic models available on the clinical pharmacology reviews
published on the FDA-Approved Drug Products website. Evaluated features for
biologics with established E-R relationships for efficacy and/or safety and MTD
include an IIV for the CL and various other covariates including demographic
factors, disease factors, blood chemistry, or immunogenicity. Results: Five
therapies were identified with documented E-R relationships for both efficacy and
safety including, Yervoy(r)(ipilimumab), Zaltrap(r) (ziv-aflibercept),
Portrazza(r) (necitumumab), Adcetris(r) (brentuximab-vedotin), and Blincyto(r)
(blinatumomab). The corresponding IIV on CL were: 34%, 33%, 29%, 47%, and 97%,
respectively. Among the five therapies, only three had defined MTD including,
brentuximab-vedotin, necitumumab, and blinatumomab. Conclusion: Of the
medications examined, blinatumomab was identified as the anticancer drug with the
most available information for the establishment of TDM, and hence, may benefit
through the use of TDM to optimize effectiveness and minimize patients' toxicity.
The approach used here may provide a generalizable framework to retrospectively
identify anticancer biologics with high IIV that may benefit from TDM to improve
patients' clinical outcome.
PMID- 29343971
TI - Assessment of the cardiac safety between cetuximab and panitumumab as single
therapy in Chinese chemotherapy-refractory mCRC.
AB - Objective: The cardiac safety of cetuximab and panitumumab, particularly as
single agents, has not been investigated extensively. This trial was designed to
specifically evaluate the cardiac safety of cetuximab and panitumumab as single
therapy in Chinese chemotherapy-refractory metastatic colorectal cancer (mCRC)
patients. Patients and methods: Sixty-one patients received cetuximab at an
initial dose of 400 mg/m2 intravenously over 120 minutes on day 1 (week 1),
followed by a maintenance dose of 250 mg/m2 intravenously over 60 minutes on day
1 of each 7-day cycle. Forty-three patients received panitumumab at a dose of 6
mg/kg intravenously every 14 days. Routine laboratory tests and electrocardiogram
(ECG) were performed at baseline, during therapy and after the treatment (4th and
10th months). The incidence of elevation of troponin I ultra (TNI Ultra),
abnormal ECGs, cardiac events and noncardiac adverse events (AEs) were recorded
and analyzed. Results: The incidence of elevation of TNI Ultra between the two
groups had no significance (p=0.681), and TNI Ultra+ was observed more frequently
in patients with metastases to more than three organs and they received fourth or
above lines of chemotherapy. The most frequent abnormal ECG manifestations were
nonspecific ST changes and QTc prolongation in the two groups. At 10 months after
treatment, most of the abnormal ECG manifestations were reversed. The most common
cardiac AEs of cetuximab and panitumumab included palpitations, dyspnea, chest
pain and arrhythmias requiring treatment. Most of the events were mild and
transient. The incidence of cardiac AEs had no significant difference between the
two groups. Rash was still the most common noncardiac AE in both groups.
Conclusion: Cetuximab and panitumumab showed favorable cardiac safety as single
agents for Chinese chemotherapy-refractory mCRC patients. But monitoring for
cardiac AEs is still necessary throughout the entire treatment process.
PMID- 29343973
TI - A patient with classic biphasic pulmonary blastoma harboring CD74-ROS1 fusion
responds to crizotinib.
AB - Pulmonary blastoma (PB) is a rare aggressive lung malignancy with a poor
prognosis. Surgical resection is the treatment of choice for localized disease,
and there are no standard treatment guidelines for metastatic PB. Due to its
rareness, its molecular profile has not been elucidated. We present the first
case of classic biphasic pulmonary blastoma (CBPB) with CD74-ROS1 rearrangement
in a 44-year-old Asian female with stage IV disease diagnosed using capture-based
ultra-deep targeted sequencing. It has been reported that ROS1 rearranged lung
adenocarcinoma and squamous cell carcinoma are sensitive to crizotinib, an
ALK/MET/ ROS1 multitargeted tyrosine kinase inhibitor. However, its efficacy has
not been reported in CBPB patients harboring ROS1 rearrangement. This CBPB
patient was given crizotinib and she achieved partial response after 1 month of
treatment. We report the first clinical evidence of efficacy shown by crizotinib
for targeting CD74-ROS1 fusion in CBPB.
PMID- 29343972
TI - Targeting histone methyltransferase and demethylase in acute myeloid leukemia
therapy.
AB - Acute myeloid leukemia (AML) is a clonal disorder of myeloid progenitors
characterized by the acquisition of chromosomal abnormalities, somatic mutations,
and epigenetic changes that determine a consistent degree of biological and
clinical heterogeneity. Advances in genomic technologies have increasingly shown
the complexity and heterogeneity of genetic and epigenetic alterations in AML.
Among the genetic alterations occurring in AML, frequent are the genetic
alterations at the level of various genes involved in the epigenetic control of
the DNA methylome and histone methylome. In fact, genes involved in DNA
demethylation (such as DNMT3A, TET2, IDH1, and IDH2) or histone methylation and
demethylation (EZH2, MLL, DOT1L) are frequently mutated in primary and secondary
AML. Furthermore, some histone demethylases, such as LSD1, are frequently
overexpressed in AML. These observations have strongly supported a major role of
dysregulated epigenetic regulatory processes in leukemia onset and development.
This conclusion was further supported by the observation that mutations in genes
encoding epigenetic modifiers, such as DMT3A, ASXL1, TET2, IDH1, and IDH2, are
usually acquired early and are present in the founding leukemic clone. These
observations have contributed to development of the idea that targeting
epigenetic abnormalities could represent a potentially promising strategy for the
development of innovative treatments of AML. In this review, we analyze those
proteins and their inhibitors that have already reached the first stages of
clinical trials in AML, namely the histone methyltransferase DOT1L, the
demethylase LSD1, and the MLL-interacting protein menin.
PMID- 29343974
TI - Identification of key pathways and genes in TP53 mutation acute myeloid leukemia:
evidence from bioinformatics analysis.
AB - Background: Tumor protein p53 (TP53) mutations are not only a risk factor in
acute myeloid leukemia (AML) but also a potential biomarker for individualized
treatment options. This study aimed to investigate potential pathways and genes
associated with TP53 mutations in adult de novo AML. Methods: An RNA sequencing
dataset of adult de novo AML was downloaded from The Cancer Genome Atlas
database. Differentially expressed genes (DEGs) were identified by edgeR of the R
platform. Key pathways and genes were identified using the following
bioinformatics tools: gene set enrichment analysis (GSEA), gene ontology (GO),
the Kyoto Encyclopedia of Genes and Genomes (KEGG), Search Tool for the Retrieval
of Interacting Genes/Proteins, and Molecular Complex Detection. Results: GSEA
suggested that TP53 mutations were significantly associated with cell
differentiation, proliferation, cell adhesion biological processes, and MAPK
pathway. In total, 1,287 genes were identified as DEGs. GO and KEGG analysis
suggested that upregulation of DEGs was significantly enriched in categories
associated with cell adhesion biological processes, Ras-associated protein 1,
PI3K-Akt pathway, and cell adhesion molecules. The top ten genes ranked by
degree, CDH1, BMP2, KDR, LEP, CASR, ITGA2B, APOE, MNX1, NMU, and TRH, were
identified as hub genes from the protein-protein interaction network. Survival
analysis suggested that patients with TP53 mutations had a significantly
increased risk of death, while the mRNA expression level in patients with TP53
mutation was similar to those carrying TP53 wild type. Conclusion: Our findings
have indicated that multiple genes and pathways may play a crucial role in TP53
mutation AML, offering candidate targets and strategies for TP53 mutation AML
individualized treatment.
PMID- 29343975
TI - Spotlight on midostaurin in the treatment of FLT3-mutated acute myeloid leukemia
and systemic mastocytosis: design, development, and potential place in therapy.
AB - The Fms-like tyrosine kinase-3 (FLT3; fetal liver kinase-2; human stem cell
tyrosine kinase-1; CD135) is a class III receptor tyrosine kinase that is
normally involved in regulating the proliferation, differentiation, and survival
of both hematopoietic cells and dendritic cells. Mutations leading it to be
constitutively activated make it an oncogenic driver in ~30% of acute myeloid
leukemia (AML) patients where it is associated with poor prognosis. The
prevalence of oncogenic FLT3 and the dependency on its constitutively activated
kinase activity for leukemia growth make this protein an attractive target for
therapeutic intervention. Of the numerous small molecule inhibitors under
clinical investigation for the treatment of oncogenic FLT3-positive AML, the N
benzoyl-staurosporine, midostaurin (CGP41251; PKC412; Rydapt(r); Novartis Pharma
AG, Basel, Switzerland), is the first to be approved by the US Food and Drug
Administration for the treatment, in combination with standard chemotherapy, of
newly diagnosed adult AML patients who harbor mutations in FLT3. Here, we
describe the early design of midostaurin, the preclinical discovery of its
activity against oncogenic FLT3, and its subsequent clinical development as a
therapeutic agent for FLT3 mutant-positive AML.
PMID- 29343976
TI - Epidemiology, associated burden, and current clinical practice for the diagnosis
and management of Alzheimer's disease in Japan.
AB - The burden of dementia in Japan is large and growing. With the world's fastest
aging population, it is estimated that one in five elderly people will be living
with dementia in Japan by 2025. The most common form of dementia is Alzheimer's
disease (AD), accounting for around two-thirds of dementia cases. A systematic
review was conducted to examine the epidemiology and associated burden of AD in
Japan and to identify how AD is diagnosed and managed in Japan. English and
Japanese language databases were searched for articles published between January
2000 and November 2015. Relevant Japanese sources, clinical practice guideline
registers, and reference lists were also searched. Systematic reviews and cohort
and case-control studies were eligible for inclusion, with a total of 60 studies
included. The most recent national survey conducted in six regions of Japan
reported the mean prevalence of dementia in people aged >=65 years to be 15.75%
(95% CI: 12.4, 22.2%), which is much higher than the previous estimated rate of
10% in 2010. AD was confirmed as the predominant type of dementia, accounting for
65.8% of all cases. Advancing age and low education were the most consistently
reported risk factors for AD dementia. Japanese guidelines for the management of
dementia were released in 2010 providing specific guidance for AD about clinical
signs, image findings, biochemical markers, and treatment approaches.
Pharmacotherapies and non-pharmacotherapies to relieve cognitive symptoms were
introduced, as were recommendations to achieve better patient care. No studies
reporting treatment patterns were identified. Due to population aging and growing
awareness of AD in Japan, health care expenditure and associated burden are
expected to soar. This review highlights the importance of early detection,
diagnosis, and treatment of AD as strategies to minimize the impact of AD on
society in Japan.
PMID- 29343977
TI - Cost-effectiveness analysis of six therapies for the treatment of lower urinary
tract symptoms due to benign prostatic hyperplasia.
AB - Objective: To conduct a cost-effectiveness analysis from payers' perspectives of
six treatments for lower urinary tract symptoms (LUTS) associated with benign
prostatic hyperplasia (BPH) and to examine positioning of these modalities in the
marketplace for the best use of health care funds and quality-of-life benefits
for patients. Methods: The economic analysis was conducted with a Markov model to
compare combination prescription drug therapy (ComboRx), minimally invasive
therapies (MITs) including convective radiofrequency (RF) water vapor thermal
therapy (Rezum(r)), conductive RF thermal therapy (Prostiva(r)), and prostatic
urethral lift (UroLift(r)), and invasive surgical procedures including
photovaporization of the prostate (Greenlight(r) PVP) and transurethral resection
of the prostate (TURP). Effects assessed with International Prostate Symptom
Score, adverse events, and re-treatment rates were estimated from medical
literature; treatments effects were modeled using a common baseline score.
Starting with each therapy, patients' transitions to more intensive therapies
when symptoms returned were simulated in 6-month cycles over 2 years. Incremental
cost-effectiveness ratios (ICERs) were calculated for pairs of treatments;
uncertainty in ICERs was estimated with probabilistic sensitivity analyses.
Results: ComboRx was least effective and provided one-third of the symptom relief
achieved with MITs. UroLift was similar in effectiveness to Prostiva and Rezum
but costs more than twice as much. The cheaper MITs were ~$900 more expensive
than the cost of ComboRx generic drugs over 2 years. TURP and PVP provided
slightly greater relief of LUTS than MITs at approximately twice the cost over 2
years; typically, they are reserved for treatment of more severe LUTS.
Conclusion: The analysis evaluated the costs and symptom relief of six treatment
options in the continuum of care from a common baseline of LUTS severity.
Identification of treatments for LUTS/BPH that demonstrate cost-effectiveness and
provide appreciable symptom relief is paramount as reimbursement for patient care
moves from volume-based services to value-based services.
PMID- 29343978
TI - Parietal scalp is another affected area in female pattern hair loss: an analysis
of hair density and hair diameter.
AB - Purpose: Female pattern hair loss (FPHL) is a common hair disease. However,
studies of the quantitative measurement of FPHL are still limited. The aim of
this study was to investigate the characteristics of hair density and hair
diameter in normal women and FPHL patients, and further correlate the
quantitative measurement with the clinical presentation of FPHL. Patients and
methods: An evaluation of 471 FPHL patients and 236 normal women was carried out
according to the Ludwig classification, and analysis was performed by using a com
puterized handheld USB camera with computer-assisted software. Various areas of
the scalp, including frontal, parietal, midscalp, and occipital, were analyzed
for hair density, non-vellus hair diameter, and percentage of miniaturized hair.
Results: The hair density in normal women was the highest and the lowest in the
midscalp and parietal areas, respectively. The FPHL group revealed the lowest
hair density in the parietal area. Significant differences in hair density, non
vellus hair diameter, and percentage of miniaturized hair between the normal and
FPHL groups were observed, especially in the midscalp and parietal areas.
Conclusion: The parietal area is another important affected area in FPHL in
addition to the midscalp area. This finding provides novel important information
of FPHL and will be useful for hair transplant surgeons choosing the optimal
donor sites for hair transplantation in women.
PMID- 29343979
TI - The influence of CYP3A5 polymorphisms on haloperidol treatment in patients with
alcohol addiction.
AB - Background: Isoenzymes CYP2D6 and CYP3A4, the activity of which varies widely,
are involved in metabolism of haloperidol and may influence its profile of
efficacy and safety. Objective: The primary aim of this study was to estimate the
relationship between CYP3A5 gene polymorphism, activity of the CYP3A isoenzyme,
and the risk of development of adverse drug reactions by haloperidol in patients
with alcohol abuse. Methods: Sixty-six male alcohol-addicted patients
participated in the study. The safety of haloperidol was evaluated by Udvalg for
Kliniske Undersogelser Side Effect Rating Scale (UKU) and Simpson-Angus Scale for
extrapyramidal symptoms (SAS). The activity of CYP3A was evaluated by determining
the concentrations of an endogenous substrate of this isoenzyme (cortisol) and
its urinary metabolite (6-beta-hydroxycortisol, 6-B-HC). Genotyping of CYP3A5*3
was performed by real-time polymerase chain reaction with allele-specific
hybridization. Results: The frequency of A-allele occurrence in Russian
population was very poor (2.27%). CYP3A5*3 polymorphism had no influence on
safety profile indicators of haloperidol (UKU scale: p=0.55, SAS scale: p=0.64).
In addition, there was no statistical significant difference between the values
of indexes of the metabolic ratio (6-B-HC/cortisol) in groups with different
genotypes of CYP3A5*3: GG 5.00 (3.36; 6.39) vs AG 5.26 (2.10; 6.78) (p=0.902).
Conclusion: The frequency of A-allele occurrence of CYP3A5*3 in Russian
population is very poor, and it has no high influence on the safety of
haloperidol treatment; therefore, there are no reasons to take this polymorphism
into account in patients with alcohol addiction who receive haloperidol.
PMID- 29343980
TI - Peripheral and spinal TRPA1 channels contribute to formalin-induced long-lasting
mechanical hypersensitivity.
AB - Background: Transient receptor potential ankyrin 1 (TRPA1) is a non-selective
cation channel expressed by a subset of nociceptive neurons that acts as a
multimodal receptor. Its activity contributes to modulate nociceptive
transmission in acute inflammatory pain. However, the role of this channel in
chronic pain has been less studied. The purpose of this study was to investigate
the local peripheral and spinal participation of TRPA1 channels in formalin
induced long-lasting hypersensitivity. Materials and methods: Formalin (1%)
induced chronic hypersensitivity was determined by the application of von Frey
filaments to ipsilateral and contralateral paws and through pharmacological
testing using a selective TRPA1 blocker (A-967079). TRPA1 expression in the
dorsal root ganglion (DRG) and spinal cord was analyzed by Western blotting.
Results: Formalin (1%) injection produced acute flinching behavior (1 h) as well
as secondary allodynia and hyperalgesia (12 days). Local peripheral pretreatment
(10 min before) or posttreatment (6 days later) with A-967079 (1-100 uM)
partially prevented and reversed, respectively, in a dose-dependent manner, long
lasting secondary mechanical allodynia and hyperalgesia evoked by 1% formalin.
Likewise, intrathecal pretreatment or posttreatment with A-967079 partially
prevented and reversed, respectively, formalin-induced long-lasting
hypersensitivity. A-967079 (100 uM) completely abolished the pro-nociceptive
effect of formalin (adjusted to pH 7.4). Finally, formalin injection increased
TRPA1 protein expression in the DRG and spinal cord. Conclusion: Results indicate
that TRPA1 expressed in the DRG and spinal cord plays a relevant role in formalin
induced long-lasting secondary nociceptive hypersensitivity.
PMID- 29343981
TI - Assessment of pain score and specimen adequacy for ultrasound-guided fine-needle
aspiration biopsy of thyroid nodules.
AB - Objective: The aim of this study was to evaluate pain scores and specimen
adequacy for ultrasound-guided fine-needle aspiration biopsy (US-FNAB) of thyroid
nodules without and with local anesthesia (LA). Materials and methods: The US
FNAB procedure was performed on 183 patients with and without LA. One puncture
was made for solid nodules, and if patients could tolerate it, a two-puncture
technique was used for nodules with a cystic change. Four-point verbal rating
scores were assessed by a nursing assistant after completion of US-FNAB. To be an
adequate specimen, at least six groups of follicular cells are required, and each
group should contain at least 10 cells. Results: Immediately after US-FNAB, 92%
of patients with LA and 80% without LA reported no or mild pain (p=0.01). Most
patients tolerated the procedure well, with no pain (82.5%) reported 5 minutes
after the procedure. In univariate logistic regression, irregular boundary (odds
ratio [OR]: 2.52, 95% confidence interval [CI]: 1.04-6.06, p=0.04), calcification
(OR: 2.86, 95% CI: 1.06-7.76, p=0.04), and LA (OR: 0.35, 95% CI: 0.15-0.86,
p=0.02) were significantly associated with immediate moderate or severe pain.
Specimen adequacy was significantly associated with age (OR: 0.95, 95% CI: 0.92
0.97, p<0.01), heterogeneous echo-texture (OR: 1.76, 95% CI: 1.23-5.17, p=0.01),
predominate solid architecture (OR: 2.78, 95% CI: 1.42-5.41, p<0.01), and the use
of LA (OR: 3.34, 95% CI: 1.70-6.56, p<0.01). In multivariate logistic regression,
patients receiving LA had lower risk of moderate or severe pain (OR: 0.25, 95%
CI: 0.09-0.67, p=0.01) and higher chances of specimen adequacy (OR: 4.84, 95% CI:
2.17-10.7, p<0.01) compared to patients who did not receive LA. Conclusion: US
FNAB is a safe procedure, and most patients report no pain 5 minutes after the
procedure. The use of LA was associated with lower immediate pain scales and
higher specimen adequacy.
PMID- 29343983
TI - Does transcutaneous electrical nerve stimulation reduce pain and improve quality
of life in patients with idiopathic chronic orchialgia? A randomized controlled
trial.
AB - Background: Chronic orchialgia is defined as testicular pain, which may be either
unilateral or bilateral, lasting for more than 3 months. It disturbs a patient's
daily activities and quality of life (QoL), inciting the patient to search for
treatments to alleviate the pain. It is estimated that 25% of chronic orchialgia
cases are idiopathic. Purpose: The purpose of this study was to investigate how
effective transcutaneous electrical nerve stimulation (TENS) is in pain reduction
and how it consequently affects the QoL in patients with idiopathic chronic
orchialgia (ICO). Patients and methods: Seventy-one patients were randomly
assigned to group A (study group), which included 36 patients who received TENS
and analgesia, and group B (control group), which included 35 patients who
received analgesia only. The outcome measures were the participants' demographic
data and results of the visual analog scale (VAS) and QoL questionnaire. These
outcomes were measured before and after 4 weeks of treatment and at 2-month
follow-up. Results: The results showed that compared to pretreatment, there was a
significant reduction in pain postintervention and at 2-month follow-up in group
A (P<0.0001 and <0.001, respectively; F=7.1) as well as a significant improvement
in QoL at these time points (P<0.0001 and <0.0001, respectively). There were no
significant differences in the VAS score and QoL in group B at different time
points of evaluation. Conclusion: The findings indicate that TENS is effective in
reducing pain and improving patients' QoL in cases of ICO. TENS is an easy-to
use, effective, noninvasive, and simple method for ICO-associated pain control
and QoL improvement.
PMID- 29343982
TI - Increased theta band EEG power in sickle cell disease patients.
AB - Objective: Pain is a major issue in the care of patients with sickle cell disease
(SCD). The mechanisms behind pain and the best way to treat it are not well
understood. We studied how electroencephalography (EEG) is altered in SCD
patients. Methods: We recruited 20 SCD patients and compared their resting state
EEG to that of 14 healthy controls. EEG power was found across frequency bands
using Welch's method. Electrophysiological source imaging was assessed for each
frequency band using the eLORETA algorithm. Results: SCD patients had increased
theta power and decreased beta2 power compared to controls. Source localization
revealed that areas of greater theta band activity were in areas related to pain
processing. Imaging parameters were significantly correlated to emergency
department visits, which indicate disease severity and chronic pain intensity.
Conclusion: The present results support the pain mechanism referred to as
thalamocortical dysrhythmia. This mechanism causes increased theta power in
patients. Significance: Our findings show that EEG can be used to quantitatively
evaluate differences between controls and SCD patients. Our results show the
potential of EEG to differentiate between different levels of pain in an unbiased
setting, where specific frequency bands could be used as biomarkers for chronic
pain.
PMID- 29343984
TI - Appropriateness of sham or placebo acupuncture for randomized controlled trials
of acupuncture for nonspecific low back pain: a systematic review and meta
analysis.
AB - Objectives: To establish whether sham acupuncture (SA) or placebo acupuncture
(PA) is more efficacious for reducing low back pain (LBP) than other routine
treatments and to discuss whether SA or PA is appropriate for randomized
controlled trials of acupuncture for LBP. Methods: Six databases were searched on
31 May 2017. We included only randomized controlled trials of adults with LBP and
lower back myofascial pain syndrome. The studies had at least two control arms: a
sham-controlled acupuncture arm and a routine care or waiting list arm (people
who did not receive acupuncture until the end of treatment). Trials were combined
using meta-analysis methods when the data allowed statistical pooling. Pooled
effect sizes were calculated by random effects models. Results: This review
identified 7 trials (1768 participants); all were included in the meta-analysis.
We found statistically significant differences in pain reduction post
intervention between SA or PA and routine care or a waiting list, with a
standardized mean difference of -0.36 (95% CI -0.54 to -0.18; I2 statistic=16%;
participants=624; studies=6) for the Visual Analog Scale and -0.35 (95% CI -0.49
to -0.20; I2 statistic=0%; participants=736; studies=1) for the Chronic Pain
Grade Scale; however, no significant difference was observed between SA or PA and
routine care or no treatment for post-intervention function. Conclusion: Compared
with routine care or a waiting list, SA or PA was more efficacious for pain
relief post-intervention. Concluding that SA or PA is appropriate for acupuncture
research would be premature. Guidelines evaluating SA or PA control methods are
needed to determine the specific effect of acupuncture over placebo.
PMID- 29343985
TI - Bioactive chromone constituents from Vitex negundo alleviate pain and
inflammation.
AB - Background: Vitex negundo L. has been widely studied for its beneficial effect in
inflammatory and pain conditions. The present study describes the isolation of
two new bioactive chromone constituents from V. negundo and their in vivo
evaluation for anti-inflammatory and antinociceptive activities. Methods: Two new
chromone derivatives, namely, methyl 3-(2-(5-hydroxy-6-methoxy-4-oxo-4H-chromen-2
yl)ethyl)benzoate (1) and 3-(1-hydroxy-2-(5-hydroxy-6-methoxy-4-oxo-4H-chromen-2
yl)ethyl)benzoic acid (2) were isolated from V. negundo and their structures were
determined through various spectroscopic techniques including mass spectrometry,
UV, IR, 1H NMR, 13C NMR, and two-dimensional-NMR like correlation spectroscopy
and heteronuclear multiple bond correlation techniques. The isolated compounds (1
2) were tested for their prospective antinociceptive activity in acetic acid
induced abdominal constriction assay and anti-inflammatory activity in the
carrageenan-induced paw edema assay in mice. Results: Significant attenuation
(P<0.001) of tonic visceral nociception was demonstrated by compound 1 and 2 at
doses of 50 and 100 mg/kg. At similar doses, these compounds (1-2) also showed
potent amelioration (P<0.001) of carrageenan-induced paw swelling. Conclusion:
The isolated chromone derivatives (1-2) from V. negundo are able to alleviate
nociception and inflammation and the findings corroborated that V. negundo may be
used as a potential source of antinociceptive and anti-inflammatory candidates.
PMID- 29343986
TI - Radiotherapy for esophageal carcinoma: dose, response and survival.
AB - Esophageal cancer (EC) is an extremely aggressive, lethal malignancy that is
increasing in incidence worldwide. At present, definitive chemoradiotherapy is
accepted as the standard treatment for locally advanced EC. The EC guidelines
recommend a radiation dose of 50.4 Gy for definitive treatment, yet the outcomes
for patients who have received standard-dose radiotherapy remain unsatisfactory.
However, some studies indicate that a higher radiation dose could improve local
tumor control, and may also confer survival benefits. Some studies, however,
suggest that high-dose radiotherapy does not bring survival benefit. The
available data show that most failures occurred in the gross target volume
(especially in the primary tumor) after definitive chemoradiation. Based on those
studies, we hypothesize that at least for some patients, more intense local
therapy may lead to better local control and survival. The aim of this review is
to evaluate the radiation dose, fractionation strategies, and predictive factors
of response to therapy in functional imaging for definitive chemoradiotherapy in
esophageal carcinoma, with an emphasis on seeking the predictive model of
response to CRT and trying to individualize the radiation dose for EC patients.
PMID- 29343987
TI - Performance of the LACE index to predict 30-day hospital readmissions in patients
with chronic obstructive pulmonary disease.
AB - Background and objective: Patients hospitalized for acute exacerbation of chronic
obstructive pulmonary disease (COPD) have a high 30-day hospital readmission
rate, which has a large impact on the health care system and patients' quality of
life. The use of a prediction model to quantify a patient's risk of readmission
may assist in directing interventions to patients who will benefit most. The
objective of this study was to calculate the rate of 30-day readmissions and
evaluate the accuracy of the LACE index (length of stay, acuity of admission, co
morbidities, and emergency department visits within the last 6 months) for 30-day
readmissions in a general hospital population of COPD patients. Methods: All
patients admitted with a principal diagnosis of COPD to Liverpool Hospital, a
tertiary hospital in Sydney, Australia, between 2006 and 2016 were included in
the study. A LACE index score was calculated for each patient and assessed using
receiver operator characteristic curves. Results: During the study period, 2,662
patients had 5,979 hospitalizations for COPD. Four percent of patients died in
hospital and 25% were readmitted within 30 days; 56% of all 30-day readmissions
were again due to COPD. The most common reasons for readmission, following COPD,
were heart failure, pneumonia, and chest pain. The LACE index had moderate
discriminative ability to predict 30-day readmission (C-statistic =0.63).
Conclusion: The 30-day hospital readmission rate was 25% following
hospitalization for COPD in an Australian tertiary hospital and as such
comparable to international published rates. The LACE index only had moderate
discriminative ability to predict 30-day readmission in patients hospitalized for
COPD.
PMID- 29343988
TI - Does breast density measured through population-based screening independently
increase breast cancer risk in Asian females?
AB - Purpose: The purpose of this study was to investigate the effects of breast
density on breast cancer risk among women screened via a nationwide mammographic
screening program. Patients and methods: We conducted a nested case-control study
for a randomly selected population of 1,561 breast cancer patients and 6,002
matched controls from the National Cancer Screening Program. Breast density was
measured and recorded by two independent radiologists using the Breast Imaging
Reporting and Data System (BI-RADS). Associations between BI-RADS density and
breast cancer risk were evaluated according to screening results, time elapsed
since receiving non-recall results, age, and menopausal status after adjusting
for possible covariates. Results: Breast cancer risk for women with extremely
dense breasts was five times higher (adjusted odds ratio [aOR] =5.0; 95%
confidence interval [CI]) =3.7-6.7) than that for women with an almost entirely
fatty breast, although the risk differed between recalled women (aOR =3.3, 95% CI
=2.3-3.6) and women with non-recalled results (aOR =12.1, 95% CI =6.3-23.3, P
heterogeneity =0.001). aORs for BI-RADS categories of breast density were similar
when subjects who developed cancer after showing non-recall findings during
initial screening were grouped according to time until cancer diagnosis
thereafter (<1 and >=1 year). The prevalence of dense breasts was higher in
younger women, and the association between a denser breast and breast cancer was
stronger in younger women (heterogeneously dense breast: aOR =7.0, 95% CI =2.4
20.3, women in their 40s) than older women (aOR =2.5, 95% CI =1.1-6.0, women in
their 70s or more). In addition, while the positive association remained,
irrespective of menopausal status, the effect of a dense breast on breast cancer
risk was stronger in premenopausal women. Conclusion: This study confirmed an
increased risk of breast cancer with greater breast density in Korean women which
was consistent regardless of BI-RADS assessment category, time interval after
initially non-recall results, and menopausal status.
PMID- 29343989
TI - Comparison of the performance of five screening methods for sarcopenia.
AB - Background: Sarcopenia leads to serious adverse health consequences. There is a
dearth of screening tools for this condition, and performances of these
instruments have rarely been evaluated. Our aim was to compare the performance of
five screening tools for identifying elders at risk of sarcopenia against five
diagnostic definitions. Subjects and methods: We gathered cross-sectional data of
elders from the SarcoPhAge ("Sarco"penia and "Ph"ysical Impairment with Advancing
"Age") study. Lean mass was measured with X-ray absorptiometry, muscle strength
with a dynamometer and physical performance with the Short Physical Performance
Battery (SPPB) test. Performances of screening methods were described using
sensitivity, specificity, positive predictive value (PPV), negative predictive
value (NPV) and area under the curve (AUC), according to five diagnostic
definitions of sarcopenia. For each screening tool, optimal cutoff points were
computed using two methods. Results: A total of 306 subjects (74.8+/-5.9 years,
59.5% women) were included. The prevalence of sarcopenia varied from 5.7% to
16.7% depending on the definition. The best sensitivity (up to 100%) and the best
NPV (up to 99.1%) were obtained with the screening test of Ishii et al,
regardless of the definition applied. The highest AUC (up to 0.914) was also
demonstrated by the instrument of Ishii et al. The most specific tool was the
algorithm of the European Working Group on Sarcopenia in Older People (EWGSOP; up
to 91.1%). All NPVs were above 87.0%, and all PPVs were below 51.0%. New cutoffs
related to each screening instrument were also proposed to better discriminate
sarcopenic individuals from non-sarcopenic individuals. Conclusion: Screening
instruments for sarcopenia can be relevantly used in clinical practice to make
sure to identify individuals who do not suffer from the syndrome. The screening
test of Ishii et al showed better properties in terms of distinguishing those at
risk of sarcopenia from those who were not at risk.
PMID- 29343990
TI - Emerging evidence on the link between depressive symptoms and bone loss in
postmenopausal women.
AB - Osteoporosis and depression are major health problems of crisis proportions in
postmenopausal women. Researchers have established a relationship between bone
loss and depression, although few studies have focused on postmenopausal women.
The purposes of this integrative review were to synthesize and summarize the
available literature on: 1) the associations between bone loss and depression in
postmenopausal women; and 2) potential variables that impact the associations
between bone loss and depression in postmenopausal women. After searching the
databases PubMed, CINAHL, Embase, and the Cochrane library between 2007 and 2017,
12 articles met the inclusion criteria. The majority of the included studies
supported the relationship between depression and bone loss in postmenopausal
women, although little information is offered as to why this relationship exists.
This review summarizes the research that has been completed on depression and
bone loss in postmenopausal women and identifies gaps in the literature. These
findings will aid in the planning of future research and the development of
health care recommendations.
PMID- 29343991
TI - Trends and inequities in use of maternal health care services in Indonesia, 1986
2012.
AB - Purpose: Overall health status indicators have improved significantly over the
past three decades in Indonesia. However, the country's maternal mortality ratio
remains high with a stark inequality by region. Fewer studies have explored
access inequity in maternal health care service over time using multiple
inequality markers. In this study, we analyzed Indonesian Demographic and Health
Survey (DHS) data to explore trends and inequities in use of any antenatal care
(ANC), four or more ANC (ANC4+), institutional birth, and cesarean section (c
section) birth in Indonesia during 1986-2012 to inform policy for future
strategies ending preventable maternal deaths. Methods: Indonesian DHS data from
1991, 1994, 1997, 2002/3, 2007, and 2012 surveys were downloaded, merged, and
analyzed. Inequity was measured in terms of variation in use by asset quintile,
parental education, urban-rural location, religion, and region. Trends in use
inequities were assessed plotting changes in rich:poor ratio, rich:poor
difference, and concentration indices over period based on asset quintiles.
Sociodemographic determinants for service use were explored using multivariable
logistic regression analysis. Findings: Between 1986 and 2012, institutional
birth rate increased from 22% to 73% and c-section rate from 2% to 16%. Private
sector was increasingly contributing in maternal health. There were significant
access inequities by asset quintile, parental education, area of residence, and
geographical region. The richest women were 5.45 times (95% CI: 4.75-6.25) more
likely to give birth in a health facility and 2.83 times (95% CI: 2.23-3.60) more
likely to give birth by c-section than their poorest counterparts. Urban women
were 3 times more likely to use institutional birth and 1.45 times more likely to
give birth by c-section than rural women. Use of all services was higher in Java
and Bali than in other regions. Access inequity was narrowing over time for use
of ANC and institutional birth but not for c-section birth. Conclusion: Ongoing
pro-poor health-financing strategies should be strengthened with introduction of
innovative ways to monitor access, equity, and quality of care in maternal
health.
PMID- 29343992
TI - Validation of BP devices QardioArm(r) in the general population and Omron M6
Comfort(r) in type II diabetic patients according to the European Society of
Hypertension International Protocol (ESH-IP).
AB - Background: Following the European Society of Hypertension International Protocol
(ESH-IP) Revision 2010, QardioArm(r) and Omron M6 Comfort IT(r) oscillometric
devices were evaluated in the general population and in patients with type II
diabetes, respectively, for self-blood pressure (BP) measurement. Methods: Both
devices, QardioArm(r) and Omron M6 Comfort(r), measure BP at the brachial level.
The ESH-IP Revision 2010 includes a total number of 33 subjects. For each
measure, the difference between observer and device BP values was calculated. In
all, 99 pairs of BP differences are classified into three categories (<=5, <=10,
and <=15 mmHg). The protocol procedures were followed precisely. Results:
QardioArm(r) and Omron M6 Comfort(r) fulfilled the requirements of the ESH-IP and
passed the validation process successfully. For QardioArm(r), a total of 69 out
of 99 comparisons for systolic blood pressure (SBP) showed an absolute difference
within 5 mmHg and 82 out of 99 for diastolic blood pressure (DBP). As for Omron
M6 Comfort(r), a total of 83 out of 99 comparisons for SBP showed an absolute
difference within 5 mmHg and 77 out of 99 for DBP. The mean differences between
the device and mercury readings were 0.7+/-5.9 mmHg for SBP and 0.3+/-4.1 mmHg
for DBP for QardioArm(r) and -1.4+/-4.7 mmHg for SBP and -2.1+/-4.3 mmHg for DBP
for Omron M6 Comfort(r). With regard to part 2 of ESH-IP 2010, 27 out of 33
subjects had a minimum of two out of three measurements within 5 mmHg difference
for SBP and 31 out of 33 subjects for DBP for the QardioArm(r), and 29 out of 33
patients had a minimum of two out of three measurements within 5 mmHg difference
for SBP and 26 out of 33 patients for DBP for Omron M6 Comfort(r). Conclusion:
QardioArm(r) and Omron M6 Comfort(r) readings differing from the mercury standard
by <5, 10, and 15 mmHg fulfill the ESH-IP Revision 2010 requirements.
Consequently, these two devices are suitable for use in the general population
and non-insulin-dependent type II diabetic patients, respectively.
PMID- 29343993
TI - Management of disseminated intravascular coagulation: current insights on
antithrombin and thrombomodulin treatments.
AB - Sepsis and septic shock are frequently complicated by disseminated intravascular
coagulation (DIC), which decreases the survival rate of patients with sepsis. In
the past, large international randomized controlled trials (RCTs) using
physiological anticoagulants for sepsis-induced DIC were not performed; however,
RCTs have been conducted for sepsis and/or septic shock. In these trials,
physiological anticoagulants did not show any beneficial effects compared with
placebo for the treatment of sepsis and/or septic shock. In Japan, DIC treatments
using antithrombin (AT) and/or recombinant human soluble thrombomodulin (rhTM)
are common for patients with sepsis-induced DIC. Recently, large propensity score
analyses demonstrated that AT and rhTM improved survival in patients with sepsis
induced DIC. Furthermore, post hoc analyses and meta-analyses that selected
patients with sepsis-induced DIC from the previous large international RCTs
indicated that physiological anticoagulants improved survival without increasing
the associated sepsis-induced DIC bleeding. DIC treatments, such as AT and rhTM,
may demonstrate beneficial effects when they are targeted at patients with sepsis
induced DIC only.
PMID- 29343994
TI - Calibration and validation of an item bank for measuring general physical
function of patients in medical rehabilitation settings.
AB - Objective: The objective of this study was to report the item response theory
(IRT) calibration of an 18-item bank to measure general physical function (GPF)
in a wide range of conditions and evaluate the validity of the derived scores.
Methods: All 18 items were administered to a large sample of patients (n=2337)
who responded to the items in the context of their outpatient rehabilitation
care. The responses, collected 1997- 2000, were modeled using the graded response
model, an IRT model appropriate for items with two or more response options.
Inter-item consistency was evaluated based on Cronbach's alpha and item to total
correlations. Validity of scores was evaluated based on known-groups comparisons
(age, number of health problems, symptom severity). The strength of a single,
general factor was evaluated using a bi-factor model. Results were used to
evaluate IRT assumption and as an indicator of construct validity. Local
independence of item responses was also evaluated. Results: Response data met the
assumptions of unidimensionality and local independence. Explained common
variance of a single general factor was 0.88 (omega hierarchical =0.86). Only two
of the 153 pairs of item residuals were flagged for local dependence. Inter-item
consistency was high (0.93) as were item to total correlations (mean =0.61).
Substantial variation was found in both IRT location (difficulty) and
discrimination parameters. All omnibus known-groups comparisons were
statistically significant (p<0.001). Conclusion: Item responses fit the IRT
unidimensionality assumptions and were internally consistent. The usefulness of
GPF scores in discriminating among patients with different levels of physical
function was confirmed. Future studies should evaluate the validity of GPF scores
based on an adaptive administration of items.
PMID- 29343995
TI - HumanMethylation450K Array-Identified Biomarkers Predict Tumour
Recurrence/Progression at Initial Diagnosis of High-risk Non-muscle Invasive
Bladder Cancer.
AB - Background: High-risk non-muscle invasive bladder cancer (HR-NMIBC) is a
clinically unpredictable disease. Despite clinical risk estimation tools, many
patients are undertreated with intra-vesical therapies alone, whereas others may
be over-treated with early radical surgery. Molecular biomarkers, particularly
DNA methylation, have been reported as predictive of tumour/patient outcomes in
numerous solid organ and haematologic malignancies; however, there are few
reports in HR-NMIBC and none using genome-wide array assessment. We therefore
sought to identify novel DNA methylation markers of HR-NMIBC clinical outcomes
that might predict tumour behaviour at initial diagnosis and help guide patient
management. Patients and methods: A total of 21 primary initial diagnosis HR
NMIBC tumours were analysed by Illumina HumanMethylation450 BeadChip arrays and
subsequently bisulphite Pyrosequencing. In all, 7 had not recurred at 1 year
after resection and 14 had recurred and/or progressed despite intra-vesical BCG.
A further independent cohort of 32 HR-NMIBC tumours (17 no recurrence and 15
recurrence and/or progression despite BCG) were also assessed by bisulphite
Pyrosequencing. Results: Array analyses identified 206 CpG loci that segregated
non-recurrent HR-NMIBC tumours from clinically more aggressive
recurrence/progression tumours. Hypermethylation of CpG cg11850659 and
hypomethylation of CpG cg01149192 in combination predicted HR-NMIBC recurrence
and/or progression within 1 year of diagnosis with 83% sensitivity, 79%
specificity, and 83% positive and 79% negative predictive values. Conclusions:
This is the first genome-wide DNA methylation analysis of a unique HR-NMIBC
tumour cohort encompassing known 1-year clinical outcomes. Our analyses
identified potential novel epigenetic markers that could help guide individual
patient management in this clinically unpredictable disease.
PMID- 29343996
TI - Does HLA-B27 Status Influence Ankylosing Spondylitis Phenotype?
AB - The association of HLA-B27 with ankylosing spondylitis (AS) remains as one of the
intriguing models that could exist between a molecule and human disease in
medicine. Although it was reported in 1973, its contribution to AS and related
spondyloarthritis continues to be a major challenge for scientific community. It
is important to understand its etiopathogenic mechanism and its functions in
these diseases. Although the diagnostic and prognostic roles of HLA-B27 in AS are
still debated, there is an increasing interest for HLA-B27-based effects
especially in HLA-B27(+) patients with AS. This review will focus in the
examination of published reports regarding the influence of HLA-B27 status on the
demographic and clinical features in AS, with specific interest to its role on AS
severity.
PMID- 29343997
TI - Hospitalisation in Patients With Heart Failure With Preserved Ejection Fraction.
AB - Heart failure is highly prevalent with more than 50% of cases being patients with
a preserved ejection fraction (HFPEF), a figure that is projected to increase due
to the changing risk factor landscape, in particular the ageing population.
Overall mortality is similar to patients with heart failure with reduced ejection
fraction (HFREF), as are the rates of hospitalisation. Patients with HFPEF have
more comorbid conditions with fewer therapeutic options available. In this
review, we explore the epidemiology of hospitalisation of HFPEF, the impact of
current treatment modalities, and the potential of future therapies.
PMID- 29343998
TI - Rationale and Design for a Monocentric Prospective Study: Sleep Apnea Diagnosis
Using a Novel Pacemaker Algorithm and Link With Aldosterone Plasma Level in
Patients Presenting With Diastolic Dysfunction (SAPAAD Study).
AB - Previous studies showed good agreement between pacemaker respiratory disturbance
index (RDI) and polysomnography for diagnosis of severe sleep apnea (SA). The aim
of this study is to investigate the diagnostic accuracy of RDI compared with
apnea-hypopnea index (AHI) from a cardiorespiratory sleep study for the diagnosis
of severe SA within patients requiring a pacemaker and meeting diastolic
dysfunction criteria. Secondary objectives are as follows: correlation between
plasma aldosterone level and SA severity, diagnostic accuracy of RDI for moderate
SA, prevalence of SA among patients with diastolic dysfunction, occurrence of
arrhythmias, and improvement of RDI with continuous positive airway pressure
therapy. We designed a monocentric prospective nonrandomized study of prevalent
cases to include 68 patients with a 6-month follow-up. Both RDI and AHI will be
compared 2 months after implantation and after 1 month of continuous positive
airway pressure treatment in patients with severe SA. This is the first study
that examines diagnostic accuracy of pacemaker algorithm for the diagnosis of SA
and correlation with plasma aldosterone levels in patients with diastolic
dysfunction. Protocol version: V04. 04/04/2017 Trial registration:
ClinicalTrials.gov NCT02751021.
PMID- 29343999
TI - Targeted Treatment With Radio Frequency Ablation for Lingual Tonsil.
AB - Objectives: Benign enlargement of the lingual tonsils due to various causes may
cause symptoms that warrant treatment. Conventional lingual tonsillectomy remains
a challenging procedure, and there is no established standard procedure. We aimed
to review the patients receiving different methods of lingual tonsil surgery for
various indications at our institute. Methods: Retrospective clinical data on all
patients with an ablative operation of the tongue base during the 8-year period
between 2007 and 2014 at the Helsinki University Hospital, Helsinki, Finland,
were reviewed. The larger cohort comprised 35 patients, of whom 26 were men
(74%). Ten patients had undergone solely lingual tonsil radio frequency ablation
(LTRFA). The minimum follow-up time for all patients was 2 years. Results: Of the
10 patients, 5 patients with LTRFA had been operated on because of symptomatic
lingual tonsil hypertrophy and 5 because of periodic fever associated with
possible lingual tonsil involvement. In 2 of the 5 patients with periodic fever,
the fever cycles ended after the operation. Of the 5 patients, 3 patients with
symptomatic lingual tonsil hypertrophy have been non-symptomatic after 1 to 3
treatment sessions. The last 2 patients continue to have persistent symptoms.
There were no major complications. Conclusions: Development of new approaches for
the management of various lingual tonsil conditions is warranted. Lingual tonsil
volume reduction by LTRFA seems to be a treatment alternative with low morbidity
but with limited curative effect only.
PMID- 29344000
TI - Visible-Near Infrared Spectroscopic Assessment of Urogenital Tissue in
Premenopausal and Postmenopausal Women.
AB - Background: A clinical study was conducted to evaluate the feasibility of using
visible and near-infrared (NIR) spectroscopy as a potential noninvasive measure
of genital skin health in premenopausal and postmenopausal women. Methods: A
total of 45 female subjects (aged 21-70 years), all of whom gave fully informed
consent to participate, were enrolled in the study and assigned to 1 of 3 groups:
15 premenopausal (Pre-M), 15 postmenopausal receiving hormone replacement therapy
(Post-M HRT), and 15 postmenopausal receiving no form of hormone replacement
therapy (Post-M non-HRT). Spectral measurements were taken at the vaginal mucosa,
and spectral data were evaluated for the erythema index (EI), hemoglobin index
(HI), bilirubin/beta-carotene, and melanin. The color index (CI; calculated as
the ratio of absorbance at 480 nm/540 nm) was also determined. Results were
compared with previously published results on biomarkers and physical
characteristic of genital tissue measured on the same groups of women. Results:
Spectral measurements from the Post-M Non-HRT subjects indicated a significant
reduction in HI compared with the Pre-M group (P = .0003) and to the Post-M HRT
group (P < .0001). Similarly, EI was reduced in the Post-M Non-HRT (P < .0001 and
P = .0041 for the Pre-M and Post-M HRT groups, respectively). In contrast, the
Post-M Non-HRT subjects exhibited a significant increase in beta-carotene
compared with the Pre-M subjects (P = .0098). Bilirubin and melanin were not
significantly affected. The Post-M Non-HRT group exhibited a significant increase
in CI, indicating a shift away from the hemoglobin absorption region (510-620 nm
wavelength) and toward the bilirubin/beta-carotene absorption region (450-490 nm
wavelength). This change was significant when compared with both the Pre-M group
(P < .0001) and the Post-M HRT group (P = .0048). The changes in spectral
measurements were consistent with previously reported changes in physical
parameters (vaginal atrophy, increased pH, decreased skin temperature) and with
decreased concentrations of the biomarkers histamine and histidine. Conclusions:
Hemodynamic spectral characteristics differ in postmenopausal vaginal tissue
compared with tissue in premenopausal women, with decreased absorbance in the
hemoglobin absorption region (510-620 nm wavelength) and an increased absorbance
in the bilirubin/beta-carotene absorption region (450-490 nm wavelength). A
change in absorbance in the visible and NIR wavelengths is a promising,
additional measure of genital skin health related to menopause and vulvovaginal
atrophy.
PMID- 29344001
TI - Intraventricular Hemorrhage Due to Coagulopathy After Vitamin K Administration in
a Preterm Infant With Maternal Crohn Disease.
AB - Intraventricular hemorrhage (IVH) is a devastating morbidity in preterm infants
and can result in poor neurodevelopmental outcomes. Intraventricular hemorrhage
usually occurs within 72 hours after birth; post-acute-phase IVH (>1 week after
birth) is uncommon. Development of the hemostatic system in fetuses and neonates
is an age-dependent evolving process, and the neonatal hemostatic system is
characterized by low levels of vitamin K-dependent factors, with further
reduction caused by prematurity. Importantly, a severe coagulation deficiency can
be a major contributing factor of IVH. Active maternal Crohn disease (CD) during
pregnancy causes malnutrition via enteral malabsorption; this may include vitamin
K deficiency, resulting in fetal vitamin K deficiency. We herein describe a
preterm infant who was born to a mother with CD and developed post-acute-phase
IVH due to coagulopathy despite vitamin K administration.
PMID- 29344002
TI - The journey from clinician to undergraduate medical educator involves four
patterns of transformation.
AB - Objectives: Traditionally, teaching is part of a clinician's job. Some
practitioners recognize the teaching activity as rewarding. This study explored
the ways clinical practitioners experience their journey from clinicians to
medical teachers, analyzing their prior experiences of teaching and learning,
conceptions of good teaching and learning, perceptions of learning environments,
and finally, how those factors influence their approaches to teaching. Methods:
Data for phenomenographic analysis were collected through semi-structured
interviews conducted in Spanish and administered to twelve clinical teachers in
three medical schools in Colombia. Results: Through sequential phases of
analysis, we constructed a conceptual diagram to identify critical concepts,
themes, and categories that describe patterns that clinicians adopt during their
journey to become medical teachers. We identified two themes and four patterns
that describe the journey from practitioner to medical teacher: the identity
theme, referring to "what" practitioners showed as the object of the journey and
the changing process theme referring to "how" participants adopt changes during
the journey. We describe four patterns that describe the journey that physicians
adopt when exposed to the experience of clinical teaching. Conclusion: It is
possible to identify two themes and to devise at least four patterns in ways of
experiencing the journey to medical teacher. These patterns are not a fixed set
of characteristics, but rather a spectrum of experiences. Taking into
consideration the professional identity of clinical teachers and the path of
their teaching process change, it might be possible to devise better strategies
for teaching development activities.
PMID- 29344003
TI - A medical student in private practice for a 1-month clerkship: a qualitative
exploration of the challenges for primary care clinical teachers.
AB - Purpose: The predicted shortage of primary care physicians emphasizes the need to
increase the family medicine workforce. Therefore, Swiss universities develop
clerkships in primary care physicians' private practices. The objective of this
research was to explore the challenges, the stakes, and the difficulties of
clinical teachers who supervised final year medical students in their primary
care private practice during a 1-month pilot clerkship in Geneva. Methods: Data
were collected via a focus group using a semistructured interview guide.
Participants were asked about their role as a supervisor and their difficulties
and positive experiences. The text of the focus group was transcribed and
analyzed qualitatively, with a deductive and inductive approach. Results: The
results show the nature of pressures felt by clinical teachers. First,
participants experienced the difficulty of having dual roles: the more familiar
one of clinician, and the new challenging one of teacher. Second, they felt
compelled to fill the gap between the academic context and the private practice
context. Clinical teachers were surprised by the extent of the adaptive load,
cognitive load, and even the emotional load involved when supervising a trainee
in their clinical practice. The context of this rotation demonstrated its utility
and its relevance, because it allowed the students to improve their knowledge
about the outpatient setting and to develop their professional autonomy and their
maturity by taking on more clinical responsibilities. Conclusion: These findings
show that future training programs will have to address the needs of clinical
teachers as well as bridge the gap between students' academic training and the
skills needed for outpatient care. Professionalizing the role of clinical
teachers should contribute to reaching these goals.
PMID- 29344004
TI - Perceived organizational support and moral distress among nurses.
AB - Background: Moral distress is prevalent in the health care environment at
different levels. Nurses in all roles and positions are exposed to ethically
challenging conditions. Development of supportive climates in organizations may
drive nurses towards coping moral distress and other related factors. This study
aimed at determining the level of perceived organizational support and moral
distress among nurses and investigating the relationship between the two
variables. Methods: This was a correlational-descriptive study. A total of 120
nurses were selected using random quota sampling method. A demographic
questionnaire, Survey of Perceived Organizational Support, and Moral Distress
Scale were used to collect the data which were analyzed using descriptive and
analytical tests in SPSS20. Results: The mean perceived organizational support
was low (2.63 +/- 0.79). The mean moral distress was 2.19 +/- 0.58, which shows a
high level of moral distress. Moreover, Statistical analysis showed no
significant relationship between perceived organizational support and moral
distress (r = 0.01, p = 0.86). Conclusion: Given the low level of perceived
organizational support and high moral distress among nurses in this study, it is
necessary to provide a supportive environment in hospitals and to consider
strategies for diminishing moral distress.
PMID- 29344005
TI - Biological clocks: their relevance to immune-allergic diseases.
AB - The 2017 Nobel Prize for Physiology or Medicine, awarded for the discoveries made
in the past 15 years on the genetic and molecular mechanisms regulating many
physiological functions, has renewed the attention to the importance of circadian
rhythms. These originate from a central pacemaker in the suprachiasmatic nucleus
in the brain, photoentrained via direct connection with melanopsin containing,
intrinsically light-sensitive retinal ganglion cells, and it projects to
periphery, thus creating an inner circadian rhythm. This regulates several
activities, including sleep, feeding times, energy metabolism, endocrine and
immune functions. Disturbances of these rhythms, mainly of wake/sleep, hormonal
secretion and feeding, cause decrease in quality of life, as well as being
involved in development of obesity, metabolic syndrome and neuropsychiatric
disorders. Most immunological functions, from leukocyte numbers, activity and
cytokine secretion undergo circadian variations, which might affect
susceptibility to infections. The intensity of symptoms and disease severity show
a 24 h pattern in many immunological and allergic diseases, including rheumatoid
arthritis, bronchial asthma, atopic eczema and chronic urticaria. This is
accompanied by altered sleep duration and quality, a major determinant of quality
of life. Shift work and travel through time zones as well as artificial light
pose new health threats by disrupting the circadian rhythms. Finally, the field
of chronopharmacology uses these concepts for delivering drugs in synchrony with
biological rhythms.
PMID- 29344006
TI - Histone deacetylase 2 (HDAC2) attenuates lipopolysaccharide (LPS)-induced
inflammation by regulating PAI-1 expression.
AB - Background: Sepsis is a life-threatening organ dysfunction caused by dysregulated
host response to infection, and is primarily characterized by an uncontrolled
systemic inflammatory response. In the present study, we developed an effective
adjunct therapy mediated by a novel mechanism, to attenuate overt inflammation.
LPS-treated macrophages were adopted as an in vitro model of endotoxin-induced
inflammation during sepsis. Experiments were carried out using primary mouse
peritoneal macrophages and the murine macrophage cell line RAW264.7, to elucidate
the mechanisms by which HDAC2 modulates endotoxin-induced inflammation. Results:
Results revealed that PAI-1, TNF, and MIP-2 expression were inhibited by
theophylline, an HDAC2 enhancer, in a RAW macrophage cell line, following LPS
induced inflammation. Thus, HDAC2 plays an important role in immune defense by
regulating the expression of inflammatory genes via the c-Jun/PAI-1 pathway.
During LPS-induced inflammation, overexpression of HDAC2 was found to inhibit PAI
1, TNF, and MIP-2 expression. Following LPS stimulation, HDAC2 knockdown
increased nuclear translocation and DNA binding of c-Jun to the PAI-1 gene
promoter, thereby activating PAI-1 gene transcription. Furthermore, inhibition of
PAI-1 by TM5275 alone or in combination with theophylline notably suppressed TNF
and MIP-2 expression. Conclusion: HDAC2 can attenuate lipopolysaccharide-induced
inflammation by regulating c-Jun and PAI-1 expression in macrophages.
PMID- 29344007
TI - Four-factor prothrombin complex concentrate improves thrombin generation and
prothrombin time in patients with bleeding complications related to rivaroxaban:
a single-center pilot trial.
AB - Background: Direct oral anticoagulants (DOACs) pose a great challenge for
physicians in life-threatening bleeding events. The aim of this study was to test
the efficacy of reversing the DOAC rivaroxaban using four-factor PCC (prothrombin
complex concentrate), a non-specific reversing agent. Methods: Patients with life
threatening bleeding events during rivaroxaban treatment were included and
administered 25 U kg-1 of PCC. Blood samples were collected immediately prior to
as well as after PCC treatment at predefined time intervals. The primary endpoint
was defined as the difference in thrombin generation (TG) parameters ETP
(endogenous thrombin potential) and Cmax (peak thrombin generation) prior to and
ten minutes subsequent to PCC treatment. Results: Thirteen patients, of whom the
majority suffered from intra-cranial haemorrhage (ICH) or subdural haemorrhage
(SDH), were included and administered PCC. The results show that the ETP (TG)
significantly (p = 0.001) improved by 68% and Cmax (TG) by 54% (p = 0.001) during
PCC treatment. In addition, the Quick value (prothrombin time: QuickPT)
significantly improved by 28% and the activated partial thromboplastin time
(aPTT) was decreased by 7% ten minutes after PCC administration. Cmax was reduced
at baseline, but not ETP, aPTT or QuickPT. Lag time until initiation (TG, tlag),
thromboelastometry clotting time (CTEXTEM) and time to peak (TG, tmax) correlated
best with measured rivaroxaban levels and were out of normal ranges at baseline,
but did not improve after PCC administration. In 77% of the patients bleeding
(ICH/SDH-progression) ceased following PCC administration. During the study three
participants passed away due to other complications not related to PCC treatment.
The possibility of thrombosis formation was also evaluated seven days after
administering PCC and no thromboses were found. Conclusions: This study shows
that use of PCC improved ETP, Cmax, QuickPT and aPTT. However, of these
parameters, only Cmax was reduced at the defined baseline. It can be concluded
that CTEXTEM, tlag and tmax correlated best with the measured rivaroxaban levels.
The study drug was found to be safe. Nonetheless, additional studies specifically
targeting assessment of clinical endpoints should be performed to further confirm
these findings. Clinical trial registration: EudraCT trial No. 2013-004484-31.
PMID- 29344010
TI - Evidence Supporting No Dose Response of Mortality to Air Quality.
PMID- 29344008
TI - Understanding the factors that effect maximal fat oxidation.
AB - Lipids as a fuel source for energy supply during submaximal exercise originate
from subcutaneous adipose tissue derived fatty acids (FA), intramuscular
triacylglycerides (IMTG), cholesterol and dietary fat. These sources of fat
contribute to fatty acid oxidation (FAox) in various ways. The regulation and
utilization of FAs in a maximal capacity occur primarily at exercise intensities
between 45 and 65% VO2max, is known as maximal fat oxidation (MFO), and is
measured in g/min. Fatty acid oxidation occurs during submaximal exercise
intensities, but is also complimentary to carbohydrate oxidation (CHOox). Due to
limitations within FA transport across the cell and mitochondrial membranes, FAox
is limited at higher exercise intensities. The point at which FAox reaches
maximum and begins to decline is referred to as the crossover point. Exercise
intensities that exceed the crossover point (~65% VO2max) utilize CHO as the
predominant fuel source for energy supply. Training status, exercise intensity,
exercise duration, sex differences, and nutrition have all been shown to affect
cellular expression responsible for FAox rate. Each stimulus affects the process
of FAox differently, resulting in specific adaptions that influence endurance
exercise performance. Endurance training, specifically long duration (>2 h)
facilitate adaptations that alter both the origin of FAs and FAox rate.
Additionally, the influence of sex and nutrition on FAox are discussed. Finally,
the role of FAox in the improvement of performance during endurance training is
discussed.
PMID- 29344012
TI - Coding of Tissue and Cell Products.
PMID- 29344009
TI - Evaluation of nipple aspirate fluid as a diagnostic tool for early detection of
breast cancer.
AB - There has been tremendous progress in detection of breast cancer in
postmenopausal women, resulting in two-thirds of women surviving more than 20
years after treatment. However, breast cancer remains the leading cause of cancer
related deaths in premenopausal women. Breast cancer is increasing in younger
women due to changes in life-style as well as those at high risk as carriers of
mutations in high-penetrance genes. Premenopausal women with breast cancer are
more likely to be diagnosed with aggressive tumours and therefore have a lower
survival rate. Mammography plays an important role in detecting breast cancer in
postmenopausal women, but is considerably less sensitive in younger women.
Imaging techniques, such as contrast-enhanced MRI improve sensitivity, but as
with all imaging approaches, cannot differentiate between benign and malignant
growths. Hence, current well-established detection methods are falling short of
providing adequate safety, convenience, sensitivity and specificity for
premenopausal women on a global level, necessitating the exploration of new
methods. In order to detect and prevent the disease in high risk women as early
as possible, methods that require more frequent monitoring need to be developed.
The emergence of "omics" strategies over the last 20 years, enabling the
characterisation and understanding of breast cancer at the molecular level, are
providing the potential for long term, longitudinal monitoring of the disease.
Tissue and serum biomarkers for breast cancer stratification, diagnosis and
predictive outcome have emerged, but have not successfully translated into
clinical screening for early detection of the disease. The use of breast-specific
liquid biopsies, such as nipple aspirate fluid (NAF), a natural secretion
produced by breast epithelial cells, can be collected non-invasively for
biomarker profiling. As we move towards an age of active surveillance, home-based
liquid biopsy collection kits are increasingly being applied and these could
provide a paradigm shift where NAF biomarker profiling is used for routine breast
health monitoring. The current status of established and newly emerging imaging
techniques for early detection of breast cancer and the potential for alternative
biomarker screening of liquid biopsies, particularly those applied to high-risk,
premenopausal women, will be reviewed.
PMID- 29344011
TI - PCB118-Induced Cell Proliferation Mediated by Oxidative Stress and MAPK Signaling
Pathway in HELF Cells.
AB - The present study used human lung fibroblast (HELF) cells as a test model to
evaluate the role of oxidative stress (OS) and extracellular signal-regulated
kinases 1/2 (ERK1/2) protein in HELF cell proliferation exposed to PCB118.
Results from 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide
demonstrated that PCB118 at lower concentrations stimulated proliferation of HELF
cell and abrogate proliferative effect at higher dose concentrations and in a
time-dependent manner. Moreover, reactive oxygen species, malondialdehyde (MDA),
and superoxide dismutase showed a significant increase at higher concentrations
of PCB118 than the lower concentrations with the passage of time. Antioxidant
enzymes such as glutathione peroxidase exhibited decreasing trends in dose- and
time-dependent manner. Lipid peroxidation assay resulted in a significant
increase in MDA level in PCB118-treated HELF cells compared with controls,
suggesting that OS plays a key role in PCB118-induced toxicity. Comet assay
indicated a significant increase in genotoxicity at higher concentrations of
PCB118 exposure than the lower concentrations. It was found that PCB118 showed
expression of ERK1/2 protein after 4 hours, while after 48 hours, the protein
expression was less, indicating PCB toxicity to MAPK protein of HELF cell.
Oxidative stress, ERK1/2, and HELF cell proliferation exhibited correlation. The
results will elaborate toxicological evaluation of PCB118 to HELF cells and will
help to develop drug for PCB-induced diseases.
PMID- 29344013
TI - ISBT 128 Standard for Coding Medical Products of Human Origin.
AB - Background: ISBT 128 is an international standard for the terminology, coding,
labeling, and identification of medical products of human origin (MPHO). Full
implementation of ISBT 128 improves traceability, transparency, vigilance and
surveillance, and interoperability. Methods: ICCBBA maintains the ISBT 128
standard through the activities of a network of expert volunteers, including
representatives from professional scientific societies, governments and users, to
standardize and maintain MPHO identification. These individuals are organized
into Technical Advisory Groups and work within a structured framework as part of
a quality-controlled standards development process. Results: The extensive
involvement of international scientific and professional societies in the
development of the standard has ensured that ISBT 128 has gained widespread
recognition. The user community has developed confidence in the ability of the
standard to adapt to new developments in their fields of interest. The standard
is fully compatible with Single European Code requirements for tissues and cells
and is utilized by many European tissue establishments. ISBT 128's flexibility
and robustness has allowed for expansions into subject areas such as cellular
therapy, regenerative medicine, and tissue banking. Conclusion: ISBT 128 is the
internationally recognized standard for coding MPHO and has gained widespread use
globally throughout the past two decades.
PMID- 29344014
TI - From the EU Legislation to the Application of the Single European Code: Support
to the Implementation.
AB - The Italian National Transplant Centre (CNT) is coordinating with the Italian
National Blood Centre (CNS) the Joint Action '!' (www.eurocet128.eu), already
built the European Tissue Establishment and Tissue and Cell Product Compendia
between 2011 and 2014 in order to provide European Member States with a tool
which would grant traceability of tissues and cells at human transplant purpose
across the European Union. The two compendia are available on an online platform
hosted and managed by the European Commission.
PMID- 29344015
TI - Implementation of the Single European Code in a Multi-Tissue Bank.
AB - Introduction: The traceability of tissue and cells transplants is important to
ensure a high level of safety for the recipients. With the final introduction of
the Single European Code (SEC) in April 2017 in the EU a consistent system among
all member states became mandatory. Methods: The regulations for the SEC on EU
and national level were evaluated. An overview on the different parts of the SEC
with detailed explanations is given. Our own experiences with the implementation
of the SEC in our multi-tissue bank are reported in addition. Results: The
implementation of the SEC in our multi-tissue bank could be successfully
realized. However, it revealed a number of difficulties, especially the sterile
labeling of certain tissue transplants and the complex update of the existing
database. Conclusion: The introduction of the SEC has made a contribution to the
safety of recipients of tissue and cells transplants through a system of
comprehensive and transparent traceability.
PMID- 29344016
TI - Coding of Tissue and Cell Preparations Using Eurocode.
AB - Traceability of products requires their unique identification. In Germany blood
products have been encoded by Eurocode since 1998. EU Directives 2004/23/EC,
2006/86/EC and 2015/565/EC demanded unique identification and safe traceability
procedure also for tissues and cells. Eurocode IBLS e.V. and the German Society
of Transfusion Medicine and Immunohematology (DGTI) working parties '!' within
the Single European Code (SEC). Several data elements of Eurocode can be used to
create the complete SEC data structure, except the tissue establishment number.
This can be found on the EU Coding Platform in the internet. Consequently,
existing software and labeling solutions in Eurocode format could be easily
upgraded with SEC.
PMID- 29344017
TI - Global Registration Identifier for Donors (GRID) of Hematopoietic Stem Cells:
Road to Automation and Safety.
AB - Once a cohort exceeds a certain size, it becomes mandatory to assign an
identifier (ID) for each individual to ensure a secure, reliable, and unambiguous
assignment. In the field of hematopoietic stem cell transplantation, with a still
growing number of voluntary unrelated donors, it was recognized that a system
needs to be developed to uniquely identify potential donors on a global scale to
facilitate communication and to prevent errors in identification of donors.
Efforts in this respect resulted in establishment of the GRID, with a defined
structure and allocated rules. To successfully implement such a project,
collaboration among all organizations involved in the process of volunteer donor
recruitment, facilitation, and provision of hematopoietic stem cell products is
necessary. Therefore, rapidly accessible information combined with a high level
of communication and exchange of experiences is crucial. Established systems like
the ISBT 128 and the Single European Code (SEC), which standardize the
terminology, identification, coding, and labeling of tissues and cells of human
origin, serve as a basis on how to successfully implement the GRID on a global
scale.
PMID- 29344018
TI - Three-Year Experience in NAT Screening of Blood Donors for Transfusion
Transmitted Viruses in Croatia.
AB - Background: Croatia implemented individual donation (ID)-NAT testing of blood
donors in 2013 for three viruses HBV, HCV, and HIV-1 as a mandatory test for all
blood donors. This study assessed the impact of NAT screening 3 years after its
implementation. Methods: A total of 545,463 donations were collected and screened
for HBV, HCV, and HIV-1 using the Procleix Ultrio Plus Assay. All initially
reactive (IR) NAT samples were retested in triplicate and, if repeatedly reactive
(RR), NAT discriminatory assay (dNAT) was performed. ID-NAT positive donations
were confirmed by RT-PCR on the COBAS AmpliPrep/TaqMan platform. Results: Out of
545,463 samples tested, 108 (0.02%) were RR in NAT. There were 82 (75,9%) HBV
reactive, 16 (14.8%) HCV reactive, and 10 (9.3%) HIV-1 reactive samples. 51
(47.2%) samples were ID-NAT positive only. Out of these 51 NAT yield cases, 1
window period HIV-1 and 50 occult HBV infections (OBI) were determined. There
were only two potential HBV DNA transmissions from OBI donors. Conclusion: The
implementation of NAT screening for three viruses has improved blood safety in
Croatia. During the 3-year period, 1 window period HIV-1 and a number of occult
HBV donations were identified.
PMID- 29344019
TI - Using Blood Donor-Derived ABO and RhD Blood Groups Helps to Detect Wrong Blood in
Tube Errors in Recipients.
AB - Background: Comparing the ABO and RhD group of a recipient's current pre
transfusion sample against their historical group is an important means of
detecting wrong blood in tube (WBIT) errors. This study investigated the utility
of using the donor ABO and RhD group as the historical check for recipients.
Methods: A single database stores serological information on blood donors,
pregnant women, and patients throughout southern Denmark. A donor ABO and RhD
group can be the historical blood group should that donor later require a
transfusion. This database was searched to determine how often the ABO and RhD
group on a recipient's current pre-transfusion sample was discrepant with their
historical donor-derived blood group. Results: During about 21 years, ABO and RhD
groupings were performed on 76,455 blood donors and on 424,697 patients. There
were 13,630/424,697 (3.2%) patients who had their donor-derived ABO and RhD group
used as the historical comparison with the current sample; 6/13,630 (0.04%) of
the current pre-transfusion samples on these patients were discrepant with the
donor-derived historical group because of WBIT errors. Seven other discrepancies
with the donor-derived blood group were also found. Conclusion: Accessing the
donor-derived ABO and RhD group can be an important safeguard against WBIT
mediated mistransfusions.
PMID- 29344020
TI - A Case of Immune Thrombocytopenia as a Rare Side Effect of an Immunotherapy with
PD1-Blocking Agents for Metastatic Melanoma.
AB - Background: Checkpoint blocking agents such as pembrolizumab or nivolumab may
induce a diversity of mostly autoimmune-mediated side effects. These autoimmune
phenomena mainly affect ductless glands such as the pituitary gland
(hypophysitis), the thyroid gland (thyreoiditis), the skin (vitiligo and rash),
the colon (colitis), and the lung (pneumonitis). Furthermore, many other organs
or organ systems may be affected. Case Report: This work describes a case of an
immune thrombocytopenia that developed or rather became clinically significant
shortly after initiation of a systemic therapy with first nivolumab and later
pembrolizumab given due to metastatic melanoma. Platelet counts before this
systemic therapy were slightly decreased with values around 110/nl (normal value
140-400/nl). Thrombocytopenia developed or became apparent rapidly within 10 days
after the first intravenous application of nivolumab and worsened after
changeover to pembrolizumab. Therapy had to be stopped due to disease progression
and steady aggravation of thrombocytopenia. Immune hematology assays could prove
an autoimmune mediated genesis of thrombocytopenia. Conclusion: Checkpoint
inhibitors may induce a multiplicity of mostly autoimmune-mediated side effects.
In contrast to chemotherapy-induced cytopenia that results from bone marrow
toxicity, thrombocytopenia in melanoma patients treated with checkpoint
inhibiting substances seems to result from autoimmune-mediated side effects in
the majority of the cases. Thorough laboratory controls during these therapies
are therefore required. In case of thrombocytopenia, immune hematology testing to
diagnose or rule out immune thrombocytopenia is indispensable.
PMID- 29344021
TI - Relevance of Endothelial Cell-Specific Molecule 1 (Endocan) Plasma Levels for
Predicting Pulmonary Infection after Cardiac Surgery in Chronic Kidney Disease
Patients: The Endolung Pilot Study.
AB - Objectives: This pilot study aimed to evaluate the relevance of endocan plasma
levels for predicting pulmonary infection after cardiac surgery in patients with
chronic kidney disease (CKD). Methods: Serum collected in a previous prospective
cohort study (from 166 patients with preoperative CKD who underwent cardiac
surgery) was used. Five patients with postoperative pulmonary infection were
compared with 15 randomly selected CKD patients with an uneventful outcome. Blood
samples were tested at 4 time points (preoperatively and 6, 12, and 24 h after
the end of surgery). Endocan, procalcitonin, and C-reactive protein plasma levels
were compared between the two groups. Results: At 6 h, the patients with
pulmonary infection had significantly higher levels of endocan than the patients
without pulmonary infection (24.2 +/- 15.6 vs. 6.4 +/- 3.2 ng/mL; p = 0.03). A
receiver operating characteristic curve analysis showed 80% sensitivity and 100%
specificity for endocan to predict pulmonary infection (area under the curve
0.84), with a cutoff value of 15.9 ng/mL. The time saved by assessment of the
endocan dosage compared to a clinical diagnosis of pulmonary infection was 47 h.
Conclusion: This pilot study showed that a specific study to assess the link
between endocan plasma levels and pulmonary infection after cardiac surgery in
CKD patients is of potential utility.
PMID- 29344022
TI - Role of Body Mass Index in Acute Kidney Injury Patients after Cardiac Surgery.
AB - Background/Aims: To explore the association of body mass index (BMI) with the
risk of developing acute kidney injury after cardiac surgery (CS-AKI) and for AKI
requiring renal replacement therapy (AKI-RRT) after cardiac surgery. Methods:
Clinical data of 8,455 patients undergoing cardiac surgery, including demographic
preoperative, intraoperative, and postoperative data were collected. Patients
were divided into underweight (BMI <18.5), normal weight (18.5<= BMI <24),
overweight (24<= BMI <28), and obese (BMI >=28) groups. The influence of BMI on
CS-AKI incidence, duration of hospital, and intensive care unit (ICU) stays as
well as AKI-related mortality was analyzed. Results: The mean age of the patients
was 53.2 +/- 13.9 years. The overall CS-AKI incidence was 33.8% (n = 2,855) with
a hospital mortality of 5.4% (n = 154). The incidence of AKI-RRT was 5.2% (n =
148) with a mortality of 54.1% (n = 80). For underweight, normal weight,
overweight, and obese cardiac surgery patients, the AKI incidences were 29.9,
31.0, 36.5, and 46.0%, respectively (p < 0.001). The hospital mortality of AKI
patients in the 4 groups was 9.5, 6.0, 3.8, and 4.3%, whereas the hospital
mortality of AKI-RRT patients in the 4 groups was 69.2, 60.8, 36.4, and 58.8%,
both significantly different (p < 0.05). Hospital and ICU stay durations were not
significantly different in the 4 BMI groups. Conclusion: The hospital prognosis
of AKI and AKI-RRT patients after cardiac surgery was best when their BMI was in
the 24-28 range.
PMID- 29344023
TI - Eicosapentaenoic Acid as a Potential Therapeutic Approach to Reduce
Cardiovascular Risk in Patients with End-Stage Renal Disease on Hemodialysis: A
Review.
AB - Background: Patients with end-stage renal disease on hemodialysis have excess
cardiovascular disease (CVD) burden with substantially increased CV event rates
compared with the general population. Summary: Traditional interventions that,
according to standard clinical guidelines, reduce CV risk such as
antihypertensive therapy, diet, exercise, and statins are not similarly effective
in the hemodialysis population. This raises the question of whether additional
risk factors, such as enhanced inflammation and oxidative stress, may drive the
increased CVD burden in hemodialysis patients. Eicosapentaenoic acid (EPA), an
omega-3 polyunsaturated fatty acid, is incorporated into the atherosclerotic
plaque as well as membrane phospholipid bilayers and produces beneficial effects
on inflammatory and oxidative mechanisms involved in atherosclerotic plaque
formation and progression. EPA levels and the ratio of EPA to the omega-6
polyunsaturated fatty acid arachidonic acid (AA) are reduced in hemodialysis
patients. Serum EPA levels have been inversely correlated with proinflammatory
cytokines, and the EPA/AA ratio has been inversely associated with CV events in
hemodialysis cohorts. Three recent studies involving over 800 hemodialysis
patients and follow-up of 2-3 years suggest that EPA therapy may improve clinical
outcomes in this patient population as evidenced by significant reductions in
cardiovascular mortality, all-cause mortality, and/or CV events. Key Messages:
Further studies with high-purity EPA are warranted in patients on hemodialysis,
especially given the fact that other interventions including antihypertensives,
diet, exercise, and statins have not provided meaningful benefit.
PMID- 29344024
TI - Elevated Phosphate Levels Trigger Autophagy-Mediated Cellular Apoptosis in H9c2
Cardiomyoblasts.
AB - BACKGROUND/AIM: In chronic kidney disease (CKD), kidneys fail to maintain
phosphorus homeostasis in serum. Elevated phosphorus levels in serum have been
associated with cardiovascular diseases in CKD patients and in normal
individuals. In this study, we evaluated the level of autophagy- and apoptosis
related markers under different concentrations of hyperphosphate in myocardial
cells. METHODS: Modulation inflicted on the levels of various survival-,
autophagy-, and apoptosis-related markers were determined by Western blotting
analysis using total protein extract. FITC-annexin V staining was performed to
quantify the apoptotic cells in all groups. RESULTS: Hyperphosphate treatments
showed to induce autophagy-related proteins beclin-1, ATG7, and LC3 II through
the pAMPK-ULK1 pathway in Western blotting analysis. Further, apoptosis
associated proteins such as Bax, Bid, cytochrome c, and c-caspase-9 were also
upregulated with hyperphosphate treatment. 3-Methyladenine, an autophagy
inhibitor, inhibited apoptosis significantly in FITC-annexin V staining, and the
inhibition of Bax, cytochrome c, and c-caspase-3 was shown by Western blotting.
CONCLUSION: The results suggest that hyperphosphate in H9c2 cardiomyoblasts would
lead to cellular apoptosis via autophagy, which is mediated by the pAMPK
signaling pathway. Our findings revealed the possible mechanism responsible for
the heart damage under hyperphosphatemia.
PMID- 29344025
TI - Insulin Resistance in Kidney Disease: Is There a Distinct Role Separate from That
of Diabetes or Obesity?
AB - Insulin resistance is a central component of the metabolic dysregulation observed
in obesity, which puts one at risk for the development of type 2 diabetes and
complications related to diabetes such as chronic kidney disease. Insulin
resistance and compensatory hyperinsulinemia place one at risk for other risk
factors such as dyslipidemia, hypertension, and proteinuria, e.g., development of
kidney disease. Our traditional view of insulin actions focuses on insulin
sensitive tissues such as skeletal muscle, liver, adipose tissue, and the
pancreas. However, insulin also has distinct actions in kidney tissue that
regulate growth, hypertrophy, as well as microcirculatory and fibrotic pathways
which, in turn, impact glomerular filtration, including that governed by
tubuloglomerular feedback. However, it is often difficult to discern the distinct
effects of excess circulating insulin and impaired insulin actions, as exist in
the insulin resistance individual, from the associated effects of obesity or
elevated systolic blood pressure on the development and progression of kidney
disease over time. Therefore, we review the experimental and clinical evidence
for the distinct impact of insulin resistance on kidney function and disease.
PMID- 29344026
TI - Evaluation of the Predictive Value of the Serum Calcium-Magnesium Ratio for All
Cause and Cardiovascular Mortality in Incident Dialysis Patients.
AB - Background/Aim: Cardiovascular disease is the most serious cause of death in
patients on hemodialysis. Low serum magnesium (Mg) and high serum calcium (Ca)
levels have been associated with poor outcome and cardiovascular mortality in
patients on maintenance and initiation dialysis. As a more accurate marker is
warranted, we evaluated the efficacy of a novel serum Ca-Mg marker of all-cause
and cardiovascular mortality that indicates vessel calcification. Methods: We
recruited 378 consecutive patients with end-stage renal disease who started
dialysis between January 2009 and December 2015 at the Japanese Red Cross
Ishinomaki Hospital. We collected data of patients' demographic characteristics
and comorbidities from their electronic medical records. We retrospectively
examined the association of the serum Ca-Mg ratio with all-cause and
cardiovascular mortality using the Cox proportional hazard model, and determined
the value that predicted cardiovascular death using the receiver operating
characteristic (ROC) curve. Results: Overall, 253 patients with serum Mg and Ca
data were analyzed. The 3-year survival rate of this group was 0.70 (95%
confidence interval [CI] 0.55-0.80), and the hazard ratio for the risk of death
was 3.94 (95% CI 1.37-11.31). The 3-year cardiovascular mortality rate was 0.12
(95% CI 0.05-0.23), which was significantly higher than that of the other groups.
The ROC curve of cardiovascular mortality with the Ca-Mg ratio was greater than
that of Mg (area under the curve 0.75 vs. 0.69, p = 0.037). Conclusion: A high Ca
Mg ratio was significantly associated with all-cause and cardiovascular
mortality, and it was more accurate than serum Mg.
PMID- 29344027
TI - Plasma Volume and Renal Function Predict Six-Month Survival after Hospitalization
for Acute Decompensated Heart Failure.
AB - Background: Plasma volume (PV) is contracted in stable patients with heart
failure (HF) due to decongestion strategies. On the other hand, increased PV can
adversely affect the trajectory of HF. We therefore examined the effects of
increased percentage change in PV (%DeltaPV), blood urea nitrogen (BUN), and
%DeltaPV stratified by BUN and glomerular filtration rate (GFR) on survival after
discharge in patients hospitalized for acute decompensated HF (ADHF). Methods: We
used the Strauss-Davis-Rosenbaum formula to calculate the %DeltaPV between
baseline and hospital discharge in a cohort from the Evaluation Study of
Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial
(ESCAPE). Kaplan-Meier curves were constructed for survival over 6 months. Cox
proportional hazards regression was used to obtain adjusted hazard ratios (HR)
and 95% confidence intervals (95% CI) for the associations between survival after
discharge and %DeltaPV, BUN, and %DeltaPV stratified by BUN and GFR. Results: Of
the 324 patients included in our study (age 56.1 +/- 13.6 years, 26.5% female),
those with increased or no %DeltaPV at discharge were less likely to survive at 6
months compared with those having reduced %DeltaPV (log rank, p = 0.0093).
Increased %DeltaPV (HR 1.08 per 10% increase; 95% CI: 1.02-1.14) and increased
BUN at discharge (HR 1.02 per mg/dL; 95% CI: 1.01-1.03) were independently
associated with worse survival. Decreasing %DeltaPV had a greater association
with improved survival in patients with discharge BUN <31 mg/dL (p = 0.02) and
discharge GFR >40 mL/min/1.73 m2 (p = 0.047). Conclusions: Increased %DeltaPV and
BUN at discharge predicted worse 6-month survival in patients with ADHF.
Decreased %DeltaPV with low BUN or high GFR at discharge was associated with
improved survival.
PMID- 29344028
TI - Combination Therapy with Renin-Angiotensin System Blockers and Vitamin D Receptor
Activators for Predialysis Patients Is Associated with the Incidence of
Cardiovascular Events after Dialysis Initiation: A Multicenter Nonrandomized
Prospective Cohort Study.
AB - Background: Several human studies reported that the combined use of renin
angiotensin system blockers (RASBs) and vitamin D receptor activators (VDRAs)
resulted in decreased urinary protein excretion. However, it is unknown whether
this combination therapy influences the incidence of cardiovascular (CV) events
in dialysis patients. Methods: The study was a multicenter nonrandomized
prospective cohort analysis including 1,518 patients. Patients were classified
into 4 groups based on medications prescribed before dialysis initiation: those
who did not receive RASBs or oral VDRAs (N group), those receiving only RASBs,
those receiving only VDRAs, and those receiving a combination of RASBs and VDRAs
(RD group). CV events after dialysis initiation were compared using the log-rank
test. Factors contributing to the incidence of CV events were examined using
multivariate Cox proportional hazard regression analysis. Results: Significant
differences were observed in the incidence of CV events and all-cause mortality
between the 4 groups (p = 0.021 and p = 0.001, respectively). Cox proportional
hazard analysis revealed that the incidence of CV events was significantly lower
in the RD group than in the N group (hazard ratio [HR] = 0.65, 95% confidence
interval [CI]: 0.50-0.86, p = 0.002). Multivariate analysis revealed that the
incidence of CV events was significantly lower in the RD group than in the N
group (HR = 0.66, 95% CI: 0.47-0.93, p = 0.016). Conclusion: Combination therapy
with RASBs and VDRAs in patients before dialysis initiation was associated with a
reduction in CV events during maintenance dialysis.
PMID- 29344029
TI - Primary Adrenal Lymphoma Presenting with Adrenal Failure: A Case Report and
Review of the Literature.
AB - Introduction: Primary adrenal lymphoma is rare, with a few cases reported in the
literature. Most often it manifests as bilateral adrenal lesions and adrenal
insufficiency is a common complication. Case Presentation: A 53-year-old male was
referred with abdominal discomfort and darkening of the skin since 1 month prior
to admission. His workups detected large bilateral adrenal masses. The patient
was admitted due to hypotension, and was diagnosed with adrenal insufficiency.
Laboratory studies showed high erythrocyte sedimentation rate (ESR), lactate
dehydrogenase (LDH), and adrenocorticotropin levels. There was no other organ
involvement and computed tomography (CT)-guided percutaneous biopsy of the
adrenal gland revealed B-cell type of non-Hodgkin lymphoma. Replacement therapy
with glucocorticoid and mineralocorticoid was initiated with remission of
symptoms. After 3 months of chemotherapy his condition improved, but the patient
worsened thereafter and died 2 months later. Conclusions: However, this case
reminded the importance of considering primary adrenal lymphoma in the
differential diagnosis of bilateral adrenal masses, especially if the patient
presents with adrenal insufficiency.
PMID- 29344030
TI - Optimal Cutoff Points for Anthropometric Variables to Predict Insulin Resistance
in Polycystic Ovary Syndrome.
AB - Background: Insulin resistance (IR) is a major cardiometabolic risk factor in
females with polycystic ovary syndrome (PCOS). The euglycemic clamp is the gold
standard method to measure IR. However, considering the time and cost that it
takes, surrogate markers of IR are now widely used. The current study aimed at
evaluating the cutoff points of even less invasive anthropometric and body
composition variables to predict IR in females with PCOS. Methods: The current
cross sectional study selected 224 females with PCOS, using Rotterdam criteria,
referred to reproductive endocrinology research center; 88 of which were
diagnosed with insulin resistance. Receiver operating characteristics curve was
used to explore the best cutoff values of each anthropometric and body
composition measures. IR was defined as homeostasis model assessment formula
greater or equal to 2.6: HOMA-IR = fasting insulin (mU/L) * fasting plasma
glucose (mM/L)/22.5. Results: The highest area under the curve (0.751) was for
the multiplication of waist circumference (WC) by body mass index (BMI), as a
single index. The highest sensitivity and specificity were for body water (BW)
percentage (82% for values greater than 32.85%) and WC (79% for values greater
than 88 cm), respectively. Conclusions: It was concluded that there were simple
anthropometric variables; e.g., WC * BMI, percentage of BW, and WC that could
help to estimate IR in clinical settings especially when the gold standard or
surrogate markers of IR were unavailable.
PMID- 29344031
TI - Age-Period-Cohort Analysis of Obesity and Overweight in Iranian Children and
Adolescents.
AB - Background: To date, few studies looked upon obesity and overweight in children
and adolescents through the 3 different temporal dimensions of age, period, and
cohort. The current study aimed at evaluating the trends of these health issues
among children under 19 years old using the age-period-cohort (APC) analysis.
Methods: Data gathered through 5 cross sectional studies including 2 national
health surveillance (1990 - 91 and 1999), and 3 CASPIAN surveys (2003, 2009, and
2011). Subjects were classified by their body mass index (BMI) into 3 groups of
normal (BMI < 85th percentile), overweight-obese (85th percentile < BMI < 95th
percentile), and obese (95th percentile < BMI). Intrinsic estimator method was
used to analyze the effects of age, period, and birth cohort on obesity and
overweight among the subjects. Results: A total of 80,698 children and
adolescents under 19 years old, including 40,419 (50.09%) males and 40,279
(49.91%) females, were evaluated. The prevalence of obesity decreased
progressively by age in males and females with minor discrepancies. It increased
from 1990 to 2009 in both genders, but from that point on remained quite constant
in males and dropped significantly in females. The prevalence of obesity was
steady in earlier birth cohorts, but increased significantly after the birth
cohorts from 1986 to 1990. Conclusions: Environmental factors and social stresses
during neonatal and infantile periods (birth cohort effect) along with other
variables influencing the children later in their lives (period effect) affect
the prevalence of overweight and obesity substantially. Moreover, a decrease in
the prevalence of obesity and overweight was observed by age increase (age
effect).
PMID- 29344032
TI - Neck Circumference Percentiles of Iranian Children and Adolescents: The Weight
Disorders Survey of CASPIAN IV Study.
AB - Background: Neck circumference (NC), emerging as a key morphological index for
pediatric obesity, is associated with obesity- and overweight-related detrimental
conditions in children. In this study, we aimed to provide the age- and sex
specific percentile reference values for neck circumference of the Iranian
children and adolescents. Methods: We used the data gathered through the weight
disorders survey of CASPIAN IV study conducted in 2011 - 2012 in Iran, including
a total of 21954 Iranian children and adolescents, composed of 10750 girls and
11204 boys, aged 7 - 18 years old. We presented the interval of NC percentile in
three age groups of 7 - 10 years, 11 - 14 years, and 15 - 18 years. Finally, age
specific nomograms of NC for both genders in the Iranian and Canadian populations
were compared. Results: The intervals of 90th percentile of NC for boys in the
three periods of school age (7 - 10 years), pre-adolescence (11 - 14 years), and
adolescence (15 - 18 years) were 24.2 - 30.0 cm, 26.6 - 33.2 cm, and 30.1 - 38.5
cm, respectively. These intervals for girls were 23.7 - 30.1 cm, 26.5 - 33.7 cm,
and 28.5 - 36.0 cm, respectively. NC increased with age in both boys and girls
and its variability showed an increasing trend with age. Conclusions: We
demonstrated for the first time the NC reference values for the Iranian children
and adolescents aged 7 - 18 years old. Considering the significant differences
between our national NC references and the values reported from the Canadian
population, it seems logical to use these national percentiles not only for
epidemiologic studies but also for routine clinical examinations.
PMID- 29344033
TI - Investigating the Prevalence of Low Bone Mass in Children of Southern Iran and
Its Associated Factors.
AB - Background: Improving peak bone mass and bone strength in the first years of life
and enhancing it during young adulthood could prevent osteoporosis and fractures
in the last years of life. We evaluated the prevalence of low bone mass in the
lumbar and femoral neck and its associated factors in southern Iranian children.
Methods: This is a cross-sectional study on healthy Iranian children aged 9 - 18
years old during 2011 - 2012. Dual energy X-ray absorptiometry (DEXA) was used
for measuring bone mineral density (BMD). BMD Z-score <= -2 was considered as
low. Anthropometric data, physical activity, sun exposure, puberty, and mineral
biochemical parameters were assessed. Data were analyzed using SPSS v.15.
Results: 477 normal children, including 236 (49.5%) girls and 241 (50.5%) boys,
aged 13.8 +/- 2.7 years were enrolled. Prevalence of low bone mass (LBM) in the
femoral and lumbar region was 10.7% and 18.7%, respectively. The prevalence of
LBM in femur of girls is twice more than boys. Fat mass index, BMI Z-score, and
physical activity were associated with lumbar low bone mass. BMI Z-score and
physical activity were associated with femoral low bone mass. Conclusions: High
prevalence of low bone mineral density in children 9 to 18 years in south of the
country is concerned and is needed to plan for prevention and treatment. BMI-Z
score, fat mass index, and physical activity were the 3 most important preventive
factors in developing low bone mass in children.
PMID- 29344034
TI - Socio-Demographic Determinants of Health-Related Quality of Life in Tehran Lipid
and Glucose Study (TLGS).
AB - Background: Health-related quality of life (HRQOL) is a multi-dimensional concept
that is affected by different variables. A large body of evidence shows that
socio-demographic factors have a significant influence on HRQOL. When considering
differences in cultural contexts and social values of various countries and the
lack of evidence regarding socio-demographic determinants of HRQOL among the
Iranian general population, it is important to verify the main socio-demographic
determinants of HRQOL in an urban Iranian population. Objectives: This study
aimed to explore socio-demographic factors associated with HRQOL and to ascertain
the determinants of poor HRQOL in participants of the Tehran lipid and glucose
study (TLGS). Methods: The participants included 3491 adults, aged >= 20 years,
who had participated in the TLGS. To obtain socio-demographic and HRQOL
information, participants were interviewed by trained interviewers. Mean HRQOL
scores were compared using the student's t test and analysis of variance (ANOVA).
To determine significant determinants of poor HRQOL, multivariate logistic
regression analysis was performed. Results: Mean ages of males and females were
47.7 +/- 15.6 and 47.8 +/- 14.2 years, respectively and 58.6% of participants
were male. Males had significantly higher scores compared to females in both the
physical and mental domains of HRQOL (P < 0.001). In males, significant
determinants of poor physical HRQOL were older age, being married, being
unemployed yet having other sources of income, having literacy levels below high
school diploma, and having chronic diseases (P < 0.05). In females, however older
age and being housewives were significant determinants of poor physical HRQOL (P
< 0.05). In addition, significant determinants of poor mental HRQOL were younger
age and being single or divorced/widowed in males and younger age and being
illiterate as well as having literacy levels below high school diploma in females
(P < 0.05). Conclusions: Current findings highlight the importance of socio
demographic determinants of HRQOL in both genders, specifically in the physical
domain, and demonstrate their roles to be more prominent in males. These findings
highlight gender-specific associations between socio-demographic factors and
various aspects of HRQOL among the TLGS population, which could be applied in
future research focusing on non-communicable diseases and planning health
promotion programs.
PMID- 29344035
TI - Hypercalcaemic Pancreatitis, Adrenal Insufficiency, Autoimmune Thyroiditis and
Diabetes Mellitus in a girl with Probable Sarcoidosis.
AB - Introduction: Sarcoidosis is a multisystemic granulomatous disease with diverse
and often non-specific symptoms during childhood. The clinical manifestations
sometimes include endocrinopathies related to sarcoid infiltration of various
endocrine organs, but more commonly due to the associated autoimmune endocrine
disorders. There are only a few reports of multiple autoimmune and non-autoimmune
endocrine problems occurring simultaneously in patients with sarcoidosis. We
report a girl with probable sarcoidosis who also had Hashimoto's thyroiditis,
Type 1 diabetes (T1D) and secondary adrenal insufficiency. Case Presentation: A 9
year-old girl previously diagnosed with autoimmune hypothyroidism and vitamin D
deficiency, presented with hypercalcemic pancreatitis after initiating vitamin D
supplementation that lead to a diagnosis of probable sarcoidosis. Secondary
adrenal insufficiency and T1D were subsequently diagnosed. Her angiotensin
converting enzyme levels on 2 occasions were 106 and 135 nmol/mL/min (normal
range 10 - 43). All investigations conducted to exclude several infectious and
malignant conditions that may mimic sarcoidosis were negative. The patient showed
a good response to treatment with hydrocortisone, levothyroxine, insulin and
methotrexate. Conclusions: To our knowledge, ours is the youngest ever patient
reported in the literature with sarcoidosis to develop multiple autoimmune and
non-autoimmune endocrinopathies.
PMID- 29344037
TI - The Effects of Ginger on Fasting Blood Sugar, Hemoglobin A1c, and Lipid Profiles
in Patients with Type 2 Diabetes.
AB - Background: Lipid and glycemic abnormalities are prevalent in diabetes leading to
long term complications. Use of safe and natural foods instead of medications is
now considered by many scientists. Objectives: This study aimed at determining
the effect of ginger on lipid and glucose levels of patients with type 2 diabetes
mellitus. Methods: In a double-blind placebo-controlled trial, 50 patients with
type 2 diabetes were randomly allocated to 2 groups of intervention (n = 25) and
placebo (n = 25). Each patient received 2000 mg per day of ginger supplements or
placebo for 10 weeks. Serum levels of fasting blood sugar (FBS), total
cholesterol (TC), triacylglycerol (TG), low density lipoprotein cholesterol (LDL
C), high density lipoprotein cholesterol (HDL-C), and glycosylated hemoglobin
(HbA1C) were analyzed. Daily dietary intakes and anthropometric parameters were
also determined. Results: Data from 45 patients were analyzed (23 patients in the
ginger group and 22 patients in the control group) at the end of the study.
Ginger consumption significantly reduced serum levels of fasting blood glucose (
26.30 +/- 35.27 vs. 11.91 +/- 38.58 mg/dl; P = 0.001) and hemoglobin A1C (-0.38
+/- 0.35 vs. 0.22 +/- 0.29 %; P < 0.0001) compared to the placebo group. Ginger
consumption also reduced the ratio of LDL-C/HDL-C (2.64 +/- 0.85 vs. 2.35 +/-
0.8; P = 0.009). However, there was no significant change in serum concentrations
of triglycerides, total cholesterol, LDL-C, and HDL-C due to the ginger
supplements. Conclusions: The current results showed that ginger could reduce
serum levels of fasting blood glucose and hemoglobin A1C in patients with
diabetes.
PMID- 29344036
TI - Primordial and Primary Preventions of Thyroid Disease.
AB - Background: Primordial and primary preventions of thyroid diseases are concerned
with avoiding the appearance of risk factors, delaying the progression to overt
disease, and minimizing the impact of illness. Summary: Using related key words,
446 articles related to primordial and primary, preventions of thyroid diseases
published between 2001-2015 were evaluated, categorized and analyzed. Prevention
and elimination of iodine deficiency are major steps that have been successfully
achieved and maintained in many countries of the world in last 2 decades. Recent
investigations related to the effect of cigarette smoking, alcohol consumption,
and autoimmunity in the prevention of thyroid disorders have been reviewed.
Conclusions: The cornerstone for successful prevention of thyroid disease entails
timely implementation of its primordial and primary preventions, which must be
highly prioritized in related health strategies by health authorities.
PMID- 29344038
TI - An Evaluation of Acupressure on the Sanyinjiao (SP6) and Hugo (LI4) Points on the
Pain Severity and Length of Labor: A Systematic Review and Meta-analysis Study.
AB - Background: In this study, the effects of SP6 and LI4 acupressure on the pain
severity and length of labor are examined. Materials and Methods: This systematic
review and meta-analysis study was performed on articles published in 2004-2015.
The articles, published in the English and Farsi languages, related to the
effects of acupressure on the SP6 and LI4 points on the length and pain severity
of labor. Data were collected by searching medical databases, including PubMed,
ISI, MagIran, Google Scholar, Iran Medex, SID, Irandoc, and EMBASE, for relevant
material. Results: Women who received SP6 acupressure experienced less pain
immediately after the intervention [-0.56, 95% confidence interval (CI): -0.77,
0.36] than women in the touch group and exhibited decrease in the length of labor
(-0.99, 95% CI: -1.39, -0.39), the active phase (0.95, 95% CI: -1.30, -0.61), and
the second stage of labor (-0.39, 95% CI: -0.74, -0.03). Women who received LI4
acupressure experienced less pain immediately after the intervention (-0.94, 95%,
CI: -1.36, -0.53) than women in the touch group and exhibited shorter active
phase (-0.91, 95%, CI: -1.18, -0.63) and second stage of labor (-0.55, 95%, CI:
0.95, -0.15) lengths. Conclusions: The use of SP6 and LI4 acupressure shows
promise as a method for managing the length and pain severity of labor, but
further study is required to establish its effectiveness along with other
pharmacological and nonpharmacological methods.
PMID- 29344039
TI - The Effect of Auriculotherapy on the Stress and the Outcomes of Assistant
Reproductive Technologies in Infertile Women.
AB - Background: Infertility means failure to achieve pregnancy after one year of
regular unprotected sexual intercourse. Infertile women may experience severe
stress and depression. Numerous studies have indicated that auriculotherapy could
reduce stress. Thus, the aim of the present study was to determine the effect of
auriculotherapy on the stress and the outcome assisted reproductive technology in
infertile women. Materials and Methods: The present study was a clinical trial
that was conducted on 56 infertile women aged 20-45, who were assigned into two
groups of intervention and control, from November 2014 to November 2015. The
control group only received the routine treatments, while the intervention group,
in addition to their routine treatment, received auriculotherapy for 8-10
sessions during menstrual cycle. Both groups completed Newton's Fertility Problem
Inventory in three stages. The datasets collected for the study were analyzed
using independent t-test, repeated-measures analysis of variance, and Chi-square
test. Results: The mean score of stress in the intervention group decreased
significantly, compared to the control group prior to the embryo transfer and
pregnancy test stages. Although insignificant, the rate of pregnancy in the
intervention group was higher than the control group. There was a significant
increase in the rate of clinical pregnancy in the intervention group, compared to
the control. Conclusions: The results indicated that auriculotherapy might be
effective in reducing stress and improving the outcome of assisted reproductive
treatment.
PMID- 29344040
TI - Health Journalism: Health Reporting Status and Challenges.
AB - Background: Media play crucial role in disseminating health information. Due to
the importance of accurate health news reports, and the national need to
professionalism in health journalism, this study aimed to investigate the
characteristics of health journalists, and health reporting status and the
challenges involved. Materials and Methods: Using consensus sampling, this
descriptive cross-sectional study was conducted on all health news reporters in
Isfahan (34 journalists) in 2015-2016. Data collection was done via a researcher
made questionnaire. Content validity of the questionnaire was determined by
qualitative method and based on the opinions of six experts. The test-retest
reliability coefficient was 98.0. Data analysis was done by Statistical Package
for the Social Sciences, version 16 and descriptive statistics and content
analysis were used for analyzing the responses to two open questions. Results:
Among 34 journalists, 56% were women and 44% men; the majority of journalists
(65%) had no specialized training on health reporting, 35% of journalists were
not able to understand the health issues, and the knowledge of medical
terminology in 59% of them was moderate to low. The most important required skill
for reporters was the ability to interpret medical research reports (88%), 97%
were eager to participate in specialized health education. Conclusions: Our study
showed that health journalists lacked knowledge and specialized training for
dissemination of health news. This has brought about serious challenges. Thus,
development and implementation of training courses in close collaboration with
educational department of the Ministry of Health and news programs professionals
at Islamic Republic of Iran Broadcasting is highly recommended.
PMID- 29344041
TI - Impact of Nutrition Education in Improving Dietary Pattern During Pregnancy Based
on Pender's Health Promotion Model: A Randomized Clinical Trial.
AB - Background: Different types of nutrients in adequate amounts are required to meet
the increased demands of the mother and the developing fetus. Therefore, we
examined the impact of nutrition education on the number of food servings per
day. Materials and Methods: Pregnant mothers were recruited to a prospective,
randomized clinical trial from May to September, 2016. At 6-10 weeks of
gestation, the participants were randomly divided into the intervention (n = 96)
or the control group (n = 96), and were followed-up until the end of pregnancy.
Each woman in the experimental group met the study nutritionist at the time of
enrollment and an individualized nutrition plan was developed. In addition, the
nutrition education based on Pender's Health Promotion Model (HPM) was designed,
including three 45-60 min training sessions in 6-10, 18, and 26 weeks of
pregnancy. The participants' usual food intake using a three-day dietary record
was assessed at 6-10 weeks and 34-36 weeks of gestation. Results: The mean scores
of the perceived benefits, self-efficacy, activity-related affect, interpersonal
influences (husband support), and commitment to action increased while the
competing demand scores decreased in the interventional group compared with the
control group. The mean standard deviation (SD) of food portions from grain
[10.40 (1.96) versus 12.70 (1.93) in the control group], vegetable [3.88 (1.33)
versus 2.96 (0.91)], fruit [4.02 (0.05) versus 3.95 (0.91)], dairy [2.33 (0.68)
versus 2.11 (0.45)], and meat [3.17 (0.68) versus 2.96 (0.67)] were improved in
the experimental group. Conclusions: Pender's HPM for nutrition education is
effective based on the compliance of pregnant women to the dietary guideline and
the food guide pyramid.
PMID- 29344042
TI - Effect of Telephone Follow-up by Nurses on Self-care in Children with Diabetes.
AB - Background: Diabetes is a serious chronic disease during childhood. Because of
the chronic nature of the disease, self-care is necessary. Education alone is not
effective in providing care. Misunderstanding by the patients regarding diabetes
during the training programs render telephone follow-up after training essential.
Materials and Methods: This quasi-experimental study with two groups
(experimental and control) was conducted in two phases in 2014. The study
population consisted of 70 children of 10-18 years of age with type I diabetes
(35 patients in the experimental group and 35 in the control group). The
participants were randomly selected from the patients referring to the Sedigheh
Tahereh Diabetic Research and Treatment Center in Isfahan, Iran. Data were
collected using a researcher-made questionnaire on self-care and a glycosylated
hemoglobin recording form. The experimental group received 12 weeks of telephone
follow-up training by the center, whereas the control group received no follow
up. Results: The results showed that, after intervention, the total mean score of
self-care in all aspects of diabetes care for children was significantly higher
in the experimental group (p < 0.001). In addition, a statistically significant
difference was observed between the experimental and control groups in terms of
mean glycosylated hemoglobin after the intervention (p = 0.030). Conclusions: It
can be concluded that telephone follow-up by a nurse can improve total self-care
and glycosylated hemoglobin in patients with type I diabetes.
PMID- 29344043
TI - Assessment of the Midwifery Students' Clinical Competency Before Internship
Program in the Field Based on the Objective Structured Clinical Examination.
AB - Background: One of the important goals of clinical education is to promote the
level of students' clinical skills. About 50% of the midwifery education is
focused on clinical education, which has a great importance in shaping the
professional skills of the students. The aim of this study was to determine the
ability of students in some practical skills, before internship program in the
field, using objective structured clinical examination (OSCE). Materials and
Methods: This research was a descriptive cross-sectional study with a single
stage, multivariate prospective design. Twenty-seven midwifery students from the
Isfahan University of Medical Sciences who were in their sixth semester were
selected by convenience sampling during the second semester of 2015-2016
educational year. OSCE was executed at skill laboratories in 8 stations during
one day, and researcher-made checklists were used; their content and face
validity were approved and their reliability was confirmed by a Cronbach's alpha
coefficient of 0.97. Data analysis was performed by SPSS19. Results: Results
showed that the level of students' skills at pelvic exam station was 39.97%, at
bladder catheterization was 66.92%, at Leopold was 42.7%, at fetal ECG
interpretation was 50.49%, at physical examination was 21.30%, at fetal
resuscitation was 48.81%, at breast examination was 56.32%, and at answering the
questions was 23.49%. Conclusions: Results show that students gained a score of
less than 50% in most skills. Therefore, they are not efficiently skilled for
these essential clinical skills. Nonetheless, these procedures need the minimum
skills that are required from students after graduation and before entering the
working environment in hospitals and health centers. Therefore, more attention
should be paid to these skills while planning internship programs before students
enter the field. Also, more attention is required while teachers teach these
skills and students are supposed to regard their weaknesses in these skills.
PMID- 29344044
TI - Ethical Challenges of Embryo Donation in Embryo Donors and Recipients.
AB - Background: Embryo donation, as one of the novel assisted reproductive
technologies (ART), has remained a controversial issue. This is due to this
methods' need for individuals from outside the family circle. Their presence can
cause many ethical issues and complicate the designing and planning of the embryo
donation process. The present study was conducted with the aim to assess the
ethical challenges of embryo donation from the view point of embryo donors and
recipients. Material and Methods: This descriptive, cross-sectional study was
conducted on 192 couples (96 embryo donators and 96 embryo recipients) referring
to Isfahan Fertility and Infertility Center and Royan Institute, Iran. The
subjects were selected through convenience sampling. The data collection tool was
the researcher-made Ethical Challenges Questionnaire. Data were analyzed in SPSS
software. Results: Embryo donors and recipients expresses the most important
ethical challenges of embryo donation in the principle of justice (70.20%) and
respect for autonomy (42.57%), respectively. Conclusions: The four ethical
principles are important in the view of embryo donors and recipients; however,
they highlighted the importance of the principle of respect for autonomy
considering the existing barriers in the services of infertility centers.
Legislators and relevant authorities must take measures toward the development of
guidelines for this treatment method in the framework of ethics principles and
incorporate all four principles independently.
PMID- 29344045
TI - Predicting Nurses' Psychological Safety Based on the Forgiveness Skill.
AB - Background: Forgiveness, as an intentional denial of your right of anger and
aversion from a harmful deed, is related to many psychological processes of human
which results in more psychological safety for people. The present study aimed to
predict the psychological safety of nurses through different dimensions of
forgiveness skill. Materials and Methods: This correlational study was conducted
on 170 nurses working in Kerman hospitals during 2016-2017 who were selected
based on convenience random sampling. Edmondson psychological safety and Thompson
Heartland forgiveness scale were used for data collection. Data were analyzed
through Pearson correlation coefficient and multiple regression model. Results:
TThe results indicated that psychological safety has a significant relationship
with self-forgiveness (p = 0.0001) and other-forgiveness (p = 0.04). Further,
only self-forgiveness could significantly predict 0.07 of psychological safety
variance (p = 0.003). Conclusions: Self-forgiveness skill can improve the nurses'
psychological safety and reduce the harms caused by job pressures by reinforcing
positive psychological factors. It is recommended to teach forgiveness skill
through holding in-service classes to staff and study the relationship between
psychological safety with other social life skills among nurses.
PMID- 29344046
TI - Relationship between Spiritual Intelligence with Happiness and Fear of Childbirth
in Iranian Pregnant Women.
AB - Background: Spiritual intelligence is a person's ability to feel a connection to
a higher power and a sacred entity. With regard to its relation with happiness,
it can have an important effect on the mental health of pregnant women.
Therefore, this study aimed to investigate the relationship between spiritual
intelligence and happiness and fear of childbirth in pregnant women. Materials
and Methods: This cross-sectional study was conducted on 245 low-risk pregnant
women from June till September 2015. Using random cluster sampling method, the
subjects were selected among the women who referred to health care centers in
Shahroud (Northeast of Iran). After obtaining informed consent, the researchers
evaluated the spiritual intelligence, happiness, and fear of childbirth. Data
were analyzed using STATA12 and Chi-square test, t-test, analysis of variance,
and Strucrural Equation Model. Results: In this study, the spiritual intelligence
mean (SD) score was 64.43(16.51). Comparison between mothers with and without
fear of childbirth showed there was a significant difference between the
spiritual intelligence score and happiness mean scores in these two groups. There
is a negative correlation between spiritual intelligence and happiness with fear
of childbirth (-0.73 and -0.69, respectively). Conclusions: Increased level of
spiritual intelligence in pregnant women can lead to an increase in their
happiness and reduce their fear of childbirth. The fear of childbirth can be
prevented via trainings to pregnant women about the components of spiritual
intelligence; moreover, training the techniques to achieve more happiness can
help mothers to reduce their fear of childbirth and hence promote natural
childbirth.
PMID- 29344047
TI - A Comparative Study of Shift Work Effects and Injuries among Nurses Working in
Rotating Night and Day Shifts in a Tertiary Care Hospital of North India.
AB - Background: Shift work can have an impact on the physical and psychological well
being of the healthcare worker, affecting patients as well as their own safety at
the workplace. This study was conducted to compare the health outcomes and
injuries, along with associated risk factors between the nurses working in
rotating night shift (RNS) as compared to day shift (DS) only. Materials and
Methods: It was a cross-sectional study conducted from June to November 2016 in a
tertiary care hospital of Delhi. It involved 275 nurses working in RNS and 275
nurses from DS of various departments, selected through simple random sampling.
Standard Shift Work Index Questionnaire (SSI) was used as the study instrument,
with selected variables (according to objectives of the study). Data were
analyzed using descriptive statistics, Chi-square, t-test, and multivariate
regression. Results: Female nurses had more sleep disturbance, fatigue, and poor
psychological health. Working on a contractual basis, RNS, and living outside the
hospital campus were associated with higher odds of having needle stick injury
(NSI). The nurses working in RNSs were found to have significantly lower mean
scores in job satisfaction (p = 0.04), sleep (p < 0.001), and psychological well
being (p = 0.047) as compared to DS workers. Conclusions: Health outcomes among
nurses working in RNSs call for the interventions, focused on various factors
which can be modified to provide supportive and safer working environment.
PMID- 29344048
TI - The Impact of Normal Saline on the Incidence of Exposure Keratopathy in Patients
Hospitalized in Intensive Care Units.
AB - Background: Patients in the intensive care unit (ICU) have impaired ocular
protective mechanisms that lead to an increased risk of ocular surface diseases
including exposure keratopathy (EK). This study was designed to evaluate the
effect of normal saline (NS) on the incidence and severity of EK in critically
ill patients. Materials and Methods: This single-blind randomized controlled
trial was conducted on 50 patients admitted to ICUs. The participants were
selected through purposive sampling. One eye of each patient, randomly was
allocated to intervention group (standard care with NS) and the other eye to
control group (standard care). In each patient, one eye (control group) randomly
received standard care and the other eye (intervention group) received NS every 6
h in addition to standard care. The presence and severity of keratopathy was
assessed daily until day 7 of hospitalization using fluorescein and an
ophthalmoscope with cobalt blue filter. Chi-square test was used for statistical
analysis in SPSS software. Results: Before the study ( first day) there were no
statistically significant differences in the incidence and severity of EK between
groups. Although, the incidence and severity of EK after the study (7th day) was
higher in the intervention group compared to the control group, their differences
were not statistically significant. Although, the incidence and severity of EK,
from the 1st day until the 7th, increased within both groups, this increase was
statistically significant only in the intervention (NS) group. Conclusions: The
use of NS as eye care in patients hospitalized in ICUs can increase the incidence
and severity of EK and is not recommended.
PMID- 29344049
TI - A Structural Equation Model of Self-care Activities in Diabetic Elderly Patients.
AB - Background: Self-care is a valuable strategy to improve health and reduce events
of hospitalization and the duration of hospital stay in elderly diabetic
patients. This study aimed to examine the model of self-care behaviors in elderly
diabetic patients. Materials and Methods: A survey was conducted among 209
diabetic elderly patients who were admitted in three hospitals affiliated with
the Isfahan University of Medical Sciences, Iran. Convenience sampling method was
used to recruit the participants. Depression, anxiety, stress, and perceived
social support were considered as predicting exogenous variables and elderly
patients' self-care activities were treated as endogenous variables. The data
were collected by a four-part questionnaire consisting of demographic and health
related characteristics; 21-item depression anxiety stress scale,
multidimensional scale of perceived social support, and Diabetes Self-care
Activities scale. Structural equation modelling by Statistical Package for the
Social Sciences (SPSS) version 16 and Analysis of Moment Structures-7 (AMOS)
software was applied for data analysis. Results: Mean (standard deviation) of
depression, anxiety, stress, perceived social support, and self-care activities
of participants were 14.29 (4.3), 13.62 (3.74), 16.83 (4.23), 57.33 (14.19), and
44.56 (13.77), respectively. The results showed that the overall model fitted the
data (chi2/df = 3.8, goodness-of-fit index (GFI) = 0.52, incremental fit index
(IFI) = 0.48, and root mean square error of approximation (RMSEA) = 0.14). Three
out of four variables (i.e., perceived social support, anxiety, and depression)
significantly predicted adherence to self-care behaviors among diabetic elderly
patients (p < 0.05). Conclusions: The perceived social support, anxiety, and
depression were identified as key constructs which need to be taken into account
and well managed by health care professionals to enhance adherence to self-care
activities in diabetic elderly patients.
PMID- 29344050
TI - The Lived Experiences of Becoming First-line Nurse Managers: A Phenomenological
Study.
AB - Background: Designated roles of first-line nurse managers (FLNMs) are very
complex, this study aimed to develop a deeper understanding of their meaningful
lived experiences. Materials and Methods: This study employed a phenomenological
study using semi-structured interviews with FLNMs (n = 7) at the General Hospital
of Belitung, Indonesia. The data analysis was thematic. Results: Four major
themes were identified from the analysis of textual data: Feeling extraordinary,
the inability to do, desire to leave the unit, and influenced by work motivation.
The findings of this study revealed the positive and negative experiences of
becoming FLNMs. The positive experiences were related to the feeling challenged
and extraordinary to deal with many roles in management and leadership. The
negative experiences included personal conflict related to the desire to leave
the unit, and feeling unable to manage. However, the works of FLNMs were
influenced by internal and external motivation. Conclusions: This study better
informs nurse executives to develop competence and performance of FLNMs, and keep
their motivation by revising performance appraisal system.
PMID- 29344051
TI - Experiences of Fathers with Inpatient Premature Neonates: Phenomenological
Interpretative Analysis.
AB - Background: Birth and hospitalization of premature neonates create enormous
challenges for the family with serious impacts on parents' mental and emotional
health. The present study was designed to explore the experiences of fathers with
premature neonates hospitalized in a neonatal intensive care unit (NICU).
Materials and Methods: In this interpretative phenomenological study, data were
collected using in-depth interviews guided with a semi-structured questionnaire
and analyzed by interpretative phenomenological analysis. Totally seven
interviews were conducted with six participants. Results: The mean age of the
fathers was 32 (23-42) years, and all of the fathers lived with their wives.
Experiences of the fathers were categorized into 13 subordinate and three
superordinate themes: "abandonment and helplessness" (lack of financial support,
lack of informational support, and indignation and distrust toward the hospital
staffs); "anxiety and confusion" (family disruption, shock due to the premature
birth of the neonate, uncertainty, the loss of wishes, feeling of guilt and
blame, and occupational disruption); and "development and self-actualization"
(emotional development, spiritual development, independence and self-efficacy,
and responsibility). Conclusions: The present study showed that the fathers with
premature neonates hospitalized in NICU encounter both positive (development and
self-actualization) and negative experiences (lack of financial and informational
supports, distrusting toward the hospital staffs, family disruption, and
occupational disruption). Planning to manage adverse experiences can help fathers
to cope with this situation.
PMID- 29344053
TI - An overview of exposure to ethanol-containing substances and ethanol intoxication
in children based on three illustrated cases.
AB - Alcohol addiction and intoxication are major health problems worldwide. Acute
alcohol intoxication is well reported in adults and adolescents but less
frequently reported in children of younger ages. We report three anonymized cases
of pediatric ethanol exposure and illustrate the different mechanisms of
intoxication. In all cases, a focused history is the key to prompt diagnosis and
timely management. Physicians should be aware of this potential poison in
children presented with acute confusional or encephalopathic state. In contrast,
neonates with ethanol intoxication may present with nonspecific gastrointestinal
symptomatology. Urgent exclusion of sepsis, electrolyte imbalance, drug
intoxication, and surgical abdominal condition is critical. Using these
illustrated cases, we performed a narrative literature review on issues of
exposure to ethanol-containing substances and ethanol intoxication in children.
In conclusion, a high level of suspicion and interrogation on ethanol or
substance use are essential particularly in the lactating mother for an accurate
and timely diagnosis of ethanol intoxication to be made.
PMID- 29344052
TI - Manidipine: an antihypertensive drug with positive effects on metabolic
parameters and adrenergic tone in patients with diabetes.
AB - Antihypertensive treatment of patients with diabetes should include those drugs
with a positive effect on metabolic parameters. Most patients with diabetes
require at least two antihypertensive agents. Combining a dihydropyridine calcium
channel blocker with a renin-angiotensin-aldosterone system inhibitor is a
rational approach. However, not all dihydropyridines are equal with respect to
their effects on metabolic parameters. Thus, manidipine exerts a positive effect
on insulin resistance. However, this effect has not been observed with
amlodipine. On the other hand, the excessive activation of sympathetic nervous
system has been related with an increase of insulin resistance, pulse pressure,
and ankle edema rates. Compared with amlodipine, manidipine activates sympathetic
nervous system to a lesser extent. As a result, treatment with manidipine
represents a good option in hypertensive patients with diabetes.
PMID- 29344054
TI - The carnitine status does not affect the contractile and metabolic phenotype of
skeletal muscle in pigs.
AB - Background: Recently, supplementation of L-carnitine to obese rats was found to
improve the carnitine status and to counteract an obesity-induced muscle fiber
transition from type I to type II. However, it has not been resolved if the
change of muscle fiber distribution induced in obese rats and the restoration of
the "normal" muscle fiber distribution, which is found in lean rats, in obese
rats by supplemental L-carnitine is causally linked with the carnitine status. In
the present study we hypothesized that fiber type distribution in skeletal muscle
is dependent on carnitine status. Methods: To test this, an experiment with 48
piglets which were randomly allocated to four groups (n = 12) was performed. All
piglets were given orally either 60 mg sodium bicarbonate/kg body weight (group
CON), 20 mg L-carnitine and 60 mg sodium bicarbonate/kg body weight (group CARN),
30 mg pivalate (dissolved in sodium bicarbonate)/kg body weight (group PIV) or 20
mg L-carnitine and 30 mg pivalate/kg body weight (group CARN + PIV) each day for
a period of 4 weeks. Results: Concentrations of total carnitine in plasma, liver
and longissimus dorsi and biceps femoris muscles were 2.0-2.7 fold higher in
group CARN than in group CON, whereas these concentrations were 1.9-2.5-fold
lower in group PIV than in group CON. The concentrations of total carnitine in
these tissues did not statistically differ between group CARN + PIV and group
CON. Fiber type distribution of longissimus dorsi and biceps femoris muscles,
mRNA and protein levels of molecular regulators of fiber distribution in
longissimus dorsi and biceps femoris muscles and mRNA levels of genes reflecting
the metabolic phenotype of longissimus dorsi and biceps femoris muscles did not
differ between groups. Conclusion: Changes in the systemic carnitine status and
the muscle carnitine concentration induced by either supplementing L-carnitine or
administering pivalate have no impact on the contractile and metabolic phenotype
of skeletal muscles in pigs.
PMID- 29344055
TI - Non-organic Vision Loss in the Afghanistan and Iraq Conflicts.
AB - Non-organic visual loss (NOVL), defined as a decrease in visual acuity or field
without an identifiable organic cause, can be challenging to diagnose, especially
in patients whose NOVL is superimposed on some component of true organic
pathology. Exposure to combat puts soldiers at risk of emotional distress and
physical trauma, which can contribute to the development of NOVL with conversion
disorder or malingering. This case series describes six patients with NOVL who
sustained ocular or non-ocular injuries while serving in combat operations in
Iraq and Afghanistan, and highlights diagnostic pearls and components of inter
disciplinary management in the unique military context.
PMID- 29344056
TI - Effects of Contrast Sensitivity on Colour Vision Testing.
AB - This study analyses how contrast sensitivity loss affects colour vision (CV)
testing. Eleven participants were scored while cycling through randomly arranged
pictures of CV tests with varying levels of contrast changes applied. Hardy-Rand
Rittler (HRR) scores declined significantly at each successive decrease in
contrast level after the highest setting (p < 0.004). HRR scores were also lower
than those for Ishihara and Farnsworth D-15 tests at two contrast settings (p <
0.01). Contrast changes had the greatest impact on HRR scores, indicating that
this test may not be an accurate reflection of CV in patients with contrast
sensitivity loss.
PMID- 29344057
TI - Causes and Prognosis of Unilateral and Bilateral Optic Disc Swelling.
AB - The authors reviewed 93 consecutive cases with optic disc swelling (ODS) to
compare clinical manifestations and prognosis among the causes. Among unilateral
ODS patients >=50 years old and without pain, anterior ischaemic optic neuropathy
accounted for 87.5%. Furthermore, papilloedema (PE) presented unilateral ODS with
an atrophic or hypoplastic disc in the opposite eye. Despite no differences for
age and initial visual acuity between PE and pseudopapilloedema, the two main
causes of bilateral ODS, some PE patients showed poor visual prognosis.
Understanding differences in frequencies and clinical features of ODS related to
cause and age group can help to accurately determine cause and predict outcome.
PMID- 29344058
TI - An Estimation of the Risk of Pseudotumor Cerebri among Users of the
Levonorgestrel Intrauterine Device.
AB - Because of a previous association of pseudotumor cerebri (PTC) with
levonorgestrel, we wished to evaluate the use of levonorgestrel-eluting
intrauterine devices ("levonorgestrel intrauterine systems", LNG-IUS) in our
University of Utah and Rigshospitalet PTC patients. In our retrospective series,
PTC prevalence was approximately 0.18% and 0.15% in the LNG-IUS population versus
0.02% and 0.04% in the non-LNG-IUS population (Utah and Rigshospitalet,
respectively), with no significant differences in PTC signs and symptoms among
the two groups. Our investigation suggests that women with an LNG-IUS may have
increased risk of developing PTC but does not suggest an LNG-IUS can cause PTC.
PMID- 29344059
TI - Retinitis Pigmentosa Sine Pigmento Mimicking a Chiasm Disease.
AB - A 75-year-old woman presented to her ophthalmologist complaining of visual loss
for several years. The ophthalmic examination was remarkable for a bitemporal
visual field defect. Magnetic resonance imaging (MRI) scan of the brain was
normal without evidence of chiasm compression. Neuro-ophthalmic examination was
consistent with a retinal rather than a chiasmal disease. Retinal multimodal
imaging helped in the correct diagnosis of retinitis pigmentosa, later confirmed
by genetic testing.
PMID- 29344060
TI - Neuro-Ophthalmic Presentation of Neuro-Sweet Disease.
AB - Acute febrile neutrophilic dermatosis (Sweet syndrome) is a systemic inflammatory
condition usually associated with autoimmune or neoplastic processes and
characterised by inflammatory dermatologic lesions such as erythematous plaques
and papules associated with fever and leukocytosis. Neurological and
ophthalmological involvement is rare. The authors describe an unusual case of
Sweet syndrome associated with microscopic polyangiitis presenting with
papilloedema, anterior uveitis, and skin rash. Years later, he developed acute
posterior multifocal placoid pigment epitheliopathy. Treatment with
immunosuppressive medications led to a relapsing remitting course with maximum
benefit from use of steroids. The authors describe the difficulties in diagnosis
and treatment of this rare case.
PMID- 29344061
TI - Subacute Acrylamide Intoxication with Severe Visual Disturbance: A Case Report.
AB - A 35-year-old man was admitted due to somnolence and progressive sensory-motor
polyneuropathy, followed by severe visual impairment in both eyes after direct
skin exposure to an acrylamide monomer solution. The results of an
ophthalmological examination including central critical flicker fusion frequency
and the decreased amplitude of action potentials observed in the visual evoked
potential studies suggested that acrylamide intoxication resulted in neuronal
degeneration in the optic pathways. Additional attention should be directed to
the potential effect of acrylamide on the human visual system.
PMID- 29344062
TI - Cystic Optic Chiasm Lesion: Atypical Magnetic Resonance Imaging Findings.
AB - Intrinsic cystic lesions in the optic chiasm are an uncommon cause of bitemporal
hemianopia compared with compressive lesions extrinsic to the chiasm. A 40-year
old man presented with difficulty driving. Clinical assessment revealed a
bitemporal hemianopia. Magnetic resonance imaging showed an unusual cystic
appearance of the chiasm. The appearance was felt to be most likely secondary to
previous infective or inflammatory disease, but biopsy was not undertaken given
the very significant risk of further visual loss.
PMID- 29344063
TI - Axonal Injury in the Lateral Geniculate Body: Radiological Diagnosis.
AB - Damage to the lateral geniculate body by diffuse axonal injury in brain trauma is
uncommon. The authors present the clinical case and in vivo fibre tractography
using diffusion tensor magnetic resonance imaging of this lesion in a patient
presenting with homonymous sectoranopia after a traumatic head injury.
PMID- 29344064
TI - Occult Acute Macular Neuroretinopathy.
AB - A 19-year-old Caucasian woman developed an upper respiratory infection, took a
cold formulation containing 5 mg of phenylephrine, and developed a very rare and
unusual form of acute macular neuroretinopathy (AMN) that could not be detected
on fundoscopic examination, visual fields, nor electrophysiological testing.
Spectral-domain optical coherence tomography (SD-OCT) revealed a lesion limited
to the fovea. This case illustrates the value of SD-OCT, in light of otherwise
normal testing, in a variant of AMN the authors call "occult AMN".
PMID- 29344065
TI - Optociliary Shunt Vessels: Role in Diagnosis and Treatment of Atypical
Pseudotumor Cerebri.
AB - A 46-year-old man presented with severe visual loss and optic atrophy associated
with optociliary shunt vessels. The diagnostic work-up revealed intracranial
hypertension and cerebral venous sinus stenosis, with no evidence of previous
thrombosis. In view of the severe visual dysfunction, both eyes were submitted to
optic nerve sheath fenestration. After surgery, a regression of collateral
vessels was observed in both eyes.
PMID- 29344066
TI - Diagnostic Challenge: Sequential Unilateral Cranial Neuropathies Due to
Perineural Spread of Carcinoma.
AB - An 86-year old man developed sequential dysfunction of trigeminal (V1), facial,
abducens, trigeminal (v2), oculomotor, and hypoglossal cranial nerves on the
right over 20 months. Magnetic resonance imaging (MRI) showed a lesion in the
right cavernous sinus. Although there was clinical suspicion that this was
related to perineural spread of an extracranial tumour, a primary lesion was not
discovered. Stereotactic biopsies of the intracranial lesion were non-diagnostic,
and the patient succumbed to his tumour following a period of rapid growth.
Postmortem examination showed the intracranial lesion to be a carcinoma with
squamous features. This case highlights the challenges of diagnosis of
intracranial perineural spread and the potential for transformation from indolent
to aggressive tumour behaviour.
PMID- 29344067
TI - Corrigendum.
AB - [This corrects the article DOI: 10.1080/01658107.2016.1263343.].
PMID- 29344069
TI - Pituitary Ring Sign Plus Sphenoid Sinus Mucosal Thickening: Neuroimaging Signs of
Pituitary Apoplexy.
AB - Two magnetic resonance imaging (MRI) signs of pituitary apoplexy are the
"pituitary ring sign" and "sphenoid sinus mucosal thickening". The occurrence of
both these MRI signs together in patients with ischaemic pituitary apoplexy was
investigated. A literature review searching the terms "pituitary ring sign" and
"sphenoid sinus mucosal thickening" in the context of pituitary apoplexy from
1990 until present was performed. To be included in the study, each case had to
have ischaemic pituitary apoplexy defined as acute expansion of a pituitary
adenoma or, less commonly, in a non-adenomatous gland, from infarction without
haemorrhage or very little haemorrhage and a T1-weighted MRI of the brain with
contrast that displayed both "sphenoid sinus mucosal thickening" and a "pituitary
ring sign" either on an actual study (the author's cases) or in a figure in an
article from the literature that could be reviewed and clearly illustrate these
two signs. Twelve cases of ischaemic pituitary apoplexy were found, all with MRI
images that showed both of these signs. Ten cases from the literature (3 of which
were published by this author) plus an additional 2 recently evaluated in our
hospital, totalled the 12 cases. Thus, 5 of the total 12 cases were evaluated by
this author. Of these 12 patients, both headache and visual loss were present in
5 patients, headache alone was indicated in 5 patients (10 of the 12 presented
with headache), and no initial symptoms identified in 2 patients (incidentally
found non-functioning pituitary adenomas on MRI). These findings indicate that
each sign ("pituitary ring sign" and "sphenoid sinus mucosal thickening") may
exist alone with or without pituitary apoplexy, yet both signs together in the
appropriate clinical context is a strong predictor of pituitary apoplexy.
PMID- 29344068
TI - Clinical versus Evidence-based Rehabilitation Options for Post-stroke Visual
Impairment.
AB - The aim of this study was to identify which treatments for post-stroke visual
impairment have a supportive evidence base, and which are being used in practice
without supportive evidence. A systematic review of the literature reporting on
the available treatment options was compared against the visual treatments used
in the Vision In Stroke (VIS) study. Treatments were identified for visual field,
visual neglect, visual perception and ocular motility disorders. Visual scanning
therapies for hemianopia and neglect have an established evidence base. However,
a number, such as typoscopes and advice options, have limited detail of their
effectiveness and require further research.
PMID- 29344070
TI - Diffuse Colour Discrimination as Marker of Afferent Visual System Dysfunction in
Amyotrophic Lateral Sclerosis.
AB - Abnormalities of the inner and intermediate retinal structures in patients with
amyotrophic lateral sclerosis (ALS) have been described using optical coherence
tomography and histopathology. Colour vision is a potential marker of these
structural changes. The purpose of this study is to test the hypothesis that
colour vision impairment is associated with ALS. Monocular (right eye) colour
vision was assessed in subjects with definite or probable ALS (n = 25, aged 50-80
years) and control (n = 21, aged 46-89 years) subjects with corrected near visual
acuity of at least 20/40 using the L'Anthony D15 color test (desaturated), scored
by c-index, a measure of diffuse colour discrimination. Of ALS subjects, 16/25
(64%) had impaired colour vision (c-index >1.8). Comparing with our normal
subjects and accounting for age, 72% (n = 18) of ALS subjects had colour vision
below the 50th percentile, 52% (n = 13) had colour vision below the 25th
percentile, 24% (n = 6) had colour vision below the 10th percentile, and 8% (n =
2) had colour vision below the 2nd percentile. In multivariate models of ln(c
index) and age, the intercept was higher and the slope was flatter in ALS
subjects, suggesting that colour vision deficits are more prominent in younger
ALS patients. Diffuse colour discrimination deficits are detected in ALS subjects
at younger ages than in control subjects. Further study is needed to confirm
these findings and to determine if the ALS colour discrimination abnormalities
correlate with structural markers of retinal involvement and ALS disease
severity.
PMID- 29344071
TI - Acetazolamide: A New Treatment for Visual Vertigo.
AB - Visual vertigo is a disorder characterised by symptoms of dizziness, vertigo,
unsteadiness, disorientation, and general discomfort induced by visual triggers.
It is currently treated with vestibular rehabilitation therapy, with no effective
pharmacotherapy available for treatment-resistant cases. The objective of this
study was to evaluate the efficacy of oral acetazolamide in improving symptoms of
visual vertigo. A comparative case series of adult patients clinically diagnosed
with visual vertigo was conducted from January 1992 to May 2015. Patients without
a full neurologic or otorhinolaryngologic work-up, negative magnetic resonance
imaging (MRI), and an organic cause for their symptoms were excluded. The
identified patients were then contacted by phone to complete a voluntary symptom
survey. Main outcome was the subjective reported percentage in symptom
improvement. Secondary outcomes were subjective improvement by symptom triggers.
The participants were retrospectively divided into three groups based on their
treatment with acetazolamide: currently on acetazolamide, terminated
acetazolamide, or never initiated acetazolamide. Fifty-seven patients met the
inclusion criteria and were willing to complete the phone survey (19 currently on
acetazolamide, 27 terminated acetazolamide, and 11 never initiated therapy).
Overall symptomatic improvement was reported by 18 (94.7%) patients currently on
acetazolamide, 18 (66.7 %) who terminated acetazolamide, and 5 (45.5%) who never
initiated therapy, varying significantly by group (p = 0.0061). Greatest
improvement was reported in symptoms triggered by being a passenger in a car.
These results show that acetazolamide has a positive association with improvement
of symptoms of visual vertigo.
PMID- 29344072
TI - Bilateral Compressive Optic Neuropathy from Renal Osteodystrophy Caused by
Branchio-oto-renal Syndrome Stabilised After Parathyroidectomy.
AB - Renal osteodystrophy can cause calvarial hypertrophy and narrowing of the neural
canals and foramina. Compressive optic neuropathy is extremely rare in renal
osteodystrophy and was reported once only. The authors report bilateral,
simultaneous compressive optic neuropathy secondary to renal osteodystrophy with
features of uremic leontiasis ossea in chronic renal failure caused by branchio
oto-renal syndrome. Because of the extensive calvarial hypertrophy and the
surgical difficulties envisaged with optic canal decompression, conservative
approach was pursued. The patient's visual acuity and fields improved after
partial parathyroidectomy. Visual improvement may be explained by the arrest of
renal osteodystrophy and reduced optic nerve compression after parathyroidectomy.
PMID- 29344073
TI - Bilateral Non-arteritic Anterior Ischaemic Optic Neuropathy as the Presentation
of Systemic Amyloidosis.
AB - A 75-year-old hypertensive female with stable idiopathic intermediate uveitis
presented with bilateral sequential optic neuropathy with optic disc swelling.
The optic neuropathy in the first affected eye (right) was thought to be due to
non-arteritic anterior ischaemic optic neuropathy (NAION). Asymptomatic left
optic disc swelling was found at routine review 2 months later, and a diagnosis
of giant cell arteritis (GCA) was sought. Temporal artery duplex ultrasound
showed the "halo sign," but a subsequent temporal artery biopsy showed light
chain (AL) amyloidosis with no signs of giant cell arteritis. In this case,
bilateral sequential ischaemic optic neuropathy mimicking non-arteritic anterior
ischaemic optic neuropathy was the presenting sign of systemic amyloidosis
involving the temporal arteries.
PMID- 29344074
TI - Proceedings of the 38th Annual Upper Midwest Neuro-Ophthalmology Group Meeting,
July 28, 2017, Chicago, Illinois, USA.
PMID- 29344075
TI - Reply to: "Bilateral Non-arteritic Anterior Ischaemic Optic Neuropathy as the
Presentation of Systemic Amyloidosis".
PMID- 29344076
TI - Response to Dr. Pellegrini Regarding Comments on "Bilateral Non-arteritic
Anterior Ischaemic Optic Neuropathy as the Presentation of Systemic Amyloidosis".
PMID- 29344078
TI - Application of the ICF based Norwegian function assessment scale to employees in
Germany.
AB - Background: At the interface of the occupational setting and rehabilitation,
normative values for functional ability are desirable and worthwhile. The
Norwegian Function Assessment Scale (NFAS) is a 39 item self-report instrument
based on the International Classification of Functioning, Disability and Health
(ICF). As the questionnaire was not used in a working population, we aimed to
obtain functional levels of employees in Germany as measured through the NFAS.
Methods: The NFAS was included in the Study on Mental Health at Work (S-MGA)
2011/12, a representative German survey of employees aged 31 to 60 years. For
descriptive analyses, 95% confidence intervals were applied through bootstrap
estimation to the skewed data of the NFAS (range from 1 = 'no difficulty' to 5 =
'could not do it'). The data were analysed by age decades, professional
qualification, and by disabilities, congenital diseases and accidents, stratified
by sex. Linear regression analyses were conducted to estimate adjusted effects of
age, professional qualification, and health limitations. Results: The NFAS total
score was 1.17 (95% CI = 1.15-1.17). Thirty-five percent of the employees' (1378
out of 3937 participants) reported the best possible functional ability (NFAS
total score of 1.00). Managing and walking/standing were the NFAS' most affected
domains with a score of 1.26 (95% CI = 1.23-1.27), respectively. The regression
analysis confirmed more functional difficulties for elder employees, females,
employees with low professional qualification, and for employees suffering from
disability and accidents. Conclusions: The study presents normative values of
functional ability for the workforce. The results are useful for score
interpretation in rehabilitation and return-to-work processes.
PMID- 29344079
TI - Factors associated with breastfeeding intent among mothers of newborn babies in
Da Nang, Viet Nam.
AB - Background: Breastfeeding is recognized as the single most cost-effective
intervention to reduce child morbidity and mortality. However, few studies have
explored perceived barriers to breastfeeding and factors associated with
breastfeeding intent among mothers of newborn babies in Viet Nam. We conducted a
study to assess breastfeeding initiation rates, intent to breastfeed exclusively
for 6 months or more and perceived barriers to breastfeed among mothers of
newborn babies in Da Nang, Viet Nam. Methods: We conducted a cross-sectional
questionnaire survey of mothers in the postnatal wards of Da Nang Hospital for
Women and Children in central Viet Nam from 10 February 2017 to 24 February 2017,
following implementation of the World Health Organization (WHO) Essential Newborn
Care (ENC) package. Results: Of 286 mothers surveyed, 259 (90.6%) initiated
breastfeeding; 203/258 (78.7%) within 1 hour (h) of birth. Most (207, 72.4%)
mothers indicated intent to breastfeed exclusively for 6 months or more, but this
was lower among mothers of preterm babies (82.2% versus 20.0%, p < 0.001) and
those without post-secondary school education (74.8% versus 55.6%, p = 0.02).
Amongst mothers struggling to establish breastfeeding, 18/27 (66.7%) had a
Cesarean section. Planned non-exclusive breastfeeding was mostly (39, 60.9%)
motivated by mothers' concern that their milk supply would be insufficient for
their baby's growth requirements. Most mothers had good knowledge about the
benefits of breastfeeding and indicated strong decision autonomy. Conclusions: We
documented high rates of early breastfeeding establishment and intent to
breastfeed exclusively for 6 months or more. This probably reflects high levels
of maternal education and successful implementation of the WHO ENC package.
Mothers of premature babies may benefit from additional support.
PMID- 29344081
TI - HPV infection and P16 expression in oral and oropharyngeal cancer in Kazakhstan.
AB - Background: Human papillomavirus (HPV) is an important etiologic factor in
different cancers of anogenital region and also in a fraction of head and neck
cancers (HNC) particularly oropharyngeal tumors. The HPV16 genotype associated
with the majority of HPV-related head and neck carcinomas. Th incidence of
oropharyngeal cancer is increasing in many countries, and the rate of HPV
positive tumors is about 70% in Europe and North America. Little known about the
prevalence of HPV in HNC in Central Asia. Methods: It's a prospective analysis of
patients with verified oral or oropharyngeal cancer. Sociodemographic and
clinical data obtained on admission to treatment. The diagnosis of HPV positivity
assessed by both the P16 expression on immunohistochemistry(IHC) and polymerase
chain reaction (PCR)with HPV DNA detection and HR HPV type determination.
Results: Seventy six patients with oral and oropharyngeal cancer tested for HPV.
Forteen cases were positive for HPV by PCR and 15 cases by P16 IHC. Of the 35
oropharyngeal tumors, nine were HPV DNA and p16 IHC positive, giving the rate of
25.7%. Of the 41 oral tumors, five were HPV DNA and six p16 IHC positive, giving
the rate of 12.2%. Conclusion: It is the first study mapping prevalence of HPV
positivity in oral and oropharyngeal cancer in the Central Asian region. The rate
of HPV positivity was higher in oropharyngeal than in oral cancer, the nonsmokers
were significantly more frequent in the HPV positive group and HPV 16 was the
most frequent type. However, the HPV positivity rates are lower than referred in
the western world.
PMID- 29344080
TI - Effects of Huang Bai (Phellodendri Cortex) on bone growth and pubertal
development in adolescent female rats.
AB - Background: To evaluate the effects of Huang Bai (Phellodendron amurense) on
growth and maturation in adolescent female rats. Methods: Female Sprague-Dawley
rats (28 days old; n = 72) were divided into six daily treatment groups: control
(distilled water), Huang Bai (100 and 300 mg/kg), recombinant human GH (rhGH; 20
MUg/kg), estradiol (1 MUg/kg), and triptorelin (100 MUg). Body weight, food
intake, and vaginal opening were measured daily from postnatal day (PND) 28 to
PND 43. Tetracycline (20 mg/kg) was injected on PND 41. After sacrifice on PND
43, the ovaries and uterus were weighed, and the tibias were fixed in 4%
paraformaldehyde. Decalcified and dehydrated tibias were sectioned at a thickness
of 40 MUm, and sectioned tissues were examined with a fluorescence microscope.
Insulin-like growth factor (IGF)-1 and bone morphogenetic protein (BMP)-2 were
detected using immunohistochemistry. Results: Relative to controls, body weight
was higher in the triptorelin group. Bone growth rate increased in the Huang Bai
100 mg/kg (354.00 +/- 31.1 MUm/day), rhGH (367.10 +/- 27.11 MUm/day), and
triptorelin (374.50 +/- 25.37 MUm/day) groups. Expression of IGF-1 and BMP-2 in
the hypertrophic zone was higher in all experimental groups. Vaginal opening
occurred earlier in the estradiol group (PND 33.58 +/- 1.62) than in controls and
later in the triptorelin group (PND > 43). Ovarian and uterine weights were lower
in the oestradiol and triptorelin groups. However, Huang Bai had nonsignificant
effects on vaginal opening and the weights of ovaries and the uterus.
Conclusions: Huang Bai stimulated bone growth by upregulating IGF-1 and BMP-2 in
the growth plate. However, it had no effect on pubertal development.
PMID- 29344082
TI - Implementing guidelines on physical health in the acute mental health setting: a
quality improvement approach.
AB - Background: In the UK, life expectancy for people living with a serious mental
illness, such as schizophrenia and bipolar disorder, is reduced by 15-20 years
compared with the general population. In recent years, evidence based
guidelines/policies designed to improve their physical health have been
published, yet a gap remains between recommendations and practice. This case
study describes how guidelines to support physical health were implemented using
a quality improvement approach. Case presentation: A quasi-experimental study
explored systems and processes for assessing the physical health of patients
admitted to an acute mental health unit. The multi-disciplinary team of
healthcare professionals, service users and experts in quality improvement
methods developed solutions to improve the assessment of physical health, drawing
on existing guidelines/policies as well as professional and lived experience.
Three key interventions were developed: a comprehensive physical health
assessment; a patient-held physical health booklet; and education and training
for staff and patients. Interventions were co-designed by front-line healthcare
staff and service users with iterative development and implementation through
Plan-Do-Study-Act cycles. Real-time weekly data were reported on five measures
over a 15-month implementation period (318 patients) and compared to a 10-month
baseline period (247 patients) to gauge the success of the implementation of the
physical health assessment. Improvements were seen in the numbers of patients
receiving a physical health assessment: 81.3% (201/247) vs 96.9% (308/318),
recording of body mass index: 21.55% (53/247) vs 58.6% (204/318) and systolic
blood pressure: 22.35% (55/247) vs 75.9% (239/318) but a reduction in the
recording of smoking status: 80.1% (198/247) vs 70.9% (225/318). However, 31.7%
(118/318) patients had a cardiovascular risk-score documented in the
implementation phase, compared to none in the baseline. Conclusion: This study
demonstrates the use of a quality improvement approach to support teams to
implement guidelines on physical health in the acute mental health setting.
Reflections of the team have identified the need for resources, training, support
and leadership to support changes to the way care is delivered. Furthermore,
collaborations between service users and frontline clinical staff can co-design
interventions to support improvements and raise awareness of the physical health
needs of this population.
PMID- 29344083
TI - Psychosocial problems in traumatized refugee families: overview of risks and some
recommendations for support services.
AB - This article is an abridged version of a report by an advisory council to the
German government on the psychosocial problems facing refugee families from war
zones who have settled in Germany. It omits the detailed information contained in
the report about matters that are specific to the German health system and asylum
laws, and includes just those insights and strategies that may be applicable to
assisting refugees in other host countries as well. The focus is on understanding
the developmental risks faced by refugee children when they or family members are
suffering from trauma-related psychological disorders, and on identifying
measures that can be taken to address these risks. The following recommendations
are made: recognizing the high level of psychosocial problems present in these
families, providing family-friendly living accommodations, teaching positive
parenting skills, initiating culture-sensitive interventions, establishing
training programs to support those who work with refugees, expanding the
availability of trained interpreters, facilitating access to education and health
care, and identifying intervention requirements through screening and other
measures.
PMID- 29344084
TI - The Strengths and Difficulties Questionnaire (SDQ) in Africa: a scoping review of
its application and validation.
AB - Background: Child and adolescent mental health in Africa remains largely
neglected. Quick and cost-effective ways for early detection may aid early
intervention. The Strengths and Difficulties Questionnaire (SDQ) is globally used
to screen for mental health problems, but little is known about its use in
Africa. We set out to perform a scoping review to examine existing studies that
have used the SDQ in Africa. Methods: A comprehensive scoping review methodology
was used to identify all peer-reviewed studies ever published that have used the
SDQ in Africa. Data were extracted and analysed to assess the countries,
languages and SDQ versions used, the purpose of the SDQ studies, psychometric
properties of the SDQ, and to consider knowledge gaps for future in-country and
cross-country studies. Results: Fifty-four studies from 12 African countries were
identified, most from South Africa. Many different languages were used, but
authorized SDQs in those languages were not always available on the SDQinfo
website. Authors frequently commented on challenges in the translation and
backtranslation of mental health terminology in African languages. The SDQ was
typically used to investigate internalisation/externalization disorders in
different clinical populations, and was most frequently used in the evaluation of
children and adolescents affected by HIV/AIDS. Sixteen studies (29.6%)
administered the SDQ to participants outside the intended age range, only 4
(7.4%) used triangulation of all versions to generate assessments, and eight
studies (14.8%) used only subscales of the SDQ. Only one study conducted thorough
psychometric validation of the SDQ, including examination of internal consistency
and factor analysis. Where 'caseness' was defined in studies, UK cut-off scores
were used in all but one of the studies. Conclusions: The SDQ may be a very
useful tool in an African setting, but the scoping review suggested that, where
it was used in Africa researchers did not always follow instrument guidelines,
and highlighted that very little is known about the psychometric properties of
the SDQ in Africa. We recommend comprehensive evaluation of the psychometric
properties of the SDQ in various African languages, including internal
consistency, factor structure, need for local cut-off values and ensuring
cultural equivalence of the instrument.
PMID- 29344086
TI - Correlation of structure, function and protein dynamics in GH7 cellobiohydrolases
from Trichoderma atroviride, T. reesei and T. harzianum.
AB - Background: The ascomycete fungus Trichoderma reesei is the predominant source of
enzymes for industrial conversion of lignocellulose. Its glycoside hydrolase
family 7 cellobiohydrolase (GH7 CBH) TreCel7A constitutes nearly half of the
enzyme cocktail by weight and is the major workhorse in the cellulose hydrolysis
process. The orthologs from Trichoderma atroviride (TatCel7A) and Trichoderma
harzianum (ThaCel7A) show high sequence identity with TreCel7A, ~ 80%, and
represent naturally evolved combinations of cellulose-binding tunnel-enclosing
loop motifs, which have been suggested to influence intrinsic cellobiohydrolase
properties, such as endo-initiation, processivity, and off-rate. Results: The
TatCel7A, ThaCel7A, and TreCel7A enzymes were characterized for comparison of
function. The catalytic domain of TatCel7A was crystallized, and two structures
were determined: without ligand and with thio-cellotriose in the active site.
Initial hydrolysis of bacterial cellulose was faster with TatCel7A than either
ThaCel7A or TreCel7A. In synergistic saccharification of pretreated corn stover,
both TatCel7A and ThaCel7A were more efficient than TreCel7A, although TatCel7A
was more sensitive to thermal inactivation. Structural analyses and molecular
dynamics (MD) simulations were performed to elucidate important
structure/function correlations. Moreover, reverse conservation analysis (RCA) of
sequence diversity revealed divergent regions of interest located outside the
cellulose-binding tunnel of Trichoderma spp. GH7 CBHs. Conclusions: We
hypothesize that the combination of loop motifs is the main determinant for the
observed differences in Cel7A activity on cellulosic substrates. Fine-tuning of
the loop flexibility appears to be an important evolutionary target in
Trichoderma spp., a conclusion supported by the RCA data. Our results indicate
that, for industrial use, it would be beneficial to combine loop motifs from
TatCel7A with the thermostability features of TreCel7A. Furthermore, one region
implicated in thermal unfolding is suggested as a primary target for protein
engineering.
PMID- 29344087
TI - Determination of the native features of the exoglucanase Cel48S from Clostridium
thermocellum.
AB - Background: Clostridium thermocellum is considered one of the most efficient
natural cellulose degraders because of its cellulosomal system. As the major
exoglucanase of cellulosome in C. thermocellum, Cel48S plays key roles and
influences the activity and features of cellulosome to a great extent. Thus, it
is of great importance to reveal the enzymatic features of Cel48S. However,
Cel48S has not been well performed due to difficulties in purifying either
recombinant or native Cel48S proteins. Results: We observed that the soluble
fraction of the catalytic domain of Cel48S (Cel48S_CD) obtained by heterologous
expression in Escherichia coli and denaturation-refolding treatment contained a
large portion of incorrectly folded proteins with low activity. Using a
previously developed seamless genome-editing system for C. thermocellum, we
achieved direct purification of Cel48S_CD from the culture supernatant of C.
thermocellum DSM1313 by inserting a sequence encoding 12 successive histidine
residues and a TAA stop codon immediately behind the GH domain of Cel48S. Based
on the fully active protein, biochemical and structural analyses were performed
to reveal its innate characteristics. The native Cel48S_CD showed high activity
of 117.61 +/- 2.98 U/mg and apparent substrate preference for crystalline
cellulose under the assay conditions. The crystal structure of the native GH48
protein revealed substrate-coupled changes in the residue conformation,
indicating induced-fit effects between Cel48S_CD and substrates. Mass spectrum
and crystal structural analyses suggested no significant posttranslational
modification in the native Cel48S_CD protein. Conclusion: Our results confirmed
that the high activity and substrate specificity of Cel48S_CD from C.
thermocellum were consistent with its importance in the cellulosome. The
structure of the native Cel48S_CD protein revealed evidence of conformational
changes during substrate binding. In addition, our study provided a reliable
method for in situ purification of cellulosomal and other secretive proteins from
C. thermocellum.
PMID- 29344088
TI - Incidence and root causes of delays in emergency orthopaedic procedures: a single
centre experience of 36,017 consecutive cases over seven years.
AB - Background: Emergency surgery is unplanned by definition and patients are
scheduled for surgery with minimal preparation. Some patients who have sustained
emergency orthopaedic trauma or other conditions must be operated on immediately
or within a few hours, while others can wait until the hospital's resources
permit and/or the patients' health status has been optimised as needed. This may
affect the prioritisation procedures for both emergency and elective surgery and
might result in waiting lists, not only for planned procedures but also for
emergencies. Method: The main purpose of this retrospective, observational,
single-centre study was to evaluate and describe for the number and reasons of
delays, as well as waiting times in emergency orthopaedic surgery using data
derived from the hospital's records and registers. All the emergency patients
scheduled for emergency surgery whose procedures were rescheduled and delayed
between 1 January 2007 and 31 December 2013 were studied. Result: We found that
24% (8474) of the 36,017 patients scheduled for emergency surgeries were delayed
and rescheduled at least once, some several times. Eighty per cent of these
delays were due to organisational causes. Twenty-one per cent of all the delayed
patients had surgery within 24 h, whilst 41% waited for more than 24 h, up to 3
days. Conclusion: A large number of the clinic's emergency orthopaedic procedures
were rescheduled and delayed and the majority of the delays were related to
organisational reasons. The results can be interpreted in two ways; first,
organisational reasons are avoidable and the potential for improvement is great
and, secondly and most importantly, the delays might negatively affect patient
outcomes.
PMID- 29344085
TI - Synthesis, secretion, function, metabolism and application of natriuretic
peptides in heart failure.
AB - As a family of hormones with pleiotropic effects, natriuretic peptide (NP) system
includes atrial NP (ANP), B-type NP (BNP), C-type NP (CNP), dendroaspis NP and
urodilatin, with NP receptor-A (guanylate cyclase-A), NP receptor-B (guanylate
cyclase-B) and NP receptor-C (clearance receptor). These peptides are genetically
distinct, but structurally and functionally related for regulating circulatory
homeostasis in vertebrates. In humans, ANP and BNP are encoded by NP precursor A
(NPPA) and NPPB genes on chromosome 1, whereas CNP is encoded by NPPC on
chromosome 2. NPs are synthesized and secreted through certain mechanisms by
cardiomyocytes, fibroblasts, endotheliocytes, immune cells (neutrophils, T-cells
and macrophages) and immature cells (embryonic stem cells, muscle satellite cells
and cardiac precursor cells). They are mainly produced by cardiovascular, brain
and renal tissues in response to wall stretch and other causes. NPs provide
natriuresis, diuresis, vasodilation, antiproliferation, antihypertrophy,
antifibrosis and other cardiometabolic protection. NPs represent body's own
antihypertensive system, and provide compensatory protection to counterbalance
vasoconstrictor-mitogenic-sodium retaining hormones, released by renin
angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS). NPs
play central roles in regulation of heart failure (HF), and are inactivated
through not only NP receptor-C, but also neutral endopeptidase (NEP), dipeptidyl
peptidase-4 and insulin degrading enzyme. Both BNP and N-terminal proBNP are
useful biomarkers to not only make the diagnosis and assess the severity of HF,
but also guide the therapy and predict the prognosis in patients with HF. Current
NP-augmenting strategies include the synthesis of NPs or agonists to increase NP
bioactivity and inhibition of NEP to reduce NP breakdown. Nesiritide has been
established as an available therapy, and angiotensin receptor blocker NEP
inhibitor (ARNI, LCZ696) has obtained extremely encouraging results with
decreased morbidity and mortality. Novel pharmacological approaches based on NPs
may promote a therapeutic shift from suppressing the RAAS and SNS to re-balancing
neuroendocrine dysregulation in patients with HF. The current review discussed
the synthesis, secretion, function and metabolism of NPs, and their diagnostic,
therapeutic and prognostic values in HF.
PMID- 29344089
TI - Bone marrow failure may be caused by chromosome anomalies exerting effects on
RUNX1T1 gene.
AB - Background: The majority of the cases of bone marrow failure syndromes/aplastic
anaemias (BMFS/AA) are non-hereditary and considered idiopathic (80-85%). The
peripheral blood picture is variable, with anaemia, neutropenia and/or
thrombocytopenia, and the patients with idiopathic BMFS/AA may have a risk of
transformation into a myelodysplastic syndrome (MDS) and/or an acute myeloid
leukaemia (AML), as ascertained for all inherited BMFS. We already reported four
patients with different forms of BMFS/AA with chromosome anomalies as primary
etiologic event: the chromosome changes exerted an effect on specific genes,
namely RUNX1, MPL, and FLI1, leading to the disease. Results: We report two
further patients with non-hereditary BM failure, with diagnosis of severe
aplastic anaemia and pancytopenia caused by two different constitutional
structural anomalies involving chromosome 8, and possibly leading to the disorder
due to effects on the RUNX1T1 gene, which was hypo-expressed and hyper-expressed,
respectively, in the two patients. The chromosome change was unbalanced in one
patient, and balanced in the other one. Conclusions: We analyzed the sequence of
events in the pathogenesis of the disease in the two patients, including a number
of non-haematological signs present in the one with the unbalanced anomaly. We
demonstrated that in these two patients the primary event causing BMFS/AA was the
constitutional chromosome anomaly. If we take into account the cohort of 219
patients with a similar diagnosis in whom we made cytogenetic studies in the
years 2003-2017, we conclude that cytogenetic investigations were instrumental to
reach a diagnosis in 52 of them. We postulate that a chromosome change is the
primary cause of BMFS/AA in a not negligible proportion of cases, as it was
ascertained in 6 of these patients.
PMID- 29344090
TI - Overexpression of the proneural transcription factor ASCL1 in chronic lymphocytic
leukemia with a t(12;14)(q23.2;q32.3).
AB - Background: Translocations of the IGH locus on 14q32.3 are present in about 8% of
patients with chronic lymphocytic leukemia (CLL) and contribute to leukemogenesis
by deregulating the expression of the IGH-partner genes. Identification of these
genes and investigation of the downstream effects of their deregulation can
reveal disease-causing mechanisms. Case presentation: We report on the molecular
characterization of a novel t(12;14)(q23.2;q32.3) in CLL. As a consequence of the
rearrangement ASCL1 was brought into proximity of the IGHJ-CMU enhancer and was
highly overexpressed in the aberrant B-cells of the patient, as shown by qPCR and
immunohistochemistry. ASCL1 encodes for a transcription factor acting as a master
regulator of neurogenesis, is overexpressed in neuroendocrine tumors and a
promising therapeutic target in small cell lung cancer (SCLC). Its overexpression
has also been recently reported in acute adult T-cell leukemia/lymphoma.To
examine possible downstream effects of the ASCL1 upregulation in CLL, we compared
the gene expression of sorted CD5+ cells of the translocation patient to that of
CD19+ B-cells from seven healthy donors and detected 176 significantly
deregulated genes (Fold Change >=2, FDR p <= 0.01). Deregulation of 55 genes in
our gene set was concordant with at least two studies comparing gene expression
of normal and CLL B-lymphocytes. INSM1, a well-established ASCL1 target in the
nervous system and SCLC, was the gene with the strongest upregulation (Fold
Change = 209.4, FDR p = 1.37E-4).INSM1 encodes for a transcriptional repressor
with extranuclear functions, implicated in neuroendocrine differentiation and
overexpressed in the majority of neuroendocrine tumors. It was previously shown
to be induced in CLL cells but not in normal B-cells upon treatment with IL-4 and
to be overexpressed in CLL cells with unmutated versus mutated IGHV genes. Its
role in CLL is still unexplored. Conclusion: We identified ASCL1 as a novel IGH
partner gene in CLL. The neural transcription factor was strongly overexpressed
in the patient's CLL cells. Microarray gene expression analysis revealed the
strong upregulation of INSM1, a prominent ASCL1 target, which was previously
shown to be induced in CLL cells upon IL-4 treatment. We propose further
investigation of the expression and potential role of INSM1 in CLL.
PMID- 29344091
TI - The correlation between gain of chromosome 8q and survival in patients with clear
and papillary renal cell carcinoma.
AB - Background: The proto-oncogene c-MYC, located on chromosome 8q, can be
upregulated through gain of 8q, causing alteration in biology of renal cell
carcinoma (RCC). The aim of this study was to evaluate the prevalence of c-MYC
through chromosome 8q gain and to correlate findings with cancer-specific
mortality (CSM), and overall survival (OS). Methods: Cytogenetic analysis by
conventional or Chromosomal Genomic Microarray Analysis (CMA) was performed on
414 renal tumors. Nonclear and nonpapillary RCC were excluded. Impact of gain in
chromosome 8q status on CSM, OS, and its correlation with clinicopathological
variables were evaluated. CSM and OS were assessed using log-rank test and the
Cox proportional hazards model. Results: A total of 297 RCC tumors with
cytogenetic analysis were included. Gain of 8q was detected in 18 (6.1%) tumors
(9 clear cell and 9 papillary RCC), using conventional method (n = 11) or CMA (n
= 7). Gain of 8q was associated with higher T stage (p < 0.001), grade (p <
0.001), nodal involvement (p = 0.005), and distant metastasis (p < 0.001). No
association between gain of 8q and age (p = 0.23), sex (p = 0.46), and Charlson
comorbidity index (CCI, p = 0.59) were seen. Gain of 8q was associated with an
8.38-fold [95% confidence interval (CI), 3.83-18.34, p < 0.001] and 3.31-fold
(95% CI, 1.56-7.04, p = 0.001) increase in CSM and decrease in OS, respectively,
at a median follow up of 56 months. Conclusion: Chromosome 8q harbors the proto
oncogene c-MYC, which can be upregulated by gain of 8q. Our findings suggest that
gain of 8q, can predict aggressive tumor phenotype and inferior survival in RCC.
PMID- 29344092
TI - Engaging the primary care community to encourage appropriate prostate cancer
screening.
AB - Prostate-specific antigen (PSA) screening for prostate cancer remains a
controversial topic, particularly in the primary care community. Our
multidisciplinary prostate screening panel at Duke University Health System, USA
created a nuanced PSA screening algorithm, implemented it into the Electronic
Health Record of Duke Primary Care, and conducted outreach meetings with primary
care practices to support its rollout. Through this project, we identified areas
of concern among primary care clinicians regarding PSA screening that we
structured into two major categories: ideological opposition and logistical
opposition. We outlined specific concerns in each major category and described
how our team responded to those concerns. As communication between primary care
clinicians and prostate specialists is vital to the success and safety of PSA
screening programs, we hope that describing primary care concerns and our
responses to them will help other health systems thoughtfully and efficiently
implement appropriate PSA screening programs moving forward.
PMID- 29344093
TI - Current best practice in the management of cystitis and pelvic pain.
AB - Bladder pain syndrome (BPS) is a difficult disorder to diagnose and subsequently
manage despite having been recognized for more than 200 years according to
references in medical literature. There are currently three widely accepted
guidelines on BPS: the American Urological Association Guidelines; the Royal
College of Obstetricians and Gynaecologists in conjunction with the British
Society of Urogynaecologists Guidelines; and the European Association of Urology
Guidelines. These guidelines have similarities to each other but also significant
differences. This leaves clinicians still confused about this condition and how
to appropriately manage the 'real' patient. We review the current guidelines and
appropriate literature and put forward a clinically usable management strategy.
PMID- 29344094
TI - Robotic prostatectomy leading to a delayed MRSA infected lymphocele: a case
report and review of the literature.
AB - Prostate cancer is the second leading cancer-related cause of death in the USA
with the majority presenting as localized disease. In the last decade minimally
invasive, robotic-assisted laparascopic, radical prostatectomy has become the
most favored treatment choice. A complication that has been observed in 27% of
patients is the formation of an asymptomatic lymphocele. It is a very rare
complication for these to become infected, and when they do 80% have occurred 2
12 months post-procedure. In this case report the patient presented with fever
and leukocytosis of unknown origin and was found to have a methicillin-resistant
Staphylococcus aureus (MRSA) infected lymphocele over 2 years after a radical
prostatectomy. The infected fluid collection was drained percutaneously and the
patient was treated with a 4-week course of intravenous ceftaroline with complete
resolution of symptoms.
PMID- 29344095
TI - Metachronous metastasis of renal cell carcinoma to the urinary bladder: a case
report.
AB - We report a case of intravesical metastasis of a clear cell renal cell carcinoma.
In renal cell carcinoma 16% of patients present with metastatic disease. Renal
cell carcinoma can metastasize to nearly every organ, although metastatic spread
to the urinary bladder is rare, with fewer than 70 described cases. The route and
pattern of metastatic spread is not yet fully understood and different pathways
are suggested. Gross haematuria is the presenting symptom in the majority of
cases. These intravesical metastases may be synchronous or metachronous and can
be solitary or part of polymetastatic disease. No standard treatment can be
suggested due to the rare nature of this phenomenon, and treatment varies from
transurethral resection, partial or complete cystectomy to systemic therapy.
Prognosis in patients with a solitary bladder lesion that developed
metachronously is rather good, whereas poor prognosis can be expected in patients
with synchronous and multiple metastases.
PMID- 29344096
TI - Prevention is better than cure: The role of infection prevention in the control
of antimicrobial resistance.
PMID- 29344097
TI - Investigating the use of an electronic hand hygiene monitoring and prompt device:
influence and acceptability.
AB - Introduction: Hand hygiene (HH) prevents the transmission of healthcare
associated infections. Electronic HH monitoring and prompt devices have been
developed to overcome problems with monitoring HH and to improve compliance.
Devices monitor room entry and exit and soap use through communication between
ceiling sensors and badges worn by practitioners and the badges sense alcohol
rub. Objectives: To investigate (1) the impact of devices on HH compliance, (2)
how devices influence behaviour and (3) the experience and opinions of
practitioners on the use devices. Methods: HH compliance was monitored (before,
during and after system installation) by observations and alcohol rub usage.
Compliance during installation was also monitored by the device. Healthcare
practitioner interviews (n = 12) explored how the device influenced behaviour and
experiences and opinions of wearing the device. Results: HH compliance improved
during the period the device was installed. Practitioners reported the device
increased their awareness, enhancing their empathy for patients and encouraged
patients and colleagues to prompt when HH was needed. Practitioners' reported
better HH, gaming the system and feelings of irritation. Conclusion: HH prompt
and monitoring systems seem to improve compliance but improvements may be
undermined by practitioner irritation and system gaming.
PMID- 29344098
TI - 'Time to clean': A systematic review and observational study on the time required
to clean items of reusable communal patient care equipment.
AB - Background: Concerns have been raised over poor standards of hospital cleanliness
and insufficient time for staff to clean reusable communal patient care
equipment. These items may then act as vectors for the transmission of nosocomial
pathogens between hospital patients. Aim: To evaluate the impact of cleaning
duration on nosocomial infection rates and estimate the time required to clean
care equipment in accordance with national specifications (i.e. a 'time to
clean'). Methods: A systematic review of the published literature on cleaning
times and an observational study in which nine healthcare workers cleaned seven
items of care equipment while the duration of time taken to clean each item was
measured. Results: A limited volume of low-quality evidence indicates that
increased cleaning times in hospitals can reduce the incidence of healthcare
associated infections (HCAIs). The mean 'time to clean' for care equipment ranged
from 166.3 s (95% confidence interval [CI] = 117.8-214.7) for a bed frame to 29.0
s (95% CI = 13.4-44.6) for a blood pressure cuff. Discussion: 'Time to clean'
estimates for care equipment provide an indication of how much protected time is
necessary to ensure acceptable standards of cleanliness. Clinical trials are
needed to further evaluate the impact of increased cleaning times on nosocomial
infection rates.
PMID- 29344099
TI - Audit of the management of patients at high risk of carbapenemase-producing
enterobacteriaceae (CPE): Are we ready?
AB - Background: Incidence of carbapenemase-producing enterobacteriaceae (CPE) in the
UK is increasing. In 2013, Public Health England (PHE) published a toolkit to
control spread of CPE within healthcare settings. Aim: To assess compliance to
hospital CPE policy (adapted from PHE) in the identification, isolation and
screening of suspected CPE patients. Methods: Admission booklets of 150 patients
were evaluated to see whether the relevant section had been completed to identify
high-risk CPE patients. Where necessary, patients were interviewed or their GPs
were contacted to assess their CPE risk. Additionally, 28 patients screened for
CPE were audited to assess compliance to screening and isolation. Findings: Only
23 patients out of 147 (15.6%) were risk assessed on admission. Risk status of 27
(18.4%) patients could not be assessed due to lack of data. Fifteen patients out
of 28 (54%) screened for CPE were identified and isolated on admission. Ten out
of 19 patients (53%) had three screens 48 h apart. Discussion: This audit
highlights difficulties in screening based on individual risk factors as the
majority of patients were not screened on admission and documentation on
isolation and screening was poor. More needs to be done to raise awareness of the
requirements for routine assessment, isolation and screening.
PMID- 29344100
TI - Surgical site infection prevention: An analysis of compliance with good practice
in a teaching hospital.
AB - Background: Surgical teams play a critical role in reducing surgery-related risks
during preoperative and intraoperative phases. Aim: To analyse the preoperative
and intraoperative practices adopted by surgical teams in surgical site
infections prevention. Methods: This was a cross-sectional study conducted during
April-September 2013 in a large university hospital in Belo Horizonte, Minas
Gerais, Brazil. It was conducted through observation of the surgical practice
during preoperative and intraoperative phases of procedures used by a
gastroenterological, cardiovascular and paediatric surgical team. Results: A
total of 100 surgeries were monitored. Hair removal was performed for 20% of the
patients inside the operating room by professionals using clippers in 65% of
operations. The antimicrobial agent of choice was appropriate/satisfactory in 62%
of the operations and administered up to 60 min before surgical incision in 90.3%
of the cases. The operating room door was kept closed in 4% of these procedures.
Discussion: Some preoperative measures for surgical site infection prevention
were not adhered to by the professionals who were monitored in this study. It is
recommended that surgical teams undergo professional surveillance and training to
highlight the necessity and importance of implementing measures to improve the
quality of care provided to surgical patients.
PMID- 29344101
TI - Healthcare-associated Legionnaires' disease: Limitations of surveillance
definitions and importance of epidemiologic investigation.
AB - Healthcare-associated Legionnaires' disease (HCA LD) causes significant morbidity
and mortality, with varying guidance on prevention. We describe the evaluation of
a case of possible HCA LD and note the pitfalls of relying solely on an
epidemiologic definition for association of a case with a facility. Our detailed
investigation led to the identification of a new Legionella pneumophila serogroup
1 sequence type, confirmed a healthcare association and helped build the
framework for our ongoing preventive efforts. Our experience highlights the role
of routine environmental cultures in the assessment of risk for a given facility.
As clinicians increasingly rely on urinary antigen testing for the detection of
L. pneumophila, our investigation emphasises the importance of clinical cultures
in an epidemiologic investigation.
PMID- 29344103
TI - Diary.
PMID- 29344102
TI - Should preoperative showering or cleansing with chlorhexidine gluconate (CHG) be
part of the surgical care bundle to prevent surgical site infection?
AB - Showering preoperatively with chlorhexidine gluconate is an issue that continues
to promote debate; however, many studies demonstrate evidence of surgical site
infection risk reduction. Methodological issues have been present in many of the
studies used to compile guidelines and there has been a lack of standardisation
of processes for application of the active agents in papers pre-2009. This review
and commentary paper highlights the potential for enhancing compliance with this
low-risk and low-cost intervention and provides some guidance for enhancing
implementation of preoperative showering with both chlorhexidine in solution and
impregnated wipes.
PMID- 29344104
TI - X-inactive-specific transcript of peripheral blood cells is regulated by exosomal
Jpx and acts as a biomarker for female patients with hepatocellular carcinoma.
AB - Background: Long noncoding ribonucleic acid (lncRNA) X-inactive-specific
transcript (Xist) was reported to affect cell proliferation and metastasis in
hepatocellular carcinoma (HCC). However, there are rare reports focusing on the
diagnostic evaluation and regulatory mechanism of Xist expression from peripheral
blood cells of patients with HCC. Methods: In this study, a cohort of 206 female
participants including healthy volunteers (HVs) and patients with chronic
hepatitis B (CHB), cirrhosis and HCC was recruited. Coculture system was used to
evaluate the effects of exosomal JPX transcript, XIST activator (Jpx) on Xist
expression of blood cells. Results: First, Xist expressions of both peripheral
blood mononuclear cells and granulocytes were upregulated in female patients with
HCC, and showed significantly increased discriminatory power when differentiating
female patients with early-stage HCC from controls or differentiating female
patients with HCC from patients with CHB and cirrhosis, compared with alpha
fetoprotein (AFP). Then, another lncRNA Jpx that was an activator of Xist was
upregulated in exosomes, mononuclear cells and granulocytes of female patients
with HCC. Furthermore, our results showed that Jpx could be delivered from HCC
cells to blood cells via exosomes and activate Xist expression of blood cells by
repressing the transregulatory effects of CCCTC-binding factor (CTCF).
Conclusions: This study revealed an exosome-mediated regulation of Xist
expression in blood cells and suggested that Xist expressions of mononuclear
cells and granulocytes would be promising biomarkers for diagnosis of female
patients with HCC.
PMID- 29344105
TI - Optimal duration of adjuvant endocrine therapy: how to apply the newest data.
AB - Background: The benefit of 5 years of adjuvant endocrine therapy for women with
hormone receptor-positive (HR+) breast cancer (BC) is beyond discussion.
Nevertheless, the risk of recurrence of luminal BC persists for 15 years or more
after diagnosis. Consequently, approaches of extended adjuvant therapy have been
investigated in large clinical trials, with the ultimate aim of further reducing
the risk of recurrence in patients with HR+ BC. Methods: A review of recently
published trial data is presented to provide a solid basis for discussion. A
discussion of the side effects of long-term endocrine treatment, multigenetic
tests aiming to identify patients at particular risk, and an outlook for further
promising targets are additional aims of this review. Conclusion: Extended
adjuvant therapy seems beneficial in reducing distant relapse and contralateral
BC for a selected group of patients with HR+ BC, particularly if aromatase
inhibitors (AIs) are used after initial tamoxifen therapy. However, patients with
lower risk of recurrence and initial AI therapy may suffer more from side effects
than benefit from extended therapy.
PMID- 29344106
TI - Overall survival and progression-free survival with endocrine therapy for hormone
receptor-positive, HER2-negative advanced breast cancer: review.
AB - We reviewed randomized phase II/III trials comparing first- or second-line
endocrine therapy as monotherapy or in combination with targeted therapies for
treatment of postmenopausal patients with hormone receptor-positive advanced
breast cancer. First-line was defined as treatment for endocrine therapy-naive
advanced breast cancer or advanced disease treated with endocrine therapy in the
adjuvant/neoadjuvant setting. Second-line was defined as endocrine therapy for
advanced breast cancer following disease progression on endocrine therapy for
advanced disease. Publications reporting progression-free survival (PFS)/time to
progression (TTP) or overall survival (OS) for FDA-approved agents anastrozole,
exemestane, fulvestrant 250 mg, fulvestrant 500 mg, letrozole (0.5 and 2.5 mg),
megestrol acetate, and tamoxifen as monotherapy, or in combination with
everolimus, palbociclib or ribociclib, were assessed. First-line monotherapy with
anastrozole, fulvestrant 500 mg or letrozole 2.5 mg significantly improved
PFS/TTP versus comparator endocrine therapy; however, only fulvestrant 500 mg
improved OS. For endocrine therapy in combination with targeted therapies,
palbociclib plus letrozole 2.5 mg, and ribociclib plus letrozole 2.5 mg
significantly improved PFS versus letrozole 2.5 mg alone first-line. For second
line monotherapies, exemestane, fulvestrant 500 mg and letrozole 2.5 mg
significantly improved PFS/TTP versus comparator endocrine therapy; only
fulvestrant 500 mg and letrozole 2.5 mg improved OS. For second-line combination
therapies, everolimus plus exemestane, and palbociclib plus fulvestrant 500 mg,
improved PFS versus endocrine therapy alone. In both first- and second-line
settings, aromatase inhibitors demonstrated PFS benefits versus comparator
endocrine therapy; however, fulvestrant 500 mg was the only endocrine therapy
included in our review to show both PFS and OS advantages compared with other
endocrine therapies. Targeted agents in combination with endocrine therapy have
demonstrated PFS improvements both first- and second-line; OS data are awaited.
PMID- 29344107
TI - Managing hyponatremia in lung cancer: latest evidence and clinical implications.
AB - Hyponatremia is the most common electrolyte disorder in lung cancer patients.
This condition may be related to many causes including incidental medications,
concurrent diseases and side effects of antineoplastic treatments or the disease
itself. Although not frequently life-threatening, it is usually associated with
prolonged hospitalization, delays in scheduled chemotherapy, worsening of patient
performance status and quality of life and may also negatively affect treatment
response and survival. Most of the available data focus on thoracic tumors,
especially small-cell lung cancer (SCLC), where hyponatremia is frequently
related to the syndrome of inappropriate secretion of antidiuretic hormone
(SIADH). Few studies specifically focus on non-small cell lung cancer (NSCLC)
patients. Hyponatremia treatment needs to be personalized based on severity and
duration of sodium serum reduction, extracellular fluid volume and etiology.
However, literature data highlight the importance of early correction of the
serum concentration levels. To achieve this the main options are fluid
restriction, hypertonic saline, loop diuretics, isotonic saline, tolvaptan and
urea. The aim of this review is to analyze the role of hyponatremia in lung
cancer patients, evaluating causes, diagnosis, management and clinical
implications.
PMID- 29344109
TI - Corrigendum.
AB - [This corrects the article DOI: 10.1177/1758834017711097.].
PMID- 29344108
TI - Estimating the 95% confidence interval for survival gain between an experimental
anti-cancer treatment and a control.
PMID- 29344111
TI - Corrigendum.
AB - [This corrects the article DOI: 10.1177/1759720X17729641.].
PMID- 29344110
TI - Anti-interleukin and interleukin therapies for psoriasis: current evidence and
clinical usefulness.
AB - Anti-interleukin (IL) therapies have emerged as a major treatment for patients
with moderate-to-severe psoriasis. This article reviews the up-to-date results of
pivotal clinical trials targeting the interleukins used for the treatment of
psoriasis, including IL-1, IL-2, IL-6, IL-8, IL-10, IL-12, IL-17, IL-20, IL-22,
IL-23, IL-36 and bispecific biologics IL-17A/tumor necrosis factor alpha (TNF
alpha). Cytokines involved in the circuits of psoriasis inflammation without
ongoing clinical trials are also mentioned (IL-9, IL-13, IL-15, IL-16, IL-18, IL
19, IL-21, IL-24, IL-27, IL-33, IL-35, IL-37, and IL-38).
PMID- 29344112
TI - ZGDHu-1 for cancer therapy.
AB - N,N'-di-(m-methylphenyl)-3,6-dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4
dicarboamide (ZGDHu-1) is a novel tetrazine derivative that was initially
designed and produced by Professor W.X. Hu, and which has been reported by our
group to exhibit antitumor activity. Accumulating evidence suggests that the
anticancer mechanisms of ZGDHu-1 may be involved indifferent biological
activities, particularly in acute myeloid leukemia (AML) cells. At a high
concentration, ZGDHu-1 has been demonstrated to inhibit the proliferation of the
leukemia cells by arresting the cell cycle at the G2/M phase, and by inducing
cell apoptosis via inducing the accumulation of reactive oxygen species, the
translocation of phosphatidylserine across the plasma membrane and the loss of
mitochondrial membrane potential. Furthermore, at a low concentration, it was
demonstrated to induce the differentiation and degrade the AML1-eight-twenty-one
fusion protein in AML cells. Finally, results from a previous study indicate that
ZGDHu-1 is a potential proteasome inhibitor. Overall, our preliminary research
suggests that ZGDHu-1 may be a promising anticancer drug; however, further
research is warranted to identify the exact drug target and potential clinical
application in leukemia cells or solid tumors. In the present review, the
application of ZGDHu-1 in cancer research, in addition to the specific underlying
targets of ZGDHu-1, are discussed.
PMID- 29344113
TI - Downregulated miRNA-1269a variant (rs73239138) decreases the susceptibility to
gastric cancer via targeting ZNF70.
AB - Although emerging evidence has indicated that single nucleotide polymorphisms
(SNPs) in microRNAs (miRNAs) are associated with susceptibility to gastric
cancer, a limited number of studies have revealed the underlying molecular
mechanisms. In the present study, the results suggested that miR-1269a rs73239138
has a role in decreasing the risk of gastric cancer. The level of miR-1269a
variant expression was significantly downregulated compared with the wild-type
miR-1269a in the gastric cells (Fig. 1). Furthermore, overexpression of miR-1269a
inhibited apoptosis of gastric cancer cells. Expression of the miR-1269a variant
inhibited the function of miR-1269a by increasing the apoptotic rate and the
expression of Bik, Bim and Bak was upregulated consistently. In addition, zinc
finger protein 70 (ZNF70) was identified to be a target gene of miR-1269a, which
was downregulated by miR-1269a and upregulated by miR-1269a variant. ZNF70 was
indicated to exert a role as a tumor suppressor in gastric cancer. To the best
our knowledge, the present study for the first time highlights a critical role of
miR-1269a variant rs73239138 in decreasing the susceptibility to gastric cancer
by downregulating its expression and targeting ZNF70, which promotes apoptosis of
gastric cancer cells. This SNP is indicated to serve as a potential biomarker and
therapeutic target for gastric cancer.
PMID- 29344114
TI - HNF-4alpha promotes multidrug resistance of gastric cancer cells through the
modulation of cell apoptosis.
AB - Multidrug resistance (MDR) typically leads to treatment failure, and is
associated with disease progression of gastric cancer (GC). In the present study,
a total of 15 aberrantly activated transcription factors (TFs) were detected in
chemo-resistant GC cells using a TF Activation Profiling Plate Array. Among these
TFs, hepatocyte nuclear factor (HNF)-4alpha was significantly upregulated in
multidrug-resistant GC cells (P=0.019). The overexpression of HNF-4alpha was able
to cause resistance to multiple chemotherapeutics, whereas inhibition of HNF
4alpha appeared to reverse cancer cell resistance. Further studies demonstrated
that HNF-4alpha had no clear influence on drug transportation; however,
inhibition of drug-induced cell apoptosis occurred as B-cell lymphoma 2 (Bcl-2)
expression increased in GC cells. Additionally, immunohistochemistry demonstrated
that HNF-4alpha was overexpressed in human GC tissues, and associated with tumor
stage and lymph node metastasis. In conclusion, the results of the present study
indicate the involvement of TFs in MDR in GC, and suggest that HNF-4alpha may
enhance MDR in GC by regulating cell apoptosis and Bcl-2 expression.
PMID- 29344115
TI - Clinical significance of LMO1 in gastric cancer tissue and its association with
apoptosis of cancer cells.
AB - It has been reported that LMO1 gene was associated with progression, metastasis
and apoptosis of leukemia, colorectal cancer and lung cancer. However, the
association of LMO1 and gastric cancer remains unclear. The aim of this study is
to analyze the relation between LMO1 expression and apoptosis of gastric cancer
cells and explore the clinical implications of LMO1 in gastric cancer tissues.
The results demonstrated that expression levels of LMO1 and Bcl-2 proteins in
gastric cancer tissues were higher than those in adjacent tissues, whereas the
opposite was detected for Bax expression (P<0.05). LMO1 protein was associated
with TNM staging and lymph node metastasis in gastric cancer (P<0.05). The
survival rate of the patients with positive LMO1 gastric carcinoma was lower than
that with negative LOM1 expression, and LMO1 was as an independent prognostic
factor in COX survival analysis (P<0.05). LMO1-siRNA transfected MKN45 cells had
a significant decrease in LMO1 expression and the cell viability, despite of an
increase in the apoptotic rate (P<0.05). Following LMO1-siRNA transfection, Bcl-2
expression decreased, while the expression of Bax increased (P<0.05). It's
concluded that overexpressed LMO1 in gastric cancer could be as one of new
markers of poor prognosis.
PMID- 29344116
TI - Knockdown of TGIF attenuates the proliferation and tumorigenicity of EC109 cells
and promotes cisplatin-induced apoptosis.
AB - A previous study has reported that frequent amplifications of the TG-interacting
factor (TGIF) were observed in esophageal squamous cell carcinoma. The aim of the
present study was to investigate the potential role of TGIF in the proliferation
and tumorigenicity of the esophageal cancer cell line EC109 and cisplatin-induced
apoptosis. Stable TGIF-knockdown EC109 cell line was established by infecting
short hairpin RNA (shRNA) lentiviral particles. Soft agar and tumor xenograft
assays were applied in nude mice. Flow cytometry was employed to evaluate the
cell cycle and apoptosis. Western blot analysis was used to detect the expression
of proteins. TGIF knockdown suppressed EC109 cell proliferation, colony formation
in soft agar and tumor growth in nude mice, induced cell cycle arrest in the G1
phase, and promoted cisplatin-induced apoptosis. In addition, TGIF knockdown
significantly reduced the expression of phospho-Rb in EC109 cells. The reduced
level of full length PARP expression and the increased level of cleaved caspase-3
expression were observed in EC109 cells with the treatment of cisplatin and TGIF
knockdown. The results suggest that knockdown of TGIF attenuated the
proliferation and tumorigenicity of EC109 cells, and promoted cisplatin-induced
apoptosis.
PMID- 29344117
TI - Wnt inhibitor XAV939 suppresses the viability of small cell lung cancer NCI-H446
cells and induces apoptosis.
AB - Small cell lung cancer (SCLC) is the most aggressive type of lung cancer due to a
fast tumor doubling time and early hematogenous spread. Advances in the treatment
of non-small cell lung cancer using targeted therapies having been made, but no
targeted drugs for SCLC have been approved. The Wnt signaling pathway is
associated with tumor progression and metastasis; therefore, the inhibition of
Wnt/beta-catenin signaling is a strategy for anticancer drugs. Tankyrase 1
(TNKS1) is overexpressed in a number of types of cancer and XAV939 is a small
molecule inhibitor of TNKS1 which may inhibit tumor growth. The present study
aimed to investigate the potential molecular mechanisms underlying XAV939-induced
suppression of the viability of SCLC cells. MTT assays were used to determine the
viability-inhibition rate of cells and to identify the drug concentration which
optimally inhibited cell viability. Flow cytometry was used to determine whether
XAV939 induced apoptosis of SCLC cells, and to analyze the effect of the drug on
the cell cycle. The results of the present study identified that XAV939 inhibited
the viability of NCI-H446 cells in a dose-dependent manner, but cisplatin
inhibited NCI-H446 cell viability in a time- and dose-dependent manner. The
combination of XAV939 and cisplatin exhibited a slightly more pronounced
inhibition of cell viability at an increased dose of XAV939. In addition, XAV939
markedly induced cell apoptosis of the SCLC cell line H446 by increasing the
proportion of cells in the G0/G1 phase, leading to inhibition of the cell cycle.
The results of the present study indicated that XAV939 inhibited the viability of
the NCI-H446 SCLC cell line by inducing cell apoptosis through the Wnt signaling
pathway. Therefore, XAV939 may be useful for the treatment of SCLC.
PMID- 29344118
TI - SHISA2 enhances the aggressive phenotype in prostate cancer through the
regulation of WNT5A expression.
AB - The present study aimed at identifying novel molecular cancer drug targets and
biomarkers by analyzing the gene expression profiles of high-grade prostate
cancer (PC), using a cDNA microarray combined with laser microbeam
microdissection. A number of genes were identified that were transactivated in
high-grade PC. First, a novel molecular target and diagnostic biomarker, shisa
family member 2 (SHISA2), was identified as an overexpressed gene in high-grade
PC cells. The reverse transcription-semi-quantitative polymerase chain reaction
and immunohistochemical analysis validated the overexpression of SHISA2 (295
amino acids in length), specifically in high-grade PC cells with Gleason scores
of between 8 and 10, relative to normal prostate epithelium. Knockdown of SHISA2
expression by short interfering RNA resulted in the marked suppression of PC cell
viability. By contrast, exogenous SHISA2 expression in transfected cells promoted
PC cell proliferation, indicating its oncogenic effects. Notably, as a result of
cDNA microarray analysis, protein Wnt-5a (WNT5A) was focused upon and the
expression of WNT5A was identified to be downregulated in SHISA2-knockdown.
Western blot analysis validated significant downregulation of WNT5A by SHISA2
knockdown and upregulation of WNT5A by SHISA2 overexpression. The results of the
present study indicated that SHISA2 may affect WNT5A synthesis. Furthermore, the
secreted SHISA2 protein was determined in the culture medium of PC cells. We
hypothesize that SHISA2 is involved in the regulation of WNT5A and in the
aggressiveness of PC via the Wnt signaling pathway through WNT5A. Furthermore,
SHISA2 may be a molecular target for cancer drugs, and a useful diagnostic
biomarker for the prognosis and therapeutic effect in cancer.
PMID- 29344119
TI - Effect of Lipodox in combination with bevacizumab in a patient with a metastatic
malignant phyllodes breast tumor: A case report.
AB - A 76-year-old female patient with a malignant phyllodes tumor underwent modified
radical mastectomy and wide excision. Multiple nodules were observed in the
operated wound area. Positron emission tomography-computed tomography (PET-CT)
revealed recurrent disease in the left breast, the adjacent left third rib, the
left internal mammary region and the left ilium. A novel formulation of
bevacizumab (5 mg/m2, first day) in combination with liposomal doxorubicin
(Lipodox, 30 mg/m2, second day) was administered for 3 cycles every 2 weeks, and
subsequently wide excision was performed. Lipodox (40 mg/m2) was administered for
3 cycles every 3 weeks, starting 4 weeks after the surgery. Follow-up whole body
PET-CT scanning, 3 and 6 months later, indicated no sign of residual
hypermetabolic malignancy. Malignant phyllodes tumors do not usually respond to
chemotherapy or radiotherapy. In the present case report, a novel formulation of
bevacizumab in combination with Lipodox was administered as neoadjuvant
chemotherapy in a patient with a malignant phyllodes tumor and preoperative tumor
shrinkage was achieved, resulting in clear resection margins.
PMID- 29344120
TI - Interim 18F-FDG PET/CT improves the prognostic value of S-IPI, R-IPI and NCCN-IPI
in patients with diffuse large B-cell lymphoma.
AB - The current study aimed to explore whether the efficiency of the standard
International Prognostic Index (S-IPI), revised-IPI (R-IPI) and enhanced-IPI
(NCCN-IPI) in evaluating the prognosis of patients with diffuse large B-cell
lymphoma (DLBCL) may be improved by interim 18F-FDG PET/CT. A total of 185
patients with newly diagnosed DLBCL were enrolled in the current study. All
patients underwent interim PET/CT following the 4th cycle of chemotherapy.
Patients were divided into different risk groups using S-IPI, R-IPI and NCCN-IPI
and further subdivided into risk groups using interim PET/CT. Interpretations
were evaluated for 2-year progression-free survival (PFS) and overall survival
(OS). With a median follow-up time of 44 months, the 2-year PFS and OS were 60%
[95% confidence interval (CI) 53-67%] and 81% (95% CI 74-86%), respectively.
Analysis of S-IPI and NCCN-IPI identified no significant difference in PFS and OS
between high intermediate and high risk groups. However, there were significant
differences in the PFS and OS between the low and low intermediate risk groups
(P<0.01). Interim PET/CT was used to redistribute patients in the higher risk
group into PET negative and positive groups (P<0.01) and arallel results were
observed in the lower risk group. In R-IPI, interim PET/CT identified a
significant difference between PFS and OS in the good and poor risk groups but
not in the very good risk group. Therefore, the results of the current study
indicate that S-IPI, R-IPI and NCCN-IPI are three clinically useful prognostic
indexes for patients with DLBCL. Interim PET/CT may improve the prognostic value
of S-IPI, R-IPI and NCCN-IPI in predicting 2-year PFS and OS, particularly in
patients with a high IPI score.
PMID- 29344121
TI - A five-gene based risk score with high prognostic value in colorectal cancer.
AB - Colorectal cancer (CRC) is one of the most frequently occurring malignancies
worldwide. The outcomes of patients with similar clinical symptoms or at similar
pathological stages remain unpredictable. This inherent clinical diversity is
most likely due to the genetic heterogeneity. The present study aimed to create a
predicting tool to evaluate patient survival based on genetic profile. Firstly,
three Gene Expression Omnibus (GEO) datasets (GSE9348, GSE44076 and GSE44861)
were utilized to identify and validate differentially expressed genes (DEGs) in
CRC. The GSE14333 dataset containing survival information was then introduced in
order to screen and verify prognosis-associated genes. Of the 66 DEGs, the
present study screened out 46 biomarkers closely associated to patient overall
survival. By Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway
analysis, it was demonstrated that these genes participated in multiple
biological processes which were highly associated with cancer proliferation, drug
resistance and metastasis, thus further affecting patient survival. The five most
important genes, MET proto-oncogene, receptor tyrosine kinase, carboxypeptidase
M, serine hydroxymethyltransferase 2, guanylate cyclase activator 2B and sodium
voltage-gated channel a subunit 9 were selected by a random survival forests
algorithm, and were further made up to a linear risk score formula by
multivariable cox regression. Finally, the present study tested and verified this
risk score within three independent GEO datasets (GSE14333, GSE17536 and
GSE29621), and observed that patients with a high risk score had a lower overall
survival (P<0.05). Furthermore, this risk score was the most significant compared
with other predicting factors including age and American Joint Committee on
Cancer stage, in the model, and was able to predict patient survival
independently and directly. The findings suggest that this survival associated
DEGs-based risk score is a powerful and accurate prognostic tool and is
promisingly implemented in a clinical setting.
PMID- 29344122
TI - Inhibition of breast cancer cell growth by the Pteris semipinnata extract ent
11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid.
AB - Previous studies have demonstrated strong anti-tumor effects of ent-11alpha
hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F), an extract from Pteris semipinnata,
in liver, lung, stomach and anaplastic thyroid cancer cells. However, whether 5F
inhibits the growth of breast cancer cells remains unclear. The present study
assessed the effect of 5F on breast cancer cells. The breast cancer cell lines
MCF-7, MDA-MB-231 and SK-BR-3 were each treated with 0, 5, 10, 20 and 40 ug/ml
5F. Morphological changes in the breast cancer cells were assessed using
fluorescence microscopy. The proliferation and apoptosis of the breast cancer
cells were also examined using Cell Counting Kit-8 and flow cytometry. The levels
of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X apoptosis regulator (Bax), Bcl-2
antagonist/killer (Bak) 1 and caspase-3 in the breast cancer cells were assessed.
The results of the present study demonstrated that 5F inhibited the proliferation
of MCF-7, MDA-MB-231 and SK-BR-3 breast cancer cells in a concentration- and time
dependent manner. Treatment with 5F also induced the apoptosis of breast cancer
cells. MDA-MB-231, MCF-7, and SK-BR-3 cells exhibited apoptotic rates of 40.13,
60.44, and 70.49%, respectively, following incubation with 5F for 24 h.
Furthermore, 5F significantly decreased the expression of Bcl-2 and increased the
expression of Bax, Bak, and caspase-3 in a concentration-dependent manner. The
results of the present study revealed that the P. semipinnata extract 5F
inhibited the growth of human breast cancer cells in a time- and concentration
dependent manner, and that 5F induced apoptosis of human breast cancer cells.
PMID- 29344123
TI - Ex vivo model of non-small cell lung cancer using mouse lung epithelial cells.
AB - Lung cancer is the most common cause of cancer mortality, however, efficient
methods to culture, expand and transform lung epithelial (LE) cells have not been
established. In the present study, an efficient ex vivo method was applied to
recapitulate lung carcinogenesis using mouse LE cells. A Matrigel-assisted three
dimensional culture was used to isolate and selectively expand LE cells from
mouse lungs. Purified LE cells were passaged and expanded for at least 2 to 3
months while maintaining epidermal growth factor-dependence. LE cells were also
easily transformed by genetic manipulations using retroviral vectors. A SV40
large-T antigen, suppressing p53 and pRB, plus an activated oncogene, such as
KrasG12V or EGFRex19del, were required to transform LE cells. Transformed cells
formed tumors resembling non-small cell lung cancer (NSCLC) in allograft models
and exhibited strong oncogene addiction. This experimental system provided a
unique model system to study lung tumorigenesis and develop novel therapeutics
against NSCLC.
PMID- 29344124
TI - Molecular, biological characterization and drug sensitivity of chidamide
resistant non-small cell lung cancer cells.
AB - Chidamide, a histone deacetylase (HDAC) inhibitor, has been applied in clinical
trials for various types of hematological and solid tumors. Although acquired
resistance is common in chemotherapy, the mechanism of resistance to chidamide is
poorly characterized. The goal of the present study was to explore, in detail,
the mechanism for the induced resistance to chidamide, and investigate a
potential cross-resistance to other chemotherapeutic drugs. A549 cells were
exposed to gradually increasing chidamide concentrations to establish a chidamide
resistant non-small cell lung cancer cell line (A549-CHI-R). The IC50 for
chidamide, the proliferation inhibition rate, the total HDAC activity and the
HDAC protein level were determined by an MTT assay, colony formation, a
fluorometric HDAC activity assay and western blotting, respectively.
Overexpression of the HDAC1 gene and HDAC1 gene-knockdown were achieved via
plasmid transfection. A549-CHI-R cells demonstrated increased resistance to
chidamide (8.6-fold). HDAC1 protein degradation was inhibited and HDAC activity
was significantly higher in the A549-CHI-R cells relative to the parental A549
cells. A549-CHI-R cells demonstrated cross-resistance to paclitaxel, vinorelbine
and gemcitabine, but not to cisplatin (CDDP) or 5-fluorouracil (5-FU). These
results indicated that HDAC1 may be associated with resistance to chidamide, and
HDAC1 may therefore be a predictive marker for chidamide sensitivity in cancer.
In addition, A549-CHI-R cells remained sensitive to 5-FU and CDDP, indicating a
potential strategy for cancer therapy.
PMID- 29344125
TI - miR-145-5p inhibits epithelial-mesenchymal transition via the JNK signaling
pathway by targeting MAP3K1 in non-small cell lung cancer cells.
AB - Lung cancer is one of the most common types of tumors and the leading cause of
cancer-associated mortality in the world. Additionally, non-small cell lung
cancer (NSCLC) accounts for ~80% of all lung cancer cases. Epithelial-mesenchymal
transition (EMT) is an important cell biological process, which is associated
with cancer migration, metastasis, asthma and fibrosis in the lung. In the
present study, it was revealed that miR-145-5p was able to suppress EMT by
inactivating the c-Jun N-terminal kinase (JNK) signaling pathway in NSCLC cells.
Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) was predicted and
confirmed to be a novel target of miR-145-5p. Overexpression of MAP3K1 was able
to reverse the inhibition of EMT induced by miR-145-5p via the JNK signaling
pathway. Overall, the results revealed that miR-145-5p inhibits EMT via the JNK
signaling pathway by targeting MAP3K1 in NSCLC cells.
PMID- 29344126
TI - microRNA-34a overexpression inhibits cell migration and invasion via regulating
SIRT1 in hepatocellular carcinoma.
AB - Hepatocellular carcinoma (HCC) remains one of the most common types of malignancy
with high mortality and morbidity rates. Previous studies have suggested that
microRNAs (miRs) serve pivotal functions in various types of tumor. The aim of
the present study was to assess the association between miR-34a expression and
HCC cell migration and invasion, and the potential underlying mechanisms. The miR
34a overexpression vector or scramble control was transfected into human Hep3B
and Huh7 cell lines. Transwell assays, and Matrigel and wound healing assays were
used to detect the effects of miR-34a expression on HCC cell invasion and
migration, respectively. The expression of miR-34a and the mRNA expression of
other associated proteins were detected using quantitative reverse transcription
polymerase chain reaction, and protein levels were measured using western blot
analysis. Compared with the control, miR-34a expression was significantly
downregulated in Hep3B and Huh7 cells, but this was reversed by the transfection
with exogenous miR-34a (P<0.01). The number of migrated or invaded cells was
significantly reduced by the overexpression of miR-34a in Hep3B or Huh7 cells
(P<0.01). The expression of sirtuin 1 was upregulated, while the level of
acetylate-p53 was downregulated by overexpression of miR-34a. Taken together, the
results of the present study suggested that the overexpression of miR-34a may
have suppressed HCC metastasis via inhibited cell migration and invasion.
PMID- 29344127
TI - Mechanisms of peritoneal dissemination in gastric cancer.
AB - Peritoneal dissemination is the most frequent metastatic pattern of gastric
cancer, but the mechanisms underlying peritoneal dissemination are yet to be
elucidated. Paget's 'seed and soil' hypothesis is recognized as the fundamental
theory of metastasis. The 'seeding' theory proposes that the formation of
peritoneal dissemination is a multistep process, including detachment from the
primary tumour, transmigration and attachment to the distant peritoneum, invasion
into subperitoneal tissue and proliferation with blood vascular neogenesis. In
the present review, the progress of each step is discussed. Milky spots, as a
lymphatic apparatus, are indicative of lymphatic orifices on the surface of the
peritoneum. These stomata are open gates for peritoneal-free cancer cells to
migrate into the submesothelial space. Therefore, milky spots provide suitable
'soil' for cancer cells to implant. Other theories have also been proposed to
clarify the peritoneal dissemination process, including the transvessel
metastasis theory, which suggests that the peritoneal metastasis of gastric
cancer develops via a vascular network mediated by hypoxia inducible factor
1alpha.
PMID- 29344128
TI - Three-dimensional cell culture: A powerful tool in tumor research and drug
discovery.
AB - In previous years, three-dimensional (3D) cell culture technology has become a
focus of research in tumor cell biology, using a variety of methods and materials
to mimic the in vivo microenvironment of cultured tumor cells ex vivo. These 3D
tumor cells have demonstrated numerous different characteristics compared with
traditional two-dimensional (2D) culture. 3D cell culture provides a useful
platform for further identifying the biological characteristics of tumor cells,
particularly in the drug sensitivity area of the key points of translational
medicine. It promises to be a bridge between traditional 2D culture and animal
experiments, and is of great importance for further research in the field of
tumor biology. In the present review, previous 3D cell culture applications,
focusing on anti-tumor drug susceptibility testing, are summarized.
PMID- 29344129
TI - Update on radionuclide therapy in oncology.
AB - Unstable isotopes and their capacity to emit ionizing radiation have been
employed in clinical practice not only for diagnostic, but also for therapeutic
purposes, with significant contribution in several fields of medicine and
primarily in the management of oncologic patients. Their efficacy is associated
with their ability to provide the targeted delivery of ionizing radiation for a
determined duration. These compounds can be used for curative or palliative
treatment, as well as for a diagnostic-therapeutic (theranostic) approach. This
review summarises the most recent trends in radionuclide treatment for several
malignancies, including prostate cancer, neuroendocrine tumours, and
hematological and thyroid malignancies, in which radionuclide-based therapies
have been employed with high effectiveness.
PMID- 29344130
TI - Potential functions and implications of circular RNA in gastrointestinal cancer.
AB - Circular RNAs (circRNAs) are a novel type of endogenous non-coding RNA that have
gained attention from researchers for their involvement in multiple biological
processes. circRNAs are ubiquitously expressed in eukaryotic cells and regulate
gene expression at the transcriptional or post-transcriptional level by
interacting with microRNAs (miRNAs) or other molecules. The present review
provides an overview of circRNAs, as well as insights into their roles in the
development and progression of gastrointestinal cancer. Furthermore, combined
with reported data, the present review investigates the potential of circRNAs to
become diagnostic or predictive biomarkers of gastrointestinal cancer and may
provide novel insights into the treatment of associated cancer types.
PMID- 29344131
TI - A novel variant translocation (1;9)(p22;q34) resulting in a DEK/NUP214 fusion
gene in a patient with acute myeloid leukemia: A case report.
AB - The present case report describes a 46-year-old female patient diagnosed with M4
acute myeloid leukemia (AML), accompanied with a t(1;9)(p22;q34) chromosomal
abnormality. Transcriptome sequencing identified a DEK proto-oncogene
(DEK)/nucleoporin (NUP)214 fusion gene, which results from the t(6;9)(p23;q34)
chromosomal translocation. Polymerase chain reaction analysis and fluorescence in
situ hybridization were used to verify the existence of the DEK/NUP214 fusion
gene. Few patients with AML with the t(6;9)(p23;q34) chromosomal translocation
have been reported to have other chromosomal or karyotype changes. To our
knowledge, no AML patient with the DEK/NUP214fusion gene but without the classic
t(6;9)(p23;q34) translocations had been reported until now. The prognosis of AML
cases with the DEK/NUP214 fusion gene is poor. The rate of complete remission is
~65% (71% in children, 58% in adult patients), while the estimated 5-year
survival rate is 28% for children and 9% for adults. The 2008 revision of World
Health Organization classification have defined the DEK/NUP214 mutation as a
recurrent genetic abnormality of AML. The overall survival of the patient in the
current report was ~29 months, and they relapsed twice. To the best of our
knowledge, this is the first report of at(1;9)(p22;q34) variant translocation
that results in expression of the DEK/NUP214 fusion gene.
PMID- 29344132
TI - Aberrant NLRP3 inflammasome associated with aryl hydrocarbon receptor potentially
contributes to the imbalance of T-helper cells in patients with acute myeloid
leukemia.
AB - Acute myeloid leukemia (AML) is a hematological malignancy in which the immune
response serves a pivotal role in progression. Aryl hydrocarbon receptor (AHR) is
involved in the modulation of the immune system, particularly in the
differentiation of T-helper cell (Th) subsets. Although the NLR family pyrin
domain-containing 3 (NLRP3) inflammasome has been implicated as essential in the
pathogenesis of autoimmune and inflammatory diseases, the role it serves in the
development of AML remains unknown. Therefore, in order to identify and describe
the possible roles of AHR, as well as NLRP3 inflammasome, in the pathogenesis of
AML and their relationship with Th subsets (Th1 Th22), the present study
investigated the mRNA expression levels of AHR and NLRP3 inflammasome molecules
in the peripheral blood and bone marrow. Concentrations of plasma IL-18 were also
investigated in peripheral blood by ELISA, as well as the proportions of Th22 and
Th1. In the present study, there were three groups: Newly diagnosed (ND)
patients; complete remission (CR); and normal controls. A markedly increased
expression of NLRP3 inflammasome molecules in bone marrow mononuclear cells
(BMMCs) from newly diagnosed (ND) patients compared with patients in complete
remission (CR) was identified. NLRP3 inflammasome molecules were also observed to
be aberrantly expressed in peripheral blood (PB) mononuclear cells (PBMCs),
accompanied with aberrant interleukin (IL)-18 levels in PB plasma. The relative
level of IL-18 mRNA became normal after the ND patients with AML achieved CR. In
bone marrow, the expression of AHR was significantly higher in ND patients than
in CR patients. Furthermore, the expression level of NLRP3 inflammasome molecules
was significantly correlated with AHR expression in patients with AML. In the Th
subsets, a significantly increased proportion of Th22 in PB from ND patients
compared with CR patients or controls was identified, accompanied with decreased
Th1. It was concluded that the NLRP3 inflammasome, associated with AHR, was
involved in the development of AML and may have influenced the differentiation of
Th subsets.
PMID- 29344133
TI - Improved treatment of early small hepatocellular carcinoma using sorafenib in
combination with radiofrequency ablation.
AB - Small hepatocellular carcinoma is an important leading cause of death amongst
cancer patients, our study was designed in order to test the hypothesis that
radiofrequency ablation (RFA) combined with a chemotherapeutic drug would improve
the outcome for patients. Two groups of patients presenting early small
hepatocellular carcinoma were treated with either conventional RFA alone (50
individuals in the control group), or with a combination of RFA and oral
sorafenib (40 individuals in an observation group). Individual clinical and
laboratory evaluations were done during an average follow-up time of 35 months,
and all the data recorded was used to compare results of both treatment
approaches. Tumor-free survival, relapse rate and survival rate, RFA interval and
number of treatments, overall efficacy and the incidence of complications were
analyzed. Serum levels of vascular endothelial growth factor (VEGF), connective
tissue growth factor (CTGF), hypoxia inducible factor-1alpha (HIF-1alpha) and
osteopontin (OPN) were measured and compared. Our results show that the patients
in the treatment group had statistically significant prolonged tumor-free
survival, decreased relapse and increased survival rates. Also, the patients in
the treatment group had significantly more prolonged average intervals of RFA and
a lower number of treatments. Furthermore, the overall efficacy in the treatment
group was increased, yet the incidence of complications was similar between both
groups. Moreover, the serum levels of known tumorigenic factors VEGF, CTGF, HIF
1alpha and OPN, which were similar between both groups before treatment, improved
more markedly after the treatment in the observation group patients. Based on
these findings, we propose that sorafenib in combination with percutaneous RFA is
safe and efficacious, and a superior treatment for early small hepatocellular
carcinoma. Larger studies are needed to corroborate our results.
PMID- 29344134
TI - A novel classification system for the evaluation and reconstruction of oral
defects following oncological surgery.
AB - Accurate evaluation of oral tissue defects following oncological surgery is
necessary for the subsequent reconstruction. However, there is currently no
effective classification system for oral defects in the clinical setting. The
present study therefore developed a clinical classification system for the
evaluation and reconstruction of oral defects. A retrospective cohort study was
performed. A two-dimensional classification system based on coronal computed
tomography/magnetic resonance imaging was developed and validated by 145 cases
with oral defects. Oral defects could be classified into 6 types (I-VI)
horizontally and 2 classes (a and b) vertically. The proportion of the various
types was as follows: Type I, 35.9%; type II, 21.4%; type III, 23.4%; type IV,
4.8%; type V, 2.1%; and type VI, 12.4%. Among them, 91 cases (62.8%) were class a
and 54 cases (37.2%) were class b. Type Ia-Va represented the unilateral 1-5
subsites involving superficial oral defects without mandibular continuity
destruction (88 cases, 60.7%). Type Ib-Vb (+M) represented the unilateral 1-5
subsites involving deep oral defects with segmental mandibular continuity
destruction (38 cases, 26.2%). Type I-V (+S) represented the unilateral through
and through oral defects with cheek skin involvement (10 cases, 6.9%). Type VI
represented bilateral oral defects (18 cases, 12.4%). The present classification
system for the evaluation of the oral defects was simple and practical, and could
identify the common types of oral defects and guide the reconstruction.
PMID- 29344135
TI - Identification of differentially expressed genes in oral squamous cell carcinoma
TCA8113 cells.
AB - Previous studies have demonstrated that cancer cells with increased levels of
aldehyde dehydrogenase 'bright' activity (ALDHbr) exhibit stem cell properties
compared with cells exhibiting decreased ALDH activity (ALDHlow). To screen
possible biomarkers of cancer stem cells in tongue squamous cell carcinoma,
ALDHbr and ALDHlow cells were isolated from the tongue squamous cell carcinoma
TCA8113 cell line, and suppression subtractive hybridization was performed to
identify differentially expressed genes in the two subpopulations. A total of 240
positive clones were randomly selected for sequencing and were functionally
characterized using bioinformatical tools. The results of the present study
identified the differential expression of 104 clones, 62 of which corresponded to
known genes and 42 of which corresponded to unknown genes. Cluster analysis
revealed that the known genes were involved in the regulation of the cell cycle
and cell differentiation. In addition, analysis of 10 signaling pathways revealed
that genes were markedly altered in the ALDHbr cell subpopulation. Additional
study is required to identify the function that these genes serve in the
biomolecular regulatory mechanisms of cancer stem cells and to assist in
explaining the biological behavior of oral squamous cell carcinoma.
PMID- 29344136
TI - Clinical outcome of extended-field irradiation vs. pelvic irradiation using
intensity-modulated radiotherapy for cervical cancer.
AB - The aim of the present study was to evaluate the distinctions in survival and
toxicity between patients with cervical cancer with common iliac node or para
aortic node involvement, who were treated with extended-field intensity-modulated
radiotherapy (EF-IMRT) and patients with or without lower involved pelvic nodes,
who were treated with pelvic IMRT. A total of 55 patients treated with EF-IMRT
and 52 patients treated with pelvic IMRT at the Sun Yat-Sen University Cancer
Center (Guangzhou, China) were retrospectively analyzed. Patients treated with EF
IMRT had the highest level of lymph node involvement to the para-aortic or common
iliac nodes, while patients treated with pelvic IMRT had no para-aortic or common
iliac nodes involved (P<0.001). The median follow-up time was 29.5 months. The 3
year overall survival (OS) rates of EF-IMRT and pelvic IMRT were 79.4 and 82.3%
(P=0.45), respectively, and the 3-year disease-free survival (DFS) rates of EF
IMRT and pelvic IMRT were 61.0 and 73.7% (P=0.55), respectively. Cox's regression
analysis revealed that EF irradiation was a protective prognostic factor for OS
and DFS. A total of 16 patients in the EF-IMRT group and 13 patients in the
pelvic IMRT group experienced treatment failure (P=0.67), with the patterns of
failure being the same for the two groups (P=0.88). The cumulative incidence of
grade 3 and 4 acute toxicities in the EF-IMRT group was 34.5%, in comparison with
19.2% in the pelvic group (P=0.048). The results of the present study suggest
that patients with cervical cancer with grossly involved common iliac or para
aortic nodes should be electively subjected to EF irradiation to improve the
survival and alter patterns of recurrence. Notably, EF irradiation delivered via
IMRT exhibits an increased toxicity incidence, however, this remains within an
acceptable range.
PMID- 29344137
TI - The association between aquaporin-1 expression, microvessel density and the
clinicopathological features of hepatocellular carcinoma.
AB - The present study aimed to evaluate the effects of aquaporin-1 (AQP1) level and
intratumoral microvessel density (IMD) on the clinicopathological features of
patients with hepatocellular carcinoma (HCC). The AQP1 expression levels, IMD and
AQP1/IMD ratios in patients with HCC were measured using a semi-quantitative
immunohistochemical technique. The association between these features and
clinicopathological variables were evaluated. The prognostic impact of AQP1 and
IMD on overall survival (OS), and 5-year disease-free survival (DFS) of HCC
patients was investigated retrospectively. P<0.05 was considered to indicate a
statistically significant difference. A total of 90 cases of HCC were included in
the present study. AQP1 was markedly expressed in the membranes of microvessels
and small vessels, but seldom in hepatocellular carcinoma cells. Blood vessels in
the tumors were markedly stained by anti-cluster of differentiation 34 antibody.
AQP1 expression and IMD was significantly correlated with tumor size, histologic
grade, Child-Pugh classification, microvascular invasion and tumor-node
metastasis (TNM) stage (P<0.05). Concurrently, for the 5-year DFS and OS, a
larger tumor size, poorly differentiated histological grade, B and C Child-Pugh
classification, presence of microvascular invasion, high TNM stage, a high AQP1
expression and a high IMD were significant risk factors for mortality.
Multivariate analysis revealed that TNM stage and IMD were independent
unfavorable prognostic markers for 5-year DFS (P=0.049 and P=0.025, respectively)
and OS (P=0.043 and P=0.042, respectively). These data suggest that high AQP1
expression and IMD are associated with tumor progression and prognosis in HCC.
The IMD level may serve as an independent indicator for the 5-year DFS and OS.
PMID- 29344138
TI - Clinical and genetic analysis of tuberous sclerosis complex-associated renal
angiomyolipoma in Chinese pedigrees.
AB - Tuberous sclerosis complex-associated renal angiomyolipoma (TSC-RAML) confers a
high risk of bleeding and even mortality. However, data on TSC-RAML in Chinese
pedigrees is extremely lacking. The present study aimed to investigate its
clinical and genetic characteristics by obtaining a detailed medical history from
6 probands and their family members, and reassessing blood tests, computed
tomography and renal dynamic imaging examinations that were conducted in the TSC
RAML patients. The TSC1/TSC2 mutation was detected in 2 families. A total of 3
TSC-RAML patients underwent partial nephrectomy due to a high bleeding risk, and
the other 2 were treated with everolimus. The remaining 6 TSC-RAML patients
received no clinical intervention and only had clinical follow-uzp. It was found
that nearly 37% (18/49) were TSC patients, with the mean +/- standard deviation
diagnostic age being 34.22+/-17.73 years old in the 6 pedigrees, 61% (11/18) of
whom suffered from TSC-RAML. In the 11 TSC-RAML patients, the maximum diameter of
the tumor ranged between 1.20 and 32.50 cm (mean +/- standard deviation, 11.48+/
8.40 cm), the unilateral glomerular filtration rate ranged between 27.20 and
60.10 ml/min (mean +/- standard deviation, 42.55+/-9.73 ml/min), the serum
creatinine level ranged between 40.00 and 90.00 umol/l (mean +/- standard
deviation, 64.84+/-16.15 umol/l) and the hemoglobin concentration ranged between
76.00 and 140.00 g/l (mean +/- standard deviation, 107.73+/-21.04 g/l).
Pathogenic mutations of TSC1 (c.733C>T) and TSC2 (c.788_789insC) were detected in
family B and C, respectively, as well as certain non-pathogenic mutations, with
the maximum diameter of TSC-RAML being 0 cm and 10.3 cm in the two patients from
family B and 16 cm and 1.2 cm in the two patients from family C. Expression of
phosphorylated-mechanistic target of rapamycin was determined in the TSC-RAML
tissues by immunohistochemistry. The maximum diameter of the tumor decreased by
4.90 and 5.30 cm, respectively, in the 2 patients treated with everolimus after 3
months. In conclusion, TSC cannot be easily diagnosed due to its variable
characteristics. Growth of TSC-RAML may increase the bleeding risk and reduce the
level of hemoglobin, but it does not greatly affect renal function. Individual
differences in tumor dimensions existed even with the same pathogenic mutation,
except for cases of coexistent non-pathogenic mutations. Everolimus treatment
appears to be able to significantly reduce the size of TSC-RAML.
PMID- 29344139
TI - NLS-RARalpha is a novel transcriptional factor.
AB - Acute promyelocytic leukemia (APL) is characterized by the presence of the
promyelocytic leukemia (PML)-retinoic acid receptor-alpha (RAR-alpha) fusion
protein. PML-RARalpha can be cleaved by neutrophil elastase (NE) in several
positions in cells in the promyelocytic stage, nuclear location signal (NLS)
negative PML and NLS-RARalpha may be the products of PML-RARalpha by NE. The
function of NLS-RARalpha may be affected by the addition of NLS, which would
alter its localization in cells, as the role of NLS is to identify proteins for
transport to the nucleus. Preliminary experiments demonstrated that the
overexpression of NLS-RARalpha in HL-60 cells could promote cellular
proliferation and inhibit cellular differentiation. Following treatment with all
trans retinoic acid (ATRA), the degree of cellular differentiation was enhanced.
In the present study, the localization of NLS-RARalpha was identified and its
activity as a novel transcriptional factor was assessed, which may be critical in
the development of APL. The location of NLS-RARalpha was detected in the nucleus
and cytoplasm by indirect immunofluorescence and western blot analysis, with
expression in the nucleus revealed to be increased compared with that in the
cytoplasm. Next, native-PAGE was performed and NLS-RARalpha and RXRalpha were
revealed to form heterodimers in the nucleus. In addition, co-immunoprecipitation
revealed an interaction between NLS-RARalpha and retinoid X receptor-alpha
(RXRalpha). An electrophoresis mobility shift assay (EMSA) indicated that NLS
RARalpha could bind retinoic acid response elements (RAREs) in the presence of
ATRA. Indeed, NLS-RARalpha could bind RAREs just as WTRARalpha could, including
the RAREs direct repeat-2 (DR-2) and DR-5. In addition, results from a luciferase
reporter gene assay demonstrated that NLS-RARalpha could mediate the activity of
RAREs that it bound. Together, these results indicated that NLS-RARalpha may be a
novel transcription factor that contributes to leukemogenesis by competitively
binding RAREs as heterodimers with RXRalpha, just as PML-RARalpha does, thus
repressing the gene transcription essential for myeloid differentiation. These
findings indicate the potential role of NLS-RARalpha targeted therapy in APL.
PMID- 29344140
TI - Familial genetic tuberous sclerosis complex associated with bilateral giant renal
angiomyolipoma: A case report.
AB - Tuberous sclerosis complex (TSC) is an autosomal dominant disease involving
multiple organs, but there are a limited number of reports on family TSC. In the
present report, a case of a 52-year-old female with a familial genetic TSC,
associated with bilateral giant renal angiomyolipoma, was described. The mother,
second elder brother and daughter of the patient all exhibited TSC, but the
clinical manifestations, and therapeutic prognosis between the family members
were not the same. The present case report aimed at identifying an effective
diagnostic method and treatment through additional study of familial genetic TSC,
in order to prolong and improve the quality of life for patients with TSC.
According to the present case and relevant literature reviews, it is suggested
that fetal gene detection during pregnancy could prevent the passing of this
disease onto further generations. Furthermore, early application of drug
treatment may control the development of the disease in diagnosed patients. The
combination of classical treatments with a small dose of mammalian target of
rapamycin inhibitors is the typical recommendation, which may control the
development of the disease more effectively and decrease adverse side-effects.
PMID- 29344141
TI - The expression of S100B protein in serum of patients with brain metastases from
small-cell lung cancer and its clinical significance.
AB - The objective of the present study was to investigate the expression of S100B
protein in serum of patients with brain metastases from small cell lung cancer
(SCLC), and its clinical significance. A total of 138 patients with SCLC were
selected from June 2013 to December 2015. Simultaneously, 138 healthy adult
volunteers (healthy controls) were selected in the medical examination center of
People's Hospital of Rizhao. Among the 138 patients with SCLC, 48 had liver
metastases and 44 had brain metastases. Of the remaining 46 patients, 20 were
initially diagnosed with SCLC and 26 underwent surgery and postoperative
chemotherapy. The levels of serum S100B in patients and healthy controls were
measured by ELISA, and analyzed by SPSS 20.0 statistical software. The serum
S100B protein levels in patients with SCLC were significantly higher than those
in healthy controls (p<0.05). Among the subgroups of patients with SCLC, the
levels of serum S100B in patients with brain metastases were significantly higher
than in the other subgroups (p<0.05). No significant differences were found
between the other subgroups, except for the brain metastases group. We found that
serum S100B protein expression levels were significantly reduced in patients with
brain metastases after cobalt-60 radiotherapy (p<0.05). During follow-up, we
found that higher expression of S100B protein was usually associated with poorer
prognosis, higher mortality rate at 1 year, and lower survival rate. In
conclusion, S100B protein can serve as a serological marker for brain metastases
from SCLC, which provides important theoretical support for early detection of
brain metastases.
PMID- 29344142
TI - Isolation and identification of tumor-initiating cell properties in human
gallbladder cancer cell lines using the marker cluster of differentiation 133.
AB - The present study aimed to isolate and identify the properties of the cluster of
differentiation (CD)133+ subset in human gallbladder cancer cells. The CD133+ and
CD133- subpopulations of the GBC-SD cell line were separated using immunomagnetic
separation, and the biological features of the two subpopulations were analyzed
in vitro and in vivo. In particular, the present study aimed to determine whether
the two subpopulations were resistant to anti-tumor reagents and to identify the
underlying molecular mechanisms involved. Following cell sorting of GBC-SD cells
using immunomagnetic beads, 90.2+/-2% of cells were identified as CD133+.
Immunofluorescence confirmed that CD133 was expressed at higher levels in the
Cd133+ group compared with the CD133- group. The proliferation of the CD133+
group was significantly increased compared with the CD133- group in vitro and in
vivo. Following treatment with fluorouracil or gemcitabine, cells in the CD133+
group exhibited a decreased sensitivity to these drugs. The number of
transmembrane cells was significantly increased in the CD133+ group compared with
the CD133- group. In addition, the expression levels of ATP binding cassette
subfamily G member 2, CD44, C-X-C motif chemokine receptor 4 (CXCR4),
phosphorylated-protein kinase B (Akt) and CD133 in the CD133+ group were
significantly increased, compared with those in the CD133- group. In CD133+ GBC
SD cells, stromal cell-derived factor 1alpha (SDF-1alpha) or treatment with
AMD3100, an inhibitor of CXCR4, promotes or suppresses the SDF-1alpha/CXCR4 axis,
respectively, resulting in increased or decreased CD133 expression through the
Akt signaling pathway. Inhibition of the Akt signaling pathway resulted in
decreased CD133 expression in GBC-SD cells. Immunomagnetic beads were
successfully used for isolation of the CD133+ subset from GBC-SD cells.
Furthermore, the CD133+ subset revealed an increased potential for tumor
formation, cell proliferation, invasion and resistance to chemotherapeutic agents
with expression of stem cell-associated genes. Therefore, in GBC-SD cells, the
CXCR4/Akt/CD133 signaling pathways may be activated.
PMID- 29344143
TI - Function of cell-cycle regulators in predicting silent pituitary adenoma
progression following surgical resection.
AB - The present study investigated the use of cell-cycle regulators for predicting
the progression of silent pituitary adenoma (SPA) following surgical resection,
via immunohistochemical analysis of tumor samples obtained by surgical resection.
The medical records of patients diagnosed with SPA between January 2000 and
December 2013 in the Samsung Changwon Hospital, Sungkyunkwan University School of
Medicine (Changwon, South Korea) were reviewed. Immunohistochemical staining was
performed on sections of the archived, paraffin-embedded tissues obtained by
surgery, with all tissues stained for cell-cycle regulatory proteins p16, p15,
p21, cyclin-dependent kinase (CDK)4, CDK6, retinoblastoma protein (pRb) and
cyclin D1, as well as E3 ubiquitin-protein ligase mib1 (MIB-1) antigen and p53.
The primary end-point was to investigate the expression of cell-cycle regulatory
proteins in SPA. The secondary end-point was to estimate the progression-free
survival of patients with SPA following surgical resection and to identify its
association with the expression of cell-cycle regulatory proteins. Of the 127 SPA
samples, 44 (34.6%) were from patients with progression during a mean follow-up
period of 62.4 months (range, 24.2-118.9 months). Immunohistochemical
overexpression was identified in 61 samples (48.0%) for p16, 38 samples (29.9%)
for p15, 19 samples (15.0%) for p21, 49 samples (38.6%) for CDK4, 17 samples
(13.4%) for CDK6, 57 samples (44.9%) for pRb and in 65 samples (51.2%) for cyclin
D1. Multivariate analysis revealed that null cell adenoma [95% confidence
interval (CI), 0.276-0.808], somatotroph SPAs (95% CI, 1.296-3.121), corticotroph
SPAs (95% CI, 1.811-4.078), pluripotent SPAs (95% CI, 2.264-5.194), decreased
expression of p16 (95% CI, 2.724-5.588), overexpression of pRb (95% CI, 2.557
5.333), cyclin D1 (95% CI, 1.894-4.122) and MIB-1 (95% CI, 1.561-4.133),
increased mitotic index (95% CI, 1.228-4.079), increased p53 expression (95% CI,
1.307-4.065) and invasion into the cavernous sinus (95% CI, 3.842-7.502)
predicted SPA progression following resection. The results of the present study
suggested that specific cell-cycle regulators, including p16, cyclin D1 and pRb,
were associated with SPA progression.
PMID- 29344144
TI - Melanoma differentiation-associated gene-7 suppresses human gastric cancer cell
invasion and migration.
AB - Gastric cancer is one of the most common types of cancer in the world. Patients
with gastric cancer often respond poorly to conventional chemotherapies,
therefore more comprehensive therapy is required. Melanoma differentiation
associated gene-7 (MDA-7), also termed interleukin-24, is a potent tumor
suppressor gene. Numerous studies have demonstrated that MDA-7 suppresses the
growth and induces the apoptosis of cancer cells. In the present study, the MDA-7
gene was transfected into human gastric cancer AGS cells using adenovirus.
Transwell and wound healing assays were performed to evaluate AGS cell invasion
and migration, respectively. Western blotting was used to detect the expression
of epithelial (E)-cadherin, cluster of differentiation (CD)44 and matrix
metalloproteinase (MMP)-2 and MMP-9 proteins. A recombinant virus package was
successfully constructed, and it was verified using western blotting that
exogenous MDA-7 was highly expressed in the AGS cells. MDA-7 overexpression
inhibited invasion and migration, decreased CD44, MMP-2 and MMP-9 expression, and
increased epithelial (E-)cadherin expression in the AGS cells. Results of the
present study revealed that MDA-7 inhibits gastric cancer invasion and metastasis
by inhibiting CD44, MMP-2 and MMP-9 expression and by promoting E-cadherin
expression.
PMID- 29344145
TI - MicroRNA-320 inhibits cell proliferation and invasion in breast cancer cells by
targeting SOX4.
AB - Dysregulation of microRNAs (miRs) can contribute to cancer development and
progression. In the present study, the function and underlying molecular
mechanisms of miR-320 in breast cancer tumorigenesis and progression were
investigated. The results of a reverse transcription-quantitative polymerase
chain reaction analysis demonstrated that miR-320 was frequently downregulated in
breast cancer tissues compared with adjacent normal tissues. In addition,
knockdown of miR-320 in breast cancer cell lines promoted cell proliferation and
invasion in vitro, whereas miR-320 overexpression had the opposite effect.
Furthermore, a Dual-Luciferase reporter assay indicated that SRY-box 4 (SOX4) is
a direct target of miR-320, and the restoration of SOX4 in miR-320-overexpressing
cells attenuated the tumor-suppressive effects of miR-320. Collectively, these
results indicated that miR-320 acts as a tumor suppressor in breast cancer
tumorigenesis and progression.
PMID- 29344146
TI - Integrated microRNA-mRNA analyses of distinct expression profiles in follicular
thyroid tumors.
AB - MicroRNAs (miRNAs/miRs) are small non-coding RNAs identified in plants, animals
and certain viruses; they function in RNA silencing and post-transcriptional
regulation of gene expression. miRNAs also serve an important role in the
pathogenesis, diagnosis and treatment of tumors. However, few studies have
investigated the role of miRNAs in thyroid tumors. In the present study, the
expression of miRNA and mRNA was compared between follicular thyroid carcinoma
(FTC) and follicular thyroid adenoma (FA) samples, and then miRNA-mRNA regulatory
network analysis was performed. Microarray datasets (GSE29315 and GSE62054) were
downloaded from the Gene Expression Omnibus, and profiling data were processed
with R software. Differentially expressed miRNAs (DEMs) and differentially
expressed genes (DEGs) were determined, and Gene Ontology enrichment analysis was
subsequently performed for DEGs using the Database for Annotation, Visualization
and Integrated Discovery. The target genes of the DEMs were identified with
miRWalk, miRecords and TarMir databases. Network analysis of the DEMs and DEMs
targeted DEGs was performed using Cytoscape software. In GSE62054, 23
downregulated and 9 upregulated miRNAs were identified. In GSE29315, 42
downregulated and 44 upregulated mRNAs were identified. A total of 36 miRNA-gene
pairs were also identified. Network analysis indicated a co-regulatory
association between miR-296-5p, miR-10a, miR-139-5p, miR-452, miR-493, miR-7, miR
137, miR-144, miR-145 and corresponding targeted mRNAs, including TNF receptor
superfamily member 11b, benzodiazepine receptor (peripheral) -associated protein
1, and transforming growth factor beta receptor 2. These results suggest that
miRNA-mRNAs networks serve an important role in the pathogenesis, diagnosis and
treatment of FTC and FA.
PMID- 29344147
TI - Systematic analysis of the molecular mechanism of microRNA-124 in hepatoblastoma
cells.
AB - The present study aimed to identify the molecular mechanisms of microRNA-124
(miRNA-124/miR-124) in hepatoblastoma. The GSE6207 microarray dataset, obtained
from the Gene Expression Omnibus database, included samples extracted from HepG2
cells transfected with miR-124 duplex (the experimental group) or negative
control (the control group) at 4, 8, 16, 24, 32, 72 and 120 h after transfection.
Differentially expressed genes (DEGs) were screened between the two groups. miR
124 activity was inferred based on the expression of its target genes. The mRNAs
targeted by miR-124 were predicted and a miR-124-target mRNA network was
constructed. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes
pathway enrichment analyses were performed for the target genes. The number of
DEGs was highest at 72 h. The experimental group had higher miR-124 activity than
that of the control group at 4, 8, 16, 24 and 120 h. Small GTPase-mediated signal
transduction and Ras protein signal transduction were significant GO terms
enriched with syndecan binding protein (SDCBP), Ras homolog family member G
(RHOG) and Rho-GDP dissociation inhibitor-alpha (ARHGDIA). Regulation of actin
cytoskeleton, D-glutamine and D-glutamate metabolism, and axon guidance were
significant pathways. Axon guidance pathway was associated with neuropilin
(NRP1), MET proto-oncogene, receptor tyrosine kinase (MET) and semaphorin 7A, GPI
membrane anchor (SEMA7A). Small GTPase-mediated signal transduction, Ras protein
signal transduction, regulation of actin cytoskeleton pathway, D-glutamine and D
glutamate metabolism pathway, axon guidance pathway, SDCBP, RHOG, ARHGDIA, NRP1,
SEMA7A, and MET may be implicated in the underlying mechanisms of miR-124
overexpression in hepatoblastoma.
PMID- 29344148
TI - Identification of potentially critical differentially methylated genes in
nasopharyngeal carcinoma: A comprehensive analysis of methylation profiling and
gene expression profiling.
AB - The present study aimed to identify potentially critical differentially
methylated genes associated with the progression of nasopharyngeal carcinoma
(NPC). Methylation profiling data of GSE62336 deposited in the Gene Expression
Omnibus database were used to identify differentially methylated regions (DMRs)
and differentially methylated CpG islands (DMIs). Concurrently, differentially
expressed genes (DEGs) were identified using a meta-analysis of three gene
expression datasets (GSE53819, GSE13597 and GSE12452). Subsequently, methylated
DEGs were identified by comparing DMRs and DEGs. Furthermore, functional
associations of these methylated DEGs were analyzed via constructing a functional
network using GeneMANIA prediction server. In total, 1,676 hypermethylated genes,
28 hypomethylated genes, 17 DMIs and 2,983 DEGs (1,655 upregulated and 1,328
downregulated) were identified. Among these DEGs, 135 downregulated genes were
hypermethylated; of these, dual specificity phosphatase 6 (DUSP6) and tenascin XB
(TNXB) contained DMIs. In the functional network, 154 genes and 1,651 association
pairs were included. DUSP6 was predicted to exhibit genetic interactions with
other hypermethylated DEGs such as malic enzyme 3 and ST3 beta-galactoside alpha
2,3-sialyltransferase 5; TNXB was predicted to be co-expressed with a set of
hypermethylated DEGs, including EPH receptor B6, aldehyde dehydrogenase 1 family,
member L1 and glutathione peroxidase 3. The hypermethylated DEGs may be involved
in the progression of NPC, and they may become novel therapeutic targets for NPC.
PMID- 29344149
TI - Hepatoma-derived growth factor functions as an unfavorable prognostic marker of
human gliomas.
AB - Hepatoma-derived growth factor (HDGF) regulates various cellular processes
involved in the onset and development of tumors. To evaluate the role of HDGF in
human gliomas, western blotting analysis, immunohistochemistry staining and
reverse transcription-quantitative polymerase chain reaction were performed to
detect HDGF protein and mRNA expression levels in glioma and intractable
epileptic brain tissue. Various clinicopathological characteristics, including
age, gender, World health Organization grade, HDGF expression level, Karnofsky
performance Status (KPS) and Ki-67 index were obtained from medical records. The
correlation between HDGF expression and these clinicopathological characteristics
was statistically evaluated. Following this, multivariate liner regression was
used to evaluate their effect on patient survival time. HDGF expression, at the
protein and mRNA levels, was observed to be more upregulated in glioma tissues
compared with intractable epileptic brain tissue without tumor. Furthermore, the
level of HDGF expression was positively associated with the grade of malignancy
[grades II~IV, Ki-67 index >=20% or KPS <80 (P<0.05)] and poor prognosis in
glioma patients. Notably, the univariate survival analysis identified a negative
correlation between HDGF-expression and survival time (P<0.01) and multivariate
liner regression demonstrated that HDGF expression is an independent prognostic
factor for gliomas (P=0.01). Overall, HDGF upregulation may be a crucial step in
the development and invasion of glioma. Further survival analysis highlighted its
prognostic value for this malignancy, implying its potential as a promising
therapeutic target for gliomas.
PMID- 29344150
TI - Expression of CD24 and B7-H3 in breast cancer and the clinical significance.
AB - This study aimed to investigate the correlation between the expression of CD24
and B7-H3 in breast cancer tissues and the clinical significance. Expression of
CD24 and B7-H3 in breast cancer and adjacent tissues were detected by
immunohistochemistry. Quantitative PCR was used to detect the expression of CD24
and B7-H3 mRNA in breast cancer and adjacent tissues. The expression of CD24 and
B7-H3 protein in breast cancer and adjacent tissues was detected by
immunoblotting. The correlation between the expression levels of the two proteins
was analyzed and the relationship between the expression of two proteins and the
5-year survival of breast cancer patients was investigated. CD24 and B7-H3 were
positively expressed in breast cancer and adjacent tissues, the CD24-positive
rate was 75.7 and 25.7%, respectively, and the B7-H3-positive rate was 56.8 and
43.2%, respectively, and the differences were statistically significant (P<0.05).
The expression of CD24 was positively correlated with the expression of B7-H3
(Spearman's correlation coefficient r, 0.297; p=0.036). The positive and negative
expression of CD24 and B7-H3 significantly affected the 5-year survival of breast
cancer patients (P<0.05). Quantitative PCR results showed that the expression
levels of CD24 and B7-H3 mRNA in breast cancer tissues were significantly higher
than those in adjacent tissues (P<0.05). The expression levels of CD24 and B7-H3
protein in breast cancer tissues were also significantly higher than those in
adjacent tissues (P<0.05). CD24 and B7-H3 were highly expressed in breast cancer,
suggesting that both CD24 and B7-H3 were related to the development of breast
cancer. Five-year survival analysis of breast cancer patients showed that the
high expression of CD24 and B7-H3 were correlated with the poor prognosis of
patients. Thus, CD24 and B7-H3 may become new targets for the treatment of breast
cancer.
PMID- 29344151
TI - Expression of EZH2 in endometrial carcinoma and its effects on proliferation and
invasion of endometrial carcinoma cells.
AB - Expression of enhancer of zeste homolog 2 (EZH2) has been implicated in cancer
pathology, but research on its mechanistic activity is limited. The present study
sought to assess the levels expression of EZH2 in patients with endometrial
carcinoma (EC) and to explore the effects of EZH2 downregulation on the
biological behavior of endometrial carcinoma RL-952 cells. Samples were obtained
from a total of 104 patients with EC and an immunohistochemical assay was used to
detect the expression of EZH2 in cancer and adjacent tissues. The relationship
between the expression of EZH2 and the clinicopathological features was analyzed.
Endometrial carcinoma RL-952 cells were transfected with chemically synthesized
siRNA to conduct targeting inhibition of EZH2 expression. The expression levels
of EZH2 protein were detected by immunoblotting. MTT and Transwell assays were
used to detect the changes of cell proliferation and invasion after EZH2
downregulation. Of the 104 cases of endometrial carcinoma samples, 71 cases
showed positive expression of EZH2, with an expression rate of 68.27%. In 104
cases of adjacent tissue samples, 25 cases showed positive expression of EZH2,
with an expression rate of 24.03%. The expression of EZH2 in endometrial
carcinoma tissue was significantly higher than that in adjacent tissue (P<0.05).
The expression of EZH2 in endometrial carcinoma tissue was not correlated with
the menopausal status and age of patients (P>0.05), but was correlated with the
histological grade, depth of tumor invasion, lymph node metastasis and TNM stage
(P<0.05). The expression of E2H2 was significantly downregulated by si-E2H2 and
the proliferation and invasion abilities of cells were significantly reduced
after EZH2 downregulation (P<0.05). EZH2 is closely related to the development of
endometrial carcinoma and can enhance the proliferative activity of endometrial
carcinoma RL-952 cells and promote cell invasion.
PMID- 29344152
TI - Regulation of autophagy inhibition and inflammatory response in glioma by Wnt
signaling pathway.
AB - The objective of this study was to investigate the mechanism of the function of
Wnt signaling pathway in regulating autophagy and inflammatory response in glioma
cells. Human brain glioma cells U118 were selected and divided into three groups:
i) the Wnt signaling inhibitor IWR-1 group (the observation group); ii) the PBS
negative control group (the PBS group) and iii) the blank control group. After 24
h culture, Wnt5a/beta-catenin protein, autophagy marker, microtubule-associated
proteins-1A1B-light-chain-3C (LC-3) II and Beclin I, and inflammatory factors IL
6 and TNF-alpha protein expression levels were evaluated using western blotting.
Compared with both control groups, Wnt5a/beta-catenin, IL-6 and TNF-alpha protein
expression levels were significantly lower, and LC-3II and Beclin I protein
expression levels were significantly higher in the observation group. In
conclusion, Wnt5a/beta-catenin signaling pathway regulates autophagy and
inflammatory response of glioma cells.
PMID- 29344153
TI - Efficacy and prognosis of surgery combined with 125I seed implantation in
treatment of recurrent glioma.
AB - This study evaluated the efficacy of surgery combined with 125I seed implantation
in the treatment of recurrent glioma, and analyzed prognosis-influencing factors.
A total of 66 patients with recurrent gliomas in Yidu Central Hospital of Weifang
were enrolled in the study from April, 2011 to March, 2014. Patients were
randomly divided into a control and an observation group, with 33 patients in
each group. Patients in the control group were treated with surgery alone, and
those in the observation group received surgery combined with 125I seed
implantation. Short-term curative effects in the two groups were compared using
evaluation criteria for solid tumors. The comparison included the postoperative
adverse reactions, the life quality (using the Karnofsky Performance Status or
KPS), the survival time and prognostic factors (using the Kaplan-Meier survival,
log-rank test and Cox regression analyses). Our results showed the objective
response and disease control rates in the observation group were significantly
higher than those in the control group (P<0.05). While no significant differences
in postoperative adverse reactions were found between the two groups (P>0.05).
The KPS score in the observation group was significantly higher than that in the
control group at different time points after surgery (P<0.05). The survival rate
and overall survival time of those in the observation group were significantly
higher than those of the patients in the control group (P<0.05). The univariate
analysis showed that preoperative KPS score, tumor pathological grade and degree
of tumor resection were adverse factors influencing the prognosis of the patients
(P<0.05). Also, multivariate Cox regression showed that preoperative KPS score,
tumor pathological grade, and degree of tumor resection were independent risk
factors of prognosis. Based on our findings, surgery combined with 125I seed
implantation can improve the survival rate of patients with recurrent glioma and
prolong their survival time. Tumor pathological grade, degree of tumor resection
and KPS score are the most important factors influencing the prognosis.
PMID- 29344154
TI - Study of miR-10b regulatory mechanism for epithelial-mesenchymal transition,
invasion and migration in nasopharyngeal carcinoma cells.
AB - The aim of the study was to investigate the miR-10b regulatory mechanism for
epithelial-mesenchymal transition (EMT) and its effect on the proliferation and
migration of nasopharyngeal carcinoma cells. RT-qPCR was used to detect the
expression of miR-10b in CNE1 nasopharyngeal carcinoma cell line. The NP69
nasopharyngeal mucosal cell line was used to determine the expression of miR-10b
after infection with lentivirus. The effect of miR-10b on the proliferation of
NP69 was examined using cell counting kit-8. The effect of miR-10b on NP69
migration was examined using scratch assay. Western blot analysis was used to
detect the effects of miR-10b on the expression of epithelial cell markers E
cadherin and beta-catenin and mesenchymal cell markers fibronectin, N-cadherin,
vimentin and matrix metalloproteinase-9 (MMP-9). The present study showed that
miR-10b was highly expressed in CNE1 cells. The stable expression of miR-10b
promoted the proliferation and migration of NP69 cells, downregulated the
expression of epithelial cell markers E-cadherin and beta-catenin, and
upregulated the expression of mesenchymal cell markers fibronectin, N-cadherin,
vimentin and MMP-9 resulting in cell EMT. In conclusion, miR-10b promotes the
proliferation and migration of nasopharyngeal carcinoma cells, and induces EMT in
nasopharyngeal carcinoma cells, thereby having the potential to become a new
target for the treatment of nasopharyngeal carcinoma.
PMID- 29344155
TI - CD133 mediates the TGF-beta1-induced activation of the PI3K/ERK/P70S6K signaling
pathway in gastric cancer cells.
AB - Cluster of differentiation (CD)133 has been reported to be involved in the
activation of the extracellular signal-regulated kinase (ERK) signaling pathway
in different types of cancer cells. CD133 has been reported to be involved in the
activation of the ERK signaling pathway in various cancer cells. Transforming
growth factor (TGF)-beta1 has also been reported to mediate the activation of the
ERK signaling pathway. In addition, TGF-beta1 has been previously shown to
mediate the activation of the ERK signaling pathway. Hence, the present study
investigated the function of CD133 in the TGF-beta1-induced activation of the
ERK/P70S6K signaling pathway in human gastric cancer (GC) cells. To this end, GC
cell lines SGC7901 and MKN45 were treated with TGF-beta1. The expression of
CD133, phospho-ERK (p-ERK) and phospho-P70S6 kinase (p-P70S6K) was upregulated in
the cells treated with TGF-beta1, while the expression of ERK and P70S6K was not
altered. To investigate whether CD133 is involved in the TGF-beta1-induced
activation of the ERK/P70S6K signaling pathway in GC cells, immunomagnetic cell
sorting was employed to isolate CD133+ GC cells, and a CD133-expression construct
or CD133-targeting small interfering ribonucleic acids were transfected into
cells to modulate the expression of CD133. Subsequently, the expression of CD133,
ERK, p-ERK, P70S6K, and p-P70S6K was analyzed by western blotting. The CD133+
cells displayed a high expression of p-ERK and p-P70S6K. Furthermore, SGC7901 GC
cells were treated with U0126, an inhibitor of the ERK signaling pathway, to
assess whether CD133 is upstream of ERK/P70S6K. The results showed that the
expression of p-ERK and p-P70S6K was downregulated in the cells treated with
U0126, while the expression of CD133 remained unaltered. The above preliminary
results showed that CD133 likely mediates the TGF-beta1-induced activation of the
ERK/P70S6K signaling pathway in human GC cells. To further understand the
mechanism of regulation of the ERK/P70S6K signaling pathway by CD133, the
expression of CD133 was modulated by transfecting cells with CD133-expression
constructs or CD133-targeting small interfering ribonucleic acids. Results
indicated that overexpression and silencing of CD133 directly increased and
decreased the expression of p-ERK and p-P70S6K, respectively. Therefore, we
hypothesized that CD133 mediates the TGF-beta1-induced activation of the
PI3K/ERK/P70S6K signaling pathway in human GC cells.
PMID- 29344156
TI - Effects of syndecan-1 on the expression of syntenin and the migration of U251
glioma cells.
AB - Glioma is the most frequently occuring primary brain tumor. Syndecan-1 (SDC1)
expression is related to poor prognosis of numerous human malignancies including
glioma. Syndecan binding protein (SDCBP) is an important partner for SDC1. The
present study investigated whether SDC1 and SDCBP are expressed in glioma and
their functions on glioma cell migration. An immunohistochemical assay revealed
that SDC1 and SDCBP were expressed and were positively related to malignant level
of glioma (SDC1, rs=0.576, P=0.001; SDCBP, rs=0.661, P<0.001). Moreover, the
protein levels of SDC1 were positively correlated with those of SDCBP in glioma
tissues (rs=0.628, P=0.001). In U251 glioma cells, protein levels of SDC1 and
SDCBP were both upregulated in U251 cells with SDC1 overexpression, while
downregulated with SDC1 knockdown. Transwell assay and scratch-wound healing
assay showed that SDC1 overexpression significantly increased U251 cell
migration, while SDC1 knockdown had the opposite effects. Rac1 activity, signal
transducer and activator of transcription 3 (STAT3) phosphorylation, as well as
expression of matrix metalloproteinase 2 (MMP2) and MMP9 was significantly
increased by SDC1 overexpression, while was decreased by SDC1 knockdown. In
conclusion, SDC1 overexpression upregulated SDCBP expression, and promoted glioma
cell migration via Rac1 activation.
PMID- 29344157
TI - Expression and clinical significance of programmed death-1 on lymphocytes and
programmed death ligand-1 on monocytes in the peripheral blood of patients with
cervical cancer.
AB - The programmed death-1 (PD-1) signaling pathway serves a critical role in immune
regulation and tolerance by suppressing the activation and proliferation of T
cells. The aim of the present study was to investigate the effect of PD-1 and
programmed death-ligand 1 (PD-L1) on the development of cervical carcinoma and
cervical intraepithelial neoplasia (CIN). A total of 40 healthy controls (HC), 40
patients with CIN and 66 newly diagnosed cervical cancer patients were recruited.
The expression level of PD-1 expression on peripheral cluster of differentiation
(CD)4+ and CD8+ T cells and PD-L1 on monocytes was analyzed by flow cytometry.
The expression level of soluble PD-L1 in serum was determined by an ELISA. The
results of the present study demonstrated that the PD-1 expression level on CD4+
and CD8+ T cells was significantly increased in CIN and cervical cancer, compared
with that in HC. In addition, the PD-1 expression level on CD4+ and CD8+ T cells
was increased in cervical cancer, compared with that in CIN. However, the
expression level of PDL-1 on CD14+ monocytes was increased in cancer and CIN, but
limited in cancer and CIN. In addition, PD-1 expression on CD4+ T cells was
positively associated with PD-1 expression on CD8+ T cells in cervical cancer
(P<0.05). Further analyses revealed that the proportion of PD-1 on CD4+ and CD8+
T cells were positively associated with tumor stages. However, no difference in
the degree of soluble PD-1 among cancer, CIN and HC cells was revealed. The
results suggested that the PD-1 signaling pathway is involved in the development
of CIN and cervical cancer.
PMID- 29344158
TI - Construction of the POT1 promoter report gene vector, and the effect and
underlying mechanism of the POT1 promoter in regulating telomerase and telomere
length.
AB - By using human genomic DNA as a template to clone protection of telomere 1 (POT1)
promoter gene segments and construct the POT1 promoter luciferase report gene
vector (pGL3-Control-POT1-promoter), the association between POT1, and the
regulation of telomerase and telomere length was investigated. In the present
study, two recombinant luciferase report gene vectors were constructed, which
included different regions of the POT1 promoter. The plasmids were transformed
into DH5alpha and the positive clones were obtained. The two plasmids termed as
pGL3-Control-POT1-promoter-1 and pGL3-Control-POT1-promoter-2, were confirmed
using restriction enzyme analysis and sequencing. They were separately and
transiently transfected into four types of human tumor cells (A549, H460, HepG2
and HeLa). The transcriptional activities of the POT1 promoter were verified
using the dual-luciferase assay. The relative expression of POT1 and human
telomerase reverse transcriptase (hTERT), and telomere length were analyzed using
quantitative polymerase chain reaction in the four types of non-transfected tumor
cells. Using SPSS software, correlations between POT1 promoter activity, and POT1
expression, hTERT expression and telomere length were analyzed. Two POT1 promoter
fragments (POT1-promoter-1 and -2) were successfully constructed into the pGL3
Control luciferase report gene vector. POT1-promoter-1 exhibited significantly
stronger transcription activity compared with POT1-promoter-2. The results of the
partial correlation and linear regression analyses were similar: POT1 promoter
activity was identified to be significantly and positively correlated with POT1
expression and telomere length (partial correlation coefficients, both P<0.05;
linear regression, both P<0.01). However, POT1 promoter activity and hTERT
expression were significantly negatively correlated (both P<0.05). The results
obtained in the present study suggest that the POT1 promoter influences telomere
length. Furthermore, these data indicated that POT1 promoter activity and POT1,
as well as telomere length, may be a useful biomarker for tumor detection and
future patient prognosis.
PMID- 29344159
TI - p38 predicts depression and poor outcome in esophageal cancer.
AB - p38 mitogen-activated protein kinase (MAPK) signaling has been implicated in the
cancer development and progression. However, the precise mechanism of this
association remains unknown. The aim of the present study was to evaluate the
association between p38 and cancer progression, including investigations into the
effects on cell proliferation, resistance to thalidomide, indoleamine 2,3
dioxygenase (IDO) expression and prognosis in patients with esophageal cancer.
The present retrospective study included patients with stage I-III esophageal
cancer. A total of 228 patients with esophageal cancer were recruited to analyze
the expression of phosphorylated (p)-p38 and IDO in tumor, and normal tissues
through immunohistochemistry. Depression status was measured using the Zung Self
Rating Depression Scale. P38 cDNA was transfected into esophageal cancer cells to
assess tumor cell viability, sensitivity to thalidomide treatment and IDO gene
expression. Western blotting and flow cytometry was used to analyze protein
expression alterations, and apoptosis in esophageal cancer cells. P-p38 protein
was expressed in 68.9% of cancer tissues, and was significantly associated with
depressive symptoms, tumor recurrence and poor survival of patients. In vitro
experiments revealed that the expression of p-p38 induced esophageal cancer Eca
109 and TE-1 cell viability, and resistance to thalidomide treatment, as well as
in the expression of IDO without the application of lipopolysaccharides. Further
follow-up of patients revealed that depression was also an independent factor for
early recurrence and overall survival rate. Altered p38 MAPK expression was
associated with poor outcome in patients with esophageal cancer. p38 may be a
potential biomarker for the prediction of depressive symptoms and prognosis in
patients with esophageal cancer.
PMID- 29344160
TI - The role of computed tomography and magnetic resonance imaging in diagnosing
clear cell ameloblastoma: A case report.
AB - Ameloblastoma is the most common and clinically relevant type of odontogenic
tumor. Clear cell odontogenic carcinoma is histologically characterized by solid
sheets and nests of clear cells, whereas clear cell ameloblastoma (CCAM) is
histologically characterized by an ameloblastomatous component intermixed with an
extensive clear cell component. A total of 12 reports have been published on the
histological etiology for CCAM; however, no reports have made regarding the
detailed computed tomography and/or magnetic resonance imaging features of tumors
of this type. The present study describes a case of a well-circumscribed 20-mm
radiolucent lesion of the anterior mandible that was misdiagnosed as a clear cell
odontogenic carcinoma. The study describes the detailed radiological
characteristics of a case of CCAM.
PMID- 29344161
TI - UVB radiation represses CYLD expression in melanocytes.
AB - CYLD lysine 63 deubiquitinase (CYLD) was originally identified as a tumor
suppressor that is mutated in familial cylindromatosis. Unlike in
cylindromatosis, downregulation of the deubiquitinase CYLD in melanoma, a highly
aggressive tumor, is not caused by mutations in the CYLD gene, but rather by a
constitutive and high expression of the snail family transcriptional repressor 1
(SNAIL1). A reduced CYLD level leads to B-cell lymphoma-3/p50/p52-dependent
nuclear factor-kappaB activation, which in turn triggers the expression of genes
such as cyclin D1 and N-cadherin. Elevated levels of cyclin D1 and N-cadherin
promote melanoma proliferation and invasion. By analyzing the regulation of CYLD
expression in melanocytes, the present study identified a signaling pathway that
is regulated in response to ultraviolet B (UVB) radiation in melanocytes. UVB
light leads to an extracellular signal-regulated kinase-mediated induction of
SNAIL1 and subsequent downregulation of CYLD expression in normal human
epithelial melanocytes. The UVB-mediated suppression of CYLD in melanocytes may
have a key role in the reaction to UV stimuli, and may also potentially be
involved in the early malignant transformation processes.
PMID- 29344162
TI - Effects of rat bone marrow-derived mesenchymal stem cells on breast cancer cells
with differing hormone receptor status.
AB - Breast cancer is a heterogeneous disease that can be classified into several
molecular intrinsic subtypes according to hormone markers, including estrogen
receptor, progesterone receptor and human epidermal growth factor receptor-2.
Breast cancer cases with different hormone status vary with respect to patient
morbidity, metastasis organotropism and disease progression. It is well known
that the most preferential relapse site of breast cancer is in the bone, but the
metastatic incidence is markedly higher in hormone receptor-positive cancer
compared with that in hormone receptor-negative cancers. Bone marrow-derived
mesenchymal stem cells (BMSCs) perform important roles at the site of metastasis;
however, the effects in different tumors or tumor subtypes are controversial. The
present study aimed to explore the various effects of BMSCs on the biological
characteristics of different hormone receptor statuses. BMSCs were obtained from
female rats and characterized by cell lineage-specific antigens. The MCF-7 and
MDA-MB-231 breast cancer cell lines, which are hormone receptor-positive and
negative, respectively, were employed in the present study. The cancer cells were
co-cultured with BMSCs, and changes in the biological characteristic of cell
growth, apoptosis, migration and epithelial-mesenchymal transition (EMT) were
assessed. BMSCs exhibited chemotactic attraction to MCF-7, promoted the
proliferation of MCF-7 cells and reduced MCF-7 cell apoptosis. By contrast, BMSCs
exerted no marked effects on these behaviors of MDA-MB-231 cells. However,
following co-culture with BMSCs, the migratory ability was enhanced in the two
cell lines. Furthermore, the expression of epithelial markers (epithelial
cadherin and occludin) was decreased, and mesenchymal marker vimentin was
markedly increased in the two cell lines. Notably, the migratory ability of MDA
MB-231 cells was attenuated compared with that of MCF-7 cells. The results from
the present study indicated that BMSCs may favor receptor-positive cancer cell
proliferation in bone and promote enhanced invasiveness of receptor-negative
compared with receptor-positive cancer cells.
PMID- 29344163
TI - Clinical characteristics and treatment outcomes of parathyroid carcinoma: A
retrospective review of 234 cases.
AB - Parathyroid carcinoma (PC) is one of the rarest known types of cancer and has a
moderate prognosis, with estimated 5- and 10-year overall survival rates between
78-85% and between 49-70%, respectively. To raise awareness of this disease, and
to optimize its diagnosis, clinical management and prognosis, the present study
retrospectively reviewed 234 cases of PC. A total of 226 cases of PC, which were
archived between 1984 and 2015 in the three major databases of the Chinese
population, were retrieved and pooled with the 8 cases diagnosed and treated at
the Department of Thyroid Surgery of The First Hospital of Jilin University
(Changchun, China) between June 2008 and December 2015. The clinicopathological
features, diagnosis, surgical procedures and outcomes of these cases of PC were
investigated. The review revealed that misdiagnosis has been a considerable
issue, with >80% of the patients misdiagnosed prior to surgery, and the accuracy
of intraoperative diagnosis based on frozen sections was only 15.04%. The use of
radical resection as first-line therapy significantly improved the disease-free
survival by ~8 years (log-rank, 20.956; P<0.001); and, at relapse, reoperation
prolonged patient survival by ~7 years (log-rank, 35.322; P<0.001). Consistently,
a Cox proportional hazards analysis indicated that radical resection as a first
line therapy reduced the risk of postoperative recurrence (P=0.030), and that
reoperation following recurrence significantly improved patient survival
(P=0.030). The 5- and 10-year cumulative disease-specific survival rates of the
cases of PC were 83 and 67%, respectively. Notably, an increased mortality rate
was observed among males with PC compared with female patients with PC. In
summary, in the past 32 years (1984-2015), the majority of patients with PC have
been misdiagnosed. Performing radical resection as the first-line therapy
significantly reduces recurrence and improves patient survival time; and,
following relapse, subsequent surgery has also been demonstrated to be an
effective approach.
PMID- 29344164
TI - Mastl overexpression is associated with epithelial to mesenchymal transition and
predicts a poor clinical outcome in gastric cancer.
AB - Microtubule-associated serine/threonine kinase like (Mastl) is deregulated in a
number of types of human malignancy and may be a kinase target for cancer
treatment. The aim of the present study was to determine the Mastl expression in
gastric cancer and to clarify its clinical and prognostic significance.
Immunohistochemistry was performed on a cohort of 126 postoperative gastric
cancer samples to detect the expression of Mastl and two epithelial to
mesenchymal transition (EMT) markers, epithelial-cadherin and Vimentin. The chi2
test, Kaplan-Meier estimator analysis and Cox's regression model were used to
analyze the data. Upregulated Mastl protein expression was observed in the
gastric cancer tissues compared with that in the adjacent non-cancerous gastric
tissues. Increased Mastl expression was identified in 54/126 (42.9%) gastric
cancer samples, and was significantly associated with lymph node metastasis,
tumor relapse, EMT status and poor overall survival. Additional analysis
demonstrated that the Mastl expression level stratified the patient outcome in
stage III, but not stage II tumor subgroups. Cox's regression analysis revealed
that increased Mastl expression was an independent prognostic factor for patients
with gastric cancer. Mastl expression may be a valuable prognostic marker and a
potential target for patients with gastric cancer.
PMID- 29344165
TI - Overexpression of forkhead box M1 and urokinase-type plasminogen activator in
gastric cancer is associated with cancer progression and poor prognosis.
AB - Forkhead box M1 (FOXM1) and urokinase-type plasminogen activator (uPA) are
overexpressed and associated with the pathogenesis of multiple types of human
malignancy. The aims of the present study were to investigate FOXM1 and uPA
expression levels in human gastric cancer using tissue microarray techniques;
determining their association with clinicopathological characteristics as well as
their prognostic value. Tissue microarray blocks, comprising 436 gastric cancer
cases and 92 non-cancerous adjacent normal gastric tissues, were analyzed for
FOXM1 and uPA protein expression levels using immunohistochemistry. The results
were analyzed statistically in association with various clinicopathological
characteristics and overall survival rates. FOXM1 and uPA were detected in 78.67
(343/436) and 83.26% (363/436) of cancer samples, respectively. FOXM1 and uPA
were not expressed in the 92 normal gastric tissue samples. In gastric cancer,
FOXM1 and uPA levels were associated with tumor size, depth of invasion, tumor
node-metastasis (TNM) stage, lymph node metastasis, vessel invasion and distant
metastases. The overall survival rate was significantly decreased in patients
expressing FOXM1 and uPA compared with FOXM1- and uPA-negative patients. Coxs
multivariate analysis revealed that age, depth of invasion and expression levels
of FOXM1 and uPA are independent predictors of survival in patients with gastric
cancer. These results indicated that increased FOXM1 and uPA expression levels
are associated with the invasive and metastatic processes in human gastric
cancer, and inversely associated with patient prognosis. Therefore, FOXM1 and uPA
may serve as novel prognostic markers independent of, but supplementing, the TNM
staging system.
PMID- 29344166
TI - Identification and functional analysis of risk-related microRNAs for the
prognosis of patients with bladder urothelial carcinoma.
AB - The aim of the present study was to investigate risk-related microRNAs (miRs) for
bladder urothelial carcinoma (BUC) prognosis. Clinical and microRNA expression
data downloaded from the Cancer Genome Atlas were utilized for survival analysis.
Risk factor estimation was performed using Cox's proportional regression
analysis. A microRNA-regulated target gene network was constructed and presented
using Cytoscape. In addition, the Database for Annotation, Visualization and
Integrated Discovery was used for Gene Ontology (GO) and Kyoto Encyclopedia of
Genes and Genomes pathway enrichment, followed by protein-protein interaction
(PPI) network analysis. Finally, the K-clique method was applied to analyze sub
pathways. A total of 16 significant microRNAs, including hsa-miR-3622a and hsa
miR-29a, were identified (P<0.05). Following Cox's proportional regression
analysis, hsa-miR-29a was screened as a prognostic marker of BUC risk (P=0.0449).
A regulation network of hsa-miR-29a comprising 417 target genes was constructed.
These target genes were primarily enriched in GO terms, including collagen fibril
organization, extracellular matrix (ECM) organization and pathways, such as focal
adhesion (P<0.05). A PPI network including 197 genes and 510 interactions, was
constructed. The top 21 genes in the network module were enriched in GO terms,
including collagen fibril organization and pathways, such as ECM receptor
interaction (P<0.05). Finally, 4 sub-pathways of cysteine and methionine
metabolism, including paths 00270_4, 00270_1, 00270_2 and 00270_5, were obtained
(P<0.01) and identified to be enriched through DNA (cytosine-5)-methyltransferase
(DNMT)3A, DNMT3B, methionine adenosyltransferase 2alpha (MAT2A) and spermine
synthase (SMS). The identified microRNAs, particularly hsa-miR-29a and its 4
associated target genes DNMT3A, DNMT3B, MAT2A and SMS, may participate in the
prognostic risk mechanism of BUC.
PMID- 29344167
TI - Analysis of IMP3 expression in primary tumor and stromal cells in patients with
colorectal cancer.
AB - Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an oncofetal
protein upregulated in tumor cells during carcinogenesis. The aim of the present
study was to investigate the expression status of IMP3 in colorectal cancer (CRC)
tissues and its clinical significance. Immunostaining was performed in 130 CRC
samples, the association of IMP3 expression with clinicopathological
characteristics was assessed and 58 patients were selected for survival analysis.
To the best of our knowledge, the present study describes for the first time the
expression of IMP3 in tumor stromal components of CRC. Stromal expression of IMP3
was detected in 24/130 (18.5%) CRC tissue specimens and was associated with tumor
node-metastasis (TNM) stage (stage III-IV, P=0.003), lymph node metastasis
(P=0.006), lympho-vascular invasion (P=0.003), tumor border (P=0.013). Tumoral
expression of IMP3 was detected in 94/130 (72.3%) of CRC specimens and was
associated with T classification (T3-T4, P=0.027), tumor-node-metastasis (TNM)
stage (stage III-IV, P=0.011), lymph node metastasis (P=0.048), tumor budding
(>10 buds, P=0.005). Further study indicated that patients with IMP3 expressed in
tumor cells and tumor stroma tend to have poorer overall survival rates (P=0.02
and P=0.06, respectively). Moreover, tumoral expression of IMP3 and TNM stage
were identified to be independent prognostic factors in CRC. IMP3 was not only
expressed in tumor cells but also in stroma cells. Stromal expression of IMP3 was
associated with lymph node metastasis and advanced tumor TNM stage. Moreover, the
survival analysis indicated that there is a significant association between IMP3
expression in tumor cells and a poorer overall survival rate in patients with
CRC. The expression of IMP3 maybe a predicted factor for CRC patient.
PMID- 29344168
TI - MiR-124 inhibits invasion and induces apoptosis of ovarian cancer cells by
targeting programmed cell death 6.
AB - Epithelial ovarian cancer remains the most common type of malignant tumor of the
female reproductive system worldwide. Routine surgery and chemotherapy are the
best treatments available for patients with ovarian cancer; however, almost 40%
of ovarian cancer cases are intractable, with poor 5-year survival rates.
MicroRNAs (miRNA) are endogenous small non-coding RNA molecules that function in
transcriptional and post-transcriptional regulation of gene expression in various
cellular processes. Recent studies demonstrated that microRNA (miR)-124 was
downregulated in numerous types of tumors; however, the function and mechanism
underlying miR-124 in epithelial ovarian cancer remain unclear. The present study
revealed that miR-124 may be significantly downregulated in epithelial ovarian
cancer. Using prediction algorithms and luciferase reporter gene assays, the
present study identified and confirmed programmed cell death 6 (PDCD6) as a
novel, direct target of miR-124. Overexpression of miR-124 suppressed PDCD6
expression, inhibited cell proliferation, migration and invasion, and induced
apoptosis in SKOV3 and OCVAR3 cells in vitro. In the present study,
overexpression of PDCD6 in epithelial ovarian cancer cells co-transfected with
miR-124 effectively reversed the miR-124-induced apoptosis. Therefore, the
results of the present study suggested that miR-124 is a tumor suppressor miRNA
and a potential target for future treatment of ovarian malignant neoplasms.
PMID- 29344169
TI - Bortezomib overcomes the negative prognostic impact of renal impairment in a
newly diagnosed elderly patient with multiple myeloma: A case report.
AB - Multiple myeloma (MM) is a common B-cell hematological malignancy in the clinic.
Bortezomib is the first-in-class proteasome inhibitor that has been approved for
the treatment of patients with MM in the bone marrow. The present study report
the case of an 83-year-old man who showed marked weakness, fatigue and a poor
appetite. The patient was admitted to the Department of Nephrology due to severe
renal impairment (RI). Immunofixation electrophoresis indicated a lambda light
chain-positive status. There were 19.2% plasmablasts and proplasmacytes in the
bone marrow. Positivity for the cell surface markers cluster of differentiation
(CD)13, CD33, CD38 and human leukocyte antigen-antigen D-related was detected by
flow cytometry. The patient was diagnosed with MM, lambda light chain type, stage
IIIB, and received bortezomib and dexamethasone regimen chemotherapy. RI was
improved following the chemotherapy, and plasmablasts and proplasmacytes were
almost eliminated. The Hb level was maintained at ~90 g/l. Overall, the present
case report suggests that bortezomib may be safe and effective for elderly
patients, even those >80 years of age, with severe RI.
PMID- 29344170
TI - Phosphorylation of Ser6 in hnRNPA1 by S6K2 regulates glucose metabolism and cell
growth in colorectal cancer.
AB - Abnormal glucose metabolism is critical in colorectal cancer (CRC) development.
Expression of the pyruvate kinase (PK) M2 isoform, rather than the PKM1 isoform,
serves important functions in reprogramming the glucose metabolism of cancer
cells. Preferential expression of PKM2 is primarily driven by alternative
splicing, which is coordinated by a group of splicing factors including
heterogeneous nuclear ribonucleoprotein (hnRNP)A1, hnRNPA2 and RNA binding motif
containing. However, the underlying molecular mechanisms associated with cancer
cell expression of PKM2, instead of PKM1, remain unknown. The mRNA levels of PKM
isoform and glucose metabolism were analyzed in CRC cells. The results of the
present study indicated that S6 kinase 2 (S6K2) promotes glycolysis and growth of
CRC cells by regulating alternative splicing of the PKM gene. In addition,
chromatin immunoprecipitation assay indicated that S6K2 phosphorylation of Ser6
of hnRNPA1 facilitated hnRNPA1 binding to the splicing site of the PKM gene. As a
result, cancer cells preferentially expressed the PKM2 isoform, instead of the
PKM1 isoform. Furthermore, Cox regression analysis demonstrated that the
phosphorylation of Ser6 of hnRNPA1 was a predictor of poor prognosis for patients
with CRC. Therefore, the results of the present study revealed that the
phosphorylation of Ser6 in hnRNPA1 by S6K2 was a novel mechanism underlying
glucose metabolic reprogramming, and suggested that S6K2 is a potential
therapeutic target for CRC treatment.
PMID- 29344171
TI - DEPDC7 inhibits cell proliferation, migration and invasion in hepatoma cells.
AB - DEP Domain Containing 7 (DEPDC7) is highly and specifically expressed in normal
liver tissue, belonging to the class of genes of liver-selective cell
communication. Although the function of DEPDC7 remains poorly understood, its
expression is decreased in liver cancer compared with normal liver tissues. It
has previously been demonstrated that knockdown of DEPDC7 promotes cell growth, S
phase entry and cell mobility and invasion in HepG2 cells. In the present study,
it was shown that DEPDC7 expression is downregulated in four hepatoma cell lines
(SMMC-7721, Huh-7, SK-Hep-1 and HepG2) and 48 hepatoma tissues, determined using
western blot and immunohistochemical analysis. When DEPDC7 is overexpressed in
hepatoma cell lines (SK-Hep-1 and Huh-7), it inhibits cell proliferation and cell
growth; inhibits cell cycle entry; and inhibits cell motility and invasion. These
results, together with the results of knockdown experiments, demonstrate that
DEPDC7 may have an important role in hepatoma cells growth and metastasis and
suggest it could be a therapeutic target; however, in vitro studies are required
to validate this hypothesis.
PMID- 29344172
TI - Potential factors influencing the development of oral tongue squamous cell
carcinoma in young mature patients: Lingual position of the mandibular second
molar and narrow tongue space.
AB - The lingual position of the mandibular second molar and narrow tongue space are
associated with oral tongue squamous cell carcinoma (OTSCC) development in young
mature patients. The present study aimed to assess the role of the mandibular
second molar position and tongue space in young mature patients with OTSCC. The
medical records of 21 patients with OTSCC aged <50 years, who had an intact
mandibular second molar and had undergone computed tomography (CT) imaging
between April 2009 and December 2015 at the Section of Maxillofacial Surgery in
Tokyo Medical and Dental University, were retrospectively examined. As controls,
21 sex-matched patients of a similar age to the patients in the OTSCC group, and
with a height and weight within 5% of those of the OTSCC group, were collected.
The location of the mandibular second molar on the affected side and area of the
tongue space were determined using coronal and axial CT images. Mann-Whitney U
test analysis revealed that the location of the mandibular second molar and the
area of the tongue space differed significantly between young mature patients
with OTSCC and the controls. The present study thus revealed that the lingual
position of the mandibular second molar and the narrow tongue space may be
potential factors influencing OTSCC development in young maturity.
PMID- 29344173
TI - RASAL1 inhibits HepG2 cell growth via HIF-2alpha mediated gluconeogenesis.
AB - RAS protein activator like 1 (RASAL1) is a member of the RAS GTPase-activating
protein (GAP) family, and has been identified as a tumor suppressor in various
types of cancer. In the present study, it was determined that decreased levels of
RASAL1 were accompanied by a higher pathological stage and larger tumor size in
human liver cancer. Therefore, it was hypothesized that RASAL1 may serve an
inhibitory role in liver cancer. In the present study, the following was
demonstrated: i) Exogenous expression of RASAL1 may inhibit the proliferation and
invasion ability of HepG2 cells; ii) overexpression of RASAL1 may downregulate
HIF-2alpha transcription activity and HIF-2alpha-mediated gluconeogenesis through
extracellular signal-related kinase 1/2 activation; iii) RASAL1 may reduce the
xenograft tumor size in nude mice by inhibiting the expression of hypoxia
inducible factor (HIF)-2alpha and gluconeogenesis enzymes. These data suggest
that the RASAL1/HIF-2alpha axis may serve an essential role in the growth of
HepG2 cells, and that this signaling cascade may be a novel therapeutic target
for the treatment of liver cancer.
PMID- 29344174
TI - Expression profile of cytokines in gastric cancer patients using proteomic
antibody microarray.
AB - Gastric cancer (GC) is often a deadly disease due to the late diagnosis and
chemoresistance that characterizes many cases of this disease. The aim of this
study was to explore a panel of candidate cytokines as diagnostic and predictive
biomarkers for GC. Sixteen tissue samples of GC and adjacent noncancerous mucosa
were selected from GC patients (n=8) for antibody microarray analysis. Proteomic
chip-based analysis was performed to simultaneously identify 507 cytokines using
a cytokine antibody array in the gastric tissues to screen for differential
proteins related in cases of GC. Fold changes of protein expression >2.0 or <0.5
were considered significant. The proteins that showed significant differences in
levels between the cancerous and non-cancerous samples were analyzed using
bioinformatics analysis. One hundred and five cytokines that were significantly
different (p<0.05) between GC tissues and normal gastric mucosa were identified.
Gene Ontology (GO) enrichment analysis showed that these differentially expressed
proteins are involved in many biological and immunological processes, mainly in
response to stress, chloroplast thylakoid membrane, vacuole, photosynthesis,
aspartic-type endopeptidase activity and flavin adenine dinucleotide binding.
Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that
these proteins mainly were involved in the process of cytokine-cytokine receptor
interaction, transforming growth factor-beta (TGF-beta) signaling pathway,
pathways in cancer, tumor necrosis factor (TNF) signaling pathway, and mitogen
activated protein kinase (MAPK) signaling pathway. These findings suggest that
the differentially expressed proteins could be associated with GC in patients.
Further study of these cytokines may provide a promising approach for diagnosis,
classification and prognosis of GC.
PMID- 29344175
TI - Effects of andrographolide on postoperative cognitive dysfunction and the
association with NF-kappaB/MAPK pathway.
AB - The present study investigated the effects of andrographolide on postoperative
cognitive dysfunction (POCD) in aged rats to gain insight of the underlying
mechanism, which may provide theoretical basis for the clinical application of
andrographolide to prevent POCD in older patients. Thirty aged male rats were
randomly assigned to 3 groups: Control, model and andrographolide groups. The
Morris water maze test was used to examine the spatial memory and learning
ability of the rats postoperatively. The histological alterations of neuronal
cells in the hippocampus were visualized by H&E staining. The serum levels of
neuron-specific enolase (NSE), human soluble protein-100beta (S-100beta) and the
inflammation factors of interluekin (IL)-1beta, IL-6 and TNF-alpha involved in
the nuclear factor kappaB (NF-kappaB)/mitogen-activated protein kinase (MAPK)
signaling pathway were detected by ELISA. The NF-kappaB/MAPK signaling pathway
associated proteins in rat serum were detected by western blotting. Following
andrographolide treatment, the rats significantly gained learning ability after
surgery. Is it ameliorated hippocampal neuronal injury in rats following surgery.
Andrographolide decreased NSE, S-100beta, and the inflammation factors, IL-6, IL
1beta and TNF-alpha in serum. Andrographolide reduced NF-kappaB/MAPK pathway
associated protein expression. Andrographolide ameliorated POCD in aged rats
following surgery. The underlying mechanism may be associated with the
downregulation the inflammatory factors and NF-kappaB/MAPK-associated protein
expression.
PMID- 29344176
TI - Effect of fraxetin on proliferation and apoptosis in breast cancer cells.
AB - The aim of the present study was to examine the effect of fraxetin on
proliferation and apoptosis in the MCF-7 breast cancer cell line. Cell
proliferation was measused using an MTT assay and 4',6-diamidino-2-phenylindole
(DAPI) staining was used to determine shrinkage and condensation. RT-PCR was used
to examine the expression of factor-associated suicide (Fas) and Fas ligand
(FasL) mRNA, and western blot analysis was used to examine Bax and Bcl-2 protein.
MTT showed that the proliferation of MCF-7 cells was significantly inhibited by
fraxetin in a dose-dependent manner. Fraxetin also induced significant
morphological changes of MCF-7 cells, suggestive of apoptosis, whereas DAPI
staining showed that fraxetin caused cell shrinkage and chromatin condensation.
RT-PCR showed that the expression of Fas and FasL mRNA was upregulated by
fraxetin and the western blot analysis revealed that Bax was upregulated and Bcl
2 was downregulated. In conclusion, fraxetin can inhibit the proliferation of MCF
7 cells, induce apoptosis, upregulate Fas, FasL and Bax, and downregulate Bcl-2
to induce apoptosis. These results support the potential therapeutic role for
fraxetin in breast cancer.
PMID- 29344177
TI - Characteristics of nosocomial infection and its effects on the survival of
chemotherapy patients with advanced non-small cell lung cancer.
AB - The present study was planned to investigate the characteristics of nosocomial
infection and its effects on the survival in advanced non-small cell lung cancer
(NSCLC) patients. Retrospective analysis was performed for the 169 chemotherapy
patients with NSCLC and nosocomial infection during hospitalization in Binzhou
City Central Hospital from March, 2013 to January, 2015. In addition, 170
patients without nosocomial infection were also involved as a control group. The
distribution of major drug resistance of Gram-negative (G-) and Gram-positive
(G+) were analyzed. The survival conditions of the patients were analyzed
according to the nosocomial infection occurrence. The risk factors of nosocomial
infection in patients with NSCLC were analyzed by univariate and multivariate
logistic analysis. The percentage of G+ infection was 45.6% while G- infection
was 54.4%. Nosocomial infections were most common in respiratory system. The
median survival time of the observation group was shorter than that of the
control group (P<0.05). G- infection was the most common type of infection in
nosocomial infection of the patients with NSCLC. The occurrence of infection
seriously affected the survival time of patients. Attention is required to the
patients older than 60 years undergoing treatment with glucocorticoids as well as
immunosuppressive agents.
PMID- 29344178
TI - Long non-coding RNA lncTCF7 activates the Wnt/beta-catenin pathway to promote
metastasis and invasion in colorectal cancer.
AB - Long non-coding RNA (Lnc)TCF7 is a novel lncRNA that is involved in
tumorigenesis. Previous studies have revealed that lncTCF7 serves an essential
role in maintaining cancer stem cell self-renewal; however, the functions of
lncTCF7 in colorectal cancer (CRC) remain unknown. Therefore, the present study
aimed to investigate the role of lncTCF7 in CRC. LncTCF7 was upregulated in 52/58
CRC tissues, and its expression correlated with tumor size, lymph metastasis and
tumor-node-metastasis stage in CRC. Knocking down lncTCF7 in colon cancer cell
lines decreased cell proliferation, migration and invasion, while lncTCF7
overexpression showed opposite changes. In addition, lncTCF7 promoted cell
proliferation in vivo. LncTCF7 activated the Wnt/beta-catenin signaling pathway,
which is essential for cancer development. Survival analysis revealed that
patients with higher expression of lncTCF7 had significantly worse prognosis
compared with patients with low expression. These findings indicate that lncTCF7
regulates CRC progression and support the notion of lncTCF7 as a CRC prognostic
marker.
PMID- 29344179
TI - In vivo antitumor activity evaluation of cancer vaccines prepared by various
antigen forms in a murine hepatocellular carcinoma model.
AB - Cancer cell vaccines with strong specificity and low tolerance have been revealed
to be a promising option for oncology treatment. Various antigen forms, including
tumor cell lysate and glutaraldehyde-fixed tumor cells, have been intensively
used in cancer vaccine preparation. However, the most effective antigen form has
not yet been identified. In the present study, the antitumor efficiency of
vaccines prepared by these two antigen forms was systematically investigated.
Murine H22 hepatocellular carcinoma cell lysate and glutaraldehyde-fixed H22
hepatocellular carcinoma cells were conjugated with Freund's adjuvant to prepare
vaccines, H22-TCL and Fixed-H22-CELL, respectively. H22-TCL and Fixed-H22-CELL
were administrated by subcutaneous immunization in prophylactic and therapeutic
strategies. The results of the present study revealed that H22-TCL immunization
induced more significant inhibition on tumor growth and metastasis compared with
Fixed-H22-CELL injection. Furthermore, histopathological observation demonstrated
that H22-TCL vaccine induced larger areas of continuous necrosis within tumors
compared to the Fixed-H22-CELL vaccine, which was associated with the extent of
tumor inhibition. More importantly, the H22-TCL vaccine injection elicited more
evident antigen-specific antibody responses compared with the Fixed-H22-CELL
injection. Splenocytes from H22-TCL vaccinated mice also exhibited a more
significant T lymphocytes proliferation compared with that from Fixed-H22-CELL
treated mice. All the results indicated that whole tumor cell lysate may be a
more effective antigen form in cancer vaccine preparation compared with
glutaraldehyde-fixed tumor cells, which elicited more marked antigen specific
humoral and cellular immune responses resulted with a superior antitumor
efficiency. This would have important clinical signification for cancer vaccine
preparation and serve a role in prompting this to other researchers.
PMID- 29344180
TI - miR-493 inhibits proliferation and invasion in pancreatic cancer cells and
inversely regulated hERG1 expression.
AB - The human ether-a-go-go-related potassium channel 1 (hERG1) is a component of the
voltage-gated Kv11.1 potassium channel, which has been recently indicated to have
a crucial role in the tumorigenesis of multiple tumors, including pancreatic
carcinoma. Pancreatic carcinoma is one of the most malignant human cancer types,
which has an extremely poor prognosis. The present study demonstrated that the
expression levels of hERG1 were markedly elevated in pancreatic cancer tissues
and pancreatic cancer cell lines, and that the abnormal hERG1 expression was
significantly associated with the proliferation and invasion ability of
pancreatic cancer. Furthermore, hERG1 was identified to be a direct target of miR
493, which is generally reduced in pancreatic cancer tissues and cell lines.
These findings provide a novel insight into the regulatory mechanism of miR
493/hERG1 in pancreatic cancer cell proliferation and invasion, which may aid the
development of novel diagnostic and therapeutic strategies for pancreatic cancer
in the future.
PMID- 29344181
TI - L-type amino acid transporter 1 expression is upregulated and associated with
cellular proliferation in colorectal cancer.
AB - Previous studies have shown that the L-type amino acid transporter 1 (LAT1) is
highly expressed in many types of cancer. Upregulated LAT1 expression is
considered to be associated with cancer cell proliferation. In the present study,
we investigated LAT1 expression in 210 patients with colorectal cancer (CRC) and
40 patients with colonic adenoma using an immunohistochemical method, and
analyzed the associations between LAT1 expression and clinicopathological factors
and prognosis. The biological significance of LAT1 was also examined under
conditions with sub-normal amounts of essential amino acids using colon cancer
cell lines. High expression of LAT1 was observed in 152 of 210 CRC patients
(72.4%) and 12 of 40 patients with colonic adenoma (30%), and this difference in
the frequency of LAT1 expression between CRC and adenoma was significant
(P<0.001). High expression of LAT1 was associated with venous invasion (P=0.027).
The restriction of amino acids suppressed cell proliferation in CRC cells with
higher LAT1 expression, while cellular proliferation was not suppressed in the
cells expressing lower levels of LAT1. Mammalian target of rapamycin (mTOR)
expression was also downregulated under restricted availability of amino acids,
suggesting that the restriction of amino acids induced an antitumor effect
through inhibition of the LAT1/mTOR pathway. In summary, the present study
demonstrated that LAT1 expression is frequently upregulated in CRC and is
associated with cancer cell proliferation via the mTOR pathway.
PMID- 29344182
TI - C-reactive protein/albumin and neutrophil/lymphocyte ratios and their combination
predict overall survival in patients with gastric cancer.
AB - Multiple studies have reported the prognostic association of certain inflammatory
factors with various types of cancer. The present study assessed the prognostic
value of the C-reactive protein (CRP)/albumin (Alb) ratio and the
neutrophil/lymphocyte ratio (NLR), separately and in combination, in gastric
cancer (GC). A total of 337 cases pathologically diagnosed with gastric
adenocarcinoma were retrospectively evaluated. The clinicopathological and
prognostic relevance of the CRP/Alb ratio and NLR and their combination were
analyzed. The optimal cut-off values of the CRP/Alb ratio and NLR were 0.38 and
3.14, respectively. High CRP/Alb ratio (>=0.38) and NLR (>=3.14) values were
associated with increased tumor invasion, more distant metastasis and a more
advanced tumor-node-metastasis stage (all P<0.05). In addition, a high NLR value
was also associated with increased tumor size (P=0.02). The CRP/Alb ratio
(>=0.38/<0.38) and NLR (>=3.14/<3.14) were independent prognostic factors for
overall survival time (OS) in GC by multivariate analysis (P=0.005 and P=0.001).
Using the CRP/Alb ratio and NLR classification, patients were stratified into
three subgroups with different OS time (P<0.001), which were identified as
independent prognostic variables in multivariate analysis (P<0.001). The present
study demonstrated that the CRP/Alb ratio and NLR were independent prognostic
factors for OS in patients with GC. The combination of these indexes was
associated with significant prognostic value and may further stratify prognosis.
PMID- 29344183
TI - A patient with chronic myeloid leukemia and situs inversus totalis: A case
report.
AB - In the present study, a case of chronic myeloid leukemia (CML) with complete
situs inversus in a 68-year-old female patient was reported. The patient
presented with general weakness, abdominal distension and tenderness in the right
hypochondrium. A chest X-ray revealed a right-sided heart. Ultrasonography
revealed situs inversus totalis. A bone marrow smear demonstrated CML in the
accelerated phase. Imatinib mesylate was subsequently administered; the patient
stopped taking imatinib mesylate following discharge from the hospital. The
patient presented with dizziness, fatigue, and abdominal distention and pain 1
year subsequently. A bone marrow smear demonstrated CML in the blast crisis
phase; CML had progressed to acute myeloid leukemia (AML) M2a. The patient was
treated with imatinib mesylate and cytarabine. After 5 days, the white blood cell
count had decreased compared with that measured at the time of admission, and the
previous relevant symptoms had disappeared. The patient succumbed to AML 3 months
after discharge from the hospital. Situs inversus totalis is an uncommon
congenital anomaly that often occurs concomitantly with other disorders. The
present study documented, to the best of our knowledge, the second recorded case
of CML in a patient with situs inversus totalis. Previous studies on the
pathogenesis of situs inversus have suggested it is caused by embryonic cells
failing to rotate normally during early embryonic development. Although there are
case reports of situs inversus totalis in patients with cancer, there are few
reports on the association between situs inversus totalis and cancer. The present
study examined a case of CML with situs inversus totalis and assessed whether the
latter may be associated with cancer.
PMID- 29344184
TI - Therapeutic effects of adenovirus-mediated CD and NIS expression combined with
Na131I/5-FC on human thyroid cancer.
AB - Thyroid cancer is the most common type of malignant endocrine tumor diagnosed.
Previous studies have indicated that gene therapy is the most promising and
effective therapeutic method for thyroid cancer. Therefore, in the present study,
Na131I/5-fluorocytosine (5-FC) treatment was combined with cytosine deaminase
(CD, encoded by the CDA gene) and sodium iodide symporter (NIS, encoded by the
SLC5A5 gene) to act together as a therapeutic tool for thyroid cancer. The
present study explored the combined cytotoxic effects of adenovirus-mediated CD
and NIS under the control of the progression elevated gene-3 (PEG-3) promoter (Ad
PEG-3-CD-NIS) with Na131I/5-FC against the human thyroid cancer TT cell line in
vitro. The PEG-3 fragment was obtained by polymerase chain reaction (PCR) using
rat genomic DNA as the template, and then Ad-PEG-3-CDA-SLC5A5 was constructed
using XbaI. TT cells were transfected by recombinant adenovirus. The method of
reverse transcription-quantitative PCR was performed to test the expression of CD
and NIS at the level of transcription. The morphological change was assessed by
fluorescence microscopy and investigated by western blot analysis. An MTT assay
was used to determine the number of living cells inhibited by single or
combination therapies on TT cells. The results indicated that the PEG-3 was
successfully cloned, and was also positively regulated in 293 cells. CDA and
SLC5A5 genes were highly expressed in TT cells. Na131I combined with 5-FC
significantly decreased the human thyroid cancer cells. In conclusion,
combination therapy of Ad-PEG3-CDA-SLC5A5 and Na131I/5-FC induces significantly
more apoptotic characteristics than either single treatment with Ad-PEG-3-CDA
SLC5A5 or Na131I/5-FC, and low doses of Ad-PEG-3-CDA-SLC5A5 enhanced the
cytotoxic effects.
PMID- 29344185
TI - Downregulation of miR-30a is associated with proliferation and invasion via
targeting MEF2D in cervical cancer.
AB - Accumulating studies have revealed that microRNAs serve crucial roles in cancer
development and progression. MicroRNA-30a (miR-30a) has been implicated in
various cancer types. However, the role of miR-30a in cervical cancer remains
unclear. In the current study, a reverse transcription-quantitative polymerase
chain reaction (RT-qPCR) assay revealed that miR-30a was significantly
downregulated in cervical cancer tissues compared with adjacent normal tissues,
and in the cervical cancer cell lines HeLa, SiHa and Ca-Ski compared with GH329
normal cervical epithelial cells. A functional assay using miR-30a mimic
demonstrated that miR-30a could inhibit the growth and invasion of cervical
cancer cells. Additionally, bioinformatics-based prediction and luciferase
reporter assays indicated that MEF2D is a direct target of miR-30a. Transfection
with miR-30a reduced the mRNA expression and protein levels of MEF2D, as
determined using RT-qPCR and western blot analyses. Furthermore, MEF2D expression
was negatively correlated with that of miR-30a in cervical cancers. Overall, the
present study demonstrated that miR-30a functions as a tumor suppressor by
targeting MEF2D in cervical cancer, which may provide the basis for a prognostic
biomarker or therapeutic strategy for cervical cancer.
PMID- 29344186
TI - Downregulation of klotho beta is associated with invasive ductal carcinoma
progression.
AB - Klotho beta (KLB) is a single-pass transmembrane protein measuring 1,043 amino
acids in length that shares 41.2% homology with klotho alpha (KLA). KLB is a co
receptor and key regulator of the fibroblast growth factor receptor 4 (FGFR4)
pathway. KLB interacts with FGFR4 to induce apoptosis and inhibit the
proliferation of hepatoma cells, and KLA has been demonstrated to be a tumor
suppressor in human breast cancer; however, little is known regarding the role of
KLB in breast cancer. In the present study, through an immunohistochemical
analysis of invasive ductal carcinoma tissue arrays, low KLB expression was
identified in invasive ductal carcinoma samples compared with paired adjacent non
tumorous breast tissues (82 cases). In invasive ductal carcinoma tissues, KLB
expression was negatively associated with pathological grade and lymph node
metastasis. In 42 cases of paired microdissected breast specimens, the condition
of the KLB gene allele was examined to determine the loss of heterozygosity
(LOH), and selective LOH was identified at the KLB locus in 57.1% of primary
tumors. These data suggest that KLB may be associated with the progression and
metastasis of invasive ductal carcinoma, and therefore have clinical and
therapeutic importance.
PMID- 29344187
TI - Patuletin induces apoptosis of human breast cancer SK-BR-3 cell line via
inhibiting fatty acid synthase gene expression and activity.
AB - Fatty acid synthase (FASN) is a key enzyme involved in fatty acid biosynthesis
and serves an important role in breast cancer development. The aim of the present
study was to investigate the effects of patuletin on the gene expression and
activity of FASN in the human breast cancer SK-BR-3 cell line, and the apoptotic
effects of patuletin to breast cancer cells. Quantitative reverse transcription
polymerase chain reaction, western blotting and intracellular FASN activity
assays were used to evaluate FASN gene expression, protein expression and
activity in patuletin-treated SK-BR-3 cells. MTT assays and flow cytometry were
used to measure cell growth and cell apoptosis, respectively, following patuletin
treatment. As a result, it was demonstrated that patuletin dose-dependently
reduces FASN expression and intracellular activity in human breast cancer cells,
and induces apoptosis in FASN over-expressing SK-BR-3 cells. Notably, apoptosis
is associated with the reduction of intracellular FASN activity. The present
study demonstrates that patuletin may be considered as a novel natural inhibitor
of FASN, may induce anti-proliferative and pro-apoptotic effects in certain human
breast cancer cells and may be useful for preventing and/or treating human breast
cancer.
PMID- 29344188
TI - High expression of special AT-rich sequence binding protein-1 predicts esophageal
squamous cell carcinoma relapse and poor prognosis.
AB - Previous studies of the roles of special AT-rich sequence binding protein-1
(SATB1) in the development and progression of cancer have suggested that SATB1
promotes cancer cell metastasis. The aim of the present study is to evaluate the
role of SATB1 in the progression and prognosis of esophageal squamous cell
carcinoma (ESCC). ESCC tissues were collected from 102 patients and SATB1 mRNA
expression was measured by reverse transcription-quantitative polymerase chain
reaction. The association between expression of SATB1 mRNA with
clinicopathological features and prognosis was assessed, and the prognosis of
ESCC was evaluated using Kaplan-Meier survival curves. In the 102 ESCC tissues,
SATB1 mRNA expression correlated with the clinical tumor node metastasis stage
(P<0.05), but not with any other clinicopathological features (including age,
gender, tumor differentiation grade, adjuvant radio/chemotherapy, or the
consumption of alcohol and use of cigarettes) (P>0.05). The disease-free survival
(DFS) and overall survival (OS) of patients with high SATB1 expression was
decreased compared with those with low SATB1 expression. The present study
indicated that SATB1 mRNA expression was associated with the postoperative
recurrent and poor prognosis in ESCC. SATB1 may be a novel marker for predicting
the recurrent and worse prognosis of ESCC.
PMID- 29344189
TI - Phosphorylated AKT expression in tumor-adjacent normal tissue is associated with
poor prognosis in patients with hepatocellular carcinoma.
AB - The AKT pathway serves important roles in tumor cell growth. Its overexpression
is associated with poor prognosis in a number of types of cancer; however, the
role of AKT in the role of the pathogenesis of hepatocellular carcinoma (HCC)
remains unclear. The present study was undertaken to explore the clinical
relevance of phosphorylated AKT (p-AKT) in HCC. The level of p-AKT in tumor (TU)
and paired adjacent normal liver (AN) tissue from 202 HCC patients was evaluated
with immunohistochemistry. The results demonstrated that p-AKT was more highly
expressed in TU than in AN tissue. Kaplan-Meier curves and Cox regression
revealed that patients with a high expression of p-AKT (AN) exhibited reduced
overall and relapse-free survival times; this was not observed at a statistically
significant level in p-AKT (TU). Additionally, the high expression of p-AKT (AN)
was positively correlated with hepatitis C virus (HCV) infection in HCC patients.
These results support the hypothesis that AKT activation is a mechanism of HCV
induced hepatocarcinogenesis, suggesting that AKT can be a therapeutic target for
the treatment of recurrent HCC subsequent to surgical resection.
PMID- 29344190
TI - Anticancer effect of triterpenes from Ganoderma lucidum in human prostate cancer
cells.
AB - Ganoderma lucidum, within the Polyporaceae family of Basidiomycota, is a popular
traditional remedy medicine used in Asia to promote health and longevity.
Compounds extracted from G. lucidum have revealed anticancer, antioxidant and
liver protective effects. G. lucidum has been associated with prostate cancer
cells. G. lucidum extracts contain numerous bioactive components; however, the
exact functional monomer is unknown and the role of triterpenes from G. lucidum
(GLT) in prostate cancer remain obscure. The present study investigated the
effects of GLT on cell viability, migration, invasion and apoptosis in DU-145
human prostate cancer cells. The results demonstrated that a high dose (2 mg/ml)
of GLT inhibits cell viability in a dose- and time-dependent manner by the
regulation of matrix metalloproteases. Furthermore, GLT induced apoptosis of DU
145 cells. In general, GLT exerts its effect on cancer cells via numerous
mechanisms and may have potential therapeutic use for the prevention and
treatment of cancer.
PMID- 29344191
TI - Expression and prognostic significance of cyclin-dependent kinase inhibitor 1A in
patients with resected gastric adenocarcinoma.
AB - Cyclin-dependent kinase inhibitor 1A (CDKN1A) is an important cell
cycleregulator, and has been identified to exhibit aberrant expression in various
types of cancer tissues. However, the association between CDKN1A expression level
and prognosis in patients with resected gastric adenocarcinoma (RGA) requires
additional elucidation. In the present study, the CDKN1A expression profile in
RGA tissues obtained from 217 patients were analyzed using immunohistochemistry.
Its prognostic significance was evaluated by using the chi2 test, Kaplan-Meier
curves and the log-rank test, and a multivariate Cox model analysis, during a
median follow-up time of 51 months. The results demonstrated that CDKN1A
expression was significantly correlated with lymph node metastasis (LNM;
P=0.001), recurrence (P<0.001) and overall survival (OS; P<0.001). In addition,
the recurrence-free survival (RFS) and OS times were significantly shorter in
patients with low CDKN1A expression compared with those with high CDKN1A
expression (RFS, 20 months vs. 69 months, P<0.001; and OS, 32 months vs. 70
months, P<0.001, respectively). Multivariate analysis additionally confirmed that
low CDKN1A expression was significantly correlated with an increased risk of LNM
(P=0.001), recurrence (P<0.001) and mortality (P<0.001). Therefore, these data
suggest that low expression of CDKN1A has independent prognostic significance
indicative of tumor progression and poor survival in patients with RGA.
Evaluation of CDKN1A expression may assist in determining prognosis in patients
with RGA.
PMID- 29344192
TI - TSLP promotes angiogenesis of human umbilical vein endothelial cells by
strengthening the crosstalk between cervical cancer cells and eosinophils.
AB - Our previous study demonstrated that thymic stromal lymphopoietin (TSLP) secreted
by cervical cancer cells promotes angiogenesis and recruitment, and regulates the
function of eosinophils (EOS). However, the function of TSLP in the crosstalk
between EOS and vascular endothelial cells in cancer lesions remains unknown. The
aim of the present study was to investigate the effect of EOS caused by TSLP in
in vitro angiogenesis of human umbilical vein endothelial cells (HUVECs). The
results of the present study revealed that recombinant human TSLP protein
(rhTSLP) increased the secretion of vascular endothelial growth factor (VEGF),
but not fibroblast growth factors, in HL-60-eosinophils (HL-60E). Compared with
cervical cancer cells (HeLa or CasKi cells) or HL-60E alone, there were increased
levels of interleukin (IL)-8 and VEGF in the co-culture system between cervical
cancer cells, and HL-60E cells. This effect was strengthened by rhTSLP, but
inhibited by inhibiting the TSLP signal with anti-human TSLP or TSLP receptor
neutralizing antibodies. The results of the tube formation assays revealed that
treatment with the supernatant from cervical cancer cells and/or HL-60E resulted
in an increase in angiogenesis in HUVECs, which could be decreased by TSLP or
TSLPR inhibitors. The results of the present study suggested that TSLP derived of
cervical cancer cells may indirectly stimulate angiogenesis of HUVECs, by
upregulating IL-8 and VEGF production, in a co-culture model between cervical
cancer cells and EOS, therefore promoting the development of cervical cancer.
PMID- 29344193
TI - Identification of differentially expressed molecular functions associated with
breast cancer using Gibbs sampling.
AB - The aim of the present study was to identify differentially expressed molecular
functions (DEMFs) for breast cancer using the Gibbs sampling approach. Molecular
functions (MFs) were obtained on the basis of the Bayesian Approach for Geneset
Selection package. Subsequently, MFs were converted into Markov chains (MCs)
prior to calculating their probabilities, utilizing the MC Monte Carlo algorithm.
DEMFs were identified with probabilities >=0.8 and the gene compositions were
studied. Finally, a co-expression network was constructed via the empirical Bayes
method and a pathway enrichment analysis of genes in DEMFs was performed. A total
of 396 MFs were identified and all transformed to MCs. With the threshold, 2
DEMFs (structural molecule activity and protein heterodimerization activity) were
obtained. The DEMFs were comprised of 297 genes, 259 of which were mapped to the
co-expression network. These 297 genes were identified to be enriched in 10
pathways, and ribosome was the most significant pathway. The results of the
present study revealed 2 DEMFs (structural molecule activity and protein
heterodimerization activity) which may be associated with the pathological
molecular mechanisms underlying breast cancer, based on Gibbs sampling.
PMID- 29344194
TI - Chronic myeloid leukemia following repeated diagnostic X-ray exposure for the
treatment of recurrent spontaneous pneumothorax in a patient with ankylosing
spondylitis: A case report and literature review.
AB - Previous studies have indicated that X-ray irradiation may increase the risk of
chronic myeloid leukemia (CML), and the incidence of spontaneous pneumothorax in
patients with ankylosing spondylitis (AS) is higher than in the general
population. Patients with AS usually develop spontaneous pneumothorax several
years after the diagnosis of AS. The present study reports the unusual case and
complicated clinical history of a 29-year-old man with recurrent pneumothorax and
AS, who developed CML following repeated exposure to low doses of radiation via
diagnostic X-rays and chest computed tomography imaging. Pneumothorax was
diagnosed prior to AS in this patient; the present case report highlights the
importance of recognizing AS as a possible underlying cause of recurrent
spontaneous pneumothorax. Patients with AS may be more sensitive to injury via X
ray-derived radiation, and even small diagnostic doses may be associated with
CML. Diagnostic X-ray exposure should therefore be limited to reduce the risk of
radiation-associated malignancies, including CML, particularly in patients with
AS.
PMID- 29344195
TI - Collagen triple helix repeat containing 1 promotes tumor angiogenesis in
gastrointestinal stromal tumors.
AB - Collagen triple helix repeat containing 1 (Cthrc1) is a secreted protein that has
been observed to lead to poorer prognosis by inducing the invasion and metastasis
in different tumors; however, it has not been demonstrated that Cthrc1 is
involved in tumor angiogenesis. Immunohistochemical staining of Cthrc1 and CD31
in gastrointestinal stromal tumor tissue demonstrated that Cthrc1 is associated
with microvascular density. Overexpression of Cthrc1 protein may alter the
properties of human umbilical vein endothelial cells (HUVECs), including
migration, invasion, tubule formation and aortic ring sprouting. Small
interfering RNA-mediated knockdown of Cthrc1 was performed to verify the opposite
effects. Migration and tubule formation induced by Cthrc1 overexpression in
HUVECs was attenuated by inhibition of phosphorylation in extracellular-signal
regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling
pathways. The pro-angiogenic effect of Cthcr1 is associated with increased
phosphorylation of ERK and JNK in HUVECs. Silencing the expression of Cthrc1
protein may be a promising strategy to inhibit tumor angiogenesis.
PMID- 29344196
TI - Downregulated expression of TSHR is associated with distant metastasis in thyroid
cancer.
AB - In differentiated thyroid cancer (DTC), the association between thyroid
stimulating hormone receptor (TSHR) and metastasis, and the underlying molecular
mechanisms remain unclear. The role of TSHR in the epithelial-mesenchymal
transition (EMT) has not yet been reported, to the best of our knowledge. In the
present study, the role of TSHR in the distant metastasis of DTC was
investigated. TSHR was significantly downregulated in well-differentiated thyroid
cancer cells and tissues, and a lack of TSHR promoted thyroid cancer cell
invasion and metastasis by inhibiting the EMT of thyroid cancer cells. In
addition, the prognostic value of TSHR in thyroid cancer was analyzed.
Immunohistochemical analysis of 172 DTC tissues revealed that a lack of
expression of TSHR was associated with distant metastasis and a poor survival
rate. Multivariate analyses demonstrated that TSHR expression was a significant
prognostic factor for distant metastasis and survival time. The results from the
present study demonstrated that TSHR inhibits metastasis through regulating EMT
in vitro, and that a lack of expression of TSHR is a significant independent
factor affecting distant metastasis and poor prognosis in DTC.
PMID- 29344197
TI - Overexpression of CXCR4 promotes invasion and migration of non-small cell lung
cancer via EGFR and MMP-9.
AB - The aim of the present study was to verify whether overexpression of CXC receptor
4 (CXCR4) promotes the invasion and migration of non-small cell lung cancer
(NSCLC) via epidermal growth factor receptor (EGFR) and matrix metallopeptidase-9
(MMP-9), and to detect the association between CXCR4, EGFR and MMP-9. The effects
of overexpression of CXCR4 on lung cancer cell functions were investigated by
migration and invasion assays. Western blotting and zymograph assays were used to
analyze the protein expression levels of EGFR and the production of MMP-9,
respectively. Immunohistochemistry was applied to analyze the expression of EGFR,
CXCR4 and MMP-9 in NSCLC. Statistical analyses were used to detect the
associations among EGFR, CXCR4 and MMP-9 in NSCLC. Finally, survival analyses
were performed. CXCR4 overexpression enhanced cell motility and invasion. CXCR4
also promoted expression of EGFR and elevated MMP-9 production. CXCR4, EGFR and
MMP-9 were highly expressed in NSCLC, and were not identified as associated with
age and sex (P>0.05). However, they were associated with tumor differentiation
and lymph node metastasis (P<0.05). CXCR4, EGFR and CXCR4 expression were
positively associated with one another in NSCLC (P<0.05). In addition, patients
with positive expression of CXCR4, EGFR or MMP-9 in tumors exhibited
significantly shorter overall survival compared with those with negative
expression (P<0.05). In conclusion, CXCR4 overexpression enhanced cell motility
and invasion via EGFR and MMP-9. CXCR4, EGFR and MMP-9 were identified as highly
expressed in NSCLC, and there was positive correlation among them.
PMID- 29344198
TI - Combination of cecropinXJ and LY294002 induces synergistic cytotoxicity, and
apoptosis in human gastric cancer cells via inhibition of the PI3K/Akt signaling
pathway.
AB - The aim of the present study was to investigate the cytotoxic and apoptotic
effects of cecropinXJ against human gastric cancer BGC823 cells, either alone, or
in combination with a specific phosphatidylinositol 3-kinase (PI3K) inhibitor,
LY294002. Cell viability and the apoptosis rate were measured using flow
cytometry with Annexin-V staining. Additionally, the expression levels of several
RAC-alpha serine/threonine kinase (Akt) phosphorylation-associated proteins and
apoptosis-regulating proteins were evaluated by western blot analysis. It was
observed that the combination of cecropinXJ and LY294002 resulted in significant
synergistic cytotoxic and apoptosis effects, as compared with any single agent
alone, in a dose-dependent manner. Corresponding to enhanced apoptosis, the
expression levels of certain apoptosis-regulating proteins were changed, the most
notable being the upregulation of caspase-3, B-cell lymphoma-2 (Bcl-2)-associated
death promotor, Bcl-2 homologous antagonist killer, Bcl-2 interacting killer, Bcl
2-like protein 11, Bcl-2-like protein 4 and cytochrome c, and the downregulation
of phosphorylated-Bad and Bcl-2 proteins. The present study provided a novel
therapeutic regimen for the use of the cecropinXJ in combination with LY294002
for the treatment of gastric cancer.
PMID- 29344199
TI - Expression and prognostic significance of doublecortin-like kinase 1 in patients
with hepatocellular carcinoma.
AB - Doublecortin-like kinase 1 (DCLK1), a putative cancer stem cell marker in
intestinal and pancreatic tumors, is associated with tumor pathogenesis and
progression, and poor survival outcomes in numerous types of cancer. However,
DCLK1 expression and its prognostic value remain unclear in hepatocellular
carcinoma (HCC). In the present study, the expression of DCLK1 was assessed using
immunohistochemistry in 96 resected HCC and 68 adjacent tissue specimens. The
staining intensity and the percentage of stained cells were scored on a scale of
0-3 and 0-4, respectively. Tissue was defined as positive for DCLK1 if the
composite multiple score was >3. Cytoplasmic expression of DCLK1 was observed in
HCC and adjacent tissue specimens with an expression rate of 81% (78/96) and 74%
(50/68), respectively; the median score was 4.6 and 3.9, respectively, and no
statistically significant difference was observed between HCC and adjacent
tissues (P=0.087). DCLK1 expression was positively associated with intrahepatic
metastasis (P=0.035). Furthermore, univariate analysis revealed that DCLK1
expression was significantly associated with poor disease-free survival (DFS) and
overall survival (P=0.024 and 0.034). Multivariate analysis also demonstrated
that DCLK1 expression was an independent prognostic factor for DFS in HCC
(P=0.019; hazard ratio, 1.546; 95% confidence interval, 1.330-1.725). Stratified
Kaplan-Meier survival curves revealed that DCLK1 expression predicted poorer DFS
with respect to positivity for three characteristics: Portal venous metastasis,
intrahepatic metastasis, and cirrhosis (P=0.020, P=0.007 and P=0.017,
respectively). Collectively, the results of the present study suggested that
DCLK1, functioning as a tumor promoter, is frequently overexpressed in HCC, and
that DCLK1 expression is associated with poor DFS in patients with HCC. DCLK1 may
represent a promising therapeutic target in HCC and requires further study.
PMID- 29344200
TI - Molecular pathological predictive diagnostics in a patient with non-small cell
lung cancer treated with crizotinib therapy: A case report.
AB - Lung cancer is one of the most common malignant cancers in the Czech Republic in
men, with the highest mortality rate of all the malignant diseases. The
development of biological treatment enables study into novel personalized
treatment options. This type of treatment is usually of high quality, and is
often demanding of predictive and biopsy diagnostics, which is dependent on the
quality of the collected material and close cooperation among particular
departments. The present study describes the complete biopsy and predictive
examinations performed in a male patient with lung adenocarcinoma, with an
emphasis on the logistics of the whole process and the application of the
tyrosine kinase inhibitors, crizotinib and LDK378. The patient experienced a long
overall survival time of 28 months from diagnosis.
PMID- 29344201
TI - Elevation of serum CEA and CA15-3 levels during antitumor therapy predicts poor
therapeutic response in advanced breast cancer patients.
AB - The aim of the present study was to assess the correlation between therapeutic
response and carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15
3) levels in advanced breast cancer patients with non-assessable lesions or
stable disease (SD) according to the Response Evaluation Criteria in Solid
Tumors. A total of 232 female patients with recurrent tumors following radical
mastectomy were recruited, including 76 patients with non-assessable lesions and
60 patients with SD. The correlation between CEA and CA15-3 changes, progression
free survival (PFS) and therapeutic response were analyzed in the non-assessable
and SD patient groups. For all subjects, the association between the patients'
serum tumor markers levels and the clinical presentation of the tumor, as well as
the correlation between initial tumor marker levels and PFS, were analyzed. An
increase in CEA (an increment of >2 ng/ml) or CA15-3 levels (an increase of >15
U/ml) following the second cycle of treatment correlated with shorter PFS in both
non-assessable and SD patients, and with poor clinical outcome in SD patients.
High CA15-3 levels correlated with hormone receptor-positive tumors, multiple
metastases and liver metastases. Bone metastases correlated with high levels of
both CEA and CA15-3. Relatively low CEA and CA15-3 concentrations were associated
with triple-negative and locally invasive tumors. High CEA and CA15-3 levels at
the beginning of relapse correlated with shorter PFS. The present study
illustrates that CEA and CA15-3 levels correlate with several factors in
recurrent breast cancer patients. Elevated levels of CEA and CA15-3 at the
beginning of relapse may predict shorter PFS. Furthermore, elevation of CEA and
CA15-3 levels following the second therapeutic cycle predict poor therapeutic
response in patients with non-assessable lesions and SD. Our findings suggest
that alterations in CEA and CA15-3 levels can predict therapeutic response in
advanced breast cancer patients.
PMID- 29344202
TI - Metformin in combination with cisplatin inhibits cell viability and induces
apoptosis of human ovarian cancer cells by inactivating ERK 1/2.
AB - Metformin protects against insulin resistance by restoring insulin sensitivity
and may also possess anticancer activity. The aim of the present study was to
investigate the effects of metformin alone or combined with cisplatin (DDP) on
the cell viability and apoptosis of HO-8910 human ovarian cancer cells, and to
investigate metformin as a potential novel therapeutic for treating ovarian
cancer. The viability of HO-8910 cells was assessed using a cell proliferation
and cytotoxicity assay following treatment with different concentrations of
metformin (0.01, 0.5, 1, 5 and 10 mM) and/or 5 uM of DDP. Flow cytometry was
performed to examine cell apoptosis, and western blotting was used to measure the
expression of extracellular signal-related kinase 1/2 (ERK1/2) phosphorylated (p)
ERK1/2, vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), B
cell lymphoma 2 (Bcl-2), Bcl-2-associated X (Bax) and caspase-3. The resultsof
the present study revealed that metformin reduced the viability of HO-8910 cells
in a time- and concentration-dependent manner and induced cell apoptosis in a
concentration-dependent manner. Metformin combined with DDP evidently inhibited
cell viability and induced apoptosis. In addition, ERK1/2 and genes associated
with apoptosis regulation, such as VEGF, VEGFR2, Bcl-2, Bax and caspase-3,
exhibited differential expression in the HO-8910 cells. The present study
demonstrated that expression of p-ERK1/2, VEGF, VEGFR2 and Bcl-2 was
downregulated by treatment with increasing concentrations of metformin, whereas
expression of Bax and caspase-3 was evidently upregulated. Taken together, these
data demonstrate that metformin in combination with DDP reduces cell viability
and induces apoptosis of human ovarian cancer cells.
PMID- 29344203
TI - Mucin 1 promotes radioresistance in hepatocellular carcinoma cells through
activation of JAK2/STAT3 signaling.
AB - Mucin 1 (MUC1) is aberrantly overexpressed in numerous human cancer types,
including hepatocellular carcinoma (HCC) and contributes to chemoresistance of
tumor cells. The aim of the present study was to evaluate the possible
implication of MUC1 in radioresistance of HCC cells and the underlying
mechanisms. It was demonstrated that MUC1 was significantly upregulated in HCC
cells following irradiation exposure, which was coupled with increased
phosphorylation of signal transducer and activator of transcription 3 (STAT3).
Enforced expression of MUC1 significantly (P<0.05) promoted the clonogenic
survival of HCC cells following irradiation compared with empty vector
transfected cells. MUC1 overexpression resulted in >60% reduction in apoptosis
induced by irradiation, as determined by Annexin-V/propidium iodide double
staining and flow cytometry analysis. Furthermore, overexpression of MUC1
significantly (P<0.05) attenuated the activation of caspase-3 and poly (ADP
ribose) polymerase in response to irradiation exposure. Mechanistically, MUC1
inhibited irradiation-induced apoptosis through activation of janus kinase 2
(JAK2) and STAT3, and induction of anti-apoptotic proteins induced myeloid
leukemia cell differentiation protein Mcl-1 (Mcl-1) and BCL2 like 1 (Bcl-xL).
Small hairpin RNA-mediated knockdown of STAT3 or MUC1 resensitized MUC1
overexpressing cells to irradiation-induced apoptosis, which was accompanied by
reduced expression of Bcl-xL and Mcl-1. Collectively, MUC1 contributes to
radioresistance of HCC cells likely through activation of the JAK2/STAT3
signaling pathway and thus represents a potential target for improving
radiotherapy against HCC.
PMID- 29344204
TI - Silibinin inhibits the migration and invasion of human gastric cancer SGC7901
cells by downregulating MMP-2 and MMP-9 expression via the p38MAPK signaling
pathway.
AB - The objective of the present study was to observe the effects of silibinin and
the p38 mitogen-activated protein kinase (MAPK) signaling pathway inhibitor
SB203580 on the migration and invasion capabilities of SGC7901 cells, and to
explore the underlying associated mechanisms. Scratch, Transwell and Matrigel
invasion assays were performed to study the effects of silibinin on cell
migration and invasion. Western blot analysis was used to determine the
expression levels of p38MAPK, phosphorylated (p-)p38MAPK, matrix
metalloproteinase (MMP)-2 and MMP-9. At the genomic level, quantitative
polymerase chain reaction was performed to evaluate the expression levels of MMP
2 and MMP-9. The results of scratch assay indicated that silibinin inhibited the
migration capabilities of human gastric cancer SGC7901 cells in a dose-dependent
manner. Additionally, Matrigel invasion and Transwell migration assays revealed
that silibinin and SB203580 combined treatment significantly reduced the number
of invasive cells. Western blot analysis indicated a reduced phosphorylation of
p38MAPK without marked changes in p38MAPK expression. In addition, the expression
of MMP-2 and MMP-9 significantly decreased in the presence of silibinin,
SB203580, and the combination of silibinin and SB203580. In summary, silibinin
decreased the invasion and migration abilities of SGC7901 cells by downregulating
the expression of MMP-2 and MMP-9 through inhibiting p38MAPK signaling cascades.
PMID- 29344205
TI - MicroRNA-138 suppresses cell proliferation and invasion of renal cell carcinoma
by directly targeting SOX9.
AB - An accumulating number of studies have reported that the expression levels of
microRNAs (miRNAs/miRs) are dysregulated in a variety of human cancer types,
including renal cell carcinoma (RCC). miRNAs play essential functions in
tumorigenesis and the progression of tumors by serving as oncogenes or tumor
suppressors. Recently, the expression and functions of miR-138 have been studied
in a number of human cancer types; however, its role in RCC remains poorly
understood. In the present study, the results revealed that miR-138 was
significantly downregulated in RCC cell lines and tissues, and that low
expression levels of miR-138 were correlated with histological grade, tumor stage
and lymph node metastasis. In functional studies, restoration of miR-138
expression inhibited cell proliferation and invasion of ACHN and A498 cells. In
addition, SOX9 was validated as a direct target gene of miR-138 in RCC. SOX9
knockdown inhibited cell proliferation and invasion of RCC, with a similar effect
to that induced by miR-138, rendering SOX9 a functional target of miR-138 in the
disease. These findings indicate that miR-138 may present a novel target for
therapeutic strategies in RCC.
PMID- 29344206
TI - Impact of metastatic status on the prognosis of EGFR mutation-positive non-small
cell lung cancer patients treated with first-generation EGFR-tyrosine kinase
inhibitors.
AB - The aim of the present study was to analyze the impact of metastatic status on
the prognosis of epithelial growth factor receptor (EGFR) mutation-positive
patients with non-small cell lung cancer (NSCLC) treated with first-generation
EGFR-tyrosine kinase inhibitors (TKIs). A total of 178 EGFR mutation-positive
patients with stage IIIB-IV and relapsed NSCLC who were treated with gefitinib or
erlotinib as the first-line treatment were enrolled in the present study.
Metastatic status, progression-free survival (PFS), overall survival (OS) and
treatment-response rates were investigated. The association between the number of
metastatic organ sites and patient prognosis was also investigated. The median
age at the time of treatment was 72 (range, 39-91) years. A total of 168 patients
had adenocarcinoma; 156 were treated with gefitinib. Patients with brain
metastases, bone metastases, liver metastases and pleural effusion exhibited a
significantly reduced PFS and OS time in the univariate analysis, compared with
patients without each of these symptoms. In the multivariate analysis, bone
metastasis was associated with a poorer PFS (hazard ratio, 2.11; 95% confidence
interval, 1.44-3.09; P<0.001) and brain metastasis was associated with a poorer
OS (hazard ratio, 2.41; 95% confidence interval, 1.46-3.95; P<0.001). No
association was observed between metastatic status and treatment response rates.
Higher numbers of different sites of organ metastases were associated with
significantly poorer PFS and OS. Bone, brain metastasis and higher numbers of
metastatic organ sites are negative prognostic factors for EGFR mutation-positive
NSCLC patients treated with first-generation EGFR-TKIs.
PMID- 29344207
TI - Novel homobarringtonie-containing therapy for the treatment of patients with
primary acute myeloid leukemia that are resistant to conventional therapy.
AB - The current study investigated the efficacy and safety of a novel treatment
regime consisting of homobarringtonie, cytosine arabinoside and etoposide (HCE)
for the treatment of primary acute myeloid leukemia (AML). In the present study,
141 patients diagnosed with AML were divided into the HCE (n=47) and the
conventional AML therapy, consisting of idamycin combined with cytarabine (IA;
n=94), treatment groups. The measured patient outcome parameters were the
emission and response rates, as well as medication-induced adverse events, with a
median follow-up time of 28 months. There was no significant difference in the 3
year relapse-free survival rate between the HCE and IA treatment groups. The
occurrence and severity of hematological or non-hematological toxicity did not
differ between the two groups. However, of the 26 patients that demonstrated a
poor response to the IA treatment, 19 cases were administered the HCE treatment
and 14 of these patients achieved complete remission (CR). Of the 10 patients
that demonstrated a poor response to the HCE treatment, 8 patients were
administered the IA treatment and 7 of these achieved CR. Therefore, HCE may be
an effective treatment regimen for patients with primary AML. As there was no
cross-resistance between the HCE and IA regimens, HCE may be an alternative
option for patients that respond poorly to IA induction therapy.
PMID- 29344208
TI - Serum levels of anti-sperm-associated antigen 9 antibody are elevated in patients
with hepatocellular carcinoma.
AB - At present, there is a high incidence of viral hepatitis and high mortality rates
due to hepatocellular carcinoma (HCC) in China. In the current study, the
quantification of antibodies against the cancer-testis antigen sperm-associated
antigen 9 (SPAG9), alone and combined with alpha-fetoprotein (AFP), were
evaluated as biomarkers for the diagnosis of HCC. The levels of anti-SPAG9
antibody and AFP were quantified in serum samples from patients with HCC and
hepatitis or cirrhosis, as well as healthy volunteers. The results revealed that
the serum levels of anti-SPAG9 immunoglobulin G antibody in patients with HCC
were significantly higher compared with those in patients with
hepatitis/cirrhosis and healthy controls. Using receiver operator characteristic
curves, the area under the curve (AUC, 0.870) of SPAG9 as a diagnostic marker of
HCC was significant [P<0.001; 95% confidence interval (CI), 0.793-0.947], whereas
the AUC of AFP was 0.832 (P<0.001; 95% CI, 0.736-0.928). Serum anti-SPAG9
antibody levels exhibited significant potential for the differential diagnosis of
HCC, with an AUC value of 0.729, (P=0.008; 95% CI, 0.559-0.899). Similarly, serum
AFP levels exhibited significant value for the differential diagnosis of HCC,
with an AUC value of 0.842 (P<0.001; 95% CI, 0.732-0.953). When combined with
quantification of AFP, the diagnostic sensitivity and specificity of anti-SPAG9
levels were increased. In summary, the results suggested that anti-SPAG9 antibody
is a potential early diagnostic marker of HCC.
PMID- 29344209
TI - The effect of royal jelly on the growth of breast cancer in mice.
AB - Due to various pharmacological properties, including antioxidative, anti
inflammatory and antibiotic properties, royal jelly (RJ) has been widely consumed
in daily diets in numerous countries. In the present study, the effect of RJ on
4T1-bearing mice was investigated. The study was performed by feeding 4T1-bearing
mice with RJ using either the prophylactic-therapeutic (PTRJ) or therapeutic
(TRJ) method. The experimental results for the PTRJ group demonstrated that the
weight of tumor was significantly reduced (RJ 0.5 and 1.5 g/kg); and in the
serum, the levels of interleukin (IL)-2 (RJ 0.5 and 1.5 g/kg), interferon (IFN)
alpha, superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) were
significantly elevated, but the concentrations of IL-4 (RJ 0.5 and 1.5 g/kg) and
IL-10 (RJ 1.0 g/kg) were significantly decreased. In addition, the activities of
T-AOC and glutathione reductase (GR) were significantly improved in the liver,
whereas in the kidney, the activities of T-AOC and GR were significantly
increased only under the dose of 0.5 g/kg. For the TRJ group, the antitumor
effect of RJ was not significant; the change in IL-2, IFN-alpha, SOD and T-AOC
levels in the serum, and the change in T-AOC and GR in liver were similar to
those observed in the PTRJ groups. RJ treatment was demonstrated to reduce the
development of breast tumor in mice, and simultaneously improve the antioxidant
capacity of the serum, liver and kidney, particularly using the prophylactic
therapeutic method. These results corroborated the efficacy of RJ supplementation
in diets. The results of the present study suggest that the antioxidant and
immunomodulatory activities of RJ serve an important role on antitumor growth.
PMID- 29344210
TI - MicroRNA-335 is downregulated in papillary thyroid cancer and suppresses cancer
cell growth, migration and invasion by directly targeting ZEB2.
AB - MicroRNAs (miRs) are a group of short, endogenous, non-protein-coding and single
stranded RNAs that regulate gene expression by binding to the 3'-untranslated
region (3'UTR) of mRNAs, which results in their degradation or translational
repression. The aim of the present study was to investigate the expression and
function of miR-335 in human papillary thyroid cancer (PTC). Reverse
transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to
quantify the relative miR-335 expression levels in PTC tissues and cell lines.
The effect of miR-335 on the proliferation, migration and invasion of PTC cells
was assessed by an MTT assay, and transwell migration and invasion assays,
respectively. Dual-luciferase reporter assays were employed to explore whether
miR-335 directly targeted the 3'UTR of the potential target gene zinc finger E
box binding homeobox 2 (ZEB2). RT-qPCR and western blotting were adopted to
assess the effect of miR-335 on the mRNA and protein expression of ZEB2. RT-qPCR
revealed that miR-335 was downregulated in PTC tissues and cell lines. The MTT
assay and transwell migration and invasion assays demonstrated that the
overexpression of miR-335 significantly inhibited the proliferation, migration
and invasion of PTC cells. ZEB2 was identified as a direct target of miR-335 with
computational analysis, which was confirmed with a dual-luciferase reporter
assay, RT-qPCR and western blotting. The knockdown of ZEB2 significantly
inhibited the proliferation, migration and invasion of PTC cells, indicating that
ZEB2 may be a functional target of miR-335. Taken together, these findings
suggested that miR-335 functioned as a tumor suppressor and suppressed the growth
and metastatic behavior of PTC cells by targeting ZEB2.
PMID- 29344211
TI - Prevalence of HPV infection among HIV-positive and HIV-negative women in
Central/Eastern Italy: Strategies of prevention.
AB - The present cross-sectional-study aimed to determine the prevalence of human
papillomavirus (HPV)-genotypes among human immunodeficiency virus (HIV)-positive
and -negative women in Central/Eastern Italy, and to identify the optimal
strategies for effective HPV-prevention in each group. A representative sample of
HIV-negative (150/200) and -positive (50/200) women, who underwent cervico
vaginal-swabbing. Swabs were analysed for a cytological screening and for a HPV
DNA-genotyping-test. A total of 66/200 swabs resulted HPV-positive. The overall
HPV-prevalence was 33% with a higher prevalence in the HIV-positive-group (48%)
compared with the HIV-negative-group (28%). The most frequent genotypes were: 16,
31, 52, 58, 66, 73 and 89. Furthermore, the prevalence of specific genotypes was
different in each group. The results of the present study indicate that HIV
infection appears to be an independent risk factor for HPV-infection. In
addition, HPV-infection is more common and more likely to persist in HIV-positive
compared with in HIV-negative women. The optimal way to counteract HPV infection
is through primary prevention. The stage of immunity (cluster of differentiation
4-level) at the time of the HPV-screening is one of the most important parameters
for detection of susceptibility to HPV-infection and to evaluate the response to
the HPV-vaccine in HIV-positive women. It may be used to determine the sub-group
of HIV-positive women that are more prone to HPV-infections or that exhibit a
partial response to the HPV-vaccine. At present, a novel type of vaccine with 9
genotypes is available and in the near future, it may serve an essential role in
the prevention of HPV infections.
PMID- 29344212
TI - Coexistence of sarcoidosis and metastatic lesions: A diagnostic and therapeutic
dilemma.
AB - Sarcoidosis, a chronic, inflammatory disease that affects various different
organs, is characterized by noncaseating epitheloid granulomas. This systemic
inflammatory process is associated with an increased risk of cancer. Several
cases of sarcoidosis that mimic metastatic tumor progression in radiological
findings have been reported so far. However, there are also cases that have
presented a coexistence of sarcoidosis and metastasis, which have caused a
diagnostic and therapeutic dilemma. Due to inadequate current therapies, a
reliable differentiation between benign and malignant lesions is crucial. This
review focuses on the residual risk of the coexistence of metastases within
radiological suspicious lesions in patients with a history of solid tumors and
sarcoidosis, as well as immunological findings, in order to explain the potential
associations. Sarcoidosis has the potential to promote metastasis as it includes
tumor-promoting and immune-regulating cell subsets. Notably, myeloid derived
suppressor cells may serve a pivotal role in metastatic progression in patients
with sarcoidosis. In addition, the present review also evaluates the potential
novel diagnostic approaches, which may be able to differentiate between
metastatic lesions and sarcoidosis. The risk of coexistent metastasis in
sarcoidosis lesions must be considered by clinical practitioners, and a
multidisciplinary approach may be required to avoid misdiagnosis and the
subsequent unnecessary surgery or insufficient treatments.
PMID- 29344214
TI - Association of the rs2071559 (T/C) polymorphism with lymphatic metastasis in
patients with nasopharyngeal carcinoma.
AB - Vascular endothelial growth factor (VEGF) and its receptor, VEGFR2, serve a
critical role in angiogenesis and lymphangiogenesis, which are involved in the
initiation and progression of malignancies. Specific single nucleotide
polymorphisms of VEGF and VEGFR2 have been shown to modulate gene expression and
influence malignancy aggressiveness. The aim of the present study was to
determine whether the VEGFR2 rs2071559 (T/C) polymorphism is associated with the
risk of developing nasopharyngeal carcinoma (NPC) and the aggressiveness of NPC
in a southern Chinese population. A case-control study comprising 171 NPC
patients and 184 healthy individuals was performed. Genotyping of the rs2071559
polymorphism was performed by quantitative polymerase chain reaction using TaqMan
probes. Genotype and allele distribution of the rs2071559 polymorphism was not
associated with the risk of NPC following adjustment for age, sex and ethnicity
by multivariate logistic regression analyses. Regional lymph node metastasis was
significantly correlated with the rs2071559 C allele and the related genotypes
(OR 0.402, 95% CI 0.193-0.835, P=0.016; and OR 0.347, 95% CI 0.145-0.829,
P=0.024, respectively). No correlations between genotype or allele distribution
and the primary tumor size, distant metastasis, clinical stage, or histological
type were observed. The rs2071559 polymorphism was shown to have an association
with lymphatic metastasis in patients with NPC; however, the precise molecular
mechanism should be elucidated in additional studies.
PMID- 29344213
TI - Sentinel lymph node mapping in gynecological oncology.
AB - The intraoperative mapping of sentinel lymph nodes (SLNs) is part of the
treatment strategy for a number of types of tumor. To retrospectively compare
results from the mapping of pelvic SLNs for gynecological oncology, using
distinct dyes, the present review was conducted to determine the clinical
significance of SLN mapping for gynecological oncology. In addition, the present
study aimed at identifying an improved choice for SLN mapping tracers in clinical
application. Each dye exhibits demerits when applied in the clinical environment.
The combination of radioisotopes and blue dyes was identified to exhibit the most
accurate detection rate of SLN drainage of gynecological oncology. However,
contrast agents were unable to identify whether a SLN is positive or negative for
metastasis prior to pathologic examination; additional studies are required.
PMID- 29344215
TI - miR-203a suppresses cell proliferation by targeting E2F transcription factor 3 in
human gastric cancer.
AB - MicroRNAs (miRs) are a class of short non-coding RNAs that serve an essential
role in the tumorigenesis of gastric cancer (GC). MiR-203a has been reported as a
tumor repressor in various types of human cancer. In the present study, the
function of miR-203a on the proliferation of GC cells was investigated.
Bioinformatics analyses revealed that miR-203a targets the 3'-untranslated region
of E2F transcription factor 3 (E2F3) messenger RNA. A luciferase reporter assay
and western blot analysis were performed to confirm whether E2F3 was a target of
miR-203a. The relative luciferase activity was decreased when overexpressing miR
203a with E2F3-wild type pmirGLO-3'-untranslated region vector, compared with the
control group in HEK293 cells. Overexpression of miR-203a suppressed cell
proliferation and colony formation of SGC-7901 and AGS GC cells. Inhibition of
miR-203a promoted the proliferation of GC cells. Collectively, the results
indicated that miR-203a may function as a tumor suppressor in GC by targeting
E2F3.
PMID- 29344216
TI - Hypermethylation downregulates P2X7 receptor expression in astrocytoma.
AB - The present study investigated the altered expression of p2X purinoceptor (P2X7R)
in astrocytoma. Reverse transcription-quantitative polymerase chain reaction and
western blot analysis were used to determine the P2X7R expression in glioblastoma
(GBM) and surrounding normal brain tissue. DNA methylation levels of P2X7R gene
promoter in GBM were analyzed using a Sequenom MassARRAY(r) System.
Immunohistochemistry (IHC) was used to detect the expression of P2X7R in
astrocytoma at different malignancy grades, including diffuse astrocytoma,
anaplastic astrocytoma and GBM. P2X7R mRNA and protein were significantly
decreased in GBM compared with normal brain tissues. IHC results showed a
negative correlation between P2X7R expression and tumor grade. The decreased
P2X7R expression was mostly attributed to hypermethylation of its promoter.
Therefore, P2X7R was found to perform an important role in tumorigenesis and
progression of astrocytoma.
PMID- 29344217
TI - Aleukemic extramedullary T lymphoid/myeloid bilineage hematopoietic and lymphoid
malignancy with progression to bilineage leukemia at relapse: A case report.
AB - Bilineage T lymphoid and myeloid (T/My) neoplasms are rare entities among the
hematopoietic and lymphoid malignancies. The majority of patients present with
leukemic symptoms in which blasts are observed in the peripheral blood (PB) or
bone marrow (BM) at a percentage of >20% of nucleated cells. Only a minimal
number of cases of T/My bilineage hematopoietic and lymphoid malignancy have been
reported with extramedullary infiltration as the initial symptom. The origin of
the neoplastic cells in T/My bilineage malignancy has been documented as the
hematopoietic stem cells. The present study reports the case of a 31-year-old man
with a T/My bilineage malignancy, which initially showed cervical lymph node
enlargement beyond the diagnostic criteria of leukemia in the PB and in the BM.
Two distinct malignant populations were detected in the cervical lymph node and
pleural effusion, one of which was positive for MPO-staining, while the other was
positive for cytoplasmic cluster of differentiation 3. Mutations in platelet
derived growth factor receptor alpha, platelet-derived growth factor receptor
beta, fibroblast growth factor receptor 1 and other chromosome abnormalities were
excluded. The patient obtained complete remission after conventional
chemotherapy, but relapsed with bilineage leukemia within a short period of time.
Lymphoid and myeloid lineages have been reported to be differentiated from
multipotent progenitors asymmetrically. However, the cellular mutation stage in
T/My bilineage malignancy remains unclear. The present study also reviews the
origin, development and therapeutic strategies for extramedullary T/My bilineage
malignancy.
PMID- 29344218
TI - ATRA increases iodine uptake and inhibits the proliferation and invasiveness of
human anaplastic thyroid carcinoma SW1736 cells: Involvement of beta-catenin
phosphorylation inhibition.
AB - All-trans-retinoic acid (ATRA) can enhance iodine uptake capability of thyroid
tumors, but the mechanisms remain poorly understood. The aim of the present study
was to investigate the effects of ATRA on isotope susceptibility, proliferation
and invasion of anaplastic thyroid carcinoma (ATC) and potential mechanisms.
SW1736 cells were treated with 1 umol/l ATRA or 1% ethanol for 5 days. A cell
line stably expressing beta-catenin-shRNA was established. An iodine uptake assay
was performed using 125I. Proliferation and invasiveness were tested using MTT
and Transwell assays, respectively. Western blotting was used to assess the
expression of beta-catenin, glycogen synthase kinase-3beta (GSK-3beta),
sodium/iodine symporter (NIS) and proteins involved in epithelial-mesenchymal
transition. Cells pretreated with ATRA were injected subcutaneously into SCID
mice. Mice were intraperitoneally injected with 131I once on the first day of
treatment, and tumor growth was then assessed. After 35 days of 131I treatment,
ATRA-pretreated tumor volume and weight were decreased compared with the 131I
alone group (163.32+/-19.57 vs. 332.06+/-21.37 mm3; 0.35+/-0.14 vs. 0.67+/-0.23
g, both P<0.05). Similar results were observed in the beta-catenin shRNA
pretreated tumors. ATRA also increased the uptake of iodine by SW1736 cells
(P<0.01), and similar results were observed in beta-catenin shRNA cells. ATRA
treatment decreased the cell proliferation and invasion compared with control
cells (all P<0.05), similar to beta-catenin shRNA. ATRA treatment decreased the
expression of phosphorylated (p-)beta-catenin, p-GSK-3beta, vimentin, and
fibronectin, and increased the expression of NIS and E-cadherin, compared with
the control. ATRA increased the iodine uptake and inhibited the proliferation and
invasion of SW1736 cells, involving beta-catenin phosphorylation. In conclusion,
ATRA could be used to improve the isotope sensitivity of ATC.
PMID- 29344219
TI - Upregulation of miR-146a increases cisplatin sensitivity of the non-small cell
lung cancer A549 cell line by targeting JNK-2.
AB - The aim of the present study was to investigate the effects of microRNA (miR
)146a on the cisplatin sensitivity of the non-small cell lung cancer (NSCLC) A549
cell line and study the underlying molecular mechanism. The differences in
expression of miRNAs between A549 and A549/cisplatin (A549/DDP) cells were
determined, and miR-146a was selected to study its effect on cisplatin
sensitivity of A549/DDP cells. miR-146a mimic and inhibitor transient
transfection systems were constructed using vectors, and A549/DDP cells were
infected with miR-146a mimic and inhibitor to investigate growth, apoptosis and
migration. The directed target of miR-146a was determined and the underlying
molecular mechanism was validated in the present study. The results of the
present study demonstrated that miR-146a was downregulated in NSCLC A549/DDP
cells, compared with A549 cells. The overexpression of miR-146a induced apoptosis
and inhibited the growth and invasion of A549/DDP cells, which resulted in
increased cisplatin sensitivity in NSCLC cells. The JNK2 gene was determined as
the direct target of miR-146a, and may be activated by the overexpression of miR
146a. Additionally, JNK2 activated the expression of p53 and inhibited B cell
lymphoma 2. The upregulation of miR-146a increased cisplatin sensitivity of the
A549 cell line by targeting JNK2, which may provide a novel method for treating
NSCLC cisplatin resistance.
PMID- 29344220
TI - Overexpression of microRNA-1470 promotes proliferation and migration, and
inhibits senescence of esophageal squamous carcinoma cells.
AB - MicroRNA-1470 (miR-1470) is overexpressed in esophageal squamous cell carcinoma
(ESCC); however, its role and underlying molecular mechanism remain unknown. The
aim of the present study was to explore the tumorigenic role and mechanism of miR
1470 overexpression in ESCC. The expression of miR-1470 in ESCC tissues and cell
lines was detected using human miRNA microarrays and the reverse transcription
quantitative polymerase chain reaction, respectively. The effects of miR-1470 on
cell proliferation, migration and senescence were determined using a Cell
Counting Kit-8 assay, Transwell migration assay and beta-galactosidase staining
kit. Western blotting was used to analyze the expression levels of genes in the
apoptosis signaling pathway. An increased expression level of miR-1470 was
observed in ESCC tissues compared with that in paracancerous tissues. Knockdown
of miR-1470 significantly suppressed proliferation, and down-regulated the cell
cycle regulatory gene cyclin E1. It was also revealed that knockdown of miR-1470
significantly inhibited migration, and decreased the expression levels of matrix
metalloproteinase 2 (MMP2), MMP13 and MMP14. Western blotting analysis revealed
that knockdown of miR-1470 induced apoptosis by increasing B-cell lymphoma 2 (Bcl
2) expression. The results of the present study suggest that overexpression of
miR-1470 in ESCC promotes cancer cell proliferation by accelerating the cell
cycle and inhibiting apoptosis, and also enhances cancer cell migration by
upregulating MMPs.
PMID- 29344221
TI - Livin serves as a prognostic marker for mid-distal rectal cancer and a target of
mid-distal rectal cancer treatment.
AB - Livin is a novel member of the inhibitor of apoptosis protein family, which has
been identified to be expressed in various malignancies and is suggested to be
associated with poor prognostic significance. However, no data are available
concerning the significance of livin in mid-distal rectal cancer. In the present
study, livin expression, and its association with clinicopathological
characteristics and prognosis was examined in patients with mid-distal rectal
cancer. Apoptotic susceptibility, invasion capacity and chemosensitivity of LoVo
cells were investigated using small interfering RNA (siRNA)-mediated knockdown of
livin. It was revealed that livin was highly expressed in mid-distal rectal
cancer tissues compared with the normal rectal mucosal tissues. Livin expression
was associated with pathological grade, extent of invasion (T stage) and extent
of lymph node metastasis (N stage) of tumor, contributing to poor prognosis of
mid-distal rectal cancer following surgery. The data suggest that aggressive
surgery should be applied in patients with mid-distal rectal cancer with high
expression of livin. It was also revealed that knockdown of livin by siRNA
increased the apoptotic rate, suppressed invasion of LoVo cells, and decreased
the half-maximal inhibitory concentration of oxaliplatin and 5-fluorouracil by
~50% in LoVo cells significantly compared with control groups. The data suggested
that a combination of downregulation of livin and anticancer drugs may
significantly decrease the toxicity of anticancer drugs. Taken together, the
present study indicated that livin may be a promising target in clinical therapy
of mid-distal rectal cancer.
PMID- 29344222
TI - Herbal compound Teng-Long-Bu-Zhong-Tang inhibits metastasis in human RKO colon
carcinoma.
AB - Metastasis is one of the primary obstacles to the successful treatment of
colorectal cancer. Teng-Long-Bu-Zhong-Tang (TLBZT) is a modern Chinese herbal
formula that may be useful in the treatment of metastatic colorectal cancer. The
present study evaluated the effects of TLBZT on lung metastasis in human RKO
colon carcinoma cells injected into mice via the tail vein. The results
demonstrated that TLBZT inhibited the metastasis of human RKO colon carcinoma
cells to the lungs. TLBZT downregulated the expression of LOX and hypoxia
inducible factor 1alpha. TLBZT also inhibited the expression of integrins alphaV
and beta3 and the phosphorylation of focal adhesion kinase. These results
indicate that TLBZT inhibits the lung metastasis of RKO colon carcinoma by
regulating the expression of multiple genes. The results of the present study
provide a new basis for the management of colorectal cancer metastasis using
treatments derived from Chinese herbs.
PMID- 29344223
TI - Application of intensity-modulated radiation therapy in the treatment of
nasopharyngeal carcinoma.
AB - The objective of the present study was to investigate the application values of
the intensity-modulated radiation therapy (IMRT) and the three-dimensional
conformal radiation therapy (3D-CRT) in the treatment of nasopharyngeal carcinoma
(NPC). A total of 124 patients diagnosed with nasopharyngeal carcinomas were
included into the study and randomly divided into the control group and the
observation group, with 62 patients in each group. The 3D-CRT combined with
postoperative chemotherapy were performed on the control group and the
observation group received IMRT combined with postoperative chemotherapy, and
then were followed up for a median duration of 25.5 months. Comparison of the
survival analysis of the two groups showed no differences between them in terms
of the total effective rate and effectiveness (P>0.05), or radiotherapy
complications (P>0.05). In addition, no significant differences between the two
groups were found in the follow-up local tumor control probability (TCP),
regional lymph node control rate, distant metastasis-free rate, tumor-free
survival rate, recurrence rate and overall survival rate (P>0.05). Furthermore,
there was no difference between the two groups in the overall score of quality of
life (P>0.05). The present study concludes that the IMRT and the 3D-CRT have
almost the same short-term and long-term clinical effects in the treatment of
nasopharyngeal carcinoma and both of them have high effectiveness and safety.
PMID- 29344224
TI - Long-term outcomes of microwave endometrial ablation for treatment of patients
with menorrhagia: A retrospective cohort study.
AB - This study aimed to describe the long-term outcomes of patients with menorrhagia
treated with microwave endometrial ablation (frequency, 2.45 GHz), as well as to
identify factors associated with recurrence or re-surgery. This retrospective
cohort study was conducted from 2007 to 2015 at Shimane University Hospital in
Japan. Patients with severe menorrhagia and a desire to preserve their uterus
were included in the study. Clinical factors associated with recurrence of
menorrhagia or re-surgery were analyzed with a multivariable logistic regression
model. Of 160 microwave endometrial ablation candidates, 100 had uterine myomas,
20 adenomyosis, 26 functional excessive menstruation, and 12 endometrial polyps.
In the full cohort, age (<40) and uterine cavity length (>=10) were associated
with recurrence of menorrhagia and re-surgery. Among patients with myomas, age
(<48) and number of myomas (>=4) were associated with recurrence, and largest
myoma size (>=5) and preoperative hemoglobin level (<9 mg/dl) were associated
with re-surgery. Among subjects with adenomyosis, uterine cavity length (>=10)
was associated with recurrence. Microwave endometrial ablation is thought to be a
highly efficacious method to control menorrhagia caused by functional bleeding
and endometrial polyps. However, microwave endometrial ablation may be less
effective for patients younger than 48 years with myomas, especially those with 4
or more myomas, or with a myoma 5 cm or larger in size, and for patients with
adenomyosis who have a thickened myometrium. These clinical factors may be useful
predictors of success in selecting candidates for microwave endometrial ablation.
PMID- 29344225
TI - Metformin enhances the chemosensitivity of hepatocarcinoma cells to cisplatin
through AMPK pathway.
AB - This study investigated the effect of metformin on chemosensitivity of
hepatocarcinoma cells to cisplatin and the possible mechanism. HepG2 and Huh-7
hepatoma cells were treated with cisplatin at concentrations of 0, 2, 4, 6, 8 and
10 uM for 48 h. Proliferation of HepG2 and Huh-7 hepatoma cells were detected by
MTT assay. Apoptosis of hepatocellular carcinoma cells was detected by flow
cytometry. Western blot analysis was used to detect the expression of 5
monophosphate-activated protein kinase (AMPK) and p-AMPK protein. Proliferative
activity of HepG2 and Huh-7 cells decreased with the increase of cisplatin
concentration. After adding metformin, proliferation ability of hepatocarcinoma
cells was significantly reduced. Apoptosis rate of the metformin was
significantly higher than that of the control group, and apoptosis rate of the
cisplatin + metformin was significantly higher than that of the cisplatin group.
There was no significant difference in expression level of AMPK protein found
between control, metformin, cisplatin and cisplatin + metformin group. Compared
with the control, ratio of p-AMPK/AMPK in metformin group was increased, and
ratio of p-AMPK/AMPK in cisplatin + metformin was significantly higher than that
in cisplatin group. Activity of cells in cisplatin + metformin + compound C (AMPK
pathway blocker) group was significantly higher than that of cisplatin +
metformin, while apoptosis of cells in cisplatin + metformin + compound C (AMPK
pathway blocker) was significantly lower than that of cisplatin + metformin
group. In conclusion, metformin can inhibit the proliferation, promote apoptosis
and enhance the chemosensitivity of hepatocarcinoma cells to cisplatin through
AMPK pathway.
PMID- 29344226
TI - Analysis of survival and prognosis of 298 gastric adenocarcinoma patients with no
distant metastasis.
AB - This study investigated the survival and prognosis of 298 gastric adenocarcinoma
patients with no distant metastasis. For analysis and comparison of the prognosis
of patients, a retrospective analysis was performed in 298 patients with perfect
clinical data and follow-up data who received the D2 resections for gastric
cancer in Shandong Provincial Hospital Affiliated to Shandong University between
January, 2005 and January, 2012, and were diagnosed as gastric adenocarcinoma
with no distant metastasis in postoperative pathological examination. Among the
gastric adenocarcinoma patients without distant metastasis, we found that
differences of sex, age, differentiation and position of tumor had no statistical
significance (P>0.05), while comparisons of the tumor diameter, regional
lymphatic metastasis, vascular invasion and pathological TNM stages (pTNM; T for
tumor, N for lymph node and M for metastasis) showed statistical significance
(P<0.05). One-way analysis of variance (ANOVA) indicated the correlation between
the prognosis of gastric adenocarcinoma patients and tumor diameter, regional
lymphatic metastasis, vascular invasion and pTNM stages of patients (P<0.05).
Multivariate analysis of Cox regression models was performed for discovering the
factors associated with the prognosis of patients, and the results suggested that
position of tumor (P=0.016), regional lymphatic metastasis (P=0.042), vascular
invasion (P=0.021) and pTNM stage (P=0.009) were the independent risk factors
affecting the prognosis of gastric adenocarcinoma patients. During 60-month
follow-up, the median survival duration of gastric adenocarcinoma patients with
no distant metastasis was 38 months, while the 5-year accumulate survival rate
was 49.3%. The results indicated that in gastric adenocarcinoma patients without
distant metastasis, tumor diameter, regional lymphatic metastasis, vascular
invasion and pTNM stage are major indicators affecting the prognosis of patients.
PMID- 29344227
TI - Sirolimus treatment for cirrhosis or hepatocellular carcinoma patients
accompanied by psoriasis after liver transplantation: A single center experience.
AB - There is currently no consensus on the most suitable therapeutic approach for
psoriasis (PS) co-existing with posthepatic cirrhosis (PCs) and hepatocellular
carcinoma (HCC) following liver transplantation (LT). The present study provides
an analysis of the therapeutic experience of such patients. Five LT recipients
(two with PC and three with HCC) with accompanying PS were included. The
induction program consisted of methylprednisolone plus basiliximab treatment. The
initial postoperative treatment scheme consisted of tacrolimus (FK506) plus
mycophenolate mofetil (MMF) and hormone; the latter was withdrawn 1 week after
LT. The patients with PC had been using FK506 with or without a postoperative MMF
program; the patients with HCC and recurrence of PS had been switched to a
sirolimus (SRL)-based replacement therapy. Furthermore, all patients received
anti-hepatitis B virus (HBV) therapy. The patients were followed up after 8.3+/
1.5 years. There was a positive correlation between HBV-DNA copy numbers, and
psoriatic area and severity index (PASI) scores (r=0.97; P=0.006). The PASI
scores were decreased significantly at 6 months following surgery compared with
pre-transplantation (P<0.05). The patients who had received the FK506-based
treatment experienced PS recurrence two years post-transplantation. The PASI
scores increased significantly (P<0.05) and then declined gradually, maintaining
a stable level (P<0.05) by 1 year after switching to the SRL-based treatment. The
patients who had received the SRL-based treatment exhibited no recurrence of PS.
The results of the present study suggest that SRL therapy provides a promising
novel treatment method for patients with PS following LT that may be superior to
tacrolimus treatment. When co-existing HBV is present pre-transplantation,
regular injection of human hepatitis B immunoglobulin should be used to prevent
the HBV from relapsing or aggravating the PS.
PMID- 29344228
TI - Expression and clinical significance of ATM and PUMA gene in patients with
colorectal cancer.
AB - The expression of ataxia-telangiectasia mutated (ATM) and p53 upregulated
modulator of apoptosis (PUMA) genes in patients with colorectal cancer were
investigated, to explore the correlation between the expression of ATM and PUMA
and tumor development, to evaluate the clinical significance of ATM and PUMA in
the treatment of colorectal cancer. Quantitative real-time PCR was used to detect
the expression of ATM and PUMA in tumor tissue and adjacent healthy tissue of 67
patients with colorectal cancer and in normal colorectal tissue of 33 patients
with colorectal polyps at mRNA level. The expression level of ATM mRNA in
colorectal cancer tissues was significantly higher than that in normal mucosa
tissues and adjacent non-cancerous tissue (P<=0.05), while no significant
differences in expression level of ATM mRNA were found between normal mucosa
tissues and adjacent noncancerous tissue (P=0.07). There was a negative
correlation between the expression of ATM mRNA and the degree of differentiation
of colorectal cancer (r= -0.312, P=0.013), while expression level of ATM mRNA was
not significantly correlated with the age, sex, tumor invasion, lymph node
metastasis or clinical stage (P>0.05). Expression levels of PUMA mRNA in
colorectal cancer tissues, adjacent noncancerous tissue and normal tissues were
0.68+/-0.07, 0.88+/-0.04 and 1.76+/-0.06, respectively. Expression level of PUMA
mRNA in colorectal cancer tissues and adjacent noncancerous tissue was
significantly lower than that in normal colorectal tissues (P<0.05). The results
showed that ATM mRNA is expressed abnormally in colorectal cancer tissues.
Expression of PUMA gene in colorectal carcinoma is downregulated, and is
negatively correlated with the occurrence of cancer.
PMID- 29344229
TI - Preparation and characterization of the Adriamycin-loaded amphiphilic chitosan
nanoparticles and their application in the treatment of liver cancer.
AB - In the present study, two nanoparticles including lactose myristoyl carboxymethyl
chitosan (LMCC) and algal polysaccharide myristoyl carboxymethyl chitosan (AMCC),
were obtained for hepatic-targeted Adriamycin (ADM) drug delivery systems. ADM
was successfully loaded into the LMCC or AMCC nanoparticle by dialysis. The
release function and liver targeting of the nanoparticles was explored, and it
was revealed that ADM release from the nanoparticles was greatest at acidic pH
5.5. ADM-conjugated nanoparticles were readily taken up by HU7 human
hepatocellular carcinoma cells, relative to HT22 mouse hippocampal neuron cells
in vitro. In vivo, ADM-loaded nanoparticles had significant antitumor efficacy
with a 62.7% inhibition rate, followed by ADM and ADM-AMCC (51.2 and 42.5%,
respectively). The tissue distribution study confirmed that ADM-LMCC had an
improved liver delivery efficacy, by comparison with ADM. Furthermore, a series
of safety studies, including hemolysis, acute toxicity and organ toxicity,
revealed that the ADM-loaded LMCC and AMCC nanoparticles had advantages over the
commercially available injectable preparation of Adriamycin hydrochloride, in
terms of low toxicity levels and increased tolerated dose. These results
indicated that LMCC is a promising carrier for injectable ADM nanoparticle and
ADM-conjugated nanoparticles may improve the efficacy of ADM by hepatic
targeting.
PMID- 29344230
TI - Reduced miR-105-1 levels are associated with poor survival of patients with non
small cell lung cancer.
AB - Altered expression of microRNAs (miRNAs or miRs) contributes to lung
carcinogenesis. The present study performed an in silico analysis of
differentially expressed miRNAs in different peripheral blood samples from
patients with various diseases vs. controls using the Gene Expression Omnibus
(GEO) database data, and assessed miR-105-1 expression in 32 normal lung and 142
non-small cell lung cancer (NSCLC) tissue samples using reverse transcription
quantitative polymerase chain reaction. Survival data were calculated using
Kaplan-Meier curves and a log-rank test. The stepwise forward Cox regression
model was performed for univariate and multivariate analyses of independent
predictor of overall survival (OS) of patients. The data on in silico and tissue
microarray analyses of miRNA expression revealed reduced miR-105-1 expression in
different types of human cancer, particularly in NSCLC. The level of miR-105-1
expression was confirmed to be downregulated in NSCLC tissues compared with that
in normal lung tissues. Reduced miR-105-1 expression was associated with larger
tumor size as well as poor OS and disease-free survival (DFS) of patients.
Multivariate survival analysis demonstrated that reduced miR-105-1 expression and
tumor size were independent predictors for OS of NSCLC patients. In conclusion,
reduced miR-105-1 expression in NSCLC tissues is associated with poor OS and DFS
of NSCLC patients.
PMID- 29344231
TI - Expression of Beclin 1 and Bcl-2 in pancreatic neoplasms and its effect on
pancreatic ductal adenocarcinoma prognosis.
AB - Aberrant expression of Beclin 1 and B-cell lymphoma-2 (Bcl-2) has been identified
in a variety of human tumors; however, little information is available for
pancreatic neoplasms. The present study analyzed the expression of Beclin 1 and
Bcl-2 in pancreatic ductal adenocarcinoma (PDAC) and solid pseudopapillary
neoplasm (SPN) of the pancreas, and evaluated their prognostic significance for
PDAC. The present study included 117 PDAC, 43 SPN and 32 chronic pancreatitis
(CP) cases. Levels of Beclin 1 and Bcl-2 expression were evaluated
semiquantitatively by immunohistochemistry, and their correlation with the
survival of patients with PDAC was determined. Beclin 1 was upregulated in 74
(63.2%) PDAC, 26 (60.5%) SPN, and 14 (43.8%) CP cases. Bcl-2 was upregulated in
38 (32.5%) PDAC, 11 (25.6%) SPN and 24 (75.0%) CP cases. High Beclin 1 and low
Bcl-2 expression was significantly correlated with poor differentiation and
distant metastasis in PDAC, and associated with the presence of nuclear
pleomorphism in SPN and with advanced Tumor-Node-Metastasis stage in PDAC. Beclin
1 and Bcl-2 levels were inversely correlated in PDAC, whereas they were
positively correlated in SPN. Low Beclin 1 and high Bcl-2 expression was
associated with improved disease-free survival and overall survival (OS).
However, the association of Beclin 1 with survival was not significant in the Cox
analysis, whereas Bcl-2 expression was significantly correlated with OS in the
multivariate analysis. In conclusion, Beclin 1 upregulation exacerbated the
progression and aggressiveness of pancreatic neoplasms, and Bcl-2 downregulated
expression was an independently poor prognostic factor for PDAC.
PMID- 29344232
TI - Novel combination of paraspinal keyhole surgery with a tubular retractor system
leads to significant improvements in lumbar intraspinal extramedullary
schwannomas.
AB - The aim of the present study was to investigate the efficacy of combining
paraspinal keyhole surgery with a tubular retractor system for the microsurgical
removal of lumbar intraspinal extramedullary schwannomas. A retrospective
analysis was conducted of 56 patients with lumbar intraspinal extramedullary
schwannomas who were treated using the microsurgical paraspinal keyhole approach
with a tubular retractor system. The mean +/- standard deviation was calculated
for the following parameters: Surgery time (96.21+/-14.64 min), hemorrhagic
volume (28.54+/-9.72 ml), bed rest (2.55+/-0.5 days) and hospital stay (5.68+/
0.72 days). Two patients presented with cerebrospinal fluid leakage and one
patient exhibited a nerve root injury. At a 6-month follow-up visit,
postoperative Japanese Orthopedic Association (JOA) and visual analog scale (VAS)
scores were evaluated. The mean +/- standard deviation JOA scores were 12.00+/
2.07 for preoperative, 14.73+/-2.05 for 1 week postoperative, 20.07+/-2.32 for 3
months postoperative and 21.75+/-2.18 for 6 months postoperative. The improvement
rate was 16.07, 47.48 and 59.77%, respectively. The mean +/- standard deviation
VAS scores were 6.64+/-1.31 for preoperative, 3.82+/-1.51 for 1 week
postoperative, 2.11+/-1.17 for 3 months postoperative and 1.50+/-1.51 for 6
months postoperative. The JOA and VAS scores improved significantly (P<0.05).
Magnetic resonance imaging and computed tomography were performed preoperatively,
immediately following surgery and at the 6-month postoperative visit to confirm
the efficacy of the resections and evaluate spinal stability. No residual tumors
were identified at follow-up. No alterations in the stability of the spine were
observed postoperatively. The combination of the microsurgical paraspinal keyhole
approach with the tubular retractor system was successful in treating lumbar
intraspinal extramedullary schwannomas. The surgical approach was associated with
decreased hemorrhages, decreased duration of hospital stay, faster recovery and
improved postoperative maintenance of spinal stability.
PMID- 29344233
TI - Lidamycin decreases CD133 expression in hepatocellular carcinoma via the Notch
signaling pathway.
AB - Cluster of differentiation (CD)133 is considered a molecular marker of cancer
stem cells in hepatocellular carcinoma. In the present study, the effect of
lidamycin (LDM) on CD133 expression in hepatocellular carcinoma (Huh7 cells) was
evaluated and the potential molecular mechanism was investigated. Flow cytometry
analysis, as well as sorting, sphere formation and western-blot assays, were
performed in vitro to explore the effects of LDM on CD133 expression. A
subcutaneous tumor model in nude mice was used to observe the effects of LDM on
tumor volume and CD133 protein in vivo. To investigate the potential underlying
molecular mechanism, Notch signaling pathway activity was detected by western
blot analysis and reverse transcription-quantitative polymerase chain reaction.
The proportion of CD133+ cells and the expression of CD133 protein were revealed
to be downregulated by LDM. Sphere formation of sorted CD133+ cells was
suppressed 7 days after LDM treatment. In addition, LDM inhibited tumor volume
formed from sorted CD133+ cells and CD133 protein level in vivo. LDM decreased
the mRNA level of NOTCH1, Hes1 (Hes family BHLH transcription factor 1) and Hey1
(Hes-related family BHLH transcription factor with YRPW motif 1) genes;
consequently, the protein expression of NOTCH1, Notch intracellular domain, Hes1
and Hey1 was decreased by LDM. Downregulation of the Notch signaling pathway by
LDM was enhanced through combination with N-[N-(3,5-difluorophenacetyl)-L-alanyl]
S-phenylglycine t-butyl ester. In brief, these data suggest that LDM suppresses
CD133 expression via the Notch signaling pathway, indicating the potential
mechanism of LDM on CD133 and the benefits for further clinical application.
PMID- 29344234
TI - An oncogenic function of retinoic acid receptor-alpha in the development of
laryngeal squamous cell carcinoma.
AB - The aberrant expression of retinoic acid receptor-alpha (RARalpha) has been
reported in various types of cancer. However, its association with the prognosis
and development of laryngeal squamous cell carcinoma (LSCC) has not yet been
determined. Therefore, the present study aimed to examine the expression and
function of RARalpha in patients with LSCC. The expression of RARalpha in LSCC
tissues was investigated using immunostaining. An MTT assay and flow cytometry
analysis were also performed to investigate the function of RARalpha in the
proliferation and cell cycle of LSCC cells. The expression of RARalpha was
significantly elevated in LSCC tissues compared with adjacent noncancerous
tissues (78.1 vs. 6.3%, P<0.05). The overexpression of RARalpha was associated
with poorly differentiated features of LSCC (P<0.05). Furthermore, the
downregulation of RARalpha inhibited the proliferation of LSCC cells, and
arrested the cell cycle at the G1 phase via upregulation of cyclin dependent
kinase inhibitor 1A, which may be associated with inhibition of the protein
kinase B signaling pathway. Therefore, the overexpression of RARalpha may
contribute to the development of LSCC through the regulation of the cell cycle.
The results of the present study provide evidence that RARalpha serves an
important function in LSCC development and may be a potential therapeutic target
or prognostic predictor for LSCC.
PMID- 29344235
TI - Metronomic chemotherapy remodel cancer-associated fibroblasts to decrease
chemoresistance of gastric cancer in nude mice.
AB - The present study aimed to evaluate whether capecitabine or 5-fluorouracil (5-Fu)
chemotherapy with the metronomic pattern may cause significant chemoresistance
compared with the traditional pattern, and whether CAFs are involved in drug
resistance. SGC-7901 cells were subcutaneously injected into the nude mice, and
the mice were divided into five groups: The control group, intraperitoneally
injected with normal saline; the 5-Fu conventional dose group [5-Fu maximum
tolerated dose (MTD) group], intraperitoneally injected with 50 mg/kg, twice per
week for 2 weeks, with an 1-week discontinuation for 6 weeks; the capecitabine
conventional dose group (capecitabine MTD group), intragastric 500 mg/kg, twice
per week for 2 weeks, with a 1-week discontinuation for 6 weeks; the 5-Fu
metronomic group [5-Fu low-dose metronomic (LDM) group], intraperitoneally
injected with 15 mg/kg, twice a week for 6 weeks; and the capecitabine metronomic
group (capecitabine LDM group), intragastric administration at 200 mg/kg, twice a
week for 6 weeks. The chemotherapy resistance markers [glutathione transferase Pi
(GSTP) and multidrug resistance protein 1 (MDR1)] were detected by
immunohistochemical staining (IHC), and the association of the expression of
these markers with the chemotherapy administration patterns was analyzed.
Vascular endothelial growth factor (VEGF) and the cancer-associated fibroblast
(CAF) marker alpha-smooth muscle actin were also examined by IHC to illustrate
the possible mechanism of chemoresistance. The expression of GSTP and MDR1 in the
MTD groups was significantly higher compared with those of the LDM groups
(P<0.01). Furthermore, the number of CAFs and the level of VEGF in the MTD groups
were significantly higher compared with those of the LDM groups (P<0.05). The low
dose metronomic chemotherapy did not increase the risk of chemoresistance
compared with the conventional dose traditional chemotherapy in terms of
capecitabine or 5-Fu, the increasing amount of CAFs in the microenvironment of
cancer cell following therapy may protect cell from capecitabine or 5-Fu via
producing VEGF to increase vascularization.
PMID- 29344236
TI - Alterations in expression levels of genes in p53-related pathways determined
using RNA-Seq analysis in patients with breast cancer following CIK therapy.
AB - The present study aimed at investigating the underlying molecular mechanisms for
patients following cytokine-induced killer (CIK) therapy, particularly involving
the alterations in p53-associated signaling pathways, to elucidate whether CIK
therapy serves a function in cancer treatment. Samples of blood were collected
from patients with breast cancer prior to and following CIK therapy. Two group
samples were used for RNA sequencing (RNA-Seq) to determine the alterations in
gene expression levels following CIK therapy and one for the quantitative
polymerase chain reaction (qPCR), to analyze the reliability of RNA-Seq results.
The genes that may encode proteins associated with p53 pathways were selected and
analyzed. The expression levels of 8 genes were analyzed, including tumor
suppressor protein 53 (TP53), murine double minute homolog 2 (MDM2), ribosomal
protein L11 (RPL11), ribosomal protein S23 (RPS23), sirtuin 1, histone
deacetylase 1, tuberous sclerosis complex 1 (TSC1) and mechanistic target of
rapamycin (mTOR), and alterations in expression levels following CIK therapy were
determined. However, only RPL11 and RPS23 were identified to exhibit marked
alterations in expression levels (FDR <0.05), which was considered to be due to
individual distinctions. qPCR analysis revealed that the expression levels of the
RPL11, TP53 and TSC1 genes were downregulated, and those of the RPS23 and MDM2
genes were upregulated following CIK therapy. Only MDM2 exhibited a marked
alteration in the gene expression level following CIK therapy. Alterations in the
expression levels of TP53, RPL11 and TSC1 were associated with those of MDM2,
RPS23 and mTOR, respectively.
PMID- 29344237
TI - Chloroform extract of Hedyotis diffusa Willd inhibits viability of human
colorectal cancer cells via suppression of AKT and ERK signaling pathways.
AB - Hedyotis diffusa Willd (HDW) is a widely used traditional Chinese medicine in
clinical therapy to treat various types of cancer, including colorectal cancer
(CRC), but its effective polar fractions and functional mechanisms remain
unclear. The aim of the present study was to determine the most effective extract
of HDW and to investigate its effects on the regulation of CRC cell proliferation
and apoptosis, as well as to investigate the underlying molecular mechanisms. The
results demonstrated that the chloroform extract of HDW (CEHDW) exhibited the
most anticancer ability. Furthermore, results of the MTT assay, colony formation,
carboxyfluorescein diacetate succinimidyl ester assay and annexin V/propidium
iodide staining suggested that CEHDW significantly inhibits proliferation and
promotes apoptosis in the SW620 CRC cell line. Additionally, reverse
transcription-polymerase chain reaction and western blot analysis demonstrated
that CEHDW treatment downregulated the expression of Survivin, proliferating cell
nuclear antigen, Cyclin D1, cyclin-dependent kinase 4 and B-cell lymphoma 2 (Bcl
2), and upregulated the expression of Bcl-2-associated X protein at the mRNA and
protein levels. CEHDW also decreased the phosphorylation of protein kinase B
(AKT) and extracellular-signal-regulated kinase (ERK), which indicated that the
suppression of the AKT and ERK signaling pathways may be one of the underlying
molecular mechanisms by which CEHDW exhibited its anticancer effect. Thus, CEHDW
may be a promising agent for anticancer therapy.
PMID- 29344238
TI - Sophoridine suppresses cell growth in human medulloblastoma through FoxM1, NF
kappaB and AP-1.
AB - Sophoridine is an alkaloid extracted from Sophora alopecuroides that has
extensive pharmacological actions. In the present study, the effect of
sophoridine on cell growth of human medulloblastoma and its mechanism were
investigated. Human medulloblastoma D283-Med cells were incubated with 0, 0.5, 1
or 2 mg/ml sophoridine for 24, 48 or 72 h. Cell proliferation and cytotoxicity
were analyzed using MTT and lactate dehydrogenase assays, respectively. Next,
analyses of cell apoptosis and caspase-3/8 activity were performed using flow
cytometry or spectrophotometry, respectively. Lastly, the change in FoxM1, TrkB,
BDNF, NF-kappaB and AP-1 expression was investigated using western blot analysis.
In the present study, treatment with sophoridine significantly suppressed cell
growth and induced apoptosis in human medulloblastoma cells. In addition,
sophoridine significantly increased cytotoxicity and caspase-3/8 activity in
human medulloblastoma. Finally, it was found that sophoridine suppresses the
protein expression of FoxM1, TrkB, BDNF NF-kappaB and AP-1 in human
medulloblastoma cells. The present study suggests that sophoridine suppresses
cell growth of human medulloblastoma through the inhibition of the FoxM1, NF
kappaB and AP-1 signaling pathway.
PMID- 29344239
TI - Prognostic impact of preoperative serum interleukin-6 levels in patients with
early-stage oral squamous cell carcinoma, defined by sentinel node biopsy.
AB - Failure to detect recurrence and lymph node metastasis early represents a
fundamental barrier to the improvement of survival rate in early stage oral
squamous cell carcinoma (OSCC). The present study evaluated the association
between serum interleukin-6 (IL-6) level and clinical outcomes in patients with
early stage OSCC patients defined by sentinel node biopsy (SNB). A total of 53
patients with clinical stage I/II OSCC who underwent SNB were enrolled. SNB was
determined by a radioisotope method, and was evaluated by histopathological
examination and genetic analysis. Preoperative sera were measured for IL-6 by
ELISA. In the clinical stage I/II patients, disease-free survival (DFS) was
demonstrated to be higher in patients with negative SNB compared with patients
with positive SNB. In total, 13 patients were demonstrated to exhibit lymph node
metastasis by SNB or were reclassified to pathological stage T4 subsequent to
analysis of the surgically resected specimens. Thus, 40 patients were diagnosed
with early stage OSCC. Of these 40 patients, DFS of the patients with low serum
IL-6 was significantly higher compared with the patients with high serum IL-6
(P=0.012). In 19 patients with negative SNB and low serum IL-6, the disease-free
rate was 100%. These findings suggested that SNB staging and serum IL-6 level
have a high prognostic value in patients with early stage OSCC. Additional
investigation and longer follow-up times are warranted to improve understanding
of the group of patients that may benefit from this procedure.
PMID- 29344240
TI - CXCL5 as an autocrine or paracrine cytokine is associated with proliferation and
migration of hepatoblastoma HepG2 cells.
AB - C-X-C motif chemokine ligand 5 (CXCL5) is a CXC-type chemokine that is a crucial
inflammatory mediator and a powerful attractant for granulocytic immune cells.
Increasing evidence has indicated that CXCL5 is involved in the tumorigenesis of
various malignancies. The present investigation demonstrated that CXCL5 was
expressed in both hepatoblastoma HepG2 cells and liver stellate LX-2 cells, and
CXCL5's receptor C-X-C chemokine receptor type 2 (CXCR2) was expressed in HepG2
cells by reverse transcription-polymerase chain reaction (RT-PCR), western
blotting and ELISA assays. Cell counting kit-8, colony formation and Transwell
assays revealed that exogenous CXCL5 expression efficiently promoted
proliferation, colony formation and migration of HepG2 cells. To explore the
autocrine and paracrine roles of CXCL5 in the oncogenic potential of HepG2 cells,
HepG2 cells overexpressing CXCL5 and LX-2 cells overexpressing CXCL5 were
successfully constructed by gene transfection. Similarly, overexpression of CXCL5
in HepG2 also enhanced proliferation, colony formation and migration of HepG2
cells. Furthermore, the condition medium of LX-2 cells overexpressing CXCL5
affected the proliferation and migration of HepG2 cells. RT-PCR and western
blotting assays were also conducted to explore whether overexpression of CXCL5 in
HepG2 modulated the expression of genes. The results revealed that overexpression
of CXCL5 regulated the expression of several genes, including N-myc downregulated
gene 3,w B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein, P53, vascular
endothelial growth factor, interleukin (IL)-18, IL-1beta and cystathionine-gamma
lyase. In conclusion, the present findings indicate that CXCL5/CXCR2 axis
contributes to the oncogenic potential of hepatoblastoma via autocrine or
paracrine pathways by regulating expression of genes associated with the
progression of carcinoma.
PMID- 29344241
TI - Combined pitavastatin and dacarbazine treatment activates apoptosis and autophagy
resulting in synergistic cytotoxicity in melanoma cells.
AB - Melanoma is an aggressive skin cancer and its incidence is increasing faster than
any other type of cancer. Whilst dacarbazine (DTIC) is the standard chemotherapy
for metastatic melanoma, it has limited success. Statins, including pitavastatin,
have been demonstrated to have a range of anti-cancer effects in a number of
human cancer cell lines. The present study therefore explored the anti-cancer
activity of combined DTIC and pitavastatin in A375 and WM115 human melanoma
cells. Cell survival assays demonstrated that combined DTIC and pitavastatin
treatment resulted in synergistic cell death. Cell cycle analyses further
revealed that this combined treatment resulted in a G1 cell cycle arrest, as well
as a sub-G1 population, indicative of apoptosis. Activation of apoptosis was
confirmed by Annexin V-fluorescein isothiocyanate/propidium iodide double
staining and an increase in the levels of active caspase 3 and cleaved poly (ADP
ribose) polymerase. Furthermore, it was demonstrated that apoptosis occurs
through the intrinsic pathway, evident from the release of cytochrome c. Finally,
combined DTIC and pitavastatin treatment was demonstrated to also activate
autophagy as part of a cell death mechanism. The present study provides novel
evidence to suggest that the combined treatment of DTIC and pitavastatin may be
effective in the treatment of melanoma.
PMID- 29344242
TI - In vivo and in vitro induction of the apoptotic effects of oxysophoridine on
colorectal cancer cells via the Bcl-2/Bax/caspase-3 signaling pathway.
AB - Oxysophoridine (OSR) is a major active alkaloid extracted from
Sophoraalopecuroides L. The aim of the present study was to investigate the
induction of the apoptotic effects of OSR on colorectal cancer cells in vivo and
in vitro. The results of the MTT and colony formation assays demonstrated that
the proliferation of HCT116 cells was inhibited by OSR in vitro. The
characteristics of cellular apoptosis in OSR-treated HCT116 cells were analyzed
by Hoechst 33258 staining. It was also observed that the expression of caspase-3,
B-cell lymphoma-2 (Bcl-2) associated X protein (Bax) and cytochrome c increased
significantly upon OSR treatment. However, the expression of Bcl-2 and poly ADP
ribose polymerase-1 (PARP-1) was downregulated in OSR-treated cells compared with
untreated cells. The in vivo experiments identified that OSR significantly
inhibited the growth of the transplanted mouse CT26 tumor tissue, upregulated the
expression of caspase-3, Bax and cytochrome c and downregulated the expression of
Bcl-2 and PARP-1, as detected by reverse transcription-quantitative polymerase
chain reaction and western blotting. It may be concluded that OSR significantly
induced apoptotic effects on colorectal cancer cells in vivo and in vitro, and
that its mechanism may be associated with the Bcl-2/Bax/caspase-3 signaling
pathway.
PMID- 29344243
TI - T-cell immunoglobulin and mucin domain-containing protein-3 and galectin-9
protein expression: Potential prognostic significance in esophageal squamous cell
carcinoma for Chinese patients.
AB - The aim of the present study was to investigate the expression levels of the T
cell immunoglobulin and mucin domain-containing protein-3 (TIM-3) and galectin-9
proteins and their clinical value in esophageal squamous cell carcinoma (ESCC) in
Chinese patients. The expression profiles of TIM-3 and galectin-9 in ESCC were
determined by the immunohistochemical analysis of the postoperative pathological
specimens of 45 patients with ESCC; a chi2 test was used to evaluate the
association of TIM-3 and galectin-9 expression with clinicopathological
parameters, in addition to univariate and multivariate Cox's proportional hazards
model to analyze the prognostic value of the expression of TIM-3 and galectin-9
proteins. The proportion of samples exhibiting a high staining intensity for TIM
3 and galectin-9 were 22.22 and 15.56%, respectively: these samples were termed
the TIM-3 high-expression group (HEG) and galectin-9-HEG. There was a negative
correlation between the expression of TIM-3 and galectin-9 (R=-0.71, P<0.001).
The results of Kaplan-Meier survival analysis led to the conclusion that,
compared with the TIM-3 low expression group (LEG), patients in the TIM-3-HEG
exhibited a poorer overall survival rate (chi2=6.049, P=0.0139). By contrast,
patients in the galectin-9-HEG exhibited a significantly better overall survival
rate than those in the galectin-9-LEG (chi2=4.915, P=0.0266). However, the levels
of TIM-3 and galectin-9 expression were not identified as independent indicators
for the prognosis of patients with ESCC. As high TIM-3 and low galectin-9
expression levels were associated with a poor prognosis for patients with ESCC in
the present study, these proteins may be potential prognostic indicators for
ESCC.
PMID- 29344244
TI - Identification and validation of PSAT1 as a potential prognostic factor for
predicting clinical outcomes in patients with colorectal carcinoma.
AB - The aim of the present study was to explore the existence of known or candidate
drug-target genes that are upregulated in colorectal cancer (CRC) and may serve
as novel prognostic factors or therapeutic targets for this type of malignancy.
An in silico analysis was conducted using the Oncomine tool to compare the
expression levels of a list of drug-target genes between cancerous and normal
tissues in 6 independent CRC cohorts retrieved from the Oncomine database.
Phosphoserine aminotransferase 1 (PSAT1) was identified as the top-ranked
upregulated gene in CRC tumors, and was highly expressed in patients with
chemoresistant disease. Subsequently, the expression of PSAT1 was further
experimentally validated using immunohistochemistry in an independent cohort of
CRC specimens. The immunohistochemistry results demonstrated that PSAT1 was
overexpressed in the CRC tissues compared with the normal colorectal tissues,
which was consistent with the previous in silico analysis. Furthermore, PSAT1
overexpression was associated with response to irinotecan, 5-fluorouracil and
leucovorin chemotherapy, and with shorter survival time, and retained
significance as an independent prognostic factor for CRC when subjected to the
multivariate analysis with a Cox's proportional hazards model. Therefore, the
present results implicate PSAT1 as a potential prognostic biomarker and a
promising therapeutic target for CRC. Targeted PSAT1 inhibition in the treatment
of CRC warrants further investigation.
PMID- 29344245
TI - Overexpression of NEDD9 in renal cell carcinoma is associated with tumor
migration and invasion.
AB - Scaffold protein neural precursor cell expressed, developmentally downregulated 9
(NEDD9) is a member of the Crk-associated substrate protein family and is known
to be a biomarker in multiple cancer types. It serves a critical function in
regulating cell proliferation, migration, invasion and survival. The objective of
this study was to evaluate the potential effects of NEDD9 in renal cell carcinoma
(RCC). The expression of NEDD9 was analyzed by immunohistochemistry, western
blotting and reverse transcription-quantitative polymerase chain reaction. NEDD9
protein and mRNA levels were significantly upregulated in RCC tissues compared
with normal tissues (P<0.001). Furthermore, the NEDD9 immunostaining level was
significantly associated with primary tumor stage and tumor, node, metastasis
stage (P<0.05). High NEDD9 expression resulted in significantly lower survival
rates for patients compared with normal NEDD9 expression (P<0.01). In addition,
wound healing and transwell assays indicated that NEDD9 depletion by small
interfering RNA significantly attenuated the migration and invasion of RCC cells
(P<0.001). The present data suggested that NEDD9 may be a novel target for
prevention and treatment of RCC metastasis and recurrence.
PMID- 29344246
TI - Silibinin inhibits migration and invasion of the rhabdoid tumor G401 cell line
via inactivation of the PI3K/Akt signaling pathway.
AB - Rhabdoid tumors, which tend to occur prior to the age of 2 years, are one of the
most aggressive malignancies and have a poor prognosis due to the frequency of
metastasis. Silibinin, a natural extract, has been approved as a potential tumor
suppressor in various studies, however, whether or not it also exerts its
antitumor capacity in rhabdoid tumors, particularly with regards to tumor
migration and invasion, is unclear. The rhabdoid tumor G401 cell line was used in
the present in vitro study. An MTT assay was used to assess the cytotoxicity of
silibinin on G401 cells, cell migration was studied using a wound healing assay
and a Transwell migration assay, and cell invasion was determined using a
Transwell invasion assay. The underlying mechanism in silibinin inhibited cell
migration and invasion was investigated by western blot analysis and further
confirmed using a specific inhibitor. Experimental results demonstrated that high
doses of silibinin suppressed cell viability, and that low doses of silibinin
inhibited cell migration and invasion without affecting cell proliferation. The
phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway was
involved in the silibinin-induced inhibition of metastasis. Silibinin inactivated
the PI3K/Akt pathway, and inhibited cell migration and invasion, an effect that
was further enhanced when LY294002, a classic PI3K inhibitor, was used
concurrently. In general, silibinin inhibits migration and invasion of the
rhabdoid tumor G401 cell line via inactivation of the PI3K/Akt signaling pathway
and may be a potential chemotherapeutic drug to combat rhabdoid tumors in the
future.
PMID- 29344247
TI - Upregulation of the checkpoint protein CHFR is associated with tumor suppression
in pancreatic cancers.
AB - The checkpoint with forkhead-associated (FHA) domain and RING-finger (CHFR)
protein was identified as a cell cycle checkpoint protein and E3 ubiquitin
ligase. In the present study, the potential functions of CHFR in pancreatic
cancer were investigated. CHFR expression was measured in five pancreatic cancer
cell lines by reverse transcription- quantitative polymerase chain reaction and
western blotting. Capan-1 cells stably expressing CHFR were established by
lentiviral vector transfection. Cell proliferation was assessed using Cell
Counting Kit-8, and cell migration/invasion assay was determined using Transwell
assays. Cell cycle and apoptosis induced by gemcitabine or docetaxel were
evaluated using flow cytometry. CHFR expression levels were also evaluated in
pancreatic ductal adenocarcinoma (PDAC) tumor samples as well as adjacent non
tumor tissues by immunohistochemistry. The significance of CHFR expression was
determined, with respect to clinicopathological features and overall survival.
Overexpression of CHFR in Capan-1 cells led to a decreased proliferative rate and
reduced cell migration and invasion abilities. Results also indicated an increase
in G1 phase cells in Capan-1 cells overexpressing CHFR. Docetaxel-induced
apoptosis was inhibited in Capan-1 cells with CHFR-overexpression. A reduction in
CHFR expression was detected in 51.9% of patients with PDAC, which significantly
correlated with later T-stage. The results show CHFR functions as a tumor
suppressor in pancreatic cancer, suggests its potential role in controlling the
cell cycle of pancreatic cancer cells; however, CHFR overexpression is not a
favorable factor in apoptosis induced by docetaxel.
PMID- 29344248
TI - Survival prediction in patients with resectable colorectal liver metastases:
Clinical risk scores and tumor response to chemotherapy.
AB - Clinical risk scores and response to pre-operative chemotherapy are prognostic
factors of colorectal liver metastases. The aim of the present study was to
evaluate the effectiveness of combining these factors to predict patient survival
and to select patients for curative therapy. The study included 189 patients who
underwent hepatectomy following neo-adjuvant chemotherapy, for initially
resectable colorectal liver metastases, between January 2005 and December 2015.
Patients were stratified into four sub-groups: A1-2, low clinical risk scores
with/without a response to pre-operative chemotherapy; and B1-2, high clinical
risk scores with or without a response to pre-operative chemotherapy. Treatment
and survival data were analysed. Survival was significantly longer in patients
with low clinical risk scores and a response to pre-operative chemotherapy; these
factors were confirmed as independent prognostic factors by multivariate
analysis. Combining clinical risk score and chemotherapy response classification,
patient survival was significantly longer for groups A1-2/B1 compared with for
group B2, in which only 10.2% of patients were alive after 5 years. Of those with
no response to first-line chemotherapy, survival was significantly longer in
patients who responded to second-line chemotherapy. A combined clinical risk
score and chemotherapy response classification may aid in identifying suitable
candidates for potentially curative therapy.
PMID- 29344249
TI - Estradiol suppresses phosphorylation of ERalpha serine 167 through upregulation
of PP2A in breast cancer cells.
AB - Aromatase inhibitors (AIs) are effective endocrine therapeutics for
postmenopausal women with estrogen receptor (ER)alpha-positive breast cancer.
However, the efficacy of the treatment is often limited by the onset of AI
resistance, owing to the phosphorylation of ERalpha serine 167 (Ser167). Previous
studies have indicated that hyperactivation of the phosphoinositide-3 kinase/RAC
serine/threonine-protein kinase signaling pathway occurs in AI-resistant breast
cancer models, which coincides with elevated levels of ERalpha phosphorylation at
Ser167. The tumor suppressor serine/threonine-protein phosphatase 2A (PP2A)
regulates the phosphatidylinositol 3-kinase/RAC serine/threonine-protein kinase
signaling pathway. A previous study indicated that PP2A inhibition decreased
ERalpha Ser167 phosphorylation and estradiol (E2)-independent cell growth. The
present study investigated the potential relevance of PP2A in E2 deprivation
resistant MCF-7 cells. E2 depletion reduced the susceptibility of MCF-7 cells to
inhibitors of mechanistic target of rapamycin (mTOR) and significantly increased
ERalpha Ser167 phosphorylation and decreased expression of PP2A. Conversely, long
term E2-deprived (LTED) MCF-7 cells, a model of AI-resistant breast cancer,
exhibited decreased ERalpha Ser167 phosphorylation and further upregulation of
PP2A in E2-containing medium. The PP2A activator forskolin (FSK) significantly
inhibited LTED cell proliferation by increasing the effect of everolimus (Eve),
an mTOR inhibitor. In summary, the present study provides further evidence that
PP2A represents a therapeutic target for AI-resistant breast cancer.
PMID- 29344250
TI - Prevention of body weight loss and sarcopenia by a novel selective androgen
receptor modulator in cancer cachexia models.
AB - Cancer cachexia is a syndrome that impairs the quality of life and overall
survival of patients, and thus the effectiveness of anticancer agents. There are
no effective therapies for cancer cachexia due to the complexity of the syndrome,
and insufficient knowledge of its pathogenesis results in difficulty establishing
appropriate animal models. Previously, promising results have been obtained in
clinical trials using novel agents including the ghrelin receptor agonist
anamorelin, and the selective androgen receptor modulator (SARM) enobosarm to
treat cachexia in patients with cancer. The present study examined the
pharmacological effects of SARM-2f, a novel non-steroidal small molecule SARM, in
animal models. SARM-2f increased body and skeletal muscle weight without
significantly increasing the weight of the seminal vesicles or prostates of the
castrated male rats. In the mice with tumor necrosis factor alpha-induced
cachexia, SARM-2f and TP restored body weight, carcass weight, and food
consumption rate. In the C26 and G361 cancer cachexia animal models, body and
carcass weight, lean body mass, and the weight of the levator ani muscle were
increased by SARM-2f and TP treatments. Tissue selectivity of SARM-2f was also
observed in these animal models. The results demonstrate the anabolic effects of
SARM-2f in a cytokine-induced cachexia model and other cancer cachexia models,
and suggest that SARM-2f may be a novel therapeutic option for cachexia in
patients with cancer.
PMID- 29344251
TI - miR-218 inhibits acute promyelocytic leukemia cell growth by targeting BMI-1.
AB - Acute promyelocytic leukemia (APL) is a subtype of acute myelocytic leukemia.
Previous studies have reported a number of functions and therapeutic roles of
microRNAs (miRs) in APL, and have suggested that miR-218 acts as a tumor
suppressor in a number of types of human cancer; however, its role in APL remains
unclear. In the present study, the expression of miR-218 and its effects on the
viability and proliferation of HL-60 cells was investigated. Reverse
transcription-quantitative polymerase chain reaction analysis demonstrated that
miR-218 was frequently downregulated in APL marrow tissues compared with normal
marrow tissues. Overexpression of miR-218 significantly inhibited cell
proliferation, arrested the cell cycle in the G0/G1 phase and induced apoptosis.
In addition, B-cell-specific Moloney murine leukemia virus integration site 1
(BMI-1) mRNA expression was negatively associated with miR-218 expression; BMI-1
mRNA and protein expression were downregulated following transfection with miR
218 mimic. These results indicate that miR-218 functions as tumor suppressor in
APL, and the miR-218/BMI-1 signaling axis may be a potential novel diagnostic
marker and therapeutic target for the treatment of APL.
PMID- 29344252
TI - iTRAQ-based quantitative proteomic analysis and bioinformatics study of proteins
in retinoblastoma.
AB - The aim of the present study was to analyze proteins in the aqueous humor (AH) of
patients' retinoblastoma (RB), and investigate their potential role in RB using
the comparative proteomic technique of isobaric tags for relative and absolute
quantitation (iTRAQ) coupled with offline two-dimensional liquid chromatography
tandem mass spectrometry. A total of 0.1 ml AH was collected from 10 children
with RB (mean age, 3.8 years; range, 2-5 years) and patients with senile
cataracts (mean age, 70.4 years; range, 65-79 years), which was used as the
control. iTRAQ was used to analyze proteins in the AH of patients and controls.
Proteins with a fold change of >1.20 or <0.83 were considered to be significantly
differentially expressed (with corrected P<0.05). The identified proteins were
subjected to subsequent gene ontology (GO) analysis using the DAVID database. A
total of 83 proteins that were expressed differently between the controls and
patients' AH samples were identified using iTRAQ analysis. Of these proteins, 44
were upregulated and 39 were downregulated. On the basis of biological processes
in GO, the identified proteins were primarily involved in glycoprotein, amyloid
acute-inflammatory and defensive responses. Among these proteins, pigment
epithelium-derived factor serves a potential role in the treatment of RB, and
stimulated by retinoic acid 6 may serve as a potential protein involved in RB
development. To the best of our knowledge, the present study is the first to
identify 83 proteins associated with RB using iTRAQ technology. The results of
the present study will aid in furthering the understanding of RB and developing
novel therapy targets in the future.
PMID- 29344253
TI - Diagnostic value of medical thoracoscopy in malignant pleural effusion induced by
non-Hodgkin's lymphoma.
AB - Malignant pleural effusion (MPE) appears in up to 20% of patients with non
Hodgkin's lymphoma (NHL). The present study aimed to assess the efficacy of
medical thoracoscopy (MT) in the diagnosis of patients with MPE induced by NHL.
Between July 2005 and June 2014, 833 patients with pleural effusions of unknown
etiology underwent MT in Beijing Chaoyang Hospital (Beijing, China), where
diagnostic thoracocentesis or/and blind pleural biopsy had failed to yield an
answer. Demographic, radiographic, thoracoscopic, histological and
immunophenotyping data of 10 NHL patients with MPE were then retrospectively
analyzed. Under medical thoracoscopy, pleural nodules (in n=6 patients),
hyperemia (n=5), plaque-like lesions (n=4), pleural thickening (n=3), cellulose
(n=3), ulcer (n=2), adhesion (n=2), and scattered hemorrhagic spots (n=1) were
observed on the surface of parietal pleura. Histopathological and
immunohistochemical analysis of pleural biopsy samples led to a correct diagnosis
of B-cell NHL in 7 patients and T-lymphoblastic NHL in 2 patients. Data from the
present study demonstrated that pleural biopsy through MT achieved a definite
diagnosis of NHL in 9 out of 10 (90%) patients with MPE induced by NHL.
Therefore, MT is a useful method for diagnosing MPE induced by NHL.
PMID- 29344254
TI - Inhibitory effect of the low-toxic exogenous aryl hydrocarbon receptor modulator
3'3-diindolylmethane on gastric cancer in mice.
AB - 3'3-Diindolylmethane (DIM) has been proved to exhibit anticancer properties in
many solid tumors. In our previous study, we demonstrated that DIM inhibited
SGC7901 cell proliferation by inducing apoptosis and delaying cell cycle
progression. Herein, we further explored the anti-tumor effect of DIM on SGC-7901
tumor bearing mice. Tumors were excised, weighed, and tested by western blot and
TdT-UTP nick-end labeling (TUNEL) assay. Blood samples were collected for
biochemical analysis. The expression levels of AhR and cytochrome P450, family 1,
subfamily A, polypeptide 1 (CYP1A1) protein were evaluated by western-blot assay.
Our data show that with the increase of DIM dose (0, 5, 10, 20 mg/kg/day), AhR
protein gradually decreased as CYP1A1 protein increased. The weight of the tumors
found in the treated animals was significantly lower than that of the control
group (0.845+/-0.096 vs. 1.275+/-0.236 g, 0.768+/-0.161 vs. 1.275+/-0.236 g,
0.607+/-0.106 vs. 1.275+/-0.236 g, P<0.05). TUNEL test showed that DIM induced
increased apoptosis in the treatment groups in a dose-dependent manner. Blood
tests also indicated that DIM showed no toxic effect on animal weight or liver
and kidney function. These results indicated that DIM agent could be a safe and
potent drug in therapy of gastric cancer.
PMID- 29344255
TI - Plasma olfactomedin 4 level in peripheral blood and its association with clinical
features of breast cancer.
AB - The present study aimed to investigate the expression of olfactomedin 4 (OLFM4)
in plasma of patients with breast cancer and its association with diagnosis,
metastasis and prognosis of breast cancer. OLFM4 gene expression level of
peripheral blood plasma in 60 patients with breast cancer and 26 healthy donors
was examined by ELISA. The expression of OLFM4 in tumor tissues of patients with
breast cancer was evaluated by immunohistochemistry (protein expression) and
reverse transcription-quantitative polymerase chain reaction (mRNA expression),
respectively. Circulating tumor cells (CTCs) were detected in a certain set of
patients. The expression of OLFM4 in plasma of the overall healthy people was
higher compared with patients with breast cancer. The plasma OLFM4 level in
patients with breast cancer was consistent with the expression of OLFM4 protein
in tumor tissues (R2=1), indicating that the level of plasma OLFM4 expression may
represent the expression of OLFM4 in breast cancer tissues. The plasma OLFM4
level in patients with histological grade I was significantly lower compared with
grade III (P<0.05). Breast cancer patients with positive CTC were associated with
low level of plasma OLFM4. These results suggest that low OLFM4 expression in
plasma or tissue specimens of breast cancer patients is more likely to represent
low histological differentiation and decreased invasive/metastatic capabilities.
Taken together, plasma OLFM4 level may be considered as a biomarker for diagnosis
and prognosis of breast cancer for cases where there are difficulties in
obtaining tumor tissue samples.
PMID- 29344256
TI - Pien Tze Huang inhibits the growth of hepatocellular carcinoma cells by
upregulating miR-16 expression.
AB - Hepatocellular carcinoma (HCC) is characterized by uncontrolled proliferation and
the deregulation of apoptotic signaling, although its molecular pathogenesis is
not fully characterized. The ability to inhibit excessive proliferation and
induce the apoptosis of cancer cells are crucial characteristics of anticancer
drugs. Pien Tze Huang (PZH) is a widely used traditional Chinese medicine for the
treatment of various types of cancer, and has exhibited promising therapeutic
effects in clinical trials of HCC. However, the underlying mechanisms for its
action are unclear. In the present study, the aim was to explore the effect of
PZH on the proliferation and apoptosis of the BEL-7402 HCC cell line, and the
associated mechanisms. PZH treatment significantly inhibited BEL-7402 cell
viability, confluence and clonogenicity, inducing cell cycle arrest and promoting
apoptosis. In addition, PZH treatment suppressed the expression of the pro
proliferative genes cyclin D1 and cyclin-dependent kinase 4, and decreased the
expression of the anti-apoptotic gene Bcl-2. PZH treatment also upregulated the
expression of a key microRNA (miR), miR-16. The study demonstrated that PZH can
effectively inhibit cancer cell proliferation and induce apoptosis in BEL-7402
HCC cells via the upregulation of the tumor suppressor miR-16.
PMID- 29344257
TI - Involvement of soluble B7-H3 in combination with the serum inflammatory cytokines
interleukin-17, -8 and -6 in the diagnosis of hepatocellular carcinoma.
AB - Previous studies have demonstrated that B7-H3, and the inflammatory cytokines
interleukin (IL)-17, IL-8 and IL-6, are involved in the development of a variety
of tumors. The objectives of the present study were: i) To investigate the
association between soluble B7-H3 (sB7-H3) and cytokine levels of IL-17, IL-8 and
IL-6 in the serum of patients with hepatocellular carcinoma (HCC); and ii) to
determine their potential value for use in HCC diagnosis. Serum sB7-H3, IL-17, IL
8 and IL-6 levels in the HCC patients and healthy control subjects were measured
using ELISA. The accuracy of each of these biomarkers in HCC diagnosis was
compared using a receiver operating characteristic curve and the area under the
curve (AUC). A logistic regression model was used to investigate the accuracy of
diagnosing HCC when evaluated using combined determinations of sB7-H3, IL-17, IL
8 and IL-6 levels. The data demonstrated that serum levels of sB7-H3, IL-17, IL-8
and IL-6 were significantly increased in HCC patients compared with those in the
healthy control group. Serum sB7-H3 levels were positively associated with serum
IL-17, whereas serum IL-8 levels were negatively correlated with serum IL-17
levels. The AUC values for sB7-H3, IL-17, IL-8 and IL-6 were 83.2, 65.7, 95.3 and
97.0%, respectively, and indicated that all four biomarkers exhibited a
statistically significant capacity for diagnosing HCC. Using the logistic
regression model, the AUC value, sensitivity and specificity, as determined for
the combination of the four biomarkers, were 99.2, 96.67 and 97.14%,
respectively. This was significantly greater than that achieved when any single
biomarker was used alone in the logistic regression model to assess their
accuracy in HCC diagnosis. The optimum cutoff value of the predicted probability
obtained by the combination of sB7-H3, IL-17, IL-8 and IL-6 in the regression
model was 0.5745. To conclude, the present study revealed that there exists a
positive association between serum sB7-H3 and IL-17 levels in HCC patients.
Determinations involving the combination of serum sB7-H3, IL-17, IL-8 and IL-6
levels demonstrate great potential for use in HCC diagnosis.
PMID- 29344258
TI - Involvement of breast cancer stem cells in tumor angiogenesis.
AB - The aim of the present study was to investigate the role of breast cancer stem
cells (BCSCs) in the angiogenesis of breast cancer tumors. The expression levels
of mutant p53, cluster of differentiation (CD)31, vascular endothelial factor
(VEGF), in addition to human epidermal growth factor (HER)2, were detected in the
blood vessels of human breast cancer (BC) tissue samples. CD44+/CD24-/low cells
were selected from single-cell suspensions of BC tissues to assess the expression
of CD31 and CD105, in addition to the ability of these cells to metabolize
acetylated low-density lipoprotein (Ac-LDL). Furthermore, vascular-like
structures were observed histologically. Mutant p53, CD31 and VEGF were all
expressed in these tissues. CD44+ cells comprised 7.5+/-2.6 and 94.3+/-4.7% of
the cell population prior to and following sorting, respectively. CD24+ cells
comprised 48.2+/-9.4 and 4.3+/-4% of the cell population prior to and following
sorting, respectively. A low proportion of CD24+ cells corresponded to a high
proportion of CD24-/low cells. The percentages of CD105+ and CD31+ glomus cells
in the mammary gland were 4.5+/-0.9 and 6.2+/-1.3%, respectively, and following
passaging for three generations, these increased to 79.6+/-9.3 and 84.1+/-10.7%,
respectively (P<0.05). Cells were cultured using an endothelial cell culture
system, and they internalized DiL-Ac-LDL. Here, vascular endothelial cells formed
vascular-like structures, whereas the control group demonstrated no such
structures. Overall, the results suggest that BCSCs-derived endothelial cells may
contribute to tumor angiogenesis.
PMID- 29344259
TI - Lesions of the central nervous system in leukemia: Pathological and magnetic
resonance imaging features at presentation in 14 patients.
AB - The present study aimed to characterize the specific pathology and magnetic
resonance imaging (MRI) findings observed in patients with leukemia with central
nervous system (CNS) lesions, and to determine their value in the management of
such patients. Lesions of the CNS were observed during and following treatment of
leukemia. The data from stereotactic biopsy-proven pathology (12 patients) and
MRI examinations (14 patients) were retrospectively evaluated. Proton-magnetic
resonance-spectroscopy was performed in three patients. Factors that predisposed
to lesions of the CNS were reviewed from the patient medical records. Among the
14 patients, eight had CNS leukemia, four had a CNS infection and two had a
neurodegenerative disorder (one leukoencephalopathy and one glial cell
hyperplasia). The clinical diagnosis based on clinical symptoms, signs and MRI
features was not consistent with the pathological diagnosis in two patients. In
one patient, the clinical diagnosis was a CNS infection; however, the patient's
pathological diagnosis was CNS leukemia. In the other patient, the clinical
diagnosis was CNS leukemia, but the pathological diagnosis was glial cell
hyperplasia. CNS lesions in leukemia have a wide range of causes. Apart from the
relapse of leukemia in the CNS, there are treatment-associated neurotoxicities
and infections that are caused by immunocompromised states. As numerous leukemia
associated CNS lesions are treatable, early diagnosis is essential.
PMID- 29344260
TI - DR2 blocker thioridazine: A promising drug for ovarian cancer therapy.
AB - Dopamine receptor 2 (DR2) may be a biomarker for various types of cancer. Ovarian
cancer cells overexpress DR2; therefore, blocking DR2 may be a novel treatment
strategy for ovarian cancer. Thioridazine, a DR2 blocker, has antineoplastic
activity in a variety of cancer cells. In view of the requirement for novel
therapeutic agents in ovarian cancer, the present study aimed to determine the
potential effects of thioridazine in vitro and in vivo. It was revealed that the
DR2 blocker thioridazine induced cell death in a dose-dependent manner in ovarian
cancer cells. Thioridazine treatment induced apoptosis and autophagy, which may
be attributed to an increased level of reactive oxygen species and associated DNA
damage. Additionally, the expression of various proteins increased with oxidative
stress, including nuclear factor E2-related factor 2, which is a pivotal
transcriptional factor involved in cellular responses to oxidative stress. Heme
oxygenase 1, NAPDH quinone dehydrogenase 1 and hypoxia inducible factor-1alpha
and phosphorylated (p)-protein kinase B expression was significantly decreased,
and the expression level of p-extracellular signal-related kinases and p-P38 was
increased. Using 3-methyl adenine to inhibit autophagy caused the rate of
apoptosis to increase. Thioridazine inhibited the growth of SKOV3 xenografts in
nude mice. The present study demonstrated that the DR2 blocker thioridazine
exhibited anticancer effects in vitro and in vivo, suggesting that thioridazine
may be used as a potential drug in ovarian cancer therapy.
PMID- 29344261
TI - T cell acute lymphoblastic lymphoma complicated with myeloid sarcoma in an adult:
A case report.
AB - The present case report describes a rare case of T cell acute lymphoblastic
lymphoma (T-LBL) in the lymph node with myeloid sarcoma in the pericardium. A 33
year-old Chinese male was admitted to hospital on 4 July 2015 exhibiting a fever
and having experienced wheezing and fatigue for the previous 7 days. Routine
pathological, computed tomographic, cytological and immunophenotypic observations
revealed a diagnosis of T-LBL in the lymph node on 7 August 2015, without
evidence of bone marrow (BM) involvement. The patient received induction
chemotherapy for T-LBL and achieved partial remission. The patient was identified
to have multiple serous effusion and analysis of pericardial effusion cells
revealed the diagnosis of T-LBL with extramedullary myeloid sarcoma (without BM
involvement) on 25 November 2015. On 30 December 2015, the patient was identified
to exhibit proliferation of primary myeloid cells in the peripheral blood and BM,
and an abnormal karyotype in BM cells, indicating that the complicated myeloid
sarcoma involved the BM. No matched donor was available so the patient received
chemotherapy to manage the disease. The patient was discharged on 31 January 2016
and ceased treatment. The patient succumbed on 19 February 2016 at home. To the
best of our knowledge, T-LBL complicated with myeloid sarcoma had not been
previously reported in Chinese adult male patients. In addition, the involvement
of the BM and aberrant karyotype of the complicated myeloid sarcoma in the
patient were rare.
PMID- 29344262
TI - Hedyotis diffusa willd extract suppresses colorectal cancer growth through
multiple cellular pathways.
AB - The development of colorectal cancer (CRC) is strongly associated with the
imbalance of various intracellular signal transduction cascades, including
protein kinase B (AKT), mitogen-activated protein kinase 1 (MAPK), signal
transducer and activator of transcription 3 (STAT3), as well as crosstalk between
these signaling networks. At present, anti-tumor agents are often single-targeted
and therefore are not always therapeutically effective. Moreover, long-term use
of these anti-tumor agents often generates drug resistance and potential side
effects. These problems highlight the urgent need for the development of novel
and more effective anti-cancer drugs. Hedyotis diffusa Willd (HDW) has been used
as a major component in traditional Chinese medicine for the clinical treatment
of colorectal cancer, with a limited number of adverse effects. However, the
molecular mechanisms, which underlie its anti-cancer activity, still require
further elucidation. In the present study, using xenograft models and various
different human CRC cell lines, the efficacy of the ethanol extract of HDW
(EEHDW) against tumor growth was evaluated, and its underlying molecular
mechanisms of action were investigated. It was demonstrated that EEHDW was able
to inhibit cancer growth in vivo and in vitro. Furthermore, EEHDW was able to
suppress the activation of several CRC-associated signaling pathways and was able
to regulate the expression of various inflammatory and angiogenic factors. This
resulted in the induction of apoptosis and inhibition of cellular proliferation,
as well as tumor angiogenesis. The present study demonstrated that EEHDW is able
to exhibit anti-cancer activity due to its ability to affect multiple
intracellular targets, which suggests that it may be a novel multi-potent
therapeutic agent for the treatment of colorectal cancer.
PMID- 29344263
TI - Thalidomide inhibits proliferation and epithelial-mesenchymal transition by
modulating CD133 expression in pancreatic cancer cells.
AB - Pancreatic cancer is a solid malignancy with a high mortality rate, on account of
the high incidence of metastasis at the time of detection. The aggressiveness of
pancreatic cancer may be partly driven by cancer stem cells (CSCs), which are
characterized by the ability to self-renew and recapitulate tumors in the ectopic
setting. However, although a number of drugs targeting CSCs are currently under
clinical investigation, few effective drugs have been developed. The present
study demonstrated that thalidomide inhibited cell proliferation and metastasis
in pancreatic cancer cell lines through the inhibition of epithelial mesenchymal
transition. The effect of thalidomide was more pronounced in cluster of
differentiation 133 (CD133)+ SW1990 cells than in Capan-2 cells, in which CD133
expression was almost undetectable. The results revealed that CD133 is likely to
serve a role in the antitumor effect of thalidomide and indicated that
thalidomide could be developed as a CSC-specific adjuvant chemotherapy in
pancreatic cancer.
PMID- 29344264
TI - Preclinical and clinical implications of TERT promoter mutation in glioblastoma
multiforme.
AB - The promoter region of the telomerase reverse transcriptase gene (TERT) is
mutated in a subpopulation of patients with glioblastoma multiforme (GBM). In the
present study, preclinical and clinical implications of the mutation were
analyzed in 25 GBMs to evaluate its utility as a therapeutic target. Associations
between the TERT promoter mutation and a number of preclinical/clinical
characteristics were analyzed. Notably, the TERT promoter mutation was identified
in 92.3% of GBMs where dissociated cells revealed in vitro sphere formation
capacity; while the TERT promoter mutation was identified in 33.3% of GBMs
without in vitro sphere formation capacity (P=0.004). In addition, this
significantly increased mutation rate was observed in GBMs with in vivo
tumorigenic potential (80% vs. 0%; P=0.004). Furthermore, patients with GBM
exhibiting the TERT promoter mutation demonstrated significantly decreased
overall survival rate compared with patients lacking this mutation (81.7 vs.
152.6 weeks; P=0.026). The results of the present study indicated that the TERT
promoter mutation is associated with the self-renewal capacity of GBM cells and
clinical aggressiveness of GBMs, which may be translated to a targeting therapy
against TERT to inhibit the self-renewal of GBM cells.
PMID- 29344265
TI - High expression of PU.1 is associated with Her-2 and shorter survival in patients
with breast cancer.
AB - The transcription factor PU.1 was previously identified as an oncogene or a tumor
suppressor in different types of leukemia. The aim of the present study was to
investigate the expression of PU.1 in breast cancer and to analyze its
association with clinical features and prognosis. Immunohistochemistry was used
to determine PU.1 expression in breast cancer tissue microarrays and paraffin
embedded sections. The association between PU.1 expression and
clinicopathological factors was assessed by using chi-square test. The survival
analysis of patients was conducted by using Kaplan-Meier analysis and log-rank
tests. Cox regression was utilized for univariate and multivariate analyses of
prognostic factors. The results indicated that the expression level of PU.1
protein in breast cancer samples was significantly higher compared with normal
breast tissues (P=2.63*10-8). Furthermore, the level of PU.1 expression was
detected to be positively associated with androgen receptor (P=0.027) and human
epidermal growth factor receptor 2 status (P=2.03*10-21) as well as molecular
subtype (P=3.51*10-11). Furthermore, patients with negative PU.1 expression had
longer OR compared with those with positive PU.1 expression (P=3.67*10-4).
Multivariate Cox regression analysis revealed that PU.1 expression level and
tumor-node-metastasis stage were independent prognostic factors for overall
survival (P=0.034 and P=0.018, respectively). Therefore, PU.1 protein expression
may contribute to breast cancer progression and may be a valuable molecular
marker to predict the prognosis of patients with breast cancer.
PMID- 29344266
TI - Erratum: HBV suppresses thapsigargin-induced apoptosis via inhibiting CHOP
expression in hepatocellular carcinoma cells.
AB - [This corrects the article DOI: 10.3892/ol.2017.6666.].
PMID- 29344268
TI - Interferon-gamma and Colorectal Cancer: an up-to date.
AB - Colorectal cancer still remains the third cause of cancer death among cancer
patients. Early diagnosis is crucial and they can be either endoscopic or with
blood biomarkers. Endoscopic methods consist of gastroscopy and colonoscopy,
however; in recent years, endoscopic ultrasound is being used. The
microenvironment is very important for the successful delivery of the treatment.
Several proteins and hormones play a crucial role in the efficiency of the
treatment. In the current mini review we will focus on interferon-gamma.
PMID- 29344270
TI - Lenvatinib in Advanced Radioiodine-Refractory Thyroid Cancer - A Retrospective
Analysis of the Swiss Lenvatinib Named Patient Program.
AB - Purpose: Differentiated thyroid cancer (DTC) accounts for approximately 95% of
thyroid carcinomas. In the metastatic RAI-refractory disease, chemotherapy has
very limited efficacy and is associated with substantial toxicity. With
increasing knowledge of the molecular pathogenesis of DTC, novel targeted
therapies have been developed. Lenvatinib is a tyrosine kinase inhibitor (TKI)
with promising clinical activity based on the randomized phase III SELECT trial.
In Switzerland, a Named Patient Program (NPP) was installed to bridge the time
gap to Swissmedic approval. Here, we report the results from the Swiss Lenvatinib
NPP including patients with metastatic RAI-refractory DTC. Methods: Main
inclusion criteria for the Swiss NPP were RAI-refractory DTC, documented disease
progression, Eastern Cooperative Oncology Group (ECOG) performance status 0-3.
The number of previous therapies was not limited. The Swiss Lenvatinib NPP was
initiated in June 2014 and was closed in October 2015 with the approval of the
drug. Results: Between June 2014 and October 2015, 13 patients with a median age
of 72 years have been enrolled. Most patients (69%) had at least one prior
systemic therapy, mainly sorafenib. 31% of patients showed a PR and 31% SD.
Median progression free survival was 7.2 months and the median overall survival
was 22.7 months. Dose reduction due to adverse events was necessary in 7 patients
(53%). At the time of analysis 6 patients (47%) were still on treatment with a
median time on treatment of 9.98 months. Conclusions: Our results show that
lenvatinib has reasonable clinical activity in unselected patients with RAI
refractory thyroid cancer with nearly two-third of patients showing clinical
benefit. The toxicity profile of lenvatinib is manageable.
PMID- 29344267
TI - Break Breast Cancer Addiction by CRISPR/Cas9 Genome Editing.
AB - Breast cancer is the leading diagnosed cancer for women globally. Evolution of
breast cancer in tumorigenesis, metastasis and treatment resistance appears to be
driven by the aberrant gene expression and protein degradation encoded by the
cancer genomes. The uncontrolled cancer growth relies on these cellular events,
thus constituting the cancerous programs and rendering the addiction towards
them. These programs are likely the potential anticancer biomarkers for
Personalized Medicine of breast cancer. This review intends to delineate the
impact of the CRSPR/Cas-mediated genome editing in identification and validation
of these anticancer biomarkers. It reviews the progress in three aspects of
CRISPR/Cas9-mediated editing of the breast cancer genomes: Somatic genome
editing, transcription and protein degradation addictions.
PMID- 29344269
TI - Early and Partial Reduction in CD4+Foxp3+ Regulatory T Cells during Colitis
Associated Colon Cancer Induces CD4+ and CD8+ T Cell Activation Inhibiting
Tumorigenesis.
AB - Colorectal cancer (CRC) is the second most commonly diagnosed cancer in women and
the third in men in North America and Europe. CRC is associated with inflammatory
responses in which intestinal pathology is caused by different cell populations
including a T cell dysregulation that concludes in an imbalance between activated
T (Tact) and regulatory T (Treg) cells. Treg cells are CD4+Foxp3+ cells that
actively suppress pathological and physiological immune responses, contributing
to the maintenance of immune homeostasis. A tumor-promoting function for Treg
cells has been suggested in CRC, but the kinetics of Treg cells during CRC
development are poorly known. Therefore, using a mouse model of colitis
associated colon cancer (CAC) induced by azoxymethane and dextran sodium sulfate,
we observed the dynamic and differential kinetics of Treg cells in blood, spleen
and mesenteric lymph nodes (MLNs) as CAC progresses, highlighting a significant
reduction in Treg cells in blood and spleen during early CAC development, whereas
increasing percentages of Treg cells were detected in late stages in MLNs.
Interestingly, when Treg cells were decreased, Tact cells were increased and vice
versa. Treg cells from late stages of CAC displayed an activated phenotype by
expressing PD1, CD127 and Tim-3, suggesting an increased suppressive capacity.
Suppression assays showed that T-CD4+ and T-CD8+ cells were suppressed more
efficiently by MLN Treg cells from CAC animals. Finally, an antibody-mediated
reduction in Treg cells during early CAC development resulted in a better
prognostic value, because animals showed a reduction in tumor progression
associated with an increased percentage of activated CD4+CD25+Foxp3- and
CD8+CD25+ T cells in MLNs, suggesting that Treg cells suppress T cell activation
at early steps during CAC development.
PMID- 29344271
TI - Clinical-pathological Characteristics and Prognostic Factors for Papillary
Thyroid Microcarcinoma in the Elderly.
AB - Background: The incidence of papillary thyroid microcarcinoma (PTMC) has
increased dramatically over the past three decades worldwide. The annual rate of
increase in the elderly (>=65) PTMC patients is 1.4 times higher than that in the
adult (<65) PTMC patients. The aim of the present study is to identify the
clinical-pathological characteristics and prognostic factors in the elderly PTMC
patients. Methods: The source population is PTMC patients whose information is
available in the Surveillance, Epidemiology and End Results (SEER) database (2004
2013). We analyzed specific selected clinical-pathological parameters and
prognostic factors for the PTMC patients who were aged 65 or above (N=4812).
Results: Within the elderly group, the male patients, in comparison to the
females, had a higher percentage of lymph-node metastases (5.29% vs. 12.27%, P <
0.001), distant metastasis (0.27% vs. 1.07%, P < 0.001), and stage III-IV tumors
(9.19% vs. 15.85%, P < 0.001). Moreover, the elderly patients had a lower median
cause-specific survival (CSS) compared with the adult patients (P < 0.001). Stage
III-IV disease (hazard ratio (HR): 8.064, P < 0.001) was a strong risk factor for
PTMC CSS. Being female (HR: 0.440, P = 0.011), total thyroidectomy (HR: 0.057, P
= 0.001), and lobectomy (HR: 0.058, P < 0.001) were all strong protectors of PTMC
CSS. Conclusion: Thyroidectomy improved CSS of the elderly PTMC patients.
Compared with thyroid lobectomy, total thyroidectomy did not increase CSS for the
elderly PTMC patients. The elderly PTMC patients who received radio therapy did
not experience an increase in CSS.
PMID- 29344272
TI - Cancer vaccine: learning lessons from immune checkpoint inhibitors.
AB - Cancer vaccines have been exclusively studied all through the past decades, and
have made exceptional achievements in cancer treatment. Few cancer vaccines have
been approved by the US Food and Drug Administration (FDA), for instance,
Provenge, which was approved for the treatment of prostate carcinoma in 2012.
Moreover, more recently, T-VEC got approval for the treatment of melanoma. While,
the overall therapeutic effects of cancer vaccines have been taken into
consideration as below expectations, low antigenicity of targeting antigen and
tumor heterogeneity are the two key limiting barriers encountered by the cancer
vaccines. Nonetheless, recent developments in cancer immune-therapies together
with associated technologies, for instance the unparalleled achievements bagged
by immune checkpoint inhibitor based therapies and neo-antigen identification
tools, envisage potential improvements in cancer vaccines in respect to the
treatments of malignancies. This review brings forth measures for the purpose of
refining therapeutic cancer vaccines by learning lessons from the success of PD-1
inhibitor based immune-therapies.
PMID- 29344273
TI - A single nucleotide polymorphism in CYP1B1 leads to differential prostate cancer
risk and telomere length.
AB - BACKGROUND: Cytochrome P450 1B1 (CYP1B1) is a key enzyme in its oestrogen
metabolism pathway, giving rise to hydroxylation and conjugation. Functionally
relevant genetic variants within CYP1B1 may affect the telomere length and
subsequently lead to prostate carcinogenesis. METHODS: We evaluated 8 CYP1B1 tag
single nucleotide polymorphisms (SNPs) in 1015 men with prostate cancer (PCa) and
1052 cancer-free controls, and calculated odds ratios (ORs) and 95% confidence
intervals (CIs) to estimate their association with risk of PCa. The influence of
CYP1B1 SNPs on the relative telomere lengths was then appraised in peripheral
blood leukocytes using real-time PCR. RESULTS:CYP1B1 rs1056836 variant was
associated with decreased risk of PCa [odds ratio (OR): 0.80; 95% confidence
interval (CI): 0.68-0.99, P = 0.041]. Longer telomere length showed a
significantly higher proportion of the CYP1B1 rs1056836 CG/GG genotypes, compared
with that of the CC genotype (OR: 1.60, 95% CI: 1.04-2.45). CONCLUSION: Our
findings suggest that genetic variants within CYP1B1 may confer genetic
susceptibility to PCa by altering telomere length.
PMID- 29344274
TI - Immunotherapy of patient with hepatocellular carcinoma using cytotoxic T
lymphocytes ex vivo activated with tumor antigen-pulsed dendritic cells.
AB - Purpose The aim of this study was to evaluate the clinical response of
immunotherapy with dendritic cell-cytotoxic T lymphocytes (DC-CTLs) in patients
with hepatocellular carcinoma (HCC). Method Sixty-eight patients with a confirmed
diagnosis of HCC and who received follow-up until December 2015 were enrolled. We
measured immune phenotypes of DCs and activated T cells using flow cytometry and
clinical indexes using an electrochemiluminescence method. Results DCs exhibited
up-regulation of the maturation markers CD83, CD80, CD11c, and CD86 on day8.
Levels of IFN-gamma and TNF-alpha were higher in the DCs pulsed with tumor
associated antigens (TAAs) than in DCs with a non-proliferative recombinant
adenovirus. The percentage of regulatory T cells (Tregs) decreased in patients
after DC-CTLs therapy. In addition, serum levels of AFP, AFP-L3, ALT, and CA19-9
were significantly reduced in these patients. Quality of life was improved,
especially on physical functioning scales. Median overall survival (OS) and
progression-free survival (PFS) were 8.2 months and 4.3 months, respectively, for
the control group and 12.8 months and 9 months, respectively, for the DC-CTL
group. Patients treated with DC-CTLs therapy showed a statistically significant
PFS and OS curve (OS: p=0.016; PFS: p<0.0001). In addition, no serious adverse
reactions were observed. Conclusion This study indicated that Tregs, as well as
serum levels of AFP, AFP-L3, ALT, and CA19-9, which were correlated with a poor
prognosis, decreased after DC-CTL treatments. The OS, PFS and the quality of life
of HCC patients partially improved.
PMID- 29344275
TI - Genistein Promotes Proliferation of Human Cervical Cancer Cells Through Estrogen
Receptor-Mediated PI3K/Akt-NF-kappaB Pathway.
AB - Phytoestrogens are polyphenol compounds which have similar structure to 17beta
estradiol (E2), a kind of main estrogen in women. Thus, phytoestrogens may affect
the reproductive and endocrine systems, leading to the development of estrogen
related cancers. The effect of genistein (Gen), one of the most studied
phytoestrogens, on human cervical cancer cells (HeLa) was investigated in this
study. It was found that Gen at concentrations of 0.001, 0.01, 0.1 and 1 umol.L-1
promoted the proliferation of HeLa cells in a dose-dependent manner. Gen
increased the portion of HeLa cells in S phase and decreased the portion of the
cells in G1 phase. Besides, apoptosis rate of the cells was significantly lower
when treated with Gen compared with the control group. It was also found that the
expression of ERalpha, Akt or nuclear NF-kappaB p65 protein was activated by Gen.
The correlation between these three proteins may be as following: ERalpha was the
upstream, followed by Akt, and then nuclear NF-kappaB p65 protein. In addition,
the downstream genes of activated nuclear NF-kappaB p65 were found to be
associated with cell cycle and apoptosis of cancer cells. Our results suggested
that Gen may stimulate cell proliferation partially through the estrogen receptor
mediated PI3K/Akt-NF-kappaB pathway and the further activation of the downstream
genes of nuclear NF-kappaB p65.
PMID- 29344276
TI - The Clinicopathological Features and Survival Outcomes of Different Histological
Subtypes in Triple-negative Breast Cancer.
AB - Purpose: To determine the clinicopathological features and survival outcomes of
triple-negative breast cancer (TNBC) according to different histological
subtypes. Methods: Using the Surveillance, Epidemiology, and End Results
database, we included TNBC cases in 2010-2013. The effect of histological subtype
on breast cancer-specific survival (BCSS) and overall survival (OS) were analyzed
using univariate and multivariate analyses. Results: A total of 19,900 patients
were identified. Infiltrating ductal carcinoma not otherwise specified accounted
for 91.6% of patients, followed by metaplastic carcinoma (2.7%), medullary
carcinoma (1.4%), mixed lobular-ductal carcinoma (1.4%), lobular carcinoma
(1.3%), apocrine carcinoma (1.0%), and adenoid cystic carcinoma (0.6%). Medullary
carcinoma was more frequently poorly/undifferentiated. Significantly more lobular
carcinoma, mixed lobular-ductal carcinoma, and metaplastic carcinoma patients had
larger tumors. Adenoid cystic carcinoma, metaplastic carcinoma, medullary
carcinoma, and apocrine carcinoma were more frequently node-negative. Lobular
carcinoma (16.0%) and mixed lobular-ductal carcinoma (10.4%) more frequently had
distant stage at initial diagnosis. Histologic subtype was an independent
prognostic factor of BCSS and OS. Compared with infiltrating ductal carcinoma,
medullary carcinoma and apocrine carcinoma had better BCSS and OS, while mixed
lobular-ductal carcinoma and metaplastic carcinoma had worse survival. Adenoid
cystic carcinoma survival was not significantly different from that of
infiltrating ductal carcinoma. Conclusions: TNBC histological subtypes have
different clinicopathological characteristics and survival outcomes. Medullary
carcinoma and apocrine adenocarcinoma have excellent prognosis; mixed lobular
ductal carcinoma and metaplastic carcinoma are the most aggressive subtypes.
PMID- 29344277
TI - Capn4 overexpression indicates poor prognosis of ovarian cancer patients.
AB - Recent studies have shown a close correlation between Capn4 expression and the
prognosis of patients with solid tumors. This study aimed to investigate clinical
role of Capn4 in ovarian cancer. The expression of Capn4 in 113 ovarian cancer
and 35 non-tumor tissue samples were detected by quantitative real-time
polymerase chain reaction (qRT-PCR). Capn4 expression was significantly
upregulated in ovarian cancer tissues compared with non-tumor tissues (p < 0.01),
and was positively correlated to FIGO stage, tumor grade and distant metastasis
of ovarian cancer. Kaplan-Meier analysis indicated that patients with high Capn4
expression had shorter overall survival (HR = 1.929, 95%CI: 1.210-3.077, P=
0.006) and progress-free survival (PFS) (HR = 2.043, 95%CI: 1.276-3.271, P=
0.003). Moreover, univariate Cox regression analysis demonstrated that Capn4
overexpression was an unfavorable prognostic factor for ovarian cancer (HR =
2.819, 95%CI: 1.365-3.645, P = 0.003). After the adjustment with age,
histological type and tumor size, multivariate Cox regression analysis showed
that Capn4 expression level (HR = 2.157,95%CI: 1.091-3.138, P = 0.014), distant
metastasis (HR = 1.576, 95%CI: 1.025-3.012, P = 0.028), tumor grade (HR = 1.408,
95%CI: 0.687-2.884, P = 0.037), and FIGO stage (HR = 1.791, 95%CI: 1.016-3.158,
P=0.036) were independent poor prognostic indicators for ovarian cancer. In
conclusion, Capn4 has the potential as a new prognostic marker for patients with
ovarian cancer.
PMID- 29344278
TI - Potent peptide-conjugated silicon phthalocyanines for tumor photodynamic therapy.
AB - Phthalocyanines (Pcs) are a group of promising photosensitizers for use in
photodynamic therapy (PDT). However, their extremely low solubility and their
strong tendency to aggregate in aqueous solution greatly restrict their
application. Conjugation of Pc macrocycles with peptide ligands could be a very
useful strategy to optimize the physical properties of Pcs not only by increasing
their water solubility and reducing their aggregation but also by endowing the
conjugates with a tumor-targeting capability. To develop highly potent
photosensitizers for tumor PDT, we prepared new peptide-conjugated
photosensitizers using silicon Pc (SiPc), which has much higher photodynamic
activity than zinc Pcs, as the light activation moiety and the cRGDfK peptide (or
simply cRGD) as the peptide moiety. A polyethylene glycol linker and an extra
carboxylic acid group were also tested for introduction into the conjugates to
optimize the conjugate structure. The conjugates' photophysical and photodynamic
behaviors were then carefully evaluated and compared using in vitro and in vivo
experiments. One of the prepared conjugates, RGD-(Linker)2-Glu-SiPc, showed
excellent physical properties and photodynamic activity, with an EC50 (half
maximal effective concentration) of 10-20 nM toward various cancer cells. This
conjugate eradicated human glioblastoma U87-MG tumors in a xenograft murine tumor
model after only one dose of photodynamic treatment, with no tumor regrowth
during observation for up to 35 days. The conjugate RGD-(Linker)2-Glu-SiPc thus
showed highly promising potential for use in tumor treatment.
PMID- 29344279
TI - Positive Expression of SMYD2 is Associated with Poor Prognosis in Patients with
Primary Hepatocellular Carcinoma.
AB - Purpose: SET and MYND domain-containing protein2 (SMYD2), a histone lysine
methyltransferases, is a candidate human oncogene in multiple tumors. However,
the expression dynamics of SMYD2 in hepatocellular carcinoma (HCC) and its
clinical/prognostic significance are unclear. Methods: The SMYD2 expression
profile was examined by quantitative real-time polymerase chain reaction (qRT
PCR), and immunohistochemistry (IHC) in HCC tissues and matched adjacent non
tumorous tissues. SMYD2 was silenced in HCC cell lines to determine its role in
tumor proliferation and cell cycle progression, and the possible mechanism.
Spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards
regression model were used to analyze the data. Results: The SMYD2 expression in
HCC tissues were significantly up-regulated at both mRNA and protein levels as
compared with the matched adjacent non-tumorous tissues. By IHC, positive
expression of SMYD2 was examined in 122/163 (74.85%) of HCC and in 10/59 (16.95%)
of tumor-adjacent tissues. Positive expression of SMYD2 was correlated with tumor
size, vascular invasion, differentiation and TNM stage (P < 0.05). In univariate
survival analysis, a significant association between positive expression of SMYD2
and shortened patients' survival was found (P < 0.05). Importantly, SMYD2
expression together with vascular invasion (P < 0.05) provided significant
independent prognostic parameters in multivariate analysis. Functionally, SMYD2
silenced markedly inhibited cell proliferation and cell cycle progression in SMMC
7721 cell. Conclusions: Our findings provide evidences that positive expression
of SMYD2 in HCC may be important in the acquisition of an aggressive phenotype,
and it is an independent biomarker for poor prognosis of patients with HCC.
PMID- 29344280
TI - MiR-378 and MiR-1827 Regulate Tumor Invasion, Migration and Angiogenesis in Human
Lung Adenocarcinoma by Targeting RBX1 and CRKL, Respectively.
AB - MicroRNAs (miRNAs) have been extensively studied over the decades and have been
proposed as potential molecular targets for cancer treatment. Studies have shown
that miR-378 participates in numerous biological processes in various cancers;
whereas miR-1827 has only been reported in pediatric glioma. The mechanism of how
miRNAs modulate lung cancer metastasis remains unclear. Our previous study
demonstrated that miR-378 is up-regulated while miR-1827 is down-regulated in
high invasive lung cancer sub-cell lines, and their biological functions have
been described. Here, we report that miR-378 and miR-1827 modulate lung cancer
cell invasion and migration via epithelial-mesenchymal transition (EMT). We also
demonstrated that cells treated with miR-378 inhibitors or miR-1827 mimics had
reduced number of metastases and ectopic vessels in the zebrafish embryo model.
We then showed that miR-378 promoted invasion and miR-1827 suppressed migration
by targeting RBX1 and CRKL, respectively. Restored protein expression in miRNA
overexpressed/ miRNA-suppressed cells attenuated the inhibitory/ inducing effect
of the miRNA on lung cancer cells. Collectively, our findings highlight that miR
378 and miR-1827 could serve as novel therapeutic targets in lung cancer.
PMID- 29344281
TI - Keratin17 Promotes Tumor Growth and is Associated with Poor Prognosis in Gastric
Cancer.
AB - Krt17 is a 48kDa protein member of keratin family. Previous literatures have
demonstrated Krt17 may play a promotive role in the progression of various
malignancies. However, the exact function of Krt17 in the carcinogenesis and the
progression of gastric cancer (GC) remains unknown. In the present study, the
expression of Krt17 in 20 fresh GC and matched normal tissues were detected and
Krt17 was found to be significantly increased in GC tissues compared to normal
tissues. And then the immunochemistry was performed to investigate the Krt17
expression in 569 GC tissue specimens, we found that the expression of Krt17 was
remarkably positively correlated with the tumor size (P < 0.01), depth of
invasion (T) (P < 0.001), lymph node metastasis (N) (P < 0.001), tumor node
metastasis (TNM) stage (P < 0.001) and vascular invasion (P < 0.05). High
expression of Krt17 predicted a poor prognosis of GC patients. In addition, we
showed silencing of Krt17 inhibited GC cell proliferation, migration and
invasion, and induced cell apoptosis by altering Bcl2 family protein expression
and cleaved caspase3 upregulation. Moreover, silencing of Krt17 led to cell cycle
arrest at G1/S stage by decreasing cyclin E1 and cyclin D expression. In
conclusion, our findings revealed Krt17 can be used as a novel predictive
biomarker, thus providing a novel therapeutic target for GC patients.
PMID- 29344282
TI - Clinical Significance of Glycoprotein Non-metastatic B and Its Association with
EGFR/HER2 in Gastrointestinal Cancer.
AB - Glycoprotein non-metastatic B (GPNMB), a type I transmembrane glycoprotein, is
overexpressed in melanoma and breast cancer and promotes cancer-cell invasion and
motility. We previously reported cross-talk between GPNMB and human epidermal
growth factor receptor 2 (HER2) in breast cancer, suggesting that GPNMB might
play an important role in resistance to anti-HER2 therapy in breast cancer. Here,
we clarified the association between GPNMB and HER-family proteins in
gastrointestinal cancer by examining their relationships using gastric and
colorectal cancer cell lines. We found that GPNMB depletion of by small
interfering RNA increased epidermal growth factor receptor (EGFR) expression and
phosphorylation through AKT8 virus oncogene cellular homolog (AKT) and mitogen
activated protein kinase (MAPK) pathways. Additionally, treatment with cetuximab
(CTX) also increased GPNMB expression, and combination therapy consisting of
GPNMB depletion and CTX treatment significantly suppressed cell growth in
colorectal cancer cell lines, but not in gastric cancer cell lines. Furthermore,
we also evaluated changes in GPNMB expression in vivo, with immunohistochemistry
detecting GPNMB overexpression in a colorectal cancer patient following anti-EGFR
therapy. These results suggested possible cross-talk between GPNMB and EGFR, and
that GPNMB might play an important role in resistance to anti-EGFR therapy in
gastrointestinal cancer.
PMID- 29344283
TI - Antigen presentation of the Oct4 and Sox2 peptides by CD154-activated B
lymphocytes enhances the killing effect of cytotoxic T lymphocytes on tumor stem
like cells derived from cisplatin-resistant lung cancer cells.
AB - The present study investigated whether antigen presentation of the Oct4 and Sox2
peptides by CD154-activated B lymphocytes can enhance the killing effect of CD8+
cytotoxic T lymphocytes (CTLs) on lung stem-like cancer cells (SLCCs). The CTLs
were generated using an accelerated co-cultured dendritic cells (DC) (acDC) assay
by incubating human peripheral blood mononuclear cells (PBMCs) from non-small
cell lung cancer patients with antigen peptides of Oct4 and Sox2 in the presence
of several DC-activating agents. CD154+ NIH3T3 cells prepared by CD154 lentiviral
transfection were used as feeder layer to activate primary B cells (CD19+)
obtained from PBMCs. Activated B cells were co-cultured with CTLs to present
antigen peptides of Oct4 and Sox2. CTLs co-cultured with activated B cells were
evaluated for the levels of secreted inflammatory cytokines using ELISA. In
addition, the killing effect of the CTLs on SLCCs derived from cisplatin
resistant strain of human lung cancer cell line PC9 was evaluated by flow
cytometry using CFSE labeling of the target cells. After the acDC assay, the
PBMCs exhibited a significant (p<0.01) increase in the population of CD8+/CD3+
cells, indicating successful preparation of CTLs. The primary B cells cultured on
the CD154+ NIH3T3 feeder layer resulted in significant (p<0.01) increase in the
proportions of population expressing CD80, CD86, or HLA-A, indicating successful
activation of the B cells. The co-culture of CTLs with CD154-activated B cells
presenting the Oct4 and Sox2 peptides caused significant increase in the levels
of secretory inflammatory cytokines and exhibited enhanced killing of the SLCCs
derived from cisplatin-resistant PC9 cells. Antigen presentation of the Oct4 and
Sox2 peptides by CD154-activated B cells can enhance the killing effect of CTLs
towards lung SLCCs.
PMID- 29344285
TI - Long noncoding RNA H19 derived miR-675 regulates cell proliferation by down
regulating E2F-1 in human pancreatic ductal adenocarcinoma.
AB - The long noncoding RNA (lncRNA) H19 has been proven to be overexpressed in human
pancreatic ductal adenocarcinoma (PDAC). H19-induced PDAC cell proliferation is
cell cycle-dependent by modulating E2F-1. However, the mechanism of how H19
regulates E2F-1 remains unclear. In this study, we investigated the expression of
miR-675 in PDAC tumours and cells, the biological function of miR-675 in PDAC
cell proliferation and the possible relationship among H19, miR-675 and E2F-1. As
a transcript of the first exon of H19, the level of miR-675 was negatively
correlated with H19 expression in microdissected PDAC tissues (r=-0.0646,
P=0.001). The serum miR-675 expression was significantly down-regulated in
patients with PDAC compared to those in healthy individuals. Moreover, an
evaluation of five PDAC cases showed that there was a remarkable increase of
serum miR-675 levels after resection of the primary tumours. Ectopic
overexpression of miR-675 in AsPC-1 and PANC-1 cells decreased cell viability,
the colony-forming ability and the percentage of cells in S phase; contrarily,
miR-675 knockdown resulted in enhanced cell proliferation. Furthermore, the
suppressed cell proliferation caused by H19 knockdown could be rescued by
inhibiting miR-675 expression. Additionally, intratumoural injection of either
miR-675 agomir or antagomir could significantly affect tumour growth in vivo.
Both the bioinformatic prediction and luciferase activity assay confirmed that
E2F-1 was a direct target of miR-675. And the decrease of E2F-1 protein
expression caused by siH19 could be partially reversed by miR-675 knockdown. We
concluded that there might be a H19/miR-675/E2F-1 regulatory loop in cell cycle
modulation. Serum miR-675 might serve as a potential biomarker for not only early
diagnosis but also outcome prediction in PDAC.
PMID- 29344284
TI - miR-149 in Human Cancer: A Systemic Review.
AB - MicroRNAs (miRNAs) are small noncoding RNAs that regulate post-transcriptional
gene expression via binding to the 3'-untranslated region (3'-UTR) of targeted
mRNAs. They are reported to play important roles in tumorigenesis and progression
of various cancers. Among them, miR-149 was confirmed to be aberrantly regulated
in various tumors. In this review, we provide a complex overview of miR-149,
particularly summarize the critical roles of it in cancers and expect to lay the
foundation for future works on this important microRNA.
PMID- 29344286
TI - Identification of Biomarker for Cutaneous Squamous Cell Carcinoma Using
Microarray Data Analysis.
AB - Cutaneous squamous cell carcinoma (CSCC) is one of the most malignant tumors
worldwide. We aimed to explore the molecular mechanism of this CSCC and screen
feature genes that can function as the biomarker of CSCC and thus provide a
theoretical basis for the pathogenesis research and development of medicine. The
method of microarray data analysis was used in this study to explore the
differentially expressed genes between tissues of normal specimens and tissues of
patients with CSCC. Besides, functional enrichment analysis and signal pathway
were performed on these genes to screen the feature genes that are closely
associated with CSCC can function as the potential biomarkers of CSCC.A total of
53 samples from two datasets, GSE45216 and GSE45164, were used in the
differentially expressed analysis. And as a result, a total of 833 genes were
screened out, including 465 up-regulated genes and 215 down-regulated genes.
Candidate genes, including up-regulated genes like S100A12, MMP1, DEFB4B/DEFB4A,
KRT16 and PI3, and down-regulated genes like EGR3, LRP4, C14orf132, PAMR1, CCL27,
and KRT2 were screened out. All these genes were testified in the dataset of
GSE66359. The result showed that only three genes, KRT16, PI3 and EGR3, were
mostly differentially expressed and only EGR3 had the same expression pattern
with both datasets, GSE45216 and GSE45164.Of note, EGR3 gene was found to be the
most differentially expressed gene in cutaneous squamous cell carcinoma, which
had the potential to function as the candidate genes and help in the diagnosis
and prognostic treatments of CSCC.
PMID- 29344287
TI - Role of miR-483 in digestive tract cancers: from basic research to clinical
value.
AB - Digestive tract cancers (DTCs) is the most common malignant tumors in the world.
Despite surgery and medical technology have witnessed the increasing development
and sharp advancement in the past decade, DTCs remain a critical concern with
high morbidity and mortality. Since a class of small noncoding RNAs termed miRNAs
were identified several years ago, increasing studies have attempted to
illustrate the relationship between the specific miRNAs dysregulated expression
levels and the diseases phenotypic changes. For example, microRNA-483 (miR-483)
aberrant expression plays a pivotal part in tumor biology in a variety of human
cancer, including DTCs. In this review, we focus on the present key findings from
recent profiling studies, discuss the use of miR-483 as a novel biomarker for
DTCs. At the same time, we emphasize the significant diversities and technical
difficulties must be overcome before clinically relevant signatures arose. It is
believed that this might provide researchers an insight into the molecular
targeting cancer treatment.
PMID- 29344288
TI - GP73 level determines chemotherapeutic resistance in human hepatocellular
carcinoma cells.
AB - Objective GP73 is a new hepatocellular carcinoma (HCC) marker, which is highly
expressed in hepatocellular carcinoma and closely relates to prognosis. This
study was to investigate the effects of GP73 on cellular proliferation,
apoptosis, oxaliplatin (OXA) resistance and secretory clusterin (sCLU) of HCC
cells. Materials and Methods Western blot and immunofluorescence was used to
detect the expression of GP73 in 8 types of commonly used HCC cell lines. Drug
resistance was induced by increasing concentration gradient method. The drug
resistant human HCC cell lines underwent GP73 overexpression or inhibition. Flow
cytometry were used to detect the proliferation and apoptosis of HCC cell lines.
The changes of sCLU were detected by enzyme-linked immunosorbent assay (ELISA).
Results The expression of GP73 in MHC-97H cells was the highest and in Hep3B
cells the lowest. The expression of GP73 was found further elevated in OXA
resistant MHC-97H cells. After the knockdown of GP73 in OXA-resistant 97H cells,
the IC50 of OXA decreased and the ability of cell proliferation decreased
significantly. After over-expression of GP73 in OXA-resistant Hep3B cells, the
IC50 of OXA increased and the cell proliferation ability increased, showing that
GP73 is critical for OXA resistant in HCC cell lines; No significant change of
sCLU level in GP73 overexpressed Hep3B and GP73 blocked MHCC-97H were identified.
Conclusion The expression level of GP73 is critical for the resistance of OXA in
HCC cell lines.
PMID- 29344289
TI - Limb-bud and Heart Overexpression Inhibits the Proliferation and Migration of
PC3M Cells.
AB - Background: The limb-bud and heart gene (LBH) was discovered in the early 21st
century and is specifically expressed in the mouse embryonic limb and heart
development. Increasing evidences have indicated that LBH not only plays an
important role in embryo development, it is also closely correlated with the
occurance and progression of many tumors. However, its function in prostate
cancer (PCa) is still not well understood. Here, we explored the effects of LBH
on the proliferation and migration of the PCa cell line PC3M. Methods: LBH
expression in tissues and cell lines of PCa was detected by immunohistochemistry
and Western blotting. Lentivirus was used to transduct the LBH gene into the PC3M
cells. Stable LBH-overexpressing PC3M-LBH cells and PC3M-NC control cells were
obtained via puromycin screening. Cell proliferation was examined using the 3
(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cell
cycle distribution and apoptosis rate were investigated using flow cytometry.
Cell migration was studied using the Transwell assay. Results: LBH expression
level was down-regulated in 3 different PCa cell lines, especially in PC3M cells,
compared with the normal prostate epithelial cells(RWPE-1). Cell lines of LBH
upregulated PC3M-LBH and PC3M-NC control were successfully constructed.
Significantly increased LBH expression level and decreased cyclin D1 and cyclin
E2 expression level was found in PC3M-LBH cells as compared to the PC3M-NC cells.
The overexpression of LBH significantly inhibited PC3M cell proliferation in
vitro and tumor growth in nude mice. LBH overexpression in PC3M cell, also
induced cell cycle G0/G1 phase arrest and decreased the migration of PC3M cells.
Conclusions: Our results reveal that LBH expression is down-regulated in the
tissue and cell lines of PCa. LBH overexpression inhibits PC3M cell proliferation
and tumor growth by inducing cell cycle arrest through down-regulating cyclin
D1and cyclin E2 expression. LBH might be a therapeutic target and potential
diagnostic marker in PCa.
PMID- 29344290
TI - Prophylactic cranial irradiation in resected small cell lung cancer: A systematic
review with meta-analysis.
AB - Background: The use of PCI in early operable patients with small cell lung cancer
(SCLC) is still controversial. Therefore, we conducted a systematic review with
meta-analysis to investigate the effects of PCI in resected SCLC patients.
Methods: Relevant studies were identified from PubMed and EMBASE databases, the
pooled hazard risks were obtained by the random-effects model. We also analyzed
the brain metastasis (BM) risk in p-stage I patients without PCI. Results: Five
retrospective studies were identified and a total of 1691 patients were included
in our analysis, 315 of them received PCI. For all the resected patients, PCI was
associated with improved overall survival (HR: 0.52, 95% CI: 0.33-0.82), and
reduced brain metastasis risk (RR: 0.50, 95%CI: 0.32-0.78). However, with regard
to p-stage I patients, no survival benefit was brought by PCI (HR: 0.87, 95% CI:
0.34-2.24). Moreover, the pooled analysis of 7 studies found that the 5-year
brain metastasis risk was relatively low (12%, 95% CI: 8%-17%) for p-stage I
patients without PCI. Conclusions: PCI might be associated with a favorable
survival advantage and reduced BM risk in complete resected SCLC patients, except
for p-stage I patients.
PMID- 29344291
TI - In Vivo Double Targeting of C26 Colon Carcinoma Cells and Microenvironmental
Protumor Processes Using Liposomal Simvastatin.
AB - Purpose: Besides cholesterol lowering effects, simvastatin (SIM) at very high
doses possesses antitumor actions. Moreover our previous studies demonstrated
that tumor-targeted delivery of SIM by using long-circulating liposomes (LCL)
improved the therapeutic index of this drug in murine melanoma-bearing mice. To
evaluate whether this finding can be exploited for future therapy of colorectal
cancer the antitumor activity and the underlying mechanisms of long-circulating
liposomal simvastatin (LCL-SIM) efficacy for inhibition of C26 murine colon
carcinoma growth in vivo were investigated. Materials and Methods: To find LCL
SIM dose with the highest therapeutic index, dose-response relationship and side
effects of different LCL-SIM doses were assessed in C26 colon carcinoma-bearing
mice. The underlying mechanisms of LCL-SIM versus free SIM treatments were
investigated with regard to their actions on C26 cell proliferation and apoptosis
(via tumor tissues immunostaining for PCNA and Bax markers), tumor inflammation
(via western blot analysis of NF-kappaBeta production), angiogenesis (using an
angiogenic protein array), and oxidative stress (by HPLC assessment of
malondialdehyde). Results: Our findings suggest that LCL-SIM antitumor activity
on C26 colon carcinoma is a result of the tumor-targeting property of the
liposome formulation, as free SIM treatment was ineffective. Moreover, LCL-SIM
exerted significant antiproliferative and pro-apoptotic actions on C26 cells,
notable suppressive effects on two main supportive processes for tumor
development, inflammation and angiogenesis, and only slight anti-oxidant actions.
Conclusion: Our data proved that LCL-SIM antitumor activity in C26 colon
carcinoma was based on cytotoxic effects on these cancer cells and suppressive
actions on tumor angiogenesis and inflammation.
PMID- 29344293
TI - Ligand Activation of PPARgamma by Ligustrazine Suppresses Pericyte Functions of
Hepatic Stellate Cells via SMRT-Mediated Transrepression of HIF-1alpha.
AB - Rationale: Hepatic stellate cells (HSCs) are liver-specific pericytes regulating
vascular remodeling during hepatic fibrosis. Here, we investigated how
ligustrazine affects HSC pericyte functions. Methods: Rat HSC-T6 and human HSC
LX2 cells were cultured, and multiple molecular experiments including real-time
PCR, Western blot, flow cytometry, immunofluorescence, electrophoretic mobility
shift assay and co-immunoprecipitation were used to elucidate the underlying
mechanisms. Molecular simulation and site-directed mutagenesis were performed to
uncover the target molecule of ligustrazine. Rats were intoxicated with CCl4 for
evaluating ligustrazine's effects in vivo. Results: Ligustrazine inhibited
angiogenic cytokine production, migration, adhesion and contraction in HSCs, and
activated PPARgamma. Selective PPARgamma inhibitor GW9662 potently abrogated
ligustrazine suppression of HSC pericyte functions. Additionally, HIF-1alpha
inhibitor PX-478 repressed HSC pericyte functions, and ligustrazine inhibited the
transcription of HIF-1alpha, which was diminished by GW9662. Moreover,
ligustrazine downregulation of HIF-1alpha was rescued by knockdown of SMRT, and
ligustrazine increased PPARgamma physical interaction with SMRT, which was
abolished by GW9662. These findings collectively indicated that activation of
PPARgamma by ligustrazine led to transrepression of HIF-1alpha via a SMRT
dependent mechanism. Furthermore, molecular docking evidence revealed that
ligustrazine bound to PPARgamma in a unique double-molecule manner via hydrogen
bonding with the residues Ser289 and Ser342. Site-directed mutation of Ser289
and/or Ser342 resulted in the loss of ligustrazine transrepression of HIF-1alpha
in HSCs, indicating that interactions with both the residues were indispensable
for ligustrazine effects. Finally, ligustrazine improved hepatic injury,
angiogenesis and vascular remodeling in CCl4-induced liver fibrosis in rats.
Conclusions: We discovered a novel ligand activation pattern for PPARgamma
transrepression of the target gene with therapeutic implications in HSC pericyte
biology and liver fibrosis.
PMID- 29344292
TI - Galectin-3 Activation and Inhibition in Heart Failure and Cardiovascular Disease:
An Update.
AB - Galectin-3 is a versatile protein orchestrating several physiological and
pathophysiological processes in the human body. In the last decade, considerable
interest in galectin-3 has emerged because of its potential role as a biotarget.
Galectin-3 is differentially expressed depending on the tissue type, however its
expression can be induced under conditions of tissue injury or stress. Galectin-3
overexpression and secretion is associated with several diseases and is
extensively studied in the context of fibrosis, heart failure, atherosclerosis
and diabetes mellitus. Monomeric (extracellular) galectin-3 usually undergoes
further "activation" which significantly broadens the spectrum of biological
activity mainly by modifying its carbohydrate-binding properties. Self
interactions of this protein appear to play a crucial role in regulating the
extracellular activities of this protein, however there is limited and
controversial data on the mechanisms involved. We therefore summarize (recent)
literature in this area and describe galectin-3 from a binding perspective
providing novel insights into mechanisms by which galectin-3 is known to be
"activated" and how such activation may be regulated in pathophysiological
scenarios.
PMID- 29344295
TI - Peptide receptor radionuclide therapy as a new tool in treatment-refractory
sarcoidosis - initial experience in two patients.
AB - Sarcoidosis is a multisystem granulomatous disorder of unknown etiology that can
involve virtually all organ systems. Whereas most patients present without
symptoms, progressive and disabling organ failure can occur in up to 10% of
subjects. Somatostatin receptor (SSTR)-directed peptide receptor radionuclide
therapy (PRRT) has recently received market authorization for treatment of SSTR
positive neuroendocrine tumors. Methods: We describe the first case series
comprising two patients with refractory multi-organ involvement of sarcoidosis
who received 4 cycles of PRRT. Results: PRRT was well-tolerated without any acute
adverse effects. No relevant toxicities could be recorded during follow-up.
Therapy resulted in partial response accompanied by a pronounced reduction in
pain (patient #1) and stable disease regarding morphology as well as disease
activity (patient #2), respectively. Conclusion: Peptide receptor radionuclide
therapy in sarcoidosis is feasible and might be a new valuable tool in patients
with otherwise treatment-refractory disease. Given the long experience with and
good tolerability of PRRT, further evaluation of this new treatment option for
otherwise treatment-refractory sarcoidosis in larger patient cohorts is
warranted.
PMID- 29344294
TI - Cardiomyocyte-Restricted Low Density Lipoprotein Receptor-Related Protein 6
(LRP6) Deletion Leads to Lethal Dilated Cardiomyopathy Partly Through Drp1
Signaling.
AB - Low density lipoprotein receptor-related protein 6 (LRP6), a wnt co-receptor,
regulates multiple functions in various organs. However, the roles of LRP6 in the
adult heart are not well understood. Methods: We observed LRP6 expression in
heart with end-stage dilated cardiomyopathy (DCM) by western blot. Tamoxifen
inducible cardiac-specific LRP6 knockout mouse was constructed. Hemodynamic and
echocardiographic analyses were performed to these mice. Results: Cardiac LRP6
expression was dramatically decreased in patients with end-stage dilated
cardiomyopathy (DCM) compared to control group. Tamoxifen-inducible cardiac
specific LRP6 knockout mice developed acute heart failure and mitochondrial
dysfunction with reduced survival. Proteomic analysis suggests the fatty acid
metabolism disorder involving peroxisome proliferator-activated receptors (PPARs)
signaling in the LRP6 deficient heart. Accumulation of mitochondrial targeting to
autophagosomes and lipid droplet were observed in LRP6 deletion hearts. Further
analysis revealed cardiac LRP6 deletion suppressed autophagic degradation and
fatty acid utilization, coinciding with activation of dynamin-related protein 1
(Drp1) and downregulation of nuclear TFEB (Transcription factor EB). Injection of
Mdivi-1, a Drp1 inhibitor, not only promoted nuclear translocation of TFEB, but
also partially rescued autophagic degradation, improved PPARs signaling, and
attenuated cardiac dysfunction induced by cardiac specific LRP6 deletion.
Conclusions: Cardiac LRP6 deficiency greatly suppressed autophagic degradation
and fatty acid utilization, and subsequently leads to lethal dilated
cardiomyopathy and cardiac dysfunction through activation of Drp1 signaling. It
suggests that heart failure progression may be attenuated by therapeutic
modulation of LRP6 expression.
PMID- 29344296
TI - CDK16 Phosphorylates and Degrades p53 to Promote Radioresistance and Predicts
Prognosis in Lung Cancer.
AB - Rationale: Radioresistance is considered the main cause of local relapse in lung
cancer. However, the molecular mechanisms of radioresistance remain poorly
understood. This study investigates the role of CDK16 in radioresistance of human
lung cancer cells. Methods: The expression levels of CDK16 were determined by
immunohistochemistry in lung cancer tissues and adjacent normal lung tissues.
Immunoprecipitation assay and GST pulldown were utilized to detect the protein
protein interaction. The phosphorylation of p53 was evaluated by in vitro kinase
assay. Poly-ubiquitination of p53 was examined by in vivo ubiquitination assay.
Cell growth and apoptosis, ROS levels and DNA damage response were measured for
functional analyses. Results: We showed that CDK16 is frequently overexpressed in
lung cancer cells and tissues, and high levels of CDK16 are correlated with lymph
node stage and poor prognosis in lung cancer patients. Furthermore, we provided
evidence that CDK16 binds to and phosphorylates p53 at Ser315 site to inhibit
transcriptional activity of p53. Moreover, we uncovered that this phosphorylation
modification accelerates p53 degradation via the ubiquitin/proteasome pathway.
Importantly, we demonstrated that CDK16 promotes radioresistance by suppressing
apoptosis and ROS production as well as inhibiting DNA damage response in lung
cancer cells in a p53-dependent manner. Conclusion: Our findings suggest that
CDK16 negatively modulates p53 signaling pathway to promote radioresistance, and
therefore represents a promising therapeutic target for lung cancer radiotherapy.
PMID- 29344297
TI - Mesoporous Carbon Nanospheres as a Multifunctional Carrier for Cancer
Theranostics.
AB - Optical nanomaterials with intense absorption in near-infrared (NIR) region hold
great promise for biomedical applications such as photothermal therapy (PTT) and
photoacoustic imaging (PAI). In this work, we report mesoporous carbon
nanospheres (Meso-CNs) with broadband and intense absorption in the UV-Vis-NIR
region (300-1400 nm) and explore their potential as a multifunctional platform
for photoacoustic imaging and chemo-photothermal therapy. Methods: Meso-CNs were
prepared by a "silica-assisted" synthesis strategy and characterized by
transmission electron microscope and optical spectroscopy. We investigated the
photothermal conversion and photoacoustic imaging of Meso-CNs in comparison with
single-walled carbon nanotubes (SWCNTs), graphene and gold nanorods (GNRs). In
vitro cellular assays and in vivo chemo-photothermal combination therapy were
performed. Results: The absorption coefficients of Meso-CNs are 1.5-2 times
higher than those of SWCNTs and graphene and are comparable to those of GNRs in
both the first and the second near-infrared optical windows (NIR-I and NIR-II) of
tissues. When exposed to an NIR laser, the photothermal and photoacoustic signal
generation of Meso-CNs are also stronger than those of SWCNTs, graphene, and
GNRs. DOX was loaded into Meso-CNs with a high efficiency (35 wt%) owing to the
unique mesoporous structure. Particularly, the drug release from Meso-CNs is
sensitive to both pH and NIR light stimulation. In vivo chemo-photothermal
combination therapy demonstrates a remarkable inhibition effect on tumor growth
under NIR laser treatment. Conclusions: We have developed Meso-CNs for
photothermal conversion and photoacoustic imaging. The porous structure also
serves as a drug carrier and the drug release can be controlled by pH and
external light. The high drug loading capacity, superior photothermal and
photoacoustic generation, together with the apparent chemo-photothermal
therapeutic effect, make Meso-CNs a promising platform for cancer theranostics.
PMID- 29344298
TI - AKR1C1 Activates STAT3 to Promote the Metastasis of Non-Small Cell Lung Cancer.
AB - Metastasis is the leading cause of mortality for human non-small cell lung cancer
(NSCLC). However, it is difficult to target tumor metastasis because the
molecular mechanisms underlying NSCLC invasion and migration remain unclear.
Methods: GEO data analyses and IHC analyses were performed to identify that the
expression level of AKR1C1, a member of human aldo-keto reductase family, was
highly elevated in patients with metastasis or metastatic foci of NSCLC patients.
Functional analyses (in vitro and in vivo) and quantitative genomic analyses were
preformed to confirm the pro-metastatic effects of AKR1C1 and the underlying
mechanisms. The correlation of AKR1C1 with the prognosis of NSCLC patients was
evaluated using Kaplan-Meier analyses. Results: in NSCLC patients, AKR1C1
expression was closely correlated with the metastatic potential of tumors. AKR1C1
overexpression in nonmetastatic cancer cells significantly promoted metastasis
both in vitro and in vivo, whereas depletion of AKR1C1 in highly metastatic
tumors potently alleviated these effects. Quantitative genomic and functional
analyses revealed that AKR1C1 directly interacted with STAT3 and facilitated its
phosphorylation-thus reinforcing the binding of STAT3 to the promoter regions of
target genes-and then transactivated these genes, which ultimately promoted tumor
metastasis. Further studies showed that AKR1C1 might facilitate the interaction
of STAT3 with its upstream kinase JAK2. Intriguingly, AKR1C1 exerted these pro
metastatic effects in a catalytic-independent manner. In addition, a significant
correlation between AKR1C1 and STAT3 pathway was observed in the metastatic foci
of NSCLC patients, and the AKR1C1-STAT3 levels were highly correlated with a poor
prognosis in NSCLC patients. Conclusions: taken together, we show that AKR1C1 is
a potent inducer of NSCLC metastasis. Our study uncovers the active function of
AKR1C1 as a key component of the STAT3 pathway, which promotes lung cancer
metastasis, and highlights a candidate therapeutic target to potentially improve
the survival of NSCLC patients with metastatic disease.
PMID- 29344299
TI - Enhanced Synergism of Thermo-chemotherapy For Liver Cancer with Magnetothermally
Responsive Nanocarriers.
AB - A combination of magnetic hyperthermia and magnetothermally-facilitated drug
release system was developed as a promising strategy for liver cancer therapy.
The thermosensitive copolymer, 6sPCL-b-P(MEO2MA-co-OEGMA) shows a good
temperature-controlled drug release response. Mn-Zn ferrite magnetic
nanoparticles (MZF-MNPs) exhibit a strong magnetic thermal effect with an
alternating magnetic field (AMF). Owing to its high magnetic sensitivity, the
magnetothermally-responsive nanocarrier/doxorubicin (MTRN/DOX) can be
concentrated in the tumor site efficiently through magnetic targeting. Given this
information, we synthesized MTRN/DOX which was composed of MZF-MNPs,
thermosensitive copolymer drug carriers, and the chemotherapeutic drug---DOX, to
study its anticancer effects both in vitro and in vivo.METHODS: MTRN/DOX was
designed and prepared. Firstly, we investigated the accumulation effects of
MTRN/DOX by Prussian blue staining, transmission electron microscopy (TEM), laser
scanning confocal microscopy (LSCM) and conducted 7.0 T MRI. Following this, the
magnetothermal effects of MTRN/DOX were studied using an infrared thermal camera.
DOX uptake, distribution, and retention in tumor cells and the distribution of
MTRN/DOX in vivo were then analyzed via LSCM, flow cytometry and live
fluorescence imaging. Lastly, its anticancer effects were evaluated by MTT, AM/PI
staining, Annexin-VFITC/PI staining and comparison of relative tumor volume.
RESULTS: We found that MTRN/DOX can be efficiently concentrated in the tumor site
through magnetic targeting, increasing the uptake of DOX by tumor cells, and
prolonging the retention time of the drug within the tumors. MTRN/DOX showed good
magnetothermal effects both in vitro and in vivo. Based on the above results,
MTRN/DOX had significant anticancer effects. CONCLUSIONS: MTRN/DOX causes
temporal-spatial synchronism of thermo-chemotherapy and together with
chemotherapeutic drugs, produces a synergistic effect, which enhances the
sensitivity of tumor cells to DOX and reduces their side effects.
PMID- 29344300
TI - General Anesthesia Inhibits the Activity of the "Glymphatic System".
AB - INTRODUCTION: According to the "glymphatic system" hypothesis, brain waste
clearance is mediated by a continuous replacement of the interstitial milieu by a
bulk flow of cerebrospinal fluid (CSF). Previous reports suggested that this
cerebral CSF circulation is only active during general anesthesia or sleep, an
effect mediated by the dilatation of the extracellular space. Given the
controversies regarding the plausibility of this phenomenon and the limitations
of currently available methods to image the glymphatic system, we developed
original whole-brain in vivo imaging methods to investigate the effects of
general anesthesia on the brain CSF circulation. METHODS: We used magnetic
resonance imaging (MRI) and near-infrared fluorescence imaging (NIRF) after
injection of a paramagnetic contrast agent or a fluorescent dye in the cisterna
magna, in order to investigate the impact of general anesthesia (isoflurane,
ketamine or ketamine/xylazine) on the intracranial CSF circulation in mice.
RESULTS:In vivo imaging allowed us to image CSF flow in awake and anesthetized
mice and confirmed the existence of a brain-wide CSF circulation. Contrary to
what was initially thought, we demonstrated that the parenchymal CSF circulation
is mainly active during wakefulness and significantly impaired during general
anesthesia. This effect was especially significant when high doses of anesthetic
agent were used (3% isoflurane). These results were consistent across the
different anesthesia regimens and imaging modalities. Moreover, we failed to
detect a significant change in the brain extracellular water volume using
diffusion weighted imaging in awake and anesthetized mice. CONCLUSION: The
parenchymal diffusion of small molecular weight compounds from the CSF is active
during wakefulness. General anesthesia has a negative impact on the intracranial
CSF circulation, especially when using a high dose of anesthetic agent.
PMID- 29344301
TI - WST11 Vascular Targeted Photodynamic Therapy Effect Monitoring by Multispectral
Optoacoustic Tomography (MSOT) in Mice.
AB - Objective: Monitoring emerging vascular-targeted photodynamic therapy (VTP) and
understanding the time-dynamics of treatment effects remains challenging. We
interrogated whether handheld multispectral optoacoustic tomography (MSOT) could
noninvasively monitor the effect of VTP using WST11, a vascular-acting
photosensitizer, on tumor tissues over time using a renal cell cancer mouse
model. We also investigated whether MSOT illumination can induce VTP, to
implement a single-modality theranostic approach. Materials and Methods: Eight
BalB/c mice were subcutaneously implanted with murine renal adenocarcinoma cells
(RENCA) on the flank. Three weeks later VTP was performed (10 min continuous
illumination at 753 nm following intravenous infusion using WST11 or saline as
control. Handheld MSOT images were collected prior to VTP administration and
subsequently thereafter over the course of the first hour, at 24 and 48 h. Data
collected were unmixed for blood oxygen saturation in tissue (SO2) based on the
spectral signatures of deoxy- and oxygenated hemoglobin. Changes in oxygen
saturation over time, relative to baseline, were examined by paired t-test for
statistical significance (p < 0.05). In-vivo findings were corroborated by
histological analyses of the tumor tissue. Results: MSOT is shown to prominently
resolve changes in oxygen saturation in tumors within the first 20 min post WST11
VTP treatment. Within the first hour post-treatment, SO2 decreased by more than
60% over baseline (p < 0.05), whereas it remained unchanged (p > 0.1) in the sham
treated group. Moreover, unlike in the control group, SO2 in treated tumors
further decreased over the course of 24 to 48 h post-treatment, concomitant with
the propagation of profound central tumor necrosis present in histological
analysis. We further show that pulsed MSOT illumination can activate WST11 as
efficiently as the continuous wave irradiation employed for treatment.
Conclusion: Handheld MSOT non-invasively monitored WST11-VTP effects based on the
SO2 signal and detected blood saturation changes within the first 20 min post
treatment. MSOT may potentially serve as a means for both VTP induction and real
time VTP monitoring in a theranostic approach.
PMID- 29344302
TI - Evans Blue Attachment Enhances Somatostatin Receptor Subtype-2 Imaging and
Radiotherapy.
AB - Purpose: Radionuclide therapy directed against tumors that express somatostatin
receptors (SSTRs) has proven effective for the treatment of advanced, low- to
intermediate-grade neuroendocrine tumors in the clinic. In clinical usage,
somatostatin peptide-based analogs, labeled with therapeutic radionuclides,
provide an overall response rate of about 30%, despite the high cumulative
activity injected per patient. We set out to improve the effectiveness of
somatostatin radiotherapy by preparing a chemical analog that would clear more
slowly through the urinary tract and, concomitantly, have increased blood
circulation half-life and higher targeted accumulation in the tumors.
Experimental Design: We conjugated a common, clinically-used SST peptide
derivative, DOTA-octreotate, to an Evans blue analog (EB), which reversibly binds
to circulating serum albumin. The resulting molecule was used to chelate 86Y and
90Y, a diagnostic and a therapeutic radionuclide, respectively. The imaging
capabilities and the radiotherapeutic efficacy of the resulting radioligand was
evaluated in HCT116/SSTR2, HCT116, and AR42J cell lines that express differing
levels of SST2 receptors. Results: The synthesized radiopharmaceutical retained
affinity and specificity to SSTR2. The new molecule also retained the high
internalization rate of DOTA-octreotate, and therefore, showed significantly
higher accumulation in SSTR2-positive tumors. Labeling of our novel EB-octreotate
derivative with the therapeutic, pure beta emitter, 90Y, resulted in improved
tumor response and survival rates of mice bearing SSTR2 xenografts and had long
term efficacy when compared to DOTA-octreotate itself. Conclusions: The coupling
of a targeted peptide, a therapeutic radionuclide, and the EB-based albumin
binding provides for effective treatment of SSTR2-containing tumors.
PMID- 29344303
TI - Erratum: Improvement of Prostate Cancer Diagnosis by Detecting PSA Glycosylation
Specific Changes: Erratum.
AB - [This corrects the article DOI: 10.7150/thno.15226.].
PMID- 29344304
TI - Atherosclerosis is exacerbated by chitinase-3-like-1 in amyloid precursor protein
transgenic mice.
AB - Although the important role of amyloid precursor protein (APP) in vascular
diseases associated with Alzheimer's disease (AD) has been demonstrated, the
underlying molecular mechanisms and physiological consequences are unclear. We
aimed to evaluate vascular inflammation and atherosclerosis in Swedish mutant of
human APP transgenic (APPsw-Tg) and ApoE-/-/APPsw-Tg mice. We also aimed to
explore the mechanisms underlying any changes observed in these mice compared
with non-Tg controls. Methods: The transgenic and non-Tg mouse strains were
subjected to partial ligation of the left carotid artery to induce
atherosclerotic changes, which were measured using histological approaches,
immunohistochemistry, quantitative polymerase chain reaction, and gene expression
microarrays. Results: Our results showed increased vascular inflammation,
arterial wall thickness, and atherosclerosis in APPsw-Tg and ApoE-/-/APPsw-Tg
mice. We further found that the expression of chitinase-3-like-1 (Chi3l1) is
increased in the APPsw-Tg mouse artery and Chi3l1 mediates endothelial cell (EC)
inflammation and vascular smooth muscle cell (VSMC) activation, which in turn
exacerbates atherosclerosis. In addition, using two publicly available microarray
datasets from the dorsolateral prefrontal cortex of people with AD and unaffected
controls as well as inflamed human umbilical vein endothelial cells, we found
that Chi3l1 and associated inflammatory gene were significantly associated with
AD, evaluated by co-expression network analysis and functional annotation.
Knockdown of Chi3l1 in the arterial endothelium in vivo suppressed the
development of atherosclerosis. We also show that microRNA 342-3p (miR-342-3p)
inhibits EC inflammation and VSMC activation through directly targeting Chi3l1,
and that APPsw increased Chi3l1 expression by reducing miR-342-3p expression in
the arterial endothelium, promoting atherosclerosis. Conclusion: Our findings
suggest that targeting Chi3l1 might provide new diagnostic and therapeutic
strategies for vascular diseases in patients with AD.
PMID- 29344305
TI - A Tumor-Activatable Theranostic Nanomedicine Platform for NIR Fluorescence-Guided
Surgery and Combinatorial Phototherapy.
AB - Fluorescence image-guided surgery combined with intraoperative therapeutic
modalities has great potential for intraoperative detection of oncologic targets
and eradication of unresectable cancer residues. Therefore, we have developed an
activatable theranostic nanoplatform that can be used concurrently for two
purposes: (1) tumor delineation with real-time near infrared (NIR) fluorescence
signal during surgery, and (2) intraoperative targeted treatment to further
eliminate unresected disease sites by non-toxic phototherapy. Methods: The
developed nanoplatform is based on a single agent, silicon naphthalocyanine
(SiNc), encapsulated in biodegradable PEG-PCL (poly (ethylene glycol)-b-poly(E
caprolactone)) nanoparticles. It is engineered to be non-fluorescent initially
via dense SiNc packing within the nanoparticle's hydrophobic core, with NIR
fluorescence activation after accumulation at the tumor site. The activatable
nanoplatform was evaluated in vitro and in two different murine cancer models,
including an ovarian intraperitoneal metastasis-mimicking model. Furthermore,
fluorescence image-guided surgery mediated by this nanoplatform was performed on
the employed animal models using a Fluobeam(r) 800 imaging system. Finally, the
phototherapeutic efficacy of the developed nanoplatform was demonstrated in vivo.
Results: Our in vitro data suggest that the intracellular environment of cancer
cells is capable of compromising the integrity of self-assembled nanoparticles
and thus causes disruption of the tight dye packing inside the hydrophobic cores
and activation of the NIR fluorescence. Animal studies demonstrated accumulation
of activatable nanoparticles at the tumor site following systemic administration,
as well as release and fluorescence recovery of SiNc from the polymeric carrier.
It was also validated that the developed nanoparticles are compatible with the
intraoperative imaging system Fluobeam(r) 800, and nanoparticle-mediated image
guided surgery provides successful resection of cancer tumors. Finally, in vivo
studies revealed that combinatorial phototherapy mediated by the nanoparticles
could efficiently eradicate chemoresistant ovarian cancer tumors. Conclusion: The
revealed properties of the activatable nanoplatform make it highly promising for
further application in clinical image-guided surgery and combined phototherapy,
facilitating a potential translation to clinical studies.
PMID- 29344306
TI - 131I-Labeled Copper Sulfide-Loaded Microspheres to Treat Hepatic Tumors via
Hepatic Artery Embolization.
AB - Purpose: Transcatheter hepatic artery embolization therapy is a minimally
invasive alternative for treating inoperable liver cancer but recurrence is
frequent. Multifunctional agents, however, offer an opportunity for tumor
eradication. In this study, we were aim to synthesized poly (lactic-co-glycolic
acid) (PLGA) microspheres encapsulating hollow CuS nanoparticles (HCuSNPs) and
paclitaxel (PTX) that were then labeled with radioiodine-131 (131I) to produce
131I-HCuSNPs-MS-PTX. This compound combines the multi-theranostic properties of
chemotherapy, radiotherapy and photothermal therapy. In addition, it can also be
imaged with single photon emission computed tomography (SPECT) imaging and
photoacoustic imaging. Methods: We investigated the value of therapeutic and
imaging of 131I-HCuSNPs-MS-PTX in rats bearing Walker-256 tumor transplanted in
the liver. After the intra-arterial (IA) injection of 131I-HCuSNPs-MS-PTX, 18F
Fluorodeoxyglucose (18F-FDG) micro-positron emission tomography/computed
tomography (micro-PET/CT) imaging was used to monitor the therapeutic effect.
PET/CT findings were verified by immunohistochemical analysis. SPECT/CT and
photoacoustic imaging were performed to demonstrate the distribution of 131I
HCuSNPs-MS-PTX in vivo. Results: We found that embolization therapy in
combination with chemotherapy, radiotherapy and photothermal therapy offered by
131I-HCuSNPs-MS-PTX completely ablated the transplanted hepatic tumors at a
relatively low dose. In comparison, embolization monotherapy or combination with
one or two other therapies had less effective anti-tumor efficacy. The
combination of SPECT/CT and photoacoustic imaging effectively confirmed
microsphere delivery to the targeted tumors in vivo and guided the near-infrared
laser irradiation. Conclusion: Our study suggests that there is a clinical
theranostic potential for imaging-guided arterial embolization with 131I-HCuSNPs
MS-PTX for the treatment of liver tumors.
PMID- 29344307
TI - Dual turn-on fluorescence signal-based controlled release system for real-time
monitoring of drug release dynamics in living cells and tumor tissues.
AB - Controlled release systems with capabilities for direct and real-time monitoring
of the release and dynamics of drugs in living systems are of great value for
cancer chemotherapy. Herein, we describe a novel dual turn-on fluorescence signal
based controlled release system (CDox), in which the chemotherapy drug
doxorubicin (Dox) and the fluorescent dye (CH) are conjugated by a hydrazone
moiety, a pH-responsive cleavable linker. CDox itself shows nearly no
fluorescence as the fluorescence of CH and Dox is essentially quenched by the C=N
isomerization and N-N free rotation. However, when activated under acidic
conditions, CDox could be hydrolyzed to afford Dox and CH, resulting in dual turn
on signals with emission peaks at 595 nm and 488 nm, respectively. Notably, CDox
exhibits a desirable controlled release feature as the hydrolysis rate is limited
by the steric hindrance effect from both the Dox and CH moieties. Cytotoxicity
assays indicate that CDox shows much lower cytotoxicity relative to Dox, and
displays higher cell inhibition rate to cancer than normal cells. With the aid of
the dual turn-on fluorescence at different wavelengths, the drug release dynamics
of CDox in living HepG2 and 4T-1 cells was monitored in double channels in a real
time fashion. Importantly, two-photon fluorescence imaging of CDox in living
tumor tissues was also successfully performed by high-definition 3D imaging. We
expect that the unique controlled release system illustrated herein could provide
a powerful means to investigate modes of action of drugs, which is critical for
development of much more robust and effective chemotherapy drugs.
PMID- 29344308
TI - "Albumin Hitchhiking" with an Evans Blue Analog for Cancer Theranostics.
AB - Although 177Lu-DOTA-TATE was recently approved in Europe for the treatment of
certain neuroendocrine tumors, continued development and optimization has been
ongoing to further improve the therapeutic efficacy of somatostatin receptor 2
targeted peptide receptor radionuclide therapy, as well as reducing the renal
toxicity. In this work, the use of an Evans blue analog for "albumin hitchhiking"
resulted in significant improvement in both the imaging performance and
therapeutic efficacy of radiolabeled octreotate, as well as reducing the toxicity
since much less radioactivity was used for therapy. Upon clinical translation,
such "albumin hitchhiking" could make significant impact in the near future for
cancer patient management.
PMID- 29344310
TI - Drug Repurposing Screening Identifies Tioconazole as an ATG4 Inhibitor that
Suppresses Autophagy and Sensitizes Cancer Cells to Chemotherapy.
AB - Background: Tumor cells require proficient autophagy to meet high metabolic
demands and resist chemotherapy, which suggests that reducing autophagic flux
might be an attractive route for cancer therapy. However, this theory in clinical
cancer research remains controversial due to the limited number of drugs that
specifically inhibit autophagy-related (ATG) proteins. Methods: We screened FDA
approved drugs using a novel platform that integrates computational docking and
simulations as well as biochemical and cellular reporter assays to identify
potential drugs that inhibit autophagy-required cysteine proteases of the ATG4
family. The effects of ATG4 inhibitors on autophagy and tumor suppression were
examined using cell culture and a tumor xenograft mouse model. Results:
Tioconazole was found to inhibit activities of ATG4A and ATG4B with an IC50 of
1.3 uM and 1.8 uM, respectively. Further studies based on docking and molecular
dynamics (MD) simulations supported that tioconazole can stably occupy the active
site of ATG4 in its open form and transiently interact with the allosteric
regulation site in LC3, which explained the experimentally observed obstruction
of substrate binding and reduced autophagic flux in cells in the presence of
tioconazole. Moreover, tioconazole diminished tumor cell viability and sensitized
cancer cells to autophagy-inducing conditions, including starvation and treatment
with chemotherapeutic agents. Conclusion: Tioconazole inhibited ATG4 and
autophagy to enhance chemotherapeutic drug-induced cytotoxicity in cancer cell
culture and tumor xenografts. These results suggest that the antifungal drug
tioconazole might be repositioned as an anticancer drug or chemosensitizer.
PMID- 29344311
TI - Gilz-Activin A as a Novel Signaling Axis Orchestrating Mesenchymal Stem Cell and
Th17 Cell Interplay.
AB - Mesenchymal stem cells (MSC) are highly immunosuppressive cells able to reduce
chronic inflammation through the active release of mediators. Recently, we showed
that glucocorticoid-induced leucine zipper (Gilz) expression by MSC is involved
in their therapeutic effect by promoting the generation of regulatory T cells.
However, the mechanisms underlying this pivotal role of Gilz remain elusive.
Methods and Results In this study, we have uncovered evidence that Gilz modulates
the phenotype and function of Th1 and Th17 cells likely by upregulating the level
of Activin A and NO2 secreted by MSC. Adoptive transfer experiments sustained
this Gilz-dependent suppressive effect of MSC on Th1 and Th17 cell functions. In
immunoregulatory MSC, obtained by priming with IFN-gamma and TNF-alpha, Gilz was
translocated to the nucleus and bound to the promoters of inos and Activin betaA
to induce their expression. The increased expression of Activin A directly
impacted on Th17 cells fate by repressing their differentiation program through
the activation of Smad3/2 and enhancing IL-10 production. Conclusion Our results
reveal how Gilz controls inos and Activin betaA gene expression to ultimately
assign immunoregulatory status to MSC able to repress the pathogenic Th17 cell
differentiation program and uncover Activin A as a novel mediator of MSC in this
process.
PMID- 29344309
TI - Adult Stem Cells in Vascular Remodeling.
AB - Understanding the contribution of vascular cells to blood vessel remodeling is
critical for the development of new therapeutic approaches to cure cardiovascular
diseases (CVDs) and regenerate blood vessels. Recent findings suggest that
neointimal formation and atherosclerotic lesions involve not only inflammatory
cells, endothelial cells, and smooth muscle cells, but also several types of stem
cells or progenitors in arterial walls and the circulation. Some of these stem
cells also participate in the remodeling of vascular grafts, microvessel
regeneration, and formation of fibrotic tissue around biomaterial implants. Here
we review the recent findings on how adult stem cells participate in CVD
development and regeneration as well as the current state of clinical trials in
the field, which may lead to new approaches for cardiovascular therapies and
tissue engineering.
PMID- 29344312
TI - An Endogenous Vaccine Based on Fluorophores and Multivalent Immunoadjuvants
Regulates Tumor Micro-Environment for Synergistic Photothermal and Immunotherapy.
AB - Recently, near-infrared (NIR) light-based photothermal therapy (PTT) has been
widely applied in cancer treatment. However, in most cases, the tissue
penetration depth of NIR light is not sufficient and thus photothermal therapy is
unable to completely eradicate deep, seated tumors inevitably leading to
recurrence of the tumor. Due to this significant limitation of NIR, improved
therapeutic strategies are urgently needed. Methods: We developed an endogenous
vaccine based on a novel nanoparticle platform for combinatorial photothermal
ablation and immunotherapy. The design was based on fluorophore-loaded liposomes
(IR-7-lipo) coated with a multivalent immunoadjuvant (HA-CpG). In vitro PTT
potency was assessed in cells by LIVE/DEAD and Annexin V-FITC/PI assays. The
effect on bone marrow-derived dendritic cells (BMDC) maturation and antigen
presentation was evaluated by flow cytometry (FCM) with specific antibodies.
After treatment, the immune cell populations in tumor micro-environment and the
cytokines in the serum were detected by FCM and Elisa assay, respectively.
Finally, the therapeutic outcome was investigated in an animal model. Results:
Upon irradiation with 808 nm laser, IR-7-lipo induced tumor cell necrosis and
released tumor-associated antigens, while the multivalent immunoadjuvant improved
the expression of co-stimulatory molecules on BMDC and promoted antigen
presentation. The combination therapy of PTT and immunotherapy regulated the
tumor micro-environment, decreased immunosuppression, and potentiated host
antitumor immunity. Most significantly, due to an enhanced antitumor immune
response, combined photothermal immunotherapy was effective in eradicating tumors
in mice and inhibiting tumor metastasis. Conclusion: This endogenous vaccination
strategy based on synergistic photothermal and immunotherapy may provide a
potentially effective approach for treatment of cancers, especially those
difficult to be surgically removed.
PMID- 29344313
TI - DNA methylation as a predictor of fetal alcohol spectrum disorder.
AB - Background: Fetal alcohol spectrum disorder (FASD) is a developmental disorder
that manifests through a range of cognitive, adaptive, physiological, and
neurobiological deficits resulting from prenatal alcohol exposure. Although the
North American prevalence is currently estimated at 2-5%, FASD has proven
difficult to identify in the absence of the overt physical features
characteristic of fetal alcohol syndrome. As interventions may have the greatest
impact at an early age, accurate biomarkers are needed to identify children at
risk for FASD. Building on our previous work identifying distinct DNA methylation
patterns in children and adolescents with FASD, we have attempted to validate
these associations in a different clinical cohort and to use our DNA methylation
signature to develop a possible epigenetic predictor of FASD. Methods: Genome
wide DNA methylation patterns were analyzed using the Illumina
HumanMethylation450 array in the buccal epithelial cells of a cohort of 48
individuals aged 3.5-18 (24 FASD cases, 24 controls). The DNA methylation
predictor of FASD was built using a stochastic gradient boosting model on our
previously published dataset FASD cases and controls (GSE80261). The predictor
was tested on the current dataset and an independent dataset of 48 autism
spectrum disorder cases and 48 controls (GSE50759). Results: We validated
findings from our previous study that identified a DNA methylation signature of
FASD, replicating the altered DNA methylation levels of 161/648 CpGs in this
independent cohort, which may represent a robust signature of FASD in the
epigenome. We also generated a predictive model of FASD using machine learning in
a subset of our previously published cohort of 179 samples (83 FASD cases, 96
controls), which was tested in this novel cohort of 48 samples and resulted in a
moderately accurate predictor of FASD status. Upon testing the algorithm in an
independent cohort of individuals with autism spectrum disorder, we did not
detect any bias towards autism, sex, age, or ethnicity. Conclusion: These
findings further support the association of FASD with distinct DNA methylation
patterns, while providing a possible entry point towards the development of
epigenetic biomarkers of FASD.
PMID- 29344315
TI - A Topical Anti-inflammatory Healing Regimen Utilizing Conjugated Linolenic Acid
for Use Post-ablative Laser Resurfacing of the Face: A Randomized, Controlled
Trial.
AB - Background: Fractionated, ablative lasers are usually associated with post
treatment erythema, edema, and crusting, which can last from 5 to 14 days.
Conjugated linolenic acid, an omega-5 fatty acid, has significant antioxidant and
anti-inflammatory properties, and has been shown to stimulate keratinocyte
proliferation and epidermal regeneration. By modulating the early inflammatory
milieu and directly affecting skin structure and function, conjugated linolenic
acid might therefore shorten downtime following fractionated ablative laser
resurfacing of the face. Objective: To evaluate the efficacy and subject
satisfaction of a topical regimen containing conjugated linolenic acid derived
from pomegranate seed extract in accelerating wound healing and improving skin
quality following fractionated ablative laser resurfacing of the face. Materials
and Methods: Thirty-four subjects were enrolled and received fractionated CO2
laser resurfacing. Subjects were randomized to use the test healing regimen
(n=24) or 1% dimethicone ointment (n=10) post-procedure. The primary endpoint was
the degree of erythema, edema, crusting, and exudation evaluated by a blinded
clinician at post-treatment Days 1,3,7,10, 14, and 30. Secondary endpoints
included a blinded evaluator assessment of the degree of wrinkling and elastosis
using the Fitzpatrick-Goldman Wrinkle and Elastosis Scale; subject-assessed
degree of pain, itching, tightness, oozing, and crusting; and subject overall
satisfaction. Results: Subjects who applied the topical conjugated linolenic acid
healing regimen experienced significantly reduced edema on post-procedure Day 3
(p=0.04), and itching on Days 1 and 3 (p=0.03 and p=0.04). Both regimens produced
significant improvements in wrinkling and elastosis at Days 14 and 30 post
treatment, with conjugated linolenic acid outperforming placebo in improvements
in wrinkling at Day 14. Both regimens were well tolerated with no statistical
differences in adverse events or subject satisfaction. Conclusion: The topical
conjugated linolenic acid formulation outperformed placebo by decreasing acute
pruritus and edema, and enabling a faster positive outcome in wrinkle
improvement. Additionally, topical conjugated linolenic acid does not raise any
safety or tolerability issues as compared to current standard of care.
PMID- 29344314
TI - Aberrant expression and DNA methylation of lipid metabolism genes in PCOS: a new
insight into its pathogenesis.
AB - Background: Polycystic ovary syndrome (PCOS), whose etiology remains uncertain,
is a highly heterogenous and genetically complex endocrine disorder. The aim of
this study was to identify differentially expressed genes (DEGs) in granulosa
cells (GCs) from PCOS patients and make epigenetic insights into the pathogenesis
of PCOS. Results: Included in this study were 110 women with PCOS and 119 women
with normal ovulatory cycles undergoing in vitro fertilization acting as the
control group. RNA-seq identified 92 DEGs unique to PCOS GCs in comparison with
the control group. Bioinformatic analysis indicated that synthesis of lipids and
steroids was activated in PCOS GCs. 5-Methylcytosine analysis demonstrated that
there was an approximate 25% reduction in global DNA methylation of GCs in PCOS
women (4.44 +/- 0.65%) compared with the controls (6.07 +/- 0.72%; P < 0.05).
Using MassArray EpiTYPER quantitative DNA methylation analysis, we also found
hypomethylation of several gene promoters related to lipid and steroid synthesis,
which might result in the aberrant expression of these genes. Conclusions: Our
results suggest that hypomethylated genes related to the synthesis of lipid and
steroid may dysregulate expression of these genes and promote synthesis of
steroid hormones including androgen, which could partially explain mechanisms of
hyperandrogenism in PCOS.
PMID- 29344317
TI - Survey of Dermatologists and Venereologists Shows Varying Approach to Penile
Biopsies.
AB - OBJECTIVE: To determine frequency of use and safety of epinephrine containing
local anesthesia among dermatologists in the United Kingdom and venereologists
undertaking penile biopsy. DESIGN: A survey was distributed nationally to members
of the British Association of Dermatologists and the British Association for
Sexual Health and Human Immunodeficiency Virus in December 2016. RESULTS: Sixty
six responses were received: 36.4 percent of respondents used epinephrine
routinely, 16.7 percent sometimes used it, and 47 percent did not use it at all.
Epinephrine use was more commonly by dermatologists in either some or all cases
(56.8%) compared with venereologists (40%). Only two complications were reported
to epinephrine use. Both were temporary without report of necrosis. CONCLUSION:
Use of epinephrine-containing local anesthesia is common among physicians in the
United Kingdom undertaking penile biopsies. Despite this, no episodes of necrosis
were observed. While further investigation is still required, it is likely that
use of epinephrine-containing local anesthesia is safe for local penile
injection.
PMID- 29344316
TI - Clinical, Biochemical, and Hormonal Associations in Female Patients with Acne: A
Study and Literature Review.
AB - Female acne is often associated with clinical signs of hyperandrogenism or
metabolic syndrome. Various hormonal and biochemical factors as well as Vitamin D
deficiency play a role in the etiopathogenesis of acne, and it is important to be
able to detect the altered marker(s) indicative of certain abnormalities in order
to diagnose and treat the cause. However, interpretation of these markers can be
difficult, as there is ambiguity as to what is considered "normal" or "abnormal."
The aim of this study was to explore the associations that acne might have with
certain clinical, hormonal, and biological factors among female patients with
acne. Additionally, the available literature was reviewed in order to determine
the prevalence of these associations, discussion of which is provided. The
author's investigations reveal a very high prevalence of abnormal metabolic and
hormonal statuses among women with acne, indicating the need for dermatologists
to maintain a high index of suspician for other disorders, especially metabolic
disorders (and in particular, polycystic ovary syndrome), when treating female
patients with acne.
PMID- 29344318
TI - Noninvasive Long-term Monitoring of Actinic Keratosis and Field Cancerization
Following Treatment with Ingenol Mebutate Gel 0.015.
AB - OBJECTIVE: To determine whether actinic keratosis and photodamaged perilesional
areas (field cancerization) treated successfully with topical ingenol mebutate
gel 0.015% remained clear one year later, and to treat actinic keratosis and
perilesional skin not treated one year earlier. DESIGN: Single-center, single
arm, open-label extension of an original clinical study completed one year
earlier. SETTING: An outpatient clinic. PARTICIPANTS: Fifteen of the original 28
study patients enrolled in and who completed the extension phase. MEASUREMENTS:
All treated and untreated lesions in the original study were evaluated
clinically, dermoscopically, and with optical coherence tomography at Day 0 of
the extension study. Previously untreated lesions were then treated with ingenol
mebutate gel 0.015% for three days and reevaluated at Day 60. RESULTS: There was
no significant increase in actinic keratoses over one year. The majority of
actinic keratoses not treated in the original study were still present at the
beginning of the extension study. Following treatment, 69 percent of these
lesions cleared by Day 60 of the extension study, which was not significantly
different from the 79 percent clearance observed in the original study.
CONCLUSION: Ingenol mebutate 0.015% maintained clearance of lesions treated one
year earlier. Optical coherence therapy demonstrated its reliability as a
noninvasive mode of diagnosis for actinic keratosis as well as actinic damage in
the surrounding areas of field cancerization. Optical coherence therapy also
showed that previously untreated lesions exhibited similar clearance rates once
treated with the medication.
PMID- 29344319
TI - Sandalwood Album Oil as a Botanical Therapeutic in Dermatology.
AB - Many skin conditions and diseases are characterized by inflammation, infection,
and hyperplasia. Safe and effective topical treatment options that can be used
long-term are needed. Traditional botanical medicines, which are often complex
mixtures that exert their biological activities via multiple mechanisms of
action, are being studied as potential new active ingredients in dermatology.
Sandalwood album oil (SAO), also known as East Indian sandalwood oil (EISO), is
an essential oil distilled from the Santalum album tree and has demonstrated
biological activity as an anti-inflammatory, anti-microbial, and anti
proliferative agent. Sandalwood album oil has also shown promise in clinical
trials for treatment of acne, psoriasis, eczema, common warts, and molluscum
contagiosum. The favorable safety profile, ease of topical use, and recent
availability of pharmaceutical-grade sandalwood album oil support its broader use
as the basis of novel therapies in dermatology.
PMID- 29344320
TI - Pyoderma Gangrenosum-associated Granulomatosis with Polyangitis: A Case Report
and Literature Review.
AB - Granulomatosis with polyangitis, formerly known as Wegener's granulomatosis, is a
multi-system vasculitis that has a variable clinical presentation. Although
uncommon, cutaneous symptoms can be the initial presenting symptom of
granulomatosis with polyangitis. We present an unusual case of pyoderma
gangrenosum followed by a diagnosis of granulomatosis with polyangitis. We also
provide a review of current literature on therapeutic options.
PMID- 29344321
TI - Fixed Drug Eruption to Supplement Containing Ginkgo Biloba and Vinpocetine: A
Case Report and Review of Related Cutaneous Side Effects.
AB - BACKGROUND: Fixed drug eruption is a cutaneous reaction to a systemic agent that
typically presents as an annular or oval erythematous patch or blister and
subsequently resolves with postinflammatory hyperpigmentation at the site. Ginkgo
biloba leaf extract and vinpocetine are nutritional supplements used to enhance
memory in patients with dementia and age-related memory impairment conditions
such as Alzheimer's disease. PURPOSE: To describe a fixed drug eruption in a man
who repeatedly developed pruritus and macular erythema on his distal penile shaft
after ingesting a natural product containing Ginkgo biloba and vinpocetine.
METHODS: The medical literature was retrospectively reviewed using PubMed,
searching specifically for the terms cutaneous/skin adverse/side effects, fixed
drug eruption, Ginkgo biloba, and vinpocetine. Patient reports and previous
reviews of the subject were critically assessed, and the salient features of
cutaneous adverse effects in patients receiving either Ginkgo biloba or
vinpocetine are presented. RESULTS: Cutaneous adverse effects from Ginkgo biloba
and vinpocetine are infrequent. Ginkgo biloba fruit can result in contact
dermatitis (following topical exposure) and mucosal symptoms of the mouth and
anus (following oral exposure); in addition, an erythematous maculopapular
generalized eruption or possibly Steven-Johnson syndrome can occur after oral
ingestion of the Ginkgo biloba leaf extract. Facial erythema has been associated
with vinpocetine ingestion. Pruritus and an annular erythema localized to the
distal penile shaft developed after initial and repeat ingestion of a Ginkgo
biloba/vinpocetine product. CONCLUSION:Ginkgo biloba and vinpocetine should be
added to the agents that can potentially cause a fixed drug eruption.
PMID- 29344323
TI - The Impact of Quantitative Data Provided by a Multi-spectral Digital Skin Lesion
Analysis Device on Dermatologists'Decisions to Biopsy Pigmented Lesions.
AB - BACKGROUND: Early diagnosis of melanoma is critical to survival. New
technologies, such as a multi-spectral digital skin lesion analysis (MSDSLA)
device [MelaFind, STRATA Skin Sciences, Horsham, Pennsylvania] may be useful to
enhance clinician evaluation of concerning pigmented skin lesions. Previous
studies evaluated the effect of only the binary output. OBJECTIVE: The objective
of this study was to determine how decisions dermatologists make regarding
pigmented lesion biopsies are impacted by providing both the underlying
classifier score (CS) and associated probability risk provided by multi-spectral
digital skin lesion analysis. This outcome was also compared against the
improvement reported with the provision of only the binary output. METHODS:
Dermatologists attending an educational conference evaluated 50 pigmented lesions
(25 melanomas and 25 benign lesions). Participants were asked if they would
biopsy the lesion based on clinical images, and were asked this question again
after being shown multi-spectral digital skin lesion analysis data that included
the probability graphs and classifier score. RESULTS: Data were analyzed from a
total of 160 United States board-certified dermatologists. Biopsy sensitivity for
melanoma improved from 76 percent following clinical evaluation to 92 percent
after quantitative multi-spectral digital skin lesion analysis information was
provided (p<0.0001). Specificity improved from 52 percent to 79 percent
(p<0.0001). The positive predictive value increased from 61 percent to 81 percent
(p<0.01) when the quantitative data were provided. Negative predictive value also
increased (68% vs. 91%, p<0.01), and overall biopsy accuracy was greater with
multi-spectral digital skin lesion analysis (64% vs. 86%, p<0.001). Interrater
reliability improved (intraclass correlation 0.466 before, 0.559 after).
CONCLUSION: Incorporating the classifier score and probability data into
physician evaluation of pigmented lesions led to both increased sensitivity and
specificity, thereby resulting in more accurate biopsy decisions.
PMID- 29344322
TI - Acne Scarring-Pathogenesis, Evaluation, and Treatment Options.
AB - Acne vulgaris is a ubiquitous problem affecting 80 percent of people ages 11 to
30 years, with many patients experiencing some degree of scarring. This review
focuses on atrophic scars, the most common type of acne scar. We briefly address
the cellular sequelae that lead to scar formation and the initial evaluation of
patients with acne scars. We then discuss an algorithmic approach to the
treatment of acne scarring based on the classification of scars into erythematous
and atrophic types. Lastly, we discuss the future treatment of acne scars and
ongoing clinical trials.
PMID- 29344324
TI - Treatment of Lateral Periorbital Lines with Different Dilutions of
IncobotulinumtoxinA.
AB - BACKGROUND: IncobotulinumtoxinA is a botulinum neurotoxin type A that is free
from complexing proteins and is used in various therapeutic indications and
aesthetic medicine. It is approved for the treatment of glabellar frown lines in
the United States. In Europe, it is also approved for the treatment of lateral
periorbital lines (crow's feet) and for the combined treatment of upper facial
lines, including glabellar frown lines, crow's feet, and horizontal forehead
lines. METHODS: In the present study, incobotulinumtoxinA was injected at two
different dilutions to treat female subjects aged 40 to 50 years who had moderate
to-severe lateral periorbital lines at maximum contraction according to a score
of 2 or 3 points on the 5-point Merz Aesthetics Scales (MAS). For Group 1 (n=20),
50U of incobotulinumtoxinA were reconstituted with 1.60mL of 0.9% NaCI, and for
Group 2 (n=20), a reconstitution volume of 0.55mL was used. RESULTS: Merz
Aesthetics Scales scores were markedly improved by at least one point in both
groups at one month and three months. The mean Merz Aesthetics Scales scores at
one month were 0.4 and 0.6 points for Group 1 and Group 2, respectively,
corresponding to a mean improvement of 2.0 and 1.8 points compared with baseline,
respectively. CONCLUSION: No significant differences in efficacy and tolerability
of incobotulinumtoxinA were seen between the two dilutions at any time point.
PMID- 29344325
TI - Polycystic Ovarian Syndrome-associated Confluent and Reticulated Papillomatosis:
Report of a Patient Successfully Treated with Azithromycin.
AB - Polycystic ovarian syndrome is a common endocrine disorder with a variety of
dermatologic manifestations among young women. Confluent and reticulated
papillomatosis is a rare dermatosis of unknown etiology that is seldom reported
in patients with polycystic ovarian syndrome. We describe the case of a young
woman with obesity, confluent and reticulated papillomatosis, and concurrent
acanthosis nigricans. Her history, physical examination, and laboratory
evaluation led to the diagnosis of polycystic ovarian syndrome. The proposed
etiologies and the various of treatment options for confluent and reticulated
papillomatosis are discussed. In our case, the patient had a dramatic response to
treatment with azithromycin. The etiology of confluent and reticulated
papillomatosis remains to be established. Additionally, the mechanism behind the
success of treatment with antibiotics is unclear; however, in this patient,
azithromycin was a safe and effective option for the treatment of confluent and
reticulated papillomatosis.
PMID- 29344326
TI - Non-response to Interleukin-1 Antagonist Canakinumab in Two Patients with
Refractory Pyoderma Gangrenosum and Hidradenitis Suppurativa.
AB - Pyoderma gangrenosum and hidradenitis suppurativa are skin conditions
characterized by an intense neutrophil-mediated inflammatory response that is
often difficult to effectively treat. Successful use of interleukin (IL)-1beta
inhibition using canakinumab and anakinra has been reported in patients with
concomitant pyoderma gangrenosum and hidradenitis suppurativa. We report two
cases where targeted therapy with canakinumab failed to lead to improvement for
patients with pyoderma gangrenosum and hidradenitis suppurativa. The reason
behind the non-response to IL-1beta blockade seen in these patients is unclear.
Our report suggests that further controlled studies are warranted to help
clinicians predict treatment responses to anti-IL-1 therapies in these
challenging patients.
PMID- 29344327
TI - Secukinumab: a review of the anti-IL-17A biologic for the treatment of psoriasis.
AB - Psoriasis is a systemic inflammatory disease associated with numerous
comorbidities and a profound impact on patients' quality of life. While its
complex immune pathogenesis is still not fully delineated, current evidence
supports a fundamental role of the T-helper-17 (TH-17) pathway and its related
interleukin-17 (IL-17) cytokine. Thus, new antipsoriatic therapies have been
developed to block this key cytokine and its downstream effects. Secukinumab is a
fully humanized, monoclonal anti-IL-17A antibody, and the first in its class to
be approved by the US Food and Drug Administration for the treatment of moderate
to severe plaque psoriasis. It has also been approved for the treatment of active
psoriatic arthritis and ankylosing spondylitis. Its clinical efficacy in plaque
psoriasis has been well demonstrated in numerous phase II and III clinical
trials. In addition, it has shown superiority in clinical trials to current
biologic agents including etanercept and ustekinumab, with a safe adverse event
profile. In correlation with excellent skin improvements, secukinumab is also
associated with significant improvements in health-related quality of life
measures. Thus, secukinumab offers the potential for equal, or improved,
therapeutic effects compared with other biologics, and is a valuable addition to
our current antipsoriatic armamentarium.
PMID- 29344328
TI - Management of functional dyspepsia: state of the art and emerging therapies.
AB - Patients with functional dyspepsia, defined in the 2016 Rome IV criteria as
bothersome clinical dyspepsia symptoms, experience markedly reduced quality of
life. Several etiologies have been associated with the disorder. In the Rome IV
criteria, the brain-gut axis was acknowledged as an important factor in the
etiology of functional gastrointestinal (GI) disorders. The distinct subgroups of
functional dyspepsia, epigastric pain syndrome (EPS) and postprandial distress
syndrome (PDS), are treated differently: acid secretion inhibitors are
recommended with patients with EPS, whereas prokinetic drugs as mosapride and
acotiamide are recommended for patients with PDS. A previous study has reported
that proton pump inhibitors (PPIs) and H2-blockers were equally effective in
functional dyspepsia. A new drug, acotiamide, a muscarinic antagonist and
cholinesterase inhibitor, has been shown to improve gastric motility in rodents
and dogs, and to reduce PDS symptoms in patients in double-blind multicenter
studies. The pharmacological mechanisms of acotiamide remain unknown; whether
acotiamide alters gastric emptying and gastric accommodation in patients with
functional dyspepsia remains an open question. Other emerging treatment options
include Rikkunshito, a herbal medicine that improves gastric emptying through 5
hydroxytryptamine (5-HT)2B-mediated pharmacological action, and tricyclic
antidepressants (TCAs). Different drugs are needed to accommodate the clinical
symptoms and etiology in individual patients.
PMID- 29344329
TI - Major adverse cardiovascular event reduction with GLP-1 and SGLT2 agents:
evidence and clinical potential.
AB - Treatment of patients with type 2 diabetes is directed against treating symptoms
of hyperglycemia, minimizing the risk of hypoglycemia, and the risk of
microvascular and macrovascular complications. The majority of patients with type
2 diabetes die from cardiovascular or cerebrovascular disease. Future therapies
should therefore focus on reducing cardiovascular morbidity in this high-risk
population. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium
glucose co-transporter 2 inhibitors (SGLT2-i) are two drug classes with proven
antihyperglycemic effect in type 2 diabetes. However, these drugs seem to have
other effects such as weight reduction, low risk of hypoglycemia, and blood
pressure reduction. Emerging evidence suggests pleiotropic effects, which
potentially could be important in reducing cardiovascular risk. Prompted by
regulatory authorities demanding cardiovascular outcome trials (CVOTs) assessing
the cardiovascular safety of new antihyperglycemic drug candidates, many CVOTs
are ongoing and a few of these are finalized. Somewhat surprising recent CVOTs in
both drug classes have shown promising data on cardiovascular morbidity and
mortality in patients with a very high risk of cardiovascular events. It is
uncertain whether this is a class effect of the two drug classes, and it is yet
unproven whether long-term cardiovascular benefits of these drugs can be
extrapolated to populations at lower risk of cardiovascular disease. The aim of
the present review is to give an overview of our current knowledge of the GLP-1RA
and SGLT2-i classes, with specific focus on mechanisms of action, effects on
cardiovascular risk factors and cardiovascular morbidity and mortality from the
CVOTs presently available. The clinical potential of these data is discussed.
PMID- 29344330
TI - Developments in rare bone diseases and mineral disorders.
AB - In the last decade, there have been a number of significant advances made in the
field of rare bone diseases. In this review, we discuss the expansion of the
classification system for osteogenesis imperfecta (OI) and the resultant increase
in therapeutic options available for management of OI. Bisphosphonates remain the
most widely used intervention for OI, although the effect on fracture rate
reduction is equivocal. We review the other therapies showing promising results,
including denosumab, teriparatide, sclerostin, transforming growth factor beta
inhibition and gene targeted approaches. X-linked hypophosphataemia (XLH) is the
most common heritable form of osteomalacia and rickets caused by a mutation in
the phosphate regulating endopeptidase gene resulting in elevated serum
fibroblast growth factor 23 (FGF23) and decreased renal phosphate reabsorption.
The traditional treatment is phosphate replacement. We discuss the development of
a human anti-FGF23 antibody (KRN23) as a promising development in the treatment
of XLH. The current management of primary hypoparathyroidism is replacement with
calcium and active vitamin D. This can be associated with under or over
replacement and its inherent complications. We review the use of recombinant
parathyroid hormone (1-84), which can significantly reduce the requirements for
calcium and vitamin D resulting in greater safety and quality of life for
individuals with hypoparathyroidism. The use of receptor activator of nuclear
factor kappaB ligand infusions in the treatment of a particular form of
osteopetrosis and enzyme replacement therapy for hypophosphatasia are also
discussed.
PMID- 29344331
TI - The Peripheral Flicker Illusion.
AB - A new illusion is reported. A visual object suddenly appearing on a red
background sometimes causes an impression of flicker or double flash. In
Experiment 1, a red, green, or blue object was presented on a red, green, blue,
or gray background. Participants evaluated the illusion strength in reference to
the physical flicker of a gray object presented in central vision. The results
show that the green or blue object presented on the red background caused the
illusion. In Experiment 2, the effect of retinal eccentricity on the illusion was
tested. The results showed that the illusion was weak in central vision but
became stronger as the retinal eccentricity of the objects' presentation
increased. In Experiment 3, optimal luminance conditions for the illusion were
explored with the green and blue objects. The illusion was strong when object
luminance was lower than background luminance and the optimal luminance for the
blue object was lower than that for the green object. We propose a tentative
theory for the illusion and discuss its cause.
PMID- 29344332
TI - Kitaoka's Tomato: Two Simple Explanations Based on Information in the Stimulus.
AB - Kitaoka's Tomato is a color illusion in which a semitransparent blue-green field
is placed on top of a red object (a tomato). The tomato appears red even though
the pixels would appear green if viewed in isolation. We show that this
phenomenon can be explained by a high-pass filter and by histogram equalization.
The results suggest that this illusion does not require complex inferences about
color constancy; rather, the tomato's red is available in the physical stimulus
at the appropriate spatial scale and dynamic range.
PMID- 29344333
TI - Inverting the Facing-the-Viewer Bias for Biological Motion Stimuli.
AB - Depth-ambiguous point-light walkers are most frequently seen as facing-the-viewer
(FTV). It has been argued that the FTV bias depends on recognising the stimulus
as a person. Accordingly, reducing the social relevance of biological motion by
presenting stimuli upside down has been shown to reduce FTV bias. Here, we
replicated the experiment that reported this finding and added stick figure
walkers to the task in order to assess the effect of explicit shape information
on facing bias for inverted figures. We measured the FTV bias for upright and
inverted stick figure walkers and point-light walkers presented in different
azimuth orientations. Inversion of the stimuli did not reduce facing direction
judgements to chance levels. In fact, we observed a significant facing away bias
in the inverted stimulus conditions. In addition, we found no difference in the
pattern of data between stick figure and point-light walkers. Although the
results are broadly consistent with previous findings, we do not conclude that
inverting biological motion simply negates the FTV bias; rather, inversion causes
stimuli to be seen facing away from the viewer more often than not. The results
support the interpretation that primarily low-level visual processes are
responsible for the biases produced by both upright and inverted stimuli.
PMID- 29344335
TI - Glycemic control among primary care patients with type 2 diabetes mellitus in the
Gaza Strip, Palestine.
AB - Aim: In this study, we aimed to assess the level of good glycemic control, to
determine association between adherence to antidiabetic medications and
glycosylated hemoglobin (HbA1c) and to examine factors influencing good glycemic
control. Materials and methods: A cross-sectional design was employed among 369
patients with type 2 diabetes mellitus (T2DM) from four Ministry of Health health
centers in 2016. A sample of 3 ml blood was taken to measure the HbA1c, and
patients were asked to fill out a pretested questionnaire. Univariate and
multivariate logistic regressions, to identify independent factors associated
with good glycemic control, were conducted using SPSS software version 22 (IBM
Corp, Armonk, NY, USA). Results: Mean [+/-standard deviation (SD)] of HbA1c was
8.97 (2.02) and one fifth of patients had good glycemic control (HbA1c ? 7%).
Factors associated with good glycemic control were: older age [odds ratio (OR) =
0.96, 95% confidence interval (CI): 0.933-0.988), high medication adherence (OR:
2.757, 95% CI: 1.308-4.693), and better health literacy (OR= 2.124, 95% CI: 1.917
4.921). Duration of diabetes mellitus (DM > 7 years) was inversely related to
good glycemic control (OR = 2.255, 95% CI: 1.189-4.276). Conclusion: Our study
showed that glycemic control was suboptimal, and factors associated with that
were: older age, high medication adherence, and better health literacy. Knowledge
of these factors could be an entry toward helping patients and targeting
interventions to improve glycemic control and prevent diabetes-related
complications.
PMID- 29344334
TI - Collective adhesion and displacement of retinal progenitor cells upon
extracellular matrix substrates of transplantable biomaterials.
AB - Strategies to replace retinal photoreceptors lost to damage or disease rely upon
the migration of replacement cells transplanted into sub-retinal spaces. A
significant obstacle to the advancement of cell transplantation for retinal
repair is the limited migration of transplanted cells into host retina. In this
work, we examine the adhesion and displacement responses of retinal progenitor
cells on extracellular matrix substrates found in retina as well as widely used
in the design and preparation of transplantable scaffolds. The data illustrate
that retinal progenitor cells exhibit unique adhesive and displacement dynamics
in response to poly-l-lysine, fibronectin, laminin, hyaluronic acid, and
Matrigel. These findings suggest that transplantable biomaterials can be designed
to improve cell integration by incorporating extracellular matrix substrates that
affect the migratory behaviors of replacement cells.
PMID- 29344336
TI - Treating nonalcoholic fatty liver disease in patients with type 2 diabetes
mellitus: a review of efficacy and safety.
AB - Objective: To review current literature for the efficacy and safety of treatment
for nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes
mellitus (T2DM). Data sources: A PubMed literature search from January 1990 to
June 2017 was conducted using the search terms nonalcoholic fatty liver disease,
diabetes mellitus, type 2, therapy, treatment, treat, therapeutics, nonalcoholic
fatty liver, nonalcoholic hepatosteatosis, NASH, NAFLD, metformin, and statin.
Bibliographies of chosen articles were reviewed. Study selection and data
extraction: Relevant articles on metformin, thiazolidinediones (TZD), glucagon
like peptide-1 receptor agonists (GLP-1 RA), and statins for the treatment of
NAFLD which included patients with T2DM were reviewed. A total of 23 relevant
studies were found and included randomized controlled, observational, and open
label designs, as well as three meta-analyses. Data synthesis: Metformin combined
with weight loss provides a modest improvement in steatosis and no improvement in
fibrosis in patients with NAFLD and T2DM. TZDs showed positive results on
fibrosis and resolution of NASH but at least half of patients studied were
nonresponders. GLP-1 RAs also showed favorable results on reductions in
transaminases and steatosis and improvements in insulin sensitivity and weight
loss but lack efficacy data for resolution of NASH or improvement in fibrosis
scores. Statins showed favorable results on reductions in transaminases but mixed
results for improvement in steatosis and fibrosis scores. Conclusion: All
reviewed treatment options are safe for management of NAFLD in patients with T2DM
but long-term histological improvements are minimal. TZDs are efficacious for
resolution of NASH and improvements in fibrosis but long-term use is required to
maintain these results.
PMID- 29344337
TI - Financial burden of diabetic foot ulcers to world: a progressive topic to discuss
always.
AB - Diabetic foot complications are the most common occurring problems throughout the
globe, resulting in devastating economic crises for the patients, families and
society. Diabetic foot ulcers (DFUs) have a neuropathic origin with a progressive
prevalence rate in developing countries compared with developed countries among
diabetes mellitus patients. Diabetic patients that are of greatest risk of ulcers
may easily be diagnosed with foot examination. Economic burden may be carefully
examined. The budget costing must include both the clinical and social impact of
the patients.
PMID- 29344338
TI - Current best practice in the management of Turner syndrome.
AB - Turner syndrome (TS) is characterized by partial or complete loss of the second X
chromosome in phenotypic females resulting in a constellation of clinical
findings that may include lymphedema, cardiac anomalies, short stature, primary
ovarian failure and neurocognitive difficulties. Optimizing health care delivery
is important to enable these individuals achieve their full potential. We review
the current best practice management recommendations for individuals with TS
focusing on the latest consensus opinion in regard to genetic diagnosis,
treatment of short stature, estrogen supplementation, addressing psychosocial
issues, as well screening for other comorbidities. A multidisciplinary approach
and a well-planned transition to adult follow-up care will improve health care
delivery significantly for this population.
PMID- 29344339
TI - Clozapine discontinuation in early schizophrenia: a retrospective case note
review of patients under an early intervention service.
AB - Aim: Research in patients with treatment-resistant schizophrenia has demonstrated
that clozapine discontinuation is associated with poor outcomes. There is,
however, a paucity of research investigating the impact of clozapine
discontinuation specifically in younger patients with more recent onset
schizophrenia. A case note review was therefore conducted to ascertain medium
term prognoses in patients with treatment-resistant schizophrenia under an early
intervention service (EIS) following clozapine discontinuation. Methods: The case
notes of 25 patients under the care of Birmingham EIS who discontinued clozapine
were examined retrospectively. Reasons for discontinuation were recorded.
Clinical outcomes including total duration of inpatient or home treatment
admission, antipsychotic dose, number of alternative antipsychotics prescribed
and adverse events were recorded for both the year before and the year after
stopping clozapine. Statistical comparisons of pre- and post-discontinuation
clinical outcomes determined whether discontinuation had negative effects.
Results: There was no significant difference between the pre- and post
discontinuation clinical status following clozapine discontinuation. More than
half (56%) of patients remained stable after stopping clozapine. Mean inpatient
or home treatment stay rose from 29.7 to 62.6 days (p = 0.155), total
antipsychotic dose from 50.1% of British National Formulary (BNF) limits to 60.5%
(p = 0.627), number of alternative antipsychotics prescribed from 1.28 to 1.80 (p
= 0.186), number of hospital/home treatment episodes from 0.20 to 0.44 (p =
0.083) and number of adverse events from 0 to 0.20 (p = 0.059). Non-compliance
was the main reason for discontinuation (44%, n = 11). Conclusions: This is the
first clozapine discontinuation study specifically considering EIS patients.
Discontinuation did not lead to significant effects on 1 year outcomes, though
the study is underpowered. These findings may be used to inform future
prospective cohort discontinuation studies.
PMID- 29344340
TI - Assessment and management of sexual dysfunction in the context of depression.
AB - Sexual dysfunction (SD) is pervasive and underreported, and its effects on
quality of life are underestimated. Due in part to its bidirectional relationship
with depression, SD can be difficult to diagnose; it is also a common side effect
of many antidepressants, leading to treatment noncompliance. While physicians
often count on patients to spontaneously report SD, treatment is optimized when
the clinician instead performs a thorough assessment of sexual functioning before
and during drug therapy using a standardized questionnaire such as the Arizona
Sexual Experiences Scale (ASEX). Separating the effects of the disorder from
those of medications is challenging; we present a concise, evidence-based
schematic to assist physicians in minimizing treatment-emergent sexual
dysfunction (TESD) while treating depression. Vascular, hormonal, neurogenic, and
pharmacological factors should be considered when a patient presents with SD. We
also recommend that physicians obtain patient information about baseline and
historical sexual functioning before prescribing a drug that may lead to SD and
follow up accordingly. When the goal is to treat depression while attenuating the
risk of sexual symptoms, physicians may wish to consider agomelatine, bupropion,
desvenlafaxine, moclobemide, trazodone, vilazodone, and vortioxetine.
PMID- 29344341
TI - Treatment of adult ADHD: a clinical perspective.
AB - Adult attention deficit/hyperactivity disorder (ADHD) has moved from the blurred
edge of clinical focus to clear recognition as a prevalent and significant
disorder in its own right. It is a relatively common comorbidity which if
identified and treated may open the door to better outcomes for hard-to-treat
patients. Conversely, failure to identify and treat adult ADHD is linked to
negative outcomes. The recognition of the importance of adult ADHD in a subset of
our patients challenges us to overcome our anxiety about this diagnosis and
prevent the societal marginalization of vulnerable patients. Adult ADHD responds
well to integrated pharmacological and psychotherapeutic intervention. Its
treatment responsiveness reduces disability and allows the comorbidity which is
typically present to be addressed. Mastering this challenge can make the
diagnosis and treatment of adult ADHD a rewarding experience.
PMID- 29344343
TI - The role of selective serotonin reuptake inhibitors in preventing relapse of
major depressive disorder.
AB - The objective of this review was to evaluate the efficacy of selective serotonin
reuptake inhibitors (SSRIs) and SSRIs compared with other treatment modalities in
preventing relapse after an episode of major depressive disorder (MDD). An Ovid
MEDLINE and PsycINFO search (from 1987 to August 2017) was conducted using the
following terms: selective serotonin reuptake inhibitors, antidepressants,
depression, prevention, prophylaxis, relapse and MDD. Using predefined criteria,
two authors independently selected and reached consensus on the included studies.
Sixteen articles met the criteria: 10 compared the relapse rate of selective
SSRIs with placebo or other SSRIs; one discussed the effectiveness of SSRIs plus
psychotherapy, two compared SSRI versus tricyclic antidepressants (TCAs), two
were mainly composed of TCAs plus psychotherapy, and one compared SSRIs and
serotonin norepinephrine reuptake inhibitors (SNRIs). According to the included
studies, the relapse risk in adults was lower when SSRIs were combined with
psychotherapy. Results comparing SSRIs and SNRIs were inconclusive. TCAs may be
equally as effective as SSRIs. Atypical antidepressants (mirtazapine and St
John's Wort) had no significant difference in efficacy and remission rates
compared with SSRIs. Escitalopram appeared to fare better in efficacy than other
SSRIs, owing to a higher prophylactic efficacy and lower side effects; however,
according to the current data, this difference was not significant. To conclude,
this review provides evidence that continuing SSRIs for 1 year reduces risk of
MDD and relapse. Furthermore, the combination of SSRIs and cognitive behavioural
therapy may effectively reduce relapse. Escitalopram appeared to yield better
results and fewer side effects than did other SSRIs or SNRIs. The effectiveness
in reducing relapse of SSRIs was similar to that of TCAs and atypical
antidepressants.
PMID- 29344344
TI - Acetylcholinesterase inhibitors in treatment-resistant psychotic depression.
AB - Dopamine receptor antagonists can be effective in psychotic depression but
response is not assured. Visual hallucinations may arise from a dysregulation of
brain cholinergic systems and acetylcholinesterase inhibitors (AChEIs) can treat
such hallucinations in dementia with Lewy bodies (DLB). AChEIs have been used in
schizophrenia with some success but their efficacy and tolerability in psychotic
depression is unclear. This striking case illustrates AChEIs specifically
targeting multimodal hallucinations in treatment-resistant depression. To our
knowledge it is the first case report to do so. It highlights the value of
delineating psychopathology when considering novel interventions. This case also
shows the idiosyncratic nature of side effects and the importance of pursuing
different drugs within class.
PMID- 29344342
TI - Frontotemporal dementia: latest evidence and clinical implications.
AB - Background: Frontotemporal dementia (FTD) describes a cluster of neurocognitive
syndromes that present with impairment of executive functioning, changes in
behavior, and a decrease in language proficiency. FTD is the second most common
form of dementia in those younger than 65 years and is expected to increase in
prevalence as the population ages. This goal in our review is to describe
advances in the understanding of neurobiological pathology, classification,
assessment, and treatment of FTD syndromes. Methods: PubMed was searched to
obtain reviews and studies that pertain to advancements in genetics,
neurobiology, neuroimaging, classification, and treatment of FTD syndromes.
Articles were chosen with a predilection to more recent preclinical/clinical
trials and systematic reviews. Results: Recent reviews and trials indicate a
significant advancement in the understanding of molecular and neurobiological
clinical correlates to variants of FTD. Genetic and histopathologic markers have
only recently been discovered in the past decade. Current therapeutic modalities
are limited, with most studies reporting improvement in symptoms with
nonpharmacological interventions. However, a small number of studies have
reported improvement of behavioral symptoms with selective serotonin reuptake
inhibitor (SSRI) treatment. Stimulants may help with disinhibition, apathy, and
risk-taking behavior. Memantine and cholinesterase inhibitors have not
demonstrated efficacy in ameliorating FTD symptoms. Antipsychotics have been used
to treat agitation and psychosis, but safety concerns and side effect profiles
limit utilization in the general FTD population. Nevertheless, recent
breakthroughs in the understanding of FTD pathology have led to developments in
pharmacological interventions that focus on producing treatments with autoimmune,
genetic, and molecular targets. Conclusion: FTD is an underdiagnosed group of
neurological syndromes comprising multiple variants with distinct neurobiological
profiles and presentations. Recent advances suggest there is an array of
potential novel therapeutic targets, although data concerning their effectiveness
are still preliminary or preclinical. Further studies are required to develop
pharmacological interventions, as there are currently no US Food and Drug
administration approved treatments to manage FTD syndromes.
PMID- 29344345
TI - When the drugs don't work: treatment-resistant schizophrenia, serotonin and
serendipity.
AB - Treatment-resistant schizophrenia is a serious clinical problem. We adopt a
systems-level approach positing a greater role for cognitive control mechanisms
in the development of psychotic symptoms and illustrate the clinical application
of this via a case report of treatment-resistant patients treated successfully
with adjunct pro-cognitive serotonergic medication.
PMID- 29344346
TI - Characterization and selective incorporation of small non-coding RNAs in non
small cell lung cancer extracellular vesicles.
AB - Background: Extracellular vesicles (EVs) play important roles in intercellular
communication through the delivery of their cargoes, which include proteins,
lipids, and RNAs. Increasingly, multiple studies have reported the association
between EV small non-coding RNAs and cancer, due to their regulatory functions in
gene expression. Hence, analysis of the features of small non-coding RNA
expression and their incorporation into EVs is important for cancer research.
Results: We performed deep sequencing to investigate the expression of small RNAs
in plasma EVs from lung adenocarcinoma (ADC) patients, lung squamous cell
carcinoma (SQCC) patients, and healthy controls. Then, eighteen differently
expressed miRNAs in plasma EVs was validated by QRT-PCR. The small RNA expression
profiles of plasma EVs were different among lung ADC, SQCC patients, and healthy
controls. And many small RNAs, including 5' YRNA hY4-derived fragments, miR-451a,
miR-122-5p, miR-20a-5p, miR-20b-5p, miR-30b-5p, and miR-665, were significantly
upregulated in non-small cell lung cancer (NSCLC) EVs. And the cell viability
assays indicated that hY4-derived fragments inhibited the proliferation of lung
cancer cell A549. By comparing the cellular and EV expression levels of six
miRNAs in NSCLC cells, we found that miR-451a and miR-122-5p were significantly
downregulated in NSCLC cell lysates, while significantly upregulated in NSCLC
EVs. Conclusions: The differently expressed EV small RNAs may serve as potential
circulating biomarkers for the diagnosis of NSCLC. Particularly, YRNA hY4-derived
fragments can serve as a novel class of biomarkers, which function as tumor
suppressors in NSCLC. Additionally, miR-451a and miR-122-5p may be sorted into
NSCLC EVs in a selective manner.
PMID- 29333228
TI - Quantification of polysaccharides fixed to Gram stained slides using lactophenol
cotton blue and digital image processing.
AB - Indigo rings and circles emerged when I added the non-specific polysaccharide
stain lactophenol cotton blue to Gram stained slides. I attribute the dark blue
staining to the presence of capsular polysaccharides and bacterial slime
associated with clumps of Gram-negative bacteria. Since all bacterial cells are
glycosylated and concentrate polysaccharides from the media, the majority of
cells stain light blue. The contrast between dark and light staining is
sufficient to enable a digital image processing thresholding technique to be
quantitative with little background noise. Prior to the addition of lactophenol
cotton blue, the Gram-stained slides appeared unremarkable, lacking ubiquitous
clumps or stained polysaccharides. Adding lactophenol cotton blue to Gram
stained slides is a quick and inexpensive way to screen cell cultures for
bacterial slime, clumps and biofilms that are invisible using the Gram stain
alone.
PMID- 29344347
TI - Epigenetic alterations in TRAMP mice: epigenome DNA methylation profiling using
MeDIP-seq.
AB - Purpose: We investigated the genomic DNA methylation profile of prostate cancer
in transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer model and to
analyze the crosstalk among targeted genes and the related functional pathways.
Methods: Prostate DNA samples from 24-week-old TRAMP and C57BL/6 male mice were
isolated. The DNA methylation profiles were analyzed by methylated DNA
immunoprecipitation (MeDIP) followed by next-generation sequencing (MeDIP-seq).
Canonical pathways, diseases and function and network analyses of the different
samples were then performed using the Ingenuity(r) Pathway Analysis (IPA)
software. Some target genes with significant difference in methylation were
selected for validation using methylation specific primers (MSP) and qPCR.
Results: TRAMP mice undergo extensive aberrant CpG hyper- and hypo-methylation.
There were 2147 genes with a significant (log2-change >= 2) change in CpG
methylation between the two groups, as mapped by the IPA software. Among these
genes, the methylation of 1105 and 1042 genes was significantly decreased and
increased, respectively, in TRAMP prostate tumors. The top associated disease
identified by IPA was adenocarcinoma; however, the cAMP response element-binding
protein (CREB)-, histone deacetylase 2 (HDAC2)-, glutathione S-transferase pi
(GSTP1)- and polyubiquitin-C (UBC)-related pathways showed significantly altered
methylation profiles based on the canonical pathway and network analyses. MSP and
qPCR results of genes of interests corroborated with MeDIP-seq findings.
Conclusions: This is the first MeDIP-seq with IPA analysis of the TRAMP model to
provide novel insight into the genome-wide methylation profile of prostate
cancer. Studies on epigenetics, such as DNA methylation, will potentially provide
novel avenues and strategies for further development of biomarkers targeted for
treatment and prevention approaches for prostate cancer.
PMID- 29333229
TI - Predicted protein interactions of IFITMs may shed light on mechanisms of Zika
virus-induced microcephaly and host invasion.
AB - After the first reported case of Zika virus (ZIKV) in Brazil, in 2015, a
significant increase in the reported cases of microcephaly was observed.
Microcephaly is a neurological condition in which the infant's head is
significantly smaller with complications in brain development. Recently, two
small membrane-associated interferon-inducible transmembrane proteins (IFITM1 and
IFITM3) have been shown to repress members of the flaviviridae family which
includes ZIKV. However, the exact mechanisms leading to the inhibition of the
virus are yet unknown. Here, we assembled an interactome of IFITM1 and IFITM3
with known protein-protein interactions (PPIs) collected from publicly available
databases and novel PPIs predicted using the High-confidence Protein-Protein
Interaction Prediction (HiPPIP) model. We analyzed the functional and pathway
associations of the interacting proteins, and found that there are several
immunity pathways (toll-like receptor signaling, cd28 signaling in T-helper
cells, crosstalk between dendritic cells and natural killer cells), neuronal
pathways (axonal guidance signaling, neural tube closure and actin cytoskeleton
signaling) and developmental pathways (neural tube closure, embryonic skeletal
system development) that are associated with these interactors. Our novel PPIs
associate cilia dysfunction in ependymal cells to microcephaly, and may also shed
light on potential targets of ZIKV for host invasion by immunosuppression and
cytoskeletal rearrangements. These results could help direct future research in
elucidating the mechanisms underlying host defense to ZIKV and other
flaviviruses.
PMID- 29344350
TI - The sensitivity of the human thirst response to changes in plasma osmolality: a
systematic review.
AB - Background: Dehydration is highly prevalent and is associated with adverse
cardiovascular and renal events. Clinical assessment of dehydration lacks
sensitivity. Perhaps a patient's thirst can provide an accurate guide to fluid
therapy. This systematic review examines the sensitivity of thirst in responding
to changes in plasma osmolality in participants of any age with no condition
directly effecting their sense of thirst. Methods: Medline and EMBASE were
searched up to June 2017. Inclusion criteria were all studies reporting the
plasma osmolality threshold for the sensation of thirst. Results: A total of 12
trials were included that assessed thirst intensity on a visual analogue scale,
as a function of plasma osmolality (pOsm), and employed linear regression to
define the thirst threshold. This included 167 participants, both healthy
controls and those with a range of pathologies, with a mean age of 41 (20-78)
years.The value +/-95% CI for the pOsm threshold for thirst sensation was found
to be 285.23 +/- 1.29 mOsm/kg. Above this threshold, thirst intensity as a
function of pOsm had a mean +/- SEM slope of 0.54 +/- 0.07 cm/mOsm/kg. The mean
+/- 95% CI vasopressin release threshold was very similar to that of thirst,
being 284.3 +/- 0.71 mOsm/kg.Heterogeneity across studies can be accounted for by
subtle variation in experimental protocol and data handling. Conclusion: The
thresholds for thirst activation and vasopressin release lie in the middle of the
normal range of plasma osmolality. Thirst increases linearly as pOsm rises. Thus,
osmotically balanced fluid administered as per a patient's sensation of thirst
should result in a plasma osmolality within the normal range. This work received
no funding.
PMID- 29344351
TI - Endemic carbapenem-nonsusceptible Acinetobacter baumannii-calcoaceticus complex
in intensive care units of the national referral hospital in Jakarta, Indonesia.
AB - Background: Carbapenem-nonsusceptible A. baumannii-calcoaceticus complex have
emerged worldwide, but the epidemiology in Indonesian hospitals has not been
studied. Methods: A prospective observational study was performed on the
intensive care units (ICUs) of the national referral hospital in Jakarta
Indonesia, in 2013 and 2014. All consecutive adult patients admitted and
hospitalized for >48 h in ICUs were included. Basic and clinical data at
admission were recorded. Carbapenem-nonsusceptible A. baumannii-calcoaceticus
complex from clinical cultures and standardized screening were included.
Environmental niches and healthcare workers (HCWs) were also screened. PCR was
used to detect carbapenemase genes, and Raman spectroscopy as well as multilocus
sequence typing (MLST) for typing. Results: Of 412 included patients, 69 (16.7%)
carried carbapenem-nonsusceptible A. baumannii-calcoaceticus complex on
admission, and 89 (25.9%) became positive during ICU stay. The acquisition rate
was 43 per 1000 patient-days at risk. Six isolates were cultured from environment
and one from a HCW. Acquisition of carbapenem-nonsusceptible A. baumannii
calcoaceticus complex was associated with longer ICU stay (median interquartile
range [IQR]: 11 days [5-18], adjusted hazard ratio [aHR]: 2.56 [99% confidence
interval (CI):1.76-3.70]), but not with mortality (adjusted odds ratio: 1.59
[99%CI: 0.74-3.40] at the chosen level of significance). The blaOXA-23-like gene
was detected in 292/318 (91.8%) isolates, including isolates from the environment
and HCW. Typing revealed five major clusters. Sequence types (ST)195, ST208,
ST218, ST642 as well as new STs were found. The dominant clone consisted of
isolates from patients and environment throughout the study period. Conclusions:
Carbapenem-nonsusceptible A. baumannii-calcoaceticus complex are endemic in this
setting. Prevention requires source control and limiting transmission of strains.
Trial registration: The study was retrospectively registered at
www.trialregister.nl (No:5541). Candidate number: 23,527, NTR number: NTR5541,
Date registered NTR: 22nd December 2015.
PMID- 29344352
TI - The use of feed-grade amino acids in lactating sow diets.
AB - Background: The use of feed grade amino acids can reduce the cost of lactation
feed. With changing genetics, increasing feed costs, and higher number of pigs
weaned with heavier wean weights further evaluation of higher inclusion levels of
feed-grade amino acid in lactation diets than previously published is warranted.
Two experiments (Exp.) were conducted to determine the optimal inclusion level of
L-lysine HCl to be included in swine lactation diets while digestible lysine
levels remain constant across dietary treatments and allowing feed grade amino
acids to be added to the diet to maintain dietary ratios relative to lysine to
maximize litter growth rate and sow reproductive performance. Furthermore, the
studies were to evaluate minimal amino acid ratios relative to lysine that allows
for optimal litter growth rate and sow reproductive performance. Results: Exp. 1:
Increasing L-lysine HCl resulted in similar gilt feed intake, litter, and
reproductive performance. Average litter gain from birth to weaning was 2.51,
2.49, 2.59, 2.43, and 2.65 kg/d when gilts were fed 0.00, 0.075, 0.150, 0.225,
and 0.30% L-lysine HCl, respectively. Exp. 2: The average litter gain from birth
to weaning was 2.68, 2.73, 2.67, 2.70, and 2.64 kg/d (P < 0.70) when sows were
fed 0.1, 0.2, 0.3, 0.4, and 0.4% L-lysine HCl plus valine, respectively. No other
differences among dietary treatments were observed. Conclusions: Collectively,
these studies demonstrate corn-soybean meal based lactation diets formulated with
a constant SID lysine content for all parities containing up to 0.40% L-lysine
HCl with only supplemental feed grade threonine and a methionine source have no
detrimental effect on litter growth rate and subsequent total born.
PMID- 29344353
TI - Effects of TNF receptor blockade on in vitro cell survival and response to
negative energy balance in dairy cattle.
AB - Background: Associative data and some controlled studies suggest that the
inflammatory cytokine tumor necrosis factor (TNF) alpha can induce fatty liver in
dairy cattle. However, research demonstrating that TNFalpha is a necessary
component in the etiology of bovine fatty liver is lacking. The aim of this work
was to evaluate whether blocking TNFalpha signaling with a synthetic cyclic
peptide (TNF receptor loop peptide; TRLP) would improve liver metabolic function
and reduce triglyceride accumulation during feed restriction. Results: Capability
of TRLP to inhibit TNFalpha signaling was confirmed on primary bovine hepatocytes
treated with recombinant bovine TNFalpha and 4 doses of TRLP (0, 1, 10, 50
MUmol/L) over 24 h. Next, 4 lactating Holstein cows (parity 1.4 +/- 0.5, 433 +/-
131 d in milk) in an incomplete Latin rectangle design (3 * 2) were
subcutaneously administered with different TRLP doses (0, 1.5, 3.0 mg/kg BW)
every 4 h for 24 h, followed by an intravenous injection of TNFalpha (5 MUg/kg
BW). Before and for 2 h after TNFalpha injection, TRLP decreased plasma non
esterified fatty acid (NEFA) concentration (P <= 0.05), suggesting an altered
metabolic response to inflammation. Finally, 10 non-pregnant, non-lactating
Holstein cows (3.9 +/- 1.1 yr of age) were randomly assigned to treatments:
control (carrier: 57% DMSO in PBS) or TRLP (1.75 mg TRLP /kg BW per day).
Treatments were administrated every 4 h for 7 d by subcutaneous injection to feed
restricted cows fed 30% of maintenance energy requirements. Daily blood samples
were analyzed for glucose, insulin, beta-hydroxybutyrate, NEFA, and haptoglobin
concentrations, with no treatment effects detected. On d 7, cows completed a
glucose tolerance test (GTT) by i.v. administration of a dextrose bolus (300 mg
glucose/kg BW). Glucose, insulin, and NEFA responses failed to demonstrate any
significant effect of treatment during the GTT. However, plasma and liver
analyses were not indicative of dramatic lipolysis or hepatic lipidosis,
suggesting that the feed restriction protocol failed to induce the metabolic
state of interest. Injection site inflammation, assessed by a scorer blinded to
treatment, was enhanced by TRLP compared to control. Conclusions: Although the
TRLP inhibited bovine TNFalpha signaling and altered responses to i.v.
administration of TNFalpha, repeated use over 7 d caused apparent local allergic
responses and it failed to alter metabolism during a feed restriction-induced
negative energy balance. Although responses to feed restriction seemed atypical
in this study, side effects of TRLP argue against its future use as a tool for
investigating the role of inflammation in metabolic impacts of negative energy
balance.
PMID- 29344354
TI - A study on the implementation fidelity of the performance-based financing policy
in Burkina Faso after 12 months.
AB - Background: Performance-based financing (PBF) in the health sector has recently
gained momentum in low- and middle-income countries (LMICs) as one of the ways
forward for achieving Universal Health Coverage. The major principle underlying
PBF is that health centers are remunerated based on the quantity and quality of
services they provide. PBF has been operating in Burkina Faso since 2011, and as
a pilot project since 2014 in 15 health districts randomly assigned into four
different models, before an eventual scale-up. Despite the need for expeditious
documentation of the impact of PBF, caution is advised to avoid adopting hasty
conclusions. Above all, it is crucial to understand why and how an impact is
produced or not. Our implementation fidelity study approached this inquiry by
comparing, after 12 months of operation, the activities implemented against what
was planned initially and will make it possible later to establish links with the
policy's impacts. Methods: Our study compared, in 21 health centers from three
health districts, the implementation of activities that were core to the process
in terms of content, coverage, and temporality. Data were collected through
document analysis, as well as from individual interviews and focus groups with
key informants. Results: In the first year of implementation, solid foundations
were put in place for the intervention. Even so, implementation deficiencies and
delays were observed with respect to certain performance auditing procedures, as
well as in payments of PBF subsidies, which compromised the incentive-based
rationale to some extent. Conclusion: Over next months, efforts should be made to
adjust the intervention more closely to context and to the original planning.
PMID- 29344355
TI - Impact of an antifungal stewardship intervention on optimization of candidemia
management.
AB - Background: Candidemia represents a leading cause of healthcare-associated
bloodstream infections with significant morbidity and mortality. Previous studies
have demonstrated that comprehensive care bundles improve candidemia management
but are time-consuming. Objective: To determine the impact of a one-time targeted
candidemia intervention on time to initiation of adequate therapy compared to
standard of care. Methods: This Institutional Review Board (IRB)-approved, quasi
experiment evaluated a targeted candidemia intervention involving a single phone
call to the primary team providing recommendations for care. Daily follow-up was
provided by the infectious diseases (ID) consult service. Two time periods were
evaluated: pre-intervention (01 August 2012 to 31 July 2014) and post
intervention (01 October 2014 to 30 September 2016). The primary endpoint was
time to adequate antifungal therapy (TTx) in the business hours (6 a.m. to 6 p.m.
Monday through Friday) population (BHP). Secondary endpoints were TTx in the
total population as well as infection-related length of stay (IF-LOS) and
compliance with quality indicators (composite endpoint: ophthalmology (OPH)
consult, repeat cultures, and ?14 days of adequate therapy). Results: In all, 117
patients were included (pre-intervention = 50, post-intervention = 67, BHP = 51).
TTx decreased from 2 h 57 m to 2 h 12 m (p = 0.094) in the BHP and 3 h 30 m to 2
h 9 m (p = 0.021) in the total population. There was no difference in IF-LOS (p =
0.797), compliance with quality indicators (p = 0.343), or in-hospital mortality
(p = 0.761). Post-intervention, there were more ID and OPH consults (p < 0.001).
Conclusions: Our one-time candidemia intervention did not statistically decrease
time to adequate therapy in the BHP, but did in the total population. No
differences were found for other clinical outcomes, except increases in ID and
OPH consults. Further studies are needed to examine whether a one-time
intervention is non-inferior to a more comprehensive care bundle.
PMID- 29344356
TI - Risk factors and outcomes for multidrug-resistant Gram-negative bacilli
bacteremia.
AB - Background: The incidence of multidrug-resistant (MDR) organisms is increasing
along with mortality. Identifying risk factors for the development of MDR Gram
negative bacilli (GNB) bacteremia could greatly impact patient care and
management. Methods: Data from the electronic health record of patients with GNB
over 13-month period were collected at a single university medical center.
Baseline demographic data, risk factor, microbiological data, recurrence of
bacteremia, and mortality were recorded. Results: A total of 177 patients were
included in the analysis. MDR GNB occurred in 46 patients (26%). The mortality
rate in the MDR group was 34.8% compared to 13.7% in non-MDR group (p = 0.002).
In multivariate analysis, diabetes mellitus [DM; odds ratio (OR): 2.8, 95%
confidence interval (CI): 1-4.88], previous antibiotic use (OR: 2.93, 95% CI:
1.25-6.87), and urinary catheter as a source of infection (OR 5.96, 95% CI: 1.78
19.94) were significant risk factors for the development of MDR GNB. In addition,
end-stage liver disease (OR: 3.64, 95% CI: 1.07-12.3), solid organ malignancy
(OR: 3.64, 95% CI: 1.25-10.56), intra-abdominal source of infection (OR: 3.66,
95% CI: 1.14-11.73), inappropriate empiric antibiotics (OR 7.59, 95% CI: 1.68
34.34) and urinary catheter as a source of infection (OR 5.68, 95% CI: 1.37-23.5)
were significant factors for mortality in patients with MDR GNB. Conclusion: Our
study provides important information about the risk factors for the development
of MDR GNB bacteremia and helps prognosticate patient with MDR GNB.
PMID- 29344357
TI - Examining the effectiveness of a cognitive intervention to improve cognitive
function in a population of older adults living with HIV: a pilot study.
AB - Objective: The purpose of this randomized-controlled pilot study was to explore
the effectiveness of a home-based computerized cognitive training intervention in
improving cognitive function in a population of older adults with mild cognitive
impairment who are living with HIV. Methods: In all, 24 participants were
enrolled in this study. All study participants were impaired [defined as Montreal
Cognitive Assessment (MoCA) score < 26]; 12 were randomly assigned to a computer
training intervention group and 12 to a control group. The intervention group
used a home-based computerized cognitive training program for 8 weeks, while the
control group received health-related newsletter via email and follow-up phone
calls. Cognitive function was measured at study entry, immediately post
intervention, and 8 and 16 weeks post intervention. Results: This study achieved
a 92% retention rate, losing two persons from the intervention group.
Participants in the intervention group scored significantly higher on cognitive
testing immediately post intervention compared to the control group: F(1, 19) =
4.92, p = 0.04. The partial Eta squared of 0.32 indicates a small to moderate
effect size. Discussion: Cognitive improvement was seen immediately after the
intervention, and cognitive improvement was still evident 16 weeks post
intervention. Cognitive training could be considered as an option for older
adults with HIV experiencing mild cognitive impairment.
PMID- 29344359
TI - Group schema therapy for eating disorders: study protocol.
AB - Background: The treatment of eating disorders is a difficult endeavor, with only
a relatively small proportion of clients responding to and completing standard
cognitive behavioural therapy (CBT). Given the prevalence of co-morbidity and
complex personality traits in this population, Schema Therapy has been identified
as a potentially viable treatment option. A case series of Group Schema Therapy
for Eating Disorders (ST-E-g) yielded positive findings and the study protocol
outlined in this article aims to extend upon these preliminary findings to
evaluate group Schema Therapy for eating disorders in a larger sample (n = 40).
Methods/design: Participants undergo a two-hour assessment where they complete a
number of standard questionnaires and their diagnostic status is ascertained
using the Eating Disorder Examination. Participants then commence treatment,
which consists of 25 weekly group sessions lasting for 1.5 h and four individual
sessions. Each group consists of five to eight participants and is facilitated by
two therapists, at least one of who is a registered psychologist trained on
schema therapy. The primary outcome in this study is eating disorder symptom
severity. Secondary outcomes include: cognitive schemas, self-objectification,
general quality of life, self-compassion, schema mode presentations, and
Personality Disorder features. Participants complete psychological measures and
questionnaires at pre, post, six-month and 1-year follow-up. Discussion: This
study will expand upon preliminary research into the efficacy of group Schema
Therapy for individuals with eating disorders. If group Schema Therapy is shown
to reduce eating disorder symptoms, it will hold considerable promise as an
intervention option for a group of disorders that is typically difficult to
treat. Trial registration: ACTRN12615001323516. Registered: 2/12/2015
(retrospectively registered, still recruiting).
PMID- 29344358
TI - The global problem of childhood diarrhoeal diseases: emerging strategies in
prevention and management.
AB - Acute diarrhoeal diseases remain a leading cause of global morbidity and
mortality particularly among young children in resource-limited countries. Recent
large studies utilizing case-control design, prospective sampling and more
sensitive and broad diagnostic techniques have shed light on particular pathogens
of importance and highlighted the previously under recognized impact of these
infections on post-acute illness mortality and growth. Vaccination, particularly
against rotavirus, has emerged as a key effective means of preventing significant
morbidity and mortality from childhood diarrhoeal disease. Other candidate
vaccines against leading diarrhoeal pathogens, such as enterotoxigenic
Escherichia coli and Shigella spp., also hold significant promise in further
ameliorating the burden of enteric infections in children. Large studies are also
currently underway evaluating novel and potential easy-to-implement water,
sanitation and hygiene (WASH) preventive strategies. Given the ongoing global
burden of this illness, the paucity of new advances in case management over the
last several decades remains a challenge. The increasing recognition of post
acute illness mortality and growth impairment has highlighted the need for
interventions that go beyond management of dehydration and electrolyte
disturbances. The few trials of novel promising interventions such as probiotics
have mainly been conducted in high-income settings. Trials of antimicrobials have
also been primarily conducted in high-income settings or in travellers from high
income settings. Bloody diarrhoea has been shown to be a poor marker of
potentially treatable bacterial enteritis, and rising antimicrobial resistance
has also made empiric antimicrobial therapy more challenging in many settings.
Novel effective and sustainable interventions and diagnostic strategies are
clearly needed to help improve case management. Diarrhoeal disease and other
enteric infections remain an unmet challenge in global child health. Most
promising recent developments have been focused around preventive measures, in
particular vaccination. Further advances in prevention and case management
including the possible use of targeted antimicrobial treatment are also required
to fully address this critical burden on child health and human potential.
PMID- 29344360
TI - Validity, reliability and Norwegian adaptation of the Stroke-Specific Quality of
Life (SS-QOL) scale.
AB - Background: There is a paucity of stroke-specific instruments to assess health
related quality of life in the Norwegian language. The objective was to examine
the validity and reliability of a Norwegian version of the 12-domain Stroke
Specific Quality of Life scale. Methods: A total of 125 stroke survivors were
prospectively recruited. Questionnaires were administered at 3 months; 36 test
retests were performed at 12 months post stroke. The translation was conducted
according to guidelines. The internal consistency was assessed with Cronbach's
alpha; convergent validity, with item-to-subscale correlations; and test-retest,
with Spearman's correlations. Scaling validity was explored by calculating both
floor and ceiling effects. A priori hypotheses regarding the associations between
the Stroke-Specific Quality of Life domain scores and scores of established
measures were tested. Standard error of measurement was assessed. Results: The
Norwegian version revealed no major changes in back translations. The internal
consistency values of the domains were Cronbach's alpha = 0.79-0.93. Rates of
missing items were small, and the item-to-subscale correlation coefficients
supported convergent validity (0.48-0.87). The observed floor effects were
generally small, whereas the ceiling effects had moderate or high values (16%
63%). Test-retest reliability indicated stability in most domains, with
Spearman's rho = 0.67-0.94 (all p < 0.001), whereas the rho was 0.35 (p < 0.05)
for the 'Vision' domain. Hypothesis testing supported the construct validity of
the scale. Standard error of measurement values for each domain were generated to
indicate the required magnitudes of detectable change. Conclusions: The Norwegian
version of the Stroke-Specific Quality of Life scale is a reliable and valid
instrument with good psychometric properties. It is suited for use in health
research as well as in individual assessments of persons with stroke.
PMID- 29344361
TI - Platelet protein biomarker panel for ovarian cancer diagnosis.
AB - Background: Platelets support cancer growth and spread making platelet proteins
candidates in the search for biomarkers. Methods: Two-dimensional (2D) gel
electrophoresis, Partial Least Squares Discriminant Analysis (PLS-DA), Western
blot, DigiWest. Results: PLS-DA of platelet protein expression in 2D gels
suggested differences between the International Federation of Gynaecology and
Obstetrics (FIGO) stages III-IV of ovarian cancer, compared to benign adnexal
lesions with a sensitivity of 96% and a specificity of 88%. A PLS-DA-based model
correctly predicted 7 out of 8 cases of FIGO stages I-II of ovarian cancer after
verification by western blot. Receiver-operator curve (ROC) analysis indicated a
sensitivity of 83% and specificity of 76% at cut-off >0.5 (area under the curve
(AUC) = 0.831, p < 0.0001) for detecting these cases. Validation on an
independent set of samples by DigiWest with PLS-DA differentiated benign adnexal
lesions and ovarian cancer, FIGO stages III-IV, with a sensitivity of 70% and a
specificity of 83%. Conclusion: We identified a group of platelet protein
biomarker candidates that can quantify the differential expression between
ovarian cancer cases as compared to benign adnexal lesions.
PMID- 29344362
TI - Development of biomarker combinations for postoperative acute kidney injury via
Bayesian model selection in a multicenter cohort study.
AB - Background: Acute kidney injury (AKI) is a frequent complication of cardiac
surgery. We sought prognostic combinations of postoperative biomarkers measured
within 6 h of surgery, potentially in combination with cardiopulmonary bypass
time (to account for the degree of insult to the kidney). We used data from a
large cohort of patients and adapted methods for developing biomarker
combinations to account for the multicenter design of the study. Methods: The
primary endpoint was sustained mild AKI, defined as an increase of 50% or more in
serum creatinine over preoperative levels lasting at least 2 days during the
hospital stay. Severe AKI (secondary endpoint) was defined as a serum creatinine
increase of 100% or more or dialysis during hospitalization. Data were from a
cohort of 1219 adults undergoing cardiac surgery at 6 medical centers; among
these, 117 developed sustained mild AKI and 60 developed severe AKI. We
considered cardiopulmonary bypass time and 22 biomarkers as candidate predictors.
We adapted Bayesian model averaging methods to develop center-adjusted
combinations for sustained mild AKI by (1) maximizing the posterior model
probability and (2) retaining predictors with posterior variable probabilities
above 0.5. We used resampling-based methods to avoid optimistic bias in
evaluating the biomarker combinations. Results: The maximum posterior model
probability combination included plasma N-terminal-pro-B-type natriuretic
peptide, plasma heart-type fatty acid binding protein, and change in serum
creatinine from before to 0-6 h after surgery; the median probability combination
additionally included plasma interleukin-6. The center-adjusted, optimism
corrected AUCs for these combinations were 0.80 (95% CI: 0.78, 0.87) and 0.81
(0.78, 0.87), respectively, for predicting sustained mild AKI, and 0.81 (0.76,
0.90) and 0.83 (0.76, 0.90), respectively, for predicting severe AKI. For these
data, the Bayesian model averaging methods yielded combinations with prognostic
capacity comparable to that achieved by standard frequentist methods but with
more parsimonious models. Conclusions: Pending external validation, the
identified combinations could be used to identify individuals at high risk of AKI
immediately after cardiac surgery and could facilitate clinical trials of
renoprotective agents.
PMID- 29344363
TI - Motile Salmonella serotypes causing high mortality in poultry farms in three
South-Western States of Nigeria.
AB - This study was carried out to identify the Salmonella serotypes causing high
mortality in chickens in Lagos, Ogun and Oyo states, Nigeria. Chickens presented
for postmortem examination during disease outbreaks that were characterised by
high mortality (40 per cent to 80 per cent) in poultry farms in the study area
were examined from January to December, 2013. Samples of the lungs, heart, liver,
spleen, kidneys, proventriculus, intestine and caecum were collected from
suspected cases of salmonellosis, for bacterial culture and identification.
Salmonella isolates were confirmed using PCR and serotyped using the Kauffman
White scheme. Twenty-six day-old pullets were raised to two weeks and inoculated
orally with 0.2 mL of 1*108 colony forming units of Salmonella Zega identified in
the present study to determine their pathogenicity, while another 26 served as
control. The Salmonella serotypes were S Zega (n=13; 35.14 per cent), Salmonella
Kentucky (n=9; 24.32 per cent), Salmonella Herston (n=6; 16.22 per cent),
Salmonella Nima (n=4; 10.81 per cent), Salmonella Telelkebir (n=3; 8.11 per
cent), Salmonella Colindale (n=1; 2.70 per cent) and Salmonella Tshiongwe (n=1;
2.70 per cent). Clinical signs in both natural and experimental infections were
acute (70 per cent) and chronic (30 per cent), and included weakness, anorexia,
yellowish diarrhoea, pasted vents, somnolescence and mortality, while gross
lesions showed marked pulmonary congestion and oedema, necrotic foci in the
myocardium; the liver, spleen and kidneys were markedly enlarged and had
subcapsular multifocal necrosis. There were catarrhal proventriculitis and
enteritis, and haemorrhagic typhlitis. While most of the serotypes identified in
the present study have been isolated from poultry sources from commercial farms
in Nigeria, to the best of the authors' knowledge, they have not been previously
reported to cause high mortality in chickens in the study area.
PMID- 29344364
TI - Novel dry cryotherapy system for cooling the equine digit.
AB - Objectives: Digital cryotherapy is commonly used for laminitis prophylaxis and
treatment. Currently validated methods for distal limb cryotherapy involve wet
application or compression technology. There is a need for a practical,
affordable, dry cryotherapy method that effectively cools the digit. The
objective of this study was to evaluate the hoof wall surface temperatures
(HWSTs) achieved with a novel dry cryotherapy technology. Design: Repeated
measures in vivo experimental study. Setting: Experimental intervention at a
single site. Participants: 6 systemically healthy horses (3 mares, 3 geldings).
Interventions: Cryotherapy was applied to six horses for eight hours with a
commercially available rubber and rubber and welded fabricice boot, which
extended proximally to include the foot and pastern. Reusable malleable cold
therapy packs were secured against the foot and pastern with the three built-in
hook-and-loop fastener panels. Primary and secondary outcome measures: HWST and
pastern surface temperature of the cryotherapy-treated limb, HWST of the control
limb and ambient temperature were recorded every five minutes throughout the
study period. Results: Results were analysed with mixed-effects multivariable
regression analysis. The HWST (median 11.1 degrees C, interquartile range 8.6
degrees C-14.7 degrees C) in the cryotherapy-treated limb was significantly
decreased compared with the control limb (median 29.7 degrees C, interquartile
range 28.9 degrees C-30.4 degrees C) (P<=0.001). Cryotherapy limb HWST reached a
minimum of 6.75 degrees C (median) with an interquartile range of 4.1 degrees C
9.3 degrees C. Minimum HWST was achieved 68 minutes after cryotherapy pack
application. Conclusions: Dry application of cryotherapy significantly reduced
HWST and reached minimums below the therapeutic target of 10 degrees C. This
cryotherapy method might offer an effective alternative for digital cooling.
PMID- 29344365
TI - Arterial pathophysiology and comparison of two devices for pulse wave velocity
assessment in elderly men: the British regional heart study.
AB - Objective: Vascular disease is highly prevalent in the elderly. This study aimed
to evaluate arterial phenotype in elderly men and compare carotid-femoral pulse
wave velocity (cfPWV) assessed by two techniques (Sphygmocor (S)and Vicorder
(V)). Methods: 1722 men (72-92 years), participants in the British Regional Heart
Study, underwent ultrasound assessment of carotid intima-media thickness (cIMT),
carotid distensibility coefficient and presence of carotid plaque. cfPWV and
ankle brachial pressure index (ABPI) were also assessed. 123 men returned for
between visit reproducibility assessments. Results: Good reproducibility was
demonstrated in all measures (Gwet's agreement=0.8 for plaque, intraclass
correlation=0.65 for ABPI and coefficient of variation <13% for all other
measures). Measurements were obtained in >90% of men for all measures except
cfPWV(S) and ABPI. In 1122 men with both cfPWV(V) and cfPWV(S) data, cfPWV(S) was
greater than cfPWV(V) (mean difference=0.23,95%CI 0.10 to 0.37 m/s). cfPWV(V) was
higher at low cfPWV values and cfPWV(S) was higher at high cfPWV values.
Correlation of V transit time (TT) against S carotid and femoral TT demonstrated
that the slope of the regression line for femoral TT was steeper than for carotid
TT, resulting in a proportionally greater subtraction of carotid TT from femoral
TT at higher PWVs. Conclusions: Reproducible, satisfactory quality non-invasive
measurements of vascular phenotype were obtainable in a large proportion of
elderly men. The discrepancy in results between the two PWV measures may partly
be due to the differential impact of subtracting carotid TT when deriving
cfPWV(S) across the clinical PWV range.
PMID- 29344366
TI - Healthcare provider-led interventions to support medication adherence following
ACS: a meta-analysis.
AB - : We conducted a systematic review and meta-analysis to determine the
effectiveness of healthcare provider-led (HCPs) interventions to support
medication adherence in patients with acute coronary syndrome (ACS). A systematic
search of Cochrane Library, Medline, EMBASE, PsycINFO, Web of Science, IPA,
CINAHL, ASSIA, OpenGrey, EthOS, WorldCat and PQDT was undertaken. Interventions
were deemed eligible if they included adult ACS patients, were HCP-led, measured
medication adherence and randomised participants to parallel groups. Intervention
content was coded using the Behaviour Change Technique (BCT) Taxonomy and data
were pooled for analysis using random-effects models. Our search identified 8870
records, of which 27 were eligible (23 primary studies). A meta-analysis (n=9735)
revealed HCP-led interventions increased the odds of medication adherence by 54%
compared to control interventions (k=23, OR 1.54, 95% CI 1.26 to 1.88, I2=57.5%).
After removing outliers, there was a 41% increase in the odds of medication
adherence with moderate heterogeneity (k=21, OR 1.41, 95% CI 1.21 to 1.65,
I2=35.3%). Interventions that included phone contact yielded (k=12, OR 1.63, 95%
CI 1.25 to 2.12, I2=32.0%) a larger effect compared to those delivered
exclusively in person. A total of 32/93 BCTs were identified across interventions
(mean=4.7, SD=2.2) with 'information about health consequences' (BCT 5.1) (19/23)
the most common. HCP-led interventions for ACS patients appear to have a small
positive impact on medication adherence. While we were able to identify BCTs
among interventions, data were insufficient to determine the impact of particular
BCTs on study effectiveness. PROSPERO registration number: CRD42016037706.
PMID- 29344367
TI - Elevated brain natriuretic peptide levels in chronic fatigue syndrome associate
with cardiac dysfunction: a case control study.
AB - Objectives: To explore levels of the brain natriuretic peptide (BNP) and how
these associate with the cardiac abnormalities recently identified in chronic
fatigue syndrome (CFS). Methods: Cardiac magnetic resonance examinations were
performed using 3T Philips Intera Achieva scanner (Best, Netherlands) in CFS
(Fukuda) participants and sedentary controls matched group wise for age and sex.
BNP was also measured by using an enzyme immunoassay in plasma from 42 patients
with CFS and 10 controls. Results: BNP levels were significantly higher in the
CFS cohort compared with the matched controls (P=0.013). When we compared cardiac
volumes (end-diastolic and end-systolic) between those with high BNP levels (BNP
>400 pg/mL) and low BNP (<400 pg/mL), there were significantly lower cardiac
volumes in those with the higher BNP levels in both end-systolic and end
diastolic volumes (P=0.05). There were no relationships between fatigue severity,
length of disease and BNP levels (P=0.2) suggesting that our findings are
unlikely to be related to deconditioning. Conclusion: This study confirms an
association between reduced cardiac volumes and BNP in CFS. Lack of relationship
between length of disease suggests that findings are not secondary to
deconditioning. Further studies are needed to explore the utility of BNP to act
as a stratification paradigm in CFS that directs targeted treatments. Trail
registration number: Registered with NIHR Portfolio CLRN ID 97805.
PMID- 29344368
TI - Inception of the 'endocarditis team' is associated with improved survival in
patients with infective endocarditis who are managed medically: findings from a
before-and-after study.
AB - Objective: Despite improvements in its management, infective endocarditis (IE) is
associated with poor survival. The aim of this study was to evaluate the impact
of a multidisciplinary endocarditis team (ET), including a cardiologist,
microbiologist and a cardiac surgeon, on the outcome of patients with acute IE
according to medical or surgical treatment strategies. Methods: We conducted an
observational before-and-after study of 196 consecutive patients with definite
IE, who were treated at a tertiary reference centre between 2009 and 2015. The
study was divided into two periods: period 1, before the formation of the ET
(n=101), and period 2, after the formation of the ET (n=95). The role of the ET
included regular multidisciplinary team meetings to confirm diagnosis, inform the
type and duration of antibiotic therapy and recommend early surgery, when
indicated, according to European guidelines. Results: The patient demographics
and predisposing conditions for IE were comparable between the two study periods.
In the time period following the introduction of the ET, there was a reduction in
both the time to commencement of IE-specific antibiotic therapy (4.0+/-4.0 days
vs 2.5+/-3.2 days; P=0.004) and the time from suspected IE to surgery (7.8+/-7.3
days vs 5.3+/-4.2 days; P=0.004). A 12-month Kaplan-Meier survival for patients
managed medically was 42.9% in the pre-ET period and 66.7% in the post-ET period
(P=0.03). The involvement of the ET was a significant independent predictor of 1
year survival in patients managed medically (HR 0.24, 95% CI 0.07 to 0.87;
P=0.03). Conclusions: A standardised multidisciplinary team approach may lead to
earlier diagnosis of IE, more appropriate individualised management strategies,
expedited surgery, where indicated, and improved survival in those patients
chosen for medical management, supporting the recent change in guidelines to
recommend the use of a multidisciplinary team in the care of patients with IE.
PMID- 29344369
TI - Rates and risk of arrhythmias in cancer survivors with chemotherapy-induced
cardiomyopathy compared with patients with other cardiomyopathies.
AB - Objectives: There is little information about arrhythmia burden in cancer
survivors with chemotherapy-induced cardiomyopathy (CIC). We hypothesise that the
rates and risk of arrhythmias will be similar in CIC when compared with other non
ischaemic cardiomyopathy (NICMO) aetiologies. Methods: We retrospectively
identified nine patients with CIC and an implantable defibrillator and 18 age and
sex-matched control patients (nine patients with NICMO and nine patients with
ischaemic cardiomyopathy (ICMO)). Rates and odds of arrhythmias were calculated
by type of cardiomyopathy, adjusting for days since implantable cardioverter
defibrillator implantation, history of atrial fibrillation and length of follow
up using logistic regression analysis. Results: Compared with patients with
NICMO, rates and adjusted odds were similar for patients with CIC for atrial
arrhythmias (44.4% vs 33.3%; adjusted OR=1.89; 95% CI0.17 to 21.03; P=0.61), non
sustained ventricular tachycardia (NSVT) (44.4% vs 33.3%; OR=2.10; 95% CI 0.21 to
20.56; P=0.53), and the combined outcome of NSVT, sustained ventricular
tachycardia and/or ventricular fibrillation (44.4% vs 44.4%; OR=2.70; 95% CI 0.25
to 29.48; P=0.42). Conversely, compared with patients with NICMO, patients with
ICMO demonstrated higher rates and adjusted odds of the combined outcome (88.9%
vs 44.4%; OR=28.60; 95% CI 1.26 to 648.2; P=0.04) and NSVT (77.8% vs 33.3%;
OR=8.95; 95% CI 0.90 to 88.94; P=0.06). Conclusions: While tentative based on
sample size, rates of arrhythmias in patients with CIC appear to be similar to
those experienced by patients with other forms of NICMO.
PMID- 29344370
TI - Prevalence and prognostic value of echocardiographic screening for rheumatic
heart disease.
AB - Objective: Rheumatic heart disease (RHD) remains a major health problem in many
low-income and middle-income countries. The use of echocardiographic imaging
suggests that subclinical disease is far more widespread than previously
appreciated, but little is known as to how these mild forms of RHD progress. We
have determined the prevalence of subclinical RHD in a large group of
schoolchildren in Aswan, Egypt and have evaluated its subsequent progression.
Methods: Echocardiographic screening was performed on 3062 randomly selected
schoolchildren, aged 5-15 years, in Aswan, Egypt. Follow-up of children with a
definite or borderline diagnosis of RHD was carried out 48-60 months later to
determine how the valvular abnormalities altered and to evaluate the factors
influencing progression. Results: Sixty children were initially diagnosed with
definite RHD (19.6 per 1000 children) and 35 with borderline disease (11.4 per
1000); most had mitral valve disease. Of the 72 children followed up progression
was documented in 14 children (19.4%) and regression in 30 (41.7%) children. Boys
had lower rates of progression while older children had lower rates of
regression. Functional defects of the valve even in the presence of structural
features were associated with lower rates of progression and higher rates of
regression than structural changes. Conclusions: RHD has a high prevalence in
Egypt. Although a high proportion of the abnormalities originally detected
persisted at follow-up, both progression and regression of valve lesions were
demonstrated.
PMID- 29344371
TI - Accrual monitoring in cardiovascular trials.
AB - Objective: To provide brief guidance on how to design accrual monitoring
activities in a clinical trial protocol. Setting: Two completed clinical trials
that did not achieve the planned sample size, the Cost of Strategies After
Myocardial Infarction (COSTAMI) trial and the Biventricular Pacing After Cardiac
Surgery (BiPACS) trial. Design: A Bayesian monitoring tool, the constant accrual
model, is applied retrospectively to accrual data from each case study to
illustrate how the tool could be used to identify problems with accrual early in
the trial period and to frame the conditions in which the approach can be used in
practice. Results: After 312 days and 155 patients enrolled in the COSTAMI trial,
accrual could be classified as 'off target' on the basis of statistical criteria
outlined in the protocol. As for the BiPACS trial, after 2 years, it was already
evident that the accrual was 'considerably off target'. Conclusions: Prompt
awareness of a high risk of accrual failure could trigger different interventions
to overcome protocol-related, patient-related or investigator-related barriers to
recruitment or ultimately contribute to an early stopping decision due to
recruitment futility.Accrual prediction models should be included as standard
tools for routine monitoring activities in cardiovascular research. Among them,
methods relying on the Bayesian approach are particularly attractive, as they can
naturally update past evidence when actual accrual data becomes available.
PMID- 29344372
TI - Association of high-density lipoprotein cholesterol with non-fatal cardiac and
non-cardiac events: a CANHEART substudy.
AB - Background: Emerging evidence has questioned the role of high-density lipoprotein
cholesterol (HDL-C) as an independent and modifiable risk factor for
cardiovascular disease. We sought to understand the relationship between HDL-C
levels and subsequent non-fatal clinical events. Methods: Individuals without
prior cardiovascular disease or cancer were identified. Outcomes of interest were
classified as non-fatal cardiovascular, cancer and infectious. Sex-stratified,
multivariable, cause-specific Cox proportional hazards models were created. The
reference level HDL-C for both women and men was 51-60 mg/dL. Results: Our cohort
consisted of 631 762 individuals. For cardiovascular events, there was a
consistent inverse relationship, with higher adjusted HRs for the lower HDL-C
strata in both men and women. This relationship was also seen in the composite of
non-cardiovascular outcomes. In women, the HR in the <30 mg/dL HDL-C category was
2.10 (95% CI 1.66 to 2.57) and 1.86 (95% CI 1.27 to 2.72) for cardiovascular and
non-cardiovascular outcomes, respectively; in contrast, in the >90 mg/dL group,
it was 0.87 (95% CI 0.74 to 1.02) and 0.81 (95% CI 0.63 to 1.06). For men, HRs
were 2.02 (95% CI 1.79 to 2.28) and 1.84 (95% CI 1.47 to 2.31) in the <30 mg/dL
HDL-C category for cardiovascular and non-cardiovascular outcomes, respectively,
compared with 0.73 (95% CI 0.53 to 1.00) and 1.07 (95% CI 0.67 to 1.70) in the
>90 mg/dL group. Conclusions: We found an inverse relationship between HDL-C and
a wide spectrum of non-fatal outcomes, suggesting that HDL-C is a heavily
confounded factor that may be a marker of poor overall health, rather than an
independent and modifiable risk factor.
PMID- 29344373
TI - Multianalysis with optical coherence tomography and vasomotion in everolimus
eluting stents and everolimus-eluting biovascular scaffolds: the MOVES trial.
AB - Aims: To compare endothelium-dependent vasomotor function and vascular healing 15
months after implantation of two new-generation drug-eluting stents and
biovascular scaffolds (BVS). Methods and results: A total of 28 patients
previously treated with a SYNERGY stent (bioabsorbable polymer everolimus-eluting
stents (BP-EES)), a PROMUS stent (persistent polymer everolimus-eluting stents
(PP-EES)) or an ABSORB (BVS) underwent control coronary angiography, 15 months
after implantation, coupled with optical coherence tomography imaging and supine
bicycle exercise. Intracoronary nitroglycerin was administered after exercise
testing. Coronary vasomotor response was assessed using quantitative coronary
angiography at rest, during supine bicycle exercise and after nitroglycerin. The
primary end point was the percent change in mean lumen diameter compared with
baseline. Secondary end points were strut coverage and apposition.There were no
significant differences in vasomotor response between the three treatment groups.
Patients with PP-EES showed significant vasoconstriction of the proximal
peristent segment at maximum exercise (P=0.02). BP-EES (2.7%, 95% CI 0 to 5.5)
and BVS (3.2%, 95% CI 0 to 6.7) showed less uncovered struts than PP-EES (12.1%,
95% CI 2.9 to 21.3, P=0.02 and 0.09, respectively). Complete strut apposition was
more frequently seen with BP-EES (99.6%, 95% CI 99.2 to 100) than with BVS
(98.9%, 95% CI 98.2 to 99.6, P=0.04) or PP-EES (95.0%, 95% CI 91.6 to 98.5,
P=0.001). Conclusion: BVS and thin strut BP-EES have a reassuring vasomotion
profile, suggesting minimal endothelial dysfunction 15 months after implantation.
PMID- 29344374
TI - Cardioprotection by an anti-MASP-2 antibody in a murine model of myocardial
infarction.
AB - Background: Myocardial ischaemia-reperfusion injury is a major cause of mortality
and morbidity in the developed world. Many approaches have been investigated to
counteract the pathological consequences associated with acute myocardial
infarction (AMI) and cardiac remodelling. It is accepted that inflammation, and
therefore activation of the complement pathway, is a crucial step in the
pathogenesis of this injury, and many attempts have been made to ameliorate the
infarction and consequent dysfunction using anticomplement therapy, with mixed
success. Recently, the lectin complement activation pathway involving the mannose
binding lectin-associated serine protease 2 (MASP-2) has been shown to be an
important mediator of the inflammatory response in ischaemia/reperfusion injury
in the heart. In this study, therefore, we aimed to investigate the feasibility
of using monoclonal antibodies raised against MASP-2 in a murine model of AMI.
Methods: Mice were injected with anti-MASP-2 antibody or control 18 hours prior
to experimental infarction by ligation of the left anterior descending coronary
artery for 30 min followed by 120 min reperfusion. The developed infarct was
measured, and blood was collected for analysis of lectin pathway functional
activity. Results and conclusions: We found that mice treated with anti-MASP-2
antibody had smaller infarcts than those treated with control antibody. We
believe this may represent a valuable step forward in the protection of the
myocardium against ischaemia-reperfusion injury.
PMID- 29344375
TI - Elevated serum levels of cardiovascular biomarkers are associated with
progression of renal cancer.
AB - Objective: Renal cell carcinoma (RCC) is a hypervascular tumour due to high
constitutive production of vascular endothelial growth factor (VEGF), which is
activated by hypoxia-inducible factor (HIF). Elevated levels of cardiovascular
peptides, including brain natriuretic peptide (BNP), have been reported in
patients with cancer, regardless of whether they have overt cardiovascular
disease. Furthermore, it has been demonstrated that hypoxia stimulates BNP
production by an HIF-dependent manner. However, the clinical implications of such
cardiovascular peptides in patients with RCC have not been assessed. Methods: In
patients with clear cell RCC who underwent nephrectomy, we investigated the
relationship between the serum level of BNP or N-terminal pro-BNP (NT-proBNP) and
various clinicopathological characteristics, including serum VEGF and expression
of BNP and HIF-2 alpha in the primary tumour. Results: Elevated preoperative
serum levels of BNP, NT-proBNP and VEGF, as well as increased tumour expression
of HIF-2 alpha, were associated with a worse performance status, local invasion,
distant metastasis and shorter overall survival. HIF-2 alpha expression showed a
positive correlation with the preoperative serum VEGF level, while there was no
relation between the serum levels of BNP/NT-proBNP and VEGF or tumour expression
of HIF-2 alpha. BNP expression was very low in both tumour tissues and normal
kidney tissues. Serum levels of BNP, NT-proBNP and VEGF all decreased
significantly after nephrectomy. Conclusions: Our findings suggested that the
preoperative serum levels of BNP and NT-proBNP are markers of tumour progression,
as well as indicators of subclinical functional and structural myocardial damage
in patients with advanced RCC.
PMID- 29344376
TI - Effectiveness of pharmacist's intervention in the management of cardiovascular
diseases.
AB - The pharmacist may play a relevant role in primary and secondary prevention of
cardiovascular diseases, mainly through patient education and counselling, drug
safety management, medication review, monitoring and reconciliation, detection
and control of specific cardiovascular risk factors (eg, blood pressure, blood
glucose, serum lipids) and clinical outcomes. Systematic reviews of randomised
controlled and observational studies have documented an improved control of
hypertension, dyslipidaemia or diabetes, smoking cessation and reduced
hospitalisation in patients with heart failure, following a pharmacist's
intervention. Limited proof for effectiveness is available for humanistic
(patient satisfaction, adherence and knowledge) and economic outcomes. A
multidisciplinary approach, including medical input plus a pharmacist, specialist
nurse or both, and a greater involvement of community rather than hospital
pharmacists, seems to represent the most efficient and modern healthcare delivery
model. However, further well-designed research is demanded in order to
quantitatively and qualitatively evaluate the impact of pharmacist's
interventions on cardiovascular disease and to identify specific areas of impact
of collaborative practice. Such research should particularly focus on the
demonstration of a sensitivity to community pharmacist's intervention. Since
pharmacy services are easily accessible and widely distributed in the community
setting, a maximum benefit should be expected from interventions provided in this
context.
PMID- 29344377
TI - Major adverse cardiac and cerebrovascular event and patients' quality of life
after endoscopic vein harvesting as compared with open vein harvest (MAQEH): a
pilot study.
AB - Background: This is a prospective, comparative, pilot and follow-up (2-year
postoperatively) study in patients undergoing coronary artery bypass graft
surgery where the long saphenous vein was harvested either by the endoscopic vein
harvest (EVH) technique or open vein harvest (OVH) technique. Quality of life
(QOL) and major adverse cardiac and cerebrovascular events (MACCE) were assessed.
Methods: Alive patients who were initially part of a pilot study when EVH was
introduced in our institution were included (n=48 EVH, n=49 OVH). Patients were
sent a QOL questionnaire (SF12v2; 12-item medical outcomes study short form
health survey version 2.0), and their cardiologist and general practitioner were
contacted to assess MACCE. Results: Median follow-up was 32 and 33 months,
respectively. Three patients died (2 EVH, 1 OVH). Of the remaining 97 patients
who were sent a questionnaire, 76% patients returned the form. More patients from
the EVH group returned the QOL questionnaire (82% vs 71%). Time taken to return
to normal daily activities was much shorter in EVH (median 6 (2-30) weeks)
compared with OVH (median 9 (2-50) weeks) (P<0.05). QOL questionnaire revealed
significant difference in physical score at follow-up: 45.3 (10.2) for EVH group
and 40.7 (11.0) for OVH group (P<0.05). There was no difference in mental scores
(46.9 (10.5) vs 49.2 (9.1), P=0.4). There were no significant differences in
MACCEs including death between the two groups (12.2% vs 13.9%, P=0.5).
Conclusion: EVH patients returned to normal daily activities faster than OVH
patients and experienced better physical QOL even after 2 years postoperatively
with no increase in MACCE during follow-up.
PMID- 29344378
TI - Clinical outcomes and costs of cardiac revascularisation in England and New York
state.
AB - Objectives: Healthcare expenditure per-capita in the USA is higher than in
England. We hypothesised that clinical outcomes after cardiac revascularisation
are better in the USA. We compared costs and outcomes of patients undergoing
coronary artery bypass grafting (CABG) and percutaneous coronary intervention
(PCI) in England and New York State (NYS). Methods: Costs and total mortality
were assessed using the Hospital Episode Statistics for England and the Statewide
Planning and Research Cooperative System for NYS. Outcomes after a first CABG or
PCI were assessed in patients undergoing a first CABG (n=142 969) or PCI (n=431
416). Results: After CABG, crude total mortality in England was 0.72% lower at 30
days and 3.68% lower at 1 year (both P<0.001). After PCI, crude total mortality
was 0.35% lower at 30 days and 3.55% lower at 1 year (both P<0.001). No
differences emerged in total mortality at 30 days after either CABG (England: HR
1.02,95% CI 0.94 to 1.10) or PCI (HR 1.04, 95% CI 0.99 to 1.09) after covariate
adjustment. At 1 year, adjusted total mortality was lower in England after both
CABG (HR 0.74, 95% CI 0.71 to 0.78) and PCI (HR 0.66, 95% CI 0.65 to 0.68). After
adjustment for cost-to-charge ratios and purchasing power parities, costs in NYS
amounted to uplifts of 3.8-fold for CABG and 3.6-fold for PCI. Conclusions: Total
mortality after CABG and PCI was similar at 30 days and lower in England at 1
year. Costs were approximately fourfold higher in NYS.
PMID- 29344379
TI - Changes in contractile protein expression are linked to ventricular stiffness in
infants with pulmonary hypertension or right ventricular hypertrophy due to
congenital heart disease.
AB - Background: The right ventricle (RV) is not designed to sustain high pressure
leading to failure. There are no current medications to help RV contraction, so
further information is required on adaption of the RV to such hypertension.
Methods: The Right Ventricle in Children (RVENCH) study assessed infants with
congenital heart disease undergoing cardiac surgery with hypertensive RV.
Clinical and echocardiographic data were recorded, and samples of RV were taken
from matched infants, analysed for proteomics and compared between pathologies
and with clinical and echocardiographic outcome data. Results: Those with
tetralogy of Fallot (TOF) were significantly more cyanosed than those with
ventricular septal defect (median oxygen saturation 83% vs 98%, P=0.0038), had
significantly stiffer RV (tricuspid E wave/A wave ratio 1.95 vs 0.84, P=0.009)
and had most had restrictive physiology. Gene ontology in TOF, with enrichment
analysis, demonstrated significant increase in proteins of contractile mechanisms
and those of calmodulin, actin binding and others associated with contractility
than inventricular septal defect. Structural proteins were also found to be
higher in association with sarcomeric function: Z-disc, M-Band and thin-filament
proteins. Remaining proteins associated with actin binding, calcium signalling
and myocyte cytoskeletal development. Phosphopeptide enrichment led to higher
levels of calcium signalling proteins in TOF. Conclusion: This is the first
demonstration that those with an RV, which is stiff and hypertensive in TOF, have
a range of altered proteins, often in calcium signalling pathways. Information
about these alterations might guide treatment options both in terms of
individualised therapy or inotropic support for the Right ventricle when
hypertensive due to pulmoanry hypertension or congenital heart disease.
PMID- 29344380
TI - Sex-stratified analysis of national trends and outcomes in isolated tricuspid
valve surgery.
AB - Objective: Female sex is a known risk factor for cardiac surgery, and tricuspid
valve (TV) disease is more common in women. There are few data on sex-stratified
surgical outcomes for isolated TV surgery. An administrative database was used to
compare acute in-hospital outcomes between men and women undergoing isolated TV
surgery. Methods: Patients aged >18 who underwent TV repair or replacement from
2004 to 2013 were identified using the National Inpatient Sample. Patients were
excluded if they had congenital heart disease, endocarditis, or were undergoing
concomitant cardiac surgeries except coronary bypass. Results were weighted to
represent national averages. Sex-stratified analysis was performed using
propensity score matching to compare in-hospital mortality, postoperative
complications and hospital costs. Results: Over 10 years, women represented 58%
of the 5005 TV surgeries performed. With propensity matching, hospital mortality
(7.9% vs 7.7%; P=0.99) and median length of stay (11 vs 11 days; P=0.99) were
similar between men and women. However, median hospital charges were higher for
men ($166 000 vs $155 000; P=0.04). Conclusion: Isolated TV surgery is rare, but
women more commonly undergo the procedure. In-hospital mortality was similar
between men and women after propensity matching, but remains markedly high for
both men and women in comparison to that reported for left-sided isolated valve
surgery.
PMID- 29344381
TI - Impact of nutritional indices on mortality in patients with heart failure.
AB - Background: Malnutrition is a common condition that is associated with adverse
prognosis in patients with heart failure (HF). The Prognostic Nutritional Index
(PNI), Geriatric Nutritional Risk Index (GNRI) and controlling nutritional status
(CONUT) have all been used as objective indices for evaluating nutritional
status. We aimed to clarify the relationship between these nutritional indices
and the parameters of inflammatory markers, cardiac function and exercise
capacity, as well as to compare the ability of these indexes for predicting
mortality. Methods: We evaluated PNI, GNRI and CONUT in consecutive 1307 patients
with HF. Results: First, there were significant correlations between nutritional
indices and the following: C reactive protein; tumour necrosis factor-alpha;
adiponectin; B-type natriuretic peptide; troponin I; inferior vena cava diameter
and peak VO2 (P<0.05, respectively). Second, in the Kaplan-Meier analysis (follow
up 1146 days), all-cause mortality progressively increased from normal to mild,
moderate and severe disturbance groups in the indices (log-rank, P<0.01,
respectively). In the Cox proportional hazard analysis, each index was an
independent predictor of all-cause mortality in patients with HF (P<0.001,
respectively). Third, receiver operating curve demonstrated that the areas under
the curve of PNI and GNRI were larger than that of CONUT score (P<0.05,
respectively). Conclusion: Patients with HF being malnourished had higher
mortality accompanied by higher levels of C reactive protein, tumour necrosis
factor-alpha, adiponectin, B-type natriuretic peptide, troponin I, right-sided
volume overload and impaired exercise capacity, rather than left ventricular
systolic function. Additionally, PNI and GNRI were superior to CONUT score in
predicting mortality in patients with HF.
PMID- 29344382
TI - Advanced therapies for the management of adults with pulmonary arterial
hypertension due to congenital heart disease: a systematic review.
AB - Pulmonary arterial hypertension (PAH) secondary to congenital heart disease (CHD)
is the third most common cause of PAH, and it is becoming increasingly common as
improvements in the management of CHD have led to increased life expectancy for
these patients. The medical management of PAH due to CHD (PAH-CHD) is largely the
same as what has been used for the treatment of idiopathic PAH, though the body
of literature supporting this management decision is very small. There are
currently few studies available which specifically focus on the treatment of PAH
CHD. The purpose of this literature review is to compare the results of those
studies that assessed the response to medical therapy among adults with PAH-CHD;
studies were excluded if they focused on paediatric patients, did not include an
assessment of 6 min walking distance or specifically assessed combination
therapies. This review found that riociguat, bosentan, epoprostenol and
sildenafil were all capable of improving functional capacity and haemodynamic
parameters in patients with PAH-CHD, but whether this corresponds to an increase
in mortality remains to be seen. Limitations of this review include the small
sample size and variable duration of the included studies, which makes drawing
direct comparisons between studies and the study drugs difficult. The lack of
large, randomised double-blind clinical trials comparing different drugs head to
head highlights an area that is ripe for ongoing medical research, the results of
which may help shape future treatment algorithms tailored specifically for adults
with PAH-CHD.
PMID- 29344383
TI - Prognosis of patients with secondary mitral regurgitation and reduced ejection
fraction.
AB - Objective: The impact of the severity of secondary mitral regurgitation (MR) on
the risk of death and heart failure (HF) hospitalisations in patients with
reduced left ventricular (LV) systolic function is poorly defined. The study
sought to identify the incremental risk of secondary MR in patients with reduced
LV systolic function. Methods: We studied 615 consecutive patients with LV
ejection fraction <=35% by transthoracic echocardiography at a single medical
centre. Patients were divided into three groups of no MR, mild, or moderate to
severe MR. The median follow-up was 2.9 years. The primary endpoint was a
composite of death or HF hospitalisations. Results: Compared with patients with
no MR, the risk of death or HF hospitalisations was higher for mild MR (HR 1.7,
P=0.003) and moderate to severe MR (HR 2.7, P<0.001). The risk was also higher
for the component endpoints of HF hospitalisations (mild MR: HR 2.3, P=0.001;
moderate to severe MR: HR 3.5, P<0.001) and death (mild MR: HR 1.6, P=0.033;
moderate to severe MR: HR 2.6, P<0.001). After adjustment for other covariates,
MR was no longer significantly associated with death or HF hospitalisations, or
death alone, but remained significantly associated with HF hospitalisations (mild
MR: HR 1.7, P=0.028; moderate to severe MR: HR 2.2, P=0.002). Conclusions: In
patients with reduced LV systolic function, secondary MR is associated with an
increased risk of HF hospitalisations but not death.
PMID- 29344384
TI - Blood pressure target achievement and antihypertensive medication use in women
and men after first-ever myocardial infarction: the Tromso Study 1994-2016.
AB - Background: Recurrent cardiovascular events after myocardial infarction (MI) are
frequent, and gender differences in blood pressure treatment have been reported.
Despite increased focus on secondary prevention, recent reports indicate that
treatment targets are not achieved. There is a need for gender-specific analyses
of post-MI blood pressure treatment target achievement and antihypertensive
medication adherence. Design: We investigated the change in systolic and
diastolic blood pressure and antihypertensive drug use after first-ever MI over
two time periods in a Norwegian population-based study. Methods: We followed 10
089 participants (55% women) attending the Tromso Study in 1994-1995 (MI-cohort
I) and 8412 participants (55% women) attending the Tromso Study 2007-2008 (MI
cohort II) for first-ever MI up to their participation in 2007-2008 and 2015
2016, respectively. We used linear regression models to investigate sex and age
differences in change in blood pressure. Results: A total of 396 participants in
MI-cohort I and 131 participants in MI-cohort II had a first-ever MI in the
observation periods. In MI-cohort I, 35% of the women and 52% of the men achieved
the treatment targets of blood pressure <140/90 mm Hg (130/80 mm Hg if diabetic),
while the proportions for MI-cohort II were 50% and 54% for women and men,
respectively. Antihypertensive use was reported in 88% of women and 87% of men in
MI-cohort I, and 76% of women and 81% of men in MI-cohort II. Conclusions: We
found an overall low achievement of the treatment target. The findings call for
better strategies for secondary prevention for both women and men.
PMID- 29344385
TI - Improving attendance to genetic counselling services for gynaecological oncology
patients.
AB - Background: Gynaecological cancers may be the sentinel malignancy in women who
carry a mutation in BRCA1 or 2, a mis-match repair gene causing Lynch Syndrome or
other genes. Despite published guidelines for referral to a genetics service, a
substantial number of women do not attend for the recommended genetic assessment.
The study aims to determine the outcomes of systematic follow-up of patients
diagnosed with ovarian or endometrial cancer from Gynaecologic-oncology
multidisciplinary meetings who were deemed appropriate for genetics assessment.
Methods: Women newly diagnosed with gynaecological cancer at the Royal Hospital
for Women between 2010 and 2014 (cohort1) and 2015-2016 (cohort 2) who were
identified as suitable for genetics assessment were checked against the New South
Wales/Australian Capital Territory genetic database. The doctors of non-attenders
were contacted regarding suitability for re-referral, and patients who were still
suitable for genetics assessment were contacted by mail. Attendance was again
checked against the genetics database. Results: Among 462 patients in cohort 1,
flagged for genetic assessment, 167 had not consulted a genetic service at
initial audit conducted in 2014. 86 (18.6%) women whose referral was pending
clarification of family history and/or immunohistochemistry did not require
further genetic assessment. Letters were sent to 40 women. 7 women (1.5%)
attended hereditary cancer clinic in the following 6 months.The audit conducted
in 2016 identified 148 patients (cohort 2) appropriate for genetic assessment at
diagnosis. 66 (44.6%) had been seen by a genetics service, 51 (34.5%) whose
referral was pending additional information did not require further genetic
assessment. Letters were sent to 15 women, of whom 9 (6.1%) attended genetics
within 6 months. Conclusions: To improve the effectiveness of guidelines for the
genetic referral of women newly diagnosed with ovarian cancer, clinicians need to
obtain a thorough family history at diagnosis; arrange for reflex MMR IHC
according to guidelines; offer BRCA or panel testing to all women with non
mucinous ovarian cancer prior to discharge and systematically follow up all women
referred to genetics at the post-op visit.
PMID- 29344386
TI - Current and future therapies for SLE: obstacles and recommendations for the
development of novel treatments.
AB - SLE is a serious, debilitating autoimmune disease that affects various organs and
body systems. Of all the heterogeneous autoimmune diseases, SLE is perhaps the
most heterogeneous. Patients with SLE, who are primarily female, have diverse
disease manifestations and severity. SLE is characterised by substantial
concentrations of autoantibodies against nuclear antigens, which are thought to
be caused by immune cell dysregulation. Until recently, several immunosuppressant
agents were used to treat this disease. Efforts to develop drugs against targets
potentially involved in disease mechanisms have resulted in the identification
and use of BAFF (B-cell activating factor)/APRIL (a proliferation-inducing
ligand) inhibitors to treat SLE. Drugs in late-stage development that focus on
pathways that are dysregulated in SLE include those that target the interferon
pathway, T-cell signalling and B-cell signalling. New therapeutic agents are
still necessary because of the unmet medical needs associated with this disease,
including insufficient disease control, poor health-related quality of life,
comorbidities, toxicity of the majority of therapies and diminished survival.
Despite the substantial long-term investment of research, clinical activity and
resources for identifying new treatments for this disease, only one new therapy,
the biological belimumab, has been approved in the past 50 years. Efforts to
develop drugs to address these needs are challenged by problems associated with
disease heterogeneity, variable disease mechanisms and trial design. This review
provides an overview of current and future treatments, discusses challenges in
the SLE drug development process and offers recommendations for overcoming these
challenges.
PMID- 29344387
TI - Repository corticotropin injection in patients with persistently active SLE
requiring corticosteroids: post hoc analysis of results from a two-part, 52-week
pilot study.
AB - Objective: Post hoc analyses evaluated the effectiveness and safety of repository
corticotropin injection (RCI) in patients with persistently active SLE over 52
weeks. Methods: Patients were initially randomised to 40 U daily or 80 U every
other day RCI (n=26) or placebo (n=12) for the 8-week double-blind period.
Completers entered the open-label extension (OLE; n=33) receiving 16, 40 or 80 U
RCI 1-3 times/week and were followed through week 52. Outcomes included
proportion of responders based on a novel index (resolution of joint or skin
activity using hybrid Systemic Lupus Erythematosus Disease Activity Index
(hSLEDAI) without any worsening British Isles Lupus Assessment Group (BILAG)
scores in other organ systems) or revised novel index (using SLE Responder Index
(SRI) definition of BILAG worsening (1A or 2B)), proportion of responders by SRI
and changes in total hSLEDAI and BILAG scores. Adverse events and laboratory
values were assessed. Results: At week 52, 12.0% (3/25) RCI/RCI patients and
36.4% (4/11) placebo/RCI patients were responders using the novel index. The
revised novel responder index demonstrated response rates of 48.0% (12/25) and
54.5% (6/11) in the RCI/RCI and placebo/RCI groups, respectively. Proportions of
SRI responders were 40.0% (10/25) and 54.5% (6/11). In the RCI/RCI group, total
hSLEDAI and BILAG scores declined from 10.0 and 15.7 at week 0 to 3.5 and 4.6 at
week 52, respectively. Reductions in the placebo/RCI group on switching were
observed (mean hSLEDAI: 9.1-3.3; BILAG: 13.5-2.6). Other disease activity
endpoints also improved in both groups. No new safety signals were observed
during the OLE. Conclusions: RCI demonstrated durable effectiveness in patients
with persistently active SLE despite moderate-dose corticosteroid therapy.
Switching from placebo resulted in reduced disease activity during the OLE. These
data provide the foundation for evaluation of RCI in a robustly powered study.
PMID- 29344388
TI - Gender-based violence and the role of healthcare professionals.
PMID- 29344389
TI - Family members' satisfaction with care and decision-making in intensive care
units and post-stay follow-up needs-a cross-sectional survey study.
AB - Aim: The aim of this study was to explore family members' satisfaction with care
and decision-making during the intensive care units stay and their follow-up
needs after the patient's discharge or death. Design: A cross-sectional survey
study was conducted. Methods: Family members of patients recently treated in an
ICU were participating. The questionnaire contented of background variables, the
instrument Family Satisfaction in ICU (FS-ICU 24) and questions about follow-up
needs. Descriptive and non-parametric statistics and a multiple linear regression
were used in the analysis. Results: A total of 123 (47%) relatives returned the
questionnaire. Satisfaction with care was higher scored than satisfaction with
decision-making. Follow- up needs after the ICU stay was reported by 19 (17%) of
the participants. Gender and length of the ICU stay were shown as factors
identified to predict follow-up needs.
PMID- 29344390
TI - Job-related stress in psychiatric assistant nurses.
AB - Aim: We aimed to clarify how stress among psychiatric assistant nurses (PANs)
differed from Registered Nurses (PRNs). Design: Cross-sectional survey study was
conducted with PRNs and PANs working in six psychiatric hospitals in Japan.
Methods: The Psychiatric Nurse Job Stressor Scale (PNJSS) and the job stressor
and stress reaction subscales of the Brief Job Stress Questionnaire measured
stress in 68 PANs and 140 PRNs. The results were statistically analysed. Results:
Psychiatric assistant nurses had significantly higher scores than PRNs on the job
stressor subscales in psychiatric nursing ability, interpersonal relations and in
the stress reaction subscales of irritability and somatic symptoms. "Psychiatric
nursing ability," "Communication" and "Use of techniques" were associated with
almost all stress reactions in PANs than in PRNs.
PMID- 29344391
TI - Pilot study: Assessing the effect of continual position monitoring technology on
compliance with patient turning protocols.
AB - Aim: The study aim was to evaluate if continual patient position monitoring,
taking into account self-turns and clinician-assisted turns, would increase the
percentage of time a patient's position changed at least every 2 hr. Background:
While patient turning has clinical benefits, current models to help staff
remember to turn patients, such as "turn clocks" and timers, have not resulted in
high compliance with turning protocols. In addition, reminders are based on
arbitrary 2-hr windows (such as turning on "even" hours) rather than on
individual patient activity, including self-turns. Design: This is a first
inpatient, non-randomized, pre-/postintervention study. Methods: Data collection
occurred from May 2013-February 2014 on a 39-bed medical unit in a community
hospital. Baseline patient turning data were recorded by a sensor; however, the
patient data were not displayed at the nurses' station to establish compliance
with the hospital's turning protocol. Postintervention, patient position
information was wirelessly displayed on nurses' station computer monitors in real
time. A Student t test was used to compare baseline to postintervention "mean
time in compliance." Results: Data from 138 patients (N = 7,854 hr of monitoring)
were collected. The baseline phase yielded 4,322 hr of position monitoring data
and the postintervention phase yielded 3,532 hr of data. Statistically
significant improvement was demonstrated in the percentage of time a patient's
position changed at least every 2 hr from baseline to postintervention.
PMID- 29344392
TI - Evaluating the parent-adolescent communication toolkit: Usability and preliminary
content effectiveness of an online intervention.
AB - Aim: This study aimed to assess the Parent-Adolescent Communication Toolkit, an
online intervention designed to help improve parent communication with their
adolescents. Participant preferences for two module delivery systems (sequential
and unrestricted module access) were identified. Design: Usability assessment of
the PACT intervention was completed using pre-test and posttest comparisons.
Usability data, including participant completion and satisfaction ratings were
examined. Methods: Parents (N = 18) of adolescents were randomized to a
sequential or unrestricted chapter access group. Parent participants completed
pre-test measures, the PACT intervention and posttest measures. Participants
provided feedback for the intervention to improve modules and provided usability
ratings. Adolescent pre- and posttest ratings were evaluated. Results: Usability
ratings were high and parent feedback was positive. The sequential module access
groups rated the intervention content higher and completed more content than the
unrestricted chapter access group, indicating support for the sequential access
design. Parent mean posttest communication scores were significantly higher (p <
.05) than pre-test scores. No significant differences were detected for
adolescent participants. Findings suggest that the Parent-Adolescent
Communication Toolkit has potential to improve parent-adolescent communication
but further effectiveness assessment is required.
PMID- 29344393
TI - Effect of standardized nursing language continuing education programme on nurses'
documentation of care at University College Hospital, Ibadan.
AB - Aim: The study assessed the documentation of nursing care before, during and
after the Standardized Nursing Language Continuing Education Programme (SNLCEP).
It evaluates the differences in documentation of nursing care in different
nursing specialty areas and assessed the influence of work experience on the
quality of documentation of nursing care with a view to provide information on
documentation of nursing care. The instrument used was an adapted scoring guide
for nursing diagnosis, nursing intervention and nursing outcome (Q-DIO). Design:
Retrospective record reviews design was used. Methods: A total of 270 nursing
process booklets formed the sample size. From each ward, 90 booklets were
selected in this order: 30 booklets before the SNLCEP, 30 booklets during SNLCEP
and 30 booklets after SNLCEP. Results: Overall, the study concluded that the
SNLCEP had a significant effect on the quality of documentation of nursing care
using Standardized Nursing Languages.
PMID- 29344394
TI - Patient participation, a prerequisite for care: A grounded theory study of
healthcare professionals' perceptions of what participation means in a paediatric
care context.
AB - Aims: To explore healthcare professionals' perceptions of what patient
participation means in a paediatric care context . Design: A qualitative
explorative design with grounded theory. Methods: Fifteen healthcare
professionals who worked in paediatric care settings were either interviewed or
asked open-ended questions in a survey, during December 2015-May 2016. Grounded
theory was used as a method. Results: The study results provide a theoretical
conceptualization of what patient participation meant for healthcare
professionals in paediatric care and how participation was enabled. The core
category "participation a prerequisite for care" emerged as the main finding
explaining the concept as ethical, practical and integrated in the care givers
way of working. However, the concept was implicit in the organization. Four
additional categories illustrated the healthcare professionals' different
strategies used to enhance patient participation; "meeting each child where the
child is," "building a relationship with the child," "showing respect for each
individual child" and "making the most of the moment."
PMID- 29344395
TI - Nurse anaesthetist students' experiences of patient dignity in perioperative
practice-a hermeneutic study.
AB - Aim: The aim of the study was to describe how nurse anaesthetist students
experienced patient dignity in perioperative practice. Design: A hermeneutical
design and the critical incident technique were used to obtain experiences from
practice. Method: In the Autumn of 2015, after participating in a mandatory
lecture on ethics, 23 nurse anaesthetist students reported their experiences and
interpretation concerning violation and preservation of patients' dignity in the
operating theatre. The text, which was a compilation of descriptions of 35
incidents, was analysed by using hermeneutical text interpretation. Findings: The
text revealed three main themes preserving patients' dignity: allocating time to
the patient, inviting the patient to participate and shielding the patient's
body. Furthermore, three main themes of dignity violation were identified:
alienation, backbiting and violation of intimate sphere. Conclusion: Discussion
and reflection based on the personal experience of the students during their
practice are ways to strengthen ethical awareness and promote an ethical and
dignified caring culture.
PMID- 29344396
TI - Adversity of prolonged extreme cold exposure among adult clients diagnosed with
coronary artery diseases: a primer for recommending community health nursing
intervention.
AB - Aim: This research study explored the lived experiences of adults diagnosed with
Coronary Artery Disease (CAD) when exposed to a prolonged period of extreme cold.
Design: This research study utilized descriptive qualitative research design.
Methods: Face-to-face interview sessions with audio recording were conducted.
There were 30 informants who participated in the study. Descriptive phenomenology
with Colaizzi's method of data analysis was used. Results: Results revealed three
themes, namely: (i) elucidating cold exposure; (ii) challenges of cold exposure;
and (iii) translating adverse exposure to self-management. The results further
revealed the significance of nursing health care especially to health promotion,
disease prevention and health restoration especially in community setting.
Conclusion: In conclusion, manifestations of CAD are triggered when exposed to a
prolonged period of extremely low environmental temperature.
PMID- 29344397
TI - A cross-sectional study of stress and its sources among health professional
students at Makerere University, Uganda.
AB - Aim: To assess prevalence of stress and its sources among undergraduate health
professional students at Makerere University. Design: This was a descriptive
cross-sectional study using quantitative methods of data collection. Methods: The
study was conducted among 258 undergraduate health professional students
(Medical, Dental and, Nursing students) at Makerere University. From each
programme, students were recruited proportionately, while being selected
conveniently from each year of study. Stress was measured using the General
Health Questionnaire 12 and stressors assessed using a questionnaire developed
from literature. After obtaining ethics approval, data were collected from
consenting students. Data collected were analysed using SPSS statistical program.
Results: The prevalence of stress was found to be 57.4% and stressors of academic
and psychosocial origin were most frequently reported. The top stressors
included; academic curriculum (38%), dissatisfaction with class lectures (30.9%),
long distance walk (29.5%), lack of time for recreation (28.9%), performance in
examination (28.3%), lack of special guidance from faculty (26.7%) and high
parental expectations (26.7%).
PMID- 29344398
TI - Exploring nurse managers' perception of using the RAFAELA system as a management
tool in a Norwegian hospital setting.
AB - Aim: The aim of the study, being part of a Norwegian evaluation project of the
RAFAELA system, was to explore nurse managers' perception of the RAFAELA system
as a management tool in a Norwegian hospital setting. Design: We applied an
explorative qualitative design using focus group interviews. Methods: Two focus
group interviews were performed with 12 nurses in different management positions
during autumn 2013. The principles of qualitative content analysis were used for
analysing data. Results: Three themes emerged. The informants experienced the
RAFAELA system to be a basis for a precise and common langue. Furthermore, the
informants considered it to be a system defining quality standards of nursing
care. Finally, the RAFAELA system provided daily documentation of nursing
intensity and thus was considered an important management tool for balancing
patient needs with appropriate staff.
PMID- 29344399
TI - Contested discourses and culture sensitivity: Norwegian nursing students'
experience of clinical placement in Nicaragua.
AB - Aim: The purpose of this study was to gain understanding of Norwegian students'
practical experience of "culture sensitivity." Design: Using focus-group
interviews and individual written assignments, we draw on a Foucauldian-inspired
approach to analyse nursing students' narratives about their clinical placement
in Nicaragua. Method: Seven third-year bachelor nursing students enrolled in a
clinical placement programme on the Caribbean coast in Nicaragua and participated
in focus-group interviews. Interviews were conducted prior to their departure to
Nicaragua and after their return to Norway. Other sources of data included
learning objectives for clinical placement, written individual assignments with
students' reflections about their experiences and achievement of learning
objectives. Results: Students expressed gradually increased awareness about the
nursing discourses and power relations shaping clinical encounters throughout
their learning trajectory in clinical placement. They became more aware of the
politics of nursing practices through their experiences of clashes between
different nursing discourses.
PMID- 29344400
TI - The nursing legacy of the Korea Sisters.
AB - Aim: During the Korean War (1950-1953), the Norwegian government sent a Mobile
Army Surgical Hospital (MASH) to support the efforts of the United Nations (UN)
Army. During the war, 111 Norwegian nurses served in seven contingents, each 6
month, at the Norwegian Field Hospital in Korea. The nurses were nicknamed "The
Korea Sisters". The aim of this study is to explore the impact and influence of
their wartime nursing on Norwegian post-Korean-War nursing. Design: Qualitative.
Methods: The study uses several historical research approaches. Interview,
archival search, search in nursing periodicals, contemporary magazines and
nursing text books. Result: The nursing legacy of The Korea Sisters can be found
in changes in general nursing, uniform education of theatre nurses, uniform
education of anaesthetist nurses and in humanitarian work.
PMID- 29344401
TI - Protocol for Moving On: a randomized controlled trial to increase outcome
expectations and exercise among breast cancer survivors.
AB - Aim: The aim of this study was to test the feasibility and fidelity of an
intervention, Moving On, aimed to increase outcome expectations OEs (i.e. what
one expects to obtain or avoid as a result of a behaviour) and exercise among
breast cancer survivors. Design: Randomized controlled trial. Methods:
Intervention arm participants will be given a theory-guided booklet that was co
created by the research team and three physically active breast cancer survivors
who exercise to manage late and long-term treatment effects. Attention control
arm participants will be given a similar booklet focused on diet. Participants
will have 1 week to complete reading, writing and reflecting activities in the
booklets. Study outcomes will be measured through online surveys; exercise will
also be measured objectively with a Fitbit(r). Four weeks postintervention,
participants' thoughts about the usefulness, strengths and weakness of the
intervention booklet will be assessed. OEs and exercise will be measured at
baseline, 4-, 8- and 12-week postintervention.
PMID- 29344402
TI - Young Asian men with diabetes have the highest risk for acute coronary events:
retrospective cohort analyses.
AB - Objective: To understand the ethnic differences in coronary heart disease risk
among inpatients with diabetes following acute coronary syndrome. Design: Single
centre retrospective cohort-analysis of patients with type II diabetes over a six
year period receiving standard care. Setting: Birmingham, UK. Participants: One
thousand and one hundred and five patients with type II diabetes from a multi
ethnic background. Main outcome measures: Odds ratios of coronary heart disease
events among three ethnic groups. Results: The prevalence of coronary heart
disease events was 20.7% in Asian, 13.2% in Caucasian and 7.7% in Afro-Caribbean
patients. Asian patients were younger at diagnosis of diabetes (-5.1 years p <
0.001 versus Afro-Caribbeans and -7.1 years p < 0.001 versus Caucasians). The
mean number of events was highest amongst Asian (1.2) compared to Caucasian (1.1)
and Afro-Caribbean (1.0) patients (p = 0.04). The mean age at first event was
61.3 years for Asians, 62.5 years and 65.8 for Afro-Caribbeans and Caucasians,
respectively (analysis of variance F[2,131] = 2.36 p = 0.09). Un-adjusted odds
ratios for at least one coronary heart disease event were highest among Asian men
(OR 5.04; 95% CI 2.31-11.01; p < 0.0001) with Afro-Caribbean women as baseline
(OR 1.0). The odds ratios remain largely unchanged (1.0 Afro-Caribbeans
[baseline], 1.27 [p = 0.56] Caucasians and 3.2 [p = 0.001] for Asians) when
corrected for age, gender, duration of diabetes, insulin dependency, mean low
density lipoprotein-cholesterol, triglycerides and high-density lipoprotein
cholesterol, mean glycated haemoglobin, mean systolic and diastolic blood
pressure (logistic regression; ROC: 79% AUC). Afro-Caribbean patients had the
highest mean high-density lipoprotein-cholesterol (1.6 mmol/L) and the lowest
risk for coronary heart disease events. Conclusions: Asian patients were younger
at their first event and diagnosed earlier with diabetes. Asian men had the
highest risk of coronary heart disease event which correlated with the lowest
levels of high-density lipoprotein-cholesterol.
PMID- 29344403
TI - Maternal morbidity and mortality associated with retroperitoneal haematomas in
pregnancy.
AB - Retroperitoneal haematomas in obstetrics are uncommon. The causes and
pathogenesis of retroperitoneal haematomas lack clarity and the aim of this
review is to recognise retroperitoneal haematomas as a separate entity from
commonly seen vaginal and pelvic haematomas. It is time to raise awareness among
obstetricians to recognise retroperitoneal haematomas as an important cause of
maternal morbidity and mortality which requires high clinical suspicion and
multidisciplinary input. As retroperitoneal haematomas are rare but can cause
serious threat to maternal wellbeing, resources should be directed towards their
management. Existing guidelines of maternal collapse and morbidity during
pregnancy and puerperium need to include retroperitoneal haematomas as one of the
important causes of maternal shock or morbidity. New learning pathways should be
opted for to increase awareness of retroperitoneal haematomas among obstetricians
enabling them to reflect on their implications while managing retroperitoneal
haematomas. Management of retroperitoneal haematomas is complex and continues to
improve with advancements in the investigative strategies, treatment options and
multidisciplinary involvement.
PMID- 29344404
TI - Unleashing the tiger - iatrogenic autoimmunity from cancer immunotherapy drugs.
AB - Immune checkpoint inhibitors can lead to the development of organ and non-organ
specific immune related adverse events.
PMID- 29344406
TI - Research protocol: investigating the feasibility of a group self-management
intervention for stroke (the GUSTO study).
AB - Background: Life after stroke can be an ongoing struggle with over half of all
survivors reporting unmet emotional and social needs. In the United Kingdom's
(UK) national clinical guidelines for stroke, self-management is suggested as one
approach which can support long-term needs. In the UK NHS, self-management
interventions are delivered in various ways. Regardless of the delivery
mechanism, a tailored approach and ways to integrate peer support are advocated.
Group delivery offers a platform for peer support and has the potential to remain
individualised. However, before the efficacy of a group self-management
intervention can be tested, the feasibility must be explored. This research
investigates the feasibility of a GroUp Self-management intervention for sTrOke
(GUSTO). Methods: A randomised waitlist control design will be used to
investigate the feasibility of a group self-management intervention adapted from
an existing one-to-one intervention called Bridges. A mixed methods approach will
be used. Qualitative work will capture participant experience, while quantitative
work will allow preliminary comparison between the intervention and waitlist
groups (between subjects) and pre-post intervention measures (within subjects).
Interviews will be conducted with stroke survivors and focus groups with family
and friends to assess acceptability of the intervention. Discussion: There is a
growing interest in group-based self-management interventions for stroke as a
method of supporting stroke survivors' ongoing unmet needs. This is an area with
limited research to date. This study will inform design of a fully powered trial
which would assess the efficacy of a group self-management intervention following
stroke. Trial registration: ISRCTN19867168.
PMID- 29344405
TI - Lee Silverman Voice Treatment versus standard speech and language therapy versus
control in Parkinson's disease: a pilot randomised controlled trial (PD COMM
pilot).
AB - Background: Speech-related problems are common in Parkinson's disease (PD), but
there is little evidence for the effectiveness of standard speech and language
therapy (SLT) or Lee Silverman Voice Treatment (LSVT LOUD(r)). Methods: The PD
COMM pilot was a three-arm, assessor-blinded, randomised controlled trial (RCT)
of LSVT LOUD(r), SLT and no intervention (1:1:1 ratio) to assess the feasibility
and to inform the design of a full-scale RCT. Non-demented patients with
idiopathic PD and speech problems and no SLT for speech problems in the past 2
years were eligible. LSVT LOUD(r) is a standardised regime (16 sessions over 4
weeks). SLT comprised individualised content per local practice (typically weekly
sessions for 6-8 weeks). Outcomes included recruitment and retention, treatment
adherence, and data completeness. Outcome data collected at baseline, 3, 6, and
12 months included patient-reported voice and quality of life measures, resource
use, and assessor-rated speech recordings. Results: Eighty-nine patients were
randomised with 90% in the therapy groups and 100% in the control group
completing the trial. The response rate for Voice Handicap Index (VHI) in each
arm was >= 90% at all time-points. VHI was highly correlated with the other
speech-related outcome measures. There was a trend to improvement in VHI with
LSVT LOUD(r) (difference at 3 months compared with control: - 12.5 points; 95% CI
- 26.2, 1.2) and SLT (difference at 3 months compared with control: - 9.8 points;
95% CI - 23.2, 3.7) which needs to be confirmed in an adequately powered trial.
Conclusion: Randomisation to a three-arm trial of speech therapy including a no
intervention control is feasible and acceptable. Compliance with both
interventions was good. VHI and other patient-reported outcomes were relevant
measures and provided data to inform the sample size for a substantive trial.
Trial registration: International Standard Randomised Controlled Trial Number
Register: ISRCTN75223808. registered 22 March 2012.
PMID- 29344407
TI - TPF induction chemotherapy increases PD-L1 expression in tumour cells and immune
cells in head and neck squamous cell carcinoma.
AB - Background: Antiprogrammed cell death-1/programmed cell death-ligand 1 (PD-1/PD
L1) therapies have demonstrated promising activity in advanced head and neck
squamous cell carcinoma (HNSCC), with overall response rates of approximately 20%
in unselected populations and survival benefit. Whether induction docetaxel,
platinum and fluorouracil (TPF) modifies PD-L1 expression or tumour immune
infiltrates is unknown. Patients and methods: Patients with locally advanced
HNSCC treated at Gustave Roussy (Villejuif, France) between 2006 and 2013 by
induction TPF followed by surgery were retrospectively considered. Patients with
paired samples (pre-TPF and post-TPF) were kept for further analysis. PD-L1
expression was quantified by immunohistochemistry according to a validated
protocol. The objective of the study was to compare PD-L1 expression on tumour
cells (TC) and immune cells (IC) (positivity threshold of >=5%) before and after
TPF. CD8+ and Foxp3+ lymphocytes densities before and after TPF were also
quantified. Results: Out of 313 patients receiving induction TPF, 86 underwent
surgery; paired samples were available for 21 of them. Baseline PD-L1 expression
was >=5% in two and five samples for TC and IC, respectively. A significant
increase of PD-L1 expression was observed after TPF, with 15 samples (71%)
presenting a positive staining in IC after induction chemotherapy (P=0.003;
Wilcoxon rank-sum test) and eight samples (38%) in TC (P=0.005; Wilcoxon rank-sum
test). Tumour-infiltrating CD8+ mean densities also significantly increased post
TPF (P=0.01). There was no significant difference in Foxp3+ expression, CD8/Foxp3
ratio or correlation with outcome. Conclusion: TPF induction chemotherapy in
advanced HNSCC increases PD-L1 positivity on tumour-infiltrating ICs, as well as
CD8+ lymphocytes density. These results warrant independent validation on larger
datasets and might help therapeutic strategy in advanced HNSCC.
PMID- 29344408
TI - Differential research impact in cancer practice guidelines' evidence base:
lessons from ESMO, NICE and SIGN.
AB - Background: This is an appraisal of the impact of cited research evidence
underpinning the development of cancer clinical practice guidelines (CPGs) by the
professional bodies of the European Society for Medical Oncology (ESMO), the
National Institute for Health and Care Excellence (NICE) and the Scottish
Intercollegiate Guidelines Network (SIGN). Methods: A total of 101 CPGs were
identified from ESMO, NICE and SIGN websites across 13 cancer sites. Their 9486
cited references were downloaded from the Web of Science Clarivate Group
database, analysed on Excel (2016) using Visual Basic Application macros and
imported onto SPSS (V.24.0) for statistical tests. Results: ESMO CPGs mostly
cited research from Western Europe, while the NICE and SIGN ones from the UK,
Canada, Australia and Scandinavian countries. The ESMO CPGs cited more recent and
basic research (eg, drugs treatment), in comparison with NICE and SIGN CPGs where
older and more clinical research (eg, surgery) papers were referenced. This
chronological difference in the evidence base is also in line with that ESMO has
a shorter gap between the publication of the research and its citation on the
CPGs. It was demonstrated that ESMO CPGs report more chemotherapy research, while
the NICE and SIGN CPGs report more surgery, with the results being statistically
significant. Conclusions: We showed that ESMO, NICE and SIGN differ in their
evidence base of CPGs. Healthcare professionals should be aware of this
heterogeneity in effective decision-making of tailored treatments to patients,
irrespective of geographic location across Europe.
PMID- 29344409
TI - Immunotherapy in lung cancer.
PMID- 29344410
TI - Traditional Chinese Medicine and Aging Intervention.
PMID- 29344411
TI - Emerging Roles of Ganoderma Lucidum in Anti-Aging.
AB - Ganoderma lucidum is a white-rot fungus that has been viewed as a traditional
Chinese tonic for promoting health and longevity. It has been revealed that
several extractions from Ganoderma lucidum, such as Ethanol extract, aqueous
extract, mycelia extract, water soluble extract of the culture medium of
Ganoderma lucidum mycelia, Ganodermasides A, B, C, D, and some bioactive
components of Ganoderma lucidum, including Reishi Polysaccharide Fraction 3,
Ganoderma lucidum polysaccharides I, II, III, IV, Ganoderma lucidum peptide,
Ganoderma polysaccharide peptide, total G. lucidum triterpenes and Ganoderic acid
C1 could exert lifespan elongation or related activities. Although the use of
Ganoderma lucidum as an elixir has been around for thousands of years, studies
revealing its effect of lifespan extension are only the tip of the iceberg.
Besides which, the kinds of extractions or components being comfrimed to be anti
aging are too few compared with the large amounts of Ganoderma lucidum
extractions or constituients being discovered. This review aims to lay the ground
for fully elucidating the potential mechanisms of Ganoderma lucidum underlying
anti-aging effect and its clinical application.
PMID- 29344412
TI - Ginseng: An Nonnegligible Natural Remedy for Healthy Aging.
AB - Aging is an irreversible physiological process that affects all humans. Numerous
theories have been proposed to regarding the process from a Western medicine
perspective; however, ancient Chinese medicine practices and theories have
increasingly gained attention, particularly ginseng, a grass that has been
studied for the anti-aging properties of its active constituents. This review
seeks to analyze current data on ginseng and its anti-aging properties. The plant
species, characteristics, and active ingredients will be introduced. The main
part of this review is focused on ginseng and its active components with regards
to their effects on prolonging lifespan, the regulation of multiple organ systems
including cardiovascular, nervous, immune, and skin, as well as the anti-oxidant
and anti-inflammatory properties. The molecular mechanisms of these properties
elucidated via various studies are summarized as further evidence of the anti
aging effects of ginseng.
PMID- 29344413
TI - Therapeutic Potential and Cellular Mechanisms of Panax Notoginseng on Prevention
of Aging and Cell Senescence-Associated Diseases.
AB - Owing to a dramatic increase in average life expectancy, most countries in the
world are rapidly entering an aging society. Therefore, extending health span
with pharmacological agents targeting aging-related pathological changes, are now
in the spotlight of gerosciences. Panax notoginseng (Burk.) F. H. Chen, a species
of the genus Panax, has been called the "Miracle Root for the Preservation of
Life," and has long been used as a Chinese herb with magical medicinal value.
Panax notoginseng has been extensively employed in China to treat
microcirculatory disturbances, inflammation, trauma, internal and external
bleeding due to injury, and as a tonic. In recent years, with the deepening of
the research pharmacologically, many new functions have been discovered. This
review will introduce its pharmacological function on lifespan extension, anti
vascular aging, anti-brain aging, and anti-cancer properties, aiming to lay the
ground for fully elucidating the potential mechanisms of Panax notoginseng's anti
aging effect to promote its clinical application.
PMID- 29344414
TI - Herba Cistanches: Anti-aging.
AB - The Cistanche species ("Rou Cong Rong" in Chinese) is an endangered wild species
growing in arid or semi-arid areas. The dried fleshy stem of Cistanches has been
used as a tonic in China for many years. Modern pharmacological studies have
since demonstrated that Herba Cistanches possesses broad medicinal functions,
especially for use in anti-senescence, anti-oxidation, neuroprotection, anti
inflammation, hepatoprotection, immunomodulation, anti-neoplastic, anti
osteoporosis and the promotion of bone formation. This review summarizes the up
to-date and comprehensive information on Herba Cistanches covering the aspects of
the botany, traditional uses, phytochemistry and pharmacology, to lay ground for
fully elucidating the potential mechanisms of Herba Cistanches' anti-aging effect
and promote its clinical application as an anti-aging herbal medicine.
PMID- 29344415
TI - Rhizoma Coptidis and Berberine as a Natural Drug to Combat Aging and Aging
Related Diseases via Anti-Oxidation and AMPK Activation.
AB - Aging is the greatest risk factor for human diseases, as it results in cellular
growth arrest, impaired tissue function and metabolism, ultimately impacting life
span. Two different mechanisms are thought to be primary causes of aging. One is
cumulative DNA damage induced by a perpetuating cycle of oxidative stress; the
other is nutrient-sensing adenosine monophosphate-activated protein kinase (AMPK)
and rapamycin (mTOR)/ ribosomal protein S6 (rpS6) pathways. As the main bioactive
component of natural Chinese medicine rhizoma coptidis (RC), berberine has
recently been reported to expand life span in Drosophila melanogaster, and
attenuate premature cellular senescence. Most components of RC including
berberine, coptisine, palmatine, and jatrorrhizine have been found to have
beneficial effects on hyperlipidemia, hyperglycemia and hypertension aging
related diseases. The mechanism of these effects involves multiple cellular
kinase and signaling pathways, including anti-oxidation, activation of AMPK
signaling and its downstream targets, including mTOR/rpS6, Sirtuin1/ forkhead box
transcription factor O3 (FOXO3), nuclear factor erythroid-2 related factor-2
(Nrf2), nicotinamide adenine dinucleotide (NAD+) and nuclear factor-kappaB (NF
kappaB) pathways. Most of these mechanisms converge on AMPK regulation on
mitochondrial oxidative stress. Therefore, such evidence supports the possibility
that rhizoma coptidis, in particular berberine, is a promising anti-aging natural
product, and has pharmaceutical potential in combating aging-related diseases via
anti-oxidation and AMPK cellular kinase activation.
PMID- 29344416
TI - Lycium Barbarum: A Traditional Chinese Herb and A Promising Anti-Aging Agent.
AB - Lycium barbarum has been used in China for more than 2,000 years as a traditional
medicinal herb and food supplement. Lycium barbarum contains abundant Lycium
barbarum polysaccharides (LBPs), betaine, phenolics, carotenoids (zeaxanthin and
beta-carotene), cerebroside, 2-O-beta-d-glucopyranosyl-l-ascorbic acid (AA
2betaG), beta-sitosterol, flavonoids and vitamins (in particular, riboflavin,
thiamine, and ascorbic acid). LBPs are the primary active components of Lycium
barbarum. In this review, we discuss the pharmacological activities of LBPs and
other major components. They have been reported to mediate significant anti-aging
effects, through antioxidant, immunoregulative, anti-apoptotic activities and
reducing DNA damage. Thus, the basic scientific evidence for anti-aging effects
of LBPs is already available. However, additional studies are needed to
understand mechanisms by which LBPs mediate anti-aging properties. Novel findings
from such studies would likely pave the way for the clinical application of
traditional chinese medicine Lycium barbarum in modern evidence-based medicine.
PMID- 29344417
TI - The Effect of Traditional Chinese Medicine on Neural Stem Cell Proliferation and
Differentiation.
AB - Neural stem cells (NSCs) are special types of cells with the potential for self
renewal and multi-directional differentiation. NSCs are regulated by multiple
pathways and pathway related transcription factors during the process of
proliferation and differentiation. Numerous studies have shown that the compound
medicinal preparations, single herbs, and herb extracts in traditional Chinese
medicine (TCM) have specific roles in regulating the proliferation and
differentiation of NSCs. In this study, we investigate the markers of NSCs in
various stages of differentiation, the related pathways regulating the
proliferation and differentiation, and the corresponding transcription factors in
the pathways. We also review the influence of TCM on NSC proliferation and
differentiation, to facilitate the development of TCM in neural regeneration and
neurodegenerative diseases.
PMID- 29344418
TI - Advances in the Studies of Ginkgo Biloba Leaves Extract on Aging-Related
Diseases.
AB - The prevalence of degenerative disorders in public health has promoted in-depth
investigations of the underlying pathogenesis and the development of new
treatment drugs. Ginkgo biloba leaves extract (EGb) is obtained from Ginkgo
biloba leaves and has been used for thousands of years. In recent decades, both
basic and clinical studies have established the effects of EGb. It is widely used
in various degenerative diseases such as cerebrovascular disease, Alzheimer's
disease, macroangiopathy and more. Here, we reviewed several pharmacological
mechanisms of EGb, including its antioxidant properties, prevention of
mitochondrial dysfunctions, and effect on apoptosis. We also described some
clinical applications of EGb, such as its effect on neuro and cardiovascular
protection, and anticancer properties. The above biological functions of EGb are
mainly focused on aging-related disorders, but its effect on other diseases
remains unclear. Thus, through this review, we aim to encourage further studies
on EGb and discover more potential applications.
PMID- 29344419
TI - Dendrobium: Sources of Active Ingredients to Treat Age-Related Pathologies.
AB - Dendrobium represents one of the most important orchid genera, ornamentally and
medicinally. Dendrobiums are sympodial epiphytic plants, which is a name they are
worthy of, the name coming from Greek origin: "dendros", tree, and "bios", life.
Dendrobium species have been used for a thousand years as first-rate herbs in
traditional Chinese medicine (TCM). They are source of tonic, astringent,
analgesic, antipyretic, and anti-inflammatory substances, and have been
traditionally used as medicinal herbs in the treatment of a variety of disorders,
such as, nourishing the stomach, enhancing production of body fluids or
nourishing Yin. The Chinese consider Dendrobium as one of the fifty fundamental
herbs used to treat all kinds of ailments and use Dendrobium tonic for longevity.
This review is focused on main research conducted during the last decade (2006
2016) on Dendrobium plants and their constituents, which have been subjected to
investigations of their pharmacological effects involving anticancer, anti
diabetic, neuroprotective and immunomodulating activities, to report their
undeniable potential for treating age-related pathologies.
PMID- 29344420
TI - The Effects of Baicalin and Baicalein on Cerebral Ischemia: A Review.
AB - Ischemic stroke, producing a high mortality and morbidity rate, is a common
clinical disease. Enhancing the prevention and control of ischemic stroke is
particularly important. Baicalin and its aglycon baicalein are flavonoids
extracted from Scutellaria baicalensis, an important traditional Chinese herb. In
recent years, a growing body of evidences has shown that baicalin and baicalein
could be effective in the treatment of cerebral ischemia. Pharmacokinetic studies
have shown that baicalin could penetrate the blood-brain barrier and distribute
in cerebral nuclei. Through a variety of in vitro and in vivo models of ischemic
neuronal injury, numerous studies have demonstrated that baicalin and baicalein
have salutary effect for neuroprotection. Especially, the studies on the
pharmacological mechanism showed that baicalin and baicalein have several
pharmacological activities, which include antioxidant, anti-apoptotic, anti
inflammatory and anti-excitotoxicity effects, protection of the mitochondria,
promoting neuronal protective factors expression and adult neurogenesis effects
and many more. This review focuses on the neuroprotective effects of baicalin and
baicalein in ischemia or stroke-induced neuronal cell death. We aimed at
collecting all important information regarding the neuroprotective effect and its
pharmacological mechanism of baicalin and baicalein in various in vivo and in
vitro experimental models of ischemic neuronal injury.
PMID- 29344422
TI - The Effects of Physical Training are Varied and Occur in an Exercise Type
Dependent Manner in Elderly Men.
AB - Regular exercise can decrease the deleterious effects of aging and limit the
development and progression of chronic disease in elderly people, depending on
the type, intensity, frequency, and duration of exercise. This study aimed to
investigate the potential protective effects of different physical training
programs on oxidative stress parameters and inflammatory and neurotrophic
mediators in the serum of elderly men. Healthy male volunteers [60 to 80 years;
n=55] were divided into four groups: control [Ctr, n=14], aerobic training on dry
land [ATdl, n=12]; and combined training on dry land [CTdl, n=12] or in water
[CTw, n=17]. The training protocols were performed over 8 weeks, three times per
week. Each 1 h session included 5 min warming-up exercise, 50 min specific
training [aerobic, strength, or combined], and 5 min stretching. Blood samples
were drawn 72 h before [baseline] the beginning of the 8 weeks' protocol and 48 h
after the last training session, processed, and the serum was aliquoted and
stored at -70 degrees C until biochemical assessment of oxidative damage,
antioxidant system and neurotrophic, growth and inflammatory factors. Elevated
BDNF or IGF-1 levels were observed in the ATdl or CTdl groups, respectively.
Overall oxidative stress parameters were improved including reduced lipid
oxidative damage and increased thioredoxin reductase and glutathione peroxidase
activities and total glutathione. Significant decreases in the inflammatory
mediators IL-6 and IL-8 were observed; IL-6 was more susceptible to the effects
of type of physical training. Thus, the effects of training in elderly men vary
in an exercise type-dependent manner.
PMID- 29344424
TI - Letters to the Editor.
PMID- 29344423
TI - Age-Related Gray and White Matter Changes in Normal Adult Brains.
AB - Normal aging is associated with both structural changes in many brain regions and
functional declines in several cognitive domains with advancing age. Advanced
neuroimaging techniques enable explorative analyses of structural alterations
that can be used as assessments of such age-related changes. Here we used voxel
based morphometry (VBM) to investigate regional and global brain volume
differences among four groups of healthy adults from the IXI Dataset: older
females (OF, mean age 68.35 yrs; n=69), older males (OM, 68.43 yrs; n=66), young
females (YF, 27.09 yrs; n=71), and young males (YM, 27.91 yrs; n=71), using 3D T1
weighted MRI data. At the global level, we investigated the influence of age and
gender on brain volumes using a two-way analysis of variance. With respect to
gender, we used the Pearson correlation to investigate global brain volume
alterations due to age in the older and young groups. At the regional level, we
used a flexible factorial statistical test to compare the means of gray matter
(GM) and white matter (WM) volume alterations among the four groups. We observed
different patterns in both the global and regional GM and WM alterations in the
young and older groups with respect to gender. At the global level, we observed
significant influences of age and gender on global brain volumes. At the regional
level, the older subjects showed a widespread reduction in GM volume in regions
of the frontal, insular, and cingulate cortices compared to the young subjects in
both genders. Compared to the young subjects, the older subjects showed a
widespread WM decline prominently in the thalamic radiations, in addition to
increased WM in pericentral and occipital areas. Knowledge of these observed
brain volume differences and changes may contribute to the elucidation of
mechanisms underlying aging as well as age-related brain atrophy and disease.
PMID- 29344421
TI - Anti-Aging Implications of Astragalus Membranaceus (Huangqi): A Well-Known
Chinese Tonic.
AB - Owing to a dramatic increase in average life expectancy and the Family Planning
program of the 1970s - 1990s, China is rapidly becoming an aging society.
Therefore, the investigation of healthspan-extending drugs becomes more urgent.
Astragalus membranaceus (Huangqi) is a major medicinal herb that has been
commonly used in many herbal formulations in the practice of traditional Chinese
medicine (TCM) to treat a wide variety of diseases and body disorders, or
marketed as life-prolonging extracts for human use in China, for more than 2000
years. The major components of Astragalus membranaceus are polysaccharides,
flavonoids, and saponins. Pharmacological research indicates that the extract
component of Astragalus membranaceus can increase telomerase activity, and has
antioxidant, anti-inflammatory, immunoregulatory, anticancer, hypolipidemic,
antihyperglycemic, hepatoprotective, expectorant, and diuretic effects. A
proprietary extract of the dried root of Astragalus membranaceus, called TA-65,
was associated with a significant age-reversal effect in the immune system. Our
review focuses on the function and the underlying mechanisms of Astragalus
membranaceus in lifespan extension, anti-vascular aging, anti-brain aging, and
anti-cancer effects, based on experimental and clinical studies.
PMID- 29344425
TI - A Case of Psychosis in a Patient with Secondary Adrenal Insufficiency: A Possible
Etiological Role of a Hypocortisolemic-induced Increase in Proinflammatory
Cytokines.
AB - Adrenal insufficiency is divided into three types based on the etiology of its
development. In primary adrenal insufficiency, pathology resides in end-organ
failure at the level of the adrenal cortex, while in secondary and tertiary
adrenal insufficiency, impairment rests in the pituitary gland and hypothalamus,
respectively. Regardless of etiology, adrenal insufficiency results in a
hypocortisolemic condition. While the relationship between neuropsychiatric
symptoms, especially psychosis, and hypercortisolemia has been extensively
documented, the development of hypocortisolemia-induced psychosis is less common.
We present a case of secondary adrenal insufficiency caused by a pituitary tumor.
During the course of evaluation and treatment, the patient developed a psychotic
episode. We will briefly review the condition of adrenal insufficiency and
propose how hypocortisolemia can result in psychosis.
PMID- 29344426
TI - ZIKA MICROCEPHALY.
PMID- 29344427
TI - Top 10 Myths about Telepsychiatry.
AB - This ongoing column is dedicated to providing information to our readers on
managing legal risks associated with medical practice. We invite questions from
our readers. The answers are provided by PRMS, Inc. (www.prms.com), a manager of
medical professional liability insurance programs with services that include risk
management consultation, education and onsite risk management audits, and other
resources to healthcare providers to help improve patient outcomes and reduce
professional liability risk. The answers published in this column represent those
of only one risk management consulting company. Other risk management consulting
companies or insurance carriers may provide different advice, and readers should
take this into consideration. The information in this column does not constitute
legal advice. For legal advice, contact your personal attorney. Note: The
information and recommendations in this article are applicable to physicians and
other healthcare professionals so "clinician" is used to indicate all treatment
team members.
PMID- 29344428
TI - Introduction to Special Issue: Disability, Work and Representation: New
Perspectives.
PMID- 29344429
TI - Pathway Analysis of Gene Expression of E14 Versus E18 Fetal Fibroblasts.
AB - Objective: Fetuses early in gestation heal skin wounds without forming scars. The
biological mechanisms behind this process are largely unknown. Fibroblasts,
however, are cells known to be intimately involved in wound healing and scar
formation. We examined fibroblasts in different stages of development to
characterize differences in gene expression that may result in the switch from
regenerative wound repair to repair with scarring. Approach: Fibroblasts were
isolated and cultured from the back skin of BALB/c wild-type mouse fetuses at
embryonic day (E)14 and E18 (n = 10). The fibroblast total RNA was extracted, and
microarray analysis was conducted using chips containing 42,000 genes.
Significance analysis of microarrays was performed to identify genes with greater
than twofold expression difference and a false discovery rate of less than two.
Identified genes subsequently underwent enrichment analysis to detect
differentially expressed pathways. Results: Two hundred seventy-five genes were
differentially expressed between E14 and E18 in fetal fibroblasts. Thirty genes
were significantly downregulated and 245 genes were significantly upregulated at
E18 compared with E14. Ingenuity pathway analysis identified the top 20 signaling
pathways differentially activated in fetal fibroblasts between the E18 and E14
time points. Innovation: To our knowledge, this work represents the first
instance where differentially expressed genes and signaling pathways between
fetal fibroblasts at E14 and E18 have been studied. Conclusion: The genes and
pathways identified here potentially underlie the mechanism behind the transition
from fetal wound healing via regeneration to wound healing by repair, and may
prove to be key targets for future therapeutics.
PMID- 29344430
TI - An Improved Humanized Mouse Model for Excisional Wound Healing Using Double
Transgenic Mice.
AB - Objective: Splinting full-thickness cutaneous wounds in mice has allowed for a
humanized model of wound healing. Delineating the epithelial edge and assessing
time to closure of these healing wounds via macroscopic visualization have
remained a challenge. Approach: Double transgenic mice were created by
crossbreeding K14-Cre and ROSAmT/mG reporter mice. Full-thickness excisional
wounds were created in K14-Cre/ROSAmT/mG mice (n = 5) and imaged using both
normal and fluorescent light on the day of surgery, and every other postoperative
day (POD) until wound healing was complete. Ten blinded observers analyzed a
series of images from a single representative healing wound, taken using normal
or fluorescent light, to decide the POD when healing was complete. K14
Cre/ROSAmT/mG mice (n = 4) were subsequently sacrificed at the four potential
days of rated wound closure to accurately determine the histological point of
wound closure using microscopic fluorescence imaging. Results: Average time to
wound closure was rated significantly longer in the wound series images taken
using normal light, compared with fluorescent light (mean POD 13.6 vs. 11.6, *p =
0.008). Fluorescence imaging of histological samples indicated that
reepithelialization was complete at 12 days postwounding. Innovation: We describe
a novel technique, using double transgenic mice K14-Cre/ROSAmT/mG and
fluorescence imaging, to more accurately determine the healing time of wounds in
mice upon macroscopic evaluation. Conclusion: The accuracy by which wound healing
can be macroscopically determined in vivo in mouse models of wound healing is
significantly enhanced using K14-Cre/ROSAmT/mG double transgenic mice and
fluorescence imaging.
PMID- 29344431
TI - Noncoding RNAs in Wound Healing: A New and Vast Frontier.
AB - Significance: Wound healing requires a highly orchestrated coordination of
processes that are not yet fully understood. Therefore, available clinical
therapies are thus far limited in their efficacy in preventing and treating both
chronic wounds and scars. Current gene-based therapeutics is largely based on our
understanding of the protein-coding genome and proteins involved in known wound
healing pathways. Recent Advances: Noncoding RNAs such as microRNAs and long
noncoding RNAs have recently been found to be significant modulators of gene
expression in diverse cellular pathways. Research has now implicated noncoding
RNAs in nearly every stage of the wound healing process, suggesting that they may
serve as clinical therapeutic targets. Noncoding RNAs are critical regulators in
processes such as angiogenesis and cutaneous cell migration and proliferation,
including classically described biological pathways previously attributed to
mostly protein constituents. Critical Issues: The complexity and diversity of the
interactions of noncoding RNAs with their targets and other binding partners
require thorough characterization and understanding of their functions before
they may be altered to modulate human wound healing pathways. Future Directions:
Research in the area of noncoding RNAs continues to rapidly expand our
understanding of their potential roles in physiological and pathological wound
healing. Coupled with improving technologies to enhance or suppress target
noncoding RNA in vivo, these advances hold great promise in the development of
new therapies for wound healing.
PMID- 29344433
TI - One Click Away: Digital Mentorship in the Modern Era.
AB - Mentorship is a valuable component of the career development of junior faculty.
The digital era has allowed for greater access to mentors spanning geographic
barriers and time zones. This article discusses the concept of digital
mentorship, as well as strategies and techniques for developing and supporting a
digital mentoring relationship in the modern era.
PMID- 29344432
TI - WT1 peptide vaccine in Montanide in contrast to poly ICLC, is able to induce WT1
specific immune response with TCR clonal enrichment in myeloid leukemia.
AB - Background: The optimal strategy for vaccination to induce CD8+ T cell responses
against WT1 is not known. Methods: A pilot randomized study in HLA-A02+ patients
to receive vaccination with WT1 in Montanide or in poly ICLC, a TLR3 agonist, to
explore the novel immune adjuvant was conducted. Seven patients were randomized.
Four patients received WT1 in Montanide, and three with WT1 in poly ICLC. Five
patients were in morphologic remission and two had residual morphologic disease
at the study entry. Results: All patients finished the induction phase without
any major toxicity except mild transient local injection reaction. One patient on
the Montanide arm developed aseptic ulceration at two vaccine sites which healed
without antibiotics. Three of 4 patients on the Montanide arm had a decreased
expression of WT1 after WT1 vaccination, and two of them demonstrated generation
of WT1-specific cytotoxic CD8+ T cell responses with biased TCR beta chain
enrichment. In contrast, no obvious WT1-specific immune responses were detected
in two patients on the poly ICLC arm, nor was there clonal enrichment by TCR
alpha/beta sequencing; however, these patients did also have decreased WT1
expression and remained in remission several years after the initiation of
treatment. Conclusions: WT1 peptide vaccine with Montanide as an adjuvant induces
detectable WT1-specific CD8+ T cell responses with clonal TCR enrichment, which
may be capable of controlling leukemia recurrence in the setting of minimal
residual disease. Poly ICLC may induce anti-leukemic activity in the absence of
detectable WT1 specific CD8+ T cell responses.Trial registration NCT01842139,
7/3/2012 retrospectively registered;
https://clinicaltrials.gov/ct2/show/NCT01842139.
PMID- 29344434
TI - Rare Multidrug-Resistant Pulmonary Nocardiosis in AIDS.
AB - Nocardiosis is an opportunistic infection in patients with depressed cell
mediated immunity. Inhalation is the primary route for exposure via dust
particles. Patients with acquired immune deficiency syndrome (AIDS) are at
increased risk of disseminated disease. A challenge in the diagnosis of pulmonary
nocardiosis is that it can mimic other pulmonary diseases. Nocardia farcinica
tends to be a more virulent, multidrug-resistant strain with an increased
tendency to disseminate. This report describes a 64-year-old man with AIDS found
to have pulmonary nocardiosis that did not respond to standard antibiotic
therapy. Further evaluation revealed the virulent, multidrug-resistant Nocardia
farcinica species. Targeted antibiotic therapy was initiated, after which the
patient had an improvement in pulmonary symptoms. It is important to suspect
pulmonary nocardiosis in immunocompromised patients who fail to respond to
standard antimicrobial therapy. Susceptibilities should be obtained so that
appropriate therapy can be promptly initiated as Nocardia farcinica is highly
resistant to multiple antimicrobials.
PMID- 29344435
TI - Synchronous Uterine Metastases from Breast Cancer: Case Study and Literature
Review.
AB - Breast cancer rarely metastasizes to the uterus. Here, we report two breast
cancer patients with synchronous metastases to the uterus. Case 1 highlights a 46
year-old female with invasive ductal carcinoma who presented with a breast mass
and was found to have uterine enlargement on positron emission tomography (PET)
scan. Biopsy revealed a metastatic 4 mm focus of breast cancer in the background
of endometrial hyperplasia. Case 2 reports a 62-year-old postmenopausal female
diagnosed with lobular carcinoma of the breast following an abnormal screening
mammogram. A routine pap smear necessitated further workup, revealing
simultaneous endometrial and cervical metastasis. Both patients did not have any
gynecologic symptoms and presented a diagnostic challenge.
PMID- 29344436
TI - Exploring Laser-Induced Breakdown Spectroscopy as a Potential Tool in Mohs
Micrography: A Mini Review.
AB - Mohs micrographic surgery is the technique of surgically removing skin tumors by
gradually excising thin layers and visualizing under a microscope till a tumor
free zone is obtained. During the surgical procedure, visible tumors are
surgically removed. During the second stage, if tumor margins are clear with the
positive specimen at depth, only depth cavitations need to be done without
altering the tumor diameter. Defining the depth during this procedure is a major
challenge due to the nonexistence of proper guidelines. Using the laser-induced
breakdown spectroscopy (LIBS) technique, depth profiling can be performed
precisely, preventing excessive tissue removal and reducing time consumption
during the microscopic examination.
PMID- 29344437
TI - Rhabdomyolysis in a Patient Taking Both Oxandrolone for Bodybuilding and
Methamphetamine.
AB - Nonprescription drug use is increasingly prevalent in the United States. We
report a case of a 31-year-old male who presented with hallucinations and was
found to have rhabdomyolysis. He was consuming oxandrolone for six weeks and
ingested methamphetamine the night prior to presentation. With supportive
treatment, including intravenous hydration, the patient's mental status returned
to baseline and rhabdomyolysis resolved. Our case illustrates the need to
understand the interaction between different illicit substances. More research
needs to be done to further understand the reactions between different
medications as patients consume different combinations of substances.
PMID- 29344440
TI - HIV assessment and testing for hospital in-patients: still a weak link in the
cascade.
PMID- 29344438
TI - New Therapeutic Approaches in Obesity and Metabolic Syndrome Associated with
Polycystic Ovary Syndrome.
AB - Polycystic ovary syndrome (PCOS) is a pathophysiological disorder affecting
reproductive and metabolic indices. PCOS is commonly associated with a high
prevalence of insulin resistance and obesity; this association carries an
increased risk of developing metabolic syndrome, type 2 diabetes mellitus (T2DM),
and cardiovascular disease. Guidelines recommend lifestyle modification,
metformin, hormonal contraceptives (HCs), and bariatric surgery as the main
treatment options in obese patients with PCOS. Studies are being conducted to
test the efficacy of existing treatment options as well as to discover new
therapies. This review focuses on the most recent advances in this regard and
highlights new hypotheses and emerging studies to give a picture of the latest
therapeutic trends in the treatment of obese patients with PCOS. In this respect,
much attention is given to the role of inositols, the mediators of insulin
action. A deficiency of d-chiro-inositol containing inositol-phospho-glycans may
be the basis of insulin resistance frequently seen in PCOS patients. Moreover,
evidence suggests the use of statins in obese women with PCOS, but guidelines
call for further research. Adiponectin, quercetin, vitamin D, and anti-obesity
drugs have also been studied and seem to have a useful role in the treatment of
obesity and metabolic syndrome in PCOS. Many trials have been conducted on the
use of non-pharmacological therapies. Therapies including resveratrol,
acupuncture, and berberine have favorable effects in overweight PCOS patients.
However, more research is needed to reveal the clinical complexity of PCOS and
develop more effective treatment options.
PMID- 29344441
TI - Protecting those who care for others.
PMID- 29344439
TI - Regiochemical Control in Triptycene Formation-An Exercise in Subtle Balancing
Multiple Factors.
AB - Reactions between 1,8-dichloroanthracenes with substituents in position 10 and
ortho-chloroaryne afford mixtures of 1,8,13- (syn) and 1,8,16
trichlorotriptycenes (anti). The syn/anti ratio is dependent on these
substituents. Electropositive substituents like SiMe3 and GeMe3 lead to preferred
formation of the syn-isomer, whereas CMe3 groups exclusively afford the anti
isomer. Different quantum chemical calculations including location of transition
states give conflicting results, but indicate the importance of dispersion forces
for an at least qualitative prediction of results. The syn-trichlorotriptycenes
with SiMe3 and GeMe3 substituents were characterized by using NMR spectroscopy,
mass spectrometry, and X-ray diffraction experiments.
PMID- 29344442
TI - Active tuberculosis case finding in India: need for introspection.
PMID- 29344443
TI - Outcomes of patients treated with individualised anti-tuberculosis regimens in a
tertiary care centre in India.
PMID- 29344444
TI - Addressing deprivation of liberty, human mobility and tuberculosis in 2018.
PMID- 29344446
TI - Global Optimal PEEP for Anesthetized Patients.
PMID- 29344445
TI - Comparing Postoperative Complications and Inflammatory Markers Using Total
Intravenous Anesthesia Versus Volatile Gas Anesthesia for Pancreatic Cancer
Surgery.
AB - Objectives: The objective of this study is to evaluate postoperative
complications and inflammatory profiles when using a total intravenous anesthesia
(TIVA) or volatile gas-opioid (VO) based anesthesia in patients undergoing
pancreatic cancer surgery. Methods: Design, retrospective propensity score
matched cohort; Setting, major academic cancer hospital; Patients, all patients
who had pancreatic surgery between November 2011 and August 2014 were
retrospectively reviewed. Propensity score matched patient pairs were formed. A
total of 134 patients were included for analysis with 67 matched pairs;
Interventions, Patients were categorized according to type of anesthetic used
(TIVA or VO). Patients in the TIVA group received preoperative celecoxib,
tramadol, and pregabalin in addition to intraoperative TIVA with propofol,
lidocaine, ketamine, and dexmedetomidine. The VO-group received a volatile-opioid
based anesthetic; Measurements, demographic, perioperative clinical data,
platelet lymphocyte ratios, and neutrophil lymphocyte ratios were collected.
Complications were graded and collected prospectively and later reviewed
retrospectively. Results: Patients receiving TIVA were more likely to have no
complication or a lower grade complication than the VO-group (P = 0.014). There
were no differences in LOS or postoperative inflammatory profiles noted between
the TIVA and VO groups. Conclusions: In this retrospective matched analysis of
patients undergoing pancreatic cancer surgery, TIVA was associated with lower
grade postoperative complications. Length of hospital stay (LOS) and
postoperative inflammatory profiles were not significantly different.
PMID- 29344447
TI - Successful Management of Right Ventricular Perforation Associated with a
Pacemaker Lead During Off-Pump CABG Surgery: A Case Report.
AB - Introduction: Intraoperative right ventricular perforation due to pacing catheter
after its successful and uneventful insertion is a rare complication. Here, we
present a case of cardiac arrest due to right ventricular perforation associated
with a pacemaker lead during off-pump coronary artery bypass graft surgery. Case
Presentation: The case was a 68-year-old male, who was admitted to our hospital
with retrosternal chest pain. He had a history of implantation of a permanent
pacemaker due to symptomatic complete atrioventricular block. Based on
angiography, the diagnosis was 3- vessel disease involving the left anterior
descending, second obtuse marginal, and right coronary arteries. The right
ventricle was perforated by the tip of the permanent pacemaker lead during off
pump coronary artery bypass graft surgery. Subsequently, the patient suddenly
experienced cardiac arrest and underwent emergency on-pump cardiac surgery.
Conclusions: This case showed that in some situations, emergency surgery as a
life saving procedure may be required in cardiac perforation due to permanent
pacemaker lead even following cardiac arrest.
PMID- 29344448
TI - Learning Theories: The Basics to Learn in Medical Education.
PMID- 29344449
TI - Motivating Students for Project-based Learning for Application of Research
Methodology Skills.
AB - Introduction: Project-based learning (PBL) is motivational for students to learn
research methodology skills. It is a way to engage and give them ownership over
their own learning. Aims and Objectives: The aim of this study is to use PBL for
application of research methodology skills for better learning by encouraging an
all-inclusive approach in teaching and learning rather than an individualized
tailored approach. Methodology: The present study was carried out for MBBS 6th-
and 7th-semester students of community medicine. Students and faculties were
sensitized about PBL and components of research methodology skills. They worked
in small groups. The students were asked to fill the student feedback
Questionnaire and the faculty was also asked to fill the faculty feedback
Questionnaire. Both the Questionnaires were assessed on a 5 point Likert scale.
After submitted projects, document analysis was done. Results: A total of 99
students of the 6th and 7th semester were participated in PBL. About 90.91%
students agreed that there should be continuation of PBL in subsequent batches.
73.74% felt satisfied and motivated with PBL, whereas 76.77% felt that they would
be able to use research methodology in the near future. Conclusions: PBL requires
considerable knowledge, effort, persistence, and self-regulation on the part of
the students. They need to devise plans, gather information evaluate both the
findings, and their approach. Facilitator plays a critical role in helping
students in the process by shaping opportunity for learning, guiding students,
thinking, and helping them construct new understanding.
PMID- 29344450
TI - Hybrid Tool for Assessment of Professionalism among Dental Undergraduate
Students.
AB - Context: Of the several methods available for assessment of professionalism,
there is still no consensus on an ideal tool for dental undergraduate (UG)
students. Aims: The study aims to use a hybrid tool for assessment of
professionalism among dental undergraduate students. Settings and Design: Cross
sectional design with purposive sampling. Subjects and Methods: All final year UG
dental students participated in this study. Evaluation of knowledge about
professionalism was through written test. Professional behavior of each final
year student in a clinical setting was assessed with a prevalidated questionnaire
of multisource feedback (MSF). The scores of written test and the MSF were
calculated for each student. Data were analyzed to evaluate scores of knowledge
and MSF scores as per assessor category. Correlation between knowledge scores and
MSF was evaluated. Student perceptions were taken toward assessment of
professionalism. Statistical Analysis Used: Statistical analysis was done using
descriptive statistics. Pearson's coefficient was used to determine the
correlation between average knowledge scores and the MSF scores. Results:
Knowledge scores were significantly more for female students (P < 0.05, t-test).
Patients rated the students highest. Correlation between knowledge and MSF scores
was found to be statistically significant (Pearson's correlation, P < 0.01).
Students gave feedback that assessment of professionalism should be done from the
beginning of the clinical years. Conclusions: Evaluation revealed that knowledge
toward professionalism correlated with the professional behavior implying
association between knowledge and reasons for a particular action.
PMID- 29344451
TI - Evaluation of Brainstorming Session as a Teaching-learning Tool among
Postgraduate Medical Biochemistry Students.
AB - Background: The thrust for postgraduate teaching should be self-directed learning
with equal participation by all students in academic discussions. Group
discussions involve conduction of the discourse by a leader who guides the
discussion as well as points out any wrong information. This discourages quieter
students from participation with the fear of rebuke. Brainstorming is devoid of
all such fallacies with no judgment and reprimand. Aim: The aim of this study was
to use brainstorming as a teaching-learning tool among postgraduate students of
medical biochemistry. Materials and Methods: The project was commenced after due
approvals from the research and ethical committee. The participants were enrolled
after informed consent and sensitization. All the pro forma and questionnaires
were duly validated by experts. After piloting and incorporation of the
suggestions for improvisation, the main sessions were planned and implemented.
The response was judged by posttest scores and feedback forms. Results: There was
an improvement of understanding of the biochemical concepts as assessed by the
posttest scores and solving of a similar clinical problem. The students expressed
satisfaction with the conduction, timing, and discussion of the clinical
problems. The drawbacks of traditional teaching as expressed during the feedback
stage were also taken care of by the brainstorming sessions. Conclusions: Our
project made the students and the faculty aware about the utility of
brainstorming for teaching purposes in medical education which till now was
considered efficacious only for troubleshooting in advertising and management
institutions. The students were satisfied with this technique for understanding
of biochemical concepts.
PMID- 29344452
TI - The Acceptability and Feasibility of Mini-clinical Evaluation Exercise as a
Learning Tool for Pediatric Postgraduate Students.
AB - Background: The mini-clinical evaluation exercise (Mini-CEX) is a valid and
reliable tool that facilitates the assessment of skills essential for a physician
and provision of immediate feedback. Aims: This study aimed to assess the
acceptability and feasibility of Mini-CEX as a learning tool for pediatric
residents. Materials and Methods: Following the sensitization with the concept of
Mini-CEX, the actual process of assessment of residents was done using the
"standardized American Board of Internal Medicine Mini-CEX evaluation form."
Feedback about the Mini-CEX was taken from the residents and faculty on separate
questionnaires consisting of close- and open-ended questions. A total of 87 Mini
CEX encounters were done with 13 faculty and 29 residents over 6-month study
period. Results: Residents perceived that it is a method that does the assessment
of skills, prerequisite for good clinical performance with provision of immediate
feedback. Most of the residents felt that it improved their clinical skills,
uplifted the personal development, and impart a better one to one student-teacher
interaction. Almost all the faculty were satisfied with this method of
assessment. They found it useful for improved learning of themselves also. Both
residents and faculty suggested to incorporate Mini-CEX in curriculum.
Conclusions: Mini-CEX is an acceptable learning tool as reflected by the
residents and faculty. It is feasible to use mini-CEX for assessment of
residents.
PMID- 29344453
TI - Introduction of Medical Humanities in MBBS 1st Year.
AB - Context: Most vital areas of patient management such as empathy, professionalism,
and ethics are lacking in fresh undergraduates. These areas are considered to be
part of hidden curriculum, and as these are not formally taught, we lack
competent medical graduates. Introduction of medical humanities (MH) early in the
medical curriculum can help to inculcate required soft skills. Aims: This study
aims to develop, administer, and evaluate MH module in 1st year MBBS students.
Settings and Design: Module of MH was introduced among 150 1st year MBBS medical
students. Subjects and Methods: After taking permission from ethical committee of
the institute, a core committee for development of MH module was formed. A
standardized validated module for MH comprising of three sessions was formed and
was introduced in 1st year MBBS 150 students. Evaluation was done in the form of
student and faculty feedback questionnaire, consisting of open- and closed-ended
questions. Statistical Analysis Used: Analysis was done using descriptive
statistics using mean and standard deviation. Results: According to participants'
feedback and perception, mean overall rating of MH module was 4.69, indicating
that it was received well by the students. Out of 3 sessions conducted, students
gave maximum grades to session 2: cinemeducation. Results of faculty feedback
questionnaire indicated that MH is needed and should be introduced in every batch
of 1st year MBBS and should be continued longitudinally. Conclusions: Awareness,
knowledge, and attitude of students improved as a result of MH module. Our
results indicate that such modules should be implemented in undergraduate medical
curriculum.
PMID- 29344454
TI - Critical Review of "Family Health Advisory Services" Assessment in MBBS Training
Program in Community Medicine.
AB - Context: Family Health Advisory Services (FHAS) posting as well as its assessment
is resource demanding but fails to enjoy priority. Study focuses on a holistic
overview of the assessment process to understand need for change. Aims: The aim
of this study is to identify perceived gaps in current assessment practices
related to FHAS posting. Settings and Design: A cross-sectional mixed method
study among all the V semester students currently undergoing assessment for the
posting, past students (selected VII semester students and interns), preceptors
(supervising residents - postgraduate students in department and senior resident,
health assistants, medical social service officer), and involved faculty. Subject
and Methods: Self-administered questionnaire, in-depth interview, focus group
discussions (two) as well as observations using checklist were used for data
collection and triangulation. Statistical Analysis Used: Quantitative data used
in this study were statistical measures of central tendency and dispersion.
Qualitative data transcript repeatedly read to identify underlying common themes,
compared to draw inference. Results: There was a lack of guidelines and
communication regarding assessment. Formative assessment was not performed and
replaced by one time end assessment. All components of learning were not
assessed. End-posting assessment was not standardized and unrelated to learning
objectives. Award of scores was skewed toward right for intervention and toward
left for analysis and community diagnosis. Conclusions: There is a need to focus
on proper implementation of programme to strengthen formative assessment.
Assessment should be relevant to learning objectives of posting. Faculty has to
lead by example.
PMID- 29344455
TI - Qualitative Assessment of Learning Strategies among Medical Students Using Focus
Group Discussions and In-depth Interviews.
AB - Background: Globally, students with top academic performance and high
intellectual capacity usually opt to study medicine. However, once students get
enrolled, their academic performance varies widely. Such variations appear to be
determined by various factors, one of them being types of learning strategies
adopted by students. The learning strategies utilized by the students with better
academic performance are likely to be more effective learning strategies. Aims
and Objectives: The objective is to identify effective learning strategies used
by medical students. Methodology: This study was carried out among the MBBS
students of Final Professional Part I. Students were categorized into three
groups namely: high, average, and low rankers based on overall academic
performance in second Professional University examination. First, a questionnaire
consisting of closed- and open-ended questions was administered to students, to
find their learning strategies. Subsequently, focus group discussion and in-depth
interviews were conducted for high- and low-rankers. Discussions were audio
recorded, transcribed, and analyzed. Key statements were highlighted, collated,
and categorized into general themes and sub-themes. Results: Evident themes which
emerged as effective strategies were hard work in the form of regularity of
studies, meticulous preparation of notes, constructive use of time, utilization
of e-learning, learning styles and deep learning approach and regular ward
visits. Intrinsic motivation, family support, balancing physical activities and
studies, guidance by seniors, teachers, dealing with nonacademic issues such as
language barriers and stress were also identified as important strategies.
Conclusions: Disseminating effective learning strategies in a systematic manner
may be helpful to students in achieving better academic outcomes. Furthermore,
educationists need to modulate their teaching strategies based on students'
feedback.
PMID- 29344456
TI - Early Clinical Exposure as a Learning Tool to Teach Neuroanatomy for First Year
MBBS Students.
AB - Context: Early clinical exposure (ECE) is one of the important tools to teach
basic science to the MBBS students. It is one form of vertical integration
between basic science and clinical subjects. This study is an effort at exploring
the use of ECE as a motivational tool toward better learning in neuroanatomy for
first year MBBS students. Aim: This study aims to make the students interested
and motivated to study neuroanatomy by using ECE as learning tool in neuroanatomy
and to make the students enable to retain the knowledge of neuroanatomy more
efficiently and correlate the knowledge of neuroanatomy with neuromedicine.
Settings and Design: This study was conducted in collaboration with the
Departments of Anatomy, General Medicine and Medical Education Unit in the year
2016. This was cross-sectional study. Subjects and Methods: One hundred and fifty
students of 1st Professional MBBS were subdivided into two groups. After
preliminary classes on brain, brainstem, and spinal cord for both groups,
conventional lecture classes were taken for Group A only on upper motor neuron
(UMN) and lower motor neuron (LMN) paralysis, and only Group B visited General
Medicine ward where HOD, General Medicine showed and examined patients of UMN
paralysis and LMN paralysis, elicited different symptoms, and discussed different
investigation. It was followed by assessment of all by problem-based multiple
choice questions (MCQ) and short answer questions. Then, Group B attended lecture
class on different cranial nerve palsy whereas Group A visited medicine ward. It
was followed by assessment of both groups by problem-based MCQ and short answer
questions. The performance was compared. Then, the feedback of the students on
ECE was collected by means of reflection writing followed by administration of
questionnaire. Then, the perception of teachers regarding ECE was recorded by
focused group discussion. Statistical Analysis Used: Student's t-test was used to
compare the performance of both batches. Reflection writing and focus group
discussion were analyzed qualitatively. Results: There was a significant
difference in Group A (P = 0.019) but no significant difference in Group B (P =
0.679). All the teachers opined that ECE was an efficient method but more time
and interdepartmental collaboration were necessary. Conclusions: Group A improved
performance due to ECE but Group B maintained the motivational effect of it.
Therefore, ECE can be used as an effective learning tool.
PMID- 29344457
TI - Development and Implementation of Module for Medical Graduates to Improve Socio
cultural Sensitivity towards People Living with HIV.
AB - Background: Health professionals are documented as an important cause for
stigmatizing people living with HIV (PLHIV). Since traditional teaching on HIV in
India does not address cultural competencies, medical graduates lack
sociocultural sensitiveness while addressing the health needs of PLHIV. Aim: The
aim of this study is to develop and to implement a module for medical graduates
to improve their sociocultural sensitivity toward PLHIV. Methodology: A module
was designed and introduced to address the core sensitive issues in HIV among
medical graduates with the help of trained faculty. It included community
education sessions including interaction with PLHIV to address cross-cultural
issues and understand their health needs. Feedback for the perception of faculty
and students was obtained. Knowledge and skills improvement was assessed through
pre- and post test and direct observation of procedural skills (DOPS). Results:
Mean feedback score was high for all the components covered by the module. It was
found to be more for "usefulness of module" (4.91 +/- 0.27836 on a scale of 5)
than other components of the module. Feedback by faculty showed almost perfect
agreement on "improvement of student's clinical skills" and "bringing perfection
in their future practice" across multiple raters. Multiple response open-ended
feedback showed, 78 (19%) responses affirmed improvement in communication skills
with training in this module. Pre- and post test mean score for knowledge showed
an increase (22.1 to 26.49). Mean skills improvement as per expectations were
86.81 and beyond expectations were 5.34. Conclusions: Training the medical
graduates in structured HIV specific module improves their socio-cultural
sensitivity toward PLHIV and is perceived useful.
PMID- 29344458
TI - Case-based Learning in Microbiology: Observations from a North West Indian
Medical College.
AB - Background: Microbiology is usually taught by conventional lectures, and its
retention and application is observed to be poor among medical
graduates/practitioners. Aim and Objectives: Introduction of case-based learning
(CBL) in microbiology for second-year professional MBBS students. Materials and
Methods: Students were divided into two groups of fifty each. Four clinical cases
were used for CBL. One group had two CBL sessions whereas the other had didactic
lectures (DLs) and then the groups were crossed over. Case scenario handouts were
given to students a week before the session, and smaller groups were formed for
discussions and presentations in CBL sessions. Posttest, in multiple choice
questions format, was conducted in two phases: First, immediately after the
completion of the four CBL and DL sessions, and second, 6 weeks after the first
posttest. Student and faculty feedback was taken about CBL sessions. Results:
Hundred MBBS students of the fourth semester voluntarily participated in the CBL
study. The CBL scores were significantly higher than DL session scores (P =
0.015). This difference was more marked in scoring done after 6 weeks of session
completion (P < 0.001). Student reported satisfaction in being taught by CBL
method in 5-point Likert scale feedback form. Faculty feedback was positive for
CBL. Conclusions: CBL helped in retention of knowledge and its application better
than DL in our observation. More sessions on commonly encountered case scenarios
will be useful for students in recalling basic science knowledge in their later
years as practitioners.
PMID- 29344459
TI - Module for Interns in Medical Ethics: A Developmental Diegesis.
AB - Background: Media report is rife with incidences of doctor-patients' conflict,
and this partly is due to communication gap and unethical practices being adopted
by the doctors. Our regular curriculum fails to impart any training in ethical
issues in patient care. Imparting training to students in these soft-skills is
the need of the hour. Aim and Objectives: To develop a module for interns in
medical ethics (MIME) in patient care, validate it and pilot run the module for
standardization. Methodology: After conducting faculty development workshop in
curriculum designing and three rounds of Delphi with alumni, a module in medical
ethics was developed and peer validated. The questionnaire for pilot run,
questionnaire for future use of module delivery and pre- and post-test were also
peer validated. The module was delivered to 17 interns as pilot run in the form
of 4 days' workshop. After pilot run, the module was standardized to 10 broad
topics and 3 days' workshop. The questionnaire for future delivery of module in
regular routine was also validated during pilot run. Results: Twenty-five faculty
members participated in 1 day faculty development workshop and 59 alumni
completed three rounds of Delphi. After peer review by five experts, a module of
11 broad areas was developed and was pilot run on 17 interns. Based on the
feedback from pilot run, a standardized, validated 18 h teaching MIME in patient
care was developed. Conclusion: Pilot study proves that curriculum innovation in
the form of medical ethics training to interns; when as undergraduate students,
they actively participate in patient care under supervision will go a long way in
inculcating soft skills like ethics, compassion and communication in them.
PMID- 29344460
TI - Impact of Integrated Teaching Sessions for Comprehensive Learning and Rational
Pharmacotherapeutics for Medical Undergraduates.
AB - Background: It is postulated that integrated teaching method may enhance
retention of the knowledge and clinical applicability of the basic sciences as
compared to the didactic method. Aim: The present study was undertaken to compare
the integrated teaching method with the didactic method for the learning ability
and clinical applicability of the basic sciences. Materials and Methods: The 2nd
year MBBS students were divided into two groups randomly. The study was conducted
into two stages. In the first stage, conventional didactic lectures on
hypertension (HT) were delivered to one group and multidisciplinary integrated
teaching to another group. For the second stage, diabetes mellitus groups were
swapped. Retention of the knowledge between the groups were assessed through a
multiple choice questions (MCQ) test. Feedback of the students and faculty was
obtained on a 5 point Likert scale. For the comparison, student's data were
regrouped into four groups, i.e., integrated HT, didactic HT, integrated diabetes
and didactic diabetes. Results: There was no significant difference of MCQ score
between integrated HT, didactic HT, and integrated diabetes group. However, the
score obtained in didactic diabetes was significantly more (P = 0.00) than other
groups. Majority of the students favored integrated teaching for clinical
application of basic science and learning of the skill for the future clinical
practice. Faculties considered integrated method as a useful method and suggested
frequent use of this method. Conclusion: There was no clear difference in
knowledge acquisition; however, the students and faculties favored integrated
teaching method in the feedback questionnaire.
PMID- 29344461
TI - Using Role-plays as an Empathy Education Tool for Ophthalmology Postgraduate.
AB - Purpose: To assess the role of an "empathy sensitizing module" (ESM) in
ophthalmology postgraduates in promoting effective empathetic communication.
Methodology: Thirty-nine ophthalmology postgraduates were taught effective
empathetic communication using specially designed module, comprising of five
illustrative role-plays. We evaluated the impact of the training by (a) self
assessment of empathy quotient by residents using Jefferson Scale of Empathy (JSE
scale) before and 6 weeks after ESM training and (b) nonparticipant observation
(NPO) by trained faculty in real-life settings over the next 4 months. A peer
validated, self-designed checklist was used for NPO. The change in score was
analyzed using Student's paired t-test. The faculty observed the use of empathy
in real-life patient encounters of the trainees over the next 6 months. In
addition, secondary qualitative data were collected and analyzed to assess the
impact of the module on other stakeholders such as the role-playing undergraduate
students and core faculty. Results: Pretraining assessment revealed that concept
of empathy during patient communication was understood by only 10% students.
PostESM training, the self-rated mean empathy score, on JSE, significantly
increased from 95.9 to 106.7 (of a maximum of 140). This was also confirmed by a
significant improvement in externally rated empathy and soft skills scores (from
29.3 to 39.1; of a maximum of 55) using the NPO tool. Focus group discussion was
done on the continued display of empathy by the trainees in real-life situation
over 6 months of observation by the faculty. The group agreed that there was a
gradual attrition of initial gain in empathy behavior over the observation period
of 6 months. The spillover benefits of the training process were observed among
the role-playing undergraduates as well. A thematic analysis of their reflections
on the process revealed a substantial change with an improved understanding of
effective communication. Conclusions: There is a definite scope for introducing
empathetic communication in medical training. Empathetic communication can be
improved by effective training in a contextual manner with a need for regular
reinforcement. Sensitization at all levels including the faculty is required to
implement effective communication skills in medical profession.
PMID- 29344462
TI - Introducing Mentoring to 1st-year Medical Students of a Private Medical College
in North India: A Pilot Study.
AB - Background: The stress of complex medical course, emotional immaturity, and
adaptations to new surroundings are the challenges faced by the new medical
entrants. Therefore, mentorship program was introduced to support them for their
academic and personal development. Aim and Objectives: The aim of this study is
to introduce and to assess the perception of mentors and mentees on mentorship
program. Materials and Methods: A mentorship program was designed for Bachelor of
Medicine and Bachelor of Surgery (MBBS) First Professional students. A 1-day
workshop was conducted to sensitize the faculty. Seventeen faculty members from
various departments volunteered to be mentors. After sensitization, 150 MBBS
First Professional students were divided among these faculty members by lottery
system. A regular visit of mentees was scheduled with the mentor. At the end of
mentorship program, the perception of mentors and mentees was taken using a
validated and semi-structured feedback questionnaire. A focus group discussion of
students was also conducted. Results: A total of 112 students and 16 faculty
members completed the feedback questionnaire. The mentors considered this program
helpful in their self-improvement, teaching, and communication skills. Most of
the mentees felt that this program helped them emotionally and academically. It
was a good way to develop a strong student-teacher relationship. All the mentors
and mentees were satisfied with the mentorship program. Conclusions: The newly
introduced mentorship program helped in the overall development of mentors and
mentees. Both mentors and mentees were extremely satisfied with this program and
considered this as a successful intervention.
PMID- 29344463
TI - Team-based Learning Strategy in Biochemistry: Perceptions and Attitudes of
Faculty and 1st-Year Medical Students.
AB - Background: Team-based learning (TBL) strategy has been widely adapted by medical
schools all over the world, but the reports regarding the perceptions and the
attitudes of faculty and undergraduate medical students towards TBL approach have
been conflicting. Aim: The study aimed to introduce TBL strategy in curriculum of
Biochemistry after evaluating its effectiveness through perceptions and attitudes
of faculty and 1st-year medical students. Materials and Methods: One hundred and
fifty students of first professional M.B.B.S and five faculty members
participated in the study. Their responses regarding perceptions and attitudes
towards TBL strategy were collected using structured questionnaires, focus group
discussions, and in-depth interviews. Data were analyzed using Wilcoxon signed
rank test, paired sample t-test, and Mann-Whitney U-test. Results: Majority of
the students expressed satisfaction with team approach and reported improvement
in the academic scores, learning styles, and development of problem-solving,
interpersonal, and professional skills. The faculty, however, recommended a
modified TBL approach to benefit all sections of the students for the overall
success of this intervention. Conclusion: TBL is an effective technique to enable
the students to master the core concepts and develop professional and critical
thinking skills; however, for the 1st-year medical students, a modified TBL
approach might be more appropriate for the effective outcomes.
PMID- 29344464
TI - Cannabinoids in the Treatment of Epilepsy: Hard Evidence at Last?
AB - The interest in cannabis-based products for the treatment of refractory epilepsy
has skyrocketed in recent years. Marijuana and other cannabis products with high
content in Delta(9) - tetrahydrocannabinol (THC), utilized primarily for
recreational purposes, are generally unsuitable for this indication, primarily
because THC is associated with many undesired effects. Compared with THC,
cannabidiol (CBD) shows a better defined anticonvulsant profile in animal models
and is largely devoid of adverse psychoactive effects and abuse liability. Over
the years, this has led to an increasing use of CBD-enriched extracts in seizure
disorders, particularly in children. Although improvement in seizure control and
other benefits on sleep and behavior have been often reported, interpretation of
the data is made difficult by the uncontrolled nature of these observations.
Evidence concerning the potential anti-seizure efficacy of cannabinoids reached a
turning point in the last 12 months, with the completion of three high-quality
placebo-controlled adjunctive-therapy trials of a purified CBD product in
patients with Dravet syndrome and Lennox-Gastaut syndrome. In these studies, CBD
was found to be superior to placebo in reducing the frequency of convulsive
(tonic-clonic, tonic, clonic, and atonic) seizures in patients with Dravet
syndrome, and the frequency of drop seizures in patients with Lennox-Gastaut
syndrome. For the first time, there is now class 1 evidence that adjunctive use
of CBD improves seizure control in patients with specific epilepsy syndromes.
Based on currently available information, however, it is unclear whether the
improved seizure control described in these trials was related to a direct action
of CBD, or was mediated by drug interactions with concomitant medications,
particularly a marked increased in plasma levels of N-desmethylclobazam, the
active metabolite of clobazam. Clarification of the relative contribution of CBD
to improved seizure outcome requires re-assessment of trial data for the subgroup
of patients not comedicated with clobazam, or the conduction of further studies
controlling for the confounding effect of this interaction.
PMID- 29344466
TI - Comparison of Autonomic Function before and after Surgical Intervention in
Patients with Temporal Lobe Epilepsy.
AB - Background and Purpose: Refractory temporal lobe epilepsy (TLE) is commonly
associated with imbalances in cardiovascular (CV) parasympathetic and sympathetic
functions, which are treated using TLE surgery. We investigated the effect of
hemispheric lateralization of seizure foci on autonomic CV functions before and
after TLE surgery. Methods: The study was conducted on patients with left TLE
(LTLE, n = 23) and right TLE (RTLE, n = 30) undergoing unilateral TLE surgery. To
assess the autonomic CV functions, changes in the heart rate (DeltaHR) and blood
pressure (BP) were measured using a standardized battery of autonomic reactivity
tests before surgery and at 3 and 6 months after surgery. Results: Before
surgery, DeltaHR and the expiration to inspiration ratio (E:I) during the deep
breathing test were higher in the LTLE group than in the RTLE group (both p <
0.001), but both outcomes were comparable between the groups at 3 and 6 months.
DeltaHR decreased at 3 and 6 months (p < 0.001 and 0.01, respectively) compared
with preoperative values. The E:I at 3 months in the LTLE group was lower (p =
0.04) than the preoperative values. Decrease in systolic BP during the head-up
tilt test was greater in the LTLE group than in the RTLE group (p = 0.002) before
surgery. The maximum increase in diastolic BP during the cold pressor test was
lower in the RTLE group at 6 months than that before surgery (p = 0.001) and in
the LTLE group (p = 0.002). Conclusions: We found that hemispheric lateralization
of seizure foci in the temporal lobe had a differential effect on autonomic CV
functions before surgery. Before surgery, parasympathetic reactivity was higher
in the LTLE group, and sympathetic reactivity was higher in the RTLE group. After
surgery, autonomic CV functions were comparable between the groups, suggesting
that TLE surgery stabilizes autonomic CV functions.
PMID- 29344465
TI - Grey and White Matter Alterations in Juvenile Myoclonic Epilepsy: A Comprehensive
Review.
AB - Juvenile myoclonic epilepsy (JME) has been classified as a syndrome of idiopathic
generalized epilepsy and is characterized by a strong genetic basis, age-specific
onset of seizures, specific types of seizures, generalized spike-wave discharges
on electroencephalography, and a lack of focal abnormality on magnetic resonance
imaging (MRI). Recently, a wide range of advanced neuroimaging techniques have
been utilized to elucidate the neuroanatomical substrates and pathophysiological
mechanisms underlying JME. Specifically, a number of quantitative MRI studies
have reported focal or regional abnormalities of the subcortical and cortical
grey matter, particularly the thalamus and frontal cortex, in JME patients. In
addition, diffusion tensor imaging studies have pointed to disrupted
microstructural integrity of the corpus callosum and multiple frontal white
matter tracts as well as thalamofrontal dysconnectivity in JME patients.
Converging evidence from neuroimaging studies strongly suggests that JME is a
predominantly thalamofrontal network epilepsy, challenging the traditional
concept of JME as a generalized epilepsy. There is also limited evidence
indicating extrafrontal and extrathalamic involvement in JME. This systematic
review outlines the main findings from currently available MRI studies focusing
on grey and white matter alterations, and discusses their contributions to the
etiology and pathophysiology of JME. The clinical utility, advantages, and
drawbacks of each imaging modality are briefly described as well.
PMID- 29344467
TI - Longitudinal Change in Thyroid Hormone Levels in Children with Epilepsy on a
Ketogenic Diet: Prevalence and Risk Factors.
AB - Background and Purpose: The aim of this study is to evaluate the prevalence of
hypothyroidism and the change of thyroid hormone level in the children with
epilepsy on a ketogenic diet (KD). Methods: The levels of serum free thyroxine
(fT4) and thyroid-stimulation hormone (TSH) were measured at the start of the KD
and at 6- to 12-month intervals in children with intractable epilepsy.
Hypothyroidism was defined as fT4 level < 0.8 ng/dL and TSH level > 6.0 MUIU/mL.
Results: A total of 28 children (17 boys and 11 girls) were enrolled in the
study. The mean age of onset of seizure was 1.4 +/- 1.6 years, the mean age of
the start of the KD was 3.2 +/- 2.4 years, and the mean duration of KD was 1.9 +/
1.5 years. Overall, there was no significant longitudinal change in the mean fT4
(0.99 +/- 0.25 vs. 0.94 +/- 0.71 ng/dL, p = 0.28) and TSH (2.94 +/- 1.32 vs. 3.18
+/- 1.21 MUIU/mL, p = 0.44) levels from the start of the KD to last follow-up.
The patients with a younger age of seizure onset, earlier initiation of KD, and
higher serum levels of cholesterol and triglyceride had a significant decrease in
fT4 levels and increase in TSH levels during the KD. Sex, duration of the seizure
or KD therapy, seizure types, seizure frequency, seizure outcomes, brain lesion,
ratio of KD, and being overweight did not affect the longitudinal change of fT4
and TSH levels during KD. Conclusion: Thyroid function had no significant
longitudinal decrease in pediatric epilepsy during KD therapy. However, careful
monitoring of the serum levels of fT4/TSH should be recommended in children on
KDs, especially in those with earlier seizure onset, earlier start of KD, and
higher levels of lipid profiles.
PMID- 29344468
TI - Levetiracetam-Induced Skin Hyperpigmentation: An Extremely Rare Undesirable Side
Effect.
AB - Levetiracetam is one of the newer second-generation antiepileptic drugs with
multiple mechanisms of action. Cutaneous side effects due to levetiracetam are
rarely reported in the literature. In this article, we describe a patient with
skin hyperpigmentation due to the treatment with levetiracetam with complete
resolution after discontinuation of the medication. In addition, we review the
topic and hypothesize the mechanism behind this rare complication. To the best of
our knowledge, this is the first report of skin hyperpigmentation as a side
effect of levetiracetam in the literature. The prescribing physicians should
inform the patients about all potential side effect of levetiracetam including
skin hyperpigmentation. Similar to many undiagnosed conditions, increased
awareness of their existence is the key to diagnosis. Early recognition and
timely cessation of therapy are important to reverse this effect. Further studies
should be conducted to explore the pathophysiology of this rare side effect.
PMID- 29344469
TI - Successful Use of Therapeutic Hypothermia for Refractory Nonconvulsive Status
Epilepticus.
AB - Therapeutic hypothermia (TH) has rarely been utilized as an adjunct to
anticonvulsants in treating patients with refractory convulsive status
epilepticus (CSE). However, determining the effectiveness of TH in CSE is
difficult due to the unavoidable use of sedative drugs to manage hypothermia.
Additionally, the effectiveness of TH has not been studied in patients with
refractory non-convulsive status epilepticus (NCSE). Here, we report the
successful use of TH without additional sedative drugs in a patient with temporal
lobe epilepsy and refractory NCSE. A 46-year-old man was referred to the
neurology department because of recurrent seizure attacks. Electroencephalography
(EEG) after first-line status treatment showed continuous periodic discharges
consistent with NCSE. He was started simultaneously on continuous EEG monitoring
and TH, but was not administered any benzodiazepines to control shivering or
maintain TH. During TH, EEG abnormalities gradually improved, and the patient
regained consciousness in accordance with the improvement in EEG. The patient was
alert and his EEG had normalized a few days after starting TH. To the best of our
knowledge, this is the first report describing the successful treatment of
refractory NCSE with TH. As no sedative drugs were used during the maintenance of
hypothermia, NCSE control may have been achieved by TH alone.
PMID- 29344470
TI - Aphasic Status Epilepticus Associated with Uremia.
AB - Aphasic status epilepticus (ASE) is a rare disorder characterized by recurrent
aphasia without impairment of other cognitive functions. A 76-year-old woman with
chronic kidney disease developed ASE after neglecting peritoneal dialysis.
Magnetic resonance imaging failed to demonstrate an appropriate lesion.
Electroencephalography demonstrated ictal discharges in the left frontotemporal
leads. ASE disappeared after intravenous valproic acid and correction of uremia.
This is the first case report of ASE in a patient with acute aggravation of
uremia.
PMID- 29344471
TI - A 6-Month-Old Girl with Incontinentia Pigmenti Presenting as Status Epilepticus.
AB - Incontinentia pigmenti (IP) is an uncommon neurocutaneous syndrome. Its initial
diagnosis is based primarily on characteristic papulovesicular skin lesions and
early-onset neonatal seizures. In contrast to typical early neurologic
manifestations, we encountered a normally developed 6-month-old female patient
with hyperpigmented whorls on her body. Following respiratory syncytial virus
infection and fever, the patient exhibited status epilepticus. Brain magnetic
resonance imaging studies of the patient were compatible with the findings of
acute encephalopathy in IP. Genetic analysis showed an 11.7 kb deletion within
the gene encoding inhibitor of kappa-B kinase gamma. The patient was treated with
anticonvulsants and subsequently reached expected developmental milestones after
discharge. These findings indicate that when a patient presents with status
epilepticus, meticulous examination for skin lesions should be performed to
determine whether the patient has a neurocutaneous syndrome, such as IP.
PMID- 29344472
TI - Status Epilepticus as an Unusual Manifestation of Heat Stroke.
AB - Heat stroke (HS) is a medical emergency and life threatening condition,
characterized by body temperature over 40 degrees C. This can lead to dysfunction
of multiple organs such as the heart, liver, kidneys, lungs, blood coagulation
system, and central nervous system. Neurological complications include change in
consciousness, cerebellar dysfunction, convulsions, aphasia, muscular weakness,
and parkinsonism. Cerebellar syndrome is the most common neurological finding in
HS. We report a case of HS presenting with status epilepticus, without any other
neurological manifestations. A 42 year old man, previously diagnosed with bipolar
disorder, was admitted to the emergency room with high fever and repetitive
generalized tonic-clonic seizures. He had been found unconscious after 4 hours of
heavy physical work under extremely hot weather conditions. He was diagnosed with
HS accompanied by status epilepticus, and treated with emergency body cooling and
antiepileptics. Five days after admission, he regained consciousness and the
laboratory parameters that were initially abnormal returned to normal values. On
day 14, he was discharged without any neurological complications.
PMID- 29344473
TI - Intractable Epilepsy with Solitary Cerebral Calcification.
AB - Cerebral calcification is a common incidental finding upon brain imaging and its
epileptogenicity is often underestimated. Here, we report a case of intractable
epilepsy arising in conjunction with a solitary cerebral calcification. A 42-year
old male with intractable epilepsy was admitted to the epilepsy clinic for
invasive epilepsy surgery. Brain magnetic resonance imaging revealed a slight
high-intensity signal change in the right amygdala and a small, calcified lesion
in the right lateral temporal region. The patient underwent invasive monitoring
with subdural electrodes. He had five habitual seizures with automatisms and fast
activity. These seizures initiated in the right lateral temporal area just above
the solitary calcified lesion. Neuropathology of the calcified lesion showed no
specific findings apart from a fibrocalcific nodule. Thus, although solitary
cerebral calcifications may be an asymptomatic or coincidental finding in some
patients, they may also have a highly epileptogenic focus.
PMID- 29344474
TI - Corneal Myofibroma (Keloid) in a Young Patient with Neurofibromatosis Type 2.
AB - We present a 27-year-old male patient with neurofibromatosis type 2 (NF2), facial
palsy, and lagophthalmos following acoustic neuroma removal and an impressing
vascularized corneal tumor, which was excised. Histology showed a fibrous tumor
with small vessels, and immunohistochemistry was positive for vimentin and
negative for smooth muscle actin, S100, and GFAP. We assume a corneal myofibroma
(keloid), which in this case rather represents a reactive lesion. This entity has
not been described before in NF2 or in facial palsy-associated lagophthalmos in
general.
PMID- 29344475
TI - Ring-Shaped Leiomyoma of the Ciliary Body.
AB - Purpose: Ciliary body mesectodermal leiomyoma is a rare, benign smooth muscle
tumor that typically presents in women in the second to fourth decade of life.
The diagnosis is typically based on clinical color, funduscopic appearance,
transillumination properties, and B-scan ultrasonography. Methods: We present a
patient with a 360 degrees ciliary body mass with transillumination and
ultrasonographic properties consistent with a ring melanoma. Results: This case
emphasizes the difficulty in differentiating the benign leiomyoma from similar
appearing malignant tumors such as melanoma. Conclusion: The eye was enucleated
and the diagnosis was ring-shaped leiomyoma.
PMID- 29344476
TI - Acute Angle Closure Precipitated by Hemorrhage and Necrosis of a Large Uveal
Melanoma in the Setting of Systemic Immunomodulatory Therapy.
AB - Management of nonmetastatic uveal melanoma has been well studied and a large body
of work has been published by the Collaborative Ocular Melanoma Study (amongst
many others). Management of uveal melanoma that is found to be metastatic upon
initial diagnosis, however, is less well defined. We report an interesting case
of acute angle closure caused by necrosis and hemorrhage into a large uveal
melanoma occurring shortly after initiation of immunomodulatory therapy with
ipilimumab and nivolumab for metastatic disease. The use of these
immunomodulatory agents in the setting of metastatic uveal melanoma is not well
studied, and our case illustrates the importance of interdisciplinary
communication in order to best decide the timing of surgical and systemic medical
management to optimize outcomes and minimize morbidity.
PMID- 29344477
TI - Is There an Increased Prevalence of Asteroid Hyalosis in Eyes with Uveal
Melanoma? A Histopathologic Study.
AB - During the planning meeting for the Collaborative Ocular Melanoma Study (COMS)
prior to the start of patient recruitment in 1986, there was an interest
expressed in determining whether a relationship existed between the presence of
uveal melanoma (UM) and asteroid hyalosis (AH). To answer this question, the
ophthalmic examination form (unlike the pathology form for enucleated eyes) for
each COMS patient asked whether AH was present or not. Though an increased
prevalence was not found, this result was never published. A recent unpublished
study at the University of Wisconsin School of Veterinary Medicine indicated a
higher prevalence of AH in canine eyes with UM when compared to control eyes
(without tumor) enucleated for goniodysgenesis. This further increased our
interest in revisiting the published literature, clinical records, and
histopathology slides of the enucleated eyes from the COMS study, as well as the
histopathology slides on file in the University of Wisconsin Eye Pathology
Laboratory. While cases with both AH and UM were occasionally encountered in the
literature, clinically, we could not find a previous study focusing on these two
processes. This study was conducted to explore whether such an association
exists.
PMID- 29344478
TI - Incidentally Discovered Adenoid Cystic Carcinoma of the Lacrimal Gland with
Isolated Liver Metastases.
AB - Aim: To report a rare presentation of adenoid cystic carcinoma (ACC) of the
lacrimal gland. Method: This is a case report presenting clinical, radiographic,
and histopathologic findings. Results: A 72-year-old female with no reported
ocular symptoms was found to have an incidental right orbital mass on imaging.
Additional studies revealed multiple liver lesions, which were biopsied and found
to be consistent with ACC. She was then referred to the ophthalmology service,
where ocular examination demonstrated 2.5 mm of right proptosis with elevation
and abduction deficits. Diplopia could be elicited in extreme upgaze and right
lateral gaze. An excisional biopsy of the orbital mass was performed, with
histopathology confirming the diagnosis of primary ACC of the lacrimal gland,
thereby also supporting the initial suspicion that the hepatic ACC lesions
represented metastases. Conclusion: The authors describe a rare presentation of
ACC of the lacrimal gland, initially asymptomatic, with metastatic lesions
restricted to the liver at the time of diagnosis. Three previous cases of ACC
with isolated metastatic hepatic lesions at the time of diagnosis have been
reported; all of these cases localized the primary tumor to the salivary glands.
PMID- 29344479
TI - Mechanisms of Optic Nerve Invasion in Primary Choroidal Melanoma.
AB - Aim: The aim of this study was to assess morphological risk factors associated
with optic nerve invasion of choroidal melanoma and to identify possible
mechanisms of optic nerve invasion. Methods: Medical charts and histology slides
of patients with primary choroidal melanoma who were treated by
enucleation/exenteration and whose pathology showed optic nerve invasion were
reviewed. Results: Twenty-one patients (mean age: 65.67 +/- 14.72 years) with
primary uveal melanoma arising from the choroid were included in this analysis. A
peripapillary location was present in 86% of the cases. Four types of optic nerve
invasion were identified: transvitreal invasion (10%); retinal invasion (23%);
direct peripapillary invasion (57%); and a combined mechanism (10%). Optic nerve
invasion was prelaminar in 67%, laminar in 10%, and retrolaminar in 23% of the
cases. Significantly higher largest basal diameter (p = 0.021) and tumor
thickness values (p = 0.017) and higher rates of vortex vein (p = 0.022) and
retinal invasion (p = 0.007) were observed in the transvitreal/retinal invasion
groups when compared to the direct peripapillary invasion group. Conclusions: A
peripapillary tumor location was the most common mechanism of optic nerve
invasion of choroidal melanoma. In 43% of the cases, other mechanisms including
transvitreal and retinal invasion resulted in optic nerve invasion.
PMID- 29344480
TI - Primary Conjunctival Tuberculosis Presenting as Dry Eye: A Rare Case Report and
Review of the Literature.
AB - Primary conjunctival tuberculosis is very rare in the developed countries. In an
endemic country like India, it should be considered in the differential diagnosis
of any unusual conjunctival lesion with unilaterality, chronicity, and
nonresolution of symptoms after steroid use. We present the case of a 52-year-old
female who presented with unilateral itching and blurring of vision for 20 days.
There were irregular nodular elevated areas with shrinkage of the lower palpebral
conjunctiva. A biopsy of the lesion revealed necrotizing epithelioid cell
granulomas along with Langhans type of giant cells. However, no acid-fast bacilli
were seen on Ziehl-Neelsen stain. Systemic examination of the patient was normal,
and there was no evidence of pulmonary tuberculosis. Polymerase chain reaction of
conjunctival scrapings was positive for Mycobacterium tuberculosis. The patient
was started on antitubercular drugs. We present this very rare case of primary
tuberculosis of the conjunctiva presenting with dryness of the eye.
PMID- 29344481
TI - Choroidal Melanoma Mimicker: A Case of Metastatic Clear-Cell Renal Cell
Carcinoma.
AB - Choroidal melanoma is the most common primary intraocular malignancy, yet
metastatic disease remains the most common malignancy of the eye. Differentiating
these entities is essential as treatment, systemic associations, and prognosis
vary dramatically between the two. Established diagnostic criteria are accurate
for the diagnosis of uveal melanoma. Yet, metastatic disease may be misdiagnosed
as a uveal melanoma in rare cases. We report a case of metastatic clear-cell
renal cell carcinoma masquerading as uveal melanoma. A 73-year-old Caucasian man
with a history of renal cell carcinoma presented with a 15 * 12 * 7 mm
homogenous, pigmented, and acoustically hollow mass without hemorrhage or
exudation. The patient was initially treated with plaque radiotherapy with good
tumor regression. However, the patient developed pain and vision loss due to
total exudative retinal detachment. Subsequent enucleation allowed
histopathologic confirmation of clear-cell renal cell carcinoma. Nine years
following enucleation, the patient remains in complete remission without evidence
of other systemic metastases. Renal cell carcinoma should be considered when
evaluating patients with probable uveal melanoma. Delayed-onset ocular metastasis
from renal cell carcinoma exhibits an atypical clinical course with the
possibility of durable remission following enucleation.
PMID- 29344482
TI - Optic Nerve Obscuration in Retinoblastoma: A Risk Factor for Optic Nerve
Invasion?
AB - Background: The objective of this study is to evaluate the risk of optic nerve
invasion associated with optic nerve obscuration at diagnosis or persisting
during treatment. Methods: Retrospective review from 2011-2016 of patients with
advanced retinoblastoma (Group D/E) with complete obscuration of the nerve at
diagnosis and a second group of patients with persistent, complete obscuration
throughout treatment. Results: Advanced retinoblastoma was diagnosed in 102 eyes
of 86 patients. The optic nerve was obscured in 69 eyes (68%) at diagnosis. Of
these, 30 (43%) underwent salvage therapy and 39 (57%) primary enucleation.
Histopathologic analysis of primarily enucleated eyes showed 41% prelaminar and
15% postlaminar invasion. Four eyes in the salvage group demonstrated persistent
nerve obscuration; 2 were subsequently enucleated without evidence of nerve
invasion. Average follow-up was 23.5 months (range 1-62 months). Conclusions and
Relevance: Optic nerve obscuration at diagnosis may be associated with
postlaminar optic nerve invasion. While persistent, complete obscuration of the
optic nerve by retinoblastoma during treatment is a poor prognostic sign for both
globe salvage and vision, it does not appear, in this small cohort, to increase
the risk of optic nerve invasion. With appropriate control of the intraocular
tumor, these eyes can be salvaged.
PMID- 29344483
TI - Retinoinvasive Uveal Melanoma: Report of 2 Cases and Review of the Literature.
AB - Purpose: To describe the clinical history and histopathologic findings of 2 cases
of retinoinvasive uveal melanoma. Methods: The medical records and pathology
specimens of 2 patients with retinoinvasive uveal melanoma were reviewed.
Results: The first patient had an iris/ciliary body melanoma that was treated and
the second patient had suspected iridocorneal endothelial syndrome. Both patients
developed a blind, painful eye; the first patient's right eye was enucleated and
the left eye of the second patient underwent evisceration. Histopathologic
examination of the enucleated eye showed a tumor composed of minimally pigmented
spindle-shaped cells with fusiform nuclei and prominent nucleoli and round cells
with prominent nucleoli. The tumor cells invaded into the retina where they
formed perivascular aggregates. Examination of the evisceration specimen showed a
proliferation of pigmented tumor cells within the stroma of one iris leaflet. The
tumor cells extended onto the ciliary body and vitreous base and invaded the
retina. The pathologic diagnosis in both patients was retinoinvasive uveal
melanoma. Conclusions: Careful funduscopic and imaging examination should be
performed in eyes with unilateral glaucoma with iris/ciliary body lesions, and
enucleation, rather than evisceration, should be performed, as retinoinvasive
melanoma is in the differential diagnosis.
PMID- 29344484
TI - Adenocarcinoma of the Retinal Pigment Epithelium Arising in Conjunction with Late
Recurrence and Systemic Metastasis of Retinoblastoma.
AB - In 1974, an 8-month-old male was diagnosed with bilateral retinoblastoma. His
left eye was enucleated, while the right eye was salvaged with a combination of
external beam radiotherapy (4,000 cGy total, divided in 20 fractions) and retinal
laser treatment. Thirty-nine years later, he developed intraocular recurrence of
retinoblastoma with extrascleral spread. Histopathological examination also
identified a second distinct malignancy, retinal pigment epithelium
adenocarcinoma, arising in continuity with the retinoblastoma. Further
investigation revealed foci of metastatic retinoblastoma in his parotid gland. He
was subsequently treated with a combination of orbital exenteration, extensive
neck dissection, and resection of metastatic foci, followed by a high-dose
ablative chemotherapeutic regimen consisting of cisplatin, vincristine, and
cyclophosphamide. Although very rare, late recurrence of retinoblastoma with
systemic metastasis is possible, and continued clinical observation and
appropriate long-term follow-up should be considered. Additionally, it is
important to consider a second primary intraocular tumor in the differential
diagnosis, especially in a patient with heritable retinoblastoma who has
undergone radiation therapy.
PMID- 29344485
TI - Prognostication for Uveal Melanoma: Are Two Tests Better than One?
PMID- 29344486
TI - Acute Presentation of Mesectodermal Leiomyoma of the Ciliary Body.
AB - Purpose: We report a case of acutely presenting mesectodermal leiomyoma of the
ciliary body in a 29-year-old female who reported waking up with swollen eyelids
of the right eye and light-perception vision. The affected eye had elevated
intraocular pressure, a flat anterior chamber, and a pale, round mass arising
from the nasal ciliary body, invading the angle and protruding into the visual
axis posterior to the lens. Within days, the visual acuity decreased to no light
perception. The eye was enucleated. Methods: The enucleated eye harbored a tumor
arising from the ciliary body, measuring 18 mm in the greatest dimension.
Spindled cells with fibrillary cytoplasmic processes suggested a neural origin
though negative for S-100, Melan-A, and HMB-45. The cells stained strongly
positive for smooth muscle actin and vimentin, leading to the diagnosis of
mesectodermal leiomyoma of the ciliary body. Results: We review the literature to
expand upon the clinical findings, diagnostic methods, and histopathologic and
immunohistochemistry characteristics of mesectodermal leiomyoma. Conclusion:
Leiomyoma must be in the differential diagnosis for ciliary body mass, especially
in women of reproductive age. Diagnosis relies on histopathology and
immunohistochemistry. The mechanism of acute symptom onset may be multifactorial.
This case emphasizes the possibility of acute presentation of a rare, benign
intraocular tumor.
PMID- 29344487
TI - Enlarging Pigmented Eyelid Mass Associated with Remote Pencil Trauma.
AB - The authors present a case of a gradually enlarging pigmented mass of the upper
eyelid and anterior orbit that was discovered to be the graphite tip of a pencil
surrounded by macrophages bearing graphite and fibrous tissue. A 25-year-old
woman with no medical history presented with a gradually enlarging pigmented
lesion of her left upper eyelid. She denied any history of previous skin cancer,
trauma, or previous surgery. A biopsy was performed. This revealed an
encapsulated grayish, pigmented mass within the medial portion of the left upper
eyelid and anterior orbit. Within the pigmented cocoon, the graphite core of a
pencil ("pencil lead") was identified. Histopathology demonstrated granulomatous
inflammation with fibrosis and macrophages.
PMID- 29344488
TI - Intravitreal Aflibercept as Rescue Therapy for Post-Radiation Cystoid Macular
Edema Resistant to Intravitreal Bevacizumab: Outcomes at 1 Year.
AB - Background/Aims: To investigate the efficacy of intravitreal aflibercept as
rescue therapy for post-radiation cystoid macular edema (CME) resistant to prior
treatment with intravitreal bevacizumab (IVB). Methods: Retrospective,
interventional, case-controlled series. Eyes with persistent post-radiation CME
were treated with intravitreal aflibercept (2 mg/0.05 mL). Central macular
thickness (CMT) and visual acuity were compared to a matched control group
treated with only IVB at 1 year. Results: Ten eyes of 10 patients were included,
with 5 eyes in the intervention and 5 in the control group. The eyes in the
intervention group had previously been treated with IVB (mean 11.6 injections,
range 6-22) but failed to show resolution of CME. Following rescue treatment with
a mean of 9 injections of aflibercept, the mean CMT was reduced from 463 +/- 138
to 267 +/- 80 MUm (p = 0.02) and the mean Snellen visual acuity was improved from
20/67 to 20/42 (p = 0.03). At 1 year, the eyes in the intervention group had
lower CMT (267 +/- 80 vs. 361 +/- 71 MUm, p = 0.09) and significantly better
Snellen visual acuity (20/48 vs. 20/76, p = 0.02) compared to the control group.
Conclusions: Aflibercept may be an effective rescue therapy for persistent post
radiation CME in eyes with incomplete response to IVB, with reduction in CMT and
improvement in visual acuity.
PMID- 29344489
TI - Caruncular Oncocytoma Mimicking Malignant Melanoma.
AB - Purpose: To report a case of pigmented caruncular oncocytoma that simulated
malignant melanoma and discuss the associated ultrasonographic and pathologic
features. Method: Case report. Results: An 81-year-old female presented with a
painless caruncular mass with a smooth brown surface suspicious for melanoma.
Ultrasound biomicroscopy revealed a round mass with a large central cavity, more
suggestive of a cystic rather than solid lesion. Following complete surgical
resection, histopathology revealed a cystadenomatous lesion composed of bland
cells with copious eosinophilic cytoplasm consistent with oncocytoma that had a
central blood-filled cavity. Conclusions: Oncocytoma is a benign tumor that can
appear pigmented clinically and resemble melanoma. The definitive diagnosis
requires histopathologic evaluation. Oncocytoma should be considered in the
differential diagnosis of a pigmented caruncular mass.
PMID- 29344490
TI - Capillary Dropout: A Novel Fluorescein Angiography Finding in Primary
Vitreoretinal Lymphoma.
AB - Tissue diagnosis with vitreous and/or retinal biopsy usually confirms the
diagnosis of primary vitreoretinal lymphoma. Multiple imaging modalities like
fundus fluorescein angiography, fundus autofluorescence, and optical coherence
tomography have been used to support the diagnosis of vitreoretinal lymphoma. We
report a case of a 74-year-old lady diagnosed with primary vitreoretinal lymphoma
showing a novel fluorescein angiographic finding of capillary dropout. We
hypothesize that this clinical finding on the fluorescein angiogram may be due to
the occlusion of the retinal vasculature by the malignant tumor cells. This
finding also suggests the possible intraocular invasion of the malignant
lymphomatous cells into the inner retinal layers.
PMID- 29344491
TI - Hemophagocytic Lymphohistiocytosis in Adults with Intraocular Involvement:
Clinicopathologic Features of 3 Cases.
AB - Background/Aims: Hemophagocytic lymphohistiocytosis (HLH) is an infrequent
inflammatory multisystemic syndrome. Only rare cases with ophthalmic involvement
describing their pathologic features have been previously reported. Methods: We
report 3 cases of adult-onset HLH with bilateral ocular involvement and describe
their clinicopathologic features. Results: Three adult males - 2 with a history
of viral infection - developed persistent fever, fatigue, bone marrow
abnormalities, and irreversible multiorgan failure. Visual impairment was also
documented in 2 cases. Complete autopsies were performed. Ophthalmic pathology
demonstrated a bilateral histiocytic infiltrate with scant lymphocytes affecting
the uvea. Focal extension to the retina, optic nerve, and trabecular meshwork
were also identified, as well as hemophagocytosis in 1 case. Macrophages showed
strong immunoreactivity for CD163 antibody and lacked BRAF p.V600E mutant
protein. Conclusion: HLH is an unusual disorder associated with several systemic
conditions. Histologic features in the eye are poorly documented, with prior
reports restricted to children. Our 3 adult cases are reported using updated
criteria and, despite the difference in age, show changes similar to those
observed in the pediatric population.
PMID- 29344492
TI - Bilateral Hypopyon Uveitis in Chronic Myeloid Leukemia.
AB - Background: A leukemic hypopyon is considered an early sign of central nervous
system involvement or systemic relapse. A differential diagnosis of masquerade
syndromes should be considered in cases of hypopyon uveitis that are atypical or
unresponsive to treatment. We report a case of a 45-year-old man who presented
with bilateral hypopyon uveitis and was subsequently diagnosed as having chronic
myeloid leukemia. Method: Retrospective case review. Results: A 45-year-old
diabetic male presented with diminished vision in both eyes for 10 days.
Ophthalmic evaluation revealed rubeosis iridis, hypopyon, and signs of
proliferative diabetic retinopathy with panretinal laser photocoagulation scars.
He subsequently presented 1 week later with a bloodstained hypopyon in his right
eye and a persistent hypopyon in his left eye. A peripheral blood smear and
subsequent bone marrow trephine biopsy confirmed the diagnosis of chronic myeloid
leukemia in blast crisis and he was referred to an oncologist for further
management. Conclusion: A recalcitrant or atypical hypopyon uveitis can be an
indicator of a blast crisis or a central nervous system involvement or sign of a
relapse in cases of leukemia. The presence of unusual bloodstained hypopyon
helped in identifying the presence of chronic myeloid leukemia and aided in a
prompt oncology consultation.
PMID- 29344494
TI - Inhomogeneous Surface Dose Distributions of 106Ru Eye Plaques.
PMID- 29344493
TI - Comparison of Gene Expression Profiling and Chromosome 3 Analysis by Fluorescent
in situ Hybridization and Multiplex Ligation Probe Amplification in Fine-Needle
Aspiration Biopsy Specimens of Uveal Melanoma.
AB - Purpose: The aim of this paper was to assess the concordance between results of
DecisionDx-UM specific gene expression profiling (GEP) and fluorescence in situ
hybridization (FISH) for chromosome 3 analysis, and between DecisionDx-UM GEP and
multiplex ligation probe amplification (MLPA) in uveal melanoma undergoing
intraoperative fine-needle aspiration biopsy (FNAB) for metastatic
prognostication during brachytherapy. Methods: We retrospectively reviewed
consecutive patients diagnosed with posterior uveal melanoma who underwent
intraoperative FNAB prior to placement of an iodine-125 radioactive plaque
between 2012 and 2014. Two cohorts of patients were identified: Cohort 1 - tumors
in which both GEP and FISH results were obtained, and Cohort 2 - tumors in which
both GEP and MLPA results were obtained. Results: Forty-four patients were
identified for Cohort 1. FISH and GEP results were discordant in 7 tumors
(15.9%). Forty-three patients were identified for Cohort 2. MLPA and GEP were
discordant in 7 tumors (16.3%). Conclusions: Discordance between GEP and
chromosome 3 status by FISH and MLPA occurred in our series at a rate of 15.9 and
16.3%, respectively. Caution must be advised when counseling a patient with a
good-prognosis GEP "Class 1" result that the uveal tumor may actually harbor
monosomy 3, which is associated with a poor prognosis for metastasis in nearly
20% of the patients.
PMID- 29344495
TI - Retinoblastoma: A Sixteen-Year Review of the Presentation, Treatment, and Outcome
from a Tertiary Care Institute in Northern India.
AB - Purpose: To study epidemiology, demographic profile, clinical characteristics,
and outcome in pediatric patients with retinoblastoma. Methods: This was a
retrospective review of retinoblastoma patients of a tertiary institute from
January 1st 1998 to December 31st 2014. Results: The study included 467 patients
(618 eyes) with a mean age of 34.7 +/- 24.6 months (median = 30; 15 days to 144
months). Retinoblastoma was bilateral in 151 (32.3%) and there were 61.7% males.
Intraocular disease was seen in 301 patients (451 eyes [72.9%]) and extraocular
in 166 patients (167 eyes; 27.0%). Out of the 347 (74.3%) who received treatment,
primary treatment was chemoreduction in 228 (65.7%) and enucleation in 117
(33.7%), while 25.6% of patients refused treatment and 151 (43.5%) defaulted
therapy. Local recurrence was seen in 20 (4.3%), metastasis in 2 (0.4%), and
deaths in 13 (2.8%) (average follow-up 28.5 +/- 44.4 months). Histopathological
high risk features were significantly less in the eyes that received
chemoreduction (5.0%) versus primary enucleation (20.8%) (p < 0.0004), but there
was no difference in the rate of metastasis, recurrence, and death between the
two. Conclusions: The majority of retinoblastoma patients in our study had
advanced disease, and nearly a third had extraocular extension. There were a
significant number of therapy refusals and dropouts. Chemoreduction led to a
significant decrease in the histopathological risk factors without affecting the
outcomes.
PMID- 29344496
TI - Quadruple Neoplasms following Radiation Therapy for Congenital Bilateral
Retinoblastoma.
AB - Purpose: The aim of this study was to describe a 34-year-old male with hereditary
bilateral retinoblastoma treated with radiotherapy as a child who developed 4
distinct tumors within the radiation field. Methods: A 34-year-old male with
bilateral retinoblastoma status postradiation therapy and recurrence requiring
enucleation presented with left-eye visual acuity changes. Magnetic resonance
imaging demonstrated a left orbital mass and a right parasellar complex lobulated
mass (right sphenoid and right cavernous sinus). Two weeks later, the patient
underwent excision of the orbital mass and biopsy of an upper-lid nodule. This
was followed by craniotomy for removal of the complex mass. Results: Histology
revealed 4 distinct tumors, including an undifferentiated pleomorphic sarcoma
(left orbit), a radiation-induced meningioma (right sphenoid), a schwannoma
(right cavernous sinus), and a basal-cell carcinoma (left lid). Conclusion:
Although occurrence of a second neoplasm is a well-known outcome following
radiation treatment in patients with hereditary retinoblastoma, the diagnosis of
4 additional neoplasms is rare. Pleomorphic sarcoma, radiation-induced
meningioma, and schwannoma are uncommon tumors and not well represented in the
literature describing irradiated retinoblastoma patients. Secondary malignancies
are a leading cause of early death in retinoblastoma survivors, and long-term
follow-up is crucial for patient care.
PMID- 29344497
TI - A Case of Adenocarcinoma of the Retinal Pigment Epithelium: An
Immunohistochemical and Electron Microscopic Study.
AB - Purpose: Retinal pigment epithelium (RPE) adenocarcinoma is a very rare malignant
intraocular tumor. Herein we describe the histopathological features of RPE
adenocarcinoma. Case: A 36-year-old male was referred to our clinic because of
floaters in his left eye. The initial diagnosis was malignant melanoma of the
choroid. We resected the tumor and studied it histopathologically. The tumor
tissue was investigated by light microscopy including immunohistochemistry using
antibodies against S-100, HMB-45, EMA, and AE-1. Electron microscopic examination
was also performed. Results: The tumor arose from the RPE and contained
intracytoplasmic vacuoles and abundant melanin pigment. There were no nevoid
cells in the choroid. A small part of the tumor cells showed tubular or lobular
proliferation and choroidal invasion. Immunohistochemistry revealed positive
staining in tumor cells with 4 antibodies. Tight cellular junctions specific to
the RPE were confirmed by electron microscopy. The final diagnosis was RPE
adenocarcinoma. Conclusions: Most pigmented intraocular tumors are nevus and
malignant melanomas of the choroid. It is easy to misdiagnose a RPE
adenocarcinoma as a malignant melanoma of the choroid. An exact differential
diagnosis should be determined by immunohistopathological and electron
microscopic examination.
PMID- 29344498
TI - Selective Intra-Arterial Embolization for Advanced Extrascleral Uveal Melanoma.
AB - Purpose: To report a treatment approach for advanced extrascleral uveal melanoma.
Methods: We performed clinical examination including magnetic resonance imaging,
computed tomography, angiography, and histopathologic analysis. Case: A 49-year
old healthy woman presented with a 7-year history of an enlarging pigmented mass
in her right orbit. Malignant melanoma was diagnosed after biopsy with
immunohistochemical stains. Treatment included selective intra-arterial
embolization. Results: A significant reduction in tumor burden was seen 3 months
after intra-arterial embolization. No complications were associated with the
treatment. Conclusion: Selective intra-arterial embolization may allow adequate
palliative therapy in select cases of advanced extrascleral uveal melanoma.
PMID- 29344499
TI - Unilateral Multifocal Choroidal Melanoma.
AB - We report a case of multifocal choroidal melanoma in the same eye, separated in
presentation by 20 years. A 57-year-old Caucasian male initially presented with a
choroidal melanoma of the right eye that was treated with transpupillary
thermotherapy. Due to recurrence, the patient underwent proton beam therapy with
subsequent tumor regression. A second small choroidal lesion was noted in the
right eye during his surveillance examinations that was closely monitored and
demonstrated stable dimensions and features suggestive of a choroidal nevus.
Twenty years after his first presentation, the second lesion exhibited
accelerated growth with imaging studies indicative of transformation to a
distinct choroidal melanoma. The patient underwent a second globe salvage
treatment of proton beam therapy. We describe the clinical course, radiographic,
and imaging findings of this rare choroidal melanoma.
PMID- 29344500
TI - Pilot Study of a "Large-Eye," Surgically Induced Dry Eye Rabbit Model by
Selective Removal of the Harderian, Lacrimal, and Meibomian Glands.
AB - Background/Aims: Establish a reliable rabbit dry eye (DE) model. Methods: An
interventional cohort study surgically removing glands contributing to the tear
film. Eight rabbits were studied after removal of left lacrimal, Harderian, or
both glands. Additional rabbits had Meibomian glands in the left eye thermally
obstructed. All were followed for 10 weeks with phenol red thread (PRT) and slit
lamp examination with 2% fluorescein. We assessed corneal sensitivity using a
Cochet-Bonnet esthesiometer. Outcome measures were severity/duration of reduced
PRT, punctate epithelial erosions (PEE), and histologic evidence of corneal
pannus. Results: Fluorescein staining demonstrated signs of dryness including PEE
in all of the interventional eyes. The subjective measurement of epithelial
erosions correlated with decreased tear production. PRT measurements in the
control eyes averaged 31.54 mm (+/-1.83) and 22.71 mm (+/-1.60) in the eight left
eyes, without loss of corneal sensitivity. Conclusions: Surgical removal of
either the Harderian or lacrimal gland results in statistically significant
decreases in tear volume and the development of severe DE. Removal of both glands
results in the occurrence of a DE of comparable severity/duration to removal of
either the lacrimal or Harderian gland alone. Meibomian gland obstruction
contributes less to the DE model.
PMID- 29344501
TI - Pigmented Epithelioid Melanocytoma of the Cheek, Orbit, and Intracranial Cavity:
A Case Report.
AB - Pigmented epithelioid melanocytoma (PEM) of the skin has been rarely reported in
ophthalmology. The purpose of this case report is to present a young male born
with a progressive, hyperpigmented lesion involving the orbit and intracranial
cavity diagnosed as PEM. The case is unique given the young age and the size,
multifocality, and growth of this tumor. Identification of this lesion is
paramount due to its low-grade malignant potential.
PMID- 29344502
TI - Orbital Epstein-Barr Virus-Positive Polymorphic B-Cell Lymphoproliferative
Disorder in an Apparently Immunocompetent Woman.
AB - We report a rare case of Epstein-Barr virus (EBV)-positive polymorphic B-cell
lymphoproliferative disorder (LPD) involving the lacrimal gland of a 28-year-old,
apparently immunocompetent woman. She presented with a chief complaint of orbital
swelling and tenderness and was found to have a lesion involving the right
lacrimal gland and distal superior and lateral rectus muscles. Histology of the
lesion revealed histiocytes with pleomorphic nuclei, reactive lymphocytes, and
scattered cells that resembled the Reed-Sternberg (R-S) cells of classical
Hodgkin lymphoma. The R-S-like cells were positive for PAX5 and CD30 and negative
for CD15, supporting a diagnosis of polymorphic B-cell LPD. In situ hybridization
for EBV-encoded RNA demonstrated the presence of EBV. Most EBV-positive
polymorphic B-cell LPDs are associated with immunodeficiency. However, the
patient described is HIV-negative and has no identifiable defects in
immunoglobulin levels or cell-mediated immunity. This raises the question of
whether she has an underlying immunodeficiency resulting from subtle changes in T
cell physiology, or whether chronic EBV infection contributed to her immune
dysfunction through an unclear mechanism. The orbital mass partially regressed
with chemotherapy, and the patient has done well clinically with no recurrence of
this EBV-LPD for over 2 years.
PMID- 29344504
TI - New Findings on the Pathogenesis of Distal Renal Tubular Acidosis.
AB - Background: Distal renal tubular acidosis (dRTA) is characterized by an
impairment of the urinary acidification process in the distal nephron. Complete
or incomplete metabolic acidosis coupled with inappropriately alkaline urine are
the hallmarks of this condition. Genetic forms of dRTA are caused by loss of
function mutations of either SLC4A1, encoding the AE1 anion exchanger, or
ATP6V1B1 and ATP6V0A4, encoding for the B1 and a4 subunits of the vH+ATPase,
respectively. These genes are crucial for the function of A-type intercalated
cells (A-IC) of the distal nephron. Summary: Alterations of acid-base homeostasis
are variably associated with hypokalemia, hypercalciuria, nephrocalcinosis or
nephrolithiasis, and a salt-losing phenotype. Here we report the diagnostic test
and the underlying physiopathological mechanisms. The molecular mechanisms
identified so far can explain the defect in acid secretion, but do not explain
all clinical features. We review the latest experimental findings on the
pathogenesis of dRTA, reporting mechanisms that are instrumental for the
clinician and potentially inspiring a novel therapeutic strategy. Key Message:
Primary dRTA is usually intended as a single-cell disease because the A-IC are
mainly affected. However, novel evidence shows that different cell types of the
nephron may contribute to the signs and symptoms, moving the focus from a single
cell towards a renal disease.
PMID- 29344503
TI - Genetics of Magnesium Disorders.
AB - Background: Magnesium (Mg2+), the second most abundant cation in the cell, is
woven into a multitude of cellular functions. Dysmagnesemia is associated with
multiple diseases and, when severe, can be life-threatening. Summary: This review
discusses Mg2+ homeostasis and function with specific focus on renal Mg2+
handling. Intrarenal channels and transporters related to Mg2+ absorption are
discussed. Unraveling the rare genetic diseases with manifestations of
dysmagnesemia has greatly increased our understanding of the complex and
intricate regulatory network in the kidney, specifically, functions of tight
junction proteins including claudin-14, -16, -19, and -10; apical ion channels
including: TRPM6, Kv1.1, and ROMK; small regulatory proteins including AC3 and
ANK3; and basolateral proteins including EGF receptor, gamma-subunit (FXYD2) of
Na-K-ATPase, Kir4.1, CaSR, CNNM2, and SLC41A. Although our understanding of Mg2+
handling of the kidney has expanded considerably in the last two decades, many
questions remain. Future studies are needed to elucidate a multitude of unknown
aspects of Mg2+ handling in the kidney. Key Message: Understanding rare and
genetic diseases of Mg2+ dysregulation has expanded our knowledge and furthers
the development of strategies for preventing and managing dysmagnesemia.
PMID- 29344505
TI - Genome-Wide Analysis Studies and Chronic Kidney Disease.
AB - In recent years, the very high worldwide prevalence of chronic kidney disease
(CKD) has led some authors to talk of an "epidemic." The progression of CKD
varies considerably among individuals despite similar aetiologies, optimal blood
pressure, and glycaemic control. Over the last decade, through genome-wide
association studies (GWAS), more than 50 genetic loci have been identified in
association with CKD. Understanding the genetic basis of CKD could provide a
better knowledge of the biology of the involved pathways, thus potentially
leading to novel tools for the diagnosis, prevention, and therapy of CKD. In this
review, we will analyse the role of GWAS in the study of CKD.
PMID- 29344506
TI - MicroRNAs in Renal Diseases: A Potential Novel Therapeutic Target.
AB - Background: MicroRNAs (miRNAs) are a family of short noncoding RNAs that play
important roles in posttranscriptional gene regulation. miRNAs inhibit target
gene expression by blocking protein translation or by inducing mRNA degradation
and therefore have the potential to modulate physiological and pathological
processes. Summary: In the kidney, miRNAs play a role in the organogenesis and in
the pathogenesis of several diseases, including renal carcinoma, diabetic
nephropathy, cystogenesis, and glomerulopathies. Indeed, podocytes, but also the
parietal cells of the Bowman capsule are severely affected by miRNA deregulation.
In addition, several miRNAs have been found involved in the development of renal
fibrosis. These experimental lines of evidence found a counterpart also in
patients affected by diabetic and Ig-A nephropathies, opening the possibility of
their use as biomarkers. Finally, the possibility to direct target-specific miRNA
to prevent the development of renal fibrosis is encouraging potential novel
therapies based on miRNA mimicking or antagonism. This review reports the main
studies that investigate the role of miRNAs in the kidneys, in particular
highlighting the experimental models used, their potential role as biomarkers
and, finally, the most recent data on the miRNA-based therapy. Key Messages:
miRNAs are crucial regulators of cell function. They are easy to detect and
represent potentially good targets for novel therapies.
PMID- 29344507
TI - Definition, Management, and Outcomes of Acute Kidney Injury: An International
Survey of Nephrologists.
AB - Background: Acute kidney injury (AKI) is a complex disease burdened by
uncertainties of definition, management strategies, and prognosis. This study
explores the relationship between demographic characteristics of nephrologists
and their perceptions about the definition, management, and follow-up of AKI.
Methods: We developed a Web-based survey, the International Survey on Acute
Kidney Injury (ISAKI), consisting of 29 items in 4 categories: (1) demographic
and practice characteristics, (2) definition of AKI, (3) management of renal
replacement therapy (RRT) in AKI, and (4) sequelae of AKI. A multivariable
stepwise logistic regression model was used to examine relationships between the
dependent variables and the demographic characteristics of the respondents.
Results: Responses from 743 nephrologists from 90 countries were analyzed. The
majority (60%) of respondents reported using RIFLE and/or AKIN criteria regularly
to define AKI, although US nephrologists were less likely to do so (OR: 0.58; 95%
CI: 0.42-0.85). The most common initial RRT modality was intermittent
hemodialysis (63.5%), followed by continuous RRT (23.8%). Faculty affiliation was
associated with a higher likelihood of using a dialysis schedule of >=4 times a
week (OR: 1.75; 95% CI: 1.20-2.55). The respondents believed that a single
episode of AKI increases the likelihood of development of chronic kidney disease
(CKD) (55%), subsequent AKI (36%), and rapid progression of preexisting CKD
(87%). US nephrologists were less likely to recommend follow-up after resolution
of AKI (OR: 0.15; 95% CI: 0.07-0.33). Conclusions: Our findings highlight the
need for a widely accepted consensus definition of AKI, a uniform approach to
management, and improved follow-up after resolution of AKI episodes.
PMID- 29344508
TI - Acid-Base and Electrolyte Disorders in Patients with and without Chronic Kidney
Disease: An Update.
AB - Kidneys play a pivotal role in the maintenance and regulation of acid-base and
electrolyte homeostasis, which is the prerequisite for numerous metabolic
processes and organ functions in the human body. Chronic kidney diseases
compromise the regulatory functions, resulting in alterations in electrolyte and
acid-base balance that can be life-threatening. In this review, we discuss the
renal regulations of electrolyte and acid-base balance and several common
disorders including metabolic acidosis, alkalosis, dysnatremia, dyskalemia, and
dysmagnesemia. Common disorders in chronic kidney disease are also discussed. The
most recent and relevant advances on pathophysiology, clinical characteristics,
diagnosis, and management of these conditions have been incorporated.
PMID- 29344509
TI - Review of the Diagnostic Evaluation of Normal Anion Gap Metabolic Acidosis.
AB - Background: Normal anion gap metabolic acidosis is a common but often
misdiagnosed clinical condition associated with diarrhea and renal tubular
acidosis (RTA). Early identification of RTA remains challenging for inexperienced
physicians, and diagnosis and treatment are often delayed. Summary: The presence
of RTA should be considered in any patient with a high chloride level when the CL
/Na+ ratio is above 0.79, if the patient does not have diarrhea. In patients with
significant hyperkalemia one should evaluate for RTA type 4, especially in
diabetic patients, with a relatively conserved renal function. A still growing
list of medications can produce RTA. Key Messages: This review highlights
practical aspects concerning normal anion gap metabolic acidosis.
PMID- 29344510
TI - Ablation of FGFR2 in Fibroblasts Ameliorates Kidney Fibrosis after
Ischemia/Reperfusion Injury in Mice.
AB - Background: Fibroblast growth factors (FGFs) are heparin-binding proteins
involved in a variety of biological processes. However, the role and mechanisms
of FGF/FGFR2 signaling in fibroblast activation and kidney fibrosis need further
investigation. Methods: In this study, a mouse model with fibroblast-specific
FGFR2 gene disruption was generated. The knockouts were born normal and no kidney
dysfunction or histological abnormality was found within 2 months after birth. A
kidney ischemia/reperfusion injury (IRI) model was created. Results: Kidney
fibrosis was developed in the control littermates within 2 and 4 weeks after IRI,
while in the knockouts, total collagen deposition, fibronectin, and alpha smooth
muscle actin expression were decreased compared to those in the control
littermates. In addition, the numbers of Ki-67-positive interstitial cells as
well as TUNEL-positive interstitial cells were lower in the knockout kidneys at 4
weeks after IRI. Phosphorylated extracellular regulated protein kinase 1/2 was
decreased in the knockout kidneys at 2 and 4 weeks after IRI compared to those in
the control littermates. Conclusion: These results suggest that FGF/FGFR2
signaling may promote the proliferation and activation of kidney fibroblasts,
which contribute to the development of kidney fibrosis.
PMID- 29344512
TI - Frontiers of Liver Surgery.
PMID- 29344511
TI - Crosstalk of Hyperglycemia and Dyslipidemia in Diabetic Kidney Disease.
AB - Background: Diabetic kidney disease (DKD) is defined by the functional,
structural, and clinical abnormalities of the kidney that are caused by diabetes.
Summary: One-third of both type 1 diabetes and type 2 diabetes patients suffer
from DKD, which is the leading cause of end-stage renal disease, and is also
associated with cardiovascular disease and high public health care costs. Serum
glucose level and lipid level are key factors in the pathogenesis of DKD and are
modifiable. The goal of this review is to provide an update on the roles of
glucose and lipid metabolism in DKD and their crosstalk at the molecular level.
We will further discuss the recent advances regarding metabolic nuclear receptors
in glucose-lipid crosstalk, which may provide new potential therapeutic targets
for DKD. Key Message: AMPK, SREBP-1, and some metabolic hormone receptors
including liver X receptors, farnesoid X receptors, and peroxisome proliferator
activated receptors mediate the crosstalk of hyperglycemia and dyslipidemia in
diabetic kidney disease and might be potential treatment candidates.
PMID- 29344513
TI - 'In-Situ Split' Liver Resection/ALPPS - Historical Development and Current
Practice.
AB - Background: Liver tumors that are extensive, multifocal, or critically located
frequently require advanced techniques of liver resection including '!' -
enabling liver resection in certain situations. Methods: The development of the
technique in the first and the subsequent 8 patients in the index center, and
also the method's spread throughout Germany and the world were reviewed. Results:
In 2007, in the first patient, the new technique was developed intraoperatively
by necessity. Due to the convincing outcome, it was deliberately applied again
several months later in another patient, and thereafter (sparsely) used for liver
resection for various indications. Following oral communication, the method
spread throughout Germany, and later - mainly following the publication of the
initial multicentric German series - very quickly disseminated worldwide.
Currently, it is used for a very (if not overly) broad spectrum of indications by
many hepatobiliary surgery centers. Conclusion: In-situ split/ALPPS is a newly
developed technique for liver resection, which was established for very specific
situations. This method has created a hype, and is currently used rather
generously by many centers worldwide.
PMID- 29344514
TI - Portal Vein Embolization: History and Current Indications.
AB - Portal vein embolization (PVE) was first adapted for patients undergoing major
hepatectomy for hepatocellular carcinoma (HCC). In these patients, PVE caused
hypertrophy of the unaffected liver and increased the volumetric ratio of future
liver remnant (FLR) to total liver volume. 99mTechnetium-galactosyl human serum
albumin (99mTc-GSA) scintigraphy revealed that PVE also induced a shift in
hepatic function from the embolized part to the nonembolized part of the liver.
Various hepatobiliary malignancies can be treated using PVE, and PVE is
increasingly being used to expand the indication for major hepatectomy in
patients with initially insufficient FLR volume or function. The indication for
PVE is determined by the underlying liver function and standardized FLR volume.
In patients with chronic hepatitis, the histologic inflammatory activity was
negatively correlated with the increase in FLR volume, and PVE is not suitable
for patients with high serum 7s collagen concentrations (>8 ng/ml). This finding
may predict the efficacy of PVE. PVE before major hepatectomy can act as a
tolerance test to avoid postoperative hepatic failure. PVE also improved long
term survival after liver resection in patients with HCC. Presently, PVE is a
safe and useful treatment for patients undergoing major hepatectomy.
PMID- 29344515
TI - Portal Vein Embolization: State-of-the-Art Technique and Options to Improve Liver
Hypertrophy.
AB - Portal vein embolization (PVE) is associated with a high technical and clinical
success rate for induction of future liver remnant hypertrophy prior to surgical
resection. The degree of hypertrophy is variable and depends on multiple factors,
including technical aspects of the procedure and underlying chronic liver
disease. For patients with insufficient liver volume following PVE, adjunctive
techniques, such as intra-portal administration of stem cells, dietary
supplementation, transarterial embolization, and hepatic vein embolization, are
available. Our purpose is to review the state-of-the-art technique associated
with high-quality PVE and to discuss options to improve hypertrophy of the future
liver remnant.
PMID- 29344516
TI - Hypertrophy and Liver Function in ALPPS: Correlation with Morbidity and
Mortality.
AB - Background: ALPPS (associating liver partition and portal vein ligation for
staged hepatectomy) was introduced with the promise to reduce posthepatectomy
liver failure (PHLF) in extended hepatectomies but has higher morbidity and
mortality rates compared to conventional methods of volume enhancement. There are
few studies of the incidence of PHLF after ALPPS and little information on how to
avoid PHLF by functional testing. It remains unclear what causes the compromise
in liver function despite rapid volume gain and if any of the modifications
proposed reduce the incidence of PHLF. This review summarizes published data on
this topic. Methods: This is a systematic review that studies literature on the
incidence of liver failure and assessment of liver function following ALPPS as
well as modifications of the existing technique. Articles were searched in
PubMed, evaluated, selected, and tabulated. Results: The literature search
revealed 326 articles that met the selection criteria. PHLF criteria as defined
by the International Study Group of Liver Surgery (ISGLS) were the most commonly
used criteria, but PHLF was frequently not defined. PHLF occurred most frequently
after stage 2 of ALPPS at around 30% in most larger studies. Hepatobiliary
scintigraphy showed a discrepancy between volume and functional growth of the
liver. Function increase was only 50% compared to volume increase. Mechanistic
explanations using histologic analyses have been given to explain the immaturity
of the liver after rapid hypertrophy. Modifications of ALPPS showed a comparable
volumetric gain when compared to classic ALPPS, but data were lacking to assess
PHLF. Conclusion: ALPPS has relatively high rates of PHLF, morbidity, and
mortality. This may be explained by data demonstrating functional growth when
compared to volume growth. ALPPS should not be performed without functional
assessment and with caution.
PMID- 29344517
TI - A Comparison of Pitfalls after ALPPS Stage 1 or Portal Vein Embolization in Small
for-Size Setting Hepatectomies.
AB - Background: Portal vein embolization (PVE) followed by resection and associating
liver partition and portal vein ligation for staged hepatectomy (ALPPS) are tools
to enable liver resections in small-for-size settings. Methods: A systematic
review of the literature and comparison of pitfalls between PVE and resection and
after ALPPS stage 1 were performed. Results: Evidence levels were as low as 4 for
both procedures. 20 publications were identified with reports on post-PVE or post
ALPPS stage 1 pitfalls. A total of 2,758 patients treated with PVE followed by
resection and 698 patients undergoing ALPPS were analyzed. Pitfalls identified
were failure to advance to resection (PVE: high (20%)/ALPPS: low (1%); p =
0.0001), tumor progression (PVE: high/ALPPS: low); insufficient hypertrophy (PVE:
frequent/ALPPS: rare), and inter-stage liver failure (PVE: rare/ALPPS: frequent).
However, in-house mortality was still very high after ALPPS (7 vs. 3%, p =
0.0001) in a pooled analysis. Conclusion: PVE is a well-established technique to
induce hypertrophy in small-for-size settings. The weakness of PVE is that it may
fail to advance to resection. Inter-stage liver failure in ALPPS triggers post
stage 2 mortality. Prolongation of the inter-stage interval to overcome liver
failure or cancellation of the resection stage combined with adherence to defined
indications has the potential to make ALPPS much safer and decrease mortality
rates. Level of evidence is low for both techniques.
PMID- 29344518
TI - Current Modalities for the Assessment of Future Remnant Liver Function.
AB - While imaging studies such as computed tomography or magnetic resonance imaging
allow the volumetric assessment of the liver segments, only indirect information
is provided concerning the quality of the liver parenchyma and its actual
functional capacity. Assessment of liver function is therefore crucial in the
preoperative workup of patients who require extensive liver resection and in whom
portal vein embolization is considered. This review deals with the modalities
currently available for the measurement of liver function. Passive liver function
tests include biochemical parameters and clinical grading systems such as the
Child-Pugh and MELD scores. Dynamic quantitative tests of liver function can be
based on clearance capacity tests such as the indocyanine green (ICG) clearance
test. Although widely used, discrepancies have been reported for the ICG
clearance test in relation with clinical outcome. Nuclear imaging studies have
the advantage of providing simultaneous morphologic (visual) and physiologic
(quantitative functional) information about the liver. In addition, regional
(segmental) differentiation allows specific functional assessment of the future
remnant liver. Technetium-99m (99mTc)-galactosyl human serum albumin scintigraphy
and 99mTc-mebrofenin hepatobiliary scintigraphy potentially identify patients at
risk for post-resectional liver failure who might benefit from liver-augmenting
techniques. As there is no one test that can measure all the components of liver
function, liver functional reserve is estimated based on a combination of
clinical parameters and quantitative liver function tests.
PMID- 29344519
TI - ICG Clearance Test and 99mTc-GSA SPECT/CT Fusion Images.
AB - Preoperative estimation of future remnant liver function is critical for major
hepatic surgery to avoid postoperative morbidity and mortality. Among several
liver function tests, the indocyanine green (ICG) clearance test is still the
most popular dynamic method. The usefulness of ICG clearance test parameters,
such as ICGR15, KICG, or PDRICG, has been reported by many investigators. The
transcutaneous non-invasive pulse dye densitometry system has made the ICG
clearance test more convenient and attractive, even in Western countries. The
concept of future remnant KICG (rem KICG), which combines the functional aspect
and the volumetric factor of the future remnant liver, seems ideal for
determining the maximum extent of major hepatic resection that will not cause
postoperative liver failure. For damaged livers with functional heterogeneity
among the hepatic segments, fusion images combining technetium-99m
diethylenetriaminepentaacetic acid-galactosyl human serum albumin single photon
emission computed tomography (99mTc-GSA SPECT) and X-ray CT are helpful to
precisely estimate the functional reserve of the future remnant liver. Another
technique for image-based liver function estimation, gadolinium ethoxybenzyl
diethylenetriamine pentaacetic acid(Gd-EOB)-enhanced magnetic resonance imaging,
may be an ideal candidate for the preoperative determination of future remnant
liver function. Using these methods effectively, morbidity and mortality after
major hepatic resection could be reduced.
PMID- 29344521
TI - Frontiers of Liver Surgery.
PMID- 29344520
TI - Did the International ALPPS Meeting 2015 Have an Impact on Daily Practice? The
Hamburg Barmbek Experience of 58 Cases.
AB - Background: ALPPS (associating liver partition and portal vein ligation for
staged hepatectomy) was introduced only 10 years ago and has gained wide
acceptance as a variation of staged procedures in liver surgery. It has been
criticized for its high morbidity and mortality, which all centers reported in
their initial series. Methods: After a world expert meeting in Hamburg in 2015
where all experts in the field met to discuss this method, caveats were extracted
and formulated. We researched our complete prospective ALPPS database to see if
the recommendations had any impact on outcome. Results: In total, we performed 58
ALPPS procedures in our center. 33 patients were operated on before, 25 after the
meeting. Results in terms of morbidity and mortality were significantly better
after the meeting, as were patient selection and strategy. Conclusion: In our own
center's experience, the implementation of the meetings' recommendations and the
information gathered through this valuable exchange had a dramatic impact on
results. Having performed 58 ALPPS procedures in total, we can now conclude that
ALPPS has become much safer in our hands since the 2015 meeting and that
morbidity and mortality are no longer the issue to be discussed. Future research
must focus on oncologic outcomes in these patients.
PMID- 29344524
TI - The Professionalization of Iranian hospital social Workers.
AB - Introduction: Identity is formed through our understanding of ourselves and what
others perceive of our actions and how we do things. Formation of professional
identity includes development, advancement and socialization through social
learning of specific knowledge and skills obtained within the context of
professional roles, new attitudes and values. Methods: This qualitative study
used content analysis approach to explain the professionalization process of 22
social workers working in 14 public hospitals in Tehran based on their
experiences. The data were collected through semi-structured interviews,
observation and writing in the field. Results: Eleven categories and three themes
of entry into the profession, identity formation, and identity ownership were
extracted out of data analysis. Revealing the process, barriers and facilitators
of professionalization of hospital social workers was the results of this study.
Conclusion: Certain individual characteristics were factors for the tendency of
participants to choose this profession. The participants' understanding of their
profession was formed, when studying in the university through learning relevant
knowledge, skills, views and professional expectations. Achieving a single
identity and professional pride and self-esteem are achievements of identity
ownership.
PMID- 29344522
TI - Intraductal Papillary Mucinous Neoplasms of the Pancreas: Strategic
Considerations.
AB - Intraductal papillary mucinous neoplasms (IPMN) are cystic neoplasms with the
potential for progression to pancreatic cancer. Recognized by the global medical
community just over two decades ago, IPMN have gained great epidemiological and
clinical relevance thanks to the widespread use of cross-sectional abdominal
imaging, which has led to a surge in the number of incidental pancreatic cysts
being diagnosed. As our understanding of this disease has improved, we now know
that some IPMN have a very elevated risk of cancer and require surgical
resection, while others are low-risk lesions and can be followed. The approach to
IPMN must therefore strike a balance between preventing the over-utilization of
surgery and the timely recognition and treatment of patients with high-risk
lesions. Several clinical, radiographic, and laboratory parameters have been
proposed to risk-stratify IPMN, leading to the publication of management
guidelines that do not always converge in their recommendations. The goal of this
clinical therapeutic review is to describe the strategic approach to IPMN at the
Massachusetts General Hospital, and how our current understanding, management
algorithm, and future directions have been informed by research efforts at our
institution and other centers.
PMID- 29344523
TI - Clinical skills temporal degradation assessment in undergraduate medical
education.
AB - Introduction: Medical students' ability to learn clinical procedures and
competently apply these skills is an essential component of medical education.
Complex skills with limited opportunity for practice have been shown to degrade
without continued refresher training. To our knowledge there is no evidence that
objectively evaluates temporal degradation of clinical skills in undergraduate
medical education. The purpose of this study was to evaluate temporal retention
of clinical skills among third year medical students. Methods: This was a cross
sectional study conducted at four separate time intervals in the cadaver
laboratory at a public medical school. Forty-five novice third year medical
students were evaluated for retention of skills in the following three
procedures: pigtail thoracostomy, femoral line placement, and endotracheal
intubation. Prior to the start of third-year medical clerkships, medical students
participated in a two-hour didactic session designed to teach clinically relevant
materials including the procedures. Prior to the start of their respective
surgery clerkships, students were asked to perform the same three procedures and
were evaluated by trained emergency medicine and surgery faculty for retention
rates, using three validated checklists. Students were then reassessed at six
week intervals in four separate groups based on the start date of their
respective surgical clerkships. We compared the evaluation results between
students tested one week after training and those tested at three later dates for
statistically significant differences in score distribution using a one-tailed
Wilcoxon Mann-Whitney U-test for non-parametric rank-sum analysis. Results:
Retention rates were shown to have a statistically significant decline between
six and 12 weeks for all three procedural skills. Conclusion: In the instruction
of medical students, skill degradation should be considered when teaching complex
technical skills. Based on the statistically significant decline in procedural
skills noted in our investigation, instructors should consider administering a
refresher course between six and twelve weeks from initial training.
PMID- 29344525
TI - Psychometric properties of the communication skills attitude scale (CSAS) measure
in a sample of Iranian medical students.
AB - Introduction: Communication skill (CS) has been regarded as one of the
fundamental competencies for medical and other health care professionals.
Student's attitude toward learning CS is a key factor in designing educational
interventions. The original CSAS, as positive and negative subscales, was
developed in the UK; however, there is no scale to measure these attitudes in
Iran. The aim of this study was to assess the psychometric characteristic of the
Communication Skills Attitude Scale (CSAS), in an Iranian context and to
understand if it is a valid tool to assess attitude toward learning communication
skills among health care professionals. Methods: Psychometric characteristics of
the CSAS were assessed by using a cross-sectional design. In the current study,
410 medical students were selected using stratified sampling framework. The face
validity of the scale was estimated through students and experts' opinion.
Content validity of CSAS was assessed qualitatively and quantitatively.
Reliability was examined through two methods including Chronbach's alpha
coefficient and Intraclass Correlation of Coefficient (ICC). Construct validity
of CSAS was assessed using confirmatory factor analysis (CFA) and explanatory
factor analysis (PCA) followed by varimax rotation. Convergent and discriminant
validity of the scale was measured through Spearman correlation. Statistical
analysis was performed using SPSS 19 and EQS, 6.1. Results: The internal
consistency and reproducibility of the total CSAS score were 0.84 (Cronbach's
alpha) and 0.81, which demonstrates an acceptable reliability of the
questionnaire. The item-level content validity index (I-CVI) and the scale-level
content validity index (S-CVI/Ave) demonstrated appropriate results: 0.97 and
0.94, respectively. An exploratory factor analysis (EFA) on the 25 items of the
CSAS revealed 4-factor structure that all together explained %55 of the variance.
Results of the confirmatory factor analysis indicated an acceptable goodness-of
fit between the model and the observed data. [chi2/df = 2.36, Comparative Fit
Index (CFI) = 0.95, the GFI=0.96, Root Mean Square Error of Approximation (RMSEA)
= 0.05]. Conclusion: The Persian version of CSAS is a multidimensional, valid and
reliable tool for assessing attitudes towards communication skill among medical
students.
PMID- 29344527
TI - Medical students' experiences and perspective on unprofessional behavior in
clinical practice.
AB - Introduction: Recognition of professional and unprofessional behaviors is the
most important and fundamental factor which affects the relationships between the
doctors and patients. Therefore, in order to progress in their professional life,
doctors are supposed to understand and follow these behaviors. Methods: This is a
cross-sectional, descriptive analytical study. All students in teaching hospital
of Shiraz University of Medical Sciences were eligible to participate (374
individuals with census method). The data were collected using a questionnaire
containing 29 questions about the concept of medical professionalism. Here,
participation of medical students in unprofessional behaviors and the relevance
of this participation with the perception of these behaviors were considered.
Data were analyzed through SPSS version 15, using descriptive statistics, t-test
and Pearson correlation test. Results: According to the obtained data, despite
the fact that all students (140 students in the junior and 234 in the senior
years as interns) had passed the course of professionalism (95.7%), the
perception of unprofessional behaviors between the two groups was significantly
different (p<0.001) and the mean of the perception among junior students was
higher than the interns. No significant difference was observed in participation
in unprofessional behavior rates of the two groups (p=0.451).Moreover, the data
did not reveal a strong relationship between participation in unprofessional
behavior and what is taught in the curriculum (p=0.079). Conclusion: Medical
students' perception of unprofessional behaviors as acceptable may increase their
participation in these behaviors. Thus, medical policy makers should consider
approaches beyond simply providing ethical and professional guidelines or
policies, and students should be regularly evaluated for their activities; their
professional behaviors should be evaluated in order to temper them, when
appropriate.
PMID- 29344526
TI - The effects of team-based learning on learning outcomes in a course of
rheumatology.
AB - Introduction: We evaluated the effects of implementing Team-Based Learning (TBL)
on student engagement, accountability, satisfaction, and preference for lecture
or team-based learning. Moreover, we assessed the effect of TBL on knowledge
retention and application over time through short answer questions based on
clinical scenarios addressing history taking and diagnosis skills in medical
students. Methods: The study was conducted in a quasi-experimental design. The
study population were all of the third-year medical students (n = 84)
participating in a course of rheumatology in Shariati Hospital, which is a
teaching hospital affiliated to Tehran University of Medical Sciences. We
compared TBL with the conventional lecture-based method. The assessments were
performed after implementation of TBL by the Classroom Engagement Survey (CES)
and Team-Based Learning Student Assessment Instrument (TBL-SAI). The assessment
for application of knowledge was conducted in 3 time-points through short answer
questions on rheumatic diseases. The comparison of results was made by Student's
t-test and repeated-measures analysis of variance (RM-ANOVA) using SPSS software,
version 16. Results: The CES scores indicated a high level of engagement in TBL
(Mean+/-SD=26.7+/-3.70, p=0.0001) but not in the lecture-based sessions (Mean+/
SD=23.80+/-4.35, p=0.09). The total mean score (SD) for TBL-SAI was 159.68
(14.14) for TBL sessions indicating a favorable outcome (p=0.0001). The student
scores obtained from the short answer questions showed that over time the
students' scores had declined significantly less for the TBL sessions in
comparison to the lecture-based sessions, F (2, 166) = 4.624, p=0.011.
Conclusion: The results indicated higher student engagement, satisfaction and
long term learning by TBL.
PMID- 29344528
TI - Psychometric characteristics of Clinical Reasoning Problems (CRPs) and its
correlation with routine multiple choice question (MCQ) in Cardiology department.
AB - Introduction: Clinical reasoning is one of the most important skills in the
process of training a medical student to become an efficient physician.
Assessment of the reasoning skills in a medical school program is important to
direct students' learning. One of the tests for measuring the clinical reasoning
ability is Clinical Reasoning Problems (CRPs). The major aim of this study is to
measure psychometric qualities of CRPs and define correlation between this test
and routine MCQ in cardiology department of Shiraz medical school. Methods: This
study was a descriptive study conducted on total cardiology residents of Shiraz
Medical School. The study population consists of 40 residents in 2014. The
routine CRPs and the MCQ tests was designed based on similar objectives and were
carried out simultaneously. Reliability, item difficulty, item discrimination,
and correlation between each item and the total score of CRPs were all measured
by Excel and SPSS software for checking psycometeric CRPs test. Furthermore, we
calculated the correlation between CRPs test and MCQ test. The mean differences
of CRPs test score between residents' academic year [second, third and fourth
year] were also evaluated by Analysis of variances test (One Way ANOVA) using
SPSS software (version 20)(alpha=0.05). Results: The mean and standard deviation
of score in CRPs was 10.19 +/-3.39 out of 20; in MCQ, it was 13.15+/-3.81 out of
20. Item difficulty was in the range of 0.27-0.72; item discrimination was 0.30
0.75 with question No.3 being the exception (that was 0.24). The correlation
between each item and the total score of CRP was 0.26-0.87; the correlation
between CRPs test and MCQ test was 0.68 (p<0.001). The reliability of the CRPs
was 0.72 as calculated by using Cronbach's alpha. The mean score of CRPs was
different among residents based on their academic year and this difference was
statistically significant (p<0.001). Conclusion: The results of this present
investigation revealed that CRPs could be reliable test for measuring clinical
reasoning in residents. It can be included in cardiology residency assessment
programs.
PMID- 29344529
TI - Internationalization of medical education in Iran: A way towards implementation
of the plans of development and innovation in medical education.
AB - Introduction: Academic institutions are the most important organizations for
implementation of internationalization policies and practices for integrating an
international, intercultural and global dimension in higher education system.
Also, a globally increasing demand for higher education has been seen in the past
two decades so that the number of students enrolled in higher education
institutions in the worldwide nation-states has increased dramatically. The
National Plan of International Development of Medical Education was designed with
the aim of identifying available potentials in all the universities of medical
sciences, encouraging the development of international standards of medical
education, and planning for the utilization of the existing capacity in Islamic
republic of Iran. Methods: Authors have tried to review the several aspects of
international activities in higher education in the world and describe national
experiences and main policies in globalization of medical education in Iran
within implementation of the National Plan for Development and Innovation in
Medical Education. Results: The findings of some global experiences provide the
policy makers with clear directions in order to develop internationalization of
higher education. Conclusion: The Program for International Development of
Medical Education was designed by the Deputy of Education in the Ministry of
Health and the effective implementation of this Program was so important for
promotion of Iranian medical education. But there were some challenges in this
regard; addressing them through inter-sectoral collaboration is one of the most
important strategies for the development of internationalization of education in
the field of medical sciences.
PMID- 29344530
TI - Female role models in medicine: a medical student's perspective.
PMID- 29344531
TI - Factors Affecting the Place of Delivery among Mothers Residing in Jhorahat VDC,
Morang, Nepal.
AB - Background: In Nepal, the maternal mortality ratio is 281 per thousand live
births, among which 40% mortality occurs during home delivery. Home delivery
increases the risk of maternal and neonatal mortality and morbidity due to the
birth not assisted by skilled attendant. This study was carried out to determine
the factors affecting the place of delivery among the mothers residing in
Jhorahat VDC, Morang district, Nepal. Methods: A mixed method study using
interviews based on semi-structured questionnaire (n=93) among mothers and two
focus group discussion among decision makers of the house and female community
health volunteers was conducted between November to December 2012. For
quantitative data, Chi-square test and Fischer's Exact test were used to examine
the association between the selected variables and place of delivery. Results:
More than half (58.1%) of the mothers had institutional delivery and 41.9% of
them had home delivery. The most common reason for home delivery was easy and
convenient environment (66.7%) and that for institutional delivery was safety
(77.8%). There was a significant association between caste, education of mothers,
education of spouse, occupation of spouse, per capita income, time to reach the
nearest health center, parity, previous place of delivery, number of antenatal
visit, knowledge about place of delivery, planned place of delivery, and place of
delivery. Conclusion: Maternal health services, such as prenatal care, skilled
assistance during delivery and post-natal care, along with adequately equipped
health institutions, play a major role in the reduction of maternal morbidity and
mortality. Concerted efforts should be made both at community and government
levels to increase institutional delivery.
PMID- 29344532
TI - Functional Ability of Clients with Bipolar Disorders in Tertiary Hospital,
Puducherry.
AB - Background: Bipolar Disorder (BD) is a common long standing mental illness which
is episodic in nature, affecting approximately1-2% of the world adult population.
BD frequently affects the patient's life. Few studies have examined the
functional impairment in patients with affective illness. The main objective of
the current study was to assess specific domains of functioning as well as the
overall functioning of the clients with BD. Methods: This cross-sectional study
aimed to assess the level of function among the clients with BD in JIPMER
Hospital, Puducherry during 2015-2016 and to identify the socio- demographic and
clinical factors associated with the level of functioning. Ninety clients who
fulfilled the inclusion criteria of having the diagnosis of BD were selected
after written informed consents were obtained. After collecting basic demographic
and clinical variables, function was assessed using 2 different sets of tools
LIFE-RIFT and FAST. Data were analyzed using SPSS 20. Independent sample t-test,
ANOVA and Pearson correlation were used as different statistical methods. A P
value less than .05 was considered as statistically significant. Results: Based
on the results, the functional level assessed using LIFE -RIFT showed a mean
score of 26.7+/-4.7for the admitted clients and 21+/-12.5 for outpatients. The
functional level of clients was significantly related to admission and remission
status of the clients with a P=0.001 Similarly, FAST scale score for the admitted
clients was 51+/-4.5, clients on remission had 24+/-12.1 with a P=0.001.
Conclusion: Results revealed that even during remission the clients with BD had
functional impairment. More interventions are needed to improve the functional
ability of clients with BD.
PMID- 29344533
TI - The Effect of Family-Centered Empowerment Program on Self-Efficacy of Adolescents
with Thalassemia Major: A Randomized Controlled Clinical Trial.
AB - Background: Chronic nature of thalassemia causes changes in different aspects of
life in patients, including their self-efficacy. The aim of this study was to
determine the effect of family-centered empowerment program on the self-efficacy
of adolescents with Thalassemia major. Methods: A quasi-experimental study was
performed on adolescents with thalassemia major in 2013 in Bandar Abbas, Iran.
The participants were divided into intervention and control groups, respectively.
Research instruments included demographic data questionnaire, need assessment
self-made questionnaire, general self-efficacy scale, and sickle cell self
efficacy scale. After collecting the data from the pre-intervention step, family
centered empowerment program was implemented for the intervention group and
secondary test was conducted six weeks after the intervention and the results
were analyzed by statistical SPSS-21 software, using independent t-test, paired t
test, Chi-square and Fisher's exact test, and descriptive statistics. A
significance level of P<0.05 was considered as significant. Results: The mean and
standard deviation of the adolescents' age were 16+/-1.9 in the intervention
group and 15.2+/-2 in the control group. Independent t-test showed a significant
difference between the two groups after the intervention for both self-efficacies
(P<0.01 and P=0.02). In the control group, the results of general self-efficacy
scores after six weeks' time were reduced compared to the previous one while
disease-related self-efficacy scores in the same group after six weeks' time
increased and paired t-test indicated a significant difference in the mean scores
for both self-efficacies in both groups. Conclusion: Implementation of family
centered empowerment program for patients with thalassemia major is practically
feasible and it can increase self-efficacy in these patients. It is suggested
that the program should be used in comprehensive care protocols of children and
adolescents. Trial Registration Number: IRCT201407211788N8.
PMID- 29344534
TI - The Effect of Self-Care Education on Emotional Intelligence and HbA1c level in
Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Clinical Trial.
AB - Background: The role of Emotional Intelligence (EI) in glycemic control in type 2
Diabetes Mellitus (DM) has not been fully understood. The present study aimed to
investigate the effect of self-care education on EI and hemoglobin glycosylated
(HbA1c) in patients with type 2 diabetes. Methods: In this randomized controlled
clinical trial, 48 patients with type 2 DM referred to Shahid Motahari Diabetes
Center in 2015 were divided into an intervention and a control group using block
randomization. The study data were collected using Bar-On questionnaire and blood
testing immediately and two months after the intervention. The educational
content was presented to the intervention group through 1-1:30-hour sessions held
once a week for 8 continuous weeks. The control group, however, only received the
clinic's routine cares. Results: The results showed a significant difference in
the mean level of HbA1c in the intervention group before and two months after the
intervention (P=0.003). However, this difference was not significant in the
control group. Moreover, the mean of EI was higher in the intervention group
compared to the control group (P=0.08). Conclusion: Self-care education improved
the HbA1c level and EI among the patients with type 2 DM. Therefore, it is
recommended that health care providers, specially nurses, should train the
diabetic patients for self-care, which can lead to better glycemic control. Trial
Registration Number: IRCT201408188505N7.
PMID- 29344535
TI - Sexual Experience of Iranian Women in Their Middle Life: A Qualitative Approach.
AB - Background: Sexual problems are common among the middle-aged women; however,
there is no deep understanding of sexuality in midlife. The current study aimed
to investigate Iranian women's attitudes and experiences about sexual life
changes in midlife. Methods: This is a descriptive qualitative study. Seventeen
women aged 40 -65 years old were purposively selected from urban health centers
in Gorgan, Iran, in 2015. Face-to-face, semi-structured and in-depth interviews
were conducted for data collection until data saturation was attained. The
resulting data were analyzed based on Graneheim and Lundman's approach. MAXQDA 10
was used for organization of data. Results: Data analysis demonstrated seventh
sub-themes and three themes. The emerged themes were entitled (1) "Continuous
paradox over being a sexual agent" with three subthemes of beliefs on asexuality
as socially accepted view for women in midlife, changing in motivation for sex
and changing in sexual performance, (2) "Considering menopause; opportunities and
threats for sexual life" with two subthemes of menopause related cons for sexual
life and menopause related pros in sexual life, and (3) "Coping strategies for
changes in sexuality in midlife" with two subthemes of different psychological
reactions to changes that have influenced the sex and take practical steps for
restoration of sexual attraction. Conclusion: The findings demonstrated that
middle-aged women in a male-dominant culture encounter paradox over being a
sexual agent. In a bio-psycho-social approach, they perceived menopause as an
opportunity or threat for their own sexuality. Following the conflicts, threats
and changes of sexuality in midlife, they adopt diverse coping strategies to
improve their sexual relationships and preserve their family.
PMID- 29344536
TI - A Cry for Help and Protest: Self-Immolation in Young Kurdish Iraqi Women -A
Qualitative Study.
AB - Background: Suicide is a major psychiatric emergency that has always been a topic
of great interest to researchers. Self-immolation is a heinous suicide method
that is common in Eastern societies. The present study was conducted to explore
probable issues which might lead to self-immolation in young Kurdish Iraqi women.
Methods: The present qualitative study was conducted in Soran, Erbil Governorate
in Iraq, and the surrounding villages of Soran District (March 2015 to May 2016).
Using purposive sampling, we conducted 24 in-depth interviews with women who had
done self-immolation. The obtained data were analyzed using conventional content
analysis. Results: The analysis of the data obtained from the interviews led to
the extraction of five categories which seems to be related to self-immolation
attempts, including not having control over personal life, marital conflicts,
seeking attention, instilling guilt in the family members, and resentment towards
male dominant community. Conclusion: Self-immolation is a multidimensional
phenomenon that has not come to exist overnight and is rooted in various factors
that join to encourage self-immolation attempts by women in critical situations.
Comprehensive preventive strategies, such as cultural changes, along with
education are required to help lower the rate of self-immolation.
PMID- 29344537
TI - The Relationship between Health Literacy and Health Promoting Behaviors in
Patients with Type 2 Diabetes.
AB - Background: Health promoting behaviors are known to be a key factor in managing
type 2 diabetes and improving the quality of life in diabetic patients. However,
there is little known about the factors influencing these behaviors in diabetic
patients. This study aimed to find the relationship between the health literacy
and health promoting behaviors in patients with type II diabetes. Methods: This
correlational study was conducted from August to September 2016 on 175 eligible
diabetic patients (20 to 65 year-old) who referred to the selected centers of
diabetes control in Ahvaz City. Patients were chosen using convenience non
probable sampling. Data were collected by diabetic patients' health promoting
behaviors' questionnaire and health literacy questionnaire. Data were analyzed
using SPSS 22, descriptive statistics and Pearson's correlation coefficient.
Result: The mean scores for health promoting behaviors and health literacy were
determined 100.45+/-19.82 and 76.14+/-15.26, respectively. The highest and lowest
scores in health promoting behaviors belonged to nutrition (26.11+/-6.85) and
physical activity (6.70+/-2.75), respectively. There was a significant
relationship between all dimensions of health promoting behaviors and health
literacy (P<0.05). Conclusion: Since health literacy has a positive relationship
with health promoting behaviors in diabetic patients, health care providers need
to concentrate on increasing the health literacy of their patients rather than
solely concentrating on increasing their knowledge, thereby facilitating the
development of health promoting behaviors in patients.
PMID- 29344538
TI - Lived Experiences of Mothers with Diabetic Children from the Transfer of Caring
Role.
AB - Background: Following the confirmed type 1 diabetes in children and their
discharge from the hospital, the care responsibilities are transferred from
nurses to mothers. These mothers are faced with many challenges to play this
caring role. The aim of this study was to explore the experiences of the diabetic
children's mothers from the transfer of caring role. Methods: In 2016, semi
structured interviews with Eleven Iranian mothers of children (aged<=14 year)
with type 1 diabetes were conducted. Data were analyzed using Colizzi's
phenomenological method. Results: The following themes emerged in this study:
'Facing the care management challenges,' 'care in the shadow of concern', and
'hard life in the impasse of diabetes'. Conclusion: The mothers of children with
type 1 diabetes, who undertake the caring role that has been transferred to them
by healthcare providers, are faced with many challenges. They feel a lot of
concerns and experience a hard life. Thus, understanding the experiences of these
mothers by the health professionals, to improve the quality of care, is
necessary.
PMID- 29344539
TI - Agreement between Heart Failure Patients and Their Primary Caregivers on Symptom
Assessment.
AB - Background: To decrease the readmission rate of heart failure (HF) patients,
patients and their caregivers (CGs) should participate in symptoms assessment.
This study aimed to assess the agreement between HF patients and their CGs on
symptoms assessment. Methods: Using a correlational design, 100 HF patients with
their CGs (100 dyads) were recruited from Department of Cardiology, Iranshahr,
during August-December 2014. Data were collected using modified Heart Failure
Symptom Survey (HFSS).Pearson and intra-class correlation coefficients (ICC) were
used to analyze the degree of agreement within HF dyads, using SPSS16. The level
of significance was set at 0.05. Results: The most frequent and severe symptom
assessed equally by partners was shortness of breath (SOB). Dyads had a good
agreement on assessment of extremity swelling (r=0.87, P<=0.01, ICC=0.861 CI:
0.798-0.901), SOB at rest (r=0.83, P<=0.01, ICC=0.775, CI: 0.680-0.845), SOB with
activity (r=0.81, P<=0.01, ICC=0.795 CI: 0.711-0.858), and feeling depressed
(r=0.77, P<=0.01, ICC=0.769, CI: 0.675-0.838). 28.6% of HF dyad had a good, 50%
had a moderate, and 21.4 % had a poor agreement in assessment of HF symptoms.
Conclusion: Most of the HF dyad members did not agree with each other on the
assessment of symptoms. Knowledge, skills and ability of each dyad in HF symptoms
assessment should be included in the patients' discharge planning and nurses must
modify their misunderstanding or inability.
PMID- 29344540
TI - Standing Height as a Prevention Measure for Overuse Injuries of the Back in
Alpine Ski Racing: A Kinematic and Kinetic Study of Giant Slalom.
AB - Background: In alpine ski racing, typical loading patterns of the back include a
combined occurrence of spinal bending, torsion, and high peak loads. These
factors are known to be associated with high spinal disc loading and have been
suggested to be attributable to different types of spine deterioration. However,
little is known about the effect of standing height (ie, the distance between the
bottom of the running surface of the ski and the ski boot sole) on the
aforementioned back loading patterns. Purpose: To investigate the effect of
reduced standing height on the skier's overall trunk kinematics and the acting
ground-reaction forces in giant slalom (GS) from an overuse injury prevention
perspective. Study Design: Controlled laboratory study. Methods: Seven European
Cup-level athletes skied a total of 224 GS turns with 2 different pairs of skis
varying in standing height. Their overall trunk movement (frontal bending,
lateral bending, and torsion angles) was measured based on 2 inertial measurement
units located at the sacrum and sternum. Pressure insoles were used to determine
the total ground-reaction force. Results: During the turn phase in which the
greatest spinal disc loading is expected to occur, significantly lower total
ground-reaction forces were observed for skis with a decreased standing height.
Simultaneously, the skier's overall trunk movement (ie, frontal bending, lateral
bending, and torsion angles) remained unwaveringly high. Conclusion: Standing
height is a reasonable measure to reduce the skier's overall back loading in GS.
Yet, when compared with the effects achievable by increased gate offsets in
slalom, for instance, the preventative benefits of decreased standing height seem
to be rather small. Clinical Relevance: To reduce the magnitude of overall back
loading in GS and to prevent overuse injuries of the back, decreasing standing
height might be an efficient approach. Nevertheless, the clinical relevance of
the current findings, as well as the effectiveness of the measure "reduced
standing height," must be verified by epidemiological studies before its
preventative potential can be judged as conclusive.
PMID- 29344541
TI - Bony Maturity of the Tibial Tuberosity With Regard to Age and Sex and Its
Relationship to Pathogenesis of Osgood-Schlatter Disease: An Ultrasonographic
Study.
AB - Background: Although tensile force on an immature tibial tuberosity is considered
the main cause of Osgood-Schlatter disease (OSD), the relationship between bony
maturity and the pathogenesis of OSD remains obscure. Purpose: To survey the bone
maturation process of the tibial tuberosity by age and sex and clarify its
relationship to OSD. Study Design: Cross-sectional study; Level of evidence, 3.
Methods: A total of 731 Japanese basketball players aged 6 to 14 years were
enrolled in this study. Ultrasonographic examination was performed in all
participants (1462 knees) to evaluate the bony maturity of the tibial tuberosity
by use of the Ehrenborg classification. The age- and sex-specific prevalence of
each stage was investigated, and the prevalence of symptomatic OSD and its
relationship with bony maturity were also assessed. Results: The process of bone
maturation occurred 1 to 2 years earlier in female participants compared with
male participants. Among female participants, 59.2% were already at the
epiphyseal stage (stage E) by 10 years of age, and 47.4% were skeletally mature
by 14 years. Among male participants, conversely, only 8.0% were at stage E by 10
years of age, and only 13.8% were skeletally mature by 14 years. The overall
prevalence of symptomatic OSD was 6.8% (males, 6.4%; females, 7.2%), and the
onset was 1 year earlier in the female participants. The prevalence of
symptomatic OSD tended to increase with age and bony maturity, significantly
increasing from the cartilaginous stage (stage C) to the apophyseal stage (stage
A) (odds ratio, 9.48) and from stage A to stage E (odds ratio, 2.22). Conclusion:
The tibial tuberosity matures earlier in female participants. The risk of OSD is
greater in stage A than stage C and in stage E than stage A. The risk of OSD
increases with age in males but not in females.
PMID- 29344542
TI - Ruxolitinib for essential thrombocythemia?
PMID- 29344543
TI - Targeting H(i)ck education for cancer therapy?
PMID- 29344544
TI - Multiple pro-tumor roles for protein acyltransferase DHHC3.
PMID- 29344545
TI - In vivo pieces of the PP2A onco-puzzle fallen into place.
PMID- 29344546
TI - RUNX3 loss turns on the dark side of TGF-beta signaling.
PMID- 29344547
TI - Mesenchymal stem cells in breast cancer: response to chemical and mechanical
stimuli.
PMID- 29344548
TI - Recombinant ADAMTS 13 in thrombotic thrombocytopenic purpura.
PMID- 29344549
TI - E-cadherin and K-ras: implications of a newly developed model of gastric cancer.
PMID- 29344550
TI - Neutrophils and anti-cancer immunity: a paradigm shift in cancer immunotherapy.
PMID- 29344551
TI - Cell-autonomous and non-autonomous functions of S100A4 in regulating stemness,
mesenchymal transition, and metastasis.
PMID- 29344552
TI - Collagen and Calcium Binding EGF Domains 1 (CCBE1) in cancer - a new role past
lymphatics?
PMID- 29344553
TI - Reprogramming patient-derived tumor cells generates model cell lines for tuberous
sclerosis-associated lymphangioleiomyomatosis.
PMID- 29344554
TI - Pulling the plug - halting cancer's theft of mitochondria.
PMID- 29344555
TI - Destroying the androgen receptor (AR)-potential strategy to treat advanced
prostate cancer.
PMID- 29344556
TI - Extracellular matrix composition modulates angiosarcoma cell attachment and
proliferation.
AB - Angiosarcoma is a rare and generally fatal tumor composed of aberrant cells of
endothelial origin. Because of its infrequency in humans, very little is known
about the growth requirements of this vascular sarcoma. Unlike the rapidly
proliferating solid tumors from which they are isolated from, many of the
established angiosarcoma cell lines exhibit less than robust growth in culture
and often fail to form tumors in xenograft models. In order to better understand
angiosarcoma in vitro growth conditions, we focused on a singular aspect of their
culture-adhesion to the extracellular matrix-in order to identify attachment
substrates that may facilitate and/or enhance their growth in tissue culture. Our
data indicates that the extracellular matrix of angiosarcomas contains similar
protein compositions to that of non-diseased endothelial cells. Moreover,
angiosarcoma cell lines exhibited strong attachment preference to substrates such
as collagen I or fibronectin, and less preference to collagen IV, laminin, or
tropoelastin. Growth on preferred extracellular matrix substrates promoted
mitogenic signaling and increased proliferation of angiosarcoma cell lines. These
findings provide insight that may lead to more successful in vitro growth of
angiosarcoma cell lines.
PMID- 29344557
TI - In colonic rho0 (rho0) cells reduced mitochondrial function mediates
transcriptomic alterations associated with cancer.
AB - Background: Mitochondrial reprogramming has emerged as a hallmark of cancer
pathobiology. Although it is believed this reprogramming is essential for cancer
cells to thrive, how it supports cancer pathobiology is unclear. We previously
generated colonic rho0 (rho0) cells with reduced mitochondrial energy function
and acquired their transcriptional signature. Here, we utilized a bioinformatics
approach to identify their changes linked to cancer pathobiology. Methods: Human
colon cancer HCT116 cells, control and rho0, were used for qPCR. Bioinformatics
analysis: GeneCards, Kaplan-Meier Survival, GENT, cBioPortal. Results: The
colonic rho0 transcriptome was linked with proliferation, DNA replication,
survival, tumor morphology, and cancer. Among differentially expressed
transcripts, 281 were regulators or biomarkers of human colon cancer especially
those with inflammatory microsatellite instability (MSI). We identified and
validated novel transcripts in rho0 cells with altered expression in human colon
cancer. Among them DGK1, HTR7, FLRT3, and ZBTB18 co-occurred with established
regulators of human colon cancer pathobiology. Also, increased levels of DGKI,
FLRT3, ZBTB18, and YPEL1 as well as decreased levels of HTR7, and CALML6 were
linked to substantially poorer patient survival. Conclusion: We identified
established and novel regulators in colon cancer pathobiology that are dependent
on mitochondrial energy reprogramming and linked to poorer patient survival.
PMID- 29344558
TI - Therapeutic potential of bleomycin plus suicide or interferon-beta gene transfer
combination for spontaneous feline and canine melanoma.
AB - We originated and characterized melanoma cell lines derived from tumors of two
feline and two canine veterinary patients. These lines reestablished the
morphology, physiology and cell heterogeneity of their respective parental
tumors. We evaluated the cytotoxicity of bleomycin (BLM) alone, or combined with
interferon-beta (IFN-beta) or HSVtk/GCV suicide gene (SG) lipofection on these
cells. Although the four animals presented stage III disease (WHO system), SG
treated feline tumors displayed stable disease in vivo, while the canine ones
exhibited partial response. Their derived cell lines reflected this behavior.
Feline were significantly more sensitive than canine cells to IFN-beta gene
transfer. BLM improved the antitumor effects of both genes. The higher levels of
reactive oxygen species (ROS) significantly correlated with membrane and DNA
damages, emphasizing ROS intervention in apoptotic and necrotic cell death. After
3 days of BLM alone or combined with gene treatments, the colony forming capacity
of two canine and one feline treatments survivor cells almost disappeared. Taken
together, these results suggest that the treatments eradicated tumor initiating
cells and support the clinical potential of the tested combinations.
PMID- 29344559
TI - Infant Feeding Regimens and Gastrointestinal Tolerance: A Multicenter,
Prospective, Observational Cohort Study in China.
AB - To study feeding tolerance in infants fed formula with increased sn-2 palmitate
and oligofructose (sn-2+OF) in a real-world setting, healthy Chinese infants were
enrolled in this 48-day observational study on their current feeding regimens:
exclusively breastfed (BF; n = 147), exclusively sn-2+OF formula-fed (FF; n =
150), or mixed-fed with breast milk and sn-2+OF formula (MF; n = 163). Throughout
the study, incidence (90% confidence interval) of hard stools was <=2.1% (0.0
5.3) in FF and 0.8% (0.0-3.5) in MF, with no hard stools in BF. Incidence of
watery stools was <=5.0% (1.0-9.2) in FF and >=5.1% (2.4-9.3) in MF and BF.
Gastrointestinal tolerance scores, although low in all groups (lower scores
indicating better tolerance), were slightly higher (P >= .03) in FF (17.5 +/-
4.8) and MF (18.2 +/- 5.0) versus BF (16.3 +/- 3.2) at mid-study; this difference
disappeared at study end. Overall, low incidences of hard and watery stools and
good feeding tolerance were observed in infants fed sn-2+OF formula.
PMID- 29344560
TI - Nonbilious Vomiting in a 4-Week-Old Male: A Case Report and Review of the
Literature.
PMID- 29344561
TI - Self-expandable metal stent placement in a child for treatment of achalasia after
failed Heller myotomy.
AB - Background and study aims Childhood achalasia treatment remains inconclusive.
What is next after myotomy failure? Repeated pneumatic-dilation put patients at
greater risk of perforation with possible symptom recurrence. We report on a 12
year-old patient with a 1-year history of achalasia whom underwent Heller myotomy
with fundoplication and recurred with symptoms 1 week after surgery. Pneumatic
dilatation was considered but not done because of the risk of esophageal
perforation. The decision was made to place a fully covered self-expanding
metallic stent (FC-SEMS) for 3 months, which resolved the stenosis as confirmed
by esophagram. The patient has remained asymptomatic since the procedure was
performed 2 years ago. FC-SEMS is an alternative for treatment of refractory
achalasia in children who do not respond to conventional treatment.
PMID- 29344562
TI - Endoscopic ultrasound-guided choledochoduodenostomy using partially-covered self
expandable metal stent in patients with malignant distal biliary obstruction and
unsuccessful ERCP.
AB - Background and study aims : Endoscopic ultrasound-guided choledochoduodenostomy
(EUS-CDS) is an alternative to percutaneous transhepatic biliary drainage (PTBD)
for patients with malignant distal biliary obstruction in whom ERCP has failed.
We studied technical success, clinical success, stent patency rate and occurrence
of adverse events in patients undergoing EUS-CDS with partially-covered self
expanding metal stent (PCSEMS). Patients and methods : Medical records of
consecutive patients with unresectable malignant distal biliary obstruction
requiring biliary drainage who underwent EUS-CDS because of failure of attempt at
ERCP were reviewed. EUS-CDS was done using 6-cm, PCSEMS (Wallflex, Boston
Scientific). Technical success, clinical success (more than 50 % reduction in
total bilirubin at 2 weeks post-procedure), stent patency rate and adverse events
(AEs) were assessed. Patients were followed up for 3 months post-procedure.
Results : Between January 2015 and December 2016, 30 patients underwent EUS-CDS,
including 20 (67 %) with failed biliary cannulation and 10 (33 %) with duodenal
stenosis. Technical success was achieved in 28 patients, all of whom also had
clinical success. Median total serum bilirubin decreased from 20 mg/dL to 5 mg/dL
at 2 weeks post-procedure. Three patients (10 %) had adverse events (bile leak,
hemobilia, stent block in one patient each; no stent migration); none of these
adverse events was major and all were managed successfully. There were no
procedure-related deaths. Five patients died of disease progression in the 3
month period post-procedure, and the 3-month dysfunction-free stent patency rate
was 83 %. Conclusion : EUS-CDS with a PCSEMS has a high technical and clinical
success. Adverse events were infrequent, minor and could be managed easily.
PMID- 29344563
TI - The use of fully-covered self-expanding metallic stents for intraprocedural
management of post-sphincterotomy perforations: a single-center study (with
video).
AB - Background and study aims : Management of post-sphincterotomy perforations is
variable, with some patients managed conservatively and other requiring surgery.
Fully-covered self-expanding metal stents (FCSEMs) have been used in the past,
but data is limited. The aim of this study was to report the clinical
characteristics and outcomes following placement of anchored FCSEMSs for the
immediate management of post-sphincterotomy perforation. Patients and methods :
All patients undergoing an ERCP procedure between June 2011 and December 2015 at
our institution were reviewed for post-sphincterotomy perforation. All intra
procedurally recognized perforations underwent placement of FCSEMs with flexible
anchoring fins and were included in this study. Data extracted included patient
demographics, indication, peri-procedural details, clinical course and long-term
outcome following anchored FCSEMS placement. Results : A total of 15 patients (12
females, median age-66 years) with post-sphincterotomy perforation were included.
Major indications included choledocholithiasis in 9 (60 %), and 5 (33.3 %)
patients had intra-ampullary or periampullary diverticula. All patients underwent
placement of FCSEMS without any complication and had immediate resolution of
perforation as evidenced by decrease in fluoroscopic gas and lack of contrast
extravasation. None of the patients became symptomatic or needed surgery with a
median 2 days of hospitalization following the procedure. Stents were removed
after a median of 30.5 days and no complications were noted during follow-up
after stent removal. Conclusions : Anchored FCSEMs are safe and effective for
management of intra-procedurally recognized post-sphincterotomy perforations and
obviates need for surgery.
PMID- 29344564
TI - Endoscopic ultrasound guided needle-based confocal laser endomicroscopy in solid
pancreatic masses - a prospective validation study.
AB - Background and study aims: Endoscopic ultrasound fine-needle aspiration (EUS
FNA) is a keystone in diagnosing and staging of pancreatic masses. Recently, a
microfiber that can pass through a 19-gauge needle has been introduced for
confocal laser endomicroscopy (nCLE). The aims of this study were to evaluate the
diagnostic value and the reproducibility of nCLE criteria for solid malignant
lesions. Patients and methods: This prospective dual-center study included
patients with pancreatic masses suspicious of malignancy referred for EUS-FNA.
Endomicroscopic imaging was performed under EUS-guidance until organ-specific
structures were obtained. Afterwards, standard cytology was obtained and patients
were followed for up to 12 months. All nCLE parameters included in former studies
were correlated with the final diagnosis (dark lobular structures/normal acinar
cells, dark cell aggregates > 40 um, dilated irregular vessels with fluorescein
leakage, fine white fibrous bands, small black cell movements, pseudoglandular
structures). Finally, three CLE novices and three CLE experts assessed the
unedited movies from all patients. Results: Twenty-eight patients were enrolled
in the study. A final diagnosis was obtained in 24 patients (86 %). One patient
(3 %) died before a diagnosis was obtained, while 3 were lost to follow-up (11
%). In 18/24 patients (74 %) the diagnosis was malignant. The mean sensitivity,
specificity, and accuracy for the nCLE parameters ranged from 19 - 93 %, 0 - 56
%, 26 - 69 %, respectively. The inter-observer values ranged from kappa = 0.20 -
0.41 for novices and kappa = -0.02 - 0.38 for experts. Conclusions: The
diagnostic value of nCLE in solid pancreatic masses is questionable and the inter
observer agreement for both novices and CLE experts appears limited.
PMID- 29344565
TI - A novel method of endoscopic-assisted esophageal clearance in advanced achalasia.
AB - Background and study aims : In order to perform peroral endoscopic myotomy (POEM)
safely, retained liquid and food debris must be removed before the procedure is
started. We developed a novel technique using a super-slim gastroscope, and a
gastric tube to remove retained food debris in achalasia patients. In this study,
the safety and efficacy of this novel technique were investigated. Patients and
methods : Eleven patients with achalasia were enrolled in this study and
underwent this novel method for esophageal clearance. Results: All patients had
complete clearance of the retained food debris using this method. The median
procedure time (range) was 13 (6 - 30) minutes. There were no serious adverse
events (AEs) and one minor AE of mucosal erythema due to mucosal suctioning.
Conclusion: This novel method for esophageal clearance is safe and effective in
achalasia patients with large amounts of retained food debris.
PMID- 29344567
TI - Response to letter to the editor - "Training in ERCP: a multifaceted enterprise
now more than ever".
PMID- 29344566
TI - Training in ERCP: a multifaceted enterprise now more than ever.
PMID- 29344568
TI - Non-surgical management of Boerhaave's syndrome: a case series study and review
of the literature.
AB - Background and study aims: Boerhaave's syndrome (BS) is a life-threatening
condition with morbidity and mortality rates as high as 50 % in some reports.
Until recently, surgical intervention has been the mainstay of management plans.
With advances in therapeutic endoscopy, however, there has been increasing
interest in non-surgical options including endoscopic esophageal stenting.
Patients and methods: We reviewed the medical records of all patients diagnosed
with BS and managed with endoscopic interventions between November 2011 and
November 2016. The following variables were collected: patient demographics,
clinical presentations, locations of esophageal perforation, primary
interventions, complications, and outcomes. Results: Six patients were found to
be diagnosed with BS during the study period. The median age at presentation was
55. There were 4 males and 2 females. The most common site of perforation was in
the distal esophagus. The most common presenting symptom was chest pain (67 %)
following an episode of vomiting or retching. Four patients (66.7 %) developed
septic shock. Endoscopic treatment with a fully covered esophageal stent was the
primary intervention in all patients (100 %). Interventional radiology was
consulted in all cases for fluid drainage and chest tube placements. Clinical
resolution of the BS was achieved in all patients (100 %) without any subsequent
surgical interventions. There were no deaths within the study group, and the
average follow-up duration was 2 years. Conclusion: Endoscopic treatment seems
to be an effective management strategy in patients with BS. We also noted
satisfactory results in patients presenting with sepsis, presumably due to
urgent, interventional radiology-guided fluid drainage.
PMID- 29344569
TI - Endoscopic full-thickness resection with an over-the-scope clip device (FTRD) in
the colorectum: results from a university tertiary referral center.
AB - Background and study aims: The full-thickness resection device (FTRD) represents
a novel endoscopic treatment method for lesions unresectable with conventional
endoscopic techniques. The overall aim of this study was to evaluate technical
success and in toto resection rates, recurrence rates, as well as immediate or
late complications in patients who underwent polyp removal with the FTRD.
Patients and methods: Data from a prospectively collected database of 12
patients who underwent 13 over-the-scope clip-based full-thickness resections
between June 2015 and June 2017 were analyzed. Follow-up endoscopy was performed
in 11 out of 12 patients. Results: 13 full-thickness resections were performed
in 7 males and 5 females (mean age 64.3 +/- 6.3 years). Mean size of the lesions
removed with FTRD was 17 +/- 4 mm. Location was rectum (n = 6), cecum (n = 2),
ascending colon (n = 2), left flexure (n = 1) and right flexure (n = 2). Mean
procedure time was 68 +/- 35 minutes and mean hospital stay was 2.5 +/- 1.2 days.
2 patients developed post-polypectomy syndrome, which resolved after conservative
treatment. No perforations and no immediate surgical revision were needed.
Histology of the 13 lesions removed with FTRD showed 5 adenomas with low grade
intraepithelial neoplasia (IEN), 4 high grade IEN, 1 fibrosis, 1 fibrosis without
dysplasia and 2 adenocarcinomas. Technical success was achieved in all procedures
(13/13, 100 %). R0 resection was achieved in 10/12 patients (83.3 %). 2 patients
underwent surgery because of recurrence or not evaluable margins. In 1 patient no
residual malignancy was proven in histological examination, in the other patient
residual low grade IEN adenoma. Conclusion: FTRD is a minimally invasive
approach with good success rate of complete resection and minimal side effects.
PMID- 29344570
TI - Use of anticoagulant or antiplatelet agents is not related to epistaxis in
patients undergoing transnasal endoscopy.
AB - Background and study aims : Unsedated transnasal endoscopy (uTNE) has become
accepted as a safe and tolerable method for upper gastrointestinal tact
examinations. Epistaxis is 1 of the major complications of TNE, though its risk
factors have not been elucidated. Generally, patients administered an
anticoagulant or antiplatelet drug are considered to have an increased risk of
epistaxis during TNE. Here, we investigated risk factors of epistaxis in patients
undergoing uTNE, with focus on those who received antithrombotic agents. Patients
and methods : We enrolled 6860 patients (average age 55.6 +/- 12.97 years; 3405
males, 3455 females) who underwent uTNE and received the same preparations for
the procedure. Epistaxis was evaluated using endoscopic images obtained while
withdrawing the scope through the nostril. We also noted current use of
medications including anticoagulant or antiplatelet agents prior to the
endoscopic examination. Results : Epistaxis occurred in 3.6 % of the enrolled
patients (245/6860), and that rate was significantly higher in younger patients
(average age 49.31 +/- 11.8 years for epistaxis group vs. 55.83 +/- 13.0 years
for no epistaxis group, P < 0.01) as well as females (4.78 % vs. 2.35 %, P <
0.01). The odds ratio for occurrence of epistaxis was 2.31 (95 %CI: 1.746 -
3.167) in the younger patients and 2.02 (95 % CI: 1.542 - 2.659) in females. In
contrast, there was no significant difference for rate of epistaxis between
patients with and without treatment with an antithrombotic agent (3.0 % vs. 3.6
%). Conclusions : The rate of epistaxis was higher in younger and female
patients. Importantly, that rate was not significantly increased in patients who
were administered an antithrombotic agent.
PMID- 29344571
TI - Underwater endoscopic mucosal resection: a new endoscopic method for resection of
rectal neuroendocrine tumor grade 1 (carcinoid) <= 10 mm in diameter.
AB - Background and study aims Rectal neuroendocrine tumors grade 1 (NET G1;
carcinoid) <= 10 mm in diameter often extend into the submucosa, making their
complete histological resection difficult using endoscopic techniques. Endoscopic
submucosal resection with a ligation device (ESMR-L) and endoscopic submucosal
dissection (ESD) are commonly used to overcome these difficulties. We also
previously reported that underwater endoscopic mucosal resection (UEMR) could
facilitate resection of rectal NET G1. This study aimed to evaluate the safety
and efficacy of UEMR for removing rectal NET G1 <= 10 mm in diameter. 6
consecutive patients with rectal NET G1 <= 10 mm in diameter underwent UEMR at
our hospital. The rate of en bloc resection was 100 %, and the rate of R0
resection was 83 %. The median procedure time was 8 min (range 5 - 12 min). No
perforations or delayed bleeding occurred in this study. In conclusion, UEMR
allows the safe and reliable resection of rectal NET G1 <= 10 mm in diameter with
comparable results to ESMR-L or ESD, including high en bloc and R0 resection
rates with no increase in significant adverse events. A multicenter trial is
required to confirm the validity of the present results.
PMID- 29344572
TI - Expert-led didactic versus self-directed audiovisual training of confocal laser
endomicroscopy in evaluation of mucosal barrier defects.
AB - Background and study aims: Confocal laser endomicroscopy (CLE) allows mucosal
barrier defects along the intestinal epithelium to be visualized in vivo during
endoscopy. Training in CLE interpretation can be achieved didactically or through
self-directed learning. This study aimed to compare the effectiveness of expert
led didactic with self-directed audiovisual teaching for training inexperienced
analysts on how to recognize mucosal barrier defects on endoscope-based CLE
(eCLE). Materials and methods: This randomized controlled study involved trainee
analysts who were taught how to recognize mucosal barrier defects on eCLE either
didactically or through an audiovisual clip. After being trained, they evaluated
6 sets of 30 images. Image evaluation required the trainees to determine whether
specific features of barrier dysfunction were present or not. Trainees in the
didactic group engaged in peer discussion and received feedback after each set
while this did not happen in the self-directed group. Accuracy, sensitivity, and
specificity of both groups were compared. Results : Trainees in the didactic
group achieved a higher overall accuracy (87.5 % vs 85.0 %, P = 0.002) and
sensitivity (84.5 % vs 80.4 %, P = 0.002) compared to trainees in the self
directed group. Interobserver agreement was higher in the didactic group (k =
0.686, 95 % CI 0.680 - 0.691, P < 0.001) than in the self-directed group (k =
0.566, 95 % CI 0.559 - 0.573, P < 0.001). Confidence (OR 6.48, 95 % CI 5.35 -
7.84, P < 0.001) and good image quality (OR 2.58, 95 % CI 2.17 - 2.82, P <
0.001) were positive predictors of accuracy. Conclusion: Expert-led didactic
training is more effective than self-directed audiovisual training for teaching
inexperienced analysts how to recognize mucosal barrier defects on eCLE.
PMID- 29344573
TI - Development of an external-to-internal convertible endoscopic biliary drainage
device - a preliminary prospective feasibility study.
AB - Background and study aims: Endoscopic nasobiliary drainage (ENBD) for a
malignant stricture in the bile duct has some advantages over endoscopic biliary
stenting (EBS). However, ENBD may cause nasopharyngeal discomfort. We developed
an external-to-internal convertible endoscopic biliary drainage (ETI-EBD) device
that enables both internal and external drainage to occur during a single
endoscopy. Patients and methods : This device consists of three parts, comprising
a 5-Fr ENBD tube (250 cm) (ENBD-t), an 8.5-Fr EBS tube (7 cm) (EBS-t), and an 8
Fr pusher tube for EBS (230 cm) (P-t). The EBS-t is mounted over the ENBD-t at
the distal end of the ENBD-t. The P-t is also placed over the ENBD-t. After an
endoscopic sphincterotomy, the EBS-t of the device is inserted into the papilla,
then the duodenal endoscope is withdrawn, leaving the device in place. After
ENBD, only the ENBD-t was withdrawn from the P-t. At this point, the EBS-t was
isolated and left without endoscopy or radiography. Results : ETI-EBD was
successfully placed in all consecutive 21 patients (100 %). The release of EBS-t
from ENBD-t wit was successfully completed in 19 patients (90.5 %). There were 4
patients with kink of P-t when exchanging this device from the mouth to the nose.
It was difficult for 2 patients to withdraw the ENBD-t because of poor
lubrication performance. There were no significant complications associated with
the use of the device. Conclusion : This device allows for both external and
internal biliary drainage with a single endoscopy.
PMID- 29344574
TI - Observation of spin-orbit magnetoresistance in metallic thin films on magnetic
insulators.
AB - A magnetoresistance (MR) effect induced by the Rashba spin-orbit interaction was
predicted, but not yet observed, in bilayers consisting of normal metal and
ferromagnetic insulator. We present an experimental observation of this new type
of spin-orbit MR (SOMR) effect in the Cu[Pt]/Y3Fe5O12 (YIG) bilayer structure,
where the Cu/YIG interface is decorated with nanosize Pt islands. This new MR is
apparently not caused by the bulk spin-orbit interaction because of the
negligible spin-orbit interaction in Cu and the discontinuity of the Pt islands.
This SOMR disappears when the Pt islands are absent or located away from the
Cu/YIG interface; therefore, we can unambiguously ascribe it to the Rashba spin
orbit interaction at the interface enhanced by the Pt decoration. The numerical
Boltzmann simulations are consistent with the experimental SOMR results in the
angular dependence of magnetic field and the Cu thickness dependence. Our finding
demonstrates the realization of the spin manipulation by interface engineering.
PMID- 29344575
TI - Mammary Myofibroblastoma in a Transgender Patient on Feminizing Hormones:
Literature Review and Case Report.
AB - Purpose: Defining the risk of neoplasia associated with gender-affirming hormone
therapy (GAHT) is a priority for transgender medical research. The purposes of
this article are to present a unique case of breast neoplasia in a transgender
individual and to review the existing evidence base on GAHT as a potential risk
for breast pathology. Methods: We present the case of a 76-year-old transgender
patient who developed an estrogen receptor-positive mammary myofibroblastoma
(MFB) after 13 months of treatment on feminizing hormones. To our knowledge, this
is the first reported case of MFB occurring in a transgender individual. A
literature review was conducted to identify all reported cases of breast
neoplasia among transgender individuals receiving feminizing GAHT. Information
was abstracted from each of the included cases to describe the existing body of
literature and to compare published cases to the case reported in this study.
Results: We identified a total of 19 malignant and 3 benign cases of breast
neoplasia among transgender women. Ours is the first reported case of MFB in a
transgender individual receiving feminizing hormones and the first reported case
of breast neoplasia associated with GAHT administered via the estradiol patch.
Conclusion: This case reinforces the need for additional reporting of breast
neoplasia presenting in transgender individuals treated with feminizing hormones.
The relationship between estrogen exposure and breast neoplasia in the
transgender population remains poorly defined, and additional research is needed
to define risks and inform clinical practice.
PMID- 29344576
TI - Clinical Exposure to Transgender Medicine Improves Students' Preparedness Above
Levels Seen with Didactic Teaching Alone: A Key Addition to the Boston University
Model for Teaching Transgender Healthcare.
AB - Purpose: Transgender individuals are medically underserved in the United States
and face many documented disparities in care due to providers' lack of education,
training, and comfort. We have previously demonstrated that specific transgender
medicine content in a medical school curriculum increases students' willingness
to treat transgender patients. However, we have also identified that those same
students are less comfortable with transgender care relative to care for lesbian,
gay, and bisexual patients. We aimed to demonstrate that clinical exposure to
care for transgender patients would help close this gap. Methods: At Boston
University School of Medicine, we piloted a transgender medicine elective where
students rotate on services that provide clinical care for transgender
individuals. Pre- and postsurveys were administered to students who participated
in the elective. Results: After completing the elective, students who reported
"high" comfort increased from 45% (9/20) to 80% (16/20) (p=0.04), and students
who reported "high" knowledge regarding management of transgender patients
increased from 0% (0/20) to 85% (17/20) (p<0.001). Conclusion: Although
integrating evidence-based, transgender-specific content into medical curricula
improves student knowledge and comfort with transgender medical care, gaps
remain. Clinical exposure to transgender medicine during clinical years can
contribute to closing that gap and improving access to care for transgender
individuals.
PMID- 29344577
TI - A Practical Approach to Using Trend Arrows on the Dexcom G5 CGM System for the
Management of Adults With Diabetes.
AB - After reviewing previously published methods, we developed a practical approach
to adjusting insulin doses based on insulin sensitivity for adult patients with
diabetes using rtCGM trend arrow data.
PMID- 29344578
TI - A Practical Approach to Using Trend Arrows on the Dexcom G5 CGM System to Manage
Children and Adolescents With Diabetes.
AB - After assessing previously published methods, we developed a practical approach
to adjusting insulin doses using rtCGM trend arrows in pediatric patients with
diabetes.
PMID- 29344579
TI - Prognostic significance of cytogenetic heterogeneity in patients with newly
diagnosed multiple myeloma.
AB - We investigated subclonal cytogenetic aberrations (CA) detected by interphase
fluorescence in situ hybridization (iFISH) in patients with newly diagnosed
multiple myeloma (MM) enrolled in the Haemato Oncology Foundation for Adults in
the Netherlands (HOVON)-65/German-Speaking MM Group (GMMG)-HD4 phase 3 trial.
Patients were either treated with 3 cycles of vincristine, Adriamycin, and
dexamethasone or bortezomib, Adriamycin, and dexamethasone and then thalidomide
or bortezomib maintenance after tandem autologous transplantation. Subclones were
defined either by presence of different copy numbers of the same chromosome loci
and/or CA present in at least 30% less and maximally 2/3 of cells compared with
the main clone CA. Patients with subclones harbored more frequently high risk
(31.0%) or hyperdiploid main clone aberrations (24.8%) than patients with
t(11;14) in the main clone (10.1%). Gains and deletions of c-MYC were the only CA
that occurred more frequently as subclone (8.1%/20.5%) than main clone
(6.2%/3.9%, respectively). Treatment with bortezomib completely overcame the
negative prognosis of high-risk CA in patients without subclones, but not in
patients with additional subclonal CA. High-risk patients treated without
bortezomib showed dismal outcome whether subclones were present or not.
Cytogenetic heterogeneity defined by subclonal CA is of major prognostic
significance in newly diagnosed MM patients treated with bortezomib within the
HOVON-65/GMMG-HD4 trial.
PMID- 29344580
TI - Successful treatment with fingolimod of graft-versus-host disease of the central
nervous system.
AB - Fingolimod could be efficient to treat GVHD of the central nervous system.Further
research should explore the use of fingolimod and other sphingosine-1-phosphate
receptor agonists to prevent or treat GVHD.
PMID- 29344581
TI - Glycophorin-C sialylation regulates Lu/BCAM adhesive capacity during erythrocyte
aging.
AB - Lutheran/basal cell adhesion molecule (Lu/BCAM) is a transmembrane adhesion
molecule expressed by erythrocytes and endothelial cells that can interact with
the extracellular matrix protein laminin-alpha5. In sickle cell disease, Lu/BCAM
is thought to contribute to adhesion of sickle erythrocytes to the vascular wall,
especially during vaso-occlusive crises. On healthy erythrocytes however, its
function is unclear. Here we report that Lu/BCAM is activated during erythrocyte
aging. We show that Lu/BCAM-mediated binding to laminin-alpha5 is restricted by
interacting, in cis, with glycophorin-C-derived sialic acid residues. Following
loss of sialic acid during erythrocyte aging, Lu/BCAM is released from
glycophorin-C and allowed to interact with sialic acid residues on laminin
alpha5. Decreased glycophorin-C sialylation, as observed in individuals lacking
exon 3 of glycophorin-C, the so-called Gerbich phenotype, was found to correlate
with increased Lu/BCAM-dependent binding to laminin-alpha5. In addition, we
identified the sialic acid-binding site within the third immunoglobulin-like
domain within Lu/BCAM that accounts for the interaction with glycophorin-C and
laminin-alpha5. Last, we present evidence that neuraminidase-expressing
pathogens, such as Streptococcus pneumoniae, can similarly induce Lu/BCAM
mediated binding to laminin-alpha5, by cleaving terminal sialic acid residues
from the erythrocyte membrane. These results shed new light on the mechanisms
contributing to increased adhesiveness of erythrocytes at the end of their
lifespan, possibly facilitating their clearance. Furthermore, this work may
contribute to understanding the pathology induced by neuraminidase-positive
bacteria, because they are especially harmful to patients suffering from sickle
cell disease and are associated with the occurrence of vaso-occlusive crises.
PMID- 29344582
TI - Factor XIII in plasma, but not in platelets, mediates red blood cell retention in
clots and venous thrombus size in mice.
AB - The transglutaminase factor XIII (FXIII) stabilizes clots against mechanical and
biochemical disruption and is essential for hemostasis. In vitro and in vivo
models of venous thrombosis demonstrate that FXIII mediates clot size by
promoting red blood cell (RBC) retention. However, the key source of FXIII and
whether FXIII activity can be reduced to suppress thrombosis without imposing
deleterious hemostatic consequences are 2 critical unresolved questions. FXIII is
present in multiple compartments, including plasma (FXIIIplasma) as a
heterotetramer of A2 and B2 subunits and platelets (FXIIIplt) as an A2 homodimer.
We determined the role of the FXIII compartment and level in clot contraction,
composition, and size in vitro and using in vivo models of hemostasis and venous
thrombosis. Reducing overall FXIII levels decreased whole blood clot weight but
did not alter thrombin generation or contraction of platelet-rich plasma clots.
In reconstituted platelet-rich plasma and whole blood clot contraction assays,
FXIIIplasma, but not FXIIIplt, produced high-molecular-weight fibrin crosslinks,
promoted RBC retention, and increased clot weights. Genetically imposed reduction
of FXIII delayed FXIII activation and fibrin crosslinking, suggesting FXIII
levels mediate the kinetics of FXIII activation and activity and that the timing
of these processes is a critical determinant of RBC retention during clot
formation and contraction. A 50% reduction in FXIIIplasma produced significantly
smaller venous thrombi but did not increase bleeding in tail transection or
saphenous vein puncture models in vivo. Collectively, these findings suggest that
partial FXIII reduction may be a therapeutic strategy for reducing venous
thrombosis.
PMID- 29344584
TI - Early and late outcomes after cord blood transplantation for pediatric patients
with inherited leukodystrophies.
AB - Leukodystrophies (LD) are devastating inherited disorders leading to rapid
neurological deterioration and premature death. Hematopoietic stem cell
transplantation (HSCT) can halt disease progression for selected LD. Cord blood
is a common donor source for transplantation of these patients because it is
rapidly available and can be used without full HLA matching. However, precise
recommendations allowing care providers to identify patients who benefit from
HSCT are lacking. In this study, we define risk factors and describe the early
and late outcomes of 169 patients with globoid cell leukodystrophy, X-linked
adrenoleukodystrophy, and metachromatic leukodystrophy undergoing cord blood
transplantation (CBT) at an European Society for Blood and Marrow Transplantation
center or at Duke University Medical Center from 1996 to 2013. Factors associated
with higher overall survival (OS) included presymptomatic status (77% vs 49%; P =
.006), well-matched (<=1 HLA mismatch) CB units (71% vs 54%; P = .009), and
performance status (PS) of >80 vs <60 or 60 to 80 (69% vs 32% and 55%,
respectively; P = .003). For patients with PS<=60 (n = 20) or 60 to 80 (n = 24)
pre-CBT, only 4 (9%) showed improvement. Of the survivors with PS >80 pre-CBT,
50% remained stable, 20% declined to 60 to 80, and 30% to <60. Overall, an
encouraging OS was found for LD patients after CBT, especially for those who are
presymptomatic before CBT and received adequately dosed grafts. Early
identification and fast referral to a specialized center may lead to earlier
treatment and, subsequently, to improved outcomes.
PMID- 29344583
TI - Heterozygous RTEL1 variants in bone marrow failure and myeloid neoplasms.
AB - Biallelic germline mutations in RTEL1 (regulator of telomere elongation helicase
1) result in pathologic telomere erosion and cause dyskeratosis congenita.
However, the role of RTEL1 mutations in other bone marrow failure (BMF) syndromes
and myeloid neoplasms, and the contribution of monoallelic RTEL1 mutations to
disease development are not well defined. We screened 516 patients for germline
mutations in telomere-associated genes by next-generation sequencing in 2
independent cohorts; one constituting unselected patients with idiopathic BMF,
unexplained cytopenia, or myeloid neoplasms (n = 457) and a second cohort
comprising selected patients on the basis of the suspicion of
constitutional/familial BMF (n = 59). Twenty-three RTEL1 variants were identified
in 27 unrelated patients from both cohorts: 7 variants were likely pathogenic, 13
were of uncertain significance, and 3 were likely benign. Likely pathogenic RTEL1
variants were identified in 9 unrelated patients (7 heterozygous and 2
biallelic). Most patients were suspected to have constitutional BMF, which
included aplastic anemia (AA), unexplained cytopenia, hypoplastic myelodysplastic
syndrome, and macrocytosis with hypocellular bone marrow. In the other 18
patients, RTEL1 variants were likely benign or of uncertain significance.
Telomeres were short in 21 patients (78%), and 3' telomeric overhangs were
significantly eroded in 4. In summary, heterozygous RTEL1 variants were
associated with marrow failure, and telomere length measurement alone may not
identify patients with telomere dysfunction carrying RTEL1 variants.
Pathogenicity assessment of heterozygous RTEL1 variants relied on a combination
of clinical, computational, and functional data required to avoid
misinterpretation of common variants.
PMID- 29344585
TI - Hereditary folate malabsorption due to a mutation in the external gate of the
proton-coupled folate transporter SLC46A1.
AB - Hereditary folate malabsorption (HFM) is an autosomal recessive disorder
characterized by impaired intestinal folate absorption and impaired folate
transport across the choroid plexus due to loss of function of the proton-coupled
folate transporter (PCFT-SLC46A1). We report a novel mutation, causing HFM,
affecting a residue located in the 11th transmembrane helix within the external
gate. The mutant N411K-PCFT was stable, trafficked to the cell membrane, and had
sufficient residual activity to characterize the transport defect and the
structural requirements at this site for gate function. The influx Vmax of the
N411K mutant was markedly decreased, as was the affinity for most, but not all,
folate/antifolate substrates. The greatest loss of activity was for 5
methyltetrahydrofolate. Substitutions with positive charged residues resulted in
a loss of activity (arginine > lysine > histidine). Function was retained for the
negative charged aspartate, but not the larger glutamate substitutions, whereas
the bulky hydrophobic (leucine), or polar (glutamine) substitutions, were
tolerated. Homology models of PCFT, in the inward and outward open conformations,
based upon the mammalian Glut5 fructose transporter structures, localize Asn411
protruding into the aqueous pathway. This is most prominent when the carrier is
in the inward open conformation when the external gate is closed. Mutations at
this site likely result in highly specific steric and electrostatic interactions
between the Asn411-substituted, and other, residues in the gate region that
impede carrier function. The substrate specificity of the N411K mutant may be due
to alterations of substrate flows through the external gate, downstream
allosteric alterations in the folate-binding pocket, or both.
PMID- 29344586
TI - Systemic multilineage engraftment in mice after in utero transplantation with
human hematopoietic stem cells.
AB - IUHCT of human cord blood-derived CD34+ cells into fetal NSG mice results in
systemic multilineage engraftment with human cells.Preconditioning with in utero
injection of an anti-c-Kit receptor antibody (ACK2) results in an improved rate
of engraftment.
PMID- 29344587
TI - An exploratory study of red raspberry (Rubus idaeus L.) (poly)phenols/metabolites
in human biological samples.
AB - Red raspberry (Rubus idaeus L.) contains a variety of polyphenols including
anthocyanins and ellagitannins. Red raspberry polyphenols absorbed in different
forms (parent compounds, degradants or microbial metabolites) are subject to
xenobiotic metabolism in the intestine, liver, and/or kidney, forming methylate,
glucuronide, and sulfate conjugated metabolites. Upon acute exposure,
(poly)phenol/metabolite presence in the blood depends mainly on intestinal
absorption, enterohepatic circulation, and metabolism by resident microbiota.
However, chronic exposure to red raspberry polyphenols may alter metabolite
patterns depending on adaptions in the xenobiotic machinery and/or microbiota
composition. Understanding the metabolic fate of these compounds and their
composition in different biological specimens relative to the exposure time/dose
will aid in designing future health benefit studies, including the mechanism of
action studies. The present exploratory study applied ultra-high performance
liquid chromatography (UHPLC) coupled with quadrupole time-of-flight (QTOF) and
triple quadrupole (QQQ) mass spectrometries to characterize red raspberry
polyphenols in fruit and then their appearance, including metabolites in human
biological samples (plasma, urine and breast milk) after the chronic intake of
red raspberries. The results suggested that the most abundant polyphenols in red
raspberries included cyanidin 3-O-sophoroside, cyanidin 3-O-glucoside, sanguiin
H6 and lambertianin C. Sixty-two (poly)phenolic compounds were tentatively
identified in the plasma, urine and breast milk samples after the intake of red
raspberries. In general, urine contained the highest content of phenolic
metabolites; phase II metabolites, particularly sulfated conjugates, were mainly
present in urine and breast milk, and breast milk contained fewer parent
anthocyanins compared to urine and plasma.
PMID- 29344588
TI - A helical chain-like organic-inorganic hybrid arsenotungstate with color-tunable
photoluminescence.
AB - A 1-D infinite helical chain-like organic-inorganic hybrid arsenotungstate
Na4H8[{Pr(H2O)2}2{As2W19O68}{WO2(mal)}2].24H2O (mal = malate) (1) was prepared,
which was characterized by elemental analyses, thermogravimetric (TG) analyses,
IR spectroscopy, powder X-ray diffraction (PXRD) and X-ray single-crystal
diffraction. Structural characterization revealed that 1 comprises the organo
functionalized [{As2W19O68}{WO2(mal)}2]18- polyanions hinged together by the Pr3+
ions forming a 1-D infinite helical chain-like architecture. The malate ligand
may play a vital role to stabilize the structure of 1 by the formation of the
five-membered W-O-C-C-O chelate ring. Solid state photoluminescence reveals that
1 features excitation wavelength-dependent emission properties, achieving a
reversible emission color switching simply via changing the excitation
wavelength. Time-resolved emission spectroscopy (TRES) indicates that the
photoexcitation O -> M ligand to metal charge transfer (LMCT) of arsenotungstate
fragments can sensitize the Pr3+ ions through intramolecular energy transitions
in 1.
PMID- 29344589
TI - Magnetism-tuning strategies for graphene oxide based on magnetic oligoacene oxide
patches model.
AB - Graphene oxide (GO) has wide application potential owing to its 2D structure and
diverse modification sites for various targeted uses. The introduction of
magnetism into GO structures has further advanced the controllability of the
application of GO materials. Herein, the concept of modular design and modeling
was applied to tune the magnetism of GO. To obtain desirable magnetic properties,
diradical-structured GO patches were formed by the introduction of two functional
groups to break the Kekule structure of the benzene ring. In these diradical GO
patches, the energy of the triplet state was lower than those of the open-shell
broken-symmetry singlet state and closed-shell singlet state. To create such
multi-radical patches, a practical approach is to determine a substantial spatial
separation of the alpha and beta spin densities in the molecule. Thus, systematic
design strategies and tests were evaluated. The first strategy was extending the
distance between the distribution center of the alpha and beta spin densities;
the second was controlling the delocalization directions of the alpha and beta
electrons; the third was controlling the delocalization extension of the alpha
and beta electrons by oxidative modification, and finally introducing multi
radical structures into the molecular system and controlling the position of each
radical. Herein, successful molecular models with a large magnetic coupling
constant (~3600 cm-1) were obtained. This study paves the way to explore
ferromagnetic MGO guided by theoretical study, which may become reality soon.
PMID- 29344590
TI - Magnetic anisotropy investigation on light lanthanide complexes.
AB - Herein, a series of light lanthanide-based complexes, Ln(fdh)3(bpy) (Ln = CeIII,
PrIII, and NdIII and fdh = 1,1,1-fluoro-5,5-dimethyl-hexa-2,4-dione, bpy = 2,2'
bipyridine), were synthesized and characterized. The angle-resolved magnetometry
studies reveal that the three complexes have Ising-type anisotropy, and the
magnetic easy axes orient along the negative charge dense direction in the
crystal field. The results were consistent with the ab initio calculations. This
research demonstrates that the crystal field electron density distribution
determines the anisotropy of light lanthanides.
PMID- 29344591
TI - Introduction of axial chirality at a spiro carbon atom in the synthesis of
pentaerythritol-imine macrocycles.
AB - Novel chiral macrocyclic polyimines with spiro carbon atoms are described. The
key feature of the synthesis is the formation of an axially chiral quaternary
carbon atom having four constitutionally identical substituents. This is possible
either by the freezing of the labile conformation of a spiro-diboronate moiety or
by the diastereomeric fitting of a conformationally stable spiro-acetal moiety
into a chiral framework. A general model for the description of this type of
axial chirality is proposed.
PMID- 29344592
TI - pH-Responsible fluorescent carbon nanoparticles for tumor selective theranostics
via pH-turn on/off fluorescence and photothermal effect in vivo and in vitro.
AB - We developed nanoparticles comprising a photothermal dye (IR825)-loaded
carbonized zwitterionic polymer [FNP-I] as "switch-on" pH-responsive fluorescence
probes to sense intracellular cancer cells and for near-infrared (NIR)
controllable photothermal therapy (PTT) in vivo and in vitro. The fluorescent
"off" of FNP-I was activated after reaching the cancer cell environment, where
the zwitterionic compartment of FNP lost its hydrophobicity to induce PTT
mediated heat release of IR825 under NIR irradiation in the tumor. Approximately
100% of the IR825 was released from the FNP core to generate high thermal
conversion to completely kill the cancer cells. Furthermore, after intravenous
treatment of FNP-I into MDAMB-231-cell bearing mice, pH-responsive photothermal
therapy was observed, achieving marked ablation of tumor cells with release of
IR825 under tumor environment conditions. In addition, fluorescent signals were
clearly found at the tumor site after 3 h, decreasing at the 6 h time point. The
in vitro and in vivo detection system demonstrated good cellular uptake and
biocompatibility as a potential imaging-guided photothermal therapy nanotool for
cancer treatment. Interestingly, the synergism of the biosensor and PTT in single
FNP-I platform led to more effective cancer cell killing than either monotherapy,
providing a new approach for cancer treatment.
PMID- 29344593
TI - Biologically inspired oxidation catalysis using metallopeptides.
AB - The stereoselective oxidation of hydrocarbons is one of the most challenging
reactions for synthetic chemists. However, this transformation is one of the most
common reactions in nature. Metalloenzymes that catalyze this transformation are
taken as inspiration for the development of new catalysts. There are several
examples in the literature where either peptides or metal catalysts are used in
the stereoselective oxidation reaction, but the synergistic combination of both
systems is still a non-explored field. The use of metallopeptides in biologically
inspired oxidation reactions is discussed in this perspective.
PMID- 29344594
TI - Lithiation of palladated dihydropentacene: a new route for the introduction of
substituents from both of electrophiles and nucleophiles to pentacene.
AB - Dibromodihydropentacene compound 1 was palladated and then lithiated to give a
lithiated-palladated intermediate. Both of the lithium moiety and the palladium
complex moiety on dihydropentacene unexpectedly survived in the solution. The Li
and Pd moieties reacted with electrophiles and nucleophiles respectively to give
the substituted dihydropentacene products. Aromatization of these
dihydropentacenes gave substituted pentacene derivatives.
PMID- 29344595
TI - Quantitative characterization of the ionic mobility and concentration in Li
battery cathodes via low frequency electrochemical strain microscopy.
AB - Electrochemical strain microscopy (ESM) can provide useful information on the
ionic processes in materials at the local scale. This is especially important for
ever growing applications of Li-batteries whose performance is limited by the
intrinsic and extrinsic degradation. However, the ESM method used so far has been
only qualitative due to multiple contributions to the apparent ESM signal. In
this work, we provide a viable approach for the local probing of ionic
concentration and diffusion coefficients based on the frequency dependence of the
ESM signal. A theoretical basis considering the dynamic behavior of ion migration
and relaxation and change of ion concentration profiles under the action of the
electric field of the ESM tip is developed. We argue that several parasitic
contributions to the ESM signal discussed in the literature can be thus
eliminated. The analysis of ESM images using the proposed approach allows a
quantitative mapping of the ionic diffusion coefficients and concentration in
ionic conductors. The results are validated on Li-battery cathodes (LiMn2O4)
extracted from commercial Li-batteries and can provide novel possibilities for
their development and further insight into the mechanisms of their degradation.
PMID- 29344596
TI - Superstructure Ta2O5 mesocrystals derived from (NH4)2Ta2O3F6 mesocrystals with
efficient photocatalytic activity.
AB - Superstructured mesocrystalline Ta2O5 nanosheets were successfully prepared from
mesocrystalline (NH4)2Ta2O3F6 nanorods by the annealing method for the first
time. The as-prepared mesocrystalline Ta2O5 nanosheets in this work showed
remarkable visible light absorption, mainly due to the formation of oxygen
vacancy defects in the mesocrystalline Ta2O5 nanosheets, which was also confirmed
by XPS spectra, Raman spectra and EPR spectra. Besides, the mesocrystalline Ta2O5
nanosheets showed a highly enhanced photocatalytic activity of 11 268.24 MUmol g
1 h-1, about 3.95 times that of commercial Ta2O5. Moreover, the specific surface
area of the mesocrystalline Ta2O5-800 nanosheets was 16.34 m2 g-1, about 5.32
times that of the commercial Ta2O5 (3.072 m2 g-1). The valence band XPS spectra
indicated a strong oxidizing ability of the mesocrystalline Ta2O5 nanosheets in
comparison to that of commercial Ta2O5. The formation of superstructured Ta2O5
mesocrystals generated long lifetime carriers and effective conduction pathways,
which greatly enhanced the photocatalytic activity for hydrogen production.
PMID- 29344597
TI - Rapid localized crystallization of lysozyme by laser trapping.
AB - Confining protein crystallization to a millimetre size was achieved within 0.5 h
after stopping 1 h intense trapping laser irradiation, which shows excellent
performance in spatial and temporal controllability compared to spontaneous
nucleation. A continuous-wave near-infrared laser beam is tightly focused into a
glass/solution interfacial layer of a supersaturated buffer solution of hen egg
white lysozyme (HEWL). The crystallization is not observed during laser trapping,
but initiated by stopping the laser irradiation. The generated crystals are
localized densely in a circular area with a diameter of a few millimetres around
the focal spot and show specific directions of the optical axes of the HEWL
crystals. To interpret this unique crystallization, we propose a mechanism that
nucleation and the subsequent growth take place in a highly concentrated domain
consisting of HEWL liquid-like clusters after turning off laser trapping.
PMID- 29344598
TI - Hot kinetic model as a guide to improve organic photovoltaic materials.
AB - The modeling of organic solar cells (OSCs) can provide a roadmap for their
further improvement. Many OSC models have been proposed in recent years; however,
the impact of the key intermediates from photons to electricity-hot charge
transfer (CT) states-on the OSC efficiency is highly ambiguous. In this study, we
suggest an analytical kinetic model for OSC that considers a two-step charge
generation via hot CT states. This hot kinetic model allowed us to evaluate the
impact of different material parameters on the OSC performance: the driving force
for charge separation, optical bandgap, charge mobility, geminate recombination
rate, thermalization rate, average electron-hole separation distance in the CT
state, dielectric permittivity, reorganization energy and charge delocalization.
In contrast to a widespread trend of lowering the material bandgap, the model
predicts that this approach is only efficient along with improvement of the other
material properties. The most promising ways to increase the OSC performance are
decreasing the reorganization energy, i.e., an energy change accompanying CT from
the donor molecule to the acceptor, increasing the dielectric permittivity and
charge delocalization. The model suggests that there are no fundamental
limitations that can prevent achieving the OSC efficiency above 20%.
PMID- 29344599
TI - Water thermophoresis in carbon nanotubes: the interplay between thermophoretic
and friction forces.
AB - Thermophoresis is the phenomenon wherein particles experience a net drift induced
by a thermal gradient. In this work, molecular dynamics simulations are conducted
to study with atomistic detail the thermophoresis of water nanodroplets inside
carbon nanotubes (CNTs) and its interplay with the retarding liquid-solid
friction. Different applied temperatures, thermal gradients, and droplet sizes
are used to reveal the dynamics of the two kinetic regimes of the thermophoretic
motion in CNTs. The results indicate that during the droplet motion, the
thermophoretic force is independent of the velocity of the droplet, whereas the
magnitude of the retarding friction force exhibits a linear dependence. In fact,
in the initial regime the magnitude of the friction force increases linearly with
the droplet velocity, until the thermophoretic force is balanced by the friction
force as the droplet reaches its terminal velocity in the final regime. In
addition, an increase in the magnitude of the thermophoretic force is found for
longer water droplets. These findings provide a deeper understanding of liquid
transport driven by temperature gradients in nanoconfined geometries where liquid
solid interfaces govern fluidics.
PMID- 29344604
TI - Advancing Clinical Improvements for Patients Using the Theory-Driven and Data
Driven Branches of Computational Psychiatry.
PMID- 29344605
TI - Errors in Tables, Author Affiliation, and Online-Only Supplement.
PMID- 29344606
TI - Errors in Figure and Table 3.
PMID- 29344607
TI - Bosentan for Cutaneous Ulcers in Anti-MDA5 Dermatomyositis.
PMID- 29344608
TI - Nonhealing Crusted Scalp Lesions in a 4-Year-Old Boy.
PMID- 29344609
TI - Generalized Lichen Nitidus Following Anti-PD-1 Antibody Treatment.
PMID- 29344611
TI - Variable Response to Naltrexone in Patients With Hailey-Hailey Disease.
PMID- 29344610
TI - Association of Combined Patterns of Tobacco and Cannabis Use in Adolescence With
Psychotic Experiences.
AB - Importance: There is concern about potentially causal effects of tobacco use on
psychosis, but epidemiological studies have been less robust in attempts to
minimize effects of confounding than studies of cannabis use have been.
Objectives: To examine the association of patterns of cigarette and cannabis use
with preceding and subsequent psychotic experiences, and to compare effects of
confounding across these patterns. Design, Setting, and Participants: This cohort
study used data from the Avon Longitudinal Study of Parents and Children, which
initially consisted of 14 062 children. Data were collected periodically from
September 6, 1990, with collection ongoing, and analyzed from August 8, 2016,
through June 14, 2017. Cigarette and cannabis use data were summarized using
longitudinal latent class analysis to identify longitudinal classes of substance
use. Associations between classes and psychotic experiences at age 18 years were
assessed. Exposures: Depending on the analysis model, exposures were longitudinal
classes of substance use or psychotic experiences at age 12 years. Main Outcomes
and Measures: Logistic regression was used to examine the associations between
substance use longitudinal classes and subsequent onset of psychotic experiences.
Results: Longitudinal classes were derived using 5300 participants (56.1% female)
who had at least 3 measures of cigarette and cannabis use from ages 14 to 19
years. Prior to adjusting for a range of potential confounders, there was strong
evdience that early-onset cigarette-only use (4.3%), early-onset cannabis use
(3.2%), and late-onset cannabis use (11.9%) (but not later-onset cigarette-only
use [14.8%]) latent classes were associated with increased psychotic experiences
compared with nonusers (65.9%) (omnibus P < .001). After adjusting for
confounders, the association for early-onset cigarette-only use attenuated
substantially (unadjusted odds ratio [OR], 3.03; 95% CI, 1.13-8.14; adjusted OR,
1.78; 95% CI, 0.54-5.88), whereas those for early-onset cannabis use (adjusted
OR, 3.70; 95% CI, 1.66-8.25) and late-onset cannabis use (adjusted OR, 2.97; 95%
CI, 1.63-5.40) remained consistent. Conclusions and Relevance: In this study, our
findings indicate that while individuals who use cannabis or cigarettes during
adolescence have an increased risk of subsequent psychotic experiences,
epidemiological evidence is substantively more robust for cannabis use than it is
for tobacco use.
PMID- 29344613
TI - Role of Preoperative Variables in Reducing the Rate of Occult Invasive Disease
for Women Considering Active Surveillance for Ductal Carcinoma In Situ-Reply.
PMID- 29344612
TI - Association of Disease Severity With Skin Microbiome and Filaggrin Gene Mutations
in Adult Atopic Dermatitis.
AB - Importance: Skin microbiome correlates with disease severity for lesional and
nonlesional skin, indicating a global influence of atopic dermatitis (AD). A
relation between skin microbiome and filaggrin gene (FLG) mutations proposes a
possible association between skin microbiome and host genetics. Objectives: To
assess skin and nasal microbiome diversity and composition in patients with AD
and compare with healthy controls, and to investigate the microbiome in relation
to disease severity and FLG mutations in patients with AD. Design, Setting, and
Participants: An observational case-control study of 45 adult healthy controls
and 56 adult patients with AD was carried out from January 2015 to June 2015 in a
tertiary referral center, Department of Dermatology, Bispebjerg Hospital,
Denmark. Exposures: Bacterial swabs were taken from patients with AD (lesional
skin, nonlesional skin, and anterior nares) and from healthy controls
(nonlesional skin and anterior nares). Eczema severity was assessed and FLG
mutations noted. Bacterial DNA was extracted from swabs, and V3-V4 16S rDNA
regions amplified with PCR. Samples were analyzed at Statens Serum Institut
September 2015 to September 2016. Bioinformatics analyses of the microbiome were
analyzed using R statistical software (version 3.3.1, R Foundation Inc). Main
Outcomes and Measures: Skin microbiomes were investigated using next-generation
sequencing targeting 16S ribosomal RNA. Results: Microbiome alpha diversity was
lower in patients with AD compared with healthy controls in nonlesional skin
(effect size, 0.710; 95% CI, 0.27-1.15; P = .002), lesional skin (effect size,
0.728; 95% CI, 0.35-1.33; P = .001), and nose (effect size, 1.111; 95% CI, 0.48
0.94; P < .001). Alpha diversity was inversely correlated with disease severity
for lesional (effect size, 0.530; 95% CI, 0.23-1.64; P = .02) and nonlesional
skin (effect size, 0.451; 95% CI, 0.04-2.44; P = .04) in patients with AD.
Microbiome composition in AD nonlesional skin was linked to FLG mutations.
Conclusions and Relevance: An altered microbiome composition in patients with AD
in nonlesional skin, lesional skin, as well as nose, suggests a global influence
of AD. Microbiome composition in AD nonlesional skin is associated with FLG
mutations, proposing a possible association between the skin microbiome and host
genetics.
PMID- 29344614
TI - Apprehending Otherness Through Wonder: A Facial Plastic Surgeon's Review of the
Book and Movie.
PMID- 29344615
TI - A 30-Year-Old Man With Recurrent Dyspnea and Palpitations.
PMID- 29344616
TI - Ensuring Timely Access to Quality Care for US Veterans.
PMID- 29344617
TI - Eliminating Alcohol-Impaired Driving Fatalities: What Can Be Done?
PMID- 29344618
TI - The Heart-Brain Team-Towards Optimal Team-Based Coordinated Care.
PMID- 29344619
TI - Acoustic Analysis of Voice in Singers: A Systematic Review.
AB - Purpose: Singers are vocal athletes having specific demands from their voice and
require special consideration during voice evaluation. Presently, there is a lack
of standards for acoustic evaluation in them. The aim of the present study was to
systematically review the available literature on the acoustic analysis of voice
in singers. Method: A systematic review of studies on acoustic analysis of voice
in singers (PubMed/MEDLINE, CINAHL, Scopus, ProQuest, Cochrane, Ovid, Science
Direct, and Shodhganga) was carried out. Key words based on PIO (population
investigation-outcome) were used to develop search strings. Titles and abstracts
were screened independently, and appropriate studies were read in full for data
extraction. Results: Of the 895 studies, 26 studies met the inclusion criteria.
Great variability was noted in the instruments and task used. Different acoustic
measures were employed, such as fundamental frequency, perturbation, cepstral,
spectral, dysphonia severity index, singing power ratio, and so forth.
Conclusion: Overall, a great heterogeneity was noted regarding population, tasks,
instruments, and parameters. There is a lack of standardized criteria for the
evaluation of singing voice. In order to implement acoustic analysis as a part of
comprehensive voice evaluation exclusively for singers, there is a certain need
for methodical sound studies.
PMID- 29344621
TI - Role of Preoperative Variables in Reducing the Rate of Occult Invasive Disease
for Women Considering Active Surveillance for Ductal Carcinoma In Situ.
PMID- 29344620
TI - Association of Depression With Mortality in Older Adults Undergoing Transcatheter
or Surgical Aortic Valve Replacement.
AB - Importance: Depression is increasingly recognized as a risk factor for adverse
outcomes in cardiovascular disease. However, little is known about depression in
older adults undergoing transcatheter (TAVR) or surgical (SAVR) aortic valve
replacement. Objective: To determine the prevalence of depression and its
association with all-cause mortality in older adults undergoing TAVR or SAVR.
Design, Setting, and Participants: This preplanned analysis of the Frailty Aortic
Valve Replacement (FRAILTY-AVR) prospective cohort study included 14 centers in 3
countries from November 15, 2011, through April 7, 2016. Individuals 70 years or
older who underwent TAVR or SAVR were enrolled. Depressive symptoms were
evaluated using the Geriatric Depression Scale Short Form at baseline and follow
up. Main Outcomes and Measures: All-cause mortality at 1 and 12 months after TAVR
or SAVR. Logistic regression was used to determine the association of depression
with mortality after adjusting for confounders such as frailty and cognitive
impairment. Results: Among 1035 older adults (427 men [41.3%] and 608 women
[58.7%]) with a mean (SD) age of 81.4 (6.1) years, 326 (31.5%) had a positive
result of screening for depression, whereas only 89 (8.6%) had depression
documented in their clinical record. After adjusting for clinical and geriatric
confounders, baseline depression was found to be associated with mortality at 1
month (odds ratio [OR], 2.20; 95% CI, 1.18-4.10) and at 12 months (OR, 1.532; 95%
CI, 1.03-2.24). Persistent depression, defined as baseline depression that was
still present 6 months after the procedure, was associated with a 3-fold increase
in mortality at 12 months (OR, 2.98; 95% CI, 1.08-8.20). Conclusions and
Relevance: One in 3 older adults undergoing TAVR or SAVR had depressive symptoms
at baseline and a higher risk of short-term and midterm mortality. Patients with
persistent depressive symptoms at follow-up had the highest risk of mortality.
PMID- 29344622
TI - Barriers to and Facilitators of Implementing Enhanced Recovery Pathways Using an
Implementation Framework: A Systematic Review.
PMID- 29344625
TI - Perception of Cantonese Lexical Tones by Pediatric Cochlear Implant Users.
AB - Purpose: The purpose of this study is to assess Cantonese word recognition and
the discrimination of Cantonese tones with manipulated contours by child and
adolescent cochlear implant (CI) users and a group of peers with normal hearing
(NH). It was hypothesized that the CI users would perform more poorly than their
counterparts with NH in both tasks and that CI users implanted before 2 years of
age would perform better than those implanted after 2 years. Method: Forty-one
participants were recruited from hospitals, schools, and kindergartens in Hong
Kong: Ten CI users implanted at or before 2 years of age ("early" CI group), 13
CI users implanted after 2 years of age ("late" CI group), and 18 individuals
with NH. The mean age at implantation of the early CI group was 1.5 years (SD =
0.3), and for the late CI group, it was 4.3 years (SD = 2.1). Participants were a
mean of 13.3 years of age (SD = 3.7) at time of testing. Participants completed a
Cantonese word recognition test and a discrimination task using Cantonese tones
with modified fundamental frequency trajectories. Results: Both CI user groups
obtained significantly lower scores than the group with NH on the word
recognition test. Mean percent correct scores for the word recognition test were
79% for the early CI group, 69% for the late CI group, and 97% for the group with
NH. The group with NH consistently achieved higher scores than the CI user groups
when discriminating manipulated Cantonese tones. Increasing the acoustic
difference between tones improved discrimination performance for CI users for
level tone contrasts only. CI users implanted at or before 2 years of age
obtained higher scores than those implanted later. Conclusions: The results of
this study add further evidence that children using CIs do not perform as well as
peers in perceiving Cantonese tones. Modification of tones to increase pitch
range did not consistently improve the ability of children with implants to
perceive the difference between tones. Further research is required to fully
assess potential benefits of early implantation for speakers of tonal languages.
Supplemental Materials: https://doi.org/10.23641/asha.5782209.
PMID- 29344627
TI - Error in Author Affiliations.
PMID- 29344626
TI - Is Depression an Important New Mortality Risk Factor After Aortic Valve
Replacement or Simply a Component of the Geriatric Disease Spectrum?
PMID- 29344628
TI - Errors in Abstract, Text, and Figure 1 and Addition of Open Access.
PMID- 29344631
TI - A Brief Exposure-Based Treatment vs Cognitive Processing Therapy for
Posttraumatic Stress Disorder: A Randomized Noninferiority Clinical Trial.
AB - Importance: Written exposure therapy (WET), a 5-session intervention, has been
shown to efficaciously treat posttraumatic stress disorder (PTSD). However, this
treatment has not yet been directly compared with a first-line PTSD treatment
such as cognitive processing therapy (CPT). Objective: To determine if WET is
noninferior to CPT in patients with PTSD. Design, Setting, and Participants: In
this randomized clinical trial conducted at a Veterans Affairs medical facility
between February 28, 2013, and November 6, 2016, 126 veteran and nonveteran
adults were randomized to either WET or CPT. Inclusion criteria were a primary
diagnosis of PTSD and stable medication therapy. Exclusion criteria included
current psychotherapy for PTSD, high risk of suicide, diagnosis of psychosis, and
unstable bipolar illness. Analysis was performed on an intent-to-treat basis.
Interventions: Participants assigned to CPT (n = 63) received 12 sessions and
participants assigned to WET (n = 63) received 5 sessions. The CPT protocol that
includes written accounts was delivered individually in 60-minute weekly
sessions. The first WET session requires 60 minutes while the remaining 4
sessions require 40 minutes. Main Outcomes and Measures: The primary outcome was
the total score on the Clinician-Administered PTSD Scale for DSM-5;
noninferiority was defined by a score of 10 points. Blinded evaluations were
conducted at baseline and 6, 12, 24, and 36 weeks after the first treatment
session. Treatment dropout was also examined. Results: For the 126 participants
(66 men and 60 women; mean [SD] age, 43.9 [14.6] years), improvements in PTSD
symptoms in the WET condition were noninferior to improvements in the CPT
condition at each of the assessment periods. The largest difference between
treatments was observed at the 24-week assessment (mean difference, 4.31 points;
95% CI, -1.37 to 9.99). There were significantly fewer dropouts in the WET vs CPT
condition (4 [6.4%] vs 25 [39.7%]; chi21 = 12.84, Cramer V = 0.40). Conclusions
and Relevance: Although WET involves fewer sessions, it was noninferior to CPT in
reducing symptoms of PTSD. The findings suggest that WET is an efficacious and
efficient PTSD treatment that may reduce attrition and transcend previously
observed barriers to PTSD treatment for both patients and providers. Trial
Registration: clinicaltrials.gov Identifier: NCT01800773.
PMID- 29344632
TI - Factors Associated With Outcomes and Costs After Pediatric Laparoscopic
Cholecystectomy.
AB - Importance: The prevalence of pediatric cholelithiasis is increasing with the
epidemic of childhood obesity. With this rise, the outcomes and costs of
pediatric laparoscopic cholecystectomy become an important public health and
economic concern. Objective: To assess patient and health system factors
associated with the outcomes and costs after laparoscopic cholecystectomy among
Canadian children. Design, Setting, and Participants: This was a retrospective,
population-based study of children 17 years and younger undergoing laparoscopic
cholecystectomy from April 1, 2008, until March 31, 2015. The data source was the
Canadian Institute for Health Information. The Canadian Institute for Health
Information Discharge Abstract Database includes data from all Canadian
hospitals. The analysis was limited to inpatient cholecystectomies. All Canadian
children undergoing laparoscopic cholecystectomy were included. Exposure: The
exposure in this study was laparoscopic cholecystectomy. Main Outcomes and
Measures: The primary outcome was all-cause morbidity, a composite outcome of any
complication that prolonged length of stay by 24 hours or required a second,
unplanned procedure. The cost of the index admission was also calculated as a
secondary outcome. These outcomes of interest were determined before data
analysis. Odds ratios and 95% CIs were estimated using multilevel logistic
regression models. Results: During the study period, 3519 laparoscopic
cholecystectomies were performed; of these, 79.1% (n = 2785) were in girls, and
98.0% (n = 3450) were for gallstone disease. The overall morbidity rate was 3.9%
(n = 137). After adjustment, patients with comorbidities were more susceptible to
morbidity (odds ratio, 2.68; 95% CI, 1.78-3.86; P < .001). Operations for
gallstones were less morbid. High-volume general surgeons had lower morbidity
rates compared with low-volume pediatric surgeons (odds ratio, 0.32; 95% CI, 0.12
0.69; P = .005) independent of pediatric volumes. The mean (SD) unadjusted cost
of a laparoscopic cholecystectomy was $4115 ($7273). Operative indication,
complications, comorbidities, emergency admission, and surgeon volume were
associated with cost. Conclusions and Relevance: The high-volume nature of adult
general surgery translated to lower morbidity and cost after pediatric
laparoscopic cholecystectomy, suggesting that adult volume is associated with
pediatric outcomes. As the rate of pediatric gallstone disease increases, surgeon
volume, rather than specialty training, should be considered when pursuing
operative management.
PMID- 29344633
TI - Considering the Ability of General Surgeons to Add Value to Pediatric Surgery.
PMID- 29344634
TI - Underlying mechanism of the photodynamic activity of hematoporphyrin-induced
apoptosis in U87 glioma cells.
AB - Photodynamic therapy (PDT) is a relatively novel type of tumor therapy method
with low toxicity and limited side-effects. The aim of the present study was to
investigate the underlying mechanism and potential microRNAs (miRNAs) involved in
the treatment of glioma by PDT with hematoporphyrin, a clinical photosensitizer.
The photodynamic activity of hematoporphyrin on the cell viability and apoptosis
of gliomas was investigated by MTT, and flow cytometry and fluorescence
microscopy, respectively. Alterations in singlet oxygen and mitochondrial
membrane potential were detected. The differentially expressed miRNAs and
proteins were evaluated by miRNA gene chip and apoptosis-associated protein chip,
respectively. The results demonstrated that cell viability significantly
decreased with hematoporphyrin concentration. PDT with hematoporphyrin
significantly increased cell apoptosis at a later stage, induced the content of
reactive oxygen species (ROS) and decreased the mitochondrial membrane potential,
indicating that PDT with hematoporphyrin inhibited cell growth via induction of
radical oxygen, decreased the mitochondrial membrane potential and induced
apoptosis. The upregulated miRNAs, including hsa-miR-7641, hsa-miR-9500, hsa-miR
4459, hsa-miR-21-5p, hsa-miR-663a and hsa-miR-205-5p may be important in PDT
induced cell apoptosis in glioma. Transporter 1, ATP binding cassette subfamily B
member- and nuclear factor-kappaB-mediated apoptosis signaling pathways were the
most significant pathways. Thus, the current study presents PDT as a potential
therapeutic approach for the treatment of malignant glioma, and identified miRNAs
for the molecular design and development of a third-generation photosensitizer
(PS).
PMID- 29344635
TI - Eradication of cervical cancer in vivo by an AAV vector that encodes shRNA
targeting human papillomavirus type 16 E6/E7.
AB - The major causative agent of cervical cancer is human papilloma virus (HPV); the
viral proteins E6 and E7 induce carcinogenesis through the inactivation of the
host tumor-suppressor gene. Therefore, the stable expression of specific
inhibitors of E6 and E7 in cancer cells is expected to provide effective
treatment for cervical cancer without affecting normal tissue. In this study, we
propose a novel therapeutic approach using an adeno-associated virus (AAV) vector
encoding short hairpin RNA (shRNA) against the oncoproteins E6 and E7 (shE6E7) of
HPV type 16 (HPV-16), termed AAV-shE6E7. Three different HPV-16-positive cervical
cancer cell lines (BOKU, SiHa and SKG-IIIa cells) were tested for gene transfer
efficiency using serotypes of AAV vectors. For in vitro analysis, the cells were
transduced AAV-shE6E7; alternatively, in vivo studies were performed via the
administration of a direct injection of AAV-shE6E7 into cervical cancer cell
derived tumors in mice. The high gene transfer efficiency was observed using AAV2
in all three cervical cancer cell lines. Following transduction, we observed
apoptosis, G1 phase arrest and cell growth inhibition. Additionally, in the
transduced cells, the E6, E7 and p16 expression levels decreased, whereas the
expression levels of p53, p21 and pRb levels were enhanced. The growth of
subcutaneously transplanted tumors was markedly inhibited by the single
administration of AAV2-shE6E7, and the tumors were almost completely eradicated
without any adverse effects. These results provided evidence of the utility of
AAV2-shE6E7 as a novel treatment approach for cervical cancer.
PMID- 29344636
TI - Analysis of the prolonged infusion of DFP-10917, a deoxycytidine analog, as a
therapeutic strategy for the treatment of human tumor xenografts in vivo.
AB - 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentofranocyl-cytosine (DFP-10917, CNDAC) is
a 2'-deoxycytidine analog with antitumor activity against various tumor cells.
However, a clinically available therapeutic regimen for this compound needs to be
established and its functional mechanisms in relation to the dosing schedule need
to be clarified. In this study, we evaluated the antitumor activity and toxicity
of DFP-10917 by varying the dose and administration schedule in human solid tumor
and leukemia xenografts in vivo. Compared to a 1-day infusion with a high-dose of
DFP-10917 (30 mg/kg/day), a prolonged 14-day infusion with a low-dose (4.5
mg/kg/day) exerted superior tumor growth inhibitory effects without decreasing
the body weights of mice in our human tumor xenograft model. In addition, we
found that a 14-day infusion of low-dose DFP-10917 markedly prolonged the
lifespan of nude mice bearing both acute leukemia and ovarian cancer cell-derived
tumors. On the other hand, gemcitabine (GEM) and cytosine arabinoside (Ara-C),
which are similar deoxycytidine analogs and are widely used clinically as
standard regimens, exerted less potent antitumor effects than DFP-10917 on these
tumors. To elucidate the possible functional mechanisms of the prolonged infusion
of DFP-10197 compared with that of GEM or Ara-C, the rate of DNA damage in CCRF
CEM and HeLa cells treated with DFP-10917, Ara-C and GEM was detected using a
comet assay. DFP-10917, at a range of 0.05 to 1 uM, induced a clear tailed-DNA
pattern in both the CCRF-CEM and HeLa cells; Ara-C and GEM did not have any
effect. It was thus suggested that a low concentration and long-term exposure to
DFP-10917 aggressively introduced the fragmentation of DNA molecules, namely the
so-called double-strand breaks in tumor cells, leading to potent cytotoxicity.
Moreover, treatment with DFP-10917 at a low-dose with a long-term exposure
specifically increased the population of cells in the G2/M phase, while GEM
reduced this cell population, suggesting a unique function (G2/M arrest) of DFP
10917. On the whole, our findings indicate that the prolonged infusion of low
dose DFP-10917 mainly displays a novel functional mechanism as a DNA-damaging
drug and may thus prove to be useful in the treatment of cancer patients who are
resistant to other cytosine nucleosides, or in patients in which these other
nucleosides have been shown to be ineffective.
PMID- 29344637
TI - miR-186, a serum microRNA, induces endothelial cell apoptosis by targeting SMAD6
in Kawasaki disease.
AB - Kawasaki disease (KD) is an acute, self-limited vasculitis that predominantly
affects medium-sized arteries, particularly the coronary arteries. Recent studies
have indicated that microRNAs are involved in many diseases, including KD.
However, the detailed mechanism remains unclear. The aim of the present study was
to explore the role of miR-186 in KD and potentially discover a new target for KD
treatment. The results demonstrated that miR-186 was upregulated in serum from
patients with KD and KD serum could increase miR-186 transcript levels in
endothelial cells (HUVECs). Overexpression of miR-186 mimic induced HUVEC
apoptosis through mitogen-activated protein kinase (MAPK) activation by targeting
and inhibiting SMAD family member 6 (SMAD6). Furthermore, KD serum induced HUVEC
apoptosis through miR-186. In conclusion, the present results suggested that KD
serum-associated miR-186 has an essential role in endothelial cell apoptosis by
activating the MAPK pathway through targeting the SMAD6 gene.
PMID- 29344638
TI - Garcinone C exerts antitumor activity by modulating the expression of
ATR/Stat3/4E-BP1 in nasopharyngeal carcinoma cells.
AB - Nasopharyngeal carcinoma (NPC) is one of the most common head and neck
malignancies and is typically treated with radiotherapy and chemotherapy.
Garcinone C, a natural compound isolated from Garcinia oblongifolia Champ., is a
xanthone derivative with potential cytotoxic effects on certain cancers. However,
there are limited studies regarding its effects on NPC cells, and its mechanism
of action in NPC remains unknown. In the present study, we found that garcinone C
significantly inhibited cell viability of the human NPC cell lines CNE1, CNE2,
HK1 and HONE1. This inhibition was exerted in a time- and dose-dependent manner.
Flow cytometry demonstrated that garcinone C arrested the cell cycle at the S
phase. Moreover, with 10 uM of high-dose garcinone C treatment, the cells
exhibited necrotic morphology changes including cell swelling, rough endoplasmic
reticulum degranulation, endoplasmic reticulum dilatation, mitochondrial swelling
and vacuolar degeneration. In addition, we found that garcinone C stimulated the
expression levels of ATR and 4E-BP1, while efficiently inhibiting the expression
levels of cyclin B1, cyclin D1, cyclin E2, cdc2, CDK7 and Stat3. Collectively,
the ability of garcinone C to inhibit NPC in growth in vitro suggested that
garcinone C may be a novel agent for the management of NPC.
PMID- 29344639
TI - Therapeutic potential of a dual mTORC1/2 inhibitor for the prevention of
posterior capsule opacification: An in vitro study.
AB - Mammalian target of rapamycin (mTOR) serves a central role in regulating cell
growth and survival, and has been demonstrated to be involved in the pathological
progression of posterior capsule opacification (PCO). In the present study, the
potency of PP242, a novel dual inhibitor of mTOR complex 1/2 (mTORC1/2), in the
suppression of the growth of human lens epithelial cells (HLECs) was
investigated. Using a Cell Counting Kit-8 and a wound healing assay, it was
demonstrated that PP242 inhibited the proliferation and migration of HLECs. In
addition, western blot analysis indicated that PP242 completely inhibited mTORC1
and mTORC2 downstream signaling activities, whereas rapamycin only partially
inhibited mTORC1 activity within LECs. Furthermore, PP242 treatment led to an
upregulation of the expression levels of p53 and B cell lymphoma-2 (Bcl-2)
associated X and downregulation of Bcl-2. In addition, flow cytometric analysis
demonstrated that PP242 induced the cell cycle arrest at the G0/G1 phase, which
may have caused apoptosis and induced autophagy within the LECs. The results of
the present study suggested that administration of PP242 may potentially offer a
novel therapeutic approach for the prevention of PCO.
PMID- 29344640
TI - Over-regulation of microRNA-133b inhibits cell proliferation of cisplatin-induced
non-small cell lung cancer cells through PI3K/Akt and JAK2/STAT3 signaling
pathway by targeting EGFR.
AB - The present study determined the anticancer activity and its mechanism of
microRNA-133b on cell proliferation of cisplatin-induced non-small cell lung
cancer cells. The expression of microRNA-133b cisplatin-induced non-small cell
lung cancer (NSCLC) tissue was lower than that of para-carcinoma tissue in
patients. Overall survival of higher expression in cisplatin-induced NSCLC
patients was higher than that of lower expression in cisplatin-induced NSCLC
patients. Over-regulation of microRNA-133b inhibited cell proliferation and LDH
activity, induced apoptosis and caspase-3 activity, suppressed the protein
expression of EGFR, PI3K, p-Akt, p-JAK2 and p-STAT3, decreased cyclin D1 and
increased Bax protein expression in cisplatin-induced A549 cells. EGFR inhibitor
(lapatinib) suppressed EGFR protein expression, inhibited cell proliferation and
LDH activity, and induced apoptosis and caspase-3 activity in cisplatin-induced
A549 cells by over-regulation of microRNA-133b. When EGFR protein expression was
suppressed, PI3K, p-Akt, p-JAK2 and p-STAT3, decreased cyclin D1 and increased
Bax protein expression in cisplatin-induced A549 cells by over-regulation of
microRNA-133b. Altogether, our results indicated that over-regulation of microRNA
133b inhibits cell proliferation of cisplatin-induced NSCLC by PI3K/Akt and
JAK2/STAT3 signaling pathway by targeting EGFR.
PMID- 29344641
TI - Inhibition of RPTOR overcomes resistance to EGFR inhibition in triple-negative
breast cancer cells.
AB - Triple-negative breast cancer (TNBC) cells frequently exhibit activated growth
factor signaling and resistance to inhibitors for epidermal growth factor
receptor (EGFR), despite the overexpression of EGFR protein, and this is
associated with a malignant behavior and a poor prognosis. In this study, to
elucidate the underlying mechanisms of resistance to EGFR inhibitor and identify
inhibitors that exert a synergistic effect with EGFR inhibition, we examined the
inhibitory effects of selected protein kinase inhibitors (PKIs) in combination
with gefitinib on the viability of a mesenchymal stem-like (MSL) subtype TNBC
cell line. MK-2206, an AKT inhibitor, and a group of mammalian target of
rapamycin (mTOR) inhibitors were found to exert synergistic lethal effects in
combination with gefitinib in MDA-MB-231 cells. The combination of gefitinib/MK
2206 exerted a prominent synergistic lethal effect in an MTT cell viability assay
and a growth inhibitory effect in a long-term colony-forming assay in 2 MSL
subtype TNBC cell lines (MDA-MB-231 and HS578T) and one basal-like (BL) subtype
TNBC cell line (MDA-MB-468). Gefitinib/MK-2206 treatment synergistically
decreased the mTOR signaling target substrates along with the downregulation of
ribosomal protein S6 (RPS6), a marker of cell proliferation and target substrate
of the AKT-mTOR signaling pathway. In addition, gefitinib markedly reduced the
viability of MDA-MD-231 and HS578T cells when regulatory-associated protein of
mTOR (RPTOR) was suppressed by siRNA-based knockdown (KD). These results thus
suggest that RPTOR mediates, at least partially, the resistance to EGFR
inhibition in TNBC cells. Therefore, targeting the mTOR complex 1 (mTORC1)
pathway may be a potential strategy for the treatment of EGFR-resistant TNBC.
PMID- 29344642
TI - Microarray analysis reveals Tmub1 as a cell cycle-associated protein in rat
hepatocytes.
AB - Transmembrane and ubiquitin-like domain containing protein 1 (Tmub1), formerly
known as hepatocyte odd protein shuttling (HOPS) has been recognized as a
ubiquitously expressed shuttling protein that moves between the nucleus and
cytoplasm in hepatocytes. Tmub1 is involved in liver regeneration and functions
as a bridging protein in tumor cell proliferation. To investigate the
transcriptional profile and potential biological processes affected by Tmub1
expression in normal rat hepatocytes, microarray and bioinformatics experiments
were used to identify 127 mRNAs differentially expressed between Tmub1
overexpression, Tmub1-knockdown and normal BRL-3A cells (fold-change >=2.5). The
expression levels of 17 key node genes associated with the cell cycle were
confirmed by reverse transcription-quantitative polymerase chain reaction
analysis. Flow cytometry, 5-Ethynyl-20-deoxyuridine, Cell Counting Kit-8 and
western blotting experiments revealed the effects on the cell cycle and the
inhibition of proliferation in BRL-3A cells overexpressing Tmub1. Further co
immunoprecipitation assays demonstrated that Tmub1 interacts with cyclin A2
during the cell cycle and that the overexpression of Tmub1 may postpone cyclin A2
and cyclin B1 degradation in the M phase. The results of the present study
indicated that Tmub1 functions as a cell proliferation inhibitor and cell cycle
associated protein.
PMID- 29344643
TI - MicroRNA-23a-5p regulates osteogenic differentiation of human bone marrow-derived
mesenchymal stem cells by targeting mitogen-activated protein kinase-13.
AB - The molecular mechanisms of osteogenic differentiation of bone marrow-derived
mesenchymal stem cells (BMSCs) remain to be fully elucidated. MicroRNAs (miRs)
serve vital roles in the process of regulating osteogenic differentiation of
BMSCs. The present study aimed to investigate the role of miR-23a-5p in
osteogenic differentiation of human (h)BMSCs, and the underlying molecular
mechanism. The results of reverse transcription-quantitative polymerase chain
reaction demonstrated that miR-23a-5p was significantly downregulated in the
process of osteogenic differentiation. Upregulation of miR-23a-5p inhibited
osteogenic differentiation of hBMSCs, and down-regulated expression of miR-23a-5p
enhanced this process, which was confirmed by alkaline phosphatase (ALP) and
Alizarin Red S staining. A dual-luciferase reporter assay confirmed that mitogen
activated protein kinase 13 (MAPK13) was a direct target of miR-23a-5p. In
addition, knockdown of MAPK13 inhibited osteogenic differentiation of hBMSCs,
similar to the effect of upregulation of miR-23a-5p. Finally, the knockdown of
MAPK13 also blocked the effect of miR-23a-5p in osteogenic differentiation of
hBMSCs, which was also confirmed by ALP and Alizarin Red S staining. These
results indicated that by targeting MAPK13, miR-23a-5p serves a vital role in
osteogenic differentiation of hBMSCs, which may provide novel clinical treatments
for bone injury however, further studies are required.
PMID- 29344645
TI - Targeted disruption of adenosine kinase in myeloid monocyte cells increases
osteoclastogenesis and bone resorption in mice.
AB - Adenosine kinase (ADK) serves an important role in intracellular adenosine
clearance via phosphorylating adenosine to AMP. The role of adenosine and its
receptors in the maintenance of bone homeostasis is well studied, particularly in
osteoclastogenesis and bone resorption; however, the function of ADK in bone
metabolism is still unclear. In the present study, utilizing the cre/floxp
recombination system, mice with conditional loss of ADK function in myeloid
monocyte cells were used to assess the effect of ADK deficiency on bone
metabolism. Mice were evaluated by means of gross observation and bone
histomorphometric analysis. Ex vivo osteoclast differentiation and bone
resorption were also examined using genetic deletion and pharmacologic inhibition
of ADK in osteoclasts. Compared with control mice, the results of the present
study demonstrate that adult mice lacking ADK in the myeloid monocyte cells had
reduced body weight and nasoanal length. The results of bone histomorphometric
analysis revealed that bone mass was significantly decreased and osteoclastic
parameters were increased in the study mice. Furthermore, in vitro cell culture
revealed that inhibition of ADK function promoted osteoclast differentiation and
bone resorption. Osteoclast-associated gene expression, including tartrate
resistant acid phosphatase, nuclear factor of activated T-cells, cytoplasmic 1,
matrix metalloproteinase 9, Cathepsin K and calcitonin receptor, was also
significantly increased. These results suggest that mice with ADK deficiency have
reduced bone formation due to increased osteoclastogenesis and bone resorption.
The present study provides further insight into the mechanism by which ADK serves
a key role in bone metabolism.
PMID- 29344646
TI - Engineered zinc-finger transcription factors inhibit the replication and
transcription of HBV in vitro and in vivo.
AB - In the present study, an artificial zinc-finger transcription factor eukaryotic
expression vector specifically recognizing and binding to the hepatitis B virus
(HBV) enhancer (Enh) was constructed, which inhibited the replication and
expression of HBV DNA. The HBV EnhI-specific pcDNA3.1-artificial transcription
factor (ATF) vector was successfully constructed, and then transformed or
injected into HepG2.2.15 cells and HBV transgenic mice, respectively. The results
demonstrated that the HBV EnhI (1,070-1,234 bp)-specific ATF significantly
inhibited the replication and transcription of HBV DNA in vivo and in vitro. The
HBV EnhI-specific ATF may be a meritorious component of progressive combination
therapies for eliminating HBV DNA in infected patients. A radical cure for
chronic HBV infection may become feasible by using this bioengineering
technology.
PMID- 29344644
TI - Inactivation of DNA-PK by knockdown DNA-PKcs or NU7441 impairs non-homologous end
joining of radiation-induced double strand break repair.
AB - The DNA-dependent protein kinase (DNA-PK) complex plays a pivotal role in non
homologous end-joining (NHEJ) repair. We investigated the mechanism of NU7441, a
highly selective DNA-PK inhibitor, in NHEJ-competent mouse embryonic fibroblast
(MEF) cells and NHEJ-deficient cells and explored the feasibility of its
application in radiosensitizing nasopharyngeal carcinoma (NPC) cells. We
generated wild-type and DNA-PKcs-/- MEF cells. Clonogenic survival assays, flow
cytometry, and immunoblotting were performed to study the effect of NU7441 on
survival, cell cycle, and DNA repair. NU7441 profoundly radiosensitized wild-type
MEF cells and SUNE-1 cells, but not DNA-PKcs-/- MEF cells. NU7441 significantly
suppressed radiation-induced DSB repair post-irradiation through unrepaired and
lethal DNA damage, the cell cycle arrest. The effect was associated with the
activation of cell cycle checkpoints. The present study revealed a mechanism by
which inhibition of DNA-PK sensitizes cells to irradiation suggesting that
radiotherapy in combination with DNA-PK inhibitor is a promising paradigm for the
management of NPC which merits further investigation.
PMID- 29344647
TI - Autophagy regulates the degeneration of the auditory cortex through the AMPK-mTOR
ULK1 signaling pathway.
AB - Presbycusis is the most common sensory impairment associated with aging; however,
the underlying molecular mechanism remains unclear. Autophagy has been
demonstrated to serve a key role in diverse diseases; however, no studies have
examined its function in central presbycusis. The aim of the present study was to
investigate the changes of autophagy in the physiological processes of the
auditory cortex and its role in the degeneration of the auditory cortex, as well
as the related mechanisms using naturally aging rats and a D-galactose (D-gal)
induced mimetic rat model of aging. The present study demonstrated that autophagy
increased from 3 months to 15 months in the normal saline (NS) control group,
while it decreased in the D-gal group. Compared with the age-matched NS group,
the D-gal group demonstrated significantly increased levels of the autophagy
related proteins, LC3 and Beclin 1 (BECN1) and the anti-apoptotic proteins B-cell
lymphoma (BCL)2 and BCL-extra large (BCL-xL) at 3 months, with no obvious changes
in cell apoptosis level and neuron ultrastructural morphology. However, LC3,
BECN1, BCL2 and BCL-xL were decreased at 15 months in the D-gal group, with cell
apoptosis significantly increased and substantial neuron degeneration.
Additionally, 5' AMP-activated protein kinase (AMPK) activity was enhanced, and
mechanistic target of rapamycin (mTOR) and ULK1 phosphorylation (Ser 757)
activities were inhibited at 3 months compared with those of the NS group, while
the opposite was observed at 9 and 15 months. The present results suggested that
autophagy increases from young to adult and decreases at old age in the
physiological processes of the auditory cortex, and has anti-apoptotic as well as
anti-aging functions in the degeneration of the auditory cortex. Additionally,
autophagy was regulated through AMPK activation and mTOR suppression, and
impairment of autophagy may serve a key role in the degeneration of the auditory
cortex, even in the pathogenesis of central presbycusis.
PMID- 29344648
TI - Effect of midkine on gemcitabine resistance in biliary tract cancer.
AB - Gemcitabine-based chemotherapy is one of the most effective and commonly used
chemotherapeutic regimens for biliary tract cancer (BTC). However, development of
resistance to this drug limits its efficacy. The present study aimed to explore
the effects of midkine (MDK) on the resistance of BTC cells to gemcitabine. Cell
viability and proliferation were measured by a Cell Counting Kit-8 assay and 5
ethynyl-2'-deoxyuridine staining, respectively. Western blot analysis was used to
detect the expression of E-cadherin and vimentin. The results indicated that BTC
cell lines were more resistant to gemcitabine plus MDK compared with gemcitabine
alone. In terms of the underlying mechanism, MDK promoted the epithelial to
mesenchymal transition (EMT) of BTC cells and the enhancing effect of MDK on
gemcitabine resistance was abrogated when the EMT was blocked with small
interfering (si)RNA targeting Twist. In addition, MDK promoted the expression of
Notch-1, while knockdown of Notch-1 by siRNA blocked the EMT process in the BTC
cell lines. Taken together, these results indicated that MDK promoted gemcitabine
resistance of BTC through inducing EMT via upregulating Notch-1. It was suggested
that inhibition of the EMT is a promising strategy to overcome MDK-induced drug
resistance.
PMID- 29344649
TI - Effects of intrathecal bupivacaine on the NR2B/CaMKIIalpha/CREB signaling pathway
in the rat lumbar spinal cord.
AB - Neuraxial anesthesia produces an anesthetic-sparing, sedative effect. The
mechanism underlying this effect potentially involves decreased spinal afferent
input. However, the neurochemical mechanisms at the spinal level remain unknown.
The N-methyl-D-aspartate receptor 2B subunit/calcium-calmodulin-dependent protein
kinase II alpha/cAMP response element-binding protein (NR2B/CaMKIIalpha/CREB)
signaling pathway serves an important role in regulating the transmittance of
peripheral noxious stimulation to supraspinal regions in the process of
nociception. The present study investigated the effects of intrathecal
bupivacaine on the NR2B/CaMKIIalpha/CREB signaling pathway. Following
catheterization, 36 male Sprague-Dawley rats were randomly assigned to a normal
saline (NS) or bupivacaine treatment group, in which each rat intrathecally
received 20 ul normal saline or 0.5% bupivacaine, respectively. The expression
levels of NR2B, CaMKIIalpha/p-CaMKIIalpha, and CREB/phosphorylated (p)-CREB in
the lumbar spinal cord were investigated by western blotting, reverse
transcription-quantitative polymerase chain reaction and immunohistochemistry
(IHC). Following bupivacaine treatment, western blot analysis demonstrated that
the protein expression levels of NR2B, p-CaMKIIalpha, and p-CREB in the spinal
cord were reduced by approximately 54, 56 and 33%, respectively, compared with NS
control rats. Similar alterations in expression were observed by IHC analysis.
Additionally, mRNA expression levels of NR2B, CaMKIIalpha, and CREB were also
downregulated following the intrathecal administration of bupivacaine. Therefore,
the sedative effect of subarachnoid blockade with bupivacaine possibly occurs
through de-afferentation, which may reduce cortical arousal by downregulating the
spinal NR2B/CaMKIIalpha/CREB pathway in vivo, however further investigation is
required in order to verify this.
PMID- 29344650
TI - Adrenomedullin serves a role in the humoral pathway of delayed remote ischemic
preconditioning via a hypoxia-inducible factor-1alpha-associated mechanism.
AB - Remote ischemic preconditioning (RIPC) is a minimally invasive method that
provides protection by reducing injury to the heart, kidneys, brain and other
tissues or organs. RIPC may improve the outcome in patients undergoing surgery.
Although the role of RIPC has been studied, the results remain controversial. It
is difficult to confirm whether RIPC has a kidney protective effect and the
understanding of the preconditioning signal pathway involved remains unclear. In
the present study, the effect of RIPC in urology was evaluated. The protection
against renal damage was assessed by investigating the potential mediator,
hypoxia-inducible factor-1alpha (HIF-1alpha), and the functional adrenomedullin
(ADM) pathway. Male Sprague-Dawley (SD) rats were used in the present study. The
animal model of kidney damage induced by ischemia reperfusion (IR) was used to
investigate the protective effect of the acute and delayed phase RIPC.
Furthermore, the protective effects of RIPC mediated by a HIF-1alpha-ADM pathway
were assessed. The indexes of renal function and oxidative damage indicators were
measured by Cr, BUN, mALB, beta2-MG, MPO, MDA and SOD assays, and the expression
of HIF-1alpha and ADM were detected by western blot analysis,
immunohistochemistry and ELISA assays. Tubular score, determined using
hematoxylin and eosin staining, was used to evaluate renal tissue damage.
Applying RIPC prevented IR-induced renal dysfunction and oxidative damage by
decreasing Cr, BUN, mALB, beta2-MG, MPO, MDA levels and increasing SOD activity.
Findings showed that delayed RIPC had an improved effect compared with acute
treatment. Delayed RIPC also upregulated the expression of HIF-1alpha and ADM,
indicating that the protective effect of the delayed RIPC may be associated with
a HIF-1alpha-ADM-mediated mechanism. The effect of the delayed RIPC to reduce IR
induced renal damage and increase ADM expression was enhanced by HIF-1alpha
agonists DMOG and BAY 85-3934, whereas the effect was whittled by HIF-1alpha
antagonists YC-1 and 2-MeOE2. Furthermore, receiving ADM also offered protection
to the kidney in comparison with the IR+Vehicle group. These findings suggest
that RIPC prevents IR-mediated renal damage by HIF-1alpha via an ADM humoral
pathway. In the present study, RIPC provided an effective renal protection. ADM
could also offer protection regulated by HIF-1alpha in renal tissue. However, the
mechanism of ADM as a protective factor in RIPC requires further research.
PMID- 29344651
TI - Identification of genes and pathways in the synovia of women with osteoarthritis
by bioinformatics analysis.
AB - Osteoarthritis (OA) has a high prevalence in female patients and sex may be a key
factor affecting the progression of OA. The aim of the present study was to
identify genetic signatures in the synovial membranes of female patients with OA
and to elucidate the potential associated molecular mechanisms. The gene
expression profiles of the GSE55457 and GSE55584 datasets were obtained from the
Gene Expression Omnibus database. Data of two synovial membranes from normal
female individuals (GSM1337306 and GSM1337310) and two synovial membranes from
female patients affected by OA (GSM1337327 and GSM1337330) were obtained from the
dataset GSE55457, and those of three synovial membranes from female patients
affected by OA (GSM1339628, GSM1339629 and GSM1339632) were obtained from the
dataset GSE55584. Differentially expressed genes (DEGs) were identified by using
Morpheus software. Protein-protein interaction (PPI) networks of the DEGs were
constructed by using Cytoscape software. Subsequently, Gene Ontology (GO)
function and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment
analyses of the top module of the PPI network were performed by using ClueGo. A
total of 377 DEGs were identified in the synovial membranes of OA patients
compared with those of normal individuals, including 164 upregulated and 213
downregulated genes. The top 10 hub genes were ubiquitin (UB)C, ribosomal protein
(RP) L23A, mammalian target of rapamycin, heat shock protein 90 alpha family
class A member 1, RPS28, RPL37A, RPS24, RPS4X, RPS18 and UBB. The results of the
GO analysis indicated that the DEGs included in the top module of the PPI were
mainly enriched in the terms 'nuclear-transcribed mRNA catabolic process',
'nonsense mediated decay', and 'cytoplasmic translation and ribosomal small
subunit biogenesis'. KEGG pathway analysis indicated that the DEGs included in
the top one module were mainly enriched in the 'ribosome' pathway. The present
study provides a systematic, molecular-level understanding of the degeneration of
the synovial membrane in the progression of OA in female patients. The hub genes
and molecules associated with the synovial membrane may be used as biomarkers and
therapeutic targets for the treatment of OA in female patients with OA.
PMID- 29344652
TI - Chrysophanol inhibits proliferation and induces apoptosis through NF
kappaB/cyclin D1 and NF-kappaB/Bcl-2 signaling cascade in breast cancer cell
lines.
AB - Chrysophanol is an anthraquinone compound, which exhibits anticancer effects on
certain types of cancer cells. However, the effects of chrysophanol on human
breast cancer remain to be elucidated. The aim of the present study was to
clarify the role of chrysophanol on breast cancer cell lines MCF-7 and MDA-MB
231, and to identify the signal transduction pathways regulated by chrysophanol.
MTT assay and flow cytometric analysis demonstrated that chrysophanol inhibited
cell proliferation, and cell cycle progression in a dose-dependent manner. The
expression of cell cycle-associated cyclin D1 and cyclin E were downregulated
while p27 expression was upregulated following chrysophanol treatment at the
mRNA, and protein levels. The Annexin V/propidium iodide staining assay results
revealed that apoptosis levels increased following chrysophanol treatment.
Chrysophanol upregulated caspase 3 and poly (ADP-ribose) polymerase cleavage in
both cell lines. Furthermore, chrysophanol enhanced the effect of paclitaxel on
breast cancer cell apoptosis. In addition, chrysophanol downregulated apoptosis
regulator Bcl-2 protein, and transcription factor p65 and IkappaB
phosphorylation. Inhbition of nuclear factor (NF)-kappaB by ammonium pyrrolidine
dithiocarbamate diminished the effect of chrysophanol on apoptosis and associated
proteins. In conclusion, the results of the current study demonstrated that
chrysophanol effectively suppresses breast cancer cell proliferation and
facilitates chemosentivity through modulation of the NF-kappaB signaling pathway.
PMID- 29344653
TI - A novel variant of osteogenesis imperfecta type IV and low serum phosphorus level
caused by a Val94Asp mutation in COL1A1.
AB - Osteogenesis imperfecta (OI) is a rare congenital disorder characterized by bone
fragility and fractures, and associated with bone deformity, short stature,
dentin, ligament and blue-gray eye sclera. OI is caused by a heterozygous
mutation in collagen alpha-1(I) chain (COL1A1) or collagen alpha-2(I) chain
(COL1A2) genes that encode alpha chains of type I collagen. Collagen alpha chain
peptide contains an N-propeptide, which has a role in assembly and processing of
collagen. Point mutations in the N-propeptide domain appear to trigger OI. In the
present study, a novel heterozygous missense mutation, c.281T>A (p.Val94Asp), was
identified in the von Willebrand C domain of N-terminal of type I collagen in an
individual with type IV OI. The majority of N-terminal mutations are associated
with OI/Ehlers-Danlos syndrome (EDS); however, in the present study, the affected
individual did not suffer from EDS and the level of serum phosphorus of the
patient was low (0.67 mmol/l). A number of clinical phenotypes were observed at
the same variation site or in the same region on the polypeptide chain of COL1A,
which suggests that additional genetic and environmental factors may influence
the severity of OI. The present study may provide insight into the phenotype
genotype association in collagen-associated diseases and improve clinical
diagnosis of OI.
PMID- 29344654
TI - Tunicamycin inhibits colon carcinoma growth and aggressiveness via modulation of
the ERK-JNK-mediated AKT/mTOR signaling pathway.
AB - Epidemiology and evidence have demonstrated that colon carcinoma is one of the
most common gastrointestinal tumors in the clinic. Reports have suggested that
Tunicamycin significantly inhibits aggressiveness of colon carcinoma cells by
promotion of apoptosis. In the present study, the inhibitory effect of
tunicamycin on colon cancer cells and the potential underlying molecular
mechanism was investigated. Western blotting, immunohistochemistry, apoptotic
assays and immunofluorescence were used to analyze the therapeutic effects of
tunicamycin on apoptosis, growth, aggressiveness and cell cycle of colon tumor
cells, by downregulation of fibronectin, vimentin and E-cadherin expression
levels. In vitro experiments demonstrated that tunicamycin significantly
inhibited growth, migration and invasion of colon carcinoma cells. In addition,
tunicamycin administration promoted apoptosis of colon carcinoma cells via
upregulation of apoptotic protease activating factor 1 and cytochrome c
expression levels, which are proteins that have a role in mitochondrial apoptosis
signaling. Cell cycle assays revealed that tunicamycin suppressed proliferation
and arrested S phase entry of colon carcinoma cells. Mechanistic analysis
demonstrated that tunicamycin reduced expression and phosphorylation levels of
extracellular signal-regulated kinase (ERK), c-JUN N-terminal kinase (JNK) and
protein kinase B (AKT), and inhibited mammalian target of rapamycin (mTOR)
expression levels in colon carcinoma cells. Endogenous overexpression of ERK
inhibited tunicamycin-mediated downregulation of JNK, AKT and mTOR expression,
which further blocked tunicamycin-mediated inhibition of growth and
aggressiveness of colon carcinoma. In vivo assays revealed that tunicamycin
treatment significantly inhibited tumor growth and promoted apoptosis, which led
to long-term survival of tumor-bearing mice compared with the control group. In
conclusion, these results suggested that tunicamycin may inhibit growth and
aggressiveness of colon cancer via the ERK-JNK-mediated AKT/mTOR signaling
pathway, and suggested that tunicamycin may be a potential anti-cancer agent for
colon carcinoma therapy.
PMID- 29344655
TI - Protective effects of osthole against inflammation induced by lipopolysaccharide
in BV2 cells.
AB - Inflammation and oxidative stress are implicated in the development of
neurodegenerative diseases. Osthole is a compound that is extracted from She
Chuang Zi, which is a type of traditional Chinese medicine. Osthole has
previously been demonstrated to exhibit anticancer activities and has a low
toxicity. However, to the best of our knowledge, the anti-inflammatory effects of
osthole in microglial cells have not been investigated extensively. The aim of
the present study was to investigate the potential protective effects of osthole
against inflammation induced by lipopolysaccharide (LPS) in microglial cells. The
present study employed LPS-stimulated BV2 mouse microglia to establish an
inflammatory cell model and to investigate the anti-inflammatory effects of
osthole. Cells were pretreated with osthole for 1 h prior to LPS (10 ug/ml)
stimulation. At 6 h after the addition of LPS, alterations in the levels of
inflammatory factors, including tumor necrosis factor (TNF)-alpha, interleukin
(IL)-6 and IL-1beta, were determined by ELISA. Furthermore, at 24 h after the
addition of LPS, western blot analysis was performed to analyze the alterations
in the protein expression of nuclear factor-kappaB (NF-kappaB) p65,
phosphorylated-NF-kappaB p65, nuclear factor erythroid 2-related factor 2 (Nrf2)
and heme oxygenase (HO)-1. The results demonstrated that the secretion of the
inflammatory cytokines TNF-alpha, IL-6 and IL-1beta by LPS-stimulated BV2 cells
was significantly reduced by osthole treatment. Simultaneously, osthole treatment
inhibited the LPS-induced activation of the NF-kappaB signaling pathway. In
addition, osthole upregulated the expression of Nrf2 and HO-1 in a dose-dependent
manner. Based on these results, osthole may exhibit anti-inflammatory effects via
the NF-kappaB and Nrf2 pathways, indicating that osthole has the potential to be
developed into an effective anti-inflammatory drug.
PMID- 29344656
TI - Liraglutide suppresses proliferation and induces adipogenic differentiation of
3T3-L1 cells via the Hippo-YAP signaling pathway.
AB - Liraglutide, as a glucagon-like peptide-1 analogue, is used to treat type 2
diabetes mellitus and obesity. Previous findings have demonstrated the effects of
liraglutide on adipogenesis; however, the underlying mechanism involved in this
process remains to be elucidated. In the present study, to certify the effect of
liraglutide on adipogenesis and explore the possible underlying mechanism
involved in this process, preadipocyte 3T3-L1 cells were cultured in adipocyte
inducing medium and treated with liraglutide. Subsequently, the expression levels
of the master transcription factors and adipocyte-specific genes were measured by
reverse transcription-quantitative polymerase chain reaction and immunoblotting
analysis. Lipid droplet production was detected by Oil red O staining. Cell
proliferation was determined by a Cell Counting Kit-8 assay and cell
immunofluorescence for Ki67, and apoptosis was assessed by flow cytometry. Next,
the expression levels of the core components in the Hippo-yes-associated protein
(YAP) signaling pathway as well as YAP-specific target genes were measured.
Finally, short interfering RNAs of mammalian ste20 kinase 1/2 (MST1/2), a key
protein kinase in the Hippo-YAP pathway, were used to determine whether
liraglutide regulated adipogenic differentiation via the Hippo-YAP pathway. It
was demonstrated that liraglutide promoted adipogenic differentiation, suppressed
proliferation, did not affect apoptosis of 3T3-L1 cells and activated the Hippo
YAP signaling pathway at the initial stage of adipogenesis. Silencing of MST1
counteracted the effect of increasing adipogenesis by liraglutide. These results
suggested that liraglutide may activate the Hippo-YAP signaling pathway leading
to the inhibition of proliferation of preadipocyte 3T3-L1 cells, and result in
cells achieving transformation into mature adipocytes sooner. Taken together, the
results of the present study may expand knowledge of the underlying mechanism of
liraglutide facilitating adipogenesis, and may contribute to the development of
GLP-1 receptor agonists for weight loss and increased insulin sensitivity.
PMID- 29344657
TI - Effects of hereditary moderate high fat diet on metabolic performance and
physical endurance capacity in C57BL/6 offspring.
AB - Obesity in pregnant women presents a risk to fetal health, leading to numerous
metabolic syndromes and chronic inflammation risks. Previously, physical exercise
was considered to be one of the primary treatments for obesity. However, the
effect of fat consumption throughout the life cycle on physical endurance
capacity remains unknown. A total of two groups of female mice (age, 6 weeks;
C57BL/6J) were fed with a normal chow diet and a moderate high fat diet (MHFD),
during pregnancy and lactation (8 weeks), with the offspring receiving the same
diet as the mother. When filial mice were 8, 16 and 24 weeks old, they were
tested for endurance, blood pressure (BP) and glucose tolerance, as well as
adipose tissue infiltration and macrophage subtype. Compared with the control
group, filial mice in MHFD groups exhibited increased BP and glucose levels and
larger adipose cells (~4-fold). During adolescence, the obese filial mice
demonstrated increased endurance compared with controls. Endurance declines in
middle and old age; the endurance of aged obese mice was 29% that of lean ones.
In addition, body coordination and movement memory did not notably change. The
expression of cluster of differentiation 68, one of the most reliable markers of
macrophages, increased by 2.48-fold, demonstrating that macrophages were
recruited and underwent infiltration. In addition, increased tumor necrosis
factor-alpha and decreased interleukin-10 expression demonstrated that
infiltrated macrophages are polarized to the M1 state, which weakens physical
endurance and resists type M2 macrophages, which exhibit repairing functions. In
conclusion, hereditary MHFD weakens physical endurance and alters the metabolic
characteristics of C57BL/6 offspring.
PMID- 29344658
TI - MicroRNA-188-3p is involved in sevoflurane anesthesia-induced neuroapoptosis by
targeting MDM2.
AB - Sevoflurane is a commonly used inhalation anesthetic. Sevoflurane-induced
neuroapoptosis and cognitive impairments in animals are widely reported, however,
the underlying molecular mechanisms remain largely unknown. The results of the
present study demonstrated that sevoflurane anesthesia induced spatial memory
impairments in rats, as determined by the Morris water maze test.
Mechanistically, the current study demonstrated that sevoflurane administration
significantly enhanced the expression of microRNA (miR)-188-3p. Furthermore,
inhibition of miR-188-3p using lentiviral miR-188-3p inhibitors attenuated
sevoflurane-induced cognitive impairments in rats. The present study also
demonstrated that miR-188-3p targeted MDM2 proto-oncogene (MDM2) and negatively
regulated the expression of MDM2, as determined by luciferase assays, reverse
transcription-quantitative polymerase chain reaction and western blot analysis.
Furthermore, decreased abundance of MDM2 following transfection with miR-188-3p
mimics was associated with increased stability of p53 protein. Suppression of p53
activity using the specific p53 inhibitor pifithrin-alpha alleviated sevoflurane
induced neuroapoptosis. These results indicate that the miR-188-3p-MDM2-p53 axis
may have a critical role in sevoflurane-induced cognitive dysfunction. Therefore,
miR-188-3p may be a potential target for the treatment of sevoflurane-induced
cognitive impairment.
PMID- 29344659
TI - Degree of endplate chondrocyte degeneration in different tension regions during
mechanical stimulation.
AB - The aim of this study was to explore the degree of degeneration of endplate
chondrocytes in different tension regions induced by intermittent cyclic
mechanical tension (ICMT) in vitro. Rat endplate chondrocytes were harvested and
treated with 10% ICMT for 8 h/day with a frequency of 0.5 Hz. A cartilage
degeneration model was induced using an FX-5000T cell strain-loading system. The
experiment was divided into the central region and the peripheral region,
according to the contact area between the loading post and the six-well flexible
silicone rubber BioFlex plates. Toluidine blue and phalloidin staining were used
to observe the morphological changes of cells following mechanical stimulation.
Apoptosis was detected by flow cytometry and the mRNA and protein expression
levels of collagen type II alpha1, aggrecan, SRY-box 9 and matrix
metalloproteinase 13 were detected by reverse transcription-quantitative
polymerase chain reaction (RT-qPCR) and western blotting, respectively. Endplate
chondrocytes exhibited degenerative alterations under mechanical conditions of
10% ICMT and 0.5 Hz at 8 h/day. Toluidine blue and phalloidin staining
demonstrated that the cells in the peripheral region were more slender compared
with cells in the central region, but RT-qPCR and western blotting results
demonstrated that the degree of cell degeneration between the two groups was not
statistically differences. So that cell morphological alteration does not imply
that cells have undergone degeneration.
PMID- 29344660
TI - Purple sweet potato color attenuates high fat-induced neuroinflammation in mouse
brain by inhibiting MAPK and NF-kappaB activation.
AB - Purple sweet potato color (PSPC) is a natural anthocyanin pigment that is derived
from purple sweet potato storage roots. PSPC possesses a variety of biological
activities, including antioxidant, anti-inflammatory and neuroprotective effects;
however, the detailed effects of PSPC on high-fat diet (HFD)-induced
neuroinflammation remain to be determined. The aim of the present study was to
investigate whether PSPC has a protective role in HFD-associated
neuroinflammation in the mouse brain and to provide novel insight into the
mechanisms of the action. C57BL 6J mice were maintained on a normal diet (10
kcal% fat), a HFD (60 kcal% fat), a HFD with PSPC (700 mg/kg/day) or PSPC alone,
which was administrated over 20 weeks. Open field and step-through tests were
used to evaluate the effects of HFD and PSPC on mouse behavior and memory
function. Western blotting and ELISA analyses were used to assess the expression
of inflammatory cytokines and the activation of mitogen-activated protein kinase
and nuclear factor-kappaB (NF-kappaB). The results demonstrated that PSPC
treatment was able to significantly improve the HFD-induced impairment of mouse
behavior and memory function, and suppressed the increase in body weight, fat
content, hyperlipemia and the level of endotoxin. PSPC treatment also markedly
decreased the expression of cyclooxygenase-2, inducible nitric oxide synthase,
tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-6, and increased the
level of IL-10 in the HFD-treated mouse brain. In addition, PSPC inhibited the
HFD-induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun
N-terminal kinase (JNK) and p38, and the activation of NF-kappaB. These findings
indicated that PSPC treatment may alleviate HFD-induced neuroinflammation in the
mouse brain by inhibiting ERK, JNK, p38 and NF-kappaB activation.
PMID- 29344661
TI - Plasma levels of microRNA-21, -126 and -423-5p alter during clinical improvement
and are associated with the prognosis of acute heart failure.
AB - MicroRNAs are associated with myocardial damage and heart failure (HF). The
present study investigated whether the plasma levels of microRNA (miR)-21, -126
and -423-5p alter according to the (de)compensated state of patients with HF and
are associated with all-cause mortality. In 48 patients with HF admitted to the
emergency room for an episode of acute decompensation, blood samples were
collected to measure miR and B-type natriuretic peptide levels within 24 h of
hospital admission, at the time of hospital discharge, and a number of weeks post
discharge (chronic stable compensated state). Levels of miR-21, miR-126 and miR
423-5p increased between admission and discharge, and decreased following
clinical compensation. During follow-up (up to 48 months), 38 patients (79%) were
rehospitalized at least once and 21 patients (44%) succumbed. Patients who had
increased levels of miR-21 and miR-126 at the time of clinical compensation
exhibited better 24-month survival and remained rehospitalization-free for a
longer period compared with those with low levels. Additionally, patients whose
levels of miR-423-5p increased between admission and clinical compensation
experienced fewer hospital readmissions in the 24 months following the time of
clinical compensation compared with those who had decreased levels. It was
concluded that the plasma levels of miR-21, miR-126 and miR-423-5p altered during
clinical improvement and were associated with the prognosis of acute
decompensated HF.
PMID- 29344662
TI - Dengue virus-1 NS5 genetic variant associated with a severe clinical infection:
Possible reduction of the innate immune response by inhibition of interferon type
1 and the Janus kinase-signal transducer and activator of transcription signaling
pathway.
AB - Dengue virus (DENV) is currently considered as one of the most important mosquito
borne viral pathogens affecting humans. Genetic variations in viruses are likely
to be a condition for more effective evasion of the immune system and resulting
in severe clinical consequences. The DENV-1 NS5 gene was sequenced to establish
whether during an epidemic burst there were genetic variations of the virus and
whether any variant was associated (through a case-control design) with severe
clinical behavior. A total of 31 patients positive for DENV-1 were enrolled.
Among the nucleotide differences between the sequences, only two generated amino
acid changes. The variants 124Met/166Ser (amino acid positions according to the
report GenBank AJL35015.1), were associated with a severe clinical course of the
disease. Via in silico tests, it was identified that the variations generate
changes in the protein probably affecting the function of type-1 interferon,
either at the level of its receptor or by interfering with the Janus kinase
signal transducer and activator of transcription signaling pathway.
PMID- 29344663
TI - Adeno-associated virus type 2-mediated gene transfer of a short hairpin-RNA
targeting human IGFBP-2 suppresses the proliferation and invasion of MDA-MB-468
cells.
AB - Adeno-associated virus 2 (AAV2) is prepotent in the biological treatment of
breast tumor because of its low pathogenicity and immunogenicity. Our previous
study demonstrated that insulin-like growth factor-binding protein 2 (IGFBP-2)
was highly expressed in patients with breast metastasis. In the present study,
the effects of recombinant AAV2 on the growth and metastasis of breast cancer
cells were determined in vitro, and in vivo. rAAV2-ZsGreen-shRNA-scramble and
rAAV2-ZsGreen-shRNA-hIGFBP-2 were used to transfect MDA-MB-468, and MCF-10A cells
respectively, and observed that these virus could not penetrate the normal human
breast epithelia MCF-10A cell line. To investigate the effect of the recombinant
virus on chemotherapeutics, paclitaxel was added to MDA-MB-468 cells and it was
demonstrated that rAAV2-ZsGreen-shRNA-hIGFBP-2-infected MDA-MB-468 cells were
highly chemosensitive to paclitaxel compared with rAAV2-ZsGreen-shRNA-scramble
injected cells. In addition, it was demonstrated that the invasive ability of
rAAV2-ZsGreen-shRNA-hIGFBP-2-infected MDA-MB-468 cells was highly impaired
compared with the rAAV2-ZsGreen-shRNA-scramble group. In the nude mice
xenografts, the rAAV2-ZsGreen-shRNA-hIGFBP-2 injection inhibited tumor growth and
Ki-67 expression was significantly downregulated compared with the scramble
group. Following IGFBP-2 knockdown using rAAV2-ZsGreen-shRNA-hIGFBP-2, matrix
metalloproteinase-2 expression was significantly reduced in tumor tissues
compared with that in rAAV2-ZsGreen-shRNA-scramble treated tumor tissues. These
findings have provided a direction for the application of novel AAV2-based
therapeutics for treating aggressive triple-negative breast cancer types.
PMID- 29344665
TI - Overexpression of septin-7 inhibits melatonin-induced cell apoptosis in human
fetal osteoblastic cells via suppression of endoplasmic reticulum stress.
AB - Our previous study demonstrated that melatonin could induce apoptosis in the
human fetal osteoblastic (hFOB) 1.19 cell line via induction of endoplasmic
reticulum stress (ERS), and recent studies have demonstrated that the expression
of septin-7 (SEPT7) exhibits a positive correlation with the concentration of
melatonin. Western blotting demonstrated the expression level of SEPT7 was
significantly upregulated in a dose-dependent manner following treatment with
differing concentrations of melatonin compared with the control groups, which did
not receive any treatment. The expression of proteins associated with cell
apoptosis and endoplasmic reticulum stress (ERS; pro-caspase-3, cleaved caspase
3, C/EBP-homologous protein, 78 kDa glucose-regulated protein and phosphorylated
eukaryotic translation initiation factor 2alpha) were decreased following
transfection with SEPT7 overexpression plasmid and increased following
transfection with SEPT7 small interfering RNA compared with the control groups.
The results of the present study suggest that SEPT7 inhibits melatonin-induced
cell apoptosis via suppression of ERS.
PMID- 29344664
TI - Crucial role of OX40/OX40L signaling in a murine model of asthma.
AB - The aim of the present study was to explore the roles of OX40/OX40 ligand (OX40L)
signaling and OX40+ T cells in ovalbumin (OVA)-induced mouse asthma model. Asthma
was induced by OVA exposure and subsequent co-treatment with OX40L protein,
neutralizing anti-OX40L blocking antibody, OX40+ T cells or PBS. The protein
expression levels of interleukin (IL)-4, IL-6, IL-13, IL-17, tumor necrosis
factor (TNF)-alpha and interferon (IFN)-gamma in bronchoalveolar lavage fluid
(BALF) were examined using murine cytokine-specific ELISA. Eosinophil
accumulation as well as proliferation and apoptosis of T cells in BALF were
detected by Cell Counting kit-8 and flow cytometric assays. Expression of the
apoptosis-related protein cleaved caspase-3 was examined in OX40+ T cells using
western blot assay. Flow cytometric analysis revealed that OVA-treated mice that
were co-treated with OX40L or OX40+ T cells exhibited higher eosinophil
infiltration compared with control mice treated only with OVA, whereas
neutralizing anti-OX40L blocking antibody inhibited eosinophil infiltration.
ELISA assays demonstrated that the expression of IL-4, IL-6, IL-13, IL-17, TNF
alpha and IFN-gamma in BALF in OX40L-treated and OX40+ T cell-treated mice was
increased compared with expression levels in control mice. Treatment with OX40L
protein effectively reduced apoptosis of T cells and the expression of cleaved
caspase-3 in T cells. OX40L-treated and OX40+ T cell-treated mice exhibited
increased asthma through OX40/OX40L signaling, which probably promoted
inflammatory factor expression, eosinophil infiltration and T cell proliferation.
PMID- 29344666
TI - Let-7b regulates alpaca hair growth by downregulating ectodysplasin A.
AB - Hypohidrotic ectodermal dysplasia (HED), also known as anhidrotic ectodermal
dysplasia, is characterized by the clinical manifestations of less sweat or no
sweat, sparse or no hair, tooth agenesis and/or abnormal tooth morphology. The
characteristics of alpaca ear hair differ from the back hair. The ectodysplasin A
(EDA) signaling pathway has a regulatory effect on skin development and hair
growth. The aim of the present study was to study the effects of EDA on alpaca
hair growth by examining the mRNA and protein expression levels of EDA in alpaca
ear and back skin by reverse transcription-quantitative polymerase chain reaction
and western blot analysis, respectively. Results indicated that EDA expression
was higher in the ear skin compared with the back skin. The expression levels of
let-7b in the skin of healthy alpacas varies; the difference between let-7b
expression levels of the ear and back have been reported to be >2-fold,
suggesting a role for let-7b in the development of adult alpaca skin and hair
follicles. A dual-luciferase reporter vector was constructed to verify the
targeting relationship between microRNA let-7b and EDA, and the results revealed
that EDA was a target gene of let-7b. Alpaca skin fibroblasts were transfected
with a let-7b eukaryotic expression vector to investigate the regulatory
relationship between let-7b and EDA. The expression of EDA was decreased in the
transfected group; immunocytochemical results demonstrated that the EDA protein
was abundantly expressed in the fibroblast cytoplasm. EDA protein expression was
weaker in the transfected cells than in the untransfected cells. These results
suggested that EDA may serve a role in alpaca hair growth and is probably a
target gene of let-7b; let-7b downregulated EDA mRNA and protein expressions,
which suggested that let-7b may regulate alpaca hair growth. These conclusions
suggested that let-7b may be associated with HED.
PMID- 29344667
TI - Clinical evaluation of covered stents in the treatment of superficial femoral
artery pseudoaneurysm in drug abusers.
AB - The present study aimed to investigate the technical feasibility and initial
clinical outcomes of a covered stent for the endovascular treatment of
superficial femoral artery (SFA) pseudoaneurysm in drug abusers. A total of 29
drug abuse patients with SFA pseudoaneurysm, as confirmed by color Doppler
sonography, were enrolled to the present study between January 2012 and May 2014.
All patients were treated percutaneously by implantation of a covered stent.
Physical examination and lower extremity computed tomography angiography were
performed at 1 and 9 months postoperation. Furthermore, the ankle-brachial index
(ABI) of all patients was measured. The results indicated that placement of the
covered stent was technically successful in all 29 patients. All of the ruptured
pseudoaneurysms were successfully sealed with no cases of intraprocedural
mortality. In addition, all patients' conditions improved rapidly; active
hemorrhage subsidence and vascular bruit disappearance were immediately detected
following implantation of the covered stent. During the follow-up period, pain
was markedly alleviated and pulsatile mass was decreased as time increased. No
complaints or complications were documented. A total of 9 months postoperation,
pain and pulsatile mass were not detected. The patency rate of the stent was
100%, and no migration, occlusion or infection was detected. In addition, the ABI
was significantly improved, from 0.52+/-0.09 to 0.97+/-0.37 (P<0.01). In
conclusion, the placement of a covered stent may be considered a promising
approach to provide an effective, safe and minimally invasive option for the
treatment of SFA pseudoaneurysm in drug abusers.
PMID- 29344668
TI - Blocking of autocrine IGF-1 reduces viability of human umbilical cord mesenchymal
stem cells via inhibition of the Akt/Gsk-3beta signaling pathway.
AB - Human umbilical cord mesenchymal stem cells (hUCMSCs) are able to secrete growth
factors, such as hepatocyte growth factor, vascular endothelial growth factor and
insulin-like growth factor-1 (IGF-1). The secretion of these growth factors by
transplanted hUCMSCs have been identified to stimulate the growth of the host
cells in the target organs or tissues. The aim of the present study was to
investigate the effect of autocrine IGF-1 on cell viability of hUCMSCs. The
expression levels of IGF-1 and the IGF-1 receptor (IGF-1R) in hUCMSCs were
identified using immunocytochemistry staining. In order to block autocrine IGF-1,
hUCMSCs were treated with 5 ug/ml alphaIR-3, a specific IGF-1R antibody, for 24
h. The cells cultured in medium without alphaIR-3 were used as the control group.
Cell viability, apoptosis, cell cycle and the proliferation-associated proteins
were quantified using an MTT assay, flow cytometry and western blotting. The
findings of the present study revealed that IGF-1 and IGF-1R were positively
expressed in hUCMSCs. Treatment with alphaIR-3 significantly reduced cell
viability and increased apoptosis of hUCMSCs (P<0.01). Cell cycle analysis
indicated that the number of cells in the G2/M phase was reduced in the alphaIR-3
treated group compared with the control group. Western blotting revealed that the
expression levels of phosphorylated (p)-protein kinase B (Akt), p-glycogen
synthase kinase 3beta (GSK-3beta), p-p70 S6 kinase and cyclin D1 were markedly
reduced and p21 expression was markedly increased in the alphaIR-3-treated group
as compared with the control group (P<0.05). However, no significant difference
was identified in the p-extracellular-signal regulated kinase 1/2 expression when
the alphaIR-3 treatment group was compared with the control group. (P>0.05). The
findings of the present study suggested that the autocrine IGF-1 from hUCMSCs may
be capable of influencing cell viability of hUCMSCs, which may be associated with
activation of Akt/GSK-3beta signaling pathway.
PMID- 29344669
TI - CLC-2 is a positive modulator of oligodendrocyte precursor cell differentiation
and myelination.
AB - Oligodendrocytes (OLs) are myelin-forming cells that are present within the
central nervous system. Impaired oligodendrocyte precursor cell (OPC)
differentiation into mature OLs is a major cause of demyelination diseases.
Therefore, identifying the underlying molecular mechanisms of OPC differentiation
is crucial to understand the processes of myelination and demyelination. It has
been acknowledged that various extrinsic and intrinsic factors are involved in
the control of OPC differentiation; however, the function of ion channels,
particularly the voltage-gated chloride channel (CLC), in OPC differentiation and
myelination are not fully understood. The present study demonstrated that CLC-2
may be a positive modulator of OPC differentiation and myelination. Western
blotting results revealed that CLC-2 was expressed in both OPCs and OLs.
Furthermore, CLC-2 currents (ICLC-2) were recorded in both types of cells. The
inhibition of ICLC-2 by GaTx2, a blocker of CLC-2, was demonstrated to be higher
in OPCs compared with OLs, indicating that CLC-2 may serve a role in OL
differentiation. The results of western blotting and immunofluorescence staining
also demonstrated that the expression levels of myelin basic protein were reduced
following GaTx2 treatment, indicating that the differentiation of OPCs into OLs
was inhibited following CLC-2 inhibition. In addition, following western blot
analysis, it was also demonstrated that the protein expression of the myelin
proteins yin yang 1, myelin regulatory factor, Smad-interacting protein 1 and sex
determining region Y-box 10 were regulated by CLC-2 inhibition. Taken together,
the results of the present study indicate that CLC-2 may be a positive regulator
of OPC differentiation and able to contribute to myelin formation and repair in
myelin-associated diseases by controlling the number and open state of CLC-2
channels.
PMID- 29344670
TI - PGC-1alpha ameliorates kidney fibrosis in mice with diabetic kidney disease
through an antioxidative mechanism.
AB - The production of reactive oxygen species (ROS) is a common phenomenon in
podocyte impairment, which leads to the irreversible progression of chronic
kidney diseases, such as diabetic kidney disease (DKD). Previous research has
indicated that peroxisome proliferator-activated receptor gamma (PPARgamma)
coactivator-1alpha (PGC-1alpha) participates in mitochondrial biogenesis and
energy metabolism in certain mitochondria-enriched cells, including myocardial
and skeletal muscle cells. Therefore, we hypothesized that PGC-1alpha may be a
protective nuclear factor against energy and oxidative stress in DKD. To
investigate this hypothesis, db/db diabetic mice were used to establish a DKD
model and the PPARgamma agonist rosiglitazone was employed to induce PGC-1alpha
expression in vivo. Additionally, immortalized mouse podocytes and SV40 MES 13
renal mesangial cells were utilized for in vitro experiments. The expression
levels of PGC-1alpha and genes associated with kidney and cell injury were
determined by western blotting or reverse transcription-quantitative polymerase
chain reaction and intracellular ROS levels were assessed by 2',7'
dichlorodihydrofluorescein diacetate. The results of the present study
demonstrated that endogenous PGC-1alpha expression exhibited protective effects
against oxidative stress, glomerulosclerosis and tubulointerstitial fibrosis in
experimental DKD. These results indicated a potential role of PGC-1alpha in the
amelioration of key pathophysiological features of DKD and provided evidence for
PGC-1alpha as a potential therapeutic target in DKD.
PMID- 29344671
TI - Role of miR-34c in the cognitive function of epileptic rats induced by
pentylenetetrazol.
AB - Studies suggest that microRNA (miR)-34c may serve a role in cognitive function in
rodent and primate groups. A previous study demonstrated an increase in miR-34c
expression in chronic epileptic rats with memory disorders, induced by
pentylenetetrazol (PTZ). However, the mechanism underlying the effects of miR-34c
on cognitive function in epileptic rats remains unclear. Therefore, the present
study investigated alterations in cognitive function in temporal lobe epileptic
rats, induced by repeated injections of PTZ, following treatment with an miR-34c
agomir compared with a scramble group. Increased expression of miR-34c was
observed in the agomir group, in addition to an increased deficit in learning and
memory function in the Morris water maze test. Glutamate receptor ionotropic N
methyl-D-aspartate (NMDA) 2B (NR2B), phosphorylated (p)-reduced nicotinamide
adenine dinucleotide phosphate-dependent diflavin oxidoreductase 1 (NR1) and p
glutamate receptor 1 (GluR1) protein expression was detected in the hippocampus
using western blotting. Additionally, the downregulation of NR2B, p-NR1 and p
GluR1 in the miR-34c agomir group demonstrated that miR-34c may serve a negative
role in cognitive function in epileptic seizures, by dysregulating NMDA and alpha
amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, which are
associated with long-term potentiation.
PMID- 29344672
TI - Histone deacetylase inhibitor trichostatin A and autophagy inhibitor chloroquine
synergistically exert anti-tumor activity in H-ras transformed breast epithelial
cells.
AB - Histone deacetylase inhibitors (HDACIs) cause oncogene-transformed mammalian cell
death. Our previous study indicated that HDACIs activate forkhead box O1 (FOXO1)
and induce autophagy in liver and colon cancer cells. However, whether FOXO1 is
involved in HDACI-mediated oncogene-transformed mammalian cell death remains
unclear. In the present study, H-ras transformed MCF10A cells were used to
investigate the role of FOXO1 in this pathway. Results showed that trichostatin A
(TSA), a HDACI, activated apoptosis in MCF10A-ras cells, but not in MCF10A cells.
Furthermore, TSA activated FOXO1 via P21 upregulation, whereas the knockdown of
FOXO1 reduced TSA-induced cell death. In addition, TSA induced autophagy in
MCF10A and MCF10A-ras cells by blocking the mammailian target of rapamycin
signaling pathway. Furthermore, autophagy inhibition lead to higher MCF10A-ras
cell death by TSA, thus indicating that autophagy is essential in cell survival.
Taken together, the present study demonstrated that TSA causes oncogene
transformed cell apoptosis via activation of FOXO1 and HDACI-mediated autophagy
induction, which served as important cell survival mechanisms. Notably, the
present findings imply that a combination of HDACIs and autophagy inhibitors
produce a synergistic anticancer effect.
PMID- 29344673
TI - GOLPH2, a gene downstream of ras signaling, promotes the progression of
pancreatic ductal adenocarcinoma.
AB - Various studies have previously demonstrated that Golgi protein-73 (GOLPH2) is
overexpressed in tumorigenesis, which has been observed in hepatocellular
carcinoma and prostate cancer. However, the expression levels and specific
functions of GOLPH2 in the progression of pancreatic cancer remain to be
elucidated. The present study aimed to investigate the expression of GOLPH2 in
pancreatic ductal adenocarcinoma (PDAC) tissues and examined the effects of
GOLPH2 on the growth and migration of pancreatic cancer cells. In the present
study, the mRNA levels of GOLPH2 in PDAC cancer tissues were examined using RT
qPCR. The effects of GOLPH2 on the growth and migration of cancer cells were
examined using crystal violet and Boyden chamber assays. The study demonstrated
that the expression of GOLPH2 mRNA and protein was elevated in PDAC clinical
tissues. The growth and motility of the PDAC cells was enhanced following
overexpression of GOLPH2, whereas downregulating the expression of GOLPH2
impaired the growth, motility and tumorigenesis. Furthermore, GOLPH2 was observed
to interact with protein kinase B (Akt), which subsequently increased the
activity of Akt. In addition, GOLPH2 was revealed as a downstream gene of Ras
signaling and promoted the transformation of normal pancreatic cells. The results
of the present study revealed the important functions of GOLPH2 in PDAC, and
suggest that GOLPH2 may act as a promising therapeutic target for the treatment
of PDAC in the future.
PMID- 29344674
TI - Long non-coding RNA H1 promotes cell proliferation and invasion by acting as a
ceRNA of miR-138 and releasing EZH2 in oral squamous cell carcinoma.
AB - Long non-coding RNAs (lncRNAs) have been shown to play pivotal roles in various
types of human cancer, including oral squamous cell carcinoma (OSCC). However,
the potential mechanisms of action of lncRNAs in OSCC remain to be fully
elucidated. The aim of the present study was to further explore the potential
mechanisms of action of lncRNAs in OSCC. We first analyzed Gene Expression
Omnibus (GEO) datasets to investigate aberrantly expressed lncRNAs which may be
involved in the development of OSCC. Reverse transcription-quantitative PCR (RT
qPCR) was performed to analyze the expression levels of lncRNA H19. In addition,
the correlation between H19 expression and the clinical characteristics and
prognosis of patients with OSCC was statistically analyzed. The effects of H19
expression on OSCC cells were examined by using overexpression and RNA
interference approaches in vitro and in vivo. To examine the competitive
endogenous RNA (ceRNA) mechanisms, bioinformatics analysis and luciferase
reporter assay were performed. In addition, the correlation between H19 and
microRNA (miR)-138 was detected. H19 was found to be upregulated in OSCC tissues
and its high expression level was associated with the TNM stage and nodal
invasion, and also correlated with a shorter overall survival of patients with
OSCC. The knockdown of H19 significantly inhibited OSCC cell proliferation,
migration, invasion and epithelial-mesenchymal transition (EMT), and induced
apoptosis in vitro; it also suppressed subcutaneous tumor growth in vivo. In
addition, H19 was found to regulate the expression of oncogene enhancer of zeste
homolog 2 (EZH2) by competing with miR-138; the inhibition of miR-138 attenuated
the inhibitory effects of H19 knockdown on OSCC cells. On the whole, our findings
suggest that H19 functions as an oncogene by inhibiting miR-138 and facilitating
EZH2 expression in OSCC. Thus, lncRNA H1 may represent a potential therapeutic
target for OSCC.
PMID- 29344675
TI - Expression and prognostic significance of TRPV6 in the development and
progression of pancreatic cancer.
AB - In this study, we aimed to clarify the expression and biological functions of
TRPV6 in human pancreatic cancer (PC) tissue and pancreatic cancer (PC) cell
lines. TRPV6 was up-regulated in the primary cancer tissues from pancreatic
cancer (PC) patients. TRPV6 may regulate multiple proteins related to apoptosis,
cell cycle and metastasis pathways. Silencing TRPV6 significantly inhibited
invasion, proliferation and migration and induced apoptosis and cell cycle
arrest. TRPV6 plays a promising role of an oncogene in pancreatic carcinogenesis
and represents the new potential biomarker for PC.
PMID- 29344677
TI - Is vitamin D deficiency a public health concern for low middle income countries?
A systematic literature review.
AB - PURPOSE: Vitamin D deficiency has been receiving increasing attention as a
potential public health concern in low and lower-middle income countries (LMICs),
of which there are currently 83. We aimed to conduct a comprehensive systematic
literature review (SLR) of available data on vitamin D status and prevalence of
vitamin D deficiency in all 83 LMICs. METHODS: We followed the general
methodology for SLRs in the area of serum 25-hydroxyvitamin D. Highest priority
was placed on identifying relevant population-based studies, followed by cross
sectional studies, and to a lesser extent case-control studies. We adopted the
public health convention that a prevalence of vitamin D deficiency (serum 25
hydroxyvitamin D < 25/30 nmol/L) at > 20% in the entire population and/or at-risk
population subgroups (infants, children, women of child-bearing age, pregnancy)
constitutes a public health issue that may warrant intervention. RESULTS: Our SLR
revealed that of the 83 LMICs, 65% (n = 54 countries) had no published studies
with vitamin D data suitable for inclusion. Using data from the remaining third,
a number of LMICs had evidence of excess burden of vitamin D deficiency in one or
more population subgroup(s) using the above convention (Afghanistan, Pakistan,
India, Tunisia and Mongolia) as well as possibly other LMICs, albeit with much
more limited data. Several LMICs had no evidence of excess burden. CONCLUSION:
Vitamin D deficiency is a public health issue in some, but certainly not all,
LMICs. There is a clear need for targeting public health strategies for
prevention of vitamin D deficiency in those LMICs with excess burden.
PMID- 29344676
TI - Application of Genome Editing Techniques in Immunology.
AB - The idea of using the effector immune cells to specifically fight cancer has
recently evolved into an exciting concept of adoptive cell therapies. Indeed,
genetically engineered T cells expressing on their surface recombinant, cancer
targeted receptors have been shown to induce promising response in oncological
patients. However, in addition to exogenous expression of such receptors, there
is also a need for disruption of certain genes in the immune cells to achieve
more potent disease-targeted actions, to produce universal chimeric antigen
receptor-based therapies or to study the signaling pathways in detail. In this
review, we present novel genetic engineering methods, mainly TALEN and
CRISPR/Cas9 systems, that can be used for such purposes. These unique techniques
may contribute to creating more successful immune therapies against cancer or
prospectively other diseases as well.
PMID- 29344678
TI - Conservative antibiotic treatment for acute uncomplicated appendicitis is
feasible.
AB - PURPOSE: Appendectomy versus conservative antibiotic treatment (CAT) for children
with acute uncomplicated appendicitis (AUA) remains unresolved, with concerns
regarding the practicality of CAT. We analyzed our center's experience with CAT
for AUA, using a protocol with strict inclusion, exclusion and treatment
criteria. METHODS: Non-randomized, prospective cohort study included all children
admitted betwee 2014 and 2016, with clinical and laboratory tests suspicious for
AUA. Data collected included clinical signs and symptoms; laboratory, ultrasound
and pathology results. Follow-up was conducted through clinic visits, telephone
conversations and national registry analysis. RESULTS: Included in CAT: 362
children, 19 underwent appendectomy within 1-2 days. Overall, 75 were readmitted
for recurrent acute appendicitis during 22 months (6-43) follow-up. Thirty were
treated successfully with antibiotics a second time. The remaining 45 had
appendectomy. Overall, 86.8% underwent CAT with no surgery. Histology of all
recurrent AUA revealed no perforations. CONCLUSION: We confirm the feasibility of
conservative management of AUA in children. A rigorous diagnostic plan with
strict inclusion and exclusion criteria will lead to high success rate of CAT
with a strong safety profile. CAT does not compete with surgery or render
appendectomy unnecessary. It is a safe alternative to surgery in selected cases.
PMID- 29344679
TI - Distribution and dynamic expression of serotonin and dopamine in the nervous
system and ovary of Holothuria scabra during ovarian maturation.
AB - In the present study, the distribution and dynamic expression of serotonin and
dopamine in the nervous system and ovary of the sea cucumber, Holothuria scabra,
during different ovarian stages were investigated. We found that serotonin
immunoreactivity was more intense in the neurons and neuropils of the outer
ectoneural part, the inner hyponeural part, and the wall of hyponeural canal of
radial nerve cord during the mature stages of ovarian cycle, whereas dopamine
immunoreactivity was detected at a higher intensity in these tissues during the
early stages. Both neurotransmitters were detected in the ectoneural part of the
nerve ring. In the ovary, serotonin intensity was more intense in the cytoplasm
of late oocytes, while dopamine-immunoreactivity was more intense in the early
stages. The changes in the levels serotonin in the radial nerve cord and oocytes
are incremental towards the late stages of ovarian maturation. In contrast,
dopamine levels in the nervous tissues and oocytes were more intense in early
stages and became decremental towards the late stages. These findings suggest
that serotonin and dopamine may have opposing effects on ovarian development in
this sea cucumber species.
PMID- 29344680
TI - Acute and long-term outcome of focal atrial tachycardia ablation in the real
world: results of the german ablation registry.
AB - INTRODUCTION: Catheter ablation of focal atrial tachycardia (FAT) can be a
challenging procedure and results have been rarely described. The purpose of this
study was to determine the characteristics and results of FAT ablation in the
large cohort of the German Ablation Registry. METHODS: The German Ablation
Registry is a nationwide prospective multicenter database including 12566
patients who underwent an ablation procedure between 2007 and 2010. Among them
431 (3.4%) underwent an FAT ablation and 413 patients with documented locations
were analyzed. Patients were divided into three groups according to the FAT
location: biatrial (BiA, n = 31, 7.5%), left atrial (LA, n = 110, 26.5%), and
right atrial (RA, n = 272, 66%). RESULTS: Acute success rate was 84% (68 vs. 85
vs. 85% in biA, LA, and RA, respectively, p = 0.038). 4.8% of patients had an
early recurrence during hospitalization, most in biatrial location (p < 0.001).
No major acute complication occurred. At 12 months, 81% were asymptomatic or
improved. The incidence of major adverse cardiovascular and cerebrovascular
events (MACCE) was 3.7%. Arrhythmia freedom without antiarrhythmic drugs was 58%
and was lower in biA (34 vs. 56% in LA vs. 62% in RA, p = 0.019). Early
recurrence during hospitalization was an outstanding predictive factor for
recurrence during follow-up. CONCLUSION: In this large patient population, FAT
ablation had a relatively high acute success rate with a low complication rate.
During follow-up, the recurrence rate was high, particularly in biatrial
location. This was frequently predicted by an early recurrence during
hospitalization.
PMID- 29344681
TI - Timing of blood transfusion and oncologic outcomes in patients treated with
radical nephroureterectomy for upper tract urothelial carcinoma.
AB - PURPOSE: To evaluate the impact of timing of blood transfusion in patients with
upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy
(RNU). METHODS: Outcomes of consecutive patients with UTUC treated with RNU were
analyzed. Clinicopathologic factors were compared using Fisher's exact test or
the Wilcoxon rank-sum test between patients who received any transfusion and no
transfusion, and between patients receiving intraoperative transfusion only and
patients receiving no transfusion. Cancer-specific and overall survival were
estimated and multivariable analyses were performed to assess the impact of
timing of transfusion on clinical outcomes. RESULTS: Among 402 patients included
in this study, 71 (17.6%) patients received a transfusion at any point and 27
(6.7%) patients received an intraoperative blood transfusion. Transfusion at any
time, patient comorbidity, high grade, advanced stage, positive surgical margins,
low preoperative hemoglobin, longer operative duration, and increased blood loss
were significantly associated with cancer-specific survival (DSS) on univariable
analysis (HR 1.85, 95% CI 1.20-2.85, p < 0.005). In the multivariable analysis,
transfusion at any point was not a prognostic factor (HR 1.00, 95% CI 0.60-1.68,
p = 0.99). When examining intraoperatively transfusion only, transfusion was
significantly associated with DSS (HR 1.91, 95% CI 1.01-3.59, p = 0.045) but no
longer significant in multivariable analysis (HR 0.72, 95% CI 0.32-1.65, p =
0.440). CONCLUSIONS: Our study indicates that the administration of blood
transfusion either intraoperatively or postoperatively is not associated with
clinical or oncological outcomes in patients with upper tract urothelial
carcinoma when adjusted for other factors in multivariable analysis. Further
study is required.
PMID- 29344682
TI - 68Ga-prostate specific membrane antigen (PSMA) positron emission tomography (PET)
for primary staging of high-risk prostate cancer: a systematic review.
AB - PURPOSE: To systematically review currently available data on 68Ga-prostate
specific membrane antigen (PSMA) positron emission tomography (PET) used for the
primary staging of high-risk prostate cancer. METHODS: We performed critical
reviews of EMBASE, Web of Science (including MEDLINE) and Cochrane databases in
October 2016 according to the Preferred Reporting Items for Systematic Review and
Meta-analysis statement. We included studies that utilized 68Ga-PSMA PET for
primary staging of prostate cancer. Quality was assessed using the Critical
Appraisal Skills Programme checklist for diagnostic test studies. RESULTS:
Following our systematic search strategy, 12 studies were included for
assessment. These studies comprised a total of 322 patients who underwent 68Ga
PSMA PET scanning for the purpose of primary staging. Only 5 of these studies
included histopathologic correlation data. High variation in methodology and
outcomes such as sensitivity (range 33-99%) and specificity (> 90%) was seen
across all studies. The ability of 68Ga-PSMA PET to detect malignant lesions was
evident across studies, with most studies demonstrating increased detection rates
with respect to conventional imaging modalities. CONCLUSIONS: In the primary
staging of prostate cancer 68Ga-PSMA PET appears to outperform traditional
imaging modalities. Overall, there are few high-quality studies investigating
68Ga-PSMA PET in this sub-group highlighting the need for formal assessment of
PSMA PET in the form of large-volume, prospective studies.
PMID- 29344684
TI - Novel Injection Technique for Malar Cheek Volume Restoration.
PMID- 29344683
TI - The root transcriptome of Achyranthes bidentata and the identification of the
genes involved in the replanting benefit.
AB - KEY MESSAGE: The transcriptome profiling in replanting roots revealed that
expression pattern changes of key genes promoted important metabolism pathways,
antioxidant and pathogen defense systems, adjusted phytohormone signaling and
inhibited lignin biosynthesis. The yield of the medicinal plant Achyranthes
bidentata could be significantly increased when replanted into a field cultivated
previously for the same crop, but the biological basis of this so-called
"replanting benefit" is unknown. Here, the RNA-seq technique was used to identify
candidate genes responsible for the benefit. The analysis of RNA-seq libraries
prepared from mRNA extracted from the roots of first year planting (normal
growth, NG) and second year replanting (consecutive monoculture, CM) yielded
about 40.22 GB sequencing data. After de novo assembly, 87,256 unigenes were
generated with an average length of 1060 bp. Among these unigenes, 55,604 were
annotated with public databases, and 52,346 encoding sequences and 2881
transcription factors were identified. A contrast between the NG and CM libraries
resulted in a set of 3899 differentially transcribed genes (DTGs). The DTGs
related to the replanting benefit and their expression profiles were further
analyzed by bioinformatics and qRT-PCR approaches. The major differences between
the NG and CM transcriptomes included genes encoding products involved in
glycolysis/gluconeogenesis, glutathione metabolism and antioxidant defense, in
aspects of the plant/pathogen interaction, phytohormone signaling and
phenylpropanoid biosynthesis. The indication was that replanting material enjoyed
a stronger level of defense systems, a balance regulation of hormone signals and
a suppression of lignin formation, thereby promoting root growth and development.
The study provides considerable significant insights for a better understanding
of the molecular mechanism of the replanting benefit and suggests their possible
application in developing methods to reinforce the effects in medicinal plants.
PMID- 29344685
TI - Long-Term Safety and Efficacy of Botulinum Toxin A Treatment in Adolescent
Patients with Axillary Bromhidrosis.
AB - BACKGROUND: For adolescent bromhidrosis, the long-term safety and efficacy of
botulinum toxin type A (BTX-A) treatment are not clear to date. PATIENTS AND
METHODS: From June 2011 to July 2016, 62 adolescent patients with primary
axillary bromhidrosis were recruited and 50 U of BTX-A was administered in each
axilla. Repetitive injections were performed when the malodor returned. RESULTS:
The average follow-up was 2.64 years. There were no reported local or systemic
adverse effects. After the first BTX-A injection, 61.3% of patients (38/62)
maintained the duration of more than 4 weeks. Of these patients, 21 patients
underwent two sessions, 8 patients underwent three sessions, and 4 patients
underwent four sessions. Twenty-four of sixty-two (38.7%) of patients had the
duration of < 4 weeks. The second injection with the same dose was immediately
administered, and the resulting duration increased to 9 weeks. Nineteen patients
received the third injection with 100 U per underarm, and the resulting duration
was extended up to 16 weeks. Overall, 82% of patients (51/62) ranked the BTX-A
treatment to be very good or good. CONCLUSION: For adolescent axillary
bromhidrosis, BTX-A injection is safe and effective over a long-term follow-up.
The duration of efficacy is variable, and the dosage should be fine-tuned based
on the individual response. LEVEL OF EVIDENCE IV: This journal requires that
authors assign a level of evidence to each article. For a full description of
these Evidence-Based Medicine ratings, please refer to the Table of Contents or
the online Instructions to Authors www.springer.com/00266 .
PMID- 29344686
TI - Executive control and faithfulness: only long-term romantic relationships require
prefrontal control.
AB - Individuals in the early stages of a romantic relationship generally express
intense passionate love toward their partners. This observation allows us to
hypothesize that the regulation of interest in extra-pair relationships by
executive control, which is supported by the function of the prefrontal cortex,
is less required in individuals in the early stages of a relationship than it is
in those who are in a long-term relationship. To test this hypothesis, we asked
male participants in romantic relationships to perform a go/no-go task during
functional magnetic resonance imaging (fMRI), which is a well-validated task that
can measure right ventrolateral prefrontal cortex (VLPFC) activity implicated in
executive control. Subsequently, the participants engaged in a date-rating task
in which they rated how much they wanted to date unfamiliar females. We found
that individuals with higher right VLPFC activity better regulated their interest
in dates with unfamiliar females. Importantly, this relationship was found only
in individuals with long-term partners, but not in those with short-term
partners, indicating that the active regulation of interest in extra-pair
relationships is required only in individuals in a long-term relationship. Our
findings extend previous findings on executive control in the maintenance of
monogamous relationships by highlighting the role of the VLPFC, which varies
according to the stage of the romantic relationship.
PMID- 29344687
TI - Risk Factors for Early Postoperative Small Bowel Obstruction After Anterior
Resection for Rectal Cancer: Methodological Issues: Reply.
PMID- 29344688
TI - Inflammation-Based Prognostic Score Predicts Postoperative Survival of Patients
with Interstitial Pneumonia After Undergoing Lung Cancer Resection.
AB - OBJECTIVES: Idiopathic interstitial pneumonias (IIPs) are associated with an
increased risk of lung cancer. Glasgow prognostic score (GPS), which uses serum C
reactive protein (CRP) and albumin levels to indicate systemic inflammatory
response and nutrition level, has been reported to be a predictor of overall
survival in patients with various types of cancer. We evaluated the usefulness of
GPS for prediction of survival of patients with both lung cancer and IIPs
following a lung resection procedure. METHODS: Patients with IIPs who underwent
lung cancer resection from January 2006 through December 2015 were investigated.
Routine laboratory measurements, including serum CRP and albumin for determining
GPS, were performed before the operation. Univariate and multivariate analyses
with a COX proportional hazards regression model were used to identify
independent risk factors for overall survival (OS), relapse-free survival (RFS),
cancer-specific survival (CSS), and other disease-specific survival (ODSS).
RESULTS: A total of 135 patients underwent lung resection during the study
period. Multivariate analysis selected sublobar resection (p = 0.035), UIP
pattern (p = 0.025), and GPS of 1-2 (p = 0.042) as predictive factors associated
with OS, while GPS of 1-2 (p = 0.039) was shown to be a predictive factor
associated with RFS. Multivariate analysis also revealed pTNM (p < 0.001), usual
interstitial pneumonia pattern (p = 0.006), and GPS of 2 (p = 0.003) as
predictive factors associated with CSS, while univariate analysis indicated pTNM
(p = 0.042), GPS of 1 (p = 0.044), and %DLCO (p = 0.038) as predictive factors
associated with ODSS. CONCLUSION: GPS is an independent prognostic factor of OS
and RFS in lung cancer patients with IIPs undergoing a lung resection procedure.
Furthermore, a GPS of 2 was found to be associated with CSS following lung cancer
resection, while a score of 1 was associated with ODSS.
PMID- 29344689
TI - Early Versus Late Tracheostomy in Trauma Patients: A Propensity-Matched Cohort
Study of 5 Years' Data at a Single Institution in Korea.
AB - BACKGROUND: Although there have been many studies dealing with tracheostomy
timing in trauma patients, the optimal timing is still being debated. This study
aimed to compare outcomes between early tracheostomy (ET) and late tracheostomy
(LT) in trauma populations to estimate the optimal timing of tracheostomy after
intubation. METHODS: We retrospectively reviewed the 5 years' data of trauma
patients who underwent tracheostomy during their acute intensive care unit (ICU)
stay. The cases were divided into two groups: ET was defined as tracheostomy
performed within 7 days after intubation, and LT, after the seventh day.
Propensity score matching was utilized using a 1-to-1 matching technique, and
outcomes between two groups were compared. RESULTS: Among 236 enrolled patients,
76 met the criteria for ET and 160 were included for LT. Using propensity
matching, 70 patients who met the criteria for ET were matched to 70 patients in
the LT. Based on the comparison of outcomes after matching, ET showed
significantly shorter values than LT in overall ventilator duration, length of
stay at the ICU, and post-tracheostomy ventilation duration. Furthermore, the
incidence of pneumonia was significantly lower with ET than with LT, although the
rate of postoperative complications showed no significant differences.
CONCLUSIONS: We suggest that ET should be considered in trauma patients needing
prolonged mechanical ventilation. Also, we recommend that surgeons perform
tracheostomy as early as within 7 days after intubation to not only reduce the
ventilation and ICU days but also prevent pneumonia without worrying about an
increase in postoperative complications.
PMID- 29344690
TI - [Globalization: challenges in abdominal surgery for migrants and refugees].
AB - The increasing number of refugees, migrants and international travelers
influences the surgical spectrum of abdominal diseases. The aim of this review is
to familiarize surgeons with specific diseases which are endemic in the patients'
countries of origin and are likely to be diagnosed with increasing incidence in
Germany. Low levels of hygiene in the countries of origin or refugee camps is
associated with a high incidence of numerous infections, such as helminth
infections, typhoid fever or amoebiasis, which if untreated can cause surgical
emergencies. Historically, some of them were common in Germany but have been more
or less eradicated because of the high socioeconomic standard. Echinococcosis and
Chagas disease are frequently treated surgically while schistosomiasis can mimic
intestinal cancer. Abdominal tuberculosis presents in a variety of abdominal
pathologies and frequently causes diagnostic uncertainty. Sigmoid volvulus has a
very low incidence among Europeans, but is one of the most common abdominal
surgical conditions of adults in endemic countries. The number of patients who
eventually undergo surgery for these conditions might be relatively low; however,
surgeons must be aware of them and consider them as differential diagnoses in
refugees and migrants with acute or chronic abdominal symptoms.
PMID- 29344691
TI - [A rare cause of acute pneumoperitoneum].
PMID- 29344692
TI - The epidemiology of wrist fractures in older men: the Osteoporotic Fractures in
Men (MrOS) study.
AB - : There is limited wrist fracture information on men. Our goal was to calculate
frequency and identify risk factors for wrist fracture in the Osteoporotic
Fractures in Men (MrOS) study. We confirmed that fracture history and certain
medications are predictors, and identified novel predictors including markers of
kidney function and physical performance. INTRODUCTION: To calculate the
incidence of wrist fractures and their risk factors in older community-dwelling
men from the US Osteoporotic Fractures in Men (MrOS) study. METHODS: Using
triannual postcards, we identified incident wrist fractures (centrally confirmed
by radiology) in men aged >= 65. Potential risk factors included the following:
demographics, lifestyle, bone mineral density (BMD), selected medications,
biomarkers, and physical function and performance measures. Both baseline and
time-varying models were adjusted for age, race/ethnicity, MrOS geographic
location, and competing mortality risks. RESULTS: We observed 97 incident wrist
fractures among 5875 men followed for an average of 10.8 years. The incidence of
wrist fracture was 1.6 per 1000 person-years overall and ranged from 1.0 among
men aged 65-69 to 2.4 among men age >= 80. Significant predictors included the
following: fracture history after age 50 [hazard ratio (95% CI): 2.48 (1.65,
3.73)], high serum phosphate [1.25 (1.02, 1.53)], use of selective serotonin
receptor inhibitor (SSRI) [3.60 (1.96, 6.63), decreased right arm BMD [0.49
(0.37, 0.65) per SD increase], and inability to perform the grip strength test
[3.38 (1.24, 9.25)]. We did not find associations with factors commonly
associated with wrist and other osteoporosis fractures like falls, diabetes,
calcium and vitamin D intake, and alcohol intake. CONCLUSIONS: Among these older,
community-dwelling men, we confirmed that fracture history is a strong predictor
of wrist fractures in men. Medications such as SSRIs and corticosteroids also
play a role in wrist fracture risk. We identified novel risk factors including
kidney function and the inability to perform the grip strength test.
PMID- 29344694
TI - Towards a better production of bacterial exopolysaccharides by controlling
genetic as well as physico-chemical parameters.
AB - Bacterial extracellular polymeric substances, which are basically bacterial
metabolites, have currently become a subject of great concern of modern day
microbiologists and biotechnologists. Among these metabolites, bacterial
exopolysaccharides or EPS, in particular, have gained a significant importance.
EPS are formed by the bacteria in their late exponential or stationary phase of
growth under special situations for specific purposes. They take part in the
formation of bacterial biofilms. There is a great diversity in the types of EPS.
Strikingly enough, a same species of bacterium can produce different types of EPS
under different situations. The importance of EPS is largely because of their
different applications in various industries. Now that the bacterial EPS has got
the potentiality to become an upcoming tool in various futuristic applications of
human benefit, the focus currently develops towards how better they can be
produced in the laboratory by promoting the favorable factors for their
production. While studying with different EPS forming bacteria, both the
intrinsic factors like genetic configuration of the bacteria and the extrinsic
factors like culture conditions under the influence of different physico-chemical
parameters in order to maximize the EPS production have been taken into
consideration. Both the factors have proved their worth. Hence, towards a better
outcome for EPS production, it is indicated that a genetic manipulation of the
bacteria should be synchronized with a proper selection of its culture condition
by controlling different physico-chemical parameters.
PMID- 29344693
TI - Triplet-Based Codon Organization Optimizes the Impact of Synonymous Mutation on
Nucleic Acid Molecular Dynamics.
AB - Since the elucidation of the genetic code almost 50 years ago, many nonrandom
aspects of its codon organization remain only partly resolved. Here, we
investigate the recent hypothesis of 'dual-use' codons which proposes that in
addition to allowing adjustment of codon optimization to tRNA abundance, the
degeneracy in the triplet-based genetic code also multiplexes information
regarding DNA's helical shape and protein-binding dynamics while avoiding
interference with other protein-level characteristics determined by amino acid
properties. How such structural optimization of the code within eukaryotic
chromatin could have arisen from an RNA world is a mystery, but would imply some
preadaptation in an RNA context. We analyzed synonymous (protein-silent) and
nonsynonymous (protein-altering) mutational impacts on molecular dynamics in
13823 identically degenerate alternative codon reorganizations, defined by codon
transitions in 7680 GPU-accelerated molecular dynamic simulations of implicitly
and explicitly solvated double-stranded aRNA and bDNA structures. When compared
to all possible alternative codon assignments, the standard genetic code
minimized the impact of synonymous mutations on the random atomic fluctuations
and correlations of carbon backbone vector trajectories while facilitating the
specific movements that contribute to DNA polymer flexibility. This trend was
notably stronger in the context of RNA supporting the idea that dual-use codon
optimization and informational multiplexing in DNA resulted from the
preadaptation of the RNA duplex to resist changes to thermostability. The
nonrandom and divergent molecular dynamics of synonymous mutations also imply
that the triplet-based code may have resulted from adaptive functional expansion
enabling a primordial doublet code to multiplex gene regulatory information via
the shape and charge of the minor groove.
PMID- 29344695
TI - Succession of microbial communities and changes of incremental oil in a post
polymer flooded reservoir with nutrient stimulation.
AB - Further exploitation of the residual oil underground in post-polymer flooded
reservoirs is attractive and challengeable. In this study, indigenous microbial
enhanced oil recovery (IMEOR) in a post-polymer flooded reservoir was performed.
The succession of microbial communities was revealed by high-throughput
sequencing of 16S rRNA genes and changes of incremental oil were analyzed. The
results indicated that the abundances of reservoir microorganisms significantly
increased, with alpha diversities decreased in the IMEOR process. With the
intermittent nutrient injection, microbial communities showed a regular change
and were alternately dominated by minority populations: Pseudomonas and
Acinetobacter significantly increased when nutrients were injected; Thauera,
Azovibrio, Arcobacter, Helicobacter, Desulfitobacterium, and Clostridium
increased in the following water-flooding process. Accompanied by the stimulated
populations, higher oil production was obtained. However, these populations did
not contribute a persistent level of incremental oil in the reservoir. In
summary, this study revealed the alternative succession of microbial communities
and the changes of incremental oil in a post-polymer flooded reservoir with
intermittent nutrient stimulation process.
PMID- 29344696
TI - Reconstruction of the medial patellotibial ligament results in favorable clinical
outcomes: a systematic review.
AB - PURPOSE: The medial patellotibial ligament (MPTL), the medial patellofemoral
ligament (MPFL), and the medial patellomeniscal ligament (MPML) support the
stability of the patellofemoral joint. The purpose of this systematic review was
to report the surgical techniques and clinical outcomes of the repair or
reconstruction of the MPTL in isolation or concomitant with the MPFL and/or other
procedures. METHODS: A systematic review of the literature was conducted.
Inclusion criteria were articles in the English language that reported clinical
outcomes of the reconstruction of the MPTL in isolation or in combination with
the MPFL and/or other procedures. Included articles were then cross-referenced to
find additional journal articles not found in the initial search. The
methodological quality of the articles was determined using the Coleman
Methodology Score. RESULTS: Nineteen articles were included detailing the
clinical outcomes of 403 knees. The surgical procedures described included
hamstrings tenodesis with or without other major procedures, medial transfer of
the medial patellar tendon with or without other major procedures and the
reconstruction of the MPTL in association with the MPFL. Overall, good and
excellent outcomes were achieved in > 75% of cohorts in most studies and
redislocations were < 10%, with or without the association of the MPFL. An
exception was one study that reported a high failure rate of 82%. Results were
consistent across different techniques. The median CMS for the articles was 66
out of 100 (range 30-85). CONCLUSION: Across different techniques, the outcomes
are good with low rates of recurrence, with one article reporting a high rate of
recurrence. Quality of the articles is variable, from low to high. Randomized
control trials are needed for a better understanding of the indications, surgical
techniques, and clinical outcomes. This systematic review suggests that the
reconstruction of the MPTL leads to favorable clinical outcomes and supports the
role of the procedure as a valid surgical patellar stabilization procedure. LEVEL
OF EVIDENCE: IV: systematic review of level I-IV studies.
PMID- 29344697
TI - Could spouses of colorectal cancer patients possess higher risk of developing
colorectal cancer?
PMID- 29344698
TI - Concentrations of Cadmium, Copper, and Zinc in Macrobrachium rosenbergii (Giant
Freshwater Prawn) from Natural Environment.
AB - This study analyzed the levels of cadmium (Cd), copper (Cu), and zinc (Zn) by the
flame atomic absorption spectrophotometer (FAAS), in the muscle tissues,
exoskeletons, and gills from freshwater prawn (Macrobrachium rosenbergii) (n =
20) harvested from natural habitat in Kerang River, Malaysia on 25th November
2015. Significant increase of the metals level in muscle tissue and gill (r >
0.70, p < 0.05) were observed with increase in length except for Cu in gills. No
relationship was found between metals level in exoskeleton and length. The
concentrations of Cd, Cu and Zn were significantly higher (p < 0.05) in males
(muscle tissues and exoskeleton) except for Cd in exoskeleton. In gills, only Cu
was significantly higher (p < 0.05) in female than male. All samples contained
metals below the permissible limit for human consumption (i.e., Cd < 2.00 mg/kg;
Cu < 30.00 mg/kg; Zn < 150 mg/kg). Annual metals monitoring in prawn and
environmental samples is recommended to evaluate changes of metals
bioaccumulation and cycling in the system, which is useful for resources
management.
PMID- 29344699
TI - Feasibility study of MR-guided transgluteal targeted in-bore biopsy for
suspicious lesions of the prostate at 3 Tesla using a freehand approach.
AB - OBJECTIVE: The aim of our study was (1) to establish an in-bore targeted biopsy
of suspicious prostate lesions, avoiding bowel penetration using a transgluteal
approach and (2) to assess operator setup, patient comfort and safety aspects in
the clinical setting for freehand real-time MR-guidance established for
percutaneous procedures in an open MR-scanner. MATERIAL AND METHODS: 30 patients
with suspect prostate lesions were biopsied in a cylindrical 3T-MRI system using
a transgluteal approach in freehand technique. One to three biopsies were sampled
using continuous dynamic imaging. Size, location and visibility of the lesion,
intervention time, needle artefact size, interventional complications and
histopathological diagnosis were recorded. RESULTS: All biopsies were technically
successful. Nineteen patients showed evidence of prostate carcinoma. Cancer
detection rate was 50 % in patients with previously negative TRUS-biopsy. The
average intervention time was 26 min including a learning curve as the time was
13 min by the end of the study. No antibiotic prophylaxis was performed as none
of the patients showed signs of infection. CONCLUSIONS: MR-guided targeted
freehand biopsies of prostate lesions using a transgluteal approach are both
technically feasible and time efficient in a standard closed-bore 3T-MR scanner
as well as safe for the individual patient. KEY POINTS: * Open-bore freehand
interventional principles were adapted to closed-bore systems. * Prostate MR
guided freehand biopsies were feasible in a clinical setting. * A transgluteal
approach provides a short and simplified work flow. * An inoculation of the
prostate with bowel flora is avoided. * The intervention time is comparable to
the stereotactic approach.
PMID- 29344700
TI - Dual mobility hip arthroplasty provides better outcomes compared to
hemiarthroplasty for displaced femoral neck fractures: a retrospective
comparative clinical study.
AB - PURPOSE: Total hip arthroplasty with a dual mobility cup (DMC) is a proposed
alternative to the widely performed bipolar hemiarthroplasty (BHA) for treating
displaced intracapsular femoral neck fractures (DFNF) in the elderly. However,
the comparison between the two modalities has not been extensively conducted thus
far. METHODS: A retrospective cohort study was conducted with DFNF patients aged
over 65 years who were treated either by BHA or DMC. After propensity matching
each group comprised 84 patients (168 patients in total) and was analyzed using
peri-operative and post-operative parameters. RESULTS: Mean follow-up durations
were 22.1 and 21.7 months in the BHA and DMC groups, respectively. The BHA group
demonstrated significantly less intra-operative blood loss (p = 0.001) and a
shorter length of operation (p < 0.001). However, there was no difference in one
year mortality (p = 0.773). The Harris hip score (HHS) was significantly higher
(p = 0.018) in the DMC group. The dislocation rate was not different between the
two groups (p = 1.000). CONCLUSION: In DFNF patients aged over 65 years, short
term observation showed DMC to be the preferred treatment over BHA with better
clinical outcome, without disadvantages in mortality or dislocation rate. Further
long-term investigations are recommended to strengthen these results.
PMID- 29344701
TI - The fate of immunocompromised patients in the treatment of chronic periprosthetic
joint infection: a single-centre experience.
AB - PURPOSE: Immunocompromised patients with periprosthetic joint infection (PJI) are
rare and currently there are no reliable guidelines according to which these
infections can be successfully managed. The purpose of this study was to report
the clinical course of different strategies for treatment of PJI in frail
patients. METHODS: A retrospective analysis between 2004 and 2015 included 29
immunocompromised patients (13 hips and 16 knees) with chronic PJI who underwent
one-stage revision or debridement, antibiotics and implant retention (DAIR).
Patients were stratified according to the Musculoskeletal Infection Society
(MSIS) staging system and the clinical course included recurrence of infection
and functional outcomes which were extracted from patients' charts. The average
follow-up was 68 months (range, 26-149 months). RESULTS: Sixteen of the 29
patients had recurrent infections. At last follow-up, 13 patients were on chronic
suppressive antibiotic therapy, three patients died but not one death was
considered to be related to the infection. A recurrent infection was observed in
13 of the 24 medically compromised hosts (MSIS type B). Sixteen of the 24
patients underwent one-stage revision; another eight of them underwent DAIR. The
infection recurred in three of the five patients (60%) with the worst host grades
(MSIS type C). One-stage revision was performed in one of the five patients and
the remaining four patients received DAIR. CONCLUSION: Our results show that we
should compromise our expectation and intemperate treatment for such a
population. The goals of PJI treatment in these patients should take into account
their preferences and may pay more attention to the concept of disease control
rather than cure, especially for patients with severe comorbidities (MSIS C).
LEVEL OF EVIDENCE: Therapeutic Level IV.
PMID- 29344702
TI - [Mesenchymal abdominal tumors].
PMID- 29344704
TI - [The role of PSMA PET-CT in patients with metastatic prostate cancer].
AB - Prostate-specific membrane antigen (PSMA) positron emission tomography-computed
tomography (PET-CT) imaging for the localization of prostate cancer is
increasingly available in Germany. The advances and limitations in different
disease stages are reviewed. As the clinical relevance of oligometastatic disease
in primary cancer detected by PSMA PET-CT imaging is not yet completely
understood, it should only be used in clinical trials. In recurrent prostate
cancer after therapy with curative intent, PSMA PET-CT shows encouraging
potential for the planning of salvage therapy. In metastatic castration-resistant
prostate cancer evidence for its use is not available.
PMID- 29344705
TI - [Which foot deformities should be radiologist be familiar with?]
AB - Most deformities of the foot are visible at birth and can be diagnosed without
imaging. They can be divided into congenital flexible, congenital structural and
acquired foot deformities. The most common congenital flexible foot deformity in
children is the metatarsus adductus, which usually requires no long-term therapy.
Regarding congenital structural deformities, such as the clubfoot and talus
verticalis, plaster therapy should be started during the first week of life, so
that by the end of the first year of life and the beginning of the
verticalization, a pain-free resilient foot with normal function is present.
Imaging is usually only necessary if a relapse arises. Coalitio of the tarsal
bones is often visible only in the course of growth through the development of a
rigid flatfoot and always requires imaging to confirm the diagnosis. This article
is intended to give the radiologist an overview of the most important deformities
and to inform about their course and therapy.
PMID- 29344706
TI - Long-term follow-up of 1217 consecutive short-stem total hip arthroplasty (THA):
a retrospective single-center experience.
AB - BACKGROUND: An arthroplasty registry in Germany has been recently established but
long-term results for most short-stem innovations are missing. Short-stem hip
arthroplasty is usually indicated in young active patients. Our indication was
extended to older age groups, femoral neck fractures (FNF), and dysplasia. We
evaluated all total hip arthroplasties (THAs) in this population with a collum
femoris preserving stem (CFP) performed from 2003 to 2013. METHODS: A consecutive
cohort of 1217 CFP THAs with a mean age of 68.7 years was followed
retrospectively for a median of 4.8 years (patient follow-up interquartile range
from 3.0 to 6.9 years). A questionnaire, which we used in two previous studies,
was answered by 89.15% of patients and included information regarding complaints,
grade of satisfaction, re-operations, and dislocation. Of the 1217 patients, 77
had died. Survival of the stem and the cup was assessed using a competing risks
approach according to an Aalen-Johanson estimator with revision for septic or
aseptic loosening or death as a competing endpoint. RESULTS: Of the patients who
answered the questionnaire, 92.5% had no complaints related to the procedures. In
all 1217 patients, there were 43 revisions (4.2%) as follows: stem and cup
revisions due to aseptic loosening of the stem (n = 10), infections (n = 6), pain
(n = 4), or trauma (n = 3); cup revisions due to aseptic loosening (n = 3),
dislocation (n = 5), and offset revisions (n = 12). Survivorship was 96% for the
stem and 99% for the cup 9 years postoperatively. Statistical analysis confirmed
a higher risk for revision in patients with a younger age (p = 0.033), male sex
(p = 0.040), dysplasia (p = 0.032), and undersized or extra-large stems for stem
revisions (p = 0.001) and female sex (p = 0.036) for cup revisions. FNF (p >
0.20) and age >= 80 years (p = 0.114) had no higher risk for loosening of the
stem. Our data is also compared with the current literature, especially with the
available CFP studies. CONCLUSION: The survival rate of the CFP stem was as high
as 96% after 9 years of followup which compares well-to-previously published long
term survival rates. There is no higher risk for revision in patients 80 years
old or older and in cases with femoral neck fractures. The CFP preserves also
allowed using standard stems in the rare cases of revision.
PMID- 29344707
TI - Effects of the establishment of a trauma center and a new protocol on patients
with hemodynamically unstable pelvic fractures at a single institution in Korea.
AB - PURPOSE: The aim of this study was to determine whether the outcomes of patients
with hemodynamically unstable pelvic bone fractures changed after the
introduction of a protocol including extraperitoneal pelvic packing (EPP) and the
establishment of a trauma center. METHODS: We analyzed data of adult patients (>=
18 years old) with hemodynamically unstable pelvic bone fractures who visited a
single trauma center from February 2009 to October 2016. In July 2014, a new
protocol for pelvic fractures was implemented, and a trauma center was
established. Therefore, patient outcomes were compared by period (period I: pre
protocol vs. period II: post-protocol). RESULTS: Seventy-nine patients with
hemodynamically unstable pelvic bone fractures were recruited. The time to
angiographic embolization after arrival at the emergency room decreased
significantly in period II when compared to period I (182.9 vs. 268.9 min,
respectively, p < 0.001). The time required to intervention, including EPP, also
decreased, from 268.9 +/- 132.4 min in period I to 141.9 +/- 79.9 min in period
II (p < 0.001). The overall mortality rate decreased from 47.2% in period I to
23.3% in period II (p = 0.033), and mortality related to hemorrhagic shock in
particular, was significantly lowered, from 27.8% in period I to 4.7% in period
II (p = 0.009). CONCLUSIONS: The establishment of a trauma center and the
implementation of a new protocol that included EPP were effective in the
treatment of patients with hemodynamically unstable pelvic fractures.
PMID- 29344708
TI - Treatment of combined traumatic brain injury and hemorrhagic shock with
fractionated blood products versus fresh whole blood in a rat model.
AB - INTRODUCTION: Treatment of combined traumatic brain injury and hemorrhagic shock,
poses a particular challenge due to the possible conflicting consequences. While
restoring diminished volume is the treatment goal for hypovolemia, maintaining
adequate cerebral perfusion pressure and avoidance of secondary damage remains a
treatment goal for the injured brain. Various treatment modalities have been
proposed, but the optimal resuscitation fluid and goals have not yet been clearly
defined. A growing body of evidence suggests that in hypovolemic shock,
resuscitation with fresh whole blood (FWB) may be superior to component therapy
without platelets (which are likely to be unavailable in the pre-hospital
setting). Nevertheless, the effects of this approach have not been studied in the
combined injury. Previously, in a rat model of combined injury we have found that
mild resuscitation to MABP of 80 mmHg with FWB is superior to fluid resuscitation
or aggressive resuscitation with FWB. In this study, we investigate the
physiological and neurological outcomes in a rat model of combined traumatic
brain injury (TBI) and hypovolemic shock, submitted to treatment with varying
amounts of FWB, compared to similar resuscitation goals with fractionated blood
products-red blood cells (RBCs) and plasma in a 1:1 ratio regimen. MATERIALS AND
METHODS: 40 male Lewis rats were divided into control and treatment groups. TBI
was inflicted by a free-falling rod on the exposed cranium. Hypovolemia was
induced by controlled hemorrhage of 30% blood volume. Treatment groups were
treated either with fresh whole blood or with RBC + plasma in a 1:1 ratio,
achieving a resuscitation goal of a mean arterial blood pressure (MAP) of 80 mmHg
at 15 min. MAP was assessed at 60 min, and neurological outcomes and mortality in
the subsequent 24 h. RESULTS: At 60 min, hemodynamic parameters were improved
compared to controls, but not significantly different between treatment groups.
Survival rates at 48 h were 100% for both of the mildly resuscitated groups (MABP
80 mmHg) with FWB and RBC + plasma. The best neurological outcomes were found in
the group mildly resuscitated with FWB and were better when compared to
resuscitation with RBC + plasma to the same MABP goal (FWB: Neurological Severity
Score (NSS) 6 +/- 2, RBC + plasma: NSS 10 +/- 2, p = 0.02). CONCLUSIONS: In this
study, we find that mild resuscitation with goals of restoring MAP to 80 mmHg
(which is lower than baseline) with FWB, provided better hemodynamic stability
and survival. However, the best neurological outcomes were found in the group
resuscitated with FWB. Thus, we suggest that resuscitation with FWB is a feasible
modality in the combined TBI + hypovolemic shock scenario, and may result in
improved outcomes compared to platelet-free component blood products.
PMID- 29344709
TI - Microbial Characterization of Methanogenic and Iron-reducing Consortium in
Reactors with Polychlorinated Biphenyls.
AB - Recent papers have confirmed current environmental pollution and the continuous
release of polychlorinated biphenyls (PCBs) despite the prohibition of its
manufacture worldwide. As the dehalogenating microorganisms are able to remove
halogens from various analogous compounds, the characterization of PCB
metabolisms can improve the degradation of similar compounds. Thus, this study
extensively evaluated the microbial community developed in methanogenic and iron
reducing reactors. The horizontal-flow anaerobic reactor (HAIB) with real waste
of Aroclor (1 mL L-1) was fed with mineral medium, ethanol, and sodium formate.
Bacteria belonging to Thermotogaceae (Thermotogae), Geobacteraceae, Chloroflexi,
Proteobacteria, and Firmicutes (Clostridium) were identified in the HAIB reactor.
Bacteria belonging to the Chloroflexi, Firmicutes, and Geobacteraceae are
associated with the degradation of hydrocarbons and could be related to the
Aroclor waste in this paper. Furthermore, 5.26 * 1012 cells gTVS-1 of iron
reducing bacteria were quantified by the most probable number method in the HAIB
reactor, suggesting that this group has an important role in aromatic
degradation. Moreover, the evaluation of methanogenic and iron-reducing
microorganisms in batch reactors with Aroclor 1260 was performed and the biomass
growth was not affected by the addition of PCB. The methane production reached
0.38 umol CH4 gTVS-1 and the iron reduction attained 90% in batch reactors.
Through microbial analyses from HAIB and batch reactors, lower diversity was
evidenced in the presence of PCB. This paper indicates the relevant role of iron
reducing organisms and Chloroflexi, Geobacteraceae, and Firmicutes group in PCB
metabolism.
PMID- 29344710
TI - Radiation Doses to Operators in Hepatobiliary Interventional Procedures.
AB - PURPOSE: The primary aim of this study is to provide a summary of operators'
radiation doses during hepatobiliary fluoroscopic guided procedures. In addition,
patient dose in these procedures was also documented. MATERIALS AND METHODS: A
total of 283 transarterial chemoembolisation (TACE) and 302 biliary procedures,
including 52 percutaneous transhepatic cholangiogram (PTC), 36 bilioplasty and
214 biliary catheter changes (BCC) performed over 14 months, were included.
Electronic personal dosimeters were used to measure operator radiation doses.
Effective dose (E) was calculated using modified Niklason algorithm. Patient dose
was measured as dose area product (DAP) and fluoroscopy time (FT). RESULTS: For
TACE, E for radiologist ranged between 0 and 9.96 uSv, for radiographer 0-0.99
uSv and for nurse 0-4.65 uSv. The patient DAP and FT ranged between 1.5 and 421.9
Gy cm2 and 1.91-67.25 min. For PTC, E for the radiologist ranged between 0.33 and
55.89 uSv, for radiographer 0-38.61 uSv and for nurse 0-3.18 uSv. Patient DAP and
FT ranged between 1.7 and 218.4 Gy cm2 and 2.07-71.53 min. For bilioplasty, E
ranged between 0.09 and 9.24 uSv for radiologist, 0-0.84 uSv for radiographer and
0-1.38 uSv for nurse. The patients' DAP and FT ranged from 0.7 to 52.54 Gy cm2
and 1.13-24.47 min. For BCC, E ranged from 0 to 12.78 uSv for radiologist, 0-8.43
uSv for radiographer and 0-4.05 uSv for nurse. Patient DAP and FT ranged between
0.12 and 117.3 Gy cm2 and 0.57-15.83 min. CONCLUSIONS: This study shows that
doses to all operators performing hepatobiliary interventional procedures can be
very low.
PMID- 29344711
TI - Adult 'PICC' Device May be Used as a Tunnelled Central Venous Catheter in
Children.
AB - PURPOSE: Central venous access in children, in particular small children and
infants, is challenging. We have developed a technique employing adult
peripherally inserted central venous catheters (PICCs) as tunnelled central
venous catheters (TCVCs) in children. The principal advantage of this novel
technique is that the removal technique is less complex than that of conventional
cuffed TCVCs. The catheter can be removed simply by being pulled out and does not
require general anaesthesia. The purpose of this study is to determine the
success, safety and utility of this technique and to identify the rate of late
complications. We describe the 6-year experience in our unit. MATERIALS AND
METHODS: Electronic and paper medical records were reviewed for consecutive
paediatric patients who had a PICC device inserted as a TCVC over a 6-year period
(September 2009 through July 2015). The following data were recorded-patient
demographics, setting for PICC as TCVC insertion, use of ultrasound and
fluoroscopy, PICC device type, early or late complications and date of and reason
for removal. RESULTS: Twenty-one PICCs were inserted as TCVCs in 19 children, all
aged less than 10 years. Mean patient age at the time of placement was 3.7 years.
Average patient weight was 15.7 kg. All insertions were successful with no
significant immediate complications recorded. The most common indication for
insertion in our patient sample was pseudo-obstruction secondary to
gastrointestinal dysmotility disorder (24%), with cystic fibrosis infective
exacerbation being the second most frequent diagnosis (14%). Suspected catheter
related infection led to early device removal in one case (4.8%). Inadvertent
dislodgement occurred in one case (4.8%). Nineteen of the 21 devices (90.4%)
lasted for the total intended duration of use. CONCLUSION: Using a PICC device as
a TCVC in small children appears to be a safe technique, with an acceptable
complication profile.
PMID- 29344714
TI - Angiographic Anatomy and Relevance of 3 and 9 O'clock Arteries During
Radioembolization.
AB - PURPOSE: 3 and 9 o'clock arteries (3&9As) which supply the common hepatic duct
connect hepatic with duodenal/pancreatic territories. The study purpose is to
describe the angiographic anatomy of 3&9As and discuss their relevance when
performing radioembolization (RE) of liver malignancies. MATERIALS AND METHODS:
The anatomy of the 3&9As was systematically investigated by a retrospective
analysis of angiograms, technetium Tc-99 m-macroaggregated albumin (MAA)
scintigrams, yttrium-90 (Y90) Bremsstrahlung-SPECT/CT datasets, and clinical data
of 153 patients who underwent RE between 2010 and 2013. RESULTS: Analysis of
preprocedural angiograms identified 3&9As in 36 (24%) of the 153 patients.
Following embolization of the gastroduodenal artery, 3&9As were seen in 53 cases
(35%). The three most common origins of the 3&9As were the right hepatic artery
(n = 14), the cystic artery (n = 11), and S5 and S6 segmental arteries (n = 5
each). Extrahepatic Tc-99 m-MAA deposition in the territory of the 3&9As was
significantly more frequent when 3&9As were detectable on preprocedural
angiograms (28%visible vs. 11%not visible; p = 0.001) and especially when the
3&9As were not embolized or bridged prior to RE (50%not occluded/bridged vs.
19%occupied/bridged; p = 0.043). The presence of extrahepatic Y90 Bremsstrahlung
after RE (n = 17) was attributable to microsphere diversion via the 3&9A
territory in four patients and possible diversion via this territory in nine
patients. Five of these 13 patients presented with epigastric pain, nausea, or
vomiting (CTCAE severity grade <= 3) (p = 0.014). CONCLUSION: 3&9As are commonly
detectable during evaluation angiography prior to RE, have a variable
angioanatomic origin, and should be prophylactically occluded to prevent
complications.
PMID- 29344713
TI - Prognostic Factors in Overall Survival of Patients with Unresectable Intrahepatic
Cholangiocarcinoma Treated by Means of Yttrium-90 Radioembolization: Results in
Therapy-Naive Patients.
AB - INTRODUCTION: To investigate prognostic factors in unresectable intrahepatic
cholangiocarcinoma (ICC) therapy-naive patients after yttrium-90 (Y-90)
radioembolization (RE) therapy. MATERIALS AND METHODS: Between 2005 and 2016, 21
patients with ICC were treated with Y-90 RE only and their survival data were
analyzed. Patients were stratified and response was assessed by the Response
Evaluation Criteria in Solid Tumors (RECIST) criteria. RESULT: The overall median
survival was 15 months. Survival was significantly (p = 0.009) prolonged in
patients with tumor burden of <= 25% (n = 8, OS 37.5 months) versus those with a
tumor burden of 25-50% (n = 13, OS 15 months). The other variables: tumor
morphology (infiltrative vs. peripheral), tumor distribution (solitary vs.
multifocal), lobes involved (unilobar vs. bilobar), FDG PET status (FDG avid vs.
non-avid), RE treatment sessions (1 session vs. 2 sessions), metastases
(metastasis vs. no metastasis) and RECIST criteria, had no significant impact on
survival. CONCLUSION: Tumor burden represents a key prognostic factor of survival
in therapy-naive patients with unresectable ICC treated with Y-90 RE therapy
only.
PMID- 29344712
TI - Usefulness of Hydrogel-Coated Coils in Embolization of Pulmonary Arteriovenous
Malformations.
AB - PURPOSE: To evaluate the usefulness of hydrogel-coated coils for preventing
recanalization after coil embolization of pulmonary arteriovenous malformations
(PAVMs). MATERIALS AND METHODS: Thirty-seven consecutive patients with 57
untreated PAVMs underwent coil embolization with hydrogel-coated coils between
January 2013 and Jun 2017. The mean age was 49 years (range 9-83 years), and
there were seven male patients and 30 female patients. The median size of the
feeding artery was 3.7 mm (range 1.5-6.1 mm), and the median size of the venous
sac was 9.3 mm (range 2.6-36.6 mm). For all PAVM, embolization was attempted
using 0.018-in. hydrogel-coated coils with or without other coils (0.0135-0.018
in. bare platinum coils and fibered platinum coils). Technical success rate,
recanalization rate, and complications were evaluated. Technical success was
defined as completion of embolization using hydrogel-coated coils. Recanalization
was evaluated with time-resolved magnetic resonance angiography and/or pulmonary
angiography. RESULTS: In 56 of 57 PAVMs, embolization was successfully performed
with hydrogel-coated coils. Therefore, the technical success rate was 98%
(56/57). The number of PAVMs at risk was 56, 42, 18, and 12 at 0, 12, 24, and 36
months, respectively. There was no recanalization with a mean follow-up period of
19 months (range 2-47 months) in 56 PAVMs embolized with hydrogel-coated coils.
There were no major complications. As a minor complication, local pain was
observed in 8 of 43 sessions (19%) after embolization. CONCLUSIONS: Hydrogel
coated coils may be useful for preventing recanalization after the embolization
of PAVMs.
PMID- 29344715
TI - A Case of Stent Fracture After Transjugular Intrahepatic Portosystemic Shunt.
PMID- 29344716
TI - Safety and Effectiveness of Palliative Tunneled Peritoneal Drainage Catheters in
the Management of Refractory Malignant and Non-malignant Ascites.
AB - PURPOSE: To determine the safety and effectiveness of tunneled peritoneal
catheters in the management of refractory malignant and non-malignant ascites.
MATERIALS AND METHODS: An IRB-approved retrospective review was undertaken of
patients who underwent ultrasound and fluoroscopy-guided tunneled peritoneal
catheter placement for management of refractory malignant or non-malignant
ascites between January 1, 2009, and March 14, 2014. RESULTS: A total of 137
patients (76 M/61 F, mean age 62.9 years) underwent tunneled peritoneal catheter
placement for refractory malignant (N = 119; 86.9%) or non-malignant (N = 18;
13.1%) ascites. Technical success was 100% with no immediate complications.
Nineteen patients (13.9%) experienced a total of 11 minor and 12 major
complications. Nine patients developed a catheter-associated infection. The
remaining complications included leakage at the dermatotomy site (N = 8),
catheter dislodgement (N = 2), obstruction (N = 2), and groin pain (N = 2).
Patients who developed a catheter-associated infection had a significantly longer
catheter dwell time compared to those who did not develop an infection (median,
96.5 vs. 20 days; p < 0.01). Nine patients (6.6%) were lost to follow-up. Of the
remaining 128 patients, 125 died and the majority had a catheter in place (90.4%)
at the time of death. There was one catheter-associated death (bacterial
peritonitis; 0.8%). The median time from catheter placement to death was
significantly shorter in patients with malignant versus non-malignant ascites
(18.5 vs. 85 days; p < 0.0001). CONCLUSIONS: Tunneled peritoneal drainage
catheters are effective and relatively safe in the management of malignant and
non-malignant ascites. Longer catheter dwell time may be a risk factor for
catheter-associated infection, particularly in patients with a longer anticipated
survival in the palliative setting.
PMID- 29344717
TI - Multiple Enlarged Aneurysms in Primary Racemose Hemangioma of the Bronchial
Artery: Successful Prophylactic Transcatheter Arterial Embolization Using N-butyl
2-cyanoacrylate and Coils.
AB - An asymptomatic 48-year-old man presented with multiple aneurysms in a primary
racemose hemangioma of the right bronchial artery. Bronchial arteriography
revealed a tortuous artery with four fusiform aneurysms of varying sizes and
aneurysmal dilatation with marked thrombus formation in the long segment of the
distal portion. Because the tip of catheter could not pass beyond the aneurysmal
dilatation, we performed balloon-occluded embolization using a mixture of N-butyl
2-cyanoacrylate (NBCA) and iodized oil. For four other aneurysms, we performed
embolization using a coil alone or with NBCA. After 6 months, right bronchial
arteriography revealed no enhancement of the aneurysms. Despite the rarity of
this procedure, embolization with NBCA is a good option for bronchial artery
aneurysm embolization.
PMID- 29344718
TI - Combination of baseline FDG PET/CT total metabolic tumour volume and gene
expression profile have a robust predictive value in patients with diffuse large
B-cell lymphoma.
AB - PURPOSE: This study evaluated the predictive significance of total metabolic
tumour volume (TMTV) measured on baseline FDG PET/CT and its value in addition to
gene expression profiling using a new method of gene analysis (rapid reverse
transcriptase multiplex ligation-dependent probe amplification assay, RT-MLPA) in
patients with diffuse large B-cell lymphoma treated with R-CHOP or R-CHOP-like
chemotherapies. METHODS: The analysis included 114 patients. TMTV was measured
using a 41% SUVmax threshold and tumours were classified into GCB or ABC subtypes
according to the RT-MLPA assay. RESULTS: The median follow-up was 40 months. the
5-year progression-free survival (PFS) was 54% and the 5-year overall survival
(OS) was 62%. The optimal TMTV cut-off value was 261 cm3. In 59 patients with a
high TMTV the 5-year PFS and OS were 37% and 39%, respectively, in comparison
with 72% and 83%, respectively, in 55 patients with a low TMTV (p = 0.0002 for
PFS, p < 0.0001 for OS). ABC status was significantly associated with a worse
prognosis. TMTV combined with molecular data identified three groups with very
different outcomes: (1) patients with a low TMTV whatever their phenotype (n =
55), (2) patients with a high TMTV and GCB phenotype (n = 33), and (3) patients
with a high TMTV and ABC phenotype (n = 26). In the three groups, 5-year PFS
rates were 72%, 51% and 17% (p < 0.0001), and 5-year OS rates were 83%, 55% and
17% (p < 0.0001), respectively. In multivariate analysis, TMTV, ABC/GCB phenotype
and International Prognostic Index were independent predictive factors for both
PFS and OS (p < 0.05 for both). CONCLUSIONS: This integrated risk model could
lead to more accurate selection of patients that would allow better
individualization of therapy.
PMID- 29344719
TI - Phosphorylation of vasodilator-stimulated phosphoprotein contributes to
myocardial ischemic preconditioning.
AB - Ischemic preconditioning (IP) is a well-known strategy to protect organs against
cell death following ischemia. The previous work has shown that vasodilator
stimulated phosphoprotein (VASP) is involved in cytoskeletal reorganization and
that it holds significant importance for the extent of myocardial ischemia
reperfusion injury. Yet, the role of VASP during myocardial IP is, to date, not
known. We report here that VASP phosphorylation at serine157 and serine239 is
induced during hypoxia in vitro and during IP in vivo. The preconditioning
induced VASP phosphorylation inactivates the GP IIb/IIIa integrin receptor on
platelets, which results in the reduced formation of organ compromising platelet
neutrophil complexes. Experiments in chimeric mice confirmed the importance of
VASP phosphorylation during myocardial IP. When studying this in VASP-/- animals
and in an isolated heart model, we were able to confirm the important role of
VASP on myocardial IP. In conclusion, we were able to show that IP-induced VASP
phosphorylation in platelets is a protective mechanism against the deleterious
effects of ischemia.
PMID- 29344720
TI - Characteristics of pericytes in diethylstilbestrol (DES)-induced pituitary
prolactinoma in rats.
AB - Prolactinomas are the most common tumor of the human pituitary. They result in
excessive prolactin secretion and important changes in the vasculature. Pericytes
are perivascular cells associated with capillaries and have crucial roles in
physiological and pathological neovascularization. We previously reported that
pericytes produce type I and III collagens in the anterior pituitary of adult
rats. In addition, pituitary pericytes contained well-developed cell organelles
and actively synthesized collagens during early postnatal development. However,
the characteristics of pericytes in pituitary tumors are unclear. In this study,
we used diethylstilbestrol (DES)-treated rats as an animal model of prolactinoma.
Using five common pericyte markers, more pericytes were observed in rats treated
with DES for 3 months (prolactinoma) compared to the control. Transmission
electron microscopy revealed that attached and semidetached pericytes exhibited
active cell organelles. Moreover, we identified pericyte migration between
capillaries. Although the fine structure of pituitary pericytes was active in
prolactinoma, expressions of type I and III collagen mRNAs were greatly
diminished. In sum, the characteristics and functions of pericytes were altered
in pituitary tumors. This study is the first to clarify fine structural changes
of pericytes in rat prolactinomas and improves our understanding of the function
of pericytes under pathological conditions.
PMID- 29344721
TI - Post-mortem MR angiography: quantitative investigation and intravascular
retention of perfusates in ex situ porcine hearts.
AB - As the implementation of minimally invasive imaging techniques in both forensic
and pathological practice increases, research in this area focuses on addressing
recognised diagnostic weaknesses of current approaches. Assessment of sudden
cardiac death (SCD) can be considered one such area in which post-mortem imaging
still shows diagnostic weaknesses. We hypothesise that magnetic resonance imaging
(MRI) with an angiographic adjunct may improve the visualisation and
interpretation of cardiac pathologies in a post-mortem setting. To systematically
investigate this hypothesis, selected perfusates (paraffin oil, Gadovist(r);
doped physiological solution and polyethylene glycol (PEG)) were injected into
the left anterior descending (LAD) artery of ex situ porcine hearts to assess the
visualisation of perfusates in MRI as well as their intravascular retention over
12 h. Morphological images were acquired and quantitative T1 maps were generated
from inversion recovery data. Visualisation of vascular structure and image
quality were assessed using signal-to-noise and contrast-to-noise ratios.
Intravascular retention was assessed both visually and statistically using a
volume of interest (VOI) approach to analyse significant changes in signal
intensity in and around the filled LAD artery, as well as changes in the
longitudinal relaxation time (T1) in adjacent myocardium. In addition to
presenting possible mechanisms explaining perfusate extravasation given the
increased permeability of post-mortem vessels, the potential diagnostic
consequences of this phenomenon and the importance of contrast stability and
extended intravascular retention are discussed. In light of our findings and
these considerations, paraffin oil emerged as the preferred perfusate for use in
post-mortem MR angiography.
PMID- 29344722
TI - Benefit of the addition of hormone therapy to neoadjuvant anthracycline-based
chemotherapy for breast cancer: comparison of predicted and observed pCR.
AB - INTRODUCTION: Neoadjuvant hormonal therapy is generally considered a valid option
for hormone receptor positive breast cancer (BC) patients who are unfit for
chemotherapy or surgery. AIMS: Whilst numerous studies analyzed efficacy of
neoadjuvant chemotherapy (CT) or endocrine therapy (HT) alone in hormone receptor
positive patients, there is a lack of research looking at the usefulness of a
preoperative combinatorial approach of CT and HT in this patient subgroup.
METHODS: Using a predictive model previously described in the literature,
developed to analyze the probability of benefit from preoperative chemotherapy,
we were able to compare pathological complete response (pCR) rates expected with
the use of CT alone with the pCR rates reported in a population of 192 patients
treated with the combination of tamoxifen plus anthracycline-based CT at Cremona
Hospital between 2003 and 2006. RESULTS: Even with a relatively small patient
population, this approach provided insightful information for the selection of
hormone receptor positive BC patients most likely to benefit from the use of
preoperative HT and CT in combination. Whilst no statistically significant
benefit was obtained with the addition of tamoxifen to neoadjuvant chemotherapy
in the entire population, or in any of the molecular stratification subgroups,
the analysis of the calibration curve showed that a combinatorial approach may
improve pCR in patients with luminal B tumors. More specific trials should be
designed to confirm our initial results. CONCLUSION: To the best of our
knowledge, this is the first report investigating the efficacy of the combination
of CT and HT in the neoadjuvant treatment of hormone receptor positive BC.
PMID- 29344724
TI - When the rhythm disappears and the mind keeps dancing: sustained effects of
attentional entrainment.
AB - Research has demonstrated that the human cognitive system allocates attention
most efficiently to a stimulus that occurs in synchrony with an established
rhythmic background. However, our environment is dynamic and constantly changing.
What happens when rhythms to which our cognitive system adapted disappear? We
addressed this question using a visual categorization task comprising emotional
and neutral faces. The task was split into three blocks of which the first and
the last were completed in silence. The second block was accompanied by an
acoustic background rhythm that, for one group of participants, was synchronous
with face presentations, and for another group was asynchronous. Irrespective of
group, performance improved with background stimulation. Importantly, improved
performance extended into the third silent block for the synchronous, but not for
the asynchronous group. These data suggest that attentional entrainment resulting
from rhythmic environmental regularities disintegrates only gradually after the
regularities disappear.
PMID- 29344723
TI - Structural associations between organelle membranes in nectary parenchyma cells.
AB - MAIN CONCLUSION: The close association between membranes and organelles, and the
intense chloroplast remodeling in parenchyma cells of extrafloral nectaries
occurred only at the secretion time and suggest a relationship with the nectar
secretion. Associations between membranes and organelles have been well
documented in different tissues and cells of plants, but poorly explored in
secretory cells. Here, we described the close physical juxtaposition between
membranes and organelles, mainly with chloroplasts, in parenchyma cells of
Citharexylum myrianthum (Verbenaeceae) extrafloral nectaries under transmission
electron microscopy, using conventional and microwave fixation. At the time of
nectar secretion, nectary parenchyma cells exhibit a multitude of different
organelle and membrane associations as mitochondria-mitochondria, mitochondria
endoplasmic reticulum, mitochondria-chloroplast, chloroplast-nuclear envelope,
mitochondria-nuclear envelope, chloroplast-plasmalemma, chloroplast-chloroplast,
chloroplast-tonoplast, chloroplast-peroxisome, and mitochondria-peroxisome. These
associations were visualized as amorphous electron-dense material, a network of
dense fibrillar material and/or dense bridges. Chloroplasts exhibited protrusions
variable in shape and extension, which bring them closer to each other and to
plasmalemma, tonoplast, and nuclear envelope. Parenchyma cells in the pre- and
post-secretory stages did not exhibit any association or juxtaposition of
membranes and organelles, and chloroplast protrusions were absent. Chloroplasts
had peripheral reticulum that was more developed in the secretory stage. We
propose that such subcellular phenomena during the time of nectar secretion
optimize the movement of signaling molecules and the exchange of metabolites. Our
results open new avenues on the potential mechanisms of organelle contact in
parenchyma nectary cells, and reveal new attributes of the secretory cells on the
subcellular level.
PMID- 29344725
TI - Stimulating numbers: signatures of finger counting in numerosity processing.
AB - Finger counting is one of the first steps in the development of mature number
concepts. With a one-to-one correspondence of fingers to numbers in Western
finger counting, fingers hold two numerical meanings: one is based on the number
of fingers raised and the second is based on their ordinal position within the
habitual finger counting sequence. This study investigated how these two
numerical meanings of fingers are intertwined with numerical cognition in adults.
Participants received tactile stimulation on their fingertips of one hand and
named either the number of fingers stimulated (2, 3, or 4 fingers; Experiment 1)
or the number of stimulations on one fingertip (2, 3, or 4 stimulations;
Experiment 2). Responses were faster and more accurate when the set of stimulated
fingers corresponded to finger counting habits (Experiment 1) and when the number
of stimulations matched the ordinal position of the stimulated finger (Experiment
2). These results show that tactile numerosity perception is affected by
individual finger counting habits and that those habits give numerical meaning to
single fingers.
PMID- 29344726
TI - The safety and efficacy of elbasvir and grazoprevir in participants with
hepatitis C virus genotype 1b infection.
AB - BACKGROUND: Genotype 1b (GT1b) is the most common subtype of the hepatitis C
virus (HCV). We present an integrated analysis of 1070 participants with HCV GT1b
infection from 30 countries who received elbasvir/grazoprevir for 12 weeks.
METHODS: This is a retrospective analysis of data from participants with chronic
HCV GT1b infection enrolled in 11 phase II/III clinical trials. All participants
received elbasvir 50 mg plus grazoprevir 100 mg once daily for 12 weeks. The
primary end point of all studies was sustained virologic response 12 weeks after
completion of therapy (SVR12, HCV RNA < 15 IU/ml). RESULTS: SVR12 was 97.2%
(1040/1070). Of the 30 participants who failed to attain SVR12, 15 relapsed and
15 had nonvirologic failure. Among participant subgroups, SVR12 was high in those
with compensated cirrhosis (188/189, 99.5%), HIV co-infection (51/54, 94.4%), and
baseline viral load > 800,000 IU/ml (705/728, 96.8%). Resistance-associated
substitutions (RASs) at NS5A positions 28, 30, 31, or 93 were present in 21.6% of
participants at baseline. SVR12 was 99.6% (820/823) in participants without
baseline NS5A RASs and 94.7% (215/227) in those with baseline NS5A RASs. Serious
adverse events occurred in 3.2% (34/1070) of participants, nine of which occurred
after study medication was completed. CONCLUSIONS: Elbasvir/grazoprevir for 12
weeks represents an effective treatment option for participants with HCV GT1b
infection. SVR12 was high in all participant subgroups, including those with
compensated cirrhosis, HIV co-infection, and high baseline viral load.
CLINICALTRIALS. GOV IDENTIFIERS: The trials discussed in this paper were
registered with Clinicaltrial.gov as the following: NCT02092350 (C-SURFER),
NCT02105662 (C-EDGE Co-Infection), NCT02105467 (C-EDGE treatment-naive),
NCT02105701 (C-EDGE treatment-experienced), NCT01717326 (C-WORTHy), NCT02251990
(C-CORAL), NCT02105688 (C-EDGE COSTAR), NCT02252016 (C-EDGE IBLD), NCT02115321 (C
SALT), NCT02203149 (Japan phase 2/3 study), NCT02358044 (C-EDGE Head-2-Head).
PMID- 29344728
TI - [Cutaneous graft-versus-host disease].
AB - BACKGROUND: Graft-versus-host disease (GvHD) is a complex multiorgan disease,
which can occur as a complication following allogeneic stem cell transplantation.
Involvement of the skin represents the most common appearance of GvHD. The role
of the dermatologist is critical for diagnosis and initiation of treatment.
OBJECTIVES: The aim of this article is to provide a comprehensive review of the
cutaneous types of GvHD and to present the most recent data on diverse therapy
options for its acute and chronic form allowing the clinician to establish a
definite diagnosis and to initiate proper therapy. MATERIALS AND METHODS:
Possible clinical appearances and recommended criteria to assist in making the
right diagnosis are presented by means of expert recommendations. RESULTS AND
CONCLUSION: GvHD is still a complex entity whose diagnosis is often associated
with challenges due to its variable presentation. Proper diagnosis and subsequent
therapy is paramount for the optimal clinical outcome.
PMID- 29344727
TI - Work-related stress as a cardiovascular risk factor in police officers: a
systematic review of evidence.
AB - PURPOSE: Several studies suggest that work-related stress in police officers may
be associated with an increased risk of cardiovascular diseases. A systematic
review of studies is, however, still lacking. METHOD: According to PRISMA
statement, a systematic search of PubMed, ISI Web of Science, Cinahl and
PsychInfo electronic databases was undertaken. Studies published in English
between 1/1/2000 and 31/12/2016 were included. A studies quality assessment was
performed using the Newcastle Ottawa scale (NOS). RESULTS: The preliminary search
retrieved 752 records. After selection, 16 studies (total population 17,698) were
retrieved. The average quality of studies was low. Exposure to stress in cross
sectional studies was inconstantly associated with hypertension, obesity,
dyslipidaemia, and impaired glucose metabolism. In addition, there was a
prevalence of positive studies showing an association between stress and
cardiovascular disease morbidity. Studies of higher quality, such as longitudinal
studies on large sample size, were more supportive of a significant positive
association between stress and cardiovascular risk factors. Results were,
however, often conflicting and inconsistent with regard to definitions and
measurement of stress, features of individual study design, study conduct, and
conclusions drawn. CONCLUSIONS: A sound precautionary principle would be to adopt
worksite health promotion programs designed to implement stress management
strategies in this category of workers.
PMID- 29344730
TI - Skeletal dissemination in Paget's disease of the spine.
AB - PURPOSE: Paget's disease of bone (PDB) is a common skeletal disorder that is
associated with locally increased bone turnover, skeletal deformity and pain. We
report a case of skeletal dissemination in PDB of the spine. METHODS: Case
report. RESULTS: A 46-year-old former professional athlete suffered from
disseminated PDB throughout the spine and hips after various surgical
interventions including spondylodesis, bone grafting and bone morphogenetic
protein (rhBMP-2) administration. Only intravenous zoledronic acid prevented the
further progression of skeletal dissemination, which was expressed by a
normalization of (bone-specific) alkaline phosphatase levels. The biopsy obtained
from the lumbar spine confirmed the diagnosis of PDB in the absence of malignant
transformation. CONCLUSIONS: We outline skeletal dissemination as a possibly
surgery-related complication in a patient with PDB in the lumbar spine.
Bisphosphonates remain the treatment of first choice in PDB and surgical
interventions should be considered very carefully.
PMID- 29344729
TI - Sodium bicarbonate supplementation improves severe-intensity intermittent
exercise under moderate acute hypoxic conditions.
AB - Acute moderate hypoxic exposure can substantially impair exercise performance,
which occurs with a concurrent exacerbated rise in hydrogen cation (H+)
production. The purpose of this study was therefore, to alleviate this acidic
stress through sodium bicarbonate (NaHCO3) supplementation and determine the
corresponding effects on severe-intensity intermittent exercise performance.
Eleven recreationally active individuals participated in this randomised, double
blind, crossover study performed under acute normobaric hypoxic conditions (FiO2%
= 14.5%). Pre-experimental trials involved the determination of time to attain
peak bicarbonate anion concentrations ([HCO3-]) following NaHCO3 ingestion. The
intermittent exercise tests involved repeated 60-s work in their severe-intensity
domain and 30-s recovery at 20 W to exhaustion. Participants ingested either 0.3
g kg bm-1 of NaHCO3 or a matched placebo of 0.21 g kg bm-1 of sodium chloride
prior to exercise. Exercise tolerance (+ 110.9 +/- 100.6 s; 95% CI 43.3-178 s; g
= 1.0) and work performed in the severe-intensity domain (+ 5.8 +/- 6.6 kJ; 95%
CI 1.3-9.9 kJ; g = 0.8) were enhanced with NaHCO3 supplementation. Furthermore, a
larger post-exercise blood lactate concentration was reported in the experimental
group (+ 4 +/- 2.4 mmol l-1; 95% CI 2.2-5.9; g = 1.8), while blood [HCO3-] and pH
remained elevated in the NaHCO3 condition throughout experimentation. In
conclusion, this study reported a positive effect of NaHCO3 under acute moderate
hypoxic conditions during intermittent exercise and therefore, may offer an
ergogenic strategy to mitigate hypoxic induced declines in exercise performance.
PMID- 29344731
TI - The impact of surgeon volume on patient outcome in spine surgery: a systematic
review.
AB - PURPOSE: Recently, strategies aimed at optimizing provider factors have been
proposed, including regionalization of surgeries to higher volume centers and
adoption of volume standards. With limited literature promoting the
regionalization of spine surgeries, we undertook a systematic review to
investigate the impact of surgeon volume on outcomes in patients undergoing spine
surgery. METHODS: We performed a systematic review examining the association
between surgeon volume and spine surgery outcomes. To be included in the review,
the study population had to include patients undergoing a primary or revision
spinal procedure. These included anterior cervical discectomy and fusion (ACDF),
anterior/posterior cervical fusion, laminectomy/decompression, anterior/posterior
lumbar decompression with fusion, discectomy, and spinal deformity surgery (spine
arthrodesis). RESULTS: Studies were variable in defining surgeon volume
thresholds. Higher surgeon volume was associated with a significantly lower risk
of postoperative complications, a lower length of stay (LOS), lower cost of
hospital stay and a lower risk of readmissions and reoperations/revisions.
CONCLUSIONS: Findings suggest a trend towards better outcomes for higher volume
surgeons; however, further study needs to be carried out to define objective
volume thresholds for individual spine surgeries for surgeons to use as a marker
of proficiency.
PMID- 29344732
TI - Recognition of the importance of geogenic sources in the content of metals in
PM2.5 collected in the Mexico City Metropolitan Area.
AB - The study of airborne metals in urban areas is relevant due to their toxic
effects on human health and organisms. In this study, we analyzed metals
including rare earth elements (REE) in particles smaller than 2.5 MUm (PM2.5),
collected at five sites around the Mexico City Metropolitan Area (MCMA), during
three periods in 2011: April (dry-warm season, DW), August (rainy season, R), and
November (dry-cold season, DC). Principal component analysis allowed identifying
factors related to geogenic sources and factors related to anthropogenic sources.
The recognition of the high impact of geogenic sources in PM2.5 is in agreement
with the REE distribution patterns, which show similar behavior as those shown by
igneous rocks, confirming the influence of the regional geogenic material. Metals
associated to geogenic sources showed higher concentration (p < 0.05) at NE of
the MCMA and a significant correlation with prevalent winds. Geogenic metals show
similar seasonal distribution, with the highest concentration during DW (p <
0.05), suggesting a possible metal resuspension effect which affects more
significantly at lower relative humidity (RH). The metals associated with
anthropogenic sources are in agreement with the urban complexity of the area,
showing homogenous distribution throughout MCMA (p > 0.05) and no similar
seasonal pattern among them. These unexpected results exposed outstanding
information regarding the identification of different geogenic sources as the
main contributors of metals in the atmospheric environment in the MCMA and
highlighted the importance of meteorology in the spatial and seasonal metal
patterns.
PMID- 29344733
TI - Linking intraspecific trait variability and spatial patterns of subtropical
trees.
AB - The importance of intraspecific trait variability (ITV) to the spatial
distribution of individual species is unclear. We hypothesized that intraspecific
trait dispersions underlying niche processes deviate more from null model
expectations, by reducing their spread (range and variance), kurtosis, and
standard deviation of near-neighbor distance, for species with aggregated than
those with random distributions. The link between species' spatial distributions
and ITV patterns was examined using an individual tree-based trait data set, in
which specific leaf area, mean leaf area, leaf dry matter content, and diameter
at breast height were measured for 18,773 stems of 45 species in a 4.84 ha mapped
subtropical forest plot in China. The nearest-neighbor distance analysis showed
that, of 45 species, 14 species were distributed in random and 31 species were
distributed in aggregation, while no species was distributed in uniform in the
plot. The dispersions of all studied traits in species with an aggregated
distribution on average deviated more strongly from the null expectation than
those in species with a random distribution and that the extent of deviation was
negatively associated with the degree of spatial randomness across species. Our
results indicate that niche processes are primarily responsible for the spatial
structure of species with aggregated distributions, while stochastic processes
drive those with random distributions. Our results highlight the fundamental role
of ITV in shaping spatial patterns of co-existing species.
PMID- 29344734
TI - The level and extent of upper airway obstruction affects the severity of
laryngopharyngeal reflux.
PMID- 29344735
TI - Hydrochemistry and water quality of Rewalsar Lake of Lesser Himalaya, Himachal
Pradesh, India.
AB - The present research is to study hydrochemistry and water quality of Rewalsar
Lake during pre-monsoon, monsoon, and post-monsoon seasons. The Ca2+ and Na+ are
observed as the dominant cations from pre- to post-monsoon season. On the other
hand, HCO3- and Cl- are observed dominant anions during pre-monsoon and monsoon
seasons, whereas HCO3- and SO42- during post-monsoon season. The comparison of
alkaline earth metals with alkali metals and total cations (Tz+) has specified
that the carbonate weathering is the dominant source of major ions in the water
of lake. The HCO3- is noticed to be mainly originated from carbonate/calcareous
minerals during monsoon and post-monsoon, but through silicate minerals during
pre-monsoon. The SO42- in Rewalsar Lake is produced by the dissolution of
calcite and dolomite etc. The alkali metals and Cl- in the lake can be attributed
to the silicate weathering as well as halite dissolution and anthropogenic
activities. Certain other parameters like NO3-, NH4+, F-, and Br- are mainly a
result of anthropogenic activities. The alkaline earth metals are found to
surpass over alkali metals, whereas weak acid (HCO3-) exceed to strong acid (SO42
). The Piper diagram has shown Ca2+-HCO3- type of water during all the seasons.
The water quality index has indicated that the water quality of the lake is
unsuitable for drinking from pre- to post-monsoon. Several parameters like
salinity index, sodium adsorption ratio, sodium percent, residual sodium
carbonate, magnesium hazard etc. have revealed the water of Rewalsar Lake as
suitable for irrigation.
PMID- 29344736
TI - Predictors of analgesic efficacy of neurolytic celiac plexus block in patients
with unresectable pancreatic cancer: the importance of timing.
AB - BACKGROUND: Neurolytic celiac plexus block (NCPB) is a safe and effective method
for reducing abdominal cancer pain. However, the analgesic efficacy of NCPB is
not always guaranteed. The aim of this retrospective study was to identify
predictors for the analgesic efficacy of NCPB in patients with unresectable
pancreatic cancer. METHODS: Patients with unresectable pancreatic cancer who
underwent NCPB from 2006 to 2015 were enrolled. Good analgesia after NCPB was
defined as >= 50% reduction in pain score at day 30. Patient demographics, cancer
characteristics, and pain-related factors were evaluated using a logistic
regression analysis to identify predictors for good analgesia after NCPB.
Additionally, survival outcomes were compared between patients with poor and good
analgesia after NCPB. RESULTS: A total of 112 patients satisfied the study
protocol requirements. Forty-seven patients (41.9%) showed good analgesia after
NCPB. Better performance status, lower serum CA 19-9 level, shorter pain
duration, and lower opioid dose were observed in patients with good analgesia
after NCPB. Good performance status (ECOG performance status 1 vs. 2 or 3, OR =
2.737, 95% CI = 1.149 to 6.518, P = 0.023) and low daily opioid use (< 150 vs. >=
150 mg, OR = 2.813, 95% CI = 1.159 to 6.831, P = 0.022) before NCPB were
independent predictors of good analgesia after NCPB. The median survival was
significantly lower for patients with poor analgesia after NCPB (68 vs. 150 days,
P < 0.001). CONCLUSION: NCPB should be offered early to selected patients to
improve its analgesic efficacy in advance of deterioration from disease and pain
in this population.
PMID- 29344737
TI - The 125th anniversary of the His bundle discovery.
AB - In 1893, Wilhelm His Jr. was the first to describe the AV (atrioventricular)
bundle of the vertebrate heart, which now bears his name. Moreover, prior to the
turn of the century, W. His Jr. had proved the function of the AV bundle by
transection experiments in animals, and had interpreted Adams Stokes disease as
heart block due to pathological changes within the bundle. In this way, he was
ahead of his time. While clinical interest was limited to the bundle as the
location of an AV block in the first half of the 125 years, it has gained
attractiveness since then as a target of diagnostic and therapeutic procedures.
The introduction of His bundle electrography relaunched the interest in cardiac
arrhythmias. Once the AV bundle could be localized clinically, its ablation, and
in recent times its permanent stimulation, became options in the therapy of well
defined arrhythmia and conduction problems.
PMID- 29344738
TI - Genetic and functional analysis of the RYR1 mutation p.Thr84Met revealed a
susceptibility to malignant hyperthermia.
AB - PURPOSE: The aim of this study was to analyze the genetic and functional role of
a novel RYR1 variant c.251 C > T (p.Thr84Met) identified in a patient with muscle
weakness demonstrating MH susceptibility. METHODS: DNA testing of family members
was conducted for assessment of pathogenicity of the genetic variant. For
functional analysis, Ca2+ measurement using patient-derived myotubes and
p.Thr84Met RYR1-transfected human embryonic kidney (HEK)-293 cells was performed
to evaluate reactivity to RYR1 activators. The half-maximal effective
concentration (EC50) values of two RYR1 activators, caffeine and 4-chloro-m
cresol (4CmC), were calculated from the acquired dose-response curves. The EC50
was compared between two groups: for myotubes, the control group and the patient,
and for HEK-293 cells, WT and p.Thr84Met. RESULTS: Dose-response curves for
caffeine and 4CmC were shifted to the left in both myotubes and HEK-293 cells
compared to controls. The 50% effective concentration values for caffeine and
4CmC were significantly lower in both myotubes and HEK-293 cells compared to
controls (P < 0.001 for all comparisons). CONCLUSIONS: Our results of functional
testing indicated RYR1 hypersensitivity to caffeine and 4CmC. We conclude that
the genetic variant was associated with MH susceptibility.
PMID- 29344739
TI - What We Have Learned from the Recent Meta-analyses on Diagnostic Methods for
Atherosclerotic Plaque Regression.
AB - PURPOSE OF REVIEW: Atherosclerosis has major morbidity and mortality implications
globally. While it has often been considered an irreversible degenerative
process, recent evidence provides compelling proof that atherosclerosis can be
reversed. Plaque regression is however difficult to appraise and quantify, with
competing diagnostic methods available. Given the potential of evidence synthesis
to provide clinical guidance, we aimed to review recent meta-analyses on
diagnostic methods for atherosclerotic plaque regression. RECENT FINDINGS: We
identified 8 meta-analyses published between 2015 and 2017, including 79 studies
and 14,442 patients, followed for a median of 12 months. They reported on
atherosclerotic plaque regression appraised with carotid duplex ultrasound,
coronary computed tomography, carotid magnetic resonance, coronary intravascular
ultrasound, and coronary optical coherence tomography. Overall, all meta-analyses
showed significant atherosclerotic plaque regression with lipid-lowering therapy,
with the most notable effects on echogenicity, lipid-rich necrotic core volume,
wall/plaque volume, dense calcium volume, and fibrous cap thickness. Significant
interactions were found with concomitant changes in low density lipoprotein
cholesterol, high density lipoprotein cholesterol, and C-reactive protein levels,
and with ethnicity. Atherosclerotic plaque regression and conversion to a stable
phenotype is possible with intensive medical therapy and can be demonstrated in
patients using a variety of non-invasive and invasive imaging modalities.
PMID- 29344740
TI - Trends in Awareness and Use of HIV PrEP Among Gay, Bisexual, and Other Men who
have Sex with Men in Vancouver, Canada 2012-2016.
AB - Gay, bisexual, and other men who have sex with men (gbMSM) are at the highest
risk for HIV infection in British Columbia (BC). Pre-exposure prophylaxis (PrEP)
has been recently licensed but is currently not publicly funded in BC. Using
respondent-driven sampling, we recruited a cohort of gbMSM to complete a computer
assisted self-interview with follow-up every 6 months. Stratified by HIV status,
we examined trends in awareness of PrEP from 11/2012 to 02/2016 and factors
associated with PrEP awareness. 732 participants responded to the PrEP awareness
question. Awareness of PrEP among HIV-negative men increased from 18 to 80% (p <
0.0001 for trend); among HIV-positive men, awareness increased from 36 to 77% (p
< 0.0001). PrEP awareness was associated with factors related to HIV risk
including sero-adaptive strategies and sexual sensation seeking. Eight HIV
negative men reported using PrEP. Low PrEP uptake highlights that PrEP access
should be expanded for at-risk gbMSM in BC.
PMID- 29344741
TI - Assessment of potential risk factors for breast cancer in a population in
Southern Brazil.
AB - PURPOSE: The aim of this study is to assess potential risk factors for breast
cancer in a population in Southern Brazil and build a multivariate logistic model
using these factors for breast cancer risk prediction. METHODS: A total of 4242
women between 40 and 69 years of age without a history of breast cancer were
selected at primary healthcare facilities in Porto Alegre and submitted to
mammographic screening. They were evaluated for potential risk factors. RESULTS:
In all, 73 participants among the 4242 women had a breast cancer diagnosis during
the follow-up of the project (10 years). The multivariate analysis considering
all the patients aged 40-69 years showed that older age (OR 1.08, 95% CI 1.04
1.12), higher height (OR 1.04, 95% CI 1.01-1.09), and history of previous breast
biopsy (OR 2.66, 95% CI 1.38-5.13) were associated with the development of breast
cancer. Conversely, the number of pregnancies (OR 0.87, 95% CI 0.78-0.98) and use
of hormone replacement therapy (OR 0.39, 95% CI 0.20-0.75) were considered a
protective factor. Additionally, we performed an analysis separating the
participants into groups of 40-49 and 50-69 years old, since a risk factor could
have a specific behavior in these age groups. No additional risk factors were
identified within these age brackets, and some factors lost statistical
significance. CONCLUSION: The risk prediction model indicates that the following
variables should be assessed in this specific population: age, height, having had
previous breast biopsies, number of pregnancies, and use of hormone replacement
therapy. These findings may help to better understand the causal model of breast
cancer in Southern Brazil.
PMID- 29344742
TI - Increased Curie Temperature Induced by Orbital Ordering in
La0.67Sr0.33MnO3/BaTiO3 Superlattices.
AB - Recent theoretical studies indicated that the Curie temperature of perovskite
manganite thin films can be increased by more than an order of magnitude by
applying appropriate interfacial strain to control orbital ordering. In this
work, we demonstrate that the regular intercalation of BaTiO3 layers between
La0.67Sr0.33MnO3 layers effectively enhances ferromagnetic order and increases
the Curie temperature of La0.67Sr0.33MnO3/BaTiO3 superlattices. The preferential
orbital occupancy of eg(x 2 -y 2 ) in La0.67Sr0.33MnO3 layers induced by the
tensile strain of BaTiO3 layers is identified by X-ray linear dichroism
measurements. Our results reveal that controlling orbital ordering can
effectively improve the Curie temperature of La0.67Sr0.33MnO3 films and that in
plane orbital occupancy is beneficial to the double exchange ferromagnetic
coupling of thin-film samples. These findings create new opportunities for the
design and control of magnetism in artificial structures and pave the way to a
variety of novel magnetoelectronic applications that operate far above room
temperature.
PMID- 29344743
TI - Response to different furosemide doses predicts AKI progression in ICU patients
with elevated plasma NGAL levels.
AB - BACKGROUND: Furosemide responsiveness (FR) is determined by urine output after
furosemide administration and has recently been evaluated as a furosemide stress
test (FST) for predicting severe acute kidney injury (AKI) progression. Although
a standardized furosemide dose is required for FST, variable dosing is typically
employed based on illness severity, including renal dysfunction in the clinical
setting. This study aimed to evaluate whether FR with different furosemide doses
can predict AKI progression. We further evaluated the combination of an AKI
biomarker, plasma neutrophil gelatinase-associated lipocalin (NGAL), and FR for
predicting AKI progression. RESULTS: We retrospectively analyzed 95 patients who
were treated with bolus furosemide in our medical-surgical intensive care unit.
Patients who had already developed AKI stage 3 were excluded. A total of 18
patients developed AKI stage 3 within 1 week. Receiver operating curve analysis
revealed that the area under the curve (AUC) values of FR and plasma NGAL were
0.87 (0.73-0.94) and 0.80 (0.67-0.88) for AKI progression, respectively. When
plasma NGAL level was < 142 ng/mL, only one patient developed stage 3 AKI,
indicating that plasma NGAL measurements were sufficient to predict AKI
progression. We further evaluated the performance of FR in 51 patients with
plasma NGAL levels > 142 ng/mL. FR was associated with AUC of 0.84 (0.67-0.94)
for AKI progression in this population with high NGAL levels. CONCLUSIONS:
Although different variable doses of furosemide were administered, FR revealed
favorable efficacy for predicting AKI progression even in patients with high
plasma NGAL levels. This suggests that a combination of FR and biomarkers can
stratify the risk of AKI progression in a clinical setting.
PMID- 29344744
TI - Interleukin-1 receptor antagonist inhibits angiogenesis in gastric cancer.
AB - BACKGROUND: Interleukin-1 alpha (IL-1alpha) plays an important role in
tumorigenesis and angiogenesis of gastric cancer. The interleukin-1 receptor
antagonist (IL-1RA) inhibits IL-1 selectively and specifically through IL-1R type
I (IL-1RI). However, the underlying mechanism by which IL-1RA modulates the
interactions of tumor cells and their micro-environment is poorly understood. We
have evaluated the role of IL-1RA in the metastatic process as well as the mutual
or reciprocal actions between gastric cancer cells and stromal cells. MATERIALS
AND METHODS: The expressions of IL-1alpha, vascular endothelial growth factor
(VEGF), and IL-1RI mRNA were determined by reverse transcriptase-PCR. The
regulatory effect of IL-1RA on the secretion of VEGF in human gastric cancer
cells and human umbilical vein endothelial cells (HUVECs) was detected by enzyme
linked immunosorbent assay. The effect of IL-1RA on metastatic potential was
evaluated using proliferation, invasion, and angiogenesis assays, respectively,
including in vitro co-culture system models consisting of tumor cells and stromal
cells that were used to detect invasion and angiogenesis. RESULTS: Interleukin
1alpha mRNA was detected in the higher liver metastatic gastric cell line MKN45.
IL-1alpha protein was expressed in MKN45 cells and in HUVECs. VEGF mRNA and
protein were detected in the three gastric cancer cell lines (MKN4, NUGC-4, and
AGS). Levels of VEGF secreted by gastric cancer cells and HUVECs appeared to be
reduced through the action of IL-1RA via IL-1RI in a dose-dependent manner (P <
0.01). IL-1RA significantly inhibited the proliferation and migration of HUVECs
(P < 0.01) and tube formation by HUVECs (P < 0.01), both in a dose-dependent
manner. Compared with HUVECs grown without cancer cells (control) or with NUGC-4
cells, tube formation by HUVECs was significantly enhanced by co-culture with
MKN45 cells (P < 0.01). The enhanced tube formation in the presence of MKN45
cells was inhibited by the addition of IL-1RA (P < 0.01). CONCLUSIONS: The IL-1RA
downregulated the metastatic potential of gastric cancer through blockage of the
IL-1alpha/VEGF signaling pathways. IL-1RA has the potential to play a role in the
treatment of gastric cancer.
PMID- 29344745
TI - Wet milling of large quantities of human excision adipose tissue for the
isolation of stromal vascular fraction cells.
AB - The isolation of stromal vascular fraction (SVF) cells from excised human adipose
tissue, for clinical or research purposes, implies the tedious and time consuming
process of manual mincing prior to enzymatic digestion. Since no efficient
alternative technique to this current standard procedure has been proposed so
far, the aim of this study was to test a milling procedure, using two simple,
inexpensive and commercially available manual meat grinders, to process large
amounts of adipose tissue. The procedure was assessed on adipose tissue
resections from seven human donors and compared to manual mincing with scalpels.
The processed adipose tissues were digested and the resulting SVF cells compared
in terms of number, clonogenicity and differentiation capacity. After 10 min of
processing, either device tested yielded on average sixfold more processed
material for subsequent cell isolation than manual mincing. The isolation yield
of SVF cells (isolated cells per ml of adipose tissue), their viability,
phenotype, clonogenicity and osteogenic/adipogenic differentiation capacity,
tested by production of mineralized matrix and lipid vacuoles, respectively, were
comparable. This new method is practical and inexpensive and represents an
efficient alternative to the current standard for large scale adipose tissue
resection processing. A device based on the milling principle could be embedded
within a streamlined system for isolation and clinical use of SVF cells from
adipose tissue excision.
PMID- 29344746
TI - Desvenlafaxine-Induced Interstitial Pneumonitis: A Case Report.
AB - A 52-year-old man developed interstitial pneumonitis during treatment with
desvenlafaxine for major depressive disorder. The man received desvenlafaxine at
50 mg for symptoms of depression 4 years earlier. Six months after a dose
increase to 100 mg, he developed bronchitic symptoms with mild, persistent
dyspnea. Investigations revealed a restrictive pattern on pulmonary function
testing, bilateral upper lobe reticular opacities with traction bronchiectasis on
radiology imaging, and end-stage interstitial fibrosis with honeycomb changes
consistent with chronic hypersensitivity pneumonitis on open lung biopsy. He was
diagnosed with drug-induced interstitial pneumonitis. Desvenlafaxine was
discontinued and the patient received prednisone and mycophenolate mofetil. The
patient had subsequent stability in the progression of his pulmonary disease
after 1 month. After 1 year of drug discontinuation and treatment, his disease
process remained, but without major progression. A Naranjo assessment score of 4
was obtained, indicating a possible relationship between the patient's adverse
drug reaction and his use of the suspect drug.
PMID- 29344747
TI - Healthcare-based on Cloud Electrocardiogram System: A Medical Center Experience
in Middle Taiwan.
AB - Electrocardiogram (ECG) as one of the best methods to measure irregular
heartbeats is a dispensable method for doctor to diagnose Acute Myocardial
Infarction (AMI) patients. Most medical centers in Taiwan implement the reduction
of Door to Balloon (D2B) time, which is defined as the time interval starting
when an Acute-Myocardial-Infarction patient arrives at the Emergency Department,
and ending when a catheter guide wire crosses the culprit lesion as the acute
myocardial-infarction treatment on the patient in the cardiac catheterization
room. Generally, when a patient with acute-chest pain is sent into a hospital
(always to Emergency Department), the hospital will collect his/her ECG which
needs to be evaluated by a cardiologist to ensure that the patient really has
Acute Myocardial Infarction. Then the medical workers deliver the patient to the
cardiac catheterization room to operate balloon angioplasty. In previous years,
the cardiologist must utilize a PC to connect to the Intranet of the hospital and
employ a special PACS (Picture Archiving and Communication System) image browser
before he/she can check the patient's ECG. But this will prolong the D2B time
since the doctor may stay outdoors and he/she needs some time to find a PC and
network. Of course, if the PC has not installed the PACS image browser, the
doctor has to download and install it. Consequently, the D2B time should be
worsened, thus possibly impacting the patient's life. Therefore, in this paper,
we introduce a Cloud-based Electrocardiogram System, with which cardiologists can
directly utilize their smart phones to browse the patient's ECG so as to shorten
the D2B time. This system has been online in a medical center in middle Taiwan
for more than one year. The shortened D2B time is longer than 10 min, i.e.,
receiving fine results.
PMID- 29344748
TI - Lead sorption characteristics of various chicken bone part-derived chars.
AB - Recycling food waste for beneficial use is becoming increasingly important in
resource-limited economy. In this study, waste chicken bones of different parts
from restaurant industry were pyrolyzed at 600 degrees C and evaluated for char
physicochemical properties and Pb sorption characteristics. Lead adsorption
isotherms by different chicken bone chars were carried out with initial Pb
concentration range of 1-1000 mg L-1 at pH 5. The Pb adsorption data were better
described by the Langmuir model (R2 = 0.9289-0.9937; ARE = 22.7-29.3%) than the
Freundlich model (R2 = 0.8684-0.9544; ARE = 35.4-72.0%). Among the chars derived
from different chicken bone parts, the tibia bone char exhibited the highest
maximum Pb adsorption capacity of 263 mg g-1 followed by the pelvis (222 mg g-1),
ribs (208 mg g-1), clavicle (179 mg g-1), vertebrae (159 mg g-1), and humerus
(135 mg g-1). The Pb adsorption capacities were significantly and positively
correlated with the surface area, phosphate release amount, and total phosphorus
content of chicken bone chars (r >= 0.9711). On the other hand, approximately 75
88% of the adsorbed Pb on the chicken bone chars was desorbable with 0.1 M HCl,
indicating their recyclability for reuse. Results demonstrated that chicken bone
char could be used as an effective adsorbent for Pb removal in wastewater.
PMID- 29344749
TI - Diagnosis of sleep apnea in patients with stable chronic heart failure using a
portable sleep test diagnostic device.
AB - PURPOSE: ApneaLink is a portable device for the screening of sleep apnea, a
prevalent and underdiagnosed comorbidity in heart failure patients. A prospective
cross-sectional study in patients with chronic heart failure was carried out to
assess the sensitivity and specificity of apnea-hypopnea index (AHI) measurements
using ApneaLink against the standard polysomnography test. METHODS: Adult
patients with a prior hospitalization in an acute heart failure hospital unit
were recruited for the study. All participants were tested for sleep apnea using
ApneaLink and polysomnography simultaneously during an overnight stay at a sleep
laboratory. Global sleep apnea was evaluated according to the AHI, which was
analyzed and compared. Subpopulation comparison based on ejection fraction was
not realized due to population size. RESULTS: Thirty-five patients with stable
chronic heart failure completed the study (mean age 70.9 +/- 10.5 years and body
mass index 30.0 +/- 4.7 kg/m2). Two patients were excluded due to insufficient
study duration. ApneaLink had a sensitivity greater than 80% for all AHI
measurements, and a specificity greater than 80% for all AHI measurements, except
for AHI >= 5 events/h (61.5%). The results showed higher sensitivities and
specificities at AHI values of >= 10 events/h (sensitivity 81.3% and specificity
84.2%) and >= 15 events/h (sensitivity 83.3% and specificity 91.3%). Correlation
analysis showed that AHI measurements using ApneaLink and polysomnography had a
strong and significant correlation (r = 0.794; P < 0.001). CONCLUSIONS: Our
results suggest that ApneaLink could be used in clinical practice to identify
heart failure patients with high (AHI >= 15 events/h) and low (AHI < 5 events/h)
probability of having sleep apnea, sparing the need for a diagnostic
polysomnography and thus potentially impacting prognosis by providing a more cost
effective and timely diagnosis of this non-cardiac comorbidity.
PMID- 29344751
TI - Associations Between Early Intervention Home Visits, Family Relationships and
Competence for Mothers of Children with Developmental Disabilities.
AB - Objectives To examine the association between intensity of home visits in early
intervention (EI), perceived helpfulness of home visits in EI, and positive
family relationships as predictors of maternal competence at age 3, as well as
moderating effects of predictors, controlling for child characteristics, family
demographics, and negative life events. Methods Data were drawn from the Early
Intervention Collaborative Study (EICS), a 24-year longitudinal investigation of
approximately 190 families of children with developmental disabilities who
participated in EI programs in Massachusetts and New Hampshire. The primary
analytic strategy was multivariable regression modeling. Each independent
predictor was tested individually and then all together to build the final model.
Interactions between independent predictors were also examined. Results After
controlling for child and family characteristics and negative life events, the
intensity of home visits was not significantly associated with maternal
competence at age 3. However, the helpfulness of home visits (beta = 2.94, S.E. =
1.12, p < .01) and positive family relationships (beta = 5.11, S.E. = 1.08, p <
.001) were associated with higher maternal competence when the child was 3 years
old. Conclusions for Practice Recommendations for programs and policy include
collecting life course data on families, particularly on their family
relationships and experiences in EI and home visiting, assessing family
relationships at the beginning of EI using a strengths-based perspective, and
closely monitoring the quality of services.
PMID- 29344750
TI - Physical Activity and Consumption Patterns of Reproductive-Aged Women by BMI
Category.
AB - Objectives Obesity before and during pregnancy is associated with adverse effects
for mother and child, but little is known about physical activity and consumption
patterns among reproductive-aged women. The goal of this study is to identify
behaviors of nonpregnant reproductive-aged women associated with normal weight,
overweight, and obesity. Methods Data from the nationally representative National
Eating Trends survey (2003-2011) were analyzed, comparing number of days of
exercise in a 1-week period and consumption of fruits/vegetables, sugar sweetened
beverages (SSB), and concentrated sweets by BMI. Behaviors were compared using
analysis of variance and Chi square test across groups. Ordinal logistic
regression was used to compare behaviors across groups controlling for
demographic factors. Multivariable Poisson regression was used to identify
demographic factors associated with behaviors among obese women. Results Among
5941 18-45-year-old women, exercise and fruit/vegetable consumption were
associated with healthy weight controlling for demographic factors. Reporting any
exercise or fruit/vegetable consumption was associated with decreased odds of
overweight or obesity (aOR 0.73, 95% CI 0.64-0.83 and aOR 0.74, 95% CI 0.58-0.95,
respectively). Consuming SSBs was associated with increasing BMI category while
consuming concentrated sweets was unexpectedly associated with normal weight.
Among obese women, being on any diet was associated with increased exercise
frequency and fruit/vegetable consumption and decreased SSB consumption.
Conclusions for Practice Physical activity and consumption behaviors are
associated with weight among reproductive-aged women in ways similar to those in
the general population. Promoting exercise and fruit/vegetable consumption has
the potential to reduce obesity.
PMID- 29344752
TI - Transforming Dermatologic Imaging for the Digital Era: Metadata and Standards.
AB - Imaging is increasingly being used in dermatology for documentation, diagnosis,
and management of cutaneous disease. The lack of standards for dermatologic
imaging is an impediment to clinical uptake. Standardization can occur in image
acquisition, terminology, interoperability, and metadata. This paper presents the
International Skin Imaging Collaboration position on standardization of metadata
for dermatologic imaging. Metadata is essential to ensure that dermatologic
images are properly managed and interpreted. There are two standards-based
approaches to recording and storing metadata in dermatologic imaging. The first
uses standard consumer image file formats, and the second is the file format and
metadata model developed for the Digital Imaging and Communication in Medicine
(DICOM) standard. DICOM would appear to provide an advantage over using consumer
image file formats for metadata as it includes all the patient, study, and
technical metadata necessary to use images clinically. Whereas, consumer image
file formats only include technical metadata and need to be used in conjunction
with another actor-for example, an electronic medical record-to supply the
patient and study metadata. The use of DICOM may have some ancillary benefits in
dermatologic imaging including leveraging DICOM network and workflow services,
interoperability of images and metadata, leveraging existing enterprise imaging
infrastructure, greater patient safety, and better compliance to legislative
requirements for image retention.
PMID- 29344753
TI - Comparative Approach of MRI-Based Brain Tumor Segmentation and Classification
Using Genetic Algorithm.
AB - The detection of a brain tumor and its classification from modern imaging
modalities is a primary concern, but a time-consuming and tedious work was
performed by radiologists or clinical supervisors. The accuracy of detection and
classification of tumor stages performed by radiologists is depended on their
experience only, so the computer-aided technology is very important to aid with
the diagnosis accuracy. In this study, to improve the performance of tumor
detection, we investigated comparative approach of different segmentation
techniques and selected the best one by comparing their segmentation score.
Further, to improve the classification accuracy, the genetic algorithm is
employed for the automatic classification of tumor stage. The decision of
classification stage is supported by extracting relevant features and area
calculation. The experimental results of proposed technique are evaluated and
validated for performance and quality analysis on magnetic resonance brain
images, based on segmentation score, accuracy, sensitivity, specificity, and dice
similarity index coefficient. The experimental results achieved 92.03% accuracy,
91.42% specificity, 92.36% sensitivity, and an average segmentation score between
0.82 and 0.93 demonstrating the effectiveness of the proposed technique for
identifying normal and abnormal tissues from brain MR images. The experimental
results also obtained an average of 93.79% dice similarity index coefficient,
which indicates better overlap between the automated extracted tumor regions with
manually extracted tumor region by radiologists.
PMID- 29344754
TI - Green and Sustainable Separation of Natural Products from Agro-Industrial Waste:
Challenges, Potentialities, and Perspectives on Emerging Approaches.
AB - New generations of biorefinery combine innovative biomass waste resources from
different origins, chemical extraction and/or synthesis of biomaterials,
biofuels, and bioenergy via green and sustainable processes. From the very
beginning, identifying and evaluating all potentially high value-added chemicals
that could be removed from available renewable feedstocks requires robust,
efficient, selective, reproducible, and benign analytical approaches. With this
in mind, green and sustainable separation of natural products from agro
industrial waste is clearly attractive considering both socio-environmental and
economic aspects. In this paper, the concepts of green and sustainable separation
of natural products will be discussed, highlighting the main studies conducted on
this topic over the last 10 years. The principal analytical techniques (such as
solvent, microwave, ultrasound, and supercritical treatments), by-products (e.g.,
citrus, coffee, corn, and sugarcane waste) and target compounds (polyphenols,
proteins, essential oils, etc.) will be presented, including the emerging green
and sustainable separation approaches towards bioeconomy and circular economy
contexts.
PMID- 29344755
TI - Mathematical modelling of bone adaptation of the metacarpal subchondral bone in
racehorses.
AB - In Thoroughbred racehorses, fractures of the distal limb are commonly
catastrophic. Most of these fractures occur due to the accumulation of fatigue
damage from repetitive loading, as evidenced by microdamage at the predilection
sites for fracture. Adaptation of the bone in response to training loads is
important for fatigue resistance. In order to better understand the mechanism of
subchondral bone adaptation to its loading environment, we utilised a square root
function defining the relationship between bone volume fraction [Formula: see
text] and specific surface [Formula: see text] of the subchondral bone of the
lateral condyles of the third metacarpal bone (MCIII) of the racehorse, and using
this equation, developed a mathematical model of subchondral bone that adapts to
loading conditions observed in vivo. The model is expressed as an ordinary
differential equation incorporating a formation rate that is dependent on strain
energy density. The loading conditions applied to a selected subchondral region,
i.e. volume of interest, were estimated based on joint contact forces sustained
by racehorses in training. For each of the initial conditions of [Formula: see
text] we found no difference between subsequent homoeostatic [Formula: see text]
at any given loading condition, but the time to reach equilibrium differed by
initial [Formula: see text] and loading condition. We found that the observed
values for [Formula: see text] from the mathematical model output were a good
approximation to the existing data for racehorses in training or at rest. This
model provides the basis for understanding the effect of changes to training
strategies that may reduce the risk of racehorse injury.
PMID- 29344757
TI - Should we stop anti-thrombotic agents prior to vitrectomy?
PMID- 29344756
TI - The Current State of Left Main Percutaneous Coronary Intervention.
AB - PURPOSE OF REVIEW: While coronary artery bypass grafting (CABG) remains the
standard of care, advances in stenting technology and procedural technique are
changing the role of percutaneous coronary intervention (PCI) in the treatment of
severe left main coronary artery (LMCA) disease. We review contemporary evidence
comparing PCI and CABG for the treatment of severe LMCA disease, discuss optimal
techniques during left main PCI, and provide guidance on studied
revascularization strategies within specific patient subgroups. RECENT FINDINGS:
Results from randomized control trials of patients treated with PCI or CABG for
severe LMCA disease demonstrate comparable short- and mid-term rates of death,
myocardial infarction (MI), and stroke, but increased rates of repeat or target
vessel revascularization after PCI. Though extended follow-up data has suggested
lower long-term rates of MI and stroke in patients with severe LMCA disease
treated with CABG, results from patients undergoing PCI with second-generation
drug-eluting stents (DES) demonstrate non-inferiority in these outcomes. These
findings are generalizable to patients with severe LMCA disease having low to
intermediate anatomic complexity. Intravascular ultrasound and double kissing
(DK) crush stenting also reduce adverse event rates among patients undergoing
left main PCI and improve long-term outcomes. In patients with severe LMCA
disease having low to intermediate anatomic complexity, both CABG and PCI with
second-generation DES are effective methods of revascularization with comparable
long-term rates of death, MI, and stroke. The roles of multi-vessel coronary
artery disease and anatomic complexity on long-term outcomes after CABG or PCI
for severe LMCA disease remain under investigation.
PMID- 29344758
TI - Temperature Dependence of Raman-Active In-Plane E2g Phonons in Layered Graphene
and h-BN Flakes.
AB - Thermal properties of sp2 systems such as graphene and hexagonal boron nitride (h
BN) have attracted significant attention because of both systems being excellent
thermal conductors. This research reports micro-Raman measurements on the in
plane E2g optical phonon peaks (~ 1580 cm-1 in graphene layers and ~ 1362 cm-1 in
h-BN layers) as a function of temperature from - 194 to 200 degrees C. The h-BN
flakes show higher sensitivity to temperature-dependent frequency shifts and
broadenings than graphene flakes. Moreover, the thermal effect in the c direction
on phonon frequency in h-BN layers is more sensitive than that in graphene layers
but on phonon broadening in h-BN layers is similar as that in graphene layers.
These results are very useful to understand the thermal properties and related
physical mechanisms in h-BN and graphene flakes for applications of thermal
devices.
PMID- 29344759
TI - Mathematical Model of Contractile Ring-Driven Cytokinesis in a Three-Dimensional
Domain.
AB - In this paper, a mathematical model of contractile ring-driven cytokinesis is
presented by using both phase-field and immersed-boundary methods in a three
dimensional domain. It is one of the powerful hypotheses that cytokinesis happens
driven by the contractile ring; however, there are only few mathematical models
following the hypothesis, to the author's knowledge. I consider a hybrid method
to model the phenomenon. First, a cell membrane is represented by a zero-contour
of a phase-field implicitly because of its topological change. Otherwise,
immersed-boundary particles represent a contractile ring explicitly based on the
author's previous work. Here, the multi-component (or vector-valued) phase-field
equation is considered to avoid the emerging of each cell membrane right after
their divisions. Using a convex splitting scheme, the governing equation of the
phase-field method has unique solvability. The numerical convergence of
contractile ring to cell membrane is proved. Several numerical simulations are
performed to validate the proposed model.
PMID- 29344760
TI - On the Shapley Value of Unrooted Phylogenetic Trees.
AB - The Shapley value, a solution concept from cooperative game theory, has recently
been considered for both unrooted and rooted phylogenetic trees. Here, we focus
on the Shapley value of unrooted trees and first revisit the so-called split
counts of a phylogenetic tree and the Shapley transformation matrix that allows
for the calculation of the Shapley value from the edge lengths of a tree. We show
that non-isomorphic trees may have permutation-equivalent Shapley transformation
matrices and permutation-equivalent null spaces. This implies that estimating the
split counts associated with a tree or the Shapley values of its leaves does not
suffice to reconstruct the correct tree topology. We then turn to the use of the
Shapley value as a prioritization criterion in biodiversity conservation and
compare it to a greedy solution concept. Here, we show that for certain
phylogenetic trees, the Shapley value may fail as a prioritization criterion,
meaning that the diversity spanned by the top k species (ranked by their Shapley
values) cannot approximate the total diversity of all n species.
PMID- 29344761
TI - Construct Validity of the Autism Impact Measure (AIM).
AB - The Autism Impact Measure (AIM) was designed to track incremental change in
frequency and impact of core ASD symptoms. The current study examined the
structural and convergent validity of the AIM in a large sample of children with
ASD. The results of a series of exploratory and confirmatory factor analyses
yielded a final model with five theoretically and empirically meaningful
subdomains: Repetitive Behavior, Atypical Behavior, Communication, Social
Reciprocity, and Peer Interaction. The final model showed very good fit both
overall and for each of the five factors, indicating excellent structural
validity. AIM subdomain scores were significantly correlated with measures of
similar constructs across all five domains. The results provide further support
for the psychometric properties of the AIM.
PMID- 29344762
TI - Capsule commentary on James et al., Impact of a population health management
intervention on disparities in cardiovascular disease control.
PMID- 29344763
TI - Visual awareness negativity is an early neural correlate of awareness: A
preregistered study with two Gabor sizes.
AB - Electrophysiological recordings are commonly used to study the neural correlates
of consciousness in humans. Previous research is inconsistent as to whether
awareness can be indexed with visual awareness negativity (VAN) at about 200 ms
or if it occurs later. The present study was preregistered with two main aims:
First, to provide independent evidence for or against the presence of VAN, and
second, to study whether stimulus size may account for the inconsistent findings.
Subjects were shown low-contrast Gaussian filtered gratings (Gabor patches) in
the four visual quadrants. Gabor size (large and small) was varied in different
sessions and calibrated to each subject's threshold of visual awareness. Event
related potentials were derived from trials in which subjects localized the
Gabors correctly to capture the difference between trials in which they reported
awareness versus no awareness. Bayesian analyses revealed very strong evidence
for the presence of VAN for both Gabor sizes. However, there was no evidence for
or against an effect of stimulus size. The present findings provide evidence for
VAN as an early neural correlate of awareness.
PMID- 29344765
TI - Parent-child separation: the relationship between separation and psychological
adjustment among Chinese rural children.
AB - PURPOSE: The current study aimed to explore the characteristics of psychological
adjustment among Chinese left-behind children (LBC) in rural areas, and to
examine the association between separation duration from parent/parents (SDP) and
children's psychological adjustment and the extent to which personality mediates
this hypothesized link. METHODS: We surveyed 534 rural children and adolescents
aged 10-17 years at school (440 LBC and 94 non-LBC) in 2013, who were selected
for participation using stratified cluster sampling from two counties in
Chongqing, China. Measures used included socio-demographic variables, age at the
commencement and end of the separation from parents, the revised Chinese Juvenile
Eysenck Personality Questionnaire, and the Adolescent Psychological Adaptability
Scale. RESULTS: Most children (82.4%) had experienced separation from parents. t
test results showed a marginally significant difference (p = .08) in
psychological adjustment between LBC (mean = 64.44, SD = 8.62) and non-LBC (mean
= 66.16, SD = 9.26). LBC's mean SDP was 5.64 years (SD = 3.90). Correlation
analysis showed that children's SDP was negatively associated with psychological
adjustment. Structural equation modeling showed that neuroticism, but not
extraversion or psychoticism, fully mediated the link between children's SDP and
psychological adjustment. CONCLUSION: Personality (neuroticism) is one of the
mediating pathways through which long-term SDP may predict poor psychological
adjustment among children. Given the detrimental impact of long-term SDP,
interventions should target the mediating pathway to buffer against the negative
impact of parental separation on the affected rural children and to improve their
mental health.
PMID- 29344764
TI - O-GlcNAcylation: key regulator of glycolytic pathways.
AB - Elevated O-GlcNAcylation is emerging as a general characteristic of most cancers.
Although O-GlcNAcylation can regulate many cell biological pathways, recent
evidence suggests that it is a key regulator of metabolic pathways including
glycolysis in cancer cells. This review summarizes our current understanding of
how O-GlcNAcylation regulates glycolytic pathways and contributes to alterations
in cancer cell metabolism.
PMID- 29344766
TI - Patient-reported symptoms before palliative radiotherapy predict survival
differences.
AB - BACKGROUND: Widely used prognostic scores, e. g., for brain or bone metastases,
are based on disease- and patient-related factors such as extent of metastases,
age and performance status, which were available in the databases used to develop
the scores. Few groups were able to include patient-reported symptoms. In our
department, all patients were assessed with the Edmonton Symptom Assessment
System (ESAS, a one-sheet questionnaire addressing 11 major symptoms and
wellbeing on a numeric scale of 0-10) at the time of treatment planning since
2012. Therefore, we analyzed the prognostic impact of baseline ESAS symptom
severity. METHODS: Retrospective review of 102 patients treated with palliative
radiotherapy (PRT) between 2012 and 2015. All ESAS items were dichotomized
(below/above median). Uni- and multivariate analyses were performed to identify
prognostic factors for survival. RESULTS: The most common tumor types were
prostate, breast and non-small cell lung cancer, predominantly with distant
metastases. Median survival was 6 months. Multivariate analysis resulted in six
significant prognostic factors. These were ESAS pain while not moving (median 3),
ESAS appetite (median 5), Eastern Cooperative Oncology Group (ECOG) performance
status, pleural effusion/metastases, intravenous antibiotics at start or within 2
weeks before PRT and no systemic cancer treatment. CONCLUSIONS: Stronger pain
while not moving and reduced appetite (below/above median) predicted
significantly shorter survival. Development of new prognostic scores should
include patient-reported symptoms and other innovative parameters because they
were more important than primary tumor type, age and other traditional baseline
parameters.
PMID- 29344767
TI - Klotho attenuates isoproterenol-induced hypertrophic response in H9C2 cells by
activating Na+/K+-ATPase and inhibiting the reverse mode of Na+/Ca2+-exchanger.
AB - Cardiac hypertrophy plays a major role in heart failure and is related to patient
morbidity and mortality. Calcium overloading is a main risk for cardiac
hypertrophy, and Na+/K+-ATPase (NKA) has been found that it could not only
regulate intracellular Na+ levels but also control the intracellular Ca2+
([Ca2+]i) level through Na+/Ca2+-exchanger (NCX). Recent studies have reported
that klotho could affect [Ca2+]i level. In this study, we aimed at exploring the
role of klotho in improving isoproterenol-induced hypertrophic response of H9C2
cells. The H9C2 cells were randomly divided into control and isoproterenol (ISO)
(10 MUM) groups. Klotho protein (10 MUg/ml) or NKAalpha2 siRNA was used to
determine the changes in isoproterenol-induced hypertrophic response. The
alterations of [Ca2+]i level were measured by spectrofluorometry. Our results
showed that H9C2 cells which were treated with isoproterenol presented a higher
level of [Ca2+]i and hypertrophic gene expression at 24 and 48 h compared with
the control group. Moreover, the expressions of NKAalpha1 and NKAalpha2 were both
increased in control and ISO groups after treating with klotho protein;
meanwhile, the NKA activity was increased and NCX activity was decreased after
treatment. Consistently, the [Ca2+]i level and hypertrophic gene expression were
decreased in ISO group after klotho protein treatment. However, these effects
were both prevented by transfecting with NKAalpha2 siRNA. In conclusion, these
findings demonstrated that klotho inhibits isoproterenol-induced hypertrophic
response in H9C2 cells by activating NKA and inhibiting the reverse mode of NCX
and this effect may be associated with the upregulation of NKAalpha2 expression.
PMID- 29344768
TI - Diagnosis and Treatment of Injuries to the Biceps and Superior Labral Complex in
Overhead Athletes.
AB - PURPOSE OF REVIEW: This review discusses the diagnostic and treatment challenges
presented by injuries to the biceps and superior labral complex. RECENT FINDINGS:
A focused patient history, numerous physical examination maneuvers, and
appropriate advanced imaging studies must be utilized to reach an accurate
diagnosis. Nonoperative management, even in overhead athletes, has demonstrated
relatively good outcomes, while operative outcomes have yielded mixed results.
The surgeon must take into account a number of variables when choosing the
appropriate surgical procedure: labral repair versus biceps tenodesis.
Rehabilitation, either as nonoperative management or as a postoperative protocol,
should focus on restoring glenohumeral and scapulothoracic strength, endurance,
and full, pain-free range of motion, while correcting any deficiencies in balance
or rhythm throughout the overhead motion. Despite the operative treatment
challenges that SLAP tears present, with new techniques and proper patient
selection, overhead athletes with injuries to the biceps and superior labrum
complex can return to sport at a high level.
PMID- 29344770
TI - Sub-inner limiting membrane hemorrhage in a patient with Terson syndrome.
AB - PURPOSE: To report a case of bilateral Terson Syndrome with sub inner limiting
membrane hemorrhage associated with a rare finding: perimacular fold. METHODS:
The patient, a 34 years old female with aneurysmal subarachnoid hemorrhage and
bilateral Terson syndrome was admitted to the Ophthalmology department,
complaining of blurred vision. Core vitrectomy, hyaloid detachment, peeling of
the ILM and aspiration of the sub inner limiting membrane hemorrhage was
performed. Once the inner limiting membrane of the left eye was peeled off, we
noticed a particular aspect: the perimacular fold. RESULT: Although our patient
suffered from a massive vitreous haemorrhage the postoperative outcome was
favorable with a final best corrected visual acuity of 20/30. CONCLUSIONS: In
patients with billateral Terson syndrome we recommend early surgery, especially
if the neurological status allows it, a good visual acuity being helpful for the
neurophysical rehabilitation of the patient.
PMID- 29344769
TI - Sensitive Synchronous Spectrofluorimetric Study of Certain Sunscreens Using
Fluorescence Enhancers in Cosmeceutical Formulations.
AB - Synchronous spectrofluorimetric methods could be successfully adopted for
simultaneous determination of Octinoxate (OMC), Avobenzone (AVO), Octyltriazone
(OT), and Phenyl benzimidazole sulfonic acid (PBSA) in moisturizing sunscreen
lotion, utilizing beta-CD as fluorescence enhancer, and determination of
Avobenzone (AVO), Homosalate, Tinosorb M and Phenyl benzimidazole sulfonic acid
(PBSA) in presence of Octocrylene (OCR) in whitening sunscreen cream, using
micellar medium of Sodium Dodecyl Sulfate (SDS) to enhance fluorescence
intensity. For first product, zero order synchronous spectrofluorimetric method
was used for determination of OMC and AVO, and derivative synchronous
spectrofluorimetric technique was utilized for OT and PBSA in quaternary mixture.
Linear calibration curves were obtained in a concentration range of 0.5-8 MUg mL-
1 for OMC and AVO, and in range of 0.05-3 MUg mL- 1 for OT and 0.001-5 MUg mL- 1
for PBSA, by measuring the fluorescence at 370, 405, 333.2 and 340.6 nm,
respectively. For second product, first derivative synchronous fluorescence
method was used for each UV-filter. A linear calibration curves were obtained in
a concentration range of 0.5-8 MUg mL- 1 for AVO, in range of 0.1-8 MUg mL- 1 for
Homosalate, 2-10 MUg mL- 1 for Tinosorb M and 0.001-5 MUg mL- 1 for PBSA, by
measuring the fluorescence at 409.8, 373, 307.2 and 316.8 nm, respectively. The
detection limits are well below the maximum admissible concentration. The
proposed methods were validated according to ICH guidelines and successfully
applied to determine sunscreens in pure form and in Cosmeceutical formulations.
All the results obtained were compared with those of published methods, where no
significant difference was observed.
PMID- 29344771
TI - Enhancing Capacity for Evidence-Based Policymaking: the Role of Economic
Evaluation Standards.
AB - This commentary will describe some ongoing activities that are moving the federal
government toward stronger use of evidence in decision-making. In particular, the
work of the Commission on Evidence-Based Policymaking points to directions that
have implications for capacity building and the institutionalization of economic
evaluation, as well as mechanisms and resources that could make economic
evaluation more feasible. Bipartisan legislation incorporates many of the
recommendations of the Commission and reinforces efforts already underway at
individual agencies as well as among interagency groups. Understanding the
current context of evidence-based policymaking in the federal government can
enable economic researchers to better influence the processes of capacity
building, shape the designs of evaluations, and inform decision-making. The
commentary highlights areas where further elaboration of economic evaluation
principles could be useful to support evidence building, implementation, and
program improvement.
PMID- 29344772
TI - Safety and efficacy of lamivudine or telbivudine started in early pregnancy for
mothers with active chronic hepatitis B.
AB - BACKGROUND: Few data exist regarding use of nucleos(t)ide analogs started in
early pregnancy for mothers with active chronic hepatitis B (CHB). We assessed
the safety and efficacy of lamivudine/telbivudine initiated in the first
trimester versus no treatment in mothers with active CHB. METHODS: We
retrospectively enrolled 94 mothers newly diagnosed with active CHB in the first
trimester of pregnancy. Patients with or without antiviral therapy were followed
until postpartum week 28. All newborns received immunoprophylaxis. The primary
endpoint was the safety of mothers and infants. The secondary endpoints were
hepatitis B virus (HBV) DNA suppression and mother-to-child transmission (MTCT)
rate. RESULTS: Fifty-nine of the 94 mothers initiated lamivudine/telbivudine
(27/32) in the first trimester of pregnancy; 35 received no treatment. At
delivery, the viral load reduction was similar between lamivudine and
telbivudine. Early initiation of lamivudine/telbivudine significantly increased
the proportion of mothers achieving HBV DNA <106 copies/ml compared with those
with no treatment (100 versus 42.42 %, p < 0.001). At postpartum week 28, the
MTCT rate was significant lower in the treated group than in the control group
(0/61 or 0 versus 4/34 or 11.76 %, p = 0.028). Lamivudine and telbivudine were
well tolerated in the mothers except mild creatine kinase (CK) elevation. There
existed no differences in gestational age, infant length and weight, Apgar score,
adverse events, or birth defect rates between infants from treated and untreated
mothers. CONCLUSIONS: Treatment with lamivudine or telbivudine for active CHB in
early pregnancy appears to be safe and effective for controlling maternal disease
as well as interrupting MTCT.
PMID- 29344773
TI - Beyond Content: Cultural Perspectives on Using the Internet to Deliver a Sexual
Health Intervention to American Indian Youth.
AB - American Indian and Alaska Native (AIAN) youth are characterized by high rates of
pregnancy and risky sexual behavior. Reaching these youth with culturally
appropriate interventions is difficult due to geographic dispersion and cultural
isolation. Online interventions can provide opportunities for reaching and
engaging AIAN youth. However, electronic interventions are also impersonal and
this can be culturally incongruous for AIANs and other populations for whom
traditional ceremonies, practices and patterns of interpersonal communication are
central. This paper describes the application of community based participatory
research methods to: (1) identify concerns about the exclusive use of an online
sexual health program; (2) address community concerns by developing supplemental
class lessons, and (3) evaluate the feasibility and acceptability of the new
hybrid intervention. Data derives from qualitative and quantitative sources.
During the formative phase of the project, qualitative data from partner
interactions was analyzed with participatory inquiry to inform intervention
development. To evaluate the intervention, qualitative data (e.g., interviews,
surveys) were used to understand and explain quantitative measures such as
implementation fidelity and attendance. Implementers were enthusiastic about the
hybrid intervention. The lessons were easy to teach and provided opportunities
for meaningful discussions, adaptations, and community involvement. The use of
online videos was an effective method for providing training. Working with
community partners, we resolved cultural concerns arising from the exclusive use
of the Internet by creating a hybrid intervention. The additional burden for
staff to deliver the class lessons was considered minimal in comparison to the
educational and programmatic benefits of the hybrid intervention.
ClinicalTrials.gov identifier NCT01698073.
PMID- 29344774
TI - Physiological mechanism of osmoregulatory adaptation in anguillid eels.
AB - In recent years, the production of eel larvae has dramatic declines due to
reductions in spawning stocks, overfishing, growth habitat destruction and access
reductions, and pollution. Therefore, it is particularly important and urgent for
artificial production of glass eels. However, the technique of artificial
hatching and rearing larvae is still immature, which has long been regarded as an
extremely difficult task. One of the huge gaps is artificial condition which is
far from the natural condition to develop their capability of osmoregulation.
Thus, understanding their osmoregulatory mechanisms will help to improve the
breed and adapt to the changes in the environment. In this paper, we give a
general review for a study progress of osmoregulatory mechanisms in eels from
five aspects including tissues and organs, ion transporters, hormones, proteins,
and high throughput sequencing methods.
PMID- 29344775
TI - New saliva secretion model based on the expression of Na+-K+ pump and K+ channels
in the apical membrane of parotid acinar cells.
AB - The plasma membrane of parotid acinar cells is functionally divided into apical
and basolateral regions. According to the current model, fluid secretion is
driven by transepithelial ion gradient, which facilitates water movement by
osmosis into the acinar lumen from the interstitium. The osmotic gradient is
created by the apical Cl- efflux and the subsequent paracellular Na+ transport.
In this model, the Na+-K+ pump is located exclusively in the basolateral membrane
and has essential role in salivary secretion, since the driving force for Cl-
transport via basolateral Na+-K+-2Cl- cotransport is generated by the Na+-K+
pump. In addition, the continuous electrochemical gradient for Cl- flow during
acinar cell stimulation is maintained by the basolateral K+ efflux. However,
using a combination of single-cell electrophysiology and Ca2+-imaging, we
demonstrate that photolysis of Ca2+ close to the apical membrane of parotid
acinar cells triggered significant K+ current, indicating that a substantial
amount of K+ is secreted into the lumen during stimulation. Nevertheless, the K+
content of the primary saliva is relatively low, suggesting that K+ might be
reabsorbed through the apical membrane. Therefore, we investigated the
localization of Na+-K+ pumps in acinar cells. We show that the pumps appear
evenly distributed throughout the whole plasma membrane, including the apical
pole of the cell. Based on these results, a new mathematical model of salivary
fluid secretion is presented, where the pump reabsorbs K+ from and secretes Na+
to the lumen, which can partially supplement the paracellular Na+ pathway.
PMID- 29344776
TI - Dawning of a new era in TRP channel structural biology by cryo-electron
microscopy.
AB - Cryo-electron microscopy (cryo-EM) permits the determination of atomic protein
structures by averaging large numbers of individual projection images recorded at
cryogenic temperatures-a method termed single-particle analysis. The cryo
preservation traps proteins within a thin glass-like ice layer, making literally
a freeze image of proteins in solution. Projections of randomly adopted
orientations are merged to reconstruct a 3D density map. While atomic resolution
for highly symmetric viruses was achieved already in 2009, the development of new
sensitive and fast electron detectors has enabled cryo-EM for smaller and
asymmetrical proteins including fragile membrane proteins. As one of the most
important structural biology methods at present, cryo-EM was awarded in October
2017 with the Nobel Prize in Chemistry. The molecular understanding of Transient
Receptor-Potential (TRP) channels has been boosted tremendously by cryo-EM single
particle analysis. Several near-atomic and atomic structures gave important
mechanistic insights, e.g., into ion permeation and selectivity, gating, as well
as into the activation of this enigmatic and medically important membrane protein
family by various chemical and physical stimuli. Lastly, these structures have
set the starting point for the rational design of TRP channel-targeted
therapeutics to counteract life-threatening channelopathies. Here, we attempt a
brief introduction to the method, review the latest advances in cryo-EM structure
determination of TRP channels, and discuss molecular insights into the channel
function based on the wealth of TRP channel cryo-EM structures.
PMID- 29344779
TI - Trigeminal neuropathy in vestibular schwannoma: a treatment algorithm to avoid
long-term morbidity.
AB - BACKGROUND: Trigeminal neuropathy (TGN) can occur as a presenting feature of
vestibular schwannoma (VS) or as an adverse effect of radiosurgery. This study
was designed to evaluate a treatment algorithm for presenting symptoms of TGN in
patients with VS, and a new radiosurgery dosimetric tolerance to avoid TGN after
treatment. Outcome was measured after microsurgery (MS), stereotactic
radiosurgery (SRS), hypofractionated stereotactic radiotherapy (HSRT), and
fractionated radiotherapy (FRT). METHODS: A prospectively held VS database was
retrospectively analysed from 2011 to 2016 at a tertiary university hospital. All
patients who underwent MS from 2011 and all patients who underwent radiotherapy
(SRS, HSRT, FRT) from 2015 were studied. Patients on surveillance and
neurofibromatosis type 2 patients were not included. Patient demographic data,
tumour characteristics, presenting symptoms, and post-treatment outcomes were
analysed. RESULTS: Eighty-eight patients were included in the study (43
microsurgery, 45 radiotherapy). Twenty-seven (31%) patients presented with TGN
symptoms. The median age of patients included was 56.5 (range 6-72 years), with a
median follow-up for MS and SRS of 38 and 20 months, respectively (range 10-80
months). All 27 patients with TGN were offered MS as per protocol. Three patients
declined, or were not fit for surgery, and received FRT. Complete resolution of
TGN symptoms was achieved in all 24 patients who underwent MS and 33% (1/3) of
patients with FRT. Eleven patients experienced transient post-operative
complications (pseudomeningocele (6), meningitis (3), venous sinus thrombosis,
cerebellar haemorrhagic contusion, and posterior fossa haematoma). Of the 45
patients in the radiotherapy cohort, 36 were suitable for SRS, of which 30
patients who met the dose-volume constraints for trigeminal nerve underwent
single-fraction SRS and 6 patients who did not meet the constraints received
HSRT. Nine patients (20%) received FRT including three patients with pre
treatment TGN. None of the patients developed new TGN symptoms following SRS or
HSRT. CONCLUSIONS: Our algorithm to select the optimal treatment modality appears
to achieve comparable or better long-term outcome. Microsurgical resection in our
cohort resulted in complete resolution of symptoms in all patients. None of our
SRS- or HSRT-treated patients developed TGN during the follow-up period. The
adherence to strict trigeminal nerve dose-volume constraints for SRS remains
critical to minimise TGN post treatment. Fractionated radiotherapy is an
alternative for patients who refuse surgery or those who are unfit for surgery.
PMID- 29344780
TI - Intraoperative monitoring of Z-L response (ZLR) and abnormal muscle response
(AMR) during microvascular decompression for hemifacial spasm. Interpreting the
role of ZLR.
AB - BACKGROUND: Z-L response (ZLR) has been suggested to a new electromyographic
(EMG) potential recorded from the facial muscle of patient with hemifacial spasm
(HFS) during microvascular decompression (MVD). Although ZLR has been suggested
to be useful, experience of ZLR monitoring is limited and its significance during
MVD is still unclear. METHODS: To investigate the significance of ZLR, both ZLR
and abnormal muscle response (AMR) were simultaneously recorded before and after
decompression of root exit zone (REZ) in 20 consecutive patients with HFS.
RESULTS: All 19 AMRs elicited before REZ decompression disappeared immediately
after decompression of REZ. ZLRs were also observed before decompression of REZ
in 19 (95%) of 20 patients. Despite negative conversion of AMR after
decompression in 19 patients, ZLR disappeared in only 13 (68.4%) of 19 patients.
Among six sustained ZLRs, three showed reduction in the intensity of ZLRs while
the other three remained unchanged. There were nine cases featuring attachment of
the distal, non-offending portion of offending vessels to the distal course of
the facial nerve in addition to attachment to REZ. Negative ZLR conversion and
presence of peripheral contact of offending vessels to distal facial nerves
showed significant correlations (p < 0.05). ZLR could be elicited by electrical
stimulation at non-REZ-offending portion of the offending arterial wall, attached
to the distal course of the facial nerve. HFS disappeared immediately in all 20
patients. CONCLUSIONS: Although ZLR might be helpful in cases with multiple
offenders, interpretation of ZLR needs caution for non-specific transmission of
electric current through vessel wall to facial nerve.
PMID- 29344777
TI - Giant Cell Arteritis: Practical Pearls and Updates.
AB - PURPOSE OF REVIEW: The purpose of this review is to summarize recent updates and
distill practical points from the literature which can be applied to the care of
patients with suspected and confirmed giant cell arteritis (GCA). RECENT
FINDINGS: Contemporary thinking implicates a fundamental failure of T regulatory
cell function in GCA pathophysiology, representing opportunity for novel
therapeutic avenues. Tocilizumab has become the first Food and Drug
Administration-approved treatment for GCA following demonstration of efficacy and
safety in a phase 3 clinical trial. There have been significant parallel advances
in both our understanding of GCA pathophysiology and treatment. Tocilizumab, and
other agents currently under investigation in phase 2 and 3 clinical trials,
presents a new horizon of hope for both disease remission and avoidance of
glucocorticoid-related complications.
PMID- 29344778
TI - The Relationship Between Vancomycin Trough Concentrations and AUC/MIC Ratios in
Pediatric Patients: A Qualitative Systematic Review.
AB - BACKGROUND: In adults, the area under the concentration-time curve (AUC) divided
by the minimum inhibitory concentration (MIC) is associated with better clinical
and bacteriological response to vancomycin in patients with methicillin-resistant
Staphylococcus aureus who achieve target AUC/MIC >= 400. This target is often
extrapolated to pediatric patients despite the lack of similar evidence. The
impracticalities of calculating the AUC in practice means vancomycin trough
concentrations are used to predict the AUC/MIC. OBJECTIVE: This review aimed to
determine the relationship between vancomycin trough concentrations and AUC/MIC
in pediatric patients. METHODS: We searched the MEDLINE and Embase databases, the
Cochrane Database of Systematic Reviews, and the Cochrane Central Register of
Controlled Trials using the medical subject heading (MeSH) terms vancomycin and
AUC and pediatric* or paediatric*. Articles were included if they were published
in English and reported a relationship between vancomycin trough concentrations
and AUC/MIC. RESULTS: Of 122 articles retrieved, 11 met the inclusion criteria.
One trial reported a relationship between vancomycin trough concentrations,
AUC/MIC, and clinical outcomes but was likely underpowered. Five studies found
troughs 6-10 mg/l were sufficient to attain an AUC/MIC > 400 in most general
hospitalized pediatric patients. One study in patients undergoing cardiothoracic
surgery found a trough of 18.4 mg/l achieved an AUC/MIC > 400. Two oncology
studies reported troughs >= 15 mg/l likely attained an AUC/MIC >= 400. In
critical care patients: one study found a trough of 9 mg/l did not attain the
AUC/MIC target; another found 7 mg/l corresponded to an AUC/MIC of 400.
CONCLUSIONS: Potential vancomycin targets varied based on the population studied
but, for general hospitalized pediatric patients, troughs of 6-10 mg/l are likely
sufficient to achieve AUC/MIC >= 400. For MIC >= 2 mg/l, higher troughs are
likely necessary to achieve an AUC/MIC >= 400. More research is needed to
determine the relationships between vancomycin trough concentrations, AUC/MIC,
and clinical outcomes.
PMID- 29344781
TI - Automated 3D Soma Segmentation with Morphological Surface Evolution for Neuron
Reconstruction.
AB - The automatic neuron reconstruction is important since it accelerates the
collection of 3D neuron models for the neuronal morphological studies. The
majority of the previous neuron reconstruction methods only focused on tracing
neuron fibres without considering the somatic surface. Thus, topological errors
often present around the soma area in the results obtained by these tracing
methods. Segmentation of the soma structures can be embedded in the existing
neuron tracing methods to reduce such topological errors. In this paper, we
present a novel method to segment the soma structures with complex geometry. It
can be applied along with the existing methods in a fully automated pipeline. An
approximate bounding block is firstly estimated based on a geodesic distance
transform. Then the soma segmentation is obtained by evolving the surface with a
set of morphological operators inside the initial bounding region. By evaluating
the methods against the challenging images released by the BigNeuron project, we
showed that the proposed method can outperform the existing soma segmentation
methods regarding the accuracy. We also showed that the soma segmentation can be
used for enhancing the results of existing neuron tracing methods.
PMID- 29344782
TI - Accuracy and efficiency of published film dosimetry techniques using a flat-bed
scanner and EBT3 film.
AB - Gafchromic EBT3 film is widely used for patient specific quality assurance of
complex treatment plans. Film dosimetry techniques commonly involve the use of
transmission scanning to produce TIFF files, which are analysed using a non
linear calibration relationship between the dose and red channel net optical
density (netOD). Numerous film calibration techniques featured in the literature
have not been independently verified or evaluated. A range of previously
published film dosimetry techniques were re-evaluated, to identify whether these
methods produce better results than the commonly-used non-linear, netOD method.
EBT3 film was irradiated at calibration doses between 0 and 4000 cGy and 25
pieces of film were irradiated at 200 cGy to evaluate uniformity. The film was
scanned using two different scanners: The Epson Perfection V800 and the Epson
Expression 10000XL. Calibration curves, uncertainty in the fit of the curve,
overall uncertainty and uniformity were calculated following the methods
described by the different calibration techniques. It was found that protocols
based on a conventional film dosimetry technique produced results that were
accurate and uniform to within 1%, while some of the unconventional techniques
produced much higher uncertainties (> 25% for some techniques). Some of the
uncommon methods produced reliable results when irradiated to the standard
treatment doses (< 400 cGy), however none could be recommended as an efficient or
accurate replacement for a common film analysis technique which uses transmission
scanning, red colour channel analysis, netOD and a non-linear calibration curve
for measuring doses up to 4000 cGy when using EBT3 film.
PMID- 29344784
TI - The feasibility and efficacy of pure laparoscopic repeat hepatectomy.
AB - BACKGROUND: Repeat hepatectomy is often required for hepatocellular carcinoma and
metastatic tumors. However, this procedure is technically challenging, so
laparoscopic repeat hepatectomy (LRH) has not been widely adopted. The aim of
this study was to evaluate the feasibility and efficacy of LRH compared with open
repeat hepatectomy (ORH) and laparoscopic primary hepatectomy (LPH). METHODS: We
introduced laparoscopic hepatectomy at our institution in April 2014. We
performed 127 LPH (LPH group) and 33 LRH procedures (LRH group) from April 2014
to April 2017; 37 patients underwent ORH from January 2010 to April 2017 (ORH
group). This study retrospectively compared the patient characteristics and short
term outcomes of the LRH and ORH groups as well as the LRH and LPH groups.
RESULTS: There were no conversions to open surgery in the LRH group. In comparing
the LRH and ORH groups, there were no significant differences in patient
characteristics except for the type of approach to the previous hepatectomy (p =
0.004) and indocyanine green retention rate at 15 min (median 12.5 vs. 8.75%, p =
0.026). The LRH group had less blood loss (median 30 mL vs. 652 mL; p < 0.001),
less intraoperative transfusion (6.1 vs. 32.4%; p = 0.006), and shorter
postoperative hospital stays (median 6.5 days vs. 9.0 days; p < 0.001). There
were no differences with regard to operation time, severe postoperative
complications, and mortality. In comparing the LRH and LPH groups, there was a
significant difference only in past history of abdominal surgery (100 vs. 61.4%;
p < 0.001). In the short-term outcomes, the postoperative hospital stay was
significantly shorter in the LRH group (median 6.5 days vs. 7 days; p = 0.033),
and the other results were comparable between the two groups. CONCLUSIONS: LRH is
feasible and useful for repeat hepatectomy, achieving good short-term outcomes.
PMID- 29344783
TI - Endoscopic treatment of walled-off pancreatic necrosis complicated with
pancreaticocolonic fistula.
AB - BACKGROUND: Pancreaticocolonic fistulas (PCFs) are serious complication of acute
pancreatitis related with high mortality. The aim of this study was to evaluate
the efficiency and safety of endoscopic treatment in patients with walled-off
pancreatic necrosis (WOPN) complicated with PCF. METHODS: This is a retrospective
analysis of results and complications in the group of 226 patients, who underwent
endoscopic treatment of symptomatic WOPN between years 2001 and 2016 in the
Department of Gastroenterology and Hepatology of Medical University of Gdansk.
RESULTS: PCF was recognized in 21/226 (9.29%) patients. Transmural drainage was
performed in 20/21 (95.24%) patients. Transpapillary drainage was used in 2/21
(9.52) patients. The mean time since the start of endotherapy to the diagnosis of
a fistulas was 9 (3-21) days. Fluoroscopic nasocystic tube-check imaging of an
existing drain was the initial imaging diagnosis of a PCF in 19/21 (90.48%)
patients. The mean duration of endoscopic drainage of WOPN was 39.29 (15-87)
days. Procedure-related adverse events occurred in 10/21 (47.62%) patients and
most of them were treated conservatively. Three patients required surgical
treatment. One patient died during endotherapy. The closure of PCF was confirmed
via imaging in 17/21 (80.95%) patients. The average time since the recognition
till the closure of PCF was 21 (14-48) days. Complete therapeutic success of WOPN
complicated with PCF was reached in 16/21 (76.19%) patients. Long-term success of
endoscopic treatment was achieved in 15/21 (71.43%) patients. CONCLUSIONS:
Endoscopic treatment of patients with WOPN complicated with PCF is an effective
method with an acceptable number of complications. The complete regression of the
WOPN may lead to spontaneous closure of pancreaticocolonic fistulas.
PMID- 29344785
TI - Laparoscopic intracorporeal rectus aponeuroplasty (LIRA technique): a step
forward in minimally invasive abdominal wall reconstruction for ventral hernia
repair (LVHR).
AB - BACKGROUND: Closing the defect (CD) during laparoscopic ventral hernia repair
began to be performed in order to decrease seroma, to improve the functionality
of the abdominal wall, and to decrease the bulging effect. However, tension at
the incision after CD in large defects is related to an increased rate of pain
and recurrence. We present the preliminary results of a new technique for medium
midline hernias as an alternative to conventional CD. METHODS: A prospective
controlled study was conducted from January 2015 to January 2017 to evaluate an
elective new procedure (LIRA) performed on patients with midline ventral hernias
(4-10 cm width). The posterior rectus aponeurosis was opened lengthwise around
the hernia defect using a laparoscopic approach to create two flaps and was then
sutured. The size of the flaps was estimated using a mathematical formula. An on
lay mesh was placed intraperitoneal overlapping the fascia defect. The data
analyzed included patient demographics, operative parameters, and complications.
A computerized tomography was performed preoperatively and postoperatively (1
month and 1 year) to evaluate recurrence, distance between rectus and seroma.
RESULTS: Twelve patients were included. Mean width of the defect was 5.5 cm.
Average VAS (24 h) was 3.9, 1.1 (1 month), and 0 (1 year). Mean preoperative
distance between rectus was 5.5 cm; postoperative was 2.2 cm (1 year).
Radiological seroma at first month was detected in 50%. Mean follow-up was 15
months. CONCLUSION: The LIRA technique could be considered as an alternative to
conventional CD or endoscopic component separation for medium defects under 10 cm
in width. This technique obtained a "no tension" effect that could be related to
a lower rate of postoperative pain with no recurrence or bulging, being a safe,
feasible, and reproducible technique.
PMID- 29344786
TI - Colonoscopy-induced acute diverticulitis: myth or reality?
AB - BACKGROUND: Colonoscopy in patients with diverticulosis can be technically
challenging and limited data exist relating to the risk of post-colonoscopy
diverticulitis. Our aim was to evaluate the incidence, management, and outcomes
of acute diverticulitis following colonoscopy. METHODS: Study design is
retrospective cohort study. Data were gathered by conducting an automated search
of the electronic patient database using current procedural terminology and ICD-9
codes. Patients who underwent a colonoscopy from 2003 to 2012 were reviewed to
find patients who developed acute diverticulitis within 30 days after
colonoscopy. Patient demographics and colonoscopy-related outcomes were
documented, which include interval between colonoscopy and diverticulitis,
colonoscopy indication, simultaneous colonoscopic interventions, and follow-up
after colonoscopy. RESULTS: From 236,377 colonoscopies performed during the study
period, 68 patients (mean age 56 years) developed post-colonoscopy diverticulitis
(0.029%; 2.9 per 10,000 colonoscopies). Incomplete colonoscopies were more
frequent among patients with a history of previous diverticulitis [n = 10 (29%)
vs. n = 3 (9%), p = 0.03]. Mean time to develop diverticulitis after colonoscopy
was 12 +/- 8 days, and 30 (44%) patients required hospitalization. 34 (50%)
patients had a history of diverticulitis prior to colonoscopy. Among those
patients, 14 underwent colonoscopy with an indication of surveillance for
previous disease. When colonoscopy was performed within 6 weeks of a
diverticulitis attack, surgical intervention was required more often when
compared with colonoscopies performed after 6 weeks of an acute attack [n = 6
(100%) vs. n = 10 (36%), p = 0.006]. 6 (9%) out of 68 patients received emergency
surgical treatment. 15 (24%) out of 62 patients who had non-surgical treatment
initially underwent an elective sigmoidectomy at a later date. Recurrent
diverticulitis developed in 16 (23%) patients after post-colonoscopy
diverticulitis. CONCLUSIONS: Post-colonoscopy diverticulitis is a rare, but
potentially serious complication. Although a rare entity, possibility of this
complication should be kept in mind in patients presenting with symptoms after
colonoscopy.
PMID- 29344787
TI - A novel fully covered double-bump stent for staple line leaks after bariatric
surgery: a retrospective analysis.
AB - BACKGROUND: Staple line leakage after bariatric surgery can be treated by
endoscopic placement of a self-expandable stent. The success rate of stent
placement is generally high, but migration is a frequent adverse event that
hampers successful treatment. The Niti-S Beta stent is a fully covered double
bump stent that was specifically designed to prevent migration. This study aimed
to evaluate the effectiveness and adverse event rate of the Niti-S Beta stent.
METHODS: A retrospective study was performed in three high-volume bariatric
centers. All consecutive patients between 2009 and 2016 who underwent placement
of a Beta stent for staple line leakage were included. Primary outcome was
resolution of the leakage; secondary outcome was the adverse event rate including
migration. RESULTS: Thirty-eight patients were included. Twenty-five (66%) had
resolution of the leakage. Success rate was higher in patients who were treated
with implantation of a Beta stent as initial treatment (100%) than in patients
who were treated with a stent after revisional surgery had failed (55%, p =
0.013). Migration occurred in 12 patients (32%). There were two severe adverse
events requiring surgical intervention, including a bleeding from an aorto
esophageal fistula. CONCLUSIONS: The success rate and the migration rate of the
Beta stent seem comparable to other stents in this retrospective study. Despite
the novel double-bump structure of the stent, the migration rate does not seem to
be decreased.
PMID- 29344788
TI - Intracorporeal versus extracorporeal anastomosis after laparoscopic left
colectomy for splenic flexure cancer: results from a multi-institutional audit on
181 consecutive patients.
AB - Although intracorporeal anastomosis has been demonstrated to be safe and
effective after right colectomy, limited data are available about its efficacy
after left colectomy for colon cancer located in splenic flexure. A multi
institutional audit was designed, including 92 patients who underwent
laparoscopic left colectomy with intracorporeal anastomosis (IA) compared with 89
matched patients who underwent a laparoscopic left colectomy with extracorporeal
anastomosis (EA). There was no significant difference in terms of age, sex, BMI,
and ASA score between the two groups. Post-surgical history and stage of disease
according to AJCC/UICC TNM were also similar. IA and EA groups demonstrated
similar oncologic radicality in terms of the number of lymph nodes harvested
(18.5 +/- 9 vs. 17.5 +/- 8.4; p = 0.48). Recovery after surgery was also better
in patients who underwent IA, as confirmed by the shorter time to flatus in the
IA group (2.6 +/- 1.1 days vs. 3.4 +/- 1.2 days; p < 0.001) and higher post
operative pain expressed in the mean VAS Scale in the EA group (1.7 +/- 2.1 vs.
3.5 +/- 1.6; p < 0.001). Laparoscopic left colectomy with intracorporeal
anastomosis was associated with a lower rate of post-operative complications (OR
6.7, 95% CI 2.2-20; p = 0.001). However, when stratifying according to Clavien
classification, the difference was consistently confirmed for less severe (class
I and II) complications (OR 7.6, 95% CI 2.5-23, p = 0.001) but not for class III,
IV, and V complications (OR 1.8, 95% CI 0.1-16.9; p = 0.59). Our results were
consistent to hypothesize that a complete laparoscopic approach could be
considered a safe method to perform laparoscopic left colectomy with the
advantage of a guaranteed faster recovery after surgery. Further randomized
clinical trials are needed to obtain a more definitive conclusion.
PMID- 29344789
TI - Laparoscopic conversion in colorectal cancer surgery; is there any improvement
over time at a population level?
AB - Conversion of laparoscopic colorectal cancer resection has been associated with
worse outcome, but this might have been related to a learning curve effect. This
study aimed to evaluate incidence, predictive factors and outcomes of
laparoscopic conversion after the implementation phase of laparoscopic surgery at
a population level. Patients undergoing elective resection of non-locally
advanced, non-metastatic colorectal cancer between 2011 and 2015 were included.
Data were extracted from the Dutch Surgical Colorectal Audit. Patients were
grouped as laparoscopic completed (LR), laparoscopic converted (CONV) with
further specification of timing (within or after 30 min) as registered in the
DSCA, and open resection (OR). Uni- and multi-variate analyses were used to
determine predictors of conversion and outcome (complicated course and
mortality), with evaluation of trends over time. A total of 23,044 patients with
colon cancer and 11,324 with rectal cancer were included. Between 2011 and 2015,
use of laparoscopy increased from 55 to 84% in colon cancer, and from 49 to 89%
in rectal cancer. Conversion rates decreased from 11.8 to 8.6% and from 13 to
8.0%, respectively. Laparoscopic hospital volume was independently associated
with conversion rate. Only for colon cancer, the rate of complicated course was
significantly higher after CONV compared to OR (adjusted odds ratio 1.486; 95% CI
1.298-1.702), and significantly higher after late (> 30 min) compared to early
conversion (adjusted odds ratio 1.341; 1.046-1.719). There was no impact of CONV
on mortality in both colon and rectal cancer. The use of laparoscopic colorectal
cancer surgery increased to more than 80% at a national level, accompanied by a
decrease in conversion which is significantly related to the laparoscopic
hospital volume. Conversion was only associated with complicated course in colon
cancer, especially when the reason for conversion consisted of an intra-operative
complication, without affecting mortality.
PMID- 29344790
TI - Prospective analysis of delayed colorectal post-polypectomy bleeding.
AB - BACKGROUNDS/AIMS: Although post-polypectomy bleeding is the most frequent
complication after colonoscopic polypectomy, only few studies have investigated
the incidence of bleeding prospectively. The aim of this study was to investigate
the incidence of delayed post-polypectomy bleeding and its associated risk
factors prospectively. METHODS: Patients who underwent colonoscopic polypectomy
at Kangbuk Samsung Hospital from January 2013 to December 2014 were prospectively
enrolled in this study. Trained nurses contacted patients via telephone 7 and 30
days after polypectomy and completed a standardized questionnaire regarding the
development of bleeding. Delayed post-polypectomy bleeding was categorized as
minor or major and early or late bleeding. Major delayed bleeding was defined as
a > 2-g/dL drop in the hemoglobin level, requiring hospitalization for control of
bleeding or blood transfusion; late delayed bleeding was defined as bleeding
occurring later than 24 h after polypectomy. RESULTS: A total of 8175
colonoscopic polypectomies were performed in 3887 patients. Overall, 133 (3.4%)
patients developed delayed post-polypectomy bleeding. Among them, 90 (2.3%) and
43 (1.1%) patients developed minor and major delayed bleeding, respectively, and
39 (1.0%) patients developed late delayed bleeding. In the polyp-based
multivariate analysis, young age (< 50 years; odds ratio [OR] 2.10; 95%
confidence interval [CI] 1.18-3.68), aspirin use (OR 2.78; 95% CI 1.23-6.31), and
polyp size of > 10 mm (OR 2.45; 95% CI 1.38-4.36) were significant risk factors
for major delayed bleeding, while young age (< 50 years; OR 2.6; 95% CI 1.35
5.12) and immediate bleeding (OR 3.3; 95% CI 1.49-7.30) were significant risk
factors for late delayed bleeding. CONCLUSIONS: Young age, aspirin use, polyp
size, and immediate bleeding were found to be independent risk factors for
delayed post-polypectomy bleeding.
PMID- 29344791
TI - SAGES's advanced GI/MIS fellowship curriculum pilot project.
AB - BACKGROUND: The American health care system faces deficits in quality and
quantity of surgeons. SAGES is a major stakeholder in surgical fellowship
training and is responsible for defining the curriculum for the Advanced GI/MIS
fellowship. SAGES leadership is actively adapting this curriculum. METHODS: The
process of reform began in 2014 through a series of iterative meetings and
discussions. A working group within the Resident and Fellow Training Committee
reviewed case log data from 2012 to 2015. These data were used to propose new
criteria designed to provide adequate exposure to core content. The working group
also proposed using video assessment of an MIS case to provide objective
assessment of competency. RESULTS: Case log data were available for 326 fellows
with a total of 85,154 cases logged (median 227 per fellow). The working group
proposed new criteria starting with minimum case volumes for five defined
categories including foregut (20), bariatrics (25), inguinal hernia (10), ventral
hernia (10), and solid organ/colon/thoracic (10). Fellows are expected to perform
an additional 75 complex MIS cases of any category for a total of 150 required
cases overall. The proposal also included a minimum volume of flexible endoscopy
(50) and submission of an MIS foregut case for video assessment. The new criteria
more clearly defined which surgeon roles count for major credit within individual
categories. Fourteen fellowships volunteered to pilot these new criteria for the
2017-2018 academic year. CONCLUSIONS: The new SAGES Advanced GI/MIS fellowship
has been crafted to better define the core content that should be contained in
these fellowships, while still allowing sufficient heterogeneity so that
individual learners can tailor their training to specific areas of interest. The
criteria also introduce innovative, evidence-based methods for assessing
competency. Pending the results of the pilot program, SAGES will consider broad
implementation of the new fellowship criteria.
PMID- 29344792
TI - Post-conditioning hormesis creates a "subtraction to background" disease process:
biological, aging, and environmental risk assessment implications.
AB - The interaction of background disease processes with environmental induced
diseases has long been an issue of considerable interest and debate with respect
to its impact on risk assessment. Whether and to what extent these processes
should be considered independent or additive to background has been the principal
focus of debate. The concept of hormesis, a biphasic dose response characterized
by a low dose stimulation and a high dose inhibition, as framed within the
context of post-conditioning, reveal the occurrence of a third type of
"background" possibility, that of "subtraction to background". This novel
application of the hormesis concept, which is framed within the biological
context of post-conditioning adaptive processes, offers considerable implications
for the assessment of aging and environmental risk assessment.
PMID- 29344793
TI - The Role of Bone Secreted Factors in Burn-Induced Muscle Cachexia.
AB - PURPOSE OF REVIEW: Burn injury results in resorptive bone loss, failure to make
new bone, and muscle protein breakdown resulting in cachexia. The purpose of this
review is to examine the relationship between bone loss and muscle atrophy in
burn injury with a view to understanding the process at work and how it may apply
to other conditions that have similar features. RECENT FINDINGS: We present data
suggesting that the use of bisphosphonates in the first 10 days following the
burn prevents not only the resorptive bone loss but also the muscle wasting.
While an extra-osseous effect of bisphosphonates remains possible, existing
evidence points to a paracrine effect of bone on maintenance of muscle mass and
strength. Proposed paracrine factors produced by bone include prostaglandin E2
and components of the Wnt signaling pathway. TGFbeta may be a bone paracrine
factor that causes oxidative damage to muscle. In the light of the pattern of
evidence, burn patients suffer acute resorptive bone loss and muscle wasting.
This is likely due to the effects of inflammatory cytokines and endogenous
glucocorticoid production in exacerbating oxidative stress. Early use of
bisphosphonates can maintain bone mass leading to a paracrine effect of bone in
the maintenance of muscle mass, although one cannot completely discount a direct
effect of bisphosphonate on muscle. Because investigators report this
relationship in a variety of conditions in addition to burns, physicians should
seriously consider the early use of bisphosphonates to maintain bone and muscle
mass in a variety of neuromuscular and skeletal diseases.
PMID- 29344794
TI - Ticagrelor for Secondary Prevention of Atherothrombotic Events After Myocardial
Infarction: An Evidence Review Group Perspective of a NICE Single Technology
Appraisal.
AB - The National Institute for Health and Care Excellence (NICE) invited AstraZeneca,
the manufacturer of ticagrelor (Brilique(r)), to submit evidence on the clinical
and cost effectiveness of ticagrelor 60 mg twice daily (BID) in combination with
low-dose aspirin [acetylsalicylic acid (ASA)] compared with ASA only for
secondary prevention of atherothrombotic events in patients with a history of
myocardial infarction (MI) and who are at increased risk of atherothrombotic
events. Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Maastricht
University Medical Centre+, was commissioned as the evidence review group (ERG).
This paper summarises the company submission (CS), the ERG report and the NICE
guidance produced by the appraisal committee (AC) for the use of ticagrelor in
England and Wales. The ERG critically reviewed the clinical- and cost
effectiveness evidence in the CS. The systematic review conducted as part of the
CS identified one randomised controlled trial (RCT), PEGASUS-TIMI 54. This trial
reported the time to first occurrence of any event from the composite of
cardiovascular death, MI and stroke as the primary outcome (hazard ratio 0.84
ticagrelor 60 mg BID vs. placebo, 95% confidence interval 0.74-0.95). The
population addressed in the CS was a subgroup of the PEGASUS-TIMI 54 trial
population, i.e. the 'base-case' population, which comprised patients who had
experienced an MI between 1 and 2 years ago, whereas the full trial population
included patients who had experienced an MI between 1 and 3 years ago. While the
ERG believed the findings of this RCT to be robust, doubts concerning the
applicability of the trial to UK patients were raised. The company submitted an
individual patient simulation model to estimate the cost-effectiveness of
ticagrelor 60 mg BID + ASA versus ASA only. Parametric time-to-event models were
used to estimate the time to first and subsequent (cardiovascular) events, time
to treatment discontinuation and time to adverse events. The company's base-case
analysis resulted in an incremental cost-effectiveness ratio (ICER) of L20,098
per quality-adjusted life-year (QALY) gained. The main issues surrounding the
cost effectiveness of ticagrelor 60 mg BID + ASA were the use of parametric time
to-event models estimated based on the full trial population instead of being
fitted to the 'label' population (the 'label' population comprised the 'base
case' population and patients who started ticagrelor 60 mg BID within 1 year of
previous adenosine diphosphate inhibitor treatment), the incorrect implementation
of the probabilistic sensitivity analysis (PSA) of the individual patient
simulation, and simplifications of the model structure that may have biased the
health benefits and costs estimations of the intervention and comparator. The ERG
believed the use of the full trial population to inform the parametric time-to
event models was not appropriate because the 'label' population was the main
focus of the scope and CS. The ERG could not investigate the magnitude of the
bias introduced by this assumption. The PSA of the individual patient simulation
provided unreliable probabilistic results and underestimated the uncertainty
surrounding the results because it was based on a single patient. The ERG used
the cohort simulation presented in the cost-effectiveness model to perform its
base-case and additional analyses and to obtain probabilistic results. The ERG
amended the company cost-effectiveness model, which resulted in an ERG base-case
ICER of L24,711 per QALY gained. In its final guidance, the AC recommended
treatment with ticagrelor 60 mg BID + low-dose ASA for secondary prevention of
atherothrombotic events in adults who have had an MI and are at increased risk of
atherothrombotic events.
PMID- 29344797
TI - Annular dynamics of memo3D annuloplasty ring evaluated by 3D transesophageal
echocardiography.
AB - BACKGROUND: We assessed the mitral annular motion after mitral valve repair with
the Sorin Memo 3D(r) (Sorin Group Italia S.r.L., Saluggia, Italy), which is a
unique complete semirigid annuloplasty ring intended to restore the systolic
profile of the mitral annulus while adapting to the physiologic dynamism of the
annulus, using transesophageal real-time three-dimensional echocardiography.
METHODS: 17 patients (12 male; mean age 60.4 +/- 14.9 years) who underwent mitral
annuloplasty using the Memo 3D ring were investigated. Mitral annular motion was
assessed using QLAB(r)version8 allowing for a full evaluation of the mitral
annulus dynamics. The mitral annular dimensions were measured throughout the
cardiac cycle using 4D MV assessment2(r) while saddle shape was assessed through
sequential measurements by RealView(r). RESULTS: Saddle shape configuration of
the mitral annulus and posterior and anterior leaflet motion could be observed
during systole and diastole. The mitral annular area changed during the cardiac
cycle by 5.7 +/- 1.8%.The circumference length and diameter also changed
throughout the cardiac cycle. The annular height was significantly higher in mid
systole than in mid-diastole (p < 0.05). CONCLUSIONS: The Memo 3D ring maintained
a physiological saddle-shape configuration throughout the cardiac cycle. Real
time three-dimensional echocardiography analysis confirmed the motion and
flexibility of the Memo 3D ring upon implantation.
PMID- 29344798
TI - Association between values of preoperative 6-min walk test and surgical outcomes
in lung cancer patients with decreased predicted postoperative pulmonary
function.
AB - OBJECTIVE: We retrospectively investigated the possibility that the 6-min walk
test (6MWT) could predict surgical outcomes in lung cancer patients with
decreased predicted postoperative (ppo) lung function. METHODS: Patients were
enrolled based on their preoperative spirometry: <60% of the ppo forced
expiratory volume in 1 s (FEV1.0) or < 60% of the ppo lung carbon monoxide
diffusion capacity (DLco). Morbidity, oxygen inhalation required > 10 days, home
oxygen therapy (HOT) requirement, unexpected readmission within 90 days, and 90
day mortality were included as surgical outcomes. The correlations with walking
distance and the minimum SpO2 (SpO2min) and maximum decrease in SpO2 (DeltaSpO2)
during the 6MWT were analyzed using logistic regression analysis, adjusting for
age, sex, and surgical procedure. RESULTS: Altogether, 121 patients were
analyzed. Logistic regression analysis revealed that higher DeltaSpO2 and lower
SpO2min were significantly correlated with a higher risk of prolonged need for
oxygen inhalation and HOT, surgical morbidity, and 90-day mortality. Cut-off
values of > 4% for DeltaSpO2 were significant for prolonged oxygen inhalation and
surgical morbidity. Cut-off values of < 89-91% for SpO2min were also significant
for the need for prolonged oxygen inhalation, surgical morbidity, and HOT
requirement. There were no significant correlations between walking distance and
each surgical outcome. CONCLUSIONS: Oxygen desaturation during 6MWT was a good
predictor for poor surgical outcomes in lung cancer patients with decreased ppo
pulmonary function.
PMID- 29344799
TI - Correction to: Current status of cardiovascular surgery in Japan, 2013 and 2014:
A report based on the Japan Cardiovascular Surgery database 3. Coronary artery
bypass surgery.
AB - In the original publication of this article, Table 4 was published incorrectly.
The correct Table 4 is given in the following page.
PMID- 29344800
TI - Platycodon saponins from Platycodi Radix (Platycodon grandiflorum) for the Green
Synthesis of Gold and Silver Nanoparticles.
AB - A green synthesis of gold and silver nanoparticles is described in the present
report using platycodon saponins from Platycodi Radix (Platycodon grandiflorum)
as reducing agents. Platycodin D (PD), a major triterpenoidal platycodon saponin,
was enriched by an enzymatic transformation of an aqueous extract of Platycodi
Radix. This PD-enriched fraction was utilized for processing reduction reactions
of gold and silver salts to synthesize gold nanoparticles (PD-AuNPs) and silver
nanoparticles (PD-AgNPs), respectively. No other chemicals were introduced during
the reduction reactions, providing an entirely green, eco-friendly, and
sustainable method. UV-visible spectra showed the surface plasmon resonance bands
of PD-AuNPs at 536 nm and PD-AgNPs at 427 nm. Spherically shaped nanoparticles
were observed from high-resolution transmission electron microscopy with average
diameters of 14.94 +/- 2.14 nm for PD-AuNPs and 18.40 +/- 3.20 nm for PD-AgNPs.
Minor triangular and other polygonal shapes were also observed for PD-AuNPs along
with spherical ones. Atomic force microscopy (AFM) images also demonstrated that
both nanoparticles were mostly spherical in shape. Curvature-dependent evolution
was employed to enhance the AFM images and precisely measure the sizes of the
nanoparticles. The sizes were measured as 19.14 nm for PD-AuNPs and 29.93 nm for
PD-AgNPs from the enhanced AFM images. Face-centered cubic structures for both
nanoparticles were confirmed by strong diffraction patterns from high-resolution
X-ray diffraction analyses. Fourier transform infrared spectra revealed the
contribution of -OH, aromatic C=C, C-O, and C-H functional groups to the
synthesis. Furthermore, the catalytic activity of PD-AuNPs was assessed with a
reduction reaction of 4-nitrophenol to 4-aminophenol in the presence of sodium
borohydride. The catalytic activity results suggest the potential application of
these gold nanoparticles as catalysts in the future. The green strategy reported
in this study using saponins as reducing agents will pave new roads to develop
novel nanomaterials with versatile applications.
PMID- 29344801
TI - Toxoplasma gondii in sympatric domestic and wild ungulates in the Mediterranean
ecosystem.
AB - Toxoplasma gondii is a zoonotic protozoan of worldwide distribution. The present
study provides information on risk factors affecting T. gondii infection in
domestic and free-ranging wild ungulates sharing habitats in Mediterranean
ecosystems in Spain. Serum samples from 482 extensively reared domestic ruminants
and 2351 wild ungulates were tested for T. gondii antibodies using the modified
agglutination test (MAT, cut-off 1:25). Toxoplasma gondii seroprevalence was
41.2% of 194 sheep, 18.6% of 199 cattle and 5.6% of 89 goats. The main risk
factors associated with infection in livestock were the presence of cats, feeding
on the ground and at stubble fields. In wild ungulates, T. gondii antibodies were
detected in 10.5% of 1063 red deer, 15.6% of 294 fallow deer, 5.6% of 216
European mouflon, 5.6% of 90 Spanish ibex, 13.6% of 22 roe deer and 18.6% of 666
wild boars. The risk factors affecting T. gondii infection in wildlife were
species, age and hunting season. Significantly higher seroprevalence was found in
domestic ruminants, particularly in sheep, compared to the wild species tested.
The present study indicates widespread exposure to T. gondii among domestic and
wild ungulates in Southern Spain, with significant differences among species
sharing the same ecosystem. The high seroprevalence observed in domestic
ruminants, particularly in sheep, reinforces the need for farm management
practices to control the risk factors associated with T. gondii infection in
extensively reared livestock. Consumption of raw and undercooked food products
from domestic and wildlife species may have important implications for public
health.
PMID- 29344802
TI - Protein profiling of Acanthamoeba species using MALDI-TOF MS for specific
identification of Acanthamoeba genotype.
AB - Acanthamoeba spp. are ubiquitous in the environment and have the potential to
cause severe infections. The different genotypes of Acanthamoeba have been shown
to influence the severity of the disease and response to therapy. Characterizing
Acanthamoeba spp. upto genotype can aid in infection control practices. Twenty
five Acanthamoeba isolates, characterized by 18S rDNA sequencing, were subjected
to MALDI-TOF MS analysis by creating a database for the individual genotypes. The
differentiating features of the various spectra were observed; the coded samples
were then tested against the created database. The results of identification were
compared with sequencing. Five different genotypes were obtained-T3, T4, T5, T10,
and T11. Spectral analysis revealed genus-specific and genotype-specific peaks.
The peak patterns for individual genotype were discrete and reproducible.
Clinical isolates produced different peaks from the environmental isolate of the
same genotype. A concordance of 92% was obtained with MALDI-TOF MS in comparison
with 18sDNA sequencing. MALDI-TOF MS, once optimized, has the potential to
reliably identify the genotype of Acanthamoeba spp. and to differentiate clinical
isolate from mere contaminant.
PMID- 29344803
TI - Toxoplasma gondii: prevalence and characterization of new genotypes in free-range
chickens from south Brazil.
AB - Toxoplasma gondii is an intracellular parasite that can infect all warm-blooded
animals including humans. Recent studies showed that T. gondii strains from South
America are genetically diverse. The present work aimed to determine T. gondii
prevalence in free-ranging chicken in northwest Parana state in Brazil by two
serological tests, to isolate the parasites from seropositive chickens and to
genotype the isolates. Antibodies to T. gondii in 386 serum samples from 24 farms
were investigated by immunofluorescence antibody assay (IFA) and modified
agglutination test (MAT). Samples having titers >= 16 were considered positive
for both tests. Among the 386 serum samples, 102 (26.4%) were positive for IFA,
64 (16.6%) were positive for MAT, 47 (12.2%) were positive in both tests, and 119
(30.8%) were positive in at least one of the two tests. Brain and pool of heart,
lung, and liver from the 119 seropositive chickens were used for mouse bioassay
to isolate the parasites. Thirty eight (31.9%) of these seropositive chickens
were considered positives in mouse bioassay and 18 isolates were obtained. The
isolates were characterized by 10 PCR-RFLP genetic markers including SAG1, SAG2
(5'-3'SAG2, alt.SAG2), SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico.
Results of genotyping were compared with the genotypes in ToxoDB database. It
revealed ten genotypes, including ToxoDB PCR-RFLP genotypes #6 (n = 2), #19 (n =
1), #21 (n = 2), #111 (n = 2), #152 (n = 1), and #175 (n = 1) and four new types
not described before. Our results confirmed a high genetic diversity of this
parasite in southern Brazil and also showed that the use of two serological tests
in combination can improve the chance of T. gondii isolation. More studies should
be taken to determine the zoonotic potential of chickens in the transmission of
T. gondii.
PMID- 29344804
TI - Influence of highly concentrated fluoride dentifrices on remineralization
characteristics of enamel in vitro.
AB - OBJECTIVES: The aim of this in vitro study was to evaluate the role of highly
fluoridated dentifrice on remineralization characteristics of lowly and highly
pre-demineralized enamel artificial caries lesions. METHODS: Bovine enamel
specimens were prepared (pH 4.95; 21 days) and discriminated in either lowly [L]
or highly [H] pre-demineralized artificial caries lesions. Specimens with a mean
DeltaZbaseline,L (95% CI) of 5120 (4995; 5245) vol.% * MUm and a mean
DeltaZbaseline,H of 8187 (8036; 8339) vol.% * MUm were selected and randomly
allocated to 12 groups (n = 20). Treatments during pH-cycling (28 days; 6 * 60
min demineralization/day) were brushing 2*/day with fluoride-free (0 ppm F-
[L0/H0]), 1100 ppm F- [L1100/H1100], 2800 ppm F- [L2800/H2800], 5000 ppm F-
[L5000/H5000], 5000 ppm F- + glycerin [L5000 + glycerin/H5000 + glycerin], and
5000 ppm F- + TCP [L5000 + TCP/H5000 + TCP] containing dentifrices. Dentifrice
slurries were prepared with deionized water (1:3wt/wt). After cycling specimens
presenting lesion surface loss were discarded and for the remaining 202
specimens, transversal microradiographic (TMR) analyses (DeltaZpH-cycle/LDpH
cycle) were performed again. Changes in mineral loss (DeltaDeltaZ =
DeltaZbaseline - DeltaZpH-cycle) and lesion depth (DeltaLD = LDbaseline - LDpH
cycle) were calculated. RESULTS: Significant differences for DeltaDeltaZ could be
found between L0, L1100, and L5000 as well as H0, H1100, and H2800/H5000 (p <=
0.01; ANCOVA). Except for 0 ppm F-, higher DeltaDeltaZ could be found in highly
compared with lowly demineralized specimens (p <= 0.004; ANCOVA). After pH
cycling, a second lesion front could only be observed in H5000 and H5000 + TCP.
The correlation between DeltaDeltaZ and F- was moderate for lowly and highly
demineralized lesions (rL = 0.591; pL < 0.001; rH = 0.746; pH < 0.001),
indicating a fluoride dose response for both. CONCLUSION: For both baseline
substrate conditions, a dose response for fluoride could be revealed. CLINICAL
SIGNIFICANCE: Remineralization characteristics of enamel directly depended on
baseline mineral loss.
PMID- 29344805
TI - Salivary biomarkers for oral cancer and pre-cancer screening: a review.
AB - OBJECTIVE: The objective of the study was to conduct a systematic review of the
literature assessing potential salivary biomarkers of oral cancer and pre-cancer
and discuss emerging issues and challenges in relation to oral cancer and pre
cancer diagnostics. MATERIALS AND METHODS: Search for articles involved the
Medline, PubMed, and EMBASE. Specific terms were used from January 1995 to March
2017 by three experts. RESULTS: This search collected 270 articles, of which 105
articles such as reviews, case reports, news, letter to editor, etc. in first
round and 117 articles such as publications in other languages than English, non
human studies, etc. were excluded. The remaining 48 articles considered analyzing
whole saliva as well as specific gland saliva. Thirty-one studies considered oral
stimuli such as eating, drinking, and oral hygiene practices for varied periods
of time prior to sample collection. The time of collection of saliva was morning
in most studies, but the exact time of collection was not mentioned. Three
studies showed to have evaluated the whole saliva without centrifugation. Two
dimensional gel electrophoresis and tandem mass spectrometry were the most
commonly used methods. Most of the potential salivary biomarkers of oral cancer
are salivary proteins. CONCLUSION: Combination approach of salivary biomarkers
could be used as screening tool to improve early detection and diagnostic
precision of oral pre-cancer and cancer. CLINICAL RELEVANCE: The current findings
are of importance for clinicians and researchers to mitigate the challenges in
salivary-based diagnosis of oral cancer and to evaluate reliable, specific, and
sensitive salivary biomarkers for oral pre-cancer and cancer diagnosis.
PMID- 29344806
TI - Comparison of two observational methods, scanning electron and confocal laser
scanning microscopies, in the adhesive interface analysis of endodontic sealers
to root dentine.
AB - OBJECTIVES: To compare the accuracy of confocal laser scanning microscopy (CLSM)
and scanning electron microscopy (SEM) during the analysis of the adhesive
interface integrity and intratubular penetration of root canal sealers to
radicular dentine. MATERIALS AND METHODS: Twenty roots of human maxillary
incisors were prepared and distributed into two groups (n = 10), followed by
filling with gutta-percha and Endofill (G1) or AH Plus (G2). After 7 days, roots
were sectioned and analyzed under CLSM and SEM. Score systems were used to
evaluate the adhesive interface integrity (0-4) and sealer intratubular
penetration (0-3). Data were submitted to Wilcoxon-Mann-Whitney and Kendall
correlation statistical tests (alpha = 5%). RESULTS: In the adhesive interface
analysis, CLSM was similar (P = 0.157) to SEM for Endofill; however, the results
were different for AH Plus (P = 0.029). Intratubular penetration had significant
difference between observational methods for both sealers (P < 0.0001).
Correlation analysis between SEM and CLSM for adhesive interface was moderate for
Endofill and low for AH Plus. Intratubular penetration was low for both sealers.
CONCLUSION: SEM and CLSM analysis had similar results when sealers were compared,
with a more homogeneous adhesive interface, and greater intratubular penetration
for AH Plus. Comparison between observational methods demonstrated low positive
correlation for adhesive interface and intratubular penetration analysis.
CLINICAL RELEVANCE: A proper interface formed between sealer and dentine is very
important for final quality of root canal filling. Observational methods which
allow an accurate analysis of this interface must be selected to assess such
features.
PMID- 29344807
TI - Inhibition of bone resorption by bisphosphonates interferes with orthodontically
induced midpalatal suture expansion in mice.
AB - OBJECTIVES: Craniofacial sutures are important growth sites for skull development
and are sensitive to mechanical stress. In order to determine the role of bone
resorption in stress-mediated sutural bone growth, midpalatal suture expansion
was performed in mice receiving alendronate, an anti-resorptive bisphosphonate.
MATERIALS AND METHODS: The midpalatal sutures of 8-week-old C57BL/6 mice were
expanded by orthodontic wires over the period of 2 weeks. Mice with maxillary
expansion without drug treatment as well as untreated animals served as controls.
Skulls were analyzed with micro-computed tomography (micro-CT),
immunohistochemistry and histology. RESULTS: Maxillary expansion in mice without
drug treatment resulted in an increase of TRAP-positive osteoclasts. In contrast,
no increase in osteoclasts was observed in expanded sutures of mice with
bisphosphonate treatment. Double calcein labeling demonstrated rapid bone
formation on the oral edges of the expanded sutures in mice without
bisphosphonate treatment. Less bone formation was observed in bisphosphonate
treated mice after expansion. Histology revealed that the sutural architecture
was reestablished in expanded sutures of mice without bisphosphonate treatment.
In contrast, the sutural architecture was disorganized and the cartilage had an
irregular form, following expansion in bisphosphonate-treated mice. Finally,
micro-CT imaging demonstrated that the total amount of maxillary expansion was
significantly lower in mice with bisphosphonate treatment as compared to those of
mice without drug treatment. CONCLUSIONS: In conclusion, our results indicate
that osteoclast-mediated bone resorption is needed for maxillary suture expansion
and reorganization of sutural architecture. CLINICAL SIGNIFICANCE: Orthodontic
palatal expansion can be complicated in patients with inherited or drug-induced
diseases of osteoclast dysfunction.
PMID- 29344808
TI - Minimally Invasive Esophagectomy with Thoracic Duct Resection Post Neoadjuvant
Chemoradiotherapy for Carcinoma Esophagus-Impact on Lymph Node Yield and
Hemodynamic Parameters.
AB - BACKGROUND: Neoadjuvant therapy followed by surgery is the current recommended
treatment for locally advanced esophageal carcinoma. Thoracic duct (TD) resection
was indicated for radical mediastinal lymphadenectomy. However, TD resection can
cause hemodynamic disturbances. The presence of metastasis in TD has not been
previously studied. METHODS: Twenty-two patients who underwent minimally invasive
esophagectomy with D2 lymphadenectomy after neoadjuvant chemoradiotherapy for
esophageal squamous cell carcinoma were analyzed. Ten patients had their TD
resected from thoracic inlet till the esophageal hiatus. Multiple
histopathological sections of the TD were examined for evidence of tumor spread.
Intraoperative and immediate (48 h) postoperative hemodynamic parameters, lymph
node yield, and postoperative morbidity were compared between TD-resected and TD
preserved groups. RESULTS: The median postoperative day 1 fluid requirement (3310
mL vs. 2875 mL, P = 0.059) and the median postoperative day 2 pulse rate were
higher in the TD-resected group (111/min vs. 95/min, P = 0.043). There was no
significant difference in the intraoperative fluid infusion, blood loss, urine
output, mean blood pressure, pulse rate, postoperative urine output, and mean
blood pressure between two groups. Median (range) mediastinal lymph node count
was similar in TD-resected and TD-preserved groups [15(11-32) vs. 14(9-31), P =
0.283]. Pathological examination of TD did not reveal tumor cells in any of the
patients. There was no significant difference in the postoperative morbidity
between two groups except for cervical anastomotic dehiscence (P = 0.007).
CONCLUSIONS: Minimally invasive esophagectomy with TD resection causes minor
hemodynamic changes in the immediate postoperative period, without adversely
affecting the postoperative outcome. In the setting of neoadjuvant
chemoradiotherapy, TD resection does not increase lymph node yield.
PMID- 29344809
TI - Regeneration of functional alveoli by adult human SOX9+ airway basal cell
transplantation.
AB - Irreversible destruction of bronchi and alveoli can lead to multiple incurable
lung diseases. Identifying lung stem/progenitor cells with regenerative capacity
and utilizing them to reconstruct functional tissue is one of the biggest hopes
to reverse the damage and cure such diseases. Here we showed that a rare
population of SOX9+ basal cells (BCs) located at airway epithelium rugae can
regenerate adult human lung. Human SOX9+ BCs can be readily isolated by
bronchoscopic brushing and indefinitely expanded in feeder-free condition.
Expanded human SOX9+ BCs can give rise to alveolar and bronchiolar epithelium
after being transplanted into injured mouse lung, with air-blood exchange system
reconstructed and recipient's lung function improved. Manipulation of lung
microenvironment with Pirfenidone to suppress TGF-beta signaling could further
boost the transplantation efficiency. Moreover, we conducted the first autologous
SOX9+ BCs transplantation clinical trial in two bronchiectasis patients. Lung
tissue repair and pulmonary function enhancement was observed in patients 3-12
months after cell transplantation. Altogether our current work indicated that
functional adult human lung structure can be reconstituted by orthotopic
transplantation of tissue-specific stem/progenitor cells, which could be
translated into a mature regenerative therapeutic strategy in near future.
PMID- 29344810
TI - Dehydroepiandrosterone (DHEA) supplementation: an underappreciated cause of
premature progesterone elevation detected during frozen embryo transfer.
PMID- 29344811
TI - Metabolic evolution and a comparative omics analysis of Corynebacterium
glutamicum for putrescine production.
AB - Putrescine is widely used in the industrial production of bioplastics,
pharmaceuticals, agrochemicals, and surfactants. Because the highest titer of
putrescine is much lower than that of its precursor L-ornithine reported in
microorganisms to date, further work is needed to increase putrescine production
in Corynebacterium glutamicum. We first compared 7 ornithine decarboxylase genes
and found that the Enterobacter cloacae ornithine decarboxylase gene speC1 was
most suitable for putrescine production in C. glutamicum. Increasing NADPH
availability and blocking putrescine oxidation and acetylation were chosen as
targets for metabolic engineering. The putrescine producer C. glutamicum PUT4 was
first constructed by deleting puo, butA and snaA genes, and replacing the fabG
gene with E. cloacae speC1. After adaptive evolution with C. glutamicum PUT4, the
evolved strain C. glutamicum PUT-ALE, which produced an 96% higher amount of
putrescine compared to the parent strain, was obtained. The whole genome
resequencing indicates that the SNPs located in the odhA coding region may be
associated with putrescine production. The comparative proteomic analysis reveals
that the pentose phosphate and anaplerotic pathway, the glyoxylate cycle, and the
ornithine biosynthetic pathway were upregulated in the evolved strain C.
glutamicum PUT-ALE. The aspartate family, aromatic, and branched chain amino acid
and fatty acid biosynthetic pathways were also observed to be downregulated in C.
glutamicum PUT-ALE. Reducing OdhA activity by replacing the odhA native start
codon GTG with TTG and overexpression of cgmA or pyc458 further improved
putrescine production. Repressing the carB, ilvH, ilvB and aroE expression via
CRISPRi also increased putrescine production by 5, 9, 16 and 19%, respectively.
PMID- 29344812
TI - Short-term and long-term effects of osteoporosis on incisor teeth and femoral
bones evaluated by Raman spectroscopy and energy dispersive X-ray analysis in
ovariectomized rats.
AB - There are few published data on the relationship between loss of bone mass due to
osteoporosis and poor tooth quality. This study analyzed the effects of
osteoporosis on incisor teeth and femoral bones using optical techniques in rats.
Twenty female Wistar rats aged 6 months (n = 20) were randomized into two groups:
control group, non-ovariectomized rats (n = 10); ovariectomy group,
ovariectomized rats to induce osteoporosis (n = 10). Each group was subdivided
randomly into two groups containing five rats each as follows. Control group 1:
non-ovariectomized rats euthanized at the age of 9 or 3 months post-ovariectomy
(n = 5); Control group 2: non-ovariectomized rats euthanized at the age of 1 year
or 6 months post-ovariectomy (n = 5); ovariectomy group 1: ovariectomized rats
euthanized at the age of 9 months or 3 months post-ovariectomy (n = 5);
ovariectomy group 2: ovariectomized rats euthanized at the age of 1 year or 6
months post-ovariectomy (n = 5). The incisor teeth and femoral bones of Wistar
rats were removed to perform Raman spectroscopy using an excitation laser at 785
nm. In addition, an energy-dispersive X-ray spectrometer system was used to
evaluate calcium (Ca) and phosphorus (P). The main findings included significant
changes (p < 0.05) for phosphate and carbonate band areas for both incisor teeth
and femur bones. In addition, there was significant negative correlation between
the P concentration and phosphate/carbonate ratio (lower P content-larger ratio,
p < 0.05) for incisor teeth and femoral bones. The proline and CH2 wag band areas
were significantly reduced only for the incisor teeth (p < 0.05). Therefore,
Raman spectroscopy assessed the compositional, physicochemical and structural
changes in hard tissue. The current study also pointed out the possible action
mechanisms of these changes, bone fracture risk and dental fragility. It is
important to emphasize that poor dental quality may also occur due to
osteoporosis.
PMID- 29344813
TI - Stroke volume variation and serum creatinine changes during abdominal aortic
aneurysm surgery: a time-integrated analysis.
AB - BACKGROUND: Patients undergoing abdominal aortic aneurysm (AAA) surgery with
suprarenal clamping are at high risk for acute kidney injury (AKI) and major
cardiac and cerebrovascular events (MACCE). We aimed to assess whether the stroke
volume variation (SVV), a measure of hemodynamic instability, is associated with
AKI in hypertensive patients undergoing elective AAA surgery with suprarenal
clamping. METHODS: In a cohort of 51 hypertensive patients, we performed serial
measurements of SVV (n = 459) and serum creatinine (sCr) (n = 255). AKI was
defined according to the KDIGO clinical practice guidelines. Data were analyzed
by repeated-measures ANOVA and regression analysis of time-integrated changes of
both SVV and sCr. RESULTS: AKI developed in 45% of patients (stage 1: 31%; stage
2: 10%; stage 3: 2%). The diuresis during surgery (beta - 0.29 Z-score 95% [CI -
0.54, - 0.05]; p = 0.02), clamp time (beta 0.29 Z-score [0.05-0.52]; p = 0.02),
and time-integrated changes in SVV from baseline to 12 h after surgery (beta 0.31
Z-score [0.03-0.60]; p = 0.03) were independent predictors of the time-integrated
changes in sCr from baseline to 48 h after the end of surgery. In a model
adjusted for age and sex, patients with AKI had an increased risk for MACCE
during a mean follow-up of 3.5 +/- 1.1 years (HR 5.53 [1.52-20.06]; p = 0.004).
CONCLUSIONS: SVV increases progressively during and after AAA surgery in subjects
who will develop AKI. The increase of SVV precedes and predicts the rise in sCr
and is a good discriminator of the development of AKI. AKI is associated with an
increased long-term risk for MACCE.
PMID- 29344814
TI - Nutritional therapy in autosomal dominant polycystic kidney disease.
AB - CKD-related nutritional therapy (NT) is a crucial cornerstone of CKD patients'
treatment, but the role of NT has not been clearly investigated in autosomal
dominant polycystic kidney disease (ADPKD). Several clinical studies have focused
on new pharmacological approaches to delay cystic disease progression, but there
are no data on dietary interventions in ADPKD patients. The aim of this paper is
to analyze the evidence from the literature on the impact of five nutritional
aspects (water, sodium, phosphorus, protein intake, and net acid load) in CKD
related ADPKD extrapolating-where information is unavailable-from what occurs in
CKD non-ADPKD patients Sodium intake restriction could be useful in decreasing
the growth rate of cysts. Although further evidence is needed, restriction of
phosphorus and protein intake restriction represent cornerstones of the dietary
support of renal non-ADPKD patients and common sense can guide their use. It
could be also helpful to limit animal protein, increasing fruit and vegetables
intake together with a full correction of metabolic acidosis. Finally, fluid
intake may be recommended in the early stages of the disease, although it is not
to be prescribed in the presence of moderate to severe reduction of renal
function.
PMID- 29344815
TI - Comment on: "Genetic Variants and Anterior Cruciate Ligament Rupture: A
Systematic Review".
PMID- 29344816
TI - Author's Reply to Lv: Comment on: "Genetic Variants and Anterior Cruciate
Ligament Rupture: A Systematic Review".
PMID- 29344817
TI - The Content of Mercury in Herbal Dietary Supplements.
AB - The dietary supplement market in Poland has been growing rapidly, and the number
of registered products and their consumption increases steadily. Among the most
popular and the easiest to get are herbal supplements, available in any
supermarket. The aim of this paper was to investigate the mercury content in the
herbal supplements. The dietary supplements that have been examined (24) are
available on the Polish market and contain one or more herbal ingredients.
Supplements were pulverized in porcelain mortar and identified by AMA 254 atomic
absorption spectrometer. The range of variations for all tested supplements was
within 0.02-4293.07 MUg/kg. The arithmetic mean of the total result was 193.77
MUg/kg. A higher mercury content then this mean was found in preparations-bamboo
shoots and alga Chlorella pyrenoidosa. The studies have shown that mercury is
present in every examined herbal supplement, and its content exceeds in two
preparations (with bamboo and alga) the permissible limit of 0.10 mg/kg. There
were statistically significant differences in the occurrence of mercury depending
on the herbal ingredient in the supplement. The lowest content was found in the
preparation with Tanacetum parthenium and the highest with bamboo shoots. The
mercury content in the tested herbal supplements was statistically significant in
the form of a supplement-a tablet and a capsule. Daily, weekly, monthly, and
yearly consumption of mercury with examined supplements was calculated-the
results did not exceed the PTWI-provisional tolerable weekly intake of mercury.
To increase consumer safety, it is imperative to conduct further research on
dietary supplements and implement a stricter quality control of the dietary
supplements.
PMID- 29344818
TI - Dietary Chromium Picolinate Supplementation Affects Growth, Whole-Body
Composition, and Gene Expression Related to Glucose Metabolism and Lipogenesis in
Juvenile Blunt Snout Bream, Megalobrama amblycephala.
AB - An 11-week feeding trial was carried out to investigate the effects of
supplemented chromium picolinate (Cr-Pic) on the growth, whole-body composition,
and relative mRNA expression related to lipogenesis and glucose metabolism in
juvenile blunt snout bream. Seven isonitrogenous and isoenergetic diets with
graded Cr supplementation levels were fed to triplicate groups. The final weight
(FW), feed conversion ratio (FCR), and specific growth rate (SGR) were improved
with increasing dietary Cr supplementation levels up to 0.4 mg/kg, and thereafter
showed relatively constant. However, 12.0 mg/kg dietary Cr supplementation
decreased growth and feed utilization. Based on SGR and FCR, the optimal dietary
Cr supplementation level for the juvenile was estimated to be 0.28 mg/kg.
Significantly higher plasma insulin levels were found in juvenile fed diets with
0.4 and 0.8 mg/kg Cr supplementation compared to those fed diet sans supplemented
Cr. Plasma glucose levels decreased with increasing dietary Cr supplementation,
and the lowest value was remarked in the group added 3.2 mg/kg of Cr. Adding 0.4
0.8 mg/kg Cr enhanced insulin receptor substrate 1 (IRS-1), phosphoinositide-3
kinase (PI3K), and pyruvate kinase (PK) and inhibited expression of
phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), and
glycogen synthase (GS) mRNA levels. High dietary Cr (12.0 mg/kg) supplementation
resulted in high G6Pase and PEPCK expression. The highest content of whole-body
lipid was remarked in fish fed with 0.4 mg/kg dietary Cr, which related to the
enhanced gene expression related to lipogenesis; thereafter, mRNA levels showed a
diminishing trend. These findings indicate that optimum dietary Cr-Pic
supplementation has a positive effect on growth and blood glucose homeostasis by
modifying the mRNA levels related to glucose metabolism and lipogenesis in
juvenile blunt snout bream.
PMID- 29344820
TI - Metastases from distant primary tumours on the head and neck: clinical
manifestation and diagnostics of 91 cases.
AB - PURPOSE: The aim of this study was to evaluate which primary tumours metastasize
on the head and neck region, identify the kind of clinical manifestation, the
types of diagnostics that should be performed, and prove that the therapy appears
possible and useful. PATIENTS: As many as 91 patients with a distant metastasis
on the head and neck were enrolled in this retrospective clinical study from
January 2004 to September 2016. All the patients were evaluated for clinical
symptoms, primary tumour, localization, diagnostics, and surgical procedure.
RESULTS: A total of 31 patients had asymptomatic swelling, 27 patients had
symptomatic swelling, and nine experienced isolated pain without swelling. Most
other symptoms were organ-specific. The most frequent localizations were the
orbit (44 metastases), mandible (19), neck region (9), and skin (7). The most
common primary tumours were breast carcinoma (44), bronchial carcinoma (12), and
renal carcinoma (9). A biopsy was performed on 38 patients, a partial resection
was done on 28 patients, extirpation on six patients, and a radical resection on
19 patients. CONCLUSION: Distant metastases on the head and neck are rare and,
therefore, pose a challenge for the oncologist and other involved disciplines.
Most distant metastases occur within the first five years. Late metastases,
especially in breast carcinoma, are still possible after 20 years. A surgical
examination should be carried out if the findings are not clear due to multiple
differential diagnoses. In particular, surgical options under palliative aspects
should be examined.
PMID- 29344821
TI - Resistance of four fixation techniques used to treat subcondylar fractures.
AB - OBJECTIVE: This study aimed to evaluate the resistance of four fixation
techniques used to treat subcondylar fractures. The following techniques were
evaluated: fixation with one 4-hole single straight plate; fixation with one 2-mm
4-hole system plate and one 1.5-mm 3-hole system plate; fixation with two 2-mm
plates with a 3-hole anterior plate; and fixation with two 2-mm plates with four
holes each. STUDY DESIGN: Each fixation technique was subjected to a resistance
test. The load values were measured when displacement of 1, 2, and 5 mm was
reached. Load values were compared for statistically significant differences
using analysis of variance (ANOVA; p < 0.5) and Tukey's test. RESULTS:
Statistically significant differences were observed, when the load was applied to
the first molar on the side of the fracture. The group treated with a 4-hole, 2
mm, one plate system showed resistance to lower load values than the groups
treated with two plates in any combination. CONCLUSIONS: When the fracture was
fixed using two plates, regardless of the kind of plates used, no statistically
significant difference between the groups was observed. However, two plate
systems showed better resistance than one plate systems.
PMID- 29344822
TI - Novel oral anticoagulants in the preoperative period: a meta-analysis.
AB - The purpose of this study is to evaluate the efficacy and safety of novel oral
anticoagulant (NOAC) versus warfarin therapy in patients undergoing different
operations. We performed a systematic review of MEDLINE, EMBASE, Cochrane
Controlled Trials Register, and reports presented at scientific meetings. The
efficacy and safety of NOACs during the perioperative period was compared to that
using warfarin. Of the 2652 studies initially reviewed, we identified 9 that
included 15,880 patients for the meta-analysis. Compared to warfarin, dabigatran
increased the risk of major bleeding (RR 1.37, 95% CI 1.06-1.78, P = 0.02).
Apixaban (RR 0.63, 95% CI 0.40-0.99, P = 0.04) reduced thrombotic events. NOAC
therapy decreased thrombotic events in patients undergoing non-cardiac surgery
(RR 0.68, 95% CI 0.50-0.92, P = 0.02). Compared to warfarin, the administration
of NOACs in the perioperative period has the same risk of thromboembolism and
major bleeding. But patients undergoing non-cardiac surgery may benefit more from
perioperative NOAC therapy. Apixaban may reduce thrombotic events and dabigatran
increases the risk of major bleeding during the perioperative period.
PMID- 29344823
TI - Long-term visual outcomes of craniopharyngioma in children.
AB - Visual function is a critical factor in the diagnosis, monitoring, and prognosis
of craniopharyngiomas in children. The aim of this study was to report the long
term visual outcomes in a cohort of pediatric patients with craniopharyngioma.
The study design is a retrospective chart review of craniopharyngioma patients
from a single tertiary-care pediatric hospital. 59 patients were included in the
study. Mean age at presentation was 9.4 years old (range 0.7-18.0 years old). The
most common presenting features were headache (76%), nausea/vomiting (32%), and
vision loss (31%). Median follow-up was 5.2 years (range 1.0-17.2 years). During
follow-up, visual decline occurred in 17 patients (29%). On Kaplan Meier survival
analysis, 47% of the cases of visual decline occurred within 4 months of
diagnosis, with the remaining cases occurring sporadically during follow-up (up
to 8 years after diagnosis). In terms of risk factors, younger age at diagnosis,
optic nerve edema at presentation, and tumor recurrence were found to have
statistically significant associations with visual decline. At final follow-up,
58% of the patients had visual impairment in at least one eye but only 10% were
legally blind in both eyes (visual acuity 20/200 or worse or < 20 degrees of
visual field). Vision loss is a common presenting symptom of craniopharyngiomas
in children. After diagnosis, monitoring vision is important as about 30% of
patients will experience significant visual decline. Long-term vision loss occurs
in the majority of patients, but severe binocular visual impairment is uncommon.
PMID- 29344824
TI - Brucellosis Risk in Urban and Agro-pastoral Areas in Tanzania.
AB - Epidemiology of human and animal brucellosis may depend on ecological conditions.
A cross-sectional study was conducted to compare prevalence and risk factors of
bovine brucellosis, and risky behaviours for the human infection between urban
and agro-pastoral areas in Morogoro region, Tanzania. Cattle blood sampling and
interviews using a structured questionnaire were conducted with farmers. Rose
Bengal test was conducted for the cattle sera, and positive samples were
confirmed with competitive ELISA. Farm-level sero-prevalences were 0.9% (1/106,
95% CI 0.0-5.9%) and 52.9% (9/17, 95% CI 28.5-76.1%) in urban and agro-pastoral
areas, respectively. The animal-level-adjusted prevalences were 0.2% (1/667, 95%
CI 0.0-1.1%) and 7.0% (28/673, 95% CI 5.7-8.4%) in those areas. The final farm
level model including both areas found two risk factors: history of abortion in
the herd (P < 0.01) and cattle grazing (P = 0.07). The animal-level risk factors
in agro-pastoral areas were age (P = 0.04) and history of abortion (P = 0.03). No
agro-pastoral farmer knew about Brucella vaccine. Agro-pastoralists generally had
poorer knowledge on brucellosis and practiced significantly more risky behaviours
for human brucellosis such as drinking raw milk (17.6%, P < 0.01) and blood
(35.3%, P < 0.01), and helping cattle birth (100%, P = 0.04) than urban farmers
(0, 0 and 79.2%, respectively). Intervention programs through education including
both human and animal health particularly targeting agro-pastoralists would be
needed.
PMID- 29344825
TI - The Voltage-Dependent Anion Channel (VDAC) of Pacific Oysters Crassostrea gigas
Is Upaccumulated During Infection by the Ostreid Herpesvirus-1 (OsHV-1): an
Indicator of the Warburg Effect.
AB - Voltage-dependent anion channel (VDAC) is a key mitochondrial protein. VDAC
drives cellular energy metabolism by controlling the influx and efflux of
metabolites and ions through the mitochondrial membrane, playing a role in its
permeabilization. This protein exerts a pivotal role during the white spot
syndrome virus (WSSV) infection in shrimp, through its involvement in a
particular metabolism that plays in favor of the virus, the Warburg effect. The
Warburg effect corresponds to an atypical metabolic shift toward an aerobic
glycolysis that provides energy for rapid cell division and resistance to
apoptosis. In the Pacific oyster Crassostrea gigas, the Warburg effect occurs
during infection by Ostreid herpesvirus (OsHV-1). At present, the role of VDAC in
the Warburg effect, OsHV-1 infection and apoptosis is unknown. Here, we developed
a specific antibody directed against C. gigas VDAC. This tool allowed us to
quantify the tissue-specific expression of VDAC, to detect VDAC oligomers, and to
follow the amount of VDAC in oysters deployed in the field. We showed that
oysters sensitive to a mortality event in the field presented an accumulation of
VDAC. Finally, we propose to use VDAC quantification as a tool to measure the
oyster susceptibility to OsHV-1 depending on its environment.
PMID- 29344826
TI - Phytochemical Analysis and Evaluation of the Antioxidant, Anti-Inflammatory, and
Antinociceptive Potential of Phlorotannin-Rich Fractions from Three Mediterranean
Brown Seaweeds.
AB - Phlorotannins, phenolic compounds produced exclusively by seaweeds, have been
reported to possess various pharmacological properties. However, there have been
few works on these compounds from Mediterranean seaweeds. In this study, we
investigated the phytochemical analysis and pharmacological potential of
phlorotannin-rich fractions from three brown seaweeds collected along the Tunisia
coast: Cystoseira sedoides (PHT-SED), Cladostephus spongeosis (PHT-CLAD), and
Padina pavonica (PHT-PAD). Phytochemical determinations showed considerable
differences in total phenolic content (TPC) and phlorotannin content (PHT). The
highest TPC level (26.45 mg PGE/g dry material (Dm)) and PHT level (873.14 MUg
PGE/g Dm) were observed in C. sedoides. The antioxidant properties of these three
fractions assessed by three different methods indicated that C. sedoides
displayed the highest total antioxidant activity among the three species (71.30
mg GAE/g Dm), as well as the free radical scavenging activity with the lowest
IC50 value in both DPPH (27.7 MUg/mL) and ABTS (19.1 MUg/mL) assays. Furthermore,
the pharmacological screening of the anti-inflammatory potential of these
fractions using in vivo models, in comparison to reference drugs, established a
remarkable activity of PHT-SED at the dose of 100 mg/kg; the inhibition
percentages of ear edema in mice model and paw edema in rats model were of 82.55
and 81.08%, respectively. The content of malondialdehyde (MDA) in liver tissues
has been quantified, and PHT-SED was found to remarkably increase the lipid
peroxidation in rat liver tissues. In addition, in two pain mice models, PHT-SED
displayed a profound antinociceptive activity at 100 mg/kg and has proved a
better analgesic activity when used in combination with the opioid drug,
tramadol.
PMID- 29344828
TI - Neuroprotective effect of p-coumaric acid in mice with cerebral ischemia
reperfusion injuries.
AB - Cerebral ischemia reperfusion (IR) is associated with neuronal death, which leads
to disability and cognitive decline. The pathomechanism occurs because ischemia
is exacerbated during the reperfusion period. Neuronal damage susceptibility
depends on the affected brain areas and the duration of ischemia. Prevention and
supplementation to neurons may help them endure during IR and further benefit
them in rehabilitation. We investigated the protective effect of p-coumaric acid
(PC) on cerebral IR injuries in mice. We randomly divided 30 male ICR mice into 3
groups of Sham (received vehicle and not induced IR), Control-IR (received
vehicle and induced IR) and PC-IR (received 100 mg/kg PC and induced IR). We
orally administered vehicle or 100 mg/kg of p-coumaric acid for 2 weeks before
inducing the cerebral IR injuries by using 30 min of a bilateral common carotid
artery occlusion followed by a 45-min reperfusion. We induced the IR condition in
the Control-IR and PC-IR groups but not the Sham group, and only the PC-IR group
received p-coumaric acid. After IR induction, we sacrificed all the mice and
collected their brain tissues to evaluate their oxidative statuses, whole brain
infarctions and vulnerable neuronal deaths. We studied the whole-brain infarction
volume by 2, 3, 5-triethyltetrazoliumchloride staining of sections. We performed
a histological investigation of the vulnerable neuronal population in the dorsal
hippocampus by staining brain sections with 0.1% cresyl violet. The results
indicated that IR caused significant increases in calcium and malondialdehyde
(MDA) levels, whole brain infarction volume and hippocampal neuronal death.
Pretreatment with p-coumaric acid significantly reduced MDA levels, whole-brain
infarction volume and hippocampal neuronal death together and increased catalase
and superoxide dismutase activities. We conclude here that pretreating animals
with p-coumaric acid can prevent IR-induced brain oxidative stress, infarction
size and neuronal vulnerability to death in cerebral IR injuries.
PMID- 29344829
TI - Rapid-acting and Regular Insulin are Equal for High Fat-Protein Meal in
Individuals with Type 1 Diabetes Treated with Multiple Daily Injections.
AB - INTRODUCTION: The fat and protein content can impact late postprandial glycemia;
therefore, prolonged insulin boluses for high-fat/-protein meals are recommended
for patients with type 1 diabetes on insulin pump therapy. It is not clear how to
translate these findings to multiple daily injection (MDI) therapy. We
hypothesized that regular insulin with a slower onset and a longer duration of
action might be advantageous for such meals. METHODS: Twenty-five patients with
well-controlled type 1 diabetes (mean HbA1c 6.8%, 51 mmol/mol, no episodes of
hypoglycemia) on MDI therapy, aged 27.9 +/- 4.3 years and well trained in
flexible intensive insulin therapy, were given three test breakfasts with the
same carbohydrate (CHO) content. The amount of fat and protein was low (LFP) or
high (HFP). For LFP meals, patients received a rapid-acting insulin; for HFP
meals, a rapid-acting or regular insulin was given in individual doses according
to the CHO content and individual insulin-CHO ratios. Postprandial glycemia was
determined by 6-h continuous glucose monitoring. RESULTS: Acute postprandial
glucose levels measured for 2 h were similar after LFP and two HFP meals (7.8 +/-
2.0, 8.1 +/- 2.1, 8.0 +/- 1.9 mmol/l). Late postprandial glycemia measured from 2
to 6 h was significantly lower after the LFP meal (6.7 +/- 1.8 mmol/l, p < 0.05)
than after the HFP meals, but there was no difference between the rapid-acting or
regular insulin on HFP days (8.6 +/- 2.6 and 8.9 +/- 2.8 mmol/l, NS). CONCLUSION:
The preliminary results of this study indicate no benefit to cover fat-protein
meals with regular insulin in individuals with type 1 diabetes treated with MDI.
PMID- 29344827
TI - Molecular imaging of cardiac remodelling after myocardial infarction.
AB - Myocardial infarction and subsequent heart failure is a major health burden
associated with significant mortality and morbidity in western societies. The
ability of cardiac tissue to recover after myocardial infarction is affected by
numerous complex cellular and molecular pathways. Unbalance or failure of these
pathways can lead to adverse remodelling of the heart and poor prognosis. Current
clinical cardiac imaging modalities assess anatomy, perfusion, function, and
viability of the myocardium, yet do not offer any insight into the specific
molecular pathways involved in the repair process. Novel imaging techniques allow
visualisation of these molecular processes and may have significant diagnostic
and prognostic values, which could aid clinical management. Single photon
emission tomography, positron-emission tomography, and magnetic resonance imaging
are used to visualise various aspects of these molecular processes. Imaging
probes are usually attached to radioisotopes or paramagnetic nanoparticles to
specifically target biological processes such as: apoptosis, necrosis,
inflammation, angiogenesis, and scar formation. Although the results from
preclinical studies are promising, translating this work to a clinical
environment in a valuable and cost-effective way is extremely challenging.
Extensive evaluation evidence of diagnostic and prognostic values in multi-centre
clinical trials is still required.
PMID- 29344830
TI - RAP2.6L and jasmonic acid-responsive genes are expressed upon Arabidopsis
hypocotyl grafting but are not needed for cell proliferation related to healing.
AB - KEY MESSAGE: Jasmonic acid and RAP2.6L are induced upon wounding but are not
involved in cell proliferation during healing in Arabidopsis hypocotyls. Plants
produce jasmonic acid in response to wounding, but its role in healing, if any,
has not been determined. Previously, the jasmonic acid-induced transcription
factor, RAP2.6L, related to APETALA 2.6-like, was identified as a spatially
expressed factor involved in tissue reunion in partially incised flowering stems
of Arabidopsis. In the present study, we investigated the function of JA and
RAP2.6L on wound healing using an Arabidopsis hypocotyl-grafting system, in which
separated tissues are reattached by vascular tissue cell proliferation. The
jasmonic acid-responsive genes AOS and JAZ10 were transiently expressed
immediately after grafting. We confirmed that the endogenous content of jasmonic
acid-Ile, which is the bioactive form of jasmonic acid, increased in hypocotyls 1
h after grafting. Morphological analysis of the grafted tissue revealed that
vascular tissue cell proliferation occurred in a similar manner in wild-type
Arabidopsis, the jasmonic acid-deficient mutant aos, the jasmonic acid
insensitive mutant coi1, and in Arabidopsis that had been exogenously treated
with jasmonic acid. RAP2.6L expression was also induced during graft healing.
Because RAP2.6L expression occurred during graft healing in aos and coi1, its
expression must be regulated via a jasmonic acid-independent pathway. The rap2.6L
mutant and dominant repressor transformants for RAP2.6L showed normal cell
proliferation during graft healing. Taken together, our results suggest that JA
and RAP2.6L, induced by grafting, are not necessary for cell proliferation
process in healing.
PMID- 29344833
TI - Violence Against Women in Cambodia: Towards a Culturally Responsive Theory of
Change.
AB - Almost one in four women in Cambodia is a victim of physical, emotional or sexual
violence. This article brings together two seldom connected fields: Theory of
Change (ToC) and cultural responsiveness in international development. It applies
these approaches to a priority in global health, which is to prevent violence
against women (VAW) and, drawing on my research on the epigenesis of VAW in
Cambodia, develops an argument on the need for interventions to work with
tradition and culture rather than only highlight it in problematic terms. The
research draws on an ethnographic study carried out in Cambodia with 102
perpetrators and survivors of emotional, physical and sexual VAW and 228 key
informants from the Buddhist and healing sectors. The eight 'cultural attractors'
identified in the author's prior research highlight the cultural barriers to
acceptance of the current Theory of Change. ToC for VAW prevention in Cambodia
seems to assume that local culture promotes VAW and that men and women must be
educated to eradicate the traditional gender norms. There is a need for
interventions to work with tradition and culture rather than only highlight it in
problematic terms. The cultural epigenesis of VAW in Cambodia is an insight which
can be used to build culturally responsive interventions and strengthen the
primary prevention of VAW.
PMID- 29344832
TI - Mitogen activated protein kinase 6 and MAP kinase phosphatase 1 are involved in
the response of Arabidopsis roots to L-glutamate.
AB - KEY MESSAGE: The function and components of L-glutamate signaling pathways in
plants have just begun to be elucidated. Here, using a combination of genetic and
biochemical strategies, we demonstrated that a MAPK module is involved in the
control of root developmental responses to this amino acid. Root system
architecture plays an essential role in plant adaptation to biotic and abiotic
factors via adjusting signal transduction and gene expression. L-Glutamate (L
Glu), an amino acid with neurotransmitter functions in animals, inhibits root
growth, but the underlying genetic mechanisms are poorly understood. Through a
combination of genetic analysis, in-gel kinase assays, detailed cell elongation
and division measurements and confocal analysis of expression of auxin, quiescent
center and stem cell niche related genes, the critical roles of L-Glu in primary
root growth acting through the mitogen-activated protein kinase 6 (MPK6) and the
dual specificity serine-threonine-tyrosine phosphatase MKP1 could be revealed. In
gel phosphorylation assays revealed a rapid and dose-dependent induction of MPK6
and MPK3 activities in wild-type Arabidopsis seedlings in response to L-Glu.
Mutations in MPK6 or MKP1 reduced or increased root cell division and elongation
in response to L-Glu, possibly modulating auxin transport and/or response, but in
a PLETHORA1 and 2 independent manner. Our data highlight MPK6 and MKP1 as
components of an L-Glu pathway linking the auxin response, and cell division for
primary root growth.
PMID- 29344831
TI - Interaction network of core ABA signaling components in maize.
AB - KEY MESSAGE: We defined a comprehensive core ABA signaling network in monocot
maize, including the gene expression, subcellular localization and interaction
network of ZmPYLs, ZmPP2Cs, ZmSnRK2s and the putative substrates. The
phytohormone abscisic acid (ABA) plays an important role in plant developmental
processes and abiotic stress responses. In Arabidopsis, ABA is sensed by the PYL
ABA receptors, which leads to binding of the PP2C protein phosphatase and
activation of the SnRK2 protein kinases. These components functioning diversely
and redundantly in ABA signaling are little known in maize. Using Arabidopsis
pyl112458 and snrk2.2/3/6 mutants, we identified several ABA-responsive ZmPYLs
and ZmSnRK2s, and also ZmPP2Cs. We showed the gene expression, subcellular
localization and interaction network of ZmPYLs, ZmPP2Cs, and ZmSnRK2s, and the
isolation of putative ZmSnRK2 substrates by mass spectrometry in monocot maize.
We found that the ABA dependency of PYL-PP2C interactions is contingent on the
identity of the PP2Cs. Among 238 candidate substrates for ABA-activated protein
kinases, 69 are putative ZmSnRK2 substrates. Besides homologs of previously
reported putative AtSnRK2 substrates, 23 phosphoproteins have not been discovered
in the dicot Arabidopsis. Thus, we have defined a comprehensive core ABA
signaling network in monocot maize and shed new light on ABA signaling.
PMID- 29344834
TI - Employment Rates in Flexible Assertive Community Treatment Teams in The
Netherlands: An Observational Study.
AB - We determined the proportions of clients treated in Flexible Assertive Community
Treatment teams who were unemployed and gained employment and who were employed
and lost employment. Secondly, we explored the demographical and clinical factors
associated with employment. Data were collected during routine outcome
monitoring. We calculated differences in employment rates over a year and
explored differences in demographic characteristics at baseline between patient
groups. Logistic regression analysis was used to estimate the role of clinical
predictor variables on employment status. Over time, 10% remained employed, 5%
lost their employment, 3% gained employment and 82% remained unemployed. Clients
who found employment were younger, more often male, and had significantly fewer
psychosocial problems and a higher subjective quality of life during follow-up
than those who remained unemployed. Problems with motivation for treatment at
baseline were related to losing employment or remaining unemployed. Better
implementation of vocational services is very important for increasing the number
of clients gaining employment.
PMID- 29344835
TI - Genetic Evidence for the Role of a Rice Vacuolar Invertase as a Molecular Sink
Strength Determinant.
AB - BACKGROUND: Rice is a major crop feeding the majority of the global population,
and increasing its sink strength is one of the modes to alleviate the declining
availability of food for the rapidly growing world population. We demonstrate a
role for an important rice vacuolar invertase isoform, OsINV3, in sink strength
determination. RESULTS: OsINV3 mutants showed shorter panicles with lighter and
smaller grains, owing to a smaller cell size on the outer and inner surfaces of
the palea and lemma as observed by scanning electron microscopy. Further, strong
promoter::GUS expression was observed in the palea, lemma and the rachis branches
in the young elongating panicles, which supported the role of OsINV3 in cell
expansion and thus, in spikelet size and panicle length determination. Size of
the spikelet was found to directly influence the grain weight, which was
confirmed by the lack of differences in weights of hulled grain for differently
segregated alleles in the heterozygous lines. Assessment of field grown mutants
not only revealed a drastic reduction in the percentage of ripened grain, 1000
grain weight and final yield, but also significantly reduced partitioning of
assimilates to the panicles, whereby the total dry weight remained unaffected.
Determination of the non-structural carbohydrate contents revealed a lower hexose
to-sucrose ratio in the panicles of the mutants from panicle initiation to 10
days after heading, a stage that identifies as the critical pre-storage phase of
grain filling, whereas the starch contents were not affected. In addition, strong
promoter::GUS expression was observed in the dorsal end of ovary during the pre
storage phase until 6 days after flowering, highlighting a function for OsINV3 in
monitoring the initial grain filling stage. CONCLUSIONS: OsINV3 was found to
regulate spikelet size by playing a key role in cell expansion, driving the
movement of assimilates for grain filling by modulating the hexose-to-sucrose
ratio, contributing in grain weight determination and thus, the grain yield.
PMID- 29344836
TI - Boost Irradiation Integrated to Whole Brain Radiotherapy in the Management of
Brain Metastases.
AB - Our retrospective analysis aimed to evaluate the clinical value of dose
intensification schemes: WBRT and consecutive, delayed, or simultaneous
integrated boost (SIB) in brain metastasis (BM) management. Clinical data and
overall survival (OS) of 468 patients with BM from various primaries treated with
10 * 3 Gy WBRT (n = 195), WBRT+ 10 * 2 Gy boost (n = 125), or simultaneously 15 *
2.2 Gy WBRT+0.7 Gy boost (n = 148) during a 6-year period were statistically
analysed. Significant difference in OS could be detected with additional boost to
WBRT (3.3 versus 6.5 months) and this difference was confirmed for BMs of lung
cancer and melanoma and both for oligo- and multiplex lesions. The OS was
prolonged for the RPA 2 and RPA3 categories, if patients received escalated dose,
4.0 vs. 7.7 months; (p = 0.002) in class RPA2 and 2.6 vs. 4.2 months; (p <
0.0001) in the class RPA 3 respectively. The significant difference in OS was
also achieved with SIB. The shortened overall treatment time of SIB with lower
WBRT fraction dose exhibited survival benefit over WBRT alone, and could be
applied for patients developing BM even with unfavourable prognostic factors.
These results warrant for further study of this approach with dose escalation
using the lately available solutions for hippocampus sparing and fractionated
stereotactic irradiation. The simultaneous delivery of WBRT with reduced fraction
dose and boost proved to be advantageous prolonging the OS with shortened
treatment time and reduced probability for cognitive decline development even for
patients with poor performance status and progressing extracranial disease.
PMID- 29344837
TI - Evaluation of the Profile and Mechanism of Neurotoxicity of Water-Soluble
[Cu(P)4]PF6 and [Au(P)4]PF6 (P = thp or PTA) Anticancer Complexes.
AB - [Cu(thp)4]PF6, [Cu(PTA)4]PF6, [Au(thp)4]PF6 and [Au(PTA)4]PF6 are phosphane (thp
= tris(hydroxymethyl)phosphane; PTA = 1,3,5-triaza-7-phosphaadamantane) copper(I)
and gold(I) water-soluble complexes characterized by high anticancer activity in
a wide range of solid tumors, often able to overcome drug resistance of platinum
based compounds. For these reasons, they have been proposed as a valid
alternative to platinum-based chemotherapeutic drugs (e.g., cisplatin and
oxaliplatin). In vitro experiments performed on organotypic cultures of dorsal
root ganglia (DRG) from 15-day-old rat embryos revealed that copper-based
compounds were not neurotoxic even at concentrations higher than the IC50
obtained in human cancer cells while [Au(PTA)4]PF6 was neurotoxic at lower
concentration than IC50 in cancer cell lines. The ability of these compounds to
hinder the proteasome machinery in DRG neurons was tested by fluorimetric assay
showing that the non-neurotoxic copper-based complexes do not inhibit proteasome
activity in DRG primary neuron cultures. On the contrary, the neurotoxic complex
[Au(PTA)4]PF6, induced a significant inhibition of proteasome activity even at
concentrations lower than the IC50 in cancer cells. The proteasome inhibition
induced by [Au(PTA)4]PF6 was associated with a significant increase in alpha
tubulin polymerization that was not observed following the treatment with copper
based compounds. Uptake experiments performed by atomic absorption spectrometry
showed that both copper-based complexes and [Au(PTA)4]PF6 are internalized in
neuron cultures. In vitro and in vivo preliminary data confirmed copper-based
complexes as the most promising compounds, not only for their anticancer activity
but also concerning the peripheral neurotoxicity profile.
PMID- 29344838
TI - Association between human brucellosis and adverse pregnancy outcome: a cross
sectional population-based study.
AB - To investigate the association between the incidence of human brucellosis (HB)
and adverse pregnancy outcomes (APOs), a population-based, cross-sectional
aggregate data study was conducted in Israel between 2010 and 2014. HB-endemic
localities were matched by ethnicity, population size and socioeconomic status to
localities with a low incidence of HB. We compared APO rates in high-incidence vs
low-incidence localities. The primary outcome was intrauterine fetal demise
(IUFD). Secondary outcomes were premature birth (less than 37 weeks), early or
threatened labour and poor fetal growth. APOs are expressed as events per 1,000
live or dead births. Eleven high-incidence localities, all Arab villages or
cities, were matched to 11 low-incidence localities. Localities were well-matched
with regard to the matching criteria, fertility indices, health insurance access
and education, but were imbalanced geographically. All defined APOs occurred
significantly more frequently in the high-incidence localities. The associations
translated to an absolute increase of 3.6 cases of IUFD (95% CI 1.6-5.3), 11.7
preterm births (4.8-18.3), 6.6 cases of early or threatened labour (2.2-10.9) and
7 cases of poor fetal growth (3-10.8), per 10,000 live or dead births. Owing to a
geographic imbalance between high- and low-incidence localities, we conducted an
analysis restricted to Southern localities of Arab Bedouins showing a significant
association between yearly HB incidence and IUFD incidence, odds ratio 1.05 (1.03
1.06). HB incidence is epidemiologically linked to serious pregnancy
complications. Early detection of infection through active surveillance during
pregnancy followed by appropriate treatment should be evaluated as additional
public heath strategy in endemic settings.
PMID- 29344839
TI - Risk factors of venous thrombo-embolism during cytomegalovirus infection in
immunocompetent individuals. A systematic review.
AB - Most of the effects and complications of cytomegalovirus (CMV) infection are
still unknown, even though its tropism for the endothelium has been extensively
investigated. In fact, CMV is suspected to be a cause of venous thrombo-embolism
(VTE) since 1974, but there is still no consensus about the management of CMV
related thrombosis and how to prevent it. Cytomegalovirus-related thrombosis has
been reported mostly in immunocompromised patients, rarely in immunocompetent
individuals. In order to identify potential risk factors of CMV-related
thrombosis, we performed a systematic review of the literature regarding
immunocompetent patients with cytomegalovirus infection and thrombosis. We found
115 cases with a mean age of 37.36 years (SD +/- 16.43 years). Almost half the
female patients were assuming EP contraception at the time of the event, and
almost half the patients were affected by a coagulation disorder. Interestingly,
just two women and four men had no risk factor for thrombosis other than the CMV
infection at the time of the event. In conclusion, coagulation disorders and EP
contraception have to be taken into a great deal of consideration in patients
with CMV infection, since they could be important risk factors for VTE. Knowing
the correlation with coagulation disorders, the use of anticoagulation drugs
cannot be considered overtreatment. It was not feasible to determine the
usefulness of an antiviral treatment. Further studies, even randomized ones, are
required to determine the usefulness of antiviral drugs and the real prevalence
of CMV-related VTE.
PMID- 29344840
TI - Design and Rationale for comParison Between ticagreLor and clopidogrEl on
mIcrocirculation in Patients with Acute cOronary Syndrome Undergoing Percutaneous
Coronary Intervention (PLEIO) Trial.
AB - It has been previously demonstrated that ticagrelor can reduce mortality compared
to clopidogrel in acute coronary syndrome (ACS) patients. However, the mechanism
for this mortality reduction remains uncertain. The objective of the present
study is to assess the impact of chronic ticagrelor treatment on microvascular
circulation. A total of 120 participants aged 20-85 years with clinical diagnosis
of ACS will be randomized in a 1:1 fashion to the following two groups:
ticagrelor 90 mg twice daily; clopidogrel 75 mg once daily. To evaluate the
status of microcirculation, the primary end point is coronary microvascular
dysfunction measured using an index of microcirculatory resistance (IMR) at 6
months after receiving the study agent. The purpose of this trial is to
investigate whether ticagrelor, beyond its antiplatelet efficacy, could improve
coronary microcirculation more effectively than clopidogrel for patients with
ACS.
PMID- 29344841
TI - Association of D-dimer with Plaque Characteristics and Plasma Biomarkers of
Oxidation-Specific Epitopes in Stable Subjects with Coronary Artery Disease.
AB - D-dimer has emerged as a biomarker of cardiovascular event risk, yet
pathophysiological factors associated with plasma D-dimer levels in stable
coronary artery disease (CAD) subjects are poorly understood. In 106 stable CAD
subjects undergoing intravascular ultrasound with virtual histology (IVUS-VH), we
measured D-dimer, lipoprotein(a) (Lp(a)), plasminogen, biomarkers reflecting
oxidation-specific epitopes (OSE) such as oxidized phospholipids on
apolipoprotein B-100 (OxPL-apoB), OxPL on plasminogen (OxPL-PLG), and
autoantibodies to phosphorylcholine-BSA [PC-BSA] and a malondialdehyde [MDA]
mimotope. In univariate analysis, D-dimer was positively associated with Lp(a),
OxPL-apoB, OxPL-PLG, and coronary artery calcium, and inversely associated with
autoantibodies to OSE and plaque fibrosis. D-dimer levels > 500 ng/ml also showed
positive association with plaque necrosis. After multivariate analysis, D-dimer
remained significantly associated with Lp(a) and plaque calcium. While further
studies are needed, results provide evidence that plasma D-dimer levels are
associated with levels of OxPLs and IVUS-VH indices linked to plaque erosion and
rupture.
PMID- 29344842
TI - Reasons for Abortion: Religion, Religiosity/Spirituality and Attitudes of Male
Secondary School Youth in South Africa.
AB - This study focused on the relationship between religion, religiosity/spirituality
(R/S), and attitudes of a sample of South African male secondary school youth
toward women's rights to legal abortion in different situations. We distributed
400 self-administered questionnaires assessing the main variables (attitudes
toward reasons for abortion and R/S) to the target sample in six different
secondary schools in KwaZulu-Natal, South Africa. The responses of a final sample
of 327 learners were then analyzed using the Statistical Package for the Social
Sciences (SPSS) software. The findings revealed that religion and R/S play a role
in the youths' attitudes toward abortion. While the Hindu subsample indicated
higher overall support across the different scenarios, the Muslim subsample
reported greater disapproval than the other groups on 'Elective reasons' and in
instances of 'Objection by significant others.' The Christian youth had the most
negative attitudes to abortion for 'Traumatic reasons' and 'When women's
health/life' was threatened. Across the sample, higher R/S levels were linked
with more negative attitudes toward reasons for abortion.
PMID- 29344843
TI - Hepatocellular Carcinoma Spreading Through the Round Ligament.
PMID- 29344844
TI - Response to: "The Role of Bundle Size for Preventing Surgical Site Infections
after Colorectal Surgery: Is More Better?"
PMID- 29344845
TI - Two Cases of Dermatophytic Granuloma Successfully Treated with Terbinafine.
AB - Dermatophytic granuloma, also called Majocchi's granuloma (MG), is an uncommon
infection of the dermis and subcutaneous tissues that can occur in both healthy
and immunosuppressed hosts. We present two cases of MG with different clinical
features. Both patients had satisfactory relief after treatment with terbinafine.
PMID- 29344846
TI - Evaluation of psychosocial and biological parameters in women seeking for a
caesarean section and women who are aiming for vaginal delivery: a cross
sectional study.
AB - PURPOSE: To investigate psychosocial and biological parameters that may influence
decision-making concerning the mode of delivery in women with caesarean section
on maternal request (CSMR). METHODS: Two hundred and two women were enrolled
prospectively. The study sample (n = 93) consisted of women who aimed for CSMR,
the control sample were women who seeked for vaginal delivery (n = 109).
Parturients of both samples were enrolled during the pre-birth counselling at the
delivery room at the University Medical Centre Mannheim, University Heidelberg,
Germany. Women completed standardised questionnaires regarding psychosocial
burden (SCL-R 90), fear of childbirth (W-DEQ) and anxiety (STAI), personality
structure (HEXACO-Pi-R), and ambiguity tolerance (PFI, PNS, and NFC), social
support (F-SozU) as well as one questionnaire assessing demographic parameters
and further factors potentially influencing their choice of the mode of delivery.
Hair cortisol concentration as a marker for chronic psychological stress and
pressure pain threshold with a pressure algometer was assessed. RESULTS: Women in
the CSMR sample had less social support (F-SozU: 2.99 +/- 0.52 vs. 3.12 +/- 0.32;
p = 0.043) and were less educated (high school or university degree: 37 vs. 71%,
p = 0.001) compared to parturients of the control sample. Women who underwent
CSMR were less open-minded (HEXACO-Pi-R: 3.08 +/- 0.57 vs. 3.26 +/- 0.50; p =
0.016) and less extroverted (HEXACO-Pi-R: 3.34 +/- 0.36 vs. 3.46 +/- 0.41; p =
0.041). The control collective showed higher scores in negative appraisal of the
birth ('W-DEQ-negative appraisal': 2.5 +/- 0.8 vs. 2.2 +/- 0.9; p = 0.006),
whereas "lack of positive anticipation" was higher in the study collective ('W
DEQ-lack of positive anticipation': 3.2 +/- 1.2 vs. 2.8 +/- 0.8; p = 0.015). The
study collective had higher pressure pain threshold values (5.07 +/- 2.06 vs.
4.35 +/- 1.38; p = 0.007), while no significant differences were observed in hair
cortisol concentration comparing both groups (5.0 +/- 11.4 vs. 4.9 +/- 8.3; p =
0.426). The majority of the control collective (80%) had chosen the vaginal route
as their mode of delivery before pregnancy, whereas only 21% of the women in the
study collective decided to undergo CSMR before conception. The advice of social
sources including both medical and non-medical aspects was rated less important
in the study sample, with significant differences indicating a lower relevance of
counsel from friends (p = 0.002) and midwives (p < 0.001). CONCLUSION: Women who
inquired a CSMR had lower social support, were less educated, more anxious, and
had a lower sensitivity for physical pain compared to women seeking for
spontaneous delivery. This should be considered when counselling women requiring
CSMR and could be leverage points to intervene to reduce the continuously
increasing CSMR rate.
PMID- 29344848
TI - Current status and future possibilities of molecular genetics techniques in
Brassica napus.
AB - As PCR methods have improved over the last 15 years, there has been an upsurge in
the number of new DNA marker tools, which has allowed the generation of high
density molecular maps for all the key Brassica crop types. Biotechnology and
molecular plant breeding have emerged as a significant tool for molecular
understanding that led to a significant crop improvement in the Brassica napus
species. Brassica napus possess a very complicated polyploidy-based genomics. The
quantitative trait locus (QTL) is not sufficient to develop effective markers for
trait introgression. In the coming years, the molecular marker techniques will be
more effective to determine the whole genome impairing desired traits. Available
genetic markers using the single-nucleotide sequence (SNP) technique and high
throughput sequencing are effective in determining the maps and genome
polymorphisms amongst candidate genes and allele interactions. High-throughput
sequencing and gene mapping techniques are involved in discovering new alleles
and gene pairs, serving as a bridge between the gene map and genome evaluation.
The decreasing cost for DNA sequencing will help in discovering full genome
sequences with less resources and time. This review describes (1) the current use
of integrated approaches, such as molecular marker technologies, to determine
genome arrangements and interspecific outcomes combined with cost-effective
genomes to increase the efficiency in prognostic breeding efforts. (2) It also
focused on functional genomics, proteomics and field-based breeding practices to
achieve insight into the genetics underlying both simple and complex traits in
canola.
PMID- 29344847
TI - The effect of surgical management of endometrioma on the IVF/ICSI outcomes when
compared with no treatment? A systematic review and meta-analysis.
AB - OBJECTIVE: To assess the impact of surgical management of endometrioma on the
outcome of assisted reproduction treatment (ART). DESIGN: A systematic review and
meta-analysis. SETTING: Department of reproductive medicine at teaching
university hospital, UK. PATIENTS: Subfertile women with endometrioma undergoing
ART. INTERVENTIONS: Surgical removal of endometrioma or expectant management.
MAIN OUTCOME MEASURES: Clinical pregnancy rate, pregnancy rate, live birth rate,
number of oocytes retrieved and number of embryos available and ovarian response
to gonadotrophins. RESULTS: An extensive search of electronic databases for
articles published from inception to September 2016 yielded 11 eligible studies
for meta-analysis. Meta-analysis was conducted comparing surgery versus no
treatment of endometrioma. There were no significant differences in pregnancy
rate per cycle, clinical pregnancy rate and live birth rate between women who
underwent surgery for endometrioma and those who did not. CONCLUSION: Current
evidence suggests that women with endometriosis-related infertility have similar
cycle outcomes to other patients going through ART. It is pertinent for
clinicians to assess the risks of surgical intervention on ovarian reserve prior
to initiating therapy.
PMID- 29344849
TI - A simple protocol for transfecting human mesenchymal stem cells.
AB - OBJECTIVES AND RESULTS: Mesenchymal stromal cells (MSCs) are potential targets
for cell and gene therapy-based approaches against a variety of different
diseases. The MSCs from bone marrow are a promising target population as they are
capable of differentiating along multiple lineages and have significant expansion
capability. These characteristics make them strong candidates for delivering
genes and restoring organ systems function. However, as other primary cells, MSCs
are difficult to transfect. In order to standardize a simple protocol for
transfection of MSCs, we conducted a series of experiments and achieved a
protocol that does not require the use of viral particles or specific expensive
equipment. CONCLUSION: MSCs transfection at early passages using a ratio
lipid/DNA of 3.0 uL/ug with Lipofectamine 3000(r) yields good transfection
efficiencies for human MSCs (up to 26%) and is rapid, simple, and safe.
PMID- 29344850
TI - HuR facilitates cancer stemness of lung cancer cells via regulating miR-873/CDK3
and miR-125a-3p/CDK3 axis.
AB - OBJECTIVES: To study the roles and mechanisms of HuR in cancer stem cell
maintenance of lung cancer. RESULTS: HuR expression was increased in tumor
spheres of lung cancer cells. Knockdown of HuR suppressed spheroid formation and
size, inhibited the expression of stemness-related marker, Oct4, Nanog and ALDH
in lung cancer cells. Importantly, HuR and CDK3 expressions were increased in
lung cancer tissues compared with normal adjacent tissues, and positively
correlated. Mechanistically, HuR directly bound to CDK3, and increased CDK3 mRNA
stability and expression. Additionally, miR-873 or miR-125a-3p attenuated the
promotion of HuR on CDK3 expression and lung cancer stemness. Furthermore, HuR
facilitated lung cancer stemness dependent on CDK3 expression. miR-873 or miR
125a-3p level was negatively correlated with HuR and CDK3 expression levels in
lung cancer tissues. CONCLUSIONS: HuR facilitates lung cancer stemness via
regulating miR-873/CDK3 and miR-125a-3p/CDK3 axis.
PMID- 29344851
TI - The evolution of CRISPR/Cas9 and their cousins: hope or hype?
AB - Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system
allows biologists to edit genomic DNA of any cell in precise and specific way,
entailing great potential for crop improvement, drug development and gene
therapy. The system involves a nuclease (Cas9) and a designed guide RNA that are
involved in wide range of applications such as genome modification,
transcriptional modulation, genomic loci marking and RNA tracking. The limitation
of the technique, in view of resistance of thymidine-rich genome to Cas9
cleavage, has now been overcome by the use of Cpf1 nuclease. In this review, we
present an overview of CRISPR nucleases (Cas9 or Cpf1) with particular emphasis
on human genome modification and compare their advantages and limitations.
Furthermore, we summarize some of the pros and cons of CRISPR technology
particularly in human therapeutics.
PMID- 29344852
TI - Laser Capture Microdissection: Insights into Methods and Applications.
AB - Laser capture microdissection is a non-molecular, minimally disruptive method to
obtain cytologically and/or phenotypically defined cells or groups of cells from
heterogeneous tissues. Its advantages include efficient rapid and precise
procurement of cells. The potential disadvantages include time consuming,
expensive, and limited by the need for a pathologist for recognition of distinct
subpopulations within a specified sample. Overall it is versatile allowing the
preparation of homogenous isolates of specific subpopulations of cells from which
DNA/RNA or protein can be extracted for RT-PCR, quantitative PCR, next-generation
sequencing, immunoblot blot analyses, and mass spectrometry.
PMID- 29344853
TI - Laser Microdissection-Based Microproteomics of Formalin-Fixed and Paraffin
Embedded (FFPE) Tissues.
AB - Laser microdissection-based proteomics on formalin-fixed and paraffin-embedded
tissues is usually performed from relatively large tissue areas or pools of
multiple tissue pieces. However, several molecular pathology studies require
working on very limited amounts of tissue. This is for example the case when very
early cancer lesions have to be handled. Hereby, we present a method for the
processing of very small pieces of formalin-fixed and paraffin-embedded tissues
for proteomic purposes. This approach is designed in order to avoid sample loss
during technical processing and to optimize the digestion of tissue areas
containing as little as 2700 cells.
PMID- 29344854
TI - Laser Microdissection Workflow for Isolating Nucleic Acids from Fixed and Frozen
Tissue Samples.
AB - Laser Capture Microdissection has earned a permanent place among modern
techniques connecting histology and molecular biology. Laser Capture
Microdissection has become an invaluable tool in medical research as a means for
collection of specific cell populations isolated from their environment. Such
genomic sample enrichment dramatically increases the sensitivity and precision of
downstream molecular assays used for biomarker discovery, monitoring disease
onset and progression, and in the development of personalized medicine. The
diversity of research targets (cancerous and precancerous lesions in clinical and
animal research, cell pellets, rodent embryos, frozen tissues, archival
repository slides, etc.) and scientific objectives present a challenge in
establishing standard protocols for Laser Capture Microdissection. In the present
chapter, we share our experiences in design and successful execution of numerous
diverse microdissection projects, and provide considerations to be taken into
account in planning a microdissection study. Our workflow and protocols are
standardized for a wide range of animal and human tissues and adapted to
downstream analysis platforms.
PMID- 29344855
TI - Protocol for the Analysis of Laser Capture Microdissected Fresh-Frozen Tissue
Homogenates by Silver-Stained 1D SDS-PAGE.
AB - The heterogeneity present in solid tumors adds significant difficulty to
scientific analysis and improved understanding. Fundamentally, solid tumor
formation consists of cancer cells proper along with stromal elements. The
burgeoning malignant process is dependent upon modified stromal elements.
Collectively, the stroma forms an essential microenvironment, which is
indispensable for the survival and growth of the malignant neoplasm. This
cellular heterogeneity makes molecular profiling of solid tumors via mass
spectrometry (MS)-based proteomics a daunting task. Laser capture microdissection
(LCM) is commonly used to obtain distinct histological cell types (e.g., tumor
parenchymal cells, stromal cells) from tumor tissue and attempt to address the
tumor heterogeneity interference with downstream liquid chromatography (LC) MS
analysis. To provide optimal LC-MS analysis of micro-scale and/or nano-scale
tissue sections, we modified and optimized a silver-stained one-dimensional
sodium dodecyl sulfate polyacrylamide gel electrophoresis (1D-SDS-PAGE) protocol
for the LC-MS analysis of LCM-procured fresh-frozen tissue specimens. Presented
is a detailed in-gel digestion protocol adjusted specifically to maximize the
proteome coverage of amount-limited LCM samples, and facilitate in-depth
molecular profiling. Following LCM, targeted tissue sections are further
fractionated using silver-stained 1D-SDS-PAGE to resolve and visualize tissue
proteins prior to in-gel digestion and subsequent LC-MS analysis.
PMID- 29344856
TI - Next-Generation Sequencing Analysis of Laser-Microdissected Formalin-Fixed and
Paraffin-Embedded (FFPE) Tissue Specimens.
AB - In recent years, next-generation sequencing (NGS) became widely used in molecular
pathology. Comprehensive mutational profiling improved diagnosis and prognosis,
as well as the identification of therapeutically relevant genetic alterations.
However, the vast majority of studies analyzing tissue samples use DNA extracted
from bulk tissue or only manually microdissected specimens. Laser-assisted
microdissection offers the possibility of isolating morphologically defined small
tissue compartments (like individual glands) or even of single cells for further
molecular analysis. Even formalin-fixed paraffin-embedded (FFPE) tissue specimens
can be used for laser-assisted microdissection. Combining these two innovative
powerful methodological approaches provides invaluable insights into the genetic
profile of any cell type and tissue compartment of interest, contributing to a
better understanding of fundamental biological processes and disease-specific
mechanisms.In this chapter, a detailed protocol is provided for microdissection
of human mammary adenomyoepithelioma tissue specimens and subsequent targeted
resequencing of a panel of cancer-related genes using IonTorrent/PGM technology.
PMID- 29344857
TI - Adaptation of Laser Microdissection Technique to Nanostring RNA Analysis in the
Study of a Spontaneous Metastatic Mammary Carcinoma Mouse Model.
AB - The mouse model characterized by spontaneous lung metastasis from JygMC (A) cells
closely resembles the human triple negative breast cancer (TNBC) subtype. The
primary tumors morphologically present both epithelial and spindle-like cells,
but metastases in lung parenchyma display only adenocarcinoma properties. In the
study of molecular signatures, laser capture microdissection (LCM) on frozen
tissue sections was used to separate the following regions of interest: the
epithelial-mesenchymal transition (EMT), mesenchymal-epithelial transition (MET),
carcinoma, lung metastases, normal mammary gland and normal lung parenchyma.
NanoString was selected for the study of molecular signatures in LCM targets as a
reliable downstream gene expression platform allowing analysis of tissue lysates
without RNA extraction and amplification. This chapter provides detailed
protocols for the collection of tissue, LCM sample preparation and dissection,
production of lysates, extraction, and quality control of RNA for NanoString
analysis, as well as the methodology of Nanostring gene expression profiling
experiment.
PMID- 29344858
TI - Laser Capture Microdissection as a Tool to Study the Mucosal Immune Response in
Celiac Disease.
AB - Laser capture microdissection (LCM) is a powerful tool for selection and
isolation of single cells or compartments from complex primary tissues to perform
molecular analyses. Celiac disease is a genetic autoimmune disorder where the
ingestion of gluten leads to damage in the small intestine. Increased
intraepithelial lymphocytes and the presence of the lamina propria inflammatory
infiltrate of the duodenal mucosa is a common part of the disease. These cells
promote inflammatory processes through the release of cytokines. Here, we
describe the use of LCM and real-time quantitative PCR (RT-qPCR) to analyze
cytokine profile information in distinct duodenal mucosa tissue compartments of
celiac patients.
PMID- 29344859
TI - Laser Capture Microdissection and Isolation of High-Quality RNA from Frozen
Endometrial Tissue.
AB - Laser capture microdissection (LCM) allows expression profiling of specific cell
populations within tissues. However, isolation of high-quality RNA from laser
capture microdissected frozen tissue is beset by problems arising from intrinsic
tissue RNase activity. Herein, we describe an optimized staining/LCM/RNA
extraction protocol developed for the isolation of epithelial RNA from frozen
tissue sections using human endometrial cancer as a model tissue. This method
combines excellent, reproducible visualization of tissue morphology with the
isolation of high-integrity RNA suitable for downstream applications such as
expression microarray analysis. We present quantitative and qualitative RNA data
obtained from >200 endometrial epithelial samples (normal, hyperplastic, and
cancerous), where 92% of samples had RIN values of 7 and above and highlight
common pitfalls faced by investigators. This method should also be broadly
applicable to a range of other tissue types.
PMID- 29344860
TI - Laser Microdissection for Human Papillomavirus (HPV) Genotyping Attribution and
Methylation Pattern Analyses of Squamous Intraepithelial Lesions.
AB - Human papillomavirus (HPV) is a nearly ubiquitous infectious organism. It is
estimated that 80% of sexually active adults will be exposed to anogenital HPVs
in their lifetime, and detection of multiple genotypes in an anogenital sample is
common. Detection and genotyping of HPV is usually performed by DNA testing, and
less frequently by mRNA testing. HPV genotype testing and characterization of DNA
methylation patterns of HPV-related lesions can provide important biological,
epidemiological, and potentially relevant clinical information in individuals and
populations. The use of laser capture microdissection to isolate cells within a
specific lesion allows for very precise molecular characterization and hence
causal attribution. This chapter describes detailed protocols for the capture of
lesion-specific tissue from formalin-fixed, paraffin-embedded (FFPE) biopsy
tissue, and downstream DNA testing for lesion-specific HPV genotype and their
methylation patterns.
PMID- 29344861
TI - Laser Capture Microdissection and Transcriptional Analysis of Sub-Populations of
the Osteoblast Lineage from Undecalcified Bone.
AB - Transcriptional analysis of tissue samples is a useful and widely applied
approach to provide insight into the molecular mechanisms engaged in response to
phenotypic changes or external stimuli. We describe a method that overcomes the
technical challenges associated with the application of Laser Capture
Microdissection to undecalcified bone enabling us to collect high-quality bone
tissue with maintained cellular morphology that is suitable for cryosectioning,
fixation, and cutting. Using this method, we obtain samples enriched for specific
cell types from the mature osteoblast lineage (osteoblasts, lining cells, i.e.,
quiescent osteoblasts, and osteocytes). RNA is well preserved and following
extraction and amplification can be used as input to both low and high-throughput
RNA analysis formats.
PMID- 29344862
TI - Cell Type-Specific Laser Capture Microdissection for Gene Expression Profiling in
the Human Brain.
AB - Cell type-specific laser microdissection technologies in combination with
molecular techniques to determine gene expression profiles have become powerful
tools to gain insight into the neurobiological basis of neural circuit
disturbances in various neurologic or psychiatric diseases. To identify specific
cell populations in human postmortem brain tissue, one can use the inherent
properties of the cells, such as pigmentation and morphology or their structural
composition through immunohistochemistry (IHC). Here, we describe the isolation
of homogeneous neurons and oligodendrocytes and the extraction of high-quality
RNA from these cells in human postmortem brain using a combination of rapid IHC,
Nissl staining, or simple morphology with Laser Capture Microdissection (LCM), or
Laser Microdissection (LMD).
PMID- 29344863
TI - The Isolation of Pure Populations of Neurons by Laser Capture Microdissection:
Methods and Application in Neuroscience.
AB - In mammals, the central nervous system (CNS) is constituted of various cellular
elements, posing a challenge to isolating specific cell types to investigate
their expression profile. As a result, tissue homogenization is not amenable to
analyses of motor neurons profiling as these represent less than 10% of the total
spinal cord cell population. One way to tackle the problem of tissue
heterogeneity and obtain meaningful genomic, proteomic, and transcriptomic
profiling is to use laser capture microdissection technology (LCM). In this
chapter, we describe protocols for the capture of isolated populations of motor
neurons from spinal cord tissue sections and for downstream transcriptomic
analysis of motor neurons with RT-PCR. We have also included a protocol for the
immunological confirmation that the captured neurons are indeed motor neurons.
Although focused on spinal cord motor neurons, these protocols can be easily
optimized for the isolation of any CNS neurons.
PMID- 29344864
TI - Laser Capture Microdissection in Traumatic Brain Injury Research: Obtaining
Hippocampal Subregions and Pools of Injured Neurons for Genomic Analyses.
AB - The methods presented here are based on our laboratory's 15 years of experience
using laser capture microdissection to obtain samples for the study of gene
expression after traumatic brain injury (TBI) using a well-established rat model
of experimental TBI. Here, we describe how to use the ArcturusXT laser capture
microdissection system to capture swaths of specific regions of the rat
hippocampus as well as specific neuronal populations defined by Fluoro-Jade C
staining. Staining with Fluoro-Jade C identifies a neuron that is in the process
of degeneration. We have optimized our protocols for Fluoro-Jade C tissue
staining and laser capture microdissection to maintain RNA integrity which is
essential for a variety of downstream applications, such as microarray, PCR
array, and quantitative real-time PCR analyses.
PMID- 29344865
TI - Isolation of Distinct Types of Neurons from Fresh Brain Tissue Using Laser
Microdissection in Combination with High-Performance Liquid Chromatography-Mass
Spectrometry.
AB - Humans age and the ageing process affects cells in all areas of the human body,
including nerve cells within the brain. With advancing age there is also a rise
in the probability of developing a neurodegenerative disorder such as, e.g.,
amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, or
Alzheimer's disease. In all these age-related neurodegenerative disorders,
distinct neuron populations within specific brain regions are primarily affected.
For example, Parkinson's disease is characterized by a slowly progressive
degeneration of dopaminergic neurons in the substantia nigra whereas the
entorhinal cortex is first affected in Alzheimer's disease. In patients suffering
from Huntington's disease, neurons in both striatum and cortex undergo
substantial cell loss and in amyotrophic lateral sclerosis the neurodegeneration
arises from the spinal cord and the motor cortex. For the investigation of the
differences in neuronal vulnerability, it is important to examine the protein
expression pattern in these specific neural populations. By this, conclusions
about the origination process of these diseases can be achieved. In order to
obtain this objective, specific isolation of distinct neurons from the
surrounding brain tissue is indispensable. However, discrimination as well as
isolation of distinct types of neurons can be challenging, due to the brain
tissue's complexity. With traditional methods such as the homogenization of
tissue samples, a specific isolation of single neuron populations is not feasible
because homogenization results into a mixture containing all cell types. Laser
microdissection can overcome this technical limitation. First, this method
enables visualization of tissues via a microscopic unit and therefore an enhanced
discrimination of different brain cells. Second, a laser device guarantees a
contact-free and consequently a contamination-free separation of distinct neurons
from the surrounding brain tissue. In the following, we present a detailed
protocol that includes a workflow for the isolation and analysis of neurons from
freshly frozen post mortem human brain tissue samples. During this procedure, the
brain tissue is sectioned, stained, laser microdissected, and ultimately analyzed
by high-performance liquid chromatography-mass spectrometry.
PMID- 29344866
TI - Immuno-Guided Laser-Capture Microdissection of Glial Cells for mRNA Analysis.
AB - Laser-capture microdissection (LCM) allows for retrieval of specific cell
populations in situ. By combining immunofluorescent labeling with LCM, mRNAs can
be probed by qRT-PCR for determining in situ gene expression during health and
disease. This approach permits obtaining and analyzing histologically enriched
cell populations in a tissue that can be hardly obtained from other methods such
as white matter astrocytes from rodents or any individual cell population from
archival human or rodent brain tissues. Herein, we present our methodology of
laser-captured mouse spinal cord white matter astrocytes, which can be adapted
for any cell type in CNS tissue and low RNAse containing tissues. The methods
presented with an emphasis on tips and advices include the cryostat section
preparation from snap-frozen tissue, an adapted immunofluorescent labeling, a
brief overview of LCM using a UV-based technology with polyethylene membrane
glass slides, procedures for direct use of RNA from lysis buffer vs. column-based
purified RNA, RNA quality/quantity assessment, the reverse transcription and
preamplification steps used before real-time qPCR analysis.
PMID- 29344867
TI - Immuno-Laser-Capture Microdissection for the Isolation of Enriched Glial
Populations from Frozen Post-Mortem Human Brain.
AB - Laser-capture microdissection (LCM) has revolutionized the isolation of defined
regions and specific cell populations from human tissue. This approach used in
combination with immunohistochemistry (immuno-LCM) has become a valuable method
for isolating individual cell-types from a complex heterogeneous population.
Here, we describe the detailed methodology required for the isolation of enriched
populations of GFAP+ astrocytes, OSP+ oligodendrocytes, and CD68+ microglia from
frozen post-mortem human central nervous system tissue using immuno-LCM.
PMID- 29344868
TI - Laser-Capture Microdissection for the Analysis of Rat and Human Spinal Cord
Ependyma by qPCR.
AB - In the last few decades many efforts have been dedicated to decipher the nature
and regenerative potential of neurogenic niches and endogenous stem cells after
damage of the central nervous system. In the spinal cord, it has been largely
focused on the ependymal region, which hosts neural precursors/stem cells (NSC)
in rodents but differs between species and ages. In the current chapter, we
detail our protocol to study the gene expression profile of this region using
fresh frozen blocks of rat and human post-mortem spinal cords. We describe how to
prepare and process those tissues, how to identify and dissect the ependymal
region using Laser-Capture Microdissection (LCMD), and how to isolate and amplify
RNA with different integrity states to finally obtain enough material for
performing gene expression assays using Taqman(r) Low Density Arrays. LCMD
technique maintains tissue integrity allowing for subsequent analysis without
manipulation steps that may alter molecular properties of cells and the eventual
loss of delicate cell types in comparison with other approaches that require
previous disaggregation of the tissue and cell manipulation before isolation.
PMID- 29344869
TI - Isolation of Amyloid Plaques and Neurofibrillary Tangles from Archived
Alzheimer's Disease Tissue Using Laser-Capture Microdissection for Downstream
Proteomics.
AB - Here, we describe a new method that allows localized proteomics of amyloid
plaques and neurofibrillary tangles (NFTs), which are the two pathological
hallmarks of Alzheimer's disease (AD). Amyloid plaques and NFTs are visualized
using immunohistochemistry and microdissected from archived, formalin-fixed
paraffin-embedded (FFPE) human tissue samples using laser-capture
microdissection. The majority of human tissue specimens are FFPE; hence the use
of this type of tissue is a particular advantage of this technique.
Microdissected tissue samples are solubilized with formic acid and
deparaffinized, reduced, alkylated, proteolytically digested, and desalted. The
resulting protein content of plaques and NFTs is determined using label-free
quantitative LC-MS. This results in the unbiased and simultaneous quantification
of ~900 proteins in plaques and ~500 proteins in NFTs. This approach permits
downstream pathway and network analysis, hence providing a comprehensive overview
of pathological protein accumulation found in neuropathological features in AD.
PMID- 29344870
TI - Cell-Specific RNA Quantification in Human SN DA Neurons from Heterogeneous Post
mortem Midbrain Samples by UV-Laser Microdissection and RT-qPCR.
AB - Cell specificity of gene expression analysis is from particular relevance when
the abundance of target cells is not homogeneous in the compared tissue samples,
like it is the case, e.g., when comparing brain tissues from controls and in
neurodegenerative disease states. While single-cell gene expression profiling is
already a methodological challenge per se, it becomes even more prone to
artifacts when analyzing individual cells from human post-mortem samples. Not
only because human samples can never be matched as precisely as those from animal
models, but also, because the RNA-quality that can be obtained from human samples
usually displays a high range of variability. Here, we detail our most actual
method for combining contact-free UV-laser microdissection (UV-LMD) with reverse
transcription and quantitative PCR (RT-qPCR) that addresses all these issues. We
specifically optimized our protocols to quantify and compare mRNA as well as
miRNA levels in human neurons from post-mortem brain tissue. As human post-mortem
tissue samples are never perfectly matched (e.g., in respect to distinct donor
ages and RNA integrity numbers RIN), we refined data analysis by applying a
linear mixed effects model to RT-qPCR data, which allows dissecting and
subtracting linear contributions of distinct confounders on detected gene
expression levels (i.e., RIN, age). All these issues were considered for
comparative gene expression analysis in dopamine (DA) midbrain neurons of the
Substantia nigra (SN) from controls and Parkinson's disease (PD) specimens, as
the preferential degeneration of SN DA neurons in the pathological hallmark of
PD. By utilizing the here-described protocol we identified that a variety of
genes-encoding for ion channels, dopamine metabolism proteins, and PARK gene
products-display a transcriptional dysregulation in remaining human SN DA neurons
from PD brains compared to those of controls. We show that the linear mixed
effects model allows further stratification of RT-qPCR data, as it indicated that
differential gene expression of some genes was rather correlated with different
ages of the analyzed human brain samples than with the disease state.
PMID- 29344871
TI - Laser-Capture Microdissection for Layer-Specific Analysis of Enteric Ganglia.
AB - The enteric nervous system (ENS) is the division of the autonomic nervous system
that innervates the gastrointestinal (GI) tract and controls central intestinal
functions such as peristalsis and fluid movement. Enteric nerve cell bodies
(neurons and glia) are predominantly organized in ganglionated networks that are
present along the entire length of the GI tract in multiple tissue layers. Most
cell bodies are organized in the myenteric plexus allocated between the
longitudinal and the circular muscle layers or in the submucosal plexus between
muscle tissue and mucosa. The site-specific characteristics of these enteric
nerve cells have traditionally been analyzed via imaging techniques. Laser
capture microdissection (LCM) offers the prospect of site-specifically analyzing
the gene expression profiles of these different subpopulations. This protocol
addresses critical aspects of handling intestinal tissue for ENS dissection, such
as the optimal quick-staining procedure, suitable laser settings, and limits of
tissue material required to successfully dissect and analyze tissue layers for
gene expression.
PMID- 29344872
TI - A Laser Microdissection-Liquid Chromatography-Tandem Mass Spectrometry Workflow
for Post-mortem Analysis of Brain Tissue.
AB - Improved speed and sensitivity of mass spectrometry allow the simultaneous
quantification of high numbers of proteins from increasingly smaller quantities
of tissue sample. Quantitative data of the proteome is highly valuable for
providing unbiased information on, for example, protein expression changes
related to disease or identifying related biomarkers. In brain diseases the
affected area can be small and pathogenic events can be related to a specific
cell type in an otherwise heterogeneous tissue type. An emerging approach
dedicated to analyzing this type of samples is laser micro-dissection (LMD)
combined with LC-MS/MS into a single workflow. In this chapter, we describe
different options for isolating tissue suitable for LC-MS/MS analysis.
PMID- 29344873
TI - Laser-Capture Microdissection and RNA Extraction from Perfusion-Fixed Cartilage
and Bone Tissue from Mice Implanted with Human iPSC-Derived MSCs in a Calvarial
Defect Model.
AB - Laser-capture microdissection (LCM) coupled to downstream RNA analysis poses
unique difficulties for the evaluation of mineralized tissues. A rapid protocol
was thus developed to enable sufficient integrity of bone and cartilage tissue
for reliable sectioning, while minimizing RNA loss associated with prolonged
decalcification and purification steps. Specifically, the protocol involves pump
assisted, cardiac perfusion-fixation with paraformaldehyde, and moderate
digestion of LCM-acquired tissue with proteinase K followed by DNase treatment
and separation of RNA using magnetic beads. Reverse transcription and cDNA
synthesis are performed immediately after RNA purification, without need for
further protein removal.
PMID- 29344874
TI - Laser Capture Microdissection-Based RNA-Seq of Barley Grain Tissues.
AB - Spatiotemporal patterning throughout the plant body depends to a large degree on
cell- and tissue-specific expression of genes. Subsequently, for a better
understanding of cell and tissue differentiation processes during plant
development it is important to conduct transcript analyses in individual cells or
tissue types rather than in bulk tissues. Laser capture microdissection (LCM)
provides a useful method for isolating specific cell types from complex tissue
structures for downstream applications. Contrasting to mammalian cells, the
texture of plant cells is more critical due to hard, cellulose-rich cell walls,
large vacuoles, and air spaces which complicates tissue preparation and
extraction of macromolecules, like DNA and RNA. In particular, developing barley
seeds (i.e. grains) depict cell types with differences in osmomolarity
(meristematic, differentiating and degenerating tissues) and contain high amounts
of the main storage product starch. In this study, we report about methods
allowing tissue-specific transcriptome profiling by RNA-seq of developing barley
grain tissues from low-input RNA amounts. Details on tissue preparation, laser
capture microdissection, RNA isolation, and linear mRNA amplification to produce
high-quality samples for Illumina sequencing are provided. Particular emphasis
was placed on the influence of the mRNA amplification step on the transcriptome
data and the fidelity of deduced expression levels obtained by the developed
methods. Analysis of RNA-seq data confirmed sample processing as a highly
reliable and reproducible procedure that was also used for transcriptome analyses
of different tissue types from barley plants.
PMID- 29344875
TI - Development of a Prognostic Prediction Model to Determine Severe Dengue in
Children.
AB - OBJECTIVE: To develop a prognostic prediction model using the seven warning signs
highlighted by WHO revised Dengue fever classification 2009 to determine severe
dengue in children. METHODS: In this prospective analytical study conducted in a
tertiary care centre, consecutive sampling of all children aged 1mo to 12y
admitted with serologically confirmed Dengue was done from May 2015 through
August 2016. After excluding 27 patients with co-infections and co-morbidities,
359 patients were followed up daily to assess clinical and laboratory progression
till discharge/ death. Independent predictors were abdominal pain or tenderness,
persistent vomiting, lethargy, mucosal bleed, clinical fluid accumulation,
hepatomegaly >2 cm and rising hematocrit concurrent with platelet count <100 *
109/L. Outcome measure was severe dengue defined as per WHO guidelines 2009.
RESULTS: Among 359 children, 93 progressed to severe dengue. In univariate
analysis, significant predictors were clinical fluid accumulation (OR 4.773, p =
0.000, 95%CI 2.511-9.075), persistent vomiting (OR 1.944, p = 0.010, 95%CI 1.170
3.225), mucosal bleed (OR 2.045, p = 0.019, 95%CI 1.127-3.711) and hematocrit
>=0.40 concurrent with platelet count <100 * 109/L (OR 2.985, p = 0.000, 95%CI
1.783-4.997). The final multivariable model included clinical fluid accumulation
(aOR 3.717, p = 0.000, 95%CI 1.901-7.269), hematocrit >=0.40 concurrent with
platelet count <100 * 109/L (aOR 2.252, p = 0.004, 95%CI 1.302-3.894) and
persistent vomiting (p = 0.056) as predictors of severe dengue. CONCLUSIONS:
Among seven WHO warning signs, predictors of severe dengue as suggested by the
present multivariable prediction model include clinical fluid accumulation,
persistent vomiting and hematocrit >=0.40 concurrent with platelet count <100 *
109/L.
PMID- 29344877
TI - A bioluminescent test system reveals valuable antioxidant properties of
lactobacillus strains from human microbiota.
AB - Oxidative stress cause serious damages in human organism resulting in multiple
diseases. Antioxidant therapy includes diet, the use of chemical agents or
commensal bacteria such as lactobacilli. This study aims to evaluate the
antioxidant (AO) activity of cell-free culture supernatants of lactobacilli,
isolated from different parts of the human body. A test system based on
Escherichia coli MG1655 strains carrying plasmids encoding luminescent biosensors
pSoxS-lux and pKatG-lux inducible by superoxide anion and hydrogen peroxide,
respectively, was used to analyze cell-free culture supernatants of lactobacilli.
Bioluminescent detection systems are suitable for quick screening of AO activity
of lactobacilli. The majority of strains (51 out of 81) belonging to six
different species demonstrated various levels of antioxidant activity. This
activity was confirmed using the trolox equivalent method. The genome of one of
the strains showing high AO activity was sequenced, and the genes putatively
involved in AO capacity were determined. Potencies of standard AO and CFS from
the most active Lactobacillus strains. Percentages of decrease in the detected
luminescence (IAO%) in the presence of AO or CFS are presented. L. br.-L. brevis,
L. pl. -L. plantarum, L. rh.-L. rhamnosus.
PMID- 29344876
TI - Biosimilarity and Interchangeability: Principles and Evidence: A Systematic
Review.
AB - BACKGROUND: The efficacy, safety and immunogenicity risk of switching between an
originator biologic and a biosimilar or from one biosimilar to another are of
potential concern. OBJECTIVES: The aim was to conduct a systematic literature
review of the outcomes of switching between biologics and their biosimilars and
identify any evidence gaps. METHODS: A systematic literature search was conducted
in PubMed, EMBASE and Cochrane Library from inception to June 2017. Relevant
societal meetings were also checked. Peer-reviewed studies reporting efficacy
and/or safety data on switching between originator and biosimilar products or
from one biosimilar to another were selected. Studies with fewer than 20 switched
patients were excluded. Data were extracted on interventions, study population,
reason for treatment switching, efficacy outcomes, safety and anti-drug
antibodies. RESULTS: The systematic literature search identified 63 primary
publications covering 57 switching studies. The reason for switching was reported
as non-medical in 50 studies (23 clinical, 27 observational). Seven studies (all
observational) did not report whether the reasons for switching were medical or
non-medical. In 38 of the 57 studies, fewer than 100 patients were switched.
Follow-up after switching went beyond 1 year in eight of the 57 studies. Of the
57 studies, 33 included statistical analysis of disease activity or patient
outcomes; the majority of these studies found no statistically significant
differences between groups for main efficacy parameters (based on P < 0.05 or
predefined acceptance ranges), although some studies observed changes for some
parameters. Most studies reported similar safety profiles between groups.
CONCLUSIONS: There are important evidence gaps around the safety of switching
between biologics and their biosimilars. Sufficiently powered and appropriately
statistically analysed clinical trials and pharmacovigilance studies, with long
term follow-ups and multiple switches, are needed to support decision-making
around biosimilar switching.
PMID- 29344878
TI - Gemcitabine and Taxane Adjuvant Therapy with Chemoradiation in Resected
Pancreatic Cancer: A Novel Strategy for Improved Survival?
AB - BACKGROUND: Gemcitabine-taxane combination chemotherapy has demonstrated a
survival benefit clinically in metastatic pancreatic cancer (PC). The authors
present their experience with gemcitabine and docetaxel (gem/tax)-based adjuvant
treatment (Rx) after surgery with curative intent. METHODS: Patients with de novo
resectable PC from January 2010 to December 2015 were identified from the
authors' institutional database and registry. The study included only patients
who received gem/tax as their initial Rx administered exclusively at the authors'
institution with or without chemoradiation (CRTx). Survival analysis was
performed using Kaplan-Meier methods, and prognostic factors were investigated by
Cox proportional hazard modeling. RESULTS: Of 102 patients identified, 58 met the
study criteria. The median age at diagnosis was 65 years, with 55% of the
patients undergoing an R1 resection (margin <= 1 mm). Tumor characteristics
included a median tumor size of 28 mm, a poor differentiation rate of 54%, and a
lymph node positivity of 67%. Most of the patients (90%, 52/58) completed 80% or
more of the 24 week Rx. Of these patients, 71% received post-gem/tax CRTx Rx.
Grade 3 or 4 toxicity was observed in 52% of the patients. The median follow-up
period was 51.2 months, and the observed median overall survival (OS) was 52
months [95% confidence interval (CI) 27.4-not reached]. The actuarial 5-year OS
was 49% (95% CI 33.7-63.4%). In the multivariate analysis, an R1 resection and
American Joint Committee on Cancer (AJCC) stage 2 versus stage 1 disease were
negatively associated with OS, whereas administration of CRTx was positively
associated with OS. CONCLUSIONS: Adjuvant gem/tax with or without CRTx is
feasible, with a favorable OS. Future prospective studies of gem/taxane-based
adjuvant Rx for PC are warranted.
PMID- 29344879
TI - Antiplatelet (aspirin) therapy as a new option in the treatment of vasculogenic
erectile dysfunction: a prospective randomized double-blind placebo-controlled
study.
AB - PURPOSE: To investigate the efficiency of antiplatelet (aspirin) therapy in
vasculogenic erectile dysfunction (VED) patients with a high mean platelet
volume. METHODS: A total of 184 patients diagnosed with VED between the ages of
18 and 76 were randomly divided into two groups and treated for 6 weeks [group 1:
120 patients (mean age 48.3), aspirin 100 mg/day; group 2: 64 patients (mean age
47.7), placebo 100 mg/day]. The changes from baseline to end point in erectile
function scores on the International Index of Erectile Function (IIEF-EF) and the
number of patients who answered "yes" to questions 2 and 3 of the sexual
encounter profile (SEP) were compared statistically. RESULTS: The mean baseline
IIEF-EF scores in groups 1 and 2 were 14.1 +/- 4.9 and 14.3 +/- 5.2, respectively
(p = 0.7966), the number of patients who answered "yes" to SEP-2 was 62 (51.6%)
in group 1 and 32 (50%) in group 2 (p = 0.8366), and the number of patients who
answered "yes" to SEP-3 was 38 (31.6%) in group 1 and 20 (31.2%) in group 2 (p =
0.9557). In the aspirin group, the changes from baseline to end point in the IIEF
EF, SEP-2, and SEP-3 scores were 7.2, 36.6, and 46.6%, respectively. In the
placebo group, these changes were 2.0, 9.4, and 12.5%, respectively. When
compared with the placebo group, aspirin-treated subjects showed a significant
improvement in all three efficacy measures (p < 0.0001). CONCLUSIONS: 100 mg of
aspirin administered once a day significantly improved EF in men with VED.
PMID- 29344880
TI - The role of zinc in urinary stone disease.
AB - In recent years, the role of trace elements in lithogenesis has received steadily
increasing attention. It is well documented that some trace elements can
influence the morphology and speed of the crystallization process. Zinc has been
found in significant amounts in calcium stones relative or organic stones (uric
acid and cystine), probably substituting calcium in crystals because of their
similarity in charge and size. High Zn levels are present in carbapatite of
Randal's plaques suggesting that zinc could promote calcium phosphate deposition
in the medullar interstitium. Large-scale epidemiological studies have found an
association of increased dietary zinc intake with increased risk of
nephrolithiasis in adults but not in adolescents. Most studies examining urinary
zinc levels in adults have reported increased urinary Zn excretion in stone
formers. In an experimental model of organic crystal formation produced by
silencing xanthine dehydrogenase in Drosophila fly, maneuvers that reduce Zn
excretion have shown to reduce crystal formation in the lumen of the Malpighian
tubules. This is curious because this is not a model of calcium stone formation.
Finally, zinc supplementation has been associated with increased admissions for
urinary lithiasis in men, but no change in calcium stone formation in children.
Perhaps, some of these contradicting findings can be explained in part by the in
vitro effect of zinc on the type and amount of calcium phosphate formed: At low
concentrations, Zn inhibited the crystal growth of dicalcium phosphate dihydrate,
octacalcium phosphate, and apatite, and at higher concentrations, it promoted the
formation of amorphous calcium phosphate. Thus, further studies are needed to see
whether manipulation of Zn metabolism can inhibit calcium stone formation.
PMID- 29344882
TI - Detection of Combinatorial Mutational Patterns in Human Cancer Genomes by
Exclusivity Analysis.
AB - Cancer genes may tend to mutate in a co-mutational or mutually exclusive manner
in a tumor sample of a specific cancer, which constitute two known combinatorial
mutational patterns for a given gene set. Previous studies have established that
genes functioning in different signaling pathways can mutate in the same sample,
i.e., a tumor from one patient, while genes operating in the same pathway are
rarely mutated in the same cancer genome. Therefore, reliable identification of
combinatorial mutational patterns of candidate cancer genes has important
ramifications in inferring signaling network modules in a particular cancer type.
While algorithms for discovering mutated driver pathways based on mutual
exclusivity of mutations in cancer genes have been proposed, a systematic
pipeline for identifying both co-mutational and mutually exclusive patterns with
rational significance estimation is still lacking. Here, we describe a reliable
framework with detailed procedures to simultaneously explore both combinatorial
mutational patterns from public cross-sectional gene mutation data.
PMID- 29344883
TI - Discovering Altered Regulation and Signaling Through Network-based Integration of
Transcriptomic, Epigenomic, and Proteomic Tumor Data.
AB - With the extraordinary rise in available biological data, biologists and
clinicians need unbiased tools for data integration in order to reach accurate,
succinct conclusions. Network biology provides one such method for high
throughput data integration, but comes with its own set of algorithmic problems
and needed expertise. We provide a step-by-step guide for using Omics Integrator,
a software package designed for the integration of transcriptomic, epigenomic,
and proteomic data. Omics Integrator can be found at
http://fraenkel.mit.edu/omicsintegrator .
PMID- 29344881
TI - The impact of exercise on physical function, cardiovascular outcomes and quality
of life in chronic kidney disease patients: a systematic review.
AB - The prevalence of chronic kidney disease (CKD) and end-stage renal disease (ESRD)
is increasing steadily. CKD does not only relate to morbidity and mortality but
also has impact on quality of life, depression and malnutrition. Such patients
often have significantly decreased physical activity. Recent evidence suggests
that low physical activity is associated with morbidity, mortality, muscle
atrophy, quality of life impairment, cardiovascular outcomes and depression.
Based on this, it is now recommended to regularly improve the physical activity
of these patients. Furthermore, studies have shown the beneficial effects of
various exercise programs with respect to outcomes such as low physical activity
muscle atrophy, quality of life, cardiovascular outcomes and depression. Despite
these encouraging findings, the subject is still under debate, with various
aspects still unknown. In this review, we tried to critically summarize the
existing studies, to explore mechanisms and describe future perspectives
regarding physical activity in CKD/ESRD patients.
PMID- 29344884
TI - Analyzing DNA Methylation Patterns During Tumor Evolution.
AB - Epigenetic modifications play a key role in cellular development and
tumorigenesis. Recent large-scale genomic studies have shown that mutations in
players of the epigenetic machinery and concomitant perturbation of epigenomic
patterning are frequent events in tumors. Among epigenetic marks, DNA methylation
is one of the best studied. Hyper- and hypo-methylation events of specific
regulatory elements (such as promoters and enhancers) are sometimes thought to be
correlated with expression of nearby genes. High-throughput bisulfite converted
sequencing is currently the technology of choice for studying DNA methylation in
base-pair resolution and on whole-genome scale. Such broad and high-resolution
coverage investigations of the epigenome provide unprecedented opportunities to
analyze DNA methylation patterns, which are correlated with tumorigenesis, tumor
evolution, and tumor progression. However, few computational pipelines are
available to the public to perform systematic DNA methylation analysis. Utilizing
open source tools, we here describe a comprehensive computational methodology to
thoroughly analyze DNA methylation patterns during tumor evolution based on
bisulfite converted sequencing data, including intra-tumor methylation
heterogeneity.
PMID- 29344885
TI - MicroRNA Networks in Breast Cancer Cells.
AB - A variety of molecular techniques can be used in order to unravel the molecular
composition of cells. In particular, the microarray technology has been used to
identify novel biomarkers that may be useful in the diagnosis, prognosis, or
treatment of cancer. The microarray technology is ideal for biomarker discovery
as it allows for the screening of a large number of molecules at once. In this
review, we focus on microRNAs (miRNAs) which are key molecules in cells and
regulate gene expression post-transcriptionally. miRNAs are small, single
stranded RNA molecules that bind to complementary mRNAs. Binding of miRNAs to
mRNAs leads either to degradation, or translational inhibition of the target
mRNA. Roughly one third of all the mRNAs are postulated to be regulated by
miRNAs. miRNAs are known to be deregulated in different types of cancer,
including breast cancer, and it has been demonstrated that deregulation of
several miRNAs can be used as biological markers in cancer. miRNA expression can
for example discriminate between normal, benign and malignant breast tissue, and
between different breast cancer subtypes.In the post-genomic era, an important
task of molecular biology is to understand gene regulation in the context of
biological networks. Because miRNAs have such a pronounced role in cells, it is
pivotal to understand the mechanisms that underlie their control, and to identify
how miRNAs influence cancer development and progression.
PMID- 29344886
TI - Identifying Genetic Dependencies in Cancer by Analyzing siRNA Screens in Tumor
Cell Line Panels.
AB - Loss-of-function screening using RNA interference or CRISPR approaches can be
used to identify genes that specific tumor cell lines depend upon for survival.
By integrating the results from screens in multiple cell lines with molecular
profiling data, it is possible to associate the dependence upon specific genes
with particular molecular features (e.g., the mutation of a cancer driver gene,
or transcriptional or proteomic signature). Here, using a panel of kinome-wide
siRNA screens in osteosarcoma cell lines as an example, we describe a
computational protocol for analyzing loss-of-function screens to identify genetic
dependencies associated with particular molecular features. We describe the steps
required to process the siRNA screen data, integrate the results with genotypic
information to identify genetic dependencies, and finally the integration of
protein-protein interaction data to interpret these dependencies.
PMID- 29344888
TI - Perseus: A Bioinformatics Platform for Integrative Analysis of Proteomics Data in
Cancer Research.
AB - Mass spectrometry-based proteomics is a continuously growing field marked by
technological and methodological improvements. Cancer proteomics is aimed at
pursuing goals such as accurate diagnosis, patient stratification, and biomarker
discovery, relying on the richness of information of quantitative proteome
profiles. Translating these high-dimensional data into biological findings of
clinical importance necessitates the use of robust and powerful computational
tools and methods. In this chapter, we provide a detailed description of standard
analysis steps for a clinical proteomics dataset performed in Perseus, a software
for functional analysis of large-scale quantitative omics data.
PMID- 29344889
TI - Quantitative Analysis of Tyrosine Kinase Signaling Across Differentially Embedded
Human Glioblastoma Tumors.
AB - Glioblastoma is the most aggressive primary brain tumor with a poor mean survival
even with the current standard of care. Kinase signaling analyses of clinical
glioblastoma samples provide a physiologically relevant view of oncogenic
signaling networks. Here, we describe the methods that enable the quantification
of protein expression profiles and phosphotyrosine signaling across flash frozen
and optimal cutting temperature (OCT) compound embedded tumor specimens. The data
derived from these experiments can be used to identify the intra- and inter
patient heterogeneity present in these tumors. Correlation and functional
analyses on the quantitative protein expression and phosphotyrosine signaling
data obtained from clinical samples can be used to identify tyrosine kinase
signaling networks present in these tumors and reveal the differential expression
of functionally related proteins. This chapter provides the quantitative mass
spectrometry methods required for the identification of in vivo oncogenic
signaling networks from human tumor specimens.
PMID- 29344887
TI - Phosphoproteomics-Based Profiling of Kinase Activities in Cancer Cells.
AB - Cellular signaling, predominantly mediated by phosphorylation through protein
kinases, is found to be deregulated in most cancers. Accordingly, protein kinases
have been subject to intense investigations in cancer research, to understand
their role in oncogenesis and to discover new therapeutic targets. Despite great
advances, an understanding of kinase dysfunction in cancer is far from complete.A
powerful tool to investigate phosphorylation is mass-spectrometry (MS)-based
phosphoproteomics, which enables the identification of thousands of
phosphorylated peptides in a single experiment. Since every phosphorylation event
results from the activity of a protein kinase, high-coverage phosphoproteomics
data should indirectly contain comprehensive information about the activity of
protein kinases.In this chapter, we discuss the use of computational methods to
predict kinase activity scores from MS-based phosphoproteomics data. We start
with a short explanation of the fundamental features of the phosphoproteomics
data acquisition process from the perspective of the computational analysis.
Next, we briefly review the existing databases with experimentally verified
kinase-substrate relationships and present a set of bioinformatic tools to
discover novel kinase targets. We then introduce different methods to infer
kinase activities from phosphoproteomics data and these kinase-substrate
relationships. We illustrate their application with a detailed protocol of one of
the methods, KSEA (Kinase Substrate Enrichment Analysis). This method is
implemented in Python within the framework of the open-source Kinase Activity
Toolbox (kinact), which is freely available at http://github.com/saezlab/kinact/
.
PMID- 29344890
TI - Prediction of Clinical Endpoints in Breast Cancer Using NMR Metabolic Profiles.
AB - Metabolic profiles reflect biological conditions as a result of biochemical
changes within a living system. It is therefore possible to associate metabolic
signatures with clinical endpoints of diseases, such as breast cancer. Nuclear
magnetic resonance (NMR) spectroscopy is one of the most common techniques used
for metabolic profiling, and produces high dimensional datasets from which
meaningful biological information can be extracted. Here, we present an overview
of data analysis techniques used to achieve this, describing key steps in the
procedure. Moreover, examples of clinical endpoints of interest are provided.
Although these are specific for breast cancer, the procedures for the analysis of
NMR spectra as described here are applicable to any type of cancer and to other
diseases.
PMID- 29344891
TI - Stochastic and Deterministic Models for the Metastatic Emission Process:
Formalisms and Crosslinks.
AB - Although the detection of metastases radically changes prognosis of and treatment
decisions for a cancer patient, clinically undetectable micrometastases hamper a
consistent classification into localized or metastatic disease. This chapter
discusses mathematical modeling efforts that could help to estimate the
metastatic risk in such a situation. We focus on two approaches: (1) a stochastic
framework describing metastatic emission events at random times, formalized via
Poisson processes, and (2) a deterministic framework describing the
micrometastatic state through a size-structured density function in a partial
differential equation model. Three aspects are addressed in this chapter. First,
a motivation for the Poisson process framework is presented and modeling
hypotheses and mechanisms are introduced. Second, we extend the Poisson model to
account for secondary metastatic emission. Third, we highlight an inherent
crosslink between the stochastic and deterministic frameworks and discuss its
implications. For increased accessibility the chapter is split into an informal
presentation of the results using a minimum of mathematical formalism and a
rigorous mathematical treatment for more theoretically interested readers.
PMID- 29344892
TI - Mechanically Coupled Reaction-Diffusion Model to Predict Glioma Growth:
Methodological Details.
AB - Biophysical models designed to predict the growth and response of tumors to
treatment have the potential to become a valuable tool for clinicians in care of
cancer patients. Specifically, individualized tumor forecasts could be used to
predict response or resistance early in the course of treatment, thereby
providing an opportunity for treatment selection or adaption. This chapter
discusses an experimental and modeling framework in which noninvasive imaging
data is used to initialize and parameterize a subject-specific model of tumor
growth. This modeling approach is applied to an analysis of murine models of
glioma growth.
PMID- 29344893
TI - Profiling Tumor Infiltrating Immune Cells with CIBERSORT.
AB - Tumor infiltrating leukocytes (TILs) are an integral component of the tumor
microenvironment and have been found to correlate with prognosis and response to
therapy. Methods to enumerate immune subsets such as immunohistochemistry or flow
cytometry suffer from limitations in phenotypic markers and can be challenging to
practically implement and standardize. An alternative approach is to acquire
aggregative high dimensional data from cellular mixtures and to subsequently
infer the cellular components computationally. We recently described CIBERSORT, a
versatile computational method for quantifying cell fractions from bulk tissue
gene expression profiles (GEPs). Combining support vector regression with prior
knowledge of expression profiles from purified leukocyte subsets, CIBERSORT can
accurately estimate the immune composition of a tumor biopsy. In this chapter, we
provide a primer on the CIBERSORT method and illustrate its use for
characterizing TILs in tumor samples profiled by microarray or RNA-Seq.
PMID- 29344894
TI - Systems Biology Approaches in Cancer Pathology.
AB - The complex network of the tissue system, in both pre-neoplastic tissues and
tumors, demonstrates the need for a systems biology approach to cancer pathology,
in which quantification of key tissue system processes is combined with
informatics tools to produce actionable scores to aid clinical decision-making. A
systems biology approach to cancer pathology enables integration of key system
features that are relevant to diagnoses, patient outcomes, and responses to
therapies. Key tissue system features relevant to cancer pathology include
molecular and morphologic abnormalities in epithelia, cellular changes in the
stroma such as immune infiltrates, and relationships between components of the
system, such as interactions and spatial relationships between epithelial and
stromal components, and also between specific immune cell subsets. Here, we
describe a method for objective quantification of multiple epithelial and stromal
biomarkers in the context of tissue architecture to generate a high dimensional
tissue profile that can be used to build multivariable predictive models for
cancer pathology.
PMID- 29344895
TI - Bioinformatics Approaches to Predict Drug Responses from Genomic Sequencing.
AB - Fulfilling the promises of precision medicine will depend on our ability to
create patient-specific treatment regimens. Therefore, being able to translate
genomic sequencing into predicting how a patient will respond to a given drug is
critical. In this chapter, we review common bioinformatics approaches that aim to
use sequencing data to predict sample-specific drug susceptibility. First, we
explain the importance of customized drug regimens to the future of medical care.
Second, we discuss the different public databases and community efforts that can
be leveraged to develop new methods for identifying new predictive biomarkers.
Third, we cover the basic methods that are currently used to identify markers or
signatures of drug response, without any prior knowledge of the drug's mechanism
of action. We further discuss how one can integrate knowledge about drug targets,
mechanisms, and predictive markers to better estimate drug response in a diverse
set of samples. We begin this section with a primer on popular methods to
identify targets and mechanism of action for new small molecules. This discussion
also includes a set of computational methods that incorporate other drug
features, which do not relate to drug-induced genetic changes or sequencing data
such as drug structures, side-effects, and efficacy profiles. Those additional
drug properties can aid in gaining higher accuracy for the identification of drug
target and mechanism of action. We then progress to discuss using these targets
in combination with disease-specific expression patterns, known pathways, and
genetic interaction networks to aid drug choice. Finally, we conclude this
chapter with a general overview of machine learning methods that can integrate
multiple pieces of sequencing data along with prior drug or biological knowledge
to drastically improve response prediction.
PMID- 29344896
TI - A Robust Optimization Approach to Cancer Treatment under Toxicity Uncertainty.
AB - The design of optimal protocols plays an important role in cancer treatment.
However, in clinical applications, the outcomes under the optimal protocols are
sensitive to variations of parameter settings such as drug effects and the
attributes of age, weight, and health conditions in human subjects. One approach
to overcoming this challenge is to formulate the problem of finding an optimal
treatment protocol as a robust optimization problem (ROP) that takes parameter
uncertainty into account. In this chapter, we describe a method to model toxicity
uncertainty. We then apply a mixed integer ROP to derive the optimal protocols
that minimize the cumulative tumor size. While our method may be applied to other
cancers, in this work we focus on the treatment of chronic myeloid leukemia (CML)
with tyrosine kinase inhibitors (TKI). For simplicity, we focus on one particular
mode of toxicity arising from TKI therapy, low blood cell counts, in particular
low absolute neutrophil count (ANC). We develop optimization methods for locating
optimal treatment protocols assuming that the rate of decrease of ANC varies
within a given interval. We further investigated the relationship between
parameter uncertainty and optimal protocols. Our results suggest that the dosing
schedule can significantly reduce tumor size without recurrence in 360 weeks
while insuring that toxicity constraints are satisfied for all realizations of
uncertain parameters.
PMID- 29344897
TI - Modeling of Interactions between Cancer Stem Cells and their Microenvironment:
Predicting Clinical Response.
AB - Mathematical models of cancer stem cells are useful in translational cancer
research for facilitating the understanding of tumor growth dynamics and for
predicting treatment response and resistance to combined targeted therapies. In
this chapter, we describe appealing aspects of different methods used in
mathematical oncology and discuss compelling questions in oncology that can be
addressed with these modeling techniques. We describe a simplified version of a
model of the breast cancer stem cell niche, illustrate the visualization of the
model, and apply stochastic simulation to generate full distributions and average
trajectories of cell type populations over time. We further discuss the advent of
single-cell data in studying cancer stem cell heterogeneity and how these data
can be integrated with modeling to advance understanding of the dynamics of
invasive and proliferative populations during cancer progression and response to
therapy.
PMID- 29344898
TI - Methods for High-throughput Drug Combination Screening and Synergy Scoring.
AB - Gene products or pathways that are aberrantly activated in cancer but not in
normal tissue hold great promises for being effective and safe anticancer
therapeutic targets. Many targeted drugs have entered clinical trials but so far
showed limited efficacy mostly due to variability in treatment responses and
often rapidly emerging resistance. Toward more effective treatment options, we
will need multi-targeted drugs or drug combinations, which selectively inhibit
the viability and growth of cancer cells and block distinct escape mechanisms for
the cells to become resistant. Functional profiling of drug combinations requires
careful experimental design and robust data analysis approaches. At the Institute
for Molecular Medicine Finland (FIMM), we have developed an experimental
computational pipeline for high-throughput screening of drug combination effects
in cancer cells. The integration of automated screening techniques with advanced
synergy scoring tools allows for efficient and reliable detection of synergistic
drug interactions within a specific window of concentrations, hence accelerating
the identification of potential drug combinations for further confirmatory
studies.
PMID- 29344901
TI - Imaging Characteristics and First Experience of [68Ga]THP-PSMA, a Novel Probe for
Rapid Kit-Based Ga-68 Labeling and PET Imaging: Comparative Analysis with
[68Ga]PSMA I&T.
AB - PURPOSE: [68Ga]Trishydroxypyridinone (THP)-prostate-specific membrane antigen
(PSMA) is a novel tracer that can be labeled in one step by cold reconstitution
of a kit with unprocessed generator eluate, targeting PSMA via the lysine-urea
glutamate (KuE) motif. The aim of this study was to evaluate the human imaging
characteristics of [68Ga]THP-PSMA. PROCEDURES: [68Ga]THP-PSMA positron emission
tomography (PET)/x-ray computed tomography (CT) was performed in 25 patients with
biochemical recurrence after radical prostatectomy for prostate cancer. Urinary
and biliary excretion and tumor lesion uptake were quantified using standardized
uptake values (SUVs). Imaging characteristics were assessed in terms of non
target organ uptake, background activity, target-to-background ratios (TBRs) of
tumor lesions, and frequency of bladder halo artifacts. Findings were compared to
a matched cohort of 25 patients undergoing PET/CT with the established agent
[68Ga]PSMA I&T. RESULTS: Physiologic uptake of [68Ga]THP-PSMA was significantly
lower in salivary glands (P < 0.0001), liver (P < 0.0001), spleen (P < 0.0001),
and kidneys (P < 0.0001) than with [68Ga]PSMA I&T. While biliary tracer excretion
of [68Ga]THP-PSMA was negligible, urinary tracer excretion of [68Ga]THP-PSMA was
fast, and significantly higher than for [68Ga]PSMA I&T, contributing to a higher
frequency of bladder artifacts. Malignant lesion uptake of [68Ga]THP-PSMA
assessed as either SUV or TBR was significantly lower than with [68Ga]PSMA I&T.
CONCLUSION: [68Ga]THP-PSMA yields suitable in vivo uptake characteristics. The
simplified synthesis method for [68Ga]THP-PSMA may facilitate wider application
and higher patient throughput with PSMA imaging. However, direct intraindividual
comparison studies are needed to assess the relative performance of [68Ga]THP
PSMA vs other PSMA ligands in terms of clinical detection rate and image quality.
PMID- 29344902
TI - Occupational exposure to electromagnetic fields in magnetic resonance
environment: basic aspects and review of exposure assessment approaches.
AB - The purpose of this review is to make a contribution to build a comprehensive
knowledge of the main aspects related to the occupational exposure to
electromagnetic fields (EMFs) in magnetic resonance imaging (MRI) environments.
Information has been obtained from original research papers published in
international peer-reviewed journals in the English language and from documents
published by governmental bodies and authorities. An overview of the occupational
exposure scenarios to static magnetic fields, motion-induced, time-varying
magnetic fields, and gradient and radiofrequency fields is provided, together
with a summary of the relevant regulation for limiting exposure. A particular
emphasis is on reviewing the main EMF exposure assessment approaches found in the
literature. Exposure assessment is carried out either by measuring the
unperturbed magnetic fields in the MRI rooms, or by personal monitoring
campaigns, or by the use of numerical methods. A general lack of standardization
of the procedures and technologies adopted for exposure assessment has emerged,
which makes it difficult to perform a direct comparison of results from different
studies carried out by applying different assessment strategies. In conclusion,
exposure assessment approaches based on data collection and numerical models need
to be better defined in order to respond to specific research questions. That
would provide for a more complete characterization of the exposure patterns and
for identification of the factors determining the exposure variability. Graphical
abstract Main approaches adopted in the literature to perform occupational
exposure assessment to electromagnetic fields (EMFs) in magnetic resonance
imaging (MRI) environments. SMF: static magnetic field; GMF: gradient magnetic
fields; RF: radio-frequencies.
PMID- 29344903
TI - Nuclear genes involved in mitochondrial diseases caused by instability of
mitochondrial DNA.
AB - Mitochondrial diseases are defined by a respiratory chain dysfunction and in most
of the cases manifest as multisystem disorders with predominant expression in
muscles and nerves and may be caused by mutations in mitochondrial (mtDNA) or
nuclear (nDNA) genomes. Most of the proteins involved in respiratory chain
function are nuclear encoded, although 13 subunits of respiratory chain complexes
(together with 2 rRNAs and 22 tRNAs necessary for their translation) encoded by
mtDNA are essential for cell function. nDNA encodes not only respiratory chain
subunits but also all the proteins responsible for mtDNA maintenance, especially
those involved in replication, as well as other proteins necessary for the
transcription and copy number control of this multicopy genome. Mutations in
these genes can cause secondary instability of the mitochondrial genome in the
form of depletion (decreased number of mtDNA molecules in the cell), vast
multiple deletions or accumulation of point mutations which in turn leads to
mitochondrial diseases inherited in a Mendelian fashion. The list of genes
involved in mitochondrial DNA maintenance is long, and still incomplete.
PMID- 29344904
TI - MGMT assessment in pituitary adenomas: comparison of different
immunohistochemistry fixation chemicals.
AB - PURPOSE: Despite the established role of O6-methyl-guanine-DNA methyltransferase
(MGMT) as a marker for temozolomide response, consensus of the most reliable
method to assess MGMT expression in pituitary adenomas is still missing.
Currently, immunohistochemistry (IHC) assessment of formaldehyde fixed tissue
samples is most widely used in a semiquantitative description. As formaldehyde
fails to completely preserve nucleic acids, RCL2, an alcohol-based formaldehyde
free fixative, has been proposed as a more reliable alternative in terms of cell
stability. Furthermore, as the current method of IHC is semiquantitative and
observer-dependent, pyrosequencing, an objective tool to evaluate the methylation
status of the MGMT promoter, has emerged as a reliable and accurate alternative.
The aim of this study was to validate the current IHC method for assessment of
MGMT protein expression in pituitary adenomas. METHODS: The tissue samples of 8
macroadenomas with positive IHC MGMT expression (> 50%) were investigated: first,
we compared the time dependent stability of MGMT protein expression after
pituitary adenoma removal between formaldehyde vs. RCL2. Then, we compared
positive IHC MGMT expression with methylated promoter status using
pyrosequencing. RESULTS: In the first 12 h after adenoma removal, tissue samples
remained MGMT positive in significantly more samples when fixated with
formaldehyde than with RCL2, respectively (96 vs. 81%, p = 0.025). CONCLUSION:
Our data confirm that the current method using formaldehyde tissue fixation and
IHC reveals stable and reliable results of MGMT assessment in pituitary adenomas.
PMID- 29344905
TI - Management of NFAs: medical treatment.
AB - INTRODUCTION: Non-functioning pituitary adenomas (NFPAs) are in general large
tumors that present with symptoms secondary to local pressure on adjacent
structures. Transsphenoidal surgery is the first line of treatment but residual
tumor mass is often detected post-operatively. Medical therapy, in any stage of
tumor management, is not well established. METHODS: A literature search was
performed to review the available data on medical treatment of NFPAs. RESULTS:
Medications investigated for the treatment of NFPAs include dopamine receptor
agonists (DA) and somatostatin receptor ligands. Randomized controlled trials are
lacking, but available data suggest that DA have a positive effect on tumor
remnant stabilization after surgery and could be considered in this setting.
Temozolomide is reserved for aggressive tumors, although future studies are
required. CONCLUSIONS: NFPA are often not amenable to complete surgical
resection. Conservative follow-up after surgery is associated with a high
prevalence of tumor remnant progression. DA therapy may prevent residual tumor
enlargement in over 85% of these patients, with a substantial consequent
reduction in the need for repeat surgery or radiation therapy. It is our view
that DA treatment should be routinely considered for the management of NFPA
patients with incompletely resected tumors.
PMID- 29344906
TI - Mortality in patients with non-functioning pituitary adenoma.
AB - Non-functioning pituitary adenomas (NFA) are benign pituitary neoplasms not
associated with clinical evidence of hormonal hypersecretion. A substantial
number of patients with NFA have morbidities related to the tumor and possible
recurrence(s), as well as to the treatments offered. Studies assessing the long
term mortality of patients with NFA are limited. Based on the published
literature of the last two decades, overall, the standardized mortality ratios in
this group suggest mortality higher than that of the general population with
deaths attributed mainly to circulatory, respiratory and infectious causes. Women
seem to have higher mortality ratios, and assessment of time trends suggests
improvement over the years. There is no consensus on predictive factors of
mortality but those most consistently identified are older age at diagnosis and
high doses of glucocorticoid substitution therapy. Well designed and of adequate
power studies are needed to establish the significance of factors compromising
the survival of patients with NFA and to facilitate improvements in long-term
prognosis.
PMID- 29344907
TI - Silent corticotroph adenomas.
AB - PURPOSE: Silent corticotroph adenomas (SCAs) present clinically as non
functioning adenomas (NFAs) but are immunopositive for adrenocorticotrophic
hormone (ACTH) without biochemical and clinical manifestation of
hypercortisolism. Pathologic examination of resected NFAs that demonstrate
positive ACTH and/or TPIT expression confirms its corticotroph lineage. SCAs
comprise up to 20% of NFAs and exhibit a higher rate of recurrence. Studies of
molecular mechanisms have generated multiple hypotheses on SCA tumorigenesis,
pathophysiology, and growth that as yet remain to be proven. An improved
understanding of their pathologic and clinical characteristics is needed.
METHODS: A literature review was performed using PubMed to identify research
reports and clinical case series on SCAs. RESULTS: Up to date findings regarding
epidemiology, mechanisms of pathogenesis, differentiation, progression, and
growth, as well as clinical presentation, postoperative course, and treatment
options for patients with SCAs are presented. Pooled results demonstrate that 25
40% of cases show cavernous sinus invasion, preoperative hypopituitarism, new
onset hypopituitarism, and recurrence. CONCLUSION: This article reviews the
incidence, molecular pathology, and clinical behavior of these unique non
functioning pituitary corticotroph adenomas, and highlights the need for rigorous
monitoring for recurrences and hypopituitarism in patients with SCAs.
PMID- 29344908
TI - Encoding differences affect the number and precision of own-race versus other
race faces stored in visual working memory.
AB - Other-race faces are discriminated and recognized less accurately than own-race
faces. Despite a wealth of research characterizing this other-race effect (ORE),
little is known about the nature of the representations of own-race versus other
race faces. This is because traditional measures of this ORE provide a binary
measure of discrimination or recognition (correct/incorrect), failing to capture
potential variation in the quality of face representations. We applied a novel
continuous-response paradigm to independently measure the number of own-race and
other-race face representations stored in visual working memory (VWM) and the
precision with which they are stored. Participants reported target own-race or
other-race faces on a circular face space that smoothly varied along the
dimension of identity. Using probabilistic mixture modeling, we found that
following ample encoding time, the ORE is attributable to differences in the
probability of a face being maintained in VWM. Reducing encoding time, a
manipulation that is more sensitive to encoding limitations, caused a loss of
precision or an increase in variability of VWM for other-race but not own-race
faces. These results suggest that the ORE is driven by the inefficiency with
which other-race faces are rapidly encoded in VWM and provide novel insights
about how perceptual experience influences the representation of own-race and
other-race faces in VWM.
PMID- 29344909
TI - Flash-induced forward and reverse illusory line motion in offset bars.
AB - Illusory line motion (ILM) refers to perception of motion in a bar that onsets or
offsets all at once. When the bar onsets or offsets between two boxes after one
of the boxes flashes, the bar appears to shoot out of the flashed box (flashILM).
If the bar offsets during the flash, it appears to contract into the flashed box
(reverse ILM; rILM). Onset bars do not show rILM. Moreover, rILM and flashILM are
not correlated, indicating they are two different illusions. To date, rILM has
only been studied using a 50-ms flash where the bar offsets 16.7 ms after flash
onset. It is not clear if rILM is due to the 16.7-ms flash-bar-removal stimulus
onset asynchrony (SOA) or due to the flash offsetting after the bar. The current
studies explore these parameters to better understand the conditions that lead to
rILM. The results suggest that flashILM is sensitive to the temporal interval
between flash onset and bar offset, while rILM appears to arise when the flash
offsets after the bar has been removed regardless of the temporal interval
between flash onset and bar removal. These results are consistent with flashILM
reflecting visual exogenous attention while rILM may reflect the low-level
spreading of subthreshold activation radiating from the flashed box. The findings
are incorporated into the recent work that suggests that the literature
concerning ILM is possibly conflating a number of different illusions of line
motion, including polarized gamma motion (PGM), transformational apparent motion
(TAM), and exogenous attention induced motion (flashILM).
PMID- 29344910
TI - Mimesis and clinical pictures: thinking with Plato and Broekman through the
production and meaning of images of disease.
AB - This paper contends, following Plato and Broekman, that (1) seeing images as
images is crucial to theorizing medicine and that (2) considering clinical
pictures as images of images is a much-needed epistemic complement to the
domineering view that sees clinical pictures as mirrors of disease. This does not
only offer epistemic, but also ethical benefits to individual patients,
especially in those cases where patients suffer from chronic, debilitating, and
terminal illnesses and where medicine provides no, or limited, answers in terms
of treatment, intervention, and meaning. By creating room for a theory of
clinical pictures that rightfully emphasizes its pictorial nature, patients and
doctors alike may be encouraged to consider under what authorship, and with which
epistemic tools, alternative, supplemental images may be produced to get at the
existential reality of disease and suffering. Ultimately, this paper argues that
the epistemic tools provided by aesthetics may offer such glimpses into the
reality of disease and suffering, and I conclude by discussing a few artistic
renditions of breast cancer to illustrate my point.
PMID- 29344911
TI - Recurrent infectious subcapsular renal hematoma accompanied by microaneurysm.
AB - An 80-year-old woman was admitted to the hospital complaining of loss of
appetite. 10 days earlier, her oral intake gradually decreased with no other
specific symptoms, such as abdominal pain, nausea, vomiting, headache, or low
back pain. Abdominal computed tomography (CT) scan revealed a left subcapsular
renal hematoma. We suspected infective subcapsular renal hematoma, so
percutaneous needle aspiration and drainage were performed. Intravenous sulbactam
ampicillin was started immediately. On day 9 after admission, repeat CT scan
revealed the subcapsular hematoma had reduced in size. The drain was removed, and
intravenous antibiotics were discontinued. Follow-up CT scan on day 21 revealed
increased subcapsular renal hematoma size. The patient also had high fever.
Suspecting recurrence of infective subcapsular renal hematoma, we repeated the
drainage of the hematoma and restarted intravenous antibiotics. Renal
arteriography showed a renal artery microaneurysm and her condition improved with
renal artery embolization. Renal arteriography was useful for detecting renal
artery microaneurysm in infective subcapsular renal hematoma that did not resolve
after antibiotic treatment and drainage.
PMID- 29344912
TI - Capillary leak syndrome as a complication of antibody-mediated rejection
treatment: a case report.
AB - We report a case of capillary leak that developed during treatment of antibody
mediated rejection in a kidney transplant recipient. A 53-year-old female
transplant recipient experienced an increase in serum creatinine from 1.1 to 1.8
mg/dL. Antibody-mediated rejection was diagnosed by graft biopsy. She was treated
with five plasmapheresis sessions (on alternate days with albumin replacement),
five doses of immunoglobulin (5 g/dose at 100 mg/kg), a single dose of rituximab
(500 mg), and four doses of bortezomib on days 1, 4, 7, and 10 (1.72 mg/dose at
1.3 mg/m2 body surface area). During treatment, edema, slight diarrhea,
pancytopenia, hypoalbuminemia, peripheral neuropathy, and postural hypotension
were noted. Despite control of liquids, she presented with edema progressing to
an increase of more than 10 kg body weight. Prerenal acute graft dysfunction
associated with hypotension was diagnosed on day 12, heart failure or other
infectious complications being discounted. On day 13, daily hemodialysis was
prescribed, and a stable volume status was reached after five hemodialysis
sessions. On day 20, the patient recovered diuresis and the edema and diarrhea
abated, but she remained on chronic hemodialysis. After excluding other causes of
distributive shock, the diagnosis of capillary leak syndrome was based on the
presence of hypotension, generalized edema, and hypoalbuminemia in the absence of
significant proteinuria. The concomitant presence of diarrhea, peripheral
neuropathy, and pancytopenia, suggest a possible causal role for bortezomib.
Awareness by clinicians of capillary leak syndrome associated with bortezomib
based treatment of AMR is paramount, despite its rarity.
PMID- 29344913
TI - Cardiac basal autophagic activity and increased exercise capacity.
AB - To investigate whether high-intensity interval training (HIIT) and continuous
moderate-intensity training (CMT) have different impacts on exercise performance
and cardiac function and to determine the influence of these exercise protocols
on modulating basal autophagy in the cardiac muscle of rats. Rats were assigned
to three groups: sedentary control (SC), CMT, and HIIT. Total exercise volume and
mean intensity were matched between the two protocols. After a 10-week training
program, rats were evaluated for exercise performance, including exercise
tolerance and grip strength. Blood lactate levels were measured after an
incremental exercise test. Cardiac function and morphology were assessed by
echocardiography. Western blotting was used to evaluate the expression of
autophagy and mitochondrial markers. Transmission electron microscopy was used to
evaluate mitochondrial content. The results showed that time to exhaustion and
grip strength increased significantly in the HIIT group compared with the SC and
CMT groups. Both training interventions significantly increased time to
exhaustion, reduced blood lactate level (after an incremental exercise test) and
induced adaptive changes in cardiac morphology, but without altering cardiac
systolic function. The greater improvements in exercise performance with the HIIT
than with the CMT protocol were related to improvement in basal autophagic
adaptation and mitochondria function in cardiac muscle. Mitochondria markers were
positively correlated with autophagy makers. This study shows that HIIT is more
effective for improving exercise performance than CMT and this improvement is
related to mitochondrial function and basal autophagic adaptation in cardiac
muscle.
PMID- 29344914
TI - High lithium tolerance of Apocynum venetum seeds during germination.
AB - Identification and use of lithium (Li) accumulator plants is a promising strategy
to remediate Li-contaminated soil. Apocynum venetum is reported as a Li
accumulator. However, its tolerance to Li salt during germination is still
unknown. The primary aim of this study was to investigate the effects of two Li
salts on seed germination of A. venetum. At the same concentrations, germination
percentages in LiCl solution were higher than that in Li2CO3 solution. At 25
degrees C, seeds germinated to 4-90% at 0-400 mmol L-1 LiCl and 3-91% at 0-150
mmol L-1 Li2CO3. Low concentration (0-50 mmol L-1) of LiCl did not significantly
affect germination percentage. The simulated critical value (when germination
percentage is 50%) in LiCl solution is 196 mmol L-1, and 36 mmol L-1 for Li2CO3.
Activity of alpha-amylase, contents of MDA, soluble sugar, and proline were
dramatically affected by Li salts, especially at medium and late germination
stages. When compared with control, alpha-amylase activity of seeds under 25 mmol
L-1 LiCl and 10 mmol L-1 Li2CO3 did not show significant difference. Germination
percentage and index, radicle length, and physiological parameters indicate A.
venetum seeds are highly tolerant to Li salts during germination, especially
LiCl.
PMID- 29344915
TI - Mechanistic investigation of visible light driven photocatalytic inactivation of
E. coli by Ag-AgCl/ZnFe2O4.
AB - In this study, photocatalytic inactivation of Escherichia coli was investigated
over magnetic nanocomposite Ag-AgCl/ZnFe2O4. The nanocomposite demonstrated
efficient photocatalytic activity by complete inactivation of the bacteria within
60 min of visible light irradiation. The anions HPO42- and SO42- were found to
play the most important role in the inhibition of photocatalytic inactivation of
E. coli. A systematic investigation of mechanism of photocatalytic bacterial
inactivation was carried out based on cell membrane injury test, scanning
electron microscopy (SEM) of bacterial morphology changes, Fourier transform
infrared (FTIR) spectroscopy of E. coli cells before and after treatment,
superoxide dismutase (SOD) and catalase (CAT) activity assay, and role of various
reactive oxygen species (ROS). The activities of SOD and CAT enzymes were found
to decrease due to the ROSs attacks during photocatalytic inactivation. The ROS
produced in the photocatalytic disinfection severely altered the bacterial
permeability and led to protein fragmentation, release of ions, and generation of
protein carbonyl derivatives. The leaked cytoplasmic substances and cell debris
were further degraded and, ultimately, mineralized with prolonged photocatalytic
treatment.
PMID- 29344917
TI - Non-cardiac uptake of technetium-99m pyrophosphate in transthyretin cardiac
amyloidosis.
AB - BACKGROUND: Technetium-based bone scintigraphy is rapidly becoming the most
common non-invasive imaging tool in the diagnosis of Transthyretin cardiac
amyloidosis (ATTR). Skeletal muscle uptake has been described with technetium-99m
3,3-diphosphono-1,2-propanodicarboxylic acid (TcDPD), and may account for masking
of bony uptake. We sought to investigate skeletal muscle uptake of technetium-99m
pyrophosphate (TcPYP) in patients with ATTR. METHODS AND RESULTS: This was a
retrospective analysis of 57 patients diagnosed with ATTR who underwent TcPYP
scintigraphy. Cardiac uptake was assessed on whole-body planar imaging using a
semiquantitative scale (grades 0 to 3) and on single-photon emission computed
tomography (SPECT) with CT attenuation correction using total myocardial counts
per voxel after a 3-hour incubation. Skeletal muscle (psoas and biceps),
vertebral body, LV myocardium, and blood pool mean counts were calculated. In the
cohort (age 78 +/- 9 years, 77% male, and 30% hereditary ATTR), there was no
visualized tracer uptake in skeletal muscle or soft tissue on qualitative SPECT
assessment. Total and blood pool-corrected uptake in the muscle groups were
significantly less than myocardium and bone (P < 0.001). Blood pool-corrected
muscle uptake was not associated with semiquantitative grade 3 vs 2 uptake (psoas
P = 0.66, biceps P = 0.13) or presence of hereditary ATTR (psoas P = 0.43, biceps
P = 0.69). As bony uptake decreased, there was no corresponding increase in
skeletal muscle uptake. CONCLUSIONS: In patients with ATTR cardiac amyloidosis,
skeletal muscle uptake of TcPYP is minimal when assessed by qualitative and
quantitative metrics, and is not significantly different in patients with grade 2
vs 3 semiquantitative uptake. The properties of this tracer may be different than
TcDPD with respect to non-cardiac uptake.
PMID- 29344916
TI - The acute effects of erythromycin and oxytetracycline on enhanced biological
phosphorus removal system: shift in bacterial community structure.
AB - Since extensive application, an increasing amount of antibiotics has been
released into wastewater treatment plants. In this study, the enhanced biological
phosphorus removal (EBPR) system was fed with synthetic wastewater containing
erythromycin (ERY) and oxytetracycline (OTC) for 7 days to evaluate the
variations of solution ortho-P (SOP), volatile fatty acid (VFA), poly
bhydroxyalkanoates (PHAs), specific oxygen uptake rater (SOUR), and microbial
community in the EBPR system. The obtained results showed that the P-removal
efficiency decreased to 0.0%, and at the end of the experiment, only less than
20% of the VFA could be consumed. Besides, the variable processes of P and PHAs
were destroyed. Moreover, to better grasp the inhibitory mechanism of
antibiotics, microbial community compositions of activated sludge sampled in all
reactors were investigated by high-throughput sequencing techniques. Results of
comparative and evolutionary analysis revealed that high concentrations (5 and 10
mg/L) of ERY and OTC could seriously shift microbial communities, while combined
antibiotics could induce more. Additionally, Accumulibacter and Competibacter
were two primary microorganisms at the genus level in the EBPR system.
Accumulibacter decreased seriously for exposure to antibiotics, while
Competibacter increased in all experimental reactors especially in combined
antibiotics reactor.
PMID- 29344918
TI - Artifact-free quantitative cardiovascular PET/MR imaging: An impossible dream?
PMID- 29344919
TI - The impact of patient-to-detector distance on LV volumes and TID index on SPECT
myocardial perfusion imaging: Emphasis on consistent patient-detector positioning
in stress and rest phases.
PMID- 29344920
TI - Inflammatory reaction of a pericardial foreign body after cardiac surgery.
PMID- 29344921
TI - Does simplified quantitative analysis of 18F-FDG PET in cardiac inflammatory
disease work?
PMID- 29344922
TI - Impact of renin-angiotensin-aldosterone system polymorphisms on myocardial
perfusion: Correlations with myocardial single photon emission computed
tomography-derived parameters.
AB - BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) has an important role in
atherosclerosis. We investigated the effects of six RAAS gene polymorphisms on
myocardial perfusion. METHODS AND RESULTS: We examined 810 patients with known or
suspected coronary artery disease (CAD) using stress-rest myocardial single
photon emission computed tomography. Summed stress score (SSS), summed rest score
(SRS), summed difference score (SDS), transient ischemic dilation (TID), and
lung/heart ratio (LHR) were recorded. The following gene polymorphisms were
investigated: angiotensin-converting enzyme (ACE) insertion/deletion (I/D),
angiotensinogen (AGT) M235T and T174M, angiotensin II type 1 receptor (AT1R)
A1166C, renin (REN) C5312T, and angiotensin II type 2 receptor (AT2R) C3123A. The
heterozygotes or homozygotes on ACE D allele were 7.54 times more likely to have
abnormal SSS, while the AGT (T174M) heterozygotes were 5.19 times more likely to
have abnormal SSS. The homozygotes of ACE D had significantly higher values on
TID and LHR, while the AGT (T174M) heterozygotes had higher values on TID. The
AT1R heterozygotes had greater odds for having SSS >= 3. The patients carried
AT1R homozygosity of C allele had significantly higher values on TID, while
heterozygotes of AT1R had significantly higher values on LHR. CONCLUSIONS: Among
the polymorphisms investigated, ACE D allele had the strongest association with
abnormal myocardial perfusion.
PMID- 29344923
TI - Potential effects of low-dose average CT on cardiac implantable electronic
devices.
AB - BACKGROUND: Average CT has been shown to be more accurate than conventional
helical CT in quantitation of the PET data. The risk of CT irradiation of a
cardiac implantable electronic device (CIED) causing an adverse event is low and
is generally outweighed by the clinical benefit of a medically indicated
examination. However, irradiation of CIED over one breath cycle in cine CT scan
for average CT could impose risks on a patient who is pacing dependent. The
purpose of this study was to demonstrate that low-dose average CT can be safe for
CIED. METHODS: A Medtronic CIED of model Protecta VR was submerged in a saline
bath for a series of 4-s cine CT scans on a GE CT scanner programmed to deliver a
2-cm-wide radiation at a dose rate of 0.9 to 41.2 mGy/s to the CIED. The number
of over-sensings was recorded as the interference of radiation to the CIED.
RESULTS: Dose rates >= 1.9 mGy/s caused over-sensing. The higher the dose rate,
the more over-sensings there were. The lowest dose rate of 0.9 mGy/s did not
cause any over-sensing. CONCLUSIONS: Low-dose average CT at 0.9 mGy/s can be safe
for a CIED patient who is pacing dependent.
PMID- 29344924
TI - Reliability of the 123I-mIBG heart/mediastinum ratio: Results of a multicenter
test-retest reproducibility study.
AB - A quantitative measurement, the Heart-to-Mediastinum (H/M) ratio of counts
derived from a planar acquisition approximately 4 hours after injection of 123I
mIBG, is a strong predictor of outcomes in patients with stable class II-III
heart failure and LVEF <= 35%. This study assessed the test-retest
reproducibility of the H/M ratio in such patients. 47 subjects with class II-III
systolic heart failure and LVEF <= 35% were tested at two time intervals
separated by 5 to 14 days. Subjects were imaged twice on the same camera using
the same radionuclide dose. Images were sent to a core analysis lab, where three
nuclear technologists independently determined the H/M ratios. The primary
endpoint was test-retest H/M ratio reproducibility calculated as the absolute
difference in mean value determined by the three readers. Mean subject age was 65
+/- 12 years, 85% were male, and mean BMI was 29 +/- 6 kg/m2. Mean injected
activity was 10.18 +/- 0.43 mCi for first dose and 10.09 +/- 0.52 mCi for the
second dose. The mean and SD values for first and repeat studies were almost
identical: the 95% confidence interval of the mean test-retest difference was
0.055 to 0.076. Bland-Altman plots showed no systematic effect of the H/M ratio
on the magnitude of the difference between replicate measurements. Inter-reader
measurements were nearly identical. There were no serious adverse events despite
exposure to 123I-mIBG on 2 occasions in a short time period. The Heart-to
Mediastinum ratio of 123I-mIBG is a consistent and highly reproducible
measurement in stable Class II to III heart failure patients.
PMID- 29344925
TI - Translating visual information into action predictions: Statistical learning in
action and nonaction contexts.
AB - Humans are sensitive to the statistical regularities in action sequences carried
out by others. In the present eyetracking study, we investigated whether this
sensitivity can support the prediction of upcoming actions when observing
unfamiliar action sequences. In two between-subjects conditions, we examined
whether observers would be more sensitive to statistical regularities in
sequences performed by a human agent versus self-propelled 'ghost' events.
Secondly, we investigated whether regularities are learned better when they are
associated with contingent effects. Both implicit and explicit measures of
learning were compared between agent and ghost conditions. Implicit learning was
measured via predictive eye movements to upcoming actions or events, and explicit
learning was measured via both uninstructed reproduction of the action sequences
and verbal reports of the regularities. The findings revealed that participants,
regardless of condition, readily learned the regularities and made correct
predictive eye movements to upcoming events during online observation. However,
different patterns of explicit-learning outcomes emerged following observation:
Participants were most likely to re-create the sequence regularities and to
verbally report them when they had observed an actor create a contingent effect.
These results suggest that the shift from implicit predictions to explicit
knowledge of what has been learned is facilitated when observers perceive another
agent's actions and when these actions cause effects. These findings are
discussed with respect to the potential role of the motor system in modulating
how statistical regularities are learned and used to modify behavior.
PMID- 29344926
TI - The Mexican Drug War and Early-Life Health: The Impact of Violent Crime on Birth
Outcomes.
AB - This study examines the relationship between exposure to violent crime in utero
and birth weight using longitudinal data from a household survey conducted in
Mexico. Controlling for selective migration and fertility, the results suggest
that early gestational exposure to the recent escalation of the Mexican Drug War
is associated with a substantial decrease in birth weight. This association is
especially pronounced among children born to mothers of low socioeconomic status
and among children born to mothers who score poorly on a mental health index.
PMID- 29344927
TI - Correction to: Protein Biomarkers and Neuroproteomics Characterization of
Microvesicles/Exosomes from Human Cerebrospinal Fluid Following Traumatic Brain
Injury.
AB - The original version of this article unfortunately contained a typographical
error on Author's name "Firas Kobessiy". This should be corrected as "Firas
Kobeissy".
PMID- 29344929
TI - Pla2g6 Deficiency in Zebrafish Leads to Dopaminergic Cell Death, Axonal
Degeneration, Increased beta-Synuclein Expression, and Defects in Brain Functions
and Pathways.
AB - This study aimed to gain insights into the pathophysiology underlying PLA2G6
associated neurodegeneration that is implicated in three different neurological
disorders, suggesting that other, unknown genetic or environmental factors might
contribute to its wide phenotypic expression. To accomplish this, we
downregulated the function of pla2g6 in the zebrafish nervous system, performed
parkinsonism-related phenotypic characterization, and determined the effects of
gene regulation upon the loss of pla2g6 function by using RNA sequencing and
downstream analyses. Pla2g6 deficiency resulted in axonal degeneration,
dopaminergic and motor neuron cell loss, and increased beta-synuclein expression.
We also observed that many of the identified, differentially expressed genes were
implicated in other brain disorders, which might explain the variable phenotypic
expression of pla2g6-associated disease, and found that top enriched canonical
pathways included those already known or suggested to play a major role in the
pathogenesis of Parkinson's disease. Our data support that pla2g6 is relevant for
cranial motor development with significant implications in the pathophysiology
underlying Parkinson's disease.
PMID- 29344928
TI - Morphine-Mediated Brain Region-Specific Astrocytosis Involves the ER Stress
Autophagy Axis.
AB - A recent study from our lab has revealed a link between morphine-mediated
autophagy and synaptic impairment. The current study was aimed at investigating
whether morphine-mediated activation of astrocytes involved the ER
stress/autophagy axis. Our in vitro findings demonstrated upregulation of GFAP
indicating astrocyte activation with a concomitant increase in the production of
proinflammatory cytokines in morphine-exposed human astrocytes. Using both
pharmacological and gene-silencing approaches, it was demonstrated that morphine
mediated defective autophagy involved upstream activation of ER stress with
subsequent downstream astrocyte activation via the MU-opioid receptor (MOR). In
vivo validation demonstrated preferential activation of ER stress/autophagy axis
in the areas of the brain not associated with pain such as the basal ganglia,
frontal cortex, occipital cortex, and the cerebellum of morphine-dependent rhesus
macaques, and this correlated with increased astrocyte activation and
neuroinflammation. Interventions aimed at blocking either the MOR or ER stress
could thus likely be developed as promising therapeutic targets for abrogating
morphine-mediated astrocytosis.
PMID- 29344930
TI - Maternal prenatal stress and infant DNA methylation: A systematic review.
AB - Maternal prenatal stress has been linked to a variety of infant postnatal
outcomes, partially through alterations in fetal HPA axis functioning; yet the
underlying pathobiology remains elusive. Current literature posits DNA
methylation as a candidate mechanism through which maternal prenatal stress can
influence fetal HPA axis functioning. The goal of this systematic review was to
summarize the literature examining the associations among maternal prenatal
stress, DNA methylation of commonly studied HPA axis candidate genes, and infant
HPA axis functioning. Results from the review provided evidence for a link
between various maternal prenatal stressors, NR3C1 methylation, and infant stress
reactivity, but findings among other genes were limited, with mixed results. An
original study quality review tool revealed that a majority of studies in the
review are adequate, and emphasizes the need for future research to consider
study quality when interpreting research findings.
PMID- 29344932
TI - Mothers' Early Mind-Mindedness Predicts Educational Attainment in Socially and
Economically Disadvantaged British Children.
AB - Relations between mothers' mind-mindedness (appropriate and nonattuned mind
related comments) at 8 months (N = 206), and children's educational attainment at
ages 7 (n = 158) and 11 (n = 156) were investigated in a British sample.
Appropriate mind-related comments were positively correlated with reading and
mathematics performance at both ages but only in the low-socioeconomic status
(SES) group. Path analyses showed that in the low-SES group, appropriate mind
related comments directly predicted age-11 reading performance, with age-4 verbal
ability mediating the relation between appropriate mind-related comments and age
7 reading. In contrast, maternal sensitivity and infant-mother attachment
security did not predict children's educational attainment. These findings are
discussed in terms of genetic and environmental contributions to reading and
mathematics performance.
PMID- 29344933
TI - Unexpected terrestrial hand posture diversity in wild mountain gorillas.
AB - OBJECTIVES: Gorillas, along with chimpanzees and bonobos, are ubiquitously
described as 'knuckle-walkers.' Consequently, knuckle-walking (KW) has been
featured pre-eminently in hypotheses of the pre-bipedal locomotor behavior of
hominins and in the evolution of locomotor behavior in apes. However, anecdotal
and behavioral accounts suggest that mountain gorillas may utilize a more complex
repertoire of hand postures, which could alter current interpretations of African
ape locomotion and its role in the emergence of human bipedalism. Here we
documented hand postures during terrestrial locomotion in wild mountain gorillas
to investigate the frequency with which KW and other hand postures are utilized
in the wild. MATERIALS AND METHODS: Multiple high-speed cameras were used to
record bouts of terrestrial locomotion of 77 habituated mountain gorillas at
Bwindi Impenetrable National Park (Uganda) and Volcanoes National Park (Rwanda).
RESULTS: We captured high-speed video of hand contacts in 8% of the world's
population of mountain gorillas. Our results reveal that nearly 40% of these
gorillas used "non-KW" hand postures, and these hand postures constituted 15% of
all hand contacts. Some of these "non-KW" hand postures have never been
documented in gorillas, yet match hand postures previously identified in
orangutans. DISCUSSION: These results highlight a previously unrecognized level
of hand postural diversity in gorillas, and perhaps great apes generally.
Although present at lower frequencies than KW, we suggest that the possession of
multiple, versatile hand postures present in wild mountain gorillas may represent
a shared feature of the African ape and human clade (or even great ape clade)
rather than KW per se.
PMID- 29344934
TI - Clinical impact of treatment delay in pancreatic cancer patients revisited.
PMID- 29344931
TI - Relationship between body mass, lean mass, fat mass, and limb bone cross
sectional geometry: Implications for estimating body mass and physique from the
skeleton.
AB - OBJECTIVES: Estimating body mass from skeletal dimensions is widely practiced,
but methods for estimating its components (lean and fat mass) are poorly
developed. The ability to estimate these characteristics would offer new insights
into the evolution of body composition and its variation relative to past and
present health. This study investigates the potential of long bone cross
sectional properties as predictors of body, lean, and fat mass. MATERIALS AND
METHODS: Humerus, femur and tibia midshaft cross-sectional properties were
measured by peripheral quantitative computed tomography in sample of young adult
women (n = 105) characterized by a range of activity levels. Body composition was
estimated from bioimpedance analysis. RESULTS: Lean mass correlated most strongly
with both upper and lower limb bone properties (r values up to 0.74), while fat
mass showed weak correlations (r <= 0.29). Estimation equations generated from
tibial midshaft properties indicated that lean mass could be estimated relatively
reliably, with some improvement using logged data and including bone length in
the models (minimum standard error of estimate = 8.9%). Body mass prediction was
less reliable and fat mass only poorly predicted (standard errors of estimate
>=11.9% and >33%, respectively). DISCUSSION: Lean mass can be predicted more
reliably than body mass from limb bone cross-sectional properties. The results
highlight the potential for studying evolutionary trends in lean mass from
skeletal remains, and have implications for understanding the relationship
between bone morphology and body mass or composition.
PMID- 29344935
TI - Progressive topological disorganization of brain network in focal epilepsy.
AB - OBJECTIVE: Increasing evidence has suggested that epilepsy is a network disease.
Graph theory is a mathematical tool that allows for the analysis and
quantification of the brain network. We aimed to evaluate the influences of
duration of epilepsy on the topological organization of brain network in focal
epilepsy patients with normal MRI using the graph theoretical analysis based on
diffusion tenor imaging. METHODS: We prospectively enrolled 66 patients with
focal epilepsy (18/66 patients were newly diagnosed) and 84 healthy subjects. All
of the patients with epilepsy had normal MRI on visual inspection. All of the
subjects underwent diffusion tensor imaging that was analyzed using graph theory
to obtain network measures. RESULTS: The measures of characteristic path length
and small-worldness in the patients with focal epilepsy were significantly
decreased, even after multiple corrections (P < .01). Moreover, the measures
including mean clustering coefficient and global efficiency in the patients with
epilepsy had strong tendency to decrease compared to those in healthy subjects (P
= .0153 and P = .0138, respectively). When comparing the measures among the
patients with newly diagnosed/chronic epilepsy and healthy subjects using ANOVA,
the characteristic path length (P = .006), small-worldness (P = .032), and global
efficiency (P = .004) were significantly different. In addition, the duration of
epilepsy was negatively correlated with global efficiency (r = -.249, P = .0454).
CONCLUSIONS: We newly found a progressive topological disorganization of the
brain network in focal epilepsy. In addition, we demonstrated disrupted
topological organization in focal epilepsy, shifting toward a more random state.
PMID- 29344936
TI - Author's reply to : Pancreatic cancer : Extension of tumor is associated with
timeliness of care and with survival in a population-based study.
PMID- 29344937
TI - NDUFAF3 variants that disrupt mitochondrial complex I assembly may associate with
cavitating leukoencephalopathy.
AB - Genetic abnormalities in mitochondrial complex assembling factors are associated
with leukoencephalopathy. We present a 1-year-old girl with consciousness
disturbance after a respiratory infection. Brain MRI revealed leukoencephalopathy
with bilaterally symmetrical hyperintensity in the substantia nigra, medial
thalamic nuclei, and basal nuclei, as well as cavities in the cerebral white
matter and corpus callosum. Lactate levels in the spinal fluid were high, while
magnetic resonance spectroscopy of the cerebral white matter and basal nuclei
showed high peak lactate levels, suggesting mitochondrial dysfunction. The
respiratory enzyme activity of complex I was reduced to 17% to 21% in skeletal
muscle. Whole exome sequencing identified compound heterozygous variations in
NDUFAF3, involved in the assembly of mitochondrial complex I
(c.342_343insGTG:p.117Valdup, c.505C > A:p.Pro169Thr). Two-dimensional, blue
native polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate-PAGE
revealed reductions in Q-module (NDUFS2, NDUFS3, and NDUFA9) and P-module
(NDUFB10 and NDUFB11) subunits, indicating disruption of mitochondrial complex I
assembly. Our report expands the spectrum of clinical phenotypes associated with
pathogenic variants of NDUFAF3.
PMID- 29344938
TI - A clinical audit on the efficacy and safety of uterine artery embolisation for
symptomatic adenomyosis: Results in 117 women.
AB - BACKGROUND: Uterine artery embolisation (UAE) is a possible uterine-sparing
treatment option for women with unsuccessful conservative management for
adenomyosis-related heavy menstrual bleeding (HMB) and dysmenorrhoea. AIM: To
conduct a clinical audit on the efficacy and safety of UAE for symptomatic
adenomyosis. MATERIALS AND METHODS: Retrospective review of 309 women who
underwent UAE identified 117 women with magnetic resonance imaging features of
adenomyosis (junctional zone thickness >= 12 mm). Overall success and HMB control
were rated by women. Visual analogue scale (VAS) pain score, Uterine Fibroid
Symptom and health-related Quality of Life (UFS-QoL) symptoms score and quality
of life score were also used to measure outcome. RESULTS: One hundred and fifteen
women (98%) were available for outcome evaluation. The mean follow-up was 22.5
months. Overall clinical success was achieved in 102/115 (89%) women; HMB control
was achieved in 91/104 (88%); dysmenorrhea relief was achieved in 94/104 (90%),
with VAS reduction of 6.13 (P < 0.001), Mean symptoms score was reduced from 58
to 17 at 12 months (P < 0.001) and QoL score increased from 42 to 88 at 12 months
(P < 0.001). Hysterectomy was performed on six (5%) women. There were three (3%)
mild groin haematomatas and three (3%) mild subacute complications (one possible
endometritis, two urinary tract infections; all responded to oral antibiotics).
Two women had unintended pregnancies which were complicated. CONCLUSIONS: In this
clinical audit UAE was found to be an effective uterine-sparing option for women
who had unsuccessful conservative treatments for adenomyosis-related HMB and
dysmenorrhoea. There were no major complications. Two women had unintended
pregnancies that were complicated.
PMID- 29344939
TI - Socially informed dispersal in a territorial cooperative breeder.
AB - Dispersal is a key process governing the dynamics of socially and spatially
structured populations and involves three distinct stages: emigration, transience
and settlement. At each stage, individuals have to make movement decisions, which
are influenced by social, environmental and individual factors. Yet, a
comprehensive understanding of the drivers that influence such decisions is still
lacking, particularly for the transient stage during which free-living
individuals are inherently difficult to follow. Social circumstances such as the
likelihood of encountering conspecifics can be expected to strongly affects
decision-making during dispersal, particularly in territorial species where
encounters with resident conspecifics are antagonistic. Here, we analysed the
movement trajectories of 47 dispersing coalitions of Kalahari meerkats Suricata
suricatta through a landscape occupied by constantly monitored resident groups,
while simultaneously taking into account environmental and individual
characteristics. We used GPS locations collected on resident groups to create a
georeferenced social landscape representing the likelihood of encountering
resident groups. We used a step-selection function to infer the effect of social,
environmental and individual covariates on habitat selection during dispersal.
Finally, we created a temporal mismatch between the social landscape and the
dispersal event of interest to identify the temporal scale at which dispersers
perceive the social landscape. Including information about the social landscape
considerably improved our representation of the dispersal trajectory compared to
analyses that only accounted for environmental variables. The latter were only
marginally selected or avoided by dispersers. Before leaving their natal
territory, dispersers selected areas frequently used by their natal group. In
contrast, after leaving their natal territory, they selectively used areas where
they were less likely to encounter unrelated groups. This pattern was
particularly marked in larger dispersing coalitions and when unrelated males were
part of the dispersing coalition. Our results suggest that, in socially and
spatially structured species, dispersers gather and process social information
during dispersal, and that reducing risk of aggression from unrelated resident
groups outweighs benefits derived from conspecific attraction. Finally, our work
underlines the intimate link between the social structure of a population and
dispersal, which affect each other reciprocally.
PMID- 29344940
TI - Obstetric and neonatal outcomes for women intending to use immersion in water for
labour and birth in Western Australia (2015-2016): A retrospective audit of
clinical outcomes.
AB - BACKGROUND: Research supports water immersion for labour if women are healthy,
with no obstetric or medical risk factors. AIMS: To evaluate the obstetric and
neonatal outcomes of women intending to use immersion in water for labour or
birth. METHODS: Retrospective audit of clinical outcomes for women intending to
labour or birth in water conducted between July 2015 and June 2016, at a tertiary
maternity hospital in Western Australia. Obstetric and neonatal data were
collected from medical records. Multivariable logistic regression was utilised to
investigate women who laboured in water stratified by those who birthed in water.
RESULTS: A total of 502 women intended to labour or birth in water; 199 (40%) did
not and 303 (60%) did. The majority of women using water immersion (179 of 303;
59%) birthed in water. Multiparous women were more likely than primparous to
birth in water (73% vs 46%; P < 0.001). Women who birthed in water were at
increased odds of: a first stage labour <=240 min (odds ratio (OR) 2.56, 95% CI
1.34-4.87, P = 0.004); a second stage <=60 min (OR 3.53, 95% CI 1.82-6.84, P <
0.000); a third stage labour of 11-30 min (OR 2.15, 95% CI 1.23-3.78, P = 0.008);
and having an intact perineum (OR 3.10, 95% CI 1.70-5.64, P < 0.000). CONCLUSION:
Not all women who set out to labour and birth in water achieve their aim. There
is a need for high-quality collaborative research into this option of labour and
birth, so women can make an informed choice around this birth option.
PMID- 29344941
TI - Systemic patterns of trabecular bone across the human and chimpanzee skeleton.
AB - Aspects of trabecular bone architecture are thought to reflect regional loading
of the skeleton, and thus differ between primate taxa with different locomotor
and postural modes. However, there are several systemic factors that affect bone
structure that could contribute to, or be the primary factor determining,
interspecific differences in bone structure. These systemic factors include
differences in genetic regulation, sensitivity to loading, hormone levels, diet,
and activity levels. Improved understanding of inter-/intraspecific variability,
and variability across the skeleton of an individual, is required to interpret
properly potential functional signals present within trabecular structure. Using
a whole-region method of analysis, we investigated trabecular structure
throughout the skeleton of humans and chimpanzees. Trabecular bone volume
fraction (BV/TV), degree of anisotropy (DA) and trabecular thickness (Tb.Th) were
quantified from high resolution micro-computed tomographic scans of the humeral
and femoral head, third metacarpal and third metatarsal head, distal tibia, talus
and first thoracic vertebra. We found that BV/TV is, in most anatomical sites,
significantly higher in chimpanzees than in humans, suggesting a systemic
difference in trabecular structure unrelated to local loading regime. Differences
in BV/TV between the forelimb and hindlimb did not clearly reflect differences in
locomotor loading in the study taxa. There were no clear systemic differences
between the taxa in DA and, as such, this parameter might reflect function and
relate to differences in joint loading. This systemic approach reveals both the
pattern of variability across the skeleton and between taxa, and helps identify
those features of trabecular structure that may relate to joint function.
PMID- 29344942
TI - Maternal care affects chicks' development differently according to sex in quail.
AB - Maternal behavior is known to influence the behavioral development of young.
Recently, it was demonstrated that maternal behavior also differed according to
sex chicks and brood sex composition. So, here, we explored if these factors
influenced behavioral development of chicks quail when they were brooded, and
what characteristics of chicks and foster females could best explain this
development. We studied three sets of chick pairs brooded by foster females:
unisex male, unisex female, and mixed broods. We found that both emotivity
profile and sociality depended on the sex: females were more reactive and less
social than males. Females' emotivity profile was correlated with brood
composition and foster female activity during maternal care. In males, only
sociality was correlated with foster females' scores of aggressive rejection. Our
results evidence that male and female chicks respond differentially to maternal
behavior. This is discussed in terms of ecological and physiological constraints
on development according to sex.
PMID- 29344943
TI - An exploratory analysis of the joint contribution of HPA axis activation and
motivation to early adolescent depressive symptoms.
AB - This study examines the interactive contribution of the hypothalamic-pituitary
adrenal (HPA) axis and approach-avoidance motivation systems to longitudinal
changes in depressive symptoms across the adolescent transition. In the summer
prior to, or fall of, 4th grade, 132 youth (68 girls; 64 boys; M age = 9.46
years) participated in a social challenge task and reported on their depressive
symptoms. In the winter of 6th grade, youth completed a semi-structured interview
of depression and a self-report measure of approach-avoidance motivations.
Analyses revealed two profiles of risk for adolescent depressive symptoms, with
some gender differences: (1) excessive disengagement, reflected in HPA
underactivation along with low approach motivation or high avoidance motivation;
and (2) excessive engagement, reflected in HPA overactivation along with high
approach motivation. This research highlights the importance of a multi-system
perspective on development, suggesting that the implications of HPA dysregulation
for depressive symptoms are contingent on adolescents' tendencies toward approach
versus avoidance.
PMID- 29344945
TI - Cumulative risk exposure moderates the association between parasympathetic
reactivity and inhibitory control in preschool-age children.
AB - A child's cumulative risk for early exposure to stress has been linked to
alterations of self-regulation outcomes, including neurobiological correlates of
inhibitory control (IC). We examined whether children's ability to engage the
parasympathetic nervous system impacts how risk affects IC. Children ages 3-5
years completed two laboratory measures of IC while respiratory sinus arrhythmia
(RSA) was measured, indexing parasympathetic activity. Children with greater risk
demonstrated lower IC; risk also moderated associations between RSA reactivity
and IC. For children with less risk, greater RSA withdrawal during IC tasks was
associated with better IC. In contrast, greater risk was associated with poor IC,
regardless of RSA withdrawal. Effects of risk were more pronounced for cumulative
than individual measures. Results suggest that cumulative risk exposure disrupts
connectivity between physiological and behavioral components of self-regulation
in early childhood. Parasympathetic withdrawal to cognitive tasks may be less
relevant for performance in developmental samples experiencing greater life
stress.
PMID- 29344944
TI - Early temperamental fearfulness and the developmental trajectory of error-related
brain activity.
AB - The error-related negativity (ERN) is a negative deflection in the event-related
potential waveform that occurs when an individual makes a mistake, and an
increased ERN has been proposed as a biomarker for anxiety. However, previous
work suggests that fearful children are characterized by a smaller ERN. We have
proposed that this may reflect the changing phenomenology of anxiety across
development. In the current study, we investigate this possibility using a
longitudinal within-subject design. In 271 children, we completed observational
measures of fear when the children were 3 years old, and then measured the ERN
when the children were 6 and 9 years old. Fearful children were characterized by
a decreased ERN when they were 6-year-old; by age 9, the same children who were
fearful at age 3 had increased ERNs-a pattern that closely resembles that of
anxious adolescents and adults.
PMID- 29344946
TI - Preeclampsia and scleroderma: a prospective nationwide analysis.
AB - INTRODUCTION: In a preliminary case-control study, women with scleroderma more
frequently reported having had hypertensive complications during pregnancy
compared with healthy women. MATERIAL AND METHODS: To prospectively investigate
this possible association, we conducted a nation-wide cohort analysis of a major
hypertensive complication during pregnancy, namely preeclampsia, and later
scleroderma. Analyses were based on Danish register-based birth and hospital
contact data on preeclampsia and scleroderma. We followed 778,758 women from time
of giving birth between 1978 and 2010 to end of follow-up, emigration, death, or
scleroderma diagnosis, whichever occurred first. The association was evaluated by
incidence rate ratios, obtained in Poisson regression models. RESULTS: We report
that preeclampsia is associated with a 69% significantly increased risk of later
developing scleroderma. CONCLUSIONS: Though these findings do not impact clinical
care directly, the association of preeclampsia with scleroderma underscores the
significant relation of preeclampsia and other adverse pregnancy outcomes with
later disease in women and should be included in patient counseling and
education.
PMID- 29344947
TI - Genome-wide population structure and admixture analysis reveals weak
differentiation among Ugandan goat breeds.
AB - Uganda has a large population of goats, predominantly from indigenous breeds
reared in diverse production systems, whose existence is threatened by
crossbreeding with exotic Boer goats. Knowledge about the genetic characteristics
and relationships among these Ugandan goat breeds and the potential admixture
with Boer goats is still limited. Using a medium-density single nucleotide
polymorphism (SNP) panel, we assessed the genetic diversity, population structure
and admixture in six goat breeds in Uganda: Boer, Karamojong, Kigezi, Mubende,
Small East African and Sebei. All the animals had genotypes for about 46 105 SNPs
after quality control. We found high proportions of polymorphic SNPs ranging from
0.885 (Kigezi) to 0.928 (Sebei). The overall mean observed (HO ) and expected (HE
) heterozygosity across breeds was 0.355 +/- 0.147 and 0.384 +/- 0.143
respectively. Principal components, genetic distances and admixture analyses
revealed weak population sub-structuring among the breeds. Principal components
separated Kigezi and weakly Small East African from other indigenous goats. Sebei
and Karamojong were tightly entangled together, whereas Mubende occupied a more
central position with high admixture from all other local breeds. The Boer breed
showed a unique cluster from the Ugandan indigenous goat breeds. The results
reflect common ancestry but also some level of geographical differentiation.
admixture and f4 statistics revealed gene flow from Boer and varying levels of
genetic admixture among the breeds. Generally, moderate to high levels of genetic
variability were observed. Our findings provide useful insights into maintaining
genetic diversity and designing appropriate breeding programs to exploit within
breed diversity and heterozygote advantage in crossbreeding schemes.
PMID- 29344948
TI - Glycation of ovalbumin after high-intensity ultrasound pretreatment: effects on
conformation, immunoglobulin (Ig)G/IgE binding ability and antioxidant activity.
AB - BACKGROUND: Ovalbumin (OVA), a protein with excellent nutritional and processing
properties, is the major allergen of hen egg white. High-intensity ultrasound
treatment increases the immunoglobulin (Ig)G and IgE binding abilities by
unfolding the conformational structure of OVA. This may allow a modification of
the IgG and IgE binding of OVA by combining high-intensity ultrasound with other
methods, such as glycation, thus representing a promising method for the
improvement of protein properties. RESULTS: Glycation with mannose (M) after
ultrasound pretreatment at 0-600 W significantly reduced the IgG and IgE binding
abilities and dramatically enhanced the antioxidant activity of OVA-M conjugates,
with the lowest values of IgG and IgE binding and highest values of antioxidant
capacity observed at 600 W. Polyacrylamide gel electrophoresis showed that the
molecular weight of OVA-M conjugates with ultrasound pretreatment increased more
than non-pretreatment sample, implying that ultrasound pretreatment promoted
glycation. The alpha-helix content and ultraviolet absorption of OVA were
observably increased, whereas beta-sheet content, intrinsic fluorescence and
surface hydrophobicity were notably decreased, indicating that the tertiary and
secondary structures of OVA were markedly changed. CONCLUSION: High-intensity
ultrasound pretreatment can be conducive to reducing the binding abilities of IgG
and IgE and enhancing the antioxidant activity of OVA-M conjugates. Therefore,
glycation combined with high-intensity ultrasound pretreatment might be a
promising method for producing hypo-allergenic and high-antioxidant OVA products.
(c) 2018 Society of Chemical Industry.
PMID- 29344949
TI - Flavour-active compounds in thermally treated yeast extracts.
AB - BACKGROUND: Aroma-active compounds and non-volatile substances determine the
characteristic aroma and taste of yeast extract (YE). Changes in the
characteristic aroma and taste of YE due to thermal reaction are rarely studied,
and the relationship between aroma-active compounds and non-volatile compounds is
not yet clear. RESULTS: Non-volatile compounds identified by HPLC and LC/MS/MS
were reduced by a rise in temperature, except for some amino acids. Peptides
underwent degradation. In addition, a further rise in temperature above 120
degrees C resulted in a bitter and sour taste. Furans, pyrazines, thiophenes,
thiazoles and some branched chain sulfur compounds were derived from GC/O/MS
(SPME and SAFE). Sensory results revealed that the concentration of volatile
compounds increased with an increase in temperature. The overall aroma profiles
of YE at 25, 100 and 110 degrees C were buttery, green, nutty and meaty, while
YE at 140 degrees C had a strong sour and sulfur odour. CONCLUSION: The non
volatile compounds of YE were reduced and different volatile compounds were
produced under different thermal treatments. There was a negative correlation
between these two types of compounds. The different taste sensors and all
precursors were correlated with each other. There are significant relationships
between different odorants and aroma-active compounds of YE after thermal
treatment. (c) 2018 Society of Chemical Industry.
PMID- 29344950
TI - Systematic review and meta-analysis of left ventricular endocardial pacing in
advanced heart failure: Clinically efficacious but at what cost?
AB - INTRODUCTION: Cardiac resynchronization using a left ventricular (LV) epicardial
lead placed in the coronary sinus is now routinely used in the management of
heart failure patients. LV endocardial pacing is an alternative when this is not
feasible, with outcomes data sparse. OBJECTIVE: To review the available evidence
on the efficacy and safety of endocardial LV pacing via meta-analysis. METHODS:
EMBASE, MEDLINE, and COCHRANE databases with the search term "endocardial
biventricular pacing" or "endocardial cardiac resynchronization" or "left
ventricular endocardial" or "endocardial left ventricular." Comparisons of pre
and post-QRS width, LV ejection fraction (LVEF), and New York Heart Association
(NYHA) functional classification was performed, and mean differences (and
respective 95% confidence interval [CI]) applied as a measurement of treatment
effect. RESULTS: Fifteen studies, including 362 patients, were selected. During a
mean follow-up of 40 +/- 24.5 months, death occurred in 72 patients (11 per 100
patient-years). Significant improvements in LVEF (mean difference 7.9%, 95% CI 5
10%, P < 0.0001; I2 = 73%), QRS width (mean difference: -41% 95% -75 to -7%; P <
0.0001; I2 = 94%), and NYHA class (mean difference: -1.06, 95% CI -1.2 to -0.9,
P < 0.0001; I2 = 60%), (all P < 0.0001) occurred. Stroke rate was 3.3-4.2 per
100 patient-years, which is higher than equivalent heart failure trial
populations and recent meta-analysis that included small case series. CONCLUSION:
LV endocardial lead implantation is a potentially efficacious alternative to CS
lead placement, but preliminary data suggest a potentially higher risk of stroke
during follow-up when compared to the expected incidence of stroke in similar
cohorts of patients.
PMID- 29344951
TI - The rise of a novel classification system for endometrial carcinoma; integration
of molecular subclasses.
AB - Endometrial cancer is a clinically heterogeneous disease and it is becoming
increasingly clear that this heterogeneity may be a function of the diversity of
the underlying molecular alterations. Recent large-scale genomic studies have
revealed that endometrial cancer can be divided into at least four distinct
molecular subtypes, with well-described underlying genomic aberrations. These
subtypes can be reliably delineated and carry significant prognostic as well as
predictive information; embracing and incorporating them into clinical practice
is thus attractive. The road towards the integration of molecular features into
current classification systems is not without obstacles. Collaborative studies
engaging research teams from across the world are working to define pragmatic
assays, improve risk stratification systems by combining molecular features and
traditional clinicopathological parameters, and determine how molecular
classification can be optimally utilized to direct patient care. Pathologists and
clinicians caring for women with endometrial cancer need to engage with and
understand the possibilities and limitations of this new approach, because
integration of molecular classification of endometrial cancers is anticipated to
become an essential part of gynaecological pathology practice. This review will
describe the challenges in current systems of endometrial carcinoma
classification, the evolution of new molecular technologies that define
prognostically distinct molecular subtypes, and potential applications of
molecular classification as a step towards precision medicine and refining care
for individuals with the most common gynaecological cancer in the developed
world. Copyright (c) 2018 Pathological Society of Great Britain and Ireland.
Published by John Wiley & Sons, Ltd.
PMID- 29344952
TI - A Weaning Protocol for Venovenous Extracorporeal Membrane Oxygenation With a
Review of the Literature.
AB - Several articles have discussed the weaning process for venoarterial
extracorporeal membrane oxygenation; however, there is no published report to
outline a standardized approach for weaning a patient from venovenous
extracorporeal membrane oxygenation (ECMO). This complex process requires an
organized approach and a thorough understanding of ventilator management and ECMO
physiology. The purpose of this article is to describe the venovenous ECMO
weaning protocol used at our institution as well as provide a review of the
literature.
PMID- 29344953
TI - Established, emerging and elusive molecular targets in the treatment of lung
cancer.
AB - Although histological subtype still underlies tumour classification and
treatment, the recognition that lung cancer is, largely, a genetic disease has
prompted a push to reconfigure cancer taxonomies according to molecular criteria.
In this review, we discuss established (e.g. EGFR, ALK, ROS1, and programmed cell
death 1/programmed death-ligand 1), emerging (e.g. MET, RET, and NTRK) and
elusive (e.g. TP53, KRAS, and MYC) molecular targets in the treatment of lung
cancer. We synthesize a large and rapidly growing body of literature regarding
the discovery and therapeutic inhibition of these targets in lung cancer.
Copyright (c) 2018 Pathological Society of Great Britain and Ireland. Published
by John Wiley & Sons, Ltd.
PMID- 29344955
TI - Development of an advanced two-dimensional microdosimetric detector based on
THick Gas Electron Multipliers.
AB - PURPOSE: The THick Gas Electron Multiplier (THGEM)-based tissue-equivalent
proportional counter (TEPC) has been proven to be useful for microdosimetry due
to its flexibility in varying the gaseous sensitive volume and achieving high
multiplication gain. Aiming at measuring the spatial distribution of radiation
dose for mixed neutron-gamma fields, an advanced two-dimensional (2D) THGEM-TEPC
was designed and constructed at McMaster University which will enable us to
overcome the operational limitation of the classical TEPCs, particularly for high
dose rate fields. Compared to the traditional TEPCs, anode wire electrodes were
replaced by a THGEM layer, which not only enhances the gas multiplication gain
but also offers a flexible and convenient fabrication for building 2D detectors.
METHOD & MATERIALS: The 2D THGEM TEPC consists of an array of 3 * 3 sensitive
volumes, equivalent to nine individual TEPCs, each of which has a dimension of 5
mm diameter and length. Taking the overall cost, size and flexibility into
account, to process nine detector signals simultaneously, a multi-input digital
pulse processing system was developed by using modern microcontrollers, each of
which is coupled with a 12-bit sampling ADC. RESULTS: Using the McMaster
Tandetron 7 Li(p,n) accelerator neutron source, both fundamental detector
performance, as well as neutron dosimetric response of the 2D THGEM-TEPC, has
been extensively investigated and compared to the data acquired by a standard
spherical TEPC. It was shown that the microdosimetric response and the measured
absorbed dose rate of the 2D THGEM detector developed in this study are
comparable to the standard 1/2" TEPC which is commercially available. CONCLUSION:
This study proved that the 2D TEPC based on the THGEM technology can be
effectively used in microdosimetry studies and is a promising detector for
measuring the absorbed dose rate distribution over an area in mixed radiation
fields. This unique small gas cavity detector opens new possibilities in
applications for high-intensity mixed radiation fields as well as in
nanodosimetry.
PMID- 29344954
TI - Mixed ductal-lobular carcinomas: evidence for progression from ductal to lobular
morphology.
AB - Mixed ductal-lobular carcinomas (MDLs) show both ductal and lobular morphology,
and constitute an archetypal example of intratumoural morphological
heterogeneity. The mechanisms underlying the coexistence of these different
morphological entities are poorly understood, although theories include that
these components either represent 'collision' of independent tumours or evolve
from a common ancestor. We performed comprehensive clinicopathological analysis
of a cohort of 82 MDLs, and found that: (1) MDLs more frequently coexist with
ductal carcinoma in situ (DCIS) than with lobular carcinoma in situ (LCIS); (2)
the E-cadherin-catenin complex was normal in the ductal component in 77.6% of
tumours; and (3) in the lobular component, E-cadherin was almost always
aberrantly located in the cytoplasm, in contrast to invasive lobular carcinoma
(ILC), where E-cadherin is typically absent. Comparative genomic hybridization
and multiregion whole exome sequencing of four representative cases revealed that
all morphologically distinct components within an individual case were clonally
related. The mutations identified varied between cases; those associated with a
common clonal ancestry included BRCA2, TBX3, and TP53, whereas those associated
with clonal divergence included CDH1 and ESR1. Together, these data support a
model in which separate morphological components of MDLs arise from a common
ancestor, and lobular morphology can arise via a ductal pathway of tumour
progression. In MDLs that present with LCIS and DCIS, the clonal divergence
probably occurs early, and is frequently associated with complete loss of E
cadherin expression, as in ILC, whereas, in the majority of MDLs, which present
with DCIS but not LCIS, direct clonal divergence from the ductal to the lobular
phenotype occurs late in tumour evolution, and is associated with aberrant
expression of E-cadherin. The mechanisms driving the phenotypic change may
involve E-cadherin-catenin complex deregulation, but are yet to be fully
elucidated, as there is significant intertumoural heterogeneity, and each case
may have a unique molecular mechanism. (c) 2018 The Authors. The Journal of
Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of
Great Britain and Ireland.
PMID- 29344956
TI - Dispersal capacity of Haematopota spp. and Stomoxys calcitrans using a mark
release-recapture approach in Belgium.
AB - The dispersion potential of mechanical vectors is an important factor in the
dissemination of pathogens. A mark-release-recapture experiment was implemented
using two groups (unfed and partially fed) of the Tabanidae (Diptera)
(Haematopota spp.) and biting Muscidae (Diptera) (Stomoxys calcitrans) most
frequently collected in Belgium in order to evaluate their dispersion potential.
In total, 2104 specimens of Haematopota spp. were collected directly from horses
and 5396 S. calcitrans were collected in a cattle farm using hand-nets. Some of
these insects were partially fed in vitro and all were subsequently coloured.
Overall, 67 specimens of S. calcitrans (1.2%) and 17 of Haematopota spp. (0.8%)
were recaptured directly on horses. Stomoxys calcitrans flew maximum distances of
150 m and 300 m when partially fed and unfed, respectively. Haematopota spp.
travelled maximum distances of 100 m and 200 m when partially fed and unfed,
respectively. Segregation measures seem essential in order to reduce the risk for
pathogen transmission. A distance of 150 m appears to be the minimum required for
segregation to avoid the risk for mechanical transmission, but in areas of higher
vector density, this should probably be increased.
PMID- 29344957
TI - Rapid differentiation of Chinese hop varieties (Humulus lupulus) using volatile
fingerprinting by HS-SPME-GC-MS combined with multivariate statistical analysis.
AB - BACKGROUND: Hops impart flavor to beer, with the volatile components
characterizing the various hop varieties and qualities. Fingerprinting,
especially flavor fingerprinting, is often used to identify 'flavor products'
because inconsistencies in the description of flavor may lead to an incorrect
definition of beer quality. Compared to flavor fingerprinting, volatile
fingerprinting is simpler and easier. RESULTS: We performed volatile
fingerprinting using head space-solid phase micro-extraction gas chromatography
mass spectrometry combined with similarity analysis and principal component
analysis (PCA) for evaluating and distinguishing between three major Chinese
hops. Eighty-four volatiles were identified, which were classified into seven
categories. Volatile fingerprinting based on similarity analysis did not yield
any obvious result. By contrast, hop varieties and qualities were identified
using volatile fingerprinting based on PCA. The potential variables explained the
variance in the three hop varieties. In addition, the dendrogram and principal
component score plot described the differences and classifications of hops.
CONCLUSION: Volatile fingerprinting plus multivariate statistical analysis can
rapidly differentiate between the different varieties and qualities of the three
major Chinese hops. Furthermore, this method can be used as a reference in other
fields. (c) 2018 Society of Chemical Industry.
PMID- 29344958
TI - Protective effects of new antioxidant compositions of 4-methylcoumarins and
related compounds with dl-alpha-tocopherol and l-ascorbic acid.
AB - BACKGROUND: Coumarin derivatives possess a wide range of biological activities.
By functionalization of the parent coumarin skeleton that has neither antioxidant
nor biological activity, a series of new bio-antioxidants has been designed.
RESULTS: New antioxidant compositions (equimolar binary and ternary mixtures) of
eight 4-methylcoumarins and three related compounds have been tested and
different effects between individual components have been observed: synergism
(positive effect), additivism (summary effect) and antagonism (negative effect).
Higher oxidative stability of the lipid substrate was obtained in the presence of
the new antioxidant compositions of the studied compounds with dl-alpha
tocopherol and l-ascorbic acid. The role of each component in the antioxidant
compositions of ternary mixtures has been identified by using new equations
composed by the authors. CONCLUSION: All ternary mixtures demonstrate synergism
as a result of continuous regeneration of dl-alpha-tocopherol from the studied
antioxidants and l-ascorbic acid. Theoretical calculations have been probed as
indicators of the expected effects between the individual components in a binary
mixture. (c) 2018 Society of Chemical Industry.
PMID- 29344959
TI - Three gene phylogeny of the Thoreales (Rhodophyta) reveals high species
diversity.
AB - The freshwater red algal order Thoreales has triphasic life history composed of a
diminutive diploid "Chantransia" stage, a distinctive macroscopic gametophyte
with multi-axial growth and carposporophytes that develop on the gametophyte
thallus. This order is comprised of two genera, Thorea and Nemalionopsis. Thorea
has been widely reported with numerous species, whereas Nemalionopsis has been
more rarely observed with only a few species described. DNA sequences from three
loci (rbcL, cox1, and LSU) were used to examine the phylogenetic affinity of
specimens collected from geographically distant locations including North
America, South America, Europe, Pacific Islands, Southeast Asia, China, and
India. Sixteen species of Thorea and two species of Nemalionopsis were
recognized. Morphological observations confirmed the distinctness of the two
genera and also provided some characters to distinguish species. However, many of
the collections were in "Chantransia" stage rather than gametophyte stage,
meaning that key diagnostic morphological characters were unavailable. Three new
species are proposed primarily based on the DNA sequence data generated in this
study, Thorea kokosinga-pueschelii, T. mauitukitukii, and T. quisqueyana. In
addition to these newly described species, one DNA sequence from GenBank was not
closely associated with other Thorea clades and may represent further diversity
in the genus. Two species in Nemalionopsis are recognized, N. shawii and N.
parkeri nom. et stat. nov. Thorea harbors more diversity than had been recognized
by morphological data alone. Distribution data indicated that Nemalionopsis is
common in the Pacific region, whereas Thorea is more globally distributed. Most
species of Thorea have a regional distribution, but Thorea hispida appears to be
cosmopolitan.
PMID- 29344960
TI - Association of genetic variation in telomere-related SNP and telomerase with
ventricular arrhythmias in ischemic cardiomyopathy.
AB - BACKGROUND: Telomeres are known to provide genomic stability and telomere length
has been associated with cardiovascular diseases. Moreover, a higher telomerase
activity has been shown to be associated with ventricular arrhythmias (VA) in
ischemic cardiomyopathy. Increasing evidence suggests that genetic variation in
key telomere genes has an impact on telomerase activity. Each copy of the minor
allele of SNP rs12696304, at a locus including TERC (telomerase), has been
associated with ~75 base pairs reduction in mean telomere length likely mediated
by an effect on TERC expression. We investigated the impact of genetic variation
of this SNP on telomerase and its association with VA in ischemic cardiomyopathy
patients. METHODS AND RESULTS: Ninety ischemic cardiomyopathy patients with
primary prevention implantable cardioverter defibrillators (ICDs) were recruited.
Thirty-five received appropriate ICD therapy for potentially fatal VA (cases),
while the remaining 55 patients did not (controls). No significant differences in
baseline demographics were seen between the groups. TS was measured by qPCR,
telomerase activity by TRAP assay, and SNP genotyping with Taqman probes.
Telomerase was highest in C homozygous allele and had a significant association
with VA in this group only (C/C,C/G,G/G; P-value 0.04, 0.33, 0.43). CONCLUSION:
The present study is the first to examine the association between telomerase, a
SNP at a locus including TERC, and VA in ischemic cardiomyopathy patients.
Homozygosity for C-allele significantly effects telomerase expression and its
association with VA in this cohort. Large-scale prospective studies are required
to determine if this genetic variation predisposes patients to greater arrhythmic
tendency post-MI.
PMID- 29344961
TI - In vivo evaluation of some biophysical parameters of the facial skin of Indian
subjects living in Mumbai. Part II: Variability with age and gender.
AB - BACKGROUND: A previously published work explored the diversity of some
biophysical parameters (colour, elasticity, sebum production, skin microrelief,
etc.) of the skin of 1204 Indian women, differently aged, living in four Indian
cities (Chennai, Delhi, Kolkata and Mumbai). The present work aimed at completing
such research by focusing on possible gender-related differences in the same skin
parameters, between Indian men and women living in the same Indian city (Mumbai).
METHODS: A total of 297 Indian men, differently aged (18-70y), were recruited in
Mumbai, completing the panel of 303 women who were previously recruited in this
same city. The same instrumental measurements of facial skin colour and its
homogeneity, its mechanical properties, the sebum production, skin pores size,
skin relief, etc. as in the previous work, were conducted. RESULTS: Overall, the
facial skin colour shows a darker complexion in men as compared to women, on
forehead, ocular region, lips, chin and cheek. The skin colour unevenness, which
increases with age, was found higher in men, as compared to women. At comparable
age, women and men present a same density of skin pores, whereas those of men
appear larger, up to 55y. The deepness of Crow's feet wrinkles does not
significantly differ between genders. A lesser extensibility was found on the
cheeks of men. In men, the sebum production was found significantly higher than
that of women at ages above 40y. CONCLUSIONS: This work indicates some commonly
shared age-related skin features between women and men from Mumbai, despite
slight different characteristics such as skin pigmentation, forehead/cheek colour
contrast, mechanical properties and sebum production.
PMID- 29344962
TI - Bridging the molecular divide: alcohol-induced downregulation of PAX9 and tumour
development.
AB - The pathogenesis of oro-oesophaeal squamous cell carcinoma is causally linked to
the consumption of alcohol. Beyond the carcinogenic effects of ethanol and its
metabolites via DNA damage, the precise mechanisms by which alcohol drives
tumourigenesis remain to be fully elucidated. A novel contributor now revealed is
aberrant differentiation and proliferation mediated by suppression of PAX9, a key
regulator of normal squamous maturation in oro-oesophageal tissues. Copyright (c)
2018 Pathological Society of Great Britain and Ireland. Published by John Wiley &
Sons, Ltd.
PMID- 29344963
TI - Refractory Pulmonary Edema and Upper Body Hypoxemia During Veno-Arterial
Extracorporeal Membrane Oxygenation-A Case for Atrial Septostomy.
AB - Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) provides mechanical
circulatory support for patients with advanced cardiogenic shock, facilitating
myocardial recovery and limiting multi-organ failure. In patients with severely
limited left ventricular ejection, peripheral VA-ECMO can further increase left
ventricular and left atrial pressures (LAP). Failure to decompress the left heart
under these circumstances can result in pulmonary edema and upper body hypoxemia,
that is, myocardial and cerebral ischemia. Atrial septostomy can decrease LAP in
these situations. However, the effects of atrial septostomy on upper body
oxygenation remain unknown. After IRB approval, we identified 9 out of 242 adult
VA-ECMO patients between January 2011 and June 2016 who also underwent atrial
septostomy for refractory pulmonary edema/upper body hypoxemia. We analyzed
LAP/pulmonary capillary wedge pressure (PCWP), right atrial pressures (RAPs), Pa
O2 /Fi O2 ratios (blood samples from right radial artery), intrathoracic volume
status, and resolution of pulmonary edema before and up to 48 h after septostomy.
There were no procedure-related complications. Thirty-day survival was 44%.
LAP/PCWP decreased by approximately 40% immediately following septostomy and
remained so for at least 24 h. Pa O2 /Fi O2 ratios significantly increased from
0.49 (0.38-2.12) before to 5.35 (3.01-7.69) immediately after septostomy and
continued so for 24 h, 6.6 (4.49-10.93). Radiographic measurements also indicated
a significant improvement in thoracic intravascular volume status after atrial
septostomy. Atrial septostomy reduces LAP and improves upper body oxygenation and
intrathoracic vascular volume status in patients developing severe refractory
pulmonary edema while undergoing peripheral VA-ECMO. Atrial septostomy therefore
appears safe and suitable to reduce the risk of upper body ischemia under these
circumstances.
PMID- 29344964
TI - Recent advances and opportunities in proteomic analyses of tumour heterogeneity.
AB - Solid tumour malignancies comprise a highly variable admixture of tumour and non
tumour cellular populations, forming a complex cellular ecosystem and tumour
microenvironment. This tumour heterogeneity is not incidental, and is known to
correlate with poor patient prognosis for many cancer types. Indeed, non
malignant cell populations, such as vascular endothelial and immune cells, are
known to play key roles supporting and, in some cases, driving aggressive tumour
biology, and represent targets of emerging therapeutics, such as antiangiogenesis
and immune checkpoint inhibitors. The biochemical interplay between these
cellular populations and how they contribute to molecular tumour heterogeneity
remains enigmatic, particularly from the perspective of the tumour proteome. This
review focuses on recent advances in proteomic methods, namely imaging mass
spectrometry, single-cell proteomic techniques, and preanalytical sample
processing, that are uniquely positioned to enable detailed analysis of discrete
cellular populations within tumours to improve our understanding of tumour
proteomic heterogeneity. This review further emphasizes the opportunity afforded
by the application of these techniques to the analysis of tumour heterogeneity in
formalin-fixed paraffin-embedded archival tumour tissues, as these represent an
invaluable resource for retrospective analyses that is now routinely accessible,
owing to recent technological and methodological advances in tumour tissue
proteomics. Copyright (c) 2018 Pathological Society of Great Britain and Ireland.
Published by John Wiley & Sons, Ltd.
PMID- 29344965
TI - Occupational therapy publications by Australian authors: A bibliometric analysis.
AB - BACKGROUND: Bibliometrics refers to the collection and measurement of publishing
and citation data configurations with the goal of quantifying the influence of
scholarly activities. Advantages of bibliometrics include the generation of
quantitative indicators of impact, productivity, quality and collaboration. Those
parties who benefit from the results of bibliometric analysis include
researchers, educators, journal publishers, employers and research funding
bodies. METHODS: A bibliometric analysis was completed of peer-reviewed
literature from 1991 to 2015, written by Australian occupational therapists (who
were able to be identified as such), and indexed in the Science Citation Index
Expanded (SCI-Expanded) or the Social Sciences Citation Index (SSCI) databases.
"Occupational therapy" and "occupational therapist(s)" were used as keywords to
search journal articles' publication title, abstract, author details, keywords
and KeyWord Plus. RESULTS: Between 1991 and 2015, 752 peer-reviewed journal
articles were published by Australian occupational therapy authors. On average,
those articles had 3.7 authors, 35 references, and were nine pages in length. The
top four journals in which Australian occupational therapists published were
Australian Occupational Therapy Journal, British Journal of Occupational Therapy,
American Journal of Occupational Therapy, and Physical and Occupational Therapy
in Paediatrics. The four Australian institutions that generated the largest
number of occupational therapy articles were the University of Queensland,
University of Sydney, La Trobe University, and Monash University. The top four
countries with whom Australian authors collaborated in manuscript writing were
the United Kingdom, United States, Canada and Sweden. CONCLUSION: The volume of
occupational therapy peer-reviewed literature has grown over the last two
decades. Australian authors have and continue to make significant contributions
to the occupational therapy body of knowledge nationally and internationally.
PMID- 29344966
TI - Quorum-sensing molecule dihydroxy-2,3-pentanedione and its analogs as regulators
of epithelial integrity.
AB - BACKGROUND AND OBJECTIVE: Quorum-sensing molecules regulate the behavior of
bacteria within biofilms and at the same time elicit an immune response in host
tissues. Our aim was to investigate the regulatory role of dihydroxy-2,3
pentanedione (DPD), the precursor of universal autoinducer-2 (AI-2), and its
analogs (ethyl-DPD, butyl-DPD and isobutyl-DPD) in the integrity of gingival
epithelial cells. MATERIAL AND METHODS: Human gingival keratinocytes were
incubated with four concentrations (10 MUmol L-1 , 1 MUmol L-1 , 100 nmol L-1 and
10 nmol L-1 ) of DPD and its analogs for 24 hours. The numbers of viable cells
were determined using a proliferation kit, matrix metalloproteinase (MMP)-2 and
9 activities were determined by gelatin zymography, and expression of occludin
protein and occludin mRNA were determined by western blotting and RT-qPCR,
respectively. RESULTS: Increased cell proliferation was observed in gingival
keratinocytes incubated with 100 nmol L-1 of butyl-DPD. MMP-9 activity was
elevated in cells incubated with 10 MUmol L-1 of ethyl-DPD. On the other hand,
MMP-2 activity did not show any significant change when gingival keratinocytes
were incubated with or without DPD or analogs. Western blot analyses demonstrated
five forms (105, 61, 52.2, 44 and 37 kDa) of occludin. Incubation with 1 MUmol L
1 and 100 nmol L-1 of DPD and with 10 nmol L-1 of ethyl-DPD increased dimeric
(105 kDa) forms of occludin, while incubation with 100 nmol L-1 of isobutyl-DPD
increased monomeric (61 kDa) forms. DPD and ethyl-DPD decreased, and 100 nmol L-1
of isobutyl-DPD and 10 nmol L-1 of butyl-DPD increased, the monomeric (52.2 kDa
and 44 kDa) forms of occludin, whereas ethyl-DPD decreased and isobutyl-DPD
increased, the low-molecular-weight (37 kDa) forms. According to RT-qPCR
analysis, the exposure of gingival keratinocytes to 10 MUmol L-1 of isobutyl-DPD
up-regulated expression of occludin. CONCLUSION: The results indicate that
isobutyl-DPD has the potential to enhance the integrity of the epithelium by
stimulating the formation of occluding, without affecting the proliferation or
gelatinolytic enzyme activities of the exposed cells. The modulatory effect of an
AI-2 analog on the epithelial cell response is shown for the first time.
PMID- 29344967
TI - Predictive neuromechanical simulations indicate why walking performance declines
with ageing.
AB - KEY POINTS: Although the natural decline in walking performance with ageing
affects the quality of life of a growing elderly population, its physiological
origins remain unknown. By using predictive neuromechanical simulations of human
walking with age-related neuro-musculo-skeletal changes, we find evidence that
the loss of muscle strength and muscle contraction speed dominantly contribute to
the reduced walking economy and speed. The findings imply that focusing on
recovering these muscular changes may be the only effective way to improve
performance in elderly walking. More generally, the work is of interest for
investigating the physiological causes of altered gait due to age, injury and
disorders. ABSTRACT: Healthy elderly people walk slower and energetically less
efficiently than young adults. This decline in walking performance lowers the
quality of life for a growing ageing population, and understanding its
physiological origin is critical for devising interventions that can delay or
revert it. However, the origin of the decline in walking performance remains
unknown, as ageing produces a range of physiological changes whose individual
effects on gait are difficult to separate in experiments with human subjects.
Here we use a predictive neuromechanical model to separately address the effects
of common age-related changes to the skeletal, muscular and nervous systems. We
find in computer simulations of this model that the combined changes produce gait
consistent with elderly walking and that mainly the loss of muscle strength and
mass reduces energy efficiency. In addition, we find that the slower preferred
walking speed of elderly people emerges in the simulations when adapting to
muscle fatigue, again mainly caused by muscle-related changes. The results
suggest that a focus on recovering these muscular changes may be the only
effective way to improve performance in elderly walking.
PMID- 29344968
TI - A novel nested polymerase chain reaction assay targeting Plasmodium mitochondrial
DNA in field-collected Anopheles mosquitoes.
AB - Sensitive techniques for the detection of Plasmodium (Aconoidasida: Plasmodiidae)
sporozoites in field-collected malaria vectors are essential for the correct
assessment of risk for malaria transmission. A real-time polymerase chain
reaction (RT-PCR) protocol targeting Plasmodium mtDNA proved to be much more
sensitive in detecting sporozoites in mosquitoes than the widely used enzyme
linked immunosorbent assay targeting Plasmodium circumsporozoite protein (CSP
ELISA). However, because of the relatively high costs associated with equipment
and reagents, RT-PCRs are mostly used to assess the outcomes of experimental
infections in the frame of research experiments, rather than in routine
monitoring of mosquito infection in the field. The present authors developed a
novel mtDNA-based nested PCR protocol, modified from a loop-mediated isothermal
amplification (LAMP) assay for Plasmodium recognition in human blood samples, and
compared its performance with that of routinely used CSP-ELISAs in field
collected Anopheles coluzzii (Diptera: Culicidae) samples. The nested PCR showed
1.4-fold higher sensitivity than the CSP-ELISA. However, nested PCR results
obtained in two laboratories and in different replicates within the same
laboratory were not 100% consistent, probably because the copy number of
amplifiable Plasmodium mtDNA was close in some specimens to the threshold of
nested PCR sensitivity. This implies that Plasmodium-positive specimens should be
confirmed by a second nested PCR to avoid false positives. Overall, the results
emphasize the need to use molecular approaches to obtain accurate estimates of
the actual level of Plasmodium circulation within malaria vector populations.
PMID- 29344969
TI - Media experiences and associations with mental health among the bereaved of the
MH17-disaster: A latent profile analysis.
AB - Research has shown that the amount of media exposure is associated with post
event mental health problems. Whether bereaved individuals have negative
experiences with media reports and whether they are associated with post-event
mental health is unclear. This study evaluated these experiences and associations
following the MH17-disaster. How media reports were experienced (nine topics,
modified MAS), depression symptoms (QIDS-SR), functional problems (WSAS) and
event-related coping-self-efficacy (CSE) were assessed about one year post
disaster (May-August 2015) among Dutch bereaved (N = 152). A substantial minority
reported negative experiences such as reports made me angry (30%) and made me sad
(48%). Latent profile analysis with symptoms, problems and coping self-efficacy
as indicators, identified four classes of post-disaster mental health: a Well
functioning(class 1) , 35.1%; a Mild-problems(class 2) , 30.4%; a Sub
clinical(class 3) , 27.0%; and a Clinical(class 4) , 7.4%. Differences in
symptoms, problems and coping self-efficacy levels between classes were large
according to Cohen's ds. Multivariate logistic regression (MLR) showed that the
Clinical(class 4) compared to the Well-functioning(class 1) , more often that
felt that reports strongly "embarrassed me," "made me feel sad," "filled me with
fear" and "served as a magnifying glass." Future research should assess
opportunities and effects of limiting media consumption.
PMID- 29344970
TI - Carbon allocation to major metabolites in illuminated leaves is not just
proportional to photosynthesis when gaseous conditions (CO2 and O2 ) vary.
AB - In gas-exchange experiments, manipulating CO2 and O2 is commonly used to change
the balance between carboxylation and oxygenation. Downstream metabolism
(utilization of photosynthetic and photorespiratory products) may also be
affected by gaseous conditions but this is not well documented. Here, we took
advantage of sunflower as a model species, which accumulates chlorogenate in
addition to sugars and amino acids (glutamate, alanine, glycine and serine). We
performed isotopic labelling with 13 CO2 under different CO2 /O2 conditions, and
determined 13 C contents to compute 13 C-allocation patterns and build-up rates.
The 13 C content in major metabolites was not found to be a constant proportion
of net fixed carbon but, rather, changed dramatically with CO2 and O2 . Alanine
typically accumulated at low O2 (hypoxic response) while photorespiratory
intermediates accumulated under ambient conditions and at high photorespiration,
glycerate accumulation exceeding serine and glycine build-up. Chlorogenate
synthesis was relatively more important under normal conditions and at high CO2
and its synthesis was driven by phosphoenolpyruvate de novo synthesis. These
findings demonstrate that carbon allocation to metabolites other than
photosynthetic end products is affected by gaseous conditions and therefore the
photosynthetic yield of net nitrogen assimilation varies, being minimal at high
CO2 and maximal at high O2 .
PMID- 29344971
TI - Clear cell carcinomas of the ovary and kidney: clarity through genomics.
AB - Clear cell ovarian carcinoma (CCOC) and clear cell renal cell carcinoma (ccRCC)
both feature clear cytoplasm, owing to the accumulation of cytoplasmic glycogen.
Genomic studies have demonstrated several mutational similarities between these
two diseases, including frequent alterations in the chromatin remodelling SWI-SNF
and cellular proliferation phosphoinositide 3-kinase-mammalian target of
rapamycin pathways, as well as a shared hypoxia-like mRNA expression signature.
Although many targeted treatment options have been approved for advanced-stage
ccRCC, CCOC patients are still treated with conventional platinum and taxane
chemotherapy, to which they are resistant. To determine the extent of similarity
between these malignancies, we performed unsupervised clustering of mRNA
expression data from these cancers. This review highlights the similarities and
differences between these two clear cell carcinomas to facilitate knowledge
translation within future research efforts. Copyright (c) 2018 Pathological
Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
PMID- 29344972
TI - A patient with chronic labial oedema and nodular palatal lesions.
PMID- 29344973
TI - Use of Hysterosalpingo-Foam Sonography for Assessment of the Efficacy of Essure
Hysteroscopic Sterilization.
AB - OBJECTIVES: Hysterosalpingo-foam sonography (HyFoSy) has been suggested to be a
possible less invasive alternative to hysterosalpingography (HSG), which is the
reference standard for confirmation of tubal occlusion after Essure (Bayer AG,
Leverkusen, Germany) hysteroscopic sterilization. The purpose of our study was to
evaluate the accuracy of HyFoSy compared to HSG for confirmation of tubal
occlusion after Essure hysteroscopic sterilization. METHODS: A prospective study
included 90 patients who underwent Essure hysteroscopic sterilization. Twelve
weeks after the sterilization, 2-dimensional transvaginal ultrasonography was
performed to assess the microinsert position and was followed by HyFoSy and HSG
for evaluation of tubal occlusion. Patients with patent fallopian tubes on HSG
were scheduled for additional HSG procedures at 3-month intervals until tubal
occlusion was documented. RESULTS: Of 90 enrolled patients, 86 patients with 170
fallopian tubes underwent the complete imaging protocol. Tubal occlusion was
evaluated by HyFoSy as an index test and HSG as a reference standard. The
accuracy of HyFoSy was 97.1% (95% confidence interval [CI], 93%-99%). The
sensitivity and specificity were 100% (95% CI, 97%-100%) and 54.6% (95% CI, 23%
83%), whereas the positive and negative predictive values were 97.0% (95% CI, 93%
99%) and 100% (95% CI, 42%-100%), respectively. No long-term complications were
reported for HyFoSy or HSG. CONCLUSIONS: Given that the concordance rate for
tubal occlusion between HyFoSy and HSG was not 100%, an occluded fallopian tube
on HyFoSy should be confirmed by HSG, which remains the reference standard for
confirmation of tubal occlusion after Essure hysteroscopic sterilization.
PMID- 29344974
TI - Utilizing selected social determinants and behaviors to predict obesity in
military personnel.
AB - OBJECTIVE: Like the general population, the military is experiencing an increase
in the number of obese personnel. This study aimed to identify predictors of
obesity by assessing social determinants of health and behaviors in relation to
Body Mass Index (BMI), and to use these variables to build a model to predict
obesity in Active Duty Military Personnel (ADMP). Predicting obesity would allow
early intervention of at risk personnel, potentially reducing the number of ADMP
who are separated from the service for failing to meet weight standards. DESIGN:
A secondary data analysis of the 2011 Survey of Health-Related Behaviors of
Active Duty Military Personnel was performed. The survey included 39,197
responders. MEASURES: Descriptive statistics, bivariate analyses, and logistic
regression analysis were conducted to examine the relationship between social
determinants of health, behaviors in relation to Healthy People 2020
recommendations, and obesity. Moderator variables were used to determine what
affects the direction and/or strength of the relationship between the independent
variables (e.g., social determinants and behaviors) and the outcome variable of
obesity. RESULTS: At the bivariate level, these variables mirror existing
research. However, logistic regression identified few statistically significant
obesogenic lifestyle behaviors in relation to Healthy People 2020 recommendations
and a weak interactive effect between the variables. CONCLUSION: The low number
of significant variables identified to predict obesity highlights the
multifactorial nature of obesity making it difficult for weight-loss
interventions to be effective if limited to one group or one specific behavior.
PMID- 29344976
TI - Role of Elastography in Axillary Examination of Patients With Breast Cancer.
AB - OBJECTIVES: This study aimed at exploring the role of ultrasound (US)
elastography in the diagnosis of the axillary lymph node status in patients with
breast cancer. METHODS: We analyzed 140 visible axillary lymph nodes on
conventional US imaging. All of them underwent elastography. Five conventional US
features were adopted to assess axillary lymph nodes: longitudinal diameter,
longitudinal-to-transverse diameter ratio, cortical thickness, status of the
hilum, and vascular pattern. As for elastography, the proportion of the hard area
within each lymph node was estimated visually. The lymph node was defined as
positive on elastography when the proportion was 50% or greater. Meanwhile,
disjunctive and conjunctive combinations of US and elastography were adopted to
evaluate the lymph nodes. The histopathologic diagnosis was regarded as the
reference standard. RESULTS: The sensitivity, specificity, and accuracy were
76.92%, 87.10%, and 81.43%, respectively, for conventional US and 84.62%, 83.87%,
and 84.29% for the disjunctive combination. The conjunctive combination had
specificity of 100% and a positive predictive value of 100%, whereas the
sensitivity was low. CONCLUSIONS: Elastography can improve the sensitivity when
disjunctively combined with conventional US for diagnosis of the axillary lymph
node status. Despite the low sensitivity, the conjunctive combination of US and
elastography can improve the positive predictive value on a large scale.
Elastography is a useful adjuvant tool in addition to conventional US for the
preoperative assessment of axillary lymph nodes in patients with breast cancer.
PMID- 29344977
TI - There Is No Place Like Home: Imitation and the Politics of Recognition in
Bolivian Obstetric Care.
AB - This article examines how efforts to "culturally adapt" birthing spaces in a
rural Bolivian hospital are generating debates among doctors about what
constitutes proper obstetric care. Working at the intersection of national and
transnational projects, NGOs in Bolivia have remade the birthing rooms of some
public health institutions to look more like a home, with the goal of making
indigenous women feel more comfortable and encouraging them to come to the clinic
to give birth. Yet narratives of transformation also obscure ongoing conditions
of racial and gendered inequality in health services. I demonstrate how doctors'
use of culturally adapted technologies enacts shifting affective relations-warm,
cold, gentle, harsh-that draws on preoccupations with indigenous culture as a
threat to maternal and infant life. In tracing practices of care, I argue that
culturally adapted birthing in many ways extends historically rooted practices of
doing biomedical work on indigenous bodies.
PMID- 29344978
TI - Letter to the editor.
PMID- 29344979
TI - In vivo estimation of transverse relaxation time constant (T2 ) of 17 human brain
metabolites at 3T.
AB - PURPOSE: The transverse relaxation times T2 of 17 metabolites in vivo at 3T is
reported and region specific differences are addressed. METHODS: An echo-time
series protocol was applied to one, two, or three volumes of interest with
different fraction of white and gray matter including a total number of 106
healthy volunteers and acquiring a total number of 128 spectra. The data were
fitted with the 2D fitting tool ProFit2, which included individual line shape
modeling for all metabolites and allowed the T2 calculation of 28 moieties of 17
metabolites. RESULTS: The T2 of 10 metabolites and their moieties have been
reported for the first time. Region specific T2 differences in white and gray
matter enriched tissue occur in 16 of 17 metabolites examined including single
resonance lines and coupled spin systems. CONCLUSION: The relaxation time T2 is
regions specific and has to be considered when applying tissue composition
correction for internal water referencing. Magn Reson Med 80:452-461, 2018. (c)
2018 International Society for Magnetic Resonance in Medicine.
PMID- 29344975
TI - Extracellular matrix and traumatic brain injury.
AB - The brain extracellular matrix (ECM) plays a crucial role in both the developing
and adult brain by providing structural support and mediating cell-cell
interactions. In this review, we focus on the major constituents of the ECM and
how they function in both normal and injured brain, and summarize the changes in
the composition of the ECM as well as how these changes either promote or inhibit
recovery of function following traumatic brain injury (TBI). Modulation of ECM
composition to facilitates neuronal survival, regeneration and axonal outgrowth
is a potential therapeutic target for TBI treatment.
PMID- 29344980
TI - Analytical validation of a new point-of-care assay for serum amyloid A in horses.
AB - BACKGROUND: Serum amyloid A (SAA) is a major acute phase protein in horses. A new
point-of-care (POC) test for SAA (Stablelab) is available, but studies evaluating
its analytical accuracy are lacking. OBJECTIVES: To evaluate the analytical
performance of the SAA POC test by 1) determining linearity and precision, 2)
comparing results in whole blood with those in serum or plasma, and 3) comparing
POC results with those obtained using a previously validated turbidimetric
immunoassay (TIA). STUDY DESIGN: Assay validation. METHODS: Analytical validation
of the POC test was done in accordance with American Society of Veterinary
Clinical Pathology guidelines using residual equine serum/plasma and whole blood
samples from the Clinical Pathology Laboratory at the University of California
Davis. A TIA was used as the reference method. We also evaluated the effect of
haematocrit (HCT). RESULTS: The POC test was linear for SAA concentrations of up
to at least 1000 MUg/mL (r = 0.991). Intra-assay CVs were 13, 18 and 15% at high
(782 MUg/mL), intermediate (116 MUg/mL) and low (64 MUg/mL) concentrations. Inter
assay (inter-batch) CVs were 45, 14 and 15% at high (1372 MUg/mL), intermediate
(140 MUg/mL) and low (56 MUg/mL) concentrations. SAA results in whole blood were
significantly lower than those in serum/plasma (P = 0.0002), but were positively
correlated (r = 0.908) and not affected by HCT (P = 0.261); proportional negative
bias was observed in samples with SAA>500 MUg/mL. The difference between methods
exceeded the 95% confidence interval of the combined imprecision of both methods
(15%). MAIN LIMITATIONS: Analytical validation could not be performed in whole
blood, the sample most likely to be used stall side. CONCLUSION: The POC test has
acceptable accuracy and precision in equine serum/plasma with SAA concentrations
of up to at least 1000 MUg/mL. Low inter-batch precision at high concentrations
may affect serial measurements, and the use of the same test batch and sample
type (serum/plasma or whole blood) is recommended. Comparison of results between
the POC test and the TIA is not recommended.
PMID- 29344981
TI - Severe and recurrent levamisole-induced cutaneous vasculopathy.
PMID- 29344982
TI - Experience with pharmacologic leeching with bivalirudin for adjunct treatment of
venous congestion of head and neck reconstructive flaps.
AB - OBJECTIVES: The goal of this study was to review the feasibility of local
bivalirudin injection for adjunct treatment of venous congestion of head and neck
reconstructive flaps. METHODS: A retrospective chart review of patients who
underwent bivalirudin treatment for venous congestion of head and neck
reconstructive flaps in a single institution from September 1, 2012 to September
1, 2015 was undertaken. Individuals were treated with variable number of
intradermal injections directly into the flap followed by a small skin incision
to allow extended passive bleeding. The main outcome measure was improvement of
flap congestion. RESULTS: Ten patients with free flap reconstruction (4
anterolateral thigh flaps, 2 pectoralis major flaps, 2 fibula osseocutaneous
flaps, 1 supraclavicular flap, and 1 radial forearm free flap) of various head
and neck defects underwent treatment with bivalirudin. Bivalirudin injections
were utilized as adjunct therapy in 6 patients. Two individuals underwent
alternate therapy for venous congestion immediately following injection and
therefore the efficacy could not be assessed. Of the 8 remaining flaps, 4
developed partial necrosis, and 1 developed complete necrosis requiring
additional reconstruction. Two individuals required blood transfusions during
bivalirudin treatment. CONCLUSIONS: Bivalirudin is a safe and feasible adjunct
therapy for treatment of flap congestion. It may serve as a useful alternative to
traditional leech therapy, as bivalirudin negates the need for antibiotic
prophylaxis, eliminates the psychological aversion associated with leech therapy,
and avoids the potential for leech migration. Further work to determine the
efficacy of bivalirudin to standard leech therapy is warranted.
PMID- 29344984
TI - The editors respond to Drs Mowat and Sheehan.
PMID- 29344983
TI - Anti-inflammatory effect of 4-methylcyclopentadecanone in rats submitted to
ischemic stroke.
AB - This study aimed to investigate the anti-inflammatory effect of 4
methylcyclopentadecanone (4-MCPC) in rats suffering from a cerebral
ischemia/reperfusion (I/R) injury. In this study, the focal cerebral ischemia in
rats was induced by middle cerebral artery occlusion (MCAO) for 2 h, and the rats
were treated with 4-MCPC (8 mg/kg) just 0.5 h before reperfusion. The ischemic
infarct volume was recorded 24 h after the MCAO. In addition, myeloperoxidase
(MPO) activity and TNF-alpha and IL-1beta levels in the ischemic cerebral cortex
were determined by ELISA, while nuclear translocation of NF-kappaB p65 subunit
and expression of p-IkappaBalpha were investigated by Western blotting. Our
results showed that 4-MCPC treatment decreased infarct volume significantly,
compared with I/R group (16.8%+/-7.5% vs. 39.7%+/-10.9%); it reduced MPO activity
(0.43 +/- 0.10 vs. 1.00 +/- 0.51 U/g) and expression levels of TNF-alpha (18.90
+/- 3.65 vs. 35.87 +/- 4.87 ng/g) and IL-1beta (1.68 +/- 0.23 vs. 2.67 +/- 0.38
ng/g) in ischemic brain tissues of rats. Further study revealed that 4-MCPC
treatment markedly reduced nuclear translocation of NF-kappaB p65 subunit and
expression of p-IkappaBalpha in ischemic cerebral cortex. Taken together, our
results suggest that 4-MCPC protects against cerebral I/R injury and displays
anti-inflammatory actions through inhibition of the NF-kappaB signal pathway.
PMID- 29344985
TI - Probing the microscopic environment of 23 Na ions in brain tissue by MRI: On the
accuracy of different sampling schemes for the determination of rapid,
biexponential T2* decay at low signal-to-noise ratio.
AB - PURPOSE: To investigate and to reduce influences on the determination of the
short and long apparent transverse relaxation times ( T2,s*, T2,l*) of 23 Na in
vivo with respect to signal sampling. METHODS: The accuracy of T2* determination
was analyzed in simulations for five different sampling schemes. The influence of
noise in the parameter fit was investigated for three different models. A
dedicated sampling scheme was developed for brain parenchyma by numerically
optimizing the parameter estimation. This scheme was compared in vivo to linear
sampling at 7T. RESULTS: For the considered sampling schemes, T2,s* / T2,l*
exhibit an average bias of 3% / 4% with a variation of 25% / 15% based on
simulations with previously published T2* values. The accuracy could be improved
with the optimized sampling scheme by strongly averaging the earliest sample. A
fitting model with constant noise floor can increase accuracy while additional
fitting of a noise term is only beneficial in case of sampling until late echo
time > 80 ms. T2* values in white matter were determined to be T2,s* = 5.1 +/-
0.8 / 4.2 +/- 0.4 ms and T2,l* = 35.7 +/- 2.4 / 34.4 +/- 1.5 ms using
linear/optimized sampling. CONCLUSION: Voxel-wise T2* determination of 23 Na is
feasible in vivo. However, sampling and fitting methods have to be chosen
carefully to retrieve accurate results. Magn Reson Med 80:571-584, 2018. (c) 2018
International Society for Magnetic Resonance in Medicine.
PMID- 29344986
TI - Evaluation of bowel function in healthy children: untreated constipation is
common.
AB - AIM: We evaluated bowel function in healthy children with regard to gender and
age. METHODS: The study was carried out in 2016 at a tertiary children's
hospital. Healthy children aged 3.5 years to 15 years who were admitted to the
hospital, siblings to patients or offspring of staff members were included.
Validated self-report questionnaires and internally developed questions regarding
obstructive outlet- and gas-related symptoms were used. RESULTS: A total of 310
participants (50% girls) were included, which corresponded to a 94% answer
frequency. Respondents were divided into a younger age group (3.5 years to seven
years), consisting of 135 children, and an older age group (eight years to 15
years), consisting of 175 children. Younger children reported more foul odours
than older children (50% vs. 29%, p = 0.001) and more obstructive symptoms (21%
vs. 10%, p = 0.01). There was no difference between the age groups regarding
constipation (19% vs 16%, NS). Overall, 55% of those with constipation had no
treatment for the condition, although they reported abdominal pain (51%) and
problems with foul odours (57%). CONCLUSION: Healthy children frequently reported
constipation, abdominal pain and gas-related problems, but treatment was rare.
Overall, bowel function seemed to improve during childhood, although constipation
remained largely untreated.
PMID- 29344987
TI - Prior Uterine Evacuation and the Risk of Short Cervical Length: A Retrospective
Cohort Study.
AB - OBJECTIVES: To determine whether a prior uterine evacuation procedure is
associated with an increased risk of short cervical length (<=20 mm) in women
without prior spontaneous preterm birth. METHODS: This work was a retrospective
cohort study from January 2012 to December 2014 of singletons without prior
spontaneous preterm birth with cervical length screening between 18 weeks and 23
weeks 6 days. Women with a prior miscarriage/abortion were excluded if management
(medical, surgical, or expectant) was not specified. Prior uterine evacuation was
defined as dilation and curettage or dilation and evacuation of a spontaneous or
induced abortion. The primary outcome was the risk of short cervical length (<=20
mm) among women with and without 1 of more prior uterine evacuations at any
gestational age, assessed by the odds ratio and adjusted odds ratio for
confounders. RESULTS: Of 2672 women included, 714 (27%) had at least 1 prior
uterine evacuation. The overall incidence of short cervical length in the cohort
was 1% (n = 27). Women with at least 1 prior uterine evacuation were more likely
to be African American (64% versus 41%; P < .001), smoke (14% versus 8%; P <
.001), have a higher body mass index (mean +/- SD, 28.1 +/- 7.1 versus 26.8 +/-
7.1 kg/m2 ; P < .001), and have had prior full-term delivery (60% versus 41%; P <
.001). Women with at least 1 prior uterine evacuation had a significantly higher
incidence of short cervical length (2% versus 0.7%; P = .003; odds ratio, 2.99
[95% confidence interval, 1.40-6.40]). After adjustment for confounders, prior
uterine evacuation remained a source of increased risk of short cervical length
(adjusted odds ratio, 2.63 [95% confidence interval, 1.19-5.80]). CONCLUSIONS:
Although the overall incidence of short cervical length is low (1%-2%), women
with at least 1 prior uterine evacuation have at least a 2-fold increased risk of
a short second-trimester cervical length compared to women without a prior
uterine evacuation.
PMID- 29344988
TI - Recent advances in articular cartilage evaluation using computed tomography and
magnetic resonance imaging.
AB - Articular cartilage is a critical joint tissue and its evaluation remains a
diagnostic challenge in horses. Coupled with a poor capacity for healing, early
degenerative changes in articular cartilage are difficult to characterise using
routine diagnostic imaging evaluations. Both computed tomography (CT) and
magnetic resonance imaging (MRI) provide volumetric joint assessment and
highlight morphological and quantitative properties of articular cartilage,
improving assessment of this essential tissue. While the use of CT and MRI for
joint evaluation is not new, there still remains a shortage of literature and
scientific studies on the ability of these methods to evaluate articular
cartilage in the horse. This review article summarises current CT and MRI
techniques capable of characterising equine articular cartilage, highlights
recent advances in these techniques and discusses the numerous methods studied in
human subjects that have been minimally investigated in horses. Imaging
techniques are presented in terms of their capabilities of offering morphological
and quantitative evaluation along with a discussion of their benefits and
limitations. Finally, it summarises the current state-of-the-art approaches and
identifies unmet clinical imaging needs to propel the advancement of articular
cartilage and joint imaging in the horse.
PMID- 29344989
TI - Salmon calcitonin ameliorates migraine pain through modulation of CGRP release
and dural mast cell degranulation in rats.
AB - The exact mechanism of migraine pathophysiology still remains unclear due to the
complex nature of migraine pain. Salmon calcitonin (SC) exhibits antinociceptive
effects in the treatment of various pain conditions. In this study, we explored
the mechanisms underlying the analgesic effect of salmon calcitonin on migrane
pain using glyceryltrinitrate (GTN)-induced model of migraine and ex vivo
meningeal preparations in rats. Rats were intraperitoneally administered saline,
GTN (10 mg/kg), vehicle, saline + GTN, SC (50 MUg/kg) + GTN, and SC alone. Also,
ex vivo meningeal preparations were applied topically 100 MUmol/L GTN, 50 MUmol/L
SC, and SC + GTN. Calcitonin gene-related peptide (CGRP) contents of plasma,
trigeminal neurons and superfusates were measured using enzyme-immunoassays.
Dural mast cells were stained with toluidine blue. c-fos neuronal activity in
trigeminal nucleus caudalis (TNC) sections were determined by immunohistochemical
staining. The results showed that GTN triggered the increase in CGRP levels in
plasma, trigeminal ganglion neurons and ex vivo meningeal preparations. Likewise,
GTN-induced c-fos expression in TNC. In in vivo experiments, GTN caused dural
mast cell degranulation, but similar effects were not seen in ex vivo
experiments. Salmon calcitonin administration ameliorated GTN-induced migraine
pain by reversing the increases induced by GTN. Our findings suggested that
salmon calcitonin could alleviate the migraine-like pain by modulating CGRP
release at different levels including the generation and conduction sites of
migraine pain and mast cell behaviour in the dura mater. Therefore salmon
calcitonin may be a new therapeutic choice in migraine pain relief.
PMID- 29344990
TI - Self-gated golden-angle spiral 4D flow MRI.
AB - PURPOSE: The acquisition of 4D flow magnetic resonance imaging (MRI) in
cardiovascular applications has recently made large progress toward clinical
feasibility. The need for simultaneous compensation of cardiac and breathing
motion still poses a challenge for widespread clinical use. Especially, breathing
motion, addressed by gating approaches, can lead to unpredictable and long scan
times. The current work proposes a time-efficient self-gated 4D flow sequence
that exploits up to 100% of the acquired data and operates at a predictable scan
time. METHODS: A self-gated golden-angle spiral 4D flow sequence was implemented
and tested in 10 volunteers. Data were retrospectively binned into respiratory
and cardiac states and reconstructed using a conjugate-gradient sensitivity
encoding reconstruction. Net flow curves, stroke volumes, and peak flow in the
aorta were evaluated and compared to a conventional Cartesian 4D flow sequence.
Additionally, flow quantities reconstructed from 50% to 100% of the self-gated 4D
flow data were compared. RESULTS: Self-gating signals for respiratory and cardiac
motion were extracted for all volunteers. Flow quantities were in agreement with
the standard Cartesian scan. Mean differences in stroke volumes and peak flow of
7.6 +/- 11.5 and 4.0 +/- 79.9 mL/s were obtained, respectively. By
retrospectively increasing breathing navigator efficiency while decreasing
acquisition times (15:06-07:33 minutes), 50% of the acquired data were sufficient
to measure stroke volumes with errors under 9.6 mL. CONCLUSION: The feasibility
to acquire respiratory and cardiac self-gated 4D flow data at a predictable scan
time was demonstrated. Magn Reson Med 80:904-913, 2018. (c) 2018 International
Society for Magnetic Resonance in Medicine.
PMID- 29344991
TI - Relationship between enamel bond fatigue durability and surface free-energy
characteristics with universal adhesives.
AB - The relationship between enamel bond fatigue durability and surface free-energy
characteristics with universal adhesives was investigated. The initial shear bond
strengths and shear fatigue strengths of five universal adhesives to enamel were
determined with and without phosphoric acid pre-etching. The surface free-energy
characteristics of adhesive-treated enamel with and without pre-etching were also
determined. The initial shear bond strength and shear fatigue strength of
universal adhesive to pre-etched enamel were higher than those to ground enamel.
The initial shear bond strength and shear fatigue strength of universal adhesive
to pre-etched enamel were material dependent, unlike those to ground enamel. The
surface free-energy of the solid (gammaS ) and the hydrogen-bonding force
(gammaSh) of universal adhesive-treated enamel were different depending on the
adhesive, regardless of the presence or absence of pre-etching. The bond fatigue
durability of universal adhesives was higher to pre-etched enamel than to ground
enamel. In addition, the bond fatigue durability to pre-etched enamel was
material dependent, unlike that to ground enamel. The surface free-energy
characteristics of universal adhesive-treated enamel were influenced by the
adhesive type, regardless of the presence or absence of pre-etching. The surface
free-energy characteristics of universal adhesive-treated enamel were related to
the results of the bond fatigue durability.
PMID- 29344992
TI - An immunohistochemical score to predict the outcome for oral squamous cell
carcinoma.
AB - BACKGROUND: Oral cancer is a major public health problem worldwide, with a poor
survival. Our aim was to evaluate several protein markers in oral squamous cell
carcinomas (OSCC) and analyse their prognostic value on patient's survival.
METHODS: We analysed the expression of EGFR, p53, p27, p16, cyclin D1, cyclin A2,
COX-2, Ki-67, Bcl-2, VEGFR-1 and VEGFR-2, by immunohistochemistry on 67 primary
OSCC. Cancer-specific survival (CSS) analysis was evaluated by the Cox regression
model. RESULTS: Markers showed variable expression between 27.9% and 95.2%. In
univariate analysis for CSS, we found that four of the tested markers, namely
high expression of p53 (P = .001), EGFR (P = .003), cyclin A2 (P = .005) and low
expression of p16 (P = .019), along with clinical stage (P < .001), tumour size
(P < .001), presence of nodal metastasis (P < .001) and perineural permeation (P
= .039) were related to decreased survival. On the basis of these results, we
constructed an immunohistochemical score hinging on the possibility that any
tumour could express none of these four markers (score 0), one or two markers
(score 1) and three or more markers (score 2). In multivariable analysis, this
immunohistochemical score revealed an independent prognostic value on cancer
specific survival (P = .001; HR: 3.7: 95%CI 1.7-7.9). Moreover, we confirmed that
in early-stage tumours (stage I or II) this score maintained its independent
prognostic value (P = .025; HR: 7.9, 95%CI 1.3-49.1) on CSS. CONCLUSION: The
expression of the markers p53, p16, EGFR and cyclin A in OSCC, combined to give
an immunohistochemical score, may identify high-risk subgroups for decreased
survival and to further guide therapeutic decisions.
PMID- 29344993
TI - Editorial Comment to Cell death under epithelial-mesenchymal transition control
in prostate cancer therapeutic response.
PMID- 29344994
TI - Embryology of the craniocervical junction and posterior cranial fossa, part II:
Embryogenesis of the hindbrain.
AB - Although pathology of the hindbrain and its derivatives can have life altering
effects on a patient, a comprehensive review on its embryology is difficult to
find in the peer-reviewed medical literature. Therefore, this review article,
using standard search engines, seemed timely. The embryology of the hindbrain is
complex and relies on a unique timing of various neurovascular and bony elements.
Derailment of these developmental processes can lead to a wide range of
malformations such as the Chiari malformations. Therefore, a good working
knowledge of this embryology as outlined in this review of the hindbrain is
important for those treating patients with involvement of this region of the
central nervous system. Clin. Anat. 31:488-500, 2018. (c) 2018 Wiley Periodicals,
Inc.
PMID- 29344995
TI - Activation of human CD141+ and CD1c+ dendritic cells in vivo with combined TLR3
and TLR7/8 ligation.
AB - Mice reconstituted with human hematopoietic stem cells are valuable models to
study aspects of the human immune system in vivo. We describe a humanized mouse
model (hu mice) in which fully functional human CD141+ and CD1c+ myeloid and
CD123+ plasmacytoid dendritic cells (DC) develop from human cord blood CD34+
cells in immunodeficient mice. CD141+ DC are the human equivalents of murine CD8+
/CD103+ DC which are essential for the induction of tumor-inhibitory cytotoxic T
lymphocyte responses, making them attractive targets to exploit for the
development of new cancer immunotherapies. We used CD34+ -engrafted NSG-A2 mice
to investigate activation of DC subsets by synthetic dsRNA or ssRNA analogs
polyinosinic-polycytidylic acid/poly I:C and Resiquimod/R848, agonists for TLR3
and TLR8, respectively, both of which are expressed by CD141+ DC. Injection of hu
mice with these agonists resulted in upregulation of costimulatory molecules
CD80, CD83 and CD86 by CD141+ and CD1c+ DC alike, and their combination further
enhanced expression of these molecules by both subsets. When combined, poly I:C
and R848 enhanced serum levels of key cytokines associated with cross
presentation and the induction of cytotoxic T lymphocyte responses including IFN
alpha, IFN-beta, IL-12 and CXCL10. These data advocate a combination of poly I:C
and R848 TLR agonists as means of activating human DC for immunotherapy.
PMID- 29344996
TI - Bibliometric analysis of a century of research on oral erythroplakia and
leukoplakia.
AB - BACKGROUND: Oral squamous cell carcinoma is a major cause of cancer-associated
morbidity and mortality and may develop from oral erythroplakia and leukoplakia
(OEL), the most common oral potentially malignant lesions. Our objective was to
provide a descriptive overview of the global research activity on OEL over the
past decades. METHODS: We performed a systematic bibliometric analysis of
articles and reviews on OEL up to December 31st 2016 using the SCOPUS database.
Contribution of each country was analyzed by density-equalizing mapping (DEMP).
The overall scientific productivity was analyzed for each journal and country.
RESULTS: A total of 5098 published items (articles or reviews) were identified.
They are expected to double by 2040, with an expected number of 400 items per
year. Only 4% of all research on oral oncology is focused on OEL. Together with
the increasing number of publications since 1980s, an increasing number of
international collaborative studies were observed. Journal of Oral Pathology and
Medicine and Oral Oncology are the leading journals in terms of number of
published items. The US, India, and the UK were the most prolific countries in
terms of publications overtime. CONCLUSIONS: We identified the leading journals
as well as the leading authors and countries contributing to the research on OEL.
International collaborative studies in the field are to be encouraged to refine
strategies of oral cancer prevention.
PMID- 29344997
TI - Integration of Open Metal Sites and Lewis Basic Sites for Construction of a Cu
MOF with a Rare Chiral Oh -type cage for high performance in methane
purification.
AB - A Cu metal-organic framework (MOF), [Cu4 (PMTD)2 (H2 O)3 ]?20 H2 O, 1, (where
PMTD is 1,4-phenylenebis(5-methyl-4H-1,2,4-triazole-3,4-diyl)bis(5-carboxylato
3,1-phenylene)bis(hydroperoxymethanide)), with a rare chiral Oh -type cage, and
dual functionalities of open metal sites and Lewis basic sites, based on a
designed U-shaped ligand, was synthesized by hydrothermal methods. It exhibits
high CO2 , C2 , and C3 hydrocarbon storage capacity under atmospheric pressure,
as well as high H2 (1.96 wt.%) adsorption capacity at 77 K. Methane purification
capacity was tested and verified step by step. Isosteric heats (Qst ) studies
reveal that CH4 has the weakest van der Waals host-guest interactions among the
seven gases at 298 K. Ideal adsorbed solution theory (IAST) calculation reveals
that compound 1 is more selective toward CO2 , C2 H6 , and C3 H8 over CH4 in
further calculating its separation capacity, as exemplified for CO2 /CH4 (50:50,
5:95), C2 H6 /CH4 (50:50, 5:95), or C3 H8 /CH4 (50:50, 5:95) binary gas mixtures.
Breakthrough experiments show that 1 has a significantly higher adsorption
capacity for CO2 , C2 H6 , and C3 H8 than CH4 . The selective adsorption
properties of 1 make it a promising candidate for methane purification.
PMID- 29344998
TI - Role of AP-endonuclease (Ape1) active site residues in stabilization of the
reactant enzyme-DNA complex.
AB - Apurinic/apyrimidinic endonuclease 1 (Ape1) is an important metal-dependent
enzyme in the base excision repair mechanism, responsible for the backbone
cleavage of abasic DNA through a phosphate hydrolysis reaction. Molecular
dynamics simulations of Ape1 complexed to its substrate DNA performed for models
containing 1 or 2 Mg2+ -ions as cofactor located at different positions show a
complex with 1 metal ion bound on the leaving group site of the scissile
phosphate to be the most likely reaction-competent conformation. Active-site
residue His309 is found to be protonated based on pKa calculations and the higher
conformational stability of the Ape1-DNA substrate complex compared to scenarios
with neutral His309. Simulations of the D210N mutant further support the
prevalence of protonated His309 and strongly suggest Asp210 as the general base
for proton acceptance by a nucleophilic water molecule.
PMID- 29344999
TI - The newer classifications of the chiari malformations with clarifications: An
anatomical review.
AB - In 1891, Hans Chiari described a group of congenital hindbrain anomalies, which
were eventually named after him. He classified these malformations into three
types (Chiari malformations I, II, and III), and four years later added the
Chiari IV malformation. However, numerous reports across the literature do not
seem to fit Chiari's original descriptions of these malformations, so researchers
have been encouraged to propose new classifications to encompass these variants
(e.g., Chiari 0, Chiari1.5, and Chiari 3.5 malformations). Moreover, there is a
continued misunderstanding and misuse of the term "Chiari IV malformation."
Therefore, the current review intended to describe anatomical,
pathophysiological, and clinical aspects of the newer classifications with
clarifications of the Chiari malformations. We reviewed available literature
about Chiari malformations and their variants using "PubMed" and "Google
Scholar." We also looked into the term Chiari IV, clarifying its original
description and citing examples where the term has been used erroneously.
References in the reviewed articles were searched manually. Variants of the
originally described Chiari malformations are termed Chiari 0, Chiari 1.5, and
Chiari 3.5. Each has distinct anatomical characteristics and some of these are
extremely rare and incompatible with life (e.g. Chiari 3.5). Chiari IV
malformation has been further clarified. Some physicians might be unfamiliar with
the newer classifications of Chiari malformations because these conditions are
rare or even unique. Furthermore, care is needed in using the term "Chiari IV
malformation", which must be consistent with Chiari's original description, i.e.
an occipital encephalocele containing supratentorial contents. Clin. Anat. 31:314
322, 2018. (c) 2018 Wiley Periodicals, Inc.
PMID- 29345000
TI - Cell death under epithelial-mesenchymal transition control in prostate cancer
therapeutic response.
AB - Prostate cancer is a widespread problem among men, with >160 000 new cases in
2017 alone. Androgen deprivation therapy is commonly used in prostate cancer
treatment to block androgens required for cancer growth, but disease relapse
after androgen deprivation therapy is both common and severe. Changes in androgen
receptor signaling from androgen deprivation therapy have been linked to
therapeutic resistance and tumor progression. Resistant cells can become
reprogrammed to undergo epithelial-mesenchymal transition, a phenotypic switch
from benign, epithelial cells to a mobile cell with mesenchymal traits. In these
cells, attachment to their epithelial cell layer is no longer required for
survival. Anoikis is a form of cell death that occurs when detachment from other
cells and the basement membrane occurs. Epithelial cells have been shown to
undergo epithelial-mesenchymal transition, avoid anoikis induction and progress
to a metastatic phenotype. In prostate cancer progression to advanced disease,
epithelial-mesenchymal transition induction (characterized by loss of epithelial
cellular attachment protein E-cadherin) correlates with a higher Gleason score,
tumor progression, increased metastasis and higher biochemical recurrence. The
concept of interfacing epithelial-mesenchymal transition with anoikis in the
tumor microenvironment landscape will be discussed here, with focus on the
significance of the functional exchange between the two processes in therapeutic
targeting of advanced disease. The current evidence on the impact of loss of cell
cell contact, acquisition of chemoresistance, immune escape and metastatic spread
in advanced tumors in response to transforming growth factor-beta on prostate
cancer metastasis will be also discussed. The signaling cross-talk between
transforming growth factor-beta and androgen receptor signaling will be
interrogated as a new therapeutic platform for the development of combination
strategies to impair prostate cancer metastasis.
PMID- 29345001
TI - Wheat oral immunotherapy was moderately successful but was associated with very
frequent adverse events in children aged 6-18 years.
AB - AIM: This study investigated oral immunotherapy (OIT) for children aged 6-18
years with wheat allergies. METHODS: Well-cooked wheat spaghetti was given to 100
children with wheat allergies every day for 17 weeks, increasing from 0.3 to 2000
mg of wheat protein, followed by three- and nine-month maintenance phases. Blood
samples were taken before therapy and at follow-up visits. The study was carried
out in 2009-2015 in four Finnish paediatric allergology units. RESULTS: The
children (67% male) had a mean age of 11.6 years (range 6.1-18.6), and 57 were
using wheat daily 16 months after the initiation of therapy. Allergic symptoms
occurred in 94/100 children: mild in 34, moderate in 36 and severe in 24.
Specific immunoglobulin E (IgE) for omega-5-gliadin was significantly higher in
patients who did not reach the target dose and were related to the intensity of
reactions. CONCLUSION: The majority (57%) of children with wheat allergies could
use wheat in their daily diet 16 months after the initiation of OIT, but 94/100
had adverse reactions and 60 were moderate or severe. Specific IgE to omega-5
gliadin may provide a biomarker for how much wheat can be tolerated and the
intensity of the reactions to immunotherapy.
PMID- 29345002
TI - Remote C-H Activation of Various N-Heterocycles Using a Single Template.
AB - A single and simple ortho-sulfonyl benzonitrile template was developed to achieve
remote C-H olefination of six different classes of N-heterocycles. We demonstrate
that, by varying precatalysts and conditions, the same template can be applied to
the remote C-H activation of six structurally distinct heterocyclic scaffolds,
and the site-selectivity can be predicted based on distance and geometry.
Furthermore, this new development shows that template-directed remote C-H
activation is possible through macrocyclopalladation processes with smaller ring
sizes.
PMID- 29345003
TI - Investigation of attributes which guide choice in cataract surgery services in
urban Sydney, Australia.
AB - BACKGROUND: It is critical to consult patients to develop patient-centred
cataract surgery care. We aimed to identify attributes patients consider when
making decisions about cataract surgery in an Australian context, where both
publicly and privately funded surgery are available. This is the first step in
investigating how decisions are made about cataract surgery services. METHODS:
This observational qualitative study was undertaken in two public hospitals and
one private practice in Sydney, Australia. The study involved 19 women and men
with age-related cataracts and no previous cataract surgery, aged > 18 years,
able to speak conversational English or Mandarin. A multi-stage attribute
development process was followed, including: literature review, semi-structured
interviews with surgery candidates in three eye clinics, and review by an expert
panel. The main outcome measures were primary attributes for making choices about
cataract surgery. RESULTS: Wait time, cost, institutional reputation, surgeon
experience and travel time were identified as principal attributes; lower value
was placed on consultation length and accessibility. Non-English speaking
participants indicated greater interest in pre-operative information than English
speakers, but expressed trust in the Australian healthcare system. CONCLUSIONS:
Findings suggest individuals prioritise attributes which consume time or incur
costs when accessing care (wait time, cost and travel time). They also consider
factors associated with the outcome of their cataract surgery (surgeon experience
and institutional reputation). Similar to other decision-making processes,
patients are likely to trade between these different attributes depending on
their personal preferences and circumstances.
PMID- 29345004
TI - Epidermal permeability barrier function and sphingolipid content in the skin of
sphingomyelin synthase 2 deficient mice.
AB - Sphingomyelin synthase (SMS) is an enzyme that generates sphingomyelin (SM) from
ceramide (CER) and phosphatidylcholine. SM in the epidermis is a precursor of
CER, an important lipid for epidermal permeability barrier function. However, the
physiological role of SMS in skin is unclear. To uncover the function of SMS in
skin, we investigated sphingolipid metabolism enzyme activity in skin, SM content
in the epidermis, CER content in the stratum corneum (SC) and transepidermal
water loss (TEWL) as an indicator of barrier function in SMS2-knockout (KO) mice.
The activities of sphingolipid metabolism enzymes in skin homogenates were
measured using a fluorescently labelled substrate. Enzymatic reaction products
were detected by high-performance liquid chromatography (HPLC). Lipids in the
epidermis or SC were extracted and quantified by high-performance thin layer
chromatography (HPTLC). TEWL was measured using a Tewameter TM300. In SMS2-KO
mice, SMS activity in skin homogenates, epidermal SM content and SC CER content
were significantly decreased relative to wild-type (WT) mice. The TEWL of SMS2-KO
mice was significantly increased compared to WT mice. Our data indicate that SMS2
generates SM in the epidermis and contributes to epidermal permeability barrier
function and will support understanding of SM-related metabolic disorders.
PMID- 29345005
TI - "There's no acknowledgement of what this does to people": A qualitative
exploration of mental health among parents of children with critical congenital
heart defects.
AB - AIMS AND OBJECTIVES: The purpose of this study was to explore the psychological
impact of parenting a child with a critical congenital heart defect and the
feasibility and acceptability of integrating psychological services into
paediatric cardiology care. BACKGROUND: Children with critical congenital heart
defect are at an increased risk for long-term behavioural, social and emotional
difficulties. Data suggest that this risk is partially attributable to parental
mental health, which is a stronger predictor of long-term behavioural problems in
congenital heart defect children than disease-specific and surgical factors.
Parental stress and mental health are thus important intervention targets,
especially among high-risk families. DESIGN: This article presents data from a
qualitative study with 25 congenital heart defect parents (n = 15) and providers
(n = 10). METHODS: Using thematic analysis, semi-structured in-depth interviews
were transcribed and coded by the first and second author to identify major
themes and subthemes. RESULTS: Results of the interviews were organised into four
major themes: (i) the psychological impact of parenting a child with critical
congenital heart defect, (ii) factors that influence the psychological impact of
parenting a child with critical congenital heart defect, (iii) how and when to
psychologically support congenital heart defect parents and (iv) feasibility and
acceptability of integrating psychological support into congenital heart defect
care. Providers and parents endorsed the integration of mental health treatment
into routine congenital heart defect care and identified several practical issues
related to feasibility (e.g., funding and space) that should be considered prior
to implementation. CONCLUSIONS: Parents of children with critical congenital
heart defect need access to mental health services, and integrating these
services into routine paediatric cardiology care is a novel and practical way for
parents to receive the treatment they need. RELEVANCE TO CLINICAL PRACTICE:
Suggestions for how the field of paediatric cardiology could begin to integrate
mental health services into congenital heart defect treatment are provided.
PMID- 29345006
TI - Embryology of the craniocervical junction and posterior cranial fossa, part I:
Development of the upper vertebrae and skull.
AB - Although the embryology of the posterior cranial fossa can have life altering
effects on a patient, a comprehensive review on this topic is difficult to find
in the peer-reviewed medical literature. Therefore, this review article, using
standard search engines, seemed timely. The embryology of the posterior cranial
fossa is complex and relies on a unique timing of various neurovascular and bony
elements. Derailment of these developmental processes can lead to a wide range of
malformations such as the Chiari malformations. Therefore, a good working
knowledge of this embryology as outlined in this review of its bony architecture
is important for those treating patients with involvement of this region of the
cranium. Clin. Anat. 31:466-487, 2018. (c) 2018 Wiley Periodicals, Inc.
PMID- 29345007
TI - Aetiology of neonatal conjunctivitis evaluated in a population-based setting.
AB - AIM: Our aim was to study prospectively the aetiology of neonatal conjunctivitis
in a population-based setting. METHODS: Altogether 173 neonates with clinical
conjunctivitis aged on average 20 (SD 10) days were recruited from child welfare
clinics in Oulu, Finland, in 2010-2015. Conjunctival specimens were collected
from 167 neonates for multiplex polymerase chain reaction to detect 16
respiratory viruses, from 163 for polymerase chain reaction to detect Chlamydia
trachomatis and Neisseria gonorrhoeae and from 160 for bacterial culture studies.
The cases were followed up until the age of 18 months. RESULTS: Viral
conjunctivitis was diagnosed in 8/167 (4.8%; 95% CI 2.1-9.2%), chlamydial or
gonococcal conjunctivitis in 0/163 cases (0%; 95% CI 0-2.2%) and other bacterial
conjunctivitis in 58/160 (36%; 95% CI 29-44%). Rhinovirus was found at the ocular
site in 4/167 (2.4%) neonates, adenovirus in 3/167 (1.8%) and bocavirus in 1/167
(0.6%). The most commonly isolated bacteria included Staphylococcus aureus (16%),
Moraxella catarrhalis (9.4%) and Streptococcus pneumoniae (3.1%). None of these
pathogens was associated with the 4/173 (2.3%) cases later operated on for
persistent nasolacrimal duct obstruction. CONCLUSION: Chlamydia trachomatis was a
rare pathogen in neonatal conjunctivitis in a population-based setting, but
respiratory viruses were detected more frequently than indicated earlier.
PMID- 29345008
TI - Current knowledge of risk factors for testicular germ cell tumors.
AB - The development of the human gonads is tightly regulated by the correct
sequential expression of many genes and hormonal activity. Disturbance of this
regulation does not only prevent proper development of the gonads, but it also
contributes to the development of testicular germ cell tumors. Recent genetic
studies, especially genome-wide association studies, have made great progress in
understanding genetic susceptibility. Although there is strong evidence of
inherited risks, many environmental factors also contribute to the development of
testicular germ cell tumors. Histopathological studies have shown that most
testicular germ cell tumors arise from germ cell neoplasia in situ, which is
thought to be arrested and transformed primordial germ cells. Seminoma has
features identical to germ cell neoplasia in situ or primordial germ cells,
whereas non-seminoma shows varied differentiation. Seminomas and embryonic cell
carcinomas have the feature of pluripotency, which is thought to be the cause of
histological heterogeneity and mixed pathology in testicular germ cell tumors.
Testicular germ cell tumors show high sensitivity to chemotherapies, but 20-30%
of patients show resistance to standard chemotherapy. In the present review, the
current knowledge of the epidemiological and genomic factors for the development
of testicular germ cell tumors is reviewed, and the mechanisms of resistance to
chemotherapies are briefly mentioned.
PMID- 29345009
TI - Choosing non-redundant representative subsets of protein sequence data sets using
submodular optimization.
AB - Selecting a non-redundant representative subset of sequences is a common step in
many bioinformatics workflows, such as the creation of non-redundant training
sets for sequence and structural models or selection of "operational taxonomic
units" from metagenomics data. Previous methods for this task, such as CD-HIT,
PISCES, and UCLUST, apply a heuristic threshold-based algorithm that has no
theoretical guarantees. We propose a new approach based on submodular
optimization. Submodular optimization, a discrete analogue to continuous convex
optimization, has been used with great success for other representative set
selection problems. We demonstrate that the submodular optimization approach
results in representative protein sequence subsets with greater structural
diversity than sets chosen by existing methods, using as a gold standard the
SCOPe library of protein domain structures. In this setting, submodular
optimization consistently yields protein sequence subsets that include more SCOPe
domain families than sets of the same size selected by competing approaches. We
also show how the optimization framework allows us to design a mixture objective
function that performs well for both large and small representative sets. The
framework we describe is the best possible in polynomial time (under some
assumptions), and it is flexible and intuitive because it applies a suite of
generic methods to optimize one of a variety of objective functions.
PMID- 29345010
TI - Genetic variation in the shape of cold-survival curves in a single fly population
suggests potential for selection from climate variability.
AB - Temperature variation is one of the primary challenges facing ectotherms, and the
ability to tolerate a range of thermal environments is critical for setting
current and future species distributions. Low temperature is particularly
challenging for ectotherms because winter conditions have strong latitudinal and
temporal variation. Lower lethal temperature (LLT) is a common metric of cold
tolerance used in studies of local adaptation and plasticity. Comparisons of LLT
across groups typically assume parallel S-shaped survival curves, but genetic
variation in the shape of survival vs. temperature curves has not been assessed.
Here, we measured the ability of 36 lines of the Drosophila Genetic Reference
Panel (DGRP) to survive a 1-h cold shock at seven ecologically relevant low
temperatures (-1 to -7 degrees C) to create a high-resolution response curve for
each genotype. We observed surprising variation both in the magnitude of survival
and in the shapes of the response curves, with the curves clustering into four
distinct shapes. To encompass variation in the shapes of these survival curves,
we developed a new cold tolerance metric, cumulative cold tolerance (CCT). By
comparing our survival data with climatological data, we propose that variation
in the shapes of cold-survival curves arose from weak selection pressure to
survive intermediate subzero temperatures in this mid-latitude population of
flies. Using publicly available genome sequence and transcript expression data
for these lines, we identified several candidate genes associated with CCT, and
using transgenic RNAi, we confirmed a functional role for many of these genes.
PMID- 29345011
TI - Effectiveness of a patient education plan on knowledge of post-op venous
thromboembolism survival skills.
AB - AIMS AND OBJECTIVES: To investigate the effectiveness of a multimethod venous
thromboembolism prevention patient education plan on participants' knowledge
retention. BACKGROUND: A potential complication of surgery requiring general
anaesthesia, worldwide, is the development of life-threatening venous
thromboembolism. Patients need education on preventing, recognising and
immediately responding to a suspected thromboembolism. Written instructional
materials given to patients at discharge may be inadequate. DESIGN: A randomised
controlled trial. METHODS: Setting was multiple general surgery units at a large
Midwestern United States academic medical centre. Sample included patients
recovering from surgery with general anaesthesia: (N = 66), 68% female, 34 =
experimental, 32 = usual care. Prior to discharge, participants in the
experimental group were given a multimethod venous thromboembolism prevention
education plan including a video, pamphlet and verbal instruction; control group
received usual instructional pamphlet. Both groups received a knowledge test
immediately before instruction. Two weeks following discharge, a phone call was
made to participants to complete the postinstruction test. The relevant EQUATOR
guideline, CONSORT checklist, was used for reporting this study. CONCLUSIONS:
There were no statistically significant differences in age, gender, race, length
of stay, surgery and history of venous thromboembolism among participants and
group or test score results. No statistically significant difference in
postinstruction score was found between groups. However, there was a trend in
greater perception of importance in all groups and higher knowledge scores in the
experimental group, with the percentage of participants in the experimental group
answering all questions correctly rising from 38.2% correct to 73.5% correct.
RELEVANCE TO CLINICAL PRACTICE: Teaching patients the importance of knowing
venous thromboembolism signs and preventive/survival skills is potentially life
saving and nurses must know the importance of using the most effective methods
for the learning needs of their patients. Further research including different
education methods and testing is suggested.
PMID- 29345012
TI - In Reply to Letter to the Editor from Bhartiya: Transplantation of Whole Bone
Marrow Indicates That Bone Marrow Very Small Embryonic-Like Cells Do Not
Contribute to Endometrial Lineages.
PMID- 29345013
TI - Reliability and criterion-related validity testing (construct) of the
Endotracheal Suction Assessment Tool (ESAT(c)).
AB - AIMS AND OBJECTIVES: To establish criterion-related construct validity and test
retest reliability for the Endotracheal Suction Assessment Tool(c) (ESAT(c)).
BACKGROUND: Endotracheal tube suction performed in children can significantly
affect clinical stability. Previously identified clinical indicators for
endotracheal tube suction were used as criteria when designing the ESAT(c).
Content validity was reported previously. The final stages of psychometric
testing are presented. DESIGN: Observational testing was used to measure
construct validity and determine whether the ESAT(c) could guide "inexperienced"
paediatric intensive care nurses' decision-making regarding endotracheal tube
suction. Test-retest reliability of the ESAT(c) was performed at two time points.
METHODS: The researchers and paediatric intensive care nurse "experts" developed
10 hypothetical clinical scenarios with predetermined endotracheal tube suction
outcomes. "Experienced" (n = 12) and "inexperienced" (n = 14) paediatric
intensive care nurses were presented with the scenarios and the ESAT(c) guiding
decision-making about whether to perform endotracheal tube suction for each
scenario. Outcomes were compared with those predetermined by the "experts" (n =
9). Test-retest reliability of the ESAT(c) was measured at two consecutive time
points (4 weeks apart) with "experienced" and "inexperienced" paediatric
intensive care nurses using the same scenarios and tool to guide decision-making.
RESULTS: No differences were observed between endotracheal tube suction decisions
made by "experts" (n = 9), "inexperienced" (n = 14) and "experienced" (n = 12)
nurses confirming the tool's construct validity. No differences were observed
between groups for endotracheal tube suction decisions at T1 and T2. CONCLUSION:
Criterion-related construct validity and test-retest reliability of the ESAT(c)
were demonstrated. Further testing is recommended to confirm reliability in the
clinical setting with the "inexperienced" nurse to guide decision-making related
to endotracheal tube suction. RELEVANCE TO CLINICAL PRACTICE: The ESAT(c) is the
first validated tool to systematically guide endotracheal nursing practice for
the "inexperienced" nurse.
PMID- 29345014
TI - Concise Review: Human Induced Pluripotent Stem Cell Models of Retinitis
Pigmentosa.
AB - Hereditary retinal dystrophies, specifically retinitis pigmentosa (RP) are
clinically and genetically heterogeneous diseases affecting primarily retinal
cells and retinal pigment epithelial cells with blindness as a final outcome.
Understanding the pathogenicity behind these diseases has been largely precluded
by the unavailability of affected tissue from patients, large genetic
heterogeneity and animal models that do not faithfully represent some human
diseases. A landmark discovery of human induced pluripotent stem cells (hiPSCs)
permitted the derivation of patient-specific cells. These cells have unlimited
self-renewing capacity and the ability to differentiate into RP-affected cell
types, allowing the studies of disease mechanism, drug discovery, and cell
replacement therapies, both as individual cell types and organoid cultures.
Together with precise genome editing, the patient specific hiPSC technology
offers novel strategies for targeting the pathogenic mutations and design
therapies toward retinal dystrophies. This study summarizes current hiPSC-based
RP models and highlights key achievements and challenges of these cellular
models, as well as questions that still remain unanswered. Stem Cells 2018;36:474
481.
PMID- 29345015
TI - Dynamic sex chromosomes in Old World chameleons (Squamata: Chamaeleonidae).
AB - Much of our current state of knowledge concerning sex chromosome evolution is
based on a handful of 'exceptional' taxa with heteromorphic sex chromosomes.
However, classifying the sex chromosome systems of additional species lacking
easily identifiable, heteromorphic sex chromosomes is indispensable if we wish to
fully understand the genesis, degeneration and turnover of vertebrate sex
chromosomes. Squamate reptiles (lizards and snakes) are a potential model clade
for studying sex chromosome evolution as they exhibit a suite of sex-determining
modes yet most species lack heteromorphic sex chromosomes. Only three (of 203)
chameleon species have identified sex chromosome systems (all with female
heterogamety, ZZ/ZW). This study uses a recently developed method to identify sex
specific genetic markers from restriction site-associated DNA sequence (RADseq)
data, which enables the identification of sex chromosome systems in species
lacking heteromorphic sex chromosomes. We used RADseq and subsequent PCR
validation to identify an XX/XY sex chromosome system in the veiled chameleon
(Chamaeleo calyptratus), revealing a novel transition in sex chromosome systems
within the Chamaeleonidae. The sex-specific genetic markers identified here will
be essential in research focused on sex-specific, comparative, functional and
developmental evolutionary questions, further promoting C. calyptratus' utility
as an emerging model organism.
PMID- 29345016
TI - Evaluation of the implementation of a 24-hr stroke thrombolysis emergency
treatment for patients with acute ischaemic stroke.
AB - AIMS AND OBJECTIVES: To assess the trends of intravenous (IV) thrombolysis with
recombinant tissue plasminogen activator (rt-PA) among patients with acute
ischaemic stroke (AIS) admitted to our hospital between 2012-2014 and investigate
the effects of a 24-hr stroke thrombolysis emergency treatment on the
intrahospital clinical data and outcomes of these patients treated with IV rt-PA
thrombolysis. BACKGROUND: Although prenotification of stroke by emergency medical
services has been endorsed by the national recommendations and implemented in
some developed countries, the development in China is limited. DESIGN: A
retrospective, single-centre, observational study. METHODS: Patients with AIS
admitted to our hospital between January 2012-December 2014 were included; those
who received IV rt-PA thrombolysis within 4.5 hr of onset were investigated.
Demographic characteristics, including age and sex, and clinical data and
outcomes, including onset-to-treatment time (OTT), door-to-needle time (DNT),
premorbid modified Rankin Scale score and proportion of patients treated per
year, were all recorded. RESULTS: The proportion of patients with AIS who
received thrombolytic therapy within 4.5 hr increased from 2012-2014. The
baseline characteristics of all patients were similar. Since the implementation
of 24-hr stroke thrombolysis emergency treatment in 2013, the median DNT
significantly decreased in 2014 after implementation (42 min) compared with that
in 2012 before implementation (81 min) (p < .05). Moreover, the admission-to
imaging time (37 vs. 33 vs. 36 min) and OTT (176 vs. 147 vs. 124 min)
significantly decreased during the 3 years (p < .05). CONCLUSIONS: The 24-hr
stroke thrombolysis emergency treatment reduced in-hospital delay before
thrombolytic therapy but had no effect on the functional outcomes of the patients
with AIS. RELEVANCE TO CLINICAL PRACTICE: This study provides opportunities to
improve the experiences in using 24-h stroke thrombolysis emergency treatment in
patients with AIS in clinical practice.
PMID- 29345017
TI - Effects of nutritional support on short-term clinical outcomes and immune
response in unresectable locally advanced oesophageal squamous cell carcinoma.
AB - This retrospective study investigated the efficiency of nutritional support in
unresectable locally advanced oesophageal squamous cell carcinoma (LAOSCC)
patients who received concurrent chemoradiotherapy (CCRT) based on 5-fluorouracil
and cisplatin. In the routine care group, 63 patients served as historical
controls and received nutrition support in a reactive manner. In addition, 57
patients in the nutritional support group received timely diet counselling, oral
nutritional supplements, enteral nutrition and/or parenteral nutrition during
CCRT. This support was based on scores from nutritional risk screening 2002 (NRS
2002) after June 2014. The nutritional support group had significant advantages
over the routine care group with respect to the incidence of neutropenia, the
objective response rate, the change in serum albumin and the lengths of hospital
stay. In addition, the nutritional support group had significantly higher levels
of IgG and IL-2, higher proportions of NK, CD3+ and CD4+ cells as well as a
higher ratio of CD4+ /CD8+ cells than the routine care group (p < .05). In
contrast, the nutritional support group had a significantly lower level of IL-6.
In conclusion, the current nutritional care programme could bring benefits of
improving treatment compliance, reducing toxicity and lengths of hospital stay
and enhancing the immune response.
PMID- 29345018
TI - An Orphan Protist Quadricilia rotundata Finally Finds Its Phylogenetic Home in
Cercozoa.
AB - Quadricilia rotundata is a heterotrophic flagellate with four flagella. However,
because this species has no clear morphological characteristics or molecular data
affiliating it with any known group, Q. rotundata has been treated as a protist
incertae sedis, for a long time. Here, we established a clonal culture of Q.
rotundata and sequenced its 18S rDNA sequence. Molecular phylogenetic analysis
successfully placed Q. rotundata in an environmental clade within Cercozoa, which
contributes to expand the morphological and species diversity within Cercozoa. We
also discuss morphological evolution within Cercozoa based on this finding.
PMID- 29345019
TI - A vascular mechanism to explain thermally mediated variations in deep-body
cooling rates during the immersion of profoundly hyperthermic individuals.
AB - NEW FINDINGS: What is the central question of this study? Does the cold-water
immersion (14 degrees C) of profoundly hyperthermic individuals induce reductions
in cutaneous and limb blood flow of sufficient magnitude to impair heat loss
relative to the size of the thermal gradient? What is the main finding and its
importance? The temperate-water cooling (26 degrees C) of profoundly hyperthermic
individuals was found to be rapid and reproducible. A vascular mechanism
accounted for that outcome, with temperature-dependent differences in cutaneous
and limb blood flows observed during cooling. Decisions relating to cooling
strategies must be based upon deep-body temperature measurements that have
response dynamics consistent with the urgency for cooling. ABSTRACT:
Physiologically trivial time differences for cooling the intrathoracic viscera of
hyperthermic individuals have been reported between cold- and temperate-water
immersion treatments. One explanation for that observation is reduced convective
heat delivery to the skin during cold immersion, and this study was designed to
test both the validity of that observation, and its underlying hypothesis. Eight
healthy men participated in four head-out water immersions: two when
normothermic, and two after exercise-induced, moderate-to-profound hyperthermia.
Two water temperatures were used within each thermal state: temperate (26 degrees
C) and cold (14 degrees C). Tissue temperatures were measured at three deep-body
sites (oesophagus, auditory canal and rectum) and eight skin surfaces, with
cutaneous vascular responses simultaneously evaluated from both forearms (laser
Doppler flowmetry and venous-occlusion plethysmography). During the cold
immersion of normothermic individuals, oesophageal temperature decreased relative
to baseline (-0.31 degrees C over 20 min; P < 0.05), whilst rectal temperature
increased (0.20 degrees C; P < 0.05). When rendered hyperthermic, oesophageal (
0.75 degrees C) and rectal temperatures decreased (-0.05 degrees C) during the
transition period (<8.5 min, mostly in air at 22 degrees C), with the former
dropping to 37.5 degrees C only 54 s faster when immersed in cold rather than in
temperate water (P < 0.05). Minimal cutaneous vasoconstriction occurred during
either normothermic immersion, whereas pronounced constriction was evident during
both immersions when subjects were hyperthermic, with the colder water eliciting
a greater vascular response (P < 0.05). It was concluded that the rapid
intrathoracic cooling of asymptomatic, hyperthermic individuals in temperate
water was a reproducible phenomenon, with slower than expected cooling in cold
water brought about by stronger cutaneous vasoconstriction that reduced
convective heat delivery to the periphery.
PMID- 29345020
TI - A new approach in exploring satisfaction with nursing care by nurses themselves.
AB - AIMS AND OBJECTIVES: To examine the level of satisfaction with nursing care from
nurses' perspectives, as patients and/or as caregivers for hospitalised
relatives. BACKGROUND: Many studies that have examined patients' satisfaction
with nursing care in Jordan and worldwide found high ratings of satisfaction with
nursing care among patients. These ratings may be inflated because patients, as
the recipients of care, are often unequipped to judge specific aspects of care,
unless the patient is also a nurse. METHODS: A descriptive cross-sectional design
was used. Data were collected using the Patients Satisfaction with Nursing Care
Quality Questionnaire. The total sample size was 231 registered nurses from eight
hospitals in Jordan. All participating nurses had either experienced
hospitalisation for a minimum of 24 hr for themselves or as caregivers for one of
their close relatives, currently or within the last year. RESULTS: The average
age of participants was 31.7 (SD = 0.40) years. Most of the participants were
female with <10 years of work experience. The average score for the level of
satisfaction was 2.96 of 5, which reflects a moderate level of satisfaction with
nursing care. None of the 19 items of the satisfaction scale exceeded the
moderate level. The highest mean score of satisfaction level was 3.20 (SD = 1.17)
for the skills and competence of nurses, while the lowest mean score was 2.68
(1.22) for the coordination of care after discharge. CONCLUSION: Nurses as
patients and/or caregivers evaluated the nursing care during their
hospitalisation differently in comparison with public patients. The findings
indicated that nurses perceived only moderate levels of satisfaction when
undergoing experiences of hospitalisation. RELEVANCE TO CLINICAL PRACTICE: The
findings from this study may help nurses to become more alert for meeting the
patients' needs as desired under the best practice.
PMID- 29345021
TI - Effects of loneliness on illness perception in persons with a chronic disease.
AB - AIM AND OBJECTIVES: To determine the effects of loneliness on illness perception
in persons with a chronic disease. BACKGROUND: How an illness is perceived not
only affects all dimensions of a person's life but also plays an important role
in his/her coping with the complications and consequences of the disease. One of
the factors that influence the illness perception is loneliness. DESIGN: The
study is a descriptive study. METHODS: The study sample included 206 individuals
over the 18 years of age, conscious, having had a chronic illness at least 1
year, having no communication problems and agreeing to participate in the study
after being informed about the study. Data were collected with the Personal
Information Form, the Illness Perception Questionnaire and the University of
California Los Angeles Loneliness Scale. The forms were administered to the
participants in an unoccupied patient room, and the data were collected through
face-to-face interviews. RESULTS: The results of the study revealed that
individuals with a chronic disease perceived emotional symptoms accompanying the
disease more intensely that they accepted their disease was a chronic one and
that their personal control and treatment control of the disease were at a middle
level. The mean score the participants obtained from the University of California
Los Angeles Loneliness Scale was 38.49 +/- 11.15. There was a significant
negative correlation between this mean score and the mean scores obtained from
the following subscales consequences, treatment control, illness perception and
emotional representations. CONCLUSION: In this study, it was concluded that the
participants perceived their loneliness level as moderate and that their illness
perception was negatively affected as their loneliness levels increased.
RELEVANCE TO CLINICAL PRACTICE: The knowledge of clinical nurses about perception
of patients with chronic illnesses and conditions affecting that perception will
enhance compliance with the illness management or treatment strategies. Clinical
nurses should observe residents closely for signs of depression and loneliness
and support their sense of coherence to reduce emotional and social loneliness.
PMID- 29345023
TI - The narrow treatment road to survival: Everyday life perspectives of women with
breast cancer from Iraq and the former Yugoslavia undergoing radiation therapy in
Sweden.
AB - This study aimed at exploring how women from Iraq and the former Yugoslavia,
diagnosed with breast cancer and living in Sweden, experience their everyday life
during radiation therapy. A qualitative research design was used comprising
interviews with ten women, five originating from Iraq and five from the former
Yugoslavia. Striving to survive, the women experienced their everyday life during
radiation therapy as extremely challenging. This experience can be placed into
three categories: strategies for survival, keeping up appearances and staying in
control. Because of these specific challenges, immigrant women may need
additional information and guidance in conjunction with the diagnosis, which may
enable them to identify possible sources of support from those closest to them.
Also, greater attention should focus on acknowledging the woman behind the
diagnosis, regardless of her origin, to develop an individualised support
programme to help her cope with everyday life during radiation therapy.
PMID- 29345022
TI - Seroprevalence of Helicobacter pylori in Korea: A multicenter, nationwide study
conducted in 2015 and 2016.
AB - BACKGROUND: The Korean College of Helicobacter and Upper Gastrointestinal
Research has studied Helicobacter pylori (H. pylori) prevalence since 1998 and
found a dynamic change in its prevalence in Korea. The aim of this study was to
determine the recent H. pylori prevalence rate and compare it with that of
previous studies according to socioeconomic variables. METHODS: We planned to
enroll 4920 asymptomatic Korean adults from 21 centers according to the
population distribution of seven geographic areas (Seoul, Gyeonggi, Gangwon,
Chungcheong, Kyungsang, Cholla, and Jeju). We centrally collected serum and
tested H. pylori serum IgG using a chemiluminescent enzyme immunoassay. RESULTS:
We analyzed 4917 samples (4917/4920 = 99.9%) from January 2015 to December 2016.
After excluding equivocal serologic results, the H. pylori seropositivity rate
was 51.0% (2414/4734). We verified a decrease in H. pylori seroprevalence
compared with previous studies performed in 1998, 2005, and 2011 (P < .0001). The
H. pylori seroprevalence rate differed by area: Cholla (59.5%), Chungcheong
(59.2%), Kyungsang (55.1%), Jeju (54.4%), Gangwon (49.1%), Seoul (47.4%), and
Gyeonggi (44.6%). The rate was higher in those older than 40 years (38.1% in
those aged 30-39 years and 57.7% in those aged 40-49 years) and was lower in city
residents than in noncity residents at all ages. CONCLUSIONS: Helicobacter pylori
seroprevalence in Korea is decreasing and may vary according to population
characteristics. This trend should be considered to inform H. pylori-related
policies.
PMID- 29345024
TI - Being Pluripotent, Bone Marrow Very Small Embryonic-Like Stem Cells Rather Than
Hematopoietic Stem Cells Have the Potential to Regenerate Other Adult Organs.
PMID- 29345025
TI - The Royal Commission into child sexual abuse: A beginning, not an end.
PMID- 29345026
TI - Male-male aggression is unlikely to stabilize a poison frog polymorphism.
AB - Phenotypic polymorphism is common in animals, and the maintenance of multiple
phenotypes in a population requires forces that act against homogenizing drift
and selection. Male-male competition can contribute to the stability of a
polymorphism when males compete primarily with males of the same phenotype. In
and around a contact zone between red and blue lineages of the poison frog
Oophaga pumilio, we used simulated territorial intrusions to test the
nonexclusive predictions that males would direct more aggression towards males of
(i) their own phenotype and/or (ii) the phenotype that is most common in their
population. Males in the monomorphic red and blue populations that flank the
contact zone were more aggressive towards simulated intruders that matched the
local coloration. However, males in the two polymorphic populations biased
aggression towards neither their own colour nor the colour most common in their
population. In sympatry, the rarer colour morph gains no advantage via reduced
male-male aggression from territorial males in these O. pumilio populations, and
so male aggression seems unlikely to stabilize colour polymorphism on its own.
More broadly, these results suggest that the potential for divergent male
aggression biases to maintain phenotypic diversity depends on the mechanism(s)
that generate the biases and the degree to which these mechanisms persist in
sympatry.
PMID- 29345027
TI - Does flavoured dentifrice increase fluoride intake compared with regular
toothpaste in children? A systematic review and meta-analysis.
AB - BACKGROUND: Toothpaste manufacturers encourage through aggressive marketing
strategies the overconsumption of fluoridated dentifrices. There are conflicting
results regarding fluoride intake from toothpastes in children. AIM: The aim of
this systematic review and meta-analysis was to determine whether dentifrice
flavour increases fluoride ingestion by children. DESIGN: We included clinical
trials on children that evaluated the use of flavoured dentifrice - FD vs regular
dentifrice - RD to identify the fluoride intake. An electronic search was
performed in PubMed, Web of Science, Scopus, The Cochrane Library, LILACS/BBO,
and grey literature followed by manual search. The methodological quality of the
studies was assessed using the Cochrane Collaboration common scheme for bias and
ROBINS-I tool. Data were analysed in subgroups such as low (G1) and ordinary (G2)
fluoride concentrations of dentifrices. We carried out heterogeneity and
sensitive analyses. RESULTS: For G1, the fluoride intake from RD was
significantly higher than from FD [standardised mean difference = -2.57 (-3.26,
1.89), P < 0.00001]. For G2, the fluoride ingestion from RD was significantly
higher than from FD [mean difference = -0.00 (-0.00, -0.00), P = 0.02].
CONCLUSIONS: There is evidence to support the null hypothesis that flavouring
from dentifrice does not increase fluoride intake in young children.
PMID- 29345028
TI - Should we reserve big gun antimanic drugs for only big gun manias?
PMID- 29345029
TI - High prevalence and functional effects of serum antineuronal antibodies in
patients with gastrointestinal disorders.
AB - BACKGROUND: Antineuronal antibodies can be associated with both gastrointestinal
(GI) and brain disorders. For example, antibodies against the potassium channel
subunit dipeptidyl-peptidase-like protein-6 (DPPX) bind to neurons in the central
nervous system (CNS) and myenteric plexus and cause encephalitis, commonly
preceded by severe unspecific GI symptoms. We therefore investigated the
prevalence of antineuronal antibodies indicative of treatable autoimmune CNS
etiologies in GI patients. METHODS: Serum samples of 107 patients (Crohn's
disease n = 42, ulcerative colitis n = 16, irritable bowel syndrome n = 13,
others n = 36) and 44 healthy controls were screened for anti-DPPX and further
antineuronal antibodies using immunofluorescence on rat brain and intestine and
cell-based assays. Functional effects of high-titer reactive sera were assessed
in organ bath and Ussing chamber experiments and compared to non-reactive patient
sera. KEY RESULTS: Twenty-one of 107 patients (19.6%) had antibodies against the
enteric nervous system, and 22 (20.6%) had anti-CNS antibodies, thus
significantly exceeding frequencies in healthy controls (4.5% each). Screening on
cell-based assays excluded established antienteric antibodies. Antibody-positive
sera were not associated with motility effects in organ bath experiments.
However, they induced significant, tetrodotoxin (TTX)-insensitive secretion in
Ussing chambers compared to antibody-negative sera. CONCLUSIONS & INFERENCES:
Antineuronal antibodies were significantly more frequent in GI patients and
associated with functional effects on bowel secretion. Future studies will
determine whether such antibodies indicate patients who might benefit from
additional antibody-directed therapies. However, well-characterized encephalitis
related autoantibodies such as against DPPX were not detected, underlining their
rarity in routine cohorts.
PMID- 29345030
TI - Reproductive status-dependent kisspeptin and RFamide-related peptide (Rfrp) gene
expression in female Damaraland mole-rats.
AB - Damaraland mole rats (Fukomys damarensis) are cooperatively breeding,
subterranean mammals that exhibit a high reproductive skew. Reproduction is
monopolised by the dominant female of the group, whereas subordinates are
physiologically suppressed to the extent that they are anovulatory. In these
latter animals, it is assumed that normal gonadotropin-releasing hormone
secretion from the hypothalamus is disrupted. The RFamide peptides kisspeptin
(Kiss1) and RFamide-related peptide-3 (RFRP-3) are considered as potent
regulators of gonadotropin release. To assess whether these neuropeptides are
involved in the mechanism of reproductive suppression, we investigated the
distribution and gene expression of Kiss1 and Rfrp by means of in situ
hybridisation in wild-caught female Damaraland mole-rats with different
reproductive status. In both reproductive phenotypes, substantial Kiss1
expression was found in the arcuate nucleus and only few Kiss1-expressing cells
were detected in the anteroventral periventricular nucleus (AVPV), potentially as
a result of low circulating oestradiol concentrations in breeding and nonbreeding
females. Rfrp gene expression occurred in the dorsomedial nucleus, the
paraventricular nucleus and the periventricular nucleus. While in female breeders
and nonbreeders, plasma oestradiol levels were low and not significantly
different, quantification of the hybridisation signal for both genes revealed
significant differences in relation to reproductive status. Reproductively active
females had more Kiss1-expressing cells and a higher number of silver grains per
cell in the arcuate nucleus compared to nonreproductive females. This difference
was most pronounced in the caudal part of the nucleus. No such differences were
found in the AVPV. Furthermore, breeding status was associated with a reduced
number of Rfrp-expressing cells in the anterior hypothalamus. This reproductive
status-dependent expression pattern of Kiss1 and Rfrp suggests that both
neuropeptides play a role in the regulation of reproduction in Damaraland mole
rats. Enhanced long-term negative feedback effects of oestradiol could be
responsible for the lower Kiss1 expression in the arcuate nucleus of
reproductively suppressed females.
PMID- 29345031
TI - Amazon drought and forest response: Largely reduced forest photosynthesis but
slightly increased canopy greenness during the extreme drought of 2015/2016.
AB - Amazon droughts have impacted regional ecosystem functioning as well as global
carbon cycling. The severe dry-season droughts in 2005 and 2010, driven by
Atlantic sea surface temperature (SST) anomaly, have been widely investigated in
terms of drought severity and impacts on ecosystems. Although the influence of
Pacific SST anomaly on wet-season precipitation has been well recognized, it
remains uncertain to what extent the droughts driven by Pacific SST anomaly could
affect forest greenness and photosynthesis in the Amazon. Here, we examined the
monthly and annual dynamics of forest greenness and photosynthetic capacity when
Amazon ecosystems experienced an extreme drought in 2015/2016 driven by a strong
El Nino event. We found that the drought during August 2015-July 2016 was one of
the two most severe meteorological droughts since 1901. Due to the enhanced solar
radiation during this drought, overall forest greenness showed a small increase,
and 21.6% of forests even greened up (greenness index anomaly >=1 standard
deviation). In contrast, solar-induced chlorophyll fluorescence (SIF), an
indicator of vegetation photosynthetic capacity, showed a significant decrease.
Responses of forest greenness and photosynthesis decoupled during this drought,
indicating that forest photosynthesis could still be suppressed regardless of the
variation in canopy greenness. If future El Nino frequency increases as projected
by earth system models, droughts would result in persistent reduction in Amazon
forest productivity, substantial changes in tree composition, and considerable
carbon emissions from Amazon.
PMID- 29345032
TI - MiRNA-320a inhibits trophoblast cell invasion by targeting estrogen-related
receptor-gamma.
AB - AIM: MicroRNAs (miRs) play an essential role in the modulation of trophoblast
function. We explored miR-320a expression in the human placenta. In addition, we
report the promising effect and target functional loop of miR-320a in
trophoblasts. METHODS: MiR-320a expression was investigated in both pre-eclamptic
and healthy placenta tissues by quantitative real time-polymerase chain reaction
to determine how miR-320a affected invasion, proliferation and migration in
trophoblasts. A lipopolysaccharide (LPS) model was established in trophoblasts to
reveal how LPS supplementation stimulated miR-320a expression. Western blot was
applied to measure protein expression, which was involved in pathways modulated
by miR-320a in pre-eclamptic placentas. RESULTS: MiR-320a expression was enhanced
in the placental specimens of pre-eclamptic patients. Excessive miR-320a
expression remarkably suppressed trophoblast invasion but did not affect
migration or proliferation. However, transfection with miR-320a inhibitor
reinforced trophoblast invasion in vitro. Luciferase assays verified that
estrogen-related receptor-gamma (ERRgamma) served as a direct target of miR-320a.
Quantitative real-time polymerase chain reaction and Western blot demonstrated
that excessive miR-320a expression downregulated ERRgamma transcription and
translation. Additionally, LPS supplementation showed excessive miR-320a
expression and ERRgamma downregulation. Impaired ERRgamma and enhanced miR-320a
expression occurred in PE placentas compared to controls. Pearson correlation and
linear regression analysis revealed that miR-320a expression was negatively
related to ERRgamma expression in normal and pre-eclamptic placentas.
CONCLUSIONS: These findings indicate that miR-320a overexpression causes
anomalous placentation by targeting ERRgamma. Our research reveals the promising
effect of miR-320a and the ERRgamma functional loop on placentation.
PMID- 29345033
TI - Total Synthesis and Conformational Study of Callyaerin A: Anti-Tubercular Cyclic
Peptide Bearing a Rare Rigidifying (Z)-2,3- Diaminoacrylamide Moiety.
AB - The first synthesis of the anti-TB cyclic peptide callyaerin A (1), containing a
rare (Z)-2,3-diaminoacrylamide bridging motif, is reported. Fmoc-formylglycine
diethylacetal was used as a masked equivalent of formylglycine in the synthesis
of the linear precursor to 1. Intramolecular cyclization between the
formylglycine residue and the N-terminal amine in the linear peptide precursor
afforded the macrocyclic natural product 1. Synthetic 1 possessed potent anti-TB
activity (MIC100 =32 MUm) while its all-amide congener was inactive. Variable
temperature NMR studies of both the natural product and its all-amide analogue
revealed the extraordinary rigidity imposed by this diaminoacrylamide unit on
peptide conformation. The work reported herein pinpoints the intrinsic role that
the (Z)-2,3-diaminoacrylamide moiety confers on peptide bioactivity.
PMID- 29345034
TI - Precipitation frequency alters peatland ecosystem structure and CO2 exchange:
Contrasting effects on moss, sedge, and shrub communities.
AB - Climate projections forecast a redistribution of seasonal precipitation for much
of the globe into fewer, larger events spaced between longer dry periods, with
negligible changes in seasonal rainfall totals. This intensification of the
rainfall regime is expected to alter near-surface water availability, which will
affect plant performance and carbon uptake. This could be especially important in
peatland systems, where large stores of carbon are tightly coupled to water
surpluses limiting decomposition. Here, we examined the role of precipitation
frequency on vegetation growth and carbon dioxide (CO2 ) balances for communities
dominated by a Sphagnum moss, a sedge, and an ericaceous shrub in a cool
temperate poor fen. Field plots and laboratory monoliths received one of three
rainfall frequency treatments, ranging from one event every three days to one
event every 14 days, while total rain delivered in a two-week cycle and the
entire season to each treatment remained the same. Separating incident rain into
fewer but larger events increased vascular cover in all peatland communities:
vascular plant cover increased 6* in the moss-dominated plots, nearly doubled in
the sedge plots, and tripled in the shrub plots in Low-Frequency relative to High
Frequency treatments. Gross ecosystem productivity was lowest in moss communities
receiving low-frequency rain, but higher in sedge and shrub communities under the
same conditions. Net ecosystem exchange followed this pattern: fewer events with
longer dry periods increased CO2 flux to the atmosphere from the moss while
vascular plant-dominated communities became more of a sink for CO2 . Results of
this study suggest that changes to rainfall frequency already occurring and
predicted to continue will lead to increased vascular plant cover in peatlands
and will impact their carbon-sink function.
PMID- 29345035
TI - Pressure and pipes: from neuroimaging to virtual measurement.
PMID- 29345036
TI - Application of molecular tools to elucidate the microbiota of seafood.
AB - The aim of this review is to present the methodologies currently applied to
identify microbiota and pathogens transmitted to humans through seafood
consumption, focusing on molecular techniques and pointing out their importance,
advantages, disadvantages and applicability. Knowledge of available techniques
allows researchers to identify which technique best fits their expectations. With
such discernment, it will be possible to infer which disadvantages will be
present and, therefore, not interfering with the final result. Two methodologies
can be employed for this purpose, dependent and independent cultures. However,
the dependent culture has certain limitations that can be solved through the
independent cultivation techniques, such as PCR, PFGE and NGS, especially through
the sequencing of the 16S rRNA region, providing a complete view of microbial
diversity. These have revolutionized microbiological knowledge, mainly because
they allow for the identification of uncultivable micro-organisms, which
represent a substantial portion of total micro-organisms, making it possible to
elucidate not yet described taxa which may display pathogenic potential, besides
quantifying microbial communities, microbiota genetics, translated proteins and
produced metabolites. In addition, transcriptomic and metabolomic techniques also
allow for the evaluation of possible impacts that microbial communities may
create in their environment, as well as the determination of potential
pathogenicity to humans.
PMID- 29345037
TI - Prevalence of cognitive impairment in major depression and bipolar disorder.
AB - OBJECTIVES: The current study examines prevalence of cognitive impairment in four
mood disorder samples, using four definitions of impairment. The impact of
premorbid IQ on prevalence was examined, and the influence of treatment response.
METHODS: Samples were: (i) 58 inpatients in a current severe depressive episode
(unipolar or bipolar), (ii) 69 unmedicated outpatients in a mild to moderate
depressive episode (unipolar or bipolar), (iii) 56 outpatients with bipolar
disorder, in a depressive episode, and (iv) 63 outpatients with bipolar disorder,
currently euthymic. Cognitive assessment was conducted after treatment in Studies
1 (6 weeks of antidepressant treatment commenced on admission) and 2 (16-week
course of cognitive behaviour therapy or schema therapy), allowing the impact of
treatment response to be assessed. All mood disorder samples were compared with
healthy control groups. RESULTS: The prevalence of cognitive impairment was
highest for the inpatient depression sample (Study 1), and lowest for the
outpatient depression sample (Study 2). Substantial variability in rates was
observed depending on the definition of impairment used. Correcting cognitive
performance for premorbid IQ had a significant impact on the prevalence of
cognitive impairment in the inpatient depression sample. There was minimal
evidence that treatment response impacted on prevalence of cognitive impairment,
except in the domain of psychomotor speed in inpatients. CONCLUSIONS: As
interventions aiming to improve cognitive outcomes in mood disorders receive
increasing research focus, the issue of setting a cut-off level of cognitive
impairment for screening purposes becomes a priority. This analysis demonstrates
important differences in samples likely to be recruited depending on the
definition of cognitive impairment and begins to examine the importance of
premorbid IQ in determining who is impaired.
PMID- 29345038
TI - Electrocatalytic Activity of a 2D Phosphorene-Based Heteroelectrocatalyst for
Photoelectrochemical Cells.
AB - Research into efficient synthesis, fundamental properties, and potential
applications of phosphorene is currently the subject of intense investigation.
Herein, solution-processed phosphorene or few-layer black phosphorus (FL-BP)
sheets are prepared using a microwave exfoliation method and used in
photoelectrochemical cells. Based on experimental and theoretical (DFT) studies,
the FL-BP sheets are found to act as catalytically active sites and show
excellent electrocatalytic activity for triiodide reduction in dye-sensitized
solar cells. Importantly, the device fabricated based on the newly designed
cobalt sulfide (CoSx ) decorated nitrogen and sulfur co-doped carbon nanotube
heteroelectrocatalyst coated with FL-BP (FL-BP@N,S-doped CNTs-CoSx ) displayed an
impressive photovoltaic efficiency of 8.31 %, outperforming expensive platinum
based cells. This work paves the way for using phosphorene-based electrocatalysts
for next-generation energy-storage systems.
PMID- 29345039
TI - Successful treatment in a case of ultra-rapid cycling bipolar disorder is
reflected in brain arousal regulation.
PMID- 29345040
TI - Assessing and addressing cognitive impairment in bipolar disorder: the
International Society for Bipolar Disorders Targeting Cognition Task Force
recommendations for clinicians.
AB - OBJECTIVES: Cognition is a new treatment target to aid functional recovery and
enhance quality of life for patients with bipolar disorder. The International
Society for Bipolar Disorders (ISBD) Targeting Cognition Task Force aimed to
develop consensus-based clinical recommendations on whether, when and how to
assess and address cognitive impairment. METHODS: The task force, consisting of
19 international experts from nine countries, discussed the challenges and
recommendations in a face-to-face meeting, telephone conference call and email
exchanges. Consensus-based recommendations were achieved through these exchanges
with no need for formal consensus methods. RESULTS: The identified questions
were: (I) Should cognitive screening assessments be routinely conducted in
clinical settings? (II) What are the most feasible screening tools? (III) What
are the implications if cognitive impairment is detected? (IV) What are the
treatment perspectives? Key recommendations are that clinicians: (I) formally
screen cognition in partially or fully remitted patients whenever possible, (II)
use brief, easy-to-administer tools such as the Screen for Cognitive Impairment
in Psychiatry and Cognitive Complaints in Bipolar Disorder Rating Assessment, and
(III) evaluate the impact of medication and comorbidity, refer patients for
comprehensive neuropsychological evaluation when clinically indicated, and
encourage patients to build cognitive reserve. Regarding question (IV), there is
limited evidence for current evidence-based treatments but intense research
efforts are underway to identify new pharmacological and/or psychological
cognition treatments. CONCLUSIONS: This task force paper provides the first
consensus-based recommendations for clinicians on whether, when, and how to
assess and address cognition, which may aid patients' functional recovery and
improve their quality of life.
PMID- 29345041
TI - Serum amyloid A, procalcitonin, highly sensitive C reactive protein and tumor
necrosis factor alpha levels and acute inflammatory response in patients with
hemolysis, elevated liver enzymes, low platelet count (HELLP) and eclampsia.
AB - AIM: The aim of this study was to determine the relationship between serum
amyloid A (SAA), procalcitonin (ProC), highly sensitive C reactive protein
(hsCRP) and tumor necrosis factor (TNF) alpha activity in patients with pre
eclampsia, eclampsia and hemolysis, elevated liver enzymes, low platelet count
(HELLP), and the pathogenesis and severity of the disease. METHOD: Ninety
patients at >= 32 gestational weeks, according to the last date of menstruation
and ultra-sonographic measurements, diagnosed with pre-eclampsia (30 patients),
eclampsia (30 patients) or HELLP syndrome (30 patients) were included in the
study. Thirty healthy pregnant women from the outpatient clinic during the same
period were recruited as the control. The age, gravida, parity, gestational age,
systolic and diastolic blood pressures, proteinuria, hemoglobin, thrombocyte
count, liver function tests (aspartate aminotransferase, alanine
aminotransferase, lactate dehydrogenase, SAA, TNF alpha, ProC and hsCRP levels
during pregnancy) were determined and recorded. RESULTS: No statistically
significant differences were detected between the four groups in terms of age,
gravida, parity, gestational age and hemoglobin parameters (P > 0.05). When
compared to the control, systolic and diastolic blood pressures, spot and 24 h
urine protein levels, aspartate aminotransferase, alanine aminotransferase,
lactate dehydrogenase, SAA, ProC, hsCRP and TNF alpha levels were significantly
high and thrombocyte levels were low in the pre-eclamptic, eclamptic and HELLP
groups (P < 0.05). CONCLUSION: The investigated parameters were useful to gain an
understanding of the maternal inflammatory profile of pre-eclampsia and might be
beneficial as markers to predict complications such as HELLP and eclampsia and to
provide the necessary preventive approach in these patients.
PMID- 29345042
TI - A systematic review of community-based interventions for the treatment of
adolescents with overweight and obesity.
AB - Adolescent obesity is a risk factor for obesity and other chronic disease in
adulthood. Evidence for the effectiveness of community-based obesity treatment
programs for adolescents is required to inform policy and clinical decisions.
This systematic review aims to evaluate recent effective and scalable community
based weight management programs for adolescents (13-17 years) who are overweight
or obese. Eight databases (Medline, Embase, PsycINFO, CINAHL, Cochrane Central
Register of Controlled Trials, Cochrane Database of Systematic Reviews, Informit,
and Scopus) were searched for studies published between January 2011-2 March 2017
which are scalable in a community setting and reported primary outcome measures
relating to weight. Following deduplication, 10,074 records were screened by
title/abstract with 31 publications describing 21 programs included in this
review. Programs were heterogeneous in nature (including length, number and
frequency of sessions, parent-involvement and technology involvement). Reduction
in adolescent BMIz ranged from 2 to 9% post-program and from 2 to 11% after
varied lengths of follow-up. Study quality varied (n = 5 weak; n = 8 moderate; n
= 8 high), and findings are limited by the risk of selection and retention bias
in the included studies. Factors including the effectiveness and acceptability to
the target population must be considered when selecting such community programs.
PMID- 29345043
TI - Termiticidal activity of chitosan against the subterranean termites
Reticulitermes flavipes and Reticulitermes virginicus.
AB - BACKGROUND: Chitosan is a derivative form of chitin, which is the major component
of exoskeletons of arthropods and the cell walls of fungi. The antimicrobial
activity of chitosan against lepidopterans, aphids, fungi and bacteria has been
extensively investigated, but only one report on the termiticidal effect of
chitosan on termites has been published. In this study, we examined the
termiticidal activity of chitosan by exposing single colonies of Reticulitermes
flavipes (Kollar) and Reticulitermes virginicus Banks to wood treated with six
different concentrations of chitosan solutions. Termite mortality and percent
mass loss of wood samples after exposure to termites for 4 weeks were calculated.
RESULTS: High termite mortality (>= 94%) occurred during exposure of R. flavipes
termites to chitosan-treated wood with >=38 mg g-1 treatment concentrations (>=
2% chitosan), while <50% termite mortality was observed at lower treatment
concentrations (11-15 mg g-1 ; 0.5% and 1% chitosan). For R. virginicus, 100%
mortality was observed at all levels of treatment concentrations. A decrease in
the percent mass loss of the wood sample was apparent in samples treated with
solutions with an increasing chitosan concentration, with a significant
difference (P < 0.05) between lower and higher treatment concentrations.
Treatment retention in wood samples upon leaching was also determined and showed
retention levels of between 0 and 30 mg g-1 chitosan retention. CONCLUSION: This
study investigated the exposure of subterranean termites to chitosan as a wood
preservative. The results show that chitosan treatments at sufficiently high
loadings could protect wood against termites, preferably under non-leaching
conditions. (c) 2018 Society of Chemical Industry.
PMID- 29345044
TI - Pre-clinical Characterization of Absorption, Distribution, Metabolism and
Excretion Properties of TAK-063.
AB - TAK-063 is currently being developed to treat schizophrenia. In this study, we
investigated the absorption, distribution, metabolism and excretion (ADME)
properties of TAK-063 using several paradigms. Following oral administration of
TAK-063 at 0.3 mg/kg, bioavailability of TAK-063 was 27.4% in rats and 49.5% in
dogs with elimination half-lives of 3.1 hr in rats and 3.7 hr in dogs. TAK-063 is
a highly permeable compound without P-glycoprotein (P-gp) or breast cancer
resistance protein substrate liability and can be readily absorbed into systemic
circulation via the intestine. TAK-063 can also cross the blood-brain barrier.
TAK-063 was metabolized mainly by CYP2C8 and CYP3A4/5, while incubation with
human liver microsomes produced the major human metabolite, M-I as well as
several unknown minor metabolites. Metabolism of TAK-063 to M-I occurs through
hydroxylation of the mono-substituted pyrazole moiety. In vitro, TAK-063 was
observed to inhibit CYP2C8, CYP2C19 and P-gp with IC50 values of 8.4, 12 and 7.13
MUM, respectively. TAK-063 was primarily excreted in the faeces in rats and dogs
with M-I as a predominant component. The pre-clinical data from these ADME
studies demonstrate a favourable pharmacokinetic profile for TAK-063 with good
brain distribution supporting the feasibility of targeting central nervous system
regions involved in schizophrenia pathophysiology. TAK-063 has recently been
investigated in a phase 2 clinical trial (NCT02477020).
PMID- 29345045
TI - The in vitro release of cytokines and growth factors from fibrin membranes
produced through horizontal centrifugation.
AB - Platelet-rich fibrin membranes are biomaterials widely used for therapeutic
purposes, and canonically produced through the processing of peripheral blood
with fixed-angle rotor centrifuges. In this work, we evaluate the in vitro
stability and release of cytokines and growth factors when these biomaterials are
produced with a horizontal swing-out clinical centrifuge. Membranes produced from
the blood of 14 donors were morphologically evaluated by scanning electron
microscopy and fluorescence microscopy, and their stability was assessed by
photographic recording after incubation in culture medium for up to 28 days. The
release of 27 cytokines and growth factors was monitored for three weeks through
a multiparametric immunoassay. The fibrin membranes presented complex three
dimensional structure with a high density of nucleated cells. A large release of
growth factors [platelet derived growth factor, fibroblastic growth factor
(bFGF), and vascular endothelial growth factor] was detected in the first 24 h,
followed by time-dependent decay, maintaining significant concentrations after
three weeks. Both anti-inflammatory and pro-inflammatory cytokines presented
different release peaks, maintaining high rates of elution for up to 21 days.
Chemokines of relevance in tissue repair [RANTES, granulocyte colony-stimulating
factor (G-CSF)] were also produced in large quantities throughout the
experimental period. The present results demonstrate that blood-derived fibrin
membranes with high structural stability and cell content can be generated by
horizontal centrifugation, being able of a prolonged production/release of growth
factors and pro- and anti-inflammatory cytokines. (c) 2018 Wiley Periodicals,
Inc. J Biomed Mater Res Part A: 106A: 1373-1380, 2018.
PMID- 29345046
TI - Standardizing dose in dosimetric bronchial challenge tests.
AB - Recent technical recommendations on bronchial challenge testing aim at
standardized assessment of provocative dose of causing 20% decrease in FEV1
(PD20). The aim of this study was to investigate the effect of mode of
nebulization on the output of a computerized dosimeter (APS) and to compare PD20
obtained by two different dosimetric systems in vivo. The output of the APS
system was tested during continuous nebulization, and using simulated breaths,
for intermittent actuations with four different durations. Using output data, a
modified methacholine challenge protocol was applied for APS and compared with a
standard set-up using Spira dosimeter in 14 asthmatic patients attending
duplicate methacholine challenges using both systems, within median (range) 3 (1
6) days apart. The calculated output (mg min-1 ) with all the intermittent mode
settings was significantly higher (P<0.001) than in the continuous mode, and in
the intermittent mode, the output was dependent of the pulse duration. The PD20
values assessed with the APS and Spira systems were significantly correlated (r =
0.69; P<0.007), without systematic difference in the geometric means (P = 0.10).
A moderate to good agreement was found for assessment of significant
hyperresponsiveness. The results suggest that in dosimetric systems for bronchial
challenge tests, the output of the nebulizer is dependent on the mode of
nebulization, and this should be considered when standardizing the dose between
devices and protocols. As long as the delivered dose is determined for the
specified nebulization mode of the protocol, it may be possible to obtain
comparable results between different devices.
PMID- 29345047
TI - Effects of maternal heart sounds on pain and comfort during aspiration in preterm
infants.
AB - AIM: This study aimed to evaluate the effects of providing prerecorded maternal
heart sounds on the level of pain and comfort that are experienced by preterm
infants during aspiration. METHODS: This was a randomized controlled trial.
Preterm infants (N = 62) who were receiving care or treatment at a neonatal
intensive care unit were eligible for participation in this study. Infants in the
intervention group (n = 32) were provided with prerecorded maternal heart sounds
before, during, and after aspiration, whereas the infants in the control group (n
= 30) received routine care. For the collection of the data, the "Preterm Infant
Information Form" was used to record natal and postnatal information of the
preterm infant, the "Premature Infant Pain Profile," assessed the level of pain,
and the "Premature Infant Comfort Scale," assessed the level of comfort. RESULTS:
There was a significant difference observed between the groups' pain levels
during aspiration; however, the difference was not significant before and after
aspiration. Furthermore, there was a significant difference observed between the
groups' comfort levels prior to aspiration before and during aspiration; however,
the difference was not significant after aspiration. CONCLUSION: Intervention
with maternal heart sounds during aspiration effectively reduced pain and
provided comfort to the premature infants.
PMID- 29345048
TI - Urinary incontinence type, symptoms, and quality of life: A comparison between
grand multipara and non-grand multipara women aged >=50 years.
AB - AIM: Parity and age are risk factors for urinary incontinence (UI). The aim of
this study was to compare grand multipara women (GMP) to non-grand multipara
(NGMP) women concerning UI types (stress urinary incontinence [SUI], urge urinary
incontinence [UUI]), symptoms, and quality of life. METHODS: This correlation
comparative study used three tools: a demographic/health questionnaire,
Questionnaire for Urinary Incontinence Diagnosis (QUID), and Incontinence Quality
of Life (I-QOL). RESULTS: The sample included 132 women, from 50-88 years of age:
65 NGMP women (mean age: 67.23 years) and 67 GMP women (mean age: 65.04 years).
The GMP group had a higher score, compared to the NGMP group, for UI type (by
QUID) and a lower QOL (by I-QOL) , with none of the scores found to be
statistically significant. By dividing the sample into age groups, 50-59 and >=60
years, the interaction between the parity and the age groups was found to be
significant for both the SUI and UUI. CONCLUSION: The innovation of this study is
the in-depth insight into the association between parity and age regarding UI
type.
PMID- 29345049
TI - Cryolipolysis for the treatment of submental fat: Review of the literature.
AB - BACKGROUND: Submental fat accumulation is a common cosmetic concern.
Cryolipolysis utilizes noninvasive cooling to lyse adipocytes. A cryolipolysis
device was recently approved for treatment of submental fat. OBJECTIVE: This
manuscript provides a review of the preclinical work and clinical trials related
to cryolipolysis for the treatment of submental fat. Settings, efficacy, and side
effects are also discussed. MATERIALS AND METHODS: A literature search was
performed through Pubmed, EMBASE, Web of Science, and CINAHL, using the search
terms "cryolipolysis," "submental," and "paradoxical adipose hyperplasia".
Additional sources from the original source bibliographies were used to further
supplement this review. RESULTS: There are 4 clinical trials and one case series
(total 101 patients) that evaluated the use of cryolipolysis for treatment of
submental fat. In these studies, there was a statistically significant reduction
in submental fat and patients expressed high satisfaction with the treatment.
Adverse effects were mild and transient. CONCLUSIONS: Cryolipolysis is a
noninvasive cooling technique that is safe and effective for treatment of
submental fat. To date, there are no reports of marginal mandibular nerve injury
or paradoxical adipose hyperplasia following treatment with this device.
PMID- 29345050
TI - Metabolic alterations in a rat model of hepatic ischaemia reperfusion injury: In
vivo hyperpolarized 13 C MRS and metabolic imaging.
AB - BACKGROUND & AIMS: Despite a number of studies addressing the pathophysiology of
hepatic IRI, a gold standard test for early diagnosis and evaluation of IRI
remains elusive. This study investigated the metabolic alterations in a rat model
of hepatic IRI using the in vivo hyperpolarized 13C MRS and metabolic imaging.
METHODS: Hyperpolarized 13 C MRS with IVIM-DWI was performed on the liver of 7
sham-operated control rats and 7 rats before and after hepatic IRI. RESULTS: The
hepatic IRI-induced rats showed significantly higher ratios of [1-13 C]
alanine/pyruvate, [1-13 C] alanine/tC, [1-13 C] lactate/pyruvate and [1-13 C]
lactate/tC compared with both sham-operated controls and rats before IRI, whereas
[1-13 C] pyruvate/tC ratio was decreased in IRI-induced rats. In IVIM-DWI study,
apparent diffusion coefficient (ADC), f and D values in rats after hepatic IRI
were significantly lower than those of rats before IRI and sham-operated
controls. The levels of [1-13 C] alanine and [1-13 C] lactate were negatively
correlated with ADC, f and D values, whereas the level of [1-13 C] pyruvate was
positively correlated with these values. CONCLUSIONS: The levels of [1-13 C]
alanine, [1-13 C] lactate and [1-13 C] pyruvate in conjunction with IVIM-DWI will
be helpful to evaluate the hepatic IRI as well as these findings can be useful in
understanding the biochemical mechanism associated with hepatic damage.
PMID- 29345051
TI - MiR-595 Suppresses the Cellular Uptake and Cytotoxic Effects of Methotrexate by
Targeting SLC19A1 in CEM/C1 Cells.
AB - The human solute carrier family 19 member 1 (SLC19A1) is the gene coding for
reduced folate carrier 1 (RFC1). In our previous work, we showed that the miR-595
related polymorphism, rs1051296 G>T, which was located in the 3'-untranslated
region (3'-UTR) of SLC19A1, was associated with high methotrexate (MTX) plasma
concentrations in patients with paediatric acute lymphoblastic leukaemia (ALL).
This study aimed to investigate the role of miR-595 in the regulation of SLC19A1
expression and its effects on the cellular uptake and cytotoxicity of MTX in ALL
CEM/C1 cells. Luciferase reporter assay was performed to validate SLC19A1 as a
miR-595 target. RFC1 protein expression was determined via Western blotting.
Intracellular MTX concentrations were measured by enzyme-linked immunosorbent
assay (ELISA). Cell viability and apoptosis were assessed using Cell Counting Kit
8 (CCK-8) assay and flow cytometer, respectively. Compared to the negative
control, miR-595 mimics induced a significant decrease in the relative luciferase
activity by binding to the 3'-UTR of SLC19A1 harbouring the rs1051296 T allele (p
< 0.01). Treatment of CEM/C1 cells with miR-595 mimics substantially reduced RFC1
protein expression, intracellular MTX levels, MTX-induced cytotoxicity and
apoptosis rates compared to those of negative control. However, opposite results
were observed in cells transfected with a miR-595 inhibitor. These findings
suggested that miR-595 acts as a phenotypic regulator of MTX sensitivity in
CEM/C1 cells by targeting SLC19A1. This study helped us to understand the
mechanisms underlying the variable MTX responses observed in patients with ALL.
PMID- 29345052
TI - HpaP, a novel regulatory protein with ATPase and phosphatase activity,
contributes to full virulence in Xanthomonas campestris pv. campestris.
AB - The ability of the bacterial phytopathogen Xanthomonas campestris pv. campestris
(Xcc) to cause disease is dependent on the type III secretion system (T3SS).
Proteins of the Xcc T3SS are encoded by hrp (hypersensitive response and
pathogenicity) genes and whose expression is mainly controlled by the regulators
HrpG and HrpX. Here, we describe the identification and characterization of a
previously unknown regulatory protein (named HpaP), which plays important role in
hrp gene expression and virulence in Xcc. Clean deletion of hpaP demonstrated
reduced virulence and HR (hypersensitive response) induction of Xcc and
alterations in cell motility and stress tolerance. Global transcriptome analyses
revealed that most hrp genes were down regulated in the hpaP mutant, suggesting
HpaP positively regulates hrp genes. GUS activity assays implied that HpaP
regulates the expression of hrp genes via controlling the expression of hrpX.
Biochemical analyses revealed that HpaP protein had both ATPase and phosphatase
activity. While further site-directed mutagenesis of conserved residues in the
PTP loop (a protein tyrosine phosphatase signature) of HpaP resulted in the loss
of both phosphatase activity and regulatory activity in virulence and HR. Taken
together, the findings identify a new regulatory protein that controls hrp gene
expression and virulence in Xcc.
PMID- 29345053
TI - Naringenin (4,5,7-trihydroxyflavanone) suppresses the development of precancerous
lesions via controlling hyperproliferation and inflammation in the colon of
Wistar rats.
AB - Colon cancer is a world-wide health problem and one of the most dangerous type of
cancer, affecting both men and women. Naringenin (4, 5, 7-trihydroxyflavanone) is
one of the major flavone glycoside present in citrus fruits. Naringenin has long
been used in Chinese's traditional medicine because of its exceptional
pharmacological properties and non-toxic nature. In the present study, we
investigated the chemopreventive potential of Naringenin against 1,2
dimethyhydrazine (DMH)-induced precancerous lesions, that is, aberrant crypt foci
(ACF) and mucin depleted foci (MDF), and its role in regulating the oxidative
stress, inflammation and hyperproliferation, in the colon of Wistar rats. Animals
were divided into five groups. In groups 3-5, Naringenin was administered at the
dose of 50 mg/kg b. wt. orally while in groups 2-4, DMH was administered
subcutaneously in the groin at the dose of 20 mg/kg b. wt. once a week for first
5 weeks and animals were euthanized after 10 weeks. Administration of Naringenin
ameliorated the development of DMH-induced lipid peroxidation, ROS formation,
precancerous lesions (ACF and MDF) and it also reduced the infiltration of mast
cells, suppressed the immunostaining of NF-kappaB-p65, COX-2, i-NOS PCNA and Ki
67 Naringenin treatment significantly attenuated the level of TNF-alpha and it
also prevented the depletion of the mucous layer. Our findings suggest that
Naringenin has strong chemopreventive potential against DMH-induced colon
carcinogenesis but further studies are warranted to elucidate the precise
mechanism of action of Naringenin.
PMID- 29345054
TI - Isoflurane anesthesia in aged mice and effects of A1 adenosine receptors on
cognitive impairment.
AB - AIMS: Isoflurane may not only accelerate the process of Alzheimer's disease (AD),
but increase the risk of incidence of postoperative cognitive dysfunction (POCD).
However, the underlying mechanisms remain unknown. This study was designed to
investigate whether isoflurane contributed to the POCD occurrence through A1
adenosine receptor (A1AR) in aged mice. METHODS: We assessed cognitive function
of mice with Morris water maze (MWM) and then measured expression level of two AD
biomarkers (P-tau and Abeta) and a subtype of the NMDA receptor (NR2B) in aged
wild-type (WT) and homozygous A1 adenosine receptor (A1AR) knockout (KO) mice at
baseline and after they were exposed to isoflurane (1.4% for 2 hours). RESULTS:
For cognitive test, WT mice with isoflurane exposure performed worse than the WT
mice without isoflurane exposure. However, A1AR KO mice with isoflurane exposure
performed better than WT mice with isoflurane exposure. WT mice exposed to
isoflurane had increased levels of Abeta and phosphorylated tau (P-tau). Levels
of Abeta and P-tau were decreased in A1AR KO mice, whereas no differences were
noted between KO mice with and without isoflurane exposure. NR2B expression was
inversely related to that of P-tau, with no differences found between KO mice
with and without isoflurane exposure. CONCLUSIONS: We found an association
between isoflurane exposure, impairment of spatial memory, decreasing level of
NR2B, and increasing levels of A-beta and P-tau, presumably via the activation of
the A1A receptor.
PMID- 29345055
TI - Npas4 deficiency interacts with adolescent stress to disrupt prefrontal GABAergic
maturation and adult cognitive flexibility.
AB - Healthy cognitive and emotional functioning relies on a balance between
excitatory and inhibitory neurotransmission in the prefrontal cortex (PFC). This
balance is largely established during early postnatal and adolescent
developmental periods by maturation of the gamma-aminobutyric acid (GABA) system,
including increased density of parvalbumin (PV) cells and perineuronal nets
(PNNs). Genetic and/or environmental factors during adolescence can disrupt
GABAergic maturation and lead to behavioral dysfunction in adulthood. The present
study examined the interaction between chronic mild stress during adolescence and
genetic deficiency of neuronal Per-Arnt-Sim domain 4 (Npas4), a brain-specific
transcription factor that regulates inhibitory neurotransmission and that
contributes to adolescent prefrontal GABAergic maturation. Male Npas4 wild-type
(WT) and heterozygous (HET) mice were exposed to adolescent chronic stress and
tested in adulthood for cognitive function using the attention set shifting task.
When Npas4 deficiency was combined with adolescent stress, mice displayed
impaired cognitive flexibility as observed by poor performance on the extra
dimensional set shift task. At the cellular level, adolescent stress increased
the percentage of PV cells surrounded by PNNs in the PFC of adult WT animals, an
effect that was not observed in HET mice. Additionally, Npas4 deficiency and/or
adolescent stress dysregulated expression of certain GABAergic system markers.
These results suggest that Npas4 mediates susceptibility to adolescent stress and
subsequent cognitive functioning and inhibitory tone in adulthood. This shows a
novel gene by environment interaction related to resilience vs vulnerability to
stress, with implications for adolescent onset disorders like schizophrenia.
PMID- 29345056
TI - For when bacterial infections persist: Toll-like receptor-inducible direct
antimicrobial pathways in macrophages.
AB - Macrophages are linchpins of innate immunity, responding to invading
microorganisms by initiating coordinated inflammatory and antimicrobial programs.
Immediate antimicrobial responses, such as NADPH-dependent reactive oxygen
species (ROS), are triggered upon phagocytic receptor engagement. Macrophages
also detect and respond to microbial products through pattern recognition
receptors (PRRs), such as TLRs. TLR signaling influences multiple biological
processes including antigen presentation, cell survival, inflammation, and direct
antimicrobial responses. The latter enables macrophages to combat infectious
agents that persist within the intracellular environment. In this review, we
summarize our current understanding of TLR-inducible direct antimicrobial
responses that macrophages employ against bacterial pathogens, with a focus on
emerging evidence linking TLR signaling to reprogramming of mitochondrial
functions to enable the production of direct antimicrobial agents such as ROS and
itaconic acid. In addition, we describe other TLR-inducible antimicrobial
pathways, including autophagy/mitophagy, modulation of nutrient availability,
metal ion toxicity, reactive nitrogen species, immune GTPases (immunity-related
GTPases and guanylate-binding proteins), and antimicrobial peptides. We also
describe examples of mechanisms of evasion of such pathways by professional
intramacrophage pathogens, with a focus on Salmonella, Mycobacteria, and
Listeria. An understanding of how TLR-inducible direct antimicrobial responses
are regulated, as well as how bacterial pathogens subvert such pathways, may
provide new opportunities for manipulating host defence to combat infectious
diseases.
PMID- 29345057
TI - Sodium chloride inhibits IFN-gamma, but not IL-4, production by invariant NKT
cells.
AB - Invariant NKT (iNKT) cells are a distinct subset of T cells that exert Janus-like
functions in vivo by producing IFN-gamma and IL-4. Sodium chloride modulates the
functions of various immune cells, including conventional CD4+ T cells and
macrophages. However, it is not known whether sodium chloride affects iNKT cell
function, so we addressed this issue. Sodium chloride inhibited IFN-gamma, but
not IL-4, production by iNKT cells upon TCR or TCR-independent (IL-12 and IL-18)
stimulation in a dose-dependent manner. Consistently, sodium chloride reduced the
expression level of tbx21, but not gata-3, in iNKT cells stimulated with TCR
engagement or IL-12 + IL-18. Sodium chloride increased phosphorylated p38
expression in iNKT cells and inhibitors of p38, NFAT5, SGK1, and TCF-1 restored
IFN-gamma production by iNKT cells stimulated with sodium chloride and TCR
engagement. Furthermore, adoptive transfer of iNKT cells pretreated with sodium
chloride restored antibody-induced joint inflammation to a lesser extent than for
untreated iNKT cells in Jalpha18 knockout mice. These findings suggest that
sodium chloride inhibits IFN-gamma production by iNKT cells in TCR-dependent and
TCR-independent manners, which is dependent on p38, NFAT5, SGK1, and TCF-1. These
findings highlight the functional role of sodium chloride in iNKT cell-mediated
inflammatory diseases.
PMID- 29345058
TI - Frontline Science: Anti-PD-L1 protects against infection with common bacterial
pathogens after burn injury.
AB - Burn patients are susceptible to infections due, in part, to immune dysfunction.
Upregulation of programmed death-1 (PD-1) receptor on T cells and programmed cell
death ligand-1 (PD-L1) on myeloid cells contribute to immune dysfunction in
nonburn-related sepsis. We hypothesized that PD-1/PDL1 interactions contribute to
immune dysfunction after burn injury. To determine the impact of burn injury and
infection on PD-L1, PD-1 and costimulatory receptor expression by leukocytes and
its relationship to T cell functions. The efficacy of anti-PD-L1 antibody was
evaluated in a clinically relevant mouse model of burn injury and bacterial
infection. Mice underwent 35% scald burn followed by Pseudomonas aeruginosa or
Staphylococcus aureus infection on day 4 postburn. Anti-PD-L1 was administered on
day 3 postburn. Numbers and phenotype of leukocytes, plasma cytokine
concentrations, bacterial clearance, organ injury, and survival were assessed.
Burn injury and infection with P. aeruginosa caused a significant upregulation of
PD-L1 on myeloid cells, along with a decrease in T cell numbers and function,
significant multiorgan injury, and decreased survival. Treatment with anti-PD-L1
antibody improved bacterial clearance, reduced organ injury, and enhanced
survival during Pseudomonas burn wound infection. Furthermore, anti-PD-L1
effectively protected against multiorgan injury, and improved bacterial clearance
and survival following systemic S. aureus infection after burn injury. Blockade
of PD-1/PD-L1 interactions might represent a viable treatment to improve outcomes
among critically ill burn-injured subjects and increased leukocyte PD-L1
expression could serve as a valuable biomarker to select appropriate patients for
such treatment.
PMID- 29345059
TI - MicroRNA networks associated with active systemic juvenile idiopathic arthritis
regulate CD163 expression and anti-inflammatory functions in macrophages through
two distinct mechanisms.
AB - Systemic juvenile idiopathic arthritis (SJIA) is a severe childhood arthropathy
with features of autoinflammation. Monocytes and macrophages in SJIA have a
complex phenotype with both pro- and anti-inflammatory properties that combine
features of several well characterized in vitro conditions used to activate
macrophages. An important anti-inflammatory phenotype is expression of CD163, a
scavenger receptor that sequesters toxic pro-inflammatory complexes that is
highly expressed in both active SJIA and macrophage activation syndrome (MAS).
CD163 is most strongly up-regulated by IL-10 (M(IL-10)), and not by other
conditions that reflect features seen in SJIA monocytes such as M(LPS+IC).
MicroRNA plays key roles in integrating cellular signals such as those in
macrophage polarization, and as such we hypothesize microRNAs regulate macrophage
functional responses in SJIA including CD163 expression. We find that 2 microRNAs
previously found to be elevated in active SJIA, miR-125a-5p and miR-181c,
significantly reduced macrophage CD163 expression through 2 distinct mechanisms.
Neither microRNA was elevated in M(IL-10) with robust CD163 expression, but were
instead induced in M(LPS+IC) where they restricted CD163 mRNA expression. Mir-181
species directly targeted CD163 mRNA for degradation. In contrast, miR-125a-5p
functions indirectly, as transcriptome analysis of miR-125a-5p overexpression
identified "cytokine-cytokine receptor interactions" as the most significantly
repressed gene pathway, including decreased IL10RA, required for IL-10-mediated
CD163 expression. Finally, overexpression of miR-181c inhibited CD163 anti
inflammatory responses to hemoglobin or high mobility group box 1 (HMGB1)
complexes. Together, these data show that microRNA utilizes multiple mechanisms
to integrate well-characterized polarization phenotypes and regulate macrophage
functional properties seen in SJIA.
PMID- 29345060
TI - Porcine NK cells display features associated with antigen-presenting cells.
AB - NK cells are members of the innate immunity and play a central role in the
defense against viral infections and cancer development, but also contribute to
triggering and shaping adaptive immune responses. Human NK cells may express MHC
II and costimulatory molecules, including CD86, CD80, and OX40 ligand, which
allows them to stimulate the CD4+ T-cell response. In contrast, murine NK cells
do not express MHC II or costimulatory molecules. Upon activation, mouse NK cells
can acquire these molecules from dendritic cells (DCs) via intercellular membrane
transfer, which leads to suppression of DC-induced CD4+ T-cell responses rather
than stimulation of T-cell responses. Previous studies showed that porcine NK
cells can express MHC II molecules, but it was unknown if porcine NK cells also
express costimulatory molecules and whether NK cells may affect T-cell
proliferation. We found that primary porcine NK cells express functional MHC II
molecules and costimulatory CD80/86, particularly upon activation with IL-2/IL
12/IL-18, and that they are able to stimulate T-cell proliferation. In addition,
we show that porcine NK cells are able to internalize antigens derived from
killed target cells in an actin polymerization-dependent process. All together,
these results indicate that porcine NK cells possess properties associated with
APCs, which allows them to stimulate T-cell proliferation.
PMID- 29345061
TI - Monocyte subsets exhibit transcriptional plasticity and a shared response to
interferon in SIV-infected rhesus macaques.
AB - The progression to AIDS is influenced by changes in the biology of heterogeneous
monocyte subsets. Classical (CD14++CD16-), intermediate (CD14++CD16+), and
nonclassical (CD14+CD16++) monocytes may represent progressive stages of monocyte
maturation or disparate myeloid lineages with different turnover rates and
function. To investigate the relationship between monocyte subsets and the
response to SIV infection, we performed microarray analysis of monocyte subsets
in rhesus macaques at three time points: prior to SIV infection, 26 days
postinfection, and necropsy with AIDS. Genes with a 2-fold change between
monocyte subsets (2023 genes) or infection time points (424 genes) were selected.
We identify 172 genes differentially expressed among monocyte subsets in both
uninfected and SIV-infected animals. Classical monocytes express genes associated
with inflammatory responses and cell proliferation. Nonclassical monocytes
express genes associated with activation, immune effector functions, and cell
cycle inhibition. The classical and intermediate subsets are most similar at all
time points, and transcriptional similarity between intermediate and nonclassical
monocytes increases with AIDS. Cytosolic sensors of nucleic acids, restriction
factors, and IFN-stimulated genes are induced in all three subsets with AIDS. We
conclude that SIV infection alters the transcriptional relationship between
monocyte subsets and that the innate immune response to SIV infection is
conserved across monocyte subsets.
PMID- 29345062
TI - Trans-mission control in the urinary tract: Local cytokine regulation of monocyte
proliferation to combat infection.
PMID- 29345063
TI - Immunotherapy: It is not just for cancer anymore.
PMID- 29345064
TI - TLR8 ligation induces apoptosis of monocytic myeloid-derived suppressor cells.
AB - Myeloid-derived suppressor cells (MDSCs) accumulate in tumors and the peripheral
blood of cancer patients and demonstrate cancer-promoting activity across
multiple tumor types. A limited number of agents are known to impact MDSC
activity. TLR8 is expressed in myeloid cells. We investigated expression of TLR8
on MDSC and the effect of a TLR8 agonist, motolimod, on MDSC survival and
function. TLR8 was highly expressed in monocytic MDSC (mMDSC) but absent in
granulocytic MDSC (gMDSC). Treatment of human PBMC with motolimod reduced the
levels of mMDSC in volunteers and cancer donors versus control (P < 0.001).
Motolimod did not impact levels of gMDSC. The reduction of mMDSC was due to
induced cell death by TLR8 ligation. Pretreatment of PBMC with a FAS neutralizing
antibody inhibited motolimod-induced reduction of mMDSC (P < 0.001). Finally, we
demonstrated that mMDSC impeded IL-2 secretion by CD3/CD28-activated T cells; IL
2 secretion was partially restored when cells were cocultured with motolimod (142
+/- 36 pg/ml vs. 59 +/- 13 pg/ml; P = 0.03). There is increasing evidence that
MDSCs contribute to the progression of cancer by inhibiting tumor-directed T
cells. TLR8 agonists may synergize with cancer immunotherapeutic approaches to
enhance the antitumor effects of the adaptive immune response.
PMID- 29345065
TI - Fingolimod targets cerebral endothelial activation to block leukocyte recruitment
in the central nervous system.
AB - Fingolimod (FTY720), an immunomodulator, is approved as an oral treatment for
patients with relapsing forms of multiple sclerosis. Its effects are largely
attributed to its mechanism of selectively retaining lymphocytes in the lymph
nodes to reduce autoreactive T-cell recruitment in the CNS. In this study, we
investigated the therapeutic effect of FTY720 on an animal model of CNS
inflammation induced by intracerebral ventricle LPS injection. We found that
FTY720 treatment significantly prevented LPS-induced neutrophil recruitment in
the CNS by inhibiting leukocyte recruitment in cerebral microvessels.
Furthermore, FTY720 also inhibited the expressions of adhesion molecules on the
cerebral endothelium, but did not affect the expression levels of pro
inflammatory cytokines (TNF-alpha and IL-6) and chemokines (CXCL1 and CXCL2) in
the CNS parenchyma. The inhibition of endothelial activation was accompanied by
reduced phosphorylation of signaling molecules, including serine/threonine
specific protein kinase (Akt), STAT6, and nuclear factor-kappaB. This FTY720
attenuated inhibition of leukocyte recruitment and endothelial activation was
reversed by blocking the functions of sphingosine kinase 2 or sphingosine-1
phosphate receptor 1. Our study demonstrated, for the first time, that FTY720
directly inhibits the phosphorylation of multiple signaling molecules in
endothelial cells, thereby effectively blocking leukocyte recruitment in the CNS.
PMID- 29345066
TI - Protease activated-receptor 2 is necessary for neutrophil chemorepulsion induced
by trypsin, tryptase, or dipeptidyl peptidase IV.
AB - Compared to neutrophil chemoattractants, relatively little is known about the
mechanism neutrophils use to respond to chemorepellents. We previously found that
the soluble extracellular protein dipeptidyl peptidase IV (DPPIV) is a neutrophil
chemorepellent. In this report, we show that an inhibitor of the protease
activated receptor 2 (PAR2) blocks DPPIV-induced human neutrophil chemorepulsion,
and that PAR2 agonists such as trypsin, tryptase, 2f-LIGRL, SLIGKV, and AC55541
induce human neutrophil chemorepulsion. Several PAR2 agonists in turn block the
ability of the chemoattractant fMLP to attract neutrophils. Compared to
neutrophils from male and female C57BL/6 mice, neutrophils from male and female
mice lacking PAR2 are insensitive to the chemorepulsive effects of DPPIV or PAR2
agonists. Acute respiratory distress syndrome (ARDS) involves an insult-mediated
influx of neutrophils into the lungs. In a mouse model of ARDS, aspiration of
PAR2 agonists starting 24 h after an insult reduce neutrophil numbers in the
bronchoalveolar lavage (BAL) fluid, as well as the post-BAL lung tissue.
Together, these results indicate that the PAR2 receptor mediates DPPIV-induced
chemorepulsion, and that PAR2 agonists might be useful to induce neutrophil
chemorepulsion.
PMID- 29345067
TI - Supramolecular Gels Derived from the Salts of Variously Substituted Phenylacetic
Acid and Dicyclohexylamine: Design, Synthesis, Structures, and Dye Adsorption.
AB - A well-studied supramolecular synthon, namely, secondary ammonium monocarboxylate
(SAM), was exploited to generate a new series of organic salts derived from
variously substituted phenylacetic acid and dicyclohexylamine as potential low
molecular-weight gelators. As much as 25 % of the SAM salts under study were
gelators. The gels were characterized by rheology, and the morphology of the gel
networks was studied by high-resolution electron microscopy. Single-crystal and
powder XRD data were employed to study structure-property (gelation)
correlations. One of the gels could adsorb a hydrophobic dye (Nile Red) more
efficiently than that of a hydrophilic dye (Calcein) from dimethyl sulfoxide;
this might provide useful clues towards the development of stain-removing gels.
PMID- 29345068
TI - International Diabetes Federation 2017.
AB - Ann M. Carracher, Payal H. Marathe, and Kelly L. Close are of Close Concerns
(http://www.closeconcerns.com), a healthcare information company focused
exclusively on diabetes and obesity care. Close Concerns publishes Closer Look, a
periodical that brings together news and insights in these areas. Each month, the
Journal of Diabetes includes this News feature, in which Carracher, Marathe, and
Close review the latest developments relevant to researchers and clinicians.
PMID- 29345069
TI - Automation aided optimization of cloning, expression and purification of enzymes
of the bacterial sialic acid catabolic and sialylation pathways enzymes for
structural studies.
AB - The process of obtaining a well-expressing, soluble and correctly folded
constructs can be made easier and quicker by automating the optimization of
cloning, expression and purification. While there are many semiautomated
pipelines available for cloning, expression and purification, there is hardly any
pipeline that involves complete automation. Here, we achieve complete automation
of all the steps involved in cloning and in vivo expression screening. This is
demonstrated using 18 genes involved in sialic acid catabolism and the surface
sialylation pathway. Our main objective was to clone these genes into a His
tagged Gateway vector, followed by their small-scale expression optimization in
vivo. The constructs that showed best soluble expression were then selected for
purification studies and scaled up for crystallization studies. Our technique
allowed us to quickly find conditions for producing significant quantities of
soluble proteins in Escherichia coli, their large-scale purification and
successful crystallization of a number of these proteins. The method can be
implemented in other cases where one needs to screen a large number of
constructs, clones and expression vectors for successful recombinant production
of functional proteins.
PMID- 29345070
TI - Following one's scientific compass.
PMID- 29345071
TI - Detecting selection signatures on the X chromosome of the Chinese Debao pony.
AB - The X chromosome shows a special interaction between demographic factors and
genetic variation, and the analysis of X-linked genomic variation can therefore
provide insights into the unique effects of demography and selection on the horse
genome that cannot be readily detected by autosomal markers. Debao (DB) ponies
have experienced intense selective pressure for the development of their small
stature (<106 cm at adult height). To identify selective sweeps on the X
chromosome of the DB pony, we performed a genome-wide scan of three Chinese horse
breeds using an Equine SNP70 BeadChip. Using Yili and Mongolian horses (>134 cm
at adult height) as reference groups, both FST and XP-EHH revealed that five
regions on the X chromosome were under strong selection, resulting in 95
overlapping genes. Seven of these genes, SMS, PHEX, ACSL4, CHRDL1, CACNA1F, DKC1
and CDKL5, are involved in bone development, growth hormone secretion and fat
deposition. The region showing the strongest selection pressure was located at
the position of 86.6-87.5 Mb. The subsequent genome-wide association analysis of
the adult height of three Chinese horse breeds detected the two most significant
SNPs in the same region, and these two SNPs overlapped with the gene CHRDL1. As a
member of the bone morphogenetic protein (BMP) superfamily, CHRDL1 antagonizes
the function of BMP4 and plays an important role in embryonic bone formation and
cartilage generation. Our results provide new insights into the X-linked
selection in Chinese Debao pony.
PMID- 29345072
TI - Genetic monitoring of horses in the Czech Republic: A large-scale study with a
focus on the Czech autochthonous breeds.
AB - We propose the first comprehensive in-depth study monitoring horses in the Czech
Republic. We scanned 9,289 animals from 44 populations for 17 equine STRs. Other
equids analysed involved Equus przewalskii and Equus asinus. The total of 228
different alleles were detected, with the mean number of 13.4 per locus. The
highest allelic richness (AR) was found in the Welsh Part Bred (6.01), followed
by the Camargue (5.93) and Czech Sport Pony (5.91), whereas the Friesian
exhibited the lowest AR (3.06). Interpopulation differences explained
approximately nine per cent of the total genetic diversity. Reynold's genetic
distance ranged from 0.003 between the Czech Warmblood and the Slovak Warmblood
to 0.404 between the Friesian and donkeys. Close genetic proximity between the
Silesian Noriker and Noriker was revealed. The Moravian Warmblood was better
differentiated and more distant from the Czech Warmblood than the Kinsky Horse
and retained the original genes of the old Austro-Hungarian tribes. A high gene
flow level and a lack of genetic structure were found in the seven studied
populations. Despite the historical bottlenecks and previous inbreeding, the
Czech-Moravian Belgian Horse, Hucul, Old Kladruber Horse and Silesian Noriker did
not suffer a serious loss of genetic diversity due to genetic drift/low effective
population size. A NeighborNet dendrogram revealed breeds not classified in their
groups according to the nomenclature (the Friesian, Hafling and Merens).
PMID- 29345073
TI - Improving accuracy of genomic prediction in Brangus cattle by adding animals with
imputed low-density SNP genotypes.
AB - Reliable genomic prediction of breeding values for quantitative traits requires
the availability of sufficient number of animals with genotypes and phenotypes in
the training set. As of 31 October 2016, there were 3,797 Brangus animals with
genotypes and phenotypes. These Brangus animals were genotyped using different
commercial SNP chips. Of them, the largest group consisted of 1,535 animals
genotyped by the GGP-LDV4 SNP chip. The remaining 2,262 genotypes were imputed to
the SNP content of the GGP-LDV4 chip, so that the number of animals available for
training the genomic prediction models was more than doubled. The present study
showed that the pooling of animals with both original or imputed 40K SNP
genotypes substantially increased genomic prediction accuracies on the ten
traits. By supplementing imputed genotypes, the relative gains in genomic
prediction accuracies on estimated breeding values (EBV) were from 12.60% to
31.27%, and the relative gain in genomic prediction accuracies on de-regressed
EBV was slightly small (i.e. 0.87%-18.75%). The present study also compared the
performance of five genomic prediction models and two cross-validation methods.
The five genomic models predicted EBV and de-regressed EBV of the ten traits
similarly well. Of the two cross-validation methods, leave-one-out cross
validation maximized the number of animals at the stage of training for genomic
prediction. Genomic prediction accuracy (GPA) on the ten quantitative traits was
validated in 1,106 newly genotyped Brangus animals based on the SNP effects
estimated in the previous set of 3,797 Brangus animals, and they were slightly
lower than GPA in the original data. The present study was the first to leverage
currently available genotype and phenotype resources in order to harness genomic
prediction in Brangus beef cattle.
PMID- 29345074
TI - A century later.
PMID- 29345075
TI - Genetic analyses of linear profiling data on 3-year-old Swedish Warmblood horses.
AB - A linear profiling protocol was introduced in 2013 at tests for 3-year-old
Swedish Warmblood horses. In this protocol, traits are subjectively described on
a nine-point linear scale from one biological extreme to the other. This
complements the traditional scoring where horses are evaluated in relation to the
breeding objective. This study aimed to investigate the suitability of the linear
information for genetic evaluation. Data on 22 conformation traits, 17 movement
traits, 14 jumping traits and one temperament trait from 3,410 horses tested
between 2013 and 2016 were analysed using an animal model. For conformation
traits, the heritabilities ranged from 0.10 for description of hock joint from
behind to 0.52 for shape of the neck. For movement traits, the highest
heritability (0.54) was estimated for elasticity in trot and the lowest (0.08)
for energy in walk. The heritabilities for jumping traits ranged from 0.05 for
the ability to focus on the assignment to 0.57 for scope. Genetic correlations
between linear traits and corresponding traditionally scored traits were strong (
0.37 to in many cases <-0.9). The results show that the linear information is
suitable for genetic evaluation and can be a useful tool for breeders.
PMID- 29345076
TI - Rice-farming care for the elderly people with cognitive impairment in Japan: a
case series.
PMID- 29345077
TI - Gender difference in the association and presentation of visual hallucinations in
dementia with Lewy bodies: statistical and methodological issues.
PMID- 29345078
TI - Re: An investigation of public attitudes towards dementia in Bristol and South
Gloucestershire using an online version of the Approaches to Dementia
Questionnaire.
PMID- 29345079
TI - Acreemagnosia (loss of financial knowledge): a symptom of functional and
cognitive loss in frail elderly.
PMID- 29345081
TI - Screening for latent tuberculosis infection among patients with rheumatoid
arthritis in the era of biologics and targeted synthetic disease-modifying anti
rheumatic drugs in India, a high-burden TB country: The importance of Mantoux and
Quantiferon-TB Gold tests.
AB - AIM: To test the validity of an augmented tuberculosis skin test (a-TST) combined
with Quantiferon TB-gold(r) (QFTG) test for the screening of latent tuberculosis
infection (LTBI) in patients with rheumatoid arthritis (RA) being considered for
treatment with biologic disease-modifying anti-rheumatic drugs or targeted
synthetic disease-modifying anti-rheumatic drugs. METHOD: Standard TST using 1
tuberculin unit (TU) of purified protein derivative (PPD, RT23 strain) was
carried out. If the positivity was less as compared to the general population,
then a-TST using 10 TU PPD was employed. Simultaneously, QFTG test was also
performed. RESULTS: Using standard TST, 6/44 (13.6%), patients were positive
compared to the reported figures of ~ 40% of the general population; 38 of the
remaining TST-negative patients were then given an a-TST with 10 TU PPD; eight of
them dropped out. Of the remaining 30 patients, eight (26.6%) were positive.
Another 70 patients tested directly with a-TST; 22 (31.4%) were found positive.
Thus, of a total of 100 patients tested with a-TST, 30 (30%) were positive. In 54
a-TST negative patients, QFTG was done; seven (13%) were positive. Thus, in
combined a-TST with QFTG, 43% of the RA patients were found positive, suggestive
of the presence of LTBI. CONCLUSION: Combined a-TST with QFTG testing gave 43%
positivity among RA patients, which is close to the reported ~ 40% Mantoux
positivity in the general population. Therefore, this method for the screening of
LTBI in Indian patients with RA being considered for tumor necrosis factor alpha
treatment could be satisfactory for offsetting TB flare. It may apply to other
high-burden TB countries around the world.
PMID- 29345080
TI - Environmental adaptation and vertical dissemination of ESBL-/pAmpC-producing
Escherichia coli in an integrated broiler production chain in the absence of an
antibiotic treatment.
AB - High prevalence numbers of extended-spectrum beta-lactamase- (ESBL-)/plasmid
mediated AmpC beta-lactamase- (pAmpC-) producing Escherichia coli in broiler
chicken and their distribution along the broiler production chain is an ongoing
problem in food production. We, therefore, investigated resistant isolates along
the broiler production chain to determine whether there is a constantly occurring
direct vertical transmission of the ESBL-/pAmpC-producing E. coli from the parent
flocks to their offspring or not. We, furthermore, analysed the isolates
concerning the occurrence of virulence factors and their ability to form biofilms
to estimate their potential to effectively colonize broiler chickens and/or
persist and survive in the environment of the broiler production facilities.
Using whole genome sequencing, we could show that ESBL-/pAmpC-producing E. coli
were likely transferred in a step-wise process along the broiler production chain
but not directly from the parent flock to the fattening flock with every single
batch of offspring chickens. Additionally, resistant E. coli strains showing an
extraintestinal pathogenic genotype as well as high numbers of virulence
associated genes including the production of curli fibres and cellulose have high
capabilities to persist and spread in the broiler production chain.
PMID- 29345082
TI - How should we respond to cannabis-impaired driving?
PMID- 29345083
TI - Brief workshops to teach drug and alcohol first aid: A pilot evaluation study.
AB - INTRODUCTION AND AIMS: Health and community service workers frequently encounter
people with alcohol and other drug (AOD) problems in the course of their work,
yet few have had training on how to respond effectively. A Drug and Alcohol First
Aid workshop was developed by Lyndon, a non-government organisation treatment
provider, and delivered to community and health sector workers and the general
public. It presented evidence-based information regarding AOD use and harm
reduction and treatment options. A pilot evaluation of the workshop was conducted
to assess changes in participants' knowledge about AOD, methods of responding to
use and attitudes towards individuals who use AOD, over a 3 month period. DESIGN
AND METHODS: A self-report evaluation survey was developed and administered to
workshop participants at three time points: before (T1), immediately after (T2)
and 3 months after the workshop (T3). Paired samples t-tests examined changes in
knowledge, role adequacy, motivation and personal views. RESULTS: A total of 142
participants completed the T1 survey, 184 completed the T2 survey and 98
completed the T3 survey. Between T1 and T2, there were significant increases in
scores for knowledge and role adequacy, indicating significant improvements in
these areas. No significant differences were found for motivation and personal
views. At T3, knowledge and role adequacy scores remained significantly higher
than at baseline. DISCUSSION AND CONCLUSIONS: Drug and Alcohol First Aid appears
to be a viable initiative to improve AOD-related knowledge and role adequacy.
However, alternative strategies may be required to shift negative attitudes
towards individuals who use AOD. [Kostadinov VR, Roche AM, McEntee A, Allan JM,
Meumann NR, McLaughlin LL. Brief workshops to teach drug and alcohol first aid: A
pilot evaluation study. Drug Alcohol Rev 2018;37:23-27].
PMID- 29345084
TI - The lived experience of autologous stem cell-transplanted patients: Post
transplantation and before discharge.
AB - AIMS AND OBJECTIVES: To explore the lived experience of the patients post
haematopoietic stem cell transplantation and specifically after engraftment and
before discharge. BACKGROUND: Patients post-stem cell transplantation experience
significant changes in all life aspects. Previous studies carried out by other
researchers focused mainly on the postdischarge experience, where patients
reported their perceptions that have always been affected by the life post
transplantation and influenced by their surroundings. The lived experience of
patients, specifically after engraftment and prior to discharge (the "transition"
phase), has not been adequately explored in the literature. Doing so might
provide greater insight into the cause of change post-haematopoietic stem cell
transplantation. DESIGN: This study is a phenomenological description of the
participants' perception about their lived experience post-haematopoietic stem
cell transplantation. The study used Giorgi's method of analysis. METHODS:
Through purposive sampling, 15 post-haematopoietic stem cell transplantation
patients were recruited. Data were collected by individual interviews. Data were
then analysed based on Giorgi's method of analysis to reveal the meaning of a
phenomenon as experienced through the identification of essential themes.
RESULTS: The analysis process revealed 12 core themes covered by four categories
that detailed patients lived experience post-haematopoietic stem cell
transplantation. The four categories were general transplant experience, effects
of transplantation, factors of stress alleviation and finally life post
transplantation. CONCLUSION: This study showed how the haematopoietic stem cell
transplantation affected the patients' physical, psychological and spiritual well
being. Transplantation also impacted on the patients' way of thinking and
perception of life. Attending to patients' needs during transplantation might
help to alleviate the severity of the effects and therefore improve experience.
RELEVANCE TO CLINICAL PRACTICE: Comprehensive information about transplantation
needs to be provided over different intervals and at different occasions. The
role of the haematopoietic stem cell transplantation coordinators is important,
and their communication skills and knowledge were found to be significant in
patients' preparation and decision-making. As healthcare providers usually attend
to only the patients' physical and psychological needs, spirituality was found to
play an important role in maintaining morale and making sense of the meaning of
life.
PMID- 29345085
TI - Effects of ultrasonication variables on the activity and properties of alpha
amylase preparation.
AB - Recently, ultrasound was demonstrated to increase enzyme activity in food
industry. In most studies, an enzyme-substrate mixture was ultrasonicated. Very
little is reported on the ultrasonication of enzyme preparation; the effects of
ultrasonication variables on the enzyme activity and properties remained unclear.
In this study, an alpha-amylase preparation was ultrasonicated under different
conditions. At the ultrasonic frequency, power, temperature, and time of 20 kHz,
25 W/mL, 30 degrees C, and 75 s, respectively, the secondary structure of the
alpha-amylase was changed and that improved the catalytic activity by 47% over
the control. The optimal temperature and pH of the alpha-amylase preparation did
not change under the ultrasonic treatment. In addition, ultrasonic treatment
increased kinetic parameters of the alpha-amylase including maximal velocity Vmax
, Michaelis constant Km , turnover number Kcat , and catalytic specificity
constant Kcat /Km . Nevertheless, the ultrasonicated alpha-amylase had lower
thermal inactivation rate constant and half-life value than the nonultrasonicated
enzyme. Ultrasonic treatment can be considered as a novel solution for
improvement in enzyme activity. (c) 2018 American Institute of Chemical Engineers
Biotechnol. Prog., 34:702-710, 2018.
PMID- 29345086
TI - Safety of dipyrone (metamizole) in children-What's the risk of agranulocytosis?
PMID- 29345087
TI - In this issue: February 2018.
PMID- 29345088
TI - Retraction.
AB - : 'The association of hypotension with the insertion of an abdominal retractor
during lower abdominal surgery in pediatric patients: a retrospective
observational study' by Rika Nakayama, Takahiro Mihara, Yoshihisa Miyamoto & Koui
Ka.1 The above article from Pediatric Anesthesia, published online on July 7,
2015 in Wiley Online Library (http://wileyonlinelibrary.com) has been retracted
by agreement between the authors, the Journal Editor in Chief, Andrew Davidson,
and John Wiley & Sons Ltd. The retraction has been agreed following a review of
the study data by the authors, which found that cases not satisfying the
inclusion criteria were included and that there were data collection errors with
respect to the patients' ages and sexes. As a result, the authors judged that the
reproducibility of the results could not be guaranteed and have requested
retraction. REFERENCE: Nakayama R, Mihara T, Miyamoto Y, Ka K. The association of
hypotension with the insertion of an abdominal retractor during lower abdominal
surgery in pediatric patients: a retrospective observational study. Pediatr
Anesth. 2015;25:824-828. https://doi.org/10.1111/pan.12656.
PMID- 29345089
TI - Increased lactate load of older red blood cell preparations increases blood
lactate concentrations in infants during cardiac surgery.
PMID- 29345090
TI - Comment on Chiem J, Ivanova I, Jimenez N. Anaphylactic reaction to tranexamic
acid in an adolescent undergoing posterior spinal fusion.
PMID- 29345091
TI - The responses of microbial temperature relationships to seasonal change and
winter warming in a temperate grassland.
AB - Microorganisms dominate the decomposition of organic matter and their activities
are strongly influenced by temperature. As the carbon (C) flux from soil to the
atmosphere due to microbial activity is substantial, understanding temperature
relationships of microbial processes is critical. It has been shown that
microbial temperature relationships in soil correlate with the climate, and
microorganisms in field experiments become more warm-tolerant in response to
chronic warming. It is also known that microbial temperature relationships
reflect the seasons in aquatic ecosystems, but to date this has not been
investigated in soil. Although climate change predictions suggest that
temperatures will be mostly affected during winter in temperate ecosystems, no
assessments exist of the responses of microbial temperature relationships to
winter warming. We investigated the responses of the temperature relationships of
bacterial growth, fungal growth, and respiration in a temperate grassland to
seasonal change, and to 2 years' winter warming. The warming treatments increased
winter soil temperatures by 5-6 degrees C, corresponding to 3 degrees C warming
of the mean annual temperature. Microbial temperature relationships and
temperature sensitivities (Q10 ) could be accurately established, but did not
respond to winter warming or to seasonal temperature change, despite significant
shifts in the microbial community structure. The lack of response to winter
warming that we demonstrate, and the strong response to chronic warming
treatments previously shown, together suggest that it is the peak annual soil
temperature that influences the microbial temperature relationships, and that
temperatures during colder seasons will have little impact. Thus, mean annual
temperatures are poor predictors for microbial temperature relationships.
Instead, the intensity of summer heat-spells in temperate systems is likely to
shape the microbial temperature relationships that govern the soil-atmosphere C
exchange.
PMID- 29345092
TI - Known unknowns: Examining the burden of neurocognitive impairment in the end
stage renal failure population.
AB - The burden of neurocognitive impairment (NCI) in patients receiving maintenance
dialysis represents a spectrum of deficits across multiple cognitive domains that
are associated with hospitalization, reduced quality-of-life, mortality and
forced decision-making around dialysis withdrawal. Point prevalence data suggest
that dialysis patients manifest NCI at rates 3- to 5-fold higher than the general
population, with executive function the most commonly affected cognitive domain.
The unique physiology of the renal failure state and maintenance dialysis appears
to drive an excess of vascular dementia subtype compared to the general
population where classical Alzheimer's disease predominates. Despite the absence
of evidence-based cost-effective therapies for NCI, detecting it in this
population creates opportunity to proactively personalize care through education,
supported decision making and targeted communication strategies to cover specific
areas of deficit and help define goals of care. This review discusses NCI in the
dialysis setting, including developments in the definition of neurocognitive
impairment, dialysis-specific epidemiology across modalities, screening
strategies and opportunities for dialysis providers in this space.
PMID- 29345094
TI - But is it 'evidence'?
PMID- 29345093
TI - Rapid fabrication of detachable three-dimensional tissues by layering of cell
sheets with heating centrifuge.
AB - Confluent cultured cells on a temperature-responsive culture dish can be
harvested as an intact cell sheet by decreasing temperature below 32 degrees C. A
three-dimensional (3-D) tissue can be fabricated by the layering of cell sheets.
A resulting 3-D multilayered cell sheet-tissue on a temperature-responsive
culture dish can be also harvested without any damage by only temperature
decreasing. For shortening the fabrication time of the 3-D multilayered
constructs, we attempted to layer cell sheets on a temperature-responsive culture
dish with centrifugation. However, when a cell sheet was attached to the culture
surface with a conventional centrifuge at 22-23 degrees C, the cell sheet hardly
adhere to the surface due to its noncell adhesiveness. Therefore, in this study,
we have developed a heating centrifuge. In centrifugation (55g) at 36-37 degrees
C, the cell sheet adhered tightly within 5 min to the dish without significant
cell damage. Additionally, centrifugation accelerated the cell sheet-layering
process. The heating centrifugation shortened the fabrication time by one-fifth
compared to a multilayer tissue fabrication without centrifugation. Furthermore,
the multilayered constructs were finally detached from the dishes by decreasing
temperature. This rapid tissue-fabrication method will be used as a valuable tool
in the field of tissue engineering and regenerative therapy. (c) 2018 American
Institute of Chemical Engineers Biotechnol. Prog., 34:692-701, 2018.
PMID- 29345095
TI - The term will survive.
PMID- 29345096
TI - Psychiatric sequelae of corticosteroid use in hematology in Australia: A
qualitative study.
AB - Despite widespread steroid usage for treating hematological conditions, minimal
attention focuses on associated psychiatric side-effects. In the present study,
we examined hematology patients' experiences of high-dose steroid treatment. This
was undertaken by the use of a qualitative, descriptive design, which included
convenience sampling and the inductive, cyclic, and constant comparative thematic
analysis of interview transcripts. Eighteen patients participated, who were
diagnosed with lymphoma, myeloma, leukemia, or idiopathic thrombocytopenia
purpura. Four themes emerged: side-effects, misattribution of cause, self
management, and fragmented information. The study results revealed that
hematology patients administered steroids can experience negligible to extensive
erratic side-effects, with severe adverse repercussions. Psychological reactions
to steroids are often misattributed. Patients mostly self-manage adverse effects
experienced and receive only fragmented preparatory information, often not
understanding steroid side-effects. Nurses could provide helpful "in the moment"
education for inpatients who misunderstood steroid-related adverse effects, such
as aggressive urges. Adverse repercussions for family were occasionally evident.
Education, support, and ongoing care for patients experiencing adverse steroid
side-effects are inadequate. Health professionals need to develop patient- and
family-centered educational resources for potential, unpredictable, and usually
adverse steroid side-effects.
PMID- 29345097
TI - The diagnostic value of the functional lumen imaging probe versus high-resolution
anorectal manometry in patients with fecal incontinence.
AB - BACKGROUND: The functional lumen imaging probe (EndoFLIP(r) ) is a new technology
that measures the distensibility of the anal canal represented by the anal
distensibility index. The aims of this study were (i) to compare the anal
distensibility index to anal pressure in a cohort of patients with fecal
incontinence (FI) and (ii) to compare the diagnostic value of the EndoFLIP(r) to
that of high-resolution anorectal manometry (HRAM) in the same cohort of
patients. METHODS: Eighty-three consecutive patients with FI who underwent
EndoFLIP(r) and HRAM assessments were enrolled. The diagnostic value of the
EndoFLIP(r) was compared to that of HRAM and agreement between EndoFLIP(r) and
HRAM data was assessed. KEY RESULTS: More than 70% of the patients diagnosed with
anal deficiency at rest and/or during voluntary contractions by HRAM had the same
diagnosis using the EndoFLIP(r) . Two patients with higher distensibility indexes
at rest had normal anal resting pressures. Sixteen patients with a normal
EndoFLIP(r) index (ie, normal distensibility index at rest and during voluntary
contractions) had an abnormal HRAM result. Seven of these 16 patients (44%) had
no sphincter lesion or neuropathic disorder that could explain an abnormal anal
sphincter function. CONCLUSIONS & INFERENCES: We demonstrated that the anal
distensibility index and HRAM results are largely in agreement. We did, however,
identify several discrepancies between the two techniques, indicating that they
may be complementary.
PMID- 29345098
TI - Influence of maternal obesity on fetal growth at different periods of pregnancies
with normal glucose tolerance.
AB - AIM: We aimed to examine the influence of maternal obesity on fetal growth in
utero at different periods of pregnancies with normal glucose tolerance. METHODS:
A retrospective cohort study on 356 pregnant women with normal glucose tolerance
was conducted. The women were categorized by pre-pregnancy body mass index (BMI)
as obese (OB; BMI >= 25.0 kg/m2 ) or non-obese (n-OB). Z-scores of the fetal
abdominal circumference (AC) and the rate of fetal macrosomia (AC >= 90th
percentile) at 19, 30, and 36 gestational weeks (GW) were compared between the
two groups. Maternal demographics (age, parity, height, pre-pregnancy BMI,
history of prior large-for-gestational-age delivery) were compared between the
pregnancies with and without fetal macrosomia at each gestational age. Multiple
logistic regression analysis was performed to determine the independent risk
factors for fetal macrosomia. RESULTS: Birthweights of the neonates were
significantly higher in the OB group. Z-scores of the fetal AC were significantly
higher in the OB group at 30 and 36 GW, while no significant difference was found
at 19 GW. The rates of fetal macrosomia in the OB group were also higher at 30
and 36 GW, while maternal obesity was not associated with fetal macrosomia at 19
GW. Pre-pregnancy BMI was detected as the independent predictor of fetal
macrosomia at 30 GW (odds ratio, 1.19 [95% CI]) and 36 GW (odds ratio, 1.13 [95%
CI]). CONCLUSION: Maternal pre-pregnancy obesity has a promoting effect on fetal
growth from the third trimester through birth.
PMID- 29345099
TI - Aortic versus carotid intima-media thickness and impact of aortic valve disease.
AB - BACKGROUND AND AIMS: Intima-media thickness is a marker for atherosclerosis but
is also influenced by shear stress and flow. We evaluated the relation between
intima-media thickness of the descending aorta (AoIMT) and the common carotid
artery (CIMT) in patients with and without severe aortic valve disease (sAVD).
METHODS: A total of 310 patients (233 with sAVD, 77 without) were examined with
regard to AoIMT and CIMT using transesophageal echocardiography and carotid
ultrasound, respectively, before valvular and/or aortic surgery. Digitally stored
B-mode images were used for semiautomatic AoIMT and CIMT measurements. RESULTS:
There were no significant differences in patients with or without sAVD with
regard to AoIMT (1.35 +/- 0.31 vs. 1.35 +/- 0.33 mm) or CIMT (0.80 +/- 0.15 vs.
0.78 +/- 0.16 mm). The correlations between AoIMT and CIMT were r = 0.29 in
patients with and r = 0.51 in patients without sAVD, and the difference between
these correlations was significant (P<0.05). In multivariate regression, age was
the main determinant for AoIMT and CIMT in both groups, further in sAVD, the
aortic mean pressure gradient (Pmean ) was a determinant of AoIMT, but not of
CIMT. CONCLUSIONS: The correlation between CIMT and AoIMT is weaker in patients
with sAVD compared to those without sAVD. Pmean is also a significant predictor
of AoIMT, but not of CIMT. This implies that, in addition to the atherosclerotic
process, turbulent aortic flow or altered blood flow helicity created by large
stroke volumes and diastolic flow reversal or high-velocity jets, affect the
intima-media of the descending aorta and common carotid artery differently.
PMID- 29345100
TI - Relationship between orthodox and traditional medical practitioners in the
transmission of traditional medical knowledge in Nigeria.
AB - BACKGROUND: The problem of incomplete transmission of traditional medical
knowledge to the younger generation is of concern to information professionals
especially in developing countries where most rural communities depend on
traditional medicine for primary health care. OBJECTIVE: The purpose of this
study was to investigate the collaboration between orthodox and traditional
medical practitioners as well as the implication of the collaboration for
transmission of traditional medical knowledge in Nigeria. METHOD: Eighteen
communities were purposively selected from six states in south-western Nigeria.
Snowball technique was used in selecting 110 traditional medical practitioners.
Three key informant interviews and two focus group discussion sessions were
conducted in each state. Data were analysed thematically. DISCUSSION: Results
showed the existence of a low level of collaboration mainly in the form of
patient referrals which were not performed officially and mostly one sided. This
was attributed to the negative perception of traditional medicine by orthodox
practitioners and the failure of government to give traditional medicine its due
recognition. This was reportedly responsible for the lack of interest by children
of traditional medical practitioners to acquire traditional medical knowledge.
CONCLUSION: The study recommends inclusion of traditional medicine in the health
policy and educational curriculum from the basic level.
PMID- 29345101
TI - A Pdgf-cCreERT2 knock-in mouse model for tracing PDGF-C cell lineages during
development.
AB - PDGF-C, a member of the platelet-derived growth factor (PDGF) family, plays
important roles in the development of craniofacial structures, the neural system,
the vascular system, and tumors. PDGF-C could also be required for the regulation
of certain types of stem or progenitor cells as suggested by its expression in
the regions where these cells are located. To further characterize the role of
PDGF-C in development, we generated a Pdgf-cCreERT2 mouse strain, in which a
tamoxifen-inducible Cre (CreERT2) cDNA was specifically targeted into the Pdgf-c
genomic locus and controlled by the endogenous Pdgf-c regulatory elements. We
also showed that Cre activity in this mouse strain could be specifically induced
by tamoxifen, which allowed the fate of PDGF-C-expressing cells to be traced at
various stages of development. Using this model system, we demonstrated for the
first time that PDGF-C-expressing cells could be multipotent, generating multiple
cell lineages required for the formation of the cerebellum. Therefore, the Pdgf
cCreERT2 mouse strain generated in this study will be a valuable transgenic tool
for exploring the function of PDGF-C in development and stem cell biology.
PMID- 29345102
TI - The mycobiota of the sand fly Phlebotomus perniciosus: Involvement of yeast
symbionts in uric acid metabolism.
AB - The knowledge of the fungal mycobiota of arthropods, including the vectors of
human and animal diseases, is still limited. Here, the mycobiota associated with
the sand fly Phlebotomus perniciosus, the main vector of leishmaniasis in the
western Mediterranean area, by a culture-dependent approach (microbiological
analyses and sequencing of the 26S rRNA gene), internal transcribed spacer (ITS)
rRNA amplicon-based next-generation sequencing, fluorescence in situ
hybridisation (FISH), and genome sequencing of the dominant yeast species was
investigated. The dominant species was Meyerozyma guilliermondii, known for its
biotechnological applications. The focus was on this yeast and its prevalence in
adults, pupae and larvae of reared sand flies (overall prevalence: 57.5%) and of
field-collected individuals (overall prevalence: 9%) was investigated. Using
whole-mount FISH and microscopic examination, it was further showed that M.
guilliermondii colonizes the midgut of females, males and larvae and the distal
part of Malpighian tubules of female sand flies, suggesting a possible role in
urate degradation. Finally, the sequencing and analysis of the genome of M.
guilliermondii allowed predicting the complete uric acid degradation pathway,
suggesting that the yeast could contribute to the removal of the excess of
nitrogenous wastes after the blood meal of the insect host.
PMID- 29345103
TI - Incidence of Common Cancers in Users of Antimuscarinic Medications for Overactive
Bladder: A Danish Nationwide Cohort Study.
AB - The purpose of this study was to estimate the incidence rate (IR) of 10 common
cancers in new users of antimuscarinic overactive bladder (OAB) medications. We
conducted a cohort study using data recorded in Danish registers for patients
newly exposed to the OAB drugs, darifenacin, fesoterodine, oxybutynin,
solifenacin, tolterodine or trospium in years 2004-2012, aged >=18 years and
without cancer before treatment initiation. We estimated IRs for each study
cancer (bladder, breast, colorectal, lung, melanoma, non-Hodgkin lymphoma,
pancreas, prostate, renal and uterine), standardised by age and sex and explored
IR trends over time since treatment initiation. For all cancer analyses, only the
first incident targeted cancer was considered. Of 72,917 patients (60% women;
mean age at treatment start: 66 years), 3475 developed a study cancer during
259,072 person-years of follow-up. The most common study cancers were prostate
(48.1% of study cancers in men), breast (40.0% of study cancers in women) and
lung (15.4% of all study cancers). The overall standardised study cancer IR was
5.4 per 1000 person-years (95% confidence interval, 5.3-5.6); IRs were similar
across individual OAB drugs. The standardised IRs for bladder and prostate
cancers, which have symptoms in common with OAB, were highest in the first 6
months of treatment initiation and lower thereafter. In contrast, IRs for other
study cancers were nearly constant during follow-up. Cancer IRs did not vary
substantially by individual OAB drug. Protopathic bias is a plausible explanation
for the higher rates of bladder and prostate cancers observed soon after starting
OAB drug treatment.
PMID- 29345104
TI - A Self-Growing Strategy for Large-Scale Crystal Assembly Tubes.
AB - Assembled tubular materials have attracted widespread attention due to their
potential applications in catalysis, bionics, and optic-electronics. Many
versatile methods, including template assistance and self-assembly, have been
developed for fabrication of tubular materials. Here we demonstrate a self
growing strategy to prepare large-scale crystal assembly tubes. Addition of the
template and the need for the sophisticated equipment are avoided with this
method. The sidewall of the tubes is composed of a layer of polyhedral crystals
that are connected together through grain coalescence. We demonstrate that the
assembled tubular structure is obtained by the synergetic effect of the
passivation layer and the dissolution-recrystallization process. This facile one
step strategy and the formation mechanism will offer guidance for fabrication of
new superstructures.
PMID- 29345105
TI - OsGATA7 modulates brassinosteroids-mediated growth regulation and influences
architecture and grain shape.
PMID- 29345106
TI - National study of the nutritional status of Korean older adults with dementia who
are living in long-term care settings.
AB - AIM: To evaluate the nutritional status of older adults with dementia who were
living in long-term care settings. METHODS: As a secondary analysis, this study
used the data from the Nationwide Survey on Dementia Care in Korea that was
conducted between December 1, 2010, and August 31, 2011, which surveyed 3472
older adults with dementia, aged >=60 years (mean age: 81.24 years), who were
residing in 248 randomly selected long-term care settings in South Korea. Twenty
three different variables that related to the participants' demographics,
diseases, and functional and nutritional characteristics were selected. The
nutritional status was assessed by using the Mini Nutritional Assessment (MNA).
Descriptive statistics, an ANOVA, and a chi-squared test were used to analyze the
data. RESULTS: The mean MNA score of the participants was 17.90. The malnutrition
rate was 38.4% (n = 1333), with 54.7% (n = 1900) of the participants at risk for
malnutrition. The largest population with malnutrition resided in long-term care
hospitals (47.9%), followed by nursing homes (34.1%), and group homes (25.9%).
Being older and female, while exhibiting higher cognitive impairment, more
neuropsychiatric symptoms, higher functional dependency, and a higher number of
disabilities, were associated with poor nutritional status. CONCLUSION: The
nutritional status of older adults with dementia who were living in long-term
care settings in South Korea was poor and associated with multiple factors.
Paying special attention to recognizing, assessing, preventing, and treating
malnutrition in this population is necessary.
PMID- 29345107
TI - Introduction to methodology of dose-response meta-analysis for binary outcome:
With application on software.
AB - OBJECTIVE: Dose-response meta-analysis (DRMA) is widely applied to investigate
the dose-specific relationship between independent and dependent variables. Such
methods have been in use for over 30 years and are increasingly employed in
healthcare and clinical decision-making. In this article, we give an overview of
the methodology used in DRMA. METHODS: We summarize the commonly used regression
model and the pooled method in DRMA. We also use an example to illustrate how to
employ a DRMA by these methods. RESULTS: Five regression models, linear
regression, piecewise regression, natural polynomial regression, fractional
polynomial regression, and restricted cubic spline regression, were illustrated
in this article to fit the dose-response relationship. And two types of pooling
approaches, that is, one-stage approach and two-stage approach are illustrated to
pool the dose-response relationship across studies. The example showed similar
results among these models. CONCLUSION: Several dose-response meta-analysis
methods can be used for investigating the relationship between exposure level and
the risk of an outcome. However the methodology of DRMA still needs to be
improved.
PMID- 29345108
TI - High neutrophil-to-lymphocyte ratio predicts poor prognosis in patients with
squamous cell carcinoma of the head and neck treated with definitive
chemoradiotherapy.
AB - AIM: To evaluate the role of neutrophil-to-lymphocyte ratio as a prognostic
marker in squamous cell carcinoma of the head and neck treated with definitive
chemoradiotherapy. METHODS: A retrospective chart review was performed on
patients presenting to our service between 2001 and 2014. Overall survival (OS)
and progression-free survival (PFS) were calculated using Kaplan-Meier estimates.
The association between neutrophil-to-lymphocyte ratio and survival was analyzed
by both univariate and multivariate analysis. RESULTS: Across all patients, OS
and PFS at 5 years was 59% and 54%, respectively. Increasing T stage correlated
with a statistically significant decrease in OS (P = 0.004) and PFS (P =
0.005). Both overall (P = 0.003) and PFS (P = 0.002) were highest in lifetime
nonsmokers and lowest in current smokers. Patients who commenced treatment in
2010 or later had a significantly greater overall (P = 0.014) and PFS (P =
0.009) compared to those treated prior. Patients with p16 negative tumors had a
significantly lower overall (P < 0.001) and PFS (P < 0.001) compared to those
with p16 positive tumors. Patients treated with cisplatin had an overall and PFS
of 66.8% and 59.9% respectively at 5 years. Patients with a neutrophil-to
lymphocyte ratio of less than 4 at treatment initiation had a significantly
greater overall (P = 0.015) and PFS (P = 0.017). The trend for OS remained
significant in multivariate analysis (P = 0.05). CONCLUSION: A high neutrophil
to-lymphocyte ratio at treatment initiation is a negative predictive marker for
squamous cell carcinoma of the head and neck treated with definitive
chemoradiotherapy.
PMID- 29345109
TI - Effectiveness of smartphone technologies on glycaemic control in patients with
type 2 diabetes: systematic review with meta-analysis of 17 trials.
AB - Patient education and behavioural interventions for self-management of type 2
diabetes mellitus (T2DM) are effective but place demands on manpower resources.
This systematic review aimed to investigate the effectiveness of smartphone
technologies (STs) for improving glycaemic control among T2DM patients. CENTRAL,
MEDLINE, Embase, CINAHL and ScienceDirect were searched through December 2016.
Randomized controlled trials comparing STs with usual diabetes care among T2DM
patients and reporting change in glycated haemoglobin (HbA1c) level were
included. Seventeen trials (2,225 participants) were included. There was a
significant reduction in HbA1c (pooled weighted mean difference: -0.51%; 95%
confidence interval: -0.71% to -0.30%; p < 0.001), favouring ST intervention. The
pooled weighted mean difference was -0.83% in patients with T2DM <8.5 years and
0.22% in patients with T2DM >=8.5 years, with significant subgroup difference (p
= 0.007). No subgroup differences were found among different follow-up durations,
trial locations, patients' age, healthcare provider contract time, baseline body
mass index and baseline HbA1c. Compared with usual diabetes care, STs improved
glycaemic control among T2DM patients, especially for patients at earlier disease
stages (duration of diagnosis <8.5 years). STs could be a complement or
alternative to labour-intensive patient education and behavioural interventions,
but more studies on up-to-date technologies are needed.
PMID- 29345110
TI - Remarkable similarity in Plasmodium falciparum and Plasmodium vivax
geranylgeranyl diphosphate synthase dynamics and its implication for antimalarial
drug design.
AB - Malaria, mainly caused by Plasmodium falciparum and Plasmodium vivax, has been a
growing cause of morbidity and mortality. P. falciparum is more lethal than is P.
vivax, but there is a vital need for effective drugs against both species.
Geranylgeranyl diphosphate synthase (GGPPS) is an enzyme involved in the
biosynthesis of quinones and in protein prenylation and has been proposed to be a
malaria drug target. However, the structure of P. falciparumGGPPS (PfGGPPS) has
not been determined, due to difficulties in crystallization. Here, we created a
PfGGPPS model using the homologous P.vivaxGGPPS X-ray structure as a template. We
simulated the modeled PfGGPPS as well as PvGGPPS using conventional and Gaussian
accelerated molecular dynamics in both apo- and GGPP-bound states. The MD
simulations revealed a striking similarity in the dynamics of both enzymes with
loop 9-10 controlling access to the active site. We also found that GGPP
stabilizes PfGGPPS and PvGGPPS into closed conformations and via similar
mechanisms. Shape-based analysis of the binding sites throughout the simulations
suggests that the two enzymes will be readily targeted by the same inhibitors.
Finally, we produced three MD-validated conformations of PfGGPPS to be used in
future virtual screenings for potential new antimalarial drugs acting on both
PvGGPPS and PfGGPPS.
PMID- 29345111
TI - Association between hepatitis C infection in Thai patients with oral lichen
planus: A case-control study.
AB - AIM: The aim of the present study was to investigate the prevalence of hepatitis
C virus (HCV) infection and evaluate liver enzyme levels in patients from upper
northern Thailand with oral lichen planus (OLP). METHODS: A case-control study of
101 patients with OLP and 101 patients without OLP was conducted. Peripheral
blood was taken from each patient and screened for anti-HCV antibody using
immunochromatography. Positive samples were further confirmed using
chemiluminescent microparticle immunoassay (CMIA) and reverse transcription
polymerase chain reaction. In addition, liver enzyme levels, alanine
transaminase, aspartate transaminase, and alkaline phosphatase were evaluated
using spectrophotometry. RESULTS: Immunochromatography and CMIA revealed that
nine patients with OLP (8.9%) were positive for anti-HCV antibodies, whereas only
one patient without OLP was HCV positive (odds ratio = 9.78). All patients who
were HCV positive had significantly higher liver enzyme levels than patients who
were HCV negative. CONCLUSIONS: The results of the present study indicated that
OLP in certain patients was significantly associated with HCV. This could warrant
screening for HCV-infected patients with OLP in Thailand.
PMID- 29345112
TI - Low NT-proBNP levels in overweight and obese patients do not rule out a diagnosis
of heart failure with preserved ejection fraction.
AB - BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a
heterogeneous syndrome that presents clinicians with a diagnostic challenge. The
use of natriuretic peptides to exclude a diagnosis of HFpEF has been proposed. We
sought to compare HFpEF patients with N-terminal pro-brain natriuretic peptide
(NT-proBNP) level above and below the proposed cut-off. METHODS: Stable patients
(n = 30) with left ventricular (LV) ejection fraction >= 50% were eligible if
they had a diagnosis of HF according to the European Society of Cardiology
diagnostic criteria. Characteristics of patients with NT-proBNP below (<=125
pg/mL) and above (>125 pg/mL) the diagnostic criterion were compared. RESULTS:
There were 19 (66%) women with median age 54 years. Half were African American
(16, 53%), and most were obese. There were no significant differences in clinical
characteristics or medication use between groups. LV end-diastolic volume index
was greater in high NT-proBNP patients (P = 0.03). Left atrial volume index, E/e'
ratio, and E/e' ratio at peak exercise were not significantly different between
NT-proBNP groups. Peak oxygen consumption (VO2 ), VO2 at ventilatory threshold,
and ventilatory efficiency measures were impaired in all patients and were not
significantly different between high and low NT-proBNP patients. CONCLUSIONS: NT
proBNP was below the proposed diagnostic cut-off point of 125 pg/mL in half of
this obese study cohort. Cardiac diastolic dysfunction and cardiorespiratory
fitness were not significantly different between high and low NT-proBNP patients.
These data indicate that excluding the diagnosis of HFpEF based solely on NT
proBNP levels should be discouraged.
PMID- 29345113
TI - Intervention for childhood obesity based on parents only or parents and child
compared with follow-up alone.
AB - OBJECTIVES: The study aims to assess the effects of family-based interventions
targeted to parents only or to parents-and-child for the prevention and treatment
of childhood obesity. METHOD: An open-label randomized study was conducted in 247
children (166 girls, 5-11 years) with body mass index (BMI) in the 85-98th
percentile. Participants were allocated to three groups: parents-only (n = 89),
parents-and-child (n = 84) and follow-up alone (n = 74). The intervention
consisted of 12 once-weekly meetings with a dietician and psychologist. All
children were followed for 2 years. Changes in anthropometric, clinical and
lifestyle outcomes were assessed. RESULTS: The 3-month intervention was completed
by 58 (65.2%) in the parents-only, 61 (72.6%) in the parents-child and 49 (66.2%)
in the control group (P = .554). BMI-standard deviation score (SDS) decreased
from baseline to 3 months in both intervention groups (parents-only: from 1.74 +/
0.31 to 1.66 +/- 0.36, P < .001; parents-child, 1.83 +/- 0.33 to 1.76 +/- 0.36,
P = .012), with no significant change in the controls (1.73 +/- 0.32 to 1.70 +/-
0.31, P = .301). The 2-year follow-up was completed by 45 in each of the
intervention groups (50.5% and 53.5%, respectively) and 37 controls (50%) (P =
.896). Compared with baseline, only the parents-child group showed a significant
decrease in BMI-SDS (1.56 +/- 0.46, P = .006). The rate of children who met the
criteria for metabolic syndrome tended to drop from 6.0% at baseline (14/232) to
1.5% at 3 months (12/137) (P = .109), with no significant between-group
differences in the rate of metabolic syndrome at baseline or at completion of the
intervention. CONCLUSIONS: An intervention programme that focuses on both parents
and children was found to have positive short-term and long-term effects on BMI
SDS.
PMID- 29345114
TI - Introduction to the special issue on myelin plasticity in the central nervous
system.
PMID- 29345115
TI - Metatranscriptome analysis reveals environmental and diel regulation of a
Heterosigma akashiwo (raphidophyceae) bloom.
AB - Despite numerous laboratory studies on physiologies of harmful algal bloom (HAB)
species, physiologies of these algae during a natural bloom are understudied.
Here, we investigated a bloom of the raphidophyte Heterosigma akashiwo in the
East China Sea in 2014 using metabarcode (18S rDNA) and metatranscriptome
sequencing. Based on 18S rDNA analyses, the phytoplankton community shifted from
high diversity in the pre-bloom stage to H. akashiwo predominance during the
bloom. A sharp decrease in ambient dissolved inorganic phosphate and strong up
regulation of phosphate and dissolved organic phosphorus (DOP) uptake genes,
including the rarely documented (ppGpp)ase, in H. akashiwo from pre-bloom to
bloom was indicative of rapid phosphorus uptake and efficient utilization of DOP
that might be a driver of the H. akashiwo bloom. Furthermore, observed up
regulated expression of mixotrophy-related genes suggests potential contribution
of mixotrophy to the bloom. Accelerating photosynthetic carbon fixation was also
implied by the up-regulation of carbonic anhydrase genes during the bloom.
Notably, we also observed a strong morning-to-afternoon shift in the expression
of many genes. Our findings provide insights into metabolic processes likely
important for H. akashiwo bloom formation, and suggest the need to consider
timing of sampling in field studies on this alga.
PMID- 29345116
TI - Notch1 gain of function in skeletal muscles leads to neuromuscular junction
formation defects and neonatal death.
PMID- 29345119
TI - Beyond the headlines - JEADV editor's pick of the year 2017.
PMID- 29345120
TI - Fragrance contact allergy.
PMID- 29345117
TI - Candida auris: A systematic review and meta-analysis of current updates on an
emerging multidrug-resistant pathogen.
AB - From 2009, Candida auris has emerged as a multidrug-resistant ascomycete yeast
pathogen with the capacity for easy transmission between patients and hospitals,
as well as persistence on environmental surfaces. Its association with high
mortalities, breakthrough and persistent candidaemia, inconsistencies in
susceptibility testing results, misidentification by available commercial
identification systems and treatment failure, complicates its management and
detection. Within the last nine years, C. auris has been increasingly reported
from far-Eastern Asia, the Middle East, Africa, Europe, South and North America
with substantial fatalities and misidentification. Herein, I provide a systematic
and thorough review of this emerging pathogen. Meta-analysis showed that at least
742 C. auris isolates have been reported in 16 countries, with most of these
being from India (>=243), USA (>=232) and UK (>=103) (p-value = .0355) within
2013-2017. Most isolates were from males (64.76%) (p-value = .0329) and blood
(67.48%) (p-value < .0001), with substantial crude mortality (29.75%) (p-value =
.0488). Affected patients presented with other comorbidities: diabetes (>=52),
sepsis (>=48), lung diseases (>=39), kidney diseases (>=32) etc. (p-value <
.0001). Resistance to fluconazole (44.29%), amphotericin B (15.46%), voriconazole
(12.67%), caspofungin (3.48%) etc. were common (p-value = .0059). Commonly used
diagnostic tools included PCR (30.38%), Bruker MALDI-TOF MS (14.00%), Vitek 2 YST
ID (11.93%), AFLP (11.55%) and WGS (10.04%) (p-value = .002). Multidrug
resistance, high attributable mortality and persistence are associated with C.
auris infections. Two novel drugs, SCY-078 and VT-1598, are currently in the
pipeline. Contact precautions, strict infection control, periodic surveillance
and cleaning with chlorine-based detergents, efficient, faster and cheaper
detection tools are necessary for prevention, containment and early diagnosis of
C. auris infections.
PMID- 29345122
TI - Ten years of Journal of Biophotonics.
PMID- 29345121
TI - Suspected hypersensitivity to cervicovaginal fluid - what can we learn from the
seminal plasma allergy story?
PMID- 29345123
TI - The effects of lifestyle changes on serum lipid levels in children in a real life
setting.
AB - OBJECTIVE: Studies have shown improvement in lipid levels after institution of
lifestyle changes in children enrolled in closely monitored programs. There
programs are difficult to mimic in real world clinics. We aim to determine if
diet and exercise result in improvement in lipid levels in patients seen in a
designated lipid clinic in a real life setting. DESIGN: Retrospective review of
patients followed for dyslipidemia at the Texas Children's Hospital Lipid Clinic
from May 1, 2012 to May 1, 2015. Patients included were seen more than once, had
repeat lipid testing, and abnormal baseline lipid levels. Multivariate analysis
using mixed models were performed to compare outcomes in patients who did and did
not participate in lifestyle change. RESULTS: Of the 268 patients seen within the
study period, 174 (56% male, 44% female) met inclusion criteria. Median age was
11 years. Compared to patients who did not make lifestyle changes: patients who
made only diet changes demonstrated significant improvement in weight only (slope
= -1.55, P-value = .014), and those who made only exercise changes demonstrated
significant improvements in serum cholesterol (slope = -22.8, P-value = .017) and
non-HDL cholesterol (slope = -28.7, P-value = < .01) levels. Patients who
participated in both diet and exercise demonstrated significant improvement in
weight (slope = -1.13, P-value = .011), diastolic blood pressure (slope = -1.82,
P-value = < .01), and serum lipid levels: LDL (slope = -10.8, P-value = 0.017),
HDL (slope = 1.52, P-value = .24), Triglycerides (slope = -0.11, P-value = .033)
compared to those who did not make lifestyle changes. CONCLUSIONS: Outpatient
management of dyslipidemia is difficult. Only patients who participated in both
diet and exercise showed significant improvement in outcomes when compared to
those who did not make lifestyle changes.
PMID- 29345124
TI - Disposable Morpho menelaus Based Flexible Microfluidic and Electronic Sensor for
the Diagnosis of Neurodegenerative Disease.
AB - Rapid early disease prevention or precise diagnosis is almost impossible in low
resource settings. Natural ordered structures in nature have great potential for
the development of ultrasensitive biosensors. Here, motivated by the unique
structures and extraordinary functionalities of ordered structures in nature, a
biosensor based on butterfly wings is presented. In this study, a flexible Morpho
menelaus (M. menelaus) based wearable sensor is integrated with a microfluidic
system and electronic networks to facilitate the diagnosis of neurodegenerative
disease (ND). In the microfluidic section, the structural characteristics of the
M. menelaus wings up layer are combined with SiO2 nanoparticles to form a
heterostructure. The fluorescent enhancement property of the heterostructure is
used to increase the fluorescent intensity for multiplex detection of two
proteins: IgG and AD7c-NTP. For the electronic section, conductive ink is blade
coated on the under layer of wings for measuring resistance change rate to obtain
the frequency of static tremors of ND patients. The disposable M. menelaus based
flexible microfluidic and electronic sensor enables biochemical-physiological
hybrid monitoring of ND. The sensor is also amenable to a variety of
applications, such as comprehensive personal healthcare and human-machine
interaction.
PMID- 29345125
TI - Naturally acquired bovine besnoitiosis: Disease frequency, risk and outcome in an
endemically infected beef herd.
AB - The recent spread of bovine besnoitiosis warrants further epidemiological
investigations to improve the knowledge on disease development. Thus, a 4-year
longitudinal open cohort study was conducted in the first German cattle herd
naturally infected with Besnoitia besnoiti. At seven herd-visits between 2008 and
2012, fourteen breeding bulls (>1.5 years) and 131 females (>1 year) were
examined clinically and serologically. In females, clinical and serological
prevalences, incidence and remission rates were determined. In addition, the
association of age, antibody levels and number of visible parasitic cysts with
clinical and serological outcome was investigated. The seroprevalence (89.4%
100%) and serological incidence rate (140.5 per 100 animal-years) were
considerably higher than the clinical prevalence (23.5%-36.6%) and clinical
incidence rate (16.7 per 100 animal-years). Of 33 new clinical and 12 new
serological cases, only 6.7% (3/45) attracted attention with clinical signs of
acute bovine besnoitiosis. The apparent serological remission rate (1.9 per 100
animal-years) was considerably lower than the clinical remission rate (37.3 per
100 animal-years). A median cyst score of <1 and mean immunofluorescent antibody
test (IFAT) titre of <=1,600 over the entire observation period was significantly
associated with a negative clinical outcome at the end. Overall cyst score was
not significantly associated with serological outcome and age had no significant
influence on clinical and serological outcome. Within 4 years, there was a
significant reduction in cyst scores and IFAT titres in the same animals, leading
to eight clinically and serologically negative animals in the end. Two initially
negative animals achieved clinical and apparent serological remission in about
2.5 years. In bulls, the time between herd entry and seroconversion was 7-30
months and the serological incidence rate was nearly identical to the rate in
females (142.0 per 100 animal-years). This shows that a high B. besnoiti
prevalence leads to infection of bulls within a short time period.
PMID- 29345126
TI - Enantioselective Synthesis of Boryl Tetrahydroquinolines via Cu-Catalyzed
Hydroboration.
AB - A Cu-catalyzed regio- and enantioselective hydroboration of 1,2-dihydroquinolines
with high yields and excellent enantioselectivities (up to 98% ee) was presented.
This method could be applied in the asymmetric synthesis of the important
intermediates used in the enantioselective synthesis of the potential agent
Sumanirole for the treatment of Parkinson's disease and of the potentially
interesting positive inotropic agent (S)-903.
PMID- 29345127
TI - Monochlorinated to Octachlorinated Polychlorinated Dibenzo-p-dioxin and
Dibenzofuran Emissions in Sintering Fly Ash from Multiple-Field Electrostatic
Precipitators.
AB - Polychlorinated dibenzo-p-dioxin and dibenzofuran (PCDD/F) emissions in fly ash
from multiple-field electrostatic precipitators in different sized sintering
plants were studied. The monochlorinated-trichlorinated and tetrachlorinated
octachlorinated PCDD/F concentrations were higher for small plants (90 m2) than
for medium (91-180 m2) and large (>180 m2) plants. The PCDD/F concentrations and
less-chlorinated PCDD/F contributions to the total PCDD/F concentrations
increased as the fly ash particle size decreased moving through the precipitator
stages; the abundance of monochlorinated-trichlorinated PCDD/F congeners and
homologues also increased. The ash particle size and surface area can be directly
used to indicate monochlorinated-trichlorinated PCDD/Fs and toxic equivalents
(TEQs). Previously ignored PCDD/F emissions in discarded fly ash were identified.
Estimated total monochlorinated-trichlorinated PCDD/F and TEQ emissions in
discarded fly ash were 155 and 1.979 kg TEQ, respectively, in 2003-2014, and the
ratio between annual PCDD/F emissions in discarded fly ash and flue gases has
gradually increased. Reductions in monochlorinated-trichlorinated PCDD/F emitted
in flue gas and fly ash in 2003-2014 were 28 and 40 kg, respectively, because of
the phasing out of small-scale plants. Reductions in TEQs emitted in flue gas and
fly ash in 2003-2014 were 7476 and 180 g TEQ, respectively.
PMID- 29345128
TI - Synthesis of alpha-Formylated N-Heterocycles and Their 1,1-Diacetates from
Inactivated Cyclic Amines Involving an Oxidative Ring Contraction.
AB - A novel synthesis of pyrrolidine-2-carbaldehydes or tetrahydropyridine-2
carbaldehydes from the cascade reactions of N-arylpiperidines or N-arylazepanes
is presented. Mechanistically, the formation of the title compounds involves an
unprecedented oxidative ring contraction of inactivated cyclic amines via
Cu(OAc)2/KI/O2-promoted oxidative cleavage and reformation of the C-N bond.
Interestingly, when PhI(OAc)2 was used in place of KI, 1,1-diacetates of the
corresponding aldehydes were directly obtained with good efficiency. To the best
of our knowledge, this is the first example of regioselective C(sp3)-H bond
functionalization and C(sp3)-N bond activation of saturated cyclic amines using
copper salt and oxygen.
PMID- 29345129
TI - Displacement of Dinitrogen by Oxygen: A Methodology for the Catalytic Conversion
of Diazocarbonyl Compounds to Ketocarbonyl Compounds by 2,6-Dichloropyridine-N
oxide.
AB - Dirhodium(II) catalyzed dinitrogen extrusion from diazocarbonyl compounds by 2,6
dichloropyridine-N-oxide forms ketocarbonyl compounds in near-quantitative
yields. Reactions occur at room temperature, and the pyridine product does not
coordinate with dirhodium(II) to inhibit catalysis. Anhydrous tricarbonyl
compounds, as well as dicarbonyl compounds, are conveniently prepared by this
methodology, and they have been used in situ for catalytic ene and aldol
transformations.
PMID- 29345130
TI - Two Marine Cyanobacterial Aplysiatoxin Polyketides, Neo-debromoaplysiatoxin A and
B, with K+ Channel Inhibition Activity.
AB - The isolation and structure elucidation of two cyanobacterial debromoaplysiatoxin
(DAT) analogues, neo-debromoaplysiatoxin A (1) and neo-debromoaplysiatoxin B (2),
were reported and found to possess 6/10/6 and 6/6/6 fused-ring systems,
respectively, which are rarely seen among aplysiatoxins. Both compounds exhibited
potent blocking activity against Kv1.5 with IC50 values of 6.94 +/- 0.26 and 0.30
+/- 0.05 MUM, respectively. These findings suggest the potential of aplysiatoxin
analogues in modulating ionic channels and also provide links between the DAT
target, protein kinase C, and cell regulation.
PMID- 29345131
TI - Photolithography-Based Nanopatterning Using Re-entrant Photoresist Profile.
AB - Photolithography based on optical mask is widely used in academic research
laboratories due to its low cost, simple mechanism, and ability to pattern in
micron-sized features on a wafer-scale area. Because the resolution is bound by
diffraction limits of the light source, nanoscale patterning using
photolithography requires short-wavelength light source combined with
sophisticated optical elements, adding complexity and cost. In this paper, a
novel method of subwavelength patterning process using conventional i-line
mercury lamp is introduced, without the use of such advanced optical tools. The
method utilizes the re-entrant geometry of image reversal photoresist produced
from the developing process, where a secondary mask is generated by isotropically
depositing a metal layer to cover the re-entrant profile of the photoresist.
Removing the photoresist by applying ultrasonic vibrations in acetone bath
uniformly cracks the metal layer at the sidewalls of the re-entrant profile,
exposing the substrate with a reduced feature size. The width of the initial mask
pattern can be reduced by 400 nm in a controlled manner, regardless of the
original width choice. As a result, the method is shown to achieve sub-100 nm
scale linear patterns compatible for both subsequent deposition process and dry
etching process. Our approach is applicable to various shapes of the patterns and
can be used in electronic device fabrication requiring nanoscale lithography
patterning, such as the gate fabrication of AlGaN/GaN high-electron-mobility
transistor.
PMID- 29345132
TI - Rh(III)-Catalyzed Acceptorless Dehydrogenative Coupling of (Hetero)arenes with 2
Carboxyl Allylic Alcohols.
AB - Rhodium(III)-catalyzed C-H activation of (hetero)arenes and redox-neutral
coupling with 2-carboxyl allylic alcohols has been realized for the construction
of beta-aryl ketones. This reaction occurred efficiently at a relatively low
catalyst loading via initial dehydrogenative alkylation to give a beta-keto
carboxylic acid, followed by decarboxylation.
PMID- 29345133
TI - Stable Organic Radicals as Hole Injection Dopants for Efficient Optoelectronics.
AB - Precursors of reactive organic radicals have been widely used as n-dopants in
electron-transporting materials to improve electron conductivity and enhance
electron injection. However, the utilization of organic radicals in hole
counterparts has been ignored. In this work, stable organic radicals have been
proved for the first time to be efficient dopants to enhance hole injection. From
the absorbance spectra and the ultraviolet photoelectron spectra, we could
observe an efficient electron transfer between the organic radical, (4-N
carbazolyl-2,6-dichlorophenyl)bis(2,4,6-trichlorophenyl)methyl (TTM-1Cz), and the
widely used hole injection material, 1,4,5,8,9,11-hexaazatriphenylene
hexacarbonitrile (HAT-CN). When the unpaired electron of TTM-1Cz is transferred
to HAT-CN, it would be oxidized to a TTM-1Cz cation with a newly formed lowest
unoccupied molecular orbital which is quite close to the highest occupied
molecular orbital (HOMO) of the hole-transporting material (HTM). In this way,
the TTM-1Cz cation would promote the electron extraction from the HOMO of the HTM
and improve hole injection. Using TTM-1Cz-doped HAT-CN as the hole injection
layer, efficient organic light-emitting diodes with extremely low voltages can be
attained.
PMID- 29345134
TI - Nanoscale Imaging of Primary Cilia with Scanning Ion Conductance Microscopy.
AB - Primary cilia are hair-like sensory organelles whose dimensions and location vary
with cell type and culture condition. Herein, we employed scanning ion
conductance microscopy (SICM) to visualize the topography of primary cilia from
different cell types. By combining SICM with fluorescence imaging, we
successfully distinguished between surface cilia that project outward from the
cell surface and subsurface cilia that are trapped below it. The nanoscale
structure of the ciliary pocket, which cannot be easily identified using a
confocal fluorescence microscope, was observed in SICM images. Furthermore, we
developed a topographic reconstruction method using current-distance profiles to
evaluate the relationship between set point and topographic image and found that
a low set point is important for detecting the true topography of a primary
cilium using hopping mode SICM.
PMID- 29345135
TI - The Deposition and Elimination of Glucosinolate Metabolites Derived from Rapeseed
Meal in Eggs of Laying Hens.
AB - This study was to investigate the deposition and elimination of glucosinolate
metabolites including 5-vinyl-1,3-oxazolidine-2-thione (5-VOT) and thiocyanate
ion (SCN-) derived from rapeseed meal (RSM) in hen eggs. During 12 weeks
accumulation phase, the serum triiodothyronine, thyronine, blood urea nitrogen,
kidney index, and thyroid index linearly increased with the RSM at week 12 (P <
0.05). The thyroid histopathology revealed a sign of hyperplastic goiter in hens
fed with 17.64-29.40% RSM. The 5-VOT content of eggs (Y, ng/g) was correlated
with 5-VOT intake (X2, MUg/d.bird) and 5-VOT feeding time (X1, week): Y = 54.94X1
+ 0.51X2 - 430.34 (P < 0.01, R2 = 0.80). The SCN- content of eggs (Y, mg/kg) was
correlated with RSM intake (X2, MUg/d.bird) and RSM feeding time (X1, week): Y =
0.095X1 + 0.302X2 - 0.4211 (P < 0.01, R2 = 0.70). After a 4-week withdrawal of
RSM, the 5-VOT and SCN- did not show in eggs. Taken together, 5.88% RSM with
dietary supplements of 23.55 mg/kg 5-VOT and 10.76 mg/kg SCN- had no effects on
hens with regard to serum parameters, organ index, and thyroid histopathology,
and more than 4 weeks withdrawal should be considered for human and hen health.
PMID- 29345136
TI - Regioselective Reaction of Heterocyclic N-Oxides, an Acyl Chloride, and Cyclic
Thioethers.
AB - Treatment of electron deficient pyridine N-oxides with 4-nitrobenzoyl chloride
and a cyclic thioether in the presence of triethylamine leads to the
corresponding 2-functionalized product in up to a 74% isolated yield. The
transformation can also be accomplished with alternative nitrogen containing
heterocycles, including quinolines, pyrimidines, and pyrazines. To expand the
scope of the transformation, diisopropyl ether can be used as the reaction medium
to allow for the use of solid thioether substrates.
PMID- 29345137
TI - Formal Insertion of Thioketenes into Donor-Acceptor Cyclopropanes by Lewis Acid
Catalysis.
AB - Donor-acceptor cyclopropanes were reacted under Lewis acid catalysis with 3
thioxocyclobutanones as surrogates for disubstituted thioketenes. A broad scope
of 2-substituted tetrahydrothiophenes with a semicyclic double bond was obtained
under mild conditions with high functional group tolerance and in excellent
yield. A sequence of a formal [3 + 2]-cycloaddition followed by the subsequent
release of disubstituted ketene is postulated as the mechanism.
PMID- 29345138
TI - A Four-Step Synthesis of (+/-)-gamma-Lycorane via Pd0-Catalyzed Double C(sp2)
H/C(sp3)-H Arylation.
AB - An expedient synthesis of lycorine alkaloids is reported using a palladium(0)
catalyzed double C-X/C-H arylation as the key step. The selectivity of this
reaction was controlled through the judicious choice of the two halogen atoms,
and its generality was demonstrated through the construction of various
substituted pyrrolophenanthridinones. A selective arene hydrogenation allowed for
the completion of the synthesis of (+/-)-gamma-lycorane in just four steps from
commercially available precursors.
PMID- 29345139
TI - Catalytically Enantioselective Synthesis of Acyclic alpha-Tertiary Amines through
Desymmetrization of 2-Substituted 2-Nitro-1,3-diols.
AB - Highly enantioselective synthesis of acyclic alpha-tertiary amines through
asymmetric desymmetrization is reported. This approach is based on chiral
phosphoric acid mediated, enantioselective, oxidative desymmetrization of 2
substituted 2-nitro-1,3-diolbenzylidine acetals in the presence of DMDO as an
oxidant. The method allows for the formation of a wide variety of chiral 2-nitro
1,3-diols in high enantioselectivity, which could be transformed into optically
pure, unnatural alpha-alkyl series. The synthetic utility of this method has been
further demonstrated by the expedient construction of the core structure of
natural products manzacidins enantioselectively.
PMID- 29345140
TI - High-Efficiency and Stable Organic Solar Cells Enabled by Dual Cathode Buffer
Layers.
AB - Various cathode interface materials have been used in organic solar cells (OSCs)
to realize high performance. However, most cathode interface materials have their
respective weaknesses in maximizing the efficiency or stability of OSCs. Herein,
three kinds of alcohol-soluble cathode interfacial materials are combined with
bathocuproine (BCP) to serve as multifunctional bilayer cathode buffers for the
regular OSCs, and thus greatly enhanced power conversion efficiencies over 10.11%
and significantly improved device stability have been achieved. By utilizing
double interlayers, both light absorption and light distribution in active layer
are improved. Furthermore, double interlayers offer favorable energy-level
alignment, alcohol treatment, and duplicate protection of active layer, resulting
in significantly reduced leakage current, suppressed recombination, and efficient
charge collection. The improved device stability is related to the blocking
effect of the complex formed between BCP and the metal electrode and the
additional protection effect of the underlying alcohol-soluble materials. In view
of the universal use of alcohol-soluble organic electrolyte as cathode buffer
layers and by courtesy of the superiority of the double cathode layers relative
to the monolayer controls, the double interlayer strategy demonstrated here opens
a new way to fully exploiting the potential of OSCs and is believed to be
extended to a wider application.
PMID- 29345142
TI - Mediating Role of Career Coaching on Job-Search Behavior of Older Generations.
AB - This study focuses on career development processes and options for older workers
in South Korea and explores how career coaching enhances their career development
efforts and transition needs. The purpose of this study is to investigate the
structural relationship between older employees' goal-setting, self-efficacy, and
job-search behavior mediated by career coaching. A total of 249 participants were
recruited in a metropolitan city in South Korea. Based on the literature review,
hypotheses were developed and tested on the structural model and the following
findings were revealed. First, the findings indicate a positive effect of self
efficacy on older workers' job-search behavior. Second, the value of career
coaching was found to affect older workers' job-search behavior in the South
Korean context. Third, career-goal commitment alone did not have a positive
significant effect on job-search behavior, but it was influential through the
mediating process of the perceived quality of the career coaching program
provided by an employment center in South Korea.
PMID- 29345141
TI - Creating Hierarchical Pores by Controlled Linker Thermolysis in Multivariate
Metal-Organic Frameworks.
AB - Sufficient pore size, appropriate stability, and hierarchical porosity are three
prerequisites for open frameworks designed for drug delivery, enzyme
immobilization, and catalysis involving large molecules. Herein, we report a
powerful and general strategy, linker thermolysis, to construct ultrastable
hierarchically porous metal-organic frameworks (HP-MOFs) with tunable pore size
distribution. Linker instability, usually an undesirable trait of MOFs, was
exploited to create mesopores by generating crystal defects throughout a
microporous MOF crystal via thermolysis. The crystallinity and stability of HP
MOFs remain after thermolabile linkers are selectively removed from multivariate
metal-organic frameworks (MTV-MOFs) through a decarboxylation process. A domain
based linker spatial distribution was found to be critical for creating
hierarchical pores inside MTV-MOFs. Furthermore, linker thermolysis promotes the
formation of ultrasmall metal oxide nanoparticles immobilized in an open
framework that exhibits high catalytic activity for Lewis acid-catalyzed
reactions. Most importantly, this work provides fresh insights into the
connection between linker apportionment and vacancy distribution, which may shed
light on probing the disordered linker apportionment in multivariate systems, a
long-standing challenge in the study of MTV-MOFs.
PMID- 29345143
TI - Readability of Online Health Information: A Meta-Narrative Systematic Review.
AB - Online health information should meet the reading level for the general public
(set at sixth-grade level). Readability is a key requirement for information to
be helpful and improve quality of care. The authors conducted a systematic review
to evaluate the readability of online health information in the United States and
Canada. Out of 3743 references, the authors included 157 cross-sectional studies
evaluating 7891 websites using 13 readability scales. The mean readability grade
level across websites ranged from grade 10 to 15 based on the different scales.
Stratification by specialty, health condition, and type of organization producing
information revealed the same findings. In conclusion, online health information
in the United States and Canada has a readability level that is inappropriate for
general public use. Poor readability can lead to misinformation and may have a
detrimental effect on health. Efforts are needed to improve readability and the
content of online health information.
PMID- 29345144
TI - Pilot Randomized Controlled Trial of the GO Game Intervention on Cognitive
Function.
AB - This study investigated the effects of an intervention using the game "GO" on
cognitive function in nursing home residents and evaluated the acquisition of GO
according to each stage of dementia. Participants were randomly assigned to
either the GO intervention group or a control group, and the intervention was
performed once weekly for 15 weeks. Cognitive tests were conducted before and
after intervention, and 17 participants were included in the final analysis.
Analysis of covariance demonstrated that in the intervention group, the digit
span total score significantly improved and the digit span backward score was
maintained, whereas these scores decreased in the control group. All
participants, including those who had moderate dementia, acquired the rules of
the game, and participants with mild cognitive impairment and mild dementia could
play the game successfully. This study indicates that GO might improve the
cognitive function of residents living in nursing homes.
PMID- 29345145
TI - Process improvement methodologies uncover unexpected gaps in stroke care.
AB - Background The diagnosis and treatment of acute stroke requires timed and
coordinated effort across multiple clinical teams. Purpose To analyze the
frequency and temporal distribution of emergent stroke evaluations (ESEs) to
identify potential contributory workflow factors that may delay the initiation
and subsequent evaluation of emergency department stroke patients. Material and
Methods A total of 719 sentinel ESEs with concurrent neuroimaging were identified
over a 22-month retrospective time period. Frequency data were tabulated and odds
ratios calculated. Results Of all ESEs, 5% occur between 01:00 and 07:00. ESEs
were most frequent during the late morning and early afternoon hours (10:00
14:00). Unexpectedly, there was a statistically significant decline in the
frequency of ESEs that occur at the 14:00 time point. Conclusion Temporal
analysis of ESEs in the emergency department allowed us to identify an unexpected
decrease in ESEs and through process improvement methodologies (Lean and Six
Sigma) and identify potential workflow elements contributing to this observation.
PMID- 29345146
TI - Quantitative contrast-enhanced ultrasound for monitoring vedolizumab therapy in
inflammatory bowel disease patients: a pilot study.
AB - Background Microvascularization of the bowel wall can be visualized and
quantified non-invasively by software-assisted analysis of derived time-intensity
curves. Purpose To perform software-based quantification of bowel wall perfusion
using quantitative contrast-enhanced ultrasound (CEUS) according to clinical
response in patients with inflammatory bowel disease treated with vedolizumab.
Material and Methods In a prospective study, in 18 out of 34 patients, high
frequency ultrasound of bowel wall thickness using color Doppler flow combined
with CEUS was performed at baseline and after 14 weeks of treatment with
vedolizumab. Clinical activity scores at week 14 were used to differentiate
between responders and non-responders. CEUS parameters were calculated by
software analysis of the video loops. Results Nine of 18 patients (11 with
Crohn's disease and seven with ulcerative colitis) showed response to treatment
with vedolizumab. Overall, the responder group showed a significant decrease in
the semi-quantitative color Doppler vascularization score. Amplitude-derived CEUS
parameters of mural microvascularization such as peak enhancement or wash-in rate
decreased in responders, in contrast with non-responders. Time-derived parameters
remained stable or increased during treatment in all patients. Conclusion
Analysis of bowel microvascularization by CEUS shows statistically significant
changes in the wash-in-rate related to response of vedolizumab therapy.
PMID- 29345148
TI - ERRATUM.
PMID- 29345147
TI - The Complexities of Family Caregiving at Work: A Mixed-Methods Study.
AB - The current project examined the impact of caregiving and caregiving-work
conflict on employees' well-being. A sequential explanatory mixed-methods design
(QUAN->qual) was utilized, and a total of 880 employees from a large health-care
plan employer completed an online survey. Forty-five caregivers who completed the
survey also participated in one of the five focus groups held 1 to 2 months
later. Employed caregivers were significantly ( p < .05) more likely to indicate
poorer physical and mental health than noncaregivers; among caregivers ( n =
370), caregiving-work conflict emerged as the most significant predictor of well
being and fully mediated the empirical relationship between burden and well
being. The focus group findings complemented the quantitative results; many of
the challenges employed caregivers experience stem from their ability or
inability to effectively balance their employment and caregiving roles. The
results suggest the need to focus on caregiving-work conflict when constructing
new or translating existing evidence-based caregiver interventions.
PMID- 29345149
TI - Medical management of brain metastases and leptomeningeal disease in patients
with breast carcinoma.
AB - Breast cancer is the most common malignancy among women and accounts for the
second highest number of cancer-related deaths. With patients surviving longer
due to advances in systemic control, the incidence of CNS involvement is
increasing; however, the management of CNS metastases has not undergone parallel
advancements. The blood-brain barrier limits the efficacy of most systemic
chemotherapies, and the utilization of surgery and radiation beyond first-line
therapy is limited. We will explore the recent developments in the medical
management of breast cancer brain metastasis. Beyond traditional chemotherapy, we
will also discuss targeted therapies and immunotherapies which may provide a
survival benefit to this population and thus, offer further treatment options and
a path for future research and treatment advances.
PMID- 29345150
TI - An Initial Assessment of the Utility of Validated Alcohol and Drug Screening
Tools in Predicting 30-Day Readmission to Adult General Medicine Wards.
AB - Previous studies have identified drug and alcohol use as risk factors for
readmission using claims data, but not by using substance use screening scores.
This preliminary study tested the hypothesis that prevalence of 30-day
readmission would be higher among patients screening positive on the 10-item
Alcohol Use Disorders Identification Test (AUDIT-10) or the 10-item Drug Abuse
Screening Test (DAST-10) tools at intake than among the general patient
population. Social workers screened 4708 adult inpatients using prescreening
questions followed by the AUDIT-10 and/or DAST-10. Patients with positive screens
were followed for readmissions within 30 days of discharge. A positive screening
score on the AUDIT-10 or DAST-10 instrument at intake was associated with higher
risk of readmission to the general medicine wards within 30 days; this
relationship appears complex and subject to mediation. Post hoc chart review
found that the majority of readmissions among patients with positive screens were
not immediately attributable to substance use. Further study is needed to verify
these preliminary findings.
PMID- 29345151
TI - Emerging technologies for biotherapeutic bioanalysis from a high-throughput and
multiplexing perspective: insights from an AAPS emerging technology action
program committee.
AB - This manuscript aims to provide insights and updates on emerging technologies
from a throughput and multiplexing perspective and to update readers on changes
in previously reported technologies. The technologies discussed range from
nascent (ultrasensitive Cira, Intellicyt(r), Dynaxi and CaptsureTM) to the more
established (Ella and SQIDliteTM). For the nascent technologies, there was an
emphasis on user interviews and reviews, where available, to help provide an
unbiased view to our readers. For the Ella, a review of published user data as
well as author and other user experiences are summarized. Due to their emergent
nature, all the technologies described are applicable in the early drug
development stage, may require an upfront investment of capital and may not
perform as expected.
PMID- 29345152
TI - Changes in radiotherapy fractionation-breast cancer.
AB - Conventional fractionation for half a century has been justified on the basis
that 2.0 Gy fractions spare dose-limiting late-responding normal tissues to a
greater degree than cancerous tissues. Early indications that breast cancer
responds more strongly to fraction size than many other common cancers were
followed several decades of investigation, but there is now reliable Level I
evidence that this is the case. Four randomised trials testing fraction sizes in
the range 2.7-3.3 Gy have reported 10-year follow up in almost 8000 patients, and
they provide robust estimates of alpha/beta in the range of 3 Gy. The implication
is that there are no advantages in terms of safety or effectiveness of persisting
with 2.0 Gy fractions in patients with breast cancer. 15- or 16-fraction
schedules are replacing the conventional 25-fraction regimen as a standard of
care for adjuvant therapy in an increasing number of countries. A number of
concerns relating to the appropriateness of hypofractionation in patient
subgroups, including those treated post-mastectomy, advanced local-regional
disease and/or to lymphatic pathways are addressed. Meanwhile, hypofractionation
can be exploited to modulate dose intensity across the breast according to
relapse risk by varying fraction size across the treatment volume. The lower
limits of hypofractionation are currently being explored, one approach testing a
5-fraction schedule of local-regional radiotherapy delivered in 1 week.
PMID- 29345153
TI - Selective serotonin reuptake inhibitor use in pregnant women; pharmacogenetics,
drug-drug interactions and adverse effects.
AB - INTRODUCTION: Possible negative effects of selective serotonin reuptake
inhibitors (SSRIs) in pregnancy relate to congenital anomalies, negative
perinatal events and neurodevelopmental outcome. Many studies are confounded by
the underlying maternal disease and by pharmacogenetic and pharmacokinetic
differences of these drugs. Areas covered: The possible interactions of SSRIs and
serotonin and norepinephrine reuptake inhibitors with other drugs and the known
effects of SSRIs on congenital anomalies, perinatal and neurodevelopmental
outcome. Expert opinion: SSRIs should be given with caution when combined with
other drugs that are metabolized by cytochrome P450 enzymes. SSRIs apparently
increase the rate of severe cardiac malformations, induce neonatal adaptation
problems in up to 30% of the offspring, increase the rate of persistent pulmonary
hypertension of the newborn and possibly slightly increase the rate of
prematurity and low birth weight. Most neurodevelopmental follow up studies did
not find significant cognitive impairments except some transient gross motor
delay, slight impairment of language abilities and possibly behavioral changes.
The literature on the possible association of SSRIs with autism spectrum disorder
is inconsistent; if an association exists, it is apparently throughout pregnancy.
The risk associated with treatment discontinuation seems to outweigh the risk of
treatment, as severe maternal depression may negatively affect the child's
development. If needed, treatment should continue in pregnancy with the minimal
effective dose.
PMID- 29345154
TI - Trends and repetition of non-fatal suicidal behaviour: analyses of the Gold Coast
University Hospital's Emergency Department.
AB - : Objective The aim of the current paper is to analyse time trends of non-fatal
suicidal behaviour (NFSB) and its repetition at the Gold Coast in 2005-2015.
Methods Data on presentations for NFSB were obtained from the Emergency
Department (ED) Information System. Potential cases were identified through
keyword searches, which were further scrutinised and coded. Annual person-based
age-standardised rates for NFSB were calculated. Chi-square test, Poisson
regression and Cox proportional hazards regression were used. RESULTS: There was
a significant increase in the age-standardised rates of NFSB for males (incidence
Rate Ratio = 1.05; 95% confidence interval (CI): 1.04-1.07) and females (iRR =
1.06; 95% CI: 1.04-1.07). Age-specific rates showed significant increases for all
age groups, except 25-34 and 55+ for females. Different types of poisoning were
the predominant method of NFSB (poisoning only - 61.7% of episodes), followed by
cutting (23%). Within the first year after the index episode, 13.4% of subjects
repeated NFSB. Multivariate Cox regression model showed that sex, age and method
predicted repetition. CONCLUSION: The increasing trends of NFSB and relatively
high repetition rates emphasise the need for preventative actions. Monitoring of
NFSB at the ED level should be further extended in Australia.
PMID- 29345155
TI - Minimally invasive adrenal surgery: virtue or vice?
AB - Adrenocortical carcinoma (ACC) is a rare malignancy associated with poor
prognosis despite available treatments. In patients with localized or locally
advanced disease, complete resection with negative margins offers the only
potential for cure. Unfortunately, most patients develop local and distant
recurrence following initial resection highlighting the importance of meticulous
surgical technique in the hands of an experienced surgeon. While minimally
invasive surgery (MIS) has supplanted open surgery for small to medium-sized
benign adrenal tumors, controversy surrounds the use of MIS for resection of ACC.
We sought to provide an overview of the key oncological principles in the
surgical management of ACC and to critically review the literature comparing
outcomes between the open and MIS approaches.
PMID- 29345156
TI - Pharmacokinetic drug evaluation of opicapone for the treatment of Parkinson's
disease.
AB - INTRODUCTION: Opicapone (OPC) is a novel, potent, reversible, and purely
peripheral third-generation COMT inhibitor, which provides an enhancement in
levodopa (L-Dopa) availability. It represents adjunctive therapy for L-Dopa
treated patients with PD and motor fluctuations. Areas covered: The purpose of
this study was to evaluate pharmacokinetic of OPC for the treatment of PD. Expert
commentary: Oral OPC exhibits linear, dose-dependent absorption. However,
following concomitant ingestion of a high-fat, high-calorie meal, the maximum
plasma concentration will be decreased. A once-daily bedtime administration of
OPC 1 h after the last daily L-Dopa/AADCi, are considered to avoid any
interaction during the L-Dopa absorption phase. There are no clinically relevant
effects of age (in adults), renal impairment or race on the pharmacokinetics of
OPC. OPC dose adjustment is not needed in patients with mild to moderate chronic
hepatic impairment. Opicapone exhibits the lowest potential for cytotoxicity in
comparison with other COMT inhibitors. It significantly decreases COMT activity,
with half-life of COMT inhibition in human erythrocytes of 61.6 h and increases
systemic exposure to L-Dopa. This provides an enhancement in L-Dopa availability
that translates into clinical benefit for PD patients in terms of significant
decrease of OFF periods and increase in ON-time without troublesome dyskinesia.
PMID- 29345157
TI - Evaluation of serum cysteine-rich protein 61 levels in patients with coronary
artery disease.
AB - AIM: The aim is to evaluate serum cysteine-rich protein 61 (Cyr61) levels in
patients with coronary artery disease (CAD). PATIENTS & METHODS: Serum Cyr61
levels were measured in 180 patients with CAD and 74 participants without CAD.
RESULTS: Serum Cyr61 levels were significantly higher in CAD patients. Patients
with acute coronary syndrome showed significantly higher Cyr61 than those with
stable angina pectoris. Serum Cyr61 levels in complex lesion group were
significantly higher. Serum Cyr61 was positively correlated with Gensini score
and C-reactive protein. Multivariable logistic regression analyses demonstrated
that serum Cyr61 levels were independently correlated with the existence of CAD
(p = 0.01). CONCLUSION: Our study suggested Cyr61 as a potential biomarker in
characterizing CAD and therapeutic target for CAD.
PMID- 29345158
TI - The impact of probiotics and n-3 long-chain polyunsaturated fatty acids on
intestinal permeability in pregnancy: a randomised clinical trial.
AB - A disruption in intestinal barrier integrity may predispose individuals to
metabolic aberrations, particularly during the vulnerable period of pregnancy. We
investigated whether intestinal permeability, as measured by serum zonulin
concentration, changes over the duration of pregnancy and whether this change is
reflected in lipopolysaccharide (LPS) activity. Second, we tested in a randomised
double-blind placebo controlled clinical trial the impact of consuming dietary
probiotics and/or long chain polyunsaturated fatty acid (LC-PUFA) supplements in
lowering serum zonulin concentration and LPS activity. The probiotic supplement
was a combination of two bacteria, Bifidobacterium animalis ssp. lactis 420 and
Lactobacillus rhamnosus HN001. This study included 200 overweight pregnant women
participating in an on-going study; participants were randomised to consume
either (1) probiotics, (2) LC-PUFA, (3) probiotics and LC-PUFA, or (4) placebo
for each supplement. Blood samples were obtained at early, the baseline, and late
pregnancy (mean 14 and 35 weeks of gestation, respectively). Serum zonulin
concentration increased from early (mean (standard deviation): 62.7 (12.9) ng/ml)
to late pregnancy by 5.3 (95%CI 3.7-6.9) ng/ml, and LPS activity increased from
(0.16 (0.04) EU/ml) by 0.04 (95%CI 0.03-0.05) EU/ml. No differences among the
intervention groups were detected in the change from early to late pregnancy in
serum zonulin concentration (P=0.8) or LPS activity (P=0.2). The change in serum
zonulin concentration during the pregnancy was associated with the weeks of
follow up (r=0.25, P<0.001). Serum LPS activity was correlated with higher
maternal weight gain (r=0.19, P=0.008). As a conclusion, intestinal permeability
increased with the progression of pregnancy in overweight and obese women and was
reflected in LPS activity. No efficacy of supplementation with probiotics and/or
LC-PUFA was demonstrated in pregnancy-induced changes in serum zonulin
concentration or LPS activity.
PMID- 29345159
TI - Weighing in on the risks and benefits of probiotic use in HIV-infected and
immunocompromised populations.
AB - Probiotics are used in the prophylaxis and treatment of several conditions,
including irritable bowel syndrome, diarrhoea, necrotising enterocolitis (NEC)
and colic in infants. Despite the long history of probiotic use in humans, there
is still significant debate about their efficacy and safety, particularly in HIV
infected and immunocompromised individuals. Here, we reviewed the safety and
adverse event (AE) reporting from clinical trials that have tested probiotics in
at risk populations, including HIV-infected individuals, the terminally ill and
elderly, and neonates. Our analysis suggests that the benefits of probiotic
therapy outweigh their potential risks in HIV-infected populations, and in the
treatment of colic and NEC in low birth weight or premature neonates. Most case
reports of severe AEs were in the elderly and terminally ill, or in those with
additional severe medical conditions. We conclude that probiotic use, as
adjunctive treatment, is effective and safe in the majority of patients including
HIV-infected individuals, although special care should be taken in individuals
with extreme immunosuppression and severe medical conditions in all ages.
PMID- 29345160
TI - Inherited forms of bladder cancer: a review of Lynch syndrome and other inherited
conditions.
AB - Environmental factors that play a role in the urothelial carcinogenesis have been
well characterized. Current research is continuously exploring potential
heritable forms of bladder cancer. Lynch syndrome is a well-known inheritable
disease that increases the risk for a variety of cancers, including urothelial
carcinomas. Screening of patients with known Lynch syndrome is important to
evaluate for development of new primary tumors. Further study may provide more
information on what level of follow-up each patient needs. Recent data suggest
that mismatch repair mutations confer a greater risk for urothelial cancer.
Additional large patient series as well as advancement of molecular testing may
provide triage for Lynch syndrome patients in regards to the frequency and type
of screening best suited for individual patient.
PMID- 29345161
TI - Caffeine Improves Triathlon Performance: A Field Study in Males and Females.
AB - The ergogenic effect of caffeine on endurance exercise is commonly accepted. We
aimed to elucidate realistically the effect of caffeine on triathlon event
performance using a field study design, while allowing investigation into
potential mechanisms at play. A double-blind, randomized, crossover field trial
was conducted. Twenty-six triathletes (14 males and 12 females; mean +/- SD: age
= 37.8 +/- 10.6 years, habitual caffeine intake = 413 +/- 505 mg/day, percentage
body fat = 14.5 +/- 7.2%, and training/week = 12.8 +/- 4.5 hr) participated in
this study. Microencapsulated caffeine (6 mg/kg body weight) was supplemented 60
min pretrial. Performance data included time to completion, rating of perceived
exertion, and profile of mood states. Blood samples taken before, during, and
postrace were analyzed for cortisol, testosterone, and full blood count.
Capillary blood lactate concentrations were assessed prerace, during transitions,
and 3, 6, 9, 12, and 15 min after triathlons. Caffeine supplementation resulted
in a 3.7% reduction in swim time (33.5 +/- 7.0 vs. 34.8 +/- 8.1 min, p < .05) and
a 1.3% reduction in time to completion (149.6 +/- 19.8 vs. 151.5 +/- 18.6 min, p
< .05) for the whole group. Gender differences and individual responses are also
presented. Caffeine did not alter the rating of perceived exertion significantly,
but better performance after caffeine supplementation suggests a central effect
resulting in greater overall exercise intensity at the same rating of perceived
exertion. Caffeine supplementation was associated with higher postexercise
cortisol levels (665 +/- 200 vs. 543 +/- 169 nmol/L, p < .0001) and facilitated
greater peak blood lactate accumulation (analysis of variance main effect, p <
.05). We recommend that triathlon athletes with relatively low habitual caffeine
intake may ingest 6 mg/kg body weight caffeine, 45-60 min before the start of
Olympic-distance triathlon to improve their performance.
PMID- 29345162
TI - Genetic defect of a combined 17 alpha-hydroxylase/17,20-lyase deficiency patient
with adrenal crisis.
AB - Combined 17 alpha-hydroxylase/17,20-lyase deficiency (17OHD) is a rare autosomal
recessive disease that is a type of congenital adrenal hyperplasia, which results
in hypertension, hypokalemia, sexual infantilism, primary amenorrhea in females
(46,XX), or pseudohermaphroditism in males (46,XY). It is mainly caused by
mutation in the CYP17A1 gene, which encodes a key enzyme in the steroidogenic
pathway. However, these patients rarely experience adrenal crisis, due to
abnormally high corticosterone levels. Here, we report a 17OHD patient who
experienced clinical adrenal crisis on day 1 after gonadectomy. Her (46,XY)
genetic defect was c0.715 C > T p.Arg239-stop in exon 4 of CYP17A1, which was
confirmed by targeted sequence capture/high-throughput sequencing and Sanger
sequencing technology. To the best of our knowledge, 17OHD with adrenal crisis
has not been reported previously, and the reason why it arose in this patient
might have been inappropriate glucocorticoid administration during the
perioperative period.
PMID- 29345163
TI - Low dose HP-hMG in an antagonist protocol for IVF in ovulatory and anovulatory
patients with high AMH.
AB - Women with high-AMH levels have an increased risk of ovarian hyperstimulation
syndrome (OHSS). Studies have suggested that highly purified menotropin (HP-hMG)
Menopur(r) reduces the risk. We, therefore, studied use of low-dose (112.5
IU/day) HP-hMG in ovulatory and anovulatory patients with high AMH (>32 pmol/L).
The primary endpoint was the distribution of patients with appropriate,
excessive, and inadequate response (5-14, >=15, and <=4 oocytes). Another
endpoint was frequency of OHSS. Totally 115 women were included and 78 (67.8%)
had an appropriate, 8 (7.0%) an excessive, and 29 (25.2%) an inadequate response.
The number of oocytes was independent on AMH levels and ovulatory status but
declined significantly with increasing bodyweight (R2 = 0.07, p < .01). The
ongoing pregnancy rate per started cycle was 47.0%. Three (2.6%) developed OHSS,
two had cancelation of the cycle and seven patients had GnRH agonist triggering
to prevent OHSS. Selective use of a low dose of HP-hMG in patients with high
levels of AMH provides 5-14 oocytes in more than two-thirds of the patients and
is safe with low risk of OHSS. The number of aspirated oocytes was independent of
AMH levels and ovulatory status, but inversely related to body weight.
PMID- 29345164
TI - A positive association between interleukin-1 receptor antagonist and insulin
resistance in postmenopausal women.
AB - OBJECTIVE: The purpose of this study was to determine whether higher circulating
interleukin-1 receptor antagonist (IL-1Ra), an anti-inflammatory cytokine, was
associated with insulin resistance in postmenopausal women. METHODS: We measured
IL-1Ra concentrations in 160 naturally postmenopausal women without a history of
diabetes mellitus. A Pearson coefficient was computed to assess the relationship
between plasma IL-1Ra and homeostasis model assessment of insulin resistance
(HOMA-IR). The association between HOMA-IR and IL-1Ra plasma level above the
median was assessed by logistic regression. Linear regression was used to explore
the determinants of IL-1Ra plasma levels. RESULTS: A significant positive
correlation existed between IL-1Ra and HOMA-IR (r = 0.42, p < .0001). The upper
tertile group of HOMA-IR was associated with approximately 4.5-fold increased
risk of plasma IL-1Ra level above the median compared with the low-tertile group
after adjustments. When multiple correlates were entered into the regression
model simultaneously, only Log HOMA-IR remained significantly related to Log IL
1Ra (p = .007). CONCLUSIONS: Our results demonstrated a positive association
between plasma IL-1Ra and insulin resistance in postmenopausal women. This
analysis suggested that insulin resistance was an important determinant of
circulating IL-1Ra for these women.
PMID- 29345165
TI - Oral contraceptive pills as an option for non-surgical management of retained
products of conception - a preliminary study.
AB - Many Patients with persistent retained products of conception prefers to avoid
surgical interventions, such as a dilatation and curettage (D&C) that might pose
an additional future risk to their already compromised fertility or obstetric
performance. The aim of this study was to the possibility of induced withdrawal
bleeding following oral contraceptive administration as a non-surgical treatment
for patients with persistent retained products of conception (RPOC). A
retrospective study of patients presenting with retained products of conception
(RPOC) after failed expectant management or after treatment with PGE1 was
performed. Twelve women presenting with RPOC at <=8 weeks gestation with minimal
to mild vaginal bleeding and no signs of infection were treated with oral
contraceptive pill (OCP) containing 0.03 mg ethinylestradiol and 0.15 mg of
desogestrel for 3 weeks. Out of the 12 patients treated, nine women (75%)
successfully expelled the RPOC after completing the three-week course of OCPs.
The three cases (25%) that did not resolve following OCP treatment had pregnancy
products with positive blood flow on Doppler examination. We conclude that OCPs
may be a useful medical treatment option for persisting RPOC in selected patients
with absence blood flow on Doppler examination wishing to avoid surgical
intervention.
PMID- 29345166
TI - Effects of Coffee Components on Muscle Glycogen Recovery: A Systematic Review.
AB - Coffee is one of the most consumed beverages in the world, and it can improve
insulin sensitivity, stimulating glucose uptake in skeletal muscle when adequate
carbohydrate intake is observed. The aim of this review is to analyze the effects
of coffee and coffee components on muscle glycogen metabolism. A literature
search was conducted according to Preferred Reporting Items for Systematic
Reviews and Meta-Analysis, and seven studies were included, that explored the
effects of coffee components on various substances and signaling proteins. In one
of the studies with humans, caffeine was shown to increase glucose levels,
Ca2+/calmodulin-dependent protein kinase phosphorylation, glycogen resynthesis
rates, and glycogen accumulation after exercise. After intravenous injection of
caffeine in rats, caffeine increased adenosine monophosphate-activated protein
kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, and glucose
transport. In in vitro studies, caffeine raised AMPK and ACC phosphorylation,
increasing glucose transport activity and reducing energy status in rat muscle
cells. Cafestol and caffeic acid increased insulin secretion in rat beta cells
and glucose uptake into human muscle cells. Caffeic acid also increased AMPK and
ACC phosphorylation, reducing the energy status and increasing glucose uptake in
rat muscle cells. Chlorogenic acid did not show any positive or negative effect.
The findings from this review must be taken with caution due to the limited
number of studies on the subject. In conclusion, various coffee components had a
neutral or positive role in the metabolism of glucose and muscle glycogen,
whereas no detrimental effect was described. Coffee beverages should be tested as
an option for athletes' glycogen recovery.
PMID- 29345167
TI - Dietary Supplements for Health, Adaptation, and Recovery in Athletes.
AB - Some dietary supplements are recommended to athletes based on data that supports
improved exercise performance. Other dietary supplements are not ergogenic per
se, but may improve health, adaptation to exercise, or recovery from injury, and
so could help athletes to train and/or compete more effectively. In this review,
we describe several dietary supplements that may improve health, exercise
adaptation, or recovery. Creatine monohydrate may improve recovery from and
adaptation to intense training, recovery from periods of injury with extreme
inactivity, cognitive processing, and reduce severity of or enhance recovery from
mild traumatic brain injury (mTBI). Omega 3-fatty acid supplementation may also
reduce severity of or enhance recovery from mTBI. Replenishment of vitamin D
insufficiency or deficiency will likely improve some aspects of immune, bone, and
muscle health. Probiotic supplementation can reduce the incidence, duration, and
severity of upper respiratory tract infection, which may indirectly improve
training or competitive performance. Preliminary data show that gelatin and/or
collagen may improve connective tissue health. Some anti-inflammatory
supplements, such as curcumin or tart cherry juice, may reduce inflammation and
possibly delayed onset muscle soreness (DOMS). Beta-hydroxy beta-methylbutyrate
(HMB) does not consistently increase strength and/or lean mass or reduce markers
of muscle damage, but more research on recovery from injury that includes periods
of extreme inactivity is needed. Several dietary supplements, including creatine
monohydrate, omega 3-fatty acids, vitamin D, probiotics, gelatin, and
curcumin/tart cherry juice could help athletes train and/or compete more
effectively.
PMID- 29345168
TI - Mother's age at menopause but not own age at menarche has an impact on ovarian
reserve.
AB - To detect clinical parameters impacting ovarian reserve, data were analyzed from
573 patients who had an anti-Mullerian hormone (AMH) measurement for infertility
treatment. No impact was found on the age at menarche but a significant
diminished ovarian reserve was observed when a patient's mother was menopausal
before age 50. These data suggest that ovarian reserve must be monitored in such
patients to offer them fertility preservation when at risk of premature ovarian
insufficiency (POI).
PMID- 29345169
TI - A case of diffuse large B-cell lymphoma with MYC gene cluster amplification
related to chromothripsis.
PMID- 29345170
TI - Cemented total hip replacement in patients under 55 years.
AB - Background and purpose - About 86,000 total hip replacements (THR) have been
registered in patients under 55 years in the National Joint Registry of England
and Wales (NJR). The use of uncemented implants has increased, despite their
outcomes not having been proven to be significantly better than cemented implants
in this registry. We determined the implant survivorship and functional outcomes
of cemented THR in patients under 55 years at a minimum follow-up of 22 years.
Patients and methods - 104 hips in 100 patients were included in this prospective
study. Functional outcome was assessed using the Harris Hip Score and radiographs
were assessed for implant failure and "at risk" of failure. Kaplan-Meier
survivorship analysis was performed. Results - 89% of hips showed good to
excellent results at final follow-up with a mean Harris Hip Score of 88 at a mean
follow-up of 25 years. Revision was performed in 3/104 hips. 14 acetabular
components and 4 femoral components were "at risk" of failure. The survivorship
at minimum 22 years with revision for any reason as the end-point was 97% (95% CI
95-98). Interpretation - Cemented hip replacements perform well in young patients
with good long-term functional and radiographic outcomes.
PMID- 29345171
TI - Comparison of Bioelectrical Impedance Analysis and Dual-Energy X-Ray
Absorptiometry for Estimating Bone Mineral Content.
AB - The purpose of this study was to validate single-frequency hand-to-foot
bioelectrical impedance analysis (HFBIA) for estimating bone mineral content
(BMC) using dual-energy X-ray absorptiometry as the criterion measure in healthy
men and women aged 18-40 years. A total of 80 men and women participated in this
study. BMC was estimated on the same day using HFBIA and dual-energy X-ray
absorptiometry. The HFBIA device provided higher mean BMC values in men and the
entire sample, but not in women. A smaller standard error of estimate was
observed in women (0.20, corresponding to 8% of the mean reference BMC values)
compared with men (0.39, corresponding to 12% of the mean reference BMC values)
and the combined sample (0.31). HFBIA provided a smaller constant error and
individual estimation error indicated by the 95% limits of agreement in women (
0.05 +/- 0.39) compared with men (-0.16 +/- 0.78) and the entire sample (-0.10 +/
0.63). In conclusion, although BMC values were found to be more accurate in
women, HFBIA overestimated BMC compared with dual-energy X-ray absorptiometry,
especially in individuals with lower values. Given these results, using HFBIA to
measure BMC would be inappropriate for diagnostic purposes.
PMID- 29345172
TI - Real-world data on first relapse of acute lymphoblastic leukemia in patients >55
years.
PMID- 29345173
TI - Effects of Three-Day Serial Sodium Bicarbonate Loading on Performance and
Physiological Parameters During a Simulated Basketball Test in Female University
Players.
AB - The aim of this study was to investigate the effect of 3-day serial sodium
bicarbonate ingestion on repeated sprint and jump performance. Fifteen female
university basketball players (23.3 +/- 3.4 years; 173.1 +/- 5.8 cm; 65.8 +/- 6.3
kg; 23.6 +/- 4.9% body fat) ingested 0.4 g/kg body mass of sodium bicarbonate or
placebo for 3 days (split in three equal daily doses), before completing a
simulated basketball exercise. Sprint and circuit times, jump heights,
performance decrements, and gastrointestinal side effects were recorded during
the test, and blood lactate concentration was measured pre- and posttest. Sodium
bicarbonate supplementation led to significant decreases in mean sprint times
(1.34 +/- 0.23 vs. 1.70 +/- 0.41 s, p = .008, 95% confidence intervals [-0.54,
0.10 s]) and mean circuit times (30.6 +/- 2.0 vs. 31.3 +/- 2.0 s, p = .044) and
significantly greater mean jump height (26.8 [range 25.2-34.2] vs. 26.0 [range
25.6-33.6] cm, p = .013) compared with placebo. Performance decrement was
significantly less for sprints with sodium bicarbonate compared with placebo (9.9
[range 3.4-37.0]% vs. 24.7 [range 4.1-61.3]%, p = .013), but not different for
jumps (13.1 +/- 4.5% vs. 12.5 +/- 3.1%, p = .321) between conditions. No
differences in gastrointestinal side effects were noted between conditions.
Significantly greater postexercise blood lactate concentrations were measured in
the sodium bicarbonate condition compared with the placebo condition (8.2 +/- 2.8
vs. 6.6 +/- 2.4 mmol/L, p = .010). This study is the first to show that serial
loading of sodium bicarbonate is effective for basketball players to improve
repeated sprint and jump performance during competition, or withstand greater
training load during practice sessions without any gastrointestinal side effects.
PMID- 29345174
TI - Using Contemporary Behavior Change Science to Design and Implement an Effective
Nutritional Intervention Within Professional Rugby League.
AB - Designing and implementing successful dietary intervention is integral to the
role of sport nutrition professionals as they attempt to positively change the
dietary behavior of athletes. High-performance sport is a time-pressured
environment where immediate results can often supersede pursuit of the most
effective evidence-based practice. However, efficacious dietary intervention
necessitates comprehensive, systematic, and theoretical behavioral design and
implementation, if the habitual dietary behaviors of athletes are to be
positively changed. Therefore, this case study demonstrates how the Behaviour
Change Wheel was used to design and implement an effective nutritional
intervention within a professional rugby league. The eight-step intervention
targeted athlete consumption of a high-quality dietary intake of 25.1 MJ each day
to achieve an overall body mass increase of 5 kg across a 12-week intervention
period. The capability, opportunity, motivation, and behavior model and
affordability, practicability, effectiveness/cost-effectiveness, acceptability,
safety, and equity criteria were used to identify population-specific
intervention functions, policy categories, behavior change techniques, and modes
of intervention delivery. The resulting intervention was successful, increasing
the average daily energy intake of the athlete to 24.5 MJ, which corresponded in
a 6.2 kg body mass gain. Despite consuming 0.6 MJ less per day than targeted,
secondary outcome measures of diet quality, strength, body composition, and
immune function all substantially improved, supporting sufficient energy intake
and the overall efficacy of a behavioral approach. Ultimately, the Behaviour
Change Wheel provides sport nutrition professionals with an effective and
practical stepwise method to design and implement effective nutritional
interventions for use within high-performance sport.
PMID- 29345175
TI - A role for bone turnover markers beta-CrossLaps (CTX) and amino-terminal
propeptide of type I collagen (PINP) as potential indicators for disease
progression from MGUS to multiple myeloma.
AB - Multiple myeloma (MM) is characterized by bone lesions arising due to unbalanced
bone remodeling. Changes in the bone formation marker amino-terminal propeptide
of type I collagen (PINP) and the bone resorption marker beta-CrossLaps (CTX)
reflect physiologic bone turnover. Whether PINP and CTX have a role in disease
progression from monoclonal gammopathy of undetermined significance (MGUS) to MM
is unknown. In this cross-sectional follow-up study, 241 patients with MM or MGUS
were included. Serum levels of PINP and CTX were significantly higher in MM
patients compared to MGUS. Moreover, increasing concentrations of PINP and CTX
were observed in those MGUS patients progressing to MM, whereas PINP and CTX
levels remained unchanged in MGUS patients with stable disease. In conclusion,
these data indicate a potential role of PINP and CTX as biomarkers for the
progression of MGUS to MM.
PMID- 29345177
TI - Prognostic significance of cathepsin L expression in pediatric acute myeloid
leukemia.
AB - Overexpression of cathepsin L (CTSL), an endolysosomal cysteine protease, is
associated with inferior survival of patients with various human malignancies. We
evaluated the expression/activity of CTSL in peripheral blood mononuclear cells
(PBMCs) and bone marrow mononuclear cells (BMMCs) of 103 pediatric acute myeloid
leukemia (AML) patients to assess its prognostic significance in this malignancy.
Thirty-five healthy siblings of patients served as controls. Our results revealed
significantly higher CTSL activity (p < .0001), protein (p < .05), and mRNA
levels (p < .01) in both PBMCs and BMMCs of patients as compared with controls.
BMMCs displayed higher activity of CTSL than PBMCs (p < .01). A dramatic
reduction in CTSL activity was recorded after chemotherapy in a significant
proportion (74%) of patients (p < .0001). By multivariate analysis, CTSL in BMMCs
emerged as a strong independent prognostic marker for overall survival (OS) (p =
.004). Thus, our results suggest the potential utility of CTSL in predicting the
outcome of pediatric AML.
PMID- 29345176
TI - Bone marrow VEGFC expression is associated with multilineage dysplasia and
several prognostic markers in adult acute myeloid leukemia, but not with
survival.
AB - Vascular endothelial growth factor C (VEGFC) stimulates leukemia cell
proliferation and survival, and promotes angiogenesis. We studied VEGFC
expression in bone marrow samples from 353 adult acute myeloid leukemia (AML)
patients and its relationship with several clinical, cytogenetic, and molecular
variables. We also studied the expression of 84 genes involved in VEGF signaling
in 24 patients. We found that VEGFC expression was higher in AML patients with
myelodysplasia-related changes (AML-MRC) than in patients with non-AML-MRC. We
also found an association between VEGFC expression and the patient cytogenetic
risk group, with those with a worse prognosis having higher VEGFC expression
levels. No correlation was observed between VEGFC expression and survival or
complete remission. VEGFC expression strongly correlated with expression of the
VEGF receptors FLT1, KDR, and NRP1. Thus, in this series, VEGFC expression was
increased in AML-MRC and in subgroups with a poorer prognosis, but has no impact
on survival.
PMID- 29345178
TI - Frequency and Factors Associated With Honorary Authorship in Indian Biomedical
Journals: Analysis of Papers Published From 2012 to 2013.
AB - Honorary authorship is the inclusion of an author on an article whose
contribution does not warrant authorship. We conducted an Internet-based survey
among first authors publishing in Indian biomedical journals from 2012 to 2013 to
study the frequency and factors associated with honorary authorship. The response
rate was 27% (245/908) with the prevalence of perceived, International Committee
of Medical Journal Editors (ICMJE)-defined, and unperceived honorary authorship
of 20.9% (50/239), 60% (147/245), and 46.9% (115/245), respectively. Those
residing in India were found to list more honorary authors. We hope to increase
awareness of the ICMJE authorship guidelines and the general issue of honorary
authorship among researchers in India and elsewhere.
PMID- 29345179
TI - Regulatory Support Improves Subsequent IRB Approval Rates in Studies Initially
Deemed Not Ready for Review: A CTSA Institution's Experience.
AB - We evaluated the impact of a regulatory support service (known as the Regulatory
Knowledge and Support [RKS] program), part of the Medical University of South
Carolina's Clinical and Translational Science Award, on the success of
Institutional Review Board (IRB) applications that have previously been deemed by
the IRB to be Not Ready for Review (NRR). At the time of this evaluation, 77
studies had been deemed NRR, 53 of which came from trainees and junior faculty.
All the applications that received regulatory support either received IRB
approval or were deemed to not be research, and therefore did not require IRB
review. In all, 39.1% (n = 18) of the research teams who did not accept
regulatory support successfully received IRB approval. Providing regulatory
support, particularly to trainees and junior faculty, may be associated with
better success in obtaining IRB approval as well as preventing the unnecessary
submission of projects that are not research and would therefore not require IRB
review or approval.
PMID- 29345181
TI - Corrigendum.
PMID- 29345180
TI - Depression Among Caregivers of Patients With Dementia.
AB - We aimed to assess depressive symptoms in caregivers of patients with dementia,
taking into account variables such as severity of dementia, sex, age, and
financial state of the patient. We recruited 222 caregivers of patients with
dementia from King Abdulaziz Medical City, Saudi Alzheimer's Disease Association,
and online, from February to June 2017, and employed the Patient Health
Questionnaire to assess depression, and the Blessed Dementia Scale to assess
severity of dementia. The prevalence of clinical depression among the caregivers
was 14.9%. Minimal symptoms of depression were experienced by 96 caregivers
(43.2%), moderate by 45 (20.3%), moderate-severe by 15 (6.8%), and severe by 8
(3.6%). Forty-six patients had mild dementia (22%), 73 had moderate (34.9%), and
90 had severe (43.1%). Caregivers of patients with dementia experience
considerable burden and lower level of health-related quality of life and may be
predisposed to developing clinical depression.
PMID- 29345182
TI - Breast cancer screening among shift workers: a nationwide population-based survey
in Korea.
AB - We aimed to examine the association between shift work types and participation in
breast cancer screening (BCS) programs by comparing rates of participation for
BCS among regular daytime workers and alternative shift workers using data from a
nationally representative, population-based survey conducted in Korea. In
addition, the results were analyzed according to sociodemographic factors,
including occupation, education, income, private health insurance, age, and
number of working hours a week. This secondary cross-sectional analysis used data
from the 2012 Korean National Health and Nutritional Examination Survey. The
target population included women aged >= 40 years who responded as to whether
they had undergone BCS in the previous year. Accordingly, we analyzed survey data
for a total of 1,193 women and used a multivariate logistic regression analysis
to evaluate the differences in factors affecting BCS between regular daytime and
alternative shift workers. A logistic regression analysis was performed
considering private health insurance as a significant sociodemographic factor for
BCS among regular daytime shift workers. In contrast, none of the tested
variables could significantly predict adherence to BCS among alternative shift
workers. The results of this study suggest the need for the development of
comprehensive workplace breast cancer prevention programs by considering shift
work types. More attention should be given to female workers with low education
levels, those who are uninsured, and young workers to improve the participation
rate for BCS at the workplace.
PMID- 29345184
TI - Temperature-dependent small RNA expression in Drosophila melanogaster.
AB - Temperature has a major impact on gene expression in ectotherms. But until
recently, it was not clear in which way, if any, small non-coding RNAs such as
miRNAs or piRNAs contribute to thermosensitive gene regulation. We have recently
shown that temperature-responsive miRNAs in Drosophila drive adaptation to
different ambient temperatures on the transcriptome level. Moreover, we
demonstrated that higher temperatures lead to a more efficient piRNA-dependent
transposon silencing, possibly due to heat-induced unfolding of RNA secondary
structures. In this commentary, we will dwell upon particular interesting aspects
connected to our findings, hoping that our point of view may encourage other
scientists to address some of the questions raised here. We will particularly
focus on aspects related to climate-dependent transposon propagation in evolution
and putative transgenerational epigenetic effects of altered small RNA
transcriptomes. We further briefly indicate how temperature-responsive miRNAs may
confound the interpretation of data obtained from experiments comprising heat
shock treatment which is a widely used technique not only in Drosophila genetics.
PMID- 29345186
TI - Response to Commentary: Regulatory Support Improves Subsequent IRB Approval Rates
in Studies Initially Deemed Not Ready for Review-A CTSA Institution's Experience.
PMID- 29345187
TI - The formation of a medical student research committee and its impact on
involvement in departmental research.
AB - : Over the past ten years, medical students have increased their research
activity to be competitive for orthopaedic residency positions throughout the
country. This increase may favor students at institutions with a strong history
of research production and well-established research departments with supporting
staff. To compete with these institutions, a Musculoskeletal Research Committee
was developed at a southern academic institution to provide a mutually beneficial
link between orthopaedic research faculty and medical students. This manuscript
describes the formation of this committee and the resultant involvement of young
medical students in departmental research over a one year period. Composed of
students and faculty, the committee developed a Research Guide for Medical
Students, Research Database and Student List, Medical Students' Webpage, and
Routing Form, and holds quarterly meetings for those students active in
orthopaedic research. With this platform, the committee aimed to increase young
student involvement in research and provide a stratified level of study
participation among upper-level students for continued mentorship. In one
calendar year, the total number of first and second-year students participating
in department research increased 460% (5 to 28). Also, the total number of
research projects with student involvement from these two classes increased 780%
(5 to 44). The introduction of a research committee is an effective method of
stimulating student interest in departmental research. Early participation
results are promising, and this method may be applicable to other departments and
institutions hoping to increase research productivity. ABBREVIATIONS: IRB:
Institutional Review Board.
PMID- 29345188
TI - Arsenic removal from alkaline leaching solution using Fe (III) precipitation.
AB - The alkaline leaching solution from arsenic-containing gold concentrate contains
a large amount of arsenate ions, which should be removed because it is harmful to
the production process and to the environment. In this study, conventional Fe
(III) precipitation was used to remove arsenic from the leaching solution. The
precipitation reaction was carried out at the normal temperature, and the effects
of pH value and Fe/As ratio on the arsenic removal were investigated. The results
show that the removal rate of arsenic is distinctive at different pH values, and
the effect is best within the pH range of 5.25-5.96. The removal rate can be
further increased by increasing the ratio of Fe/As. When the pH = 5.25-5.96 and
Fe/As > 1.8, the arsenic in the solution can be reduced to below 5 mg/L. However,
the crystallinity of ferric arsenate is poor, and the particle size is small,
most of which is about 1 MUm. The leaching toxicity test shows the leaching
toxicity of precipitates gradually decreased by the increase of Fe/As. The
precipitates can be stored safely as the ratio of Fe/As exceeded 2.5.
PMID- 29345185
TI - Drugging tRNA aminoacylation.
AB - Inhibition of tRNA aminoacylation has proven to be an effective antimicrobial
strategy, impeding an essential step of protein synthesis. Mupirocin, the well
known selective inhibitor of bacterial isoleucyl-tRNA synthetase, is one of three
aminoacylation inhibitors now approved for human or animal use. However, design
of novel aminoacylation inhibitors is complicated by the steadfast requirement to
avoid off-target inhibition of protein synthesis in human cells. Here we review
available data regarding known aminoacylation inhibitors as well as key amino
acid residues in aminoacyl-tRNA synthetases (aaRSs) and nucleotides in tRNA that
determine the specificity and strength of the aaRS-tRNA interaction. Unlike most
ligand-protein interactions, the aaRS-tRNA recognition interaction represents
coevolution of both the tRNA and aaRS structures to conserve the specificity of
aminoacylation. This property means that many determinants of tRNA recognition in
pathogens have diverged from those of humans-a phenomenon that provides a
valuable source of data for antimicrobial drug development.
PMID- 29345189
TI - MicroRNA-19 contributes to the malignant phenotypes of osteosarcoma in vitro by
targeting Pax6.
AB - This study was conducted to detect the expression of miR-19 and Pax6 (Paired box
protein 6) in human osteosarcoma cells and the effects on biological
characteristics of osteosarcoma cells. Quantitative real-time polymerase chain
reaction was used to detect the expression of Pax6 and miR-19 in normal human
osteoblasts (hFOB 1.19) and osteosarcoma cell lines (U2OS, Saos-2, and MG-63).
Results showed that miR-19 was significantly upregulated in osteosarcoma cell
lines compared with that in hFOB 1.19 cells, while the expression of Pax6
messenger RNA was significantly downregulated. Pax6 was defined as the target
gene of miR-19 which was validated by luciferase reporter gene analysis. Results
indicated that miR-19 had an interaction with Pax6 3'-untranslated region. At the
same time, the protein expression of Pax6 was significantly decreased in the MG
63 cells transfected with miR-19 mimic and was notably enhanced in osteosarcoma
MG-63 cells transfected with miR-19 inhibitor. These data suggested that Pax6 was
a target of miR-19 in osteosarcoma MG-63 cells. The effects of miR-19 on the
biological behavior of MG-63 cells were determined by 3-(4,5-dimethylthiazol-2
yl)-2,5-diphenyltetrazolium bromide, flow cytometry, and Transwell assay. Results
showed that the downregulation of miR-19 inhibited cell viability, reduced the
percentage of cells in S phase and the number of cells passing through the
Transwell chamber, and increased the number of apoptotic cells. Western blot
analysis showed that the inhibition of miR-19 significantly increased the
expression of epithelial proteins (E-cadherin and beta-catenin) and decreased the
expression of mesenchymal protein (Vimentin), extracellular signal-regulated
kinase, and phosphorylated extracellular signal-regulated kinase in MG-63 cells.
MiR-19 inhibitor and Pax6 small interfering RNA were simultaneously transfected
into MG-63 cells. Results from 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide, flow cytometry, and Transwell assay demonstrated
that the inhibition of Pax6 expression in MG-63 cells could reverse the cell
biological effects induced by the inhibition of miR-19 expression. Based on these
findings, it was suggested that miR-19, upregulated in osteosarcoma cells,
negatively regulated the expression of Pax6, which can promote the malignant
phenotypes of osteosarcoma cells via activation of the extracellular signal
regulated kinase signaling pathways. Therefore, miR-19/Pax6 may offer potential
for use as a target for the treatment of osteosarcoma.
PMID- 29345191
TI - Enhanced sulfide removal and bioelectricity generation in microbial fuel cells
with anodes modified by vertically oriented nanosheets.
AB - Anode materials and structures are of critical importance for microbial fuel
cells (MFCs) recovering energy from toxic substrates. Carbon-fiber-felt anodes
modified by layers of vertically oriented TiO2 and Fe2O3 nanosheets were applied
in the present study. Enhanced sulfide removal efficiencies (both over 90%) were
obtained after a 48-h operation, with maximum power densities improved by 1.53
and 1.36 folds compared with MFCs with raw carbon-fiber-felt anode. The modified
anodes provided more active sites for microbial adhesion with increasing biomass
densities. High-throughput 16S rRNA gene sequencing analysis also indicated the
increase in microbial diversities. Bacteroidetes responsible for bioelectricity
generation with Thiobacillus and Spirochaeta dominating sulfide removal were
found in the MFCs with the modified anodes, with less anaerobic fermentative
bacteria as Firmicutes appeared. This indicates that the proposed materials are
competitive for applications of MFCs generating bioelectricity from toxic
sulfide.
PMID- 29345190
TI - Magnetoelectric nanoparticles for delivery of antitumor peptides into
glioblastoma cells by magnetic fields.
AB - AIM: We studied externally controlled anticancer effects of binding tumor growth
inhibiting synthetic peptides to magnetoelectric nanoparticles (MENs) on
treatment of glioblastomas. METHODS: Hydrothermally synthesized 30-nm MENs had
the core-shell composition of CoFe2O4@BaTiO3. Molecules of growth hormone
releasing hormone antagonist of the MIA class (MIA690) were chemically bound to
MENs. In vitro experiments utilized human glioblastoma cells (U-87MG) and human
brain microvascular endothelial cells. RESULTS: The studies demonstrated
externally controlled high-efficacy binding of MIA690 to MENs, targeted
specificity to glioblastoma cells and on-demand release of the peptide by
application of d.c. and a.c. magnetic fields, respectively. CONCLUSION: The
results support the use of MENs as an effective drug delivery carrier for growth
hormone-releasing hormone antagonists in the treatment of human glioblastomas.
PMID- 29345192
TI - Cross-validation of the Dot Counting Test in a large sample of credible and non
credible patients referred for neuropsychological testing.
AB - OBJECTIVE: To cross-validate the Dot Counting Test in a large neuropsychological
sample. METHOD: Dot Counting Test scores were compared in credible (n = 142) and
non-credible (n = 335) neuropsychology referrals. RESULTS: Non-credible patients
scored significantly higher than credible patients on all Dot Counting Test
scores. While the original E-score cut-off of >=17 achieved excellent specificity
(96.5%), it was associated with mediocre sensitivity (52.8%). However, the cut
off could be substantially lowered to >=13.80, while still maintaining adequate
specificity (>=90%), and raising sensitivity to 70.0%. Examination of non
credible subgroups revealed that Dot Counting Test sensitivity in feigned mild
traumatic brain injury (mTBI) was 55.8%, whereas sensitivity was 90.6% in
patients with non-credible cognitive dysfunction in the context of claimed
psychosis, and 81.0% in patients with non-credible cognitive performance in
depression or severe TBI. Thus, the Dot Counting Test may have a particular role
in detection of non-credible cognitive symptoms in claimed psychiatric disorders.
Alternative to use of the E-score, failure on >=1 cut-offs applied to individual
Dot Counting Test scores (>=6.0" for mean grouped dot counting time, >=10.0" for
mean ungrouped dot counting time, and >=4 errors), occurred in 11.3% of the
credible sample, while nearly two-thirds (63.6%) of the non-credible sample
failed one of more of these cut-offs. CONCLUSIONS: An E-score cut-off of 13.80,
or failure on >=1 individual score cut-offs, resulted in few false positive
identifications in credible patients, and achieved high sensitivity (64.0-70.0%),
and therefore appear appropriate for use in identifying neurocognitive
performance invalidity.
PMID- 29345193
TI - Serotonin 2A receptor inhibition protects against the development of pulmonary
hypertension and pulmonary vascular remodeling in neonatal mice.
AB - Pulmonary hypertension (PH) complicating bronchopulmonary dysplasia (BPD) worsens
clinical outcomes in former preterm infants. Increased serotonin (5
hydroxytryptamine, 5-HT) signaling plays a prominent role in PH pathogenesis and
progression in adults. We hypothesized that increased 5-HT signaling contributes
to the pathogenesis of neonatal PH, complicating BPD and neonatal lung injury.
Thus, we investigated 5-HT signaling in neonatal mice exposed to bleomycin,
previously demonstrated to induce PH and alveolar simplification. Newborn wild
type mice received intraperitoneal PBS, ketanserin (1 mg/kg), bleomycin (3 U/kg)
or bleomycin (3 U/kg) plus ketanserin (1 mg/kg) three times weekly for 3 wk.
Following treatment with bleomycin, pulmonary expression of the rate-limiting
enzyme of 5-HT synthesis, tryptophan hydroxylase-1 (Tph1), was significantly
increased. Bleomycin did not affect pulmonary 5-HT 2A receptor (R) expression,
but did increase pulmonary gene expression of the 5-HT 2BR and serotonin
transporter. Treatment with ketanserin attenuated bleomycin-induced PH (increased
RVSP and RVH) and pulmonary vascular remodeling (decreased vessel density and
increased muscularization of small vessels). In addition, we found that treatment
with ketanserin activated pulmonary MAPK and Akt signaling in mice exposed to
bleomycin. We conclude that 5-HT signaling is increased in a murine model of
neonatal PH and pharmacological inhibition of the 5-HT 2AR protects against the
development of PH in neonatal lung injury. We speculate this occurs through
restoration of MAPK signaling and increased Akt signaling.
PMID- 29345194
TI - Transient stretch induces cytoskeletal fluidization through the severing action
of cofilin.
AB - With every deep inspiration (DI) or sigh, the airway wall stretches, as do the
airway smooth muscle cells in the airway wall. In response, the airway smooth
muscle cell undergoes rapid stretch-induced cytoskeletal fluidization. As a
molecular mechanism underlying the cytoskeletal fluidization response, we
demonstrate a key role for the actin-severing protein cofilin. Using primary
human airway smooth muscle cells, we simulated a DI by imposing a transient
stretch of physiological magnitude and duration. We used traction microscopy to
measure the resulting changes in contractile forces. After a transient stretch,
cofilin-knockdown cells exhibited a 29 +/- 5% decrease in contractile force
compared with prestretch conditions. By contrast, control cells exhibited a 67 +/
6% decrease ( P < 0.05, knockdown vs. control). Consistent with these
contractile force changes with transient stretch, actin filaments in cofilin
knockdown cells remained largely intact, whereas actin filaments in control cells
were rapidly disrupted. Furthermore, in cofilin-knockdown cells, contractile
force at baseline was higher and rate of remodeling poststretch was slower than
in control cells. Additionally, the severing action of cofilin was restricted to
the release phase of the transient stretch. We conclude that the actin-severing
activity of cofilin is an important factor in stretch-induced cytoskeletal
fluidization and may account for an appreciable part of the bronchodilatory
effects of a DI.
PMID- 29345196
TI - Surfactant protein C dampens inflammation by decreasing JAK/STAT activation
during lung repair.
AB - Surfactant protein C (SPC), a key component of pulmonary surfactant, also plays a
role in regulating inflammation. SPC deficiency in patients and mouse models is
associated with increased inflammation and delayed repair, but the key drivers of
SPC-regulated inflammation in response to injury are largely unknown. This study
focuses on a new mechanism of SPC as an anti-inflammatory molecule using SPC
TK/SPC-KO (surfactant protein C-thymidine kinase/surfactant protein C knockout)
mice, which represent a novel sterile injury model that mimics clinical acute
respiratory distress syndrome (ARDS). SPC-TK mice express the inducible suicide
gene thymidine kinase from by the SPC promoter, which targets alveolar type 2
(AT2) cells for depletion in response to ganciclovir (GCV). We compared GCV
induced injury and repair in SPC-TK mice that have normal endogenous SPC
expression with SPC-TK/SPC-KO mice lacking SPC expression. In contrast to SPC-TK
mice, SPC-TK/SPC-KO mice treated with GCV exhibited more severe inflammation,
resulting in over 90% mortality; there was only 8% mortality of SPC-TK animals.
SPC-TK/SPC-KO mice had highly elevated inflammatory cytokines and granulocyte
infiltration in the bronchoalveolar lavage (BAL) fluid. Consistent with a
proinflammatory phenotype, immunofluorescence revealed increased phosphorylated
signal transduction and activation of transcription 3 (pSTAT3), suggesting
enhanced Janus kinase (JAK)/STAT activation in inflammatory and AT2 cells of SPC
TK/SPC-KO mice. The level of suppressor of cytokine signaling 3, an anti
inflammatory mediator that decreases pSTAT3 signaling, was significantly
decreased in the BAL fluid of SPC-TK/SPC-KO mice. Hyperactivation of pSTAT3 and
inflammation were rescued by AZD1480, a JAK1/2 inhibitor. Our findings showing a
novel role for SPC in regulating inflammation via JAK/STAT may have clinical
applications.
PMID- 29345197
TI - Neonatal hyperoxia depletes pulmonary vein cardiomyocytes in adult mice via
mitochondrial oxidation.
AB - Supplemental oxygen given to preterm infants has been associated with permanently
altering postnatal lung development. Now that these individuals are reaching
adulthood, there is growing concern that early life oxygen exposure may also
promote cardiovascular disease through poorly understood mechanisms. We
previously reported that adult mice exposed to 100% oxygen between postnatal days
0 and 4 develop pulmonary hypertension, defined pathologically by capillary
rarefaction, dilation of arterioles and veins, cardiac failure, and a reduced
lifespan. Here, Affymetrix Gene Arrays are used to identify early transcriptional
changes that take place in the lung before pulmonary capillary rarefaction. We
discovered neonatal hyperoxia reduced expression of cardiac muscle genes,
including those involved in contraction, calcium signaling, mitochondrial
respiration, and vasodilation. Quantitative RT-PCR, immunohistochemistry, and
genetic lineage mapping using Myh6CreER; Rosa26RmT/mG mice revealed this
reflected loss of pulmonary vein cardiomyocytes. The greatest loss of
cadiomyocytes was seen within the lung followed by a graded loss beginning at the
hilum and extending into the left atrium. Loss of these cells was seen by 2 wk of
age in mice exposed to >=80% oxygen and was attributed, in part, to reduced
proliferation. Administering mitoTEMPO, a scavenger of mitochondrial superoxide
during neonatal hyperoxia prevented loss of these cells. Since pulmonary vein
cardiomyocytes help pump oxygen-rich blood out of the lung, their early loss
following neonatal hyperoxia may contribute to cardiovascular disease seen in
these mice, and perhaps in people who were born preterm.
PMID- 29345195
TI - Mitochondrial dysfunction and pulmonary hypertension: cause, effect, or both.
AB - Pulmonary hypertension describes a heterogeneous disease defined by increased
pulmonary artery pressures, and progressive increase in pulmonary vascular
resistance due to pathologic remodeling of the pulmonary vasculature involving
pulmonary endothelial cells, pericytes, and smooth muscle cells. This process
occurs under various conditions, and although these populations vary, the
clinical manifestations are the same: progressive dyspnea, increases in right
ventricular (RV) afterload and dysfunction, RV-pulmonary artery uncoupling, and
right-sided heart failure with systemic circulatory collapse. The overall
estimated 5-yr survival rate is 72% in highly functioning patients, and as low as
28% for those presenting with advanced symptoms. Metabolic theories have been
suggested as underlying the pathogenesis of pulmonary hypertension with growing
evidence of the role of mitochondrial dysfunction involving the major proteins of
the electron transport chain, redox-related enzymes, regulators of the proton
gradient and calcium homeostasis, regulators of apoptosis, and mitophagy. There
remain more studies needed to characterize mitochondrial dysfunction leading to
impaired vascular relaxation, increase proliferation, and failure of regulatory
mechanisms. The effects on endothelial cells and resulting interactions with
their microenvironment remain uncharted territory for future discovery.
Additionally, on the basis of observations that the "plexigenic lesions" of
pulmonary hypertension resemble the unregulated proliferation of tumor cells,
similarities between cancer pathobiology and pulmonary hypertension have been
drawn, suggesting interactions between mitochondria and angiogenesis. Recently,
mitochondria targeting has become feasible, which may yield new therapeutic
strategies. We present a state-of-the-art review of the role of mitochondria in
both the pathobiology of pulmonary hypertension and potential therapeutic targets
in pulmonary vascular processes.
PMID- 29345199
TI - Pulmonary vascular dysfunction secondary to pulmonary arterial hypertension:
insights gained through retrograde perfusion.
AB - Here, we tested the hypothesis that severe pulmonary arterial hypertension
impairs retrograde perfusion. To test this hypothesis, pulmonary arterial
hypertension was induced in Fischer rats using a single injection of Sugen 5416
followed by 3 wk of exposure to 10% hypoxia and then 2 wk of normoxia. This Sugen
5416 and hypoxia regimen caused severe pulmonary arterial hypertension, with a
Fulton index of 0.73 +/- 0.07, reductions in both the pulmonary arterial
acceleration time and pulmonary arterial acceleration to pulmonary arterial
ejection times ratio, and extensive medial hypertrophy and occlusive neointimal
lesions. Whereas the normotensive circulation accommodated large increases in
forward and retrograde flow, the hypertensive circulation did not. During forward
flow, pulmonary artery and double occlusion pressures rose sharply at low
perfusion rates, resulting in hydrostatic edema. Pulmonary arterial hypertensive
lungs possessed an absolute intolerance to retrograde perfusion, and they rapidly
developed edema. Retrograde perfusion was not rescued by maximal vasodilation.
Retrograde perfusion was preserved in lungs from animals treated with Sugen 5416
and hypoxia for 1 and 3 wk, in lungs from animals with a milder form of hypoxic
hypertension, and in normotensive lungs subjected to high outflow pressures. Thus
impaired retrograde perfusion coincides with development of severe pulmonary
arterial hypertension, with advanced structural defects in the microcirculation.
PMID- 29345200
TI - Distinct niches within the extracellular matrix dictate fibroblast function in
(cell free) 3D lung tissue cultures.
AB - Cues from the extracellular matrix (ECM) and their functional interplay with
cells play pivotal roles for development, tissue repair, and disease. However,
the precise nature of this interplay remains elusive. We used an innovative 3D
cell culture ECM model by decellularizing 300-um-thick ex vivo lung tissue
scaffolds (d3D-LTCs) derived from diseased and healthy mouse lungs, which widely
mimics the native (patho)physiological in vivo ECM microenvironment. We
successfully repopulated all d3D-LTCs with primary human and murine fibroblasts,
and moreover, we demonstrated that the cells also populated the innermost core
regions of the d3D-LTCs in a real 3D fashion. The engrafted fibroblasts revealed
a striking functional plasticity, depending on their localization in distinct ECM
niches of the d3D-LTCs, affecting the cells' tissue engraftment, cellular
migration rates, cell morphologies, and protein expression and phosphorylation
levels. Surprisingly, we also observed fibroblasts that were homing to the lung
scaffold's interstitium as well as fibroblasts that were invading fibrotic areas.
To date, the functional nature and even the existence of 3D cell matrix adhesions
in vivo as well as in 3D culture models is still unclear and controversial. Here,
we show that attachment of fibroblasts to the d3D-LTCs evidently occurred via
focal adhesions, thus advocating for a relevant functional role in vivo.
Furthermore, we found that protein levels of talin, paxillin, and zyxin and
phosphorylation levels of paxillin Y118, as well as the migration-relevant small
GTPases RhoA, Rac, and CDC42, were significantly reduced compared with their
attachment to 2D plastic dishes. In summary, our results strikingly indicate that
inherent physical or compositional characteristics of the ECM act as instructive
cues altering the functional behavior of engrafted cells. Thus, d3D-LTCs might
aid to obtain more realistic data in vitro, with a high relevance for drug
discovery and mechanistic studies alike.
PMID- 29345198
TI - Fibrin turnover and pleural organization: bench to bedside.
AB - Recent studies have shed new light on the role of the fibrinolytic system in the
pathogenesis of pleural organization, including the mechanisms by which the
system regulates mesenchymal transition of mesothelial cells and how that process
affects outcomes of pleural injury. The key contribution of plasminogen activator
inhibitor-1 to the outcomes of pleural injury is now better understood as is its
role in the regulation of intrapleural fibrinolytic therapy. In addition, the
mechanisms by which fibrinolysins are processed after intrapleural administration
have now been elucidated, informing new candidate diagnostics and therapeutics
for pleural loculation and failed drainage. The emergence of new potential
interventional targets offers the potential for the development of new and more
effective therapeutic candidates.
PMID- 29345201
TI - Clinical validation of nuclear factor kappa B expression in invasive breast
cancer.
AB - Breast cancer is the most commonly diagnosed cancer in Polish women. The
expression of transcription nuclear factor kappa B, a key inducer of inflammatory
response promoting carcinogenesis and cancer progression in breast cancer, is not
well-established. We assessed the nuclear factor kappa B expression in a total of
119 invasive breast carcinomas and 25 healthy control samples and correlated this
expression pattern with several clinical and pathologic parameters including
histologic type and grade, tumor size, lymph node status, estrogen receptor
status, and progesterone receptor status. The data used for the analysis were
derived from medical records. An immunohistochemical analysis of nuclear factor
kappa B, estrogen receptor, and progesterone receptor was carried out and
evaluation of stainings was performed. The expression of nuclear factor kappa B
was significantly higher than that in the corresponding healthy control samples.
No statistical difference was demonstrated in nuclear factor kappa B expression
in relation to age, menopausal status, lymph node status, tumor size and
location, grade and histologic type of tumor, and hormonal status (estrogen
receptor and progesterone receptor). Nuclear factor kappa B is significantly
overexpressed in invasive breast cancer tissues. Although nuclear factor kappa B
status does not correlate with clinicopathological findings, it might provide
important additional information on prognosis and become a promising object for
targeted therapy.
PMID- 29345202
TI - Qualitative and semiquantitative analysis of the protein coronas associated to
different functionalized nanoparticles.
AB - AIM: The investigation on protein coronas (PCs) adsorbed onto nanoparticle (NP)
surface is representing an open issue due to difficulties in detection and clear
isolation of the adsorbed proteins. In this study, we investigated protocols able
to isolate the compositions of PCs of three polymeric NPs. MATERIALS & METHODS:
Unfunctionalized NPs and two functionalized NPs were considered as proof-of
concept for the qualitative and semiquantitative analysis of both the corona
levels (stably or weakly adsorbed coronas [SC/WC]) of these different
nanocarriers. RESULTS: The protocols applied were able to discriminate between
the SC and WC. In particular, experimental results indicated that stably adsorbed
coronas are prevalently composed by ApoE, while WC by albumin in all the NPs.
Otherwise, some differences in WC could be correlated with surface
functionalization. CONCLUSION: This experimental approach allows characterizing
the whole PCs, proposing a protocol for isolation of different types of proteins
composing PCs.
PMID- 29345203
TI - Illusionary Science?
PMID- 29345205
TI - Update on Lateral Ankle Instability.
PMID- 29345206
TI - Successful treatment of refractory autoimmune hemolytic anemia after allogeneic
hematopoietic stem cell transplantation with bortezomib.
PMID- 29345208
TI - Top-rated AMEE MedEdPublish Papers - September 2017.
PMID- 29345207
TI - Thresholds and interpretations: How clinical competency committees identify
pediatric residents with performance concerns.
AB - BACKGROUND: Clinical competency committee (CCC) identification of residents with
performance concerns is critical for early intervention. METHODS: Program
directors and 94 CCC members at 14 pediatric residency programs responded to a
written survey prompt asking them to describe how they identify residents with
performance concerns. Data was analyzed using thematic analysis. RESULTS: Six
themes emerged from analysis and were grouped into two domains. The first domain
included four themes, each describing a path through which residents could meet
or exceed a concern threshold:1) written comments from rotation assessments are
foundational in identifying residents with performance concerns, 2) concerning
performance extremes stand out, 3) isolated data points may accumulate to raise
concern, and 4) developmental trajectory matters. The second domain focused on
how CCC members and program directors interpret data to make decisions about
residents with concerns and contained 2 themes: 1) using norm- and/or criterion
referenced interpretation, and 2) assessing the quality of the data that is
reviewed. CONCLUSIONS: Identifying residents with performance concerns is
important for their education and the care they provide. This study delineates
strategies used by CCC members across several programs for identifying these
residents, which may be helpful for other CCCs to consider in their efforts.
PMID- 29345209
TI - Medical Teacher in Ten Minutes.
PMID- 29345210
TI - The impact of time from diagnosis to treatment in diffuse large B-cell lymphoma.
AB - Diffuse large B-cell lymphoma (DLBCL) is a high-grade lymphoma that requires
treatment. We retrospectively analyzed the impact of time from diagnosis-to
treatment (TDT) on progression-free survival (PFS) and overall survival (OS) in
581 R-CHOP-treated patients. TDT was defined as the interval between diagnostic
biopsy date and day 1 R-CHOP. Cox regression showed stage 3-4 disease (p = .01)
and longer TDT (HR 1.13, p =.031) were associated with shorter OS. Eastern
Cooperative Oncology Group >=2 (p = .02), stage 3-4 disease (p < .001), and
longer TDT (HR 1.12, p = .028) predicted shorter PFS. The significant
interactions between TDT with lactate dehydrogenase (LDH) and with disease stage
prompted separate analyses in high versus normal LDH, and stage 3-4 versus 1-2
disease. Longer TDT was associated with shortened PFS and OS only with advanced
stage, and, if high LDH was present. Treatment should be started as early as
possible for high-tumor burden disease. Delaying treatment in patients with early
stage or low LDH does not seem harmful.
PMID- 29345211
TI - Developing single-entity theranostic: drug-based fluorescent nanoclusters with
augmented cytotoxicity.
AB - AIM: To develop methotrexate (MTX) templated luminescent gold nanoclusters (NCs)
as a single unit nanotheranostic for cancer therapy and to assess its potential
as an alternative to the parent drug, for drug delivery vehicles (DDVs). METHODS:
Theranostics were synthesized and extensively characterized. The stability of the
theranostic and its bioimaging aptitude were evaluated. The antiproliferative
propensity of the theranostic was gauged with cell viability assays and was
supplemented with cytometry-based assays. Feasibility of delivering the MTX NCs
instead of parent drug on a DDV was also checked. RESULTS: MTX NCs displayed
remarkable physical characteristics and augmented cytotoxicity with a robust
stability in phosphate-buffered saline and serum. MTX NCs also demonstrated their
amenability to being loaded on a DDV (chitosan folic acid nanoparticles) while
retaining their physical and cytotoxic profile. CONCLUSION: Generation of next
level drug-based theranostics with the potential of replacing the free drug in
drug delivery platforms.
PMID- 29345212
TI - Prioritising action to accelerate gender equity and health for women and girls:
Microdata analysis of 47 countries.
AB - The Sustainable Development Goals set ambitious targets for health. Meeting such
will require drastic improvements in the social conditions for women and girls.
Understanding which social conditions have the greatest impact on health can help
prioritise action, yet there is little comparative data. We use microdata from
338,580 women in 47 low- and middle-income countries to estimate the relative
contributions of improved social determinants in bringing about maternal and
child health gains over the past 20 years. Regression analyses examine
determinants related to education, work, health services, family, and violence;
the potential health benefit that could be derived from improving conditions is
calculated. Secondary education and child marriage emerge as the strongest and
most consistent predictors of health. The largest impact is seen on adolescent
births: we estimate that achieving universal completion of secondary schooling
for young women could lower adolescent births by 18 percentage points;
eliminating child marriages could lower adolescent births by 11 points.
Intervening in these two areas could also bring about substantial reductions in
the unmet need for family planning, past-year intimate partner violence, and
child mortality. Thus, we suggest prioritising policies targeting secondary
education and child marriage in order to accelerate gender equity and health.
PMID- 29345213
TI - Matcha Green Tea Drinks Enhance Fat Oxidation During Brisk Walking in Females.
AB - Intake of the catechin epigallocatechin gallate and caffeine has been shown to
enhance exercise-induced fat oxidation. Matcha green tea powder contains
catechins and caffeine and is consumed as a drink. We examined the effect of
Matcha green tea drinks on metabolic, physiological, and perceived intensity
responses during brisk walking. A total of 13 females (age: 27 +/- 8 years, body
mass: 65 +/- 7 kg, height: 166 +/- 6 cm) volunteered to participate in the study.
Resting metabolic equivalent (1-MET) was measured using Douglas bags (1-MET: 3.4
+/- 0.3 ml.kg-1.min-1). Participants completed an incremental walking protocol to
establish the relationship between walking speed and oxygen uptake and
individualize the walking speed at 5- or 6-MET. A randomized, crossover design
was used with participants tested between Days 9 and 11 of the menstrual cycle
(follicular phase). Participants consumed three drinks (each drink made with 1 g
of Matcha premium grade; OMGTea Ltd., Brighton, UK) the day before and one drink
2 hr before the 30-min walk at 5- (n = 10) or 6-MET (walking speed: 5.8 +/- 0.4
km/hr) with responses measured at 8-10, 18-20, and 28-30 min. Matcha had no
effect on physiological and perceived intensity responses. Matcha resulted in
lower respiratory exchange ratio (control: 0.84 +/- 0.04; Matcha: 0.82 +/- 0.04;
p < .01) and enhanced fat oxidation during a 30-min brisk walk (control: 0.31 +/-
0.10; Matcha: 0.35 +/- 0.11 g/min; p < .01). Matcha green tea drinking can
enhance exercise-induced fat oxidation in females. However, when regular brisk
walking with 30-min bouts is being undertaken as part of a weight loss program,
the metabolic effects of Matcha should not be overstated.
PMID- 29345214
TI - Deciding to adopt revised and new psychological and neuropsychological tests: an
inter-organizational position paper.
AB - OBJECTIVE: Neuropsychological tests undergo periodic revision intended to improve
psychometric properties, normative data, relevance of stimuli, and ease of
administration. In addition, new tests are developed to evaluate psychological
and neuropsychological constructs, often purporting to improve evaluation
effectiveness. However, there is limited professional guidance to
neuropsychologists concerning the decision to adopt a revised version of a test
and/or replace an older test with a new test purporting to measure the same or
overlapping constructs. This paper describes ethical and professional issues
related to the selection and use of older versus newer psychological and
neuropsychological tests, with the goal of promoting appropriate test selection
and evidence-based decision making. METHOD: Ethical and professional issues were
reviewed and considered. CONCLUSIONS: The availability of a newer version of a
test does not necessarily render obsolete prior versions of the test for purposes
that are empirically supported, nor should continued empirically supported use of
a prior version of a test be considered unethical practice. Until a revised or
new test has published evidence of improved ability to help clinicians to make
diagnostic determinations, facilitate treatment, and/or assess change over time,
the choice to delay adoption of revised or new tests may be viewed as reasonable
and appropriate. Recommendations are offered to facilitate decisions about the
adoption of revised and new tests. Ultimately, it is the responsibility of
individual neuropsychologists to determine which tests best meet their patients'
needs, and to be able to support their decisions with empirical evidence and
sound clinical judgment.
PMID- 29345215
TI - Relationship of "weekend warrior" and regular physical activity patterns with
metabolic syndrome and its associated diseases among Chinese rural adults.
AB - : Little is known about the "weekend warrior" pattern of physical activity (PA)
where people perform all their PA in 1 or 2 sessions per week. We investigated
the relationship of weekend warrior and other PA patterns with metabolic syndrome
(MS) and its associated diseases. Data on sociodemographic and lifestyle
characteristics were collected from the Nantong Metabolic Syndrome Study that
included 13,505 women and 6,997 men between 2007 and 2008. Compared with inactive
participants, weekend warriors were at lower risk of MS, diabetes, and
hypertension; respective odds ratios (95% confidence intervals) for men and women
were 0.58 (0.43-0.79) and 0.67 (0.52-0.86), 0.52 (0.34-0.79) and 0.52 (0.33
0.83), and 0.79 (0.63-0.99) and 0.71 (0.57-0.89). Similar results were observed
with regular activity, at a frequency of >3 sessions per week. Both weekend
warrior and regular PA patterns showed a 10-60% decrease in abnormal
triglycerides, glucose, and blood pressure in both sexes; abnormal waist
circumference in men only; and abnormal high-density lipoprotein in women only.
Our observed cross-sectional relationships reflect that >150 min/week of moderate
PA or 75 min/week vigorous-intensity PA is needed to prevent MS and its component
diseases, even if in a short-bout, intermittent PA pattern. ABBREVIATIONS: MS:
Metabolic syndrome; WC: Waist circumference; TG: Triglycerides; HDL-c: High
density lipoprotein cholesterol; BP: Blood pressure; SBP: Systolic blood
pressure, DBP: Diastolic blood pressure; PA: Physical activity; JIS: Joint
Interim Statement; CVD: Cardiovascular disease; ATP III: US Third Report of the
National Cholesterol Education Program, the Adult Treatment Panel; IDF:
International Diabetes Federation; IPAQ: International Physical Activity
Questionnaire; BMI: Body mass index; CDC: the Nantong Centers for Disease
Control; OR: Odds ratio; CI: Confidence interval; SD: Standard deviation; IQR:
Interquartile range.
PMID- 29345216
TI - A Novel System for Assessing Facial Muscle Movements: The Facegram 3D.
PMID- 29345217
TI - Statistical analysis of human microarray data shows that dietary intervention
with n-3 fatty acids, flavonoids and resveratrol enriches for immune response and
disease pathways.
AB - n-3 Fatty acids, flavonoids and resveratrol are well publicised for their
beneficial effects on human health and wellbeing. Identifying common, underlying
biological mechanisms targeted by these functional foods would therefore be
informative for the public health sector for advising on nutritional health and
disease, food and drug product development and consumer interest. The aim of this
study was to explore the potential effects of gene expression changes associated
with n-3 fatty acids EPA and DHA, flavonoids and resveratrol on modifying
biological systems and disease pathways. To test this, publicly available human
microarray data for significant gene expression changes associated with dietary
intervention with EPA/DHA, flavonoids and resveratrol was subjected to pathway
analysis and significance testing for overlap with signals from genome-wide
association studies (GWAS) for common non-communicable diseases and biological
functions. There was an enrichment of genes implicated in immune responses and
disease pathways which was common to all of the treatment conditions tested.
Analysis of biological functions and disease pathways indicated anti-tumorigenic
properties for EPA/DHA. In line with this, significance testing of the
intersection of genes associated with these functional foods and GWAS hits for
common biological functions (ageing and cognition) and non-communicable diseases
(breast cancer, CVD, diabesity, neurodegeneration and psychiatric disorders)
identified significant overlap between the EPA/DHA and breast cancer gene sets.
Dietary intervention with EPA/DHA, flavonoids and resveratrol can target
important biological and disease pathways suggesting a potentially important role
for these bioactive compounds in the prevention and treatment of dietary-related
diseases.
PMID- 29345218
TI - Mitochondrial DNA suggests cryptic speciation in Prodiplosis longifila Gagne
(Diptera: Cecidomyiidae) associated with geographic distance and host
specialization.
AB - Prodiplosis longifila is reported as a pest of a wide range of species cultivated
in America, including citrus, solanaceous species and asparagus. This species has
different behavioural traits that are primarily centred on the oviposition habit
and the feeding of larvae, which can change depending on the host. However,
scarce information is available on population studies and the natural history of
this insect, and uncertainty exists about the taxonomic identity and the
geographic distribution of this species. The main objective was to perform a
phylogenetic and genetic study of P. longifila populations and to define whether
the North American and South American populations belong to the same species or
whether a differentiation process had occurred due to geographic distance. A
second objective was to determine whether this species showed genetic
differentiation by host specialization in South America. The phylogenetic and
population analyses based on DNA barcodes (cytochrome oxidase I gene) and a
region of the ribosomal DNA (ITS2) revealed divergent clades attributable to
geographic distance and host specificity. The North American and South American
P. longifila insects were confirmed to be genetically distinct, and the genetic
distances exceeded the values expected for intraspecific variation. In South
America, the population analysis of P. longifila from tomato, sweet pepper
(Solanaceae), Tahiti lime and key lime (Rutaceae) hosts evidenced high genetic
differentiation between populations associated with different hosts and an
absence of gene flow between these groups, suggesting the corresponding formation
of cryptic species.
PMID- 29345219
TI - Transcriptional changes when Myxococcus xanthus preys on Escherichia coli suggest
myxobacterial predators are constitutively toxic but regulate their feeding.
AB - Predation is a fundamental ecological process, but within most microbial
ecosystems the molecular mechanisms of predation remain poorly understood. We
investigated transcriptome changes associated with the predation of Escherichia
coli by the myxobacterium Myxococcus xanthus using mRNA sequencing. Exposure to
pre-killed prey significantly altered expression of 1319 predator genes. However,
the transcriptional response to living prey was minimal, with only 12 genes being
significantly up-regulated. The genes most induced by prey presence (kdpA and
kdpB, members of the kdp regulon) were confirmed by reverse transcriptase
quantitative PCR to be regulated by osmotic shock in M. xanthus, suggesting
indirect sensing of prey. However, the prey showed extensive transcriptome
changes when co-cultured with predator, with 40 % of its genes (1534) showing
significant changes in expression. Bacteriolytic M. xanthus culture supernatant
and secreted outer membrane vesicles (OMVs) also induced changes in expression of
large numbers of prey genes (598 and 461, respectively). Five metabolic pathways
were significantly enriched in prey genes up-regulated on exposure to OMVs,
supernatant and/or predatory cells, including those for ribosome and
lipopolysaccharide production, suggesting that the prey cell wall and protein
production are primary targets of the predator's attack. Our data suggest a model
of the myxobacterial predatome (genes and proteins associated with predation) in
which the predator constitutively produces secretions which disable its prey
whilst simultaneously generating a signal that prey is present. That signal then
triggers a regulated feeding response in the predator.
PMID- 29345220
TI - Tissue Impression Smears as a Supplementary Diagnostic Method for Histopathology
in Cutaneous Leishmaniasis in Sri Lanka.
AB - Cutaneous leishmaniasis (CL) is diagnosed mainly by light microscopy of smears
made using lesion material. Histopathology is usually done in atypical
presentations or when lesion smears are negative. Tissue impression smears (TIS)
made from skin biopsy specimens were compared with histopathology for the
diagnosis of CL. Out of the 111 patients included, 83 (74.8%) were positive by
either methods. The TIS was positive in 70.3% whereas histopathology was positive
in 56.8% of patients. Tissue impression smears can be used as a supplementary
diagnostic test that gives sensitive and rapid results when tissue biopsies are
used as the source of lesion material for diagnosis of CL.
PMID- 29345221
TI - Therapeutic Response to Dihydroartemisinin-Piperaquine for P. falciparum and P.
vivax Nine Years after Its Introduction in Southern Papua, Indonesia.
AB - Dihydroartemisinin-piperaquine (DHP) has been the first-line treatment of
uncomplicated malaria due to both Plasmodium falciparum and Plasmodium vivax
infections in Papua, Indonesia, since March 2006. The efficacy of DHP was
reassessed to determine whether there had been any decline following almost a
decade of its extensive use. An open-label drug efficacy study of DHP for
uncomplicated P. falciparum and P. vivax malaria was carried out between March
2015 and April 2016 in Timika, Papua, Indonesia. Patients with uncomplicated
malaria were administered supervised DHP tablets once daily for 3 days. Clinical
and laboratory data were collected daily until parasite clearance and then weekly
for 6 weeks. Molecular analysis was undertaken for all patients with recurrent
parasitemia. A total of 129 study patients were enrolled in the study. At day 42,
the polymerase chain reaction-adjusted efficacy was 97.7% (95% confidence
intervals [CI]: 87.4-99.9) in the 61 patients with P. falciparum malaria, and
98.2% [95% CI: 90.3-100] in the 56 patients with P. vivax malaria. By day 2, 98%
(56/57) of patients with P. falciparum and 96.9% (63/65) of those with P. vivax
had cleared their peripheral parasitemia; none of the patients were still
parasitaemic on day 3. Molecular analysis of P. falciparum parasites showed that
none (0/61) had K13 mutations associated previously with artemisinin resistance
or increased copy number of plasmepsin 2-3 (0/61). In the absence of artemisinin
resistance, DHP has retained high efficacy for the treatment of uncomplicated
malaria despite extensive drug pressure over a 9-year period.
PMID- 29345222
TI - Development and implementation of multilocus sequence typing to study the
diversity of the yeast Kluyveromyces marxianus in Italian cheeses.
AB - The yeast Kluyveromyces marxianus possesses advantageous traits like rapid
growth, GRAS (generally regarded as safe) status and thermotolerance that make it
very suitable for diverse biotechnological applications. Although physiological
studies demonstrate wide phenotypic variation within the species, there is only
limited information available on the genetic diversity of K. marxianus. The aim
of this work was to develop a multilocus sequence typing (MLST) method for K.
marxianus to improve strain classification and selection. Analysis of
housekeeping genes in a number of sequenced strains led to the selection of five
genes, IPP1, TFC1, GPH1, GSY2 and SGA1, with sufficient polymorphic sites to
allow MLST analysis. These loci were sequenced in an additional 76 strains and
used to develop the MLST. This revealed wide diversity in the species and
separation of the culture collection and wild strains into multiple distinct
clades. Two subsets of strains that shared sources of origin were subjected to
MLST and split decomposition analysis. The latter revealed evidence of
recombination, indicating that this yeast undergoes mating in the wild. A public
access web-based portal was established to allow expansion of the database and
application of MLST to additional K. marxianus strains. This will aid
understanding of the genetic diversity of the yeast and facilitate
biotechnological exploitation.
PMID- 29345224
TI - Therapy interventions for children with neurodisabilities: a qualitative scoping
study.
AB - BACKGROUND: Therapy interventions emerged four times in the top 10 research
priorities in a James Lind Alliance research prioritisation exercise for children
with neurodisabilities (Morris C, Simkiss D, Busk M, Morris M, Allard A, Denness
J, et al. Setting research priorities to improve the health of children and young
people with neurodisability: a British Academy of Childhood Disability-James Lind
Alliance Research Priority Setting Partnership. BMJ Open 2015;5:e006233). The
National Institute for Health Research (NIHR) commissioned this study as part of
an information-gathering exercise in response to this. OBJECTIVES: The objectives
were to (1) describe the current practice, approaches and schools of thought in
relation to physiotherapy, occupational therapy and speech and language therapy
for children with neurodisability; (2) explore clinical decision-making; (3)
investigate views on outcomes and their measurement, particularly participation
as an outcome, that is, the child's ability to have the opportunity to be
involved in life situations and activities (e.g. communication, mobility,
interpersonal interactions, self-care, learning and applying knowledge); (4) seek
views on the aspects of therapy interventions that have an impact on outcomes;
and (5) elicit stakeholder views on research needs and priorities. DESIGN,
SETTING AND PARTICIPANTS: More than 70 professionals (therapists, service leads,
paediatricians and education staff) and 25 parents participated in a qualitative
interview (either individually or as part of a focus group). RESULTS:
Professional thinking and models of service delivery are in a state of flux and
development. There is a move towards goals-focused, family-centred approaches.
Work tends to be highly individualised, with few protocols. Parents are certain
of the value of therapies, although they may experience difficulties with
provision and may seek (additional) private provision. Therapy interventions are
conceived as three components: the therapist, the procedures/equipment, etc., and
the wider therapeutic environment. They are believed to be highly complex and
poorly understood. Although participation is widely endorsed as a core
intervention objective of therapy interventions, its suitability, or
appropriateness, as an outcome measure was questioned. Other child and/or parent
outcomes were identified as more or equally important. Notions of intermediate
outcomes - in terms of body structure/function, and the achievement of activities
- were regarded as important and not counter to participation-focused approaches.
Among therapists, research on intervention effectiveness was (cautiously)
welcomed. A number of methodological challenges were identified. A portfolio of
study designs - quantitative and qualitative, experimental and observational -
was called for, and which included economic evaluation and clear pathways to
impact. LIMITATIONS: The study was not successful in recruiting children and
young people. Further work is required to elucidate the views of this key
stakeholder group. CONCLUSIONS: Therapy interventions are poorly understood.
There was strong support, tempered a little by concerns among some about the
feasibility of demonstrating impact, for investment in research. FUTURE WORK: The
identification of research priorities was a core study objective, and a wide
ranging research agenda was identified. It included 'foundational' research into
neurodisability, the active components of therapy interventions and the concept
of participation. Three areas of evaluation were identified: overall approaches
to therapy, service organisation and delivery issues, and the evaluation of
specific techniques. Parents regarded evaluations of approaches to therapy (e.g.
goals-focused; supporting family-self management) as priorities, along with
evaluations of models of service provision. Professionals' views were broadly
similar, with an additional emphasis on methodological research. In terms of
specific techniques, there was no shared agreement regarding priorities, with
views informed by personal interests and experiences. FUNDING: The NIHR Health
Technology Assessment programme.
PMID- 29345223
TI - Case Report: Neurobrucellosis with Plastered Spinal Arachnoiditis: A Magnetic
Resonance Imaging-Based Report.
AB - Diffuse spinal arachnoiditis in neurobrucellosis is a rare manifestation. We
report a boy aged 17, presenting with hearing impairment and recurrent vomiting
for 18 months, weight loss for 12 months, dysphagia, dysarthria, hypophonia for 6
months, and gait unsteadiness for 5 months. He had bilateral 5th (motor) to 12th
cranial nerve palsy, wasting and weakness of limbs, fasciculations, absent tendon
reflexes, and positive Babinski's sign. Cerebrospinal fluid (CSF) showed raised
protein and pleocytosis. Magnetic resonance imaging (MRI) showed extensive
enhancing exudates in cisterns and post-contrast enhancement of bilateral 5th,
6th, 7th, and 8th nerves. Spine showed clumping with contrast enhancement of the
cauda equina roots and encasement of the cord with exudates. Serum and CSF were
positive for anti-Brucella antibodies. He showed significant improvement with
antibiotics. At 4 months follow-up, MRI demonstrated near complete resolution of
cranial and spinal arachnoiditis. It is important to recognize such rare atypical
presentations of neurobrucellosis.
PMID- 29345226
TI - Failure to Use Ultrasound Is a Glaring Shortcoming.
PMID- 29345225
TI - Indications for the Surgical Management of Benign Goiter in Adults.
AB - BACKGROUND: Thyroidectomy is still three to six times more common in Germany than
in the USA, Great Britain, and the Scandinavian countries. Thus, the question is
often asked whether thyroidectomy in Germany is being performed for the correct
indications. METHODS: This review is based on studies and guidelines containing
information on the indications for surgery in benign goiter and Graves' disease;
these publications were retrieved by a systematic literature search in the
Medline and Cochrane Library databases (1990-2016). The indications recommended
here were determined by vote by the German Society for General and Visceral
Surgery (Deutsche Gesellschaft fur Allgemein- und Viszeralchirurgie, DGAV).
RESULTS: On the basis of the available evidence (levels 2-4), and in the absence
of prospective studies, the indications for surgery in goiter include a well
founded suspicion of malignancy, local compressive symptoms, and, rarely,
cosmesis. In hyperthyroid goiter and Graves' disease, surgery is a potential
alternative to radio - iodine therapy, particularly if the volume of the thyroid
gland exceeds 80 mL, in patients with advanced or active orbitopathy, and in
female patients who are, or plan to be, pregnant. Large, asymptomatic, euthyroid
nodular goiter without any suspicion of malignancy and scintigraphically "cold"
nodules without any other evidence of malignancy are not indications for surgery.
Thyroid operations of higher levels of difficulty (e.g., recurrent goiter,
retrosternal extension, Graves' disease) should be carried out in institutions
with special expertise in thyroid surgery. CONCLUSION: The decision to operate
should be made on an interdisciplinary basis and in conformity with the relevant
guidelines after all of the appropriate diagnostic studies have been performed.
The radicality of any proposed surgical procedure should be weighed against its
potential complications.
PMID- 29345227
TI - Experience and a Certain Amount of Time Are Required.
PMID- 29345228
TI - Ultrasound First.
PMID- 29345229
TI - Oral Contrast is no Longer Needed.
PMID- 29345230
TI - Critical Scrutiny Needed.
PMID- 29345231
TI - In Reply.
PMID- 29345232
TI - A Rare Cause of Chronic Cough.
PMID- 29345233
TI - Multiple Endobronchial Chondromas.
PMID- 29345235
TI - News on Climate Change, Air Pollution, and Allergic Triggers of Asthma.
AB - The rising frequency of obstructive respiratory diseases during recent years, in
particular allergic asthma, can be partially explained by changes in the
environment, with the increasing presence in the atmosphere of chemical triggers
(particulate matter and gaseous components such as nitrogen dioxide and ozone)
and biologic triggers (aeroallergens). In allergic individuals, aeroallergens
stimulate airway sensitization and thus induce symptoms of bronchial asthma. Over
the last 50 years, the earth's temperature has risen markedly, likely because of
growing concentrations of anthropogenic greenhouse gas. Major atmospheric and
climatic changes, including global warming induced by human activity, have a
considerable impact on the biosphere and on the human environment. Urbanization
and high levels of vehicle emissions induce symptoms of bronchial obstruction (in
particular bronchial asthma), more so in people living in urban areas compared
than in those who live in rural areas. Measures need to be taken to mitigate the
future impact of climate change and global warming. However, while global
emissions continue to rise, we must learn to adapt to climate variability.
PMID- 29345234
TI - Current Approaches to Epistaxis Treatment in Primary and Secondary Care.
AB - BACKGROUND: The lifetime prevalence of epistaxis is approximately 60%, and 6-10%
of the affected persons need medical care. In rare cases, severe bleeding calls
for the rapid initiation of effective treatment. METHODS: This review is based on
pertinent articles that were retrieved by a selective search PubMed, and on the
authors' clinical experience. RESULTS: There are no German guidelines for the
management of epistaxis. The available evidence consists mainly of retro spective
analyses and expert opinions. 65-75% of the patients who require treatment can be
adequately cared for by their primary care physician or by an emergency physician
with baseline measures. If there is persistent anterior epistaxis, an
otorhinolaryngologist can control the bleeding sastisfactorily in 78-88% of cases
with chemical or electrical cauterization. Nasal packing is used if this
treatment fails, or for posterior epistaxis. In a retrospective study, surgical
treatment was found to be more effective than nasal packing in the treatment of
posterior epistaxis (97% versus 62% treatment success). Percutaneous embolization
is an alternative treatment for patients whom general anesthesia would put at
high risk. CONCLUSION: The treatment of severe or recurrent epistaxis requires
the interdisciplinary collaboration of the primary care physician, the emergency
physician, the practice-based otolaryngologist, and the hospital otolaryngology
service. Uniform guidelines and epidemiological studies on this topic would be
desirable.
PMID- 29345237
TI - Beyond the impact factor: may we have your attention, please?
PMID- 29345236
TI - GLCCI1 Polymorphism rs37973 and Response to Treatment of Asthma With Inhaled
Corticosteroids.
AB - BACKGROUND: The response to asthma treatment is highly variable, and having
pharmacogenetic markers that predict response to treatment would bring us one
step closer to personalized treatment. Genome-wide association studies have shown
that polymorphisms in GLCCI1 could be associated with the response to inhaled
corticosteroids (ICSs) in asthma patients. MATERIAL AND METHODS: We genotyped
rs37973 in GLCCI1 in 208 adult asthma patients treated with ICSs. The percentage
change in FEV1, % predicted was analyzed after short-term treatment (3 months)
and long-term treatment (at least 3 years). Treatment was defined as successful
when FEV1 decreased by <30 mL/year. RESULTS: After 3 months of treatment, FEV1, %
predicted was higher in patients with the GG genotype than in patients with the
AG+AA genotype, and this genotype-dependent difference was only evident in
nonsmokers. Similar results were found in nonsmokers and patients with atopy
after at least 3 years of treatment, when all patients were analyzed. Even though
no differences were observed for success of treatment (good vs poor response)
when the whole group of patients was analyzed, genotype-dependent treatment
success was highly influenced by smoking and atopy. The GG genotype was
overrepresented in nonsmokers and patients with atopy and a good response.
CONCLUSIONS: rs37973 was associated with response to short- and long-term
treatment; however, smoking and atopy had a considerable effect on
pharmacogenetic association. Furthermore, in contrast with findings from genome
wide association studies, we found the GG genotype to be associated with better
treatment response.
PMID- 29345238
TI - Assessing coronary disease in patients with severe aortic stenosis: the need for
a 'valid' gold standard for validation studies?
PMID- 29345239
TI - The business of risk.
PMID- 29345240
TI - Polymeric bioresorbable coronary scaffolds: the hype is over, but the dream lives
on.
PMID- 29345242
TI - Joint estimation of activity and attenuation for PET using pragmatic MR-based
prior: application to clinical TOF PET/MR whole-body data for FDG and non-FDG
tracers.
AB - Accurate and robust attenuation correction remains challenging in hybrid PET/MR
particularly for torsos because it is difficult to segment bones, lungs and
internal air in MR images. Additionally, MR suffers from susceptibility artifacts
when a metallic implant is present. Recently, joint estimation (JE) of activity
and attenuation based on PET data, also known as maximum likelihood
reconstruction of activity and attenuation, has gained considerable interest
because of (1) its promise to address the challenges in MR-based attenuation
correction (MRAC), and (2) recent advances in time-of-flight (TOF) technology,
which is known to be the key to the success of JE. In this paper, we implement a
JE algorithm using an MR-based prior and evaluate the algorithm using whole-body
PET/MR patient data, for both FDG and non-FDG tracers, acquired from GE SIGNA
PET/MR scanners with TOF capability. The weight of the MR-based prior is
spatially modulated, based on MR signal strength, to control the balance between
MRAC and JE. Large prior weights are used in strong MR signal regions such as
soft tissue and fat (i.e. MR tissue classification with a high degree of
certainty) and small weights are used in low MR signal regions (i.e. MR tissue
classification with a low degree of certainty). The MR-based prior is pragmatic
in the sense that it is convex and does not require training or population
statistics while exploiting synergies between MRAC and JE. We demonstrate the JE
algorithm has the potential to improve the robustness and accuracy of MRAC by
recovering the attenuation of metallic implants, internal air and some bones and
by better delineating lung boundaries, not only for FDG but also for more
specific non-FDG tracers such as 68Ga-DOTATOC and 18F-Fluoride.
PMID- 29345243
TI - Electronic and mechanical response of graphene on BaTiO3 at martensitic phase
transitions.
AB - Graphene is extremely sensitive to optical, electrical and mechanical stimuli,
which cause a significant variation of the band structure, thus the
physiochemical properties. In our work, we report on changes of strain and doping
in graphene grown by chemical vapor deposition on copper and transferred onto a
BaTiO3(1 0 0) (BTO) single-crystal. The BTO is known as a ferroelectric material,
which undergoes several thermoelastic martensitic phase transitions when it is
cooled from 300 K to 10 K. In order to enhance the very weak Raman signal of the
graphene monolayer (ML) on the BTO, a 15 nm thin gold layer was deposited on top
of the graphene ML to benefit from the surface enhanced Raman scattering. Using
temperature dependent Raman spectral mapping, the principal Raman modes (D, G and
2D) of the graphene ML were followed in situ. From a careful analysis of these
Raman modes, we conclude that the induced strain and doping of the graphene ML
follows the martensitic phase transitions of the BTO crystal. Our study suggests
potential exploitation of the graphene as a highly sensitive opto-mechanical
sensor or transducer.
PMID- 29345244
TI - In vitro physical and biological characterization of biodegradable elastic
polyurethane containing ferulic acid for small-caliber vascular grafts.
AB - Demand for small diameter vascular grafts is growing. The main limitations of
these grafts include induced thrombotic events, lack of in situ
endothelialization, intimal hyperplasia and poor mechanical properties which
impair the graft patency rate in long-term applications. Most anti-thrombotic
modification methods currently in use usually conflict with the formation of an
endothelial cell monolayer on the grafts. Here, we synthesized a novel
biodegradable poly(ether ester urethane)urea elastomer (PEEUU) using
poly(ethylene glycol) and poly(diethylene glycol adipate) as soft segments. To
improve hemocompatibility, synthesized PEEUU was blended with ferulic acid (FA).
Scanning electron microscopy, water contact angle measurement, and tensile
testing were used to characterize the scaffolds. The PEEUU and PEEUU-FA scaffolds
revealed appropriate mechanical properties, with tensile strengths and strains
similar to a coronary artery. In vitro assay demonstrated that the release of FA
from the scaffold is in a sustained manner. Hemocompatibility tests indicated
that the PEEUU-FA sample induced lower platelet adhesion compared to the PEEUU
sample. Reductions in hemolysis and fibrinogen adsorption were detected on the
PEEUU-FA sample. Cell studies showed that PEEUU-FA supported the adhesion,
expansion and proliferation of endothelial cells. The cells maintained an
endothelial cell phenotype through the expression of the endothelial cell marker
CD31. The results revealed that the new PEEUU modified with FA can be considered
as a promising candidate for vascular applications with enhanced blood
compatibility and vascular cell-compatibility.
PMID- 29345245
TI - Isolating long-wavelength fluctuation from structural relaxation in two
dimensional glass: cage-relative displacement.
AB - It has recently been revealed that long-wavelength fluctuation exists in two
dimensional (2D) glassy systems, having the same origin as that given by the
Mermin-Wagner theorem for 2D crystalline solids. In this paper, we discuss how to
characterise quantitatively the long-wavelength fluctuation in a molecular
dynamics simulation of a lightly supercooled liquid. We employ the cage-relative
mean-square displacement (MSD), defined on relative displacement to its cage, to
quantitatively separate the long-wavelength fluctuation from the original MSD.
For increasing system size the amplitude of acoustic long wavelength fluctuations
not only increases but shifts to later times causing a crossover with structural
relaxation of caging particles. We further analyse the dynamic correlation length
using the cage-relative quantities. It grows as the structural relaxation becomes
slower with decreasing temperature, uncovering an overestimation by the four
point correlation function due to the long-wavelength fluctuation. These findings
motivate the usage of cage-relative MSD as a starting point for analysis of 2D
glassy dynamics.
PMID- 29345246
TI - Graphene-based stretchable and transparent moisture barrier.
AB - We propose an alumina-deposited double-layer graphene (2LG) as a transparent,
scalable, and stretchable barrier against moisture; this barrier is indispensable
for foldable or stretchable organic displays and electronics. Both the barrier
property and stretchability were significantly enhanced through the introduction
of 2LG between alumina and a polymeric substrate. 2LG with negligible polymeric
residues was coated on the polymeric substrate via a scalable dry transfer method
in a roll-to-roll manner; an alumina layer was deposited on the graphene via
atomic layer deposition. The effect of the graphene layer on crack generation in
the alumina layer was systematically studied under external strain using an in
situ micro-tensile tester, and correlations between the deformation-induced
defects and water vapor transmission rate were quantitatively analyzed. The
enhanced stretchability of alumina-deposited 2LG originated from the interlayer
sliding between the graphene layers, which resulted in the crack density of the
alumina layer being reduced under external strain.
PMID- 29345247
TI - Calculation of the exposure buildup factors for x-ray photons with continuous
energy spectrum using Monte Carlo code.
AB - Exposure buildup factors are very important for the calculation of radiation
shielding and also applied radiation. We must distinguish the monoenergetic and
continuous energy spectrum gamma source in order to calculate the exposure
buildup factors. In this study, the exposure buildup factors for two x-ray
continuous energy spectra (bremsstrahlung) with 5 and 10 MeV endpoint energies
were calculated up to depths of 10 mfp of water. It was observed that there is a
large difference between the obtained exposure buildup factors due to the
monoenergetic and continuous energy spectrum gamma sources. The calculation
results show that the relative differences in 5 MeV energy for 1 mfp to 10 mfp
are 114% to 44%, respectively, and also the relative differences in 10 MeV energy
for 1 mfp to 10 mfp are 87% to 38%, respectively. Actually, the main purpose of
this paper is to illustrate the fact that there is a significant difference
between the exposure buildup factors due to the continuous and monoenergetic
gamma sources. Therefore, radiation staff must pay more attention to calculating
the thickness of radiation shields for continuous energy gamma sources.
PMID- 29345248
TI - Photo-assisted hysteresis of electronic transport for ZnO nanowire transistors.
AB - Recently, ZnO nanowire field effect transistors (FETs) have received renewed
interest due to their extraordinary low dimensionality and high sensitivity to
external chemical environments and illumination conditions. These prominent
properties have promising potential in nanoscale chemical and photo-sensors. In
this article, we have fabricated ZnO nanowire FETs and have found hysteresis
behavior in their transfer characteristics. The mechanism and dynamics of the
hysteresis phenomena have been investigated in detail by varying the sweeping
rate and range of the gate bias with and without light irradiation.
Significantly, light irradiation is of great importance on charge trapping by
regulating adsorption and desorption of oxygen at the interface of ZnO/SiO2.
Carriers excited by light irradiation can dramatically promote
trapping/detrapping processes. With the assistance of light illumination, we have
demonstrated a photon-assisted nonvolatile memory which employs the ZnO nanowire
FET. The device exhibits reliable programming/erasing operations and a large
on/off ratio. The proposed proto-type memory has thus provided a possible novel
path for creating a memory functionality to other low-dimensional material
systems.
PMID- 29345250
TI - Cancer-associated cachexia.
PMID- 29345249
TI - Effects of 1,25-Dihydroxyvitamin D3 on the Prevention of Chronic Obstructive
Pulmonary Disease (COPD) in Rats Exposed to Air Pollutant Particles Less than 2.5
Micrometers in Diameter (PM2.5).
AB - BACKGROUND This study aimed to investigate the effects of 1,25-dihydroxyvitamin
D3 (1,25(OH)2D3) on airway changes in chronic obstructive pulmonary disease
(COPD) rats exposed to air pollutant particles less than 2.5 micrometers in
diameter (PM2.5), and to evaluate the mechanisms. MATERIAL AND METHODS Three
groups were included in this study: a normal group, a COPD model group, and a
COPD with 1,25(OH)2D3 treatment group. In each group, the rats were divided into
four subgroups: control and different doses of PM2.5 (1.6, 8 and 40 mg/kg body
weight). Apoptosis in lung tissue was detected by terminal deoxynucleotidyl
transferase dUTP nick end labeling (TUNEL). The expression of c-Jun N-terminal
kinase 1 (JNK1) and mucin 5AC (MUC5AC) were detected by real-time polymerase
chain reaction (RT-PCR), Western blotting and immunofluorescence staining.
RESULTS Compared with corresponding subgroups in normal group, the apoptotic
rates in COPD group were significantly increased. By contrast, 1,25(OH)2D3
treatment group significantly reduced COPD-induced apoptosis in lung tissue. Upon
the dose increase of PM2.5, the apoptotic rate was also elevated in each group.
Compared with the corresponding control in each group, PM2.5 increased apoptosis
in a dose-dependent manner. Importantly, 1,25(OH)2D3 also prevented apoptosis in
COPD rats exposed to PM2.5. Mechanically, the expression of MUC5AC and JNK1 in
COPD group was significantly upregulated, compared with corresponding subgroups
in the normal group. Treatment with 1,25(OH)2D3 reduced expression of MUC5AC and
JNK1 in COPD rats. It was found that the expression of MUC5AC and JNK1 was
elevated with the dose increase of PM2.5 in each group. Consistently, 1,25(OH)2D3
also reduced the expression of MUC5AC and JNK1 in COPD rats exposed to PM2.5.
CONCLUSIONS 1,25(OH)2D3 prevented lung injury in COPD rats with or without PM2.5
exposure. Our results suggest that 1,25(OH)2D3 is useful to mitigate the injury
caused by COPD.
PMID- 29345251
TI - Cancer-associated cachexia.
AB - Cancer-associated cachexia is a disorder characterized by loss of body weight
with specific losses of skeletal muscle and adipose tissue. Cachexia is driven by
a variable combination of reduced food intake and metabolic changes, including
elevated energy expenditure, excess catabolism and inflammation. Cachexia is
highly associated with cancers of the pancreas, oesophagus, stomach, lung, liver
and bowel; this group of malignancies is responsible for half of all cancer
deaths worldwide. Cachexia involves diverse mediators derived from the cancer
cells and cells within the tumour microenvironment, including inflammatory and
immune cells. In addition, endocrine, metabolic and central nervous system
perturbations combine with these mediators to elicit catabolic changes in
skeletal and cardiac muscle and adipose tissue. At the tissue level, mechanisms
include activation of inflammation, proteolysis, autophagy and lipolysis.
Cachexia associates with a multitude of morbidities encompassing functional,
metabolic and immune disorders as well as aggravated toxicity and complications
of cancer therapy. Patients experience impaired quality of life, reduced
physical, emotional and social well-being and increased use of healthcare
resources. To date, no effective medical intervention completely reverses
cachexia and there are no approved drug therapies. Adequate nutritional support
remains a mainstay of cachexia therapy, whereas drugs that target overactivation
of catabolic processes, cell injury and inflammation are currently under
investigation.
PMID- 29345253
TI - 3-Acetyl-oleanolic acid ameliorates non-alcoholic fatty liver disease in high fat
diet-treated rats by activating AMPK-related pathways.
AB - 3-Acetyl-oleanolic acid (3Ac-OA) is a derivative of oleanolic acid (OA), which
has shown therapeutic beneficial effects on diabetes and metabolic syndrome. In
this study we investigated whether 3Ac-OA exerted beneficial effect on non
alcoholic fatty liver disease (NAFLD) in rats and its potential underlying
mechanisms. Treatment with 3Ac-OA (1-100 MUmol/L) dose-dependently decreased the
intracellular levels of total cholesterol (TC) and triglyceride (TG) in FFA
treated primary rat hepatocytes and human HepG2 cell lines in vitro. Furthermore,
oil red staining studies showed that 3Ac-OA caused dose-dependent decrease in the
number of lipid droplets in FFA-treated primary rat hepatocytes. SD rats were fed
a high fat diet (HFD) for 6 weeks and subsequently treated with 3Ac-OA (60, 30,
15 mg.kg-1.d-1) for 4 weeks. 3Ac-OA administration significantly decreased the
body weight, liver weight and serum TC, TG, LDL-C levels in HFD rats.
Furthermore, 3AcOA administration ameliorated lipid accumulation and cell
apoptosis in the liver of HFD rats. Using adipokine array analyses, we found that
the levels of 11 adipokines (HGF, ICAM, IGF-1, IGFBP-3, IGFBP-5, IGFBP-6,
lipocalin-2, MCP-1, M-CSF, Pref-1 and RAGE) were increased by more than twofold
in the serum of 3Ac-OA-treated rats, whereas ICAM, IGF-1 and lipocalin-2 had
levels increased by more than 20-fold. Moreover, 3Ac-OA administration
significantly increased the expression of glucose transporter type 2 (GLUT-2) and
low-density lipoprotein receptor (LDLR), as well as the phosphorylation of AMP
activated protein kinase (AMPK), protein kinase B (AKT) and glycogen synthase
kinase 3beta (GSK-3beta) in the liver tissues of HFD rats. In conclusion, this
study demonstrates that 3Ac-OA exerts a protective effect against hyperlipidemia
in NAFLD rats through AMPK-related pathways.
PMID- 29345252
TI - Optimization of lentiviral vector production for scale-up in fixed-bed
bioreactor.
AB - Lentiviral vectors (LVs) are promising tools for gene therapy. However, scaling
up the production methods of LVs in order to produce high-quality vectors for
clinical purposes has proven to be difficult. In this article, we present a
scalable and efficient method to produce LVs with transient transfection of
adherent 293T cells in a fixed-bed bioreactor. The disposable iCELLis bioreactors
are scalable with a large three-dimensional (3D) growth area range between 0.53
and 500 m2, an integrated perfusion system, and a controllable environment for
production. In this study, iCELLis Nano (2.67-4 m2) was used for optimizing
production parameters for scale-up. Transfections were first done using
traditional calcium phosphate method, but in later runs polyethylenimine was
found to be more reliable and easier to use. For scalable LV production,
perfusion rate control by measuring cell metabolite concentrations in the
bioreactor leads to higher productivity and reduced costs. Optimization of cell
seeding density for targeted cell concentration during transfection, use of low
compaction fixed-bed and lowering the culture pH have a positive effect on LV
productivity. These results show for the first time that iCELLis bioreactor is
scalable from bench level to clinical scale LV production.
PMID- 29345254
TI - The mTOR inhibitor AZD8055 overcomes tamoxifen resistance in breast cancer cells
by down-regulating HSPB8.
AB - Tamoxifen, an important endocrine therapeutic agent, is widely used for the
treatment of estrogen receptor positive (ER+) breast cancer. However, de novo or
acquired resistance prevents patients from benefitting from endocrine approaches
and necessitates alternative treatments. In this study, we report that small heat
protein beta-8 (HSPB8) may serve as an important molecule in tamoxifen
resistance. HSPB8 expression is enhanced in MCF-7 cells resistant to tamoxifen
(MCF-7/R) compared to parent cells. Moreover, high expression of HSPB8 associates
with poor prognosis in ER+ breast cancer patients but not in patients without
classification. Stimulating ER signaling by heterogeneous expression of ERa or
17beta-estradiol promotes HSPB8 expression and reduces the cell population in G1
phase. In contrast, blockage of ER signaling by tamoxifen down-regulates the
expression of HSPB8. In addition, knocking down HSPB8 by specific siRNAs induces
significant cell cycle arrest at G1 phase. AZD8055 was found to be more potent
against the proliferation of MCF-7/R cells than that of parent cells, which was
associated with down-regulation of HSPB8. We found that the anti-proliferative
activity of AZD8055 was positively correlated with the HSPB8 expression level in
ER+ breast cancer cells. Thus, AZD8055 was able to overcome tamoxifen resistance
in breast cancer cells, and the expression of HSPB8 may predict the efficacy of
AZD8055 in ER+ breast cancer. This hypothesis deserves further investigation.
PMID- 29345256
TI - Caregiver Perspectives on Communication During Hospitalization at an Academic
Pediatric Institution: A Qualitative Study.
AB - OBJECTIVE: Communication among those involved in a child's care during
hospitalization can mitigate or exacerbate family stress and confusion. As part
of a broader qualitative study, we present an in-depth understanding of
communication issues experienced by families during their child's hospitalization
and during the transition to home. METHODS: Focus groups and individual
interviews stratified by socioeconomic status included caregivers of children
recently discharged from a children's hospital after acute illnesses. An open
ended, semistructured question guide designed by investigators included
communication-related questions addressing information shared with families from
the medical team about discharge, diagnoses, instructions, and care plans. By
using an inductive thematic analysis, 4 investigators coded transcripts and
resolved differences through consensus. RESULTS: A total of 61 caregivers across
11 focus groups and 4 individual interviews participated. Participants were 87%
female and 46% non-white. Analyses resulted in 3 communication-related themes.
The first theme detailed experiences affecting caregiver perceptions of
communication between the inpatient medical team and families. The second
revealed communication challenges related to the teaching hospital environment,
including confusing messages associated with large multidisciplinary teams,
aspects of family-centered rounds, and confusion about medical team member roles.
The third reflected caregivers' perceptions of communication between providers in
and out of the hospital, including types of communication caregivers observed or
believed occurred between medical providers. CONCLUSIONS: Participating
caregivers identified various communication concerns and challenges during their
child's hospitalization and transition home. Caregiver perspectives can inform
strategies to improve experiences, ease challenges inherent to a teaching
hospital, and determine which types of communication are most effective.
PMID- 29345257
TI - Engaging Families as True Partners During Hospitalization.
PMID- 29345255
TI - Pure mechanistic analysis of additive neuroprotective effects between baicalin
and jasminoidin in ischemic stroke mice.
AB - Both baicalin (BA) and jasminoidin (JA) are active ingredients in Chinese herb
medicine Scutellaria baicalensis and Fructus gardeniae, respectively. They have
been shown to exert additive neuroprotective action in ischemic stroke models. In
this study we used transcriptome analysis to explore the pure therapeutic
mechanisms of BA, JA and their combination (BJ) contributing to phenotype
variation and reversal of pathological processes. Mice with middle cerebral
artery obstruction were treated with BA, JA, their combination (BJ), or concha
margaritifera (CM). Cerebral infarct volume was examined to determine the effect
of these compounds on phenotype. Using the hippocampus microarray and ingenuity
pathway analysis (IPA) software, we exacted the differentially expressed genes,
networks, pathways, and functions in positive-phenotype groups (BA, JA and BJ) by
comparing with the negative-phenotype group (CM). In the BA, JA, and BJ groups, a
total of 7, 4, and 11 specific target molecules, 1, 1, and 4 networks, 51, 59,
and 18 canonical pathways and 70, 53, and 64 biological functions, respectively,
were identified. Pure therapeutic mechanisms of BA and JA were mainly overlapped
in specific target molecules, functions and pathways, which were related to the
nervous system, inflammation and immune response. The specific mechanisms of BA
and JA were associated with apoptosis and cancer-related signaling and endocrine
and hormone regulation, respectively. In the BJ group, novel target profiles
distinct from mono-therapies were revealed, including 11 specific target
molecules, 10 functions, and 10 pathways, the majority of which were related to a
virus-mediated immune response. The pure additive effects between BA and JA were
based on enhanced action in virus-mediated immune response. This pure mechanistic
analysis may provide a clearer outline of the target profiles of multi-target
compounds and combination therapies.
PMID- 29345258
TI - Combination of a graphene SERS substrate and magnetic solid phase micro
extraction used for the rapid detection of trace illegal additives.
AB - Surface enhanced Raman scattering (SERS) is an ultra-sensitive spectroscopy
technique, which can provide rich structural information for a great number of
molecules, while solid phase micro-extraction (SPME) is an efficient method for
sample pretreatment in analytical chemistry, particularly in a micro-system. In
the present report, a silver-loaded and graphene-based magnetic composite
(Fe3O4@GO@Ag) was fabricated for use as both a SERS-active substrate and SPME
material. The pi-pi stacking and fluorescence quenching abilities of GO make the
composite a perfect candidate for SERS in analyzing real-world samples.
Therefore, through combining the magnetic nanoparticles with a SPME device, we
have developed a pretreatment method named as disperse magnetic solid phase micro
extraction (Dis-MSPME). In comparison to traditional SPME, the proposed Dis-MSPME
realized solid phase micro-extraction from a dispersive system and largely
improved the extraction efficiency. Furthermore, by combining the advantages of
both Dis-MSPME and SERS we have proposed a new detection method called Dis-MSPME
SERS. Finally, as an example, the illegal additive chloramphenicol (CAP) was
successfully detected in aqueous solution with low LOQ and LOD values (1.0 * 10-8
and 1.0 * 10-10 M, respectively), which was finalized within 10 min based on the
proposed Dis-MSPME-SERS method. Therefore, a simpler, more efficient and
sensitive approach to realize enrichment, magnetic separation and detection, all
in-one, for the detection of illegal additives has been reported, which will be
promising towards the detection of trace amounts of substance in micro-systems.
PMID- 29345259
TI - Polymeric carbon nitride nanomesh as an efficient and durable metal-free catalyst
for oxidative desulfurization.
AB - We report the first use of polymeric carbon nitride (CN) for the catalytic
selective oxidation of H2S. The as-prepared CN with unique ultrathin "nanomeshes"
structure exhibits excellent H2S conversion and high S selectivity. In
particular, the CN nanomesh also displays better durability in the
desulfurization reaction than traditional catalysts, such as carbon- and iron
based materials.
PMID- 29345260
TI - One-pot chemoenzymatic synthesis of trolline and tetrahydroisoquinoline
analogues.
AB - Chemoenzymatic reaction cascades can provide access to chiral compounds from low
cost starting materials in one pot. Here we describe one-pot asymmetric routes to
tetrahydroisoquinoline alkaloids (THIAs) using the Pictet-Spenglerase
norcoclaurine synthase (NCS) followed by a cyclisation, to give alkaloids with
two new heterocyclic rings. These reactions operated with a high atom economy to
generate THIAs in high yields.
PMID- 29345261
TI - An inert 3D emulsification device for individual precipitation and concentration
of amorphous drug nanoparticles.
AB - Nanosizing increases the specific surface of drug particles, leading to faster
dissolution inside the organism and improving the bioavailability of poorly water
soluble drugs. A novel approach for the preparation of drug nanoparticles in
water using chemically inert microfluidic emulsification devices is presented in
this paper. A lithographic fabrication sequence was established, allowing
fabrication of intersecting and coaxial channels of different depths in glass as
is required for 3D flow-focusing. Fenofibrate was used as a model for active
pharmaceutical ingredients with very low water solubility in the experiments. It
was dissolved in ethyl acetate and emulsified in water, as allowed by the 3D flow
focusing geometry. In the thread formation regime, the drug solution turned into
monodisperse droplets of sizes down to below 1 MUm. Fast supersaturation occurs
individually in each droplet, as the disperse phase solvent progressively
diffuses into the surrounding water. Liquid antisolvent precipitation results in
highly monodisperse and amorphous nanoparticles of sizes down to 128 nm which can
be precisely controlled by the continuous and disperse phase pressure. By
comparing optically measured droplet sizes with particle sizes by dynamic light
scattering, we could confirm that exactly one particle forms in every droplet.
Furthermore, a downstream on-chip concentration allowed withdrawal of major
volumes of only the continuous phase fluid which enabled an increase of particle
concentration by up to 250 times.
PMID- 29345262
TI - Copper(i) complexes with phosphine derived from sparfloxacin. Part III:
multifaceted cell death and preliminary study of liposomal formulation of
selected copper(i) complexes.
AB - The cytotoxic effect of iodide or thiocyanate copper(i) complexes (1-PSf, 2-PSf,
3-PSf, 4-PSf) with phosphine derived from sparfloxacin (HSf) and 2,9-dimethyl
1,10-phenanthroline (dmp) or 2,2'-biquinoline (bq) as diimine auxiliary ligands
was proved in vitro on somatic (MRC-5) and neoplastic (MCF7) human cell lines.
Differences in mode of action were investigated in-depth for the selected dmp and
bq complexes (1-PSf, 3-PSf, respectively) by elucidation of the following: (i)
the efficiency to produce reactive oxygen species (ROS) in biological systems
(cyclic voltammetry); (ii) their impact on mitochondrial membrane potential;
(iii) potency for the activation of caspases 3 and 9; (iv) influence on the
degree of DNA degradation (comet assay). It was concluded that the apoptosis of
cancer cells is directly connected to the caspase-dependent mitochondrial pathway
and supported by ROS production along with irreversible DNA fragmentation.
Finally, it was demonstrated that the selected copper(i) complex encapsulated
inside liposomes (1-PSf-L) exhibited enhanced accumulation inside cancer cells.
This resulted in its higher cytotoxicity against cancer cells with therapeutic
index of ca. 60. Increased selective accumulation in active neoplasm with
simultaneous enhanced bioavailability and reduced systemic toxicity of liposomal
formulation of copper(i) complexes can result in the development of new copper
based therapeutics and their successful implementation in anticancer
chemotherapy.
PMID- 29345263
TI - Natural products and ring-closing metathesis: synthesis of sterically congested
olefins.
AB - Covering: 2002 to August 2017.This review highlights recent RCM reactions towards
the synthesis of sterically congested natural products. It offers an insight into
various synthetic targets and approaches and provides information on the
evolution of catalysts as powerful tools enabling the use of increasingly
challenging diene precursors.
PMID- 29345264
TI - Giant spontaneous exchange bias obtained by tuning magnetic compensation in
samarium ferrite single crystals.
AB - Spontaneous exchange bias (SEB) under zero field cooling (ZFC) has recently
attracted lots of attention due to its underlying physics and potential
applications. Here we report the giant SEB (GSEB) of SmFeO3 single crystals by
tuning magnetic compensation by temperature, which is rather convenient. A SEB
field of up to 1 T at 3.9 K after ZFC (-1.4 T at 3.9 K after field cooling) was
obtained. The SEB shows reciprocal relationship with remnant magnetization.
PMID- 29345265
TI - Hierarchical formation of Fe-9eG supramolecular networks via flexible
coordination bonds.
AB - From the interplay between high-resolution scanning tunneling microscopy
imaging/manipulations and density functional theory calculations, we display the
hierarchical formation of supramolecular networks by codeposition of 9eG
molecules and Fe atoms on Au(111) based on the flexible coordination bonds (the
adaptability and versatility in the coordination modes). In the first step,
homochiral islands composed of homochiral G4Fe2 motifs are formed; and then in
the second step, thermal treatment results in the transformation into the porous
networks composed of heterochiral G4Fe2 motifs with the ratio of the components
being constant. In situ STM manipulations and the coexistence of some other
heterochiral G4Fe2 motifs and clusters also show the flexibility of the
coordination bonds involved. These studies may provide a fundamental
understanding of the regulations of multilevel supramolecular structures and shed
light on the formation of designed supramolecular nanostructures.
PMID- 29345266
TI - Efficient interfacial charge transfer through plasmon sensitized Ag@Bi2O3
hierarchical photoanodes for photoelectrocatalytic degradation of chlorinated
phenols.
AB - The present work demonstrates an extremely proficient and robust study of
efficient interfacial charge transfer through plasmonic Ag decorated Bi2O3
hierarchical photoanodes for the photoelectrochemical treatment of chlorinated
phenols. Unique 2D flake-like Bi2O3 hierarchical nanostructures were grown onto a
fluorine-doped tin oxide (FTO) substrate by a simple chemical bath deposition
method using triethanolamine as complexing agent. The formation of Bi2O3 on FTO
was governed by the decomposition of a nucleated bismuth-hydroxyl complex (Bi2O1
x(OH)x) and modification to the electrode was carried out by the deposition of Ag
via a chemical reduction method using hydrazine hydrate. Both the fabricated
electrodes were well characterized for their photo- and electro-optical
properties. Efficient charge separation was observed due to the surface plasmon
resonance phenomenon of silver nanoparticles with the favorable intrinsic
properties of Bi2O3 under application of a small electric bias of 1 V preventing
the recombination of charge carriers and thereby increasing the rate of
photoelectrocatalytic degradation of the chlorinated phenols. PEC degradation
using the Ag@Bi2O3 photoelectrode followed the trend 4-CP < 2,4-DCP < 2,4,6-TCP <
P-CP due to efficient attack at the chlorinated positions by reactive oxygen
species with increasing chlorine substitution and also due to the absence of an
expected chain reaction of the generated chlorine radicals (Cl) during the PEC
reaction. The PEC activity of Ag@Bi2O3 was 1.5 times higher than a Bi2O3
nanoflake electrode for 4-CP over 2 h. The fabricated Ag@Bi2O3 proved to be an
efficient photoelectrode with synergistic solar-induced photoactivity. A detailed
mechanistic study in the presence of scavengers suggests degradation by produced
hydroxyl radical species. Thus, physical insights into the degradation of
chlorinated phenols were obtained.
PMID- 29345267
TI - Ambient storage of microencapsulated Lactobacillus plantarum ST-III by complex
coacervation of type-A gelatin and gum arabic.
AB - Ambient storage of dry powdered probiotics is necessary for manufacturer's cost
reduction and customer's convenience. Complex coacervation is a promising
microencapsulation technique. In this work, a probiotic matrix of type-A
gelatin/gum arabic/sucrose (GE/GA/S) with high coacervation pH was designed,
based on the alkaline isoelectric point of type-A gelatin. Bacterial survival
during ambient storage at room temperature and certain relative humidity were
detected. To clarify the protection factors of the coacervation matrix of
GE/GA/S, dry microcapsules of GA, GE, GE/sucrose and GE/GA were prepared as
controls and compared in terms of their morphology, moisture content, dynamic
vapor absorption and cell viability. Probiotics in GE/GA/S5.5 microcapsules
behaved the best during spray drying, ambient storage and heat treatment. The
results proved that sucrose addition was necessary for cell viability against
environmental stresses, and that encapsulation by complex coacervation was a
positive factor in cell protection, especially at neutral coacervation pH.
PMID- 29345268
TI - Homoleptic U(iii) and U(iv) amidate complexes.
AB - The syntheses of the first homoleptic U(iii) and U(iv) amidate complexes are
described. These can be interconverted by chemical reduction/oxidation, showing
an unusual change in coordination number from four in the U(iii) complex to eight
in the U(iv) complex in the solid state structures.
PMID- 29345269
TI - Tributyltin induces epigenetic changes and decreases the expression of nuclear
respiratory factor-1.
AB - Tributyltin (TBT), a common organotin environmental pollutant, has been widely
used as a component of marine antifouling paints. We previously reported that
exposure to TBT inhibits the expression and DNA binding of nuclear respiratory
factor-1 (NRF-1) and causes neurotoxicity. In the present study, we focused on
the epigenetic effects of TBT and investigated whether TBT decreases NRF-1
expression via epigenetic modifications in SH-SY5Y human neuroblastoma cells.
First, we found that exposure to 300 nM TBT decreases NRF-1 expression. We
examined epigenetic changes induced by TBT, and showed that TBT causes
hypermethylation of the NRF-1 promoter region, increases the amount of methyl-CpG
binding protein 2 (MeCP2) bound to the NRF-1 promoter, and alters the expression
of DNA methyltransferases and ten-eleven translocation (TET) demethylation
enzymes. These results suggest that epigenetic changes play an important role in
regulation of NRF-1 expression. Next, we investigated effect of NRF-1 expression
decrease on cells, and TBT reduces mitochondrial membrane potential and
overexpression of NRF-1 rescued this reduction in membrane potential. Thus, we
suggested that NRF-1 is important for maintaining mitochondrial membrane
potential. Our study indicates that TBT causes epigenetic changes such as
hypermethylation, which increases recruitment of MeCP2 to the NRF-1 promoter and
probably lead to decreased of NRF-1 expression and mitochondrial membrane
potential. Therefore, this research provides new evidence of the epigenetic
action caused by organotin.
PMID- 29345270
TI - Energetics and dynamics of the non-natural fluorescent 4AP:DAP base pair.
AB - The fluorescent non-natural 4-aminophthalimide (4AP) base, when paired to the
complementary 2,4-diaminopyrimidine (DAP) nucleobase, is accommodated in a B-DNA
duplex being efficiently recognized and incorporated by DNA polymerases. To
complement the experimental studies and rationalize the impact of the above non
natural bases on the structure, stability and dynamics of nucleic acid
structures, we performed quantum mechanics (QM) calculations along with classical
molecular dynamics (MD) simulations. QM calculations were initially focused on
the geometry and energetics of the 4AP:DAP non-natural pair and of H-bonded base
pairs between 4AP and all the natural bases in their classical Watson-Crick
geometries. The QM calculations indicate that the 4AP:DAP pair, despite the fact
that it can form 3 H-bonds in a classic Watson-Crick geometry, has a stability
comparable to the A:T pair. Then, we extended the study to reverse Watson-Crick
geometries, characteristic of parallel strands. MD simulations were carried out
on two 13-mer DNA duplexes, featuring a central 4AP:DAP or A:T pair,
respectively. No major structural deformation of the duplex was observed during
the MD simulation. Snapshots from the MD simulations were subjected to QM
calculations to investigate the 4AP:DAP interaction energy when embedded into a
duplex structure, and to investigate the impact of the two non-natural bases on
the stacking interactions with adjacent bases in the DNA duplex. We found a
slight increase in stacking interactions involving the 4AP:DAP pair,
counterbalanced by a moderate decrease in H-bonding interactions of the 4AP:DAP
and of the adjacent base pairs in the duplex. The results of our study are in
agreement with experimental data and complement them by providing an insight into
which factors contribute positively and which factors contribute negatively to
the structural compatibility of the fluorescent 4AP:DAP pair with a B-DNA
structure.
PMID- 29345271
TI - Flocculation on a chip: a novel screening approach to determine floc growth rates
and select flocculating agents.
AB - Flocculation is a key purification step in cell-based processes for the food and
pharmaceutical industry where the removal of cells and cellular debris is aided
by adding flocculating agents. However, finding the best suited flocculating
agent and optimal conditions to achieve rapid and effective flocculation is a non
trivial task. In conventional analytical systems, turbulent mixing creates a
dynamic equilibrium between floc growth and breakage, constraining the
determination of floc formation rates. Furthermore, these systems typically rely
on end-point measurements only. We have successfully developed for the first time
a microfluidic system for the study of flocculation under well controlled
conditions. In our microfluidic device (MUFLOC), floc sizes and growth rates were
monitored in real time using high-speed imaging and computational image analysis.
The on-line and in situ detection allowed quantification of floc sizes and their
growth kinetics. This eliminated the issues of sample handling, sample
dispersion, and end-point measurements. We demonstrated the power of this
approach by quantifying the growth rates of floc formation under forty different
growth conditions by varying industrially relevant flocculating agents (pDADMAC,
PEI, PEG), their concentration and dosage. Growth rates between 12.2 MUm s-1 for
a strongly cationic flocculant (pDADMAC) and 0.6 MUm s-1 for a non-ionic
flocculant (PEG) were observed, demonstrating the potential to rank flocculating
conditions in a quantitative way. We have therefore created a screening tool to
efficiently compare flocculating agents and rapidly find the best flocculating
condition, which will significantly accelerate early bioprocess development.
PMID- 29345272
TI - Preparation of Eu(iii) acetylacetonate-doped well-defined titania particles with
efficient photoluminescence properties.
AB - The aggregation/dispersion of luminescent species is a critical factor that
determines their luminescence properties. In this study, europium(iii)
acetylacetonate (Eu(acac)3) was doped into a titania matrix to form Eu(acac)3
doped titania particles with well-defined size and shape through a microreactor
based sol-gel approach. The morphology and structure of the as-synthesized
products were characterized by Fourier transform infrared spectroscopy, scanning
electron microscopy, transmission electron microscopy, scanning transmission
electron microscopy and X-ray diffraction measurements. The Eu/Ti value of the
products varied in the range from 0.125 to 5.0 and the resulting luminescence
properties were examined. It should be noted that there was an optimum Eu/Ti
value that exhibited the strongest luminescence. A possible reason for this
phenomenon can be explained on the basis of a balance between the inter-molecular
distance of Eu(acac)3 and its doped amount. The effects of the crystal phase of
the titania matrix on luminescence behavior were also investigated. As a result,
Eu(acac)3-doped amorphous titania demonstrated more efficient luminescence than
that after calcined at 550 degrees C for 6 h to convert amorphous to anatase
probably because of the aggregation of Eu species on the crystallite surface. The
stability of the present Eu(acac)3-doped titania was confirmed by preparing thin
films on a glass substrate and by applying UV/ozone treatment. As compared to
bare Eu(acac)3, degradation in luminescence was suppressed in the case of
Eu(acac)3-doped titania. Thus, the present titania-based hybrid with controlled
Eu(acac)3 doping is useful as a stable, luminescent material for optical,
biological and environmental applications.
PMID- 29345283
TI - Regulation of programmed-death ligand in the human head and neck squamous cell
carcinoma microenvironment is mediated through matrix metalloproteinase-mediated
proteolytic cleavage.
AB - Recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is
a devastating malignancy with a poor prognosis. According to recent clinical
studies, tumour growth can be effectively reduced and survival can be improved by
blocking the programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1)
pathway. PD-L1 expression has been proposed as a potential causative mechanism,
as HNSCC is highly immunosuppressive. However, anti-PD-1 treatment is beneficial
only for certain patients. Therefore, the mechanisms controlling PD-L1 expression
warrant further investigation in order to provide a better understanding of the
predicting efficacy of and optimising anti-PD-1 therapy, alone or in combination.
In this study, PD-L1 protein extracted from the cell membrane was found to be
downregulated in OSC-20 cells compared with OSC-19 cells, despite a higher PD-L1
expression in the total cell lysate of the OSC-20 compared with the OSC-19 cells.
Several matrix metalloproteinases (MMPs) were found to be upregulated in HNSCC;
in particular, MMP-7 and -13 were upregulated in the OSC-20 compared with the OSC
19 cells. Purified PD-L1 was degraded by recombinant MMP-13 and -7. The
expression of PD-L1 was significantly restored by a specific inhibitor of MMP-13
(CL82198), which suggested the involvement of MMP-13 in the shedding/cleavage of
PD-L1 in the OSC-20 cells. Among the anticancer drugs conventionally used in the
treatment of patients with HNSCC, paclitaxel increased MMP-13 expression in R/M
HNSCC cells (HOC313 cells) co-cultured without/with dendritic cells (DCs). These
results suggest that the shedding/cleavage of PD-L1 by MMP-13 is one of the
mechanisms behind the protective effect against invasion and metastasis. Thus,
MMP-13 has potential value as a marker predictive of the decreased efficacy of
anti-PD-1 therapy. In addition, paclitaxel is a particularly promising candidate
for combination therapy in R/M HNSCC with anti-PD-1 therapy.
PMID- 29345284
TI - Quantitative proteomics analysis of the role of tetraspanin-8 in the drug
resistance of gastric cancer.
AB - Gastric cancer, due to its high incidence rate, is the second leading cause of
cancer-related mortality worldwide. Chemotherapy is an important component of the
multimodal treatment for gastric cancer; however, a significant impediment to
successful treatment is multidrug resistance (MDR) in patients with gastric
cancer. In the present study, the protein profiles of the MDR cell line,
SGC7901/DDP, and its parental cell line, SGC7901, were comparatively analyzed
through an iTRAQ-based quantitative proteomics technique. The protein tetraspanin
8 (TSPAN8) was found to be highly expressed in the SGC7901/DDP cells. To examine
the role of TSPAN8 in the MDR of SGC7901/DDP cells, we increased cell sensitivity
to drugs by increasing apoptosis. Additionally, the silencing of TSPAN8
downregulated Wnt pathway activity, beta-catenin expression and beta-catenin
transfer to the nucleus. TSPAN8 was found to bind to NOTCH2, facilitating its
mediation of the Wnt/beta-catenin pathway by regulating beta-catenin expression.
Overall, the suppression of TSPAN8 expression may prove to be a promising
strategy which may aid in the development of novel gastric cancer therapeutic
drugs.
PMID- 29345285
TI - The epitranscriptome m6A writer METTL3 promotes chemo- and radioresistance in
pancreatic cancer cells.
AB - N6-methyladenosine (m6A) is the most abundant epitranscriptome modification in
mammalian mRNA. Recent years have seen substantial progress in m6A
epitranscriptomics, indicating its crucial roles in the initiation and
progression of cancer through regulation of RNA stabilities, mRNA splicing,
microRNA processing and mRNA translation. However, by what means m6A is
dynamically regulated or written by enzymatic components represented by
methyltransferase-like 3 (METTL3) and how m6A is significant for each of the
numerous genes remain unclear. We focused on METTL3 in pancreatic cancer, the
prognosis of which is not satisfactory despite the development of
multidisciplinary therapies. We established METTL3-knockdown pancreatic cancer
cell line using short hairpin RNA. Although morphologic and proliferative changes
were unaffected, METTL3-depleted cells showed higher sensitivity to anticancer
reagents such as gemcitabine, 5-fluorouracil, cisplatin and irradiation. Our data
suggest that METTL3 is a potent target for enhancing therapeutic efficacy in
patients with pancreatic cancer. In addition, we performed cDNA expression
analysis followed by gene ontology and protein-protein interaction analysis using
the Database for Annotation, Visualization, and Integrated Discovery and Search
Tool for the Retrieval of Interacting Genes/Proteins databases, respectively. The
results demonstrate that METTL3 was associated with mitogen-activated protein
kinase cascades, ubiquitin-dependent process and RNA splicing and regulation of
cellular process, suggesting functional roles and targets of METTL3.
PMID- 29345286
TI - Cyclooxygenase-2 expression is induced by celecoxib treatment in lung cancer
cells and is transferred to neighbor cells via exosomes.
AB - Lung cancer is one of most common types of cancer worldwide. Lung cancer results
in a death higher rate each year compared to colon, breast and prostate cancer
combined. Celecoxib is a selective inhibitor of cyclooxygenase-2 (COX-2), an
enzyme of which the expression is induced by various stimuli, such as
inflammation. In addition, celecoxib triggers COX-2 loading on exosomes. Exosomes
are small vesicles composed of a lipid bilayer membrane and are found in most
biological fluids, such as blood breast milk and urine. In this study, we focused
on exosomes containing COX-2 proteins from lung cancer cells to determine their
involvement in the interaction with neighbor cells following treatment with
celecoxib. We found that celecoxib induced COX-2 expression in both the cytosol
and exosomes in lung cancer cells. Exosomes from celecoxib-treated lung cancer
cell culture supernatant were isolated and incubated with several types of cells.
The THP-1, monocytic leukemia cell line effectively absorbed COX-2 by lung cancer
cell-derived exosomes. Following incubation with exosomes, the COX-2 protein
level was increased in the THP-1 cells; however, COX-2 mRNA expression was not
affected. Moreover, prostaglandin E2 (PGE2) and vascular endothelial growth
factor (VEGF) production by THP-1 cells was increased following incubation with
exosomes from celecoxib-treated lung cancer cells. Conditioned medium from THP-1
following incubation with exosomes promoted formation in EA.hy926 cells. Taken
together, our findings suggest that celecoxib induces COX-2 expression in lung
cancer cells, and that highly expressed COX-2 in exosomes can be transferred to
other cells.
PMID- 29345287
TI - Intermittent calorie restriction enhances epithelial-mesenchymal transition
through the alteration of energy metabolism in a mouse tumor model.
AB - The effect of intermittent calorie restriction (ICR) on cancer is controversial.
In this study, we examined the effects of ICR and food content in syngeneic
BALB/c mice injected with CT26 mouse colon cancer cells. Mice were subjected to
24-h fasting once a week for 4 weeks, and then provided with a control, high
calorie, or trans fatty acid-rich diet. While ICR resulted in increases in tumor
weights, metastasis and in the number of cancer stem cells (CSCs) in the tumors
or blood of mice fed the control and high-fat diets, it had no effect on body
weight after 4 weeks. In particular, we detected increases in the numbers of CSCs
in the tumor or blood on the day after starvation, when food overconsumption was
detected. Conversely, continuous calorie restriction had no effect on tumor
weight, metastasis, or the number of CSCs in tumors or blood. In the post
starvation period, energy metabolism in the tumor was altered from oxidative
phosphorylation to glycolysis/lactate fermentation, with the acquisition of the
epithelial-mesenchymal transition (EMT) phenotype. Hyperglycemia at the post
starvation period induced the expression of insulin-like growth factor-1, hypoxia
induced factor-1alpha and Nanog, as well as the phosphorylation of Stat3. Taken
together, these findings suggest that ICR induces an increase in the number of
CSCs and enhances EMT by promoting the Warburg/Crabtree effect following post
fasting food overconsumption.
PMID- 29345288
TI - Downregulation of miR-205 is associated with glioblastoma cell migration,
invasion, and the epithelial-mesenchymal transition, by targeting ZEB1 via the
Akt/mTOR signaling pathway.
AB - Glioblastoma (GBM) is the most common type of malignant brain tumor. In spite of
recent advancements in surgical techniques, chemotherapy, and radiation therapy,
patients with GBM often face a dire prognosis. MicroRNAs have been shown to
modulate the aggressiveness of various cancers, and have emerged as possible
therapeutic agents for the management of GBM. miR-205 is dysregulated in glioma
and act as a prognostic indicator. However, the role of miR-205 in the
development of GBM has not been elucidated. To better understand the pathogenesis
of GBM, we examine the biological significance and molecular mechanisms of miR
205 in GBM cells. Zinc finger E-box binding homeobox 1 (ZEB1) has been shown to
regulate the epithelial-mesenchymal transition (EMT), which is strongly
associated with GBM malignancy. In the present study, we show miR-205 expression
is reduced in GBM tissues and cell lines, and ZEB1 expression is inversely
correlated with miR-205 expression. We also show ZEB1 is a downstream target of
miR-205 and the Akt/mTOR signaling pathway is activated when miR-205 interacts
with ZEB1. Increased activity of miR-205 in GBM cells significantly inhibits
migration and invasion, and prevents EMT. Furthermore, overexpression of ZEB1
partially abolishes these inhibitory effects of miR-205. We show that miR-205
negatively regulates the expression of ZEB1 in GBM, inhibits cell migration and
invasion, and prevents EMT, at least in part through the inhibition of the
activation of the Akt/mTOR signaling pathway. Our results indicate miR-205 may be
an efficacious therapeutic agent in the treatment of GBM.
PMID- 29345289
TI - No erythropoietin-induced growth is observed in non-small cell lung cancer cells.
AB - Lung cancer patients have the highest incidence of anemia among patients with
solid tumors. The use of recombinant human erythropoietin (Epo) has consistently
been shown to reduce the need for blood transfusions and to increase hemoglobin
levels in lung cancer patients with chemotherapy-induced anemia. However,
clinical and preclinical studies have prompted concerns that Epo and the presence
of its receptor, EpoR, in tumor cells may be responsible for adverse effects and,
eventually, death. The question has been raised whether Epo promotes tumor growth
and inhibits the death of cancer cells. In this study, we investigated the
presence and functionality of EpoR, as well as the implications of Epo upon the
proliferation and survival of lung cancer cells. Since the protein expression of
both Epo and EpoR is induced by hypoxia, which is frequently present in lung
cancer, the cells were treated with Epo under both normoxic and hypoxic
conditions (1% O2). By using quantitative (real-time) PCR, western blot analysis,
and immunocytochemical staining, three non-small cell lung cancer (NSCLC) cell
lines (A427, A549 and NCI-H358) were analyzed for the expression of EpoR and its
specific downstream signaling pathways [Janus kinase 2 (Jak2)-signal transducer
and activator of transcription 5 (STAT5), phosphatidylinositol-3-kinase (PI3K)
Akt, mitogen-activated protein (MAP) kinase]. The effects of 100 U/ml Epo on cell
proliferation and cisplatin-induced apoptosis were assessed. All NSCLC cell lines
expressed EpoR mRNA and protein, while these levels differed considerably between
the cell lines. We found the constitutive phosphorylation of EpoR and most of its
downstream signaling pathways (STAT5, Akt and ERK1/2) independently of Epo
administration. While Epo markedly enhanced the proliferation and reduced
apoptosis of Epo-dependent UT-7/Epo leukemia cells, it did not affect tumor cell
proliferation or the cisplatin-induced apoptosis of NSCLC cells. Thus, this in
vitro study suggests that there are no tumor-promoting effects of Epo in the
NSCLC cell lines studied, neither under normoxic nor under hypoxic conditions.
PMID- 29345290
TI - Role of nestin expression in angiogenesis and breast cancer progression.
AB - Nestin is an intermediate filament protein and a stem cell marker expressed in
several tumours. There is growing evidence of an association between the
expression level of nestin and the pathogenesis of triple-negative breast cancer
(TNBC). Nestin is also expressed in newly forming tumour vessels and is a
valuable marker of ongoing angiogenesis. In this study, we aimed to evaluate the
prognostic value of nestin expression in breast tumour cells and to determine
whether this expression influences angiogenesis. Immunohistochemical (IHC)
analyses were carried out on 124 cases of invasive ductal carcinoma (IDC) of the
breast with a panel of murine monoclonal antibodies against nestin, CD31, CD34,
SOX-18 and Ki-67. We evaluated nestin expression in tumour and endothelial cells,
Ki-67 in tumour cells, and CD31, CD34 and SOX-18 in endothelial cells. Our
results demonstrated that nestin expression in tumour cells correlated with the
area and number of vessels expressing nestin, CD31, CD34 and SOX-18. We also
found a positive correlation between nestin-expressing vessels and SOX-18
expressing vessels. Our results are consistent with those of previous studies, in
which nestin expression in endothelial cells was shown to be strongly associated
with triple-negative subtype, poorly differentiated G3 tumours, a higher
proliferation index and a shorter overall survival. Nestin expression was also
examined in human breast cancer cell lines (MCF-7, SK-BR-3, MDA-MB-231 and BO2
cells) representing a different level of tumour aggressiveness and reflecting
histological grade. A higher nestin protein level was observed in more aggressive
MDA-MB-231 and BO2 cells than in MCF-7 and SK-BR-3 cells.
PMID- 29345291
TI - MicroRNA-1271 functions as a metastasis and epithelial-mesenchymal transition
inhibitor in human HCC by targeting the PTP4A1/c-Src axis.
AB - MicroRNAs (miRNAs or miRs) have been shown to regulate hepatocellular carcinoma
(HCC) metastasis. In the present study, we focused on the functions of miR-1271
in HCC metastasis. The downregulation of miR-1271 was found to be associated with
to venous infiltration, an advanced TNM stage (III+IV stage) and a shorter
survival time. Our in vitro and in vivo data demonstrated that miR-1271 prevented
HCC cell migration and invasion, as well as the formation of lung metastatic
clusters. In addition, miR-1271 was demonstrated to markedly inhibit the
epithelial-mesenchymal transition (EMT) of HCC cells. Importantly, protein
tyrosine phosphatase type IVA member 1 (PTP4A1) was identified as a direct
downstream target of miR-1271 in HCC. Furthermore, we confirmed that the
phosphorylation of c-Src at Tyr416 mediated by PTP4A1 was a potential anti-HCC
mechanism of action of miR-1271. On the whole, our data indicate that miR-1271
inhibits HCC metastasis by targeting the PTP4A1/c-Src signaling pathway and may
serve as a prospective cancer therapeutic target for HCC.
PMID- 29345292
TI - Preparation and characterization of the antibody recognizing AMACR inside its
catalytic center.
AB - Alpha-methylacyl-CoA racemase (AMACR) catalyzes the beta-oxidation of fatty acids
and is overexpressed in carcinomas in various organs, while its inactivation
results in the inhibition of cancer growth. In the present study, we prepared and
characterized 20 different mouse monoclonal antibodies against human AMACR. In
the course of biopanning of a phage peptide commercial library against in-house
prepared 6H9 and 2A5, and commercial 13H4 antibodies, 10 phage mimotopes
recognized by each type of the antibody were selected. Using the program Pepitope
and the crystal structure of AMACR from Mycobacterium tuberculosis, we reveal for
the first time, at least to the best of our knowledge, that the epitopes
recognizing the antibody against AMACR are composed of conformation sequences
localized inside the AMACR catalytic center. When delivered into live HeLa cells
using cationic lipid-based PULSin reagent, the specific antibodies against AMACR
were co-localized with peroxisomes. The in-house made 6H9 antibody exhibited a
low level of this co-localization compared to the commercially available 63340
antibody, and did not inhibit the growth rate of HeLa and T98G cells. The results
obtained suggest that antibody against AMACR may possess anti-AMACR catalytic
activity and needs to be further investigated as a potential drug for use in
anticancer therapy. On the whole, in this study, we generated several clones of
AMACR antibodies and demonstrated that these antibodies can be colonized into
live cells. Currently, we are testing the growth inhibitory properties of these
antibodies against AMACR.
PMID- 29345293
TI - S100B expression in breast cancer as a predictive marker for cancer metastasis.
AB - In the tumor microenvironment, soluble molecules play important role in the
establishment of a pre-metastatic niche. The S100 calcium-binding protein family
are inflammatory molecules that contribute to the development of a pro
inflammatory tumor microenvironment. S100B belongs to the S100 family and serum
S100B (also known as S100beta) serves as a marker for metastasis in lung cancer,
ovarian cancer and melanoma. However, the association between S100B and the
metastasis of breast cancer is not yet well understood. In the present study, a
relatively low S100B expression was observed in the tumor samples compared to
normal breast tissue among online microarray datasets. When the estrogen receptor
(ER)-negative breast cancer cell lines, MDA-MB-231 and Hs578T, were treated with
recombinant human S100B, cell migration was significantly inhibited and
epithelial cadherin expression was increased. Our results revealed that a high
S100B expression predicted a good overall survival in patients with ER-negative
breast cancer, and good distant metastases-free survival in all patients with
breast cancer via the analysis of the KM plotter and SurvExpress databases.
Although previous studies have indicated that the interaction of S100B with wild
type p53 inhibits p53 function, a high S100B expression is associated with a good
prognosis in patients with p53 mutant and p53 wild-type breast cancers. On the
whole, our findings demonstrate that S100B treatment suppresses the migratory
capacity of ER-negative breast cancer and that S100B expression may serve a
predictive marker for metastasis in breast cancer.
PMID- 29345294
TI - Hypoxia stimulates the cytoplasmic localization of oncogenic long noncoding RNA
LINC00152 in colorectal cancer.
AB - Recent studies have indicated that long noncoding RNAs (lncRNAs) play a pivotal
role in almost all physiological cellular processes, including every stage of
cancer development. Given that hypoxia in the tumor microenvironment is involved
in the malignant behavior of tumors, such as invasion and metastasis, we
investigated the cytoplasmic and nuclear localization of lncRNAs in colorectal
cancer cells. A cell culture under hypoxic conditions revealed several lncRNAs,
such as LINC00152, whose levels were increased in the cytoplasm of colorectal
cancer cells. A database study indicated that LINC00152 shares microRNA-binding
sites, such as miR-138 and miR-193, with the hypoxia-inducible factor 1 (HIF1),
thus suggesting that LINC00152 could possibly function as a competing endogenous
RNA that can augment Hif1 translation in the cytoplasm of hypoxic colorectal
cancer cells. Moreover, the data presented in the studies of surgically resected
samples showed that patients with colorectal cancer exhibiting high LINC00152
expression were associated with a worsened survival rate; this supports the
suggested oncogenic function of LINC00152 in the cytoplasm under hypoxic
conditions. The present study demonstrated that lncRNA networks could provide
diagnostic tools and novel therapeutic targets against colorectal cancer cells.
PMID- 29345295
TI - Upregulation of the BDNF/TrKB pathway promotes epithelial-mesenchymal transition,
as well as the migration and invasion of cervical cancer.
AB - Brain-derived neurotrophic factor (BDNF) has previously been demonstrated to be
associated with several types of cancer. In addition, its receptor, tropomyosin
related kinase B (TrkB) is involved in tumor invasion and metastasis. Epithelial
mesenchymal transition (EMT) is associated with metastasis in cancers. Thus, The
aim of the present study was to examine whether BDNF/TrKB expression is linked to
a poor survival and the acquisition of the EMT phenotype in cervical cancer. We
found that a high positive expression of BDNF/TrKB was associated with poor
survival in cervical cancer. Our results revealed that high expression levels of
BDNF/TrKB were observed in cervical cancer compared to normal cells. Importantly,
we demonstrated that the silencing of TrKB suppressed the activation of EMT via
the downregulation of N-cadherin, vimentin, matrix metalloproteinase (MMP)2 and
MMP9, and the upregulation of E-cadherin and tissue inhibitor of
metalloproteinases (TIMP)2, which resulted in suppressed cell proliferation,
migration and invasion. Furthermore, high phosphorylation levels of ERK and Akt
were observed in the cervical cancer cells, while these levels were decreased in
the cells in which TrKB was knocked down. On the whole, these findings suggest
that the BDNF/TrKB pathway is a promising target for the prevention of tumor
proliferation, invasion, metastasis and EMT in cervical cancer cells.
PMID- 29345297
TI - miR-135b-5p promotes gastric cancer progression by targeting CMTM3.
AB - CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) is considered to be a
tumor suppressor gene in multiple types of malignancies. Previous studies have
indicated that CMTM3 suppresses metastasis and epithelial-mesenchymal transition
(EMT) in gastric cancer. However, its role in gastric cancer cell proliferation
has rarely been discussed. Moreover, the regulatory mechanisms of CMTM3 in
gastric cancer remain unclear. In this study, RT-qPCR and IHC were used to assess
the expression of CMTM3 and miR-135b-5p in gastric cancer tissues and cell lines.
We found that the expression of miR-135b-5p was negatively associated with CMTM3
in gastric cancer tissues, and we verified that miR-135b-5p directly targeted
CMTM3 in gastric cancer cells by dual-luciferase reporter assay. CCK8 assay,
Transwell assay and flow cytometric analysis were conducted to examine the
functions of CMTM3 and miR-135b-5p in vitro. Our results demonstrated that the
overexpression of CMTM3 or the suppression of miR-135b-5p using an inhibitor
suppressed SGC-7901 gastric cancer cell proliferation, invasion and cell cycle
progression, and promoted SGC-7901 cell apoptosis. Furthermore, a BALB/c nude
mouse subcutaneous xenograft model was used to verify the function of miR-135b-5p
and CMTM3. Our results revealed that miR-135b-5p inhibitor significantly
suppressed SGC-7901 cell tumorigenesis in vivo. In addition, IHC revealed that
CMTM3 expression was markedly increased in tumors infected with miR-135b-5p
inhibitor lentivirus. On the whole, the findings of the present study suggest
that the overexpression of miR-135b-5p inhibits CMTM3 expression, and promotes
gastric cancer progression and metastasis. Our findings provide a novel
therapeutic target for gastric cancer.
PMID- 29345298
TI - Leishmania amazonensis isolated from human visceral leishmaniasis:
histopathological analysis and parasitological burden in different inbred mice.
AB - Leishmania amazonensis is a major etiological agent of human cutaneous
leishmaniasis in the Americas; nevertheless there are some reports of this
species causing visceral disease in dogs and men. In the present work we have
studied a Leishmania strain isolated from a human case of visceral leishmaniasis.
We have infected different mouse strains and analyzed the development of the
disease, studying the parasite's ability to visceralize and whether this ability
is influenced by host genetics. Female BALB/c, C57BL/6, C57BL/10, CBA, DBA/2, and
C3H/He mice were subcutaneously infected with 104 L. amazonensis amastigotes.
BALB/c, C57BL/6 and C57BL/10 mice were found to be very susceptible to infection,
showing lesions that developed to necrosis and ulceration. CBA mice developed a
late but severe lesion. DBA/2 mice developed only discrete lesions, while C3H/He
mice did not develop any lesions. All mouse strains except C3H/He showed some
degree of visceralization, presenting parasites in the spleen, while BALB/c,
C57BL/6 and CBA presented parasites also in the liver. Moreover, most of the
strains presented high parasite load at the infection site, whereas DBA and
C3H/He mice showed low or no parasite load 90 days after infection, respectively.
Histopathology corroborates the results, showing that susceptible mice presented
an inflammatory reaction with parasites in the skin, lymph nodes and spleen,
while strains that are more resistant presented low parasitism and discrete
inflammatory reaction. Results indicate that this isolate is extremely virulent,
can easily visceralize and that the pathogenesis of leishmaniasis is, at least in
part, related to the genetic background of the host.
PMID- 29345299
TI - The continuing misuse of null hypothesis significance testing in biological
anthropology.
AB - There is over 60 years of discussion in the statistical literature concerning the
misuse and limitations of null hypothesis significance tests (NHST). Based on the
prevalence of NHST in biological anthropology research, it appears that the
discipline generally is unaware of these concerns. The p values used in NHST
usually are interpreted incorrectly. A p value indicates the probability of the
data given the null hypothesis. It should not be interpreted as the probability
that the null hypothesis is true or as evidence for or against any specific
alternative to the null hypothesis. P values are a function of both the sample
size and the effect size, and therefore do not indicate whether the effect
observed in the study is important, large, or small. P values have poor
replicability in repeated experiments. The distribution of p values is continuous
and varies from 0 to 1.0. The use of a cut-off, generally p <= 0.05, to separate
significant from nonsignificant results, is an arbitrary dichotomization of
continuous variation. In 2016, the American Statistical Association issued a
statement of principles regarding the misinterpretation of NHST, the first time
it has done so regarding a specific statistical procedure in its 180-year
history. Effect sizes and confidence intervals, which can be calculated for any
data used to calculate p values, provide more and better information about tested
hypotheses than p values and NHST.
PMID- 29345296
TI - Vitamin D derivatives potentiate the anticancer and anti-angiogenic activity of
tyrosine kinase inhibitors in combination with cytostatic drugs in an A549 non
small cell lung cancer model.
AB - Numerous in vitro and in vivo studies have demonstrated that calcitriol
[1,25(OH)2D3] and different vitamin D analogs possess antineoplastic activity,
regulating proliferation, differentiation and apoptosis, as well as angiogenesis.
Vitamin D compounds have been shown to exert synergistic effects when used in
combination with different agents used in anticancer therapies in different
cancer models. The aim of this study was to evaluate the mechanisms of the
cooperation of the vitamin D compounds [1,24(OH)2D3 (PRI-2191) and 1,25(OH)2D3]
with tyrosine kinase inhibitors (imatinib and sunitinib) together with
cytostatics (cisplatin and docetaxel) in an A549 non-small cell lung cancer
model. The cytotoxic effects of the test compounds used in different combinations
were evaluated on A549 lung cancer cells, as well as on human lung microvascular
endothelial cells (HLMECs). The effects of such combinations on the cell cycle
and cell death were also determined. In addition, changes in the expression of
proteins involved in cell cycle regulation, angiogenesis and the action of
vitamin D were analyzed. Moreover, the effects of 1,24(OH)2D3 on the anticancer
activity of sunitinib and sunitinib in combination with docetaxel were examined
in an A549 lung cancer model in vivo. Experiments aiming at evaluating the
cytotoxicity of the combinations of the test agents revealed that imatinib and
sunitinib together with cisplatin or docetaxel exerted potent anti-proliferative
effects in vitro on A549 lung cancer cells and in HLMECs; however, 1,24(OH)2D3
and 1,25(OH)2D3 enhanced the cytotoxic effects only in the endothelial cells.
Among the test agents, sunitinib and cisplatin decreased the secretion of
vascular endothelial growth factor (VEGF)-A from the A549 lung cancer cells. The
decrease in the VEGF-A level following incubation with cisplatin correlated with
a higher p53 protein expression, while no such correlation was observed following
treatment of the A549 cells with sunitinib. Sunitinib together with docetaxel and
1,24(OH)2D3 exhibited a more potent anticancer activity in the A549 lung cancer
model compared to double combinations and to treatment with the compounds alone.
The observed anticancer activity may be the result of the influence of the test
agents on the process of tumor angiogenesis, for example, through the
downregulation of VEGF-A expression in tumor and also on the induction of cell
death inside the tumor.
PMID- 29345300
TI - Angiosarcoma following treatment of basal cell carcinoma: a report of two cases.
PMID- 29345301
TI - Diphenylcyclopropenone-induced psoriatic koebnerization.
PMID- 29345302
TI - Body mass prediction from femoral volume and sixteen other femoral variables in
the elderly: BMI and adipose tissue effects.
AB - OBJECTIVES: The frequently used prediction equations of body mass do not seem
appropriate for elderly individuals. Here, we establish the relationship between
femoral dimensions and known body mass in elderly individuals in order to develop
prediction formulas and identify the factors affecting their accuracy. MATERIALS
AND METHODS: The body mass linear least-squares regression is based on 17 femoral
dimensions, including femoral volume, and 66 individuals. Body proportion and
composition effects on accuracy are analyzed by means of the body mass index
(BMI) and on a subset sample (n = 25), by means of the masses of adipose, bone
and muscle tissues. RESULTS: Most variables significantly reflect body mass.
Among them, six dimensions (e.g., biepicondylar breadth, femoral volume, and head
femoral diameter) present percent standard errors of estimate ranging from 9.5 to
11% (r = 0.72-0.81) in normal BMI samples. Correlations are clearly lower in
samples with normal and abnormal BMI [r = 0.38-0.58; % of standard error of
estimate (SEE) = 17.3-19.6%] and not significantly correlated in females (femoral
volume) who present high proportions of abnormal BMI and adipose tissue. In the
subset, femoral volume is well correlated with bone mass (r = 0.88; %SEE = 7.9%)
and lean body mass (r = 0.67; %SEE = 17.2%). DISCUSSION: Our body mass estimation
equations for elderly individuals are relevant since relatively low correlations
are recurrent in studies using younger individuals of known body mass. However,
age, sex, lifestyle, and skeleton considerations of studied populations can
provide information about the relevance of the body mass estimation, which is
dependent on the BMI classification and the proportion of adipose tissue. Our
general considerations can be used for studies of younger individuals.
PMID- 29345303
TI - Divided nevus of the penis.
PMID- 29345304
TI - Toward more robust plant-soil feedback research.
AB - Understanding if and how plant-soil biota feedbacks (PSFs) shape plant
communities has become a major research priority. In this paper, we draw on a
recent, high-profile PSF study to illustrate that certain widely used
experimental methods cannot reliably determine if PSFs occur. One problem
involves gathering soil samples adjacent to multiple conditioning plants, mixing
the samples and then growing phytometers in the mixtures to test for PSFs. This
mixed soil approach does not establish that the conditioning plant being present
caused the soil biota to be present, the first step of a PSF. Also, soil mixing
approximates replacing raw data with averages prior to analysis, a move certain
to generate falsely precise statistical estimates. False precision also results
from sample sizes being artificially inflated when phytometers are misinterpreted
as experimental units. Plant biomass ratios become another source of false
precision when individual plant values contribute to multiple ratio observations.
Any one of these common missteps can cause still living null hypotheses to be
pronounced dead, and risks of this increase with numbers of missteps. If soil
organisms truly structure plant communities, then null hypotheses indicating
otherwise will not survive proper testing. We discuss conceptual, experimental
and analytical refinements to facilitate accurate testing.
PMID- 29345305
TI - Detection of mitochondrial haplogroups in a small avar-slavic population from the
eigth-ninth century AD.
AB - OBJECTIVES: In the sixth century AD, Avars came to Central Europe from middle
Eurasian steppes and founded a strong Empire called the Avar Khagante (568
799/803 AD) in the Pannonian basin. During the existence of this empire, they
undertook many military and pugnacious campaigns. In the seventh century, they
conquered the northern territory inhabited by Slavs, who were further recruited
in Avar military and were commissioned with obtaining food supplies. During
almost 200 years of Avar domination, a significant influence by the Avar culture
(especially on the burial rite) and assimilation with indigenous population
(occurrence of "East Asian"cranial features) could be noticed in this mixed area,
which is supported by achaeological and anthropologcal research. Therefore we
expected higher incidence of east Eurasian haplogroups (introduced by Avars) than
the frequencies detected in present-day central European populations. MATERIALS
AND METHODS: Mitochondrial DNA from 62 human skeletal remains excavated from the
Avar-Slavic burial site Cifer-Pac (Slovakia) dated to the eighth and ninth
century was analyzed by the sequencing of hypervariable region I and selected
parts of coding region. Obtained haplotypes were compared with other present-day
and historical populations and genetic distances were calculated using standard
statistical method. RESULTS AND DISCUSSION: In total, the detection of
mitochondrial haplogroups was possible in 46 individuals. Our results prooved a
higher frequency of east Eurasian haplogroups in our analyzed population (6.52%)
than in present-day central European populations. However, it is almost three
times lower than the frequency of east Eurasian haplogroups detected in other
medieval Avar populations. The statistical analysis showed a greater similarity
and the lowest genetic distances between the Avar-Slavic burial site Cifer-Pac
and medieval European populations than the South Siberian, East and Central Asian
populations. CONCLUSION: Our results indicate that the transfer of Avar genetic
variation through their mtDNA was rather weak in the analyzed mixed population.
PMID- 29345306
TI - Hypoalbuminaemia segregates different prognostic subgroups within the refined
standard risk acute graft-versus-host disease score.
AB - Hypoalbuminaemia has been previously described to predict worse non-relapse
mortality (NRM) and inferior overall survival (OS) in allogeneic haematopoietic
cell transplant (allo-HCT) recipients. Here, we evaluate the role of
hypoalbuminaemia (<35 g/l) at time of onset of acute graft-versus-host disease
(aGVHD) when incorporated into the refined aGVHD score. The study population
consisted of 522 patients, median age 53 (18-75) years, who underwent an allo-HCT
mostly for haematological malignancies. Standard risk (SR) aGVHD comprised 467
patients (89%) and the number of high risk (HR) cases was 55 (11%). Median follow
up for all surviving patients was 26 (3-55) months. Two-year OS was significantly
better in patients with SR aGVHD with a serum albumin >=35 g/l compared to SR
with albumin <35 g/l [70% (95% CI = 64-76%) vs. 49% (95% CI = 42-56%), P <
0.0001]. Also, patients with SR aGVHD and a serum albumin level of >=35 g/l had a
significantly lower NRM at 1-year post-transplantation [6% (95% CI = 3-10%) vs.
25% (95% CI = 20-32%), P < 0.0001]. After our findings are validated in a large
cohort of patients, we propose that hypoalbuminaemia should be incorporated into
the refined aGVHD risk score to further its ability to predict outcomes within
this group.
PMID- 29345307
TI - Competitive ability, stress tolerance and plant interactions along stress
gradients.
AB - Exceptions to the generality of the stress-gradient hypothesis (SGH) may be
reconciled by considering species-specific traits and stress tolerance
strategies. Studies have tested stress tolerance and competitive ability in
mediating interaction outcomes, but few have incorporated this to predict how
species interactions shift between competition and facilitation along stress
gradients. We used field surveys, salt tolerance and competition experiments to
develop a predictive model interspecific interaction shifts across salinity
stress gradients. Field survey and greenhouse tolerance tests revealed tradeoffs
between stress tolerance and competitive ability. Modeling showed that along
salinity gradients, (1) plant interactions shifted from competition to
facilitation at high salinities within the physiological limits of salt
intolerant plants, (2) facilitation collapsed when salinity stress exceeded the
physiological tolerance of salt-intolerant plants, and (3) neighbor removal
experiments overestimate interspecific facilitation by including intraspecific
effects. A community-level field experiment, suggested that (1) species
interactions are competitive in benign and, facilitative in harsh condition, but
fuzzy under medium environmental stress due to niche differences of species and
weak stress amelioration, and (2) the SGH works on strong but not weak stress
gradients, so SGH confusion arises when it is applied across questionable stress
gradients. Our study clarifies how species interactions vary along stress
gradients. Moving forward, focusing on SGH applications rather than exceptions on
weak or nonexistent gradients would be most productive.
PMID- 29345308
TI - Positive size-speed relationships in gametes and vegetative cells of
Chlamydomonas reinhardtii; implications for the evolution of sperm.
AB - It is commonly held that differences in gametes of the two sexes (anisogamy)
evolved from ancestors whose gametes were similar in size and behavior (isogamy).
Underlying many hypotheses explaining anisogamy are assumed relationships between
cell size and speed in the ancestral isogamous population. Using the isogamous
alga Chlamydomonas reinhardtii, we explored size-speed distributions in
vegetative and gamete cells of 10 cell lines, and clonal data from within two
cell lines. We applied an independent speed selection approach to gamete
populations of C. reinhardtii, monitoring correlated responses in size following
selection for high speed. We demonstrate positive size-speed relationships in
clones, cell lines, and artificially selected speed selection lines. We found
different size-speed relationships in the two cell types of C. reinhardtii even
though they overlap in size, suggesting that cell composition and/or programs of
gene expression are capable of altering this relationship, and that the
relationship is evolvable. The positive genetic size-speed correlation means that
the division of parent vegetative cells into numerous gametes trades off against
not only size, but also speed, a trade-off that has not received previous
attention. Our results support reevaluating the role of speed selection in the
evolution of anisogamy.
PMID- 29345309
TI - Microbial mitigation-exacerbation continuum: a novel framework for microbiome
effects on hosts in the face of stress.
AB - A key challenge to understanding microbiomes and their role in ecological
processes is contextualizing their effects on host organisms, particularly when
faced with environmental stress. One influential theory, the Stress Gradient
Hypothesis, might predict that the frequency of positive interactions increases
with stressful conditions such that microbial taxa would mitigate harmful effects
on host performance. Yet, equally plausible is that microbial taxa could
exacerbate these effects. Here, we introduce the Mitigation-Exacerbation
Continuum as a novel framework to conceptualize microbial mediation of stress. We
(1) use this continuum to quantify microbial mediation of stress for six plant
species and (2) test the association between these continuum values and natural
species' abundance. We factorially manipulated a common stress (allelopathy) and
the presence of soil microbes to quantify microbial effects in benign and
stressed environments for two critical early life-history metrics, seed
germination and seedling biomass. Although we found evidence of both mitigation
and exacerbation among the six species, exacerbation was more common. Across
species, the degree of microbial-mediated effects on germination explained >80%
of the variation of natural field abundances. Our results suggest a critical role
of soil microbes in mediating plant stress responses, and a potential microbial
mechanism underlying species abundance.
PMID- 29345310
TI - A potential role of knockout serum replacement as a porcine follicular fluid
substitute for in vitro maturation: Lipid metabolism approach.
AB - The use of supplements, such as porcine follicular fluid (pFF), fetal bovine
serum and human serum albumin are widely used during in vitro maturation (IVM) in
different species but these supplements contain undefined components that cause
technical difficulties in standardization and influence the efficiency of IVM.
Knockout serum replacement (KSR) is a synthetic protein source, without any
undefined growth factors or differentiation-promoting factors. Therefore, it is
feasible to use KSR as a defined component for avoiding effects of unknown
molecules in an IVM system. In this study, the rates of oocyte maturation and
blastocyst formation after parthenogenetic activation (PA), somatic cell nuclear
transfer (SCNT) and in vitro fertilization (IVF) were significantly higher in the
5% KSR supplemented group than in the unsupplemented control group and more
similar to those of the 10% pFF supplemented group. Moreover, the intensity of
GDF9, BMP15, ROS, GSH, BODIPY-LD, BODIPY-FA, and BODIPY-ATP staining showed
similar values between 5% KSR and 10% pFF, which have significant difference with
control group. Most of the gene expression related to lipid metabolism with both
supplements exhibited similar patterns. In conclusion, 5% KSR upregulated lipid
metabolism and thereby provides an essential energy source to sustain and improve
oocyte quality and subsequent embryo development after PA, SCNT, and IVF. These
indications support the idea that KSR used as a defined serum supplement for
oocyte IVM might be universally used in other species.
PMID- 29345311
TI - Calcium-sensing receptor activates the NLRP3 inflammasome in LS14 preadipocytes
mediated by ERK1/2 signaling.
AB - The study of the mechanisms that trigger inflammation in adipose tissue is key to
understanding and preventing the cardiometabolic consequences of obesity. We have
proposed a model where activation of the G protein-coupled calcium sensing
receptor (CaSR) leads to inflammation and dysfunction in adipose cells. Upon
activation, CaSR can mediate the expression and secretion of proinflammatory
factors in human preadipocytes, adipocytes, and adipose tissue explants. One
possible pathway involved in CaSR-induced inflammation is the activation of the
NLR family, pyrin domain-containing 3 (NLRP3) inflammasome, that promotes
maturation and secretion of interleukin (IL)-1beta. The present work aimed to
study whether CaSR mediates the activation of NLRP3 inflammasome in the human
adipose cell model LS14. We assessed NLRP3 inflammasome priming and assembly
after cinacalcet-induced CaSR activation and evaluated if this activation is
mediated by downstream ERK1/2 signaling in LS14 preadipocytes. Exposure to 2 MUM
cinacalcet elevated mRNA expression of NLRP3, CASP-1, and IL-1beta, as well as an
increase in pro-IL-1beta protein. In addition, CaSR activation triggered NLRP3
inflammasome assembly, as evidenced by a 25% increase in caspase-1 activity and
63% IL-1beta secretion. CaSR silencing (siRNA) abolished the effect. Upstream ERK
pathway inhibition decreased cinacalcet-dependent activation of NLRP3
inflammasome. We propose CaSR-dependent NLRP3 inflammasome activation in
preadipocytes through ERK signaling as a novel mechanism for the development of
adipose dysfunction, that may favor the cardiovascular and metabolic consequences
of obesity. To the best of our knowledge, this is the first report linking the
inflammatory effect of CaSR to NLRP3 inflammasome induction in adipose cells.
PMID- 29345312
TI - Phylogenetic patterns of trait and trait plasticity evolution: Insights from
amphibian embryos.
AB - Environmental variation favors the evolution of phenotypic plasticity. For many
species, we understand the costs and benefits of different phenotypes, but we
lack a broad understanding of how plastic traits evolve across large clades.
Using identical experiments conducted across North America, we examined prey
responses to predator cues. We quantified five life-history traits and the
magnitude of their plasticity for 23 amphibian species/populations (spanning
three families and five genera) when exposed to no cues, crushed-egg cues, and
predatory crayfish cues. Embryonic responses varied considerably among species
and phylogenetic signal was common among the traits, whereas phylogenetic signal
was rare for trait plasticities. Among trait-evolution models, the Ornstein
Uhlenbeck (OU) model provided the best fit or was essentially tied with Brownian
motion. Using the best fitting model, evolutionary rates for plasticities were
higher than traits for three life-history traits and lower for two. These data
suggest that the evolution of life-history traits in amphibian embryos is more
constrained by a species' position in the phylogeny than is the evolution of life
history plasticities. The fact that an OU model of trait evolution was often a
good fit to patterns of trait variation may indicate adaptive optima for traits
and their plasticities.
PMID- 29345313
TI - A microfluidic chip with a staircase pH gradient generator, a packed column and a
fraction collector for chromatofocusing of proteins.
AB - A microfluidic device for pH gradient chromatofocusing is presented, which
performs creation of a micro-column, pH gradient generation, and fraction
collection in a single device. Using a sieve micro-valve, anion exchange
particles were packed into a microchannel in order to realize a solid-phase
absorption column. To fractionate proteins according to their isoelectric points,
elution buffer solutions with a stepwise pH gradient were prepared in 16 parallel
mixing reactors and flowed through the micro-column, wherein a protein mixture
was previously loaded. The volume of the column is only 20 nL, hence it allows
extremely low sample consumption and fast analysis compared with a conventional
system. We demonstrated separation of two proteins, albumin-fluorescein
isothiocyanate conjugate (FITC-BSA) and R-Phycoerythrin (R-PE), by using a
microcolumn of commercial charged polymeric particles (Source 15Q). The
microfluidic device can be used as a rapid diagnostic tool to analyse crude
mixtures of proteins or nucleic acids and determine adsorption/desorption
characteristics of various biochemical products, which can be helpful for
scientific fundamental understanding as well as instrumental in various
industrial applications, especially in early stage screening and process
development.
PMID- 29345314
TI - The prevalence and distribution of sheep scab in Wales: a farmer questionnaire
survey.
AB - Outbreaks of ovine psoroptic mange in the U.K. have increased 100-fold since its
deregulation in 1992, with the highest prevalence in Wales, a region of high
sheep density. A cross-sectional, retrospective, questionnaire-based survey of
7500 members of the association of Welsh lamb and beef farmers [Welsh Lamb and
Beef Producers Ltd (WLBP)] was used to investigate the prevalence and
distribution of sheep scab in this region in 2015. The survey was completed by
14.0% (n = 972) of potential respondents. Scab outbreaks were reported on 15.8%
(n = 154) of farms in 2015. However, 29.0% (n = 282) of farms reported at least
one scab outbreak and 2.4% (n = 23) of farms had experienced between six and 10
outbreaks in the previous 10 years. Most outbreaks occurred during September
January (83.0%, n = 150), and were clustered around Brecon (mid-Wales) and Bangor
(North Wales). Farmers who used common grazing were significantly more likely to
report scab outbreaks in the previous 10 years than farmers who did not. No
quarantine procedures for sheep bought in were used by 29.0% (n = 262) of
farmers. Future research should be directed towards the development of localized
management programmes, with a particular focus on areas of common grazing.
PMID- 29345315
TI - Chlorophyll fluorescence induction and relaxation system for the continuous
monitoring of photosynthetic capacity in photobioreactors.
AB - The development of high-performance photobioreactors equipped with automatic
systems for non-invasive real-time monitoring of cultivation conditions and
photosynthetic parameters is a challenge in algae biotechnology. Therefore, we
developed a chlorophyll (Chl) fluorescence measuring system for the online
recording of the light-induced fluorescence rise and the dark relaxation of the
flash-induced fluorescence yield (Qa- - re-oxidation kinetics) in
photobioreactors. This system provides automatic measurements in a broad range of
Chl concentrations at high frequency of gas-tight sampling, and advanced data
analysis. The performance of this new technique was tested on the green
microalgae Chlamydomonas reinhardtii subjected to a sulfur deficiency stress and
to long-term dark anaerobic conditions. More than thousand fluorescence kinetic
curves were recorded and analyzed during aerobic and anaerobic stages of
incubation. Lifetime and amplitude values of kinetic components were determined,
and their dynamics plotted on heatmaps. Out of these data, stress-sensitive
kinetic parameters were specified. This implemented apparatus can therefore be
useful for the continuous real-time monitoring of algal photosynthesis in
photobioreactors.
PMID- 29345316
TI - Histopathological findings in pregnancy associated cutaneous hyperpigmentation.
AB - Hyperpigmentation in pregnancy is a common phenomenon, experienced to some degree
by up to 90% of pregnant women. It mainly involves sun-exposed areas, but it can
extend to non-exposed zones. Cases with extensive hyperpigmentation are rarely
reported. In this paper, we describe the case of a 30-year-old phototype V woman
in her 37th week of pregnancy, who presented with brownish hyperpigmentation of
the skin in extensive areas, including both axillae, the abdomen and the lowest
part of the back. In the abdomen, there was a reinforcement of the
hyperpigmentation through the linea nigra and the umbilicus. The
hyperpigmentation affected the buttocks as well and involved the intertriginous
area between them. Histopathologic analysis showed a hyperpigmented basal layer
of the epidermis with no melanocytic atypia or melanocytic nests. Histochemical
staining for iron did not show any deposits. Immunohistochemical studies for HMB
45, Melan A and SOX10 demonstrated an increased number of melanocytes. There was
hyperpigmentation of basal layer keratinocytes. We also performed
immunohistochemical stains for estrogen and progesterone receptors, which were
both negative. The patient was examined 3 months after delivery, evidencing a
significant clearing of the lesions.
PMID- 29345317
TI - An orientation-independent DIC microscope allows high resolution imaging of
epithelial cell migration and wound healing in a cnidarian model.
AB - Epithelial cell dynamics can be difficult to study in intact animals or tissues.
Here we use the medusa form of the hydrozoan Clytia hemisphaerica, which is
covered with a monolayer of epithelial cells, to test the efficacy of an
orientation-independent differential interference contrast microscope for in vivo
imaging of wound healing. Orientation-independent differential interference
contrast provides an unprecedented resolution phase image of epithelial cells
closing a wound in a live, nontransgenic animal model. In particular, the
orientation-independent differential interference contrast microscope equipped
with a 40x/0.75NA objective lens and using the illumination light with wavelength
546 nm demonstrated a resolution of 460 nm. The repair of individual cells, the
adhesion of cells to close a gap, and the concomitant contraction of these cells
during closure is clearly visualized.
PMID- 29345318
TI - Retrospective study on midfacial advancement in syndromic craniosynostosis: case
series.
AB - AIMS: The aim of this study was to evaluate elastic distraction surgical
procedures performed on patients with syndromic craniosynostosis using
cephalometric analyses. METHODS: Eleven patients who underwent surgical midfacial
advancement were divided into three groups: G1 - monobloc frontofacial; G2 - Le
Fort III; and G3 - high-level Le Fort I. The cephalometric analyses were manually
created through cephalometric radiographs of each patient: T1 - preoperative; T2
6 months postoperatively; and T3 - 12 months postoperatively. The cephalometric
landmark points were A and O. The distances between preoperative and
postoperative tracings were measured. RESULTS: Point A advanced with no
significant relapse 12 months after surgery. Point O advanced with a significant
relapse rate of 28.5% postoperatively (p = 0.019). The vertical movement of
points A and O increased by 40.6% (p = 0.033) and 38.8% (p = 0.032),
respectively. There were no significant statistical differences between the
assessed surgical techniques and syndromes with regard to midfacial advancement.
CONCLUSION: Point O has presented statistically significant relapse only in
horizontal movement after 12 months. The cephalometric analysis performed in the
present study only suggested no differences between the studied surgical
techniques and syndromes with regard to midfacial advancement in syndromic
craniosynostosis.
PMID- 29345320
TI - Dental local anesthesia for patients with pseudocholinesterase deficiency.
PMID- 29345319
TI - Endothelial cells enhance adipose mesenchymal stromal cell-mediated matrix
contraction via ALK receptors and reduced follistatin: Potential role of
endothelial cells in skin fibrosis.
AB - Abnormal cutaneous wound healing can lead to formation of fibrotic hypertrophic
scars. Although several clinical risk factors have been described, the cross-talk
between different cell types resulting in hypertrophic scar formation is still
poorly understood. The aim of this in vitro study was to investigate whether
endothelial cells (EC) may play a role in skin fibrosis, for example,
hypertrophic scar formation after full-thickness skin trauma. Using a
collagen/elastin matrix, we developed an in vitro fibrosis model to study the
interaction between EC and dermal fibroblasts or adipose tissue-derived
mesenchymal stromal cells (ASC). Tissue equivalents containing dermal fibroblasts
and EC displayed a normal phenotype. In contrast, tissue equivalents containing
ASC and EC displayed a fibrotic phenotype indicated by contraction of the matrix,
higher gene expression of ACTA2, COL1A, COL3A, and less secretion of follistatin.
The contraction was in part mediated via the TGF-beta pathway, as both inhibition
of the ALK4/5/7 receptors and the addition of recombinant follistatin resulted in
decreased matrix contraction (75 +/- 11% and 24 +/- 8%, respectively). In
conclusion, our study shows that EC may play a critical role in fibrotic events,
as seen in hypertrophic scars, by stimulating ASC-mediated matrix contraction via
regulation of fibrosis-related proteins.
PMID- 29345321
TI - Good Practices for Observational Studies of Maternal Weight and Weight Gain in
Pregnancy.
PMID- 29345322
TI - Effect of substrate stiffness on hepatocyte migration and cellular Young's
modulus.
AB - Hepatic fibrosis progress accompanied by an unbalanced extracellular matrix (ECM)
degradation and deposition leads to an increased tissue stiffness. Hepatocytes
interplay with all intrahepatic cell populations inside the liver. However, how
hepatocytes migration and cellular Young's modulus influenced by the substrate
stiffness are not well understood. Here, we established a stiffness-controllable
in vitro cell culture model by using a polyvinyl alcohol (PVA) hydrogel that
mimicked the same physical stiffness as a fibrotic liver. Three levels of
stiffness were used in our experiment that corresponded to the stiffness levels
found in normal liver tissue (4.5 kPa), the early (19 kPa) and late stages (37
kPa) of fibrotic liver tissues. Cytoskeleton of hepatocyte was influenced by
substrate stiffness. Soft substrate promoted the cellular migration and
directionality. The cellular Young's modulus firstly increased and then decreased
with increasing substrate stiffness. Integrin-beta1 and beta-catenin expression
on cytomembrane were up-regulated and down-regulated with the increase of
substrate stiffness, respectively. Our data not only suggested that hepatocytes
were sensitive to substrate stiffness, but also suggested that there may be a
potential relationship among substrate stiffness, cellular Young's modulus and
the dynamic balance of integrin-beta1 and beta-catenin pathways. These results
may provide us a new insight in mechanism investigation of mechano-dependent
diseases, especially like fibrosis related diseases.
PMID- 29345323
TI - Vernalization can regulate flowering time through microRNA mechanism in Brassica
rapa.
AB - Vernalization is an important process that regulates the floral transition in
plants. MicroRNAs (miRNAs) are endogenous non-coding small RNA (sRNA) molecules
that function in plant growth and development. Despite that miRNAs related to
flowering have previously been characterized, their roles in response to
vernalization in pak-choi (Brassica rapa ssp. chinensis) has never been studied.
Here, two sRNA libraries from B. rapa leaves (vernalized and non-vernalized
plants) were constructed and sequenced. Two hundred eight known and 535 novel
miRNAs were obtained, of which 20 known and 66 new miRNAs were significantly
differentially expressed and considered as vernalization-related miRNAs. The
corresponding targets were predicted on the basic of sequence homology search. In
addition, 11 miRNAs and eight targets were selected for real-time quantitative
PCR to confirm their expression profiles. Functional annotation of targets using
gene ontology and Kyoto encyclopedia of genes and genomes results suggested that
most targets were significantly enriched in the hormone signaling pathway.
Moreover, a decreased indole-3-acetic acid (IAA) and an increased GA3 hormone
were detected after vernalization, indicating that the IAA and GA3 might response
to vernalization. These results indicated that vernalization regulates flowering
through microRNA mechanism by affecting endogenous hormone level in B. rapa. This
study provides useful insights of promising miRNAs candidates involved in
vernalization in B. rapa, and facilitates further investigation of the miRNA
mediated molecular mechanisms of vernalization in B. rapa.
PMID- 29345324
TI - Autocrine signals increase ovine mesenchymal stem cells migration through
Aquaporin-1 and CXCR4 overexpression.
AB - Sheep is a relevant large animal model that is frequently used to test innovative
tissue engineering (TE) approaches especially for bone reconstruction.
Mesenchymal stem cells (MSCs) are used in TE applications because they represent
key component of adult tissue repair. Importantly, MSCs from different species
show similar characteristics, which facilitated their application in
translational studies using animal models. Nowadays, many researches are focusing
on the use of ovine mesenchymal stem cells (oMSCs) in orthopedic preclinical
settings for regenerative medicine purposes. Therefore, there is a need to
amplify our knowledge on the mechanisms underlying the behaviour of these cells.
Recently, several studies have shown that MSC function is largely dependent on
factors that MSCs release in the environment, as well as, in conditioned medium
(CM). It has been demonstrated that MSCs through autocrine and paracrine signals
are able to stimulate proliferation, migration, and differentiation of different
type of cells including themselves. In this study, we investigated the effects of
the CM produced by oMSCs on oMSCs themselves and we explored the signal pathways
involved. We observed that CM caused an enhancement of oMSC migration.
Furthermore, we found that CM increased levels of two membrane proteins involved
in cell migration, Aquaporin 1 (AQP1), and C-X-C chemokine receptor type 4
(CXCR4), and activated Akt and Erk intracellular signal pathways. In conclusion,
taken together our results suggest the high potential of autologous CM as a
promising tool to modulate behaviour of MSCs thus improving their use in
therapeutically approaches.
PMID- 29345325
TI - A new retrograde transillumination technique for videolaryngoscopic tracheal
intubation.
AB - This single-centre, prospective trial was designed to assess the efficacy of a
new retrograde transillumination device called the 'Infrared Red Intubation
System' (IRRIS) to aid videolaryngoscopic tracheal intubation. We included 40
adult patients, who were undergoing elective urological surgery under general
anaesthesia. We assessed the ability to differentiate the transilluminated
glottis from other structures and found a median (IQR [range]) larynx recognition
time of 8 (5-14 [3-28]) s. The difference in laryngeal visibility on the screen
between the deactivated vs. activated device expressed on a visual analogue scale
was significant (6 (4-7 [2-10]) vs. 10 (8-10 [4-10]); p < 0.001). The number of
laryngoscope insertions was 1 (1-2 [1-3]) and the device showed high values on a
visual analogue scale ranging from 0 (lowest score) to 10 (highest score) for
helpfulness (6 (5-7 [2-10])), credibility (10 (8-10 [5-10])) and ease of use (10
(9-10 [8-10])). Tracheal intubation with the system lasted 26 (16-32 [6-89]) s.
No alternative technique of securing the airway was necessary. The lowest SpO2
during intubation was 98 (97-99 [91-100])%. We conclude that this method of
retrograde transillumination can assist videolaryngoscopy.
PMID- 29345326
TI - Live-Animal Imaging of Renal Function by Multiphoton Microscopy.
AB - Intravital microscopy, microscopy of living animals, is a powerful research
technique that combines the resolution and sensitivity found in microscopic
studies of cultured cells with the relevance and systemic influences of cells in
the context of the intact animal. The power of intravital microscopy has recently
been extended with the development of multiphoton fluorescence microscopy systems
capable of collecting optical sections from deep within the kidney at subcellular
resolution, supporting high-resolution characterizations of the structure and
function of glomeruli, tubules, and vasculature in the living kidney. Fluorescent
probes are administered to an anesthetized, surgically prepared animal, followed
by image acquisition for up to 3 hr. Images are transferred via a high-speed
network to specialized computer systems for digital image analysis. This general
approach can be used with different combinations of fluorescent probes to
evaluate processes such as glomerular permeability, proximal tubule endocytosis,
microvascular flow, vascular permeability, mitochondrial function, and cellular
apoptosis/necrosis. (c) 2018 by John Wiley & Sons, Inc.
PMID- 29345327
TI - Basics of Digital Microscopy.
AB - Modern digital microscopy combines the equipment of classical light microscopy
with a computerized imaging system. The technique comprises image formation by
optics, image registration by a camera, and saving of image data in a computer
file. This chapter describes limitations that are particular to each of these
processes, including optical resolution, efficiency of image registration,
characteristics of image file formats, and data management. Further suggestions
are given which serve, in turn, to help construct a set of guidelines aimed at
optimization of digital microscopic imaging. (c) 2018 by John Wiley & Sons, Inc.
PMID- 29345328
TI - Lasers for Flow Cytometry: Current and Future Trends.
AB - Lasers are the principal light sources for flow cytometers. Virtually all
cytometers are equipped with at least one (and often many more) lasers. This unit
covers the various types of lasers available and the qualities that make them
suitable or unsuitable for use in flow cytometers. Also included is a discussion
of future directions, particularly in the area of tunable laser development.
Practical tips are provided for building multilaser cytometer systems. (c) 2018
by John Wiley & Sons, Inc.
PMID- 29345329
TI - Generating Quantitative Cell Identity Labels with Marker Enrichment Modeling
(MEM).
AB - Multiplexed single-cell experimental techniques like mass cytometry measure 40 or
more features and enable deep characterization of well-known and novel cell
populations. However, traditional data analysis techniques rely extensively on
human experts or prior knowledge, and novel machine learning algorithms may
generate unexpected population groupings. Marker enrichment modeling (MEM)
creates quantitative identity labels based on features enriched in a population
relative to a reference. While developed for cell type analysis, MEM labels can
be generated for a wide range of multidimensional data types, and MEM works
effectively with output from expert analysis and diverse machine learning
algorithms. MEM is implemented as an R package and includes three steps: (1)
calculation of MEM values that quantify each feature's relative enrichment in the
population, (2) reporting of MEM labels as a heatmap or as a text label, and (3)
quantification of MEM label similarity between populations. The protocols here
show MEM analysis using datasets from immunology and oncology. These MEM
implementations provide a way to characterize population identity and novelty in
the context of computational and expert analyses. (c) 2018 by John Wiley & Sons,
Inc.
PMID- 29345332
TI - Environmental electron microscopy: materials in their real live in gas or liquid.
PMID- 29345330
TI - Non-Parametric Comparison of Single Parameter Histograms.
AB - A number of methods have been developed to compare single parameter histograms.
Some perform a channel-by-channel analysis and others give a single statistic
about how the histograms may or may not differ. If they do differ, then the
significance of the difference or confidence limit is usually provided. The
specific location(s) for the greatest deviations may also be given. Some are more
effective at resolving severely overlapping populations and others work poorly
when there is any significant overlap. Each method makes certain assumptions
about the data. It is important to understand the assumptions being made and to
understand the limitations of each method. It is essential to know how to
identify when a comparison method will work for a given set of histograms. This
unit explores the different methods, and provides a guide for the reader to
choose the most appropriate method(s) to use for a specific data set(s). (c) 2018
by John Wiley & Sons, Inc.
PMID- 29345333
TI - Effects and mechanism of puerarin on the human retinoblastoma cells.
AB - Puerarin is an isoflavonoid that is extracted from Kudzu root and is considered
to have an anti-tumor effect. In the present study, the effects of puerarin on
human retinoblastoma (RB) cells and the related pathways was determined. The
retinoblastoma RB cell lines were used in this study. Cell viability and colony
formation capacity were measured by MTT and colony formation assays. Cell cycle
was determined by flow cytometry. Cell migration and invasion were examined by
Transwell assay. The expression of cell cycle, EMT, and MAPK/ERK signal pathway
related proteins were detected by western blot following puerarin treatment. The
results revealed that cell viability and proliferation of RB cells treated with
puerarin were significantly lower in RB cells compared to the control group.
Puerarin significantly decreased the proportion of cells during S phase which was
accompanied with increase in cells at G0/1 and G2 phases. Moreover, puerarin
suppressed cell migration, invasion and up-regulated E-Cadherin expression as
well as down-regulated Vimentin and alpha-SMA expression. Furthermore, puerarin
treatment suppressed the expression of p-MEK and p-ERK in RB cells. Our findings
suggest that puerarin contributes to in the treatment of RB and other malignant
tumors.
PMID- 29345334
TI - Roles of the three Mycobacterium smegmatis katG genes for peroxide detoxification
and isoniazid susceptibility.
AB - Three different katG sequences (katGI, katGII and katGIII) were identified in the
Mycobacterium smegmatis genome. The contributions of the three katG genes to
survival of the bacterium were examined by constructing disruptants of these
three genes. The katGIII sequence did not produce a functional catalase
peroxidase. Analyses of peroxidase activity and mRNA expression revealed that in
wild type M. smegmatis, expression dominance between KatGI and KatGII was
switched in the exponential and stationary growth phases. Susceptibility of the
M. smegmatis gene disruptants to hydrogen peroxide (H2 O2 ) was tested in two
growth phases. In the exponential phase, the katGI-null strain was more
susceptible to H2 O2 than the katGII-null strain, indicating that KatGI plays a
more important role in survival than KatGII in this growth phase. In contrast, in
the stationary phase, growth of the katGII-null strain was inhibited at lower
concentrations of H2 O2 . These results suggest that M. smegmatis has two types
of catalase-peroxidases, expressions of which are controlled under different gene
regulatory systems. Isoniazid (INH) susceptibilities of the katG-null strains
were also examined and it was found that katGI is a major determinant of M.
smegmatis susceptibility to INH.
PMID- 29345335
TI - Heat shock protein 70 modulates neural progenitor cells dynamics in human
neuroblastoma SH-SY5Y cells exposed to high glucose content.
AB - In the current experiment, detrimental effects of high glucose condition were
investigated on human neuroblastoma cells. Human neuroblastoma cell line SH-SY5Y
were exposed to 5, 40, and 70 mM glucose over a period of 72 h. Survival rate and
the proliferation of cells were analyzed by MTT and BrdU incorporation assays.
Apoptosis was studied by the assays of flow cytometry and PCR array. In order to
investigate the trans-differentiation capacity of the cell into mature neurons,
we used immunofluorescence imaging to follow NeuN protein level. The
transcription level of HSP70 was shown by real-time PCR analysis. MMP-2 and -9
activities were shown by gelatin Zymography. According to data from MTT and BrdU
incorporation assay, 70 mM glucose reduced cell viability and proliferation rate
as compared to control (5 mM glucose) and cells treated with 40 mM glucose (P <
0.05). Cell exposure to 70 mM glucose had potential to induced apoptosis after 72
h (P < 0.05). Our results also demonstrated the sensitivity of SH-SY5Y cells to
detrimental effects of high glucose condition during trans-differentiation into
mature neuron-like cells. Real-time PCR analysis confirmed the expression of
HSP70 in cells under high content glucose levels, demonstrating the possible cell
compensatory response to an insulting condition (pcontrol vs 70 mM group <0.05).
Both MMP-2 and -9 activities were reduced in cells being exposed to 70 mM
glucose. High glucose condition could abrogate the dynamics of neural progenitor
cells. The intracellular level of HSP70 was proportional to cell damage in high
glucose condition.
PMID- 29345336
TI - gammadelta cells and tumor microenvironment: A helpful or a dangerous liason?
AB - gammadelta T cells are a subset of T lymphocytes that have been implicated in
immunosurveillance against infections and tumors. gammadelta T cells are endowed
with antitumor activities, and hence several gammadelta T cell-based small-scale
clinical trials have been conducted either by in vivo activation by intravenous
administration of aminobiphosphonates or by adoptive transfer of in vitro
expanded gammadelta T cells. Although both these strategies have yielded
promising results, there are a number of limitations associated with each of them
which, if overcome may help to further improve efficacy. One of the most
important limits is the possible polarization of tumor-infiltrating gammadelta T
cells toward different gammadelta T cells population with functional activities
that help the progression and spread of the tumor. Here, we review the modalities
and the possible mechanisms involved in the polarization of tumor-infiltrating
gammadelta T cells upon interaction with several components of the tumor
microenvironment and discuss their implications for the manipulation of
gammadelta T cells in cancer immunotherapy.
PMID- 29345337
TI - Effects of Benzoapyrene on migration and invasion of lung cancer cells
functioning by TNF-alpha.
AB - In this study, we attempted to find out the underlying mechanism of Benzoapyrene
and metastasis of lung cancer cells. We also did experiments to testify the
connection between BaP and its potential target, TNF-alpha. Cell median lethal
dose (IC50 ) of both cells was measured by crystal violet method. Quantitative
real-time reverse transcription PCR (qRT-PCR) and Western blot were employed to
detect the expression of TNF-alpha. Wound healing assay and transwell assay were
utilized to testify the impacts of BaP and TNF-alpha on the metastasis of lung
cancer cells. Cell death rate was elevated with the increase of BaP
concentration. BaP increased the number of metastatic cells of lung cancer. The
expressions of TNF-alpha pathway-associated protein (TNF-alpha, NF-kB [P65],
Caspase3, and Caspase8) were enhanced by overexpressed BaP. TNF-alpha shRNA
suppressed the positive effects of BaP on migration and invasion of lung cancer
cells. Our study validated the positive effects of BaP on the metastasis of lung
cancer cells. We also revealed the instrumental role of TNF-alpha in helping the
development of lung cancer cells induced by BaP.
PMID- 29345338
TI - MIAT lncRNA is overexpressed in breast cancer and its inhibition triggers
senescence and G1 arrest in MCF7 cell line.
AB - Long non-coding RNAs are known as key regulators in the progression and
metastasis of breast cancer. MIAT originally has been considered as an lncRNA to
be associated with a susceptibility to myocardial infarction. Here, we have
detected the expression of MIAT in different cancer cells and a series of breast
tumor tissue. MIAT expression was much higher in high-grade tumors compared to
low-grade ones. Unlike P53 positive tumors, MIAT expression was upregulated in
ER, PR, Her2 positive tumor tissues. Knockdown MIAT suppressed breast cancer cell
proliferation and caused G1 arrest in cell cycle. Furthermore, downregulation of
MIAT promoted apoptosis and significantly decreased migration of breast cancer
cells. An increase in the expression of mir-302, mir-150, and a decrease in the
expression of mir-29c were detected following MIAT silencing. More importantly,
knockdown MIAT significantly elevated the expression of p16Ink4A and Cox2, which
commitment cellular senescence in breast cancer cells. Altogether, our results
suggest that MIAT involved in breast cancer progression and could be candidate as
a novel tumor marker for diagnosis and treatment of breast cancer.
PMID- 29345339
TI - The role of Cdk5-mediated Drp1 phosphorylation in Abeta1-42 induced mitochondrial
fission and neuronal apoptosis.
AB - Alzheimer's disease, one of the most common neurodegenerative diseases, is
pathologically characterized by Amyloid beta containing plaques and
neurofibrillary tangles. Amyloid beta (Abeta) induces neuronal apoptosis through
the intracellular Ca2+ increase, subsequent hyperactivation of cyclin-dependent
kinase 5 (Cdk5) and mitochondrial abnormality. Recently, Cdk5 was identified as
an upstream regulator of mitochondrial fission during neuronal apoptosis, but the
underlying mechanism remains unclear. Here, in vitro phosphorylation assays
showed that Cdk5 could phosphorylate the recombinant Drp1 at Serine 579. Abeta1
42 stimulation increased the phosphorylation level of Drp1 at Serine 579 in mouse
cortical neurons. Cdk5 inhibitor roscovitine and knockdown of Cdk5 by a
lentiviral vector expressing shRNA targeting Cdk5 (Lenti-Cdk5-shRNA) efficiently
prevented Abeta1-42 induced Drp1 phosphorylation in neurons. In addition, Abeta1
42 stimulation induced markedly mitochondrial fission in neurons. Roscovitine,
Lenti-Cdk5-shRNA and expression of phospho-defect mutatant GFP-Drp1-S579A in
neurons attenuated Abeta1-42 induced mitochondrial fission, whereas expression of
phospho-mimetic mutant GFP-Drp1-S579D alone resulted in mitochondiral fission
similar to Abeta1-42 stimulation. Moreover, Roscovitine and Lenti-Cdk5-shRNA
suppressed the cleavage of caspase-3 and protected neurons against Abeta1-42
induced neuronal apoptosis.Thus, our data indicate that Drp1 is a direct target
of Cdk5, and Cdk5-mediated phosphorylation of Drp1 at Serine 579 regulates Abeta1
42 induced mitochondrial fission and neuronal toxicity.
PMID- 29345340
TI - Berberine demonstrates anti-inflammatory properties in Helicobacter pylori
infected mice with chronic gastritis by attenuating the Th17 response triggered
by the B cell-activating factor.
AB - Berberine (BBR) is an isoquinoline alkaloid derived from various medicinal herbs.
Previous studies have suggested that BBR exerts antimicrobial, antitumor, and
antidiabetic effects and can be used to treat Helicobacter pylori-induced chronic
gastritis. However, the exact mechanism by which BBR inhibits H. pylori infection
is not fully understood. We investigated the anti-inflammatory properties and
potential mechanism of BBR in H. pylori-infected mice with chronic gastritis. We
found that BBR can suppress the expression of pro-inflammatory genes IL-6, TGF
beta, and IL-1beta and upregulate anti-inflammatory gene IL-10 expression in the
mucosa and RAW 264.7 macrophages. Exposure to BBR also reduced the expression and
accumulation of IL-17 in the mucosa and CD4+ T cells activated by anti-CD3 and
anti-CD28, and it decreased the frequency of IL-17-producing CD4+ T cells. B cell
activating factor (BAFF) production was inhibited by BBR and by cultured
dendritic and CD4+ T cells. Furthermore, we demonstrated that BAFF can trigger
the Th17 response by promoting the production of pro-Th17 cytokines IL-6, TGF
beta, and IL-1beta, which are strongly associated with the anti-inflammatory role
of BBR in chronic gastritis caused by H. pylori. In conclusion, we determined
that BBR has anti-inflammatory effects on H. pylori-induced chronic gastritis by
attenuating the BAFF-triggered Th17 response.
PMID- 29345341
TI - Novel insights into FAS defects underlying autoimmune lymphoproliferative
syndrome revealed by studies in consanguineous patients.
AB - Autoimmune lymphoproliferative syndrome (ALPS) is a primary immunodeficiency
disease due to impaired Fas-Fas ligand apoptotic pathway. It is characterized by
chronic nonmalignant, noninfectious lymphadenopathy and/or splenomegaly
associated with autoimmune manifestations primarily directed against blood cells.
Herein, we review the heterogeneous ALPS molecular bases and discuss recent
findings revealed by the study of consanguineous patients. Indeed, this peculiar
genetic background favored the identification of a novel form of AR ALPS-FAS
associated with normal or residual protein expression, expanding the spectrum of
ALPS types. In addition, rare mutational mechanisms underlying the splicing
defects of FAS exon 6 have been identified in AR ALPS-FAS with lack of protein
expression. These findings will help decipher critical regions required for the
tight regulation of FAS exon 6 splicing. We also discuss the genotype-phenotype
correlation and disease severity in AR ALPS-FAS. Altogether, the study of ALPS
molecular bases in endogamous populations helps to better classify the disease
subgroups and to unravel the Fas pathway functioning.
PMID- 29345342
TI - Frontline Science: High fat diet and leptin promote tumor progression by inducing
myeloid-derived suppressor cells.
AB - Obesity is a risk factor for cancer incidence and cancer mortality. The
association of obesity and cancer is attributed to multiple factors, but the
tightest linkage is with the chronic, low-grade inflammation that accompanies
obesity. Myeloid-derived suppressor cells (MDSC) are known facilitators of cancer
progression that act by suppressing the activation and function of tumor-reactive
T cells. Because MDSC quantity and function are driven by chronic inflammation,
we hypothesized that MDSC may accumulate in obese individuals and facilitate
tumor growth by suppressing antitumor immunity. To test this hypothesis, tumor
bearing mice on a high fat or low fat diet (HFD or LFD) were assessed for tumor
progression and the metabolic dysfunction associated with obesity. HFD enhanced
the accumulation of MDSC, and the resulting MDSC had both beneficial and
detrimental effects. HFD-induced MDSC protected mice against diet-induced
metabolic dysfunction and reduced HFD-associated inflammation, but also increased
the accumulation of fat, enhanced tumor progression, and spontaneous metastasis
and reduced survival time. HFD-induced MDSC facilitated tumor growth by limiting
the activation of tumor-reactive CD8+ T cells. Leptin, an adipokine that
regulates appetite satiety and is overexpressed in obesity, undergoes crosstalk
with MDSC in which leptin drives the accumulation of MDSC while MDSC down
regulate the production of leptin. Collectively, these studies demonstrate that
although MDSC protect against some metabolic dysfunction associated with HFD they
enhance tumor growth in HFD mice and that leptin is a key regulator linking HFD,
chronic inflammation, immune suppression, and tumor progression.
PMID- 29345343
TI - Mycobacterium tuberculosis: Rewiring host cell signaling to promote infection.
AB - The ability of Mycobacterium tuberculosis to cause disease hinges upon
successfully thwarting the innate defenses of the macrophage host cell. The
pathogen's trump card is its armory of virulence factors that throw normal host
cell signaling into disarray. This process of subverting the macrophage begins
upon entry into the cell, when M. tuberculosis actively inhibits the fusion of
the bacilli-laden phagosomes with lysosomes. The pathogen then modulates an array
of host signal transduction pathways, which dampens the macrophage's host
protective cytokine response, while simultaneously adapting host cell metabolism
to stimulate lipid body accumulation. Mycobacterium tuberculosis also renovates
the surface of its innate host cells by altering the expression of key molecules
required for full activation of the adaptive immune response. Finally, the
pathogen coordinates its exit from the host cell by shifting the balance from the
host-protective apoptotic cell death program toward a lytic form of host cell
death. Thus, M. tuberculosis exploits its extensive repertoire of virulence
factors in order to orchestrate the infection process to facilitate its growth,
dissemination, and entry into latency. This review offers critical insights into
the most recent advances in our knowledge of how M. tuberculosis manipulates host
cell signaling. An appreciation of such interactions between the pathogen and
host is critical for guiding novel therapies and understanding the factors that
lead to the development of active disease in only a subset of exposed
individuals.
PMID- 29345345
TI - Autophagy inhibition promotes phagocytosis of macrophage and protects mice from
methicillin-resistant staphylococcus aureus pneumonia.
AB - The present study is to investigate the effect of autophagy in macrophages and
the protection of mouse models against MRSA invasion, which provide new potential
therapeutic direction for lung infection. The effect of ST239 in macrophages were
analyzed by Western blot. The immunofluorescence was used to observe the
influence of autophagy inhibitor 3-MA in macrophages. Then we established MRSA
mice model and the models were divided into different groups of drugs. The effect
of autophagy in macrophage with MRSA and the changes of lung pathological in the
mouse model was analyzed by flow cytometry and immunohistochemistry. The ability
of phagocytic decreases when ST239 infected the macrophages. And the autophagy
related genes Beclin-1, LC3-I, and LC3-II protein expression significantly
increased. GFP-LC3 immunostaining showed that GFP-LC3 was significantly over
expressed in ST239-infected macrophages. Then we found the autophagy inhibitors 3
MA could make the expression of autophagy-related genes Beclin-1, LC3-I, and LC3
II decreased, the number of ST239 decreased, and the ability of macrophages
phagocytosed MRSA increasing. In the mouse model we performed the same assay, the
results showed that the percentage of macrophages in the mouse model treated with
3-MA was increased compared to the ST239 mouse model and that the number of
bacteria in right lung significantly reduced. Lung cells treated with3-MA
significantly improved the lesion of ST239 lung cell disease. Inhibition of
autophagy can increase the ability of macrophages phagocytosed MRSA, and it is a
suitable target for preventing or treating MRSA infection.
PMID- 29345346
TI - Galectin-3 type-C self-association on neutrophil surfaces; The carbohydrate
recognition domain regulates cell function.
AB - Galectin-3 is an endogenous beta-galactoside-binding lectin comprising a
carbohydrate recognition domain (CRD) linked to a collagen-like N-domain. Both
domains are required for galectin-3 to induce cellular effects; a C-terminal
fragment of galectin-3, galectin-3C, containing the CRD but lacking the N-domain,
binds cell surface glycoconjugates but does not induce cellular effects since
cross-linking promoted by the N-domain is thought to be required. Instead,
galectin-3C is proposed to antagonize the effects of galectin-3 by competing for
binding sites. The aim of this study was to investigate the effects of galectin
3C on galectin-3 interactions with human neutrophils. Recombinant galectin-3C
inhibited galectin-3-induced production of reactive oxygen species in primed
neutrophils. Surprisingly, this inhibition was not due to competitive inhibition
of galectin-3 binding to the cells. In contrast, galectin-3C potentiated galectin
3 binding, in line with emerging evidence that galectin-3 can aggregate not only
through the N-domain but also through the CRD. The cell surface interaction
between galectin-3C and galectin-3 was corroborated by colocalization of
fluorescently labeled galectin-3 and galectin-3C. Galectin-3C can be generated in
vivo through cleavage of galectin-3 by proteases. Indeed, in circulation,
galectin-3 and galectin-3C were both attached to the cell surface of neutrophils,
which displayed great capacity to bind additional galectin-3 and galectin-3C. In
conclusion, galectin-3C enhances galectin-3 binding to neutrophils by
nonactivating type-C self-association, in parallel to inhibiting neutrophil
activation by galectin-3 (induced by type-N self-association). This implicates
type-C self-association as a termination system for galectin-3-induced cell
activation, with the purpose of avoiding oxidant-dependent tissue damage.
PMID- 29345344
TI - Differential outcomes of TLR2 engagement in inflammation-induced preterm birth.
AB - Preterm birth (PTB) is the leading cause of neonatal mortality worldwide.
Infection and inflammation are considered main causes of PTB. Among multiple
pathogens, Gram-positive bacteria are commonly linked with induction of PTB.
Although activation of innate immune responses, via TLR2 engagement, by Gram
positive bacteria is a likely cause, whether induction of PTB depends on the
potency of specific microbial components to induce Toll-like receptor (TLR)2
driven inflammation has not been elucidated. Here, we show that TLR2 activation
by synthetic lipopeptides, Pam2Cys, and Pam3Cys specifically, variably influenced
inflammation and subsequent induction of PTB. Pam2Cys challenge, compared to
Pam3Cys, induced PTB and promoted significantly higher expression of inflammatory
cytokines, specifically IL-6 and IFN-beta, both in vivo and in vitro. Notably,
antibody-mediated neutralization of IL-6 or genetic deletion of type I IFN
receptor (IFNAR) was sufficient to protect from Pam2Cys-driven PTB and to temper
excessive proinflammatory cytokine production. Conversely, IFN-beta or IL-6 was
not sufficient to promote induction of PTB by Pam3Cys. In summary, our data
implies a divergent function of TLR2-activating lipopeptides in the magnitude and
type of ligand-driven inflammatory vigor in induction of PTB.
PMID- 29345347
TI - Interferons and beyond: Induction of antiretroviral restriction factors.
AB - Antiviral restriction factors are structurally and functionally diverse cellular
proteins that play a key role in the first line of defense against viral
pathogens. Although many cell types constitutively express restriction factors at
low levels, their induction in response to viral exposure and replication is
often required for potent control and repulse of the invading pathogens. It is
well established that type I IFNs efficiently induce antiviral restriction
factors. Accumulating evidence suggests that other types of IFN, as well as
specific cytokines, such as IL-27, and other activators of the cell are also
capable of enhancing the expression of restriction factors and hence to establish
an antiviral cellular state. Agents that efficiently induce restriction factors,
increase their activity, and/or render them resistant against viral antagonists
without causing general inflammation and significant side effects hold some
promise for novel therapeutic or preventive strategies. In the present review, we
summarize some of the current knowledge on the induction of antiretroviral
restriction factors and perspectives for therapeutic application.
PMID- 29345348
TI - Roles of neutrophils in cancer growth and progression.
AB - Chronic inflammation is a well-known tumor-enabling capacity, which allows
nascent tumors to acquire all the hallmark capabilities, including the escape
from immunosurveillance. Soluble and cellular inflammatory mediators constitute
the complex network of the tumor microenvironment, in which tumors grow and with
which constantly interact. Myeloid cells (e.g., tumor associated macrophages) are
pivotal players of the tumor microenvironment and are characterized by
plasticity, which consists of the ability to acquire distinct phenotypes in
response to the microenvironment in which they reside. Neutrophils are emerging
as important players of tumor microenvironment, given their heterogeneity and
plasticity. Increasing evidence suggests a dual role for neutrophils in
modulating tumor behavior and highlights the need for a reassessment of
neutrophil functions in cancer initiation and progression.
PMID- 29345349
TI - Enhanced phosphorylation of sphingosine and ceramide sustains the exuberant
proliferation of endothelial progenitors in Kaposi sarcoma.
AB - Endothelial colony-forming cells (ECFCs), a unique endothelial stem cell
population, are highly increased in the blood of Kaposi sarcoma (KS) patients. KS
derived ECFCs (KS-ECFCs) are also endowed with increased proliferative and
vasculogenic potential, thus suggesting that they may be precursors of KS spindle
cells. However, the mechanisms underlying the increased proliferative activity of
KS-ECFCs remain poorly understood. Sphingosine-1-phosphate (S1P) and ceramide-1
phosphate (C1P) are metabolically interconnected sphingoid mediators crucial to
cell proliferation. Here, we investigated the metabolism, release, and
proliferative effects of S1P and C1P in KS-ECFCs compared with control ECFCs (Ct
ECFCs). Metabolic studies by cell labeling, chromatographic analyses, and digital
autoradiography revealed that S1P and C1P biosynthesis and S1P secretion are all
efficient processes in KS-ECFCs, more efficient in KS-ECFCs than Ct-ECFCs.
Quantitative PCR analyses demonstrated a significantly higher ceramide kinase and
sphingosine kinase-2 expression in KS-ECFCs. Notably, also the expression of S1P1
and S1P3 receptors was augmented in KS-ECFCs. Accordingly, treatment with
exogenous C1P or S1P induced a significant, concentration-dependent stimulation
of KS-ECFC proliferation, but was almost completely ineffective in Ct-ECFCs.
Hence, we identified C1P and S1P as autocrine/paracrine proliferative signals in
KS-ECFCs. A better understanding of the mechanisms that enhance S1P/C1P formation
in KS-ECFCs may yield effective therapeutic modalities.
PMID- 29345350
TI - Activation of the sympathetic nervous system modulates neutrophil function.
AB - Emerging evidence has revealed that noradrenaline (NA), the main neurotransmitter
of the sympathetic nervous system (SNS), regulates a variety of immune functions
via binding to adrenergic receptors present on immune cells. In this study, we
examined the role of NA in the regulation of neutrophil functions. Neutrophils
were isolated from the bone marrow of naive mice and treated with NA at various
concentrations to assess the effect on various neutrophil functions.
Additionally, we performed cremaster intravital microscopy to examine neutrophil
endothelial cell interactions following NA superfusion in vivo. In a separate
group of animals, mice were subjected to an experimental model of stroke and at 4
and 24 h neutrophils were isolated for assessment on their ability to migrate
toward various chemokines. Treatment of neutrophils with NA for 4 h significantly
impaired neutrophil chemotaxis and induced an N2 neutrophil phenotype with
reduced expression of the genes critical for cytoskeleton remodeling and
inflammation. Prolonged NA administration promoted neutrophils to release
myeloperoxidase and IL-6, but suppressed the production of interferon-gamma and
IL-10, reduced neutrophil activation and phagocytosis. Superfusion of NA over the
cremaster muscle almost completely inhibited fMLP-induced neutrophil
adhesion/arrest and transmigration. Furthermore, using a mouse model of stroke, a
pathological condition in which SNS activation is evident, neutrophils isolated
from poststroke mice showed markedly reduced chemotaxis toward all of the
chemokines tested. The findings from our study indicate that neutrophil
chemotaxis, activation, and phagocytosis can all be negatively regulated in an NA
dependent manner. A better understanding of the relationship between sympathetic
activation and neutrophil function will be important for the development of
effective antibacterial interventions.
PMID- 29345351
TI - K313, a novel benzoxazole derivative, exhibits anti-inflammatory properties via
inhibiting GSK3beta activity in LPS-induced RAW264.7 macrophages.
AB - Benzoxazole and its derivatives have been widely studied in recent years due to
their various biological properties. A previous study has demonstrated that K313
(1H-indole-2,3-dione 3-(1,3-benzoxazol-2-ylhydrazone)), a novel benzoxazole
derivative, inhibits T cell proliferation to yield immunosuppressive effects.
However, there are no related reports about its anti-inflammatory effects. In the
present study, we investigated the anti-inflammatory properties and the
underlying molecular mechanism of K313 in lipopolysaccharide (LPS)-induced
RAW264.7 macrophages. K313 dose-dependently (5, 10, and 20 MUM) inhibited LPS
stimulated nitric oxide (NO), interleukin (IL)-6, tumor necrosis factor (TNF)
alpha, and 3-nitrotyrosine (3-NT) production and significantly decreased the gene
transcription levels of inducible nitric oxide (iNOS), IL-6, and TNF-alpha. In
addition, the results showed that the inflammatory cytokines suppressed by K313
were not regulated by p65 NF-kappaB, ERK1/2, AKT, or p38 MAPK. Instead, K313
increased phosphorylation of glycogen synthase kinase-3 beta (GSK-3beta) (Ser9)
resulting in GSK-3beta deactivation. Moreover, in LPS-stimulated RAW264.7
macrophages, K313 and lithium chloride (LiCl) had a synergistic effect on the
anti-inflammatory response. These results indicated that K313 exhibited anti
inflammatory properties and revealed the potential mechanism. K313 can increase
GSK-3beta (Ser9) phosphorylation to decrease GSK-3beta activation in LPS-induced
RAW264.7 macrophages.
PMID- 29345352
TI - Achyranthes bidentata polysaccharide suppresses osteoclastogenesis and bone
resorption via inhibiting RANKL signaling.
AB - Osteoclasts are highly differentiated multinucleated giant cells that play
fundamental roles in bone resorption and in the pathogenesis of osteolytic
conditions, such as osteoporosis and cancer-induced bone loss. Achyranthes
bidentata polysaccharide (ABP) is a hydrophilic compound with anti-oxidation and
anti-aging characteristics. The impact of ABP on RANKL-induced osteoclast
formation and bone resorption has not been assessed, hence, in this study we
investigated the effect of ABP on osteoclast formation and resorption in murine
bone marrow derived osteoclasts. We found that ABP was able to suppress RANKL
induced osteoclast differentiation and bone resorption activity at concentrations
above 6.5 uM, while demonstrating no cytotoxicity at concentrations up to 10 uM.
The actions of ABP were mediated through inhibition of RANKL-induced c-Fos and
NFATc1 gene and protein expression. Furthermore, we found that ABP suppressed
NFATc1 transcriptional activity, and the phosphorylation of MAPK pathways induced
by RANKL. Collectively, ABP attenuates RANKL-mediated osteoclast activity and
signaling, and might serve as a potential therapeutic candidate for preventing
bone loss related diseases.
PMID- 29345353
TI - HipOP mesenchymal population has high potential for repairing injured peripheral
nerves.
AB - Bone marrow stromal cells (BMSCs) are reportedly a heterogeneous population of
mesenchymal stem cells (MSCs). Recently, we developed a simple strategy for the
enrichment of MSCs with the capacity to differentiate into osteoblasts,
chondrocytes, and adipocytes. On transplantation, the progenitor-enriched
fractions can regenerate the bone with multiple lineages of donor origin and are
thus called "highly purified osteoprogenitors" (HipOPs). Although our previous
studies have demonstrated that HipOPs are enriched with MSCs and exhibit a higher
potential to differentiate into osteoblasts, adipocytes, and chondrocytes than
BMSCs, their potential to differentiate into neural cells has not been clarified.
In this study, we evaluated the efficacy of HipOPs as a resource of neural stem
cells. The neurosphere assay showed that neurospheres formed by HipOPs exhibited
self-renewal ability and their size was generally larger than that of
neurospheres formed by BMSCs. A limiting dilution assay was used to evaluate the
frequency of neural progenitors in BMSCs and HipOPs. The results demonstrated
that the frequency of neural progenitors in HipOPs was 120-fold higher than that
in BMSCs. Furthermore, to investigate the in vivo regenerative potential of the
peripheral nerve, we modified a murine peripheral nerve injury experimental model
and demonstrated that HipOPs exhibit a higher efficacy in repairing injured
peripheral nerves. These findings suggest that HipOPs are a useful cell resource
for regenerative therapies such as that in case of peripheral nerve injury.
PMID- 29345354
TI - Lack of functional selectin-ligand interactions enhances innate immune resistance
to systemic Listeria monocytogenes infection.
AB - Selectin-ligand interactions are important for leukocyte homing and
functionality. The roles of selectin-ligand interactions in modulating immunity
to intracellular infections are not completely understood. Mice lacking the
expression of fucosyltransferase-IV and -VII (Fucosyltransferase-IV and -VII
double knockout, FtDKO) exhibit deficient functionality of selectin-ligand
interactions. We addressed the kinetics of infection and immunity to Listeria
monocytogenes (LM), an intracellular pathogen, in FtDKO mice. These mice
exhibited enhanced ability to clear infection and increased survival to a lethal
dose of LM infection relative to wild-type (WT) C57BL/6J controls. This was
associated with increased levels of neutrophils, monocytes, and dendritic cells
(DCs) in the blood and/or infected organs. Adoptive transfer of bone marrow (BM)
cells from FtDKO mice to WT mice resulted in enhanced neutrophil numbers and
improved clearance of LM bacteria in recipients. In vivo depletion of myeloid
innate immune cells, particularly neutrophils, monocytes, macrophages, and DCs,
using anti-Ly-6G (RB6-8C5) monoclonal antibody, reduced the ability of FtDKO mice
to curtail LM infection. Nevertheless, depletion using anti-Ly-6G (1A8) known to
exclusively deplete neutrophils did not abrogate increased resistance of FtDKO
mice to LM infection, suggesting a role for other myeloid innate immune cells in
this model. Examination of BM hematopoietic progenitors through flow cytometry
and cell culture colony-forming unit assay showed increased frequencies of
granulocyte-macrophage progenitors in FtDKO relative to WT mice, Overall, our
results indicate that functional selectin ligand deficiency enhances innate
immune-mediated resistance to systemic LM infection despite defective leukocyte
migration and lymphocyte homing.
PMID- 29345355
TI - Effects of antioxidants on apoptosis induced by dasatinib and nilotinib in K562
cells.
AB - In clinical practice for the treatment of chronic myeloid leukemia, second
generation of tyrosine kinase inhibitors such as Nilotinib (NIL) specific and
potent inhibitor of the BCR/ABL kinase and Dasatinib (DAS) a inhibitor of BCR/ABL
and Src family kinase were developed to clinically overcome imatinib resistance.
In this study, we wanted to test the ability of some antioxidants such
Resveratrol (RES) or a new recombinant mitochondrial manganese containing
superoxide dismutase (rMnSOD) or delta-tocotrienol (delta-TOCO) to interact with
DAS and NIL on viability, reactive oxygen species (ROS) production, lipid
peroxidation, and apoptosis. To test the possible mechanisms of action of such
antioxidants, we utilized N-acetyl-L-cysteine (NAC) a specific inhibitor ROS
production or PP1 a specific Src tyrosine kinase inhibitor or BAPTA a specific
chelator of intracellular calcium. Our data demonstrated: 1) RES, rMnSOD, delta
TOCO, and NAC, at dose used, significantly reduced the intracellular levels of
MDA induced by DAS or NIL; 2) RES, rMnSOD, and delta-TOCO increased the
intracellular ROS levels; 3) The increase ROS levels is related to higher levels
of oligonucleosomesi induced by DAS and NIL and that NAC significantly reduced
this activity. Interestingly, our data showed that apoptotic activity of DAS and
NIL have significantly increased the production of oligonucleosomes by triggering
excessive ROS generation as well as functionality of SERCA receptors.
PMID- 29345356
TI - Ethical and Practical Considerations in the Use of a Predictive Model to Trigger
Suicide Prevention Interventions in Healthcare Settings.
AB - Predictive models that utilize data from electronic healthcare records (EHR) have
been developed, investigated, and appear to provide an important resource for
suicide prevention in medical settings. Actuarial approaches to predicting
suicide may be particularly important given the relative inability of clinicians
to accurately predict suicide. Although research regarding predictive models that
utilize EHR is certainly promising, ethical considerations for the use of these
models to trigger suicide prevention interventions warrant careful consideration.
The current manuscript discusses ethical considerations regarding the use of
predictive models in suicide prevention clinical care. The unique characteristics
of suicide are explored in terms of how they inform ethical and practical
approaches. Additionally, biomedical ethical principles and utilitarian, Kantian,
and personal rights ethical models are applied to the topic. Recommendations for
navigating the ethical issues are provided as an initial framework for others who
are considering the implementation of a predictive model to trigger suicide
prevention initiatives.
PMID- 29345358
TI - Editorial: Two MDSC faces in obesity: Correcting metabolic dysfunctions but
promoting tumor development.
PMID- 29345357
TI - The prognostic value of PI3K mutational status in breast cancer: A meta-analysis.
AB - Breast cancer (BC) is the second most common cause of cancer-related deaths in
women worldwide. The availability of reliable biomarkers of response/resistance
to cancer treatments would benefit patients and clinicians allowing for a better
selection of BC patients most likely to respond to a specific treatment.
Phosphatidylinositol 3-kinase (PI3K) enzymes are involved in numerous cellular-
functions and processes. The gene encoding for PI3K catalytic subunit p110alpha
is mutated in 20-40% of BC. We performed a meta-analysis of the current
literature on randomized clinical trials, investigating the role of PIK3CA
mutational status as prognostic factor, and predictor of response to anti-cancer
treatments. Overall 1929 cases were included. The pooled analysis confirmed that
the presence of a PIK3CA mutation represents an independent negative prognostic
factor (HR = 1.67, 95%CI: 1.15-2.43; P = 0.007) in BC, as previously reported. As
PI3K signaling is also a result of other pathways' hyperactivation, further
investigation of potential biomarkers able to predict likelihood of response to
anti-PI3K/mTOR, anti-HER2, and other TKRs is warranted in future randomized
clinical trials.
PMID- 29345359
TI - PDZ proteins are expressed and regulated in antigen-presenting cells and are
targets of influenza A virus.
AB - In this work, we identified the expression, regulation, and viral targeting of
Scribble and Dlg1 in antigen-presenting cells. Scribble and Dlg1 belong to the
family of PDZ (postsynaptic density (PSD95), disc large (Dlg), and zonula
occludens (ZO-1)) proteins involved in cell polarity. The relevance of PDZ
proteins in cellular functions is reinforced by the fact that many viruses
interfere with host PDZ-dependent interactions affecting cellular mechanisms thus
favoring viral replication. The functions of Scribble and Dlg have been widely
studied in polarized cells such as epithelial and neuron cells. However, within
the cells of the immune system, their functions have been described only in T and
B lymphocytes. Here we demonstrated that Scribble and Dlg1 are differentially
expressed during antigen-presenting cell differentiation and dendritic cell
maturation. While both Scribble and Dlg1 seem to participate in distinct
dendritic cell functions, both are targeted by the viral protein NS1 of influenza
A in a PDZ-dependent manner in dendritic cells. Our findings suggest that these
proteins might be involved in the mechanisms of innate immunity and/or antigen
processing and presentation that can be hijacked by viral pathogens.
PMID- 29345360
TI - mTOR: A double-edged sword for diabetes.
AB - Diabetes is both a metabolic and an immune disorder. One intriguing link between
the two is the serine-threonine protein kinase mammalian target of rapamycin
(mTOR). As a component of the PI3K/Akt pathway and other cellular signals, mTOR
is a key regulator of fuel metabolism and function of both pancreatic islet beta
cells and immune cells. Consequently, it seems that mTOR has both anti- and
prodiabetic effects. On the one hand, activation of mTOR in beta cells can
increase their growth and proliferation, opposing impairments of insulin
secretion in diabetes. On the other, activation of mTOR signaling in specific
immune cells alters their fuel metabolism, amplifying their contributions to beta
cell dysfunction, contributing to the development of diabetes. In this review, we
focus on roles of mTOR signaling in pancreatic beta cells and immune cells and
their implications in the pathogenesis and treatment of diabetes.
PMID- 29345361
TI - Immunotherapy for cardiovascular disease.
AB - Heart failure (HF), the final stage of pathological cardiac hypertrophy, is a
major cause of hospitalization and mortality. The role of inflammation in the
pathogenesis of HF has been extensively studied, with great emphasis on
proinflammatory cytokines. Yet, clinical trials targeting these cytokines failed
to become a credible therapeutic strategy for HF. More recent studies are
increasingly highlighting an active role for T cells in the progression of HF
pathology. As a result, a number of novel immunotherapy strategies are emerging
for the treatment of HF and other cardiovascular diseases, via the targeting of
adaptive immunity. Here we provide an overview of the background, details, and
expected outcomes of these attempts.
PMID- 29345362
TI - Innate lymphoid cells in antitumor immunity.
AB - Innate lymphoid cells (ILCs) are the most recently characterized subset of innate
lymphocytes. Based on their specific transcriptional regulation, cytokine
secretion pattern and effector functions ILCs mirror the different CD4 T helper
cell subsets, with the unique attributes of acting locally in early phases of
immune responses, in an antigen-independent manner. In this review, we discuss
how ILCs have been implicated in tumorigenesis. Their presence might favor or
inhibit tumor growth, depending on the cytokines released and the specific tumor
microenvironment. As our understanding of ILCs' contribution to antitumor
responses advances, clinical options to target ILCs in antitumor therapies are
also emerging.
PMID- 29345363
TI - Effects of IL-10 and Th 2 cytokines on human Mphi phenotype and response to CSF1R
inhibitor.
AB - Tumor-associated Mphis display a plastic phenotype that is regulated by the local
tumor milieu. Gene expression analysis and functional characterization of Mphis
exposed in vitro to individual cytokines aids to delineate the cross-talk between
defined cytokines shaping the complex Mphi phenotype. Human monocyte-derived
Mphis can be differentiated in vitro with the T helper cell type 2 response
cytokines IL-4 and IL-13 or the immunosuppressive IL-10. Notably, only the latter
subset undergoes apoptosis when treated with the CSF 1 receptor (CSF1R) blocking
antibody emactuzumab. However, under physiologic conditions, the Mphi phenotype
is regulated by cytokine combination. Hence, in this study, we characterized the
plasticity of IL-4 or IL-13-differentiated Mphis upon exposure to the
immunosuppressive IL-10. Although IL-4-differentiated Mphis sustained their
molecular phenotype in the presence of IL-10, IL-13-differentiated Mphis were
skewed towards the IL-10 phenotype. Gene expression profiling revealed unique IL
4+IL-10 and IL-13+IL-10 Mphi signatures associated with up-regulation of
canonical NF-kappaB or Wnt/beta-catenin signaling pathways, respectively.
Although IL-10 was able to alter the surface marker and gene expression profile
of IL-13-differentiated Mphis, addition of IL-10 did not restore emactuzumab
susceptibility. Combining NF-kappaB and Wnt/beta-catenin signaling inhibitors
with emactuzumab had no effect on viability. On average 3-5% of cancer patients
overexpressed IL-4, IL-13, or IL-10 mRNA in silico. Although a small patient
subset overexpressed IL-10+IL-13, IL-4+IL-10 lacked co-expression. In vitro
characterization of CSF1R inhibitor-refractory Mphi phenotypes can support novel
pharmacological approaches to specifically target these cells.
PMID- 29345364
TI - The N-terminal peptide moiety of the Mycobacterium tuberculosis 19 kDa
lipoprotein harbors RP105-agonistic properties.
AB - Radioprotective 105 kDa (RP105, CD180) is a member of the Toll-like receptor
(TLR) family that interacts with TLR2 and facilitates recognition of mature
lipoproteins expressed by Mycobacterium tuberculosis and Mycobacterium bovis BCG.
In this study, we used synthetic lipopeptide analogs of the M. tuberculosis 19
kDa lipoprotein to define structural characteristics that promote RP105-mediated
host cell responses. A tripalmitoylated lipopeptide composed of the first 16 N
terminal amino acids of the M. tuberculosis 19 kDa lipoprotein induced RP105
dependent TNF and IL-6 production by macrophages. Di- and tripalmitoylated
variants of this lipopeptide elicited an equivalent RP105-dependent response,
indicating that while the lipid moiety is required for macrophage activation, it
is not a determinant of RP105 dependency. Instead, substitution of two polar
threonine residues at positions 7 and 8 with nonpolar alanine residues resulted
in reduced RP105 dependency. These results strongly suggest that the amino acid
composition of the M. tuberculosis 19 kDa lipoprotein, and likely other
mycobacterial lipoproteins, is a key determinant of RP105 agonism.
PMID- 29345365
TI - Deletion of BCG Hip1 protease enhances dendritic cell and CD4 T cell responses.
AB - Dendritic cells (DCs) play a key role in the generation of CD4 T cell responses
to pathogens. Mycobacterium tuberculosis (Mtb) harbors immune evasion mechanisms
that impair DC responses and prevent optimal CD4 T cell immunity. The vaccine
strain Mycobacterium bovis Bacille Calmette-Guerin (BCG) shares many of the
immune evasion proteins utilized by Mtb, but the role of these proteins in DC and
T cell responses elicited by BCG is poorly understood. We previously reported
that the Mtb serine protease, Hip1, promotes sub-optimal DC responses during
infection. Here, we tested the hypothesis that BCG Hip1 modulates DC functions
and prevents optimal antigen-specific CD4 T cell responses that limit the
immunogenicity of BCG. We generated a strain of BCG lacking hip1 (BCGDeltahip1)
and show that it has superior capacity to induce DC maturation and cytokine
production compared with the parental BCG. Furthermore, BCGDeltahip1-infected DCs
were more effective at driving the production of IFN-gamma and IL-17 from antigen
specific CD4 T cells in vitro. Mucosal transfer of BCGDeltahip1-infected DCs into
mouse lungs induced robust CD4 T cell activation in vivo and generated antigen
specific polyfunctional CD4 T cell responses in the lungs. Importantly,
BCGDeltahip1-infected DCs enhanced control of pulmonary bacterial burden
following Mtb aerosol challenge compared with the transfer of BCG-infected DCs.
These results reveal that BCG employs Hip1 to impair DC activation, leading to
attenuated lung CD4 T cell responses with limited capacity to control Mtb burden
after challenge.
PMID- 29345366
TI - Interactions between the microbiota and innate and innate-like lymphocytes.
AB - The microbiota, which consists of commensal bacteria, fungi, and viruses, limits
the colonization of pathogens at barrier tissues and promotes immune homeostasis.
The latter is accomplished through the induction and regulation of both innate
and adaptive immune responses. Innate lymphocytes, which include the type-1
innate lymphoid cell (ILC1), NK cell, type-2 innate lymphoid cell (ILC2), type-3
innate lymphoid cell (ILC3), and lymphoid tissue inducer (LTi) cell populations,
and innate-like lymphocytes, such as NKT cells, mucosal-associated invariant T
(MAIT) cells, and gammadelta T cells, are uniquely capable of responding to the
microbiota due to their tissue localization and rapid primary responses. In turn,
through their effector functions, these lymphocyte populations modulate the
composition of the microbiota and maintain the segregation of commensals. This
review will focus on how innate and innate-like lymphocytes mediate the crosstalk
with the microbiome.
PMID- 29345367
TI - CD300 family receptors regulate eosinophil survival, chemotaxis, and effector
functions.
AB - The CD300 family of receptors is an evolutionary conserved receptor family that
belongs to the Ig superfamily and is expressed predominantly by the myeloid
lineage. Over the past couple of years, accumulating data have shown that
eosinophils express various Ig superfamily receptors that regulate key
checkpoints in their biology including their maturation, transition from the bone
marrow to the peripheral blood, migration, adhesion, survival, and effector
functions in response to numerous activating signals such as IL-4, IL-33, and
bacteria. In this review, we will present the emerging roles of CD300 family
receptors and specifically CD300a and CD300f in the regulation of these
eosinophil activities. The structure and expression pattern of these molecules
will be discussed and their involvement in suppressing or co-activating
eosinophil functions in health and disease will be illustrated.
PMID- 29345368
TI - Therapeutic effect of Lipoxin A4 in malaria-induced acute lung injury.
AB - Acute lung injury (ALI) models are characterized by neutrophil accumulation,
tissue damage, alteration of the alveolar capillary membrane, and physiological
dysfunction. Lipoxin A4 (LXA4 ) is an anti-inflammatory eicosanoid that was
demonstrated to attenuate lipopolysaccharide-induced ALI. Experimental models of
severe malaria can be associated with lung injury. However, to date, a putative
effect of LXA4 on malaria (M)-induced ALI has not been addressed. In this study,
we evaluated whether LXA4 exerts an effect on M-ALI. Male C57BL/6 mice were
randomly assigned to the following five groups: noninfected; saline-treated
Plasmodium berghei-infected; LXA4 -pretreated P. berghei-infected (LXA4
administered 1 h before infection and daily, from days 0 to 5 postinfection),
LXA4 - and LXA4 receptor antagonist BOC-2-pretreated P. berghei-infected; and
LXA4 -posttreated P. berghei-infected (LXA4 administered from days 3 to 5
postinfection). By day 6, pretreatment or posttreatment with LXA4 ameliorate
lung mechanic dysfunction reduced alveolar collapse, thickening and interstitial
edema; impaired neutrophil accumulation in the pulmonary tissue and blood; and
reduced the systemic production of CXCL1. Additionally, in vitro treatment with
LXA4 prevented neutrophils from migrating toward plasma collected from P. berghei
infected mice. LXA4 also impaired neutrophil cytoskeleton remodeling by
inhibiting F-actin polarization. Ex vivo analysis showed that neutrophils from
pretreated and posttreated mice were unable to migrate. In conclusion, we
demonstrated that LXA4 exerted therapeutic effects in malaria-induced ALI by
inhibiting lung dysfunction, tissue injury, and neutrophil accumulation in lung
as well as in peripheral blood. Furthermore, LXA4 impaired the migratory ability
of P. berghei-infected mice neutrophils.
PMID- 29345369
TI - Memory B cell heterogeneity: Remembrance of things past.
AB - B cells that persist for long periods of time after antigen encounter exist as
either antibody-producing plasma cells (long-lived plasma cells, LLPCs) that
reside primarily in the bone marrow or rapidly responsive memory B cells (MBCs)
that reside in the spleen and circulation. Although LLPCs are thought to be non
responsive to a secondary infection, MBCs respond to subsequent infection through
the production of antibody-secreting cells, formation of new germinal centers
(GCs), and repopulation of the memory pool. Dogma suggests that MBCs express
class-switched, somatically hypermutated BCRs after undergoing a GC reaction. Yet
this narrow view of MBCs has been challenged over the years and it is now well
recognized that diverse MBC subsets exist in both rodents and humans. Here, we
review current thoughts on the phenotypic and functional characteristics of MBCs,
focusing on a population of somatically hypermutated, high affinity IgM+ MBCs
that are rapidly responsive to a secondary malaria infection.
PMID- 29345371
TI - Therapeutic manipulation of host cell death pathways to facilitate clearance of
persistent viral infections.
AB - Most persistent viral infections can be controlled, but not cured, by current
therapies. Abrogated antiviral immunity and stable latently infected cells
represent major barriers to cure. This necessitates life-long suppressive
antiviral therapy. Achieving a cure for HIV, hepatitis B virus, Epstein Barr
virus, and others, requires novel approaches to facilitate the clearance of
infected cells from the host. One such approach is to target host cell death
pathways, rather than the virus itself. Here, we summarize recent findings from
studies that have utilized therapeutics to manipulate host cell death pathways as
a means to treat and cure persistent viral infections.
PMID- 29345370
TI - Inhibition of soluble epoxide hydrolase attenuates eosinophil recruitment and
food allergen-induced gastrointestinal inflammation.
AB - Prevalence of food allergies in the United States is on the rise. Eosinophils are
recruited to the intestinal mucosa in substantial numbers in food allergen-driven
gastrointestinal (GI) inflammation. Soluble epoxide hydrolase (sEH) is known to
play a pro-inflammatory role during inflammation by metabolizing anti
inflammatory epoxyeicosatrienoic acids (EETs) to pro-inflammatory diols. We
investigated the role of sEH in a murine model of food allergy and evaluated the
potential therapeutic effect of a highly selective sEH inhibitor (trans-4-{4-[3
(4-trifluoromethoxyphenyl)-ureido]-cyclohexyloxy}-benzoic acid [t-TUCB]). Oral
exposure of mice on a soy-free diet to soy protein isolate (SPI) induced
expression of intestinal sEH, increased circulating total and antigen-specific
IgE levels, and caused significant weight loss. Administration of t-TUCB to SPI
challenged mice inhibited IgE levels and prevented SPI-induced weight loss.
Additionally, SPI-induced GI inflammation characterized by increased recruitment
of eosinophils and mast cells, elevated eotaxin 1 levels, mucus hypersecretion,
and decreased epithelial junction protein expression. In t-TUCB-treated mice,
eosinophilia, mast cell recruitment, and mucus secretion were significantly lower
than in untreated mice and SPI-induced loss of junction protein expression was
prevented to variable levels. sEH expression in eosinophils was induced by
inflammatory mediators TNF-alpha and eotaxin-1. Treatment of eosinophils with t
TUCB significantly inhibited eosinophil migration, an effect that was mirrored by
treatment with 11,12-EET, by inhibiting intracellular signaling events such as
ERK (1/2) activation and eotaxin-1-induced calcium flux. These studies suggest
that sEH induced by soy proteins promotes allergic responses and GI inflammation
including eosinophilia and that inhibition of sEH can attenuate these responses.
PMID- 29345372
TI - Truncation of neurokinin-1 receptor-Negative regulation of substance P signaling.
AB - Substance P (SP) is a tachykinin peptide, which triggers intracellular signaling
in the nervous and immune systems, as well as, other local and systemic events.
The interaction between SP and its receptor, neurokinin-1 receptor (NK1R),
results in major downstream cellular actions, which include changes in calcium
fluxes, ERK, and p21-activated kinase phosphorylation and NFkappaB activation.
Two naturally occurring variants of the NK1R, the full-length, 407 aa receptor
(NK1R-F) and the truncated, 311 aa isoform (NK1R-T), mediate the actions of SP.
Receptor truncation partially disrupts signaling motifs of the carboxyl tail, a
critical site for mediating NK1R signaling, resulting in a "less-efficient"
receptor. Although NK1R-F is the predominant isoform in the central and
peripheral nervous systems, NK1R-T is expressed in several tissues and cells,
which include monocytes, NK cells, and T-cells. The SP binding domain is not
affected by truncation and this site is identical in both NK1R receptor isoforms.
However, while cells expressing NK1R-F respond to nanomolar concentrations of SP,
monocyte and macrophage activation, mediated through NK1R-T, requires micromolar
concentrations of SP in order to elicit signaling responses. Elevated plasma
levels of SP are associated with increased inflammatory responses and NK1R
antagonists reduce inflammation and cytokine production in vivo. This mini review
presents and discusses the novel hypothesis that the expression of NK1R-T on
immune system cells prevents immune activation in a milieu, which usually
contains low concentrations of SP and, thus, maintains immune homeostasis. In
contrast, in the activated neuronal microenvironment, when SP levels reach the
threshold at tissue sites, SP promotes immune activation and modulates
monocyte/macrophage polarization.
PMID- 29345373
TI - Macrophage instructs neutrophil death.
PMID- 29345374
TI - SHIP negatively regulates type II immune responses in mast cells and macrophages.
AB - SHIP is a hematopoietic-specific lipid phosphatase that dephosphorylates PI3K
generated PI(3,4,5)-trisphosphate. SHIP removes this second messenger from the
cell membrane blunting PI3K activity in immune cells. Thus, SHIP negatively
regulates mast cell activation downstream of multiple receptors. SHIP has been
referred to as the "gatekeeper" of mast cell degranulation as loss of SHIP
dramatically increases degranulation or permits degranulation in response to
normally inert stimuli. SHIP also negatively regulates Mphi activation, including
both pro-inflammatory cytokine production downstream of pattern recognition
receptors, and alternative Mphi activation by the type II cytokines, IL-4, and IL
13. In the SHIP-deficient (SHIP-/- ) mouse, increased mast cell and Mphi
activation leads to spontaneous inflammatory pathology at mucosal sites, which is
characterized by high levels of type II inflammatory cytokines. SHIP-/- mast
cells and Mphis have both been implicated in driving inflammation in the SHIP-/-
mouse lung. SHIP-/- Mphis drive Crohn's disease-like intestinal inflammation and
fibrosis, which is dependent on heightened responses to innate immune stimuli
generating IL-1, and IL-4 inducing abundant arginase I. Both lung and gut
pathology translate to human disease as low SHIP levels and activity have been
associated with allergy and with Crohn's disease in people. In this review, we
summarize seminal literature and recent advances that provide insight into SHIP's
role in mast cells and Mphis, the contribution of these cell types to pathology
in the SHIP-/- mouse, and describe how these findings translate to human disease
and potential therapies.
PMID- 29345375
TI - Understanding the regulation of APOBEC3 expression: Current evidence and much to
learn.
AB - The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3)
family of cytosine deaminases plays crucial roles in innate immunity through the
ability of restricting viral replication by deamination and mutation of viral
genomes. The antiviral function of these proteins was first discovered when
research in the field of HIV infection revealed that one member of the family,
namely APOBEC3G, restricts HIV infection in T lymphocytes and that the viral
infectivity factor protein drives the proteosomal degradation of this enzyme,
thus overriding its antiviral function. Recent advances in cancer genomics,
together with biochemical characterization of the APOBEC3 enzymes, have now
implicated some family members in somatic mutagenesis during carcinogenesis.
While several studies investigated the downstream consequences of APOBEC3
expression and activity, either in the context of viral infection or
tumorigenesis, little is known on the upstream mechanisms regulating APOBEC3
expression. Such knowledge would be of huge importance in developing innovative
approaches to strengthen antiviral innate immunity on one side and to prevent
cancer development on the other. This mini review summarizes research advances on
the molecular mechanisms regulating the expression of APOBEC3 family members in
selected immune cell populations and cancer cells.
PMID- 29345377
TI - Flexoelectricity in Bones.
AB - Bones generate electricity under pressure, and this electromechanical behavior is
thought to be essential for bone's self-repair and remodeling properties. The
origin of this response is attributed to the piezoelectricity of collagen, which
is the main structural protein of bones. In theory, however, any material can
also generate voltages in response to strain gradients, thanks to the property
known as flexoelectricity. In this work, the flexoelectricity of bone and pure
bone mineral (hydroxyapatite) are measured and found to be of the same order of
magnitude; the quantitative similarity suggests that hydroxyapatite
flexoelectricity is the main source of bending-induced polarization in cortical
bone. In addition, the measured flexoelectric coefficients are used to calculate
the (flexo)electric fields generated by cracks in bone mineral. The results
indicate that crack-generated flexoelectricity is theoretically large enough to
induce osteocyte apoptosis and thus initiate the crack-healing process,
suggesting a central role of flexoelectricity in bone repair and remodeling.
PMID- 29345376
TI - Role of negative regulation of immune signaling pathways in neutrophil function.
AB - Polymorphonuclear neutrophils (PMNs) play a critical role in host defense against
infection and in the resolution of inflammation. However, immune responses
mediated by PMN must be tightly regulated to facilitate elimination of invading
pathogens without inducing detrimental inflammation and host tissue damage.
Specific engagement of cell surface immunoreceptors by a diverse range of
extracellular signals regulates PMN effector functions through differential
activation of intracellular signaling cascades. Although mechanisms of PMN
activation mediated via cell signaling pathways have been well described, less is
known about negative regulation of PMN function by immune signaling cascades.
Here, we provide an overview of immunoreceptor-mediated negative regulation of
key PMN effector functions including maturation, migration, phagocytosis,
reactive oxygen species release, degranulation, apoptosis, and NET formation.
Increased understanding of mechanisms of suppression of PMN effector functions
may point to possible future therapeutic targets for the amelioration of PMN
mediated autoimmune and inflammatory diseases.
PMID- 29345378
TI - Self-Calibrating Mechanochromic Fluorescent Polymers Based on Encapsulated
Excimer-Forming Dyes.
AB - While mechanochemical transduction principles are omnipresent in nature,
mimicking these in artificial materials is challenging. The ability to reliably
detect the exposure of man-made objects to mechanical forces is, however, of
great interest for many applications, including structural health monitoring and
tamper-proof packaging. A useful concept to achieve mechanochromic responses in
polymers is the integration of microcapsules, which rupture upon deformation and
release a payload causing a visually detectable response. Herein, it is reported
that this approach can be used to create mechanochromic fluorescent materials
that show a direct and ratiometric response to mechanical deformation. This can
be achieved by filling poly(urea-formaldehyde) microcapsules with a solution of a
photoluminescent aggregachromic cyano-substituted oligo(p-phenylene vinylene) and
embedding these particles in poly(dimethylsiloxane). The application of
mechanical force by way of impact, incision, or tensile deformation opens the
microcapsules and releases the fluorophore in the damaged area. Due to excimer
formation, the subsequent aggregation of the dye furnishes a detectable
fluorescence color change. With the emission from unopened microcapsules as built
in reference, the approach affords materials that are self-calibrating. This new
concept appears to be readily applicable to a range of polymer matrices and
allows for the straightforward assessment of their structural integrity.
PMID- 29345379
TI - Sphingolipids role in the regulation of inflammatory response: From leukocyte
biology to bacterial infection.
AB - Sphingolipids (SLs) are amphiphilic molecules mainly associated with the external
leaflet of eukaryotic plasma membrane, and are structural membrane components
with key signaling properties. Since the beginning of the last century, a large
number of papers described the involvement of these molecules in several aspects
of cell physiology and pathology. Several lines of evidence support the critical
role of SLs in inflammatory diseases, by acting as anti- or pro-inflammatory
mediators. They are involved in control of leukocyte activation and migration,
and are recognized as essential players in host response to pathogenic infection.
We propose here a critical overview of current knowledge on involvement of
different classes of SLs in inflammation, focusing on the role of simple and
complex SLs in pathogen-mediated inflammatory response.
PMID- 29345380
TI - CIRP increases ICAM-1+ phenotype of neutrophils exhibiting elevated iNOS and NETs
in sepsis.
AB - Sepsis represents uncontrolled inflammation due to an infection. Cold-inducible
RNA-binding protein (CIRP) is a stress-induced damage-associated molecular
pattern (DAMP). A subset of neutrophils expressing ICAM-1+ neutrophils was
previously shown to produce high levels of reactive oxygen species. The role of
CIRP for the development and function of ICAM-1+ neutrophils during sepsis is
unknown. We hypothesize that CIRP induces ICAM-1 expression in neutrophils
causing injury to the lungs during sepsis. Using a mouse model of cecal ligation
and puncture (CLP)-induced sepsis, we found increased expression of CIRP and
higher frequencies and numbers of ICAM-1+ neutrophils in the lungs. Conversely,
the CIRP-/- mice showed significant inhibition in the frequencies and numbers of
ICAM-1+ neutrophils in the lungs compared to wild-type (WT) mice in sepsis. In
vitro treatment of bone marrow-derived neutrophils (BMDN) with recombinant murine
CIRP (rmCIRP) significantly increased ICAM-1+ phenotype in a time- and dose
dependent manner. The effect of rmCIRP on increasing frequencies of ICAM-1+
neutrophils was significantly attenuated in BMDN treated with anti-TLR4 Ab or NF
kappaB inhibitor compared, respectively, with BMDN treated with isotype IgG or
DMSO. The frequencies of iNOS producing and neutrophil extracellular traps (NETs)
forming phenotypes in rmCIRP-treated ICAM-1+ BMDN were significantly higher than
those in ICAM-1- BMDN. Following sepsis the ICAM-1+ neutrophils in the lungs
showed significantly higher levels of iNOS and NETs compared to ICAM-1-
neutrophils. We further revealed that ICAM-1 and NETs were co-localized in the
neutrophils treated with rmCIRP. CIRP-/- mice showed significant improvement in
their survival outcome (78% survival) over that of WT mice (48% survival) in
sepsis. Thus, CIRP could be a novel therapeutic target for regulating iNOS
producing and NETs forming ICAM-1+ neutrophils in the lungs during sepsis.
PMID- 29345381
TI - Durable lesion formation while avoiding esophageal injury during ablation of
atrial fibrillation: Lessons learned from late gadolinium MR imaging.
AB - INTRODUCTION: Adequate catheter/atrial tissue contact is critical for lesion
formation during radiofrequency (RF) ablation of atrial fibrillation (AF). Late
gadolinium enhancement magnetic resonance imaging (LGE-MRI) is a unique tool for
the evaluation of lesion formation and detection of acute esophageal injury.
METHODS: LGE-MRIs were obtained prior, within 24 hours of, and at 115 +/- 62 days
after first AF ablation in 36 patients. The Visitag module of CARTO3 was used to
collect contact force (CF) and duration from a CF sensing ablation catheter for
each registered ablation point. The minimum CF resulting in permanent lesions was
determined. Esophageal enhancement detected by acute LGE-MRI was classified as
mild, moderate, and severe. The CF resulting in esophageal enhancement was
determined. RESULTS: A total of 4,642 registered ablation tags at 50 W power were
analyzed. The mean RF duration (5.9 +/- 3.7 vs. 5.6 +/- 3.2 seconds, P < 0.05),
CF (11.5 +/- 5.6 vs. 10.9 +/- 5.4 g, P < 0.001), and force time integral (FTI)
(67.3 +/- 54.5 vs. 62.2 +/- 52.7 gs, P < 0.01) were significantly higher between
ablation tags with and without associated LGE-MRI detected scar. The mean CF
(15.7 +/- 6.1 vs. 12.6 +/- 5.9 g, P < 0.05, n = 17 patients) in areas of
esophageal enhancement was greater than areas without. CONCLUSION: Left atrial
short duration ablation lesions with a CF greater than 12 g are more likely to be
associated with permanent lesion formation. Ablating on top of the esophagus, CF
less than 15 g would help minimize esophageal wall injury.
PMID- 29345382
TI - Overweight and obesity in patients with atrial fibrillation: Sex differences in 1
year outcomes in the EORP-AF General Pilot Registry.
AB - BACKGROUND: The impact of overweight and obesity on outcomes in "real world"
patients with atrial fibrillation (AF) is not fully defined. Second, sex
differences in AF outcomes may also exist. METHODS AND RESULTS: The aim was to
investigate outcomes at 1 year follow-up for AF patients enrolled in the EORP-AF
Registry, according to BMI (kg/m2 ), comparing patients with normal BMI (18.5 to
< 25 kg/m2 ), overweight (25 to < 30 kg/m2 ) and obesity (>= 30 kg/m2 ), in
relation to sex differences. Among 2,540 EORP AF patients (38.9% female; median
age 69) with 1 year follow-up data available, 720 (28.3%) had a normal BMI, 1,084
(42.7%) were overweight, and 736 (29.0%) were obese. Obese patients were younger
and with more prevalent diabetes mellitus and hypertension (P < 0. 001). One-year
outcomes showed that all-cause mortality was significantly different according to
BMI among female patients (9.3% normal BMI, 5.3% overweight, and 4.3 % obese, P =
0.023), but not among male patients (P = 0.748). The composite outcome of
thromboembolic events and death was also significantly different, being lower in
obese females (P = 0.035). Among male patients, bleeding events were
significantly more frequent in obese subjects (P = 0.035). On multivariable Cox
analysis, BMI was not independently associated with all-cause mortality.
CONCLUSIONS: Among AF patients, overweight and obesity are common and associated
with better outcomes in females (a finding previously reported as "obesity
paradox"), while no significant differences in outcomes are detected among male
patients. Final multivariable model found that increasing BMI was not associated
with increased risk of all-cause death; conversely, age and comorbidities
persisted as major determinants.
PMID- 29345383
TI - Interesting mode of initiation of LBBB tachycardia: What is the mechanism?
PMID- 29345384
TI - A Single-Molecule Propyne Trap: Highly Efficient Removal of Propyne from
Propylene with Anion-Pillared Ultramicroporous Materials.
AB - Propyne/propylene (C3 H4 /C3 H6 ) separation is a critical process for the
production of polymer-grade C3 H6 . However, optimization of the structure of
porous materials for the highly efficient removal of C3 H4 from C3 H6 remains
challenging due to their similar structures and ultralow C3 H4 concentration.
Here, it is first reported that hybrid ultramicroporous materials with pillared
inorganic anions (SiF62- = SIFSIX, NbOF52- = NbOFFIVE) can serve as highly
selective C3 H4 traps for the removal of trace C3 H4 from C3 H6 . Especially, it
is revealed that the pyrazine-based ultramicroporous material with square grid
structure for which the pore shape and functional site disposition can be varied
in 0.1-0.5 A scale to match both the shape and interacting sites of guest
molecule is an interesting single-molecule trap for C3 H4 molecule. The pyrazine
based single-molecule trap enables extremely high C3 H4 uptake under ultralow
concentration (2.65 mmol g-1 at 3000 ppm, one C3 H4 per unit cell) and record
selectivity over C3 H6 at 298 K (>250). The single-molecule binding mode for C3
H4 within ultramicroporous material is validated by X-ray diffraction experiments
and modeling studies. The breakthrough experiments confirm that anion-pillared
ultramicroporous materials set new benchmarks for the removal of ultralow
concentration C3 H4 (1000 ppm on SIFSIX-3-Ni, and 10 000 ppm on SIFSIX-2-Cu-i)
from C3 H6 .
PMID- 29345385
TI - Crucial role of Mer tyrosine kinase in the maintenance of SIGN-R1+ marginal zone
macrophages.
AB - Mer Tyrosine Kinase receptor (Mer) is involved in anti-inflammatory
efferocytosis. Here we report elevated spontaneous germinal center (Spt-GC)
responses in Mer-deficient mice (Mer-/- ) that are associated with the loss of
SIGN-R1+ marginal zone macrophages (MZMs). The dissipation of MZMs in Mer-/- mice
occurs independently of reduced cellularity or delocalization of marginal zone B
cells, sinusoidal cells or of CD169+ metallophillic macrophages. We find that MZM
dissipation in Mer-/- mice contributes to apoptotic cell (AC) accumulation in Spt
GCs and dysregulation of the GC checkpoint, allowing an expansion of DNA-reactive
B cells in GCs. We further observe that bone marrow derived macrophages from Mer
/- mice produce more TNFalpha, and are susceptible to cell death upon exposure to
ACs compared to WT macrophages. Anti-TNFalpha Ab treatment of Mer-/- mice is,
however, unable to reverse MZM loss, but results in reduced Spt-GC responses,
indicating that TNFalpha promotes Spt-GC responses in Mer-/- mice. Contrary to an
anti-TNFalpha Ab treatment, treatment of Mer-/- mice with a synthetic agonist for
the transcription factor LXRalpha rescues a significant number of MZMs in vivo.
Our data suggest that Mer-LXRalpha signaling plays an important role in the
differentiation and maintenance of MZMs, which in turn regulate Spt-GC responses
and tolerance.
PMID- 29345386
TI - Quinoline-Flanked Diketopyrrolopyrrole Copolymers Breaking through Electron
Mobility over 6 cm2 V-1 s-1 in Flexible Thin Film Devices.
AB - Herein, the design and synthesis of novel pi-extended quinoline-flanked
diketopyrrolopyrrole (DPP) [abbreviated as QDPP] motifs and corresponding
copolymers named PQDPP-T and PQDPP-2FT for high performing n-type organic field
effect transistors (OFETs) in flexible organic thin film devices are reported.
Serving as DPP-flankers in backbones, quinoline is found to effectively tune
copolymer optoelectric properties. Compared with TDPP and pyridine-flanked DPP
(PyDPP) analogs, widened bandgaps and strengthened electron deficiency are
achieved. Moreover, both hole and electron mobility are improved two orders of
magnitude compared to those of PyDPP analogs (PPyDPP-T and PPyDPP-2FT). Notably,
featuring an all-acceptor-incorporated backbone, PQDPP-2FT exhibits electron
mobility of 6.04 cm2 V-1 s-1 , among the highest value in OFETs fabricated on
flexible substrates to date. Moreover, due to the widened bandgap and
strengthened electron deficiency of PQDPP, n-channel on/off ratio over 105 with
suppressed hole transport is first realized in the ambipolar DPP-based
copolymers.
PMID- 29345387
TI - Fortuitous benefits of living kidney donation: Diagnosis of serious medical
conditions during the living donor evaluation.
AB - BACKGROUND: All living kidney donors are counseled about the possible surgical
and medical risks associated with donation. Only a minority of transplant centers
discuss the potential benefit of discovering undiagnosed medical conditions in
the donor during evaluation, as part of their consent process. METHODS: We
retrospectively investigated all potential living kidney donors evaluated over a
10-year period at a single center to characterize incidentally diagnosed serious
medical conditions. RESULTS: Sixty-five of the 762 potential donors (8.5%) were
not approved for donation because of a newly diagnosed serious medical condition
discovered during their evaluation. This included six patients diagnosed with
malignancies, five of which required operative intervention, six patients
diagnosed with transmittable diseases requiring follow-up and treatment, four
patients were found to have bilateral renal stones with significant stone burden,
and two patients diagnosed with IgA nephropathy. Additionally, four patients were
diagnosed with significant heart disease, and one of those patients subsequently
required a coronary artery bypass surgery. CONCLUSIONS: The evaluation process
can diagnose serious medical conditions in a significant minority of donors that
would have otherwise been unrecognized. The benefit associated with the donor
evaluation should be considered an important part of the consent process.
PMID- 29345388
TI - Dentin bond strength and nanoleakage of the adhesive interface after intracoronal
bleaching.
AB - This study evaluated dentin bond strength (BS) and nanoleakage of non- and pre
etched dentin immediately (T0 ,), 7 days (T7 ), and 14 days (T14 ) after
bleaching. Bovine incisors (150) were selected and half of them submitted to
intrapulpal dentin etching (e). Non- and pre-etched dentin were subjected to the
following (n = 15): no bleaching/control (C); 35% carbamide peroxide (CP); 35%
hydrogen peroxide (35% HP); 25% hydrogen peroxide (25% HP); and sodium perborate
(SP). Bleaching agents were applied to the pulp chamber four times within a 72-h
interval. Afterwards, pulp chamber dentin was prepared for the BS test at
different evaluation times (n = 5): T0 , T7 , and T14 . Composite blocks were
built on pulp chamber and sectioned in slices. Slices were reduced to an hour
glass shape with a cross-sectional area of 0.8 mm2 and submitted to microtensile
BS test. Two additional specimens for each group were prepared for nanoleakage
evaluation by transmission electron microscopy (TEM). Results were analyzed by
ANOVA (two-way) and Dunnett's test (p < .05). BS decreased immediately after
intracoronal bleaching for both sound and pre-etched dentin (p < .05). At T14 ,
the BS of non-etched bleached dentin increased for all groups, whereas the pre
etched SPe group presented BS similar to the Ce. Nanoleakage within the hybrid
layer was perceptible immediately after bleaching, although a decrease in
nanoleakage was observed for all groups at T14 . Adhesive restorations should be
performed 7-14 days after bleaching, according to the bleaching agent used.
Intracoronal bleaching should be performed preferably with sodium perborate if
previous dentin etching is applied.
PMID- 29345389
TI - Percutaneous access to the heart: Nontraditional approaches for the
electrophysiologist.
PMID- 29345390
TI - Frontline Science: Wnt/beta-catenin pathway promotes early engraftment of fetal
hematopoietic stem/progenitor cells.
AB - The switch from fetal to adult hematopoietic stem/progenitor cells (HSPCs) is
associated with profound changes in several genetic programs. Although HSPC
ageing corresponds to alterations in Wnt signaling, relatively little is known
about the relative roles of different Wnt signaling pathways in HSPC ontogeny. We
hypothesized that proliferating fetal HSPCs would be more dependent on canonical
beta-catenin-dependent Wnt signaling when compared to quiescent adult bone marrow
HSPCs. We have compared here Wnt signaling activities in murine fetal and adult
HSPCs and demonstrate a shift from Wnt/beta-catenin-dependent signaling in fetal
liver HSPCs to more predominantly noncanonical Wnt/polarity signaling in adult
HSPCs. beta-Catenin was selectively required for fetal HSPC competitiveness
shortly after transplant, and protected cells from oxidative stress. Our results
emphasize the complexity of Wnt signaling dynamics in HSPC maintenance and
function.
PMID- 29345391
TI - NPTX1 inhibits colon cancer cell proliferation through down-regulating cyclin A2
and CDK2 expression.
AB - Colon cancer is the third most common malignancy and one of the leading causes of
cancer-associated mortality worldwide. Neuronal pentraxin 1 (NPTX1) is associated
with tumor progression in some types of tumors. However, its expression and role
in colon cancer has not been yet reported. Here we observed that NPTX1 was down
regulated in colon cancer. Additionally, we explored the functional significance
of NPTX1 in colon cancer. We found that over-expression of NPTX1 inhibited colon
cancer cell growth by performing MTT, colony formation, Edu corporation assays,
and cell cycle analysis. In vivo mouse experiments also confirmed the anti
proliferative role of NPTX1 in colon cancer. Further mechanistic study showed
that over-expression of NPTX1 inhibited the expression of cyclin A2 and CDK2 in
colon cancer cells, thereby regulating the Rb-E2F signaling. In summary, these
findings reveal that NPTX1 suppress the colon cancer cell growth and might serve
as a useful potential target for treatment of colon cancer.
PMID- 29345392
TI - Who May Benefit From On-Demand Control of Deep Brain Stimulation? Noninvasive
Evaluation of Parkinson Patients.
AB - BACKGROUND: In closed-loop on-demand control (ODC) of deep brain stimulation
(DBS), stimulation is applied only when symptoms appear. Following stimulation of
a fixed duration, DBS is switched off until the symptoms reappear. By repeating
these demand-driven cycles, the amount of stimulation delivered can be decreased,
thereby reducing DBS side-effects and improving battery-life of the pulse
generator. This article introduces Ro metric for quantification of degree of
benefit of ODC and explores candidate selection in tremor-dominant Parkinson's
disease (PD). METHOD: The study was performed on nine PD patients previously
implanted with Medtronic DBS systems. Accelerometer sensor was placed on the
tremor-dominant hand to detect onset of tremor. Fixed duration of stimulation
(DS) of 20-80 sec was applied. Once the tremor was observed, stimulation was
switched on. These trials were repeated during resting, postural, and kinetic
conditions. Ro metric was calculated as the ratio of stimulation-off tremor-free
period to the DS. Ro calculated at different DS were compared for each patient.
RESULTS: We found that for each patient, Ro varied with DS and an optimal DS*
gave a higher percentage of stimulation-off time. Average Ro at DS* varied from
0.554 to 4.24 for eight patients giving 35%-80% stimulation-off time.
CONCLUSIONS: Ro values can be used for selection of optimal DS* in ODC. Three of
nine patients were found to be tremor-free without stimulation for >50% of total
time with even up to 80% in one patient. Patients with low Ro may not benefit
from ODC in DBS, where the trade-off between having side-effects and using ODC
system will need to be assessed.
PMID- 29345393
TI - The Protective Effect of Spinal Cord Stimulation Postconditioning Against Spinal
Cord Ischemia/Reperfusion Injury in Rabbits.
AB - BACKGROUND: Delayed paraplegia due to spinal cord ischemia/reperfusion injury
(IRI) remains one of the most severe complications of thoracoabdominal aneurysm
surgery, for which effective prevention and treatment is still lacking.
OBJECTIVES: The current study investigates whether spinal cord stimulation (SCS)
postconditioning has neuroprotective effects against spinal cord IRI. METHOD:
Ninety-six New Zealand white male rabbits were randomly divided into four groups
as follows: a sham group and three experimental groups (C group, 2 Hz group, and
50 Hz group) n = 24/group. Spinal cord ischemia was induced by transient
infrarenal aortic balloon occlusion for 28 min, after which rabbits in group C
underwent no additional intervention, while rabbits in the other two experimental
groups underwent 2 Hz or 50 Hz epidural SCS for 30 min at the onset of
reperfusion and then daily until sacrifice. Hind limb neurologic function of
rabbits was assessed using Jacob scale. Lumbar spinal cords were harvested
immediately after sacrifice for histological examination and terminal
deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining.
The number of viable alpha-motor neurons in ventral horn was counted and TUNEL
positive rate of alpha-motor neurons was calculated. RESULT: Spinal cord IRI was
caused by transient infrarenal aorta occlusion for 28 min. Both 2 Hz and 50 Hz
SCS postconditioning had neuroprotective effects, particularly the 2 Hz SCS
postconditioning. Comparing to C group and 50 Hz group, rabbits in the 2 Hz group
demonstrated better hind limb motor function and a lower rate of TUNEL-positive
alpha-motor neuron after eight hours, one day, three days, and seven days of
spinal cord reperfusion. More viable alpha-motor neurons were preserved after one
and three days of spinal cord reperfusion in 2 Hz group rabbits than in C group
and 50 Hz group rabbits. CONCLUSION: SCS postconditioning at 2 Hz protected the
spinal cord from IRI.
PMID- 29345394
TI - Viruses as key modulators of the TGF-beta pathway; a double-edged sword involved
in cancer.
AB - Transforming growth factor-beta (TGF-beta) signaling pathway is a key network in
cell signaling that controls vital processes such as proliferation,
differentiation, apoptosis, epithelial-mesenchymal transition, and migration,
thus acting as a double-edged sword in normal development and diseases, in
particular organ fibrosis, vascular disorders, and cancer. Early in
tumorigenesis, the pathway exerts anti-tumor effects through suppressing cell
cycle and inducing apoptosis, while during late stages, it functions as a tumor
promoter by enhancing tumor invasiveness and metastasis. This signaling pathway
can be perturbed by environmental and genetic factors such as microbial
interference and mutation, respectively. In this way, the present review
describes the modulation of the TGF-beta pathway by oncogenic human viral
pathogens and other viruses. The main mechanisms by which viruses interferes with
TGF-beta signaling seems to be through (1) the alteration of either TGF-beta
protein expression or activation, (2) the modulation of the TGF-beta receptors or
SMADs factors (by interfering with their levels and functions), (3) the
alteration of none-SMAD pathways, and (4) indirect interaction with the pathway
by the modulation of transcriptional co-activator/repressor and regulators of the
pathway. Given the axial role of this pathway in tumorigenesis, it can be
regarded as an attractive target for cancer therapy. Hence, further
investigations on this subject may represent molecular targets among either TGF
beta signaling molecules or viral factors for the treatment and management of
viral infection consequences such as cancer.
PMID- 29345395
TI - Patient, carer and public involvement in major system change in acute stroke
services: The construction of value.
AB - BACKGROUND: Patient and public involvement is required where changes to care
provided by the UK National Health Service are proposed. Yet involvement is
characterized by ambiguity about its rationales, methods and impact. AIMS: To
understand how patients and carers were involved in major system changes (MSCs)
to the delivery of acute stroke care in 2 English cities, and what kinds of
effects involvement was thought to produce. METHODS: Analysis of documents from
both MSC projects, and retrospective in-depth interviews with 45 purposively
selected individuals (providers, commissioners, third-sector employees) involved
in the MSC. RESULTS: Involvement was enacted through consultation exercises; lay
membership of governance structures; and elicitation of patient perspectives.
Interviewees' views of involvement in these MSCs varied, reflecting different
views of involvement per se, and of implicit quality criteria. The value of
involvement lay not in its contribution to acute service redesign but in its
facilitation of the changes developed by professionals. We propose 3 conceptual
categories-agitation management, verification and substantiation-to identify
types of process through which involvement was seen to facilitate system change.
DISCUSSION: Involvement was seen to have strategic and intrinsic value. Its
strategic value lay in facilitating the implementation of a model of care that
aimed to deliver evidence-based care to all; its intrinsic value was in the idea
of citizen participation in change processes as an end in its own right. The
concept of value, rather than impact, may provide greater traction in analyses of
contemporary involvement practices.
PMID- 29345396
TI - Performance, rumen fermentation and blood metabolites of dairy calves fed starter
mixtures supplemented with herbal plants, essential oils or monensin.
AB - This study evaluated the supplementation effects of three herbal plants (thyme
[THY], eucalyptus [EUC] and celery [CEL]), a commercial phytogenic additive
containing essential oils (PFA-EO, Digestarom(r) P.E.P.) and monensin (MON) in
calf starter on performance, rumen fermentation and blood metabolites during pre-
(days 3-55) and post-weaning (days 56-70). Sixty-six Holstein dairy calves (3
days of age, 41.2 +/- 3 kg of BW) were allocated to one of six starters
supplemented with: (i) no additives (CON), (ii) MON (30 mg/kg), (iii) THY (23
g/kg), (iv) CEL (23 g/kg), (v) EUC (23 g/kg) and (vi) PFA-EO (3 g/kg). All the
calves were offered starters ad libitum plus 6 L of whole milk daily. Starter
intake tended to be the highest in calves fed PFA-EO and THY; intermediate in
calves fed CON, MON and EUC; and the lowest in those fed CEL. Average daily gain
(ADG) and feed efficiency (FE) remained unaffected by dietary treatments during
the pre-weaning. During the post-weaning period, ADG and FE were greatest in
calves fed EUC followed by those fed CON, MON, PFA-EO and THY, and then in those
fed CEL. No differences were observed among the treatments in skeletal growth,
faecal score, rumen pH or ammonia-N concentration. Compared to calves fed CON and
MON, those fed the herbal plants or PFA-EO tended to recorded higher molar
proportions of acetate and butyrate, and the acetate: propionate ratio. Blood
malondialdehyde level did not differ among treatments, but calves on CON had the
highest glucose concentration, and those fed PFA-EO recorded the highest value
for beta-hydroxyl butyrate on day 70. In conclusion, the results indicate that
the three herbs and PFA-EO are capable of modulating some of the rumen
fermentation parameters and blood metabolites as well as eucalyptus could
potentially be a better alternative to monensin for improving post-weaning
performance.
PMID- 29345397
TI - Characteristics of patients who progress from bridging to long-term oxygen
therapy.
AB - BACKGROUND: Patients with persistent hypoxia following an acute hospital
admission may be discharged with 'bridging' domiciliary oxygen as per criteria
defined by the Thoracic Society of Australia and New Zealand. The need for
continuous long-term oxygen therapy (LTOT) is then reassessed at a clinic review
1-2 months later. AIM: To describe the characteristics of patients discharged
from an acute hospital admission with continuous short-term oxygen therapy
(STOT), and subsequently to investigate for differences between subjects who
proceeded to qualify for continuous LTOT versus those who were able to cease STOT
at review. METHODS: This is a retrospective cohort study involving all subjects
discharged from Alfred Health between 2011 and 2015 inclusive with bridging
domiciliary oxygen. Multiple biochemical, physiological and demographic
characteristics were collated and analysed. RESULTS: Of all patients prescribed
continuous STOT at time of discharge, 47.3% qualified for LTOT at outpatient
review. This cohort had a significantly lower PaO2 measurement at time of
discharge, compared with those who no longer qualified. CONCLUSION: PaO2 at time
of discharge provides a signal with the potential to identify who will require
continuous LTOT following an acute hospital admission. Additionally, this study
highlights the need to re-evaluate patients' oxygen requirements during a period
of clinical stability.
PMID- 29345398
TI - Music reduces state anxiety scores in patients undergoing pleural procedures: a
randomised controlled trial.
AB - BACKGROUND: Patient anxiety is an often overlooked complication of pleural
diagnostic and therapeutic procedures. Listening to music is effective in
reducing patient anxiety in some endoscopy procedures but has not yet been
evaluated in pleural procedures. AIM: To evaluate the benefits of music therapy
during pleural procedures on a patient's anxiety, perceived pain and satisfaction
with the procedure. METHODS: Consecutive patients undergoing therapeutic pleural
procedures were randomised to music and control groups. Participants in the music
group listened to self-selected music using ear-bud headphones for the duration
of the procedure. State anxiety was assessed before and after the procedure using
the State Trait Anxiety Inventory. Physiological parameters were also measured.
RESULTS: Sixty patients were included in the study. In the music group, a
reduction in state anxiety scores were observed post-procedure (34 +/- 11 vs 48
+/- 13, P < 0.001), while no change was observed in the control group (40 +/- 11
vs 42 +/- 11, P = 0.51). Participants in the music group had reductions in heart
rate (87 +/- 17 vs 95 +/- 15, P = 0.04), systolic (121 +/- 13 vs 130 +/- 16, P =
0.02) and diastolic blood pressure (72 +/- 8 vs 78 +/- 9, P = 0.01) post
procedure compared to the pre-procedures values. A similar change was not
detected in the control group: heart rate (86 +/- 17 vs 85 +/- 15, P = 0.73),
systolic (133 +/- 21 vs 134 +/- 20, P = 0.83) and diastolic blood pressure (77 +/
9 vs 79 +/- 10, P = 0.30). There was no difference in patient pain scores (P =
0.8), willingness to undergo the procedure again (P= 0.27), satisfaction with the
performance of the pleural procedure (P = 0.20) and duration of the procedure (P
= 0.68) between the music and control groups. CONCLUSIONS: Listening to music
appears to be beneficial in reducing anxiety in patients undergoing pleural
procedures.
PMID- 29345399
TI - Glycine improves the remodeling process of tenocytes in vitro.
AB - Tendinitis changes the biochemical and morphological properties of the tendon,
promoting an increase of activity of metalloproteinases and disorganization of
collagen bundles. Tenocytes, the primary cells in tendon, are scattered
throughout the collagenic fibers, and are responsible of tendon remodeling and
tissue repair in pathological condition. In vivo, glycine, component of the
typical Gly-X-Y collagen tripeptide, showed beneficial effects in biochemical and
biomechanical properties of Achilles tendon with tendinitis. In this study, we
analyzed the effect of glycine in tenocytes subjected to inflammation. Tenocytes
from Achilles tendon of rats were treated with TNF-alpha (10 ng/mL) with and
without previous treatment with glycine (20 mM). Cell proliferation and migration
were evaluated, as well as the expression of matrix molecules such as
glycosaminoglycans, metalloproteinases (MMPs), TIMPs, and collagen I. Glycine can
revert the inflammation due to the action of TNF-alpha by controlling the MMPs
quantity and activity. These data indicated that the molecules involved to
remodeling process of extracellular matrix are modulated both by TNF-alpha and
the availability of collagen precursors; in fact, this study indicates the
glycine can be useful for treatment of inflammation and for modulating tenocytes
metabolism in tendons.
PMID- 29345400
TI - Fludrocortisone-a treatment for tubulopathy post-paediatric renal
transplantation: A national paediatric nephrology unit experience.
AB - Calcineurin inhibitors post-renal transplantation are recognized to cause
tubulopathies in the form of hyponatremia, hyperkalemia, and acidosis. Sodium
supplementation may be required, increasing medication burden and potentially
resulting in poor compliance. Fludrocortisone has been beneficial in addressing
tubulopathies in adult studies, with limited paediatric data available. A
retrospective review of data from an electronic renal database from December 2014
to January 2016 was carried out. Forty-seven post-transplant patients were
reviewed with 23 (49%) patients on sodium chloride or bicarbonate. Nine patients,
aged 8.3 years (range 4.9-16.4), commenced fludrocortisone 22 months (range 1-80)
after transplant and were followed up for 9 months (range 2-20). All patients
stopped sodium bicarbonate; all had a reduction or no increase in total daily
doses of sodium chloride. Potassium levels were significantly lower on
fludrocortisone, 5.2 vs 4.5 mmol/L, P = .04. No difference was noted in renal
function (eGFR 77.8 vs 81.7 mL/min/1.73 m2 , P = .45) and no significant increase
in systolic blood pressure (z-scores 0.99 vs 0.85, P = .92). No side effects
secondary to treatment with fludrocortisone were reported. A significant
proportion of renal transplant patients were on sodium supplementation and
fludrocortisone reduced sodium supplementation without significant effects on
renal function or blood pressure. Fludrocortisone appears to be safe and
effective for tubulopathies in children post-transplantation.
PMID- 29345401
TI - Are characteristics of abdominal pain helpful to identify patients with visceral
hypersensitivity in irritable bowel syndrome? Results of a prospective study.
AB - BACKGROUND: Some consider that patients with visceral hypersensitivity may
represent a separate entity within the IBS population not only from a
pathophysiological but also from a clinical perspective. The aim of this
prospective exploratory study was to assess whether characteristics of abdominal
pain in IBS patients could be suggestive of hypersensitivity. METHODS: This
prospective study included consecutive IBS patients selected by Rome III
criteria. Validated scores (IBS-SSS, Bristol stool scale, HADS) were used to
phenotype patients who were also asked to describe the main location of their
abdominal pain on a simple image (abdomen divided into 6 zones). Progressive
isobaric rectal distensions were performed to demonstrate, with the ascending
method of limits, allodynia (pain threshold lower than 24 mmHg). KEY RESULTS:
Fifty patients (women: 72%), 42.6 +/- 15.7 years old, were included. Sub-types
were IBS-D, IBS-C and IBS-M in 58%, 22% and 20% of cases, respectively. Allodynia
was present in 18% of cases. Neither IBS-SSS nor intensity of pain was predictive
of hypersensitivity. In hypersensitive patients, pain was more often located in
one of the two iliac fossa (P = 0.02) and located outside these areas in only 11%
of cases. The sensitivity and the specificity of this pain location to
differentiate hyper from normosensitive patients were 0.89 and 0.59,
respectively. CONCLUSIONS & INFERENCES: The location of pain is different between
hyper and normosensitive IBS patients. Pain located outside one of the two iliac
fossa suggests that the patient is normosensitive.
PMID- 29345402
TI - Association of long-term glycaemic control on tear break-up times and dry eye
symptoms in Chinese patients with type 2 diabetes.
AB - IMPORTANCE: Diabetes mellitus is known to be associated with dry eye syndrome
(DES), but the effects of long-term glycaemic control on tear film metrics and
dry eye symptoms are not known in the Chinese population. BACKGROUND: To evaluate
tear film stability and dry eye symptoms and their associations with systemic
risk factors in Chinese patients with type 2 diabetes mellitus (T2DM). DESIGN:
Cross-sectional study set at the Lo Fong Siu Po Eye Centre (Grantham Hospital),
Hong Kong. PARTICIPANTS: A total of 80 Chinese participants, aged 18 or above,
with T2DM recruited from the specialist outpatient setting were included.
METHODS: The Oculus Keratograph 5M (Oculus Inc., Wetzlar, Germany) was used to
measure the non-invasive tear break-up time (NITBUT). Ocular symptoms were
evaluated using the Ocular Surface Disease Index (OSDI). The association between
OSDI, NITBUT and metabolic parameters relating to diabetes were evaluated using
multiple linear regression. MAIN OUTCOME MEASURES: The associations between long
term glycaemic control and NITBUT and OSDI scores. RESULTS: Stepwise multiple
linear regression analysis revealed glycated haemoglobin to be the only
significant independent variable for NITBUT (R2 = 0.099, P = 0.014) and OSDI (R2
= 0.062, P = 0.044) after controlling for potential confounders. The age-adjusted
prevalence of DES was 20% (95% confidence interval: 11-30%) in the Chinese T2DM
population. The odds of DES for increasing percentage of glycated haemoglobin was
1.49 (95% confidence interval: 1.03-2.17, P = 0.04). CONCLUSIONS AND RELEVANCE:
Our findings highlight the importance of good glycaemic control as a modifiable
risk factor for both dry eye symptoms and tear film instability in patients with
T2DM.
PMID- 29345403
TI - Improving patient adherence to secondary prevention medications 6 months after an
acute coronary syndrome: observational cohort study.
AB - BACKGROUND: Most patients are recommended secondary prevention pharmacotherapies
following an acute coronary syndromes (ACS). AIM: To identify predictors of
adherence at 6 months and strategies to improve adherence to these therapies.
METHODS: Patients in the CONCORDANCE registry who were discharged on evidence
based medications were stratified into those receiving >=75% ('adherent') or <75%
('non-adherent') of indicated medications at 6 months. Baseline characteristics,
hospital and post-discharge care were compared between groups. Multivariable
logistic analysis identified independent predictors of adherence. The relative
contribution of each clinical or treatment factor to 'adherence' was determined
using an adequacy measure method. RESULTS: Follow-up data were available for 6595
patients, 4492 (68.1%) of whom were 'adherent'. Clinical factors predictive of
adherence included previous stroke, percutaneous coronary intervention (PCI) and
hypertension (odds ratios (OR) 1.36-1.56); factors predictive of non-adherence
included discharge diagnosis of non-ST-segment elevation myocardial infarction
(vs unstable angina) (OR 0.51) and atrial fibrillation (OR 0.59). Discharge on
>=75% of indicated medications was a strong predictor of adherence at 6 months
(OR 10.23, 95% confidence interval 7.89-13.27); in-hospital management factors
predicting non-adherence were medical management alone (OR 0.34) and coronary
artery bypass graft (OR 0.50) (both vs PCI). Post-discharge predictors of
adherence included cardiac rehabilitation (OR 1.36) and general practitioner
attendance (OR 1.40). CONCLUSION: Failure to discharge patients on indicated
therapies is the most important modifiable predictor of adherence failure 6
months after an ACS. Implementing protocols to automate prescription of indicated
discharge therapies, has the potential to reduce non-adherence dramatically in
the 6 months following discharge.
PMID- 29345404
TI - Individual variability in response to renin angiotensin aldosterone system
inhibition predicts cardiovascular outcome in patients with type 2 diabetes: A
primary care cohort study.
AB - AIMS: To assess variability in systolic blood pressure (SBP) and albuminuria
(urinary albumin creatinine ratio [UACR]) responses in patients with type 2
diabetes mellitus initiating renin angiotensin aldosterone system (RAAS)
inhibition, and to assess the association of response variability with
cardiovascular outcomes. MATERIAL AND METHODS: We performed an observational
cohort study in patients with type 2 diabetes who started RAAS inhibition between
2007 and 2013 (n = 1600). Patients were identified from general practices in the
Netherlands. Individual response in SBP and UACR was assessed during 15 months'
follow-up. Patients were categorized as: good responders (?SBP <0 mm Hg and ?UACR
<0%); intermediate responders (?SBP <0 mm Hg and ?UACR >0% or ?SBP >0 mm Hg and
?UACR <0%); or poor responders (?SBP >0 mm Hg and ?UACR >0%). Multivariable Cox
regression was performed to test the association between initial RAAS inhibition
response and subsequent cardiovascular outcomes. RESULTS: After starting RAAS
inhibition, the mean SBP change was -13.2 mm Hg and the median UACR was -36.6%,
with large between-individual variability, both in SBP [5th to 95th percentile:
48.5-20] and UACR [5th to 95th percentile: -87.6 to 171.4]. In all, 812 patients
(51%) were good responders, 353 (22%) had a good SBP but poor UACR response, 268
(17%) had a good UACR but poor SBP response, and 167 patients (10%) were poor
responders. Good responders had a lower risk of cardiovascular events than poor
responders (hazard ratio 0.51, 95% confidence interval 0.30-0.86; P = .012).
CONCLUSIONS: SBP and UACR response after RAAS inhibition initiation varied
between and within individual patients with type 2 diabetes treated in primary
care. Poor responders had the highest risk of cardiovascular events, therefore,
more efforts are needed to develop personalized treatment plans for these
patients.
PMID- 29345405
TI - Abdominal paracentesis: use of a standardised procedure checklist and equipment
kit improves procedural quality and reduces complications.
AB - BACKGROUND: Paracentesis is a common invasive procedure performed by junior
doctors. Audit of procedure conduct at two New Zealand hospitals in 2012 revealed
poor performance across a range of quality measures, including documentation of
informed consent, excessive catheter dwell times and inappropriate albumin
prescription. Complication rates were 12.7%, compared with published rates of
around 9%. A local procedure protocol did not exist. AIM: To evaluate the effect
of a standardised procedure checklist (PC) and equipment kit (EK) on procedural
quality and complication rates for abdominal paracentesis. METHODS: After
presenting the 2012 audit results to resident doctors, we reviewed the
paracentesis literature and developed a local procedure protocol (PC and EK).
These tools were made readily available after an education campaign. Paracenteses
performed after the intervention were studied to determine the impact on
procedural quality and safety. RESULTS: Seventy-four paracenteses (14 diagnostic;
60 therapeutic) were performed in 10 months after the introduction of PC and EK.
Significant improvements were observed with the use of PC including documentation
of informed consent (97% vs 74%, P = <0.01) and aseptic technique (100% vs 62%, P
= <0.01). Catheter dwell times <6 h improved (72% vs 48%, P = 0.02).
Inappropriate albumin prescriptions were less frequent (21% vs 66%, P = <0.01).
Complication rates decreased from 12.7% to 2.8% (P = <0.01). CONCLUSIONS: The PC
and EK improved rates of informed consent, appropriate documentation and protocol
adherence. Significantly fewer procedure-related complications occurred after
introduction of these tools.
PMID- 29345406
TI - Helicobacter pylori infection and occurrence of celiac disease in subjects HLA
DQ2/DQ8 positive: A prospective study.
AB - BACKGROUND: Celiac disease (CD) occurs in subjects positive for HLA-DQ2 and/or
DQ8 gene loci at any age following ingestion of gluten-containing food. An
increased permeability of the mucosa allows interactions between gliadin
macromolecules and genetic factors. It has been observed that Helicobacter pylori
has the ability to modulate the integrity of the duodenal epithelium. We aimed to
determine whether H. pylori infection may enhance the occurrence of CD in
genetically susceptible subjects. MATERIALS AND METHODS: This was a prospective
observational study. Patients undergoing upper endoscopy for any reason and
positive for HLA-DQ2 and/or DQ8 haplotypes with or without CD were included. H.
pylori infection was defined as a positive gastric histopathology and/or 13C-urea
breath test. Prevalence of infection was compared between enrolled subjects with
and without CD. Multiple logistic regression analysis, adjusting odds ratios for
patient age, gender, smoking habit, residency, body mass index, and assumption of
nonsteroidal anti-inflammatory drugs (NSAIDs) and proton-pump inhibitors (PPIs)
were performed. RESULTS: A total of 397 genetically susceptible individuals (mean
age: 37.7 +/- 15.3 years; 86% women) were enrolled between October 2014 and
October 2017. There were 265 (68%) patients with a diagnosis of CD. Overall, the
prevalence of H. pylori infection was 33% and was similar in patients with and
without CD (32% vs 36%). Adjustment for all covariates did not reveal any
significant association, although adjusted odds ratio (OR) for CD was higher in
female (OR = 1.302), in patients H. pylori positive (OR = 1.277), followed by use
of NSAIDs (OR = 1.126), respectively. The use of PPIs appeared to be mildly
protective against CD (OR = 0.644). CONCLUSION: Our study did not reveal any
significant relationship between H. pylori and CD risk, even taking into account
other confounders. More importantly, our findings do not support a "protective"
role of H. pylori infection against CD, as previously reported. Therefore, there
are no reasons to avoid eradication of H. pylori also in subject genetically
susceptible for CD.
PMID- 29345407
TI - Hepatitis C eradication with DAA and risk of liver cancer recurrence: The debate
unrests.
PMID- 29345408
TI - The effect of eradication of Helicobacter pylori on gastric cancer prevention in
healthy asymptomatic populations.
AB - BACKGROUND: Although many epidemiologic studies have evaluated the effect of
Helicobacter pylori eradication on gastric cancer, the effect is still uncertain
in general populations. We evaluated whether H. pylori eradication would affect
the incidence of gastric cancer in healthy asymptomatic populations. MATERIALS
AND METHODS: We performed a retrospective cohort study in 38 984 asymptomatic
individuals, who underwent health screening examinations more than twice between
2005 and 2016. We investigated the incidence of gastric cancer among 3 groups:
those without H. pylori infection (Hp-negative group), those with H. pylori
eradication (eradication group), and those without H. pylori eradication (non
eradication group). RESULTS: The cumulative incidence of gastric cancer was 54.5
cases per 100 000 person-years during a median of 6.4 years. In a multivariate
analysis using the Cox proportional hazard model, the cumulative incidence of
gastric cancer in the non-eradication group was significantly higher than those
in the Hp-negative (hazard ratio [HR] 4.12, P < .001) and eradication groups (HR
2.73, P = .001). However, the cumulative incidence of gastric cancer was not
significantly different between the eradication and Hp-negative groups. Other
risk factors for gastric cancer occurrence were age, smoking, family history of
gastric cancer, and gastric atrophy. The standardized incidence ratios of the age
groups above 40 and below 70 in the eradication group were all significantly
decreased. CONCLUSIONS: Helicobacter pylori eradication reduced the cumulative
incidence of gastric cancer in healthy asymptomatic population, and the effect of
H. pylori eradication on the prevention of gastric cancer was observed in all
ages.
PMID- 29345409
TI - How I investigate monocytosis.
AB - Monocytosis is a common finding that is caused by a wide variety of neoplastic
and non-neoplastic conditions. The adequate evaluation of monocytosis involves
the integration of laboratory data, morphology, clinical findings, and the
judicious use of ancillary studies. We review the literature on monocytosis,
including the 2017 revised 4th edition of the World Health Organization
classification of hematopoietic neoplasms. We present a review of monocytosis
with practical guidelines on how to approach both routine and challenging cases.
PMID- 29345410
TI - High-Resolution Three-Dimensional Computed Tomography Reconstruction as First
Line Imaging Modality to Detect Intrathecal Catheter Malfunction.
PMID- 29345411
TI - Ethnicity, socioeconomic status and the severity and course of non-cystic
fibrosis bronchiectasis.
AB - BACKGROUND AND AIMS: This study evaluated whether there are ethnic factors which
affect the severity and progression of bronchiectasis in our adult multi-ethnic
population in Auckland, New Zealand. METHODS: Clinical records were reviewed from
patients attending the outpatient facilities of our institution between 2007 and
2010. Data collected included demographics, clinical features, smoking status,
self-reported ethnicity, socioeconomic status (NZDep), pulmonary function and
sputum microbiology. RESULTS: A total of 437 patients was identified: median age
65 years, 66% female, mean forced expiratory volume in the first second (FEV1 )
62.4% predicted, and 10.5% of patients had recurrent growth of Pseudomonas
aeruginosa. Patients of Maori and Pacific ethnicity were overrepresented compared
to the institution population catchment and had more severe impairment of lung
function: mean % predicted FEV1 for Pacific 52.0, Maori 58.6, European 68.6,
Asian 64.2 (P < 0.0001). This was independent of socioeconomic status. However,
no overall decline was seen in serial lung function measurements, either across
the whole cohort or in any particular ethnic group. CONCLUSIONS: Patients of
Maori and Pacific ethnicity are both overrepresented and have more severe
bronchiectasis in this cohort, independent of socioeconomic status. Ethnicity did
not predict decline in pulmonary function. Further studies into genetic
predisposition to bronchiectasis in Maori or Pacific people may be warranted.
PMID- 29345412
TI - WNT5A promotes migration and invasion of human osteosarcoma cells via SRC/ERK/MMP
14 pathway.
AB - WNT5A, a representative ligand of activating several non-canonical WNT signal
pathways, plays significant roles in oncogenesis and tumor inhibition. It has
been shown that the non-receptor tyrosine kinase SRC is required for WNT5A
induced invasion of osteosarcoma cells. However, the precise molecular mechanism
underlying WNT5A/SRC-mediated osteosarcoma cells invasion remains poorly defined.
The study was designed to explore the role of ERK1/2 in WNT5A/SRC-induced
osteosarcoma cells invasion and the downstream target of the SRC/ERK1/2
signalings. We found that WNT5A (100 ng/mL) remarkably stimulated migration and
invasion of human osteosarcoma MG-63 cells, whereas inhibiting either SRC kinase
activity by siRNA-mediated SRC silence or ERK1/2 phosphorylation by PD98059
treatment suppressed these effects, which suggested that the activation of SRC
and ERK1/2 is essential for WNT5A-induced MG-63 cells migration and invasion.
Furthermore, ERK1/2 phosphorylation induced by WNT5A was dramatically blocked by
SRC siRNA. Additionally, our study further demonstrated that MMP-14 was
upregulated after exposure to WNT5A in MG-63 cells, and the increased expression
was blocked by SRC siRNA or PD98059. Collectively, these results indicate that
WNT5A activates SRC/ERK1/2 signal pathway, leading to the upregulation of MMP-14
expression and MG-63 cells migration and invasion.
PMID- 29345413
TI - Hepatitis B screening before rituximab therapy: a multicentre South Australian
study of adherence.
AB - BACKGROUND: International guidelines recommend screening for hepatitis B virus
(HBV) infection prior to administration of rituximab, due to high risk of HBV
reactivation in at-risk patients. AIMS: To determine: (i) adherence to the South
Australian (SA) protocol for HBV screening; (ii) HBV prevalence in patients
receiving rituximab; and (iii) outcomes of patients at risk of HBV reactivation.
METHODS: All patients commenced on rituximab at the six major SA public hospitals
during a 12-month period were included in the study. Adherence was assessed by
documentation of both hepatitis B surface antigen (HBsAg) and hepatitis B core
antibody (HBcAb) prior to initiation of rituximab. Patients were observed for a
minimum of 6 months following rituximab initiation. RESULTS: Four hundred and
thirty eight patients were included in the study. The main indication for
rituximab therapy was haematological malignancy (76.0%). Two hundred and nine
(47.7%) failed to receive appropriate HBV screening, 86 (19.6%) had neither HBsAg
nor HBcAb performed, and 119 (27.2%) had only HBsAg performed. The identified
prevalence of at-risk cases (either HBsAg- or HBcAb-positive) within the study
population was 4.6% (20/438 cases). One case of HBV reactivation was identified,
but none led to acute liver failure, transplantation or death. CONCLUSIONS: Poor
adherence to HBV screening protocols suggests the need for targeted clinician
education and system redesign. While the rate of reactivation was low, the
prevalence of at-risk patients in this population was high and justifies further
initiatives to increase adherence rates to HBV screening pre-rituximab.
PMID- 29345414
TI - Molecular characterization of a series of 990 index patients with albinism.
AB - Albinism is a clinically and genetically heterogeneous disease characterized by
variable degrees of hypopigmentation and by nystagmus, foveal hypoplasia, and
chiasmatic misrouting of the optic nerves. The wide phenotypic heterogeneity
impedes the establishment of phenotype-genotype correlations. To obtain a precise
diagnosis, we screened the 19 known albinism genes in 990 index patients using
targeted next-generation sequencing (NGS) and high-resolution comparative genomic
hybridization. A molecular diagnosis was obtained in 72.32% of patients. A total
of 243 new pathogenic variants were identified. Intragenic rearrangements
represented 10.8% of all pathogenic alleles. NGS panel analysis allowed
establishing a diagnosis for the rarest forms of the disease, which could not be
diagnosed otherwise. Because of the clinical overlap between the different forms
of the disease, diagnosis nowadays clearly relies on molecular grounds.
PMID- 29345415
TI - Investigating Complications Associated With Occipital Nerve Stimulation: A MAUDE
Study.
AB - OBJECTIVES: The objectives of this study are to utilize the MAUDE data base to
enhance our understanding of the complication profile for Occipital Nerve
Stimulation, a therapy for which the current level of evidence is limited.
Additionally, it is our objective to describe a systematic approach to processing
the MAUDE data, which addresses its flaws and enhances its utility. METHODS: From
the FDA website, we accessed adverse events reports from the MAUDE data base for
devices used in Occipital Nerve Stimulation between June 30, 2007 and June 30,
2017. All reports were sorted into an overall classification for types of adverse
events, types of patient complaints, and types of specific device-related
complications. We then evaluated for the total number of adverse event reports
that contained each of the patient complains and device-related complications.
RESULTS: A total of 1233 adverse event records were obtained. Eight hundred
twenty-two records were classified as surgically manageable post-operative
complications, 121 as device malfunction, 29 as patient compliance issues, and 27
as intra-operative complications. Two hundred thirty-seven records were not
classified. A total of 683 records contained patient complaints including 467
complaints of ineffective stimulation, 122 complaints of inappropriate or over
stimulation, 50 complaints of device-shock, and 44 complaints of IPG site pain.
We found 581 post-operative device-related complications, which included 206
instances of lead migration, 157 reports of lead erosion, 155 infections, 46 lead
fractures, and 17 lead disconnections. CONCLUSION: The MAUDE data base is a
useful tool to investigate device related complications and helps fill the
current gap in ONS data. Reviewing the types and frequencies of complications
reported over the years allows clinicians with less personal experience to have a
more realistic expectation of complications and make informed decisions based on
the patient's unique needs. Additionally, patient complaint data are useful in
establishing more realistic expectations for patient outcomes.
PMID- 29345416
TI - A qualitative study: experiences of stigma by people with mental health problems.
AB - OBJECTIVES: Prior research has examined various components involved in the impact
of public and internalized stigma on people with mental health problems. However,
studies have not previously investigated the subjective experiences of mental
health stigma by those affected in a non-statutory treatment-seeking population.
DESIGN: An in-depth qualitative study was conducted using thematic analysis to
investigate the experiences of stigma in people with mental health problems.
METHODS: Eligible participants were recruited through a local mental health
charity in the North West of England. The topic of stigma was examined using two
focus groups of thirteen people with experience of mental health problems and
stigma. RESULTS: Two main themes and five subthemes were identified. Participants
believed that (1) the 'hierarchy of labels' has a profound cyclical impact on
several levels of society: people who experience mental health problems, their
friends and family, and institutional stigma. Furthermore, participants suggested
(2) ways in which they have developed psychological resilience towards mental
health stigma. CONCLUSIONS: It is essential to utilize the views and experiences
gained in this study to aid understanding and, therefore, develop ways to reduce
the negative impact of public and internal stigma. PRACTITIONER POINTS: People
referred to their mental health diagnosis as a label and associated that label
with stigmatizing views. Promote awareness and develop improved strategies (e.g.,
training) to tackle the cyclical impact of the 'hierarchy of labels' on people
with mental health problems, their friends and family, and institutional stigma.
Ensure the implementation of clinical guidelines in providing peer support to
help people to combat feeling stigmatized. Talking about mental health in
psychological therapy or health care professional training helped people to take
control and develop psychological resilience.
PMID- 29345417
TI - Catheter-based edge-to-edge mitral valve repair for pulmonary pressure reduction
and to postpone heart transplantation in a teenaged patient.
AB - We report a case of catheter-based edge-to-edge mitral valve repair in a teenage
male patient with non-ischaemic cardiomyopathy to improve pulmonary hypertension
secondary to severe functional mitral regurgitation (FMR) to defer anticipated
heart transplantation. A 19-year-old patient with previous history of fulminant
myocarditis followed by markedly left ventricular dysfunction presented with
severe mitral regurgitation 3 years after initial recovery. Slightly over time,
deterioration of FMR was associated with gradual increase in pulmonary artery
pressures despite optimal medical therapy. MitraClip implantation in this young
patient was successfully performed with sustainable improvement of pulmonary
hypertension.
PMID- 29345418
TI - Welcome to the New Editorial Board Members.
AB - We warmly welcome our new Editorial Board members Matthias Bickelhaupt, Sally
Brooker, Xiaoming Feng, Mikiko Sodeoka, and Takafumi Ueno.
PMID- 29345419
TI - Targeting the BCL2 Gene Promoter G-Quadruplex with a New Class of
Furopyridazinone-Based Molecules.
AB - Targeting of G-quadruplex-forming DNA in the BCL2 gene promoter to inhibit the
expression of anti-apoptotic Bcl-2 protein is an attractive approach to cancer
treatment. So far, efforts made in the discovery of molecules that are able to
target the BCL2 G-quadruplex have succeeded mainly in the identification of
ligands with poor drug-like properties. Here, a small series of furo[2,3
d]pyridazin-4(5H)-one derivatives were evaluated as a new class of drug-like G
quadruplex-targeting compounds. Biophysical studies showed that two derivatives
could effectively bind to BCL2 G-quadruplex with good selectivity. Moreover, one
such ligand was found to appreciably inhibit BCL2 gene transcription, with a
substantial decrease in protein expression levels, and also showed significant
cytotoxicity toward the Jurkat human T-lymphoblastoid cell line.
PMID- 29345420
TI - Integration of Gas Enhanced Oil Recovery in Multiphase Fermentations for the
Microbial Production of Fuels and Chemicals.
AB - In multiphase fermentations where the product forms a second liquid phase or
where solvents are added for product extraction, turbulent conditions disperse
the oil phase as droplets. Surface-active components (SACs) present in the
fermentation broth can stabilize the product droplets thus forming an emulsion.
Breaking this emulsion increases process complexity and consequently the
production cost. In previous works, it has been proposed to promote
demulsification of oil/supernatant emulsions in an off-line batch bubble column
operating at low gas flow rate. The aim of this study is to test the performance
of this recovery method integrated to a fermentation, allowing for continuous
removal of the oil phase. A 500 mL bubble column is successfully integrated with
a 2 L reactor during 24 h without affecting cell growth or cell viability.
However, higher levels of surfactants and emulsion stability are measured in the
integrated system compared to a base case, reducing its capacity for oil
recovery. This is related to release of SACs due to cellular stress when
circulating through the recovery column. Therefore, it is concluded that the gas
bubble-induced oil recovery method allows for oil separation and cell recycling
without compromising fermentation performance; however, tuning of the column
parameters considering increased levels of SACs due to cellular stress is
required for improving oil recovery.
PMID- 29345421
TI - Synthesis of Histidine-Containing Oligopeptides via Histidine-Promoted Peptide
Ligation.
AB - Histidine-containing peptides are valuable therapeutic agents for a treatment of
neurodegenerative diseases. However, the synthesis of histidine-containing
peptides is not trivial due to the potential of imidazole sidechain of histidine
to act as a nucleophile if unprotected. A peptide ligation method utilizing the
imidazole sidechain of histidine has been developed. The key imidazolate
intermediate that acts as an internal acyl transfer catalyst during ligation is
generated by deprotonation. Transesterification with amino acids or peptides
tethered with C-terminal thioester followed by N->N acyl shifts led to the final
ligated products. A range of histidine-containing dipeptides could be synthesized
in moderate to good yields via this method without protecting the imidazole
sidechain. The protocol was further extended to tripeptide synthesis via a long
range N->N acyl transfer, and tetrapeptide synthesis.
PMID- 29345422
TI - Cantharidic acid induces apoptosis of human leukemic HL-60 cells via c-Jun N
terminal kinase-regulated caspase-8/-9/-3 activation pathway.
AB - Cantharidin, a natural toxin from blister beetles, has shown potent anticancer
activities on many solid tumor cells. Recently, cantharidin and its analogue,
norcantharidin, were also shown to suppress nonsolid tumors such as chronic
myeloid leukemia, acute myeloid leukemia (AML), and leukemic stem cells. However,
there is no available information to address the effects of cantharidic acid
(CAC), a hydrolysis product of cantharidin, on human AML cells. The present study
showed that CAC, at a range of concentrations (0-20 MUM), concentration
dependently inhibited cell proliferation in the HL-60 AML cell line. Western blot
and flow cytometric assays demonstrated that CAC induced several features of
apoptosis such as sub G1-phase cell increase, phosphatidylserine (PS)
externalization, and significantly activated proapoptotic signaling including
caspase-8, -9, and -3 activation and poly(ADP-ribose) polymerase (PARP) cleavage
in HL-60 AML cells. Moreover, treatment of HL-60 cells with CAC induced
concentration- and time- dependent activation of p38 mitogen-activated protein
kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK). Only JNK-, but not p38 MAPK
specific inhibitor can reverse the CAC-induced activation of the caspase-8, -9,
and -3. We concluded that CAC can induce apoptosis in human leukemic HL-60 cells
via a caspases-dependent pathway, and that the apoptosis-inducing effect of CAC
can be regulated by JNK activation signaling.
PMID- 29345423
TI - Deep Eutectic Solvent Aqueous Solutions as Efficient Media for the Solubilization
of Hardwood Xylans.
AB - This work contributes to the development of integrated lignocellulosic-based
biorefineries by the pioneering exploitation of hardwood xylans by solubilization
and extraction in deep eutectic solvents (DES). DES formed by choline chloride
and urea or acetic acid were initially evaluated as solvents for commercial xylan
as a model compound. The effects of temperature, molar ratio, and concentration
of the DES aqueous solutions were evaluated and optimized by using a response
surface methodology. The results obtained demonstrated the potential of these
solvents, with 328.23 g L-1 of xylan solubilization using 66.7 wt % DES in water
at 80 degrees C. Furthermore, xylans could be recovered by precipitation from
the DES aqueous media in yields above 90 %. The detailed characterization of the
xylans recovered after solubilization in aqueous DES demonstrated that 4-O-methyl
groups were eliminated from the 4-O-methylglucuronic acids moieties and uronic
acids (15 %) were cleaved from the xylan backbone during this process. The
similar Mw values of both pristine and recovered xylans confirmed the success of
the reported procedure. DES recovery in four additional extraction cycles was
also demonstrated. Finally, the successful extraction of xylans from Eucalyptus
globulus wood by using aqueous solutions of DES was demonstrated.
PMID- 29345424
TI - A Fluorescence-Based Sensor Assay that Monitors General Protein Aggregation in
Human Cells.
AB - Protein conformational disorders are characterized by disruption of protein
folding and toxic accumulation of protein aggregates. Here we describe a
sensitive and simple method to follow and monitor general protein aggregation in
human cells. Heat shock protein 27 (HSP27) is an oligomeric small heat shock
protein that binds and keeps unfolded proteins in a folding competent state. This
high specificity of HSP27 for aggregated proteins can be explored to monitor
aggregation in living cells by fusing it to a fluorescent protein as Green
Fluorescent Protein (GFP). We have constructed a HeLa stable cell line expressing
a HSP27:GFP chimeric reporter protein and after validation, this stable cell line
is exposed to different agents that interfere with proteostasis, namely Arsenite,
MG132, and Abeta-peptide. Exposure to proteome destabilizers lead to re
localization of HSP27:GFP fluorescence to foci, confirming that our reporter
system is functional and can be used to detect and follow protein aggregation in
living cells. This reporter is a valuable tool to setup wide-genetic screens to
identify genes and pathways involved in protein misfolding and aggregation.
PMID- 29345425
TI - Eligibility of sacubitril-valsartan in a real-world heart failure population: a
community-based single-centre study.
AB - AIMS: This study aims to investigate the eligibility of the Prospective
Comparison of Angiotensin Receptor-Neprilysin Inhibitor (ARNI) with ACE inhibitor
to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM
HF) study to a real-world heart failure population. METHODS AND RESULTS: Medical
records of all heart failure patients living within the catchment area of Umea
University Hospital were reviewed. This district consists of around 150 000
people. Out of 2029 patients with a diagnosis of heart failure, 1924 (95%) had at
least one echocardiography performed, and 401 patients had an ejection fraction
of <=35% at their latest examination. The major PARADIGM-HF criteria were
applied, and 95 patients fulfilled all enrolment criteria and thus were eligible
for sacubitril-valsartan. This corresponds to 5% of the overall heart failure
population and 24% of the population with ejection fraction <= 35%. The eligible
patients were significantly older (73.2 +/- 10.3 vs. 63.8 +/- 11.5 years), had
higher blood pressure (128 +/- 17 vs. 122 +/- 15 mmHg), had higher heart rate (77
+/- 17 vs. 72 +/- 12 b.p.m.), and had more atrial fibrillation (51.6% vs. 36.2%)
than did the PARADIGM-HF population. CONCLUSIONS: Only 24% of our real-world
heart failure and reduced ejection fraction population was eligible for
sacubitril-valsartan, and the real-world heart failure and reduced ejection
fraction patients were significantly older than the PARADIGM-HF population. The
lack of data on a majority of the patients that we see in clinical practice is a
real problem, and we are limited to extrapolation of results on a slightly
different population. This is difficult to address, but perhaps registry-based
randomized clinical trials will help to solve this issue.
PMID- 29345426
TI - Single-dose intravenous iron in Southeast Asian heart failure patients: A pilot
randomized placebo-controlled study (PRACTICE-ASIA-HF).
AB - AIMS: Iron deficiency is highly prevalent in Southeast Asians with heart failure
(HF) and associated with worse outcomes. This trial aimed to assess the effect of
intravenous iron in Southeast Asians hospitalized with decompensated HF. METHODS
AND RESULTS: Fifty patients hospitalized for acute decompensated HF, regardless
of ejection fraction, with iron deficiency (defined as serum ferritin <300 ng/mL
if transferrin saturation is <20%) were randomized to receive either one dose of
intravenous ferric carboxymaltose (FCM) 1000 mg or placebo (0.9% saline)
following HF stabilization and before discharge in two Singapore tertiary
centres. The primary endpoint was difference in 6-min walk test (6MWT) distance
over 12 weeks, while secondary endpoints were quality of life assessed using
validated Kansas City Cardiomyopathy Questionnaire (KCCQ) and Visual Analogue
Scale (VAS). Improvement in 6MWT distance at Week 12 was observed in both FCM and
placebo groups (from 252 +/- 123 to 334 +/- 128 m and from 243 +/- 67 to 301 +/-
83 m, respectively). Unadjusted analysis showed 6MWT distance for FCM exceeded
that for placebo, but adjustment for baseline covariates and time attenuated this
effect {adjusted mean difference between groups: 0.88 m [95% confidence interval
(CI) -30.2 to 32.0, P = 0.956]}. KCCQ overall summary and VAS were similar in
both groups [adjusted mean difference: KCCQ -1.48 (95% CI -8.27 to 5.31, P =
0.670) and VAS 0.26 (95% CI -0.33 to 0.86, P = 0.386)]. FCM was well tolerated
with no serious treatment-related adverse events. CONCLUSIONS: Intravenous FCM
administered pre-discharge in Southeast Asians hospitalized with decompensated HF
is clinically feasible. Changes in 6MWT distance should be measured beyond Week
12 to account for background therapy effects.
PMID- 29345427
TI - Review article: Best practice management of common shoulder injuries and
conditions in the emergency department (part 4 of the musculoskeletal injuries
rapid review series).
AB - Shoulder injuries are a commonly presenting complaint to the ED. In the absence
of an obvious deformity, they can be difficult to assess and definitively
diagnose because of the multiple structures that cause shoulder pain, the acuity
and severity of pain and the lack of range of motion in the ED setting. The
quality of ED care provided to patients with musculoskeletal shoulder pain is
crucial to ensure the best possible outcomes for the patient. This rapid review
investigated best practice for the assessment and management of common shoulder
injuries and conditions in the ED. Databases were searched in 2017, including
PubMed, CINAHL, EMBASE, TRIP and the grey literature, including relevant
organisational websites. Primary studies, systematic reviews and guidelines
published in English-language in the past 12 years that addressed the acute
assessment, management, follow-up plan or prognosis were considered for
inclusion. Data extraction of included articles was conducted, followed by
quality appraisal to rate the level of evidence. The search revealed 1902
articles, of which 73 were included in the review (n = 12 primary articles, n =
49 systematic reviews and n = 12 guidelines). This rapid review provides
clinicians who manage shoulder dislocations, fractures and soft tissue injuries
in the ED a summary of the best available evidence to enhance the quality of care
for optimal patient outcomes. There is strong evidence to support taking a
thorough history and physical examination, with cautious use of special tests
because of their poor diagnostic accuracy. Key points regarding the diagnosis and
management of these injuries are provided.
PMID- 29345428
TI - TRAF3 regulation of inhibitory signaling pathways in B and T lymphocytes by
kinase and phosphatase localization.
AB - This brief review presents current understanding of how the signaling adapter
protein TRAF3 can both induce and block inhibitory signaling pathways in B and T
lymphocytes, via association with kinases and phosphatases, and subsequent
regulation of their localization within the cell. In B lymphocytes, signaling
through the interleukin 6 receptor (IL-6R) induces association of TRAF3 with IL
6R-associated JAK1, to which TRAF3 recruits the phosphatase PTPN22 (protein
tyrosine phosphatase number 22) to dephosphorylate JAK1 and STAT3, inhibiting IL
6R signaling. An important biological consequence of this inhibition is
restraining the size of the plasma cell compartment, as their differentiation is
IL-6 dependent. Similarly, in T lymphocytes, interleukin 2 receptor (IL-2R)
signaling recruits TRAF3, which in turn recruits the phosphatase TCPTP (T cell
protein tyrosine phosphatase) to dephosphorylate JAK3. The resulting inhibition
of IL-2R signaling limits the IL-2-dependent size of the T regulatory cell (Treg)
compartment. TRAF3 also inhibits type 1 IFN receptor (IFNalphaR) signaling to T
cells by this mechanism, restraining expression of IFN-stimulated gene
expression. In contrast, TRAF3 association with two inhibitors of TCR signaling,
C-terminal Src kinase (Csk) and PTPN22, promotes their localization to the
cytoplasm, away from the membrane TCR complex. TRAF3 thus enhances TCR signaling
and downstream T cell activation. Implications are discussed for these regulatory
roles of TRAF3 in lymphocytes, as well as potential future directions.
PMID- 29345429
TI - Engineering 3D Hydrogels for Personalized In Vitro Human Tissue Models.
AB - There is a growing interest in engineering hydrogels for 3D tissue and disease
models. The major motivation is to better mimic the physiological
microenvironment of the disease and human condition. 3D tissue models derived
from patients' own cells can potentially revolutionize the way treatment and
diagnostic alternatives are developed. This requires development of tissue
mimetic hydrogels with user defined and tunable properties. In this review
article, a recent summary of 3D hydrogel platforms for in vitro tissue and
disease modeling is given. Hydrogel design considerations and available hydrogel
systems are summarized, followed by the types of currently available hydrogel
models, such as bulk hydrogels, porous scaffolds, fibrous scaffolds, hydrogel
microspheres, hydrogel sandwich systems, microwells, and 3D bioprinted
constructs. Although hydrogels are utilized for a wide range of tissue models,
this article focuses on liver and cancer models. This article also provides a
detailed section on current challenges and future perspectives of hydrogel-based
tissue models.
PMID- 29345430
TI - Wearable Wireless Tyrosinase Bandage and Microneedle Sensors: Toward Melanoma
Screening.
AB - Wearable bendable bandage-based sensor and a minimally invasive microneedle
biosensor are described toward rapid screening of skin melanoma. These wearable
electrochemical sensors are capable of detecting the presence of the tyrosinase
(TYR) enzyme cancer biomarker in the presence of its catechol substrate,
immobilized on the transducer surface. In the presence of the surface TYR
biomarker, the immobilized catechol is rapidly converted to benzoquinone that is
detected amperometrically, with a current signal proportional to the TYR level.
The flexible epidermal bandage sensor relies on printing stress-enduring inks
which display good resiliency against mechanical deformations, whereas the hollow
microneedle device is filled with catechol-coated carbon paste for assessing
tissue TYR levels. The bandage sensor can thus be used directly on the skin
whereas microneedle device can reach melanoma tissues under the skin. Both
wearable sensors are interfaced to an ultralight flexible electronic board, which
transmits data wirelessly to a mobile device. The analytical performance of the
resulting bandage and microneedle sensing systems are evaluated using TYR
containing agarose phantom gel and porcine skin. The new integrated conformal
portable sensing platforms hold considerable promise for decentralized melanoma
screening, and can be extended to the screening of other key biomarkers in skin
moles.
PMID- 29345432
TI - Getting published.
PMID- 29345431
TI - The effect of diuresis on extravascular lung water and pulmonary function in
acute decompensated heart failure.
AB - AIMS: The effect of extravascular lung water (EVLW) and relationship to
functional status as a result of acute decompensated heart failure (ADHF) are not
well understood. We sought to quantify changes in clinical variables, EVLW,
airway anatomy, spirometry, and diffusing capacity for carbon monoxide before and
after treatment for ADHF. METHODS AND RESULTS: Fifteen patients were recruited
within 24 h of hospital admission. Spirometry, diffusing capacity for carbon
monoxide, and surrogates of EVLW by computed tomography were measured and were
then repeated within 24 h of discharge. From the computed tomography (CT) scan,
surrogates of EVLW were calculated from the distribution of CT attenuation of the
lung tissue. Airways were segmented using the VIDA Apollo software. Patients were
hospitalized for 4.6 +/- 2.1 days, had 10 +/- 4.8 L of fluid removed (7.0 +/- 4.2
L between study visits), and lost 7.1 +/- 4.9 kg. Patients had significant
clearance of fluid from the lungs (per cent change: mean, 4.2 +/- 6.1%; skew,
17.5 +/- 27.0%; kurtosis, 37.6 +/- 56.7%; full-width half-maximum, 10.2 +/-
13.5%). Static lung volumes and maximal flows improved significantly (per cent
change: forced vital capacity, 14.5 +/- 13.6%; forced expiratory volume in 1 s,
15.9 +/- 14.0%; forced expiratory flow at 25-75% of forced vital capacity, 27.2
+/- 42.9%). The ratio of membrane conductance to capillary blood volume improved
significantly (per cent change: alveolar-capillary membrane conductance/capillary
blood volume, 23.4 +/- 22.8%). Weight loss during hospitalization was
significantly correlated with improved spirometry and diffusing capacity.
CONCLUSIONS: Extravascular lung water contributes to the pulmonary congestive
syndrome in ADHF patients, and its clearance is an important component of the
improvement in pulmonary function as a result of inpatient treatment.
PMID- 29345433
TI - Phenotype and Function of Somatic Primary Afferent Nociceptive Neurones with C-,
Adelta- or Aalpha/beta-Fibres.
AB - Nociceptive dorsal root ganglion (DRG) neurones have fibres that conduct in the
C, Adelta and Aalpha/beta conduction velocity range. The properties of
nociceptive compared with non-nociceptive somatic afferent dorsal root ganglion
neurones appear to fall into two patterns, A and B. Pattern A properties of
nociceptive neurones, the more common type, include longer action potential
duration and slower maximum rate of fibre firing, as well as a greater expression
of substance P and calcitonin gene-related peptide immunoreactivity. The values
of pattern A properties appear to be graded according to the conduction velocity
group (C, Adelta or Aalpha/beta) of the fibres. The most pronounced forms of A
type properties are expressed by nociceptive neurones with C-fibres, and these
become less pronounced in nociceptive neurones with Adelta-fibres and least
pronounced in those with Aalpha/beta fibres (C > Adelta > Aalpha/beta). Some of
these properties are also expressed in a less extreme but similarly graded manner
through C, Adelta and Aalpha/beta groups of non-nociceptive low threshold
mechanoreceptive (LTM) neurone. The less common pattern B properties of
nociceptive neurones have similar values in C-, Adelta- and Aalpha/beta-fibre
nociceptive neurones but these clearly differ from LTM units with C-, Adelta- and
Aalpha/beta-fibre conduction velocities. These features of nociceptive neurones
include consistently larger action potential overshoots and longer after
hyperpolarisation durations in nociceptive than in LTM neurones.
PMID- 29345434
TI - Two-Photon-Excited Silica and Organosilica Nanoparticles for Spatiotemporal
Cancer Treatment.
AB - Coherent two-photon-excited (TPE) therapy in the near-infrared (NIR) provides
safer cancer treatments than current therapies lacking spatial and temporal
selectivities because it is characterized by a 3D spatial resolution of 1 um3 and
very low scattering. In this review, the principle of TPE and its significance in
combination with organosilica nanoparticles (NPs) are introduced and then studies
involving the design of pioneering TPE-NIR organosilica nanomaterials are
discussed for bioimaging, drug delivery, and photodynamic therapy. Organosilica
nanoparticles and their rich and well-established chemistry, tunable composition,
porosity, size, and morphology provide ideal platforms for minimal side-effect
therapies via TPE-NIR. Mesoporous silica and organosilica nanoparticles endowed
with high surface areas can be functionalized to carry hydrophobic and
biologically unstable two-photon absorbers for drug delivery and diagnosis.
Currently, most light-actuated clinical therapeutic applications with NPs involve
photodynamic therapy by singlet oxygen generation, but low photosensitizing
efficiencies, tumor resistance, and lack of spatial resolution limit their
applicability. On the contrary, higher photosensitizing yields, versatile
therapies, and a unique spatial resolution are available with engineered two
photon-sensitive organosilica particles that selectively impact tumors while
healthy tissues remain untouched. Patients suffering pathologies such as
retinoblastoma, breast, and skin cancers will greatly benefit from TPE-NIR
ultrasensitive diagnosis and therapy.
PMID- 29345435
TI - N-Modified NiO Surface for Superior Alkaline Hydrogen Evolution.
AB - Boosting the sluggish kinetics of the hydrogen evolution reaction in alkaline
environments is key for the large-scale application of water-alkali and chlor
alkali electrolysis. In this study, nitrogen atoms are used to precisely modulate
electrochemical active sites on the surface of nickel oxide with low-coordinated
oxygen atoms, to achieve enhanced kinetics in alkaline hydrogen evolution.
Theoretical and experimental results demonstrate that surface charge
redistribution after modulation facilitates both the initial water dissociation
step and the subsequent recombination of Had from low-coordinated oxygen sites
and desorption of OHad- from nickel sites, thus accelerating the overall hydrogen
evolution process. The N-modulated nickel oxide enriched in low-coordinated
oxygen atoms exhibits significantly enhanced activity with a small overpotential
of -100 mV at the current density of -10 mA cm-2 and a robust stability over 90 h
for hydrogen evolution in 1.0 m KOH.
PMID- 29345436
TI - Effect of ginseng therapy on diabetes and its chronic complications: lessons
learned.
AB - Ginseng played a significant role in the management of diabetes in China and in
other Asian countries for a long period of time. It has a large number of
pharmacological properties and is relatively free from adverse effects. As a part
of Ontario Ginseng Research and Innovation Consortium, we investigated the
effects of ginseng extract on diabetes and its complications. We demonstrated
large number of beneficial effects of ginseng therapy and showed that these
effects are possibly mediated through its antioxidant properties. Thus ginseng
may lend itself as a relatively safe and inexpensive adjuvant treatment for
diabetes and chronic diabetic complications.
PMID- 29345437
TI - Antioxidant and acetylcholinesterase inhibitory activities of ginger root
(Zingiber officinale Roscoe) extract.
AB - Background Zingiber officinale Roscoe has been used in traditional medicine for
the treatment of neurological disorder. This study aimed to investigate the
phenolic contents, antioxidant, acetylcholinesterase enzyme (AChE) inhibitory
activities of different fraction of Z. officinale root grown in Vietnam. Methods
The roots of Z. officinale are extracted with ethanol 96 % and fractionated with
n-hexane, ethyl acetate (EtOAc) and butanol (BuOH) solvents. These fractions
evaluated the antioxidant activity by 1,1-Diphenyl -2-picrylhydrazyl (DPPH) assay
and AChE inhibitory activity by Ellman's colorimetric method. Results Our data
showed that the total phenolic content of EtOAc fraction was highest equivalents
to 35.2+/-1.4 mg quercetin/g of fraction. Our data also demonstrated that EtOAc
fraction had the strongest antioxidant activity with IC50 was 8.89+/-1.37 ug/mL
and AChE inhibitory activity with an IC50 value of 22.85+/-2.37 MUg/mL in a dose
dependent manner, followed by BuOH fraction and the n-hexane fraction is the
weakest. Detailed kinetic analysis indicated that EtOAc fraction was mixed
inhibition type with Ki (representing the affinity of the enzyme and inhibitor)
was 30.61+/-1.43 ug/mL. Conclusions Our results suggest that the EtOAc fraction
of Z. officinale may be a promising source of AChE inhibitors for Alzheimer's
disease.
PMID- 29345438
TI - Evaluation of hepatic glycogen content, some haematological and biochemical
parameters of alloxan-induced diabetic rats treated with combinations of
glibenclamide and G. latifolium extract.
AB - Background Diabetes is associated with both biochemical and haematological
complications. Combination therapy has been advocated to mitigate some of these
complications. Aim This study was designed to investigate the effects of
glibenclamide and Gongronema latifolium (GL) on hepatic glycogen content and
haemato-biochemical parameters. Methods Thirty male Wistar rats were assigned
into five groups of six rats each. Groups 2-5 rats received intraperitoneally,
160 mg/kg of alloxan monohydrate while group 1 rats served as normal control.
Groups 2-5 rats were respectively treated with 10 mL/kg distilled water (DW), 2
mg/kg glibenclamide, 200 mg/kg GL and 2 mg/kg glibenclamide and 200 mg/kg GL,
while group 1 rats received 10 mL/kg DW. All treatments were per os daily for 21
days. Blood samples for investigation of haemato-biochemical (red blood cell
[RBC], packed cell volume [PCV], haemoglobin concentration [Hb], blood urea
nitrogen [BUN] and creatinine) parameters were collected on days 7, 14 and 21
post-treatment (PT), while the liver sample for hepatic glycogen determination
was obtained on day 21 PT. Results Creatinine and BUN values of groups 3 and 4
rats were comparable to that of group 1 but were significantly (p<0.05) lower
when compared with those of groups 2 and 5. There were significant (p<0.05)
increases in the mean hepatic glycogen content, RBC, PCV, and Hb of group 4 rats
when compared to those of group 2. Conclusions It was concluded that a
combination of glibenclamide and G. latifolium in treatment of diabetic rats
improved glycogen storage and demonstrated beneficial effects on haematology and
kidney marker parameters.
PMID- 29345439
TI - Bivalirudin versus Heparin Monotherapy in Myocardial Infarction.
PMID- 29345440
TI - Bivalirudin versus Heparin Monotherapy in Myocardial Infarction.
PMID- 29345441
TI - Bivalirudin versus Heparin Monotherapy in Myocardial Infarction.
PMID- 29345442
TI - Lung uptake of fluorine-18 fluoroethyl-choline PET-CT in patients with prostate
cancer.
AB - BACKGROUND: Metastatic spreading to the lungs is a negative prognostic factor in
patients with prostate cancer (PC). Aim of our study was to assess the prevalence
of lung PC metastases in patients with fluorine-18 fluoroethyl-choline (F-18
FECh) PET-CT positive lung lesions and the role of Gleason Score (GS) and common
biochemical markers in predicting metastatic spreading to the lungs. METHODS: We
retrospectively evaluated the scans of 1283 patients ongoing (F-18-FECh) PET-CT
for PC between May 2010 and July 2014. Patients with lung lesion with F-18-FECh
uptake were included. Data concerning GS at diagnosis, "trigger" prostate
specific antigen (PSAtr), PSA doubling time (PSAdt), PSA velocity (PSAvel) and
ongoing androgen deprivation therapy were collected. PET-CT findings were
confirmed by histology or followup (FU) and classified as follows: inflammation,
primary lung cancer or metastases from tumour other than PC, and lung metastases
from PC. RESULTS: Twenty-two patients with F-18-FECh positive lung lesion and
available histology or FU were identified. PSAdt was significantly (p=0.029)
shorter in patients with lung metastases from PC (median PSAdt 1.7 months,
interquartile range [IQR] 1.5-4.1 months) than in patients without lung PC
relapse (median PSAdt 6.7 months, IQR 3.9-7.8); PSAvel was significantly
(p=0.019) higher in patients with lung metastases from PC (median PSAvel 3.2
ng/ml/month, IQR 0.65-6.65 ng/ml/month) than in patients without lung PCrelapse
(median PSAvel 0.3 ng/ml/month, IQR 0.2-0.5 ng/ml/month). Patients with lung
metastases from PC had significantly (p=0.006) higher GS at diagnosis (median GS
8) than the other ones (median GS 7). CONCLUSIONS: Our analysis shows that the
prevalence of F-18-FECh positive lung metastases in patients with PC, especially
with higher GS at diagnosis, is higher in presence of a steady increase in PSA
values, confirmed by higher PSAvel and shorter PSAdt.
PMID- 29345443
TI - SUV calculation in breast cancer: which normalization should be applied when
using 18F-FDG PET?
AB - BACKGROUND: When using 18F-FDG PET, glucose metabolism quantification is affected
by various factors. We aimed to investigate the benefit of different SUV
normalizations to improve the accuracy of 18F-FDG uptake to predict breast cancer
aggressiveness and response to treatment. METHODS: Two hundred fifty-two women
with locally advanced breast cancer treated with neoadjuvant chemotherapy (NAC)
were included. Women underwent 18F-FDG PET before and after the first course of
NAC. Glucose serum levels, patient heights and weights were recorded at the time
of each PET exam. Four different procedures for SUV normalization of the primary
tumor were used: by body weight (SUVBW by blood glucose level ( SUVG, by lean
body mass (SUL) and then corrected for both lean body mass and blood glucose
level ( SULG). RESULTS: At baseline, SUL was significantly lower than SUVBW
(5.9+/-4.0 and 9.5+/-6.5, respectively; p<1.10-4), whereas SUVG and SUVBW were
not significantly different (9.7+/-6.4 and 9.5+/-6.5, respectively; P=0.67).
Concerning SUV changes (DeltaSUV), the different normalizations methods did not
induce significant quantitative differences. The correlation coefficients were
high between the four normalizations methods of SUV1, SUV2 and DeltaSUVB (R>0.95;
p<1.10-4). High baseline SUVBW measures were positively correlated with the
biological tumor characteristics of aggressiveness and proliferation (p<1.10-3):
ductal carcinoma, high tumor grading, high mitotic activity, negative estrogen
receptor status and the TNBC subtype. DeltaSUVBW was highly predictive of pCR
(AUC=0.76 on ROC curve analysis; p<1.10-4). The different SUV normalizations
yields identical statistical results and AUC to predict tumor biological
aggressiveness and response to therapy. CONCLUSIONS: In the present setting,
SUVBW and SUL can be considered as robust measures and be used in future
multicentre trials. The additional normalization of SUV by glycemia involves
stringent methodologic procedures to avoid biased risk measurements and offers no
statistical advantages.
PMID- 29345444
TI - Bivalirudin versus Heparin Monotherapy in Myocardial Infarction.
PMID- 29345445
TI - The impact of high progesterone levels on the day of HCG administration in
assisted human reproduction treatments.
AB - OBJECTIVE: Progesterone is a steroid hormone that acts on the endometrium. It is
known for producing physical and mood-related side effects. Few studies have
looked into how progesterone levels affect embryo development and quality. This
study aimed to find a cutoff level for serum progesterone on the day of HCG
administration from which embryo quality is impaired. METHODS: The study included
145 cycles, from which 885 oocytes and 613 embryos were obtained. All patients
had their serum progesterone levels measured on the day of HCG administration.
Data sets were collected from patient medical records. The chi-square test was
used to assess qualitative variables and the Mann-Whitney test to evaluate
quantitative variables. RESULTS: Statistical analysis revealed that serum
progesterone levels and reproductive variables were not significantly associated.
In regards to oocyte maturity, however, when progesterone levels were greater
than 1.3 ng/mL the probability of oocytes being immature increased by 12.7%. The
fragmentation rate of embryos categorized as "top quality" in D3 increased
proportionately to increases in progesterone levels (12.23%). CONCLUSION: High
progesterone levels appeared to be correlated with increased embryo fragmentation
rates, but high serum levels of the hormone on the day of HCG administration had
no impact on reproductive variables and were not associated with impaired embryo
development.
PMID- 29345446
TI - The first South American case of pre-implantation genetic diagnosis to select
compatible embryo for cord blood transplantation as treatment for sickle cell
anemia.
AB - Sickle cell anemia is an inherited systemic hemoglobinopathy that affects
hemoglobin production in red blood cells, leading to early morbidity and
mortality. It is caused by a homozygous nucleotide substitution (c.20A>T) in the
beta-globin gene (HBB) that changes a glutamic acid to a valine in the protein.
We present a case report of a fertile couple, both carriers of the sickle cell
anemia mutation, with one affected daughter. Six cycles of assisted reproductive
techniques were performed, resulting in 53 embryos in cleavage stage. Each embryo
was biopsied and analyzed for pre-implantation genetic diagnosis (PGD) by
fluorescent polymerase chain reaction, using polymorphic markers of the region of
interest followed by capillary electrophoresis in an automated genetic analyzer.
HLA Compatible and normal embryos for the mutation represented 3 (5.66%); while
the carriers and compatible 6 (11.32%); therefore, embryos matching those of the
affected daughter represented 9 (16.98%). A selected embryo in blastocyst stage
was transferred, resulting in a healthy male newborn, who had the umbilical cord
blood cells collected and stored. The affected daughter was immunosuppressed and
received transplanted cells from the umbilical cord blood of her brother; the
treatment was successful. Embryo selection using PGD technologies represent the
most effective treatment plan for parents who want to have a healthy child, and
it could cure another child already affected by inherited hemoglobinopathy.
PMID- 29345447
TI - Evaluation and Management of Lower-Extremity Ulcers.
PMID- 29345448
TI - Evaluation and Management of Lower-Extremity Ulcers.
PMID- 29345449
TI - Evaluation and Management of Lower-Extremity Ulcers.
PMID- 29345450
TI - Noninferiority Trials.
PMID- 29345451
TI - Gadolinium-Loaded Solid Lipid Nanoparticles as a Tumor-Absorbable Contrast Agent
for Early Diagnosis of Colorectal Tumors Using Magnetic Resonance Colonography.
AB - Magnetic resonance (MR) contrast agents focusing on special functions are
required to improve cancer diagnosis, particularly in the early stages. Here, we
designed multifunctional solid lipid nanoparticles (SLNs) with simultaneous
loading of gadolinium (Gd) diethylenetriaminepentaacetic acid (Gd-DTPA) and
octadecylamine fluorescein isothiocyanate (FITC) to obtain Gd-FITC-SLNs as a
tumor-absorbable nanoparticle contrast agent for the histological confirmation of
MR imaging (MRI) findings. Colorectal tumors were evaluated in vitro and in vivo
via direct uptake of this contrast agent, which displayed reasonable T1
relaxivity and no significant cytotoxicity at the experimental concentrations in
human colon carcinoma cells (HT29) and mouse colon carcinoma cells (CT26). In
vitro cell uptake experiments demonstrated that contrast agent absorption by the
two types of cancer cells was concentration-dependent in the safe concentration
range. During in vivo MRI, transrectal infusion of Gd-FITC-SLNs showed more
significant enhancement at the tumor site compared with the infusion of Gd-DTPA
in female C57/BL mice with azoxymethane/dextran sulfate sodium-induced colorectal
highgrade intraepithelial neoplasia. Subsequent confocal fluorescence microscopy
demonstrated Gd-FITC-SLNs as highly concentrated green fluorescent spots
distributed from the tumor capsule into the tumor. This study establishes the
"proof-of-principle" of a new MRI technique wherein colorectal tumors are
enhanced via direct absorption or uptake of the nanoparticle contrast agent.
PMID- 29345452
TI - Noninferiority Trials.
PMID- 29345453
TI - Poly(glycidol) Coating on Ultrahigh Molecular Weight Polyethylene for Reduced
Biofilm Growth.
AB - Semibranched poly(glycidol) (PG-OH) and poly(glycidol allylglycidyl ether) (PG
Allyl) coatings were formed on ultrahigh molecular weight polyethylene (UMWPE) in
a unique two-step process which included radiation of UHMWPE followed by grafting
of PG-OH or PG-Allyl to the surface via free radical cross-linking. Resulting
surfaces were extensively characterized by FTIR-ATR, XPS, fluorescent microscopy,
and contact goniometry. The performance was evaluated using the most prominent
biofilm-forming bacteria Staphylococcus aureus for 24 and 48 h. The PG-Allyl
coating demonstrated a 3 log reduction in biofilm growth compared to noncoated
control, demonstrating a promising potential to inhibit adherence and
colonization of biofilm-forming bacteria that often develop into persistent
infections.
PMID- 29345454
TI - Stability and Performance of CsPbI2Br Thin Films and Solar Cell Devices.
AB - In this manuscript, the inorganic perovskite CsPbI2Br is investigated as a
photovoltaic material that offers higher stability than the organic-inorganic
hybrid perovskite materials. It is demonstrated that CsPbI2Br does not
irreversibly degrade to its component salts as in the case of methylammonium lead
iodide but instead is induced (by water vapor) to transform from its metastable
brown cubic (1.92 eV band gap) phase to a yellow phase having a higher band gap
(2.85 eV). This is easily reversed by heating to 350 degrees C in a dry
environment. Similarly, exposure of unencapsulated photovoltaic devices to water
vapor causes current (JSC) loss as the absorber transforms to its more
transparent (yellow) form, but this is also reversible by moderate heating, with
over 100% recovery of the original device performance. NMR and thermal analysis
show that the high band gap yellow phase does not contain detectable levels of
water, implying that water induces the transformation but is not incorporated as
a major component. Performances of devices with best efficiencies of 9.08% (VOC =
1.05 V, JSC = 12.7 mA cm-2 and FF = 68.4%) using a device structure comprising
glass/ITO/c-TiO2/CsPbI2Br/Spiro-OMeTAD/Au are presented, and further results
demonstrating the dependence of the performance on the preparation temperature of
the solution processed CsPbI2Br films are shown. We conclude that encapsulation
of CsPbI2Br to exclude water vapor should be sufficient to stabilize the cubic
brown phase, making the material of interest for use in practical PV devices.
PMID- 29345455
TI - Three-Dimensional Printing of Bisphenol A-Free Polycarbonates.
AB - Polycarbonates are widely used in food packages, drink bottles, and various
healthcare products such as dental sealants and tooth coatings. However,
bisphenol A (BPA) and phosgene used in the production of commercial
polycarbonates pose major concerns to public health safety. Here, we report a
green pathway to prepare BPA-free polycarbonates (BFPs) by thermal ring-opening
polymerization and photopolymerization. Polycarbonates prepared from two cyclic
carbonates in different mole ratios demonstrated tunable mechanical stiffness,
excellent thermal stability, and high optical transparency. Three-dimensional
(3D) printing of the new BFPs was demonstrated using a two-photon laser direct
writing system and a rapid 3D optical projection printer to produce structures
possessing complex high-resolution geometries. Seeded C3H10T1/2 cells also showed
over 95% viability with potential applications in biological studies. By
combining biocompatible BFPs with 3D printing, novel safe and high-performance
biomedical devices and healthcare products could be developed with broad long
term benefits to society.
PMID- 29345456
TI - Preoccupation of Empty Carriers Decreases Endo-/Lysosome Escape and Reduces the
Protein Delivery Efficiency of Mesoporous Silica Nanoparticles.
AB - Endo-/lysosome escape is a major challenge in nanoparticle-based protein delivery
for cancer therapy. To enhance the endo-/lysosomal escape and increase the
efficacy of protein delivery, current strategies mainly focus on destroying endo
/lysosomes by employing modified nanoparticles, such as pH-sensitive polyplexes,
cell-penetrating peptides, and photosensitive molecules. Herein, we hypothesize
that pretreatment with empty nanocarriers might make endo-/lysosomes occupied and
affect the endo/lysosomal escape of protein subsequently delivery by
nanocarriers. We first treated breast carcinoma MDA-MB-231 cells with a high
concentration of empty nanocarriers, mesoporous silica nanoparticles (MSN), to
occupy the endo-/lysosome. After 2 h, we treated the cells with a lower
concentration of fluorescein isothiocyanate-labeled MSN (MSN-FITC) and
investigated the intracellular spatial and temporal distribution of MSN-FITC and
their colocalization with endo-/lysosomes. We discovered the preoccupation of
endo-/lysosomes by the empty nanocarriers did exist, mainly through changing the
spatial distribution of the subsequently introduced nanocarriers. Furthermore,
for the protein delivery, we observed reduced MSN-saporin delivery after endo
/lysosome preoccupation by MSN empty carriers. A similar result is observed for
the delivery of cytochrome C by MSN but not for the small-molecule anticancer
drug doxorubicin. The results show that the empty nanocarriers inhibit the endo
/lysosome intracellular trafficking process and decrease the endo-/lysosome
escape of proteins subsequently delivered by the nanocarriers. This new
discovered phenomenon of declined endo-/lysosome escape after endo-/lysosome
preoccupation indicates that repeated treatment by nanomaterials with low protein
loading capacity may not yield a good cancer therapeutic effect. Therefore, it
provides a new insightful perspective on the role of nanomaterial carriers in
intracellular protein delivery.
PMID- 29345457
TI - Lithium Expulsion from the Solid-State Electrolyte Li6.4La3Zr1.4Ta0.6O12 by
Controlled Electron Injection in a SEM.
AB - The garnet ionic conductor is one of the promising candidate electrolytes for all
solid-state secondary lithium batteries, thanks to its high lithium ion
conductivity and good thermal and chemical stability. However, its microstructure
is difficult to approach because it is very sensitive to the inquisitive electron
beam. In this study based on a scanning electron microscope (SEM), we found that
the electron beam expulses the lithium out of Li6.4La3Zr1.4Ta0.6O12 (LLZTO), and
the expulsed zone expands to where a stationary beam could extend and penetrate.
The expulsion of metallic lithium was confirmed by its oxidation reaction after
nitrogen inflow into the SEM. This phenomenon may provide us an effective probe
to peer into the conductive nature of this electrolyte. A frame-scan scheme is
employed to measure the expulsion rate by controllable and more uniform incidence
of electrons. Lithium accumulation processes are continuously recorded and
classified into four modes by fitting its growth behaviors into a dynamic
equation that is mainly related to the initial ion concentration and ion
migration rate in the electrolyte. These results open a novel possibility of
using the SEM probe to gain dynamic information on ion migration and lithium
metal growth in solid materials.
PMID- 29345458
TI - Synthesis of Magnetite-Semiconductor-Metal Trimer Nanoparticles through
Functional Modular Assembly: A Magnetically Separable Photocatalyst with
Photothermic Enhancement for Water Reduction.
AB - Hybrid nanoparticles have intrinsic advantages to achieve better activity in
photocatalysis compared to single-component materials, as it can synergistically
combine functional components, which promote light absorption, charge
transportation, surface reaction, and catalyst regeneration. Through functional
modular assembly, a rational and stepwise approach has been developed to
construct Fe3O4-CdS-Au trimer nanoparticles and its derivatives as magnetically
separable catalysts for photothermo-catalytic hydrogen evolution from water. In a
typical step-by-step synthetic process, Fe3O4-Ag dimers, Fe3O4-Ag2S dimers, Fe3O4
CdS dimers, and Fe3O4-CdS-Au trimers were synthesized by seeding growth,
sulfuration, ion exchange, and in situ reduction consequently. Following the same
reaction route, a series of derivative trimer nanoparticles with alternative
semiconductor and metal were obtained for water-reduction reaction. The
experimental results show that the semiconductor acts as an active component for
photocatalysis, the metal nanoparticle acts as a cocatalyst for enhancement of
charge separation, and the Fe3O4 component helps in the convenient separation of
catalysts in magnetic field and improves photocatalytic activity under near
infrared illumination due to photothermic effect.
PMID- 29345459
TI - Bifunctional Hybrid Catalysts with Perovskite LaCo0.8Fe0.2O3 Nanowires and
Reduced Graphene Oxide Sheets for an Efficient Li-O2 Battery Cathode.
AB - In this paper, bifunctional catalysts consisting of perovskite LaCo0.8Fe0.2O3
nanowires (LCFO NWs) with reduced graphene oxide (rGO) sheets were prepared for
use in lithium-oxygen (Li-O2) battery cathodes. The prepared LCFO@rGO composite
was explored as a cathode catalyst for Li-O2 batteries, resulting in an
outstanding discharge capacity (ca. 7088.2 mAh g-1) at the first cycle. Moreover,
a high stability of the O2-cathode with the LCFO@rGO catalyst was achieved over
56 cycles under the capacity limit of 500 mAh g-1 with a rate of 200 mA g-1, as
compared to the Ketjenblack carbon and LCFO NWs. The enhanced electrochemical
performance suggests that these hybrid composites of perovskite LCFO NWs with rGO
nanosheets could be a perspective bifunctional catalyst for the cathode oxygen
reduction and oxygen evolution reactions in the development of next-generation Li
O2 battery cathodes.
PMID- 29345460
TI - Low-Cost Room-Temperature Synthesis of NaV3O8.1.69H2O Nanobelts for Mg Batteries.
AB - Potentially safe and economically feasible magnesium batteries (MBs) have
attracted tremendous research attention as an alternative to high-cost and unsafe
lithium ion batteries. In the current work, for the first time, we report a novel
room-temperature approach to dope the atomic species sodium between the vanadium
oxide crystal lattice to obtain NaV3O8.1.69H2O (NVO) nanobelts. The synthesized
NVO nanobelts are used as electrode materials for MBs. The MB cells demonstrate
stable discharge specific capacity of 110 mA h g-1 at a current density of 10 mA
g-1 and a high cyclic stability, that is 80% capacity retention after 100 cycles,
at a current density of 50 mA g-1. Moreover, the effects of cutoff voltages
(ranging from 2 to 2.6 V) on their electrochemical performance were investigated.
The reason for the limited specific capacity of MBs is attributed to the trapping
of Mg ions inside the NVO lattices. This work opens up a new pathway to explore
different electrode materials for MBs with improved electrochemical performance.
PMID- 29345461
TI - Combined Iron/Hydroxytriazole Dual Catalytic System for Site Selective Oxidation
Adjacent to Azaheterocycles.
AB - This report details a new method for site-selective methylene oxidation adjacent
to azaheterocycles. A dual catalysis approach, utilizing both an iron Lewis acid
and an organic hydroxylamine catalyst, proved highly effective. We demonstrate
that this method provides complementary selectivity to other known catalytic
approaches and represents an improvement over current heterocycle-selective
reactions that rely on stoichiometric activation.
PMID- 29345462
TI - Fluorescent Zn-PDC/Tb3+ Coordination Polymer Nanostructure: A Candidate for
Highly Selective Detections of Cefixime Antibiotic and Acetone in Aqueous System.
AB - Tb3+-doped zinc-based coordination polymer nanospindle bundles (Zn-PDC/Tb3+, or
[Zn(2,5-PDC)(H2O)2].H2O/Tb3+) were synthesized by a simple solution precipitation
route at room temperature, employing Zn(NO3)2, Tb(NO3)3, and 2,5-Na2PDC as the
initial reactants, and a mixture of water and ethanol with the volume ratio of
10:10 as the solvent. The as-obtained nanostructures presented strong fluorescent
emission under the excitation of 298 nm light, which was attributed to the
characteristic emission of the Tb3+ ion. It was found that the above-mentioned
strong fluorescence of the nanostructures could be selectively quenched by
cefixime (CFX) in aqueous solution. The other common antibiotics hardly
interfered. Thus, as-obtained Zn-PDC/Tb3+ nanostructures could be prepared as a
highly sensitive fluorescence probe for selective detection of CFX in an aqueous
system. The corresponding detection limit reached 72 ppb. The theoretic
calculation and UV-vis absorption experiments confirmed that the fluorescence
quenching of Zn-PDC/Tb3+ nanostructures toward CFX should be attributed to the
electron transfer and the fluorescence inner filter effect between the
fluorescent matter and the analyte. In addition, the strong fluorescence of the
nanostructures could also be selectively quenched by acetone in the water system.
PMID- 29345463
TI - (+/-)-Sativamides A and B, Two Pairs of Racemic Nor-Lignanamide Enantiomers from
the Fruits of Cannabis sativa.
AB - (+/-)-Sativamides A (1) and B (2), two pairs of nor-lignanamide enantiomers
featuring a unique benzo-angular triquinane skeleton, were isolated from the
fruits of Cannabis sativa (hemp seed). Their structures were elucidated by
detailed spectroscopic analysis and ECD calculations. The resolution of (+)- and
(-)-sativamides A and B were achieved by chiral HPLC. Pretreatment of
neuroblastoma cells with 1 and 2 significantly reduced the endoplasmic reticulum
(ER) stress-induced cytotoxicity.
PMID- 29345464
TI - Whole Egg Consumption Exerts a Nephroprotective Effect in an Acute Rodent Model
of Type 1 Diabetes.
AB - Nephropathy is a well-characterized complication of type 1 diabetes (T1D),
resulting in proteinuria and urinary loss of micronutrients. We previously found
that a whole egg-based diet maintained vitamin D balance in type 2 diabetic rats
despite excessive urinary losses due to nephropathy. The goal of this study was
to investigate the impact of whole egg consumption in T1D rats. Sprague-Dawley
rats were randomly assigned to T1D or nondiabetic control groups and fed a casein
or whole egg-based diet for 32 days. On day 26, two-thirds of the rats received a
streptozotocin injection to induce T1D. Whole egg consumption attenuated
polyuria, proteinuria, and renal hypertrophy in T1D rats. These data suggest that
dietary intervention with whole egg may offer renal protection in T1D.
PMID- 29345465
TI - Microplastic Abundance and Composition in Western Lake Superior As Determined via
Microscopy, Pyr-GC/MS, and FTIR.
AB - While plastic pollution in marine and freshwater systems is an active area of
research, there is not yet an in-depth understanding of the distributions,
chemical compositions, and fates of plastics in aquatic environments. In this
study, the magnitude, distribution, and common polymers of microplastic pollution
in surface waters in western Lake Superior are determined. Analytical
methodology, including estimates of ambient contamination during sample
collection and processing, are described and employed. Microscopy, pyrolysis-gas
chromatography/mass spectrometry (Pyr-GC/MS), and Fourier transform infrared
spectroscopy (FTIR) were used to quantify and identify microplastic particles. In
surface waters, fibers were the most frequently observed morphology, and, based
upon PyGC/MS analysis, polyvinyl chloride was the most frequently observed
polymer, followed by polypropylene and polyethylene. The most common polymer
identified by FTIR was polyethylene. Despite the low human population in Lake
Superior's watershed, microplastic particles (particularly fibers, fragments, and
films) were identified in western-lake surface waters at levels comparable to
average values reported in studies within Lake Michigan, the North Atlantic
Ocean, and the South Pacific Ocean. This study provides insight into the
magnitude of microplastic pollution in western Lake Superior, and describes in
detail methodology to improve future microplastics studies in aquatic systems.
PMID- 29345466
TI - Flow Photochemistry as a Tool for the Total Synthesis of (+)-Epigalcatin.
AB - The first total synthesis of (+)-epigalcatin was completed in a highly
stereoselective manner starting from piperonal, 3,4-dimethylbenzaldehyde, and
diethyl succinate. l-Prolinol was used as a chiral auxiliary. The crucial step in
this procedure involves the construction of the cyclolignan framework by
continuous-flow photocyclization of a chiral atropisomeric 1,2
bisbenzylidenesuccinate amide ester.
PMID- 29345468
TI - Photochemistry of Solid Films of the Neonicotinoid Nitenpyram.
AB - The environmental fates of nitenpyram (NPM), a widely used neonicotinoid
insecticide, are not well-known. A thin solid film of NPM deposited on a
germanium attenuated total reflectance (ATR) crystal was exposed to radiation
from a low-pressure mercury lamp at 254 nm, or from broadband low pressure
mercury photolysis lamps centered at 350 or 313 nm. The loss during photolysis
was followed in time using FTIR. The photolysis quantum yields (phi), defined as
the number of NPM molecules lost per photon absorbed, were determined to be (9.4
+/- 1.5) * 10-4 at 350 nm, (1.0 +/- 0.3) * 10-3 at 313 nm, and (1.2 +/- 0.4) * 10
2 at 254 nm (+/-2sigma). Imines, one with a carbonyl group, were detected as
surface-bound products and gaseous N2O was generated in low (11%) yield. The UV
vis absorption spectra of NPM in water was different from that in acetonitrile,
dichloromethane, and methanol, or in a thin solid film. The photolytic lifetime
of solid NPM at a solar zenith angle at 35 degrees is calculated to be 36 min,
while that for NPM in water is 269 min, assuming that the quantum yield is the
same as in the solid. Thus, there may be a significant sensitivity to the medium
for photolytic degradation and the lifetime of NPM in the environment.
PMID- 29345467
TI - Cyclic Acyl Disulfides and Acyl Selenylsulfides as the Precursors for Persulfides
(RSSH), Selenylsulfides (RSeSH), and Hydrogen Sulfide (H2S).
AB - The reactions of three model compounds (1-3) for cyclic acyl disulfides and
cyclic acyl selenylsulfides are studied. These compounds were found to be
effective precursors for persulfides (RSSH) and selenylsulfides (RSeSH) upon
reacting with nucleophilic species. They could also act as H2S donors when
interacting with cellular thiols. The most interesting discovery was the
generation of RSeSH from compound 3 under mild conditions. Selenylsulfides
(RSeSH) are expected to be important regulating molecules involved in Sec-related
redox signaling. The method of producing RSeSH should allow researchers to better
understand the chemical biology of RSeSH.
PMID- 29345469
TI - A Large Family of Centrosymmetric and Chiral f-Element-Bearing Iodate Selenates
Exhibiting Coordination Number and Dimensional Reductions.
AB - The exploration of phase formation in the f-element-bearing iodate selenate
system has resulted in 14 novel rare-earth-containing iodate selenates,
Ln(IO3)(SeO4) (Ln = La, Ce, Pr, Nd; LnISeO-1), Ln(IO3)(SeO4)(H2O) (Ln = Sm, Eu;
LnISeO-2), and Ln(IO3)(SeO4)(H2O)2.H2O (Ln = Gd, Dy, Ho, Er, Tm, Yb, Lu, Y;
LnISeO-3), as well as two new thorium iodate selenates, Th(OH)(IO3)(SeO4)(H2O)
(ThISeO-1) and Th(IO3)2(SeO4) (ThISeO-2). LnISeO-3 and ThISeO-2 crystallize in
the chiral space group P212121, while LnISeO-1, LnISeO-2, and ThISeO-1
crystallize in the centrosymmetric space group P21/c. The numbers of both
coordinating and hydrating water molecules crystallized in LnISeO-1, LnISeO-2,
and LnISeO-3 increase along these three series, in line with the increasingly
negative values of hydration enthalpies of heavier trivalent lanthanide ions.
Such a systematic change in compositions, especially the first coordination
sphere of Ln, further induces structural rearrangements, including coordination
number and dimensional reductions. More specifically, the structures of LnISeO-1,
LnISeO-2, and LnISeO-3 have undergone transitions from 2D Ln-oxo layers with 10
coordinate Ln centers to 1D Ln-oxo chains with 9-coordinate Ln centers and then
to 0D Ln-oxo monomers with 8-coordinate Ln centers, respectively. The formation
and characterization of this large family of Ln/Th iodate selenates suggest that
such a mixed-anion system not only exhibits richer structural chemistry but also
can be capable of generating intriguing properties, such as the second-harmonic
generation (SHG) effect.
PMID- 29345470
TI - A Bioinspired Cascade Sequence Enables Facile Assembly of
Methanodibenzo[b,f][1,5]dioxocin Flavonoid Scaffold.
AB - A remarkable bioinspired EDDA-mediated method for the selective construction of
biologically interesting and highly strained bridged
methanodibenzo[b,f][1,5]dioxocin flavonoid scaffold was uncovered by starting
from a variety of readily available acylphloroglucinol and 2
hydroxycinnamaldehyde substrates. This method merges a fascinating olefin
isomerization/hemiacetallization/dehydration/[3 + 3]-type cycloaddition cascade
reaction driven by an in situ generated chromenylium intermediate and provides a
convenient and viable synthetic strategy for the efficient access of such
flavonoid analogues.
PMID- 29345471
TI - Synthesis and Properties of Dithiafulvenyl Functionalized Spiro[fluorene-9,9'
xanthene] Molecules.
AB - Two spiroannulated molecular structures with dithiafulvenyl units functionalized
at the 2,2',7,7'- (SFX-DTF1) and 2,3',6,'7- (SFX-DTF2) positions of a
spiro[fluorene-9,9'-xanthene] core were synthesized. Studies revealed the hole
mobility was significantly influenced by the dithiafulvenyl functionalized
positions in the molecular structure. To explore their primary applications as
hole-transporting materials in perovskite solar cells, SFX-DTF1-based devices
exhibited a power conversion efficiency of 10.67% without the use of p-type
dopants, yielding good air stability.
PMID- 29345472
TI - Current-Driven Motion of Domain Boundaries between Skyrmion Lattice and Helical
Magnetic Structure.
AB - To utilize magnetic skyrmions, nanoscale vortex-like magnetic structures,
experimental elucidation of their dynamics against current application in various
circumstances such as in confined structure and mixture of different magnetic
phases is indispensable. Here, we investigate the current-induced dynamics of the
coexistence state of magnetic skyrmions and helical magnetic structure in a thin
plate of B20-type helimagnet FeGe in terms of in situ real-space observation
using Lorentz transmission electron microscopy. Current pulses with various
heights and widths were applied, and the change of the magnetic domain
distribution was analyzed using a machine-learning technique. The observed
average driving direction of the two-magnetic-state domain boundary is opposite
to the applied electric current, indicating ferromagnetic s-d exchange coupling
in the spin-transfer torque mechanism. The evaluated driving distance tends to
increase with increasing the pulse duration time, current density (>1 * 109
A/m2), and sample temperature, providing valuable information about hitherto
unknown current-induced dynamics of the skyrmion-lattice ensemble.
PMID- 29345473
TI - Highly Sensitive and Ultrastable Skin Sensors for Biopressure and Bioforce
Measurements Based on Hierarchical Microstructures.
AB - Piezoresistive microsensors are considered to be essential components of the
future wearable electronic devices. However, the expensive cost, complex
fabrication technology, poor stability, and low yield have limited their
developments for practical applications. Here, we present a cost-effective,
relatively simple, and high-yield fabrication approach to construct highly
sensitive and ultrastable piezoresistive sensors using a bioinspired
hierarchically structured graphite/polydimethylsiloxane composite as the active
layer. In this fabrication, a commercially available sandpaper is employed as the
mold to develop the hierarchical structure. Our devices exhibit fascinating
performance including an ultrahigh sensitivity (64.3 kPa-1), fast response time
(<8 ms), low limit of detection of 0.9 Pa, long-term durability (>100 000
cycles), and high ambient stability (>1 year). The applications of these devices
in sensing radial artery pulses, acoustic vibrations, and human body motion are
demonstrated, exhibiting their enormous potential use in real-time healthcare
monitoring and robotic tactile sensing.
PMID- 29345474
TI - Total Synthesis of Antiproliferative Parvifloron F.
AB - The first total synthesis of parvifloron F, a bioactive highly oxidized abietane
diterpene, was achieved. The abietane skeleton was constructed by Lewis acid
promoted cyclization. Preliminary structure-activity relationship correlations
were established for the synthetic intermediates against human tumor cell lines.
Certain compounds showed unique selective antiproliferative activity against
triple-negative breast cancer. The oxidation level of the abietane ring affected
the selectivity.
PMID- 29345475
TI - Transition-Metal-Free Regiospecific Aroylation of Nitroarenes Using Ethyl
Arylacetates at Room Temperature.
AB - A novel regiospecific C(sp3)-C(sp2) coupling between ethyl arylacetates and
nitroarenes has been developed to deliver biaryl ketones in excellent yields. The
protocol is metal-free, mild, and compatible with a number of functional groups
on both of the reacting partners.
PMID- 29345476
TI - Adapting a parenting intervention for parents aging out of the child welfare
system: A systematic approach to expand the reach of an evidence-based
intervention.
AB - Parents aging out of the child welfare system face a constellation of unique risk
factors that threaten the well-being of themselves and their children. Although
parenting interventions are an important resource for providing much-needed
services to parents aging out, there is currently a lack of evidence-based
parenting interventions that address the unique needs of this population. The
purpose of this project was to systematically adapt an evidence-based parenting
intervention for parents aging out. An established adaptation framework was used
to guide this process, and acceptability and feasibility outcomes were evaluated
as part of a pilot study of the adapted intervention. Preliminary intervention
adaptations included modifications to program delivery and program content. Study
findings indicated a high level of parent satisfaction with the adapted
intervention but challenges to feasibility because of inconsistent attendance and
the substantial effort required for intervention delivery. This study constitutes
a critical first step toward increasing the reach of evidence-based parenting
interventions among parents aging out of the child welfare system and underscores
the need for continued efforts to develop sustainable and effective parenting
services for this at-risk population. (PsycINFO Database Record
PMID- 29345477
TI - An exploratory study of stress and coping among Black college men.
AB - Research on coping mechanisms among Black Americans is robust, yet there is a
dearth of studies that use qualitative approaches to examine coping specifically
among young Black men. The current and historical landscape of race relations in
the United States calls for additional concern and exploration of this topic. To
fill gaps in this area, this study uncovered the ways Black college men cope with
various stressors that impact their mental health. Eleven qualitative interviews
were conducted with 18- to 25-year-old Black men enrolled at a college in the
Midwest who participated in the Young Black Men, Masculinities, and Mental Health
(YBMen) project. Data were analyzed using a rigorous and accelerated data
reduction technique that involved transferring transcript data onto spreadsheets,
reducing the data, and conducting a rigorous content analysis to generate themes
and subthemes. Participants reported that Black college men cope with stress by
discussing their issues with members of their social support networks, engaging
in physical activities, and relying on themselves. Some respondents reported that
they intentionally avoided dealing with their mental health, whereas others
attempted to make sense of their problems. Substance use, violence, and anger
were all identified as markers of unaddressed stressors. Stigma emerged as a
barrier to seeking help. Study findings highlight within-group differences among
Black college men. Mental health researchers must continue to develop creative
ways to examine stress and coping so that resources can become more culturally
relevant and readily available both within and outside of the spaces Black men
occupy. (PsycINFO Database Record
PMID- 29345478
TI - Racial/ethnic differences of justice-involved youth in substance-related problems
and services received.
AB - This study examined differences in substance-related problems and receipt of
substance-specific counseling in 7 different racial/ethnic groups of justice
involved youth. Data came from a nationally representative sample of 7,073 youth
in residential placement across 36 states representing 5 program types.
Descriptive analyses and regression modeling techniques were used to examine the
relationship between race/ethnicity, substance problems, and substance services.
Results show that more than 2/3 report a history of at least 1 substance-related
problem. Yet, over 12% of youth in residential placement are in programs that do
not offer any substance-related services. This has the greatest implications for
African American and Hispanic youth, who are most likely to be the programs
without these services. Moreover, there are substantive differences in the
prevalence of substance problems by race and ethnicity. American Indian/Alaska
Natives and multiracial youth were significantly more likely to have substance
problems, to be under the influence of drugs and/or alcohol at the time of the
current offense, to have a history of substance problems and above average mental
health need, and to have a history of substance problems and a lifetime suicide
attempt compared to African Americans. Asian youth were similar to African
Americans and had lower rates of substance problems. Asian youth were also the
least likely to be under the influence of drugs and/or alcohol at the time of the
current offense. This study provides important preliminary findings about Asian,
Native Hawaiian/Pacific Islander, and multiracial justice-involved youth and adds
to the knowledge about American Indian/Alaska Native populations. (PsycINFO
Database Record
PMID- 29345479
TI - Culturally adapted transdiagnostic CBT for SSRI-resistant Turkish adolescents: A
pilot study.
AB - The most common mental health problems among adolescents are anxiety and mood
disorders. While disorder-specific cognitive behavior therapy (CBT) is effective
for each of these conditions, the comorbidity between anxiety and mood disorders
indicates a need for the development of evidence-based transdiagnostic
treatments. To examine the efficacy of culturally adapted transdiagnostic CBT (CA
CBT) in reducing symptoms of anxiety and depression in treatment-resistant
Turkish adolescents, 13 adolescent participants with anxiety or mood disorders
who were treatment resistant received 10 sessions of CA-CBT in group format. The
main outcome measures were the Screen for Childhood Child Anxiety Related
Disorders (SCARED), Beck Depression Inventory (BDI), and the Turkish Symptom and
Syndrome Addendum (TSSA), which were assessed at baseline, posttreatment, and at
2-month follow-up. At posttreatment, there were large effect sizes for all
measures: depression scores (BDI, d = .9), anxiety scores (SCARED, d = 1.1), and
the Turkish Symptom and Syndrome Addendum (TSSA, d = 1.6). Moreover, at 2-month
follow-up, depression and anxiety symptoms were either maintained or continued to
improve such that from pretreatment to follow-up the effect sizes were as
follows: depression scores (BDI, d = 1.4), anxiety scores (SCARED, d = 1.7), and
the Turkish Symptom and Syndrome Addendum (TSSA, d = 2.4). In addition, there
were no dropouts across treatment. This open trial suggests that CA-CBT is
effective in reducing anxiety and depression symptoms and that the treatment is
well accepted. A full randomized controlled trial to verify the effectiveness of
transdiagnostic CA-CBT in similar populations is needed. (PsycINFO Database
Record (c) 2018 APA, all rights reserved).
PMID- 29345480
TI - Psychometric evaluation of depression measures with Northern Plains Indians.
AB - Numerous psychometric measurements are used to assess for mental health problems
in Native American and Alaskan Native (AI/AN) populations; however, few studies
have been carried out to assess their validity and reliability within these
populations. This study was designed to assess the validity and reliability of
numerous measures among the Northern Plains Indians. This article is a partial
report, focused on the psychometric measures directed at detecting depression,
namely the Beck Depression Inventory (BDI) II, the Center for Epidemiologic
Studies Depression (CES-D) Scale, the Tri-Ethnic Depression Scale (TEDS), the
Beck Hopelessness Scale (BHS), the Beck Anxiety Inventory (BAI), and the Symptom
Checklist-90-Revised (SCL-90-R). Results revealed moderate to strong correlation
across all measures, alpha coefficients that exceeded published alphas for the
general population, and overall indicated their validity and reliability of these
measures, and a 2-factor solution for the BDI-II. While there were limitations to
the study, analysis of the results supports the use of each measure with the
Northern Plains Indians (NPI) subpopulation, that the NPI subpopulation scored
similar to the general population. (PsycINFO Database Record (c) 2018 APA, all
rights reserved).
PMID- 29345481
TI - The influence of low-barrier and voluntary service policies on survivor
empowerment in a domestic violence housing organization.
AB - The purpose of community-based domestic violence crisis housing programs (e.g.,
shelters) is to provide a safe setting that promotes empowerment for survivors of
intimate partner violence. For staff to reach this aim, the program must have
formal structures and processes in place to support such efforts. This study
explored how low-barrier and voluntary service policies influenced staff
practices and survivor empowerment. Low-barrier policies require that programs
remove barriers that prevent survivors, particularly those who have mental health
concerns and/or addictions, from being able to access services. A voluntary
service policy states that survivors have the right to choose which services, if
any, they would like to engage in during their stay at the program. Survivors'
ability to stay at the housing program is not contingent on their participation
in program services. This exploratory-sequential (QUAL-> quan) mixed-method study
examined how low-barrier and voluntary service policies influenced staff behavior
and how these behaviors then related to survivor empowerment. Qualitative results
revealed that low-barrier and voluntary service were guided by cultural values of
justice and access, encouraged survivor-centered practices among staff, and were
believed to promote survivor autonomy. Quantitative results suggested that when
survivors perceived they had a choice to engage in program services or meet with
an advocate, their empowerment increased. This study has implications for
domestic violence organizational practice and provides evidence about the
contextual factors that support individual empowerment. (PsycINFO Database Record
(c) 2018 APA, all rights reserved).
PMID- 29345482
TI - Subjects adjust criterion on errors in perceptual decision tasks.
AB - The optimal strategy in detection theory is to partition the decision axis at a
criterion C, labeling all events that score above C "Signal", and all those that
fall below "Noise." The optimal position of C, C*, depends on signal probability
and payoffs. If observers place their criterion at some place other than C*, they
suffer a loss in the Expected Value (EV) of payoffs over the course of many
decisions. We provide an explicit equation for the degree of loss, where it is
shown that the falloff in value will be steep in contexts of good discrimination
and will be a flatter gradient in contexts of poor discrimination. It is these
gradients of loss in EV that, in theory, drive C toward C*, strongly when
discrimination is good, weakly when discrimination is poor. When signal
probabilities or distributions variances are unequal, the basins of attraction
are asymmetric, so that dynamic adjustments in C will be asymmetric, and thus, as
we show, will leave it biased. We address our analysis to acquisition speed,
response variability, discrimination reversal and other aspects of discriminated
performance. In the final section, we develop an error correction model that
predicts empirically observed deviations from C* that are inconsistent with the
standard model, but follow from the proposed model given knowledge of d'.
(PsycINFO Database Record
PMID- 29345483
TI - Editorial: Journal article reporting standards.
AB - In this editorial, the author notes that this issue of American Psychologist
features a pair of important articles related to newly updated standards for
reporting research in psychology in scientific journals, covering both
quantitative (Appelbaum et al., 2018) and qualitative (Levitt et al., 2018)
research. The increasing breadth and complexity of research, and the importance
of communicating it effectively, requires user-friendly resources that can be
applied widely to scientific studies. These two articles are intended to serve
that purpose, and to encourage thoroughness and accuracy in research reporting,
for psychologists and other scientists in broader academic communities. The
articles, known as the Journal Article Reporting Standards (JARS) reports, are
based on the work of a task force appointed by the American Psychological
Association (APA) Publications and Communications Board in 2015. (PsycINFO
Database Record
PMID- 29345484
TI - Journal article reporting standards for quantitative research in psychology: The
APA Publications and Communications Board task force report.
AB - Following a review of extant reporting standards for scientific publication, and
reviewing 10 years of experience since publication of the first set of reporting
standards by the American Psychological Association (APA; APA Publications and
Communications Board Working Group on Journal Article Reporting Standards, 2008),
the APA Working Group on Quantitative Research Reporting Standards recommended
some modifications to the original standards. Examples of modifications include
division of hypotheses, analyses, and conclusions into 3 groupings (primary,
secondary, and exploratory) and some changes to the section on meta-analysis.
Several new modules are included that report standards for observational studies,
clinical trials, longitudinal studies, replication studies, and N-of-1 studies.
In addition, standards for analytic methods with unique characteristics and
output (structural equation modeling and Bayesian analysis) are included. These
proposals were accepted by the Publications and Communications Board of APA and
supersede the standards included in the 6th edition of the Publication Manual of
the American Psychological Association (APA, 2010). (PsycINFO Database Record
PMID- 29345485
TI - Journal article reporting standards for qualitative primary, qualitative meta
analytic, and mixed methods research in psychology: The APA Publications and
Communications Board task force report.
AB - The American Psychological Association Publications and Communications Board
Working Group on Journal Article Reporting Standards for Qualitative Research
(JARS-Qual Working Group) was charged with examining the state of journal article
reporting standards as they applied to qualitative research and with generating
recommendations for standards that would be appropriate for a wide range of
methods within the discipline of psychology. These standards describe what should
be included in a research report to enable and facilitate the review process.
This publication marks a historical moment-the first inclusion of qualitative
research in APA Style, which is the basis of both the Publication Manual of the
American Psychological Association (APA, 2010) and APA Style CENTRAL, an online
program to support APA Style. In addition to the general JARS-Qual guidelines,
the Working Group has developed standards for both qualitative meta-analysis and
mixed methods research. The reporting standards were developed for psychological
qualitative research but may hold utility for a broad range of social sciences.
They honor a range of qualitative traditions, methods, and reporting styles. The
Working Group was composed of a group of researchers with backgrounds in varying
methods, research topics, and approaches to inquiry. In this article, they
present these standards and their rationale, and they detail the ways that the
standards differ from the quantitative research reporting standards. They
describe how the standards can be used by authors in the process of writing
qualitative research for submission as well as by reviewers and editors in the
process of reviewing research. (PsycINFO Database Record
PMID- 29345486
TI - Facilitating pipeline progress from doctoral degree to first job.
AB - The sequence of professional development within psychology from doctoral
education to first job represents a period of remarkable professional and
personal growth for each trainee. However, this sequence also contains a variety
of barriers that hinder progress through the pipeline. The myriad individual-,
program-, and system-level barriers encountered by trainees in health
service/other applied service psychology and in research basic/applied psychology
are identified. To actively and systematically facilitate improved passage
through major transition points, individual trainee and trainer, program- and
system-level action steps are recommended. In addition, emphasis is placed on
ensuring that the psychology education and training culture prioritizes the
progress, creativity, and flourishing of trainees and supports their movement
through branching pipelines in their training and in their careers. (PsycINFO
Database Record
PMID- 29345487
TI - On the general acceptance of confessions research: Opinions of the scientific
community.
AB - Eighty-seven experts on the psychology of confessions-many of whom were highly
published, many with courtroom experience-were surveyed online about their
opinions on 30 propositions of relevance to deception detection, police
interrogations, confessions, and relevant general principles of psychology. As
indicated by an agreement rate of at least 80%, there was a strong consensus that
several findings are sufficiently reliable to present in court. This list
includes but is not limited to the proposition that the risk of false confessions
is increased not only by explicit threats and promises but by 2 common
interrogation tactics-namely, the false evidence ploy and minimization tactics
that imply leniency by offering sympathy and moral justification. Experts also
strongly agreed that the risk of undue influence is higher among adolescents,
individuals with compliant or suggestible personalities, and those with
intellectual impairments or diagnosed psychological disorders. Additional
findings indicated that experts set a high standard before judging a proposition
to be sufficiently reliable for court-and an even higher standard on the question
"Would you testify?" Regarding their role as scientific experts, virtually all
respondents stated that their primary objective was to educate the jury and that
juries are more competent at evaluating confession evidence with assistance from
an expert than without. These results should assist trial courts and expert
witnesses in determining what aspects of the science are generally accepted and
suitable for presentation in court. (PsycINFO Database Record
PMID- 29345488
TI - Risky business: Correlation and causation in longitudinal studies of skill
development.
AB - Developmental theories often posit that changes in children's early psychological
characteristics will affect much later psychological, social, and economic
outcomes. However, tests of these theories frequently yield results that are
consistent with plausible alternative theories that posit a much smaller causal
role for earlier levels of these psychological characteristics. Our article
explores this issue with empirical tests of skill-building theories, which
predict that early boosts to simpler skills (e.g., numeracy or literacy) or
behaviors (e.g., antisocial behavior or executive functions) support the long
term development of more sophisticated skills or behaviors. Substantial
longitudinal associations between academic or socioemotional skills measured
early and then later in childhood or adolescence are often taken as support of
these skill-building processes. Using the example of skill-building in
mathematics, we argue that longitudinal correlations, even if adjusted for an
extensive set of baseline covariates, constitute an insufficiently risky test of
skill-building theories. We first show that experimental manipulation of early
math skills generates much smaller effects on later math achievement than the
nonexperimental literature has suggested. We then conduct falsification tests
that show puzzlingly high cross-domain associations between early math and later
literacy achievement. Finally, we show that a skill-building model positing a
combination of unmeasured stable factors and skill-building processes can
reproduce the pattern of experimental impacts on children's mathematics
achievement. Implications for developmental theories, methods, and practice are
discussed. (PsycINFO Database Record
PMID- 29345496
TI - Feedback from the European Bioanalysis Forum: focus workshop on current analysis
of immunogenicity: best practices and regulatory hurdles.
AB - European Bioanalysis Forum Workshop, Lisbon, Portugal, September 2016: At the
recent European Bioanalysis Forum Focus Workshop, 'current analysis of
immunogenicity: best practices and regulatory hurdles', several important
challenges facing the bioanalytical community in relation to immunogenicity
assays were discussed through a mixture of presentations and panel sessions. The
main areas of focus were the evolving regulatory landscape, challenges of assay
interferences from either drug or target, cut-point setting and whether
alternative assays can be used to replace neutralizing antibody assays. This
workshop report captures discussions and potential solutions and/or
recommendations made by the speakers and delegates.
PMID- 29345497
TI - Experiences of menopause, self-management strategies for menopausal symptoms and
perceptions of health care among immigrant women: a systematic review.
AB - OBJECTIVE: To systematically review the published literature relating to
experiences of menopause, self-management strategies for menopausal symptoms and
health-care needs among immigrant women. METHODS: A systematic literature search
of English-language publications was performed using Medline, Embase, PsychInfo,
Cinahl and Scopus. Twenty-four papers reporting on 19 studies met our inclusion
criteria and investigated immigrant women's experiences of menopause and/or their
self-management strategies for menopausal symptoms and/or their perceptions of
menopause-specific health care. FINDINGS: Of the 19 studies, 15 reported symptoms
experienced during the menopausal transition. Three studies included questions
regarding self-management strategies for menopausal symptoms and four enquired
about perceptions of menopause-specific health care. Although the heterogeneity
of the studies makes comparison difficult, their findings are broadly consistent.
Immigrant women reported more vasomotor symptoms and other physical symptoms and
poorer mental health than non-immigrant women. The few studies that investigated
self-management strategies for menopausal symptoms found that these were
influenced by culture and those that assessed perceptions of menopause-specific
health care found that they were mostly dissatisfied with the care they had
received. CONCLUSION: More research is needed to improve understanding of how
immigrant women manage the menopausal transition and how to provide culturally
relevant menopause-specific health care.
PMID- 29345498
TI - Effects of blueberry and cranberry consumption on type 2 diabetes glycemic
control: A systematic review.
AB - The metabolic effects of cranberry and blueberry consumption on glycemic control
have been evaluated in vitro and in animal models as well as in human studies,
although findings have not been systematically reviewed yet. Therefore, a
systematic review was carried out of relevant randomized clinical trials (RCTs)
in order to assess the effect of berries (blueberry and cranberry) consumption on
type 2 diabetes (T2DM) glycemic control. Some evidences were also discussed on
the anti-diabetic mechanisms exerted by berries polyphenols. Studies were
identified by searching electronic databases: LILACS, PubMed/MEDLINE, Scopus, The
Cochrane Library and Web of Science. Three authors independently searched and
extracted RCTs in which the effect of berries (cranberry or blueberry)
consumption on T2DM glycemic control was assessed. A total of 7 RCTs, involving
270 adults with type 2 diabetes were included. Despite the heterogeneity of the
administration forms (in natura, dried, extract, preparations - juice), dosage,
duration of the intervention and type of population of the studies involving
these two berries some studies highlight the potential benefit of berries,
especially of blueberry, on glucose metabolism in T2DM subjects. Daily cranberry
juice (240 mL) consumption for 12 weeks and blueberry extract or powder
supplementation (9.1 to 9.8 mg of anthocyanins, respectively) for 8 to 12 weeks
showed a beneficial effect on glucose control in T2DM subjects. Those results
indicate a promising use of these berries in T2DM management; although more
studies are required to better understand the mechanisms involved.
PMID- 29345499
TI - Disrupted behaviour in grammatical morphology in French speakers with autism
spectrum disorders.
AB - Mixed and inconsistent findings have been reported across languages concerning
grammatical morphology in speakers with Autism Spectrum Disorders (ASD). Some
researchers argue for a selective sparing of grammar whereas others claim to have
identified grammatical deficits. The present study aimed to investigate this
issue in 26 participants with ASD speaking European French who were matched on
age, gender and SES to 26 participants with typical development (TD). The groups
were compared regarding their productivity and accuracy of syntactic and
agreement categories using the French MOR part-of-speech tagger available from
the CHILDES. The groups significantly differed in productivity with respect to
nouns, adjectives, determiners, prepositions and gender markers. Error analysis
revealed that ASD speakers exhibited a disrupted behaviour in grammatical
morphology. They made gender, tense and preposition errors and they omitted
determiners and pronouns in nominal and verbal contexts. ASD speakers may have a
reduced sensitivity to perceiving and processing the distributional structure of
syntactic categories when producing grammatical morphemes and agreement
categories. The theoretical and cross-linguistic implications of these findings
are discussed.
PMID- 29345500
TI - Effects of L-Arginine Supplementation on Leukogram, Inflammatory Bowel
Infiltrates and Immunoglobulins with 5-FU Use in Rats.
AB - This study evaluated the effects of L-arginine supplementation on blood
parameters, kidney and liver function, immunoglobulins and noninflammatory
infiltrates in the small intestines of rats subjected to chemotherapy with 5
fluorouracil (5-FU). Thirty-two Wistar rats were randomly distributed into 4
groups (8 rats/group): an untreated control group, and test groups receiving one
dose of 5-FU (G5-FU group), one dose of 5-FU and 295 mg L-arginine/day (GArg295
group) or one dose of 5-FU and 458 mg L-arginine/day (GArg458 group). Neutrophil
count, platelet count, serum IgA, and fibrinogen levels in GArg295 and GArg458
remained within normal limits after chemotherapy. In addition, in GArg458 the
inflammatory bowel infiltrates improved in 57% of the rats, which showed mild
inflammation. The results suggest that daily supplementation with 295 or 458 mg L
arginine attenuates the side effects of 5-FU, including thrombocytopenia and
neutropenia, and modulates IgA production. Supplementation with 458 mg of L
arginine/day can also reduce mucositis levels in the small intestine after 5-FU
chemotherapy.
PMID- 29345501
TI - 'It's nothing you could ever prepare anyone for': the experiences of young people
and their families following parental stroke.
AB - AIMS: This study sought to explore the experiences of young people (aged 8-16)
and their families following parental acquired brain injury (ABI), with the aim
of developing an understanding of the ways in which members of a family make
sense of events post-injury, and to consider the implications of different
perspectives on adjustment and coping. DESIGN: The study applied a qualitative
approach using a thematic analysis methodology. PROCEDURE: Individual semi
structured interviews were conducted with 10 individuals from three families
affected by parental stroke. RESULTS: Findings suggested that post-injury,
families experienced a period of uncertainty in which they were required to
renegotiate their roles and adjust to the loss associated with parental stroke.
Additionally, the psychosocial wellbeing of young people was negatively affected,
whilst protective and coping strategies were recognised. CONCLUSIONS: The
research offers an insight into the processes that may contribute to patterns of
interpersonal relating that could negatively impact on adjustment. Provision of
adequate information, psychological and practical support during recovery may
therefore be crucial elements of supporting young people and their families in
adjusting to the challenges posed by stroke.
PMID- 29345502
TI - Extended 3D and 4D cumulative plots for evaluation of unmatched incurred sample
reanalysis.
AB - AIM: Incurred sample reanalysis (ISR) helps ensure the reliability of
pharmacokinetic studies. An appropriate graph may facilitate the evaluation of an
unmatched reanalyses or a failed ISR test. METHODS: We evaluated different ways
of visualizing multidimensional ISR data using an extended cumulative ISR plot.
RESULTS: 3D and 4D cumulative ISR plots enable comprehensive data analysis using
a single plot. We propose to use color for percentage difference classes in bar
and XY-scatter plots. For the latter the shape of symbols may represent analyte
concentration class, study phase, analyst or subject. CONCLUSION: The extended 3D
and 4D cumulative ISR plots facilitate in-study monitoring and post-study
inspection of data. It helps find the root cause of unmatched ISR, thus
increasing reliability of bioanalytical data.
PMID- 29345503
TI - Effectiveness of the Biophysical Barriers to the Peridural Fibrosis in Rat
Laminectomy Model.
AB - PURPOSE: Peridural fibrosis which could occur after the spinal surgery could
adhere neural tissue closely and may cause to neural entrapment symptoms and
require surgical reintervention. AIM OF THE STUDY: Present study was designed to
reduce occurrence of peridural fibrosis in rat laminectomy model by using
biophysical barriers called hyaluronic acid (HAS) dural barrier, activated
polyethylene glycol and polyethylene imine (PEG) dural barrier, and platelet-rich
plasma (PRP). MATERIALS AND METHODS: In this study, 2 of 26 male Wistar albino
rats (325-350 g body weight), which were not included into study groups were
sacrificed by removing their total blood and their blood was used for preparation
of PRP, and remaining rats were randomly delivered into four groups called SHAM,
HAS, PEG, and PRP groups. Then L3-4-5 laminectomy was performed to all animals
and experimental agents were administered to the selected groups mentioned above.
Spinal colons of all animals were removed gross total after 6-week period and
investigated histopathologically. Additionally, real-time-polymerase chain
reaction was used to obtain collagen type I and type III, transforming growth
factor-1beta, and tumor necrosis factor-alpha gene expressions. RESULTS: All
results demonstrated that polyethylene glycol and polyethylene imine dural
barrier and PRP could decrease peridural fibrosis formation efficiently in rat.
CONCLUSION: Present study results suggested that to reduce or block formation of
peridural fibrosis, either polyethylene glycol and polyethylene imine dural
barrier or PRP could be used effectively in human subjects after they will be
closely investigated in future studies.
PMID- 29345504
TI - Development of the HOOSglobal to Assess Patient-Reported Outcomes in Patients
Undergoing Hip Preservation Procedures.
AB - BACKGROUND: The creation of a single patient-reported outcome (PRO) platform
validated across hip preservation, osteoarthritis (OA), and total hip
arthroplasty (THA) populations may reduce barriers and streamline the routine
collection of PROs in clinical practice. As such, the purpose of this study was
to determine if augmenting the Hip disability and Osteoarthritis Outcome Score
Joint Replacement (HOOS, JR) with additional HOOS questions would result in a PRO
platform that could be used across a wider spectrum of hip patient populations.
HYPOTHESIS: The HOOS, JR would demonstrate a notable ceiling effect, but by
augmenting the HOOS, JR with additional HOOS questions, a responsive PRO platform
could be created. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2.
METHODS: Using preoperative and postoperative HOOS responses from a sample of 304
patients undergoing periacetabular osteotomy (PAO), additional items were
identified to augment the HOOS, JR. The psychometric properties of a newly
created PRO tool (HOOSglobal) were then compared with the HOOS, JR and other PRO
instruments developed for patients with hip OA and/or undergoing THA. RESULTS: By
augmenting the HOOS, JR with 2 additional questions, the HOOSglobal was more
responsive than all other included PRO tools and had significantly fewer maximum
postoperative scores than the HOOS, JR ( P < .0001), HOOS-Physical Function Short
form ( P < .0001), Western Ontario and McMaster Universities Osteoarthritis Index
( P = .02), University of California, Los Angeles activity scale ( P = .0002),
and modified Harris Hip Score ( P = .04). The postoperative HOOSglobal score
threshold associated with patients achieving the patient acceptable symptom state
(PASS) was 62.5. CONCLUSION: The HOOSglobal is a valid and responsive PRO tool
after PAO and may potentially provide the orthopaedic community with a PRO
platform to be used across hip-related subspecialties. For patients undergoing
PAO, a postoperative HOOSglobal score >=62.5 was associated with patients
achieving the PASS.
PMID- 29345505
TI - The pharmacological management of metabolic syndrome.
AB - INTRODUCTION: The metabolic syndrome includes a constellation of several well
established risk factors, which need to be aggressively treated in order to
prevent overt type 2 diabetes and cardiovascular disease. While recent guidelines
for the treatment of individual components of the metabolic syndrome focus on
cardiovascular benefits as resulted from clinical trials, specific recent
recommendations on the pharmacological management of metabolic syndrome are
lacking. The objective of present paper was to review the therapeutic options for
metabolic syndrome and its components, the available evidence related to their
cardiovascular benefits, and to evaluate the extent to which they should
influence the guidelines for clinical practice. Areas covered: A Medline
literature search was performed to identify clinical trials and meta-analyses
related to the therapy of dyslipidemia, arterial hypertension, glucose metabolism
and obesity published in the past decade. Expert commentary: Our recommendation
for first-line pharmacological are statins for dyslipidemia, renin-angiotensin
aldosteron system inhibitors for arterial hypertension, metformin or
sodium/glucose cotransporter 2 inhibitors or glucagon-like peptide 1 receptor
agonists (GLP-1RAs) for glucose intolerance, and the GLP-1RA liraglutide for
achieving body weight and waist circumference reduction.
PMID- 29345506
TI - Effects of physical and depressive symptoms on the sexual life of Turkish women
in the climacteric period.
AB - OBJECTIVE: To assess the effects of physical and depressive symptoms on the
sexual life of women in the climacteric period. METHODS: This study was conducted
with 572 women at a university hospital. The Beck Depression Inventory (BDI),
Menopause Rating Scale (MRS) and Female Sexual Function Index (FSFI) were used to
evaluate depressive symptoms, intensity of menopausal symptoms and sexual
function. RESULTS: Sexual dysfunction and depressive symptoms were determined in
86.4% and 54.9% of the women, respectively. In univariate analysis, women without
health insurance, with low income, being married for longer than 21 years and
being in menopause had low FSFI but high BDI and MRS scores. In multiple
regression analysis, advanced age of women, women with low income, unemployed
women, low educated women and their husbands and women with depressive symptoms
had low FSFI scores. There was a negative relationship between total FSFI and MRS
and BDI scores. CONCLUSION: Determination and treatment of sexual, emotional and
physical problems in the climacteric period are very important for the
improvement of the quality of life of women.
PMID- 29345508
TI - Response by Twin Italian Hub Hospitals in a Double Seismic Event: A Retrospective
Observational Investigation.
AB - INTRODUCTION: The objectives of this study were to compare prevalence rates of
different pathologies, ambulance system and emergency department management
times, and patient survival and hazard ratios for codes 2 and 3 in two hub
hospitals in Modena in the 36-month period across the stages of two major
earthquakes in short sequence in Northern Italy in 2012. METHODS: Clinical
records pertaining to the emergency care of patients were analyzed and only those
assigned status codes 2 and 3 by ambulance professionals were included (if the
assessment was confirmed by emergency department triage). The statistical
analysis of data was divided by three time periods studied: before,
during/between, and after the earthquakes. RESULTS: Among the 2,278 retained
records, there were no statistically significant differences in the prevalence of
the main pathologies presented at the two hubs in the studied period. A Cox
regression model was used to analyze the survival of patients in the different
stages of the emergency; there were no statistically significant differences in
the hazard ratios of death before, during, and after the earthquake. The study
found a significant increase in emergency department treatment times. DISCUSSION:
Redundancies in the Modena medical system were found to have compensated for
damaged hospital facilities. In particular, they helped emergency systems
reorganize themselves faster in order to bring medical assistance to people
during and around seismic events with as a minimal amount of disruption as
possible. CONCLUSION: The Modena medical system was redundant and ensured that
disrupted emergency systems were reorganized and put back online while damaged
hospital facilities were compensated for/reproduced elsewhere.
PMID- 29345509
TI - Corrigendum.
PMID- 29345507
TI - Ovarian tissue cryopreservation in young females through the Oncofertility
Consortium's National Physicians Cooperative.
AB - AIM: To characterize the clinical indications of females (<15 years old)
undergoing ovarian tissue cryopreservation (OTC) through the Oncofertility
Consortium's National Physicians Cooperative (OC-NPC). PATIENTS & METHODS: The
clinical indications of 114 females who underwent OTC were classified, and their
incidence was compared with childhood cancer databases. RESULTS:
Leukemias/myeloproliferative diseases/myelodysplastic diseases and
hemoglobinopathies were the most prevalent oncologic and nononcologic indications
for OTC, respectively. The frequencies of malignant bone tumors and soft tissue
and other extraosseous sarcomas were higher in the OC-NPC cohort relative to the
general population, while CNS/intracranial/intraspinal neoplasms, retinoblastoma
and hepatic tumors were lower. CONCLUSION: Those opting for OTC through the OC
NPC are at highest fertility risk, indicating that the appropriate patient
populations are being identified. [Formula: see text].
PMID- 29345510
TI - Preliminary Evaluation of the Viability of Peritoneal Drainage Catheters
Implanted in Rats for Extended Durations.
AB - : Purpose/Aim: In developing a novel peritoneal oxygenation therapy, catheters
implanted into the peritoneal cavity became obstructed with omental tissue and
prevented the infusion and removal of fluid from the peritoneal cavity. The
obstruction of peritoneal catheters is a significant failure in researching
various peritoneal treatments as further fluid administration is no longer
possible. The purpose of this preliminary study was to determine the most
effective catheter design for infusion and removal of fluid into the peritoneal
cavity of rats. MATERIALS AND METHODS: Four types of catheters were tested
including the Jackson-Pratt, round fluted drain, flat fluted drain, and an
original design. Three of each catheter type were surgically placed into the
peritoneal cavity of rats (n = 12). In order to test the efficacy of each
catheter, saline was infused and extracted twice daily. Catheters were scored on
a weighted scale based on the amount of time they remained patent, the subjective
force needed for extraction/infusion, and the amount of saline removed. RESULTS:
The round and flat fluted drain catheters remained patent for the full duration
of the study (12 days) compared to the other models which failed after 7 days.
These catheters also yielded a high average for extracted saline volume and an
easy extraction/infusion. CONCLUSIONS: The round and flat fluted drain catheters
were recognized as viable options to be used in rats for peritoneal drain studies
of up to 12 days.
PMID- 29345511
TI - Clinical Characteristics of Herpes Simplex Virus Associated Anterior Uveitis.
AB - PURPOSE: The aim of this study is to describe the clinical characteristics of
molecularly proven Herpes simplex virus (HSV) anterior uveitis. METHODS: The
literature on HSV anterior uveitis whereby the diagnosis was confirmed by
polymerase chain reaction (PCR) and or Goldmann-Witmer coefficient in aqueous
humor was reviewed. Three studies from Europe and one from Japan could be
included. RESULTS: It was observed that HSV anterior uveitis is mostly an acute
unilateral disease mainly occurring in middle-aged people with a predominance in
females. The incidence of keratitis in HSV is between 33 and 41%. High
intraocular pressure is frequently observed and ranged from 46 to 90%. Sectorial
iris atrophy may be absent, especially early in the disease. CONCLUSION: The
clinical characteristics of HSV anterior uveitis can mimic other viral and non
infectious anterior uveitis entities especially at onset. Aqueous humor analysis
for PCR and GWC can be useful in case of suspected viral uveitis.
PMID- 29345512
TI - Physical Activity, Function, and Mortality in Advanced Age: A Longitudinal Follow
Up (LiLACS NZ).
AB - The relationship between physical activity, function, and mortality is not
established in advanced age. Physical activity, function, and mortality were
followed in a cohort of Maori and non-Maori adults living in advanced age for a
period of 6 years. Generalized linear regression models were used to analyze the
association between physical activity and Nottingham Extended Activities of Daily
Living scale, whereas Kaplan-Meier survival analysis and Cox proportional hazard
models were used to assess the association between the physical activity and
mortality. The hazard ratio for mortality for those in the least active physical
activity quartile was 4.1 for Maori and 1.8 for non-Maori compared with the most
active physical activity quartile. There was an inverse relationship between
physical activity and mortality, with lower hazard ratios for mortality at all
levels of physical activity. Higher levels of physical activity were associated
with lower mortality and higher functional status in advanced-aged adults.
PMID- 29345513
TI - No Benefit in Neurologic Outcomes of Survivors of Out-of-Hospital Cardiac Arrest
with Mechanical Compression Device.
AB - INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) is a major cause of death and
morbidity in the United States. Quality cardiopulmonary resuscitation (CPR) has
proven to be a key factor in improving survival. The aim of our study was to
investigate the outcomes of OHCA when mechanical CPR (LUCAS 2 Chest Compression
SystemTM) was utilized compared to conventional CPR. Although controlled trials
have not demonstrated a survival benefit to the routine use of mechanical CPR
devices, there continues to be an interest for their use in OHCA. METHODS: We
conducted a retrospective observational study of OHCA comparing the outcomes of
mechanical and manual chest compressions in a fire department based EMS system
serving a population of 1.4 million residents. Mechanical CPR devices were
geographically distributed on 11 of 33 paramedic ambulances. Data were collected
over a 36-month period and outcomes were dichotomized based on utilization of
mechanical CPR. The primary outcome measure was survival to hospital discharge
with a cerebral performance category (CPC) score of 1 or 2. RESULTS: This series
had 3,469 OHCA reports, of which 2,999 had outcome data and met the inclusion
criteria. Of these 2,236 received only manual CPR and 763 utilized a mechanical
CPR device during the resuscitation. Return of spontaneous circulation (ROSC) was
attained in 44% (334/763) of the mechanical CPR resuscitations and in 46%
(1,020/2,236) of the standard manual CPR resuscitations (p = 0.32). Survival to
hospital discharge was observed in 7% (52/763) of the mechanical CPR
resuscitations and 9% (191/2,236) of the manual CPR group (p = 0.13). Discharge
with a CPC score of 1 or 2 was observed in 4% (29/763) of the mechanical CPR
resuscitation group and 6% (129/2,236) of the manual CPR group (p = 0.036).
CONCLUSIONS: In our study, use of the mechanical CPR device was associated with a
poor neurologic outcome at hospital discharge. However, this difference was no
longer evident after logistic regression adjusting for confounding variables.
Resuscitation management following institution of mechanical CPR, specifically
medication and airway management, may account for the poor outcome reported.
Further investigation of resuscitation management when a mechanical CPR device is
utilized is necessary to optimize survival benefit.
PMID- 29345514
TI - Design and Validation of an Instrumented Uneven Terrain Treadmill.
AB - Studying human and animal locomotion on an uneven terrain can be beneficial to
basic science and applied studies for clinical and robotic applications.
Traditional biomechanical analysis of human locomotion has often been limited to
laboratory environments with flat, smooth runways and treadmills. The authors
modified a regular exercise treadmill by attaching wooden blocks to the treadmill
belt to yield an uneven locomotion surface. To ensure that these treadmill
modifications facilitated biomechanical measurements, the authors compared ground
reaction force data collected while a subject ran on the modified instrumented
treadmill with a smooth surface with data collected using a conventional
instrumented treadmill. Comparisons showed only minor differences. These results
suggest that adding an uneven surface to a modified treadmill is a viable option
for studying human or animal locomotion on an uneven terrain. Other types of
surfaces (eg, compliant blocks) could be affixed in a similar manner for studies
on other types of locomotion surfaces.
PMID- 29345515
TI - Safety of biologic agents for psoriasis in patients with viral hepatitis.
AB - INTRODUCTION: Biologics are highly effective, important treatment options for
moderate-to-severe psoriasis. Biologics are well tolerated and have few side
effects. However, the use of biologics in patients with concomitant chronic viral
hepatitis is debatable. Recent reports have suggested a very low associated risk
of reactivation of chronic hepatitis B (HBV) and C (HCB). OBJECTIVE: To evaluate
the safety and effectiveness of biologics for moderate to severe psoriasis
patients with concomitant chronic viral hepatitis. METHODS: We followed 39
patients with psoriasis and concurrent chronic viral hepatitis (chronic inactive
and occult cases) with no clinical signs and/or lab indication of active liver
disease) treated with biologic agents for at least 24 weeks. Patients were
regularly monitored for reactivation of viral hepatitis with liver enzymes, viral
DNA load, and viral markers. RESULTS: There was no evidence of viral reactivation
until the last available lab investigation results (done three months after
stopping the medication). None of the patients showed signs or symptoms of liver
failure. CONCLUSION: The use of biologic therapy appeared safe and effective in
this small cohort of selected patients with chronic HBV and HCV infection. Close
monitoring for HBV and HCV viral load is recommended for patients with high-risk
factors.
PMID- 29345516
TI - Association between Weather-Related Factors and Cardiac Arrest of Presumed
Cardiac Etiology: A Prospective Observational Study Based on Out-of-Hospital Care
Data.
AB - OBJECTIVE: The objective of this study was to determine the association between
weather-related factors and out-of-hospital cardiac arrest (OHCA) of presumed
cardiac etiology. METHODS: This was a prospective observational study performed
in a prehospital setting. Data from the Emergency Medical Service in Hamburg
(Germany) and data from the local weather station were evaluated over a 5-year
period. Weather data (temperature, humidity, air pressure, wind speed) were
obtained every minute and matched with the associated rescue mission data. Lowess
Regression analysis was performed to assess the relationship between the above
mentioned weather-related factors and OHCA of presumed cardiac etiology.
Additionally, varying measuring-ranges were defined for each weather-related
factor in order to compare them with each other with regard to the probability of
occurrence of OHCA. RESULTS: During the observation period 1,558 OHCA with
presumed cardiac etiology were registered (age: 67 +/- 19 yrs; 62% male; hospital
admission: 37%; survival to hospital discharge: 6.7%). Compared to moderate
temperatures (5 - 25 degrees C), probability of OHCA-occurrence increased
significantly at temperatures above 25 degrees C (p = 0.028) and below 5 degrees
C p = 0.011). Regarding air humidity, probability of OHCA-occurrence increased
below a threshold-value of 75% compared to values above this cut-off (p = 0.006).
Decreased probability was seen at moderate atmospheric pressure (1000 hPa - 1020
hPa), whereas increased probability was seen above 1020 hPa (p = 0.023) and below
1000 hPa (p = 0.035). Probability of OHCA-occurrence increased continuously with
increasing wind speed (p < 0.001). CONCLUSIONS: There are associations between
several weather-related factors such as temperature, humidity, air pressure, and
wind speed, and occurrence of OHCA of presumed cardiac etiology. Particularly
dangerous seem to be cold weather, dry air and strong wind.
PMID- 29345517
TI - PET-adapted therapy for advanced Hodgkin lymphoma - systematic review.
AB - INTRODUCTION: Positron emission tomography-computed tomography (PET-CT) performed
after two chemotherapy cycles (PET-2) has become an accepted prognostic tool in
Hodgkin lymphoma (HL). We evaluated the effect of PET-adapted strategy on outcome
in advanced stage HL. METHODS: In August 2017, we searched electronic databases,
conference proceedings and ongoing trials. We included all studies in which
treatment modification for advanced HL was performed based on the results of the
interim PET scan. The primary analysis included randomized controlled trials
(RCTs). Outcomes were progression-free survival (PFS) and overall survival (OS).
RESULTS: We identified 13 studies (4 RCTs, 7 phase II and 2 retrospective
studies), conducted between 1999 and 2014, including 6856 patients. Of the four
RCTS: one used therapy escalation, one did de-escalation and two trials performed
both. Outcomes were assessed at different time point between 2 and 5 years. Three
RCTs for de-escalating therapy, obtained similar outcomes despite reducing
therapy, with a 2-year PFS of 88-92% (6 escalated BEACOPP (EB) vs. 4 ABVD
cycles), a 5-year PFS of 91-92% (6/8 EB vs. 4 EB cycles) and a 5-year PFS of 80
82% (6 ABVD vs. omitting bleomycin after two successful ABVD cycles). Two RCTs
implemented escalation. The randomization was between adding rituximab or not. In
both trials, it did not affect outcome, with a 4-year PFS of 68-69% (addition of
rituximab to BEACOPP after 2 ABVD cycles) and 5-year PFS of 88-90% (addition of
rituximab to EB after 2 EB cycles). Performing true randomization between PET
adapted and a standard ABVD control arm was not feasible, given historical data.
CONCLUSIONS: This systematic review of PET-adapted therapy, mainly based on RCTs,
suggests that a change to the treatment paradigm is appropriate in advanced HL.
PMID- 29345518
TI - Bacterial pathogenesis and interleukin-17: interconnecting mechanisms of immune
regulation, host genetics, and microbial virulence that influence severity of
infection.
AB - Interleukin-17 (IL-17) is a pro-inflammatory cytokine involved in the control of
many different disorders, including autoimmune, oncogenic, and diverse infectious
diseases. In the context of infectious diseases, IL-17 protects the host against
various classes of microorganisms but, intriguingly, can also exacerbate the
severity of some infections. The regulation of IL-17 expression stems, in part,
from the activity of Interleukin-23 (IL-23), which drives the maturation of
different classes of IL-17-producing cells that can alter the course of
infection. In this review, we analyze IL-17/IL-23 signalling in bacterial
infection, and examine the interconnecting mechanisms that link immune
regulation, host genetics, and microbial virulence in the context of bacterial
pathogenesis. We consider the roles of IL-17 in both acute and chronic bacterial
infections, with a focus on mouse models of human bacterial disease that involve
infection of mucosal surfaces in the lungs, urogenital, and gastrointestinal
tracts. Polymorphisms in IL-17-encoding genes in humans, which have been
associated with heightened host susceptibility to some bacterial pathogens, are
discussed. Finally, we examine the implications of IL-17 biology in infectious
diseases for the development of novel therapeutic strategies targeted at
preventing bacterial infection.
PMID- 29345519
TI - "I Just Roll Over, Pick Myself Up, and Carry On!" Exploring the Fall-Risk
Experience of Canadian Masters Athletes.
AB - OBJECTIVES: The risk of falling increases in adults aged 65 years and older. A
common barrier to take up physical activity in sedentary older adults is the fear
of falls and injury. Experiences of master athletes can provide insights into
management of the risk of falling. The purpose of this phenomenological study was
to explore the fall-risk experience of masters athletes actively competing in
sport. METHODS: Masters athletes aged 55 years and older (N = 22) described their
experiences in semistructured interviews. Data were analyzed through an
interpretive-constructivist paradigm using inductive content analysis. RESULTS:
Five dominant themes emerged: acceptance, learning, awareness, resilience, and
self-fulfillment. Participants of this study reported an acceptance of the risk
they take in sport for falls and injuries in their pursuits for self-fulfillment.
DISCUSSION: Findings indicate that master athletes accept the risk for falls and
injuries in sport, find ways to adapt, and continue to compete because it is self
fulfilling. Sharing their experiences might inspire other older adults to get
active as a rewarding means of remaining independent.
PMID- 29345520
TI - Correlates of Physical Activity Among Middle-Aged and Older Adults With Hazardous
Drinking Habits in Six Low- and Middle-Income Countries.
AB - We investigated physical activity (PA) correlates among middle-aged and older
adults (aged >=50 years) with hazardous drinking patterns in six low- and middle
income countries. Cross-sectional data were analyzed from the World Health
Organization's Study on Global Ageing and Adult Health. Hazardous drinking was
defined as consuming >7 (females) or >14 (males) standard drinks per week.
Participants were dichotomized into low (i.e., not meeting 150 min of moderate
PA/week) and moderate-high physically active groups. Associations between PA and
a range of correlates were examined using multivariable logistic regressions. The
prevalence of low PA in 1,835 hazardous drinkers (60.5 +/- 13.1 years; 87.9%
males) was 16.2% (95% confidence interval [13.9%, 18.9%]). Older age, living in
an urban setting, being unemployed, depression, underweight, obesity, asthma,
visual impairment, poor self-rated health, and higher levels of disability were
identified as significant PA correlates. The current data provide important
guidance for future interventions to assist older hazardous drinkers to engage in
regular PA.
PMID- 29345521
TI - Development and validation of an ELISA to study panitumumab pharmacokinetics.
AB - AIM: Panitumumab is a monoclonal antibody directed against EGFR that is approved
for the treatment of metastatic colorectal cancer. To investigate its
pharmacokinetics and concentration-response relationship, a validated assay is
required. RESULTS: An ELISA assay was developed and validated according to
international recommendations. Six calibrators (ranging from 0.1 to 20 mg/l) plus
one anchor point (50 mg/l) and three quality controls (0.45, 2 and 8 mg/l) were
defined. The limit of detection, lower limit of quantification and upper limit of
quantification were 0.033, 0.112 and 10 mg/l, respectively. CONCLUSION: This
method is validated and can be used to study pharmacokinetics of panitumumab or
to perform therapeutic drug monitoring.
PMID- 29345522
TI - Goal setting practice in chronic low back pain. What is current practice and is
it affected by beliefs and attitudes?
AB - INTRODUCTION: Goal setting, led by the patient, is promising as an effective
treatment for the management of chronic low back pain (CLBP); however, little is
known about current practice. The aims of the study were to explore (1) current
goal setting practice in CLBP among physiotherapists; (2) perceived barriers to
goal setting in CLBP; and (3) relationship between clinician's attitudes and
beliefs and goal setting practice. METHOD: A cross-sectional observational
survey. RESULTS: The majority of respondents used goal setting with the main aim
of facilitating self-management. The greatest number of goals were set with 50%
therapist/50% patient involvement. The most common perceived barriers to goal
setting related to time constraints and lack of skill and confidence. A higher
biomedical score for treatment orientation of the therapist was associated with a
lower patient involvement score. CONCLUSION: Goal setting is common practice for
CLBP and is perceived as a high priority. It is more often a collaboration
between therapist and patient rather than patient-led with treatment orientation
of the physiotherapist a predictor of patient involvement. Education of
healthcare professionals needs to include better understanding of chronic pain to
orient them away from a biomedical treatment approach, as well as to enhance
skills in facilitating patient involvement in goal setting.
PMID- 29345524
TI - Recovery and Performance in Sport: Consensus Statement.
AB - The relationship between recovery and fatigue and its impact on performance has
attracted the interest of sport science for many years. An adequate balance
between stress (training and competition load, other life demands) and recovery
is essential for athletes to achieve continuous high-level performance. Research
has focused on the examination of physiological and psychological recovery
strategies to compensate external and internal training and competition loads. A
systematic monitoring of recovery and the subsequent implementation of recovery
routines aims at maximizing performance and preventing negative developments such
as underrecovery, nonfunctional overreaching, the overtraining syndrome,
injuries, or illnesses. Due to the inter- and intraindividual variability of
responses to training, competition, and recovery strategies, a diverse set of
expertise is required to address the multifaceted phenomena of recovery,
performance, and their interactions to transfer knowledge from sport science to
sport practice. For this purpose, a symposium on Recovery and Performance was
organized at the Technical University Munich Science and Study Center
Raitenhaslach (Germany) in September 2016. Various international experts from
many disciplines and research areas gathered to discuss and share their knowledge
of recovery for performance enhancement in a variety of settings. The results of
this meeting are outlined in this consensus statement that provides central
definitions, theoretical frameworks, and practical implications as a synopsis of
the current knowledge of recovery and performance. While our understanding of the
complex relationship between recovery and performance has significantly increased
through research, some important issues for future investigations are also
elaborated.
PMID- 29345525
TI - Adsorption of lead ion from aqueous solution by modified walnut shell: kinetics
and thermodynamics.
AB - The novel modified walnut shell (WNS-MAH) with higher adsorption capacity for
lead ion was prepared by reacting walnut shell (WNS) with maleic anhydride. Both
WNS and WNS-MAH were analyzed by SEM and FTIR. The adsorption capacity of WNS-MAH
for lead ion was evaluated at different adsorbent doses, pHs, time and
temperatures. The adsorption kinetics and adsorption isotherms were investigated
from (298 to 318) K. The adsorption kinetics of lead ion onto WNS-MAH were fitted
using pseudo-first-order, pseudo-second-order and Elovich models. It was found
that pseudo-second-order model gives the best correlation results. The diffusion
mechanism was determined according to the intraparticle diffusion equation and
Boyd equation. Results suggested the adsorption process was governed by film
diffusion. The equilibrium adsorption data were fitted with the Freundlich model
and the Langmuir model. The maximum adsorption capacity of WNS-MAH for lead ion
removal was 221.24 mg/g at 318 K. The equilibrium adsorption data were analyzed
using the D-R model, and the feature concentration ([Formula: see text]) was
determined to distinguish chemisorption and physisorption. The thermodynamic
parameters (DeltaG, DeltaH and DeltaS) were calculated. Additionally, the
regeneration property was studied and the adsorption process was confirmed by
energy disperse spectroscopy.
PMID- 29345523
TI - Hexim1, an RNA-controlled protein hub.
AB - Hexim1 acts as a tumor suppressor and is involved in the regulation of innate
immunity. It was initially described as a non-coding RNA-dependent regulator of
transcription. Here, we detail how 7SK RNA binds to Hexim1 and turns it into an
inhibitor of the positive transcription elongation factor (P-TEFb). In addition
to its action on P-TEFb, it plays a role in a variety of different mechanisms: it
controls the stability of transcription factor components and assists binding of
transcription factors to their targets.
PMID- 29345526
TI - Differential Gait Patterns by History of Falls and Knee Pain Status in Healthy
Older Adults: Results From the Baltimore Longitudinal Study of Aging.
AB - Consideration of knee pain can be crucial for identifying fall-related gait
patterns. While walking, gait parameters at usual speed were examined in persons
with different falls and knee pain status. A total of 439 adults aged 60-92 years
participated in this study. Persons with a history of falls had a wider stride
width (p = .036) and longer double support time (p = .034) than nonfallers. In
the absence of knee pain, fallers had longer double support time than nonfallers
(p = .012), but no differences in double support time by history of falls were
observed in participants with knee pain. With slower gait speed, fallers with
knee pain have narrower stride width and larger hip range of motion (p = .027 and
p = .001, respectively). Results suggest the importance of considering knee pain
in fall studies for better understanding the fall-related differential gait
mechanisms and for designing fall prevention intervention strategies.
PMID- 29345528
TI - Linguistic analysis of patients with mood and anxiety disorders during cognitive
behavioral therapy.
AB - We analyzed the verbal behavior of patients with mood or/and anxiety disorders
during psychotherapy. Investigating the words people used, we expected
differences due to cognitive and emotional foci in patients with depression vs.
anxiety. Transcripts of therapy sessions from 85 outpatients treated with
cognitive behavioral therapy were analyzed using the software program Linguistic
Inquiry and Word Count. Multivariate group comparisons were carried out
investigating the LIWC-categories first-person-singular pronouns, sad, anxiety
and fillers. Differences between the three diagnostic groups were found in verbal
utterances related to sadness (p = .05). No differences were found for first
person-singular pronouns and content-free fillers. Comparing the distinct groups
"depression" and "anxiety", depressed patients used more words related to sadness
(p = .01). Mood and anxiety disorders differ in the experience of emotions, but
only slightly in self-focused attention. This points to differences in language
use for different diagnostic groups and may help to improve diagnostic procedures
or language-driven interventions which enhance therapists' attention to patients'
verbal behavior.
PMID- 29345527
TI - Does Problem Focused Coping Buffer the Effects of Trait Anxiety on Depressive
Symptoms of Chronic Urticaria Patients?
AB - The present study examined the moderating role of problem-focused coping in trait
anxiety-depressive symptoms' relationship in patients with chronic urticaria
(CU). Eighty-eight CU patients, who applied to an outpatient clinic of Clinical
Immunology and Allergic Diseases, filled out a questionnaire set including State
Trait Anxiety Inventory, Ways of Coping Inventory, and Beck Depression Inventory.
The results suggested that CU patients high on trait anxiety reported more
depressive symptoms, and the ones using more problem-focused coping (PFC)
strategies reported less depressive symptoms. Also, PFC strategies moderated
trait anxiety-depressive symptoms relation. Accordingly, PFC strategies did not
lead to any significant difference in CU patients who were low on trait anxiety
in terms of the level of depressive symptoms. However, CU patients with high
trait anxiety experienced significantly less depressive symptoms if they used
more PFC strategies. The findings were discussed in the light of the relevant
literature.
PMID- 29345529
TI - Effects of Telestroke on Thrombolysis Times and Outcomes: A Meta-analysis.
AB - OBJECTIVE: Telestroke systems are tools, used to provide an advanced stroke care
in regions without sufficient neurologic services. We performed this meta
analysis to assess the effects of telemedicine on treatment times and clinical
outcomes of acute stroke care. METHODS: A literature search of PubMed, SCOPUS,
and Cochrane CENTRAL was conducted for original studies investigating
telemedicine applications in acute stroke care. Dichotomous data on treatment
outcomes were pooled as odds ratios (ORs), while continuous data on thrombolysis
times were pooled as mean differences (MDs) with 95% confidence interval (CI),
using RevMan software (version 5.3). RESULTS: Pooling data from 26 studies (6605
thrombolysed patients) showed no significant differences between the telestroke
and control groups in terms of in-hospital mortality (OR = 1.21, 95% CI [0.98,
1.49]), 90-day mortality (OR = 1.08, 95% CI [0.85, 1.37]), symptomatic
intracranial hemorrhage (sICH) (OR = 1.10, 95% CI [0.79, 1.53]), and favorable
clinical outcome at discharge (OR = 1.03, 95% CI [0.69, 1.53]) and 90 days later
(OR = 0.99, 95% CI [0.82, 1.18]). The onset-to-door (OTD) duration (MD = -10.4
minutes, 95% CI [-14.79, -.01]) and length of hospital stay (MD = -0.55 days, 95%
CI [-1.02, -0.07]) were significantly shorter in the telestroke group, compared
to the control group. Although the overall effect estimate (under the fixed
effect model) showed a significant decrease in the onset-to-treatment (OTT)
duration in the telestroke group (MD = -5.83 minutes, 95% CI [-8.57, -3.09]),
employing the random-effects model for between-study heterogeneity abolished this
significance (MD = -5.90 minutes, 95% CI [-13.23, 1.42]). CONCLUSION: Telestroke
significantly reduced OTD and hospital stay durations in stroke patients without
increasing the risk of mortality or sICH. Therefore, telemedicine can improve
stroke care in regional areas with minor experience in thrombolysis. Further
randomized controlled trials are needed to assess the benefits of telestroke
systems, especially in terms of cost-effectiveness and quality of life outcomes.
PMID- 29345530
TI - Who benefits from psychotherapies for adult depression? A meta-analytic update of
the evidence.
AB - It is not clear whether specific target groups for psychotherapies in adult
depression benefit as much from these treatments as other patients. We examined
target groups that have been examined in randomized trials, including women,
older adults, students, minorities, patients with general medical disorders, and
specific types of depression, and we examined where patients were recruited. We
conducted subgroup and multivariate metaregression analyses in a sample of 256
trials (with 332 comparisons) comparing psychotherapy with an inactive control
condition. Only 22% of the studies had low risk of bias (RoB), heterogeneity was
high and there was a considerable risk of publication bias. A meta-regression
analysis among low RoB studies showed that effect sizes found for studies among
women, older adults, patients with general medical disorders, patients recruited
from primary care, and patients scoring above a cut-off on a self-rating
depression scale, did not differ significantly from effect sizes from other
studies. For other target groups, the number of low RoB studies was too small to
draw any conclusion. We found few indications that psychotherapies for adult
depression are more or less effective in women, older adults, patients with
comorbid general medical disorders, and primary care patients.
PMID- 29345531
TI - How Tailoring the Mode of Information Presentation Influences Younger and Older
Adults' Satisfaction with Health Websites.
AB - Although older adults are increasingly using online health information, many
websites are not senior-friendly, which might lead to user-problems and
dissatisfaction among older people. It has been suggested that websites targeted
at older adults should take into account age-related abilities and limitations,
for example by providing the opportunity to adjust the modality (i.e., "mode") of
information presentation based on visual and auditory capabilities. This study
investigates the effects of a mode-tailored website, allowing users to self
tailor the mode of information presentation, on younger and older adults'
satisfaction with health websites. The results from a 5 (condition: tailored vs.
text, text with visuals, text with audiovisual, combination) * 2 (age: younger
[25-45] vs. older [>= 65] adults) experimental study (N = 563) show that mode
tailoring positively influenced satisfaction with the attractiveness and
comprehensibility of the website, as compared to non-tailored conditions. These
effects on website satisfaction were not different for younger and older adults.
The current study provides relevant insights for researchers and practitioners in
the field of digital health communication.
PMID- 29345532
TI - Ischemic Preconditioning: No Influence on Maximal Sprint Acceleration
Performance.
AB - Ischemic preconditioning (IPC) was initially developed to protect the myocardium
from ischemia through altered cardiocyte metabolism. Because of the observed
effects on metabolism and oxygen kinetics, IPC gained interest as a potential
ergogenic aid in sports. Limited research evaluating the effects of IPC on
maximal short-duration activities has been performed, and of the existing
literature, mixed outcomes resulting from intrasubject variation may have clouded
the efficacy of this technique for enhancing sprint performance. Therefore, the
current study employed a randomized repeated-measures crossover design with IPC,
placebo (SHAM), and control conditions while using sprint-trained athletes (N =
18) to determine the effect of IPC (3 * 5-min occlusions, with 5-min
reperfusion), concluding 15 min prior to maximal 10-s and 20-m sprinting. A
visual analog scale was used in conjunction with the sprint trials to evaluate
any possible placebo effect on performance. Despite a "significantly beneficial"
perception of the IPC treatment compared with the SHAM trials (P < .001), no
changes in sprint performance were observed after either the IPC or SHAM
condition over 10 m (IPC Delta < 0.01 [0.02] s, SHAM Delta < 0.01 [0.02] s) or
20 m (IPC Delta = -0.01 [0.03] s, SHAM Delta < 0.01 [0.03] s) compared with
control. Thus, an IPC protocol does not improve 10- or 20-m sprint performance in
sprint-trained athletes.
PMID- 29345533
TI - Daily Bicycling in Older Adults May be Effective to Reduce Fall Risks-A Case
Control Study.
AB - Older adults gain many health benefits from riding bicycles regularly. We aimed
to explore whether older persons who ride bicycles regularly have better balance
than controls. Balance control and voluntary stepping were assessed in 20 older
adults aged 65-85 years who live in an agricultural community village and who
ride bicycles regularly, and 30 age- and gender-matched nonbicycle riders (NBR).
Self-reported function and fear of fall were also assessed. Bicycle riders (BR)
showed significantly better balance, faster voluntary stepping, and better self
reported advanced lower-extremity function compared with NBR. The results might
suggest that bicycling regularly preserves balance control and speed of voluntary
stepping in older adults because bicycling might maintain specific balance
coordination patterns. The results should be treated with caution as bicycle
riders were older adults who selected an active lifestyle (i.e., bicycling as
well as living in an agricultural village) that may bias the results.
PMID- 29345534
TI - A new stipitate species of Crepidotus from India and Thailand, with notes on
other tropical species.
AB - A new Asian species of Crepidotus (Basidiomycota, Agaricales), C. asiaticus, is
presented based on morphological and nuc rDNA internal transcribed spacer (ITS1
5.8S-ITS2 = ITS) and large subunit (28S) sequence data. This new species, found
in India and Thailand, is characterized by the centrally stipitate medium-sized
basidiomata, orange to reddish brown pileus, white to brownish orange lamellae,
and white stipe. Based on morphology, C. asiaticus is similar to the neotropical
C. thermophilus. However, the microscopic characters, especially the size and
shape of the basidiospores, can be used to distinguish these two taxa, as well as
their geographic distributions. Further, the phylogenetic position of C.
asiaticus is unique based on ITS and 28S nuc rDNA sequences. Melanomphalia
argipoda, described by Singer from Ecuador, is also a stipitate Crepidotus based
on an ITS sequence of the type specimen, so the new combination is proposed here.
Phylogenetically, the three species form a monophyletic group with the Asiatic C.
asiaticus forming the sister lineage to the neotropical C. argipodus and C.
thermophilus.
PMID- 29345535
TI - Coping Styles Mediate Perfectionism Associations with Depression Among
Undergraduate Students.
AB - To better understand depression among adolescent university students, this study
was designed to examine coping style as a potential mediator between
perfectionism and depression. Participants comprised 510 undergraduate students
from Malaysia. Structural Equation Modelling demonstrated that personal standards
perfectionism and task-focused coping style were negatively associated with
depression, while emotion-focused coping style, avoidant coping style, and
evaluative concerns perfectionism were positively associated with depression.
Multiple mediator modelling provided evidence that coping styles partially
mediated the relationship between perfectionism and depression. These findings
advance current knowledge by suggesting how perfectionism may contribute to
depression and may inform the development of more effective prevention and
intervention programs for depression.
PMID- 29345536
TI - UASB-septic tank as an alternative for decentralized wastewater treatment in
Mexico.
AB - The aim of this work was to evaluate the performance of a UASB-septic tank as a
decentralized treatment of high-strength municipal wastewater under two different
HRTs (48 and 72 h). Thus, a lab-scale (44.85 L) UASB-septic tank constituted by
three compartments was operated under HRT 72 and 48 h. Removal efficiencies of
total chemical oxygen demand (COD), biological oxygen demand (BOD5) and suspended
solids (SS) ranged from 60% to 80% for the first two parameters and from 70% to
90% for the last one. According to the statistical analysis, it was established
that decreasing HRT from 72 to 48 h did not affect the performance of the UASB
septic tank; therefore, the latter HRT is recommended to be used for operation.
In the first compartment, most of the organic matter removal was carried out,
while the other two compartments served as polishing. Over the course of six
months, the VS concentration and VS/TS ratio in sludge blanket decreased,
indicating digestion and stabilization of the retained solids. Also, an increase
of 4% in sludge volume was observed; thus, time for desludging would be
approximately five years. Comparison of the UASB-septic tank and the UASB reactor
showed that both systems had similar performance regarding effluent
concentrations of organic matter and solids. Thus, under low volumetric organic
load conditions (less than 20 mg COD/L h), the former is an attractive option for
municipal wastewater treatment.
PMID- 29345537
TI - Postmatch Perceived Exertion, Feeling, and Wellness in Professional Soccer
Players.
AB - PURPOSE: To assess postmatch perceived exertion, feeling, and wellness according
to the match outcome (winning, drawing, or losing) in professional soccer
players. METHODS: In total, 12 outfield players were followed during 52 official
matches where the outcomes (win, draw, or lose) were noted. Following each match,
players completed both a 10-point Borg scale modified by Foster and an 11-point
Hardy and Rejeski scale rating of perceived feeling. Rating of perceived sleep
quality, stress, fatigue, and muscle soreness was collected separately on a 7
point scale the day following each match. RESULTS: Player rating of perceived
exertion was higher by a very large magnitude following a loss compared with a
draw or a win and higher by a small magnitude after a draw compared with a win.
Players felt more pleasure after a win compared with a draw or loss and more
displeasure after a loss compared with draw. The players reported a largely and
moderately better perceived sleep quality, less stress, and fatigue following a
win compared with a draw or a loss and a moderately bad perceived sleep quality,
higher stress, and fatigue following a draw compared with a loss. In contrast,
only a trivial-small change was observed in perceived muscle soreness between all
outcomes. CONCLUSION: Match outcomes moderately to largely affect rating of
perceived exertion, feeling, sleep quality, stress, and fatigue, whereas
perceived muscle soreness remains high regardless of the match outcome. However,
winning a match decreases the strain and improves both pleasure and wellness in
professional soccer players.
PMID- 29345538
TI - Real-time monitoring of nanoscale TiO2 concentration by spectrophotometry:
implications of agglomeration due to natural organic matter and multivalent ions.
AB - The study of the environmental fate of nanoscale TiO2 (n-TiO2) is a major recent
research focus which requires a rapid and accurate on-site concentration
determination method. Inductively coupled plasma mass spectroscopy (ICP-MS) has
been the most widely used method for determining the concentration of n-TiO2 in
environmental samples; however, poses many challenges, such as hazardous
hydrofluoric acid pre-treatment and clear limitations in mobile on-site
measurement and monitoring. This study demonstrates that industrial wastewater
containing natural organic matter (NOM) can present a major challenge to the
analysis of n-TiO2 by ICP-MS, and introduces a spectrophotometry technique that
can be used as an alternative. The results suggest that spectrophotometry methods
can be more accurate than slurry nebulization ICP-MS for measuring the
concentrations of n-TiO2 in wastewater containing NOM under low salt conditions.
Furthermore, this study demonstrates the use of a portable flow-through
spectrophotometer for use in applications of wastewater treatment and
environmental monitoring with real-time feedback of n-TiO2 concentrations. The
ability to detect and monitor n-TiO2 will greatly assist in improving the
understanding of hazards and risks that emerging nanomaterials pose to the
environment and the public health.
PMID- 29345539
TI - Working Memory Updating: Load and Binding.
AB - In the present study, we aimed to examine how specific objects are updated in
working memory. We compared conditions in which contents or content-context
bindings from working memory were both encoded and updated (Experiment 1). In
addition, for bindings, we manipulated the memory load (i.e., number of contents)
to maintain during updating. Results indicated that memory load did not
specifically affect the process; rather, the content-context binding (vs. single
contents) was critical in determining the increase in response latencies. Results
were replicated even in Experiment 2, in which we manipulated the spatial
locations of the to-be-recognized probes. Results showed evidence of a potential
dissociation between updating of memory contents-only and content-context
bindings. In addition, memory load and spatial coherence between phases and probe
recognition did not interact with updating performance. Overall, results were
taken as a contribution toward mapping the complex nature of the updating
mechanism.
PMID- 29345541
TI - Running Mechanics and Metabolic Responses With Water Bottles and Bottle Belt
Holders.
AB - PURPOSE: To determine whether differential kinematics, kinetics, rates of energy
use, and cardiopulmonary responses occur during running with water bottles and
bottle belt holders compared with running only. METHODS: Trained runners (N = 42;
age 27.2 [6.4] y) ran on an instrumented treadmill for 4 conditions in a
randomized order: control run (CON), handheld full water bottle (FULL; 16.9 fluid
oz; 454 g), handheld half-full water bottle (HALF; 8.4 fluid oz; 227 g), and
waist-worn bottle belt holder (BELT; hydration belt; 676 g). Gas exchange was
measured using a portable gas analyzer. Kinetic and kinematic responses were
determined by standard 3-dimensional videographic techniques. Interactions of
limb side (right and left) by study condition (CON, FULL, HALF, and BELT) were
tested for rates of oxygen use and energy expenditure and kinematic and kinetic
parameters. RESULTS: No significant limb-side * condition interactions existed
for rates of oxygen use or energy expenditure. A significant interaction occurred
with sagittal elbow flexion (P < .001). Transverse pelvic-rotation excursions
differed on average 3.8 degrees across conditions. The minimum sagittal hip
flexion moment was higher in the right leg in the HALF and BELT conditions
compared with CON (P < .001). CONCLUSIONS: Carrying water by hand or on the waist
does not significantly change the kinematics of running motion, rates of oxygen
use and energy expenditure, or cardiopulmonary measures over short durations.
Runners likely make adjustments to joint moments and powers that preserve balance
and protect the lower-extremity joints while maintaining rates of oxygen use and
energy expenditure.
PMID- 29345542
TI - Effects of Late-Night Training on "Slow-Wave Sleep Episode" and Hour-by-Hour
Derived Nocturnal Cardiac Autonomic Activity in Female Soccer Players.
AB - PURPOSE: To assess the sensitivity of nocturnal heart-rate-variability-monitoring
methods to the effects of late-night soccer training sessions in female athletes.
METHODS: Eleven female soccer players competing in the first division of the
Portuguese soccer league wore heart-rate monitors during sleep at night
throughout a 1-wk competitive in-season microcycle, after late-night training
sessions (n = 3) and rest days (n = 3). Heart rate variability was analyzed
through "slow-wave sleep episode" (10-min duration) and "hour by hour" (all the
RR intervals recorded throughout the hours of sleep). Training load was
quantified by session rating of perceived exertion (281.8 [117.9] to 369.0
[111.7] arbitrary units [a.u.]) and training impulse (77.5 [36.5] to 110.8 [31.6]
a.u.), added to subjective well-being ratings (Hopper index = 11.6 [4.4] to 12.8
[3.2] a.u.). These variables were compared between training and rest days using
repeated-measures analysis of variance. RESULTS: The log-transformed slow-wave
sleep-episode cardiac autonomic activity (lnRMSSD [natural logarithm of the
square root of the mean of the sum of the squares of differences between adjacent
normal RR intervals] varying between 3.92 [0.57] and 4.20 [0.60] ms; [Formula:
see text]; 95% confidence interval, .01-.26), lnHF (natural logarithm of high
frequency), lnLF (natural logarithm of low frequency), lnSD1 (natural logarithm
of short-term beat-to-beat variability), and lnSD2 (natural logarithm of long
term beat-to-beat variability), and the nontransformed LF/HF were not different
among night-training session days and rest days (P > .05). Considering the hour
by-hour method (lnRMSSD varying between 4.05 [0.35] and 4.33 [0.32] ms; [Formula:
see text]; 95% confidence interval, .26-.52), lnHF, lnLF, lnSD1, and lnSD2 and
the nontransformed LF/HF were not different among night-training session days and
rest days (P > .05). CONCLUSION: Late-night soccer training does not seem to
affect nocturnal slow-wave sleep-episode and hour-by-hour heart-rate-variability
indices in highly trained athletes.
PMID- 29345540
TI - Cost-effectiveness analysis of asymptomatic peripheral artery disease screening
with the ABI test.
AB - Screening for asymptomatic peripheral artery disease (aPAD) with the ankle
brachial index (ABI) test is hypothesized to reduce disease progression and
cardiovascular (CV) events by identifying individuals who may benefit from early
initiation of medical therapy. Using a Markov model, we evaluated the cost
effectiveness of initiating medical therapy (e.g. statin and ACE-inhibitor) after
a positive ankle-brachial index (ABI) screen in 65-year-old patients. We modeled
progression to symptomatic PAD (sPAD) and CV events with and without ABI
screening, evaluating differences in costs and quality-adjusted life years
(QALYs). The cost of the ABI test, physician visit, new medication, CV events,
and interventions for sPAD were incorporated in the model. We performed
sensitivity analysis on model variables with uncertainty. Our model found an
incremental cost of US $338 and an incremental QALY of 0.00380 with one-time ABI
screening, resulting in an incremental cost-effectiveness ratio (ICER) of
$88,758/QALY over a 35-year period. The variables with the largest effects in the
ICER were aPAD disease prevalence, cost of monthly medication after a positive
screen and 2-year medication adherence rates. Screening high-risk populations,
such as tobacco users, where the prevalence of PAD may be 2.5 times higher,
decreases the ICER to $24,092/QALY. Our analysis indicates the cost effectiveness
of one-time screening for aPAD depends on prevalence, medication costs, and
adherence to therapies for CV disease risk reduction. Screening in higher-risk
populations under favorable assumptions about medication adherence results in the
most favorable cost effectiveness, but limitations in the primary data preclude
definitive assessment of cost effectiveness.
PMID- 29345543
TI - Physical Activity and Sitting Time Are Specifically Associated With Multiple
Chronic Diseases and Medicine Intake in Brazilian Older Adults.
AB - The purpose of the study was to clarify the independent association between
sedentary behavior and physical activity with multiple chronic diseases and
medicine intake in older individuals. Sedentary behavior and physical activity
were measured by questionnaires. Diseases and medication use were self-reported.
Poisson's regression was adopted for main analysis, through crude and adjusted
prevalence ratio and confidence interval of 95%. For men, sedentary time >4
hr/day presented a 76% higher prevalence of >=2 chronic diseases, while physical
inactivity increases the likelihood of using >=2 medicines in 95%. For women,
sedentary behavior >4 hr/day presented an 82% and 43% greater prevalence for >=2
chronic diseases and the intake of >=2 medicines, respectively. Sedentary
behavior represents an independent associated factor of multiple chronic diseases
in older men and women. In addition, inactivity for men and sedentarism for women
are associated with the amount of medicine intake.
PMID- 29345544
TI - Editorial.
PMID- 29345545
TI - Decisive Moment: A Metric to Determine Success in Elite Karate Bouts.
AB - PURPOSE: To evaluate the concept of decisive moment (DM) as a novel analysis
approach providing insights into factors leading to successful high-performance
kumite karate outcomes using time-motion variables. DM represents the moment from
which 1 of the 2 opponents uninterruptedly dominates the other until the end of
the fight. METHODS: A total of 120 elite seniors (60 men and 60 women) World
Karate Federation combats were analyzed during 2 World Championships (2012 and
2014). Specific characteristics of karate combat (strategy, technique, tactic,
target, and effectiveness) were evaluated and classified in 3 sections: at,
before, and after DM. RESULTS: DM occurred at about 49% (32.8%) of bout duration.
Up to DM no clearly identifiable differences in performance characteristics were
found between winners and losers. At and after DM, an offensive strategy with
focus on upper-limb techniques, attack and counterattack, targeting the head
showed highest potential to achieve and maintain dominance and to win. After DM,
losers showed increasingly reactive techniques, mainly timed attacks and
combinatory techniques. CONCLUSION: The DM concept presents a novel approach to
time-motion analysis, which for the first time allowed identification of clear
discriminating factors of success and defeat in kumite karate at the highest
performance level.
PMID- 29345546
TI - Enhanced biosorption of transition metals by living Chlorella vulgaris
immobilized in Ca-alginate beads.
AB - In this study freely suspended and Ca-alginate immobilized C. vulgaris cells were
used for the biosorption of Fe(II), Mn(II), and Zn(II) ions, from the aqueous
solution. Experimental data showed that biosorption capacity of algal cells was
strongly dependent on the operational condition such as pH, initial metal ions
concentration, dosages, contact time and temperature. The maximum biosorption of
Fe(II) 43.43, Mn(II) 40.98 and Zn(II) 37.43 mg/g was achieved with Ca-alginate
immobilized algal cells at optimum pH of 6.0, algal cells dosage 0.6 g/L, and
contact time of 450 min at room temperature. The biosorption efficiency of freely
suspended and immobilized C. vulgaris cells for heavy metals removal from the
industrial wastewater was validated. Modeling of biosorption kinetics showed good
agreements with pseudo-second-order. Langmuir and D-R isotherm models exhibited
the best fit of experimental data. The thermodynamic parameters (DeltaG degrees ,
DeltaH degrees , and DeltaS degrees ) revealed that the biosorption of considered
metal ions was feasible, spontaneous and exothermic at 25-45 degrees C. The SEM
showed porous morphology which greatly helps in the biosorption of heavy metals.
The Fourier transform infrared spectrophotometer (FTIR) and X-rays Photon
Spectroscopy (XPS) data spectra indicated that the functional groups
predominately involved in the biosorption were C-N, -OH, COO-, -CH, C=C, C=S and
C-. These results shows that immobilized algal cells in alginate beads could
potentially enhance the biosorption of considered metal ions than freely
suspended cells. Furthermore, the biosorbent has significantly removed heavy
metals from industrial wastewater at the optimized condition.
PMID- 29345547
TI - Are Current Physical Match Performance Metrics in Elite Soccer Fit for Purpose or
Is the Adoption of an Integrated Approach Needed?
AB - Time-motion analysis is a valuable data-collection technique used to quantify the
physical match performance of elite soccer players. For over 40 years,
researchers have adopted a "traditional" approach when evaluating match demands
by simply reporting the distance covered or time spent along a motion continuum
of walking through to sprinting. This methodology quantifies physical metrics in
isolation without integrating other factors, and this ultimately leads to a 1
dimensional insight into match performance. Thus, this commentary proposes a
novel "integrated" approach that focuses on a sensitive physical metric such as
high-intensity running but contextualizes this in relation to key tactical
activities for each position and collectively for the team. In the example
presented, the integrated model clearly unveils the unique high-intensity profile
that exists due to distinct tactical roles, rather than 1-dimensional "blind"
distances produced by traditional models. Intuitively, this innovative concept
may aid coaches' understanding of the physical performance in relation to the
tactical roles and instructions given to the players. In addition, it will enable
practitioners to effectively translate match metrics into training and testing
protocols. This innovative model may well aid advances in other team sports that
incorporate similar intermittent movements with tactical purpose. Evidence of the
merits and application of this new concept is needed before the scientific
community accepts this model as it may well add complexity to an area that
conceivably needs simplicity.
PMID- 29345548
TI - ABI: The goal line is in sight.
PMID- 29345549
TI - Veterinary Medical Students' Motivations for Exercise.
AB - The Centers for Disease Control (CDC) declares exercise to be one of the most
important activities one can do to improve health. The benefits of exercise are
well documented and include both physiologic and psychological health. Given the
current landscape of wellness issues in veterinary medical education, it is
necessary that students engage in exercise activities to manage stress and
increase overall health. Therefore, to develop targeted interventions with the
greatest likelihood for success, it is first necessary to understand what
motivates veterinary medical students to exercise given their unique situational
and environmental factors. This study is the first to explore this issue
systematically in veterinary medical education, thus it is the authors' hope that
the findings from this research will help identify exercise-related wellness
interventions that could be implemented in veterinary medical schools.
PMID- 29345550
TI - An Anatomy Pre-Course Predicts Student Performance in a Professional Veterinary
Anatomy Curriculum.
AB - Little to no correlation has been identified between previous related
undergraduate coursework or outcomes on standardized tests and performance in a
veterinary curriculum, including anatomy coursework. Therefore, a relatively
simplistic method to predict student performance before entrance would be
advantageous to many. The purpose of this study was to evaluate whether there is
a correlation between performance in a veterinary anatomy pre-course and
subsequent performance within a professional anatomy curriculum. Incoming first
year veterinary students at the Louisiana State University School of Veterinary
Medicine were asked to participate in a free weeklong pre-course, before the
start of the semester. The pre-course covered the musculoskeletal anatomy of the
canine thoracic limb using dissection-based methods. Student performance, as
evaluated by test grades in the pre-course, did indeed correlate with test grades
in professional veterinary anatomy courses. A significant and positive
correlation was identified between pre-course final exam performance and
performance on examinations in each of 3 professional anatomy courses.
Qualitative analyses of student comments pertaining to their experience within
the pre-course indicated differences in the perceived benefits of the pre-course
between high-, middle-, and low-performing students. These varied perceptions may
provide predictive feedback as well as guidance for supporting lower performing
students. Together, these results indicate that performance in a weeklong pre
course covering only a small portion of canine anatomy is a strong predictor of
performance within a professional anatomy curriculum. In addition, the pre-course
differentially affected student perceptions of their learning experience.
PMID- 29345551
TI - Quantifying Novice and Expert Differences in Visual Diagnostic Reasoning in
Veterinary Pathology Using Eye-Tracking Technology.
AB - Visual diagnostic reasoning is the cognitive process by which pathologists reach
a diagnosis based on visual stimuli (cytologic, histopathologic, or gross
imagery). Currently, there is little to no literature examining visual reasoning
in veterinary pathology. The objective of the study was to use eye tracking to
establish baseline quantitative and qualitative differences between the visual
reasoning processes of novice and expert veterinary pathologists viewing cytology
specimens. Novice and expert participants were each shown 10 cytology images and
asked to formulate a diagnosis while wearing eye-tracking equipment (10 slides)
and while concurrently verbalizing their thought processes using the think-aloud
protocol (5 slides). Compared to novices, experts demonstrated significantly
higher diagnostic accuracy (p <.017), shorter time to diagnosis (p <.017), and a
higher percentage of time spent viewing areas of diagnostic interest (p <.017).
Experts elicited more key diagnostic features in the think-aloud protocol and had
more efficient patterns of eye movement. These findings suggest that experts'
fast time to diagnosis, efficient eye-movement patterns, and preference for
viewing areas of interest supports system 1 (pattern-recognition) reasoning and
script-inductive knowledge structures with system 2 (analytic) reasoning to
verify their diagnosis.
PMID- 29345552
TI - The Effect of Preceding Race Efforts on Pacing and Short-Track Speed Skating
Performance.
AB - PURPOSE: To examine whether preceding high-intensity race efforts in a
competitive weekend affect pacing behavior and performance in elite short-track
speed skaters. METHODS: Finishing and intermediate lap times were gathered from
500-, 1000-, and 1500-m short-track speed skating world cups during the seasons
2011-2016. The effect of preceding races on pacing behavior and performance was
explored using 2 studies. Study I: The effect of competing in extra races due to
the repechage (Rep) system, leading to an increased number of high-intensity race
efforts prior to the subsequent main tournament race, was explored (500-m, n =
32; 1000-m, n = 34; and 1500-m, n = 47). Study II: The performance of skaters
over the tournament days was evaluated (500-m, n = 129; 1000-m, n = 54; and 1500
m, n = 114). For both analytic approaches, a 2-way repeated-measures analysis of
variance was used to assess differences in pacing and performance within skaters
over the races. RESULTS: An additional number of preceding high-intensity race
efforts due to the Rep system reduced the qualification percentage in the first
main tournament race for the next stage of competition in all events (500-m,
direct qualification = 57.3%, Rep = 25.0%; 1000-m, direct = 44.2%, Rep = 28.3%;
and 1500-m, direct = 27.1%, Rep = 18.2%) and led to a decreased pace in the
initial 2 laps of the 500-m event. By contrast, tournament day (Saturday vs
Sunday) only affected the pacing behavior of female skaters during the 1500-m
event. CONCLUSION: High-intensity race efforts earlier in the day affected pacing
and performance of elite skaters, whereas the effect of high-intensity race
efforts from the previous day seemed to be only marginal.
PMID- 29345553
TI - Quality and Variability of Patient Directions in Electronic Prescriptions in the
Ambulatory Care Setting.
AB - BACKGROUND: The prescriber's directions to the patient (Sig) are one of the most
quality-sensitive components of a prescription order. Owing to their free-text
format, the Sig data that are transmitted in electronic prescriptions (e
prescriptions) have the potential to produce interpretation challenges at
receiving pharmacies that may threaten patient safety and also negatively affect
medication labeling and patient counseling. Ensuring that all data transmitted in
the e-prescription are complete and unambiguous is essential for minimizing
disruptions in workflow at prescribers' offices and receiving pharmacies and
optimizing the safety and effectiveness of patient care. OBJECTIVES: To (a)
assess the quality and variability of free-text Sig strings in ambulatory e
prescriptions and (b) propose best-practice recommendations to improve the use of
this quality-sensitive field. METHODS: A retrospective qualitative analysis was
performed on a nationally representative sample of 25,000 e-prescriptions issued
by 22,152 community-based prescribers across the United States using 501
electronic health records (EHRs) or e-prescribing software applications. The
content of Sig text strings in e-prescriptions was classified according to a Sig
classification scheme developed with guidance from an expert advisory panel. The
Sig text strings were also analyzed for quality-related events (QREs). For
purposes of this analysis, QREs were defined as Sig text content that could
impair accurate and unambiguous interpretation by staff at receiving pharmacies.
RESULTS: A total of 3,797 unique Sig concepts were identified in the 25,000 Sig
text strings analyzed; more than 50% of all Sigs could be categorized into 25
unique Sig concepts. Even Sig strings that expressed apparently simple and
straightforward concepts displayed substantial variability; for example, the
sample contained 832 permutations of words and phrases used to convey the Sig
concept of "Take 1 tablet by mouth once daily." Approximately 10% of Sigs
contained QREs that could pose patient safety risks or workflow disruptions that
could necessitate pharmacist callbacks to prescribers for clarification or other
manual interventions. CONCLUSIONS: The quality of free-text patient directions in
e-prescriptions can vary dramatically. However, more than half of all patient
directions sent in the ambulatory setting can be categorized into only 25 Sig
concepts. This suggests an immediate, practical opportunity to improve patient
safety and workflow efficiency for both prescribers and pharmacies.
Recommendations include implementing enhancements to Sig creation tools in e
prescribing and EHR software applications, adoption of the Structured and
Codified Sig format supported by the current national e-prescribing standard, and
improved usability testing and end-user training for generating complete and
unambiguous patient directions. Such quality improvements are essential for
optimizing the safety and effectiveness of patient care as well as for minimizing
workflow disruptions to both prescribers and pharmacies. DISCLOSURES: This
research received no specific grant from any funding agency in the public,
commercial, or not-for-profit sectors. Yang, Ward-Charlerie, Dhavle, and Green
are employed by Surescripts. Rupp reported receiving consulting fees from
Surescripts during the conduct of this study. No other disclosures were reported.
The content in this article is solely the responsibility of the authors and does
not necessarily represent the official views of Surescripts and Midwestern
University or any of the affiliated institutions of the authors. Study concept
and design were contributed by all the authors. Yang and Ward-Charlerie collected
the data, and data interpretion was performed by Yang, Ward-Charlerie and Dhavle.
The manuscript was primarily written by Yang, along with Dhavle and Green, and
revised by Yang, Dhavle, Rupp, and Green.
PMID- 29345554
TI - Letter to the editor concerning the article "Relationship between school rhythm
and physical activity in adolescents: the HELENA study" by Vanhelst et al.
(2017).
AB - Recently Vanhelst et al. published a study on the relationship between school
rhythm and physical activity patterns in European adolescents in the Journal of
Sports Sciences. With this Letter to the Editor we would like to comment on the
practical implementation and further perspectives of the study.
PMID- 29345555
TI - The Preparation Period in Basketball: Training Load and Neuromuscular
Adaptations.
AB - PURPOSE: To investigate the effect of the preparation period on neuromuscular
characteristics of 12 professional (PRO) and 16 semiprofessional (SEMIPRO)
basketball players and relationships between training-load indices and changes in
neuromuscular physical performance. METHODS: Before and after the preparation
period, players underwent a countermovement jump (CMJ) test followed by a
repeated change-of-direction (COD) test consisting of 4 levels with increasing
intensities. The peripheral neuromuscular functions of the knee extensors (peak
torque [PT]) were measured using electrical stimulations after each level (PT1,
PT2, PT3, and PT4). Furthermore, PT Max (the highest value of PT) and PT Dec (PT
decrement from PT Max to PT4) were calculated. RESULTS: Trivial to small (effect
size [ES] = -0.17 to 0.46) improvements were found in CMJ variables, regardless
of competitive level. After the preparation period, peripheral fatigue induced by
a COD test was similarly reduced in both PRO (PT Dec: from 27.8% [21.3%] to 11.4%
[13.7%]; ES = -0.71; 90% confidence interval [CI], +/-0.30) and SEMIPRO (PT Dec:
from 26.1% [21.9%] to 10.2% [8.2%]; ES = -0.69; 90% CI, +/-0.32). Moderate to
large relationships were found between session rating of perceived exertion
training load and changes in peak power output (PPO) measured during the CMJs (rs
[90% confidence interval]: PPOabs, -.46 [+/-.26]; PPOrel, -.53 [+/-.23]) and in
some PTs measured during the COD test (PT1, -.45 [+/-.26]; PT2, -.44 [+/-.26];
PT3, -.40 [+/-.27]; and PT Max, -.38 [+/-.28]). CONCLUSIONS: The preparation
period induced minimal changes in the CMJ, while the ability to sustain repeated
COD efforts was improved. Reaching high session rating of perceived exertion
training loads might partially and negatively affect the ability to produce
strength and power.
PMID- 29345556
TI - Positional Differences in Elite Basketball: Selecting Appropriate Training-Load
Measures.
AB - PURPOSE: To study the structure of interrelationships among external-training
load measures and how these vary among different positions in elite basketball.
METHODS: Eight external variables of jumping (JUMP), acceleration (ACC),
deceleration (DEC), and change of direction (COD) and 2 internal-load variables
(rating of perceived exertion [RPE] and session RPE) were collected from 13
professional players with 300 session records. Three playing positions were
considered: guards (n = 4), forwards (n = 4), and centers (n = 5). High and total
external variables (hJUMP and tJUMP, hACC and tACC, hDEC and tDEC, and hCOD and
tCOD) were used for the principal-component analysis. Extraction criteria were
set at an eigenvalue of greater than 1. Varimax rotation mode was used to extract
multiple principal components. RESULTS: The analysis showed that all positions
had 2 or 3 principal components (explaining almost all of the variance), but the
configuration of each factor was different: tACC, tDEC, tCOD, and hJUMP for
centers; hACC, tACC, tCOD, and hJUMP for guards; and tACC, hDEC, tDEC, hCOD, and
tCOD for forwards are specifically demanded in training sessions, and therefore
these variables must be prioritized in load monitoring. Furthermore, for all
playing positions, RPE and session RPE have high correlation with the total
amount of ACC, DEC, and COD. This would suggest that although players perform the
same training tasks, the demands of each position can vary. CONCLUSION: A
particular combination of external-load measures is required to describe the
training load of each playing position, especially to better understand internal
responses among players.
PMID- 29345557
TI - Co-registration of cone beam CT and preoperative MRI for improved accuracy of
electrode localization following cochlear implantation.
AB - OBJECTIVES: To investigate the clinical usefulness and practicality of co
registration of Cone Beam CT (CBCT) with preoperative Magnetic Resonance Imaging
(MRI) for intracochlear localization of electrodes after cochlear implantation.
METHODS: Images of 20 adult patients who underwent CBCT after implantation were
co-registered with preoperative MRI scans. Time taken for co-registration was
recorded. The images were analysed by clinicians of varying levels of expertise
to determine electrode position and ease of interpretation. RESULTS: After a
short learning curve, the average co-registration time was 10.78 minutes (StdDev
2.37). All clinicians found the co-registered images easier to interpret than
CBCT alone. The mean concordance of CBCT vs. co-registered image analysis between
consultant otologists was 60% (17-100%) and 86% (60-100%), respectively. The
sensitivity and specificity for CBCT to identify Scala Vestibuli insertion or
translocation was 100 and 75%, respectively. The negative predictive value was
100%. DISCUSSION: CBCT should be performed following adult cochlear implantation
for audit and quality control of surgical technique. If SV insertion or
translocation is suspected, co-registration with preoperative MRI should be
performed to enable easier analysis. There will be a learning curve for this
process in terms of both the co-registration and the interpretation of images by
clinicians.
PMID- 29345558
TI - Activation of NADPH Oxidase by beta-Glucan from Phellinus baumii (Agaricomycetes)
in RAW 264.7 Cells.
AB - Production of oxygen-derived free radicals in phagocytes is important in
preventing bacterial and fungal infections. Among free radicals, superoxide
anions are a typical reactive oxygen species secreted by macrophages and
neutrophils. NADPH oxidase (NOX) is a key producer of superoxide anions in these
cells. beta-glucans from mushrooms modulate the immune system by binding with the
dectin-1 receptor on macrophages. Dectin-1 functions as a pattern recognition
receptor that recognizes the pathogen-associated molecular pattern of beta
glucans. During dectin-1 signaling, NOX functions in the activated macrophages to
produce ROS, which are critical in antimicrobial host defense. In this study, NOX
activation was measured using a lucigenin chemiluminescence assay in RAW 264.7
murine macrophages treated for 1 hour with a beta-glucan fraction from Phellinus
baumii (BGF; 10, 100, 500, and 1000 MUg/mL) in the absence or presence of phorbol
12-myristate 13-acetate (PMA) or lipopolysaccharide (LPS). NOX was activated at
BGF concentrations exceeding 10 MUg/mL. BGF in the presence of PMA or LPS
activated the enzyme more than treatment with PMA or LPS alone. In the presence
of the NOX inhibitor diphenyleneiodonium, BGF still activated NOX. When
macrophages were treated with BGF and Staphylococcus aureus, bacterial viability
was reduced in a concentration-dependent manner, possibly as a result of
increased phagocytosis and oxygen radical production by the activated NOX. These
results demonstrate that BGF is a potent stimulator of NOX in macrophages and
augments macrophage-mediated phagocytosis and NOX activity.
PMID- 29345559
TI - Antioxidant and Genotoxic Properties of Hispidin Isolated from the Velvet-Top
Mushroom, Phaeolus schweinitzii (Agaricomycetes).
AB - Antioxidant and genotoxic properties of hispidin isolated from the Phaeolus
schweinitzii mushroom were evaluated with various assays. Hispidin demonstrated
strong free radical scavenging, oxygen radical absorbance capacity, and ferric
reducing antioxidant power; in all applied assays, hispidin exhibited antioxidant
capacity similar to or higher than that of the reference antioxidant Trolox.
Genotoxic activity of hispidin was assessed using different end points:
chromosome aberrations, micronuclei, sister chromatid exchanges, and primary DNA
damage (detected by the comet assay) in human lymphocytes in vitro, and gene
mutations in the Salmonella/microsome test. Hispidin did not increase the
frequency of chromosome aberrations, micronuclei, or primary DNA damage in human
lymphocytes in vitro and did not produce reverse mutation in bacterial cells.
However, we identified in human lymphocytes a statistically significant dose
dependent increase in sister chromatid exchange frequency and a decrease in
replication index and nuclear division index values.
PMID- 29345560
TI - Shiitake Culinary-Medicinal Mushroom, Lentinus edodes (Agaricomycetes): A Species
with Antioxidant, Immunomodulatory, and Hepatoprotective Activities in
Hypercholesterolemic Rats.
AB - Lentinus edodes is a culinary-medicinal mushroom that has an established history
of use in Asian therapies. The mushroom offers well-documented beneficial health
effects such as antihypercholesterolemic, antitumor, and antibacterial
activities. In this study, dried powder of L. edodes fruiting bodies was used to
evaluate immunomodulatory, hepatoprotective, and antioxidant effects in
hypercholesterolemic rats. Albino rats (n = 24) were divided into 3 groups: the
control (CON) group, the hypercholesterolemia-only group (HCG), and the L. edodes
group (LEG). Hypercholesterolemia was induced in rats in the HCG and LEG by
feeding cholesterol and cholic acid in a chow maintenance diet (CMD) for 24 days.
The CON group was fed the CMD throughout the experiment. The HCG continued on the
high-cholesterol diet without any L. edodes supplement. The LEG was fed the high
cholesterol diet supplemented with L. edodes for an additional 42 days. Various
biological health biomarkers, such as total antioxidant capacity, total oxidant
status, arylesterase, paraoxonase activity, and liver enzymes in serum were
studied to evaluate antioxidant and hepatoprotective responses. Cell-mediated
immunity was evaluated in each group through a delayed type of hypersensitivity
reaction. The total oxidant status decreased significantly (P <= 0.05) after
administration of L. edodes in the diet. The cell-mediated immune response
significantly increased (P <= 0.05) in the LEG. The significant decrease in liver
enzymes supports the hepatoprotective effect of L. edodes. In conclusion, the
results show the immunomodulatory, hepatoprotective, and antioxidant activities
of L. edodes supplementation in hypercholesterolemic rats.
PMID- 29345561
TI - Characterization of the Effects of the Shiitake Culinary-Medicinal Mushroom,
Lentinus edodes (Agaricomycetes), on Severe Gestational Diabetes Mellitus in
Rats.
AB - This study evaluated the protective effect of Lentinus edodes in rats with
streptozotocin-induced gestational diabetes mellitus (STZ-GDM) when administered
orally. The rats received from the 1st to the 19th day of gestation daily doses
of 100 or 200 mg/kg of lyophilized and reconstituted L. edodes; the animals in
the saline control group and diabetic control group received a saline solution
(DS). Gestational diabetes mellitus was induced by streptozotocin (80 mg/kg,
administered intraperitoneally) on the fourth day of pregnancy; blood glucose >
180 mg/dL was considered to indicate STZ-GDM. L. edodes reduced catalase in
plasma. We also observed reduced glucose in plasma, urea, triglycerides, and
aspartate aminotransferase. There was a decrease in preimplantation loss when
compared with the DS group. The doses of L. edodes used here had a protective
effect on the preimplantation parameters in STZGDM. However, the mushroom was not
able to reverse the deleterious effects caused by streptozotocin throughout the
evolution of pregnancy.
PMID- 29345562
TI - Ethanolic Extract of the Golden Oyster Mushroom, Pleurotus citrinopileatus
(Agaricomycetes), Alleviates Metabolic Syndrome in Diet-Induced Obese Mice.
AB - Pleurotus citrinopileatus is an edible medicinal mushroom rich in biomolecules
and thus has a high potential for use in formulating pharmaceutical and
nutraceutical products. To test its effect on body weight and glucose control, we
generated diet-induced obese (DIO) C57BL/6J male mice by feeding the mice a high
fat diet (60% fat) for 8 weeks and treating them with an ethanolic P.
citrinopileatus extract (PCE) at either 200 or 500 mg/kg body weight for 12
additional weeks. The results showed that PCE significantly inhibited high-fat
diet-induced weight gain, fat accumulation, and glucose intolerance in the DIO
mice. Moreover, the PCE had a beneficial effect on liver and kidney function. On
the basis of these results, we conclude that PCE is effective in the treatment of
metabolic syndrome and thus could be a good candidate for use in future
pharmaceutical or nutraceutical applications.
PMID- 29345563
TI - Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), as a
Cardioprotectant in an Oxygen-Deficient Environment.
AB - Imbalanced oxygen availability is detrimental to normal cell function. Oxygen
sensitive cells such as cardiomyoblasts experience severe irreversible
pathophysiological damage under conditions of reduced oxygen availability, such
as hypoxia. A number of natural therapeutic agents have been explored for their
potential cytoprotective effects, of which medicinal mushrooms are an important
source. Ganoderma lucidum, commonly known as lingzhi, is one such mushroom that
has been elaborately studied for its potential pharmacological properties. In
this study, aqueous and alcoholic extracts of a natural Himalayan variety of G.
lucidum were evaluated for their efficiency as remedial agents in treating
hypoxic injury to H9c2 cardiomyoblasts. The alcoholic extract of G. lucidum
effectively restored cellular viability at a concentration of 600 MUg/mL and
aided in maintaining cellular redox balance under hypoxia. Substantial reduction
in caspase-3 and -7 activation was observed with fluorescent-activated cell
sorting. Alcoholic extract of G. lucidum minimized oxidative stress as indicated
by measuring reactive oxygen species, lipid peroxidation, and reduced glutathione
to-oxidized glutathione ratio, and also by determining changes in hypoxia
inducible factor 1alpha and associated genes. To ascertain these positive
outcomes of administration of G. lucidum extracts, certain phytoconstituents
(nucleobases and flavonoids) were identified using high-performance thin-layer
chromatography; antioxidant potential was also evaluated. Results indicated that
both extracts contained notable quantities of nucleobases and flavonoids. The
extracts also effected high free radical scavenging activities.
PMID- 29345564
TI - Profiles of Little-Known Medicinal Polypores: Earliella scabrosa
(Agaricomycetes).
AB - The purpose of this study was to comprehensively characterize a little-known
polypore that has recently been found to possess anticancer activity and thus can
also be used in targeted cancer therapy. Earliella scabrosa is a polypore with
pantropical distribution and can be found in rainforests in both the Eastern and
Western Hemispheres. Some reports have described its antioxidant properties and
free radical scavenging ability. Moreover, isocoumarin, which has been
successfully used in targeted cancer therapy, was found in extracts of this
fungus. We recommend further research of E. scabrosa so that more details of its
health benefits could be used in mycotherapy.
PMID- 29345565
TI - Identification of Reference Genes and Analysis of Heat Shock Protein Gene
Expression in Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum, after
Exposure to Heat Stress.
AB - Ganoderma lucidum has been considered an emerging model species for studying how
environmental factors regulate the growth, development, and secondary metabolism
of Basidiomycetes. Heat stress, which is one of the most important environmental
abiotic stresses, seriously affects the growth, development, and yield of
microorganisms. Understanding the response to heat stress has gradually become a
hotspot in microorganism research. But suitable reference genes for expression
analysis under heat stress have not been reported in G. lucidum. In this study,
we systematically identified 11 candidate reference genes that were measured
using reverse transcriptase quantitative polymerase chain reaction, and the gene
expression stability was analyzed under heat stress conditions using geNorm and
NormFinder. The results show that 5 reference genes-CYP and TIF, followed by
UCE2, ACTIN, and UBQ1-are the most stable genes under our experimental
conditions. Moreover, the relative expression levels of 3 heat stress response
genes (hsp17.4, hsp70, and hsp90) were analyzed under heat stress conditions with
different normalization strategies. The results show that use of a gene with
unstable expression (SAND) as the reference gene leads to biased data and
misinterpretations of the target gene expression level under heat stress.
PMID- 29345566
TI - Productivity, Physicochemical Changes, and Antioxidant Activity of Shiitake
Culinary-Medicinal Mushroom Lentinus edodes (Agaricomycetes) Cultivated on
Lignocellulosic Residues.
AB - The effects of substrate and strain on productivity, physicochemical
characteristics, and compounds with antioxidant activity were evaluated in
basidiomes of the shiitake mushroom, Lentinus edodes. Strains IE-245 and IE-256
and the substrates oak wood shavings (OW), sorghum stubble (SS), and sugar cane
bagasse (SC) were used. Productivity was evaluated by measuring biological
efficiency (BE), production rate (PR), and yield. Total sugars, total soluble
solids, pH, titratable acidity, color parameters, total phenolics, flavonoids,
ascorbic acid, and antioxidant activity of the basidiomes were measured. BE, PR
and yield were higher with the combination IE-256/SS, at 103.71%, 1.32%, and
34.57%, respectively. The largest amount of total sugars (17.61 mg glucose . g-1
dry weight) was found with combination IE-256/SS. Variation was observed in
basidiome color; the lowest luminosity (L*) value (darkest color) was found in
the IE-256 strain on the OW substrate (L* = 30.45), whereas that of the IE-245
strain on the SC substrate was the lightest in color (L* = 57.00). The largest
amounts of total phenolics were recorded in the IE-256 strain on the OW (6.50 mg
gallic acid equivalents [GAE] . g-1 dry weight) and the SS substrates (5.85 mg
GAE . g-1 dry weight). The best antioxidant activity was obtained with IE-256
0.80, 0.65, and 0.59 MUmol Trolox equivalents . g dry weight-1-on the OW, SC, and
SS substrates, respectively. Based on the values of BE, PR, and yield, IE-256/SS
was the most productive. Substrate and strain, and their interactions, influenced
the physicochemical characteristics of the basidiomes and the amounts of
compounds with antioxidant activity they contained.
PMID- 29345567
TI - Proteomic Analysis of Vernalization Responsive Proteins in Winter Wheat Jing841.
AB - BACKGROUND: Vernalization is one of the pivotal ways for plants to flower. The
twodimensional gel electrophoresis (2-DE) and matrix-assisted laser
desorption/ionization time-offlight/ time-of-flight mass spectrometry (MALDI
TOF/TOF MS) were applied to analyze the changes in protein expression profiles in
responding to vernalization in leaves of wheat seedling before (0d) and after
(30d) of vernalization. OBJECTIVE: The main objective of this study was to
analyze the vernalization-responsive proteins in winter wheat after
vernalization. METHODS: Winter wheat seedling leaf proteins were extracted by
phenol extraction coupled with ammonium acetate in methanol. 2-DE was conducted
according to procedures described in the manual given by the GE manufacture. The
selected protein spots were identified by MALDITOF/ TOF MS. Gene ontology (GO)
classification was applied to classify the functions of the differentially
expressed proteins. Pathway enrichment analysis identified significantly enriched
metabolic pathways or signal transduction pathways relative to the whole proteins
background. RESULTS: The results of 2-DE and MALDI-TOF/TOF MS showed that among
the 65 differentially expressed proteins that were successfully identified under
vernalization, 30 were up-regulated whereas 35 were down-regulated after
vernalization, respectively. These vernalization-responsive proteins were found
to play roles in carbohydrate metabolism, protein metabolism, photosynthesis,
defense and stress-resistance and may therefore participate in many biological
processes in responding to vernalization. The enhanced accumulation of proteins
after vernalization, such as thiamine thiazole synthase, late embryogenesis
abundant protein, and glutathione-S-transferase, probably play vital roles in the
mechanisms underlying vernalization response in wheat. CONCLUSION: Our results
indicated these vernalization-responsive proteins were found to be involved in
protein metabolism, carbohydrate metabolism, photosynthesis, and stress
resistance/ defense. The responses of plants to low temperature were very
complex, involving in a wide range of cellular pathways for signal transduction,
gene regulation, protein modifications, and metabolic regulation. Studying on
wheat proteomic profiles in response to vernalization can improve our
understanding the molecular mechanisms underlying vernalization in cereals. The
results obtained in this study have provided a novel insight into the mechanisms
underlying vernalization in cereal crops.
PMID- 29345568
TI - Surface-bioengineered Gold Nanoparticles for Biomedical Applications.
AB - The conjugation of gold nanoparticles (AuNPs) with biomolecules could create many
outstanding biofunctions for the surface-functionalized nanoparticles and extend
their biomedical applications. In this review, we summarize the recent advances
in the surface bioengineering of AuNPs with biomolecules, such as DNA, proteins,
peptides, and biopolymers, in which the details on the structure, functions, and
properties of surface- bioengineered AuNPs are discussed. In addition, the
surface-biofunctionalization of AuNPs for biomedical applications like
biosensing, bioimaging, drug delivery, and tissue engineering are introduced. It
is expected that this work will be very helpful for readers to understand the
surface functionalization and engineering techniques for various metallic
nanoparticles and design novel biomaterials for biomedical applications.
PMID- 29345569
TI - A Complex Scenario and Underestimated Challenge: The Tumor Microenvironment, ER
Stress, and Cancer Treatment.
AB - The paradoxical role of ER stress in malignant diseases is only just being
unraveled and remains incompletely understood. A particular challenge is the
complex interplay between spaciotemporal and locoregional microenvironmental
constraints in solid tumors and stress responses upon treatment; thus, the
potential for new combinatorial therapeutic options to foster the coincidence of
ER stress-related deadly events is likely to be underestimated. Without claiming
this review to be complete, we present a comprehensive overview of the signaling
mechanisms associated with the unfolded protein response (UPR) and the molecular
link to cell survival and death mechanisms. We (i) delineate the mechanistic
scenario and outcome of the UPR; (ii) discuss the role of ER stress in cancer
development and progression; (iii) highlight the impact of various environmental
conditions and stress stimuli, such as nutrient limitation and tumor hypoxia, in
this context; and (iv) attempt to shed some light on the putative link between
DNA damage, irradiation, and ER stress to emphasize the potential of therapeutic
targeting of ER stress pathways for combined cancer treatments.
PMID- 29345570
TI - The role of AMPK/mTOR modulators in therapy of acute myeloid leukemia.
AB - Differentiation therapy of acute promyelocytic leukemia with all-trans retinoic
acid represents the most successful pharmacological therapy of acute myeloid
leukemia (AML). Numerous studies demonstrate that drugs that inhibit mechanistic
target of rapamycin (mTOR) and activate AMP-kinase (AMPK) have beneficial effects
in promoting differentiation and blocking proliferation of AML. Most of these
drugs are already in use for other purposes; rapalogs as immunosuppressants,
biguanides as oral antidiabetics, and 5-amino-4-imidazolecarboxamide
ribonucleoside (AICAr, acadesine) as an exercise mimetic. Although most of these
pharmacological modulators have been widely used for decades, their mechanism of
action is only partially understood. In this review, we summarize the role of
AMPK and mTOR in hematological malignancies and discuss the possible role of
pharmacological modulators in proliferation and differentiation of leukemia
cells.
PMID- 29345571
TI - Targeting Cytosolic Phospholipase A2alpha for Novel Anti-Inflammatory Agents.
AB - Group IV cytosolic phospholipase A2 (cPLA2alpha) plays a critical role in
inflammatory processes. It produces arachidonic acid which is the main source of
the pro-inflammatory eicosanoids mediators that are important in innate immune
system. In some cases, these proinflammatory mediators cause damages to the host
tissues and therefore promote autoimmune diseases. Consequently, development of
potent inhibitors against cPLA2alpha could improve the therapy of inflammatory
diseases. In the last two decades, intense efforts have been done to find potent
cPLA2alpha inhibitors. Several scaffolds have been developed with the use of
structure activity relationship (SAR) studies, and potent inhibitors have been
obtained. The poor absorption of these compounds from intestine was the main
challenge for clinical application. This review illustrates the search for
cPLA2alpha inhibitors, their SAR studies and biological effects.
PMID- 29345572
TI - Breaking the DNA damage response via serine/threonine kinase inhibitors to
improve cancer treatment.
AB - Multiple, both endogenous and exogenous, sources may induce DNA damage and DNA
replication stress. Cells have developed DNA damage response (DDR) signaling
pathways to maintain genomic stability and effectively detect and repair DNA
lesions. Serine/threonine kinases such as Ataxia-telangiectasia mutated (ATM) and
Ataxia-telangiectasia and Rad3-Related (ATR) are the major regulators of DDR,
since after sensing stalled DNA replication forks, DNA double- or single-strand
breaks, may directly phosphorylate and activate their downstream targets, that
play a key role in DNA repair, cell cycle arrest and apoptotic cell death.
Interestingly, key components of DDR signaling networks may constitute an
attractive targets for anti-cancer therapy through two distinct potential
approaches: as a chemo- and radiosensitizers to enhance the effectiveness of
currently used genotoxic treatment or as a single agents to exploit defects in
DDR in cancer cells via synthetic lethal approach. Moreover, the newest data
reported that serine/threonine protein kinase R (PKR)-like endoplasmic reticulum
kinase (PERK) is also closely associated with cancer development and progression.
Thereby, utilization of small-molecule, serine/threonine kinase inhibitors may
provide a novel, groundbreaking, anti-cancer treatment strategy. Currently, a
range of potent, highly-selective toward ATM, ATR and PERK inhibitors has been
discovered, but after foregoing study, additional investigations are necessary
for their future clinical use.
PMID- 29345573
TI - Precision Medicine: Update on Diagnosis and Therapeutic Strategies of
Hepatocellular Carcinoma.
AB - Recent advances in multiple omics technologies and the advent of massively
parallel sequencing provide technical supports for the implementation of
precision medicine. The precision medicine emphasizes that heterogeneous diseases
can be well classified into more precise subtypes by the powerful detection
methods and integration of clinical features, so that the clinicians should
develop more accurate diagnosis and therapeutic strategies for the disease
subtype population in an effort to maximize the efficacy and minimize the
unnecessary side effects. Oncology is at the forefront of precision medicine, as
malignant tumors have significant heterogeneity and are among the leading causes
of death nationally and worldwide. The incidence and mortality of Hepatocellular
Carcinoma (HCC), a kind of extraordinarily heterogeneous malignancy, have been
increasing worldwide, making it a major public health concern. Such heterogeneity
affects key signaling pathways, driving phenotypic variation, influences tumor
evolution, and poses severe challenges to HCC treatment. The application of
precision medicine will have certain impact on HCC diagnosis and treatment
strategies. Herein, we summarize the updates and challenges in high-risk
population screening, prevention, diagnosis, staging and therapy of HCC under the
concept of precision medicine.
PMID- 29345574
TI - Role of CD73 in Disease: Promising Prognostic Indicator and Therapeutic Target.
AB - CD73, also known as ecto-5'-nucleotidase (eN, NT5E, EC3.13.5), is the
ratelimiting enzyme for adenosine generation and is expressed on multiple cells.
Its expression is significantly influenced by hypoxia and inflammatory factors.
During inflammation, CD73 protects endothelial barrier function and inhibits
leukocyte trafficking. CD73 also promotes M2 macrophages (anti-inflammatory
phenotype). In addition, CD73 is expressed on Treg cells and mediates immune
suppression through adenosine. CD73 serves as an essential regulator for the
immunity and inflammation. Its expression is related to many diseases, such as
autoimmune diseases, ischemia-reperfusion injuries, arterial calcifications, and
atherosclerosis. CD73 is overexpressed in many cancers. Its expression is
positively associated with tumor growth, metastasis, angiogenesis, poor prognosis
and resistance to chemotherapy. Thus, CD73 may be used for prognostic indicator
and therapeutic target in diseases such as cancers.
PMID- 29345575
TI - Recent progress in chemosensors using aldehyde-bearing fluorophores for detection
of specific analytes and its bioimaging.
AB - In recent years, aldehyde-appended fluorescence probes are paid more and more
attention by researchers. The fluorescent biological imaging provided many new
applications today, which is often used for cell and tissue imaging in biomedical
research. Meanwhile, the nucleophilic mechanism is a very simple and convenient
procedure for the preparation of aldehyde-sensing probes. This tutorial review
focuses on aldehyde-bearing chemosensors based on nucleophilic addition mechanism
with biological applications.
PMID- 29345576
TI - Radiotracers for Amyloid Imaging in Neurodegenerative Disease: State-of-the-Art
and Novel Concepts.
AB - The pathological accumulation of different peptides is the common base of many
neurodegenerative processes, such as Alzheimer's disease (AD). AD is
characterized by amyloid deposits which may cause alterations in
neurotransmission, activation of inflammatory mechanisms, neuronal death and
cerebral atrophy. Diagnosis in vivo is challenging as the criteria rely mainly on
clinical manifestations, which become evident only in a late stage of the
disease. While AD can currently be definitively confirmed by postmortem
histopathologic examination, in vivo imaging may improve the clinician's ability
to identify AD at the earliest stage. In this regard, the detection of cerebral
amyloid plaques with positron emission tomography (PET) is likely to improve
diagnosis and allow for a prompt start of an effective therapy. Many PET imaging
probes for AD-specific pathological modifications have been developed and proved
effective in detecting amyloid deposits in vivo. We here review the current
knowledge on PET imaging in the detection of amyloid deposits and their
application in the diagnosis of AD.
PMID- 29345577
TI - Probiotics and Paraprobiotics in Viral Infection: Clinical Application and
Effects on the Innate and Acquired Immune Systems.
AB - Recently, the risk of viral infection has dramatically increased owing to changes
in human ecology such as global warming and an increased geographical movement of
people and goods. However, the efficacy of vaccines and remedies for infectious
diseases is limited by the high mutation rates of viruses, especially, RNA
viruses. Here, we comprehensively review the effectiveness of several probiotics
and paraprobiotics (sterilized probiotics) for the prevention or treatment of
virally-induced infectious diseases. We discuss the unique roles of these agents
in modulating the cross-talk between commensal bacteria and the mucosal immune
system. In addition, we provide an overview of the unique mechanism by which
viruses are eliminated through the stimulation of type 1 interferon production by
probiotics and paraprobiotics via the activation of dendritic cells. Although
further detailed research is necessary in the future, probiotics and/or
paraprobiotics are expected to be among the rational adjunctive options for the
treatment of various viral diseases.
PMID- 29345578
TI - Searching for New Targets and Treatments in the Battle Against Squamous Cell
Carcinoma of the Head and Neck, with Specific Focus on Tumours of the Tongue.
AB - Squamous cell carcinoma of the head and neck, SCCHN, is a heterogeneous group of
tumours not only concerning the site of origin but also regarding aetiology. The
5-year survival for the whole group of SCCHN tumours has not significantly
improved over the last 20-25 years. Apart from tumour spread to lymph nodes, N
status, gains and losses of specific chromosomes are the only factors shown to be
independent prognostic markers for these tumours. Worldwide, an increasing number
of people <= 40 years are seen being affected by tongue SCC, the most common
tumour within the SCCHN group. Even without any clinical signs of metastasis, up
to 30% of all tongue SCC have histologically detectable spread to lymph nodes. In
this mini review, field cancerization, tumour microenvironment, the so called EMT
(epithelial mesenchymal transition) process and the role of viruses in
development of SCCHN are discussed as well as potential new therapeutic targets.
For the group of tongue SCC, with the increasing incidence seen in young patients
and particularly women, new data with impact on prognosis and treatment are
urgently needed. But as long as data from the analyses of several sub sites are
presented as valid for the whole group of tumours, this vital point is missed.
PMID- 29345579
TI - Genistein as a Potential Anticancer Agent Against Head and Neck Squamous Cell
Carcinoma.
AB - The use of nutraceuticals as protection drugs against chronic diseases gained a
vast success. Many studies found that nutraceuticals may reduce the tumorigenic
actions of carcinogens, inhibiting the adhesion and proliferation of tumor cells.
Genistein is a natural isoflavone preventing osteoporosis, menopause problems and
heart diseases. It is also known in China and Japan for its anticancer
properties. The available treatment protocols for Head and neck squamous cell
cancer (HNSCC) have led to poor results and new therapies are necessary. In this
paper, we will review anticancer therapeutic potential of genistein and in vitro
and in vivo studies that suggest its potential role in the treatments of HNSCC.
PMID- 29345580
TI - Multi-potent Natural Scaffolds Targeting Amyloid Cascade: In Search of
Alzheimer's Disease Therapeutics.
AB - Alzheimer's Disease (AD) once considered a rare disorder emerges as a major
health concern in recent times. The disease pathogenesis is very complex and yet
to be understood completely. However, "Amyloid Cascade" is the central event in
disease pathogenesis. Several proteins of the amyloid cascade are currently being
considered as potential targets for AD therapeutics discovery. Many potential
compounds are in clinical trials, but till now there is no known cure for the
disease. Recent years have witnessed remarkable research interest in the search
of novel concepts in drug designing for AD. Multi-targeted ligand design is a
paradigm shift in conventional drug discovery. In this process rather than
designing ligands targeting a single receptor, novel ligands have been designed/
synthesized that can simultaneously target many pathways involved in disease
pathogenesis. Here, recent developments in computational drug designing protocols
to identify multi-targeted ligand for AD have been discussed. Therapeutic
potential of different multi-potent compounds also has been discussed briefly.
Prime emphasis has been given to multi-potent ligand from natural resources.
Polyphenols are an interesting group of compounds which show efficacy against a
wide range of disease and have the property to exhibit multi-potency. Several
groups attempted to identify novel multi-potent phytochemicals for AD therapy.
Multi-potency of several polyphenols or compounds synthesized using the poly
phenolic scaffolds have been briefly discussed here. However, the multi-targeted
drug designing for AD is still in early stages, more advancement in drug
designing method/algorithm developments is urgently required to discover more
efficient compounds for AD therapeutics.
PMID- 29345583
TI - Controversies in the Cath Lab: Navigating Contemporary Conundrums Before, During
and After Intervention.
PMID- 29345581
TI - Premorbid and Illness-related Social Difficulties in Eating Disorders: An
Overview of the Literature and Treatment Developments.
AB - BACKGROUND: Social difficulties in eating disorders can manifest as predisposing
traits and premorbid difficulties, and/or as consequences of the illness.
OBJECTIVE: The aim of this paper is to briefly review the evidence of social
problems in people with eating disorders and to consider the literature on
treatments that target these features. METHOD: A narrative review of the
literature was conducted. RESULTS: People with eating disorders often manifest
traits, such as shyness, increased tendency to submissiveness and social
comparison, and problems with peer relationships before illness onset. Further
social difficulties occur as the illness develops, including impaired social
cognition and increased threat sensitivity. All relationships with family, peers
and therapists are compromised by these effects. Thus, social difficulties are
both risk and maintaining factors of eating disorders and are suitable targets
for interventions. Several forms of generic treatments (e.g. interpersonal
psychotherapy, cognitive analytic therapy, focal psychodynamic therapy) have an
interpersonal focus and show some efficacy. Guided self-management based on the
cognitive interpersonal model of the illness directed to both individuals and
support persons has been found to improve outcomes for all parties. Adjunctive
treatments that focus on specific social difficulties, such as cognitive
remediation and emotion skills training and cognitive bias modification have been
shown to have a promising role. CONCLUSION: More work is needed to establish
whether these approaches can improve on the rather disappointing outcomes that
are attained by currently used treatments for eating disorders.
PMID- 29345582
TI - Is the Impact of Starvation on the Gut Microbiota Specific or Unspecific to
Anorexia Nervosa? A Narrative Review Based on a Systematic Literature Search.
AB - BACKGROUND: The role of the gut microbiota in Anorexia Nervosa (AN) has long been
neglected by researchers, although the fact that the former is known to play an
important role in health, disease and weight regulation. Cycles of overweight and
underweight due to natural states of starvation and refeeding are normal in many
vertebrates in their ecological niches. OBJECTIVE: The aim of this review was to
compare the similarities and differences of the gut microbiota in eating
disorders with conditions of fasting and refeeding in other vertebrates. METHOD:
A systematic literature search was conducted in Pubmed and Web of Science to find
all relevant studies examining the gut microbiota in eating disorders and
different states of fasting in vertebrates for this narrative review. RESULTS:
Gut microbiota appears to differ in AN versus normal-weight individuals. Induced
fasting conditions in other vertebrates resulted in heterogeneous effects on gut
microbiota with respect to their richness, diversity and community structures.
The findings for hibernating animals were generally consistent. A decrease in
microbial richness and diversity was observed in the hibernating animal compared
to the active animal, and the community structures were linked to these
conditions. Some similarities and differences between AN and different states of
fasting in other vertebrates were found. CONCLUSION: The complexity of the
relationship between fasting and gut microbiota is difficult to interprete. A
deeper biological understanding is necessary to identify promising approaches for
the modulation of the AN gut microbiota to support established psychotherapies.
PMID- 29345584
TI - Mechanical Support in Cardiogenic Shock Complicating Acute Coronary Syndrome:
Ready for Prime Time?
AB - Cardiogenic Shock (CS) is a major challenge in current cardiology. Over the last
decade, cardiogenic shock mortality has decreased somewhat, but it still remains
high, particularly when associated with ischaemic heart disease. The challenges
are numerous and include prevention, accurate diagnosis, prompt management and
effective therapies to support a failing heart and prevent multi-organ failure.
Despite improvements in the care of Acute Coronary Syndrome (ACS), it remains the
most common cause of CS. In addition to existing medical therapy, mechanical
circulatory support has been proposed for the management of ventricular failure.
The intra-aortic balloon pump was amongst the first widely used percutaneous
mechanical support devices, and more recently, systems providing a higher level
of support have been developed. Although the evidence supporting their use is
limited, they have the potential to significantly reduce CS-associated mortality.
In this narrative review, we summarize the available evidence and discuss the
future directions regarding percutaneous mechanical circulatory support in
patients with left ventricular dysfunction and CS complicating ACS.
PMID- 29345585
TI - Mandatory Reporting of Coronary Artery Calcifications Incidentally Noted on Chest
Multi-Detector Computed Tomography: A Multicentre Experience.
AB - BACKGROUND: Coronary Artery Calcifications (CACs) are associated with coronary
atherosclerosis and Cardiovascular (CV) events. In "non-cardiovascular" settings,
CACs can be easily detected on chest Multi-Detector Computed Tomography (MDCT).
Their evaluation may help to better stratify CV risk in the general population,
especially for primary prevention. AIMS: We retrospectively evaluated the
relationship between CAC distribution and CV risk, determined by Framingham Risk
Score (FRS), in a cohort of patients who underwent chest MDCT performed for
several clinical indications. METHOD: We retrospectively recruited 305 patients
(194 men, 111 women; mean age 70.5 years) from 3 different Italian centres.
Patients with coronary stent, pacemaker and/or CV devices were excluded from the
study. Circumflex Artery (LCX), Left Main Coronary Artery (LMCA), left Anterior
Descending artery (LAD) and right coronary artery (RCA) were analysed. RESULTS:
From a total population of 305 patients, 119 (39%) had low FRS (<10%), 115 (38%)
had intermediate FRS (10-20%), and 71 (23%) had high FRS (>20%). The study
identified 842 CACs located in decreasing order as follows: RCA (34.5%), LAD
(32.3%), LCX (28%) and LMCA (13%). Statistical two-step analysis subdivided
patients into two clusters according to FRS (risk threshold = 12.38%): cluster I
(mean 9.34) and cluster II (mean 15.09). A significant association between CAC
distribution and cluster II was demonstrated. CACs were mostly detected in
patients with intermediate FRS. All patients (100%) with the highest CV risk
showed intermediate RCA and LMCA involvement. CONCLUSION: Radiologists can note
the distribution of CACs on a chest MDCT and should mandatorily record them in
their reports. Depending on CAC presence and location, these findings may have
important clinical implications, mostly in asymptomatic patients with
intermediate FRS. This information may reclassify a patients' CV risk and improve
clinical management.
PMID- 29345586
TI - What is the Role of Cangrelor in Patients Undergoing PCI?
AB - Dual antiplatelet therapy with aspirin and oral P2Y12-receptor inhibitors
prevents ischemic events in patients undergoing Percutaneous Coronary
Intervention (PCI). However, oral administration of antiplatelet drugs cause
delay of onset of platelet inhibition in P2Y12-inhibitor naive patients.
Cangrelor is a novel P2Y12-receptor inhibitor which is administrated
intravenously and thus allows immediate antiplatelet inhibition during PCI. Due
to its unique pharmacokinetics with fast onset of platelet inhibition and very
short plasma half-life it allows effective and controllable periprocedural
platelet inhibition. It could reduce short-term ischemic events in large
randomized clinical trials. The present article reviews the available evidence
and application on cangrelor use in clinical practice.
PMID- 29345587
TI - Is there a Role for Oral Triple Therapy in Patients with Acute Coronary Syndromes
Without Atrial Fibrillation?
AB - BACKGROUND: Acute Coronary Syndrome (ACS) patients, despite treatment with Dual
Anti- Platelet Therapy (DAPT), have up to 10% risk of recurrent Major Adverse
Cardiac Events (MACE) in the short term. METHODS: Here we review studies using
more potent antithrombotic agent combinations to reduce this risk, namely Triple
Therapy (TT) with the addition of an oral anticoagulant, PAR-1 antagonist, or
cilostazol to DAPT (mainly aspirin and clopidogrel), and discuss the limitations
of trials to date. RESULTS: Generally speaking, TT leads to an increase in
bleeding. Vorapaxar showed a signal for reducing ischaemic events, but increased
intracranial haemorrhage 3-fold in the subacute phase of ACS, although remains an
option for secondary prevention beyond the immediate subacute phase, particularly
if prasugrel or ticagrelor are not available. Non-Vitamin K Oral Anticoagulants
(NOACs) all increased bleeding, with only modest reduction in MACE noted with low
dose rivaroxaban. Rivaroxaban can be considered combined with aspirin and
clopidogrel in ACS patients at high ischaemic and low bleeding risk, without
prior stroke/TIA. The combination of P2Y12 inhibitor and NOAC, without aspirin,
looks promising. DAPT may be replaced, not by TT, but by dual therapy comprising
a NOAC with a P2Y12 inhibitor. CONCLUSION: More potent antithrombotic regimens
increase bleeding and should only be considered on an individual basis, after
careful risk stratification. Accurate risk stratification of ACS patients, for
both ischaemic and bleeding risk, is essential to allow individualised treatment.
PMID- 29345588
TI - The Role of Percutaneous Coronary Intervention in the Treatment of Chronic Total
Occlusions: Rationale and Review of the Literature.
AB - BACKGROUND: Chronic total occlusion (CTO) of a coronary artery is defined as an
occluded segment with no antegrade flow and a known or estimated duration of at
least 12 weeks. OBJECTIVE: We considered the current literature describing the
indications and clinical outcomes for de-novo CTO- percutaneous coronary
intervention (PCI), and discuss the role of CTO-PCI and future directions for
this procedure. METHOD: Databases (PubMed, the Cochrane Library, Embase, EBSCO,
Web of Science, and CINAHL were searched and relevant studies of CTO-PCI were
selected for review. RESULTS: The prevalence of coronary artery CTO's has been
reported to be ~ 20% among patients undergoing diagnostic coronary angiography
for suspected coronary artery disease. Revascularization of any CTO can be
technically challenging and a time-consuming procedure with relatively low
success rates and may be associated with a higher incidence of complications,
particularly at non-specialized centers. However, with an increase in experience
and technological advances, several centers are now reporting success rates above
80% for these lesions. There is marked variability among studies in reporting
outcomes for CTO-PCI with some reporting potential mortality benefit, better
quality of life and improved cardiac function parameters. Anecdotally, properly
selected patients who undergo a successful CTO-PCI most often have profound
relief of ischemic symptoms. Intuitively, it makes sense to revascularize an
occluded coronary artery with the goal of improving cardiovascular function and
patient quality of life. CONCLUSIONS: CTO-PCI is a rapidly expanding specialized
procedure in interventional cardiology and is reasonable or indicated if the
occluded vessel is responsible for symptoms or in selected patients with silent
ischemia in whom there is a large amount of myocardium at risk and PCI is likely
to be successful.
PMID- 29345589
TI - Neonatal Systemic Thrombosis: An Updated Overview.
AB - Thromboembolic disease is a complex disorder with a multifactorial aetiology and
a severe outcome. In newborns and children it may be missed or diagnosed late,
thus worsening the prognosis. The neonatal disease is different from the disorder
affecting older children and adults. However, scant epidemiological data and few
randomised clinical trials regarding paediatric patients are available, and
treatment recommendations are largely based on adult guidelines. Younger patients
then have several decades over which they will suffer from the complications of
thrombosis and risk of a new thrombotic episode. Current knowledge about neonatal
thromboembolic disease and its prevention is reviewed here along with maternal,
foetal, neonatal, pharmacological, environmental, lifestyle and occupational
contributing factors. Additional data are urgently needed to improve diagnostic
and therapeutic strategies and patient outcomes.
PMID- 29345590
TI - What is the Role for Glycoprotein IIb/IIIa Inhibitor Use in the Catheterization
Laboratory in the Current Era?
AB - BACKGROUND: In the era of dual antiplatelet therapy of aspirin and clopidogrel
and systematic stent implantation, Glycoprotein IIb/IIIa Inhibitors (GPI),
including abciximab, eptifibatide and tirofiban, proved beneficial in improving
early outcome of Percutaneous Coronary Intervention (PCI), especially in higher
risk clinical and/or anatomical subsets. This was associated however, with an
increased incidence of bleeding complications. OBJECTIVE: To review whether the
established results of GPI in PCI are maintained in the contemporary era of more
effective antiplatelet agents (i.e., prasugrel, ticagrelor and cangrelor) and
safer anticoagulants (i.e., bivalirudin) and interventional techniques (i.e.,
radial approach). METHODS: The most relevant evidence on the use of GPI in stable
coronary artery disease, non-STelevation coronary syndromes and ST-elevation
myocardial infarction was reviewed. RESULTS: Overall the relative efficacy and
safety of GPI in contemporary PCI is maintained, largely irrespective of the use
of more effective antiplatelet agents and/or safer anticoagulants and
interventional techniques. However, an increase in the absolute occurrence of
major and/or minor bleeding and/or need for blood transfusions is generally
observed. CONCLUSION: Because of the persistent benefit of GPI in limiting early
ischemic complications, especially in higher risk clinical and/or anatomical
subsets, and the associated risk of increased bleeding complications, also in
contemporary PCI, these agents should currently be used on a selective rather
than routine basis, including bail out administration for peri-procedural
thrombotic complications.
PMID- 29345591
TI - Should Antithrombotic Treatment Strategies in East Asians Differ from Caucasians?
AB - With over 1.5 billion people, East Asians are the most populous race in the
world. Health status in this population is an important global issue. In the
contemporary trials of antithrombotic treatment, East Asian patients have a lower
risk for atherothrombotic diseases (especially, Coronary Artery Disease [CAD])
and a higher risk for bleeding (especially, gastrointestinal bleeding and
hemorrhagic stroke). Despite these observations, antithrombotic treatment
strategies in East Asian patients are mainly based on the American or European
guidelines that are derived from randomized, controlled trials including mostly
Caucasians. Despite a low response to clopidogrel, East Asian patients with CAD
show a similar or even a lower rate of ischemic event occurrence and higher
bleeding risk compared with Caucasian patients. The latter is referred to as the
"East Asian Paradox", suggesting a dissimilar therapeutic window for antiplatelet
therapy than Caucasians. In addition, different net clinical benefits have been
observed between the races with potent P2Y12 inhibitors that may be related to
racial differences in pharmacokinetic and pharmacodynamic profiles. Furthermore,
there is emerging concern regarding differences between East Asian vs. Western
patients in pharmacodynamic and clinical efficacies of anticoagulant agents. We
now summarize experimental and clinical evidence of the efficacy and safety of
antithrombotic agents in the East Asian population. We suggest the concept of
"race-tailored antithrombotic treatment" in CAD patients and/or in patients
undergoing percutaneous coronary intervention.
PMID- 29345592
TI - Prolonging Ticagrelor Beyond a Year of Acute Coronary Syndrome: Worth or Harmful?
AB - Platelet activation plays a central role in triggering and complicating acute
coronary syndromes, especially in case of stent thrombosis and myocardial
infarction. On top of aspirin, P2Y12- inhibitors are successfully used to treat
and prevent these events for a duration of one year after an acute coronary
episode or 6 months after drug-eluting stent implantation. However, patients with
acute coronary syndromes remain at heightened risk for recurrent ischemic events
after the recommended durations of P2Y12-inhibitors and therefore, prolonging
treatment is often considered in clinical practice. However, the higher risk for
bleeding limits the utility of such approach to a restricted group who is still
poorly defined by available measures. This review aims to discuss potential
benefits and highlight important pitfalls of prolonged treatment with P2Y12
inhibitors, with a focus on ticagrelor, an attractive reversible P2Y12-inhibitor
in patients after myocardial infarction.
PMID- 29345593
TI - Antithrombotic Therapy After TAVR.
AB - Transvascular Aortic Valve Replacement (TAVR) has emerged as a treatment option
in patients with severe aortic stenosis who are inoperable and has recently been
evaluated in patients with intermediate surgical risk. The number of procedures
is increasing worldwide in parallel with the demographic changes in industrial
countries. The risk for cerebral embolism is of main concern and represents a
major determinant for prognosis and quality of live after TAVR. The empiric
antithrombotic therapy consists of Dual Antiplatelet Therapy (DAPT); However the
risk-benefit of this approach is lacking evidence from randomized, placebo
controlled trials regarding choice and duration of antithrombotic treatment.
Although anticoagulation is generally not recommended in patients with aortic
bioprosthesis without atrial fibrillation, there is current uncertainty whether
combination of antiplatelet and anticoagulant therapy or anticoagulation alone
might represent a more favorable antithrombotic regimen compared to the current
empiric standard of DAPT. In addition, so far undetected atrial fibrillation is
highly prevalent in the elderly population undergoing TAVR. In particular, the
favorable safety profile of Non-Vitamin K Oral Anticoagulants (NOAC) offers an
attractive option. A number of trials are currently underway to investigate the
benefit of NOAC in patients with and without atrial fibrillation undergoing TAVR.
The present article reviews the available evidence concerning stroke risk in TAVR
patients and the current and future role of antithrombotic therapy during and
after the procedure.
PMID- 29345594
TI - Should STEMI Patients Receive Opiate Analgesia? The Morphine Paradox.
AB - BACKGROUND: The very significant benefit of P2Y12 receptor inhibitor
administration in patients with ST-elevation myocardial infarction (STEMI), in
reducing future ischaemic events and stent thrombosis, is undisputed. Morphine
analgesia is very frequently co-administered to these patients for pain relief,
along with antiplatelet therapy, at the time of presentation, and prior to
reperfusion with primary percutaneous coronary intervention. METHODS: Research
and online content related to opiates use in STEMI was reviewed. Bibliographies
of retrieved studies were searched manually for additional studies and reviews.
RESULTS: There is sufficient data from pharmacokinetic and pharmacodynamic
studies showing that the co-administration of morphine with oral P2Y12 receptor
inhibitor results in delayed antiplatelet effects. However, whether this results
in adverse outcomes remains unclear. Data from studies reporting the effect of
morphine on clinical outcomes in STEMI are inconsistent, although they tend to be
underpowered to show an effect on hard clinical outcomes, but some clearly show a
relationship between morphine use and infarct size. Strategies to overcome the
potentially significant negative impact of morphine on platelet reactivity in
STEMI are discussed. CONCLUSION: Whilst clearly definitive, adequately powered,
randomised controlled trials are lacking, we would recommend avoiding the
combination of morphine with oral P2Y12 receptor inhibitors and recommend
alternative strategies including intravenous platelet inhibitor strategies, in
high risk patients.
PMID- 29345595
TI - Hospital Management of Severe Hypertriglyceridemia in Children.
AB - BACKGROUND: Severe Hypertriglyceridemia (HTG), i.e., plasma triglyceride levels
exceeding 1000 mg/dL, is one of the established causes of acute pancreatitis and
severe abdominal pain. There are no established pediatric guidelines regarding
treatment of children and adolescents with severe HTG. OBJECTIVE: To review the
pathophysiology and etiology of severe HTG in the pediatric age group, and to
discuss management options. METHOD AND RESULTS: Severe HTG is usually due to
deficient or absent Lipoprotein Lipase (LPL) activity, which can be due to
primary genetic etiology or secondary causes triggering HTG in those with
underlying genetic susceptibility. Hospitalization is indicated for patients with
severe HTG who are symptomatic with abdominal pain or pancreatitis, in those with
uncontrolled diabetes requiring insulin, or, in those with substantial elevations
of plasma TG. Fasting followed by fat free diet until plasma TG declines to
<1000mg/dL is essential. Subsequently, stringent fat restriction followed by
slowly increasing the dietary fat while maintaining the plasma TG concentration
at a targeted level is recommended. Insulin infusions are helpful in patients who
have some LPL activity, especially in those with diabetes. Plasmapheresis may be
considered in those with severe pancreatitis, shock or multi-organ failure.
Medications such as fibrates and omega-3 fatty acids are not effective if LPL
activity is absent or when plasma TG is >1800 mg/dL. Medications only have an
adjunct role in the management. Low fat diet, lifestyle changes, weight loss,
control of secondary causes, and patient education form the mainstay of
management once the patient is discharged.
PMID- 29345596
TI - The Coronary Artery Risk Detection in Appalachian Communities (CARDIAC) Project:
An 18 Year Review.
AB - BACKGROUND: The Coronary Artery Risk Detection in Appalachian Communities
(CARDIAC) Project is a chronic disease risk factor surveillance, intervention,
and research initiative aimed at combating the unacceptably high prevalence of
heart disease, diabetes, and other chronic illnesses in West Virginia. OBJECTIVES
AND METHODS: The school-based public health project identifies health risk
factors in children, educates families, informs primary care physicians, and
provides resources to schools to help improve population health, beginning with
children. RESULTS AND CONCLUSION: Details regarding methodology, results, and
conclusions derived from this unique public health initiative that has screened
over 200,000 children are the subject of this 18- year review.
PMID- 29345597
TI - Pediatric Markers of Adult Cardiovascular Disease.
AB - BACKGROUND: Cardiovascular diseases are the leading cause of death worldwide.
While cardiovascular disease typically does not occur until adulthood, the
pathogenesis of atherosclerotic cardiovascular disease starts in early childhood.
OBJECTIVE: The purpose of this review is to describe the evidence that the
process of atherosclerosis begins in childhood, as well as identify the risk
factors present in childhood that are associated with the presence of
atherosclerotic cardiovascular disease in childhood as well as future
cardiovascular events in adulthood. RESULTS AND CONCLUSION: There is much
accumulating evidence linking modifiable risk factors that are already present in
childhood and that strongly predict future cardiovascular disease. The selective
targeting of modifiable risk factors in childhood, including body mass index,
holds promise in reducing the burden of adult cardiovascular disease. Future
research studies should focus on elucidating the mechanisms which drive the
pathogenesis of atherosclerosis in childhood and young adulthood, as well as
identifying which interventions are most effective at limiting the progression of
atherosclerosis and thus reducing future cardiovascular disease.
PMID- 29345598
TI - Dolutegravir-Related Neurological Adverse Events: A Case Report of Successful
Management with Therapeutic Drug Monitoring.
AB - OBJECTIVE: Dolutegravir (DTG), a highly effective second-generation HIV integrase
inhibitor with high genetic barrier to resistance, has shown excellent
tolerability and safety profiles in clinical trials. However, some patients may
experience neurological or psychiatric adverse effects leading to DTG
discontinuation. CASE REPORT: This report describes a case of 29-year-old woman
who developed neurological adverse events after starting the DTG-based
antiretroviral therapy. Serum DTG concentrations were supratherapeutic which has
required a dosing interval adjustment. The findings of this case report suggest
that Therapeutic Drug Monitoring might be useful in individuals expressing
unusual DTG pharmacokinetics.
PMID- 29345599
TI - Crystalline Ethylene Oxide and Propylene Oxide Triblock Copolymer Solid
Dispersion Enhance Solubility, Stability and Promoting Time- Controllable Release
of Curcumin.
AB - AIMS AND BACKGROUND: The design and development of an effective medicine are,
however, often faced with a number of challenges. One of them is the close
relationship of drug's bioavailability with solubility, dissolution rate and
permeability. The use of curcumin's (CUR) therapeutic potential is limited by its
poor water solubility and low chemical stability. The purpose was to evaluate the
effect of polymer and solid dispersion (SD) preparation techniques to enhance the
aqueous solubility, dissolution rate and stability of the CUR. The recent patents
on curcumin SD were reported as (i) curcumin with polyvinylpyrrolidone (CN20071
32500 20071214, WO2006022012 and CN20151414227 20150715), (ii) curcumin
zinc/polyvinylpyrrolidone (CN20151414227 20150715), (iii) curcumin-poloxamer 188
(CN2008171177 20080605), (iv) curcumin SD prepared by melting method
(CN20161626746-20160801). MATERIALS AND METHODS: SD obtained by co-preciptation
or microwave fusion and the physical mixture of CUR with Poloxamer-407 (P-407),
Hydroxypropylmetylcellulose-K4M (HPMC K4M) and Polyvinylpyrrolidone-K30 (PVP-K30)
were prepared at the ratios of 1:2; 1:1 and 2:1. The samples were evaluated by
solubility, stability, dissolution rate and characterized by SEM, PXRD, DSC and
FTIR. RESULTS: The solubility, stability (pH 7.0) and dissolution rate were
significantly greater for SD (CUR:P-407 1:2). The PXRD,SEM and DSC indicated a
change in the crystalline state of CUR. The enhancement of solubility was
dependent on a combination of factors including the weight ratio, preparation
techniques and carrier properties. The drug release data fitted well with the
Weibull equation, indicating that the drug release was controlled by diffusion,
polymer relaxation and erosion occurring simultaneously. CONCLUSION: Thus, these
SDs, specifically CUR:P-407 1:2 w/w, can overcome the barriers of poor
bioavailability to reap many beneficial properties.
PMID- 29345600
TI - An Open-Source Storage Solution for Cryo-Electron Microscopy Samples.
AB - Cryo-electron microscopy (cryo-EM) enables the study of biological structures in
situ in great detail and to solve protein structures at Angstrom level
resolution. Due to recent advances in instrumentation and data processing, the
field of cryo-EM is a rapidly growing. Access to facilities and national centers
that house the state-of-the-art microscopes is limited due to the ever-rising
demand, resulting in long wait times between sample preparation and data
acquisition. To improve sample storage, we have developed a cryo-storage system
with an efficient, high storage capacity that enables sample storage in a highly
organized manner. This system is simple to use, cost-effective and easily
adaptable for any type of grid storage box and dewar and any size cryo-EM
laboratory.
PMID- 29345601
TI - Vaccine effectiveness and use of collar impregnated with insecticide for reducing
incidence of Leishmania infection in dogs in an endemic region for visceral
leishmaniasis, in Brazil.
AB - Although a national programme for control of visceral leishmaniosis (VL) is being
run in Brazil, the disease continues to spread. This programme is essentially
based on culling infected dogs from endemic regions. Thus, there is an urgent
need to develop other control measures against VL to deter its advance. Here, a
subunit vaccine, a recombinant vaccine, an insecticide-impregnated collar and the
associations between these measures were evaluated for reducing the incidence of
Leishmania infection in dogs. This was through a cohort study conducted in an
endemic region of Brazil, considering the incidence and time of total exposure
over a period of 1 year. The incidence of VL was estimated by means of
serological and molecular diagnostic tests, 180 and 360 days after the
application of the control measures. The estimates of the effectiveness (EF) were
not significant in any cohort. The EF of the subunit vaccine, the recombinant
vaccine and the collar were 26.4%, 32.8% and 57.7% and the upper limit of the 95%
confidence interval for EF were 63.7%, 67.9% and 82.5%, respectively. In
conclusion, under the conditions of this study, none of the immunogens for VL
control was sufficiently effective to protect dogs against infection. On the
other hand, use of collars impregnated with insecticide seems to constitute a
method with better prognosis, corroborating other studies in this field.
PMID- 29345602
TI - The mental health of adolescents and pre-adolescents living with inherited
arrhythmia syndromes: a systematic review of the literature.
AB - Potentially fatal arrhythmias add to the mental health challenges of adolescence.
This systematic review sought to summarise current knowledge regarding the mental
health of adolescents and pre-adolescents diagnosed with inherited arrhythmia
syndromes. Searches combining psychological problems with inherited cardiac
arrhythmia diagnoses identified 16 studies with paediatric (<18 years) inherited
arrhythmia patients. All studies were cross-sectional; 8/16 required an
implantable cardioverter defibrillator. Methods were quantitative (n=11),
qualitative (n=4), or mixed (n=1), with 14-100% of participants having an
inherited arrhythmia syndrome. Mean/median age in 13/16 studies was 12-16 years.
Patients and parents reported lower quality of life, particularly in relation to
physical function, social relationships, restriction of peer activities, bodily
pain, and mental and emotional health. Self-perceptions and behaviour were
similar to healthy populations. Rates of anxiety and depression (15-33% of these
patients) were not increased in these studies where patients were assessed 2+
years after diagnosis. Higher mental health risk occurred among patients who have
a diagnosed sibling, those with cardiomyopathy, and those who report decreased
quality of life. Mental health research among youth with inherited arrhythmias is
extremely limited and of low quality. Data, primarily from patients 2-4 years
after diagnosis or treatment with an implantable cardioverter defibrillator,
indicate that quality of life may be decreased and 15-33% experience mental
health issues. Future research is required to examine the mental health and
quality of life of paediatric patients with inherited arrhythmia syndromes,
whether or not they have an implantable cardioverter defibrillator, from time of
diagnosis.
PMID- 29345603
TI - Association between household food security and infant feeding practices in urban
informal settlements in Nairobi, Kenya.
AB - Studies in urban informal settlements show widespread inappropriate infant and
young child feeding (IYCF) practices and high rates of food insecurity. This
study assessed the association between household food security and IYCF practices
in two urban informal settlements in Nairobi, Kenya. The study adopted a
longitudinal design that involved a census sample of 1110 children less than 12
months of age and their mothers aged between 12 and 49 years. A questionnaire was
used to collect information on: IYCF practices and household food security.
Logistic regression was used to determine the association between food insecurity
and IYFC practices. The findings showed high household food insecurity; only
19.5% of the households were food secure based on Household Insecurity Access
Score. Infant feeding practices were inappropriate: 76% attained minimum meal
frequency; 41% of the children attained a minimum dietary diversity; and 27%
attained minimum acceptable diet. With the exception of the minimum meal
frequency, infants living in food secure households were significantly more
likely to achieve appropriate infant feeding practices than those in food
insecure households: minimum meal frequency (adjusted odds ratio (AOR)=1.26,
P=0.530); minimum dietary diversity (AOR=1.84, P=0.046) and minimum acceptable
diet (AOR=2.35, P=0.008). The study adds to the existing body of knowledge by
demonstrating an association between household food security and infant feeding
practices in low-income settings. The findings imply that interventions aimed at
improving infant feeding practices and ultimately nutritional status need to also
focus on improving household food security.
PMID- 29345604
TI - A new approach of three-dimensional guidance in paediatric cath lab: segmented
and tessellated heart models for cardiovascular interventions in CHD.
AB - BACKGROUND: Optimal imaging is essential for catheter-based interventions in CHD.
The three-dimensional models in volume-rendering technique currently in use are
not standardised. This paper investigates the feasibility and impact of novel
three-dimensional guidance with segmented and tessellated three-dimensional heart
models in catheterisation of CHD. In addition, a nearly radiation-free two- to
three-dimensional registration and a biplane overlay were used.Methods and
resultsWe analysed 60 consecutive cases in which segmented tessellated three
dimensional heart models were merged with live fluoroscopy images and aligned
using the tracheal bifurcation as a fiducial mark. The models were generated from
previous MRI or CT by dedicated medical software. We chose the stereo-lithography
format, as this promises advantage over volume-rendering-technique models
regarding visualisation. Prospects, potential benefits, and accuracy of the two-
to three-dimensional registration were rated separately by two paediatric
interventionalists on a five-point Likert scale. Fluoroscopy time, radiation
dose, and contrast dye consumption were evaluated. Over a 10-month study period,
two- to three-dimensional image fusion was applied to 60 out of 354 cases. Of the
60 catheterisations, 73.3% were performed in the context of interventions. The
accuracy of two- to three-dimensional registration was sufficient in all cases.
Three-dimensional guidance was rated superior to conventional biplane imaging in
all 60 cases. We registered significantly smaller amounts of used contrast dye
(p<0.01), lower levels of radiation dose (p<0.02), and less fluoroscopy time
(p<0.01) during interventions concerning the aortic arch compared with a control
group. CONCLUSIONS: Two- to three-dimensional image fusion can be applied
successfully in most catheter-based interventions of CHD. Meshes in stereo
lithography format are accurate and base for standardised and reproducible three
dimensional models.
PMID- 29345605
TI - Histopathological evaluation of aortic coarctation after conventional balloon
angioplasty in neonates.
AB - BACKGROUND: Optimal management strategy for native aortic coarctation in neonates
and young infants is still a matter of debate. The surgical procedure,
histopathologic research, and clinical outcome in 15 neonates who underwent
surgery after successful balloon angioplasty is the basis of this study. METHOD:
Between 01 October, 2014 and 01 August, 2017, we enrolled 15 patients with native
aortic coarctation for this study. These patients had complications regarding
recoarctation, following balloon angioplasty intervention at our institute and
other centres. Surgically extracted parts were examined histopathologically and
patient's data were collected retrospectively.ResultThe reasons for recurrence of
recoarctation after balloon angioplasty are as follows: patients with higher
preoperative echocardiographic gradients had recoarctation earlier, neointimal
proliferation, aortic intimal fibrosis at the region of ductal insertion, and
ductal residual tissue debris after balloon angioplasty. No repeat intervention
was required in the 15 patients who underwent surgery followed by balloon
angioplasty. Early mortality was seen in one patient after surgery. Postoperative
complication in the surgical group occurred in the form of chylothorax in one
patient. CONCLUSION: In centres in which the neonatal ICU is inexperienced,
balloon angioplasty is particularly recommended. In developing neonatal clinics,
balloon angioplasty, when performed on patients at their earliest possible age,
delays actual corrective operation to a later date, which in turn provides less
risky surgical outcomes in infants who are gaining weight, growing, and do not
have any haemodynamic complaints.
PMID- 29345606
TI - Prevalence of transmitted drug resistance among HIV-1 treatment-naive patients in
Beijing.
AB - To optimise patients' outcomes and gain insight into transmitted drug resistance
(TDR) among human immunodeficiency virus (HIV)-1 treatment-naive patients in
Beijing, the prevalence of TDR was assessed. Demographic and clinical data of
1241 treatment-naive patients diagnosed between April 2014 and February 2015 were
collected. TDR was defined using the Stanford University HIV drug resistance
mutations database. The risk factors were evaluated by multi-logistic regression
analysis. Among 932 successfully amplified cases, most were male (96.78%) and
infected through men having sex with men (91.74%). Genotype were CRF01_AE
(56.44%), B (20.60%), CRF07_BC (19.96%), C (1.61%) and other genotypes (1.39%).
The overall prevalence of TDR was 6.12%. Most frequent mutations occurred in non
nucleoside reverse transcriptase inhibitors (NNRTIs) (3.11%), followed by
protease inhibitors (PIs) (2.25%) and nucleoside reverse transcriptase inhibitors
(NRTIs) (1.32%). Furthermore, HIV-1 genotype was associated with high risk of
resistance, in which genotype C and other genotype may have higher risk for
resistance. The prevalence among treatment-naive patients in Beijing was low.
Resistance to NNRTIs was higher than with PIs or NRTIs. Continuous monitoring of
regional levels of HIV-1 TDRs would contribute to improve treatment outcomes and
prevent failures.
PMID- 29345607
TI - The Impact of Isolation Precautions on Hand Hygiene Frequency by Healthcare
Workers.
PMID- 29345608
TI - Food choices to meet nutrient recommendations for the adult Brazilian population
based on the linear programming approach.
AB - OBJECTIVE: To identify optimal food choices that meet nutritional recommendations
to reduce prevalence of inadequate nutrient intakes. DESIGN: Linear programming
was used to obtain an optimized diet with sixty-eight foods with the least
difference from the observed population mean dietary intake while meeting a set
of nutritional goals that included reduction in the prevalence of inadequate
nutrient intakes to <=20 %. SETTING: Brazil. SUBJECTS: Participants (men and
women, n 25 324) aged 20 years or more from the first National Dietary Survey
(NDS) 2008-2009. RESULTS: Feasible solution to the model was not found when all
constraints were imposed; infeasible nutrients were Ca, vitamins D and E, Mg, Zn,
fibre, linolenic acid, monounsaturated fat and Na. Feasible solution was obtained
after relaxing the nutritional constraints for these limiting nutrients by
including a deviation variable in the model. Estimated prevalence of nutrient
inadequacy was reduced by 60-70 % for most nutrients, and mean saturated and
trans-fat decreased in the optimized diet meeting the model constraints.
Optimized diet was characterized by increases especially in fruits (+92 g), beans
(+64 g), vegetables (+43 g), milk (+12 g), fish and seafood (+15 g) and whole
cereals (+14 g), and reductions of sugar-sweetened beverages (-90 g), rice (-63
g), snacks (-14 g), red meat (-13 g) and processed meat (-9.7 g). CONCLUSION:
Linear programming is a unique tool to identify which changes in the current diet
can increase nutrient intake and place the population at lower risk of nutrient
inadequacy. Reaching nutritional adequacy for all nutrients would require major
dietary changes in the Brazilian diet.
PMID- 29345609
TI - Dietary patterns and their association with adiponectin and leptin concentrations
throughout pregnancy: a prospective cohort.
AB - The aim of this study was to evaluate the association of dietary patterns (DP)
with maternal adiposity indicators, leptin, adiponectin and insulin
concentrations during pregnancy. A prospective cohort of pregnant women followed
up at the 5th-13th, 20th -26th and 30th-36th gestational weeks and 30-40 d
postpartum was conducted in Rio de Janeiro. A FFQ was administered in the third
trimester (30th-36th gestational weeks). The reduced rank regression procedure
was used to identify DP that explain response variables (dietary fibre and total
fat) related to indicators of maternal adiposity (postpartum weight retention and
gestational weight gain (GWG) adequacy), and plasma leptin, adiponectin and
insulin concentrations. The associations between tertiles of DP and the outcomes
were determined using logistic regression or longitudinal linear mixed-effect
regression models. The mean daily energy intake during pregnancy was 10 104 (sd
3234) kJ (2415 (sd 773) kcal), and GWG was 11.9 (sd 4.2) kg. In all, 40 % of
women presented pre-gestational overweight/obesity. Excessive GWG occurred in
34.7 % of pregnant women and 56.6 % were overweight/obese at postpartum. The
'common-Brazilian' DP (characterised by higher intake of beans, rice and lower
intake of fast food/snacks, candies/table sugar and processed meats/bacon) was
positively associated with adiponectin (beta=1.07; 95 % CI 0.17, 1.98). The
'Western' DP (characterised by higher intake of fast food/snacks and processed
meat/bacon and lower intake of noodles/pasta/roots/tubers and sodas) was
negatively associated with adiponectin (beta=-1.11; 95 % CI -2.00, -0.22) and
positively associated with leptin concentrations (beta=64.9; 95 % CI 22.8, 107.0)
throughout pregnancy. It may be suggested that the 'common-Brazilian' is a
healthy DP and beneficial for serum concentrations of adiponectin and leptin.
PMID- 29345610
TI - Adherence to Central-Line Insertion Practices (CLIP) with Peripherally Inserted
Central Catheters (PICC) and Central Venous Catheters (CVC): A Prospective Study
of 50 Hospitals in China.
PMID- 29345611
TI - Accuracy of Provider-Selected Indications for Antibiotic Orders.
AB - Documentation of antibiotic indication provides helpful information for
antimicrobial stewardship, but accuracy is not understood. Review of 396
antibiotic orders in a pediatric ICU and adult medicine step-down unit found 90%
agreement between provider-selected indication and independent review. Prompts to
enter antibiotic indication during order entry provide largely accurate
information. Infect Control Hosp Epidemiol 2018;39:111-113.
PMID- 29345612
TI - Fit Characteristics of N95 Filtering Facepiece Respirators and the Accuracy of
the User Seal Check among Koreans.
AB - Adequate facepiece fit of N95 filtering facepiece respirators (FFRs) is crucial
for optimal protection against airborne pathogens. The quantitative fit test
(QNFT) pass rates of the 4 N95 FFR models commonly used in Korea were below 50%.
Male sex was identified as a single independent predictive factor for QNFT pass.
Infect Control Hosp Epidemiol 2018;39:104-107.
PMID- 29345613
TI - Comparative transcriptomics of Aspergillus fumigatus strains upon exposure to
human airway epithelial cells.
AB - Aspergillus fumigatus is an opportunistic, ubiquitous, saprophytic mould that can
cause severe allergic responses in atopic individuals as well as life-threatening
infections in immunocompromised patients. A critical step in the establishment of
infection is the invasion of airway epithelial cells by the inhaled fungi.
Understanding how A. fumigatus senses and responds to airway cells is important
to understand the pathogenesis of invasive pulmonary aspergillosis. Here, we
analysed the transcriptomes of two commonly used clinical isolates, Af293 and
CEA10, during infection of the A549 type II pneumocyte cell line in vitro. We
focused our RNA-seq analysis on the core set of genes that are present in the
genomes of the two strains. Our results suggest that: (a) A. fumigatus does not
mount a conserved transcriptional response to airway epithelial cells in our in
vitro model and (b) strain background and time spent in the tissue culture media
have a greater impact on the transcriptome than the presence of host cells. Our
analyses reveal both common and strain-specific transcriptional programmes that
allow for the generation of hypotheses about gene function as it pertains to
pathogenesis and the significant phenotypic heterogeneity that is observed among
A. fumigatus isolates.
PMID- 29345615
TI - Variability in neural networks.
AB - Experiments on neurons in the heart system of the leech reveal why rhythmic
behaviors differ between individuals.
PMID- 29345614
TI - Output variability across animals and levels in a motor system.
AB - Rhythmic behaviors vary across individuals. We investigated the sources of this
output variability across a motor system, from the central pattern generator
(CPG) to the motor plant. In the bilaterally symmetric leech heartbeat system,
the CPG orchestrates two coordinations in the bilateral hearts with different
intersegmental phase relations (Deltaphi) and periodic side-to-side switches.
Population variability is large. We show that the system is precise within a
coordination, that differences in repetitions of a coordination contribute little
to population output variability, but that differences between bilaterally
homologous cells may contribute to some of this variability. Nevertheless, much
output variability is likely associated with genetic and life history differences
among individuals. Variability of Deltaphi were coordination-specific: similar at
all levels in one, but significantly lower for the motor pattern than the CPG
pattern in the other. Mechanisms that transform CPG output to motor neurons may
limit output variability in the motor pattern.
PMID- 29345616
TI - Inhibition of oxidative stress in cholinergic projection neurons fully rescues
aging-associated olfactory circuit degeneration in Drosophila.
AB - Loss of the sense of smell is among the first signs of natural aging and
neurodegenerative diseases such as Alzheimer's and Parkinson's. Cellular and
molecular mechanisms promoting this smell loss are not understood. Here, we show
that Drosophila melanogaster also loses olfaction before vision with age. Within
the olfactory circuit, cholinergic projection neurons show a reduced odor
response accompanied by a defect in axonal integrity and reduction in synaptic
marker proteins. Using behavioral functional screening, we pinpoint that
expression of the mitochondrial reactive oxygen scavenger SOD2 in cholinergic
projection neurons is necessary and sufficient to prevent smell degeneration in
aging flies. Together, our data suggest that oxidative stress induced axonal
degeneration in a single class of neurons drives the functional decline of an
entire neural network and the behavior it controls. Given the important role of
the cholinergic system in neurodegeneration, the fly olfactory system could be a
useful model for the identification of drug targets.
PMID- 29345617
TI - Loss of functional BAP1 augments sensitivity to TRAIL in cancer cells.
AB - Malignant mesothelioma (MM) is poorly responsive to systemic cytotoxic
chemotherapy and invariably fatal. Here we describe a screen of 94 drugs in 15
exome-sequenced MM lines and the discovery of a subset defined by loss of
function of the nuclear deubiquitinase BRCA associated protein-1 (BAP1) that
demonstrate heightened sensitivity to TRAIL (tumour necrosis factor-related
apoptosis-inducing ligand). This association is observed across human early
passage MM cultures, mouse xenografts and human tumour explants. We demonstrate
that BAP1 deubiquitinase activity and its association with ASXL1 to form the
Polycomb repressive deubiquitinase complex (PR-DUB) impacts TRAIL sensitivity
implicating transcriptional modulation as an underlying mechanism. Death receptor
agonists are well-tolerated anti-cancer agents demonstrating limited therapeutic
benefit in trials without a targeting biomarker. We identify BAP1 loss-of
function mutations, which are frequent in MM, as a potential genomic
stratification tool for TRAIL sensitivity with immediate and actionable
therapeutic implications.
PMID- 29345618
TI - NECAPs are negative regulators of the AP2 clathrin adaptor complex.
AB - Eukaryotic cells internalize transmembrane receptors via clathrin-mediated
endocytosis, but it remains unclear how the machinery underpinning this process
is regulated. We recently discovered that membrane-associated muniscin proteins
such as FCHo and SGIP initiate endocytosis by converting the AP2 clathrin adaptor
complex to an open, active conformation that is then phosphorylated (Hollopeter
et al., 2014). Here we report that loss of ncap-1, the sole C. elegans gene
encoding an adaptiN Ear-binding Coat-Associated Protein (NECAP), bypasses the
requirement for FCHO-1. Biochemical analyses reveal AP2 accumulates in an open,
phosphorylated state in ncap-1 mutant worms, suggesting NECAPs promote the
closed, inactive conformation of AP2. Consistent with this model, NECAPs
preferentially bind open and phosphorylated forms of AP2 in vitro and localize
with constitutively open AP2 mutants in vivo. NECAPs do not associate with
phosphorylation-defective AP2 mutants, implying that phosphorylation precedes
NECAP recruitment. We propose NECAPs function late in endocytosis to inactivate
AP2.
PMID- 29345619
TI - miR-9 regulates basal ganglia-dependent developmental vocal learning and adult
vocal performance in songbirds.
AB - miR-9 is an evolutionarily conserved miRNA that is abundantly expressed in Area
X, a basal ganglia nucleus required for vocal learning in songbirds. Here, we
report that overexpression of miR-9 in Area X of juvenile zebra finches impairs
developmental vocal learning, resulting in a song with syllable omission, reduced
similarity to the tutor song, and altered acoustic features. miR-9 overexpression
in juveniles also leads to more variable song performance in adulthood, and
abolishes social context-dependent modulation of song variability. We further
show that these behavioral deficits are accompanied by downregulation of FoxP1
and FoxP2, genes that are known to be associated with language impairments, as
well as by disruption of dopamine signaling and widespread changes in the
expression of genes that are important in circuit development and functions.
These findings demonstrate a vital role for miR-9 in basal ganglia function and
vocal communication, suggesting that dysregulation of miR-9 in humans may
contribute to language impairments and related neurodevelopmental disorders.
PMID- 29345621
TI - Circulating Helper T-Cell Subsets and Regulatory T Cells in Patients With Common
Variable Immunodeficiency Without Known Monogenic Disease.
AB - BACKGROUND: Common variable immunodeficiency (CVID) is the most common
symptomatic primary immunodeficiency (PID). It is characterized by heterogeneous
clinical manifestations and defects in B cells and T cells. In the present study,
we investigated helper T (TH) cell subsets and regulatory T (Treg) cells and
their related cytokines and transcription factors in CVID patients with no
definitive genetic diagnosis. METHODS: The study population comprised 13 CVID
patients and 13 healthy controls. Mutation analysis was performed using whole
exome sequencing in CVID patients to rule out monogenic PIDs. TH subsets and Treg
were analyzed using flow cytometry. The expression of determinant cytokines (IFN
gamma, IL-17, IL-22, and IL-10) and cell subset specific transcription factors
was evaluated before and after stimulation. RESULTS: The main clinical
presentations of these patients were infections only and lymphoproliferative
phenotypes. No autoimmune or allergy phenotypes were recorded. The frequencies of
CD4+ T cells, TH17, and Treg cells were significantly reduced in CVID patients;
however, TH1, TH1-like TH17, and TH22 subsets were normal. After stimulation,
expression of retinoic-acid-orphan-receptor-C (RORC), runtrelated transcription
factor 1 (RUNX1), IL17, and IL10 was significantly lower in CVID patients than in
the healthy controls. Moreover, the concentration of IL-17 and IL-10 in the cell
culture supernatants of stimulated CD4+ T cells was lower in CVID patients than
in healthy controls. CONCLUSIONS: Our findings demonstrate that the imbalance of
TH17 and Tregs could be associated with infection and the lymphoproliferative
phenotype in CVID patients without monogenic disorders.
PMID- 29345620
TI - Functional role of the type 1 pilus rod structure in mediating host-pathogen
interactions.
AB - Uropathogenic E. coli (UPEC), which cause urinary tract infections (UTI), utilize
type 1 pili, a chaperone usher pathway (CUP) pilus, to cause UTI and colonize the
gut. The pilus rod, comprised of repeating FimA subunits, provides a structural
scaffold for displaying the tip adhesin, FimH. We solved the 4.2 A resolution
structure of the type 1 pilus rod using cryo-electron microscopy. Residues
forming the interactive surfaces that determine the mechanical properties of the
rod were maintained by selection based on a global alignment of fimA sequences.
We identified mutations that did not alter pilus production in vitro but reduced
the force required to unwind the rod. UPEC expressing these mutant pili were
significantly attenuated in bladder infection and intestinal colonization in
mice. This study elucidates an unappreciated functional role for the molecular
spring-like property of type 1 pilus rods in host-pathogen interactions and
carries important implications for other pilus-mediated diseases.
PMID- 29345622
TI - Position paper on nasal obstruction: evaluation and treatment.
AB - Nasal obstruction (NO) is defined as the subjective perception of discomfort or
difficulty in the passage of air through the nostrils. It is a common reason for
consultation in primary and specialized care and may affect up to 30%-40% of the
population. It affects quality of life (especially sleep) and lowers work
efficiency. The aim of this document is to agree on how to treat NO, establish a
methodology for evaluating and diagnosing it, and define an individualized
approach to its treatment. NO can be unilateral or bilateral, intermittent or
persistent and may be caused by local or systemic factors, which may be
anatomical, inflammatory, neurological, hormonal, functional, environmental, or
pharmacological in origin. Directed study of the medical history and physical
examination are key for diagnosing the specific cause. NO may be evaluated using
subjective assessment tools (visual analog scale, symptom score, standardized
questionnaires) or by objective estimation (active anterior rhinomanometry,
acoustic rhinometry, peak nasal inspiratory flow). Although there is little
correlation between the results, they may be considered complementary and not
exclusive. Assessing the impact on quality of life through questionnaires
standardized according to the underlying disease is also advisable. NO is treated
according to its cause. Treatment is fundamentally pharmacological (topical
and/or systemic) when the etiology is inflammatory or functional. Surgery may be
necessary when medical treatment fails to complement or improve medical treatment
or when other therapeutic approaches are not possible. Combinations of surgical
techniques and medical treatment may be necessary.
PMID- 29345623
TI - Affordable and accurate large-scale hybrid-functional calculations on GPU
accelerated supercomputers.
AB - Performing high accuracy hybrid functional calculations for condensed matter
systems containing a large number of atoms is at present computationally very
demanding or even out of reach if high quality basis sets are used. We present a
highly optimized multiple graphics processing unit implementation of the exact
exchange operator which allows one to perform fast hybrid functional density
functional theory (DFT) calculations with systematic basis sets without
additional approximations for up to a thousand atoms. With this method hybrid DFT
calculations of high quality become accessible on state-of-the-art supercomputers
within a time-to-solution that is of the same order of magnitude as traditional
semilocal-GGA functionals. The method is implemented in a portable open-source
library.
PMID- 29345624
TI - The role of H-bond in the high-pressure chemistry of model molecules.
AB - Pressure is an extraordinary tool to modify direction and strength of
intermolecular interactions with important consequences on the chemical stability
of molecular materials. The decrease of the distance among nearest neighbour
molecules can give rise to reactive configurations reflecting the crystal
arrangement and leading to association processes. In this context, the role of
the H-bonds is very peculiar because their usual strengthening with rising
pressure does not necessarily configure a decrease of the reaction activation
energy but, on the contrary, can give rise to an anomalous stability of the
system. In spite of this central role, the mechanisms by which a chemical
reaction is favoured or prevented by H-bonding under high pressure conditions is
a poorly explored field. Here we review a few studies where the chemical
behaviour of simple molecular systems under static compression was related to the
H-bonding evolution with pressure. These results are able to clarify a wealth of
changes of the chemical and physical properties caused by the strengthening with
pressure of the H-bonding network and provide additional tools to understand the
mechanisms of high-pressure reactivity, a mandatory step to make these synthetic
methods of potential interest for applicative purposes.
PMID- 29345625
TI - The all-optical modulator in dielectric-loaded waveguide with graphene-silicon
heterojunction structure.
AB - All-optical modulators based on graphene show great promise for on-chip optical
interconnects. However, the modulation performance of all-optical modulators is
usually based on the interaction between graphene and the fiber, limiting their
potential in high integration. Based on this point, an all-optical modulator in a
dielectric-loaded waveguide (DLW) with a graphene-silicon heterojunction
structure (GSH) is proposed. The DLW raises the waveguide mode, which provides a
strong light-graphene interaction. Sufficient tuning of the graphene Fermi energy
beyond the Pauli blocking effect is obtained with the presented GSH structure.
Under the modulation light with a wavelength of 532 nm and a power of 60 mW, a
modulation efficiency of 0.0275 dB um-1 is achieved for light with a
communication wavelength of 1.55 um in the experiment. This modulator has the
advantage of having a compact footprint, which may make it a candidate for
achieving a highly integrated all-optical modulator.
PMID- 29345626
TI - Accelerating acquisition strategies for low-frequency conductivity imaging using
MREIT.
AB - We sought to improve efficiency of magnetic resonance electrical impedance
tomography data acquisition so that fast conductivity changes or electric field
variations could be monitored. Undersampling of k-space was used to decrease
acquisition times in spin-echo-based sequences by a factor of two. Full MREIT
data were reconstructed using continuity assumptions and preliminary scans
gathered without current. We found that phase data were reconstructed faithfully
from undersampled data. Conductivity reconstructions of phantom data were also
possible. Therefore, undersampled k-space methods can potentially be used to
accelerate MREIT acquisition. This method could be an advantage in imaging real
time conductivity changes with MREIT.
PMID- 29345627
TI - Large-area synthesis and photoelectric properties of few-layered MoSe2
on molybdenum foils.
AB - Compared with MoS2 and WS2, the selenide analogues have narrower band gaps and
higher electron mobilities, which make them more applicable to real electrical
devices. Besides, few-layered metal selenides have higher electrical
conductivity, carrier mobility and light absorption than the corresponding
monolayers. However, the large-scale and high-quality growth of few-layered metal
selenides remains a significant challenge. Here, we develop a facile method to
grow large-area and highly-crystalline few-layered MoSe2 by directly selenizing
the Mo foil surfaces at 550 oC within 60 min under ambient pressure. The atomic
layers were controllably grown with the thickness between 3.4 and 6 nm which just
met the thickness range required for high-performance electrical devices.
Furthermore, we fabricated a vertical p-n junction photodetector composed of few
layered MoSe2 and p-type silicon, achieving photoresponsivity higher than two
orders of magnitude than that of the reported monolayer counterpart. This
technique provides a feasible approach towards preparing other 2D TMDs for device
applications.
PMID- 29345628
TI - Reversibility and intermediate steps as key tools for the growth of extended
ordered polymers via on-surface synthesis.
AB - Surface-confined polymerization is a bottom-up strategy to create one- and two
dimensional covalent organic nanostructures with a pi-conjugated backbone, which
are suitable to be employed in real-life electronic devices, due to their high
mechanical resistance and electronic charge transport efficiency. This strategy
makes it possible to change the properties of the final nanostructures by a
careful choice of the monomer architecture (i.e. of its constituent atoms and
their spatial arrangement). Several chemical reactions have been proven to form
low-dimensional polymers on surfaces, exploiting a variety of precursors in
combination with metal (e.g. Cu, Ag, Au) and insulating (e.g. NaCl, CaCO3)
surfaces. One of the main challenges of such an approach is to obtain
nanostructures with long-range order, to boost the conductance performances of
these materials. Most of the exploited chemical reactions use irreversible
coupling between the monomers and, as a consequence, the resulting structures
often suffer from poor order and high defect density. This review focuses on the
state-of-the-art surface-confined polymerization reactions, with particular
attention paid to reversible coupling pathways and irreversible processes
including intermediate states, which are key aspects to control to increase the
order of the final nanostructure.
PMID- 29345629
TI - Molecular dynamics based simulations to study the fracture strength of monolayer
graphene oxide.
AB - The aim of this article is to study the effects of functional groups such as
hydroxyl, epoxide and carboxyl on the fracture toughness of graphene. These
functional groups form the backbone of the intrinsic atomic structure of graphene
oxide (GO). Molecular dynamics based simulations were performed in conjunction
with reactive force field parameters to capture the Mode-I fracture toughness of
functionalised graphene. Simulations were performed in stages, to study the
effect of these functional groups, individually as well as all together on the
fracture toughness of GO nanosheets. The molecular dynamics based simulations
performed in this article helps us to conclude that the spatial distribution and
concentration of functional groups significantly affects the fracture behavior of
GO nanosheets.
PMID- 29345630
TI - Completely flat two-dimensional Zn3O2 monolayer with
triangle and pentangle coordinated networks.
AB - Two-dimensional (2D) materials with strictly planar hyper-coordinated motifs are
of great importance in fundamental science and potential applications but
extremely rare. Here we theoretically design a novel 2D IIB-VIA inorganic system,
namely Zn3O2 monolayer, by comprehensive first-principles computations. This
Zn3O2 monolayer is composed from highly symmetrical tri-coordinated oxygen and
tetra-coordinated zinc, featuring planar and peculiar triangle and pentangle
combined bonded network. The newly predicted Zn3O2 monolayer possesses excellent
dynamic and thermal stabilities and is also the lowest-energy structure of its 2D
space indicated by particle swarm search, supporting its experimentally synthetic
viability. A relatively wide band gap of 4.46 eV endows it potential applications
in electronics and optoelectronics. The present findings provide a new field of
hyper-coordinated 2D nanomaterials for study.
PMID- 29345631
TI - Role of four-fermion interaction and impurity in the states of two-dimensional
semi-Dirac materials.
AB - We study the effects of four-fermion interaction and impurity on the low-energy
states of 2D semi-Dirac materials by virtue of the unbiased renormalization group
approach. The coupled flow equations that govern the energy-dependent evolutions
of all correlated interaction parameters are derived after taking into account
one-loop corrections from the interplay between four-fermion interaction and
impurity. Whether and how four-fermion interaction and impurity influence the low
energy properties of 2D semi-Dirac materials are discreetly explored and
addressed attentively. After carrying out the standard renormalization group
analysis, we find that both trivial insulating and nontrivial semimetal states
are qualitatively stable against all four kinds of four-fermion interactions.
However, while switching on both four-fermion interaction and impurity, certain
insulator-semimetal phase transitions and the distance of Dirac nodal points can
be respectively induced and modified due to their strong interplay and intimate
competition. Moreover, several non-Fermi liquid behaviors that deviate from the
conventional Fermi liquids are exhibited at the lowest-energy limit.
PMID- 29345632
TI - Brain-machine interfaces for controlling lower-limb powered robotic systems.
AB - OBJECTIVE: Lower-limb, powered robotics systems such as exoskeletons and orthoses
have emerged as novel robotic interventions to assist or rehabilitate people with
walking disabilities. These devices are generally controlled by certain physical
maneuvers, for example pressing buttons or shifting body weight. Although
effective, these control schemes are not what humans naturally use. The usability
and clinical relevance of these robotics systems could be further enhanced by
brain-machine interfaces (BMIs). A number of preliminary studies have been
published on this topic, but a systematic understanding of the experimental
design, tasks, and performance of BMI-exoskeleton systems for restoration of gait
is lacking. APPROACH: To address this gap, we applied standard systematic review
methodology for a literature search in PubMed and EMBASE databases and identified
11 studies involving BMI-robotics systems. The devices, user population, input
and output of the BMIs and robot systems respectively, neural features, decoders,
denoising techniques, and system performance were reviewed and compared. MAIN
RESULTS: Results showed BMIs classifying walk versus stand tasks are the most
common. The results also indicate that electroencephalography (EEG) is the only
recording method for humans. Performance was not clearly presented in most of the
studies. Several challenges were summarized, including EEG denoising, safety,
responsiveness and others. SIGNIFICANCE: We conclude that lower-body powered
exoskeletons with automated gait intention detection based on BMIs open new
possibilities in the assistance and rehabilitation fields, although the current
performance, clinical benefits and several key challenging issues indicate that
additional research and development is required to deploy these systems in the
clinic and at home. Moreover, rigorous EEG denoising techniques, suitable
performance metrics, consistent trial reporting, and more clinical trials are
needed to advance the field.
PMID- 29345633
TI - Impacts of an Exercise Program and Motivational Telephone Counseling on Health
Related Quality of Life in People With Parkinson's Disease.
AB - PURPOSE: The purpose of this study was to test the effects of group exercise and
telephone counseling on physical and psychosocial health in people with
Parkinson's disease (PD). DESIGN: This was a quasiexperimental study with a
nonequivalent control group. METHODS: This study took place in Seoul, South
Korea. Twenty-two and 20 subjects participated in the intervention and comparison
groups, respectively. The intervention group performed group exercises twice a
week and received motivational telephone counseling every 2 weeks for 12 weeks.
FINDINGS: Significant effects of the intervention were found in overall health
related quality of life (HRQOL; p = .012) and in the following HRQOL dimensions:
stigma (p = .026), social function (p = .003), cognition (p = .028), and
communication (p = .014). No other variables such as activities of daily living,
functional fitness, and depression exhibited statistically significant effects.
CONCLUSION/CLINICAL RELEVANCE: These results indicate that group exercise with
telephone counseling positively affects some aspects of HRQOL in PD patients.
PMID- 29345634
TI - Erratum.
PMID- 29345635
TI - Genetic risk, dysbiosis, and treatment stratification using host genome and gut
microbiome in inflammatory bowel disease.
AB - OBJECTIVES: Inflammatory bowel diseases (IBD), comprised of Crohn's disease (CD)
and ulcerative colitis (UC), are characterized by a complex pathophysiology that
is thought to result from an aberrant immune response to a dysbiotic luminal
microbiota in genetically susceptible individuals. New technologies support the
joint assessment of host-microbiome interaction. METHODS: Using whole genome
sequencing and shotgun metagenomics, we studied the clinical features, host
genome, and stool microbial metagenome of 85 IBD patients, and compared the
results to 146 control individuals. Genetic risk scores, computed on 159 single
nucleotide variants, and human leukocyte antigen (HLA) types differentiated IBD
patients from healthy controls. RESULTS: Genetic risk was associated with the
need for use of biologics in IBD and, modestly, with the composition of the gut
microbiome. As compared with healthy controls, IBD patients had hallmarks of
stool microbiome dysbiosis, with loss of a diversified core microbiome,
enrichment and depletion of specific bacteria, and enrichment of bacterial
virulence factors. CONCLUSIONS: We show that genetic risk may have a role in
early risk stratification in the care of IBD patients and propose that expression
of virulence factors in a dysbiotic microbiome may contribute to pathogenesis in
IBD.
PMID- 29345637
TI - Structural basis of RNA polymerase III transcription initiation.
AB - RNA polymerase (Pol) III transcribes essential non-coding RNAs, including the
entire pool of transfer RNAs, the 5S ribosomal RNA and the U6 spliceosomal RNA,
and is often deregulated in cancer cells. The initiation of gene transcription by
Pol III requires the activity of the transcription factor TFIIIB to form a
transcriptionally active Pol III preinitiation complex (PIC). Here we present
electron microscopy reconstructions of Pol III PICs at 3.4-4.0 A and a
reconstruction of unbound apo-Pol III at 3.1 A. TFIIIB fully encircles the DNA
and restructures Pol III. In particular, binding of the TFIIIB subunit Bdp1
rearranges the Pol III-specific subunits C37 and C34, thereby promoting DNA
opening. The unwound DNA directly contacts both sides of the Pol III cleft.
Topologically, the Pol III PIC resembles the Pol II PIC, whereas the Pol I PIC is
more divergent. The structures presented unravel the molecular mechanisms
underlying the first steps of Pol III transcription and also the general
conserved mechanisms of gene transcription initiation.
PMID- 29345636
TI - Promoting the accumulation of tumor-specific T cells in tumor tissues by
dendritic cell vaccines and chemokine-modulating agents.
AB - This protocol describes how to induce large numbers of tumor-specific cytotoxic T
cells (CTLs) in the spleens and lymph nodes of mice receiving dendritic cell (DC)
vaccines and how to modulate tumor microenvironments (TMEs) to ensure effective
homing of the vaccination-induced CTLs to tumor tissues. We also describe how to
evaluate the numbers of tumor-specific CTLs within tumors. The protocol contains
detailed information describing how to generate a specialized DC vaccine with
augmented ability to induce tumor-specific CTLs. We also describe methods to
modulate the production of chemokines in the TME and show how to quantify tumor
specific CTLs in the lymphoid organs and tumor tissues of mice receiving
different treatments. The combined experimental procedure, including tumor
implantation, DC vaccine generation, chemokine-modulating (CKM) approaches, and
the analyses of tumor-specific systemic and intratumoral immunity is performed
over 30-40 d. The presented ELISpot-based ex vivo CTL assay takes 6 h to set up
and 5 h to develop. In contrast to other methods of evaluating tumor-specific
immunity in tumor tissues, our approach allows detection of intratumoral T-cell
responses to nonmanipulated weakly immunogenic cancers. This detection method can
be performed using basic laboratory skills, and facilitates the development and
preclinical evaluation of new immunotherapies.
PMID- 29345638
TI - Molecular mechanism of promoter opening by RNA polymerase III.
AB - RNA polymerase III (Pol III) and transcription factor IIIB (TFIIIB) assemble
together on different promoter types to initiate the transcription of small,
structured RNAs. Here we present structures of Pol III preinitiation complexes,
comprising the 17-subunit Pol III and the heterotrimeric transcription factor
TFIIIB, bound to a natural promoter in different functional states. Electron cryo
microscopy reconstructions, varying from 3.7 A to 5.5 A resolution, include two
early intermediates in which the DNA duplex is closed, an open DNA complex, and
an initially transcribing complex with RNA in the active site. Our structures
reveal an extremely tight, multivalent interaction between TFIIIB and promoter
DNA, and explain how TFIIIB recruits Pol III. Together, TFIIIB and Pol III
subunit C37 activate the intrinsic transcription factor-like activity of the Pol
III-specific heterotrimer to initiate the melting of double-stranded DNA, in a
mechanism similar to that of the Pol II system.
PMID- 29345640
TI - Strategy for making safer opioids bolstered.
PMID- 29345639
TI - Emergent constraint on equilibrium climate sensitivity from global temperature
variability.
AB - Equilibrium climate sensitivity (ECS) remains one of the most important unknowns
in climate change science. ECS is defined as the global mean warming that would
occur if the atmospheric carbon dioxide (CO2) concentration were instantly
doubled and the climate were then brought to equilibrium with that new level of
CO2. Despite its rather idealized definition, ECS has continuing relevance for
international climate change agreements, which are often framed in terms of
stabilization of global warming relative to the pre-industrial climate. However,
the 'likely' range of ECS as stated by the Intergovernmental Panel on Climate
Change (IPCC) has remained at 1.5-4.5 degrees Celsius for more than 25 years. The
possibility of a value of ECS towards the upper end of this range reduces the
feasibility of avoiding 2 degrees Celsius of global warming, as required by the
Paris Agreement. Here we present a new emergent constraint on ECS that yields a
central estimate of 2.8 degrees Celsius with 66 per cent confidence limits
(equivalent to the IPCC 'likely' range) of 2.2-3.4 degrees Celsius. Our approach
is to focus on the variability of temperature about long-term historical warming,
rather than on the warming trend itself. We use an ensemble of climate models to
define an emergent relationship between ECS and a theoretically informed metric
of global temperature variability. This metric of variability can also be
calculated from observational records of global warming, which enables tighter
constraints to be placed on ECS, reducing the probability of ECS being less than
1.5 degrees Celsius to less than 3 per cent, and the probability of ECS exceeding
4.5 degrees Celsius to less than 1 per cent.
PMID- 29345642
TI - Support for US postdocs is growing slowly.
PMID- 29345641
TI - The dark side of light: how artificial lighting is harming the natural world.
PMID- 29345644
TI - China's plan to recruit talented researchers.
PMID- 29345645
TI - Integrity must underpin quality of statistics.
PMID- 29345646
TI - Scientists in China regenerate lens in human eye.
PMID- 29345647
TI - Laws are not the only way to boost immunization.
PMID- 29345648
TI - Fossilized pregnant dinosaur discovered in southern China.
PMID- 29345649
TI - NASA test proves pulsars can function as a celestial GPS.
PMID- 29345650
TI - Synthetic species made to shun sex with wild organisms.
PMID- 29345651
TI - US i mmigration fight heightens legal limbo for young 'Dreamer' scientists.
PMID- 29345652
TI - Revamped collider hunts for cracks in the fundamental theory of physics.
PMID- 29345653
TI - Make lighting healthier.
PMID- 29345655
TI - China enters the battle for AI talent.
PMID- 29345654
TI - Ben Barres (1954-2017).
PMID- 29345656
TI - Intelligence conference, rainforest park and oil-spill fears.
PMID- 29345657
TI - Putting China's science on the map.
PMID- 29345658
TI - How a biotech entrepreneur benefits from splitting time between China and the
United States.
PMID- 29345659
TI - Returning to a revitalized China after research abroad.
PMID- 29345660
TI - Pathogens boosted by food additive.
PMID- 29345661
TI - How private-sector research is changing China.
PMID- 29345662
TI - Maths strikes a blow for democracy.
PMID- 29345663
TI - Don't misrepresent link between bats and SARS.
PMID- 29345664
TI - Could baby's first bacteria take root before birth?
PMID- 29345665
TI - How to find a job in China.
PMID- 29345666
TI - Limitless translation limits translation.
PMID- 29345667
TI - Showcase scientists from the global south.
PMID- 29345668
TI - The ups and downs of moving to China.
PMID- 29345669
TI - Why China needs your scientific expertise.
PMID- 29345671
TI - Why an Italian astrophysicist decided to move to Shanghai.
PMID- 29345672
TI - Train robots to self-certify their safe operation.
PMID- 29345673
TI - China's AI dreams.
PMID- 29345675
TI - The Fields Medal should return to its roots.
PMID- 29345674
TI - Career guide: China.
PMID- 29345677
TI - Mice learn to avoid the rat race.
PMID- 29345676
TI - Research kudos does not need a price tag.
PMID- 29345679
TI - Fixing statistics is more than a technical issue.
PMID- 29345680
TI - Should we steer clear of the winner-takes-all approach?
PMID- 29345678
TI - China needs to listen to its researchers to become a scientific superpower.
PMID- 29345681
TI - Biotech booms in China.
PMID- 29345683
TI - Homing in on a key factor of climate change.
PMID- 29345684
TI - MSH6 and PMS2 germ-line pathogenic variants implicated in Lynch syndrome are
associated with breast cancer.
AB - PURPOSE: An association of Lynch syndrome (LS) with breast cancer has been long
suspected; however, there have been insufficient data to address this question
for each of the LS genes individually. METHODS: We conducted a retrospective
review of personal and family history in 423 women with pathogenic or likely
pathogenic germ-line variants in MLH1 (N = 65), MSH2 (N = 94), MSH6 (N = 140), or
PMS2 (N = 124) identified via clinical multigene hereditary cancer testing.
Standard incidence ratios (SIRs) of breast cancer were calculated by comparing
breast cancer frequencies in our study population with those in the general
population (Surveillance, Epidemiology, and End Results 18 data). RESULTS: When
evaluating by gene, the age-standardized breast cancer risks for MSH6 (SIR =
2.11; 95% confidence interval (CI), 1.56-2.86) and PMS2 (SIR = 2.92; 95% CI, 2.17
3.92) were associated with a statistically significant risk for breast cancer
whereas no association was observed for MLH1 (SIR = 0.87; 95% CI, 0.42-1.83) or
MSH2 (SIR = 1.22; 95% CI, 0.72-2.06). CONCLUSION: Our data demonstrate that two
LS genes, MSH6 and PMS2, are associated with an increased risk for breast cancer
and should be considered when ordering genetic testing for individuals who have a
personal and/or family history of breast cancer.
PMID- 29345685
TI - Imaging: Pacemakers, ICDs, and MRI.
PMID- 29345687
TI - Interventional cardiology: 3D printing of personalized implants for left atrial
appendage occlusion.
PMID- 29345686
TI - Reversal agents for non-vitamin K antagonist oral anticoagulants.
AB - The non-vitamin K antagonist oral anticoagulants (NOACs) include dabigatran,
which inhibits thrombin, and apixaban, betrixaban, edoxaban, and rivaroxaban,
which inhibit coagulation factor Xa. Although clinical studies of NOACs were
conducted without antidotes, patient outcomes with major bleeding when receiving
NOACs were no worse than those in patients treated with a vitamin K antagonist.
Nonetheless, in patients with life-threatening bleeding or requiring urgent
surgery, the capacity for rapid NOAC reversal is likely to increase patient
safety. Three NOAC reversal agents are in various stages of development:
idarucizumab, a specific reversal agent for dabigatran; andexanet alfa, which
reverses factor Xa inhibitors; and ciraparantag, which is purported to reverse
all NOACs. Idarucizumab is licensed in many countries, andexanet is under
consideration by regulatory agencies, and ciraparantag is undergoing phase III
evaluation. In the absence of licensed reversal agents for the oral factor Xa
inhibitors, prothrombin complex concentrates are often used in patients taking
these agents who present with life-threatening bleeding. In this Review, we
summarize the approved indications for the NOACs, outline how to measure their
anticoagulant effects, describe the mechanism of action of the reversal
strategies, assess the preclinical and clinical data supporting their use,
provide guidance on potential indications for reversal, and offer a management
approach for patients treated with NOACs who present with serious bleeding or
require urgent surgery.
PMID- 29345688
TI - Corrigendum.
AB - [This corrects the article DOI: 10.1177/1757177417695647.].
PMID- 29345689
TI - Concerns with conclusions in the article by Sherwood et al 'Key differences
between 13 KRAS mutation detection technologies and their relevance for clinical
practice'.
PMID- 29345690
TI - Clozapine-induced myocarditis.
AB - Approved in 1989 for the management of treatment-resistant schizophrenia,
Clozapine is a last-line atypical antipsychotic drug used with increasing
frequency. In addition to its well-known side effect of agranulocytosis, this
drug also carries with it rare but serious adverse cardiovascular risk of
myocarditis. We present a patient on Clozapine who was admitted to the cardiology
service with chest pain, ST segment elevations and elevated troponin concerning
for acute myocardial infarction. Evaluation with imaging revealed decreased left
ventricular function, however, no coronary artery disease was present on
catheterization; findings consistent with a diagnosis of myocarditis. Subsequent
discontinuation of the patient's Clozapine and initiation of brief supportive
medical therapy resulted in full recovery of systolic left ventricular function.
Given the potential cardiovascular mortality risk, it is important for physicians
on cardiology services caring for psychiatric patients to be aware of the
presentation of symptoms, diagnostic findings and management of Clozapine induced
myocarditis.
PMID- 29345691
TI - Re: Goel A. Research training during residency. Indian J Urol 2017;33:257-8.
PMID- 29345693
TI - Corrigendum.
AB - [This corrects the article DOI: 10.1177/1757177417720999.].
PMID- 29345692
TI - Erratum: Publisher's Note: "Implications of short time scale dynamics on long
time processes" (Struct. Dyn. 4, 061507 (2017)].
AB - [This corrects the article DOI: 10.1063/1.4996448.].
PMID- 29345694
TI - Erratum to: Physical fitness of Ghanaian physiotherapists and its correlation
with age and exercise engagement: a pilot study.
AB - [This corrects the article DOI: 10.1186/s40945-016-0016-2.].
PMID- 29345695
TI - Erratum: Kini Bailur J, Mehta S, Zhang L, et al. Changes in bone marrow innate
lymphoid cell subsets in monoclonal gammopathy: target for IMiD therapy. Blood
Adv. 2017;1(25):2343-2347.
AB - [This corrects the article DOI: 10.1182/bloodadvances.2017012732.].
PMID- 29345697
TI - Re: Singh A et al. Robot-assisted retroperitoneal lymph node dissection:
Feasibility and outcome in postchemotherapy residual mass in testicular cancer.
Indian J Urol 2017;33:304-9.
PMID- 29345696
TI - Antiemetic efficacy and safety of granisetron or palonosetron alone and in
combination with a corticosteroid for ABVD therapy-induced nausea and vomiting.
AB - Background: Antiemetic effects and safety of granisetron or palonosetron alone
and in combination with a corticosteroid against chemotherapy-induced nausea and
vomiting (CINV) were retrospectively evaluated in patients with Hodgkin lymphoma
receiving adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) therapy.
Methods: A total of 39 patients were eligible for this study. Before ABVD
therapy, granisetron or palonosetron was intravenously administered with or
without a corticosteroid (dexamethasone or hydrocortisone) and aprepitant. The
proportions of patients with complete control (CC) during the overall (0-120 h
after the start of ABVD therapy), acute (0-24 h) and delayed (24-120 h) phases
were evaluated. CC was defined as no vomiting and no use of antiemetic rescue
medication with only grade 0-1 nausea. Results: Granisetron and palonosetron were
administered in 21 and 18 patients, respectively. The CC rate during the acute,
delayed and overall phases was not statistically different between the two
groups. The CINV was completely controlled during overall phase in 58.3% of
patients receiving granisetron or palonosetron in combination with a
corticosteroid, whereas in 11.1% of those without co-treatment of a
corticosteroid (P < 0.05). There were significantly higher frequencies of
anorexia, leucopenia and neutropenia in the palonosetron group. There is a
statistically significant difference in the frequency of febrile neutropenia
between presence and absence of a corticosteroid (p = 0.024). Conclusion: These
findings suggested that a combination use of a corticosteroid with a 5-HT3
receptor antagonist was preferable for CINV control in patients with Hodgkin
lymphoma receiving ABVD therapy, although the careful management of febrile
neutropenia is required. Trial registration: The study approval numbers in the
institution; 24-12 and 24-359. Registered April 17, 2012 and June 21, 2012.
PMID- 29345698
TI - Aerogen bonds formed between AeOF2 (Ae = Kr, Xe) and diazines: comparisons
between sigma-hole and pi-hole complexes.
AB - The interaction between KrOF2 or XeOF2 and the 1,2, 1,3, and 1,4 diazines is
characterized chiefly by a Kr/XeN aerogen bond, as deduced from ab initio
calculations. The most stable dimers take advantage of the sigma-hole on the
aerogen atom, wherein the two molecules lie in the same plane. The interaction is
quite strong, as much as 18 kcal mol-1. A second class of dimer geometry utilizes
the pi-hole above the aerogen atom in an approximate perpendicular arrangement of
the two monomers; these structures are not as strongly bound: 6-8 kcal mol-1.
Both sorts of dimers contain auxiliary CHF H-bonds which contribute to their
stability, but even with their removal, the aerogen bond energy remains as high
as 14 kcal mol-1. The nature and strength of each specific interaction is
confirmed and quantified by AIM, NCI, NBO, and electron density shift patterns.
There is not a great deal of sensitivity to the identity of either the aerogen
atom or the position of the two N atoms in the diazine.
PMID- 29345699
TI - Theoretical investigations on the unsymmetrical effect of beta-link Zn-porphyrin
sensitizers on the performance for dye-sensitized solar cells.
AB - Dye sensitizers play an important role in dye-sensitized solar cells (DSSCs). As
a promising strategy for the design of novel porphyrin sensitizers, the
asymmetric modification of the porphyrin ring to meso-link porphyrin sensitizer
has emerged in recent years, which can improve the light-harvesting properties
and enhance the electron distribution. In this work, in order to reveal the
essence of the effect of unsymmetrical substitution on the performance of beta
link porphyrin dyes in DSSCs, four kinds of common beta-link porphyrin dyes with
different structures are calculated by using density functional theory (DFT) and
time-dependent density functional theory (TD-DFT). The electronic structures and
optical properties of these studied dyes in dimethylformamide (DMF) are also
investigated. The key parameters of the short-circuit current density (Jsc),
including light harvesting efficiency (LHE), electron injection driving force
(DeltaGinject), and intra-molecular charge transfer (ICT) are discussed in
detail. In addition, the periodic DFT calculations in the dye-TiO2 systems are
also employed to investigate the geometrical and electronic injection process of
the different connection types of these studied dyes adsorbed on the periodic
TiO2 model with an exposed anatase (101) surface. We expect the present study
would deepen the understanding of the alternative function of unsymmetrical
substitution and may contribute to future DSSC design.
PMID- 29345700
TI - Abnormal separation of the silicon-oxygen bond in the liquid layering transition
of silicon dioxide in a nanoslit.
AB - We investigated the unusual layering transition (LT) in quasi-2D liquid silicon
dioxide (SiO2) confined in a nanoslit. Our results indicate that the slit size
and pressure induce the abnormal LT in liquid SiO2, accompanied by a rapid change
in the density, diffusion coefficient, pair correlation function and average
potential energy. The silicon and oxygen atoms are almost completely separated
under the extremely strong confinement effect, which is the characteristic
feature of the LT. The negative slope of the LT lines in the phase diagram at
different pressures suggests that a confinement-induced LT occurs at high
pressure and a pressure-induced LT occurs at low pressure.
PMID- 29345701
TI - Effects of particle size and annealing on plasmon-induced charge separation at
self-assembled gold nanoparticle arrays.
AB - Two-dimensional periodic Au nanoparticle arrays were constructed on TiO2 thin
films by a micelle lithography method and seed-mediated photoelectrochemical
growth. Their adjustable interparticle distance allows investigation of a
particle size effect on plasmon-induced charge separation (PICS) efficiencies
without interference from particle aggregation or plasmon coupling. External or
internal PICS efficiencies were found to increase and decrease, respectively,
with an increase in particle diameter from 25 to 38 nm. Improvement of the
contact between Au nanoparticles and TiO2 by annealing enhanced the intensity of
a plasmonic interface mode and both external and internal PICS efficiencies.
PMID- 29345702
TI - Assessing the consumption of berries and associated factors in the United States
using the National Health and Nutrition Examination Survey (NHANES), 2007-2012.
AB - Intake of berries was assessed relative to other fruit and fruit juices and total
fruit intake in the U.S. population age 2 years and older using the National
Health and Nutrition Examination Survey, 2007-2012. Average daily intake of total
fruit was about 1 cup, and berries comprised approximately 10% of total fruit
consumption. Only 18% of the population met the recommendation of at least 2 cups
of fruit per day. Children ages 2 to 5 years consumed the most total fruit of
which about half was juice and 4% of which was berries. Among adults, the highest
berry consumption was by those who were 65 years and older, non-Hispanic White,
and had the highest education and income levels. Use of the Nutrition Facts panel
and ingredient labeling was associated with greater total fruit and berry intake.
Those who were aware of an amount of fruit that is associated with good health
and of dietary guidance in general and those who had fruit available in the home
consumed about twice as much berries as others. Fruit intake remains below
recommendations in the U.S.; berry intake is particularly low. Behavioral
indicators provided insight on how fruit and berry consumption might be
increased.
PMID- 29345703
TI - Controllable colloidal synthesis of anisotropic tin dichalcogenide nanocrystals
for thin film thermoelectrics.
AB - Tin chalcogenides have shown promise in applications including energy storage,
optoelectronics, photovoltaics, and thermoelectrics. Here, we present a colloidal
synthesis strategy to produce tin dichalcogenide nanocrystals (NCs) with
controllable stoichiometry, vacancies, shape, and crystal structure. Compared
with previously reported methods, we use less expensive precursors, such as
tin(iv) chloride and sulfur or selenium powder, to produce tin(iv) chalcogenide
NCs. SnS2 and SnSe2 NCs with novel NC morphologies including SnS2
nanoflowers/nanoflakes, SnSe2 nanosheets with circular and hexagonal shapes, as
well as mixtures of nanospheres and nanoflakes were prepared by varying the
solvents and anion precursors. We were also able to reduce tin(iv) to tin(ii) to
produce tin(ii) chalcogenide NCs. The corresponding thin films were prepared by
spin-coating, followed by post-treatment to study their thermoelectric
properties. Room temperature Seebeck coefficients of -150 MUV K-1 and -126 MUV K
1 were measured for SnS2 and SnSe2 films, demonstrating their promise as thin
film thermoelectric materials.
PMID- 29345704
TI - Hierarchical core-shell structures of P-Ni(OH)2 rods@MnO2 nanosheets as high
performance cathode materials for asymmetric supercapacitors.
AB - The hierarchical porous structure with phosphorus-doped Ni(OH)2 (P-Ni(OH)2) rods
as the core and MnO2 nanosheets as the shell is fabricated directly by growth on
a three-dimensional (3D) flexible Ni foam (NF) via a two-step hydrothermal
process. As a binder-free electrode material, this unique hybrid structure
exhibits excellent electrochemical properties, including an ultrahigh areal
capacitance of 5.75 F cm-2 at a current density of 2 mA cm-2 and great cyclic
stability without capacitance loss at a current density of 20 mA cm-2 after 10
000 cycles. Moreover, an all-solid-state asymmetric supercapacitor (AAS) based on
a P-Ni(OH)2@MnO2 hybrid structure on Ni foam as the cathode and activated carbon
(AC) as the anode is successfully assembled to enhance value the electrochemical
properties. The AAS device also shows excellent electrochemical properties
including a large potential window of 0~1.6 V, an areal capacitance is 911.3 mF
cm-2 at a current density of 1 mA cm-2 and long-term cycling performance.
Meanwhile, the AAS device also delivers a high energy density of 0.324 mW h cm-2
at a power density of 0.8 mW cm-2; and can easily light colorful light-emitting
diode (LED) lights, suggesting that 3D P-Ni(OH)2@MnO2 hybrid composite has
promising potential for practical use in high-performance supercapacitors.
PMID- 29345705
TI - Contact mechanics for polydimethylsiloxane: from liquid to solid.
AB - Adhesion between a glass ball and a polydimethylsiloxane (PDMS) sample is
dependent on the PDMS cross-link density, and the transformation of the material
from the uncrosslinked liquid state to the fully crosslinked solid state is
investigated in this study. The physical picture reflected a gradual transition
from capillary forces driven contact mechanics to the classical Johnson-Kendall
Roberts (JKR)-type contact mechanics. PDMS was produced by mixing the base fluid
and a cross-linker at a ratio of 10 : 1 and allowed to slowly cross-link at room
temperature with simultaneous measurement of the ball-PDMS interaction force. The
PDMS sample was in the liquid state during the first ~16 hours, and in this case
the ball-PDMS interaction was purely adhesive, i.e., no repulsive interaction was
observed. Later at the PDMS gel-point the cross-linked PDMS clusters percolate,
converting the fluid into a soft (fluid-filled) poroelastic solid. In the
transition period, PDMS appears similar to pressure-sensitive adhesives. There we
observe so-called "stringing" and permanent deformation of the material impacted
by the ball. At room temperature, it takes more than ~100 hours for PDMS to fully
cross-link that can be confirmed by the comparison with the earlier-studied
reference PDMS produced at elevated temperatures.
PMID- 29345706
TI - Tuning the nucleophilicity of electron-rich diborane(4) compounds with bridging
guanidinate substituents by substitution.
AB - Diborane(4) compounds are versatile reagents in synthetic chemistry. Generally,
diboranes(4) with sp2-hybridized boron atoms react as electrophiles. By contrast,
the chemistry of nucleophilic diborane(4) compounds with two sp3-hybridized boron
atoms is very much underdeveloped. In this work, we systematically vary the
substituents of electron-rich diborane(4) compounds with bridging guanidinate
substituents. In this way, five new diboranes are synthesized and fully
characterized. Using quantum chemical computations, we show that the electronic
properties and reactivity of these compounds can be rationally varied by the
choice of substituents. The HOMO energies, adiabatic ionization energies and
proton affinities are considered as parameters to compare the chemical properties
of these unusual compounds.
PMID- 29345709
TI - Chain conformation of poly(acrylic acid)-graft-poly(ethylene oxide)-graft-dodecyl
in solution: an anomalous counter-ions condensation.
AB - A dielectric spectroscopy study on a polyelectrolyte in aqueous solutions, which
contains hydrophobic groups in part of the side chains poly(acrylic acid)-graft
poly(ethylene oxide)-graft-dodecyl (PAA-g-PEO-g-dodecyl) is reported. A refined
double layer polarization model was proposed to analyze the double dielectric
relaxations in the dielectric spectra. Various electrical and structural
parameters of the copolymers were obtained. Besides the crossover concentration,
another turning point around 4 mg mL-1 was identified through the analysis of all
the dielectrical parameters including dielectric increment, relaxation time and
correlation length. According to the scaling relationship between the correlation
length and concentration, a necklace-like structure was predicted. In addition, 4
mg mL-1 was proven to be the transition point between string-controlling with
bead-controlling structure of the chains. In addition, the fraction of effective
charges on the chains was illustrated by Ito's counter-ions fluctuation theory,
as well as its linear dependence relationship with the zeta potential. Meanwhile,
the counter-ions condensation behavior was consistent with the avalanche-like
trend, which was predicted by theory for a hydrophobic polyelectrolyte with a
necklace conformation. The results demonstrated that the electrostatic
interactions were the main driving force of the necklace-like structure with
pendant globules when the string-controlling structure was below 4 mg mL-1. While
hydrophobic interactions are the main driving force of the structure of bead
controlling above 4 mg mL-1.
PMID- 29345707
TI - Synthesis and characterization of a photocleavable collagen-like peptide.
AB - A 34-amino acid long collagen-like peptide rich in proline, hydroxyproline, and
glycine, and with four photoreactive N-acyl-7-nitroindoline units incorporated
into the peptide backbone was synthesized by on-resin fragment condensation. Its
circular dichroism supports a stable triple helix structure. The built-in
photochemical function enables the decomposition of the peptide into small
peptide fragments by illumination with UV light of 350 nm in aqueous solution.
Illumination of a thin film of the peptide, or a thin film of a photoreactive
amino acid model compound containing a 5-bromo-7-nitroindoline moiety, with
femtosecond laser light at 710 nm allows for the creation of well-resolved
micropatterns. The cytocompatibility of the peptide was demonstrated using human
mesenchymal stem cells and mouse embryonic fibroblasts. Our data show that the
full-length peptide is cytocompatible as it can support cell growth and maintain
cell viability. In contrast, the small peptide fragments created by photolysis
are somewhat cytotoxic and therefore less cytocompatible. These data suggest that
biomimetic collagen-like photoreactive peptides could potentially be used for
growing cells in 2D micropatterns based on patterns generated by photolysis prior
to cell growth.
PMID- 29345708
TI - Triphenylstannyl((arylimino)methyl)benzoates with selective potency that induce
G1 and G2/M cell cycle arrest and trigger apoptosis via ROS in human cervical
cancer cells.
AB - Metal complexes with organelle specificity and potent but selective cytotoxicity
are highly desirable. A novel series of triphenylstannyl 4
((arylimino)methyl)benzoates (2-8) were obtained by the reactions of
triphenylstannyl 4-formylbenzoate [Ph3Sn(L1)] 1 with primary aromatic amines. Two
representative compounds (10, 11) were also synthesized by reacting aqua
triphenylstannyl 2-formylbenzoate [Ph3Sn(L9)(H2O)] (9) with aniline and p
fluoroaniline, respectively. These compounds were characterized by elemental
analysis, IR and 1H, 13C and 119Sn NMR spectroscopy, as well as single-crystal X
ray diffraction for compounds 5, 7-11 and three pro-ligands. The in vitro
cytotoxic activities of 1-11 were assessed using the MTT tetrazolium dye assay
against HeLa (human cervical) and MDA-MB-231 (breast) cancer cells, with IC50
values revealing high activity. Compared to cisplatin, compounds 1-11 exhibited
enhanced cytotoxic efficacy, indicating their potential as potent anticancer
agents. Among these, 1 and 5 demonstrated maximum inhibition in HeLa cells, with
negligible effect on normal human embryonic kidney (HEK) cells. The combined
results of the DCFH-DA dye and Hoechst 33342/PI nuclear staining assays, along
with flow cytometry analysis, show that they possess a dual mode of action: They
induced apoptotic cell death, attributable to the tin-assisted generation of
reactive oxygen species. Cell cycle analyses indicated that compounds 1 and 5
exhibit cell growth inhibition and may cause turbulences in the G1 and G2/M
phases.
PMID- 29345710
TI - Small degree of anisotropic wetting on self-similar hierarchical wrinkled
surfaces.
AB - We studied the wetting behavior of multiscale self-similar hierarchical wrinkled
surfaces. The hierarchical surface was fabricated on poly(dimethylsiloxane)
(PDMS) substrates by manipulating the sequential strain release and combined
plasma/ultraviolet ozone (UVO) treatment. The generated structured surface shows
an independently controlled dual-scale roughness with level-1 small-wavelength
wrinkles (wavelength of 700-1500 nm and amplitude of 50-500 nm) resting on level
2 large-wavelength wrinkles (wavelength of 15-35 MUm and amplitude of 3.5-5 MUm),
as well as accompanying orthogonal cracks. By tuning the aspect ratio of
hierarchical wrinkles, the degree of wetting anisotropy in hierarchical wrinkled
surfaces, defined as the contact angle difference between the parallel and
perpendicular directions to the wrinkle grooves, is found to change between 3
degrees and 9 degrees . Through both experimental characterization (confocal
fluorescence imaging) and theoretical analyses, we showed that the wetting state
in the hierarchical wrinkled surface is in the Wenzel wetting state. We found
that the measured apparent contact angle is larger than the theoretically
predicted Wenzel contact angle, which is found to be attributed to the three
phase contact line pinning effect of both wrinkles and cracks that generates
energetic barriers during the contact line motion. This is evidenced by the
observed sudden drop of over 20 degrees in the static contact angles along both
perpendicular and parallel directions after slight vibration perturbation.
Finally, we concluded that the observed small degree of wetting anisotropy in the
hierarchical wrinkled surfaces mainly arises from the competition between
orthogonal wrinkles and cracks in the contact line pinning.
PMID- 29345711
TI - Direct access to spirobiisoxazoline via the double 1,3-dipolar cycloaddition of
nitrile oxide with allenoate.
AB - The double [3 + 2]-cycloadditions between nitrile oxides and allenoates have been
achieved. In the presence of DABCO combined with Et3N, 2-substituted buta-2,3
dienoates reacted with oxime chlorides to afford spirobiisoxazolines in 55-90%
yields via the double 1,3-dipolar cycloaddition. Notably, the construction of
double isoxazoline moieties and two chiral centers including a spiro carbon
center was achieved.
PMID- 29345712
TI - The thiolation of pentafluorobenzene with disulfides by C-H, C-F bond activation
and C-S bond formation.
AB - A metal-free thiolation reaction between pentafluorobenzene and disulfides by C
H, C-F bond activation and C-S bond formation is reported. Bisthiolated
tetrafluorobenzene derivatives would be prepared in moderate to good yields from
pentafluorobenzene and disulfides under mild conditions. A possible mechanism for
the reaction was given.
PMID- 29345713
TI - Synthetic and immunological studies on trimeric MUC1 immunodominant motif antigen
based anti-cancer vaccine candidates.
AB - Therapeutic vaccines have been regarded as a very promising treatment modality
against cancer. Tumor-associated MUC1 is a promising antigen for the design of
antitumor vaccines. However, body's immune tolerance and low immunogenicity of
MUC1 glycopeptides limited their use as effective antigen epitopes of therapeutic
vaccines. To solve this problem, we chose the immune dominant region of MUC1
VNTRs. We designed and synthesized its linear trivalent glycopeptide fragments
and coupled the fragments with BSA. Immunological evaluation indicated that the
antibodies induced by glycosylated MUC1 based vaccine 11 had a stronger binding
than non-glycosylated 10. The novel constructed antigen epitopes have the
potential to overcome the weak immunogenicity of natural MUC1 glycopeptides and
deserve further research.
PMID- 29345714
TI - From discrete to continuous description of spherical surface charge
distributions.
AB - The importance of electrostatic interactions in soft matter and biological
systems can often be traced to non-uniform charge effects, which are commonly
described using a multipole expansion of the corresponding charge distribution.
The standard approach when extracting the charge distribution of a given system
is to treat the constituent charges as points. This can, however, lead to an
overestimation of multipole moments of high order, such as dipole, quadrupole,
and higher moments. Focusing on distributions of charges located on a spherical
surface - characteristic of numerous biological macromolecules, such as globular
proteins and viral capsids, as well as of inverse patchy colloids - we develop a
novel way of representing spherical surface charge distributions based on the von
Mises-Fisher distribution. This approach takes into account the finite spatial
extension of individual charges, and leads to a simple yet powerful way of
describing surface charge distributions and their multipole expansions. In this
manner, we analyze charge distributions and the derived multipole moments of a
number of different spherical configurations of identical charges with various
degrees of symmetry. We show how the number of charges, their size, and the
geometry of their configuration influence the behavior and relative importance of
multipole magnitudes of different order. Importantly, we clearly demonstrate how
neglecting the effect of charge size leads to an overestimation of high-order
multipoles. The results of our work can be applied to construct analytical models
of electrostatic interactions and multipole expansion of charged particles in
diverse soft matter and biological systems.
PMID- 29345715
TI - Tendon - function-related structure, simple healing process and mysterious
ageing.
AB - Tendons are connective tissue structures of paramount importance to human ability
of locomotion. The understanding of their physiology and pathology is gaining
importance as advances in regenerative medicine are being made today. So far,
very few studies were conducted to extend the knowledge about pathology, healing
response and management of tendon lesions. In this paper we summarise actual
knowledge on structure, process of healing and ageing of the tendons. The
structure of tendon is optimised for the best performance of the tissue. Despite
the simplicity of the healing response, numerous studies showed that the problems
with full recovery are common and much more significant than we thought; that is
why we discussed the issue of immobilisation and mechanical stimulation during
healing process. The phenomenon of tendons' ageing is poorly understood. Although
it seems to be a natural and painless process, it is completely different from
degeneration in tendinopathy. Recent studies of biological treatment reported
faster and optimal healing of the tendons when augmented by growth factors and
stem cells. Despite advances in biology of tendons, management of their injuries
is still a challenge for physicians; therefore, further studies are required to
improve treatment outcomes.
PMID- 29345716
TI - Endodontium - together or separately?
AB - Endodontium, otherwise referred to as pulp-dentin complex or endodont. This term
includes two tooth tissues: dentin and pulp, which constitute a structural and
functional unity. These tissues have a huge, inseparable influence on each other
the pulp (inter alia) nourishes the dentine, while the dentin forms a protective
barrier for the pulp. They develop from the papillary tissue (Latin:
papilladentis) from mesenchymal tissue. Nevertheless, in clinical practice this
structural-functional complex is often treated as two separate tissues, and not
as a whole. Adequate knowledge of the structure, function and protective
mechanisms of the endodontium produces successful results in the treatment. The
appropriate choice and application of the therapeutic methods and materials to
the dentin secures vitality of both tissues of this complex.
PMID- 29345717
TI - Vasoconstrictive responses of the cephalic vein during first-time cardiac
implantable electronic device placement.
AB - BACKGROUND: During cardiac implantable electronic device (CIED) implantation
procedures cardiac leads have been mostly introduced transvenously. The
associated injury to the selected vessel and adjacent tissues may induce reflex
vasoconstriction. The aim of the study was to assess the incidence of cephalic
vein (CV) vasoconstriction during first-time CIED implantation. MATERIALS AND
METHODS: Of the 146 evaluated first-time CIED implantation procedures conducted
in our centre in 2016, we selected those during which CV vasoconstriction was
recorded. We focused on the stage of the procedure involving CV cutdown and/or
axillary vein (AV)/subclavian vein (SV) puncture for lead insertion. Only cases
documented via venography were considered. RESULTS: Vasoconstriction was observed
in 11 patients (5 females and 6 males, mean age 59.0 +/- 21.2 years). The
presence of this phenomenon affected the stage of CIED implantation involving
cardiac lead insertion to the venous system, in severe cases, requiring a change
of approach from CV cutdown to AV/SV puncture. The extent of vasoconstriction
front propagation was limited to the nearest valves. Histological examinations of
collected CV samples revealed an altered spatial arrangement of myocytes in the
tunica media at the level of leaflet attachment. CONCLUSIONS: Cephalic vein
vasoconstriction is a rare phenomenon associated with accessing the venous system
during first-time CIED implantation. The propagation of CV constriction was
limited by the location of the nearest valves.
PMID- 29345718
TI - Evaluation of the morphological characteristic and sex differences of sternum by
multi-detector computed tomography.
AB - BACKGROUND: Sternum is one of the skeleton parts which have frequently congenital
anomalies and variations are commonly used by researchers in determining sex. We
evaluated the morphological characteristics and sex-related changes of the
sternum in adult individuals using multidetector computed tomography in our
study. MATERIALS AND METHODS: Two hundred adults (103 female and 97 male) aged
between 18 and 87 years were evaluated. Utilising the morphological
characteristics of the sternum based on the multislice images; length, width and
the thickness of manubrium, length, width and the thickness of corpus sterni,
total length of sternum, sternal angle, sternal index (SI), length of the xiphoid
process, the thickness of xiphoid process, the number of indents of xiphoid
process were measured and a total of 20 parameters were evaluated by adding age,
height and weight to these variables. RESULTS: The mean length of the manubrium,
the length of corpus sterni, the length of total sternum, SI, sternal angle were
found in females 46.7 +/- 5.1, 86.6 +/- 9.7, 133.1 +/- 1.1, 54.47 +/- 10.0 and
163.75 +/- 5.79; in males 51.2 +/- 6,102.4 +/- 13.3, 154.1 +/- 13.1, 50.11 +/-
10.02 and 162.21 +/- 6.17, respectively. We found that Hyrtl's Law and SI did not
provide adequate accuracy for sex determination in our patients. It has been
detected that the length of the manubrium alone is not helpful for individual
samples. Total length of the sternum was found to be more reliable than the
length of the manubrium and the length of corpus sterni. We determined sternal
cleft and sternal foramen as 0.5% and 3.5%, respectively. CONCLUSIONS: We suggest
that the morphometric standards cannot be universally applied and can demonstrate
individual differences. The standard rules must be implemented for every
population.
PMID- 29345719
TI - An anatomical variant: evaluation of accessory canals of the canalis sinuosus
using cone beam computed tomography.
AB - BACKGROUND: The anatomical variation of the anterior superior alveolar nerve
described as canalis sinuosus (CS) is a less known structure of anterior maxilla.
Due to the fact that it contains anterior superior alveolar nerve as well as
veins and arteries, exact localisation of this structure will allow surgeons to
avoid complications. Hence, the aim of this study was to verify the presence,
reveal the frequency and characteristics of accessory canals of CS. MATERIALS AND
METHODS: This study was based on retrospective evaluation of cone beam computed
tomography (CBCT) scans. A total of 1460 CBCT images were analysed and collected
data were noted. The following parameters were recorded: age, sex, presence or
absence of CS, location in relation to the adjacent teeth and impaction of canine
teeth. RESULTS: A total of 6668 accessory canals were found in 1460 CBCT images.
Of these, 672 (46.0%) were from female patients, and 788 (54.0%) were from male
patients. 1034 (70.8%) of 1460 images had at least one accessory canal of CS.
Maxillary intercentral region is the area where accessory canals were seen most
frequently (n = 653, 44.72%). CONCLUSIONS: Canalis sinuosus is a bony canal which
is incidentally found and less known structure of anterior portion of maxilla.
Knowing the accessory canals deriving from this structure will allow surgeons to
avoid complications and non-integration after dental implant procedures.
Conventional imaging modalities have limited value in detecting this
neurovascular structures. Therefore CBCT may have an important role for accurate
diagnosis to reveal anatomical variations.
PMID- 29345720
TI - Effects of nicotine administration in rats on MMP2 and VEGF levels in periodontal
membrane.
AB - BACKGROUND: Nicotine is associated with increased incidence of periodontal
disease and poor response to therapy. This article aimed at identifying the
expression of matrix metalloproteinases 2 (MMPs2) and vascular endothelial growth
factor (VEGF) proteins on extracellular matrix, fibrous distribution and
angiogenetic development in periodontitis caused by nicotine effects on
periodontal membrane. MATERIALS AND METHODS: In this experimental study, rats
were divided into nicotine and control groups. While the rats in the nicotine
group (n = 6) were administered 2 mg/kg nicotine sulphate for 28 days, the
animals in the control group (n = 6) were only administered 1.5 mL physiologic
saline solution subcutaneously for 28 days. RESULTS: Histological sections were
prepared and immunohistochemically stained for MMP2 and VEGF. The sections
stained with Trichrome-Masson were observed under light microscope. VEGF and MMP2
immunoreactivity of periodontal gingiva and dentin was assessed by
immunohistochemical staining. CONCLUSIONS: Nicotine reduces MMP production,
disrupts collagen synthesis and causes periodontitis. We observed that nicotine
increases periodontitis by disrupting periodontal membrane and prevents tooth to
anchor in dental alveoli by disrupting epithelial structure.
PMID- 29345721
TI - Sectioned images and surface models of a cadaver head with reference to botulinum
neurotoxin injection.
AB - BACKGROUND: The aim of this study is to elucidate the anatomical considerations
with reference to botulinum neurotoxin type A (BTX) injection, on sectioned
images and surface models, using Visible Korean. These can be used for medical
education and clinical training in the field of facial surgery. MATERIALS AND
METHODS: Serially sectioned images of the head were obtained from a cadaver.
Significant anatomic structures in the sectioned images were outlined and
assembled to create a surface model. RESULTS: The PDF file (27.8 MB) of the
stacked models can be accessed for free. The file can also be obtained from the
authors by email. Using this file, important anatomical structures associated
with the BTX injection can be investigated in the sectioned images. All surface
models and stereoscopic structures related with the BTX injection are described
in real time. CONCLUSIONS: We hope that these state-of-the-art sectioned images,
outlined images, and surface models will assist students and trainees in
acquiring a better understanding of the anatomy associated with the BTX
injection.
PMID- 29345722
TI - Morphometric properties of the tensor fascia lata muscle in human foetuses.
AB - BACKGROUND: In neonatal and early childhood surgeries such as meningomyelocele
repairs, closing deep wounds and oncological treatment, tensor fasciae lata (TFL)
flaps are used. However, there are not enough data about structural properties of
TFL in foetuses, which can be considered as the closest to neonates in terms of
sampling. This study's main objective is to gather data about morphological
structures of TFL in human foetuses to be used in newborn surgery. MATERIALS AND
METHODS: Fifty formalin-fixed foetuses (24 male, 26 female) with gestational age
ranging from 18 to 30 weeks (mean 22.94 +/- 3.23 weeks) were included in the
study. TFL samples were obtained by bilateral dissection and then surface area,
width and length parameters were recorded. Digital callipers were used for length
and width measurements whereas surface area was calculated using digital image
analysis software. RESULTS: No statistically significant differences were found
in terms of numerical value of parameters between sides and sexes (p > 0.05).
Linear functions for TFL surface area, width, anterior and posterior margin
lengths were calculated as y = -225.652 + 14.417 * age (weeks), y = -5.571 +
0.595 * age (weeks), y = -4.276 + 0.909 * age (weeks), and y = -4.468 + 0.779 *
age (weeks), respectively. CONCLUSIONS: Linear functions for TFL surface area,
width and lengths can be used in designing TFL flap dimensions in newborn
surgery. In addition, using those described linear functions can also be
beneficial in prediction of TFL flap dimensions in autopsy studies.
PMID- 29345723
TI - Anatomical characteristics of the lingual foramen in ancient skulls: a cone beam
computed tomography study in an Anatolian population.
AB - BACKGROUND: The purpose of this study is to evaluate the anatomical features of
lingual foramina and their bony canals in Anatolian ancient mandibles (9-10th
century) by using cone beam computed tomography (CBCT). MATERIALS AND METHODS:
Fifty-eight ancient dry mandibles were scanned with CBCT. Lingual foramina were
grouped into midline, paramedian, posterior foramina and combination of these
groups. Midline group was also classified according to internal surface of the
mandible (gonial tubercles [GTs]). The incidence, vertical distance and diameter
of lingual foramina were measured according to age groups and gender. RESULTS:
The incidence of the lingual foramen was 96.6%. Midline of the symphysis had the
highest incidence (34.4%) of foramina (p < 0.05), followed by both midline and
paramedian type (32.8%; p < 0.05). Classification in terms of GT represented
class 3 as the most encountered group (28.6%). Number of foramina observed in the
mandibles ranged from 0 to 6 with the incidence of 3.4% and 32.8%, respectively.
The male and < 35 years groups presented larger measurement values in midline
region (p < 0.05). CONCLUSIONS: Mandibular lingual foramina and bony canals are
frequently present in ancient mandibles. When compared with modern subjects,
similar findings are observed according to published literatures. CBCT is also
proved to be an effective imaging modality in the detection of lingual foramina
and canals in anthropological studies.
PMID- 29345724
TI - Effects of Cognitive Training on Cognition and Quality of Life of Older Persons
with Dementia.
AB - OBJECTIVES: To evaluate the effect of cognitive training on cognition and health
related quality of life (HRQoL) in community-dwelling persons with dementia.
DESIGN: Single-blind randomized controlled trial with 3- and 9-month follow-up.
SETTING: Adult day care centers in Helsinki, Finland. PARTICIPANTS: Older
individuals with mild to moderate dementia living at home and attending adult day
care twice a week (N = 147; mean age 83, 72% female, 63% at mild stage of
dementia). INTERVENTION: A systematic 12-week training program focused on
subskills of executive function: attention, working memory, cognitive
flexibility, and planning. The intervention group (n = 76) underwent cognitive
training twice a week for 45 minutes, and the control group (n = 71) attended day
care as usual. MEASUREMENTS: Primary outcomes were the Alzheimer's Disease
Assessment Scale-Cognitive subscale (ADAS-Cog) for global cognition and the 15
dimensional instrument (15D) for HRQoL. The outcomes were measured at baseline
and 3 and 9 months. RESULTS: Both groups deteriorated in global cognition and
HRQoL during follow-up, and there were no differences between the two groups in
change on the ADAS-Cog (P = .43) or 15D (P = .61) over time (adjusted for age and
sex). At 3 months, changes were 0.8 (95% confidence interval (CI) = -0.2-1.8) for
the intervention group and 1.7 (95% CI = 0.6-2.7) for the control group on the
ADAS-Cog and -0.040 (95% CI = -0.058 to -0.021) for the intervention group and
0.037 (95% CI = -0.056 to -0.018) for the control group on the 15D. CONCLUSION:
Systematic cognitive training had no effect on global cognition or HRQoL in
community-living persons with mild to moderate dementia.
PMID- 29345726
TI - ?
PMID- 29345725
TI - Polyols and UV-sunscreens in the Prasiola-clade (Trebouxiophyceae, Chlorophyta)
as metabolites for stress response and chemotaxonomy.
AB - In many regions of the world, aeroterrestrial green algae of the Trebouxiophyceae
(Chlorophyta) represent very abundant soil microorganisms, and hence their
taxonomy is crucial to investigate their physiological performance and ecological
importance. Due to a lack in morphological features, taxonomic and phylogenetic
studies of Trebouxiophycean algae can be a challenging task. Since chemotaxonomic
markers could be a great assistance in this regard, 22 strains of aeroterrestrial
Trebouxiophyceae were chemically screened for their polyol-patterns as well as
for mycosporine-like amino acids (MAAs) in their aqueous extracts using RP-HPLC
and LC-MS. d-sorbitol was exclusively detected in members of the Prasiolaceae
family. The novel MAA prasiolin and a related compound ("prasiolin-like") were
present in all investigated members of the Prasiola-clade, but missing in all
other tested Trebouxiophyceae. While prasiolin could only be detected in field
material directly after extraction, the "prasiolin-like" compound present in the
other algae was fully converted into prasiolin after 24 h. These findings suggest
d-sorbitol and prasiolin-like compounds are suitable chemotaxonomic markers for
the Prasiolaceae and Prasiola-clade, respectively. Additional UV-exposure
experiments with selected strains show that MAA formation and accumulation can be
induced, supporting their role as UV-sunscreen.
PMID- 29345727
TI - The Petal Project: An innovation in sexual healthcare and education for Kenyan
schoolgirl.
AB - In the western province of Nyanza in Kenya, girls and women face an issue all too
common in the developing world-little or no access to affordable means to
effectively managing their menstrual flow. As a result, many stay at home or drop
out of school because they are teased and embarrassed. Some approach men for
money to buy pads and are forced, in return, to engage in transactional sex. The
girls may not be able to return to school at all due to pregnancy. The story
literally and figuratively continues to cycle, keeping girls in positions of
dependency and poverty. In May 2011, two visiting nursing faculty conducting
health clinics with students, were approached by a young male school volunteer
who shared his observations and unease with what he saw happening. Concerns
shared that day spawned an initiative known as the Petal Project, which has
yielded thousands of starter kits hand-sewn and delivered to girls in Kenya. The
Petal Project has grown in popularity and participation on their college campus
and in neighboring communities. Since its inception, this initiative has expanded
to include over six countries and has positively impacted the lives of hundreds
of givers and receivers.
PMID- 29345728
TI - Analytical performance of the ThyroSeq v3 genomic classifier for cancer diagnosis
in thyroid nodules.
AB - BACKGROUND: Molecular tests have clinical utility for thyroid nodules with
indeterminate fine-needle aspiration (FNA) cytology, although their performance
requires further improvement. This study evaluated the analytical performance of
the newly created ThyroSeq v3 test. METHODS: ThyroSeq v3 is a DNA- and RNA-based
next-generation sequencing assay that analyzes 112 genes for a variety of genetic
alterations, including point mutations, insertions/deletions, gene fusions, copy
number alterations, and abnormal gene expression, and it uses a genomic
classifier (GC) to separate malignant lesions from benign lesions. It was
validated in 238 tissue samples and 175 FNA samples with known surgical follow
up. Analytical performance studies were conducted. RESULTS: In the training
tissue set of samples, ThyroSeq GC detected more than 100 genetic alterations,
including BRAF, RAS, TERT, and DICER1 mutations, NTRK1/3, BRAF, and RET fusions,
22q loss, and gene expression alterations. GC cutoffs were established to
distinguish cancer from benign nodules with 93.9% sensitivity, 89.4% specificity,
and 92.1% accuracy. This correctly classified most papillary, follicular, and
Hurthle cell lesions, medullary thyroid carcinomas, and parathyroid lesions. In
the FNA validation set, the GC sensitivity was 98.0%, the specificity was 81.8%,
and the accuracy was 90.9%. Analytical accuracy studies demonstrated a minimal
required nucleic acid input of 2.5 ng, a 12% minimal acceptable tumor content,
and reproducible test results under variable stress conditions. CONCLUSIONS: The
ThyroSeq v3 GC analyzes 5 different classes of molecular alterations and provides
high accuracy for detecting all common types of thyroid cancer and parathyroid
lesions. The analytical sensitivity, specificity, and robustness of the test have
been successfully validated and indicate its suitability for clinical use. Cancer
2018;124:1682-90. (c) 2018 American Cancer Society.
PMID- 29345729
TI - Sinus node dysfunction after heart transplantation-An analysis of risk factors
and atrial pacing burden.
AB - INTRODUCTION: We investigated the development of sinus node dysfunction (SND)
requiring pacemaker implantation after heart transplant (HTx) especially
regarding pacing burden in these patients. PATIENTS AND METHODS: Patients
requiring a pacemaker for SND were compared to all other patients in an HTx
cohort including transplant patients from 1981 to 2016. RESULTS: Sinus node
dysfunction requiring pacemaker implantation developed in 118 patients (10%).
These patients had received a biatrial anastomosis more frequently than those in
the No SND group 95.8% vs 90.0% (P = .042). The ratio of reperfusion time to
aortic cross-clamp time was significantly smaller in the SND group compared to
the No SND group 71.7% vs 80.3% (P = .033). This also holds for the ratio of
reperfusion time to ischemia time, which was 23.2% and 28.6%, respectively (P =
.032). Pacing burden decreased from 90.5% to 66.3% after 2 years and remained
around this value in the remaining 4 years of follow-up. CONCLUSION: We
identified the biatrial anastomosis and a low ratio of reperfusion time to aortic
cross-clamp time as well as to ischemia time as risk factors for SND requiring
pacing. After implantation pacemakers continue to pace for over 60% of the time
after 6 years.
PMID- 29345730
TI - Regional pattern of microgliosis in sporadic Creutzfeldt-Jakob disease in
relation to phenotypic variants and disease progression.
AB - AIMS: The aim of this study was to describe the regional profiles of microglial
activation in sporadic Creutzfeldt-Jakob disease (sCJD) subtypes and analyse the
influence of prion strain, disease duration and codon 129 genotype. METHODS: We
studied the amount/severity and distribution of activated microglia, protease
resistant prion protein (PrPSc ) spongiform change, and astrogliosis in eight
regions of 57 brains, representative of the entire spectrum of sCJD subtypes.
RESULTS: In each individual subtype, the regional extent and distribution of
microgliosis significantly correlated with PrPSc deposition and spongiform
change, leading to subtype-specific 'lesion profiles'. However, large differences
in the ratio between PrPSc load or the score of spongiform change and microglial
activation were seen among disease subtypes. Most significantly, atypical sCJD
subtypes such as VV1 and MM2T showed a degree of microglial activation comparable
to other disease variants despite the relatively low PrPSc deposition and the
less severe spongiform change. Moreover, the mean microglial total load was
significantly higher in subtype MM1 than in MM2C, whereas the opposite was true
for the PrPSc and spongiform change total loads. Finally, some sCJD subtypes
showed distinctive regional cerebellar profiles of microgliosis characterized by
a high granular/molecular layer ratio (MV2K) and/or a predominant involvement of
white matter (MVK and MM2T). CONCLUSIONS: Microglial activation is an early event
in sCJD pathogenesis and is strongly influenced by prion strain, PRNP codon 129
genotype and disease duration. Microglial lesion profiling, by highlighting
strain-specific properties of prions, contributes to prion strain
characterization and classification of human prion diseases, and represents a
valid support to molecular and histopathologic typing.
PMID- 29345731
TI - Student evaluations of teaching (SET): Guidelines for their use.
AB - Student evaluations of teaching (SET) provide a structured way of collecting
feedback from students about the course and teacher's effectiveness. We reviewed
literature describing use of SET across a broad range of disciplines in
undergraduate and graduate education to provide guidelines for faculty in using
SET in a nursing or other health professions program. On SET tools, students
typically rate their satisfaction with a course and perceptions about the quality
of the teaching. It is important to evaluate SET tools prior to their use
including pilot testing tools with students because studies show students may not
interpret items or questions on a SET tool as faculty intended. Common uses of
the evaluation data from SET include improvement of courses and teaching, and for
personnel decisions.
PMID- 29345732
TI - Near Visual Impairment Incidence in Relation to Diabetes in Older People: The
Three-Cities Study.
AB - OBJECTIVES: To characterize the relationship between diabetes mellitus (DM) and
future risk of near vision impairment (VI) in a community-dwelling population of
older people. DESIGN: Seven-year population-based longitudinal study. SETTING:
Three-Cities Study, a French prospective study designed to assess the risk of
cognitive and functional decline attributable to vascular factors. PARTICIPANTS:
Community-dwelling individuals aged 65 and older (N = 8,412). MEASUREMENTS: DM
was determined at baseline according to self-reported DM, antidiabetic treatment,
and fasting blood glucose. Near visual acuity was measured at baseline and 2, 4,
and 7 years later. Near VI was defined as a Snellen score greater than 20/30.
RESULTS: DM was associated with a higher risk of near VI in an adjusted model
(hazard ratio (HR) = 1.24, 95% confidence interval (CI) = 1.02-1.52, P = .03).
Because of an interaction between Body Mass Index (BMI) and diagnosed DM, the
longitudinal analyses were stratified according to BMI category. DM was
associated with greater risk of near VI only in underweight (BMI <21.0 kg/m2 , HR
= 2.89, 95% CI = 1.18-7.03) and normal-weight (BMI 21.0-24.9 kg/m2 , HR = 1.60,
95% CI = 1.10-2.32), but not overweight (P = .69) and obese (P = .09) subjects.
CONCLUSION: DM is a risk factor for near VI in older people, particularly in
those with a low or normal BMI. This risk profile should be taken into account in
older adults to support their independence.
PMID- 29345733
TI - Putative mechanisms of cognitive decline with implications for clinical research
and practice.
AB - Multiple intrinsic and extrinsic mechanisms contribute to vulnerability of
cognitive decline and nurses play a significant role in assisting individuals and
families to use strategies for healthy cognitive aging. The objective of this
narrative review is to provide a synthesis of the intrinsic and extrinsic
mechanisms of cognitive decline and conditions that are associated with cognitive
decline. Well-established intrinsic mechanisms of cognitive decline include
aging, apolipoprotein E (APOE) epsilon4 carrier status, SORL1 mutations,
neuroinflammation, mitochondrial dysfunction, amyloid deposition, and
demyelination. Extrinsic risk factors include obesity, diabetes, hypertension,
elevated lipid panel, metabolic syndrome, depression, traumatic brain injury,
substance use, heart failure, and stroke. The various definitions of cognitive
decline as well as the intrinsic and extrinsic factors that impact cognition as
humans age should be incorporated in future clinical research studies. Nurses may
use this information to help patients make lifestyle choices regarding cognitive
health.
PMID- 29345734
TI - Glove port path for transanal resection of rectal lesion - a video vignette.
PMID- 29345735
TI - Landscape simplification reduces classical biological control and crop yield.
AB - Agricultural intensification resulting in the simplification of agricultural
landscapes is known to negatively impact the delivery of key ecosystem services
such as the biological control of crop pests. Both conservation and classical
biological control may be influenced by the landscape context in which they are
deployed; yet studies examining the role of landscape structure in the
establishment and success of introduced natural enemies and their interactions
with native communities are lacking. In this study, we investigated the
relationship between landscape simplification, classical and conservation
biological control services and importantly, the outcome of these interactions
for crop yield. We showed that agricultural simplification at the landscape scale
is associated with an overall reduction in parasitism rates of crop pests.
Additionally, only introduced parasitoids were identified, and no native
parasitoids were found in crop habitat, irrespective of agricultural landscape
simplification. Pest densities in the crop were lower in landscapes with greater
proportions of semi-natural habitats. Furthermore, farms with less semi-natural
cover in the landscape and consequently, higher pest numbers, had lower yields
than farms in less agriculturally dominated landscapes. Our study demonstrates
the importance of landscape scale agricultural simplification in mediating the
success of biological control programs and highlights the potential risks to
native natural enemies in classical biological control programs against native
insects. Our results represent an important contribution to an understanding of
the landscape-mediated impacts on crop yield that will be essential to
implementing effective policies that simultaneously conserve biodiversity and
ecosystem services.
PMID- 29345736
TI - Palbociclib in combination with letrozole as first-line treatment for advanced
breast cancer: A Japanese phase II study.
AB - This single-arm, open-label, phase II study in 42 Japanese postmenopausal
patients with estrogen receptor-positive/human epidermal growth factor receptor 2
negative (ER+/HER2-) advanced breast cancer evaluated the efficacy, safety, and
pharmacokinetics of first-line palbociclib (125 mg once daily, 3 weeks on/1 week
off) coadministered with letrozole (2.5 mg once daily). Primary endpoint of
investigator-assessed 1-year progression-free survival (PFS) probability was
75.0% (90% CI, 61.3%-84.4%), far surpassing the 40% lower limit of the 90% CI
supporting efficacy. Median duration of treatment was 438 days. Among secondary
efficacy measures, median PFS was not reached (95% CI, 16.7: not estimable),
17/42 patients (40.5%) had an objective response, 36/42 (85.7%) maintained
disease control, and 27/42 (64.3%) remained in follow-up. Median overall survival
was not reached, and 1-year survival probability was 92.9% (95% CI, 79.5%-97.6%).
Results of intensive pharmacokinetics in a subset of 6 patients showed
palbociclib steady-state mean area under the plasma concentration-time curve over
the dosing interval [tau] and mean maximum plasma concentration were 1979 ng.h/mL
and 124.7 ng/mL, respectively. For day 15 plasma samples from cycles 1 and 2,
geometric mean of the within-patient mean trough concentration was 90.1 ng/mL.
The most common treatment-related adverse events were neutropenia (100%) and
stomatitis (73.8%). There was 1 case of treatment-related febrile neutropenia.
Toxicities were generally tolerated and manageable by dose modifications and/or
medical care. Efficacy and safety of first-line palbociclib plus letrozole
therapy is supported in Japanese postmenopausal patients with treatment-naive
ER+/HER2- advanced breast cancer.
PMID- 29345738
TI - Elucidation of the Oxygen Reduction Volcano in Alkaline Media using a Copper
Platinum(111) Alloy.
AB - The relationship between the binding of the reaction intermediates and oxygen
reduction activity in alkaline media was experimentally explored. By introducing
Cu into the 2nd surface layer of a Pt(111) single crystal, the surface reactivity
was tuned. In both 0.1 m NaOH and 0.1 m KOH, the optimal catalyst should exhibit
OH binding circa 0.1 eV weaker than Pt(111), via a Sabatier volcano; this
observation suggests that the reaction is mediated via the same surface bound
intermediates as in acid, in contrast to previous reports. In 0.1 m KOH, the
alloy catalyst at the peak of the volcano exhibits a maximum activity of 101+/-8
mA cm-2 at 0.9 V vs. a reversible hydrogen electrode (RHE). This activity
constitutes a circa 60-fold increase over Pt(111) in 0.1 m HClO4 .
PMID- 29345739
TI - Exact Mapping from Many-Spin Hamiltonians to Giant-Spin Hamiltonians.
AB - Thermodynamic and spectroscopic data of exchange-coupled molecular spin clusters
(e.g. single-molecule magnets) are routinely interpreted in terms of two
different models: the many-spin Hamiltonian (MSH) explicitly considers couplings
between individual spin centers, while the giant-spin Hamiltonian (GSH) treats
the system as a single collective spin. When isotropic exchange coupling is weak,
the physical compatibility between both spin Hamiltonian models becomes a serious
concern, due to mixing of spin multiplets by local zero-field splitting (ZFS)
interactions ('S-mixing'). Until now, this effect, which makes the mapping MSH
>GSH ('spin projection') non-trivial, had only been treated perturbationally (up
to third order), with obvious limitations. Here, based on exact diagonalization
of the MSH, canonical effective Hamiltonian theory is applied to construct a GSH
that exactly matches the energies of the relevant (2S+1) states comprising an
effective spin multiplet. For comparison, a recently developed strategy for the
unique derivation of effective ('pseudospin') Hamiltonians, now routinely
employed in ab initio calculations of mononuclear systems, is adapted to the
problem of spin projection. Expansion of the zero-field Hamiltonian and the
magnetic moment in terms of irreducible tensor operators (or Stevens operators)
yields terms of all ranks k (up to k=2S) in the effective spin. Calculations
employing published MSH parameters illustrate exact spin projection for the well
investigated [Ni(hmp)(dmb)Cl]4 ('Ni4 ') single-molecule magnet, which displays
weak isotropic exchange (dmb=3,3-dimethyl-1-butanol, hmp- is the anion of 2
hydroxymethylpyridine). The performance of the resulting GSH in finite field is
assessed in terms of EPR resonances and diabolical points. The large tunnel
splitting in the M=+/- 4 ground doublet of the S=4 multiplet, responsible for
fast tunneling in Ni4 , is attributed to a Stevens operator with eightfold
rotational symmetry, marking the first quantification of a k=8 term in a spin
cluster. The unique and exact mapping MSH->GSH should be of general importance
for weakly-coupled systems; it represents a mandatory ultimate step for comparing
theoretical predictions (e.g. from quantum-chemical calculations) to ZFS,
hyperfine or g-tensors from spectral fittings.
PMID- 29345737
TI - Present status and future perspective of peptide-based vaccine therapy for
urological cancer.
AB - Use of peptide-based vaccines as therapeutics aims to elicit immune responses
through antigenic epitopes derived from tumor antigens. Peptide-based vaccines
are easily synthesized and lack significant side-effects when given in vivo.
Peptide-based vaccine therapy against several cancers including urological
cancers has made progress for several decades, but there is no worldwide approved
peptide vaccine. Peptide vaccines were also shown to induce a high frequency of
immune response in patients accompanied by clinical efficacy. These data are
discussed in light of the recent progression of immunotherapy caused by the
addition of immune checkpoint inhibitors thus providing a general picture of the
potential therapeutic efficacy of peptide-based vaccines and their combination
with other biological agents. In this review, we discuss the mechanism of the
antitumor effect of peptide-based vaccine therapy, development of our peptide
vaccine, recent clinical trials using peptide vaccines for urological cancers,
and perspectives of peptide-based vaccine therapy.
PMID- 29345740
TI - Accurate Etiological Diagnosis of Dementia Contributes to Better Clinical Care.
PMID- 29345741
TI - Geriatric Syndromes, Dementia Subtypes, Gizmo Idolatry.
PMID- 29345742
TI - Cognitive Training for Older Adults: What Works?
PMID- 29345743
TI - Refining mortality estimates in shark demographic analyses: a Bayesian inverse
matrix approach.
AB - Leslie matrix models are an important analysis tool in conservation biology that
are applied to a diversity of taxa. The standard approach estimates the finite
rate of population growth (lambda) from a set of vital rates. In some instances,
an estimate of lambda is available, but the vital rates are poorly understood and
can be solved for using an inverse matrix approach. However, these approaches are
rarely attempted due to prerequisites of information on the structure of age or
stage classes. This study addressed this issue by using a combination of Monte
Carlo simulations and the sample-importance-resampling (SIR) algorithm to solve
the inverse matrix problem without data on population structure. This approach
was applied to the grey reef shark (Carcharhinus amblyrhynchos) from the Great
Barrier Reef (GBR) in Australia to determine the demography of this population.
Additionally, these outputs were applied to another heavily fished population
from Papua New Guinea (PNG) that requires estimates of lambda for fisheries
management. The SIR analysis determined that natural mortality (M) and total
mortality (Z) based on indirect methods have previously been overestimated for C.
amblyrhynchos, leading to an underestimated lambda. Updated distributions of Z
and lambda were produced for the GBR population and corrected obvious error in
the demographic parameters for the PNG population. This approach provides
opportunity for the inverse matrix approach to be applied more broadly to
situations where information on population structure is lacking.
PMID- 29345744
TI - Land surveys show regional variability of historical fire regimes and dry forest
structure of the western United States.
AB - An understanding of how historical fire and structure in dry forests (ponderosa
pine, dry mixed conifer) varied across the western United States remains
incomplete. Yet, fire strongly affects ecosystem services, and forest restoration
programs are underway. We used General Land Office survey reconstructions from
the late 1800s across 11 landscapes covering ~1.9 million ha in four states to
analyze spatial variation in fire regimes and forest structure. We first
synthesized the state of validation of our methods using 20 modern validations,
53 historical cross-validations, and corroborating evidence. These show our
method creates accurate reconstructions with low errors. One independent modern
test reported high error, but did not replicate our method and made many
calculation errors. Using reconstructed parameters of historical fire regimes and
forest structure from our validated methods, forests were found to be non-uniform
across the 11 landscapes, but grouped together in three geographical areas. Each
had a mixture of fire severities, but dominated by low-severity fire and low
median tree density in Arizona, mixed-severity fire and intermediate to high
median tree density in Oregon-California, and high-severity fire and intermediate
median tree density in Colorado. Programs to restore fire and forest structure
could benefit from regional frameworks, rather than one size fits all.
PMID- 29345745
TI - Comparison of Flow Cytometric Methods for the Enumeration of Residual Leucocytes
in Leucoreduced Blood Products: A Multicenter Study.
AB - The BD FACSViaTM System features novel designs in hardware, software, and
instrument QC. We compared the performance of the BD FACSVia System using the BD
LeucocountTM kit with the BD FACSCaliburTM flow cytometer. Leucoreduced platelet
(PLT, n = 252) and red blood cell (RBC, n = 278) specimens were enrolled at four
sites. Each specimen was stained in four tubes using the BD Leucocount kit
reagents and acquired on the two systems. BD Leucocount Control cells (high and
low) were used to evaluate the inter-site reproducibility on the BD FACSVia
System at three sites over 20 days. Deming regression and Bland-Altman analysis
were performed to determine the WBC absolute counts on the BD FACSVia System vs.
the BD FACSCalibur system. Assay accuracy for the range of 0-350 WBCs/ul was
adequate. For samples with <25 WBCs/ul, the bias with 95% limits of agreement was
0.136 (-1.897 to 2.169) WBC/ul for PLTs (n = 184) and 0.170 (-2.025 to 2.365)
WBC/ul for RBCs (n = 193). For inter-site reproducibility, the CV% was 6.46%
(upper 95% CI 7.16%) for the PLT high control and 9.49% (10.52%) for the PLT low
control. The CV% was 7.51% (8.32%) for the RBC high control and 10.76% (11.92%)
for the RBC low control. The BD FACSVia System reported equivalent results of WBC
absolute counts for leucoreduced PLT and RBC samples compared to the BD
FACSCalibur system. The inter-laboratory reproducibility of the BD FACSVia System
met study specifications. (c) 2018 The Authors. Cytometry Part A Published by
Wiley Periodicals, Inc. on behalf of ISAC.
PMID- 29345747
TI - Recurrent IgA nephropathy after renal transplantation and steroid withdrawal.
AB - Immunoglobulin A nephropathy (IgAN) is the most common primary
glomerulonephritis; the reported recurrence rate of IgAN after renal
transplantation is as high as 13%-50%. The impact of immunosuppressive therapy
and steroid withdrawal on the risk of recurrence of IgAN is still under debate.
We performed a retrospective single-center study, selecting 123 kidney
transplants (rtx) in 120 patients, between January 1995 and December 2012, with
IgAN on the native kidney. In 51 of 123 transplants, at least one post
transplantation biopsy for clinical indication was performed; in 28 of 51
transplants, IgAN recurrence (IgANr) was demonstrated. This group (G1; N = 28)
was compared with a group without IgANr (G2; N = 23). In our study, clinically
evident IgANr rate was 54.9% (28/51) on biopsied patients. At discharge, the use
of the immunosuppressant drugs (tacrolimus, cyclosporine A, mycophenolate
mofetil, azathioprine, mTor inhibitors) was not associated with an increased risk
of IgANr (P = NS). At discharge, all patients were steroid treated. Neither the
use of tacrolimus, mycophenolate mofetil, nor mTor inhibitors (mTori) at biopsy
time were associated with IgANr. However, IgANr was significantly higher in
patients who experienced steroid withdrawal at any post-transplantation time (OR
7.7 P = .03). The median time to recurrence after steroid withdrawal was 59
months (min 4.18, max 113.2).
PMID- 29345748
TI - Kudingcha and Fuzhuan Brick Tea Prevent Obesity and Modulate Gut Microbiota in
High-Fat Diet Fed Mice.
AB - SCOPE: Kudingcha (KDC) from Ilex kudingcha and Fuzhuan brick tea (FBT) are
popular beverages in China, and their preventive and therapeutic roles in
metabolic disorders have been reported. However, the relationship between the gut
microbiota modulatory effects of KDC and FBT and prevention of obesity is still
not clearly understood. METHODS AND RESULTS: KDC and FBT are tested individually
for their capacities to prevent obesity and modulate the gut microbiota in high
fat diet (HFD) fed C57BL/6J mice. The results show that both KDC and FBT
supplementation could modulate oxidative injury, inflammation, lipid metabolism,
and reduce HFD induced obesity significantly. Both KDC and FBT could enhance the
diversity of gut microbiota. KDC could reduce the relative abundance of
Erysipelotrichaceae, while FBT could reduce the ratio of Firmicutes to
Bacteroidetes and enhance the relative abundance of Bifidobacteriaceae.
CONCLUSION: These findings suggest that KDC and FBT could attenuate features of
the metabolic syndrome in HFD-fed mice, which might be due to the modulation of
gut microbiota by KDC and FBT.
PMID- 29345746
TI - History of genome editing in yeast.
AB - For thousands of years humans have used the budding yeast Saccharomyces
cerevisiae for the production of bread and alcohol; however, in the last 30-40
years our understanding of the yeast biology has dramatically increased, enabling
us to modify its genome. Although S. cerevisiae has been the main focus of many
research groups, other non-conventional yeasts have also been studied and
exploited for biotechnological purposes. Our experiments and knowledge have
evolved from recombination to high-throughput PCR-based transformations to highly
accurate CRISPR methods in order to alter yeast traits for either research or
industrial purposes. Since the release of the genome sequence of S. cerevisiae in
1996, the precise and targeted genome editing has increased significantly. In
this 'Budding topic' we discuss the significant developments of genome editing in
yeast, mainly focusing on Cre-loxP mediated recombination, delitto perfetto and
CRISPR/Cas.
PMID- 29345749
TI - Self-production of oxygen system CaO2 /MnO2 @PDA-MB for the photodynamic therapy
research and switch-control tumor cell imaging.
AB - Photodynamic therapy (PDT) holds promise in biochemical study and tumor
treatment. A novel multifunctional nanosystem CaO2 /MnO2 @polydopamine (PDA)
methylene blue (MB) nanosheet (CMP-MB) was designed. CaO2 nanoparticles were
encapsulated by MnO2 nanosheet, and then PDA was coated on the surface of CaO2
/MnO2 nanosheets, which could adsorb photosensitizer MB through hydrophobic
interaction or pi-pi stacking. In this nanosystem, CaO2 /MnO2 had the ability of
self-production of oxygen, which solved the problem of tumor hypoxia largely.
Moreover, it is worth mentioning that the fluorescence of MB was suppressed by
MnO2 , while its emission was triggered in the simulated tumor microenvironment.
Therefore, CMP-MB nanosheet could be used to switch-control cell imaging
potentially. 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide
testing and Live/Dead assay confirmed CMP-MB nanosheet had fewer side effects
without illumination while it destroyed Hela cell with the illumination of light.
Vitro cell experiment demonstrated CMP-MB nanosheet could achieve tumor
microenvironment responsive imaging and inhibit tumor cell growth under
illumination effectively. Therefore, the system has great potential for PDT
application and switch-control tumor cell imaging. (c) 2018 Wiley Periodicals,
Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2544-2552, 2018.
PMID- 29345750
TI - Mobility Trajectories at the End of Life: Comparing Clinical Condition and Latent
Class Approaches.
AB - OBJECTIVES: To assess mobility disability trajectories before death in a large
sample of very old adults using two analytical approaches to determine how well
they corresponded. DESIGN: Decedent sample from the Health, Aging and Body
Composition (Health ABC) Study. Data were collected between 1997 and 2015.
SETTING: Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS:
Individuals randomly selected from well-functioning white Medicare beneficiaries
and all black community residents meeting age criteria (70-79) (N = 3,075).
MEASUREMENTS: Participants were interviewed in person or by phone at least every
six months throughout the study. Of the 1,991 participants who died by the end of
the study, 1,410 had been interviewed for 3 years before death, including an
interview 6 months before dying. We analyzed self-reported mobility collected
prospectively at 6-month intervals during the last 3 years of life. We derived
trajectories in two ways: by averaging decline within decedent groups
prespecified according to clinical conditions and by estimating trajectory models
using maximum-likelihood semiparametric modeling. RESULTS: Ninety-eight percent
of decedents were classified according to 4 prespecified clinical conditions
(sudden death, terminal, organ failure, frailty), which produced groups with
different characteristics. Five disability trajectories were identified: late
decline, progressive disability, moderate disability, early decline, and
persistent disability. Disability trajectory and clinical condition grouping
confirmed previous research but were only marginally related. CONCLUSION: Derived
disability trajectories and grouping according to clinical condition provide
useful information about different facets of the end-of-life experience. The lack
of fit between them suggests a need for greater attention to heterogeneity in
disability in the period before death.
PMID- 29345751
TI - First evidence of freezing tolerance in a resurrection plant: insights into
molecular mobility and zeaxanthin synthesis in the dark.
PMID- 29345752
TI - Oxidative Mechanochemistry: Direct, Room-Temperature, Solvent-Free Conversion of
Palladium and Gold Metals into Soluble Salts and Coordination Complexes.
AB - Noble metals are valued, critical elements whose chemical activation or recycling
is challenging, and traditionally requires high temperatures, strong acids or
bases, or aggressive complexation agents. By using elementary palladium and gold,
demonstrated here is the use of mechanochemistry for noble-metal activation and
recycling by mild, clean, solvent-free, and room-temperature chemistry. The
process leads to direct, efficient, one-pot conversion of the metals, including
spent catalysts, into either simple water-soluble salts or metal-organic
catalysts.
PMID- 29345753
TI - Restorative proctocolectomy and ileal pouch-anal anastomosis for right-sided
colonic adenocarcinoma in familial adenomatous polyposis: an abdominal
laparoscopic approach combined with transanal total mesorectal excision - a video
vignette.
PMID- 29345754
TI - Long-term follow-up after full-split liver transplantation and its applicability
in the recent transplant era.
AB - INTRODUCTION: Full-split liver transplantation (LTX) offers the possibility to
expand the donor pool by utilization of one liver for two adults. The aim of our
study was to analyze the long-term outcome in a large series and its
applicability in the recent transplant era. METHODS: We performed a retrospective
analysis of all full-split LTX from deceased donors (1999-2015). Additionally,
the potential of full-split LTX was retrospectively analyzed in all whole organ
LTX recipients between 2006 and 2015 (after introduction of the MELD allocation).
RESULTS: We performed 44 full-split LTX, thereof 82% before introduction of the
MELD-based allocation system in Germany. Analysis showed highly selected
recipients (median MELD score 8 points) and organ data (median donor age 30
years). 5- and 10-year patient survival rates after full-left and full-right LTX
were 90.7%/90.7% and 85.2%/56.8% (P = .301), corresponding graft survival rates
were 80.5%/80.5% in full-left grafts and 73.7%/36.8% in full-right graft (P =
.198). CONCLUSION: In the past, in case of strict donor and recipient selection,
full-split LTX was a feasible method with a good outcome. Due to introduction of
the national waiting list with a patient-oriented allocation based on the MELD
score in 2006, full-split LTX seems to be not any longer applicable.
PMID- 29345755
TI - Expression of hepatic progenitor cell markers in acute cellular rejection of
liver allografts-An immunohistochemical study.
AB - BACKGROUND: Hepatic progenitor cells (HPC) are induced following liver injury to
facilitate regeneration. Acute cellular rejection (ACR) is a common complication
after liver transplantation as a result of immune-mediated liver injury. In this
study, we characterized HPC phenotype in liver allograft biopsy with ACR. We also
explored the correlation between expression HPC immunophenotype and
clinicopathological parameters. METHODS: Forty-four liver allograft biopsies
performed between 2008 and 2016 in a single center with histologically proven ACR
were examined for immunohistochemical expression of HPC markers CK19 and Sox9.
The number of positive-staining cells was assessed and correlated with
clinicopathological features by statistical analysis. RESULTS: HPC phenotype
expression as denoted by CK19 and Sox9 staining was detected in the liver tissue
with ACR. The numbers of CK19+ and Sox9+ cells were positively correlated. A
larger number of CK19+ cells were associated with higher serum aspartate
aminotransferase (AST) level at biopsy. By histological rejection score, a larger
number of Sox9+ cells were associated with a higher score of bile duct damage.
CONCLUSION: Expression HPC markers were correlated with clinical and histological
parameters in ACR. Expression of each individual marker may be more tightly
associated with a particular component of the ACR process.
PMID- 29345756
TI - Clinical Intentions of Antibiotics Prescribed Upon Discharge to Hospice Care.
AB - OBJECTIVES: To better understand the clinical intentions for antibiotic
prescribing upon discharge from acute care to hospice care. DESIGN: Retrospective
cohort study. SETTING: Five hundred forty-four-bed academic, acute-care, tertiary
referral hospital in Portland, Oregon. PARTICIPANTS: Adults (>=18) who received
an outpatient prescription for antibiotics on discharge from an acute care
hospital to hospice care between January 1, 2009 and December 31, 2011 (N = 149).
MEASUREMENTS: We determined whether antibiotics were indicated for treatment of
an active infection, palliative treatment, prophylaxis, or prescribed according
to family or participant preference. RESULTS: Antibiotics were prescribed to
17.6% (n = 149) of individuals discharged to hospice care over the 3-year study
period. Antibiotics were most frequently prescribed for pneumonia (19.5%),
urinary tract infections (18.9%), and gastrointestinal tract infections (17.0%).
The explicit rationale for antibiotic prescription was documented for only 72
prescriptions (45.3%). For 84 (52.8%) participants, antibiotics were used to
treat an active infection in the hospital. Of prescriptions with a documented
rationale, 37.5% indicated that the intent was curative, 26.4% prophylaxis, and
22.2% to suppress an infection. For 19.4% of prescriptions, participants or their
family members specifically wanted to be treated with antibiotics. Only 9.7% of
prescriptions specifically indicated that antibiotics were prescribed for
palliative reasons. CONCLUSION: Antibiotics were frequently prescribed for
treatment of active infection in individuals discharged to hospice care. Further
research is needed to document antibiotic benefits and risks and optimize
medication management at the end of life.
PMID- 29345758
TI - Continuous deacetylation of cephalosporins.
AB - Continuous deacetylation of cephalosporin C, 7-aminocephalosporanic acid, and of
2-methoxyethyl acetate in packed beds of an immobilized esterase is described by
simple empirical equations relating conversion to space velocity and temperature.
The choice of process conditions is discussed in relation to the effects of
temperature on column efficiency, column life, growth of microbial contaminants,
and the rates of thermal decomposition of the substrates. At the preferred
temperature of 10 degrees C columns were operated continuously for one month with
only small losses in efficiency.
PMID- 29345759
TI - Continuous conversion of sucrose to fructose and gluconic acid by immobilized
yeast cell multienzyme complex.
AB - A multienzyme complex consisting of invertase, glucose oxidase, and catalase was
reconstituted by binding glucose oxidase using concanavalin A (Con A) to the cell
wall of Sacchararomyces cerevisiae, previously induced for maximal activities of
invertase and catalase. The cell flocculate obtained was stabilized by entrapment
in polyacrylamide using gamma irradiation at 100 kR. This complex showed a
shortening of the lag period and enhancement in gluconic acid production as
compared to a similar mixture of soluble enzymes. The efficacy of the multienzyme
complex has been compared with that of mixed multienzyme system composed of
individually immobilized enzymes. The immobilized multienzyme complex in a
continuous-flow stirred-tank reactor system could be operated for continuous
conversion of sucrose to fructose and gluconic acid. The reactor system did not
show any loss in efficiency in a continuous operation over 20 days.
PMID- 29345757
TI - Whole genome sequencing analysis for cancer genomics and precision medicine.
AB - Explosive advances in next-generation sequencer (NGS) and computational analyses
have enabled exploration of somatic protein-altered mutations in most cancer
types, with coding mutation data intensively accumulated. However, there is
limited information on somatic mutations in non-coding regions, including
introns, regulatory elements and non-coding RNA. Structural variants and pathogen
in cancer genomes remain widely unexplored. Whole genome sequencing (WGS)
approaches can be used to comprehensively explore all types of genomic
alterations in cancer and help us to better understand the whole landscape of
driver mutations and mutational signatures in cancer genomes and elucidate the
functional or clinical implications of these unexplored genomic regions and
mutational signatures. This review describes recently developed technical
approaches for cancer WGS and the future direction of cancer WGS, and discusses
its utility and limitations as an analysis platform and for mutation
interpretation for cancer genomics and cancer precision medicine. Taking into
account the diversity of cancer genomes and phenotypes, interpretation of
abundant mutation information from WGS, especially non-coding and structure
variants, requires the analysis of large-scale WGS data integrated with RNA-Seq,
epigenomics, immuno-genomic and clinic-pathological information.
PMID- 29345760
TI - Application of temperature-sensitive mutants for single-cell protein production.
AB - Cell-division-cycle, temperature-sensitive mutants of Saccharomyces cerevisiae
were investigated as a means of altering the morphological characteristics and
subsequent physical properties of single-cell protein (SCP). Strain 4471,
harboring mutation cdc 4, formed a visible complex mass at the nonpermissive
temperature, after being grown at 30 degrees C and then transferred to 37 degrees
C for 8 hr. Microscopic observation showed that the mother cell was unable to
complete the budding process at the nonpermissive temperature, which caused the
cells to enlarge. Viscosity measurements were used to establish and characterize
optimum morphological changes in the yeast. The Maximum increase in viscosity
occurred when cells were incubated at 30 degrees C and then shifted to 37 degrees
C for 8 hr. Strain 4471 exhibited yield stress, whereas A364A did not. Maximum
change in yield stress occurred when cells were shifted from 30 to 37 degrees C
for 8 hr. No significant loss of protein or RNA occurred in strain 4471, as
compared to strain A364A, when incubated at the nonpermissive temperature.
PMID- 29345761
TI - The Brazilian ethanol program.
AB - Brazilian needs for petroleum as a primary energy source grew from 13.2% in 1940
to 41.7% in 1977. This resulted in a much greater dependence on foreign sources
and prompted the Government to initiate a detailed study of alternatives. The
National Alcohol Program established in 1975 is just one of the options being
examined. The National Energy Balance forecast shows that annual anhydrous
alcohol consumption for automotive purposes should increase from 1.74 * 106 m3 to
4.7 * 106 m3 in the period from 1978 to 1987. This paper presents the main
objectives of the National Alcohol Program in the context of the overall Energy
Program, points out the problems connected with alcohol production and
utilization, and reviews the serious problems related to its distribution to the
consuming centers. Finally, the indirect benefits resulting from the
implementation of the National Alcohol Program are shown, underlining the saving
of foreign currency, the substantial increase in employment opportunities, the
reduction in regional and individual income discrepancies, and the expansion of
capital goods production, together with the improvement of national technology in
the agricultural and industrial sectors.
PMID- 29345762
TI - Kinetic study on thermal stability of immobilized invertase.
AB - The kinetic study of the thermal stability of three kinds of invertases: native,
immobilized on porous glass covalently, and on ion-exchange resin ionically, has
been carried out, measuring their enzymatic activity for sucrose hydrolysis.
Thermal deactivations of all invertases obeyed first-order kinetics, being
independent of substrate concentration, with kd and DeltaEd , DeltaSd * as shown
in Tables I and II, respectively. Based on these parameter values, the effects of
immobilization and pH at deactivation on the stability have been considered, and
it was suggested that the ionic bond gives a more loosely deformed enzyme than
the covalent bond.
PMID- 29345763
TI - Modeling of rotating biological contactor systems.
AB - An investigation of the rotating biological contractor (RBC) process variables to
determine the efficiency of biological oxygen demand (BOD) removal is presented.
Operating parameters including influent BOD content (<355 mg/liter), flow rate,
disk surface area, hydraulic loading, disk rotational speed, liquid retention
time, stage number, and wastewater temperature were evaluated. The BOD predictive
model was developed using literature data with multiple regression analysis. This
study shows that influent BOD concentration, hydraulic loading, stage number, and
wastewater temperature are the most significant variables in predicting the RBC
system performance. The model presently developed was verified by field data
concerned with the treatment of both domestic and low-strength industrial
wastewaters. Also, the results calculated by this model were compared to those
obtained from Weng's model.
PMID- 29345764
TI - Characteristics of immobilized invertase.
AB - Five kinds of immobilized invertases (IMI)-covalently of porous glass and ion
exchange resins and ionically on ion-exchange resins-have been prepared and their
kinetic characteristics for sucrose hydrolysis, such as Km , K, pH profile, and
thermal stability were studied. Comparing the values of Km and activation energy
and the entropy of IMI with those of native invertase, it was concluded that the
immobilization influences not binding but kinetic specificity. The effects of the
immobilization method on thermal stability were also discussed.
PMID- 29345765
TI - Batch- and continuous-culture studies of a methane-utilizing mixed culture.
AB - A methane-utilizing mixed culture isolated from activated sludge by selective
enrichment at 45 degrees C was found to consist of three interacting species: a
methaneutilizing bacterium, a citrate-utilizing bacterium, and a methanol
utilizing bacterium. All three species grew well at 45 degrees C. Three different
stable mixed cultures were reconstituted by various combinations of these pure
cultures. The nutritional requirements and substrate ranges for each pure culture
were determined. The nutritional requirements and substrate ranges for each pure
culture were determined. The saturation constant for the methane-utilizing
bacterium on methane (K CH 4) and for the methanol-utilizing bacterium on
methanol (K CH 3OH) were 1.73 * 10-6 M and 4.51 * 10-7 M, respectively. The
volumetric mass transfer coefficient for methane (KL a) was determined to be 65.6
hr-1 .
PMID- 29345766
TI - Production of maltose and maltotriose from starch and pullulan by a immobilized
multienzyme of pullulanase and beta-amylase.
AB - Pullulanase was immobilized on tannic acid and TEAE-cellulose, and beta-amylase
was covalently immobilized on p-aminobenzylcellulose. Both the immobilized
enzymes showed similar properties in pH and temperature optima and heat
stability. On passing the pullulan solution at high temperature (50 degrees C)
through a column packed with immobilized pullulanase, only maltotriose was
obtained for ten days and the half-life was about 15 days. In a continuous
reaction using immobilized multienzyme, starch was completely converted into
maltose at 50 degrees C and at a space velocity of 1.2, a comparative longer half
life (20 days) was obtained. It was concluded that starch was smoothly converted
into maltose with the aid of alpha-amylase contaminated in the immobilized
pullulanase and the operational stability of the column increased with 2-5mM Ca2+
.
PMID- 29345767
TI - A quantitative description of the growth of Saccharomyces cerevisiae CBS 426 on a
mixed substrate of glucose and ethanol.
AB - Saccharomyces cerevisiae CBS 426 was grown aerobically in continuous culture with
a mixture of glucose and ethanol as the carbon source. The flows of biomass,
glucose, ethanol, oxygen, and carbon dioxide were measured. A model for growth
with two substrates was derived. Application of this model to the above-mentioned
system yielded values for YATP and P/O. The joint confidence regions for these
parameters were calculated. The relevance to industrial production of bakers'
yeast is discussed.
PMID- 29345768
TI - Immobilized catalase-containing yeast cells: Preparation and enzymatic
properties.
AB - The cell of Saccharomyces cerevisiae previously induced for catalase (EC
1.11.1.6) activity were immobilized by entrapment of intact cells in acrylamide
polymerized by gamma irradiation (100 kR). Yeast cells showed an enhancement in
catalase activity on entrapment, an effect similar to that observed on treatment
with organic solvents like toluene. The cells pretreated with toluene, however,
showed complete loss of catalase activity on entrapment. The entrapped enzyme
exhibited a narrow pH optimum, reduced Km for H2 O2 , and a decrease in
thermostability. The temperature optimum of catalase was also decreased from 60
to 40 degrees C on immobilization. A tenfold decrease in the activation energy
was also observed. The enzyme in the entrapped cells was, however, stable toward
inactivation by gamma irradiation. Unlike the intact cells, the entrapped yeast
cells did not have the ability to induce catalase.
PMID- 29345769
TI - Substrate utilization kinetic model for biological treatment process.
AB - The applicability of Contois' kinetic equation to aerobic and anaerobic
treatments of organic wastes is investigated. A refractory coefficient to account
for the nonbiodegradable portion of the organic substrates in the digester is
incorporated into the kinetic equation. The kinetic equation is applied to the
data for aerobic digestions of organic substrates and for anaerobic treatment of
dairy wastes. They all show a very good fit of the kinetic equation to the data.
Furthermore, the kinetic parameters and the refractory coefficients are shown to
be independent of influent organic substrate concentration. This study confirms
previous reports that the effluent quality of biological treatment systems for
organic wastes depends on influent organic waste concentration. The effect of
temperature on the kinetic parameters and the refractory coefficient for
anaerobic treatment of sewage sludge are studied. It shows that the kinetic
parameters vary with temperature, while the refractory coefficient remains fairly
constant. Equations to predict biodegradable treatment efficiency and volumetric
substrate utilization rate are also briefly discussed.
PMID- 29345770
TI - Interspecific interactions in a methane-utilizing mixed culture.
AB - A two-member methane-utilizing mixed culture of bacteria, formed by combining two
pure cultures isolated from a naturally occurring methane-utilizing mixed
culture, was studied in continuous culture. From the nutritional requirements and
substrate ranges of the pure cultures, a mechanism for the interspecific
interactions occurring in the mixed culture was proposed. Product formation
kinetics were determined in continuous culture for each product involved in the
proposed mechanism. From this proposed mechanism a mathematical model was derived
based on simple material balance equations around a single-stage chemostat. The
steady-state predictions of this model were compared to experimental results
obtained from continuous-culture experiments with the two-member methane
utilizing mixed culture. Interspecific interactions occurring in two-member
methanol-utilizing and three-member methane-utilizing mixed cultures have also
been discussed.
PMID- 29345771
TI - Reply to Wang and Kan.
PMID- 29345772
TI - Membrane responses induced by oligogalacturonides in suspension-cultured tobacco
cells.
PMID- 29345773
TI - Novel carbohydrate metabolism in the resurrection plant Craterostigma
plantagineum.
PMID- 29345774
TI - Rewiring Chemical Networks Based on Dynamic Dithioacetal and Disulfide Bonds.
AB - The control of the connectivity between nodes of synthetic networks is still
largely unexplored. To address this point we take advantage of a simple dynamic
chemical system with two exchange levels that are mutually connected and can be
activated simultaneously or sequentially. Dithioacetals and disulfides can be
exchanged simultaneously under UV light in the presence of a sensitizer.
Crossover reactions between both exchange processes produce a fully connected
chemical network. On the other hand, the use of acid, base or UV light connects
different nodes allowing network rewiring.
PMID- 29345775
TI - Versatile Modes of Cooperative B-H Bond Activation Reactions in Ruthenium-Carbene
Complexes: Addition, Ring-Opening and Insertion.
AB - Cooperative B-H bond activation reactions with thio- and iminophosphoryl tethered
ruthenium-carbene complexes are reported. The complexes show surprisingly
different reactivities towards the commonly employed boranes CatBH, PinBH and BH3
?LB as a result of different modes of metal-ligand cooperation. Although the
iminophosphoryl system allows for selective 1,2-addition of the B-H bond across
the Ru=C double bond, the sulfur analogue only delivers the 1,2-addition product
for CatBH, whereas activation of BH3 and PinBH lead to further insertion
reactions in one or more sides of the Ru-C-P-S-ring. The different reactivities
can be explained by the differences in the electronics of the carbene complexes
and the phosphoryl tether and by the Lewis acidities of the boranes. DFT
calculations show that the mechanism of the reactions either proceeds by an
addition across the Ru=C bond with different regioselectivities or across the Ru
S linkage.
PMID- 29345776
TI - Allyl Isothiocyanate Ameliorates Obesity by Inhibiting Galectin-12.
AB - SCOPE: The aim of this study is to investigate the signaling pathways by which
allyl isothiocyanate (AITC) reduces adipocyte differentiation and the efficacy of
AITC in suppressing galectin-12 levels as a therapeutic for high fat diet (HFD)
induced obesity. METHODS AND RESULTS: AITC presents anti-adipogenic effects on
3T3-L1 cells by decreasing lipid droplet accumulation in a dose-dependent manner.
AITC suppresses 3T3-L1 differentiation into adipocytes by decreasing galectin-12
expression and by downregulating key adipogenic transcription factors. AITC
influences the expression of 3T3-L1 pre-adipocytes by modulating adipokine
expression (leptin and resistin) and by regulating the protein kinase B
(PKB/Akt)/cAMP response element-binding protein (CREB) pathway. In HFD-fed mice,
oral administration of AITC reduces the body weight, accumulation of lipid
droplets in the liver, and white adipocyte size. CONCLUSION: In summary, the
results indicate that AITC inhibits adipocyte differentiation by suppressing
galectin-12 levels in 3T3L1 cells and has antiobesity effects in HFD-fed mice.
PMID- 29345777
TI - The occurrence and prevention of ethanol fermentation in high-dry-matter grass
silage.
AB - Ethanol is a common, usually minor fermentation product in ensiled forages, the
major product being lactic acid. Occasionally, high levels of ethanol are found
in silages. The aim of this study was to determine the incidence of high-dry
matter (DM) grass silages containing ethanol as the main fermentation product
(ethanol silages), to describe the fermentation process in such silages and to
determine the effect of grass maceration prior to wilting and addition of a
bacterial inoculant containing Lactobacillus plantarum and Enterococcus faecium
strains on fermentation. Twenty-one laboratory silages produced between 1993 and
1995, 21 farm silages produced between 1980 and 1989 and 36 farm silages produced
in 1995 (all produced without additive) were examined for pH and chemical
composition. Dry matter (DM) loss during ensilage was determined for the
laboratory silages only. Four laboratory silages were identified as ethanol
silages. Mean concentrations of ethanol, lactic acid and acetic acid were 48.1,
15.5 and 6.0 g kg-1 DM respectively. In the silages that contained lactic acid as
the main fermentation product (lactic acid silages) these values were 7.7, 45.5
and 15.1 g kg-1 DM. Mean DM loss and pH were 62.8 g kg-1 DM and 5.32 respectively
for ethanol silages and 24.4 g kg-1 DM and 4.69 for lactic acid silages. There
was no difference between ethanol silages and lactic acid silages in the mean
concentration of ammonia-N (94 g kg-1 total N), and butyric acid was not detected
(<0.2 g kg-1 DM), indicating that both types of silages were well preserved.
Analysis of the composition of the grass at ensiling showed a positive
correlation between the concentration of soluble carbohydrates and the
development into ethanol silage. Analysis of the farm silages indicated that 29%
of the silages produced between 1980 and 1989 and 14% of those produced in 1995
were ethanol silages. Maceration prior to wilting and addition of silage
inoculant improved lactic acid fermentation and prevented high ethanol levels.
The micro-organisms responsible for ethanol fermentation as well as the
implications of feeding ethanol silages to livestock remain to be resolved. (c)
2000 Society of Chemical Industry.
PMID- 29345778
TI - First confirmation in red wine of products resulting from direct anthocyanin
tannin reactions.
AB - Analysis of wine fractions before and after thiolysis confirmed the occurrence in
red wine of direct reactions between anthocyanins and tannins established earlier
in model solutions. Results showed the presence of two types of structures
differing in the linkage position of the anthocyanin moiety. On one hand,
detection of malvidin-3-glucoside (Mv3g) among thiolysis products revealed the
presence of anthocyanin-derived pigments in which Mv3g is linked by its C-6 or C
8 top. On the other hand, LC/MS analysis allowed the detection of two derivatives
tentatively identified as flavenes or a bicyclic condensation products yielded by
the reaction of a flavanol monomer (C-6 or C-8 top) with malvidin-3-glucoside (C
4 position). The presence of the corresponding benzylthioethers after thiolysis
of the polymeric fractions confirmed that procyanidins are similarly involved in
the latter reaction. Besides, MS also allowed the detection of new
benzylthioethers of catechin derivatives released after thiolysis of the wine
fractions, indicating that in addition to the postulated processes other types of
reactions take place in wines. (c) 2000 Society of Chemical Industry.
PMID- 29345779
TI - Kinetics of flavour and aroma changes in thermally processed cupuacu (Theobroma
grandiflorum) pulp.
AB - Changes in 'fresh' and 'cooked-notes' during thermal treatment of cupuacu
(Theobroma grandiflorum) pulp were evaluated and modelled. Isothermal experiments
in the temperature range of 70-98 degrees C were carried out and a non-linear
regression was performed to all data to estimate kinetic parameters. 'Fresh' and
'cooked-notes' change followed simple first-order (Ea = 78-82 kJ.mol-1 , z = 30
31 degrees C) and reversible first order (Ea = 80-85 kJ.mol-1 ) kinetics,
respectively. Although 'cooked-notes' were linearly correlated with 'fresh-notes'
(R2 = 0.99), the former was a better indicator for quality degradation. These
results are useful to design pasteurisation processes while minimising sensory
changes. (c) 2000 Society of Chemical Industry.
PMID- 29345780
TI - Influence of intramuscular fat content on lipid composition, sensory qualities
and consumer acceptability of cured cooked ham.
AB - The present study is part of a project which aims to examine the influence of
intramuscular fat (IMF) content on the sensory attributes and consumer
acceptability of pork. An experiment was conducted to evaluate the influence of
IMF level in muscle semimembranosus (SM) on the composition of its lipid fraction
and on the sensory qualities and consumer acceptability of cured cooked hams.
Thirty-two carcasses were selected 24 h after slaughter from 125 Duroc * Landrace
castrated male pigs showing large variability in SM muscle IMF content and were
assigned to four IMF groups: <=2%, 2-3%, 3-4% and >4%. Cured cooked ham slices
were evaluated by a trained expert panel of 12 members and by a group of 56
consumers. Results from lipid analyses indicate that (i) an increase in IMF
content was almost entirely reflected by an increase in the triglyceride content
of the muscle and (ii) higher IMF levels were associated with higher free fatty
acid and monoglyceride and lower cholesterol levels. The sensory evaluation of
marbling significantly increased with IMF level, whereas other sensory qualities
were unaffected. High IMF levels significantly depreciated the consumer
perception of fat, aspect, taste and smell of ham slices. Overall, slices with
the highest IMF levels got the least favourable rating by consumers. The present
study indicates that increased IMF levels in muscle semimembranosus do not have
significant effects on the sensory attributes of cured cooked hams, apart from
the perception of marbling. However, high IMF levels have detrimental effects on
the acceptability by consumers. (c) 2000 Society of Chemical Industry.
PMID- 29345781
TI - The yield and carcass chemical composition of impala (Aepyceros melampus), a
southern African antelope species.
AB - This investigation analyses the commercial carcass yields and chemical
composition of impala (Aepyceros melampus). The potential of this species for the
export market is also discussed. Impala rams (eight) and ewes (eight) cropped
commercially in Zimbabwe were found to have a similar dressout proportion (580 g
kg-1 ), although the males had a heavier live weight (49.4 +/- 4.606 kg) than the
females (33.5 +/- 3.417 kg). Sexual dimorphism was shown, with the males having
significantly (p < 0.01) heavier necks (69 +/- 5.47 g kg-1 ) and forequarters
(279 +/- 3.79 g kg-1 ) than the females (51 +/- 1.70 and 259 +/- 2.15 g kg-1
respectively) when expressed as a proportion of cold carcass weight (27.6 +/-
2.551 and 19.0 +/- 1.960 kg for males and females respectively). No sexual
effects (p > 0.2) were found in the mean chemical proximate composition of the 9
10-11 rib cut for the moisture (724.0 +/- 14.00 g kg-1 pooled sample), protein
(238.3 +/- 7.46 g kg-1 pooled sample) and ash (21.2 +/- 3.74 g kg-1 pooled
sample) contents. The females had a statistically higher (p = 0.0197) mean total
lipid content (33.9 +/- 1.705 g kg-1 ) than the males (24.5 +/- 3.171 g kg-1 ).
This investigation occurred at the end of the impala rut season, a period when
the rams not only consume less feed but also expend more energy owing to
strenuous activities in fighting for and maintaining a harem. (c) 2000 Society of
Chemical Industry.
PMID- 29345782
TI - Comparison of the expansion ability of fermented maize flour and cassava starch
during baking.
AB - The modifications occurring during the fermentation (at 20 or 35 degrees C) and
drying (under the sun or in an oven at 40 degrees C) of maize flour (ogi) and
cassava starch along with their expansion ability during baking were
characterised and compared. A high temperature accelerated the fermentation but
favoured lactic acid synthesis for maize ogi and butyric acid for cassava starch.
The increase in acidity was higher for maize, but dried maize ogi did not
evidence any expansion ability whatever the experimental conditions. Cassava
starch that had been fermented at 20 degrees C then sun-dried presented the
highest expansion ability. It was associated with low paste viscosities and high
swelling and solubilisation values. When the fermentation was carried out at 35
degrees C, an annealing of cassava starch occurred that delayed starch
gelatinisation and which could be involved in its lower baking expansion ability.
(c) 2000 Society of Chemical Industry.
PMID- 29345783
TI - Nutritional quality of complementary food prepared from unmalted and malted maize
fortified with cowpea using extrusion cooking.
AB - The nutritional quality of extruded unmalted or malted maize fortified with
cowpea as complementary food was assessed based on its proximate analysis, amino
acid composition and results from rat feeding with the blends. Results indicated
a slight decrease and increase in protein content due to malting and extrusion
respectively. The changes in fat, crude fibre and ash content were not
significant. The blends were a good source of energy, ranging from 1831 to 2045
kJ per 100 g. Extrusion significantly increased the amino acid content of the
blends, while malting had a varied effect on each of the amino acids. There was
no significant difference in the protein efficiency ratio (PER), net protein
ratio (NPR) and weight gain of rats fed the blends when compared with the control
(casein diet). The present study shows that malting improved the nutritional
quality of the blends. Rats fed the casein diet had higher values for total
digestibility (TD) and net protein utilisation (NPU). There was no significant
difference (P > 0.05) in the internal organ weights of rats fed all blends except
the protein-free diet. (c) 2000 Society of Chemical Industry.
PMID- 29345784
TI - Interaction between Maillard reaction products and lipid oxidation in starch
based model systems.
AB - The effect of Maillard reaction products (MRPs) on the kinetics of lipid
oxidation in intermediate-moisture model systems containing pregelatinised
starch, glucose, lysine and soybean oil has been studied. The samples, either
containing all components or excluding one or more of them, were heated at 100
degrees C for different times. Lipid oxidation and browning indices were measured
and the results confirmed the ability of MRPs to retard peroxide formation. Under
the conditions adopted, the rate of the Maillard reaction was increased by the
presence of the oil and its oxidation products. The antioxidant action of MRPs
was also evaluated using a peroxide-scavenging test based on crocin bleaching.
The results demonstrated that antioxidant activity developed with increased
browning of the samples. (c) 2000 Society of Chemical Industry.
PMID- 29345785
TI - Sequential hydrolysis of swine carcass samples and determination of amino acid
concentrations using pre-column derivatization with phenyl isothiocyanate.
AB - Comparing amino acid (AA) retention levels in pig carcass to true ileal
digestible AA intake provides an estimate of the marginal efficiency of AA
utilization. Accurate analysis of AA levels in the carcass samples is critical.
However, the standard 24 h of hydrolysis does not always provide maximum AA
values. A study was carried out to investigate the effect of hydrolysis time on
AA measurements in pig carcass. Correction factors to standardize AA levels to 24
h of hydrolysis were also determined. Ground carcass samples were hydrolysed with
6 mol litre-1 hydrochloric acid (HCl) in a 110 degrees C oven for nine different
time periods. Pre-column derivatization with phenyl isothiocyanate (PITC) was
used to determine AA concentrations in all of the samples. Hydrolysis time
significantly affected (P < 0.001) AA levels. The highest levels (P > 0.05) of
valine, isoleucine, serine, glycine, threonine, alanine, arginine, proline,
histidine and phenylalanine were not observed with 24 h hydrolysis. Therefore,
correction factors and sequential hydrolysis curves are important for these amino
acids. In conclusion, the effect of hydrolysis time should be considered in amino
acids analysis. (c) 2000 Society of Chemical Industry.
PMID- 29345786
TI - Existing and potential applications of ultraviolet light in the food industry - a
critical review.
AB - Short-wave ultraviolet light (UVC, 254 nm) can reduce dramatically the microbial
load in air or on hard surfaces free from food residues, and can eliminate
pathogens from potable water filtered to remove organic residues and 'clumps' of
bacteria. More recently, approval of the Food and Drug Administration (USA) has
been sought for a system for the destruction of pathogenic bacteria in fruit
juices using UVC, and the same approach could perhaps be applied to remove
spoilage organisms from cider or wines. In contrast, long-wave UV light (UVA,
>320 nm) has limited microbiocidal properties, and for practical applications its
effectiveness has to be enhanced by the presence of photosensitive compounds (eg
furocoumarins) that will diffuse into a microbial cell prior to irradiation. The
penetration of UVA into water is better than that of UVC, and its bacteriocidal
action in the presence of photosensitisers can be rapid. However, pure
furocoumarins are expensive and their addition to foodstuffs might be questioned
on safety grounds. (c) 2000 Society of Chemical Industry.
PMID- 29345787
TI - Development and application of soy-protein films to reduce fat intake in deep
fried foods.
AB - A soy protein film coating was developed and evaluated to reduce fat transfer in
deep-fried foods during frying. Soy protein isolate solutions (10% SPI) with
0.05% gellan gum as plasticizer cooled after being held at 80 degrees C for 20
min provided suitable films. There was a significant fat reduction (55.12 (+/
6.03)%db) between fried uncoated and coated discs of doughnut mix. The same films
were used on potato fries. Some panellists observed a slight difference between
the coated and uncoated fries but many preferred the coated fries over the
uncoated ones. Penetration test on potato fries showed no significant difference
between the texture of coated (SPI with gellan gum) and the uncoated fried
samples. A solution of 10% SPI with 0.05% gellan gum is recommended for coating
foods to reduce fat intake during deep-fat frying. (c) 2000 Society of Chemical
Industry.
PMID- 29345788
TI - Activities of phospholipases A and lysophospholipases in glycolytic and oxidative
skeletal muscles in the rabbit.
AB - Oxidative muscles contain more free fatty acids than glycolytic muscles, which
could explain in part their higher sensitivity to oxidation. These fatty acids
are partly the result of phospholipid hydrolysis catalysed by phospholipases A
and lysophospholipases. Up to now, very little is known on the activities of
these enzymes in skeletal muscles. This study deals with the activities of
phospholipases A and lysophospholipases in five rabbit muscles covering a large
range of metabolic types (oxidative Soleus and Semimembranosus proprius muscles,
glycolytic Psoas major and Longissimus lumborum muscles and intermediate
Gastrocnemius laterale muscle). The results showed that (a) phospholipases A and
lysophospholipases had maximal activity at pH 8-9; (b) phospholipases A and
lysophospholipases retained more than 50% of their maximal activity at pH 5.5-6,
the ultimate pH of muscles; (c) lysophospholipases exhibited a higher activity
than phospholipases A (4-7-fold higher in the oxidative muscles, 11-fold higher
in the intermediate muscle and 18-23-fold higher in the glycolytic muscles); and
(d) phospholipase A and lysophospholipase activities were higher in oxidative
muscles than in glycolytic muscles (10-25-fold higher for phospholipases A and 4
5-fold higher for lysophospholipases). Thus oxidative muscles have a higher
potential activity for post-mortem hydrolysis of phospholipids. (c) 2000 Society
of Chemical Industry.
PMID- 29345789
TI - A mathematical model for colour loss in paprikas containing differing proportions
of seed.
AB - In this paper a general kinetic model for predicting the colour of paprikas with
differing proportions of seed as a function of the storage conditions is
developed. We apply this model to study the effect of time and storage conditions
on colour loss in paprikas made from the same pepper variety, Ocal, but with
differing proportions of seed. The agreement between the experimental colour data
for this paprika and the results predicted by the mathematical model is very
good. Both the model and the experimental data show that the rate of colour loss
decreases with increasing proportion of seed, and after a determined inversion
time the samples with the lowest initial colour values actually show the highest
values. Likewise, the experimental data show that for a given proportion of seed
the colour loss decreases as the storage relative humidity increases. (c) 2000
Society of Chemical Industry.
PMID- 29345790
TI - Evaluating two kinds of centrifuged virgin oils arising from continuous olive
processing.
AB - Oils extracted from olive pastes by the direct centrifugation mode were compared
with the homologous oils produced by the indirect centrifugation (after
percolation) mode. The former were characterised by: (i) higher contents of total
phenols, o-diphenols, hydroxytyrosol, hydroxytyrosol-aglycons, total volatiles,
trans-2-hexanal and other pleasant volatiles, total tocopherols, total sterols
and waxes; (ii) lower contents of triterpene dialcohols, aliphatic and triterpene
alcohols, chlorophylls and pheophytins; (iii) lower values of integral colour
index; (iv) higher values of turbidity, campesterol/stigmasterol ratio, 1,2
diglycerides/1,3-diglycerides ratio, oxidative stability and overall quality
indices; and (v) higher sensory score. Stigmastadienes and trans-isomer C18 fatty
acids were always not detected. The average oil outputs of the two centrifugation
extraction procedures were comparable, as confirmed by similar overall oil
amounts found in the by-products. (c) 2000 Society of Chemical Industry.
PMID- 29345791
TI - Characterisation of peptides in silages made from perennial ryegrass with
different silage additives.
AB - The effects of applying either formic acid (5.4 g kg-1 ), a mixture of formic
acid (2.7 g kg-1 ) and formaldehyde (1.5 g kg-1 , 81 g kg-1 herbage crude
protein) or two concentrations of a cysteine peptidase inhibitor, cystamine (5 or
50 g kg-1 ), to perennial ryegrass (Lolium perenne) on the nitrogen (N)
distribution of the resulting silages were investigated, with emphasis on changes
in concentration, composition and molecular weight of silage peptides. Herbage
(156 g dry matter kg-1 and 141 g water-soluble carbohydrate kg-1 dry matter) was
ensiled in triplicate in laboratory silos for 100 days. Formic acid and the
formic acid/formaldehyde mixture reduced soluble non-protein N and ammonia N
concentrations (P < 0.01); in addition, formic acid increased peptide N
concentrations (P < 0.05). Cystamine at 50 g kg-1 reduced ammonia N
concentrations (P < 0.01) and increased peptide N concentrations (P < 0.05), but
when applied at 5 g kg-1 had little effect. Gel filtration of silage extracts on
Sephadex G-25 suggested that a small proportion (0.06-0.11 g kg-1 peptide N) of
silage peptides had a chain length of 7-9 amino acids, but remaining peptides
were smaller with chain lengths of 2-6 amino acid residues. Amino acid analysis
of silage peptides indicated that additive treatment had little effect on peptide
amino acid composition but that peptides with a chain length of 7-9 amino acids
contained lower proportions of isoleucine and arginine. (c) 2000 Society of
Chemical Industry.
PMID- 29345792
TI - Location of and post-mortem changes in some cytoskeletal proteins in pork and cod
muscle.
AB - The cytoskeletal proteins actin, nebulin, spectrin, desmin, vinculin and talin
were labelled immunohistochemically in sections of muscle from commercially
available pigs and cod (Gadus morhua) taken pre-rigor and from samples stored for
several days. Actin, nebulin and spectrin gave similar labelling patterns in both
pork and cod muscle which remained the same in stored samples. Desmin was
intensely labelled at the cell boundaries and within the body of the cells in
both pork and cod in the initial and the stored samples. Vinculin was readily
labelled in pork muscle but showed only diffuse labelling in fish. Labelling for
talin in pork muscle was intense at the sarcolemma but was not present in samples
stored for 4 days. In contrast, the label for talin was concentrated at the
myotendinous junction of the cod muscle throughout the storage period. These are
the first reports of the detection and location of spectrin and vinculin in fish
muscle and of the location of talin. The results are discussed in terms of muscle
structure, function and post-mortem tenderisation. (c) 2000 Society of Chemical
Industry.
PMID- 29345793
TI - Characteristics of nixtamalised maize flours produced with the use of microwave
heating during alkaline cooking.
AB - Whole, ground and abrasively dehulled grains from both normal (H-34 and H-34) and
quality protein (QPM and QPMa) maize were mixed with water contents of 70, 95 and
100 g kg-1 and calcium hydroxide concentrations of 0.0, 0.3, 0.5 and 2.0 g kg-1
and heated (operating frequency 2.450 MHz, high-power setting) for 10, 15 and 20
min in a commercial microwave oven. The cooked grain was then oven dried and
milled to obtain nixtamalised maize flour (NMF). The protein contents and test
weights of QPM were higher than for the normal hybrids. The highest yields of
masa and tortillas were found for the normal hybrids, and these samples did not
show significant differences, as compared with the commercial nixtamalised flour
(CNMF) used as control, with respect to masa firmness and adhesiveness and
tortilla tensile strength. The cutting force of tortillas from hybrid H-30 and
QPM did not show significant differences from the control. The highest values of
tortilla rollability were found for the control followed by hybrid H-34. The
values of residual cooking liquor for microwave-heated samples were lower than
for the control. Ground or dehulled maize grain gave sticky masa and poor
mechinical characteristics. Tortillas from whole grain showed good
characteristics of texture and consistency of masa, and the tortillas were
subjectively similar in colour, flavour and rollability to the tortillas prepared
with CNMF. These results indicate a potential use of microwave energy to produce
NMF for tortillas and derivatives. (c) 2000 Society of Chemical Industry.
PMID- 29345794
TI - A modified laboratory canning protocol for quality evaluation of dry bean
(Phaseolus vulgaris L).
AB - The effects of calcium (Ca2+ ) level in the soak water, blanch water and brine,
blanching temperature, and total seed solids on dry bean canning quality were
investigated to optimise a laboratory canning protocol. A linear increase in the
Ca2+ level of soak water, blanch water and brine resulted in a linear decrease in
hydration coefficient and percent washed drained weight but a linear increase in
texture. Low Ca2+ level (10 mg kg-1 ) reduced the hydration time for dry bean
seed from 14 to 1 h. Blanching temperatures of 50, 70 and 88 degrees C had non
significant effects on canning quality traits. Blanching for 30 min at 70
degrees C for black bean or at 88 degrees C for navy bean and pinto bean
resulted in percent washed drained weight >= 60, as required by the Canada
Agricultural Products Standards Act. Seed solids levels of 95-97 g per 300 * 407
(14 fl oz) can were sufficient to attain a percent washed drained weight of 60.
It was confirmed that the thermal processing conditions (115.6 degrees C retort
temperature, 45 min) used in this study were sufficient to achieve commercial
sterility. The optimised lab protocol for evaluation of the canning quality of
dry bean breeding lines is as follows. Seed containing 95 g of solids for pinto
bean, 96 g for navy bean and 97 g for black bean is soaked in water for 30 min at
20 degrees C and blanched for 30 min at 70 degrees C for black bean and 88
degrees C for navy bean and pinto bean in water containing 10 mg kg-1 of Ca2+ .
The seed is then transferred to a 300 * 407 can, filled with brine containing 10
mg kg-1 of Ca2+ , 1.3% (w/v) of NaCl and 1.6% (w/v) of sugar. The can is then
sealed, processed in steam at 115.6 degrees C for 45 min and cooled at 20
degrees C for 20 min. Cans are stored for at least 2 weeks prior to quality
evaluation of the canned product. Canning of dry bean seed according to this
protocol results in precise estimation of canning quality traits, particularly
percent washed drained weight. (c) 2000 Society of Chemical Industry.
PMID- 29345795
TI - Combined effect of high pressure, temperature and holding time on
polyphenoloxidase and peroxidase activity in banana (Musa acuminata).
AB - Polyphenoloxidase and peroxidase enzyme activities were evaluated following
combined pressure, temperature and holding time treatment in banana (Musa
acuminata). Using pressures of up to 110 MPa, temperatures of up to 70 degrees C
and holding times of up to 25 min, based on a 23 central composite design, the
interactive effects were found to significantly influence the activity of both
enzymes in prepared banana pulp. Temperature and pressure were found to influence
the inactivation of polyphenoloxidase separately, while temperature, pressure and
holding time were found to influence the loss of peroxidase in the banana,
although no significant interactive effects were found. The reduction in
polyphenoloxidase activity was found to be less influenced by the combined
treatment than peroxidase activity, thought to be due to solubilisation of the
enzyme and effects of the soluble solids content. (c) 2000 Society of Chemical
Industry.
PMID- 29345796
TI - Physicochemical and rheological characteristics of commercial nixtamalised
Mexican maize flours for tortillas.
AB - Three commercial nixtamalised Mexican maize flours (CNMFs) designated HI-A, HI-B
and HI-C were evaluated in this work. For each brand, four samples corresponding
to four consecutive months of production were evaluated. Tortillas prepared by
the traditional process of nixtamalisation were used as the control. The maize
flours and their respective tortillas showed variations between samples in their
physical, chemical and rheological parameters. The three commercial maize flours
incorporated additives and preservatives. The moisture content, colour, pH,
subjective water absorption capacity, water solubility index, water absorption
index and swelling capacity of flours showed strong differences between the three
CNMFs with respect to the chemical analysis. Important differences in the
protein, calcium and amylose contents were observed. Tortillas from CNMFs had a
blander maize flavour, less desirable texture and staled more rapidly than
traditional tortillas. Some modifications are required in the current Official
Mexican Quality Standard, principally in the appropriate selection of additives
and levels used in the preparation of CNMFs. (c) 2000 Society of Chemical
Industry.
PMID- 29345797
TI - Changes in the carotenoid content of apricot (Prunus armeniaca, var Bergeron)
during enzymatic browning: beta-carotene inhibition of chlorogenic acid
degradation.
AB - Considering the numerous beneficial effects in human health ascribed to
carotenoids, studies were performed to investigate the modification of carotenoid
amount and composition during apricot enzymatic browning. First works on bruised
apricot purees have shown a trans-beta-carotene isomerisation (20%) induced by
enzymatic browning. To clarify this isomerisation, oxidation of chlorogenic acid
in presence of trans-beta-carotene, catalysed by purified apricot
polyphenoloxidase (PPO), was followed by HPLC and polarography. Isomerisation
rate of trans-beta-carotene in its cis isomer was found to increase with
chlorogenic acid concentration. Moreover, trans-beta-carotene was shown to be a
potent inhibitor of phenol degradation. This inhibition was partially ascribed to
PPO inhibition (non-competitive inhibitor towards phenol with an apparent Ki
close to 0.5 mM, a mixed type inhibitor towards oxygen with an apparent Ki close
to 0.15 mM). The additional inhibition was explained by non-enzymatic reactions
involving trans-beta-carotene and chlorogenic acid o-quinones and leading to
phenol regeneration and carotene isomerisation. (c) 2000 Society of Chemical
Industry.
PMID- 29345798
TI - Clinical impact of pharmacokinetic interactions between the HCV protease
inhibitor simeprevir and frequently used concomitant medications.
AB - AIMS: Direct-acting antiviral agents (DAAs) for the treatment of hepatitis C
(HCV) can be associated with drug-drug interactions (DDIs) with concomitant
medications. The practical clinical implications of such DDIs are poorly
understood. We assessed the clinical impact of possible pharmacokinetic (PK)
interactions between simeprevir and frequently prescribed concomitant
medications. METHODS: This post hoc analysis pooled data from nine studies which
evaluated simeprevir (SMV)-based interferon-free HCV treatment. Three classes of
frequently used concomitant medications of interest (CMOIs) were analysed
[antihypertensive drugs (AHDs), anxiolytic drugs (AXDs) and lipid-lowering drugs
(LLDs)] and categorized as amber or green according to their DDI potential with
SMV (green: no DDIs; amber: potential/known PK interactions). Concomitant
medications not recommended to be coadministered with SMV were not included. The
composite primary endpoint was defined as the frequency of either
discontinuation, interruption or dose modification of the CMOI during 12 weeks of
SMV treatment. RESULTS: Few patients met the composite endpoint in the various
subgroups. Patients on amber CMOIs tended to experience CMOI modification more
often (13.4-19.4%) than those on green CMOIs (3.1-10.8%). There was no difference
in the frequency of adverse events between patients taking green and those taking
amber CMOIs. CONCLUSIONS: In this large pooled analysis, coadministration of the
evaluated commonly prescribed medications with known or potential PK interactions
with SMV was manageable and resulted in few adjustments of concomitant
medications. Our method could serve as a blueprint for the evaluation of the
impact of DDIs.
PMID- 29345799
TI - Self-criticism self-report measures: Systematic review.
AB - PURPOSE: Self-criticism is a transdiagnostic process that has been attracting
research and clinical interest. The accurate measurement of this construct is
therefore crucial; however, there are currently numerous measures of self
criticism and no guidelines about which to use in different contexts. This
systematic review evaluated the measurement properties of self-report
questionnaires of self-criticism. METHODS: OvidSP and Web of Science were used to
search through multiple databases, and an initial grey literature search was
completed. Studies were included when the main focus was to evaluate the
measurement properties of English version of scales or subscales that aimed to
measure self-criticism in an adult population. Both the methodological quality of
included studies and the specific measurement properties were evaluated; these
ratings were then combined into a best evidence synthesis. RESULTS: Five scales
and five subscales were identified, described in 16 papers. The scales were
designed to measure different types of self-criticism including trait or
repetitive self-criticism and self-criticism in response to difficult situations
or as a mood regulation strategy. The majority of included studies were either
rated as having poor methodological quality, or were given indeterminate or
negative ratings for the measurement properties they reported. Questionnaire
content varied depending on how the authors conceptualized self-criticism. Issues
were also highlighted in relation to the checklist used to rate methodological
quality. CONCLUSIONS: Tentative recommendations were made about two measures of
self-criticism based on existing evidence; future research is required.
Furthermore, questionnaire choice should be based on the type of self-criticism
being assessed. PRACTITIONER POINTS: Self-criticism has been associated with a
range of clinical difficulties including depression and eating disorders and is
increasingly the focus of research, including treatment studies directly
targeting self-criticism. Since different researchers have conceptualized self
criticism differently, a number of self-criticism self-report questionnaires have
been developed that vary in terms of design, structure, and content. This
systematic review identified and evaluated the measurement properties of self
report questionnaires of self-criticism and makes tentative recommendations about
their use in clinical and research settings and areas for future research.
PMID- 29345800
TI - Haplotype-based genotyping-by-sequencing in oat genome research.
AB - In a de novo genotyping-by-sequencing (GBS) analysis of short, 64-base tag-level
haplotypes in 4657 accessions of cultivated oat, we discovered 164741 tag-level
(TL) genetic variants containing 241224 SNPs. From this, the marker density of an
oat consensus map was increased by the addition of more than 70000 loci. The
mapped TL genotypes of a 635-line diversity panel were used to infer chromosome
level (CL) haplotype maps. These maps revealed differences in the number and size
of haplotype blocks, as well as differences in haplotype diversity between
chromosomes and subsets of the diversity panel. We then explored potential
benefits of SNP vs. TL vs. CL GBS variants for mapping, high-resolution genome
analysis and genomic selection in oats. A combined genome-wide association study
(GWAS) of heading date from multiple locations using both TL haplotypes and
individual SNP markers identified 184 significant associations. A comparative
GWAS using TL haplotypes, CL haplotype blocks and their combinations demonstrated
the superiority of using TL haplotype markers. Using a principal component-based
genome-wide scan, genomic regions containing signatures of selection were
identified. These regions may contain genes that are responsible for the local
adaptation of oats to Northern American conditions. Genomic selection for heading
date using TL haplotypes or SNP markers gave comparable and promising prediction
accuracies of up to r = 0.74. Genomic selection carried out in an independent
calibration and test population for heading date gave promising prediction
accuracies that ranged between r = 0.42 and 0.67. In conclusion, TL haplotype GBS
derived markers facilitate genome analysis and genomic selection in oat.
PMID- 29345802
TI - The EAA International Quality Control Programme for Y-Chromosomal Microdeletions.
PMID- 29345801
TI - Individual psychological therapy in an acute inpatient setting: Service user and
psychologist perspectives.
AB - OBJECTIVES: The acute inpatient setting poses potential challenges to delivering
one-to-one psychological therapy; however, there is little research on the
experiences of both receiving and delivering therapies in this environment. This
qualitative study aimed to explore service users' and psychologists' experiences
of undertaking individual therapy in acute inpatient units. It focused on the
relationship between service users and psychologists, what service users found
helpful or unhelpful, and how psychologists attempted to overcome any challenges
in delivering therapy. DESIGN: The study used a qualitative, interview-based
design. METHODS: Eight service users and the six psychologists they worked with
were recruited from four acute inpatient wards. They participated in individual
semi-structured interviews eliciting their perspectives on the therapy. Service
users' and psychologists' transcripts were analysed together using Braun and
Clarke's (2006, Qualitative Research in Psychology, 3, 77) method of thematic
analysis. RESULTS: The accounts highlighted the importance of forming a 'human'
relationship - particularly within the context of the inpatient environment - as
a basis for therapeutic work. Psychological therapy provided valued opportunities
for meaning-making. To overcome the challenges of acute mental health crisis and
environmental constraints, psychologists needed to work flexibly and creatively;
the therapeutic work also extended to the wider context of the inpatient unit, in
efforts to promote a shared understanding of service users' difficulties.
CONCLUSIONS: Therapeutic relationships between service users and clinicians need
to be promoted more broadly within acute inpatient care. Psychological
formulation can help both service users and ward staff in understanding crisis
and working collaboratively. Practice-based evidence is needed to demonstrate the
effectiveness of adapted psychological therapy models. PRACTITIONER POINTS:
Developing 'human' relationships at all levels of acute inpatient care continues
to be an important challenge for clinical practice. Due to the distress of
individuals and the constraints of the acute inpatient environment, psychologists
need to be flexible and adaptable in delivering individual therapy. Making
meaning and psychological formulation can give service users a sense of hope and
empowerment, and can contribute to a shared understanding within the ward team of
service users' difficulties.
PMID- 29345803
TI - Effects of mindfulness-based cognitive therapy on shame, self-compassion and
psychological distress in anxious and depressed patients: A pilot study.
AB - OBJECTIVES: The tendency to experience shame or guilt is associated
differentially with anxiety and depression, with shame being associated with
greater psychopathology. Correlational studies have shown self-compassion to be
related to lower shame and rumination, and mindfulness-based interventions
increase self-compassion. Therefore, mindfulness-based interventions may decrease
shame. This pilot study aimed to assess the association of shame, rumination,
self-compassion, and psychological distress and the effects of a mindfulness
based intervention on these measures in a clinical sample. DESIGN: Single-group
design with pre-test and post-test measures. METHOD: Thirty-two service users who
experienced clinically diagnosed depressive or anxiety disorders in a mindfulness
based cognitive therapy programme were assessed before and twenty-two after
therapy with measures of shame-proneness, external shame, rumination, self
compassion, and psychological distress. RESULTS: Shame-proneness and external
shame were positively correlated with self-coldness, and external shame was
positively correlated with stress and depressive symptoms. Self-compassion
increased and self-coldness decreased, while shame-proneness, rumination,
anxiety, and stress symptoms decreased from pre- to post-treatment. There was no
significant reduction in depressive symptoms, guilt-proneness, or external shame.
CONCLUSION: Our preliminary findings suggest that mindfulness-based approaches
may be helpful in increasing self-compassion and reducing shame-proneness in
mixed groups of anxious and depressed patients. Controlled studies of the effects
of mindfulness-based interventions on shame in clinical populations are
warranted. PRACTITIONER POINTS: Shame-proneness and external shame showed
different patterns of relationship with depressive and stress symptoms and with
self-compassion. Shame-proneness decreased to a greater extent than external
shame decreased following participation in an MBCT group. Mindfulness-based
interventions may benefit shame-proneness to a greater extent than external
shame.
PMID- 29345804
TI - MoP Nanoparticles Supported on Indium-Doped Porous Carbon: Outstanding Catalysts
for Highly Efficient CO2 Electroreduction.
AB - Electrochemical reduction of CO2 into value-added product is an interesting area.
MoP nanoparticles supported on porous carbon were synthesized using metal-organic
frameworks as the carbon precursor, and initial work on CO2 electroreduction
using the MoP-based catalyst were carried out. It was discovered that MoP
nanoparticles supported on In-doped porous carbon had outstanding performance for
CO2 reduction to formic acid. The Faradaic efficiency and current density could
reach 96.5 % and 43.8 mA cm-2 , respectively, when using ionic liquid 1-butyl-3
methylimidazolium hexafluorophosphate as the supporting electrolyte. The current
density is higher than those reported up to date with very high Faradaic
efficiency. The MoP nanoparticles and the doped In2 O3 cooperated very well in
catalyzing the CO2 electroreduction.
PMID- 29345805
TI - Is the widely used two-factor structure of the Ruminative Responses Scale
invariant across different samples of women?
AB - OBJECTIVES: Although the Ruminative Responses Scale is one of the most widely
used measures of rumination, its two-factor structure remains controversial.
Taking this into account, we aimed to test the RRS-10 two-factor invariance
(Brazilian version) between different samples of women and to study its internal
consistency and convergent validity. METHODS: A sample of 321 women (general
population, n = 106; college students, n = 115; and medical population of
patients with overweight and obesity, n = 100) participated in the study. The two
factor structure of RRS-10 was assessed by CFA and multigroup analysis using
Mplus software. Internal consistency was assessed by Cronbach's alpha and the
convergent validity by Pearson correlations. RESULTS: The two-factor structure of
RRS-10 showed a good fit, factorial invariance across three samples, good
internal consistency, and adequate convergent validity. Brooding and Reflection
subscales were both positively correlated with psychological inflexibility,
cognitive fusion, anxiety, depression, and stress symptoms, although Brooding
presented significantly stronger associations with these variables than
Reflection. CONCLUSIONS: This study provides further discussion and evidence
regarding the RRS-10 two-factor structure, as well as a valid version of RRS-10
to use in Brazil in order to reliably assess rumination in medical and research
settings. PRACTITIONER POINTS: This is the first study to test and confirm the
RRS two-factor structure invariance across groups. RRS-10 two-dimensionality was
confirmed in medical and non-medical samples of women. Brooding subscale showed
significantly stronger relationships with psychopathology and experiential
avoidance than Reflection. The study provides evidence that RRS can be used as a
valid and sound measure to accurately assess the clinically relevant dimensions
of rumination simultaneously across distinct groups.
PMID- 29345806
TI - Response to Dr. Finucane.
PMID- 29345807
TI - Targeting a Dark Excited State of HIV-1 Nucleocapsid by Antiretroviral Thioesters
Revealed by NMR Spectroscopy.
AB - HIV-1 nucleocapsid (NCp7) is a two Cys2 HisCys zinc knuckle (N-Zn and C-Zn)
protein that plays a key role in viral replication. NCp7 conformational dynamics
is characterized by NMR relaxation dispersion and chemical exchange saturation
transfer measurements. While the N-Zn knuckle is conformationally stable, the C
Zn knuckle interconverts on the millisecond timescale between the major state, in
which the zinc is coordinated by three cysteines and a histidine, and two folded
minor species (with populations around 1 %) in which one of the coordination
bonds (Cys413-Sgamma-Zn or His421-Nepsilon2-Zn) is hydrolyzed. These findings
explain why antiretroviral thioesters specifically disrupt the C-Zn knuckle by
initial acylation of Cys413, and show that transient, sparsely-populated
("dark"), excited states of proteins can present effective targets for rational
drug design.
PMID- 29345808
TI - Immune protective effects of chitooligosaccharides on mice genital tract infected
by Chlamydia trachomatis.
AB - PROBLEM: The immune protective effects of chitooligosaccharides (COs) on mouse
genital tract infected by Chlamydia trachomatis (Ct) were unknown. METHODS: The
minimum effective/infective dose was obtained by establishing the murine model of
the genital tract infected by Ct. The model mice were treated with different
doses (0.1, 0.2, and 0.3 g/kg,) of COs and 0.9% saline, and the serum
immunoglobulin G (IgG) antibody and interleukin (IL)-11 levels were then assayed.
The healthy mice were used as the control. After 1 week of immunity, a double
effective/infective dose of Ct was used to attack the genital tract. After 10
days of experiment, the mice were killed, their spleen and thymus indexes were
determined, and the pathological changes in their genital tract were evaluated.
RESULTS: Treatment with COs increased the serum IgG antibody, IL-11 levels, and
spleen and thymus indexes but decreased the positive infection rate and inclusion
body formation with Ct. CONCLUSION: COs could induce immune protection on the Ct
infected mouse genital tract and might be used as an alternative drug for the
treatment of genital tract infected with Ct.
PMID- 29345809
TI - Peroxisomes in lipid metabolism.
AB - Gene targeting and the elucidation of mutations underlying inherited peroxisomal
diseases have provided new insights in peroxisomal lipid metabolism in vivo. The
work led to the identification of a novel peroxisomal beta-oxidation pathway and
established clearly that genes, which are required for efficient peroxisomal
oxidation of fatty acids, at the same time are key regulators of PPARalpha
function in vivo. The new mouse models may provide helpful tools in the search
for unknown natural PPARalpha agonists and in screening for in vivo PPARalpha
antagonists. J. Cell Biochem. Suppls. 30/31:158-167, 1998. (c) 1998 Wiley-Liss,
Inc.
PMID- 29345810
TI - Communication between the cell membrane and the nucleus: Role of protein
compartmentalization.
AB - Understanding how the information is conveyed from outside to inside the cell is
a critical challenge for all biologists involved in signal transduction. The flow
of information initiated by cell-cell and cell-extracellular matrix contacts is
mediated by the formation of adhesion complexes involving multiple proteins.
Inside adhesion complexes, connective membrane skeleton (CMS) proteins are signal
transducers that bind to adhesion molecules, organize the cytoskeleton, and
initiate biochemical cascades. Adhesion complex-mediated signal transduction
ultimately directs the formation of supramolecular structures in the cell
nucleus, as illustrated by the establishment of multi complexes of DNA-bound
transcription factors, and the redistribution of nuclear structural proteins to
form nuclear subdomains. Recently, several CMS proteins have been observed to
travel to the cell nucleus, suggesting a distinctive role for these proteins in
signal transduction. This review focuses on the nuclear translocation of
structural signal transducers of the membrane skeleton and also extends our
analysis to possible translocation of resident nuclear proteins to the membrane
skeleton. This leads us to envision the communication between spatially distant
cellular compartments (i.e., membrane skeleton and cell nucleus) as a
bidirectional flow of information (a dynamic reciprocity) based on subtle
multilevel structural and biochemical equilibria. At one level, it is mediated by
the interaction between structural signal transducers and their binding partners,
at another level it may be mediated by the balance and integration of signal
transducers in different cellular compartments. J. Cell. Biochem. Suppls.
30/31:250-263, 1998. (c) 1998 Wiley-Liss, Inc.
PMID- 29345811
TI - Osteopontin expression and function: Role in bone remodeling.
AB - The cytokine and cell attachment protein osteopontin (OPN) is not necessary for
the development and survival of mice in a clean animal facility. The primary role
of OPN appears to be that of facilitating recovery of the organism after injury
or infection, which generally causes an increase in its expression. It also is
essential for some forms of bone remodeling. OPN stimulates cellular signaling
pathways via various receptors found on most cell types and can encourage cell
migration. OPN modulates immune and inflammatory responses and possibly
negatively regulates Ras signaling pathways. Its apparent ability to enhance cell
survival by inhibiting apoptosis may explain why the metastatic proficiency of
tumor cells increases with increased OPN expression. J. Cell. Biochem. Suppls.
30/31:92-102, 1998. (c) 1998 Wiley-Liss, Inc.
PMID- 29345812
TI - Role of histone deacetylases in acute leukemia.
AB - Accumulating evidence points to a connection between cancer and transcriptional
control by histone acetylation and deacetylation. This is particularly true with
regard to the acute leukemias, many of which are caused by fusion proteins that
have been created by chromosomal translocations. Genetic rearrangements that
disrupt the retinoic acid receptor-alpha and acute myeloid leukemia-1 genes
create fusion proteins that block terminal differentiation of hematopoietic cells
by repressing transcription. These fusion proteins interact with nuclear hormone
co-repressors, which recruit histone deacetylases to promoters to repress
transcription. This finding suggests that proteins within the histone deacetylase
complexes may be potential targets for pharmaceutical intervention in many
leukemia patients. J. Cell. Biochem. Suppls. 30/31:194-202, 1998. (c) 1998 Wiley
Liss, Inc.
PMID- 29345813
TI - High throughput analysis of differential gene expression.
AB - Elucidation of the changes in gene expression associated with biological
processes is a central problem in biology. Advances in molecular and
computational biology have led to the development of powerful, high-thoughput
methods for the analysis of differential gene expression. These tools have opened
up new opportunities in disciplines ranging from cell and developmental biology
to drug development and pharmacogenomics. In this review, the attributes of five
commonly used differential gene expression methods are discussed: expressed
sequence tag (EST) sequencing, cDNA microarray hybridization, subtractive
cloning, differential display, and serial analysis of gene expression (SAGE). The
application of EST sequencing and microarray hybridization is illustrated by the
discovery of novel genes associated with osteoblast differentiation. The
application of subtractive cloning is presented as a tool to identify genes
regulated in vivo by the transcription factor pax-6. These and other examples
illustrate the power of genomics for discovering novel genes that are important
in biology and which also represent new targets for drug development. The central
theme of the review is that each of the approaches to identifying differentially
expressed genes is useful, and that the experimental context and subsequent
evaluation of differentially expressed genes are the critical features that
determine success. J. Cell. Biochem. Suppls. 30/31:286-296, 1998. (c) 1998 Wiley
Liss, Inc.
PMID- 29345814
TI - Promiscuous subunit interactions: A possible mechanism for the regulation of
protein kinase CK2.
AB - Protein kinase CK2 is a ubiquitous eukaryotic ser/thr protein kinase. The active
holoenzyme is a heterotetrameric protein composed of catalytic (alpha and alpha')
and regulatory (beta) subunits that phosphorylates many different protein
substrates and appears to be involved in the regulation of cell division. Despite
important structural studies, the intimate details of the interactions of the
alpha catalytic subunits with the beta regulatory subunits are unknown. Recent
evidence that indicates that both CK2 subunits can interact promiscuously with
other proteins in a manner that excludes the binding of their complementary CK2
partners has opened the possibility that the phosphorylating activity of this
enzyme may be regulated in a novel way. These alternative interactions could
limit the in vivo availability of CK2 subunits to generate fully active
holoenzyme CK2 tetramers. Likewise, variations in the ratio of alpha- and beta
subunits could determine the activity of several phosphorylating and
dephosphorylating activities. The promiscuity of the CK2 subunits can be
extrapolated to a more widespread phenomenon in which "wild-card" proteins could
act as general switches by interacting and regulating several catalytic
activities. J. Cell. Biochem. Suppls. 30/31:129-136, 1998. (c) 1998 Wiley-Liss,
Inc.
PMID- 29345815
TI - In search of cellular control: Signal transduction in context.
AB - The field of molecular cell biology has experienced enormous advances over the
last century by reducing the complexity of living cells into simpler molecular
components and binding interactions that are amenable to rigorous biochemical
analysis. However, as our tools become more powerful, there is a tendency to
define mechanisms by what we can measure. The field is currently dominated by
efforts to identify the key molecules and sequences that mediate the function of
critical receptors, signal transducers, and molecular switches. Unfortunately,
these conventional experimental approaches ignore the importance of
supramolecular control mechanisms that play a critical role in cellular
regulation. Thus, the significance of individual molecular constituents cannot be
fully understood when studied in isolation because their function may vary
depending on their context within the structural complexity of the living cell.
These higher-order regulatory mechanisms are based on the cell's use of a form of
solid-state biochemistry in which molecular components that mediate biochemical
processing and signal transduction are immobilized on insoluble cytoskeletal
scaffolds in the cytoplasm and nucleus. Key to the understanding of this form of
cellular regulation is the realization that chemistry is structure and hence,
recognition of the importance of architecture and mechanics for signal
integration and biochemical control. Recent work that has unified chemical and
mechanical signaling pathways provides a glimpse of how this form of higher-order
cellular control may function and where paths may lie in the future. J. Cell.
Biochem. Suppls. 30/31:232-237, 1998. (c) 1998 Wiley-Liss, Inc.
PMID- 29345816
TI - Initiation of DNA replication in eukaryotic chromosomes.
AB - Our understanding of the process by which eukaryotes regulate initiation of DNA
replication has made remarkable advances in the past few years, thanks in large
part to the explosion of genetic and biochemical information on the budding
yeast, Saccharomyces cerevisiae. At least three major concepts have emerged: 1)
The sequence of molecular events that determines when replication begins and how
frequently each replication site is used are conserved among most, if not all,
eukaryotes; 2) specific replication origins are used in most, if not all,
eukaryotes that consist of a flexible modular anatomy; and 3) epigenetic factors
such as chromatin structure and nuclear organization determine which of many
potential replication origins are used at different stages in animal development.
Thus, the current state of our knowledge suggests a simple unifying concept-all
eukaryotes utilize the same basic proteins and DNA sequences to initiate
replication, but the metazoa can change both the number and locations of
replication origins in response to the demands of animal development. J. Cell.
Biochem. Suppls. 30/31:8-17, 1998.
PMID- 29345817
TI - Intranuclear targeting of DNA replication factors.
AB - Mammalian nuclei are highly organized into functional compartments. Major nuclear
processes like DNA replication and RNA processing take place in distinct foci.
These microscopically visible foci are formed by the assembly of, for example,
DNA replication factors and associated proteins into megadalton complexes often
referred to as protein machines or factories. Thus far, two proteins, DNA ligase
I and DNA methyltransferase (DNA MTase), have been analyzed in greater detail. In
both cases, the assembly process appears to be controlled by distinct targeting
sequences that were attached to the catalytic protein core in the course of
evolution and mediate the association with replication factories in mammalian
cells. The dynamics of these nuclear structures throughout the cell cycle are
analyzed using green fluorescent protein (GFP). Further studies are needed to
elucidate the architecture, regulation, and role of these subnuclear structures.
J. Cell. Biochem. Suppls. 30/31:243-249, 1998. (c) 1998 Wiley-Liss, Inc.
PMID- 29345818
TI - Biomineralization: Conflicts, challenges, and opportunities.
AB - Biomineralization is the process by which mineral crystals are deposited in an
organized fashion in the matrix (either cellular or extracellular) of living
organisms. Over the past 25 years, new insights into the mechanisms that control
these processes have been obtained, yet questions asked then still persist,
especially in terms of vertebrate mineralization. Specifically, there are still
debates concerning the chemical nature of the first mineral crystals formed in
bone, dentin, and cementum; the factors leading to the initial deposition of
these crystals; and the functions of macromolecules found associated with these
crystals. In this review, emphasis is placed on the currently accepted answers to
these questions, drawing insight from nonvertebrate systems. It is suggested that
there are redundant calcification mechanisms and that, by taking advantage of our
current knowledge of these mechanisms, opportunities will be provided for
therapeutic manipulation of diseases in which biomineralization is impaired. J.
Cell. Biochem. Suppls. 30/31:83-91, 1998. (c) 1998 Wiley-Liss, Inc.
PMID- 29345819
TI - Steroid receptors at the nexus of transcriptional regulation.
AB - During the past few years, our understanding of nuclear receptor action has
dramatically improved as a result of the identification and functional analysis
of co-regulators such as factors involved in chromatin remodeling, transcription
intermediary factors (co-repressors and co-activators), and direct interactions
with the basal transcriptional machinery. Furthermore, the elucidation of the
crystal structures of the empty ligand-binding domains of the nuclear receptor
and of complexes formed by the nuclear receptor's ligand-binding domain bound to
agonists and antagonists has contributed significantly to our understanding of
the early events of nuclear receptor action. However, the picture of hormone- and
hormone receptor-mediated mechanisms of gene regulation remain incomplete and
extremely complicated when one also considers the "nontraditional" interactions
of hormone-activated nuclear receptors, for example, interactions between the
activated steroid receptors and components of the chromatin/nuclear matrix; and
finally the nongenomic effects that steroid hormones can exhibit with other
signaling pathways. In this prospectus on steroid receptors, we discuss the
implications of various steroid hormone and nuclear receptor interactions and
potential future directions of investigation. J. Cell. Biochem. Suppls. 30/31:185
193, 1998. (c) 1999 Wiley-Liss, Inc.
PMID- 29345820
TI - Marrow stromal cells as stem cells for continual renewal of nonhematopoietic
tissues and as potential vectors for gene therapy.
PMID- 29345821
TI - Oligosaccharide signaling of plant cells.
AB - A variety of oligosaccharide signals have been identified that function in the
regulation of plant development, defense, and other interactions of plants with
the environment. Some of these oligosaccharides are produced by various pathogens
or symbionts, whereas others are synthesized by the plant itself. This mini
review summarizes our present state of information on these oligosaccharide
signals and provides an overview of approaches being used to identify receptors
for these signals and gain an understanding of the mechanism(s) by which these
signals activate downstream events. Possible biotechnological applications of
future work in this field are also considered. J. Cell. Biochem. Suppls.
30/31:123-128, 1998. (c) 1998 Wiley-Liss, Inc.
PMID- 29345823
TI - Color section.
PMID- 29345822
TI - Linkages of nuclear architecture to biological and pathological control of gene
expression.
AB - Functional interrelationships between components of nuclear architecture and
control of gene expression are becoming increasingly evident. There is growing
appreciation that multiple levels of nuclear organization integrate the
regulatory cues that support activation and suppression of genes as well as the
processing of gene transcripts. The linear organization of genes and promoter
elements provide the potential for responsiveness to physiological regulatory
signals. Parameters of chromatin structure and nucleosome organization support
synergism between activities at independent regulatory sequences and render
promoter elements accessible or refractory to transcription factors. Association
of genes, transcription factors, and the machinery for transcript processing with
the nuclear matrix facilitates fidelity of gene expression within the three
dimensional context of nuclear architecture. Mechanisms must be defined that
couple nuclear morphology with enzymatic parameters of gene expression. The
recent characterization of factors that mediate chromatin remodeling and
intranuclear targeting signals that direct transcription factors to subnuclear
domains where gene expression occurs, reflect linkage of genetic and structural
components of transcriptional control. Nuclear reorganization and aberrant
intranuclear trafficking of transcription factors for developmental and tissue
specific control that occurs in tumor cells and in neurological disorders
provides a basis for high resolution diagnostics and targeted therapy. J. Cell.
Biochem. Suppls. 30/31:220-231, 1998. (c) 1998 Wiley-Liss, Inc.
PMID- 29345824
TI - The S phase: Beginning, middle, and end: A perspective.
AB - Events in the S phase of the cell cycle have been investigated to a relatively
limited extent in comparison with those in G1 and M phases. Four aspects of S are
briefly discussed in this report: (1) the final biochemical step permitting
initiation of DNA synthesis, (2) determination of replication timing of
individual genes and its mechanism, (3) S phase processes that lead to the onset
of M phase, and (4) resetting the S-phase machinery. J. Cell. Biochem. Suppls.
30/31:1-7, 1998. (c) 1999 Wiley-Liss, Inc.
PMID- 29345825
TI - Bone stem cells.
AB - Osteoblasts are the skeletal cells responsible for synthesis, deposition, and
mineralization of the extracellular matrix of bone. By mechanisms that are only
beginning to be understood, stem and primitive osteoprogenitors and related
mesenchymal precursors arise in the embryo and at least some appear to persist in
the adult organism, where they contribute to replacement of osteoblasts in bone
turnover and in fracture healing. In this paper, the nature of these cells,
whether they constitute a stem cell pool or a committed progenitor pool, and
aspects of their apparent plasticity are discussed. Current understanding of
differential expression of osteoblast-associated genes during osteoprogenitor
proliferation and differentiation to mature matrix synthesizing osteoblasts is
summarized. Finally, evidence is discussed that supports the hypothesis that the
mature osteoblast phenotype is heterogeneous with subpopulations of osteoblasts
expressing only subsets of the known osteoblast markers, raising also the
possibility of multiple parallel differentiation pathways and perhaps even
different progenitor pools. J. Cell. Biochem. Suppls. 30/31:73-82, 1998. (c) 1998
Wiley-Liss, Inc.
PMID- 29345826
TI - Nucleosome and chromatin structures and functions.
PMID- 29345827
TI - The ongoing saga of osteoporosis treatment.
PMID- 29345828
TI - Signal transduction by transforming growth factor-beta: A cooperative paradigm
with extensive negative regulation.
AB - Transforming growth factor-beta (TGF-beta) represents an evolutionarily conserved
family of secreted factors that mobilize a complex signaling network to control
cell fate by regulating proliferation, differentiation, motility, adhesion, and
apoptosis. TGF-beta promotes the assembly of a cell surface receptor complex
composed of type I (TbetaRI) and type II (TbetaRII) receptor serine/threonine
kinases. In response to TGF-beta binding, TbetaRII recruits and activates TbetaRI
through phosphorylation of the regulatory GS-domain. Activated TbetaRI then
initiates cytoplasmic signaling pathways to produce cellular responses. SMAD
proteins together constitute a unique signaling pathway with key roles in signal
transduction by TGF-beta and related factors. Pathway-restricted SMADs are
phosphorylated and activated by type I receptors in response to stimulation by
ligand. Once activated, pathway-restricted SMADs oligomerize with the common
mediator Smad4 and subsequently translocate to the nucleus. Genetic analysis in
Drosophila melanogaster and Caenorhabditis elegans, as well as TbetaRII and SMAD
mutations in human tumors, emphasizes their importance in TGF-beta signaling.
Mounting evidence indicates that SMADs cooperate with ubiquitous cytoplasmic
signaling cascades and nuclear factors to produce the full spectrum of TGF-beta
responses. Operating independently, these ubiquitous elements may influence the
nature of cellular responses to TGF-beta. Additionally, a variety of regulatory
schemes contribute temporal and/or spatial restriction to TGF-beta responses.
This report reviews our current understanding of TGF-beta signal transduction and
considers the importance of a cooperative signaling paradigm to TGF-beta-mediated
biological responses. J. Cell. Biochem. Suppls. 30/31:111-122, 1998. (c) 1998
Wiley-Liss, Inc.
PMID- 29345829
TI - Macromolecular exchanges between the nucleus and cytoplasm.
AB - The control of transcription and translation is of fundamental importance in cell
biology. In this regard, the nuclear envelope is in a unique position to
contribute to the regulation of these events, by directing macromolecular
exchanges between the nucleus and cytoplasm. Such exchanges occur through the
nuclear pore complexes, mainly by signal-mediated processes. Different signals
are required for import and export. Specific cytoplasmic or nuclear receptors
initially bind the signal-containing substrate, and the complex subsequently
interacts with the pores. Additional factors then assist in translocation across
the envelope. Current research is focused mainly on further characterization of
transport receptors, translocation factors, as well as components of the nuclear
pore complex, i.e., the nucleoporins. The ultimate goal is to understand the
molecular interactions that occur among the different components of the transport
apparatus, the energy sources for transport, and how variations in transport
capacity are generated. J. Cell. Biochem. Suppls. 30/31:214-219, 1998. (c) 1998
Wiley-Liss, Inc.
PMID- 29345830
TI - DNA vaccines: Vector design, delivery, and antigen presentation.
AB - Inoculations with antigen-expressing plasmid DNAs (DNA vaccines) in the
production of protective immune responses. Since the initial development of DNA
vaccines more than 5 years ago, major strides have been made in the design of
efficient vaccine vectors and in the process of vaccine delivery. However, many
questions remain regarding the mechanism of cellular transfection and in the
development of immune responses. This review addresses functional aspects of DNA
vaccines, including vector design and delivery, as well as cellular transfection
and antigen presentation. J. Cell. Biochem. Suppls. 30/31:304-311, 1998. (c) 1998
Wiley-Liss, Inc.
PMID- 29345831
TI - Signaling mechanisms and molecular characteristics of G protein-coupled receptors
for lysophosphatidic acid and sphingosine 1-phosphate.
AB - Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are potent
phospholipid mediators with diverse biological activities. Their appearance and
functional properties suggest possible roles in development, wound healing, and
tissue regeneration. The growth-stimulating and other complex biological
activities of LPA and S1P are attributable in part to the activation of multiple
G protein-mediated intracellular signaling pathways. Several heterotrimeric G
proteins, as well as Ras- and Rho-dependent pathways play central roles in the
cellular responses to LPA and S1P. Recently, several G protein-coupled receptors
encoded by a family of endothelial differentiation genes (edg) have been shown to
bind LPA or S1P and transduce responses of cAMP, Ca2+ , MAP kinases, Rho, and
gene transcription. This review summarizes our current understanding of signaling
pathways critical for cellular responses to LPA and S1P and of recent progress in
the molecular biological analyses of the Edg receptors. J. Cell. Biochem. Suppls.
30/31:147-157, 1998. (c) 1998 Wiley-Liss, Inc.
PMID- 29345832
TI - Introduction.
PMID- 29345833
TI - Osteocalcin gene promoter: Unlocking the secrets for regulation of osteoblast
growth and differentiation.
AB - The bone tissue-specific osteocalcin gene remains one of a few genes that
exhibits osteoblast-restricted expression. Over the last decade, characterization
of the promoter regulatory elements and complexes of factors that control
suppression of the osteocalcin gene in osteoprogenitor cells and transactivation
in mature osteoblasts has revealed transcriptional regulatory mechanisms that
mediate development of the osteoblast phenotype. In this review, we have focused
on emerging concepts related to molecular mechanisms supporting osteoblast growth
and differentiation based on the discoveries that the osteocalcin gene is
regulated by homeodomain factors, AP-1 related proteins, and the bone restricted
Cbfa1/AML3 transcription factor. J. Cell. Biochem. Suppls. 30/31:62-72, 1998. (c)
1998 Wiley-Liss, Inc.
PMID- 29345834
TI - A role for cadherins in cellular signaling and differentiation.
AB - Cadherins form a family of cell-cell adhesion proteins that are critical to
normal embryonic development. Expression of the various family members is
regulated in a complex pattern during embryogenesis. Both reduced and
inappropriate expression of cadherins have been associated with abnormal tissue
formation in embryos and tumorigenesis in mature organisms. Evidence is
accumulating that signals unique to individual members of the cadherin family, as
well as signals common to multiple cadherins, contribute to the differentiated
phenotype of various cell types. While a complete understanding of the regulation
of cadherin expression of the molecular nature of intracellular signaling
downstream of cadherin adhesion is essential to an understanding of embryogenesis
and tumorigenesis, our knowledge in both areas is inadequate. Clearly,
elucidating the factors and conditions that regulate cadherin expression and
defining the signaling pathways activated by cadherins are frontiers for future
research. J. Cell. Biochem. Suppls. 30/31:168-176, 1998. (c) 1998 Wiley-Liss,
Inc.
PMID- 29345835
TI - Translocations, fusion genes, and acute leukemia.
AB - Genes involved in chromosomal translocations, associated with the formation of
fusion proteins in leukemia, are modular in nature and regulatory in function. It
is likely that they are involved in the initiation and maintenance of normal
hematopoiesis. A conceptual model is proposed by which disruption of these
different genes leads to the development of acute leukemia. Central to this model
is the functional interaction between the mammalian trithorax and polycomb group
protein complexes. Many of the genes identified in leukemia-associated
translocations are likely upstream regulators, co-participators or downstream
targets of these complexes. In the natural state, these proteins interact with
each other to form multimeric higher-order structures, which sequentially
regulate the development of the normal hematopoietic state, either through HOX
gene expression or other less defined pathways. The novel interaction domains
acquired by the chimaeric fusion products subvert normal cellular control
mechanisms, which result in both a failure of cell maturation and activation of
anti-apoptotic pathways. The mechanisms by which these translocation products are
able to affect these processes are thought to lie at the level of chromatin
mediated transcriptional activation and/or repression. The stimuli for
proliferation and development of clinically overt disease may require subsequent
mutations in more than one oncogene or tumor suppressor gene, or both. A more
comprehensive catalogue of mutation events in malignant cells is therefore
required to understand the key regulatory networks that serve to maintain
multipotentiality and in particular the modifications which initiate and
coordinate commitment in differentiating hematopoietic cells. We propose a model
in which common pathways for leukemogenesis lie along the cell cycle control of
chromatin structure in terms of transcriptional activation or repression. A
clearer understanding of this cascade will provide opportunities for the design
and construction of novel biological agents that are able to restore normal
regulatory mechanisms. J. Cell. Biochem. Suppls. 30/31:264-276, 1998. (c) 1998
Wiley-Liss, Inc.
PMID- 29345836
TI - Regulation of intracellular membrane interactions: Recent progress in the field
of neurotransmitter release.
AB - Maintenance of compartmental independence and diversity is part of the blueprint
of the eukaryotic cell. The molecular composition of every organelle membrane is
custom tailored to fulfill its unique tasks. It is retained by strict sorting and
directional transport of newly synthesized cellular components by the use of
specific transport vesicles. Temporally and spatially controlled membrane fission
and fusion steps thus represent the basic process for delivery of both, membrane
bound and soluble components to their appropriate destination. This process is
fundamental to cell growth, organelle inheritance during cell division, uptake
and intracellular transport of membrane-bound and soluble molecules, and neuronal
communication. The latter process has become one of the best studied examples in
terms of regulatory mechanisms of membrane interactions. It has been dissected
into the stages of transmitter vesicle docking, priming, and fusion: Specificity
of membrane interactions depends on interactions between sets of organelle
specific membrane proteins. Priming of the secretory apparatus is an ATP
dependent process involving proteins and membrane phospholipids. Release of
vesicle content is triggered by a rise in intracellular free Ca2+ levels that
relieves a block previously established between the membranes poised to fuse.
Neurotransmitter release is a paradigm of highly regulated intracellular membrane
interaction and molecular mechanisms for this phenomenon begin to be delineated.
J. Cell. Biochem. Suppls. 30/31:103-110, 1998. (c) 1998 Wiley-Liss, Inc.
PMID- 29345837
TI - Regulation and regulatory parameters of histone modifications.
AB - Histone acetylation and phosphorylation destablizes nucleosome and chromatin
structure. Relaxation of the chromatin fiber facilitates transcription.
Coactivator complexes with histone acetyltransferase activity are recruited by
transcription factors bound to enhancers or promoters. The recruited histone
acetyltransferases may acetylate histone or nonhistone chromosomal proteins,
resulting in the relaxation of chromatin structure. Alternatively, repressors
recruit corepressor complexes with histone deacetylase activity, leading to
condensation of chromatin.This review highlights the recent advances made in our
understanding of the roles of histone acetyltransferases, histone deacetylases,
histone kinases, and protein phosphatases in transcriptional activation and
repression. Exciting reports revealing mechanistic connections between histone
modifying activities and the RNA polymerase II machinery, the coupling of histone
deacetylation and DNA methylation, the possible involvement of histone
deacetylases in the organization of nuclear DNA, and the role of chromatin
modulators in oncogenesis are discussed. J. Cell. Biochem. Suppls. 30/31:203-213,
1998. (c) 1998 Wiley-Liss, Inc.
PMID- 29345838
TI - Tissue engineering: The first decade and beyond.
AB - This article reviews the important developments in the field of tissue
engineering over the last 10 years. Research in the area of biomaterials is
examined from the perspective of providing the foundation for the development of
tissue engineering. Early efforts combining cells with biocompatible materials
are described and applications of this technology presented, with particular
focus on uses in orthopaedics and maxillofacial surgery. The basic principles of
tissue engineering and state-of-the-art technology in cell biology and materials
science as used currently in the field are presented. Finally, futures challenges
are outlined from the perspective of integrating technologies from medicine,
biology, and engineering, in hopes of translating tissue engineering to clinical
applications. J. Cell. Biochem. Suppls. 30/31:297-303, 1998. (c) 1998 Wiley-Liss,
Inc.
PMID- 29345839
TI - G-protein regulatory pathways: Rocketing into the twenty-first century.
AB - Complex cellular responses involve the integration of heterotrimeric G protein
systems with protein kinase signal transduction pathways. Key in this integration
is the control of small GTP-binding proteins including Ras and Rho family
members. In this paper, we discuss the control of signal transduction pathways by
G proteins and their integration with specific tyrosine kinases. The integration
of G proteins, kinases, and small GTP-binding proteins in controlling cellular
responses is illustrated through the newly defined Galpha12/13 -regulated
pathways. Furthermore, the polymorphonuclear leukocyte provides a primary cell
system for analyzing the integration of G proteins, kinases, and small GTP
binding proteins in controlling cellular functions such as superoxide production,
adherence, chemotaxis, and granule secretion. J. Cell. Biochem. Suppls. 30/31:137
146, 1998. (c) 1998 Wiley-Liss, Inc.
PMID- 29345840
TI - The new paradigm: Integrating genomic function and nuclear architecture.
AB - A new view of the cell nucleus is emerging based on the functional dynamics of
nuclear architecture. The striking structural preservation of a variety of
genomic processes on the nuclear matrix provides an important approach for
correlating nuclear form and function. In situ labeling coupled with three
dimensional microscopy and computer imaging techniques shows that DNA replication
and transcription sites are organized into higher-order units, or "zones," in the
cell nucleus. The dynamic interplay and "re-zoning" of replication and
transcription regions during the cell cycle may form the structural basis for the
elaborate global coordination of replicational and transcriptional programs in
the mammalian cell. J. Cell. Biochem. Suppls. 30/31:238-242, 1998. (c) 1998 Wiley
Liss, Inc.
PMID- 29345841
TI - Effects of high-impact exercise on the physical properties of bones of
ovariectomized rats fed to a high-protein diet.
AB - The aim of this study was to evaluate the effects of high-impact physical
exercise as a prophylactic and therapeutic means in osteopenic bones of rats
submitted to ovariectomy and protein diet intake. A total of 64 Wistar rats were
divided into eight groups (n = 8 each), being: OVX, ovx, standard diet and
sedentary; OVXE, ovx, standard diet and jump; OVXP, ovx, high-protein diet and
sedentary; and OVXEP, ovx, high-protein diet and jump; SH, sham, standard diet
and sedentary; SHE, sham, standard diet and jump; SHP, sham, high-protein diet
and sedentary; and SHEP, sham, high-protein diet and jump. OVX surgery consists
of ovariectomy, and sham was the control surgery. The jumping protocol consisted
of 20 jumps/day, 5 days/week. The bone structure was evaluated by densitometry,
mechanical tests, histomorphometric, and immunohistochemical analyses. A high
protein diet resulted in increased bone mineral density (P = .049), but decreased
maximal load (P = .026) and bone volume fraction (P = .023). The benefits of
physical exercise were demonstrated by higher values of the maximal load in the
trained groups compared to the sedentary groups (P < .001). The sham groups had
decreased immunostaining of osteocalcin (P = .004) and osteopontin (P = .010)
compared to ovx groups. However, the high-protein diet (P = .005) and jump
exercise (P = .017) resulted in lower immunostaining of osteopontin compared to
the standard diet and sedentary groups, respectively. In this experimental model,
it was concluded that ovariectomy and a high-fat diet can negatively affect bone
tissue and the high-impact exercise was not enough to suppress the deleterious
effects caused by the protein diet and ovariectomy.
PMID- 29345843
TI - Does the Use of Epiduroscopic Lysis of Adhesions Reduce the Need for Spinal Cord
Stimulation in Failed Back Surgery Syndrome? A Short-Term Pilot Study.
AB - BACKGROUND AND AIMS: Persistent low back pain after initially successful surgery
that is not attributed to structural deficits is called failed back surgery
syndrome (FBSS). When conservative and minimal invasive therapy fail, the
recommended treatment is spinal cord stimulation (SCS). Because epidural fibrosis
can be a contributing factor in the majority of FBSS patients, lumbosacral
epiduroscopic lysis of adhesions may be considered as a less invasive alternative
treatment option. We hypothesized that the use of epiduroscopic lysis of
adhesions could reduce the need for SCS. METHODS: A pilot study was performed in
35 consecutive patients with FBSS who underwent epiduroscopic lysis of adhesions.
SCS was considered if epiduroscopic lysis of adhesions gave less than 50% global
perceived effect (GPE) improvement after 15 months of follow-up. The GPE was
measured 1 week and 6 months after the procedure. RESULTS: Over a period of 69
months, 35 patients were included. After 15 months of follow-up, 43% of patients
required SCS. Eight of the 15 patients who reported no short-term improvement
needed SCS; those patients had severe epidural fibrosis. One week after
epiduroscopic lysis of adhesions, 34%, 23%, and 43% of patients reported GPE
improvement of > 50%, 20% to 50%, and < 20%, respectively. After 6 months, 5
patients were lost to follow-up, and 30%, 17%, and 16% of patients reported
improvement of > 50%, 20% to 50%, and < 20%, respectively. CONCLUSIONS: In this
pilot study we observed a reduced need for SCS when lumbosacral epiduroscopic
lysis of adhesions was used for patients with FBSS and magnetic resonance imaging
proven adhesions. These observations justify the evaluation of both treatment
options in a prospective observational trial.
PMID- 29345842
TI - Programmed death-ligand 1 is a promising blood marker for predicting tumor
progression and prognosis in patients with gastric cancer.
AB - Immune checkpoint inhibitor therapy has been clinically introduced for several
malignancies, and its effectiveness has been confirmed by clinical trials. In
particular, programmed cell death protein 1 (PD-1) and programmed death-ligand 1
(PD-L1) are widely known as important immune checkpoint molecules associated with
the mechanisms of immune escape by malignant tumor cells. In addition, liquid
biopsy of blood specimens has the clinical benefit of providing a simple,
repeatable sampling tool. Non-invasive liquid biopsy has recently been
spotlighted as a promising approach to predicting tumor progression and
prognosis. This study assessed the clinical significance of PD-L1 mRNA expression
in blood specimens obtained from patients with gastric cancer. Peripheral blood
specimens were collected before treatment from 124 patients with gastric cancer.
The PD-L1 mRNA expression was evaluated by quantitative RT-PCR. Programmed death
ligand 1 mRNA expression was significantly higher in patients with advanced
gastric cancer than in patients with early gastric cancer (P = .002). Moreover,
PD-L1 expression correlated significantly with depth of tumor invasion, distant
metastasis, and stage (P = .001, P < .001, and P < .001, respectively). Patients
with high PD-L1 expression showed significantly poorer prognosis than those with
low PD-L1 expression (P < .0001). Multivariate analysis indicated PD-L1
expression as an independent prognostic factor. Expression of PD-L1 in peripheral
blood may offer an immunological predictor of tumor progression and disease
outcome in patients with gastric cancer.
PMID- 29345844
TI - Assessing hepatitis C spontaneous clearance and understanding associated factors
A systematic review and meta-analysis.
AB - New advances in the treatment of hepatitis C provide high levels of sustained
viral response but their expense limits availability in publicly funded health
systems. The aim of this review was to estimate the proportion of patients who
will spontaneously clear HCV, to identify factors that are associated with
clearance and to support better targeting of directly acting antivirals. We
searched Ovid EMBASE, Ovid MEDLINE and PubMed from 1 January 1994 to 30 June 2015
for studies reporting hepatitis C spontaneous clearance and/or demographic,
clinical and behavioural factors associated with clearance. We undertook meta
analyses to estimate the odds of clearance for each predictor. Forty-three
studies met the inclusion criteria, representing 20 110 individuals, and 6 of
these studies included sufficient data to estimate spontaneous clearance. The
proportion achieving clearance within 3, 6, 12 and 24 months following infection
were, respectively, 19.8% (95% CI: 2.6%-47.5%), 27.9% (95% CI: 17.2%-41.8%),
36.1% (95% CI: 23.5%-50.9%) and 37.1% (95% CI: 23.7%-52.8%). Individuals who had
not spontaneously cleared by 12 months were unlikely to do so. The likelihood of
spontaneous clearance was lower in males and individuals with HIV co-infection,
the absence of HBV co-infection, asymptomatic infection, black or nonindigenous
race, nongenotype 1 infection, older age and alcohol or drug problems. This study
suggests that patients continue to spontaneously clear HCV for at least 12 months
following initial infection. However, injecting drug users are comparatively less
likely to achieve clearance; thus, they should be considered a priority for early
treatment given the continuing risks that these individuals pose for onwards
transmission.
PMID- 29345845
TI - Atypical familial Mediterranean fever developed in a long-term hemodialysis
patient.
AB - Familial Mediterranean Fever (FMF) is usually an autosomal recessive
autoinflammatory disease characterized by recurrent attacks of fever and
serositis. FMF develops before the age of 20 years in 90% of patients. It has
intervals of 1 week to several years between attacks, which leads to renal
dysfunction-amyloidosis. We report a case of atypical FMF that developed in a
long-term hemodialysis patient. A 65-year-old Japanese female undergoing
hemodialysis for 32 years was referred to our hospital with a fever of unknown
origin (FUO) following cervical laminoplasty. The fever occurred as recurrent
attacks accompanied by oligoarthralgia of the left hip and knee. We suspected FMF
because of recurrent self-limited febrile attacks, although the patient showed
atypical clinical features such as late-onset and highly frequent attacks. After
receiving treatment, she achieved a complete response to colchicine. Therefore, a
diagnosis of FMF was made based on the Tel-Hashomer criteria, which was confirmed
by genetic testing. The case suggests that FMF may be of note in long-term
hemodialysis patients developing FUO.
PMID- 29345846
TI - Stable and Highly Efficient Electrochemical Production of Formic Acid from Carbon
Dioxide Using Diamond Electrodes.
AB - High faradaic efficiencies can be achieved in the production of formic acid
(HCOOH) by metal electrodes, such as Sn or Pb, in the electrochemical reduction
of carbon dioxide (CO2 ). However, the stability and environmental load in using
them are problematic. The electrochemical reduction of CO2 to HCOOH was
investigated in a flow cell using boron-doped diamond (BDD) electrodes. BDD
electrodes have superior electrochemical properties to metal electrodes, and,
moreover, are highly durable. The faradaic efficiency for the production of HCOOH
was as high as 94.7 %. Furthermore, the selectivity for the production of HCOOH
was more than 99 %. The rate of the production was increased to 473 MUmol m-2 s
1 at a current density of 15 mA cm-2 with a faradaic efficiency of 61 %. The
faradaic efficiency and the production rate are almost the same as or larger than
those achieved using Sn and Pb electrodes. Furthermore, the stability of the BDD
electrodes was confirmed by 24 h operation.
PMID- 29345847
TI - Characterizing the temporal evolution of the hepatitis C virus epidemic in
Pakistan.
AB - Pakistan has the second largest number of HCV infections in the world. We
assessed past, present and future levels and trends of the HCV epidemic in
Pakistan. An age-structured mathematical model was developed and analysed to
describe transmission dynamics over 1980-2050. The model was fitted to a
nationally representative survey and a comprehensive database of systematically
gathered HCV Ab prevalence data. HCV Ab and chronic infection prevalences peaked
at 5.3% and 3.9% in 2000 but were projected to decline to 4.3% and 3.2% by 2017,
3.4% and 2.6% by 2030 and 2.6% and 1.9% by 2050, respectively. The number of
chronically infected individuals was estimated at 6 663 906 in 2017 and was
projected to peak at 6 665 900 in 2018 and decline to 6 372 100 in 2030 and 5 131
500 in 2050. Annual number of new infections peaked at 346 740 in 1992 but was
projected to decline to 198 320 in 2017, 151 090 in 2030 and 98 120 in 2050.
Incidence rate per 100 000 person-year peaked at 343 in 1988 but was projected to
decline to 99 in 2017, 62 in 2030 and 36 in 2050. Prevalence and incidence varied
by age, and the majority of new infections occurred in the 20-39 age group.
Prevalence and incidence of HCV in Pakistan have been slowly declining for two
decades-Pakistan is enduring a large epidemic that will persist for decades if
not controlled. Nearly, 10% of global infections are in Pakistan, with about 200
000 additional infections every year. Rapid and mass scale-up of prevention and
treatment programmes are critically needed.
PMID- 29345848
TI - Economic evaluation of cognitive behavioral therapy and Internet-based guided
self-help for binge-eating disorder.
AB - OBJECTIVE: To determine the cost-effectiveness of individual face-to-face
cognitive behavioral therapy (CBT) compared to therapist guided Internet-based
self-help (GSH-I) in overweight or obese adults with binge-eating disorder (BED).
METHOD: Analysis was conducted alongside the multicenter randomized controlled
INTERBED trial. CBT (n = 76) consisted of up to 20 individual therapy sessions
over 4 months. GSH-I (n = 71) consisted of 11 modules combining behavioral
interventions, exercises including a self-monitoring food diary, psychoeducation,
and 2 face-to-face coaching sessions over 4 months. Assessments at baseline,
after 4 months (post-treatment), as well as 6 and 18 months after the end of
treatment included health care utilization and sick leave days to calculate
direct and indirect costs. Binge-free days (BFD) were calculated as effect
measure based on the German version of the Eating Disorder Examination. The
incremental cost-effectiveness ratio (ICER) was determined, and net benefit
regressions, adjusted for comorbidities and baseline differences, were used to
derive cost-effectiveness acceptability curves. RESULTS: After controlling for
baseline differences, CBT was associated with non-significantly more costs
(+?2,539) and BFDs (+40.1) compared with GSH-I during the 22-month observation
period, resulting in an adjusted ICER of ?63 per additional BFD. CBTs probability
of being cost-effective increased above 80% only if societal willingness to pay
(WTP) was >=?250 per BFD. DISCUSSION: We did not find clear evidence for one of
the treatments being more cost-effective. CBT tends to be more effective but also
more costly. If the societal WTP for an additional BFD is low, then our results
suggest that GSH-I should rather be adopted.
PMID- 29345849
TI - Impact of cone beam computed tomography on periapical assessment and treatment
planning five to eleven years after surgical endodontic retreatment.
AB - AIM: To evaluate how additional information from Cone Beam CT (CBCT) impacts on
periapical assessment and treatment planning based on clinical examination and
periapical radiographs (PR) in cases followed up five to eleven years after
surgical endodontic retreatment (SER). METHODOLOGY: Patients receiving SER during
2004-2010 were reinvited for follow-up examination including clinical
examination, PR, and CBCT. In total, 108 patients (119 teeth) were reinvited, 74
patients (83 teeth) accepted to participate. Three observers initially assessed
PR according to the four-scaled, increasing disease severity criteria by Rud et
al. (International Journal of Oral Surgery, 1, 1972 and 195) and Molven et al.
(International Journal of Oral and Maxillofacial Surgery, 16, and 432):
'Radiographic assessment A'. By including clinical information 'Treatment plan A'
was made as follows: 1) no treatment, 2) further observation, 3) SER reoperation
(SER-R), or 4) extraction. Hereafter, the CBCT volume was assessed and the
information incorporated for 'Radiographic assessment B' followed by 'Treatment
plan B'. Agreement between radiographic assessments and between treatment plans
was recorded and assessed statistically by Stuart-Maxwell test for marginal
homogeneity. RESULTS: Nine teeth had been extracted; thus, the final analysis
included 74 teeth (66 patients). The radiographic assessment was changed as a
result of the CBCT evaluation in 38 cases (51.4%), of which 35 (47.3%) were to a
higher Rud & Molven score, P < 0.001. The treatment plan was changed for 18 teeth
(24.3%). For 14 teeth (18.9%), the change was from no treatment or further
observation to a more invasive treatment plan (SER-R or extraction), P = 0.005.
CONCLUSION: The use of CBCT for long-term follow-up after SER led to more cases
diagnosed with persisting or recurrent apical periodontitis and hence often to
the recommendation of a more invasive treatment modality.
PMID- 29345850
TI - Effects of glutaraldehyde-didecyldimethylammonium bromide combined disinfectant
on the cell surface of Staphylococcus aureus.
AB - AIMS: The effects of a new glutaraldehyde-didecyldimethylammonium bromide
combination disinfectant (GD) on the cell surface of Staphylococcus aureus, a
representative Gram-positive bacterium, were investigated in this study. METHODS
AND RESULTS: Results of bacterial surface structural analysis showed that GD
significantly changed the bacterial morphology. The membrane fluidity decreased
and outer membrane permeabilization increased after contact with GD. Furthermore,
the integrity of the cytoplasmic membrane was destroyed by over 99% after
exposure to GD for a short time. Bacterial ATPase activity correlated negatively
with the treatment of GD over time, and proteins were degraded. Assays of
intracellular component leakage indicated that GD caused the rapid leakage of K+
, Mg2+ , ATP molecules, and proteins into the extracellular environment.
CONCLUSIONS: The effects of GD against S. aureus are probably attributable to the
removal of the permeability barrier, changes in the S. aureus morphology, changes
in the structures and functions of the cell membrane, leakage of intracellular
substances and disturbance of the intracellular homeostasis. As a result, this
irreversible damage accelerated the death of S. aureus. SIGNIFICANCE AND IMPACT
OF THE STUDY: In an earlier study, the bactericidal mechanism of GD against
Escherichia coli was investigated. Hence, this study focused on the action of
mechanism of GD against S. aureus. It is important to clarify the disinfectant
bactericidal mechanisms of GD against bacterium, in general, and this study
provides theoretical support to the prevention of bacterial resistance.
PMID- 29345851
TI - The immunosuppressive effects of CD4+ CD25+ regulatory T cells on dendritic cells
in patients with chronic hepatitis B.
AB - The characteristics and functions of CD4+ CD25+ regulatory T cells (Tregs) have
been well defined in murine and human systems. However, the interaction or
crosstalk between CD4+ CD25+ Tregs and dendritic cells (DCs) remains
controversial. In this study, the effects of chronic hepatitis B (CHB) CD4+ CD25+
Tregs on the maturation and function of monocyte-derived DCs were examined. The
results showed that CD4+ CD25+ render the DCs inefficient as antigen-presenting
cells (APCs) despite prestimulation with CD40 ligand. This effect was marginally
reverted by applying neutralizing antibodies (Abs) to IL-10 and TGF-beta. There
were an increased IL-10 and TGF-beta secretion and reduced expression of
costimulatory molecules in DC. Thus, in addition to a direct suppressor effect on
CD4+ T cells, CD4+ CD25+ may modulate the immune response through DCs in CHB
patients.
PMID- 29345853
TI - Any Associations Between the Timing of the Peak QTc Prolongation, Depth of the
Admission T-Wave Inversions, and Extent/Intensity of Myocardial Edema in Patients
With Takotsubo Syndrome?
PMID- 29345852
TI - Cadmium and cadmium-tolerant soil bacteria in cacao crops from northeastern
Colombia.
AB - AIMS: This research aims to assess total-cadmium soil content and microbiological
aspects to understand the dynamics of culturable cadmium-tolerant bacteria (CdtB)
in cacao soils from northeastern Colombia. METHODS AND RESULTS: An integration of
inverted dish plating, Cd determination and a microcalorimetry assay (IMC) was
carried out. A farm in Boyaca showed the highest level of total soil Cd (3.74 mg
kg-1 ) followed by farms in Santander and Arauca (2.76 and 1.16 mg kg-1 ,
respectively). Coefficient of determination between total soil Cd and CFU of CdtB
was high (R2 = 0.83) for the farm in Boyaca. Moreover, a pool of 129 CdtB was
isolated, and phylogeny of 21 CdtB was discussed. Among CdtB strains isolated,
Enterobacter sp. CdDB41 showed major Cd immobilization capacity (Qmax of 2.21 and
2.32 J at 6 and 24 mg l-1 of CdCl2 ), with an immobilization rate of 0.220 mg kg
1 h-1 . CONCLUSIONS: Among CdtB strains isolated, Enterobacter sp. CdDB41 showed
major Cd immobilization capacity (Qmax of 2.21 and 2.32 J at 6 and 24 mg l-1 of
CdCl2 ), with an immobilization rate of 0.220 mg kg-1 h-1 . SIGNIFICANCE AND
IMPACT OF THE STUDY: Nothing is known about soil CdtB in cacao. Our data showed
that CdtB such as Enterobacter sp. has high immobilization capacity. Furthermore,
the otavite found in situ might be mineralized due to the bacterial metabolic
activity of CdtB.
PMID- 29345854
TI - [CH3 NH3 ]4 Ga4 SbS9 S0.28 O0.72 H: A Three-Dimensionally Open-Framework
Heterometallic Chalcogenidoantimonate Exhibiting Ni2+ Ion-Exchange Property.
AB - An open-framework chalcogenidoantimonate, namely, [CH3 NH3 ]4 Ga4 SbS9 S0.28
O0.72 H (1), has been solvothermally synthesized and structurally characterized.
Interestingly, 1 showed Ni2+ ion-exchange properties and wide pH resistance, with
a maximum exchange capacity of 76.9 mg g-1 . To the best of our knowledge, this
is the first example of amine-directed three-dimensional (3D) heterometallic
chalcogenidometalates for highly selective Ni2+ ion capture with a high
distribution coefficient (Kd =1.65*105 mL g-1 ).
PMID- 29345856
TI - Response to Teng et al.
PMID- 29345855
TI - Increased oestradiol in hepatitis E virus-infected pregnant women promotes viral
replication.
AB - Hepatitis E virus (HEV) infection causes subclinical diseases, leading to high
mortality (>25%) in pregnant women. HEV replication is aggressively escalated in
pregnant women, especially in the third trimester of pregnancy. Oestrogen plays
an important role in pregnancy. However, the pathogenesis of HEV in pregnant
women or immunosuppressive pregnant women (such as HIV-infected or organ
transplanted pregnant women) remains unclear. We investigated the role of
oestradiol in HEV infection in a cell culture system. HEV-infected pregnant women
had significantly higher oestradiol levels compared with uninfected individuals.
HEV infection was significantly increased in cells treated with analogues of
oestradiol, diethylstilbestrol (DES) or 17beta-oestradiol in a dose-dependent
way. However, tamoxifen, an antagonist oestrogen, inhibited HEV replication. HEV
infection inhibits oestrogen receptor (ER-alpha) expression. Immunofluorescence
and co-immunoprecipitation assays indicated that ER-alpha interacted with the
helicase of HEV ORF1 indirectly. More importantly, HEV infection was exacerbated
in immunosuppressive cells treated with an inhibitor of PI3K-AKT-mTOR signal
pathway (LY296004) and supplemented with pregnant women serum with high
oestradiol simultaneously. These results strongly suggest that pregnant women
with high oestradiol and/or immunosuppression will be vulnerable to HEV
infection.
PMID- 29345857
TI - News from the European Academy of Andrology (EAA).
PMID- 29345858
TI - Cardiopulmonary fitness is strongly associated with body cell mass and fat-free
mass: The Study of Health in Pomerania (SHIP).
AB - Peak oxygen uptake (VO2peak) is commonly indexed by total body weight (TBW) to
determine cardiopulmonary fitness (CPF). This approach may lead to
misinterpretation, particularly in obese subjects. We investigated the
normalization of VO2peak by different body composition markers. We analyzed
combined data of 3848 subjects (1914 women; 49.7%), aged 20-90, from two
independent cohorts of the population-based Study of Health in Pomerania (SHIP-2
and SHIP-TREND). VO2peak was assessed by cardiopulmonary exercise testing. Body
cell mass (BCM), fat-free mass (FFM), and fat mass (FM) were determined by
bioelectrical impedance analysis. The suitability of the different markers as a
normalization variable was evaluated by taking into account correlation
coefficients (r) and intercept (alpha-coefficient) values from linear regression
models. A combination of high r and low alpha values was considered as preferable
for normalization purposes. BCM was the best normalization variable for VO2peak
(r = .72; P <= .001; alpha-coefficient = 63.3 mL/min; 95% confidence interval
[CI]: 3.48-123) followed by FFM (r = .63; P <= .001; alpha-coefficient = 19.6
mL/min; 95% CI: -57.9-97.0). On the other hand, a much weaker correlation and a
markedly higher intercept were found for TBW (r = .42; P <= .001; alpha
coefficient = 579 mL/min; 95% CI: 483 to 675). Likewise, FM was also identified
as a poor normalization variable (r = .10; P <= .001; alpha-coefficient = 2133;
95% CI: 2074-2191). Sex-stratified analyses confirmed the above order for the
different normalization variables. Our results suggest that BCM, followed by FFM,
might be the most appropriate marker for the normalization of VO2peak when
comparing CPF between subjects with different body shape.
PMID- 29345859
TI - Development of a risk prediction model for lung cancer: The Japan Public Health
Center-based Prospective Study.
AB - Although the impact of tobacco consumption on the occurrence of lung cancer is
well-established, risk estimation could be improved by risk prediction models
that consider various smoking habits, such as quantity, duration, and time since
quitting. We constructed a risk prediction model using a population of 59 161
individuals from the Japan Public Health Center (JPHC) Study Cohort II. A
parametric survival model was used to assess the impact of age, gender, and
smoking-related factors (cumulative smoking intensity measured in pack-years, age
at initiation, and time since cessation). Ten-year cumulative probability of lung
cancer occurrence estimates were calculated with consideration of the competing
risk of death from other causes. Finally, the model was externally validated
using 47 501 individuals from JPHC Study Cohort I. A total of 1210 cases of lung
cancer occurred during 986 408 person-years of follow-up. We found a dose
dependent effect of tobacco consumption with hazard ratios for current smokers
ranging from 3.78 (2.00-7.16) for cumulative consumption <=15 pack-years to 15.80
(9.67-25.79) for >75 pack-years. Risk decreased with time since cessation. Ten
year cumulative probability of lung cancer occurrence estimates ranged from 0.04%
to 11.14% in men and 0.07% to 6.55% in women. The model showed good predictive
performance regarding discrimination (cross-validated c-index = 0.793) and
calibration (cross-validated chi2 = 6.60; P-value = .58). The model still showed
good discrimination in the external validation population (c-index = 0.772). In
conclusion, we developed a prediction model to estimate the probability of
developing lung cancer based on age, gender, and tobacco consumption. This model
appears useful in encouraging high-risk individuals to quit smoking and undergo
increased surveillance.
PMID- 29345860
TI - Reply to 'Mucosal ischemia and bowel gangrene can have different treatment
options in sigmoid volvulus'.
PMID- 29345862
TI - Thirty Great Years.
PMID- 29345861
TI - Ruthenium-Catalyzed Aerobic Oxidation of Amines.
AB - Amine oxidation is one of the fundamental reactions in organic synthesis as it
leads to a variety of value-added products such as oximes, nitriles, imines, and
amides among many others. These products comprise the key N-containing building
blocks in the modern chemical industry, and such transformations, when achieved
in the presence of molecular oxygen without using stoichiometric oxidants, are
much preferred as they circumvent the production of unwanted wastes. In parallel,
the versatility of ruthenium catalysts in various oxidative transformations is
well-documented. Herein, this review focuses on aerobic oxidation of amines
specifically by using ruthenium catalysts and highlights the major achievements
in this direction and challenges that still need to be addressed.
PMID- 29345863
TI - All Good Things....
PMID- 29345864
TI - Naltrexone and Disulfiram Treatment Response in Veterans With Alcohol Dependence
and Co-Occurring Problem-Gambling Features.
AB - BACKGROUND: Disordered gambling behavior frequently co-occurs with alcohol
dependence and other psychiatric conditions. Using data from a previously
published trial, we conducted secondary analyses to examine the influence of
problem-gambling features on treatment outcome for alcohol dependence or co
occurring psychopathology assessed via DSM-IV criteria. METHODS: Two hundred
fifty-four patients with alcohol dependence and co-occurring psychiatric
disorders were treated for 12 weeks in an outpatient medication study conducted
at 3 Veterans Administration outpatient clinics from October 1998 to March 2002.
Randomization included assignment to 1 of 4 groups: (1) naltrexone alone, (2)
placebo alone, (3) (open-label) disulfiram and (blinded) naltrexone, or (4) (open
label) disulfiram and (blinded) placebo. One hundred seventy-four participants
were evaluated for the diagnostic inclusionary criteria for pathological gambling
using the Massachusetts Gambling Screen. Primary outcome and secondary outcome
measures assessed alcohol use and psychiatric domains. RESULTS: Forty-five of 174
participants (25.9%) exhibited problem-gambling features (acknowledged 1 or more
inclusionary criteria for pathological gambling). A gambling-group-by-disulfiram
interaction was observed for abstinence, with problem-gambling features not
associated with beneficial response to disulfiram (z = 6.58, P = .01).
Participants with problem-gambling features reported significantly less
improvement over time in general psychiatric functioning (z = 2.62, P = .01),
specifically within somatization (z = 3.77, P < .01), phobic anxiety (z = 3.24, P
< .01), interpersonal sensitivity (z = 2.61, P = .01), paranoid ideation (z =
2.32, P = .02), and anxiety (z = 2.10, P = .04) domains. CONCLUSIONS: The
association between problem-gambling features and poorer outcomes in alcohol and
multiple nonsubstance psychiatric domains suggests the need for improved
screening for gambling problems in dually diagnosed populations and for the
development of empirically validated treatments for individuals with these
disorders.
PMID- 29345865
TI - The Few Who Served Deserved to Be Cared For.
PMID- 29345866
TI - Cognitive Impairment in Patients With Depression: Awareness, Assessment, and
Management.
AB - Cognitive impairment is a common, often persistent, symptom of major depressive
disorder (MDD) that is disproportionately represented in patients who have not
returned to full psychosocial functioning. The ultimate goal of treatment in
depression is full functional recovery, and assessing patients for cognitive
impairment and selecting treatments that address cognitive dysfunction should
lead to improved functional outcomes. Unfortunately, many clinicians use
screening and assessment tools that are not suited for measuring cognitive
impairment in patients with depression. The new THINC-it assessment tool is the
first instrument that provides objective and subjective data on dysfunction in
all the cognitive domains commonly affected by depression. In regard to
treatment, several pharmacologic and nonpharmacologic interventions have been
investigated as treatments for cognitive dysfunction in individuals with MDD.
However very few studies of treatments for cognitive function in patients with
MDD have been adequate, in terms of sample size and study methods, to guide
clinical practice. The best evidence supports the moderate efficacy of some
antidepressants, cognitive-behavioral therapy, and exercise. .
PMID- 29345867
TI - Findings of Interest.
PMID- 29345868
TI - The Gap Between the Randomized Controlled Trial-Based Evidence and Real-World
Practice in Switching Strategies of Major Depressive Disorder.
PMID- 29345869
TI - Drs Bschor and Baethge Reply.
PMID- 29345870
TI - Antidepressant Response and Dissociative Effects After Ketamine Treatment: Two
Sides of the Same Coin?
PMID- 29345871
TI - Dr Andrade Replies.
PMID- 29345872
TI - Cognitive Planning Neural Correlates in a Pediatric Monozygotic Twin Pair
Discordant for Obsessive-Compulsive Disorder: Exploring Potential Application in
Precision Medicine.
PMID- 29345874
TI - Epidemiology and Prevention of Tardive Dyskinesia.
AB - What risk factors suggest that patients are more likely to develop tardive
dyskinesia (TD)? Can TD symptoms be prevented? Read this CME activity to learn
about the prevalence, epidemiology, and prevention of these abnormal movements
from an expert.
PMID- 29345873
TI - Patient Education in Psychopharmacology and the Risk of Nocebo-Related Treatment
Inefficacy and Harm.
AB - Many studies have shown that educating patients about the potential adverse
effects of a drug can increase the chances that those adverse effects will be
experienced. Studies have further shown that how such information is communicated
can also impact this nocebo risk. Additionally, information provided through
patient education can influence treatment efficacy, perhaps by moderating the
placebo response. There is therefore a need to optimize the manner in which
patients are educated about their medications so that placebo-related benefits
are enhanced and nocebo-related harm is minimized. This article provides
suggestions on the subject for clinical practice as well as research. Nonspecific
factors in psychopharmacology are important and should not be neglected.
PMID- 29345875
TI - Available Tools for Assessing Cognitive Impairment in Major Depressive Disorder.
AB - You know that measuring cognition in your patients with depression is important.
But cognitive assessment instruments can be difficult to access, expensive, time
consuming, and not available in an electronic format. Read this CME activity to
learn about a new free tool.
PMID- 29345876
TI - Assessing Patients for Tardive Dyskinesia.
AB - Do you regularly screen for tardive dyskinesia in at-risk patients? Explore this
CME activity by a well-known expert for information on rating scales for
screening, available diagnostic criteria, assessment tips, and monitoring
recommendations.
PMID- 29345877
TI - Comparing Treatments for Tardive Dyskinesia.
AB - Many treatment interventions for tardive dyskinesia have been studied, but some
have better evidence than others. Read this CME activity to get an expert's
perspectives on the evidence for older and newer treatments so that you can
minimize abnormal movements in your patients.
PMID- 29345878
TI - Impact of Cognitive Impairment on Functioning in Patients With Depression.
AB - Reassessing a patient's diagnosis if he or she does not respond adequately to
initial antidepressant pharmacotherapy is imperative. In this CME activity,
evaluate the case of Melissa, a 32-year-old architect with a potential case of
treatment-resistant depression, and decide on appropriate treatment strategies.
PMID- 29345879
TI - Improving Long-Term Outcomes in Patients With Schizophrenia: What Is the Evidence
for Long-Acting Injectable Antipsychotics?
AB - Do you consider long-acting injectable (LAI) antipsychotics when selecting among
treatments for schizophrenia? Take part in this CME activity to review the
evidence for LAIs vs oral medications and to learn which patients may benefit
most from this treatment option. Plus, discover the pharmacokinetic properties of
LAIs and barriers to their use.
PMID- 29345880
TI - Strategies for Managing Patients With Depression Who Are Experiencing Cognitive
Impairment.
AB - Pronounced deficits in executive function are found in up to one-third of
patients with MDD, and this impairment can keep patients from achieving full
functional recovery. In this CME activity, review the evidence regarding the
effectiveness of available interventions to improve cognitive dysfunction in
patients with MDD.
PMID- 29345881
TI - Noninferiority Trials.
PMID- 29345882
TI - Improvement of Antitumor Efficacy by Combination of Thermosensitive Liposome with
High-Intensity Focused Ultrasound.
AB - High intensity focused ultrasound (HIFU), allowing for precise heating of the
deep and local area, is emerging as the source of mild hyperthermia for delivery
of doxorubicin (DOX) using thermosensitive liposomes (TSLs). Conventionally, HIFU
has been used for intravascular drug release at tumor tissue by inducing mild
hyperthermia immediately upon systemic administration of DOX-TSLs. This immediate
heating approach (IHA), however, limits the deep penetration of DOX for high
anticancer efficacy. In an attempt to maximize the accumulation of DOX at tumor,
the delayed heating approach (DHA) has been explored. In this approach, DOX-TSLs
were intravenously administered into the tumor-bearing mice after pre-treatment
of tumor tissue with HIFU to increase vascular permeability. We developed the
fatty acid-cojugated elastinlike polypeptide bearing TSL (FTSL). The DOX-loaded
FTSLs had a hydrodynamic size of 142 nm. In vivo biodistribution study
demonstrated that DOX-FTSLs were selectively accumulated at tumor tissue with the
maximum amount of DOX at 6 h post-injection. Thereafter, the tumor tissue was
heated to 42 degrees C to induce rapid release of DOX from FTSLs. The results
have demonstrated that, compared to IHA, DHA significantly enhances the antitumor
efficacy of DOX-FTSLs because of their effective penetration to tumor tissue via
the enhanced permeation retention effect, followed by rapid release of DOX.
PMID- 29345883
TI - Crisis in the Sustainability of the U.S. Blood System.
PMID- 29345884
TI - Crisis in the Sustainability of the U.S. Blood System.
PMID- 29345885
TI - Superparamagnetic Iron Oxide Nanorod Carriers for Paclitaxel Delivery in the
Treatment and Imaging of Colon Cancer in Mice.
AB - A multifunctional magnetic drug delivery system was developed and explored as an
efficient and less invasive technique to improve colon cancer diagnosis and
therapy in mice. In this system, superparamagnetic iron oxide nanorod cores
enhanced passive targeting by bandaging a magnet adjacent to the tumor site,
whereas pluronic F127 shell acted as the carrier for paclitaxel. The pluronic
conjugated superparamagnetic iron oxide cores were prepared using the
hydrothermal method. It was found that the initial pluronic concentration exerted
a significant effect on the distribution of the diameters and lengths of the
nanorods. Despite the variation in pluronic concentrations and dimensions of iron
oxide products, all the samples exhibited negligible coercivity and remanence,
confirming their superparamagnetic characteristics. The pluronic F127
superparamagnetic iron oxide nanocarriers were then prepared by encapsulation of
nanorods into pluronic micelles and assessed for paclitaxel loading. Results
showed that paclitaxel was incorporated into the core of the micelles through
hydrophobic interactions, and that elevating both paclitaxel concentration and
temperature increased the loading efficiency. The therapeutic effect of
paclitaxel-loaded nanocarriers was then tested in in vitro and in vivo colon
cancer models. Compared to docetaxel, the paclitaxel-loaded magnetic nanocarriers
significantly suppressed tumor growth and improved survival time of xenograft
mice. The accumulated magnetic nanocarriers inside the tumor also served as a
contrast agent and enhanced magnetic resonance imaging localization and
visualization of the small tumor.
PMID- 29345886
TI - Curcumin-Zein Nanospheres Improve Liver Targeting and Antifibrotic Activity of
Curcumin in Carbon Tetrachloride-Induced Mice Liver Fibrosis.
AB - Liver fibrosis is a major health problem that has no satisfactory medication.
Curcumin, (CUR) although known for its antifibrotic activity, has limited
medicinal use owing to its poor oral pharmacokinetic properties and targeting
efficiency. The current study aimed at exploring the ability of zein (ZN)
nanospheres to improve the liver targeting and antifibrotic activity of CUR in a
mouse model of carbon tetrachloride (CCl4)-induced liver fibrosis. Four different
formulae of ZN-loaded CUR were prepared and examined in terms of particle size,
zeta potential, encapsulation efficiency, and in vitro permeation. The formula
containing a CUR to ZN ratio of 1:3 showed optimum nanosphere properties and was
subjected to further investigations. Under a scanning electron microscope, the
selected formula showed spherical particles with uniform size distribution. In
normal mice, the selected formula exhibited improved bioavailability and liver
targeting efficiency compared to raw CUR. The nanosphere preparation also offered
significant protection against CCl4-induced liver function deterioration,
histopathological changes, and oxidative stress in mice. Compared to raw CUR, CUR
ZN was significantly more effective in attenuating the rise in hepatic gene
expression of collagen-1, tissue inhibitor of metalloproteinase-2, and
transforming growth factor beta, as well as the downregulation of matrix
metalloproteinase-2 expression. Masson's trichrome staining confirmed the higher
antifibrotic activity of the nanospheres that ameliorated the rise in hepatic
hydroxyproline content and collagen-1-immunopositive areas in mice liver
sections. In conclusion, CUR-ZN nanospheres demonstrated improved liver targeting
efficiency and antifibrotic activity in comparison to raw CUR in CCl4-induced
liver fibrosis in mice.
PMID- 29345887
TI - Nanotheranostic Based Iron Oxide (Fe3O4) Saturated Lactoferrin Nanocapsules for
Colonic Adenocarcinoma.
AB - Efficient early detection of cancer and its simultaneous therapy can improve the
survival of cancer patients significantly. Recently there is great interest for
the development of nanotheranostic systems with multimodal live real-time imaging
ability. Novel multimodal multifunctional iron oxide (Fe3O4) saturated
lactoferrin (FebLf) nanocapsules/nanocarriers (FebLf NCs) nanoformulation was
fabricated. Anti-cancer nanotheranostic ability in human xenograft colonic
adenocarcinoma model was conducted in vivo by employing near infrared
flouroscence (NIRF) real time live mice imaging technology. FebLf NCs showed
spherical morphology with 50 to 80 nm size with super paramagnetic property and
exhibited profound in vivo anti-tumour efficacy, leading to regression of the
xenograft colonic tumour growth over a 90 day trial period. NIRF real time
imaging revealed selective localisation patterns of the FebLf NCs at the tumour
site causing tumour growth inhibition. In turn, ex vivo NIRF imaging of mice
organs showed enhanced tumoural uptake and biodistribution at the vital organs
including spleen, intestine, kidney, and intestine. Low-density lipoprotein
receptors (LDLRs), ferroportin, ferritin receptor based in vivo internalisation
mechanisms and iron metabolism regulation were observed. Histopathological
analysis revealed obsolute non-toxic nature of FebLf NCs in mice tissues. These
observations summate biocompatible, multimodal anticancer activity of novel FebLf
NCs for real time cancer therapeutic imaging leading to targeted colonic
adenocarcinoma therapy.
PMID- 29345888
TI - Nanoparticles with Optimal Ratiometric Co-Delivery of Docetaxel with Gambogic
Acid for Treatment of Multidrug-Resistant Breast Cancer.
AB - It has been reported that gambogic acid (GA), the main active component of
gamboge, could directly inhibit and reduce the expression level of P-gp by
promoting protein degradation through post-translational proteasome pathway. In
this study, the optimal molar ratio of GA/docetaxel (DTX) that could recover the
sensitivity of MCF-7/ADR cells to DTX was firstly investigated. Then GA and DTX
were loaded simultaneously in PLGA nanoparticles in terms of the optimal ratio.
In vitro cell apoptosis and western-blot assays showed that co-delivery of
anticancer drugs resulted in enhanced cell apoptosis through the downregulation
of the expression level of P-gp. Interestingly, in vivo pharmacokinetic study
demonstrated that GA and DTX are released synchronously in blood from the NPs.
Finally, the most effective tumor growth inhibition in the MCF-7/ADR human breast
tumor xenograft was observed in the co-delivery nanoparticle formulation group in
comparison with saline control, free DTX solution and free DTX/GA solution. Taken
together, our study demonstrated that DTX/GA PLGA NPs based combination therapy
holds significant potential towards the treatment of multidrug-resistant breast
cancer.
PMID- 29345889
TI - Modulation of MicroRNAs 34a and 21 Affects Viability, Senescence, and Invasion in
Glioblastoma Multiforme.
AB - Glioblastoma multiforme (GBM) is an aggressive and invasive brain tumor. Current
interventional strategies have been minimally successful. Three key
characteristics of GBMs are (1) enhanced resistance to apoptosis, (2) increased
proliferation rate, and (3) increased invasion potential, making them difficult
to treat. MicroRNAs (miRs) have demonstrated beneficial therapeutic intervention;
particularly miRs 34a and 21, which have been implicated in regulation of
apoptosis, senescence, and invasion of GBM tumor cells. MiR21 is anti-apoptotic
and pro-proliferative, whereas miR34a is proapoptotic and an anti-invasive
regulator in tumor cells. Our study investigates the effects of modulating both
miR34a and miR21, in addition to comparing the two individual treatments. Using
targeted cationic liposomes that bind to the epidermal growth factor receptor
(EGFR), we delivered miR34a and/or anti-sense oligonucleotide to miR21 (ASO21) to
GBM tumor cell lines, U87MG and A172, in vitro. Our data demonstrate that co
delivery of miR34a and ASO21 results in enhanced reduction in viability and
invasion, while increasing senescence in vitro. Additionally, there were
significant decreases in pro-invasion and -proliferation gene markers, as well as
an increase in pro-apoptotic markers. In vivo results demonstrate that the
combination of miR34a and ASO21 reduced tumor volume and proliferation of the
A172 tumor cells. Accumulation of rhodamine encapsulated EGFR-targeted cationic
liposomes was observed throughout the primary tumor bed after systemic injection.
To our knowledge, we are the first to modulate multiple miRs, while using a
targeted cationic liposomal delivery for miR-based therapy. These results
demonstrate a potential clinically relevant, miR therapeutic strategy for GBM.
PMID- 29345890
TI - How Medicare Could Provide Dental, Vision, and Hearing Care for Beneficiaries.
AB - Issue: The Medicare program specifically excludes coverage of dental, vision, and
hearing services. As a result, many beneficiaries do not receive necessary care.
Those that do are subject to high out-of-pocket costs. Goal: Examine gaps in
access to dental, vision, and hearing services for Medicare beneficiaries and
design a voluntary dental, vision, and hearing benefit plan with cost estimates.
Methods: Uses the Medicare Current Beneficiary Survey, Cost and Use File, 2012,
with population and costs projected to 2016 values. Findings and Conclusions:
Among Medicare beneficiaries, 75 percent of people who needed a hearing aid did
not have one; 70 percent of people who had trouble eating because of their teeth
did not go to the dentist in the past year; and 43 percent of people who had
trouble seeing did not have an eye exam in the past year. Lack of access was
particularly acute for poor beneficiaries. Because few people have supplemental
insurance covering these additional services, among people who received care,
three-fourths of their costs of dental and hearing services and 60 percent of
their costs of vision services were paid out of pocket. We propose a basic
benefit package for dental, vision, and hearing services offered as a premium
financed voluntary insurance option under Medicare. Assuming the benefit package
could be offered for $25 per month, we estimate the total coverage costs would be
$1.924 billion per year, paid for by premiums. Subsidies to reach low-income
beneficiaries would follow the same design as the Part D subsidy.
PMID- 29345891
TI - Rapid and Sensitive Fusion Gene Detection in Prostate Cancer Urinary Specimens by
Label-Free Surface-enhanced Raman Scattering.
AB - Recurrent chromosomal rearrangements such as fusion genes are associated with
cancer initiation and progression. Prostate cancer (PCa) is a leading cause of
cancer-related deaths in men and the TMPRSS2-ERG gene fusion is a recurrent
biomarker in about 50% of all prostate cancers. However, current screening tools
for TMPRSS2-ERG are generally confined to research settings and hence, the
development of a rapid, sensitive and accurate assay for TMPRSS2-ERG detection
may aid in clinical PCa diagnosis and treatment. Herein, we described a new
strategy for non-invasive TMPRSS2-ERG detection in patient urinary samples by
coupling of isothermal reverse transcription-recombinase polymerization
amplification (RT-RPA) to amplify TMPRSS2-ERG transcripts and surface-enhanced
Raman scattering (SERS) to directly detect the amplicons. This novel coupling of
both techniques allows rapid and quantitative TMPRSS2-ERG detection. Our assay
can specifically detect as low as 103 copies input of TMPRSS2-ERG transcripts and
was successfully applied to clinical PCa urinary samples. Hence, we believe our
assay is a potential clinical screening tool for TMPRSS2-ERG in PCa and may have
broad applications in detecting other gene fusion transcripts in other diseases.
PMID- 29345892
TI - Colistin-Functionalized Nanoparticles for the Rapid Capture of Acinetobacter
baumannii.
AB - Gold nanoparticles (AuNPs) were functionalized for rapid binding of Acinetobacter
baumannii (A. baumannii), a Gram-negative bacterium. AuNPs were functionalized
with colistin (Col), a polycationic antibiotic, using a two-step self-assembly
process, in which heterobifunctional polyethylene glycol (PEG) was used as a
linker. Colistin was successfully conjugated to the AuNPs (Col-PEG-AuNP), as
validated by dynamic light scattering (DLS) and proton nuclear magnetic resonance
(H1 NMR). High angle annular dark field scanning transmission electron microscopy
(HAADF-STEM) images, acquired simultaneously with X-ray energy dispersive
spectroscopy (EDS) data, confirmed binding of Col-PEG-AuNPs to the cell envelope
of A. baumannii. Results generated from a binding assay indicated that Col-PEG
AuNP complexation with A. baumannii occurred rapidly and reached half-maximum
saturation in approximately 7 minutes, on average, for all A. baumannii strains
evaluated. Quantitative measurement of the kinetics of Col-PEG-AuNP binding to A.
baumannii is essential to inform the design of colistin-functionalized magnetic
nanoparticles for magnetic separation of nanoparticle-bound A. baumannii.
PMID- 29345893
TI - Fullerene C60 Derivatives Attenuated Microglia-Mediated Prion Peptide
Neurotoxicity.
AB - Prion disorders are progressive neurodegenerative diseases characterized by
extensive neuronal loss, which is linked to the extracellular accumulation of the
scrapie isoform (PrPSC) of the normal cellular prion protein (PrPC). As
microglial activation is a central event in pathogenesis of prion disease, the
strategies that reduce microglial activation may have therapeutic benefits. In
this study, the neuroprotective effects of hydroxylated C60(C60-OH) and amino
modified-C60(C60-NH2) were evaluated by using PrP(106-126)-stimulated BV-2 cells
as a model of activated microglia. Herein, we showed that microglial activation
in response to PrP(106-126) was effectively attenuated by pretreatment with C60
OH as compared with C60-NH2. C60-OH significantly inhibited the excessive
production of inflammatory mediators, such as prostaglandin E2 (PGE2), nitric
oxide (NO), tumor necrosis factors (TNF)-alpha, interleukin (IL)-1beta, and IL-6,
and blocked the expression of cyclooxygenase-2 (COX-2) and inducible nitric-oxide
synthase (iNOS) in PrP(106-126)-stimulated BV-2 cells. C60-OH exerted anti
inflammatory potential by up-regulating the expression of antioxidant enzymes via
activation of nuclear factor erythroid 2-related factor 2 (Nrf2). The inhibitory
effect of C60-OH against PrP(106-126)-induced inflammatory response was abolished
by siRNA of Nrf2. In addition, conditioned culture media taken from PrP(106-126)
stimulated microglia cause apoptotic neuronal cell death, which was suppressed by
pretreatment with C60-OH. Take together, these results suggest that C60-OH
protects neuronal cells against PrP(106-126)-mediated neurotoxicity through
activation of Nrf2 pathway, and provides evidence that fullerene derivatives may
have therapeutic potential in prion diseases.
PMID- 29345894
TI - High-Bandwidth White-Light System Combining a Micro-LED with Perovskite Quantum
Dots for Visible Light Communication.
AB - This work proposes a high-bandwidth white-light system consisting of a blue
gallium nitride (GaN) micro-LED (MULED) exciting yellow-emitting CsPbBr1.8I1.2
perovskite quantum dots (YQDs) for high-speed real-time visible light
communication (VLC). The packaged 80 MUm * 80 MUm blue-emitting MULED has a
modulation bandwidth of ~160 MHz and a peak emission wavelength of ~445 nm. The
achievable bandwidth of the white-light system is up to 85 MHz in the absence of
filters and equalization technology. Meanwhile, the bandwidth of the YQDs as a
color converter is as high as 73 MHz with the blue GaN MULED as the pump source.
A maximum data rate of 300 Mbps can be achieved by taking advantage of the high
bandwidth of the white-light system using the non-return-to-zero on-off keying
(NRZ-OOK) modulation scheme. The resultant bit-error rate is 2.0 * 10-3, well
beneath the forward error correction criterion of 3.8 * 10-3 required for error
free data transmission. In addition, the YQDs which we proposed as a color
converter possess high stability for VLC. After half a year, the achievable
bandwidths of the white-light system and the YQDs are still up to 83 and 70 MHz,
respectively. This study provides the direction of developing high-bandwidth
white-light system for both high-efficiency solid-state lighting and high-speed
VLC.
PMID- 29345895
TI - Selective Discrimination of Key Enzymes of Pathogenic and Nonpathogenic Bacteria
on Autonomously Reporting Shape-Encoded Hydrogel Patterns.
AB - This work reports on a new approach to rapidly and selectively detect and
discriminate enzymes of pathogenic from those of nonpathogenic bacteria using a
patterned autonomously reporting hydrogel on a transparent support, in which the
selectivity has been encoded by the pattern shape to enable facile detection by a
color change at one single wavelength. In particular, enzyme-responsive chitosan
hydrogel layers that report the presence of the enzymes beta-glucuronidase (beta
Gus) and beta-galactosidase (beta-Gal), produced by the nonvirulent Escherichia
coli K12 and the food-borne biosafety level 3 pathogen enterohemorrhagic E. coli,
respectively, via the blue color of an indigo dye were patterned by two
complementary strategies. The comparison of the functionalization of patterned
chitosan patches on a solid support with two chromogenic substrates on one hand
and the area-selective conjugation of the substrates on the other hand showed
that the two characteristic enzymes could indeed be rapidly and selectively
discriminated. The limits of detection of the highly stable sensing layers for an
observation time of 60 min using a spectrophotometer correspond to enzyme
concentrations of beta-Gus and beta-Gal of <=5 and <=3 nM, respectively, and to
<=62 and <=33 nM for bare eye detection in nonoptimized sensor patches. These
results confirm the applicability of this approach, which is compatible with the
simple measurement of optical density at one single wavelength only as well as
with parallel, multiplexed detection, to differentiate the enzymes secreted by a
highly pathogenic E. coli from a nonpathogenic E. coli on the basis of
specifically secreted enzymes. Hence, a general approach for the rapid and
selective detection of enzymes of different bacterial species for potential
applications in food safety as well as point-of-care microbiological diagnostics
is described.
PMID- 29345896
TI - Correction to Fingerprint Analysis: Moving Toward Multiattribute Determination
via Individual Markers.
PMID- 29345897
TI - Design, Synthesis, and Biological Evaluation of 1-Benzylamino-2-hydroxyalkyl
Derivatives as New Potential Disease-Modifying Multifunctional Anti-Alzheimer's
Agents.
AB - The multitarget approach is a promising paradigm in drug discovery, potentially
leading to new treatment options for complex disorders, such as Alzheimer's
disease. Herein, we present the discovery of a unique series of 1-benzylamino-2
hydroxyalkyl derivatives combining inhibitory activity against
butyrylcholinesterase, beta-secretase, beta-amyloid, and tau protein aggregation,
all related to mechanisms which underpin Alzheimer's disease. Notably,
diphenylpropylamine derivative 10 showed balanced activity against both disease
modifying targets, inhibition of beta-secretase (IC50 hBACE-1 = 41.60 MUM),
inhibition of amyloid beta aggregation (IC50 Abeta = 3.09 MUM), inhibition of tau
aggregation (55% at 10 MUM); as well as against symptomatic targets,
butyrylcholinesterase inhibition (IC50 hBuChE = 7.22 MUM). It might represent an
encouraging starting point for development of multifunctional disease-modifying
anti-Alzheimer's agents.
PMID- 29345898
TI - Engineered Phage Matrix Stiffness-Modulating Osteogenic Differentiation.
AB - Herein, we demonstrate an engineered phage mediated matrix for osteogenic
differentiation with controlled stiffness by cross-linking the engineered phage
displaying Arg-Gly-Asp (RGD) and His-Pro-Gln (HPQ) with various concentrations of
streptavidin or polymer, poly(diallyldimethylammonium)chloride (PDDA). Osteogenic
gene expressions showed that they were specifically increased when MC3T3 cells
were cultured on the stiffer phage matrix than the softer one. Our phage matrixes
can be easily functionalized using chemical/genetic engineering and used as a
stem cell tissue matrix stiffness platform for modulating differential cell
expansion and differentiation.
PMID- 29345899
TI - Three-Dimensional Graphene Foam-Polymer Composite with Superior Deicing
Efficiency and Strength.
AB - The adhesion of ice severely compromises the aerodynamic performance of aircrafts
operating under critically low-temperature conditions to their surfaces. In this
study, highly thermally and electrically conductive graphene foam (GrF) polymer
composite is fabricated. GrF-polydimethylsiloxane (PDMS) deicing composite
exhibits superior deicing efficiency of 477% and electrical conductivities of 500
S m-1 with only 0.1 vol % graphene foam addition as compared to other nanocarbon
based deicing systems. The three-dimensional interconnected architecture of GrF
allows the effective deicing of surfaces by employing low power densities (0.2 W
cm-2). Electrothermal stability of the GrF-PDMS composite was proven after
enduring 100 cycles of the dc loading-unloading current. Moreover,
multifunctional GrF-PDMS deicing composite provides simultaneous mechanical
reinforcement by the effective transfer and absorption of loads resulting in a
23% and 18% increase in elastic modulus and tensile strength, respectively, as
compared to pure PDMS. The enhanced efficiency of the GrF-PDMS deicing composite
is a novel alternative to current high-power consumption deicing systems.
PMID- 29345900
TI - High-Performance Ga2O3 Anode for Lithium-Ion Batteries.
AB - There is a great deal of interest in developing battery systems that can exhibit
self-healing behavior, thus enhancing cyclability and stability. Given that
gallium (Ga) is a metal that melts near room temperature, we wanted to test if it
could be employed as a self-healing anode material for lithium-ion batteries
(LIBs). However, Ga nanoparticles (NPs), when directly applied, tended to
aggregate upon charge/discharge cycling. To address this issue, we employed
carbon-coated Ga2O3 NPs as an alternative. By controlling the pH of the precursor
solution, highly dispersed and ultrafine Ga2O3 NPs, embedded in carbon shells,
could be synthesized through a hydrothermal carbonization method. The particle
size of the Ga2O3 NPs was 2.6 nm, with an extremely narrow size distribution, as
determined by high-resolution transmission electron microscopy and Brunauer
Emmett-Teller measurements. A lithium-ion battery anode based on this material
exhibited stable charging and discharging, with a capacity of 721 mAh/g after 200
cycles. The high cyclability is due to not only the protective effects of the
carbon shell but also the formation of Ga0 during the lithiation process, as
indicated by operando X-ray absorption near-edge spectroscopy.
PMID- 29345902
TI - Flexible Amoxicillin-Grafted Bacterial Cellulose Sponges for Wound Dressing: In
Vitro and in Vivo Evaluation.
AB - In this study, we report the design and fabrication of a novel biocompatible
sponge with excellent antibacterial property, making it a promising material for
wound dressings. The sponge is formed by grafting amoxicillin onto regenerated
bacterial cellulose (RBC). It was observed that the grafted RBC could enhance the
antibacterial activity against fungus, Gram-negative, and Gram-positive bacteria.
The morphology of strains treated with the grafted RBC and fluorescent stain
results further demonstrated the antibacterial ability of the fabricated sponge.
Moreover, a cytocompatibility test evaluated in vitro and in vivo illustrates the
nontoxicity of the prepared sponge. More importantly, the wound infection model
reveals that this sponge can accelerate the wound healing in vivo. This work
indicates the novel sponge has the huge potential in wound dressing application
for clinical use.
PMID- 29345903
TI - Light-Emitting Diodes Based on Colloidal Silicon Quantum Dots with Octyl and
Phenylpropyl Ligands.
AB - Colloidal silicon quantum dots (Si QDs) hold ever-growing promise for the
development of novel optoelectronic devices such as light-emitting diodes (LEDs).
Although it has been proposed that ligands at the surface of colloidal Si QDs may
significantly impact the performance of LEDs based on colloidal Si QDs, little
systematic work has been carried out to compare the performance of LEDs that are
fabricated using colloidal Si QDs with different ligands. Here, colloidal Si QDs
with rather short octyl ligands (Octyl-Si QDs) and phenylpropyl ligands (PhPr-Si
QDs) are employed for the fabrication of LEDs. It is found that the optical power
density of PhPr-Si QD LEDs is larger than that of Octyl-Si QD LEDs. This is due
to the fact that the surface of PhPr-Si QDs is more oxidized and less defective
than that of Octyl-Si QDs. Moreover, the benzene rings of phenylpropyl ligands
significantly enhance the electron transport of QD LEDs. It is interesting that
the external quantum efficiency (EQE) of PhPr-Si QD LEDs is lower than that of
Octyl-Si QD LEDs because the benzene rings of phenylpropyl ligands suppress the
hole transport of QD LEDs. The unbalance between the electron and hole injection
in PhPr-Si QD LEDs is more serious than that in Octyl-Si QD LEDs. The currently
obtained highest optical power density of ~0.64 mW/cm2 from PhPr-Si QD LEDs and
highest EQE of ~6.2% from Octyl-Si QD LEDs should encourage efforts to further
advance the development of high-performance optoelectronic devices based on
colloidal Si QDs.
PMID- 29345904
TI - Enzyme-Initiated Quinone-Chitosan Conjugation Chemistry: Toward A General in Situ
Strategy for High-Throughput Photoelectrochemical Enzymatic Bioanalysis.
AB - Herein we report a general and novel strategy for high-throughput
photoelectrochemical (PEC) enzymatic bioanalysis on the basis of enzyme-initiated
quinone-chitosan conjugation chemistry (QCCC). Specifically, the strategy was
illustrated by using a model quinones-generating oxidase of tyrosinase (Tyr) to
catalytically produce 1,2-bezoquinone or its derivative, which can easily and
selectively be conjugated onto the surface of the chitosan deposited PbS/NiO/FTO
photocathode via the QCCC. Upon illumination, the covalently attached quinones
could act as electron acceptors of PbS quantum dots (QDs), improving the
photocurrent generation and thus allowing the elegant probing of Tyr activity.
Enzyme cascades, such as alkaline phosphatase (ALP)/Tyr and beta-galactosidase
(Gal)/Tyr, were further introduced into the system for the successful probing of
the corresponding targets. This work features not only the first use of QCCC in
PEC bioanalysis but also the separation of enzymatic reaction from the
photoelectrode as well as the direct signal recording in a split-type protocol,
which enables quite convenient and high-throughput detection as compared to
previous formats. More importantly, by using numerous other oxidoreductases that
involve quinones as reactants/products, this protocol could serve as a common
basis for the development of a new class of QCCC-based PEC enzymatic bioanalysis
and further extended for general enzyme-labeled PEC bioanalysis of versatile
targets.
PMID- 29345905
TI - Chelate-Assisted Ring-Closing Metathesis: A Strategy for Accelerating
Macrocyclization at Ambient Temperatures.
AB - Ring-closing metathesis (RCM) offers versatile catalytic routes to macrocycles,
with applications ranging from perfumery to production of antiviral drugs.
Unwanted oligomerization, however, is a long-standing challenge. Oligomers can be
converted into the cyclic targets by catalysts that are sufficiently reactive to
promote backbiting (e.g., Ru complexes of N-heterocyclic carbenes; NHCs), but
catalyst decomposition limits yields and selectivity. Incorporation of a
hemilabile o-dianiline (ODA) chelate into new catalysts of the form
RuCl2(NHC)(ODA)(=CHPh) accelerates macrocyclization, particularly for dienes
bearing polar sites capable of H-bonding: it may also inhibit catalyst
decomposition during metathesis. Significant improvements relative to prior Ru
NHC catalysts result, with fast macrocyclization of conformationally flexible
dienes at room temperature.
PMID- 29345906
TI - Prediction of Hot Spots at Myeloid Cell Leukemia-1-Inhibitor Interface Using
Energy Estimation and Alanine Scanning Mutagenesis.
AB - Myeloid cell leukemia 1 (Mcl1) is an antiapoptotic protein that plays central
role in apoptosis regulation. Also, Mcl1 has the potency to resist apoptotic cues
resulting in up-regulation and cancer cell protection. A molecular probe that has
the potential to specifically target Mcl1 and thereby provoke its down-regulatory
activity is very essential. The aim of the current study is to probe the internal
conformational dynamics of protein motions and potential binding mechanism in
response to a series of picomolar range Mcl1 inhibitors using explicit-solvent
molecular dynamics (MD) simulations. Subsequently, domain cross-correlation and
principal component analysis was performed on the snapshots obtained from the MD
simulations. Our results showed significant differences in the internal
conformational dynamics of Mcl1 with respect to binding affinity values of
inhibitors. Further, the binding free energy estimation, using three different
samples, was performed on the MD simulations and revealed that the predicted
energies (DeltaGmmgbsa) were in good correlation with the experimental values
(DeltaGexpt). Also, the energies obtained using all sampling models were
efficiently ranked. Subsequently, the decomposition energy analysis highlighted
the major energy-contributing residues at the Mcl1 binding pocket. Computational
alanine scanning performed on high energy-contributing residues predicted the hot
spot residues. The dihedral angle analysis using MD snapshots on the predicted
hot spot residue exhibited consistency in side chain conformational motion that
ultimately led to strong binding affinity values. The findings from the present
study might provide valuable guidelines for the design of novel Mcl1 inhibitors
that might significantly improve the specificity for new-generation
chemotherapeutic agents.
PMID- 29345901
TI - Playing with the Molecules of Life.
AB - Our understanding of the complex molecular processes of living organisms at the
molecular level is growing exponentially. This knowledge, together with a
powerful arsenal of tools for manipulating the structures of macromolecules, is
allowing chemists to to harness and reprogram the cellular machinery in ways
previously unimaged. Here we review one example in which the genetic code itself
has been expanded with new building blocks that allow us to probe and manipulate
the structures and functions of proteins with unprecedented precision.
PMID- 29345907
TI - Effects of Plant Sterols or beta-Cryptoxanthin at Physiological Serum
Concentrations on Suicidal Erythrocyte Death.
AB - The eryptotic and hemolytic effects of a phytosterol (PS) mixture (beta
sitosterol, campesterol, stigmasterol) or beta-cryptoxanthin (beta-Cx) at
physiological serum concentration and their effect against oxidative stress
induced by tert-butylhydroperoxide (tBOOH) (75 and 300 MUM) were evaluated. beta
Cryptoxanthin produced an increase in eryptotic cells, cell volume, hemolysis,
and glutathione depletion (GSH) without ROS overproduction and intracellular Ca2+
influx. Co-incubation of both bioactive compounds protected against beta-Cx
induced eryptosis. Under tBOOH stress, PS prevented eryptosis, reducing Ca2+
influx, ROS overproduction and GSH depletion at 75 MUM, and hemolysis at both
tBOOH concentrations. beta-Cryptoxanthin showed no cytoprotective effect. Co
incubation with both bioactive compounds completely prevented hemolysis and
partially prevented eryptosis as well as GSH depletion induced by beta-Cx plus
tBOOH. Phytosterols at physiological serum concentrations help to prevent pro
eryptotic and hemolytic effects and are promising candidate compounds for
ameliorating eryptosis-associated diseases.
PMID- 29345908
TI - A Small-Molecule Inhibitor of Human DNA Polymerase eta Potentiates the Effects of
Cisplatin in Tumor Cells.
AB - Translesion DNA synthesis (TLS) performed by human DNA polymerase eta (hpol eta)
allows tolerance of damage from cis-diamminedichloroplatinum(II) (CDDP or
cisplatin). We have developed hpol eta inhibitors derived from N-aryl-substituted
indole barbituric acid (IBA), indole thiobarbituric acid (ITBA), and indole
quinuclidine scaffolds and identified 5-((5-chloro-1-(naphthalen-2-ylmethyl)-1H
indol-3-yl)methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (PNR-7-02), an
ITBA derivative that inhibited hpol eta activity with an IC50 value of 8 MUM and
exhibited 5-10-fold specificity for hpol eta over replicative pols. We conclude
from kinetic analyses, chemical footprinting assays, and molecular docking that
PNR-7-02 binds to a site on the little finger domain and interferes with the
proper orientation of template DNA to inhibit hpol eta. A synergistic increase in
CDDP toxicity was observed in hpol eta-proficient cells co-treated with PNR-7-02
(combination index values = 0.4-0.6). Increased gammaH2AX formation accompanied
treatment of hpol eta-proficient cells with CDDP and PNR-7-02. Importantly, PNR-7
02 did not impact the effect of CDDP on cell viability or gammaH2AX in hpol eta
deficient cells. In summary, we observed hpol eta-dependent effects on DNA
damage/replication stress and sensitivity to CDDP in cells treated with PNR-7-02.
The ability to employ a small-molecule inhibitor of hpol eta to improve the
cytotoxic effect of CDDP may aid in the development of more effective
chemotherapeutic strategies.
PMID- 29345909
TI - Metabolomics Study Reveals Enhanced Inhibition and Metabolic Dysregulation in
Escherichia coli Induced by Lactobacillus acidophilus-Fermented Black Tea
Extract.
AB - This study examined the ability of Lactobacillus acidophilus (LA) to ferment
black tea extract (BTE) and the enhancement of Escherichia coli cellular uptake
of phenolic compounds when these bacteria were incubated with fermented BTE. The
inhibitory effects of BTE to E. coli bacteria with and without fermentation were
compared. Several intracellular phenolic compounds as well as metabolic profiles
of E. coli with and without treatments were also determined using a high
performance liquid chromatography-tandem mass spectrometry-based approach. Our
results showed that of three concentrations from the non-fermented BTE treatment,
only the extract from the 25 mg/mL tea leaves solution could inhibit E. coli
survival, while LA-fermented BTE extract from 5, 10, and 25 mg/mL tea leaves
solutions all inhibited E. coli growth significantly. Intracellular
concentrations of (+)-catechin-3-gallate/(-)-epicatechin-3-gallate and (+)
catechin/(-)-epicatechin were significantly higher when E. coli was treated with
fermented BTE in comparison to non-fermented BTE. Scanning electron microscopy
images indicated that the intracellular phenolic compounds inhibited E. coli
growth by increasing endogenous oxidative stress. Metabolic profiles of E. coli
were also investigated to understand their metabolic response when treated with
BTE, and significant metabolic changes of E. coli were observed. Metabolic
profile data were further analyzed using partial least squares discriminant
analysis to distinguish the fermented BTE treatment group from the control group
and the non-fermented BTE treatment group. The results indicated a large-scale E.
coli metabolic dysregulation induced by the fermented BTE. Our findings showed
that LA fermentation can be an efficient approach to enhance phenolic inhibition
of bacterial cells through increased endogenous oxidative stress and dysregulated
metabolic activities.
PMID- 29345910
TI - Qualitative and Quantitative Analysis of Ethanolic Extract and Phenolic Fraction
of Jatropha aethiopica (Euphorbiaceae) Leaves and Their Hypoglycemic Potential.
AB - Although Jatropha aethiopica, popularly known in Cuba as "mata diabetes", is used
in salads and as a dietary supplement, its chemical composition and antidiabetic
properties yet remains unclear. In this work, we evaluate the qualitative and
quantitative composition of ethanolic extract (EE) and phenolic fraction (PF) of
Jatropha aethiopica leaves and their hypoglycemic and hypolipidemic activity.
Chemical fractionation of the ethanolic extract yielded nine compounds, which
included protocatechuic acid (1), chlorogenic acid (2), caffeic acid (3),
quercetin 3-O-alpha-l-rhamnopyranosyl-(1 -> 2)-[alpha-l-rhamnopyranolsyl-(1 ->
6)]-beta-d-galactopyranoside (4), a new kaempferol 3-O-alpha-l-rhamnopyranosyl-(1
-> 4)-[alpha-l-rhamnopyranolsyl-(1 -> 6)]-beta-d-galactopyranoside (5),
kaempferol 3-O-alpha-l-rhamnopyranosyl-(1 -> 2)-[alpha-l-rhamnopyranolsyl-(1 ->
6)]-beta-d-glucopyranoside (6), rutin (7), kaempferol 3-O-alpha-l-rhamnopyranosyl
(1 -> 6)-beta-d-glucopyranoside (8), and quercetin (9). The compounds (1, 4-7)
were quantified by high-performance liquid chromatography photodiode array
detection (HPLC-PDA) in both the ethanolic extract (62.65 +/- 0.15 mg/g) and
phenolic fraction (61.72 +/- 0.23 mg/g). The results obtained show that both
ethanolic extract and phenolic fraction contributed toward the improvement of
glucose tolerance, which in turn led to a decline in the glucose levels.
Remarkably, the ethanolic extract presented a relatively higher promising effect
compared to metformin.
PMID- 29345911
TI - Role of Glycanation and Convertase Maturation of Soluble Glypican-3 in Inhibiting
Proliferation of Hepatocellular Carcinoma Cells.
AB - Glypican 3 (GPC3) is a complex heparan sulfate proteoglycan associated with the
outer surface of the plasma membrane by a glycosylphosphatidylinositol (GPI)
anchor. It is also N-glycosylated and processed by a furin-like convertase. GPC3
has numerous biological functions. Although GPC3 is undetectable in normal liver
tissue, it is abnormally and highly overexpressed in hepatocellular carcinoma
(HCC). Interestingly, proliferation of HCC cells such as HepG2 and HuH7 is
inhibited when they express a soluble form of GPC3 after lentiviral transduction.
To obtain more insight into the role of some of its post-translational
modifications, we designed a mutant GPC3, sGPC3m, without its GPI anchor,
convertase cleavage site, and glycosaminoglycan chains. The highly pure sGPC3m
protein strongly inhibited HuH7 and HepG2 cell proliferation in vitro and induced
a significant increase in their cell doubling time. It changed the morphology of
HuH7 cells but not that of HepG2. It induced the enlargement of HuH7 cell nuclear
area and the restructuration of adherent cell junctions. Unexpectedly, for both
cell types, the levels of apoptosis, cell division, and beta-catenin were not
altered by sGPC3m, although growth inhibition was very efficient. Overall, our
data show that glycanation and convertase maturation are not required for sGPC3m
to inhibit HCC cell proliferation.
PMID- 29345912
TI - A (Re)Discovery of the Fom3 Substrate.
PMID- 29345913
TI - Non-Centrosymmetric RbNaMgP2O7 with Unprecedented Thermo-Induced Enhancement of
Second Harmonic Generation.
AB - It is of great difficulty to obtain deep-UV transparent materials with enhanced
second harmonic generation (SHG), mainly limited by the theoretically poor
transparency of these materials in the deep-UV spectral region. Here we report a
new noncentrosymmetric, deep-UV transparent phosphate RbNaMgP2O7, which undergoes
a thermo-induced reversible phase transition (at a high temperature of 723 K) and
correspondingly an evident SHG enhancement up to ~1.5 times. The phase transition
is aroused by the twist of [P2O7]4- dimers with deviation from the P-O-P
equilibrium positions. Theoretical analyses reveal that the enhanced SHG can be
ascribed to the thermo-induced collective alignment of SHG-active [P2O7]4- dimers
along the polar axis of high-temperature phase. This work provides an
unprecedented physical routine (to SHG-enhanced materials) that is distinguished
from the traditional one by chemical design and synthesis.
PMID- 29345914
TI - Comparative Analysis of EPA/DHA-PL Forage and Liposomes in Orotic Acid-Induced
Nonalcoholic Fatty Liver Rats and Their Related Mechanisms.
AB - Nonalcoholic fatty liver disease (NAFLD) has become one predictive factor of
death from various illnesses. The present study was to comparatively investigate
the effects of eicosapentaenoic acid-enriched and docosahexaenoic acid-enriched
phospholipids forage (EPA-PL and DHA-PL) and liposomes (lipo-EPA and lipo-DHA) on
NAFLD and demonstrate the possible protective mechanisms involved. The additive
doses of EPA-PL and DHA-PL in all treatment groups were 1% of total diets,
respectively. The results showed that Lipo-EPA could significantly improve
hepatic function by down-regulating orotic acid-induced serum aspartate
aminotransferase (AST) and alanine aminotransferase (ALT) levels by 55.6% and
34.2%, respectively (p < 0.01). Moreover, lipo-EPA exhibited excellent inhibition
on the mRNA expression of SREBP-1c and FAS at the values of 0.454 +/- 0.09 (p <
0.01) and 0.523 +/- 0.08 (p < 0.01), respectively, thus ameliorating OA-induced
NAFLD. Meanwhile, lipo-EPA could significantly suppress the SREBP-2 and HMGR
levels (31.4% and 66.7%, p < 0.05, respectively). In addition, EPA-PL and lipo
DHA could also significantly suppress hepatic lipid accumulation mainly by
enhancement of hepatic lipolysis and cholesterol efflux. Furthermore, DHA-PL
played a certain role in inhibiting hepatic lipogenesis and accelerating
cholesterol efflux. The results obtained in this work might contribute to the
understanding of the biological activities of EPA/DHA-PL and liposomes and
further investigation on its potential application values for food supplements.
PMID- 29345915
TI - The Effect of Water on Quinone Redox Mediators in Nonaqueous Li-O2 Batteries.
AB - The parasitic reactions associated with reduced oxygen species and the difficulty
in achieving the high theoretical capacity have been major issues plaguing
development of practical nonaqueous Li-O2 batteries. We hereby address the above
issues by exploring the synergistic effect of 2,5-di-tert-butyl-1,4-benzoquinone
and H2O on the oxygen chemistry in a nonaqueous Li-O2 battery. Water stabilizes
the quinone monoanion and dianion, shifting the reduction potentials of the
quinone and monoanion to more positive values (vs Li/Li+). When water and the
quinone are used together in a (largely) nonaqueous Li-O2 battery, the cell
discharge operates via a two-electron oxygen reduction reaction to form Li2O2,
with the battery discharge voltage, rate, and capacity all being considerably
increased and fewer side reactions being detected. Li2O2 crystals can grow up to
30 MUm, more than an order of magnitude larger than cases with the quinone alone
or without any additives, suggesting that water is essential to promoting a
solution dominated process with the quinone on discharging. The catalytic
reduction of O2 by the quinone monoanion is predominantly responsible for the
attractive features mentioned above. Water stabilizes the quinone monoanion via
hydrogen-bond formation and by coordination of the Li+ ions, and it also helps
increase the solvation, concentration, lifetime, and diffusion length of reduced
oxygen species that dictate the discharge voltage, rate, and capacity of the
battery. When a redox mediator is also used to aid the charging process, a high
power, high energy density, rechargeable Li-O2 battery is obtained.
PMID- 29345916
TI - Monitoring H2O2 inside Aspergillus fumigatus with an Integrated Microelectrode:
The Role of Peroxiredoxin Protein Prx1.
AB - Peroxiredoxins (Prx) are important proteins involved in hydroperoxide degradation
and are related to virulence in several pathogens, including Aspergillus
fumigatus. In this work, in vivo studies on the degradation of hydrogen peroxide
(H2O2) in the microenvironment of A. fumigatus fungus were performed by using an
integrated Pt microelectrode. Three A. fumigatus strains were used to confirm the
role of the cytosolic protein Prx1 in the defense mechanism of this
microorganism: a wild-type strain, capable to expressing the protein Prx1; a
Deltaprx strain, whose gene prx1 was removed; and a genetically complemented
Deltaprx1::prx1+ strain generated from the Deltaprx1 and in which the gene prx1
was reintroduced. The fabricated microelectrode was shown to be a reliable inert
probe tip for in situ and real-time measurements of H2O2 in such
microenvironments, with potential applications in investigations involving the
mechanism of oxidative stress.
PMID- 29345917
TI - Anisotropic Assembly of Ag52 and Ag76 Nanoclusters.
AB - Although there has been an upsurge of interest in anisotropic assembly of
inorganic nanoparticles, atomically precise self-assembly of anisotropic metal
clusters is extremely rare. Herein, we presented two novel silver nanoclusters,
Ag52 (SD/Ag23) and Ag76 (SD/Ag24), which are interiorly templated by five MoO42-
and a pair of Mo6O228- anions, respectively, and coprotected by bridging RSH and
terminal diphosphine ligands exteriorly. Regiospecific distribution diphosphine
ligands on the surface and the arrangement of multiple molybdate templates within
the nanoclusters synergetically tailor their shapes to anisotropic oblate
spheroid and elongated rod, respectively. This work not only open up new avenues
for the synthesis of silver nanoclusters with novel metal skeleton shapes and
anisotropic surface structures but also give important insights for the
anisotropic growth of silver nanoclusters through surface modifications or/and
template organizations.
PMID- 29345918
TI - Anti-Inflammatory and Antioxidant Activities from the Basolateral Fraction of
Caco-2 Cells Exposed to a Rosmarinic Acid Enriched Extract.
AB - The potential use of Origanum majorana L. as a source of bioavailable phenolic
compounds, specifically rosmarinic acid (RA), has been evaluated. Phenolic
bioavailability was tested using an in vitro digestion process followed by a Caco
2 cellular model of intestinal absorption. The high-performance liquid
chromatography-photodiode array detector-tandem mass spectrometry (HPLC-PAD
MS/MS) analysis showed the main components in the extract were 6-hydroxyluteolin
7-O-glucoside and rosmarinic acid, followed by luteolin-O-glucoside. After
digestion process, the amount of total phenolic compounds (TPC) only decreased
slightly, although a remarkable reduction in RA (near 50%) was detected.
Bioavailable fraction contained 7.37 +/- 1.39 mg/L digested extract of RA with
small quantities of lithospermic acid and diosmin and presented an important
antioxidant activity (0.89 +/- 0.09 mmol Trolox/L digested extract). Besides,
this bioavailable fraction produced a significant inhibition in TNF-alpha, IL
1beta, and IL-6 secretion, using a human THP-1 macrophages model. Therefore, RA
content in the basolateral compartment could play an important role in the
antioxidant and anti-inflammatory activities found.
PMID- 29345919
TI - Using Isomeric and Metabolic Ratios of DDT To Identify the Sources and Fate of
DDT in Chinese Agricultural Topsoil.
AB - The metabolic ratio of (p,p'-DDE + p,p'-DDD)/p,p'-DDT or p,p'-DDE/p,p'-DDT has
been used previously to estimate the approximate half-life of p,p'-DDT, with a
relatively unclear concept of "old" and "new" sources of p,p'-DDT and without
paying attention to the influence by dicofol-type DDT contributed from the more
recent usage of dicofol. Based on the isomeric ratio of o,p'-DDT/p,p'-DDT to
distinguish the sources of DDT, this study used the corrected metabolic ratio of
(p,p'-DDE + p,p'-DDD)/p,p'-DDT to estimate a more accurate half-life of p,p'-DDT
using a model-based approach. This indicates the average half-life of p,p'-DDT in
Chinese topsoils was 14.2 +/- 0.9 years with dicofol-type DDT input considered.
In deeper soil, the half-life was >30 years and the metabolic pathway of p,p'-DDT
was significantly different with topsoil's. Further analysis on the fraction of
DDT from technical DDT suggested that a region that had been sprayed with
technical DDT was likely to have been sprayed with dicofol as well, but the
monitoring residues of DDT in topsoil mainly derive from historical use of
technical DDT.
PMID- 29345921
TI - Molecular Mechanisms in the Selectivity of Nonsteroidal Anti-Inflammatory Drugs.
AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) 1 and
2 with varying degrees of selectivity. A group of COX-2 selective inhibitors
coxibs-binds in a time-dependent manner through a three-step mechanism, utilizing
a side pocket in the binding site. Coxibs have been extensively probed to
identify the structural features regulating the slow tight-binding mechanism
responsible for COX-2 selectivity. In this study, we further probe a structurally
and kinetically diverse data set of COX inhibitors in COX-2 by molecular dynamics
and free energy simulations. We find that the features regulating the high
affinities associated with time-dependency in COX depend on the inhibitor
kinetics. In particular, most time-dependent inhibitors share a common structural
binding mechanism, involving an induced-fit rotation of the side-chain of Leu531
in the main binding pocket. The high affinities of two-step slow tight-binding
inhibitors and some slow reversible inhibitors can thus be explained by the
increased space in the main binding pocket after this rotation. Coxibs that
belong to a separate class of slow tight-binding inhibitors benefit more from the
displacement of the neighboring side-chain of Arg513, exclusive to the COX-2 side
pocket. This displacement further stabilizes the aforementioned rotation of
Leu531 and can explain the selectivity of coxibs for COX-2.
PMID- 29345920
TI - Acetylation by Eis and Deacetylation by Rv1151c of Mycobacterium tuberculosis
HupB: Biochemical and Structural Insight.
AB - Bacterial nucleoid-associated proteins (NAPs) are critical to genome integrity
and chromosome maintenance. Post-translational modifications of bacterial NAPs
appear to function similarly to their better studied mammalian counterparts. The
histone-like NAP HupB from Mycobacterium tuberculosis (Mtb) was previously
observed to be acetylated by the acetyltransferase Eis, leading to genome
reorganization. We report biochemical and structural aspects of acetylation of
HupB by Eis. We also found that the SirT-family NAD+-dependent deacetylase
Rv1151c from Mtb deacetylated HupB in vitro and characterized the deacetylation
kinetics. We propose that activities of Eis and Rv1151c could regulate the
acetylation status of HupB to remodel the mycobacterial chromosome in response to
environmental changes.
PMID- 29345923
TI - Capped Polyoxometalate Pillars between Metal-Organic Layers for Transferring a
Supramolecular Structure into a Covalent 3D Framework.
AB - Two robust metal-organic frameworks (MOFs), {H4[Ni(pi-H2O)2]2[Ni(rt
H2O)2]8Ni4(Tri)24}[VIVW12O40]2.24H2O (1) and {H[Ni(pi-O)2]2[Ni(rt
H2O)2]8Ni4(Tri)24}[VIVW10VV2O40V2][VIVW9VV3O40VIV2].24H2O (2) (Tri = 1,2,4
triazole), composed of polyoxometalates (POMs) and metal-organic units, were
designed and synthesized by a hydrothermal method. Structure analysis indicates
that there is a metal-organic crown [{Ni3(Tri)6(H2O)4}4] ({Ni12}) in these two
compounds. In 1, the {Ni12} crown embraces four pendant Tri ligands that could
capture a cationic [Ni(H2O)2]2+ group, resulting in the Ni13-Tri building unit
[Ni(H2O)2{Ni3(Tri)6(H2O)4}4] ({Ni13}). The {Ni13} building unit was fused
together by Tri bridges into the 2D metal-organic layers, which are pillared by a
typical Keggin-type POM [VW12O40]4- to construct a 3D supramolecular framework
via the hydrogen bonds. Interestingly, the 2D metal-organic layer in 1 was
successfully transferred into a 3D covalent MOF via extension of the length of
the pillars by capping a Keggin-type POM with V-O units. Moreover,
electrochemical behaviors and electrocatalytic properties of these two compounds
were both studied, which can act as bifunctional electrocatalysts toward the
reduction of H2O2 and oxidation of nitrite in neutral aqueous solution.
PMID- 29345924
TI - Domain-Based Local Pair Natural Orbital Version of Mukherjee's State-Specific
Coupled Cluster Method.
AB - This article reports development of a local variant of Mukherjee's state-specific
multireference coupled cluster method based on the domain-based pair natural
orbital approach (DLPNO-MkCC). The current implementation is restricted to
connected single and double excitations and model space with up to biexcited
references. The performance of the DLPNO-MkCCSD was tested on calculations of
tetramethyleneethane. The results show that above 99.9% of the correlation energy
was recovered, with respect to the conventional MkCC method. To demonstrate the
applicability of the method to large systems, singlet-triplet gaps of triangulene
and bis(1-(2,6-diisopropylphenyl)-3,3,5,5-tetramethylpyrrolidine-2
ylidene)beryllium complex were studied. For the last system (105 atoms), we were
able to perform a calculation in cc-pVTZ with 2158 basis functions on a single
CPU in less than 9 days.
PMID- 29345922
TI - Efficient Fusion at Neutral pH by Human Immunodeficiency Virus gp41 Trimers
Containing the Fusion Peptide and Transmembrane Domains.
AB - Human immunodeficiency virus (HIV) is membrane-enveloped, and an initial
infection step is joining/fusion of viral and cell membranes. This step is
catalyzed by gp41, which is a single-pass integral viral membrane protein. The
protein contains an ~170-residue ectodomain located outside the virus that is
important for fusion and includes the fusion peptide (FP), N-helix, loop, C
helix, and viral membrane-proximal external region (MPER). The virion initially
has noncovalent complexes between three gp41 ectodomains and three gp120
proteins. A gp120 contains ~500 residues and functions to identify target T-cells
and macrophages via binding to specific protein receptors of the target cell
membrane. gp120 moves away from the gp41 ectodomain, and the ectodomain is
thought to bind to the target cell membrane and mediate membrane fusion. The
secondary and tertiary structures of the ectodomain are different in the initial
complex with gp120 and the final state without gp120. There is not yet imaging of
gp41 during fusion, so the temporal relationship between the gp41 and membrane
structures is not known. This study describes biophysical and functional
characterization of large gp41 constructs that include the ectodomain and
transmembrane domain (TM). Significant fusion is observed of both neutral and
anionic vesicles at neutral pH, which reflects the expected conditions of
HIV/cell fusion. Fusion is enhanced by the FP, which in HIV/cell fusion likely
contacts the host membrane, and the MPER and TM, which respectively interfacially
contact and traverse the HIV membrane. Initial contact with vesicles is made by
protein trimers that are in a native oligomeric state that reflects the initial
complex with gp120 and also is commonly observed for the ectodomain without
gp120. Circular dichroism data support helical structure for the N-helix, C
helix, and MPER and nonhelical structure for the FP and loop. Distributions of
monomer, trimer, and hexamer states are observed by size-exclusion chromatography
(SEC), with dependences on solubilizing detergent and construct. These SEC and
other data are integrated into a refined working model of HIV/cell fusion that
includes dissociation of the ectodomain into gp41 monomers followed by folding
into hairpins that appose the two membranes, and subsequent fusion catalysis by
trimers and hexamers of hairpins. The monomer and oligomer gp41 states may
therefore satisfy dual requirements for HIV entry of membrane apposition and
fusion.
PMID- 29345925
TI - Catalytic Mechanism of the Ubiquitin-Like NEDD8 Transfer in RING E3-E2~NEDD8
Target Complex from QM/MM Free Energy Simulations.
AB - Ubiquitin-like (UBL) protein modifications play a key role in regulating protein
function. In contrast to the ubiquitin (UB) and small ubiquitin-like modifier
(SUMO) which are ligated to a massive segment of proteome, the UBL NEDD8 is
highly selective for modifying a lysine residue on closely related cullin
proteins (CULs). In this study, the X-ray structure of a trapped E3-E2~NEDD8
target intermediate (RBX1-UBC1~NEDD8-CUL1-DCN1) is used to build computer models,
and combined quantum mechanics/molecular mechanics (QM/MM) molecular dynamics
(MD) and free energy (potential of mean force) simulations are performed to
investigate the catalytic mechanism of the NEDD8 transfer from E2 to the lysine
residue (K720) on the substrate in the complex. The role of the active site
residues is examined. The simulation results show that either E117 or D143 from
E2 may be able to work as a general base catalyst to deprotonate K720 on the
substrate, and K720 can then perform the nucleophilic attack on the thioester
bond linking E2 and NEDD8. It is also shown that the formation of a new
isopeptide bond between K720 and NEDD8 and the breaking of the thioester bond are
concerted based on the computer simulations. Furthermore, the results suggest
that K720 may act as a general acid catalyst to protonate the leaving group of
C111 from E2. The free energy barrier for nucleophilic attack is estimated to be
14-15 kcal/mol based on the free energy simulations.
PMID- 29345926
TI - Investigation on the Thermodynamic Dissociation Kinetics of Photosystem II
Supercomplexes To Determine the Binding Strengths of Light-Harvesting Complexes.
AB - The photosystem II (PSII) supercomplex splits water utilizing light energy and is
composed of a core dimer complex surrounded by light-harvesting complexes (LHCs).
In green algae, the major LHCs which are LHCII trimers have thus far been
categorized into strongly, moderately, or loosely binding LHCII trimers based on
their predicted binding to core complexes. However, the binding energies have
been indirectly predicted based on the presence or absence of LHCII trimers in
the PSII supercomplex under electron microscopy and have not been determined
experimentally. In this study, we investigated the binding of LHCII trimers by
analyzing thermodynamic dissociation kinetics using isolated PSII supercomplexes.
We identified two activation energies for dissociation of LHCII trimers: 54 +/-
19 and 134 +/- 8 kJ/mol. This result indicated the types of intermolecular
interactions between LHCII trimers and core complexes.
PMID- 29345927
TI - Embedded Multireference Coupled Cluster Theory.
AB - Internally contracted multireference coupled cluster (icMRCC) theory is embedded
within multireference perturbation theory (MRPT) to calculate energy differences
in large strongly correlated systems. The embedding scheme is based on
partitioning the orbital spaces of a complete active space self-consistent field
(CASSCF) wave function, with a truncated virtual space constructed by
transforming selected projected atomic orbitals (PAOs). MRPT is applied to the
environment using a subtractive embedding approach that also allows for
multilayer embedding. Benchmark calculations are presented for biradical bond
dissociation, spin splitting in a heterocyclic carbene and hydrated Fe(II), and
for the super-exchange coupling constant in solid nickel oxide. The method is
further applied to two large transition metal complexes with a triple-zeta basis
set: an iron complex with 175 atoms and 2939 basis functions, and a nickel
complex with 231 atoms, and 4175 basis functions.
PMID- 29345928
TI - Physicochemical Properties of Whey-Protein-Stabilized Astaxanthin Nanodispersion
and Its Transport via a Caco-2 Monolayer.
AB - Astaxanthin nanodispersion was prepared using whey protein isolate (WPI) and
polymerized whey protein (PWP) through an emulsification-evaporation technique.
The physicochemical properties of the astaxanthin nanodispersion were evaluated,
and the transport of astaxanthin was assessed using a Caco-2 cell monolayer
model. The astaxanthin nanodispersions stabilized by WPI and PWP (2.5%, w/w) had
a small particle size (121 +/- 4.9 and 80.4 +/- 5.9 nm, respectively), negative
zeta potential (-19.3 +/- 1.5 and -35.0 +/- 2.2 mV, respectively), and high
encapsulation efficiency (92.1 +/- 2.9 and 93.5 +/- 2.4%, respectively).
Differential scanning calorimetry curves indicated that amorphous astaxanthin
existed in both astaxanthin nanodispersions. Whey-protein-stabilized astaxanthin
nanodispersion showed resistance to pepsin digestion but readily released
astaxanthin after trypsin digestion. The nanodispersions showed no cytotoxicity
to Caco-2 cells at a protein concentration below 10 mg/mL. WPI- and PWP
stabilized nanodispersions improved the apparent permeability coefficient (Papp)
of Caco-2 cells to astaxanthin by 10.3- and 16.1-fold, respectively. The results
indicated that whey-protein-stabilized nanodispersion is a good vehicle to
deliver lipophilic bioactive compounds, such as astaxanthin, and to improve their
bioavailability.
PMID- 29345929
TI - Antihypertensive Effects, Molecular Docking Study, and Isothermal Titration
Calorimetry Assay of Angiotensin I-Converting Enzyme Inhibitory Peptides from
Chlorella vulgaris.
AB - The aim of this work is to explore angiotensin I-converting enzyme (ACE)
inhibitory peptides from Chlorella vulgaris (C. vulgaris) and discover the
inhibitory mechanism of the peptides. After C. vulgaris proteins were
gastrointestinal digested in silico, several ACE inhibitory peptides with C
terminal tryptophan were screened. Among them, two novel noncompetitive ACE
inhibitors, Thr-Thr-Trp (TTW) and Val-His-Trp (VHW), exhibited the highest
inhibitory activity indicated by IC50 values 0.61 +/- 0.12 and 0.91 +/- 0.31 MUM,
respectively. Both the peptides were demonstrated stable against gastrointestinal
digestion and ACE hydrolysis. The peptides were administrated to spontaneously
hypertensive rats (SHRs) in the dose 5 mg/kg body weight, and VHW could decrease
50 mmHg systolic blood pressure of SHRs (p < 0.05). Molecular docking displayed
that both TTW and VHW formed six hydrogen bonds with active site pockets of ACE.
Besides, isothermal titration calorimetry assay discovered that VHW could form
more stable complex with ACE than TTW. Therefore, VHW was an excellent ACE
inhibitor.
PMID- 29345930
TI - alpha-Amino-beta-carboxymuconate-epsilon-semialdehyde Decarboxylase (ACMSD)
Inhibitors as Novel Modulators of De Novo Nicotinamide Adenine Dinucleotide
(NAD+) Biosynthesis.
AB - NAD+ has a central function in linking cellular metabolism to major cell
signaling and gene-regulation pathways. Defects in NAD+ homeostasis underpin a
wide range of diseases, including cancer, metabolic disorders, and aging.
Although the beneficial effects of boosting NAD+ on mitochondrial fitness,
metabolism, and lifespan are well established, to date, no therapeutic enhancers
of de novo NAD+ biosynthesis have been reported. Herein we report the discovery
of 3-[[[5-cyano-1,6-dihydro-6-oxo-4-(2-thienyl)-2
pyrimidinyl]thio]methyl]phenylacetic acid (TES-1025, 22), the first potent and
selective inhibitor of human ACMSD (IC50 = 0.013 MUM) that increases NAD+ levels
in cellular systems. The results of physicochemical-property, ADME, and safety
profiling, coupled with in vivo target-engagement studies, support the hypothesis
that ACMSD inhibition increases de novo NAD+ biosynthesis and position 22 as a
first-class molecule for the evaluation of the therapeutic potential of ACMSD
inhibition in treating disorders with perturbed NAD+ supply or homeostasis.
PMID- 29345931
TI - Umbrella Sampling and X-ray Crystallographic Analysis Unveil an Arg-Asp Gate
Facilitating Inhibitor Binding Inside Phosphopantetheine Adenylyltransferase
Allosteric Cleft.
AB - Phosphopantetheine adenylyltransferase (PPAT) is a rate-limiting enzyme essential
for biosynthesis of coenzyme A (CoA), which in turn is responsible to regulate
the secretion of exotoxins via type III secretion system in Pseudomonas
aeruginosa, causing severe health concerns ranging from nosocomial infections to
respiratory failure. Acetyl coenzyme A (AcCoA) is a newly reported inhibitor of
PPAT, believed to regulate the cellular levels of CoA and thereby the
pathogenesis. Very little is known so far regarding the mechanistic details of
AcCoA binding inside PPAT-binding cleft. Herein, we have used extensive umbrella
sampling simulations to decipher mechanistic insight into the inhibitor
accommodation inside the binding cavity. We found that R90 and D94 residues act
like a gate near the binding cavity to accommodate and stabilize the incoming
ligand. Mutational models concerning these residues also show considerable
difference in AcCoA-binding thermodynamics. To substantiate our findings, we have
solved the first crystal structure of apo-PPAT from P. aeruginosa, which also
found to agree with the simulation results. Collectively, these results describe
the mechanistic details of accommodation of inhibitor molecule inside PPAT
binding cavity and also offer valuable insight into regulating cellular levels of
CoA/AcCoA and thus controlling the pathogenicity.
PMID- 29345932
TI - Synthesis of Polysubstituted Quinolines from alpha-2-Aminoaryl Alcohols Via
Nickel-Catalyzed Dehydrogenative Coupling.
AB - This study reports a nickel-catalyzed sustainable synthesis of polysubstituted
quinolines from alpha-2-aminoaryl alcohols by a sequential dehydrogenation and
condensation process that offers the advantages of a low catalyst loading and
wide substrate scope. In contrast to earlier reported methods, this strategy
allows the use of both primary as well as secondary alpha-2-aminoaryl alcohols in
combination with either ketones or secondary alcohols for desired product
formation. Using this methodology, 30 substituted quinoline derivatives were
synthesized with up to 93% isolated yields.
PMID- 29345933
TI - Large-Scale Functional Group Symmetry-Adapted Perturbation Theory on Graphical
Processing Units.
AB - Symmetry-adapted perturbation theory (SAPT) is a valuable method for analyzing
intermolecular interactions. The functional group SAPT partition (F-SAPT) has
been introduced to provide additional insight into the origins of noncovalent
interactions. Until now, SAPT analysis has been too costly for large ligand
protein complexes where it could provide key insights for chemical modifications
that might improve ligand binding. In this paper, we present a large-scale
implementation of a variant of F-SAPT. Two pragmatic choices are made from the
outset to render the problem tractable: (1) Ab initio computation of dispersion
and exchange-dispersion is replaced with Grimme's empirical dispersion
correction. (2) Basis sets with augmented functions are avoided to allow for
efficient integral screening. These choices allow the F-SAPT analysis to be
written largely in terms of Coulomb and exchange matrix builds which have been
implemented efficiently on graphical processing units (GPUs). Our formulation of
F-SAPT is routinely applicable to molecules with well over 3000 atoms and 25,000
basis functions and is particularly optimized for the case where one monomer is
significantly larger than the other. This is demonstrated explicitly with results
from F-SAPT analysis of the full indinavir @ HIV-II protease complex (PDB ID 1HSG
) in a polarized double-zeta basis.
PMID- 29345934
TI - Zein Nanoparticles as Eco-Friendly Carrier Systems for Botanical Repellents
Aiming Sustainable Agriculture.
AB - Botanical repellents represent one of the main ways of reducing the use of
synthetic pesticides and the contamination of soil and hydric resources. However,
the poor stability and rapid degradation of these compounds in the environment
hinder their effective application in the field. Zein nanoparticles can be used
as eco-friendly carrier systems to protect these substances against premature
degradation, provide desirable release characteristics, and reduce toxicity in
the environment and to humans. In this study, we describe the preparation and
characterization of zein nanoparticles loaded with the main constituents of the
essential oil of citronella (geraniol and R-citronellal). The phytotoxicity,
cytotoxicity, and insect activity of the nanoparticles toward target and
nontarget organisms were also evaluated. The botanical formulations showed high
encapsulation efficiency (>90%) in the nanoparticles, good physicochemical
stability, and effective protection of the repellents against UV degradation.
Cytotoxicity and phytotoxicity assays showed that encapsulation of the botanical
repellents decreased their toxicity. Repellent activity tests showed that
nanoparticles containing the botanical repellents were highly repellent against
the Tetranychus urticae Koch mite. This nanotechnological formulation offers a
new option for the effective use of botanical repellents in agriculture, reducing
toxicity, protecting against premature degradation, and providing effective pest
control.
PMID- 29345935
TI - Rhodium-Catalyzed Asymmetric [2 + 2 + 2] Cycloaddition of Unsymmetrical
alpha,omega-Diynes with Acenaphthylene.
AB - It has been established that a cationic rhodium(I)/(R)-BINAP complex catalyzes
the asymmetric [2 + 2 + 2] cycloaddition of unsymmetrical alpha,omega-diynes with
acenaphthylene at room temperature to give the corresponding chiral multicyclic
compounds with high yields and ee values. Interestingly, enantioselectivity
highly depended on the structures of alpha,omega-diynes used. The structural
requirements of alpha,omega-diynes for high enantioselectivity were opposite to
those in our previously reported cationic rhodium(I)/(R)-Difluorphos complex
catalyzed asymmetric [2 + 2 + 2] cycloaddition of alpha,omega-diynes with indene.
PMID- 29345936
TI - Copper-Catalyzed One-Pot Cross-Dehydrogenative Thienannulation: Chemoselective
Access to Naphtho[2,1-b]thiophene-4,5-diones and Subsequent Transformation to
Benzo[a]thieno[3,2-c]phenazines.
AB - A facile, cost-effective, and highly efficient copper-catalyzed, TEMPO-mediated
straightforward synthesis of 2,3-disubstituted naphtho[2,1-b]thiophene-4,5-diones
has been achieved via cross-dehydrogenative thienannulation. The reaction
proceeded via in situ generated naphthalene-1,2-diones by dearomatization of beta
naphthols, followed by oxidative heteroannulation with alpha-enolic dithioesters
chemoselectively in an open flask. Further, the naphtho[2,1-b]thiophene-4,5
diones undergo l-proline-catalyzed cross-dehydrative coupling with ortho
phenylenediamine enabling pentacyclic benzo[a]thieno[3,2-c]phenazines in good
yields under solvent-free conditions. A mechanistic rationale for this cascade
reaction sequence is well supported by the control experiments.
PMID- 29345937
TI - Hole Hopping Rates in Organic Semiconductors: A Second-Order Cumulant Approach.
AB - Second-order cumulant expansion of the time dependent reduced density matrix has
been employed to evaluate hole hopping rates in pentacene, tetracene, picene, and
rubrene homodimers. The cumulant expansion is a full quantum mechanical approach,
which enables the use of the whole set of nuclear coordinates in computations and
the inclusion of both the effects of the equilibrium position displacements and
of normal mode mixing upon hole transfer. The time dependent populations
predicted by cumulant approach are in good agreement with those obtained by
numerical solution of time dependent Schrodinger equation, even for ultrafast
processes, where the Fermi Golden Rule fails.
PMID- 29345938
TI - PSO Method for Fitting Analytic Potential Energy Functions. Application to I
(H2O).
AB - In this work a particle swarm optimization (PSO) algorithm was used to fit an
analytic potential energy function to I-(H2O) intermolecular potential energy
curves calculated with DFT/B97-1 theory. The analytic function is a sum of two
body terms, each written as a generalized sum of Buckingham and Lennard-Jones
terms with only six parameters. Two models were used to describe the two-body
terms between I- and H2O: a three-site model H2O and a four-site model including
a ghost atom. The fits are compared with those obtained with a genetic/nonlinear
least-squares algorithm. The ghost atom model significantly improves the fitting
accuracy for both algorithms. The PSO fits are significantly more accurate and
much less time-consuming than those obtained with the genetic/nonlinear least
squares algorithm. Eight I----H2O potential energy curves, fit with the PSO
algorithm for the three- and four-site models, have RMSE of 1.37 and 0.22
kcal/mol and compute times of ~20 and ~68 min, respectively. The PSO fit for the
four-site model is quite adequate for determining densities of states and
partition functions for I-(H2O) n clusters at high energies and temperatures,
respectively. The PSO algorithm was also applied to the eight potential energy
curves, with the four-site model, for a short time ~8 min fitting. The RMSE was
small, only 0.37 kcal/mol, showing the high efficiency of the PSO algorithm with
retention of a good fitting accuracy. The PSO algorithm is a good choice for
fitting analytic potential energy functions, and for the work presented here was
able to find an adequate fit to an I-(H2O) analytic intermolecular potential with
a small number of parameters.
PMID- 29345940
TI - Environment-Modulated Crystallization of Cu2O and CuO Nanowires by
Electrospinning and Their Charge Storage Properties.
AB - This article reports the synthesis of cuprous oxide (Cu2O) and cupric oxide (CuO)
nanowires by controlling the calcination environment of electrospun polymeric
nanowires and their charge storage properties. The Cu2O nanowires showed higher
surface area (86 m2 g-1) and pore size than the CuO nanowires (36 m2 g-1).
Electrochemical analysis was carried out in 6 M KOH, and both the electrodes
showed battery-type charge storage mechanism. The electrospun Cu2O electrodes
delivered high discharge capacity (126 mA h g-1) than CuO (72 mA h g-1) at a
current density of 2.4 mA cm-2. Electrochemical impedance spectroscopy
measurements show almost similar charge-transfer resistance in Cu2O (1.2 Omega)
and CuO (1.6 Omega); however, Cu2O showed an order of magnitude higher ion
diffusion. The difference in charge storage between these electrodes is
attributed to the difference in surface properties and charge kinetics at the
electrode. The electrode also shows superior cyclic stability (98%) and Coulombic
efficiency (98%) after 5000 cycles. Therefore, these materials could be
acceptable choices as a battery-type or pseudocapacitive electrode in asymmetric
supercapacitors.
PMID- 29345939
TI - Discovery of Alternative Producers of the Enediyne Antitumor Antibiotic C-1027
with High Titers.
AB - The potent cytotoxicity and unique mode of action make the enediyne antitumor
antibiotic C-1027 an exquisite drug candidate for anticancer chemotherapy.
However, clinical development of C-1027 has been hampered by its low titer from
the original producer Streptomyces globisporus C-1027. Here we report three new C
1027 alternative producers, Streptomyces sp. CB00657, CB02329, and CB03608, from
The Scripps Research Institute actinomycetes strain collection. Together with the
previously disclosed Streptomyces sp. CB02366 strain, four C-1027 alternative
producers with C-1027 titers of up to 11-fold higher than the original producer
have been discovered. The five C-1027 producers, isolated from distant geographic
locations, are distinct Streptomyces strains based on morphology and taxonomy.
Pulsed-field gel electrophoresis and Southern analysis of the five C-1027
producers reveal that their C-1027 biosynthetic gene clusters (BGCs) are all
located on giant plasmids of varying sizes. The high nucleotide sequence
similarity among the five C-1027 BGCs implies that they most likely have evolved
from a common ancestor.
PMID- 29345941
TI - Dual Signaling DNA Electrochemistry: An Approach To Understand DNA Interfaces.
AB - Electrochemical DNA biosensors composed of a redox marker modified nucleic acid
probe tethered to a solid electrode is a common experimental construct for
detecting DNA and RNA targets, proteins, inorganic ions, and even small
molecules. This class of biosensors generally relies on the binding-induced
conformational changes in the distance of the redox marker relative to the
electrode surface such that the charge transfer is altered. The conventional
design is to attach the redox species to the distal end of a surface-bound
nucleic acid strand. Here we show the impact of the position of the redox marker,
whether on the distal or proximal end of the DNA monolayer, on the DNA interface
electrochemistry. Somewhat unexpectedly, greater currents were obtained when the
redox molecules were located on the distal end of the surface-bound DNA
monolayer, notionally furthest away from the electrode, compared with currents
when the redox species were located on the proximal end, close to the electrode.
Our results suggest that a limitation in ion accessibility is the reason why
smaller currents were obtained for the redox markers located at the bottom of the
DNA monolayer. This understanding shows that to allow the quantification of the
amount of redox labeled target DNA strand that hybridizes to probe DNA
immobilized on the electrode surface, the redox species must be on the distal end
of the surface-bound duplex.
PMID- 29345942
TI - Highly Stereoselective 2-Oxonia-Cope Rearrangement: A Platform Enabling At-Will
Control of Regio-, Enantio-, and Diastereoselectivity in the Vinylogous Aldol
Reactions of Aldehydes.
AB - A distinctly different approach for the vinylogous aldolation of aldehydes is
described, which exploits 2-oxonia-Cope rearrangement reactions between two
readily available partners, a set of rationally designed chiral homoallylic
alcohol synthons and aldehydes, under simple conditions. In these processes,
chirality transfer from the former to the latter is nearly perfect, giving rise
to excellent enantio- and diastereoselectivity without the regioselectivity issue
associated with traditional vinylogous aldol reactions.
PMID- 29345944
TI - Correction to Nanoscale Control of Morphology in Fullerene-Based Electron
Conducting Buffers via Organic Vapor Phase Deposition.
PMID- 29345943
TI - Oxycyanation of Vinyl Ethers with 2,2,6,6-Tetramethyl-N-oxopiperidinium Enabled
by Electron Donor-Acceptor Complex.
AB - An efficient and mild oxycyanation of vinyl ethers with 2,2,6,6-tetramethyl-N
oxopiperidinium and TMSCN is described. The mechanistic studies indicated that
the formation of an electron donor-acceptor complex and subsequent single
electron-transfer process could be involved in the reaction.
PMID- 29345945
TI - Chitosan-Silica Hybrid Composites for Removal of Sulfonated Azo Dyes from Aqueous
Solutions.
AB - In this study, the influence of the chitosan immobilization method on the
properties of final hybrid materials was performed. Chitosan was immobilized on
the surface of mesoporous (ChS2) and fumed silica (ChS3) by physical adsorption
and the sol-gel method (ChS1). It was found that physical immobilization of
chitosan allows to obtain hybrid composites (ChS) with a homogeneous distribution
of polymer on the surface, relatively wide pores, and specific surface area of
about 170 m2/g, pHPZC = 5.7 for ChS3 and 356 m2/g and pHPZC = 6.0 for ChS2. The
microporous chitosan-silica material with a specific surface area of 600 m2/g and
a more negatively charged surface (pHPZC = 4.2) was obtained by the sol-gel
reaction. The mechanisms of azo dye adsorption were studied, and the correlation
with the composite structure was distinguished. The generalized Langmuir equation
and its special cases, that is, Langmuir-Freundlich and Langmuir equations, were
applied for the analysis of adsorption isotherm data. The adsorption study showed
that physically adsorbed chitosan (ChS1 and ChS2) on a silica surface has a
higher sorption capacity, for example, 0.48 mmol/g for the acid red 88 (AR88) dye
(ChS2) and 0.23 mmol/g for the acid orange 8 (AO8) dye (ChS1), compared to the
composite obtained by the sol-gel method [ChS1, 0.05 mmol/g for the AO8 dye]. For
a deeper understanding of the behavior of immobilized chitosan in the adsorption
processes, various kinetic equations were applied: first-order, second-order,
mixed 1,2-order (MOE), multiexponential, and fractal-like MOE as well as
intraparticle and pore diffusion model equations. In the case of AO8 dye, the
adsorption rates were differentiated for three composites: for ChS3, 50% of the
dye was removed from the solution after merely 5 min and almost 90% after 80 min.
The slowest adsorption process controlled by the diffusion rate of dye molecules
into the internal space of the pore structure was found for ChS1 (225 min
halftime). In the case of ChS2, the rates for various dyes change in the
following order: acid orange (AO7) > orange G (OG) > acid red 1 (AR1) > AR88 >
AO8 (halftimes: 10.5 < 15.7 < 23.7 < 34.9 < 42.9 min).
PMID- 29345946
TI - Cooperative Metal-Ligand Catalyzed Intramolecular Hydroamination and
Hydroalkoxylation of Allenes Using a Stable Iron Catalyst.
AB - A new iron-catalyzed chemoselective intramolecular hydroamination and
hydroalkoxylation of the readily available alpha-allenic amines and alcohols to
valuable unsaturated 5-membered heterocycles, 2,3-dihydropyrrole and 2,3
dihydrofuran, is reported. Effective selectivity control is achieved by a metal
ligand cooperative activation of the substrates. The mild reaction conditions and
the use of low amounts of an air and moisture stable iron catalyst allow for the
hydrofunctionalization of a wide range of allenes bearing different functional
groups in good yields in the absence of base or any sensitive additives.
PMID- 29345947
TI - Nucleophilic Ring Opening of Donor-Acceptor Cyclopropanes Catalyzed by a Bronsted
Acid in Hexafluoroisopropanol.
AB - A general, Bronsted acid catalyzed method for the room temperature, nucleophilic
ring opening of donor-acceptor cyclopropanes in fluorinated alcohol solvent,
HFIP, is described. Salient features of this method include an expanded
cyclopropane scope, including those bearing single keto-acceptor groups and those
bearing electron-deficient aryl groups. Notably, the catalytic system proved
amenable to a wide range of nucleophiles including arenes, indoles, azides,
diketones, and alcohols.
PMID- 29345948
TI - Matched Coupling of Propargylic Carbonates with Cyclopropanols.
AB - The ring opening-coupling reaction of cyclopropanols with propargylic carbonates
affording synthetically attractive allenyl ketones has been developed. The
mechanism involves the ligand-exchange reaction of in situ formed allenyl
palladium methoxide with cyclopropanols followed by carbon-carbon bond cleavage
and reductive elimination. The reactions proceeded smoothly under mild reaction
conditions with Pd(0)/XPhos catalysis in the absence of any external base and
displayed a wide scope and application to a steroidal skeleton. The efficiency of
chirality transfer and synthetic utility of the allene products have also been
demonstrated.
PMID- 29345949
TI - Surface State Dynamics Dictating Transport in InAs Nanowires.
AB - Because of their high aspect ratio, nanostructures are particularly susceptible
to effects from surfaces such as slow electron trapping by surface states.
However, nonequilibrium trapping dynamics have been largely overlooked when
considering transport in nanoelectronic devices. In this study, we demonstrate
the profound influence of dynamic trapping processes on transport in InAs
nanowires through an investigation of the hysteretic and time-dependent behavior
of the transconductance. We observe large densities (~1013 cm-2) of slow surface
traps and demonstrate the ability to control and permanently fix their occupation
and charge through electrostatic manipulation by the gate potential followed by
thermal deactivation by cryogenic cooling. Furthermore, we observe a transition
from enhancement- to depletion-mode and a 400% change in field-effect mobility
within the same device when the initial gate voltage and sweep rate are varied,
revealing the severe impact of electrostatic history and dynamics on InAs
nanowire field-effect transistors. A time-dependent model for nanowire
transconductance based on nonequilibrium carrier population dynamics with
thermally activated capture and emission was constructed and showed excellent
agreement with experiments, confirming the effects to be a direct result of the
dynamics of slow surface traps characterized by large thermal activation barriers
(~ 700 meV). This work reveals a clear and direct link between the electrical
conductivity and the microscopic interactions of charged species with nanowire
surfaces and highlights the necessity for considering dynamic properties of
surface states in nanoelectronic devices.
PMID- 29345950
TI - Confined Electroconvective Vortices at Structured Ion Exchange Membranes.
AB - In this paper, we investigate electroconvective ion transport at cation exchange
membranes with different geometry square-wave structures (line undulations)
experimentally and numerically. Electroconvective microvortices are induced by
strong concentration polarization once a threshold potential difference is
applied. The applied potential required to start and sustain electroconvection is
strongly affected by the geometry of the membrane. A reduction in the resistance
of approximately 50% can be obtained when the structure size is similar to the
mixing layer (ML) thickness, resulting in confined vortices with less lateral
motion compared to the case of flat membranes. From electrical, flow, and
concentration measurements, ion migration, advection, and diffusion are
quantified, respectively. Advection and migration are dominant in the vortex ML,
whereas diffusion and migration are dominant in the stagnant diffusion layer.
Numerical simulations, based on Poisson-Nernst-Planck and Navier-Stokes
equations, show similar ion transport and flow characteristics, highlighting the
importance of membrane topology on the resulting electrokinetic and
electrohydrodynamic behavior.
PMID- 29345951
TI - Visible-Light-Driven Silver-Catalyzed One-Pot Approach: A Selective Synthesis of
Diaryl Sulfoxides and Diaryl Sulfones.
AB - An efficient one-pot approach for the synthesis of diaryl sulfoxides and diaryl
sulfones using aryl thiols and aryl diazonium salts was developed. The use of a
visible-light-driven silver catalysis and the subsequent singlet-oxygen-induced
oxidation enabled selective synthesis of sulfoxides and sulfones in the absence
of a photocatalyst. The reactions were carried out under mild reaction
conditions; the desired products were obtained under air atmosphere at room
temperature.
PMID- 29345952
TI - Visible-Light-Enabled Preparation of Palladium Nanoparticles and Application as
Catalysts for Suzuki-Miyaura Coupling.
AB - Silyl ketones were used for the preparation of palladium nanoparticles (PdNPs)
starting with Pd(OAc)2 in dimethylformamide under irradiation with a visible
light-emitting diode (LED). Variation of the silyl ketone structure allowed
adjustment of the PdNP diameter (1.9 or 5.2 nm). The in situ-formed PdNPs were
further stabilized with polyvinylpyrrolidone and then applied as recyclable
catalysts in the Suzuki-Miyaura coupling of arylboronic acids with aryl iodides
to obtain substituted biphenyls in excellent yields.
PMID- 29345953
TI - Micro to Nanoscale Engineering of Surface Precipitates Using Reconfigurable
Contact Lines.
AB - Nanoscale engineering has traditionally adopted the chemical route of synthesis
or optochemical techniques such as lithography requiring large process times,
expensive equipment, and an inert environment. Directed self-assembly using
evaporation of nanocolloidal droplet can be a potential low-cost alternative
across various industries ranging from semiconductors to biomedical systems. It
is relatively simple to scale and reorient the evaporation-driven internal flow
field in an evaporating droplet which can direct dispersed matter into functional
agglomerates. The resulting functional precipitates not only exhibit
macroscopically discernible changes but also nanoscopic variations in the
particulate assembly. Thus, the evaporating droplet forms an autonomous system
for nanoscale engineering without the need for external resources. In this
article, an indigenous technique of interfacial re-engineering, which is both
simple and inexpensive to implement, is developed. Such re-engineering widens the
horizon for surface patterning previously limited by the fixed nature of the
droplet interface. It involves handprinting hydrophobic lines on a hydrophilic
substrate to form a confinement of any selected geometry using a simple document
stamp. Droplets cast into such confinements get modulated into a variety of
shapes. The droplet shapes control the contact line behavior, evaporation
dynamics, and complex internal flow pattern. By exploiting the dynamic interplay
among these variables, we could control the deposit's macro- as well as nanoscale
assembly not possible with simple circular droplets. We provide a detailed
mechanism of the coupling at various length scales enabling a predictive
capability in custom engineering, particularly useful in nanoscale applications
such as photonic crystals.
PMID- 29345954
TI - Irradiation-Induced Palladium-Catalyzed Decarboxylative Heck Reaction of
Aliphatic N-(Acyloxy)phthalimides at Room Temperature.
AB - It is reported that Pd(PPh3)2Cl2 in combination with 4,5-bis(diphenylphosphino)
9,9-dimethylxanthene (Xantphos) under irradiation of blue LEDs efficiently
catalyzes a decarboxylative Heck reaction of vinyl arenes and vinyl heteroarenes
with aliphatic N-(acyloxy)phthalimides at room temperature. A broad scope of
secondary, tertiary, and quaternary carboxylates, including alpha-amino acid
derived esters, can be applied as amenable substrates with high
stereoselectivity. The experimental observation was explained by excitation-state
reactivity of the palladium complex under irradiation to induce single-electron
transfer to activate N-(acyloxy)phthalimides, and to suppress undesired beta
hydride elimination of alkyl palladium intermediates.
PMID- 29345955
TI - Investigation of Polymer/Surfactant Interactions and Their Impact on Itraconazole
Solubility and Precipitation Kinetics for Developing Spray-Dried Amorphous Solid
Dispersions.
AB - Methods were developed to systematically screen different polymer-surfactant
combinations for the purpose of enhancing amorphous active pharmaceutical
ingredient (API) solubility while maintaining its physical stability.
Itraconazole (ITZ) was chosen as the model API mostly due to its low aqueous
solubility. Special attention was paid to determine the effect of a reduction in
the critical micelle concentration (CMC) by specific polymer/surfactant
combinations on the ITZ solubility and physical stability. However, only a slight
correlation was actually found. Only the polymer/surfactant combinations with the
smallest effect on CMC improved solubility and stability of ITZ in simulated
intestinal fluids (SIF). Surfactants were found to negate the stabilizing effects
of polymers. ITZ crystallization tendency generally depended on the degree of
supersaturation and the type of polymer/surfactant combinations used. In general,
we found that instead of focusing solely on reducing the CMC, a systematic
screening of systems that maintain high ITZ supersaturation proved to be a
successful approach.
PMID- 29345956
TI - Measuring Three-Dimensional Strain and Structural Defects in a Single InGaAs
Nanowire Using Coherent X-ray Multiangle Bragg Projection Ptychography.
AB - III-As nanowires are candidates for near-infrared light emitters and detectors
that can be directly integrated onto silicon. However, nanoscale to microscale
variations in structure, composition, and strain within a given nanowire, as well
as variations between nanowires, pose challenges to correlating microstructure
with device performance. In this work, we utilize coherent nanofocused X-rays to
characterize stacking defects and strain in a single InGaAs nanowire supported on
Si. By reconstructing diffraction patterns from the 2110 Bragg peak, we show that
the lattice orientation varies along the length of the wire, while the strain
field along the cross-section is largely unaffected, leaving the band structure
unperturbed. Diffraction patterns from the 0110 Bragg peak are reproducibly
reconstructed to create three-dimensional images of stacking defects and
associated lattice strains, revealing sharp planar boundaries between different
crystal phases of wurtzite (WZ) structure that contribute to charge carrier
scattering. Phase retrieval is made possible by developing multiangle Bragg
projection ptychography (maBPP) to accommodate coherent nanodiffraction patterns
measured at arbitrary overlapping positions at multiple angles about a Bragg
peak, eliminating the need for scan registration at different angles. The
penetrating nature of X-ray radiation, together with the relaxed constraints of
maBPP, will enable the in operando imaging of nanowire devices.
PMID- 29345957
TI - Besifloxacin: A Critical Review of Its Characteristics, Properties, and
Analytical Methods.
AB - Bacterial conjunctivitis has high impact on the health of the population, since
it represents more than a third of ocular pathologies reported by health services
worldwide. There is a high incidence of bacterial resistance to the
antimicrobials most commonly used for the treatment of conjunctivitis. In this
context, besifloxacin stands out, since it is a fluoroquinolone developed
exclusively for topical ophthalmic use, presenting a low risk of developing
resistance due to its reduced systemic exposure. Bausch & Lomb markets it as
ophthalmic suspension, under the trade name BesivanceTM. Literature review on
besifloxacin is presented, covering its pharmaceutical and clinical
characteristics, and the analytical methods used to measure the drug in
pharmaceutical products and biological samples. High performance liquid
chromatography is the most used method for this purpose. A discussion on Green
Chemistry is also presented, focusing the importance of the development of green
analytical methods for the analysis of drugs.
PMID- 29345958
TI - Plasma Cell Variant Multicentric Castleman Disease and Kaposi's Sarcoma in a
Treatment-Naive HIV-Infected Patient.
PMID- 29345959
TI - Have We Not Learned from Past Mistakes?
PMID- 29345960
TI - Pacing strategies by age in marathon cross-country skiing.
AB - OBJECTIVES: Pacing strategies have mainly been investigated for runners, but
little is known for cross-country skiers. The aim of the present study was to
investigate whether differences in pacing strategies do exist between younger and
older cross-country skiers competing in the 42 km 'Engadin Ski Marathon'.
METHODS: Pacing was studied in 105,565 cross-country skiers (classified in 5-year
age groups) competing between 1998 and 2016 in this race by examining changes of
mean section velocity in 10 km (Change A, i.e. 100*(velocity in the 10-20 km
section - velocity in the 0-10 km section)/velocity in the 0-10 km section), 20
km (Change B) and 35 km (Change C). RESULTS: A small sex*distance (i.e. Change A
versus Change B versus Change C) interaction on change of velocity was shown (P <
.001, eta2 = 0.016), with women showing a less even pacing than men. In women,
there was a trivial main effect of age group on Change A (P < .001, eta2 = 0.008)
with a smaller decrease in velocity in age group <20 (-7.4%) and larger decrease
in velocity in age group 75-79 (-12.8%), and Change B (P = .006, eta2 = 0.004)
with smaller increase in velocity in age group 75-79 (+30.6%) and larger increase
in velocity in age group 40-44 (+37.7%), but not on Change C (P = .784, eta2 =
0.003). In men, a small main effect of age group on Change A was shown (P < .001,
eta2 = 0.019), with a smaller decrease of velocity in age group <20 (-3.5%) and
larger in age group 70-74 (-10.5%). Trivial main effects of age group on Change B
(P < .001, eta2 = .002), with a smaller increase of velocity in age group 85-89
(+25.8%) and larger increase in age group 70-74 (+33.0%), and Change C (P < .001,
eta2 = 0.003), with smaller decrease of velocity in age group 85-89 (-38.2%) and
larger decrease in age group 80-84 (-41.0%), were found. CONCLUSIONS: Based on
these findings, it was concluded that men and young cross-country skiers had a
more even pacing than women and older cross-country skiers, which was in contrast
with previous findings in other endurance sports, suggesting that the sex- and
age-related differences in pacing might be sport-dependent.
PMID- 29345961
TI - Effects of Quercetin, Kaempferol, and Exogenous Glutathione on Phospho- and Total
AKT in 3T3-L1 Preadipocytes.
AB - Obesity has been reported to be a risk factor for some types of cancer, such as
prostate and lung. The AKT or PI3K-AKT is a signal transduction pathway that
promotes survival and growth in response to extracellular signals. The aim of
this study was to investigate the effects of two flavonoids, quercetin and
kaempferol, and exogenous glutathione (GSH) on the expressions of phospho- and
total-AKT levels in 3T3-L1 preadipocytes. Glyceraldehyde 3-phosphate
dehydrogenase (GAPDH) levels were measured in the treated samples and used as the
internal standard. 3T3-L1 preadipocytes were exposed to each flavonoid and GSH at
concentrations of 0, 5, 10, 15, 20, and 25 uM, and the levels of phospho- and
total-Akt were measured by the MILLIPLEX MAP mates protocol, based on the Luminex
xMAP technology (Millipore Corp., St. Charles, MI, USA). GAPDH levels in the
preadipocytes were not significantly different at the doses tested for the
flavonoids and exogenous GSH. However, significant (p <.05) decreases in phospho
AKT levels in cells treated with quercetin, kaempferol, and GSH at certain doses
were observed compared to their respective controls. Total-AKT levels showed the
same profile for all the tested compounds. Significant (p <.01) differences were
observed for kaempferol (15-25 uM), quercetin at 10 and 20 uM, and GSH at 10 uM
compared to their respective controls. Findings suggest that exposure of 3T3-L1
preadipocytes to quercetin, kaempferol, and GSH may block the activation of AKT,
suggesting the role such compounds play in cell differentiation in 3T3-L1 cells.
PMID- 29345962
TI - Role of selected polymorphisms in determining muscle fiber composition in
Japanese men and women.
AB - Genetic polymorphisms and sex differences are suggested to affect muscle fiber
composition; however, no study has investigated the effects of genetic
polymorphisms on muscle fiber composition with respect to sex differences.
Therefore, the present study examined the effects of genetic polymorphisms on
muscle fiber composition with respect to sex differences in the Japanese
population. The present study included 211 healthy Japanese individuals (102 men
and 109 women). Muscle biopsies were obtained from the vastus lateralis to
determine the proportion of myosin heavy chain (MHC) isoforms (MHC-I, MHC-IIa,
and MHC-IIx). Moreover, we analyzed polymorphisms in alpha-actinin-3 gene (
ACTN3; rs1815739 ), angiotensin-converting enzyme gene ( ACE; rs4341 ), hypoxia
inducible factor 1 alpha gene ( rs11549465 ), vascular endothelial growth factor
receptor 2 gene ( rs1870377 ), and angiotensin II receptor, type 2 gene (
rs11091046 ), by TaqMan single-nucleotide polymorphism genotyping assays. The
proportion of MHC-I was 9.8% lower in men than in women, whereas the proportion
of MHC-IIa and MHC-IIx was higher in men than in women (5.0 and 4.6%,
respectively). Men with the ACTN3 RR + RX genotype had a 4.8% higher proportion
of MHC-IIx than those with the ACTN3 XX genotype. Moreover, men with the ACE ID +
DD genotype had a 4.7% higher proportion of MHC-I than those with the ACE II
genotype. Furthermore, a combined genotype of ACTN3 R577X and ACE
insertion/deletion (I/D) was significantly correlated with the proportion of MHC
I ( r = -0.23) and MHC-IIx ( r = 0.27) in men. In contrast, no significant
correlation was observed between the examined polymorphisms and muscle fiber
composition in women. These results suggest that the ACTN3 R577X and ACE I/D
polymorphisms independently affect the proportion of human skeletal muscle fibers
MHC-I and MHC-IIx in men but not in women. NEW & NOTEWORTHY In men, the RR + RX
genotype of the alpha-actinin-3 gene ( ACTN3) R577X polymorphism was associated
with a higher proportion of myosin heavy chain (MHC)-IIx. The ID + DD genotype of
the angiotensin-converting enzyme gene ( ACE) insertion/deletion (I/D)
polymorphism, in contrast to a previous finding, was associated with a higher
proportion of MHC-I in men. In addition, the combined genotype of these
polymorphisms was correlated with the proportion of MHC-I and MHC-IIx in men.
Thus ACTN3 R577X and ACE I/D polymorphisms influence the muscle fiber composition
in Japanese men.
PMID- 29345963
TI - Deletion of estrogen receptor alpha in skeletal muscle results in impaired
contractility in female mice.
AB - Estradiol deficiency in females can result in skeletal muscle strength loss, and
treatment with estradiol mitigates the loss. There are three primary estrogen
receptors (ERs), and estradiol elicits effects through these receptors in various
tissues. Ubiquitous ERalpha-knockout mice exhibit numerous biological disorders,
but little is known regarding the specific role of ERalpha in skeletal muscle
contractile function. The purpose of this study was to determine the impact of
skeletal muscle-specific ERalpha deletion on contractile function, hypothesizing
that ERalpha is a main receptor through which estradiol affects muscle strength
in females. Deletion of ERalpha specifically in skeletal muscle (skmERalphaKO)
did not affect body mass compared with wild-type littermates (skmERalphaWT) until
26 wk of age, at which time body mass of skmERalphaKO mice began to increase
disproportionally. Overall, skmERalphaKO mice had low strength demonstrated in
multiple muscles and by several contractile parameters. Isolated extensor
digitorum longus muscles from skmERalphaKO mice produced 16% less eccentric and
16-26% less submaximal and maximal isometric force, and isolated soleus muscles
were more fatigable, with impaired force recovery relative to skmERalphaWT mice.
In vivo maximal torque productions by plantarflexors and dorsiflexors were 16%
and 12% lower in skmERalphaKO than skmERalphaWT mice, and skmERalphaKO muscles
had low phosphorylation of myosin regulatory light chain. Plantarflexors also
generated 21-32% less power, submaximal isometric and peak concentric torques.
Data support the hypothesis that ablation of ERalpha in skeletal muscle results
in muscle weakness, suggesting that the beneficial effects of estradiol on muscle
strength are receptor mediated through ERalpha. NEW & NOTEWORTHY We
comprehensively measured in vitro and in vivo skeletal muscle contractility in
female estrogen receptor alpha (ERalpha) skeletal muscle-specific knockout mice
and report that force generation is impaired across multiple parameters. These
results support the hypothesis that a primary mechanism through which estradiol
elicits its effects on strength is mediated by ERalpha. Evidence is presented
that estradiol signaling through ERalpha appears to modulate force at the
molecular level via posttranslational modifications of myosin regulatory light
chain.
PMID- 29345965
TI - The case for exploring the usage of employee wellness programs for pediatric
asthma control.
AB - The multiple socioecological determinants of asthma mandate that pediatricians
develop a treatment strategy beyond the practice-based setting. To expand to a
more impactful community-based role, pediatricians must look to form partnerships
with groups that are capable of promoting social and environmental change.
Traditionally, these groups have included schools, governmental agencies, and
child care establishments. One group that is not actively being availed of are
employers who have shown success in improving adult-based outcomes through
wellness programs. Employers are stakeholders in pediatric asthma care through
its impact on reduced worker productivity and higher health insurance premiums.
An employer's focus on pediatric asthma will be a collective win for the employer
and employee. The article herein describes the rationale for the focus of
employers on pediatric asthma care and potential incorporation within employer
based wellness strategies.
PMID- 29345966
TI - No Room for Error in Medicine-A Case of Deja Vu.
PMID- 29345967
TI - Reclassifying Acute Respiratory Distress Syndrome.
AB - RATIONALE: The ratio of PaO2 to FiO2 (P/F) defines acute respiratory distress
syndrome (ARDS) severity and suggests appropriate therapies. OBJECTIVES: We
investigated 1) whether a 150-mm-Hg P/F threshold within the range of moderate
ARDS (100-200 mm Hg) would define two subgroups that were more homogeneous; and
2) which criteria led the clinicians to apply extracorporeal membrane oxygenation
(ECMO) in severe ARDS. METHODS: At the 150-mm-Hg P/F threshold, moderate patients
were split into mild-moderate (n = 50) and moderate-severe (n = 55) groups.
Patients with severe ARDS (FiO2 not available in three patients) were split into
higher (n = 63) and lower (n = 18) FiO2 groups at an 80% FiO2 threshold.
MEASUREMENTS AND MAIN RESULTS: Compared with mild-moderate ARDS, patients with
moderate-severe ARDS had higher peak pressures, PaCO2, and pH. They also had
heavier lungs, greater inhomogeneity, more noninflated tissue, and greater lung
recruitability. Within 84 patients with severe ARDS (P/F < 100 mm Hg), 75%
belonged to the higher FiO2 subgroup. They differed from the patients with severe
ARDS with lower FiO2 only in PaCO2 and lung weight. Forty-one of 46 patients
treated with ECMO belonged to the higher FiO2 group. Within this group, the
patients receiving ECMO had higher PaCO2 than the 22 non-ECMO patients. The
inhomogeneity ratio, total lung weight, and noninflated tissue were also
significantly higher. CONCLUSIONS: Using the 150-mm-Hg P/F threshold gave a more
homogeneous distribution of patients with ARDS across the severity subgroups and
identified two populations that differed in their anatomical and physiological
characteristics. The patients treated with ECMO belonged to the severe ARDS
group, and almost 90% of them belonged to the higher FiO2 subgroup.
PMID- 29345968
TI - Mature gastric chief cells are not required for the development of metaplasia.
AB - During human gastric carcinogenesis, intestinal metaplasia is frequently seen in
the atrophic stomach. In mice, a distinct type of metaplasia known as spasmolytic
polypeptide-expressing metaplasia (SPEM) is found in several inflammatory and
genetically engineered models. Given the diversity of long- and short-term models
of mouse SPEM, it remains unclear whether all models have a shared or distinct
molecular mechanism. The origin of SPEM in mice is presently under debate. It is
postulated that stem or progenitor cells acquire genetic alterations that then
supply metaplastic cell clones, whereas the possibility of transdifferentiation
or dedifferentiation from mature gastric chief cells has also been suggested. In
this study, we report that loss of chief cells was sufficient to induce short
term regenerative SPEM-like lesions that originated from chief cell precursors in
the gastric neck region. Furthermore, Lgr5+ mature chief cells failed to
contribute to both short- and long-term metaplasia, whereas isthmus stem and
progenitor cells efficiently contributed to long-term metaplasia. Interestingly,
multiple administrations of high-dose pulsed tamoxifen induced expansion of Lgr5
expression and Lgr5-CreERT recombination within the isthmus progenitors apart
from basal chief cells. Thus we conclude that short-term SPEM represents a
regenerative process arising from neck progenitors following chief cell loss,
whereas true long-term SPEM originates from isthmus progenitors. Mature gastric
chief cells may be dispensable for SPEM development. NEW & NOTEWORTHY Recently,
dedifferentiation ability in gastric chief cells during metaplasia development
has been proposed. Our findings reveal that lesions that were thought to be acute
metaplasia in fact represent normal regeneration supplied from neck lineage and
that isthmus stem/progenitors are more responsible for sustained metaplastic
changes. Cellular plasticity in gastric chief cells may be more limited than
recently highlighted.
PMID- 29345964
TI - Immune Response to Dengue and Zika.
AB - Flaviviruses such as dengue (DENV), yellow fever (YFV), West Nile (WNV), and Zika
(ZIKV) are human pathogens of global significance. In particular, DENV causes the
most prevalent mosquito-borne viral diseases in humans, and ZIKV emerged from
obscurity into the spotlight in 2016 as the etiologic agent of congenital Zika
syndrome. Owing to the recent emergence of ZIKV as a global pandemic threat, the
roles of the immune system during ZIKV infections are as yet unclear. In
contrast, decades of DENV research implicate a dual role for the immune system in
protection against and pathogenesis of DENV infection. As DENV and ZIKV are
closely related, knowledge based on DENV studies has been used to prioritize
investigation of ZIKV immunity and pathogenesis, and to accelerate ZIKV
diagnostic, therapeutic, and vaccine design. This review discusses the following
topics related to innate and adaptive immune responses to DENV and ZIKV: the
interferon system as the key mechanism of host defense and viral target for
immune evasion, antibody-mediated protection versus antibody-dependent
enhancement, and T cell-mediated protection versus original T cell antigenic sin.
Understanding the mechanisms that regulate the balance between immune-mediated
protection and pathogenesis during DENV and ZIKV infections is critical toward
development of safe and effective DENV and ZIKV therapeutics and vaccines.
PMID- 29345969
TI - Reply to Dahm et al., to Shah et al., and to Schunemann and Brozek.
PMID- 29345971
TI - A Blast from the Past-Back to the 1970s.
PMID- 29345970
TI - The Prevalence and Significance of Staphylococcus aureus in Patients with Non
Cystic Fibrosis Bronchiectasis.
AB - RATIONALE: Staphylococcus aureus is commonly cultured from the sputum of patients
with bronchiectasis; however, little is known about the prevalence of the
organism in these patients, the characteristics of patients who have grown the
organism, or its implications. OBJECTIVES: Determine the relationship between S.
aureus and pulmonary function, frequency of exacerbations, and frequency of
hospitalization in patients with bronchiectasis Methods: The Bronchiectasis
Research Registry is a database of adults with non-cystic fibrosis bronchiectasis
identified from 13 sites within the United States. Baseline and follow-up
demographic, spirometric, microbiologic, and therapeutic data were entered into a
central web-based database. Patients were grouped into three cohorts based on
their previous respiratory cultures at the time of entry into the Registry: 1) no
prior S. aureus or glucose-nonfermenting gram-negative bacilli (NF-GNB)
(Pseudomonas, Stenotrophomonas, or Burkholderia spp.); 2) prior S. aureus at
least once; or 3) no prior S. aureus but prior NF-GNB at least once. The
association between S. aureus isolation and pulmonary function and frequency of
exacerbations and hospital admissions was assessed, both at baseline and after 1
year of follow-up. RESULTS: S. aureus was cultured from 94 of 830 patients
(11.3%) included in the analysis. Patients who had grown S. aureus before entry
into the Registry had a frequency of prior exacerbations and baseline pulmonary
function that was between that of patients who had grown NF-GNB and those who had
grown neither NF-GNB or S. aureus. Similarly, at the first follow-up visit after
study entry, patients who had grown S. aureus had a frequency of exacerbations
and hospitalizations that was between those of patients who had grown NF-GNB and
those who had grown neither NF-GNB nor S. aureus. However, in multivariate
analysis, S. aureus was not associated with pulmonary function, frequency of
exacerbation, or hospital admissions. There were no significant differences in
patient characteristics or outcomes between patients who had methicillin
sensitive and methicillin-resistant S. aureus. CONCLUSIONS: Staphylococcus aureus
does not appear to be an independent risk factor for severe disease in patients
with bronchiectasis enrolled in the Bronchiectasis Research Registry.
PMID- 29345972
TI - Trypsin Inhibitors from Cajanus cajan and Phaseolus limensis Possess Antioxidant,
Anti-Inflammatory, and Antibacterial Activity.
AB - Protease inhibitors are one of the most promising and investigated subjects for
their role in pharmacognostic and pharmacological studies. This study aimed to
investigate antioxidant, anti-inflammatory, and antimicrobial activities of
trypsin inhibitors (TIs) from two plant sources (Cajanus cajan and Phaseolus
limensis). TI was purified from C. cajan (PUSA-992) by ammonium sulfate
precipitation followed by ion exchange chromatography. TI from Phaseolus limensis
(lima bean trypsin inhibitor; LBTI) was procured from Sigma-Aldrich, St. Louis,
Missouri, United States. The antioxidant activity was analyzed by ferric ion
reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH). The
anti-inflammatory property of TIs was determined by inhibition of albumin
denaturation assay. Ascorbic acid and aspirin were used as standards for
antioxidant and anti-inflammatory assays, respectively. These TIs were tested
against various bacterial and fungal strains. The TIs showed DPPH radical
scavenging activity in a concentration-dependent manner with IC50 values
comparable to ascorbic acid. The FRAP values were also observed comparable to
ascorbic acid and followed the trend of dose-dependent manner. The half maximal
inhibitory concentration (IC50) values of CCTI and LBTI in anti-inflammatory test
showed that LBTI is more potent than CCTI. The TIs showed potent antibacterial
activity, but apparently no action against fungi. This study has reported the
biological properties of CCTI and LBTI for the first time. The results show that
TIs possess the ability to inhibit diseases caused by oxidative stress,
inflammation, and bacterial infestation.
PMID- 29345973
TI - R-Spondin-2 Is Upregulated in Idiopathic Pulmonary Fibrosis and Affects
Fibroblast Behavior.
AB - Idiopathic pulmonary fibrosis (IPF) is characterized by the expansion of the
myofibroblast population, excessive extracellular matrix accumulation, and
destruction of the lung parenchyma. The R-spondin family (RSPO) comprises a group
of proteins essential for development. Among them, RSPO2 is expressed primarily
in the lungs, and its mutations cause severe defects in the respiratory tract.
Interestingly, RSPO2 participates in the canonical Wingless/int1 pathway, a
critical route in the pathogenesis of IPF. Thus, the aim of this study was to
examine the expression and putative role of RSPO2 in this disease. We found that
RSPO2 and its receptor leucine-rich G protein-coupled receptor 6 were upregulated
in IPF lungs, where they localized primarily in fibroblasts and epithelial cells.
Stimulation of IPF and normal lung fibroblasts with recombinant human RSPO2
resulted in the deregulation of numerous genes, although the transcriptional
response was essentially distinct. In IPF fibroblasts, RSPO2 stimulation induced
the up- or downregulation of several genes involved in the Wingless/int1 pathway
(mainly from noncanonical signaling). In both normal and IPF fibroblasts, RSPO2
modifies the expression of genes implicated in several pathways, including the
cell cycle and apoptosis. In accordance with gene expression, the stimulation of
normal and IPF fibroblasts with RSPO2 significantly reduced cell proliferation
and induced cell death. RSPO2 also inhibited collagen production and increased
the expression of matrix metalloproteinase 1. Silencing RSPO2 with shRNA induced
the opposite effects. Our findings demonstrate, for the first time to our
knowledge, that RSPO2 is upregulated in IPF, where it appears to have an
antifibrotic role.
PMID- 29345974
TI - Cognitive Effects of Cancer and Cancer Treatments.
AB - As the population of cancer survivors has grown into the millions, there has been
increasing emphasis on understanding how the late effects of treatment affect
survivors' ability to return to work/school, their capacity to function and live
independently, and their overall quality of life. This review focuses on
cognitive change associated with cancer and cancer treatments. Research in this
area has progressed from a pharmacotoxicology perspective to a view of the
cognitive change as a complex interaction of aspects of the treatment,
vulnerability factors that increase risk for posttreatment cognitive decline,
cancer biology, and the biology of aging. Methodological advances include the
development of (a) measurement approaches that assess more fine-grained
subcomponents of cognition based on cognitive neuroscience and (b) advanced
statistical approaches. Conceptual issues that arise from this multidimensional
perspective are described in relation to future directions, understanding of
mechanisms, and development of innovative interventions.
PMID- 29345975
TI - Nano- and micro-particles for delivery of catechins: Physical and biological
performance.
AB - Catechins, present in many fruits and vegetables, have many health benefits, but
they are prone to degradation. Nano- and micro-particle systems have been used to
stabilise catechins when exposed to adverse environments and to improve their
bioavailability after ingestion. This review discusses the inherent properties of
various catechins, the design of delivery formulations and the properties of
catechin-loaded nano- and micro-particles. The protection afforded to catechins
during exposure to harsh environmental conditions and gastrointestinal tract
transit is reviewed. The bioavailability and efficacy of encapsulated catechins,
as assessed by various in vitro and in vivo conditions, are discussed.
Bioavailability based on uptake in the upper gut alone underestimates the
bioavailability as polyphenols. The caveats with interpretation of
bioavailability based on various tests are discussed, when taking into
consideration the pathways of catechin metabolism including the role of the gut
microflora. However, taken together, the weight of the evidence suggests that
there are potentially improved health benefits with the use of appropriately
designed nano- and micro-particles for delivery of catechins. Further systematic
studies on the metabolism and physiological effects of encapsulated catechins in
vivo and clinical trials are needed to validate the bioefficacy of the
encapsulated catechins.
PMID- 29345976
TI - Synthetic Biology: Immunotherapy by Design.
AB - Cellular immunotherapy holds great promise for the treatment of human disease.
Clinical evidence suggests that T cell immunotherapies have the potential to
combat cancers that evade traditional immunotherapy. Despite promising results,
adverse effects leading to fatalities have left scientists seeking tighter
control over these therapies, which is reflected in the growing body of synthetic
biology literature focused on developing tightly controlled, context-independent
parts. In addition, researchers are adapting these tools for other uses, such as
for the treatment of autoimmune disease, HIV infection, and fungal interactions.
We review this body of work and devote special attention to approaches that may
lend themselves to the development of an "ideal" therapy: one that is safe,
efficient, and easy to manufacture. We conclude with a look toward the future of
immunotherapy: how synthetic biology can shift the paradigm from the treatment of
disease to a focus on wellness and human health as a whole.
PMID- 29345978
TI - Research in Rare Disease: From Genomics to Proteomics.
AB - Jessica Lacoste from the Donnelly Centre at the University of Toronto was awarded
best poster at the annual Society of Biomolecular Imaging and Informatics meeting
held in San Diego, September 2017. Her work focuses on characterizing the protein
localization of variants involved in rare disease. The current works and future
directions of research in rare disease are summarized in the following overview.
PMID- 29345979
TI - Machine Learning Enables Live Label-Free Phenotypic Screening in Three
Dimensions.
AB - There is a large amount of information in brightfield images that was previously
inaccessible by using traditional microscopy techniques. This information can now
be exploited by using machine-learning approaches for both image segmentation and
the classification of objects. We have combined these approaches with a label
free assay for growth and differentiation of leukemic colonies, to generate a
novel platform for phenotypic drug discovery. Initially, a supervised machine
learning algorithm was used to identify in-focus colonies growing in a three
dimensional (3D) methylcellulose gel. Once identified, unsupervised clustering
and principle component analysis of texture-based phenotypic profiles were
applied to group similar phenotypes. In a proof-of-concept study, we successfully
identified a novel phenotype induced by a compound that is currently in clinical
trials for the treatment of leukemia. We believe that our platform will be of
great benefit for the utilization of patient-derived 3D cell culture systems for
both drug discovery and diagnostic applications.
PMID- 29345977
TI - Targeted and Nontargeted alpha-Particle Therapies.
AB - alpha-Particle irradiation of cancerous tissue is increasingly recognized as a
potent therapeutic option. We briefly review the physics, radiobiology, and
dosimetry of alpha-particle emitters, as well as the distinguishing features that
make them unique for radiopharmaceutical therapy. We also review the emerging
clinical role of alpha-particle therapy in managing cancer and recent studies on
in vitro and preclinical alpha-particle therapy delivered by antibodies, other
small molecules, and nanometer-sized particles. In addition to their unique
radiopharmaceutical characteristics, the increased availability and improved
radiochemistry of alpha-particle radionuclides have contributed to the growing
recent interest in alpha-particle radiotherapy. Targeted therapy strategies have
presented novel possibilities for the use of alpha-particles in the treatment of
cancer. Clinical experience has already demonstrated the safe and effective use
of alpha-particle emitters as potent tumor-selective drugs for the treatment of
leukemia and metastatic disease.
PMID- 29345980
TI - Society of Biomolecular Imaging and Informatics High-Content Screening/High
Content Analysis Emerging Technologies in Biological Models, When and Why?
PMID- 29345981
TI - Correction to: J Endourol 2017;31:985-990.
PMID- 29345982
TI - Development of a Trio of Potential Biomarkers for Cancer Prognosis.
PMID- 29345983
TI - No Seat at the Recommendations Table?
PMID- 29345984
TI - Development of a Polymerase Chain Reaction/Ligase Detection Reaction Assay for
Detection of CYP2C19 Polymorphisms.
AB - AIMS: Cytochrome P450 2C19 (CYP2C19) genotypes are associated with differential
drug metabolism. The aim of this study was to establish a reliable assay for
CYP2C19 genotyping based on a polymerase chain reaction/ligase detection reaction
(PCR-LDR). MATERIALS AND METHODS: Specific primers and probes were designed to
detect CYP2C19*1, *2, *3, and *17. A control for each allele was prepared and
used for performance evaluation. A total of 200 clinical samples were analyzed
using the PCR-LDR assay and Sanger sequencing. RESULTS: The detection limit of
the PCR-LDR assay was 2 ng/MUL of genomic DNA. Common interfering substances in
the blood did not affect the results of the detection. For the clinical samples,
the results of the PCR-LDR and the Sanger sequencing were identical. Among the
200 patients, 104 (52%) were wild type (*1/*1), 64 (32%) were *1/*2, 16 (8%) were
*1/*3, 8 (4%) were *2/*2, 7 (3.5%) were *2/*3, and 1 (0.5%) was *1/*7. No *3/*3
genotype was detected in these patients. CONCLUSION: This PCR-LDR assay is
reliable for the detection of CYP2C19 genotypes in a clinical setting. It will be
a useful tool to screen for CYP2C19 loss-of-function alleles in patients before
clopidogrel and proton pump inhibitor treatment.
PMID- 29345985
TI - CYP3A Activity and Rivaroxaban Serum Concentrations in Russian Patients with Deep
Vein Thrombosis.
AB - BACKGROUND: Rivaroxaban is metabolized in the liver via CYP3A4, the cytochrome
involved in the metabolism of nearly 50% of all medications. Thus, its effective
concentration depends on multiple pharmacologic parameters. METHODS: The primary
goal of our research was to study the correlation between the CYP3A family
activity and the safety and efficacy of anticoagulant therapy with rivaroxaban in
patients with deep vein thrombosis (DVT). Thirty one patients with DVT aged 21-83
years, 18 men and 13 women, received rivaroxaban (Xarelto) 30 mg/day for 21 days
after diagnosis and 20 mg/day for the follow-up period of 6 months. During the
study period, Doppler ultrasound was performed weekly to assess the clot dynamics
and recanalization time. RESULTS: We found a direct statistically reliable
correlation between CYP3A4 activity and both peak and trough rivaroxaban levels.
A correlation was also found between the initial clot length and the time to full
recanalization r = 0.764 (0.554-0.883), p < 0.0001. No significant link was found
between either the glomerular filtration rate and peak rivaroxaban concentrations
or between CYP3A4 activity and the treatment effectiveness parameters. No
connection between renal function and rivaroxaban concentration was established
in our study, which agrees with the clinical trials data that allow unlimited
rivaroxaban use in patients with glomerular filtration rate >30 mL/min.
CONCLUSIONS: The direct link between the initial clot length and time to full
recanalization that has been found means that patients with more advanced stages
of thrombosis need more time to reach recanalization than their counterparts with
a less severe condition.
PMID- 29345986
TI - Vital Signs: Seismology of Icy Ocean Worlds.
AB - Ice-covered ocean worlds possess diverse energy sources and associated mechanisms
that are capable of driving significant seismic activity, but to date no
measurements of their seismic activity have been obtained. Such investigations
could reveal the transport properties and radial structures, with possibilities
for locating and characterizing trapped liquids that may host life and yielding
critical constraints on redox fluxes and thus on habitability. Modeling efforts
have examined seismic sources from tectonic fracturing and impacts. Here, we
describe other possible seismic sources, their associations with science
questions constraining habitability, and the feasibility of implementing such
investigations. We argue, by analogy with the Moon, that detectable seismic
activity should occur frequently on tidally flexed ocean worlds. Their ices
fracture more easily than rocks and dissipate more tidal energy than the <1 GW of
the Moon and Mars. Icy ocean worlds also should create less thermal noise due to
their greater distance and consequently smaller diurnal temperature variations.
They also lack substantial atmospheres (except in the case of Titan) that would
create additional noise. Thus, seismic experiments could be less complex and less
susceptible to noise than prior or planned planetary seismology investigations of
the Moon or Mars. Key Words: Seismology-Redox-Ocean worlds-Europa-Ice
Hydrothermal. Astrobiology 18, 37-53.
PMID- 29345987
TI - Habitable Worlds: Delivering on the Promises of Online Education.
AB - Critical thinking and scientific reasoning are central to higher education in the
United States, but many courses (in-person and online) teach students information
about science much more than they teach the actual process of science and its
associated knowledge and skills. In the online arena specifically, the tools
available for course construction exacerbate this problem by making it difficult
to build the types of active learning activities that research shows to be the
most effective. Here, we present a report on Habitable Worlds, offered by Arizona
State University for 12 semesters over the past 6 years. This is a unique online
course that uses an array of novel technologies to deliver an active, inquiry
driven learning experience. Learning outcomes and quantitative data from more
than 3000 students demonstrate the success of our approach but also identify
several remaining challenges. The design and development of this course offers
valuable lessons for instructional designers and educators who are interested in
fully capitalizing on the capabilities of 21st-century technology to achieve
educational goals. Key Words: Online education-Active learning-SETI-Astrobiology
Teaching. Astrobiology 17, 86-99.
PMID- 29345988
TI - Measuring Entropy in Molecular Recognition by Proteins.
AB - Molecular recognition by proteins is fundamental to the molecular basis of
biology. Dissection of the thermodynamic landscape governing protein-ligand
interactions has proven difficult because determination of various entropic
contributions is quite challenging. Nuclear magnetic resonance relaxation
measurements, theory, and simulations suggest that conformational entropy can be
accessed through a dynamical proxy. Here, we review the relationship between
measures of fast side-chain motion and the underlying conformational entropy. The
dynamical proxy reveals that the contribution of conformational entropy can range
from highly favorable to highly unfavorable and demonstrates the potential of
this key thermodynamic variable to modulate protein-ligand interactions. The
dynamical so-called entropy meter also refines the role of solvent entropy and
directly determines the loss in rotational-translational entropy that occurs upon
formation of high-affinity complexes. The ability to quantify the roles of
entropy through an entropy meter based on measurable dynamical properties
promises to highlight its role in protein function.
PMID- 29345989
TI - Assembly of COPI and COPII Vesicular Coat Proteins on Membranes.
AB - In eukaryotes, distinct transport vesicles functionally connect various
intracellular compartments. These carriers mediate transport of membranes for the
biogenesis and maintenance of organelles, secretion of cargo proteins and
peptides, and uptake of cargo into the cell. Transport vesicles have distinct
protein coats that assemble on a donor membrane where they can select cargo and
curve the membrane to form a bud. A multitude of structural elements of coat
proteins have been solved by X-ray crystallography. More recently, the
architectures of the COPI and COPII coats were elucidated in context with their
membrane by cryo-electron tomography. Here, we describe insights gained from the
structures of these two coat lattices and discuss the resulting functional
implications.
PMID- 29345990
TI - Imaging mRNA In Vivo, from Birth to Death.
AB - RNA is the fundamental information transfer system in the cell. The ability to
follow single messenger RNAs (mRNAs) from transcription to degradation with
fluorescent probes gives quantitative information about how the information is
transferred from DNA to proteins. This review focuses on the latest technological
developments in the field of single-mRNA detection and their usage to study gene
expression in both fixed and live cells. By describing the application of these
imaging tools, we follow the journey of mRNA from transcription to decay in
single cells, with single-molecule resolution. We review current theoretical
models for describing transcription and translation that were generated by single
molecule and single-cell studies. These methods provide a basis to study how
single-molecule interactions generate phenotypes, fundamentally changing our
understating of gene expression regulation.
PMID- 29345991
TI - Collapse Transitions of Proteins and the Interplay Among Backbone, Sidechain, and
Solvent Interactions.
AB - Proteins can collapse into compact globules or form expanded, solvent-accessible,
coil-like conformations. Additionally, they can fold into well-defined three
dimensional structures or remain partially or entirely disordered. Recent
discoveries have shown that the tendency for proteins to collapse or remain
expanded is not intrinsically coupled to their ability to fold. These
observations suggest that proteins do not have to form compact globules in
aqueous solutions. They can be intrinsically disordered, collapsed, or expanded,
and even form well-folded, elongated structures. This ability to decouple
collapse from folding is determined by the sequence details of proteins. In this
review, we highlight insights gleaned from studies over the past decade. Using a
polymer physics framework, we explain how the interplay among sidechains,
backbone units, and solvent determines the driving forces for collapsed versus
expanded states in aqueous solvents. Expected final online publication date for
the Annual Review of Biophysics Volume 47 is May 20, 2018. Please see
http://www.annualreviews.org/page/journal/pubdates for revised estimates.
PMID- 29345992
TI - The Effect of Patient Navigation on the Likelihood of Engagement in Clinical Care
for HIV-Infected Individuals Leaving Jail.
AB - OBJECTIVES: To compare the effectiveness of patient navigation-enhanced case
management in supporting engagement in HIV care upon release from jail relative
to existing services. METHODS: We randomized 270 HIV-infected individuals to
receive navigation-enhanced case management for 12 months or standard case
management for 90 days following release from jail between 2010 and 2013.
Participants were interviewed at 2, 6, and 12 months after release. We abstracted
medical data from jail and city health records. RESULTS: Patient navigation
enhanced case management resulted in greater linkage to care within 30 days of
release (odds ratio [OR] = 2.15; 95% confidence interval [CI] = 1.23, 3.75) and
consistent retention over 12 months (OR = 1.95; 95% CI = 1.11, 3.46). Receipt of
treatment for substance use disorders in jail also resulted in early linkage (OR
= 4.06; 95% CI = 1.93, 8.53) and retention (OR = 2.52; 95% CI = 1.21, 5.23).
Latinos were less likely to be linked to (OR = 0.35; 95% CI = 0.14, 0.91) or
retained in (OR = 0.28; 95% CI = 0.09, 0.82) HIV care. CONCLUSIONS: Patient
navigation supports maintaining engagement in care and can mitigate health
disparities, and should become the standard of care for HIV-infected individuals
leaving jail.
PMID- 29345993
TI - Socioeconomic Outcomes of Women Who Receive and Women Who Are Denied Wanted
Abortions in the United States.
AB - OBJECTIVES: To determine the socioeconomic consequences of receipt versus denial
of abortion. METHODS: Women who presented for abortion just before or after the
gestational age limit of 30 abortion facilities across the United States between
2008 and 2010 were recruited and followed for 5 years via semiannual telephone
interviews. Using mixed effects models, we evaluated socioeconomic outcomes for
813 women by receipt or denial of abortion care. RESULTS: In analyses that
adjusted for the few baseline differences, women denied abortions who gave birth
had higher odds of poverty 6 months after denial (adjusted odds ratio [AOR] =
3.77; P < .001) than did women who received abortions; women denied abortions
were also more likely to be in poverty for 4 years after denial of abortion. Six
months after denial of abortion, women were less likely to be employed full time
(AOR = 0.37; P = .001) and were more likely to receive public assistance (AOR =
6.26; P < .001) than were women who obtained abortions, differences that remained
significant for 4 years. CONCLUSIONS: Women denied an abortion were more likely
than were women who received an abortion to experience economic hardship and
insecurity lasting years. Laws that restrict access to abortion may result in
worsened economic outcomes for women.
PMID- 29345994
TI - Work as an Inclusive Part of Population Health Inequities Research and
Prevention.
AB - Despite its inclusion in models of social and ecological determinants of health,
work has not been explored in most health inequity research in the United States.
Leaving work out of public health inequities research creates a blind spot in our
understanding of how inequities are created and impedes our progress toward
health equity. We first describe why work is vital to our understanding of
observed societal-level health inequities. Next, we outline challenges to
incorporating work in the study of health inequities, including (1) the
complexity of work as a concept; (2) work's overlap with socioeconomic position,
race, ethnicity, and gender; (3) the development of a parallel line of inquiry
into occupational health inequities; and (4) the dearth of precise data with
which to explore the relationships between work and health status. Finally, we
summarize opportunities for advancing health equity and monitoring progress that
could be achieved if researchers and practitioners more robustly include work in
their efforts to understand and address health inequities.
PMID- 29345995
TI - The Effects of Household Medical Expenditures on Income Inequality in the United
States.
AB - OBJECTIVES: To assess the effect of households' outlays for medical expenditures
on income inequality and changes since the implementation of the Affordable Care
Act (ACA). METHODS: We analyzed data from the US Current Population Surveys for
calendar years 2010 through 2014. We calculated the Gini index of income
inequality before and after subtracting households' medical outlays (including
insurance premiums and out-of-pocket costs) from income, the financial burden of
medical outlays for each income decile, and the number of individuals pushed
below poverty by medical outlays. RESULTS: In 2014, the Gini index was 47.84,
which rose to 49.21 after medical outlays were subtracted, indicating that
medical outlays effectively redistributed about 1.37% of total income from poorer
to richer individuals, a slightly smaller redistribution compared with the years
before the ACA. Medical outlays reduced the median income of the poorest decile
by 47.6% versus 2.7% for the wealthiest decile and pushed 7.013 million
individuals into poverty. CONCLUSIONS: The way we finance medical care
exacerbates income inequality and impoverishes millions of Americans. This
regressive financing pattern improved minimally in the wake of the ACA.
PMID- 29345996
TI - Delays in Global Disease Outbreak Responses: Lessons from H1N1, Ebola, and Zika.
AB - In global disease outbreaks, there are significant time delays between the source
of an outbreak and collective action. Some delay is necessary, but recent delays
have been extended by insufficient surveillance capacity and time-consuming
efforts to mobilize action. Three public health emergencies of international
concern (PHEICs)-H1N1, Ebola, and Zika-allow us to identify and compare sources
of delays and consider seven hypotheses about what influences the length of
delays. These hypotheses can then motivate further research that empirically
tests them. The three PHEICs suggest that deferred global mobilization is a
greater source of delay than is poor surveillance capacity. These case study
outbreaks support hypotheses that we see quicker responses for novel diseases
when outbreaks do not coincide with holidays and when US citizens are infected.
They do not support hypotheses that we see quicker responses for more severe
outbreaks or those that threaten larger numbers of people. Better understanding
the reason for delays can help target policy interventions and identify the kind
of global institutional changes needed to reduce the spread and severity of
future PHEICs.
PMID- 29345997
TI - Trends in Health Insurance and Type Among Military Veterans: United States, 2000
2016.
AB - OBJECTIVES: To describe long-term national trends in health insurance coverage
among US veterans from 2000 to 2016 in the context of recent health care reform.
METHODS: We used 2000 to 2016 National Health Interview Survey data on veterans
aged 18 to 64 years to examine trends in insurance coverage and uninsurance by
year, income, and state Medicaid expansion status. We also explored the current
proportions of veterans with each type of insurance by age group. RESULTS: The
percentage of veterans with private insurance decreased from 70.8% in 2000 to
56.9% in 2011, whereas between 2000 and 2016 Department of Veterans Affairs (VA)
health care coverage (only) almost tripled, Medicaid (without concurrent TRICARE
or private coverage) doubled, and TRICARE coverage of any type tripled. After
2011, the percentage of veterans who were uninsured decreased. In 2016, low
income veterans in Medicaid expansion states had double the Medicaid coverage
(41.1%) of low-income veterans in nonexpansion states (20.1%). CONCLUSIONS: Our
estimates, which are nationally representative of noninstitutionalized veterans,
show marked increases in military-related coverage through TRICARE and VA health
care. In 2016, only 7.2% of veterans aged 18 to 64 years and 3.7% of all veterans
(aged 18 years or older) remained uninsured.
PMID- 29345998
TI - Key Factors Inhibiting Legislative Progress Toward Smoke-Free Coverage in
Appalachia.
AB - The Appalachian Region has among the highest rates of smoking and smoking-related
illness in the United States. Strong smoke-free legislation could help protect
nonsmoking residents from the harmful effects of secondhand smoke. However, there
is a dearth of state, county, city, and subcounty smoke-free law coverage
throughout Appalachia. As of July 2016, only 21% of Appalachian residents were
covered by comprehensive smoke-free laws (i.e., 100% coverage for workplaces,
restaurants, and bars). Only 46% of Appalachians lived in places with 100% smoke
free workplace laws, only 30% lived in places with 100% smoke-free restaurant
laws, and only 29% lived in places with 100% smoke-free bar laws. Reasons for
this lack of smoke-free law coverage include socioeconomic disadvantage, the
historical importance of tobacco in Appalachian economies, and preemptive state
legislation. By understanding the contextual issues that have inhibited smoke
free legislation, smoke-free advocates will be better prepared to lead efforts
that expand smoke-free coverage in this region.
PMID- 29345999
TI - Cost-Effectiveness of Capping Freeways for Use as Parks: The New York Cross-Bronx
Expressway Case Study.
AB - OBJECTIVES: To examine health benefits and cost-effectiveness of implementing a
freeway deck park to increase urban green space. METHODS: Using the Cross-Bronx
Expressway in New York City as a case study, we explored the cost-effectiveness
of implementing deck parks. We built a microsimulation model that included
increased exercise, fewer accidents, and less pollution as well as the cost of
implementation and maintenance of the park. We estimated both the quality
adjusted life years gained and the societal costs for 2017. RESULTS:
Implementation of a deck park over sunken parts of Cross-Bronx Expressway
appeared to save both lives and money. Savings were realized for 84% of Monte
Carlo simulations. CONCLUSIONS: In a rapidly urbanizing world, reclaiming green
space through deck parks can bring health benefits alongside economic savings
over the long term. Public Health Implications. Policymakers are seeking ways to
create cross-sectorial synergies that might improve both quality of urban life
and health. However, such projects are very expensive, and there is little
information on their return of investment. Our analysis showed that deck parks
produce exceptional value when implemented over below-grade sections of road.
PMID- 29346000
TI - Preventable Emergency Department Visits for Nontraumatic Dental Conditions:
Trends and Disparities in Nevada, 2009-2015.
AB - OBJECTIVES: To examine trends and socioeconomic disparities for preventable
dental-related emergency department (ED) visits in Nevada. METHODS: We pooled
retrospective data containing 66 267 ED visits involving dental conditions from
Nevada hospital ED databases from 2009 to 2015. The dependent variable was
nontraumatic dental conditions identified by International Classification of
Diseases, Ninth Revision, codes; 3 independent variables included treatment year,
health insurance status, and race/ethnicity. RESULTS: Odds of ED visits for
nontraumatic dental conditions increased 16% annually from 2009 to 2015 (odds
ratio [OR] = 1.16; 95% confidence interval [CI] = 1.13, 1.19). Medicaid (OR =
2.16; 95% CI = 1.96, 2.39) and uninsured patients (OR = 2.75; 95% CI = 2.52,
3.00) presenting with nontraumatic dental conditions were 1 to 2 times more
likely than those with private dental insurance to seek ED treatment. Black
patients were more likely than White patients to seek ED treatment (OR = 1.13;
95% CI = 1.02, 1.24). CONCLUSIONS: Socioeconomic and demographic factors were
significantly associated with ED visits for nontraumatic dental conditions, with
a steady increase in trends and a widening of socioeconomic disparities in recent
years.
PMID- 29346001
TI - Strategies and Challenges in Preventing Violence Against Canadian Indoor Sex
Workers.
AB - OBJECTIVES: To examine indoor sex workers' strategies in preventing workplace
violence and influential socio-structural conditions. METHODS: Data included
qualitative interviews with 85 sex workers in British Columbia, Canada, from 2014
through 2016. For analyses, we used interpretive thematic techniques informed by
World Health Organization position statements on violence. RESULTS: Robbery,
nonpayment, financial exploitation, and privacy violations were frequent types of
violence perpetrated by clients, landlords, and neighbors. We identified 2 themes
that depicted how sex workers prevented violence and mitigated its effects: (1)
navigating physical spaces and (2) navigating client relationships. CONCLUSIONS:
Sex workers' diverse strategies to prevent violence and mitigate its effects are
creative and effective in many circumstances. These are limited, however, by the
absence of legal and public health regulations governing occupational health and
safety and stigma associated with sex work. Public Health Implications.
Occupational health and safety regulatory policies that set conditions for
clients' substance and condom use within commercial sex transactions are
required. Revisions to the current legal regulations governing prostitution are
critical to support optimal work environments that reduce the likelihood of
violence. These revisions must recognize sex work as a form of labor versus
victimization.
PMID- 29346003
TI - Medicaid Expansion and Infant Mortality in the United States.
AB - OBJECTIVES: To explore the effect of Medicaid expansion on US infant mortality
rate. METHODS: We examined data from 2010 to 2016 and 2014 to 2016 to compare
infant mortality rates in states and Washington, DC, that accepted the Affordable
Care Act Medicaid expansion (Medicaid expansion states) and states that did not
(non-Medicaid expansion states), stratifying data by race/ethnicity. RESULTS:
Mean infant mortality rate in non-Medicaid expansion states rose (6.4 to 6.5)
from 2014 to 2016 but declined in Medicaid expansion states (5.9 to 5.6). Mean
difference in infant mortality rate in Medicaid expansion versus non-Medicaid
expansion states increased from 0.573 (P = .08) in 2014 to 0.838 in 2016 (P =
.006) because of smaller declines in non-Medicaid expansion (11.0%) than in
Medicaid expansion (15.2%) states. The 14.5% infant mortality rate decline from
11.7 to 10.0 in African American infants in Medicaid expansion states was more
than twice that in non-Medicaid expansion states (6.6%: 12.2 to 11.4; P = .012).
CONCLUSIONS: Infant mortality rate decline was greater in Medicaid expansion
states, with greater declines among African American infants. Future research
should explore what aspects of Medicaid expansion may improve infant survival.
PMID- 29346002
TI - Intermittent Preventive Therapy in Pregnancy and Incidence of Low Birth Weight in
Malaria-Endemic Countries.
AB - OBJECTIVES: To estimate the impact of hypothetical antimalarial and nutritional
interventions (which reduce the prevalence of low midupper arm circumference
[MUAC]) on the incidence of low birth weight (LBW). METHODS: We analyzed data
from 14 633 pregnancies from 13 studies conducted across Africa and the Western
Pacific from 1996 to 2015. We calculated population intervention effects for
increasing intermittent preventive therapy in pregnancy (IPTp), full coverage
with bed nets, reduction in malaria infection at delivery, and reductions in the
prevalence of low MUAC. RESULTS: We estimated that, compared with observed IPTp
use, administering 3 or more doses of IPTp to all women would decrease the
incidence of LBW from 9.9% to 6.9% (risk difference = 3.0%; 95% confidence
interval = 1.7%, 4.0%). The intervention effects for eliminating malaria at
delivery, increasing bed net ownership, and decreasing low MUAC prevalence were
all modest. CONCLUSIONS: Increasing IPTp uptake to at least 3 doses could
decrease the incidence of LBW in malaria-endemic countries. The impact of IPTp on
LBW was greater than the effect of prevention of malaria, consistent with a
nonmalarial effect of IPTp, measurement error, or selection bias.
PMID- 29346004
TI - Universal Lead Screening Requirement: A California Case Study.
AB - OBJECTIVES: To estimate potential impacts of California Assembly Bill (AB) 1316:
a requirement for universal screening and insurance coverage for child blood lead
testing. METHODS: In April 2017 the California Health Benefits Review Program
(Oakland, CA) analyzed AB 1316 for the California legislature, including a
systematic review of lead screening effectiveness, commercial insurer surveys
regarding screening coverage, and actuarial utilization and cost implication
assessments. RESULTS: Universal screening requirements would increase child lead
testing by 273%, raise affected populations' premiums by 0.0043%, and detect an
additional 4777 exposed children 1 year after implementation. CONCLUSIONS: The
evidence for a net societal benefit of universal screening approach is limited
and is not supported by prominent medical professional groups. Public Health
Implications. California expanded targeted screening to identify additional
children at higher risk for lead poisoning on the basis of California-specific
risk factors, while mitigating the potential harms of universal screening such as
an increase in false positive tests and health care costs.
PMID- 29346005
TI - Ethical Issues in Social Media Research for Public Health.
AB - Social media (SM) offer huge potential for public health research, serving as a
vehicle for surveillance, delivery of health interventions, recruitment to
trials, collection of data, and dissemination. However, the networked nature of
the data means they are riddled with ethical challenges, and no clear consensus
has emerged as to the ethical handling of such data. This article outlines the
key ethical concerns for public health researchers using SM and discusses how
these concerns might best be addressed. Key issues discussed include privacy;
anonymity and confidentiality; authenticity; the rapidly changing SM environment;
informed consent; recruitment, voluntary participation, and sampling; minimizing
harm; and data security and management. Despite the obvious need, producing a set
of prescriptive guidelines for researchers using SM is difficult because the
field is evolving quickly. What is clear, however, is that the ethical issues
connected to SM-related public health research are also growing. Most
importantly, public health researchers must work within the ethical principles
set out by the Declaration of Helsinki that protect individual users first and
foremost.
PMID- 29346006
TI - Public Health Education: Teaching Epidemiology in High School Classrooms.
AB - Epidemiology instruction has expanded at the undergraduate level in part because
it increases student critical thinking and scientific literacy, promotes
students' perception of public health as both practical and relevant, and
empowers students as independent, lifelong learners. Why then are more high
schools not adopting epidemiology as a course requirement for students? Although
prior iterations of high school epidemiology courses are noteworthy for
incorporating active and participatory learning, embedding them into existing and
continually shifting curricula is challenging and time-consuming, especially for
teachers not trained in the field. It also may be argued that currently available
epidemiology teaching resources emphasize content rather than thinking skills and
therefore do not optimally promote students' personal engagement with, and in
depth understanding of, the mission and goals of public health. I propose a new
framework for high school epidemiology that draws from progressive education
ideology, including three critical elements: empowerment, authenticity, and
transfer. I provide multiple examples to show how this framework has been used
across a wide array of settings to hone epidemiology thinking skills in high
school students.
PMID- 29346007
TI - The Rise and Fall of "Universal Health Coverage" as a Goal of International
Health Politics, 1925-1952.
AB - The UN Sustainable Development Goals of 2015 have restored universal health
coverage (UHC) to prominence in the international health agenda. Can
understanding the past illuminate the prospects for UHC in the present? This
article traces an earlier history of UHC as an objective of international health
politics. Its focus is the efforts of the International Labor Organization (ILO),
whose Philadelphia Declaration (1944) announced the goal of universal social
security, including medical coverage and care. After World War II, the ILO
attempted to enshrine this in an international convention, which nation states
would ratify. However, by 1952 these efforts had failed, and the final convention
was so diluted that universalism was unobtainable. Our analysis first explains
the consolidation of ideas about social security and health care, tracing
transnational policy linkages among experts whose world view transcended narrow
loyalties. We then show how UHC goals became marginalized, through the opposition
of employers and organized medicine, and of certain nation states, both rich and
poor. We conclude with reflections on how these findings might help us in
thinking about the challenges of advancing UHC today.
PMID- 29346008
TI - Follow-Up Care Provider Preferences of Adolescent and Young Adult Cancer
Survivors.
AB - PURPOSE: To explore the experiences and perspectives of adolescent and young
adult (AYA) cancer survivors regarding patient-provider relationships and their
preferences surrounding type of healthcare provider for follow-up care. METHODS:
We recruited AYA cancer survivors who were diagnosed between the ages of 15 and
39 using the Utah Cancer Registry. Twenty-eight survivors participated in six
focus groups held between March and May of 2015 in Salt Lake City and St. George,
Utah. This analysis focuses on how survivors' preferences about type of
healthcare provider may influence their transition into, and utilization of,
follow-up care. RESULTS: On average, survivors were 6.3 (standard deviation =
1.7) years from their cancer diagnosis. A majority of survivors expressed a
desire not to transition to a new provider and preferred continuing to see their
oncologist for follow-up care. For these survivors, this was due to already
having a close relationship with their oncologist and because they trusted their
provider's knowledge about cancer and how to handle late effects. However,
survivors placed emphasis on being comfortable with their healthcare provider,
regardless of provider type. CONCLUSIONS: Our findings demonstrate the importance
of formalizing provider transitions and roles after cancer therapy to improve
patient comfort with new providers. By understanding the complexities of the
transition from active cancer treatment to follow-up care for AYA survivors,
these findings can inform programs undertaking post-care educational activities
to ensure a seamless transition into survivorship care. Survivorship care plans
can facilitate these transitions and improve patient confidence in follow-up
care.
PMID- 29346009
TI - Automation on an Open-Access Platform of Alzheimer's Disease Biomarker
Immunoassays.
AB - The lack of (inter-)laboratory standardization has hampered the application of
universal cutoff values for Alzheimer's disease (AD) cerebrospinal fluid (CSF)
biomarkers and their transfer to general clinical practice. The automation of the
AD biomarker immunoassays is suggested to generate more robust results than using
manual testing. Open-access platforms will facilitate the integration of
automation for novel biomarkers, allowing the introduction of the protein
profiling concept. A feasibility study was performed on an automated open-access
platform of the commercial immunoassays for the 42-amino-acid isoform of amyloid
beta (Abeta1-42), Abeta1-40, and total tau in CSF. Automated Abeta1-42, Abeta1
40, and tau immunoassays were performed within predefined acceptance criteria for
bias and imprecision. Similar accuracy was obtained for ready-to-use calibrators
as for reconstituted lyophilized kit calibrators. When compared with the addition
of a standard curve in each test run, the use of a master calibrator curve,
determined before and applied to each batch analysis as the standard curve,
yielded an acceptable overall bias of -2.6% and -0.9% for Abeta1-42 and Abeta1
40, respectively, with an imprecision profile of 6.2% and 8.4%, respectively. Our
findings show that transfer of commercial manual immunoassays to fully automated
open-access platforms is feasible, as it performs according to universal
acceptance criteria.
PMID- 29346010
TI - Identification and Correction of Additive and Multiplicative Spatial Biases in
Experimental High-Throughput Screening.
AB - Data generated by high-throughput screening (HTS) technologies are prone to
spatial bias. Traditionally, bias correction methods used in HTS assume either a
simple additive or, more recently, a simple multiplicative spatial bias model.
These models do not, however, always provide an accurate correction of
measurements in wells located at the intersection of rows and columns affected by
spatial bias. The measurements in these wells depend on the nature of interaction
between the involved biases. Here, we propose two novel additive and two novel
multiplicative spatial bias models accounting for different types of bias
interactions. We describe a statistical procedure that allows for detecting and
removing different types of additive and multiplicative spatial biases from
multiwell plates. We show how this procedure can be applied by analyzing data
generated by the four HTS technologies (homogeneous, microorganism, cell-based,
and gene expression HTS), the three high-content screening (HCS) technologies
(area, intensity, and cell-count HCS), and the only small-molecule microarray
technology available in the ChemBank small-molecule screening database. The
proposed methods are included in the AssayCorrector program, implemented in R,
and available on CRAN.
PMID- 29346011
TI - Minimally Invasive Management of Severe Aortoiliac Occlusive Disease.
AB - BACKGROUND: Peripheral arterial disease (PAD) is a complex and highly prevalent
pathology. It has been estimated that ~8.5 million people in the United States
are affected by PAD, of which 12%-20% are older than age 60. The TransAtlantic
Inter-Society Consensus (TASC) guidelines classified aortoiliac atherosclerotic
disease based on morphology and level of lesions. TASC II guidelines recommend
bilateral surgical bypass to the femoral arteries for TASC II C and D lesions.
The aortobifemoral bypass (ABF) has been considered the gold standard in the
treatment of aortoiliac occlusive disease (AIOD). The long-term patency rate of
85%-90% at 5 years and 75%-80% at 10 years has been for a long time unmatched by
other methods of revascularization. METHODS: This is a review of the current
literature regarding minimally invasive strategies in the care of TASC II C and D
aortoiliac disease. RESULTS: Endovascular therapies have led to a paradigm change
even in the treatment of highly advanced lesions. Reconstruction of the aortic
bifurcation for distal aortic and/or ostial unilateral/bilateral common iliac
artery disease can be achieved via the deployment of stents with "kissing"
technique and aortic endografts. Laparoscopic aortoiliac surgery for TASC II C
and D lesions was first proposed in 1993. Total laparoscopic, laparoscopic
assisted, and laparobotic techniques have been described. Minimal incision aortic
surgery (MIAS) describes abdominal incisions varying from 6 to 12 cm and
positional adjustment of retractors to access the retroperitoneum for infrarenal
aortic aneurysms and/or AIOD. CONCLUSIONS: Although initial enthusiasm
laparoscopic aortic surgery and MIAS have failed to gain acceptance in the
vascular surgery community due to intrinsic procedural challenges, they are
currently practiced in few highly specialized centers. At this moment, high
quality evidence is lacking regarding the further feasibility of these techniques
and their applicability in general practice compared to endovascular therapies.
While the ABF remains still the optimal choice in select, fit for surgery
patients, endovascular therapies offer a less invasive approach that may provide
a mortality and morbidity benefit in higher risk patients with acceptable short-
and long-term outcomes.
PMID- 29346012
TI - The Combination of Probiotic Complex, Rosavin, and Zinc Improves Pain and
Cartilage Destruction in an Osteoarthritis Rat Model.
AB - Osteoarthritis (OA), a degenerative disorder, induces pain, joint inflammation,
and destruction of the articular cartilage matrix. Probiotic complex, rosavin,
and zinc have been used as dietary supplements that exhibit anti-inflammatory and
antioxidant properties. However, there is no evidence demonstrating a synergic
effect in OA. This study aims to determine whether combination with probiotic
complex, rosavin, and zinc decreases progression of monosodium iodoacetate (MIA)
induced OA rat model. The combination improved pain levels by preventing
cartilage damage. The expression of proinflammatory cytokines and catabolic
factors was reduced by the combination within the joint tissue. However, the
combination increased anti-inflammatory cytokines as well as the anabolic factor
production. The gene level of catabolic factors was decreased with treatment of
the combination in chondrocytes isolated from OA patients. These results suggest
that the combination can improve MIA development through the inhibition of
proinflammatory cytokines and cartilage destruction, thus playing a key role as a
therapeutic candidate for OA treatment.
PMID- 29346013
TI - Purification of Lymphocytes by Acoustic Separation in Plastic Microchannels.
AB - Emerging cell therapies have created new demands for instruments that will
increase processing efficiency. Purification of lymphocytes prior to downstream
steps of gene transfer currently relies on centrifugal separation, which has
drawbacks in output sample purity and process automation. Here, we present an
alternative approach to blood cell purification using acoustic forces in plastic
microchannels. We provide details regarding the system's ability to purify
lymphocytes relative to other blood cell types while maintaining a high overall
recovery, testing performance starting from leukapheresis product, buffy coat,
and whole blood. Depending on settings, the device achieves for lymphocytes up to
97% purity and up to 68% recovery, and depletes 98% of monocytes while also
reducing red cells and platelets. We expect that future scale-up of our system
for increased throughput will enable its incorporation in the cell therapy
workflow, and that it could ultimately reduce costs and expand access for
patients.
PMID- 29346014
TI - Role of the Lymphatic System in the Pathogenesis of Hypertension in Humans.
AB - BACKGROUND: Recent studies, mainly on animal models, have suggested that
negatively charged glycosaminoglycans, macrophages, and lymph vessels in the skin
interstitium may serve as extrarenal control of sodium balance and blood
pressure. The aim of the study was to prove the hypothesis that skin interstitium
has a role in the pathogenesis of hypertension in humans. METHODS AND RESULTS: We
have examined skin biopsies in 91 patients from the department of surgery who had
elective surgery with abdominal skin incision: 43 were hypertensive, 14 had
resistant hypertension, and 34 with normal blood pressure as control group
(median patients' age in these groups estimated accordingly 64 vs. 64 vs. 61.5; p
> 0.05). We have studied (1) the content of Na+, water, accumulation of
macrophages (CD68), and density of lymphatic vessels (D2-40) and blood vessels
(CD31) in the specimens of abdominal skin taken at the time of surgery and (2)
plasma NT-proANP, vascular endothelial growth factor (VEGF)-C, and VEGF-D
concentrations. The study groups differed in skin expression of CD68 (control vs.
hypertension vs. resistant hypertension groups were accordingly: 3.33 vs. 4.00
vs. 8.33; p = 0.005) and in serum concentration of VEGF-C (5792 vs. 4348 vs. 3974
pg/mL; p = 0.026). Differences among groups in plasma NT-proANP levels were close
to statistical significance (p = 0.056). CONCLUSIONS: Our results confirm that
skin interstitium may be involved in the pathogenesis of essential hypertension
in humans. Lower levels of VEGF-C in hypertensive groups suggest that impairment
of lymphangiogenesis and protective function of the skin lymphatic system may
play a role in the pathogenesis of hypertension.
PMID- 29346015
TI - Treatment of a textile effluent by adsorption with cork granules and titanium
dioxide nanomaterial.
AB - This study aimed to explore the efficiency of two adsorbents, cork granules with
different granulometry and titanium dioxide nanomaterial, in the removal of
chemical oxygen demand (COD), colour and toxicity from a textile effluent. The
adsorption assays with cork were unsatisfactory in the removal of chemical
parameters however they eliminated the acute toxicity of the raw effluent to
Daphnia magna. The assay with TiO2 NM did not prove to be efficient in the
removal of colour and COD even after 240 min of contact; nevertheless it also
reduced the raw effluent toxicity. The best approach for complete remediation of
the textile effluent has not yet been found however promising findings were
achieved, which may be an asset in future adsorption assays.
PMID- 29346016
TI - In situ electrochemical manipulation of oxidation-reduction potential in
saturated subsurface matrices.
AB - Application of a low-intensity electric field is known to influence oxidation
reduction (redox) potential in a saturated matrix. In this study, such redox
manipulation was attempted in at a site with contaminated aquifer. At the
experiment field site, electrodes connected to a direct current (DC) source
provided an electric field with an intensity of 1.82 V m-1. Redox potentials at
locations 3.0 m and 7.9 m from the cathode decreased by 111 mV and 33 mV within a
few hours, respectively, indicating that reducing conditions in the aquifer may
be established within the electric field. Overall, it is possible to manipulate
in situ redox potential in saturated subsurface matrices by applying low
intensity electric fields.
PMID- 29346017
TI - The Role of Posterior Parietal Cortex in Beat-based Timing Perception: A
Continuous Theta Burst Stimulation Study.
AB - There is growing interest in how the brain's motor systems contribute to the
perception of musical rhythms. The Action Simulation for Auditory Prediction
hypothesis proposes that the dorsal auditory stream is involved in bidirectional
interchange between auditory perception and beat-based prediction in motor
planning structures via parietal cortex [Patel, A. D., & Iversen, J. R. The
evolutionary neuroscience of musical beat perception: The Action Simulation for
Auditory Prediction (ASAP) hypothesis. Frontiers in Systems Neuroscience, 8, 57,
2014]. We used a TMS protocol, continuous theta burst stimulation (cTBS), that is
known to down-regulate cortical activity for up to 60 min following stimulation
to test for causal contributions to beat-based timing perception. cTBS target
areas included the left posterior parietal cortex (lPPC), which is part of the
dorsal auditory stream, and the left SMA (lSMA). We hypothesized that down
regulating lPPC would interfere with accurate beat-based perception by disrupting
the dorsal auditory stream. We hypothesized that we would induce no interference
to absolute timing ability. We predicted that down-regulating lSMA, which is not
part of the dorsal auditory stream but has been implicated in internally timed
movements, would also interfere with accurate beat-based timing perception. We
show ( n = 25) that cTBS down-regulation of lPPC does interfere with beat-based
timing ability, but only the ability to detect shifts in beat phase, not changes
in tempo. Down-regulation of lSMA, in contrast, did not interfere with beat-based
timing. As expected, absolute interval timing ability was not impacted by the
down-regulation of lPPC or lSMA. These results support that the dorsal auditory
stream plays an essential role in accurate phase perception in beat-based timing.
We find no evidence of an essential role of parietal cortex or SMA in interval
timing.
PMID- 29346018
TI - The Tortoise and the Hare: Interactions between Reinforcement Learning and
Working Memory.
AB - Learning to make rewarding choices in response to stimuli depends on a slow but
steady process, reinforcement learning, and a fast and flexible, but capacity
limited process, working memory. Using both systems in parallel, with their
contributions weighted based on performance, should allow us to leverage the best
of each system: rapid early learning, supplemented by long-term robust
acquisition. However, this assumes that using one process does not interfere with
the other. We use computational modeling to investigate the interactions between
the two processes in a behavioral experiment and show that working memory
interferes with reinforcement learning. Previous research showed that neural
representations of reward prediction errors, a key marker of reinforcement
learning, were blunted when working memory was used for learning. We thus
predicted that arbitrating in favor of working memory to learn faster in simple
problems would weaken the reinforcement learning process. We tested this by
measuring performance in a delayed testing phase where the use of working memory
was impossible, and thus participant choices depended on reinforcement learning.
Counterintuitively, but confirming our predictions, we observed that associations
learned most easily were retained worse than associations learned slower: Using
working memory to learn quickly came at the cost of long-term retention.
Computational modeling confirmed that this could only be accounted for by working
memory interference in reinforcement learning computations. These results further
our understanding of how multiple systems contribute in parallel to human
learning and may have important applications for education and computational
psychiatry.
PMID- 29346019
TI - Independent Attention Mechanisms Control the Activation of Tactile and Visual
Working Memory Representations.
AB - Working memory (WM) is limited in capacity, but it is controversial whether these
capacity limitations are domain-general or are generated independently within
separate modality-specific memory systems. These alternative accounts were tested
in bimodal visual/tactile WM tasks. In Experiment 1, participants memorized the
locations of simultaneously presented task-relevant visual and tactile stimuli.
Visual and tactile WM load was manipulated independently (one, two, or three
items per modality), and one modality was unpredictably tested after each trial.
To track the activation of visual and tactile WM representations during the
retention interval, the visual contralateral delay activity (CDA) and tactile CDA
(tCDA) were measured over visual and somatosensory cortex, respectively. CDA and
tCDA amplitudes were selectively affected by WM load in the corresponding
(tactile or visual) modality. The CDA parametrically increased when visual load
increased from one to two and to three items. The tCDA was enhanced when tactile
load increased from one to two items and showed no further enhancement for three
tactile items. Critically, these load effects were strictly modality-specific, as
substantiated by Bayesian statistics. Increasing tactile load did not affect the
visual CDA, and increasing visual load did not modulate the tCDA. Task
performance at memory test was also unaffected by WM load in the other (untested)
modality. This was confirmed in a second behavioral experiment where tactile and
visual loads were either two or four items, unimodal baseline conditions were
included, and participants performed a color change detection task in the visual
modality. These results show that WM capacity is not limited by a domain-general
mechanism that operates across sensory modalities. They suggest instead that WM
storage is mediated by distributed modality-specific control mechanisms that are
activated independently and in parallel during multisensory WM.
PMID- 29346020
TI - Sequential Ridge Augmentation Protocol for Hard and Soft Tissue Grafting in
Alveolar Ridge Deficiencies: A Proposed Evidence-Based Algorithm.
PMID- 29346021
TI - Extending Implications of Study Findings on Real-World Implementation.
PMID- 29346022
TI - The Road From Theory to Reality: Illuminating the Complexity of Prospective
Cancer Bundles.
PMID- 29346023
TI - Fertility Preservation in Pediatric Oncology Patients: New Perspectives.
AB - Over the past 30 years, advances in antineoplastic treatment led to a significant
increase in the survival of patients with childhood cancer. In Europe and the
United States, 82% of children, adolescents, and young adults survive 5 years
from the cancer diagnosis and the majority achieves long-term survival into
adulthood. The impact of cancer therapy on fertility is related to the age of the
patient and to the duration, dose/intensity, and type of treatment. Exposure to
chemotherapy or to radiation to gonads or pituitary brings long-term
complications of cancer-directed therapies that include effects on reproductive
capacity. Different methods to preserve fertility can be offered. In prepubertal
women, ovarian tissue freezing, in vitro maturation, and surgical movement of
ovaries outside the field of irradiation are still experimental. In pubertal and
postpubertal women, oocyte-embryo freezing is an established option. In men, the
options are sperm cryopreservation, gonadal transposition, and testicular tissue
or spermatogonial cryopreservation and reimplantation. Fertility risks and
provision of strategies to minimize cancer treatment impact fertility include
discussion of the tail of the option before cancer treatment. Having to make a
decision in a limited time, while still coming to terms with a potentially life
threatening diagnosis, can cause patients to feel overwhelmed. To date, there are
no uniform guidelines on how to approach this problem, so it is important to be
aware of it for proper clinical practice.
PMID- 29346024
TI - Occurrence of polycyclic aromatic hydrocarbons in surface water and hospital
wastewater.
AB - The main objective of this study was to determine the occurrence of polycyclic
aromatic hydrocarbons (PAHs) in surface water samples collected from different
points along the stream that flows through the Campus of the Federal University
of Santa Maria, RS-Brazil. Before reaching the campus, the water in the stream is
already contaminated by wastewater discharged from the surrounding, and once
inside the Campus, additional wastewater from a Gas Station situated close to the
University hospital. A bench scale photodegradation experiment was conducted of
the occurring traces of anthracene, phenanthrene and naphthalene, with the aid of
a stirred tank reactor and polymer-supported TiO2 as a catalyst. To prevent loss
of the low soluble analytes, it was necessary to add 5% and 10% acetonitrile, as
an organic modifier of the synthetic aqueous solutions and real samples,
respectively. An experimental design was employed and the best conditions for the
photocatalysis of the aqueous solutions and real samples were pH 9 and pH 7, and
35 degrees C and 30 degrees C, respectively. Under optimized conditions, the
analytes were completely degraded after 60 min of irradiation. The subproducts of
the photocatalysis were identified through gas chromatography/mass spectrometry,
and fragmentation routes were proposed. The mean concentrations of PAHs in the
polluted surface water and hospital wastewater were relatively high: 3.9 +/- 1.7
and 21.5 +/- 2.8 ug L-1, respectively. A preliminary risk assessment revealed
that the presence of anthracene requires particular attention. The risk posed by
the occurrence of PAHs in the surface water and hospital wastewater samples
confirms the need for an efficient treatment system.
PMID- 29346025
TI - Linkage of Metabolic Defects to Activated PIK3CA Alleles in Endothelial Cells
Derived from Lymphatic Malformation.
AB - BACKGROUND: Lymphatic endothelial cells (LECs) derived from lymphatic
malformations (LMs) bear activated PIK3CA alleles yet display an inflammatory
gene expression profile. A basis for the inflammatory phenotype was sought by
screening for coexisting somatic mutations. METHODS AND RESULTS: Fourteen
independent LEC populations bearing activated PIK3CA alleles were isolated from
LM. These were characterized by the expression of growth and inflammatory genes
(VEGFC, IL-6, COX-2, IL-8, HO-1, E-SEL) by qRT-PCR. Most commonly upregulated
gene products were VEGFC, COX2, HO-1, and ANGPTL4. The specific inhibition of
PI3K reduced VEGFC expression without resolving inflammation. Whole exome
sequencing of six LM-LEC populations identified five novel somatically acquired
alleles coexisting with activated PIK3CA alleles. Two affected genes regulate
lipid droplet metabolism (FITM2 and ATG2A), two are gene regulators (MTA1 and
TAF1L), and the fifth is an isoform of ANK3 (an endosomal/lysosomal protein).
Inhibition of AMPK implicated its involvement in regulating COX-2 and HO-1
overexpression. ANGPTL4 expression was independent of AMPK and PI3K activity and
reflected lipid stress demonstrated in normal LECs. AMPK activation with AICAR
had a selective growth-limiting effect in a subset of LM-LEC isolates.
CONCLUSIONS: Inflammatory stress displayed by LM-LECs is consistent with errors
in lipid metabolism that may be linked to acquired mutations. The acquisition of
PIK3CA alleles may be a permissive event that antagonizes inflammation and
metabolic defect.
PMID- 29346026
TI - A Scintigraphic Method for Quantitation of Lymphatic Function in Arm Lymphedema.
AB - BACKGROUND: Lymphoscintigraphy is commonly used to assess breast cancer-related
lymphedema. However, a reliable quantitative method that clearly distinguishes
normal lymphatic function from lymphedema is desired. We propose a quantitative
method based upon the physiological mean transit time (MTT) measure of lymph
fluid passing through the arm. METHODS AND RESULTS: Eleven patients, aged 34-68
years, with unilateral arm lymphedema following breast cancer treatment underwent
simultaneous bilateral lymphoscintigraphy using intradermal injection of 99mTc
labeled human serum albumin (HSA). Imaging was performed at 30-45 minute
intervals for 5 hours. Time activity curves from each injection site and each arm
region were recorded. The input into the arm region was obtained as the (minus)
time derivative of the injection site activity curve. In the proposed model the
arm activity curve was considered to arise from the convolution of the retention
function and the input function. The retention function was obtained by fitting
the calculated arm activity curve to the measured arm activity curve. The MTT of
activity passing through the arm was calculated as the time integral of the
resulting retention function. All measured time activity curves were well
described by the model. The MTT of the lymphedema arm (mean 60.1 minutes, range
22-105 minutes) was markedly different from that of the contralateral normal arm
(mean 5.4 minutes, range 1.2-8.7 minutes), p < 0.0001. CONCLUSION: The proposed
model showed great similarity with measured time activity curves and was capable
of quantitatively distinguishing lymphatic function of the lymphedema arm from
that of the normal arm in terms of calculated MTT.
PMID- 29346027
TI - Postsurgical Outcomes and Surgical Completeness of Robotic Thyroid Surgery: A
Single Surgeon's Experience on 700 Cases.
AB - BACKGROUND: Advanced technology and understanding of robotic surgical system have
rendered robotic thyroid surgery more expanding. The aim of this study was to
identify the periodic changes in postsurgical outcomes of robotic thyroid surgery
performed by a single surgeon. METHODS: We conducted a retrospective review of
700 robotic thyroid surgery cases using gasless trans-axillary approach. RESULTS:
All patients underwent successful operations without conversion to open surgery,
and were mostly younger than 45 years, female, less-extended thyroid surgery and
lymph node dissection, and thyroid cancer. The median follow-up period was 67
months (12-99 months). Regarding technical outcomes, the operation time declined
steeply after 100 consecutive cases, and reached 120.0-132.7 minutes for thyroid
lobectomy and 162.9-174.1 minutes for total thyroidectomy (TT). The most common
complication was transient hypoparathyroidism (43.7%), whose incidence decreased
steeply to a range of 9.1% to 25.0% after 300 consecutive cases. Regarding
surgical completeness for thyroid cancer, an average of seven lymph nodes was
retrieved through central compartment node dissection without fluctuation over
time. The proportion of the patients with serum stimulated thyroglobulin levels
<10 ng/mL at the time of radioactive iodine remnant ablation after TT and <1
ng/mL 6-12 months after the first remnant ablation ranged between 86.4%-100% and
66.7%-100%, respectively, without significant fluctuation. CONCLUSION: For
properly selected patients, robotic thyroid surgery is useful surgical option
with reliable technical outcome and surgical completeness and cosmetic benefit.
PMID- 29346029
TI - Unifying Visual Space Across the Left and Right Hemifields.
AB - Visual space is perceived as continuous and stable even though visual inputs from
the left and right visual fields are initially processed separately within the
two cortical hemispheres. In the research reported here, we examined whether the
visual system utilizes a dynamic recalibration mechanism to integrate these
representations and to maintain alignment across the visual fields. Subjects
adapted to randomly oriented moving lines that straddled the vertical meridian;
these lines were vertically offset between the left and right hemifields.
Subsequent vernier alignment judgments revealed a negative aftereffect: An offset
in the same direction as the adaptation was required to correct the perceived
misalignment. This aftereffect was specific to adaptation to vertical, but not
horizontal, misalignments and also occurred following adaptation to movie clips
and patterns without coherent motion. Our results demonstrate that the visual
system unifies the left and right halves of visual space by continuously
recalibrating the alignment of elements across the visual fields.
PMID- 29346030
TI - The Challenge of Surgical Sepsis.
PMID- 29346031
TI - 2016 New Horizons Lecture: Beyond Imaging-Radiology of Tomorrow.
AB - This article is based on the New Horizons lecture delivered at the 2016
Radiological Society of North America Annual Meeting. It addresses looming
changes for radiology, many of which stem from the disruptive effects of the
Fourth Industrial Revolution. This is an emerging era of unprecedented rapid
innovation marked by the integration of diverse disciplines and technologies,
including data science, machine learning, and artificial intelligence
technologies that narrow the gap between man and machine. Technologic advances
and the convergence of life sciences, physical sciences, and bioengineering are
creating extraordinary opportunities in diagnostic radiology, image-guided
therapy, targeted radionuclide therapy, and radiology informatics, including
radiologic image analysis. This article uses the example of oncology to make the
case that, if members in the field of radiology continue to be innovative and
continuously reinvent themselves, radiology can play an ever-increasing role in
both precision medicine and value-driven health care. (c) RSNA, 2018.
PMID- 29346032
TI - Pathways Into Literacy: The Role of Early Oral Language Abilities and Family Risk
for Dyslexia.
AB - The present study investigated the role of early oral language and family risk
for dyslexia in the two developmental pathways toward reading comprehension,
through word reading and through oral language abilities. The sample contained
237 children (164 at family risk for dyslexia) from the Dutch Dyslexia Program.
Longitudinal data were obtained on seven occasions when children were between 4
and 12 years old. The relationship between early oral language ability and
reading comprehension at the age of 12 years was mediated by preliteracy skills
and word-decoding ability for the first pathway and by later language abilities
for the second pathway. Family risk influenced literacy development through its
subsequent relations with preliteracy skills, word decoding, and reading
comprehension. Although performance on language measures was often lower for the
family-risk group than for the no-family-risk group, family risk did not have a
specific relation with either early or later oral language abilities.
PMID- 29346033
TI - The psychology of elite cycling: a systematic review.
AB - This systematic review sought to synthesise what is currently known about the
psychology of elite cycling. Nine electronic databases were searched in March
2017 for studies reporting an empirical test of any psychological construct in an
elite cycling sample. Fourteen studies (total n = 427) met inclusion criteria.
Eight studies were coded as having high risk of bias. Themes extracted included
mood, anxiety, self-confidence, pain, and cognitive function. Few studies had
similar objectives meaning that in many instances findings could not be
synthesised in a meaningful way. Nevertheless, there was some cross-study
evidence that elite cyclists have more positive mood states (relative to
normative scores), pre-race anxiety impairs performance (among male cyclists),
and associative strategies are perceived as helpful for pain management. Among
single studies coded as having low risk of bias, evidence suggests that implicit
beliefs affect decision making performance, elite cyclists are less susceptible
to mental fatigue (than non-elite cyclists), and better leadership skills relates
to greater social labouring. Limitations include non-standardisation of measures,
lack of follow-up data, small sample sizes, and overall poor research quality.
The findings of this systematic review might be used to inform research and
theory development on the psychology of elite endurance cycling.
PMID- 29346034
TI - Coagulopathy in Severe Sepsis: Interconnectivity of Coagulation and the Immune
System.
AB - BACKGROUND: Disseminated intravascular coagulation (DIC) remains a challenging
complication of infection with inadequate treatment and significant morbidity and
mortality rates. METHODS: Review of the English-language literature. RESULTS:
Disseminated intravascular coagulation arises from the immune system's response
to microbial invasion, as well as the byproducts of cell death that result from
severe sepsis. This response triggers the coagulation system through an
interconnected network of cellular and molecular signals, which developed
originally as an evolutionary mechanism intended to isolate micro-organisms via
fibrin mesh formation. However, this response has untoward consequences,
including hemorrhage and thrombosis caused by dysregulation of the coagulation
cascade and fibrinolysis system. Ultimately, diagnosis relies on clinical
findings and laboratory studies that recognize excessive activation of the
coagulation system, and treatment focuses on supportive measures and correction
of coagulation abnormalities. Clinically, DIC secondary to sepsis in the surgical
population presents a challenge both in diagnosis and in treatment. Biologically,
however, DIC epitomizes the crosstalk between signaling pathways that is
essential to normal physiology, while demonstrating the devastating consequences
when failure of local control results in systemic derangements. CONCLUSIONS: This
paper discusses the pathophysiology of coagulopathy and fibrinolysis secondary to
sepsis, the diagnostic tools available to identify the abnormalities, and the
available treatments.
PMID- 29346035
TI - Determination of 105 antibiotic, anti-inflammatory, antiparasitic agents and
tranquilizers by LC-MS/MS based on an acidic QuEChERS-like extraction.
AB - A procedure for screening 105 veterinary drugs in foods by liquid chromatography
tandem mass-spectrometry (LC-MS/MS) is presented. Its scope encompasses raw
materials of animal origin (milk, meat, fish, egg and fat) but also related
processed ingredients and finished products commonly used and manufactured by
food business operators. Due to the complexity of the matrices considered and to
efficiently deal with losses during extraction and matrix effects during MS
source ionisation, each sample was analysed twice, that is 'unspiked' and 'spiked
at the screening target concentration' using a QuEChERS-like extraction. The
entire procedure was validated according to the European Community Reference
Laboratories Residues Guidelines. False-negative and false-positive rates were
below 5% for all veterinary drugs whatever the food matrix. Effectiveness of the
procedure was further demonstrated through participation to five proficiency
tests and its ruggedness demonstrated in quality control operations by a second
laboratory.
PMID- 29346036
TI - Genetics, the Rearing Environment, and the Intergenerational Transmission of
Divorce: A Swedish National Adoption Study.
AB - We used classical and extended adoption designs in Swedish registries to
disentangle genetic and rearing-environment influences on the intergenerational
transmission of divorce. In classical adoption analyses, adoptees ( n = 19,715)
resembled their biological parents, rather than their adoptive parents, in their
history of divorce. In extended adoption analyses, offspring ( n = 82,698)
resembled their not-lived-with fathers and their lived-with mothers. There was
stronger resemblance to lived-with mothers, providing indirect evidence of
rearing-environment influences on the intergenerational transmission of divorce.
The heritability of divorce assessed across generations was 0.13. We attempted to
replicate our findings using within-generation data from adoptive and biological
siblings ( ns = 8,523-53,097). Adoptees resembled their biological, not adoptive,
siblings in their history of divorce. Thus, there was consistent evidence that
genetic factors contributed to the intergenerational transmission of divorce but
weaker evidence for a rearing-environment effect of divorce. Within-generation
data from siblings supported these conclusions.
PMID- 29346037
TI - Development of an ultrasensitive PCR assay for polycyclic musk determination in
fish.
AB - Polycyclic musks (PCMs) in the aquatic environment and organisms have become an
emerging environmental issue because of their potential risk. The most used
method for polycyclic musk determination is gas chromatography-mass spectrometry
(GC-MS) with different sample extractions, which are somewhat expensive to
operate, complex and laborious. In this study, a novel and ultrasensitive real
time polymerase chain reaction (PCR) assay with multiple signal amplification of
carboxylic-DNA by gold nanoparticle-polyamidoamine conjugation (Au-PAMAM) was
developed for determining polycyclic musks in fish. Hapten and immunogen were
specially prepared. Polyclonal antibodies were produced based on the optimal
immunisation, and the antibodies were characterised. Due to PAMAM's unique
nanostructure of numerous functional amino groups, polyclonal antibody and
carboxylic-DNA were immobilised by Au-PAMAM conjugation to develop the antibody
Au-PAMAM-DNA probes, which were used as a signal DNA amplifier in the PCR system.
Compared with real-time immuno-PCR, this biological probe-amplified immuno-PCR
(BPAI-PCR) assay had higher sensitivity due to the probes' higher ratio of signal
DNA. Finally, the BPAI-PCR assay was applied to analyse AHTN (7-acetyl
1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene,Tonalide) concentrations in
fish samples in the range from 1 pg/L to 10 ng/L, giving an of LOD 0.61 pg/L. In
general, due to the specificity of the antibody and novel nanoprobe design, this
BPAI-PCR assay provided a potential way for trace analysis of AHTN in the aquatic
organisms. The high concentrations of AHTN found in cultivated fish should
encourage further toxicological studies.
PMID- 29346038
TI - Smartphone Applications for Amblyopia Treatment: A Review of Current Apps and
Professional Involvement.
AB - OBJECTIVES: The objective of this study was to review games for amblyopia (lazy
eye) that are commercially available in mobile applications (apps) stores and
assess the involvement of eye care professionals in their development. MATERIALS
AND METHODS: The Google play store and the Apple iTunes store were searched in
July 2017 and updated in September 2017 for amblyopia games using the terms
amblyopia, lazy eye, amblyopia therapy, lazy eye therapy, lazy eye exercises,
amblyopia exercises, lazy eye games, and amblyopia games. General ophthalmology
or optometry apps and apps in languages other than English were excluded.
RESULTS: A total of 42 games were identified, 12 Android only (28%), 20 iOS only
(48%), and 10 (24%) both Android and iOS. Most of the games were available under
the medical category (60%). Most of the games were released in 2015. The price of
the games ranged from $0.00 to $32.00 (USD). Nearly half of the games (45%) were
to be played binocularly either using red-green goggles (38%) or a virtual
reality set (7%). Only 7% of the games had explicitly documented the involvement
of eye care professionals during game development. Only one game (app) was
developed in collaboration with a research group and a children's hospital.
CONCLUSIONS: This study identified that most of the currently available games do
not have eye care professional input. An establishment of the quality assurance
by a body of qualified eye care professionals could enhance the confidence of
patients and clinicians using the game.
PMID- 29346039
TI - Evaluation of a French Regional Telemedicine Network Dedicated to Neurological
Emergencies: A 14-Year Study.
AB - BACKGROUND: Equality in healthcare between urban and rural areas is problematic
in France. Telemedicine networks are expected to improve equality in expertise
assessment. We aimed to evaluate the use and impact of a regional rural French
telemedicine network, dedicated to medical and surgical neurological emergencies,
on interhospital patient transfers. METHODS: Eight community hospital emergency
departments were remotely connected to the only university hospital in Franche
Comte, France. We prospectively obtained data from all patients consecutively
admitted to emergency care departments in the region and who received medical or
neurosurgical expertise by telemedicine from January 2002 to December 2015. The
reasons for requesting expertise, number of requested neurological opinions, and
interhospital patient transfers were analyzed. Economic savings were determined
by estimating the cost of avoided transfers. RESULTS: A total of 23,710 patients
had telemedicine consultations in the region. The network was used by every
community hospital (independently of the existence of local neurological teams).
These consultations were overwhelmingly for cases of stroke (30%) and head or
spinal injuries (36%). Cerebral tumors represented 9% of teleconsultations. In
2015, 75% of patients admitted to the remote hospitals that did not have onsite
neurological expertise nevertheless received neurovascular tele-expertise. The
rate of thrombolyzed patients dramatically increased within 13 years regionally
(9.9%) and 33.5% of thrombolyses were performed by telemedicine. The number of
patients examined by telemedicine and admitted for head or spinal injuries also
increased over the 13-year period (12% vs. 21%). Secondary interhospital
transfers were halved for both pathologies. The estimated saving is ~?3.5
million. CONCLUSION: Telemedicine networks facilitate acute-phase neurological
assessment and prevent unnecessary secondary interhospital transfers.
PMID- 29346040
TI - Bevacizumab Maintenance Versus No Maintenance During Chemotherapy-Free Intervals
in Metastatic Colorectal Cancer: A Randomized Phase III Trial (PRODIGE 9).
AB - Purpose Conflicting results are reported for maintenance treatment with
bevacizumab during chemotherapy-free intervals (CFI) in metastatic colorectal
cancer after induction chemotherapy. Patients and Methods In this open-label,
phase III, randomized controlled trial, we compared the tumor control duration
(TCD) observed with bevacizumab maintenance and with no treatment (observation)
during CFI subsequent to induction chemotherapy with 12 cycles of fluorouracil,
leucovorin, and irinotecan plus bevacizumab. After disease progression, the
induction regimen was repeated for eight cycles, followed by a new CFI. Results
From March 2010 to July 2013, 491 patients were randomly assigned. Disease
progression or death occurred during induction chemotherapy in 85 patients (17%);
261 patients (53%) had at least one reinduction, 107 (22%) had two reinductions,
and 56 (11%) had three or more reinductions. The median TCD was 15 months in both
groups; the median progression-free survival (PFS) from randomization was 9.2 and
8.9 months in the maintenance group and observation groups, respectively. The TCD
observed in both groups was higher compared with the TCD hypotheses of the trial.
The median overall survival (OS) was 21.7 and 22.0 months in the maintenance and
observation groups, respectively. In the per-protocol population, defined as
patients with at least one reinduction after the first progression, the median
duration of the first CFI was 4.3 months in both arms; the median TCD was 17.8
and 23.3 months ( P = .339), the median PFS was 9.9 and 9.5 months, and the
median OS was 27.6 and 28.5 months in the maintenance and observation groups,
respectively. Multivariable analysis revealed that female gender, WHO performance
status >= 2, and unresected primary tumors were associated with a shorter TCD.
Conclusion Bevacizumab maintenance monotherapy did not improve TCD, CFI duration,
PFS, or OS.
PMID- 29346041
TI - Post-Treatment Mortality After Surgery and Stereotactic Body Radiotherapy for
Early-Stage Non-Small-Cell Lung Cancer.
AB - Purpose In early-stage non-small cell lung cancer (NSCLC), post-treatment
mortality may influence the comparative effectiveness of surgery and stereotactic
body radiotherapy (SBRT), with implications for shared decision making among high
risk surgical candidates. We analyzed early mortality after these interventions
using the National Cancer Database. Patients and Methods We abstracted patients
with cT1-T2a, N0, M0 NSCLC diagnosed between 2004 and 2013 undergoing either
surgery or SBRT. Thirty-day and 90-day post-treatment mortality rates were
calculated and compared using Cox regression and propensity score-matched
analyses. Results We identified 76,623 patients who underwent surgery (78%
lobectomy, 20% sublobar resection, 2% pneumonectomy) and 8,216 patients who
received SBRT. In the unmatched cohort, mortality rates were moderately increased
with surgery versus SBRT (30 days, 2.07% v 0.73% [absolute difference (Delta),
1.34%]; P < .001; 90 days, 3.59% v 2.93% [Delta, 0.66%]; P < .001). Among the
27,200 propensity score-matched patients, these differences increased (30 days,
2.41% v 0.79% [Delta, 1.62%]; P < .001; 90 days, 4.23% v 2.82% [Delta, 1.41%]; P
< .001). Differences in mortality between surgery and SBRT increased with age,
with interaction P < .001 at both 30 days and 90 days (71 to 75 years old: 30-day
Delta, 1.87%; 90-day Delta, 2.02%; 76 to 80 years old: 30-day Delta, 2.80%; 90
day Delta, 2.59%; > 80 years old: 30-day Delta, 3.03%; 90-day Delta, 3.67%; all P
<= .001). Compared with SBRT, surgical mortality rates were higher with increased
extent of resection (30-day and 90-day multivariate hazard ratio for mortality:
sublobar resection, 2.85 and 1.37; lobectomy, 3.65 and 1.60; pneumonectomy, 14.5
and 5.66; all P < 0.001). Conclusion Differences in 30- and 90-day post-treatment
mortality between surgery and SBRT increased as a function of age, with the
largest differences in favor of SBRT observed among patients older than 70 years.
These representative mortality data may inform shared decision making among
patients with early-stage NSCLC who are eligible for both interventions.
PMID- 29346042
TI - Treatment of Malignant Pleural Mesothelioma: American Society of Clinical
Oncology Clinical Practice Guideline.
AB - Purpose To provide evidence-based recommendations to practicing physicians and
others on the management of malignant pleural mesothelioma. Methods ASCO convened
an Expert Panel of medical oncology, thoracic surgery, radiation oncology,
pulmonary, pathology, imaging, and advocacy experts to conduct a literature
search, which included systematic reviews, meta-analyses, randomized controlled
trials, and prospective and retrospective comparative observational studies
published from 1990 through 2017. Outcomes of interest included survival, disease
free or recurrence-free survival, and quality of life. Expert Panel members used
available evidence and informal consensus to develop evidence-based guideline
recommendations. Results The literature search identified 222 relevant studies to
inform the evidence base for this guideline. Recommendations Evidence-based
recommendations were developed for diagnosis, staging, chemotherapy, surgical
cytoreduction, radiation therapy, and multimodality therapy in patients with
malignant pleural mesothelioma. Additional information is available at
www.asco.org/thoracic-cancer-guidelines and www.asco.org/guidelineswiki .
PMID- 29346043
TI - Analysis of Margin Classification Systems for Assessing the Risk of Local
Recurrence After Soft Tissue Sarcoma Resection.
AB - Purpose To compare the ability of margin classification systems to determine
local recurrence (LR) risk after soft tissue sarcoma (STS) resection. Methods Two
thousand two hundred seventeen patients with nonmetastatic extremity and truncal
STS treated with surgical resection and multidisciplinary consideration of
perioperative radiotherapy were retrospectively reviewed. Margins were coded by
residual tumor (R) classification (in which microscopic tumor at inked margin
defines R1), the R+1mm classification (in which microscopic tumor within 1 mm of
ink defines R1), and the Toronto Margin Context Classification (TMCC; in which
positive margins are separated into planned close but positive at critical
structures, positive after whoops re-excision, and inadvertent positive margins).
Multivariate competing risk regression models were created. Results By R
classification, LR rates at 10-year follow-up were 8%, 21%, and 44% in R0, R1,
and R2, respectively. R+1mm classification resulted in increased R1 margins (726
v 278, P < .001), but led to decreased LR for R1 margins without changing R0 LR;
for R0, the 10-year LR rate was 8% (range, 7% to 10%); for R1, the 10-year LR
rate was 12% (10% to 15%) . The TMCC also showed various LR rates among its tiers
( P < .001). LR rates for positive margins on critical structures were not
different from R0 at 10 years (11% v 8%, P = .18), whereas inadvertent positive
margins had high LR (5-year, 28% [95% CI, 19% to 37%]; 10-year, 35% [95% CI, 25%
to 46%]; P < .001). Conclusion The R classification identified three distinct
risk levels for LR in STS. An R+1mm classification reduced LR differences between
R1 and R0, suggesting that a negative but < 1-mm margin may be adequate with
multidisciplinary treatment. The TMCC provides additional stratification of
positive margins that may aid in surgical planning and patient education.
PMID- 29346045
TI - In This Issue * February 1, 2018.
PMID- 29346044
TI - Clinical features, treatment, and outcomes of cutaneous and oral squamous cell
carcinoma in avian species.
AB - OBJECTIVE To determine the clinical features, treatment, and outcomes of
treatment for oral and cutaneous squamous cell carcinoma (SCC) in avian species.
DESIGN Retrospective case series with nested cohort study. ANIMALS 87 client
owned birds of various species with histologically confirmed SCC of the skin or
oral cavity. PROCEDURES Clinicians entered case information through an online
survey tool. Data were collected regarding patient signalment, concurrent
conditions, treatments, adverse effects, and clinical outcomes. Relationships
were examined between complete excision and partial or complete response.
Survival analysis was performed to compare outcomes among groupings of
therapeutic approaches. RESULTS Only 7 of 64 (11%) birds for which full outcome
data were available had complete remission of SCC; 53 (83%) had progressive
disease, were euthanized, or died of the disease. The unadjusted OR for partial
or complete response following complete tumor excision (vs other treatment
approaches) was 6.9 (95% confidence interval [CI], 1.8 to 25.8). Risk of death
was 62% lower (hazard ratio, 0.38; 95% CI, 0.19 to 0.77) for birds that underwent
complete excision versus conservative treatment. Median survival time from
initial evaluation for birds receiving complete excision was 628 days (95% CI,
210 to 1,008 days), compared with 171 days (95% CI, 89 to 286 days) for birds
receiving monitoring with or without conservative treatment. Birds receiving any
other additional treatment had a median survival time of 357 days (95% CI, 143 to
562 days). CONCLUSIONS AND CLINICAL RELEVANCE For birds with SCC, complete
excision was the only treatment approach significantly associated with complete
or partial response and increased survival time.
PMID- 29346046
TI - Ultrasonographic characteristics of the reproductive tract and serum progesterone
and estradiol concentrations in captive female red wolves (Canis rufus) with and
without reproductive tract disease.
AB - OBJECTIVE To describe ultrasonographic characteristics of the reproductive tract
and serum progesterone and estradiol concentrations in captive female red wolves
(Canis rufus) with and without reproductive tract disease. DESIGN Prospective
study. ANIMALS 13 adult female red wolves. PROCEDURES Wolves with varying parity
and history of contraceptive treatment were anesthetized to facilitate
ultrasonographic examination and measurement of the reproductive tract and blood
collection for determination of serum progesterone and estradiol concentrations
in December 2011 and June 2012. Additionally, during the December evaluation,
fine-needle aspirate samples of the uterus were obtained for cytologic
evaluation. Measurements were compared between wolves with and without
reproductive tract disease and between wolves that had and had not received a
contraceptive. RESULTS 7 of 13 wolves had or developed reproductive tract disease
during the study. Ranges for measurements of reproductive tract structures
overlapped between ultrasonographically normal and abnormal tracts, but
measurements for abnormal tracts were generally greater than those for normal
tracts. The ultrasonographic diagnosis was consistent with the histologic
diagnosis for reproductive tracts obtained from wolves that were sterilized, were
euthanized, or died during the study. Cytologic results for fine-needle aspirate
samples of the uterus and serum progesterone and estradiol concentrations were
unable to distinguish wolves with and without reproductive tract disease.
Reproductive tract disease was not associated with parity or contraceptive
administration. CONCLUSIONS AND CLINICAL RELEVANCE The ultrasonographic images,
reproductive tract measurements, and descriptions of reproductive tract lesions
provided in this study can be used as diagnostic guidelines for the treatment and
management of red wolves with reproductive tract disease.
PMID- 29346047
TI - Cultivating our next generation of leaders.
PMID- 29346048
TI - Risk factors and prognostic indicators for surgical outcome of dogs with
esophageal foreign body obstructions.
AB - OBJECTIVE To determine risk factors for surgical intervention, complications, and
outcome in dogs with an esophageal foreign body (EFB). DESIGN Retrospective
observational study. ANIMALS 224 incidents of EFB in 223 dogs evaluated at a
veterinary teaching hospital from 1995 through 2014. PROCEDURES Hospital records
were reviewed to collect data regarding signalment, history, clinical signs, EFB
type and location, procedures, complications, and outcomes. Breed distributions
were compared between dogs with EFB and the entire canine patient population
during the study period. Variables were tested for associations with each other
and with outcomes. RESULTS Terrier breeds were most common (71/233 [30.5%]).
Duration of EFB entrapment, body weight, anorexia, lethargy, rectal temperature,
and esophageal perforation were associated with the need for surgical
intervention. Older age, longer duration of EFB entrapment, and perforation were
associated with a poorer prognosis. Endoscopic retrieval or advancement into the
stomach was successful for 183 of 219 (83.6%) EFBs, and 16 of 143 (11.2%)
entrapments resulted in postprocedural esophageal stricture. Overall median
duration of hospitalization was brief (1 day), and the need for surgical
intervention was associated with a longer duration. Overall mortality rate was
5.4% (12/223); 90 of 102 (88.2%) dogs with a median follow-up period of 27 months
after EFB treatment had an excellent outcome. CONCLUSIONS AND CLINICAL RELEVANCE
Study findings suggested that endoscopic EFB retrieval remains the initial
treatment option of choice for affected dogs, provided that esophageal
perforation does not necessitate surgical intervention. Although esophageal
stricture formation was the most common complication, the overall rate of this
outcome was low.
PMID- 29346049
TI - Microphthalmia, corneal dermoids, and congenital anomalies resembling Goldenhar
syndrome in a cat.
AB - CASE DESCRIPTION An 18-month-old spayed female domestic shorthair cat was
evaluated because of conjunctivitis and skin-fold dermatitis secondary to
bilateral microphthalmia, corneal dermoids, and ankyloblepharon. CLINICAL
FINDINGS Physical examination revealed bilateral microphthalmia, bilaterally
symmetrical corneal dermoids, ankyloblepharon, superior and inferior entropion,
prognathism, and facial asymmetry with deviation of the nasal septum. Computed
tomography revealed malformed, thickened bony orbits with mineralization of the
orbital ligament bilaterally. Moderate rightward deviation of the nasal septum
and ventral nasal meatus was also evident, with no identifiable maxillary
sinuses. Results of MRI of the brain were unremarkable. Abdominal ultrasonography
showed an irregularly marginated left kidney and a right kidney defect suggestive
of chronic renal infarction. An abnormal, well-demarcated, focally thickened
region of the muscularis externa of the jejunum was also evident. TREATMENT AND
OUTCOME Transpalpebral enucleation was performed bilaterally. Histologic
examination of ocular tissues confirmed the corneal dermoids and microphthalmia
with anterior and posterior segment dysgenesis and cataracts in both eyes. Ocular
discomfort resolved after postoperative recovery, and follow-up revealed that the
patient's activity level and quality of life were excellent. No clinical signs of
upper respiratory, urinary, or gastrointestinal tract disease were observed
during the approximately 3.5-year follow-up period. CLINICAL RELEVANCE The
congenital abnormalities observed resembled those described for human patients
with Goldenhar syndrome, and the outcome of treatment was favorable. This report
may prompt clinicians to consider this diagnosis when evaluating young cats with
similar clinical signs.
PMID- 29346050
TI - Diagnosis and management of inflammatory bowel disease in a harpy eagle (Harpia
harpyja) with suspected fenbendazole toxicosis.
AB - CASE DESCRIPTION A 14-year-old 4.1-kg (9.02-lb) male harpy eagle (Harpia harpyja)
was evaluated because of vomiting, anorexia, lethargy, and weight loss (decrease
of 0.35 kg [0.77 lb]) of 4 weeks' duration. The bird had previously been treated
orally with fenbendazole after the initial onset of clinical signs. CLINICAL
FINDINGS An initial CBC revealed marked heteropenia and anemia, but whole-body
contrast-enhanced CT images and other diagnostic test findings were unremarkable.
Clinical signs persisted, and additional diagnostic testing failed to reveal the
cause. During celiotomy, a biopsy specimen of the duodenum was obtained for
histologic examination, which revealed lymphoplasmacytic inflammation, consistent
with inflammatory bowel disease (IBD). TREATMENT AND OUTCOME Prior to
histopathologic diagnosis of IBD, barium sulfate administered via gavage resulted
in a temporary improvement of clinical signs. Following diagnosis of IBD,
corticosteroid administration was initiated in conjunction with antifungal
prophylaxis. Cessation of vomiting and a return to normal appetite occurred
within 3 days. Fifteen months after cessation of corticosteroid treatment, the
eagle continued to do well. CLINICAL RELEVANCE To our knowledge, this was the
first report of diagnosis and management of IBD in an avian species. For the
eagle of the present report, results of several diagnostic tests increased
clinical suspicion of IBD, but histologic examination of an intestinal biopsy
specimen was required for definitive diagnosis. Although successful in this case,
steroid administration in avian species must be carefully considered. Conclusive
evidence of fenbendazole toxicosis was not obtained, although it was highly
suspected in this bird.
PMID- 29346051
TI - Diagnosis, treatment, and outcome of and risk factors for ophthalmic disease in
leopard geckos (Eublepharis macularius) at a veterinary teaching hospital: 52
cases (1985-2013).
AB - OBJECTIVE To describe diagnosis, treatment, and outcome of and risk factors for
ophthalmic disease in leopard geckos (Eublepharis macularius) evaluated at a
veterinary teaching hospital. DESIGN Retrospective case series. ANIMALS 112 of
144 (78%) leopard geckos that were evaluated at a veterinary teaching hospital in
January 1985 through October 2013 and for which sufficient medical record
information was available. PROCEDURES Information from medical records was used
to identify leopard geckos with ophthalmic disease, characterize cases, and
determine risk factors for the presence of ophthalmic disease. RESULTS Of the 112
leopard geckos, 52 (46%) had ophthalmic disease (mainly corneal or conjunctival
disease). Female geckos were less likely to have ophthalmic disease, and there
was a positive association between increasing age and ophthalmic disease. Use of
a paper towel substrate, absence of any heat source, and lack of vitamin A
supplementation were positively associated with a diagnosis of ophthalmic
disease. Head dysecdysis was the only concurrent disorder significantly
associated with ophthalmic disease. At necropsy, 5 affected leopard geckos had
squamous metaplasia of the conjunctivae. CONCLUSIONS AND CLINICAL RELEVANCE
Results indicated that ophthalmic disease is a common finding in leopard geckos.
The cause of ocular surface disease in leopard geckos may be multifactorial, and
hypovitaminosis A may be an important risk factor. Although animals receiving
supplemental vitamin A were less likely to have ophthalmic disease, further
understanding is required regarding the metabolism of and nutritional
requirements for vitamin A in leopard geckos.
PMID- 29346052
TI - Pathology in Practice.
PMID- 29346053
TI - What Is Your Diagnosis?
PMID- 29346055
TI - Pathology in Practice.
PMID- 29346056
TI - Esophageal leiomyoma in a dog causing esophageal distension and treated by
transcardial placement of a self-expanding, covered, nitinol esophageal stent.
AB - CASE DESCRIPTION A 10-year-old spayed female Rottweiler was referred for
evaluation because of a 2-month history of regurgitation and weight loss, despite
no apparent change in appetite. The dog had received antiemetic and antacid
treatment, without improvement. CLINICAL FINDINGS Physical examination revealed a
low body condition score (2/5), but other findings were unremarkable. Diffuse,
global esophageal dilatation was noted on plain thoracic radiographs, and normal
motility was confirmed through videofluoroscopic evaluation of swallowing.
Transhepatic ultrasonographic and CT examination revealed a circumferential,
intraparietal lesion in the distal portion of the esophagus causing distal
esophageal or cardial subobstruction and no metastases. Incisional biopsy of the
lesion was performed, and findings of histologic examination supported a
diagnosis of esophageal leiomyoma. TREATMENT AND OUTCOME In view of numerous
possible complications associated with esophageal surgery, the decision was made
to palliatively treat the dog by transcardial placement of a self-expanding,
covered, nitinol esophageal stent under endoscopic guidance. Two weeks after
stent placement, radiography revealed complete migration of the stent into the
gastric lumen. Gastrotomy was performed, and the stent was replaced and fixed in
place. Twenty-four months after initial stent placement, the dog had a healthy
body condition and remained free of previous clinical signs. CLINICAL RELEVANCE
Diffuse benign muscular neoplasia should be considered as a differential
diagnosis for acquired esophageal dilatation in adult and elderly dogs. In the
dog of this report, transcardial stent placement resulted in resolution of the
clinical signs, with no apparent adverse effect on digestive function. The
described procedure could be beneficial for nonsurgical treatment of benign
esophageal tumors in dogs.
PMID- 29346057
TI - Anesthesia Case of the Month.
PMID- 29346058
TI - How Much Do We Spend? Creating Historical Estimates of Public Health Expenditures
in the United States at the Federal, State, and Local Levels.
AB - The United States has a complex governmental public health system. Agencies at
the federal, state, and local levels all contribute to the protection and
promotion of the population's health. Whether the modern public health system is
well situated to deliver essential public health services, however, is an open
question. In some part, its readiness relates to how agencies are funded and to
what ends. A mix of Federalism, home rule, and happenstance has contributed to a
siloed funding system in the United States, whereby health agencies are given
particular dollars for particular tasks. Little discretionary funding remains.
Furthermore, tracking how much is spent, by whom, and on what is notoriously
challenging. This review both outlines the challenges associated with estimating
public health spending and explains the known sources of funding that are used to
estimate and demonstrate the value of public health spending.
PMID- 29346059
TI - Fermented Extraction of Citrus unshiu Peel Inhibits Viability and Migration of
Human Pancreatic Cancers.
AB - Pancreatic cancer is one of the most dangerous cancers with high mortality rates.
Despite continuous efforts, there has been limited improvement in its prognosis.
In this study, we prepared fermented extract of Citrus unshiu peel (fCUP) from
the by-product after juice processing and then examined the anticancer effects of
fCUP on human pancreatic cancer cells. Treatment with fCUP inhibited the growth
of human pancreatic cancer cells through induction of caspase-3 cleavage both in
vitro and in vivo. Treatment with fCUP also blocked the migration of human
pancreatic cancer cells through activation of intracellular signaling pathways
such as MKK3/6 and P38. In contrast, treatment with fCUP did not inhibit growth
and migration of human umbilical vein endothelial cells. In addition, we found
that fCUP mainly consisted of aboriginal compounds, narirutin and hesperidin, as
well as newly generated compounds, naringenin and hesperetin. In silico analysis
showed that naringenin and hesperetin were the unique modules related to
anticancer effect. Furthermore, fCUP exhibited the anticancer effects in in vivo
xenograft models. Collectively, these results suggest that fCUP might have the
potential to be developed into an effective anticancer drug for pancreatic
cancers without causing adverse side-effects.
PMID- 29346060
TI - A Combination with Probiotic Complex, Zinc, and Coenzyme Q10 Attenuates
Autoimmune Arthritis by Regulation of Th17/Treg Balance.
AB - Probiotic complex, zinc, and coenzyme Q10 (CoQ10) are recognized dietary
supplements with an anti-inflammatory role. Although these supplementations are
individually known to benefit rheumatoid arthritis (RA), there is no evidence
suggesting any synergic effect. The primary goal of this study is to determine
whether probiotic complex, zinc, and CoQ10 attenuate the development of collagen
induced arthritis (CIA). The combination of probiotic complex, zinc, and CoQ10
reduced CIA severity by downregulating the levels of IgG, IgG1, and IgG2a in
serum. Joint inflammation, bone destruction, and cartilage damage were also
improved by the complex. There was a decrease in the expression of tumor necrosis
factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-17, and vascular endothelial
growth factor (VEGF) in the joint synovium. The balance between helper T 17
(Th17) cells and regulatory T (Treg) cells was shown to be controlled
reciprocally by the complex. These findings suggest that the combination of
probiotic complex, zinc, and CoQ10 can ameliorate the development of CIA by
inhibiting the expression of proinflammatory cytokines, and is thus an important
therapeutic candidate for RA treatment.
PMID- 29346061
TI - Two Cases of Dengue Fever Imported from Egypt to Russia, 2017.
AB - In 2017, two cases of dengue fever were imported from Hurghada, Egypt, where
dengue fever was not considered endemic, to Moscow. These cases show how
emergence of dengue fever in popular resort regions on the coast of the Red Sea
can spread infection to countries where it is not endemic.
PMID- 29346062
TI - Television Viewing Time, Physical Activity, and Mortality Among African
Americans.
AB - BACKGROUND: Prolonged television viewing time, a marker of sedentary activity, is
independently associated with increased all-cause mortality; however, this
association has rarely been studied in African Americans. The objective of our
study was to examine the association between television viewing time and
mortality among African Americans by using data from the Jackson Heart Study
(JHS). METHODS: We studied 5,289 participants from the JHS study who reported
television viewing time (h/day) in the JHS baseline questionnaire from 2000
through 2004. Using multivariable Cox regression models adjusted for age, sex,
smoking, alcohol use, physical activity, nutrition, prevalent coronary heart
disease, chronic kidney disease, diabetes, and hypertension, we computed hazard
ratios to examine the association between television viewing time (<=2 h/day, 2-4
h/day, and >=4 h/day) and mortality. RESULTS: Participants had a mean age of 55
years, and 64% were women. After a median follow-up of 9.9 years (interquartile
range, 9.0-10.7), 615 deaths occurred (data analysis conducted in 2017). Hazard
ratios for mortality were 1.08 (0.86-1.37) for television time of 2 to 4 hours
per day and 1.48 (95% CI: 1.19-1.83) for television time of greater than or equal
to 4 hours per day when compared with those who watched television less than 2
hours per day (P trend = .002). When we restricted analyses to those who
performed leisure-time activities, the hazard ratios for mortality were 1.10 (95%
CI, 0.84-1.45) for television viewing of 2 to 4 hours per day and 1.45 (95% CI,
1.13-1.86) for more than 4 hours per day compared with the less than 2 hours per
day. CONCLUSION: Our findings suggest that greater television viewing time, even
among those who perform leisure-time physical activities, is associated with
increased all-cause mortality among African Americans. Thus, it may serve as an
indicator of a sedentary lifestyle with potential for intervention.
PMID- 29346063
TI - Linking Data From Health Surveys and Electronic Health Records: A Demonstration
Project in Two Chicago Health Center Clinics.
AB - INTRODUCTION: Monitoring and understanding population health requires conducting
health-related surveys and surveillance. The objective of our study was to assess
whether data from self-administered surveys could be collected electronically
from patients in urban, primary-care, safety-net clinics and subsequently linked
and compared with the same patients' electronic health records (EHRs). METHODS:
Data from self-administered surveys were collected electronically from a
convenience sample of 527 patients at 2 Chicago health centers from September
through November, 2014. Survey data were linked to EHRs. RESULTS: A total of 251
(47.6%) patients who completed the survey consented to having their responses
linked to their EHRs. Consenting participants were older, more likely to report
fair or poor health, and took longer to complete the survey than those who did
not consent. For 8 of 18 categorical variables, overall percentage of agreement
between survey data and EHR data exceeded 80% (sex, race/ethnicity, pneumococcal
vaccination, self-reported body mass index [BMI], diabetes, high blood pressure,
medication for high blood pressure, and hyperlipidemia), and of these, the level
of agreement was good or excellent (kappa >=0.64) except for pneumococcal
vaccination (kappa = 0.40) and hyperlipidemia (kappa = 0.47). Of 7 continuous
variables, agreement was substantial for age and weight (concordance coefficients
>=0.95); however, with the exception of calculated survey BMI and EHR-BMI
(concordance coefficient = 0.88), all other continuous variables had poor
agreement. CONCLUSIONS: Self-administered and web-based surveys can be completed
in urban, primary-care, safety-net clinics and linked to EHRs. Linking survey and
EHR data can enhance public health surveillance by validating self-reported data,
completing gaps in patient data, and extending sample sizes obtained through
current methods. This approach will require promoting and sustaining patient
involvement.
PMID- 29346064
TI - Using Two Disability Measures to Compare Physical Inactivity Among US Adults With
Disabilities.
AB - Prevalence of health behaviors among adults with disabilities may vary by
disability measure. We used data from the 2011-2015 National Health Interview
Survey to estimate prevalence of physical inactivity by disability status using 2
measures of disability: Basic Actions Difficulty questions (BADQ) and a standard
6-question measure (6Q). Disability prevalence (BADQ, 31.1%; 6Q, 17.5%) and
inactivity prevalence among adults with disability (BADQ, 42.9%; 6Q, 52.5%) and
without disability (BADQ, 24.3%; 6Q, 26.2%) varied by measure; however, both
measures highlight inactivity disparities for adults with disability. Disability
measures influence physical inactivity estimates and are important for guiding
surveillance and health promotion activities for adults with disabilities.
PMID- 29346065
TI - Accuracy of Principal and Teacher Knowledge of School District Policies on Sun
Protection in California Elementary Schools.
AB - INTRODUCTION: Policy is a key aspect of school-based efforts to prevent skin
cancer. We explored the extent and accuracy of knowledge among principals and
teachers in California public school districts about the elements specified in
their district's written sun safety policy. METHODS: The sample consisted of
California public school districts that subscribed to the California School
Boards Association, had an elementary school, adopted Board Policy 5141.7 for sun
safety, and posted it online. The content of each policy was coded. Principals (n
= 118) and teachers (n = 113) in elementary schools were recruited from September
2013 through December 2015 and completed a survey on sun protection policies and
practices from January 2014 through April 2016. RESULTS: Only 38 of 117
principals (32.5%) were aware that their school district had a sun protection
policy. A smaller percentage of teachers (13 of 109; 11.9%) than principals were
aware of the policy (F108 = 12.76, P < .001). We found greater awareness of the
policy among principals and teachers who had more years of experience working in
public education (odds ratio [OR] = 1.05, F106 = 4.71, P = .03) and worked in
schools with more non-Hispanic white students (OR = 7.65, F109 = 8.61, P = .004)
and fewer Hispanic students (OR = 0.28, F109 = 4.27, P = .04). CONCLUSION: Policy
adoption is an important step in implementing sun safety practices in schools,
but districts may need more effective means of informing school principals and
teachers of sun safety policies. Implementation will lag without clear
understanding of the policy's content by school personnel.
PMID- 29346066
TI - Expression of autophagy related genes in chronic lymphocytic leukemia is
associated with disease course.
AB - Autophagy leads cells to different fates in various cell types and under diverse
contexts. Chronic lymphocytic leukemia (CLL), an incurable hematologic neoplasm,
has highly variable course and its heterogeneity prompts interest in exploring
autophagic trajectories in CLL. We detected the mRNA levels of two autophagy
related genes, BECN1 and ATG5, assessed the association between expression levels
and clinical characteristics, and did survival analysis. One hundred and six
patients with CLL and fifty healthy controls were enrolled in the present study.
CLL samples were found higher expression levels of BECN1 and ATG5 mRNA compared
with healthy controls. Further confirmation at the protein level performed in a
small cohort of patients, which included Beclin1, ATG5 and LC3-II showed the same
trend. What's more, high expression at the mRNA level correlated with early Binet
stage, isolated 13q deletion and negative CD38, which were associated with favor
prognosis, suggesting that autophagy differs in CLL due to the presence of
heterogeneity and high levels of these two genes may reflect better outcomes.
Survival analysis did show patients with high expression of ATG5 mRNA had longer
treatment free survival from the date of sampling.
PMID- 29346067
TI - The association between child maltreatment and adult poverty - A systematic
review of longitudinal research.
AB - Child maltreatment is a global problem affecting millions of children and is
associated with an array of cumulative negative outcomes later in life, including
unemployment and financial difficulties. Although establishing child maltreatment
as a causal mechanism for adult economic outcomes is fraught with difficulty,
understanding the relationship between the two is essential to reducing such
inequality. This paper presents findings from a systematic review of longitudinal
research examining experiences of child maltreatment and economic outcomes in
adulthood. A systematic search of seven databases found twelve eligible
retrospective and prospective cohort studies. From the available evidence, there
was a relatively clear relationship between 'child maltreatment' and poorer
economic outcomes such as reduced income, unemployment, lower level of job skill
and fewer assets, over and above the influence of family of origin socio-economic
status. Despite an extremely limited evidence base, neglect had a consistent
relationship with a number of long-term economic outcomes, while physical abuse
has a more consistent relationship with income and employment. Studies examining
sexual abuse found less of an association with income and employment, although
they did find a relationship other outcomes such as sickness absence, assets,
welfare receipt and financial insecurity. Nonetheless, all twelve studies showed
some association between at least one maltreatment type and at least one economic
measure. The task for future research is to clarify the relationship between
specific maltreatment types and specific economic outcomes, taking account of how
this may be influenced by gender and life course stage.
PMID- 29346068
TI - Prevalence of hypertension and prehypertension among a coastal population in
south India: baseline findings from a population-based health registry project in
Kerala.
PMID- 29346069
TI - The prevalence and influencing factors for child neglect in a rural area of Anhui
province: a 2-year follow-up study.
AB - OBJECTIVES: The purpose of the current study was to identify the change of
prevalence and influencing factors for child neglect in a rural area of Anhui
province through the 2-year follow-up study. STUDY DESIGN: Longitudinal study
with 2-year follow-up. METHODS: Analyses were based on data from a longitudinal
study, performed in five elementary schools and three secondary schools in
Changfeng County. A total of 816 children aged between 7 and 16 years completed
the three assessments during the period of 2009-2011. Generalized estimating
equations (GEEs) were applied to identify the influencing factors of child
neglect. RESULTS: The prevalence of child neglect was 67.8%, 56.6%, and 57.7% at
the three assessments, respectively. There were 272 children (33.3%) having
consistently experiencing neglect during three assessments and 106 (13.0%)
children had not suffered from neglect during three assessments. Among 553
participants who experienced neglect at the first assessment, 105 (19.0%)
children no longer met the diagnosis at the next two assessments. Fifty-two
children who did not suffer from neglect at the first assessment experienced
neglect at the final assessment. The results of GEEs showed that child neglect
was clearly associated with age (odds ratio [OR] = 0.95, 95% confidence interval
[CI] = 0.92-0.99, P = 0.016), male gender (OR = 1.20, 95% CI = 1.00-1.43, P =
0.047), siblings (OR = 1.26, 95% CI = 1.03-1.55, P = 0.028), parental marital
disruption (OR = 2.02, 95% CI = 1.09-3.78, P = 0.027), left-behind status (OR =
1.26, 95% CI = 1.06-1.49, P = 0.008), severe family dysfunction (OR = 1.46, 95%
CI = 1.03-2.07, P = 0.035), quality of life (OR = 0.98, 95% CI = 0.98-0.99, P <
0.001), positive coping styles (OR = 0.97, 95% CI = 0.94-0.99, P = 0.001), and
negative coping styles (OR = 1.03, 95% CI = 1.02-1.05, P < 0.001). CONCLUSION:
Our studies detected the decreased prevalence of child neglect across the three
assessments. Additionally, some sociodemographic, psychosocial and family risk
factors of child neglect were identified, which will be helpful for child neglect
prevention strategies development and implementation in China.
PMID- 29346070
TI - Key pharmacovigilance stakeholders' experiences of direct patient reporting of
adverse drug reactions and their prospects of future development in the European
Union.
AB - OBJECTIVES: In the European Union (EU), legislation allows patients to directly
report adverse drug reactions (ADRs) to competent authorities. Five years after
its implementation, patient reporting is not equal in all countries. This study
aimed to explore key stakeholders' perceptions of patient reporting in four EU
countries. STUDY DESIGN: Qualitative study design. METHODS: Twelve
representatives from national pharmacovigilance centres and/or authorities as
well as national pharmaceutical industry bodies in four EU countries participated
in the study. Supranational organizations were also included. Data collection was
via face-semi-structured interviews. Inductive content analysis was performed
thereafter, applying principles of risk management as a theoretical framework.
RESULTS: Four themes (attitudes and beliefs, system maturation factors,
regulatory improvements, and cultural shifts) emerged, conceptually
interconnected. Participants from countries introducing patient reporting
recently expressed a negative attitude. Participants highlighted the need for
additional resources, both human and financial, to address patient reporting and
associated advantages. CONCLUSIONS: The findings identified perceived barriers
and facilitators of patient reporting. The involvement of patients, use of
information, and dissemination of patient reporting are far from optimal. A
better integration of the work by EU regulatory authorities is recommended.
PMID- 29346071
TI - Identification of potential inhibitors against nuclear Dam1 complex subunit Ask1
of Candida albicans using virtual screening and MD simulations.
AB - Identification of hit compounds against specific target form the starting point
for a drug discovery program. A consistent decline of new chemical entities
(NCEs) in recent years prompted a challenge to explore newer approaches to
discover potential hit compounds that in turn can be converted into leads, and
ultimately drug with desired therapeutic efficacy. The vast amount of omics and
activity data available in public databases offers an opportunity to identify
novel targets and their potential inhibitors. State of the art in silico methods
viz., clustering of compounds, virtual screening, molecular docking, MD
simulations and MMPBSA calculations were employed in a pipeline to identify
potential 'hits' against those targets as well whose structures, as of now, could
only predict through threading approaches. In the present work, we have started
from scratch, amino acid sequence of target and compounds retrieved from PubChem
compound database, modeled it in such a way that led to the identification of
possible inhibitors of Dam1 complex subunit Ask1 of Candida albicans. We also
propose a ligand based binding site determination approach. We have identified
potential inhibitors of Ask1 subunit of a Dam1 complex of C. albicans, which is
required to prevent precocious spindle elongation in pre-mitotic phases. The
proposed scheme may aid to find virtually potential inhibitors of other unique
targets against candida.
PMID- 29346072
TI - Synthesis, biological evaluation and molecular docking studies of novel
benzimidazole derivatives.
AB - A novel series of N-substituted-benzimidazolyl linked para substituted
benzylidene based molecules containing three pharmacologically potent hydrogen
bonding parts namely; 2,4-thiazolidinedione (TZD: a 2,4-dicarbonyl), diethyl
malonate (DEM: a 1,3-diester and an isooxazolidinedione analog) and methyl
acetoacetate (MAA: a beta-ketoester) (6a-11b) were synthesized and evaluated for
in vitro alpha-glucosidase inhibition. The structure of the novel synthesized
compounds was confirmed through the spectral studies (LC-MS, 1H NMR, 13C NMR, FT
IR). Comparative evaluation of these compounds revealed that the compound 9b
showed maximum inhibitory potential against alpha-amylase and alpha-glucosidase
giving an IC50 value of 0.54 +/- 0.01 MUM. Furthermore, binding affinities in
terms of G score values and hydrogen bond interactions between all the
synthesized compounds and the AA residues in the active site of the protein (PDB
code: 3TOP) to that of Acarbose (standard drug) were explored with the help of
molecular docking studies. Compound 9b was considered as promising candidate of
this series.
PMID- 29346073
TI - Extensive conservation of prokaryotic ribosomal binding sites in known and novel
picobirnaviruses.
AB - Currently, the Leviviridae and Cystoviridae are the only two recognized families
of prokaryotic RNA viruses. Picobirnaviruses, which are bisegmented double
stranded RNA viruses commonly found in animal stool samples, are currently
thought to be animal viruses, but have not been propagated in cell culture or in
an animal model. We hypothesize that picobirnaviruses are prokaryotic RNA
viruses. We identified and analyzed the genomes of 38 novel picobirnaviruses and
determined that a classical bacterial sequence motif, the ribosomal binding site
(RBS), is present in the 5' untranslated regions (5' UTRs) of all of the novel as
well as all previously published picobirnavirus sequences. Among all viruses,
enrichment of the RBS motif is only observed in viral families that infect
prokaryotes and not in eukaryotic infecting viral families. These results will
enable future studies to more accurately understand the biology of
picobirnaviruses.
PMID- 29346074
TI - A partial deletion within foot-and-mouth disease virus non-structural protein 3A
causes clinical attenuation in cattle but does not prevent subclinical infection.
AB - Deletions within the 3A coding region of foot-and-mouth disease virus (FMDV) are
associated with decreased virulence in cattle; however, the mechanisms are
unknown. We compared experimental infection of cattle with virulent FMDV O1Campos
(O1Ca) and a mutant derivative (O1Ca?3A) lacking residues 87-106 of 3A.
Unexpectedly, primary infection of the nasopharyngeal mucosa was similar for both
viruses. However, while O1Ca caused viremia and fulminant clinical disease,
O1Ca?3A infection was subclinical and aviremic. There were no differences in
expression of anti-viral cytokines in nasopharyngeal tissues between the groups,
suggesting attenuation by O1Ca?3A was a consequence of reduced replication
efficiency in bovine cells, rather than a difference in the host response. These
results demonstrated that although deletion in 3A of FMDV confers a clinically
attenuated phenotype in cattle, the deletion does not prevent subclinical
infection. These findings have implications for field scenarios involving
outbreaks with apparently host-limited strains of FMDV.
PMID- 29346076
TI - Ultrasensitive electrochemical immuno-sensing platform based on gold
nanoparticles triggering chlorpyrifos detection in fruits and vegetables.
AB - Chlorpyrifos (chl) is an organophosphate pesticide extensively used in
agriculture and highly toxic for human health. Fluorine doped tin-oxide (FTO)
based electrochemical nanosensor was developed for chlorpyrifos detection with
gold nanoparticles (AuNPs) and anti-chlorpyrifos antibodies (chl-Ab). AuNPs
provides high electrical conductivity and specific resistivity, thus increases
the sensitivity of immunoassay. High electrical conductivity of AuNPs reveals
that it promotes the redox reaction for better cyclic voltammetry. Based on the
intrinsic conductive properties of FTO-AuNPs complex, chl-Ab was immobilized onto
AuNPs surface. Under optimized conditions, the proposed FTO based nanosensor
exhibited high sensitivity and stable response for the detection of chlorpyrifos,
ranging from 1fM to 1uM with limit of detection (LOD) up to 10fM. The FTO-AuNPs
sensor was successfully employed for the detection of chlorpyrifos in standard as
well in real samples up to 10nM for apple and cabbage, 50nM for pomegranate. The
proposed FTO-AuNPs nanosensor can be used as a quantitative tool for rapid, on
site detection of chlorpyrifos traces in real samples when miniaturized due to
its excellent stability, sensitivity, and simplicity.
PMID- 29346075
TI - Human Papillomavirus E6 interaction with cellular PDZ domain proteins modulates
YAP nuclear localization.
AB - HPV E6 oncoproteins associate with cellular PDZ proteins. In addition to
previously identified cellular PDZ proteins, we found association of the HPV16 E6
PBM with the Dystrophin Glycoprotein Complex, LRCC1, and SLC9A3R2. HPV18 E6 had
additional associations when lysates from adenomatous cell lines were used
including LRPPRC, RLGAPB, EIF3A, SMC2 and 3, AMOT, AMOTL1, and ARHGEF1; some of
these cellular PDZ proteins are implicated in the regulation of the YAP1
transcriptional co-activator. In keratinocytes, nuclear translocation of YAP1 was
promoted by the complete HPV-16 genome, or by expression of the individual E6 or
E7 oncoproteins; the activity of E6 required an intact PBM at the carboxy
terminus. This work demonstrates that E6 association with cellular PDZ proteins
promotes the nuclear localization of YAP1. The ability of E6 to promote the
nuclear transport of YAP1 thus identifies an E6 activity that could contribute to
the transformation of cells by E6.
PMID- 29346077
TI - Three-dimensional graphene biointerface with extremely high sensitivity to single
cancer cell monitoring.
AB - We developed a three-dimensional biointerface of graphene-based electrical
impedance sensor for metastatic cancer diagnosis at single-cell resolution.
Compared with traditional impedance sensor with two-dimensional interface, the
graphene biointerface mimiced the topography and somatotype features of cancer
cells, achieving more comprehensive and thorough single cell signals in the three
dimensional space. At the nodes of physiological behavior change of single cell,
namely cell capture, adhesion, migration and proliferation, the collected
electrical signals from graphene biointerface were about two times stronger than
those from the two-dimensional gold interface due to the substantial increase in
contact area and significant improvement of topographical interaction between
cells and graphene electrode. Simultaneous CCD recording and electrical signal
extraction from the entrapped single cell on the graphene biointerface enabled to
investigate multidimensional cell-electrode interactions and predict cancerous
stage and pathology.
PMID- 29346078
TI - Long-term high air pollution exposure induced metabolic adaptations in traffic
policemen.
AB - OBJECTIVE: To assess the adverse physiological changes induced by long-term
exposure to PM2.5. METHODS: Totally 183 traffic policemen and 88 office policemen
as the control group, were enrolled in this study. The concentrations of PM2.5 in
both the working places of traffic and office policemen were obtained. Detailed
personal questionnaires and conventional laboratory tests including hematology,
fasting blood glucose, blood lipids, liver, kidney, immunity and tumor-related
markers were conducted on all participants of this study. RESULTS: A dose
response relationship between the FBG, HDL-c and CEA values and the PM2.5
exposure duration was observed. Multivariate analysis confirmed that one hour on
duty outdoor per day for one year was associated with an increase in FBG of
0.005% (95% CI: 0.0004% to 0.009%), CEA of 0.012% (95% CI: 0.006% to 0.017%), and
a decrease in HDL-C of 0.001% (95% CI: 0.00034% to 0.002%). CONCLUSION: Long-term
high air pollution exposure may lead to metabolism adaptation and it is likely
involved in the development of cardiovascular disease and diabetes mellitus.
PMID- 29346079
TI - A recognition mechanism study: Luminescent metal-organic framework for the
detection of nitro-explosives.
AB - This article presents a recognition mechanism for nitro-explosives by the
luminescent metal-organic framework 1 (LMOF-1) with the aid of density functional
theory (DFT) and time-dependent density functional theory (TDDFT). The behavior
of hydrogen bonding between the LMOF-1 and nitro-explosives in the S1 state is
closely associated with the fluorescence properties of the LMOF-1. In our
research, we calculated the geometric configuration, 1H NMR and IR spectra of the
Complex 2 formed by LMOF-1 and nitrobenzene in the S0 and S1 states. The results
showed that the hydrogen bond in the S1 state was increased, which was
unfavorable for the luminescence of LMOF-1. Furthermore, the fluorescence rate of
LMOF-1 decreased after encapsulating nitrobenzene into it. These calculated
results collectively suggest that LMOF-1 is a potential fluorescence sensor for
the detection of nitro-explosives. This research was aiming to provide a better
understanding of the recognition mechanism by LMOFs for nitro-explosives.
PMID- 29346080
TI - New insight into the action of tryptanthrins against Plasmodium falciparum:
Pharmacophore identification via a novel submolecular QSAR descriptor.
AB - A new submolecular quantitative structure activity relationship (QSAR) descriptor
was applied toward elucidating the anti-malarial pharmacophore of tryptanthrins,
a class of compounds known for their anti-parasitic activities. The new
descriptor is based on experimental and computational measurements of the
tunneling barriers of individual lobes of the molecular orbitals. Lobe-by-lobe
QSAR correlation plots revealed a single lobe of the LUMO to be strongly
associated with tryptanthrin's anti-malarial activity. The correlation also
showed a threshold behavior wherein barriers below a particular value show low
IC50 values. Above the threshold, the correlation of IC50 vs the logarithm of the
barrier is linear with R2 = 0.999. This barrier threshold may be applied as a
design criterion for future tryptanthrin-based anti-malarial lead optimization.
The new descriptor may be broadly applicable toward other molecular systems of
interest, such as catalysts, pesticides, and herbicides. The authors have named
the new descriptor: submolecular tunneling analysis of barriers (STAB).
PMID- 29346081
TI - Reported balance confidence and movement reinvestment of younger knee replacement
patients are more like younger healthy individuals, than older patients.
AB - This study focused on differences between the rapidly growing younger (<65 years
old) and older (>65 years old) total knee replacement (TKR) patients for measures
of balance confidence, movement reinvestment, and functional mobility. Fifty-nine
participants, including twenty-nine primary unilateral TKR patients (six months
post-TKR) formed the four experimental groups: 1) Younger TKR Patient (YP), 2)
Younger Control (YC), 3) Older TKR Patient (OP), and 4) Older Control (OC). The
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the
Oxford Knee Score (OKS), Activities-specific Balance Confidence scale (ABC), the
Movement-Specific Reinvestment Scale (MSRS), and the Timed Up and Go (TUG) test
were measured. The YP group reported a significantly lower WOMAC score (p <
0.001), and higher perceived knee joint function (p = 0.001), compared to the OP
group. The YP group also reported significantly higher balance confidence (p <
0.001) and less movement reinvestment (p = 0.001) than the OP group. TUG
durations revealed that the YP group had significantly higher functional mobility
compared to the OP group (p = 0.001). The YP group did not differ from the YC
group across any of these measures (p > 0.05). These results identify a clear
distinction between younger and older TKR patients for fall risk and TKR outcome,
which argues that age should be a factor clinicians take into account when
addressing the management and care of individuals recovering from TKR.
PMID- 29346082
TI - Distal upper limb kinematics during functional everyday tasks.
AB - Quantitative characterisation of upper limb motion allows the evaluation of the
effect of pathology on functional task performance, potentially directing
rehabilitation strategies. Movement patterns of the distal upper limb in healthy
adults during functional tasks have not been extensively characterised. During
five loaded functional tasks (drinking from a glass, pouring from a kettle,
turning a handle, lifting a bag to a shelf, turning a key) the movement patterns
were characterised using three-dimensional motion analysis with a minimal marker
set in 16 healthy adults (10 M,6F, 27 (IQR:25-43)years). Joint angles reported
include flexion/extension at the elbow and wrist, forearm supination/pronation
and digits 2-5 metacarpophalangeal (MCP) joint flexion/extension. Additionally
for the thumb the angle between the metacarpal of the thumb and the 2nd digit
(Thumb base), the thumb MCP (Thumb MCP) and interphalangeal (Thumb IP) joint
angles are presented. Durations of activities performed at self-selected
comfortable speeds (3.36 (IQR:3.07,3.66)s turning a key to 6.20 (IQR:5.44,6.38)s
drinking from a glass) are reported. The maximum joint angles used (median of
participants' maxima) were 141 degrees of elbow flexion, 116 degrees forearm
supination, 36 degrees wrist extension, 56 degrees Thumb base, 14 degrees
Thumb MCP flexion, 18 degrees Thumb IP flexion, 85 degrees MCP2-5 flexion. The
tasks of drinking from a glass, lifting a bag to a shelf and turning a key
appeared to have the least variation in performance, suggesting that these
activities are better suited to be selected as standardized tasks for assessing
the impact of pathology on movement than pouring from a kettle and turning a
handle.
PMID- 29346083
TI - Testing the cognitive catalyst model of rumination with explicit and implicit
cognitive content.
AB - BACKGROUND AND OBJECTIVES: The cognitive catalyst model posits that rumination
and negative cognitive content, such as negative schema, interact to predict
depressive affect. Past research has found support for this model using explicit
measures of negative cognitive content such as self-report measures of trait self
esteem and dysfunctional attitudes. The present study tested whether these
findings would extend to implicit measures of negative cognitive content such as
implicit self-esteem, and whether effects would depend on initial mood state and
history of depression. METHOD: Sixty-one undergraduate students selected on the
basis of depression history (27 previously depressed; 34 never depressed)
completed explicit and implicit measures of negative cognitive content prior to
random assignment to a rumination induction followed by a distraction induction
or vice versa. Dysphoric affect was measured both before and after these
inductions. RESULTS: Analyses revealed that explicit measures, but not implicit
measures, interacted with rumination to predict change in dysphoric affect, and
these interactions were further moderated by baseline levels of dysphoria.
LIMITATIONS: Limitations include the small nonclinical sample and use of a self
report measure of depression history. CONCLUSIONS: These findings suggest that
rumination amplifies the association between explicit negative cognitive content
and depressive affect primarily among people who are already experiencing sad
mood.
PMID- 29346084
TI - Effects of the road environment on the development of driver sleepiness in young
male drivers.
AB - Latent driver sleepiness may in some cases be masked by for example social
interaction, stress and physical activity. This short-term modulation of
sleepiness may also result from environmental factors, such as when driving in
stimulating environments. The aim of this study is to compare two road
environments and investigate how they affect driver sleepiness. Thirty young male
drivers participated in a driving simulator experiment where they drove two
scenarios: a rural environment with winding roads and low traffic density, and a
suburban road with higher traffic density and a more built-up roadside
environment. The driving task was essentially the same in both scenarios, i.e. to
stay on the road, without much interaction with other road users. A 2 * 2 design,
with the conditions rural versus suburban, and daytime (full sleep) versus night
time (sleep deprived), was used. The results show that there were only minor
effects of the road environment on subjective and physiological indicators of
sleepiness. In contrast, there was an increase in subjective sleepiness, longer
blink durations and increased EEG alpha content, both due to time on task and to
night-time driving. The two road environments differed both in terms of the
demand on driver action and of visual load, and the results indicate that action
demand is the more important of the two factors. The notion that driver fatigue
should be countered in a more stimulating visual environment such as in the city
is thus more likely due to increased task demand rather than to a richer visual
scenery. This should be investigated in further studies.
PMID- 29346085
TI - Performance of the BioPlex 2200 HIV Ag-Ab assay for identifying acute HIV
infection.
AB - BACKGROUND: Assays that detect HIV antigen (Ag) and antibody (Ab) can be used to
screen for HIV infection. OBJECTIVES: To compare the performance of the BioPlex
2200 HIV Ag-Ab assay and two other Ag/Ab combination assays for detection of
acute HIV infection. STUDY DESIGN: Samples were obtained from 24 individuals (18
from the US, 6 from South Africa); these individuals were classified as having
acute infection based on the following criteria: positive qualitative RNA assay;
two negative rapid tests; negative discriminatory test. The samples were tested
with the BioPlex assay, the ARCHITECT HIV Ag/Ab Combo test, the Bio-Rad GS HIV
Combo Ag-Ab EIA test, and a viral load assay. RESULTS: Twelve (50.0%) of 24
samples had RNA detected only ( > 40 to 13,476 copies/mL). Ten (43.5%) samples
had reactive results with all three Ag/Ab assays, one sample was reactive with
the ARCHITECT and Bio-Rad assays, and one sample was reactive with the Bio-Rad
and BioPlex assays. The 11 samples that were reactive with the BioPlex assay had
viral loads from 83,010 to >750,000 copies/mL; 9/11 samples were classified as Ag
positive/Ab negative by the BioPlex assay. CONCLUSIONS: Detection of acute HIV
infection was similar for the BioPlex assay and two other Ag/Ab assays. All three
tests were less sensitive than a qualitative RNA assay and only detected HIV Ag
when the viral load was high. The BioPlex assay detected acute infection in about
half of the cases, and identified most of those infections as Ag positive/Ab
negative.
PMID- 29346086
TI - The dynamics of a serum steroid profile after stimulation with intravenous ACTH.
AB - BACKGROUND: Stimulation with intravenous adrenocorticotropic hormone (ACTH) is a
widely used diagnostic procedure to characterize the adrenocortical function.
Currently, the response of serum cortisol, mainly quantified by immunoassays, is
the only established read-out of this test. By using liquid chromatography
coupled with mass spectrometry (LC-MS/MS) simultaneous determination of several
steroids that respond to ACTH stimulation is now possible. The aim of this study
was to further characterize the typical effect of exogenous ACTH (250 mg) on a LC
MS/MS-serum steroid profile. METHODS: A set of 36 paired samples (pre-/post-IV
ACTH) was investigated (age range 22-58, 26 female and 10 male individuals).
Serum steroid profiling was performed using a LC-MS/MS method covering cortisol,
cortisone, corticosterone, 11-deoxycortisol, 17-OH-progesterone and 11
deoxycorticosterone. RESULTS: The concentrations of all measured steroids
increased after stimulation with ACTH, except for cortisone. Serum
corticosterone, 11-deoxycorticosterone and 11-deoxycortisol showed markedly more
pronounced relative increases compared to cortisol. The strongest response was
observed for corticosterone (15-fold median relative increase, compared to 1.4
fold median increase of cortisol). CONCLUSION: Serum steroid profiling using LC
MS/MS after stimulation with IV ACTH demonstrates highly dynamic response
patterns. Further studies should address in particular serum corticosterone as a
potential novel marker of biochemical stress response.
PMID- 29346087
TI - A "not-for-profit" regulatory model for legal recreational cannabis: Insights
from the regulation of gaming machine gambling in New Zealand.
AB - A dozen or more regulatory frameworks have been proposed for legal cannabis but
many of the "not-for-profit" options have yet to be developed in any detail,
reducing the likelihood they will be seriously considered by policy makers. New
Zealand's innovative "not-for-profit" regulatory regime for gaming machine
gambling (i.e. "slot machines") has reversed the previous increase in gambling
expenditure, empowered local councils to cap the number of gambling venues, and
is unique in requiring the societies operating gaming machines to distribution
40% of the gross expenditure from machines (i.e. $NZ 262 million in 2015) to
community purposes (e.g. sports). However, the regime has been criticised for not
addressing the concentration of gaming outlets in poorer communities, and not
requiring grants to be allocated in the disadvantaged communities where outlets
are located. There have also been cases of gaming societies providing community
grants in exchange for direct or indirect benefits. In this paper we adapt this
regulatory approach to a legal cannabis market. Under the proposed regime,
licensed "not-for-profit" cannabis societies will be required to distribute 20%
of cannabis sales to drug treatment and 20% to community purposes, including drug
prevention. Grants must be allocated in the regions where cannabis sales are made
and grant committees must be independent from cannabis societies. A 20% levy will
be used to cover the wider health costs of cannabis use. A further 10% levy will
be used to fund the regulator and evaluate the new regime. Local councils will
have the power to decide how many, and where, cannabis retail outlets are
located. Other important elements include a minimum price for cannabis, effective
taxation of cannabis products, regulating CBD in cannabis products, higher
taxation of traditional smoking products, advertising restricted to place-of
sale, no internet sales, and restrictions on industry involvement in regulation
making and research.
PMID- 29346088
TI - Intense olfactory stimulation blocks seizures in an experimental model of
epilepsy.
AB - There are reports of patients whose epileptic seizures are prevented by means of
olfactory stimulation. Similar findings were described in animal models of
epilepsy, such as the electrical kindling of amygdala, where olfactory
stimulation with toluene (TOL) suppressed seizures in most rats, even when the
stimuli were 20% above the threshold to evoke seizures in already kindled
animals. The Wistar Audiogenic Rat (WAR) strain is a model of tonic-clonic
seizures induced by acute acoustic stimulation, although it also expresses limbic
seizures when repeated acoustic stimulation occurs - a process known as
audiogenic kindling (AK). The aim of this study was to evaluate whether or not
the olfactory stimulation with TOL would interfere on the behavioral expression
of brainstem (acute) and limbic (chronic) seizures in the WAR strain. For this,
animals were exposed to TOL or saline (SAL) and subsequently exposed to acoustic
stimulation in two conditions that generated: I) acute audiogenic seizures (only
one acoustic stimulus, without previous seizure experience before of the odor
test) and II) after AK (20 acoustic stimuli [2 daily] before of the protocol
test). We observed a decrease in the seizure severity index of animals exposed
only to TOL in both conditions, with TOL presented 20s before the acoustic
stimulation in both protocols. These findings were confirmed by behavioral
sequential analysis (neuroethology), which clearly indicated an exacerbation of
clusters of specific behaviors such as exploration and grooming (self-cleaning),
as well as significant decrease in the expression of brainstem and limbic
seizures in response to TOL. Thus, these data demonstrate that TOL, a strong
olfactory stimulus, has anticonvulsant properties, detected by the decrease of
acute and AK seizures in WARs.
PMID- 29346089
TI - Genererating a core cluster of Fasciola hepatica virulence and immunomodulation
related genes using a comparative in silico approach.
AB - A total of 71 virulence and immunomodulation-related transcripts (VIRs) of
Fasciola hepatica have been previously proposed (Hacariz et al., 2015). In an
attempt to further refine this cohort, an in silico meta analysis approach was
carried out using publicly available sequence data of related liver flukes,
Clonorchis sinensis and Opisthorchis viverrini. Data of both liver flukes were
investigated in terms of sequential homology with data of non-parasitic
organisms, pathogens and VIRs of F. hepatica, directional selection (Ka/Ks), and
cytokine signaling relation (protein motif based). Some VIRs of F. hepatica
[showing homology with immune receptors (for toll/interleukin-1, TGF-beta or TNF
alpha), TGF-beta, TNF-alpha, CD147, or relation with suppressors of cytokine
signaling/IKBKE 1 or stimulation of TGF-beta (through thrombospondin similarity)]
were found to be orthologous with those of both C. sinensis and O. viverrini. The
in silico analysis indicates that on the basis of genetic commonality, a total of
30 VIRs of F. hepatica are highlighted as of foremost importance in the parasite
evasion strategy, through controlling of host immune system. Findings in this
study could be important to further enhance our understanding of the parasitic
mechanisms and develop effective control strategies against F. hepatica and other
related parasites.
PMID- 29346090
TI - Fast 2D Complex Gabor Filter With Kernel Decomposition.
AB - 2D complex Gabor filtering has found numerous applications in the fields of
computer vision and image processing. Especially, in some applications, it is
often needed to compute 2D complex Gabor filter bank consisting of filtering
outputs at multiple orientations and frequencies. Although several approaches for
fast Gabor filtering have been proposed, they focus primarily on reducing the
runtime for performing filtering once at specific orientation and frequency. To
obtain the Gabor filter bank, the existing methods are repeatedly applied with
respect to multiple orientations and frequencies. In this paper, we propose a
novel approach that efficiently computes the 2D complex Gabor filter bank by
reducing the computational redundancy that arises when performing filtering at
multiple orientations and frequencies. The proposed method first decomposes the
Gabor kernel to allow a fast convolution with the Gaussian kernel in a separable
manner. This enables reducing the runtime of the Gabor filter bank by reusing
intermediate results computed at a specific orientation. By extending this idea,
we also propose a fast approach for 2D localized sliding discrete Fourier
transform that uses the Gaussian kernel in order to lend spatial localization
ability as in the Gabor filter. Experimental results demonstrate that the
proposed method runs faster than the state-of-the-art methods, while maintaining
similar filtering quality.
PMID- 29346091
TI - Plenoptic Image Motion Deblurring.
AB - We propose a method to remove motion blur in a single light field captured with a
moving plenoptic camera. Since motion is unknown, we resort to a blind
deconvolution formulation, where one aims to identify both the blur point spread
function and the latent sharp image. Even in the absence of motion, light field
images captured by a plenoptic camera are affected by a non-trivial combination
of both aliasing and defocus, which depends on the 3D geometry of the scene.
Therefore, motion deblurring algorithms designed for standard cameras are not
directly applicable. Moreover, many state of the art blind deconvolution
algorithms are based on iterative schemes, where blurry images are synthesized
through the imaging model. However, current imaging models for plenoptic images
are impractical due to their high dimensionality. We observe that plenoptic
cameras introduce periodic patterns that can be exploited to obtain highly
parallelizable numerical schemes to synthesize images. These schemes allow
extremely efficient GPU implementations that enable the use of iterative methods.
We can then cast blind deconvolution of a blurry light field image as a
regularized energy minimization to recover a sharp high-resolution scene texture
and the camera motion. Furthermore, the proposed formulation can handle non
uniform motion blur due to camera shake as demonstrated on both synthetic and
real light field data.
PMID- 29346092
TI - Hierarchical and Spatio-Temporal Sparse Representation for Human Action
Recognition.
AB - In this paper, we present a novel two-layer video representation for human action
recognition employing hierarchical group sparse encoding technique and spatio
temporal structure. In the first layer, a new sparse encoding method named
locally consistent group sparse coding (LCGSC) is proposed to make full use of
motion and appearance information of local features. LCGSC method not only
encodes global layouts of features within the same video-level groups, but also
captures local correlations between them, which obtains expressive sparse
representations of video sequences. Meanwhile, two kinds of efficient location
estimation models, namely an absolute location model and a relative location
model, are developed to incorporate spatio-temporal structure into LCGSC
representations. In the second layer, action-level group is established, where a
hierarchical LCGSC encoding scheme is applied to describe videos at different
levels of abstractions. On the one hand, the new layer captures higher order
dependency between video sequences; on the other hand, it takes label information
into consideration to improve discrimination of videos' representations. The
superiorities of our hierarchical framework are demonstrated on several
challenging datasets.
PMID- 29346093
TI - Multipolarization Through-Wall Radar Imaging Using Low-Rank and Jointly-Sparse
Representations.
AB - Compressed sensing techniques have been applied to through-the-wall radar imaging
(TWRI) and multipolarization TWRI for fast data acquisition and enhanced target
localization. The studies so far in this area have either assumed effective wall
clutter removal prior to image formation or performed signal estimation, wall
clutter mitigation, and image formation independently. This paper proposes a low
rank and sparse imaging model for jointly addressing the problem of wall clutter
mitigation and image formation in multichannel TWRI. The proposed model exploits
two important structures of through-wall radar signals: low-rank structure of the
wall reflections and jointly-sparse structure among the different polarization
images. The task of removing wall clutter and reconstructing multichannel images
of the same scene behind-the-wall is formulated as a regularized least squares
problem, where low-rank regularization is enforced for the wall components, and
joint-sparsity penalty is imposed on channel images. To solve the optimization
problem, an iterative algorithm based on the proximal gradient technique is
introduced, which simultaneously estimates the wall interferences and yields
multichannel images of the indoor targets. Experiments on real and simulated
radar data are conducted under full measurements and compressive sensing
scenarios. The results show that the proposed model is very effective at removing
unwanted wall clutter and enhancing the stationary targets, even under
considerable reduction in measurements.
PMID- 29346094
TI - Reweighted Low-Rank Matrix Analysis With Structural Smoothness for Image
Denoising.
AB - In this paper, we develop a new low-rank matrix recovery algorithm for image
denoising. We incorporate the total variation (TV) norm and the pixel range
constraint into the existing reweighted low-rank matrix analysis to achieve
structural smoothness and to significantly improve quality in the recovered
image. Our proposed mathematical formulation of the low-rank matrix recovery
problem combines the nuclear norm, TV norm, and norm, thereby allowing us to
exploit the low-rank property of natural images, enhance the structural
smoothness, and detect and remove large sparse noise. Using the iterative
alternating direction and fast gradient projection methods, we develop an
algorithm to solve the proposed challenging non-convex optimization problem. We
conduct extensive performance evaluations on single-image denoising, hyper
spectral image denoising, and video background modeling from corrupted images.
Our experimental results demonstrate that the proposed method outperforms the
state-of-the-art low-rank matrix recovery methods, particularly for large random
noise. For example, when the density of random sparse noise is 30%, for single
image denoising, our proposed method is able to improve the quality of the
restored image by up to 4.21 dB over existing methods.
PMID- 29346095
TI - Feature Map Quality Score Estimation Through Regression.
AB - Understanding the visual quality of a feature map plays a significant role in
many active vision applications. Previous works mostly rely on object-level
features, such as compactness, to estimate the quality score of a feature map.
However, the compactness is leveraged on feature maps produced by salient object
detection techniques where the maps tend to be compact. As a result, the
compactness feature fails when the feature maps are blurry (e.g., fixation maps).
In this paper, we regard the process of estimating the quality score of feature
maps, specifically fixation maps, as a regression problem. After extracting
several local, global, geometric, and positional characteristic features from a
feature map, a model is learned using a random forest regressor to estimate the
quality score of any unseen feature map. Our model is specifically tailored to
estimate the quality of three types of maps: bottom-up, target, and contextual
feature maps. These maps are produced for a large benchmark fixation data set of
more than 900 challenging outdoor images. We demonstrate that our approach
provides an accurate estimate of the quality of the abovementioned feature maps
compared to the groundtruth data. In addition, we show that our proposed approach
is useful in feature map integration for predicting human fixation. Instead of
naively integrating all three feature maps when predicting human fixation, our
proposed approach dynamically selects the best feature map with the highest
estimated quality score on an individual image basis, thereby improving the
fixation prediction accuracy.
PMID- 29346096
TI - Iterative Graph Seeking for Object Tracking.
AB - To effectively solve the challenges in object tracking, such as large deformation
and severe occlusion, many existing methods use graph-based models to capture
target part relations, and adopt a sequential scheme of target part selection,
part matching, and state estimation. However, such methods have two major
drawbacks: 1) inaccurate part selection leads to performance deterioration of
part matching and state estimation and 2) there are insufficient effective global
constraints for local part selection and matching. In this paper, we propose a
new object tracking method based on iterative graph seeking, which integrate
target part selection, part matching, and state estimation using a unified energy
minimization framework. Our method also incorporates structural information in
local parts variations using the global constraint. We devise an alternative
iteration scheme to minimize the energy function for searching the most plausible
target geometric graph. Experimental results on several challenging benchmarks
(i.e., VOT2015, OTB2013, and OTB2015) demonstrate improved performance and
robustness in comparison with existing algorithms.
PMID- 29346097
TI - Change Detection in Heterogenous Remote Sensing Images via Homogeneous Pixel
Transformation.
AB - The change detection in heterogeneous remote sensing images remains an important
and open problem for damage assessment. We propose a new change detection method
for heterogeneous images (i.e., SAR and optical images) based on homogeneous
pixel transformation (HPT). HPT transfers one image from its original feature
space (e.g., gray space) to another space (e.g., spectral space) in pixel-level
to make the pre-event and post-event images represented in a common space for the
convenience of change detection. HPT consists of two operations, i.e., the
forward transformation and the backward transformation. In forward
transformation, for each pixel of pre-event image in the first feature space, we
will estimate its mapping pixel in the second space corresponding to post-event
image based on the known unchanged pixels. A multi-value estimation method with
noise tolerance is introduced to determine the mapping pixel using -nearest
neighbors technique. Once the mapping pixels of pre-event image are available,
the difference values between the mapping image and the post-event image can be
directly calculated. After that, we will similarly do the backward transformation
to associate the post-event image with the first space, and one more difference
value for each pixel will be obtained. Then, the two difference values are
combined to improve the robustness of detection with respect to the noise and
heterogeneousness (modality difference) of images. Fuzzy-c means clustering
algorithm is employed to divide the integrated difference values into two
clusters: changed pixels and unchanged pixels. This detection results may contain
some noisy regions (i.e., small error detections), and we develop a spatial
neighbor-based noise filter to further reduce the false alarms and missing
detections using belief functions theory. The experiments for change detection
with real images (e.g., SPOT, ERS, and NDVI) during a flood in U.K. are given to
validate the effectiveness of the proposed method.
PMID- 29346098
TI - Region-Based Prediction for Image Compression in the Cloud.
AB - Thanks to the increasing number of images stored in the cloud, external image
similarities can be leveraged to efficiently compress images by exploiting inter
images correlations. In this paper, we propose a novel image prediction scheme
for cloud storage. Unlike current state-of-the-art methods, we use a semi-local
approach to exploit inter-image correlation. The reference image is first
segmented into multiple planar regions determined from matched local features and
super-pixels. The geometric and photometric disparities between the matched
regions of the reference image and the current image are then compensated.
Finally, multiple references are generated from the estimated compensation models
and organized in a pseudo-sequence to differentially encode the input image using
classical video coding tools. Experimental results demonstrate that the proposed
approach yields significant rate-distortion performance improvements compared
with the current image inter-coding solutions such as high efficiency video
coding.
PMID- 29346099
TI - Cell Membrane Tracking in Living Brain Tissue Using Differential Interference
Contrast Microscopy.
AB - Differential interference contrast (DIC) microscopy is widely used for observing
unstained biological samples that are otherwise optically transparent. Combining
this optical technique with machine vision could enable the automation of many
life science experiments; however, identifying relevant features under DIC is
challenging. In particular, precise tracking of cell boundaries in a thick ( )
slice of tissue has not previously been accomplished. We present a novel
deconvolution algorithm that achieves the state-of-the-art performance at
identifying and tracking these membrane locations. Our proposed algorithm is
formulated as a regularized least squares optimization that incorporates a
filtering mechanism to handle organic tissue interference and a robust edge
sparsity regularizer that integrates dynamic edge tracking capabilities. As a
secondary contribution, this paper also describes new community infrastructure in
the form of a MATLAB toolbox for accurately simulating DIC microscopy images of
in vitro brain slices. Building on existing DIC optics modeling, our simulation
framework additionally contributes an accurate representation of interference
from organic tissue, neuronal cell-shapes, and tissue motion due to the action of
the pipette. This simulator allows us to better understand the image statistics
(to improve algorithms), as well as quantitatively test cell segmentation and
tracking algorithms in scenarios, where ground truth data is fully known.
PMID- 29346100
TI - Improving Color Constancy in an Ambient Light Environment Using the Phong
Reflection Model.
AB - We present a physics-based illumination estimation approach explicitly designed
to handle natural images under ambient light. Existing physics-based color
constancy methods are theoretically perfect but do not handle real-world images
well because the majority of these methods assume a single illuminant. Therefore,
specular pixels selected using existing methods produce estimated dichromatic
lines that are thick or curvilinear in the presence of ambient light, thus
generating significant errors. Based on the Phong reflection model, we show that
a group of specular pixels on a uniformly colored object, although they are
subject to intensity thresholding, produce a unique dichromatic line length
depending on the geometry of each image path. Assuming that the longest
dichromatic line is the most desirable when estimating the chromaticity of an
illuminant, ambient-robust specular pixels are also found on the same path on
which the longest dichromatic line segment is generated. Therefore, we propose a
method to find the optimal image path in which the specular pixels produce the
longest dichromatic line. Even though the number of collected specular pixels is
reduced using the proposed method, they are proven to be more accurate when
determining the illuminant chromaticity even in the existing methods. Experiments
with an established benchmark data set and a self-produced image set find that
the proposed method is better able to locate the illuminant chromaticity compared
with the state-of-the-art color constancy methods.
PMID- 29346101
TI - Stacked Denoising Tensor Auto-Encoder for Action Recognition With Spatiotemporal
Corruptions.
AB - Spatially or temporally corrupted action videos are impractical for recognition
via vision or learning models. It usually happens when streaming data are
captured from unintended moving cameras, which bring occlusion or camera
vibration and accordingly result in arbitrary loss of spatiotemporal information.
In reality, it is intractable to deal with both spatial and temporal corruptions
at the same time. In this paper, we propose a coupled stacked denoising tensor
auto-encoder (CSDTAE) model, which approaches this corruption problem in a divide
and-conquer fashion by jointing both the spatial and temporal schemes together.
In particular, each scheme is a SDTAE designed to handle either spatial or
temporal corruption, respectively. SDTAE is composed of several blocks, each of
which is a denoising tensor auto-encoder (DTAE). Therefore, CSDTAE is designed
based on several DTAE building blocks to solve the spatiotemporal corruption
problem simultaneously. In one DTAE, the video features are represented as a high
order tensor to preserve the spatiotemporal structure of data, where the temporal
and spatial information are processed separately in different hidden layers via
tensor unfolding. In summary, DTAE explores the spatial and temporal structure of
the tensor representation, and SDTAE handles different corrupted ratios
progressively to extract more discriminative features. CSDTAE couples the
temporal and spatial corruptions of the same data through a thorough step-by-step
procedure based on canonical correlation analysis, which integrates the two sub
problems into one problem. The key point is solving the spatiotemporal corruption
in one model by considering them as noises in either spatial or temporal
direction. Extensive experiments on three action data sets demonstrate the
effectiveness of our model, especially when large volumes of corruption in the
video.
PMID- 29346102
TI - Impedance Measures During in vitro Cochlear Implantation Predict Array
Positioning.
AB - OBJECTIVE: Improper electrode placement during cochlear implant (CI) insertion
can adversely affect speech perception outcomes. However, the intraoperative
methods to determine positioning are limited. Because measures of electrode
impedance can be made quickly, the goal of this study was to assess the
relationship between CI impedance and proximity to adjacent structures. METHODS:
An Advanced Bionics CI array was inserted into a clear, plastic cochlea one
electrode contact at a time in a saline bath (nine trials). At each insertion
depth, response to biphasic current pulses was used to calculate access
resistance (Ra), polarization resistance (Rp), and polarization capacitance (Cp).
These measures were correlated to actual proximity as assessed by microscopy
using linear regression models. RESULTS: Impedance increased with insertion depth
and proximity to the inner wall. Specifically, Ra increased, Cp decreased, and Rp
slightly increased. Incorporating all impedance measures afforded a prediction
model (r = 0.88) while optimizing for sub-mm positioning afforded a model with
78.3% specificity. CONCLUSION: Impedance in vitro greatly changes with electrode
insertion depth and proximity to adjacent structures in a predicable manner.
SIGNIFICANCE: Assessing proximity of the CI to adjacent structures is a
significant first step in qualifying the electrode-neural interface. This
information should aid in CI fitting, which should help maximize hearing and
speech outcomes with a CI. Additionally, knowledge of the relationship between
impedance and positioning could have utility in other tissue implants in the
brain, retina, or spinal cord.
PMID- 29346103
TI - WaveDec: A Wavelet Approach to Identify Both Shared and Individual Patterns of
Copy-Number Variations.
AB - : Copy-number variations (CNVs) are associated with complex diseases and
particular tumor types. Array-based comparative genomic hybridization (aCGH) is a
common approach for the detection of CNVs. Traditional CNV detection methods for
multiple aCGH samples mainly use batch samples to find common variations, not
accounting for the individual characteristics of each sample. Accurately
differentiating both the commonly shared and the individual CNV patterns is
pivotal to identify cell populations, or to distinguish cell growth (as in
cancer) from invasion of new cells. Our preliminary results have now demonstrated
that both the shared and individual CNV patterns have distinctive characteristics
after wavelet transform. METHODS: To exploit these characteristics, we propose to
formulate a quadratic data-separation problem within the wavelet space to
discriminate the shared and individual CNVs from raw data. We have elaborated a
numerical solution and shown that the solution can be obtained by solving
decoupled subproblems. By this approach, computational costs can be limited,
enabling efficient application in the analysis of large sequencing datasets.
RESULTS: The advantages of our proposed method, called WaveDec, have been
demonstrated by comparison with popular CNV-detection methods using synthetic and
empirical aCGH data. The performance of WaveDec was further validated by
experiments with single-cell-sequencing data. CONCLUSION: WaveDec can
successfully differentiate shared and individual patterns, and performs well even
in data contaminated with high levels of noise. SIGNIFICANCE: Both the shared and
individual patterns can be uniquely characterized as well as effectively
decomposed within the wavelet space.
PMID- 29346104
TI - Characterization and Modeling of Tissue Thermal Conductivity During an
Electrosurgical Joining Process.
AB - Electrosurgical vessel joining is commonly performed in surgical procedures to
maintain hemostasis. This process requires elevated temperature to denature the
tissue and while compression is applied, the tissue can be joined together. The
elevated temperature can cause thermal damages to the surrounding tissues. In
order to minimize these damages, it is critical to understand how the tissue
properties change and how that affects the thermal spread. The purpose of this
study is to investigate the changes of tissue thermal conductivity and how the
changes correlate to thermal dose during the joining process. We propose a hybrid
method combining experimental measurement with inverse heat transfer analysis to
determine thermal conductivity of thin tissue sample. Porcine aorta arterial
tissues were used to investigate tissue thermal conductivity with variable
thermal dose. Different joining times were used to create different amounts of
thermal dose. A 36% decrease in tissue thermal conductivity was found when the
thermal dose reaches the threshold for second-degree burn. When thermal dose is
beyond the threshold of third-degree burn, the tissue thermal conductivity does
not decrease significantly. A regression model was also developed and can be used
to predict tissue thermal conductivity based on the thermal dose.
PMID- 29346106
TI - Spatial Position Measurement System for Surgical Navigation Using 3-D Image
Marker-Based Tracking Tools With Compact Volume.
AB - We develop a spatial position measurement system using three-dimensional (3-D)
image marker-based tracking tools targeted at surgical navigation in minimally
invasive surgery. We generate 3-D image markers with spatial information encoded
to 2-D images, design tracking tools with the 3-D image markers, and analyze the
tracking tools' theoretical spatial errors, which are primarily limited by the
spatial distribution of reconstructed fiducial 3-D markers. A pattern analysis
based positional measurement algorithm is developed to calculate the tool's
spatial information using its spatial configuration. Evaluation experiments were
conducted to demonstrate the accuracy and effectiveness of the proposed system.
Furthermore, surgical navigation feasibility studies were performed. With a
patient-image registration algorithm, a navigation interface that shows
preoperative medical data and intraoperative information about the tool can
intuitively and accurately assist surgeons. The results demonstrate that the
proposed tracking tools, which have compact volume and spatial positional
information, are of potential use in minimally invasive surgery in a limited
space.
PMID- 29346105
TI - Automated Detection of Postictal Generalized EEG Suppression.
AB - Although there is no strict consensus, some studies have reported that Postictal
generalized EEG suppression (PGES) is a potential electroencephalographic (EEG)
biomarker for risk of sudden unexpected death in epilepsy (SUDEP). PGES is an
epoch of EEG inactivity after a seizure, and the detection of PGES in clinical
data is extremely difficult due to artifacts from breathing, movement and muscle
activity that can adversely affect the quality of the recorded EEG data. Even
clinical experts visually interpreting the EEG will have diverse opinions on the
start and end of PGES for a given patient. The development of an automated EEG
suppression detection tool can assist clinical personnel in the review and
annotation of seizure files, and can also provide a standard for quantifying PGES
in large patient cohorts, possibly leading to further clarification of the role
of PGES as a biomarker of SUDEP risk. In this paper, we develop an automated
system that can detect the start and end of PGES using frequency domain features
in combination with boosting classification algorithms. The average power for
different frequency ranges of EEG signals are extracted from the prefiltered
recorded signal using the fast fourier transform and are used as the feature set
for the classification algorithm. The underlying classifiers for the boosting
algorithm are linear classifiers using a logistic regression model. The tool is
developed using 12 seizures annotated by an expert then tested and evaluated on
another 20 seizures that were annotated by 11 experts.
PMID- 29346107
TI - Brain MR Image Restoration Using an Automatic Trilateral Filter With GPU-Based
Acceleration.
AB - OBJECTIVE: Noise reduction in brain magnetic resonance (MR) images has been a
challenging and demanding task. This study develops a new trilateral filter that
aims to achieve robust and efficient image restoration. METHODS: Extended from
the bilateral filter, the proposed algorithm contains one additional intensity
similarity funct-ion, which compensates for the unique characteristics of noise
in brain MR images. An entropy function adaptive to intensity variations is
introduced to regulate the contributions of the weighting components. To hasten
the computation, parallel computing based on the graphics processing unit (GPU)
strategy is explored with emphasis on memory allocations and thread
distributions. To automate the filtration, image texture feature analysis
associated with machine learning is investigated. Among the 98 candidate
features, the sequential forward floating selection scheme is employed to acquire
the optimal texture features for regularization. Subsequently, a two-stage
classifier that consists of support vector machines and artificial neural
networks is established to predict the filter parameters for automation. RESULTS:
A speedup gain of 757 was reached to process an entire MR image volume of 256 *
256 * 256 pixels, which completed within 0.5 s. Automatic restoration results
revealed high accuracy with an ensemble average relative error of 0.53 +/- 0.85%
in terms of the peak signal-to-noise ratio. CONCLUSION: This self-regulating
trilateral filter outperformed many state-of-the-art noise reduction methods both
qualitatively and quantitatively. SIGNIFICANCE: We believe that this new image
restoration algorithm is of potential in many brain MR image processing
applications that require expedition and automation.
PMID- 29346108
TI - Modeling of Electroporation Induced by Pulsed Electric Fields in Irregularly
Shaped Cells.
AB - During the past decades, the poration of cell membrane induced by pulsed electric
fields has been widely investigated. Since the basic mechanisms of this process
have not yet been fully clarified, many research activities are focused on the
development of suitable theoretical and numerical models. To this end, a
nonlinear, nonlocal, dispersive, and space-time numerical algorithm has been
developed and adopted to evaluate the transmembrane voltage and pore density
along the perimeter of realistic irregularly shaped cells. The presented model is
based on the Maxwell's equations and the asymptotic Smoluchowski's equation
describing the pore dynamics. The dielectric dispersion of the media forming the
cell has been modeled by using a general multirelaxation Debye-based formulation.
The irregular shape of the cell is described by using the Gielis' superformula.
Different test cases pertaining to red blood cells, muscular cells, cell in
mitosis phase, and cancer-like cell have been investigated. For each type of
cell, the influence of the relevant shape, the dielectric properties, and the
external electric pulse characteristics on the electroporation process has been
analyzed. The numerical results demonstrate that the proposed model is an
efficient numerical tool to study the electroporation problem in arbitrary-shaped
cells.
PMID- 29346109
TI - Endocardial Energy Harvesting by Electromagnetic Induction.
AB - OBJECTIVE: cardiac pacemakers require regular medical follow-ups to ensure proper
functioning. However, device replacements due to battery depletion are common and
account for ~25% of all implantation procedures. Furthermore, conventional
pacemakers require pacemaker leads which are prone to fractures, dislocations or
isolation defects. The ensuing surgical interventions increase risks for the
patients and costs that need to be avoided. METHODS: in this study, we present a
method to harvest energy from endocardial heart motions. We developed a novel
generator, which converts the heart's mechanical into electrical energy by
electromagnetic induction. A mathematical model has been introduced to identify
design parameters strongly related to the energy conversion efficiency of heart
motions and fit the geometrical constraints for a miniaturized transcatheter
deployable device. The implemented final design was tested on the bench and in
vivo. RESULTS: the mathematical model proved an accurate method to estimate the
harvested energy. For three previously recorded heart motions, the model
predicted a mean output power of 14.5, 41.9, and 16.9 MUW. During an animal
experiment, the implanted device harvested a mean output power of 0.78 and 1.7
MUW at a heart rate of 84 and 160 bpm, respectively. CONCLUSION: harvesting
kinetic energy from endocardial motions seems feasible. Implanted at an
energetically favorable location, such systems might become a welcome alternative
to extend the lifetime of cardiac implantable electronic device. SIGNIFICANCE:
the presented endocardial energy harvesting concept has the potential to turn
pacemakers into battery- and leadless systems and thereby eliminate two major
drawbacks of contemporary systems.
PMID- 29346110
TI - A Three-Dimensional Arrayed Microfluidic Blood-Brain Barrier Model With
Integrated Electrical Sensor Array.
AB - OBJECTIVE: The blood-brain barrier (BBB) poses a unique challenge to the
development of therapeutics against neurological disorders due to its impermeabi
lity to most of the chemical compounds. Most in vitro BBB models have limitations
in mimicking in vivo conditions and functions. Here, we show a co-culture
microfluidic BBB-on-a-chip that provides interactions between neurovascular
endothelial cells and neuronal cells across a porous polycarbonate membrane,
which better mimics the in vivo conditions, as well as allows in vivo level shear
stress to be applied. METHODS: A 4 * 4 intersecting microchannel array forms 16
BBB sites on a chip, with a multielectrode array integrated to measure the
transendothelial electrical resistance (TEER) from all 16 different sites, which
allows label-free real-time analysis of the barrier function. Primary mouse
endothelial cells and primary astrocytes were co-cultured in the chip while
applying in vivo level shear stress. The chip allows the barrier function to be
analyzed through TEER measurement, dextran permeability, as well as
immunostaining. RESULTS: Co-culture between astrocytes and endothelial cells, as
well as in vivo level shear stress applied, led to the formation of tighter
junctions and significantly lower barrier permeability. Moreover, drug testing
with histamine showed increased permeability when using only endothelial cells
compared to almost no change when using co-culture. CONCLUSION: Results show that
the developed BBB chip more closely mimics the in vivo BBB environment.
SIGNIFICANCE: The developed multisite BBB chip is expected to be used for
screening drug by more accurately predicting their permeability through BBB as
well as their toxicity.
PMID- 29346111
TI - Single-Scan High-Resolution 2-D $J$ -Resolved Spectroscopy in Inhomogeneous
Magnetic Fields.
AB - OBJECTIVE: A method is proposed to obtain high-resolution 2-D -resolved nuclear
magnetic resonance (NMR) spectra in inhomogeneous magnetic fields. METHODS: The
proposed experiment enables the acquisition of an entire 2-D spectrum in a single
scan by utilizing intermolecular double-quantum coherences and the spatial
encoding of NMR observables. RESULTS: Chemical shifts, coupling constants, and
multiplet patterns are recovered even when field inhomogeneities are severe
enough to completely obscure conventional NMR spectra. After intentional
deshimming to yield inhomogeneous magnetic fields, the method was demonstrated on
ethyl 3-bromoproprionate in acetone and on a complex mixture of organic
compounds. To illustrate the technique's applicability to biological samples with
intrinsic magnetic field inhomogeneities arising from macroscopic magnetic
susceptibility variations, we performed the experiment on a pig bone marrow
sample. CONCLUSION: Our results show that the new method is a fast and effective
tool for studying complex chemical mixtures and biological tissues. SIGNIFICANCE:
The method could potentially be useful for real-time in vivo NMR studies.
PMID- 29346112
TI - Numerical Model Reduction for the Prediction of Interface Pressure Applied by
Compression Bandages on the Lower Leg.
AB - OBJECTIVE: To develop a new method for the prediction of interface pressure
applied by medical compression bandages. METHODS: A finite element simulation of
bandage application was designed, based on patient-specific leg geometries. For
personalized interface pressure prediction, a model reduction approach was
proposed, which included the parametrization of the leg geometry. Pressure values
computed with this reduced model were then confronted to experimental pressure
values. RESULTS: The most influencing parameters were found to be the bandage
tension, the skin-to-bandage friction coefficient and the leg morphology. Thanks
to the model reduction approach, it was possible to compute interface pressure as
a linear combination of these parameters. The pressures computed with this
reduced model were in agreement with experimental pressure values measured on 66
patients' legs. CONCLUSION: This methodology helps to predict patient-specific
interface pressure applied by compression bandages within a few minutes whereas
it would take a few days for the numerical simulation. The results of this method
show less bias than Laplace's Law, which is for now the only other method for
interface pressure computation.
PMID- 29346113
TI - Uncertainty in Limb Configuration Makes Minimal Contribution to Errors Between
Observed and Predicted Forces in a Musculoskeletal Model of the Rat Hindlimb.
AB - Subject-specific musculoskeletal models are increasingly used in biomedical
applications to predict endpoint forces due to muscle activation, matching
predicted forces to experimentally observed forces at a specific limb
configuration. However, it is difficult to precisely measure the limb
configuration at which these forces are observed. The consequent uncertainty in
limb configuration might contribute to errors in model predictions. We therefore
evaluated how uncertainties in limb configuration measurement contributed to
errors in force prediction, using data from in vivo measurements in the rat
hindlimb. We used a data-driven approach to estimate the uncertainty in estimated
limb configuration and then used this configuration uncertainty to evaluate the
consequent uncertainty in force predictions, using Monte Carlo simulations. We
used subject-specific models of joint structures (i.e., centers and axes of
rotation) in order to estimate limb configurations for each animal. The standard
deviation of the distribution of predicted force directions resulting from
configuration uncertainty was small, ranging between 0.27 degrees and 3.05
degrees across muscles. For most muscles, this standard deviation was
considerably smaller than the error between observed and predicted forces
(between 0.57 degrees and 70.96 degrees ), suggesting that uncertainty in limb
configuration could not explain inaccuracies in model predictions. Instead, our
results suggest that inaccuracies in muscle model parameters, most likely in
parameters specifying muscle moment arms, are the main source of prediction
errors by musculoskeletal models in the rat hindlimb.
PMID- 29346114
TI - OR.NET: a service-oriented architecture for safe and dynamic medical device
interoperability.
AB - Modern surgical departments are characterized by a high degree of automation
supporting complex procedures. It recently became apparent that integrated
operating rooms can improve the quality of care, simplify clinical workflows, and
mitigate equipment-related incidents and human errors. Particularly using
computer assistance based on data from integrated surgical devices is a promising
opportunity. However, the lack of manufacturer-independent interoperability often
prevents the deployment of collaborative assistive systems. The German flagship
project OR.NET has therefore developed, implemented, validated, and standardized
concepts for open medical device interoperability. This paper describes the
universal OR.NET interoperability concept enabling a safe and dynamic
manufacturer-independent interconnection of point-of-care (PoC) medical devices
in the operating room and the whole clinic. It is based on a protocol
specifically addressing the requirements of device-to-device communication, yet
also provides solutions for connecting the clinical information technology (IT)
infrastructure. We present the concept of a service-oriented medical device
architecture (SOMDA) as well as an introduction to the technical specification
implementing the SOMDA paradigm, currently being standardized within the IEEE
11073 service-oriented device connectivity (SDC) series. In addition, the Session
concept is introduced as a key enabler for safe device interconnection in highly
dynamic ensembles of networked medical devices; and finally, some security
aspects of a SOMDA are discussed.
PMID- 29346115
TI - Mitochondrial dysfunction: a key player in the pathogenesis of cardiovascular
diseases linked to air pollution.
AB - Air pollution has become an environmental burden with regard to non-communicable
diseases, particularly heart disease. It has been reported that air pollution can
accelerate the development of heart failure and atrial fibrillation. Air
pollutants encompass various particulate matters (PMs), which change the blood
composition and heart rate and eventually leads to cardiac failure by triggering
atherosclerotic plaque ruptures or by developing irreversible ischemia. A series
of major epidemiological and observational studies have established the noxious
effect of air pollutants on cardiovascular diseases (CVD), but the underlying
molecular mechanisms of its susceptibility and the pathological disease events
remain largely elusive and are predicted to be initiated in the cell organelle.
The basis of this belief is that mitochondria are one of the major targets of
environmental toxicants that can damage mitochondrial morphology, function and
its DNA (manifested in non-communicable diseases). In this article, we review the
literature related to air pollutants that adversely affect the progression of CVD
and that target mitochondrial morphological and functional activities and how
mitochondrial DNA (mtDNA) copy number variation, which reflects the airborne
oxidant-induced cell damage, correlates with heart failure. We conclude that
environmental health assessment should focus on the cellular/circulatory
mitochondrial functional copy number status, which can predict the outcome of
CVD.
PMID- 29346116
TI - 4D computed tomography scans for conformal thoracic treatment planning: is a
single scan sufficient to capture thoracic tumor motion?
AB - Four dimensional computed tomography (4DCT) scans are routinely used in radiation
therapy to determine the internal treatment volume for targets that are moving
(e.g. lung tumors). The use of these studies has allowed clinicians to create
target volumes based upon the motion of the tumor during the imaging study. The
purpose of this work is to determine if a target volume based on a single 4DCT
scan at simulation is sufficient to capture thoracic motion. Phantom studies were
performed to determine expected differences between volumes contoured on 4DCT
scans and those on the evaluation CT scans (slow scans). Evaluation CT scans
acquired during treatment of 11 patients were compared to the 4DCT scans used for
treatment planning. The images were assessed to determine if the target remained
within the target volume determined during the first 4DCT scan. A total of 55
slow scans were compared to the 11 planning 4DCT scans. Small differences were
observed in phantom between the 4DCT volumes and the slow scan volumes, with a
maximum of 2.9%, that can be attributed to minor differences in contouring and
the ability of the 4DCT scan to adequately capture motion at the apex and base of
the motion trajectory. Larger differences were observed in the patients studied,
up to a maximum volume difference of 33.4%. These results demonstrate that a
single 4DCT scan is not adequate to capture all thoracic motion throughout
treatment.
PMID- 29346118
TI - Mycobacterium avium complex pulmonary disease: new epidemiology and management
concepts.
AB - PURPOSE OF REVIEW: The prevalence of Mycobacterium avium complex (MAC)-related
pulmonary disease has been increasing because of environmental factors, changes
in organism virulence, and evolving host susceptibility. Treatment is often
complicated by adverse effects, development of drug resistance, and refractory
disease, with recurrence rates as high as 25-45%. RECENT FINDINGS: Aerosolization
of water, soil, or dusts are the likely sources of MAC-related pulmonary disease
in susceptible individuals. The management of MAC-related pulmonary disease
requires a multimodality approach, including antimicrobial therapy in appropriate
patients, employment of mucus clearance techniques, instituting changes in the
individual's home environment and personal habits to reduce environmental
exposure to MAC, prevention of reflux, and maintenance of a healthy body weight.
When the standard treatment for MAC-related pulmonary disease is not possible
because of drug intolerance, antibiotic resistance, or progression of disease,
second-line agents such as inhaled amikacin, clofazimine, bedaquiline, and
delamanid must be considered, despite limited experience and few studies to guide
their use. SUMMARY: Individuals who have proven to be susceptible to MAC-related
pulmonary disease should institute measures to reduce exposure to environmental
sources of infection. Further research is needed to assess the impact of such
preventive strategies on the incidence of new infection and disease recurrence.
The efficacy of new medications for MAC-related pulmonary disease and their use
in different combinations also requires further study.
PMID- 29346117
TI - The deubiquitinase USP9X regulates FBW7 stability and suppresses colorectal
cancer.
AB - The tumor suppressor FBW7 targets oncoproteins such as c-MYC for ubiquitylation
and is mutated in several human cancers. We noted that in a substantial
percentage of colon cancers, FBW7 protein is undetectable despite the presence of
FBW7 mRNA. To understand the molecular mechanism of FBW7 regulation in these
cancers, we employed proteomics and identified the deubiquitinase (DUB) USP9X as
an FBW7 interactor. USP9X antagonized FBW7 ubiquitylation, and Usp9x deletion
caused Fbw7 destabilization. Mice lacking Usp9x in the gut showed reduced
secretory cell differentiation and increased progenitor proliferation,
phenocopying Fbw7 loss. In addition, Usp9x inactivation impaired intestinal
regeneration and increased tumor burden in colitis-associated intestinal cancer.
c-Myc heterozygosity abrogated increased progenitor proliferation and tumor
burden in Usp9x-deficient mice, suggesting that Usp9x suppresses tumor formation
by regulating Fbw7 protein stability and thereby reducing c-Myc. Thus, we
identify a tumor suppressor mechanism in the mammalian intestine that arises from
the posttranslational regulation of FBW7 by USP9X independent of somatic FBW7
mutations.
PMID- 29346119
TI - The role of tedizolid in skin and soft tissue infections.
AB - PURPOSE OF REVIEW: Tedizolid is a second-generation oxazolidinone with activity
against Gram-positive bacteria, including MRSA isolates resistant to linezolid.
Pivotal clinical trials showed that tedizolid at 200 mg once-daily for 6 days is
not inferior to linezolid 600 mg twice daily for 10 days in patients with SSTI.
The comparison of adverse events is favorable to tedizolid under the
circumstances of the clinical trials. This is a review of recent literature on
tedizolid, its use in special populations and potential adverse effects. RECENT
FINDINGS: Findings suggest that tedizolid can be used in SSTI in adolescents,
those older than 65 years, obese individuals and patients with diabetic foot
infections. Forthcoming research to determine the future uses of this drug in
other clinical syndromes requires demonstration of tolerance whenever tedizolid
is administered for longer than 6 days.We also speculate on missing data and
potential future indications of tedizolid in the highly competitive field of the
treatment of severe Gram-positive infections other than SSTI. SUMMARY: Tedizolid
is a second-generation oxazolidinone, very convenient for treatment of SSTI, in
search for other indications including nosocomial pneumonia and bone and joint
infections. VIDEO ABSTRACT.
PMID- 29346120
TI - A View From the UK: The UK and Ireland Confidential Enquiry into Maternal Deaths
and Morbidity.
AB - The UK Confidential Enquiry into Maternal Deaths has been in operation for more
than 60 years, during which time maternal mortality rates have fallen 10-fold.
The program includes two aspects, surveillance and confidential case review,
providing different information to aid quality improvement in maternity care. The
enquiry now also reviews the care of women with specific severe morbidities.
Recommendations have very clearly led to improved outcomes for women, most
notably shown in the very low mortality rate due to hypertensive and related
disorders of pregnancy. Maternal cardiac disease and mental health problems
remain the major areas still to be addressed.
PMID- 29346122
TI - Bolus Norepinephrine Administration and Fetal Acidosis at Cesarean Delivery Under
Spinal Anesthesia.
PMID- 29346123
TI - In Response.
PMID- 29346121
TI - Reducing Disparities in Severe Maternal Morbidity and Mortality.
AB - Significant racial and ethnic disparities in maternal morbidity and mortality
exist in the United States. Black women are 3 to 4 times more likely to die a
pregnancy-related death as compared with white women. Growing research indicates
that quality of health care, from preconception through postpartum care, may be a
critical lever for improving outcomes for racial and ethnic minority women. This
article reviews racial and ethnic disparities in severe maternal morbidities and
mortality, underlying drivers of these disparities, and potential levers to
reduce their occurrence.
PMID- 29346124
TI - In Response.
PMID- 29346125
TI - The Unknown Mechanism of Exogenous Tetrahydrobiopterin in the Renal Protection of
Sheep Ischemia and Reperfusion.
PMID- 29346126
TI - Complete revascularization for patients with ST-segment elevation myocardial
infarction and multivessel coronary artery disease: a meta-analysis of randomized
trials.
AB - INTRODUCTION: Despite the recent findings in randomized clinical trials (RCTs)
with limited sample sizes and the updates in clinical guidelines, the current
available data for the complete revascularization (CR) in hemodynamically stable
patients with ST-segment elevation myocardial infarction (STEMI) at the time of
primary percutaneous coronary intervention (PCI) are still contradictory. AIM:
The aim of this meta-analysis of the existing RCTs was to assess the efficacy of
the CR versus revascularization of infarct-related artery (IRA) only during
primary PCI in patients with STEMI and multivessel disease (MVD). PATIENTS AND
METHODS: We searched PubMed, MEDLINE, Embase, Scopus, Google Scholar, Cochrane
Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases
aiming to find RCTs for patients with STEMI and MVD which compared CR with IRA
only. Random effect risk ratios (RRs) were calculated for efficacy and safety
outcomes. RESULTS: Ten RCTs with 3291 patients were included. The median follow
up duration was 17.5 months. Major adverse cardiac events (RR=0.57; 0.43-0.76;
P<0.0001), cardiac mortality (RR=0.52; 0.31-0.87; P=0.014), and repeat
revascularization (RR=0.50; 0.30-0.84; P=0.009) were lower in CR compared with
IRA-only strategies. However, there was no significant difference in the risk of
all-cause mortality, recurrent nonfatal myocardial infarction, stroke, major
bleeding events, and contrast-induced nephropathy. CONCLUSION: For patients with
STEMI and MVD undergoing primary PCI, the current evidence suggests that the risk
of major adverse cardiac events, repeat revascularization, and cardiac death is
reduced by CR. However, the risk for all-cause mortality and PCI-related
complications is not different from the isolated culprit lesion-only treatment.
Although these findings support the cardiac mortality and safety benefit of CR in
stable STEMI, further large trials are required to provide better guidance for
optimum management of such patients.
PMID- 29346127
TI - Rivaroxaban with or without aspirin for prevention of cardiovascular disease.
PMID- 29346128
TI - Management of heavy menstrual bleeding during direct oral anticoagulant therapy
for recurrent venous thromboembolism: a case report.
AB - : A high risk of venous thromboembolism (VTE) recurrence requires extended
anticoagulation but limits the options to control heavy menstrual bleeding (HMB)
in women of reproductive age. We report the management of HMB in a 48-year-old
woman with a history of menometrorrhagia, recurrent VTE and multiple VTE risk
factors. Due to the occurrence of HMB during extended rivaroxaban treatment, the
presence of a uterine fibroid and the contraindication to interrupt
anticoagulation for high risk of VTE recurrence, she received hormonal treatment
first with a gonadotropin-releasing hormone agonist and then with progestin. This
strategy allowed to adequately control HMB, without rivaroxaban discontinuation
or dose reduction, and no new thromboembolic and no more bleeding events occurred
over a long follow-up period of more than 20 months. In conclusion, the use of
hormonal therapy in VTE women requiring long-term anticoagulation may be an
option to control HMB, without further increasing the risk of VTE recurrence.
PMID- 29346129
TI - High Inflammatory Infiltrate Correlates With Poor Symptomatic Improvement After
Surgical Treatment for Superior Limbic Keratoconjunctivitis.
AB - PURPOSE: Superior limbic keratoconjunctivitis (SLK) is a chronic and recurrent
condition of unknown etiology. It is often managed conservatively, but there is a
high rate of success with surgical management for severe or recalcitrant cases.
The purpose of this article is to describe and analyze clinicopathological
features of patients with SLK who underwent surgical treatment and their
association with the clinical outcome. METHODS: A total of 22 eyes from 18
patients who underwent surgical SLK management were retrospectively analyzed.
Clinicopathological data were collected including details of follow-up and
patient satisfaction (n = 15). Moreover, 12 cases had specimens available for
review of histopathologic findings and COX-2 expression analysis by
immunohistochemistry. RESULTS: From a clinical perspective, 66.7% of the SLK eyes
had nonmechanical factors contributing to SLK, and 66.7% of eyes demonstrated
significant symptomatic improvement after surgery. Histopathological analysis of
all the lesions showed acanthosis and goblet cell loss. Unexpectedly, in 93% of
the eyes, dilated lymphatic vessels were found. Furthermore, a high inflammatory
infiltrate correlated with minimal symptomatic improvements (P = 0.013).
Moreover, COX-2 expression was higher in patients with SLK than in a normal
conjunctiva (P = 0.001). CONCLUSIONS: In this study, the most common systemic
association with SLK was the patient's autoimmune status. Histopathological
evaluation revealed that high inflammatory infiltration in the biopsy might be
predictive of minimal symptomatic improvement with surgical management. Finally,
the higher COX-2 expression in patients with SLK compared with that in
individuals with a normal conjunctiva supports the use of anti-COX-2 drugs as a
possible therapeutic target.
PMID- 29346130
TI - Reply: Management of Descemet Membrane Detachment After Forceps Birth Injury.
PMID- 29346131
TI - Toxicological profile and safety pharmacology of a single dose of fibroblast
activation protein-alpha-based doxorubicin prodrug: in-vitro and in-vivo
evaluation.
AB - Fibroblast activation protein-alpha (FAPalpha) is a promising tumor-associated
target expressed by reactive stromal fibroblasts in tumor tissue. FAPalpha has a
postprolyl peptidase activity and can specifically cleave N-terminal
benzyloxycarbonyl (Z)-blocked peptides, such as the substrate Z-Gly-Pro-AMC.
Doxorubicin (DOX) is an effective antitumor drug, but its application is greatly
limited by toxic adverse effects owing to poor tumor selectivity. Based on these
facts, we previously designed a FAPalpha-targeting prodrug of doxorubicin (FTPD)
which can be selectively hydrolyzed by FAPalpha. FTPD can retain potent antitumor
efficacy and has favorable tumor targeting. The present study aimed to further
evaluate the toxicological profile and the safety pharmacological property of
FTPD in vitro and in vivo. The cytotoxicity assay showed that FTPD displayed
markedly lower cytotoxicity to 3T3 cells and HEK-293 cells compared with DOX. In
the short-term toxicity study, mice treated with 25 mg/kg of FTPD showed no
obvious change in the appearance and general behavior, and no case of mortality
was observed within 14 days. Unlike DOX, FTPD exhibited reduced toxicity to
heart, liver, kidney, spleen as well as peripheral white blood cells in mice.
Moreover, open file test and general pharmacology study were also conducted
correspondingly in mice and beagle dogs. It was found that FTPD may not produce
significant pharmacological effects on spontaneous locomotor activity and
cardiovascular-respiratory system except for a transient decreasing in systolic
blood pressure. Taken together, the results of this work suggest that FTPD has
more favorable toxicological profile and better drug safety compared with its
parent drug DOX.
PMID- 29346132
TI - Enzymatic sources and physio-pathological functions of soluble (pro)renin
receptor.
AB - PURPOSE OF REVIEW: (Pro)renin receptor (PRR) belongs to type I transmembrane
receptor family and binds both prorenin and renin, representing a potential
regulator of the activity of the renin-angiotensin system. Soluble form of PRR
(sPRR) is generated by intracellular protease-mediated cleavage of full-length
PRR. The purpose of this review is to highlight recent advances in understanding
the mechanisms of action and production of sPRR. RECENT FINDINGS: It has recently
been demonstrated that site-1-protease (S1P) plays a dominant role in the
generation of sPRR. New evidence is also emerging to support a biological
function of sPRR in the physiological regulation of fluid homeostasis as well as
pathogenesis of chronic kidney disease. SUMMARY: sPRR is a 28 kDa product of PRR
cleavage via S1P-mediated protease activity. Not only does sPRR regulate renal
tubular water transport, but it also mediates pathogenic responses to renal
cellular injury. sPRR is likely involved in a wide range of physio-pathological
processes.
PMID- 29346133
TI - Dexmedetomidine Impairs Diaphragm Function and Increases Oxidative Stress but
Does Not Aggravate Diaphragmatic Atrophy in Mechanically Ventilated Rats.
AB - BACKGROUND: Anesthetics in ventilated patients are critical as any cofactor
hampering diaphragmatic function may have a negative impact on the weaning
progress and therefore on patients' mortality. Dexmedetomidine may display
antioxidant and antiproteolytic properties, but it also reduced glucose uptake by
the muscle, which may impair diaphragm force production. This study tested the
hypothesis that dexmedetomidine could inhibit ventilator-induced diaphragmatic
dysfunction. METHODS: Twenty-four rats were separated into three groups (n =
8/group). Two groups were mechanically ventilated during either dexmedetomidine
or pentobarbital exposure for 24 h, referred to as interventional groups. A third
group of directly euthanized rats served as control. Force generation, fiber
dimensions, proteolysis markers, protein oxidation and lipid peroxidation,
calcium homeostasis markers, and glucose transporter-4 (Glut-4) translocation
were measured in the diaphragm. RESULTS: Diaphragm force, corrected for cross
sectional area, was significantly decreased in both interventional groups
compared to controls and was significantly lower with dexmedetomidine compared to
pentobarbital (e.g., 100 Hz: -18%, P < 0.0001). In contrast to pentobarbital,
dexmedetomidine did not lead to diaphragmatic atrophy, but it induced more
protein oxidation (200% vs. 73% in pentobarbital, P = 0.0015), induced less
upregulation of muscle atrophy F-box (149% vs. 374% in pentobarbital, P < 0.001)
and impaired Glut-4 translocation (-73%, P < 0.0005). It activated autophagy, the
calcium-dependent proteases, and caused lipid peroxidation similarly to
pentobarbital. CONCLUSIONS: Twenty-four hours of mechanical ventilation during
dexmedetomidine sedation led to a worsening of ventilation-induced diaphragm
dysfunction, possibly through impaired Glut-4 translocation. Although
dexmedetomidine prevented diaphragmatic fiber atrophy, it did not inhibit
oxidative stress and activation of the proteolytic pathways.
PMID- 29346134
TI - Effect of Maternal Body Mass Index on Postpartum Hemorrhage.
AB - BACKGROUND: It is unclear whether obesity is a risk factor for postpartum
hemorrhage. The authors hypothesized that obese women are at greater risk of
hemorrhage than women with a normal body mass index. METHODS: The authors
conducted a cohort study of women who underwent delivery hospitalization in
California between 2008 and 2012. Using multilevel regression, the authors
examined the relationships between body mass index with hemorrhage (primary
outcome), atonic hemorrhage, and severe hemorrhage (secondary outcomes).
Stratified analyses were performed according to delivery mode. RESULTS: The
absolute event rate for hemorrhage was 60,604/2,176,673 (2.8%). In this cohort,
4% of women were underweight, 49.1% of women were normal body mass index, 25.9%
of women were overweight, and 12.7%, 5.2%, and 3.1% of women were in obesity
class I, II, and III, respectively. Compared to normal body mass index women, the
odds of hemorrhage and atonic hemorrhage were modestly increased for overweight
women (hemorrhage: adjusted odds ratio [aOR], 1.06; 99% CI, 1.04 to 1.08; atonic
hemorrhage: aOR, 1.07; 99% CI, 1.05 to 1.09) and obesity class I (hemorrhage:
aOR, 1.08; 99% CI, 1.05 to 1.11; atonic hemorrhage; aOR, 1.11; 99% CI, 1.08 to
1.15). After vaginal delivery, overweight and obese women had up to 19% increased
odds of hemorrhage or atonic hemorrhage; whereas, after cesarean delivery, women
in any obesity class had up to 14% decreased odds of severe hemorrhage.
CONCLUSIONS: The authors' findings suggest that, at most, maternal obesity has a
modest effect on hemorrhage risk. The direction of the association between
hemorrhage and body mass index may differ by delivery mode.
PMID- 29346135
TI - Behavioral Health Training in Pediatric Residency Programs: A National Survey of
Training Directors.
AB - OBJECTIVE: To identify perceptions of behavioral health (BH) training in
pediatric residency programs, the degree of involvement from behavioral health
providers (BHPs), and opportunities for and barriers to innovation in training.
METHOD: A tailored design methodology was used to target all pediatric residency
program directors in the United States (N = 214). Participants were identified
from the Electronic Residency Application Service website of the Association of
American Medical Colleges and were asked to complete a 22-item item survey on BH
training. RESULTS: A 69.2% usable response rate (N = 148) was obtained. A total
of 62.8% of directors described training in the developmental-behavioral
pediatrics (DBP) rotation as optimal; 36% described BH training in the residency
program as a whole (i.e., outside the DBP rotation) as optimal. Only 20.3%
described "common factors" training as optimal, and the quality of training in
this area was positively and significantly related to the quality of BH training
in the residency program as a whole (chi = 35.05, p < 0.001). The quality of
common factors training was significantly higher in programs that had embedded
BHPs (i.e., psychologists and social workers) in the continuity clinic than
programs that did not (chi = 7.65, p = 0.04). Barriers to quality training
included instructional content, instructional methods, stakeholder support, and
resources. CONCLUSION: Despite substantial improvement in residency training in
BH over the last decade, additional improvement is needed. Barriers to continued
improvement include training content, training methods, support from faculty and
administrator stakeholders, and resource issues. Strategies derived from
implementation science have the potential to address these barriers.
PMID- 29346136
TI - Interdisciplinary Team Evaluation: An Effective Method for the Diagnostic
Assessment of Autism Spectrum Disorder.
AB - OBJECTIVE: The objective of this research is to assess the feasibility of an
interdisciplinary team diagnostic assessment model for autism spectrum disorder
(ASD). METHOD: Medical records from 366 patients evaluated for ASD at the Seattle
Children's Autism Center (SCAC) were reviewed. ASD diagnostic outcomes, provider
satisfaction, engagement in follow-up care, billed time, and reimbursement
amounts were compared in patients evaluated through an interdisciplinary team
approach (n = 91) with those seen in multidisciplinary evaluations led by either
a psychologist (n = 165) or a physician (n = 110). RESULTS: Diagnostic
determination was made in 90% of patients evaluated through the interdisciplinary
team model in a single day. Rates of ASD diagnosis were similar across the 3
tracks, ranging from 61% to 72%. Demographic characteristics did not impact the
likelihood of ASD diagnosis. Rates of patient follow-up care and provider
satisfaction were significantly higher in interdisciplinary versus
multidisciplinary teams. Interdisciplinary team evaluations billed 1.8 fewer
hours yet generated more net hourly clinic income compared with psychology-led
multidisciplinary evaluations. CONCLUSION: An interdisciplinary team approach,
focusing on ruling-in or ruling-out ASD, was sufficient to determine ASD
diagnosis in most patients seen at the SCAC Interdisciplinary teams generated
more clinic income and decreased the time spent in evaluation compared with a
psychology-led approach. They did so while maintaining consistency in diagnostic
rates, demonstrating increased provider satisfaction and an increased likelihood
of engagement in follow-up care.
PMID- 29346137
TI - Guidance Provided to Authors on Citing and Formatting References in Nursing
Journals.
AB - Reference citations should be accurate, complete, and presented in a consistent
format. This study analyzed information provided to authors on preparing
citations and references for manuscripts submitted to nursing journals (n = 209).
Half of the journals used the American Psychological Association reference style.
Slightly more than half provided examples of how to cite articles and books;
there were fewer examples of citing websites and online journals. Suggestions on
improving accuracy of references are discussed.
PMID- 29346138
TI - Obesity and chronic kidney disease.
AB - PURPOSE OF REVIEW: To review recent advances in the epidemiology,
pathophysiology, clinical features, and treatment of obesity-related kidney
disease. RECENT FINDINGS: Studies have confirmed that obesity is associated with
increased risk of developing chronic kidney disease (CKD). This risk extends to
those who are metabolically healthy, indicating that obesity per se contributes
to CKD independent of the metabolic syndrome. Recent developments in the
pathophysiology of obesity-related kidney disease indicate that chronic
inflammation and abnormal lipid metabolism contribute to kidney cell injury.
Children with severe obesity have increased prevalence of early kidney
abnormalities, including albuminuria, decreased kidney function, and elevated
biomarkers of early kidney injury. For these patients, bariatric surgery has
emerged as a treatment option to consider. Longitudinal studies in children and
adults have demonstrated that in patients with obesity-related kidney disease,
kidney function and albuminuria improve following bariatric surgery. SUMMARY: The
injurious renal effects of obesity are present in childhood, although the natural
history and clinical spectrum of obesity-related kidney disease in children are
not known. In obese children with early kidney disease, identification of kidney
injury, implementation of preventive strategies, and prompt treatment are
essential to improving clinical outcomes.
PMID- 29346139
TI - Blood biomarkers for evaluation of perinatal encephalopathy: state of the art.
AB - PURPOSE OF REVIEW: The rapid progress in biomarker science is on the threshold of
significantly changing clinical care for infants in the neonatal ICU. Infants
with neonatal brain injuries will likely be the first group whose management is
dramatically altered with point-of-care, rapidly available brain biomarker
analysis. Providing an interim update on progress in this area is the purpose of
this review. RECENT FINDINGS: Highlighted findings from the past 18 months of
publications on biomarkers in neonatal brain injury include; Specific nonbrain
markers of cardiac health and global asphyxia continue to provide information on
brain injury after hypoxic-ischemic encephalopathy (HIE). Prediction of injury in
the piglet hypoxia-ischemia model is improved with the use of a combination score
of plasma metabolites. In a neonatal piglet model of perinatal hypoxia-ischemia,
a systemic proinflammatory surge of cytokines has been identified after rewarming
from therapeutic hypothermia. New biomarkers identified recently include
osteopontin, activin A, neutrophil gelatinase-associated lipocalin,
secretoneurin, Tau and neurofilament light protein. Brain-based biomarkers differ
in their ability to predict short-term in-hospital outcomes and long-term
neurologic deficits. SUMMARY: Neonatal brain biomarker research is currently in
its very early development with major advances still to be made.
PMID- 29346140
TI - Neonatal hypoglycemia: continuous glucose monitoring.
AB - PURPOSE OF REVIEW: Continuous glucose monitoring (CGM) is increasingly used in
the management of diabetes in children and adults, but there are few data
regarding its use in neonates. The purpose of this article is to discuss the
potential benefits and limitations of CGM in neonates. RECENT FINDINGS: Smaller
electrodes in new sensors and real-time monitoring have made CGM devices more
approachable for neonatal care. CGM is well tolerated in infants including very
low birth weight babies, and few if any local complications have been reported.
Use of CGM in newborns may reduce the frequency of blood sampling and improve
glycemic stability, with more time spent in the euglycemic range. However, CGM
may also lead to more intervention, with potential adverse effects on outcomes.
More information is also needed about reliability, calibration and interpretation
of CGM in the neonate. SUMMARY: Although the use of CGM in neonates appears to be
well tolerated, feasible and has been associated with better glycemic status,
there is not yet any evidence of improved clinical outcomes. Clinical utility of
CGM should be demonstrated in randomized trials prior to its introduction into
regular neonatal care.
PMID- 29346141
TI - Caffeine controversies.
AB - PURPOSE OF REVIEW: Caffeine use in preterm infants has endured several paradigms:
from standard of care to possible neurotoxin to one of the few medications for
which there is evidence of bronchopulmonary dysplasia (BPD) risk reduction. The
purpose of the review is to analyze this dynamic trajectory and discuss
controversies that still remain after decades of caffeine use. RECENT FINDINGS:
Following concerns for caffeine safety in preterm infants, a large randomized
controlled trial demonstrated a reduction in BPD and treatment for patent ductus
arteriosus. The lower rate of death or neurodevelopmental impairment noted at 18
21 months was not statistically different at later timepoints; however, infants
in the caffeine group had lower rates of motor impairment at 11-year follow-up.
The time of caffeine therapy initiation is now substantially earlier, and doses
used are sometimes higher that previously used, but there are limited data to
support these practices. SUMMARY: Caffeine therapy for apnea of prematurity (AOP)
remains one of the pillars of neonatal care, although more evidence to support
dosing and timing of initiation and discontinuation are needed.
PMID- 29346142
TI - Neonatal abstinence syndrome: an update.
AB - PURPOSE OF REVIEW: The current review provides an update focused on the evolving
epidemiology of neonatal abstinence syndrome (NAS), factors influencing disease
expression, advances in clinical assessment of withdrawal, novel approaches to
NAS treatment, and the emerging role of quality improvement in assessment and
management of NAS. RECENT FINDINGS: The rise in the incidence of NAS
disproportionately occurred in rural and suburban areas. Polysubstance exposure
and genetic polymorphisms have been shown to modify NAS expression and severity.
New bedside assessments using a limited number of factors to identify infants
with NAS result in fewer infants receiving pharmacotherapy. In addition,
buprenorphine may be a promising therapeutic alternative to morphine to treat
NAS. Lastly, local, state, and national quality improvement initiatives have
emerged as an effective mechanism to advance the care of infants with NAS.
SUMMARY: NAS remains a critical public health issue associated with significant
medical, economic, and personal burdens. Emerging data on associated risk
factors, assessment of and treatment for NAS provide clinicians and hospitals
with new knowledge and an urgency to promote standardization of care for infants
with NAS.
PMID- 29346143
TI - Progression of chronic kidney disease in children.
PMID- 29346144
TI - Making Keys, Looking for Locks: Technology-Driven Versus Patient-Focused Medical
Devices.
PMID- 29346145
TI - Diagnostic and Therapeutic Ultrasound on Venous and Arterial Ulcers: A Focused
Review.
AB - GENERAL PURPOSE: To provide information about the use of ultrasound for
diagnostic and therapeutic treatment of venous and arterial ulcers. TARGET
AUDIENCE: This continuing education activity is intended for physicians,
physician assistants, nurse practitioners, and nurses with an interest in skin
and wound care. LEARNING OBJECTIVES/OUTCOMES: After completing this continuing
education activity, you should be able to: ABSTRACT: To review the diagnostic and
therapeutic use of ultrasound on venous and arterial ulcers. METHODS: PubMed was
searched for peer-reviewed articles using the search terms "ultrasound for venous
ulcers" and "ultrasound for arterial ulcers." The search yielded 282 articles on
ultrasound for venous ulcers and 455 articles for ultrasound on arterial ulcers.
Data from 36 articles were selected and included after abstract review. RESULTS:
Ultrasound is an established diagnostic modality for venous and arterial disease
and is indicated for wound debridement. Recent evidence continues to support its
superiority over standard of care in healing venous ulcers, but findings conflict
in terms of the effectiveness of low-frequency ultrasound over high-frequency
ultrasound. There are currently no standardized treatment protocols for
ultrasound. CONCLUSIONS: Diagnostic ultrasound is used to assess venous and
arterial disease and guide appropriate treatment for ulcers. Therapeutic low
frequency ultrasound is used to debride the wound bed, as an adjunctive topical
wound treatment with standard of care, and to guide the application of other
advanced therapies to chronic wounds. Better trial designs and consistent data
are needed to support the effectiveness of ultrasound therapy on venous and
arterial ulcers.
PMID- 29346146
TI - Use of Oxidized Regenerated Cellulose/Collagen Matrix in Chronic Diabetic Foot
Ulcers: A Systematic Review.
AB - OBJECTIVE: Diabetic wounds that do not heal completely usually exhibit
inflammatory markers, increased protease activity, and reduced levels of growth
factors and cell count. A systematic review was performed to determine whether
there is enough evidence to support the use of an oxidized regenerated
cellulose/collagen matrix (ORC+C) to treat diabetic foot ulcers (DFUs). METHODS:
Study authors analyzed randomized controlled trials (RCTs) on ORC+C dressings for
the treatment of DFUs. A literature search was conducted for all available
reports of relevant studies published in journals indexed in PubMed, LILACS, and
SciELO databases. There were no restrictions based on date of publication. A
population-intervention-comparison-outcome framework was built on MeSH terms and
keywords. Two independent researchers analyzed all articles for data collection
and used the Cochrane Collaboration tool for risk-of-bias assessment. RESULTS: At
first, 316 related studies were located in the databases. After evaluating these
studies for methodological similarities, only 3 were considered eligible for the
review. One RCT was considered at high risk of bias. Results from this meta
analysis of 2 studies showed no significant improvement in wound healing rates of
DFUs when ORC+C was compared with standard wound care. CONCLUSIONS: Because of
several methodology flaws in the reviewed studies, these results suggest that
there is currently no research evidence to suggest that the use of ORC+C improves
wound healing rates of DFUs. Additional research with high-quality RCTs focused
on diabetic ulcers is necessary.
PMID- 29346147
TI - Hypoperfusion and Wound Healing: Another Dimension of Wound Assessment.
AB - OBJECTIVE: To examine the correlation between mean arterial pressure (MAP) and
wound healing indices and describe an analytical process that can be used
accurately and prospectively when evaluating all types of skin ulcerations.
METHODS: A correlational study in a long-term-care facility.Participants (N =
230) were adults residing in a long-term-care facility with an average age of
77.8 years (range, 35-105). MAIN OUTCOME MEASURES: Assessment through both an
index of wound healing and wound surface area. Signs of wound healing included a
reduction of surface area and surface necrosis and increased granulation or
epithelialization. RESULTS: Aggregate analyses for all wound locations revealed a
positive correlation between the MAP and index of wound healing (r = 0.86, n =
501, P < .0001). A well-defined positive correlation between the MAP and stalled
or poor wound healing was noted for all wound locations in this data set when MAP
values were 80 mm Hg or less (r = 0.95, n = 141, P < .0001). Further, the data
set of truncal wounds and MAP of less than 80 mm Hg yielded a very strong
positive correlation. The data indicated that as perfusion decreased, wounds
within the sample population declined (r = 0.93, n = 102, P < .0001). CONCLUSION:
The data suggest that MAP values less than 80 mm Hg can independently result in
stalled wound healing or worsened wounds. A predictability of wounds stalling or
declining related to the MAP was observed, regardless of topical treatment or
standard-of-care interventions. Therefore, the data also suggest that remediating
states of low perfusion should take precedence in making treatment decisions.
PMID- 29346148
TI - Vertical Profunda Artery Perforator Flap for Plantar Foot Wound Closure: A New
Application.
AB - BACKGROUND: Plantar foot reconstruction requires special consideration of both
form and function. There are several fasciocutaneous flap options, each with
indications and reservations. CASE STUDY: This case presents a new application of
the vertical profunda artery perforator flap for definitive closure of a
neuropathic foot ulcer in a young woman with spina bifida. The postoperative
course was uneventful, and the flap survived completely. The surgical and donor
sites were without wound recurrence at 5-month follow-up. DISCUSSION:
Understanding the variability of foot flap options is important because of unique
cases such as the one presented where the wound was caused by specific and less
commonly observed foot anatomy. The specific choice to use the vertical profunda
artery perforator flap for this patient and her neuropathic wound type was made
based on its excellent flexibility, durability, and donor site appeal.
CONCLUSIONS: The vertical profunda artery perforator flap has adequate surface
area and bulk and a favorable pedicle length and caliber, can be thinned, and
leaves a donor scar in a less conspicuous area than other popular free flaps for
lower-extremity reconstruction. For these reasons, it should be considered a
first-line therapy for free flap coverage of selected foot wounds.
PMID- 29346149
TI - Testing Elevated Protease Activity: Prospective Analysis of 160 Wounds.
AB - OBJECTIVE: Given that local elevated protease activity (EPA) has been implicated
in impaired wound healing, a prospective single-center study was conducted to
assess protease activity in various wound types. METHODS: Protease activity was
determined using an easy-to-use test system (Woundchek Protease Status Test Kit;
Systagenix, Gatwick, United Kingdom) in 160 wounds in 143 patients. The assay
detects the combined activity of inflammatory proteases, mainly matrix
metalloproteinases 8 and 9 and human neutrophil elastase. RESULTS: Local EPA was
detected in 29 of 153 validly tested wounds (18.95%). No difference was detected
between acute and chronic wounds, regardless of associated or causative
conditions, with the sole exception of surgical wounds. Surgical wounds showed
EPA significantly less frequently than nonsurgical wounds. Among nonsurgical
wounds, EPA was detected more frequently in acute compared with chronic wounds.
Wounds with signs of unimpeded healing (granulation or epithelialization) showed
EPA less often than wounds covered with necrotic tissue or a fibrin layer.
However, 14% of wounds with epithelialization or granulation exhibited EPA
potentially impeding wound healing. Wounds treated with moisture-retentive wound
dressings showed EPA significantly less frequently compared with wounds bandaged
with dressings with less moisture-retentive properties. Remarkably, none of the
wounds treated with collagen/oxidized regenerated cellulose/silver, which is a
protease-modulating dressing, showed EPA. CONCLUSIONS: To the study authors'
knowledge, this is the largest study assessing EPA in various wound types. The
convenient applicability of the test system provides a basis for future studies
assessing the pathophysiologic relevance of EPA. In some unsuspicious wounds,
early detection of EPA might precede impaired healing and prompt protease
modulating treatment before failure to heal becomes apparent.
PMID- 29346150
TI - Orders and Documentation Are Vital to Diabetic Shoe Coverage.
PMID- 29346154
TI - The Cornerstone of Compliance: Your Workflow.
PMID- 29346155
TI - Diagnostic and Therapeutic Ultrasound on Venous and Arterial Ulcers: A Focused
Review.
PMID- 29346156
TI - Developing a Mobile App for Prevention and Treatment of Pressure Injuries.
AB - OBJECTIVE: This descriptive study describes the planning and development of a
mobile application (app) for prevention and treatment of pressure injuries for
use by providers in a university research center. The app delineates risk factors
for pressure injury development, provides an evaluation of the wound, recommends
wound cleansing procedures, performs pressure injury staging, and recommends
treatment interventions. METHODS: A mobile app was developed using a
contextualized instructional design, which involves a constructivist proposal and
planning, developing, and applying specific didactic situations, thus
incorporating mechanisms that favor contextualization. A literature search was
conducted to identify relevant studies for the construction of the mobile app.
The development process involved the selection of app tools, definition of the
navigation structure, and planning of the environment configuration. The
environment for downloading the app software on the Internet and installing it on
the mobile device was created. MAIN RESULTS: The literature search yielded 18
articles, 2 books, and 1 master's degree thesis. A mobile app was created with an
easy-to-use graphic interface. The app stores the patient's demographic
characteristics and provides an evaluation of his/her wound, a list of risk
factors for pressure injury development, wound cleansing procedures, and
treatment interventions. CONCLUSIONS: The developed app may be useful in clinical
practice, helping to prevent pressure injuries and promote select nursing
interventions for the treatment of patients with pressure injury.
PMID- 29346158
TI - Biomechanical Response to Osteoarthritis Pain Treatment May Impair Long-Term
Efficacy.
AB - Pain has an important physiologic role and acts with or stimulates motor system
adaptations to protect tissue from threats of damage. Although clinically
beneficial, removing the protective pain response may have negative consequence
in osteoarthritis, a mechanically mediated disease. We hypothesize motor system
adaptations to joint pain and its treatment may impact osteoarthritis
progression, thereby limiting efficacy of pain therapies.
PMID- 29346157
TI - Identifying Novel Signaling Pathways: An Exercise Scientists Guide to
Phosphoproteomics.
AB - We propose that phosphoproteomic-based studies will radically advance our
knowledge about exercise-regulated signaling events. However, these studies use
cutting-edge technologies that can be difficult for nonspecialists to understand.
Hence, this review is intended to help nonspecialists 1) understand the
fundamental technologies behind phosphoproteomic analysis and 2) use various
bioinformatic tools that can be used to interrogate phosphoproteomic datasets.
PMID- 29346159
TI - Making a Case for Cardiorespiratory Fitness Surveillance Among Children and
Youth.
AB - We review the evidence that supports cardiorespiratory fitness (CRF) as an
important indicator of current and future health among school-aged children and
youth, independent of physical activity levels. We discuss the merit of CRF
measurement for population health surveillance and propose the development of CRF
guidelines to help support regional, national, and international surveillance
efforts.
PMID- 29346160
TI - Potential Role of MicroRNA in the Anabolic Capacity of Skeletal Muscle With
Aging.
AB - Age-induced loss of skeletal muscle mass and function, termed sarcopenia, may be
the result of diminished response to anabolic stimulation. This review will
explore the hypothesis that alterations in the expression of microRNA with aging
contributes to reduced muscle plasticity resulting in impaired skeletal muscle
adaptations to exercise-induced anabolic stimulation.
PMID- 29346161
TI - Promotion of Exercise in Multiple Sclerosis Through Health Care Providers.
AB - Participation in exercise yields meaningful benefits among persons with multiple
sclerosis (MS), yet this population engages in low rates of health-promoting
physical activity. The disconnect between evidence of benefits and rates of
participation requires consideration of new opportunities for changing this
health behavior. The current article hypothesizes that the patient-provider
interaction offers a fertile opportunity for promoting exercise behavior in MS.
PMID- 29346162
TI - Specificity of "Live High-Train Low" Altitude Training on Exercise Performance.
AB - The novel hypothesis that "Live High-Train Low" (LHTL) does not improve sport
specific exercise performance (e.g., time trial) is discussed. Indeed, many
studies demonstrate improved performance after LHTL but, unfortunately, control
groups are often lacking, leaving open the possibility of training camp effects.
Importantly, when control groups, blinding procedures, and strict scientific
evaluation criteria are applied, LHTL has no detectable effect on performance.
PMID- 29346163
TI - The Hippo Signaling Pathway in the Regulation of Skeletal Muscle Mass and
Function.
AB - The Hippo signaling pathway regulates the activity of the proteins Yes-associated
protein (Yap) and transcriptional co-activator with PDZ-binding motif (Taz) to
control tissue growth in many different cell types. Previously, we demonstrated
that Yap is a critical regulator of skeletal muscle mass. We hypothesize that
alterations in Yap and Taz activity modulate the anabolic adaptations of skeletal
muscle to resistance exercise.
PMID- 29346164
TI - The Nuclear Receptor Nor-1 Is a Pleiotropic Regulator of Exercise-Induced
Adaptations.
AB - Exercise induces various physical and metabolic changes in skeletal muscle that
adaptively reprograms this tissue to current physiological and environmental
demands. Underlying these changes are broad modifications to gene expression. We
postulate that the nuclear hormone receptor, Nor-1, is activated after exercise,
and this transcription factor modifies gene expression to drive the molecular and
cellular adaptations associated with contractile reorganization.
PMID- 29346165
TI - Using Drosophila to Understand Biochemical and Behavioral Responses to Exercise.
AB - The development of endurance exercise paradigms in Drosophila has facilitated
study of genetic factors that control individual response to exercise. Recent
work in Drosophila has demonstrated that activation of octopaminergic neurons is
alone sufficient to confer exercise adaptations to sedentary flies. These results
suggest that adrenergic activity is both necessary and sufficient to promote
endurance exercise adaptations.
PMID- 29346166
TI - Cardiorespiratory Fitness in Children and Youth: A Call for Surveillance, But Now
How Do We Do It?
PMID- 29346167
TI - New Reference Values for Cardiopulmonary Exercise Testing in Children.
AB - INTRODUCTION: Cardiopulmonary exercise testing is an essential tool to assess
cardiorespiratory fitness (CRF) in children. There is a paucity of adequate
pediatric reference values that are independent of body size and pubertal stage.
The purpose of this study is to provide Z score equations for several maximal and
submaximal CRF parameters derived from a prospectively recruited sample of
healthy children. METHODS: In this cross-sectional multicenter study, we
prospectively recruited 228 healthy children 12 to 17 yr old in local schools. We
performed a symptom-limited cardiopulmonary exercise testing progressive ramp
protocol on an electronically braked cycle ergometer. Eighteen CRF parameters
were analyzed. We tested several regression models to obtain prediction curves
that minimized residual association with age, body size, and pubertal stage. Both
the predicted mean and the predicted SD were modeled to account for
heteroscedasticity. RESULTS: We identified nonlinear association of CRF
parameters with body size and significant heteroscedasticity. To normalize CRF
parameters, the use of a single body size variable was not sufficient. We
therefore used multivariable models with various combination of height, corrected
body mass, and age. Final prediction models yielded adjusted CRF parameters that
were independent of age, sex, body mass, height, body mass index, and Tanner
stages. CONCLUSIONS: We present Z score equations for several CRF parameters
derived from a healthy pediatric population. These reference values provide
updated predicted means and range of normality that are independent of sex and
body size. Further testing is needed to assess if these reference values increase
sensitivity and specificity to identify abnormal cardiorespiratory response in
children with chronic diseases.
PMID- 29346168
TI - A New Robot-assisted Billroth-I Reconstruction: Details of the Technique and
Early Results.
AB - BACKGROUND: Laparoscopic surgery for gastric tumor is considered a demanding
procedure because of lymph node dissection and reconstruction. Billroth-I (B-I)
reconstruction after laparoscopic distal gastrectomy is commonly performed
extracorporeally because of the complexity of an intracorporeal procedure.
Robotic surgery overcomes some limitations of laparoscopy, allowing to reproduce
the basic maneuvers of open surgery. We describe a new technique to perform
robotic B-I anastomosis. METHODS: Between January 2012 and February 2015, 5
patients underwent distal gastrectomy with intracorporeal B-I-stapled
anastomosis. Patient demographics, tumor characteristics, histopathologic
features, and perioperative data were analyzed. RESULTS: Median operative time
was 170 minutes (145 to 180 min). There were no conversions. Contrast swallow was
routinely performed on the third postoperative day. Median postoperative
hospitalization was 7 days (range: 6 to 8). No major complications or mortality
were observed. CONCLUSIONS: Robotic distal gastrectomy with intracorporeal B-I
anastomosis is a safe and promising technique in selected cases of gastric
tumors.
PMID- 29346169
TI - Sphenoid Dysplasia: A Rare Presentation of Infantile Myofibroma.
AB - The authors report a case of isolated congenital orbital myofibroma causing
sphenoid dysplasia and presenting as global restriction of extraocular motility
and ptosis in a neonate. Sphenoid wing dysplasia is most commonly associated
neurofibromatosis 1 but this patient had no evidence of neurofibromatosis on
clinical examination and genetic testing. Congenital orbital myofibroma can have
secondary effects on bone and likely the lesion was present early in development
leading to aplasia of the sphenoid bone. To the best of the authors' knowledge,
this is the first reported case of sphenoid wing aplasia secondary to congenital
orbital myofibroma independent of neurofibromatosis 1.
PMID- 29346170
TI - Apocrine Cystadenoma of the Eyelid: A Rare Palpebral Neoplasm. Report of 2 Cases.
AB - The authors report 2 cases of apocrine cystadenoma of the eyelid, 1 of which was
studied with immunohistochemical and other special stains. While a previous
report describes the tumor in a palpebro-orbital location, no other detailed
descriptions of a purely eyelid location are present in the literature. Apocrine
cystadenoma occupies an unusual portion of the spectrum of Moll gland tumors of
the eyelid. It has no definitive clinical characteristics and may be diagnosed
pathologically by hematoxylin-eosin-stained sections.
PMID- 29346171
TI - A Common Procedure With an Uncommon Pathology: Triamcinolone Acetonide Eyelid
Injection.
AB - Local corticosteroid injections are frequently employed by ophthalmologists to
treat a variety of ocular, periocular, and orbital inflammatory conditions.
Triamcinolone acetonide is a slowly dissolving crystalline corticosteroid that is
often used for this purpose because of its prolonged anti-inflammatory effect. On
occasion, previously injected corticosteroid material persists in tissues longer
than anticipated, creating nodules that may masquerade as other disease
conditions, or appearing incidentally in excised lesions on histopathologic
examination. The histopathologic features of corticosteroid residues are
unfamiliar to most ophthalmic pathologists and general pathologists. These
features are described herein. Triamcinolone acetonide deposits in the skin
appear as pale eosinophilic lakes of acellular frothy material on hematoxylin
eosin staining and are occasionally surrounded by a mild inflammatory reaction.
PMID- 29346172
TI - Apremilast Use in a Case of Cicatricial Ectropion Secondary to Severe Lamellar
Ichthyosis.
AB - Ichthyosis is a cutaneous disorder characterized by excessive amounts of dry
thickened skin surface scales. Ocular manifestations of ichthyosis include
cicatricial ectropion, which may cause exposure keratoconjunctivitis and rarely
corneal perforation. Topical emollients, anti-inflammatory ointments, and
systemic retinoids have been used to control the disease process, while surgical
correction with donor graft has been reserved for severe cases involving corneal
exposure. The authors report a case of a Caucasian male with lamellar ichthyosis
with severe bilateral upper and lower eyelid cicatricial ectropion and corneal
ulceration requiring surgical correction. Treatment with apremilast, a novel
phosphodiesterase-4 inhibitor, for the treatment of a concomitant plaque
psoriasis achieved good control of his skin diseases and minimized the recurrence
of eyelid ectropion.
PMID- 29346173
TI - The subresolution DaTSCAN phantom: a cost-effective, flexible alternative to
traditional phantom technology.
AB - The Alderson striatal phantom is frequently used to assess I-FP-CIT (Ioflupane)
image quality and to test semi-quantification software. However, its design is
associated with a number of limitations, in particular: unrealistic image
appearances and inflexibility. A new physical phantom approach is proposed on the
basis of subresolution phantom technology. The design incorporates thin slabs of
attenuating material generated through additive manufacturing, and paper sheets
with radioactive ink patterns printed on their surface, created with a
conventional inkjet printer. The paper sheets and attenuating slabs are
interleaved before scanning. Use of thin layers ensures that they cannot be
individually resolved on reconstructed images. An investigation was carried out
to demonstrate the performance of such a phantom in producing simplified I-FP-CIT
uptake patterns. Single photon emission computed tomography imaging was carried
out on an assembled phantom designed to mimic a healthy patient. Striatal binding
ratio results and linear striatal dimensions were calculated from the
reconstructed data and compared with that of 22 clinical patients without
evidence of Parkinsonian syndrome, determined from clinical follow-up. Striatal
binding ratio results for the fully assembled phantom were: 3.1, 3.3, 2.9 and 2.6
for the right caudate, left caudate, right putamen and right caudate,
respectively. All were within two SDs of results derived from a cohort of
clinical patients. Medial-lateral and anterior-posterior dimensions of the
simulated striata were also within the range of values seen in clinical data.
This work provides the foundation for the generation of a range of more
clinically realistic, physical phantoms.
PMID- 29346174
TI - Tonal and vowel information processing in Chinese spoken word recognition: an
event-related potential study.
AB - In the present study, the time course of tonal and vowel information processing
of the spoken words in Mandarin Chinese was investigated using a delayed-response
paradigm. Idiomatic materials, providing semantically highly constraining
contexts, were utilized. Besides being presented normally, the terminal
monosyllabic words in idioms were manipulated with Tonal, Vowel, or Triple
violations (i.e. with consonantal, tonal, and vowel mismatches). Event-related
potential results showed that all three violations elicited larger widespread
negativities in comparison with the Control condition, with the Triple violation
effect starting first from 150 ms, then the Vowel violation, and the Tonal
violation being the latest. The different starting times of the violation effects
suggest that the access of tonal information is slower than that of vowel
information, even though the lexical tones are very important in distinguishing
the meaning of Chinese words.
PMID- 29346175
TI - Long-Term Impacts Faced by Patients and Families After Harmful Healthcare Events.
AB - BACKGROUND: Patients and families report experiencing a multitude of harms from
medical errors resulting in physical, emotional, and financial hardships. Little
is known about the duration and nature of these harms and the type of support
needed to promote patient and family healing after such events. We sought to
describe the long-term impacts (LTIs) reported by patients and family members who
experienced harmful medical events 5 or more years ago. METHODS: We performed a
content analysis on 32 interviews originally conducted with 72 patients or family
members about their views of the factors contributing to their self-reported
harmful event. Interviews selected occurred 5 or more years after the harmful
event and were grouped by time since event, 5 to 9 years (22 interviews) or 10 or
more years (10 interviews) for analysis. We analyzed these interviews targeting
spontaneous references of ongoing impacts experienced by the participants.
RESULTS: Participants collectively described the following four LTIs:
psychological, social/behavioral, physical, and financial. Most cited
psychological impacts with half-reporting ongoing anger and vivid memories. More
than half reported ongoing physical impacts and one-third experienced ongoing
financial impacts. Long-term social and behavioral impacts such as alterations in
lifestyle, self-identity, and healthcare seeking behaviors were the most highly
reported. CONCLUSIONS: These patients and families experienced many profound LTIs
after their harmful medical event. For some, these impacts evolved into secondary
harms ongoing 10 years and more after the event. Our results draw attention to
the persistent impacts patients and families may experience long after harmful
events and the need for future research to understand and support affected
patients and families.
PMID- 29346176
TI - Rapid Response: To Scan or Not to Scan? The Utility of Noncontrast CT Head for
Altered Mental Status.
AB - OBJECTIVES: The aims of the study were the following: (1) to determine how often
computed tomography (CT) scans of the head are obtained on rapid responses called
for altered mental status (AMS), (2) to determine whether CT imaging of the head
is required during all rapid responses called for AMS, (3) to determine which
patients would benefit from CT scans of the head in this setting, (4) to note
whether an adequate neurologic exam was documented, (5) to determine the cost of
CT scans that did not change management, and (6) to examine the role of
medications leading to AMS. METHODS: The study was a retrospective chart review
at Abington Jefferson Hospital. Data collected included the age, sex, time of
rapid response, clinical condition of the patient, whether an arterial blood gas
and blood glucose were done, and whether a neurological exam was documented in
the resident's rapid response team note. The patient's medications were also
reviewed. Computed tomography scan findings as well as changes made in a
patient's care as a result of the scan were recorded. Any findings that did not
lead to a change in management were considered a "negative" scan. RESULTS:
Overall, 610 rapid responses were activated from January to August 2016. One
hundred four (17.04%) of the total rapid responses were for AMS and 83 (79.8%) of
these patients underwent noncontrast CT scan of the head. The mean (SD) age of
the patients was 74.7 (13.6) years. A total of 56.6% were female. The most
frequent clinical conditions documented at the time of rapid responses were noted
as confused (33.7%, 28/83), either lethargic or unconscious (32.5%, 27/83), and
concern for stroke (21.7%, 18/83). A total of 96.4% (80/83) of the CT scans done
were negative for any acute changes. The three patients with positive scans
(3/83) had a change in management as a result of the scans. If patients with
symptoms concerning for stroke and unconscious patients are excluded, the total
number of remaining patients is 56. Of these, zero patients had a positive scan.
A total of 64.7% of the rapid response teams were activated either in the
afternoon (31.3%) or at night (33.7%). A total of 33.7% had a complete
neurological exam documented. A total of 66.2% were either incomplete (34.9%) or
absent (31.3%). Sixty percent of the patients who had a CT head for AMS also had
a blood sugar checked at bedside. Thirty-eight percent had an arterial blood gas.
More than half the patients were taking one or more sedating medications (45/83,
57.8%). Most patients were not on anticoagulants (79.5%). CONCLUSIONS: The
findings of this study suggest that CT scan of the head is useful in older
patients, patients with symptoms concerning for stroke, or cases of sudden onset
of impaired consciousness. Noncontrast CT scans of the head are not useful for
other presentations of AMS.
PMID- 29346177
TI - No association between FOXP2 rs10447760 and schizophrenia in a replication study
of the Chinese Han population.
AB - BACKGROUND: Schizophrenia (SCZ) is a severe and heritable psychiatric disorder,
and previous studies have shown that regulation of the forkhead-box P2 gene
(FOXP2) may play a role in schizophrenia. Moreover, just a few studies have
identified a single nucleotide polymorphism (SNP) rs10447760 within the gene that
was a risk variant for SCZ in the Chinese Han population. METHODS: To examine
whether the variant in the FOXP2 gene contributes toward SCZ susceptibility, we
carried out an association analysis of the SNP rs10447760 of the FOXP2 gene in a
case-control study (1405 cases, 1137 controls) from China. RESULTS: We identified
no association of rs10447760 in the FOXP2 gene with SCZ (all P>0.05). In
addition, a meta-analysis indicated that the SNP rs10447760 was not associated
with susceptibility to SCZ in Han Chinese populations (pooled odds ratio=1.44,
95% confidence interval: 0.63-3.31, P=0.39). CONCLUSION: Thus, our results did
not support the association between FOXP2 rs10447760 and schizophrenia in a
Chinese Han population, and large-scale genetic replication studies with
different racial and geographic origins are required in the future.
PMID- 29346178
TI - Multiple primary malignancies and prolonged survival in a patient with widespread
metastatic cutaneous melanoma.
PMID- 29346179
TI - Avstick: An Intravenous Catheter Insertion Simulator for Use with Standardized
Patients.
AB - An overwhelming majority of hospitalized patients undergo intravenous (IV)
catheter insertion in order to receive hydration and necessary medication.
Current IV insertion training techniques include manikins that are unable to
react or give feedback to the trainee. The Avstick(r) is a realistic training
device that can be worn by an actor, allowing a nurse trainee to perform an IV
catheter insertion on a live patient without causing the person harm. The purpose
of this study is to demonstrate the effectiveness of the Avstick in nursing
education to increase nurse-patient communication and trainee self-efficacy.
PMID- 29346180
TI - Development of a PD-L1 Complementary Diagnostic Immunohistochemistry Assay
(SP142) for Atezolizumab.
AB - Cancer immunotherapies, such as atezolizumab, are proving to be a valuable
therapeutic strategy across indications, including non-small cell lung cancer
(NSCLC) and urothelial cancer (UC). Here, we describe a diagnostic assay that
measures programmed-death ligand 1 (PD-L1) expression, via immunohistochemistry,
to identify patients who will derive the most benefit from treatment with
atezolizumab, a humanized monoclonal anti-PD-L1 antibody. We describe the
performance of the VENTANA PD-L1 (SP142) Assay in terms of specificity,
sensitivity, and the ability to stain both tumor cells (TC) and tumor
infiltrating immune cells (IC), in NSCLC and UC tissues. The reader precision,
repeatability and intermediate precision, interlaboratory reproducibility, and
the effectiveness of pathologist training on the assessment of PD-L1 staining on
both TC and IC were evaluated. We detail the analytical validation of the VENTANA
PD-L1 (SP142) Assay for PD-L1 expression in NSCLC and UC tissues and show that
the assay reliably evaluated staining on both TC and IC across multiple
expression levels/clinical cut-offs. The reader precision showed high overall
agreement when compared with consensus scores. In addition, pathologists met the
predefined training criteria (>=85.0% overall percent agreement) for the
assessment of PD-L1 expression in NSCLC and UC tissues with an average overall
percent agreement >=95.0%. The assay evaluates PD-L1 staining on both cell types
and is robust and precise. In addition, it can help to identify those patients
who may benefit the most from treatment with atezolizumab, although treatment
benefit has been demonstrated in an all-comer NSCLC and UC patient
population.This is an open-access article distributed under the terms of the
Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC
ND), where it is permissible to download and share the work provided it is
properly cited. The work cannot be changed in any way or used commercially
without permission from the journal. http://creativecommons.org/licenses/by-nc
nd/4.0/.
PMID- 29346181
TI - 34BetaE12 and Alfa-Methylacyl Coenzyme A Racemase (AMACR) Antibodies Better Than
p63 Antibody Distinguish Normal and Neoplastic Glands in Prostatic Tissue With
Thermal Artifacts.
AB - The occurrence of inked margins with crush artifact derived from the
electrocauterization in radical prostatectomy and/or the presence of crushed
areas with distorted glands in prostatic samples after transurethral resection of
prostate (TURP) can induce a significant interobserver variability during
histopathologic evaluation of specimens. The specific immunostaining for basal
cell markers 34BetaE12 and p63 and for alfa-methylacyl coenzyme A racemase
(AMACR) in neoplastic cells is commonly used as an ancillary tool to establish
benign and malignant glands. In this study we carried out the immunohistochemical
reactions for p63, 34BetaE12, and AMACR on 3 different and successive paraffin
sections to discriminate malignant and benign prostatic glands, distorted and
crushed by the thermal artifacts in 60 radical prostatectomies and 50 TURP
samples. All prostatic acinar adenocarcinoma showed the loss of basal cell
markers and expression of AMACR, whereas p63 failed to stain the basal cell layer
in benign crushed prostatic glands. The same cauterized glands were steadily
positive for 34BetaE12. The high percentage of p63 false negative cases in benign
distorted and crushed glands could be explained by the thermal artifacts which
might cause lack of p63 antigenicity. In contrast, the antigenicity of 34BetaE12
and AMACR seem not to be affected by cautery artifacts. Thus, in cauterized
suspicious prostatic glands an immunohistochemistry panel including, p63,
34BetaE12, and AMACR or only 34BetaE12 is recommended. In addition, after the
first evaluation with only p63, we suggest that a separate and confirmatory
staining for 34BetaE12 is strongly recommended.
PMID- 29346182
TI - Atypical Teratoid Rhabdoid Tumor of the Cauda Equina in a Child: Report of a Very
Unusual Case.
AB - Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive malignant
primitive neoplasms that commonly occur in children younger than 2 years of age.
The prognosis is generally dismal with a median survival time of <1 year. The
majority of AT/RT occur in the posterior fossa and less frequently the
supratentorium. Primary pediatric spinal AT/RT are exceedingly rare and only 15
cases have been reported to date. Here we report a very unusual case of primary
spinal AT/RT extensively involving the spinal cord from T11 down to the cauda
equina. In this patient, the tumor was highly aggressive and resulted in
extensive dissemination into the nerve roots and paraspinal soft tissue rapidly
resulting in the patient's death 1 month after diagnosis. to the best of our
knowledge, this degree of involvement of the spine by a primary AT/RT has not
been described before.
PMID- 29346183
TI - Near-infrared spectroscopy to predict organ failure and outcome in sepsis: the
Assessing Risk in Sepsis using a Tissue Oxygen Saturation (ARISTOS) study.
AB - OBJECTIVES: Sepsis is acute organ dysfunction in the setting of infection. An
accurate diagnosis is important to guide treatment and disposition. Tissue oxygen
saturation (StO2) can be estimated noninvasively by near-infrared spectroscopy
(NIRS), and may be an indicator of microcirculatory dysfunction in early sepsis.
We aimed to determine the utility of StO2 for sepsis recognition and outcome
prediction among patients presenting to the emergency department (ED) with
infection. PATIENTS AND METHODS: A multicentre, prospective, observational cohort
study recruited patients who were being admitted to hospital with infection. StO2
was measured in the ED using a handheld NIRS device, Inspectra 300. Outcomes were
sepsis, defined as an increase in sequential organ failure assessment score of at
least 2 points within 72 h, and composite in-hospital mortality/ICU admission at
least 3 days. RESULTS: A cohort of 323 participants, median age 64 (interquartile
range: 47-77) years, was recruited at three Australian hospitals. 143 (44%)
fulfilled the criteria for sepsis and 22 (7%) died within 30 days. The mean+/-SD
StO2 was 74+/-8% in sepsis and 78+/-7% in nonsepsis (P<0.0001). StO2 correlated
with the peak sequential organ failure assessment score (Spearman's rho -0.27,
P<0.0001). Area under the receiver operating characteristic curve was 0.66 (95%
confidence interval: 0.60-0.72) for sepsis and 0.66 (0.58-0.75) for the composite
outcome. StO2 less than 75% had an odds ratio of 2.67 (1.45-4.94; P=0.002), for
the composite outcome compared with StO2 at least 75%. CONCLUSION: NIRS-derived
StO2 correlates with organ failure and is associated with outcome in sepsis.
However, its ability to differentiate sepsis among ED patients with infection is
limited. NIRS cannot be recommended for this purpose.
PMID- 29346184
TI - Synergistic Impact of Training Followed by On-Site Support on HIV Clinical
Practice: A Mixed-Design Study in Uganda With Pre/Post and Cluster-Randomized
Trial Components.
AB - BACKGROUND: Task shifting can expand antiretroviral therapy access, but little is
known about effective approaches to improve clinical practice among midlevel
practitioners (MLPs) such as clinical officers, nurses, and midwives. The
Integrated Infectious Diseases Capacity Building Evaluation compared training
alone with training combined with on-site support (OSS). METHODS: Two MLPs each
from 36 health facilities attended the 5-week Integrated Management of Infectious
Disease training. After training, 18 facilities randomly assigned to arm A
received OSS for 9 months, whereas 18 arm B facilities did not. Clinical faculty
assessed MLP HIV clinical practice on 6 tasks: history taking, physical
examination, laboratory investigations, diagnosis, treatment, and patient
education. We analyzed the effect of training alone and training combined with
OSS as the pre/post change within each arm. We analyzed the incremental effect of
OSS with a difference-in-difference analysis that compared changes between arms.
RESULTS: Training alone and training combined with OSS significantly improved
clinical practice in patient history taking (13% and 24% increase, respectively),
physical examination (54% and 71%), laboratory investigations (32% and 20%), and
diagnosis (31% and 51%). Combined training and OSS also improved patient
education significantly (72% increase). Effect sizes for training combined with
OSS were larger than for training alone except for laboratory investigations, and
the effects were robust in sensitivity analyses. The incremental effect of OSS on
diagnosis was significant [adjusted relative risk = 1.23; 95% confidence interval
= 1.00 to 1.50]. CONCLUSIONS: Combined training and OSS improved MLP HIV clinical
practice over training alone and can contribute to continued expansion of access
to antiretroviral therapy.
PMID- 29346185
TI - Brief Report: Higher ART Adherence Is Associated With Lower Systemic Inflammation
in Treatment-Naive Ugandans Who Achieve Virologic Suppression.
AB - BACKGROUND: Residual systemic inflammation persists despite suppressive
antiretroviral therapy (ART) and is associated with non-AIDS clinical outcomes.
We aimed to evaluate the association between ART adherence and inflammation in
Ugandans living with HIV who were predominantly receiving nevirapine-based ART
with a thymidine analog backbone and were virologically suppressed by
conventional assays. METHODS: Plasma concentrations of interleukin-6 (IL-6), D
dimer, soluble (s)CD14, sCD163, and the kynurenine/tryptophan ratio, in addition
to CD8 T-cell activation, were measured at baseline and 6 months after ART
initiation in treatment-naive adults who achieved an undetectable plasma HIV RNA
(<400 copies/mL) at their 6-month visit. Adherence was measured through
medication event monitoring system and calculated as the ratio of
observed/prescribed device openings per participant. We fit adjusted linear
regression models to estimate the association between ART adherence and the log
transformed plasma concentrations of inflammatory biomarkers. RESULTS: We
evaluated 282 participants (median age, 35 years; 70% women). The median
(interquartile range) adherence was 93% (84-98). In the adjusted analyses, for
every 10% increase in average ART adherence, we found a 15% [P < 0.0001; 95%
confidence interval (CI), -21.0 to -7.9], 11% (P = 0.017; 95% CI, -18.3 to -2.0),
and 3% (P = 0.028; 95% CI, -5.0 to -0.3) decrease in IL-6, D-dimer, and sCD14,
respectively. CONCLUSIONS: Higher ART adherence was associated with lower levels
of biomarkers of inflammation, immune activation, and coagulopathy among Ugandans
living with HIV who achieved viral suppression shortly after ART initiation. This
suggests that ART adherence could have biological consequences beyond viral
suppression. Whether ART adherence optimization in virologically suppressed
individuals could reduce residual inflammation remains unknown.
PMID- 29346186
TI - Fall Rates in Urban and Rural Nursing Units: Does Location Matter?
AB - Patient falls remain a leading adverse event in hospitals. In a study of 65 rural
hospitals with 222 nursing units and 560 urban hospitals with 4274 nursing units,
we found that geographic region, unit type, and nurse staffing, education,
experience, and outcomes were associated with fall rates. Implications include
specific attention to fall prevention in rehabilitation units, creating better
work environments that promote nurse retention, and provide RN-BSN educational
opportunities.
PMID- 29346187
TI - Quality in Postoperative Patient Handover: Different Perceptions of Quality
Between Transferring and Receiving Nurses.
AB - BACKGROUND: A safe and efficient patient handover is important to ensure high
quality patient care and reduce the risk of patient harm. Few studies have
explored handover activities beyond information transfer. PURPOSE: The aims were
to assess overall postoperative handover quality and relate quality assessments
to handover circumstances, conduct, and teamwork and to compare transferring and
receiving nurses' evaluations of handover quality. METHOD: This was a cross
sectional study using the Norwegian Handover Quality Rating Form (N-HQRF). In
addition, data were collected on nurses' evaluations of the patient condition,
handover preparation, and participating nurses' clinical experience. RESULTS:
Although total perceived handover quality was high in a large majority of cases,
there were significant differences between transferring and receiving nurses'
evaluations of the same handover. Lower-quality handovers had a higher frequency
of time pressure, uncertainty, and patient-related problems. CONCLUSION: The
findings point to the need to assess handover quality in a wider perspective.
Handover circumstances might impact handover quality and should be considered
when procedures for handover quality are designed and implemented.
PMID- 29346188
TI - Evaluation of Role Acquisition and Preparation for the CNL Certification
Examination Through an Online Immersion Course.
PMID- 29346190
TI - Why Don't Hospitals Prioritize Substance Abuse in Their Community Benefit
Programming?
AB - The goal of this study was to understand whether Appalachian Ohio hospitals
prioritized substance abuse in their IRS-mandated community health needs
assessments (CHNAs) and if not, what factors were important in this decision.
Analysis of CHNA reports from all 28 hospitals in the region supplemented
interview data from in-depth phone interviews, with 17 participants tasked with
overseeing CHNAs at 21 hospitals. The CHNA reports show that hospitals in this
region prioritize substance abuse and mental health less often than access to
care and obesity. Interviews suggest 4 reasons: lack of resources, risk aversion,
concern about hospital expertise, and stigma related to substance abuse.
Hospitals are playing a larger role in public health as a result of CHNA
requirements but resist taking on challenging problems such as substance abuse.
The report concludes by summarizing concrete steps to ensure that community
benefit efforts address pressing health problems. The implications of this study
are manifest in concrete recommendations for encouraging hospitals to address
pressing health problems in their community benefit efforts.
PMID- 29346191
TI - The Four Corners Sign: A Specific Imaging Feature in Differentiating Systemic
Sclerosis-related Interstitial Lung Disease From Idiopathic Pulmonary Fibrosis.
AB - PURPOSE: Differentiating between systemic sclerosis-related interstitial lung
disease (SSc-ILD) and idiopathic pulmonary fibrosis (IPF) is important because of
the differences in workup, prognosis, and treatment. However, there is much
overlap in the appearance of these 2 entities on high-resolution computed
tomography. We propose that inflammation and/or fibrosis focally or
disproportionately involving the bilateral anterolateral upper lobes and
posterosuperior lower lobes ["Four Corners" Sign (FCS)] is specific for SSc-ILD.
MATERIALS AND METHODS: Randomized high-resolution computed tomography studies
from 74 IPF and 73 SSc-ILD cases were evaluated by 2 thoracic radiologists
blinded to all patient data. For each case the reviewers noted whether the FCS
was present and assigned a confidence level on the basis of a 7-point Likert
scale. The same process was then performed on a randomized external validation
group of 42 SSc-ILD and 42 IPF cases. RESULTS: For Likert scores of 6 or 7
("mostly agree" or "entirely agree" that the FCS is present, respectively) the
sensitivity in SSc was 16.4% (95% confidence interval, 9.7%, 26.6%), specificity
100.0% (95% confidence interval, 95.1%, 100.0%). There was a significant
association between a confidently present FCS and SSc compared with a confidently
present FCS and IPF (P=0.0003). Analysis on an external validation group of 42
SSc and 42 IPF cases conferred similarly high specificity for SSc in cases
characterized as FCS with high confidence. CONCLUSION: The FCS, a pattern of
focal or disproportionate inflammation and/or fibrosis involving the bilateral
anterolateral upper lobes and posterosuperior lower lobes, is specific for SSc
ILD when readers are confident of its presence.
PMID- 29346189
TI - The Impact of Implementing Tobacco Control Policies: The 2017 Tobacco Control
Policy Scorecard.
AB - The Tobacco Control Scorecard, published in 2004, presented estimates of the
effectiveness of different policies on smoking rates. Since its publication, new
evidence has emerged. We update the Scorecard to include recent studies of demand
reducing tobacco policies for high-income countries. We include cigarette taxes,
smoke-free air laws, media campaigns, comprehensive tobacco control programs,
marketing bans, health warnings, and cessation treatment policies. To update the
2004 Scorecard, a narrative review was conducted on reviews and studies published
after 2000, with additional focus on 3 policies in which previous evidence was
limited: tobacco control programs, graphic health warnings, and marketing bans.
We consider evaluation studies that measured the effects of policies on smoking
behaviors. Based on these findings, we derive estimates of short-term and long
term policy effect sizes. Cigarette taxes, smoke-free air laws, marketing
restrictions, and comprehensive tobacco control programs are each found to play
important roles in reducing smoking prevalence. Cessation treatment policies and
graphic health warnings also reduce smoking and, when combined with policies that
increase quit attempts, can improve quit success. The effect sizes are broadly
consistent with those previously reported for the 2004 Scorecard but now reflect
the larger evidence base evaluating the impact of health warnings and advertising
restrictions.
PMID- 29346192
TI - Image Quality, Overall Evaluability, and Effective Radiation Dose of Coronary
Computed Tomography Angiography With Prospective Electrocardiographic Triggering
Plus Intracycle Motion Correction Algorithm in Patients With a Heart Rate Over 65
Beats Per Minute.
AB - PURPOSE: Recently, a new intracycle motion correction algorithm (MCA) was
introduced to reduce motion artifacts from heart rate (HR) in coronary computed
tomography angiography (cCTA). The aim of the study was to evaluate the image
quality, overall evaluability, and effective radiation dose (ED) of cCTA with
prospective electrocardiographic (ECG) triggering plus MCA as compared with
standard protocol with retrospective ECG triggering in patients with HR>=65 bpm.
MATERIALS AND METHODS: One hundred consecutive patients (67+/-10 y) scheduled for
cCTA with 65
= 30. In
research-related hypothesis testing, the term "statistically significant" is used
to describe when an observed difference or association has met a certain
threshold. This significance threshold or cut-point is denoted as alpha (alpha)
and is typically set at .05. When the observed P value is less than alpha, one
rejects the null hypothesis (Ho) and accepts the alternative. Clinical
significance is even more important than statistical significance, so treatment
effect estimates and confidence intervals should be regularly reported. A type I
error occurs when the Ho of no difference or no association is rejected, when in
fact the Ho is true. A type II error occurs when the Ho is not rejected, when in
fact there is a true population effect. Power is the probability of detecting a
true difference, effect, or association if it truly exists. Sample size
justification and power analysis are key elements of a study design. Ethical
concerns arise when studies are poorly planned or underpowered. When calculating
sample size for comparing groups, 4 quantities are needed: alpha, type II error,
the difference or effect of interest, and the estimated variability of the
outcome variable. Sample size increases for increasing variability and power, and
for decreasing alpha and decreasing difference to detect. Sample size for a given
relative reduction in proportions depends heavily on the proportion in the
control group itself, and increases as the proportion decreases. Sample size for
single-group studies estimating an unknown parameter is based on the desired
precision of the estimate. Interim analyses assessing for efficacy and/or
futility are great tools to save time and money, as well as allow science to
progress faster, but are only 1 component considered when a decision to stop or
continue a trial is made.
PMID- 29346211
TI - Intratidal Analysis of Intraoperative Respiratory System Mechanics.
PMID- 29346212
TI - Intratidal Analysis of Intraoperative Respiratory System Mechanics: Keep it
Simple.
PMID- 29346213
TI - Self-Esteem and Anger in Borderline Patients With Self-Injury Behavior.
AB - Anger and low self-esteem characterize borderline individuals, yet little is
known about their role and impact in the presence or absence of self-injury
behavior. The present study aimed to investigate the impact of anger and self
esteem in borderline patients and whether these variables distinguish these
patients with and without self-injury. Patients were recruited from a psychiatric
service and were evaluated for self-esteem and anger. Additionally, impulsivity
and symptoms were assessed. Two groups were compared, one with self-injurious
behavior (n = 18) and another one without it (n = 23). Those who injure
themselves seem to have a lower self-esteem (p < 0.001), yet the strengthening of
self-esteem seems to have different outcomes, according to the presence or
absence of self-injury. Anger and self-esteem seem to influence the severity of
diagnosis, but only in patients who self-injure. Anger and self-esteem may
influence borderline patients differently according to the presence or absence of
self-injury.
PMID- 29346214
TI - Validation of Biomarkers for Early Detection of Pancreatic Cancer: Summary of The
Alliance of Pancreatic Cancer Consortia for Biomarkers for Early Detection
Workshop.
AB - Pancreatic cancer is the third leading cause of cancer death in the United
States, and the 5-year relative survival for patients diagnosed with pancreatic
cancer is less than 10%. Early intervention is the key to a better survival
outcome. Currently, there are no biomarkers that can reliably detect pancreatic
cancer at an early stage or identify precursors that are destined to progress to
malignancy. The National Cancer Institute in partnership with the Kenner Family
Research Fund and the Pancreatic Cancer Action Network convened a Data Jamboree
on Biomarkers workshop on December 5, 2016, to discuss and evaluate existing or
newly developed biomarkers and imaging methods for early detection of pancreatic
cancer. The primary goal of this workshop was to determine if there are any
promising biomarkers for early detection of pancreatic cancer that are ready for
clinical validation. The Alliance of Pancreatic Cancer Consortia for Biomarkers
for Early Detection, formed under the auspices of this workshop, will provide the
common platform and the resources necessary for validation. Although none of the
biomarkers evaluated seemed ready for a large-scale biomarker validation trial, a
number of them had sufficiently high sensitivity and specificity to warrant
additional research, especially if combined with other biomarkers to form a
panel.
PMID- 29346215
TI - Challenges and Perspectives for Immunotherapy in Adenocarcinoma of the Pancreas:
The Cancer Immunity Cycle.
AB - Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a devastating 5
year overall survival of only approximately 7%. Although just 4% of all malignant
diseases are accounted to PDAC, it will become the second leading cause of cancer
related deaths before 2030. Immunotherapy has proven to be a promising
therapeutic option in various malignancies such as melanoma, non-small cell lung
cancer (NSCLC), microsatellite instability-high gastrointestinal cancer, urinary
tract cancer, kidney cancer, and others. In this review, we summarize recent
findings about immunological aspects of PDAC with the focus on the proposed model
of the "cancer immunity cycle". By this model, a deeper understanding of the
underlying mechanism in achieving a T-cell response against cancer cells is
provided. There is currently great interest in the field around designing novel
immunotherapy combination studies for PDAC based on a sound understanding of the
underlying immunobiology.
PMID- 29346217
TI - Pathological and Molecular Aspects to Improve Endoscopic Ultrasonography-Guided
Fine-Needle Aspiration From Solid Pancreatic Lesions.
AB - Endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has been
applied to pancreatic lesions since the 1990s, and its use is now widespread.
Improvements in endoscopic devices and sampling techniques have resulted in
excellent diagnostic ability for solid pancreatic lesions. However, clinical
improvements alone are not responsible for it; pathological aspects have also
played important roles. Rapid on-site evaluation minimizes endoscopic procedures,
although its value at improving the diagnostic ratio is still debated. Diagnostic
efficacy differs by sample preparations (direct smear, cytospin, liquid-based
cytology, cell block, and biopsy) and by staining methods (Papanicoloau, Diff
Quik, hematoxylin-eosin, and Giemsa). Several immunocytochemistry protocols aid
in diagnosing epithelial components with cytological atypia and in
differentiating various tumor types. One cytopathology diagnostic system is
telecytology, which uses transmitted digital images and enables real-time
diagnosis of EUS-FNA samples by expert cytologists at remote locations. However,
EUS-FNA samples are useful for more than just diagnoses, as molecular analysis of
these samples allows the identification of prognostic markers, such as genetic
alterations in K-ras and EGFR. Expression of drug-metabolizing enzymes, human
equilibrative nucleoside transporter 1, correlates with the response to
gemcitabine-based chemotherapy. These pathology efforts have enhanced the
diagnostic efficacy of EUS-FNA, thereby leading to better outcomes for patients
with pancreatic diseases.
PMID- 29346216
TI - Obesity and Pancreatic Cancer: Overview of Epidemiology and Potential Prevention
by Weight Loss.
AB - Currently, there are no effective preventive strategies for pancreatic cancer.
Obesity has been increasingly recognized as a strong but modifiable risk factor
of pancreatic cancer. In this article, we aim to review the literature regarding
weight loss on prevention of pancreatic cancer. Epidemiological and laboratory
studies have shown that obesity is associated with increased incidence of
pancreatic cancer and potentially worse cancer outcome. Whereas the underlying
pathomechanisms remain unclear, chronic inflammation, insulin resistance, and
altered intestinal microbiota are all implicated in the carcinogenic effect of
obesity. Weight loss, especially the durable and significant weight loss after
bariatric surgery, has been shown to reduce the risks of multiple cancers and may
become a good intervention for pancreatic cancer prevention.
PMID- 29346218
TI - Predicting Pancreatitis Phenotype Based on a Shared Genotype.
PMID- 29346219
TI - Pancreatic Metastases as the Initial Manifestation of a Neuroendocrine Carcinoma
of the Uterine Cervix.
PMID- 29346220
TI - TRO40303 Ameliorates Alcohol-Induced Pancreatitis Through Reduction of Fatty Acid
Ethyl Ester-Induced Mitochondrial Injury and Necrotic Cell Death: Erratum.
PMID- 29346221
TI - A Validation Argument for a Simulation-Based Training Course Centered on
Assessment, Recognition, and Early Management of Pediatric Sepsis.
AB - INTRODUCTION: Early recognition of sepsis remains one of the greatest challenges
in medicine. Novice clinicians are often responsible for the recognition of
sepsis and the initiation of urgent management. The aim of this study was to
create a validity argument for the use of a simulation-based training course
centered on assessment, recognition, and early management of sepsis in a
laboratory-based setting. METHODS: Five unique simulation scenarios were
developed integrating critical sepsis cues identified through qualitative
interviewing. Scenarios were piloted with groups of novice, intermediate, and
expert pediatric physicians. The primary outcome was physician recognition of
sepsis, measured with an adapted situation awareness global assessment tool.
Secondary outcomes were physician compliance with pediatric advanced life support
(PALS) guidelines and early sepsis management (ESM) recommendations, measured by
two internally derived tools. Analysis compared recognition of sepsis by levels
of expertise and measured association of sepsis recognition with the secondary
outcomes. RESULTS: Eighteen physicians were recruited, six per study group. Each
physician completed three sepsis simulations. Sepsis was recognized in 19 (35%)
of 54 simulations. The odds that experts recognized sepsis was 2.6 [95%
confidence interval (CI) = 0.5-13.8] times greater than novices. Adjusted for
severity, for every point increase in the PALS global performance score, the odds
that sepsis was recognized increased by 11.3 (95% CI = 3.1-41.4). Similarly, the
odds ratio for the PALS checklist score was 1.5 (95% CI = 0.8-2.6). Adjusted for
severity and level of expertise, the odds of recognizing sepsis was associated
with an increase in the ESM checklist score of 1.8 (95% CI = 0.9-3.6) and an
increase in ESM global performance score of 4.1 (95% CI = 1.7-10.0). CONCLUSIONS:
Although incomplete, evidence from initial testing suggests that the simulations
of pediatric sepsis were sufficiently valid to justify their use in training
novice pediatric physicians in the assessment, recognition, and management of
pediatric sepsis.
PMID- 29346222
TI - "To Err Is Human" but Disclosure Must be Taught: A Simulation-Based Assessment
Study.
AB - INTRODUCTION: Although error disclosure is critical in promoting safety and
patient-centered care, physicians are inconsistently trained in its practice, and
few objective methods to assess competence exist. We used an immersive simulation
scenario to determine whether providers with varying levels of clinical
experience adhere to the disclosure safe practice guidelines when exposed to a
serious adverse event simulation scenario. METHODS: This was a prospective cohort
study with medical students, junior emergency medicine (EM) residents (PGY 1-2),
senior EM residents (PGY 3-4), and attending EM physicians participating in a
simulated case in which a scripted medication overdose resulted in an adverse
event. Each scenario was videotaped and scored by two expert raters based on a 6
component, 21-point disclosure assessment instrument. RESULTS: There were 12
participants in each study group (N = 48). There was good interrater reliability
(kappa = 0.70). Total scores improved significantly as the level of training
increased: medical student = 10.3 (2.7), PGY 1-2 = 12.3 (6.2), PGY 3-4 = 13.7
(3.2), and attending physicians = 12.8 (3.7) (P = 0.03). Seventy-five percent of
participants did not address preventing recurrence of the error. Fifty-six
percent offered no apology or only offered it with prompting from the patient;
only 23% offered an apology with the initial disclosure. CONCLUSIONS: We
demonstrated suboptimal adherence to best practices guidelines for error
disclosure when providers are assessed in an immersive simulation setting.
Despite a correlation in performance of medical error disclosure with increased
physician experience, this study suggests that healthcare providers may need
additional training to comply with safe practice guidelines for disclosure of
unanticipated adverse events.
PMID- 29346223
TI - Learner-Adaptive Educational Technology for Simulation in Healthcare: Foundations
and Opportunities.
AB - STATEMENT: Despite evidence that learners vary greatly in their learning needs,
practical constraints tend to favor ''one-size-fits-all'' educational approaches,
in simulation-based education as elsewhere. Adaptive educational technologies -
devices and/or software applications that capture and analyze relevant data about
learners to select and present individually tailored learning stimuli - are a
promising aid in learners' and educators' efforts to provide learning experiences
that meet individual needs. In this article, we summarize and build upon the 2017
Society for Simulation in Healthcare Research Summit panel discussion on adaptive
learning. First, we consider the role of adaptivity in learning broadly. We then
outline the basic functions that adaptive learning technologies must implement
and the unique affordances and challenges of technology-based approaches for
those functions, sharing an illustrative example from healthcare simulation.
Finally, we consider future directions for accelerating research, development,
and deployment of effective adaptive educational technology and techniques in
healthcare simulation.
PMID- 29346224
TI - Tipping the Scales: Prioritizing Mentorship and Support in Simulation Faculty
Development.
PMID- 29346225
TI - Validating Lung Models Using the ASL 5000 Breathing Simulator.
AB - OBJECTIVE: This study sought to validate pediatric models with normal and altered
pulmonary mechanics. METHODS: PubMed and CINAHL databases were searched for
studies directly measuring pulmonary mechanics of healthy infants and children,
infants with severe bronchopulmonary dysplasia and neuromuscular disease. The ASL
5000 was used to construct models using tidal volume (VT), inspiratory time (TI),
respiratory rate, resistance, compliance, and esophageal pressure gleaned from
literature. Data were collected for a 1-minute period and repeated three times
for each model. t tests compared modeled data with data abstracted from the
literature. Repeated measures analyses evaluated model performance over multiple
iterations. Statistical significance was established at a P value of less than
0.05. RESULTS: Maximum differences of means (experimental iteration mean -
clinical standard mean) for TI and VT are the following: term infant without lung
disease (TI = 0.09 s, VT = 0.29 mL), severe bronchopulmonary dysplasia (TI = 0.08
s, VT = 0.17 mL), child without lung disease (TI = 0.10 s, VT = 0.17 mL), and
child with neuromuscular disease (TI = 0.09 s, VT = 0.57 mL). One-sample testing
demonstrated statistically significant differences between clinical controls and
VT and TI values produced by the ASL 5000 for each iteration and model (P <
0.01). The greatest magnitude of differences was negligible (VT < 1.6%, TI = 18%)
and not clinically relevant. CONCLUSIONS: Inconsistencies occurred with the
models constructed on the ASL 5000. It was deemed accurate for the study
purposes. It is therefore essential to test models and evaluate magnitude of
differences before use.
PMID- 29346226
TI - Preparing Physiotherapy Students for Clinical Placement: Student Perceptions of
Low-Cost Peer Simulation. A Mixed-Methods Study.
AB - INTRODUCTION: Simulation is increasingly used in health care education, yet the
organizational and financial costs can be prohibitive. This study aimed to
investigate whether peer simulation is perceived by third-year undergraduate
physiotherapy students as valuable for clinical placement preparation. METHODS:
Third-year undergraduate physiotherapy students participated in a 9-week peer
simulation program, using each other as patients, and were invited to complete
two surveys evaluating perceptions of the program. The program consisted of
weekly patient interactions during which students were required to assess and
treat a "patient" under strict simulation guidelines and in accordance with
stated learning objectives. Items rated included self-perceived skills,
confidence, time management, and clinical placement readiness and included
collection of qualitative responses. Surveys were released at commencement and
completion of the simulation program. RESULTS: Of 79 third-year students, 63%
completed survey 1 and 66% completed survey 2. Students had high expectations of
the program and these were consistently met. Peer simulation rated highly for all
items, including identifying knowledge and skill deficits, and improving
confidence, clinical reasoning, time management, and communication. Simulation
was considered safe, supportive, engaging, and valuable for clinical placement
preparation. Students identified some lack of authenticity when working with
peers. CONCLUSIONS: Peer simulation was perceived by students as valuable in
preparing them for clinical placement, despite a perceived lack of realism. These
findings support the use of peer simulation as an alternative to the use of more
formalized standardized patients in an undergraduate physiotherapy program.
Further investigation is required to establish a detailed cost analysis of the
program and to determine the amount of realism required to optimize the benefits
of this promising educational strategy.
PMID- 29346227
TI - Refractory Pain Management in Amyloid-Associated Peripheral Neuropathy.
AB - OBJECTIVE: Systemic amyloidosis is a disease that often involves multiple organ
systems, including the peripheral nervous system. Patients may present with
severe, refractory neuropathic pain; however, the optimal treatment approach for
pain for these patients remains unclear. CASE REPORT: A man with severe,
refractory neuropathic pain in his bilateral upper and lower extremities and the
trunk secondary to amyloid neuropathy is presented. Multiple medication trials,
including neuropathic and opioid agents, produced considerable adverse effects
and minimal relief. Scrambler therapy, a novel electrical stimulation modality,
was used and was associated with substantial short-term but nonsustained benefit.
Spinal cord stimulation was considered, but given his diffuse symptoms, it was
deemed a less-than-optimal approach. Ultimately, an intrathecal drug delivery
system was placed with infusion of hydromorphone, resulting in substantial pain
reduction in all involved areas and with an improved adverse effect profile. This
intervention resulted in immense improvement in the patient's quality of life,
despite progression of his systemic amyloidosis. CONCLUSIONS: Severe pain in the
setting of amyloid neuropathy is often difficult to treat. To our knowledge, this
represents the first report of Scrambler therapy or an implanted intrathecal drug
delivery system used for a patient with refractory amyloidosis-related
neuropathic pain, resulting in substantial analgesic benefit and improved quality
of life.
PMID- 29346228
TI - Analgesia of Combined Femoral Triangle and Obturator Nerve Blockade Is Superior
to Local Infiltration Analgesia After Total Knee Arthroplasty With High-Dose
Intravenous Dexamethasone.
AB - BACKGROUND AND OBJECTIVES: High-dose intravenous dexamethasone reduces the
postoperative opioid requirement and is often included in the multimodal
analgesia strategy after total knee arthroplasty (TKA). Combined obturator nerve
and femoral triangle blockade (OFB) reduces the opioid consumption and pain after
TKA better than local infiltration analgesia (LIA). The question is whether
preoperative high-dose intravenous dexamethasone would cancel out the superior
analgesic effect of OFB compared with LIA. The aim was to evaluate the analgesic
effect of OFB versus LIA after TKA when all patients received high-dose
intravenous dexamethasone. METHODS: Eighty-two patients were randomly assigned
either to OFB or LIA after primary unilateral TKA. All patients received 16 mg
dexamethasone. Primary outcome was morphine consumption via patient-controlled
analgesia during the first 20 postoperative hours. Secondary outcomes were pain,
nausea, dizziness, and length of hospital stay. RESULTS: Seventy-four patients
were included in the analysis. Median total intravenous morphine consumption
during the first 20 postoperative hours was 6 mg (interquartile range [IQR], 2-18
mg) in the OFB group and 20 mg (IQR, 12-28 mg) in the LIA group. The 14-mg
difference (95% confidence interval, 6.4-18.0 mg) was significant (P < 0.001).
There was no difference in pain score at rest at 20 hours postoperatively: 2
(IQR, 1-4) in the OFB group and 3 (IQR, 2-5) in the LIA group. CONCLUSIONS:
Combined OFB reduces morphine consumption better than LIA after TKA even when all
patients received high-dose intravenous dexamethasone. CLINICAL TRIAL
REGISTRATION: This study was registered at ClinicalTrials.gov, identifier
NCT02374008.
PMID- 29346229
TI - Anatomical Variations of the Vertebral Artery in the Upper Cervical Spine:
Clinical Relevance for Procedures Targeting the C1/C2 and C2/C3 Joints.
AB - BACKGROUND AND OBJECTIVES: Accidental breach of the vertebral artery (VA) during
the performance of cervical pain blocks can result in significant morbidity.
Whereas anatomical variations have been described for the foraminal (V2) segment
of the VA, those involving its V3 portion (between the C2 transverse process and
dura) have not been investigated and may be of importance for procedures
targeting the third occipital nerve or the lateral atlantoaxial joint. METHODS:
Five hundred computed tomography angiograms of the neck performed in patients
older than 50 years for the management of cerebrovascular accident or cervical
trauma (between January 2010 and May 2016) were retrospectively and independently
reviewed by 2 neuroradiologists. Courses of the VA in relation to the lateral
aspect of the C2/C3 joint and the posterior surface of the C1/C2 joint were
examined. For the latter, any medial encroachment of the VA (or one of its
branches) was noted. The presence of a VA loop between C1 and C2 and its distance
from the upper border of the superior articular process (SAP) of C3 were also
recorded. If the VA loop coursed posteriorly, its position in relation to 6
fields found on the lateral aspects of the articular pillars of C2 and C3 was
tabulated. RESULTS: At the C1/C2 level, the VA coursed medially over the lateral
quarter of the dorsal joint surface in 1% of subjects (0.6% and 0.4% on the left
and right sides, respectively; P = 0.998). A VA loop originating between C1 and
C2 was found to travel posteroinferiorly over the anterolateral aspect of the
inferior articular pillar of C2 in 55.5% of patients on the left and 41.9% on the
right side (P < 0.001), as well as over the SAP of C3 in 0.4% of subjects. When
present in the quadrant immediately cephalad to the C3 SAP, VA loops coursed
within 2.0 +/- 1.5 and 3.3 +/- 2.5 mm on the left and right sides, respectively,
of its superior aspect (P < 0.001). CONCLUSIONS: The VA commonly travels adjacent
to areas targeted by third occipital nerve procedures and more rarely over the
access point for lateral atlantoaxial joint injections. Modifications to existing
techniques may reduce the risk of accidental VA breach.
PMID- 29346230
TI - Chronic Hematoma of the Neck.
AB - Chronic hematomas are defined as hematomas with slow, progressive growth over
many weeks. They are an extremely rare cause of acute neck swelling in the
pediatric population. They consist of an organized central mass of blood with
granulation tissue and fibrotic changes peripherally. The presence of a capsule
prevents resorption but allows for intracapsular bleeding with subsequent
expansion. We describe a case of a 6-year-old girl who presented to the emergency
department with a spontaneously occurring left neck mass in the supraclavicular
region. A possible neoplasm was suggested on imaging. The patient was referred to
a head and neck surgeon, she underwent a thorough workup, and the mass was
ultimately surgically excised. Histologically, the mass was confirmed to be a
chronic hematoma. The patient recovered uneventfully, and there has been no
recurrence.
PMID- 29346231
TI - The Complex Association of Race/Ethnicity With Pain Treatment Quality in an Urban
Medical Center With 2 Pediatric Emergency Departments.
AB - OBJECTIVE: This study aimed to explore racial differences in analgesia quality.
METHODS: A retrospective cross-sectional study of 24,733 visits by individuals 21
years or younger with pain scores of 4 to 10 was performed using electronic
medical records. We compared 2 process metrics, treatment with any analgesics
within 60 minutes and treatment with opioids within 60 minutes, and one outcome
metric, a reduction in pain score by 2 or more points within 90 minutes.
Multivariable logistic regression adjusted for the effects of patient
characteristics and health status. We also determined variations in analgesia
quality among those with severe pain. RESULTS: When compared with white children,
black children were more likely to receive any analgesia (adjusted odds ratio
[aOR], 1.94; 95% confidence interval, 1.71-2.21), but both blacks (aOR, 0.66;
0.51-0.85) and Hispanics (aOR, 0.56; 0.39-0.80) were less likely to receive
opioids. Blacks were more likely to reduce their pain score (aOR, 1.50; 1.28
1.76).Among children with severe pain, both blacks and Hispanics were more likely
to receive any analgesia (black: aOR, 2.05 [1.71-2.46]; Hispanic: aOR, 1.29 [1.05
1.59]), and Hispanic children were less likely to receive opioids (aOR, 0.58;
0.37-0.91). Again, black children were more likely to reduce their pain score
(aOR, 1.42; 1.13-1.79). CONCLUSIONS: The relationship between race/ethnicity and
analgesia is complex. Although minority children were less likely to receive
opioids, black children had better treatment outcomes. Future studies should
explore clinical response to analgesia in addition to process measures to better
understand if differential treatment may be justified to achieve equitable care
outcomes.
PMID- 29346232
TI - Use of Point-of-Care Ultrasound to Guide Pediatric Gastrostomy Tube Replacement
in the Emergency Department.
AB - The presentation of a pediatric patient to the emergency department for a
malfunctioning or dislodged gastrostomy tube (G-tube) is not uncommon. As such,
these tubes are often replaced at the bedside. Improper placement can result in a
number of complications, including perforation, fistula tract formation,
peritonitis, and sepsis. The current criterion standard method to confirm proper
G-tube placement is contrast-enhanced radiography. However, point-of-care
ultrasound may be an alternative method to guide and confirm pediatric G-tube
replacement in the emergency department. We report a series of cases on this
novel point-of-care ultrasound application.
PMID- 29346233
TI - Video Recordings to Analyze Preventable Management Errors in Pediatric
Resuscitation Bay.
AB - OBJECTIVE: In treating patients of different ages and diseases in the pediatric
resuscitation bay, management errors are common. This study aimed to analyze the
adherence to advanced trauma life support and pediatric advanced life support
guidelines and identify management errors in the pediatric resuscitation bay by
using video recordings. METHODS: Video recording of all patients admitted to the
pediatric resuscitation bay at University Children's Hospital Zurich during a 13
month period was performed. Treatment adherence to advanced trauma life support
guidelines and pediatric advanced life support guidelines and errors per patient
were identified. RESULTS: During the study period, 128 patients were recorded
(65.6% with surgical, 34.4% with medical diseases). The most common causes for
admission were traumatic brain injury (21.1%), multiple trauma (20.3%), and
seizures (14.8%). There was a statistically significant correlation between
accurate handover from emergency medical service to hospital physicians and
adherence to airway, breathing, circulation, and disability sequence (correlation
coefficient [CC], 0.205; P = 0.021), existence of a defined team leader and
adherence to airway, breathing, circulation, and disability sequence (CC, 0.856;
P < 0.001), and accurate hand over and existence of a defined team leader (CC,
0.186; P = 0.037). Unexpected errors were revealed. Cervical spine
examination/stabilization was omitted in 40% of admitted surgical patients, even
in 20% of patients with an injury of spine/limbs. CONCLUSIONS: Video recording is
a useful tool to evaluate patient management in the pediatric resuscitation bay.
Analyzing errors of missing the adherence to the guidelines helps to pay
attention and focus on specific items to improve patient care.
PMID- 29346234
TI - A Qualitative Study of Multidisciplinary Providers' Experiences With the Transfer
Process for Injured Children and Ideas for Improvement.
AB - OBJECTIVE: Most injured children initially present to a community hospital, and
many will require transfer to a regional pediatric trauma center. The purpose of
this study was 1) to explore multidisciplinary providers' experiences with the
process of transferring injured children and 2) to describe proposed ideas for
process improvement. METHODS: This qualitative study involved 26 semistructured
interviews. Subjects were recruited from 6 community hospital emergency
departments and the trauma and transport teams of a level I pediatric trauma
center in New Haven, Conn. Participants (n = 34) included interprofessional
providers from sending facilities, transport teams, and receiving facilities.
Using the constant comparative method, a multidisciplinary team coded transcripts
and collectively refined codes to generate recurrent themes across interviews
until theoretical saturation was achieved. RESULTS: Participants reported that
the transfer process for injured children is complex, stressful, and necessitates
collaboration. The transfer process was perceived to involve numerous
interrelated components, including professions, disciplines, and institutions.
The 5 themes identified as areas to improve this transfer process included 1)
Creation of a unified standard operating procedure that crosses
institutions/teams, 2) Enhancing 'shared sense making' of all providers, 3)
Improving provider confidence, expertise, and skills in caring for pediatric
trauma transfer cases, 4) Addressing organization and environmental factors that
may impede/delay transfer, and 5) Fostering institutional and personal
relationships. CONCLUSIONS: Efforts to improve the transfer process for injured
children should be guided by the experiences of and input from multidisciplinary
frontline emergency providers.
PMID- 29346236
TI - A Teenager With Acute Anterograde Amnesia.
AB - Isolated amnesia is an uncommon presenting complaint in the pediatric age group.
We report the case of an 18-year-old woman who presented with the acute onset of
memory difficulty and an otherwise normal neurologic examination. Brain magnetic
resonance imaging demonstrated inflammation in the bilateral temporal lobes.
Serum and cerebrospinal fluid testing ultimately revealed a diagnosis of
autoimmune encephalitis. Although rare, the acute onset of isolated amnesia
deserves a prompt, comprehensive evaluation.
PMID- 29346235
TI - Posttraumatic Stress in Children After Injury: The Role of Acute Pain and Opioid
Medication Use.
AB - OBJECTIVES: After injury, many children experience posttraumatic stress symptoms
(PTSS) that negatively impact recovery. Acute pain and PTSS share neurobiological
pathways, and acute dosage of morphine has been linked to reduced PTSS in
naturalistic studies. However, the complex interactions between pain, morphine
and other opioid use, and PTSS have yet to be investigated in robust pediatric
samples.This prospective, longitudinal study examined relationships between acute
pain, opioid medications, and PTSS after pediatric injury. METHODS: Ninety-six
children aged 8 to 13 years (mean = 10.60, SD = 1.71), hospitalized for
unintentional injury, completed assessments at baseline (T1) and 12 weeks (T2)
later. Pain ratings and opioid administration data were obtained via chart
review. RESULTS: Structural equation modeling revealed that worst pain endorsed
during hospitalization was positively associated with concurrent and later PTSS
when controlling for evidence-based risk factors (ie, age, sex, prior trauma
history, traumatic appraisals of injury event, heart rate). Neither opioid
medications overall nor morphine specifically (milligram/kilogram/day)
administered during hospitalization mediated the relationship between pain and T2
PTSS. CONCLUSIONS: Pain during hospitalization may increase susceptibility for
persistent PTSS above and beyond the influence of other empirical risk factors.
Findings suggest that pain assessment may be a useful addition to pediatric PTSS
screening tools and highlight the need for additional research on pharmacological
secondary prevention approaches. Given that inadequate pain control and
persistent PTSS each hinder recovery and long-term functioning, better
understanding of interactions between acute pain and PTSS after injury is
essential for improving screening, prevention, and early intervention efforts.
PMID- 29346237
TI - Pediatric Pelvic Fractures and Differences Compared With the Adult Population.
AB - INTRODUCTION: Although pelvic fractures in children are rare, because of
anatomical differences between an adult's skeleton and a child's skeleton, these
lesions in the pediatric population have specific characteristics that need to be
borne in mind when dealing with them. MATERIALS AND METHODS: A retrospective
chart review was performed on the pelvic fractures in skeletally immature
patients treated in our hospital in the last 20 years. RESULTS: Eighty-one pelvic
fractures in children were treated between 1993 and 2013. The mean age was 9.98
years, with 61.7%(50/81) boys and 38.2% (31/81) girls. A traffic accident was the
main injury mechanism (74%, 60/81), and height fall was in second place (16%,
13/81). Following Tile pelvic fracture classification, type A2 was the most
frequent (58.04%, 47/81); and following Torode and Zieg classification, type IIIA
(45.68%, 37/81).Associated injuries were present in 77.8% (63/81) of the
patients; fractures of other bones and head trauma were the most frequent. An
acetabular fracture was present in 13.5% (11/81) of the patients.Nonsurgical
treatment was chosen for all the pelvic fractures except in 4 patients, which
required surgical management for their pelvic injuries. Blood transfusion was
required in 32% (26/81) of the patients, and arterial embolization was not needed
in any case. Furthermore, 11.1% (9/81) required a stay in the pediatric care
unit, and the death rate was 8.64% (7/81).The mean length of hospital stay was
12.4 days. CONCLUSIONS: Because of the specific characteristics of pelvic
fractures in children, fracture patterns are less severe than those of adults,
but the injury mechanisms are high-energy traumas. The rate of associated
injuries is very high, and a multidisciplinary management in pediatric trauma
centers is needed to treat these patients.
PMID- 29346238
TI - Trends in Severe Pediatric Emergency Conditions in a National Cohort, 2008 to
2014.
AB - OBJECTIVE: The objective of this study was to determine the incidence and recent
trends in serious pediatric emergency conditions. METHODS: We conducted a cross
sectional study of the Nationwide Emergency Department Sample from 2008 through
2014, and included patients with age below 18 years with a serious condition,
defined as each diagnosis group in the diagnosis grouping system with a severity
classification system score of 5. We calculated national incidences for each
serious condition using annualized weighted condition counts divided by annual
United States census child population counts. We determined the highest-incidence
serious conditions over the study period and calculated percentage changes
between 2008 and 2014 for each serious condition using a Poisson model. RESULTS:
The 2008 incidence of serious conditions across the national child population was
1721 visits per million person-years (95% confidence interval, 1485-1957). This
incidence increased to 2020 visits per million person-years (95% confidence
interval, 1661-2379) in 2014. The most common serious conditions were serious
respiratory diseases, septicemia, and serious neurologic diseases. Anaphylaxis
was the condition with the largest change, increasing by 147%, from 101 to 249
visits per million person-years. CONCLUSIONS: The most common serious condition
in children presenting to United States emergency departments is serious
respiratory disease. Anaphylaxis is the fastest increasing serious condition.
Additional research attention to these diagnoses is warranted.
PMID- 29346239
TI - FACTORS ASSOCIATED WITH DEVELOPMENT OF DISSOCIATED OPTIC NERVE FIBER LAYER
APPEARANCE IN THE PIONEER INTRAOPERATIVE OPTICAL COHERENCE TOMOGRAPHY STUDY.
AB - PURPOSE: To assess the relationship of dissociated optic nerve fiber layer
(DONFL) and intraoperative membrane-peeling dynamics as visualized using
intraoperative optical coherence tomography (OCT), and to evaluate the functional
implications of DONFL. METHODS: This was a post hoc analysis of eyes undergoing
membrane peeling for vitreomacular interface disorders in the prospective PIONEER
intraoperative OCT study. Retinal layer measurements in preincision and postpeel
intraoperative OCT images were obtained. The primary outcome was development of
DONFL appearance on spectral domain OCT at 6-month follow-up. Secondary outcomes
included correlation of DONFL with surgical technique, surgical indication,
intraoperative OCT findings, and retinal sensitivity. RESULTS: Ninety-five eyes
were included. The prevalence of DONFL at 6 months was 36%. Increased inner
retinal layer thickness on intraoperative OCT immediately after membrane peeling
was associated with development of DONFL (P < 0.01). Macular hole repair was
significantly associated with DONFL appearance. Peel technique (forceps vs.
diamond-dusted membrane scraper) was not associated with DONFL. There was no
difference in retinal sensitivity or visual acuity between eyes with or without
DONFL. CONCLUSION: Acute postpeel increase in inner retinal thickness and macular
hole repair were associated with development of DONFL appearance. However, it is
unclear whether the surgical indication (e.g., macular hole) or the surgical
manipulations performed (e.g., internal limiting membrane peeling) is the major
factor that has an impact on DONFL appearance. Overall, these findings suggest
that one mechanism in the development of DONFL appearance may be intraoperative
trauma to the inner retina, potentially during internal limiting membrane peeling
(e.g., macular hole repair).
PMID- 29346240
TI - RESPONSE OF INFLAMMATORY CYSTOID MACULAR EDEMA TO TREATMENT USING ORAL
ACETAZOLAMIDE.
AB - PURPOSE: To determine the treatment effect of oral acetazolamide on refractory
inflammatory macular edema. METHODS: A retrospective review of identified
patients with uveitic or pseudophakic macular edema treated using acetazolamide
between 2007 and 2014. Visual acuity and central macular subfield thickness was
determined at baseline and at first follow-up. Baseline optical coherence
tomography features were analyzed as predictors of acetazolamide response.
RESULTS: Sixteen patients (19 eyes) of 61 screened met all criteria. Mean age was
57.9 years (19.7-81.1). The most common diagnosis was idiopathic uveitis (n = 6,
31.6%). Mean uveitis duration was 4.4 years (0.2-27.5). Average central macular
subfield thickness decreased significantly (from 471.8 +/- 110.6 MUm to 358.3 +/-
50.4 MUm) (P < 0.0001). Average visual acuity (logarithm of the minimum angle of
resolution) improved significantly from 20/54 (0.43 +/- 0.25) to 20/37 (0.27 +/-
0.16) (P = 0.003). Pretreatment optical coherence tomographies demonstrated
intraretinal fluid (n = 19, 100%), subretinal fluid (n = 8, 42.1%), epiretinal
membrane (n = 13, 68.3%), and vitreomacular traction (n = 1, 5.2%). No optical
coherence tomography characteristic was predictive of a response to therapy.
CONCLUSION: There is a significant benefit to vision and central macular subfield
thickness after acetazolamide treatment in patients with inflammatory macular
edema. In patients with refractory inflammatory macular edema, treatment using
acetazolamide can provide anatomical and visual benefit without corticosteroid
related adverse effects.
PMID- 29346241
TI - CHRONIC CENTRAL SEROUS CHORIORETINOPATHY: Early and Late Morphological and
Functional Changes After Verteporfin Photodynamic Therapy.
AB - PURPOSE: To describe early and late morphological and functional changes in
subjects receiving photodynamic therapy (PDT) for chronic central serous
chorioretinopathy. METHODS: Patients with chronic central serous
chorioretinopathy were prospectively enrolled and received standard PDT. At the
baseline examination, each subject underwent complete ophthalmological
examination, including best-corrected visual acuity (BCVA) assessment,
fluorescein angiography and indocyanine green angiography, spectral domain
optical coherence tomography, and microperimetry. Spectral domain optical
coherence tomography, microperimetry, and BCVA assessment were repeated in
multiple sections over 7 days after PDT and at 1-, 3-, and 12-month intervals.
Main outcome measures were: identification of early changes (1-week examination)
in BCVA, retinal sensitivity, and spectral domain optical coherence tomography
parameters and their influence on outcomes at the 1-year follow-up. RESULTS:
Three main patterns of early response to PDT were identified during the 1-week
examination. The neurosensory retinal detachment most frequently decreased
rapidly (12/19 pts), with complete resolution in 50% of cases. An increase in
neurosensory retinal detachment height was registered in 16% (3/19) of cases,
whereas in 21% (4/19), a large fluctuation in neurosensory retinal detachment was
encountered. Best-corrected visual acuity declined significantly in 5/12 patients
in the first group and was stable or improved in the remaining cases. Overall,
retinal sensitivity diminished in 16/19 subjects, with a mean worsening of 2.56
dB (P = 0.0002). At the 12-month examination, final mean BCVA improved by 14.4
letters (P = 0.001) and a similar progressive recovery in the retinal sensitivity
was observed (+2.69 dB, P = 0.0039). The neurosensory retinal detachment
completely resolved in 18/19 (95%) cases, with a parallel significant reduction
in central foveal choroidal thickness (P < 0.0001). CONCLUSION: Three patterns of
early response to standard PDT can be identified. Although an early and abrupt
reduction in BCVA and retinal sensitivity after treatment is possible, this does
not compromise a final improvement in visual functions.
PMID- 29346242
TI - PREVALENCE AND CLINICAL CHARACTERISTICS OF PACHYDRUSEN IN POLYPOIDAL CHOROIDAL
VASCULOPATHY: Multimodal Image Study.
AB - PURPOSE: To investigate the prevalence of a newly defined drusen type,
pachydrusen, soft drusen, and subretinal drusenoid deposits in eyes with
polypoidal choroidal vasculopathy and fellow eyes and the relationship between
each drusen type and the choroidal thickness, vascular morphology, and
hyperpermeability. METHODS: The 169 eyes of 90 patients with polypoidal choroidal
vasculopathy were retrospectively reviewed. The prevalence of each drusen type
was evaluated using color fundus photography and optical coherence tomography.
The choroidal thickness and presence of pachyvessels on optical coherence
tomography and choroidal vascular hyperpermeability on indocyanine green
angiography were compared among the drusen groups. RESULTS: Pachydrusen, soft
drusen, and subretinal drusenoid deposits were found in 49.3%, 12.3%, and 6.9% in
polypoidal choroidal vasculopathy eyes. The mean subfoveal choroidal thickness of
the pachydrusen, soft drusen, and subretinal drusenoid deposit groups was 403.1,
184.4, and 176.4 um. The pachydrusen group showed significantly thicker choroid
than the others. The choroidal hyperpermeability was noticed at 41.7%, 0%, and 0%
and the pachyvessel was observed at 80.6%, 44.4%, and 40% in pachydrusen, soft
drusen, and subretinal drusenoid deposit groups, respectively. CONCLUSION: In
patients with polypoidal choroidal vasculopathy, pachydrusen was prevalent and
associated with thicker choroid. Polypoidal choroidal vasculopathy with
pachydrusen was highly associated with choroidal vascular hyperpremeability and
pachyvessel morphology than other types of drusen.
PMID- 29346243
TI - PARS PLANA VITRECTOMY WITH ANTERIOR CHAMBER VERSUS GORE-TEX SUTURED POSTERIOR
CHAMBER INTRAOCULAR LENS PLACEMENT: LONG-TERM OUTCOMES.
AB - PURPOSE: To compare clinical outcomes of combined pars plana vitrectomy (PPV)
with anterior chamber intraocular lens (ACIOL) placement versus scleral fixation
of a posterior chamber intraocular lens (PCIOL) using Gore-Tex suture. METHODS:
Retrospective, interventional case series of eyes undergoing combined PPV and IOL
placement for retained lens material, aphakia, or dislocated IOL. Eyes with
history of amblyopia, corneal opacity, retinal, or optic nerve disease were
excluded. Outcome measures were change in visual acuity and occurrence of
postoperative complications with minimum follow-up of 1 year. RESULTS: Sixty
three eyes of 60 patients were identified. Thirty-three eyes underwent combined
PPV and ACIOL placement and 30 eyes underwent combined PPV and scleral fixation
of a PCIOL using Gore-Tex suture. Mean follow-up was 502 +/- 165 days (median
450, range 365-1,095 days). In the ACIOL group, mean visual acuity improved from
20/914 preoperatively to 20/50 postoperatively (P < 0.001). In the scleral
fixated PCIOL group, mean visual acuity improved from 20/677 preoperatively to
20/46 postoperatively (P < 0.001). No difference in visual acuity was noted
between groups at 1-year (P = 0.91) or final follow-up (P = 0.62). Regarding
postoperative complications, eyes undergoing ACIOL placement had a significantly
higher rate of transient corneal edema (30.3 vs. 6.7%, P = 0.02) compared with
eyes undergoing scleral fixation of a PCIOL. CONCLUSION: Combined PPV with ACIOL
placement or scleral fixation of a PCIOL with Gore-Tex suture were well
tolerated. The techniques resulted in similar visual outcomes at minimum follow
up of 1 year.
PMID- 29346244
TI - COMPARING FUNDUS FLUORESCEIN ANGIOGRAPHY AND SWEPT-SOURCE OPTICAL COHERENCE
TOMOGRAPHY ANGIOGRAPHY IN THE EVALUATION OF DIABETIC MACULAR PERFUSION.
AB - PURPOSE: To compare fundus fluorescein angiography (FFA) and swept-source optical
coherence tomography angiography (SS-OCTA) in the evaluation of macular perfusion
in diabetic patients. METHODS: Forty-one eyes (21 diabetic patients) seen at
Moorfields Eye Hospital (London) over a 1-month interval underwent color fundus
photography, FFA, and SS-OCTA imaging of the capillary superficial plexus using 2
different protocols: 3 * 3 mm and 4.5 * 4.5 mm. Quantitative assessment (foveal
avascular zone diameters and area), qualitative analysis (macroscopic and
microscopic levels) and Early Treatment Diabetic Retinopathy Study diabetic
macular ischemia grading were performed. Artifacts were recorded. Intraclass
correlation coefficients and weighted kappa values were calculated. RESULTS: Mean
(SD) foveal avascular zone area was 0.695 (0.52) mm on FFA, 0.627 (0.54) mm on SS
OCTA 3 * 3 and 0.701 (0.54) mm on SS-OCTA 4.5 * 4.5 protocol. Intraclass
correlation coefficients showed good agreement between FFA and SS-OCTA for both
vertical diameter and foveal avascular zone area measurements. The agreement
between SS-OCTA 3 * 3 and 4.5 * 4.5 was good for all quantitative measurements.
Weighted kappa for diabetic macular ischemia grading showed low to fair agreement
between FFA and SS-OCTA, whereas the agreement was good between two different SS
OCTA protocols. CONCLUSION: Swept-source OCTA is a reproducible technique in the
assessment of macular perfusion in diabetic patients with special regards to
foveal avascular zone analysis. The agreement with FFA is limited especially for
diabetic macular ischemia grading. Fundus fluorescein angiography is more
sensitive in identifying microaneurysms.
PMID- 29346245
TI - Diagnostic Yield and Safety of Bronchoscopist-directed Moderate Sedation With a
Bolus Dose Administration of Propofol During Endobronchial Ultrasound
Bronchoscopy.
AB - BACKGROUND: The propofol use for moderate sedation (MS) during endobronchial
ultrasound (EBUS) bronchoscopy is primarily restricted for use by an
anesthesiologist because of safety concerns. The goals of this study were to
demonstrate the safety and the diagnostic yield of the use of propofol by
bronchoscopists and trained endoscopy nurses during EBUS bronchoscopy without
intubation. METHODS: We tested a bolus propofol administration protocol targeting
MS for EBUS bronchoscopy. A fixed initial dose of 40 mg of propofol along with a
fixed 50 mcg fentanyl dose were administered. Sedation assessment was performed
every 2 minutes, and repeated bolus doses of propofol were given to maintain MS
under the direction of the bronchoscopist. RESULTS: A total of 122 subjects
underwent EBUS bronchoscopy with a goal of MS from August 2015 to April 2017. In
total, 110 subjects who underwent convex EBUS bronchoscopy under MS with propofol
were included in the analysis. Median procedure duration was 57 minutes (range,
15 to 97 min). Deep sedation and agitation-related delay were occurred in 14 and
21 subjects, respectively. Hemodynamic instability and hypoxemia occurred in 23
subjects. However, there was no need for vasopressors or artificial airway
placement. Median of total propofol dose per case was 560 mg. Diagnostic yield
for malignancy and granuloma was 68%, and a median of 4 lymph node stations were
sampled per subject. All specimens with adenocarcinoma were sufficient for
genetic marker analysis. There were no major sedation-related complications.
CONCLUSION: A bolus administration of propofol during EBUS bronchoscopy provided
excellent adequacy of sedation and well tolerance safety profile.
PMID- 29346246
TI - Comparison of Diagnostic Potential of Narrow Band Imaging Bronchoscopy Over White
Light Bronchoscopy in Lung Cancer.
AB - BACKGROUND: Worldwide, lung cancer is the largest contributor to new cancer
diagnoses and to death from cancer. Narrow band imaging (NBI) is a novel
bronchoscopic technique which enables detailed examination of submucosal
microcapillary grid and showed great potential in early detection of malignant
lesions of the bronchial mucosa. The aim of this study was to compare diagnostic
potential of NBI bronchoscopy over white light (WL) bronchoscopy in lung cancer.
METHODS: We enrolled 187 patients having clinical and radiologic findings highly
suspicious of lung cancer. Patients were further divided into 2 groups: NBI group
(n=102), and control WL group (n=85). Bronchoscopy examination was performed with
respective visualization modes and all pathologic lesions were biopsied and
histologically confirmed. RESULTS: On NBI bronchoscopy, malignancy was suspected
in 69 patients, of whom 62 had malignancy, and 33 patients were suspected of
inflammation, of whom 32 had inflammation and only 1 patient had malignancy.
Under WL bronchoscopy, 54 patients were suspected of malignancy, of whom 36 had
malignancy, and 31 patients were suspected of inflammation, of whom 23 had
inflammatory disease and 8 had malignancy. NBI bronchoscopy had sensitivity
98.1%, specificity 82.05%, positive predictive value 89.86% and negative
predictive value 96.97% in comparison to standard WL bronchoscopy which had
sensitivity 81.82%, specificity 56.10%, positive predictive value 66.67% and
negative predictive value 74.19%. CONCLUSION: NBI bronchoscopy demonstrated
better results in comparison to WL bronchoscopy. The presence of pathologic
vascularization of the tumor helps to better identify the malignant process.
Inflammatory changes in the mucosa can be easily differentiated from malignant
changes by the appearance of vessels.
PMID- 29346247
TI - Concurrent Versus Sequential Intrapleural Instillation of Tissue Plasminogen
Activator and Deoxyribonuclease for Pleural Infection.
AB - BACKGROUND: Treatment of pleural infection with instillation of sequential
intrapleural tissue plasminogen activator (tPA) and human recombinant
deoxyribonuclease (DNase) twice daily for a total of 6 doses has been shown to
decrease surgical referral and improve radiographic imaging. This labor-intensive
regimen was empirically chosen. Thus, it remains unclear whether the 2 drugs can
be administered immediately one after the other (concurrent administration)
instead of instilling them separately with a 1-hour to 2-hour interval in between
(sequential administration). The aim of this study was to compare the efficacy
and safety of sequential versus concurrent tPA/DNase therapy in patients with
pleural infection. METHODS: This was a prospective observational study.
Consecutive patients with pleural infection who received concurrent and
sequential tPA/DNase were included. The initiation and number of doses of
tPA/DNase therapy were based on the amount of pleural fluid drainage, clinical
response and radiographic findings. RESULTS: A total of 38 patients with pleural
infection received tPA/DNase treatment: 18 in the sequential group and 20 in the
concurrent group. Treatment was successful in 77.7% in the sequential group and
75% in concurrent group (P=0.57). There was no statistically significant
difference between the 2 treatment groups (sequential and concurrent) in median
pleural fluid drainage (P=0.45), median volume of pleural effusion estimated on
chest computed tomography scan (P=0.4) or median hemithorax occupied by effusion
on chest radiography (P=0.83) following intrapleural therapy. One patient
required a blood transfusion for gradual pleural blood loss in each treatment
group. Pain needing escalation of analgesia affected 3 patients in each arm but
none required cessation of therapy. CONCLUSION: A simpler regimen of concurrent
administration of intrapleural tPA/DNase as compared with sequential intrapleural
therapy is safe, effective, and represents a viable option for the management of
pleural infection.
PMID- 29346248
TI - The Utility of Ultrasound to Diagnose Tunnel-Tract Infection Related to
Indwelling Pleural Catheters.
AB - Indwelling pleural catheter (IPC) infections lead to increased morbidity and
treatment failure in patients with chronic recurrent pleural effusions.
Ultrasonography is a readily available diagnostic tool used by pulmonologists on
a daily basis. Ultrasonography has been used to identify the etiology of
indwelling peritoneal catheter obstruction, including infection of the exit site
and tunnel tract. The use of ultrasonography to identify tunnel-tract infection
involving IPC has not been reported. We describe the ultrasonographic
characteristics of 3 cases of confirmed tunnel-tract infection and compared them
with noninfected chronic IPCs. Ultrasonographic evaluation of the soft tissue
tunnel tract can accurately identify fluid collections around the catheter and
cuff, which is highly suggestive of tunnel-tract infection.
PMID- 29346249
TI - 1% Versus 2% Lignocaine for Airway Anesthesia in Flexible Bronchoscopy Without
Lignocaine Nebulization (LIFE): A Randomized Controlled Trial.
AB - BACKGROUND: The ideal concentration of lignocaine for topical anesthesia in
bronchoscopy remains investigational. In this randomized, double blind study, we
compared 1% versus 2% lignocaine for topical anesthesia. METHODS: Consecutive
patients undergoing bronchoscopy were randomized to receive either 1% or 2%
lignocaine solution by spray-as-you-go technique. All received 10% lignocaine
spray to the oropharynx along with nasal 2% lignocaine gel. Nebulized lignocaine
was not administered. Primary outcomes were operator-rated overall procedural
satisfaction, visual analogue scale (VAS)-rated and operator-rated cough, VAS.
Secondary objectives were total lignocaine dose administered, patient-rated pain
on faces pain scale, cumulative dose of lignocaine and procedural complications.
RESULTS: A total of 500 patients (250 in each group) were randomized. Baseline
characteristics were comparable. Operator-rated overall procedural satisfaction,
VAS (72.05+/-20.16 and 72.20+/-21.96 in 1% and 2% group respectively; P=0.93) and
operator-rated cough, VAS [1% group: 19.1 (12.6-34.6) and 2% group: 20.6 (12.5
36.9); P>0.05] were similar between the 2 groups. Cumulative dose of lignocaine
used in 2% lignocaine group was greater (220.89+/-12.96 mg in 1% and 319.55+/
19.32 mg in 2% group; P<0.001). Patients receiving sedation were comparable
between the 2 groups. (10% in 1% lignocaine group and 6% in 2% lignocaine group;
P=0.13). Minor complications occurred in 2 patients in each group. CONCLUSION:
One percent lignocaine in flexible bronchoscopy is as efficacious as 2%
lignocaine when administered using the spray as you go technique without
concurrent lignocaine nebulization, at a significantly lower total dose of
lignocaine administered.
PMID- 29346250
TI - Incidence, Etiology, and Clinicopathologic Features of Endobronchial Benign
Lesions: A 10-Year Consecutive Retrospective Study.
AB - BACKGROUND: Airways can be affected by non-neoplastic lesions leading to critical
stenosis of the lumen. Incidence, etiology, and clinical significance of
endobronchial benign lesions are not systematically characterized.This study
aimed to assess the epidemiology of nonmalignant processes involving the
bronchial tree on clinical, pathologic, endoscopic, and radiologic grounds.
METHODS: We retrospectively analyzed bronchoscopy procedures over 10 years at the
Bronchoscopy Unit of Modena University Hospital. All the endoscopically growing
benign lesions with histologic confirmation were considered. For each lesion, we
evaluated demographics, clinical features and outcome, the endoscopic aspect and
radiologic characteristics by means of computed tomography as assessed by 2
experienced radiologists blinded with regard to the diagnosis. RESULTS: Over the
study period, we analyzed 10,431 bronchoscopies and identified 2075 cases of
tracheobronchial alterations. Among these, 11.2% had a benign etiology with an
average annual incidence of 23 new cases/year and a general incidence of 2.2%.
Anthrachosis was the most prevalent bronchial lesion. In total, 22% of benign
lesions presented airway stenosis >50% and required bronchoscopic treatment.
Bronchial stenosis was most frequently observed in tuberculosis (P=0.031) and
aspergillosis (P=0.020) when compared with sarcoidosis. Immunosuppressive status
was significantly associated with endobronchial aspergillosis (P=0.0001) and the
1-year survival from diagnosis resulted significantly lower irrespectively to the
immune system condition. CONCLUSIONS: A consistent proportion of endobronchial
benign lesions are reported. One fifth of these are associated with critical
stenosis of the airway lumen, requiring rigid bronchoscopy. Among these,
aspergillosis is characterized by the poorest prognosis, regardless of host
immunity status.
PMID- 29346251
TI - Combined Endosonography Reduces Time to Diagnose Pulmonary Coccidioidomycosis.
AB - Coccidioidomycosis causes significant morbidity in endemic areas. In the absence
of sensitive diagnostic serologic testing, clinicians have increasingly relied on
lung and lymph node biopsies for diagnosis. Recently, endobronchial ultrasound
guided transbronchial needle aspiration (EBUS-TBNA) has been shown to be an
excellent sampling method for the diagnosis and staging of lung cancers,
especially when combined with endoscopic ultrasound guided fine needle aspiration
(EUS-FNA). We present 13 consecutive cases where EBUS-TBNA and/or EUS-FNA of
pulmonary lymph nodes were performed as part of the workup for pulmonary
coccidioidomycosis. EBUS-TBNA+EUS-FNA led to diagnosis in all nine cases in which
they were performed concurrently, and in the remaining 4 in which either was
performed individually. BAL was performed in all cases with positive results in 5
(38%). The mean time to diagnose by EBUS/EUS (1.6 d) was significantly shorter
than by bronchoalveolar lavage (6.3 d) (P=0.003). The findings indicate that
combined EBUS-TBNA+EUS-FNA for lymph node biopsy facilitates early and accurate
diagnosis of pulmonary coccidioidomycosis.
PMID- 29346252
TI - Sarcoidosis With Pleural Effusion as the Presenting Symptom.
AB - A 65-year-old woman, never smoker, with medical history of hypertension,
nonischemic cardiomyopathy, and moderate pulmonary hypertension presented with
symptomatic bilateral pleural effusions. Thoracentesis revealed a lymphocyte
predominant transudate and was negative for malignancy, microbiologic cultures
were negative for an infectious cause. Chest tomography showed mediastinal and
bilateral hilar lymphadenopathy, lymph node biopsy with endobronchial ultrasound
guided transbronchial needle aspiration showed non-necrotizing granulomas
compatible with sarcoidosis. Echocardiogram showed ejection fraction of 45% and
cardiac workup for sarcoid involvement was negative. Despite overall clinical
management with diuretics, pleural effusion persisted and the patient underwent
medical thoracoscopy with pleural biopsy. Biopsy showed noncaseating granulomas
consistent with sarcoid, with all stains and microbiologic cultures negative for
an infectious etiology. To the best of our knowledge, this is the first described
case of sarcoidosis presenting as large transudative pleural effusion.
PMID- 29346253
TI - An Innovative Solution for Prolonged Air Leaks: The Customized Endobronchial
Silicone Blocker.
AB - BACKGROUND: Prolonged air leak (PAL) is a life-threatening condition that can
present either as bronchopleural fistula, or alveolar-pleural fistula (APF).
Although numerous bronchoscopic treatments are described, they are either
expensive, not widely available in the developing world or have limited success.
We describe our experience with a novel customized endobronchial silicone blocker
(CESB) for PAL treatment. METHODS: This is a retrospective study of PAL patients
who underwent CESB placement. The air leak was localized using a balloon
occlusion test. The CESB was uniquely designed by molding silicone stent pieces
into a conical shape, deployed with rigid bronchoscopy into the appropriate
segment, and reinforced with cyanoacrylate glue to prevent migration. In patients
with APF, pleurodesis was performed after leak resolution to prevent recurrence.
Following this, the CESB was removed after 6 weeks. RESULTS: Forty-nine CESBs
were placed in 31 patients (25 male individuals, 6 female individuals) with mean
age of 49.7+/-19.7 years. The PALs included APF (n=16), bronchopleural fistula
(n=14), and airway-mediastinal fistula (n=1). The average diameter of the CESB
used was 7.9+/-2.9 mm. There was resolution of the PAL in 26 of 31 patients
(84%). The CESB migrated in 5 patients with no adverse events. Pleurodesis was
performed in 13 of 16 patients with APF, to prevent recurrence. No other
significant complications were observed. CONCLUSIONS: CESBs represent a safe,
effective, and innovative approach in the management of PAL. They should be
considered in patients who are not surgical candidates, fail surgery, or those
who have a recurrence following surgery.
PMID- 29346254
TI - Long-term Outcomes of Pediatric En Bloc Compared to Living Donor Kidney
Transplantation: A Single-Center Experience With 25 Years Follow-Up.
AB - BACKGROUND: Pediatric en bloc kidneys are considered marginal for transplantation
into adults. We aimed to compare the long-term outcomes of pediatric en bloc
versus living donor kidney transplantation. METHODS: A retrospective review was
undertaken on pediatric en bloc and living donor kidney transplants performed at
our center between 1990 and 2001. The outcomes compared between the groups
included 25 year graft survival and longitudinal glomerular filtration rate.
RESULTS: There were 72 pediatric en bloc and 75 living donor kidney recipients
included in the analysis. Pediatric donors were 16.9 +/- 11.2 months old and
weighed 10.7 +/- 3.8 kg with terminal serum creatinine of 0.50 +/- 0.45 mg/dL.
Living donors were 40.1 +/- 9.4 years old and serum creatinine was 0.90 +/- 0.16
mg/dL at the time of donation. En bloc kidney recipients had higher dialysis
vintage (23.0 +/- 29.2 months vs 14.3 +/- 14.7 months; P = 0.03), and longer cold
ischemia time (30.5 +/- 9.8 hours vs 2.6 +/- 0.9 hours, P < 0.001). Kaplan-Meier
estimate revealed similar graft survival between the groups up to 27 years of
follow up (log rank P = 0.78). Estimated glomerular filtration rate was
significantly higher in pediatric en bloc kidney recipients from years 5 through
17 posttransplantation. CONCLUSIONS: Pediatric en bloc kidneys conferred long
term graft survival similar to living donor kidneys over a 25-year period after
transplantation along with superior graft function. These findings support
improved utilization of pediatric kidneys for transplantation into adults which
not only helps to alleviate organ shortage but also provide excellent long-term
function.
PMID- 29346255
TI - Safety of BCG Vaccination in Pediatric Liver Transplant Recipients.
PMID- 29346256
TI - Causes, Preventability, and Cost of Unplanned Rehospitalizations Within 30 Days
of Discharge After Lung Transplantation.
AB - BACKGROUND: Unplanned rehospitalizations (UR) within 30 days of discharge are
common after lung transplantation. It is unknown whether UR represents
preventable gaps in care or necessary interventions for complex patients. The
objective of this study was to assess the incidence, causes, risk factors, and
preventability of UR after initial discharge after lung transplantation. METHODS:
This was a single-center prospective cohort study. Subjects completed a modified
short physical performance battery to assess frailty at listing and at initial
hospital discharge after transplantation and the State-Trait Anxiety Inventory at
discharge. For each UR, a study staff member and the patient's admitting or
attending clinician used an ordinal scale (0, not; 1, possibly; 2, definitely
preventable) to rate readmission preventability. A total sum score of 2 or higher
defined a preventable UR. RESULTS: Of the 90 enrolled patients, 30 (33.3%) had an
UR. The single most common reasons were infection (7 [23.3%]) and atrial
tachyarrhythmia (5 [16.7%]). Among the 30 URs, 9 (30.0%) were deemed preventable.
Unplanned rehospitalization that happened before day 30 were more likely to be
considered preventable than those between days 30 and 90 (30.0% versus 6.2%, P =
0.04). Discharge frailty, defined as short physical performance battery less than
6, was the only variable associated with UR on multivariable analysis (odds
ratio, 3.4; 95% confidence interval, 1.1-11.8; P = 0.04). CONCLUSIONS: Although
clinicians do not rate the majority of UR after lung transplant as preventable,
discharge frailty is associated with UR. Further research should identify whether
modification of discharge frailty can reduce UR.
PMID- 29346258
TI - Quantifying Frailty in Post-Lung Transplant Patients-Can We Predict Who Will Need
Readmission?
PMID- 29346257
TI - Association of Cold Ischemia Time With Acute Renal Transplant Rejection.
AB - BACKGROUND: Kidney transplantation holds much promise as a treatment of choice
for patients with end-stage kidney disease. The impact of cold ischemia time
(CIT) on acute renal transplant rejection (ARTR) remains to be fully studied in a
large cohort of renal transplant patients. METHODS: From the Organ Procurement
and Transplantation Network database, we analyzed 63 798 deceased donor renal
transplants performed between 2000 and 2010. We assessed the association between
CIT and ARTR. We also evaluated the association between recipient age and ARTR.
RESULTS: Six thousand eight hundred two (11%) patients were clinically diagnosed
with ARTR. Longer CIT was associated with an increased risk of ARTR. After
multivariable adjustment, compared with recipients with CIT < 12 hours, the
relative risk of ARTR was 1.13 (95% confidence interval, 1.04-1.23) in recipients
with CIT >= 24 hours. The association of CIT and ARTR was more pronounced in
patients undergoing retransplantation: compared with recipients with CIT less
than 12 hours, the relative risk of ARTR was 1.66 (95% confidence interval, 1.01
2.73) in recipients with CIT of 24 hours or longer. Additionally, older age was
associated with a decreased risk of ARTR. Compared with recipients aged 18 to 29
years, the relative risk of ARTR was 0.50 (95% confidence interval, 0.45-0.57) in
recipients 60 years or older. Longer CIT was also associated with increased risk
of death-censored graft loss. Compared with recipients with CIT less than 12
hours, the hazard ratio of death-censored graft loss was 1.22 (95% confidence
interval, 1.14-1.30) in recipients with CIT of 24 hours or longer. CONCLUSIONS:
Prolonged CIT is associated with an increased risk of ARTR and death-censored
graft loss. Older age was associated with a lower risk of ARTR.
PMID- 29346259
TI - Do Patients Supported With Continuous-flow Left Ventricular Assist Device Have a
Sufficient Risk of Death to Justify a Priority Allocation? A Propensity Score
Matched Analysis of Patients Listed in UNOS Status 2.
AB - BACKGROUND: Outcomes of continuous flow left ventricular assist devices (CF
LVADs) as bridge to transplant have significantly improved. The question has
arisen whether patients on CF-LVADs have an increased risk of death on the
waiting list as to justify a priority allocation (status 1). The aim of this
study was to compare the survival after implantation of CF-LVADs with the
survival on the waiting list for patients initially listed in United Network for
Organ Sharing (UNOS) status 2. METHODS: All patients 18 years or older listed for
heart transplantation (HT) in the United States between 2011 and 2013 in UNOS
status 2 with no mechanical circulatory support at time of listing were analyzed.
Patients were divided into 2 groups, depending on whether they received a new CF
LVAD while listed (CF-LVAD group) or not (NO-LVAD) and were further matched on
their propensity score (PS) in a 1:2 ratio. RESULTS: Two hundred eighty-seven CF
LVAD patients were matched to 574 NO-LVAD patients. Survival after CF-LVAD was
significantly lower at 24 months compared with waiting list (75.4 +/- 4.4% vs
91.2 +/- 8.9%, P < 0.0001). Further, survival was not significantly different
between the 2 groups at 24 months after transplantation (81.3 +/- 5.9% vs 86.7 +/
3.3%, P = 0.3). CONCLUSIONS: Survival of patients listed in UNOS status 2 who
receive a CF-LVAD while listed is significantly lower compared to patients who do
not receive mechanical support on the waiting list. The current priority in the
allocation system given to patients on CF-LVAD seems justified. Further
posttransplant survival is not negatively influenced by previous CF-LVAD
implantation.
PMID- 29346260
TI - Race, Risk, and Willingness of End-Stage Renal Disease Patients Without Hepatitis
C Virus to Accept an HCV-Infected Kidney Transplant.
AB - BACKGROUND: Despite effective antiviral treatment, hundreds of kidneys from
deceased donors with hepatitis C virus (HCV) are discarded annually. Little is
known about the determinants of willingness to accept HCV-infected kidneys among
HCV-negative patients. METHODS: At 2 centers, 189 patients undergoing initial or
reevaluation for transplant made 12 hypothetical decisions about accepting HCV
infected kidneys in which we systematically varied expected HCV cure rate,
allograft quality, and wait time for an uninfected kidney. RESULTS: Only 29% of
the participants would accept an HCV-infected kidney under all scenarios, whereas
53% accepted some offers and rejected others, and 18% rejected all HCV-infected
kidneys. Higher cure rate (odds ratio [OR], 3.49; 95% confidence interval [CI],
2.33-5.24 for 95% vs 75% probability of HCV cure), younger donor (OR, 2.34; 95%
CI, 1.91-2.88 for a 20-year-old vs a 60-year-old hypertensive donor), and longer
wait for an uninfected kidney (OR, 1.43; 95% CI, 1.22-1.67 for 5 years vs 2
years) were associated with greater willingness to accept an HCV-infected kidney.
Black race modified the effect of HCV cure rate, such that willingness to accept
a kidney increased less for blacks versus whites as the cure rate improved.
Patients older than 60 years and prior kidney recipients showed greater
willingness to accept an HCV-infected organ. CONCLUSIONS: Most patients will
consider an HCV-infected kidney in some situations. Future trials using HCV
infected kidneys may enhance enrollment by targeting older patients and prior
transplant recipients, but centers should anticipate that black patients'
acceptance of HCV-infected kidneys will be reduced compared with white patients.
PMID- 29346261
TI - The Authors' Reply.
PMID- 29346262
TI - Important Facts About Organ Donation and OPO Performance.
PMID- 29346263
TI - Clinical Application of Real-Time Shear Wave Elastography in Identifying the
Histological Components of Parotid Adenolymphoma.
AB - OBJECTIVE: This study aimed to investigate the relationship between the elastic
modulus and the histological components of parotid adenolymphoma by using real
time shear wave elastography. METHODS: A total of 157 patients, histologically
confirmed as having parotid adenolymphoma, were enrolled in the study. The
maximum and the mean elastic modulus of the parotid mass were measured by using
preoperative shear wave elastography. Parotid adenolymphoma was
histopathologically subdivided into different types based on the relative
proportion of stromal to cellular components. RESULTS: The maximal elasticity of
parotid adenolymphoma ranged from 20.67 to 160.90 kPa, and the mean elasticity
was 83.18 +/- 39.15 kPa. The maximal elasticity of the 3 types of parotid
adenolymphoma was 34.21 to 155.20, 20.67 to 104.20, and 45.89 to 160.90 kPa,
respectively. The mean elasticity of the 3 types of parotid adenolymphoma was
89.16 +/- 40.62, 63.24 +/- 28.07, and 111.10 +/- 37.85 kPa, respectively. The
difference in the maximal elasticity among 3 groups was significant (P < 0.01).
There was no significant difference in maximal elasticity of type II and type III
as compared with type I adenolymphoma (P > 0.05). The maximal elasticity of type
III adenolymphoma was significantly higher than that of type II (P < 0.05, t =
3.12). CONCLUSION: Shear wave elastography depicts parotid adenolymphoma with a
variable appearance because of the relative proportions of stromal to cellular
contents in the mass.
PMID- 29346264
TI - Sonography of the Cecum: Gateway to the Right Lower Quadrant.
AB - Sonography of the cecum has come of age largely as a consequence of the
successful evolution of appendiceal sonography as a useful tool in the evaluation
of patients with right lower-quadrant pain. At some medical centers, graded
compression sonography (GCS) has become the initial imaging study of choice in
the assessment of these individuals. The cecum serves as a helpful anatomic
landmark for localization of the appendix in these examinations-providing a
sonographic starting point in the search for the appendix. During GCS, primary
pathology within the cecum itself can become evident, including a variety of
processes, such as infectious, inflammatory, or neoplastic disorders, whose
presentations commonly mimic that of appendicitis. The accurate diagnosis of
cecal abnormalities and their differentiation from acute appendicitis play
valuable roles in the management of affected patients because the options for
further workup and subsequent treatment vary greatly according to the diagnosis
at hand. Additionally, the compressed cecum often becomes an acoustic window into
the right lower quadrant, revealing pathology apart from the appendix within the
right iliac fossa. The purpose of this pictorial essay is to highlight the
importance and value of performing a careful evaluation of the cecum during GCS
of patients with suspected appendicitis and to review the differential diagnosis
and imaging findings of primary cecal abnormalities whose clinical presentations
can mimic that of acute appendicitis.
PMID- 29346267
TI - Erratum: Lavergne, S.N. In Vitro Research Tools in the Field of Human Immediate
Drug Hypersensitivity and Their Present Use in Small Animal Veterinary Medicine
Vet. Sci. 2017, 4, 1.
AB - Due to an error during production, the author, Lavergne S. Lavergne's name in the
published paper [1] was incorrect.[...].
PMID- 29346266
TI - The Relationship between Autism Spectrum Disorder and Melatonin during Fetal
Development.
AB - The aim of this review is to clarify the interrelationship between melatonin and
autism spectrum disorder (ASD) during fetal development. ASD refers to a diverse
range of neurodevelopmental disorders characterized by social deficits, impaired
communication, and stereotyped or repetitive behaviors. Melatonin, which is
secreted by the pineal gland, has well-established neuroprotective and circadian
entraining effects. During pregnancy, the hormone crosses the placenta into the
fetal circulation and transmits photoperiodic information to the fetus allowing
the establishment of normal sleep patterns and circadian rhythms that are
essential for normal neurodevelopment. Melatonin synthesis is frequently impaired
in patients with ASD. The hormone reduces oxidative stress, which is harmful to
the central nervous system. Therefore, the neuroprotective and circadian
entraining roles of melatonin may reduce the risk of neurodevelopmental disorders
such as ASD.
PMID- 29346265
TI - Halfway between 2D and Animal Models: Are 3D Cultures the Ideal Tool to Study
Cancer-Microenvironment Interactions?
AB - An area that has come to be of tremendous interest in tumor research in the last
decade is the role of the microenvironment in the biology of neoplastic diseases.
The tumor microenvironment (TME) comprises various cells that are collectively
important for normal tissue homeostasis as well as tumor progression or
regression. Seminal studies have demonstrated the role of the dialogue between
cancer cells (at many sites) and the cellular component of the microenvironment
in tumor progression, metastasis, and resistance to treatment. Using an
appropriate system of microenvironment and tumor culture is the first step
towards a better understanding of the complex interaction between cancer cells
and their surroundings. Three-dimensional (3D) models have been widely described
recently. However, while it is claimed that they can bridge the gap between in
vitro and in vivo, it is sometimes hard to decipher their advantage or limitation
compared to classical two-dimensional (2D) cultures, especially given the broad
number of techniques used. We present here a comprehensive review of the
different 3D methods developed recently, and, secondly, we discuss the pros and
cons of 3D culture compared to 2D when studying interactions between cancer cells
and their microenvironment.
PMID- 29346268
TI - Effect of Novel Quercetin Titanium Dioxide-Decorated Multi-Walled Carbon
Nanotubes Nanocomposite on Bacillus subtilis Biofilm Development.
AB - The present work was targeted to design a surface against cell seeding and
adhering of bacteria, Bacillus subtilis. A multi-walled carbon nanotube/titanium
dioxide nano-power was produced via simple mixing of carbon nanotube and titanium
dioxide nanoparticles during the sol-gel process followed by heat treatment.
Successfully, quercetin was immobilized on the nanocomposite via physical
adsorption to form a quercetin/multi-walled carbon nanotube/titanium dioxide
nanocomposite. The adhesion of bacteria on the coated-slides was verified after
24 h using confocal laser-scanning microscopy. Results indicated that the
quercetin/multi-walled carbon nanotube/titanium dioxide nanocomposite had more
negativity and higher recovery by glass surfaces than its counterpart. Moreover,
coating surfaces with the quercetin-modified nanocomposite lowered both
hydrophilicity and surface-attached bacteria compared to surfaces coated with the
multi-walled carbon nanotubes/titanium dioxide nanocomposite.
PMID- 29346270
TI - Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations.
AB - The use of integrase inhibitors (INI) is increasing in antiretroviral therapies
(ART) and INI are not all equal regarding genetic barrier to resistance. The aim
of this manuscript was to review main in vivo and in vitro knowledge about two
particular integrase resistance-associated mutations: R263K and E157Q. The R263K
mutation was the first mutation rarely found selected at time of virological
failure in patients failing a first-line dolutegravir-based treatment. Further in
vitro studies on R263K mutants showed a moderate increase in phenotypic
resistance level and a drastic reduction in viral replicative capacity. No
compensatory mutations were evidenced. The E157Q mutation is polymorphic, found
between 1.7% and 5.6% of viral sequences issued from ART-naive patients depending
on the viral subtype; as well as acquired resistance emerging at failure of a
raltegravir-based regimen in two case reports. We reported data on phenotypic
resistance level of E157Q mutants and virological response of patients harboring
a E157Q virus initiating an INI-based regimen, showing that dolutegravir might be
the most recommended INI in such patients. These findings show that there is
still a need for a better understanding of resistance mechanisms to INI and
emphasized the importance of genotypic background in viral evolution under drug
pressure.
PMID- 29346271
TI - "Bacterial Toxins" Section in the Journal Toxins: A Fantastic Multidisciplinary
Interplay between Bacterial Pathogenicity Mechanisms, Physiological Processes,
Genomic Evolution, and Subsequent Development of Identification Methods,
Efficient Treatment, and Prevention of Toxigenic Bacteria.
AB - Toxins are powerful pathogenicity factors produced by certain bacteria, fungi,
animals, and plants which mediate drastic interactions of these pathogens on the
organism host[...].
PMID- 29346269
TI - Identification of Secreted Proteins Involved in Nonspecific dsRNA-Mediated
Lutzomyia longipalpis LL5 Cell Antiviral Response.
AB - Hematophagous insects transmit infectious diseases. Sand flies are vectors of
leishmaniasis, but can also transmit viruses. We have been studying immune
responses of Lutzomyia longipalpis, the main vector of visceral leishmaniasis in
the Americas. We identified a non-specific antiviral response in L. longipalpis
LL5 embryonic cells when treated with non-specific double-stranded RNAs (dsRNAs).
This response is reminiscent of interferon response in mammals. We are
investigating putative effectors for this antiviral response. Secreted molecules
have been implicated in immune responses, including interferon-related responses.
We conducted a mass spectrometry analysis of conditioned medium from LL5 cells 24
and 48 h after dsRNA or mock treatment. We identified 304 proteins. At 24 h, 19
proteins had an abundance equal or greater than 2-fold change, while the levels
of 17 proteins were reduced when compared to control cells. At the 48 h time
point, these numbers were 33 and 71, respectively. The two most abundant secreted
peptides at 24 h in the dsRNA-transfected group were phospholipid scramblase, an
interferon-inducible protein that mediates antiviral activity, and forskolin
binding protein (FKBP), a member of the immunophilin family, which mediates the
effect of immunosuppressive drugs. The transcription profile of most candidates
did not follow the pattern of secreted protein abundance.
PMID- 29346272
TI - Viral and Antibody Kinetics, and Mosquito Infectivity of an Imported Case of Zika
Fever Due to Asian Genotype (American Strain) in Singapore.
AB - We report a case of a Singaporean who acquired Zika virus (ZIKV) during a visit
to Cuba. The infection was confirmed using molecular and serological methods.
This report highlights potential drawbacks of using IgG serology for diagnosis of
flavivirus infections in endemic regions. The low viremia detected during the
early phase of this case resulted in low mosquito infectivity rates, suggesting
the possibility of ZIKV transmission prior to clinical onset. The report also
emphasizes the challenges of public health interventions for Zika fever and the
importance of sustaining a low vector population to reduce the risk of arbovirus
transmission in vulnerable regions.
PMID- 29346273
TI - Report on the Symposium "Molecular Mechanisms Involved in Neurodegeneration".
AB - The prevalence of neurodegenerative diseases is currently a major concern in
public health because of the lack of neuroprotective and neuroregenerative drugs.
The symposium on Molecular Mechanisms Involved in Neurodegeneration held in
Varadero, Cuba, updated the participants on the basic mechanisms of
neurodegeneration, on the different approaches for drug discovery, and on early
research results on therapeutic approaches for the treatment of neurodegenerative
diseases. Alzheimer's disease and in silico research were covered by many of the
presentations in the symposium, under the umbrella of the "State of the Art of
Non-clinical Models for Neurodegenerative Diseases" International Congress, held
from 20 to 24 June 2017. This paper summarizes the highlights of the symposium.
PMID- 29346274
TI - IRF4 Mediates the Oncogenic Effects of STAT3 in Anaplastic Large Cell Lymphomas.
AB - Systemic anaplastic large cell lymphomas (ALCL) are a category of T-cell non
Hodgkin's lymphomas which can be divided into anaplastic lymphoma kinase (ALK)
positive and ALK negative subgroups, based on ALK gene rearrangements. Among
several pathways aberrantly activated in ALCL, the constitutive activation of
signal transducer and activator of transcription 3 (STAT3) is shared by all ALK
positive ALCL and has been detected in a subgroup of ALK negative ALCL. To
discover essential mediators of STAT3 oncogenic activity that may represent
feasible targets for ALCL therapies, we combined gene expression profiling
analysis and RNA interference functional approaches. A shRNA screening of STAT3
modulated genes identified interferon regulatory factor 4 (IRF4) as a key driver
of ALCL cell survival. Accordingly, ectopic IRF4 expression partially rescued
STAT3 knock-down effects. Treatment with immunomodulatory drugs (IMiDs) induced
IRF4 down regulation and resulted in cell death, a phenotype rescued by IRF4
overexpression. However, the majority of ALCL cell lines were poorly responsive
to IMiDs treatment. Combination with JQ1, a bromodomain and extra-terminal (BET)
family antagonist known to inhibit MYC and IRF4, increased sensitivity to IMiDs.
Overall, these results show that IRF4 is involved in STAT3-oncogenic signaling
and its inhibition provides alternative avenues for the design of
novel/combination therapies of ALCL.
PMID- 29346276
TI - Comparison of the Response of Male BALB/c and C57BL/6 Mice in Behavioral Tasks to
Evaluate Cognitive Function.
AB - To evaluate several cognitive parameters during the execution of behavioral tasks
assessing cognitive function in laboratory animals, the parameters are reported
within a range. This situation entails that each laboratory must establish the
conditions under which the behavioral task to evaluate the cognitive function can
be carried out. C57BL/6 and BALB/c inbred strains are used more often in
behavioral studies relating to anxiety, stress, fear and cognitive function. The
aim of this work was to compare the behavioral response of mice of the strains
BALB/c and C57BL/6 to evaluate memory and learning as cognitive functions. Young
male mice, 7-8 weeks of age, from each strain were used. Y maze, object
recognition and passive avoidance tasks were performed. Both strains of mice
showed differences in the response to the passive avoidance and Y maze task. This
study advances knowledge about the baseline behavior of laboratory mice strains
and their response during the experimental procedures, which are due to the
treatment, genetic influence, procedural differences, genetic background
variance, or any combination of these elements.
PMID- 29346275
TI - A Review on Recent Advances in Stabilizing Peptides/Proteins upon Fabrication in
Hydrogels from Biodegradable Polymers.
AB - Hydrogels evolved as an outstanding carrier material for local and controlled
drug delivery that tend to overcome the shortcomings of old conventional dosage
forms for small drugs (NSAIDS) and large peptides and proteins. The aqueous
swellable and crosslinked polymeric network structure of hydrogels is composed of
various natural, synthetic and semisynthetic biodegradable polymers. Hydrogels
have remarkable properties of functionality, reversibility, sterilizability, and
biocompatibility. All these dynamic properties of hydrogels have increased the
interest in their use as a carrier for peptides and proteins to be released
slowly in a sustained manner. Peptide and proteins are remarkable therapeutic
agents in today's world that allow the treatment of severe, chronic and life
threatening diseases, such as diabetes, rheumatoid arthritis, hepatitis. Despite
few limitations, hydrogels provide fine tuning of proteins and peptides delivery
with enormous impact in clinical medicine. Novels drug delivery systems composed
of smart peptides and molecules have the ability to drive self-assembly and form
hydrogels at physiological pH. These hydrogels are significantly important for
biological and medical fields. The primary objective of this article is to review
current issues concerned with the therapeutic peptides and proteins and impact of
remarkable properties of hydrogels on these therapeutic agents. Different routes
for pharmaceutical peptides and proteins and superiority over other drugs
candidates are presented. Recent advances based on various approaches like self
assembly of peptides and small molecules to form novel hydrogels are also
discussed. The article will also review the literature concerning the
classification of hydrogels on a different basis, polymers used, "release
mechanisms" their physical and chemical characteristics and diverse applications.
PMID- 29346278
TI - A Case Study in Citizen Science: The Effectiveness of a Trap-Neuter-Return
Program in a Chicago Neighborhood.
AB - The use of trap-neuter-return (TNR) as a method of managing free-roaming cat
populations has increased in the United States in recent decades. Historically,
TNR has been conducted most often at a grassroots level, which has led to
inconsistent data collection and assessment practices. Consequently, a paucity of
analyzable data exists. An initiative is underway to standardize TNR program data
collection and assessment. However, it could be some time before scientifically
sound protocols are implemented on a broad scale. In the interim, sets of data
collected by nascent citizen scientists offer valid opportunities to evaluate
grassroots TNR programs. The purpose of the present study was to examine the
effectiveness of a TNR program conducted by a citizen scientist located in
Chicago, Illinois, where a county law permitting TNR was enacted in 2007. Colony
populations, when grouped by the number of years enrolled in the program,
declined by a mean of 54% from entry and 82% from peak levels. Results from
coexistent TNR programs in the Chicago area are consistent with these findings.
PMID- 29346277
TI - Vaccinia Virus in Blood Samples of Humans, Domestic and Wild Mammals in Brazil.
AB - Outbreaks of Vaccinia virus (VACV) affecting cattle and humans have been reported
in Brazil in the last 15 years, but the origin of outbreaks remains unknown.
Although VACV DNA have been already detected in mice (Mus musculus), opossums
(Didelphis albiventris) and dogs during VACV zoonotic outbreaks, no transmission
to cattle or humans from any of these were reported during Brazilian outbreaks.
In this work, we assessed the PCR positivity to VACV in blood samples of cows and
other domestic mammals, wild rodents and other wild mammals, and humans from
areas with or without VACV infection reports. Our results show the detection of
VACV DNA in blood samples of cows, horse and opossums, raising important
questions about VACV spread.
PMID- 29346279
TI - How Neighborhood Effects Vary: Childbearing and Fathering among Latino and
African American Adolescents.
AB - This study examines what neighborhood conditions experienced at age 15 and after
are associated with teen childbearing and fathering among Latino and African
American youth and whether these neighborhood effects vary by gender and/or
ethnicity. Administrative and survey data from a natural experiment are used for
a sample of 517 Latino and African American youth whose families were quasi
randomly assigned to public housing operated by the Denver (CO) Housing Authority
(DHA). Characteristics of the neighborhood initially assigned by DHA to wait list
applicants are utilized as identifying instruments for the neighborhood contexts
experienced during adolescence. Cox Proportional Hazards (PH) models reveal that
neighborhoods having higher percentages of foreign-born residents but lower
levels of social capital robustly predict reduced odds of teen parenting though
the magnitude of these effects was contingent on gender and ethnicity.
Specifically, the presence of foreign-born neighbors on the risk of teen
parenting produced a stronger dampening effect for African American youth when
compared to Latino youth. Additionally, the effects of social capital on teen
parenting were stronger for males than females.
PMID- 29346280
TI - A Multi-Band Body-Worn Distributed Radio-Frequency Exposure Meter: Design, On
Body Calibration and Study of Body Morphology.
AB - A multi-band Body-Worn Distributed exposure Meter (BWDM) calibrated for
simultaneous measurement of the incident power density in 11 telecommunication
frequency bands, is proposed. The BDWM consists of 22 textile antennas integrated
in a garment and is calibrated on six human subjects in an anechoic chamber to
assess its measurement uncertainty in terms of 68% confidence interval of the on
body antenna aperture. It is shown that by using multiple antennas in each
frequency band, the uncertainty of the BWDM is 22 dB improved with respect to
single nodes on the front and back of the torso and variations are decreased to
maximum 8.8 dB. Moreover, deploying single antennas for different body
morphologies results in a variation up to 9.3 dB, which is reduced to 3.6 dB
using multiple antennas for six subjects with various body mass index values. The
designed BWDM, has an improved uncertainty of up to 9.6 dB in comparison to
commercially available personal exposure meters calibrated on body. As an
application, an average incident power density in the range of 26.7-90.8 MUW.m -
2 is measured in Ghent, Belgium. The measurements show that commercial personal
exposure meters underestimate the actual exposure by a factor of up to 20.6.
PMID- 29346281
TI - A Prototype Sensor for In Situ Sensing of Fine Particulate Matter and Volatile
Organic Compounds.
AB - Air pollution exposure causes seven million deaths per year, according to the
World Health Organization. Possessing knowledge of air quality and sources of air
pollution is crucial for managing air pollution and providing early warning so
that a swift counteractive response can be carried out. An optical prototype
sensor (AtmOptic) capable of scattering and absorbance measurements has been
developed to target in situ sensing of fine particulate matter (PM2.5) and
volatile organic compounds (VOCs). For particulate matter testing, a test chamber
was constructed and the emission of PM2.5 from incense burning inside the chamber
was measured using the AtmOptic. The weight of PM2.5 particles was collected and
measured with a filter to determine their concentration and the sensor signal-to
concentration correlation. The results of the AtmOptic were also compared and
found to trend well with the Dylos DC 1100 Pro air quality monitor. The
absorbance spectrum of VOCs emitted from various laboratory chemicals and
household products as well as a two chemical mixtures were recorded. The
quantification was demonstrated, using toluene as an example, by calibrating the
AtmOptic with compressed gas standards containing VOCs at different
concentrations. The results demonstrated the sensor capabilities in measuring
PM2.5 and volatile organic compounds.
PMID- 29346282
TI - Smartphone-Based Cooperative Indoor Localization with RFID Technology.
AB - In GPS-denied indoor environments, localization and tracking of people can be
achieved with a mobile device such as a smartphone by processing the received
signal strength (RSS) of RF signals emitted from known location beacons (anchor
nodes), combined with Pedestrian Dead Reckoning (PDR) estimates of the user
motion. An enhacement of this localization technique is feasible if the users
themselves carry additional RF emitters (mobile nodes), and the cooperative
position estimates of a group of persons incorporate the RSS measurements
exchanged between users. We propose a centralized cooperative particle filter
(PF) formulation over the joint state of all users that permits to process RSS
measurements from both anchor and mobile emitters, as well as PDR motion
estimates and map information (if available) to increase the overall positioning
accuracy, particularly in regions with low density of anchor nodes. Smartphones
are used as a convenient mobile platform for sensor measurements acquisition, low
level processing, and data transmission to a central unit, where cooperative
localization processing takes place. The cooperative method is experimentally
demonstrated with four users moving in an area of 1600 m 2 , with 7 anchor nodes
comprised of active RFID (radio frequency identification) tags, and additional
mobile tags carried by each user. Due to the limited coverage provided by the
anchor beacons, RSS-based individual localization is inaccurate (6.1 m median
error), but this improves to 4.9 m median error with the cooperative PF. Further
gains are produced if the PDR information is added to the filter: median error of
3.1 m (individual) and 2.6 m (cooperative); and if map information is also
considered, the results are 1.8 m (individual) and 1.6 m (cooperative). Thus, for
each version of the particle filter, cooperative localization outperforms
individual localization in terms of positioning accuracy.
PMID- 29346283
TI - The Biological Role of Hyaluronan-Rich Oocyte-Cumulus Extracellular Matrix in
Female Reproduction.
AB - Fertilization of the mammalian oocyte requires interactions between spermatozoa
and expanded cumulus extracellular matrix (ECM) that surrounds the oocyte. This
review focuses on key molecules that play an important role in the formation of
the cumulus ECM, generated by the oocyte-cumulus complex. In particular, the
specific inhibitors (AG1478, lapatinib, indomethacin and MG132) and progesterone
receptor antagonist (RU486) exerting their effects through the remodeling of the
ECM of the cumulus cells surrounding the oocyte have been described. After
gonadotropin stimulus, cumulus cells expand and form hyaluronan (HA)-rich cumulus
ECM. In pigs, the proper structure of the cumulus ECM depends on the interaction
between HA and serum-derived proteins of the inter-alpha-trypsin inhibitor
(IalphaI) protein family. We have demonstrated the synthesis of HA by cumulus
cells, and the presence of the IalphaI, tumor necrosis factor-alpha-induced
protein 6 and pentraxin 3 in expanding oocyte-cumulus complexes (OCC). We have
evaluated the covalent linkage of heavy chains of IalphaI proteins to HA, as the
principal component of the expanded HA-rich cumulus ECM, in porcine OCC cultured
in medium with specific inhibitors: AG1478 and lapatinib (both inhibitors of
epidermal growth factor receptor tyrosine kinase activity); MG132 (a specific
proteasomal inhibitor), indomethacin (cyclooxygenase inhibitor); and progesterone
receptor antagonist (RU486). We have found that both RU486 and indomethacin does
not disrupt the formation of the covalent linkage between the heavy chains of
IalphaI to HA in the expanded OCC. In contrast, the inhibitors AG1478 and
lapatinib prevent gonadotropin-induced cumulus expansion. Finally, the formation
of oocyte-cumulus ECM relying on the covalent transfer of heavy chains of IalphaI
molecules to HA has been inhibited in the presence of MG132.
PMID- 29346284
TI - Double Heterozygosity for BRCA1 Pathogenic Variant and BRCA2 Polymorphic Stop
Codon K3326X: A Case Report in a Southern Italian Family.
AB - Here, we describe a patient with bilateral breast cancer and melanoma, and with a
concomitant double variant, namely p.Gln563Ter in BRCA1 and p.Lys3326Ter in
BRCA2. The BRCA2 p.Lys3326Ter (K3326X) (rs11571833) mutation identified in our
patient is a debated substitution of thymidine for adenine which is currently
regarded as benign polymorphism in main gene databases. Recent studies, however,
describe this variant as associated with breast and ovarian tumors. Based on the
observation of the cancer's earliest age of onset in this subject, our purpose
was to reevaluate this variant according to recent papers indicating a role of
powerful modifier of the genetic penetrance. Genetic testing was performed in all
consenting patient's relatives, and in the collection of the clinical data
particular attention was paid to the age of onset of the neoplasia. Following our
observation that the our patient with double heterozygosis had an early age of
onset for cancer similar to a few rare cases of double mutation for BRCA1 and
BRCA2, we also performed an extensive review of the literature relative to
patients carrying a double heterozygosity for both genes. In line with previous
studies relative to the rare double heterozygosity in both BRCA1/2 genes, we
found the earlier onset of breast cancer in our patient with both BRCA1/2
mutations with respect to other relatives carrying the single BRCA1 mutation. The
presence of the second K3326X variant in our case induces a phenotype
characterized by early onset of the neoplasia in a manner similar to the other
cases of double heterozygosity previously described. Therefore, we suggest that
during the genetic counseling, it should be recommendable to evaluate the
presence of the K3326X variant in association with other pathogenic mutations.
PMID- 29346285
TI - Characterization of Odors of Wood by Gas Chromatography-Olfactometry with Removal
of Extractives as Attempt to Control Indoor Air Quality.
AB - Indoor air quality problems are usually revealed by occupants' complaints. In
this study, the odors of two types of hardwood species, namely, Cathy poplar
(Populus cathayana Rehd.) and rubberwood (Hevea brasiliensis) were selected and
extracted with ethanol-toluene for removal of extractives in an attempt to
eliminate the odors. The odorous components of neat and extracted woods were
identified by gas chromatography-mass spectrometry/olfactometry (GC-MS/O). The
results showed that about 33 kinds of key volatile compounds (peak area above
0.2%) were detected from the GC-MS, and about 40 kinds of odorants were
identified from GC-O. The components were concentrated between 15 and 33 min in
GC-O, which was different from the concentration time in GC-MS. Lots of the odors
identified from GC-O were unpleasant to humans, and variously described as
stinky, burnt, leather, bug, herb, etc. These odors may originate from the
thermos-oxidation of wood components. After extraction, the amounts and
intensities of some odorants decreased, while some remained. However, the
extraction process resulted in a benzene residue and led to increased benzene
odor.
PMID- 29346286
TI - A More Efficient Transportable and Scalable System for Real-Time Activities and
Exercises Recognition.
AB - Many people in the world are affected by muscle wasting, especially the
population hits by myotonic dystrophy type 1 (DM1). Those people are usually
given a program of multiple physical exercises to do. While DM1 and many other
people have difficulties attending commercial centers to realize their program, a
solution is to develop such a program completable at home. To this end, we
developed a portable system that patients could bring home. This prototype is an
improved version of the previous one using Wi-Fi, as this new prototype runs on
BLE technology. This new prototype conceptualized induces great results.
PMID- 29346287
TI - Development of Zika Virus Vaccines.
AB - Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged as a global threat
following the most recent outbreak in Brazil in 2015. ZIKV infection of pregnant
women is associated with fetal abnormalities such as microcephaly, and infection
of adults can lead to Guillain-Barre syndrome, an autoimmune disease
characterized by neurological deficits. Although there are currently licensed
vaccines for other flaviviruses, there remains an urgent need for preventative
vaccines against ZIKV infection. Herein we describe the current efforts to
accelerate the development of ZIKV vaccines using various platforms, including
live attenuated virus, inactivated virus, DNA and RNA, viral vectors, and in
silico-predicted immunogenic viral epitopes. Many of these approaches have
leveraged lessons learned from past experience with Dengue and other flavivirus
vaccines.
PMID- 29346288
TI - Application of Computational Intelligence to Improve Education in Smart Cities.
AB - According to UNESCO, education is a fundamental human right and every nation's
citizens should be granted universal access with equal quality to it. Because
this goal is yet to be achieved in most countries, in particular in the
developing and underdeveloped countries, it is extremely important to find more
effective ways to improve education. This paper presents a model based on the
application of computational intelligence (data mining and data science) that
leads to the development of the student's knowledge profile and that can help
educators in their decision making for best orienting their students. This model
also tries to establish key performance indicators to monitor objectives'
achievement within individual strategic planning assembled for each student. The
model uses random forest for classification and prediction, graph description for
data structure visualization and recommendation systems to present relevant
information to stakeholders. The results presented were built based on the real
dataset obtained from a Brazilian private k-9 (elementary school). The obtained
results include correlations among key data, a model to predict student
performance and recommendations that were generated for the stakeholders.
PMID- 29346289
TI - Himawari-8 Satellite Based Dynamic Monitoring of Grassland Fire in China-Mongolia
Border Regions.
AB - In this study, we used bands 7, 4, and 3 of the Advance Himawari Imager (AHI)
data, combined with a Threshold Algorithm and a visual interpretation method to
monitor the entire process of grassland fires that occurred on the China-Mongolia
border regions, between 05:40 (UTC) on April 19th to 13:50 (UTC) on April 21st
2016. The results of the AHI data monitoring are evaluated by the fire point
product data, the wind field data, and the environmental information data of the
area in which the fire took place. The monitoring result shows that, the
grassland fire burned for two days and eight hours with a total burned area of
about 2708.29 km2. It mainly spread from the northwest to the southeast, with a
maximum burning speed of 20.9 m/s, a minimum speed of 2.52 m/s, and an average
speed of about 12.07 m/s. Thus, using AHI data can not only quickly and
accurately track the dynamic development of a grassland fire, but also estimate
the spread speed and direction. The evaluation of fire monitoring results reveals
that AHI data with high precision and timeliness can be highly consistent with
the actual situation.
PMID- 29346290
TI - Joint Probabilistic Data Association Filter with Unknown Detection Probability
and Clutter Rate.
AB - This paper proposes a novel joint probabilistic data association (JPDA) filter
for joint target tracking and track maintenance under unknown detection
probability and clutter rate. The proposed algorithm consists of two main parts:
(1) the standard JPDA filter with a Poisson point process birth model for multi
object state estimation; and (2) a multi-Bernoulli filter for detection
probability and clutter rate estimation. The performance of the proposed JPDA
filter is evaluated through empirical tests. The results of the empirical tests
show that the proposed JPDA filter has comparable performance with ideal JPDA
that is assumed to have perfect knowledge of detection probability and clutter
rate. Therefore, the algorithm developed is practical and could be implemented in
a wide range of applications.
PMID- 29346291
TI - Filaments Production and Fused Deposition Modelling of ABS/Carbon Nanotubes
Composites.
AB - Composite acrylonitrile-butadiene-styrene (ABS)/carbon nanotubes (CNT) filaments
at 1, 2, 4, 6 and 8 wt %, suitable for fused deposition modelling (FDM) were
obtained by using a completely solvent-free process based on direct melt
compounding and extrusion. The optimal CNT content in the filaments for FDM was
found to be 6 wt %; for this composite, a detailed investigation of the thermal,
mechanical and electrical properties was performed. Presence of CNT in ABS
filaments and 3D-printed parts resulted in a significant enhancement of the
tensile modulus and strength, accompanied by a reduction of the elongation at
break. As documented by dynamic mechanical thermal analysis, the stiffening
effect of CNTs in ABS is particularly pronounced at high temperatures. Besides,
the presence of CNT in 3D-printed parts accounts for better creep and thermal
dimensional stabilities of 3D-printed parts, accompanied by a reduction of the
coefficient of thermal expansion). 3D-printed nanocomposite samples with 6 wt %
of CNT exhibited a good electrical conductivity, even if lower than pristine
composite filaments.
PMID- 29346292
TI - Isoform Sequencing and State-of-Art Applications for Unravelling Complexity of
Plant Transcriptomes.
AB - Single-molecule real-time (SMRT) sequencing developed by PacBio, also called
third-generation sequencing (TGS), offers longer reads than the second-generation
sequencing (SGS). Given its ability to obtain full-length transcripts without
assembly, isoform sequencing (Iso-Seq) of transcriptomes by PacBio is
advantageous for genome annotation, identification of novel genes and isoforms,
as well as the discovery of long non-coding RNA (lncRNA). In addition, Iso-Seq
gives access to the direct detection of alternative splicing, alternative
polyadenylation (APA), gene fusion, and DNA modifications. Such applications of
Iso-Seq facilitate the understanding of gene structure, post-transcriptional
regulatory networks, and subsequently proteomic diversity. In this review, we
summarize its applications in plant transcriptome study, specifically pointing
out challenges associated with each step in the experimental design and highlight
the development of bioinformatic pipelines. We aim to provide the community with
an integrative overview and a comprehensive guidance to Iso-Seq, and thus to
promote its applications in plant research.
PMID- 29346293
TI - Fabry-Perot Interferometric High-Temperature Sensing Up to 1200 degrees C Based
on a Silica Glass Photonic Crystal Fiber.
AB - A Fabry-Perot interferometric sensor for temperature measurement was fabricated
based on a silica glass solid-core photonic crystal fiber with a central air
bore. By splicing a stub of photonic crystal fiber to a standard single-mode
fiber, an intrinsic Fabry-Perot cavity was formed inside the photonic crystal
fiber. Sensing experiment results show that the sensor can work stably for a
consecutive 24 h under temperatures up to 1100 degrees C, and the short-term
operation temperature can reach as high as 1200 degrees C (<30 min). In the
measurement range of 300-1200 degrees C, the temperature sensitivity of the peak
wavelength shift can reach as high as 15.61 pm/ degrees C, with a linearity of
99.76%. The presented interferometric sensor is compact in size and possesses
advantages such as an extended working range and high sensitivity, showing
promising application prospects.
PMID- 29346294
TI - GC-MS Analysis of the Volatile Constituents in the Leaves of 14 Compositae
Plants.
AB - The green organs, especially the leaves, of many Compositae plants possess
characteristic aromas. To exploit the utility value of these germplasm resources,
the constituents, mainly volatile compounds, in the leaves of 14 scented plant
materials were qualitatively and quantitatively compared via gas chromatography
mass spectrometry (GC-MS). A total of 213 constituents were detected and
tentatively identified in the leaf extracts, and terpenoids (especially
monoterpene and sesquiterpene derivatives), accounting for 40.45-90.38% of the
total compounds, were the main components. The quantitative results revealed
diverse concentrations and compositions of the chemical constituents between
species. Principal component analysis (PCA) showed that different groups of these
Compositae plants were characterized by main components of alpha-thujone,
germacrene D, eucalyptol, beta-caryophyllene, and camphor, for example. On the
other hand, cluster memberships corresponding to the molecular phylogenetic
framework, were found by hierarchical cluster analysis (HCA) based on the
terpenoid composition of the tested species. These results provide a
phytochemical foundation for the use of these scented Compositae plants, and for
the further study of the chemotaxonomy and differential metabolism of Compositae
species.
PMID- 29346295
TI - Peri-Elastodynamic Simulations of Guided Ultrasonic Waves in Plate-Like Structure
with Surface Mounted PZT.
AB - Peridynamic based elastodynamic computation tool named Peri-elastodynamics is
proposed herein to simulate the three-dimensional (3D) Lamb wave modes in
materials for the first time. Peri-elastodynamics is a nonlocal meshless approach
which is a scale-independent generalized technique to visualize the acoustic and
ultrasonic waves in plate-like structure, micro-electro-mechanical systems (MEMS)
and nanodevices for their respective characterization. In this article, the
characteristics of the fundamental Lamb wave modes are simulated in a sample
plate-like structure. Lamb wave modes are generated using a surface mounted
piezoelectric (PZT) transducer which is actuated from the top surface. The
proposed generalized Peri-elastodynamics method is not only capable of simulating
two dimensional (2D) in plane wave under plane strain condition formulated
previously but also capable of accurately simulating the out of plane Symmetric
and Antisymmetric Lamb wave modes in plate like structures in 3D. For structural
health monitoring (SHM) of plate-like structures and nondestructive evaluation
(NDE) of MEMS devices, it is necessary to simulate the 3D wave-damage interaction
scenarios and visualize the different wave features due to damages. Hence, in
addition, to simulating the guided ultrasonic wave modes in pristine material,
Lamb waves were also simulated in a damaged plate. The accuracy of the proposed
technique is verified by comparing the modes generated in the plate and the mode
shapes across the thickness of the plate with theoretical wave analysis.
PMID- 29346296
TI - Highly Sensitive Strain Sensor Based on a Novel Mach-Zehnder Interferometer with
TCF-PCF Structure.
AB - A highly sensitive strain sensor based on a novel fiber in line Mach-Zehnder
interferometer (MZI) was demonstrated experimentally. The MZI was realized by
splicing a section of photonic crystal fiber (PCF) with the same length of thin
core fiber (TCF) between two single mode fibers (SMFs). The fringe visibility of
MZI can reach as high as 20 dB in air. In particular, the strain sensitivity of
1.95 pm/MUepsilon was achieved within a range from 0 to 4000 MUepsilon.
Furthermore, the strain properties of different length of MZI was investigated.
It was found that the sensitivity was weekly dependent on the length of MZI. The
strain sensitivities corresponding to the MZI with 35 mm PCF, 40 mm PCF and 45 mm
PCF at 1550 nm band were -1.78 pm/MUepsilon, -1.73 pm/MUepsilon and -1.63
pm/MUepsilon, respectively. Additionally, the sensor has advantages of simple
fabrication, compact size and high sensitivity as well as good fringe visibility.
PMID- 29346297
TI - The Dynamic Performance of Flexural Ultrasonic Transducers.
AB - Flexural ultrasonic transducers are principally used as proximity sensors and for
industrial metrology. Their operation relies on a piezoelectric ceramic to
generate a flexing of a metallic membrane, which delivers the ultrasound signal.
The performance of flexural ultrasonic transducers has been largely limited to
excitation through a short voltage burst signal at a designated mechanical
resonance frequency. However, a steady-state amplitude response is not generated
instantaneously in a flexural ultrasonic transducer from a drive excitation
signal, and differences in the drive characteristics between transmitting and
receiving transducers can affect the measured response. This research
investigates the dynamic performance of flexural ultrasonic transducers using
acoustic microphone measurements and laser Doppler vibrometry, supported by a
detailed mechanical analog model, in a process which has not before been applied
to the flexural ultrasonic transducer. These techniques are employed to gain
insights into the physics of their vibration behaviour, vital for the
optimisation of industrial ultrasound systems.
PMID- 29346298
TI - Motion Tracking System for Robust Non-Contact Blood Perfusion Sensor.
AB - We propose a motion-robust laser Doppler flowmetry (LDF) system that can be used
as a non-contact blood perfusion sensor for medical diagnosis. Endoscopic LDF
systems are typically limited in their usefulness in clinical contexts by the
need for the natural organs to be immobilized, as serious motion artifacts due to
the axial surface displacement can interfere with blood perfusion measurements.
In our system, the focusing lens moves to track the motion of the target using a
low-frequency reference signal in the optical data, enabling the suppression of
these motion artifacts in the axial direction. This paper reports feasibility
tests on a prototype of this system using a microfluidic phantom as a measurement
target moving in the direction of the optical axis. The frequency spectra
detected and the perfusion values calculated from those spectra show that the
motion tracking system is capable of suppressing motion artifacts in perfusion
readings. We compared the prototype LDF system's measurements with and without
motion feedback, and found that motion tracking improves the fidelity of the
perfusion signal by as much as 87%.
PMID- 29346299
TI - Meteo and Hydrodynamic Measurements to Detect Physical Processes in Confined
Shallow Seas.
AB - Coastal sites with typical lagoon features are extremely vulnerable, often
suffering from scarce circulation. Especially in the case of shallow basins
subjected to strong anthropization and urban discharges, it is fundamental to
monitor their hydrodynamics and water quality. The proper detection of events by
high performance sensors and appropriate analysis of sensor signals has proved to
be a necessary tool for local authorities and stakeholders, leading to early
warning and preventive measures against environmental degradation and related
hazards. At the same time, assessed datasets are not only essential to deepen the
knowledge of the physical processes in the target basin, but are also necessary
to calibrate and validate modelling systems providing forecasts. The present
paper aims to show how long-term and continuous recordings of meteorological and
hydrodynamic data, collected in a semi-enclosed sea, can be managed to rapidly
provide fundamental insights on its hydrodynamic structure. The acquired signals
have been analyzed in time domain, processed and finally, correlated. The adopted
method is simple, feasible and easily replicable. Even if the results are site
dependent, the procedure is generic, and depends on having good quality available
data. To show how this might be employed, a case study is examined. In fact, it
has been applied to a coastal system, located in Southern Italy, where two
monitoring stations are placed in two interconnected basins. The inferred results
show that the system is not wind dominated, and that the annual trends in the
wind regime, wave spreading and current circulation are not independent, but
rather reiterate. These deductions are of great interest as a predictive
perspective and for numerical modelling.
PMID- 29346300
TI - Trapezium Bone Density-A Comparison of Measurements by DXA and CT.
AB - Bone density may influence the primary fixation of cementless implants, and poor
bone density may increase the risk of implant failure. Before deciding on using
total joint replacement as treatment in osteoarthritis of the trapeziometacarpal
joint, it is valuable to determine the trapezium bone density. The aim of this
study was to: (1) determine the correlation between measurements of bone mineral
density of the trapezium obtained by dual-energy X-ray absorptiometry (DXA) scans
by a circumference method and a new inner-ellipse method; and (2) to compare
those to measurements of bone density obtained by computerized tomography (CT)
scans in Hounsfield units (HU). We included 71 hands from 59 patients with a mean
age of 59 years (43-77). All patients had Eaton-Glickel stage II-IV
trapeziometacarpal (TM) joint osteoarthritis, were under evaluation for
trapeziometacarpal total joint replacement, and underwent DXA and CT wrist scans.
There was an excellent correlation (r = 0.94) between DXA bone mineral density
measures using the circumference and the inner-ellipse method. There was a
moderate correlation between bone density measures obtained by DXA- and CT-scans
with (r = 0.49) for the circumference method, and (r = 0.55) for the inner
ellipse method. DXA may be used in pre-operative evaluation of the trapezium bone
quality, and the simpler DXA inner-ellipse measurement method can replace the DXA
circumference method in estimation of bone density of the trapezium.
PMID- 29346302
TI - Smart Device-Based Notifications to Promote Healthy Behavior Related to Childhood
Obesity and Overweight.
AB - Obesity is one of the most serious public health challenges of the 21st century
and it is a threat to the life of people according to World Health Organization.
In this scenario, family environment is important to establish healthy habits
which help to reduce levels of obesity and control overweight in children.
However, little efforts have been focused on helping parents to promote and have
healthy lifestyles. In this paper, we present two smart device-based notification
prototypes to promote healthy behavior with the aim of avoiding childhood
overweight and obesity. The first prototype helps parents to follow a healthy
snack routine, based on a nutritionist suggestion. Using a fridge magnet, parents
receive graphical reminders of which snacks they and their children should
consume. The second prototype provides a graphical reminder that prevents parents
from forgetting the required equipment to practice sports. Prototypes were
evaluated by nine nutritionists from three countries (Costa Rica, Mexico and
Spain). Evaluations were based on anticipation of use and the ergonomics of human
system interaction according to the ISO 9241-210. Results show that the system is
considered useful. Even though they might not be willing to use the system, they
would recommend it to their patients. Based on the ISO 9241-210 the best ranked
features were the system's comprehensibility, the perceived effectiveness and
clarity. The worst ranked features were the system's suitability for learning and
its discriminability.
PMID- 29346301
TI - BRAF and MEK Inhibitors Influence the Function of Reprogrammed T Cells:
Consequences for Adoptive T-Cell Therapy.
AB - BRAF and MEK inhibitors (BRAFi/MEKi), the standard treatment for patients with
BRAFV600 mutated melanoma, are currently explored in combination with various
immunotherapies, notably checkpoint inhibitors and adoptive transfer of receptor
transfected T cells. Since two BRAFi/MEKi combinations with similar efficacy are
approved, potential differences in their effects on immune cells would enable a
rational choice for triple therapies. Therefore, we characterized the influence
of the clinically approved BRAFi/MEKi combinations dabrafenib (Dabra) and
trametinib (Tram) vs. vemurafenib (Vem) and cobimetinib (Cobi) on the activation
and functionality of chimeric antigen receptor (CAR)-transfected T cells. We co
cultured CAR-transfected CD8+ T cells and target cells with clinically relevant
concentrations of the inhibitors and determined the antigen-induced cytokine
secretion. All BRAFi/MEKi reduced this release as single agents, with Dabra
having the mildest inhibitory effect, and Dabra + Tram having a clearly milder
inhibitory effect than Vem + Cobi. A similar picture was observed for the
upregulation of the activation markers CD25 and CD69 on CAR-transfected T cells
after antigen-specific stimulation. Most importantly, the cytolytic capacity of
the CAR-T cells was significantly inhibited by Cobi and Vem + Cobi, whereas the
other kinase inhibitors showed no effect. Therefore, the combination Dabra + Tram
would be more suitable for combining with T-cell-based immunotherapy than Vem +
Cobi.
PMID- 29346303
TI - Micro-Spherical Sulfur/Graphene Oxide Composite via Spray Drying for High
Performance Lithium Sulfur Batteries.
AB - An efficient, industry-accepted spray drying method was used to synthesize micro
spherical sulfur/graphene oxide (S/GO) composites as cathode materials within
lithium sulfur batteries. The as-designed wrapping of the sulfur-nanoparticles,
with wrinkled GO composites, was characterized by scanning electron microscopy
(SEM) and transmission electron microscopy (TEM). The unique morphological design
of this material enabled superior discharge capacity and cycling performance,
demonstrating a high initial discharge capacity of 1400 mAh g-1 at 0.1 C. The
discharge capacity remained at 828 mAh g-1 after 150 cycles. The superior
electrochemical performance indicates that the S/GO composite improves electrical
conductivity and alleviates the shuttle effect. This study represents the first
time such a facile spray drying method has been adopted for lithium sulfur
batteries and used in the fabrication of S/GO composites.
PMID- 29346304
TI - 'Total Pain' in Children with Severe Neurological Impairment.
AB - Many children with palliative care needs experience difficulty in managing pain.
Perhaps none more so than those with severe neurological impairment. For many
years; behaviours in these children were misunderstood. As a result; pain was
poorly recognised and inadequately managed. Significant advances have been made
in the assessment and management of pain in this challenging group of patients.
We summarise these advances; drawing on our own experience working with infants;
children and young adults with palliative care needs within a UK tertiary
paediatric palliative care service. We expand on the recent understanding of
'Total Pain'; applying a holistic approach to pain assessment and management in
children with severe neurological impairment.
PMID- 29346305
TI - The Sustainable Development Assessment of Reservoir Resettlement Based on a BP
Neural Network.
AB - Resettlement affects not only the resettlers' production activities and life but
also, directly or indirectly, the normal operation of power stations, the
sustainable development of the resettlers, and regional social stability.
Therefore, a scientific evaluation index system for the sustainable development
of reservoir resettlement must be established that fits Chinese national
conditions and not only promotes reservoir resettlement research but also
improves resettlement practice. This essay builds an evaluation index system for
resettlers' sustainable development based on a back-propagation (BP) neural
network, which can be adopted in China, taking the resettlement necessitated by
step hydropower stations along the Wujiang River cascade as an example. The
assessment results show that the resettlement caused by step power stations along
the Wujiang River is sustainable, and this evaluation supports the conclusion
that national policies and regulations, which are undergoing constant
improvement, and resettlement has increasingly improved. The results provide a
reference for hydropower reservoir resettlement in developing countries.
PMID- 29346306
TI - Zinc Tantalum Oxynitride (ZnTaO2N) Photoanode Modified with Cobalt Phosphate
Layers for the Photoelectrochemical Oxidation of Alkali Water.
AB - Photoanodes fabricated by the electrophoretic deposition of a thermally prepared
zinc tantalum oxynitride (ZnTaO2N) catalyst onto indium tin oxide (ITO)
substrates show photoactivation for the oxygen evolution reaction (OER) in
alkaline solutions. The photoactivity of the OER is further boosted by the
photodeposition of cobalt phosphate (CoPi) layers onto the surface of the ZnTaO2N
photoanodes. Structural, morphological, and photoelectrochemical (PEC) properties
of the modified ZnTaO2N photoanodes are studied using X-ray diffraction (XRD),
scanning electron microscopy (SEM), ultraviolet visible (UV-Vis) diffuse
reflectance spectroscopy, and electrochemical techniques. The presence of the
CoPi layer significantly improved the PEC performance of water oxidation in an
alkaline sulphate solution. The photocurrent-voltage behavior of the CoPi
modified ZnTaO2N anodes was improved, with the influence being more prominent at
lower oxidation potentials. A stable photocurrent density of about 2.3 mA.cm-2 at
1.23 V vs. RHE was attained upon visible light illumination. Relative to the
ZnTaO2N photoanodes, an almost three-fold photocurrent increase was achieved at
the CoPi/ZnTaO2N photoelectrode. Perovskite-based oxynitrides are modified using
an oxygen-evolution co-catalyst of CoPi, and provide a new dimension for
enhancing the photoactivity of oxygen evolution in solar-assisted water-splitting
reactions.
PMID- 29346307
TI - Knowledge and Attitudes of General Practitioners and Sexual Health Care
Professionals Regarding Human Papillomavirus Vaccination for Young Men Who Have
Sex with Men.
AB - Men who have sex with men (MSM) may be at higher risk for human papillomavirus
(HPV)-associated cancers. Healthcare professionals' recommendations can affect
HPV vaccination uptake. Since 2016, MSM up to 45 years have been offered HPV
vaccination at genitourinary medicine (GUM) clinics in a pilot programme, and
primary care was recommended as a setting for opportunistic vaccination.
Vaccination prior to potential exposure to the virus (i.e., sexual debut) is
likely to be most efficacious, therefore a focus on young MSM (YMSM) is
important. This study aimed to explore and compare the knowledge and attitudes of
UK General Practitioners (GPs) and sexual healthcare professionals (SHCPs)
regarding HPV vaccination for YMSM (age 16-24). A cross-sectional study using an
online questionnaire examined 38 GPs and 49 SHCPs, including 59 (67.82%) females
with a mean age of 40.71 years. Twenty-two participants (20 SHCPs, p < 0.001) had
vaccinated a YMSM patient against HPV. GPs lack of time (25/38, 65.79%) and SHCP
staff availability (27/49, 55.10%) were the main reported factors preventing YMSM
HPV vaccination. GPs were less likely than SHCPs to believe there was sufficient
evidence for vaccinating YMSM (OR = 0.02, 95% CI = 0.01, 0.47); less likely to
have skills to identify YMSM who may benefit from vaccination (OR = 0.03, 95% CI
= 0.01, 0.15); and less confident recommending YMSM vaccination (OR = 0.01, 95%
CI = 0.00, 0.01). GPs appear to have different knowledge, attitudes, and skills
regarding YMSM HPV vaccination when compared to SHCPs.
PMID- 29346310
TI - AR Signaling in Human Malignancies: Prostate Cancer and Beyond.
AB - The notion that androgens and androgen receptor (AR) signaling are the hallmarks
of prostate cancer oncogenesis and disease progression is generally well
accepted. What is more poorly understood is the role of AR signaling in other
human malignancies. This special issue of Cancers initially reviews the role of
AR in advanced prostate cancer, and then explores the potential importance of AR
signaling in other epithelial malignancies. The first few articles focus on the
use of novel AR-targeting therapies in castration-resistant prostate cancer and
the mechanisms of resistance to novel antiandrogens, and they also outline the
interaction between AR and other cellular pathways, including PI3 kinase
signaling, transcriptional regulation, angiogenesis, stromal factors, Wnt
signaling, and epigenetic regulation in prostate cancer. The next several
articles review the possible role of androgens and AR signaling in breast cancer,
bladder cancer, salivary gland cancer, and hepatocellular carcinoma, as well as
the potential treatment implications of using antiandrogen therapies in these non
prostatic malignancies.
PMID- 29346308
TI - Tissue Engineering to Improve Immature Testicular Tissue and Cell Transplantation
Outcomes: One Step Closer to Fertility Restoration for Prepubertal Boys Exposed
to Gonadotoxic Treatments.
AB - Despite their important contribution to the cure of both oncological and benign
diseases, gonadotoxic therapies present the risk of a severe impairment of
fertility. Sperm cryopreservation is not an option to preserve prepubertal boys'
reproductive potential, as their seminiferous tubules only contain spermatogonial
stem cells (as diploid precursors of spermatozoa). Cryobanking of human immature
testicular tissue (ITT) prior to gonadotoxic therapies is an accepted practice.
Evaluation of cryopreserved ITT using xenotransplantation in nude mice showed the
survival of a limited proportion of spermatogonia and their ability to
proliferate and initiate differentiation. However, complete spermatogenesis could
not be achieved in the mouse model. Loss of germ cells after ITT grafting points
to the need to optimize the transplantation technique. Tissue engineering, a new
branch of science that aims at improving cellular environment using scaffolds and
molecules administration, might be an approach for further progress. In this
review, after summarizing the lessons learned from human prepubertal testicular
germ cells or tissue xenotransplantation experiments, we will focus on the
benefits that might be gathered using bioengineering techniques to enhance
transplantation outcomes by optimizing early tissue graft revascularization,
protecting cells from toxic insults linked to ischemic injury and exploring
strategies to promote cellular differentiation.
PMID- 29346309
TI - The Role of E6 Spliced Isoforms (E6*) in Human Papillomavirus-Induced
Carcinogenesis.
AB - Persistent infections with High Risk Human Papillomaviruses (HR-HPVs) are the
main cause of cervical cancer development. The E6 and E7 oncoproteins of HR-HPVs
are derived from a polycistronic pre-mRNA transcribed from an HPV early promoter.
Through alternative splicing, this pre-mRNA produces a variety of E6 spliced
transcripts termed E6*. In pre-malignant lesions and HPV-related cancers,
different E6/E6* transcriptional patterns have been found, although they have not
been clearly associated to cancer development. Moreover, there is a controversy
about the participation of E6* proteins in cancer progression. This review
addresses the regulation of E6 splicing and the different functions that have
been found for E6* proteins, as well as their possible role in HPV-induced
carcinogenesis.
PMID- 29346312
TI - Sidewalk Landscape Structure and Thermal Conditions for Child and Adult
Pedestrians.
AB - Walking is being promoted for health and transportation purposes across all
climatic regions in the US and beyond. Despite this, an uncomfortable
microclimate condition along sidewalks is one of the major deterrents of walking,
and more empirical research is needed to determine the risks of heat exposure to
pedestrians while walking. This study examined the effect of street trees and
grass along sidewalks on air temperatures. A series of thermal images were taken
at the average heights of adults and children in the US to objectively measure
the air temperatures of 10 sidewalk segments in College Station, TX, USA. After
controlling the other key physical environmental conditions, sidewalks with more
trees or wider grass buffer areas had lower air temperatures than those with less
vegetation. Children were exposed to higher temperatures due to the greater
exposure or proximity to the pavement surface, which tends to have higher radiant
heat. Multivariate regression analysis suggested that the configuration of trees
and grass buffers along the sidewalks helped to promote pleasant thermal
conditions and reduced the differences in ambient air temperatures measured at
child and adult heights. This study suggests that street trees and vegetated
ground help reduce the air temperatures, leading to more thermally comfortable
environments for both child and adult pedestrians in warm climates. The thermal
implications of street landscape require further attention by researchers and
policy makers that are interested in promoting outdoor walking.
PMID- 29346313
TI - A Comparison of the Chemical Composition, In Vitro Bioaccessibility and
Antioxidant Activity of Phenolic Compounds from Rice Bran and Its Dietary Fibres.
AB - The composition, in vitro bioaccessibility and antioxidant activities of the
phenolic compounds in defatted rice bran (DRB) and its soluble and insoluble
dietary fibres were systematically evaluated in this study. The total phenolic
content of insoluble dietary fibre from DRB (IDFDRB) was much higher than that of
the soluble dietary fibre from DRB (SDFDRB) but was 10% lower than that of DRB.
Bound phenolics accounted for more than 90% of the total phenolics in IDFDRB,
whereas they accounted for 34.2% and 40.5% of the total phenolics in DRB and
SDFDRB, respectively. Additionally, the phenolic profiles and antioxidant
activities were significantly different in DRB, SDFDRB and IDFDRB. The phenolic
compounds in IDFDRB were much less bioaccessibility than those in DRB and SDFDRB
due to the higher proportion of bound phenolics in IDFDRB. Considering that bound
phenolics could be released from food matrices by bacterial enzymes in the large
intestine and go on to exert significant beneficial health effects in vivo,
further studies on IDFDRB are needed to investigate the release of the phenolics
from IDFDRB via gut microbiota and the related health benefits.
PMID- 29346311
TI - Apoptotic and Nonapoptotic Activities of Pterostilbene against Cancer.
AB - Cancer is a major cause of death. The outcomes of current therapeutic strategies
against cancer often ironically lead to even increased mortality due to the
subsequent drug resistance and to metastatic recurrence. Alternative medicines
are thus urgently needed. Cumulative evidence has pointed out that pterostilbene
(trans-3,5-dimethoxy-4-hydroxystilbene, PS) has excellent pharmacological
benefits for the prevention and treatment for various types of cancer in their
different stages of progression by evoking apoptotic or nonapoptotic anti-cancer
activities. In this review article, we first update current knowledge regarding
tumor progression toward accomplishment of metastasis. Subsequently, we review
current literature regarding the anti-cancer activities of PS. Finally, we
provide future perspectives to clinically utilize PS as novel cancer therapeutic
remedies. We, therefore, conclude and propose that PS is one ideal alternative
medicine to be administered in the diet as a nutritional supplement.
PMID- 29346314
TI - Sustainable Transportation Attitudes and Health Behavior Change: Evaluation of a
Brief Stage-Targeted Video Intervention.
AB - Promoting physical activity and sustainable transportation is essential in the
face of rising health care costs, obesity rates, and other public health threats
resulting from lack of physical activity. Targeted communications can encourage
distinct population segments to adopt active and sustainable transportation
modes. Our work is designed to promote the health, social, and environmental
benefits of sustainable/active transportation (ST) using the Transtheoretical
Model of Change (TTM), which has been successfully applied to a range of health,
and more recently, sustainability behaviors. Earlier, measurement development
confirmed both the structure of ST pros and cons and efficacy measures as well as
the relationship between these constructs and ST stages of change, replicating
results found for many other behaviors. The present paper discusses a brief pre
post video pilot intervention study designed for precontemplators and
contemplators (N = 604) that was well received, effective in moving respondents
towards increased readiness for ST behavior change, and improving some ST
attitudes, significantly reducing the cons of ST. This research program shows
that a brief stage-targeted behavior change video can increase readiness and
reduce the cons for healthy transportation choices.
PMID- 29346315
TI - Dietary Total Prenylflavonoids from the Fruits of Psoralea corylifolia L.
Prevents Age-Related Cognitive Deficits and Down-Regulates Alzheimer's Markers in
SAMP8 Mice.
AB - Alzheimer's disease (AD) is a serious threat for the aging society. In this
study, we examined the preventive effect of the total prenylflavonoids (TPFB)
prepared from the dried fruits of Psoralea corylifolia L., using an age-related
AD mouse model SAMP8. We found that long-term dietary TPFB at 50 mg/kg.day
significantly improved cognitive performance of the SAMP8 mice in Morris water
maze tests, similar to 150 mg/kg.day of resveratrol, a popular neuro-protective
compound. Furthermore, TPFB treatment showed significant improvements in various
AD markers in SAMP8 brains, which were restored to near control levels of the
normal mice, SAMR1. TPFB significantly reduced the level of amyloid beta-peptide
42 (Abeta42), inhibited hyperphosphorylation of the microtubule-associated
protein Tau, induced phosphorylation of Ser9 of the glycogen synthase kinase
3beta (GSK-3beta), and decreased the expression of the proinflammatory cytokines
TNFalpha, IL-6, and IL-1beta. Finally, TPFB also markedly reduced the level of
serum derivatives of reactive oxygen metabolites (d-ROMs), a biomarker of
oxidative stress in vivo. These results showed that dietary TPFB could
effectively prevent age-related cognitive deficits and AD-like neurobiochemical
changes, and may have a potential role in the prevention of Alzheimer's disease.
PMID- 29346316
TI - Chronic Dietary Intake of Enniatin B in Broiler Chickens Has Low Impact on
Intestinal Morphometry and Hepatic Histology, and Shows Limited Transfer to Liver
Tissue.
AB - The Fusarium mycotoxin enniatin B (ENN B) is a so-called emerging mycotoxin
frequently contaminating poultry feed. To investigate the impact of chronic ENN B
exposure on animal health, broiler chickens were fed either a diet naturally
contaminated with ENN B (2352 ug/kg) or a control diet (135 ug/kg) for 2, 7, 14,
or 21 days. ENN B concentrations were determined in plasma and liver using a
validated ultra-high performance liquid chromatography-tandem mass spectrometry
UHPLC-MS/MS method. Liver was evaluated histologically, and the villus length and
crypt depth of the duodenum, jejunum, and ileum were measured. Histopathology of
the livers did not reveal major abnormalities. Feeding an ENN B-contaminated diet
could possibly inhibit the proliferation of enterocytes in the duodenal crypts,
but did not affect villus length, crypt depth, or villus length-crypt depth ratio
of the jejunum and ileum. ENN B levels in plasma and liver were significantly
higher in the ENN B-fed group and ranged between <25-264 pg/mL and <0.05-0.85
ng/g, respectively. ENN B carry-over rates from feed to liver tissue were 0.005
0.014% and 0.034-0.109% in the ENN B and control group, respectively. Carry-over
rates were low and indicated a limited contribution of poultry tissue-derived
products to the total dietary ENN B intake for humans. The above results support
the opinion of the European Food Safety Authority stating that adverse health
effects from ENN B in broiler chickens are unlikely.
PMID- 29346318
TI - Differences between Outdoor and Indoor Sound Levels for Open, Tilted, and Closed
Windows.
AB - Noise exposure prediction models for health effect studies normally estimate free
field exposure levels outside. However, to assess the noise exposure inside
dwellings, an estimate of indoor sound levels is necessary. To date, little field
data is available about the difference between indoor and outdoor noise levels
and factors affecting the damping of outside noise. This is a major cause of
uncertainty in indoor noise exposure prediction and may lead to exposure
misclassification in health assessments. This study aims to determine sound level
differences between the indoors and the outdoors for different window positions
and how this sound damping is related to building characteristics. For this
purpose, measurements were carried out at home in a sample of 102 Swiss residents
exposed to road traffic noise. Sound pressure level recordings were performed
outdoors and indoors, in the living room and in the bedroom. Three scenarios-of
open, tilted, and closed windows-were recorded for three minutes each. For each
situation, data on additional parameters such as the orientation towards the
source, floor, and room, as well as sound insulation characteristics were
collected. On that basis, linear regression models were established. The median
outdoor-indoor sound level differences were of 10 dB(A) for open, 16 dB(A) for
tilted, and 28 dB(A) for closed windows. For open and tilted windows, the most
relevant parameters affecting the outdoor-indoor differences were the position of
the window, the type and volume of the room, and the age of the building. For
closed windows, the relevant parameters were the sound level outside, the
material of the window frame, the existence of window gaskets, and the number of
windows.
PMID- 29346317
TI - Liposomal TriCurin, A Synergistic Combination of Curcumin, Epicatechin Gallate
and Resveratrol, Repolarizes Tumor-Associated Microglia/Macrophages, and
Eliminates Glioblastoma (GBM) and GBM Stem Cells.
AB - Glioblastoma (GBM) is a deadly brain tumor with a current mean survival of 12-15
months. Despite being a potent anti-cancer agent, the turmeric ingredient
curcumin (C) has limited anti-tumor efficacy in vivo due to its low
bioavailability. We have reported earlier a strategy involving the use two other
polyphenols, epicatechin gallate (E) from green tea and resveratrol (R) from red
grapes at a unique, synergistic molar ratio with C (C:E:R: 4:1:12.5, termed
TriCurin) to achieve superior potency against HPV+ tumors than C alone at C:E:R
(MUM): 32:8:100 (termed 32 MUM+ TriCurin). We have now prepared liposomal
TriCurin (TrLp) and demonstrated that TrLp boosts activated p53 in cultured GL261
mouse GBM cells to trigger apoptosis of GBM and GBM stem cells in vitro. TrLp
administration into mice yielded a stable plasma concentration of 210 nM C for 60
min, which, though sub-lethal for cultured GL261 cells, was able to cause
repolarization of M2-like tumor (GBM)-associated microglia/macrophages to the
tumoricidal M1-like phenotype and intra-GBM recruitment of activated natural
killer cells. The intratumor presence of such tumoricidal immune cells was
associated with concomitant suppression of tumor-load, and apoptosis of GBM and
GBM stem cells. Thus, TrLp is a potential onco-immunotherapeutic agent against
GBM tumors.
PMID- 29346319
TI - Hierarchical Discriminant Analysis.
AB - The Internet of Things (IoT) generates lots of high-dimensional sensor
intelligent data. The processing of high-dimensional data (e.g., data
visualization and data classification) is very difficult, so it requires
excellent subspace learning algorithms to learn a latent subspace to preserve the
intrinsic structure of the high-dimensional data, and abandon the least useful
information in the subsequent processing. In this context, many subspace learning
algorithms have been presented. However, in the process of transforming the high
dimensional data into the low-dimensional space, the huge difference between the
sum of inter-class distance and the sum of intra-class distance for distinct data
may cause a bias problem. That means that the impact of intra-class distance is
overwhelmed. To address this problem, we propose a novel algorithm called
Hierarchical Discriminant Analysis (HDA). It minimizes the sum of intra-class
distance first, and then maximizes the sum of inter-class distance. This proposed
method balances the bias from the inter-class and that from the intra-class to
achieve better performance. Extensive experiments are conducted on several
benchmark face datasets. The results reveal that HDA obtains better performance
than other dimensionality reduction algorithms.
PMID- 29346321
TI - New Control Paradigms for Resources Saving: An Approach for Mobile Robots
Navigation.
AB - In this work, an event-based control scheme is presented. The proposed system has
been developed to solve control problems appearing in the field of Networked
Control Systems (NCS). Several models and methodologies have been proposed to
measure different resources consumptions. The use of bandwidth, computational
load and energy resources have been investigated. This analysis shows how the
parameters of the system impacts on the resources efficiency. Moreover, the
proposed system has been compared with its equivalent discrete-time solution. In
the experiments, an application of NCS for mobile robots navigation has been set
up and its resource usage efficiency has been analysed.
PMID- 29346320
TI - C-Phycocyanin and Phycocyanobilin as Remyelination Therapies for Enhancing
Recovery in Multiple Sclerosis and Ischemic Stroke: A Preclinical Perspective.
AB - Myelin loss has a crucial impact on behavior disabilities associated to Multiple
Sclerosis (MS) and Ischemic Stroke (IS). Although several MS therapies are
approved, none of them promote remyelination in patients, limiting their ability
for chronic recovery. With no available therapeutic options, enhanced
demyelination in stroke survivors is correlated with a poorer behavioral
recovery. Here, we show the experimental findings of our group and others
supporting the remyelinating effects of C-Phycocyanin (C-PC), the main
biliprotein of Spirulina platensis and its linked tetrapyrrole Phycocyanobilin
(PCB), in models of these illnesses. C-PC promoted white matter regeneration in
rats and mice affected by experimental autoimmune encephalomyelitis. Electron
microscopy analysis in cerebral cortex from ischemic rats revealed a potent
remyelinating action of PCB treatment after stroke. Among others biological
processes, we discussed the role of regulatory T cell induction, the control of
oxidative stress and pro-inflammatory mediators, gene expression modulation and
COX-2 inhibition as potential mechanisms involved in the C-PC and PCB effects on
the recruitment, differentiation and maturation of oligodendrocyte precursor
cells in demyelinated lesions. The assembled evidence supports the implementation
of clinical trials to demonstrate the recovery effects of C-PC and PCB in these
diseases.
PMID- 29346322
TI - Regioselective Synthesis of Procyanidin B6, A 4-6-Condensed (+)-Catechin Dimer,
by Intramolecular Condensation.
AB - Proanthocyanidins, also known as condensed tannins or oligomeric flavonoids, are
found in many edible plants and exhibit interesting biological activities.
Herein, we report a new, simple method for the stereoselective synthesis of
procyanidin B6, a (+)-catechin-(4-6)-(+)-catechin dimer, by Lewis acid-catalyzed
intramolecular condensation. The 5-O-t-butyldimethylsilyl (TBDMS) group of
5,7,3'4'-tetra-O-TBDMS-(+)-catechin was regioselectively removed using
trifluoroacetic acid, leading to the "regio-controlled" synthesis of procyanidin
B6. The 5-hydroxyl group of the 7,3',4'-tri-O-TBDMS-(+)-catechin nucleophile and
the 3-hydroxyl group of 5,7,3',4'-tetra-O-benzylated-(+)-catechin electrophile
were connected with an azelaic acid. The subsequent SnCl4-catalyzed
intramolecular condensation proceeded smoothly to give the 4-6-condensed catechin
dimer. This is the first report on the complete regioselective synthesis of a 4-6
connected oligomer without modifying the 8-position.
PMID- 29346323
TI - Sculling Compensation Algorithm for SINS Based on Two-Time Scale Perturbation
Model of Inertial Measurements.
AB - In order to decrease the velocity sculling error under vibration environments, a
new sculling error compensation algorithm for strapdown inertial navigation
system (SINS) using angular rate and specific force measurements as inputs is
proposed in this paper. First, the sculling error formula in incremental velocity
update is analytically derived in terms of the angular rate and specific force.
Next, two-time scale perturbation models of the angular rate and specific force
are constructed. The new sculling correction term is derived and a gravitational
search optimization method is used to determine the parameters in the two-time
scale perturbation models. Finally, the performance of the proposed algorithm is
evaluated in a stochastic real sculling environment, which is different from the
conventional algorithms simulated in a pure sculling circumstance. A series of
test results demonstrate that the new sculling compensation algorithm can achieve
balanced real/pseudo sculling correction performance during velocity update with
the advantage of less computation load compared with conventional algorithms.
PMID- 29346325
TI - Synthesis and Antimicrobial Activity of 4-Substituted 1,2,3-Triazole-Coumarin
Derivatives.
AB - A new series of coumarin-1,2,3-triazole conjugates with varied alkyl, phenyl and
heterocycle moieties at C-4 of the triazole nucleus were synthesized using a
copper(I)-catalysed Huisgen 1,3-dipolar cycloaddition reaction of corresponding O
propargylated coumarin (3) or N-propargylated coumarin (6) with alkyl or aryl
azides. Based on their minimal inhibitory concentrations (MICs) against selected
microorganisms, six out of twenty-six compounds showed significant antibacterial
activity towards Enterococcus faecalis (MIC = 12.5-50 ug/mL). Moreover, the
synthesized triazoles show relatively low toxicity against human erythrocytes.
PMID- 29346326
TI - Lipid Membrane Nanosensors for Environmental Monitoring: The Art, the
Opportunities, and the Challenges.
AB - The advent of nanotechnology has brought along new materials, techniques, and
concepts, readily adaptable to lipid membrane-based biosensing. The transition
from micro-sensors to nano-sensors is neither straightforward nor effortless, yet
it leads to devices with superior analytical characteristics: ultra-low
detectability, small sample volumes, better capabilities for integration, and
more available bioelements and processes. Environmental monitoring remains a
complicated field dealing with a large variety of pollutants, several
decomposition products, or secondary chemicals produced ad hoc in the short- or
medium term, many sub-systems affected variously, and many processes largely
unknown. The new generation of lipid membranes, i.e., nanosensors, has the
potential for developing monitors with site-specific analytical performance and
operational stability, as well as analyte-tailored types of responses. This
review presents the state-of-the art, the opportunities for niche applicability,
and the challenges that lie ahead.
PMID- 29346327
TI - Enhanced Isotopic Ratio Outlier Analysis (IROA) Peak Detection and Identification
with Ultra-High Resolution GC-Orbitrap/MS: Potential Application for
Investigation of Model Organism Metabolomes.
AB - Identifying non-annotated peaks may have a significant impact on the
understanding of biological systems. In silico methodologies have focused on ESI
LC/MS/MS for identifying non-annotated MS peaks. In this study, we employed in
silico methodology to develop an Isotopic Ratio Outlier Analysis (IROA) workflow
using enhanced mass spectrometric data acquired with the ultra-high resolution GC
Orbitrap/MS to determine the identity of non-annotated metabolites. The higher
resolution of the GC-Orbitrap/MS, together with its wide dynamic range, resulted
in more IROA peak pairs detected, and increased reliability of chemical formulae
generation (CFG). IROA uses two different 13C-enriched carbon sources (randomized
95% 12C and 95% 13C) to produce mirror image isotopologue pairs, whose mass
difference reveals the carbon chain length (n), which aids in the identification
of endogenous metabolites. Accurate m/z, n, and derivatization information are
obtained from our GC/MS workflow for unknown metabolite identification, and aids
in silico methodologies for identifying isomeric and non-annotated metabolites.
We were able to mine more mass spectral information using the same Saccharomyces
cerevisiae growth protocol (Qiu et al. Anal. Chem 2016) with the ultra-high
resolution GC-Orbitrap/MS, using 10% ammonia in methane as the CI reagent gas. We
identified 244 IROA peaks pairs, which significantly increased IROA detection
capability compared with our previous report (126 IROA peak pairs using a GC
TOF/MS machine). For 55 selected metabolites identified from matched IROA CI and
EI spectra, using the GC-Orbitrap/MS vs. GC-TOF/MS, the average mass deviation
for GC-Orbitrap/MS was 1.48 ppm, however, the average mass deviation was 32.2 ppm
for the GC-TOF/MS machine. In summary, the higher resolution and wider dynamic
range of the GC-Orbitrap/MS enabled more accurate CFG, and the coupling of
accurate mass GC/MS IROA methodology with in silico fragmentation has great
potential in unknown metabolite identification, with applications for
characterizing model organism networks.
PMID- 29346328
TI - Comparison of SVM, RF and ELM on an Electronic Nose for the Intelligent
Evaluation of Paraffin Samples.
AB - Paraffin odor intensity is an important quality indicator when a paraffin
inspection is performed. Currently, paraffin odor level assessment is mainly
dependent on an artificial sensory evaluation. In this paper, we developed a
paraffin odor analysis system to classify and grade four kinds of paraffin
samples. The original feature set was optimized using Principal Component
Analysis (PCA) and Partial Least Squares (PLS). Support Vector Machine (SVM),
Random Forest (RF), and Extreme Learning Machine (ELM) were applied to three
different feature data sets for classification and level assessment of paraffin.
For classification, the model based on SVM, with an accuracy rate of 100%, was
superior to that based on RF, with an accuracy rate of 98.33-100%, and ELM, with
an accuracy rate of 98.01-100%. For level assessment, the R2 related to the
training set was above 0.97 and the R2 related to the test set was above 0.87.
Through comprehensive comparison, the generalization of the model based on ELM
was superior to those based on SVM and RF. The scoring errors for the three
models were 0.0016-0.3494, lower than the error of 0.5-1.0 measured by industry
standard experts, meaning these methods have a higher prediction accuracy for
scoring paraffin level.
PMID- 29346329
TI - Anti-Phytopathogenic and Cytotoxic Activities of Crude Extracts and Secondary
Metabolites of Marine-Derived Fungi.
AB - Thirty-one isolates belonging to eight genera in seven orders were identified
from 141 strains that were isolated from several marine plants. Alternaria sp.
and Fusarium sp. were found to be the predominant fungi. Evaluation of the anti
phytopathogenic bacterial and fungal activities, as well as the cytotoxicity of
these 31 extracts, revealed that most of them displayed different levels of
bioactivities. Due to their interesting bioactivities, two fungal strains
Fusarium equiseti (P18) and Alternaria sp. (P8)-were selected for chemical
investigation and compounds 1-4 were obtained. The structure of 1 was elucidated
by 1D and 2D NMR analysis, as well as high-resolution electrospray ionization
mass spectroscopy (HRESIMS), and the absolute configuration of its stereogenic
carbon (C-11) was established by comparison of the experimental and calculated
electronic circular-dichroism (ECD) spectra. Moreover, alterperylenol (4)
exhibited antibacterial activity against Clavibacter michiganensis with a minimum
inhibitory concentration (MIC) of 1.95 MUg/mL, which was 2-fold stronger than
that of streptomycin sulfate. Additionally, an antibacterial mechanism study
revealed that 4 caused membrane hyperpolarization without evidence of destruction
of cell membrane integrity. Furthermore, stemphyperylenol (3) displayed potent
antifungal activity against Pestallozzia theae and Alternaria brassicicola with
MIC values equal to those of carbendazim. The cytotoxicity of 1 and 2 against
human lung carcinoma (A-549), human cervical carcinoma (HeLa), and human hepatoma
(HepG2) cell lines were also evaluated.
PMID- 29346330
TI - Formulation of Poloxamers for Drug Delivery.
AB - Poloxamers, also known as Pluronics(r), are block copolymers of poly(ethylene
oxide) (PEO) and poly(propylene oxide) (PPO), which have an amphiphilic character
and useful association and adsorption properties emanating from this. Poloxamers
find use in many applications that require solubilization or stabilization of
compounds and also have notable physiological properties, including low toxicity.
Accordingly, poloxamers serve well as excipients for pharmaceuticals. Current
challenges facing nanomedicine revolve around the transport of typically water
insoluble drugs throughout the body, followed by targeted delivery. Judicious
design of drug delivery systems leads to improved bioavailability, patient
compliance and therapeutic outcomes. The rich phase behavior (micelles,
hydrogels, lyotropic liquid crystals, etc.) of poloxamers makes them amenable to
multiple types of processing and various product forms. In this review, we first
present the general solution behavior of poloxamers, focusing on their self
assembly properties. This is followed by a discussion of how the self-assembly
properties of poloxamers can be leveraged to encapsulate drugs using an array of
processing techniques including direct solubilization, solvent displacement
methods, emulsification and preparation of kinetically-frozen nanoparticles.
Finally, we conclude with a summary and perspective.
PMID- 29346332
TI - Owners and Veterinary Surgeons in the United Kingdom Disagree about What Should
Happen during a Small Animal Vaccination Consultation.
AB - Dog and cat vaccination consultations are a common part of small animal practice
in the United Kingdom. Few data are available describing what happens during
those consultations or what participants think about their content. The aim of
this novel study was to investigate the attitudes of dog and cat owners and
veterinary surgeons towards the content of small animal vaccination
consultations. Telephone interviews with veterinary surgeons and pet owners
captured rich qualitative data. Thematic analysis was performed to identify key
themes. This study reports the theme describing attitudes towards the content of
the consultation. Diverse preferences exist for what should be prioritised during
vaccination consultations, and mismatched expectations may lead to negative
experiences. Vaccination consultations for puppies and kittens were described to
have a relatively standardised structure with an educational and preventative
healthcare focus. In contrast, adult pet vaccination consultations were described
to focus on current physical health problems with only limited discussion of
preventative healthcare topics. This first qualitative exploration of UK
vaccination consultation expectations suggests that the content and consistency
of adult pet vaccination consultations may not meet the needs or expectations of
all participants. Redefining preventative healthcare to include all preventable
conditions may benefit owners, pets and veterinary surgeons, and may help to
provide a clearer structure for adult pet vaccination consultations. This study
represents a significant advance our understanding of this consultation type.
PMID- 29346335
TI - Notes from the Field: Legionellosis Outbreak Associated with a Hotel Aquatics
Facility - Tennessee, 2017.
PMID- 29346331
TI - Growth Hormone (GH) and Cardiovascular System.
AB - This review describes the positive effects of growth hormone (GH) on the
cardiovascular system. We analyze why the vascular endothelium is a real internal
secretion gland, whose inflammation is the first step for developing
atherosclerosis, as well as the mechanisms by which GH acts on vessels improving
oxidative stress imbalance and endothelial dysfunction. We also report how GH
acts on coronary arterial disease and heart failure, and on peripheral arterial
disease, inducing a neovascularization process that finally increases flow in
ischemic tissues. We include some preliminary data from a trial in which GH or
placebo is given to elderly people suffering from critical limb ischemia, showing
some of the benefits of the hormone on plasma markers of inflammation, and the
safety of GH administration during short periods of time, even in diabetic
patients. We also analyze how Klotho is strongly related to GH, inducing, after
being released from the damaged vascular endothelium, the pituitary secretion of
GH, most likely to repair the injury in the ischemic tissues. We also show how GH
can help during wound healing by increasing the blood flow and some neurotrophic
and growth factors. In summary, we postulate that short-term GH administration
could be useful to treat cardiovascular diseases.
PMID- 29346334
TI - Effect of Gastrointestinal Bleeding on Gastrointestinal Stromal Tumor Patients: A
Retrospective Cohort Study.
AB - BACKGROUND The contemporary risk classification criteria of gastrointestinal
stromal tumors (GISTs) may still have room to improve. The aim of our research
was to analyze the impact factors for GIST patients' relapse-free survival (RFS).
Furthermore, we explore whether gastrointestinal (1) bleeding will be a valuable
indicator to predict GIST patients' prognosis. MATERIAL AND METHODS R0 resection
GISTs patients were retrospectively enrolled during an 8-year period at West
China Hospital of Sichuan University, and all patients' data were from the WCHSU
GIST database. Of a total of 333 GIST patients, 164 patients had GI bleeding.
Univariate analysis and Cox regression analysis were used to calculate the
survival and recurrence rates. RESULTS Compared with non-GI-bleeding patients, GI
bleeding patients had a shorter relapse-free survival (RFS, P=0.003), but among
the different risk groups, GI bleeding only affected the RFS rate of the high
risk group. A Cox regression analysis illustrated that tumor site (P<0.001),
tumor size (P=0.009), mitotic index (P<0.001), tumor rupture (P<0.001), and GI
bleeding (P=0.01) were independent indicators for GIST patients' RFS. CONCLUSIONS
Our study demonstrates that the RFS of GIST patients with GI bleeding was
significantly shorter than that of non-GI-bleeding patients, and GI bleeding was
an independent negative factor predicting RFS, while GI bleeding had more
influence among high-risk patients.
PMID- 29346333
TI - Platelet Rich Plasma: New Insights for Cutaneous Wound Healing Management.
AB - The overall increase of chronic degenerative diseases associated with ageing
makes wound care a tremendous socioeconomic burden. Thus, there is a growing need
to develop novel wound healing therapies to improve cutaneous wound healing. The
use of regenerative therapies is becoming increasingly popular due to the low
invasive procedures needed to apply them. Platelet-rich plasma (PRP) is gaining
interest due to its potential to stimulate and accelerate the wound healing
process. The cytokines and growth factors forming PRP play a crucial role in the
healing process. This article reviews the emerging field of skin wound
regenerative therapies with particular emphasis on PRP and the role of growth
factors in the wound healing process.
PMID- 29346336
TI - Respiratory Syncytial Virus Seasonality - United States, 2014-2017.
AB - Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract
infection in young children worldwide (1-3). In the United States, RSV infection
results in >57,000 hospitalizations and 2 million outpatient visits each year
among children aged <5 years (3). Recent studies have highlighted the importance
of RSV in adults as well as children (4). CDC reported RSV seasonality
nationally, by U.S. Department of Health and Human Services (HHS) regions* and
for the state of Florida, using a new statistical method that analyzes polymerase
chain reaction (PCR) laboratory detections reported to the National Respiratory
and Enteric Virus Surveillance System (NREVSS)
(https://www.cdc.gov/surveillance/nrevss/index.html). Nationally, across three
RSV seasons, lasting from the week ending July 5, 2014 through July 1, 2017, the
median RSV onset occurred at week 41 (mid-October), and lasted 31 weeks until
week 18 (early May). The median national peak occurred at week 5 (early
February). Using these new methods, RSV season circulation patterns differed from
those reported from previous seasons (5). Health care providers and public health
officials use RSV circulation data to guide diagnostic testing and to time the
administration of RSV immunoprophylaxis for populations at high risk for severe
respiratory illness (6). With several vaccines and other immunoprophlyaxis
products in development, estimates of RSV circulation are also important to the
design of clinical trials and future vaccine effectiveness studies.
PMID- 29346337
TI - Notes from the Field: Baylisascaris procyonis Encephalomyelitis in a Toddler -
King County, Washington, 2017.
PMID- 29346339
TI - QuickStats: Percentage Distribution* of Adult Day Services Center Participants,
by Place of Residence? - National Study of Long-Term Care Providers, United
States, 2016.
AB - In 2016, 51.5% of adult day services center participants lived in a private
residence with relative(s), 19.9% lived alone in a private residence, 16.3% lived
in an assisted living/residential care community, 5.3% lived in a private
residence with nonrelative(s), 4.5% had another living arrangement, and 1.5%
lived in a nursing home.
PMID- 29346338
TI - Current Cigarette Smoking Among Adults - United States, 2016.
AB - The U.S. Surgeon General has concluded that the burden of death and disease from
tobacco use in the United States is overwhelmingly caused by cigarettes and other
combusted tobacco products (1). Cigarettes are the most commonly used tobacco
product among U.S. adults, and about 480,000 U.S. deaths per year are caused by
cigarette smoking and secondhand smoke exposure (1). To assess progress toward
the Healthy People 2020 target of reducing the proportion of U.S. adults aged
>=18 years who smoke cigarettes to <=12.0% (objective TU-1.1),* CDC analyzed data
from the 2016 National Health Interview Survey (NHIS). In 2016, the prevalence of
current cigarette smoking among adults was 15.5%, which was a significant decline
from 2005 (20.9%); however, no significant change has occurred since 2015
(15.1%). In 2016, the prevalence of cigarette smoking was higher among adults who
were male, aged 25-64 years, American Indian/Alaska Native or multiracial, had a
General Education Development (GED) certificate, lived below the federal poverty
level, lived in the Midwest or South, were uninsured or insured through Medicaid,
had a disability/limitation, were lesbian, gay, or bisexual (LGB), or had serious
psychological distress. During 2005-2016, the percentage of ever smokers who quit
smoking increased from 50.8% to 59.0%. Proven population-based interventions are
critical to reducing the health and economic burden of smoking-related diseases
among U.S. adults, particularly among subpopulations with the highest smoking
prevalences (1,2).
PMID- 29346341
TI - Erratum: Vol. 66, No. 50.
PMID- 29346340
TI - Disparities in Preconception Health Indicators - ?Behavioral Risk Factor
Surveillance System, 2013-2015, and Pregnancy Risk Assessment Monitoring System,
2013-2014.
AB - PROBLEM/CONDITION: Preconception health is a broad term that encompasses the
overall health of nonpregnant women during their reproductive years (defined here
as aged 18-44 years). Improvement of both birth outcomes and the woman's health
occurs when preconception health is optimized. Improving preconception health
before and between pregnancies is critical for reducing maternal and infant
mortality and pregnancy-related complications. The National Preconception Health
and Health Care Initiative's Surveillance and Research work group suggests ten
prioritized indicators that states can use to monitor programs or activities for
improving the preconception health status of women of reproductive age. This
report includes overall and stratified estimates for nine of these preconception
health indicators. REPORTING PERIOD: 2013-2015. DESCRIPTION OF SYSTEMS: Survey
data from two surveillance systems are included in this report. The Behavioral
Risk Factor Surveillance System (BRFSS) is an ongoing state-based, landline and
cellular telephone survey of noninstitutionalized adults in the United States
aged >=18 years that is conducted by state and territorial health departments.
BRFSS is the main source of self-reported data for states on health risk
behaviors, chronic health conditions, and preventive health services primarily
related to chronic disease in the United States. The Pregnancy Risk Assessment
Monitoring System (PRAMS) is an ongoing U.S. state- and population-based
surveillance system administered collaboratively by CDC and state health
departments. PRAMS is designed to monitor selected maternal behaviors,
conditions, and experiences that occur before, during, and shortly after
pregnancy that are self-reported by women who recently delivered a live-born
infant. This report summarizes BRFSS and PRAMS data on nine of 10 prioritized
preconception health indicators (i.e., depression, diabetes, hypertension,
current cigarette smoking, normal weight, recommended physical activity, recent
unwanted pregnancy, prepregnancy multivitamin use, and postpartum use of a most
or moderately effective contraceptive method) for which the most recent data are
available. BRFSS data from all 50 states and the District of Columbia were used
for six preconception health indicators: depression, diabetes (excluded if
occurring only during pregnancy or if limited to borderline/prediabetes
conditions), hypertension (excluded if occurring only during pregnancy or if
limited to borderline/prehypertension conditions), current cigarette smoking,
normal weight, and recommended physical activity. PRAMS data from 30 states, the
District of Columbia, and New York City were used for three preconception health
indicators: recent unwanted pregnancy, prepregnancy multivitamin use, and
postpartum use of a most or moderately effective contraceptive method by women or
their husbands or partners (i.e., male or female sterilization, hormonal implant,
intrauterine device, injectable contraceptive, oral contraceptive, hormonal
patch, or vaginal ring). Heavy alcohol use during the 3 months before pregnancy
also was included in the prioritized set of 10 indicators, but PRAMS data for
each reporting area are not available until 2016 for that indicator. Therefore,
estimates for heavy alcohol use are not included in this report. All BRFSS
preconception health estimates are based on 2014-2015 data except two
(hypertension and recommended physical activity are based on 2013 and 2015 data).
All PRAMS preconception health estimates rely on 2013-2014 data. Prevalence
estimates of indicators are reported for women aged 18-44 years overall, by age
group, race-ethnicity, health insurance status, and reporting area. Chi-square
tests were conducted to assess differences in indicators by age group,
race/ethnicity, and insurance status. RESULTS: During 2013-2015, prevalence
estimates of indicators representing risk factors were generally highest and
prevalence estimates of health-promoting indicators were generally lowest among
older women (35-44 years), non-Hispanic black women, uninsured women, and those
residing in southern states. For example, prevalence of ever having been told by
a health care provider that they had a depressive disorder was highest among
women aged 35-44 years (23.1%) and lowest among women aged 18-24 years (19.2%).
Prevalence of postpartum use of a most or moderately effective method of
contraception was lowest among women aged 35-44 years (50.6%) and highest among
younger women aged 18-24 years (64.9%). Self-reported prepregnancy multivitamin
use and getting recommended levels of physical activity were lowest among non
Hispanic black women (21.6% and 42.8%, respectively) and highest among non
Hispanic white women (37.8% and 53.8%, respectively). Recent unwanted pregnancy
was lowest among non-Hispanic white women and highest among non-Hispanic black
women (5.0% and 11.6%, respectively). All but three indicators (diabetes,
hypertension, and use of a most or moderately effective contraceptive method)
varied by insurance status; for instance, prevalence of current cigarette smoking
was higher among uninsured women (21.0%) compared with insured women (16.1%), and
prevalence of normal weight was lower among women who were uninsured (38.6%),
compared with women who were insured (46.1%). By reporting area, the range of
women reporting ever having been told by a health care provider that they had
diabetes was 5.0% (Alabama) to 1.9% (Utah), and women reporting ever having been
told by a health care provider that they had hypertension ranged from 19.2%
(Mississippi) to 7.0% (Minnesota). INTERPRETATION: Preconception health risk
factors and health-promoting indicators varied by age group, race/ethnicity,
insurance status, and reporting area. These disparities highlight subpopulations
that might benefit most from interventions that improve preconception health.
PUBLIC HEALTH ACTION: Eliminating disparities in preconception health can
potentially reduce disparities in two of the leading causes of death in early and
middle adulthood (i.e., heart disease and diabetes). Public health officials can
use this information to provide a baseline against which to evaluate state
efforts to improve preconception health.
PMID- 29346342
TI - Attention-Deficit/Hyperactivity Disorder Medication Prescription Claims Among
Privately Insured Women Aged 15-44 Years - United States, 2003-2015.
AB - Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder
that affects individuals across the lifespan. ADHD medication use among pregnant
women is increasing (1), but consensus about the safety of ADHD medication use
during pregnancy is lacking. Given that nearly half of U.S. pregnancies are
unintended (2), and early pregnancy is a critical period for fetal development,
examining trends in ADHD medication prescriptions among reproductive-aged women
is important to quantify the population at risk for potential exposure. CDC used
the Truven Health MarketScan Commercial Database* for the period 2003-2015 to
estimate the percentage of women aged 15-44 years with private employer-sponsored
insurance who filled prescriptions for ADHD medications each year. The percentage
of reproductive-aged women who filled at least one ADHD medication prescription
increased 344% from 2003 (0.9% of women) to 2015 (4.0% of women). In 2015, the
most frequently filled medications were mixed amphetamine salts,
lisdexamfetamine, and methylphenidate. Prescribing ADHD medications to
reproductive-aged women is increasingly common; additional research on ADHD
medication safety during pregnancy is warranted to inform women and their health
care providers about any potential risks associated with ADHD medication exposure
before and during pregnancy.
PMID- 29346343
TI - Asthma Mortality Among Persons Aged 15-64 Years, by Industry and Occupation -
United States, 1999-2016.
AB - In 2015, an estimated 18.4 million U.S. adults had current asthma, and 3,396
adult asthma deaths were reported (1). An estimated 11%-21% of asthma deaths
might be attributable to occupational exposures (2). To describe asthma mortality
among persons aged 15-64 years,* CDC analyzed multiple cause-of-death data? for
1999-2016 and industry and occupation information collected from 26 statesS for
the years 1999, 2003, 2004, and 2007-2012. Proportionate mortality ratios (PMRs)
for asthma among persons aged 15-64 years were calculated. During 1999-2016, a
total of 14,296 (42.9%) asthma deaths occurred among males and 19,011 (57.1%)
occurred among females. Based on an estimate that 11%-21% of asthma deaths might
be related to occupational exposures, during this 18-year period, 1,573-3,002
asthma deaths in males and 2,091-3,992 deaths in females might have resulted from
occupational exposures. Some of these deaths might have been averted by
instituting measures to prevent potential workplace exposures. The annual age
adjusted asthma death rate** per 1 million persons aged 15-64 years declined from
13.59 in 1999 to 9.34 in 2016 (p<0.001) among females, and from 9.14 (1999) to
7.78 (2016) (p<0.05) among males. The highest significantly elevated asthma PMRs
for males were for those in the food, beverage, and tobacco products
manufacturing industry (1.82) and for females were for those in the social
assistance industry (1.35) and those in community and social services occupations
(1.46). Elevated asthma mortality among workers in certain industries and
occupations underscores the importance of optimal asthma management and
identification and prevention of potential workplace exposures.
PMID- 29346344
TI - Development of immune and microbial environments is independently regulated in
the mammary gland.
AB - Breastfeeding is important for mammals, providing immunological and
microbiological advantages to neonates, together with the nutritional supply from
the mother. However, the mechanisms of this functional diversity in the mammary
gland remain poorly characterized. Here, we show that, similar to the
gastrointestinal tract, the mammary gland develops immune and microbial
environments consisting of immunoglobulin A (IgA) and the microflora,
respectively, both of which are important for protecting neonates and the mother
from infectious diseases. The IgA production and microflora development are
coordinated in the gastrointestinal tract but seem to be independently regulated
in the mammary gland. In particular, the chemokine (C-C motif) ligand 28 and poly
Ig receptor, crucial molecules for the IgA production in milk, were expressed
normally in germ-free lactating mice but were almost undetectable in postweaning
mothers, regardless of the microflora presence. Our findings offer insights into
potentially improving the quality of breastfeeding, using both immunological and
microbiological approaches.
PMID- 29346346
TI - Protein kinase C-delta (PKCdelta), a marker of inflammation and tuberculosis
disease progression in humans, is important for optimal macrophage killing
effector functions and survival in mice.
AB - This corrects the article DOI: 10.1038/mi.2017.68.
PMID- 29346345
TI - The cytosolic sensor STING is required for intestinal homeostasis and control of
inflammation.
AB - STING (stimulator of interferon genes) is a cytosolic sensor for cyclic
dinucleotides and also an adaptor molecule for intracellular DNA receptors.
Although STING has important functions in the host defense against pathogens and
in autoimmune diseases, its physiological relevance in intestinal homeostasis is
largely unknown. In this study, we show that STING-/- mice presented defective
protective mechanisms of intestinal mucosa, including decreased number of goblet
cells, diminished mucus production, and lower levels of secretory IgA, when
compared with wild-type (WT) mice. Fecal content and microbiota DNA could
activate STING, indicating a role of this molecule in gut. Microbiota composition
was altered in STING-/- mice toward a more inflammatory profile, evidencing a
reduction in the Allobacolum and Bifidobacterium groups along with increase in
Disulfovibrio bacteria. Absence of STING lead to decrease in induced
intraepithelial lymphocytes (IEL) and to increase in group 1 innate lymphoid cell
(ILC1) as well as ILC3 frequencies and decrease in ILC2 in the colon. Development
and function of Foxp3+ and LAP+ regulatory T cells were also compromised in STING
/- mice. Moreover, these mice were highly susceptible to dextran sodium sulfate
induced colitis, T-cell-induced colitis, and enteric Salmonella typhimurium
infection when compared with WT animals. Therefore, our results identify an
important role of STING in maintaining gut homeostasis and also a protective
effect in controlling gut inflammation.
PMID- 29346348
TI - Macrophages regulate lung ILC2 activation via Pla2g5-dependent mechanisms.
AB - Group V phospholipase A2 (Pla2g5) is a lipid-generating enzyme necessary for
macrophage effector functions in pulmonary inflammation. However, the lipid
mediators involved and their cellular targets have not been identified. Mice
lacking Pla2g5 showed markedly reduced lung ILC2 activation and eosinophilia
following repetitive Alternaria Alternata inhalation. While Pla2g5-null mice had
Wt levels of immediate IL-33 release after one Alternaria dose, they failed to
upregulate IL-33 in macrophages following repeated Alternaria administration.
Unexpectedly, while adoptive transfer of bone marrow-derived (BM)-macrophages
restored ILC2 activation and eosinophilia in Alternaria-exposed Pla2g5-null mice,
exogenous IL-33 did not. Conversely, transfers of Pla2g5-null BM-macrophages
reduced inflammation in Alternaria-exposed Wt mice. Mass spectrometry analysis of
free fatty acids (FFAs) demonstrated significantly reduced FFAs (including
linoleic acid (LA) and oleic acid (OA)) in lung and BM-macrophages lacking
Pla2g5. Exogenous administration of LA or LA+OA to Wt mice sharply potentiated IL
33-induced lung eosinophilia and ILC2 expansion in vitro and in vivo. In
contrast, OA potentiated IL-33-induced inflammation and ILC2 expansion in Pla2g5
null mice, but LA was inactive both in vivo and in vitro. Notably, Pla2g5-null
ILC2s showed significantly reduced expression of the FFA-receptor-1 compared to
Wt ILC2s. Thus, macrophage-associated Pla2g5 contributes significantly to type-2
immunity through regulation of IL-33 induction and FFA-driven ILC2 activation.
PMID- 29346347
TI - CD103+CD11b+ mucosal classical dendritic cells initiate long-term switched
antibody responses to flagellin.
AB - Antibody responses induced at mucosal and nonmucosal sites demonstrate a
significant level of autonomy. Here, we demonstrate a key role for mucosal
interferon regulatory factor-4 (IRF4)-dependent CD103+CD11b+ (DP), classical
dendritic cells (cDCs) in the induction of T-dependent immunoglobulin G (IgG) and
immunoglobulin A (IgA) responses in the mesenteric lymph node (MLN) following
systemic immunization with soluble flagellin (sFliC). In contrast, IRF8-dependent
CD103+CD11b- (SP) are not required for these responses. The lack of this response
correlated with a complete absence of sFliC-specific plasma cells in the MLN,
small intestinal lamina propria, and surprisingly also the bone marrow (BM). Many
sFliC-specific plasma cells accumulating in the BM of immunized wild-type mice
expressed alpha4beta7+, suggesting a mucosal origin. Collectively, these results
suggest that mucosal DP cDC contribute to the generation of the sFliC-specific
plasma cell pool in the BM and thus serve as a bridge linking the mucosal and
systemic immune system.
PMID- 29346349
TI - Early treatment of SIV+ macaques with an alpha4beta7 mAb alters virus
distribution and preserves CD4+ T cells in later stages of infection.
AB - Integrin alpha4beta7 mediates the trafficking of leukocytes, including CD4+ T
cells, to lymphoid tissues in the gut. Virus mediated damage to the gut is
implicated in HIV and SIV mediated chronic immune activation and leads to
irreversible damage to the immune system. We employed an immuno-PET/CT imaging
technique to evaluate the impact of an anti-integrin alpha4beta7 mAb alone or in
combination with ART, on the distribution of both SIV infected cells and CD4+
cells in rhesus macaques infected with SIV. We determined that alpha4beta7 mAb
reduced viral antigen in an array of tissues of the lung, spleen, axillary, and
inguinal lymph nodes. These sites are not directly linked to alpha4beta7 mediated
homing; however, the most pronounced reduction in viral load was observed in the
colon. Despite this reduction, alpha4beta7 mAb treatment did not prevent an
apparent depletion of CD4+ T cells in gut in the acute phase of infection that is
characteristic of HIV/SIV infection. However, alpha4beta7 mAb appeared to
facilitate the preservation or restoration of CD4+ T cells in gut tissues at
later stages of infection. Since damage to the gut is believed to play a central
role in HIV pathogenesis, these results support further evaluation of alpha4beta7
antagonists in the study and treatment of HIV disease.
PMID- 29346351
TI - Adolescents and young adults with cancer in New Zealand-understudied and
underserved.
PMID- 29346352
TI - Compassion defined: it's time for doctors to step up.
PMID- 29346350
TI - Epithelial-mesenchymal transition in Crohn's disease.
AB - Crohn's disease (CD) is often accompanied by the complications of intestinal
strictures and fistulas. These complications remain obstacles in CD treatment. In
recent years, the importance of epithelial-mesenchymal transition in the
pathogenesis of CD-associated fistulas and intestinal fibrosis has become
apparent. Epithelial-mesenchymal transition refers to a dynamic change, wherein
epithelial cells lose their polarity and adherence and acquire migratory function
and fibroblast features. During formation of CD-associated fistulas, intestinal
epithelial cells dislocate from the basement membrane and migrate to the lining
of the fistula tracts, where they convert into transitional cells as a
compensatory response under the insufficient wound healing condition. In CD
associated intestinal fibrosis, epithelial-mesenchymal transition may serve as a
source of new fibroblasts and consequently lead to overproduction of
extracellular matrix. In this review, we present current knowledge of epithelial
mesenchymal transition and its role in the pathogenesis of CD in order to
highlight new therapy targets for the associated complications.
PMID- 29346353
TI - The burden of cancer in 25-29 year olds in New Zealand: a case for a wider
adolescent and young adult age range?
AB - AIMS: New Zealand currently defines the adolescent and young adult (AYA) group
for cancer services as young people 12-24 years of age, while other countries
favour a designation of 15-29 years. This study was undertaken to compare cancer
incidence and survival among 25-29 year olds to New Zealand's younger AYA
population and to assess survival for our 15-29 year population against
international benchmarks. METHODS: Diagnostic and demographic information for
cancer registrations between 2000 and 2009 for 25-29 year olds was obtained from
the New Zealand Cancer Registry. Incidence rates (IR) and five-year relative
survival estimates were calculated according to AYA diagnostic group/sub-group,
sex and prioritised ethnicity. RESULTS: 1,541 new primary malignant cancers were
diagnosed (IR: 588 per million). Five-year relative survival was 85%, but was
significantly lower for Maori and Pacific peoples (both 77%) compared to non
Maori/non-Pacific peoples (88%). In the overall 15-29 year AYA cohort, disease
specific outcomes for bone tumours (46%) and breast cancer (64%) were inferior to
international standards. CONCLUSION: New Zealand 25 to 29 year olds are at twice
the risk of developing cancer as those 15-24 years. Given that the survival
disparities identified were remarkably consistent with those for younger AYA,
consideration should be given widening New Zealand's AYA age range.
PMID- 29346354
TI - Compassion from a palliative care perspective.
AB - BACKGROUND: Compassion is a core virtue in medicine and lies at the heart of good
medical care. It connects us to each other and reflects our need for
relationships with others. AIM: Our aim is to explore how palliative care
patients perceive, understand and experience compassion from health
professionals, and to inform clinical practice. METHODS: Seven hospice managers
in the North Island of New Zealand were contacted and invited to join the study.
Twenty participants expressed a desire to participate and were involved in semi
structured face-to-face interviews. A set of questions guided the interviewers
with interviews lasting between 15-60 minutes. RESULTS: In regards to the
question, what is your understanding of compassion?, four central themes emerged:
connection, presence and warmth, respect and caring. When asked, what advice can
you give to trainee health professionals?, participants articulated four themes:
connecting with patients and talking in a way they can understand, treating the
person with respect, showing interest in them and being a positive presence for
them. CONCLUSIONS: Compassion was seen as a connection between the carer and the
patient. Compassion is having a positive presence and warmth; an attitude of
respect and caring. The main advice given by research participants to enhance
compassion is for doctors and nurses to connect, to talk in a way that can be
understood, and show interest and respect to patients facing the end of their
lives.
PMID- 29346355
TI - Increasing rates of people identifying as transgender presenting to Endocrine
Services in the Wellington region.
AB - AIMS: Overseas clinics specialising in management of transgender people have
noted a marked increase in the numbers of people requesting therapy in the last
few years. No data has been presented for New Zealand. We therefore reviewed the
number of transgender people seen in the Wellington Endocrine Service to assess
if the pattern was similar and assess any potential problems for service
delivery. METHODS: Using hospital records, we reviewed the new appointments of
people who were referred for advice on gender reassignment and seen in the
Wellington Endocrine Service from 1990 to 2016. RESULTS: In total, 438 people who
identified as transgender attended the clinic at least once in this period. There
has been a progressive increase in number of people identifying as transgender
presenting to the clinic, particularly since 2010. In addition to increasing
overall numbers, there has been in particular increase in referrals for people
under age 30, as well as an increasing proportion of people requesting female-to
male (FtM) therapy so that it is now approaching the number of people requesting
male-to-female therapy (MtF). CONCLUSION: The pattern observed is comparable to
changes reported overseas. These changes have practical consequences for the
delivery of both secondary and primary level healthcare, requiring an increased
focus on clinical coordination between the relevant medical services and their
links to the primary services sector.
PMID- 29346356
TI - The effect of trampoline parks on presentations to the Christchurch Emergency
Department.
AB - AIMS: To analyse trampoline-related injuries suffered after the opening of two
new trampoline parks in Christchurch. METHODS: Data was collected from three 90
day periods. All trampoline-related injuries were collected from electronic
documentation and coding. Those injured after both arenas opened were contacted
and a semi-structured interview performed. RESULTS: In the 90 days after both
parks opened there were 602 claims for trampoline-related injuries with 106
hospital presentations (55% male). This was a significant increase (p<0.01) from
one year earlier (333 claims, 37 hospital presentations) and the 90 days prior to
their opening (201 claims, 15 hospital presentations). Most injuries affected an
older group of children, aged between 10-14 years (26%, n=28), compared to the
other two periods (p<0.01). There was also a greater proportion of lower-limb
injuries (52%, n=55) compared to the other two periods (p<0.01). Thirty-six
required hospital admission, with 29 operations and an average length of stay of
2.11 days. One trampoline park allowed two or more people to use the same
trampoline at the same time, and had over twice as many presentations (33%, n=35)
than the other trampoline park (14%, n=15). CONCLUSIONS: Christchurch saw a
significant increase in trampoline-related injuries after the opening of two new
parks. These injuries involved an older group of children, affected predominantly
the lower limbs and were more severe than those reported from the use of domestic
trampolines. Consistent with past research, the trampoline park allowing multiple
users had a higher proportion of presentations and more injuries requiring
operative intervention.
PMID- 29346357
TI - Type of cows' milk consumption and relationship to health predictors in New
Zealand preschool children.
AB - AIMS: New Zealand dietary guidelines recommend children from two years of age
consume low- or reduced-fat milk. We aimed to investigate the predictors of type
of milk consumption in preschool children. METHODS: Data were drawn from a cross
sectional study which enrolled preschool children (2-<5 years, n=1,329) from
throughout New Zealand. RESULTS: Cows' milk was consumed regularly by 88% of
children. Of these, 26% consumed plain low- or reduced-fat milk, while 74%
consumed full-fat milk. The adjusted odds of consuming plain low- or reduced-fat
milk were increased in older children: three-year old (OR=1.80, 95% CI 1.29
2.50); four-year old (OR=1.93, 95% CI 1.38-2.72) versus two-year old children,
and were decreased in Maori (OR=0.56, 95% CI 0.36-0.88) and Pacific children
(OR=0.32, 95% CI 0.12-0.86) compared with New Zealand European children.
Approximately 18% of children were overweight/obese. The odds (adjusted for socio
demographic characteristics) of consuming plain low- or reduced-fat milk were
increased in overweight children (OR=1.74, 95% CI 1.20-2.54) than normal weight
children. CONCLUSIONS: The type of milk consumed by preschool children varies
with child demographics and anthropometry. Further research is warranted to
investigate caregivers/parents' knowledge about dietary guidelines and to
determine the causal relationship between obesity and milk type consumption. The
findings of the current study may have important implications for developing and
shaping interventions and in helping shape public health policy and practice to
promote cows' milk consumption in preschool children.
PMID- 29346359
TI - A systematic review of leadership training for medical students.
AB - BACKGROUND: Leadership is increasingly being recognised as an essential
requirement for doctors. Many medical schools are in the process of developing
formal leadership training programmes, but it remains to be elucidated what
characteristics make such programmes effective, and to what extent current
programmes are effective, beyond merely positive learner reactions. This review's
objective was to investigate the effectiveness of undergraduate medical
leadership curricula and to explore common features of effective curricula.
METHODS: A systematic literature search was conducted. Articles describing and
evaluating undergraduate medical leadership curricula were included. Outcomes
were stratified and analysed according to a modified Kirkpatrick's model for
evaluating educational outcomes. RESULTS: Eleven studies met inclusion criteria.
Leadership curricula evaluated were markedly heterogeneous in their duration and
composition. The majority of studies utilised pre- and post- intervention
questionnaires for evaluation. Two studies described randomised controlled trials
with objective measures. Outcomes were broadly positive. Only one study reported
neutral outcomes. CONCLUSIONS: A wide range of leadership curricula have shown
subjective effectiveness, including short interventions. There is limited
objective evidence however, and few studies have measured effectiveness at the
system and patient levels. Further research is needed investigating objective and
downstream outcomes, and use of standard frameworks for evaluation will
facilitate effective comparison of initiatives.
PMID- 29346358
TI - Rates of unsuspected thyroid cancer in multinodular thyroid disease.
AB - BACKGROUND: Previously the risk of concomitant thyroid cancer in multinodular
goitre (MNG) has been reported as approximately 4%. Cancer risk in toxic MNG was
often considered lower than for non-toxic MNG, due to a possible protective
effect of TSH suppression. However, recent American data suggest an approximately
18% risk of occult malignancy in both toxic and non-toxic MNG. AIMS: To assess
malignancy risk in a New Zealand population undergoing thyroidectomy for MNG.
METHODS: Single-centre study of patients undergoing thyroidectomy for MNG from 1
December 2006 to 30 November 2016. RESULTS: Six hundred and two patients
underwent surgery for MNG (448 non-toxic and 154 toxic). Of these, 95/602 (16%)
had thyroid cancer. After excluding patients operated for preoperative suspicion
for cancer, 30/401 (8%) patients with non-toxic MNG and 15/151 (10%) with toxic
MNG had unsuspected or occult thyroid cancer (p=0.358). Patients with toxic MNG
were less likely to undergo preoperative fine needle aspiration than those with
non-toxic MNG (34% vs 52%, respectively p=0.0001). Two-thirds of unsuspected
thyroid cancers were incidental micropapillary carcinomas and unlikely to alter
survival irrespective of therapy. CONCLUSION: Malignancy rates in MNG are higher
than historically reported, although most unsuspected cancers are unlikely to
alter mortality even if diagnosis is delayed.
PMID- 29346360
TI - Evaluation of the Report on Euthanasia for the New Zealand Medical Association by
Grant Gillett.
PMID- 29346361
TI - Publication and authorship challenges experienced by medical students involved in
biomedical research.
PMID- 29346362
TI - Research opportunities for medical students: time flies when you're having fun.
PMID- 29346363
TI - Euthanasia and abortion.
PMID- 29346365
TI - The ISCB Student Council Internship Program: Expanding computational biology
capacity worldwide.
AB - Education and training are two essential ingredients for a successful career. On
one hand, universities provide students a curriculum for specializing in one's
field of study, and on the other, internships complement coursework and provide
invaluable training experience for a fruitful career. Consequently,
undergraduates and graduates are encouraged to undertake an internship during the
course of their degree. The opportunity to explore one's research interests in
the early stages of their education is important for students because it improves
their skill set and gives their career a boost. In the long term, this helps to
close the gap between skills and employability among students across the globe
and balance the research capacity in the field of computational biology. However,
training opportunities are often scarce for computational biology students,
particularly for those who reside in less-privileged regions. Aimed at helping
students develop research and academic skills in computational biology and
alleviating the divide across countries, the Student Council of the International
Society for Computational Biology introduced its Internship Program in 2009. The
Internship Program is committed to providing access to computational biology
training, especially for students from developing regions, and improving
competencies in the field. Here, we present how the Internship Program works and
the impact of the internship opportunities so far, along with the challenges
associated with this program.
PMID- 29346364
TI - Mutations in Caenorhabditis elegans neuroligin-like glit-1, the apoptosis pathway
and the calcium chaperone crt-1 increase dopaminergic neurodegeneration after 6
OHDA treatment.
AB - The loss of dopaminergic neurons is a hallmark of Parkinson's disease, the
aetiology of which is associated with increased levels of oxidative stress. We
used C. elegans to screen for genes that protect dopaminergic neurons against
oxidative stress and isolated glit-1 (gliotactin (Drosophila neuroligin-like)
homologue). Loss of the C. elegans neuroligin-like glit-1 causes increased
dopaminergic neurodegeneration after treatment with 6-hydroxydopamine (6-OHDA),
an oxidative-stress inducing drug that is specifically taken up into dopaminergic
neurons. Furthermore, glit-1 mutants exhibit increased sensitivity to oxidative
stress induced by H2O2 and paraquat. We provide evidence that GLIT-1 acts in the
same genetic pathway as the previously identified tetraspanin TSP-17. After
exposure to 6-OHDA and paraquat, glit-1 and tsp-17 mutants show almost identical,
non-additive hypersensitivity phenotypes and exhibit highly increased induction
of oxidative stress reporters. TSP-17 and GLIT-1 are both expressed in
dopaminergic neurons. In addition, the neuroligin-like GLIT-1 is expressed in
pharynx, intestine and several unidentified cells in the head. GLIT-1 is
homologous, but not orthologous to neuroligins, transmembrane proteins required
for the function of synapses. The Drosophila GLIT-1 homologue Gliotactin in
contrast is required for epithelial junction formation. We report that GLIT-1
likely acts in multiple tissues to protect against 6-OHDA, and that the
epithelial barrier of C. elegans glit-1 mutants does not appear to be
compromised. We further describe that hyperactivation of the SKN-1 oxidative
stress response pathway alleviates 6-OHDA-induced neurodegeneration. In addition,
we find that mutations in the canonical apoptosis pathway and the calcium
chaperone crt-1 cause increased 6-OHDA-induced dopaminergic neuron loss. In
summary, we report that the neuroligin-like GLIT-1, the canonical apoptosis
pathway and the calreticulin CRT-1 are required to prevent 6-OHDA-induced
dopaminergic neurodegeneration.
PMID- 29346366
TI - Testing for soil-transmitted helminth transmission elimination: Analysing the
impact of the sensitivity of different diagnostic tools.
AB - In recent years, an increased focus has been placed upon the possibility of the
elimination of soil-transmitted helminth (STH) transmission using various
interventions including mass drug administration. The primary diagnostic tool
recommended by the WHO is the detection of STH eggs in stool using the Kato-Katz
(KK) method. However, detecting infected individuals using this method becomes
increasingly difficult as the intensity of infection decreases. Newer techniques,
such as qPCR, have been shown to have greater sensitivity than KK, especially at
low prevalence. However, the impact of using qPCR on elimination thresholds is
yet to be investigated. In this paper, we aim to quantify how the sensitivity of
these two diagnostic tools affects the optimal prevalence threshold at which to
declare the interruption of transmission with a defined level of confidence. A
stochastic, individual-based STH transmission model was used in this study to
simulate the transmission dynamics of Ascaris and hookworm. Data from a Kenyan
deworming study were used to parameterize the diagnostic model which was based on
egg detection probabilities. The positive and negative predictive values (PPV and
NPV) were calculated to assess the quality of any given threshold, with the
optimal threshold value taken to be that at which both were maximised. The
threshold prevalence of infection values for declaring elimination of Ascaris
transmission were 6% and 12% for KK and qPCR respectively. For hookworm, these
threshold values are lower at 0.5% and 2% respectively. Diagnostic tests with
greater sensitivity are becoming increasingly important as we approach the
elimination of STH transmission in some regions of the world. For declaring the
elimination of transmission, using qPCR to diagnose STH infection results in the
definition of a higher prevalence, than when KK is used.
PMID- 29346367
TI - Assessment of serum pharmacokinetics and urinary excretion of albendazole and its
metabolites in human volunteers.
AB - BACKGROUND: Soil Transmitted Helminth (STH) infections negatively impact physical
and mental development in human populations. Current WHO guidelines recommend
morbidity control of these infections through mass drug administration (MDA)
using albendazole (ABZ) or mebendazole. Despite major reductions in STH
associated morbidity globally, not all programs have demonstrated the expected
impact on prevalence of parasite infections. These therapeutic failures may be
related to poor programmatic coverage, suboptimal adherence or the exposure of
parasites to sub-therapeutic drug concentrations. As part of the DeWorm3 project,
we sought to characterize the serum disposition kinetics and pattern of urinary
excretion of ABZ and its main metabolites ABZ sulphoxide (ABZSO) and ABZ sulphone
(ABZSO2) in humans, and the assessment of the duration and optimal time point
where ABZ and/or its metabolites can be measured in urine as an indirect
assessment of an individual's adherence to treatment. METHODOLOGY/PRINCIPAL
FINDINGS: Consecutive venous blood and urine samples were collected from eight
(8) human volunteers up to 72 h post-ABZ oral administration. ABZ/metabolites
were quantified by HPLC. The ABZSO metabolite was the main analyte recovered both
in serum and urine. ABZSO Cmax in serum was 1.20 +/- 0.44 MUg/mL, reached at 4.75
h post-treatment. In urine, ABZSO Cmax was 3.24 +/- 1.51 MUg/mL reached at 6.50 h
post-ABZ administration. CONCLUSION/SIGNIFICANCE: Pharmacokinetic data obtained
for ABZ metabolites in serum and urine, including the recovery of the ABZ
sulphoxide derivative up to 72 h in both matrixes and the recovery of the amino
ABZ sulphone metabolite in urine samples, are suggesting the possibility of
developing a urine based method to assess compliance to ABZ treatment. Such an
assay may be useful to optimize ABZ use in human patients. TRIAL REGISTRATION:
ClinicalTrials.gov NCT03192449.
PMID- 29346368
TI - Mechanical feedback coordinates cell wall expansion and assembly in yeast mating
morphogenesis.
AB - The shaping of individual cells requires a tight coordination of cell mechanics
and growth. However, it is unclear how information about the mechanical state of
the wall is relayed to the molecular processes building it, thereby enabling the
coordination of cell wall expansion and assembly during morphogenesis. Combining
theoretical and experimental approaches, we show that a mechanical feedback
coordinating cell wall assembly and expansion is essential to sustain mating
projection growth in budding yeast (Saccharomyces cerevisiae). Our theoretical
results indicate that the mechanical feedback provided by the Cell Wall Integrity
pathway, with cell wall stress sensors Wsc1 and Mid2 increasingly activating
membrane-localized cell wall synthases Fks1/2 upon faster cell wall expansion,
stabilizes mating projection growth without affecting cell shape. Experimental
perturbation of the osmotic pressure and cell wall mechanics, as well as
compromising the mechanical feedback through genetic deletion of the stress
sensors, leads to cellular phenotypes that support the theoretical predictions.
Our results indicate that while the existence of mechanical feedback is essential
to stabilize mating projection growth, the shape and size of the cell are
insensitive to the feedback.
PMID- 29346369
TI - The rise of neglected tropical diseases in the "new Texas".
AB - Within the last five years, the State of Texas has experienced either
transmission or outbreaks of Ebola, chikungunya, West Nile, and Zika virus
infections. Autochthonous transmission of neglected parasitic and bacterial
diseases has also become increasingly reported. The rise of such emerging and
neglected tropical diseases (NTDs) has not occurred by accident but instead
reflects rapidly evolving changes and shifts in a "new" Texas beset by modern and
globalizing forces that include rapid expansions in population together with
urbanization and human migrations, altered transportation patterns, climate
change, steeply declining vaccination rates, and a new paradigm of poverty known
as "blue marble health." Summarized here are the major NTDs now affecting Texas.
In addition to the vector-borne viral diseases highlighted above, there also is a
high level of parasitic infections, including Chagas disease, trichomoniasis, and
possibly leishmaniasis and toxocariasis, as well as typhus-group rickettsiosis, a
vector-borne bacterial infection. I also highlight some of the key shifts in
emerging and neglected disease patterns, partly due to an altered and evolving
economic and ecological landscape in the new Texas, and provide some preliminary
disease burden estimates for the major prevalent and incident NTDs.
PMID- 29346370
TI - Structure, function, and control of the human musculoskeletal network.
AB - The human body is a complex organism, the gross mechanical properties of which
are enabled by an interconnected musculoskeletal network controlled by the
nervous system. The nature of musculoskeletal interconnection facilitates
stability, voluntary movement, and robustness to injury. However, a fundamental
understanding of this network and its control by neural systems has remained
elusive. Here we address this gap in knowledge by utilizing medical databases and
mathematical modeling to reveal the organizational structure, predicted function,
and neural control of the musculoskeletal system. We constructed a highly
simplified whole-body musculoskeletal network in which single muscles connect to
multiple bones via both origin and insertion points. We demonstrated that, using
this simplified model, a muscle's role in this network could offer a theoretical
prediction of the susceptibility of surrounding components to secondary injury.
Finally, we illustrated that sets of muscles cluster into network communities
that mimic the organization of control modules in primary motor cortex. This
novel formalism for describing interactions between the muscular and skeletal
systems serves as a foundation to develop and test therapeutic responses to
injury, inspiring future advances in clinical treatments.
PMID- 29346371
TI - Identification of novel leishmanicidal molecules by virtual and biochemical
screenings targeting Leishmania eukaryotic translation initiation factor 4A.
AB - Leishmaniases are neglected parasitic diseases in spite of the major burden they
inflict on public health. The identification of novel drugs and targets
constitutes a research priority. For that purpose we used Leishmania infantum
initiation factor 4A (LieIF), an essential translation initiation factor that
belongs to the DEAD-box proteins family, as a potential drug target. We modeled
its structure and identified two potential binding sites. A virtual screening of
a diverse chemical library was performed for both sites. The results were
analyzed with an in-house version of the Self-Organizing Maps algorithm combined
with multiple filters, which led to the selection of 305 molecules. Effects of
these molecules on the ATPase activity of LieIF permitted the identification of a
promising hit (208) having a half maximal inhibitory concentration (IC50) of 150
+/- 15 MUM for 1 MUM of protein. Ten chemical analogues of compound 208 were
identified and two additional inhibitors were selected (20 and 48). These
compounds inhibited the mammalian eIF4I with IC50 values within the same range.
All three hits affected the viability of the extra-cellular form of L. infantum
parasites with IC50 values at low micromolar concentrations. These molecules
showed non-significant toxicity toward THP-1 macrophages. Furthermore, their anti
leishmanial activity was validated with experimental assays on L. infantum
intramacrophage amastigotes showing IC50 values lower than 4.2 MUM. Selected
compounds exhibited selectivity indexes between 19 to 38, which reflects their
potential as promising anti-Leishmania molecules.
PMID- 29346372
TI - Ceramides in tracheal aspirates of preterm infants: Marker for bronchopulmonary
dysplasia.
AB - BACKGROUND: In an experimental mouse model we showed that ceramides play a role
in the pathogenesis of bronchopulmonary dysplasia (BPD) and are a potential
target for therapeutic intervention. We investigated whether ceramides are
detectable in tracheal aspirates (TAs) of preterm infants and differ between
infants with or without BPD. METHODS: Infants born <= 32 weeks of gestational age
in need of mechanical ventilation in the first week of life were included. TAs
were obtained directly after intubation and at day 1, 3, 5, 7, and 14. Ceramide
concentrations were measured by tandem mass spectrometry. At 36 weeks
postmenstrual age BPD was defined as having had >= 28 days supplemental oxygen.
RESULTS: 122 infants were included, of which 14 died and 41 developed BPD. All
infants showed an increase in ceramides after the first day of intubation. The
ceramide profile differed significantly between preterm infants who did and did
not develop BPD. However, the ceramide profile had no additional predictive value
for BPD development over GA at birth, birth weight and total days of mechanical
ventilation. CONCLUSIONS: Ceramides are measurable in TAs of preterm born infants
and may be an early marker for BPD development.
PMID- 29346373
TI - Reconciling Pasteur and Darwin to control infectious diseases.
AB - The continual emergence of new pathogens and the increased spread of antibiotic
resistance in bacterial populations remind us that microbes are living entities
that evolve at rates that impact public health interventions. Following the
historical thread of the works of Pasteur and Darwin shows how reconciling
clinical microbiology, ecology, and evolution can be instrumental to
understanding pathology, developing new therapies, and prolonging the efficiency
of existing ones.
PMID- 29346374
TI - Epidemiological investigation into the prevalence of abnormal inter-arm blood
pressure differences among different ethnicities in Xinjiang, China.
AB - OBJECTIVES: The prevalence of and risk factors for IAD among different ethnicity
groups was unknown. Our aim was to investigate the prevalence of and risk factors
for IAD among Han, Uygur and Kazakh ethnicities in Xinjiang. China. METHODS: In
total, 14,618 adult participants (7,799 males and 6,819 females) were recruited
from the Cardiovascular Risk Survey. A 4-stage stratified cluster random sampling
method was used. The participants' personal information and medical history were
assessed by questionnaire. IAD was diagnosed by a noninvasive arteriosclerosis
analyzer. RESULTS: The prevalence of abnormal IAD among the general population
was 14.3%, with 12.5% in the Han, 14.9% in the Uygur, and 16.4% in the Kazakh
populations. The prevalence of abnormal IAD among the hypertensive population was
19.4%, with 17.0% in the Han, 18.1% in the Uygur, and 22.7% in the Kazakh
populations. The prevalence of abnormal IAD increased with age (all P < 0.01) but
was not significantly different between the genders (all P> 0.05). Multivariate
logistic regression analysis showed that age more than 45 years, obesity and
hypertriglyceridemia were significantly associated with a higher prevalence of
IAD. There were different risk factors for abnormal IAD in different ethnicities.
Middle or old age, obesity, ABI and diabetes mellitus were risk factors for the
Han population, smoking was a risk factor in the Uygur population, and obesity
and PAD were risk factors in the Kazakh population. CONCLUSION: The prevalence of
abnormal IAD in the Kazakh participants was higher than that in the Han and Uygur
populations among both the general population and the hypertensive population in
Xinjiang, China. The main risk factors of IAD were age, obesity, and triglyceride
levels. Different ethnicities had different kinds of risk factors for IAD.
PMID- 29346375
TI - How do we reach the girls and women who are the hardest to reach? Inequitable
opportunities in reproductive and maternal health care services in armed conflict
and forced displacement settings in Colombia.
AB - OBJECTIVES: This paper assesses inequalities in access to reproductive and
maternal health services among females affected by forced displacement and sexual
and gender-based violence in conflict settings in Colombia. This was accomplished
through the following approaches: first, we assessed the gaps and gradients in
three selected reproductive and maternal health care services. Second, we
analyzed the patterns of inequalities in reproductive and maternal health care
services and changes over time. And finally, we identified challenges and
strategies for reaching girls and women who are the hardest to reach in conflict
settings, in order to accelerate progress towards universal health coverage and
to contribute to meeting the Sustainable Development Goals of good health and
well-being and gender equality by 2030. METHODS: Three types of data were
required: data about health outcomes (relating to rates of females affected by
conflict), information about reproductive and maternal health care services to
provide a social dimension to unmask inequalities (unmet needs in family
planning, antenatal care and skilled births attendance); and data on the female
population. Data sources used include the National Information System for Social
Protection, the National Registry of Victims, the National Administrative
Department of Statistics, and Demographic Health Survey at three specific time
points: 2005, 2010 and 2015. We estimated the slope index of inequality to
express absolute inequality (gaps) and the concentration index to expresses
relative inequality (gradients), and to understand whether inequality was
eliminated over time. RESULTS: Our findings show that even though absolute health
care service-related inequalities dropped over time, relative inequalities
worsened or remain unchanged. All summary measures still indicated the existence
of inequalities as well as common patterns. Our findings suggest that there is a
pattern of marginal exclusion and incremental patterns of inequality in the
reproductive and maternal health care service provided to female affected by
armed conflict. CONCLUSIONS: Overall, the effects of conflict continue to
threaten reproductive and maternal health in Colombia, impeding progress towards
the realization of universal health care (UHC) and reinforcing already-existing
inequities. Key messages and steps forward include the need to understand the two
distinct patterns of inequalities identified in this study in order to prompt
improved general policy responses. Addressing unmet needs in reproductive and
maternal health requires supporting gender equality and prioritizing the girls
and women in regions with the highest rates of victims of armed conflict, with
the objective of leaving no girl or woman behind. This analysis represents the
first attempt to analyze coverage-related inequality in reproductive and maternal
health care services for female affected by armed conflict in Colombia. As the
World Health Organization and global health systems leaders call for more
inclusive engagement, this approach may serve as the key to shaping people
centred health systems. In this particular case, health care facilities must be
located in close proximity to girls and women in conflict and post-conflict
settings in order to deliver essential reproductive and maternal health care
services. Finally, reducing inequalities in opportunities would not only promote
equity, but also drive sustainable development.
PMID- 29346376
TI - Evaluating the sustainability, scalability, and replicability of an STH
transmission interruption intervention: The DeWorm3 implementation science
protocol.
AB - Hybrid trials that include both clinical and implementation science outcomes are
increasingly relevant for public health researchers that aim to rapidly translate
study findings into evidence-based practice. The DeWorm3 Project is a series of
hybrid trials testing the feasibility of interrupting the transmission of soil
transmitted helminths (STH), while conducting implementation science research
that contextualizes clinical research findings and provides guidance on
opportunities to optimize delivery of STH interventions. The purpose of DeWorm3
implementation science studies is to ensure rapid and efficient translation of
evidence into practice. DeWorm3 will use stakeholder mapping to identify
individuals who influence or are influenced by school-based or community-wide
mass drug administration (MDA) for STH and to evaluate network dynamics that may
affect study outcomes and future policy development. Individual interviews and
focus groups will generate the qualitative data needed to identify factors that
shape, contextualize, and explain DeWorm3 trial outputs and outcomes. Structural
readiness surveys will be used to evaluate the factors that drive health system
readiness to implement novel interventions, such as community-wide MDA for STH,
in order to target change management activities and identify opportunities for
sustaining or scaling the intervention. Process mapping will be used to
understand what aspects of the intervention are adaptable across heterogeneous
implementation settings and to identify contextually-relevant modifiable
bottlenecks that may be addressed to improve the intervention delivery process
and to achieve intervention outputs. Lastly, intervention costs and incremental
cost-effectiveness will be evaluated to compare the efficiency of community-wide
MDA to standard-of-care targeted MDA both over the duration of the trial and over
a longer elimination time horizon.
PMID- 29346377
TI - Assessing the feasibility of interrupting the transmission of soil-transmitted
helminths through mass drug administration: The DeWorm3 cluster randomized trial
protocol.
AB - : Current control strategies for soil-transmitted helminths (STH) emphasize
morbidity control through mass drug administration (MDA) targeting preschool- and
school-age children, women of childbearing age and adults in certain high-risk
occupations such as agricultural laborers or miners. This strategy is effective
at reducing morbidity in those treated but, without massive economic development,
it is unlikely it will interrupt transmission. MDA will therefore need to
continue indefinitely to maintain benefit. Mathematical models suggest that
transmission interruption may be achievable through MDA alone, provided that all
age groups are targeted with high coverage. The DeWorm3 Project will test the
feasibility of interrupting STH transmission using biannual MDA targeting all age
groups. Study sites (population >=80,000) have been identified in Benin, Malawi
and India. Each site will be divided into 40 clusters, to be randomized 1:1 to
three years of twice-annual community-wide MDA or standard-of-care MDA, typically
annual school-based deworming. Community-wide MDA will be delivered door-to-door,
while standard-of-care MDA will be delivered according to national guidelines.
The primary outcome is transmission interruption of the STH species present at
each site, defined as weighted cluster-level prevalence <=2% by quantitative
polymerase chain reaction (qPCR), 24 months after the final round of MDA.
Secondary outcomes include the endline prevalence of STH, overall and by species,
and the endline prevalence of STH among children under five as an indicator of
incident infections. Secondary analyses will identify cluster-level factors
associated with transmission interruption. Prevalence will be assessed using qPCR
of stool samples collected from a random sample of cluster residents at baseline,
six months after the final round of MDA and 24 months post-MDA. A smaller number
of individuals in each cluster will be followed with annual sampling to monitor
trends in prevalence and reinfection throughout the trial. TRIAL REGISTRATION:
ClinicalTrials.gov NCT03014167.
PMID- 29346378
TI - Evaluating the impact of a 'virtual clinic' on patient experience, personal and
provider costs of care in urinary incontinence: A randomised controlled trial.
AB - OBJECTIVE: To evaluate the impact of using a 'virtual clinic' on patient
experience and cost in the care of women with urinary incontinence. MATERIALS AND
METHODS: Women, aged > 18 years referred to a urogynaecology unit were randomised
to either (1) A Standard Clinic or (2) A Virtual Clinic. Both groups completed a
validated, web-based interactive, patient-reported outome measure (ePAQ-Pelvic
Floor), in advance of their appointment followed by either a telephone
consultation (Virtual Clinic) or face-to-face consultation (Standard Care). The
primary outcome was the mean 'short-term outcome scale' score on the Patient
Experience Questionnaire (PEQ). Secondary Outcome Measures included the other
domains of the PEQ (Communications, Emotions and Barriers), Client Satisfaction
Questionnaire (CSQ), Short-Form 12 (SF-12), personal, societal and NHS costs.
RESULTS: 195 women were randomised: 98 received the intervention and 97 received
standard care. The primary outcome showed a non-significant difference between
the two study arms. No significant differences were also observed on the CSQ and
SF-12. However, the intervention group showed significantly higher PEQ domain
scores for Communications, Emotions and Barriers (including following adjustment
for age and parity). Whilst standard care was overall more cost-effective, this
was minimal (L38.04). The virtual clinic also significantly reduced consultation
time (10.94 minutes, compared with a mean duration of 25.9 minutes respectively)
and consultation costs compared to usual care (L31.75 versus L72.17
respectively), thus presenting potential cost-savings in out-patient management.
CONCLUSIONS: The virtual clinical had no impact on the short-term dimension of
the PEQ and overall was not as cost-effective as standard care, due to greater
clinic re-attendances in this group. In the virtual clinic group, consultation
times were briefer, communication experience was enhanced and personal costs
lower. For medical conditions of a sensitive or intimate nature, a virtual clinic
has potential to support patients to communicate with health professionals about
their condition.
PMID- 29346380
TI - Rapidly progressive dementia: An eight year (2008-2016) retrospective study.
AB - BACKGROUND AND PURPOSE: Rapidly progressive dementia (RPD) is an emergency in
cognitive neurology, defined as cognitive impairment affecting the daily living
activities developed over less than 1 year. This study investigated the profile
of patients with rapidly progressive dementia at first presentation. METHODS:
Retrospective case analysis was done in 187 patients with rapidly progressive
dementia who presented to the Postgraduate Institute of Medical Education and
Research, Chandigarh, India from January 2008 to August 2016. Patients were
divided into three groups: (1) Reversible (treatable) secondary dementia group,
(2) Prion dementia group (sporadic Creutzfeldt-Jakob disease), (3) Non-prion
Neurodegenerative and vascular dementias (primary neurodegenerative and vascular
dementia). Cases presenting with delirium secondary to metabolic, drug induced or
septic causes and those with signs of meningitis were excluded. RESULTS:
Secondary reversible causes formed the most common cause for RPD with immune
mediated encephalitides, neoplastic and infectious disorders as the leading
causes. The patients in this series had an younger onset of RPD. Infections
presenting with RPD accounted for the most common cause in our series (39%) with
SSPE (41%) as the leading cause followed by neurosyphilis (17.9%) and progressive
multifocal leukoencephalopathy (15.3%). Immune mediated dementias formed the
second most common (18.1%) etiologic cause for RPD. The neurodegenerative
dementias were third common cause for RPD in our series. Neoplastic disorders and
immune mediated presented early (< 6 months) while neurodegenerative disorders
presented later (> 6 months). CONCLUSIONS: Rapidly progressive dementia is an
emergency in cognitive neurology with potentially treatable or reversible causes
that should be sought for diligently.
PMID- 29346379
TI - A putative lateral flagella of the cystic fibrosis pathogen Burkholderia dolosa
regulates swimming motility and host cytokine production.
AB - Burkholderia dolosa caused an outbreak in the cystic fibrosis clinic at Boston
Children's Hospital and was associated with high mortality in these patients.
This species is part of a larger complex of opportunistic pathogens known as the
Burkholderia cepacia complex (Bcc). Compared to other species in the Bcc, B.
dolosa is highly transmissible; thus understanding its virulence mechanisms is
important for preventing future outbreaks. The genome of one of the outbreak
strains, AU0158, revealed a homolog of the lafA gene encoding a putative lateral
flagellin, which, in other non-Bcc species, is used for movement on solid
surfaces, attachment to host cells, or movement inside host cells. Here, we
analyzed the conservation of the lafA gene and protein sequences, which are
distinct from those of the polar flagella, and found lafA homologs to be present
in numerous beta-proteobacteria but notably absent from most other Bcc species. A
lafA deletion mutant in B. dolosa showed a greater swimming motility than wild
type due to an increase in the number of polar flagella, but did not appear to
contribute to biofilm formation, host cell invasion, or murine lung colonization
or persistence over time. However, the lafA gene was important for cytokine
production in human peripheral blood mononuclear cells, suggesting it may have a
role in recognition by the human immune response.
PMID- 29346381
TI - Control of recollection by slow gamma dominating mid-frequency gamma in
hippocampus CA1.
AB - Behavior is used to assess memory and cognitive deficits in animals like Fmr1
null mice that model Fragile X Syndrome, but behavior is a proxy for unknown
neural events that define cognitive variables like recollection. We identified an
electrophysiological signature of recollection in mouse dorsal Cornu Ammonis 1
(CA1) hippocampus. During a shocked-place avoidance task, slow gamma (SG) (30-50
Hz) dominates mid-frequency gamma (MG) (70-90 Hz) oscillations 2-3 s before
successful avoidance, but not failures. Wild-type (WT) but not Fmr1-null mice
rapidly adapt to relocating the shock; concurrently, SG/MG maxima (SGdom)
decrease in WT but not in cognitively inflexible Fmr1-null mice. During SGdom,
putative pyramidal cell ensembles represent distant locations; during place
avoidance, these are avoided places. During shock relocation, WT ensembles
represent distant locations near the currently correct shock zone, but Fmr1-null
ensembles represent the formerly correct zone. These findings indicate that
recollection occurs when CA1 SG dominates MG and that accurate recollection of
inappropriate memories explains Fmr1-null cognitive inflexibility.
PMID- 29346382
TI - 6-OHDA-induced dopaminergic neurodegeneration in Caenorhabditis elegans is
promoted by the engulfment pathway and inhibited by the transthyretin-related
protein TTR-33.
AB - Oxidative stress is linked to many pathological conditions including the loss of
dopaminergic neurons in Parkinson's disease. The vast majority of disease cases
appear to be caused by a combination of genetic mutations and environmental
factors. We screened for genes protecting Caenorhabditis elegans dopaminergic
neurons from oxidative stress induced by the neurotoxin 6-hydroxydopamine (6
OHDA) and identified the transthyretin-related gene ttr-33. The only described C.
elegans transthyretin-related protein to date, TTR-52, has been shown to mediate
corpse engulfment as well as axon repair. We demonstrate that TTR-52 and TTR-33
have distinct roles. TTR-33 is likely produced in the posterior arcade cells in
the head of C. elegans larvae and is predicted to be a secreted protein. TTR-33
protects C. elegans from oxidative stress induced by paraquat or H2O2 at an
organismal level. The increased oxidative stress sensitivity of ttr-33 mutants is
alleviated by mutations affecting the KGB-1 MAPK kinase pathway, whereas it is
enhanced by mutation of the JNK-1 MAPK kinase. Finally, we provide genetic
evidence that the C. elegans cell corpse engulfment pathway is required for the
degeneration of dopaminergic neurons after exposure to 6-OHDA. In summary, we
describe a new neuroprotective mechanism and demonstrate that TTR-33 normally
functions to protect dopaminergic neurons from oxidative stress-induced
degeneration, potentially by acting as a secreted sensor or scavenger of
oxidative stress.
PMID- 29346383
TI - Seasonally timed treatment programs for Ascaris lumbricoides to increase impact
An investigation using mathematical models.
AB - There is clear empirical evidence that environmental conditions can influence
Ascaris spp. free-living stage development and host reinfection, but the impact
of these differences on human infections, and interventions to control them, is
variable. A new model framework reflecting four key stages of the A. lumbricoides
life cycle, incorporating the effects of rainfall and temperature, is used to
describe the level of infection in the human population alongside the
environmental egg dynamics. Using data from South Korea and Nigeria, we conclude
that settings with extreme fluctuations in rainfall or temperature could exhibit
strong seasonal transmission patterns that may be partially masked by the
longevity of A. lumbricoides infections in hosts; we go on to demonstrate how
seasonally timed mass drug administration (MDA) could impact the outcomes of
control strategies. For the South Korean setting the results predict a
comparative decrease of 74.5% in mean worm days (the number of days the average
individual spend infected with worms across a 12 month period) between the best
and worst MDA timings after four years of annual treatment. The model found no
significant seasonal effect on MDA in the Nigerian setting due to a narrower
annual temperature range and no rainfall dependence. Our results suggest that
seasonal variation in egg survival and maturation could be exploited to maximise
the impact of MDA in certain settings.
PMID- 29346384
TI - Histoplasmosis in Africa: An emerging or a neglected disease?
AB - Histoplasmosis in Africa has markedly increased since the advent of the HIV/AIDS
epidemic but is under-recognised. Pulmonary histoplasmosis may be misdiagnosed as
tuberculosis (TB). In the last six decades (1952-2017), 470 cases of
histoplasmosis have been reported. HIV-infected patients accounted for 38% (178)
of the cases. West Africa had the highest number of recorded cases with 179; the
majority (162 cases) were caused by Histoplasma capsulatum var. dubuosii (Hcd).
From the Southern African region, 150 cases have been reported, and the majority
(119) were caused by H. capsulatum var. capsulatum (Hcc). There have been 12
histoplasmin skin test surveys with rates of 0% to 35% positivity. Most cases of
Hcd presented as localised lesions in immunocompetent persons; however, it was
disseminated in AIDS patients. Rapid diagnosis of histoplasmosis in Africa is
only currently possible using microscopy; antigen testing and PCR are not
available in most of Africa. Treatment requires amphotericin B and itraconazole,
both of which are not licensed or available in several parts of Africa.
PMID- 29346385
TI - Combined effectiveness of anthelmintic chemotherapy and WASH among HIV-infected
adults.
AB - INTRODUCTION: Current global helminth control guidelines focus on regular
deworming of targeted populations for morbidity control. However, water,
sanitation, and hygiene (WASH) interventions may also be important for reducing
helminth transmission. We evaluated the impact of different potential helminth
protective packages on infection prevalence, including repeated treatment with
albendazole and praziquantel with and without WASH access. METHODOLOGY/PRINCIPAL
FINDINGS: We conducted a cohort study nested within a randomized trial of empiric
deworming of HIV-infected adults in Kenya. Helminth infections and infection
intensity were diagnosed using semi-quantitative real-time PCR. We conducted a
manual forward stepwise model building approach to identify if there are packages
of interventions that may be protective against an STH infection of any species
(combined outcome) and each helminth species individually. We conducted secondary
analyses using the same approach only amongst individuals with no anthelmintis
exposure. We used interaction terms to test for potential intervention synergy.
Approximately 22% of the 701 stool samples provided were helminth-infected, most
of which were of low to moderate intensity. The odds of infection with any STH
species were lower for individuals who were treated with albendazole (aOR:0.11,
95%CI: 0.05, 0.20, p<0.001), adjusting for age and sex. Although most WASH
conditions demonstrated minimal additional benefit in reducing the probability of
infection with any STH species, access to safe flooring did appear to offer some
additional protection (aOR:0.34, 95%CI: 0.20, 0.56, p<0.001). For
schistosomiasis, only treatment with praziquantel was protective (aOR:0.30 95%CI:
0.14, 0.60, p = 0.001). Amongst individuals who were not treated with albendazole
or praziquantel, the most protective intervention package to reduce probability
of STH infections included safe flooring (aOR:0.34, 95%CI: 0.20, 0.59, p<0.001)
and latrine access (aOR:0.59, 95%CI: 0.35, 0.99, p = 0.05). Across all species,
there was no evidence of synergy or antagonism between anthelmintic chemotherapy
with albendazole or praziquantel and WASH resources. CONCLUSIONS/SIGNIFICANCE:
Deworming is effective in reducing the probability of helminth infections amongst
HIV-infected adults. With the exception of safe flooring, WASH offers minimal
additional benefit. However, WASH does appear to significantly reduce infection
prevalence in adults who are not treated with chemotherapy. TRIAL REGISTRATION:
ClinicalTrials.gov, NCT00507221.
PMID- 29346386
TI - Histological subtypes of mouse mammary tumors reveal conserved relationships to
human cancers.
AB - Human breast cancer has been characterized by extensive transcriptional
heterogeneity, with dominant patterns reflected in the intrinsic subtypes. Mouse
models of breast cancer also have heterogeneous transcriptomes and we noted that
specific histological subtypes were associated with particular subsets. We
hypothesized that unique sets of genes define each tumor histological type across
mouse models of breast cancer. Using mouse models that contained both gene
expression data and expert pathologist classification of tumor histology on a
sample by sample basis, we predicted and validated gene expression signatures for
Papillary, EMT, Microacinar and other histological subtypes. These signatures
predict known histological events across murine breast cancer models and identify
counterparts of mouse mammary tumor types in subtypes of human breast cancer.
Importantly, the EMT, Adenomyoepithelial, and Solid signatures were predictive of
clinical events in human breast cancer. In addition, a pan-cancer comparison
revealed that the histological signatures were active in a variety of human
cancers such as lung, oral, and esophageal squamous tumors. Finally, the
differentiation status and transcriptional activity implicit within these
signatures was identified. These data reveal that within tumor histology groups
are unique gene expression profiles of differentiation and pathway activity that
stretch well beyond the transgenic initiating events and that have clear
applicability to human cancers. As a result, our work provides a predictive
resource and insights into possible mechanisms that govern tumor heterogeneity.
PMID- 29346387
TI - Inferring the risk factors behind the geographical spread and transmission of
Zika in the Americas.
AB - BACKGROUND: An unprecedented Zika virus epidemic occurred in the Americas during
2015-2016. The size of the epidemic in conjunction with newly recognized health
risks associated with the virus attracted significant attention across the
research community. Our study complements several recent studies which have
mapped epidemiological elements of Zika, by introducing a newly proposed
methodology to simultaneously estimate the contribution of various risk factors
for geographic spread resulting in local transmission and to compute the risk of
spread (or re-introductions) between each pair of regions. The focus of our
analysis is on the Americas, where the set of regions includes all countries,
overseas territories, and the states of the US. METHODOLOGY/PRINCIPAL FINDINGS:
We present a novel application of the Generalized Inverse Infection Model (GIIM).
The GIIM model uses real observations from the outbreak and seeks to estimate the
risk factors driving transmission. The observations are derived from the dates of
reported local transmission of Zika virus in each region, the network structure
is defined by the passenger air travel movements between all pairs of regions,
and the risk factors considered include regional socioeconomic factors, vector
habitat suitability, travel volumes, and epidemiological data. The GIIM relies on
a multi-agent based optimization method to estimate the parameters, and utilizes
a data driven stochastic-dynamic epidemic model for evaluation. As expected, we
found that mosquito abundance, incidence rate at the origin region, and human
population density are risk factors for Zika virus transmission and spread.
Surprisingly, air passenger volume was less impactful, and the most significant
factor was (a negative relationship with) the regional gross domestic product
(GDP) per capita. CONCLUSIONS/SIGNIFICANCE: Our model generates country level
exportation and importation risk profiles over the course of the epidemic and
provides quantitative estimates for the likelihood of introduced Zika virus
resulting in local transmission, between all origin-destination travel pairs in
the Americas. Our findings indicate that local vector control, rather than travel
restrictions, will be more effective at reducing the risks of Zika virus
transmission and establishment. Moreover, the inverse relationship between Zika
virus transmission and GDP suggests that Zika cases are more likely to occur in
regions where people cannot afford to protect themselves from mosquitoes. The
modeling framework is not specific for Zika virus, and could easily be employed
for other vector-borne pathogens with sufficient epidemiological and
entomological data.
PMID- 29346389
TI - Rising up: Fertility trends in Egypt before and after the revolution.
AB - In 2014, Egypt's Demographic and Health Survey (EDHS) documented an increase in
the total fertility rate (TFR) to 3.5, up from a low of 3.0 recorded by the 2008
EDHS. The increase has been anecdotally attributed to the social upheaval
following Egypt's January 2011 revolution, but little is known about when
fertility first began to increase and among which sub-groups of women. Using
birth histories from seven rounds of EDHS (1992-2014), this study reconstructed
fertility rates for single years from 1990-2013 and examined patterns of
childbearing in five-year birth cohorts of women. We found that the decline in
fertility reversed in 2007, earlier than postulated, plateaued and then increased
again in 2013. The increase in TFR coincided with a convergence of fertility
rates across education levels, and there is evidence of a shift toward
childbearing at younger ages among more educated women, which may be inflating
period measures of fertility.
PMID- 29346388
TI - Safety and pharmacokinetic profile of fixed-dose ivermectin with an innovative
18mg tablet in healthy adult volunteers.
AB - : Ivermectin is a pivotal drug for the control of onchocerciasis and lymphatic
filariasis, which is increasingly identified as a useful drug for the control of
other Neglected Tropical Diseases. Its role in the treatment of soil transmitted
helminthiasis through improved efficacy against Trichuris trichiura in
combination with other anthelmintics might accelerate the progress towards
breaking transmission. Ivermectin is a derivative of Avermectin B1, and consists
of an 80:20 mixture of the equipotent homologous 22,23 dehydro B1a and B1b.
Pharmacokinetic characteristics and safety profile of ivermectin allow to explore
innovative uses to further expand its utilization through mass drug
administration campaigns to improve coverage rates. We conducted a phase I
clinical trial with 54 healthy adult volunteers who sequentially received 2
experimental treatments using a new 18 mg ivermectin tablet in a fixed-dose
strategy of 18 and 36 mg single dose regimens, compared to the standard, weight
based 150-200 MUg/kg, regimen. Volunteers were recruited in 3 groups based on
body weight. Plasma concentrations of ivermectin were measured through HPLC up to
168 hours post treatment. Safety data showed no significant differences between
groups and no serious adverse events: headache was the most frequent adverse
event in all treatment groups, none of them severe. Pharmacokinetic parameters
showed a half-life between 81 and 91 h in the different treatment groups. When
comparing the systemic bioavailability (AUC0t and Cmax) of the reference product
(WA-ref) with the other two study groups using fixed doses, we observed an
overall increase in AUC0t and Cmax for the two experimental treatments of 18 mg
and 36 mg. Body mass index (BMI) and weight were associated with t1/2 and V/F,
probably reflecting the high liposolubility of IVM with longer retention times
proportional to the presence of more adipose tissue. Systemic exposure to
ivermectin (AUC0t or Cmax) was not associated with BMI or weight in our study.
These findings contribute to further understand the pharmacokinetic
characteristics of ivermectin, highlighting its safety across different dosing
regimens. They also correlate with known pharmacokinetic parameters showing
stable levels of AUC and Cmax across a wide range of body weights, which
justifies the strategy of fix dosing from a pharmacokinetic perspective. TRIAL
REGISTRATION: ClinicalTrials.gov NCT03173742.
PMID- 29346390
TI - Africanized bees extend their distribution in California.
AB - Africanized honey bees (Apis mellifera) arrived in the western hemisphere in the
1950s and quickly spread north reaching California in the 1990s. These bees are
highly defensive and somewhat more difficult to manage for commercial purposes
than the European honey bees traditionally kept. The arrival of these bees and
their potentially replacing European bees over much of the state is thus of great
concern. After a 25 year period of little systematic sampling, a recent small
scale study found Africanized honey bees in the Bay Area of California, far north
of their last recorded distribution. The purpose of the present study was to
expand this study by conducting more intensive sampling of bees from across
northern California. We found Africanized honey bees as far north as Napa and
Sacramento. We also found Africanized bees in all counties south of these
counties. Africanized honey bees were particularly abundant in parts of the
central valley and Monterey. This work suggests the northern spread of
Africanized honey bees may not have stopped. They may still be moving north at a
slow rate, although due to the long gaps in sampling it is currently impossible
to tell for certain. Future work should routinely monitor the distribution of
these bees to distinguish between these two possibilities.
PMID- 29346392
TI - Sequential linear regression with online standardized data.
AB - The present study addresses the problem of sequential least square
multidimensional linear regression, particularly in the case of a data stream,
using a stochastic approximation process. To avoid the phenomenon of numerical
explosion which can be encountered and to reduce the computing time in order to
take into account a maximum of arriving data, we propose using a process with
online standardized data instead of raw data and the use of several observations
per step or all observations until the current step. Herein, we define and study
the almost sure convergence of three processes with online standardized data: a
classical process with a variable step-size and use of a varying number of
observations per step, an averaged process with a constant step-size and use of a
varying number of observations per step, and a process with a variable or
constant step-size and use of all observations until the current step. Their
convergence is obtained under more general assumptions than classical ones. These
processes are compared to classical processes on 11 datasets for a fixed total
number of observations used and thereafter for a fixed processing time. Analyses
indicate that the third-defined process typically yields the best results.
PMID- 29346391
TI - Development and validation of a population based risk algorithm for obesity: The
Obesity Population Risk Tool (OPoRT).
AB - BACKGROUND: Given the dramatic rise in the prevalence of obesity, greater focus
on prevention is necessary. We sought to develop and validate a population risk
tool for obesity to inform prevention efforts. METHODS: We developed the Obesity
Population Risk Tool (OPoRT) using the longitudinal National Population Health
Survey and sex-specific Generalized Estimating Equations to predict the 10-year
risk of obesity among adults 18 and older. The model was validated using a
bootstrap approach accounting for the survey design. Model performance was
measured by the Brier statistic, discrimination was measured by the C-statistic,
and calibration was assessed using the Hosmer-Lemeshow Goodness of Fit Chi Square
(HL chi2). RESULTS: Predictive factors included baseline body mass index, age,
time and their interactions, smoking status, living arrangements, education,
alcohol consumption, physical activity, and ethnicity. OPoRT showed good
performance for males and females (Brier 0.118 and 0.095, respectively),
excellent discrimination (C statistic >= 0.89) and achieved calibration (HL chi2
<20). CONCLUSION: OPoRT is a valid and reliable algorithm that can be applied to
routinely collected survey data to estimate the risk of obesity and identify
groups at increased risk of obesity. These results can guide prevention efforts
aimed at reducing the population burden of obesity.
PMID- 29346393
TI - Computational study of HIV gp120 as a target for polyanionic entry inhibitors:
Exploiting the V3 loop region.
AB - Multiple approaches are being utilized to develop therapeutics to treat HIV
infection. One approach is designed to inhibit entry of HIV into host cells, with
a target being the viral envelope glycoprotein, gp120. Polyanionic compounds have
been shown to be effective in inhibiting HIV entry, with a mechanism involving
electrostatic interactions with the V3 loop of gp120 being proposed. In this
study, we applied computational methods to elucidate molecular interactions
between the repeat unit of the precisely alternating polyanion, Poly(4,4'
stilbenedicarboxylate-alt-maleic acid) (DCSti-alt-MA) and the V3 loop of gp120
from strains of HIV against which these polyanions were previously tested (IIIb,
BaL, 92UG037, JR-CSF) as well as two strains for which gp120 crystal structures
are available (YU2, 2B4C). Homology modeling was used to create models of the
gp120 proteins. Using monomers of the gp120 protein, we applied extensive
molecular dynamics simulations to obtain dominant morphologies that represent a
variety of open-closed states of the V3 loop to examine the interaction of 112
ligands of the repeating units of DCSti-alt-MA docked to the V3 loop and
surrounding residues. Using the distance between the V1/V2 and V3 loops of gp120
as a metric, we revealed through MD simulations that gp120 from the lab-adapted
strains (BaL and IIIb), which are more susceptible to inhibition by DCSti-alt-MA,
clearly transitioned to the closed state in one replicate of each simulation set,
whereas none of the replicates from the Tier II strains (92UG037 and JR-CSF) did
so. Docking repeat unit microspecies to the gp120 protein before and after MD
simulation enabled identification of residues that were key for binding. Notably,
only a few residues were found to be important for docking both before and after
MD simulation as a result of the conformational heterogeneity provided by the
simulations. Consideration of the residues that were consistently involved in
interactions with the ligand revealed the importance of both hydrophilic and
hydrophobic moieties of the ligand for effective binding. The results also
suggest that polymers of DCSti-alt-MA with repeating units of different
configurations may have advantages for therapeutic efficacy.
PMID- 29346394
TI - Decision time and confidence predict choosers' identification performance in
photographic showups.
AB - In vast contrast to the multitude of lineup studies that report on the link
between decision time, confidence, and identification accuracy, only a few
studies looked at these associations for showups, with results varying widely
across studies. We therefore set out to test the individual and combined value of
decision time and post-decision confidence for diagnosing the accuracy of
positive showup decisions using confidence-accuracy characteristic curves and
Bayesian analyses. Three-hundred-eighty-four participants viewed a stimulus event
and were subsequently presented with two showups which could be target-present or
target-absent. As expected, we found a negative decision time-accuracy and a
positive post-decision confidence-accuracy correlation for showup selections.
Confidence-accuracy characteristic curves demonstrated the expected additive
effect of combining both postdictors. Likewise, Bayesian analyses, taking into
account all possible target-presence base rate values showed that fast and
confident identification decisions were more diagnostic than slow or less
confident decisions, with the combination of both being most diagnostic for
postdicting accurate and inaccurate decisions. The postdictive value of decision
time and post-decision confidence was higher when the prior probability that the
suspect is the perpetrator was high compared to when the prior probability that
the suspect is the perpetrator was low. The frequent use of showups in practice
emphasizes the importance of these findings for court proceedings. Overall, these
findings support the idea that courts should have most trust in showup
identifications that were made fast and confidently, and least in showup
identifications that were made slowly and with low confidence.
PMID- 29346395
TI - Evaluation of participatory teaching methods in undergraduate medical students'
learning along the first academic courses.
AB - The European Higher Education Area (EHEA) is an opportunity to redesign medical
education. Academic training is now focused on acquiring not only knowledge, but
also those competencies critical to face complex professional scenarios. Together
with re-evaluating traditional teaching methods, EHEA has forced a technological
shift in the way we teach. By critically assessing the impact of novel teaching
methodologies, we can better define biomedical education demands. Here, we
address this question on a sample of medical students instructed in basic
subjects along the first two academic courses. Two hundred and one medical
students participated in the study (n = 128 first year, n = 73 second year).
Quantitative (conventional survey statistics) and qualitative (open coding)
approaches were combined to analyze data from surveys, confidential
questionnaires, semi-structured interviews and open discussion. First year
medical students rated more positively the use of participatory methodologies
than second year students. A major drawback is detected in the perceived
workload. Active teaching methodologies show a strong reliance on their time of
implementation for medical students, a key aspect to be considered in the design
of integrative participatory curricula along the first academic courses.
PMID- 29346396
TI - Serum miRNA levels are related to glucose homeostasis and islet autoantibodies in
children with high risk for type 1 diabetes.
AB - Micro RNAs (miRNAs) are promising disease biomarkers due to their high stability.
Their expression in serum is altered in type 1 diabetes, but whether deviations
exist in individuals with high risk for type 1 diabetes remains unexplored. We
therefore assessed serum miRNAs in high-risk individuals (n = 21) positive for
multiple islet autoantibodies, age-matched healthy children (n = 17) and recent
onset type 1 diabetes patients (n = 8), using Serum/Plasma Focus microRNA PCR
Panels from Exiqon. The miRNA levels in the high-risk group were similar to
healthy controls, and no specific miRNA profile was identified for the high-risk
group. However, serum miRNAs appeared to reflect glycemic status and ongoing
islet autoimmunity in high-risk individuals, since several miRNAs were associated
to glucose homeostasis and autoantibody titers. High-risk individuals progressing
to clinical disease after the sampling could not be clearly distinguished from
non-progressors, while miRNA expression in the type 1 diabetes group deviated
significantly from high-risk individuals and healthy controls, perhaps explained
by major metabolic disturbances around the time of diagnosis.
PMID- 29346397
TI - Dose enhancement effects of gold nanoparticles specifically targeting RNA in
breast cancer cells.
AB - Localization microscopy has shown to be capable of systematic investigations on
the arrangement and counting of cellular uptake of gold nanoparticles (GNP) with
nanometer resolution. In this article, we show that the application of specially
modified RNA targeting gold nanoparticles ("SmartFlares") can result in ring like
shaped GNP arrangements around the cell nucleus. Transmission electron microscopy
revealed GNP accumulation in vicinity to the intracellular membrane structures
including them of the endoplasmatic reticulum. A quantification of the radio
therapeutic dose enhancement as a proof of principle was conducted with gammaH2AX
foci analysis: The application of both-SmartFlares and unmodified GNPs-lead to a
significant dose enhancement with a factor of up to 1.2 times the dose deposition
compared to non-treated breast cancer cells. This enhancement effect was even
more pronounced for SmartFlares. Furthermore, it was shown that a magnetic field
of 1 Tesla simultaneously applied during irradiation has no detectable influence
on neither the structure nor the dose enhancement dealt by gold nanoparticles.
PMID- 29346398
TI - Dual function of EDTA with silver nanoparticles for root canal treatment-A novel
modification.
AB - The chelating and antimicrobial capacity of a novel modification of 17% EDTA with
silver nanoparticles (AgNPs) (EDTA-AgNPs) was evaluated in-vitro for root canal
treatment (RCT). The EDTA-AgNPs solution was characterized by UV-Vis
spectroscopy, zeta-potential and high-resolution transmission electron microscopy
(HRTEM). Antimicrobial capacity was evaluated against Candida albicans and
Staphylococcus aureus in planktonic and biofilm cells by broth macrodilution (24
h) and XTT assays, (1, 10 and 30 min) respectively. The chelating capacity of
EDTA-AgNPs was assessed indirectly (smear layer removal) and directly
(demineralizing effect) in bovine dentin at two silver concentrations, 16 and 512
MUg/ml at 1 and 10 minutes of exposure time. Smear layer removal was evaluated by
atomic force microscopy (AFM) and scanning electron microscopy (SEM). The
demineralizing effect was determined by atomic absorption spectroscopy (AAS),
microhardness test (MH) and X-ray diffractometer (XRD). Synthesized AgNPs were
quasi-spherical in shape with an average size of 13.09 +/- 8.05 nm. 17% EDTA
AgNPs was effective to inhibit C. albicans and S. aureus in planktonic and
biofilm cultures. The smear layer removal and demineralizing effect were similar
between 17% EDTA-AgNPs and 17% EDTA treatments. The 17% EDTA-AgNPs solution
proved to be an effective antimicrobial agent, and has a similar chelating
capacity to 17% EDTA alone. These in-vitro studies strongly suggest that EDTA
AgNPs could be used for effective smear layer removal, having an antimicrobial
effect at the same time during RCT.
PMID- 29346399
TI - The motivation-based calving facility: Social and cognitive factors influence
isolation seeking behaviour of Holstein dairy cows at calving.
AB - In order to improve animal welfare it is recommended that dairy farmers move
calving cows from the herd to individual pens when calving is imminent. However,
the practicality of moving cows has proven a challenge and may lead to
disturbance of the cows rather than easing the process of calving. One solution
may be to allow the cow to seek isolation prior to calving. This study examined
whether pre-parturient dairy cows will isolate in an individual calving pen
placed in a group calving setting and whether a closing gate in this individual
calving pen will cause more cows to isolate prior to calving. Danish Holstein
cows (n = 66) were housed in groups of six in a group pen with access to six
individual calving pens connected to the group area. Cows were trained to use one
of two isolation opportunities i.e. individual calving pens with functional
closing gates (n = 35) allowing only one cow access at a time, or individual
calving pens with permanently open gates allowing free cow traffic between group
area and individual pen (n = 31). The response variables were calving site,
calving behaviour and social behaviour. Unexpectedly, a functional gate did not
facilitate isolation seeking, perhaps because the cows were not able to combine a
learnt response with the motivation to isolate. Dominant cows had the highest
chance of calving in an individual calving pen. If an alien calf was present in
the group pen or any of the individual pens, cows were less likely to calve in an
individual calving pen. Future studies should allow cows easy access to an
individual calving pen and explore what motivates pre-parturient cows to seek
isolation in order to facilitate voluntary use of individual calving pens.
PMID- 29346400
TI - The mechanisms how heparin affects the tumor cell induced VEGF and chemokine
release from platelets to attenuate the early metastatic niche formation.
AB - Metastasis is responsible for the majority of cancer associated fatalities. Tumor
cells leaving the primary tumor and entering the blood flow immediately interact
with platelets. Activated platelets contribute in different ways to cancer cell
survival and proliferation, e.g. in formation of the early metastatic niche by
release of different growth factors and chemokines. Here we show that a direct
interaction between platelets and MV3 melanoma or MCF7 breast cancer cells
induces platelet activation and a VEGF release in citrated plasma that cannot be
further elevated by the coagulation cascade and generated thrombin. In contrast,
the release of platelet-derived chemokines CXCL5 and CXCL7 depends on both, a
thrombin-mediated platelet activation and a direct interaction between tumor
cells and platelets. Preincubation of platelets with therapeutic concentrations
of unfractionated heparin reduces the tumor cell initiated VEGF release from
platelets. In contrast, tumor cell induced CXCL5 and CXCL7 release from platelets
was not impacted by heparin pretreatment in citrated plasma. In defibrinated,
recalcified plasma, on the contrary, heparin is able to reduce CXCL5 and CXCL7
release from platelets by thrombin inhibition. Our data indicate that different
chemokines and growth factors in diverse platelet granules are released in
tightly regulated processes by various trigger mechanisms. We show for the first
time that heparin is able to reduce the mediator release induced by different
tumor cells both in a contact and coagulation dependent manner.
PMID- 29346401
TI - CD1d deficiency inhibits the development of abdominal aortic aneurysms in LDL
receptor deficient mice.
AB - An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta leading
to serious complications and mostly to death. AAA development is associated with
an accumulation of inflammatory cells in the aorta including NKT cells. An
important factor in promoting the recruitment of these inflammatory cells into
tissues and thereby contributing to the development of AAA is angiotensin II (Ang
II). We demonstrate that a deficiency in CD1d dependent NKT cells under
hyperlipidemic conditions (LDLr-/-CD1d-/- mice) results in a strong decline in
the severity of angiotensin II induced aneurysm formation when compared with LDLr
/- mice. In addition, we show that Ang II amplifies the activation of NKT cells
both in vivo and in vitro. We also provide evidence that type I NKT cells
contribute to AAA development by inducing the expression of matrix degrading
enzymes in vSMCs and macrophages, and by cytokine dependently decreasing vSMC
viability. Altogether, these data prove that CD1d-dependent NKT cells contribute
to AAA development in the Ang II-mediated aneurysm model by enhancing aortic
degradation, establishing that therapeutic applications which target NKT cells
can be a successful way to prevent AAA development.
PMID- 29346402
TI - Gene regulation in Kluyveromyces marxianus in the context of chromosomes.
AB - Eukaryotes, including the unicellular eukaryotes such as yeasts, employ multiple
levels of gene regulation. Regulation of chromatin structure through chromatin
compaction cascades, and influenced by transcriptional insulators, might play a
role in the coordinated regulation of genes situated at adjacent loci and
expressed as a co-regulated cluster. Subtelomeric gene silencing, which has
previously been described in the yeast Saccharomyces cerevisiae, is an example of
this phenomenon. Transcription from a common regulatory element located around a
shared intergenic region is another factor that could coordinate the
transcription of genes at adjacent loci. Additionally, the presence of DNA
binding sites for the same transcription factor may coordinate expression of
multiple genes. Yeasts such as the industrially important Kluyveromyces marxianus
may also display these modes of regulation, but this has not been explored to
date. An exploration was done using a complete genome and RNA-seq data from a
previous study of the transcriptional response to glucose or xylose as the carbon
source in a defined culture medium, and investigating whether the species
displays clusters of co-localised differentially expressed genes. Regions of
possible subtelomeric silencing were evident, but were non-responsive to the
carbon sources tested here. Additionally, glucose or xylose responsive clusters
were discovered far from telomeres which contained some of the most significantly
differentially expressed genes, encoding enzymes involved in the utilisation of
alternative carbon sources such as the industrially important inulinase gene
INU1. These clusters contained putative binding sites for the carbon source
responsive transcription factors Mig1 and Adr1. Additionally, we investigated the
potential contribution of common intergenic regions in co-regulation. Some
observations were also made in terms of the evolutionary conservation of these
clusters among yeast species and the presence of potential transcriptional
insulators at the periphery of these clusters.
PMID- 29346403
TI - Prime incision: A minimally invasive approach to breast cancer surgical treatment
A 2 cohort retrospective comparison with conventional breast conserving surgery.
AB - The prime incision technique is an oncoplastic surgery aimed to remove both the
breast tumor and the sentinel lymph node through one incision, thus providing
better aesthetic results than the conventional breast conservative two incision
technique. We retrospectively evaluated 2 cohorts of 60 consecutive breast cancer
patients operated by either conventional breast conservative surgery (N = 26) or
one incision surgery (N = 34). There were no recurrence or death events observed
in any group. No difference was seen regarding the incidence of surgical
complications. In the prime incision group the breast volume removed was
significantly lower than in the conventional surgery group as well as was the
surgical time and the number of dissected lymph nodes. Aesthetical results were
better in the one incision group. Further prospective studies are needed to
validate the one incision technique as a surgical option for selected early stage
breast cancer patients.
PMID- 29346404
TI - Bio-fortification potential of global wild annual lentil core collection.
AB - Lentil, generally known as poor man's' meat due to its high protein value is also
a good source of dietary fiber, antioxidants and vitamins along with fast cooking
characteristics. It could be used globally as a staple food crop to eradicate
hidden hunger, if this nutritionally rich crop is further enriched with essential
minerals. This requires identification of essential mineral rich germplasm. So,
in the present study, a core set of 96 wild accessions extracted from 405 global
wild annual collections comprising different species was analyzed to determine
its bio-fortification potential. Impressive variation (mg/100 g) was observed for
different minerals including Na (30-318), K (138.29-1578), P (37.50-593.75), Ca
(4.74-188.75), Mg (15-159), Fe (2.82-14.12), Zn (1.29-12.62), Cu (0.5-7.12), Mn
(1.22-9.99), Mo (1.02-11.89), Ni (0.16-3.49), Pb (0.01-0.58), Cd (0-0.03), Co (0
0.63) and As (0-0.02). Hierarchical clustering revealed high intra- and inter
specific variability. Further, correlation study showed positive significant
association among minerals and between minerals including agro-morphological
traits. Accessions representation from Turkey and Syria had maximum variability
for different minerals. Diversity analysis exhibited wide geographical variations
across gene-pool in core set. Potential use of the identified trait-specific
genetic resources could be initial genetic material, for genetic base broadening
and biofortification of cultivated lentil.
PMID- 29346406
TI - Shea (Vitellaria paradoxa Gaertn C. F.) fruit yield assessment and management by
farm households in the Atacora district of Benin.
AB - Vitellaria paradoxa (Gaertn C. F.), or shea tree, remains one of the most
valuable trees for farmers in the Atacora district of northern Benin, where rural
communities depend on shea products for both food and income. To optimize
productivity and management of shea agroforestry systems, or "parklands,"
accurate and up-to-date data are needed. For this purpose, we monitored120
fruiting shea trees for two years under three land-use scenarios and different
soil groups in Atacora, coupled with a farm household survey to elicit
information on decision making and management practices. To examine the local
pattern of shea tree productivity and relationships between morphological factors
and yields, we used a randomized branch sampling method and applied a regression
analysis to build a shea yield model based on dendrometric, soil and land-use
variables. We also compared potential shea yields based on farm household socio
economic characteristics and management practices derived from the survey data.
Soil and land-use variables were the most important determinants of shea fruit
yield. In terms of land use, shea trees growing on farmland plots exhibited the
highest yields (i.e., fruit quantity and mass) while trees growing on Lixisols
performed better than those of the other soil group. Contrary to our
expectations, dendrometric parameters had weak relationships with fruit yield
regardless of land-use and soil group. There is an inter-annual variability in
fruit yield in both soil groups and land-use type. In addition to observed inter
annual yield variability, there was a high degree of variability in production
among individual shea trees. Furthermore, household socioeconomic characteristics
such as road accessibility, landholding size, and gross annual income influence
shea fruit yield. The use of fallow areas is an important land management
practice in the study area that influences both conservation and shea yield.
PMID- 29346405
TI - Oxytocin alters cell fate selection of rat neural progenitor cells in vitro.
AB - Synthetic oxytocin (sOT) is widely used during labor, yet little is known about
its effects on fetal brain development despite evidence that it reaches the fetal
circulation. Here, we tested the hypothesis that sOT would affect early
neurodevelopment by investigating its effects on neural progenitor cells (NPC)
from embryonic day 14 rat pups. NPCs expressed the oxytocin receptor (OXTR),
which was downregulated by 45% upon prolonged treatment with sOT. Next, we
examined the effects of sOT on NPC death, apoptosis, proliferation, and
differentiation using antibodies to NeuN (neurons), Olig2 (oligodendrocytes), and
GFAP (astrocytes). Treated NPCs were analysed with unbiased high-throughput
immunocytochemistry. Neither 6 nor 24 h exposure to 100 pM or 100 nM sOT had an
effect on viability as assessed by PI or CC-3 immunocytochemistry. Similarly, sOT
had negligible effect on NPC proliferation, except that the overall rate of NPC
proliferation was higher in the 24 h compared to the 6 h group regardless of sOT
exposure. The most significant finding was that sOT exposure caused NPCs to
select a predominantly neuronal lineage, along with a concomitant decrease in
glial cells. Collectively, our data suggest that perinatal exposure to sOT can
have neurodevelopmental consequences for the fetus, and support the need for in
vivo anatomical and behavioral studies in offspring exposed to sOT in utero.
PMID- 29346408
TI - Long lasting insecticidal bed nets ownership, access and use in a high malaria
transmission setting before and after a mass distribution campaign in Uganda.
AB - INTRODUCTION: Uganda is conducting a second mass LLIN distribution campaign and
Katakwi district recently received LLINs as part of this activity. This study was
conducted to measure the success of the campaign in this setting, an area of high
transmission, with the objectives to estimate LLIN ownership, access and use pre
and post campaign implementation. METHODS: Two identical cross sectional surveys,
based on the Malaria Indicator Survey methodology, were conducted in three sub
counties in this district (Kapujan, Magoro and Toroma), six months apart, one
before and another after the mass distribution campaign. Data on three main LLIN
indicators including; household LLIN ownership, population with access to an LLIN
and use were collected using a household and a women's questionnaire identical to
the Malaria Indicator Survey. RESULTS: A total of 601 and 607 households were
randomly selected in survey one and two respectively. At baseline, 60.57% (56.53
64.50) of households owned at least one net for every two persons who stayed in
the household the night before the survey which significantly increased to 70.35%
(66.54-73.96) after the campaign (p = 0.001). Similarly, the percentage of the
household population with access to an LLIN significantly increased from 84.76%
(82.99-86.52) to 91.57% (90.33-92.81), p = 0.001 and the percentage of household
population that slept under an LLIN the night before the survey also
significantly increased from 56.85% (55.06-58.82) to 81.72% (76.75-83.21), p =
0.001. CONCLUSION: The LLIN mass campaign successfully achieved the national
target of over eighty-five percent of the population with access to an LLIN in
this setting, however, universal household coverage and use were fourteen and
three percent points less than the national target respectively. This is useful
for malaria programs to consider during the planning of future campaigns by
tailoring efforts around deficient areas like mechanisms to increase universal
coverage and behavior change communication.
PMID- 29346407
TI - Relaxin reverses inflammatory and immune signals in aged hearts.
AB - BACKGROUND: 'Healthy' aging drives structural and functional changes in the heart
including maladaptive electrical remodeling, fibrosis and inflammation, which
lower the threshold for cardiovascular diseases such as heart failure (HF) and
atrial fibrillation (AF). Despite mixed results in recent clinical trials,
Relaxin-therapy for 2-days could reduce mortality by 37% at 180-days post
treatment, in patients with acute decompensated HF. Relaxin's short life-span
(hours) but long-lasting protective actions led us to test the hypothesis that
relaxin acts at a genomic level to reverse maladaptive remodeling in aging and
HF. METHODS AND RESULTS: Young (9-month) and aged (24-month), male and female F
344/Brown Norway rats were treated with relaxin (0.4 mg/kg/day) for 2-weeks
delivered by subcutaneous osmotic mini-pumps or with sodium acetate (controls).
The genomic effects of aging and relaxin were evaluated by extracting RNA from
the left ventricles and analyzing genomic changes by RNA-sequencing, Ingenuity
Pathway Analysis, MetaCore and tissue immunohistochemistry. We found that aging
promotes a native inflammatory response with distinct sex-differences and relaxin
suppresses transcription of multiple genes and signaling pathways associated with
inflammation and HF in both genders. In addition, aging significantly increased:
macrophage infiltration and atrial natriuretic peptide levels in female
ventricles, and activation of the complement cascade, whereas relaxin reversed
these age-related effects. CONCLUSION: These data support the hypothesis that
relaxin alters gene transcription and suppresses inflammatory pathways and genes
associated with HF and aging. Relaxin's suppression of inflammation and fibrosis
supports its potential as a therapy for cardiovascular and inflammation-related
diseases, such as HF, AF and diabetes.
PMID- 29346410
TI - An evaluation of multi-probe locality sensitive hashing for computing
similarities over web-scale query logs.
AB - Many modern applications of AI such as web search, mobile browsing, image
processing, and natural language processing rely on finding similar items from a
large database of complex objects. Due to the very large scale of data involved
(e.g., users' queries from commercial search engines), computing such near or
nearest neighbors is a non-trivial task, as the computational cost grows
significantly with the number of items. To address this challenge, we adopt
Locality Sensitive Hashing (a.k.a, LSH) methods and evaluate four variants in a
distributed computing environment (specifically, Hadoop). We identify several
optimizations which improve performance, suitable for deployment in very large
scale settings. The experimental results demonstrate our variants of LSH achieve
the robust performance with better recall compared with "vanilla" LSH, even when
using the same amount of space.
PMID- 29346409
TI - Prediction of absolute risk of acute graft-versus-host disease following
hematopoietic cell transplantation.
AB - Allogeneic hematopoietic cell transplantation (HCT) is the treatment of choice
for a variety of hematologic malignancies and disorders. Unfortunately, acute
graft-versus-host disease (GVHD) is a frequent complication of HCT. While
substantial research has identified clinical, genetic and proteomic risk factors
for acute GVHD, few studies have sought to develop risk prediction tools that
quantify absolute risk. Such tools would be useful for: optimizing donor
selection; guiding GVHD prophylaxis, post-transplant treatment and monitoring
strategies; and, recruitment of patients into clinical trials. Using data on
9,651 patients who underwent first allogeneic HLA-identical sibling or unrelated
donor HCT between 01/1999-12/2011 for treatment of a hematologic malignancy, we
developed and evaluated a suite of risk prediction tools for: (i) acute GVHD
within 100 days post-transplant and (ii) a composite endpoint of acute GVHD or
death within 100 days post-transplant. We considered two sets of inputs: (i)
clinical factors that are typically readily-available, included as main effects;
and, (ii) main effects combined with a selection of a priori specified two-way
interactions. To build the prediction tools we used the super learner, a recently
developed ensemble learning statistical framework that combines results from
multiple other algorithms/methods to construct a single, optimal prediction tool.
Across the final super learner prediction tools, the area-under-the curve (AUC)
ranged from 0.613-0.640. Improving the performance of risk prediction tools will
likely require extension beyond clinical factors to include biological variables
such as genetic and proteomic biomarkers, although the measurement of these
factors may currently not be practical in standard clinical settings.
PMID- 29346411
TI - Evaluation of Hirst-type spore traps in outdoor Aspergillaceae monitoring during
large demolition work in hospital.
AB - Demolition can generate fungal spore suspensions in association with various
adverse health effects, such as high risk of invasive aspergillosis in
immunocompromised patients. One block of Edouard Herriot Hospital was entirely
demolished. The aim of the present study was to evaluate Hirst-type spore traps
utility in monitoring outdoor Aspergillaceae (Aspergillus spp. + Penicillium
spp.) spores in part of Edouard Herriot Hospital (Lyon, France) undergoing major
demolition. Three periods were scheduled in 2015: (A) Gutting of building and
asbestos removal, (B) Demolition of floors, (C) Excavation and earthwork. Outdoor
Aspergillaceae fungal load was monitored by cultivable (Air Ideal(r), bioMerieux)
and non-cultivable methods (Lanzoni VPPS-2000, Analyzair(r), Bologna, Italy).
Differences of Aspergillaceae recorded with Hirst-type spore traps were observed
between Gerland and Edouard Herriot Hospital. Differences between Aspergillaceae
were recorded between day time and night time at Gerland and Edouard Herriot
Hospital. Daily paired differences between Aspergillaceae recorded with non
cultivable methodology at Edouard Herriot Hospital and in an area without
demolition work were significant in Period A vs Period B (p = 10-4) and Period A
vs Period C (p = 10-4). Weak correlation of daily Aspergillaceae recorded by both
methods at Edouard Herriot Hospital was significant only for Period C (r = 0.26,
p = 0.048, n = 58). Meteorological parameters and type of demolition works were
found to heavily influenced Aspergillaceae dispersion. Non-cultivable methodology
is a promising tool for outdoor Aspergillaceae scrutiny during major demolition
work in hospital, helping infection control staff to rapidly implement control
measures.
PMID- 29346412
TI - A comparative analysis of preservation techniques for the optimal molecular
detection of hookworm DNA in a human fecal specimen.
AB - BACKGROUND: Proper collection and storage of fecal samples is necessary to
guarantee the subsequent reliability of DNA-based soil-transmitted helminth
diagnostic procedures. Previous research has examined various methods to preserve
fecal samples for subsequent microscopic analysis or for subsequent determination
of overall DNA yields obtained following DNA extraction. However, only limited
research has focused on the preservation of soil-transmitted helminth DNA in
stool samples stored at ambient temperature or maintained in a cold chain for
extended periods of time. METHODOLOGY: Quantitative real-time PCR was used in
this study as a measure of the effectiveness of seven commercially available
products to preserve hookworm DNA over time and at different temperatures.
Results were compared against "no preservative" controls and the "gold standard"
of rapidly freezing samples at -20 degrees C. The preservation methods were
compared at both 4 degrees C and at simulated tropical ambient temperature (32
degrees C) over a period of 60 days. Evaluation of the effectiveness of each
preservative was based on quantitative real-time PCR detection of target hookworm
DNA. CONCLUSIONS: At 4 degrees C there were no significant differences in DNA
amplification efficiency (as measured by Cq values) regardless of the
preservation method utilized over the 60-day period. At 32 degrees C,
preservation with FTA cards, potassium dichromate, and a silica bead two-step
desiccation process proved most advantageous for minimizing Cq value increases,
while RNA later, 95% ethanol and Paxgene also demonstrate some protective effect.
These results suggest that fecal samples spiked with known concentrations of
hookworm-derived egg material can remain at 4 degrees C for 60 days in the
absence of preservative, without significant degradation of the DNA target.
Likewise, a variety of preservation methods can provide a measure of protection
in the absence of a cold chain. As a result, other factors, such as preservative
toxicity, inhibitor resistance, preservative cost, shipping requirements, sample
infectivity, and labor costs should be considered when deciding upon an
appropriate method for the storage of fecal specimens for subsequent PCR
analysis. Balancing logistical factors and the need to preserve the target DNA,
we believe that under most circumstances 95% ethanol provides the most pragmatic
choice for preserving stool samples in the field.
PMID- 29346413
TI - Genetic diversity and potential routes of transmission of Mycobacterium bovis in
Mozambique.
AB - Bovine tuberculosis is a zoonotic disease with largely unknown impact in Africa,
with risk factors such as HIV and direct contact with animals or consumption of
Mycobacterium bovis infected animal products. In order to understand and quantify
this risk and design intervention strategies, good epidemiological studies are
needed. Such studies can include molecular typing of M. bovis isolates. The aim
of this study was to apply these tools to provide novel information concerning
the distribution of bovine tuberculosis in cattle in Mozambique and thereby
provide relevant information to guide policy development and strategies to
contain the disease in livestock, and reduce the risk associated with
transmission to humans. A collection of 178 M. bovis isolates was obtained from
cattle in Mozambique. Using spoligotyping and regions of difference analysis, we
classified the isolates into clonal complexes, thus reporting the first
characterisation of M. bovis strains in this region. Data from MIRU-VNTR typing
was used to compare isolates from a number of African countries, revealing a
deeply geographically structured diversity of M. bovis. Eastern Africa appears to
show high diversity, suggesting deep evolution in that region. The diversity of
M. bovis in Africa does not seem to be a function of recent importation of
animals, but is probably maintained within each particular region by constant
reinfection from reservoir animals. Understanding the transmission routes of M.
bovis in Mozambique and elsewhere is essential in order to focus public health
and veterinary resources to contain bovine tuberculosis.
PMID- 29346414
TI - Reliability of plasma polar metabolite concentrations in a large-scale cohort
study using capillary electrophoresis-mass spectrometry.
AB - BACKGROUND: Cohort studies with metabolomics data are becoming more widespread,
however, large-scale studies involving 10,000s of participants are still limited,
especially in Asian populations. Therefore, we started the Tsuruoka Metabolomics
Cohort Study enrolling 11,002 community-dwelling adults in Japan, and using
capillary electrophoresis-mass spectrometry (CE-MS) and liquid chromatography
mass spectrometry. The CE-MS method is highly amenable to absolute quantification
of polar metabolites, however, its reliability for large-scale measurement is
unclear. The aim of this study is to examine reproducibility and validity of
large-scale CE-MS measurements. In addition, the study presents absolute
concentrations of polar metabolites in human plasma, which can be used in future
as reference ranges in a Japanese population. METHODS: Metabolomic profiling of
8,413 fasting plasma samples were completed using CE-MS, and 94 polar metabolites
were structurally identified and quantified. Quality control (QC) samples were
injected every ten samples and assessed throughout the analysis. Inter- and intra
batch coefficients of variation of QC and participant samples, and technical
intraclass correlation coefficients were estimated. Passing-Bablok regression of
plasma concentrations by CE-MS on serum concentrations by standard clinical
chemistry assays was conducted for creatinine and uric acid. RESULTS AND
CONCLUSIONS: In QC samples, coefficient of variation was less than 20% for 64
metabolites, and less than 30% for 80 metabolites out of the 94 metabolites.
Inter-batch coefficient of variation was less than 20% for 81 metabolites.
Estimated technical intraclass correlation coefficient was above 0.75 for 67
metabolites. The slope of Passing-Bablok regression was estimated as 0.97 (95%
confidence interval: 0.95, 0.98) for creatinine and 0.95 (0.92, 0.96) for uric
acid. Compared to published data from other large cohort measurement platforms,
reproducibility of metabolites common to the platforms was similar to or better
than in the other studies. These results show that our CE-MS platform is suitable
for conducting large-scale epidemiological studies.
PMID- 29346415
TI - Acute multi-sgRNA knockdown of KEOPS complex genes reproduces the microcephaly
phenotype of the stable knockout zebrafish model.
AB - Until recently, morpholino oligonucleotides have been widely employed in
zebrafish as an acute and efficient loss-of-function assay. However, off-target
effects and reproducibility issues when compared to stable knockout lines have
compromised their further use. Here we employed an acute CRISPR/Cas approach
using multiple single guide RNAs targeting simultaneously different positions in
two exemplar genes (osgep or tprkb) to increase the likelihood of generating
mutations on both alleles in the injected F0 generation and to achieve a similar
effect as morpholinos but with the reproducibility of stable lines. This multi
single guide RNA approach resulted in median likelihoods for at least one
mutation on each allele of >99% and sgRNA specific insertion/deletion profiles as
revealed by deep-sequencing. Immunoblot showed a significant reduction for Osgep
and Tprkb proteins. For both genes, the acute multi-sgRNA knockout recapitulated
the microcephaly phenotype and reduction in survival that we observed previously
in stable knockout lines, though milder in the acute multi-sgRNA knockout.
Finally, we quantify the degree of mutagenesis by deep sequencing, and provide a
mathematical model to quantitate the chance for a biallelic loss-of-function
mutation. Our findings can be generalized to acute and stable CRISPR/Cas
targeting for any zebrafish gene of interest.
PMID- 29346416
TI - Decoding the network of Trypanosoma brucei proteins that determines sensitivity
to apolipoprotein-L1.
AB - In contrast to Trypanosoma brucei gambiense and T. b. rhodesiense (the causative
agents of human African trypanosomiasis), T. b. brucei is lysed by apolipoprotein
L1 (apoL1)-containing human serum trypanolytic factors (TLF), rendering it non
infectious to humans. While the mechanisms of TLF1 uptake, apoL1 membrane
integration, and T. b. gambiense and T. b. rhodesiense apoL1-resistance have been
extensively characterised, our understanding of the range of factors that drive
apoL1 action in T. b. brucei is limited. Selecting our bloodstream-form T. b.
brucei RNAi library with recombinant apoL1 identified an array of factors that
supports the trypanocidal action of apoL1, including six putative ubiquitin
modifiers and several proteins putatively involved in membrane trafficking; we
also identified the known apoL1 sensitivity determinants, TbKIFC1 and the V
ATPase. Most prominent amongst the novel apoL1 sensitivity determinants was a
putative ubiquitin ligase. Intriguingly, while loss of this ubiquitin ligase
reduces parasite sensitivity to apoL1, its loss enhances parasite sensitivity to
TLF1-dominated normal human serum, indicating that free and TLF1-bound apoL1 have
contrasting modes-of-action. Indeed, loss of the known human serum sensitivity
determinants, p67 (lysosomal associated membrane protein) and the cathepsin-L
regulator, 'inhibitor of cysteine peptidase', had no effect on sensitivity to
free apoL1. Our findings highlight a complex network of proteins that influences
apoL1 action, with implications for our understanding of the anti-trypanosomal
action of human serum.
PMID- 29346417
TI - Xylose donor transport is critical for fungal virulence.
AB - Cryptococcus neoformans, an AIDS-defining opportunistic pathogen, is the leading
cause of fungal meningitis worldwide and is responsible for hundreds of thousands
of deaths annually. Cryptococcal glycans are required for fungal survival in the
host and for pathogenesis. Most glycans are made in the secretory pathway,
although the activated precursors for their synthesis, nucleotide sugars, are
made primarily in the cytosol. Nucleotide sugar transporters are membrane
proteins that solve this topological problem, by exchanging nucleotide sugars for
the corresponding nucleoside phosphates. The major virulence factor of C.
neoformans is an anti-phagocytic polysaccharide capsule that is displayed on the
cell surface; capsule polysaccharides are also shed from the cell and impede the
host immune response. Xylose, a neutral monosaccharide that is absent from model
yeast, is a significant capsule component. Here we show that Uxt1 and Uxt2 are
both transporters specific for the xylose donor, UDP-xylose, although they
exhibit distinct subcellular localization, expression patterns, and kinetic
parameters. Both proteins also transport the galactofuranose donor, UDP
galactofuranose. We further show that Uxt1 and Uxt2 are required for xylose
incorporation into capsule and protein; they are also necessary for C. neoformans
to cause disease in mice, although surprisingly not for fungal viability in the
context of infection. These findings provide a starting point for deciphering the
substrate specificity of an important class of transporters, elucidate a
synthetic pathway that may be productively targeted for therapy, and contribute
to our understanding of fundamental glycobiology.
PMID- 29346418
TI - The relationship of lung function with ambient temperature.
AB - BACKGROUND: Lung function is complex trait with both genetic and environmental
factors contributing to variation. It is unknown how geographic factors such as
climate affect population respiratory health. OBJECTIVE: To determine whether
ambient air temperature is associated with lung function (FEV1) in the general
population. DESIGN/SETTING: Associations between spirometry data from two
National Health and Nutrition Examination Survey (NHANES) periods representative
of the U.S. non-institutionalized population and mean annual ambient temperature
were assessed using survey-weighted multivariate regression.
PARTICIPANTS/MEASUREMENTS: The NHANES III (1988-94) cohort included 14,088
individuals (55.6% female) and the NHANES 2007-12 cohort included 14,036
individuals (52.3% female), with mean ages of 37.4+/-23.4 and 34.4+/-21.8 years
old and FEV1 percent predicted values of 99.8+/-15.8% and 99.2+/-14.5%,
respectively. RESULTS: After adjustment for confounders, warmer ambient
temperatures were associated with lower lung function in both cohorts (NHANES III
p = 0.020; NHANES 2007-2012 p = 0.014). The effect was similar in both cohorts
with a 0.71% and 0.59% predicted FEV1 decrease for every 10 degrees F increase in
mean temperature in the NHANES III and NHANES 2007-2012 cohorts, respectively.
This corresponds to ~2 percent predicted difference in FEV1 between the warmest
and coldest regions in the continental United States. CONCLUSIONS: In the general
U.S. population, residing in regions with warmer ambient air temperatures was
associated with lower lung function with an effect size similar to that of
traffic pollution. Rising temperatures associated with climate change could have
effects on pulmonary function in the general population.
PMID- 29346419
TI - SAXS analysis of a soluble cytosolic NgBR construct including extracellular and
transmembrane domains.
AB - The Nogo-B receptor (NgBR) is involved in oncogenic Ras signaling through
directly binding to farnesylated Ras. It recruits farnesylated Ras to the non
lipid-raft membrane for interaction with downstream effectors. However, the
cytosolic domain of NgBR itself is only partially folded. The lack of several
conserved secondary structural elements makes this domain unlikely to form a
complete farnesyl binding pocket. We find that inclusion of the extracellular and
transmembrane domains that contain additional conserved residues to the cytosolic
region results in a well folded protein with a similar size and shape to the
E.coli cis-isoprenyl transferase (UPPs). Small Angle X-ray Scattering (SAXS)
analysis reveals the radius of gyration (Rg) of our NgBR construct to be 18.2 A
with a maximum particle dimension (Dmax) of 61.0 A. Ab initio shape modeling
returns a globular molecular envelope with an estimated molecular weight of 23.0
kD closely correlated with the calculated molecular weight. Both Kratky plot and
pair distribution function of NgBR scattering reveal a bell shaped peak which is
characteristic of a single globularly folded protein. In addition, circular
dichroism (CD) analysis reveals that our construct has the secondary structure
contents similar to the UPPs. However, this result does not agree with the
currently accepted topological orientation of NgBR which might partition this
construct into three separate domains. This discrepancy suggests another possible
NgBR topology and lends insight into a potential molecular basis of how NgBR
facilitates farnesylated Ras recruitment.
PMID- 29346420
TI - Initial acquisition and succession of the cystic fibrosis lung microbiome is
associated with disease progression in infants and preschool children.
AB - The cystic fibrosis (CF) lung microbiome has been studied in children and adults;
however, little is known about its relationship to early disease progression. To
better understand the relationship between the lung microbiome and early
respiratory disease, we characterized the lower airways microbiome using
bronchoalveolar lavage (BAL) samples obtained from clinically stable CF infants
and preschoolers who underwent bronchoscopy and chest computed tomography (CT).
Cross-sectional samples suggested a progression of the lower airways microbiome
with age, beginning with relatively sterile airways in infancy. By age two,
bacterial sequences typically associated with the oral cavity dominated lower
airways samples in many CF subjects. The presence of an oral-like lower airways
microbiome correlated with a significant increase in bacterial density and
inflammation. These early changes occurred in many patients, despite the use of
antibiotic prophylaxis in our cohort during the first two years of life. The
majority of CF subjects older than four harbored a pathogen dominated airway
microbiome, which was associated with a further increase in inflammation and the
onset of structural lung disease, despite a negligible increase in bacterial
density compared to younger patients with an oral-like airway microbiome. Our
findings suggest that changes within the CF lower airways microbiome occur during
the first years of life and that distinct microbial signatures are associated
with the progression of early CF lung disease.
PMID- 29346421
TI - The absence of specific yeast heat-shock proteins leads to abnormal aggregation
and compromised autophagic clearance of mutant Huntingtin proteins.
AB - The functionality of a protein depends on its correct folding, but newly
synthesized proteins are susceptible to aberrant folding and aggregation. Heat
shock proteins (HSPs) function as molecular chaperones that aid in protein
folding and the degradation of misfolded proteins. Trinucleotide (CAG) repeat
expansion in the Huntingtin gene (HTT) results in the expression of misfolded
Huntingtin protein (Htt), which contributes to the development of Huntington's
disease. We previously found that the degradation of mutated Htt with polyQ
expansion (Htt103QP) depends on both ubiquitin proteasome system and autophagy.
However, the role of heat shock proteins in the clearance of mutated Htt remains
poorly understood. Here, we report that cytosolic Hsp70 (Ssa family), its
nucleotide exchange factors (Sse1 and Fes1), and a Hsp40 co-chaperone (Ydj1) are
required for inclusion body formation of Htt103QP proteins and their clearance
via autophagy. Extended induction of Htt103QP-GFP leads to the formation of a
single inclusion body in wild-type yeast cells, but mutant cells lacking these
HSPs exhibit increased number of Htt103QP aggregates. Most notably, we detected
more aggregated forms of Htt103QP in sse1Delta mutant cells using an agarose gel
assay. Increased protein aggregates are also observed in these HSP mutants even
in the absence Htt103QP overexpression. Importantly, these HSPs are required for
autophagy-mediated Htt103QP clearance, but are less critical for proteasome
dependent degradation. These findings suggest a chaperone network that
facilitates inclusion body formation of misfolded proteins and the subsequent
autophagic clearance.
PMID- 29346422
TI - Nanoparticle effect on neutrophil produced myeloperoxidase.
AB - Nanoparticles affect the immune system as they may interact directly with immune
cells and activate them. However, it is possible that nanoparticles also interact
with released cytokines and immunologically active enzymes. To test this
hypothesis, the activity of myeloperoxidase released from activated neutrophils
was measured in the presence of nanoparticles with different chemistry and size.
In high concentrations of nanoparticles, myeloperoxidase activity is decreased
whereas in low concentrations of nanoparticles the activity is increased. The
effect of the nanoparticles on myeloperoxidase is dependent on the total protein
concentration as low concentrations of bovine serum albumin together with
nanoparticles further increase the myeloperoxidase activity. The results herein
show that nanoparticles affect the immune response not only at the cellular level
but also on released immune effectors. In particular, they show that the
nanoparticle effect on myeloperoxidase activity in the neutrophil degranulation
environment is the result of an intricate interplay between the enzyme and
protein concentrations in the environment and the available surface area on the
nanoparticle.
PMID- 29346423
TI - The association of estimated salt intake with blood pressure in a Viet Nam
national survey.
AB - OBJECTIVE: To evaluate the association of salt consumption with blood pressure in
Viet Nam, a developing country with a high level of salt consumption. DESIGN AND
SETTING: Analysis of a nationally representative sample of Vietnamese adults 25
65 years of age who were surveyed using the World Health Organization STEPwise
approach to Surveillance protocol. Participants who reported acute illness,
pregnancy, or current use of antihypertensive medications were excluded. Daily
salt consumption was estimated from fasting mid-morning spot urine samples.
Associations of salt consumption with systolic blood pressure and prevalent
hypertension were assessed using adjusted linear and generalized linear models.
Interaction terms were tested to assess differences by age, smoking, alcohol
consumption, and rural/urban status. RESULTS: The analysis included 2,333
participants (mean age: 37 years, 46% male, 33% urban). The average estimated
salt consumption was 10g/day. No associations of salt consumption with blood
pressure or prevalent hypertension were observed at a national scale in men or
women. The associations did not differ in subgroups defined by age, smoking, or
alcohol consumption; however, associations differed between urban and rural
participants (p-value for interaction of urban/rural status with salt
consumption, p = 0.02), suggesting that higher salt consumption may be associated
with higher systolic blood pressure in urban residents but lower systolic blood
pressure in rural residents. CONCLUSIONS: Although there was no evidence of an
association at a national level, associations of salt consumption with blood
pressure differed between urban and rural residents in Viet Nam. The reasons for
this differential association are not clear, and given the large rate of rural to
urban migration experienced in Viet Nam, this topic warrants further
investigation.
PMID- 29346424
TI - Higher sequence diversity in the vaginal tract than in blood at early HIV-1
infection.
AB - In the majority of cases, human immunodeficiency virus type 1 (HIV-1) infection
is transmitted through sexual intercourse. A single founder virus in the blood of
the newly infected donor emerges from a genetic bottleneck, while in rarer
instances multiple viruses are responsible for systemic infection. We sought to
characterize the sequence diversity at early infection, between two distinct
anatomical sites; the female reproductive tract vs. systemic compartment. We
recruited 72 women from Uganda and Zimbabwe within seven months of HIV-1
infection. Using next generation deep sequencing, we analyzed the total genetic
diversity within the C2-V3-C3 envelope region of HIV-1 isolated from the female
genital tract at early infection and compared this to the diversity of HIV-1 in
plasma. We then compared intra-patient viral diversity in matched cervical and
blood samples with three or seven months post infection. Genetic analysis of the
C2-V3-C3 region of HIV-1 env revealed that early HIV-1 isolates within blood
displayed a more homogeneous genotype (mean 1.67 clones, range 1-5 clones) than
clones in the female genital tract (mean 5.7 clones, range 3-10 clones)
(p<0.0001). The higher env diversity observed within the genital tract compared
to plasma was independent of HIV-1 subtype (A, C and D). Our analysis of early
mucosal infections in women revealed high HIV-1 diversity in the vaginal tract
but few transmitted clones in the blood. These novel in vivo finding suggest a
possible mucosal sieve effect, leading to the establishment of a homogenous
systemic infection.
PMID- 29346425
TI - Hippocampal corticotropin-releasing hormone neurons support recognition memory
and modulate hippocampal excitability.
AB - Corticotropin-releasing hormone (CRH) signaling in the hippocampus has been
established to be important for mediating the effects of stress on learning and
memory. Given our laboratory's recent characterization of a subset of hippocampal
CRH neurons as a novel class of GABAergic interneurons, we hypothesized that
these local GABAergic hippocampal CRH neurons may influence hippocampal function.
Here we applied an array of molecular tools to selectively label and manipulate
hippocampal CRH neurons in mice, in order to assess this interneuron population's
impact on hippocampus-dependent behaviors and hippocampal network excitability.
Genetically-targeted ablation of hippocampal CRH neurons in vivo impaired object
recognition memory and substantially enhanced the severity of kainic acid-induced
seizures. Conversely, selective activation of CRH neurons in vitro suppressed the
excitability of the mossy fiber-CA3 pathway. Additional experiments are needed to
reconcile the functions of GABA and CRH signaling of hippocampal CRH neurons on
hippocampal function. However, our results indicate that this interneuron
population plays an important role in maintaining adaptive network excitability,
and provide a specific circuit-level mechanism for this role.
PMID- 29346428
TI - Revisiting facial resemblance in couples.
AB - It is widely believed that couples look alike. Consistently, previous research
reported higher facial similarity for couples than non-couples, and that facial
similarity predicts marital satisfaction. However, it is unclear if facial
similarity in couples shown in previous studies was solely driven by extrinsic
features like hairstyle, glasses, etc. Also unclear is what attributes are
perceived as similar from the faces of a couple. In three experiments, we showed
that faces were considered more similar in couples than non-couples even without
extrinsic features. Personality and age perceived from faces were also more
similar in couples. Importantly, by matching pairs of faces according to their
perceived personality, we found that a higher similarity in the perceived
personality of a face pair led to higher facial similarity and couple likelihood
ratings. These findings suggest that, instead of a result of pure physical
analyses, facial similarity in couples is partly based on active social cognitive
judgments on perceived personality, which may reveal the actual personality of
the couples and thus inform relationship quality.
PMID- 29346427
TI - Soluble factors from adipose tissue-derived mesenchymal stem cells promote canine
hepatocellular carcinoma cell proliferation and invasion.
AB - The potential effects of adipose tissue-derived mesenchymal stem cells (AT-MSCs)
on the growth and invasion of canine tumours including hepatocellular carcinoma
(HCC) are not yet understood. Moreover in humans, the functional contribution of
AT-MSCs to malignancies remains controversial. The purpose of this study was to
investigate the effects of AT-MSCs on the proliferation and invasion of canine
HCC cells in vitro. The effect of AT-MSCs on mRNA levels of factors related to
HCC progression were also evaluated. Conditioned medium from AT-MSCs (AT-MSC-CM)
significantly enhanced canine HCC cell proliferation and invasion. Moreover, mRNA
expression levels of transforming growth factor-beta 1, epidermal growth factor
A, hepatocyte growth factor, platelet-derived growth factor-beta, vascular
endothelial growth factor, and insulin-like growth factor 2 were 2.3 +/- 0.4, 2.0
+/- 0.5, 5.7 +/- 1.9, 1.7 +/- 0.2, 2.1 +/- 0.4, and 1.4 +/- 0.3 times higher,
respectively (P < 0.05). The mRNA expression level of MMP-2 also increased (to
4.0 +/- 1.2 times control levels) in canine HCC cells co-cultured with AT-MSCs,
but MMP-9 mRNA significantly decreased (to 0.5 +/- 0.1 times control levels).
These findings suggest that soluble factors from AT-MSCs promote the
proliferation and invasion of canine HCC cells.
PMID- 29346426
TI - Proliferation and survival of human amniotic epithelial cells during their
hepatic differentiation.
AB - Stem cells derived from placental tissues are an attractive source of cells for
regenerative medicine. Amniotic epithelial cells isolated from human amnion
(hAECs) have desirable and competitive characteristics that make them stand out
between other stem cells. They have the ability to differentiate toward all three
germ layers, they are not tumorigenic and they have immunosuppressive properties.
Although liver transplantation is the best way to treat acute and chronic hepatic
failure patients, there are several obstacles. Recently, stem cells have been
spotlighted as alternative source of hepatocytes because of their potential for
hepatogenic differentiation. In this work, we aimed to study the proliferation
and survival of the hAECs during their hepatic differentiation. We have also
analyzed the changes in pluripotency and hepatic markers. We differentiated
amniotic cells applying a specific hepatic differentiation (HD) protocol. We
determined by qRT-PCR that hAECs express significant levels of SOX-2, OCT-4 and
NANOG during at least 15 days in culture and these pluripotent markers diminish
during HD. SSEA-4 expression was reduced during HD, measured by
immunofluorescence. Morphological characteristics became more similar to hepatic
ones in differentiated cells and representative hepatic markers significantly
augmented their expression, measured by qRT-PCR and Western blot. Cells achieved
a differentiation efficiency of 75%. We observed that HD induced proliferation
and promoted survival of hAECs, during 30 days in culture, evaluated by 3H
thymidine incorporation and MTT assay. HD also promoted changes in hAECs cell
cycle. Cyclin D1 expression increased, while p21 and p53 levels were reduced.
Immunofluorescence analysis showed that Ki-67 expression was upregulated during
HD. Finally, ERK 1/2 phosphorylation, which is intimately linked to proliferation
and cell survival, augmented during all HD process and the inhibition of this
signaling pathway affected not only proliferation but also differentiation. Our
results suggest that HD promotes proliferation and survival of hAECs, providing
important evidence about the mechanisms governing their hepatic differentiation.
We bring new knowledge concerning some of the optimal transplantation conditions
for these hepatic like cells.
PMID- 29346429
TI - The farnesoid X receptor agonist obeticholic acid upregulates biliary excretion
of asymmetric dimethylarginine via MATE-1 during hepatic ischemia/reperfusion
injury.
AB - BACKGROUND: We previously showed that increased asymmetric dimethylarginine
(ADMA) biliary excretion occurs during hepatic ischemia/reperfusion (I/R),
prompting us to study the effects of the farnesoid X receptor (FXR) agonist
obeticholic acid (OCA) on bile, serum and tissue levels of ADMA after I/R.
MATERIAL AND METHODS: Male Wistar rats were orally administered 10mg/kg/day of
OCA or vehicle for 5 days and were subjected to 60 min partial hepatic ischemia
or sham-operated. After a 60 min reperfusion, serum, tissue and bile ADMA levels,
liver mRNA and protein expression of ADMA transporters (CAT-1, CAT-2A, CAT-2B,
OCT-1, MATE-1), and enzymes involved in ADMA synthesis (protein-arginine-N
methyltransferase-1, PRMT-1) and metabolism (dimethylarginine
dimethylaminohydrolase-1, DDAH-1) were measured. RESULTS: OCA administration
induced a further increase in biliary ADMA levels both in sham and I/R groups,
with no significant changes in hepatic ADMA content. A reduction in CAT-1, CAT-2A
or CAT-2B transcripts was found in OCA-treated sham-operated rats compared with
vehicle. Conversely, OCA administration did not change CAT-1, CAT-2A or CAT-2B
expression, already reduced by I/R. However, a marked decrease in OCT-1 and
increase in MATE-1 expression was observed. A similar trend occurred with protein
expression. CONCLUSION: The reduced mRNA expression of hepatic CAT transporters
suggests that the increase in serum ADMA levels is probably due to decreased
liver uptake of ADMA from the systemic circulation. Conversely, the mechanism
involved in further increasing biliary ADMA levels in sham and I/R groups treated
with OCA appears to be MATE-1-dependent.
PMID- 29346430
TI - Estimation of inhalation flow profile using audio-based methods to assess inhaler
medication adherence.
AB - Asthma and chronic obstructive pulmonary disease (COPD) patients are required to
inhale forcefully and deeply to receive medication when using a dry powder
inhaler (DPI). There is a clinical need to objectively monitor the inhalation
flow profile of DPIs in order to remotely monitor patient inhalation technique.
Audio-based methods have been previously employed to accurately estimate flow
parameters such as the peak inspiratory flow rate of inhalations, however, these
methods required multiple calibration inhalation audio recordings. In this study,
an audio-based method is presented that accurately estimates inhalation flow
profile using only one calibration inhalation audio recording. Twenty healthy
participants were asked to perform 15 inhalations through a placebo ElliptaTM DPI
at a range of inspiratory flow rates. Inhalation flow signals were recorded using
a pneumotachograph spirometer while inhalation audio signals were recorded
simultaneously using the Inhaler Compliance Assessment device attached to the
inhaler. The acoustic (amplitude) envelope was estimated from each inhalation
audio signal. Using only one recording, linear and power law regression models
were employed to determine which model best described the relationship between
the inhalation acoustic envelope and flow signal. Each model was then employed to
estimate the flow signals of the remaining 14 inhalation audio recordings. This
process repeated until each of the 15 recordings were employed to calibrate
single models while testing on the remaining 14 recordings. It was observed that
power law models generated the highest average flow estimation accuracy across
all participants (90.89+/-0.9% for power law models and 76.63+/-2.38% for linear
models). The method also generated sufficient accuracy in estimating inhalation
parameters such as peak inspiratory flow rate and inspiratory capacity within the
presence of noise. Estimating inhaler inhalation flow profiles using audio based
methods may be clinically beneficial for inhaler technique training and the
remote monitoring of patient adherence.
PMID- 29346431
TI - Sensitivity and specificity of two dried blood spot methods for HIV-1 viral load
monitoring among patients in Hanoi, Vietnam.
AB - The use of dried blood spot (DBS) specimens for HIV viral load (VL) monitoring is
recommended to support the roll-out of routine VL monitoring in low and middle
income countries (LMICs). To better understand the use of DBS for VL monitoring,
we evaluated two DBS testing methods, Roche TaqMan(r) Free Virus Evolution
protocol (DBS-FVE) and Roche TaqMan(r) SPEX protocol (DBS-SPEX)) in patients
receiving ART at an HIV clinic in Hanoi, Vietnam. Sensitivity, specificity,
positive predictive value (PPV), and negative predictive value (NPV) were
calculated for each DBS testing method at the thresholds of 1000 and 5000
copies/ml compared to plasma VL. At a threshold of 1000 copies/ml, sensitivity,
specificity, PPV and NPV of the DBS-SPEX method were 98.8% (95% CI: 93.3%-100%),
74.3% (95% CI: 70.8%-77.5%), 31.5% (95% CI: 25.8%-37.6%), and 99.8% (95% CI:
98.9%-100%), respectively. Increasing the VL threshold value to 5000 copies/ml
improved specificity (97.9% CI: 96.6%-98.9%) and PPV (83.9% CI: 74.5%-90.9%).
Using the DBS-FVE method, at the threshold of 1000 copies/ml and with a
correction factor of +0.3 log copies/ml, sensitivity was 95.1% (87.8%-98.6%) and
specificity was 98.8% (97.7%-99.5%). Sensitivity decreased at the threshold of
5000 copies/ml (65.8%, 95% CI: 54.3%-76.1%). With a correction factor of +0.7 log
copies/ml, the sensitivity was 96.3% (89.6%-99.2%) and specificity was 98.2%
(96.9%-99.1%) at the threshold of 1000 copies/ml. We found that the Roche DBS-FVE
method, with a +0.7 log copies/ml correction factor, performed well with
sensitivity and specificity greater than 96% at a VL threshold of 1000 copies/m.
These findings add to the growing body of evidence supporting the use of DBS VL
testing for ART monitoring. Future research should evaluate the association
between VL results by DBS and clinical outcome measures such as HIV drug
resistance, morbidity, and mortality.
PMID- 29346432
TI - Retraction: Virulent Diuraphis noxia Aphids Over-Express Calcium Signaling
Proteins to Overcome Defenses of Aphid-Resistant Wheat Plants.
PMID- 29346433
TI - Vault RNAs partially induces drug resistance of human tumor cells MCF-7 by
binding to the RNA/DNA-binding protein PSF and inducing oncogene GAGE6.
AB - BACKGROUND: Vault is the largest nonicosahedral cytosolic nucleoprotein particle,
which is widely involved in induction of chemoresistance and lead to failure in
long-term chemotherapy. Vault contains three different major vault proteins
(MVPs) and four vault RNAs paralogues (vtRNAs, vtRNA1-1, vtRNA1-2, vtRNA1-3 and
vtRNA2-1). Disruption of the MVPs do not induce hypersensitivity while expression
of vtRNAs contributes to cells' drug resistance, indicates that vtRNAs, but not
MVPs play an important role in causing drug resistance. Polypyrimidine tract
binding protein associated splicing factor (PSF) contributes to cell sensitivity
to chemotherapy by its transcriptional activity, promotes us to figure out its
potential association with vtRNAs. METHODS: We investigate the interaction
between PSF and vtRNAs by electrophoretic mobility shift assays (EMSA) and RNA
immunoprecipitation (IP), and showed the binding between PSF and vtRNAs.
Chromatin Immunoprecipitation (ChIP) was performed to detect the effects of
vtRNAs on the interaction of PSF with GAGE6 promoter. The role of vtRNAs on
chemoresistance in MCF-7 was detected by CCK-8 and EdU staining. The independent
role of vtRNAs with MVP is detected by MVP or vtRNAs knockdown. RESULTS: The
complex with vtRNA1-1 releases PSF, allowing transcription of GAGE6 to proceed.
Then we showed that induction of GAGE6 caused drug resistance by promoting cell
proliferation and colony formation in soft agar. Ectopic expression of shRNA
targets to vtRNA1-1 further confirmed the role of vtRNA1-1 in regulating PSF
transcriptional activity independent with the expression of MVP. By vtRNA1-1 or
MVP knockdown, it is revealed that vtRNA1-1 caused chemoresistance independent of
MVP. Furthermore, knockdown of GAGE6 does not cause drug resistance, indicates
the GAGE6 is directly involved in cell proliferation, but not the drug
resistance. CONCLUSION: These results suggest that vtRNAs regulates cell
proliferation, drug resistance, and possibly other physiological processes of
humans, by complex formation with PSF.
PMID- 29346434
TI - Cognitive distortions and gambling near-misses in Internet Gaming Disorder: A
preliminary study.
AB - Increased cognitive distortions (i.e. biased processing of chance, probability
and skill) are a key psychopathological process in disordered gambling. The
present study investigated state and trait aspects of cognitive distortions in 22
individuals with Internet Gaming Disorder (IGD) and 22 healthy controls.
Participants completed the Gambling Related Cognitions Scale as a trait measure
of cognitive distortions, and played a slot machine task delivering wins, near
misses and full-misses. Ratings of pleasure ("liking") and motivation to play
("wanting") were taken following the different outcomes, and gambling persistence
was measured after a mandatory phase. IGD was associated with elevated trait
cognitive distortions, in particular skill-oriented cognitions. On the slot
machine task, the IGD group showed increased "wanting" ratings compared with
control participants, while the two groups did not differ regarding their
"liking" of the game. The IGD group displayed increased persistence on the slot
machine task. Near-miss outcomes did not elicit stronger motivation to play
compared to full-miss outcomes overall, and there was no group difference on this
measure. However, a near-miss position effect was observed, such that near-misses
stopping before the payline were rated as more motivating than near-misses that
stopped after the payline, and this differentiation was attenuated in the IGD
group, suggesting possible counterfactual thinking deficits in this group. These
data provide preliminary evidence for increased incentive motivation and
cognitive distortions in IGD, at least in the context of a chance-based gambling
environment.
PMID- 29346435
TI - Influenza A virus hemagglutinin glycosylation compensates for antibody escape
fitness costs.
AB - Rapid antigenic evolution enables the persistence of seasonal influenza A and B
viruses in human populations despite widespread herd immunity. Understanding
viral mechanisms that enable antigenic evolution is critical for designing
durable vaccines and therapeutics. Here, we utilize the primerID method of error
correcting viral population sequencing to reveal an unexpected role for
hemagglutinin (HA) glycosylation in compensating for fitness defects resulting
from escape from anti-HA neutralizing antibodies. Antibody-free propagation
following antigenic escape rapidly selected viruses with mutations that modulated
receptor binding avidity through the addition of N-linked glycans to the HA
globular domain. These findings expand our understanding of the viral mechanisms
that maintain fitness during antigenic evolution to include glycan addition, and
highlight the immense power of high-definition virus population sequencing to
reveal novel viral adaptive mechanisms.
PMID- 29346436
TI - Bone marrow concentrate promotes bone regeneration with a suboptimal-dose of
rhBMP-2.
AB - Bone marrow concentrate (BMC), which is enriched in mononuclear cells (MNCs) and
platelets, has recently attracted the attention of clinicians as a new optional
means for bone engineering. We previously reported that the osteoinductive effect
of bone morphogenetic protein-2 (BMP-2) could be enhanced synergistically by co
transplantation of peripheral blood (PB)-derived platelet-rich plasma (PRP). This
study aims to investigate whether BMC can effectively promote bone formation
induced by low-dose BMP-2, thereby reducing the undesirable side-effects of BMP
2, compared to PRP. Human BMC was obtained from bone marrow aspirates using an
automated blood separator. The BMC was then seeded onto beta-TCP granules pre
adsorbed with a suboptimal-dose (minimum concentration to induce bone formation
at 2 weeks in mice) of recombinant human (rh) BMP-2. These specimens were
transplanted subcutaneously to the dorsal skin of immunodeficient-mice and the
induction of ectopic bone formation was assessed 2 and 4 weeks post
transplantation. Transplantations of five other groups [PB, PRP, platelet-poor
plasma (PPP), bone marrow aspirate (BM), and BM-PPP] were employed as
experimental controls. Then, to clarify the effects on vertical bone
augmentation, specimens from the six groups were transplanted for on-lay
placement on the craniums of mice. The results indicated that BMC, which
contained an approximately 2.5-fold increase in the number of MNCs compared to
PRP, could accelerate ectopic bone formation until 2 weeks post-transplantation.
On the cranium, the BMC group promoted bone augmentation with a suboptimal-dose
of rhBMP-2 compared to other groups. Particularly in the BMC specimens harvested
at 4 weeks, we observed newly formed bone surrounding the TCP granules at sites
far from the calvarial bone. In conclusion, the addition of BMC could reduce the
amount of rhBMP-2 by one-half via its synergistic effect on early-phase
osteoinduction. We propose here that BMC transplantation facilitates the clinical
use of rhBMP-2 as an alternative strategy for bone engineering.
PMID- 29346437
TI - Tissue-specific transcriptome analyses provide new insights into GPCR signalling
in adult Schistosoma mansoni.
AB - Schistosomes are blood-dwelling trematodes with global impact on human and animal
health. Because medical treatment is currently based on a single drug,
praziquantel, there is urgent need for the development of alternative control
strategies. The Schistosoma mansoni genome project provides a platform to study
and connect the genetic repertoire of schistosomes to specific biological
functions essential for successful parasitism. G protein-coupled receptors
(GPCRs) form the largest superfamily of transmembrane receptors throughout the
Eumetazoan phyla, including platyhelminths. Due to their involvement in diverse
biological processes, their pharmacological importance, and proven druggability,
GPCRs are promising targets for new anthelmintics. However, to identify candidate
receptors, a more detailed understanding of the roles of GPCR signalling in
schistosome biology is essential. An updated phylogenetic analysis of the S.
mansoni GPCR genome (GPCRome) is presented, facilitated by updated genome data
that allowed a more precise annotation of GPCRs. Additionally, we review the
current knowledge on GPCR signalling in this parasite and provide new insights
into the potential roles of GPCRs in schistosome reproduction based on the
findings of a recent tissue-specific transcriptomic study in paired and unpaired
S. mansoni. According to the current analysis, GPCRs contribute to gonad-specific
functions but also to nongonad, pairing-dependent processes. The latter may
regulate gonad-unrelated functions during the multifaceted male-female
interaction. Finally, we compare the schistosome GPCRome to that of another
parasitic trematode, Fasciola, and discuss the importance of GPCRs to basic and
applied research. Phylogenetic analyses display GPCR diversity in free-living and
parasitic platyhelminths and suggest diverse functions in schistosomes. Although
their roles need to be substantiated by functional studies in the future, the
data support the selection of GPCR candidates for basic and applied studies,
invigorating the exploitation of this important receptor class for drug discovery
against schistosomes but also other trematodes.
PMID- 29346438
TI - Colonization of the cervicovaginal space with Gardnerella vaginalis leads to
local inflammation and cervical remodeling in pregnant mice.
AB - The role of the cervicovaginal (CV) microbiome in regulating cervical function
during pregnancy is poorly understood. Gardnerella vaginalis (G. vaginalis) is
the most common bacteria associated with the diagnosis of bacterial vaginosis
(BV). While BV has been associated with preterm birth (PTB), clinical trials
targeting BV do not decrease PTB rates. It remains unknown if G. vaginalis is
capable of triggering molecular, biomechanical and cellular events that could
lead to PTB. The objective of this study was to determine if cervicovaginal
colonization with G. vaginalis, in pregnant mice, induced cervical remodeling and
modified cervical function. CD-1 timed-pregnant mice received a 5X108 CFU/mL
intravaginal inoculation of G. vaginalis or control on embryonic day 12 (E12) and
E13. On E15, the mice were sacrificed and cervicovaginal fluid (CVF), amniotic
fluid (AF), cervix, uterus, placentas and fetal membranes (FM) were collected.
Genomic DNA was isolated from the CVF, placenta, uterus and FM and QPCR was
performed to confirm colonization. IL-6 was measured in the CVF and AF and
soluble e-cadherin (seCAD) was assessed in the CVF by ELISA. RNA was extracted
from the cervices to evaluate IL-10, IL-8, IL-1beta, TNF-alpha, Tff-1, SPINK-5,
HAS-1 and LOX expression via QPCR. Mucicarmine and trichrome staining was used to
assess cervical mucin and collagen. Biomechanical properties of the cervix were
studied using quasi-static tensile load-to-failure biomechanical tests. G.
vaginalis successfully colonized the CV space. This colonization induced immune
responses (increased IL-6 levels in CVF and AF, increased mRNA expression of
cervical cytokines), altered the epithelial barrier (increased seCAD in the CVF),
induced cervical remodeling (increased mucin production, altered collagen) and
altered cervical biomechanical properties (a decrease in biomechanical modulus
and an increase in maximum strain). The ability of G. vaginalis to induce these
molecular, immune, cellular and biomechanical changes suggests that this
bacterium may play a pathogenic role in premature cervical remodeling leading to
PTB.
PMID- 29346439
TI - Interspecies diversity of chloride channel regulators, calcium-activated 3 genes.
AB - Members of the chloride channel regulators, calcium-activated (CLCA) family, have
been implicated in diverse biomedical conditions, including chronic inflammatory
airway diseases such as asthma, chronic obstructive pulmonary disease, and cystic
fibrosis, the activation of macrophages, and the growth and metastatic spread of
tumor cells. Several observations, however, could not be repeated across species
boundaries and increasing evidence suggests that select CLCA genes are
particularly prone to dynamic species-specific evolvements. Here, we
systematically characterized structural and expressional differences of the CLCA3
gene across mammalian species, revealing a spectrum of gene duplications, e.g.,
in mice and cows, and of gene silencing via diverse chromosomal modifications in
pigs and many primates, including humans. In contrast, expression of a canonical
CLCA3 protein from a single functional gene seems to be evolutionarily retained
in carnivores, rabbits, guinea pigs, and horses. As an accepted asthma model, we
chose the cat to establish the tissue and cellular expression pattern of the
CLCA3 protein which was primarily found in mucin-producing cells of the
respiratory tract and in stratified epithelia of the esophagus. Our results
suggest that, among developmental differences in other CLCA genes, the CLCA3 gene
possesses a particularly high dynamic evolutionary diversity with pivotal
consequences for humans and other primates that seem to lack a CLCA3 protein. Our
data also help to explain previous contradictory results on CLCA3 obtained from
different species and warrant caution in extrapolating data from animal models in
conditions where CLCA3 may be involved.
PMID- 29346440
TI - Geographical distribution of soil transmitted helminths and the effects of
community type in South Asia and South East Asia - A systematic review.
AB - BACKGROUND: Soil-transmitted helminth (STH) infections are among the most
prevalent neglected tropical diseases (NTD) worldwide. Since the publication of
the WHO road map to combat NTD in 2012, there has been a renewed commitment to
control STH. In this study, we analysed the geographical distribution and effect
of community type on prevalence of hookworm, Trichuris and Ascaris in south Asia
and south east Asia. METHODOLOGY: We conducted a systematic review of open-access
literature published in PubMed Central and the Global Atlas of Helminth
Infection. A total of 4182 articles were available and after applying selection
criteria, 174 studies from the region were retained for analysis. PRINCIPAL
FINDINGS: Ascaris was the commonest STH identified with an overall prevalence of
18% (95% CI, 14-23%) followed by Trichuris (14%, 9-19%) and hookworm (12%, 9
15%). Hookworm prevalence was highest in Laos, Vietnam and Cambodia. We found a
geographical overlap in countries with high prevalence rates for Trichuris and
Ascaris (Malaysia, Philippines, Myanmar, Vietnam and Bangladesh). When the effect
of community type was examined, prevalence rates of hookworm was comparable in
rural (19%, 14-24%) and tribal communities (14%, 10-19%). Tribal communities,
however, showed higher prevalence of Trichuris (38%, 18-63%) and Ascaris (32%, 23
43%) than rural communities (13%, 9-20% and 14%, 9-20% respectively).
Considerable between and within country heterogeneity in the distribution of STH
(I2 >90%) was also noted. When available data from school aged children (SAC)
were analysed, prevalence of Ascaris (25% 16-31%) and Trichuris (22%, 14-34%)
were higher than among the general population while that of hookworm (10%, 7-16%)
was comparable. CONCLUSIONS/SIGNIFICANCE: Our analysis showed significant
variation in prevalence rates between and within countries in the region.
Highlighting the importance of community type in prevalence and species mix, we
showed that tribal and rural communities had higher hookworm infections than
urban communities and for ascariasis and trichuriasis, tribal populations had
higher levels of infection than rural populations. We also found a higher
prevalence of ascariasis and trichuriasis in SAC compared to the general
population but comparable levels of hookworm infections. These key findings need
to be taken into account in planning future MDA and other interventions.
PMID- 29346441
TI - A portable system for processing donated whole blood into high quality components
without centrifugation.
AB - BACKGROUND: The use of centrifugation-based approaches for processing donated
blood into components is routine in the industrialized world, as disparate
storage conditions require the rapid separation of 'whole blood' into distinct
red blood cell (RBC), platelet, and plasma products. However, the logistical
complications and potential cellular damage associated with
centrifugation/apheresis manufacturing of blood products are well documented. The
objective of this study was to evaluate a proof-of-concept system for whole blood
processing, which does not employ electromechanical parts, is easily portable,
and can be operated immediately after donation with minimal human labor. METHODS
AND FINDINGS: In a split-unit study (n = 6), full (~500mL) units of freshly
donated whole blood were divided, with one half processed by conventional
centrifugation techniques and the other with the new blood separation system.
Each of these processes took 2-3 hours to complete and were performed in
parallel. Blood products generated by the two approaches were compared using an
extensive panel of cellular and plasma quality metrics. Comparison of nearly all
RBC parameters showed no significant differences between the two approaches,
although the portable system generated RBC units with a slight but statistically
significant improvement in 2,3-diphosphoglyceric acid concentration (p < 0.05).
More notably, several markers of platelet damage were significantly and
meaningfully higher in products generated with conventional centrifugation: the
increase in platelet activation (assessed via P-selectin expression in platelets
before and after blood processing) was nearly 4-fold higher for platelet units
produced via centrifugation, and the release of pro-inflammatory mediators
(soluble CD40-ligand, thromboxane B2) was significantly higher for centrifuged
platelets as well (p < 0.01). CONCLUSION: This study demonstrated that a simple,
passive system for separating donated blood into components may be a viable
alternative to centrifugation-particularly for applications in remote or resource
limited settings, or for patients requiring highly functional platelet product.
PMID- 29346442
TI - Comparative metabolic ecology of tropical herbivorous echinoids on a coral reef.
AB - BACKGROUND: The metabolic rate of consumers is a key driver of ecosystem
dynamics. On coral reefs, herbivorous echinoids consume fleshy algae,
facilitating the growth of reef-building calcified organisms; however, little is
known about differences among species in their metabolic and functional ecology.
Here, we used log-linear (log-log) regression models to examine the allometric
scaling of mass and routine metabolic rate for five common herbivorous echinoids
on a Hawaiian coral reef: Echinothrix calamaris, E. diadema, Echinometra
matthaei, Heterocentrotus mammillatus, and Tripneustes gratilla. Scaling
relationships were then contrasted with empirical observations of echinoid
ecology and general metabolic theory to broaden our understanding of diversity in
the metabolic and functional ecology of tropical herbivorous echinoids. RESULTS:
Test diameter and species explained 98% of the variation in mass, and mass and
species explained 92.4% and 87.5% of the variation in individual (I) and mass
specific (B) metabolic rates, respectively. Scaling exponents did not differ for
mass or metabolism; however, normalizing constants differed significantly among
species. Mass varied as the cube of test diameter (b = 2.9), with HM exhibiting a
significantly higher normalizing constant than other species, likely due to its
heavily-calcified spines and skeleton. Individual metabolic rate varied
approximately as the 2/5 power of mass (gamma = 0.44); significantly smaller than
the 3/4 universal scaling coefficient, but inclusive of 2/3 scaling. E. calamaris
and H. mammillatus exhibited the lowest normalizing constants, corresponding with
their slow-moving, cryptic, rock-boring life-history. In contrast, E. calamaris,
E. diadema, and T. gratilla, exhibited higher metabolic rates, likely reflecting
their higher levels of activity and ability to freely browse for preferred algae
due to chemical anti-predator defenses. Thus, differences in metabolic scaling
appeared to correspond with differences in phylogeny, behavior, and ecological
function. Such comparative metabolic assessments are central to informing theory,
ecological models, and the effective management of ecosystems.
PMID- 29346443
TI - Exposure to previous cART is associated with significant liver fibrosis and
cirrhosis in human immunodeficiency virus-infected patients.
AB - INTRODUCTION: Combined antiretroviral therapy (cART) has improved survival in HIV
patients. While the first antiretrovirals, which became available in particular D
drugs (especially didanosine and stavudine) and unboosted protease inhibitors,
may impair liver function, the modern cART seems to decrease liver fibrosis. This
study assessed the influence of exposure to previous antiretrovirals on liver
fibrosis in HIV-infected patients. METHODS: This observational cross-sectional
single-center study recruited 333 HIV patients and assessed liver fibrosis using
transient elastography (TE). RESULTS: 83% were male with a median age of 45,
while 131 were co-infected with viral hepatitis. Overall, 18% had significant
fibrosis and 7.5% had cirrhosis. 11% of HIV mono-infected patients had
significant fibrosis and 2% had cirrhosis. HCV infection (OR:5.3), history of
exposure to didanosine (OR:2.7) and HIV load below 40copies/mL (OR:0.5) were
independently associated with significant fibrosis, while HCV (OR:5.8), exposure
to didanosine (OR:2.9) and azidothymidine (OR:2.8) were independently associated
with cirrhosis. Interestingly, in HIV mono-infected patients, a HIV-load below
40copies/mL (OR:0.4) was independently associated with significant fibrosis, and
didanosine (OR:20.8) with cirrhosis. CONCLUSION: In conclusion, history of
exposure to didanosine and azidothymidine continues to have an impact on the
presence of liver cirrhosis in HIV patients. However, HCV co-infection and
ongoing HIV-replication have the strongest effect on development of significant
fibrosis in these patients.
PMID- 29346444
TI - Social and structural barriers for adherence to methadone maintenance treatment
among Vietnamese opioid dependence patients.
AB - INTRODUCTION: Methadone maintenance treatment (MMT) services may reduce the risk
of HIV transmission if patients completely adhere to the treatment. Identifying
adherence patterns and potential related factors is vital for the sustainability
of MMT program in Vietnam. This study examined social and structural factors
associated with adherence to MMT among patients in different service delivery
models. MATERIALS AND METHODS: A total of 510 patients at three MMT clinics in
Hanoi were interviewed. Measures of self-reported adherence included the number
of missed doses in the past 7 days and the level of adherence in the past 30 days
using a visual analog scale (VAS) scoring from 0 (non-adherence) to 100 (perfect
adherence). Multivariate regressions were employed to identify factors associated
with non-adherence to MMT. RESULTS: A total of 17.7% of participants reported
incomplete MMT adherence in the last 30 days and 8.3% reported missing a dose in
the last seven days, respectively. Living with HIV/AIDS, poor self-care and usual
activities, and disclosure of health issues to spouses or intimate partners were
associated with non-adherence. Those patients with pain or depression were more
likely to report better adherence. Disclosing health status to spouse/partner
increased the risk of incomplete adherence, while disclosing to friends reduced
the number of missed dose in the last seven days. Patients attending clinics with
comprehensive services had a lower VAS score of adherence compared to those
enrolling in clinics with only MMT and general health care. CONCLUSIONS:
Sustaining the compliance of patients to MMT is principal in the rapid expansion
of this service in Vietnam. It is necessary to address the complexity of health
care demands of drug users, their difficulties to be rehabilitated into workforce
and society, and the stigmatization to maximize the outcomes of MMT program.
PMID- 29346445
TI - Transcriptome analysis of skin fibroblasts with dominant negative COL3A1
mutations provides molecular insights into the etiopathology of vascular Ehlers
Danlos syndrome.
AB - Vascular Ehlers-Danlos syndrome (vEDS) is a dominantly inherited connective
tissue disorder caused by mutations in the COL3A1 gene that encodes type III
collagen (COLLIII), which is the major expressed collagen in blood vessels and
hollow organs. The majority of disease-causing variants in COL3A1 are glycine
substitutions and in-frame splice mutations in the triple helix domain that
through a dominant negative effect are associated with the severe clinical
spectrum potentially lethal of vEDS, characterized by fragility of soft
connective tissues with arterial and organ ruptures. To shed lights into
molecular mechanisms underlying vEDS, we performed gene expression profiling in
cultured skin fibroblasts from three patients with different structural COL3A1
mutations. Transcriptome analysis revealed significant changes in the expression
levels of several genes involved in maintenance of cell redox and endoplasmic
reticulum (ER) homeostasis, COLLs folding and extracellular matrix (ECM)
organization, formation of the proteasome complex, and cell cycle regulation.
Protein analyses showed that aberrant COLLIII expression is associated with the
disassembly of many structural ECM constituents, such as fibrillins, EMILINs, and
elastin, as well as with the reduction of the proteoglycans perlecan, decorin,
and versican, all playing an important role in the vascular system. Furthermore,
the altered distribution of the ER marker protein disulfide isomerase PDI and the
strong reduction of the COLLs-modifying enzyme FKBP22 are consistent with the
disturbance of ER-related homeostasis and COLLs biosynthesis and post
translational modifications, indicated by microarray analysis. Our findings add
new insights into the pathophysiology of this severe vascular disorder, since
they provide a picture of the gene expression changes in vEDS skin fibroblasts
and highlight that dominant negative mutations in COL3A1 also affect post
translational modifications and deposition into the ECM of several structural
proteins crucial to the integrity of soft connective tissues.
PMID- 29346446
TI - Osteopontin (OPN) as a CSF and blood biomarker for multiple sclerosis: A
systematic review and meta-analysis.
AB - Identifying a reliable biomarker may accelerate diagnosis of multiple sclerosis
(MS) and lead to early management of the disease. Accumulating evidence suggest
that cerebrospinal fluid (CSF) and peripheral blood concentration of osteopontin
(OPN) may have diagnostic and prognostic value in MS. We conducted a systematic
review and meta-analysis of studies that measured peripheral blood and CSF levels
of OPN in MS patients and controls to evaluate the diagnostic potential of this
biomarker better. We searched PubMed, Web of Science and Scopus databases to find
articles that measured OPN concentration in peripheral blood and CSF samples from
MS patients up to October 19, 2016. Q statistic tests and the I2 index were
applied for heterogeneity assessment. If the I2 index was less than 40%, the
fixed-effects model was used for meta-analysis. Random-effects meta-analysis was
chosen if the I2 value was greater than 40%. After removal of duplicates, 918
articles were identified, and 27 of them fulfilled the inclusion criteria. We
included 22 eligible studies in the final meta-analysis. MS patients, in general,
had considerably higher levels of OPN in their CSF and blood when compared to all
types of controls (p<0.05). When the comparisons were made between different
subtypes of MS patients and controls, the results pointed to significantly higher
levels of OPN in CSF of MS subgroups (p<0.05). All subtypes of MS patients,
except CIS patients, had increased blood levels of OPN compared to controls
(p<0.05). In the second set of meta-analyses, we compared the peripheral blood
and CSF concentrations of OPN between MS patient subtypes. CIS patients had
significantly lower levels of OPN both in their peripheral blood and CSF compared
to patients with progressive subtypes of MS (p<0.05). CSF concentration of OPN
was significantly higher among RRMS patients compared to the CIS patients and
SPMS patients (P<0.05). Finally, patients with active MS had significantly higher
OPN levels in their CSF compared to patients with stable disease (P = 0.007). The
result of this study confirms that increased levels of OPN exist in CSF and
peripheral blood of MS patients and strengthens the evidence regarding the
clinical utility of OPN as a promising and validated biomarker for MS.
PMID- 29346447
TI - Pik3ca is required for mouse uterine gland development and pregnancy.
AB - The PI3K/AKT signaling pathway plays a critical role in the maintenance of
equilibrium between cell survival and apoptosis. The Pik3ca gene is mutated in a
range of human cancers. It has been found to be oncogenic, and mutations lead to
constitutive activation of the PI3K/AKT pathway. The expression patterns of
PIK3CA proteins in the uterus of mice during early pregnancy indicate that it may
play a role in the regulation of glandular epithelial cells, which is required to
support uterine receptivity. To further investigate the role of Pik3ca in uterine
function, Pik3ca was conditionally ablated only in the PGR-positive cells
(Pgrcre/+Pik3caf/f; Pik3cad/d). A defect of uterine gland development and
decidualization led to subfertility observed in Pik3cad/d mice. Pik3cad/d mice
showed significantly decreased uterine weight compared to Pik3caf/f mice.
Interestingly, a significant decrease of gland numbers were detected in Pik3cad/d
mice compared to control mice. In addition, we found a decrease of Foxa2
expression, which is a known uterine gland marker in Pik3cad/d mice. Furthermore,
the excessive proliferation of endometrial epithelial cells was observed in
Pik3cad/d mice. Our studies suggest that Pik3ca has a critical role in uterine
gland development and female fertility.
PMID- 29346449
TI - Within host selection for faster replicating bacterial symbionts.
AB - Wolbachia is a widespread, intracellular symbiont of arthropods, able to induce
reproductive distortions and antiviral protection in insects. Wolbachia can also
be pathogenic, as is the case with wMelPop, a virulent variant of the
endosymbiont of Drosophila melanogaster. An extensive genomic amplification of
the 20kb region encompassing eight Wolbachia genes, called Octomom, is
responsible for wMelPop virulence. The Octomom copy number in wMelPop can be
highly variable between individual D. melanogaster flies, even when comparing
siblings arising from a single female. Moreover, Octomom copy number can change
rapidly between generations. These data suggest an intra-host variability in
Octomom copy number between Wolbachia cells. Since wMelPop Wolbachia with
different Octomom copy numbers grow at different rates, we hypothesized that
selection could act on this intra-host variability. Here we tested if total
Octomom copy number changes during the lifespan of individual Drosophila hosts,
revealing selection for different Wolbachia populations. We performed a time
course analysis of Octomom amplification in flies whose mothers were controlled
for Octomom copy number. We show that despite the Octomom copy number being
relatively stable it increases slightly throughout D. melanogaster adult life.
This indicates that there is selection acting on the intra-host variation in the
Octomom copy number over the lifespan of individual hosts. This within host
selection for faster replicating bacterial symbionts may be in conflict with
between host selection against highly pathogenic Wolbachia.
PMID- 29346448
TI - A cross-sectional study to estimate prevalence of periodontal disease in a
population of dogs (Canis familiaris) in commercial breeding facilities in
Indiana and Illinois.
AB - The objectives of this cross-sectional study were: 1) to estimate the prevalence
and characterize the severity of periodontal disease in a population of dogs
housed in commercial breeding facilities; 2) to characterize PD preventive care
utilized by facility owners; and 3) to assess inter-rater reliability of a visual
scoring assessment tool. Adult dogs (N = 445) representing 42 breeds at 24 CB
facilities in Indiana and Illinois were assessed. Periodontal disease was scored
visually using the American Veterinary Dental Collage 0-IV scale. Inter-rater
reliability was assessed on 198 dogs and facility owners were asked to provide
information about the preventive care utilized. The overall prevalence of
periodontal disease (Grades I-IV) was 86.3% (95% CI: 82.9, 89.3). An ordered
logistic regression analysis found age (OR = 1.4; 95% CI 1.24, 1.54; P<0.0001),
facility (OR = 1.13; 95% CI 1.09, 1.18; P<0.0001), sex (OR = 1.7; 95% CI 1.12,
2.65; P = 0.013), and non-professional dental scaling (OR = 2.82; 95% CI 1.34,
5.91; P = 0.006) to be statistically significant. Inter-rater reliability
analysis found agreement to be 86.2%, with a weighted kappa of 0.4731 (95% CI
0.3847, 0.5615) indicating moderate agreement. Risk of periodontal disease
increased with increasing age. Additionally, a trend toward decreasing risk with
increasing weight was also found, although it was not statistically significant.
The trends identified agree with studies that have evaluated periodontal disease
in the companion dog population and do not support the assumption that the dental
health of dogs in commercial breeding facilities is worse than that of the
population as a whole. Although there were few cases of severe periodontal
disease and all facilities employed some type of preventive care in this sample,
the large number of dogs with some degree of disease (Grades I-IV) suggests that
further investigation of preventive care is warranted.
PMID- 29346450
TI - Cloning and spatiotemporal expression of Xenopus laevis Apolipoprotein CI.
AB - Apolipoprotein CI (ApoCI) belongs to the Apolipoprotein superfamily, members of
which are involved in lipid transport, uptake and homeostasis. Excessive ApoCI
has been implicated in atherosclerosis and Alzheimer's disease in humans. In this
study we report the isolation of Xenopus laevis apoCI and describe the expression
pattern of this gene during early development, using reverse transcription
polymerase chain reaction and whole mount in situ hybridization. Xenopus apoCI is
enriched in the dorsal ectoderm during gastrulation, and is subsequently
expressed in sensory placodes, neural tube and cranial neural crest. These data
suggest as yet uncharacterized roles for ApoCI during early vertebrate
embryogenesis.
PMID- 29346451
TI - An approach for predicting the compressive strength of cement-based materials
exposed to sulfate attack.
AB - In this paper, a support vector machine (SVM) model which can be used to predict
the compressive strength of mortars exposed to sulfate attack was established. An
accelerated corrosion test was applied to collect compressive strength data. For
predicting the compressive strength of mortars, a total of 638 data samples
obtained from experiment was chosen as a dataset to establish a SVM model. The
values of the coefficient of determination, the mean absolute error, the mean
absolute percentage error and the root mean square error were used for evaluating
the predictive accuracy. The main factors affecting the predicted compressive
strength were obtained by sensitivity analysis. A SVM model was calibrated,
validated, and finally established. Moreover, the performance of the SVM model
was compared to an artificial neural network (ANN) model. Results show that the
prediction values from the SVM model were close to the experimental values; the
main factors sensitive to concrete compressive strength were exposure time, water
cement ratio and sulfate ions; the performance of the SVM model was better than
the ANN model. The SVM model developed in this study can be potentially used for
predicting the compressive strength of cement-based materials servicing in harsh
environments.
PMID- 29346452
TI - Body shape indices are predictors for estimating fat-free mass in male athletes.
AB - It is unknown whether body size and body shape parameters can be predictors for
estimating whole body fat-free mass (FFM) in male athletes. This study aimed to
investigate whether body size and shape variables can be predictors for FFM in
male athletes. Using a whole-body dual-energy X-ray absorptiometry scanner, whole
body fat mass (FM) and FFM were determined in 132 male athletes and 14 sedentary
males. The sample was divided into two groups: validation (N = 98) and cross
validation (N = 48) groups. Body height (BH), body mass (BM), and waist
circumference at immediately above the iliac crest (W) were measured. BM-to-W and
W-to-BH ratios were calculated as indices of body shapes. Stepwise multiple
regression analysis revealed that BM/W and W/BH were selected as explainable
variables for predicting FFM. The equation developed in the validation group was
FFM (kg) = 0.883 * BM/W (kg/m) + 43.674 * W/BH (cm/cm)- 41.480 [R2 = 0.900, SEE
(%SEE) = 2.3 kg (3.8%)], which was validated in the cross-validation group. Thus,
the current results demonstrate that an equation using BM/W and W/BH as
independent variables is applicable for predicting FFM in male athletes.
PMID- 29346453
TI - Yearly fluctuations of flower landscape in a Mediterranean scrubland:
Consequences for floral resource availability.
AB - Species flower production and flowering phenology vary from year to year due to
extrinsic factors. Inter-annual variability in flowering patterns may have
important consequences for attractiveness to pollinators, and ultimately, plant
reproductive output. To understand the consequences of flowering pattern
variability, a community approach is necessary because pollinator flower choice
is highly dependent on flower context. Our objectives were: 1) To quantify yearly
variability in flower density and phenology; 2) To evaluate whether changes in
flowering patterns result in significant changes in pollen/nectar composition. We
monitored weekly flowering patterns in a Mediterranean scrubland community (23
species) over 8 years. Floral resource availability was estimated based on field
measures of pollen and nectar production per flower. We analysed inter-annual
variation in flowering phenology (duration and date of peak bloom) and flower
production, and inter-annual and monthly variability in flower, pollen and nectar
species composition. We also investigated potential phylogenetic effects on inter
annual variability of flowering patterns. We found dramatic variation in yearly
flower production both at the species and community levels. There was also
substantial variation in flowering phenology. Importantly, yearly fluctuations
were far from synchronous across species, and resulted in significant changes in
floral resources availability and composition at the community level. Changes
were especially pronounced late in the season, at a time when flowers are scarce
and pollinator visitation rates are particularly high. We discuss the
consequences of our findings for pollinator visitation and plant reproductive
success in the current scenario of climate change.
PMID- 29346454
TI - More Unified Analysis of Medical Imaging System SNR Characteristics.
AB - The ideal observer signal-to-noise ratio has been derived from statistical
decision theory for all of the major medical imaging modalities. This yields an
absolute scale for image performance assessment and instrumentation design and
optimization. Applications include: the functional dependence of detectable
detail size on exposure or imaging time; a framework for comparing data
acquisition techniques, e.g., Fourier methods vs reconstruction from projections
in NMR imaging; calculations of realizable limits, e.g., the limiting gain of
time-of-flight PET scanning. Measurements on human observers show that they can
come close to ideal performance, except when the noise has negative correlations
as in images reconstructed from projections. In this latter case they suffer a
small but significant penalty.
PMID- 29346455
TI - Response: Concerns with conclusions in the article by Sherwood et al 'Key
differences between 13 KRAS mutation detection technologies and their relevance
for clinical practice'.
PMID- 29346467
TI - Modification of the Associations Between Duration of Oral Contraceptive Use and
Ovarian, Endometrial, Breast, and Colorectal Cancers.
AB - Importance: Although oral contraceptive (OC) use is common, the influence of OC
use on carcinogenesis is not fully understood. A recent Agency for Healthcare
Research and Quality report identified a need to understand the consistency of OC
use and cancer associations across subpopulations, including smokers and obese
women. Objective: To determine whether associations between duration of OC use
and risk of specific cancers were modified by lifestyle characteristics. Design,
Setting, and Participants: The prospective NIH-AARP Diet and Health Study
(enrolled 1995-1996, followed until 2011), with population-based recruitment of
AARP members in 6 states and 2 metropolitan areas. All analyses included at least
100 000 women who reported OC use at enrollment. We identified 1241 ovarian, 2337
endometrial, 11 114 breast, and 3507 colorectal cancer cases during follow-up.
Data analysis was performed between September 2016 and April 2017. Exposures:
Duration of OC use (never or <1 year [reference], 1-4, 5-9, or >=10 years). Main
Outcomes and Measures: Development of ovarian, endometrial, breast, and
colorectal cancers. We examined effect modification by modifiable lifestyle
characteristics: cigarette smoking, alcohol consumption, body mass index (BMI),
and physical activity. We used Cox models adjusted for age, race, age at
menarche, and the modifiers of interest. Results: The analytic population was
aged 50 to 71 years (median, 62 years) at enrollment and largely white (91%) and
postmenopausal (96%). For ovarian cancer, OC use-associated risk reductions
strengthened with duration of use (long-term OC use [>=10 years] HR, 0.60; 95%
CI, 0.47-0.76; P < .001 for trend) and were similar across modifiable lifestyle
factors. Risk reductions for endometrial cancer strengthened with duration of use
(long-term OC use HR, 0.66; 95% CI, 0.56-0.78; P < .001 for trend); the most
pronounced reductions were among long-term OC users who were smokers (HR, 0.47;
95% CI, 0.25-0.88), had obese BMIs (0.36; 95% CI, 0.25-0.52), and who exercised
rarely (HR, 0.40; 95% CI, 0.29-0.56). Associations between OC use and breast and
colorectal cancers were predominantly null. Conclusions and Relevance: Long-term
OC use is consistently associated with reduced ovarian cancer risk across
lifestyle factors. We observed the greatest risk reductions for endometrial
cancer among women at risk for chronic diseases (ie, smokers, obese BMI). Oral
contraceptive use may be beneficial for chemoprevention for a range of women with
differing baseline cancer risks.
PMID- 29346468
TI - Congenital Restrictive Strabismus.
PMID- 29346469
TI - Identifying who lives in a care home-a challenge to be conquered.
PMID- 29346470
TI - Proposal for a New Diagnosis for Cochlear Migraine.
PMID- 29346471
TI - Use of Single-Nucleotide Polymorphisms and Mammographic Density Plus Classic Risk
Factors for Breast Cancer Risk Prediction.
AB - Importance: Single-nucleotide polymorphisms (SNPs) have demonstrated an
association with breast cancer susceptibility, but there is limited evidence on
how to incorporate them into current breast cancer risk prediction models.
Objective: To determine whether a panel of 18 SNPs (SNP18) may be used to predict
breast cancer in combination with classic risk factors and mammographic density.
Design, Setting, and Participants: This cohort study enrolled a subcohort of 9363
women, aged 46 to 73 years, without a previous breast cancer diagnosis from the
larger prospective cohort of the PROCAS study (Predicting Risk of Cancer at
Screening) specifically to evaluate breast cancer risk-assessment methods.
Enrollment took place from October 2009 through June 2015 from multiple
population-based screening centers in Greater Manchester, England. Follow-up
continued through January 5, 2017. Exposures: Genotyping of 18 SNPs, visual
assessment percentage mammographic density, and classic risk assessed by the
Tyrer-Cuzick risk model from a self-completed questionnaire at cohort entry. Main
Outcomes and Measures: The predictive ability of SNP18 for breast cancer
diagnosis (invasive and ductal carcinoma in situ) was assessed using logistic
regression odds ratios per interquartile range of the predicted risk. Results: A
total of 9363 women were enrolled in this study (mean [range] age, 59 [46-73]
years). Of these, 466 were found to have breast cancer (271 prevalent; 195
incident). SNP18 was similarly predictive when unadjusted or adjusted for
mammographic density and classic factors (odds ratios per interquartile range,
respectively, 1.56; 95% CI, 1.38-1.77 and 1.53; 95% CI, 1.35-1.74), with observed
risks being very close to expected (adjusted observed-to-expected odds ratio,
0.98; 95% CI, 0.69-1.28). A combined risk assessment indicated 18% of the
subcohort to be at 5% or greater 10-year risk, compared with 30% of all cancers,
35% of interval-detected cancers, and 42% of stage 2+ cancers. In contrast, 33%
of the subcohort were at less than 2% risk but accounted for only 18%, 17%, and
15% of the total, interval, and stage 2+ breast cancers, respectively.
Conclusions and Relevance: SNP18 added substantial information to risk assessment
based on the Tyrer-Cuzick model and mammographic density. A combined risk is
likely to aid risk-stratified screening and prevention strategies.
PMID- 29346472
TI - A Revised Estimate of Costs Associated With Routine Preoperative Testing in
Medicare Cataract Patients With a Procedure-Specific Indicator.
AB - Importance: Routine preoperative medical testing is not recommended for patients
undergoing low-risk surgery, but testing is common before surgery. A 30-day
preoperative testing window is conventionally used for study purposes; however,
the extent of routine testing that occurs prior to that point is unknown.
Objective: To improve on existing cost estimates by identifying all routine
preoperative testing that takes place after the decision is made to perform
cataract surgery. Design, Setting, and Participants: This cross-sectional study
assessed preoperative care in a 50% sample of Medicare beneficiaries older than
66 years who underwent ambulatory cataract surgery in 2011. Data analysis was
completed from March 2016 to October 2017. Main Outcomes and Measures: Using
ocular biometry as a procedure-specific indicator to mark the start of the
routine preoperative testing window, we measured testing rates in the interval
between ocular biometry and cataract surgery and compared this with testing rates
in the 6 months preceding biometry. We estimated the total cost of testing that
occurred between biometry and cataract surgery. Results: A total of 440 857
patients underwent cataract surgery. A total of 423 710 (96.1%) had an ocular
biometry claim before index surgery, of whom 264 514 (60.0%) were female; the
mean (SD) age of the cohort was 76.1 (6.2) years. A total of 111 998 (25.4%)
underwent surgery more than 30 days after biometry. Among patients with a
biometry claim, the mean number of tests/patient/month increased from 1.1 in the
baseline period to 1.7 in the interval between biometry and cataract surgery.
Although preoperative testing peaked in all patients in the 30 days preceding
surgery (1.8 tests/patient/month), the subset of patients with no overlap between
postbiometry and presurgery periods experienced increased testing rates to 1.8
tests per patient per month in the 30 days after biometry, regardless of the
elapsed time between biometry and surgery. The total estimated cost of routine
preoperative testing in the full cohort was $22.7 million; we estimate that
routine preoperative testing costs Medicare up to $45.4 million annually.
Conclusions and Relevance: In this study of Medicare beneficiaries, routine
preoperative medical testing occurs more often and is costlier than has been
reported previously. Extra costs are attributable to testing that occurs prior to
the 30-day window preceding surgery. As a cost-cutting measure, routine
preoperative medical testing should be avoided in patients with cataracts
throughout the interval between ocular biometry and cataract surgery.
PMID- 29346473
TI - Treatment for Alcohol Dependence in Primary Care Compared to Outpatient
Specialist Treatment-A Randomized Controlled Trial.
AB - Aim: To investigate if treatment for alcohol dependence in primary care is as
effective as specialist addiction care. Method: Randomized controlled non
inferiority trial, between groups parallel design, not blinded. The non
inferiority limit was set to 50 grams of alcohol per week. About 288 adults
fulfilling ICD-10 criteria for alcohol dependence were randomized to treatment in
primary care (men n = 82, women n = 62) or specialist care (men n = 77, women n =
67). General practitioners at 12 primary care centers received 1-day training in
a treatment manual for alcohol dependence. Primary outcome was change in weekly
alcohol consumption at 6-months follow-up compared with baseline, as measured
with timeline follow back. Secondary outcomes were heavy drinking days, severity
of dependence, consequences of drinking, psychological health, quality of life,
satisfaction with treatment and biomarkers. Results: Intention-to-treat analysis
(n = 228) was statistically inconclusive, and could not confirm non-inferiority
for the primary outcome, since the high end of the confidence interval exceeded
50 grams (estimated mean weekly alcohol consumption was 30 grams higher in
primary care compared with specialist care; 95% confidence interval -10.20;
69.72). However, treatment in specialist care was not significantly superior to
primary care (P = 0.146). Subanalysis suggests that specialist care was superior
to primary care only for patients with high severity of dependence. Conclusions:
Treatment for alcohol dependence in primary care is a promising approach,
especially for individuals with low to moderate dependence. This may be a way to
broaden the base of treatment for alcohol dependence, reducing the current
treatment gap.
PMID- 29346474
TI - Examining Nonparticipation in the Maternal Follow-up Within the Danish National
Birth Cohort.
AB - A follow-up questionnaire on maternal health was distributed within the Danish
National Birth Cohort (established in 1996-2002) 14 years after the index birth.
Responses were obtained from 41,466 (53.2%) of 78,010 eligible mothers. To ensure
the appropriate use of these data, the possibility of selection bias due to
nonparticipation had to be evaluated. We estimated 4 selected exposure-outcome
associations (prepregnancy weight-depression; exercise-degenerative
musculoskeletal conditions; smoking-heart disease; and alcohol consumption-breast
cancer). We adjusted for several factors associated with participation and
applied inverse probability weighting. To estimate the degree of selection bias,
we calculated relative odds ratios for the relationship between the baseline
cohort and the subset participating in the Maternal Follow-up. Participating
women were generally healthier, of higher social status, and older than the
baseline cohort. However, selection bias in the chosen scenarios was limited;
ratios of the odds ratios ranged from -14% to 5% after adjustment for age,
parity, social status, and, if the variable was not the exposure variable,
prepregnancy body mass index, exercise, smoking, and alcohol consumption.
Applying inverse probability weighting did not further reduce bias. In
conclusion, while participants differed somewhat from the baseline cohort,
selection bias was limited after factors associated with participation status
were accounted for.
PMID- 29346476
TI - Errors in Figures 1, 2, and 3.
PMID- 29346475
TI - Current Status of Radiology Training in Otolaryngology Residency Programs.
AB - Importance: Otolaryngologists use head and neck imaging on a daily basis.
However, little is known about the training residents receive on the subject.
Understanding the current training environment is important to identify areas of
improvement for resident education. Objective: To assess the current state of
radiology training in otolaryngology residency programs. Design, Setting, and
Participants: This was a cross-sectional survey of 106 otolaryngology residency
program directors involving multiple academic institutions. Main Outcomes and
Measures: The main outcome of this study is the number of US otolaryngology
residency programs that have a radiology curriculum. Measured outcomes were
obtained from an anonymous online survey and reported as a percent of total
respondents. Results: Program directors from 39 of 106 (37%) US otolaryngology
residency training programs responded to the survey. Twenty-eight of 39 (71%)
have a focused radiology curriculum; 18 of 28 (64%) conduct sessions on a monthly
basis, 8 of 28 (29%) on a quarterly basis, and 2 of 28 (7%) on a weekly basis.
The predominant format (20 of 27 programs [74%]) is a mix of case-based review of
inpatient studies and standard lectures. The largest proportion of sessions were
run by radiologists (13 of 28 [46%]), with a mix of radiology and
otolaryngologists close behind (11 of 28 [39%]). Twenty-two of 39 residency
programs (56%) have a dedicated radiology rotation within their educational
curriculum, of which 17 of 22 (77%) occur in postgraduate year 1 (PGY-1) of
training, 3 of 22 (14%) in PGY-3, and 2 of 22 (9%) in PGY-4. Rotation lengths
range from 1 week to 3 months, with most running 1 to 4 weeks. Thirty-two of 38
of US program directors (84%) believe that a formal radiology curriculum would
benefit their residents. Thirty-five of 39 believe that this should be a case
based review of images. Twenty-four of 38 believe this should be done on a
monthly basis. Fifteen of 39 responding program directors (39%) believe the
optimal time is during the PGY-3 of training, 36% (14 of 38) favor the PGY-2, and
23% (9 of 38) in PGY-1. Conclusions and Relevance: Despite no standardized
requirements from the Accreditation Council for Graduate Medical Education
(ACGME), 71% of US otolaryngology residency program directors who responded to
our survey have a radiology curriculum. Most run didactics sessions at the
desired frequency, setting, and format preferred by responding program directors.
More than half of programs provide a dedicated radiology rotation, mostly during
PGY-1, while identifying PGY-2 and PGY-3 as the optimal time for such an
experience. These results highlight the need for a more thorough review of
radiology education requirements from the ACGME to improve the training of
otolaryngology residents across the country.
PMID- 29346477
TI - Enasidenib-Induced Differentiation Syndrome in IDH2-Mutant Acute Myeloid
Leukemia.
PMID- 29346478
TI - Differentiation Syndrome Associated With Enasidenib, a Selective Inhibitor of
Mutant Isocitrate Dehydrogenase 2: Analysis of a Phase 1/2 Study.
AB - Importance: Enasidenib mesylate, a mutant isocitrate dehydrogenase 2 (IDH2)
protein inhibitor that promotes differentiation of leukemic myeloblasts, was
recently approved by the US Food and Drug Administration for use in
relapsed/refractory (R/R) mutant IDH2 acute myeloid leukemia (AML). During the
first study of enasidenib in humans, a minority of patients with advanced myeloid
neoplasms experienced unexpected signs/symptoms of a differentiation syndrome
(DS), a potentially lethal entity. Objective: To characterize IDH-inhibitor
associated DS (IDH-DS) and its effective management. Design, Setting, and
Participants: Using data obtained from a multicenter, open-label, pivotal phase
1/2 study of enasidenib, a differentiation syndrome review committee
retrospectively evaluated potential cases of IDH-DS in enasidenib-treated
patients with R/R AML. Data were collected between August 27, 2013, and October
14, 2016. The committee identified and agreed on signs and symptoms
characteristic of IDH-DS and developed an algorithm for identification and
treatment. Among 281 patients with R/R AML enrolled in the trial, the committee
identified 72 patients for review based on investigator-reported cases of DS (n =
33) or reported adverse events or signs and symptoms characteristic of IDH-DS.
Interventions: Treatment with enasidenib at a dosage of 50 to 650 mg/d was
evaluated during the dose-escalation phase, and a dosage of 100 mg/d was used in
the phase 1 expansion and phase 2, all in continual 28-day cycles. Main Outcomes
and Measures: Unexpected adverse events of IDH-DS during the phase 1/2 study.
Results: Thirty-three of the 281 patients (11.7%) were identified as having
possible or probable IDH-DS. Median age of those 33 patients was 70 years (range,
38-80 years); 20 (60.6%) were male. The most frequent manifestations were
dyspnea, fever, pulmonary infiltrates, and hypoxia. Median time to onset was 30
days (range, 7-129 days). Patients who experienced IDH-DS were less likely to
have less than 20% bone marrow blasts (6% vs 22%, P = .04) and more likely to
have undergone fewer previous anticancer regimens (median, 1.0 [range, 1-4] vs
2.0 [range, 1-14], P = .05) at study entry than those who did not. Thirteen
patients (39.4%) had concomitant leukocytosis. Isocitrate dehydrogenase
differentiation syndrome was effectively managed with systemic corticosteroids.
The enasidenib regimen was interrupted for 15 patients (45.5%), but permanent
discontinuation of treatment was not required. Conclusions and Relevance:
Isocitrate dehydrogenase differentiation syndrome is a recognizable and
potentially lethal clinical entity, occurring in approximately 12% of enasidenib
treated patients with mutant-IDH2 R/R AML. It requires prompt recognition and
management. As use of mutant IDH inhibitors increases, these findings and
recommendations are increasingly germane to care of patients with mutant-IDH
neoplasms. Trial Registration: clinicaltrials.gov Identifier: NCT01915498.
PMID- 29346479
TI - A karyozoic phenomenon for Neospora caninum.
PMID- 29346480
TI - Changing Collective Social Norms in Favour of Reduced Harmful Use of Alcohol: A
Review of Reviews.
AB - Background: Public sector bodies have called for policies and programmes to shift
collective social norms in disfavour of the harmful use of alcohol. This article
aims to identify and summarize the evidence and propose how policies and
programmes to shift social norms could be implemented and evaluated. Design:
Review of reviews for all years to July 2017. Data sources: Searches on OVID
Medline, Healthstar, Embase, PsycINFO, AMED, Social Work Abstracts, CAB
Abstracts, Mental Measurements Yearbook, Joanna Briggs Institute EBP, Health and
Psychosocial Instruments, International Pharmaceutical Abstracts, International
Political Science Abstracts, NASW Clinical Register and Epub Ahead of Print
databases. Eligibility: All reviews, without language or date restrictions
resulting from combining the terms ((review or literature review or review
literature or data pooling or comparative study or systematic review or meta
analysis or pooled analysis) and (social norms or culture) and (alcohol
drinking)). Results: Two relevant reviews were identified. One review of
community-based interventions found one study that demonstrated small changes in
parental disapproval of under-age drinking. One review stressed that collective
social norms about drinking are malleable and not uniform in any one country.
Three factors are proposed to inform programmes: provide information about the
consequences of the harmful use of alcohol, and their causes and distribution;
act on groups, not individuals; and strengthen environmental laws, regulations
and approaches. Conclusions: Purposeful policies and programmes could be
implemented to change collective social norms in disfavour of the harmful use of
alcohol; they should be evidence-based and fully evaluated for their impact.
PMID- 29346483
TI - Retreat From Human Rights and Adverse Consequences for Health.
PMID- 29346484
TI - Association of Dietary Inflammatory Potential With Colorectal Cancer Risk in Men
and Women.
AB - Importance: Inflammation is important in colorectal cancer development. Diet
modulates inflammation and may thus be a crucial modifiable factor in colorectal
cancer prevention. Objective: To examine whether proinflammatory diets are
associated with increased colorectal cancer risk by using an empirical dietary
inflammatory pattern (EDIP) score based on a weighted sum of 18 food groups that
characterizes dietary inflammatory potential based on circulating levels of
inflammation biomarkers. Design, Settings, and Participants: Cohort study of 46
804 men (Health Professionals Follow-up Study: 1986-2012) and 74 246 women
(Nurses' Health Study: 1984-2012) followed for 26 years to examine associations
between EDIP scores and colorectal cancer risk using Cox regression. We also
examined associations in categories of alcohol intake and body weight. Data
analysis began January 17, 2017, and was completed August 9, 2017. Exposures:
EDIP scores calculated from food frequency questionnaires administered every 4
years. Main Outcomes and Measures: Incident colorectal cancer. Results: We
documented 2699 incident colorectal cancer cases over 2 571 831 person-years of
follow-up. Compared with participants in the lowest EDIP quintile (Q) who had a
colorectal cancer incidence rate (per 100 000 person-years) of 113 (men) and 80
(women), those in the highest Q had an incidence rate of 151 (men) and 92
(women), leading to an unadjusted rate difference of 38 and 12 more colorectal
cancer cases, respectively, among those consuming highly proinflammatory diets.
Comparing participants in the highest vs lowest EDIP Qs in multivariable-adjusted
analyses, higher EDIP scores were associated with 44% (men: hazard ratio [HR],
1.44; 95% CI, 1.19-1.74; P < .001 for trend), 22% (women: HR, 1.22; 95% CI, 1.02
1.45; P = .007 for trend), and 32% (men and women: pooled HR, 1.32; 95% CI, 1.12
1.55; P < .001 for trend) higher risk of developing colorectal cancer. In both
men and women, associations were observed in all anatomic subsites except for the
rectum in women. In subgroups (P <= .02 for all interactions), associations
differed by alcohol intake level, with stronger associations among men (Q5 vs Q1
HR, 1.62; 95% CI, 1.05-2.49; P = .002 for trend) and women (Q5 vs Q1 HR, 1.33;
95% CI, 0.97-1.81; P = .03 for trend) not consuming alcohol; and by body weight,
with stronger associations among overweight/obese men (Q5 vs Q1 HR, 1.48; 95% CI,
1.12-1.94; P = .008 for trend) and lean women (Q5 vs Q1 HR, 1.31; 95% CI, 0.99
1.74; P = .01 for trend). Conclusions and Relevance: Findings suggest that
inflammation is a potential mechanism linking dietary patterns and colorectal
cancer development. Interventions to reduce the adverse role of proinflammatory
diets may be more effective among overweight/obese men and lean women or men and
women who do not consume alcohol.
PMID- 29346485
TI - Adverse Events in Facial Implant Surgery and Associated Malpractice Litigation.
AB - Importance: Facial implants represent an important strategy for providing instant
and long-lasting volume enhancement to address both aging and posttraumatic
defects. Objective: To better understand risks of facial implants by examining
national resources encompassing adverse events and considerations facilitating
associated litigation. Design, Setting, and Participants: A cross-sectional study
reviewed complications following facial implants. The procedures reviewed were
performed on patients at locations throughout the United States from January 2006
to December 2016. Data collection was completed in March 2017. The Manufacturer
and User Facility Device Experience database, which contains medical device
reports submitted to the US Food and Drug Administration (FDA), was searched for
complications that occurred from January 2006 to December 2016 involving facial
implants made by Implantech, MEDPOR, Stryker, KLS Martin, and Synthes.
Furthermore, the Thomson Reuters Westlaw legal database was searched for relevant
litigation. Main Outcomes and Measures: The complications of facial implants were
analyzed in relation to the location of implant and severity of complication.
Litigation was analyzed to determine which factors determine outcome. Results:
Thirty-nine instances of adverse events reported to the FDA were identified.
Sixteen (41%) involved malar implants, followed by 12 chin implants (31%). The
most common complications included infection (18 [46%]), implant migration (9
[23%]), swelling (7 [18%]), and extrusion (4 [10%]). Thirty-two patients (83%)
had to have their implants removed. Infection occurred at a mean (SD) of 83.3
(68.8) days following the surgery. One-third of complications involved either
migration or extrusion. The mean (range) time to migration or extrusion was 381.1
(10-2400) days. In 12 malpractice cases identified in publicly available court
proceedings, alleged inadequate informed consent and requiring additional
surgical intervention (ie, removal) were the most commonly cited factors.
Conclusions and Relevance: Infection and implant migration or extrusion are the
most common complications of facial implants. Most of these complications
necessitate removal. These considerations need to be discussed with patients
preoperatively as part of the informed consent process, as allegedly inadequate
informed consent was cited in a significant proportion of resultant litigation,
and there were overlapping considerations among adverse events reported to the
FDA and factors brought up in relevant litigation. Cases resolved with
settlements and jury-awarded damages encompassed considerable award totals. Level
of Evidence: NA.
PMID- 29346486
TI - Treatment Outcomes and Adverse Events Following In-Office Angiolytic Laser With
or Without Concurrent Polypectomy for Vocal Fold Polyps.
AB - Importance: In-office angiolytic laser procedures have been used successfully as
an alternative treatment for vocal fold polyps; little is known in detail about
the treatment outcomes and adverse events. Objective: To examine the outcomes and
incidence rates of adverse events associated with in-office angiolytic laser
procedures with or without concurrent polypectomy as an alternative treatment for
vocal fold polyps. Design, Setting, and Participants: Retrospective cohort study
at a tertiary medical center. We identified 114 consecutive patients with vocal
polyps who underwent in-office angiolytic laser treatments between January 1,
2014, and August 31, 2016. After the exclusion of 17 with missing or incomplete
data, 97 were enrolled. Interventions: In-office 532-nm laser procedures with or
without concurrent polypectomy. Main Outcomes and Measures: Between 1 and 2
months after the surgical procedures, we collected the following outcome data:
videolaryngostroboscopy, perceptual rating of voice quality, acoustic analysis,
maximal phonation time, and subjective rating of voice quality using a visual
analogue scale and 10-item voice handicap index. Results: This study enrolled 97
patients (mean [SD] age, 45.6 [11.3] years; 48 [49%] male). The mean duration of
symptoms was 10.1 months (range, 1-60 months). Twenty-nine patients (30%) had
angiolytic laser procedures only, while 68 (70%) received laser with concurrent
polypectomy. Both treatment modalities offered significant improvements. Only 1
patient (1%) receiving angiolytic laser with concurrent polypectomy underwent
another treatment session, so this group had significantly less need for multiple
treatments than those receiving laser treatment alone (6 [21%]; effect size,
1.57; 95% CI, -2.77 to -0.36). We identified 8 adverse events (8% of the cases):
vocal fold edema (n = 5), vocal hematoma (n = 2), and vocal ulceration (n = 1).
Patients treated with laser plus concurrent polypectomy had significantly fewer
adverse events than those treated with angiolytic laser alone (2 [3%] vs 6 [21%];
effect size, 1.20; 95% CI, 0.26 to 2.13). Conclusions and Relevance: In-office
angiolytic laser procedures can be an effective alternative treatment for vocal
polyps, although with possible need for multiple treatment sessions and
occasional occurrence of minor postoperative adverse events. Concurrent
polypectomy following laser coagulation allows less laser energy delivery and
reduces the risk of postoperative adverse events and the need for additional
treatment sessions.
PMID- 29346487
TI - Preoperative Evaluations for Cataract Surgery Are Routine but Anachronistic.
PMID- 29346488
TI - A Subretinal Cell Delivery Method via Suprachoroidal Access in Minipigs: Safety
and Surgical Outcomes.
AB - Purpose: This study evaluated a new subretinal method for delivery of human or
pig umbilical tissue-derived cells (hUTC or pUTC, respectively) using a novel
subretinal injection cannula and suprachoroidal approach in Gottingen minipig
eyes. hUTC (palucorcel) are currently under development for treating geographic
atrophy in humans. Methods: Twenty-four Gottingen minipigs (divided into eight
groups) were subretinally administered palucorcel, pUTC, or vehicle. In some
cases, fluorescently labeled cells and vehicle were administered. Conjunctival
cutdown and sclerotomy were performed, then a flexible cannula containing a
microneedle was inserted and advanced into the suprachoroidal space. The
microneedle was deployed and visualized; 50 MUL cells (target concentration, 11.2
* 106 cells/mL [560,000 cells/eye]) or vehicle was injected subretinally. Safety
outcomes were evaluated. Results: For all animals, cells and vehicle were
successfully administered. Labeled cells or fluorescent vehicle were contained in
the subretinal bleb, without leakage into the vitreous. No retinal detachment or
vitreous traction band was identified by ophthalmologic examination. At all time
points, observed microscopic changes were attributable to experimental
procedures. On histopathology immediately after injection, localized retinal
detachments were seen, along with focal retinal, choroidal, and/or scleral
discontinuities. A moderate inflammatory response was seen in a limited number of
animals. In the allogeneic setting, no antibody responses were detectable. Anti
human UTC antibodies were detected in the xenogeneic setting. Conclusions:
Palucorcel, pUTC, and vehicle were successfully administered to Gottingen
minipigs using a novel subretinal injection cannula via a suprachoroidal surgical
approach, with no significant adverse events; therefore, this technique appears
to be feasible for further clinical development.
PMID- 29346489
TI - The Suprachoroidal Delivery Route and Exploring the Potential of Cell-Based
Therapies for Age-Related Macular Degeneration.
PMID- 29346491
TI - Increased mtDNA Copy Number Does Not Protect Against LHON.
PMID- 29346490
TI - Composition, Architecture, and Functional Implications of the Connective Tissue
Network of the Extraocular Muscles.
AB - Purpose: We examined the pattern and extent of connective tissue distribution in
the extraocular muscles (EOMs) and determined the ability of the interconnected
connective tissues to disseminate force laterally. Methods: Human EOMs were
examined for collagens I, III, IV, and VI; fibronectin; laminin; and elastin
using immunohistochemistry. Connective tissue distribution was examined with
scanning electron microscopy. Rabbit EOMs were examined for levels of force
transmission longitudinally and transversely using in vitro force assessment.
Results: Collagens I, III, and VI localized to the endomysium, perimysium, and
epimysium. Collagen IV, fibronectin, and laminin localized to the basal lamina
surrounding all myofibers. All collagens localized similarly in the orbital and
global layers throughout the muscle length. Elastin had the most irregular
pattern and ran longitudinally and circumferentially throughout the length of all
EOMs. Scanning electron microscopy showed these elements to be extensively
interconnected, from endomysium through the perimysium to the epimysium
surrounding the whole muscle. In vitro physiology demonstrated force generation
in the lateral dimension, presumably through myofascial transmission, which was
always proportional to the force generated in the longitudinally oriented
muscles. Conclusions: A striking connective tissue matrix interconnects all the
myofibers and extends, via perimysial connections, to the epimysium. These
interconnections are significant and allow measurable force transmission
laterally as well as longitudinally, suggesting that they may contribute to the
nonlinear force summation seen in motor unit recording studies. This provides
strong evidence that separate compartmental movements are unlikely as no region
is independent of the rest of the muscle.
PMID- 29346492
TI - Author Response: Increased mtDNA Copy Number Protects Against LHON.
PMID- 29346495
TI - Long Term Temporal Changes in Structure and Function of Rat Visual System After
Blast Exposure.
AB - Purpose: We identify long-term ocular sequelae subsequent to experimental blast
exposure. Methods: Male Long-Evans rats were exposed to 230 kPa side-on primary
blast overpressure using a compressed air driven shock tube. Visual system
function and structure were assessed for 8 weeks after exposure using optokinetic
nystagmus and optical coherence tomography. Vitreous protein expression and
histology (TUNEL, H&E) were performed at 1 day and 1, 4, and 8 weeks. IOP was
recorded bilaterally during blast in a subset of animals. Results: Blast pressure
profiles resembled the Friedlander waveform indicative of an open field blast.
Peak IOP in directly-exposed eyes (240 kPa) was similar to peak blast
overpressure, but IOP in indirectly-exposed eyes was 30% lower. Contrast
sensitivity of blast-exposed animals decreased significantly by 20% 1 day after
blast and did not recover by 8 weeks. Significant swelling and structural damage
to the corneal epithelial and stromal layers were observed 2 weeks after blast
exposure. Swollen corneas increased 254 +/- 143 MUm from baseline by 6 weeks, and
scarring developed by 8 weeks. Histology revealed additional lens pathology 1
week after blast, suggestive of cataract development. Endothelial cell density
increased significantly in blast-exposed animals between 1 and 4 weeks.
Neurofilament heavy chain significantly increased after blast and returned to
near baseline values by 8 weeks. Inflammatory cytokine changes corroborated
ocular pathology findings. Conclusions: These data demonstrate immediate visual
dysfunction and biochemical responses, but delayed structural pathology, in
response to single primary blast exposure. The delayed pathology time course may
provide a window to implement treatment strategies for improved visual outcome.
PMID- 29346493
TI - Antimicrobial Studies Using the Therapeutic Tissue Cross-Linking Agent, Sodium
Hydroxymethylglycinate: Implication for Treating Infectious Keratitis.
AB - Purpose: Our recent studies raise the possibility of using sodium
hydroxymethylglycinate (SMG), for pharmacologic therapeutic tissue cross-linking
(TXL) of the cornea. The present study was performed to evaluate the
antimicrobial effects of SMG for potential use in treating infectious keratitis.
Methods: In initial (group 1) experiments, methicillin-sensitive Staphylococcus
aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and
Pseudomonas aeruginosa (PA) were treated with SMG (10-40 mM) for 10 to 120
minutes. In group 2 experiments, MRSA, PA, Candida albicans (CA), and vancomycin
resistant Enterococcus (VRE) were treated with SMG (20-200 mM) for 30 minutes. In
group 2 experiments, BSA and neutralizing buffer were added to provide a
proteinaceous medium, and to ensure precise control of SMG exposure times,
respectively. SMG effectiveness was quantitated based on pathogen growth
following a 24- to 48-hour incubation period. Results: In group 1 experiments, as
expected, time- and concentration-dependent bactericidal effects were noted using
MSSA. In addition, the effect of SMG (40 mM) was greatest against MSSA (99.3%),
MRSA (96.0%), and PA (97.4%) following a 2-hour exposure with lesser effects
following 30- and 10-minute exposures. In group 2 experiments, concentration
dependent bactericidal effects were confirmed for MRSA (91%), PA (99%), and VRE
(55%) for 200-mM SMG with 30-minute treatment. SMG was not as effective against
CA, with a maximum kill rate of 37% at 80 mM SMG. Conclusions: SMG solution
exhibits a dose-dependent bactericidal effect on MSSA, MRSA, and PA, with milder
effects on VRE and CA. These studies raise the possibility of using SMG TXL for
the treatment of infectious keratitis.
PMID- 29346496
TI - Melanopsin System Dysfunction in Smith-Magenis Syndrome Patients.
AB - Purpose: Smith-Magenis syndrome (SMS) causes sleep disturbance that is related to
an abnormal melatonin profile. It is not clear how the genomic disorder leads to
a disturbed synchronization of the sleep/wake rhythm in SMS patients. To evaluate
the integrity of the intrinsically photosensitive retinal ganglion cell
(ipRGC)/melanopsin system, the transducers of the light-inhibitory effect on
pineal melatonin synthesis, we recorded pupillary light responses (PLR) in SMS
patients. Methods: Subjects were SMS patients (n = 5), with molecular diagnosis
and melatonin levels measured for 24 hours and healthy controls (n = 4). Visual
stimuli were 1-second red light flashes (640 nm; insignificant direct ipRGC
activation), followed by a 470-nm blue light, near the melanopsin peak absorption
region (direct ipRGC activation). Blue flashes produce a sustained pupillary
constriction (ipRGC driven) followed by baseline return, while red flashes
produce faster recovery. Results: Pupillary light responses to 640-nm red flash
were normal in SMS patients. In response to 470-nm blue flash, SMS patients had
altered sustained responses shown by faster recovery to baseline. SMS patients
showed impairment in the expected melatonin production suppression during the
day, confirming previous reports. Conclusions: SMS patients show dysfunction in
the sustained component of the PLR to blue light. It could explain their well
known abnormal melatonin profile and elevated circulating melatonin levels during
the day. Synchronization of daily melatonin profile and its photoinhibition are
dependent on the activation of melanopsin. This retinal dysfunction might be
related to a deficit in melanopsin-based photoreception, but a deficit in rod
function is also possible.
PMID- 29346494
TI - Novel Myopia Genes and Pathways Identified From Syndromic Forms of Myopia.
AB - Purpose: To test the hypothesis that genes known to cause clinical syndromes
featuring myopia also harbor polymorphisms contributing to nonsyndromic
refractive errors. Methods: Clinical phenotypes and syndromes that have
refractive errors as a recognized feature were identified using the Online
Mendelian Inheritance in Man (OMIM) database. One hundred fifty-four unique
causative genes were identified, of which 119 were specifically linked with
myopia and 114 represented syndromic myopia (i.e., myopia and at least one other
clinical feature). Myopia was the only refractive error listed for 98 genes and
hyperopia and the only refractive error noted for 28 genes, with the remaining 28
genes linked to phenotypes with multiple forms of refractive error. Pathway
analysis was carried out to find biological processes overrepresented within
these sets of genes. Genetic variants located within 50 kb of the 119 myopia
related genes were evaluated for involvement in refractive error by analysis of
summary statistics from genome-wide association studies (GWAS) conducted by the
CREAM Consortium and 23andMe, using both single-marker and gene-based tests.
Results: Pathway analysis identified several biological processes already
implicated in refractive error development through prior GWAS analyses and animal
studies, including extracellular matrix remodeling, focal adhesion, and axon
guidance, supporting the research hypothesis. Novel pathways also implicated in
myopia development included mannosylation, glycosylation, lens development,
gliogenesis, and Schwann cell differentiation. Hyperopia was found to be linked
to a different pattern of biological processes, mostly related to organogenesis.
Comparison with GWAS findings further confirmed that syndromic myopia genes were
enriched for genetic variants that influence refractive errors in the general
population. Gene-based analyses implicated 21 novel candidate myopia genes
(ADAMTS18, ADAMTS2, ADAMTSL4, AGK, ALDH18A1, ASXL1, COL4A1, COL9A2, ERBB3, FBN1,
GJA1, GNPTG, IFIH1, KIF11, LTBP2, OCA2, POLR3B, POMT1, PTPN11, TFAP2A, ZNF469).
Conclusions: Common genetic variants within or nearby genes that cause syndromic
myopia are enriched for variants that cause nonsyndromic, common myopia. Analysis
of syndromic forms of refractive errors can provide new insights into the
etiology of myopia and additional potential targets for therapeutic
interventions.
PMID- 29346497
TI - Convergent and Divergent Validity of the Grammaticality and Utterance Length
Instrument.
AB - Purpose: This feasibility study examines the convergent and divergent validity of
the Grammaticality and Utterance Length Instrument (GLi), a tool designed to
assess the grammaticality and average utterance length of a child's prerecorded
story retell. Method: Three raters used the GLi to rate audio-recorded story
retells from 100 English-speaking preschool children. To examine convergent
validity, the results of the GLi were correlated with 2 language sample measures,
mean length of utterance in words and percentage of grammatical utterances, and
with the results of the Structured Photographic Expressive Language Test-Third
Edition (Dawson, Stout, & Eyer, 2003). To examine divergent validity, the results
of the GLi were correlated with the results of the Kaufman Brief Intelligence
Test-Second Edition (Kaufman & Kaufman, 2004). Comparisons between task
completion time for the GLi and Systematic Analysis of Language Transcripts
(SALT; Miller & Iglesias, 2010) transcription and analysis were also conducted.
Last, preliminary discriminant analysis was used to examine the diagnostic
potential of the GLi. Results: The results of this study provide evidence of
convergent and divergent validity for the GLi. The task completion time for the
GLi was considerably shorter than the SALT transcription and analysis.
Preliminary analysis of diagnostic accuracy suggests that the GLi has the
potential to be a good tool to identify children with language impairment.
Discussion: The GLi has good convergent and divergent validity and is a reliable
instrument to assess utterance length and grammaticality of prerecorded language
samples. However, SALT transcription and analysis provide a more detailed and
comprehensive analysis of the language skills of a child.
PMID- 29346498
TI - Association of Treatment for Hodgkin Lymphoma With Estrogen Receptor Status of
Subsequent Breast Cancers.
PMID- 29346499
TI - Repeatability and Agreement of Visual Acuity Using the ETDRS Number Chart,
Landolt C Chart, or ETDRS Alphabet Chart in Eyes With or Without Sight
Threatening Diseases.
AB - Importance: The Early Treatment Diabetic Retinopathy Study (ETDRS) alphabet chart
is not feasible for measuring best-corrected visual acuity (BCVA) for individuals
who are unfamiliar with the Roman alphabet. The ETDRS Landolt C chart is an
alternative, but it may not reflect true BCVA among those with confusion between
left and right. The ETDRS number chart might overcome these limitations, but
little is known regarding its reliability. Objective: To evaluate repeatability
and agreement of BCVA using the ETDRS number chart or Landolt C chart compared
with ETDRS alphabet charts in healthy and diseased eyes. Design, Setting, and
Participants: A cross-sectional study was conducted in Thailand from July 1,
2015, to June 30, 2016, among 154 adult Thai individuals. Those who could read
Roman alphabets were classified into the following 4 groups, using 1 eye per
participant: group A, which comprised 60 healthy eyes (BCVA, 20/20-20/25); group
B, which comprised 40 eyes with age-related cataract, diabetic macular edema, or
age-related macular degeneration (BCVA, 20/20-20/40); group C, which comprised 40
eyes with age-related cataract, diabetic macular edema, or age-related macular
degeneration (BCVA, 20/50-20/100); and group D, which comprised 14 eyes with age
related cataract, diabetic macular edema, or age-related macular degeneration
(BCVA, 20/125-20/200). Interventions: Two standardized 4-m BCVA measurements with
3 different Precision Vision ETDRS charts (PV number, Landolt C, and alphabet),
in random sequence, performed 30 minutes apart. Main Outcomes and Measures:
Repeatability, agreement, and testing duration of BCVA. Results: Of 154 Thai
participants (82 women and 72 men; mean [SD] age, 52.9 [18.2] years), the ETDRS
number chart had strong repeatability coefficients (group A, 0.61 [95% CI, 0.42
0.75]; group B, 0.87 [95% CI, 0.78-0.93]; group C, 0.81 [95% CI, 0.67-0.90]; and
group D, 0.81 [95% CI, 0.49-0.94]). Concordance correlation coefficients between
the number and alphabet charts were also strong (group A, 0.89 [95% CI, 0.82
0.93]; group B, 0.97 [95% CI, 0.94-0.98]; group C, 0.92 [95% CI, 0.86-0.96]; and
group D, 0.96 [95% CI, 0.87-0.99]), while the concordance correlation
coefficients between the Landolt C and alphabet charts were lower (group A, 0.72
[95% CI, 0.52-0.83]; group B, 0.83 [95% CI, 0.68-0.91]; group C, 0.79 [95% CI,
0.61-0.89]; and group D, 0.89 [95% CI, 0.66-0.97]). The mean letter score
difference between the number and alphabet charts was 1 (95% limits of agreement,
-4 to +6) compared with -7 (95% limits of agreement, -18 to +5; P < .001) between
the Landolt C and alphabet charts. Conclusions and Relevance: The repeatability
coefficients and concordance correlation coefficients suggest that ETDRS number
charts are viable for measuring BCVA in clinical practice and trials for
individuals who are unfamiliar with the Roman alphabet.
PMID- 29346500
TI - Commentary: Alcohol and Alcoholism Special Issue on 'Alcohol and Liver
Transplantation'.
PMID- 29346503
TI - p53beta: a new prognostic marker for patients with clear-cell renal cell
carcinoma from 5.3 years of median follow-up.
AB - We previously reported six different p53 isoforms in renal cell carcinoma (RCC).
In the present study, influences of p53beta on recurrence-free survival (RFS) and
overall survival (OS) were evaluated. Patients diagnosed with RCC in our center
were into this study. mRNA expressions of p53 isoforms (p53alpha, p53beta,
p53gamma) in tumors were determined by RT-PCR and real-time PCR. Functional yeast
based assay was performed to analyze p53 mutational status. p53beta transfected
786-O and CAKi-1 cells were cultured to examine expressions of B-cell lymphoma 2
associated X protein (bax) and caspase-3, and ratios of apoptosis. After
surgeries, all patients were followed up at programmed intervals. 266 patients
were analyzed in this study. Median follow-up time was 5.3 years. RT-PCR (r =
0.72, P = 0.016) and real-time PCR (r = -0.65, P = 0.033) both showed only
p53beta expressed higher level in lower tumor stage versus higher stage. p53 wild
type and p53 mutation had comparable RFS (P = 0.361) and OS (P = 0.218),
respectively. Kaplan-Meier analysis showed high p53beta expression was associated
with significantly improved RFS and OS, regardless of p53 mutational status. High
p53beta expression indicated better RFS [hazard ratio (HR) 2.599, 95% confidence
interval (CI) 1.472-4.551, P = 0.038] and OS (HR 2.604, 95% CI 1.453-4.824, P =
0.031). p53beta transfected 786-O and CAKi-1 cells expressed significantly higher
level of bax and caspase-3, and had higher ratios of apoptosis than untransfected
cells. Taken together, higher level of p53beta predict better prognosis in
patients with RCC through enhancing apoptosis in tumors.
PMID- 29346505
TI - Clustering single cells: a review of approaches on high-and low-depth single-cell
RNA-seq data.
PMID- 29346504
TI - BAUM: improving genome assembly by adaptive unique mapping and local overlap
layout-consensus approach.
AB - Motivation: It is highly desirable to assemble genomes of high continuity and
consistency at low cost. The current bottleneck of draft genome continuity using
the second generation sequencing (SGS) reads is primarily caused by uncertainty
among repetitive sequences. Even though the single-molecule real-time sequencing
technology is very promising to overcome the uncertainty issue, its relatively
high cost and error rate add burden on budget or computation. Many long-read
assemblers take the overlap-layout-consensus (OLC) paradigm, which is less
sensitive to sequencing errors, heterozygosity and variability of coverage.
However, current assemblers of SGS data do not sufficiently take advantage of the
OLC approach. Results: Aiming at minimizing uncertainty, the proposed method
BAUM, breaks the whole genome into regions by adaptive unique mapping; then the
local OLC is used to assemble each region in parallel. BAUM can (i) perform
reference-assisted assembly based on the genome of a close species (ii) or
improve the results of existing assemblies that are obtained based on short or
long sequencing reads. The tests on two eukaryote genomes, a wild rice Oryza
longistaminata and a parrot Melopsittacus undulatus, show that BAUM achieved
substantial improvement on genome size and continuity. Besides, BAUM
reconstructed a considerable amount of repetitive regions that failed to be
assembled by existing short read assemblers. We also propose statistical
approaches to control the uncertainty in different steps of BAUM. Availability
and implementation:
http://www.zhanyuwang.xin/wordpress/index.php/2017/07/21/baum. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 29346506
TI - Small and surrounded: population size and land use intensity interact to
determine reliance on autonomous selfing in a monocarpic plant.
AB - Background and Aims: Habitat fragmentation has transformed landscapes globally,
leaving remnants embedded within a complex matrix that is rapidly becoming more
developed. For many plant populations, the associated factors of decreased size
and intensification of land use surrounding them are expected to increase pollen
limitation ('PL'), unless autonomous self-pollination provides reproductive
assurance ('RA'). Decreased pollinator visitation is often assumed to drive these
patterns, but other, less studied mechanisms might include increased
heterospecific pollen transfer or decreased conspecific pollen availability via
florivory. I investigate how PL and RA and their potential underlying mechanisms
vary with population size and land use intensity surrounding populations in the
biennial Sabatia angularis (Gentianaceae). Methods: I estimated the capacity for
seed production via autonomous self-pollination (i.e. autofertility). Over 2
years in 22 S. angularis populations across a fragmented landscape, I performed
emasculation and pollen supplementation experiments measuring RA and PL, and
quantified visitation rates of potential pollinators and a pollen consumer,
conspecific pollen loads and rates of heterospecific pollen deposition. Key
results: Autofertility based on fruit mass was 93 % under PL but only 51.6 %
relative to maximal conditions. PL and RA were significant on average across
populations in the first year of study. Variation in RA was significantly
influenced by the interaction between population size and land use intensity,
which in turn rendered PL independent of these factors. Visitation and
heterospecific pollen deposition rates were greatest in small populations and
declined with population size, while conspecific pollen loads were greatest in
intermediate sized populations. Conclusions: Increased reliance on RA is
predicted in small S. angularis populations surrounded by intense development,
which can explain elevated selfing rates in fragmented populations of plant
species more generally. Results from this study point toward forces such as
heterospecific pollen transfer, self-pollen limitation or resource availability
influencing the need and ability to rely on RA.
PMID- 29346508
TI - Oroxylin A, a natural compound, mitigates the negative effects of TNFalpha
treated acute myelogenous leukemia cells.
AB - Tumor necrosis factor alpha (TNFalpha) is a complicated cytokine which is
involved in proliferation and differentiation of acute myelogenous leukemia (AML)
cells through a poorly understood mechanism. Mechanistic studies indicate that
TNFalpha induced binding of PI3K subunit p85alpha to N-terminal truncated nuclear
receptor RXRalpha (tRXRalpha) proteins, and activated AKT. The activated PI3K/AKT
pathway negatively regulated differentiation of AML cells through the
upregulation of c-Myc. In addition, TNFalpha also induced activation of nuclear
factor kappaB (NF-kappaB), a nuclear transcription factor which was shown to
promote cell proliferation. The present study demonstrates that oroxylin A, a
natural compound isolated from Scutellariae radix, sensitizes leukemia cells to
TNFalpha and markedly enhances TNFalpha-induced growth inhibition and
differentiation of AML cell including human leukemia cell lines and primary AML
cells. Activation of PI3K/AKT pathway could be inhibited by oroxylin A through
inhibiting expression of tRXRalpha in NB4 and HL-60-resistant cells. Furthermore,
we found that oroxylin A inhibited the activation of NF-kappaB and the DNA
binding activity by TNFalpha proved by EMSA in these two AML cell lines.
Moreover, in vivo studies showed that treatment with oroxylin A in combination
with TNFalpha decreased AML cell population and prolonged survival in NOD/SCID
mice with xenografts of primary AML cells. Overall, our results indicate that
oroxylin A is able to inhibit the negative effects of TNFalpha for AML therapy,
suggesting that combination of oroxylin A and TNFalpha have the potential to
delay growth or eliminate the abnormal leukemic cells, thus representing a
promising strategy for AML treatment.
PMID- 29346509
TI - A distance-based approach for testing the mediation effect of the human
microbiome.
AB - Motivation: Recent studies have revealed a complex interplay between environment,
the human microbiome and health and disease. Mediation analysis of the human
microbiome in these complex relationships could potentially provide insights into
the role of the microbiome in the etiology of disease and, more importantly, lead
to novel clinical interventions by modulating the microbiome. However, due to the
high dimensionality, sparsity, non-normality and phylogenetic structure of
microbiome data, none of the existing methods are suitable for testing such
clinically important mediation effect. Results: We propose a distance-based
approach for testing the mediation effect of the human microbiome. In the
framework, the nonlinear relationship between the human microbiome and
independent/dependent variables is captured implicitly through the use of sample
wise ecological distances, and the phylogenetic tree information is conveniently
incorporated by using phylogeny-based distance metrics. Multiple distance metrics
are utilized to maximize the power to detect various types of mediation effect.
Simulation studies demonstrate that our method has correct Type I error control,
and is robust and powerful under various mediation models. Application to a real
gut microbiome dataset revealed that the association between the dietary fiber
intake and body mass index was mediated by the gut microbiome. Availability and
implementation: An R package 'MedTest' is freely available at
https://github.com/jchen1981/MedTest. Contact: zhiwei@njit.edu or
chen.jun2@mayo.edu. Supplementary information: Supplementary data are available
at Bioinformatics online.
PMID- 29346507
TI - Activity and safety of afatinib in a window preoperative EORTC study in patients
with squamous cell carcinoma of the head and neck (SCCHN).
AB - Background: To investigate the activity and safety of afatinib in the
preoperative treatment of squamous cell carcinoma of the head and neck (SCCHN).
Patients and methods: This study was an open-label, randomized, multicenter,
phase II window of opportunity trial. Treatment-naive SCCHN patients selected for
primary curative surgery were randomized (5 : 1 ratio) to receive afatinib during
14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumor
biopsies, 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography
(FDG-PET), and magnetic resonance imaging (MRI) were carried out at diagnosis and
just before surgery. The primary end point was metabolic FDG-PET response
(according to EORTC guidelines). Other end points included response assessment
based on the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, dynamic
contrast-enhanced (DCE)-MRI, diffusion weighted (DW)-MRI, safety, and
translational research (TR). Results: Thirty patients were randomized: 25 to
afatinib and 5 to control arm. Of the 23 eligible patients randomized to
afatinib, 16 (70%; 95% CI: 47% to 87%) patients had a partial metabolic FDG-PET
response (PMR). Five patients (22%; 95% CI: 8% to 44%) showed a partial response
by RECISTv1.1. Responses assessed via DCE-MRI and DWI-MRI did not show a strong
association with PMR or RECIST. One patient discontinued afatinib after 11 days
for grade 3 diarrhea with subsequent renal failure and 24 days delay in surgery.
No grade 4 toxicities or surgical comorbidities related to afatinib were
reported. TR results indicated that PMR was more frequent in the tumors with high
Cluster3-hypoxia score expression and with TP53 wild type. Conclusion: Afatinib
given for 2 weeks to newly diagnosed SCCHN patients induces a high rate of FDG
PET partial metabolic response and partial response according to RECISTv1.1.
Afatinib can be safely administered before surgery. Although exploratory, the
hypoxic gene signature needs further investigations as a predictive biomarker of
afatinib activity. Clinical trial registration: ClinicalTrials.gov: NCT01538381.
PMID- 29346510
TI - VIPER: a web application for rapid expert review of variant calls.
AB - Summary: With the rapid development in next-generation sequencing, cost and time
requirements for genomic sequencing are decreasing, enabling applications in many
areas such as cancer research. Many tools have been developed to analyze genomic
variation ranging from single nucleotide variants to whole chromosomal
aberrations. As sequencing throughput increases, the number of variants called by
such tools also grows. Often employed manual inspection of such calls is thus
becoming a time-consuming procedure. We developed the Variant InsPector and
Expert Rating tool (VIPER) to speed up this process by integrating the
Integrative Genomics Viewer into a web application. Analysts can then quickly
iterate through variants, apply filters and make decisions based on the generated
images and variant metadata. VIPER was successfully employed in analyses with
manual inspection of more than 10 000 calls. Availability and implementation:
VIPER is implemented in Java and Javascript and is freely available at
https://github.com/MarWoes/viper. Contact: marius.woeste@uni-muenster.de.
Supplementary information: Supplementary data are available at Bioinformatics
online.
PMID- 29346511
TI - Sleep and Health in Older Adulthood: Recent Advances and the Path Forward.
PMID- 29346512
TI - Validation of the Pediatric Infectious Diseases Society-Infectious Diseases
Society of America Severity Criteria in Children With Community-Acquired
Pneumonia.
AB - Background: The Pediatric Infectious Diseases Society (PIDS)-Infectious Diseases
Society of America (IDSA) guideline for community-acquired pneumonia (CAP)
recommends intensive care unit (ICU) admission or continuous monitoring for
children meeting severity criteria. Our objective was to validate these criteria.
Methods: This was a retrospective cohort study of children aged 3 months-18 years
diagnosed with CAP in a pediatric emergency department (ED) from September 2014
through August 2015. Children with chronic conditions and recent ED visits were
excluded. The primary predictor was the PIDS-IDSA severity criteria. Outcomes
included disposition, and interventions and diagnoses that necessitated
hospitalization (ie, need for hospitalization [NFH]). Results: Of 518 children,
56.6% were discharged; 54.3% of discharged patients and 80.8% of those
hospitalized for less than 24 hours were classified as severe. Of those admitted,
10.7% did not meet severity criteria; 69.5% met PIDS-IDSA severity criteria. Of
those children, 73.1% did not demonstrate NFH. The areas under the receiver
operator characteristic curves (AUC) for PIDS-IDSA major criteria were 0.63 and
0.51 for predicting disposition and NFH, respectively. For PIDS-IDSA minor
criteria, the AUC was 0.81 and 0.56 for predicting disposition and NFH,
respectively. The sensitivity, specificity, and likelihood ratios (LR)+ and LR-
of the PIDS-IDSA criteria were 89%, 46%, 1.65, and 0.23 for disposition and 95%,
16%, 1.13, and 0.31 for NFH. Conclusions: More than half of children classified
as severe by PIDS-IDSA criteria were not hospitalized. The PIDS-IDSA CAP severity
criteria have only fair ability to predict the need for hospitalization. New
predictive tools specifically for children are required to improve clinical
decision making.
PMID- 29346513
TI - Pancancer analysis identifies prognostic high-APOBEC1 expression level implicated
in cancer in-frame insertions and deletions.
AB - Genome insertions and deletions (indels) show tremendous functional impacts
despite they are much less common than single nucleotide variants, which are at
the center of studies assessing cancer mutational signatures. We studied 8891
tumor samples of 32 types from The Cancer Genome Atlas in order to explore those
genes which are potentially implicated in cancer indels. Survival analysis
identified in-frame indels as the most important variants predicting adverse
outcome. Transcriptome-wide association study identified 16 genes overexpressed
in both tumor samples and tumor types with high number of in-frame indels, of
whom four (APOBEC1, BCL2L15, FOXL1 and PDX1) were identified with gene products
distributed within the nucleus. APOBEC1 emerged as the mere consistently
hypomethylated gene in tumor samples with high number of in-frame indels. The
correlation of APOBEC1 expression levels with cancer indels was independent of
age and defects in DNA homologous recombination (HR) and/or mismatch repair.
Unlike frame-shift indels, triplet repeat motifs were found to occur frequently
at in-frame indel sites. The splicing variant 3, making a shorter isoform b,
showed essentially all the same indel correlations as of APOBEC1. Expression
levels of both APOBEC1 and variant 3 were found to be predicting adverse
prognosis independent of DNA HR and mismatch repair. Not less importantly, high
level of variant 3 in paired normal tissues was also proved to predict cancer
outcome. Our findings propose APOBEC1 and isoform b as the potential endogenous
mutators implicated in cancer in-frame indels and pave the way for their use as
novel prognostic tumor markers.
PMID- 29346514
TI - Optimal water networks in protein cavities with GAsol and 3D-RISM.
AB - Motivation: Water molecules in protein binding sites play essential roles in
biological processes. The popular 3D-RISM prediction method can calculate the
solvent density distribution within minutes, but is difficult to convert it into
explicit water molecules. Results: We present GAsol, a tool that is capable of
finding the network of water molecules that best fits a particular 3D-RISM
density distribution in a fast and accurate manner and that outperforms other
available tools by finding the globally optimal solution thanks to its genetic
algorithm. Availability and implementation: https://github.com/accsc/GAsol. BSD 3
clauses license. Contact: alvaro.x.cortes@gsk.com. Supplementary information:
Supplementary data are available at Bioinformatics online.
PMID- 29346515
TI - A brain-based pain facilitation mechanism contributes to painful diabetic
polyneuropathy.
AB - The descending pain modulatory system represents one of the oldest and most
fundamentally important neurophysiological mechanisms relevant to pain. Extensive
work in animals and humans has shown how a functional imbalance between the
facilitatory and inhibitory components is linked to exacerbation and maintenance
of persistent pain states. Forward translation of these findings into clinical
populations is needed to verify the relevance of this imbalance. Diabetic
polyneuropathy is one of the most common causes of chronic neuropathic pain;
however, the reason why ~25-30% of patients with diabetes develop pain is not
known. The current study used a multimodal clinical neuroimaging approach to
interrogate whether the sensory phenotype of painful diabetic polyneuropathy
involves altered function of the ventrolateral periaqueductal grey-a key node of
the descending pain modulatory system. We found that ventrolateral periaqueductal
grey functional connectivity is altered in patients suffering from painful
diabetic polyneuropathy; the magnitude of which is correlated to their
spontaneous and allodynic pain as well as the magnitude of the cortical response
elicited by an experimental tonic heat paradigm. We posit that ventrolateral
periaqueductal grey-mediated descending pain modulatory system dysfunction may
reflect a brain-based pain facilitation mechanism contributing to painful
diabetic polyneuropathy.
PMID- 29346516
TI - Deletion of Nrip1 Extends Female Mice Longevity, Increases Autophagy, and Delays
Cell Senescence.
AB - Using age of female sexual maturation as a biomarker, we previously identified
nuclear receptor interacting protein 1 (Nrip1) as a candidate gene that may
regulate aging and longevity. In the current report, we found that the deletion
of Nrip1 can significantly extend longevity of female mice (log-rank test, p =
.0004). We also found that Nrip1 expression is altered differently in various
tissues during aging and under diet restriction. Remarkably, Nrip1 expression is
elevated with aging in visceral white adipose tissue (WAT), but significantly
reduced after 4 months of diet restriction. However, in gastrocnemius muscle,
Nrip1 expression is significantly upregulated after the diet restriction. In
mouse embryonic fibroblasts, we found that the deletion of Nrip1 can suppress
fibroblast proliferation, enhance autophagy under normal culture or amino acid
starvation conditions, as well as delay oxidative and replicative senescence.
Importantly, in WAT of old animals, the deletion of the Nrip could significantly
upregulate autophagy and reduce the number of senescent cells. These results
suggest that deleting Nrip1 can extend female longevity, but tissue-specific
deletion may have varying effects on health span. The deletion of Nrip1 in WAT
may delay senescence in WAT and extend health span.
PMID- 29346517
TI - Does Telomere Length Indicate Biological, Physical, and Cognitive Health Among
Older Adults? Evidence from the Health and Retirement Study.
AB - Telomere length (TL) has been suggested as a biomarker that can indicate
individual variability in the rate of aging. Yet, it remains unclear whether TL
is related to recognized indicators of health in an aging, older nationally
representative sample. We examine whether TL is associated with 15 biological,
physical, and cognitive markers of health among older adults ages 54+. TL was
assayed from saliva using quantitative polymerase chain reaction (T/S ratio) in
the 2008 Health and Retirement Study (n = 4,074). We estimated probability of
high-risk levels across indictors of health by TL and age-singly and jointly. TL
was associated with seven indicators of poor functioning: high-density
lipoprotein and total cholesterol, cystatin C, pulse pressure, body mass index,
lung function, and walking speed. However, after adjusting for age, associations
were substantially attenuated; only associations with cholesterol and lung
function remained significant. Additionally, findings show TL did not add to the
predictive power of chronological age in predicting poor functioning. While TL
may not be a useful clinical marker of functional aging in an older adult
population, it may still play an important role in longitudinal studies in young
and middle aged populations that attempt to understand aging.
PMID- 29346518
TI - Determinants of Health Trajectories in England and the United States: An Approach
to Identify Different Patterns of Healthy Aging.
AB - Background: Aging is a multidimensional process with a remarkable interindividual
variability. This study is focused on identifying groups of population with
similar aging patterns, and to define the health trajectories of these groups.
Sociodemographic and health determinants of these trajectories are also
identified. Methods: Data from the English Longitudinal Study of Aging (ELSA) and
the Health and Retirement Study (HRS) were used. A set of self-reported health
items and measured tests were used to generate a latent health metric by means of
a Bayesian multilevel IRT model, assessing the ability of the metric to predict
mortality. Then, a Growth Mixture Model (GMM) was conducted in each study to
identify latent classes and assess health trajectories. Kaplan-Meier survival
curves were obtained for each class and a multinomial logistic regression was
used to identify determinants of these trajectories. Results: The health score
generated showed an adequate ability to predict mortality over 10 years in ELSA
(AUC = 0.74; 95% CI: 0.72, 0.75) and HRS (AUC = 0.74; 95% CI: 0.73, 0.75). By
means of GMM, four latent classes were identified in ELSA and five in HRS.
Chronic conditions, no qualification and low level of household wealth were
associated to the classes which showed a higher mortality in both studies.
Conclusion: The method based on the creation of a common metric of health and the
use of GMM to identify similar patterns of aging, allows for the comparison of
trajectories of health across longitudinal surveys. Multimorbidity, educational
level, and household wealth could be considered as determinants associated to
these trajectories.
PMID- 29346519
TI - Final results of a multi-institutional phase II trial of reirradiation with
concurrent weekly cisplatin and cetuximab for recurrent or second primary
squamous cell carcinoma of the head and neck.
AB - Background: The optimal regimen of chemotherapy and reirradiation (re-XRT) for
recurrent head and neck squamous cell carcinoma (HNSCC) is controversial. We
report the final outcomes of a multicenter phase II trial evaluating cetuximab
and cisplatin-based chemotherapy concurrent with re-XRT for patients with
recurrent HNSCC. Materials and methods: Patients with unresectable recurrent
disease or positive margins after salvage surgery arising within a previously
irradiated field with KPS >= 70 were eligible for this trial. Cetuximab 400 mg/m2
was delivered as a loading dose in week 1 followed by weekly cetuximab 250 mg/m2
and cisplatin 30 mg/m2 concurrent with 6 weeks of intensity-modulated
radiotherapy to a dose of 60-66 Gy in 30 daily fractions. Patients who previously
received both concurrent cetuximab and cisplatin with radiation or who received
radiotherapy less than 6 months prior were ineligible. Results: From 2009 to
2013, 48 patients enrolled on this trial, 2 did not receive any protocol
treatment. Of the remaining 46 patients, 34 were male and 12 female, with a
median age of 62 years (range 36-85). Treatment was feasible and only 1 patient
did not complete the treatment course. Common grade 3 or higher acute toxicities
were lymphopenia (46%), pain (22%), dysphagia (13%), radiation dermatitis (13%),
mucositis (11%) and anorexia (11%). There were no grade 5 acute toxicities. Eight
grade 3 late toxicities were observed, four of which were swallowing related.
With a median follow-up of 1.38 years, the 1-year overall survival (OS) was 60.4%
and 1-year recurrence-free survival was 34.1%. On univariate analysis, OS was
significantly improved with young age (P = 0.01). OS was not associated with
radiation dose, surgery before re-XRT or interval from prior XRT. Conclusions:
Concurrent cisplatin and cetuximab with re-XRT is feasible and offers good
treatment outcomes for patients with high-risk features. Younger patients had
significantly improved OS. ClinicalTrials.Gov Identifier: NCT00833261.
PMID- 29346520
TI - Uncovering the links between systemic hormones and oncogenic signaling in the
pathogenesis of meningioma.
PMID- 29346522
TI - Serious Fall Injury History and Adverse Health Outcomes After Initiating
Hemodialysis Among Older U.S. Adults.
AB - Background: Although older adults with predialysis chronic kidney disease are at
higher risk for falls, the prognostic significance of a serious fall injury prior
to dialysis initiation has not been well described in the end-stage renal disease
population. Methods: We examined the association between a serious fall injury in
the year prior to starting hemodialysis and adverse health outcomes in the year
following dialysis initiation using a retrospective cohort study of U.S. Medicare
beneficiaries >= 67 years old who initiated dialysis in 2010-2012. Serious fall
injuries were defined using diagnostic codes for falls plus an injury (fracture,
joint dislocation, or head injury). Health outcomes, defined as time-to-event
variables within the first year of dialysis, included four outcomes: a subsequent
serious fall injury, hospital admission, post-acute skilled nursing facility
(SNF) utilization, and mortality. Results: Among this cohort of 81,653 initiating
hemodialysis, 2,958 (3.6%) patients had a serious fall injury in the year prior
to hemodialysis initiation. In the first year of dialysis, 7.6% had a subsequent
serious fall injury, 67.6% a hospitalization, 30.7% a SNF claim, and 26.1% died.
Those with versus without a serious fall injury in the year prior to hemodialysis
initiation were at higher risk (hazard ratio, 95% confidence interval) for a
subsequent serious fall injury (2.65, 2.41-2.91), hospitalization (1.11, 1.06
1.16), SNF claim (1.40, 1.30-1.50), and death (1.14, 1.06-1.22). Conclusions: For
older adults initiating dialysis, a history of a serious fall injury may provide
prognostic information to support decision making and establish expectations for
life after dialysis initiation.
PMID- 29346523
TI - Association Between Timed Up and Go Test and Future Dementia Onset.
AB - Background: This study evaluated whether baseline results of the Timed Up and Go
(TUG) test is associated with future dementia occurrence. Methods: Using the
Korean National Health Insurance Service-National Health Screening Cohort
database, we identified 49,283 subjects without a dementia diagnosis who
participated in the National Screening Program for Transitional Ages at 66 years
of age during 2007-2012. Gait impairment was defined as taking longer than 10
seconds to perform the TUG test. Dementia occurrence was defined by the first
prescription for acetylcholinesterase inhibitors or N-Methyl-D-Aspartate receptor
antagonist with an International Classification of Diseases 10th Revision (ICD
10) code for dementia (F00, F01, F02, F03, G30, F051, or G311) during 2007-2013.
Cox proportional hazard regression models were used to assess the hazard ratios
for dementia occurrence according to baseline TUG test results. Results: Mean
follow-up period was 3.8 years. Incidence rates of dementia were 4.6 and 6.8
cases per 1,000 person-years in the normal and impaired TUG groups, respectively.
The impaired TUG group showed a higher risk of total dementia incidence (adjusted
hazard ratio [aHR], 1.34; 95% confidence interval [95% CI], 1.14-1.57). Subtype
analysis showed that the impaired TUG group had a higher risk of Alzheimer's
disease (aHR, 1.26; 95% CI, 1.06-1.51) and vascular dementia (aHR, 1.65; 95% CI,
1.19-2.30). Conclusions: The TUG test result was associated with future dementia
occurrence. More vigilant follow-up and early intervention to prevent dementia
would benefit elderly people with impaired TUG test result.
PMID- 29346521
TI - The intracellular and intercellular cross-talk during subsidiary cell formation
in Zea mays: existing and novel components orchestrating cell polarization and
asymmetric division.
AB - Background: Formation of stomatal complexes in Poaceae is the outcome of three
asymmetric and one symmetric cell division occurring in particular leaf
protodermal cells. In this definite sequence of cell division events, the
generation of subsidiary cells is of particular importance and constitutes an
attractive model for studying local intercellular stimulation. In brief, an
induction stimulus emitted by the guard cell mother cells (GMCs) triggers a
series of polarization events in their laterally adjacent protodermal cells. This
signal determines the fate of the latter cells, forcing them to divide
asymmetrically and become committed to subsidiary cell mother cells (SMCs).
Scope: This article summarizes old and recent structural and molecular data
mostly derived from Zea mays, focusing on the interplay between GMCs and SMCs,
and on the unique polarization sequence occurring in both cell types. Recent
evidence suggests that auxin operates as an inducer of SMC
polarization/asymmetric division. The intercellular auxin transport is
facilitated by the distribution of a specific transmembrane auxin carrier and
requires reactive oxygen species (ROS). Interestingly, the local differentiation
of the common cell wall between SMCs and GMCs is one of the earliest features of
SMC polarization. Leucine-rich repeat receptor-like kinases, Rho-like plant
GTPases as well as the SCAR/WAVE regulatory complex also participate in the
perception of the morphogenetic stimulus and have been implicated in certain
polarization events in SMCs. Moreover, the transduction of the auxin signal and
its function are assisted by phosphatidylinositol-3-kinase and the products of
the catalytic activity of phospholipases C and D. Conclusion: In the present
review, the possible role(s) of each of the components in SMC polarization and
asymmetric division are discussed, and an overall perspective on the mechanisms
beyond these phenomena is provided.
PMID- 29346524
TI - Effects of a Primary Care-Based Multifactorial Intervention on Physical and
Cognitive Function in Frail, Elderly Individuals: A Randomized Controlled Trial.
AB - Background: Detecting and managing frailty at early stages can prevent disability
and other adverse outcomes. The study aim was to evaluate whether a
multifactorial intervention program could modify physical and cognitive frailty
parameters in elderly individuals. Methods: We conducted a multicenter,
randomized, single-blind, parallel-group trial in community-living prefrail/frail
elderly individuals in Barcelona. A total of 352 patients, aged >=65 years old
with positive frailty screening, was randomized into two groups to receive a 12
week multidisciplinary intervention or usual care, with concealed allocation. The
intervention consisted of: exercise training, intake of hyperproteic nutritional
shakes, memory training, and medication review. Main outcome assessments with
multivariate analysis were conducted at 3 and 18 months. Results: A total of 347
participants (98.6%) completed the study, mean age 77.3 years, 89 prefrail
subjects (25.3%), and 75.3% female (n = 265). Eighteen-month assessments were
performed in 76% of the sample. After 3 and 18 months, adjusted means difference
between-groups showed significant improvements for the intervention group in all
comparisons: Short Physical Performance Battery score improved 1.58 and 1.36
points (p < .001), handgrip strength 2.84 and 2.49 kg (p < .001), functional
reach 4.3 and 4.52 cm (p < .001), and number of prescriptions decreased 1.39 and
1.09 (p < .001), respectively. Neurocognitive battery also showed significant
improvements across all dimensions at 3 and 18 months. Conclusions: A physical,
nutritional, neurocognitive, and pharmacological multifaceted intervention was
effective in reversing frailty measures both at short-term and 18 months. Lasting
benefits of a multi-intervention program among frail elderly individuals
encourage its prioritization.
PMID- 29346525
TI - Frailty Syndrome and Genomic Instability in Older Adults: Suitability of the
Cytome Micronucleus Assay As a Diagnostic Tool.
AB - Frailty, a condition involving increased risk of disability and mortality in
older adults, has emerged as a reliable way to predict the effect of aging.
Genomic instability may help to anticipate recognition of frail individuals and
improving frailty outcomes. Our objective was to evaluate the potential of the
micronucleus frequency, evaluated in lymphocytes and buccal cells, to anticipate
frailty identification and improve diagnosis reliability. Our results, from a
group of older adults over 65, showed that frail individuals had significantly
higher frequencies of micronucleus in lymphocytes (19.16 +/- 0.66 vs. 13.07 +/-
0.78, p < .001) and of binucleated buccal cells (82.65 +/- 3.42 vs. 37.16 +/-
2.85, p < .001) and lower frequencies of pyknotic and condensed chromatin buccal
cells, than nonfrail subjects. When cognitive status was considered, similar
results were obtained. Moreover, the presence of frailty and cognitive impairment
were independently related to increases in frequencies of lymphocyte micronucleus
and binucleated buccal cells. Our results encourage the use of micronucleus
frequency in lymphocytes as a complement to clinical parameters in frailty
identification. However, these results have to be further evaluated in prefrail
patients, to better understand the connection between genomic instability and
frailty and to establish these parameters as actual biomarkers of frailty in
clinical practice.
PMID- 29346526
TI - What Is the Impact of Physical Activity and Physical Function on the Development
of Multimorbidity in Older Adults Over Time? A Population-Based Cohort Study.
AB - Background: Multimorbidity is recognized internationally as having a serious
impact on health outcomes. It is associated with reduced quality of life,
increased health care utilization, and future functional decline. Physical
activity is associated with good health and psychological well-being. The aim of
this study was to identify the impact of physical activity and physical function
on the development and worsening of multimorbidity over time. Methods: Using The
Irish Longitudinal Study on Ageing (TILDA), we analyzed 4,823 participants >=50
years with and without multimorbidity. Multimorbidity was defined as the presence
of >=2 chronic conditions. Development of multimorbidity was measured as the
accrual of additional conditions over a 2-year period. Physical activity and
physical function were measured using the International Physical Activity
Questionnaire (IPAQ), gait speed (m/sec), and grip strength (kg). Results:
Sixteen groups of chronic conditions were included in analyses. 53.7% of included
participants had multimorbidity at baseline and 71.7% at follow-up. Six hundred
and thirty-eight of 2,092 (30.4%) participants without multimorbidity and 1,005
of 2,415 (41.6%) with existing multimorbidity developed new condition/s. Gait
speed (relative risk [RR] = 0.67, confidence interval [CI]: 0.49-0.90), grip
strength (RR = 0.98, CI: 0.97-0.99), and age (compared to 50-59 years, 60-69: RR
= 1.30, CI: 1.11-1.52; >=70: RR = 1.35, CI: 1.03-1.77) were significantly
associated with the development of multimorbidity and accrual of additional
conditions. Conclusion: These results show that physical function is associated
with the development and worsening of multimorbidity over time. They support the
recent National Institute for Health & Care Excellence (NICE) Guidance on
multimorbidity that suggests that patients with multimorbidity and reduced gait
speed should be identified and targeted for interventions to improve health
outcomes.
PMID- 29346527
TI - Progesterone effects on extracellular vesicles in the sheep uterus.
AB - Progesterone (P4) acts via the endometrium to promote conceptus growth and
implantation for pregnancy establishment. Many cells release extracellular
vesicles (EVs) that are membrane-bound vesicles of endosomal and plasma membrane
origin. In sheep, endometrial-derived EVs were found to traffic to the conceptus
trophectoderm. Thus, EVs are hypothesized to be an important mode of
intercellular communication by transferring select RNAs, proteins, and lipids
between the endometrium and conceptus. Electron microscopy analysis found that
the endometrial luminal and glandular epithelia were the primary source of EVs in
the uterus of cyclic sheep. Size exclusion chromatography and nanoparticle
tracking analysis (NTA) found that total EV number in the uterine lumen increased
from day 10 to 14 in cyclic sheep. Next, ewes were ovariectomized and hormone
replaced to determine effects of P4 on the endometrium and EVs in the uterine
lumen. Transcriptome analyses found that P4 regulated 1611 genes and nine miRNAs
in the endometrium. Total EV number in the uterine lumen was increased by P4
treatment. Small RNA sequencing of EVs detected expression of 768 miRNAs and
determined that P4 regulated seven of those miRNAs. These studies provide
fundamental new information on how P4 influences endometrial function to regulate
conceptus growth for pregnancy establishment in sheep.
PMID- 29346528
TI - A novel stromal lncRNA signature reprograms fibroblasts to promote the growth of
oral squamous cell carcinoma via LncRNA-CAF/interleukin-33.
AB - Stromal carcinoma-related fibroblasts (CAFs) are the main type of non-immune
cells in the tumor microenvironment (TME). CAFs interact with cancer cells to
promote tumor proliferation. Long non-coding RNAs (lncRNAs) are known to regulate
cell growth, apoptosis and metastasis of cancer cells, but their role in stromal
cells is unclear. Using RNA sequencing, we identified a stromal lncRNA signature
during the transformation of CAFs from normal fibroblasts (NFs) in oral squamous
cell carcinoma (OSCC). We uncovered an uncharacterized lncRNA, FLJ22447, which
was remarkably up-regulated in CAFs, referred to LncRNA-CAF (Lnc-CAF) hereafter.
Interleukin-33 (IL-33) was mainly located in the stroma and positively co
expressed with Lnc-CAF to elevate the expression of CAF markers (alpha-SMA,
vimentin and N-cadherin) in fibroblasts. In a co-culture system, IL-33 knockdown
impaired Lnc-CAF-mediated stromal fibroblast activation, leading to decreased
proliferation of tumor cells. Mechanistically, Lnc-CAF up-regulated IL-33 levels
and prevented p62-dependent autophagy-lysosome degradation of IL-33, which was
independent of LncRNA-protein scaffold effects. Treatment with the autophagy
inducer, rapamycin, impaired the proliferative effect of Lnc-CAF/IL-33 by
promoting IL-33 degradation. In turn, tumor cells further increased Lnc-CAF
levels in stromal fibroblasts via exosomal Lnc-CAF. In patients with OSCC, high
Lnc-CAF/IL-33 expression correlated with high TNM stage (n = 140). Moreover, high
Lnc-CAF expression predicted poor prognosis. In vivo, Lnc-CAF knockdown
restricted tumor growth and was associated with decreased Ki-67 expression and
alpha-SMA+ CAF in the stroma. In conclusion, we identified a stromal lncRNA
signature, which reprograms NFs to CAFs via Lnc-CAF/IL-33 and promotes OSCC
development.
PMID- 29346529
TI - Echocardiographic criteria to detect unicuspid aortic valve morphology.
AB - Aims: Unicuspid aortic valve (UAV) is a rare congenital malformation associated
with severe aortic stenosis or regurgitation. This study aimed to systematically
determine echocardiographic criteria to identify UAV. Methods and results: All
patients underwent a preoperative baseline examination, including
echocardiography. A total of 69 patients with intraoperatively confirmed UAV
underwent an aortic valve repair procedure between August 2001 and May 2011. To
compare the findings of UAV cases with those of other valve morphologies, we
examined 99 consecutive patients with a bicuspid aortic valve (BAV) and 103
consecutive patients with a tricuspid aortic valve (TAV) undergoing isolated
aortic valve surgery before May 2016. The mean age of the 271 patients was 44.2
+/- 12.8 years; 85% were male, with a mean body mass index of 26.2 +/- 4.0 kg/m2.
Patients with UAV were younger and had fewer co-morbidities than patients with
BAV or TAV, respectively. The major criteria for the echocardiographic diagnosis
of UAV were defined based on our preoperative examination as follows: (i) single
commissural attachment zone, (ii) rounded, leaflet-free edge on the opposite side
of the commissural attachment zone, (iii) eccentric valvular orifice during
systole, and (iv) patient age <20 years and mean transvalvular gradient >15 mmHg.
The minor criteria were defined as an associated thoracic aortopathy and age <40
years. Three out of the four major criteria or two out of the four major criteria
and one minor criterion were met in all patients with UAV and in none of the
patients with BAV or TAV. Associated 95% confidence intervals were calculated for
each estimate of sensitivity (94.7-100%) and specificity (98.1-100%), indicating
that an adequate number of patients were included in each of the three groups.
Conclusion: The proposed echocardiographic score appears to be a specific and
sensitive method to distinguish UAV from BAV and TAV.
PMID- 29346530
TI - Bacterioplankton composition in tropical high-elevation lakes of the Andean
plateau.
AB - High-elevation lakes in the tropics are subject to extreme environmental
fluctuations and microbes may harbor a unique genomic repertoire, but their
composition and diversity are largely unknown. Here, we compared the planktonic
bacterial community composition (BCC) and diversity of three tropical lakes
located in the high Andean plateau (>=4400 m above sea level) during the dry and
wet season. Diversity in these lakes was higher in the cool and wet season than
in the warm and dry one. Operational taxonomic units (OTUs) composition was
significantly different among lakes and between seasons. Members of the class
Opitutae, Spartobacteria, Burkholderiales and Actinobacteria were dominant, but
only the hgcI clade (Actinobacteria) and the Comamonadaceae family
(Burkholderiales) were shared between seasons among the three lakes. In general,
a large percentage (up to 42%) of the rare OTUs was unclassified even at the
family level. In one lake, a pycnocline and an anoxic water layer with high
abundance of Thiocapsa sp. was found in the wet season indicating that the known
polymictic thermal condition is not always given. Our study highlights the
particular BCC of tropical high-elevation lakes and also how little is known
about the variability in physico-chemical conditions of these ecosystems.
PMID- 29346531
TI - Doppler assessment of aortic stenosis: a 25-operator study demonstrating why
reading the peak velocity is superior to velocity time integral.
AB - Aims: Measurements with superior reproducibility are useful clinically and
research purposes. Previous reproducibility studies of Doppler assessment of
aortic stenosis (AS) have compared only a pair of observers and have not explored
the mechanism by which disagreement between operators occurs. Using custom
designed software which stored operators' traces, we investigated the
reproducibility of peak and velocity time integral (VTI) measurements across a
much larger group of operators and explored the mechanisms by which disagreement
arose. Methods and results: Twenty-five observers reviewed continuous wave (CW)
aortic valve (AV) and pulsed wave (PW) left ventricular outflow tract (LVOT)
Doppler traces from 20 sequential cases of AS in random order. Each operator
unknowingly measured each peak velocity and VTI twice. VTI tracings were stored
for comparison. Measuring the peak is much more reproducible than VTI for both PW
(coefficient of variation 10.1 vs. 18.0%; P < 0.001) and CW traces (coefficient
of variation 4.0 vs. 10.2%; P < 0.001). VTI is inferior because the steep early
and late parts of the envelope are difficult to trace reproducibly. Dimensionless
index improves reproducibility because operators tended to consistently over-read
or under-read on LVOT and AV traces from the same patient (coefficient of
variation 9.3 vs. 17.1%; P < 0.001). Conclusion: It is far more reproducible to
measure the peak of a Doppler trace than the VTI, a strategy that reduces
measurement variance by approximately six-fold. Peak measurements are superior to
VTI because tracing the steep slopes in the early and late part of the VTI
envelope is difficult to achieve reproducibly.
PMID- 29346532
TI - What color should glacier algae be? An ecological role for red carbon in the
cryosphere.
AB - Red-colored secondary pigments in glacier algae play an adaptive role in melting
snow and ice. We advance this hypothesis using a model of color-based absorption
of irradiance, an experiment with colored particles in snow, and the natural
history of glacier algae. Carotenoids and phenols-astaxanthin in snow-algae and
purpurogallin in ice-algae-shield photosynthetic apparatus by absorbing
overabundant visible wavelengths, then dissipating the excess radiant energy as
heat. This heat melts proximal ice crystals, providing liquid-water in a 0
degrees C environment and freeing up nutrients bound in frozen water. We show
that purple-colored particles transfer 87%-89% of solar energy absorbed by black
particles. However, red-colored particles transfer nearly as much (85%-87%) by
absorbing peak solar wavelengths and reflecting the visible wavelengths most
absorbed by nearby ice and snow crystals; this latter process may reduce
potential cellular overheating when snow insulates cells. Blue and green
particles transfer only 80%-82% of black particle absorption. In the experiment,
red-colored particles melted 87% as much snow as black particles, while blue
particles melted 77%. Green-colored snow-algae naturally occupy saturated snow
where water is non-limiting; red-colored snow-algae occupy drier, water-limited
snow. In addition to increasing melt, we suggest that esterified astaxanthin in
snow-alga cells increases hydrophobicity to remain surficial.
PMID- 29346533
TI - Density of Emerald Ash Borer (Coleoptera: Buprestidae) Adults and Larvae at Three
Stages of the Invasion Wave.
AB - Emerald ash borer (EAB) (Agrilus planipennis Fairmaire) (Coleoptera:
Buprestidae), an invasive phloem-feeding buprestid, has killed hundreds of
millions of ash (Fraxinus spp.) trees in the United States and two Canadian
provinces. We evaluated EAB persistence in post-invasion sites and compared EAB
adult captures and larval densities in 24 forested sites across an east-west
gradient in southern Michigan representing the Core (post-invasion), Crest (high
EAB populations), and Cusp (recently infested areas) of the EAB invasion wave.
Condition of green ash (Fraxinus pennsylvanica Marsh) trees were recorded in
fixed radius plots and linear transects in each site. Ash mortality was highest
in Core sites in the southeast, moderate in Crest sites in central southern
Michigan, and low in Cusp sites in the southwest. Traps and trap trees in Crest
sites accounted for 75 and 60% of all EAB beetles captured in 2010 and 2011,
respectively. Populations of EAB were present in all Core sites and traps in
these sites captured 13% of all beetles each year. Beetle captures and larval
densities at Cusp sites roughly doubled between 2010 and 2011, reflecting the
increasing EAB populations. Sticky bands on girdled trees captured the highest
density of EAB beetles per m2 of area, while baited double-decker traps had the
highest detection rates and captured the most beetles. Larval densities were
higher on girdled ash than on similar ungirdled trees and small planted trees.
Woodpecker predation and a native larval parasitoid were present in all three
invasion regions but had minor effects on ash survival and EAB densities.
PMID- 29346534
TI - Microbial community structure of sea spray aerosols at three California beaches.
AB - We characterized the microbial communities in sea spray aerosols (SSA), water and
sand of three beaches in central California (Cowell Beach, Baker Beach and Lovers
Point) by sequencing the V4 region of the 16S rRNA gene. Average concentrations
of 16S rRNA genes in SSA ranged from 2.4 * 104 to 1.4 * 105 gene copies per m3 of
air. A total of 9781 distinct OTUs were identified in SSA and of these, 1042 OTUs
were found in SSA of all beaches. SSA microbial communities included marine taxa,
as well as some associated with the terrestrial environment. SSA taxa included
organisms that play important roles in biogeochemical cycling of elements such as
Planctomyces and Synechococcus, as well as those representing potential pathogens
and fecal indicator bacteria including Staphylococcus epidermidis and
Enterococcus spp. There were a large number of shared OTUs among SSA and water,
and there was relatively high similarity between SSA and water communities.
Results are consistent with a conceptual model where SSA is generated by breaking
waves and bubble bursting in marine waters and that enables the transport of
microorganisms from the sea to sand or other environments.
PMID- 29346535
TI - Tricuspid regurgitation in acute heart failure: is there any incremental risk?
AB - Aim: Significant tricuspid regurgitation (TR) is common in heart failure (HF) and
portends poor prognosis. We sought to determine whether the poor outcome results
from the TR itself, or whether the TR is a surrogate marker of advanced left
sided myocardial or valvular heart disease. Methods and results: We studied 639
patients admitted for acute HF. The relationship between TR severity and the
endpoint of readmission for HF or mortality was assessed after adjustment for
multiple clinical and echocardiographic parameters. Higher TR grade was
associated with higher congestion score and with other cardiac abnormalities
including reduced left ventricular systolic function, moderate or severe mitral
regurgitation, pulmonary hypertension (PH, defined as pulmonary artery systolic
pressure >= 50 mmHg), and right ventricular dysfunction (all P < 0.001). Only 7%
of patients with moderate or severe TR were free of other cardiac lesions. In
adjusted models, moderate or severe TR was not associated with readmission for HF
or mortality [hazard ratio (HR) 1.24, 95% confidence interval (95% CI) 0.97
1.57]. Patients with moderate/severe TR had similar risk for HF readmission or
death compared with patients with trivial/mild TR when PH was not present (HR
1.17; 95% CI 0.78-1.75, P = 0.40) whereas the risk was higher in moderate/severe
TR and PH (HR 1.78; 95% CI 1.34-2.36, P < 0.0001). Conclusion: Patients
presenting with symptomatic HF and significant TR have multiple coexisting
cardiac abnormalities. TR provides no additive risk in the presence of normal or
mildly elevated pulmonary pressures. However, it is associated with excess
rehospitalizations and mortality in patients with PH.
PMID- 29346536
TI - Residual carcinoma cells after chemoradiotherapy for esophageal squamous cell
carcinoma patients: striving toward appropriate judgment of biopsy.
AB - In esophageal squamous cell carcinoma (ESCC) patients who are treated with
chemoradiotherapy (CRT), identification of the presence or absence of residual or
recurrent carcinoma is usually pivotal in their clinical management. In addition,
the extent of carcinoma invasion into the esophageal wall could determine the
clinical outcome of these patients following CRT. Therefore, in this study, we
evaluated the response to CRT both macroscopically and histologically in a
consecutive series of 42 ESCC patients receiving neoadjuvant chemoradiotherapy
following curative esophageal resection at Tohoku University Hospital between
August 2011 and December 2012. The histological grading of tumor regression was
as follows: grade 3, markedly effective (no viable residual tumor cells); grade
2, moderately effective (residual tumor cells in less than one-third of the
tumor); grade 1, slightly effective (1b, residual tumor cells in one-third to two
thirds of the tumor; 1a, residual tumor cells in more than two-thirds of the
tumor); and grade 0, ineffective. In this study, we selected grade 2 and 1b cases
because they might show a complete response with definitive CRT. We evaluated the
presence of any residual in situ lesions and tumor depth in detail. The grading
of tumor regression in primary sites was as follows: grade 3 (7 cases), grade 2
(16 cases), grade 1b (13 cases), and grade 1a (6 cases). The concordance rate
between macroscopic and histopathological evaluation on the depth of the tumor
was 40% (17/42). Among 29 cases (grade 2 and grade 1b), intraepithelial lesions
were not detected in 17 cases, and tumor nests were not detected in the lamina
propria mucosae in 9 cases. The results of this study highlight the difficulties
of detecting residual carcinoma cells using conventional endoscopic biopsy in
patients who have received CRT. Therefore, when residual cancer is clinically
suspected in patients who have received CRT, the biopsy specimen should be
obtained from the deep layer of the esophagus whenever possible. Additionally,
close follow-up is required using positron emission tomography/computed
tomography, endoscopy, and other radiological evaluations.
PMID- 29346537
TI - Cerebral mitochondrial dysfunction associated with deep hypothermic circulatory
arrest in neonatal swine.
AB - OBJECTIVES: Controversy remains regarding the use of deep hypothermic circulatory
arrest (DHCA) in neonatal cardiac surgery. Alterations in cerebral mitochondrial
bioenergetics are thought to contribute to ischaemia-reperfusion injury in DHCA.
The purpose of this study was to compare cerebral mitochondrial bioenergetics for
DHCA with deep hypothermic continuous perfusion using a neonatal swine model.
METHODS: Twenty-four piglets (mean weight 3.8 kg) were placed on cardiopulmonary
bypass (CPB): 10 underwent 40-min DHCA, following cooling to 18 degrees C, 10
underwent 40 min DHCA and 10 remained at deep hypothermia for 40 min; animals
were subsequently rewarmed to normothermia. 4 remained on normothermic CPB
throughout. Fresh brain tissue was harvested while on CPB and assessed for
mitochondrial respiration and reactive oxygen species generation. Cerebral
microdialysis samples were collected throughout the analysis. RESULTS: DHCA
animals had significantly decreased mitochondrial complex I respiration, maximal
oxidative phosphorylation, respiratory control ratio and significantly increased
mitochondrial reactive oxygen species (P < 0.05 for all). DHCA animals also had
significantly increased cerebral microdialysis indicators of cerebral ischaemia
(lactate/pyruvate ratio) and neuronal death (glycerol) during and after
rewarming. CONCLUSIONS: DHCA is associated with disruption of mitochondrial
bioenergetics compared with deep hypothermic continuous perfusion. Preserving
mitochondrial health may mitigate brain injury in cardiac surgical patients.
Further studies are needed to better understand the mechanisms of neurological
injury in neonatal cardiac surgery and correlate mitochondrial dysfunction with
neurological outcomes.
PMID- 29346538
TI - Vitamin K5 is an efficient photosensitizer for ultraviolet A light inactivation
of bacteria.
AB - Photodynamic treatment combining light and a photosensitizer molecule can be an
effective method to inactivate pathogenic bacteria. This study identified vitamin
K5 as an efficient photosensitizer for ultraviolet light A (UVA)-induced
bacterial inactivation. Six bacterial species, Bacillus cereus (vegetative form),
Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus
epidermidis, Klebsiella pneumoniae, and two species of antibiotic-resistant
bacteria, Pseudomonas aeruginosa* and Staphylococcus aureus*, were suspended in
aqueous solutions with or without vitamin K5 and exposed to UVA irradiation. UVA
irradiation (5.8 J cm-2) with vitamin K5 (1600 MUmol l-1) reduced the colony
forming units (CFU) of these bacteria by three to seven logs. Antibiotic
resistant bacteria were also susceptible to the bactericidal effects of UVA and
vitamin K5 combination treatment. Inactivation of bacteria in human plasma
required higher doses of UVA light and vitamin K5. UVA irradiation (30 J cm-2)
with vitamin K5 (2000 MUmol l-1) reduced E. coli and S. aureus spiked into human
plasma by seven logs CFU/ml. Reactive oxygen species, such as superoxide anion
radicals and hydroxyl radicals, were found to be generated in vitamin K5 aqueous
solution after UVA irradiation, suggesting these oxygen species may mediate the
inactivation of the bacteria.
PMID- 29346539
TI - CORRIGENDUM FOR "Functional Characterization of MicroRNA-27a-3p Expression in
Human Polycystic Ovary Syndrome".
PMID- 29346540
TI - Blood and lymphatic vessels contribute to the impact of the immune
microenvironment on clinical outcome in non-small-cell lung cancer.
AB - OBJECTIVES: Lymphangiogenesis plays a critical role in the immune response,
tumour progression and therapy effectiveness. The aim of this study was to
determine whether the interplay between the lymphatic and the blood
microvasculature, tumour-infiltrating lymphocytes and the programmed death 1 (PD
1)/programmed death ligand 1 (PD-L1) immune checkpoint constitutes an immune
microenvironment affecting the clinical outcome of patients with non-small-cell
lung cancer. METHODS: Samples from 50 squamous cell carcinomas and 42
adenocarcinomas were subjected to immunofluorescence to detect blood and
lymphatic vessels. CD3pos, CD8pos and PD-1pos tumour-infiltrating lymphocytes and
tumour PD-L1 expression were assessed by immunohistochemical analysis. RESULTS:
Quantification of vascular structures documented a peak of lymphatics at the
invasive margin together with a decreasing gradient of blood and lymphatic
vessels from the peritumour area throughout the neoplastic core. Nodal
involvement and pathological stage were strongly associated with vascularization,
and an increased density of vessels was detected in samples with a higher
incidence of tumour-infiltrating lymphocytes and a lower expression of PD-L1.
Patients with a high PD-L1 to PD-1 ratio and vascular rarefaction had a gain of
10 months in overall survival compared to those with a low ratio and prominent
vascularity. CONCLUSIONS: Microvessels are an essential component of the cancer
immune microenvironment. The clinical impact of the PD-1/PD-L1-based immune
contexture may be implemented by the assessment of microvascular density to
potentially identify patients with non-small-cell lung cancer who could benefit
from immunotherapy and antiangiogenic treatment.
PMID- 29346541
TI - Practical implications of erythromycin resistance gene diversity on surveillance
and monitoring of resistance.
AB - Use of antibiotics in human and animal medicine has applied selective pressure
for the global dissemination of antibiotic-resistant bacteria. Therefore, it is
of interest to develop strategies to mitigate the continued amplification and
transmission of resistance genes in environmental reservoirs such as farms,
hospitals and watersheds. However, the efficacy of mitigation strategies is
difficult to evaluate because it is unclear which resistance genes are important
to monitor, and which primers to use to detect those genes. Here, we evaluated
the diversity of one type of macrolide antibiotic resistance gene (erm) in one
type of environment (manure) to determine which primers would be most informative
to use in a mitigation study of that environment. We analyzed all known erm genes
and assessed the ability of previously published erm primers to detect the
diversity. The results showed that all known erm resistance genes group into 66
clusters, and 25 of these clusters (40%) can be targeted with primers found in
the literature. These primers can target 74%-85% of the erm gene diversity in the
manures analyzed.
PMID- 29346542
TI - Hepatitis B in Moroccan-Dutch: a qualitative study into determinants of screening
participation.
AB - Background: Chronic hepatitis B (HBV) leads to an increased risk for liver
cirrhosis and liver cancer. In the Netherlands, chronic HBV prevalence in the
general population is 0.20%, but 3.77% in first generation immigrants. Our aim
was to identify determinants associated with the intention to participate in HBV
testing among first generation Moroccan immigrants, one of the two largest
immigrant groups targeted for screening. Methods: Semi-structured interviews were
held with first (n = 9) and second generation (n = 10) Moroccan-Dutch immigrants,
since second generation immigrants frequently act as their parents' brokers in
healthcare. Results: Most participants had little knowledge about hepatitis B,
but had a positive attitude towards screening. Facilitators for screening
intention were perceived susceptibility to and severity of disease, positive
attitude regarding prevention, wishing to know their hepatitis B status and to
prevent potential hepatitis B transmission to others. Additional cultural
facilitators included fear (of developing cancer), and existing high health care
utilization; a religious facilitator was the responsibility for one's own health
and that of others. Barriers included lack of awareness and knowledge, practical
issues, not having symptoms, negative attitude regarding prevention, fear about
the test result and low-risk perception. A cultural barrier was shame and stigma,
and a religious barrier was fatalism. Conclusion: We identified important
facilitators and barriers, which we found, can be interpreted differently.
Specific and accurate information should be provided, accompanied by strategies
to address shame and stigma, in which Islamic religious leaders could play a role
in bringing information across.
PMID- 29346543
TI - The Impact of Reported Beta-Lactam Allergy in Hospitalized Patients With
Hematologic Malignancies Requiring Antibiotics.
AB - Background: Patients hospitalized with hematologic malignancy are particularly
vulnerable to infection. The impact of reported beta-lactam (BL) allergy in this
population remains unknown. Methods: This was a retrospective cohort study of
adult inpatients with hematologic malignancy admitted at 2 tertiary care
hospitals from 2010 through 2015. The primary outcome was hospital length of stay
(LOS) after administration of the first antibiotic. Secondary outcomes included
readmission, mortality, complications, hospital charges, and antibiotic usage.
Our goal was to define the impact of BL-only allergy (BLOA) label on clinical
outcomes compared to those with no BL allergy (NBLA) in hematologic malignancy
inpatients who required systemic antibiotics. Results: In our cohort (n = 4671),
38.3% had leukemia, 4.9% had Hodgkin lymphoma, 36.1% had non-Hodgkin lymphoma,
and 20.7% had multiple myeloma. Among patients, 35.1% reported antibiotic
allergy, and 14.1% (n = 660) had BLOA (including 9.3% with penicillin-only
allergy and 3.3% cephalosporin-only allergy). Patients with BLOA had longer
median LOS compared to patients with NBLA (11.3 vs 7.6 days, P < .001), which
remained significant after multivariable adjustment. Patients with BLOA also had
significantly worse outcomes in terms of mortality rate at 30 days (7.6% vs 5.3%,
P = .017) and 180 days (15.8% vs 12.2%, P = .013), 30-day readmission rate,
Clostridium difficile rate, hospital charges ($223 046 vs $173 256, P < .001),
antibiotic classes used, and antibiotic duration. Conclusions: In hospitalized
patients with hematologic malignancy, patients with reported BL allergy had worse
clinical outcomes and higher healthcare cost than those without BL allergy label.
PMID- 29346544
TI - So low... so far so good: neurocognitive impact of lowering LDL-C levels with
PCSK9 inhibitors.
PMID- 29346546
TI - Identifying cardiac pathologies with coronary wave intensity analysis: an
enrichment to the ever-expanding coronary haemodynamics armamentarium?
PMID- 29346545
TI - Influence of Nicotine Metabolism Ratio on [11C]-(+)-PHNO PET Binding in Tobacco
Smokers.
AB - Background: Identifying the biological basis of smoking cessation success is of
growing interest. The rate of nicotine metabolism, measured by the nicotine
metabolite ratio, affects multiple aspects of nicotine dependence. Fast nicotine
metabolizers tend to smoke more, experience more withdrawal and craving, and have
lower cessation rates compared with slow metabolizers. The nicotine metabolite
ratio predicts treatment response, and differences in brain activation between
fast metabolizers and slow metabolizers have been reported in fMRI studies. As
reinforcing/rewarding effects of tobacco are associated with dopamine
transmission, the purpose of the present study was to study the dopaminergic
system in human smokers based on their nicotine metabolite ratio. Methods: The
first aim of the study was to explore if there were differences in D2 and D3
receptor binding between fast metabolizers and slow metabolizers during
abstinence. The second aim was to explore smoking-induced dopamine release in
both groups. Participants underwent 2 [11C]-(+)-PHNO PET scans: one scan during
abstinence and the other after smoking a tobacco cigarette. Subjective measures
were recorded and blood was drawn for measurement of nicotine and cotinine
levels. Results: During abstinence, slow metabolizers (n = 13) had lower [11C]
(+)-PHNO binding potential than fast metabolizers (n = 15) restricted to the D2
regions of the associative striatum and sensorimotor striatum. After smoking a
cigarette, [11C]-(+)-PHNO binding potential was decreased in the limbic striatum
and ventral pallidum, suggestive of increases in dopamine, but there were no
nicotine metabolite ratio differences. Conclusions: Further studies are required
to delineate if differences in [11C]-(+)-PHNO binding between slow metabolizers
and fast metabolizers at abstinence baseline are preexisting traits or induced by
prolonged tobacco use.
PMID- 29346548
TI - Impact of the EURO-2016 football cup on emergency department visits related to
alcohol and injury.
AB - In Marseille, the 2016 EURO football cup days were independently associated with
a 43% increase in alcohol-related visits in the Emergency Department (ED).
Patients admitted for alcohol consumption were younger (41 vs. 46.6; P < 0.001),
more often male (82.8% vs. 60.1%; P < 0.001) and more often admitted as
inpatients (24.0% vs. 16.5%; P = 0.03) than those admitted for injury. Unlike
reported in previous studies, injury-related visits did not increase. This could
be explained by coding practice variability between EDs (alcohol or injury). To
account for this variability, both diagnosis groups must be separately included
when using ED data for preparing and monitoring major gatherings.
PMID- 29346547
TI - How to do (or not to do) ... a health financing incidence analysis.
AB - Financing incidence analysis (FIA) assesses how the burden of health financing is
distributed in relation to household ability to pay (ATP). In a progressive
financing system, poorer households contribute a smaller proportion of their ATP
to finance health services compared to richer households. A system is regressive
when the poor contribute proportionately more. Equitable health financing is
often associated with progressivity. To conduct a comprehensive FIA, detailed
household survey data containing reliable information on both a cardinal measure
of household ATP and variables for extracting contributions to health services
via taxes, health insurance and out-of-pocket (OOP) payments are required.
Further, data on health financing mix are needed to assess overall FIA. Two major
approaches to conducting FIA described in this article include the structural
progressivity approach that assesses how the share of ATP (e.g. income) spent on
health services varies by quantiles, and the effective progressivity approach
that uses indices of progressivity such as the Kakwani index. This article
provides some detailed practical steps for analysts to conduct FIA. This includes
the data requirements, data sources, how to extract or estimate health payments
from survey data and the methods for assessing FIA. It also discusses data
deficiencies that are common in many low- and middle-income countries (LMICs).
The results of FIA are useful in designing policies to achieve an equitable
health system.
PMID- 29346550
TI - Coronary microvascular dysfunction and heart failure with preserved ejection
fraction as female-pattern cardiovascular disease: the chicken or the egg?
PMID- 29346549
TI - Transcriptome and functional analysis in a Drosophila model of NGLY1 deficiency
provides insight into therapeutic approaches.
AB - Autosomal recessive loss-of-function mutations in N-glycanase 1 (NGLY1) cause
NGLY1 deficiency, the only known human disease of deglycosylation. Patients
present with developmental delay, movement disorder, seizures, liver dysfunction
and alacrima. NGLY1 is a conserved cytoplasmic component of the Endoplasmic
Reticulum Associated Degradation (ERAD) pathway. ERAD clears misfolded proteins
from the ER lumen. However, it is unclear how loss of NGLY1 function impacts ERAD
and other cellular processes and results in the constellation of problems
associated with NGLY1 deficiency. To understand how loss of NGLY1 contributes to
disease, we developed a Drosophila model of NGLY1 deficiency. Loss of NGLY1
function resulted in developmental delay and lethality. We used RNAseq to
determine which processes are misregulated in the absence of NGLY1. Transcriptome
analysis showed no evidence of ER stress upon NGLY1 knockdown. However, loss of
NGLY1 resulted in a strong signature of NRF1 dysfunction among downregulated
genes, as evidenced by an enrichment of genes encoding proteasome components and
proteins involved in oxidation-reduction. A number of transcriptome changes also
suggested potential therapeutic interventions, including dysregulation of GlcNAc
synthesis and upregulation of the heat shock response. We show that increasing
the function of both pathways rescues lethality. Together, transcriptome analysis
in a Drosophila model of NGLY1 deficiency provides insight into potential
therapeutic approaches.
PMID- 29346551
TI - Brazil's Family Health Strategy: factors associated with programme uptake and
coverage expansion over 15 years (1998-2012).
AB - Universal Health Coverage (UHC) is one of the United Nations Sustainable
Development Goals (SDGs). Achieving UHC will require strong health systems to
promote and deliver equitable and integrated healthcare services through primary
healthcare (PHC). In Brazil, the Family Health Strategy (FHS) delivers PHC
through the public health system. Created in 1994, the FHS covered almost 123
million individuals (63% of the Brazilian population) by 2015. The FHS has been
associated with many health improvements, but gaps in coverage still remain. This
article examines factors associated with the implementation and expansion of the
FHS across 5419 Brazilian municipalities from 1998 to 2012. The proportion of the
municipal population covered by the FHS over time was assessed using a
longitudinal multilevel model for change that accounted for variables covering
eight domains: economic development, healthcare supply, healthcare needs/access,
availability of other sources of healthcare, political context, geographical
isolation, regional characteristics and population size. Data were obtained from
multiple publicly available sources. During the 15-year study period, national
coverage of the FHS increased from 4.4% to 54%, with 58% of the municipalities
having population coverage of 95% or more, and municipalities that had not
adopted the programme decreased from 86.4% to 4.9%. The increase in FHS uptake
and coverage was not homogenous across municipalities, and was positively
associated with small population size, low population density, low coverage of
private health insurance, low level of economic development, alignment of the
political party of the Mayor and the state Governor, and availability of
healthcare supply. Efforts to expand the FHS coverage will need to focus on
increasing the availability of health personnel, devising financial incentives
for municipalities to uptake/expand the FHS and devising new policies that
encompass both private and public sectors.
PMID- 29346552
TI - Safety profile of near-zero fluoroscopy atrial fibrillation ablation with non
fluoroscopic catheter visualization: experience from 1000 consecutive procedures.
AB - Aims: Efforts to reduce radiation exposure during catheter ablation procedures
have included the use of various technological measures. Significant results have
been achieved to the point where near lead-free procedures in routine clinical
practice has become a realistic goal. The integration of MediGuide technology
[non-fluoroscopic catheter visualization technology (NFCV)] and three-dimensional
electroanatomical mapping is one of the methods developed in response to
radiation reduction initiatives. We aimed to evaluate the impact of this NFCV
technology on atrial fibrillation (AF) catheter ablation in terms of reduction in
procedural and radiation time as well as safety aspects. Methods and results:
Between March 2012 and March 2017, a total of 1000 patients underwent AF ablation
using NFCV. Patient and procedural data and complications within the first 3
months were entered into a prospective registry and analysed. We assessed
procedure time, fluoroscopy time, and dose and complications. In a cohort of 1000
patients (62.9 +/- 11 years; 72% men; left ventricular ejection fraction 57%; and
left atrial diameter 43.2 mm), the median procedure time was 120 min, median
fluoroscopy time was 0.90 min, and the median fluoroscopy dose of was 345.1 cGy .
cm2. Stratification of the first (Group 1) and the last 250 (Group 2) cases
showed significant improvement in the median procedure time (140-110 min) and
reduction in the median fluoroscopy time (6-0.5 min) and the median dose (2263
151.9 cGy . cm2). The overall complication rate was 2.0%. Conclusion: The use of
NFCV technology enables safe, consistent, and 'near lead-free' performance of AF
ablation in routine clinical practice.
PMID- 29346553
TI - Prediction of Barrett's esophagus: are we there yet?
PMID- 29346554
TI - Functional Roles of Sex-Biased, Growth Hormone-Regulated MicroRNAs miR-1948 and
miR-802 in Young Adult Mouse Liver.
AB - Sex-specific temporal patterns of pituitary growth hormone (GH) secretion
determine the sex-biased transcription of hundreds of genes in the liver and
impart important sex differences in liver physiology, metabolism, and disease.
Sex differences in hepatic gene expression vary widely, ranging from less than
twofold to >1000-fold in the mouse. Here, we use small RNA sequencing to discover
24 sex-biased mouse liver microRNAs (miRNAs), and then investigate the roles of
two of these miRNAs in GH-regulated liver sex differences. Studies in prepubertal
and young adult mice, and in mice in which pituitary hormones are ablated or
where sex-specific hepatic GH signaling is dysregulated, demonstrated that the
male-biased miR-1948 and the female-biased miR-802 are both regulated by sex
specific pituitary GH secretory patterns, acquire sex specificity at puberty, and
are dependent on the GH-activated transcription factor STAT5 for their sex
specific expression. Both miRNAs are within genomic regions characterized by sex
biased chromatin accessibility. miR-1948, an uncharacterized miRNA, has essential
features for correct Drosha/Dicer processing, generates a bona fide mature miRNA
with strong strand bias for the 5p arm, and is bound by Argonaute in liver
tissue, as is miR-802. In vivo studies using inhibitory locked nucleic acid
sequences revealed that miR-1948-5p preferentially represses female-biased
messenger RNAs (mRNAs) and induces male-biased mRNAs in male liver; conversely,
miR-802-5p preferentially represses male-biased mRNAs and increases levels of
female-biased mRNAs in female liver. Cytochrome P450 mRNAs were strongly enriched
as targets of both miRNAs. Thus, miR-1948-5p and miR-802-5p are functional
components of the GH regulatory network that shapes sex-differential gene
expression in mouse liver.
PMID- 29346557
TI - Peer supporters' experiences on an Australian perinatal mental health helpline.
AB - Perinatal mental health is an important public health issue, and peer support is
a potentially important strategy for emotional well-being in the perinatal
period. PANDA Perinatal Anxiety & Depression Australia provides support to
individuals impacted by perinatal mental health issues via the National Perinatal
Anxiety & Depression Helpline. Callers receive peer support from volunteers and
counselling from paid professional staff. The views and experiences of PANDA peer
support volunteers have not previously been studied. We conducted two focus
groups and an online survey to explore the experiences of women providing
volunteer peer support on the Helpline. Data collection took place in October and
November 2013. Two social theories were used in framing and addressing the study
aims and in interpreting our findings: the Empathy-Altruism Hypothesis, and the
Helper Therapy Principle. All PANDA volunteers were invited to participate (n =
40). Eight volunteers attended a focus group, and 11 survey responses were
received. Descriptive statistics were used to analyse quantitative data. All
survey respondents 'strongly agreed' that they felt positive about being part of
PANDA. Thematic analysis of data from focus groups and open-ended survey
responses identified the following themes: motivated to help others, supported to
support callers, helping to make a difference and emotional impacts for
volunteers. Respondents described a strong desire to support others experiencing
emotional distress as a motivator to volunteer. Although perinatal peer support
services are designed to benefit those who receive support, this study suggests
volunteers may also experience personal benefits from the role.
PMID- 29346556
TI - Cohort Profile: The Epidemiology of Chronic Diseases and Multimorbidity. The
EpiChron Cohort Study.
PMID- 29346555
TI - Data Resource Profile: Expansion of the Rochester Epidemiology Project medical
records-linkage system (E-REP).
PMID- 29346558
TI - Thoraco-abdominal aortic aneurysm rupture in a patient with Shprintzen-Goldberg
syndrome.
AB - Shprintzen-Goldberg syndrome is a rare systemic connective tissue disorder
characterized by craniosynostosis, skeletal abnormalities, infantile hypotonia,
mild-to-moderate intellectual disability and cardiovascular anomalies. To our
knowledge, this is the first report of a Shprintzen-Goldberg syndrome patient who
developed a thoraco-abdominal aortic aneurysm. The aneurysm grew rapidly
necessitating emergent thoraco-abdominal aortic replacement. The postoperative
course was uneventful, and a careful lifetime follow-up was planned.
PMID- 29346560
TI - Aggregation and travelling wave dynamics in a two-population model of cancer cell
growth and invasion.
AB - Cells adhere to each other and to the extracellular matrix (ECM) through protein
molecules on the surface of the cells. The breaking and forming of adhesive
bonds, a process critical in cancer invasion and metastasis, can be influenced by
the mutation of cancer cells. In this paper, we develop a nonlocal mathematical
model describing cancer cell invasion and movement as a result of integrin
controlled cell-cell adhesion and cell-matrix adhesion, for two cancer cell
populations with different levels of mutation. The partial differential equations
for cell dynamics are coupled with ordinary differential equations describing the
ECM degradation and the production and decay of integrins. We use this model to
investigate the role of cancer mutation on the possibility of cancer clonal
competition with alternating dominance, or even competitive exclusion (phenomena
observed experimentally). We discuss different possible cell aggregation
patterns, as well as travelling wave patterns. In regard to the travelling waves,
we investigate the effect of cancer mutation rate on the speed of cancer
invasion.
PMID- 29346561
TI - Floricolin C elicits intracellular reactive oxygen species accumulation and
disrupts mitochondria to exert fungicidal action.
AB - Candida albicans, one of the most prevalent fungal pathogens, causes severe
mucosal and invasive infections in predisposed individuals. The rise of fungal
infection and drug resistance demands the development of novel antifungal agents.
In this study, we observed that floricolin C (FC), a p-terphenyl pigment from an
endolichenic fungus, killed C. albicans cells in the planktonic state or within
biofilms through reactive oxygen species (ROS) accumulation. Further tests
revealed that FC could directly damage the mitochondria to cause ROS
accumulation. In addition, FC can quench thiol-based agents through a Michael
reaction involving the alpha,beta-unsaturated carbonyl group, whose effect may
chelate intracellular thiol-based molecules or proteins in C. albicans, resulting
in an imbalance in redox homeostasis. Increased ROS generation led to
mitochondrial dysfunction, nuclear dispersion and consequently cell death. We
further demonstrated that FC could prevent biofilm formation of other Candida
species and eradicate their pre-formed biofilms. An in vivo study demonstrated
that FC prolonged the survival of C. albicans-infected Caenorhabditis elegans.
Taken together, our study provides the basis for the application of FC to combat
Candida infections.
PMID- 29346559
TI - Predicting plant biomass accumulation from image-derived parameters.
AB - Background: Image-based high-throughput phenotyping technologies have been
rapidly developed in plant science recently, and they provide a great potential
to gain more valuable information than traditionally destructive methods.
Predicting plant biomass is regarded as a key purpose for plant breeders and
ecologists. However, it is a great challenge to find a predictive biomass model
across experiments. Results: In the present study, we constructed 4 predictive
models to examine the quantitative relationship between image-based features and
plant biomass accumulation. Our methodology has been applied to 3 consecutive
barley (Hordeum vulgare) experiments with control and stress treatments. The
results proved that plant biomass can be accurately predicted from image-based
parameters using a random forest model. The high prediction accuracy based on
this model will contribute to relieving the phenotyping bottleneck in biomass
measurement in breeding applications. The prediction performance is still
relatively high across experiments under similar conditions. The relative
contribution of individual features for predicting biomass was further
quantified, revealing new insights into the phenotypic determinants of the plant
biomass outcome. Furthermore, methods could also be used to determine the most
important image-based features related to plant biomass accumulation, which would
be promising for subsequent genetic mapping to uncover the genetic basis of
biomass. Conclusions: We have developed quantitative models to accurately predict
plant biomass accumulation from image data. We anticipate that the analysis
results will be useful to advance our views of the phenotypic determinants of
plant biomass outcome, and the statistical methods can be broadly used for other
plant species.
PMID- 29346562
TI - Scaffold-free trachea regeneration by tissue engineering with bio-3D printing.
AB - OBJECTIVES: Currently, most of the artificial airway organs still require
scaffolds; however, such scaffolds exhibit several limitations. Alternatively,
the use of an autologous artificial trachea without foreign materials and
immunosuppressants may solve these issues and constitute a preferred tool. The
rationale of this study was to develop a new scaffold-free approach for an
artificial trachea using bio-3D printing technology. Here, we assessed the
circumferential tracheal replacement using scaffold-free trachea-like grafts
generated from isolated cells in an inbred animal model. METHODS: Chondrocytes
and mesenchymal stem cells were isolated from F344 rats. Rat lung microvessel
endothelial cells were purchased. Our bio-3D printer generates spheroids
consisting of several types of cells to create 3D structures. The bio-3D-printed
artificial trachea from spheroids was matured in a bioreactor and transplanted
into F344 rats as a tracheal graft under general anaesthesia. The mechanical
strength of the artificial trachea was measured, and histological and
immunohistochemical examinations were performed. RESULTS: Tracheal
transplantation was performed in 9 rats, which were followed up postoperatively
for 23 days. The average tensile strength of artificial tracheas before
transplantation was 526.3 +/- 125.7 mN. The bio-3D-printed scaffold-free
artificial trachea had sufficient strength to transplant into the trachea with
silicone stents that were used to prevent collapse of the artificial trachea and
to support the graft until sufficient blood supply was obtained. Chondrogenesis
and vasculogenesis were observed histologically. CONCLUSIONS: The scaffold-free
isogenic artificial tracheas produced by a bio-3D printer could be utilized as
tracheal grafts in rats.
PMID- 29346564
TI - Genome-wide comparison of allele-specific gene expression between African and
European populations.
AB - Transcriptomic diversity across human populations reflects differential
regulatory mechanisms. Allelic-imbalanced gene expression is a genetic regulatory
mechanism that contributes to human phenotypic variation. To systematically
investigate genome-wide allele-specific expression (ASE), we analyzed RNA-Seq
data from European and African populations provided by the Geuvadis project. We
identified 11 sites in 8 genes showing ASE in both Europeans and Africans, and 9
sites in 9 genes showing population-specific ASE, including both novel and known
ASE signals. Notably, the top signal of differentiated ASE between inter
continental populations was observed in DNAJC15, of which the derived allele of
rs12015, a single nucleotide polymorphism (SNP), showed significantly higher
expression than did the ancestral allele specifically in European individuals. We
identified a unique haplotype of DNAJC15, where a few SNPs highly differentiated
between European and African populations were strongly linked to sites with high
ASE. Among these, SNP rs17553284 affected the binding of several transcription
factors as well as the genotype-dependent expression of DNAJC15. Therefore, we
speculated that rs17553284 could be a regulatory causal variant that mediates the
ASE of rs12015. We found several variations in ASE between intercontinental
populations. The highly differentiated ASE genes identified here may implicate in
the phenotypic variations among populations that are both evolutionarily and
medically important.
PMID- 29346563
TI - LC3 Immunostaining in the Inferior Olivary Nuclei of Cats With Niemann-Pick
Disease Type C1 Is Associated With Patterned Purkinje Cell Loss.
AB - The feline model of Niemann-Pick disease, type C1 (NPC1) recapitulates the
clinical, neuropathological, and biochemical abnormalities present in children
with NPC1. The hallmarks of disease are the lysosomal storage of unesterified
cholesterol and multiple sphingolipids in neurons, and the spatial and temporal
distribution of Purkinje cell death. In feline NPC1 brain, microtubule-associated
protein 1 light chain 3 (LC3) accumulations, indicating autophagosomes, were
found within axons and presynaptic terminals. High densities of accumulated LC3
were seen in subdivisions of the inferior olive, which project to cerebellar
regions that show the most Purkinje cell loss, suggesting that autophagic
abnormalities in specific climbing fibers may contribute to the spatial pattern
of Purkinje cell loss seen. Biweekly intrathecal administration of 2
hydroxypropyl-beta cyclodextrin (HPbetaCD) ameliorated neurological dysfunction,
reduced cholesterol and sphingolipid accumulation, and increased lifespan in NPC1
cats. LC3 pathology was reduced in treated animals suggesting that HPbetaCD
administration also ameliorates autophagic abnormalities. This study is the first
to (i) identify specific brain regions exhibiting autophagic abnormalities in any
species with NPC1, (ii) provide evidence of differential vulnerability among
discrete brain nuclei and pathways, and (iii) show the amelioration of these
abnormalities in NPC1 cats treated with HPbetaCD.
PMID- 29346565
TI - Apigenin induces cell shrinkage in Candida albicans by membrane perturbation.
AB - Apigenin, a natural flavone, has been well characterized for its their
anticarcinogenic property; however, its bioactivity against pathogenic fungi has
not been investigated in detail. In this study, we examined the antifungal
activity and mode of action of apigenin. Apigenin inhibited the growth of fungal
pathogens, which induced superficial infection and reduced biofilm mass. Three
dimensional flow cytometric analysis demonstrated that apigenin induced
morphological changes, especially cell shrinkage, in Candida albicans. We
investigated the cause of cell shrinkage using the cyanine dye 3,3?
dipropylthiacarbocyanine iodide. Results revealed that apigenin altered the cell
membrane potential. Apigenin also induced membrane dysfunction, and increased
cell permeability to 1,6-diphenyl-1,3,5-hexatriene and propidium iodide. We
observed the influx and efflux of fluorescent molecules of varying molecular
weights and radii across large unilamellar vesicles and live cells that had been
treated with apigenin. Membrane disruption facilitates the release of small
intracellular constituents such as ions and sugars, but not proteins. These
findings suggested that apigenin exerted an antifungal activity by inducing
membrane disturbances, which led to cell shrinkage and leakage of intracellular
components.
PMID- 29346566
TI - A genome-wide association study identifies nucleotide variants at SIGLEC5 and
DEFA1A3 as risk loci for periodontitis.
PMID- 29346567
TI - Epithelial grafting of a decellularized whole-tracheal segment: an in vivo
experimental model.
AB - OBJECTIVES: Prerequisites for successful trachea transplantation include the use
of a biocompatible construct, submucosal vascularization and an epithelial
covering. Implantation of non-epithelialized tracheal scaffolds may lead to
stenosis. However, epithelial grafting or seeding can only be attempted onto a
well-vascularized submucosal bed. Our aim was to investigate a method to prevent
stenosis during prelamination of non-epithelialized, gently decellularized rabbit
tracheae and to evaluate whether grafting of revascularized constructs with
buccal mucosa is feasible. METHODS: Allotracheae underwent two 48-h cycles of
detergent-enzymatic decellularization using sodium deoxycholate and DNAse. In the
first series, 12 circular scaffolds were implanted bilaterally in lateral
thoracic artery flaps (n = 6 rabbits). Right-sided transplants were covered
internally with IntegraTM. In the second series, 10 decellularized tracheae
covered with Integra were prelaminated in flaps (n = 10 rabbits). Twenty-one days
after implantation, revascularized tracheae were grafted with buccal mucosa. A
macroscopic, histological analysis and immunohistochemistry were performed on
explants. RESULTS: In the first series, tracheae without Integra covering
developed significantly greater intraluminal (P = 0.032) and subepithelial
narrowing (P = 0.0345) compared with tracheae with Integra covering. All tracheae
exhibited insufficient submucosal revascularization. In the second series,
submucosal revascularization was incomplete in the first 2 constructs, which were
implanted circularly. These tracheae only showed marginal buccal graft ingrowth.
To accelerate revascularization, the subsequent 8 transplants were opened
longitudinally before implantation. Compared to circularly implanted tracheae,
submucosal revascularization of these transplants was superior (P = 0.0008).
Graft adherence was complete in 6 opened constructs. Mild lymphocytic
infiltration within the buccal graft was detected in 5 specimens. CONCLUSIONS: We
observed satisfactory host integration of opened tracheae that were temporarily
covered with Integra during revascularization and subsequently grafted with
buccal mucosa. Integra successfully prevented stenosis during revascularization.
This model may provide an example of an immunosuppressive-free approach in the
treatment of long-segment tracheal lesions. With the aid of further refinements
such as a respiratory epithelial lining, an orthotopically transplantable
construct could be created.
PMID- 29346568
TI - Are infection specialists recommending short antibiotic treatment durations? An
ESCMID international cross-sectional survey.
AB - Objectives: To evaluate the current practice and the willingness to shorten the
duration of antibiotic therapy among infection specialists. Methods: Infection
specialists giving at least weekly advice on antibiotic prescriptions were
invited to participate in an online cross-sectional survey between September and
December 2016. The questionnaire included 15 clinical vignettes corresponding to
common clinical cases with favourable outcomes; part A asked about the antibiotic
treatment duration they would usually advise to prescribers and part B asked
about the shortest duration they were willing to recommend. Results: We included
866 participants, mostly clinical microbiologists (22.8%, 197/863) or infectious
diseases specialists (58.7%, 507/863), members of an antibiotic stewardship team
in 73% (624/854) of the cases, coming from 58 countries on all continents. Thirty
six percent of participants (271/749) already advised short durations of
antibiotic therapy (compared with the literature) to prescribers for more than
half of the vignettes and 47% (312/662) chose shorter durations in part B
compared with part A for more than half of the vignettes. Twenty-two percent
(192/861) of the participants declared that their regional/national guidelines
expressed durations of antibiotic therapy for a specific clinical situation as a
fixed duration as opposed to a range and in the multivariable analysis this was
associated with respondents advising short durations for more than half of the
vignettes (adjusted OR 1.5, P = 0.02). Conclusions: The majority of infection
specialists currently do not advise the shortest possible duration of antibiotic
therapy to prescribers. Promoting short durations among these experts is urgently
needed.
PMID- 29346570
TI - Implementation status of morbidity and mortality conferences in Swiss hospitals:
a national cross-sectional survey study.
AB - Objective: To determine the implementation status and current practice of
morbidity and mortality conferences (M&MCs) in Switzerland. Design: A national
cross-sectional online survey was conducted in spring 2017. The questionnaire
focused on overall goals, structure and procedures of hospital M&MCs. Further
topics included satisfaction, perceived effectiveness and support requirements.
Setting: A total of 913 chief physicians of surgery and internal medicine, and
specialist fields of obstetrics and gynaecology, anaesthesiology and intensive
care from Swiss acute care hospitals were invited to the survey. 321 completed
the questionnaire, resulting in a 35.2% response rate. Participants: Chief or
senior physicians in charge of the M&MCs in their department. Intervention: No
intervention. Main Outcome Measures: Numbers and percentages of M&MCs within the
surveyed disciplines fulfilling certain characteristics and procedural features.
Results: Among 321 respondents, the majority are conducting M&MCs in their
departments. Within and between the medical disciplines considerable
heterogeneity was found in structural and procedural features of M&MCs. Only a
small part of the reported M&MCs is following a systematic approach and meeting
recommended procedural features. Although the respondents are satisfied and
perceive the M&MCs as an efficient tool, they agree that there is a need for
professionalization and standardization. Conclusion: M&MCs are widely used to
promote medical education, patient safety and quality improvements. However, the
term M&MC seems to cover different types of meetings. Although the overall goals
are similar, various types of M&MCs are used in practice and different objectives
are pursued. Tools such as checklists, guidelines and templates are considered
helpful.
PMID- 29346569
TI - Controlled Antenatal Thyroid Screening II: Effect of Treating Maternal Suboptimal
Thyroid Function on Child Cognition.
AB - Context and Objective: The Controlled Antenatal Thyroid Screening (CATS) study
investigated treatment of suboptimal gestational thyroid function (SGTF) on
childhood cognition and found no difference in intelligence quotient (IQ) at 3
years between children of treated and untreated SGTF mothers. We have measured IQ
in the same children at age 9.5 years and included children from normal
gestational thyroid function (normal-GTF) mothers. Design, Setting, and
Participants: One examiner, blinded to participant group, assessed children's IQ
(Wechsler Intelligence Scale for Children, Fourth Edition UK), long-term memory,
and motor function (Developmental Neuropsychological Assessment II) from children
of 119 treated and 98 untreated SGTF mothers plus children of 232 mothers with
normal-GTF. Logistic regression explored the odds and percentages of an IQ < 85
in the groups. Results: There was no difference in IQ < 85 between children of
mothers with normal-GTF and combined SGTF, i.e., treated and untreated (fully
adjusted odds ratio [OR] = 1.15 [95% confidence interval (CI) 0.52, 2.51]; P =
0.731). Furthermore, there was no significant effect of treatment [untreated OR =
1.33 (95% CI 0.53, 3.34); treated OR = 0.75 (95% CI 0.27, 2.06) P = 0.576]. IQ <
85 was 6.03% in normal-GTF, 7.56% in treated, and 11.22% in untreated groups.
Analyses accounting for treated-SGTF women with free thyroxine > 97.5th
percentile of the entire CATS-I cohort revealed no significant effect on a
child's IQ < 85 in CATS-II. IQ at age 3 predicted IQ at age 9.5 (P < 0.0001) and
accounted for 45% of the variation. Conclusions: Maternal thyroxine during
pregnancy did not improve child cognition at age 9.5 years. Our findings
confirmed CATS-I and suggest that the lack of treatment effect may be a result of
the similar proportion of IQ < 85 in children of women with normal-GTF and SGTF.
PMID- 29346571
TI - Natural Course of Human T-Cell Leukemia Virus Type 1 Proviral DNA Levels in
Carriers During Pregnancy.
AB - The measurement of human T-cell leukemia virus type 1 (HTLV-1) proviral DNA
levels by using polymerase chain reaction has been beneficial for confirming HTLV
1 infection during pregnancy. However, the influence of pregnancy on HTLV-1
infection and proviral DNA levels among pregnant women with HTLV-1 has not been
clarified. We prospectively gathered blood samples from 36 pregnant women in whom
HTLV-1 carriage was previously diagnosed and sequentially measured their proviral
DNA levels. The HTLV-1 proviral DNA levels remained at a plateau during pregnancy
but were elevated after delivery. Moreover, flow cytometry and serological
analyses revealed that the regulatory T-cell population and soluble interleukin 2
receptor levels were similarly elevated after birth in comparison with those in
control pregnant women. This study is the first to provide data on sequential
changes in HTLV-1 proviral DNA levels during and after pregnancy. These findings
will guide the establishment of a better program to prevent mother-to-child
transmission of HTLV-1.
PMID- 29346572
TI - Analysis of experience-regulated transcriptome and imprintome during critical
periods of mouse visual system development reveals spatiotemporal dynamics.
AB - Visual system development is light-experience dependent, which strongly
implicates epigenetic mechanisms in light-regulated maturation. Among many
epigenetic processes, genomic imprinting is an epigenetic mechanism through which
monoallelic gene expression occurs in a parent-of-origin-specific manner. It is
unknown if genomic imprinting contributes to visual system development. We
profiled the transcriptome and imprintome during critical periods of mouse visual
system development under normal- and dark-rearing conditions using B6/CAST F1
hybrid mice. We identified experience-regulated, isoform-specific and brain
region-specific imprinted genes. We also found imprinted microRNAs were
predominantly clustered into the Dlk1-Dio3 imprinted locus with light experience
affecting some imprinted miRNA expression. Our findings provide the first
comprehensive analysis of light-experience regulation of the transcriptome and
imprintome during critical periods of visual system development. Our results may
contribute to therapeutic strategies for visual impairments and circadian rhythm
disorders resulting from a dysfunctional imprintome.
PMID- 29346573
TI - The Addition of Bevacizumab to Oxaliplatin-Based Chemotherapy: Impact Upon
Hepatic Sinusoidal Injury and Thrombocytopenia.
AB - Background: Oxaliplatin-based chemotherapy can cause hepatic sinusoidal injury
(HSI), portal hypertension, and splenic sequestration of platelets. Evidence
suggests that bevacizumab may protect against HSI. Methods: Two cohorts of
metastatic colorectal cancer (CRC) were analyzed: a nonrandomized exploratory
cohort of 184 patients treated at a single institution from 2003 to 2010 and a
confirmatory cohort of 200 patients from a multi-institutional randomized trial
(NO16966). All patients were treated with frontline fluoropyrimidine and
oxaliplatin with or without bevacizumab. Changes in splenic volumes and platelet
counts were compared by treatment, two-sided log-rank test. Results: In the
exploratory cohort, the bevacizumab-treated patients (n = 138) compared with the
nonbevacizumab-treated patients (n = 46) demonstrated a longer median time to
splenic enlargement (>=30%, P = .02) and reduced rate of thrombocytopenia (<150
000/mm3, P = .04). In the confirmatory cohort (106 bevacizumab arm and 94 placebo
arm), the median time to a spleen enlargement of 30% or more was 7.6 vs 5.4 (P =
.01), and six-month cumulative incidence of thrombocytopenia (platelets < 100
000/mm3) was 19% vs 51% (P < .001) for bevacizumab compared with placebo. The
development of an increasing spleen size was associated with the risk of either
grade 1 or grade 2 thrombocytopenia (P < .001). The cumulative rate of grade 1 or
grade 2 thrombocytopenia was statistically less in the bevacizumab arm, with six
month grade 2 thrombocytopenia rates of 4% vs 23% (P < .001). Patients with a
large spleen prior to chemotherapy initiation appeared to be at highest risk of
this toxicity. Conclusion: In metastatic CRC, the addition of bevacizumab to
oxaliplatin-based chemotherapy reduces the frequency of splenic enlargement and
the rate of thrombocytopenia.
PMID- 29346574
TI - Systematic genetic interaction studies identify histone demethylase Utx as
potential target for ameliorating Huntington's disease.
PMID- 29346575
TI - Abacavir Induces Arterial Thrombosis in a Murine Model.
AB - Background: The purinergic system is known to underlie prothrombotic and
proinflammatory vascular programs, making the profile of experimental actions
demonstrated by abacavir compatible with thrombogenesis. However, direct evidence
of a prothrombotic effect by the drug has been lacking. Methods: The present
study appraised the effects of abacavir in a well-validated animal model of
arterial thrombosis. The role of ATP-P2X7 receptors in the actions of the drug
was also assessed, and the actions of recognized vascular-damaging agents and
other nucleoside reverse-transcriptase inhibitors (NRTIs) were evaluated and
compared to those of abacavir. Results: Abacavir dose-dependently promoted
thrombus formation. This effect was reversed by a P2X7-receptor antagonist and
was nonexistent in P2X7 knockout mice. The effects of abacavir were similar to
those of diclofenac and rofecoxib. Other NRTIs had no thrombosis-related effects.
Conclusion: Abacavir promotes arterial thrombosis through interference with
purinergic signaling, suggesting a possible biological mechanism for the clinical
association of abacavir with cardiovascular diseases.
PMID- 29346576
TI - Commentary on 'Communicating Messages About Drinking': Using the 'Big Legal Guns'
to Block Alcohol Health Warning Labels.
AB - Like the tobacco industry, the alcohol industry, with the support of governments
in alcohol exporting nations, is looking to international trade and investment
law as a means to oppose health warning labels on alcohol. The threat of such
litigation, let alone its commencement, has the potential to deter all but the
most resolute governments from implementing health warning labeling.
PMID- 29346577
TI - Improved Success Rate of Arterial Puncture for Blood Gas Analysis Through
Standardization.
AB - Background: Arterial puncture for blood gas analysis is a common procedure in
hospitals. The aim of the study is to determine if standardizing technique
elements of the arterial puncture process could improve the success rate of
technicians through the full scope of an academic medical center. Methods: The
study is conducted by the Blood Gas Laboratory at University of Utah Health's
main campus. During the baseline period, technicians tallied whether arterial
puncture attempts were successful or unsuccessful from December 2014 through
February 2015. A small team reviewed the steps of performing arterial puncture
and selected segments of the process for standardization. Starting in March 2015,
staff were trained individually in the standard processes. All staff continued to
tally outcomes of puncture attempts through March 2017. Results: During the
baseline period, the puncture success rate was 83.6%. From April 2015 through
March 2017 the success rate was 89.2%. Conclusion: Standardizing arterial
puncture technique for blood gas analysis leads to fewer punctures.
PMID- 29346578
TI - Effect of daidzein and equol on DNA replication in MCF-7 cells.
AB - It has been reported that daidzein and equol stimulate DNA replication and
proliferation of MCF-7 cells. However, their molecular mechanisms of action are
still unclear. We examined the effects of daidzein and equol on DNA replication
of MCF-7 cells, focusing on MCM2-7 proteins, which function as the replicative
helicase. In the presence of either 1 MUM of daidzein or equol, the number of
cells in S-phase, which was determined by detecting bromodeoxyuridine
incorporated into replicated DNA, almost doubled. The total amounts of MCM7
protein and chromatin-bound MCM7 protein increased in the presence of daidzein.
The data suggest that phytoestrogens facilitate cell cycle progression in G1
phase by increasing the level of MCM proteins. In the presence of phytoestrogens,
phosphorylation of Rb and levels of MCM2, 3 and 7 mRNA increased, suggesting that
stimulation of MCM2-7 transcription is involved in the cell cycle progression.
Under the same conditions, double-stranded DNA breakage in logarithmically
growing MCF-7 cells, which was detected using anti-gamma-H2AX antibodies, did not
increase in the presence of equol.
PMID- 29346579
TI - Web-Based Cognitive Behavior Therapy for Chronic Pain Patients with Aberrant Drug
Related Behavior: Outcomes from a Randomized Controlled Trial.
AB - Objective: There is high unmet need for effective behavioral treatments for
chronic pain patients at risk for or with demonstrated histories of opioid
misuse. Despite growing evidence supporting technology-based delivery of self
management interventions for chronic pain, very few such programs target co
occurring chronic pain and aberrant drug-related behavior. This randomized
controlled trial evaluated the effectiveness of a novel, web-based self
management intervention, grounded in cognitive behavior therapy, for chronic pain
patients with aberrant drug-related behavior. Methods: Opioid-treated chronic
pain patients at a specialty pain practice who screened positive for aberrant
drug-related behavior (N = 110) were randomized to receive treatment as usual
plus the web-based program or treatment as usual alone. The primary outcomes of
pain severity, pain interference, and aberrant drug-related behavior, and the
secondary outcomes of pain catastrophizing and pain-related emergency department
visits, were assessed during the 12-week intervention and at one and three months
postintervention. Results: Patients assigned to use the web-based program
reported significantly greater reductions in aberrant drug-related behavior, pain
catastrophizing, and pain-related emergency department visits-but not pain
severity or pain interference-relative to those assigned to treatment as usual.
The positive outcomes were observed during the 12-week intervention and for three
months postintervention. Conclusions: A web-based self-management program, when
delivered in conjunction with standard specialty pain treatment, was effective in
reducing chronic pain patients' aberrant drug-related behavior, pain
catastrophizing, and emergency department visits for pain. Technology-based self
management tools may be a promising therapeutic approach for the vulnerable group
of chronic pain patients who have problems managing their opioid medication.
PMID- 29346581
TI - Melatonin attenuates lung ischaemia-reperfusion injury via inhibition of
oxidative stress and inflammation.
AB - OBJECTIVES: Lung ischaemia-reperfusion injury is a complex pathophysiological
process due to the production of reactive oxygen species and the generation of
inflammatory reaction. We investigated the protective effects and the
corresponding mechanism of melatonin (MT), a potent free-radical scavenger, on
lung injury induced by ischaemia-reperfusion in a mouse model. METHODS: Adult
male C57BL/6J mice (n = 30) were randomly and equally allocated into 5 groups:
sham controls, IR, IR + 10 mg/kg MT, IR + 20 mg/kg MT and IR + 30 mg/kg MT. Lung
ischaemia-reperfusion injury was induced by thoracotomy followed by clamping of
the left hilum for 1 h and subsequent reperfusion for 2 h. RESULTS: Histological
scoring analysis showed that lung parenchymal damage was ameliorated in the
melatonin pretreatment groups when compared with the IR group, with the IR + 20
mg/kg MT group showing the strongest effect among the melatonin pretreatment
groups. Wet-to-dry weight ratio, detection of malondialdehyde, protein
expressions of inflammatory factors (tumour necrosis factor-alpha, interleukin
1beta, NF-kappaB and IKK-gamma) and apoptotic factors (cleaved caspase-3 and
Bax/Bcl-2), as well as TUNEL assay showed changes similar to those of the lung
injury scores in all groups. In contrast, the examination of superoxide dismutase
showed a pattern contrary to that of the lung injury score in all groups. In
addition, immunohistochemistry staining showed that the expressions of the
antioxidants glutathione peroxidase and glutathione reductase were increased in
the melatonin pretreatment groups. CONCLUSIONS: This study demonstrated that
melatonin pretreatment attenuated lung ischaemia-reperfusion injury via
inhibition of oxidative stress, inflammation and apoptosis.
PMID- 29346582
TI - It's not just 'What' you do, it's also the 'Way' that you do it: Patient and
Public Involvement in the Development of Health Research.
AB - Purpose: This article presents a reflective account of Patient and Public
Involvement (PPI) in the development of obesity and binge eating research.
Method: We established Patient Advisory Groups (PAGs) at two English regional
National Health Service (NHS) weight management services. PPI was evaluated as
follows: (i) PAG members completed a Post Participation Evaluation Questionnaire,
(ii) PAG meetings captured group discussion on PPI involvement, (iii)
practitioner and researchers produced written reflections on PPI and (iv) sources
one to three were consolidated during reflections that took place via e-mail and
telephone correspondence between researchers and practitioners, culminating in a
summary SKYPE meeting between one practitioner and one researcher involved in the
PAGs. Results: Results in the form of reflections suggest guidelines on
undertaking PPI were helpful with regard 'what to do', but less helpful on 'how'.
For example, suggestions for the management of interpersonal factors such as
eliciting self-disclosure and managing power differentials are insufficiently
addressed in existing guidelines. Conclusions: The present case study illustrated
how interpersonal considerations can help or hinder the optimal use of PPI.
Recommendations for practitioners and researchers planning PPI are offered.
PMID- 29346580
TI - Smoking, Sex, and Non-Small Cell Lung Cancer: Steroid Hormone Receptors in Tumor
Tissue (S0424).
AB - Background: To what extent steroid hormones contribute to lung cancer in male and
female never smokers and smokers is unclear. We examined expression of hormone
receptors in lung tumors by sex and smoking. Methods: Patients with primary non
small cell lung cancer were recruited into an Intergroup study in the United
States and Canada, led by SWOG (S0424). Tumors from 813 cases (450 women and 363
men) were assayed using immunohistochemistry for estrogen receptor (ER)-alpha, ER
beta, progesterone receptor (PR), and human epidermal growth factor receptor 2
(HER2). Linear regression was used to examine differences in expression by sex
and smoking status. Cox proportional hazard models were used to estimate survival
associated with the receptors. All statistical tests were two-sided. Results: In
ever smokers, postmenopause and oral contraceptive use were associated with lower
nuclear ER-beta (P = .02) and total (nuclear + cytoplasmic) PR expression (P =
.02), respectively. Women had lower cytoplasmic ER-alpha (regression coefficient
[beta], or differences in H-scores = -15.8, P = .003) and nuclear ER-beta (beta =
-12.8, P = .04) expression than men, adjusting for age, race, and smoking. Ever
smokers had both higher cytoplasmic ER-alpha (beta = 45.0, P < .001) and ER-beta
(beta = 25.9, P < .001) but lower total PR (beta = -42.1, P < .001) than never
smokers. Higher cytoplasmic ER-alpha and ER-beta were associated with worse
survival (hazard ratio = 1.73, 95% confidence interval [CI] = 1.15 to 2.58, and
HR = 1.59, 95% CI = 1.08 to 2.33, respectively; quartiles 4 vs 1). Conclusions:
Lower expression of nuclear ER-beta in women supports the estrogen hypothesis in
lung cancer etiology. Increasing cytoplasmic ER-alpha and ER-beta and decreasing
PR protein expression may be mechanisms whereby smoking disrupts hormone
pathways.
PMID- 29346583
TI - DataMed - an open source discovery index for finding biomedical datasets.
AB - Objective: Finding relevant datasets is important for promoting data reuse in the
biomedical domain, but it is challenging given the volume and complexity of
biomedical data. Here we describe the development of an open source biomedical
data discovery system called DataMed, with the goal of promoting the building of
additional data indexes in the biomedical domain. Materials and Methods: DataMed,
which can efficiently index and search diverse types of biomedical datasets
across repositories, is developed through the National Institutes of Health
funded biomedical and healthCAre Data Discovery Index Ecosystem (bioCADDIE)
consortium. It consists of 2 main components: (1) a data ingestion pipeline that
collects and transforms original metadata information to a unified metadata
model, called DatA Tag Suite (DATS), and (2) a search engine that finds relevant
datasets based on user-entered queries. In addition to describing its
architecture and techniques, we evaluated individual components within DataMed,
including the accuracy of the ingestion pipeline, the prevalence of the DATS
model across repositories, and the overall performance of the dataset retrieval
engine. Results and Conclusion: Our manual review shows that the ingestion
pipeline could achieve an accuracy of 90% and core elements of DATS had varied
frequency across repositories. On a manually curated benchmark dataset, the
DataMed search engine achieved an inferred average precision of 0.2033 and a
precision at 10 (P@10, the number of relevant results in the top 10 search
results) of 0.6022, by implementing advanced natural language processing and
terminology services. Currently, we have made the DataMed system publically
available as an open source package for the biomedical community.
PMID- 29346584
TI - In vitro interactions between IAP antagonist AT406 and azoles against planktonic
cells and biofilms of pathogenic fungi Candida albicans and Exophiala
dermatitidis.
AB - In vitro interactions of AT406, a novel IAP antagonist, and azoles including
itraconazole, voriconazole, and fluconazole against planktonic cells and biofilms
of Candida albicans and Exophiala dermatitidis were assessed via broth
microdilution checkerboard technique. AT406 alone exhibited limited antifungal
activity. However, synergistic effect between AT406 and fluconazole was observed
against both planktonic cells and biofilms of C. albicans, including one
fluconazole-resistant strain. Moreover, synergism was also demonstrated between
AT406 and itraconazole against both planktonic cells and biofilms of E.
dermatitidis. No interaction was observed between AT406 and voriconazole. No
antagonism was observed in all combinations.
PMID- 29346585
TI - Maternal Vaccination With a Monocomponent Pertussis Toxoid Vaccine Is Sufficient
to Protect Infants in a Baboon Model of Whooping Cough.
AB - Background: Bordetella pertussis is a human pathogen responsible for serious
respiratory illness. The disease is most severe in infants too young to be
vaccinated with most hospitalizations and deaths occurring within this age group.
The Advisory Committee on Immunization Practices recommended immunization of
pregnant women to protect infants from birth until their first vaccination at 6-8
weeks of age. We previously demonstrated that maternal vaccination with licensed
acellular pertussis vaccines protected newborn baboons from disease. We
hypothesized that protection was due to toxin-neutralizing, maternal anti
pertussis toxin antibodies and predicted that maternal vaccination with a
pertussis toxoid (PTx)-only vaccine would protect newborns from disease. Methods:
Infant baboons born to unvaccinated mothers or mothers vaccinated with a PTx-only
vaccine were challenged with B. pertussis at 5 weeks of age and followed for
infection and signs of disease. Results: Although all challenged infants were
heavily colonized, the infant baboons born to mothers vaccinated with PTx-only
vaccine were free from clinical disease following exposure to B. pertussis. In
contrast, disease was observed in infants born to unvaccinated mothers.
Conclusions: Our results demonstrated that maternal vaccination with a PTx-only
vaccine is sufficient to protect newborn baboons from disease following exposure
to pertussis.
PMID- 29346586
TI - PlasFlow: predicting plasmid sequences in metagenomic data using genome
signatures.
AB - Plasmids are mobile genetics elements that play an important role in the
environmental adaptation of microorganisms. Although plasmids are usually
analyzed in cultured microorganisms, there is a need for methods that allow for
the analysis of pools of plasmids (plasmidomes) in environmental samples. To that
end, several molecular biology and bioinformatics methods have been developed;
however, they are limited to environments with low diversity and cannot recover
large plasmids. Here, we present PlasFlow, a novel tool based on genomic
signatures that employs a neural network approach for identification of bacterial
plasmid sequences in environmental samples. PlasFlow can recover plasmid
sequences from assembled metagenomes without any prior knowledge of the
taxonomical or functional composition of samples with an accuracy up to 96%. It
can also recover sequences of both circular and linear plasmids and can perform
initial taxonomical classification of sequences. Compared to other currently
available tools, PlasFlow demonstrated significantly better performance on test
datasets. Analysis of two samples from heavy metal-contaminated microbial mats
revealed that plasmids may constitute an important fraction of their metagenomes
and carry genes involved in heavy-metal homeostasis, proving the pivotal role of
plasmids in microorganism adaptation to environmental conditions.
PMID- 29346587
TI - Are root cause analyses recommendations effective and sustainable? An
observational study.
AB - Objective: To assess the strength of root cause analysis (RCA) recommendations
and their perceived levels of effectiveness and sustainability. Design: All RCAs
related to sentinel events (SEs) undertaken between the years 2010 and 2015 in
the public health system in Victoria, Australia were analysed. The type and
strength of each recommendation in the RCA reports were coded by an expert
patient safety classifier using the US Department of Veteran Affairs type and
strength criteria. Participants and setting: Thirty-six public health services.
Main outcome measure(s): The proportion of RCA recommendations which were
classified as 'strong' (more likely to be effective and sustainable), 'medium'
(possibly effective and sustainable) or 'weak' (less likely to be effective and
sustainable). Results: There were 227 RCAs in the period of study. In these RCAs,
1137 recommendations were made. Of these 8% were 'strong', 44% 'medium' and 48%
were 'weak'. In 31 RCAs, or nearly 15%, only weak recommendations were made. In
24 (11%) RCAs five or more weak recommendations were made. In 165 (72%) RCAs no
strong recommendations were made. The most frequent recommendation types were
reviewing or enhancing a policy/guideline/documentation, and training and
education. Conclusions: Only a small proportion of recommendations arising from
RCAs in Victoria are 'strong'. This suggests that insights from the majority of
RCAs are not likely to inform practice or process improvements. Suggested
improvements include more human factors expertise and independence in
investigations, more extensive application of existing tools that assist teams to
prioritize recommendations that are likely to be effective, and greater use of
observational and simulation techniques to understand the underlying systems
factors. Time spent in repeatedly investigating similar incidents may be better
spent aggregating and thematically analysing existing sources of information
about patient safety.
PMID- 29346589
TI - Urban Evolutionary Ecology and the Potential Benefits of Implementing Genomics.
AB - Urban habitats are quickly becoming exceptional models to address adaptation
under rapid environmental change, given the expansive temporal and spatial scales
with which anthropogenic landscape conversion occurs. Urban ecologists in the
last 10-15 years have done an extraordinary job of highlighting phenotypic
patterns that correspond with urban living, as well as delineating urban
population structure using traditional genetic markers. The underpinning genetic
mechanisms that govern those phenotypic patterns, however, are less well
established. Moreover, the power of traditional molecular studies is constrained
by the number of markers being evaluated, which limits the potential to assess
fine-scale population structure potentially common in urban areas. With the
recent proliferation of low-cost, high-throughput sequencing methods, we can
begin to address an emerging question in urban ecology: are species adapted to
local optima within cities or are they expressing latent phenotypic plasticity?
Here, I provide a comprehensive review of previous urban ecological studies, with
special focus on the molecular ecology and phenotypic adjustments documented in
urban terrestrial and amphibious fauna. I subsequently pinpoint areas in the
literature that could benefit from a genomic investigation and briefly discuss
the suitability of specific techniques in addressing eco-evolutionary questions
within urban ecology. Though many challenges exist with implementing genomics
into urban ecology, such studies provide an exceptional opportunity to advance
our understanding of eco-evolutionary processes in metropolitan areas.
PMID- 29346590
TI - Hellenic Society of Cardiology International Congress 2017.
PMID- 29346588
TI - Genome Sequencing of Museum Specimens Reveals Rapid Changes in the Genetic
Composition of Honey Bees in California.
AB - The western honey bee, Apis mellifera, is an enormously influential pollinator in
both natural and managed ecosystems. In North America, this species has been
introduced numerous times from a variety of different source populations in
Europe and Africa. Since then, feral populations have expanded into many
different environments across their broad introduced range. Here, we used whole
genome sequencing of historical museum specimens and newly collected modern
populations from California (USA) to analyze the impact of demography and
selection on introduced populations during the past 105 years. We find that
populations from both northern and southern California exhibit pronounced genetic
changes, but have changed in different ways. In northern populations, honey bees
underwent a substantial shift from western European to eastern European ancestry
since the 1960s, whereas southern populations are dominated by the introgression
of Africanized genomes during the past two decades. Additionally, we identify an
isolated island population that has experienced comparatively little change over
a large time span. Fine-scale comparison of different populations and time points
also revealed SNPs that differ in frequency, highlighting a number of genes that
may be important for recent adaptations in these introduced populations.
PMID- 29346591
TI - Eduardo Marban MD PhD.
PMID- 29346593
TI - HEART Group meeting.
PMID- 29346592
TI - The ESC DAPT Guidelines 2017.
PMID- 29346594
TI - The heart in embryology.
PMID- 29346595
TI - 'Ten Commandments' of the 2017 ESC DAPT focused update Guidelines.
PMID- 29346596
TI - Dual antiplatelet therapy: how, how long, and in which patients?
PMID- 29346597
TI - Exenatide Increases IL-1RA Concentration and Induces Nrf-2-Keap-1-Regulated
Antioxidant Enzymes: Relevance to beta-Cell Function.
AB - Purpose: We previously demonstrated the anti-inflammatory and antioxidant effects
of exenatide. We now hypothesized that exenatide also increases the plasma
concentration of interleukin-1 receptor antagonist (IL-1RA), an endogenous anti
inflammatory protein, and modulates the nuclear factor erythroid 2-related factor
Kelchlike ECH-associated protein 1-antioxidant response element (Nrf-2-Keap-1
ARE) system to induce key antioxidant enzymes to suppress inflammatory and
oxidative stress. Methods: Twenty-four patients with obesity and type 2 diabetes
receiving combined oral and insulin therapy were randomly assigned to receive
either exenatide 10 MUg or placebo twice a day for 12 weeks. Results: Exenatide
increased IL-1RA concentration by 61% (from 318 +/- 53 to 456 +/- 88 pg/mL; P <
0.05). Exenatide treatment also suppressed Keap-1 protein (P < 0.05) and
increased messenger RNA expression of NQO-1, glutathione S-transferase PI, heme
oxygenase-1, and p21 and increased NAD(P)H dehydrogenase [quinone] 1 protein (P <
0.05) in mononuclear cells. Conclusions: Because IL-1RA protects, maintains, and
stimulates beta-cell function in humans and Nrf-2-Keap-1-ARE protects beta cells
in animals with experimental diabetes, these actions of exenatide may contribute
to a potential protective effect on beta cells in diabetes.
PMID- 29346598
TI - Accuracy of preoperative staging for a priori resectable esophageal cancer.
AB - This study assessed the accuracy of preoperative staging in patients undergoing
oncological esophagectomy for adenocarcinoma and squamous cell carcinoma. All
patients undergoing surgery for resectable esophageal cancer in a university
hospital from 2005 to 2016 were identified from our institutional database.
Patients with neoadjuvant treatment were excluded to avoid bias from down-staging
effects. Routinely, all patients had an upper endoscopy with biopsy, a
thoracoabdominal CT scan, an 18-FEG PET-CT, and endoscopic ultrasound.
Preoperative staging was compared to histopathological staging of surgical
specimen that was considered as gold standard. There were 51 patients with a
median age of 65 years (IQR: 59.3-73 years) having 21 squamous cell carcinoma and
30 adenocarcinoma, respectively. T- and N-stages were correctly predicted in 26
(51%) and 37 patients (72%), respectively. Overall, 18 patients (35%) were
preoperatively diagnosed with a correct T- and N-stage. There was no difference
between adenocarcinoma and squamous cell carcinoma. Accuracy of the T-stage was
not influenced by the smoking status. The N-stage was not correct in 7/22 smoking
patients (32%) and 6/29 nonsmoking patients (21%).The N-stage was underestimated
in smoking patients as 6/22 patients (27%) had a histologically confirmed N+ who
were preoperatively classified as N0. In conclusion, only 35% of patients had a
correct assessment. Separate T- and N-stage prediction was improved with 51% and
72%, respectively. Major efforts are needed for improvement.
PMID- 29346599
TI - Magnetic Resonance Imaging-Guided Laser Interstitial Thermal Therapy for the
Treatment of Hypothalamic Hamartomas: A Retrospective Review.
AB - BACKGROUND: Hypothalamic hamartomas (HH) are rare lesions associated with
treatment-resistant epilepsy. Open surgery results in modest seizure control
(about 50%) but has a significant associated morbidity. Radiosurgery is limited
to a subset of patients due to latent therapeutic effects. Magnetic resonance
imaging-guided laser interstitial thermal therapy (LITT) offers a novel minimally
invasive option. OBJECTIVE: To evaluate a single center's outcomes for the LITT
treatment of HH. METHODS: We retrospectively reviewed our experience with LITT
for the treatment of HH using our institution's prospectively maintained patient
database. RESULTS: Eighteen patients (mean age, 21.1 yr; median age, 11 yr)
underwent 21 total LITT treatments for HH. Mean follow-up was 17.4 mo. The length
of stay was 1 night for 16 (89%) patients. At the end of follow-up, 11 of 18
patients (61%) had full disconnection of the HH, and 12 of 15 (80%) patients with
gelastic seizures and 5 (56%) of 9 patients with nongelastic seizures were
seizure free (International League Against Epilepsy Class 1). Immediate
complications included a 39% (7/18) incidence of neurological deficits, including
1 case of hemiparesis. At the end of follow-up, 22% of patients (4/18) had
persistent deficits. The hypothyroidism that occurred was delayed in 11% of
patients (2/18), as was short-term memory loss (22%, 4/18) and weight gain (22%,
4/18). CONCLUSION: LITT therapy for HH can achieve excellent rates of seizure
control with low morbidity and a short postoperative stay in a majority of
patients. Additional research is needed to assess the durability of results and
the full spectrum of cognitive outcomes.
PMID- 29346600
TI - PD-1 blockade in HIV-infected patients with lung cancer: a new challenge or
already a strategy?
PMID- 29346601
TI - Accumulation of Mutational Load at the Edges of a Species Range.
AB - Why species have geographically restricted distributions is an unresolved
question in ecology and evolutionary biology. Here, we test a new explanation
that mutation accumulation due to small population size or a history of range
expansion can contribute to restricting distributions by reducing population
growth rate at the edge. We examined genomic diversity and mutational load across
the entire geographic range of the North American plant Arabidopsis lyrata,
including old, isolated populations predominantly at the southern edge and
regions of postglacial range expansion at the northern and southern edges.
Genomic diversity in intergenic regions declined toward distribution edges and
signatures of mutational load in exon regions increased. Genomic signatures of
mutational load were highly linked to phenotypically expressed load, measured as
reduced performance of individual plants and lower estimated rate of population
growth. The geographic pattern of load and the connection between load and
population growth demonstrate that mutation accumulation reduces fitness at the
edge and helps restrict species' distributions.
PMID- 29346602
TI - How Can We Best Protect Infants from Pertussis?
PMID- 29346603
TI - Homologous stress adaptation, antibiotic resistance, and biofilm forming ability
of Salmonella enterica serovar Heidelberg ATCC8326 on different food-contact
surfaces following exposure to sublethal chlorine concentrations1.
AB - Salmonella enterica serovar Heidelberg (American Type Culture Collection; ATCC
8326) was examined for the ability to adapt to the homologous stress of chlorine
through exposure to increasing chlorine concentrations (25 ppm daily increments)
in tryptic soy broth (TSB). The tested strain exhibited an acquired tolerance to
chlorine in TSB with the tolerant cells growing in concentrations up to 400 ppm.
In addition, the chlorine stressed cells displayed rugose morphology on tryptic
soy agar (TSA) plates at 37 degrees C. The minimum inhibitory concentration (MIC)
of chlorine for adapted (rugose and smooth) cells was determined to be 550 ppm
and 500 ppm, respectively whereas the MIC for the control was 450 ppm. The
biofilm forming ability of the adapted and control cells were examined on both
plastic and stainless steel surface at room temperature and 37 degrees C. The
rugose variant, in contrast to the smooth (adapted and control) showed the
ability to form strong biofilms (P <= 0.05) on a plastic surface at room
temperature and 37 degrees C. Rugose cells compared to smooth and control
attached more (P <= 0.05) to steel surfaces as well. The possibility of cross
adaptation was examined by exposing the adapted and control cells to different
antibiotics according to the Clinical & Laboratory Standards Institute
guidelines. Adapted cells exhibited reduced susceptibility to some of the
antibiotics tested as compared to control. The findings of this study suggest
that exposure to sublethal chlorine concentration during the sanitization
procedure can result in tolerant Salmonella cells. Chlorine may confer cross
protection that aids in the survival of the tolerant population to other
environmental stresses.
PMID- 29346604
TI - Unique genetic profiles from cerebrospinal fluid cell-free DNA in leptomeningeal
metastases of EGFR-mutant non-small-cell lung cancer: a new medium of liquid
biopsy.
AB - Background: Leptomeningeal metastases (LM) are more frequent in non-small-cell
lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due
to limited access to leptomeningeal lesions, the purpose of this study was to
explore the potential role of cerebrospinal fluid (CSF) as a source of liquid
biopsy in patients with LM. Patients and methods: Primary tumor, CSF, and plasma
in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients
with suspected LM underwent lumbar puncture, and those with EGFR mutations
diagnosed with LM were enrolled. Results: A total of 28 patients were enrolled in
this cohort; CSF and plasma were available in 26 patients, respectively. Driver
genes were detected in 100% (26/26), 84.6% (22/26), and 73.1% (19/26) of samples
comprising CSF cell-free DNA (cfDNA), CSF precipitates, and plasma, respectively;
92.3% (24/26) of patients had much higher allele fractions in CSF cfDNA than the
other two media. Unique genetic profiles were captured in CSF cfDNA compared with
those in plasma and primary tissue. Multiple copy number variations (CNVs) were
mainly identified in CSF cfDNA, and MET copy number gain identified in 47.8%
(11/23) of patients was the most frequent one, while other CNVs included ERBB2,
KRAS, ALK, and MYC. Moreover, loss of heterozygosity (LOH) of TP53 was identified
in 73.1% (19/26) CSF cfDNA, which was much higher than that in plasma (2/26,
7.7%; P < 0.001). There was a trend towards a higher frequency of concomitant
resistance mutations in patients with TP53 LOH than those without (70.6% versus
33.3%; P = 0.162). EGFR T790M was identified in CSF cfDNA of 30.4% (7/23) of
patients who experienced TKI progression. Conclusion: CSF cfDNA could reveal the
unique genetic profiles of LM and should be considered as the most representative
liquid biopsy medium for LM in EGFR-mutant NSCLC.
PMID- 29346605
TI - The US Food and Drug Administration's use of regular approval for cancer drugs
based on single-arm studies: implications for subsequent evidence generation.
PMID- 29346606
TI - Characteristics of Cases With Repeated Sexually Transmitted Infections,
Massachusetts, 2014-2016.
AB - Background: Persons with prior sexually transmitted infections (STIs) are at high
risk for reinfection. No recent studies have examined frequency with which
persons are diagnosed and reported with multiple bacterial STIs over time.
Methods: We conducted a retrospective, of confirmed syphilis, gonorrhea, and
chlamydial infections reported to Massachusetts state surveillance system within
a 2-year period, 28 July 2014-27 July 2016. Results: Among Massachusetts
population aged 13-65 years (4847510), 49142 (1.0%) were reported with >=1 STIs;
6999 (14.2% of those with >=1 STI) had >=2 STIs, accounting for 27.7% of STIs. Of
cases with >=5 or more STIs (high-volume repeaters), 118 (74%) were men and 42
(26%) were women. Men spanned the age spectrum and were predominantly non
Hispanic white; 87% reported same-sex contacts. Women were younger, predominantly
nonwhite, and without known same-sex contacts. Women were reinfected with
gonorrhea and chlamydia or chlamydia alone; none had syphilis or human
immunodeficiency virus (HIV) infection. All men with syphilis also had gonorrhea
and/or chlamydia; 35% were diagnosed with HIV before, during, or within 10 months
after study period. The majority (56%) of high-volume repeaters were seen at more
than 1 care site/system. Conclusions: In Massachusetts, a large proportion of
bacterial STIs are reported from a small subpopulation, many of whom have
repeated infections and are likely to have higher impact on STI and HIV rates.
Public health can play a crucial role in reaching high-volume repeaters whose STI
histories may be hidden from clinicians due to fragmented care.
PMID- 29346607
TI - Combined Endovascular and Microsurgical Treatment of a Premotor Arteriovenous
Malformation: 2-Dimensional Operative Video.
PMID- 29346608
TI - On-Demand Intraoperative 3-Dimensional Printing of Custom Cranioplastic
Prostheses.
AB - BACKGROUND: Currently, implantation of patient-specific cranial prostheses
requires reoperation after a period for design and formulation by a third-party
manufacturer. Recently, 3-dimensional (3D) printing via fused deposition modeling
has demonstrated increased ease of use, rapid production time, and significantly
reduced costs, enabling expanded potential for surgical application. Three
dimensional printing may allow neurosurgeons to remove bone, perform a rapid
intraoperative scan of the opening, and 3D print custom cranioplastic prostheses
during the remainder of the procedure. OBJECTIVE: To evaluate the feasibility of
using a commercially available 3D printer to develop and produce on-demand
intraoperative patient-specific cranioplastic prostheses in real time and assess
the associated costs, fabrication time, and technical difficulty. METHODS: Five
different craniectomies were each fashioned on 3 cadaveric specimens (6 sides) to
sample regions with varying topography, size, thickness, curvature, and
complexity. Computed tomography-based cranioplastic implants were designed,
formulated, and implanted. Accuracy of development and fabrication, as well as
implantation ability and fit, integration with exiting fixation devices, and
incorporation of integrated seamless fixation plates were qualitatively
evaluated. RESULTS: All cranioprostheses were successfully designed and printed.
Average time for design, from importation of scan data to initiation of printing,
was 14.6 min and average print time for all cranioprostheses was 108.6 min.
CONCLUSION: On-demand 3D printing of cranial prostheses is a simple, feasible,
inexpensive, and rapid solution that may help improve cosmetic outcomes;
significantly reduce production time and cost-expanding availability; eliminate
the need for reoperation in select cases, reducing morbidity; and has the
potential to decrease perioperative complications including infection and
resorption.
PMID- 29346609
TI - Decreased Serum Levels of Ghrelin and Brain-Derived Neurotrophic Factor in
Premenopausal Women With Metabolic Syndrome.
AB - Objective: We aimed to investigate the association between serum levels of
ghrelin and brain-derived neurotrophic factor (BDNF) with MetS and its components
in premenopausal women. Methods: 43 patients with MetS and 43 healthy controls
participated in this study. Participants' body mass index (BMI), waist
circumference (WC), systolic and diastolic blood pressure (SBP and DBP) were
measured. Serum levels of total cholesterol (TC), triglyceride (TG), low and high
density lipoprotein cholesterol (LDL-C and HDL-C), fasting blood sugar (FBS),
insulin, BDNF and ghrelin determined. Homeostasis model assessment insulin
resistance index (HOMA-IR) was also calculated. Results: Participants in MetS
group had higher waist-to-hip ratios, elevated SBP and DBP, and higher serum
levels of TG, FBS and insulin when compared with the control group. Serum ghrelin
and BDNF levels were significantly lower in participants with MetS than in the
healthier control subjects. There was a strong, positive correlation between
serum ghrelin and BDNF levels. Both proteins negatively correlated with TG, FBS,
HOMA-IR and positively with HDL-C. Furthermore, serum BDNF levels negatively
associated with insulin levels. Conclusions: The findings indicate that
variations occur in the circulating level of ghrelin and BDNF proteins in MetS
patients. A strong correlation between serum ghrelin and BDNF suggests that
production, release or practice of these 2 proteins might be related
mechanically.
PMID- 29346610
TI - Novel mutations in the lipase H gene lead to secretion defects of LIPH in Chinese
patients with autosomal recessive woolly hair/hypotrichosis (ARWH/HT).
AB - Autosomal recessive woolly hair/hypotrichosis (ARWH/HT: OMIM #278150/604379) is a
rare hereditary hair disease characterized by tightly curled hair at birth which
can lead to sparse hair later in life. The mutations in both LIPH and LPAR6/P2RY5
are responsible for autosomal recessive woolly hair with or without hypotrichosis
(ARWH/HT). To conduct clinical and genetic investigations in four patients from
three unrelated Chinese Han families with ARWH/HT, we performed mutation
screening of LIPH and LPAR6/P2RY5 gene and identified four mutations in LIPH:
c.454G>A, c.614A>G, c.736T>A, c.742C>A. c.736T>A and c.742C>A mutations were
reported in previous studies, and c.454G>A, c.614A>G were identified for the
first time. We carried out functional studies of the two mutants with c.454G>A
(p.Gly152Arg, G152R) or c.614A>G (p.His205Arg, H205R). Interestingly, both of
them lead to secretion defects of LIPH, which are involved in the pathogenesis of
ARWH/HT.
PMID- 29346612
TI - Hyperpyrexia in a patient with a left ventricular assist device: a diagnosis
beyond the obvious.
AB - As the number of patients receiving a left ventricular assist device increases,
physicians must always keep in mind that several conditions can present with non
specific symptoms, such as fever, tachypnoea and confusion. We herein report the
case of a left ventricular assist device patient who developed a life-threatening
condition with acute hyperthermia, confusion and extremities' clonus and muscle
spasms. The patient was diagnosed with serotonin syndrome, attributed to the
coadministration of 2 commonly prescribed medications (citalopram and
omeprazole). This case highlights that a significant proportion of left
ventricular assist device patients is treated with serotonergic agents that may
predispose them to the appearance of serotonin syndrome, a potentially life
threatening condition.
PMID- 29346611
TI - Combined roles of ATP and small hairpin RNA in the activation of RIG-I revealed
by solution-based analysis.
AB - RIG-I (retinoic acid inducible gene-I) is a cytosolic innate immune protein that
senses viral dsRNA with a 5'-triphosphate overhang. Upon interaction with dsRNA a
de-repression of the RIG-I CARD domains takes place that ultimately leads to the
production of type I interferons and pro-inflammatory cytokines. Here we
investigate the RIG-I conformational rearrangement upon interaction with an
activating 5'-triphosphate-10-base pair dsRNA hairpin loop (10bp) compared with a
less active 5'-triphosphate-8-base pair dsRNA hairpin loop (8bp). We use size
exclusion chromatography-coupled small-angle X-ray scattering (SAXS) and limited
tryptic digest experiments to show that that upon binding to 10 bp, but not 8 bp,
RIG-I becomes extended and shows greater flexibility, reflecting the release of
its CARDs. We also examined the effect of different ATP analogues on the
conformational changes of RIG-I/dsRNA complexes. Of the analogues tested, the
addition of ATP transition state analogue ADP-AlFx further assisted in the
complete activation of RIG-I in complex with 10bp and also to some extent RIG-I
bound to 8bp. Together these data provide solution-based evidence for the
molecular mechanism of innate immune signaling by RIG-I as stimulated by short
hairpin RNA and ATP.
PMID- 29346613
TI - Review of chronic non-cancer pain research among Aboriginal people in Canada.
AB - Purpose: Aboriginal people in Canada are disproportionately affected by chronic
illnesses, compared to non-Aboriginal Canadians. The purpose of this review was
to determine whether differences exist between the two groups with respect to
chronic non-cancer pain (CNCP) in order to better inform clinical practice and to
identify research gaps. Data sources: Four electronic databases were searched for
the period of 1990-2015. Study selection: Only English and French language
original studies that examined CNCP prevalence, assessment tools and beliefs
among Aboriginal people in Canada were considered. Data extraction: Data
extracted included Aboriginal group, geographic location, study setting and pain
definition (for prevalence studies only). Results of data synthesis: A total of
11 studies matched the selection criteria: 10 reported estimates of chronic pain
prevalence among Aboriginal people in Canada, 1 was about a culturally adapted
pain assessment tool, and no study was found about CNCP beliefs within Aboriginal
people. Conclusion: CNCP among Aboriginal people is still a largely unexplored
research field. The limited evidence available so far does not allow us to
conclude that CNCP affects a higher proportion of Aboriginal than non-Aboriginal
people in Canada. However, arthritis, a specific condition associated with
chronic pain, is more prevalent in Aboriginal than non-Aboriginal people.
Additional research is needed on other CNCP types and conditions. Furthermore,
pain assessment tools are not culturally adapted and clinicians should inquire
more about the beliefs of Aboriginal patients to make them feel safer and to
better target interventions.
PMID- 29346614
TI - Influenza Vaccine Effectiveness Against Influenza A(H3N2) Hospitalizations in
Children in Hong Kong in a Prolonged Season, 2016/2017.
AB - Background: Influenza A(H3N2) viruses circulated for 12 consecutive months in
Hong Kong in 2016-2017, peaking in late June and July 2017. The objective of our
study was to estimate the effectiveness of influenza vaccination in preventing
hospitalizations in children in Hong Kong. Methods: We conducted a test-negative
study between 1 September 2016 and 31 August 2017, enrolling children 6 months to
17 years of age hospitalized for an acute respiratory infection. Influenza was
diagnosed by PCR on nasopharyngeal aspirates. Results: We enrolled 5514 children,
including 3608 children 6 months to 2 years, 1600 children 3-5 years, and 1206
children 6-17 years of age. Influenza-associated hospitalizations occurred
throughout the study year but time of vaccination of these children was also wide
spread, from September 2016 to May 2017. Influenza vaccine effectiveness (VE) was
39.7% (95% confidence interval [CI], 14.7%-57.3%) against laboratory-confirmed
influenza A(H3N2). In analyses stratified by time since vaccination, the VE
against influenza A(H3N2) was 52.8% (95% CI, 17.1%-73.2%) within 3 months of
vaccination, and 31.2% (95% CI, -6.6% to 55.6%) 4-6 months after vaccination.
Conclusions: Influenza vaccination was effective in preventing hospitalizations
in children in Hong Kong.
PMID- 29346615
TI - The RNA-splicing endonuclease from the euryarchaeaon Methanopyrus kandleri is a
heterotetramer with constrained substrate specificity.
AB - Four different types (alpha4, alpha'2, (alphabeta)2 and epsilon2) of RNA-splicing
endonucleases (EndAs) for RNA processing are known to exist in the Archaea. Only
the (alphabeta)2 and epsilon2 types can cleave non-canonical introns in precursor
(pre)-tRNA. Both enzyme types possess an insert associated with a specific loop,
allowing broad substrate specificity in the catalytic alpha units. Here, the
hyperthermophilic euryarchaeon Methanopyrus kandleri (MKA) was predicted to
harbor an (alphabeta)2-type EndA lacking the specific loop. To characterize MKA
EndA enzymatic activity, we constructed a fusion protein derived from MKA alpha
and beta subunits (fMKA EndA). In vitro assessment demonstrated complete removal
of the canonical bulge-helix-bulge (BHB) intron structure from MKA pre-tRNAAsn.
However, removal of the relaxed BHB structure in MKA pre-tRNAGlu was inefficient
compared to crenarchaeal (alphabeta)2 EndA, and the ability to process the
relaxed intron within mini-helix RNA was not detected. fMKA EndA X-ray structure
revealed a shape similar to that of other EndA types, with no specific loop.
Mapping of EndA types and their specific loops and the tRNA gene diversity among
various Archaea suggest that MKA EndA is evolutionarily related to other
(alphabeta)2-type EndAs found in the Thaumarchaeota, Crenarchaeota and
Aigarchaeota but uniquely represents constrained substrate specificity.
PMID- 29346616
TI - Racial differences in family health history knowledge of type 2 diabetes:
exploring the role of interpersonal mechanisms.
AB - Collecting complete and accurate family health history is critical to preventing
type 2 diabetes. Whether there are any racial difference in family health history
knowledge of type 2 diabetes and whether such differences are related to
interpersonal mechanisms remain unclear. We seek to identify the interpersonal
mechanisms that give rise to discrepancies in family health history knowledge of
type 2 diabetes in families of different racial backgrounds. We analyze informant
dyad consensus with respect to shared family history of type 2 diabetes in 127
informants of 45 families in the greater Cincinnati area (white: 28 families, 78
informants; black/African-American: 17 families, 49 informants). We first
document a difference in informant-dyad consensus by race and then test whether
this difference can be explained by interpersonal ties, particularly health
communication. Compared with their white counterparts, dyads in families of
black/African-American background are more likely to have an uneven distribution
of knowledge, with one informant knowing and the other not knowing his/her family
health history. The racial difference is explained by dyads in families of
black/African-American background having fewer reciprocal health communication
ties. While associated with informant-dyad consensus, education, kinship ties,
and closeness ties do not account for the observed racial difference. Activating
health communication is a key to improving family health history knowledge,
especially in families of black/African-American background. Researchers and
clinicians should leverage communication ties in the family network for better
collection and utilization of family health history in preventive services.
PMID- 29346617
TI - Riboswitching with ciprofloxacin-development and characterization of a novel RNA
regulator.
AB - RNA molecules play important and diverse regulatory roles in the cell. Inspired
by this natural versatility, RNA devices are increasingly important for many
synthetic biology applications, e.g. optimizing engineered metabolic pathways,
gene therapeutics or building up complex logical units. A major advantage of RNA
is the possibility of de novo design of RNA-based sensing domains via an in vitro
selection process (SELEX). Here, we describe development of a novel ciprofloxacin
responsive riboswitch by in vitro selection and next-generation sequencing-guided
cellular screening. The riboswitch recognizes the small molecule drug
ciprofloxacin with a KD in the low nanomolar range and adopts a pseudoknot fold
stabilized by ligand binding. It efficiently interferes with gene expression both
in lower and higher eukaryotes. By controlling an auxotrophy marker and a
resistance gene, respectively, we demonstrate efficient, scalable and
programmable control of cellular survival in yeast. The applied strategy for the
development of the ciprofloxacin riboswitch is easily transferrable to any small
molecule target of choice and will thus broaden the spectrum of RNA regulators
considerably.
PMID- 29346619
TI - Spurious Thrombocytopenia in Automated Platelet Count.
AB - Spurious thrombocytopenia is a well-known phenomenon observed with the widespread
use of hematology analyzers (HAs). In this study, 355 specimens with pseudo
thrombocytopenia (PTCP) were evaluated via epidemiology, identification,
remedies, and platelet (PLT) count. Data showed that anticoagulants such as
citrate and/or heparin-dependent PTCP (16.0%) became increasingly common, whereas
ethylenediaminetetraacetic acid (EDTA)-induced PTCP (49.1%) remained the most
frequent. We note that that nearly half of the patients with PTCP had veritable
decreased PLT counts, even after PLT levels had been corrected. Our findings
suggest that there were seasonal changes in patients with PTCP: PLT levels were
higher in spring, compared with other seasons, with winter levels being the
lowest. There were higher risks of PTCP for individuals with malignant neoplasms,
liver diseases, infection, and hematologic disease, compared with other
conditions. PTCP is related to diseases, rather than being a simple phenomenon,
and thus demands careful attention.
PMID- 29346618
TI - Evidence of Adaptive Evolution and Relaxed Constraints in Sex-Biased Genes of
South American and West Indies Fruit Flies (Diptera: Tephritidae).
AB - Several studies have demonstrated that genes differentially expressed between
sexes (sex-biased genes) tend to evolve faster than unbiased genes, particularly
in males. The reason for this accelerated evolution is not clear, but several
explanations have involved adaptive and nonadaptive mechanisms. Furthermore, the
differences of sex-biased expression patterns of closely related species are also
little explored out of Drosophila. To address the evolutionary processes involved
with sex-biased expression in species with incipient differentiation, we analyzed
male and female transcriptomes of Anastrepha fraterculus and Anastrepha obliqua,
a pair of species that have diverged recently, likely in the presence of gene
flow. Using these data, we inferred differentiation indexes and evolutionary
rates and tested for signals of selection in thousands of genes expressed in head
and reproductive transcriptomes from both species. Our results indicate that sex
biased and reproductive-biased genes evolve faster than unbiased genes in both
species, which is due to both adaptive pressure and relaxed constraints.
Furthermore, among male-biased genes evolving under positive selection, we
identified some related to sexual functions such as courtship behavior and
fertility. These findings suggest that sex-biased genes may have played important
roles in the establishment of reproductive isolation between these species, due
to a combination of selection and drift, and unveil a plethora of genetic markers
useful for more studies in these species and their differentiation.
PMID- 29346620
TI - Combating Global Antibiotic Resistance: Emerging One Health Concerns in Lower-
and Middle-Income Countries.
AB - Antibiotic misuse in lower- and middle-income countries (LMICs) contributes to
the development of antibiotic resistance that can disseminate globally.
Strategies specific to LMICs that seek to reduce antibiotic misuse by humans, but
simultaneously improve antibiotic access, have been proposed. However, most
approaches to date have not considered the growing impact of animal and
environmental reservoirs of antibiotic resistance, which threaten to exacerbate
the antibiotic resistance crisis in LMICs. In particular, current strategies do
not prioritize the impacts of increased antibiotic use for terrestrial food
animal and aquaculture production, inadequate food safety, and widespread
environmental pollution. Here, we propose new approaches that address emerging,
One Health challenges.
PMID- 29346621
TI - Assessing polymyalgia rheumatica activity when C-reactive protein is unavailable
or uninterpretable.
AB - Objective: The PMR activity score (PMR-AS) includes the CRP value, which may be
lacking or invalid owing to anti-IL-6 therapy. Our objective was to develop
alternatives to PMR-AS that do not require CRP. Methods: We used the Club
Rhumatisme et Inflammation (CRI; 89 patients with PMR) and the Tolerance and
Efficacy of tocilizumab iN pOlymyalgia Rheumatica (TENOR; 20 patients with recent
onset PMR naive to glucocorticoid who received three tocilizumab infusions, at
weeks 0, 4 and 8, followed by prednisone from weeks 12 to 24) cohorts. In the CRI
cohort, we evaluated correlations between PMR-AS items to select the best item
for imputing CRP. Then we calculated the PMR-AS with (PMR-AS) and without (clin
PMR-AS) CRP and we used the linear regression between PMR-AS and clin-PMR-AS to
obtain CRP-imputed (CRP-imp) PMR-AS. Finally, we evaluated agreement between clin
PMR-AS, CRP-imp PMR-AS, PMR-AS and ESR-PMR-AS in the TENOR cohort during
tocilizumab therapy. Results: In the CRI cohort, agreement between PMR-AS and
clin-PMR-AS was excellent (kappa = 0.90). Linear regression between PMR-AS and
clin-PMR-AS [CRP-imp PMR-AS = 1.12(clin-PMR-AS)+0.26] allowed us to build the CRP
imp PMR-AS. Mean (s.d.) values were as follows: 8.40 (9.76) for PMR-AS, 7.24
(8.58) for clin-PMR-AS and 7.84 (9.61) for CRP-imp PMR-AS. CRP-imp PMR-AS agreed
more closely with PMR-AS than did clin-PMR-AS. The results in the TENOR cohort
confirmed that CRP-imp PMR-AS or ESR-PMR-AS could be used. Conclusion:
Alternatives to the PMR-AS obtained without CRP can be used to monitor PMR
activity in everyday practice in patients without available CRP values and in
those receiving IL-6 antagonist therapy.
PMID- 29346622
TI - A Nosocomial Foodborne Outbreak of a VIM Carbapenemase-Expressing Citrobacter
freundii.
AB - Background: A foodborne outbreak of VIM carbapenemase-expressing Citrobacter
freundii (CPC) occurred between February 2016 and June 2016 at a major university
hospital in Germany. Methods: An explosive increase in CPC isolated from rectal
swabs of patients during weekly routine screening led to the declaration of an
outbreak. A hospital-wide prevalence screening was initiated as well as screening
of all patients on admission and before transfer to another ward, canteen staff,
patient rooms, medical and kitchen inventory, and food. Swabs were streaked out
on selective plates. All CPC isolates were analyzed using mass spectrometry, and
selected isolates were analyzed using whole-genome sequencing. Results: A total
of 76 were identified; most were unrelated cases in different wards. The CPC was
isolated from retained samples of prepared vegetable salads and puddings and from
a mixing machine used to prepare these foods only after an overnight culture. The
immediate ban on serving potential source food resulted in a sharp decline and
finally disappearance of novel cases. Repeated testing of presliced vegetables
showed a high degree of contamination with C. freundii without a carbapenemase,
indicating a possible source. Conclusions: An explosive increase in carbapenemase
expressing Enterobacteriaceae contamination may have been caused by a foodborne
source, and presliced vegetables should be taken into account as a putative
pathogen repository. These findings underline the importance of appropriate
cooling, transport, reheating, and distribution of meals and indicate that
probing of nonorganic surfaces is limited by low sensitivity, which may be
increased by additional overnight cultivation in appropriate media.
PMID- 29346623
TI - A large-scale field study of bacterial communities in cereal aphid populations
across Morocco.
AB - Insects are frequently associated with bacteria that can have significant
ecological and evolutionary impacts on their hosts. To date, few studies have
examined the influence of environmental factors to microbiome composition of
aphids. The current work assessed the diversity of bacterial communities of five
cereal aphid species (Sitobion avenae, Rhopalosiphum padi, R. maidis, Sipha
maydis and Diuraphis noxia) collected across Morocco, covering a wide range of
environmental conditions. We aimed to test whether symbiont combinations are host
or environment specific. Deep 16S rRNA sequencing enabled us to identify 17
bacterial operational taxonomic units (OTUs). The obligate symbiont Buchnera
aphidicola was represented by five OTUs with multiple haplotypes in many single
samples. Facultative endosymbionts were presented by a high prevalence of
Regiella insecticola and Serratia symbiotica in S. avenae and Si. maydis,
respectively. In addition to these symbiotic partners, Pseudomonas,
Acinetobacter, Pantoea, Erwinia and Staphyloccocus were also identified in
aphids, suggesting that the aphid microbiome is not limited to the presence of
endosymbiotic bacteria. Beside a significant association between host species and
bacterial communities, an inverse correlation was also found between altitude and
alpha-diversity. Overall, our results support that symbiont combinations are
mainly host specific.
PMID- 29346624
TI - Data-driven approaches to define the upper limit of the intermovement interval of
periodic leg movements during sleep.
AB - Study Objectives: To define statistically the upper limit of the intermovement
interval (IMI, the time interval between the onset of consecutive movements) of
periodic leg movements during sleep (PLMS). Methods: We computed the IMI
distribution of a large sample (n = 141) of patients with restless legs syndrome
(RLS) and analyzed it with two independent approaches, based on fitting either
empirical functions or normal and exponential functions to the data. Results: The
two fitting approaches consistently pointed to an upper limit of the PLMS IMI in
the range between 50 and 60 s. Decreasing the upper limit of PLMS IMI from 90 to
60 s evidently decreased the PLMS index in patients with RLS and control
participants; nevertheless, the PLMS index remained significantly higher in RLS
vs. control participants. Shifting the upper limit of PLMS IMI to 60 s did not
significantly modify the effectiveness of discrimination of PLMS between controls
and patients with RLS. Conclusion: These results seem to indicate that a
conservative, yet data-driven upper limit for IMI contributing to the PLMS in
patients with RLS might be 60 s instead of 90 s, as recommended by the present
guidelines.
PMID- 29346626
TI - Anti-aminoacyl tRNA synthetase antibody-positive clinically amyopathic
dermatomyositis.
PMID- 29346625
TI - Complete genomic and transcriptional landscape analysis using third-generation
sequencing: a case study of Saccharomyces cerevisiae CEN.PK113-7D.
AB - Completion of eukaryal genomes can be difficult task with the highly repetitive
sequences along the chromosomes and short read lengths of second-generation
sequencing. Saccharomyces cerevisiae strain CEN.PK113-7D, widely used as a model
organism and a cell factory, was selected for this study to demonstrate the
superior capability of very long sequence reads for de novo genome assembly. We
generated long reads using two common third-generation sequencing technologies
(Oxford Nanopore Technology (ONT) and Pacific Biosciences (PacBio)) and used
short reads obtained using Illumina sequencing for error correction. Assembly of
the reads derived from all three technologies resulted in complete sequences for
all 16 yeast chromosomes, as well as the mitochondrial chromosome, in one step.
Further, we identified three types of DNA methylation (5mC, 4mC and 6mA).
Comparison between the reference strain S288C and strain CEN.PK113-7D identified
chromosomal rearrangements against a background of similar gene content between
the two strains. We identified full-length transcripts through ONT direct RNA
sequencing technology. This allows for the identification of transcriptional
landscapes, including untranslated regions (UTRs) (5' UTR and 3' UTR) as well as
differential gene expression quantification. About 91% of the predicted
transcripts could be consistently detected across biological replicates grown
either on glucose or ethanol. Direct RNA sequencing identified many
polyadenylated non-coding RNAs, rRNAs, telomere-RNA, long non-coding RNA and
antisense RNA. This work demonstrates a strategy to obtain complete genome
sequences and transcriptional landscapes that can be applied to other eukaryal
organisms.
PMID- 29346629
TI - HIV-1 Control and Immunoglobulin Genes.
PMID- 29346627
TI - Severe and protracted sleep disruptions in mouse model of post-traumatic stress
disorder.
AB - Increasing evidences suggest that the predator threat model is a valid animal
model of post-traumatic stress disorder (PTSD). However, sleep has never been
examined in this model. Since sleep disturbances, including insomnia and
excessive daytime sleepiness, are severe and protracted symptoms of PTSD, we
hypothesized that mice exposed to predator odor trauma (POT) will display
contextual fear conditioning along with severe and protracted sleep disruptions.
Adult male C57BL/6J mice, instrumented with wire electrodes (to record
hippocampal local field potentials [LFP] and nuchal muscle [electromyogram, EMG]
activity), were exposed to contextual conditioning using soiled cat litter as
unconditional stimulus (US). On day 1, fear memory acquisition (FMA) training was
performed by exposing mice to contextual cage (conditional stimulus; CS) for 30
min followed by exposure to CS + US for 90 min. On day 5, fear memory recall
(FMR) testing was performed by exposing mice to CS (without US) for 120 min. LFP
and EMG were recorded continuously for 5 days. Mice exposed to POT displayed as
follows: (1) hyperarousal coupled with electrophysiological indicators of memory
acquisition and retrieval (increased hippocampal theta and gamma power) during
FMA and FMR; (2) increased nonrapid eye movement (NREM) delta and rapid eye
movement theta power during sleep post FMA, indicating memory consolidation; (3)
protracted sleep disturbances as evident by increased wakefulness, reduced NREM
sleep and NREM delta power, increased NREM beta power during light (sleep)
period, and increased sleep during dark (active) period. Based on these results,
we suggest that mice exposed to POT display severe and protracted sleep
disturbances mimicking sleep disturbance observed in human PTSD.
PMID- 29346630
TI - Vitamin D Toxicity: A 16-Year Retrospective Study at an Academic Medical Center.
AB - Background: Interest in vitamin D has increased during the past 2 decades, with a
corresponding increase in laboratory testing of 25-hydroxyvitamin D [25(OH)D].
The vast majority of specimens tested display normal or deficient levels of
25(OH)D; concentrations rarely fall in the potentially toxic range. Methods: We
performed a retrospective investigation of elevated 25(OH)D levels during a 16
year period at the University of Iowa Hospitals and Clinics (UIHC), a 734-bed
tertiary-/quaternary-care academic medical center in the midwestern United
States. Detailed medical-record review was performed for patients with
serum/plasma 25(OH)D concentrations higher than 120 ng per mL. Results: A total
of 127,932 serum/plasma 25(OH)D measurements were performed on 73,779 unique
patients. Of these patients, 780 (1.05%) had results that exceeded 80 ng per mL
and 89 patients (0.12%) had results that exceeded 120 ng per mL. Only 4 patients
showed symptoms of vitamin D toxicity. Three of these cases involved inadvertent
misdosing of liquid formulations. Conclusions: Symptomatic vitamin D toxicity is
uncommon, and elevated levels of 25(OH)D do not strongly correlate with clinical
symptoms or total serum/plasma calcium levels. Our study highlights the potential
risks of the liquid formulation of vitamin D.
PMID- 29346631
TI - Anticardiolipin antibodies and 12-month graft function in kidney transplant
recipients: a prognosis cohort survey.
AB - Background: In kidney transplant recipients, anticardiolipin (ACL) antibodies
without antiphospholipid syndrome (APS) are found in up to 38% of patients and
could be associated with thrombotic events (TEs). However, the prognostic role of
ACL regarding kidney transplant and patients outcomes have still not been well
defined. Methods: We conducted an observational, monocentric, retrospective
cohort study including 446 kidney transplant recipients and standardized follow
up: 36-month allograft and patient survival, 12-month estimated glomerular
filtration rate (eGFR) and 3- and 12-month screening biopsies. Results: ACL tests
were run on 247 patients, 101 were positive (ACL+ group, 41%) and 146 were
negative (ACL- group, 59%). Allografts and patient survival within 36 months as
TE were similar between both groups [hazard ratio (HR) = 1.18 and HR = 0.98,
respectively]. The 12-month eGFR was significantly lower in the ACL+ group
[median (95% confidence interval) 48.5 (35.1-60.3) versus 51.9 (39.1-65.0)
mL/min/1.73 m2, P= 0.042]. ACL+ was independently associated with eGFR decrease
(P = 0.04). In 12-month screening biopsies, tubular atrophy was significantly
more severe in the ACL+ group compared with the ACL- group (P = 0.02).
Conclusions: ACL without APS before kidney transplantation is an independent risk
factor of eGFR decline within the first year post-transplant without over
incidence of TEs. Specific immunosuppressive therapy including mammalian target
of rapamycin inhibitors should be discussed in the future.
PMID- 29346632
TI - Diagnostic and Prognostic Value of JC Virus DNA in Plasma in Progressive
Multifocal Leukoencephalopathy.
AB - Background: Progressive multifocal leukoencephalopathy (PML) is a severe
demyelinating disease caused by the polyomavirus JC (John Cunningham; JCV) that
affects patients with impaired immune systems. While JCV-DNA detection in
cerebrospinal fluid (CSF) is diagnostic of PML, the clinical significance of
plasma JCV-DNA is uncertain. Methods: We retrospectively analyzed plasma samples
from PML patients that were drawn close to disease onset and from controls
without PML. In PML patients, we compared plasma JCV-DNA detection and levels to
clinical and laboratory parameters, and patient survival. Results: JCV-DNA was
detected in plasma of 49/103 (48%) patients with PML (20/24, 83%, human
immunodeficiency virus [HIV] negative; 29/79, 37%, HIV-positive) and of 4/144
(3%) controls without PML (0/95 HIV-negative; 4/49, 8%, HIV-positive), yielding a
diagnostic sensitivity and specificity of 48% and 97% (83% and 100% in HIV
negative; 37% and 92% in HIV-positive), respectively. Among 16 PML patients with
undetectable CSF JCV-DNA, 4 (25%) had detectable plasma JCV-DNA. Plasma JCV-DNA
levels were independently associated with CSF levels (P < .0001) and previous
corticosteroid treatment (P = .012). Higher plasma JCV-DNA levels were associated
with disease progression in HIV-negative patients (P = .005); in HIV-positive
patients, there was an increased risk of progression only in those treated with
combination antiretroviral therapy (cART; P < .0001). Conclusions: Testing JCV
DNA in plasma might complement PML diagnosis, especially when CSF is unavailable
or JCV-DNA not detectable in CSF. In addition, JCV-DNA plasma levels could be
useful as a marker of disease progression in both HIV-negative and cART-treated,
HIV-positive PML patients.
PMID- 29346633
TI - Intraoperative epicardial focal pulmonary venous electrocardiography in patients
with atrial fibrillation.
AB - OBJECTIVES: In patients referred to off-pump coronary artery bypass grafting,
pulmonary vein isolation (PVI) may be used for those with persistent atrial
fibrillation (AF), an alternative to the Maze procedure. However, the success
rate of PVI in persistent AF is limited. The study assesses the prognostic value
of focal epicardial electrocardiography of the pulmonary veins (PVs) for surgical
ablation results. METHODS: We mapped 140 PV in 35 cases undergoing off-pump
coronary artery bypass grafting. Data obtained using a sensing-pacing probe
before ablation were analysed. The composite study end-point consisted of the
need for electrical cardioversion for in-hospital recurrence of AF and the
presence of AF at hospital discharge and after 6 months follow-up confirmed by 24
h Holter electrocardiographic monitoring. RESULTS: In patients with epicardial
far-field (FF) signals recorded over at least 1 PV, the composite end-point
occurred in 61% (14) vs 25% (3) of patients with no FF signal recorded over any
PV (P = 0.04). The presence of FF signals in at least 1 PV significantly
increased the risk of composite end-point occurrence (odds ratio 3; P = 0.04).
The composite end-point occurred in 86% (6) of patients with FF signals recorded
over all PVs and in 39% (11) in the remainder of the study population (P = 0.03).
CONCLUSIONS: Intraoperative epicardial focal electrocardiography of PVs revealed
more than 40% of PVs had only FF atrial signals. The presence of FF signals in
PVs is related to a lower early effectiveness of PVI on ablating AF. Epicardial
focal electrocardiography of PVs may be a clinically effective intraoperative
tool in the decision-making process between less invasive PVI and the standard
Maze procedure.
PMID- 29346634
TI - Are people getting quality thalassemia care in twin cities of Pakistan? A
comparison with international standards.
AB - Objectives: This study was conducted to determine if thalassemia patients were
getting quality care in Rawalpindi and Islamabad, Pakistan, as per international
standards and to identify determinants for better quality of thalassemia care.
Design: A cross sectional study was conducted using interview based structured
questionnaire, which was developed using standards of thalassemia care used by
International Thalassemia Foundation. Setting: Five healthcare facilities
catering to the needs of thalassemia patients in Rawalpindi and Islamabad,
Pakistan. Participants: Data were collected from 315 thalassemia patients from
May to August, 2016. Main outcome measure: Survey data on quality indicators.
Results: Results showed that almost half of thalassemia patients (48.5%) were
getting poor quality of care. On average patients were getting only 63.93% of
possible quality care for the disease. The most deficient quality area was
management of complications where patients were getting only 49.1% of possible
care. Better quality of care was likely to be received by those patients who were
educated, patients with educated fathers, those visiting private facilities and
those who were visiting facilities in Islamabad. Those with concomitant diseases
were also likely to receive better care. Conclusion: Quality of care provided to
thalassemia patients was well below the international standards for the care of
thalassemia. There is a need to take urgent action to improve quality of care in
the country.
PMID- 29346635
TI - A scoping study of frameworks for adapting public health evidence-based
interventions.
AB - Evidence-based public health translation of research to practice is essential to
improve the public's health. Dissemination and implementation researchers have
explored what happens once practitioners adopt evidence-based interventions
(EBIs) and have developed models and frameworks to describe the adaptation
process. This scoping study identified and summarized adaptation frameworks in
published reports and grey literature. We followed the recommended steps of a
scoping study: (a) identifying the research question; (b) identifying relevant
studies; (c) selecting studies; (d) charting the data; (e) collating,
summarizing, and reporting the results; and (f) consulting with experts. We
searched PubMed, PsycINFO, PsycNET, and CINAHL databases for articles referencing
adaptation frameworks for public health interventions in the published and gray
literature, and from reference lists of framework articles. Two reviewers
independently coded the frameworks and their steps and identified common steps.
We found 13 adaptation frameworks with 11 program adaptation steps: (a) assess
community, (b) understand the EBI(s), (c) select the EBI, (d) consult with
experts, (e) consult with stakeholders, (f) decide on needed adaptations, (g)
adapt the original EBI, (h) train staff, (i) test the adapted materials, (j)
implement the adapted EBI, and (k) evaluate. Eight of these steps were
recommended by more than five frameworks: #1-3, 6-7, and 9-11. This study is the
first to systematically identify, review, describe, and summarize frameworks for
adapting EBIs. It contributes to the literature by consolidating key steps in
program adaptation of EBIs and describing the associated tasks in each step.
PMID- 29346636
TI - Tuberculosis among the homeless in Chennai city, South India.
AB - Background: In India from a national perspective, the incidence/prevalence of
active tuberculosis (TB) among the homeless are unknown. Methods: Homeless
individuals, aged 15 years and above, were screened for TB by radiography and
smear examination in Chennai city. Results: 301 individuals were enrolled and
screened for TB; 8% (24/301) had chest symptoms; 5.6% (17/301) found X-ray
abnormalities. The overall prevalence of TB was 1661/100 000; prevalence of
culture-positive TB was 997/100 000 and smear-positive TB was 664/100 000
population. Conclusion: There is a need to address TB control among homeless
populations. The current pilot study showed that the prevalence of TB was
disproportionately high and there is a need for a larger study with an adequately
powered sample size.
PMID- 29346637
TI - Scleroderma renal crisis and cancer.
PMID- 29346638
TI - Standardized languages and notations for graphical modelling of patient care
processes: a systematic review.
AB - Purpose: The importance of working toward quality improvement in healthcare
implies an increasing interest in analysing, understanding and optimizing process
logic and sequences of activities embedded in healthcare processes. Their
graphical representation promotes faster learning, higher retention and better
compliance. The study identifies standardized graphical languages and notations
applied to patient care processes and investigates their usefulness in the
healthcare setting. Data sources: Peer-reviewed literature up to 19 May 2016.
Information complemented by a questionnaire sent to the authors of selected
studies. Study selection: Systematic review conducted in accordance with the
Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.
Data extraction: Five authors extracted results of selected studies. Results of
data synthesis: Ten articles met the inclusion criteria. One notation and
language for healthcare process modelling were identified with an application to
patient care processes: Business Process Model and Notation and Unified Modeling
LanguageTM. One of the authors of every selected study completed the
questionnaire. Users' comprehensibility and facilitation of inter-professional
analysis of processes have been recognized, in the filled in questionnaires, as
major strengths for process modelling in healthcare. Conclusion: Both the
notation and the language could increase the clarity of presentation thanks to
their visual properties, the capacity of easily managing macro and micro
scenarios, the possibility of clearly and precisely representing the process
logic. Both could increase guidelines/pathways applicability by representing
complex scenarios through charts and algorithms hence contributing to reduce
unjustified practice variations which negatively impact on quality of care and
patient safety.
PMID- 29346639
TI - Comparison of Dopamine D3 and D2 Receptor Occupancies by a Single Dose of
Blonanserin in Healthy Subjects: A Positron Emission Tomography Study With [11C]
(+)-PHNO.
AB - Background: Blockade of D3 receptor, a member of the dopamine D2-like receptor
family, has been suggested as a possible medication for schizophrenia.
Blonanserin has high affinity in vitro for D3 as well as D2 receptors. We
investigated whether a single dose of 12 mg blonanserin, which was within the
daily clinical dose range (i.e., 8-24 mg) for the treatment of schizophrenia,
occupies D3 as well as D2 receptors in healthy subjects. Methods: Six healthy
males (mean 35.7+/-7.6 years) received 2 positron emission tomography scans, the
first prior to taking blonanserin, and the second 2 hours after the
administration of a single dose of 12 mg blonanserin. Dopamine receptor
occupancies by blonanserin were evaluated by [11C]-(+)-PHNO. Results: Occupancy
of each region by 12 mg blonanserin was: caudate (range 64.3%-81.5%; mean+/-SD,
74.3+/-5.6%), putamen (range 60.4%-84.3%; mean+/-SD, 73.3%+/-8.2%), ventral
striatum (range 40.1%-88.2%; mean+/-SD, 60.8%+/-17.1%), globus pallidus (range
65.8%-87.6%; mean+/-SD, 75.7%+/-8.6%), and substantia nigra (range 56.0%-88.7%;
mean+/-SD, 72.4%+/-11.0%). Correlation analysis between plasma concentration of
blonanserin and receptor occupancy in D2-rich (caudate and putamen) and D3-rich
(globus pallidus and substantia nigra) regions showed that EC50 for D2-rich
region was 0.39 ng/mL (r=0.43) and EC50 for D3-rich region was 0.40 ng/mL
(r=0.79). Conclusions: A single dose of 12 mg blonanserin occupied D3 receptor to
the same degree as D2 receptor in vivo. Our results were consistent with previous
studies that reported that some of the pharmacological effect of blonanserin is
mediated via D3 receptor antagonism.
PMID- 29346640
TI - Preventive chemotherapy to control soil-transmitted helminthiasis averted more
than 500 000 DALYs in 2015.
AB - Background: Preventive chemotherapy (PC), the large-scale administration of
anthelminthics, is recommended by the World Health Organization (WHO) for the
control of soil-transmitted helminthiasis (STH). Since 2010, donated
anthelminthics for STH have boosted the implementation of PC programmes in
children, achieving global coverage of more than 60% in 2015. The WHO Global
Health Estimates attribute an annual loss of over 3.3 million disability-adjusted
life-years (DALYs) to STH. The aim of this study is to estimate the impact of PC
programmes on child morbidity. Method: We used data from the WHO Global Health
Estimates, national coverage data on PC and the results of an evaluation of the
impact of PC in 17 countries on morbidity previously conducted by our group.
Results: We estimated that the implementation of PC averted in 2015 over 44% of
the DALYs that would have been caused in children by STH without the control
intervention. A reduction in morbidity of over 75% is expected, if the global
target is reached in 2020. If the programme is subsequently maintained, morbidity
from STH will be almost totally removed by 2025. Conclusions: In endemic areas,
preventive chemotherapy provides a significant health benefit. We consider this
estimation potentially useful to evaluate the cost utility of the investment made
by several endemic countries on PC to control STH.
PMID- 29346641
TI - Uncovering behavioural diversity amongst high-strength Pseudomonas spp.
surfactants at the limit of liquid surface tension reduction.
AB - Bacterial biosurfactants have a wide range of biological functions and
biotechnological applications. Previous analyses had suggested a limit to their
reduction of aqueous liquid surface tensions (gammaMin), and here we confirm this
in an analysis of 25 Pseudomonas spp. strains isolated from soil which produce
high-strength surfactants that reduce surface tensions to 25.2 +/- 0.1-26.5 +/-
0.2 mN m-1 (the surface tension of sterile growth medium and pure water was 52.9
+/- 0.4 mN m-1 and 72.1 +/- 1.2 mN m-1, respectively). Comparisons of culture
supernatants produced using different growth media and semi-purified samples
indicate that the limit of 24.2-24.7 mN m-1 is not greatly influenced by culture
conditions, pH or NaCl concentrations. We have used foam, emulsion and oil
displacement behavioural assays as a simple and cost-effective proxy for in-depth
biochemical characterisation, and these suggest that there is significant
structural diversity amongst these surfactants that may reflect different
biological functions and offer new biotechnological opportunities. Finally, we
obtained a draft genome for the strain producing the highest strength surfactant,
and identified a cluster of non-ribosomal protein synthase genes that may produce
a cyclic lipopeptide (CLP)-like surfactant. Further investigation of this group
of related bacteria recovered from the same site will allow a better
understanding of the significance of the great variety of surfactants produced by
bacterial communities found in soil and elsewhere.
PMID- 29346642
TI - RNase 7 but not psoriasin nor sPLA2-IIA associates with Mycobacterium
tuberculosis during airway epithelial cell infection.
AB - Tuberculosis is a disease caused by Mycobacterium tuberculosis (Mtb). Innate
immunity is the first line of defense against Mtb and malfunctions in any of its
components are associated with the susceptibility to the disease. Epithelial
products such as host defense peptides (HDPs) are the first molecules produced to
counteract the infection. Although a wide variety of HDPs are produced by
epithelial cells only a few of them have been studied during Mtb infection. Here,
we assessed the expression and production of the HDPs psoriasin, secreted
phospholipases A2 (sPLA2-IIA) and Ribonuclease (RNase) 7 in airway epithelial
cells (NCI-H292), type II pneumocytes (A549 cells) and monocyte-derived
macrophages from human peripheral blood mononuclear cells and from the human cell
line THP1 after Mtb in vitro infection. Results show that psoriasin and sPLA2-IIA
were not induced by Mtb in any of the evaluated cells, while RNase 7 was
overexpressed in infected airway epithelial cells. Intracellular analysis by flow
cytometry demonstrated that the highest levels of RNase 7 were observed 6 h post
infection and the induction was dependent on direct interaction between airway
epithelial cells and Mtb. In addition, analysis by electron microscopy showed
that RNase 7 was capable of attaching to the cell wall of intracellular
mycobacteria. Our studies suggest that the induction of RNase 7 in response to
Mtb could have a role in anti-mycobacterial immunity, which needs to be studied
as an innate immune mechanism.
PMID- 29346643
TI - Genetic characterization of a VanG-type vancomycin-resistant Enterococcus faecium
clinical isolate.
AB - Objectives: To characterize, phenotypically and genotypically, the first
Enterococcus faecium clinical isolate harbouring a vanG operon. Methods: The
antibiotic resistance profile of E. faecium 16-346 was determined and its whole
genome sequenced using PacBio technology. Attempts to transfer vancomycin
resistance by filter mating were performed and the inducibility of expression of
the vanG operon was studied by reverse-transcription quantitative PCR (RT-qPCR)
in the presence or absence of subinhibitory concentrations of vancomycin.
Results: E. faecium 16-346 was resistant to rifampicin (MIC >4 mg/L),
erythromycin (MIC >4 mg/L), tetracycline (MIC >16 mg/L) and vancomycin (MIC 8
mg/L), but susceptible to teicoplanin (MIC 0.5 mg/L). The strain harboured the
vanG operon in its chromosome, integrated in a 45.5 kb putative mobile genetic
element, similar to that of Enterococcus faecalis BM4518. We were unable to
transfer vancomycin resistance from E. faecium 16-346 to E. faecium BM4107 and E.
faecalis JH2-2. Lastly, transcription of the vanG gene was inducible by
vancomycin. Conclusions: This is, to the best of our knowledge, the first report
of a VanG-type vancomycin-resistant strain of E. faecium. Despite the alarm
pulled because of the therapeutic problems caused by VRE, our work shows that new
resistant loci can still be found in E. faecium.
PMID- 29346644
TI - Genome-wide analysis of disease progression in age-related macular degeneration.
AB - Family- and population-based genetic studies have successfully identified
multiple disease-susceptibility loci for Age-related macular degeneration (AMD),
one of the first batch and most successful examples of genome-wide association
study. However, most genetic studies to date have focused on case-control studies
of late AMD (choroidal neovascularization or geographic atrophy). The genetic
influences on disease progression are largely unexplored. We assembled unique
resources to perform a genome-wide bivariate time-to-event analysis to test for
association of time-to-late-AMD with ~9 million variants on 2721 Caucasians from
a large multi-center randomized clinical trial, the Age-Related Eye Disease
Study. To our knowledge, this is the first genome-wide association study of
disease progression (bivariate survival outcome) in AMD genetic studies, thus
providing novel insights to AMD genetics. We used a robust Cox proportional
hazards model to appropriately account for between-eye correlation when analyzing
the progression time in the two eyes of each participant. We identified four
previously reported susceptibility loci showing genome-wide significant
association with AMD progression: ARMS2-HTRA1 (P = 8.1 * 10-43), CFH (P = 3.5 *
10-37), C2-CFB-SKIV2L (P = 8.1 * 10-10) and C3 (P = 1.2 * 10-9). Furthermore, we
detected association of rs58978565 near TNR (P = 2.3 * 10-8), rs28368872 near
ATF7IP2 (P = 2.9 * 10-8) and rs142450006 near MMP9 (P = 0.0006) with progression
to choroidal neovascularization but not geographic atrophy. Secondary analysis
limited to 34 reported risk variants revealed that LIPC and CTRB2-CTRB1 were also
associated with AMD progression (P < 0.0015). Our genome-wide analysis thus
expands the genetics in both development and progression of AMD and should assist
in early identification of high risk individuals.
PMID- 29346645
TI - Performance of an easy-to-use prediction model for renal patient survival: an
external validation study using data from the ERA-EDTA Registry.
AB - Background: An easy-to-use prediction model for long-term renal patient survival
based on only four predictors [age, primary renal disease, sex and therapy at 90
days after the start of renal replacement therapy (RRT)] has been developed in
The Netherlands. To assess the usability of this model for use in Europe, we
externally validated the model in 10 European countries. Methods: Data from the
European Renal Association-European Dialysis and Transplant Association (ERA
EDTA) Registry were used. Ten countries that reported individual patient data to
the registry on patients starting RRT in the period 1995-2005 were included.
Patients <16 years of age and/or with missing predictor variable data were
excluded. The external validation of the prediction model was evaluated for the
10- (primary endpoint), 5- and 3-year survival predictions by assessing the
calibration and discrimination outcomes. Results: We used a data set of 136 304
patients from 10 countries. The calibration in the large and calibration plots
for 10 deciles of predicted survival probabilities showed average differences of
1.5, 3.2 and 3.4% in observed versus predicted 10-, 5- and 3-year survival, with
some small variation on the country level. The concordance index, indicating the
discriminatory power of the model, was 0.71 in the complete ERA-EDTA Registry
cohort and varied according to country level between 0.70 and 0.75. Conclusions:
A prediction model for long-term renal patient survival developed in a single
country, based on only four easily available variables, has a comparably adequate
performance in a wide range of other European countries.
PMID- 29346647
TI - Resistance to Selected Pyrethroid Insecticides in the Malaria Mosquito, Anopheles
stephensi (Diptera: Culicidae), From Punjab, Pakistan.
AB - Pyrethroids are commonly used insecticides in malaria control programs; however,
insecticide resistance limits the benefits gained by using these insecticides. In
the present study, we assessed the resistance status for different pyrethroids of
the malaria mosquito vector, Anopheles stephensi Liston (Diptera: Culicidae), in
the Punjab province, Pakistan. Bioassays were conducted using diagnostic doses
following standard World Health Organization protocols: 0.05% lambda-cyhalothrin,
0.75% permethrin, 0.15% cyfluthrin, 0.05% deltamethrin, and 0.1% cypermethrin.
Field collected An. stephensi from four localities in Punjab (Khanewal, Multan,
Lodhran, and Bahawalpur) were reared in the laboratory, and non-blood-fed females
were used in the bioassays. An. stephensi from all the study sites except
Khanewal were found to be susceptible to permethrin and deltamethrin. Resistance
or potential resistance to cypermethrin, lambda-cyhalothrin and cyfluthrin was
observed from all the study sites. The median and 95% knockdown times (KDT50 and
KDT95) estimates for all the tested insecticides also showed similar responses.
In conclusion, the study revealed resistance to selected pyrethroids in An.
stephensi from some parts of Punjab, Pakistan, underscoring the need to devise a
resistance management strategy for effective control of this important malaria
vector.
PMID- 29346646
TI - The Evolutionary History of Nebraska Deer Mice: Local Adaptation in the Face of
Strong Gene Flow.
AB - The interplay of gene flow, genetic drift, and local selective pressure is a
dynamic process that has been well studied from a theoretical perspective over
the last century. Wright and Haldane laid the foundation for expectations under
an island-continent model, demonstrating that an island-specific beneficial
allele may be maintained locally if the selection coefficient is larger than the
rate of migration of the ancestral allele from the continent. Subsequent
extensions of this model have provided considerably more insight. Yet, connecting
theoretical results with empirical data has proven challenging, owing to a lack
of information on the relationship between genotype, phenotype, and fitness.
Here, we examine the demographic and selective history of deer mice in and around
the Nebraska Sand Hills, a system in which variation at the Agouti locus affects
cryptic coloration that in turn affects the survival of mice in their local
habitat. We first genotyped 250 individuals from 11 sites along a transect
spanning the Sand Hills at 660,000 single nucleotide polymorphisms across the
genome. Using these genomic data, we found that deer mice first colonized the
Sand Hills following the last glacial period. Subsequent high rates of gene flow
have served to homogenize the majority of the genome between populations on and
off the Sand Hills, with the exception of the Agouti pigmentation locus.
Furthermore, mutations at this locus are strongly associated with the pigment
traits that are strongly correlated with local soil coloration and thus
responsible for cryptic coloration.
PMID- 29346648
TI - EsrB negatively regulates expression of the glutamine sythetase GlnA in the fish
pathogen Edwardsiella piscicida.
AB - Edwardsiella piscicida is a gram-negative bacterial pathogen invading a wide
range of fish species. Response regulator EsrB is essential for the activation of
type III and type VI secretion systems (T3/T6SS). In this study, proteomes of the
wild-type E. piscicida EIB202 and DeltaesrB mutant strains were compared to
identify the regulon components of EsrB cultured in DMEM allowing T3/T6SS
expression. As a result, 19 proteins showed different expression, which were
identified to be associated with T3/T6SS, related to amino acid transport and
metabolism, and energy production. Particularly, GlnA, a glutamine synthetase
essential for ammonia assimilation and glutamine biosynthesis from glutamate, was
found to be regulated negatively by EsrB. Moreover, GlnA affected bacterial
growth in vitro and bacterial colonization in vivo. Collectively, our results
indicated that EsrB plays important roles in regulating the expression of
metabolic pathways and virulence genes, including glutamine biosynthesis in E.
piscicida during infection.
PMID- 29346649
TI - Endothelial function in rheumatoid arthritis.
AB - Background: Rheumatoid arthritis (RA) patients are at higher risk of accelerated
atherosclerosis. Aims: To assess endothelial dysfunction in RA to find a possible
mechanistic pathway that will explain the clinical phenomenon. Methods: A
prospective study recruited 44 RA patients with an active long standing (>12
months) disease. All underwent a detailed assessment of disease activity. To
estimate the endothelial function the brachial artery method was performed,
measuring flow mediated diameter percent (FMD%) change. Clustering analyses
(hierarchical and k-means) were performed. Patients were compared to healthy
subjects. Results: Forty four RA patients (54.42 +/- 11.14 years, females
(72.7%)) with co-morbidities (70.5%), not taking tumor necrosis factor-blockers
or disease modifying anti rheumatic drugs (63.6%). Only 6 (13.6%) had a normal
endothelial function. Hierarchical and k-means clustering techniques showed
statistically significant differences among the three clusters concerning disease
activity score-28 (DAS-28)- erythrocyte sedimentation rate (ESR) (P = 0.000), DAS
28- C-reactive protein (CRP; P = 0.001), clinical disease activity index (P =
0.002), simplified disease activity index (P = 0.001), ESR (P = 0.000), (CRP) (P
= 0.003) and FMD% (P = 0.009). The group with the highest FMD% values exhibited
the lowest clinical scores and laboratory parameters. Patients with the lowest
FMD% values co-clustered with subjects with positive but low FMD% changes and
elevated clinical and laboratory parameters. Conclusions: Our study confirmed the
feasibility of exploiting endothelial function in clinical practice as an early
predictor of atherosclerosis in RA patients.
PMID- 29346650
TI - Persistence of Zika Virus After Birth: Clinical, Virological, Neuroimaging, and
Neuropathological Documentation in a 5-Month Infant With Congenital Zika
Syndrome.
AB - During the Zika epidemic in Brazil, a baby was born at term with microcephaly and
arthrogryposis. The mother had Zika symptoms at 10 weeks of gestation. At 17
weeks, ultrasound showed cerebral malformation and ventriculomegaly. At 24 weeks,
the amniotic fluid contained ZIKV RNA and at birth, placenta and maternal blood
were also positive using RT-qPCR. At birth the baby urine contained ZIKV RNA,
whereas CSF at birth and urine at 17 days did not. Seizures started at 6 days.
EEG was abnormal and CT scan showed cerebral atrophy, calcifications,
lissencephaly, ventriculomegaly, and cerebellar hypoplasia. Bacterial sepsis at 2
months was treated. A sudden increase in head circumference occurred at 4 months
necessitating ventricle-peritoneal shunt placement. At 5 months, the infant died
with sepsis due to bacterial meningitis. Neuropathological findings were as
severe as some of those found in neonates who died soon after birth, including
hydrocephalus, destructive lesions/calcification, gliosis, abnormal neuronal
migration, dysmaturation of nerve cells, hypomyelination, loss of descending
axons, and spinal motor neurons. ZIKV RNA was detected only in frozen brain
tissue using RT-qPCR, but infected cells were not detected by in situ
hybridization. Progressive gliosis and microgliosis in the midbrain may have
contributed to aqueduct compression and subsequent hydrocephalus. The etiology of
progressive disease after in utero infection is not clear and requires
investigation.
PMID- 29346652
TI - Toward rational antibody design: recent advancements in molecular dynamics
simulations.
AB - Because antibodies have become an important therapeutic tool, rational antibody
design is a challenging issue involving various science and technology fields.
From the computational aspect, many types of design-assist methods have been
developed, but their accuracy is not fully satisfactory. Because of recent
advancements in computational power, molecular dynamics (MD) simulation has
become a helpful tool to trace the motion of proteins and to characterize their
properties. Thus, MD simulation has been applied to various systems involving
antigen-antibody complexes and has been shown to provide accurate insight into
antigen-antibody interactions and dynamics at an atomic resolution. Therefore, it
is highly possible that MD simulation will play several roles complementing the
conventional antibody design. In this review, we address several important
features of MD simulation in the context of rational antibody design.
PMID- 29346651
TI - Bipartite Network Analysis of Gene Sharings in the Microbial World.
AB - Extensive microbial gene flows affect how we understand virology, microbiology,
medical sciences, genetic modification, and evolutionary biology. Phylogenies
only provide a narrow view of these gene flows: plasmids and viruses, lacking
core genes, cannot be attached to cellular life on phylogenetic trees. Yet
viruses and plasmids have a major impact on cellular evolution, affecting both
the gene content and the dynamics of microbial communities. Using bipartite
graphs that connect up to 149,000 clusters of homologous genes with 8,217 related
and unrelated genomes, we can in particular show patterns of gene sharing that do
not map neatly with the organismal phylogeny. Homologous genes are recycled by
lateral gene transfer, and multiple copies of homologous genes are carried by
otherwise completely unrelated (and possibly nested) genomes, that is, viruses,
plasmids and prokaryotes. When a homologous gene is present on at least one
plasmid or virus and at least one chromosome, a process of "gene
externalization," affected by a postprocessed selected functional bias, takes
place, especially in Bacteria. Bipartite graphs give us a view of vertical and
horizontal gene flow beyond classic taxonomy on a single very large, analytically
tractable, graph that goes beyond the cellular Web of Life.
PMID- 29346653
TI - Emergence of acute/subacute infant-juvenile paracoccidioidomycosis in Northeast
Argentina: Effect of climatic and anthropogenic changes?
AB - Argentina has two endemic areas of paracoccidioidomycosis (PCM). Bordering
Paraguay and Brazil, Northeast Argentina (NEA) comprises the area with the
highest incidence where the chronic adult clinical form has historically been
reported. Juvenile form in children and adolescents is rare in this area since
only one case was reported in the last 10 years. Despite this, between 2010 and
2012, several cases of acute/subacute clinical forms in children aged 10 to 16
(median 12) were detected. In the last decade, the NEA region has been exposed to
ecological variations as consequences of certain climatic and anthropogenic
changes, including El Nino-Southern Oscillation phenomenon during 2009, and
deforestation. The region has also suffered from the significant ecological
effects of the construction of one of the biggest hydroelectric dams of South
America. This study aims to describe clinical and epidemiological aspects of
acute/subacute PCM cases detected in children from NEA and to discuss climatic
and anthropogenic changes as possible contributing factors in the emergence of
this disease in children. This acute/subacute PCM cluster was characterized by
severe disseminated and aggressive presentations to localized form, with a high
spectrum of clinical manifestations uncommonly observed. Due to the lack of
experience in acute/subacute PCM in children in the studied area and the atypical
clinical manifestations observed, the diagnosis was delayed. In order to avoid
misdiagnosis, a higher level of suspicion is now required in NEA and countries
bordering the southern part of the endemic area, which are affected by the
changes discussed in this article.
PMID- 29346654
TI - Evaluation of system mapping approaches in identifying patient safety risks.
AB - Objective: While many system mapping approaches (SMAs) have been broadly used in
safety-critical industries, few have so far been employed in the healthcare field
to assist in the identification of patient safety risks. In this study, we
evaluated a set of system modelling approaches to assess their potential
contribution to the identification of risks affecting patient safety. The aim was
to gain a greater understanding of the practical application of system modelling
approaches with the help of the risk categorization framework developed in this
study. Setting: We conducted this study in a newly established Adult Attention
Deficit Hyperactivity Disorder (ADHD) service at Cambridge and Peterborough
Foundation Trust. Study participants: Eight key stakeholders of the chosen
service, including clinicians, managers and administrative staff, were
individually asked to evaluate a set of pre-defined six SMAs according to their
usefulness in identifying patient safety risks through interview-based
questionnaires. Results: It was found that each SMA could be useful in the chosen
healthcare service in different ways. Further, specific types of diagrams were
selected by stakeholders as more useful than others in identifying different
sources of risks within the given system. Conclusions: The results of the
evaluation showed that the system diagram is the most useful SMA in risk
identification within the given system, while limited time, resources and
experience of stakeholders with SMAs may present possible obstacles for their
potential use in the healthcare field in future.
PMID- 29346656
TI - Host responses to intestinal nematodes.
AB - Helminth infection remains common in developing countries, where residents who
suffer from the consequences of such infections can develop serious physical and
mental disorders and often persist in the face of serious economic problems.
Intestinal nematode infection induces the development of Th2-type immune
responses including the B-cell IgE response; additionally, this infection induces
an increase in the numbers and activation of various types of effector cells,
such as mast cells, eosinophils and basophils, as well as the induction of goblet
cell hyperplasia, anti-microbial peptide production and smooth-muscle
contraction, all of which contribute to expel nematodes. Innate immunity is
important in efforts to eliminate helminth infection; cytokines, including IL-25,
IL-33 and thymic stromal lymphopoietin, which are products of epithelial cells
and mast cells, induce Th2 cells and group 2 innate lymphoid cells to proliferate
and produce Th2 cytokines. Nematodes also facilitate chronic infection by
suppression of immune reactions through an increased number of Treg cells.
Immunosuppression by parasite infection may ultimately be beneficial for the host
animals; indeed, a negative correlation has been found between parasite infection
and the prevalence of inflammatory disease in humans.
PMID- 29346655
TI - Does the Additional Component of Calf Circumference Refine Metabolic Syndrome in
Correlating With Cardiovascular Risk?
AB - Context: Calf circumference (CC) was a useful anthropometric tool, but there was
limited study on the effect of CC on metabolic syndrome (MetS) for cardiovascular
risk. Objective: The objective of our study was to determine whether adding CC as
a component of MetS refined correlating MetS with cardiovascular, all-cause, and
cancer mortality risks. Design, Setting, Patients, and Interventions: From the
National Health and Nutrition Examination Survey data set for 1999 through 2002,
we analyzed four types of MetS: (1) increased waist circumference and two or more
of four MetS components (WaistMetS); (2) decreased CC and two or more of four
MetS components (CalfMetS); (3) increased waist-to-calf ratio and two or more of
four MetS components (WCRMetS); and (4) decreased CC and three or more of five
MetS components (CC+MetS). Primary Outcome Measure: The cause-specific hazard
ratios were measured as categorized by the four types of MetS. Results: For
cardiovascular mortality, the adjusted hazard ratios for WaistMetS, CalfMetS,
WCRMetS, and CC+MetS were 1.867, 1.871, 1.949, and 2.306, respectively (all P <
0.001). Notably, CalfMetS showed the strongest positive correlation with serum C
reactive protein levels, and WCRMetS had the strongest positive relationship with
homeostasis model assessment of insulin resistance. Conclusions: Adding CC to the
components of MetS correlated with higher cardiovascular and all-cause mortality
risk than the traditional definition of MetS.
PMID- 29346657
TI - Perspectives on Queer Music Therapy: A Qualitative Analysis of Music Therapists'
Reactions to Radically Inclusive Practice.
AB - Background: The queer music therapy model was designed by Bain, Grzanka, and
Crowe in 2016 as a novel therapeutic approach to affirm and empower LGBTQ+
identity through music. No data have been generated on how this model might
actually be implemented, or the strengths and limitations of the model according
to music therapy professionals. Objective: The purpose of this study was to build
on Bain and colleagues' work by collecting music therapists' perspectives on
queer music therapy and using these data to critically evaluate the model.
Methods: Semi-structured qualitative interviews were conducted with twelve music
therapists who identify as LGBTQ+ or have experience working with LGBTQ+ clients.
Participants were prompted to discuss their music therapy backgrounds,
experiences with LGBTQ+ clients, and reactions to the queer music therapy model.
Interviews were analyzed using a critical discourse analysis approach. Results:
The qualitative findings revealed major strengths of the queer music therapy
model and ways in which it could be improved by attending to: (a) the structural
limitations of the music therapy discipline, including the demographic
composition of the field and lack of critical perspectives in music therapy
training; and (b) intersectional considerations of ageism and ableism within
diverse LGBTQ+ populations. Conclusions: Queer music therapy has positive
implications for future work with LGBTQ+ individuals, but it must more
substantively integrate intersectionality theory to serve a diverse range of
LGBTQ+ clients. Further, it must critically attend to the structural limitations
of the music therapy discipline itself.
PMID- 29346658
TI - Potential for diet to prevent and remediate cognitive deficits in neurological
disorders.
AB - The pathophysiology of many neurological disorders involves oxidative stress,
neuroinflammation, and mitochondrial dysfunction. There is now substantial
evidence that diet can decrease these forms of pathophysiology, and an emerging
body of literature relatedly suggests that diet can also prevent or even
remediate the cognitive deficits observed in neurological disorders that exhibit
such pathology (eg, Alzheimer's disease, multiple sclerosis, age-related
cognitive decline, epilepsy). The current review summarizes the emerging evidence
in relation to whole diets prominent in the scientific literature-ketogenic,
caloric restriction, high polyphenol, and Mediterranean diets-and provides a
discussion of the possible underlying neurophysiological mechanisms.
PMID- 29346659
TI - Case Report: Facial Nerve Bifurcation Noted During Resection of Vestibular
Schwannoma.
AB - BACKGROUND AND IMPORTANCE: Resection of cerebellopontine angle tumors is
challenging because the proximity of the facial nerve puts it at risk of
inadvertent injury and subsequent dysfunction. It is critical to consider
variations in anatomy and be aware of the potential deviations in the course of
the nerve in order to avoid damage. CLINICAL PRESENTATION: We present a case of a
facial nerve bifurcation identified during resection of a vestibular schwannoma.
CONCLUSION: This is the only reported case of proximal facial nerve bifurcation.
We review what is known about variations in proximal facial nerve anatomy, the
rates of facial nerve injury after schwannoma resection, and the importance of
neuromonitoring in identifying the nerve and predicting function postoperatively.
Ultimately, understanding possible anatomic variations in the nerve is critical
to minimize iatrogenic injury during surgery.
PMID- 29346660
TI - Herpes zoster and Hutchinson's sign.
PMID- 29346661
TI - The role of healthcare and education systems in co-occurrence of health risk
behaviours in 27 European countries.
AB - Background: Contextual factors play an important role in health and related
behaviours. This study aims to examine the association of co-occurrence of five
health-risk behaviours with healthcare and education contextual factors using
nationally representative samples from 27 European countries. Methods: Data were
from Eurobarometer 72.3, 2009. The outcome was a count variable ranging from 0 to
5 indicating co-occurrence of five health-risk behaviours, namely smoking,
excessive alcohol consumption, non-frequent fresh fruit consumption, physical
inactivity and non-dental check-ups. Public expenditures on healthcare and
education as a percentage of GDP and quality of healthcare and education at a
country-level were used as contextual factors. A set of multilevel Poisson
regression models were conducted to examine the associations between co
occurrence of health-risk behaviours and each of the contextual factors
considering age, gender, marital status, urbanisation, individual socioeconomic
positions (education, subjective social status or difficulty in paying bills) and
GDP per capita. Results: The total population was 23 842. Greater expenditures on
healthcare and education, and better quality of healthcare systems had negative
associations with co-occurrence of health-risk behaviours in the model adjusted
for all individual demographic indicators. However, statistical significance
disappeared after adjusting for socioeconomic indicators and GDP per capita.
Conclusion: While the study highlights the importance of developing high-quality
healthcare and education systems generously supported by public fund in relation
to co-occurrence of health-risk behaviours, the influence of contextual factors
in adopting health-related behaviours is probably attenuated by individual
socioeconomic factors.
PMID- 29346662
TI - Shifting determinants of health inequalities in unstable times: Portugal as a
case study.
AB - Background: We explore how health inequalities (HI) changed in Portugal over the
last decade, considering it is one of the most unequal European countries and has
gone through major economic changes. We describe how inequalities in limitations
changed considering different socioeconomic determinants, in order to understand
what drove changes in HI. Methods: We used cross-sectional waves from the
European Survey on Income and Living Conditions database to determine how
inequalities in health limitations changed between 2004 and 2014 in Portugal in
residents aged 16 years and over. We calculated prevalence estimates of
limitations and differences between income terciles, the concentration index for
each year and its decomposition and multiple logistic regressions to estimate the
association between socioeconomic determinants and limitations. Results: The
prevalence of health limitations increased in Portugal since 2004, especially
after 2010, from 35 to 47%. But the difference between top and bottom income
terciles decreased from 23 to 10 percentage points, as richer people experienced
a steeper increase. This was driven by an increase in prevalence among
economically active people, who, from 2011 onwards, had more limitations (OR and
95% CI were 2.42 [2.13-2.75] in 2004 and 0.71 [0.65-0.78] in 2014). Conclusion:
These results suggest worsening health in Portugal in the last decade, possibly
connected to periods of economic instability. However, absolute HI decreased
considerably in the same period. We discuss the possible role of diverse
adaptation capacity of socioeconomic groups, and of high emigration rates of
young, healthier people, reflecting another side of the 'migrant health effect'.
PMID- 29346664
TI - Challenges for prevention research.
PMID- 29346663
TI - Resident participation in neighbourhood audit tools - a scoping review.
AB - Background: Healthy urban environments require careful planning and a testing of
environmental quality that goes beyond statutory requirements. Moreover, it
requires the inclusion of resident views, perceptions and experiences that help
deepen the understanding of local (public health) problems. To facilitate this,
neighbourhoods should be mapped in a way that is relevant to them. One way to do
this is participative neighbourhood auditing. This paper provides an insight into
availability and characteristics of participatory neighbourhood audit
instruments. Methods: A scoping review in scientific and grey literature,
consisting of the following steps: literature search, identification and
selection of relevant audit instruments, data extraction and data charting
(including a work meeting to discuss outputs), reporting. Results: In total, 13
participatory instruments were identified. The role of residents in most
instruments was as 'data collectors'; only few instruments included residents in
other audit activities like problem definition or analysis of data. The
instruments identified focus mainly on physical, not social, neighbourhood
characteristics. Paper forms containing closed-ended questions or scales were the
most often applied registration method. Conclusions: The results show that
neighbourhood auditing could be improved by including social aspects in the audit
tools. They also show that the role of residents in neighbourhood auditing is
limited; however, little is known about how their engagement takes place in
practice. Developers of new instruments need to balance not only social and
physical aspects, but also resident engagement and scientific robustness.
Technologies like mobile applications pose new opportunities for participative
approaches in neighbourhood auditing.
PMID- 29346665
TI - Moving towards compulsory vaccination: the Italian experience.
PMID- 29346666
TI - Gypsy, Roma and Traveller access to and engagement with health services: a
systematic review.
AB - Background: Gypsy, Roma and Traveller people represent the most disadvantaged
minority groups in Europe, having the poorest health outcomes. This systematic
review addressed the question of how Gypsy, Roma and Traveller people access
healthcare and what are the best ways to enhance their engagement with health
services. Methods: Searches were conducted in 21 electronic databases
complemented by a focussed Google search. Studies were included if they had
sufficient focus on Gypsy, Roma or Traveller populations; reported data pertinent
to healthcare service use or engagement and were published in English from 2000
to 2015. Study findings were analyzed thematically and a narrative synthesis
reported. Results: Ninety-nine studies from 32 countries were included, covering
a range of health services. Nearly one-half of the presented findings related to
primary healthcare services. Reported barriers to health service usage related to
organisation of health systems, discrimination, culture and language, health
literacy, service-user attributes and economic barriers. Promising engagement
strategies included specialist roles, outreach services, dedicated services,
raising health awareness, handheld records, training for staff and collaborative
working. Conclusion: This review provides evidence that Gypsy, Roma and Traveller
populations across Europe struggle to exercise their right to healthcare on
account of multiple barriers; and related to other determinants of disadvantage
such as low literacy levels and experiences of discrimination. Some promising
strategies to overcome barriers were reported but the evidence is weak;
therefore, rigorous evaluations of interventions to improve access to and
engagement with health services for Gypsy, Roma and Traveller people are needed.
PMID- 29346667
TI - The Results of Hemoglobin Variant Analysis in Patients Revealing Microcytic
Erythrocytosis on Complete Blood Count.
AB - Background: Microcytic erythrocytosis is an underrecognized and underevaluated
complete blood count (CBC) finding. The literature pertaining to the
determination of its etiology specifically by hemoglobin variant analysis is
limited. Methods: We performed hemoglobin variant analysis by high performance
liquid chromatography on 137 patients who revealed microcytic erythrocytosis on
CBC, and reviewed the results for the diagnosis of hemoglobin-associated
disorders. Results: A diagnosis of thalassemia trait and/or a hemoglobinopathy
was established in 93 of 137 (67.9%) patients. Amongst these, beta-thalassemia
trait topped the list with 69 cases (74.1%), followed by hereditary persistence
of fetal hemoglobin with 5 cases (5.5%), Hemoglobin E disease with 4 cases
(4.3%), and ?/beta-thalassemia with 2 cases (2.1%). Compound heterozygous
conditions with 1 or more hemoglobinopathies and/or thalassemias were diagnosed
in 13 cases (14.0%). Abnormal hemoglobins in the compound heterozygosity group
included C, S, HPFH, and 2 unknowns. Conclusion: Hemoglobin variant analysis
provided a very high positive yield in determining the etiology of microcytic
erythrocytosis.
PMID- 29346669
TI - Regulation of mitotic recombination between DNA repeats in centromeres.
PMID- 29346668
TI - RAD51 and RTEL1 compensate telomere loss in the absence of telomerase.
AB - Replicative erosion of telomeres is naturally compensated by telomerase and
studies in yeast and vertebrates show that homologous recombination can
compensate for the absence of telomerase. We show that RAD51 protein, which
catalyzes the key strand-invasion step of homologous recombination, is localized
at Arabidopsis telomeres in absence of telomerase. Blocking the strand-transfer
activity of the RAD51 in telomerase mutant plants results in a strikingly earlier
onset of developmental defects, accompanied by increased numbers of end-to-end
chromosome fusions. Imposing replication stress through knockout of RNaseH2
increases numbers of chromosome fusions and reduces the survival of these plants
deficient for telomerase and homologous recombination. This finding suggests that
RAD51-dependent homologous recombination acts as an essential backup to the
telomerase for compensation of replicative telomere loss to ensure genome
stability. Furthermore, we show that this positive role of RAD51 in telomere
stability is dependent on the RTEL1 helicase. We propose that a RAD51 dependent
break-induced replication process is activated in cells lacking telomerase
activity, with RTEL1 responsible for D-loop dissolution after telomere
replication.
PMID- 29346670
TI - SCOPING ANALYSIS OF MATERIAL ACTIVATION AT A BORON NEUTRON CAPTURE THERAPY
FACILITY BASED ON THE Be(p,xn) REACTION WITH 30 MeV PROTONS.
AB - Material activation assessment of a proposed accelerator-based boron neutron
capture therapy facility was performed using the FLUKA Monte Carlo code to
quantify the magnitude of the problem in terms of the isotope inventories,
induced activities, and residual dose rates. Two simplified operation scenarios
were considered: a 30-min proton bombardment to simulate a typical session of
patient treatment and a long-term 1 year continuous operation to estimate the
accumulation of long-lived radionuclides. Following the generation and transport
of decay radiation, the space- and time-dependent inventories of induced
radionuclides in materials and residual dose rates after shutdown were obtained.
The predicted results were compared with the corresponding regulatory limits.
Moreover, the effectiveness of various measures to reduce the impact of material
activation was demonstrated.
PMID- 29346671
TI - Hematological Analysis in Thai Samples With Deletional and Nondeletional HbH
Diseases.
AB - Objectives: To compare hematological parameters between deletional and
nondeletional HbH diseases, and to investigate the correlation between HbH levels
and hematological parameters within these 2 groups. Methods: Samples of 43
deletional HbH diseases, which included 39 --SEA/-alpha3.7, 4 - -SEA/-alpha4.2,
and 22 nondeletional HbH diseases (- -SEA/alphacsalpha), were used in this study.
Correlations between HbH levels and hematological parameters within these 2
groups were analyzed. Results: The deletional HbH disease had higher levels of
RBC counts, total Hb, pack cell volume (PCV), mean corpuscular Hb (MCH), mean
corpuscular Hb concentration (MCHC), HbA, and HbA2 than did the nondeletional HbH
disease. A negative correlation between HbH and RBC counts was detected in the
group of deletional HbH disease, while a positive correlation between HbH and RBC
counts, total Hb, and PCV was found in the group of nondeletional HbH disease.
Conclusions: These results reflected that samples with nondeletional HbH showed
more anemic features than those with the deletional HbH.
PMID- 29346672
TI - Learning to Live With Schizoaffective Disorder: A Transformative Journey Toward
Recovery.
PMID- 29346673
TI - Commentary on "The Potential of Cannabidiol Treatment for Cannabis Users With
Recent-Onset Psychosis".
PMID- 29346674
TI - Integrating Research Techniques to Improve Quality and Safety in the
Preanalytical Phase.
AB - Background: Reducing errors in the preanalytical phase is difficult, which
suggests the issue may be multidimensional. As such, qualitative research may be
truly innovative in this context. Method: We carried out a descriptive study
using a qualitative method incorporating 4 focus groups. Data analysis followed
the principles of Grounded Theory. Results: We queried in each of the 4 focus
groups collectively to identify weaknesses in the system. Those weaknesses that
were most cited were logistics, coupled with uneven compliance with regulations.
Conclusion: All 4 focus groups mapped out directives for future work, so that
regulatory aspects, process management, communication and resources could be
identified as key areas where error reduction is critical.
PMID- 29346675
TI - In search of the best xenogeneic material for a paediatric conduit: an
experimental study.
AB - OBJECTIVES: The development of calcification-resistant bioprosthetic materials is
a very important challenge for paediatric surgery. The subcutaneous implantation
in rats is the well-known first-stage model for this kind of research. Using this
model, we aimed to compare calcification of the porcine aortic wall and bovine
pericardium and jugular vein wall cross-linked with glutaraldehyde (GA) and
ethylene glycol diglycidyl ether (DE). We also determined the efficacy of DE
preserved tissue modification with 2-(2-carboxyethylamino)ethylidene-1,1
bisphosphonic acid (CEABA). METHODS: Three groups of each biomaterial were
evaluated: GA-treated, DE-treated and DE + CEABA-treated. The microstructure of
non-implanted biomaterials was assessed by light microscopy after Picro Mallory
staining; the phosphorus content of the DE and DE + CEABA samples was assessed by
atomic emission spectrometry. Samples were implanted subcutaneously into young
rats for 10 and 60 days. The explant end-point included quantitative
calcification assessment by atomic absorption spectrophotometry and light
microscopy examination after von Kossa staining. RESULTS: All GA-treated
biomaterials had a high calcium-binding capacity (>100 MUg/mg dry tissue). DE
preservation decreased the vein wall and pericardium calcium content by 4- and 40
fold, respectively, but was ineffective for the aortic wall. The calculated CEABA
content was almost equal in the vein wall and pericardium (17.7 and 18.5 MUM/g)
and slightly less in the aortic wall (15 MUM/g) (P = 0.011). CEABA effectively
reduced mineralization in the DE aortic wall and DE pericardium to 10.1 (7.8
21.1) and 0.95 (0.57-1.38) MUg/mg but had no effect in the DE vein wall.
Mineralization in the GA- and DE-treated aortic and vein walls was predominantly
associated with elastin. CEABA modification decreased elastin calcification but
did not block it completely. CONCLUSIONS: Each xenogeneic material requires
individual anticalcification strategy. DE + CEABA pretreatment demonstrates a
high mineralization-blocking efficacy for the bovine pericardium and should be
employed to further develop the paediatric pericardial conduit. Aortic wall
calcification cannot be blocked completely using this strategy.
PMID- 29346676
TI - Familial hypercholesterolemia: xanthelasma, corneal arcus and tendon xanthomas,
only in severe forms.
PMID- 29346677
TI - Anatomical explanations for acute depressions in radial pattern of axial sap flow
in two diffuse-porous mangrove species: implications for water use.
AB - Mangrove species have developed uniquely efficient water-use strategies in order
to survive in highly saline and anaerobic environments. Herein, we estimated the
stand water use of two diffuse-porous mangrove species of the same age,
Sonneratia apetala Buch. Ham and Sonneratia caseolaris (L.) Engl., growing in a
similar intertidal environment. Specifically, to investigate the radial patterns
of axial sap flow density (Js) and understand the anatomical traits associated
with them, we measured axial sap flow density in situ together with
micromorphological observations. A significant decrease of Js was observed for
both species. This result was accompanied by the corresponding observations of
wood structure and blockages in xylem sapwood, which appeared to influence and,
hence, explained the acute radial reductions of axial sap flow in the stems of
both species. However, higher radial resistance in sapwood of S. caseolaris
caused a steeper decline of Js radially when compared with S. apetala, thus
explaining the latter's more efficient use of water. Without first considering
acute reductions in Js into the sapwood from the outer bark, a total of ~55% and
51% of water use would have been overestimated, corresponding to average
discrepancies in stand water use of 5.6 mm day-1 for S. apetala trees and 2.5 mm
day-1 for S. caseolaris trees. This suggests that measuring radial pattern of Js
is a critical factor in determining whole-tree or stand water use.
PMID- 29346678
TI - Case study of an adaptation and implementation of a Diabetes Prevention Program
for individuals with serious mental illness.
AB - The Diabetes Prevention Program (DPP) is an evidence-based lifestyle intervention
developed to decrease the risk for type 2 diabetes and promote weight loss in
individuals at risk for diabetes. Individuals with serious mental illness have a
greater risk for developing diabetes compared with the general population. In
this article, the authors provide a detailed description of the adaptation
process of the DPP for individuals with serious mental illness (DPP-SMI). The
adaptation process was based on a cultural adaptation framework for modifying
evidence-based interventions. To assess the effectiveness of the DPP-SMI, 11
individuals from a community mental health residential agency completed a 22
session pilot study of the adapted program and provided physiological measures
before and after the intervention. As primary outcomes, participants were
expected to report decreased body weight and increased physical activity per
week. Completers had an average weight loss of 19 lbs (8%) and their physical
activity increased from 161 to 405 min per week. These preliminary results
together with participants' feedback informed further refinement of the DPP-SMI.
This case study supports that individuals with serious mental illness can benefit
from the DPP-SMI, which is tailored to meet the unique needs of this population
group.
PMID- 29346679
TI - Risk stratification in Takotsubo syndrome: a role of mitral annular plane
systolic excursion.
AB - Aim: Takotsubo syndrome (TTS) patients have a higher mortality rate than the
general population. Our study was conducted to determine the short- and long-term
outcome of TTS patients associated with a significantly compromised mitral
annular plane systolic excursion (MAPSE) on hospital admission. Methods and
results: Our institutional database constituted a collective of 53 patients
diagnosed with TTS between 2003 and 2016. The patients were classified into two
groups based on the MAPSE, with those presenting with an MAPSE <1 cm on admission
categorized into one group (n = 20, 38%) and those presenting with MAPSE >=1 cm
(n = 33, 62%) categorized into another group. Preliminary results indicated that
patients with an MAPSE < 1 cm had a greater risk of developing thromboembolic
events. The long-term mortality was significantly higher in TTS patients with an
MAPSE < 1 cm. In the multivariate Cox regression analysis, cardiogenic shock
(hazard ratio 3.5; 95% confidence interval: 1.2-10.7; P = 0.02) and MAPSE < 1 cm
(hazard ratio 5.1; 95% confidence interval: 1.3-19.2; P = 0.01) figured as
independent predictors of the mortality. Conclusion: Although the short-term
mortality rates among TTS patients diagnosed with a reduced MAPSE on admission
were as similar as without reduced MAPSE, the long-term mortality rates among TTS
patients diagnosed with a reduced MAPSE on admission were significantly higher.
There is an urgent need for randomized trials, which could help define uniform
clinical management strategies for high-risk TTS patients.
PMID- 29346680
TI - Conjunctival petechiae and infective endocarditis.
PMID- 29346681
TI - Optimal number and sizes of the doses in fractionated radiotherapy according to
the LQ model.
AB - We address a non-linear programming problem to find the optimal scheme of dose
fractionation in cancer radiotherapy. Using the LQ model to represent the
response to radiation of tumour and normal tissues, we formulate a constrained
non-linear optimization problem in terms of the variables number and sizes of the
dose fractions. Quadratic constraints are imposed to guarantee that the damages
to the early and late responding normal tissues do not exceed assigned tolerable
levels. Linear constraints are set to limit the size of the daily doses. The
optimal solutions are found in two steps: i) analytical determination of the
optimal sizes of the fractional doses for a fixed, but arbitrary number of
fractions n; ii) numerical simulation of a sequence of the previous optima for n
increasing, and for specific tumour classes. We prove the existence of a finite
upper bound for the optimal number of fractions. So, the optimum with respect to
n is found by means of a finite number of comparisons amongst the optimal values
of the objective function at the first step. In the numerical simulations, the
radiosensitivity and repopulation parameters of the normal tissue are fixed,
while we investigate the behaviour of the optimal solution for wide variations of
the tumour parameters, relating our optima to real clinical protocols. We
recognize that the optimality of hypo or equi-fractionated treatment schemes
depends on the value of the tumour radiosensitivity ratio compared to the normal
tissue radiosensitivity. Fast growing, radioresistant tumours may require
particularly short optimal treatments.
PMID- 29346683
TI - Strigolactones: mediators of osmotic stress responses with a potential for
agrochemical manipulation of crop resilience.
AB - After quickly touching upon general aspects of strigolactone biology and
functions, including structure, synthesis, and perception, this review focuses on
the role and regulation of the strigolactone pathway during osmotic stress, in
light of the most recent research developments. We discuss available data on
organ-specific dynamics of strigolactone synthesis and interaction with abscisic
acid in the acclimatization response, with emphasis on the ecophysiological
implications of the effects on the stomatal closure process. We highlight the
importance of considering roots and shoots separately as well as combined versus
individual stress treatments; and of performing reciprocal grafting experiments
to work out organ contributions and long-distance signalling events and
components under more realistic conditions. Finally, we elaborate on the question
of if and how synthetic or natural strigolactones, alone or in combination with
crop management strategies such as grafting, hold potential to maximize crop
resilience to abiotic stresses.
PMID- 29346682
TI - Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of
Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human
Dipeptidyl Peptidase 4 Binding.
AB - Although bats are known to harbor Middle East Respiratory Syndrome coronavirus
(MERS-CoV)-related viruses, the role of bats in the evolutionary origin and
pathway remains obscure. We identified a novel MERS-CoV-related betacoronavirus,
Hp-BatCoV HKU25, from Chinese pipistrelle bats. Although it is closely related to
MERS-CoV in most genome regions, its spike protein occupies a phylogenetic
position between that of Ty-BatCoV HKU4 and Pi-BatCoV HKU5. Because Ty-BatCoV
HKU4 but not Pi-BatCoV HKU5 can use the MERS-CoV receptor human dipeptidyl
peptidase 4 (hDPP4) for cell entry, we tested the ability of Hp-BatCoV HKU25 to
bind and use hDPP4. The HKU25-receptor binding domain (RBD) can bind to hDPP4
protein and hDPP4-expressing cells, but it does so with lower efficiency than
that of MERS-RBD. Pseudovirus assays showed that HKU25-spike can use hDPP4 for
entry to hDPP4-expressing cells, although with lower efficiency than that of MERS
spike and HKU4-spike. Our findings support a bat origin of MERS-CoV and suggest
that bat CoV spike proteins may have evolved in a stepwise manner for binding to
hDPP4.
PMID- 29346684
TI - Comparing Cortical Trajectory Transforaminal Lumbar Interbody Fusions Against
Pedicle Trajectory Transforaminal Lumbar Interbody Fusions and Posterolateral
Fusions: A Retrospective Cohort Study of 90-day Outcomes.
AB - BACKGROUND: The cortical screw (CS) trajectory for pedicle screw placement is
believed to require a smaller incision and less tissue dissection resulting in
lower blood loss and faster healing; however, this has not yet been confirmed in
clinical studies. OBJECTIVE: To compare CS transforaminal lumbar interbody
fusions (TLIF), traditional pedicle screw (TPS) trajectory TLIFs, and
posterolateral fusion (PLF) without interbody for differences in operative
characteristics and complications. METHODS: We performed a retrospective cohort
study (CS, TPS, and PLF) looking at patients who underwent lumbar fusion with 1
or 2 levels. Extracted data included demographics, comorbidities, estimated blood
loss, transfusions, operative time, length of stay, discharge disposition (home
vs rehabilitation), and complications within the perioperative, 30- and 90-d
periods. RESULTS: A total of 118 patients (45 CS, 35 TPS, and 38 PLF) were
included with average age 62 and 90-d follow-up for 106 (90%) patients. CS had
less average blood loss (231 ml) than either TPS (424, P = .0023) or PLF (400, P
= .0070). CS had far fewer transfusions than either TPS or PLF (P < .0001). TPS
had longer average operating room (OR) time (262 min) than either CS (214, P =
.0075) or PLF (211, P = .0060). CS had the shortest length of postoperative stay
(4.3 days) which was significantly shorter than PLF (6.2, P = .0138) but not
different than TPS (4.8). There were no differences in discharge disposition,
complications, perioperative, 30-d, 90-d, durotomy, or wound healing issues.
CONCLUSION: The CS trajectory is associated with less blood loss, fewer
transfusions, reduced OR time, and shorter length of stay, with no difference in
complications.
PMID- 29346685
TI - Metabolic Flux Engineering of Cembratrien-ol Production in Both the Glandular
Trichome and Leaf Mesophyll in Nicotiana tabacum.
AB - Cembratrien-ol synthase (CBTS) catalyzes the first step in cembranoid
biosynthesis, producing cembratrien-ols in plant trichomes. In our previous
study, microarray transcriptomes between leaves with trichomes and leaves without
trichomes showed that an NtCBTS2 gene was expressed exclusively and abundantly in
trichomes. Here, two NtCBTS2 isogenes (NtCBTS2a and NtCBTS2b), derived from a
diploid genome donor, Nicotiana sylvestris, were identified from N. tabacum. Both
genes were expressed primarily in trichomes, with relatively decreased
transcription in flowers and stems, and faint expression in roots, and no
expression was detected in leaves lacking trichomes. To demonstrate the
feasibility of producing natural product cembratrien-ols in tobacco mesophylls,
the mesophylls of 35S:NtCBTS2b transgenic tobacco plants were used in the
analysis, suggesting that constitutive expression of NtCBTS2b led to the
cembratrien-ol production in mesophylls. Overexpression of NtCBTS2b using either
Cauliflower mosaic virus (CaMV) 35S or trichome-specific Cyt P450 oxygenase (CYP)
promoters greatly increased aphid resistance by promoting the accumulation of CBT
ols, increased the secretory cell growth in glandular trichomes and increased the
levels of various physiological measures, including sugar esters, gibberellins,
and cembranoid production. Meanwhile, specifically overexpressing NtCBTS2b in
glandular trichomes could most efficiently promote aphid resistance in tobacco
plants. Notably, our results indicate the feasibility of utilizing bio
engineering to produce large amounts of CBT-ols, and modify significantly the
composition of naturally produced CBT-ols and CBT-diols, thereby promoting aphid
resistance in plants.
PMID- 29346689
TI - Initial Development and Validation of a Family Medicine Attitudes Questionnaire.
AB - BACKGROUND AND OBJECTIVES: Although many curricular and policy interventions are
designed to influence students' attitudes toward family medicine, assessment of
these interventions is limited by lack of a comprehensive, validated measure of
students' attitudes. We sought to develop and validate a questionnaire that
effectively assesses medical student attitudes toward family medicine. METHODS: A
31-item questionnaire was assessed for internal, external, and content validity.
The questionnaire was offered to fourth-year students at two Midwestern medical
schools. Internal validity was assessed using data reduction and iterative factor
analyses. External validity was assessed by correlating scores with intention to
match in family medicine. Content validity was assessed by directly observing
students as they completed the questionnaire and qualitatively evaluating student
comments. RESULTS: Of 858 students invited, 426 (49.7%) provided usable
questionnaire data. After removal of questions with lower interitem correlations
and simplification of subscales, the modified questionnaire achieved acceptable
subscale internal consistency and a Cronbach alpha of 0.798. The overall
instrument summative score correlated with family medicine career choice
(P<0.001). Most subscales and individual items also correlated with family
medicine choice. Ten students were directly observed, using an iterative process,
and modifications were made based on student understanding. CONCLUSIONS:
Development of a validated questionnaire assessing medical student attitudes
toward family medicine is feasible. With further refinement, the Family Medicine
Attitudes Questionnaire may be useful in evaluating the impact of curricular
interventions on students' perceptions of family medicine, contributing to an
evidence-based approach to recruitment of students to the specialty.
PMID- 29346690
TI - Using Standardized Patient Assessments to Evaluate a Health Literacy Curriculum.
AB - BACKGROUND AND OBJECTIVES: Patients' health literacy is a growing concern as
patients are expected to perform more self-care. While many US schools implement
health literacy in their curricula, time spent on the topic ranges from 0 to 8
hours and is largely didactic. Evaluation of health literacy skills is not well
defined. The effectiveness of a health literacy curriculum for third-year medical
students was evaluated by two standardized patients assessments (SPAs). METHODS:
All third-year medical students complete a required 4-week clerkship in family
medicine. After participating in seminars on patient-centered communication,
health literacy, mindfulness, implicit bias, and chronic disease management,
students complete SPA-1. Students also work in two team-based teaching clinics
with chronic disease patients with limited health literacy and receive faculty
feedback. At week 4, students complete SPA-2. Six raters evaluated all video
recorded SPA performances using the Common Ground validated instrument and a
tailored health literacy skills checklist. RESULTS: Using SPAs and reliably
trained nonclinical raters is an effective method for training and evaluating
students about health literacy. Two classes (2013 and 2015) had significant
improvement in Common Ground core skills from SPA-1 to SPA-2. For all classes, a
small but significant increase in student use of health literacy checklist was
seen from SPA-1 to SPA-2. CONCLUSIONS: Didactic sessions prepare students to
demonstrate competence on Common Ground and health literacy skills. Improvements
in students' health literacy and communication skills are feasible in a 4-week
clerkship utilizing the curriculum and evaluation process described.
PMID- 29346691
TI - The Impact of Near-Peer Teaching on Medical Students' Transition to Clerkships.
AB - BACKGROUND AND OBJECTIVES: The transition to clerkships is one of the most
challenging times during medical school. To help students better cope, many
schools have established transition-to-clerkship curricula. Such curricula may
optimally prepare students through increasing their self-efficacy and response
efficacy. We hypothesized that a small-group, near-peer-led format would be
ideally suited to help students achieve these outcomes. METHODS: During process
improvement for a transition-to-clerkship curriculum, we conducted an informal
focus group and subsequent survey of postclerkship students to guide curricular
innovation, including incorporation of third- and fourth-year students as near
peer instructors in a seminar format. Seminars included three sequential small
group discussions focused on discrete topic areas and concluded with a large
group session highlighting salient discussion points. To evaluate the impact of
this educational strategy, near-peer learners were surveyed before and after the
seminars. RESULTS: Junior student participants reported feeling more prepared to
integrate into the health care team, develop a clerkship study plan, and access
applicable, valuable study materials, both immediately following the seminars and
6 months later, demonstrating increased self-efficacy. These students placed
equal or greater value on these topics as compared to students in previous year
groups, demonstrating similar response efficacy. CONCLUSIONS: This study
demonstrated an increase in student self-efficacy that persisted 6 months
postintervention, in addition to similar response efficacy. Future research could
be directed toward: (1) investigating whether improvements in self-efficacy among
students transitioning to clerkships are associated with improved clerkship
performance and (2) studying outcomes for near-peer teachers.
PMID- 29346692
TI - US Federal Policies Should Better Support the Primary Care Physician Workforce.
PMID- 29346693
TI - Clinical Experience in Medical School.
PMID- 29346694
TI - Vocation, Autonomy, Agency, and Meaning.
PMID- 29346695
TI - Symbols and Rituals of Healing.
PMID- 29346696
TI - An Unlikely Job Search Leads Home.
PMID- 29346697
TI - Surviving End-of-Life Care.
PMID- 29346698
TI - Procedural Knowledge and Skills of Residents Entering Canadian Family Medicine
Programs in Alberta.
AB - BACKGROUND AND OBJECTIVES: Incoming family medicine (FM) residents start
residency with different levels of procedural training. Understanding their
baseline skill level is necessary to plan the educational experiences and
teaching methods that will provide the desired knowledge, skills, and attitudes
related to performing medical procedures. METHODS: A survey of 69 procedures
based on the core list issued by the College of Family Physicians of Canada was
administered to incoming residents in Alberta (Calgary and Edmonton FM programs).
The survey intended to identify the levels of training and confidence acquired
for each listed procedure before residency, and plans to perform each of the
procedures in future independent practice. RESULTS: A total of 146 residents from
both programs responded to the survey (82% response rate). Of the 69 procedures
evaluated, 15 (21.7%) had been previously performed at least five times by 50% or
more residents. Only five procedures were rated by 80% or more of the residents
as being able to perform independently or to teach to others: simple suture,
infiltration of local anesthetic, intramuscular injection, cryotherapy of skin
lesions and Pap smear. More male residents than female residents felt confident
in performing 10 procedures, while female residents were more confident in
performing Pap smears. Rural residents felt more confident to perform 22
procedures than their urban colleagues. CONCLUSIONS: This information
demonstrates limited prior training in procedures among entering residents, and
provides guidance to FM programs to develop teaching interventions to achieve
competence in those procedural skills seen as necessary for family physicians.
PMID- 29346699
TI - Teaching Chronic Pain in the Family Medicine Residency.
AB - BACKGROUND AND OBJECTIVES: Chronic pain is a significant condition affecting many
Americans. Primary care physicians play an important role in chronic pain
management, but many residents and physicians feel poorly prepared to manage it.
METHODS: Data were collected as part of the 2016 Council of Academic Family
Medicine Educational Research Alliance (CERA) Program Director Survey, which was
sent electronically to 484 program directors in the United States. The authors
sought to determine whether residency directors' attitudes about treating chronic
pain were associated with the amount of time devoted to teaching family medicine
residents about chronic pain assessment, therapy (use of opioids, use adjuvant
pain medications, use of other nonopioids, use of nonpharmacological treatments),
and risk management (risk assessment, use of pain management contracts, informed
consent when prescribing opioids, and urine drug monitoring). Attitudes were
assessed by asking whether: (1) chronic pain is best managed by a primary care
physician (PCP); (2) prescribing opioid medications is time consuming; (3)
prescribing opioids is high-risk; (4) prescribing opioids contributes to opioid
misuse; and (4) effective nonopioid treatments exist. An additional question
assessed confidence in treating chronic pain. RESULTS: The response rate was 53%.
The average family medicine residency devotes about 33 hours to education about
pain management topics including 5.4 hours on chronic pain assessment, 16.2 hours
on therapy, and 11.4 hours on risk assessment. Residency directors' belief that
there are effective nonopioid treatments for chronic pain was the only attitude
item that was associated with teaching about chronic pain. CONCLUSIONS: Residency
directors' attitudes do not predict the time devoted to teaching chronic pain in
family medicine residencies.
PMID- 29346700
TI - Competence Revisited in a Rural Context.
AB - BACKGROUND AND OBJECTIVES: General competencies developed in undergraduate and
graduate medical education are sometimes promoted as applicable in any practice
context. However, rural practice presents challenges and opportunities that may
require unique training. The objectives of this national survey of both
undergraduate and graduate medical educators and practicing physicians were to
further develop a previously published list of competency domains for working in
rural communities and to assess their relative importance in education and
practice. METHODS: Using six rural competency domains first refined with a
national group at the Society of Teachers of Family Medicine Annual Meeting in
Baltimore in 2008, the authors employed a snowball strategy to survey medical
educators and physicians regarding the importance and relevance of this list and
to solicit additional domains and competencies. RESULTS: All six domains were
considered important, with average responses for each domain ranging from 4.16 to
4.78 on a 5-point Likert scale (1-not important; 5-extremely important). Unique
relevance to rural practice was more varied, with average responses for domains
ranging from 2.36 to 3.6 (1-not at all unique; 5-extremely unique). Analysis of
free text responses identified two important new domains-Comprehensiveness and
Agency/Courage-and provided clarification of some competencies within existing
domains. CONCLUSIONS: This study validates and further elaborates dimensions of
competence believed to be important in rural practice. The authors propose these
domains as a common language and framework for addressing the unique challenges
and opportunities that training and practicing in a rural setting present.
PMID- 29346701
TI - Identifying Prevalence and Characteristics of Behavioral Health Education in
Family Medicine Clerkships: A CERA Study.
AB - BACKGROUND AND OBJECTIVES: Many patients with behavioral health disorders do not
seek or receive adequate care for their conditions. Among those that do, most
will receive care in a primary care setting. To best meet this need, clinicians
will need to demonstrate proficiency of behavioral health skills and evidence
based practices. We sought to explore the degree to which these skills are being
taught in family medicine clerkships. METHODS: The Council of Academic Family
Medicine's (CAFM) Educational Research Alliance (CERA) 2016 survey of clerkship
directors (CDs) was sent to 141 CDs at US and Canadian medical schools with a
required family medicine run course. CDs were asked about the inclusion of
behavioral health topics, tools, and techniques in the clerkship, as well as
rating the importance of these items. RESULTS: Eighty-six percent of CDs
completed the survey. Mood disorders (81.4%) were most frequently taught,
followed by anxiety disorders (77.8%), substance use disorders (74.4%), and
impulse control disorders (39.1%). Screening tools and behavioral health
counseling skills were less commonly taught. CONCLUSIONS: Many behavioral health
topics are not taught universally to all family medicine clerkship students. Gaps
exist between what is included in current curriculum and what is recommended by
the National Clerkship Curriculum for family medicine. These gaps may represent
challenges for improving the care for patients with behavioral health disorders.
PMID- 29346702
TI - And an Equitable New Year.
PMID- 29346703
TI - Pursuing Personal Passion: Learner-Centered Research Mentoring.
AB - New researchers often face difficulty finding and focusing research questions. I
describe a new tool for research mentoring, the Pursuing Personal Passion (P3)
interview, and a systematic approach to help learners organize their curiosity
and develop researchable questions aligned with their personal and professional
priorities. The learner-centered P3 research interview parallels the patient
centered clinical interview. This paper reviews experience with 27 research
mentees over the years 2009 to 2016, using the P3 approach to identify their
initial research topics, classify their underlying passions and track the
evolution into their final research questions. These researchers usually
identified one of three personal passions that provided lenses to focus their
research: problem, person, or process. Initial research topics focused on:
problem (24%, 6), person (48%, 12) and process (28%, 7). Final research questions
evolved into: problem (20%, 5), person (32%, 8) and process (48%, 12).
Identification of the underlying passion can lead researchers who start with one
general topic to develop it into very different research questions. Using this P3
approach, mentors can help new researchers focus their interests into
researchable questions, successful studies, and organized programs of
scholarship.
PMID- 29346704
TI - Usefulness of live/real time three/four-dimensional transesophageal
echocardiography in the percutaneous closure of an iatrogenic aorto-right
ventricular fistula.
AB - The development of an aorto-right ventricular fistula is a rare complication of
cardiac surgery. The most common treatment is surgical closure of the fistula,
but percutaneous closure of the fistula has become an attractive alternative
option. We present a case of successful utilization of live/real time three/four
dimensional transoesophageal echocardiography (3/4DTEE) to select the correct
device size for percutaneous closure of an adult patient presenting with an aorto
right ventricular (AO-RV) fistula following aortic valve replacement. To the best
of our knowledge, this is the first case in which 3/4DTEE was used to select the
device size and guide percutaneous closure of an iatrogenic AO-RV fistula.
PMID- 29346705
TI - Effect of dys-1 mutation on gene expression profile in space-flown Caenorhabditis
elegans.
AB - INTRODUCTION: Dystrophin-like dys-1 gene expression increases in the body wall
muscles of Caenorhabditis elegans after spaceflight (SF). Here we used a dys
1(cx18) mutant to analyze the molecular adaptive responses of C. elegans to SF.
METHODS: DNA microarrays were performed to identify differentially expressed
genes between wild-type (WT) and dys-1 mutant worms after SF. We performed Gene
Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, predicted
human diseases, and screened out key genes for human muscle diseases with
NextBio. RESULTS: Gene expression was less affected by SF in the dys-1 mutant
than in the WT worms. The dys-1 mutation influenced neuromuscular gene expression
(neuropeptide genes, muscle-related genes, and dystrophin-related genes) under SF
conditions, among which 15 genes were specifically regulated by dys-1. NextBio
analysis predicted that cdka-1, lev-11, unc-27, and unc-94 genes might play
critical roles in muscle atrophy. DISCUSSION: dys-1 Potentially regulates the
neuromuscular system in space. Muscle Nerve, 2018.
PMID- 29346706
TI - Anti-3-hydroxy-3-methylglutaryl-coenzyme a reductase autoantibody-positive
necrotizing autoimmune myopathy with dermatomyositis-like eruption.
PMID- 29346707
TI - Tuning the High-Temperature Wetting Behavior of Metals toward Ultrafine
Nanoparticles.
AB - The interaction between metal nanoparticles (NPs) and their substrate plays a
critical role in determining the particle morphology, distribution, and
properties. The pronounced impact of a thin oxide coating on the dispersion of
metal NPs on a carbon substrate is presented. Al2 O3 -supported Pt NPs are
compared to the direct synthesis of Pt NPs on bare carbon surfaces. Pt NPs with
an average size of about 2 nm and a size distribution ranging between 0.5 nm and
4.0 nm are synthesized on the Al2 O3 coated carbon nanofiber, a significant
improvement compared to those directly synthesized on a bare carbon surface.
First-principles modeling verifies the stronger adsorption of Pt clusters on Al2
O3 than on carbon, which attributes the formation of ultrafine Pt NPs. This
strategy paves the way towards the rational design of NPs with enhanced
dispersion and controlled particle size, which are promising in energy storage
and electrocatalysis.
PMID- 29346708
TI - Role of comprehension on performance at higher levels of Bloom's taxonomy:
Findings from assessments of healthcare professional students.
AB - The first four levels of Bloom's taxonomy were used to create quiz questions
designed to assess student learning of the gross anatomy, histology, and
physiology of the gastrointestinal (GI) system. Information on GI histology and
physiology was presented to separate samples of medical, dental, and podiatry
students in computer based tutorials where the information from the two
disciplines was presented either separately or in an integrated fashion. All
students were taught GI gross anatomy prior to this study by course faculty as
part of the required curriculum of their respective program. Student responses to
the quiz questions were analyzed to assess both the validity of Bloom's
cumulative hierarchy and the effectiveness of an integrated curriculum. No
statistically significant differences were found between quiz scores from
students who received the integrated tutorial and from those who received the
separate tutorials. Multiple regression analyses provided partial support for a
cumulative hierarchy where scores on the lower levels of Bloom's taxonomy
predicted scores on higher levels. Notably, in the majority of regression
analyses, the comprehension score was the key foundational predictor for
application and analysis scores. This study supports the suggestion that
educators increase the number of comprehension level questions, even at the
expense of knowledge level questions, in course assessments both to evaluate
lower order cognitive skills and also as a predictor of success on questions
requiring application and analysis levels of the higher order cognitive skills of
Bloom's taxonomy. Anat Sci Educ 11: 433-444. (c) 2018 American Association of
Anatomists.
PMID- 29346709
TI - Rating the quality of a body of evidence on the effectiveness of health and
social interventions: A systematic review and mapping of evidence domains.
AB - INTRODUCTION: Rating the quality of a body of evidence is an increasingly common
component of research syntheses on intervention effectiveness. This study sought
to identify and examine existing systems for rating the quality of a body of
evidence on the effectiveness of health and social interventions. METHODS: We
used a multicomponent search strategy to search for full-length reports of
systems for rating the quality of a body of evidence on the effectiveness of
health and social interventions published in English from 1995 onward. Two
independent reviewers extracted data from each eligible system on the evidence
domains included, as well as the development and dissemination processes for each
system. RESULTS: Seventeen systems met our eligibility criteria. Across systems,
we identified 13 discrete evidence domains: study design, study execution,
consistency, measures of precision, directness, publication bias, magnitude of
effect, dose-response, plausible confounding, analogy, robustness, applicability,
and coherence. We found little reporting of rigorous procedures in the
development and dissemination of evidence rating systems. CONCLUSION: We
identified 17 systems for rating the quality of a body of evidence on
intervention effectiveness across health and social policy. Existing systems vary
greatly in the domains they include and how they operationalize domains, and most
have important limitations in their development and dissemination. The construct
of the quality of the body of evidence was defined in a few systems largely
extending the Grading of Recommendations Assessment, Development, and Evaluation
approach. Grading of Recommendations Assessment, Development, and Evaluation was
found to be unique in its comprehensive guidance, rigorous development, and
dissemination strategy.
PMID- 29346710
TI - An extensive caseous calcification of the mitral annulus complicated with severe
mitral regurgitation.
AB - Caseous calcification of the mitral annulus (CCMA) is considered a rare variant
of mitral annular calcification (MAC) due to caseous transformation of the inner
material and prevalence of CCMA, about 0.63% of all MAC cases and 0.06%-0.07% of
the population. The precise pathophysiology of CCMA is still unknown. It is a
chronic degenerative disorder common in the elderly, particularly in women.
Caseous calcification of the mitral annulus (CCMA) is a soft peri-annular
extensive calcification, resembling cardiac tumors, abscesses, vegetation, or
calcified thrombus, which is composed of an admixture of calcium, fatty acids,
and cholesterol with a toothpaste-like texture. In the characteristic appearance
on echocardiography, the calcification is a round, large, soft mass with a
central echo dense area, typically located at the basal area of the posterior
mitral valve. It usually carries a benign prognosis but rarely may be complicated
with mitral valve dysfunction (valve stenosis/mitral regurgitation) or systemic
embolization. The current data suggest conservative medical therapy and clinical
follow-up for management of CCMA unless there is a need of cardiac surgery for
severe mitral stenosis and/or regurgitation. We present a case, complicated with
severe mitral regurgitation, and need surgical resection of the CCMA because of
the CCMA-induced symptomatic severe mitral regurgitation despite optimal medical
therapy. Macroscopic and microscopic examination of caseous material also
demonstrated the characteristic appearance of CCMA.
PMID- 29346711
TI - Early assessment of post-surgical outcomes with pre-pectoral breast
reconstruction: A literature review and meta-analysis.
AB - BACKGROUND: Pre-pectoral breast reconstruction is an emerging surgical approach.
This study provides an early assessment of outcomes with the technique. METHODS:
A comprehensive literature review was performed through searches of PubMed(r)
/MEDLINE(r) to identify studies on pre-pectoral reconstruction. Patient
characteristics and outcomes were extracted from studies and pooled. Linear
relationships between complication rates and patient characteristics with pre
pectoral reconstruction were analyzed. A meta-analysis compared complication
rates between pre-pectoral and dual-plane reconstruction. RESULTS: Fourteen
studies (406 women/654 breasts) were included. The most common complications with
pre-pectoral reconstruction were flap necrosis (7.8%), seroma (6.7%), capsular
contracture (5.8%), and explantation (4.6%). No hyperanimation was reported.
Significant correlation between previous radiation and flap necrosis, post
operative chemotherapy and infection, hypertension and flap necrosis, diabetes
and dehiscence, and smoking and explantation were found. A meta-analysis of four
studies comparing pre-pectoral (135 women/219 breasts) and dual-plane (230/408)
reconstruction found no significant difference for likelihood of infection (odds
ratio, 0.46; 95% confidence interval, 0.16-1.30), explantation (0.83; 0.29-2.38),
necrosis (1.61; 0.77-3.36), seroma (1.88; 0.71-5.02), dehiscence (1.84; 0.68
4.95), or capsular contracture (0.14; 0.02-1.14). CONCLUSIONS: Complication rates
are comparable following pre-pectoral and dual-plane reconstruction, indicating
the pre-pectoral technique may be a feasible option for appropriate patients.
PMID- 29346712
TI - Synergetic Effects of Prenatal and Postnatal High Sucrose Intake on Glucose
Tolerance and Hepatic Insulin Resistance in Rat Offspring.
AB - SCOPE: High sucrose intake during pregnancy is linked to type 2 diabetes mellitus
and altered insulin resistance. METHODS AND RESULTS: This study attempts to
ascertain whether prenatal high sucrose intake (20% sucrose) alleviates the
detrimental effects of high postnatal sugar consumption in the offspring, and the
molecular mechanisms are investigated using a rat model. High prenatal sucrose
exposure increases the body weight of the offspring at 1-3 weeks of age. Exposure
to both prenatal and postnatal high sucrose increases glucose tolerance in the 4
month-old adult offspring compared with offspring receiving other treatments.
Postnatal high sucrose exposure suppresses food intake but increases the total
daily caloric and fluid intake. Both fasting blood glucose and plasma
triglyceride levels are increased, but the fasting insulin level is unaffected.
Prenatal high sucrose intake enlarges pancreatic islet area; however, prenatal
plus-postnatal high sucrose exposure induces smaller pancreatic islets. IRS
1(S612) protein phosphorylation is significantly increased, and the GSK-3beta
(S9) phosphorylation level is reduced. CONCLUSION: Both prenatal and prenatal
plus-postnatal high sucrose exposure substantially affect biological functions
related to insulin homeostasis. IRS-1(S612) protein phosphorylation appears to be
a part of the molecular mechanism underlying these effects. These results add to
the understanding of how high sucrose intake contributes to insulin resistance
and diabetes pathogenesis and how postnatal nutrition and lifestyle may mitigate
detrimental prenatal exposures.
PMID- 29346713
TI - Spark-generated microbubble cell sorter for microfluidic flow cytometry.
AB - High-speed and accurate cell sorting is of great significance for cell analysis
regarding both bioresearch and clinical application. Different from the jet-in
air sorting of commercial flow cytometers, sorting in fully enclosed and disposal
microfluidic chips can avoid aerosols and crosscontamination, thus contributing
to the improvement of biosafety and test accuracy. However, current microfluidic
sorters usually require complicated structures, or otherwise cannot attain high
throughput. In this article, a sorting mechanism for microfluidics is proposed
for the first time based on the jet flow induced by the spark-generated
cavitation microbubble that can be easily realized by a pair of electrodes. The
sorter was integrated into a microfluidic chip based on three-dimensional (3D)
hydrodynamic focusing and a binary optical element (BOE) for laser illumination.
Besides, several aspects of the sorting mechanism were studied to optimize the
device. It achieved a switching time of 250 MUs at the sample flow velocity of 5
m/s and performed the continuous operation at 200 Hz. Both the stability of
fluorescence signals and the viability of cells were basically maintained. To
conclude, this work explores a new on-chip sorting mechanism which possesses the
merits of simple structure, easy control, and fast switching. (c) 2018
International Society for Advancement of Cytometry.
PMID- 29346714
TI - "Vascular profiles" of regenerative and dysplastic nodules.
PMID- 29346715
TI - Duchenne muscular dystrophy caused by a novel deep intronic DMD mutation.
PMID- 29346716
TI - Neuropeptide AF Induces Piecemeal Degranulation in Murine Mucosal Mast Cells: A
New Mediator in Neuro-Immune Communication in the Intestinal Lamina Propria?
AB - Neuropeptides AF (NPAF), FF (NPFF) and SF (NPSF) are RFamide neuropeptides known
to be widely expressed in the mammalian central nervous system, where they
fulfill a wide range of functions with pain modulation being the most prominent
one. Recent evidence indicates that RFamides act as mediators in mast cell
sensory nerve communications related to allergic disease. Previous work by our
group has shown that the expression levels of some members of the Mas-related
gene receptor (Mrgpr) family in both enteric neurons and mucosal mast cells
change during intestinal inflammation. The Mrgpr subtypes C11 and A4 can be
activated by NPAF, while A1 and C11 are triggered by NPFF. The aim of the present
study was to investigate whether RFamides of the NPFF group are expressed in the
gastrointestinal tract and to identify possible targets and receptors that might
be involved in RFamide-associated mast cell modulation. To this end, the
expression and distribution patterns of NPFF/AF receptors and the NPFF precursor
protein were determined in bone marrow-derived mucosal mast cells (BMMCs) by
immunocytochemistry and (RT-) PCR. BMMCs were found to express MrgprA4 and A1,
and functional analysis of the effects of NPAF by means of a beta-hexosaminidase
assay, mMCP-1 ELISA, electron microscopy and live cell calcium imaging revealed a
piecemeal degranulation induced by NPAF. However, knock-out of MrgprA4 and A1 did
not reduce the effect of NPAF, indicating that the BMMC response to NPAF was
receptor independent. ProNPFF was expressed in neurons and BMMCs, suggesting that
both cell types are potential sources of NPAF in situ. Our results show that the
RFamide NPAF can be considered as a novel modulator of BMMC activity in the neuro
immune communication in the gastrointestinal tract, although the exact signaling
pathway remains to be elucidated. Anat Rec, 00:000-000, 2018. (c) 2018 Wiley
Periodicals, Inc. Anat Rec, 301:1103-1114, 2018. (c) 2018 Wiley Periodicals, Inc.
PMID- 29346718
TI - EDITORIAL.
PMID- 29346717
TI - Anterior cruciate ligament tear induces a sustained loss of muscle fiber force
production.
AB - INTRODUCTION: Patients with anterior cruciate ligament (ACL) tears have
persistent quadriceps strength deficits that are thought to be due to altered
neurophysiological function. Our goal was to determine the changes in muscle
fiber contractility independent of the ability of motor neurons to activate
fibers. METHODS: We obtained quadriceps biopsies of patients undergoing ACL
reconstruction, and additional biopsies 1, 2, and 6 months after surgery. Muscles
fiber contractility was assessed in vitro, along with whole muscle strength
testing. RESULTS: Compared with controls, patients had a 30% reduction in
normalized muscle fiber force at the time of surgery. One month later, the force
deficit was 41%, and at 6 months the deficit was 23%. Whole muscle strength
testing demonstrated similar trends. DISCUSSION: While neurophysiological
dysfunction contributes to whole muscle weakness, there is also a reduction in
the force generating capacity of individual muscle cells independent of alpha
motor neuron activation. Muscle Nerve, 2018.
PMID- 29346719
TI - A Tunable Molten-Salt Route for Scalable Synthesis of Ultrathin Amorphous Carbon
Nanosheets as High-Performance Anode Materials for Lithium-Ion Batteries.
AB - Amorphous carbon is regarded as a promising alternative to commercial graphite as
the lithium-ion battery anode due to its capability to reversibly store more
lithium ions. However, the structural disorder with a large number of defects can
lead to low electrical conductivity of the amorphous carbon, thus limiting its
application for high power output. Herein, ultrathin amorphous carbon nanosheets
were prepared from petroleum asphalt through tuning the carbonization temperature
in a molten-salt medium. The amorphous nanostructure with expanded carbon
interlayer spacing can provide substantial active sites for lithium storage,
while the two-dimensional (2D) morphology can facilitate fast electrical
conductivity. As a result, the electrodes deliver a high reversible capacity,
outstanding rate capability, and superior cycling performance (579 and 396 mAh g
1 at 2 and 5 A g-1 after 900 cycles). Furthermore, full cells consisting of the
carbon anodes coupled with LiMn2O4 cathodes exhibit high specific capacity (608
mAh g-1 at 50 mA g-1) and impressive cycling stability with slow capacity loss
(0.16% per cycle at 200 mA g-1). The present study not only paves the way for
industrial-scale synthesis of advanced carbon materials for lithium-ion batteries
but also deepens the fundamental understanding of the intrinsic mechanism of the
molten-salt method.
PMID- 29346720
TI - Nanoscale Control of Molecular Self-Assembly Induced by Plasmonic Hot-Electron
Dynamics.
AB - Self-assembly processes allow designing and creating complex nanostructures using
molecules as building blocks and surfaces as scaffolds. This autonomous driven
construction is possible due to a complex thermodynamic balance of molecule
surface interactions. As such, nanoscale guidance and control over this process
is hard to achieve. Here we use the highly localized light-to-chemical-energy
conversion of plasmonic materials to spatially cleave Au-S bonds on predetermined
locations within a single nanoparticle, enabling a high degree of control over
this archetypal system for molecular self-assembly. Our method offers nanoscale
precision and high-throughput light-induced tailoring of the surface chemistry of
individual and packed nanosized metallic structures by simply varying wavelength
and polarization of the incident light. Assisted by single-molecule super
resolution fluorescence microscopy, we image, quantify, and shed light onto the
plasmon-induced desorption mechanism. Our results point toward localized
distribution of hot electrons, contrary to uniformly distributed lattice heating,
as the mechanism inducing Au-S bond breaking. We demonstrate that plasmon-induced
photodesorption enables subdiffraction and even subparticle multiplexing.
Finally, we explore possible routes to further exploit these concepts for the
selective positioning of nanomaterials and the sorting and purification of
colloidal nanoparticles.
PMID- 29346721
TI - Emulsion Electrospinning of Polytetrafluoroethylene (PTFE) Nanofibrous Membranes
for High-Performance Triboelectric Nanogenerators.
AB - Electrospinning is a simple, versatile technique for fabricating fibrous
nanomaterials with the desirable features of extremely high porosities and large
surface areas. Using emulsion electrospinning, polytetrafluoroethylene/polyethene
oxide (PTFE/PEO) membranes were fabricated, followed by a sintering process to
obtain pure PTFE fibrous membranes, which were further utilized against a
polyamide 6 (PA6) membrane for vertical contact-mode triboelectric nanogenerators
(TENGs). Electrostatic force microscopy (EFM) measurements of the sintered
electrospun PTFE membranes revealed the presence of both positive and negative
surface charges owing to the transfer of positive charge from PEO which was
further corroborated by FTIR measurements. To enhance the ensuing triboelectric
surface charge, a facile negative charge-injection process was carried out onto
the electrospun (ES) PTFE subsequently. The fabricated TENG gave a stabilized
peak-to-peak open-circuit voltage (Voc) of up to ~900 V, a short-circuit current
density (Jsc) of ~20 mA m-2, and a corresponding charge density of ~149 MUC m-2,
which are ~12, 14, and 11 times higher than the corresponding values prior to the
ion-injection treatment. This increase in the surface charge density is caused by
the inversion of positive surface charges with the simultaneous increase in the
negative surface charge on the PTFE surface, which was confirmed by using EFM
measurements. The negative charge injection led to an enhanced power output
density of ~9 W m-2 with high stability as confirmed from the continuous
operation of the ion-injected PTFE/PA6 TENG for 30 000 operation cycles, without
any significant reduction in the output. The work thus introduces a relatively
simple, cost-effective, and environmentally friendly technique for fabricating
fibrous fluoropolymer polymer membranes with high thermal/chemical resistance in
TENG field and a direct ion-injection method which is able to dramatically
improve the surface negative charge density of the PTFE fibrous membranes.
PMID- 29346722
TI - Layer-by-Layer Epitaxial Growth of Defect-Engineered Strontium Cobaltites.
AB - Control over structure and composition of (ABO3) perovskite oxides offers
exciting opportunities since these materials possess unique, tunable properties.
Perovskite oxides with cobalt B-site cations are particularly promising, as the
range of the cation's stable oxidation states leads to many possible structural
frameworks. Here, we report growth of strontium cobalt oxide thin films by
molecular beam epitaxy, and conditions necessary to stabilize different defect
concentration phases. In situ X-ray scattering is used to monitor structural
evolution during growth, while in situ X-ray absorption near-edge spectroscopy is
used to probe oxidation state and measure changes to oxygen vacancy concentration
as a function of film thickness. Experimental results are compared to kinetically
limited thermodynamic predictions, in particular, solute trapping, with
semiquantitative agreement. Agreement between observations of dependence of
cobaltite phase on oxidation activity and deposition rate, and predictions
indicates that a combined experimental/theoretical approach is key to
understanding phase behavior in the strontium cobalt oxide system.
PMID- 29346723
TI - Shear-Induced Brittle Failure along Grain Boundaries in Boron Carbide.
AB - The role that grain boundaries (GBs) can play on mechanical properties has been
studied extensively for metals and alloys. However, for covalent solids such as
boron carbide (B4C), the role of GB on the inelastic response to applied stresses
is not well established. We consider here the unusual ceramic, boron carbide
(B4C), which is very hard and lightweight but exhibits brittle impact behavior.
We used quantum mechanics (QM) simulations to examine the mechanical response in
atomistic structures that model GBs in B4C under pure shear and also with biaxial
shear deformation that mimics indentation stress conditions. We carried out these
studies for two simple GB models including also the effect of adding Fe atoms
(possible sintering aid and/or impurity) to the GB. We found that the critical
shear stresses of these GB models are much lower than that for crystalline and
twinned B4C. The two GB models lead to different interfacial energies. The higher
interfacial energy at the GB only slightly decreases the critical shear stress
but dramatically increases the critical failure strain. Doping the GB with Fe
decreases the critical shear stress of at the boundary by 14% under pure shear
deformation. In all GBs studied here, failure arises from deconstructing the
icosahedra within the GB region under shear deformation. We find that Fe dopant
interacts with icosahedra at the GB to facilitate this deconstruction of
icosahedra. These results provide significant insight into designing
polycrystalline B4C with improved strength and ductility.
PMID- 29346724
TI - Structural and Biophysical Characterization of Human EXTL3: Domain Organization,
Glycosylation, and Solution Structure.
AB - Heparan sulfate proteoglycans are proteins substituted with one or more heparan
sulfate (HS) polysaccharides, found in abundance at cell surfaces. HS chains
influence the activity of many biologically important molecules involved in
cellular communication and signaling. The exostosin (EXT) proteins are
glycosyltransferases in the Golgi apparatus that assemble HS chains on HSPGs. The
EXTL3 enzyme mainly works as an initiator in HS biosynthesis. In this work, human
lumenal N-glycosylated EXTL3 (EXTL3DeltaN) was cloned, expressed in human
embryonic kidney cells, and purified. Various biophysical and biochemical
approaches were then employed to elucidate the N-glycosylation sites and the
function of their attached N-glycans. Furthermore, the stability and conformation
of the purified EXTL3DeltaN protein in solution have been analyzed. Our data show
that EXTL3DeltaN has N-glycans at least at two positions, Asn290 and Asn592,
which seem to be critical for proper protein folding and/or release. EXTL3DeltaN
is quite stable, as high temperature (~59 degrees C) was required for
denaturation. Deconvolution of the EXTL3DeltaN far-UV CD spectrum revealed a
substantial fraction of beta sheets (25%) with a minor proportion of alpha
helices (14%) in the secondary structure. Solution small-angle X-ray scattering
and dynamic light scattering revealed an extended structure suggestive of a
dimeric arrangement and consisting of two distinct regions, narrow and broad,
respectively. This is consistent with bioinformatics analyses suggesting a 3
domain structure with two glycosyltransferase domains and a coiled-coil domain.
PMID- 29346725
TI - Rapid Chemical Vapor Infiltration of Silicon Carbide Minicomposites at
Atmospheric Pressure.
AB - The chemical vapor infiltration technique is one of the most popular for the
fabrication of the matrix portion of a ceramic matrix composite. This work
focuses on tailoring an atmospheric pressure deposition of silicon carbide onto
carbon fiber tows using the methyltrichlorosilane (CH3SiCl3) and H2 deposition
system at atmospheric pressure to create minicomposites faster than low pressure
systems. Adjustment of the flow rate of H2 bubbled through CH3SiCl3 will improve
the uniformity of the deposition as well as infiltrate the substrate more
completely as the flow rate is decreased. Low pressure depositions conducted at
50 Torr deposit SiC at a rate of approximately 200 nm*h-1, while the atmospheric
pressure system presented has a deposition rate ranging from 750 nm*h-1 to 3.88
MUm*h-1. The minicomposites fabricated in this study had approximate total
porosities of 3 and 6% for 10 and 25 SCCM infiltrations, respectively.
PMID- 29346726
TI - The Effect of Dielectric Environment on Doping Efficiency in Colloidal PbSe
Nanostructures.
AB - Doping, as a central strategy to control free carrier type and concentration in
semiconductor materials, suffers from low efficiency at the nanoscale, especially
in systems having high permittivity (epsilon) and large Bohr radii, such as lead
chalcogenide nanocrystals (NCs) and nanowires (NWs). Here, we study dielectric
confinement effects on the doping efficiency of lead chalcogenides nanostructures
by integrating PbSe NWs in the platform of field effect transistors (FETs).
Elemental Pb or In or elemental Se is deposited by thermal evaporation to
remotely n- or p-dope the NWs. Polymeric and oxide materials of varying epsilon
are subsequently deposited to control the dielectric environment surrounding the
NWs. Analyzing the device characteristics, we extract the change of carrier
concentration introduced by tailoring the dielectric environment. The calculated
doping efficiency for n-type (Pb/In) and p-type (Se) dopants increases as the
epsilon of the surrounding medium increases. Using a high-epsilon material, such
as HfO2 for encapsulation, the doping efficiency can be enhanced by >10-fold. A
theoretical model is built to describe the doping efficiency in PbSe NWs embedded
in different dielectric environments, which agrees with our experimental data for
both NW array and single NW devices. As dielectric confinement affects all low
dimensional materials, engineering the dielectric environment is a promising
general approach to enhance doping concentrations, without introducing excess
impurities that may scatter carriers, and is suitable for various device
applications.
PMID- 29346727
TI - Bioinspired Pressure-Tolerant Asymmetric Slippery Surface for Continuous Self
Transport of Gas Bubbles in Aqueous Environment.
AB - Biosurfaces with geometry-gradient structures or special wettabilities
demonstrate intriguing performance in manipulating the behaviors of versatile
fluids. By mimicking natural species, that is, the cactus spine with a shape
gradient morphology and the Picher plant with a lubricated inner surface, we have
successfully prepared an asymmetric slippery surface by following the processes
of CO2-laser cutting, superhydrophobic modification, and the fluorinert infusion.
The asymmetric morphology will cause the deformation of gas bubbles and
subsequently engender an asymmetric driven force on them. Due to the infusion of
fluorinert, which has a low surface energy (~16 mN/m, 25 degrees C) and an easy
fluidic property (~0.75 cP, 25 degrees C), the slippery surface demonstrates
high adhesive force (~300 MUN) but low friction force on the gas bubbles. Under
the cooperation of the asymmetric morphology and fluorinert infused surface, the
fabricated asymmetric slippery surface is applicable to the directional and
continuous bubble delivery in an aqueous environment. More importantly, due to
the hard-compressed property of fluorinert, the asymmetric slippery surface is
facilitated with distinguished bubble transport capability even in a pressurized
environment (~0.65 MPa), showing its feasibility in practical industrial
production. In addition, asymmetric slippery surfaces with a snowflake-like
structure and a star-shaped structure were successfully fabricated for the real
world applications, both of which illustrated reliable performances in the
continuous generation, directional transportation, and efficient collection of
CO2 and H2 microbubbles.
PMID- 29346728
TI - Design and Assembly of Chiral Coordination Cages for Asymmetric Sequential
Reactions.
AB - Supramolecular nanoreactors featuring multiple catalytically active sites are of
great importance, especially for asymmetric catalysis, and are yet challenging to
construct. Here we report the design and assembly of five chiral single- and
mixed-linker tetrahedral coordination cages using six dicarboxylate ligands
derived-from enantiopure Mn(salen), Cr(salen) and/or Fe(salen) as linear linkers
and four Cp3Zr3 clusters as three-connected vertices. The formation of these
cages was confirmed by a variety of techniques including single-crystal and
powder X-ray diffraction, inductively coupled plasma optical emission
spectrometer, quadrupole-time-of-flight mass spectrometry and energy dispersive X
ray spectrometry. The cages feature a nanoscale hydrophobic cavity decorated with
the same or different catalytically active sites, and the mixed-linker cage
bearing Mn(salen) and Cr(salen) species is shown to be an efficient
supramolecular catalyst for sequential asymmetric alkene epoxidation/epoxide ring
opening reactions with up to 99.9% ee. The cage catalyst demonstrates improved
activity and enantioselectivity over the free catalysts owing to stabilization of
catalytically active metallosalen units and concentration of reactants within the
cavity. Manipulation of catalytic organic linkers in cages can control the
activities and selectivities, which may provide new opportunities for the design
and assembly of novel functional supramolecular architectures.
PMID- 29346729
TI - Electronic Interactions in Iminophosphorane Superbase Complexes with Carbon
Dioxide.
AB - Iminophosphoranes or phosphazenes are an important class of compounds with
increasing use in synthetic organic chemistry as neutral organic superbases
exhibiting low nucleophilicity. Their electronic structure and therefore their
properties strongly depend on substitution, but there have been very few
theoretical studies devoted to this topic, and more specifically to the formation
of electron donor-acceptor complexes of iminophosphoranes with electrophiles. In
this work, we have investigated the interaction with carbon dioxide at different
ab initio levels. Carbon dioxide usually behaves as a Lewis acid and the reaction
with iminiphosphoranes has been described as a nonconventional aza-Wittig process
leading to isocyanates. The reaction can be conducted in supercritical CO2
conditions (carbon dioxide acts as both solvent and reactant), which is a
promising strategy in the context of green chemistry. Our calculations have been
carried out at the CCSD(T)/aug-cc-pVTZ//MP2/aug-cc-pVTZ level for model systems
and at the M06-2X/6-611+G(d,p) level for a larger species used in experiments.
The electronic interactions and the interaction energies are analyzed and
discussed in detail using the natural bond orbital method. Proton affinities and
gas-phase basicities are provided as well.
PMID- 29346731
TI - Direct Polymerization of the Arsenic Drug PENAO to Obtain Nanoparticles with High
Thiol-Reactivity and Anti-Cancer Efficiency.
AB - PENAO (4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid), which is a
mitochondria inhibitor that reacts with adenine nucleotide translocator (ANT), is
currently being trialed in patients with solid tumors. To increase the stability
of the drug, the formation of nanoparticles has been proposed. Herein, the direct
synthesis of polymeric micelles based on the anticancer drug PENAO is presented.
PENAO is readily available for amidation reaction to form PENAO MA (4-(N-(S
penicillaminylacetyl) amino) phenylarsonous acid methacrylamide) which undergoes
RAFT (reversible addition-fragmentation chain transfer) polymerization with
poly(ethylene glycol methyl ether methacrylate) as comonomer and poly(methyl
methacrylate) (pMMA) as chain transfer agent, resulting in p(MMA)-b-p(PEG-co
PENAO) block copolymers with 3-15 wt % of PENAO MA. The different block
copolymers self-assembled into micelle structures, varying in size and stability
(Dh = 84-234 nm, cmc = 0.5-82 MUg mol-1) depending on the hydrophilic to
hydrophobic ratio of the polymer blocks and the amount of drug in the corona of
the particle. The more stable micelle structures were investigated toward 143B
human osteosarcoma cells, showing an enhanced cytotoxicity and cellular uptake
compared to the free drug PENAO (IC50 (PENAO) = 2.7 +/- 0.3 MUM; IC50 (micelle
M4) = 0.8 +/- 0.02 MUM). Furthermore, PENAOs arsonous acid residue remains active
when incorporated into a polymer matrix and conjugates to small mono and closely
spaced dithiols and is able to actively target the mitochondria, which is PENAO's
main target to introduce growth inhibition in cancer cells. As a result, no
cleavable linker between drug and polymer was necessary for the delivery of PENAO
to osteosarcoma cells. These findings provide a rationale for in vivo studies of
micelle M4 versus PENAO in an osteosarcoma animal model.
PMID- 29346732
TI - Microscopic Theory of Coupled Slow Activated Dynamics in Glass-Forming Binary
Mixtures.
AB - The Elastically Collective Nonlinear Langevin Equation theory for one-component
viscous liquids and suspensions is generalized to treat coupled slow activated
relaxation and diffusion in glass-forming binary sphere mixtures of any
composition, size ratio, and interparticle interactions. A trajectory-level
dynamical coupling parameter concept is introduced to construct two coupled
dynamic free energy functions for the smaller penetrant and larger matrix
particle. A two-step dynamical picture is proposed where the first-step process
involves matrix-facilitated penetrant hopping quantified in a self-consistent
manner based on a temporal coincidence condition. After penetrants dynamically
equilibrate, the effectively one-component matrix particle dynamics is controlled
by a new dynamic free energy (second-step process). Depending on the time scales
associated with the first- and second-step processes, as well as the extent of
matrix-correlated facilitation, distinct physical scenarios are predicted. The
theory is implemented for purely hard-core interactions, and addresses the glass
transition based on variable kinetic criteria, penetrant-matrix coupled activated
relaxation, self-diffusion of both species, dynamic fragility, and shear
elasticity. Testable predictions are made. Motivated by the analytic ultralocal
limit idea derived for pure hard sphere fluids, we identify structure
thermodynamics-dynamics relationships. As a case study for molecule-polymer
thermal mixtures, the chemically matched fully miscible polystyrene-toluene
system is quantitatively studied based on a predictive mapping scheme. The
resulting no-adjustable-parameter results for toluene diffusivity and the mixture
glass transition temperature are in good agreement with experiment. The theory
provides a foundation to treat diverse dynamical problems in glass-forming
mixtures, including suspensions of colloids and nanoparticles, polymer-molecule
liquids, and polymer nanocomposites.
PMID- 29346730
TI - Two-Dimensional Spectroscopy Is Being Used to Address Core Scientific Questions
in Biology and Materials Science.
AB - Two-dimensional spectroscopy is a powerful tool for extracting structural and
dynamic information from a wide range of chemical systems. We provide a brief
overview of the ways in which two-dimensional visible and infrared spectroscopies
are being applied to elucidate fundamental details of important processes in
biological and materials science. The topics covered include amyloid proteins,
photosynthetic complexes, ion channels, photovoltaics, batteries, as well as a
variety of promising new methods in two-dimensional spectroscopy.
PMID- 29346733
TI - Synthesis and Structure-Activity Relationship (SAR) Studies of Novel
Pyrazolopyridine Derivatives as Inhibitors of Enterovirus Replication.
AB - A series of novel pyrazolopyridine compounds have been designed and prepared by a
general synthetic route. Their activities against the replication of poliovirus
1, EV-A71, and CV-B3 enteroviruses were evaluated. The comprehensive
understanding of the structure-activity relationship was obtained by utilizing
the variation of four positions, namely, N1, C6, C4, and linker unit. From the
screened analogues, the inhibitors with the highest selectivity indices at 50%
inhibition of viral replication (SI50) were those with isopropyl at the N1
position and thiophenyl-2-yl unit at C6 position. Furthermore, the C4 position
offered the greatest potential for improvement because many different N-aryl
groups had better antiviral activities and compatibilities than the lead compound
JX001. For example, JX040 with a 2-pyridyl group was the analogue with the most
potent activity against non-polio enteroviruses, and JX025, possessing a 3
sulfamoylphenyl moiety, had the best activity against polioviruses. In addition,
analogue JX037, possessing a novel pyrazolopyridine heterocycle, was also shown
to have good antienteroviral activity, which further enlarges the compound space
for antienteroviral drug design.
PMID- 29346734
TI - Fluctuation Effects on the Brush Structure of Mixed Brush Nanoparticles in
Solution.
AB - A potentially attractive way to control nanoparticle assembly is to graft one or
more polymers on the nanoparticle, to control the nanoparticle-nanoparticle
interactions. When two immiscible polymers are grafted on the nanoparticle, they
can microphase separate to form domains at the nanoparticle surface. Here, we
computationally investigate the phase behavior of such binary mixed brush
nanoparticles in solution, across a large and experimentally relevant parameter
space. Specifically, we calculate the mean-field phase diagram, assuming uniform
grafting of the two polymers, as a function of the nanoparticle size relative to
the length of the grafted chains, the grafting density, the enthalpic repulsion
between the grafted chains, and the solvent quality. We find a variety of phases
including a Janus phase and phases with varying numbers of striped domains. Using
a nonuniform, random distribution of grafting sites on the nanoparticle instead
of the uniform distribution leads to the development of defects in the mixed
brush structures. Introducing fluctuations as well leads to increasingly
defective structures for the striped phases. However, we find that the simple
Janus phase is preserved in all calculations, even with the introduction of
nonuniform grafting and fluctuations. We conclude that the formation of the Janus
phase is more realistic experimentally than is the formation of defect-free
multivalent mixed brush nanoparticles.
PMID- 29346735
TI - Mechanisms of Modulation of Calcium Phosphate Pathological Mineralization by
Mobile and Immobile Small-Molecule Inhibitors.
AB - Potential pathways for inhibiting crystal growth are via either disrupting local
microenvironments surrounding crystal-solution interfaces or physically blocking
solute molecule attachment. However, the actual mode of inhibition may be more
complicated due to the characteristic time scale for the inhibitor adsorption and
relaxation to a well-bound state at crystal surfaces. Here we demonstrate the
role of citrate (CA) and hydroxycitrate (HCA) in brushite (DCPD, CaHPO4.2H2O)
crystallization over a broad range of both inhibitor concentrations and
supersaturations by in situ atomic force microscopy (AFM). We observed that both
inhibitors exhibit two distinct actions: control of surface crystallization by
the decrease of step density at high supersaturations and the decrease of the
[100]Cc step velocity at high inhibitor concentration and low supersaturation.
The switching of the two distinct modes depends on the terrace lifetime, and the
slow kinetics along the [100]Cc step direction provides specific sites for the
newly formed dislocations. Molecular modeling shows the strong HCA-crystal
interaction by molecular recognition, explaining the AFM observations for the
formation of new steps and surface dissolution along the [101]Cc direction due to
the introduction of strong localized strain in the crystal lattice. These direct
observations highlight the importance of the inhibitor coverage on mineral
surfaces, as well as the solution supersaturation in predicting the inhibition
efficacy, and reveal an improved understanding of inhibition of calcium phosphate
biomineralization, with clinical implications for the full therapeutic potential
of small-molecule inhibitors for kidney stone disease.
PMID- 29346736
TI - Light-Activatable Red Blood Cell Membrane-Camouflaged Dimeric Prodrug
Nanoparticles for Synergistic Photodynamic/Chemotherapy.
AB - Biomimetic approach offers numerous opportunities to design therapeutic platforms
with enhanced antitumor performance and biocompatibility. Herein we report red
blood cell membrane-camouflaged nanoparticles (RBC(M(TPC-PTX))) for synergistic
chemo- and photodynamic therapy (PDT). Specifically, the inner core is mainly
constructed by reactive oxygen species (ROS)-responsive PTX dimer (PTX2-TK) and
photosensitizer 5,10,15,20-tetraphenylchlorin (TPC). In vitro experiments show
that the prepared RBC(M(TPC-PTX)) is readily taken up into endosomes. Under
appropriate light irradiation, the TPC can generate ROS, not only for PDT but
also for triggering PTX2-TK cleavage and on-demand PTX release for chemotherapy.
In vivo results show that the coating of RBC membrane prolongs blood circulation
and improves tumor accumulation. The combination of chemo- and photodynamic
therapy enhances anticancer therapeutic activity, and light-triggered drug
release reduces systematic toxicity. All these characteristics render the
described technology extremely promising for cancer treatment.
PMID- 29346737
TI - Quantitative and Qualitative Assessment of the Relative Arterial Contributions to
the Calcaneus.
AB - BACKGROUND: The purpose of this study was to quantitatively and qualitatively
assess relative arterial contributions to the calcaneus. METHOD: Fourteen
cadaveric ankle pairs were used. In each specimen, the posterior tibial artery,
peroneal artery, and anterior tibial artery were cannulated and used for contrast
enhanced magnetic resonance imaging (MRI) and computed tomography (CT).
Quantitative MRI analysis of the pre- and postcontrast MRI scans facilitated
assessment of relative arterial contributions. In addition, postcontrast MRIs
were used to measure all perfused arterial entry points and scaled to a 3
dimensional calcaneus model. Contrast-enhanced CT imaging was assessed to further
delineate the extraosseous arterial course. Two pairs underwent infusion of
diluted BaSO4 through a constant-pressure pump using extended infusion duration.
RESULTS: Quantitative MRI findings indicated the peroneal artery provided 52.6%
of the calcaneal arterial supply, 31.6% from the posterior tibial artery, and
15.8% from the anterior tibial artery. The cortical entry points were found in
fairly consistent patterns along calcaneal cortical surfaces. All specimens
demonstrated intraosseous anastomoses between lateral and medial entry points at
common locations. CONCLUSIONS: The peroneal artery was found to provide the
largest calcaneal arterial contribution, followed by the posterior tibial artery
and anterior tibial artery. A rich anastomotic arterial network was found
supplying the calcaneus. CLINICAL RELEVANCE: This study provides quantitative and
qualitative findings of the relative arterial contribution of the calcaneus. This
knowledge can help expand our understanding of calcaneal vascularization,
demonstrate the vascular impact of calcaneal fracture and surgery, and facilitate
future research on the arterial anatomy of the calcaneal soft tissue envelope.
PMID- 29346738
TI - First Record of Leucocytozoon (Haemosporida: Leucocytozoidae) in Amazonia:
Evidence for Rarity in Neotropical Lowlands or Lack of Sampling for This Parasite
Genus?
AB - Birds harbor an astonishing diversity of haemosporidian parasites belonging to
the genera Haemoproteus, Leucocytozoon, and Plasmodium. Currently there are more
than 250 morphologically described avian haemosporidian species and 2,828 unique
lineages found in virtually all avian clades and zoogeographic regions, except
for Antarctica. Our report is based on PCR and microscopic screening of 1,302
individual avian samples from Brazil to detect the underrepresented genus
Leucocytozoon. This survey primarily focuses on passerine birds collected from
Amazonia, the Atlantic Rain Forest, and Pantanal. We also summarize studies
conducted in Brazil that report haemosporidian prevalence using both microscopy
and molecular tools and present for the first time a record of Leucocytozoon
infecting an avian host population in Amazonia. Based on our findings, we suggest
that high average temperatures may be constraining both the distribution and
diversity of Leucocytozoon in lowland tropical South America.
PMID- 29346739
TI - The Role of the Diabetes Educator in Diabetes Formulary and Medical Device
Decisions.
AB - It is the position of the American Association of Diabetes Educators that
diabetes educators should be included as expert consultants for formulary
decisions regarding diabetes medications and medical devices.
PMID- 29346740
TI - Role of the Diabetes Educator in Inpatient Diabetes Management.
AB - It is the position of American Association of Diabetes Educators (AADE) that all
inpatient interdisciplinary teams include a diabetes educator to lead or support
improvement efforts that affect patients hospitalized with diabetes or
hyperglycemia. This not only encompasses patient and family education but
education of interdisciplinary team members and achievement of diabetes-related
organizational quality metrics and performance outcomes.
PMID- 29346742
TI - Management of Children With Diabetes in the School Setting.
AB - Diabetes educators are well positioned to help optimize care of the student with
diabetes within the school setting.
PMID- 29346743
TI - Publishing AADE's Position Statements.
PMID- 29346745
TI - The THIK and Thin of Microglia Dynamics.
AB - Madry et al. (2018) show that the two-pore potassium channel THIK-1 is tonically
active in microglia and promotes microglial ramification and surveillance of the
brain parenchyma. Interestingly, THIK-1 is not essential to damage-induced
outgrowth of microglial processes but is critical to microglial IL-1beta release.
PMID- 29346744
TI - 2017 National Standards for Diabetes Self-Management Education and Support.
AB - Purpose The purpose of this study is to review the literature for Diabetes Self
Management Education and Support (DSMES) to ensure the National Standards for
DSMES (Standards) align with current evidence-based practices and utilization
trends. Methods The 10 Standards were divided among 20 interdisciplinary
workgroup members. Members searched the current research for diabetes education
and support, behavioral health, clinical, health care environment, technical,
reimbursement, and business practice for the strongest evidence that guided the
Standards revision. Results Diabetes Self-Management Education and Support
facilitates the knowledge, skills, and ability necessary for diabetes self-care
as well as activities that assist a person in implementing and sustaining the
behaviors needed to manage their condition on an ongoing basis. The evidence
indicates that health care providers and people affected by diabetes are
embracing technology, and this is having a positive impact of DSMES access,
utilization, and outcomes. Conclusion Quality DSMES continues to be a critical
element of care for all people with diabetes. The DSMES services must be
individualized and guided by the concerns, preferences, and needs of the person
affected by diabetes. Even with the abundance of evidence supporting the benefits
of DSMES, it continues to be underutilized, but as with other health care
services, technology is changing the way DSMES is delivered and utilized with
positive outcomes.
PMID- 29346746
TI - Shh-ushing Midline Crossing through Remote Protein Transport.
AB - Shh contributes to neural circuit formation with different mechanisms. In this
issue, Peng and colleagues (2018) identify a novel trans-axonal mechanism by
which Shh derived from contralateral projecting retinal ganglion cells prevents
midline crossing of Boc-expressing ipsilateral axons at the optic chiasm.
PMID- 29346747
TI - Sensorimotor Integration for Decision Making: How the Worm Steers.
AB - Animals' movements actively shape their perception and subsequent decision
making. In this issue of Neuron, Liu et al. (2018) show how C. elegans nematodes
steer toward an odorant: a dedicated interneuron class integrates oscillatory
olfactory signals, generated by head swings, with corollary discharge motor
signals.
PMID- 29346748
TI - Spiraling Connectivity of NAc-VTA Circuitry.
AB - How do nucleus accumbens (NAc) subdivisions shape information flow into distinct
ventral tegmental area (VTA) subcircuits? Yang et al. (2018) provide insightful
answers to this question by expanding our knowledge about the circuit
architecture and function of reciprocal connectivity between NAc and VTA.
PMID- 29346749
TI - Statistical Challenges in "Big Data" Human Neuroimaging.
AB - Smith and Nichols discuss "big data" human neuroimaging studies, with very large
subject numbers and amounts of data. These studies provide great opportunities
for making new discoveries about the brain but raise many new analytical
challenges and interpretational risks.
PMID- 29346750
TI - From Healthcare to Warfare and Reverse: How Should We Regulate Dual-Use
Neurotechnology?
AB - Recent advances in military-funded neurotechnology and novel opportunities for
misusing neurodevices show that the problem of dual use is inherent to
neuroscience. This paper discusses how the neuroscience community should respond
to these dilemmas and delineates a neuroscience-specific biosecurity framework.
This neurosecurity framework involves calibrated regulation, (neuro)ethical
guidelines, and awareness-raising activities within the scientific community.
PMID- 29346751
TI - The Brain Compass: A Perspective on How Self-Motion Updates the Head Direction
Cell Attractor.
AB - Head direction cells form an internal compass signaling head azimuth orientation
even without visual landmarks. This property is generated by a neuronal ring
attractor that is updated using rotation velocity cues. The properties and origin
of this velocity drive remain, however, unknown. We propose a quantitative
framework whereby this drive represents a multisensory self-motion estimate
computed through an internal model that uses sensory prediction errors of
vestibular, visual, and somatosensory cues to improve on-line motor drive. We
show how restraint-dependent strength of recurrent connections within the
attractor can explain differences in head direction cell firing between free
foraging and restrained passive rotation. We also summarize recent findings on
how gravity influences azimuth coding, indicating that the velocity drive is not
purely egocentric. Finally, we show that the internal compass may be three
dimensional and hypothesize that the additional vertical degrees of freedom use
global allocentric gravity cues.
PMID- 29346753
TI - Sonic Hedgehog Is a Remotely Produced Cue that Controls Axon Guidance Trans
axonally at a Midline Choice Point.
AB - At the optic chiasm choice point, ipsilateral retinal ganglion cells (RGCs) are
repelled away from the midline by guidance cues, including Ephrin-B2 and Sonic
Hedgehog (Shh). Although guidance cues are normally produced by cells residing at
the choice point, the mRNA for Shh is not found at the optic chiasm. Here we show
that Shh protein is instead produced by contralateral RGCs at the retina,
transported anterogradely along the axon, and accumulates at the optic chiasm to
repel ipsilateral RGCs. In vitro, contralateral RGC axons, which secrete Shh,
repel ipsilateral RGCs in a Boc- and Smo-dependent manner. Finally, knockdown of
Shh in the contralateral retina causes a decrease in the proportion of
ipsilateral RGCs in a non-cell-autonomous manner. These findings reveal a role
for axon-axon interactions in ipsilateral RGC guidance, and they establish that
remotely produced cues can act at axon guidance midline choice points.
PMID- 29346752
TI - Epitranscriptomic m6A Regulation of Axon Regeneration in the Adult Mammalian
Nervous System.
AB - N6-methyladenosine (m6A) affects multiple aspects of mRNA metabolism and
regulates developmental transitions by promoting mRNA decay. Little is known
about the role of m6A in the adult mammalian nervous system. Here we report that
sciatic nerve lesion elevates levels of m6A-tagged transcripts encoding many
regeneration-associated genes and protein translation machinery components in the
adult mouse dorsal root ganglion (DRG). Single-base resolution m6A-CLIP mapping
further reveals a dynamic m6A landscape in the adult DRG upon injury. Loss of
either m6A methyltransferase complex component Mettl14 or m6A-binding protein
Ythdf1 globally attenuates injury-induced protein translation in adult DRGs and
reduces functional axon regeneration in the peripheral nervous system in vivo.
Furthermore, Pten deletion-induced axon regeneration of retinal ganglion neurons
in the adult central nervous system is attenuated upon Mettl14 knockdown. Our
study reveals a critical epitranscriptomic mechanism in promoting injury-induced
protein synthesis and axon regeneration in the adult mammalian nervous system.
PMID- 29346755
TI - Connecting Neural Codes with Behavior in the Auditory System of Drosophila.
PMID- 29346754
TI - Input-Specific NMDAR-Dependent Potentiation of Dendritic GABAergic Inhibition.
AB - Preservation of a balance between synaptic excitation and inhibition is critical
for normal brain function. A number of homeostatic cellular mechanisms have been
suggested to play a role in maintaining this balance, including long-term
plasticity of GABAergic inhibitory synapses. Many previous studies have
demonstrated a coupling of postsynaptic spiking with modification of perisomatic
inhibition. Here, we demonstrate that activation of NMDA-type glutamate receptors
leads to input-specific long-term potentiation of dendritic inhibition mediated
by somatostatin-expressing interneurons. This form of plasticity is expressed
postsynaptically and requires both CaMKIIalpha and the beta2 subunit of the GABA
A receptor. Importantly, this process may function to preserve dendritic
inhibition, as genetic deletion of NMDAR signaling results in a selective
weakening of dendritic inhibition. Overall, our results reveal a new mechanism
for linking excitatory and inhibitory input in neuronal dendrites and provide
novel insight into the homeostatic regulation of synaptic transmission in
cortical circuits.
PMID- 29346756
TI - Exploration Disrupts Choice-Predictive Signals and Alters Dynamics in Prefrontal
Cortex.
PMID- 29346757
TI - p53 Suppresses Metabolic Stress-Induced Ferroptosis in Cancer Cells.
AB - How cancer cells respond to nutrient deprivation remains poorly understood. In
certain cancer cells, deprivation of cystine induces a non-apoptotic, iron
dependent form of cell death termed ferroptosis. Recent evidence suggests that
ferroptosis sensitivity may be modulated by the stress-responsive transcription
factor and canonical tumor suppressor protein p53. Using CRISPR/Cas9 genome
editing, small-molecule probes, and high-resolution, time-lapse imaging, we find
that stabilization of wild-type p53 delays the onset of ferroptosis in response
to cystine deprivation. This delay requires the p53 transcriptional target CDKN1A
(encoding p21) and is associated with both slower depletion of intracellular
glutathione and a reduced accumulation of toxic lipid-reactive oxygen species
(ROS). Thus, the p53-p21 axis may help cancer cells cope with metabolic stress
induced by cystine deprivation by delaying the onset of non-apoptotic cell death.
PMID- 29346758
TI - Size-Dependent Axonal Bouton Dynamics following Visual Deprivation In Vivo.
AB - Persistent synapses are thought to underpin the storage of sensory experience,
yet little is known about their structural plasticity in vivo. We investigated
how persistent presynaptic structures respond to the loss of primary sensory
input. Using in vivo two-photon (2P) imaging, we measured fluctuations in the
size of excitatory axonal boutons in L2/3 of adult mouse visual cortex after
monocular enucleation. The average size of boutons did not change after
deprivation, but the range of bouton sizes was reduced. Large boutons decreased,
and small boutons increased. Reduced bouton variance was accompanied by a reduced
range of correlated calcium-mediated neural activity in L2/3 of awake animals.
Network simulations predicted that size-dependent plasticity may promote
conditions of greater bidirectional plasticity. These predictions were supported
by electrophysiological measures of short- and long-term plasticity. We propose
size-dependent dynamics facilitate cortical reorganization by maximizing the
potential for bidirectional plasticity.
PMID- 29346760
TI - Single-Cell Transcriptional Profiling Reveals Cellular Diversity and
Intercommunication in the Mouse Heart.
AB - Characterization of the cardiac cellulome, the network of cells that form the
heart, is essential for understanding cardiac development and normal organ
function and for formulating precise therapeutic strategies to combat heart
disease. Recent studies have reshaped our understanding of cardiac cellular
composition and highlighted important functional roles for non-myocyte cell
types. In this study, we characterized single-cell transcriptional profiles of
the murine non-myocyte cardiac cellular landscape using single-cell RNA
sequencing (scRNA-seq). Detailed molecular analyses revealed the diversity of the
cardiac cellulome and facilitated the development of techniques to isolate
understudied cardiac cell populations, such as mural cells and glia. Our analyses
also revealed extensive networks of intercellular communication and suggested
prevalent sexual dimorphism in gene expression in the heart. This study offers
insights into the structure and function of the mammalian cardiac cellulome and
provides an important resource that will stimulate studies in cardiac cell
biology.
PMID- 29346759
TI - NF-kappaB-Chromatin Interactions Drive Diverse Phenotypes by Modulating
Transcriptional Noise.
AB - Noisy gene expression generates diverse phenotypes, but little is known about
mechanisms that modulate noise. Combining experiments and modeling, we studied
how tumor necrosis factor (TNF) initiates noisy expression of latent HIV via the
transcription factor nuclear factor kappaB (NF-kappaB) and how the HIV genomic
integration site modulates noise to generate divergent (low-versus-high)
phenotypes of viral activation. We show that TNF-induced transcriptional noise
varies more than mean transcript number and that amplification of this noise
explains low-versus-high viral activation. For a given integration site, live
cell imaging shows that NF-kappaB activation correlates with viral activation,
but across integration sites, NF-kappaB activation cannot account for differences
in transcriptional noise and phenotypes. Instead, differences in transcriptional
noise are associated with differences in chromatin state and RNA polymerase II
regulation. We conclude that, whereas NF-kappaB regulates transcript abundance in
each cell, the chromatin environment modulates noise in the population to support
diverse HIV activation in response to TNF.
PMID- 29346761
TI - INO80 Chromatin Remodeling Coordinates Metabolic Homeostasis with Cell Division.
AB - Adaptive survival requires the coordination of nutrient availability with
expenditure of cellular resources. For example, in nutrient-limited environments,
50% of all S. cerevisiae genes synchronize and exhibit periodic bursts of
expression in coordination with respiration and cell division in the yeast
metabolic cycle (YMC). Despite the importance of metabolic and proliferative
synchrony, the majority of YMC regulators are currently unknown. Here, we
demonstrate that the INO80 chromatin-remodeling complex is required to coordinate
respiration and cell division with periodic gene expression. Specifically, INO80
mutants have severe defects in oxygen consumption and promiscuous cell division
that is no longer coupled with metabolic status. In mutant cells, chromatin
accessibility of periodic genes, including TORC1-responsive genes, is relatively
static, concomitant with severely attenuated gene expression. Collectively, these
results reveal that the INO80 complex mediates metabolic signaling to chromatin
to restrict proliferation to metabolically optimal states.
PMID- 29346762
TI - Transcriptome and DNA Methylome Analysis in a Mouse Model of Diet-Induced Obesity
Predicts Increased Risk of Colorectal Cancer.
AB - Colorectal cancer (CRC) tends to occur at older age; however, CRC incidence rates
have been rising sharply among young age groups. The increasing prevalence of
obesity is recognized as a major risk, yet the mechanistic underpinnings remain
poorly understood. Using a diet-induced obesity mouse model, we identified
obesity-associated molecular changes in the colonic epithelium of young and aged
mice, and we further investigated whether the changes were reversed after weight
loss. Transcriptome analysis indicated that obesity-related colonic cellular
metabolic switch favoring long-chain fatty acid oxidation happened in young mice,
while obesity-associated downregulation of negative feedback regulators of pro
proliferative signaling pathways occurred in older mice. Strikingly, colonic DNA
methylome was pre-programmed by obesity at young age, priming for a tumor-prone
gene signature after aging. Furthermore, obesity-related changes were
substantially preserved after short-term weight loss, but they were largely
reversed after long-term weight loss. We provided mechanistic insights into
increased CRC risk in obesity.
PMID- 29346763
TI - Derepression of the Iroquois Homeodomain Transcription Factor Gene IRX3 Confers
Differentiation Block in Acute Leukemia.
AB - The Iroquois homeodomain transcription factor gene IRX3 is expressed in the
developing nervous system, limb buds, and heart, and transcript levels specify
obesity risk in humans. We now report a functional role for IRX3 in human acute
leukemia. Although transcript levels are very low in normal human bone marrow
cells, high IRX3 expression is found in ~30% of patients with acute myeloid
leukemia (AML), ~50% with T-acute lymphoblastic leukemia, and ~20% with B-acute
lymphoblastic leukemia, frequently in association with high-level HOXA gene
expression. Expression of IRX3 alone was sufficient to immortalize hematopoietic
stem and progenitor cells (HSPCs) in myeloid culture and induce lymphoid
leukemias in vivo. IRX3 knockdown induced terminal differentiation of AML cells.
Combined IRX3 and Hoxa9 expression in murine HSPCs impeded normal T-progenitor
differentiation in lymphoid culture and substantially enhanced the morphologic
and phenotypic differentiation block of AML in myeloid leukemia transplantation
experiments through suppression of a terminal myelomonocytic program. Likewise,
in cases of primary human AML, high IRX3 expression is strongly associated with
reduced myelomonocytic differentiation. Thus, tissue-inappropriate derepression
of IRX3 contributes significantly to the block in differentiation, which is the
pathognomonic feature of human acute leukemias.
PMID- 29346764
TI - SGK1 Governs the Reciprocal Development of Th17 and Regulatory T Cells.
AB - A balance between Th17 and regulatory T (Treg) cells is critical for immune
homeostasis and tolerance. Our previous work has shown Serum- and glucocorticoid
induced kinase 1 (SGK1) is critical for the development and function of Th17
cells. Here, we show that SGK1 restrains the function of Treg cells and
reciprocally regulates development of Th17/Treg balance. SGK1 deficiency leads to
protection against autoimmunity and enhances self-tolerance by promoting Treg
cell development and disarming Th17 cells. Treg cell-specific deletion of SGK1
results in enhanced Treg cell-suppressive function through preventing Foxo1 out
of the nucleus, thereby promoting Foxp3 expression by binding to Foxp3 CNS1
region. Furthermore, our data suggest that SGK1 also plays a critical role in IL
23R-mediated inhibition of Treg and development of Th17 cells. Therefore, we
demonstrate that SGK1 functions as a pivotal node in regulating the reciprocal
development of pro-inflammatory Th17 and Foxp3+ Treg cells during autoimmune
tissue inflammation.
PMID- 29346765
TI - Characterization of Endothelial Cells Associated with Hematopoietic Niche
Formation in Humans Identifies IL-33 As an Anabolic Factor.
AB - Bone marrow formation requires an orchestrated interplay between osteogenesis,
angiogenesis, and hematopoiesis that is thought to be mediated by endothelial
cells. The nature of the endothelial cells and the molecular mechanisms
underlying these events remain unclear in humans. Here, we identify a subset of
endoglin-expressing endothelial cells enriched in human bone marrow during fetal
ontogeny and upon regeneration after chemotherapeutic injury. Comprehensive
transcriptional characterization by massive parallel RNA sequencing of these
cells reveals a phenotypic and molecular similarity to murine type H endothelium
and activation of angiocrine factors implicated in hematopoiesis, osteogenesis,
and angiogenesis. Interleukin-33 (IL-33) was significantly overexpressed in these
endothelial cells and promoted the expansion of distinct subsets of hematopoietic
precursor cells, endothelial cells, as well as osteogenic differentiation. The
identification and molecular characterization of these human regeneration
associated endothelial cells is thus anticipated to instruct the discovery of
angiocrine factors driving bone marrow formation and recovery after injury.
PMID- 29346766
TI - Cell-Type Specificity of Callosally Evoked Excitation and Feedforward Inhibition
in the Prefrontal Cortex.
AB - Excitation and inhibition are highly specific in the cortex, with distinct
synaptic connections made onto subtypes of projection neurons. The functional
consequences of this selective connectivity depend on both synaptic strength and
the intrinsic properties of targeted neurons but remain poorly understood. Here,
we examine responses to callosal inputs at cortico-cortical (CC) and cortico
thalamic (CT) neurons in layer 5 of mouse prelimbic prefrontal cortex (PFC). We
find callosally evoked excitation and feedforward inhibition are much stronger at
CT neurons compared to neighboring CC neurons. Elevated inhibition at CT neurons
reflects biased synaptic inputs from parvalbumin and somatostatin positive
interneurons. The intrinsic properties of postsynaptic targets equalize
excitatory and inhibitory response amplitudes but selectively accelerate decays
at CT neurons. Feedforward inhibition further reduces response amplitude and
balances action potential firing across these projection neurons. Our findings
highlight the synaptic and cellular mechanisms regulating callosal recruitment of
layer 5 microcircuits in PFC.
PMID- 29346767
TI - Functional Principles of Posterior Septal Inputs to the Medial Habenula.
AB - The medial habenula (MHb) is an epithalamic hub contributing to expression and
extinction of aversive states by bridging forebrain areas and midbrain
monoaminergic centers. Although contradictory information exists regarding their
synaptic properties, the physiology of the excitatory inputs to the MHb from the
posterior septum remains elusive. Here, combining optogenetics-based mapping with
ex vivo and in vivo physiology, we examine the synaptic properties of posterior
septal afferents to the MHb and how they influence behavior. We demonstrate that
MHb cells receive sparse inputs producing purely glutamatergic responses via
calcium-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
(AMPA), heterotrimeric GluN2A-GluN2B-GluN1 N-methyl-D-aspartate (NMDA) receptors,
and inhibitory group II metabotropic glutamate receptors. We describe the complex
integration dynamics of these components by MHb cells. Finally, we combine ex
vivo data with realistic afferent firing patterns recorded in vivo to demonstrate
that efficient optogenetic septal stimulation in the MHb induces anxiolysis and
promotes locomotion, contributing long-awaited evidence in favor of the
importance of this septo-habenular pathway.
PMID- 29346768
TI - Activation of AMPK-Regulated CRH Neurons in the PVH is Sufficient and Necessary
to Induce Dietary Preference for Carbohydrate over Fat.
AB - Food selection is essential for metabolic homeostasis and is influenced by
nutritional state, food palatability, and social factors such as stress. However,
the mechanism responsible for selection between a high-carbohydrate diet (HCD)
and a high-fat diet (HFD) remains unknown. Here, we show that activation of a
subset of corticotropin-releasing hormone (CRH)-positive neurons in the rostral
region of the paraventricular hypothalamus (PVH) induces selection of an HCD over
an HFD in mice during refeeding after fasting, resulting in a rapid recovery from
the change in ketone metabolism. These neurons manifest activation of AMP
activated protein kinase (AMPK) during food deprivation, and this activation is
necessary and sufficient for selection of an HCD over an HFD. Furthermore, this
effect is mediated by carnitine palmitoyltransferase 1c (CPT1c). Thus, our
results identify the specific neurons and intracellular signaling pathway
responsible for regulation of the complex behavior of selection between an HCD
and an HFD. VIDEO ABSTRACT.
PMID- 29346769
TI - Switching On Depression and Potentiation in the Cerebellum.
AB - Long-term depression (LTD) and long-term potentiation (LTP) in the cerebellum are
important for motor learning. However, the signaling mechanisms controlling
whether LTD or LTP is induced in response to synaptic stimulation remain obscure.
Using a unified model of LTD and LTP at the cerebellar parallel fiber-Purkinje
cell (PF-PC) synapse, we delineate the coordinated pre- and postsynaptic
signaling that determines the direction of plasticity. We show that LTP is the
default response to PF stimulation above a well-defined frequency threshold.
However, if the calcium signal surpasses the threshold for CaMKII activation,
then an ultrasensitive "on switch" activates an extracellular signal-regulated
kinase (ERK)-based positive feedback loop that triggers LTD instead. This
postsynaptic feedback loop is sustained by another, trans-synaptic, feedback loop
that maintains nitric oxide production throughout LTD induction. When full
depression is achieved, an automatic "off switch" inactivates the feedback loops,
returning the network to its basal state and demarcating the end of the early
phase of LTD.
PMID- 29346770
TI - Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into
Autism Spectrum Disorder.
AB - Recent studies have established important roles of de novo mutations (DNMs) in
autism spectrum disorders (ASDs). Here, we analyze DNMs in 262 ASD probands of
Japanese origin and confirm the "de novo paradigm" of ASDs across ethnicities.
Based on this consistency, we combine the lists of damaging DNMs in our and
published ASD cohorts (total number of trios, 4,244) and perform integrative
bioinformatics analyses. Besides replicating the findings of previous studies,
our analyses highlight ATP-binding genes and fetal cerebellar/striatal circuits.
Analysis of individual genes identified 61 genes enriched for damaging DNMs,
including ten genes for which our dataset now contributes to statistical
significance. Screening of compounds altering the expression of genes hit by
damaging DNMs reveals a global downregulating effect of valproic acid, a known
risk factor for ASDs, whereas cardiac glycosides upregulate these genes.
Collectively, our integrative approach provides deeper biological and potential
medical insights into ASDs.
PMID- 29346771
TI - Rapid Turnover of Cortical NCAM1 Regulates Synaptic Reorganization after
Peripheral Nerve Injury.
AB - Peripheral nerve injury can induce pathological conditions that lead to
persistent sensitized nociception. Although there is evidence that plastic
changes in the cortex contribute to this process, the underlying molecular
mechanisms are unclear. Here, we find that activation of the anterior cingulate
cortex (ACC) induced by peripheral nerve injury increases the turnover of
specific synaptic proteins in a persistent manner. We demonstrate that neural
cell adhesion molecule 1 (NCAM1) is one of the molecules involved and show that
it mediates spine reorganization and contributes to the behavioral sensitization.
We show striking parallels in the underlying mechanism with the maintenance of
NMDA-receptor- and protein-synthesis-dependent long-term potentiation (LTP) in
the ACC. Our results, therefore, demonstrate a synaptic mechanism for cortical
reorganization and suggest potential avenues for neuropathic pain treatment.
PMID- 29346772
TI - Peroxisome Proliferator Activated Receptor Gamma Controls Mature Brown Adipocyte
Inducibility through Glycerol Kinase.
AB - Peroxisome proliferator-activated receptors (PPARs) have been suggested as the
master regulators of adipose tissue formation. However, their role in regulating
brown fat functionality has not been resolved. To address this question, we
generated mice with inducible brown fat-specific deletions of PPARalpha,
beta/delta, and gamma, respectively. We found that both PPARalpha and
beta/deltadelta are dispensable for brown fat function. In contrast, we could
show that ablation of PPARgamma in vitro and in vivo led to a reduced thermogenic
capacity accompanied by a loss of inducibility by beta-adrenergic signaling, as
well as a shift from oxidative fatty acid metabolism to glucose utilization. We
identified glycerol kinase (Gyk) as a partial mediator of PPARgamma function and
could show that Gyk expression correlates with brown fat thermogenic capacity in
human brown fat biopsies. Thus, Gyk might constitute the link between PPARgamma
mediated regulation of brown fat function and activation by beta-adrenergic
signaling.
PMID- 29346773
TI - Dual Role for DsbA in Attacking and Targeted Bacterial Cells during Type VI
Secretion System-Mediated Competition.
AB - Incorporation of disulfide bonds into proteins can be critical for function or
stability. In bacterial cells, the periplasmic enzyme DsbA is responsible for
disulfide incorporation into many extra-cytoplasmic proteins. The type VI
secretion system (T6SS) is a widely occurring nanomachine that delivers toxic
effector proteins directly into rival bacterial cells, playing a key role in
inter-bacterial competition. We report that two redundant DsbA proteins are
required for virulence and for proper deployment of the T6SS in the opportunistic
pathogen Serratia marcescens, with several T6SS components being subject to the
action of DsbA in secreting cells. Importantly, we demonstrate that DsbA also
plays a critical role in recipient target cells, being required for the toxicity
of certain incoming effector proteins. Thus we reveal that target cell functions
can be hijacked by T6SS effectors for effector activation, adding a further level
of complexity to the T6SS-mediated inter-bacterial interactions which define
varied microbial communities.
PMID- 29346774
TI - Mannose Receptor 1 Restricts HIV Particle Release from Infected Macrophages.
AB - Human mannose receptor 1 (hMRC1) is expressed on the surface of most tissue
macrophages, dendritic cells, and select lymphatic or liver endothelial cells.
HMRC1 contributes to the binding of HIV-1 to monocyte-derived macrophages (MDMs)
and is involved in the endocytic uptake of HIV-1 into these cells. Here, we
identify hMRC1 as an antiviral factor that inhibits virus release through a bone
marrow stromal antigen 2 (BST-2)-like mechanism. Virions produced in the presence
of hMRC1 accumulated in clusters at the cell surface but were fully infectious.
HIV-1 counteracted the effect by transcriptional silencing of hMRC1. The effect
of hMRC1 was not virus isolate specific. Surprisingly, deletion of the Env
protein, which is known to interact with hMRC1, did not relieve the hMRC1
antiviral activity, suggesting the involvement of additional cellular factor(s)
in the process. Our data reveal an antiviral mechanism that is active in primary
human macrophages and is counteracted by HIV-1 through downregulation of hMRC1.
PMID- 29346775
TI - BRD4 Promotes DNA Repair and Mediates the Formation of TMPRSS2-ERG Gene
Rearrangements in Prostate Cancer.
AB - BRD4 belongs to the bromodomain and extraterminal (BET) family of chromatin
reader proteins that bind acetylated histones and regulate gene expression.
Pharmacological inhibition of BRD4 by BET inhibitors (BETi) has indicated
antitumor activity against multiple cancer types. We show that BRD4 is essential
for the repair of DNA double-strand breaks (DSBs) and mediates the formation of
oncogenic gene rearrangements by engaging the non-homologous end joining (NHEJ)
pathway. Mechanistically, genome-wide DNA breaks are associated with enhanced
acetylation of histone H4, leading to BRD4 recruitment, and stable establishment
of the DNA repair complex. In support of this, we also show that, in clinical
tumor samples, BRD4 protein levels are negatively associated with outcome after
prostate cancer (PCa) radiation therapy. Thus, in addition to regulating gene
expression, BRD4 is also a central player in the repair of DNA DSBs, with
significant implications for cancer therapy.
PMID- 29346776
TI - Loss of an Androgen-Inactivating and Isoform-Specific HSD17B4 Splice Form Enables
Emergence of Castration-Resistant Prostate Cancer.
AB - Castration-resistant prostate cancer (CRPC) requires tumors to engage metabolic
mechanisms that allow sustained testosterone and/or dihydrotestosterone to
stimulate progression. 17beta-Hydroxysteroid dehydrogenase type 4 (17betaHSD4),
encoded by HSD17B4, is thought to inactivate testosterone and dihydrotestosterone
by converting them to their respective inert 17-keto steroids.
Counterintuitively, HSD17B4 expression increases in CRPC and predicts poor
prognosis. Here, we show that, of five alternative splice forms, only isoform 2
encodes an enzyme capable of testosterone and dihydrotestosterone inactivation.
In contrast with other transcripts, functional expression of isoform 2 is
specifically suppressed in development of CRPC in patients. Genetically silencing
isoform 2 shifts the metabolic balance toward 17beta-OH androgens (testosterone
and dihydrotestosterone), stimulating androgen receptor (AR) and CRPC
development. Our studies specifically implicate HSD17B4 isoform 2 loss in lethal
prostate cancer.
PMID- 29346777
TI - PRRT2 Regulates Synaptic Fusion by Directly Modulating SNARE Complex Assembly.
AB - Mutations in proline-rich transmembrane protein 2 (PRRT2) are associated with a
range of paroxysmal neurological disorders. PRRT2 predominantly localizes to the
pre-synaptic terminals and is believed to regulate neurotransmitter release.
However, the mechanism of action is unclear. Here, we use reconstituted single
vesicle and bulk fusion assays, combined with live cell imaging of single
exocytotic events in PC12 cells and biophysical analysis, to delineate the
physiological role of PRRT2. We report that PRRT2 selectively blocks the trans
SNARE complex assembly and thus negatively regulates synaptic vesicle priming.
This inhibition is actualized via weak interactions of the N-terminal proline
rich domain with the synaptic SNARE proteins. Furthermore, we demonstrate that
paroxysmal dyskinesia-associated mutations in PRRT2 disrupt this SNARE-modulatory
function and with efficiencies corresponding to the severity of the disease
phenotype. Our findings provide insights into the molecular mechanisms through
which loss-of-function mutations in PRRT2 result in paroxysmal neurological
disorders.
PMID- 29346778
TI - Diverse Brain Myeloid Expression Profiles Reveal Distinct Microglial Activation
States and Aspects of Alzheimer's Disease Not Evident in Mouse Models.
AB - Microglia, the CNS-resident immune cells, play important roles in disease, but
the spectrum of their possible activation states is not well understood. We
derived co-regulated gene modules from transcriptional profiles of CNS myeloid
cells of diverse mouse models, including new tauopathy model datasets. Using
these modules to interpret single-cell data from an Alzheimer's disease (AD)
model, we identified microglial subsets-distinct from previously reported
"disease-associated microglia"-expressing interferon-related or proliferation
modules. We then analyzed whole-tissue RNA profiles from human neurodegenerative
diseases, including a new AD dataset. Correcting for altered cellular composition
of AD tissue, we observed elevated expression of the neurodegeneration-related
modules, but also modules not implicated using expression profiles from mouse
models alone. We provide a searchable, interactive database for exploring gene
expression in all these datasets (http://research
pub.gene.com/BrainMyeloidLandscape). Understanding the dimensions of CNS myeloid
cell activation in human disease may reveal opportunities for therapeutic
intervention.
PMID- 29346779
TI - Predictors of Recoverability of Renal Function after Pyeloplasty in Adults with
Ureteropelvic Junction Obstruction.
AB - BACKGROUND: This study aimed to identify factors predicting the recoverability of
renal function after pyeloplasty in adult patients with ureteropelvic junction
obstruction. METHODS: We retrospectively reviewed 138 adults with unilateral
renal obstruction-induced hydronephrosis and who underwent Anderson-Hynes
dismembered pyeloplasty from January 2013 to January 2016. Hydronephrosis was
classified preoperatively according to the Society for Fetal Urology (SFU)
grading system. All patients underwent Doppler ultrasonography, excretory
urography, computed tomography, and technetium-99m-diethylenetriamine pentaacetic
acid radioisotope (99mTc DTPA) renography before and after surgery. Renal
resistive index (RRI) and 99mTc DTPA renography were repeated at 1, 3, 6, and 12
months. RESULTS: Multivariate analysis identified age, renal pelvic type, SFU
grade, preoperative RRI, decline of RRI, and renal parenchyma to hydronephrosis
area ratio (PHAR) as independent predictors of renal function recoverability
after pyeloplasty. However, preoperative RRI and RRI decline were not
significantly associated with recoverability of renal function in patients aged
>35 years. Lower preoperative RRI, greater decline in RRI, higher PHAR, lower SFU
grade, and extrarenal pelvis were associated with greater improvements in
postoperative renal function. CONCLUSIONS: Preoperative differential renal
function cannot independently predict the recoverability of postoperative renal
function in adult patients with unilateral renal obstruction-induced
hydronephrosis. SFU grade, renal pelvic type, PHAR, preoperative RRI, and decline
in RRI were significantly associated with the recoverability of renal function in
adult patients aged <35 years, while only SFU grade, renal pelvic type, and PHAR
were significantly associated with renal function recoverability in patients aged
>=35 years. Renal function recovery was better in patients younger than 35 years
when compared with older patients.
PMID- 29346780
TI - Prevention of Aortic Dissection Suggests a Diameter Shift to a Lower Aortic Size
Threshold for Intervention.
AB - BACKGROUND: Multiple studies have quantified the relationship between aortic size
and risk of dissection. However, these studies estimated the risk of dissection
without accounting for any increase in aortic size from the dissection process
itself. OBJECTIVES: This study aims to compare aortic size before and after
dissection and to evaluate the change in size consequent to the dissection
itself. METHODS: Fifty-five consecutive patients (29 type A; 26 type B) with
aortic dissection and incidental imaging studies prior to dissection were
identified and compared to a control group of aneurysm patients (n = 205). The
average time between measurement at and prior to dissection was 1.7 +/- 1.9 years
(1.9 +/- 2.0 years mean inter-image time in the control group). A multivariate
regression model controlling for growth rate, age, and gender was created to
estimate the effect of dissection itself on aortic size. RESULTS: The mean aortic
sizes at and prior to dissection were 54.2 +/- 7.0 and 45.1 +/- 5.7 mm for the
ascending aorta, and 47.1 +/- 13.8 and 39.5 +/- 13.1 mm for the descending aorta,
respectively. The multivariable analysis revealed a significant impact of the
dissection itself (p < 0.001) and estimated an increase in size of 7.65 mm
(ascending aorta) and 6.38 mm (descending aorta). Thus, a proportional estimate
of 82.8% (ascending aorta) and 80.8% (descending aorta) of dissections are made
at a size lower than the guideline-recommended threshold (55 mm). CONCLUSIONS:
The aortic diameter increases substantially due to aortic dissection itself and,
thus, aortas are being dissected at clinically meaningfully smaller sizes than
natural history analyses have previously suggested. These findings have important
implications regarding the size at which the risk of dissection is increased.
PMID- 29346781
TI - Laparoscopic Nephron-Sparing Calycectomy for Treating Fraley's Syndrome.
AB - : Background/Aims/Objectives: Various nephron-sparing approaches were described
as part of surgical management for Fraley's syndrome, a rare anatomic variant of
the renal vascular anatomy that compresses the upper pole infundibulum resulting
in an upper calyceal obstruction and dilatation, with symptoms of flank pain and
hematuria. To date, descriptions of minimally invasive correction techniques are
anecdotal. METHODS: A retroperitoneal pure laparoscopic approach using the
nephron-sparing technique was chosen in the presented case. RESULTS: In this
report, we demonstrated that if laparoscopic calycectomy is performed without
clamping of renal branches, parenchymal ischemia can be completely avoided.
Additionally, the preservation of renal tissue surrounding the calyx enables the
preservation of the intrasinusal segmental arteries flow, thereby avoiding their
accidental closure by hemostatic sutures. CONCLUSIONS: In conclusion,
Laparoscopic Nephron-Sparing Calycectomy is a safe and effective surgical
procedure for the treatment of Fraley's syndrome. Consistent laparoscopic
experience is required before embarking on this kind of surgery.
PMID- 29346782
TI - A Fair Chance for Everyone: Total Tumor Volume as a Selection Tool in Liver
Transplantation for Hepatocellular Carcinoma.
AB - : Total tumor volume (TTV) has been proposed as a more accurate means of
selecting patients for liver transplantation (LT) due to hepatocellular carcinoma
(HCC). We aim to analyze the role of TTV in a population with a short waiting
time on list. METHODS: Analysis of a prospective database of patients submitted
to LT for HCC between September 1992 and February 2014. TTV, Milan criteria (MC),
UCSF (University of California San Francisco), and "Up to Seven" criteria were
calculated both with preoperative imaging exams and histological data. RESULTS:
The study population consisted of 231 out of patients. Median waiting time on
list was 62.5 days. MC included 187 patients, while TTV <=115 cm3 included 214.
Microvascular invasion (HR 2.601, 95% CI 1.529-4.426), MC (HR 1.666, 95% CI 0.990
2.804), UCSF criteria (HR 2.995, 95% CI 1.875-4.875), TTV <=115 cm3 (HR 2.898,
95% CI 1.398-6.007), and "Up to Seven" criteria (HR 2.139, 95% CI 1.353-3.383)
proved to be independent factors for prognosis for disease-free survival.
CONCLUSIONS: TTV <=115 cm3 may be a useful tool to properly identify the best HCC
candidates for LT in a population with a short waiting time on list. TTV gives
more patients the opportunity of undergoing LT while maintaining similar rates of
tumor recurrence and patient survival.
PMID- 29346783
TI - Does [-2]Pro-Prostate Specific Antigen Meet the Criteria to Justify Its Inclusion
in the Clinical Decision-Making Process?
AB - INTRODUCTION: To assess whether [-2]pro-prostate-specific antigen (p2PSA) meets
the criteria to justify its inclusion in a predictive model of prostate cancer
(PCa) diagnosis and in the clinical decision-making process. MATERIALS AND
METHODS: A total 172 men with total prostate-specific antigen of 2-10 ng/mL
underwent measurement of free PSA and p2PSA before prostate biopsy in an
observational and prospective study. From these measurements, the Prostate Health
Index (PHI) was calculated. Clinical and analytical predictive models were
created incorporating PHI. RESULTS: Of 172 men, 72 (42%) were diagnosed with PCa,
33 (46%) of whom were found to be with high-grade disease. PHI score was the most
predictive of biopsy outcomes in terms of discriminative ability (area under the
curve = 0.79), with an added gain in predictive accuracy of 17%. All the models
that incorporated PHI worked better in terms of calibration close to 45 degrees
on the slope. In the decision curve analysis, at a threshold probability of 40%
we could prevent 82 biopsies, missing only 16 tumors and 5 high-grade tumors.
CONCLUSIONS: PHI score is a more discriminant biomarker, has superior calibration
and superior net benefit, and provides a higher rate of avoided biopsies; thus,
it can be useful for aiding in making a more informed decision for each patient.
PMID- 29346784
TI - Surgical Treatment and Chemotherapy of Adult Primary Liver Sarcoma: Experiences
from a Single Hospital in China.
AB - BACKGROUND: The aim of this study is to improve the preoperative diagnostic
accuracy and treatment results by investigating the clinical features and
prognosis of primary liver sarcoma (PLS). METHODS: Clinical data, surgical
treatments, adjuvant chemotherapy, and prognosis of 17 PLS patients whose
diseases were pathologically confirmed were retrospectively analyzed. RESULTS:
The main clinical symptoms included epigastric pain in 9 patients, epigastric
distention in 7, and loss of appetite in 4; these symptoms were detected during
the postoperative follow-up for gastric carcinoma in 1. The resection rate was
64.7% (12/17), including R0 resection in 10 patients and R1 resection in 2, and
laparotomy with biopsy in 5. Five patients accepted an adjuvant selective hepatic
artery infusion chemotherapy (mitomycin C 16-20 mg+ 5-fluorouracil 5.0 g+
epirubicin 40-50 mg), and 4 accepted adjuvant systemic chemotherapy (vincristin,
cisplatin, cyclophosphamide, and adriamycin). All 5 patients with simple
laparotomy died within 1 year, and the overall 1-, 3-, and 5-year survival rates
for all patients were 58.8% (10/17), 29.4% (5/17) and 11.7% (2/17), respectively,
whereas those were 100.0% (10/10), 50.0% (5/10), and 20.0% (2/10) for R0 resected
patients respectively. CONCLUSIONS: The diagnosis of PLS is difficult before
operation due to its nonspecific manifestations, and the high survival rate can
be achieved by radical resection with adjuvant chemotherapy.
PMID- 29346785
TI - Impulsivity and Saliva Cortisol in Patients with Suicide Attempt and Controls.
AB - OBJECTIVES: The objective of this study was to prove concepts in the
characterization of suicidal patients and the possible usefulness of those
markers to potentially identify patients with a higher risk for suicidality.
METHODS: Patients with a recent suicide attempt were compared with patients
suffering from depression, adjustment disorder, anxiety, or eating disorders
without suicidality, healthy controls and remitted patients with a history of at
least 1 suicide attempt (>=1 year). We analyzed impulsivity (Barratt Impulsivity
Scale, BIS) and saliva cortisol concentrations. RESULTS: Independently of
suicidality and disease state patients display higher BIS scores than healthy
controls. Saliva cortisol levels tend to be higher in patients in the acute
disease state than in remitted patients and healthy controls. CONCLUSIONS: Saliva
cortisol may be a useful marker that reveals alterations in nonsuicidal patients
suffering from depression, adjustment disorder, anxiety, or eating disorders who
might be at risk.
PMID- 29346786
TI - Changing Trends in Brain Imaging Technique for Pediatric Patients with
Ventriculoperitoneal Shunts.
AB - BACKGROUND: Children with ventriculoperitoneal shunts (VPS) undergoing brain
computed tomography (CT) for shunt malfunction evaluation are at risk for later
malignancy due to radiation exposure. We aimed to determine if and how hospitals
have adopted radiation-avoiding magnetic resonance imaging (MRI) techniques.
METHODS: We performed a secondary analysis of the Pediatric Health Information
System (PHIS) database. Children with VPS presenting to acute wards at 31 PHIS
hospitals between January 1, 2007 and January 2, 2015 and receiving noncontrast
neuroimaging on day of service 0/1 were included. Outcome measures were (1)
incidence of MRI over time and (2) comparison of demographic characteristics
between hospitals with MRI representing higher versus lower proportions (>15% or
<15%) of total brain imaging. RESULTS: MRIs increased by 18.1% from 2007 to 2015.
Hospitals were assigned to high-use (n = 12) or minimal-use (n = 19) MRI groups
based on year 2014/2015 MRI percentages. The only identified difference was an
older mean age in the high-use group (8.1 vs. 7.5 years; p = 0.03). CONCLUSIONS:
MRI is increasingly used to evaluate patients with VPS. Hospitals with more MRI
use had older patients and no increase in cost or length of stay. Initiating
local quality improvement projects may help identify barriers to MRI uptake and
increase use.
PMID- 29346787
TI - Speech and Communication Changes Reported by People with Parkinson's Disease.
AB - BACKGROUND: Changes in communicative functions are common in Parkinson's disease
(PD), but there are only limited data provided by individuals with PD on how
these changes are perceived, what their consequences are, and what type of
intervention is provided. AIM: To present self-reported information about speech
and communication, the impact on communicative participation, and the amount and
type of speech-language pathology services received by people with PD. METHODS:
Respondents with PD recruited via the Swedish Parkinson's Disease Society filled
out a questionnaire accessed via a Web link or provided in a paper version.
RESULTS: Of 188 respondents, 92.5% reported at least one symptom related to
communication; the most common symptoms were weak voice, word-finding
difficulties, imprecise articulation, and getting off topic in conversation. The
speech and communication problems resulted in restricted communicative
participation for between a quarter and a third of the respondents, and their
speech caused embarrassment sometimes or more often to more than half. Forty-five
percent of the respondents had received speech-language pathology services.
CONCLUSIONS: Most respondents reported both speech and language symptoms, and
many experienced restricted communicative participation. Access to speech
language pathology services is still inadequate. Services should also address
cognitive/linguistic aspects to meet the needs of people with PD.
PMID- 29346788
TI - Vitamin D: Classic and Novel Actions.
AB - BACKGROUND: Classically, vitamin D has been implicated in bone health by
promoting calcium absorption in the gut and maintenance of serum calcium and
phosphate concentrations, as well as by its action on bone growth and
reorganization through the action of osteoblasts and osteoclasts cells. However,
in the last 2 decades, novel actions of vitamin D have been discovered. The
present report summarizes both classic and novel actions of vitamin D. SUMMARY:
1,25(OH)2 vitamin D, the active metabolite of vitamin D, also known as
calcitriol, regulates not only calcium and phosphate homeostasis but also cell
proliferation and differentiation, and has a key a role to play in the responses
of the immune and nervous systems. Current effects of vitamin D include
xenobiotic detoxification, oxidative stress reduction, neuroprotective functions,
antimicrobial defense, immunoregulation, anti-inflammatory/anticancer actions,
and cardiovascular benefits. The mechanism of action of calcitriol is mediated by
the vitamin D receptor, a subfamily of nuclear receptors that act as
transcription factors into the target cells after forming a heterodimer with the
retinoid X receptor. This kind of receptors has been found in virtually all cell
types, which may explain its multiple actions on different tissues. Key Messages:
In addition to classic actions related to mineral homeostasis, vitamin D has
novel actions in cell proliferation and differentiation, regulation of the innate
and adaptative immune systems, preventive effects on cardiovascular and
neurodegenerative diseases, and even antiaging effects.
PMID- 29346789
TI - Mentalization and Self-Efficacy as Mediators between Psychological Symptom
Severity and Disabilities in Activities and Participation in Psychotherapy
Patients.
AB - BACKGROUND: Psychotherapy patients can be more or less disabled by their
psychological symptoms. The present study investigated whether mentalization and
self-efficacy contribute to the association between psychological symptom
severity and disabilities in activities and participation. METHODS: The data of
216 psychotherapy inpatients were examined in a cross-sectional design.
Bootstrapping-enhanced mediation analyses were performed to investigate whether
self-efficacy and mentalization are mediators between psychological symptom
severity and disabilities in activities and participation. The Hamburg Modules
for the Assessment of Psychosocial Health-49 were used to measure psychological
symptom severity and self-efficacy, mentalization was assessed with the
Mentalization Questionnaire, and disabilities in activities and participation
were operationalized with the ICF-Mental-A & P questionnaire. RESULTS:
Mentalization as well as self-efficacy functioned as mediators between
psychological symptom severity and disabilities in activities and participation
(p < 0.05). They were equally strong mediators, and both remained significant
mediators when statistically controlling for the other mediator (p < 0.05).
CONCLUSIONS: Mentalization as well as self-efficacy explain a significant
proportion of the relationship between psychological symptom severity and
disabilities in activities and participation. Working on mentalizing and self
efficacy might be important mechanisms to reduce disability due to symptoms. The
cross-sectional design is a limitation of the study.
PMID- 29346790
TI - Multivisceral Resection for Locally Invasive Colorectal Liver Metastases:
Outcomes of a Matched Cohort Analysis.
AB - : Local invasion of adjacent viscera by colorectal liver metastases (CRLM) is no
longer considered an absolute contraindication to curative hepatic resection. A
growing number of observational analyses have illustrated the feasibility of such
resections; however, the evidence base is at best heterogeneous with a lack of
evidence comparing similar patient groups. We aimed to evaluate the outcomes of
hepatectomy for CRLM when combined with other viscera and compare to a matched
cohort of isolated hepatic resections. METHODS: From 2005 to 2015, 523 patients
underwent hepatic resection for CRLM at our institution, 19 of whom underwent
hepatectomy with extrahepatic resection. A 3: 1 matched cohort analysis was
performed between those who underwent isolated hepatectomy (control group) and
those who underwent hepatectomy with extrahepatic resection (combined group).
Clinicopathological data were reviewed along with 30-day postoperative morbidity
and mortality. Furthermore, overall survival for the multivisceral cohort was
compared to all other isolated hepatectomies over the same time period. RESULTS:
Nineteen patients underwent liver resection accompanied by either/or
diaphragmatic resection (n = 13), major vein resection and reconstruction (n =
5), and visceral resection (n = 3). Maximum tumor size was significantly larger
in the combined group (60.58 vs. 15.34 mm p < 0.0001). Postoperative morbidity
was similar in both groups (p = 0.41). Following multivisceral resection, 1-, 3-
and 5-year survival rates were 75, 56.6, and 25.7% respectively. Overall survival
showed no significant difference between combined and control groups (p = 0.78).
Similarly, when compared to the total cohort of isolated liver resections (n =
504), no significant difference in overall mortality was noted. CONCLUSION: In
patients presenting with concomitant CRLM and extrahepatic extension where R0
margins can be achieved, this present study supports the rationale to proceed to
surgery with comparable morbidity and mortality rates to -isolated hepatectomy.
PMID- 29346792
TI - Pancreaticoduodenectomy and Outcomes for Groove Pancreatitis.
AB - BACKGROUND/AIMS: The operative management of groove pancreatitis (GP) is still a
matter of controversy and pancreaticoduodenectomy (PD) can be a high-risk
procedure for patients. The aim of this study was to report our 9-year experience
of surgical resection for GP and to review relevant literature. METHODS: A
retrospective review of patients undergoing pancreatectomy for GP from August 1,
2008, through May 31, 2017 was performed. Patients with clinical, radiologic, and
final pathologic confirmation of GP were included. Literature on the current
understanding of GP was reviewed. RESULTS: Eight patients from total 449
pancreatectomies met inclusion criteria. Four male and 4 female patients (mean
age, 51.9 years; mean body mass index, 25.3) underwent pylorus-preserving
pancreatoduodenectomy (3 by laparoscopy and 5 by open approach). Mean (range)
operative time and blood loss was 343 (167-525) min and 218 (40-500) mL
respectively. Pancreatic fistula and delayed gastric emptying were noted in one
patient each. No major complications occurred, but minor complications occurred
in 5 (62%) patients. Mean hospital stay was 6.1 (range 3-14) days. At median
follow-up of 18.15 (interquartile range 7.25-33.8) months, all patients
experienced a resolution of pancreatitis and improvement in symptoms.
CONCLUSIONS: PD is a safe procedure for GP. Short-term surgical outcomes are
acceptable and long-term outcomes are associated with improved symptom control.
PMID- 29346791
TI - Social and Behavioural Determinants of the Difference in Survival among Older
Adults in Japan and England.
AB - BACKGROUND: A rapidly ageing population presents major challenges to health and
social care services. Cross-country comparative studies on survival among older
adults are limited. In addition, Japan, the country with the longest life
expectancy, is rarely included in these cross-country comparisons. OBJECTIVE: We
examined the relative contributions of social and behavioural factors on the
differences in survival among older people in Japan and England. METHODS: We used
data from the Japan Gerontological Evaluation Study (JAGES; n = 13,176) and the
English Longitudinal Study of Ageing (ELSA; n = 5,551) to analyse all-cause
mortality up to 9.4 years from the baseline. Applying Laplace regression models,
the 15th survival percentile difference was estimated. RESULTS: During the follow
up, 31.3% of women and 38.6% of men in the ELSA died, whereas 19.3% of women and
31.3% of men in the JAGES died. After adjusting for age and baseline health
status, JAGES participants had longer survival than ELSA participants by 318.8
days for women and by 131.6 days for men. Family-based social relationships
contributed to 105.4 days longer survival in JAGES than ELSA men. Fewer
friendship-based social relationships shortened the JAGES men's survival by 45.4
days compared to ELSA men. Currently not being a smoker contributed to longer
survival for JAGES women (197.7 days) and ELSA men (46.6 days), and having lower
BMI reduced the survival of JAGES participants by 129.0 days for women and by
212.2 days for men. CONCLUSION: Compared to participants in England, Japanese
older people lived longer mainly because of non-smoking for women and family
based social relationships for men. In contrast, a lower rate of underweight,
men's better friendship-based social relationships, and a lower smoking rate
contributed to survival among participants in England.
PMID- 29346793
TI - Epicardial Fat Thickness in Non-Obese Neurologically Impaired Children:
Association with Unfavorable Cardiometabolic Risk Profile.
AB - BACKGROUND: Cardiovascular risk is reported in disabled children and epicardial
fat (EF) is considered an independent predictor of cardiovascular disease (CVD).
No data on the EF thickness (EFT) evaluation in disabled children have been
published. OBJECTIVE: We investigated EFT in neurologically impaired (NI)
children; its relationship with their metabolic profile was also considered.
METHODS: Clinical data, body composition estimation, biochemical profile, and
ultrasound-measured EFT were performed in 32 disabled patients (12.4 +/- 6.3
years). Pathological parameters were defined using the following criteria: waist
circumference >95th percentile, waist to height ratio (WHtR) >0.5, total
cholesterol and triglycerides (TG) values >95th percentile, high density
lipoprotein cholesterol <5th percentile, fasting blood glucose >100 mg/dL,
homeostasis model assessment for insulin resistance (HOMA) >97.5th percentile,
and EFT >3.6 mm. RESULTS: EFT values in NI children were higher compared with
control group values (p = 0.02). EFT correlated with gender (p < 0.001), age (p =
0.02), pubertal stage (p = 0.04), as well as WHtR (p = 0.03). A correlation
between EFT and leptin was also noted (p = 0.04). EFT levels significantly
correlated with pathological TG (p = 0.01) and HOMA-IR (p = 0.04). CONCLUSIONS:
Higher EFT was observed in NI children compared with controls. EFT values
correlated with clinical, metabolic, and endocrinological parameters. Ultrasound
measured EFT could be used to promptly detect subclinical CVD and to prevent
adverse outcomes in disabled children.
PMID- 29346795
TI - Hello, Goodbye!
PMID- 29346794
TI - Clinicoepidemiologic Features of Chronic Urticaria in Patients with versus
without Subclinical Helicobacter pylori Infection: A Cross-Sectional Study of 150
Patients.
AB - BACKGROUND: The Helicobacter pylori infection is linked to chronic urticaria in
nearly 60% of patients. We studied clinicoepidemiologic features in patients with
chronic urticaria with and without H. pylori infection. METHODS: Endoscopic
antral biopsy for the rapid urease test (RUT) and histopathology, and serum IgG
ELISA for H. pylori infection were performed in 150 patients (male:female ratio
1:2.4) of chronic urticaria aged 18-68 years. Clinicoepidemiologic features
including age, gender, age of onset and duration, frequency and distribution of
wheals, urticaria severity score, and systemic symptoms were analyzed in patients
with and without H. pylori. The results of serum IgG ELISA for H. pylori were
compared with 106 age- and gender-matched healthy adult controls. RESULTS: The
RUT in 84 patients (56%), histopathology in 76 patients (50.6%), and H. pylori
IgG ELISA in 94 patients (62.6%) were positive. H. pylori IgG ELISA was positive
only in 35 (33%) controls, suggesting that chronic urticaria patients were more
likely to have asymptomatic H. pylori infection than normal controls. Although
not statistically significant, patients with H. pylori had a higher mean
urticaria severity score, number of urticaria/angioedema episodes per year, and
involvement of more body sites, particularly the scalp, palms, and soles. The
constitutional or gastrointestinal symptoms were statistically higher in patients
with H. pylori infection than those without it. CONCLUSION: A subset of chronic
urticaria patients appears to have asymptomatic H. pylori infection. However, its
implications in chronicity, recurrences, the severity of urticaria, other
systemic manifestations, and management remains conjectural in view of 33% of
controls also having positive H. pylori ELISA and the endemicity of infection in
developing countries.
PMID- 29346796
TI - Background Factors and Subjective Voice Symptoms in Patients with Acquired Vocal
Fold Scarring and Sulcus Vocalis.
AB - OBJECTIVE: Vocal fold scarring (VFS) and sulcus vocalis (SV) often result in
severe and chronic voice disorders. This study compares subjective voice
complaints as rated with the Voice Handicap Index and etiological factors for
patients with VFS and SV. PATIENTS AND METHODS: Data were collected from the
medical records at the Department of Otorhinolaryngology, Karolinska University
Hospital, for 27 VFS patients and 27 SV patients. Descriptive background factors
were compared between the groups and data were compared from the Swedish Voice
Handicap Index (Sw-VHI) questionnaires. RESULTS: Previous laryngeal
surgery/trauma was significantly more common for the patients with VFS. The SV
group had significantly more persistent dysphonia since childhood. It was
significantly more common to have a non-Germanic language origin among the SV
patients. VFS and SV rated high for the total median Sw-VHI scores. The VFS
group's total Sw-VHI and the three domain scores were significantly higher
compared to the SV group. The physical domain showed a significantly higher score
when compared to the functional and emotional domains in the SV cohort and when
compared to the emotional domain in the VFS cohort. CONCLUSION: There are
significant differences between the VFS group and SV group regarding etiological
factors as well as the Sw-VHI. The degree and profile of VHI should be considered
when selecting patients and evaluating the result of new treatments for this
group of patients.
PMID- 29346797
TI - Aortic Size and Aortic Dissection: Does One Size Fit All?
PMID- 29346798
TI - Uric Acid in the Follow-Up Determines 30% Decline in Estimated GFR Over 2 Years:
a Propensity Score Analysis.
AB - BACKGROUND/AIMS: Higher level of serum uric acid (SUA) predicts early entry to
dialysis in chronic kidney disease (CKD) patients. However, a short-term effect
of SUA remains to be elucidated using a novel surrogate endpoint. METHODS:
Japanese CKD stage 3 to 4 patients were retrospectively examined (n= 701). The
follow-up level of SUA was estimated as time-averaged uric acid (TA-UA). A
propensity score for 6.0, 6.5 or 7.0 mg/dL of TA-UA was respectively calculated
using baseline 23 covariates. The time-to-event analysis was performed for 30%
decline in estimated GFR over 2 years. RESULTS: Incidence rates over 2 years were
90 of 440 in men and 36 of 261 in women (p = 0.03). Despite the negative result
of baseline SUA, stratified Cox regression on the quintiles of the estimated
propensity score showed that higher TA-UA of the three thresholds were all
significant (crude HR 2.10 to 2.44) even after adjusting for the confounders.
Kaplan-Meier analysis after propensity score matching likewise showed worse
survival in the patients with the higher TA-UA (HR 3.11 to 4.26). CONCLUSION:
Higher SUA increases likelihood of reaching a surrogate endpoint over 2 years.
Early intervention for SUA less than 6.0 mg/dL is recommended for slowing CKD
progression.
PMID- 29346799
TI - Call for Nomination of Members of the International Standing Committee of Human
Cytogenomic Nomenclature.
PMID- 29346800
TI - Correction: Key differences between 13 KRAS mutation detection technologies and
their relevance for clinical practice.
AB - [This corrects the article DOI: 10.1136/esmoopen-2017-000235.][This corrects the
article DOI: 10.1136/esmoopen-2017-000235.].
PMID- 29346801
TI - Early Gene Expression Profile in Retinal Ganglion Cell Layer After Optic Nerve
Crush in Mice.
AB - Purpose: Optic nerve crush (ONC) induces retinal ganglion cell (RGC) death, which
causes vision loss in glaucoma. To investigate early events leading to apoptosis
of RGCs, we performed gene expression analysis of injured retinas in the period
before RGC loss. Methods: The temporal changes of gene profiles at 0, 1, and 4
days after ONC were determined by DNA microarray. To verify the gene expression
changes in RGCs, we enriched RGCs by laser-captured microdissection and performed
real-time RT-PCR of 14 selected genes. In situ localization study was performed
by immunohistochemistry. Results: At 1 day and 4 days after ONC, 1423 and 2010
retinal genes were changed compared with 0 day, respectively; these genes were
mainly related to apoptotic process, immune process, regulation of cell cycle,
and ion transport. RT-PCR analysis revealed that expression levels of Activating
transcription factor 3 (Atf3), Lipocalin 2 (Lcn2), and tumor necrosis factor
receptor superfamily member 12a (Tnfrsf12a) were remarkably changed in RGC
enriched fraction within 4 days postcrush. Immunohistochemical analysis confirmed
that all of these genes expressed highly in the ganglion cell layer of crushed
retinas. Conclusions: In response to ONC, the expression of apoptotic genes was
stimulated soon after crush. Atf3, Lcn2, and Tnfrsf12a might be key molecules
responsible for RGC loss in glaucoma.
PMID- 29346802
TI - Penetrance of the LHON Mutation m.11778G>A May Depend on Factors Other Than the
Haplotype or Heteroplasmy Rate.
PMID- 29346803
TI - Author Response: Penetrance of the LHON Mutation m.11778G>A May Depend on Factors
Other Than Haplotype or Heteroplasmy Rate.
PMID- 29346805
TI - Mesenteric Vessel Patency Following HIFU Therapy in Patients with Locally
Invasive Pancreatic Cancer.
AB - PURPOSE: To evaluate the effects of HIFU therapy on visceral vessel patency in
patients with inoperable locally invasive pancreatic cancer. MATERIALS AND
METHODS: 50 pancreatic cancer patients (26 men, 24 women) aged 41 - 82 years
(65.0 +/- 10.2) underwent ultrasonography (US) and computed tomography (CT)
examinations before and within one day after HIFU treatment, as well as at follow
up at six weeks, three months and six months. Evaluation and grading were
performed by two experienced independent radiologists according to a
classification scheme based on vessel involvement, vessel diameter, patency, and
defects in flow. RESULTS: Before HIFU treatment, arterial vessel involvement was
noted in 42 patients, venous involvement in 47, and 47 patients presented with
both. Superior mesenteric artery occlusion was found in three carcinomas while
nearly half of the cases (n = 24) displayed signs of superior mesenteric vein,
portal vein, or splenic vein occlusion. High-grade tumor-associated arterial
narrowing was seen in ten patients. Despite vessel encasement and partially
extensive propagation of collateral vessels, it was possible to safely perform
HIFU treatment in all patients without complications. US and CT studies performed
within one day after therapy did not show any change in vessel patency in 47
patients (94 %). Follow-up controls at the six-week mark revealed increased
vessel narrowing and finally occlusion after six months in 11 patients due to
tumor progression. CONCLUSION: This study demonstrates that HIFU treatment can
be safely applied to pancreatic cancers enveloping large mesenteric vessels
despite vessel narrowing or extensive collateral propagation. Most patients (94
%) did not experience adverse effects regarding vessel patency.
PMID- 29346804
TI - Trabodenoson, an Adenosine Mimetic With A1 Receptor Selectivity Lowers
Intraocular Pressure by Increasing Conventional Outflow Facility in Mice.
AB - Purpose: To evaluate the relationship between the IOP-lowering effect of
trabodenoson and the associated structural and functional changes in the
trabecular meshwork (TM). Methods: Six independent cohorts of young and aged mice
were exposed to three different topical once-a-day formulations of trabodenoson
and eyes were compared to those treated with placebo drops. IOP was measured
daily just before drug administration using rebound tonometry. Outflow facility
was measured in enucleated eyes. Flow patterns and morphology of conventional
outflow tissues were monitored using tracer beads and standard histology,
respectively. In parallel, three-dimensional human TM tissue constructs (3D-HTM)
were grown and used in experiments to test effect of trabodenoson on the
expression of collagen IV, fibronectin, matrix metalloproteinase (MMP)-2 and MMP
14 plus MMP-2 activity. Results: Topical administration of trabodenoson
significantly lowered IOP on every day tested, up to 7 days. After 2 days of
treatment, outflow facility increased by 26% in aged mice and 30% overall (young
and aged mice), which was significantly different from vehicle (P < 0.05).
Outflow facility was 15% higher than controls after 7 days of treatment (P =
0.07). While gross morphology was not affected by treatment, the intensity of
tracer bead distribution increased by day 7 (P = 0.05). Parallel experiments in
3D-HTM showed that trabodenoson treatment significantly increased MMP-2 activity
and MMP-14 abundance, while decreasing fibronectin and collagen IV expression.
Conclusions: Trabodenoson alters ECM turnover by TM cells and increases
conventional outflow facility, which accounts for its ability to lower IOP in
young and aged mice.
PMID- 29346806
TI - Lithium and Renal Impairment: A Review on a Still Hot Topic.
AB - INTRODUCTION: Lithium is established as an effective treatment of mania, of
depression in bipolar and unipolar disorder, and in maintenance treatment of
these disorders. However, due to the necessity of monitoring and concerns about
irreversible adverse effects, in particular renal impairment, after long-term
use, lithium might be underutilized. METHODS: This study reviewed 6 large
observational studies addressing the risk of impaired renal function associated
with lithium treatment and methodological issues impacting interpretation of
results. RESULTS: An increased risk of renal impairment associated with lithium
treatment is suggested. This increased risk may, at least partly, be a result of
surveillance bias. Additionally, the earliest studies pointed toward an increased
risk of end-stage renal disease associated with lithium treatment, whereas the
later and methodologically most sound studies do not. DISCUSSION: The improved
renal outcome found in the more recent lithium studies may be a result of
improved monitoring and focus on recommended serum levels (preferentially 0.6-0.8
mmol/L) as compared to poorer renal outcome in studies with patients treated in
the 1960s to 1980s.
PMID- 29346807
TI - Anti-Angiogenic Activity of Rotenoids from the Stems of Derris trifoliata.
AB - The plants in the genus Derris have proven to be a rich source of rotenoids, of
which cytotoxic effect against cancer cells seem to be pronounced. However, their
effect on angiogenesis playing a crucial role in both cancer growth and
metastasis has been seldom investigated. This study aimed at investigating the
effect of the eight rotenoids (1: -8: ) isolated from Derris trifoliata stems on
three cancer cells and angiogenesis. Among them, 12a-hydroxyrotenone (2: )
exhibited potent inhibition on both cell growth and migration of HCT116 colon
cancer cells. Further, anti-angiogenic assay in an ex vivo model was carried out
to determine the effect of the isolated rotenoids on angiogenesis. Results
revealed that 12a-hydroxyrotenone (2: ) displayed the most potent suppression of
microvessel sprouting. The in vitro assay on human umbilical vein endothelial
cells was performed to determine whether compound 2: elicits anti-angiogenic
effect and its effect was found to occur via suppression of endothelial cells
proliferation and tube formation, but not endothelial cells migration. This study
provides the first evidence that compound 2: could potently inhibit HCT116 cancer
migration and anti-angiogenic activity, demonstrating that 2: might be a
potential agent or a lead compound for cancer therapy.
PMID- 29346808
TI - ?
PMID- 29346809
TI - ?
PMID- 29346810
TI - [POEMS Syndrome].
PMID- 29346811
TI - ?
PMID- 29346812
TI - ?
PMID- 29346813
TI - ?
PMID- 29346814
TI - ?
PMID- 29346815
TI - ?
PMID- 29346816
TI - ?
PMID- 29346817
TI - ?
PMID- 29346818
TI - ?
PMID- 29346819
TI - ?
PMID- 29346820
TI - ?
PMID- 29346821
TI - ?
PMID- 29346822
TI - ?
PMID- 29346823
TI - ?
PMID- 29346824
TI - Antimicrobial Chemotherapy has a Linear Relationship to the Proportion of Gram
Negative Isolates from Pediatric Burn Wounds.
AB - : Wound infection in burns is a relevant cause of morbidity and mortality in
children. We aimed to determine the relationship between antibacterial
chemotherapy and Gram-negative burn wound colonization and infection. All
children admitted to the pediatric intensive care unit for burn trauma from June
1, 2005 to January 31, 2013 were included. We obtained 141 wound samples, of
which 88 (65.7%) showed growth of Gram-positive bacteria. Treatment with
antimicrobial chemotherapy was necessary in 23 (31.1%) patients. The proportion
of Gram-negative isolates seems to increase linear from 12.5% (95% confidence
interval (CI): 4.4%-28.7%) without antibacterial chemotherapy to 36.8% (95% CI:
25.5%-49.6%) with one to 48.9% (95% CI: 35.3%-62.8%) with 2 antimicrobial agents.
The Odds ratio for a Gram-negative isolate, in comparison to patients without
antibacterial chemotherapy, increased from 4.083 (95% CI: 1.140-15.961) for one
administered substance to 6.708 (95% CI: 1.832-26.786) if 2 or more were used.
CONCLUSION: We found that antibacterial chemotherapy seems to facilitate burn
wound colonization and results in an increased number of gram-negative isolates
from children with burn wounds.
PMID- 29346825
TI - Magnetic Resonance Imaging of Articular Cartilage within the Knee.
AB - Magnetic resonance imaging (MRI) provides an effective and noninvasive means by
which to evaluate articular cartilage within the knee. Existing techniques can be
utilized to detect and monitor longitudinal changes in cartilage status due to
injury or progression of degenerative disease. Quantitative MRI (qMRI) techniques
can provide a metric by which to evaluate the efficacy of cartilage repair
techniques and offer insight into the composition of cartilage and cartilage
repair tissue. In this review, we provide background on MR signal generation and
decay, the utility of morphologic MRI assessment, and qMRI techniques for the
biochemical assessment of cartilage (dGEMRIC, T2, T2*, T1rho, sodium, gagCEST).
Finally, the description and utility of these qMRI techniques for the evaluation
of cartilage repair are discussed.
PMID- 29346826
TI - Gastroduodenal intussusception and pylorus obstruction induced by a c-KIT
negative gastric gastrointestinal stromal tumor: case report and review of the
literature.
AB - INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are infrequently reported
to cause gastroduodenal intussusception, especially in the cases with complete
pylorus obstruction. GISTs comprise only 1 - 3 % of all gastrointestinal tract
tumors, and most of them strongly express the c-KIT protein. Approximately 5 % of
GISTs show negative staining of c-KIT. CASE PRESENTATION: A 69-year-old man
complained of acute abdominal pain accompanied with nausea and vomiting for 6
hours. Emergency endoscopic examination, upper gastroenterography, and computed
tomography scan suggested gastroduodenal intussusception and pylorus obstruction
induced by a gastric GIST. Laparoscopic exploration and wedge resection of the
tumor were performed in the patient. Postoperative histological examination
showed a gastric GIST with c-KIT-negative expression. CONCLUSION: Herein, we
report the unique findings of a c-KIT-negative gastric GIST presenting with
gastroduodenal intussusception and pylorus obstruction. We also reviewed the
English language literature of gastroduodenal intussusception induced by GISTs
and put our case in the context of the previously reported cases.
PMID- 29346827
TI - Efficacy and complications of submucosal tunneling endoscopic resection for upper
gastrointestinal submucosal tumors and exploration for influencing factors.
AB - BACKGROUND: Submucosal tunneling endoscopic resection (STER) has emerged as a
feasible technique for resecting upper gastrointestinal (GI) tract submucosal
tumors (SMTs) through natural orifice transluminal endoscopic surgery. STER
reduces the risk of postoperative perforation and abdominal infections and
promotes rapid wound healing. The aim of this meta-analysis was to evaluate the
safety and efficacy of STER for small (<= 3.5 cm) upper GI SMTs and explore the
potential factors influencing STER's efficacy and complication rate. METHODS:
Comprehensive literature searches were performed to find studies on STER for
removal of SMTs. Several English-language databases were searched, including
MEDLINE (through PubMed), EMBASE, and the Cochrane Library for the period January
2010 to June 2016. The medical terms "submucosal tunneling endoscopic resection
or STER", "upper gastrointestinal", and "submucosal tumors" were used in the
search. The primary outcome measures were the pooled estimates of the complete
resection and en bloc resection rates. The secondary outcome measure was the
pooled estimate of complications. RESULT: Twelve studies including 397 patients
and 430 lesions were identified. The pooled estimate of the complete resection
rate was 98.1 % (95 % confidence interval [CI]: 95.9 - 99.2 %). The pooled
estimate of en bloc resection was 94.9 % (95 % CI: 91.1 - 97.1 %). The pooled
estimate of gas-related complications such as pneumoperitoneum and subcutaneous
emphysema was 21.5 % (95 % CI: 13.2 - 33.1 %). The pooled estimate of
inflammation-related complications including pleural and abdominal effusion was
8.4 % (95 % CI: 5.6 - 12.3 %). Gas-related complications occurred more frequently
in the esophagogastric junction than in the stomach. In addition, the pooled
estimate of delayed bleeding was 2.2 % (95 % CI: 1.0 - 4.7 %). CONCLUSION: STER
appeared to be an extremely effective technique for removing upper GI SMTs
originating from the muscularis propria layer. In addition, the very low rate of
complications also shows the safety of this technique. Tumor size, infiltration
depth, and location may influence the complication rates.
PMID- 29346828
TI - Dynamic Posterior Stabilization versus Posterior Lumbar Intervertebral Fusion: A
Matched Cohort Study Based on the Spine Tango Registry.
AB - PURPOSE: The primary aim of dynamic stabilization is to stabilize the spine and
preserve function without overstressing adjacent segments, which is a potential
risk of fusion surgery. However, direct comparative analyses of the two
approaches are still limited, and little is known about the association of
patient-reported outcomes with these treatment options. OBJECTIVE: To compare
the clinical outcomes of dynamic posterior stabilization using the DSS
Stabilization System (Paradigm Spine, LLC, New York, New York, United States)
versus posterior lumbar intervertebral fusion (PLIF) based on data from a spine
registry. We hypothesized that patient-reported outcomes of DSS are not inferior
to those of PLIF. METHODS: We identified 202 DSS and 269 PLIF patients with
lumbar degenerative disease with a minimum 2-year follow-up. A 1:1 propensity
score-based matching was applied to balance the groups for various patient
characteristics. The primary outcome was the change in the patient-reported Core
Outcome Measures Index (COMI; a 0-10 scale) score. RESULTS: The matching
resulted in 77 DSS-PLIF pairs (mean age: 67 years; average COMI follow-up: 3.3
years) without residual significant differences in baseline characteristics. The
groups showed no difference in improved COMI score (p = 0.69), as well as in back
(p = 0.51) and leg pain relief (p = 0.56), blood loss (p = 0.12), and
complications (p > 0.15). Fewer repeat surgeries occurred after DSS (p = 0.01).
The number of repeat surgeries per 100 observed person-years was 0.8 and 2.9 in
DSS and in PLIF patients, respectively. Furthermore, shorter surgery time (p <
0.001) and longer hospital stays (p = 0.03) were observed for DSS cases.
CONCLUSION: In a midterm perspective, DSS may be a viable alternative to PLIF
because both therapies result in similar COMI score improvement. Advantages of
DSS may be shorter duration of surgery and fewer repeat surgeries. However, more
than half of DSS patients did not find a match with a PLIF patient, suggesting
that the patient profiles may be different. Further multicenter studies are
needed to better understand the most appropriate indication for each therapy.
PMID- 29346830
TI - Feasibility of Navigable Percutaneous Disk Decompressor (L'DISQ-C) for Cervical
Disk Herniation.
AB - OBJECTIVE: To assess the procedural efficacy and safety of a Navigable
Percutaneous Disk Decompressor (L'DISQ-C) for cervical disk herniation. METHODS:
We performed intradiskal decompression on cervical spine specimens from five
human cadavers using the L'DISQ-C under C-arm fluoroscopic guidance. We evaluated
our success for positioning the navigable wand tip into the target region and
recorded temperature variation at various distances from the wand tip in the
cervical nucleus pulposus. The histologic effect of plasma decompression was
examined microscopically using harvested tissues adjacent to the procedure site.
RESULTS: We successfully navigated the tip of the L'DISQ-C into the target
region of the posterior cervical disks on the first insertion attempt in all C3
C4 to C6-C7 disks and in 50% of the C2-C3 and C7-T1 disks. The average
temperature elevations within the nucleus pulposus ranged from 4.14 +/- 0.08
degrees C to 12.17 +/- 0.76 degrees C at various distances from the wand tip with
or without saline infusion. A histologic examination showed only minor
denaturation at the marginal border of the procedure tract. CONCLUSION: We
effectively navigated the L'DISQ-C wand tip into the posterior target region of
six cadaveric cervical disks and performed percutaneous resection of the target
disk tissues without significant thermal or structural damage to adjacent
tissues.
PMID- 29346829
TI - Intraoperative Seizures in Awake Craniotomy for Perirolandic Glioma Resections
That Undergo Cortical Mapping.
AB - BACKGROUND: Perirolandic motor area gliomas present invasive eloquent region
tumors within the precentral gyrus that are difficult to resect without causing
neurologic deficits. STUDY AIMS: This study evaluates the role of awake
craniotomy and motor mapping on neurologic outcome and extent of resection (EOR)
of tumor in the perirolandic motor region. It also analyzes preoperative risk
factors for intraoperative seizures. METHODS: We evaluated 57 patients who
underwent an awake craniotomy for a perirolandic motor area eloquent region
glioma. Patients who had positive mapping (PM) or intraoperative identification
of motor regions in the cortex using direct cortical stimulation were compared
with patients with no positive motor mapping following direct cortical
stimulation and negative mapping (NM). Preoperative risks, intraoperative
seizures, perioperative outcomes, tumor characteristics, and EOR were also
compared. A logistic regression model was used to evaluate the predictors for
intraoperative seizures in this patient cohort. RESULTS: Overall, 33 patients
were in the PM cohort; 24 were in the NM cohort. Our study showed an 8.8%
incidence of intraoperative seizures during cortical and subcortical mapping for
awake craniotomies in the perirolandic motor area, none of which aborted the
case. PM patients had significantly more intraoperative and postoperative
seizures (15.5% and 30.3%, respectively) compared with the NM patients (0% and
8.3%, respectively; p = 0.046 and 0.044). New transient postoperative motor
deficits were found more often in the PM group (51.5%) versus the NM group
(12.5%; p = 0.002). A univariate logistic regression showed that PM (odds ratio
[OR]: 1.16; 95% confidence interval [CI], 1.01-1.34; p = 0.035) and preoperative
tumor volume (OR: 0.998; 95% CI, 0.996-0.999; p = 0.049) were significant
predictors for intraoperative seizures in patients with perirolandic gliomas.
CONCLUSION: Awake craniotomies in the perirolandic motor region can be safely
performed with a similar incidence of intraoperative seizures as reported for the
language cortex. PM in this region may increase the likelihood of perioperative
seizures or motor deficits compared with NM. Craniotomies that minimize cortical
exposure for perirolandic gliomas that may not localize motor regions can still
allow for extensive tumor resection with a good postoperative outcome.
PMID- 29346831
TI - Postoperative Reduction of Intraventricular Hemorrhage Volume: Single- Versus
Dual-Catheter Drainage.
AB - BACKGROUND/AIMS: The use of single/dual external ventricular drains (EVD) for
reducing intraventricular hemorrhage (IVH) is under investigation. A randomized
controlled trial was conducted to compare postoperative reduction of IVH volume
using single- and dual-catheter drainage in spontaneous IVH patients. We
investigated factors that may influence an effective hematoma volume reduction by
EVDs. MATERIALS AND METHODS: The average cerebrospinal fluid (CSF) drainage
volumes were analyzed. Computed tomography (CT) scans were performed on
admission, 24 hours and 48 hours after EVD placement, and then on days 5 and 8.
Patient group 1 was treated with a single EVD; patient group 2 was treated with
bilateral EVDs. The IVH volume was calculated in all ventricles. A multivariate
analysis was conducted to investigate variables that can influence the extent of
hematoma volume reduction with a bilateral EVD. Regression followed by a Pearson
correlation was performed to observe the strength of association of cofounders
with the IVH volume reduction. RESULTS: The percentage of IVH volume change was
found to be significantly higher in the dual-catheter group compared with the
single-catheter group (p = 0.0034) after 5 days of EVD. The mean reduction in IVH
volume was 17.36 (mL) in patients <= 45 years of age and 20.50 (mL) in patients >
45 years. The multivariate analysis suggested the following significant
predictors for IVH volume reduction: age of the patient (p = 0.011) and longer
duration (days) of EVD (p = 0.028). The age of the patient had a weak positive
association and duration of EVD had a positive association with the IVH volume
reduction. CONCLUSION: Intraventricular drainage via bilateral EVDs may provide
a better draining of blood-mixed CSF because it led to faster clot clearance. It
is suggested that a longer duration of bilateral EVDs may lead to a greater
reduction in IVH volume. Older patients may experience a greater IVH volume
reduction by EVD because the volume of CSF increases with cerebral atrophy.
PMID- 29346832
TI - Diagnosis of Lumbar Spinal Stenosis with Functional Myelography.
AB - BACKGROUND AND STUDY AIMS: The diagnosis of a lumbar spinal stenosis demands
advanced diagnostic radiologic techniques. In recent decades magnetic resonance
imaging (MRI) has replaced myelography, now considered an old-fashioned
technique. It was our hypothesis that functional myelography still plays an
important role in selected cases. We investigated how our surgical strategy was
influenced by the results of MRI, functional myelography, and postmyelography
computed tomography (CT) in patients with a lumbar spinal stenosis. METHODS: The
sagittal diameters of the lumbar spinal canal were measured from L1 to S1 on
patients with lumbar spinal stenosis. MRI, functional myelography, and
postmyelography CT were compared in each of the patients. Sensitivity and
specificity were calculated in each method. We examined how the surgical strategy
was influenced by the results of these different methods. RESULTS: Fifty
consecutive patients (21 women and 29 men; mean age: 70 years, [range: 49-86
years]) fulfilled the inclusion criteria. Functional myelography revealed a
sensitivity of 0.99, a specificity of 0.79, and a positive predictive value of
0.45. The MRI exhibited a sensitivity of 0.93, a specificity of 0.74, and a
positive predictive value of 0.39. Postmyelography CT showed a sensitivity of
0.96, a specificity of 0.75, and a positive predictive value of 0.41. A
functional myelography revealed more information than the MRI and resulted in a
change in the surgical strategy in 11 of 50 patients (22%) in comparison with the
sole results of MRI or a postmyelography CT. CONCLUSIONS: In selected cases with
multilevel lumbar spinal stenosis, functional myelography revealed the highest
precision in reaching a correct diagnosis. It resulted in a change in the
surgical approach in every fifth patient in comparison with the MRI and proved
most helpful, especially in elderly patients.
PMID- 29346833
TI - Phase 1b Trial of Ficlatuzumab, a Humanized Hepatocyte Growth Factor Inhibitory
Monoclonal Antibody, in Combination With Gefitinib in Asian Patients With NSCLC.
AB - Hepatocyte growth factor (HGF)/c-Met pathway dysregulation is a mechanism for
epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs).
Ficlatuzumab (AV-299; SCH 900105), a humanized IgG1 kappa HGF inhibitory
monoclonal antibody, prevents HGF/c-Met pathway ligand-mediated activation. This
phase 1b study assessed the safety/tolerability,
pharmacokinetics/pharmacodynamics, and antitumor activity of ficlatuzumab plus
gefitinib in Asian patients with previously treated advanced non-small cell lung
cancer (NSCLC). Patients received intravenous ficlatuzumab either 10 mg/kg
(cohort 1; n = 3) or 20 mg/kg (cohort 2; n = 12) every 2 weeks plus oral
gefitinib 250 mg daily. Patients tolerated the drug combination well. Four
treatment-related grade 3/4 adverse events were reported in 3 patients (cohort
2). Pharmacokinetic profiles for ficlatuzumab and gefitinib were consistent with
prior single-agent trials. Partial responses were achieved in 5 patients (4
confirmed), all in cohort 2; objective response rate (ORR) was 33% (duration, 1.9
6.4 months). Responding patients had no prior EGFR TKI treatment, 2 without an
EGFR mutation. Four additional patients had disease stabilization (cohort 2;
duration, 2.7-9.1 months; 42% ORR). The recommended phase 2 dose for ficlatuzumab
plus gefitinib 250 mg/day was 20 mg/kg every 2 weeks. This drug combination has
shown preliminary dose-related antitumor activity in advanced NSCLC.
PMID- 29346834
TI - Twelve-week ravidasvir plus ritonavir-boosted danoprevir and ribavirin for non
cirrhotic HCV genotype 1 patients: A phase 2 study.
AB - BACKGROUND AND AIM: The need for all-oral hepatitis C virus (HCV) treatments with
higher response rates, improved tolerability, and lower pill burden compared with
interferon-inclusive regimen has led to the development of new direct-acting
antiviral agents. Ravidasvir (RDV) is a second-generation, pan-genotypic NS5A
inhibitor with high barrier to resistance. The aim of this phase 2 study (EVEREST
study) was to assess the efficacy and safety of interferon-free, 12-week RDV plus
ritonavir-boosted danoprevir (DNVr) and ribavirin (RBV) regimen for treatment
naive Asian HCV genotype 1 (GT1) patients without cirrhosis. METHODS: A total of
38 treatment-naive, non-cirrhotic adult HCV GT1 patients were enrolled in this
multicenter, open-label, single-arm phase 2 study (NCT03020095). All patients
received a combination of RDV 200 mg once daily (q.d.) plus DNVr 100 mg/100 mg
twice daily (b.i.d.) and oral RBV 1000/1200 mg/day (body weight < 75/>= 75 kg)
for 12 weeks. The primary endpoint was the rate of sustained virologic response
12 weeks after the end of treatment (SVR12). RESULTS: Of 38 patients, all (100%)
achieved SVR12. During the study, no treatment-related serious adverse events, no
patients discontinued treatment due to adverse events, and no deaths were
reported. Six of 37 (16%) patients with available sequences had HCV NS5A
resistance-associated variants at baseline. All patients (6/6) with baseline NS5A
resistance-associated variants achieved SVR12. CONCLUSIONS: Twelve-week RDV and
DNVr in combination with RBV for 12 weeks achieves the SVR12 rate of 100% in
treatment-naive non-cirrhotic Asian patients with HCV GT1 infection. This
interferon-free regimen is also safe and well tolerated.
PMID- 29346835
TI - Two citrate transporters coordinately regulate citrate secretion from rice bean
root tip under aluminum stress.
AB - Aluminum (Al)-induced organic acid secretion from the root apex is an important
Al resistance mechanism. However, it remains unclear how plants fine-tune root
organic acid secretion which can contribute significantly to the loss of fixed
carbon from the plant. Here, we demonstrate that Al-induced citrate secretion
from the rice bean root apex is biphasic, consisting of an early phase with low
secretion and a later phase of large citrate secretion. We isolated and
characterized VuMATE2 as a possible second citrate transporter in rice bean
functioning in tandem with VuMATE1, which we previously identified. The time
dependent kinetics of VuMATE2 expression correlates well with the kinetics of
early phase root citrate secretion. Ectopic expression of VuMATE2 in Arabidopsis
resulted in increased root citrate secretion and Al resistance.
Electrophysiological analysis of Xenopus oocytes expressing VuMATE2 indicated
VuMATE2 mediates anion efflux. However, the expression regulation of VuMATE2
differs from VuMATE1. While a protein translation inhibitor suppressed Al-induced
VuMATE1 expression, it releases VuMATE2 expression. Yeast one-hybrid assays
demonstrated that a previously identified transcription factor, VuSTOP1,
interacts with the VuMATE2 promoter at a GGGAGG cis-acting motif. Thus, we
demonstrate that plants adapt to Al toxicity by fine-tuning root citrate
secretion with two separate root citrate transport systems.
PMID- 29346836
TI - Emergency demand, repeat and frequent presentations by older patients in
metropolitan Melbourne: A retrospective cohort study using routinely collected
hospital data.
AB - OBJECTIVE: To describe patterns for potentially avoidable general practice (PAGP)
type and non-PAGP-type ED presentations by older patients during 2008 and 2012.
METHODS: Retrospective analysis of ED presentations by patients >=70 years for
2008 and 2012. Metropolitan Melbourne public hospital data were obtained from the
Victorian Emergency Minimum Dataset. Outcomes were characteristics of PAGP-type
and non-PAGP-type presentations as defined by the Australian Institute of Health
and Welfare; numbers and rates per 1000 population >=70 years of repeat (*2
3/year) and frequent (>= *4/year) PAGP-type and non-PAGP-type presentations.
RESULTS: The older metropolitan Melbourne population increased by 10.3% between
2008 and 2012, whereas the number of ED presentations increased by 12.7%. The
volume of PAGP-type presentations decreased by 2.6%, with declining rates per
1000 population >=70 years of repeat (7.2-6.2) and frequent (0.7-0.4)
presentation. In contrast, the volume of non-PAGP-type presentations grew by
15.4%, with increasing repeat (57.6-60.7) and frequent (13.1-14.2) presentation
rates per 1000 population >=70 years. The majority (39%) of non-PAGP-type
presentations by frequent ED attenders were due to cardiovascular or respiratory
problems. CONCLUSION: The rate of repeat and frequent PAGP-type presentations by
older people decreased in 2012 compared with 2008, suggesting that initiatives
implemented to reduce avoidable presentations may have had an effect. However, an
increase in the rate of frequent non-PAGP-type presentations, predominately for
acute exacerbation of cardiovascular and respiratory conditions, has important
implications for planning future healthcare delivery; hence, the importance of
initiatives such as the Health Care Home.
PMID- 29346837
TI - A Phase 1, Randomized, Placebo- and Active-Controlled Crossover Study to
Determine the Effect of Single-Dose Ertugliflozin on QTc Interval in Healthy
Volunteers.
AB - Ertugliflozin, a selective sodium-glucose cotransporter-2 inhibitor, is being
developed for the treatment of type 2 diabetes mellitus. This randomized, 6
sequence, 3-period crossover study assessed the effect of ertugliflozin (100 mg;
supratherapeutic dose) vs placebo and moxifloxacin (400 mg; positive control) on
the QT interval corrected for heart rate (QTc) in 42 male or female healthy
subjects. Triplicate electrocardiograms were performed predose and serially over
48 hours postdose in each treatment period. The maximum observed least-squares
mean (90% CI) difference in QTc using the Fridericia correction (QTcF) between
ertugliflozin and placebo was 2.99 (1.68, 4.30) milliseconds, 24 hours postdose,
below the 5-millisecond threshold of potential clinical concern. The upper limits
of the 2-sided 90% CI were less than 10 milliseconds at all postdose time points.
The lower 90% CIs for the least-squares mean QTcF difference between moxifloxacin
and placebo were greater than 5 milliseconds at the preselected time points of 2,
3, and 4 hours postdose, establishing study sensitivity. The majority of adverse
events were mild in severity. In healthy volunteers, at a supratherapeutic dose
of 100 mg, ertugliflozin was not associated with QTc interval prolongation.
PMID- 29346839
TI - Prepared for the future.
PMID- 29346840
TI - Into the future.
PMID- 29346838
TI - First-in-human study to assess the safety, pharmacokinetics and pharmacodynamics
of BMS-962212, a direct, reversible, small molecule factor XIa inhibitor in non
Japanese and Japanese healthy subjects.
AB - AIMS: The aims of the present study were to assess the safety, pharmacokinetics
(PK) and pharmacodynamics (PD) of BMS-962212, a first-in-class factor XIa
inhibitor, in Japanese and non-Japanese healthy subjects. METHODS: This was a
randomized, placebo-controlled, double-blind, sequential, ascending-dose study of
2-h (part A) and 5-day (part B) intravenous (IV) infusions of BMS-962212. Part A
used four doses (1.5, 4, 10 and 25 mg h-1 ) of BMS-962212 or placebo in a 6:2
ratio per dose. Part B used four doses (1, 3, 9 and 20 mg h-1 ) enrolling
Japanese (n = 4 active, n = 1 placebo) and non-Japanese (n = 4 active, n = 1
placebo) subjects per dose. The PK, PD, safety and tolerability were assessed
throughout the study. RESULTS: BMS-962212 was well tolerated; there were no signs
of bleeding, and adverse events were mild. In parts A and B, BMS-962212
demonstrated dose proportionality. The mean half-life in parts A and B ranged
from 2.04 to 4.94 h and 6.22 to 8.65 h, respectively. Exposure-dependent changes
were observed in the PD parameters, activated partial thromboplastin time (aPTT)
and factor XI clotting activity (FXI:C). The maximum mean aPTT and FXI:C change
from baseline at 20 mg h-1 in part B was 92% and 90%, respectively. No difference
was observed in weight-corrected steady-state concentrations, aPTT or FXI:C
between Japanese and non-Japanese subjects (P > 0.05). CONCLUSION: BMS-962212 has
tolerability, PK and PD properties suitable for investigational use as an acute
antithrombotic agent in Japanese or non-Japanese subjects.
PMID- 29346841
TI - Granulomatous interstitial nephritis associated with silica.
PMID- 29346842
TI - Dapagliflozin associated ketoacidosis: A must know fact for nephrologists.
PMID- 29346843
TI - Misdiagnosed as osteosarcoma: Brown tumour in a haemodialysis patient.
PMID- 29346844
TI - Conversion of renal abstracts to papers: Published or perished?
PMID- 29346845
TI - A New Approach to the Evaluation of Local Muscular Load while Typing on a
Keyboard.
AB - OBJECTIVE: The aim of this study was to assess the contribution of using
keystroke dynamics (KD) in combination with integrated electromyography (iEMG)
for the objective evaluation of local muscular load of hands and forearms while
typing on a computer keyboard and to compare it with results of the commonly used
method. METHOD: Study was performed on 12 subjects. Data were collected using our
own application for capturing KD data and using EMG Holter for detecting
electromyographic potentials to determine local muscular load. RESULTS: The
results of our study revealed that currently used methods for assessment of the
workload while typing on a computer keyboard are not entirely accurate. In
particular, the real total number of keystrokes performed during processing of a
text is significantly higher than the count of characters the text is consisting
of. In addition to this count, also the so-called invisible keys, keyboard
shortcuts, and especially corrections in the typed text must be taken into
consideration. CONCLUSIONS: The results indicated that all probands in our study
exceeded the valid hygienic limits for the total amount of the small repetitive
movements of the hands and forearms and the total amount of the keyboard typing
movements. Most of the probands in our study also exceeded the valid hygienic
limit for the highest average time-weighted value of the percent maximum
voluntary contraction (%MVC). This implies that the keystroke dynamics method has
a great potential to increase the accuracy of evaluation of local muscular load
when using the keyboard and thus to improve the existing methodology for
investigation of occupational diseases resulting from overload while working on
the computer.
PMID- 29346846
TI - Legislative Norms to Control Cannabis Use in the Light of Its Prevalence in Czech
Republic, Poland, Slovakia, and Hungary.
AB - OBJECTIVES: Cannabis control legislation ranks among key measures to prevent
social-health impacts of its use. The article qualitatively analyses respective
legislation in the Czech Republic, Poland, Slovakia, and Hungary (Visegrad Four,
V4) considering level of decriminalisation of cannabis use in relation to current
epidemiological situation. METHODS: Qualitative analysis of the cannabis control
legislation in V4 countries from 1995 to 2016 focusing on criminal liability,
differentiation of cannabis from other illicit substances, definition of a small
amount intended for personal use, sentences for possessing and dealership of the
drug. Results: Slovakia, Hungary and Poland share similar restrictive legislative
approach throughout the studied period. In the Czech Republic, the situation has
been different and since 2010 cannabis has been further decriminalised:
possession of defined small amount of drug not being under prosecution and milder
sentences for cannabis than for other illicit psychoactive substances. RESULTS:
Slovakia, Hungary and Poland share similar restrictive legislative approach
throughout the studied period. In the Czech Republic, the situation has been
different and since 2010 cannabis has been further decriminalised: possession of
defined small amount of drug not being under prosecution and milder sentences for
cannabis than for other illicit psychoactive substances. CONCLUSION: Although the
prevalence of cannabis use among adolescents is the highest in the Czech
Republic, partial decriminalisation did not show further increase. Slovakia,
Hungary and Poland show different trends in epidemiological situation despite of
similar legislative approach. Results indicate that beside legislation other
social factors play a role and measures to change attitudes and decrease social
tolerance are important.
PMID- 29346847
TI - Manner of Death of Older People with Regard to Blood Alcohol Concentration.
AB - OBJECTIVE: Alcohol abuse is related to a wide variety of negative health outcomes
including mortality in older people. Alcohol abuse in older people is
characterised by certain specific features uncommon in general adult population.
The main objective of this study was to analyse the autopsy protocols of deceased
older people in relation to blood alcohol concentration (BAC), sex, age, and
manner of death. As a positive BAC, >0.20 g/kg was accepted. METHODS: The sample
consists of 1,012 deceased older people (i.e. aged 65 years and over) selected
out of 2,377 autopsied subjects in the period from 2003-2013. Subjects included
into the sample were chosen via the proportional sampling method. Data (BAC, sex,
age, and manner of death) was recorded in a single structured protocol. Data was
evaluated statistically (Kolmogorov-Smirnov two-sample test, Wilcoxon two-sample
test, risk ratio). RESULTS: Among older people, there has been a statistically
significant correlation of natural death with sex (men died earlier) and with
increased BAC (people with positive BAC died earlier). In case of violent death
there is a difference in the types of accidents in older people with positive BAC
(>0.2 g/kg) and with negative BAC (<=0.2 g/kg). Drowning is more common in older
people with positive BAC. CONCLUSIONS: Health campaigns in Europe and the Czech
Republic aimed at reducing alcohol consumption mainly deal with young people.
Alcohol abuse has an impact on premature mortality even in older people. As shown
by this study, older people with positive BAC die significantly earlier.
PMID- 29346848
TI - Factors Influencing Suicidal Tendencies of Patients with Diagnosis of Attempted
Suicide in Medical History and Potential Prevention of Relapse Prevention.
AB - OBJECTIVE: The authors researched the incidence of suicidal thoughts and related
factors in 123 patients of the psychiatric ward of the Hospital of Ceske
Budejovice with diagnosed attempted suicide in their medical history for the
period from January 2013 - June 2015. METHODS: The research was carried out in
two stages. At the beginning of the hospitalization, quantitative data collection
was implemented using a semi-structured questionnaire, followed by qualitative
research conducted with semi-structured phone conversation, based on previous
patient's written consent. The research data were statistically processed to
obtain information about the character of relations among individual
characteristics. To quantify them, the Bayesian Network (BN) was constructed, and
to identify relations among individual characteristics, the Hill-Climbing
algorithm was used. Before deriving the network, variables were discretized. The
network parameters were set based on a data matrix using the maximal plausibility
method. RESULTS: The results of analysed set show that the probability of
suicidal thoughts is high, achieving a value of 0.750 (0.781 for women and 0.724
for men). If the patient visits a contact centre for drug-addicted persons, the
probability of suicidal thoughts decreases to 0.683. If the patient visits a
psychotherapist, the values of 0.736 are achieved. If a daily care centre is
visited, the estimated risk rises to 0.832 and the probability of the patient
repetitively attempting suicide is 0.606. If the interviewed person regularly
consumes alcohol, the probable relapse amounts to 0.616. But if the person
consumes alcohol from time to time, the probability rises to 0.701. In case of
abstinence, the probable relapse decreases to 0.565. CONCLUSIONS: The incidence
of suicidal thoughts in observed patients was high, and the amount of risk was
influenced by gender, by visiting follow-up care facilities, psychotherapy, and
particularly by the frequency of alcohol consumption. Intermittent alcohol
consumption is the highest-risk factor in connection with relapsing suicide. In
case of psychiatric patients with attempted suicide in their medical history, all
verified preventive and therapeutic procedures that can contribute to prevention
of relapses should be used within follow-up professional care. Specific approach
of the closest social environment, medical literacy of the population and state
safety measures are important.
PMID- 29346849
TI - Syphilis Resurgence in Belgrade, Serbia, in the New Millennium: An Outbreak in
2014.
AB - OBJECTIVE: A worldwide syphilis incidence increase was recorded at the beginning
of the new millennium, occurring primarily among men who have sex with men (MSM).
The aim of this study was to analyse the epidemiological situation of syphilis in
the Belgrade population between 2005 and 2014 and to examine the characteristics
of an early syphilis outbreak among MSM in Belgrade in 2014. METHOD: Reporting of
syphilis is compulsory in Serbia. Routinely reported data were analysed along
with data collected from patients' charts. RESULTS: During the period observed,
syphilis incidence increased from 1.07 per 100,000 in 2005 to 4.1 per 100,000 in
2014 (383.2%). From 2005 to 2009, syphilis rates in Belgrade were low, around 1
case per 100,000 people. The first outbreak was registered in 2010. The new
incidence increase happened in 2012, and again in 2014 when it was the highest.
These incidence changes were registered mainly in men, where the frequency of
syphilis was much higher than in women. In 2014, primary syphilis was diagnosed
in 20 cases, secondary syphilis in 42, and early latent syphilis in 9 patients.
Fifty-seven were MSM, 10 were heterosexual men and 4 were women. Twenty-four
cases, all MSM were co-infected with HIV. Majority of patients acquired infection
in Belgrade, while in 42/71 cases oral sex was the only risk factor. In
comparison with HIV negative, HIV positive syphilis patients were older, more
frequently unemployed and MSM. They also more frequently had sex with unknown
partners and were diagnosed in the secondary stage of infection. CONCLUSIONS:
Study results underline the need for coordinated and expeditious surveillance,
partner services, enhanced screening of population at risk, health education, as
well as early diagnosis and treatment.
PMID- 29346850
TI - Trends in the Minimum Inhibitory Concentrations of Erythromycin, Clarithromycin,
Azithromycin, Ciprofloxacin, and Trimethoprim/Sulfamethoxazole for Strains of
Bordetella pertussis isolated in the Czech Republic in 1967-2015.
AB - OBJECTIVE: The aim of the study was to determine trends in the minimum inhibitory
concentrations (MICs) of erythromycin used as first-line therapy and alternative
antibiotics against Bordetella pertussis (B. pertussis) strains isolated from
patients with whooping cough in the Czech Republic (CR) in three periods from
1967 to 2015. METHODS: In total, 135 isolates from the years 1967-2015 were
analysed. The strains were divided into three groups by the year of isolation:
1967-1999 (42 strains), 2004-2010 (43 strains), and 2011-2015 (50 strains). MIC
of selected antibiotics (erythromycin, clarithromycin, azithromycin,
ciprofloxacin, and trimethoprim/sulfamethoxazole) were obtained by the reference
agar dilution method on Bordet Gengou Agar with 15% defibrinated sheep blood.
RESULTS: The study set included 70 strains previously tested for MICs of
erythromycin and four other antibiotics. In the three study periods, the MICs of
the tested antibiotics for B. pertussis were nearly identical. All but a single
strain, inhibited by erythromycin at a concentration of 0.03 mg/l, were inhibited
by two concentrations of erythromycin and azithromycin (0.06 and 0.125 mg/l).
Clarithromycin inhibited the strains from all three study periods at the
following concentrations: 0.03, 0.06, and 0.125 mg/l. Any of the 135 strains was
inhibited by ciprofloxacin at a single concentration of 0.06 mg/l and by
trimethoprim/sulfamethoxazole at three concentrations (0.125, 0.25, and 0.5
mg/l). CONCLUSION: The study set of 135 Czech strains of B. pertussis isolated in
1967-2015 appears to be homogeneous in terms of the MICs for five antimicrobials.
The MICs remained in a narrow range of two to three low concentrations; the
unimodal distribution of the MICs suggests the absence of resistance mechanisms.
The highest MICs of erythromycin, clarithromycin, and azithromycin were equally
0.125 mg/l, that of ciprofloxacin was 0.06 mg/l, and that of
trimethoprim/sulfamethoxazole was 0.5 mg/l. Over the study period of 55 years,
the MICs of the study antibiotics remained in the same ranges.
PMID- 29346851
TI - A Nurse-Led School-Based Sun Protection Programme in Turkey.
AB - OBJECTIVE: The aim of this study was to determine the effects of a nurse-led
school-based sun protection programme in Turkey. METHODS: A randomized controlled
trial was performed at two public schools between February and October 2014.
Children with written consent from their parents were screened by nurses for skin
type, and 80 children at moderate to high risk for skin cancer were included in
the study. The sample was randomized by age, gender and skin type. Stratified and
block randomizations were used. The participants were separated into an
intervention group (n=40) and control group (n=40). Data were collected using a
personal information form and two scales for sun protection behaviour and self
efficacy. RESULTS: In the intervention group, the pretest mean score for sun
protection behaviour was 19.25+/-5.44 and increased significantly in the posttest
assessment (33.05+/-4.23, p<0.001). Self-efficacy scores also increased
significantly after the intervention (pretest 20.50+/-6.68, post-test 35.85+/
4.70, p<0.001). However, there were no significant increases in mean sun
protection behaviour or self-efficacy scores in the control group (p>0.05).
CONCLUSION: A nurse-led school-based sun protection programme effectively
promoted children's self-efficacy and sun protection behaviour.
PMID- 29346852
TI - Symptomatic Response of the Elderly with Cardiovascular Disease during a Heat
Wave in Slovenia.
AB - OBJECTIVE: The aim of this study is to analyse the symptomatic response of
elderly people to heat burden and indoor air quality exposure, and to create an
index, the basis on which healthcare workers could react and prevent heat-related
illnesses when the first symptoms appear. METHODS: The impact of the indoor
thermal environment was studied with regards to Humidex and indoor air quality by
CO2 concentrations on elderly people's symptomatic response. It was a natural
experiment in which two different groups of elderly people (>65 years) were
observed: the first group had a diagnosed cardiovascular disease, and the second
group did not have the disease. RESULTS: The results show that the expression and
aggravation of symptoms are related to an increase of heat burden and low indoor
air quality. The symptoms under analysis do not have the same frequency
distribution of intensity and, therefore, cannot be interpreted as a single
universal symptom index. Instead, two indices must be created separately for both
general and specific symptoms. CONCLUSIONS: Healthcare workers should be educated
about the interactive influences of the thermal environment and the air quality
on health. Unsuitable conditions could be ascertained by the nursing home
occupants' symptomatic response.
PMID- 29346853
TI - Selected Cardiovascular Risk Markers in Vegetarians and Subjects of General
Population.
AB - OBJECTIVE: Besides genetic factors there are environmental effects including
nutritional habits which can influence the risk of age-related diseases. The aim
of the study was to assess the age dependence of selected cardiovascular risk
markers in two groups of subjects with different nutritional pattern. METHODS: In
470 long-term vegetarians and 478 subjects of general population the following
indicators were measured: total cholesterol, HDL-cholesterol, triacylglycerol,
glucose, insulin concentrations, LDL-cholesterol, atherogenic index and insulin
resistance IR(HOMA) were also calculated in studied subjects. Obtained data were
evaluated according to age decades. RESULTS: Vegetarian vs. non-vegetarian
concentrations of total cholesterol, LDL-cholesterol, insulin, and values of
atherogenic index and IR(HOMA) were significantly reduced in all age decades.
Vegetarian vs. non-vegetarian triacalglycerol concentrations were significantly
reduced from 4th-7th decade. Vegetarian average decade values of all lipid
parameters were in reference range. In non-vegetarian group, the risk average
values of total cholesterol (>5.2 mmol/l) were found from 5th-7th decade, LDL
cholesterol (>3.3 mmol/l) in 7th decade and atherogenic index (>4) in 6th-7th
decade. In vegetarians vs. non-vegetarians were noted the average decade values
for total cholesterol ranging from 4.01-4.59 vs. 4.48-5.67 mmol/l, for
triacylglycerols 1.00-1.33 vs. 1.13-1.74 mmol/l, for LDL-cholesterol 2.03-2.58
vs. 2.43-3.49 mmol/l, for atherogenic index 2.72-3.31 vs. 3.05-4.21 and for
IR(HOMA) 0.99-1.15 vs. 1.15-1.84. CONCLUSION: Our data show significantly reduced
mean age decade values of lipid and non-lipid cardiovascular risk markers in all
adult vegetarians. Smaller changes of markers between decades compared to non
vegetarians document a protective effect of vegetarian nutrition in prevention of
cardiovascular disease.
PMID- 29346854
TI - High Participation Rate in Mammography Screening: Experience from Croatia.
AB - OBJECTIVE: The aim of the study was to analyse the results of three cycles of
mammography screening (MS) in the Croatian National Programme (CNP) for Early
Breast Cancer Detection for women aged 50-69 years in the Bjelovar-Bilogora
County (BBC) from 2006-2014. METHODS: Data on women aged 50-69 screened during a
9-year period were obtained from the Croatian Cancer Registry and Institute of
Public Health reports. Participation rate and performance indicators were
examined. RESULTS: The total of 57,428 women were invited to mammography
screening in BBC during a 9-year period and 31,402 mammograms in total were
performed. The response rate of 84% in BBC was consistently higher than the
national average of about 60% reported in 2007, 2013 and 2014. CONCLUSION: The
National Programme in BBC has been carried out continuously for nine years with a
higher response rate compared with the national average, as a result of
additional efforts of the Croatian Institute of Public Health team, as well as
good cooperation among all programme stakeholders. It was concluded that to
achieve better results in the response of women to screening and consequently
reduced mortality from breast cancer is possible through tailored health
promotion activities.
PMID- 29346855
TI - Do Adolescents with T1DM Differ from Their Peers in Health, Eating Habits and
Social Support?
AB - OBJECTIVE: The aim of this study was to analyse differences in health, eating
habits and social support in adolescents with type 1 diabetes mellitus (T1DM) in
comparison to peers with another long-term illness or without any medical
condition. METHODS: We used self-reported data from the cross-sectional Health
Behaviour in School-aged Children study collected in 2014 among Slovak
adolescents as well as data from adolescents with T1DM collected in outpatient
settings (11 to 15 years old, N=8,910, 50.3% of boys). Logistic regression models
and general linear models were used to analyse differences between adolescents
with T1DM and their peers with and without long-term illness in self-rated
health, life satisfaction, health complaints, regular breakfast, sweets and soft
drink consumption, and perceived support from family, teachers and classmates.
RESULTS: Adolescents with T1DM reported worse self-rated health and suffer from
more health complaints, but they have lower chance of having breakfast
irregularly in comparison to their peers with another long-term illness or
without any medical condition. Moreover, compared with their peers, adolescents
with T1DM perceived stronger support from teachers and classmates, but weaker
support from their family. We did not confirm any differences in life
satisfaction, sweets and soft drink consumption between adolescents with T1DM and
their peers. CONCLUSIONS: Adolescents with T1DM reported more regular eating
habits, no difference in life satisfaction and more social support outside the
family in comparison to their peers. However, their worse self-rated health, more
health complaints and weaker support from family should be considered in
interventions targeting psychosocial adjustment of adolescents with T1DM.
PMID- 29346856
TI - Prevalence and Trends of Metabolic Syndrome in Slovakia during the Period of 2003
2012.
AB - OBJECTIVE: Metabolic syndrome is a combination of clinical risk factors for
cardiovascular disease as well as for diabetes. Metabolic syndrome arises from
insulin resistance accompanied with abnormal adipose deposition. The aim of our
cross-sectional time trends study was to characterize the prevalence of metabolic
syndrome and its five risk determinants among the clients of Health Advice
Centres of Regional Public Health Authorities in Slovakia. The study was
stratified by gender and age groups during the 10 year period from 2003-2012.
METHODS: Prevalence data were estimated in adults and children (>=10 years,
N=79,904) from the nationwide electronic database of Health Advice Centres of
Regional Public Health Authorities in Slovak Republic "Test of healthy heart"
from 2003 to 2012. RESULTS: The overall prevalence of metabolic syndrome was
30.2% in males and 26.6% in females, abdominal obesity was confirmed in 48.3% of
males and 53.9% of females. Increased triglyceride level has higher prevalence
among males (33.3%) compared to females (24.2%). Blood pressure (BP) values and
fasting glucose values were significantly higher in males (58.2%) than females
(41.9%). During the 10 year period from 2003 to 2012, we confirmed an increased
trend in the age-adjusted prevalence of metabolic syndrome. Abdominal obesity and
elevated triglycerides had also increased time trends prevalence in both sexes.
The prevalence of people without risk determinants of metabolic syndrome had a
time decreasing trend. A surprising finding is a decrease in the proportion of
persons with suboptimal HDL-cholesterol. The proportion of people with elevated
BP and glucose showed little change during the reporting period. CONCLUSION: The
increasing prevalence of metabolic syndrome, abdominal obesity, and elevated
triglycerides highlights the urgency of addressing these health problems as a
healthcare priority to reduce cardiovascular mortality in the Slovak Republic.
PMID- 29346857
TI - Higher Energy Intake Variability as Predisposition to Obesity: Novel Approach
Using Interquartile Range.
AB - OBJECTIVE: It is known that total energy intake and its distribution during the
day influences human anthropometric characteristics. However, possible
association between variability in total energy intake and obesity has thus far
remained unexamined. This study was designed to establish the influence of energy
intake variability of each daily meal on the anthropometric characteristics of
obesity. METHODS: A total of 521 individuals of Czech Caucasian origin aged 16-73
years (390 women and 131 men) were included in the study, 7-day food records were
completed by all study subjects and selected anthropometric characteristics were
measured. The interquartile range (IQR) of energy intake was assessed
individually for each meal of the day (as a marker of energy intake variability)
and subsequently correlated with body mass index (BMI), body fat percentage
(%BF), waist-hip ratio (WHR), and waist circumference (cW). RESULTS: Four
distinct models were created using multiple logistic regression analysis and
backward stepwise logistic regression. The most precise results, based on the
area under the curve (AUC), were observed in case of the %BF model (AUC=0.895)
and cW model (AUC=0.839). According to the %BF model, age (p<0.001) and IQR-lunch
(p<0.05) seem to play an important prediction role for obesity. Likewise,
according to the cW model, age (p<0.001), IQR-breakfast (p<0.05) and IQR-dinner
(p <0.05) predispose patients to the development of obesity. The results of our
study show that higher variability in the energy intake of key daily meals may
increase the likelihood of obesity development. CONCLUSIONS: Based on the
obtained results, it is necessary to emphasize the regularity in meals intake for
maintaining proper body composition.
PMID- 29346859
TI - Professor Vladimir Bencko Celebrates 80th Birthday.
PMID- 29346858
TI - Comprehensive Group Therapy of Obesity and Its Impact on Selected Anthropometric
and Postural Parameters.
AB - OBJECTIVE: Obesity is a multifactorial disease. This non-infectious epidemic has
reached pandemic proportions in the 21 century. Posture is a dynamic process
referring to an active maintenance of body movement segments against the action
of external forces. The aim of the study was to investigate the effect of
comprehensive group therapy for obese persons on selected anthropometric and
postural parameters. METHODS: The study comprised 53 females with a mean age of
44.5 years (range 29-65 years, standard deviation 9.42 years, median 44 years),
who completed a controlled weight loss programme. At the beginning and at the end
of the programme, anthropometric parameters (Body Mass Index (BMI), weight and
waist circumference) were measured and the posturography tests Limits of
Stability (LOS) and Motor Control Test (MCT) were performed using the NeuroCom's
SMART EquiTest system. The data were statistically analyzed using R software at a
level of significance of 0.05. RESULTS: There were positive changes after the
controlled weight loss programme in anthropometric parameters (BMI reduction,
with p<0.001; waist circumference reduction, with p<0.001; and weight loss, with
p<0.001), postural stability with statistically significant (p<0.05) improvements
in both postural activity (LOS test parameters) and reactions (MCT parameters).
CONCLUSION: The study showed a statistically significant effect of comprehensive
group therapy for obesity in terms of reductions in waist circumference, body
weight and BMI, and thus the overall reduction of both cardiovascular and
metabolic risks, as well as improved postural skills (activity and reactions).
PMID- 29346860
TI - Phase transitions between different spin-glass phases and between different
chaoses in quenched random chiral systems.
AB - The left-right chiral and ferromagnetic-antiferromagnetic double-spin-glass clock
model, with the crucially even number of states q=4 and in three dimensions d=3,
has been studied by renormalization-group theory. We find, for the first time to
our knowledge, four spin-glass phases, including conventional, chiral, and
quadrupolar spin-glass phases, and phase transitions between spin-glass phases.
The chaoses, in the different spin-glass phases and in the phase transitions of
the spin-glass phases with the other spin-glass phases, with the non-spin-glass
ordered phases, and with the disordered phase, are determined and quantified by
Lyapunov exponents. It is seen that the chiral spin-glass phase is the most
chaotic spin-glass phase. The calculated phase diagram is also otherwise very
rich, including regular and temperature-inverted devil's staircases and
reentrances.
PMID- 29346861
TI - Power series expansions for the planar monomer-dimer problem.
AB - We compute the free energy of the planar monomer-dimer model. Unlike the
classical planar dimer model, an exact solution is not known in this case. Even
the computation of the low-density power series expansion requires heavy and
nontrivial computations. Despite the exponential computational complexity, we
compute almost three times more terms than were previously known. Such an
expansion provides both lower and upper bounds for the free energy and makes it
possible to obtain more accurate numerical values than previously possible. We
expect that our methods can be applied to other similar problems.
PMID- 29346862
TI - Craters produced by explosions in a granular medium.
AB - We report on an experimental investigation of craters generated by explosions at
the surface of a model granular bed. Following the initial blast, a pressure wave
propagates through the bed, producing high-speed ejecta of grains and ultimately
a crater. We analyzed the crater morphology in the context of large-scale
explosions and other cratering processes. The process was analyzed in the context
of large-scale explosions, and the crater morphology was compared with those
resulting from other cratering processes in the same energy range. From this
comparison, we deduce that craters formed through different mechanisms can
exhibit fine surface features depending on their origin, at least at the
laboratory scale. Moreover, unlike laboratory-scale craters produced by the
impact of dense spheres, the diameter and depth do not follow a 1/4-power-law
scaling with energy, rather the exponent observed herein is approximately 0.30,
as has also been found in large-scale events. Regarding the ejecta curtain of
grains, its expansion obeys the same time dependence followed by shock waves
produced by underground explosions. Finally, from experiments in a two
dimensional system, the early cavity growth is analyzed and compared to a recent
study on explosions at the surface of water.
PMID- 29346863
TI - Nucleation of twisted and tubular states in chiral ribbons.
AB - Bilayers of chiral molecules can self-assemble into twisted and tubular
structures, as was recently shown with chiral molecular constituents such as
ssDNA-amphiphiles. I show that the dynamics of the transition between these
topologies is driven by a nucleation mechanism that bears a striking formal
similarity to that encountered in first-order wetting and dewetting transitions.
Exploiting this analogy enables the critical nuclei of the transition to be
calculated.
PMID- 29346864
TI - Effects of particle-fluid density ratio on the interactions between the turbulent
channel flow and finite-size particles.
AB - A parallel direct-forcing fictitious domain method is employed to perform fully
resolved numerical simulations of turbulent channel flow laden with finite-size
particles. The effects of the particle-fluid density ratio on the turbulence
modulation in the channel flow are investigated at the friction Reynolds number
of 180, the particle volume fraction of 0.84%, and the particle-fluid density
ratio ranging from 1 to 104.2. The results show that the variation of the flow
drag with the particle-fluid density ratio is not monotonic, with a larger flow
drag for the density ratio of 10.42, compared to those of unity and 104.2. A
significant drag reduction by the particles is observed for large particle-fluid
density ratios during the transient stage, but not at the statistically
stationary stage. The intensity of particle velocity fluctuations generally
decreases with increasing particle inertia, except that the particle streamwise
root-mean-square velocity and streamwise-transverse velocity correlation in the
near-wall region are largest at the density ratio of the order of 10. The
averaged momentum equations are derived with the spatial averaging theorem and
are used to analyze the mechanisms for the effects of the particles on the flow
drag. The results indicate that the drag-reduction effect due to the decrease in
the fluid Reynolds shear stress is counteracted by the drag-enhancement effect
due to the increase in the total particle stress or the interphase drag force for
the large particle-inertia case. The sum of the total Reynolds stress and
particle inner stress contributions to the flow drag is largest at the density
ratio of the order of 10, which is the reason for the largest flow drag at this
density ratio. The interphase drag force obtained from the averaged momentum
equation (the balance theory) is significantly smaller than (but agrees
qualitatively with) that from the empirical drag formula based on the phase
averaged slip velocity for large density ratios. For the neutrally buoyant case,
the balance theory predicts a positive interphase force on the particles arising
from the negative gradient of the particle inner stress, which cannot be
predicted by the drag formula based on the phase-averaged slip velocity. In
addition, our results show that both particle collision and particle-turbulence
interaction play roles in the formation of the inhomogeneous distribution of the
particles at the density ratio of the order of 10.
PMID- 29346865
TI - Simplification of Markov chains with infinite state space and the mathematical
theory of random gene expression bursts.
AB - Here we develop an effective approach to simplify two-time-scale Markov chains
with infinite state spaces by removal of states with fast leaving rates, which
improves the simplification method of finite Markov chains. We introduce the
concept of fast transition paths and show that the effective transitions of the
reduced chain can be represented as the superposition of the direct transitions
and the indirect transitions via all the fast transition paths. Furthermore, we
apply our simplification approach to the standard Markov model of single-cell
stochastic gene expression and provide a mathematical theory of random gene
expression bursts. We give the precise mathematical conditions for the bursting
kinetics of both mRNAs and proteins. It turns out that random bursts exactly
correspond to the fast transition paths of the Markov model. This helps us gain a
better understanding of the physics behind the bursting kinetics as an emergent
behavior from the fundamental multiscale biochemical reaction kinetics of
stochastic gene expression.
PMID- 29346866
TI - Filter method without boundary-value condition for simultaneous calculation of
eigenfunction and eigenvalue of a stationary Schrodinger equation on a grid.
AB - The paper presents a method for simultaneous computation of eigenfunction and
eigenvalue of the stationary Schrodinger equation on a grid, without imposing
boundary-value condition. The method is based on the filter operator, which
selects the eigenfunction from wave packet at the rate comparable to delta
function. The efficacy and reliability of the method are demonstrated by
comparing the simulation results with analytical or numerical solutions obtained
by using other methods for various boundary-value conditions. It is found that
the method is robust, accurate, and reliable. Further prospect of filter method
for simulation of the Schrodinger equation in higher-dimensional space will also
be highlighted.
PMID- 29346867
TI - Two distinct bifurcation routes for delayed optoelectronic oscillators.
AB - We investigate the coexistence of low- and high-frequency oscillations in a
delayed optoelectronic oscillator. We identify two nearby Hopf bifurcation points
exhibiting low and high frequencies and demonstrate analytically how they lead to
stable solutions. We then show numerically that these two branches of solutions
undergo higher order instabilities as the feedback rate is increased but remain
separated in the bifurcation diagram. The two bifurcation routes can be followed
independently by either progressively increasing or decreasing the bifurcation
parameter.
PMID- 29346868
TI - Effective one-dimensional approach to the source reconstruction problem of three
dimensional inverse optoacoustics.
AB - The direct problem of optoacoustic signal generation in biological media consists
of solving an inhomogeneous three-dimensional (3D) wave equation for an initial
acoustic stress profile. In contrast, the more defiant inverse problem requires
the reconstruction of the initial stress profile from a proper set of observed
signals. In this article, we consider an effectively 1D approach, based on the
assumption of a Gaussian transverse irradiation source profile and plane acoustic
waves, in which the effects of acoustic diffraction are described in terms of a
linear integral equation. The respective inverse problem along the beam axis can
be cast into a Volterra integral equation of the second kind for which we explore
here efficient numerical schemes in order to reconstruct initial stress profiles
from observed signals, constituting a methodical progress of computational
aspects of optoacoustics. In this regard, we explore the validity as well as the
limits of the inversion scheme via numerical experiments, with parameters geared
toward actual optoacoustic problem instances. The considered inversion input
consists of synthetic data, obtained in terms of the effectively 1D approach,
and, more generally, a solution of the 3D optoacoustic wave equation. Finally, we
also analyze the effect of noise and different detector-to-sample distances on
the optoacoustic signal and the reconstructed pressure profiles.
PMID- 29346869
TI - Brownian systems with spatially inhomogeneous activity.
AB - We generalize the Green-Kubo approach, previously applied to bulk systems of
spherically symmetric active particles [J. Chem. Phys. 145, 161101
(2016)JCPSA60021-960610.1063/1.4966153], to include spatially inhomogeneous
activity. The method is applied to predict the spatial dependence of the average
orientation per particle and the density. The average orientation is given by an
integral over the self part of the Van Hove function and a simple Gaussian
approximation to this quantity yields an accurate analytical expression. Taking
this analytical result as input to a dynamic density functional theory
approximates the spatial dependence of the density in good agreement with
simulation data. All theoretical predictions are validated using Brownian
dynamics simulations.
PMID- 29346870
TI - Nucleation and superstabilization in small systems.
AB - Phase transitions are known to present peculiarities in small systems that are
related to depletion effects of the ambient phase. Mass conservation affects the
conditions of thermodynamic equilibrium between a nucleus of the new phase and
the matrix as compared with nucleation in infinite systems. This finite-size
effect is known to delay the phase transition but can also impede nucleation in
very small systems as it stabilizes the initial state, originally metastable in
infinite systems. In this work, we investigate this superstabilization effect in
the context of classical nucleation theory in multicomponent solutions and we
derive an analytical expression for the system size below which nucleation
becomes thermodynamically impossible. Comparing with the exact solution, our
simple result is shown to accurately predict the superstabilization effect, and
can therefore be used, for instance, as a guideline for the design of novel
nanomaterials.
PMID- 29346871
TI - Electric-field-induced stretching of surface-tethered polyelectrolytes in a
microchannel.
AB - We study the stretching of a surface-tethered polyelectrolyte confined between
parallel surfaces under the application of a dc electric field. We explore the
influence of the electric-field strength, the length of the polyelectrolyte, and
the degree of confinement on the conformation of the polyelectrolyte by single
molecule experiments and coarse-grained coupled lattice-Boltzmann molecular
dynamics simulations. The fractional extension of the polyelectrolyte is found to
be a universal function of the product of the applied electric field and the
molecular contour length, which is explained by simple scaling arguments. The
degree of confinement does not have any significant influence on the stretching.
We also confirm that an electrohydrodynamic equivalence principle relating the
stretching in an electric field to that in a flow field is applicable.
PMID- 29346872
TI - Border-crossing model for the diffusive coarsening of two-dimensional and quasi
two-dimensional wet foams.
AB - For dry foams, the transport of gas from small high-pressure bubbles to large low
pressure bubbles is dominated by diffusion across the thin soap films separating
neighboring bubbles. For wetter foams, the film areas become smaller as the
Plateau borders and vertices inflate with liquid. So-called "border-blocking"
models can explain some features of wet-foam coarsening based on the presumption
that the inflated borders totally block the gas flux; however, this approximation
dramatically fails in the wet or unjamming limit where the bubbles become close
packed spheres and coarsening proceeds even though there are no films. Here, we
account for the ever-present border-crossing flux by a new length scale defined
by the average gradient of gas concentration inside the borders. We compute that
it is proportional to the geometric average of film and border thicknesses, and
we verify this scaling by numerical solution of the diffusion equation. We
similarly consider transport across inflated vertices and surface Plateau borders
in quasi-two-dimensional foams. And we show how the dA/dt=K_{0}(n-6) von Neumann
law is modified by the appearance of terms that depend on bubble size and shape
as well as the concentration gradient length scales. Finally, we use the modified
von Neumann law to compute the growth rate of the average bubble area, which is
not constant.
PMID- 29346873
TI - Autonomously responsive pumping by a bacterial flagellar forest: A mean-field
approach.
AB - This study is motivated by a microfluidic device that imparts a magnetic torque
on an array of bacterial flagella. Bacterial flagella can transform their helical
geometry autonomously in response to properties of the background fluid, which
provides an intriguing mechanism allowing their use as an engineered element for
the regulation or transport of chemicals in microscale applications. The
synchronization of flagellar phase has been widely studied in biological
contexts, but here we examine the synchronization of flagellar tilt, which is
necessary for effective pumping. We first examine the effects of helical geometry
and tilt on the pumping flows generated by a single rotating flagellum. Next, we
explore a mean-field model for an array of helical flagella to understand how
collective tilt arises and influences pumping. The mean-field methodology allows
us to take into account possible phase differences through a time-averaging
procedure and to model an infinite array of flagella. We find array separation
distances, magnetic field strengths, and rotation frequencies that produce
nontrivial self-consistent pumping solutions. For individual flagella, pumping is
reversed when helicity or rotation is reversed; in contrast, when collective
effects are included, self-consistent tilted pumping solutions become untilted
nonpumping solutions when helicity or rotation is reversed.
PMID- 29346874
TI - Internal autoresonance in coupled oscillators with slowly decaying frequency.
AB - In this work, we study resonance energy transfer from an impulsively loaded
strongly nonlinear oscillator to a weakly coupled linear attachment with a slowly
time-decaying stiffness. It is shown that even in the absence of external
periodic forcing both oscillators may exhibit the resonance phenomenon, with the
permanent response enhancement of the linear oscillator and the corresponding
response reduction of the nonlinear actuator. This effect is said to be internal
autoresonance. The influence of the system parameters on the emergence and
stability of autoresonance is investigated both analytically and numerically.
PMID- 29346875
TI - Granular temperature measured experimentally in a shear flow by acoustic energy.
AB - Granular temperature may control high-speed granular flows, yet it is difficult
to measure in laboratory experiments. Here we utilize acoustic energy to measure
granular temperature in dense shear flows. We show that acoustic energy captures
the anticipated behavior of granular temperature as a function of grain size in
quartz sand shear flows. We also find that granular temperature (through its
proxy acoustic energy) is nearly linearly proportional to inertial number, and
dilation is proportional to acoustic energy raised to the power 0.6+/-0.2. This
demonstrates the existence of a relationship between granular temperature and
dilation. It is also consistent with previous results on dilation due to
externally imposed vibration, thus showing that internally and externally induced
vibrations have identical results on granular shear flows.
PMID- 29346876
TI - X-ray scattering reveals molecular tilt is an order parameter for the main phase
transition in a model biomembrane.
AB - Synchrotron diffuse x-ray scattering data reveal a dramatic softening of the
molecular tilt modulus K_{theta} of the model biomembrane composed of DMPC lipids
as the temperature is lowered towards the main phase transition temperature at
T_{M}=24^{?}C. Spontaneous tilt occurs below T_{M}, suggesting that tilt is a
symmetry breaking order parameter. Consistent with this hypothesis, it is also
found that a different lipid POPS has no spontaneous tilt below its T_{M} at
14^{?}C and correspondingly its tilt modulus did not soften as T_{M} was
approached from above. As previously known, the bending modulus K_{C} of DMPC
also softens close to T_{M}, but unlike the tilt modulus, K_{C} has a maximum
3^{?} above T_{M}, which also marks the limit of the well-known anomalous
swelling regime. Tilt adds a different perspective to our previous understanding
of the main phase transition in lipid bilayers.
PMID- 29346877
TI - Stable three-dimensional modon soliton in plasmas.
AB - We derive the nonlinear equations that describe coupled drift waves and ion
acoustic waves in a plasma. We show that when the coupling to ion acoustic waves
is negligible, the reduced nonlinear equation is a generalization of the Hasegawa
Mima equation to the three-dimensional (3D) case. We find an exact analytical
solution of this equation in the form of a 3D soliton drift wave (3D modon). By
numerical simulations we study collisions between the modons and show that the
collisions can be fully elastic.
PMID- 29346878
TI - Publisher's Note: Golf-course and funnel energy landscapes: Protein folding
concepts in martensites [Phys. Rev. E 95, 063003 (2017)].
AB - This corrects the article DOI: 10.1103/PhysRevE.95.063003.
PMID- 29346879
TI - Phase behavior of binary and polydisperse suspensions of compressible microgels
controlled by selective particle deswelling.
AB - We investigate the phase behavior of suspensions of poly(N-isopropylacrylamide)
(pNIPAM) microgels with either bimodal or polydisperse size distribution. We
observe a shift of the fluid-crystal transition to higher concentrations
depending on the polydispersity or the fraction of large particles in suspension.
Crystallization is observed up to polydispersities as high as 18.5%, and up to a
number fraction of large particles of 29% in bidisperse suspensions. The crystal
structure is random hexagonal close-packed as in monodisperse pNIPAM microgel
suspensions. We explain our experimental results by considering the effect of
bound counterions. Above a critical particle concentration, these cause
deswelling of the largest microgels, which are the softest, changing the size
distribution of the suspension and enabling crystal formation in conditions where
incompressible particles would not crystallize.
PMID- 29346880
TI - Emergence and detailed structure of terraced surfaces produced by oblique
incidence ion sputtering.
AB - We study the nanoscale terraced topographies that arise when a solid surface is
bombarded with a broad ion beam that has a relatively high angle of incidence
theta. We find that the surface is not completely flat between the regions in
which the surface slope changes rapidly with position: Instead, small-amplitude
ripples propagate along the surface. Our analytical work on these ripples yields
their propagation velocity as well as the scaling behavior of their amplitude.
Our simulations establish that the surfaces exhibit interrupted coarsening, i.e.,
the characteristic width and height of the surface disturbance grow for a time
but ultimately asymptote to finite values as the fully terraced state develops.
In addition, as theta is reduced, the surface can undergo a transition from a
terraced morphology that changes little with time as it propagates over the
surface to an unterraced state that appears to exhibit spatiotemporal chaos. For
different ranges of the parameters, our equation of motion produces unterraced
topographies that are remarkably similar to those seen in various experiments,
including pyramidal structures that are elongated along the projected beam
direction and isolated lenticular depressions.
PMID- 29346881
TI - Coda reconstruction from cross-correlation of a diffuse field on thin elastic
plates.
AB - This study contributes to the evaluation of the robustness and accuracy of
Green's function reconstruction from cross-correlation of strongly dispersed
reverberated signals, with disentangling of the respective roles of ballistic and
reverberated ("coda") contributions. We conduct a suite of experiments on a
highly reverberating thin duralumin plate, where an approximately diffuse
flexural wave field is generated by taking advantage of the plate reverberation
and wave dispersion. A large number of impulsive sources that cover the whole
surface of the plate are used to validate ambient-noise theory through comparison
of the causal and anticausal (i.e., positive- and negative-time) terms of the
cross-correlation to one another and to the directly measured Green's function.
To quantify the contribution of the ballistic and coda signals, the cross
correlation integral is defined over different time windows of variable length,
and the accuracy of the reconstructed Green's function is studied as a function
of the initial and end times of the integral. We show that even cross
correlations measured over limited time windows converge to a significant part of
the Green's function. Convergence is achieved over a wide time window, which
includes not only direct flexural-wave arrivals, but also the multiply
reverberated coda. We propose a model, based on normal-mode analysis, that
relates the similarity between the cross-correlation and the Green's function to
the statistical properties of the plate. We also determine quantitatively how
incoherent noise degrades the estimation of the Green's function.
PMID- 29346882
TI - Morphological-evolution pathway during phase separation in polymer solutions with
highly asymmetrical miscibility gap.
AB - Microstructural evolution during thermally induced phase separation in a polymer
solution with a highly asymmetrical miscibility gap is analyzed using Flory
Huggins thermodynamics and nonlinear Cahn-Hilliard kinetics. Computer simulation
results demonstrate that, in contrast to systems with symmetric miscibility gaps,
interesting morphological-evolution pathways (MEPs) including cluster-to
percolation and percolation-to-cluster transitions are identified. These MEPs are
rationalized according to asynchronous evolution of the two product phases. For a
highly asymmetric polymer system, the initial solution composition is also found
to play a critical role in determining the MEPs. According to the simulation
results a map of MEPs in terms of initial solution composition and aging time of
phase separation is established to guide future microstructural design in
asymmetrical polymer solutions.
PMID- 29346883
TI - Force spectroscopy unravels the role of ionic strength on DNA-cisplatin
interaction: Modulating the binding parameters.
AB - In the present work we have gone a step forward in the understanding of the DNA
cisplatin interaction, investigating the role of the ionic strength on the
complexes formation. To achieve this task, we use optical tweezers to perform
force spectroscopy on the DNA-cisplatin complexes, determining their mechanical
parameters as a function of the drug concentration in the sample for three
different buffers. From such measurements, we determine the binding parameters
and study their behavior as a function of the ionic strength. The equilibrium
binding constant decreases with the counterion concentration ([Na]) and can be
used to estimate the effective net charge of cisplatin in solution. The
cooperativity degree of the binding reaction, on the other hand, increases with
the ionic strength, as a result of the different conformational changes induced
by the drug on the double-helix when binding under different buffer conditions.
Such results can be used to modulate the drug binding to DNA, by appropriately
setting the ionic strength of the surrounding buffer. The conclusions drawn
provide significant new insights on the complex cooperative interactions between
the DNA molecule and the class of platinum-based compounds, much used in
chemotherapies.
PMID- 29346884
TI - Nonstationary dynamics of encounters: Mean valuable territory covered by a random
searcher.
AB - Inspired by recent experiments on the organism Caenorhabditis elegans we present
a stochastic problem to capture the adaptive dynamics of search in living beings,
which involves the exploration-exploitation dilemma between remaining in a
previously preferred area and relocating to new places. We assess the question of
search efficiency by introducing a new magnitude, the mean valuable territory
covered by a Browinan searcher, for the case where each site in the domain
becomes valuable only after a random time controlled by a nonhomogeneous rate
which expands from the origin outwards. We explore analytically this magnitude
for domains of dimensions 1, 2, and 3 and discuss the theoretical and applied
(biological) interest of our approach. As the main results here, we (i) report
the existence of some universal scaling properties for the mean valuable
territory covered as a function of time and (ii) reveal the emergence of an
optimal diffusivity which appears only for domains in two and higher dimensions.
PMID- 29346885
TI - Theoretical microbial ecology without species.
AB - Ecosystems are commonly conceptualized as networks of interacting species.
However, partitioning natural diversity of organisms into discrete units is
notoriously problematic and mounting experimental evidence raises the intriguing
question whether this perspective is appropriate for the microbial world. Here an
alternative formalism is proposed that does not require postulating the existence
of species as fundamental ecological variables and provides a naturally
hierarchical description of community dynamics. This formalism allows approaching
the species problem from the opposite direction. While the classical models treat
a world of imperfectly clustered organism types as a perturbation around well
clustered species, the presented approach allows gradually adding structure to a
fully disordered background. The relevance of this theoretical construct for
describing highly diverse natural ecosystems is discussed.
PMID- 29346886
TI - Predictability of escape for a stochastic saddle-node bifurcation: When rare
events are typical.
AB - Transitions between multiple stable states of nonlinear systems are ubiquitous in
physics, chemistry, and beyond. Two types of behaviors are usually seen as
mutually exclusive: unpredictable noise-induced transitions and predictable
bifurcations of the underlying vector field. Here, we report a different
situation, corresponding to a fluctuating system approaching a bifurcation, where
both effects collaborate. We show that the problem can be reduced to a single
control parameter governing the competition between deterministic and stochastic
effects. Two asymptotic regimes are identified: When the control parameter is
small (e.g., small noise), deviations from the deterministic case are well
described by the Freidlin-Wentzell theory. In particular, escapes over the
potential barrier are very rare events. When the parameter is large (e.g., large
noise), such events become typical. Unlike pure noise-induced transitions, the
distribution of the escape time is peaked around a value which is asymptotically
predicted by an adiabatic approximation. We show that the two regimes are
characterized by qualitatively different reacting trajectories with algebraic and
exponential divergences, respectively.
PMID- 29346887
TI - Time correlation functions in the Lebwohl-Lasher model of liquid crystals.
AB - Time correlation functions in the Lebwohl-Lasher model of nematic liquid crystals
are studied using theory and molecular dynamics simulations. In particular, the
autocorrelation functions of angular momentum and nematic director fluctuations
are calculated in the long-wavelength limit. The constitutive relations for the
hydrodynamic currents are derived using a standard procedure based on non
negativity of the entropy production. The continuity equations are then
linearized and solved to calculate the correlation functions. We find that the
transverse angular momentum fluctuations are coupled to the director fluctuations
and are both propagative. The propagative nature of the fluctuations suppresses
the anticipated hydrodynamic long-time tails in the single-particle
autocorrelation functions. The fluctuations in the isotropic phase are, however,
diffusive, leading to t^{-d/2} long-time tails in d spatial dimensions. The Frank
elastic constant measured using the time correlation functions are in good
agreement with previously reported results.
PMID- 29346888
TI - Critical adsorption profiles around a sphere and a cylinder in a fluid at
criticality: Local functional theory.
AB - We study universal critical adsorption on a solid sphere and a solid cylinder in
a fluid at bulk criticality, where preferential adsorption occurs. We use a local
functional theory proposed by Fisher et al. [M. E. Fisher and P. G. de Gennes, C.
R. Acad. Sci. Paris Ser. B 287, 207 (1978); M. E. Fisher and H. Au-Yang, Physica
A 101, 255 (1980)PHYADX0378-437110.1016/0378-4371(80)90112-0]. We calculate the
mean order parameter profile psi(r), where r is the distance from the sphere
center and the cylinder axis, respectively. The resultant differential equation
for psi(r) is solved exactly around a sphere and numerically around a cylinder. A
strong adsorption regime is realized except for very small surface field h_{1},
where the surface order parameter psi(a) is determined by h_{1} and is
independent of the radius a. If r considerably exceeds a, psi(r) decays as r^{
(1+eta)} for a sphere and r^{-(1+eta)/2} for a cylinder in three dimensions,
where eta is the critical exponent in the order parameter correlation at bulk
criticality.
PMID- 29346889
TI - Morphological inversion of complex diffusion.
AB - Epidemics, neural cascades, power failures, and many other phenomena can be
described by a diffusion process on a network. To identify the causal origins of
a spread, it is often necessary to identify the triggering initial node. Here, we
define a new morphological operator and use it to detect the origin of a
diffusive front, given the final state of a complex network. Our method performs
better than algorithms based on distance (closeness) and Jordan centrality. More
importantly, our method is applicable regardless of the specifics of the forward
model, and therefore can be applied to a wide range of systems such as
identifying the patient zero in an epidemic, pinpointing the neuron that triggers
a cascade, identifying the original malfunction that causes a catastrophic
infrastructure failure, and inferring the ancestral species from which a
heterogeneous population evolves.
PMID- 29346890
TI - Mechanics of active surfaces.
AB - We derive a fully covariant theory of the mechanics of active surfaces. This
theory provides a framework for the study of active biological or chemical
processes at surfaces, such as the cell cortex, the mechanics of epithelial
tissues, or reconstituted active systems on surfaces. We introduce forces and
torques acting on a surface, and derive the associated force balance conditions.
We show that surfaces with in-plane rotational symmetry can have broken up-down,
chiral, or planar-chiral symmetry. We discuss the rate of entropy production in
the surface and write linear constitutive relations that satisfy the Onsager
relations. We show that the bending modulus, the spontaneous curvature, and the
surface tension of a passive surface are renormalized by active terms. Finally,
we identify active terms which are not found in a passive theory and discuss
examples of shape instabilities that are related to active processes in the
surface.
PMID- 29346891
TI - Discrete-to-continuum modeling of weakly interacting incommensurate chains.
AB - In this paper we use a formal discrete-to-continuum procedure to derive a
continuum variational model for two chains of atoms with slightly incommensurate
lattices. The chains represent a cross section of a three-dimensional system
consisting of a graphene sheet suspended over a substrate. The continuum model
recovers both qualitatively and quantitatively the behavior observed in the
corresponding discrete model. The numerical solutions for both models demonstrate
the presence of large commensurate regions separated by localized incommensurate
domain walls.
PMID- 29346892
TI - Anomalous stress fluctuations in athermal two-dimensional amorphous solids.
AB - We numerically study the local stress distribution within athermal, isotropically
stressed, mechanically stable, packings of bidisperse frictionless disks above
the jamming transition in two dimensions. Considering the Fourier transform of
the local stress, we find evidence for algebraically increasing fluctuations in
both isotropic and anisotropic components of the stress tensor at small wave
numbers, contrary to recent theoretical predictions. Such increasing fluctuations
imply a lack of self-averaging of the stress on large length scales. The
crossover to these increasing fluctuations defines a length scale l_{0}, however,
it appears that l_{0} does not vary much with packing fraction phi, nor does
l_{0} seem to be diverging as phi approaches the jamming phi_{J}. We also find
similar large length scale fluctuations of stress in the inherent states of a
quenched Lennard-Jones liquid, leading us to speculate that such fluctuations may
be a general property of amorphous solids in two dimensions.
PMID- 29346893
TI - Resuspension threshold of a granular bed by localized heating.
AB - The resuspension and dispersion of particles occur in industrial fluid dynamic
processes as well as environmental and geophysical situations. In this paper, we
experimentally investigate the ability to fluidize a granular bed with a vertical
gradient of temperature. Using laboratory experiments with a localized heat
source, we observe a large entrainment of particles into the fluid volume beyond
a threshold temperature. The buoyancy-driven fluidized bed then leads to the
transport of solid particles through the generation of particle-laden plumes. We
show that the destabilization process is driven by the thermal conductivity
inside the granular bed and demonstrate that the threshold temperature depends on
the thickness of the granular bed and the buoyancy number, i.e., the ratio of the
stabilizing density contrast to the destabilizing thermal density contrast.
PMID- 29346894
TI - Size scaling of failure strength with fat-tailed disorder in a fiber bundle
model.
AB - We investigate the size scaling of the macroscopic fracture strength of
heterogeneous materials when microscopic disorder is controlled by fat-tailed
distributions. We consider a fiber bundle model where the strength of single
fibers is described by a power law distribution over a finite range. Tuning the
amount of disorder by varying the power law exponent and the upper cutoff of
fibers' strength, in the limit of equal load sharing an astonishing size effect
is revealed: For small system sizes the bundle strength increases with the number
of fibers, and the usual decreasing size effect of heterogeneous materials is
restored only beyond a characteristic size. We show analytically that the extreme
order statistics of fibers' strength is responsible for this peculiar behavior.
Analyzing the results of computer simulations we deduce a scaling form which
describes the dependence of the macroscopic strength of fiber bundles on the
parameters of microscopic disorder over the entire range of system sizes.
PMID- 29346895
TI - Levy walks in nonhomogeneous environments.
AB - The Levy walk process with rests is discussed. The jumping time is governed by an
alpha-stable distribution with alpha>1 while a waiting time distribution is
Poissonian and involves a position-dependent rate which reflects a nonhomogeneous
trap distribution. The master equation is derived and solved in the asymptotic
limit for a power-law form of the jumping rate. The relative density of resting
and flying particles appears time-dependent, and the asymptotic form of both
distributions obeys a stretched-exponential shape at large time. The diffusion
properties are discussed, and it is demonstrated that, due to the heterogeneous
trap structure, the enhanced diffusion, observed for the homogeneous case, may
turn to a subdiffusion. The density distributions and mean squared displacements
are also evaluated from Monte Carlo simulations of individual trajectories.
PMID- 29346896
TI - Nonequilibrium thermodynamics with binary quantum correlations.
AB - The balance equations for thermodynamic quantities are derived from the nonlocal
quantum kinetic equation. The nonlocal collisions lead to molecular contributions
to the observables and currents. The corresponding correlated parts of the
observables are found to be given by the rate to form a molecule multiplied with
its lifetime which can be considered as collision duration. Explicit expressions
of these molecular contributions are given in terms of the scattering phase
shifts. The two-particle form of the entropy is derived extending the Landau
quasiparticle picture by two-particle molecular contributions. There is a
continuous exchange of correlation and kinetic energies condensing into the rate
of correlated variables for energy and momentum. For the entropy, an explicit
gain remains and Boltzmann's H theorem is proved including the molecular parts of
the entropy.
PMID- 29346897
TI - Quantum Otto engine with exchange coupling in the presence of level degeneracy.
AB - We consider a quasistatic quantum Otto cycle using two effectively two-level
systems with degeneracy in the excited state. The systems are coupled through
isotropic exchange interaction of strength J>0, in the presence of an external
magnetic field B which is varied during the cycle. We prove the positive work
condition and show that level degeneracy can act as a thermodynamic resource, so
that a larger amount of work can be extracted than in the nondegenerate case,
both with and without coupling. We also derive an upper bound for the efficiency
of the cycle. This bound is the same as derived for a system of coupled spin-1/2
particles [G. Thomas and R. S. Johal, Phys. Rev. E 83, 031135 (2011)PLEEE81539
375510.1103/PhysRevE.83.031135], i.e., without degeneracy, and depends only on
the control parameters of the Hamiltonian, being independent of the level
degeneracy and the reservoir temperatures.
PMID- 29346898
TI - Stochastic Kuramoto oscillators with discrete phase states.
AB - We present a generalization of the Kuramoto phase oscillator model in which
phases advance in discrete phase increments through Poisson processes, rendering
both intrinsic oscillations and coupling inherently stochastic. We study the
effects of phase discretization on the synchronization and precision properties
of the coupled system both analytically and numerically. Remarkably, many key
observables such as the steady-state synchrony and the quality of oscillations
show distinct extrema while converging to the classical Kuramoto model in the
limit of a continuous phase. The phase-discretized model provides a general
framework for coupled oscillations in a Markov chain setting.
PMID- 29346899
TI - Formation and relaxation of quasistationary states in particle systems with power
law interactions.
AB - We explore the formation and relaxation of the so-called quasistationary states
(QSS) for particle distributions in three dimensions interacting via an
attractive radial pair potential V(r->infinity)~1/r^{gamma} with gamma>0, and
either a soft core or hard core regularization at small r. In the first part of
the paper, we generalize, for any spatial dimension d>=2, Chandrasekhar's
approach for the case of gravity to obtain analytic estimates of the rate of
collisional relaxation due to two-body collisions. The resultant relaxation rates
indicate an essential qualitative difference depending on the integrability of
the pair force at large distances: for gamma>d-1, the rate diverges in the large
particle number N (mean-field) limit, unless a sufficiently large soft core is
present; for gamma=d-1, the
existence of such states will be conditioned strongly on the short-range
properties of the interaction.
PMID- 29346900
TI - Smoothed particle hydrodynamics study of the roughness effect on contact angle
and droplet flow.
AB - We employ a pairwise force smoothed particle hydrodynamics (PF-SPH) model to
simulate sessile and transient droplets on rough hydrophobic and hydrophilic
surfaces. PF-SPH allows modeling of free-surface flows without discretizing the
air phase, which is achieved by imposing the surface tension and dynamic contact
angles with pairwise interaction forces. We use the PF-SPH model to study the
effect of surface roughness and microscopic contact angle on the effective
contact angle and droplet dynamics. In the first part of this work, we
investigate static contact angles of sessile droplets on different types of rough
surfaces. We find that the effective static contact angles of Cassie and Wenzel
droplets on a rough surface are greater than the corresponding microscale static
contact angles. As a result, microscale hydrophobic rough surfaces also show
effective hydrophobic behavior. On the other hand, microscale hydrophilic
surfaces may be macroscopically hydrophilic or hydrophobic, depending on the type
of roughness. We study the dependence of the transition between Cassie and Wenzel
states on roughness and droplet size, which can be linked to the critical
pressure for the given fluid-substrate combination. We observe good agreement
between simulations and theoretical predictions. Finally, we study the impact of
the roughness orientation (i.e., an anisotropic roughness) and surface
inclination on droplet flow velocities. Simulations show that droplet flow
velocities are lower if the surface roughness is oriented perpendicular to the
flow direction. If the predominant elements of surface roughness are in alignment
with the flow direction, the flow velocities increase compared to smooth
surfaces, which can be attributed to the decrease in fluid-solid contact area
similar to the lotus effect. We demonstrate that classical linear scaling
relationships between Bond and capillary numbers for droplet flow on flat
surfaces also hold for flow on rough surfaces.
PMID- 29346901
TI - Method of model reduction and multifidelity models for solute transport in random
layered porous media.
AB - This work presents a method of model reduction that leads to models with three
solutions of increasing fidelity (multifidelity models) for solute transport in a
bounded layered porous media with random permeability. The model generalizes the
Taylor-Aris dispersion theory to stochastic transport in random layered porous
media with a known velocity covariance function. In the reduced model, we
represent (random) concentration in terms of its cross-sectional average and a
variation function. We derive a one-dimensional stochastic advection-dispersion
type equation for the average concentration and a stochastic Poisson equation for
the variation function, as well as expressions for the effective velocity and
dispersion coefficient. In contrast to the linear scaling with the correlation
length and the mean velocity from macrodispersion theory, our model predicts a
nonlinear and a quadratic dependence of the effective dispersion on the
correlation length and the mean velocity, respectively. We observe that velocity
fluctuations enhance dispersion in a nonmonotonic fashion (a stochastic spike
phenomenon): The dispersion initially increases with correlation length lambda,
reaches a maximum, and decreases to zero at infinity (correlation). Maximum
enhancement in dispersion can be obtained at a correlation length about 0.25 the
size of the porous media perpendicular to flow. This information can be useful
for engineering such random layered porous media. Numerical simulations are
implemented to compare solutions with varying fidelity.
PMID- 29346902
TI - Transport, diffusion, and energy studies in the Arnold-Beltrami-Childress map.
AB - We study the transport and diffusion properties of passive inertial particles
described by a six-dimensional dissipative bailout embedding map. The base map
chosen for the study is the three-dimensional incompressible Arnold-Beltrami
Childress (ABC) map chosen as a representation of volume preserving flows. There
are two distinct cases: the two-action and the one-action cases, depending on
whether two or one of the parameters (A,B,C) exceed 1. The embedded map dynamics
is governed by two parameters (alpha,gamma), which quantify the mass density
ratio and dissipation, respectively. There are important differences between the
aerosol (alpha<1) and the bubble (alpha>1) regimes. We have studied the diffusive
behavior of the system and constructed the phase diagram in the parameter space
by computing the diffusion exponents eta. Three classes have been broadly
classified-subdiffusive transport (eta<1), normal diffusion (eta~1), and
superdiffusion (eta>1) with eta~2 referred to as the ballistic regime.
Correlating the diffusive phase diagram with the phase diagram for dynamical
regimes seen earlier, we find that the hyperchaotic bubble regime is largely
correlated with normal and superdiffusive behavior. In contrast, in the aerosol
regime, ballistic superdiffusion is seen in regions that largely show periodic
dynamical behaviors, whereas subdiffusive behavior is seen in both periodic and
chaotic regimes. The probability distributions of the diffusion exponents show
power-law scaling for both aerosol and bubbles in the superdiffusive regimes. We
further study the Poincare recurrence times statistics of the system. Here, we
find that recurrence time distributions show power law regimes due to the
existence of partial barriers to transport in the phase space. Moreover, the plot
of average particle kinetic energies versus the mass density ratio for the two
action case exhibits a devil's staircase-like structure for higher dissipation
values. We explain these results and discuss their implications for realistic
systems.
PMID- 29346903
TI - Pseudospectral Maxwell solvers for an accurate modeling of Doppler harmonic
generation on plasma mirrors with particle-in-cell codes.
AB - With the advent of petawatt class lasers, the very large laser intensities
attainable on target should enable the production of intense high-order Doppler
harmonics from relativistic laser-plasma mirror interactions. At present, the
modeling of these harmonics with particle-in-cell (PIC) codes is extremely
challenging as it implies an accurate description of tens to hundreds of harmonic
orders on a broad range of angles. In particular, we show here that due to the
numerical dispersion of waves they induce in vacuum, standard finite difference
time domain (FDTD) Maxwell solvers employed in most PIC codes can induce a
spurious angular deviation of harmonic beams potentially degrading simulation
results. This effect was extensively studied and a simple toy model based on the
Snell-Descartes law was developed that allows us to finely predict the angular
deviation of harmonics depending on the spatiotemporal resolution and the Maxwell
solver used in the simulations. Our model demonstrates that the mitigation of
this numerical artifact with FDTD solvers mandates very high spatiotemporal
resolution preventing realistic three-dimensional (3D) simulations even on the
largest computers available at the time of writing. We finally show that
nondispersive pseudospectral analytical time domain solvers can considerably
reduce the spatiotemporal resolution required to mitigate this spurious deviation
and should enable in the near future 3D accurate modeling on supercomputers in a
realistic time to solution.
PMID- 29346904
TI - Extracting oscillating components from nonstationary time series: A wavelet
induced method.
AB - This paper consists in the description and application of a method called wavelet
induced mode extraction (WIME) in the context of time-frequency analysis. WIME
aims to extract the oscillating components that build amplitude modulated
frequency modulated signals. The essence of this technique relies on the
successive extractions of the dominant ridges of wavelet-based time-frequency
representations of the signal under consideration. Our tests on simulated
examples indicate strong decomposition and reconstruction skills, trouble-free
handling of crossing trajectories in the time-frequency plane, sharp performances
in frequency detection in the case of mode-mixing problems, and a natural
tolerance to noise. These results are compared with those obtained with empirical
mode decomposition. We also show that WIME still gives meaningful results with
real-life data, namely, the Oceanic Nino Index.
PMID- 29346905
TI - Predicting Escherichia coli's chemotactic drift under exponential gradient.
AB - Bacterial species are known to show chemotaxis, i.e., the directed motions in the
presence of certain chemicals, whereas the motion is random in the absence of
those chemicals. The bacteria modulate their run time to induce chemotactic drift
towards the attractant chemicals and away from the repellent chemicals. However,
the existing theoretical knowledge does not exhibit a proper match with
experimental validation, and hence there is a need for developing alternate
models and validating experimentally. In this paper a more robust theoretical
model is proposed to investigate chemotactic drift of peritrichous Escherichia
coli under an exponential nutrient gradient. An exponential gradient is used to
understand the steady state behavior of drift because of the logarithmic
functionality of the chemosensory receptors. Our theoretical estimations are
validated through the experimentation and simulation results. Thus, the developed
model successfully delineates the run time, run trajectory, and drift velocity as
measured from the experiments.
PMID- 29346906
TI - Smoothed particle hydrodynamics method for evaporating multiphase flows.
AB - The smoothed particle hydrodynamics (SPH) method has been increasingly used for
simulating fluid flows; however, its ability to simulate evaporating flow
requires significant improvements. This paper proposes an SPH method for
evaporating multiphase flows. The present SPH method can simulate the heat and
mass transfers across the liquid-gas interfaces. The conservation equations of
mass, momentum, and energy were reformulated based on SPH, then were used to
govern the fluid flow and heat transfer in both the liquid and gas phases. The
continuity equation of the vapor species was employed to simulate the vapor mass
fraction in the gas phase. The vapor mass fraction at the interface was predicted
by the Clausius-Clapeyron correlation. An evaporation rate was derived to predict
the mass transfer from the liquid phase to the gas phase at the interface.
Because of the mass transfer across the liquid-gas interface, the mass of an SPH
particle was allowed to change. Alternative particle splitting and merging
techniques were developed to avoid large mass difference between SPH particles of
the same phase. The proposed method was tested by simulating three problems,
including the Stefan problem, evaporation of a static drop, and evaporation of a
drop impacting a hot surface. For the Stefan problem, the SPH results of the
evaporation rate at the interface agreed well with the analytical solution. For
drop evaporation, the SPH result was compared with the result predicted by a
level-set method from the literature. In the case of drop impact on a hot
surface, the evolution of the shape of the drop, temperature, and vapor mass
fraction were predicted.
PMID- 29346907
TI - Fast electrons generated by quasistatic electric fields of a fs-laser-pulse
induced plasma.
AB - We present a new acceleration mechanism for electrons taking place during the
interaction of an ultrashort, nonrelativistic laser pulse with a plasma generated
at the surface of a solid density target. In our experiments, the plasma is
created by a laser pulse with femtosecond duration and an energy of about 1 mJ
focused to intensities of above 10^{17}W/cm^{2}. We observe that the electron
energies acquired by this mechanism exceed the ponderomotive potential of the
laser by an order of magnitude. This result was reproduced and quantitatively
confirmed by particle-in-cell simulations, which further revealed that the
observed electron acceleration is based on quasistatic electric fields caused by
the space charges of ponderomotively preaccelerated electrons. This acceleration
process is examined in more detail by a simplified numerical model, which allows
a qualitative explanation of the final electron energies.
PMID- 29346908
TI - Mechanisms of self-organized criticality in social processes of knowledge
creation.
AB - In online social dynamics, a robust scale invariance appears as a key feature of
collaborative efforts that lead to new social value. The underlying empirical
data thus offers a unique opportunity to study the origin of self-organized
criticality (SOC) in social systems. In contrast to physical systems in the
laboratory, various human attributes of the actors play an essential role in the
process along with the contents (cognitive, emotional) of the communicated
artifacts. As a prototypical example, we consider the social endeavor of
knowledge creation via Questions and Answers (Q&A). Using a large empirical data
set from one of such Q&A sites and theoretical modeling, we reveal fundamental
characteristics of SOC by investigating the temporal correlations at all scales
and the role of cognitive contents to the avalanches of the knowledge-creation
process. Our analysis shows that the universal social dynamics with power-law
inhomogeneities of the actions and delay times provides the primary mechanism for
self-tuning towards the critical state; it leads to the long-range correlations
and the event clustering in response to the external driving by the arrival of
new users. In addition, the involved cognitive contents (systematically annotated
in the data and observed in the model) exert important constraints that identify
unique classes of the knowledge-creation avalanches. Specifically, besides
determining a fine structure of the developing knowledge networks, they affect
the values of scaling exponents and the geometry of large avalanches and shape
the multifractal spectrum. Furthermore, we find that the level of the activity of
the communities that share the knowledge correlates with the fluctuations of the
innovation rate, implying that the increase of innovation may serve as the active
principle of self-organization. To identify relevant parameters and unravel the
role of the network evolution underlying the process in the social system under
consideration, we compare the social avalanches to the avalanche sequences
occurring in the field-driven physical model of disordered solids, where the
factors contributing to the collective dynamics are better understood.
PMID- 29346909
TI - Random matrices and the New York City subway system.
AB - We analyze subway arrival times in the New York City subway system. We find
regimes where the gaps between trains are well modeled by (unitarily invariant)
random matrix statistics and Poisson statistics. The departure from random matrix
statistics is captured by the value of the Coulomb potential along the subway
route. This departure becomes more pronounced as trains make more stops.
PMID- 29346910
TI - Dynamics-dependent synchronization in on-chip coupled semiconductor lasers.
AB - Synchronization properties of chaotic dynamics in two mutually coupled
semiconductor lasers with optical feedback embedded in a photonic integrated
circuit are investigated from the point of view of their dynamical content. A
phenomenon in which the two lasers can show qualitatively different
synchronization properties according to the frequency range of investigation and
their nonlinear dynamics is identified and termed dynamics-dependent
synchronization. In-phase synchronization is observed for original signals and
antiphase synchronization is observed for low-pass filtered signals in the case
where one of the lasers shows chaotic oscillations while the other laser exhibits
low-frequency fluctuations dynamics. The experimental conditions causing the
synchronization states to vary according to the considered frequency interval are
studied and the key roles of asymmetric coupling strength and injection currents
are clarified.
PMID- 29346911
TI - Avalanche precursors in a frictional model.
AB - We present a one-dimensional numerical model based on elastically coupled sliders
on a frictional incline of variable tilt. This very simple approach makes it
possible to study the precursors to the avalanche and to provide a
rationalization of different features that have been observed in experiments. We
provide a statistical description of the model leading to master equations
describing the state of the system as a function of the angle of inclination. Our
central results are the reproduction of large-scale regular events preceding the
avalanche, on the one hand, and an analytical approach providing an internal
threshold for the outbreak of rearrangements before the avalanche in the system,
on the other hand.
PMID- 29346912
TI - Wedge wetting by electrolyte solutions.
AB - The wetting of a charged wedgelike wall by an electrolyte solution is
investigated by means of classical density functional theory. As in other studies
on wedge wetting, this geometry is considered as the most simple deviation from a
planar substrate, and it serves as a first step toward more complex confinements
of fluids. By focusing on fluids containing ions and surface charges, features of
real systems are covered that are not accessible within the vast majority of
previous theoretical studies concentrating on simple fluids in contact with
uncharged wedges. In particular, the filling transition of charged wedges is
necessarily of first order, because wetting transitions of charged substrates are
of first order and the barrier in the effective interface potential persists
below the wetting transition of a planar wall; hence, critical filling
transitions are not expected to occur for ionic systems. The dependence of the
critical opening angle on the surface charge, as well as the dependence of the
filling height, of the wedge adsorption, and of the line tension on the opening
angle and on the surface charge are analyzed in detail.
PMID- 29346913
TI - Strained-graphene-based highly efficient quantum heat engine operating at maximum
power.
AB - A strained graphene monolayer is shown to operate as a highly efficient quantum
heat engine delivering maximum power. The efficiency and power of the proposed
device exceeds that of recent proposals. The reason for these excellent
characteristics is that strain enables complete valley separation in
transmittance through the device, implying that increasing strain leads to very
high Seebeck coefficient as well as lower conductance. In addition, since time
reversal symmetry is unbroken in our system, the proposed strained graphene
quantum heat engine can also act as a high-performance refrigerator.
PMID- 29346914
TI - Noise-induced torus bursting in the stochastic Hindmarsh-Rose neuron model.
AB - We study the phenomenon of noise-induced torus bursting on the base of the three
dimensional Hindmarsh-Rose neuron model forced by additive noise. We show that in
the parametric zone close to the Neimark-Sacker bifurcation, where the
deterministic system exhibits rapid tonic spiking oscillations, random
disturbances can turn tonic spiking into bursting, which is characterized by the
formation of a peculiar dynamical structure resembling that of a torus. This
phenomenon is confirmed by the changes in dispersion of random trajectories as
well as the power spectral density and interspike intervals statistics. In
particular, we show that as noise increases, the system undergoes P and D
bifurcations, transitioning from order to chaos. We ultimately characterize the
transition from stochastic (tonic) spiking to bursting by stochastic sensitivity
functions.
PMID- 29346915
TI - Efficient method for estimating the number of communities in a network.
AB - While there exist a wide range of effective methods for community detection in
networks, most of them require one to know in advance how many communities one is
looking for. Here we present a method for estimating the number of communities in
a network using a combination of Bayesian inference with a novel prior and an
efficient Monte Carlo sampling scheme. We test the method extensively on both
real and computer-generated networks, showing that it performs accurately and
consistently, even in cases where groups are widely varying in size or structure.
PMID- 29346916
TI - Construction of and efficient sampling from the simplicial configuration model.
AB - Simplicial complexes are now a popular alternative to networks when it comes to
describing the structure of complex systems, primarily because they encode
multinode interactions explicitly. With this new description comes the need for
principled null models that allow for easy comparison with empirical data. We
propose a natural candidate, the simplicial configuration model. The core of our
contribution is an efficient and uniform Markov chain Monte Carlo sampler for
this model. We demonstrate its usefulness in a short case study by investigating
the topology of three real systems and their randomized counterparts (using their
Betti numbers). For two out of three systems, the model allows us to reject the
hypothesis that there is no organization beyond the local scale.
PMID- 29346917
TI - Structural and dynamical characterization of water on the Au (100) and graphene
surfaces: A molecular dynamics simulation approach.
AB - The positioning, adsorption, and movement of water on substrates is dependent
upon the chemical nature and arrangement of the atoms of the surface. Therefore
the behavior of water molecules on a substrate is a reflection of properties of
the surface. Based on this premise, graphene and gold substrates were chosen to
study this subject from a molecular perspective. In this work, the structural and
dynamical behaviors of a water nanodroplet on Au (100) and the graphene
interfaces have been studied by molecular dynamics simulation. The results have
shown how the structural and dynamical behaviors of water molecules at the
interface reflect the characteristics of these surfaces. The results have
demonstrated that residence time and hydrogen bonds' lifetime at the water-Au
(100) interface are bigger than at the water-graphene interface. Energy contour
map analysis indicates a more uniform surface energy on graphene than on the gold
surface. The obtained results illustrate that water clusters on gold and graphene
form tetramer and hexamer structures, respectively. Furthermore, the water
molecules are more ordered on the gold surface than on graphene. The study of
hydrogen bonds showed that the order, stability, and the number of hydrogen bonds
is higher on the gold surface. The positioning pattern of water molecules is also
similar to the arrangement of gold atoms while no regularity was observed on
graphene. The study of dynamical behavior of water molecules revealed that the
movement of water on gold is much less than on graphene which is in agreement
with the strong water-gold interaction in comparison to the water-graphene
interaction.
PMID- 29346918
TI - Random walk to describe diffusion phenomena in three-dimensional discontinuous
media: Step-balance and fictitious-velocity corrections.
AB - In this paper, we show that diffusion phenomena in three-dimensional
discontinuous media can be described as a random walk by two simple interface
correction methods, namely step-balance and fictitious-velocity corrections,
which are completely different in a physical picture but equivalent in that the
continuity of the random walk at interfaces is considered. In both corrections,
asymmetric interface permeability of a random walker, which comes from ensuring
the continuity, causes apparent confinement of the walker in higher-diffusivity
layers for benchmark tests on heat diffusion in two-phase multilayered systems.
Effective thermal conductivities (walker diffusivities) computed from the
trajectories are in excellent agreement with the series and parallel conduction
formulas, indicating the equivalence of the two corrections and the importance of
ensuring the continuity of a random walk at interfaces.
PMID- 29346919
TI - Balancing building and maintenance costs in growing transport networks.
AB - The costs associated to the length of links impose unavoidable constraints to the
growth of natural and artificial transport networks. When future network
developments cannot be predicted, the costs of building and maintaining
connections cannot be minimized simultaneously, requiring competing optimization
mechanisms. Here, we study a one-parameter nonequilibrium model driven by an
optimization functional, defined as the convex combination of building cost and
maintenance cost. By varying the coefficient of the combination, the model
interpolates between global and local length minimization, i.e., between minimum
spanning trees and a local version known as dynamical minimum spanning trees. We
show that cost balance within this ensemble of dynamical networks is a sufficient
ingredient for the emergence of tradeoffs between the network's total length and
transport efficiency, and of optimal strategies of construction. At the
transition between two qualitatively different regimes, the dynamics builds up
power-law distributed waiting times between global rearrangements, indicating a
point of nonoptimality. Finally, we use our model as a framework to analyze
empirical ant trail networks, showing its relevance as a null model for cost
constrained network formation.
PMID- 29346920
TI - Conditional 1/f^{alpha} noise: From single molecules to macroscopic measurement.
AB - We demonstrate that the measurement of 1/f^{alpha} noise at the single molecule
or nano-object limit is remarkably distinct from the macroscopic measurement over
a large sample. The single-particle measurements yield a conditional time
dependent spectrum. However, the number of units fluctuating on the time scale of
the experiment is increasing in such a way that the macroscopic measurements
appear perfectly stationary. The single-particle power spectrum is a conditional
spectrum, in the sense that we must make a distinction between idler and nonidler
units on the time scale of the experiment. We demonstrate our results based on
stochastic and deterministic models, in particular the well-known approach of
superimposed Lorentzians, the blinking quantum dot model, and deterministic
dynamics generated by a nonlinear mapping. Our results show that the 1/f^{alpha}
spectrum is inherently nonstationary even if the macroscopic measurement
completely obscures the underlying time dependence of the phenomena.
PMID- 29346921
TI - Orthotropic hydraulic permeability of arrays of parallel cylinders.
AB - Approximate analytical methods are presented to calculate the overall orthotropic
hydraulic permeability of a flow with low Reynolds number, passing through a
bundle of parallel circular cylinders. Two particular distributions are
considered: (i) arrays with ordered rectangular lattices and (ii) irregular
nonrandom distributions for which the unit cell cross sections are elliptical.
The standard unit cell models, originally developed by Happel and Kuwabara for a
random distribution of cylinders, are adapted to the case of nonrandom
distributions. The drag force on a representative cylinder in a direction
perpendicular to its axis is obtained based on the standard unit cell model: the
actual unit cell of rectangular or elliptical cross section is replaced with an
"equivalent" cylindrical unit cell of diameter equal to the maximum width of the
actual unit cell. Using the obtained drag forces and referring back to the
original geometry of the unit cell, closed-form approximate expressions for the
overall permeabilities in the perpendicular directions are obtained. Numerical
comparisons with more sophisticated approaches confirm the good efficiency of the
presented approach, especially in the range of low solid volume fraction, i.e.,
of high porosity. Previous studies have revealed that, for the parallel fluid
flow, the variation of permeability with aspect ratio (or in general the lateral
arrangement) of parallel cylinders is generally weak. These observations suggest
that Happel's model for parallel permeability in a random distribution of
cylinders could be a good approximation for parallel permeabilities in nonrandom
distributions with the same volume fraction.
PMID- 29346922
TI - Effects of viscous heating and wall-fluid interaction energy on rate-dependent
slip behavior of simple fluids.
AB - Molecular dynamics simulations are used to investigate the rate and temperature
dependence of the slip length in thin liquid films confined by smooth, thermal
substrates. In our setup, the heat generated in a force-driven flow is removed by
the thermostat applied on several wall layers away from liquid-solid interfaces.
We found that for both high and low wall-fluid interaction (WFI) energies, the
temperature of the fluid phase rises significantly as the shear rate increases.
Surprisingly, with increasing shear rate, the slip length approaches a constant
value from above for high WFI energies and from below for low WFI energies. The
two distinct trends of the rate-dependent slip length are rationalized by
examining S(G_{1}), the height of the main peak of the in-plane structure factor
of the first fluid layer (FFL) together with D_{WF}, which is the average
distance between the wall and FFL. The results of numerical simulations
demonstrate that reduced values of the structure factor, S(G_{1}), correlate with
the enhanced slip, while smaller distances D_{WF} indicate that fluid atoms
penetrate deeper into the surface potential leading to larger friction and
smaller slip. Interestingly, at the lowest WFI energy, the combined effect of the
increase of S(G_{1}) and decrease of D_{WF} with increasing shear rate results in
a dramatic reduction of the slip length.
PMID- 29346923
TI - Unifying different interpretations of the nonlinear response in glass-forming
liquids.
AB - This work aims at reconsidering several interpretations coexisting in the recent
literature concerning nonlinear susceptibilities in supercooled liquids. We
present experimental results on glycerol and propylene carbonate, showing that
the three independent cubic susceptibilities have very similar frequency and
temperature dependences, for both their amplitudes and phases. This strongly
suggests a unique physical mechanism responsible for the growth of these
nonlinear susceptibilities. We show that the framework proposed by two of us [J.
P. Bouchaud and G. Biroli, Phys. Rev. B 72, 064204 (2005)PRBMDO1098
012110.1103/PhysRevB.72.064204], where the growth of nonlinear susceptibilities
is intimately related to the growth of glassy domains, accounts for all the
salient experimental features. We then review several complementary and/or
alternative models and show that the notion of cooperatively rearranging glassy
domains is a key (implicit or explicit) ingredient to all of them. This paves the
way for future experiments, which should deepen our understanding of glasses.
PMID- 29346924
TI - Multiclustered chimeras in large semiconductor laser arrays with nonlocal
interactions.
AB - The dynamics of a large array of coupled semiconductor lasers is studied
numerically for a nonlocal coupling scheme. Our focus is on chimera states, a
self-organized spatiotemporal pattern of coexisting coherence and incoherence. In
laser systems, such states have been previously found for global and nearest
neighbor coupling, mainly in small networks. The technological advantage of large
arrays has motivated us to study a system of 200 nonlocally coupled lasers with
respect to the emerging collective dynamics. Moreover, the nonlocal nature of the
coupling allows us to obtain robust chimera states with multiple (in)coherent
domains. The crucial parameters are the coupling strength, the coupling phase and
the range of the nonlocal interaction. We find that multiclustered chimera states
exist in a wide region of the parameter space and we provide quantitative
characterization for the obtained spatiotemporal patterns. By proposing two
different experimental setups for the realization of the nonlocal coupling
scheme, we are confident that our results can be confirmed in the laboratory.
PMID- 29346925
TI - Cluster sizes in a classical Lennard-Jones chain.
AB - The definitions of breaks and clusters in a one-dimensional chain in equilibrium
are discussed. Analytical expressions are obtained for the expected cluster
length, , as a function of temperature and pressure in a one-dimensional
Lennard-Jones chain. These expressions are compared with results from molecular
dynamics simulations. It is found that increases exponentially with
beta=1/k_{B}T and with pressure, P in agreement with previous results in the
literature. A method is illustrated for using (beta,P) to generate a "phase
diagram" for the Lennard-Jones chain. Some implications for the study of heat
transport in Lennard-Jones chains are discussed.
PMID- 29346926
TI - Convection induced by thermal gradients on thin reaction fronts.
AB - We present a thin front model for the propagation of chemical reaction fronts in
liquids inside a Hele-Shaw cell or porous media. In this model we take into
account density gradients due to thermal and compositional changes across a thin
interface. The front separating reacted from unreacted fluids evolves following
an eikonal relation between the normal speed and the curvature. We carry out a
linear stability analysis of convectionless flat fronts confined in a two
dimensional rectangular domain. We find that all fronts are stable to
perturbations of short wavelength, but they become unstable for some wavelengths
depending on the values of compositional and thermal gradients. If the effects of
these gradients oppose each other, we observe a range of wavelengths that make
the flat front unstable. Numerical solutions of the nonlinear model show curved
fronts of steady shape with convection propagating faster than flat fronts.
Exothermic fronts increase the temperature of the fluid as they propagate through
the domain. This increment in temperature decreases with increasing speed.
PMID- 29346927
TI - Topological inversions in coalescing granular media control fluid-flow regimes.
AB - Sintering-or coalescence-of viscous droplets is an essential process in many
natural and industrial scenarios. Current physical models of the dynamics of
sintering are limited by the lack of an explicit account of the evolution of
microstructural geometry. Here, we use high-speed time-resolved x-ray tomography
to image the evolving geometry of a sintering system of viscous droplets, and use
lattice Boltzmann simulations of creeping fluid flow through the reconstructed
pore space to determine its permeability. We identify and characterize a
topological inversion, from spherical droplets in a continuous interstitial gas,
to isolated bubbles in a continuous liquid. We find that the topological
inversion is associated with a transition in permeability-porosity behavior, from
Stokes permeability at high porosity, to percolation theory at low porosity. We
use these findings to construct a unified physical description that reconciles
previously incompatible models for the evolution of porosity and permeability
during sintering.
PMID- 29346928
TI - Signatures of classical structures in the leading eigenstates of quantum
dissipative systems.
AB - By analyzing a paradigmatic example of the theory of dissipative systems-the
classical and quantum dissipative standard map-we are able to explain the main
features of the decay to the quantum equilibrium state. The classical isoperiodic
stable structures typically present in the parameter space of these kinds of
systems play a fundamental role. In fact, we have found that the period of stable
structures that are near in this space determines the phase of the leading
eigenstates of the corresponding quantum superoperator. Moreover, the
eigenvectors show a strong localization on the corresponding periodic orbits
(limit cycles). We show that this sort of scarring phenomenon (an established
property of Hamiltonian and projectively open systems) is present in the
dissipative case and it is of extreme simplicity.
PMID- 29346929
TI - Numerical estimation of structure constants in the three-dimensional Ising
conformal field theory through Markov chain uv sampler.
AB - Herdeiro and Doyon [Phys. Rev. E 94, 043322 (2016)2470
004510.1103/PhysRevE.94.043322] introduced a numerical recipe, dubbed uv sampler,
offering precise estimations of the conformal field theory (CFT) data of the
planar two-dimensional (2D) critical Ising model. It made use of scale invariance
emerging at the critical point in order to sample finite sublattice marginals of
the infinite plane Gibbs measure of the model by producing holographic boundary
distributions. The main ingredient of the Markov chain Monte Carlo sampler is the
invariance under dilation. This paper presents a generalization to higher
dimensions with the critical 3D Ising model. This leads to numerical estimations
of a subset of the CFT data-scaling weights and structure constants-through
fitting of measured correlation functions. The results are shown to agree with
the recent most precise estimations from numerical bootstrap methods [Kos,
Poland, Simmons-Duffin, and Vichi, J. High Energy Phys. 08 (2016)
03610.1007/JHEP08(2016)036].
PMID- 29346930
TI - Proxy-equation paradigm: A strategy for massively parallel asynchronous
computations.
AB - Massively parallel simulations of transport equation systems call for a paradigm
change in algorithm development to achieve efficient scalability. Traditional
approaches require time synchronization of processing elements (PEs), which
severely restricts scalability. Relaxing synchronization requirement introduces
error and slows down convergence. In this paper, we propose and develop a novel
"proxy equation" concept for a general transport equation that (i) tolerates
asynchrony with minimal added error, (ii) preserves convergence order and thus,
(iii) expected to scale efficiently on massively parallel machines. The central
idea is to modify a priori the transport equation at the PE boundaries to offset
asynchrony errors. Proof-of-concept computations are performed using a one
dimensional advection (convection) diffusion equation. The results demonstrate
the promise and advantages of the present strategy.
PMID- 29346931
TI - Equation-based model for the stock market.
AB - We propose a stock market model which is investigated in the forms of difference
and differential equations whose variables correspond to the demand or supply of
each agent and to the price. In the model, agents are driven by the behavior of
their trust contact network as well by fundamental analysis. By means of the
deterministic version of the model, the connection between such drive mechanisms
and the price is analyzed: imitation behavior promotes market instability,
finitude of resources is associated to stock index stability, and high
sensitivity to the fair price provokes price oscillations. Long-range
correlations in the price temporal series and heavy-tailed distribution of
returns are observed for the version of the model which considers different
proposals for stochasticity of microeconomic and macroeconomic origins.
PMID- 29346932
TI - Gap-junction coupling and ATP-sensitive potassium channels in human beta-cell
clusters: Effects on emergent dynamics.
AB - The importance of gap-junction coupling between beta cells in pancreatic islets
is well established in mouse. Such ultrastructural connections synchronize
cellular activity, confine biological heterogeneity, and enhance insulin
pulsatility. Dysfunction of coupling has been associated with diabetes and
altered beta-cell function. However, the role of gap junctions between human beta
cells is still largely unexplored. By using patch-clamp recordings of beta cells
from human donors, we previously estimated electrical properties of these
channels by mathematical modeling of pairs of human beta cells. In this work we
revise our estimate by modeling triplet configurations and larger heterogeneous
clusters. We find that a coupling conductance in the range 0.005-0.020 nS/pF can
reproduce experiments in almost all the simulated arrangements. We finally
explore the consequence of gap-junction coupling of this magnitude between beta
cells with mutant variants of the ATP-sensitive potassium channels involved in
some metabolic disorders and diabetic conditions, translating studies performed
on rodents to the human case. Our results are finally discussed from the
perspective of therapeutic strategies. In summary, modeling of more realistic
clusters with more than two beta cells slightly lowers our previous estimate of
gap-junction conductance and gives rise to patterns that more closely resemble
experimental traces.
PMID- 29346933
TI - Internal temperature of quantum chaotic systems at the nanoscale.
AB - The extent to which a temperature can be appropriately assigned to a small
quantum system, as an internal property but not as a property of any large
environment, is still an open problem. In this paper, a method is proposed for
solving this problem, by which a studied small system is coupled to a two-level
system as a probe, the latter of which can be measured by measurement devices. A
main difficulty in the determination of possible temperature of the studied
system comes from the back-action of the probe-system coupling to the system. For
small quantum chaotic systems, we show that a temperature can be determined, the
value of which is sensitive to neither the form, location, and strength of the
probe-system coupling, nor the Hamiltonian and initial state of the probe. The
temperature thus obtained turns out to have the form of Boltzmann temperature.
PMID- 29346934
TI - Kardar-Parisi-Zhang modes in d-dimensional directed polymers.
AB - We define a stochastic lattice model for a fluctuating directed polymer in d>=2
dimensions. This model can be alternatively interpreted as a fluctuating random
path in two dimensions, or a one-dimensional asymmetric simple exclusion process
with d-1 conserved species of particles. The deterministic large dynamics of the
directed polymer are shown to be given by a system of coupled Kardar-Parisi-Zhang
(KPZ) equations and diffusion equations. Using nonlinear fluctuating
hydrodynamics and mode coupling theory we argue that stationary fluctuations in
any dimension d can only be of KPZ type or diffusive. The modes are pure in the
sense that there are only subleading couplings to other modes, thus excluding the
occurrence of modified KPZ-fluctuations or Levy-type fluctuations, which are
common for more than one conservation law. The mode-coupling matrices are shown
to satisfy the so-called trilinear condition.
PMID- 29346935
TI - Chase-and-run dynamics in cell motility and the molecular rupture of interacting
active elastic dimers.
AB - Cell migration in morphogenesis and cancer metastasis typically involves
interplay between different cell types. We construct and study a minimal, one
dimensional model composed of two different motile cells with each cell
represented as an active elastic dimer. The interaction between the two cells via
cadherins is modeled as a spring that can rupture beyond a threshold force as it
undergoes dynamic loading from the interacting motile cells. We obtain a phase
diagram consisting of chase-and-run dynamics and clumping dynamics as a function
of the stiffness of the interaction spring and the threshold force and,
therefore, posit that active rupture, or rupture via active forces, is a
mechanosensitive means to regulate dynamics between cells. Since the parameters
in the model differentiate between N- and E-cadherins, we make predictions for
the interactions between a placodelike cell and a neural crestlike cell in a
microchannel as well as discuss how our results inform chase-and-run dynamics
found in a group of placode cells interacting with a group of neural crest cells.
In particular, an argument was made in the latter case that the feedback between
cadherins and cell-substrate interaction via integrins was necessary to obtain
the chase-and-run behavior. Based on our two-cell results, we argue that this
feedback accentuates, but is not necessary for, the chase-and-run behavior.
PMID- 29346936
TI - Accessibility and delay in random temporal networks.
AB - In a wide range of complex networks, the links between the nodes are temporal and
may sporadically appear and disappear. This temporality is fundamental to
analyzing the formation of paths within such networks. Moreover, the presence of
the links between the nodes is a random process induced by nature in many real
world networks. In this paper, we study random temporal networks at a microscopic
level and formulate the probability of accessibility from a node i to a node j
after a certain number of discrete time units T. While solving the original
problem is computationally intractable, we provide an upper and two lower bounds
on this probability for a very general case with arbitrary time-varying
probabilities of the links' existence. Moreover, for a special case where the
links have identical probabilities across the network at each time slot, we
obtain the exact probability of accessibility between any two nodes. Finally, we
discuss scenarios where the information regarding the presence and absence of
links is initially available in the form of time duration (of presence or absence
intervals) continuous probability distributions rather than discrete
probabilities over time slots. We provide a method for transforming such
distributions to discrete probabilities, which enables us to apply the given
bounds in this paper to a broader range of problem settings.
PMID- 29346937
TI - Uhlenbeck-Ford model: Phase diagram and corresponding-states analysis.
AB - Using molecular dynamics simulations and nonequilibrium thermodynamic-integration
techniques we compute the Helmholtz free energies of the body-centered-cubic
(bcc), face-centered-cubic (fcc), hexagonal close-packed, and fluid phases of the
Uhlenbeck-Ford model (UFM) and use the results to construct its phase diagram.
The pair interaction associated with the UFM is characterized by an ultrasoft,
purely repulsive pair potential that diverges logarithmically at the origin. We
find that the bcc and fcc are the only thermodynamically stable crystalline
phases in the phase diagram. Furthermore, we report the existence of two
reentrant transition sequences as a function of the number density, one featuring
a fluid-bcc-fluid succession and another displaying a bcc-fcc-bcc sequence near
the triple point. We find strong resemblances to the phase behavior of other
soft, purely repulsive systems such as the Gaussian-core model (GCM), inverse
power-law, and Yukawa potentials. In particular, we find that the fcc-bcc-fluid
triple point and the phase boundaries in its vicinity are in good agreement with
the prediction supplied by a recently proposed corresponding-states principle [J.
Chem. Phys. 134, 241101 (2011)JCPSA60021-960610.1063/1.3605659; Europhys. Lett.
100, 66004 (2012)EULEEJ0295-507510.1209/0295-5075/100/66004]. The particularly
strong resemblance between the behavior of the UFM and GCM models are also
discussed.
PMID- 29346938
TI - Equilibrium position of a rigid sphere in a turbulent jet: A problem of elastic
reconfiguration.
AB - The position of floating spheres trapped within an immersed turbulent water jet
is investigated. Using the self-similarity properties of the jet velocity
profile, the equilibrium problem is formulated in a rescaled space where the
sphere is static and deformable. This approach is found to be related to a
problem of elastic reconfiguration where elasticity arises here from the geometry
of the flow instead of an actual deformation of a body.
PMID- 29346939
TI - Promoting information diffusion through interlayer recovery processes in
multiplex networks.
AB - For information diffusion in multiplex networks, the effect of interlayer
contagion on spreading dynamics has been explored in different settings.
Nevertheless, the impact of interlayer recovery processes, i.e., the transition
of nodes to stiflers in all layers after they become stiflers in any layer, still
remains unclear. In this paper, we propose a modified ignorant-spreader-stifler
model of rumor spreading equipped with an interlayer recovery mechanism. We find
that the information diffusion can be effectively promoted for a range of
interlayer recovery rates. By combining the mean-field approximation and the
Markov chain approach, we derive the evolution equations of the diffusion process
in two-layer homogeneous multiplex networks. The optimal interlayer recovery rate
that achieves the maximal enhancement can be calculated by solving the equations
numerically. In addition, we find that the promoting effect on a certain layer
can be strengthened if information spreads more extensively within the
counterpart layer. When applying the model to two-layer scale-free multiplex
networks, with or without degree correlation, similar promoting effect is also
observed in simulations. Our work indicates that the interlayer recovery process
is beneficial to information diffusion in multiplex networks, which may have
implications for designing efficient spreading strategies.
PMID- 29346940
TI - Advective superdiffusion in superhydrophobic microchannels.
AB - We consider pressure-driven flows in wide microchannels, and discuss how a
transverse shear, generated by misaligned superhydrophobic walls, impacts cross
sectional spreading of Brownian particles. We show that such a transverse shear
can induce an advective superdiffusion, which strongly enhances dispersion of
particles compared to a normal diffusion, and that maximal cross-sectional
spreading corresponds to a crossover between its subballistic and superballistic
regimes. This allows us to argue that an advective superdiffusion can be used for
boosting dispersion of particles at smaller Peclet numbers compared to known
concepts of passive microfluidic mixing. This implies that our superdiffusion
scenario allows one efficient mixing of much smaller particles or using much
thinner microchannels than methods, which are currently being exploited.
PMID- 29346941
TI - Phase transition in the singularity spectrum of an intermingled basin.
AB - A two-dimensional piecewise linear mapping is introduced as a solvable model to
characterize the multifractal structure of an intermingled basin. To this end, we
make use of the multifractal formalism and introduce a partition function. The
singularity spectrum, which characterizes local scaling property of the
intermingled basin, is then determined. We have found that if the system is not
symmetric, the singularity spectrum of either basin shows a phase transition,
corresponding to the existence of two phases the orbits experience in the system,
i.e., local one governed by the chaotic motions on the chaotic attractor, and the
other global one reflecting nonhyperbolic motions characteristic of the
intermingled basin.
PMID- 29346942
TI - Transitions in optimal adaptive strategies for populations in fluctuating
environments.
AB - Biological populations are subject to fluctuating environmental conditions.
Different adaptive strategies can allow them to cope with these fluctuations:
specialization to one particular environmental condition, adoption of a
generalist phenotype that compromises between conditions, or population-wise
diversification (bet hedging). Which strategy provides the largest selective
advantage in the long run depends on the range of accessible phenotypes and the
statistics of the environmental fluctuations. Here, we analyze this problem in a
simple mathematical model of population growth. First, we review and extend a
graphical method to identify the nature of the optimal strategy when the
environmental fluctuations are uncorrelated. Temporal correlations in
environmental fluctuations open up new strategies that rely on memory but are
mathematically challenging to study: We present analytical results to address
this challenge. We illustrate our general approach by analyzing optimal adaptive
strategies in the presence of trade-offs that constrain the range of accessible
phenotypes. Our results extend several previous studies and have applications to
a variety of biological phenomena, from antibiotic resistance in bacteria to
immune responses in vertebrates.
PMID- 29346943
TI - Whitham modulation theory for the two-dimensional Benjamin-Ono equation.
AB - Whitham modulation theory for the two-dimensional Benjamin-Ono (2DBO) equation is
presented. A system of five quasilinear first-order partial differential
equations is derived. The system describes modulations of the traveling wave
solutions of the 2DBO equation. These equations are transformed to a singularity
free hydrodynamic-like system referred to here as the 2DBO-Whitham system. Exact
reductions of this system are discussed, the formulation of initial value
problems is considered, and the system is used to study the transverse stability
of traveling wave solutions of the 2DBO equation.
PMID- 29346944
TI - Phase transition and power-law coarsening in an Ising-doped voter model.
AB - We examine an opinion formation model, which is a mixture of Voter and Ising
agents. Numerical simulations show that even a very small fraction (~1%) of the
Ising agents drastically changes the behavior of the Voter model. The Voter
agents act as a medium, which correlates sparsely dispersed Ising agents, and the
resulting ferromagnetic ordering persists up to a certain temperature. Upon
addition of the Ising agents, a logarithmically slow coarsening of the Voter
model (d=2), or its active steady state (d=3), change into an Ising-type power
law coarsening.
PMID- 29346945
TI - Nonmonotonic dependence of polymer-glass mechanical response on chain bending
stiffness.
AB - We investigate the mechanical properties of amorphous polymers by means of coarse
grained simulations and nonaffine lattice dynamics theory. A small increase of
polymer chain bending stiffness leads first to softening of the material, while
hardening happens only upon further strengthening of the backbones. This
nonmonotonic variation of the storage modulus G^{'} with bending stiffness is
caused by a competition between additional resistance to deformation offered by
stiffer backbones and decreased density of the material due to a necessary
decrease in monomer-monomer coordination. This counterintuitive finding suggests
that the strength of polymer glasses may in some circumstances be enhanced by
softening the bending of constituent chains.
PMID- 29346946
TI - Flow and clog in a silo with oscillating exit.
AB - When grains flow out of a silo, flow rate W increases with exit size D. If D is
too small, an arch may form and the flow may be blocked at the exit. To recover
from clogging, the arch has to be destroyed. Here we construct a two-dimensional
silo with movable exit and study the effects of exit oscillation (with amplitude
A and frequency f) on flow rate, clogging, and unclogging of grains through the
exit. We find that, if exit oscillates, W remains finite even when D (measured in
unit of grain diameter) is only slightly larger than one. Surprisingly, while W
increases with oscillation strength Gamma=4pi^{2}Af^{2} as expected at small D, W
decreases with Gamma when D>=5 due to induced random motion of the grains at the
exit. When D is small and oscillation speed v=2piAf is slow, temporary clogging
events cause the grains to flow intermittently. In this regime, W depends only on
v-a feature consistent to a simple arch breaking mechanism, and the phase
boundary of intermittent flow in the D-v plane is consistent to either a power
law: D?v^{-7} or an exponential form: D?e^{-D/0.55}. Furthermore, the flow time
statistic is Poissonian whereas the recovery time statistic follows a power-law
distribution.
PMID- 29346947
TI - Bragg solitons in systems with separated nonuniform Bragg grating and
nonlinearity.
AB - The existence and stability of quiescent Bragg grating solitons are
systematically investigated in a dual-core fiber, where one of the cores is
uniform and has Kerr nonlinearity while the other one is linear and incorporates
a Bragg grating with dispersive reflectivity. Three spectral gaps are identified
in the system, in which both lower and upper band gaps overlap with one branch of
the continuous spectrum; therefore, these are not genuine band gaps. However, the
central band gap is a genuine band gap. Soliton solutions are found in the lower
and upper gaps only. It is found that in certain parameter ranges, the solitons
develop side lobes. To analyze the side lobes, we have derived exact analytical
expressions for the tails of solitons that are in excellent agreement with the
numerical solutions. We have analyzed the stability of solitons in the system by
means of systematic numerical simulations. We have found vast stable regions in
the upper and lower gaps. The effect and interplay of dispersive reflectivity,
the group velocity difference, and the grating-induced coupling on the stability
of solitons are investigated. A key finding is that a stronger grating-induced
coupling coefficient counteracts the stabilization effect of dispersive
reflectivity.
PMID- 29346948
TI - Regularized fractional Ornstein-Uhlenbeck processes and their relevance to the
modeling of fluid turbulence.
AB - Motivated by the modeling of the temporal structure of the velocity field in a
highly turbulent flow, we propose and study a linear stochastic differential
equation that involves the ingredients of an Ornstein-Uhlenbeck process,
supplemented by a fractional Gaussian noise, of parameter H, regularized over a
(small) time scale epsilon>0. A peculiar correlation between these two plays a
key role in the establishment of the statistical properties of its solution. We
show that this solution reaches a stationary regime, which marginals, including
variance and increment variance, remain bounded when epsilon->0. In particular,
in this limit, for any H?]0,1[, we show that the increment variance behaves at
small scales as the one of a fractional Brownian motion of same parameter H. From
the theoretical side, this approach appears especially well suited to deal with
the (very) rough case H<1/2, including the boundary value H=0, and to design
simple and efficient numerical simulations.
PMID- 29346949
TI - Hyperuniformity disorder length spectroscopy for extended particles.
AB - The concept of a hyperuniformity disorder length h was recently introduced for
analyzing volume fraction fluctuations for a set of measuring windows [Chieco et
al., Phys. Rev. E 96, 032909 (2017).PLEEE81539-375510.1103/PhysRevE.96.032909].
This length permits a direct connection to the nature of disorder in the spatial
configuration of the particles and provides a way to diagnose the degree of
hyperuniformity in terms of the scaling of h and its value in comparison with
established bounds. Here, this approach is generalized for extended particles,
which are larger than the image resolution and can lie partially inside and
partially outside the measuring windows. The starting point is an expression for
the relative volume fraction variance in terms of four distinct volumes: that of
the particle, the measuring window, the mean-squared overlap between particle and
region, and the region over which particles have nonzero overlap with the
measuring window. After establishing limiting behaviors for the relative
variance, computational methods are developed for both continuum and pixelated
particles. Exact results are presented for particles of special shape and for
measuring windows of special shape, for which the equations are tractable.
Comparison is made for other particle shapes, using simulated Poisson patterns.
And the effects of polydispersity and image errors are discussed. For small
measuring windows, both particle shape and spatial arrangement affect the form of
the variance. For large regions, the variance scaling depends only on arrangement
but particle shape sets the numerical proportionality. The combined understanding
permit the measured variance to be translated to the spectrum of hyperuniformity
lengths versus region size, as the quantifier of spatial arrangement. This
program is demonstrated for a system of nonoverlapping particles at a series of
increasing packing fractions as well as for an Einstein pattern of particles with
several different extended shapes.
PMID- 29346950
TI - Generalized Archimedes' principle in active fluids.
AB - We show how a gradient in the motility properties of noninteracting pointlike
active particles can cause a pressure gradient that pushes a large inert object.
We calculate the force on an object inside a system of active particles with
position-dependent motion parameters, in one and two dimensions, and show that a
modified Archimedes' principle is satisfied. We characterize the system, both in
terms of the model parameters and in terms of experimentally measurable
quantities: the spatial profiles of the density, velocity and pressure. This
theoretical analysis is motivated by recent experiments, which showed that the
nucleus of a mouse oocyte (immature egg cell) moves from the cortex to the center
due to a gradient of activity of vesicles propelled by molecular motors; it more
generally applies to artificial systems of controlled localized activity.
PMID- 29346951
TI - Universal exponent for transport in mixed Hamiltonian dynamics.
AB - We compute universal distributions for the transition probabilities of a Markov
model for transport in the mixed phase space of area-preserving maps and verify
that the survival probability distribution for trajectories near an infinite
island-around-island hierarchy exhibits, on average, a power-law decay with
exponent gamma=1.57. This exponent agrees with that found from simulations of the
Henon and Chirikov-Taylor maps. This provides evidence that the Meiss-Ott Markov
tree model describes the transport for mixed systems.
PMID- 29346952
TI - Fluctuations in an established transmission in the presence of a complex
environment.
AB - In various situations where wave transport is preeminent, like in wireless
communication, a strong established transmission is present in a complex
scattering environment. We develop a nonperturbative approach to describe
emerging fluctuations which combines a transmitting channel and a chaotic
background in a unified effective Hamiltonian. Modeling such a background by
random matrix theory, we derive exact results for both transmission and
reflection distributions at arbitrary absorption that is typically present in
real systems. Remarkably, in such a complex scattering situation, the transport
is governed by only two parameters: an absorption rate and the ratio of the so
called spreading width to the natural width of the transmission line. In
particular, we find that the established transmission disappears sharply when
this ratio exceeds unity. The approach exemplifies the role of the chaotic
background in dephasing the deterministic scattering.
PMID- 29346953
TI - Quantum statistical effects in the mass transport of interstitial solutes in a
crystalline solid.
AB - The impact of quantum statistics on the many-body dynamics of a crystalline solid
at finite temperatures containing an interstitial solute atom (ISA) is
investigated. The Mori-Zwanzig theory allows the many-body dynamics of the
crystal to be formulated and solved analytically within a pseudo-one-particle
approach using the Langevin equation with a quantum fluctuation-dissipation
relation (FDR) based on the Debye model. At the same time, the many-body dynamics
is also directly solved numerically via the molecular dynamics approach with a
Langevin heat bath based on the quantum FDR. Both the analytical and numerical
results consistently show that below the Debye temperature of the host lattice,
quantum statistics significantly impacts the ISA transport properties, resulting
in major departures from both the Arrhenius law of diffusion and the Einstein
Smoluchowski relation between the mobility and diffusivity. Indeed, we found that
below one-third of the Debye temperature, effects of vibrations on the quantum
mobility and diffusivity are both orders-of-magnitude larger and practically
temperature independent. We have shown that both effects have their physical
origin in the athermal lattice vibrations derived from the phonon ground state.
The foregoing theory is tested in quantum molecular dynamics calculation of
mobility and diffusivity of interstitial helium in bcc W. In this case, the
Arrhenius law is only valid in a narrow range between ~300 and ~700 K. The
diffusivity becomes temperature independent on the low-temperature side while
increasing linearly with temperature on the high-temperature side.
PMID- 29346954
TI - Dynamical pattern selection of growing cellular mosaic in fish retina.
AB - A Markovian lattice model for photoreceptor cells is introduced to describe the
growth of mosaic patterns on fish retina. The radial stripe pattern observed in
wild-type zebrafish is shown to be selected naturally during retina growth,
against the geometrically equivalent circular stripe pattern. The mechanism of
such dynamical pattern selection is clarified on the basis of both numerical
simulations and theoretical analyses, which find that the successive emergence of
local defects plays a critical role in the realization of the wild-type pattern.
PMID- 29346955
TI - Ehrenfest urn model with interaction.
AB - We studied the Ehrenfest urn model in which particles in the same urn interact
with each other. Depending on the nature of interaction, the system undergoes a
first- or second-order phase transition. The relaxation time to the equilibrium
state, the Poincare cycles of the equilibrium state and the most far-from
equilibrium state, and the duration time of the states during first-order phase
transition are calculated. It was shown that the scaling behavior the Poincare
cycles could serve as an indication to the nature of phase transition, and the
behavior of the ratio of duration time of the states could be strong evidence of
the metastability during first-order phase transition.
PMID- 29346956
TI - Pseudoinverse of the Laplacian and best spreader node in a network.
AB - Determining a set of "important" nodes in a network constitutes a basic endeavor
in network science. Inspired by electrical flows in a resistor network, we
propose the best conducting node j in a graph G as the minimizer of the diagonal
element Q_{jj}^{?} of the pseudoinverse matrix Q^{?} of the weighted Laplacian
matrix of the graph G. We propose a new graph metric that complements the
effective graph resistance R_{G} and that specifies the heterogeneity of the
nodal spreading capacity in a graph. Various formulas and bounds for the diagonal
element Q_{jj}^{?} are presented. Finally, we compute the pseudoinverse matrix of
the Laplacian of star, path, and cycle graphs and derive an expansion and lower
bound of the effective graph resistance R_{G} based on the complement of the
graph G.
PMID- 29346957
TI - Double transition in a model of oscillating percolation.
AB - Two distinct transition points have been observed in a problem of lattice
percolation studied using a system of pulsating disks. Sites on a regular lattice
are occupied by circular disks whose radii vary sinusoidally within [0,R_{0}]
starting from a random distribution of phase angles. A lattice bond is said to be
connected when its two end disks overlap with each other. Depending on the
difference of the phase angles of these disks, a bond may be termed as dead or
live. While a dead bond can never be connected, a live bond is connected at least
once in a complete time period. Two different time scales can be associated with
such a system, leading to two transition points. Namely, a percolation transition
occurs at R_{0c}=0.908(5) when a spanning cluster of connected bonds emerges in
the system. Here, information propagates across the system instantly, i.e., with
infinite speed. Secondly, there exists another transition point
R_{0}^{*}=0.5907(3) where the giant cluster of live bonds spans the lattice. In
this case the information takes finite time to propagate across the system
through the dynamical evolution of finite-size clusters. This passage time
diverges as R_{0}->R_{0}^{*} from above. Both the transitions exhibit the
critical behavior of ordinary percolation transition. The entire scenario is
robust with respect to the distribution of frequencies of the individual disks.
This study may be relevant in the context of wireless sensor networks.
PMID- 29346958
TI - Electroclinic effect in chiral smectic-A liquid crystal elastomers.
AB - Chiral smectic-A liquid crystal elastomers are rubbery materials composed of a
lamellar arrangement of liquid crystalline mesogens. It has been shown
experimentally that these materials shear when subjected to an electric field due
to the electrically induced tilt of the director. Experiments have also shown
that shearing a chiral smectic-A elastomer gives rise to a polarization. Roughly,
the shear force tilts the directors which, in turn, induce electric dipoles. This
paper builds on previous works and models the electromechanical response of
smectic-A elastomers using free energy contributions that are associated with the
lamellar structure, the relative tilt between the director and the layer normal,
and the coupling between the director and the electric field. To illustrate the
merit of the proposed model, two cases are considered-a deformation induced
polarization and an electrically induced deformation. The predictions according
to these two models qualitatively agree with experimental findings. Finally, a
cylinder composed of helical smectic layers is also considered. It is shown that
the electromechanical response varies as a function of the helix angle.
PMID- 29346959
TI - Complex free-energy landscapes in biaxial nematic liquid crystals and the role of
repulsive interactions: A Wang-Landau study.
AB - General quadratic Hamiltonian models, describing the interaction between liquid
crystal molecules (typically with D_{2h} symmetry), take into account couplings
between their uniaxial and biaxial tensors. While the attractive contributions
arising from interactions between similar tensors of the participating molecules
provide for eventual condensation of the respective orders at suitably low
temperatures, the role of cross coupling between unlike tensors is not fully
appreciated. Our recent study with an advanced Monte Carlo technique (entropic
sampling) showed clearly the increasing relevance of this cross term in
determining the phase diagram (contravening in some regions of model parameter
space), the predictions of mean-field theory, and standard Monte Carlo simulation
results. In this context, we investigated the phase diagrams and the nature of
the phases therein on two trajectories in the parameter space: one is a line in
the interior region of biaxial stability believed to be representative of the
real systems, and the second is the extensively investigated parabolic path
resulting from the London dispersion approximation. In both cases, we find the
destabilizing effect of increased cross-coupling interactions, which invariably
result in the formation of local biaxial organizations inhomogeneously
distributed. This manifests as a small, but unmistakable, contribution of biaxial
order in the uniaxial phase. The free-energy profiles computed in the present
study as a function of the two dominant order parameters indicate complex
landscapes. On the one hand, these profiles account for the unusual thermal
behavior of the biaxial order parameter under significant destabilizing influence
from the cross terms. On the other, they also allude to the possibility that in
real systems, these complexities might indeed be inhibiting the formation of a
low-temperature biaxial order itself-perhaps reflecting the difficulties in their
ready realization in the laboratory.
PMID- 29346960
TI - Chimera and modulated drift states in a ring of nonlocally coupled oscillators
with heterogeneous phase lags.
AB - We consider a ring of phase oscillators with nonlocal coupling strength and
heterogeneous phase lags. We analyze the effects of heterogeneity in the phase
lags on the existence and stability of a variety of steady states. A nonlocal
coupling with heterogeneous phase lags that allows the system to be solved
analytically is suggested and the stability of solutions along the Ott-Antonsen
invariant manifold is explored. We present a complete bifurcation diagram for
stationary patterns including the uniform drift and modulated drift states as
well as chimera state, which reveals that the stable modulated drift state and a
continuum of metastable drift states could occur due to the heterogeneity of the
phase lags. We verify our theoretical results using the direct numerical
simulations of the model system.
PMID- 29346961
TI - Photonic band structure of diamond colloidal crystals in a cholesteric liquid
crystal.
AB - In this paper, we demonstrate the presence of a photonic band gap for a diamond
lattice structure made of particles with normal anchoring inside a cholesteric
liquid crystal. As is typical for liquid crystals (LCs), there is considerable
contrast between the dielectric constant parallel epsilon_{?} and perpendicular
epsilon_{?} to the director, with epsilon_{?}/epsilon_{?}~4 here. It is shown
that the size of the photonic band gap is directly related to the size of
colloidal particles and the contrast between the dielectric constant in the
particles and the extreme values of epsilon in the LC medium (one needs either
epsilon in the particle much smaller than epsilon_{?} or much bigger than
epsilon_{?}). No opening is seen in the band diagrams for small particles. For
larger particles a partial gap opens when the particles are composed of very low
dielectric material but never a complete gap. On the other hand, a complete gap
starts to be revealed when the size of the colloidal particles is increased and
when a high dielectric constant is used for filling inside the particles. The
maximum size of the gap is observed when the particles are large enough so that
their surfaces overlap.
PMID- 29346962
TI - Osmotic mechanism of the loop extrusion process.
AB - The loop extrusion theory assumes that protein factors, such as cohesin rings,
act as molecular motors that extrude chromatin loops. However, recent single
molecule experiments have shown that cohesin does not show motor activity. To
predict the physical mechanism involved in loop extrusion, we here theoretically
analyze the dynamics of cohesin rings on a loop, where a cohesin loader is in the
middle and unloaders at the ends. Cohesin monomers bind to the loader rather
frequently and cohesin dimers bind to this site only occasionally. Our theory
predicts that a cohesin dimer extrudes loops by the osmotic pressure of cohesin
monomers on the chromatin fiber between the two connected rings. With this
mechanism, the frequency of the interactions between chromatin segments depends
on the loading and unloading rates of dimers at the corresponding sites.
PMID- 29346963
TI - Publisher's Note: Oscillatory motion of a camphor grain in a one-dimensional
finite region [Phys. Rev. E 94, 042215 (2016)].
AB - This corrects the article DOI: 10.1103/PhysRevE.94.042215.
PMID- 29346964
TI - Predictability of fat-tailed extremes.
AB - We conjecture for a linear stochastic differential equation that the
predictability of threshold exceedances (I) improves with the event magnitude
when the noise is a so-called correlated additive-multiplicative noise, no matter
the nature of the stochastic innovations, and also improves when (II) the noise
is purely additive, obeying a distribution that decays fast, i.e., not by a power
law, and (III) deteriorates only when the additive noise distribution follows a
power law. The predictability is measured by a summary index of the receiver
operating characteristic curve. We provide support to our conjecture-to
compliment reports in the existing literature on (II)-by a set of case studies.
Calculations for the prediction skill are conducted in some cases by a direct
numerical time-series-data-driven approach and in other cases by an analytical or
semianalytical approach developed here.
PMID- 29346965
TI - Solute-mediated interactions between active droplets.
AB - Concentration gradients play a critical role in embryogenesis, bacterial
locomotion, as well as the motility of active particles. Particles develop
concentration profiles around them by dissolution, adsorption, or the reactivity
of surface species. These gradients change the surface energy of the particles,
driving both their self-propulsion and governing their interactions. Here, we
uncover a regime in which solute gradients mediate interactions between slowly
dissolving droplets without causing autophoresis. This decoupling allows us to
directly measure the steady-state, repulsive force, which scales with
interparticle distance as F~1/r^{2}. Our results show that the dissolution
process is diffusion rather than reaction rate limited, and the theoretical model
captures the dependence of the interactions on droplet size and solute
concentration, using a single fit parameter, l=16+/-3nm, which corresponds to the
length scale of a swollen micelle. Our results shed light on the out-of
equilibrium behavior of particles with surface reactivity.
PMID- 29346966
TI - Systematic dimensionality reduction for continuous-time quantum walks of
interacting fermions.
AB - To extend the continuous-time quantum walk (CTQW) to simulate P distinguishable
particles on a graph G composed of N vertices, the Hamiltonian of the system is
expanded to act on an N^{P}-dimensional Hilbert space, in effect, simulating the
multiparticle CTQW on graph G via a single-particle CTQW propagating on the
Cartesian graph product G^{?P}. The properties of the Cartesian graph product
have been well studied, and classical simulation of multiparticle CTQWs are
common in the literature. However, the above approach is generally applied as is
when simulating indistinguishable particles, with the particle statistics then
applied to the propagated N^{P} state vector to determine walker probabilities.
We address the following question: How can we modify the underlying graph
structure G^{?P} in order to simulate multiple interacting fermionic CTQWs with a
reduction in the size of the state space? In this paper, we present an algorithm
for systematically removing "redundant" and forbidden quantum states from
consideration, which provides a significant reduction in the effective dimension
of the Hilbert space of the fermionic CTQW. As a result, as the number of
interacting fermions in the system increases, the classical computational
resources required no longer increases exponentially for fixed N.
PMID- 29346967
TI - Surface contact charging.
AB - Experiments in several laboratories have demonstrated that identical materials
brought into repeated contact generate unexplained and growing surface charge
domains. Here we show that the growth of charge from these experiments can be
fitted to a previously developed first-principles model for contact charging
based on feedback of random surface polarizations. Surprisingly this mechanism,
which leads to exponential growth in colliding granular beds, can also explain
nonexponential growth of surface charging, as well as predicting spatiotemporal
growth of charge domains and their dependencies on material parameters.
PMID- 29346968
TI - Scaling behavior of thin films on chemically heterogeneous walls.
AB - We study the adsorption of a fluid in the grand canonical ensemble occurring at a
planar heterogeneous wall which is decorated with a chemical stripe of width L.
We suppose that the material of the stripe strongly preferentially adsorbs the
liquid in contrast to the outer material which is only partially wet. This
competition leads to the nucleation of a droplet of liquid on the stripe, the
height h_{m} and shape of which (at bulk two-phase coexistence) has been
predicted previously using mesoscopic interfacial Hamiltonian theory. We test
these predictions using a microscopic Fundamental Measure Density Functional
Theory which incorporates short-ranged fluid-fluid and fully long-ranged wall
fluid interactions. Our model functional accurately describes packing effects not
captured by the interfacial Hamiltonian but still we show that there is excellent
agreement with the predictions h_{m}~L^{1/2} and for the scaled circular shape of
the drop even for L as small as 50 molecular diameters. For smaller stripes the
droplet height is considerably lower than that predicted by the mesoscopic
interfacial theory. Phase transitions for droplet configurations occurring on
substrates with multiple stripes are also discussed.
PMID- 29346969
TI - Fitness voter model: Damped oscillations and anomalous consensus.
AB - We study the dynamics of opinion formation in a heterogeneous voter model on a
complete graph, in which each agent is endowed with an integer fitness parameter
k>=0, in addition to its + or - opinion state. The evolution of the distribution
of k-values and the opinion dynamics are coupled together, so as to allow the
system to dynamically develop heterogeneity and memory in a simple way. When two
agents with different opinions interact, their k-values are compared, and with
probability p the agent with the lower value adopts the opinion of the one with
the higher value, while with probability 1-p the opposite happens. The agent that
keeps its opinion (winning agent) increments its k-value by one. We study the
dynamics of the system in the entire 0<=p<=1 range and compare with the case
p=1/2, in which opinions are decoupled from the k-values and the dynamics is
equivalent to that of the standard voter model. When 0<=p<1/2, agents with higher
k-values are less persuasive, and the system approaches exponentially fast to the
consensus state of the initial majority opinion. The mean consensus time tau
appears to grow logarithmically with the number of agents N, and it is greatly
decreased relative to the linear behavior tau~N found in the standard voter
model. When 1/2 second
order -> two-stage -> first-order as the k-core threshold is increased. The
analytic equations describing the phase boundaries of the two-stage transition
region are set up, and the critical exponents for each type of transition are
derived analytically.
PMID- 29346974
TI - Additional energy-information relations in thermodynamics of small systems.
AB - The Clausius inequality form of the second law of thermodynamics relates
information changes (entropy) to changes in the first moment of the energy (heat
and indirectly also work). Are there similar relations between other moments of
the energy distribution, and other information measures, or is the Clausius
inequality a one of a kind instance of the energy-information paradigm? If there
are additional relations, can they be used to make predictions on measurable
quantities? Changes in the energy distribution beyond the first moment (average
heat or work) are especially important in small systems which are often very far
from thermal equilibrium. The additional energy-information relations (AEIR's),
here derived, provide positive answers to the two questions above and add another
layer to the fundamental connection between energy and information. To illustrate
the utility of the new AEIR's, we find scenarios where the AEIR's yield tighter
constraints on performance (e.g., in thermal machines) compared to the second
law. To obtain the AEIR's we use the Bregman divergence-a mathematical tool found
to be highly suitable for energy-information studies. The quantum version of the
AEIR's provides a thermodynamic meaning to various quantum coherence measures. It
is intriguing to fully map the regime of validity of the AEIR's and extend the
present results to more general scenarios including continuous systems and
particles exchange with the baths.
PMID- 29346975
TI - Cycle-expansion method for the Lyapunov exponent, susceptibility, and higher
moments.
AB - Lyapunov exponents characterize the chaotic nature of dynamical systems by
quantifying the growth rate of uncertainty associated with the imperfect
measurement of initial conditions. Finite-time estimates of the exponent,
however, experience fluctuations due to both the initial condition and the
stochastic nature of the dynamical path. The scale of these fluctuations is
governed by the Lyapunov susceptibility, the finiteness of which typically
provides a sufficient condition for the law of large numbers to apply. Here, we
obtain a formally exact expression for this susceptibility in terms of the Ruelle
dynamical zeta function for one-dimensional systems. We further show that, for
systems governed by sequences of random matrices, the cycle expansion of the zeta
function enables systematic computations of the Lyapunov susceptibility and of
its higher-moment generalizations. The method is here applied to a class of
dynamical models that maps to static disordered spin chains with interactions
stretching over a varying distance and is tested against Monte Carlo simulations.
PMID- 29346976
TI - Correspondence between a noisy sample-space-reducing process and records in
correlated random events.
AB - We study survival time statistics in a noisy sample-space-reducing (SSR) process.
Our simulations suggest that both the mean and standard deviation scale as
~N/N^{lambda}, where N is the system size and lambda is a tunable parameter that
characterizes the process. The survival time distribution has the form
P_{N}(tau)~N^{-theta}J(tau/N^{theta}), where J is a universal scaling function
and theta=1-lambda. Analytical insight is provided by a conjecture for the
equivalence between the survival time statistics in the noisy SSR process and the
record statistics in a correlated time series modeled as a drifted random walk
with Cauchy distributed jumps.
PMID- 29346977
TI - Dynamical ion transfer between coupled Coulomb crystals in a double-well
potential.
AB - We investigate the nonequilibrium dynamics of coupled Coulomb crystals of
different sizes trapped in a double well potential. The dynamics is induced by an
instantaneous quench of the potential barrier separating the two crystals. Due to
the intra- and intercrystal Coulomb interactions and the asymmetric population of
the potential wells, we observe a complex reordering of ions within the two
crystals as well as ion transfer processes from one well to the other. The study
and analysis of the latter processes constitutes the main focus of this work. In
particular, we examine the dependence of the observed ion transfers on the quench
amplitude performing an analysis for different crystalline configurations ranging
from one-dimensional ion chains via two-dimensional zigzag chains and ring
structures to three-dimensional spherical structures. Such an analysis provides
us with the means to extract the general principles governing the ion transfer
dynamics and we gain some insight on the structural disorder caused by the quench
of the barrier height.
PMID- 29346978
TI - Heating without heat: Thermodynamics of passive energy filters between finite
systems.
AB - Passive filters allowing the exchange of particles in a narrow band of energy are
currently used in microrefrigerators and energy transducers. In this Rapid
Communication, we analyze their thermal properties using linear irreversible
thermodynamics and kinetic theory, and discuss a striking phenomenon: the
possibility of simultaneously increasing or decreasing the temperatures of two
systems without any supply of energy. This occurs when the filter induces a flow
of particles whose energy is between the average energies of the two systems.
Here we show that this selective transfer of particles does not need the action
of any sort of Maxwell demon and can be carried out by passive filters without
compromising the second law of thermodynamics. This phenomenon allows us to
design cycles between two reservoirs at temperatures T_{1}1. And finally, for a
hyperuniform system with no long-range density fluctuations, we consider
"Einstein patterns," where each particle is independently displaced from a
lattice site by a Gaussian-distributed amount. For these, at large L,h approaches
a constant equal to about half the root-mean-square displacement in each
dimension. Then we turn to gray-scale pixel patterns that represent simulated
arrangements of polydisperse particles, where the volume of a particle is encoded
in the value of its central pixel. And we discuss the continuum limit of point
patterns, where pixel size vanishes. In general, we thus propose to quantify
particle configurations not just by the scaling of the density fluctuation
spectrum but rather by the real-space spectrum of h(L) versus L. We call this
approach "hyperuniformity disorder length spectroscopy".
PMID- 29346988
TI - Liquid part of the phase diagram and percolation line for two-dimensional
Mercedes-Benz water.
AB - Monte Carlo simulations and Wertheim's thermodynamic perturbation theory (TPT)
are used to predict the phase diagram and percolation curve for the simple two
dimensional Mercedes-Benz (MB) model of water. The MB model of water is quite
popular for explaining water properties, but the phase diagram has not been
reported till now. In the MB model, water molecules are modeled as two
dimensional Lennard-Jones disks, with three orientation-dependent hydrogen
bonding arms, arranged as in the MB logo. The liquid part of the phase space is
explored using grand canonical Monte Carlo simulations and two versions of
Wertheim's TPT for associative fluids, which have been used before to predict the
properties of the simple MB model. We find that the theory reproduces well the
physical properties of hot water but is less successful at capturing the more
structured hydrogen bonding that occurs in cold water. In addition to reporting
the phase diagram and percolation curve of the model, it is shown that the
improved TPT predicts the phase diagram rather well, while the standard one
predicts a phase transition at lower temperatures. For the percolation line, both
versions have problems predicting the correct position of the line at high
temperatures.
PMID- 29346989
TI - Generation of droplet arrays with rational number spacing patterns driven by a
periodic energy landscape.
AB - The generation of droplets at low Reynolds numbers is driven by nonlinear
dynamics that give rise to complex patterns concerning both the droplet-to
droplet spacing and the individual droplet sizes. Here we demonstrate an
experimental system in which a time-varying energy landscape provides a periodic
magnetic force that generates an array of droplets from an immiscible mixture of
ferrofluid and silicone oil. The resulting droplet patterns are periodic, owing
to the nature of the magnetic force, yet the droplet spacing and size can vary
greatly by tuning a single bias pressure applied on the ferrofluid phase; for a
given cycle period of the magnetic force, droplets can be generated either at
integer multiples (1, 2, ...), or at rational fractions (3/2, 5/3, 5/2, ...) of
this period with mono- or multidisperse droplet sizes. We develop a discrete-time
dynamical systems model not only to reproduce the phenotypes of the observed
patterns but also to provide a framework for understanding systems driven by such
periodic energy landscapes.
PMID- 29346990
TI - Critical noise can make the minority candidate win: The U.S. presidential
election cases.
AB - A national voting population, when segmented into groups such as, for example,
different states, can yield a counterintuitive scenario in which the winner may
not necessarily get the highest number of total votes. A recent example is the
2016 presidential election in the United States. We model the situation by using
interacting opinion dynamics models, and we look at the effect of coarse graining
near the critical points where the spatial fluctuations are high. We establish
that the sole effect of coarse graining, which mimics the "winner take all"
electoral college system in the United States, can give rise to finite
probabilities of events in which a minority candidate wins even in the large size
limit near the critical point. The overall probabilities of victory of the
minority candidate can be predicted from the models, which indicate that one may
expect more instances of minority candidate winning in the future.
PMID- 29346991
TI - Universal scaling of the stress-strain curve in amorphous solids.
AB - The yielding transition of amorphous solids is a phase transition with a special
type of universality. Critical exponents and scaling relations have been defined
and proposed near the yield stress. We show here that, even in the initial stage
of shear far below the yield stress, the stress-strain curve of amorphous solids
also shows critical scaling with universal exponents. The key point is to remove
the elastic part of the strain, and the shear stress exhibits a sublinear scaling
with the plastic strain. We show how this critical scaling is related to the
finite size effect of the minimum strain to trigger the first plastic avalanche
after a quench. We point out that this sublinear scaling between the stress and
the plastic strain implies the divergence of a high-order shear modulus. A
scaling relation is derived between two exponents characterizing the stress
strain curve and the density distribution of the local stabilities, respectively.
We test the critical scaling of the stress-strain curve using both mesoscopic and
atomistic simulations and get satisfying agreement in two and three dimensions.
PMID- 29346992
TI - Existence and construction of large stable food webs.
AB - Ecological diversity is ubiquitous despite the restrictions imposed by
competitive exclusion and apparent competition. To explain the observed richness
of species in a given habitat, food-web theory has explored nonlinear functional
responses, self-interaction, or spatial structure and dispersal-model ingredients
that have proven to promote stability and diversity. We return instead here to
classical Lotka-Volterra equations, where species-species interaction is
characterized by a simple product and spatial restrictions are ignored. We
quantify how this idealization imposes constraints on coexistence and diversity
for many species. To this end, we introduce the concept of free and controlled
species and use this to demonstrate how stable food webs can be constructed by
the sequential addition of species. The resulting food webs can reach dozens of
species and generally yield nonrandom degree distributions in accordance with the
constraints imposed through the assembly process. Our model thus serves as a
formal starting point for the study of sustainable interaction patterns between
species.
PMID- 29346993
TI - Vibrational resonance in an inhomogeneous medium with periodic dissipation.
AB - The role of nonlinear dissipation in vibrational resonance (VR) is investigated
in an inhomogeneous system characterized by a symmetric and spatially periodic
potential and subjected to nonuniform state-dependent damping and a biharmonic
driving force. The contributions of the parameters of the high-frequency signal
to the system's effective dissipation are examined theoretically in comparison to
linearly damped systems, for which the parameter of interest is the effective
stiffness in the equation of slow vibration. We show that the VR effect can be
enhanced by varying the nonlinear dissipation parameters and that it can be
induced by a parameter that is shared by the damping inhomogeneity and the system
potential. Furthermore, we have apparently identified the origin of the nonlinear
dissipation-enhanced response: We provide evidence of its connection to a Hopf
bifurcation, accompanied by monotonic attractor enlargement in the VR regime.
PMID- 29346994
TI - Weakly non-Boussinesq convection in a gaseous spherical shell.
AB - We examine the dynamics associated with weakly compressible convection in a
spherical shell by running 3D direct numerical simulations using the Boussinesq
formalism [Spiegel and Veronis, Astrophys. J. 131, 442 (1960)AJLEEY0004
637X10.1086/146849]. Motivated by problems in astrophysics, we assume the
existence of a finite adiabatic temperature gradient ?T_{ad} and use mixed
boundary conditions for the temperature with fixed flux at the inner boundary and
fixed temperature at the outer boundary. This setup is intrinsically more
asymmetric than the more standard case of Rayleigh-Benard convection in liquids
between parallel plates with fixed temperature boundary conditions. Conditions
where there is substantial asymmetry can cause a dramatic change in the nature of
convection and we demonstrate that this is the case here. The flows can become
pressure- rather than buoyancy-dominated, leading to anomalous heat transport by
upflows. Counterintuitively, the background temperature gradient ?T[over -] can
develop a subadiabatic layer (where g.?T[over -] resembles the spatial average in the large size limit, which
appears smooth and displays a putative elastic regime at small strains, a
yielding-related peak in stress at intermediate strain, and a plastic flow regime
at large strains. In contrast, for each glass configuration in the ensemble, the
stress-strain curve sigma(gamma) consists of many short nearly linear segments
that are punctuated by particle-rearrangement-induced rapid stress drops. To
explain the nonlinearity of , we quantify the shape of the small
stress-strain segments and the frequency and size of the stress drops in each
glass configuration. We decompose the stress loss [i.e., the deviation in the
slope of from that at ] into the loss from particle
rearrangements and the loss from softening [i.e., the reduction of the slopes of
the linear segments in sigma(gamma)], and then compare the two contributions as a
function of R and gamma. For the current studies, the rearrangement-induced
stress loss is larger than the softening-induced stress loss, however, softening
stress losses increase with decreasing cooling rate. We also characterize the
structure of the potential energy landscape along the strain direction for
glasses prepared with different R, and observe a dramatic change of the
properties of the landscape near the yielding transition. We then show that the
rearrangement-induced energy loss per strain can serve as an order parameter for
the yielding transition, which sharpens for slow cooling rates and in large
systems.
PMID- 29346997
TI - Deformation and buckling of microcapsules in a viscoelastic matrix.
AB - In this paper, we numerically study the dynamics of (1) a Newtonian liquid-filled
capsule in a viscoelastic matrix and that of (2) a viscoelastic capsule in a
Newtonian matrix in a linear shear flow using a front-tracking method. The
numerical results for case (1) indicate that the polymeric fluid reduces the
capsule deformation and aligns the deformed capsule with the flow direction. It
also narrows the range of tension experienced by the deformed capsule for case
(1), while the tank-treading period significantly increases. Interestingly, the
polymeric fluid has an opposite effect on the tank-treading period and the
orientation angle of case (2), but its effect on the deformation is similar to
case (1).
PMID- 29346998
TI - Antiferromagnetic Ising model in an imaginary magnetic field.
AB - We study the two-dimensional antiferromagnetic Ising model with a purely
imaginary magnetic field, which can be thought of as a toy model for the usual
theta physics. Our motivation is to have a benchmark calculation in a system
which suffers from a strong sign problem, so that our results can be used to test
Monte Carlo methods developed to tackle such problems. We analyze here this model
by means of analytical techniques, computing exactly the first eight cumulants of
the expansion of the effective Hamiltonian in powers of the inverse temperature,
and calculating physical observables for a large number of degrees of freedom
with the help of standard multiprecision algorithms. We report accurate results
for the free energy density, internal energy, standard and staggered
magnetization, and the position and nature of the critical line, which confirm
the mean-field qualitative picture, and which should be quantitatively reliable,
at least in the high-temperature regime, including the entire critical line.
PMID- 29346999
TI - Mean flow produced by small-amplitude vibrations of a liquid bridge with its free
surface covered with an insoluble surfactant.
AB - As is well known, confined fluid systems subject to forced vibrations produce
mean flows, called in this context streaming flows. These mean flows promote an
overall mass transport in the fluid that has consequences in the transport of
passive scalars and surfactants, when these are present in a fluid interface.
Such transport causes surfactant concentration inhomogeneities that are to be
counterbalanced by Marangoni elasticity. Therefore, the interaction of streaming
flows and Marangoni convection is expected to produce new flow structures that
are different from those resulting when only one of these effects is present. The
present paper focuses on this interaction using the liquid bridge geometry as a
paradigmatic system for the analysis. Such analysis is based on an appropriate
post-processing of the results obtained via direct numerical simulation of the
system for moderately small viscosity, a condition consistent with typical
experiments of vibrated millimetric liquid bridges. It is seen that the flow
patterns show a nonmonotone behavior as the Marangoni number is increased. In
addition, the strength of the mean flow at the free surface exhibits two well
defined regimes as the forcing amplitude increases. These regimes show fairly
universal power-law behaviors.
PMID- 29347000
TI - Pattern production through a chiral chasing mechanism.
AB - Recent experiments on zebrafish pigmentation suggests that their typical black
and white striped skin pattern is made up of a number of interacting
chromatophore families. Specifically, two of these cell families have been shown
to interact through a nonlocal chasing mechanism, which has previously been
modeled using integro-differential equations. We extend this framework to include
the experimentally observed fact that the cells often exhibit chiral movement, in
that the cells chase, and run away, at angles different to the line connecting
their centers. This framework is simplified through the use of multiple small
limits leading to a coupled set of partial differential equations which are
amenable to Fourier analysis. This analysis results in the production of
dispersion relations and necessary conditions for a patterning instability to
occur. Beyond the theoretical development and the production of new pattern
planiforms we are able to corroborate the experimental hypothesis that the global
pigmentation patterns can be dependent on the chirality of the chromatophores.
PMID- 29347001
TI - Universal scaling of the distribution of land in urban areas.
AB - In this work, we explore the spatial structure of built zones and green areas in
diverse western cities by analyzing the probability distribution of areas and a
coefficient that characterize their respective shapes. From the analysis of
diverse datasets describing land lots in urban areas, we found that the
distribution of built-up areas and natural zones in cities obey inverse power
laws with a similar scaling for the cities explored. On the other hand, by
studying the distribution of shapes of lots in urban regions, we are able to
detect global differences in the spatial structure of the distribution of land.
Our findings introduce information about spatial patterns that emerge in the
structure of urban settlements; this knowledge is useful for the understanding of
urban growth, to improve existing models of cities, in the context of
sustainability, in studies about human mobility in urban areas, among other
applications.
PMID- 29347002
TI - Work and power fluctuations in a critical heat engine.
AB - We investigate fluctuations of output work for a class of Stirling heat engines
with working fluid composed of interacting units and compare these fluctuations
to an average work output. In particular, we focus on engine performance close to
a critical point where Carnot's efficiency may be attained at a finite power as
reported by M. Campisi and R. Fazio [Nat. Commun. 7, 11895 (2016)2041
172310.1038/ncomms11895]. We show that the variance of work output per cycle
scales with the same critical exponent as the heat capacity of the working fluid.
As a consequence, the relative work fluctuation diverges unless the output work
obeys a rather strict scaling condition, which would be very hard to fulfill in
practice. Even under this condition, the fluctuations of work and power do not
vanish in the infinite system size limit. Large fluctuations of output work thus
constitute inseparable and dominant element in performance of the macroscopic
heat engines close to a critical point.
PMID- 29347003
TI - Killing (absorption) versus survival in random motion.
AB - We address diffusion processes in a bounded domain, while focusing on somewhat
unexplored affinities between the presence of absorbing and/or inaccessible
boundaries. For the Brownian motion (Levy-stable cases are briefly mentioned)
model-independent features are established of the dynamical law that underlies
the short-time behavior of these random paths, whose overall lifetime is
predefined to be long. As a by-product, the limiting regime of a permanent
trapping in a domain is obtained. We demonstrate that the adopted conditioning
method, involving the so-called Bernstein transition function, works properly
also in an unbounded domain, for stochastic processes with killing (Feynman-Kac
kernels play the role of transition densities), provided the spectrum of the
related semigroup operator is discrete. The method is shown to be useful in the
case, when the spectrum of the generator goes down to zero and no isolated
minimal (ground state) eigenvalue is in existence, like in the problem of the
long-term survival on a half-line with a sink at origin.
PMID- 29347004
TI - Self-propulsion against a moving membrane: Enhanced accumulation and drag force.
AB - Self-propulsion (SP) is a main feature of active particles (AP), such as bacteria
or biological micromotors, distinguishing them from passive colloids. A renowned
consequence of SP is accumulation at static interfaces, even in the absence of
hydrodynamic interactions. Here we address the role of SP in the interaction
between AP and a moving semipermeable membrane. In particular, we implement a
model of noninteracting AP in a channel crossed by a partially penetrable wall,
moving at a constant velocity c. With respect to both the cases of passive
colloids with c>0 and AP with c=0, the AP with finite c show enhancement of
accumulation in front of the obstacle and experience a largely increased drag
force. This effect is understood in terms of an effective potential localised at
the interface between particles and membrane, of height proportional to ctau/xi,
where tau is the AP's reorientation time and xi the width characterizing the
surface's smoothness (xi->0 for hard core obstacles). An approximate analytical
scheme is able to reproduce the observed density profiles and the measured drag
force, in very good agreement with numerical simulations. The effects discussed
here can be exploited for automatic selection and filtering of AP with desired
parameters.
PMID- 29347005
TI - Universality-class crossover by a nonorder field introduced to the pair contact
process with diffusion.
AB - The one-dimensional pair contact process with diffusion (PCPD), an interacting
particle system with diffusion, pair annihilation, and creation by pairs, has
defied consensus about the universality class to which it belongs. An argument by
Hinrichsen [Physica A 361, 457 (2006)PHYADX0378-437110.1016/j.physa.2005.06.101]
claims that freely diffusing particles in the PCPD should play the same role as
frozen particles when it comes to the critical behavior. Therefore, the PCPD is
claimed to have the same critical phenomena as a model with infinitely many
absorbing states that belongs to the directed percolation (DP) universality
class. To investigate if diffusing particles are really indistinguishable from
frozen particles in the sense of the renormalization group, we study numerically
a variation of the PCPD by introducing a nonorder field associated with
infinitely many absorbing states. We find that a crossover from the PCPD to DP
occurs due to the nonorder field. By studying a similar model, we exclude the
possibility that the mere introduction of a nonorder field to one model can
entail a nontrivial crossover to another model in the same universality class,
thus we attribute the observed crossover to the difference of the universality
class of the PCPD from the DP class.
PMID- 29347006
TI - Two-time correlation functions and the Lee-Yang zeros for an interacting Bose
gas.
AB - Two-time correlation functions of a system of Bose particles are studied. We find
a relation of zeros of the correlation functions with the Lee-Yang zeros of the
partition function of the system. The obtained relation gives the possibility to
observe the Lee-Yang zeros experimentally. A particular case of Bose particles on
two levels is examined, and zeros of two-time correlation functions and Lee-Yang
zeros of the partition function of the system are analyzed.
PMID- 29347007
TI - Critical transitions and perturbation growth directions.
AB - Critical transitions occur in a variety of dynamical systems. Here we employ
quantifiers of chaos to identify changes in the dynamical structure of complex
systems preceding critical transitions. As suitable indicator variables for
critical transitions, we consider changes in growth rates and directions of
covariant Lyapunov vectors. Studying critical transitions in several models of
fast-slow systems, i.e., a network of coupled FitzHugh-Nagumo oscillators, models
for Josephson junctions, and the Hindmarsh-Rose model, we find that tangencies
between covariant Lyapunov vectors are a common and maybe generic feature during
critical transitions. We further demonstrate that this deviation from hyperbolic
dynamics is linked to the occurrence of critical transitions by using it as an
indicator variable and evaluating the prediction success through receiver
operating characteristic curves. In the presence of noise, we find the alignment
of covariant Lyapunov vectors and changes in finite-time Lyapunov exponents to be
more successful in announcing critical transitions than common indicator
variables as, e.g., finite-time estimates of the variance. Additionally, we
propose a new method for estimating approximations of covariant Lyapunov vectors
without knowledge of the future trajectory of the system. We find that these
approximated covariant Lyapunov vectors can also be applied to predict critical
transitions.
PMID- 29347008
TI - Erratum: Correlations in suspensions confined between viscoelastic surfaces:
Noncontact microrheology [Phys. Rev. E 96, 022607 (2017)].
AB - This corrects the article DOI: 10.1103/PhysRevE.96.022607.
PMID- 29347009
TI - Evolutionary stability concepts in a stochastic environment.
AB - Over the past 30 years, evolutionary game theory and the concept of an
evolutionarily stable strategy have been not only extensively developed and
successfully applied to explain the evolution of animal behaviors, but also
widely used in economics and social sciences. Nonetheless, the stochastic
dynamical properties of evolutionary games in randomly fluctuating environments
are still unclear. In this study, we investigate conditions for stochastic local
stability of fixation states and constant interior equilibria in a two-phenotype
model with random payoffs following pairwise interactions. Based on this model,
we develop the concepts of stochastic evolutionary stability (SES) and stochastic
convergence stability (SCS). We show that the condition for a pure strategy to be
SES and SCS is more stringent than in a constant environment, while the condition
for a constant mixed strategy to be SES is less stringent than the condition to
be SCS, which is less stringent than the condition in a constant environment.
PMID- 29347010
TI - Erratum: Optimization of finite-size errors in finite-temperature calculations of
unordered phases [Phys. Rev. E 91, 062142 (2015)].
AB - This corrects the article DOI: 10.1103/PhysRevE.91.062142.
PMID- 29347011
TI - Luminescence from cavitation bubbles deformed in uniform pressure gradients.
AB - Presented here are observations that demonstrate how the deformation of
millimetric cavitation bubbles by a uniform pressure gradient quenches single
collapse luminescence. Our innovative measurement system captures a broad
luminescence spectrum (wavelength range, 300-900 nm) from the individual
collapses of laser-induced bubbles in water. By varying the bubble size, driving
pressure, and perceived gravity level aboard parabolic flights, we probed the
limit from aspherical to highly spherical bubble collapses. Luminescence was
detected for bubbles of maximum radii within the previously uncovered range,
R_{0}=1.5-6 mm, for laser-induced bubbles. The relative luminescence energy was
found to rapidly decrease as a function of the bubble asymmetry quantified by the
anisotropy parameter zeta, which is the dimensionless equivalent of the Kelvin
impulse. As established previously, zeta also dictates the characteristic
parameters of bubble-driven microjets. The threshold of zeta beyond which no
luminescence is observed in our experiment closely coincides with the threshold
where the microjets visibly pierce the bubble and drive a vapor jet during the
rebound. The individual fitted blackbody temperatures range between T_{lum}=7000
and T_{lum}=11500 K but do not show any clear trend as a function of zeta. Time
resolved measurements using a high-speed photodetector disclose multiple
luminescence events at each bubble collapse. The averaged full width at half
maximum of the pulse is found to scale with R_{0} and to range between 10 and 20
ns.
PMID- 29347012
TI - Steady diffusion in a drift field: A comparison of large-deviation techniques and
multiple-scale analysis.
AB - A particle with internal unobserved states diffusing in a force field will
generally display effective advection-diffusion. The drift velocity is
proportional to the mobility averaged over the internal states, or effective
mobility, while the effective diffusion has two terms. One is of the equilibrium
type and satisfies an Einstein relation with the effective mobility while the
other is quadratic in the applied force. In this contribution we present two new
methods to obtain these results, on the one hand using large deviation techniques
and on the other by a multiple-scale analysis, and compare the two. We consider
both systems with discrete internal states and continuous internal states. We
show that the auxiliary equations in the multiple-scale analysis can also be
derived in second-order perturbation theory in a large deviation theory of a
generating function (discrete internal states) or generating functional
(continuous internal states). We discuss that measuring the two components of the
effective diffusion give a way to determine kinetic rates from only first and
second moments of the displacement in steady state.
PMID- 29347013
TI - Correlations in magnitude series to assess nonlinearities: Application to
multifractal models and heartbeat fluctuations.
AB - The correlation properties of the magnitude of a time series are associated with
nonlinear and multifractal properties and have been applied in a great variety of
fields. Here we have obtained the analytical expression of the autocorrelation of
the magnitude series (C_{|x|}) of a linear Gaussian noise as a function of its
autocorrelation (C_{x}). For both, models and natural signals, the deviation of
C_{|x|} from its expectation in linear Gaussian noises can be used as an index of
nonlinearity that can be applied to relatively short records and does not require
the presence of scaling in the time series under study. In a model of artificial
Gaussian multifractal signal we use this approach to analyze the relation between
nonlinearity and multifractallity and show that the former implies the latter but
the reverse is not true. We also apply this approach to analyze experimental
data: heart-beat records during rest and moderate exercise. For each individual
subject, we observe higher nonlinearities during rest. This behavior is also
achieved on average for the analyzed set of 10 semiprofessional soccer players.
This result agrees with the fact that other measures of complexity are
dramatically reduced during exercise and can shed light on its relationship with
the withdrawal of parasympathetic tone and/or the activation of sympathetic
activity during physical activity.
PMID- 29347014
TI - Imperfections, impacts, and the singularity of Euler's disk.
AB - The motion of a rigid, spinning disk on a flat surface ends with a dissipation
induced finite-time singularity. The problem of finding the dominant energy
absorption mechanism during the last phase of the motion generated a lively
debate during the past two decades. Various candidates including air drag and
different types of friction have been considered, nevertheless impacts have not
been examined until now. We investigate the effect of impacts caused by geometric
imperfections of the disk and of the underlying flat surface, through analyzing
the dynamics of polygonal disks with unilateral point contacts. Similarly to
earlier works, we determine the rate of energy absorption under the assumption of
a regular pattern of motion analogous to precession-free motion of a rolling
disk. In addition, we demonstrate that the asymptotic stability of this motion
depends on parameters of the impact model. In the case of instability, the
emerging irregular motion is investigated numerically. We conclude that there
exists a range of model parameters (small radii of gyration or small restitution
coefficients) in which absorption by impacts dominates all previously
investigated mechanisms during the last phase of motion. Nevertheless the
parameter values associated with a homogeneous disk on a hard surface are
typically not in this range, hence the effect of impacts is in that case not
dominant.
PMID- 29347015
TI - Mathematical and information-geometrical entropy for phenomenological Fourier and
non-Fourier heat conduction.
AB - The second law of thermodynamics governs the direction of heat transport, which
provides the foundational definition of thermodynamic Clausius entropy. The
definitions of entropy are further generalized for the phenomenological heat
transport models in the frameworks of classical irreversible thermodynamics and
extended irreversible thermodynamics (EIT). In this work, entropic functions from
mathematics are combined with phenomenological heat conduction models and
connected to several information-geometrical conceptions. The long-time behaviors
of these mathematical entropies exhibit a wide diversity and physical pictures in
phenomenological heat conductions, including the tendency to thermal equilibrium,
and exponential decay of nonequilibrium and asymptotics, which build a bridge
between the macroscopic and microscopic modelings. In contrast with the EIT
entropies, the mathematical entropies expressed in terms of the internal energy
function can avoid singularity paired with nonpositive local absolute temperature
caused by non-Fourier heat conduction models.
PMID- 29347016
TI - Modeling a photoinduced planar-to-homeotropic anchoring transition triggered by
surface azobenzene units in a nematic liquid crystal.
AB - The performance of light-controlled liquid crystal anchoring surfaces depends on
the nature of the photosensitive moieties and on the concentration of spacer
units. Here, we study the kinetics of photosensitive liquid crystal cells that
incorporate an azobenzene-based self-assembled monolayer. We characterize the
photoinduced homeotropic-to-planar transition and the subsequent reverse
relaxation in terms of the underlying isomerization of the photosensitive layer.
We show that the response time can be precisely adjusted by tuning the lateral
packing of azobenzene units by means of inert spacer molecules. Using simple
kinetic assumptions and a well-known model for the energetics of liquid crystal
anchoring we are able to capture the details of the optical microscopy
experimental observations. Our analysis provides fitted values for all the
relevant material parameters, including the zenithal and the azimuthal anchoring
strength.
PMID- 29347017
TI - Friction force regimes and the conditions for endless penetration of an intruder
into a granular medium.
AB - An intruder penetrating into a granular column experiences a depth-dependent
friction force F(z). Different regimes of F(z) have been measured depending on
the experimental design: a nearly linear dependence for shallow penetrations,
total saturation at large depths, and an exponential increase when the intruder
approaches the bottom of the granular bed. We report here an experiment that
allows us to measure the different regimes in a single run during the quasistatic
descent of a sphere in a light granular medium. From the analysis of the
resistance in the saturation zone, it was found that F(z) follows a cube-power
law dependence on the intruder diameter and an exponential increase with the
packing fraction of the bed. Moreover, we determine the critical mass m_{c}
required to observe infinite penetration and its dependence on the above
parameters. Finally, we use our results to estimate the final penetration depth
reached by intruders of masses m0^{+}, which displays a nontrivial
behavior with the strength of disorder R. We verify our predictions with
numerical simulations. In the second part of the paper, motivated by avalanche
gap distributions in driven disordered amorphous solids, we study a long-range
antiferromagnetic RFIM. This model displays a gapped behavior P(DeltaH)=0 up to a
system size dependent offset value DeltaH_{off}, and P(DeltaH)~(DeltaH
DeltaH_{off})^{theta} as DeltaH->H_{off}^{+}. We perform numerical simulations on
this model and determine theta~0.95(5). We also discuss mechanisms which would
lead to a nonzero exponent theta for general spin models with quenched random
fields.
PMID- 29347022
TI - Destabilization of a liquid metal by nonuniform Joule heating.
AB - We study the effect of an impressing AC magnetic field at the bottom of a liquid
metal layer of thickness h. In this situation the fluid is set in motion by the
buoyancy forces caused by internal heat sources. The heat sources, caused by the
Joule effect induced by the AC field, present an exponentially decaying profile,
with characteristic length delta. As the magnetic field is horizontal, the
Lorentz force has no influence on the dynamics of the system since it contributes
only to the magnetic pressure. We propose an analysis of both the transient and
fully developed regimes using linear stability analysis (LSA) and direct
numerical simulations (DNSs). The transient period is governed by the temporal
evolution of the temperature field as well as the development of the convective
instability, which can be concomitant and therefore requires adopting a transient
LSA algorithm to track these two effects. The DNSs have been performed for
various distributions of the heat sources and various total heat input. This
corresponds to independently varying delta/h in the range 0.04<=delta/h<=0.45 and
a Rayleigh number 1.1*10^{4}<=Ra<=1.2*10^{5}. We observe the relaxation of the
temperature up to the steady conductive profile before the transition to the
nonlinear regime when Ra is small, whereas for larger Ra, nonlinear effects
appear during the relaxation of the temperature profile. The unsteadiness of the
temperature field significantly alters the development of the instability because
of a much smaller growth rate. Surprisingly, we observe that delta/h has only a
limited influence on averaged quantities as well as on the patterns for both the
linear and nonlinear regimes. This comes with the fact that the profiles present
an apparent reflectional symmetry, despite the asymmetry of the governing
equations.
PMID- 29347023
TI - Stability of the quantum Sherrington-Kirkpatrick spin glass model.
AB - I study in detail the quantum Sherrington-Kirkpatrick (SK) model, i.e., the
infinite-range Ising spin glass in a transverse field, by solving numerically the
effective one-dimensional model that the quantum SK model can be mapped to in the
thermodynamic limit. I find that the replica symmetric solution is unstable down
to zero temperature, in contrast to some previous claims, and so there is not
only a line of transitions in the (longitudinal) field-temperature plane (the de
Almeida-Thouless, AT, line) where replica symmetry is broken, but also a quantum
de Almeida-Thouless (QuAT) line in the transverse field-longitudinal field plane
at T=0. If the QuAT line also occurs in models with short-range interactions its
presence might affect the performance of quantum annealers when solving spin
glass-type problems with a bias (i.e., magnetic field).
PMID- 29347024
TI - Dimensionless embedding for nonlinear time series analysis.
AB - Recently, infinite-dimensional delay coordinates (InDDeCs) have been proposed for
predicting high-dimensional dynamics instead of conventional delay coordinates.
Although InDDeCs can realize faster computation and more accurate short-term
prediction, it is still not well-known whether InDDeCs can be used in other
applications of nonlinear time series analysis in which reconstruction is needed
for the underlying dynamics from a scalar time series generated from a dynamical
system. Here, we give theoretical support for justifying the use of InDDeCs and
provide numerical examples to show that InDDeCs can be used for various
applications for obtaining the recurrence plots, correlation dimensions, and
maximal Lyapunov exponents, as well as testing directional couplings and
extracting slow-driving forces. We demonstrate performance of the InDDeCs using
the weather data. Thus, InDDeCs can eventually realize "dimensionless embedding"
while we enjoy faster and more reliable computations.
PMID- 29347025
TI - Distribution of shortest path lengths in a class of node duplication network
models.
AB - We present analytical results for the distribution of shortest path lengths
(DSPL) in a network growth model which evolves by node duplication (ND). The
model captures essential properties of the structure and growth dynamics of
social networks, acquaintance networks, and scientific citation networks, where
duplication mechanisms play a major role. Starting from an initial seed network,
at each time step a random node, referred to as a mother node, is selected for
duplication. Its daughter node is added to the network, forming a link to the
mother node, and with probability p to each one of its neighbors. The degree
distribution of the resulting network turns out to follow a power-law
distribution, thus the ND network is a scale-free network. To calculate the DSPL
we derive a master equation for the time evolution of the probability P_{t}(L=l),
l=1,2,?, where L is the distance between a pair of nodes and t is the time.
Finding an exact analytical solution of the master equation, we obtain a closed
form expression for P_{t}(L=l). The mean distance _{t} and the diameter
Delta_{t} are found to scale like lnt, namely, the ND network is a small-world
network. The variance of the DSPL is also found to scale like lnt. Interestingly,
the mean distance and the diameter exhibit properties of a small-world network,
rather than the ultrasmall-world network behavior observed in other scale-free
networks, in which _{t}~lnlnt.
PMID- 29347026
TI - Analytical theory of the hydrophobic effect of solutes in water.
AB - We develop an analytical statistical-mechanical model for hydrophobic solvation
in water. In this three-dimensional Mercedes-Benz-like model, two neighboring
waters have three possible interaction states: a radial van der Waals
interaction, a tetrahedral orientation-dependent hydrogen-bonding interaction, or
no interaction. Nonpolar solutes are modeled as van der Waals particles of
different radii. The model is sufficiently simple that we can calculate the
partition function and thermal and volumetric properties of solvation versus
temperature, pressure, and solute radius. Predictions are in good agreement with
results of Monte Carlo simulations. And their trends agree with experiments on
hydrophobic solute insertion. The theory shows that first-shell waters are more
highly structured than bulk waters, because of hydrogen bonding, and that that
structure melts out faster with temperature than it does in bulk waters. Because
the theory is analytical, it can explore a broad range of solvation properties
and anomalies of water, at minimal computational expense.
PMID- 29347027
TI - Thermal gas rectification using a sawtooth channel.
AB - We study the rectification of a two-dimensional thermal gas in a channel of
asymmetric dissipative walls. For an ensemble of smooth Lennard-Jones particles,
our numerical simulations reveal a nonmonotonic dependence of the flux on the
thermostat temperature, channel asymmetry, and particle density, with three
distinct regimes. Theoretical arguments are developed to shed light on the
functional dependence of the flux on the model parameters.
PMID- 29347028
TI - Continuous-time random-walk model for anomalous diffusion in expanding media.
AB - Expanding media are typical in many different fields, e.g., in biology and
cosmology. In general, a medium expansion (contraction) brings about dramatic
changes in the behavior of diffusive transport properties such as the set of
positional moments and the Green's function. Here, we focus on the
characterization of such effects when the diffusion process is described by the
continuous-time random-walk (CTRW) model. As is well known, when the medium is
static this model yields anomalous diffusion for a proper choice of the
probability density function (pdf) for the jump length and the waiting time, but
the behavior may change drastically if a medium expansion is superimposed on the
intrinsic random motion of the diffusing particle. For the case where the jump
length and the waiting time pdfs are long-tailed, we derive a general
bifractional diffusion equation which reduces to a normal diffusion equation in
the appropriate limit. We then study some particular cases of interest, including
Levy flights and subdiffusive CTRWs. In the former case, we find an analytical
exact solution for the Green's function (propagator). When the expansion is
sufficiently fast, the contribution of the diffusive transport becomes irrelevant
at long times and the propagator tends to a stationary profile in the comoving
reference frame. In contrast, for a contracting medium a competition between the
spreading effect of diffusion and the concentrating effect of contraction arises.
In the specific case of a subdiffusive CTRW in an exponentially contracting
medium, the latter effect prevails for sufficiently long times, and all the
particles are eventually localized at a single point in physical space. This "big
crunch" effect, totally absent in the case of normal diffusion, stems from
inefficient particle spreading due to subdiffusion. We also derive a hierarchy of
differential equations for the moments of the transport process described by the
subdiffusive CTRW model in an expanding medium. From this hierarchy, the full
time evolution of the second-order moment is obtained for some specific types of
expansion. In the case of an exponential expansion, exact recurrence relations
for the Laplace-transformed moments are obtained, whence the long-time behavior
of moments of arbitrary order is subsequently inferred. Our analytical and
numerical results for both Levy flights and subdiffusive CTRWs confirm the
intuitive expectation that the medium expansion hinders the mixing of diffusive
particles occupying separate regions. In the case of Levy flights, we quantify
this effect by means of the so-called "Levy horizon."
PMID- 29347029
TI - Transient chaos and associated system-intrinsic switching of spacetime patterns
in two synaptically coupled layers of Morris-Lecar neurons.
AB - Spatiotemporal chaos collapses to either a rest state or a propagating pulse
solution in a single layer of diffusively coupled, excitable Morris-Lecar
neurons. Weak synaptic coupling of two such layers reveals system intrinsic
switching of spatiotemporal activity patterns within and between the layers at
irregular times. Within a layer, switching sequences include spatiotemporal
chaos, erratic and regular pulse propagation, spontaneous network wide neuron
activity, and rest state. A momentary substantial reduction in neuron activity in
one layer can reinitiate transient spatiotemporal chaos in the other layer, which
can induce a swap of spatiotemporal chaos with a pulse state between the layers.
Presynaptic input maximizes the distance between propagating pulses, in contrast
to pulse merging in the absence of synapses.
PMID- 29347030
TI - Phase diagrams for sticky rods in bulk and in a monolayer from a lattice free
energy functional for anisotropic particles with depletion attractions.
AB - A density functional of fundamental measure type for a lattice model of
anisotropic particles with hard-core repulsions and effective attractions is
derived in the spirit of the Asakura-Oosawa model. Through polymeric lattice
particles of various size and shape, effective attractions of different strength
and range between the colloids can be generated. The functional is applied to the
determination of phase diagrams for sticky rods of length L in two dimensions, in
three dimensions, and in a monolayer system on a neutral substrate. In all cases,
there is a competition between ordering and gas-liquid transitions. In two
dimensions, this gives rise to a tricritical point, whereas in three dimensions,
the isotropic-nematic transition crosses over smoothly to a gas-nematic liquid
transition. The richest phase behavior is found for the monolayer system. For
L=2, two stable critical points are found corresponding to a standard gas-liquid
transition and a nematic liquid-liquid transition. For L=3, the gas-liquid
transition becomes metastable.
PMID- 29347031
TI - Fractality in nonequilibrium steady states of quasiperiodic systems.
AB - We investigate the nonequilibrium response of quasiperiodic systems to boundary
driving. In particular, we focus on the Aubry-Andre-Harper model at its metal
insulator transition and the diagonal Fibonacci model. We find that opening the
system at the boundaries provides a viable experimental technique to probe its
underlying fractality, which is reflected in the fractal spatial dependence of
simple observables (such as magnetization) in the nonequilibrium steady state. We
also find that the dynamics in the nonequilibrium steady state depends on the
length of the chain chosen: generic length chains harbour qualitatively slower
transport (different scaling exponent) than Fibonacci length chains, which is in
turn slower than in the closed system. We conjecture that such fractal
nonequilibrium steady states should arise in generic driven critical systems that
have fractal properties.
PMID- 29347032
TI - Subspace dynamic mode decomposition for stochastic Koopman analysis.
AB - The analysis of nonlinear dynamical systems based on the Koopman operator is
attracting attention in various applications. Dynamic mode decomposition (DMD) is
a data-driven algorithm for Koopman spectral analysis, and several variants with
a wide range of applications have been proposed. However, popular implementations
of DMD suffer from observation noise on random dynamical systems and generate
inaccurate estimation of the spectra of the stochastic Koopman operator. In this
paper, we propose subspace DMD as an algorithm for the Koopman analysis of random
dynamical systems with observation noise. Subspace DMD first computes the
orthogonal projection of future snapshots to the space of past snapshots and then
estimates the spectra of a linear model, and its output converges to the spectra
of the stochastic Koopman operator under standard assumptions. We investigate the
empirical performance of subspace DMD with several dynamical systems and show its
utility for the Koopman analysis of random dynamical systems.
PMID- 29347033
TI - Basins of attraction of the bistable region of time-delayed cutting dynamics.
AB - This paper investigates the effects of bistability in a nonsmooth time-delayed
dynamical system, which is often manifested in science and engineering. Previous
studies on cutting dynamics have demonstrated persistent coexistence of chatter
and chatter-free responses in a bistable region located in the linearly stable
zone. As there is no widely accepted definition of basins of attraction for time
delayed systems, bistable regions are coined as unsafe zones (UZs). Hence, we
have attempted to define the basins of attraction and stability basins for a
typical delayed system to get insight into the bistability in systems with time
delays. Special attention was paid to the influences of delayed initial
conditions, starting points, and states at time zero on the long-term dynamics of
time-delayed systems. By using this concept, it has been confirmed that the
chatter is prone to occur when the waviness frequency in the workpiece surface
coincides with the effective natural frequency of the cutting process. Further
investigations unveil a thin "boundary layer" inside the UZ in the immediate
vicinity of the stability boundary, in which we observe an extremely fast growth
of the chatter basin stability. The results reveal that the system is more stable
when the initial cutting depth is smaller. The physics of the tool deflection at
the instant of the tool-workpiece engagement is used to evaluate the cutting
safety, and the safe level could be zero when the geometry of tool engagement is
unfavorable. Finally, the basins of attraction are used to quench the chatter by
a single strike, where the resultant "islands" offer an opportunity to suppress
the chatter even when the cutting is very close to the stability boundary.
PMID- 29347034
TI - Power-law citation distributions are not scale-free.
AB - We analyze time evolution of statistical distributions of citations to scientific
papers published in the same year. While these distributions seem to follow the
power-law dependence we find that they are nonstationary and the exponent of the
power-law fit decreases with time and does not come to saturation. We attribute
the nonstationarity of citation distributions to different longevity of the low
cited and highly cited papers. By measuring citation trajectories of papers we
found that citation careers of the low-cited papers come to saturation after 10
15 years while those of the highly cited papers continue to increase
indefinitely: The papers that exceed some citation threshold become runaways.
Thus, we show that although citation distribution can look as a power-law
dependence, it is not scale free and there is a hidden dynamic scale associated
with the onset of runaways. We compare our measurements to our recently developed
model of citation dynamics based on copying-redirection-triadic closure and find
explanations to our empirical observations.
PMID- 29347035
TI - Aging transition in systems of oscillators with global distributed-delay
coupling.
AB - We consider a globally coupled network of active (oscillatory) and inactive
(nonoscillatory) oscillators with distributed-delay coupling. Conditions for
aging transition, associated with suppression of oscillations, are derived for
uniform and gamma delay distributions in terms of coupling parameters and the
proportion of inactive oscillators. The results suggest that for the uniform
distribution increasing the width of distribution for the same mean delay allows
aging transition to happen for a smaller coupling strength and a smaller
proportion of inactive elements. For gamma distribution with sufficiently large
mean time delay, it may be possible to achieve aging transition for an arbitrary
proportion of inactive oscillators, as long as the coupling strength lies in a
certain range.
PMID- 29347036
TI - Front propagation in weakly subcritical pattern-forming systems.
AB - The speed and stability of fronts near a weakly subcritical steady-state
bifurcation are studied, focusing on the transition between pushed and pulled
fronts in the bistable Ginzburg-Landau equation. Exact nonlinear front solutions
are constructed and their stability properties investigated. In some cases, the
exact solutions are stable but are not selected from arbitrary small amplitude
initial conditions. In other cases, the exact solution is unstable to
modulational instabilities which select a distinct front. Chaotic front dynamics
may result and is studied using numerical techniques.
PMID- 29347037
TI - Escape of coupled Brownian particles across a fluctuating barrier.
AB - The escape of two harmonically coupled Brownian particles across the fluctuating
barrier of a bistable potential is investigated with correlated additive and
multiplicative fluctuations. Positive correlations enhance the rate of escape
across the barrier when the coupling is effective, whereas for weakly coupled
particles, escape becomes difficult. It is found that the system exhibits the
phenomenon of resonant activation when the rate of barrier fluctuations is
comparable to the relaxation time in the bistable potential. Using a decoupling
ansatz, we derive the Markovian limit of the problem in the steady state, under
the constraint that the barriers fluctuate on a time scale faster than the
relative oscillation of the two particles. Adiabatic elimination of the fast
variable of the dynamical system is discussed in appropriate limits.
PMID- 29347038
TI - Shock propagation in locally driven granular systems.
AB - We study shock propagation in a system of initially stationary hard spheres that
is driven by a continuous injection of particles at the origin. The disturbance
created by the injection of energy spreads radially outward through collisions
between particles. Using scaling arguments, we determine the exponent
characterizing the power-law growth of this disturbance in all dimensions. The
scaling functions describing the various physical quantities are determined using
large-scale event-driven simulations in two and three dimensions for both elastic
and inelastic systems. The results are shown to describe well the data from two
different experiments on granular systems that are similarly driven.
PMID- 29347039
TI - Recurrence relations in one-dimensional Ising models.
AB - The exact finite-size partition function for the nonhomogeneous one-dimensional
(1D) Ising model is found through an approach using algebra operators.
Specifically, in this paper we show that the partition function can be computed
through a trace from a linear second-order recurrence relation with nonconstant
coefficients in matrix form. A relation between the finite-size partition
function and the generalized Lucas polynomials is found for the simple
homogeneous model, thus establishing a recursive formula for the partition
function. This is an important property and it might indicate the possible
existence of recurrence relations in higher-dimensional Ising models. Moreover,
assuming quenched disorder for the interactions within the model, the quenched
averaged magnetic susceptibility displays a nontrivial behavior due to changes in
the ferromagnetic concentration probability.
PMID- 29347040
TI - Electrical autonomous Brownian gyrator.
AB - We study experimentally and theoretically the steady-state dynamics of a simple
stochastic electronic system featuring two resistor-capacitor circuits coupled by
a third capacitor. The resistors are subject to thermal noises at real
temperatures. The voltage fluctuation across each resistor can be compared to a
one-dimensional Brownian motion. However, the collective dynamical behavior, when
the resistors are subject to distinct thermal baths, is identical to that of a
Brownian gyrator, as first proposed by Filliger and Reimann [Phys. Rev. Lett. 99,
230602 (2007)PRLTAO0031-900710.1103/PhysRevLett.99.230602]. The average gyrating
dynamics is originated from the absence of detailed balance due to unequal
thermal baths. We look into the details of this stochastic gyrating dynamics, its
dependences on the temperature difference and coupling strength, and the
mechanism of heat transfer through this simple electronic circuit. Our work
affirms the general principle and the possibility of a Brownian ratchet working
near room temperature scale.
PMID- 29347041
TI - Collision rate coefficient for charged dust grains in the presence of linear
shear.
AB - Like and oppositely charged particles or dust grains in linear shear flows are
often driven to collide with one another by fluid and/or electrostatic forces,
which can strongly influence particle-size distribution evolution. In gaseous
media, collisions in shear are further complicated because particle inertia can
influence differential motion. Expressions for the collision rate coefficient
have not been developed previously which simultaneously account for the
influences of linear shear, particle inertia, and electrostatic interactions.
Here, we determine the collision rate coefficient accounting for the
aforementioned effects by determining the collision area, i.e., the area of the
plane perpendicular to the shear flow defining the relative initial locations of
particles which will collide with one another. Integration of the particle flux
over this area yields the collision rate. Collision rate calculations are
parametrized as an enhancement factor, i.e., the ratio of the collision rate
considering potential interactions and inertia to the traditional collision rate
considering laminar shear only. For particles of constant surface charge density,
the enhancement factor is found dependent only on the Stokes number (quantifying
particle inertia), the electrostatic energy to shear energy ratio, and the ratio
of colliding particle radii. Enhancement factors are determined for Stokes
numbers in the 0-10 range and energy ratios up to 5. Calculations show that the
influences of both electrostatic interactions and inertia are significant; for
inertialess (St=0) equal-sized and oppositely charged particles, we find that
even at energy ratios as low as 0.2, enhancement factors are in excess of 2. For
the same situation but like-charged particles, enhancement factors fall below
0.5. Increasing the Stokes number acts to mitigate the influence of electrostatic
potentials for both like and oppositely charged particles; i.e., inertia reduces
the enhancement factor for oppositely charged particles and increases it for like
charged particles. Uniquely, at elevated Stokes numbers with attractive
potentials we find collisionless "pockets" within the collision area, which are
regions completely bounded by the collision area but within which collisions do
not occur. Regression equations to results are provided, enabling calculation of
the enhancement factor as a function of energy ratio and Stokes number. In total,
this study both leads to insight into the collision dynamics of finite-inertia,
charged particles in shear flows, and provides a means to simply calculate the
particle-particle collision rate coefficient.
PMID- 29347042
TI - Probing the excited-state quantum phase transition through statistics of
Loschmidt echo and quantum work.
AB - By analyzing the probability distributions of the Loschmidt echo (LE) and quantum
work, we examine the nonequilibrium effects of a quantum many-body system, which
exhibits an excited-state quantum phase transition (ESQPT). We find that
depending on the value of the controlling parameter the distribution of the LE
displays different patterns. At the critical point of the ESQPT, both the
averaged LE and the averaged work show a cusplike shape. Furthermore, by
employing the finite-size scaling analysis of the averaged work, we obtain the
critical exponent of the ESQPT. Finally, we show that at the critical point of
ESQPT the eigenstate is a highly localized state, further highlighting the
influence of the ESQPT on the properties of the many-body system.
PMID- 29347043
TI - Scaling laws for the mechanics of loose and cohesive granular materials based on
Baxter's sticky hard spheres.
AB - We have conducted discrete element simulations (pfc3d) of very loose, cohesive,
granular assemblies with initial configurations which are drawn from Baxter's
sticky hard sphere (SHS) ensemble. The SHS model is employed as a promising
auxiliary means to independently control the coordination number z_{c} of
cohesive contacts and particle volume fraction phi of the initial states. We
focus on discerning the role of z_{c} and phi for the elastic modulus, failure
strength, and the plastic consolidation line under quasistatic, uniaxial
compression. We find scaling behavior of the modulus and the strength, which both
scale with the cohesive contact density nu_{c}=z_{c}phi of the initial state
according to a power law. In contrast, the behavior of the plastic consolidation
curve is shown to be independent of the initial conditions. Our results show the
primary control of the initial contact density on the mechanics of cohesive
granular materials for small deformations, which can be conveniently, but not
exclusively explored within the SHS-based assembling procedure.
PMID- 29347044
TI - Monte Carlo simulations of the XY vectorial Blume-Emery-Griffiths model in
multilayer films for ^{3}He-^{4}He mixtures.
AB - The XY vectorial generalization of the Blume-Emery-Griffiths (XY-VBEG) model,
which is suitable to be applied to the study of ^{3}He-^{4}He mixtures, is
treated on thin films structure and its thermodynamical properties are analyzed
as a function of the film thickness. We employ extensive and up-to-date Monte
Carlo simulations consisting of hybrid algorithms combining lattice-gas moves,
Metropolis, Wolff, and super-relaxation procedures to overcome the critical
slowing down and correlations among different spin configurations of the system.
We also make use of single histogram techniques to get the behavior of the
thermodynamical quantities close to the corresponding transition temperatures.
Thin films of the XY-VBEG model present a quite rich phase diagram with
Berezinskii-Kosterlitz-Thouless (BKT) transitions, BKT endpoints, and isolated
critical points. As one varies the impurity concentrations along the layers, and
in the limit of infinite film thickness, there is a coalescence of the BKT
transition endpoint and the isolated critical point into a single, unique
tricritical point. In addition, when mimicking the behavior of thin films of
^{3}He-^{4}He mixtures, one obtains that the concentration of ^{3}He atoms
decreases from the outer layers to the inner layers of the film, meaning that the
superfluid particles tend to locate in the bulk of the system.
PMID- 29347045
TI - Effect of disorder on shrinkage-induced fragmentation of a thin brittle layer.
AB - We investigate the effect of the amount of disorder on the shrinkage-induced
cracking of a thin brittle layer attached to a substrate. Based on a discrete
element model we study how the dynamics of cracking and the size of fragments
evolve when the amount of disorder is varied. In the model a thin layer is
discretized on a random lattice of Voronoi polygons attached to a substrate. Two
sources of disorder are considered: structural disorder captured by the local
variation of the stiffness and strength disorder represented by the random
strength of cohesive elements between polygons. Increasing the amount of strength
disorder, our calculations reveal a transition from a cellular crack pattern,
generated by the sequential branching and merging of cracks, to a disordered
ensemble of cracks where the merging of randomly nucleated microcracks dominate.
In the limit of low disorder, the statistics of fragment size is described by a
log-normal distribution; however, in the limit of high disorder, a power-law
distribution is obtained.
PMID- 29347047
TI - Interface tension in the improved Blume-Capel model.
AB - We study interfaces with periodic boundary conditions in the low-temperature
phase of the improved Blume-Capel model on the simple cubic lattice. The
interface free energy is defined by the difference of the free energy of a system
with antiperiodic boundary conditions in one of the directions and that of a
system with periodic boundary conditions in all directions. It is obtained by
integration of differences of the corresponding internal energies over the
inverse temperature. These differences can be computed efficiently by using a
variance reduced estimator that is based on the exchange cluster algorithm. The
interface tension is obtained from the interface free energy by using predictions
based on effective interface models. By using our numerical results for the
interface tension sigma and the correlation length xi obtained in previous work,
we determine the universal amplitude ratios
R_{2nd,+}=sigma_{0}f_{2nd,+}^{2}=0.3863(6), R_{2nd,-}=sigma_{0}f_{2nd,
}^{2}=0.1028(1), and R_{exp,-}=sigma_{0}f_{exp,-}^{2}=0.1077(3). Our results are
consistent with those obtained previously for the three-dimensional Ising model,
confirming the universality hypothesis.
PMID- 29347046
TI - Cortical geometry as a determinant of brain activity eigenmodes: Neural field
analysis.
AB - Perturbation analysis of neural field theory is used to derive eigenmodes of
neural activity on a cortical hemisphere, which have previously been calculated
numerically and found to be close analogs of spherical harmonics, despite heavy
cortical folding. The present perturbation method treats cortical folding as a
first-order perturbation from a spherical geometry. The first nine spatial
eigenmodes on a population-averaged cortical hemisphere are derived and compared
with previous numerical solutions. These eigenmodes contribute most to brain
activity patterns such as those seen in electroencephalography and functional
magnetic resonance imaging. The eigenvalues of these eigenmodes are found to
agree with the previous numerical solutions to within their uncertainties. Also
in agreement with the previous numerics, all eigenmodes are found to closely
resemble spherical harmonics. The first seven eigenmodes exhibit a one-to-one
correspondence with their numerical counterparts, with overlaps that are close to
unity. The next two eigenmodes overlap the corresponding pair of numerical
eigenmodes, having been rotated within the subspace spanned by that pair, likely
due to second-order effects. The spatial orientations of the eigenmodes are found
to be fixed by gross cortical shape rather than finer-scale cortical properties,
which is consistent with the observed intersubject consistency of functional
connectivity patterns. However, the eigenvalues depend more sensitively on finer
scale cortical structure, implying that the eigenfrequencies and consequent
dynamical properties of functional connectivity depend more strongly on details
of individual cortical folding. Overall, these results imply that well
established tools from perturbation theory and spherical harmonic analysis can be
used to calculate the main properties and dynamics of low-order brain eigenmodes.
PMID- 29347048
TI - Distribution of randomly diffusing particles in inhomogeneous media.
AB - Diffusion can be conceptualized, at microscopic scales, as the random hopping of
particles between neighboring lattice sites. In the case of diffusion in
inhomogeneous media, distinct spatial domains in the system may yield distinct
particle hopping rates. Starting from the master equations (MEs) governing
diffusion in inhomogeneous media we derive here, for arbitrary spatial
dimensions, the deterministic lattice equations (DLEs) specifying the average
particle number at each lattice site for randomly diffusing particles in
inhomogeneous media. We consider the case of free (Fickian) diffusion with no
steric constraints on the maximum particle number per lattice site as well as the
case of diffusion under steric constraints imposing a maximum particle
concentration. We find, for both transient and asymptotic regimes, excellent
agreement between the DLEs and kinetic Monte Carlo simulations of the MEs. The
DLEs provide a computationally efficient method for predicting the (average)
distribution of randomly diffusing particles in inhomogeneous media, with the
number of DLEs associated with a given system being independent of the number of
particles in the system. From the DLEs we obtain general analytic expressions for
the steady-state particle distributions for free diffusion and, in special cases,
diffusion under steric constraints in inhomogeneous media. We find that, in the
steady state of the system, the average fraction of particles in a given domain
is independent of most system properties, such as the arrangement and shape of
domains, and only depends on the number of lattice sites in each domain, the
particle hopping rates, the number of distinct particle species in the system,
and the total number of particles of each particle species in the system. Our
results provide general insights into the role of spatially inhomogeneous
particle hopping rates in setting the particle distributions in inhomogeneous
media.
PMID- 29347049
TI - Deviation from fluctuation-dissipation relation for driven superdiffusion:
Polymer stretching as an example.
AB - We discuss a deviation of the fluctuation-dissipation relation (FDR) in a driven
superdiffusive system as exemplified by polymer stretching. The superdiffusion is
found by monitoring momentum transfer to a tracer, which is a conjugate
observable with the position. Molecular-dynamics simulation demonstrates that the
FDR deviates during the nonequilibrium transient process. We then propose
nonequilibrium mode analysis for superdiffusion, which is a counterpart to that
for driven subdiffusion. The mode analysis yields results that are in qualitative
agreement with the simulation results, suggesting that the fluctuations of the
stiffness in the system from initial equilibrium to stretching account for the
FDR deviation.
PMID- 29347050
TI - Manipulation of double-stranded DNA melting by force.
AB - By integrating elasticity-as described by the Gaussian network model-with bond
binding energies that distinguish between different base-pair identities and
stacking configurations, we study the force induced melting of a double-stranded
DNA (dsDNA). Our approach is a generalization of our previous study of thermal
dsDNA denaturation [J. Chem. Phys. 145, 144101 (2016)JCPSA60021
960610.1063/1.4964285] to that induced by force at finite temperatures. It allows
us to obtain semimicroscopic information about the opening of the chain, such as
whether the dsDNA opens from one of the ends or from the interior, forming an
internal bubble. We study different types of force manipulation: (i) "end
unzipping," with force acting at a single end base pair perpendicular to the
helix, (ii) "midunzipping," with force acting at a middle base pair perpendicular
to the helix, and (iii) "end shearing," where the force acts at opposite ends
along the helix. By monitoring the free-energy landscape and probability
distribution of intermediate denaturation states, we show that different dominant
intermediate states are stabilized depending on the type of force manipulation
used. In particular, the bubble state of the sequence L60B36, which we have
previously found to be a stable state during thermal denaturation, is absent for
end unzipping and end shearing, whereas very similar bubbles are stabilized by
midunzipping, or when the force location is near the middle of the chain. Ours
results offer a simple tool for stabilizing bubbles and loops using force
manipulations at different temperatures, and may implicate on the mechanism in
which DNA enzymes or motors open regions of the chain.
PMID- 29347051
TI - Enhanced capital-asset pricing model for the reconstruction of bipartite
financial networks.
AB - Reconstructing patterns of interconnections from partial information is one of
the most important issues in the statistical physics of complex networks. A
paramount example is provided by financial networks. In fact, the spreading and
amplification of financial distress in capital markets are strongly affected by
the interconnections among financial institutions. Yet, while the aggregate
balance sheets of institutions are publicly disclosed, information on single
positions is mostly confidential and, as such, unavailable. Standard approaches
to reconstruct the network of financial interconnection produce unrealistically
dense topologies, leading to a biased estimation of systemic risk. Moreover,
reconstruction techniques are generally designed for monopartite networks of
bilateral exposures between financial institutions, thus failing in reproducing
bipartite networks of security holdings (e.g., investment portfolios). Here we
propose a reconstruction method based on constrained entropy maximization,
tailored for bipartite financial networks. Such a procedure enhances the
traditional capital-asset pricing model (CAPM) and allows us to reproduce the
correct topology of the network. We test this enhanced CAPM (ECAPM) method on a
dataset, collected by the European Central Bank, of detailed security holdings of
European institutional sectors over a period of six years (2009-2015). Our
approach outperforms the traditional CAPM and the recently proposed maximum
entropy CAPM both in reproducing the network topology and in estimating systemic
risk due to fire sales spillovers. In general, ECAPM can be applied to the whole
class of weighted bipartite networks described by the fitness model.
PMID- 29347052
TI - Capacitively coupled rf discharge with a large amount of microparticles:
Spatiotemporal emission pattern and microparticle arrangement.
AB - The effect of micron-sized particles on a low-pressure capacitively coupled rf
discharge is studied both experimentally and using numerical simulations. In the
laboratory experiments, microparticle clouds occupying a considerable fraction of
the discharge volume are supported against gravity with the help of the
thermophoretic force. The spatiotemporally resolved optical emission measurements
are performed with different arrangements of microparticles. The numerical
simulations are carried out on the basis of a one-dimensional hybrid (fluid
kinetic) discharge model describing the interaction between plasma and
microparticles in a self-consistent way. The study is focused on the role of
microparticle arrangement in interpreting the spatiotemporal emission
measurements. We show that it is not possible to reproduce simultaneously the
observed microparticle arrangement and emission pattern in the framework of the
considered one-dimensional model. This disagreement can be attributed to the two
dimensional effects (e.g., radial diffusion of the plasma components) or to the
lack of the proper description of the sharp void boundary in the frame of fluid
approach.
PMID- 29347053
TI - Radiation-pressure-driven ion Weibel instability and collisionless shocks.
AB - The Weibel instability from counterstreaming plasma flows is a basic process
highly relevant for collisionless shock formation in astrophysics. In this paper
we investigate, via two- and three-dimensional simulations, suitable
configurations for laboratory investigations of the ion Weibel instability (IWI)
driven by a fast quasineutral plasma flow launched into the target via the
radiation pressure of an ultra-high-intensity laser pulse ("hole-boring"
process). The use of S-polarized light at oblique incidence is found to be an
optimal configuration for driving IWI, as it prevents the development of surface
rippling observed at normal incidence that would lead to strong electron heating
and would favor competing instabilities. Conditions for the evolution of IWI into
a collisionless shock are also investigated.
PMID- 29347054
TI - Chaos-based wireless communication resisting multipath effects.
AB - In additive white Gaussian noise channel, chaos has been shown to be the optimal
coherent communication waveform in the sense of using a very simple matched
filter to maximize the signal-to-noise ratio. Recently, Lyapunov exponent
spectrum of the chaotic signals after being transmitted through a wireless
channel has been shown to be unaltered, paving the way for wireless communication
using chaos. In wireless communication systems, inter-symbol interference caused
by multipath propagation is one of the main obstacles to achieve high bit
transmission rate and low bit-error rate (BER). How to resist the multipath
effect is a fundamental problem in a chaos-based wireless communication system
(CWCS). In this paper, a CWCS is built to transmit chaotic signals generated by a
hybrid dynamical system and then to filter the received signals by using the
corresponding matched filter to decrease the noise effect and to detect the
binary information. We find that the multipath effect can be effectively resisted
by regrouping the return map of the received signal and by setting the
corresponding threshold based on the available information. We show that the
optimal threshold is a function of the channel parameters and of the information
symbols. Practically, the channel parameters are time-variant, and the future
information symbols are unavailable. In this case, a suboptimal threshold is
proposed, and the BER using the suboptimal threshold is derived analytically.
Simulation results show that the CWCS achieves a remarkable competitive
performance even under inaccurate channel parameters.
PMID- 29347055
TI - Renormalization group theory outperforms other approaches in statistical
comparison between upscaling techniques for porous media.
AB - Determining the pressure differential required to achieve a desired flow rate in
a porous medium requires solving Darcy's law, a Laplace-like equation, with a
spatially varying tensor permeability. In various scenarios, the permeability
coefficient is sampled at high spatial resolution, which makes solving Darcy's
equation numerically prohibitively expensive. As a consequence, much effort has
gone into creating upscaled or low-resolution effective models of the coefficient
while ensuring that the estimated flow rate is well reproduced, bringing to the
fore the classic tradeoff between computational cost and numerical accuracy. Here
we perform a statistical study to characterize the relative success of upscaling
methods on a large sample of permeability coefficients that are above the
percolation threshold. We introduce a technique based on mode-elimination
renormalization group theory (MG) to build coarse-scale permeability
coefficients. Comparing the results with coefficients upscaled using other
methods, we find that MG is consistently more accurate, particularly due to its
ability to address the tensorial nature of the coefficients. MG places a low
computational demand, in the manner in which we have implemented it, and accurate
flow-rate estimates are obtained when using MG-upscaled permeabilities that
approach or are beyond the percolation threshold.
PMID- 29347056
TI - Force-linearization closure for non-Markovian Langevin systems with time delay.
AB - This paper is concerned with the Fokker-Planck (FP) description of classical
stochastic systems with discrete time delay. The non-Markovian character of the
corresponding Langevin dynamics naturally leads to a coupled infinite hierarchy
of FP equations for the various n-time joint distribution functions. Here, we
present an approach to close the hierarchy at the one-time level based on a
linearization of the deterministic forces in all members of the hierarchy
starting from the second one. This leads to a closed equation for the one-time
probability density in the steady state. Considering two generic nonlinear
systems, a colloidal particle in a sinusoidal or bistable potential supplemented
by a linear delay force, we demonstrate that our approach yields a very accurate
representation of the density as compared to quasiexact numerical results from
direct solution of the Langevin equation. Moreover, the results are significantly
improved against those from a small-delay approximation and a perturbation
theoretical approach. We also discuss the possibility of accessing transport
related quantities, such as escape times, based on an additional Kramers
approximation. Our approach applies to a wide class of models with nonlinear
deterministic forces.
PMID- 29347057
TI - Revisiting the use of the immersed-boundary lattice-Boltzmann method for
simulations of suspended particles.
AB - The immersed-boundary lattice-Boltzmann method (IB-LBM) is increasingly being
used in simulations of dense suspensions. These systems are computationally very
expensive and can strongly benefit from lower resolutions that still maintain the
desired accuracy for the quantities of interest. IB-LBM has a number of free
parameters that have to be defined, often without exact knowledge of the
tradeoffs, since their behavior in low resolutions is not well understood. Such
parameters are the lattice constant Deltax, the number of vertices N_{v}, the
interpolation kernel phi, and the LBM relaxation time tau. We investigate the
effect of these IB-LBM parameters on a number of straightforward but challenging
benchmarks. The systems considered are (a) the flow of a single sphere in shear
flow, (b) the collision of two spheres in shear flow, and (c) the lubrication
interaction of two spheres. All benchmarks are performed in three dimensions. The
first two systems are used for determining two effective radii: the hydrodynamic
radius r_{hyd} and the particle interaction radius r_{inter}. The last system is
used to establish the numerical robustness of the lubrication forces, used to
probe the hydrodynamic interactions in the limit of small gaps. Our results show
that lower spatial resolutions result in larger hydrodynamic and interaction
radii, while surface densities should be chosen above two vertices per LU^{2}
result to prevent fluid penetration in underresolved meshes. Underresolved meshes
also failed to produce the migration of particles toward the center of the domain
due to lift forces in Couette flow, mostly noticeable for IBM-kernel phi_{2}.
Kernel phi_{4}, despite being more robust toward mesh resolution, produces a
notable membrane thickness, leading to the breakdown of the lubrication forces in
larger gaps, and its use in dense suspensions where the mean particle distances
are small can result in undesired behavior. r_{hyd} is measured to be different
from r_{inter}, suggesting that there is no consistent measure to recalibrate the
radius of the suspended particle.
PMID- 29347058
TI - Fluctuations in percolation of sparse complex networks.
AB - We study the role of fluctuations in percolation of sparse complex networks. To
this end we consider two random correlated realizations of the initial damage of
the nodes and we evaluate the fraction of nodes that are expected to remain in
the giant component of the network in both cases or just in one case. Our
framework includes a message-passing algorithm able to predict the fluctuations
in a single network, and an analytic prediction of the expected fluctuations in
ensembles of sparse networks. This approach is applied to real ecological and
infrastructure networks and it is shown to characterize the expected fluctuations
in their response to external damage.
PMID- 29347059
TI - Acoustic streaming in a microfluidic channel with a reflector: Case of a standing
wave generated by two counterpropagating leaky surface waves.
AB - A theory is developed for the modeling of acoustic streaming in a microfluidic
channel confined between an elastic solid wall and a rigid reflector. A situation
is studied where the acoustic streaming is produced by two leaky surface waves
that propagate towards each other in the solid wall and thus form a combined
standing wave in the fluid. Full analytical solutions are found for both the
linear acoustic field and the field of the acoustic streaming. A dispersion
equation is derived that allows one to calculate the wave speed in the system
under study. The obtained solutions are used to consider particular numerical
examples and to reveal the structure of the acoustic streaming. It is shown that
two systems of vortices are established along the boundaries of the microfluidic
channel.
PMID- 29347060
TI - Contact angle entropy and macroscopic friction in noncohesive two-dimensional
granular packings.
AB - We study the relationship between the granular contact angle distribution and
local particle friction on the macroscopic friction and bulk modulus in
noncohesive disk packings. Molecular dynamics in two dimensions are used to
simulate uniaxial loading-unloading cycles imposed on the granular packings.
While macroscopic Mohr friction depends on the granular pack geometric details,
it reaches a stationary limit after a finite number of loading-unloading cycles
that render well-defined values for bulk modulus, grain coordination, porosity,
and friction. For random packings and for all polydispersities analyzed, we found
that as interparticle friction increases, the bulk modulus for the limit cycle
decreases linearly, while the mean coordination number is reduced and the
porosity increased, also as approximately linear functions. On the other hand,
the macroscopic Mohr friction increases in a monotonous trend with interparticle
friction. The latter result is compared to a theoretical model that assumes the
existence of sliding planes corresponding to definite Mohr-friction values. The
simulation results for macroscopic friction are well described by the theoretical
model that incorporates the local neighbor angle distribution that can be
quantified through the contact angle entropy. As local friction is increased, the
limit entropy of the neighbor angle distribution is reduced, thus introducing the
geometric component to granular friction. Surprisingly, once the limit cycle is
reached, the Mohr friction seems to be insensitive to polydispersity as has been
recently reported.
PMID- 29347061
TI - Predictions of first passage times in sparse discrete fracture networks using
graph-based reductions.
AB - We present a graph-based methodology to reduce the computational cost of
obtaining first passage times through sparse fracture networks. We derive graph
representations of generic three-dimensional discrete fracture networks (DFNs)
using the DFN topology and flow boundary conditions. Subgraphs corresponding to
the union of the k shortest paths between the inflow and outflow boundaries are
identified and transport on their equivalent subnetworks is compared to transport
through the full network. The number of paths included in the subgraphs is based
on the scaling behavior of the number of edges in the graph with the number of
shortest paths. First passage times through the subnetworks are in good agreement
with those obtained in the full network, both for individual realizations and in
distribution. Accurate estimates of first passage times are obtained with an
order of magnitude reduction of CPU time and mesh size using the proposed method.
PMID- 29347062
TI - From thermal to excited-state quantum phase transition: The Dicke model.
AB - We study the thermodynamics of the full version of the Dicke model, including all
the possible values of the total angular momentum j, with both microcanonical and
canonical ensembles. We focus on both the excited-state quantum phase transition,
appearing in the microcanonical description of the maximum angular momentum
sector, j=N/2, and the thermal phase transition, which occurs when all the
sectors are taken into account. We show that two different features characterize
the full version of the Dicke model. If the system is in contact with a thermal
bath and is described by means of the canonical ensemble, the parity symmetry
becomes spontaneously broken at the critical temperature. In the microcanonical
ensemble, and despite that all the logarithmic singularities which characterize
the excited-state quantum phase transition are ruled out when all the j sectors
are considered, there still exists a critical energy (or temperature) dividing
the spectrum into two regions: one in which the parity symmetry can be broken,
and another in which this symmetry is always well defined.
PMID- 29347063
TI - Smallest quantum thermal machine: The effect of strong coupling and distributed
thermal tasks.
AB - The functions of the smallest self-contained thermal machine consisting of a
single qutrit are studied when the weak internal coupling assumption is relaxed.
It is shown that in the presence of one target to be cooled the strong coupling
is not beneficial to the refrigeration. The reason is explained by examining the
effect of the strong coupling on the contributions of all eigenstates transitions
to the heat current of the related thermal reservoir. When acting simultaneously
on two targets, the machine can be manipulated to implement distributed tasks on
them, such as cooling one target and meanwhile heating another one, by adjusting
the coupling strengths between the machine with the two targets. In particular,
we show that the machine can realize temperature reversal for the two qubits,
namely, the qubit that is coupled to the high temperature reservoir is
refrigerated to a temperature below that of the qubit contacting with the low
temperature reservoir.
PMID- 29347064
TI - Anisotropic decay of the energy spectrum in two-dimensional dense granular flows.
AB - We study anisotropic collective motions of two-dimensional granular particles
under simple shear deformations. Employing molecular-dynamics simulations of
large system sizes, we find that anisotropic fluidized bands develop in the
system yielding under quasistatic deformations, where the spectrum of nonaffine
velocities, which is associated with the energy spectrum for turbulent flows,
exhibits a quadrupole structure. To explain theoretically the anisotropic
spectrum, we derive hydrodynamic modes from a continuum model of dense granular
materials, where we find that fluidized bands are caused by long-lived
hydrodynamic fluctuations characterized by compressibility.
PMID- 29347065
TI - Theory of wavelet-based coarse-graining hierarchies for molecular dynamics.
AB - We present a multiresolution approach to compressing the degrees of freedom and
potentials associated with molecular dynamics, such as the bond potentials. The
approach suggests a systematic way to accelerate large-scale molecular
simulations with more than two levels of coarse graining, particularly
applications of polymeric materials. In particular, we derive explicit models for
(arbitrarily large) linear (homo)polymers and iterative methods to compute large
scale wavelet decompositions from fragment solutions. This approach does not
require explicit preparation of atomistic-to-coarse-grained mappings, but instead
uses the theory of diffusion wavelets for graph Laplacians to develop system
specific mappings. Our methodology leads to a hierarchy of system-specific coarse
grained degrees of freedom that provides a conceptually clear and mathematically
rigorous framework for modeling chemical systems at relevant model scales. The
approach is capable of automatically generating as many coarse-grained model
scales as necessary, that is, to go beyond the two scales in conventional coarse
grained strategies; furthermore, the wavelet-based coarse-grained models
explicitly link time and length scales. Furthermore, a straightforward method for
the reintroduction of omitted degrees of freedom is presented, which plays a
major role in maintaining model fidelity in long-time simulations and in
capturing emergent behaviors.
PMID- 29347066
TI - Mean-field approach to evolving spatial networks, with an application to
osteocyte network formation.
AB - We consider evolving networks in which each node can have various associated
properties (a state) in addition to those that arise from network structure. For
example, each node can have a spatial location and a velocity, or it can have
some more abstract internal property that describes something like a social
trait. Edges between nodes are created and destroyed, and new nodes enter the
system. We introduce a "local state degree distribution" (LSDD) as the degree
distribution at a particular point in state space. We then make a mean-field
assumption and thereby derive an integro-partial differential equation that is
satisfied by the LSDD. We perform numerical experiments and find good agreement
between solutions of the integro-differential equation and the LSDD from
stochastic simulations of the full model. To illustrate our theory, we apply it
to a simple model for osteocyte network formation within bones, with a view to
understanding changes that may take place during cancer. Our results suggest that
increased rates of differentiation lead to higher densities of osteocytes, but
with a smaller number of dendrites. To help provide biological context, we also
include an introduction to osteocytes, the formation of osteocyte networks, and
the role of osteocytes in bone metastasis.
PMID- 29347067
TI - Isotropic-nematic transition for hard rods on a three-dimensional cubic lattice.
AB - Using grand-canonical Monte Carlo (GCMC) simulations, we investigate the
isotropic-nematic phase transition for hard rods of size L*1*1 on a three
dimensional cubic lattice. We observe such a transition for L>=6. For L=6, the
nematic state has a negative order parameter, reflecting the co-occurrence of two
dominating orientations. For L>=7, the nematic state has a positive order
parameter, corresponding to the dominance of one orientation. We investigate rod
lengths up to L=25 and find evidence for a very weakly first-order isotropic
nematic transition, while we cannot completely rule out a second-order
transition. It was not possible to detect a density jump at the transition,
despite using large systems containing several 10^{5} particles. The probability
density distributions P(Q) from the GCMC simulations near the transition are very
broad, pointing to strong fluctuations. Our results complement earlier results on
the demixing (pseudonematic) transition for an equivalent system in two
dimensions, which is presumably of Ising type and occurs for L>=7. We compare our
results to lattice fundamental measure theory (FMT) and find that FMT strongly
overestimates nematic order and consequently predicts a strong first-order
transition. The rod packing fraction of the nematic coexisting states, however,
agree reasonably well between FMT and GCMC.
PMID- 29347068
TI - How to determine a boundary condition for diffusion at a thin membrane from
experimental data.
AB - We present a method of deriving a boundary condition for diffusion at a thin
membrane from experimental data. Based on experimental results obtained for
normal diffusion of ethanol in water, we show that the derived boundary condition
at a membrane contains a term with a Riemann-Liouville fractional time derivative
of order 1/2. Such a form of the boundary condition shows that a transfer of
particles through a thin membrane is a "long-memory process." The presented
method is an example that an important part of the mathematical model of physical
processes may be derived directly from experimental data.
PMID- 29347069
TI - Adaptive numerical algorithms to simulate the dynamical Casimir effect in a
closed cavity with different boundary conditions.
AB - We present an alternative numerical approach to compute the number of particles
created inside a cavity due to time-dependent boundary conditions. The physical
model consists of a rectangular cavity, where a wall always remains still while
the other wall of the cavity presents a smooth movement in one direction. The
method relies on the setting of the boundary conditions (Dirichlet and Neumann)
and the following resolution of the corresponding equations of modes. By a
further comparison between the ground state before and after the movement of the
cavity wall, we finally compute the number of particles created. To demonstrate
the method, we investigate the creation of particle production in vibrating
cavities, confirming previously known results in the appropriate limits. Within
this approach, the dynamical Casimir effect can be investigated, making it
possible to study a variety of scenarios where no analytical results are known.
Of special interest is, of course, the realistic case of the electromagnetic
field in a three-dimensional cavity, with transverse electric (TE)-mode and
transverse magnetic (TM)-mode photon production. Furthermore, with our approach
we are able to calculate numerically the particle creation in a tuneable resonant
superconducting cavity by the use of the generalized Robin boundary condition. We
compare the numerical results with analytical predictions as well as a different
numerical approach. Its extension to three dimensions is also straightforward.
PMID- 29347070
TI - Instabilities of conducting fluid layers in weak time-dependent magnetic fields.
AB - We present the experimental analysis of the instabilities generated on a large
drop of liquid metal by a time-dependent magnetic field. The study is done
exploring the range of tiny values of the control parameter (the ratio between
the Lorentz forces and inertia) avoiding nonlinear effects. Two different
instabilities break the symmetries generating spatial patterns that appear
without a threshold for some specific frequencies (up to the experimental
precision) and have been observed for parameter values two orders of magnitude
lower than in previously published experiments [J. Fluid Mech. 239, 383
(1992)JFLSA70022-112010.1017/S0022112092004452]. One of the instabilities
corresponds to a boundary condition oscillation that generates surface waves and
breaks the azimuthal symmetry. The other corresponds to a parametric forcing
through a modulation of the Lorentz force. The competition between these two
mechanisms produces time-dependent patterns near codimension-2 points.
PMID- 29347071
TI - Consistency of detrended fluctuation analysis.
AB - The scaling function F(s) in detrended fluctuation analysis (DFA) scales as
F(s)~s^{H} for stochastic processes with Hurst exponent H. This scaling law is
proven for stationary stochastic processes with 010^{17}cm^{-3} is measured for >100 ns. This is the
first temporal measurement of the generation and adiabatic expansion of a large
volume (3*10^{-4}cm^{3}) of warm dense plasma isochorically heated by intense
monochromatic electrons. The suite of diagnostics is presented, which includes
time-resolved plasma plume expansion measurements on a single shot, visible
spectroscopy measurements of the emission and absorption spectrum, measurements
of the beam distribution, and plans for the future.
PMID- 29347079
TI - Optimal information transfer in enzymatic networks: A field theoretic
formulation.
AB - Signaling in enzymatic networks is typically triggered by environmental
fluctuations, resulting in a series of stochastic chemical reactions, leading to
corruption of the signal by noise. For example, information flow is initiated by
binding of extracellular ligands to receptors, which is transmitted through a
cascade involving kinase-phosphatase stochastic chemical reactions. For a class
of such networks, we develop a general field-theoretic approach to calculate the
error in signal transmission as a function of an appropriate control variable.
Application of the theory to a simple push-pull network, a module in the kinase
phosphatase cascade, recovers the exact results for error in signal transmission
previously obtained using umbral calculus [Hinczewski and Thirumalai, Phys. Rev.
X 4, 041017 (2014)2160-330810.1103/PhysRevX.4.041017]. We illustrate the
generality of the theory by studying the minimal errors in noise reduction in a
reaction cascade with two connected push-pull modules. Such a cascade behaves as
an effective three-species network with a pseudointermediate. In this case,
optimal information transfer, resulting in the smallest square of the error
between the input and output, occurs with a time delay, which is given by the
inverse of the decay rate of the pseudointermediate. Surprisingly, in these
examples the minimum error computed using simulations that take nonlinearities
and discrete nature of molecules into account coincides with the predictions of a
linear theory. In contrast, there are substantial deviations between simulations
and predictions of the linear theory in error in signal propagation in an
enzymatic push-pull network for a certain range of parameters. Inclusion of
second-order perturbative corrections shows that differences between simulations
and theoretical predictions are minimized. Our study establishes that a field
theoretic formulation of stochastic biological signaling offers a systematic way
to understand error propagation in networks of arbitrary complexity.
PMID- 29347080
TI - Derivation of stable Burnett equations for rarefied gas flows.
AB - A set of constitutive relations for the stress tensor and heat flux vector for
the hydrodynamic description of rarefied gas flows is derived in this work. A
phase density function consistent with Onsager's reciprocity principle and H
theorem is utilized to capture nonequilibrium thermodynamics effects. The phase
density function satisfies the linearized Boltzmann equation and the collision
invariance property. Our formulation provides the correct value of the Prandtl
number as it involves two different relaxation times for momentum and energy
transport by diffusion. Generalized three-dimensional constitutive equations for
different kinds of molecules are derived using the phase density function. The
derived constitutive equations involve cross single derivatives of field
variables such as temperature and velocity, with no higher-order derivative in
higher-order terms. This is remarkable feature of the equations as the number of
boundary conditions required is the same as needed for conventional Navier-Stokes
equations. Linear stability analysis of the equations is performed, which shows
that the derived equations are unconditionally stable. A comparison of the
derived equations with existing Burnett-type equations is presented and salient
features of our equations are outlined. The classic internal flow problem, force
driven compressible plane Poiseuille flow, is chosen to verify the stable Burnett
equations and the results for equilibrium variables are presented.
PMID- 29347081
TI - Phenomenological modeling of durotaxis.
AB - Cells exhibit qualitatively different behaviors on substrates with different
rigidities. The fact that cells are more polarized on the stiffer substrate
motivates us to construct a two-dimensional cell with the distribution of focal
adhesions dependent on substrate rigidities. This distribution affects the forces
exerted by the cell and thereby determines its motion. Our model reproduces the
experimental observation that the persistence time is higher on the stiffer
substrate. This stiffness-dependent persistence will lead to durotaxis, the
preference in moving towards stiffer substrates. This propensity is characterized
by the durotaxis index first defined in experiments. We derive and validate a two
dimensional corresponding Fokker-Planck equation associated with our model. Our
approach highlights the possible role of the focal adhesion arrangement in
durotaxis.
PMID- 29347082
TI - Definite existence of subphases with eight- and ten-layer unit cells as studied
by complementary methods, electric-field-induced birefringence and microbeam
resonant x-ray scattering.
AB - A mixture of two selenium-containing compounds, 80 wt. % AS657 and 20 wt. %
AS620, are studied with two complementary methods, electric-field-induced
birefringence (EFIB) and microbeam resonant x-ray scattering (MURXS). The mixture
shows the typical phase sequence of Sm-C_{A}^{*}-1/3-1/2-Sm-C^{*}-Sm
C_{alpha}^{*}-Sm-A, where 1/3 and 1/2 are two prototypal ferrielectric and
antiferroelectric subphases with three- and four-layer unit cells, respectively.
Here we designate the subphase as its q_{T} number defined by the ratio of
[F]/([F]+[A]), where [F] and [A] are the numbers of synclinic ferroelectric and
anticlinic antiferroelectric orderings in the unit cell, respectively. The
electric field vs temperature phase diagram with EFIB contours indicates the
emergence of three additional subphases, an antiferroelectric one between Sm
C_{A}^{*} and 1/3 and antiferroelectric and apparently ferrielectric ones between
1/3 and 1/2. The simplest probable q_{T}'s for these additional subphases are
1/4, 2/5, and 3/7, respectively, in the order of increasing temperature. The
MURXS profiles indicate that antiferroelectric 1/4 and 2/5 approximately have the
eight-layer (FAAAFAAA) and ten-layer (FAFAAFAFAA) Ising unit cells, respectively.
The remaining subphase may be ferrielectric 3/7 with a seven-layer unit cell,
although the evidence is partial. These experimental results are compared with
the phenomenological Landau model [P. V. Dolganov and E. I. Kats, Liq. Cryst.
Rev. 1, 127 (2014)2168-039610.1080/21680396.2013.869667] and the quasimolecular
model [A. V. Emelyanenko and M. A. Osipov, Phys. Rev. E 68, 051703 (2003)1063
651X10.1103/PhysRevE.68.051703].
PMID- 29347083
TI - Contact of a spherical probe with a stretched rubber substrate.
AB - We report on a theoretical and experimental investigation of the normal contact
of stretched neo-Hookean substrates with rigid spherical probes. Starting from a
published formulation of surface Green's function for incremental displacements
on a prestretched, neo-Hookean, substrate [J. Mech. Phys. Solids 56, 2957
(2008)JMPSA80022-509610.1016/j.jmps.2008.07.002], a model is derived for both
adhesive and nonadhesive contacts. The shape of the elliptical contact area
together with the contact load and the contact stiffness are predicted as a
function of the in-plane stretch ratios lambda_{x} and lambda_{y} of the
substrate. The validity of this model is assessed by contact experiments carried
out using an uniaxally stretched silicone rubber. For stretch ratio below about
1.25, a good agreement is observed between theory and experiments. Above this
threshold, some deviations from the theoretical predictions are induced as a
result of the departure of the mechanical response of the silicone rubber from
the neo-Hokeean description embedded in the model.
PMID- 29347084
TI - Identifying the linear phase of the relativistic Kelvin-Helmholtz instability and
measuring its growth rate via radiation.
AB - For the relativistic Kelvin-Helmholtz instability (KHI), which occurs at shear
interfaces between two plasma streams, we report results on the polarized
radiation over all observation directions and frequencies emitted by the plasma
electrons from ab initio kinetic simulations. We find the polarization of the
radiation to provide a clear signature for distinguishing the linear phase of the
KHI from its other phases. During the linear phase, we predict the growth rate of
the KHI radiation power to match the growth rate of the KHI to a high degree. Our
predictions are based on a model of the vortex dynamics, which describes the
electron motion in the vicinity of the shear interface between the two streams.
Albeit the complex and turbulent dynamics happening in the shear region, we find
excellent agreement between our model and large-scale particle-in-cell
simulations. Our findings pave the way for identifying the KHI linear regime and
for measuring its growth rate in astrophysical jets observable on earth as well
as in laboratory plasmas.
PMID- 29347085
TI - Optimizing mutual synchronization of rhythmic spatiotemporal patterns in reaction
diffusion systems.
AB - Optimization of the stability of synchronized states between a pair of
symmetrically coupled reaction-diffusion systems exhibiting rhythmic
spatiotemporal patterns is studied in the framework of the phase reduction
theory. The optimal linear filter that maximizes the linear stability of the in
phase synchronized state is derived for the case in which the two systems are
nonlocally coupled. The optimal nonlinear interaction function that theoretically
gives the largest linear stability of the in-phase synchronized state is also
derived. The theory is illustrated by using typical rhythmic patterns in FitzHugh
Nagumo systems as examples.
PMID- 29347086
TI - Aggregation-fragmentation-diffusion model for trail dynamics.
AB - We investigate statistical properties of trails formed by a random process
incorporating aggregation, fragmentation, and diffusion. In this stochastic
process, which takes place in one spatial dimension, two neighboring trails may
combine to form a larger one, and also one trail may split into two. In addition,
trails move diffusively. The model is defined by two parameters which quantify
the fragmentation rate and the fragment size. In the long-time limit, the system
reaches a steady state, and our focus is the limiting distribution of trail
weights. We find that the density of trail weight has power-law tail P(w)~w^{
gamma} for small weight w. We obtain the exponent gamma analytically and find
that it varies continuously with the two model parameters. The exponent gamma can
be positive or negative, so that in one range of parameters small-weight trails
are abundant and in the complementary range they are rare.
PMID- 29347087
TI - Parallel random target searches in a confined space.
AB - We study a random target searching performed by N independent searchers in a d
dimensional domain of a large but finite volume. Considering the two initial
distributions of searchers where searchers are either uniformly or point
distributed, we estimate the mean time for the first of the searchers to reach
the target and refer to it as searching time. The searching time for the
uniformly distributed searchers exhibits a universal power-law dependence on N,
irrespective of dimensionality and the target-to-domain size ratio. For point
distributed searching, the searching time has a logarithmic dependence on N in
the large N limit, while in the small N limit, it shows qualitatively different
behaviors depending upon r_{0}, the initial distance of the searchers from a
target. We obtain a diagram by comparing the searching times of the two initial
distributions in the parameter space (r_{0},N) and therein present the asymptotic
lines separating three characteristic regions to explain numerical simulation
results.
PMID- 29347088
TI - Effect of polymer additives on heat transport and large-scale circulation in
turbulent Rayleigh-Benard convection.
AB - The present paper presents direct numerical simulations of Rayleigh-Benard
convection (RBC) in an enclosed cell filled with the polymer solution in order to
investigate the viscoelastic effect on the characteristics of heat transport and
large-scale circulation (LSC) of RBC. To overcome the difficulties in numerically
solving a high Weissenberg number (Wi) problem of viscoelastic fluid flow with
strong elastic effect, the log-conformation reformulation method was implemented.
Numerical results showed that the addition of polymers reduced the heat flux and
the amount of heat transfer reduction (HTR) behaves nonmonotonically, which
firstly increases but then decreases with Wi. The maximum HTR reaches around 8.7%
at the critical Wi. The nonmonotonic behavior of HTR as a function of Wi was then
corroborated with the modifications of the period of LSC and turbulent energy as
well as viscous boundary layer thickness. Finally, a standard turbulent kinetic
energy (TKE) budget analysis was done for the whole domain, the boundary layer
region, and the bulk region. It showed that the role change of elastic stress
contributions to TKE is mainly responsible for this nonmonotonic behavior of HTR.
PMID- 29347089
TI - Alternative steady states in ecological networks.
AB - In many natural situations, one observes a local system with many competing
species that is coupled by weak immigration to a regional species pool. The
dynamics of such a system is dominated by its stable and uninvadable (SU) states.
When the competition matrix is random, the number of SUs depends on the average
value and variance of its entries. Here we consider the problem in the limit of
weak competition and large variance. Using a yes-no interaction model, we show
that the number of SUs corresponds to the number of maximum cliques in an Erdos
Renyi network. The number of SUs grows exponentially with the number of species
in this limit, unless the network is completely asymmetric. In the asymmetric
limit, the number of SUs is O(1). Numerical simulations suggest that these
results are valid for models with a continuous distribution of competition terms.
PMID- 29347090
TI - Phase-field lattice Boltzmann modeling of boiling using a sharp-interface energy
solver.
AB - The main objective of this paper is to extend an isothermal incompressible two
phase lattice Boltzmann equation method to model liquid-vapor phase change
problems using a sharp-interface energy solver. Two discrete particle
distribution functions, one for the continuity equation and the other for the
pressure evolution and momentum equations, are considered in the current model.
The sharp-interface macroscopic internal energy equation is discretized with an
isotropic finite difference method to find temperature distribution in the
system. The mass flow generated at liquid-vapor phase interface is embedded in
the pressure evolution equation. The sharp-interface treatment of internal energy
equation helps to find the interfacial mass flow rate accurately where no free
parameter is needed in the calculations. The proposed model is verified against
available theoretical solutions of the two-phase Stefan problem and the two-phase
sucking interface problem, with which our simulation results are in good
agreement. The liquid droplet evaporation in a superheated vapor, the vapor
bubble growth in a superheated liquid, and the vapor bubble rising in a
superheated liquid are analyzed and underlying physical characteristics are
discussed in detail. The model is successfully tested for the liquid-vapor phase
change with large density ratio up to 1000.
PMID- 29347091
TI - Graph spectral characterization of the XY model on complex networks.
AB - There is recent evidence that the XY spin model on complex networks can display
three different macroscopic states in response to the topology of the network
underpinning the interactions of the spins. In this work we present a way to
characterize the macroscopic states of the XY spin model based on the spectral
decomposition of time series using topological information about the underlying
networks. We use three different classes of networks to generate time series of
the spins for the three possible macroscopic states. We then use the temporal
Graph Signal Transform technique to decompose the time series of the spins on the
eigenbasis of the Laplacian. From this decomposition, we produce spatial power
spectra, which summarize the activation of structural modes by the nonlinear
dynamics, and thus coherent patterns of activity of the spins. These signatures
of the macroscopic states are independent of the underlying network class and can
thus be used as robust signatures for the macroscopic states. This work opens
avenues to analyze and characterize dynamics on complex networks using temporal
Graph Signal Analysis.
PMID- 29347092
TI - Front roughening of flames in discrete media.
AB - The morphology of flame fronts propagating in reactive systems composed of
randomly positioned, pointlike sources is studied. The solution of the
temperature field and the initiation of new sources is implemented using the
superposition of the Green's function for the diffusion equation, eliminating the
need to use finite-difference approximations. The heat released from triggered
sources diffuses outward from each source, activating new sources and enabling a
mechanism of flame propagation. Systems of 40000 sources in a 200*200 two
dimensional domain were tracked using computer simulations, and statistical
ensembles of 120 realizations of each system were averaged to determine the
statistical properties of the flame fronts. The reactive system of sources is
parameterized by two nondimensional values: the heat release time (normalized by
interparticle diffusion time) and the ignition temperature (normalized by
adiabatic flame temperature). These two parameters were systematically varied for
different simulations to investigate their influence on front propagation. For
sufficiently fast heat release and low ignition temperature, the front roughness
[defined as the root mean square deviation of the ignition temperature contour
from the average flame position] grew following a power-law dependence that was
in excellent agreement with the Kardar-Parisi-Zhang (KPZ) universality class
(beta=1/3). As the reaction time was increased, lower values of the roughening
exponent were observed, and at a sufficiently great value of reaction time,
reversion to a steady, constant-width thermal flame was observed that matched the
solution from classical combustion theory. Deviation away from KPZ scaling was
also observed as the ignition temperature was increased. The features of this
system that permit it to exhibit both KPZ and non-KPZ scaling are discussed.
PMID- 29347093
TI - Self-assembly of rigid magnetic rods consisting of single dipolar beads in two
dimensions.
AB - Molecular dynamics simulations are used to investigate the structural properties
of a two-dimensional ensemble of magnetic rods, which are modeled as aligned
single dipolar beads. The obtained self-assembled configurations can be
characterized as (1) clusters, (2) percolated, and (3) ordered structures, and
their structural properties are investigated in detail. By increasing the aspect
ratio of the magnetic rods, we show that the percolation transition is suppressed
due to the reduced mobility of the rods in two dimensions. Such a behavior is
opposite to the one observed in three dimensions. A magnetic bulk phase is found
with local ferromagnetic order and an unusual nonmonotonic behavior of the
nematic order is observed.
PMID- 29347094
TI - Perturbation scheme for a fluxon in a curved Josephson junction.
AB - The kink solution in the long Josephson junction is studied. The perturbation
scheme of constructing the fluxon solution in curved junction is formulated. The
prediction from the perturbation scheme is compared with the prediction that
follows from the numerical studies of the complete field model.
PMID- 29347095
TI - Viscorotational shear instability of Keplerian granular flows.
AB - The linear stability of viscous Keplerian flow around a gravitating center is
studied using the rheological granular fluid model. The linear rheological
instability triggered by the interplay of the shear rheology and Keplerian
differential rotation of incompressible dense granular fluids is found.
Instability sets in in granular fluids, where the viscosity parameter grows
faster than the square of the local shear rate (strain rate) at constant
pressure. Found instability can play a crucial role in the dynamics of dense
planetary rings and granular flows in protoplanetary disks.
PMID- 29347096
TI - Random blebbing motion: A simple model linking cell structural properties to
migration characteristics.
AB - If the plasma membrane of a cell is able to delaminate locally from its actin
cortex, a cellular bleb can be produced. Blebs are pressure-driven protrusions,
which are noteworthy for their ability to produce cellular motion. Starting from
a general continuum mechanics description, we restrict ourselves to considering
cell and bleb shapes that maintain approximately spherical forms. From this
assumption, we obtain a tractable algebraic system for bleb formation. By
including cell-substrate adhesions, we can model blebbing cell motility. Further,
by considering mechanically isolated blebbing events, which are randomly
distributed over the cell, we can derive equations linking the macroscopic
migration characteristics to the microscopic structural parameters of the cell.
This multiscale modeling framework is then used to provide parameter estimates,
which are in agreement with current experimental data. In summary, the
construction of the mathematical model provides testable relationships between
the bleb size and cell motility.
PMID- 29347097
TI - Extreme and superextreme events in a loss-modulated CO_{2} laser: Nonlinear
resonance route and precursors.
AB - We investigate the occurrence of extreme and rare events, i.e., giant and rare
light pulses, in a periodically modulated CO_{2} laser model. Due to nonlinear
resonant processes, we show a scenario of interaction between chaotic bands of
different orders, which may lead to the formation of extreme and rare events. We
identify a crisis line in the modulation parameter space, and we show that, when
the modulation amplitude increases, remaining in the vicinity of the crisis, some
statistical properties of the laser pulses, such as the average and dispersion of
amplitudes, do not change much, whereas the amplitude of extreme events grows
enormously, giving rise to extreme events with much larger deviations than
usually reported, with a significant probability of occurrence, i.e., with a long
tailed non-Gaussian distribution. We identify recurrent regular patterns, i.e.,
precursors, that anticipate the emergence of extreme and rare events, and we
associate these regular patterns with unstable periodic orbits embedded in a
chaotic attractor. We show that the precursors may or may not lead to the
emergence of extreme events. Thus, we compute the probability of success or
failure (false alarm) in the prediction of the extreme events, once a precursor
is identified in the deterministic time series. We show that this probability
depends on the accuracy with which the precursor is identified in the laser
intensity time series.
PMID- 29347098
TI - Statistics of randomly cross-linked polymer models to interpret chromatin
conformation capture data.
AB - Polymer models are used to describe chromatin, which can be folded at different
spatial scales by binding molecules. By folding, chromatin generates loops of
various sizes. We present here a statistical analysis of the randomly cross
linked (RCL) polymer model, where monomer pairs are connected randomly,
generating a heterogeneous ensemble of chromatin conformations. We obtain
asymptotic formulas for the steady-state variance, encounter probability, the
radius of gyration, instantaneous displacement, and the mean first encounter time
between any two monomers. The analytical results are confirmed by Brownian
simulations. Finally, the present results are used to extract the mean number of
cross links in a chromatin region from conformation capture data.
PMID- 29347099
TI - Heat engines at optimal power: Low-dissipation versus endoreversible model.
AB - The low-dissipation model and the endoreversible model of heat engines are two of
the most commonly studied models of machines in finite-time thermodynamics. In
this paper we compare the performance characteristics of these two models under
optimal power output. We point out a basic equivalence between them, in the
linear response regime.
PMID- 29347100
TI - Correcting binding parameters for interacting ligand-lattice systems.
AB - Binding of ligands to macromolecules is central to many functional and regulatory
biological processes. Key parameters characterizing ligand-macromolecule
interactions are the stoichiometry, inducing the number of ligands per
macromolecule binding site, and the dissociation constant, quantifying the ligand
binding site affinity. Both these parameters can be obtained from analyses of
classical saturation experiments using the standard binding equation that offers
the great advantage of mathematical simplicity but becomes an approximation for
situations of interest when a ligand binds and covers more than one single
binding site on the macromolecule. Using the framework of car-parking problem
with latticelike macromolecules where each ligand can cover simultaneously
several consecutive binding sites, we showed that employing the standard analysis
leads to underestimation of binding parameters, i.e., ligands appear larger than
they actually are and their affinity is also greater than it is. Therefore, we
have derived expressions allowing to determine the ligand size and true binding
parameters (stoichiometry and dissociation constant) as a function of apparent
binding parameters retrieved from standard saturation experiments.
PMID- 29347101
TI - Formation of liquid drops at an orifice and dynamics of pinch-off in liquid jets.
AB - This paper presents a numerical investigation of the dynamics of pinch-off in
liquid drops and jets during injection of a liquid through an orifice into
another fluid. The current study is carried out by solving axisymmetric Navier
Stokes equations and the interface is captured using a coupled level-set and
volume-of-fluid approach. The delicate interplay of inertia and viscous effects
plays a crucial role in deciding the dynamics of the formation as well as breakup
of liquid drops and jets. In the dripping regime, the growth and breakup rate of
a drop are studied and quantified by corroborating with theoretical predictions.
During the growth stage of the drops, a self-similar behavior of the drop profile
is identified over a relatively short duration of time. The viscosity of the drop
liquid shows substantial influence on the thinning behavior of a liquid neck and
a transition is observed from an inertia dominated regime to an inertia-viscous
regime beyond a critical minimum value of the neck radius. The phenomenon of
interface overturning is fundamentally related to the magnitude of drop
viscosity. The variation of overturning angle as a function of drop viscosity is
computed and a critical value of Ohnesorge number is obtained beyond which
overturning ceases. Increasing the inertia of drop liquid transforms the system
from a periodically dripping regime to a quasiperiodic regime and finally it
culminates into an elongated liquid jet. Another interesting transition from
dripping to jetting regime is demonstrated by varying the viscosity of the
ambient medium. The breakup of jets in Rayleigh mode is explored and the breakup
length obtained from our computations shows excellent agreement with the
theoretical predictions owing to Rayleigh's analysis. The ambient medium is
entrained as the jet moves downstream with the creation of a vortical structure
just outside the jet signifying increased participation of the ambient medium in
the dynamics of jet breakup at higher inflow rates.
PMID- 29347102
TI - Crack-tip process zone as a bifurcation problem.
AB - Stress concentration at a crack tip generates a solid structural transformation
in its vicinity, the process zone. We argue that its formation represents a local
phase transition described by a multicomponent order parameter. We derive a
system of equations describing the dynamics of the order parameter driven by an
inhomogeneous, time-dependent stress field in the solid and show that it exhibits
a bifurcation. The latter corresponds to the emergence of a process zone
characterized by the distribution of the order parameter localized in the
vicinity of the crack tip. The emergence temperature T_{*} considerably differs
from the temperature of the bulk phase transformation T_{c}. We demonstrate that
T_{*} exhibits a universal behavior T_{*}-T_{c}~K_{I}^{4/3}, in terms of the
stress intensity factor K_{I}, and that the zone universally vanishes upon
achieving a critical velocity. These facts together give rise to a universal
dynamic phase diagram.
PMID- 29347103
TI - Shortcuts to isothermality and nonequilibrium work relations.
AB - In conventional thermodynamics, it is widely acknowledged that the realization of
an isothermal process for a system requires a quasistatic controlling protocol.
Here we propose and design a strategy to realize a finite-rate isothermal
transition from an equilibrium state to another one at the same temperature,
which is named the "shortcut to isothermality." By using shortcuts to
isothermality, we derive three nonequilibrium work relations, including an
identity between the free-energy difference and the mean work due to the
potential of the original system, a Jarzynski-like equality, and the inverse
relationship between the dissipated work and the total driving time. We
numerically test these three relations by considering the motion of a Brownian
particle trapped in a harmonic potential and dragged by a time-dependent force.
PMID- 29347104
TI - Visibility graphs of random scalar fields and spatial data.
AB - We extend the family of visibility algorithms to map scalar fields of arbitrary
dimension into graphs, enabling the analysis of spatially extended data
structures as networks. We introduce several possible extensions and provide
analytical results on the topological properties of the graphs associated to
different types of real-valued matrices, which can be understood as the high and
low disorder limits of real-valued scalar fields. In particular, we find a closed
expression for the degree distribution of these graphs associated to uncorrelated
random fields of generic dimension. This result holds independently of the
field's marginal distribution and it directly yields a statistical randomness
test, applicable in any dimension. We showcase its usefulness by discriminating
spatial snapshots of two-dimensional white noise from snapshots of a two
dimensional lattice of diffusively coupled chaotic maps, a system that generates
high dimensional spatiotemporal chaos. The range of potential applications of
this combinatorial framework includes image processing in engineering, the
description of surface growth in material science, soft matter or medicine, and
the characterization of potential energy surfaces in chemistry, disordered
systems, and high energy physics. An illustration on the applicability of this
method for the classification of the different stages involved in carcinogenesis
is briefly discussed.
PMID- 29347105
TI - Lattice gas with molecular dynamics collision operator.
AB - We introduce a lattice gas implementation that is based on coarse-graining a
molecular dynamics (MD) simulation. Such a lattice gas is similar to standard
lattice gases, but its collision operator is informed by an underlying MD
simulation. This can be considered an optimal lattice gas implementation because
it allows for the representation of any system that can be simulated with MD. We
show here that equilibrium behavior of the popular lattice Boltzmann algorithm is
consistent with this optimal lattice gas. This comparison allows us to make a
more accurate identification of the expressions for temperature and pressure in
lattice Boltzmann simulations, which turn out to be related not only to the
physical temperature and pressure but also to the lattice discretization. We show
that for any spatial discretization, we need to choose a particular temporal
discretization to recover the lattice Boltzmann equilibrium.
PMID- 29347106
TI - Criticality in Brownian ensembles.
AB - A Brownian ensemble appears as a nonequilibrium state of transition from one
universality class of random matrix ensembles to another one. The parameter
governing the transition is, in general, size-dependent, resulting in a rapid
approach of the statistics, in infinite size limit, to one of the two
universality classes. Our detailed analysis, however, reveals the appearance of a
new scale-invariant spectral statistics, nonstationary along the spectrum,
associated with multifractal eigenstates, and different from the two end-points
if the transition parameter becomes size-independent. The number of such critical
points during transition is governed by a competition between the average
perturbation strength and the local spectral density. The results obtained here
have applications to wide-ranging complex systems, e.g., those modeled by
multiparametric Gaussian ensembles or column constrained ensembles.
PMID- 29347107
TI - Hawkes process model with a time-dependent background rate and its application to
high-frequency financial data.
AB - A Hawkes process model with a time-varying background rate is developed for
analyzing the high-frequency financial data. In our model, the logarithm of the
background rate is modeled by a linear model with a relatively large number of
variable-width basis functions, and the parameters are estimated by a Bayesian
method. Our model can capture not only the slow time variation, such as in the
intraday seasonality, but also the rapid one, which follows a macroeconomic news
announcement. By analyzing the tick data of the Nikkei 225 mini, we find that (i)
our model is better fitted to the data than the Hawkes models with a constant
background rate or a slowly varying background rate, which have been commonly
used in the field of quantitative finance; (ii) the improvement in the goodness
of-fit to the data by our model is significant especially for sessions where
considerable fluctuation of the background rate is present; and (iii) our model
is statistically consistent with the data. The branching ratio, which quantifies
the level of the endogeneity of markets, estimated by our model is 0.41,
suggesting the relative importance of exogenous factors in the market dynamics.
We also demonstrate that it is critically important to appropriately model the
time-dependent background rate for the branching ratio estimation.
PMID- 29347108
TI - In silico optimization of critical currents in superconductors.
AB - For many technological applications of superconductors the performance of a
material is determined by the highest current it can carry losslessly-the
critical current. In turn, the critical current can be controlled by adding
nonsuperconducting defects in the superconductor matrix. Here we report on
systematic comparison of different local and global optimization strategies to
predict optimal structures of pinning centers leading to the highest possible
critical currents. We demonstrate performance of these methods for a
superconductor with randomly placed spherical, elliptical, and columnar defects.
PMID- 29347109
TI - Traveling waves in a spring-block chain sliding down a slope.
AB - Traveling waves are studied in a spring slider-block model. We explicitly
construct front waves (kinks) for a piecewise-linear spinodal friction force.
Pulse waves are obtained as the matching of two traveling fronts with identical
speeds. Explicit formulas are obtained for the wavespeed and the wave form in the
anticontinuum limit. The link with localized waves in a Burridge-Knopoff model of
an earthquake fault is briefly discussed.
PMID- 29347110
TI - Influence of a dispersion of magnetic and nonmagnetic nanoparticles on the
magnetic Fredericksz transition of the liquid crystal 5CB.
AB - A long time ago, Brochard and de Gennes predicted the possibility of
significantly decreasing the critical magnetic field of the Fredericksz
transition (the magnetic Fredericksz threshold) in a mixture of nematic liquid
crystals and ferromagnetic particles, the so-called ferronematics. This
phenomenon is rarely measured to be large, due to soft homeotropic anchoring
induced at the nanoparticle surface. Here we present an optical study of the
magnetic Fredericksz transition combined with a light scattering study of the
classical nematic liquid crystal: the pentylcyanobiphenyl (5CB), doped with 6 nm
diameter magnetic and nonmagnetic nanoparticles. Surprisingly, for both
nanoparticles, we observe at room temperature a net decrease of the threshold
field of the Fredericksz transition at low nanoparticle concentrations, which
appears associated with a coating of the nanoparticles by a brush of
polydimethylsiloxane copolymer chains inducing planar anchoring of the director
on the nanoparticle surface. Moreover, the magnetic Fredericksz threshold
exhibits nonmonotonic behavior as a function of the nanoparticle concentration
for both types of nanoparticles, first decreasing down to a value from 23% to 31%
below that of pure 5CB, then increasing with a further increase of nanoparticle
concentration. This is interpreted as an aggregation starting at around 0.02
weight fraction that consumes more isolated nanoparticles than those introduced
when the concentration is increased above c=0.05 weight fraction (volume fraction
3.5*10^{-2}). This shows the larger effect of isolated nanoparticles on the
threshold with respect to aggregates. From dynamic light scattering measurements
we deduced that, if the decrease of the magnetic threshold when the nanoparticle
concentration increases is similar for both kinds of nanoparticles, the origin of
this decrease is different for magnetic and nonmagnetic nanoparticles. For
nonmagnetic nanoparticles, the behavior may be associated with a decrease of the
elastic constant due to weak planar anchoring. For magnetic nanoparticles there
are non-negligible local magnetic interactions between liquid crystal molecules
and magnetic nanoparticles, leading to an increase of the average order
parameter. This magnetic interaction thus favors an easier liquid crystal
director rotation in the presence of external magnetic field, able to reorient
the magnetic moments of the nanoparticles along with the molecules.
PMID- 29347111
TI - Eigenstate thermalization in the two-dimensional transverse field Ising model.
II. Off-diagonal matrix elements of observables.
AB - We study the matrix elements of few-body observables, focusing on the off
diagonal ones, in the eigenstates of the two-dimensional transverse field Ising
model. By resolving all symmetries, we relate the onset of quantum chaos to the
structure of the matrix elements. In particular, we show that a general result of
the theory of random matrices, namely, the value 2 of the ratio of variances
(diagonal to off-diagonal) of the matrix elements of Hermitian operators, occurs
in the quantum chaotic regime. Furthermore, we explore the behavior of the off
diagonal matrix elements of observables as a function of the eigenstate energy
differences and show that it is in accordance with the eigenstate thermalization
hypothesis ansatz.
PMID- 29347112
TI - Statistics, distillation, and ordering emergence in a two-dimensional stochastic
model of particles in counterflowing streams.
AB - In this paper, we propose a stochastic model which describes two species of
particles moving in counterflow. The model generalizes the theoretical framework
that describes the transport in random systems by taking into account two
different scenarios: particles can work as mobile obstacles, whereas particles of
one species move in the opposite direction to the particles of the other species,
or particles of a given species work as fixed obstacles remaining in their places
during the time evolution. We conduct a detailed study about the statistics
concerning the crossing time of particles, as well as the effects of the lateral
transitions on the time required to the system reaches a state of complete
geographic separation of species. The spatial effects of jamming are also studied
by looking into the deformation of the concentration of particles in the two
dimensional corridor. Finally, we observe in our study the formation of patterns
of lanes which reach the steady state regardless of the initial conditions used
for the evolution. A similar result is also observed in real experiments
involving charged colloids motion and simulations of pedestrian dynamics based on
Langevin equations, when periodic boundary conditions are considered (particles
counterflow in a ring symmetry). The results obtained through Monte Carlo
simulations and numerical integrations are in good agreement with each other.
However, differently from previous studies, the dynamics considered in this work
is not Newton-based, and therefore, even artificial situations of self-propelled
objects should be studied in this first-principles modeling.
PMID- 29347113
TI - Counting statistics of chaotic resonances at optical frequencies: Theory and
experiments.
AB - A deformed dielectric microcavity is used as an experimental platform for the
analysis of the statistics of chaotic resonances, in the perspective of testing
fractal Weyl laws at optical frequencies. In order to surmount the difficulties
that arise from reading strongly overlapping spectra, we exploit the mixed nature
of the phase space at hand, and only count the high-Q whispering-gallery modes
(WGMs) directly. That enables us to draw statistical information on the more
lossy chaotic resonances, coupled to the high-Q regular modes via dynamical
tunneling. Three different models [classical, Random-Matrix-Theory (RMT) based,
semiclassical] to interpret the experimental data are discussed. On the basis of
least-squares analysis, theoretical estimates of Ehrenfest time, and independent
measurements, we find that a semiclassically modified RMT-based expression best
describes the experiment in all its realizations, particularly when the resonator
is coupled to visible light, while RMT alone still works quite well in the
infrared. In this work we reexamine and substantially extend the results of a
short paper published earlier [L. Wang et al., Phys. Rev. E 93, 040201(R)
(2016)2470-004510.1103/PhysRevE.93.040201].
PMID- 29347114
TI - Passive scalar transport by a non-Gaussian turbulent flow in the Batchelor
regime.
AB - We analyze passive scalar advection by a turbulent flow in the Batchelor regime.
No restrictions on the velocity statistics of the flow are assumed. The
properties of the scalar are derived from the statistical properties of velocity;
analytic expressions for the moments of scalar density are obtained. We show that
the scalar statistics can differ significantly from that obtained in the frames
of the Kraichnan model.
PMID- 29347115
TI - Multiple-relaxation-time lattice Boltzmann simulation for flow, mass transfer,
and adsorption in porous media.
AB - In this paper, to predict the dynamics behaviors of flow and mass transfer with
adsorption phenomena in porous media at the representative elementary volume
(REV) scale, a multiple-relaxation-time (MRT) lattice Boltzmann (LB) model for
the convection-diffusion equation is developed to solve the transfer problem with
an unsteady source term in porous media. Utilizing the Chapman-Enskog analysis,
the modified MRT-LB model can recover the macroscopic governing equations at the
REV scale. The coupled MRT-LB model for momentum and mass transfer is validated
by comparing with the finite-difference method and the analytical solution.
Moreover, using the MRT-LB method coupled with the linear driving force model,
the fluid transfer and adsorption behaviors of the carbon dioxide in a porous
fixed bed are explored. The breakthrough curve of adsorption from MRT-LB
simulation is compared with the experimental data and the finite-element
solution, and the transient concentration distributions of the carbon dioxide
along the porous fixed bed are elaborated upon in detail. In addition, the MRT-LB
simulation results show that the appearance time of the breakthrough point in the
breakthrough curve is advanced as the mass transfer resistance in the linear
driving force model increases; however, the saturation point is prolonged
inversely.
PMID- 29347116
TI - Orientational dynamics of fluctuating dipolar particles assembled in a mesoscopic
colloidal ribbon.
AB - We combine experiments and theory to investigate the dynamics and orientational
fluctuations of ferromagnetic microellipsoids that form a ribbonlike structure
due to attractive dipolar forces. When assembled in the ribbon, the ellipsoids
display orientational thermal fluctuations with an amplitude that can be
controlled via application of an in-plane magnetic field. We use video microscopy
to investigate the orientational dynamics in real time and space. Theoretical
arguments are used to derive an analytical expression that describes how the
distribution of the different angular configurations depends on the strength of
the applied field. The experimental data are in good agreement with the developed
model for all the range of field parameters explored. Understanding the role of
fluctuations in chains composed of dipolar particles is important not only from a
fundamental point of view, but it may also help understanding the stability of
such structures against thermal noise, which is relevant in microfluidics and
laboratory-on-a-chip applications.
PMID- 29347117
TI - Molecular-dynamics study on characteristics of energy and tangential momentum
accommodation coefficients.
AB - Gas-surface interaction is studied by the molecular dynamics method to
investigate qualitatively characteristics of accommodation coefficients. A large
number of trajectories of gas molecules colliding to and scattering from a
surface are statistically analyzed to calculate the energy (thermal)
accommodation coefficient (EAC) and the tangential momentum accommodation
coefficient (TMAC). Considering experimental measurements of the accommodation
coefficients, the incident velocities are stochastically sampled to represent a
bulk condition. The accommodation coefficients for noble gases show qualitative
coincidence with experimental values. To investigate characteristics of these
accommodation coefficients in detail, the gas-surface interaction is
parametrically studied by varying the molecular mass of gas, the gas-surface
interaction strength, and the molecular size of gas, one by one. EAC increases
with increasing every parameter, while TMAC increases with increasing the
interaction strength, but decreases with increasing the molecular mass and the
molecular size. Thus, contradictory results in experimentally measured TMAC for
noble gases could result from the difference between the surface conditions
employed in the measurements in the balance among the effective parameters of
molecular mass, interaction strength, and molecular size, due to surface
roughness and/or adsorbed molecules. The accommodation coefficients for a thermo
fluid dynamics field with a temperature difference between gas and surface and a
bulk flow at the same time are also investigated.
PMID- 29347118
TI - Linear stability of layered two-phase flows through parallel soft-gel-coated
walls.
AB - The linear stability of layered two-phase Poiseuille flows through soft-gel
coated parallel walls is studied in this work. The focus is on determining the
effect of the elastohydrodynamic coupling between the fluids and the soft-gel
layers on the different instabilities observed in flows between parallel plates.
The fluids are assumed Newtonian and incompressible, while the soft gels are
modeled as linear viscoelastic solids. A long-wave asymptotic analysis is used to
obtain an analytical expression for the growth rate of the disturbances. A
Chebyshev collocation method is used to numerically solve the general linearized
equations. Three distinct instability modes are identified in the flow: (a) a
liquid-liquid long-wave mode; (b) a liquid-liquid short-wave mode; (c) a gel
liquid short-wave mode. The effect of deformability of the soft gels on these
three modes is analyzed. From the long-wave analysis of the liquid-liquid mode a
stability map is obtained, in which four different regions are clearly
demarcated. It is shown that introducing a gel layer near the more viscous fluid
has a predominantly stabilizing effect on this mode seen in flows between rigid
plates. For parameters where this mode is stable for flow between rigid plates,
introducing a gel layer near the less viscous and thinner fluid has a
predominantly destabilizing effect. The liquid-liquid short-wave mode is
destabilized by the introduction of soft-gel layers. Additional instability modes
at the gel-liquid interfaces induced by the deformability of the soft-gel layers
are identified. We show that these can be controlled by varying the thickness of
the gel layers. Insights into the physical mechanism driving different
instabilities are obtained using an energy budget analysis.
PMID- 29347119
TI - Disentangling structural information from core-level excitation spectra.
AB - Core-level spectra of liquids can be difficult to interpret due to the presence
of a range of local environments. We present computational methods for
investigating core-level spectra based on the idea that both local structural
parameters and the x-ray spectra behave as functions of the local atomic
configuration around the absorbing site. We identify correlations between
structural parameters and spectral intensities in defined regions of interest,
using the oxygen K-edge excitation spectrum of liquid water as a test case. Our
results show that this kind of analysis can find the main structure-spectral
relationships of ice, liquid water, and supercritical water.
PMID- 29347120
TI - Microscopic muon dynamics in the polymer electrolyte poly(ethylene oxide).
AB - The microscopic dynamics of protons (H^{+}) in poly(ethylene oxide) (PEO) have
been investigated through a study of implanted positive muons (Mu^{+}), which can
be considered a light proton analog. The exponential decay of the muon spin
polarization in zero magnetic field indicated that Mu^{+} hopping is in the fast
fluctuation limit between 140 and 310 K and the relaxation rate was found to be
sensitive to the glass transition. Mu^{+} dynamics in PEO was monitored via the
relaxation of the muon spin polarization in a transverse field of 10 mT.
Activated hopping of Mu^{+} was observed above the glass transition temperature
with an activation barrier of 122+/-1 meV. The temperature dependence of the
diamagnetic muon polarization in PEO can be explained by diffusion of radiolytic
electrons.
PMID- 29347121
TI - Recurrence in the high-order nonlinear Schrodinger equation: A low-dimensional
analysis.
AB - We study a three-wave truncation of the high-order nonlinear Schrodinger equation
for deep-water waves (also named Dysthe equation). We validate the model by
comparing it to numerical simulation; we distinguish the impact of the different
fourth-order terms and classify the solutions according to their topology. This
allows us to properly define the temporary spectral upshift occurring in the
nonlinear stage of Benjamin-Feir instability and provides a tool for studying
further generalizations of this model.
PMID- 29347122
TI - Impact of the kinetic boundary condition on porous media flow in the lattice
Boltzmann formulation.
AB - To emphasize the importance of the kinetic boundary condition for micro- to
nanoscale flow, we present an ad hoc kinetic boundary condition suitable for
torturous geological porous media. We found that the kinetic boundary condition
is one of the essential features which should be supplemented to the standard
lattice Boltzmann scheme in order to obtain accurate continuum observables. The
claim is validated using a channel flow setup by showing the agreement of mass
flux with analytical value. Further, using a homogeneous porous structure, the
importance of the kinetic boundary condition is shown by comparing the
permeability correction factor with the analytical value. Finally, the proposed
alternate to the kinetic boundary condition is validated by showing its
capability to capture the basic feature of the kinetic boundary condition.
PMID- 29347123
TI - Dislocation-free growth of quasicrystals from two seeds due to additional
phasonic degrees of freedom.
AB - We explore the growth of two-dimensional quasicrystals, i.e., aperiodic
structures that possess long-range order, from two seeds at various distances and
with different orientations by using dynamical phase-field crystal calculations.
We compare the results to the growth of periodic crystals from two seeds. There,
a domain border consisting of dislocations is observed in case of large distances
between the seed and large angles between their orientation. Furthermore, a
domain border is found if the seeds are placed at a distance that does not fit to
the periodic lattice. In the case of the growth of quasicrystals, we only observe
domain borders for large distances and different orientations. Note that all
distances do inherently not match to a perfect domain wall-free quasicrystalline
structure. Nevertheless, we find dislocation-free growth for all seeds at a small
enough distance and for all seeds that approximately have the same orientation.
In periodic structures, the stress that occurs due to incommensurate distances
between the seeds results in phononic strain fields or, in the case of too large
stresses, in dislocations. In contrast, in quasicrystals an additional phasonic
strain field can occur and suppress dislocations. Phasons are additional degrees
of freedom that are unique to quasicrystals. As a consequence, the additional
phasonic strain field helps to distribute the stress and facilitates the growth
of dislocation-free quasicrystals from multiple seeds. In contrast, in the
periodic case the growth from multiple seeds most likely leads to a structure
with multiple domains. Our work lays the theoretical foundations for growing
perfect quasicrystals from different seeds and is therefore relevant for many
applications.
PMID- 29347124
TI - Controllability of flow-conservation networks.
AB - The ultimate goal of exploring complex networks is to control them. As such,
controllability of complex networks has been intensively investigated. Despite
recent advances in studying the impact of a network's topology on its
controllability, a comprehensive understanding of the synergistic impact of
network topology and dynamics on controllability is still lacking. Here, we
explore the controllability of flow-conservation networks, trying to identify the
minimal number of driver nodes that can guide the network to any desirable state.
We develop a method to analyze the controllability on flow-conservation networks
based on exact controllability theory, transforming the original analysis on
adjacency matrix to Laplacian matrix. With this framework, we systematically
investigate the impact of some key factors of networks, including link density,
link directionality, and link polarity, on the controllability of these networks.
We also obtain the analytical equations by investigating the network's structural
properties approximatively and design the efficient tools. Finally, we consider
some real networks with flow dynamics, finding that their controllability is
significantly different from that predicted by only considering the topology.
These findings deepen our understanding of network controllability with flow
conservation dynamics and provide a general framework to incorporate real
dynamics in the analysis of network controllability.
PMID- 29347125
TI - Interplay of different environments in open quantum systems: Breakdown of the
additive approximation.
AB - We analyze an open quantum system under the influence of more than one
environment: a dephasing bath and a probability-absorbing bath that represents a
decay channel, as encountered in many models of quantum networks. In our case,
dephasing is modeled by random fluctuations of the site energies, while the
absorbing bath is modeled with an external lead attached to the system. We
analyze under which conditions the effects of the two baths can enter additively
the quantum master equation. When such additivity is legitimate, the reduced
master equation corresponds to the evolution generated by an effective non
Hermitian Hamiltonian and a Haken-Strobl dephasing super-operator. We find that
the additive decomposition is a good approximation when the strength of dephasing
is small compared to the bandwidth of the probability-absorbing bath.
PMID- 29347126
TI - Requisite ingredients for thermal rectification.
AB - The present work is devoted to an analytical investigation of the thermal
rectification mechanism. More specifically, we attempt to find the requisite
ingredients for such a phenomenon to occur. Starting from the linearization of
the time evolution equations of anharmonic chains of oscillators, we propose some
effective harmonic toy models with a potential that is dependent on temperature,
and we investigate their steady heat currents. This unusual temperature-dependent
potential is the footprint of nonlinearity in the final effective linear model.
The approach is not restricted to any particular regime of heat transport. Our
results show that thermal rectification holds in a system if it has asymmetric
parameters related to its own structure, e.g., a graded particle mass
distribution and some other parameters or features dependent on the inner
temperatures that change as we invert the baths at the boundaries. The
description of rectification in these simplified models, with minimal
ingredients, shows that it is a ubiquitous phenomenon, and it may serve as a
guide for further research.
PMID- 29347127
TI - Long-time instability in the Runge-Kutta algorithm for a Nose-Hoover heat bath of
a harmonic chain and its stabilization.
AB - In this paper, we investigate the Runge-Kutta algorithm for the Nose-Hoover heat
bath of a harmonic chain. The Runge-Kutta algorithm is found to be unstable in
long-time calculations, with the system temperature growing exponentially. The
growth rate increases if time step size is chosen larger. By analyzing the
Fourier spectra in both space (wave number) and time (frequency), we discover
that the growth is caused by spurious energy accumulation, particularly at the
largest wave number. Such accumulation may be explained by von Neumann analysis
for an infinite chain, with the nonlinear heat bath being ignored. Furthermore,
we propose to add a filter to remove excessive energy, which effectively
stabilizes the algorithm.
PMID- 29347128
TI - Finite-size effect on optimal efficiency of heat engines.
AB - The optimal efficiency of quantum (or classical) heat engines whose heat baths
are n-particle systems is given by the strong large deviation. We give the
optimal work extraction process as a concrete energy-preserving unitary time
evolution among the heat baths and the work storage. We show that our optimal
work extraction turns the disordered energy of the heat baths to the ordered
energy of the work storage, by evaluating the ratio of the entropy difference to
the energy difference in the heat baths and the work storage, respectively. By
comparing the statistical mechanical optimal efficiency with the macroscopic
thermodynamic bound, we evaluate the accuracy of the macroscopic thermodynamics
with finite-size heat baths from the statistical mechanical viewpoint. We also
evaluate the quantum coherence effect on the optimal efficiency of the cycle
processes without restricting their cycle time by comparing the classical and
quantum optimal efficiencies.
PMID- 29347129
TI - Boundary-layer effects in droplet splashing.
AB - A drop falling onto a solid substrate will disintegrate into smaller parts when
its impact velocity V exceeds the so-called critical velocity for splashing,
i.e., when V>V^{*}. Under these circumstances, the very thin liquid sheet, which
is ejected tangentially to the solid after the drop touches the substrate, lifts
off as a consequence of the aerodynamic forces exerted on it. Subsequently, the
growth of capillary instabilities breaks the toroidal rim bordering the ejecta
into smaller droplets, violently ejected radially outward, provoking the splash
[G. Riboux and J. M. Gordillo, Phys. Rev. Lett. 113, 024507 (2014)]PRLTAO0031
900710.1103/PhysRevLett.113.024507. In this contribution, the effect of the
growth of the boundary layer is included in the splash model presented in Phys.
Rev. Lett. 113, 024507 (2014)PRLTAO0031-900710.1103/PhysRevLett.113.024507,
obtaining very good agreement between the measured and the predicted values of
V^{*} for wide ranges of liquid and gas material properties, atmospheric
pressures, and substrate wettabilities. Our description also modifies the way at
when the liquid sheet is first ejected, which can now be determined in a much
more straightforward manner than that proposed in Phys. Rev. Lett. 113, 024507
(2014)PRLTAO0031-900710.1103/PhysRevLett.113.024507.
PMID- 29347130
TI - Low-algorithmic-complexity entropy-deceiving graphs.
AB - In estimating the complexity of objects, in particular, of graphs, it is common
practice to rely on graph- and information-theoretic measures. Here, using
integer sequences with properties such as Borel normality, we explain how these
measures are not independent of the way in which an object, such as a graph, can
be described or observed. From observations that can reconstruct the same graph
and are therefore essentially translations of the same description, we see that
when applying a computable measure such as the Shannon entropy, not only is it
necessary to preselect a feature of interest where there is one, and to make an
arbitrary selection where there is not, but also more general properties, such as
the causal likelihood of a graph as a measure (opposed to randomness), can be
largely misrepresented by computable measures such as the entropy and entropy
rate. We introduce recursive and nonrecursive (uncomputable) graphs and graph
constructions based on these integer sequences, whose different lossless
descriptions have disparate entropy values, thereby enabling the study and
exploration of a measure's range of applications and demonstrating the weaknesses
of computable measures of complexity.
PMID- 29347131
TI - Minimum energy paths for conformational changes of viral capsids.
AB - In this work we study conformational changes of viral capsids using techniques of
large deviations theory for stochastic differential equations. The viral capsid
is a model of a complex system in which many units-the proteins forming the
capsomers-interact by weak forces to form a structure with exceptional mechanical
resistance. The destabilization of such a structure is interesting both, per se,
since it is related either to infection or maturation processes and because it
yields insights into the stability of complex structures in which the
constitutive elements interact by weak attractive forces. We focus here on a
simplified model of a dodecahedral viral capsid and assume that the capsomers are
rigid plaquettes with one degree of freedom each. We compute the most probable
transition path from the closed capsid to the final configuration using minimum
energy paths and discuss the stability of intermediate states.
PMID- 29347132
TI - Finite-size scaling in the system of coupled oscillators with heterogeneity in
coupling strength.
AB - We consider a mean-field model of coupled phase oscillators with random
heterogeneity in the coupling strength. The system that we investigate here is a
minimal model that contains randomness in diverse values of the coupling
strength, and it is found to return to the original Kuramoto model [Y. Kuramoto,
Prog. Theor. Phys. Suppl. 79, 223 (1984)10.1143/PTPS.79.223] when the coupling
heterogeneity disappears. According to one recent paper [H. Hong, H. Chate, L.-H.
Tang, and H. Park, Phys. Rev. E 92, 022122 (2015)10.1103/PhysRevE.92.022122],
when the natural frequency of the oscillator in the system is "deterministically"
chosen, with no randomness in it, the system is found to exhibit the finite-size
scaling exponent nu[over -]=5/4. Also, the critical exponent for the dynamic
fluctuation of the order parameter is found to be given by gamma=1/4, which is
different from the critical exponents for the Kuramoto model with the natural
frequencies randomly chosen. Originally, the unusual finite-size scaling behavior
of the Kuramoto model was reported by Hong et al. [H. Hong, H. Chate, H. Park,
and L.-H. Tang, Phys. Rev. Lett. 99, 184101 (2007)10.1103/PhysRevLett.99.184101],
where the scaling behavior is found to be characterized by the unusual exponent
nu[over -]=5/2. On the other hand, if the randomness in the natural frequency is
removed, it is found that the finite-size scaling behavior is characterized by a
different exponent, nu[over -]=5/4 [H. Hong, H. Chate, L.-H. Tang, and H. Park,
Phys. Rev. E 92, 022122 (2015)10.1103/PhysRevE.92.022122]. Those findings brought
about our curiosity and led us to explore the effects of the randomness on the
finite-size scaling behavior. In this paper, we pay particular attention to
investigating the finite-size scaling and dynamic fluctuation when the randomness
in the coupling strength is considered.
PMID- 29347133
TI - One-dimensional long-range percolation: A numerical study.
AB - In this paper we study bond percolation on a one-dimensional chain with power-law
bond probability C/r^{d+sigma}, where r is the distance length between distinct
sites and d=1. We introduce and test an order-N Monte Carlo algorithm and we
determine as a function of sigma the critical value C_{c} at which percolation
occurs. The critical exponents in the range 00.
PMID- 29347134
TI - Dynamics of scroll waves in a cylinder jacket geometry.
AB - The dynamics of scroll waves in a narrow cylinder jacket-shaped reactor is
investigated experimentally by optical tomography. The fate of the scroll waves
of excitation in the Belousov-Zhabotinsky reaction depends on the thickness of
the cylinder jacket. While at sufficiently wide cylinder jackets vertically
oriented scroll waves remain stable, the probability that the filament of a
scroll hits a lateral wall increases as the cylinder jacket narrows. This may
lead to the rupture of the initial filament and pinning of the filament ends at
the lateral walls. Filaments that pin to opposite lateral walls shrink and
reorient to a horizontal orientation; such a reorientation corresponds to a
transition from an intramural to a transmural scroll wave. The kinetics of the
reorientation and shrinkage of the scrolls were studied. Furthermore, we find
that no new filaments were generated upon collision of excitation waves at the
side of the cylinder jacket opposite to the scroll wave. Thus, under the studied
conditions, we do not observe any new generation of filaments due to a phenomenon
like reentry.
PMID- 29347135
TI - Discrete-time dynamic network model for the spread of susceptible-infective
recovered diseases.
AB - We propose a discrete-time dynamic network model describing the spread of
susceptible-infective-recovered diseases in a population. We consider the case in
which the nodes in the network change their links due to social mixing dynamics
as well as in response to the disease. The model shows the behavior that, as we
increase social mixing, disease spread is inhibited in certain cases, while in
other cases it is enhanced. We also extend this dynamic network model to take
into account the case of hidden infection. Here we find that, as expected, the
disease spreads more readily if there is a time period after contracting the
disease during which an individual is infective but is not known to have the
disease.
PMID- 29347136
TI - Linking initial microstructure and local response during quasistatic granular
compaction.
AB - We performed experiments combining three-dimensional x-ray diffraction and x-ray
computed tomography to explore the relationship between microstructure and local
force and strain during quasistatic granular compaction. We found that initial
void space around a grain and contact coordination number before compaction can
be used to predict regions vulnerable to above-average local force and strain at
later stages of compaction. We also found correlations between void space around
a grain and coordination number, and between grain stress and maximum
interparticle force, at all stages of compaction. Finally, we observed grains
that fracture to have an above-average initial local void space and a below
average initial coordination number. Our findings provide (1) a detailed
description of microstructure evolution during quasistatic granular compaction,
(2) an approach for identifying regions vulnerable to large values of strain and
interparticle force, and (3) methods for identifying regions of a material with
large interparticle forces and coordination numbers from measurements of grain
stress and local porosity.
PMID- 29347137
TI - Hyperuniformity of initial conditions and critical decay of a diffusive epidemic
process belonging to the Manna class.
AB - For a fixed-energy Manna sandpile model belonging to a Manna class in one
dimension (d=1), we recently showed that the critical decay is different for
random and regular initial conditions (ICs). Compared with previous results of
natural IC for several models, we suggested for the Manna class that the critical
decay depends on the characteristics of the three ICs. But the dependence on the
random and regular ICs was shown only for a single model. In this work, we study
the critical decay for the random and regular ICs for another model of the Manna
class in d=1, a diffusive epidemic process. It is shown that the critical decay
exponent agrees with the previous result for each IC, which verifies that IC
dependence is a common feature of the Manna class. In addition, for the random
and regular ICs, we measure the variance sigma^{2}(r) of total particle density
in a region of size r by increasing r up to system size and investigate its
temporal evolution toward the value sigma_{q}^{2}(r) of the quasisteady state at
criticality. In d=1,sigma^{2}(r) scales as sigma^{2}(r)~r^{-psi} with psi=1 for
random distributions and 1
that a random walk needs to cover completely a two-dimensional torus of size L*L.
They confirm the mathematical prediction that ~(LlnL)^{2} for large
L, but the prefactor seems to deviate significantly from the supposedly exact
result 4/pi derived by Dembo et al. [Ann. Math. 160, 433 (2004)ANMAAH0003
486X10.4007/annals.2004.160.433], if the most straightforward extrapolation is
used. On the other hand, we find that this scaling does hold for the time
T_{N(t)=1}(L) at which the average number of yet unvisited sites is 1, as also
predicted previously. This might suggest (wrongly) that and
T_{N(t)=1}(L) scale differently, although the distribution of rescaled cover
times becomes sharp in the limit L->infinity. But our results can be reconciled
with those of Dembo et al. by a very slow and nonmonotonic convergence of
/(LlnL)^{2}, as had been indeed proven by Belius et al. [Probab.
Theory Relat. Fields 167, 461 (2017)10.1007/s00440-015-0689-6] for Brownian
walks, and was conjectured by them to hold also for lattice walks.
PMID- 29347168
TI - Quantifying the entropic cost of cellular growth control.
AB - Viewing the ways a living cell can organize its metabolism as the phase space of
a physical system, regulation can be seen as the ability to reduce the entropy of
that space by selecting specific cellular configurations that are, in some sense,
optimal. Here we quantify the amount of regulation required to control a cell's
growth rate by a maximum-entropy approach to the space of underlying metabolic
phenotypes, where a configuration corresponds to a metabolic flux pattern as
described by genome-scale models. We link the mean growth rate achieved by a
population of cells to the minimal amount of metabolic regulation needed to
achieve it through a phase diagram that highlights how growth suppression can be
as costly (in regulatory terms) as growth enhancement. Moreover, we provide an
interpretation of the inverse temperature beta controlling maximum-entropy
distributions based on the underlying growth dynamics. Specifically, we show that
the asymptotic value of beta for a cell population can be expected to depend on
(i) the carrying capacity of the environment, (ii) the initial size of the
colony, and (iii) the probability distribution from which the inoculum was
sampled. Results obtained for E. coli and human cells are found to be remarkably
consistent with empirical evidence.
PMID- 29347169
TI - Nonlinear mechanics of rigidifying curves.
AB - Thin shells are characterized by a high cost of stretching compared to bending.
As a result isometries of the midsurface of a shell play a crucial role in their
mechanics. In turn, curves on the midsurface with zero normal curvature play a
critical role in determining the number and behavior of isometries. In this
paper, we show how the presence of these curves results in a decrease in the
number of linear isometries. Paradoxically, shells are also known to continuously
fold more easily across these rigidifying curves than other curves on the
surface. We show how including nonlinearities in the strain can explain these
phenomena and demonstrate folding isometries with explicit solutions to the
nonlinear isometry equations. In addition to explicit solutions, exact geometric
arguments are given to validate and guide our analysis in a coordinate-free way.
PMID- 29347170
TI - Information propagation in a noisy gene cascade.
AB - We use information theory to study the information transmission through a simple
gene cascade where the product of an unregulated gene regulates the expression
activity of a cooperative genetic switch. While the input signal is provided by
the upstream gene with two states, we consider that the expression of downstream
gene is controlled by a cis-regulatory system with three binding sites for the
regulator product, which can bind cooperatively. By computing exactly the
associated probability distributions, we estimate information transmission
thought the mutual information measure. We found that the mutual information
associated with unimodal input signal is lower than the associated with bimodal
inputs. We also observe that mutual information presents a maximum in the
cooperativity intensity, and the position of this maximum depends on the kinetic
rates of the promoter. Furthermore, we found that the bursting dynamics of the
input signal can enhance the information transmission capacity.
PMID- 29347171
TI - Properties and relative measure for quantifying quantum synchronization.
AB - Although quantum synchronization phenomena and corresponding measures have been
widely discussed recently, it is still an open question how to characterize
directly the influence of nonlocal correlation, which is the key distinction for
identifying classical and quantum synchronizations. In this paper, we present
basic postulates for quantifying quantum synchronization based on the related
theory in Mari's work [Phys. Rev. Lett. 111, 103605 (2013)PRLTAO0031
900710.1103/PhysRevLett.111.103605], and we give a general formula of a quantum
synchronization measure with clear physical interpretations. By introducing
Pearson's parameter, we show that the obvious characteristics of our measure are
the relativity and monotonicity. As an example, the measure is applied to
describe synchronization among quantum optomechanical systems under a Markovian
bath. We also show the potential by quantifying generalized synchronization and
discrete variable synchronization with this measure.
PMID- 29347172
TI - Dynamic finite-size scaling at first-order transitions.
AB - We investigate the dynamic behavior of finite-size systems close to a first-order
transition (FOT). We develop a dynamic finite-size scaling (DFSS) theory for the
dynamic behavior in the coexistence region where different phases coexist. This
is characterized by an exponentially large time scale related to the tunneling
between the two phases. We show that, when considering time scales of the order
of the tunneling time, the dynamic behavior can be described by a two-state
coarse-grained dynamics. This allows us to obtain exact predictions for the
dynamical scaling functions. To test the general DFSS theory at FOTs, we consider
the two-dimensional Ising model in the low-temperature phase, where the external
magnetic field drives a FOT, and the 20-state Potts model, which undergoes a
thermal FOT. Numerical results for a purely relaxational dynamics fully confirm
the general theory.
PMID- 29347173
TI - Hybrid colored noise process with space-dependent switching rates.
AB - A fundamental issue in the theory of continuous stochastic process is the
interpretation of multiplicative white noise, which is often referred to as the
Ito-Stratonovich dilemma. From a physical perspective, this reflects the need to
introduce additional constraints in order to specify the nature of the noise,
whereas from a mathematical perspective it reflects an ambiguity in the
formulation of stochastic differential equations (SDEs). Recently, we have
identified a mechanism for obtaining an Ito SDE based on a form of temporal
disorder. Motivated by switching processes in molecular biology, we considered a
Brownian particle that randomly switches between two distinct conformational
states with different diffusivities. In each state, the particle undergoes normal
diffusion (additive noise) so there is no ambiguity in the interpretation of the
noise. However, if the switching rates depend on position, then in the fast
switching limit one obtains Brownian motion with a space-dependent diffusivity of
the Ito form. In this paper, we extend our theory to include colored additive
noise. We show that the nature of the effective multiplicative noise process
obtained by taking both the white-noise limit (kappa->0) and fast switching limit
(epsilon->0) depends on the order the two limits are taken. If the white-noise
limit is taken first, then we obtain Ito, and if the fast switching limit is
taken first, then we obtain Stratonovich. Moreover, the form of the effective
diffusion coefficient differs in the two cases. The latter result holds even in
the case of space-independent transition rates, where one obtains additive noise
processes with different diffusion coefficients. Finally, we show that yet
another form of multiplicative noise is obtained in the simultaneous limit
epsilon,kappa->0 with epsilon/kappa^{2} fixed.
PMID- 29347174
TI - Periodic jetting and monodisperse jet drops from oblique gas injection.
AB - When air is blown in a straw or tube near an air-liquid interface, typically one
of two behaviors is observed: a dimple in the liquid's surface, or a frenzy of
sputtering bubbles, waves, and spray. Here we report and characterize an
intermediate regime that can develop when a confined air jet enters the interface
at an angle. This regime is oscillatory with a distinct characteristic frequency
and can develop periodic angled jets that can break up into monodisperse
aerosols. The underlying mechanisms responsible for this highly periodic regime
are not well understood. Here we flow a continuous stream of gas through a tube
near a liquid surface, observing both optically and acoustically the deformation
of the liquid-air interface as various parameters are systematically adjusted. We
show that the Kelvin-Helmholtz instability is responsible for the inception of
waves within a cavity formed by the gas. Inertia, gravity, and capillary forces
both shape the cavity and govern the frequency and amplitude of these gas-induced
cavity waves. The flapping cavity focuses the waves into a series of periodic
jets that can break up into droplets following the Rayleigh-Plateau instability.
We present scaling arguments to rationalize the fundamental frequencies driving
this system, as well as the conditions that bound the periodic regime. These
frequencies and conditions compare well with our experimental results.
PMID- 29347175
TI - Publisher's Note: Asymmetric transmission of sound wave in cavitating liquids
[Phys. Rev. E 95, 033118 (2017)].
AB - This corrects the article DOI: 10.1103/PhysRevE.95.033118.
PMID- 29347176
TI - Optimal allocation of resources for suppressing epidemic spreading on networks.
AB - Efficient allocation of limited medical resources is crucial for controlling
epidemic spreading on networks. Based on the susceptible-infected-susceptible
model, we solve the optimization problem of how best to allocate the limited
resources so as to minimize prevalence, providing that the curing rate of each
node is positively correlated to its medical resource. By quenched mean-field
theory and heterogeneous mean-field (HMF) theory, we prove that an epidemic
outbreak will be suppressed to the greatest extent if the curing rate of each
node is directly proportional to its degree, under which the effective infection
rate lambda has a maximal threshold lambda_{c}^{opt}=1/, where is the
average degree of the underlying network. For a weak infection region
(lambda?lambda_{c}^{opt}), we combine perturbation theory with the Lagrange
multiplier method (LMM) to derive the analytical expression of optimal allocation
of the curing rates and the corresponding minimized prevalence. For a general
infection region (lambda>lambda_{c}^{opt}), the high-dimensional optimization
problem is converted into numerically solving low-dimensional nonlinear equations
by the HMF theory and LMM. Counterintuitively, in the strong infection region the
low-degree nodes should be allocated more medical resources than the high-degree
nodes to minimize prevalence. Finally, we use simulated annealing to validate the
theoretical results.
PMID- 29347177
TI - Theory of helicoids and skyrmions in confined cholesteric liquid crystals.
AB - Cholesteric liquid crystals experience geometric frustration when they are
confined between surfaces with anchoring conditions that are incompatible with
the cholesteric twist. Because of this frustration, they develop complex
topological defect structures, which may be helicoids or skyrmions. We develop a
theory for these structures, which extends previous theoretical research by
deriving exact solutions for helicoids with the assumption of constant azimuth,
calculating numerical solutions for helicoids and skyrmions with varying azimuth,
and interpreting the results in terms of competition between terms in the free
energy.
PMID- 29347178
TI - Stability of the fluid interface in a Hele-Shaw cell subjected to horizontal
vibrations.
AB - The stability of the horizontal interface of two immiscible viscous fluids in a
Hele-Shaw cell subject to gravity and horizontal vibrations is studied. The
problem is reduced to the generalized Hill equation, which is solved analytically
by the multiple scale method and numerically. The long-wave instability, the
resonance (parametric resonance) excitation of waves at finite frequencies of
vibrations (for the first three resonances), and the limit of high-frequency
vibrations are studied analytically under the assumption of small amplitudes of
vibrations and small viscosity. For finite amplitudes of vibrations, finite wave
numbers, and finite viscosity, the study is performed numerically. The influence
of the specific natural control parameters and physical parameters of the system
on its instability threshold is discussed. The results provide extension to other
results [J. Bouchgl, S. Aniss, and M. Souhar, Phys. Rev. E 88, 023027
(2013)10.1103/PhysRevE.88.023027], where the authors considered a similar problem
but took into account viscosity in the basic state and did not consider it in the
equations for perturbations.
PMID- 29347179
TI - Classical ergodicity and quantum eigenstate thermalization: Analysis in fully
connected Ising ferromagnets.
AB - We investigate the relation between the classical ergodicity and the quantum
eigenstate thermalization in the fully connected Ising ferromagnets. In the case
of spin-1/2, an expectation value of an observable in a single-energy eigenstate
coincides with the long-time average in the underlying classical dynamics, which
is a consequence of the Wentzel-Kramers-Brillouin approximation. In the case of
spin-1, the underlying classical dynamics is not necessarily ergodic. In that
case, it turns out that, in the thermodynamic limit, the statistics of the
expectation values of an observable in the energy eigenstates coincides with the
statistics of the long-time averages in the underlying classical dynamics
starting from random initial states sampled uniformly from the classical phase
space. This feature seems to be a general property in semiclassical systems, and
the result presented here is crucial in discussing equilibration, thermalization,
and dynamical transitions of such systems.
PMID- 29347180
TI - Lattice Boltzmann modeling and simulation of liquid jet breakup.
AB - A three-dimensional color-fluid lattice Boltzmann model for immiscible two-phase
flows is developed in the framework of a three-dimensional 27-velocity (D3Q27)
lattice. The collision operator comprises the D3Q27 versions of three
suboperators: a multiple-relaxation-time (MRT) collision operator, a generalized
Liu-Valocchi-Kang perturbation operator, and a Latva-Kokko-Rothman recoloring
operator. A D3Q27 version of an enhanced equilibrium distribution function is
also incorporated into this model to improve the Galilean invariance. Three types
of numerical tests, namely, a static droplet, an oscillating droplet, and the
Rayleigh-Taylor instability, show a good agreement with analytical solutions and
numerical simulations. Following these numerical tests, this model is applied to
liquid-jet-breakup simulations. The simulation conditions are matched to the
conditions of the previous experiments. In this case, numerical stability is
maintained throughout the simulation, although the kinematic viscosity for the
continuous phase is set as low as 1.8*10^{-4}, in which case the corresponding
Reynolds number is 3.4*10^{3}; the developed lattice Boltzmann model based on the
D3Q27 lattice enables us to perform the simulation with parameters directly
matched to the experiments. The jet's liquid column transitions from an
asymmetrical to an axisymmetrical shape, and entrainment occurs from the side of
the jet. The measured time history of the jet's leading-edge position shows a
good agreement with the experiments. Finally, the reproducibility of the regime
map for liquid-liquid systems is assessed. The present lattice Boltzmann
simulations well reproduce the characteristics of predicted regimes, including
varicose breakup, sinuous breakup, and atomization.
PMID- 29347181
TI - Relationship between the size of a camphor-driven rotor and its angular velocity.
AB - We consider a rotor made of two camphor disks glued below the ends of a plastic
stripe. The disks are floating on a water surface and the plastic stripe does not
touch the surface. The system can rotate around a vertical axis located at the
center of the stripe. The disks dissipate camphor molecules. The driving momentum
comes from the nonuniformity of surface tension resulting from inhomogeneous
surface concentration of camphor molecules around the disks. We investigate the
stationary angular velocity as a function of rotor radius l. For large l the
angular velocity decreases for increasing l. At a specific value of l the angular
velocity reaches its maximum and, for short l it rapidly decreases. Such behavior
is confirmed by a simple numerical model. The model also predicts that there is a
critical rotor size below which it does not rotate. Within the introduced model
we analyze the type of this bifurcation.
PMID- 29347182
TI - Propulsion via flexible flapping in granular media.
AB - Biological locomotion in nature is often achieved by the interaction between a
flexible body and its surrounding medium. The interaction of a flexible body with
granular media is less understood compared with viscous fluids partially due to
its complex rheological properties. In this work, we explore the effect of
flexibility on granular propulsion by considering a simple mechanical model in
which a rigid rod is connected to a torsional spring that is under a displacement
actuation using a granular resistive force theory. Through a combined numerical
and asymptotic investigation, we characterize the propulsive dynamics of such a
flexible flapper in relation to the actuation amplitude and spring stiffness, and
we compare these dynamics with those observed in a viscous fluid. In addition, we
demonstrate that the maximum possible propulsive force can be obtained in the
steady propulsion limit with a finite spring stiffness and large actuation
amplitude. These results may apply to the development of synthetic locomotive
systems that exploit flexibility to move through complex terrestrial media.
PMID- 29347183
TI - Quantum dynamics of long-range interacting systems using the positive-P and gauge
P representations.
AB - We provide the necessary framework for carrying out stochastic positive-P and
gauge-P simulations of bosonic systems with long-range interactions. In these
approaches, the quantum evolution is sampled by trajectories in phase space,
allowing calculation of correlations without truncation of the Hilbert space or
other approximations to the quantum state. The main drawback is that the
simulation time is limited by noise arising from interactions. We show that the
long-range character of these interactions does not further increase the
limitations of these methods, in contrast to the situation for alternatives such
as the density matrix renormalization group. Furthermore, stochastic gauge
techniques can also successfully extend simulation times in the long-range
interaction case, by making using of parameters that affect the noise properties
of trajectories, without affecting physical observables. We derive essential
results that significantly aid the use of these methods: estimates of the
available simulation time, optimized stochastic gauges, a general form of the
characteristic stochastic variance, and adaptations for very large systems.
Testing the performance of particular drift and diffusion gauges for nonlocal
interactions, we find that, for small to medium systems, drift gauges are
beneficial, whereas for sufficiently large systems, it is optimal to use only a
diffusion gauge. The methods are illustrated with direct numerical simulations of
interaction quenches in extended Bose-Hubbard lattice systems and the excitation
of Rydberg states in a Bose-Einstein condensate, also without the need for the
typical frozen gas approximation. We demonstrate that gauges can indeed lengthen
the useful simulation time.
PMID- 29347184
TI - Boundary in the dynamic phase of globally coupled oscillatory and excitable
units.
AB - There is a crucial boundary between dynamic phase 1 and dynamic phase 2 of
globally coupled oscillatory and excitable units, where the mean field is
constant and oscillates in the former and the latter, respectively. This boundary
is theoretically derived here for a large population of dynamical units, each
having only a phase variable, where it is assumed that both the coupling strength
and the distribution width of bifurcation parameters are equally small. This
theory, which is applicable only if all or most of the units are intrinsically
oscillatory, is confirmed to agree with simulation results for two different
distribution densities.
PMID- 29347185
TI - Balancing specificity, sensitivity, and speed of ligand discrimination by zero
order ultraspecificity.
AB - Specific interactions between receptors and their target ligands in the presence
of nontarget ligands are crucial for biological processes such as T cell ligand
discrimination. To discriminate between the target and nontarget ligands, cells
have to increase specificity to the target ligands by amplifying the small
differences in affinity among ligands. In addition, sensitivity to the ligand
concentration and quick discrimination are also important to detect low amounts
of target ligands and facilitate fast cellular decision making after ligand
recognition. In this work we propose a mechanism for nonlinear specificity
amplification (ultraspecificity) based on zero-order saturating reactions, which
was originally proposed to explain nonlinear sensitivity amplification
(ultrasensitivity) to the ligand concentration. In contrast to the previously
proposed proofreading mechanisms that amplify the specificity by a multistep
reaction, our model can produce an optimal balance of specificity, sensitivity,
and quick discrimination. Furthermore, we show that a model for insensitivity to
a large number of nontarget ligands can be naturally derived from a model with
the zero-order ultraspecificity. The zero-order ultraspecificity, therefore, may
provide an alternative way to understand ligand discrimination from the viewpoint
of nonlinear properties in biochemical reactions.
PMID- 29347186
TI - Extreme event statistics in a drifting Markov chain.
AB - We analyze extreme event statistics of experimentally realized Markov chains with
various drifts. Our Markov chains are individual trajectories of a single atom
diffusing in a one-dimensional periodic potential. Based on more than 500
individual atomic traces we verify the applicability of the Sparre Andersen
theorem to our system despite the presence of a drift. We present detailed
analysis of four different rare-event statistics for our system: the
distributions of extreme values, of record values, of extreme value occurrence in
the chain, and of the number of records in the chain. We observe that, for our
data, the shape of the extreme event distributions is dominated by the underlying
exponential distance distribution extracted from the atomic traces. Furthermore,
we find that even small drifts influence the statistics of extreme events and
record values, which is supported by numerical simulations, and we identify cases
in which the drift can be determined without information about the underlying
random variable distributions. Our results facilitate the use of extreme event
statistics as a signal for small drifts in correlated trajectories.
PMID- 29347187
TI - Mean-field dynamics of a population of stochastic map neurons.
AB - We analyze the emergent regimes and the stimulus-response relationship of a
population of noisy map neurons by means of a mean-field model, derived within
the framework of cumulant approach complemented by the Gaussian closure
hypothesis. It is demonstrated that the mean-field model can qualitatively
account for stability and bifurcations of the exact system, capturing all the
generic forms of collective behavior, including macroscopic excitability,
subthreshold oscillations, periodic or chaotic spiking, and chaotic bursting
dynamics. Apart from qualitative analogies, we find a substantial quantitative
agreement between the exact and the approximate system, as reflected in matching
of the parameter domains admitting the different dynamical regimes, as well as
the characteristic properties of the associated time series. The effective model
is further shown to reproduce with sufficient accuracy the phase response curves
of the exact system and the assembly's response to external stimulation of finite
amplitude and duration.
PMID- 29347188
TI - Reply to "Comment on 'Flow of wet granular materials: A numerical study' ".
AB - In his Comment on our paper [Phys. Rev. E 92, 022201
(2015)10.1103/PhysRevE.92.022201], Chareyre criticizes, as inaccurate, the simple
approach we adopted to explain the strong enhancement of the quasistatic shear
strength of the material caused by capillary cohesion. He also observes that a
similar form of the "effective stress" approach, accounting for the capillary
shear stress, which we neglected, results in a quantitatively correct prediction
of this yield stress. We agree with these remarks, which we deem quite relevant
and valuable. We nevertheless point out that the initial approximation, despite
~25% errors on shear strength in the worst cases, provides a convenient estimate
of the Mohr-Coulomb cohesion of the material, which is directly related to the
coordination number. We argue that the effective stress assumption, despite its
surprising success in the range of states explored in Khamseh et al. [Phys. Rev.
E 92, 022201 (2015)10.1103/PhysRevE.92.022201], is bound to fail in strongly
cohesion-dominated material states.
PMID- 29347189
TI - Turing mechanism for homeostatic control of synaptic density during C. elegans
growth.
AB - We propose a mechanism for the homeostatic control of synapses along the ventral
cord of Caenorhabditis elegans during development, based on a form of Turing
pattern formation on a growing domain. C. elegans is an important animal model
for understanding cellular mechanisms underlying learning and memory. Our
mathematical model consists of two interacting chemical species, where one is
passively diffusing and the other is actively trafficked by molecular motors,
which switch between forward and backward moving states (bidirectional
transport). This differs significantly from the standard mechanism for Turing
pattern formation based on the interaction between fast and slow diffusing
species. We derive evolution equations for the chemical concentrations on a
slowly growing one-dimensional domain, and use numerical simulations to
demonstrate the insertion of new concentration peaks as the length increases.
Taking the passive component to be the protein kinase CaMKII and the active
component to be the glutamate receptor GLR-1, we interpret the concentration
peaks as sites of new synapses along the length of C. elegans, and thus show how
the density of synaptic sites can be maintained.
PMID- 29347190
TI - Exact phase boundaries and topological phase transitions of the XYZ spin chain.
AB - Within the block spin renormalization group, we give a very simple derivation of
the exact phase boundaries of the XYZ spin chain. First, we identify the Ising
order along x[over ] or y[over ] as attractive renormalization group fixed points
of the Kitaev chain. Then, in a global phase space composed of the anisotropy
lambda of the XY interaction and the coupling Delta of the
Deltasigma^{z}sigma^{z} interaction, we find that the above fixed points remain
attractive in the two-dimesional parameter space. We therefore classify the
gapped phases of the XYZ spin chain as: (1) either attracted to the Ising limit
of the Kitaev-chain, which in turn is characterized by winding number +/-1,
depending on whether the Ising order parameter is along x[over ] or y[over ]
directions; or (2) attracted to the charge density wave (CDW) phases of the
underlying Jordan-Wigner fermions, which is characterized by zero winding number.
We therefore establish that the exact phase boundaries of the XYZ model in
Baxter's solution indeed correspond to topological phase transitions. The
topological nature of the phase transitions of the XYZ model justifies why our
analytical solution of the three-site problem that is at the core of the present
renormalization group treatment is able to produce the exact phase boundaries of
Baxter's solution. We argue that the distribution of the winding numbers between
the three Ising phases is a matter of choice of the coordinate system, and
therefore the CDW-Ising phase is entitled to host appropriate form of zero modes.
We further observe that in the Kitaev-chain the renormalization group flow can be
cast into a geometric progression of a properly identified parameter. We show
that this new parameter is actually the size of the (Majorana) zero modes.
PMID- 29347191
TI - Time-reversal symmetry for systems in a constant external magnetic field.
AB - The time-reversal properties of charged systems in a constant external magnetic
field are reconsidered in this paper. We show that the evolution equations of the
system are invariant under a new symmetry operation that implies a new signature
property for time-correlation functions under time reversal. We then show how
these findings can be combined with a previously identified symmetry to
determine, for example, null components of the correlation functions of
velocities and currents and of the associated transport coefficients. These
theoretical predictions are illustrated by molecular dynamics simulations of
superionic AgI.
PMID- 29347192
TI - Endoreversible quantum heat engines in the linear response regime.
AB - We analyze general models of quantum heat engines operating a cycle of two
adiabatic and two isothermal processes. We use the quantum master equation for a
system to describe heat transfer current during a thermodynamic process in
contact with a heat reservoir, with no use of phenomenological thermal
conduction. We apply the endoreversibility description to such engine models
working in the linear response regime and derive expressions of the efficiency
and the power. By analyzing the entropy production rate along a single cycle, we
identify the thermodynamic flux and force that a linear relation connects. From
maximizing the power output, we find that such heat engines satisfy the tight
coupling condition and the efficiency at maximum power agrees with the Curzon
Ahlborn efficiency known as the upper bound in the linear response regime.
PMID- 29347193
TI - Pseudo-Hermitian anti-Hermitian ensemble of Gaussian matrices.
AB - It is shown that the ensemble of pseudo-Hermitian Gaussian matrices recently
introduced gives rise in a certain limit to an ensemble of anti-Hermitian
matrices whose eigenvalues have properties directly related to those of the
chiral ensemble of random matrices.
PMID- 29347194
TI - Comment on "Flow of wet granular materials: A numerical study".
AB - The effective stress model of Khamseh et al., Phys. Rev. E 92, 022201
(2015)PLEEE81539-375510.1103/PhysRevE.92.022201 is in semiquantitative agreement
with the shear stress in simulated steady state flow of a wet granular material.
Nonetheless, the predictions are increasingly biased at low normal pressure. The
approximation of the capillary stress by a spherical tensor in this model is a
sufficient cause of the prediction errors, as shown in this Comment. The re
examination reveals an excellent agreement between the data and the effective
stress expression formerly introduced for similar systems, further validating a
yet unexplained empirical result.
PMID- 29347195
TI - Floquet analysis of Kuznetsov-Ma breathers: A path towards spectral stability of
rogue waves.
AB - In the present work, we aim at taking a step towards the spectral stability
analysis of Peregrine solitons, i.e., wave structures that are used to emulate
extreme wave events. Given the space-time localized nature of Peregrine solitons,
this is a priori a nontrivial task. Our main tool in this effort will be the
study of the spectral stability of the periodic generalization of the Peregrine
soliton in the evolution variable, namely the Kuznetsov-Ma breather. Given the
periodic structure of the latter, we compute the corresponding Floquet
multipliers, and examine them in the limit where the period of the orbit tends to
infinity. This way, we extrapolate towards the stability of the limiting
structure, namely the Peregrine soliton. We find that multiple unstable modes of
the background are enhanced, yet no additional unstable eigenmodes arise as the
Peregrine limit is approached. We explore the instability evolution also in
direct numerical simulations.
PMID- 29347196
TI - Iterative control strategies for nonlinear systems.
AB - In this paper, we focus on the control of the mean-field equilibrium of nonlinear
networks of the Langevin type in the limit of small noise. Using iterative linear
approximations, we derive a formula that prescribes a control strategy in order
to displace the equilibrium state of a given system and remarkably find that the
control function has a "universal" form under certain physical conditions. This
result can be employed to define universal protocols useful, for example, in the
optimal work extraction from a given reservoir. Generalizations and limits of
application of the method are discussed.
PMID- 29347197
TI - Dynamical crossover in a stochastic model of cell fate decision.
AB - We study the asymptotic behaviors of stochastic cell fate decision between
proliferation and differentiation. We propose a model of a self-replicating
Langevin system, where cells choose their fate (i.e., proliferation or
differentiation) depending on local cell density. Based on this model, we propose
a scenario for multicellular organisms to maintain the density of cells (i.e.,
homeostasis) through finite-ranged cell-cell interactions. Furthermore, we
numerically show that the distribution of the number of descendant cells changes
over time, thus unifying the previously proposed two models regarding
homeostasis: the critical birth death process and the voter model. Our results
provide a general platform for the study of stochastic cell fate decision in
terms of nonequilibrium statistical mechanics.
PMID- 29347198
TI - Supercritical Gruneisen parameter and its universality at the Frenkel line.
AB - We study the thermomechanical properties of matter under extreme conditions deep
in the supercritical state, at temperatures exceeding the critical one by up to
four orders of magnitude. We calculate the Gruneisen parameter gamma and find
that on isochores it decreases with temperature from 3 to 1, depending on the
density. Our results indicate that from the perspective of thermomechanical
properties, the supercritical state is characterized by a wide range of gamma's
which includes solidlike values-an interesting finding in view of the common
perception of the supercritical state as being an intermediate state between
gases and liquids. We rationalize this result by considering the relative weights
of oscillatory and diffusive components of the supercritical system below the
Frenkel line. We also find that gamma is nearly constant at the Frenkel line
above the critical point and explain this universality in terms of the pressure
and temperature scaling of system properties along the lines where particle
dynamics changes qualitatively.
PMID- 29347199
TI - Single and double linear and nonlinear flatband chains: Spectra and modes.
AB - We report results of systematic analysis of various modes in the flatband
lattice, based on the diamond-chain model with the on-site cubic nonlinearity,
and its double version with the linear on-site mixing between the two lattice
fields. In the single-chain system, a full analysis is presented, first, for the
single nonlinear cell, making it possible to find all stationary states, viz.,
antisymmetric, symmetric, and asymmetric ones, including an exactly investigated
symmetry-breaking bifurcation of the subcritical type. In the nonlinear infinite
single-component chain, compact localized states (CLSs) are found in an exact
form too, as an extension of known compact eigenstates of the linear diamond
chain. Their stability is studied by means of analytical and numerical methods,
revealing a nontrivial stability boundary. In addition to the CLSs, various
species of extended states and exponentially localized lattice solitons of
symmetric and asymmetric types are also studied, by means of numerical
calculations and variational approximation. As a result, existence and stability
areas are identified for these modes. Finally, the linear version of the double
diamond chain is solved in an exact form, producing two split flatbands in the
system's spectrum.
PMID- 29347200
TI - Apparent slip of shear thinning fluid in a microchannel with a superhydrophobic
wall.
AB - The peculiarities of simple shear flow of shear thinning fluids over a
superhydrophobic wall consisting of a set of parallel gas-filled grooves and
solid stripes (domains with slip and stick boundary conditions) are studied
numerically. The Carreau-Yasuda model is used to provide further insight into the
problem of the slip behavior of non-Newtonian fluids having a decreasing
viscosity with a shear rate increase. This feature is demonstrated to cause a
nonlinear velocity profile leading to the apparent slip. The corresponding
transverse and longitudinal apparent slip lengths of a striped texture are found
to be noticeably larger than the respective effective slip lengths of Newtonian
liquids in microchannels of various thicknesses and surface fractions of the slip
domains. The viscosity distribution of the shear thinning fluid over the
superhydrophobic wall is carefully investigated to describe the mechanism of the
apparent slip. Nonmonotonic behavior of the apparent slip length as a function of
the applied shear rate is revealed. This important property of shear thinning
fluids is considered to be sensitive to the steepness of the viscosity flow
curve, thus providing a way to decrease considerably the flow resistance in
microchannels.
PMID- 29347201
TI - Stiffening thermal membranes by cutting.
AB - Two-dimensional crystalline membranes have recently been realized experimentally
in systems such as graphene and molybdenum disulfide, sparking a resurgence in
interest in their statistical properties. Thermal fluctuations can significantly
affect the effective mechanical properties of properly thermalized membranes,
renormalizing both bending rigidity and elastic moduli so that in particular they
become stiffer to bending than their bare bending rigidity would suggest. We use
molecular dynamics simulations to examine how the mechanical behavior of
thermalized two-dimensional clamped ribbons (cantilevers) depends on their
precise topology and geometry. We find that a simple slit smooths roughness as
measured by the variance of height fluctuations. This counterintuitive effect may
be due to the counterposed coupling of the lips of the slit to twist in the
intact regions of the ribbon.
PMID- 29347202
TI - Graphene as transmissive electrodes and aligning layers for liquid-crystal-based
electro-optic devices.
AB - In a conventional liquid crystal (LC) cell, polyimide layers are used to align
the LC homogeneously in the cell, and transmissive indium tin oxide (ITO)
electrodes are used to apply the electric field to reorient the LC along the
field. It is experimentally presented here that monolayer graphene films on the
two glass substrates can function concurrently as the LC aligning layers and the
transparent electrodes to fabricate an LC cell, without using the conventional
polyimide and ITO substrates. This replacement can effectively decrease the
thickness of all the alignment layers and electrodes from about 100 nm to less
than 1 nm. The interaction between LC and graphene through pi-pi electron
stacking imposes a planar alignment on the LC in the graphene-based cell-which is
verified using a crossed polarized microscope. The graphene-based LC cell
exhibits an excellent nematic director reorientation process from planar to
homeotropic configuration through the application of an electric field-which is
probed by dielectric and electro-optic measurements. Finally, it is shown that
the electro-optic switching is significantly faster in the graphene-based LC cell
than in a conventional ITO-polyimide LC cell.
PMID- 29347203
TI - Dynamical properties of the herding voter model with and without noise.
AB - Collective leadership and herding may arise in standard models of opinion
dynamics as an interplay of a strong separation of time scales within the
population and its hierarchical organization. Using the voter model as a simple
opinion formation model, we show that, in the herding phase, a group of agents
become effectively the leaders of the dynamics while the rest of the population
follow blindly their opinion. Interestingly, in some cases such herding dynamics
accelerates the time to consensus, which then becomes size independent or, on the
contrary, makes the consensus nearly impossible. These behaviors have important
consequences when an external noise is added to the system that makes consensus
(absorbing) states to disappear. We analyze this model, which shows an
interesting phase diagram, with a purely diffusive phase, a herding (or two
states) phase, and mixed phases where both behaviors are possible.
PMID- 29347204
TI - Magnetic-field-driven alteration in capillary filling dynamics in a narrow
fluidic channel.
AB - We investigated pressure-driven transport of an immiscible binary system,
constituted by two electrically conducting liquids, in a narrow fluidic channel
under the influence of an externally applied magnetic field. The surface
wettability was taken into account in the analysis considering that the walls of
the channel are chemically treated to obtain various predefined contact angles as
required for the study. Alterations in the capillary filling and wetting dynamics
in the channel stemming from a complex interplay among different forces acting
over the interface were investigated. It was shown that an alteration in the
strength of the magnetic field leads to an alteration in the dynamics of the
interface, which in turn, alters the filling and wetting dynamics nontrivially
upon interaction with the surface tension force due to the wetted walls of the
channel. It is emphasized that a contrast in properties of constituents of the
binary system gives rise to an alteration in the forces being applied across the
interface, leading to an intricate control over the filling and wetting dynamics
for a given flow configuration and an applied field strength. We believe that the
results obtained from this analysis may aid the design of microfluidic devices
used for multiphase transport.
PMID- 29347205
TI - Inferring network structure from cascades.
AB - Many physical, biological, and social phenomena can be described by cascades
taking place on a network. Often, the activity can be empirically observed, but
not the underlying network of interactions. In this paper we offer three
topological methods to infer the structure of any directed network given a set of
cascade arrival times. Our formulas hold for a very general class of models where
the activation probability of a node is a generic function of its degree and the
number of its active neighbors. We report high success rates for synthetic and
real networks, for several different cascade models.
PMID- 29347206
TI - Detection of time delays and directional interactions based on time series from
complex dynamical systems.
AB - Data-based and model-free accurate identification of intrinsic time delays and
directional interactions is an extremely challenging problem in complex dynamical
systems and their networks reconstruction. A model-free method with new scores is
proposed to be generally capable of detecting single, multiple, and distributed
time delays. The method is applicable not only to mutually interacting dynamical
variables but also to self-interacting variables in a time-delayed feedback loop.
Validation of the method is carried out using physical, biological, and
ecological models and real data sets. Especially, applying the method to air
pollution data and hospital admission records of cardiovascular diseases in Hong
Kong reveals the major air pollutants as a cause of the diseases and, more
importantly, it uncovers a hidden time delay (about 30-40 days) in the causal
influence that previous studies failed to detect. The proposed method is expected
to be universally applicable to ascertaining and quantifying subtle interactions
(e.g., causation) in complex systems arising from a broad range of disciplines.
PMID- 29347207
TI - Role of anchoring energy on the texture of cholesteric droplets: Finite-element
simulations and experiments.
AB - We present a numerical method to compute defect-free textures inside cholesteric
domains of arbitrary shape. This method has two interesting properties, namely a
robust and fast quadratic convergence to a local minimum of the Frank free
energy, thanks to a trust region strategy. We apply this algorithm to study the
texture of cholesteric droplets in coexistence with their isotropic liquid in two
cases: when the anchoring is planar and when it is tilted. In the first case, we
show how to determine the anchoring energy at the cholesteric-isotropic interface
from a study of the optical properties of droplets of different sizes oriented
with an electric field. This method is applied to the case of the liquid crystal
CCN-37. In the second case, we come back to the issue of the textural transition
as a function of the droplet radius between the double-twist droplets and the
banded droplets, observed for instance in cyanobiphenyl liquid crystals. We show
that, even if this transition is dominated by the saddle-splay Gauss constant
K_{4}, as was recently recognized by Yoshioka et al. [Soft Matter 12, 2400
(2016)1744-683X10.1039/C5SM02838H], the anchoring energy does also play an
important role that cannot be neglected.
PMID- 29347208
TI - Colloid-colloid hydrodynamic interaction around a bend in a quasi-one-dimensional
channel.
AB - We report a study of how a bend in a quasi-one-dimensional (q1D) channel
containing a colloid suspension at equilibrium that exhibits single-file particle
motion affects the hydrodynamic coupling between colloid particles. We observe
both structural and dynamical responses as the bend angle becomes more acute. The
structural response is an increasing depletion of particles in the vicinity of
the bend and an increase in the nearest-neighbor separation in the pair
correlation function for particles on opposite sides of the bend. The dynamical
response monitored by the change in the self-diffusion [D_{11}(x)] and coupling
[D_{12}(x)] terms of the pair diffusion tensor reveals that the pair separation
dependence of D_{12} mimics that of the pair correlation function just as in a
straight q1D channel. We show that the observed behavior is a consequence of the
boundary conditions imposed on the q1D channel: both the single-file motion and
the hydrodynamic flow must follow the channel around the bend.
PMID- 29347209
TI - Takeover times for a simple model of network infection.
AB - We study a stochastic model of infection spreading on a network. At each time
step a node is chosen at random, along with one of its neighbors. If the node is
infected and the neighbor is susceptible, the neighbor becomes infected. How many
time steps T does it take to completely infect a network of N nodes, starting
from a single infected node? An analogy to the classic "coupon collector" problem
of probability theory reveals that the takeover time T is dominated by extremal
behavior, either when there are only a few infected nodes near the start of the
process or a few susceptible nodes near the end. We show that for N?1, the
takeover time T is distributed as a Gumbel distribution for the star graph, as
the convolution of two Gumbel distributions for a complete graph and an Erdos
Renyi random graph, as a normal for a one-dimensional ring and a two-dimensional
lattice, and as a family of intermediate skewed distributions for d-dimensional
lattices with d>=3 (these distributions approach the convolution of two Gumbel
distributions as d approaches infinity). Connections to evolutionary dynamics,
cancer, incubation periods of infectious diseases, first-passage percolation, and
other spreading phenomena in biology and physics are discussed.
PMID- 29347210
TI - Eigenvector centrality for geometric and topological characterization of porous
media.
AB - Solving flow and transport through complex geometries such as porous media is
computationally difficult. Such calculations usually involve the solution of a
system of discretized differential equations, which could lead to extreme
computational cost depending on the size of the domain and the accuracy of the
model. Geometric simplifications like pore networks, where the pores are
represented by nodes and the pore throats by edges connecting pores, have been
proposed. These models, despite their ability to preserve the connectivity of the
medium, have difficulties capturing preferential paths (high velocity) and
stagnation zones (low velocity), as they do not consider the specific relations
between nodes. Nonetheless, network theory approaches, where a complex network is
a graph, can help to simplify and better understand fluid dynamics and transport
in porous media. Here we present an alternative method to address these issues
based on eigenvector centrality, which has been corrected to overcome the
centralization problem and modified to introduce a bias in the centrality
distribution along a particular direction to address the flow and transport
anisotropy in porous media. We compare the model predictions with millifluidic
transport experiments, which shows that, albeit simple, this technique is
computationally efficient and has potential for predicting preferential paths and
stagnation zones for flow and transport in porous media. We propose to use the
eigenvector centrality probability distribution to compute the entropy as an
indicator of the "mixing capacity" of the system.
PMID- 29347211
TI - Dependence of the configurational entropy on amorphous structures of a hard
sphere fluid.
AB - The free energy of a hard-sphere fluid for which the average energy is trivial
signifies how its entropy changes with packing. The packing eta_{f} at which the
free energy of the crystalline state becomes lower than that of the disordered
fluid state marks the freezing point. For packing fractions eta>eta_{f} of the
hard-sphere fluid, we use the modified weighted density functional approximation
to identify metastable free energy minima intermediate between uniform fluid and
crystalline states. The distribution of the sharply localized density profiles,
i.e., the inhomogeneous density field rho(x) characterizing the metastable state
is primarily described by a pair function g_{s}(eta/eta_{0}). eta_{0} is a
structural parameter such that for eta=eta_{0} the pair function is identical to
that for the Bernal random structure. The configurational entropy S_{c} of the
metastable hard-sphere fluid is calculated by subtracting the corresponding
vibrational entropy from the total entropy. The extrapolated S_{c} vanishes as
eta->eta_{K} and eta_{K} is in agreement with other works. The dependence of
eta_{K} on the structural parameter eta_{0} is obtained.
PMID- 29347212
TI - Theory of microphase separation in bidisperse chiral membranes.
AB - We present a Ginzburg-Landau theory of microphase separation in a bidisperse
chiral membrane consisting of rods of opposite handedness. This model system
undergoes a phase transition from an equilibrium state where the two components
are completely phase separated to a state composed of microdomains of a finite
size comparable to the twist penetration depth. Characterizing the phenomenology
using linear stability analysis and numerical studies, we trace the origin of the
discontinuous change in microdomain size that occurs during this phase transition
to a competition between the cost of creating an interface and the gain in twist
energy for small microdomains in which the twist penetrates deep into the center
of the domain.
PMID- 29347213
TI - Nonlinear dispersive waves in repulsive lattices.
AB - The propagation of nonlinear waves in a lattice of repelling particles is studied
theoretically and experimentally. A simple experimental setup is proposed,
consisting of an array of coupled magnetic dipoles. By driving harmonically the
lattice at one boundary, we excite propagating waves and demonstrate different
regimes of mode conversion into higher harmonics, strongly influenced by
dispersion and discreteness. The phenomenon of acoustic dilatation of the chain
is also predicted and discussed. The results are compared with the theoretical
predictions of the alpha-Fermi-Pasta-Ulam equation, describing a chain of masses
connected by nonlinear quadratic springs and numerical simulations. The results
can be extrapolated to other systems described by this equation.
PMID- 29347214
TI - Quantum Hamiltonian daemons: Unitary analogs of combustion engines.
AB - Hamiltonian daemons have recently been defined classically as small, closed
Hamiltonian systems which can exhibit secular energy transfer from high-frequency
to low-frequency degrees of freedom (steady downconversion), analogous to the
steady transfer of energy in a combustion engine from the high terahertz
frequencies of molecular excitations to the low kilohertz frequencies of piston
motion [L. Gilz, E. P. Thesing, and J. R. Anglin, Phys. Rev. E 94, 042127
(2016)2470-004510.1103/PhysRevE.94.042127]. Classical daemons achieve
downconversion within a small, closed system by exploiting nonlinear resonances;
the adiabatic theorem permits their operation but imposes nontrivial limitations
on their efficiency. Here we investigate a simple example of a quantum mechanical
daemon. In the correspondence regime it obeys similar efficiency limits to its
classical counterparts, but in the strongly quantum mechanical regime the daemon
operates in an entirely different manner. It maintains an engine-like behavior in
a distinctly quantum mechanical form: a weight is lifted at a steady average
speed through a long sequence of quantum jumps in momentum, at each of which a
quantum of fuel is consumed. The quantum daemon can cease downconversion at any
time through nonadiabatic Landau-Zener transitions, and continuing operation of
the quantum daemon is associated with steadily growing entanglement between fast
and slow degrees of freedom.
PMID- 29347215
TI - Optomechanical proposal for monitoring microtubule mechanical vibrations.
AB - Microtubules provide the mechanical force required for chromosome separation
during mitosis. However, little is known about the dynamic (high-frequency)
mechanical properties of microtubules. Here, we theoretically propose to control
the vibrations of a doubly clamped microtubule by tip electrodes and to detect
its motion via the optomechanical coupling between the vibrational modes of the
microtubule and an optical cavity. In the presence of a red-detuned strong pump
laser, this coupling leads to optomechanical-induced transparency of an optical
probe field, which can be detected with state-of-the art technology. The center
frequency and line width of the transparency peak give the resonance frequency
and damping rate of the microtubule, respectively, while the height of the peak
reveals information about the microtubule-cavity field coupling. Our method opens
the new possibilities to gain information about the physical properties of
microtubules, which will enhance our capability to design physical cancer
treatment protocols as alternatives to chemotherapeutic drugs.
PMID- 29347216
TI - Ordering phenomena in a heterostructure of frustrated and unfrustrated triangular
lattice Ising layers.
AB - We study critical and magnetic properties of a bilayer Ising system consisting of
two triangular planes A and B, with the antiferromagnetic (AF) coupling J_{A} and
the ferromagnetic (FM) one J_{B} for the respective layers, which are coupled by
the interlayer interaction J_{AB} by using Monte Carlo simulations. When J_{A}
and J_{B} are of the same order, the unfrustrated FM plane orders first at a high
temperature T_{c1}~J_{B}. The spontaneous FM order then exerts influence on the
other frustrated AF plane as an effective magnetic field, which subsequently
induces a ferrimagnetic order in this plane at low temperatures below T_{c2}.
When short-range order is developed in the AF plane while the influence of the FM
plane is still small, there appears a preemptive Berezinskii-Kosterlitz-Thouless
type pseudocritical crossover regime just above the ferrimagnetic phase
transition point, where the short-distance behavior up to a rather large length
scale exponentially diverging in ?J_{A}/T is controlled by a line of Gaussian
fixed points at T=0. In the crossover region, a continuous variation in the
effective critical exponent 4/9?eta^{eff}?1/2 is observed. The phase diagram by
changing the ratio J_{A}/J_{B} is also investigated.
PMID- 29347217
TI - Aging in the three-dimensional random-field Ising model.
AB - We studied the nonequilibrium aging behavior of the random-field Ising model in
three dimensions for various values of the disorder strength. This allowed us to
investigate how the aging behavior changes across the ferromagnetic-paramagnetic
phase transition. We investigated a large system size of N=256^{3} spins and up
to 10^{8} Monte Carlo sweeps. To reach these necessary long simulation times, we
employed an implementation running on Intel Xeon Phi coprocessors, reaching
single-spin-flip times as short as 6 ps. We measured typical correlation
functions in space and time to extract a growing length scale and corresponding
exponents.
PMID- 29347218
TI - Effect of particle-size dynamics on properties of dense spongy-particle systems:
Approach towards equilibrium.
AB - Open-porous deformable particles, often envisaged as sponges, are ubiquitous in
biological and industrial systems (e.g., casein micelles in dairy products and
microgels in cosmetics). The rich behavior of these suspensions is owing to the
elasticity of the supporting network of the particle, and the viscosity of
permeating solvent. Therefore, the rate-dependent size change of these particles
depends on their structure, i.e., the permeability. This work aims at
investigating the effect of the particle-size dynamics and the underlying
particle structure, i.e., the particle permeability, on the transient and long
time behavior of suspensions of spongy particles in the absence of applied
deformation, using the dynamic two-scale model developed by Hutter et al. [Farad.
Discuss. 158, 407 (2012)1359-664010.1039/c2fd20025b]. In the high-density limit,
the transient behavior is found to be accelerated by the particle-size dynamics,
even at average size changes as small as 1%. The accelerated dynamics is
evidenced by (i) the higher short-time diffusion coefficient as compared to
elastic-particle systems and (ii) the accelerated formation of the stable fcc
crystal structure. Furthermore, after long times, the particle-size dynamics of
spongy particles is shown to result in lower stationary values of the energy and
normal stresses as compared to elastic-particle systems. This dependence of the
long-time behavior of these systems on the permeability, that essentially is a
transport coefficient and hence must not affect the equilibrium properties,
confirms that full equilibration has not been reached.
PMID- 29347219
TI - Transport and diffusion properties of Brownian particles powered by a rotating
wheel.
AB - Diffusion and rectification of Brownian particles powered by a rotating wheel are
numerically investigated in a two-dimensional channel. The nonequilibrium driving
comes from the rotating wheel, which can break thermodynamical equilibrium and
induce the directed transport in an asymmetric potential. It is found that the
direction of the transport along the potential is determined by the asymmetry of
the potential and the position of the wheel. The average velocity is a peaked
function of the angular speed (or the diffusion coefficient) and the position of
the peak shifts to large angular speed (or diffusion coefficient) when the
diffusion coefficient (or the angular speed) increases. There exists an optimal
angular speed (or diffusion coefficient) at which the effective diffusion
coefficient takes its maximal value. Remarkably, the giant acceleration of
diffusion is observed by suitably adjusting the system parameters. The parameters
corresponding to the maximum effective diffusion coefficient are not the same as
the parameters at which average velocity is maximum.
PMID- 29347220
TI - Geometrical properties of rigid frictionless granular packings as a function of
particle size and shape.
AB - Three-dimensional discrete numerical simulation is used to investigate the
properties of close-packed frictionless granular assemblies as a function of
particle polydispersity and shape. Unlike some experimental results, simulations
show that disordered packings of pinacoids (eight-face convex polyhedra) achieve
higher solid fraction values than amorphous packings of spherical or rounded
particles, thus fulfilling the analog of Ulam's conjecture stated by Jiao and co
workers for random packings [Y. Jiao and S. Torquato, Phys. Rev. E 84, 041309
(2011)PLEEE81539-375510.1103/PhysRevE.84.041309]. This seeming discrepancy
between experimental and numerical results is believed to result from
difficulties in overcoming inter particle friction through experimental
densification processes. Moreover, solid fraction is shown to increase further
with bidispersity and peak when the volume proportion of small particles reaches
30%. Contrarily, substituting up to 50% of flat pinacoids for isometric ones
yields solid fraction decrease, especially when flat particles are also
elongated. Nevertheless, particle shape seems to play a minor role in packing
solid fraction compared to polydispersity. Additional investigations focused on
the packing microstructure confirm that pinacoid packings fulfill the isostatic
conjecture and that they are free of order except beyond 30% to 50% of flat or
flat-elongated polyhedra in the packing. This order increase progressively takes
the form of a nematic phase caused by the reorientation of flat or flat-elongated
particles to minimize the packing potential energy. Simultaneously, this
reorientation seems to increase the solid fraction value slightly above the
maximum achieved by monodisperse isometric pinacoids, as well as the coordination
number. Finally, partial substitution of elongated pinacoids for isometric ones
has limited effect on packing solid fraction or order.
PMID- 29347221
TI - Production rate of the system-bath mutual information.
AB - When an open system comes into contact with several thermal baths, the entropy
produced by the irreversible processes (dS_{i}=dS-?_{alpha} dQ_{alpha}/T_{alpha})
keeps increasing, and this entropy production rate is always non-negative.
However, when the system comes into contact with nonthermal baths containing
quantum coherence or squeezing, this entropy production formula does not apply.
In this paper, we study the increasing rate of mutual information between an open
system and its environment. In the case of canonical thermal baths, we prove that
this mutual information production rate could return exactly to the previous
entropy production rate. Furthermore, we study an example of a single boson mode
that comes into contact with multiple squeezed thermal baths, where the
conventional entropy production rate does not apply, and we find that this mutual
information production rate remains non-negative, which indicates a monotonic
increase in the correlation between the system and its environment.
PMID- 29347222
TI - Extremal-point density of scaling processes: From fractional Brownian motion to
turbulence in one dimension.
AB - In recent years several local extrema-based methodologies have been proposed to
investigate either the nonlinear or the nonstationary time series for scaling
analysis. In the present work, we study systematically the distribution of the
local extrema for both synthesized scaling processes and turbulent velocity data
from experiments. The results show that for the fractional Brownian motion (fBm)
without intermittency correction the measured extremal-point-density (EPD) agrees
well with a theoretical prediction. For a multifractal random walk (MRW) with the
lognormal statistics, the measured EPD is independent of the intermittency
parameter MU, suggesting that the intermittency correction does not change the
distribution of extremal points but changes the amplitude. By introducing a
coarse-grained operator, the power-law behavior of these scaling processes is
then revealed via the measured EPD for different scales. For fBm the scaling
exponent xi(H) is found to be xi(H)=H, where H is Hurst number, while for MRW
xi(MU) shows a linear relation with the intermittency parameter MU. Such EPD
approach is further applied to the turbulent velocity data obtained from a wind
tunnel flow experiment with the Taylor scale lambda-based Reynolds number
Re_{lambda}=720, and a turbulent boundary layer with the momentum thickness theta
based Reynolds number Re_{theta}=810. A scaling exponent xi?0.37 is retrieved for
the former case. For the latter one, the measured EPD shows clearly four regimes,
which agrees well with the corresponding sublayer structures inside the turbulent
boundary layer.
PMID- 29347223
TI - Metal nanospheres under intense continuous-wave illumination: A unique case of
nonperturbative nonlinear nanophotonics.
AB - We show that the standard perturbative (i.e., cubic) description of the thermal
nonlinear response of a single metal nanosphere to intense continuous-wave (CW)
illumination is sufficient only for a temperature rise of up to 100 degrees above
room temperature. Beyond this regime, the slowing down of the temperature rise
requires a nonperturbative description of the nonlinear response, even though the
permittivity is linearly dependent on the temperature and despite the deep
subwavelength effective propagation distances involved. Using experimental data,
we show that, generically, the increase of the imaginary part of the metal
permittivity dominates the increase of the host permittivity as well as the
resonance shift due to the joint changes to the real parts of the metal and host.
Thus, the main nonlinear effect is a decrease of the quality factor of the
resonance. We further analyze the relative importance of the various
contributions to the temperature rise and thermal nonlinearity, compare the
nonlinearity of Au and Ag, demonstrate the potential effect of the nanoparticle
morphology, and show that although the thermo-optical nonlinearity of the host
typically plays a minor role, its thermal conductivity and its temperature
dependence is important. Finally, we discuss the differences between CW and
ultrafast thermal nonlinearities.
PMID- 29347224
TI - Spreading law of non-Newtonian power-law liquids on a spherical substrate by an
energy-balance approach.
AB - The spreading of a cap-shaped spherical droplet of non-Newtonian power-law
liquids, both shear-thickening and shear-thinning liquids, that completely wet a
spherical substrate is theoretically investigated in the capillary-controlled
spreading regime. The crater-shaped droplet model with the wedge-shaped meniscus
near the three-phase contact line is used to calculate the viscous dissipation
near the contact line. Then the energy balance approach is adopted to derive the
equation that governs the evolution of the contact line. The time evolution of
the dynamic contact angle theta of a droplet obeys a power law theta~t^{-alpha}
with the spreading exponent alpha, which is different from Tanner's law for
Newtonian liquids and those for non-Newtonian liquids on a flat substrate.
Furthermore, the line-tension dominated spreading, which could be realized on a
spherical substrate for late-stage of spreading when the contact angle becomes
low and the curvature of the contact line becomes large, is also investigated.
PMID- 29347225
TI - First-principles equation of state and shock compression predictions of warm
dense hydrocarbons.
AB - We use path integral Monte Carlo and density functional molecular dynamics to
construct a coherent set of equations of state (EOS) for a series of hydrocarbon
materials with various C:H ratios (2:1, 1:1, 2:3, 1:2, and 1:4) over the range of
0.07-22.4gcm^{-3} and 6.7*10^{3}-1.29*10^{8}K. The shock Hugoniot curve derived
for each material displays a single compression maximum corresponding to K-shell
ionization. For C:H = 1:1, the compression maximum occurs at 4.7-fold of the
initial density and we show radiation effects significantly increase the shock
compression ratio above 2 Gbar, surpassing relativistic effects. The single
peaked structure of the Hugoniot curves contrasts with previous work on higher-Z
plasmas, which exhibit a two-peak structure corresponding to both K- and L-shell
ionization. Analysis of the electronic density of states reveals that the change
in Hugoniot structure is due to merging of the L-shell eigenstates in carbon,
while they remain distinct for higher-Z elements. Finally, we show that the
isobaric-isothermal linear mixing rule for carbon and hydrogen EOS is a
reasonable approximation with errors better than 1% for stellar-core conditions.
PMID- 29347226
TI - Diffusion in time-dependent random media and the Kardar-Parisi-Zhang equation.
AB - Although time-dependent random media with short-range correlations lead to
(possibly biased) normal tracer diffusion, anomalous fluctuations occur away from
the most probable direction. This was pointed out recently in one-dimensional
(1D) lattice random walks, where statistics related to the 1D Kardar-Parisi-Zhang
(KPZ) universality class, i.e., the Gaussian unitary ensemble Tracy-Widom
distribution, were shown to arise. Here, we provide a simple picture for this
correspondence, directly in the continuum, which allows one to study arbitrary
space dimensions and to predict a variety of universal distributions. In d=1, we
predict and verify numerically the emergence of the Gaussian orthogonal ensemble
Tracy-Widom distribution for fluctuations of the transition probability. In d=3,
we predict a phase transition from Gaussian fluctuations to three-dimensional KPZ
type fluctuations as the bias is increased. We predict KPZ universal
distributions for the arrival time of a first particle from a cloud diffusing in
such media.
PMID- 29347227
TI - Thomas-Fermi simulations of dense plasmas without pseudopotentials.
AB - The Thomas-Fermi model for warm and hot dense matter is widely used to predict
material properties such as the equation of state. However, for practical reasons
current implementations use pseudopotentials for the electron-nucleus interaction
instead of the bare Coulomb potential. This complicates the calculation and
quantities such as free energy cannot be converged with respect to the
pseudopotential parameters. We present a method that retains the bare Coulomb
potential for the electron-nucleus interaction and does not use pseudopotentials.
We demonstrate that accurate free energies are obtained by checking variational
consistency. Examples for aluminum and iron plasmas are presented.
PMID- 29347228
TI - Dynamics of spinning particle pairs in a single-layer complex plasma crystal.
AB - Spontaneous formation of spinning pairs of particles, or torsions, is studied in
a single-layer complex plasma crystal by reducing the discharge power at constant
neutral gas pressure. At higher gas pressures, torsions spontaneously form below
a certain power threshold. Further reduction of the discharge power leads to the
formation of multiple torsions. However, at lower gas pressures the torsion
formation is preceded by mode-coupling instability (MCI). The crystal dynamics
are studied with the help of the fluctuation spectra of crystal particles' in
plane velocities. Surprisingly, the spectra of the crystal with torsions and MCI
are rather similar and contain hot spots at similar locations on the (k,omega)
plane, despite very different appearances of the respective particle
trajectories. The torsion rotation speed is close (slightly below) to the maximum
frequency of the in-plane compressional mode. When multiple torsions form, their
rotation speeds are distributed in a narrow range slightly below the maximum
frequency.
PMID- 29347229
TI - Phase diagram and criticality of the two-dimensional prisoner's dilemma model.
AB - The stationary states of the prisoner's dilemma model are studied on a square
lattice taking into account the role of a noise parameter in the decision-making
process. Only first neighboring players-defectors and cooperators-are considered
in each step of the game. Through Monte Carlo simulations we determined the phase
diagrams of the model in the plane noise versus the temptation to defect for a
large range of values of the noise parameter. We observed three phases:
cooperators and defectors absorbing phases, and a coexistence phase between them.
The phase transitions as well as the critical exponents associated with them were
determined using both static and dynamical scaling laws.
PMID- 29347230
TI - Detecting unstable periodic orbits in chaotic time series using synchronization.
AB - An alternative approach of detecting unstable periodic orbits in chaotic time
series is proposed using synchronization techniques. A master-slave
synchronization scheme is developed, in which the chaotic system drives a system
of harmonic oscillators through a proper coupling condition. The proposed scheme
is designed so that the power of the coupling signal exhibits notches that drop
to zero once the system approaches an unstable orbit yielding an explicit
indication of the presence of a periodic motion. The results shows that the
proposed approach is particularly suitable in practical situations, where the
time series is short and noisy, or it is obtained from high-dimensional chaotic
systems.
PMID- 29347231
TI - Reconstructing networks of pulse-coupled oscillators from spike trains.
AB - We present an approach for reconstructing networks of pulse-coupled neuronlike
oscillators from passive observation of pulse trains of all nodes. It is assumed
that units are described by their phase response curves and that their phases are
instantaneously reset by incoming pulses. Using an iterative procedure, we
recover the properties of all nodes, namely their phase response curves and
natural frequencies, as well as strengths of all directed connections.
PMID- 29347232
TI - Continuous-time random walk under time-dependent resetting.
AB - Continuous-time random walks of a particle that is randomly reset to an initial
position are considered. The distribution of the waiting time between the reset
events is represented as a sum of an arbitrary number of exponentials. The
governing equation of this stochastic process is established. The mean first
passage time to a particular position is calculated. It is shown that anomalous
subdiffusion has a significant impact on the shape of the stationary state.
PMID- 29347233
TI - Dynamics and energy spectra of aperiodic discrete-time quantum walks.
AB - We investigate the role of different aperiodic sequences in the dynamics of
single quantum particles in discrete space and time. For this we consider three
aperiodic sequences, namely, the Fibonacci, Thue-Morse, and Rudin-Shapiro
sequences, as examples of tilings the diffraction spectra of which have pure
point, singular continuous, and absolutely continuous support, respectively. Our
interest is to understand how the order, intrinsically introduced by the
deterministic rule used to generate the aperiodic sequences, is reflected in the
dynamical properties of the quantum system. For this system we consider a single
particle undergoing a discrete-time quantum walk (DTQW), where the aperiodic
sequences are used to distribute the coin operations at different lattice
positions (inhomogeneous DTQW) or by applying the same coin operation at all
lattice sites at a given time but choosing different coin operation at each time
step according to the chosen aperiodic sequence (time dependent DTQW). We study
the energy spectra and the spreading of an initially localized wave packet for
different cases, finding that in the case of Fibonacci and Thue-Morse tilings the
system is superdiffusive, whereas in the Rudin-Shapiro case it is strongly
subdiffusive. Trying to understand this behavior in terms of the energy spectra,
we look at the survival amplitude as a function of time. By means of the echo we
present strong evidence that, although the three orderings are very different as
evidenced by their diffraction spectra, the energy spectra are all singular
continuous except for the inhomogeneous DTQW with the Rudin-Shapiro sequence
where it is discrete. This is in agreement with the observed strong localization
both in real space and in the Hilbert space. Our paper is particularly
interesting because quantum walks can be engineered in laboratories by means of
ultracold gases or in optical waveguides, and therefore would be a perfect
playground to study singular continuous energy spectra in a completely controlled
quantum setup.
PMID- 29347234
TI - Pace and patterns of magnetic swimmers in a billiard pool.
AB - We experimentally investigate magnetic surface swimmers on water. These objects
self-assemble from ferromagnetic microparticles and a nonmagnetic disk. They are
floating on the liquid surface due to interface tension and move under the
influence of a harmonically oscillating homogeneous magnetic field oriented
vertically, which is distinguished by its amplitude and frequency. The speed of
the surface swimmers strongly depends on these parameters. The functional
dependencies between speed and amplitude and between speed and frequency are
investigated by independently varying both control parameters. In the first case,
the data obtained are in good agreement with the predicted scaling while there
are some deviations in the latter case. Moreover, due to the interplay between
the surface bound swimmers and the ascending liquid meniscus at the edge of the
experimental vessel, different dynamics can be realized. We observe periodic and
quasiperiodic trajectories in a circular vessel and aperiodic trajectories in a
vessel shaped like a Bunimovich stadium.
PMID- 29347235
TI - Ballistic aggregation in systems of inelastic particles: Cluster growth,
structure, and aging.
AB - We study far-from-equilibrium dynamics in models of freely cooling granular gas
and ballistically aggregating compact clusters. For both the cases, from event
driven molecular dynamics simulations, we have presented detailed results on
structure and dynamics in space dimensions d=1 and 2. Via appropriate analyses it
has been confirmed that the ballistic aggregation mechanism applies in d=1
granular gases as well. Aging phenomena for this mechanism, in both the
dimensions, have been studied via the two-time density autocorrelation function.
This quantity is demonstrated to exhibit scaling property similar to that in the
standard phase transition kinetics. The corresponding functional forms have been
quantified and the outcomes have been discussed in connection with the structural
properties. Our results on aging establish a more complete equivalence between
the granular gas and the ballistic aggregation models in d=1.
PMID- 29347236
TI - Importance-sampling computation of statistical properties of coupled oscillators.
AB - We introduce and implement an importance-sampling Monte Carlo algorithm to study
systems of globally coupled oscillators. Our computational method efficiently
obtains estimates of the tails of the distribution of various measures of
dynamical trajectories corresponding to states occurring with (exponentially)
small probabilities. We demonstrate the general validity of our results by
applying the method to two contrasting cases: the driven-dissipative Kuramoto
model, a paradigm in the study of spontaneous synchronization; and the
conservative Hamiltonian mean-field model, a prototypical system of long-range
interactions. We present results for the distribution of the finite-time Lyapunov
exponent and a time-averaged order parameter. Among other features, our results
show most notably that the distributions exhibit a vanishing standard deviation
but a skewness that is increasing in magnitude with the number of oscillators,
implying that nontrivial asymmetries and states yielding rare or atypical values
of the observables persist even for a large number of oscillators.
PMID- 29347237
TI - Linear and nonlinear response of the Vlasov system with nonintegrable
Hamiltonian.
AB - Linear and nonlinear response formulas taking into account all Casimir invariants
are derived without use of angle-action variables of a single-particle (mean
field) Hamiltonian. This article deals mainly with the Vlasov system in a
spatially inhomogeneous quasistationary state whose associating single-particle
Hamiltonian is not integrable and has only one integral of the motion, the
Hamiltonian itself. The basic strategy is to restrict the form of perturbation so
that it keeps Casimir invariants within a linear order, and the single particle's
probabilistic density function is smooth with respect to the single particle's
Hamiltonian. The theory is applied for a spatially two-dimensional system and is
confirmed by numerical simulations. A nonlinear response formula is also derived
in a similar manner.
PMID- 29347238
TI - Cascade replication of dissipative solitons.
AB - We report a new effect of a cascade replication of dissipative solitons from a
single one. It is discussed in the framework of a common model based on the one
dimensional cubic-quintic complex Ginzburg-Landau equation in which an additional
linear term is introduced to account the perturbation from a particular potential
of externally applied force. The effect is demonstrated on the light beams
propagating through a planar waveguide. The waveguide consists of a nonlinear
layer able to guide dissipative solitons and a magneto-optic substrate. In the
waveguide an externally applied force is considered to be an inhomogeneous
magnetic field which is induced by modulated electric currents flowing along a
set of conducting wires adjusted on the top of the waveguide.
PMID- 29347239
TI - Stochastic and information-thermodynamic structures of population dynamics in a
fluctuating environment.
AB - Adaptation in a fluctuating environment is a process of fueling environmental
information to gain fitness. Living systems have gradually developed strategies
for adaptation from random and passive diversification of the phenotype to more
proactive decision making, in which environmental information is sensed and
exploited more actively and effectively. Understanding the fundamental relation
between fitness and information is therefore crucial to clarify the limits and
universal properties of adaptation. In this work, we elucidate the underlying
stochastic and information-thermodynamic structure in this process, by deriving
causal fluctuation relations (FRs) of fitness and information. Combined with a
duality between phenotypic and environmental dynamics, the FRs reveal the limit
of fitness gain, the relation of time reversibility with the achievability of the
limit, and the possibility and condition for gaining excess fitness due to
environmental fluctuation. The loss of fitness due to causal constraints and the
limited capacity of real organisms is shown to be the difference between time
forward and time-backward path probabilities of phenotypic and environmental
dynamics. Furthermore, the FRs generalize the concept of the evolutionary stable
state (ESS) for fluctuating environment by giving the probability that the
optimal strategy on average can be invaded by a suboptimal one owing to rare
environmental fluctuation. These results clarify the information-thermodynamic
structures in adaptation and evolution.
PMID- 29347240
TI - Social contagions on weighted networks.
AB - We investigate critical behaviors of a social contagion model on weighted
networks. An edge-weight compartmental approach is applied to analyze the
weighted social contagion on strongly heterogenous networks with skewed degree
and weight distributions. We find that degree heterogeneity cannot only alter the
nature of contagion transition from discontinuous to continuous but also can
enhance or hamper the size of adoption, depending on the unit transmission
probability. We also show that the heterogeneity of weight distribution always
hinders social contagions, and does not alter the transition type.
PMID- 29347241
TI - Viscoinertial regime of immersed granular flows.
AB - By means of extensive coupled molecular dynamics-lattice Boltzmann simulations,
accounting for grain dynamics and subparticle resolution of the fluid phase, we
analyze steady inertial granular flows sheared by a viscous fluid. We show that,
for a broad range of system parameters (shear rate, confining stress, fluid
viscosity, and relative fluid-grain density), the frictional strength and packing
fraction can be described by a modified inertial number incorporating the fluid
effect. In a dual viscous description, the effective viscosity diverges as the
inverse square of the difference between the packing fraction and its jamming
value, as observed in experiments. We also find that the fabric and force
anisotropies extracted from the contact network are well described by the
modified inertial number, thus providing clear evidence for the role of these key
structural parameters in dense suspensions.
PMID- 29347242
TI - Multi-phase-field model for surface and phase-boundary diffusion.
AB - The multi-phase-field approach is generalized to treat capillarity-driven
diffusion parallel to the surfaces and phase boundaries, i.e., the boundaries
between a condensed phase and its vapor and the boundaries between two or
multiple condensed phases. The effect of capillarity is modeled via curvature
dependence of the chemical potential whose gradient gives rise to diffusion. The
model is used to study thermal grooving on the surface of a polycrystalline body.
Decaying oscillations of the surface profile during thermal grooving, postulated
by Hillert long ago but reported only in few studies so far, are observed and
discussed. Furthermore, annealing of multi-nanoclusters on a deformable free
surface is investigated using the proposed model. Results of these simulations
suggest that the characteristic craterlike structure with an elevated perimeter,
observed in recent experiments, is a transient nonequilibrium state during the
annealing process.
PMID- 29347243
TI - Analytical scalings of the linear Richtmyer-Meshkov instability when a
rarefaction is reflected.
AB - The Richtmyer-Meshkov instability for the case of a reflected rarefaction is
studied in detail following the growth of the contact surface in the linear
regime and providing explicit analytical expressions for the asymptotic
velocities in different physical limits. This work is a continuation of the
similar problem when a shock is reflected [Phys. Rev. E 93, 053111 (2016)1539
375510.1103/PhysRevE.93.053111]. Explicit analytical expressions for the
asymptotic normal velocity of the rippled surface (deltav_{i}^{infinity}) are
shown. The known analytical solution of the perturbations growing inside the
rarefaction fan is coupled to the pressure perturbations between the transmitted
shock front and the rarefaction trailing edge. The surface ripple growth
(psi_{i}) is followed from t=0+ up to the asymptotic stage inside the linear
regime. As in the shock reflected case, an asymptotic behavior of the form
psi_{i}(t)?psi_{infinity}+deltav_{i}^{infinity}t is observed, where
psi_{infinity} is an asymptotic ordinate to the origin. Approximate expressions
for the asymptotic velocities are given for arbitrary values of the shock Mach
number. The asymptotic velocity field is calculated at both sides of the contact
surface. The kinetic energy content of the velocity field is explicitly
calculated. It is seen that a significant part of the motion occurs inside a
fluid layer very near the material surface in good qualitative agreement with
recent simulations. The important physical limits of weak and strong shocks and
high and low preshock density ratio are also discussed and exact Taylor
expansions are given. The results of the linear theory are compared to
simulations and experimental work [R. L. Holmes et al., J. Fluid Mech. 389, 55
(1999)JFLSA70022-112010.1017/S0022112099004838; C. Mariani et al., Phys. Rev.
Lett. 100, 254503 (2008)PRLTAO0031-900710.1103/PhysRevLett.100.254503]. The
theoretical predictions of deltav_{i}^{infinity} and psi_{infinity} show good
agreement with the experimental and numerical reported values.
PMID- 29347244
TI - Marginally compact fractal trees with semiflexibility.
AB - We study marginally compact macromolecular trees that are created by means of two
different fractal generators. In doing so, we assume Gaussian statistics for the
vectors connecting nodes of the trees. Moreover, we introduce bond-bond
correlations that make the trees locally semiflexible. The symmetry of the
structures allows an iterative construction of full sets of eigenmodes
(notwithstanding the additional interactions that are present due to
semiflexibility constraints), enabling us to get physical insights about the
trees' behavior and to consider larger structures. Due to the local stiffness,
the self-contact density gets drastically reduced.
PMID- 29347245
TI - Kinetic Ising models with various single-spin-flip dynamics on quenched and
annealed random regular graphs.
AB - We investigate a kinetic Ising model with several single-spin-flip dynamics
(including Metropolis and heat bath) on quenched and annealed random regular
graphs. As expected, on the quenched structures all proposed algorithms reproduce
the same results since the conditions for the detailed balance and the Boltzmann
distribution in an equilibrium are satisfied. However, on the annealed graphs the
situation is far less clear-the network annealing disturbs the equilibrium moving
the system away from it. Consequently, distinct dynamics lead to different steady
states. We show that some algorithms are more resistant to the annealed disorder,
which causes only small quantitative changes in the model behavior. On the other
hand, there are dynamics for which the influence of annealing on the system is
significant, and qualitative changes arise like switching the type of phase
transition from a continuous to a discontinuous one. We try to identify features
of the proposed dynamics which are responsible for the above phenomenon.
PMID- 29347246
TI - Social contagion with degree-dependent thresholds.
AB - We investigate opinion spreading by a threshold model in a situation in which the
influence of people is heterogeneously distributed. We assume that there is a
coupling between the influence of an individual (measured by the out-degree) and
the threshold for accepting a new opinion or habit. We find that if the coupling
is strongly positive, the final state of the system will be a mix of different
opinions. Otherwise, it will converge to a consensus state. This phenomenon
cannot simply be explained as a phase transition, but it is a combined effect of
mechanisms and their relative dominance in different regions of parameter space.
PMID- 29347247
TI - Multivalent ligand-receptor-mediated interaction of small filled vesicles with a
cellular membrane.
AB - The ligand-receptor-mediated contacts of small sub-100-nm-sized lipid vesicles
(or nanoparticles) with the cellular membrane are of interest in the contexts of
cell-to-cell communication, endocytosis of membrane-coated virions, and drug
(RNA) delivery. In all these cases, the interior of vesicles is filled by
biologically relevant content. Despite the diversity of such systems, the
corresponding ligand-receptor interaction possesses universal features. One of
them is that the vesicle-membrane contacts can be accompanied by the
redistribution of ligands and receptors between the contact and contact-free
regions. In particular, the concentrations of ligands and receptors may become
appreciably higher in the contact regions and their composition may there be
different compared to that in the suspended state in the solution. A statistical
model presented herein describes the corresponding distribution of various
ligands and receptors and allows one to calculate the related change of the free
energy with variation of the vesicle-engulfment extent. The results obtained are
used to clarify the necessary conditions for the vesicle-assisted pathway of drug
delivery.
PMID- 29347248
TI - Transition probability generating function of a transitionless quantum parametric
oscillator.
AB - The transitionless tracking (TT) algorithm enables the exact tracking of quantum
adiabatic dynamics in an arbitrary short time by adding a counterdiabatic
Hamiltonian to the original adiabatic Hamiltonian. By applying Husimi's method
originally developed for a quantum parametric oscillator (QPO) to the
transitionless QPO achieved using the TT algorithm, we obtain the transition
probability generating function with a time-dependent parameter constituted with
solutions of the corresponding classical parametric oscillator (CPO). By
obtaining the explicit solutions of this CPO using the phase-amplitude method, we
find that the time-dependent parameter can be reduced to the frequency ratio
between the Hamiltonians without and with the counterdiabatic Hamiltonian, from
which we can easily characterize the result achieved by the TT algorithm. We
illustrate our theory by showing the trajectories of the CPO on the classical
phase space, which elucidate the effect of the counterdiabatic Hamiltonian of the
QPO.
PMID- 29347249
TI - Calculating how long it takes for a diffusion process to effectively reach steady
state without computing the transient solution.
AB - Mathematically, it takes an infinite amount of time for the transient solution of
a diffusion equation to transition from initial to steady state. Calculating a
finite transition time, defined as the time required for the transient solution
to transition to within a small prescribed tolerance of the steady-state
solution, is much more useful in practice. In this paper, we study estimates of
finite transition times that avoid explicit calculation of the transient solution
by using the property that the transition to steady state defines a cumulative
distribution function when time is treated as a random variable. In total, three
approaches are studied: (i) mean action time, (ii) mean plus one standard
deviation of action time, and (iii) an approach we derive by approximating the
large time asymptotic behavior of the cumulative distribution function. Our
approach leads to a simple formula for calculating the finite transition time
that depends on the prescribed tolerance delta and the (k-1)th and kth moments
(k>=1) of the distribution. Results comparing exact and approximate finite
transition times lead to two key findings. First, although the first two
approaches are useful at characterizing the time scale of the transition, they do
not provide accurate estimates for diffusion processes. Second, the new approach
allows one to calculate finite transition times accurate to effectively any
number of significant digits using only the moments with the accuracy increasing
as the index k is increased.
PMID- 29347250
TI - Nonlinear continuous-wave optical propagation in nematic liquid crystals:
Interplay between reorientational and thermal effects.
AB - We investigate nonlinear optical propagation of continuous-wave (CW) beams in
bulk nematic liquid crystals. We thoroughly analyze the competing roles of
reorientational and thermal nonlinearity with reference to self
focusing/defocusing and, eventually, the formation of nonlinear diffraction-free
wavepackets, the so-called spatial optical solitons. To this extent we refer to
dye-doped nematic liquid crystals in planar cells excited by a single CW beam in
the highly nonlocal limit. To adjust the relative weight between the two
nonlinear responses, we employ two distinct wavelengths, inside and outside the
absorption band of the dye, respectively. Different concentrations of the dye are
considered in order to enhance the thermal effect. The theoretical analysis is
complemented by numerical simulations in the highly nonlocal approximation based
on a semi-analytic approach. Theoretical results are finally compared to
experimental results in the Nematic Liquid Crystals (NLC) 4-trans-4'-n
hexylcyclohexylisothiocyanatobenzene (6CHBT) doped with Sudan Blue dye.
PMID- 29347251
TI - Dynamically crowded solutions of infinitely thin Brownian needles.
AB - We study the dynamics of solutions of infinitely thin needles up to densities
deep in the semidilute regime by Brownian dynamics simulations. For high
densities, these solutions become strongly entangled and the motion of a needle
is essentially restricted to a one-dimensional sliding in a confining tube
composed of neighboring needles. From the density-dependent behavior of the
orientational and translational diffusion, we extract the long-time transport
coefficients and the geometry of the confining tube. The sliding motion within
the tube becomes visible in the non-Gaussian parameter of the translational
motion as an extended plateau at intermediate times and in the intermediate
scattering function as an algebraic decay. This transient dynamic arrest is also
corroborated by the local exponent of the mean-square displacements perpendicular
to the needle axis. Moreover, the probability distribution of the displacements
perpendicular to the needle becomes strongly non-Gaussian; rather, it displays an
exponential distribution for large displacements. On the other hand, based on the
analysis of higher-order correlations of the orientation we find that the
rotational motion becomes diffusive again for strong confinement. At coarse
grained time and length scales, the spatiotemporal dynamics of the needle for the
high entanglement is captured by a single freely diffusing phantom needle with
long-time transport coefficients obtained from the needle in solution. The time
dependent dynamics of the phantom needle is also assessed analytically in terms
of spheroidal wave functions. The dynamic behavior of the needle in solution is
found to be identical to needle Lorentz systems, where a tracer needle explores a
quenched disordered array of other needles.
PMID- 29347252
TI - de Almeida-Thouless instability in short-range Ising spin glasses.
AB - We use high-temperature series expansions to study the +/-J Ising spin glass in a
magnetic field in d-dimensional hypercubic lattices for d=5-8 and in the infinite
range Sherrington-Kirkpatrick (SK) model. The expansions are obtained in the
variable w=tanh^{2}J/T for arbitrary values of u=tanh^{2}h/T complete to order
w^{10}. We find that the scaling dimension Delta associated with the ordering
field h^{2} equals 2 in the SK model and for d>=6. However, in agreement with the
work of Fisher and Sompolinsky [Phys. Rev. Lett. 54, 1063 (1985)PRLTAO0031
900710.1103/PhysRevLett.54.1063], there is a violation of scaling in a finite
field, leading to an anomalous h-T dependence of the de Almeida-Thouless (AT) [J.
Phys. A 11, 983 (1978)JPHAC50305-447010.1088/0305-4470/11/5/028] line in high
dimensions, whereas scaling is restored as d->6. Within the convergence of our
series analysis, we present evidence supporting an AT line in d>=6. In d=5, the
exponents gamma and Delta are substantially larger than mean-field values, but we
do not see clear evidence for the AT line in d=5.
PMID- 29347253
TI - Consistent lattice Boltzmann modeling of low-speed isothermal flows at finite
Knudsen numbers in slip-flow regime: Application to plane boundaries.
AB - The first nonequilibrium effect experienced by gaseous flows in contact with
solid surfaces is the slip-flow regime. While the classical hydrodynamic
description holds valid in bulk, at boundaries the fluid-wall interactions must
consider slip. In comparison to the standard no-slip Dirichlet condition, the
case of slip formulates as a Robin-type condition for the fluid tangential
velocity. This makes its numerical modeling a challenging task, particularly in
complex geometries. In this work, this issue is handled with the lattice
Boltzmann method (LBM), motivated by the similarities between the closure
relations of the reflection-type boundary schemes equipping the LBM equation and
the slip velocity condition established by slip-flow theory. Based on this
analogy, we derive, as central result, the structure of the LBM boundary closure
relation that is consistent with the second-order slip velocity condition,
applicable to planar walls. Subsequently, three tasks are performed. First, we
clarify the limitations of existing slip velocity LBM schemes, based on discrete
analogs of kinetic theory fluid-wall interaction models. Second, we present
improved slip velocity LBM boundary schemes, constructed directly at discrete
level, by extending the multireflection framework to the slip-flow regime. Here,
two classes of slip velocity LBM boundary schemes are considered: (i) linear slip
schemes, which are local but retain some calibration requirements and/or
operation limitations, (ii) parabolic slip schemes, which use a two-point
implementation but guarantee the consistent prescription of the intended slip
velocity condition, at arbitrary plane wall discretizations, further dispensing
any numerical calibration procedure. Third and final, we verify the improvements
of our proposed slip velocity LBM boundary schemes against existing ones. The
numerical tests evaluate the ability of the slip schemes to exactly accommodate
the steady Poiseuille channel flow solution, over distinct wall slippage
conditions, namely, no-slip, first-order slip, and second-order slip. The
modeling of channel walls is discussed at both lattice-aligned and non-mesh
aligned configurations: the first case illustrates the numerical slip due to the
incorrect modeling of slippage coefficients, whereas the second case adds the
effect of spurious boundary layers created by the deficient accommodation of bulk
solution. Finally, the slip-flow solutions predicted by LBM schemes are further
evaluated for the Knudsen's paradox problem. As conclusion, this work establishes
the parabolic accuracy of slip velocity schemes as the necessary condition for
the consistent LBM modeling of the slip-flow regime.
PMID- 29347254
TI - Fragmentation approach to the point-island model with hindered aggregation:
Accessing the barrier energy.
AB - We study the effect of hindered aggregation on the island formation process in a
one- (1D) and two-dimensional (2D) point-island model for epitaxial growth with
arbitrary critical nucleus size i. In our model, the attachment of monomers to
preexisting islands is hindered by an additional attachment barrier,
characterized by length l_{a}. For l_{a}=0 the islands behave as perfect sinks
while for l_{a}->infinity they behave as reflecting boundaries. For intermediate
values of l_{a}, the system exhibits a crossover between two different kinds of
processes, diffusion-limited aggregation and attachment-limited aggregation. We
calculate the growth exponents of the density of islands and monomers for the low
coverage and aggregation regimes. The capture-zone (CZ) distributions are also
calculated for different values of i and l_{a}. In order to obtain a good spatial
description of the nucleation process, we propose a fragmentation model, which is
based on an approximate description of nucleation inside of the gaps for 1D and
the CZs for 2D. In both cases, the nucleation is described by using two different
physically rooted probabilities, which are related with the microscopic
parameters of the model (i and l_{a}). We test our analytical model with
extensive numerical simulations and previously established results. The proposed
model describes excellently the statistical behavior of the system for arbitrary
values of l_{a} and i=1, 2, and 3.
PMID- 29347255
TI - From Kardar-Parisi-Zhang scaling to explosive desynchronization in arrays of
limit-cycle oscillators.
AB - Phase oscillator lattices subject to noise are one of the most fundamental
systems in nonequilibrium physics. We have discovered a dynamical transition
which has a significant impact on the synchronization dynamics in such lattices,
as it leads to an explosive increase of the phase diffusion rate by orders of
magnitude. Our analysis is based on the widely applicable Kuramoto-Sakaguchi
model, with local couplings between oscillators. For one-dimensional lattices, we
observe the universal evolution of the phase spread that is suggested by a
connection to the theory of surface growth, as described by the Kardar-Parisi
Zhang (KPZ) model. Moreover, we are able to explain the dynamical transition both
in one and two dimensions by connecting it to an apparent finite-time singularity
in a related KPZ lattice model. Our findings have direct consequences for the
frequency stability of coupled oscillator lattices.
PMID- 29347256
TI - Self-assembly processes of superparamagnetic colloids in a quasi-two-dimensional
system.
AB - Superparamagnetic colloids gather depending on the magnitude of the magnetic
field applied, forming chains and ribbons in a quasi-two-dimensional chamber. The
results presented in this work are in good agreement with recent experimental
multistable data for the mean length of the aggregates in thermodynamic
equilibrium.
PMID- 29347257
TI - Nonuniversality in the erosion of tilted landscapes.
AB - The anisotropic model for landscapes erosion proposed by Pastor-Satorras and
Rothman [R. Pastor-Satorras and D. H. Rothman, Phys. Rev. Lett. 80, 4349
(1998)PRLTAO0031-900710.1103/PhysRevLett.80.4349] is believed to capture the
physics of erosion at intermediate length scale (?3 km), and to account for the
large value of the roughness exponent alpha observed in real data at this scale.
Our study of this model-conducted using the nonperturbative renormalization group
concludes on the nonuniversality of this exponent because of the existence of a
line of fixed points. Thus the roughness exponent depends (weakly) on the details
of the soil and the erosion mechanisms. We conjecture that this feature, while
preserving the generic scaling observed in real data, could explain the wide
spectrum of values of alpha measured for natural landscapes.
PMID- 29347258
TI - Doubly excited pulse waves on thin liquid films flowing down an inclined plane:
An experimental and numerical study.
AB - The interaction patterns between doubly excited pulse waves on thin liquid films
flowing down an inclined plane are studied both experimentally and numerically.
The effect of varying the film flow rate, interpulse interval, and substrate
inclination angle on the pulse interaction patterns is examined. Our results show
that different interaction patterns exist for these binary pulses, which include
solitary wave behavior, partial or complete pulse coalescence, and pulse
noncoalescence. A regime map of these patterns is plotted for each inclination
angle examined, parametrized by the film Reynolds number and interpulse interval.
Finally, the individual effect of the system parameters mentioned above on the
coalescence distance of binary pulses in the "complete pulse coalescence" mode is
studied; the results are compared to numerical simulations of the two-dimensional
Navier-Stokes equations yielding good agreement.
PMID- 29347259
TI - Electro-osmosis of nematic liquid crystals under weak anchoring and second-order
surface effects.
AB - Advent of nematic liquid crystal flows has attracted renewed attention in view of
microfluidic transport phenomena. Among various transport processes, electro
osmosis stands as one of the efficient flow actuation mechanisms through narrow
confinements. In the present study, we explore the electrically actuated flow of
an ordered nematic fluid with ionic inclusions, taking into account the
influences from surface-induced elasticity and electrical double layer (EDL)
phenomena. Toward this, we devise the coupled flow governing equations from
fundamental free-energy analysis, considering the contributions from first- and
second-order elastic, dielectric, flexoelectric, charged surface polarization,
ionic and entropic energies. The present study focuses on the influence of
surface charge and elasticity effects in the resulting linear electro-osmosis
through a slit-type microchannel whose surfaces are chemically treated to display
a homeotropic-type weak anchoring state. An optical periodic stripe configuration
of the nematic director has been observed, especially for higher electric fields,
wherein the Ericksen number for the dynamic study is restricted to the order of
unity. Contrary to the isotropic electrolytes, the EDL potential in this case was
found to be dependent on the external field strength. Through a systematic
investigation, we brought out the fact that the wavelength of the oscillating
patterns is dictated mainly by the external field, while the amplitude depends on
most of the physical variables ranging from the anchoring strength and the
flexoelectric coefficients to the surface charge density and electrical double
layer thickness.
PMID- 29347260
TI - Enhancement of polar anchoring strength in a graphene-nematic suspension and its
effect on nematic electro-optic switching.
AB - A small quantity of monolayer graphene flakes is doped in a nematic liquid
crystal (LC), and the effective polar anchoring strength coefficient between the
LC and the alignment substrate is found to increase by an order of magnitude. The
hexagonal pattern of graphene can interact with the LC's benzene rings via pi-pi
electron stacking, enabling the LC to anchor to the graphene surface
homogeneously (i.e., planar anchoring). When the LC cell is filled with the
graphene-doped LC, some graphene flakes are preferentially attached to the
alignment layer and modify the substrate's anchoring property. These
spontaneously deposited graphene flakes promote planar anchoring at the substrate
and the polar anchoring energy at alignment layer is enhanced significantly. The
enhanced anchoring energy is found to impact favorably on the electro-optic
response of the LC. Additional studies reveal that the nematic electro-optic
switching is significantly faster in the LC-graphene hybrid than that of the pure
LC.
PMID- 29347261
TI - Light propagation in binary kagome ribbons with evolving disorder.
AB - By introducing evolving disorder in the binary kagome ribbons, we study the
establishment of diffusive spreading of flat band states characterized by
diffractionless propagation in regular periodic ribbons. Our numerical analysis
relies on controlling strength and rate of change of disorder during light
propagation while tailoring binarism of the kagome ribbons in order to isolate
the flat band with the gap from the rest of the ribbon's eigenvalue spectrum and
study systematically its influence on diffusion. We show that the flat band plays
a dominant role in the establishment of the diffusion for a given strength and
rate of change of disorder, whereas the rest of the ribbon's eigenvalue spectrum
induces only quantitative differences in the light spreading regimes. Due to the
universality of studied phenomena, our findings may be of interest in various
disordered physical systems with flat spectral bands, ranging from photonics to
ultracold matter systems and plasmonics.
PMID- 29347262
TI - Dynamics of a bilayer membrane coupled to a two-dimensional cytoskeleton: Scale
transfers of membrane deformations.
AB - We theoretically investigate the dynamics of a floating lipid bilayer membrane
coupled with a two-dimensional cytoskeleton network, taking into account
explicitly the intermonolayer friction, the discrete lattice structure of the
cytoskeleton, and its prestress. The lattice structure breaks lateral continuous
translational symmetry and couples Fourier modes with different wave vectors. It
is shown that within a short time interval a long-wavelength deformation excites
a collection of modes with wavelengths shorter than the lattice spacing. These
modes relax slowly with a common renormalized rate originating from the long
wavelength mode. As a result, and because of the prestress, the slowest
relaxation is governed by the intermonolayer friction. Conversely, and most
interestingly, forces applied at the scale of the cytoskeleton for a sufficiently
long time can cooperatively excite large-scale modes.
PMID- 29347263
TI - Modulated phases in a three-dimensional Maier-Saupe model with competing
interactions.
AB - This work is dedicated to the study of the discrete version of the Maier-Saupe
model in the presence of competing interactions. The competition between
interactions favoring different orientational ordering produces a rich phase
diagram including modulated phases. Using a mean-field approach and Monte Carlo
simulations, we show that the proposed model exhibits isotropic and nematic
phases and also a series of modulated phases that meet at a multicritical point,
a Lifshitz point. Though the Monte Carlo and mean-field phase diagrams show some
quantitative disagreements, the Monte Carlo simulations corroborate the general
behavior found within the mean-field approximation.
PMID- 29347264
TI - Statistical mechanics of stochastic growth phenomena.
AB - We develop statistical mechanics for stochastic growth processes and apply it to
Laplacian growth by using its remarkable connection with a random matrix theory.
The Laplacian growth equation is obtained from the variation principle and
describes adiabatic (quasistatic) thermodynamic processes in the two-dimensional
Dyson gas. By using Einstein's theory of thermodynamic fluctuations we consider
transitional probabilities between thermodynamic states, which are in a one-to
one correspondence with simply connected domains occupied by gas. Transitions
between these domains are described by the stochastic Laplacian growth equation,
while the transitional probabilities coincide with a free-particle propagator on
an infinite-dimensional complex manifold with a Kahler metric.
PMID- 29347265
TI - Coarsening with nontrivial in-domain dynamics: Correlations and interface
fluctuations.
AB - Using numerical simulations we investigate the space-time properties of a system
in which spirals emerge within coarsening domains, thus giving rise to nontrivial
internal dynamics. Initially proposed in the context of population dynamics, the
studied six-species model exhibits growing domains composed of three species in a
rock-paper-scissors relationship. Through the investigation of different
quantities, such as space-time correlations and the derived characteristic
length, autocorrelation, density of empty sites, and interface width, we
demonstrate that the nontrivial dynamics inside the domains affects the
coarsening process as well as the properties of the interfaces separating
different domains. Domain growth, aging, and interface fluctuations are shown to
be governed by exponents whose values differ from those expected in systems with
curvature driven coarsening.
PMID- 29347266
TI - Phase separation and folding in swelled nematoelastic films.
AB - We explore reshaping of nematoelastic films upon imbibing an isotropic solvent
under conditions when isotropic and nematic phases coexist. The structure of the
interphase boundary is computed taking into account the optimal nematic
orientation governed by interaction of gradients of the nematic order parameter
and solvent concentration. This structure determines the effective line tension
of the boundary. We further compute equilibrium shapes of deformed thin sheets
and cylindrical and spherical shells with the rectilinear or circular shape of
the boundary between nematic and isotropic domains. A differential expansion or
contraction near this boundary generates a folding pattern spreading out into the
bulk of both phases. The hierarchical ordering of this pattern is most pronounced
on a cylindrical shell.
PMID- 29347267
TI - Decomposition of conditional probability for high-order symbolic Markov chains.
AB - The main goal of this paper is to develop an estimate for the conditional
probability function of random stationary ergodic symbolic sequences with
elements belonging to a finite alphabet. We elaborate on a decomposition
procedure for the conditional probability function of sequences considered to be
high-order Markov chains. We represent the conditional probability function as
the sum of multilinear memory function monomials of different orders (from zero
up to the chain order). This allows us to introduce a family of Markov chain
models and to construct artificial sequences via a method of successive
iterations, taking into account at each step increasingly high correlations among
random elements. At weak correlations, the memory functions are uniquely
expressed in terms of the high-order symbolic correlation functions. The proposed
method fills the gap between two approaches, namely the likelihood estimation and
the additive Markov chains. The obtained results may have applications for
sequential approximation of artificial neural network training.
PMID- 29347268
TI - Nonequilibrium fluctuations during diffusion in liquid layers.
AB - Theoretical analysis and experiments have provided compelling evidence of the
presence of long-range nonequilibrium concentration fluctuations during diffusion
processes in fluids. In this paper, we investigate the dependence of the features
of the fluctuations from the dimensionality of the system. In three-dimensional
fluids the amplitude of nonequilibrium fluctuations can become several orders of
magnitude larger than that of equilibrium fluctuations. Notwithstanding that, the
amplitude of nonequilibrium fluctuations remains small with respect to the
concentration difference driving the diffusion process. By extending the theory
to two-dimensional systems, such as liquid monolayers and bilayers, we show that
the amplitude of the fluctuations becomes much stronger than in three-dimensional
systems. We investigate the properties of the fronts of diffusion and show that
they have a self-affine structure characterized by a Hurst exponent H=1. We
discuss the implications of these results for diffusion in liquid crystals and in
cellular membranes of living organisms.
PMID- 29347269
TI - Length of excitable knots.
AB - In this paper, we present extensive numerical simulations of an excitable medium
to study the long-term dynamics of knotted vortex strings for all torus knots up
to crossing number 11. We demonstrate that FitzHugh-Nagumo evolution preserves
the knot topology for all the examples presented, thereby providing a field
theory approach to the study of knots. Furthermore, the evolution yields a well
defined minimal length for each knot that is comparable to the ropelength of
ideal knots. We highlight the role of the medium boundary in stabilizing the
length of the knot and discuss the implications beyond torus knots. We also show
that there is not a unique attractor within a given knot topology.
PMID- 29347270
TI - Detection of nonstationary transition to synchronized states of a neural network
using recurrence analyses.
AB - We study the stability of asymptotic states displayed by a complex neural
network. We focus on the loss of stability of a stationary state of networks
using recurrence quantifiers as tools to diagnose local and global stabilities as
well as the multistability of a coupled neural network. Numerical simulations of
a neural network composed of 1024 neurons in a small-world connection scheme are
performed using the model of Braun et al. [Int. J. Bifurcation Chaos 08, 881
(1998)IJBEE40218-127410.1142/S0218127498000681], which is a modified model from
the Hodgkin-Huxley model [J. Phys. 117, 500 (1952)]. To validate the analyses,
the results are compared with those produced by Kuramoto's order parameter
[Chemical Oscillations, Waves, and Turbulence (Springer-Verlag, Berlin
Heidelberg, 1984)]. We show that recurrence tools making use of just integrated
signals provided by the networks, such as local field potential (LFP) (LFP
signals) or mean field values bring new results on the understanding of neural
behavior occurring before the synchronization states. In particular we show the
occurrence of different stationary and nonstationarity asymptotic states.
PMID- 29347271
TI - Machine-learning approach for local classification of crystalline structures in
multiphase systems.
AB - Machine learning is one of the most popular fields in computer science and has a
vast number of applications. In this work we will propose a method that will use
a neural network to locally identify crystal structures in a mixed phase Yukawa
system consisting of fcc, hcp, and bcc clusters and disordered particles similar
to plasma crystals. We compare our approach to already used methods and show that
the quality of identification increases significantly. The technique works very
well for highly disturbed lattices and shows a flexible and robust way to
classify crystalline structures that can be used by only providing particle
positions. This leads to insights into highly disturbed crystalline structures.
PMID- 29347272
TI - Nonadiabatic dynamics of the excited states for the Lipkin-Meshkov-Glick model.
AB - We theoretically investigate the impact of the excited state quantum phase
transition on the adiabatic dynamics for the Lipkin-Meshkov-Glick model. Using a
time-dependent protocol, we continuously change a model parameter and then
discuss the scaling properties of the system especially close to the excited
state quantum phase transition where we find that these depend on the energy
eigenstate. On top, we show that the mean-field dynamics with the time-dependent
protocol gives the correct scaling and expectation values in the thermodynamic
limit even for the excited states.
PMID- 29347273
TI - Additive scaling law for structural organization of chromatin in chicken
erythrocyte nuclei.
AB - Small-angle neutron scattering (SANS) on nuclei of chicken erythrocytes
demonstrates the cubic dependence of the scattering intensity Q^{-3} in the range
of momentum transfer Q?10^{-3}-10^{-2}nm^{-1}. Independent spin-echo SANS
measurements give the spin-echo function, which is well described by the
exponential law in a range of sizes (3*10^{2})-(3*10^{4}) nm. Both experimental
dependences reflect the nature of the structural organization of chromatin in the
nucleus of a living cell, which corresponds to the correlation function
gamma(r)=ln(xi/r) for r2. The
onset of this change does not seem to be determined by the extended Harris
criterion.
PMID- 29347312
TI - Experimental investigation of water distribution in a two-phase zone during
gravity-dominated evaporation.
AB - We characterize the water repartition within the partially saturated (two-phase)
zone (PSZ) during evaporation from mixed wettable porous media by controlling the
wettability of glass beads, their sizes, and as well the surrounding relative
humidity. Here, capillary numbers are low and under these conditions, the
percolating front is stabilized by gravity. Using experimental and numerical
analyses, we find that the PSZ saturation decreases with the Bond number, where
packing of smaller particles have higher saturation values than packing made of
larger particles. Results also reveal that the extent (height) of the PSZ, as
well as water saturation in the PSZ, both increase with wettability. We also
numerically calculate the saturation exclusively contained in connected liquid
films and results show that values are less than the expected PSZ saturation.
These results strongly reflect that the two-phase zone is not solely made up of
connected capillary networks but also made of disconnected water clusters or
pockets. Moreover, we also find that global saturation (PSZ + full wet zone)
decreases with wettability, confirming that greater quantity of water is lost via
evaporation with increasing hydrophilicity. These results show that connected
liquid films are favored in more-hydrophilic systems while disconnected water
pockets are favored in less-hydrophilic systems.
PMID- 29347313
TI - Exact mean-energy expansion of Ginibre's gas for coupling constants
Gamma=2*(oddinteger).
AB - Using the approach of a Vandermonde determinant to the power Gamma=Q^{2}/k_{B}T
expansion on monomial functions, a way to find the excess energy U_{exc} of the
two-dimensional one-component plasma (2DOCP) on hard and soft disks (or a Dyson
gas) for odd values of Gamma/2 is provided. At Gamma=2, the present study not
only corroborates the result for the particle-particle energy contribution of the
Dyson gas found by Shakirov [Shakirov, Phys. Lett. A 375, 984
(2011)10.1016/j.physleta.2011.01.004] by using an alternative approach, but also
provides the exact N-finite expansion of the excess energy of the 2DOCP on the
hard disk. The excess energy is fitted to the ansatz of the form
U_{exc}=K^{1}N+K^{2}sqrt[N]+K^{3}+K^{4}/N+O(1/N^{2}) to study the finite-size
correction, with K^{i} coefficients and N the number of particles. In particular,
the bulk term of the excess energy is in agreement with the well known result of
Jancovici for the hard disk in the thermodynamic limit [Jancovici, Phys. Rev.
Lett. 46, 386 (1981)10.1103/PhysRevLett.46.386]. Finally, an expression is found
for the pair correlation function which still keeps a link with the random matrix
theory via the kernel in the Ginibre ensemble [Ginibre, J. Math. Phys. 6, 440
(1965)10.1063/1.1704292] for odd values of Gamma/2. A comparison between the
analytical two-body density function and histograms obtained with Monte Carlo
simulations for small systems and Gamma=2,6,10,... shows that the approach
described in this paper may be used to study analytically the crossover behavior
from systems in the fluid phase to small crystals.
PMID- 29347314
TI - Polymer adsorption on curved surfaces.
AB - The conformational behavior of a coarse-grained finite polymer chain near an
attractive spherical surface was investigated by means of multicanonical Monte
Carlo computer simulations. In a detailed analysis of canonical equilibrium data
over a wide range of sphere radius and temperature, we have constructed entire
phase diagrams both for nongrafted and end-grafted polymers. For the
identification of the conformational phases, we have calculated several energetic
and structural observables such as gyration tensor based shape parameters and
their fluctuations by canonical statistical analysis. Despite the simplicity of
our model, it qualitatively represents in the considered parameter range real
systems that are studied in experiments. The work discussed here could have
experimental implications from protein-ligand interactions to designing nanosmart
materials.
PMID- 29347315
TI - Impact of anticipation in dynamical systems.
AB - Many animals, including humans, have predictive capabilities and, presumably,
base their behavioral decisions-at least partially-upon an anticipated state of
their environment. We explore a minimal version of this idea in the context of
particles that interact according to a pairwise potential. Anticipation enters
the picture by calculating the interparticle forces from linear extrapolations of
the particle positions some time tau in the future. Simulations show that for
intermediate values of tau, compared to a transient time scale defined by the
potential and the initial conditions, the particles form rotating clusters in
which the particles are arranged in a hexagonal pattern. Analysis of the system
shows that anticipation induces energy dissipation and we show that the kinetic
energy asymptotically decays as 1/t. Furthermore, we show that the angular
momentum is not necessarily conserved for tau>0, and that asymmetries in the
initial condition therefore can cause rotational movement. These results suggest
that anticipation could play an important role in collective behavior, since it
may induce pattern formation and stabilizes the dynamics of the system.
PMID- 29347316
TI - Quantum and classical complexity in coupled maps.
AB - We study a generic and paradigmatic two-degrees-of-freedom system consisting of
two coupled perturbed cat maps with different types of dynamics. The Wigner
separability entropy (WSE)-equivalent to the operator space entanglement entropy
and the classical separability entropy (CSE) are used as measures of complexity.
For the case where both degrees of freedom are hyperbolic, the maps are
classically ergodic and the WSE and the CSE behave similarly, growing to higher
values than in the doubly elliptic case. However, when one map is elliptic and
the other hyperbolic, the WSE reaches the same asymptotic value than that of the
doubly hyperbolic case but at a much slower rate. The CSE only follows the WSE
for a few map steps, revealing that classical dynamical features are not enough
to explain complexity growth.
PMID- 29347317
TI - Onset of fractional-order thermal convection in porous media.
AB - The macroscopic description of buoyancy-driven thermal convection in porous media
is governed by advection-diffusion processes, which in the presence of
thermophysical heterogeneities fail to predict the onset of thermal convection
and the average rate of heat transfer. This work extends the classical model of
heat transfer in porous media by including a fractional-order advective
dispersive term to account for the role of thermophysical heterogeneities in
shifting the thermal instability point. The proposed fractional-order model
overcomes limitations of the common closure approaches for the thermal dispersion
term by replacing the diffusive assumption with a fractional-order model. Through
a linear stability analysis and Galerkin procedure, we derive an analytical
formula for the critical Rayleigh number as a function of the fractional model
parameters. The resulting critical Rayleigh number reduces to the classical value
in the absence of thermophysical heterogeneities when solid and fluid phases have
similar thermal conductivities. Numerical simulations of the coupled flow
equation with the fractional-order energy model near the primary bifurcation
point confirm our analytical results. Moreover, data from pore-scale simulations
are used to examine the potential of the proposed fractional-order model in
predicting the amount of heat transfer across the porous enclosure. The linear
stability and numerical results show that, unlike the classical thermal advection
dispersion models, the fractional-order model captures the advance and delay in
the onset of convection in porous media and provides correct scalings for the
average heat transfer in a thermophysically heterogeneous medium.
PMID- 29347318
TI - Entropy production in systems with random transition rates close to equilibrium.
AB - We study the entropy production of systems out of equilibrium using random
networks. We focus on systems with a finite number of states described by a
master equation close to equilibrium. The dynamics are mapped into a network of
states (nodes) connected by transition rates (links). Using this framework, we
analyze the entropy production of ensembles of randomly generated networks owing
to specific constraints (e.g., size or symmetries) and identify the most
important parameters that determine its value. This analysis gives a null-model
estimation for the entropy production that can be used for comparison with
specific systems.
PMID- 29347319
TI - Electromagnetic-radiation absorption by water.
AB - Why does a microwave oven work? How does biological tissue absorb electromagnetic
radiation? Astonishingly, we do not have a definite answer to these simple
questions because the microscopic processes governing the absorption of
electromagnetic waves by water are largely unclarified. This absorption can be
quantified by dielectric loss spectra, which reveal a huge peak at a frequency of
the exciting electric field of about 20 GHz and a gradual tailing off toward
higher frequencies. The microscopic interpretation of such spectra is highly
controversial and various superpositions of relaxation and resonance processes
ascribed to single-molecule or molecule-cluster motions have been proposed for
their analysis. By combining dielectric, microwave, THz, and far-infrared
spectroscopy, here we provide nearly continuous temperature-dependent broadband
spectra of water. Moreover, we find that corresponding spectra for aqueous
solutions reveal the same features as pure water. However, in contrast to the
latter, crystallization in these solutions can be avoided by supercooling. As
different spectral contributions tend to disentangle at low temperatures, this
enables us to deconvolute them when approaching the glass transition under
cooling. We find that the overall spectral development, including the 20 GHz
feature (employed for microwave heating), closely resembles the behavior known
for common supercooled liquids. Thus water's absorption of electromagnetic waves
at room temperature is not unusual but very similar to that of glass-forming
liquids at elevated temperatures, deep in the low-viscosity liquid regime, and
should be interpreted along similar lines.
PMID- 29347320
TI - Neural field model of memory-guided search.
AB - Many organisms can remember locations they have previously visited during a
search. Visual search experiments have shown exploration is guided away from
these locations, reducing redundancies in the search path before finding a hidden
target. We develop and analyze a two-layer neural field model that encodes
positional information during a search task. A position-encoding layer sustains a
bump attractor corresponding to the searching agent's current location, and
search is modeled by velocity input that propagates the bump. A memory layer
sustains persistent activity bounded by a wave front, whose edges expand in
response to excitatory input from the position layer. Search can then be biased
in response to remembered locations, influencing velocity inputs to the position
layer. Asymptotic techniques are used to reduce the dynamics of our model to a
low-dimensional system of equations that track the bump position and front
boundary. Performance is compared for different target-finding tasks.
PMID- 29347321
TI - Analytical solutions for the profile of two-dimensional droplets with finite
length precursor films.
AB - By means of the lubrication approximation we obtain the full family of static
bidimensional profiles of a liquid resting on a substrate under partial-wetting
conditions imposed by a disjoining-conjoining pressure. We show that for a set of
quite general disjoining-conjoining pressure potentials, the free surface can
adopt only five nontrivial static patterns; in particular, we find solutions when
the height goes to zero which describe satisfactorily the complete free surface
for a finite amount of fluid deposited on a substrate. To test the extension of
the applicability of our solutions, we compare them with those obtained when the
lubrication approximations are not employed and under conditions where the
lubrication hypothesis are not strictly valid, and also with axisymmetric
solutions. For a given disjoining-conjoining potential, we report a new
analytical solution that accounts for all the five possible solutions.
PMID- 29347322
TI - Typical equilibrium state of an embedded quantum system.
AB - We consider an arbitrary quantum system coupled nonperturbatively to a large
arbitrary and fully quantum environment. In the work by Ithier and Benaych
Georges [Phys. Rev. A 96, 012108 (2017)2469-992610.1103/PhysRevA.96.012108] the
typicality of the dynamics of such an embedded quantum system was established for
several classes of random interactions. In other words, the time evolution of its
quantum state does not depend on the microscopic details of the interaction.
Focusing on the long-time regime, we use this property to calculate analytically
a partition function characterizing the stationary state and involving the
overlaps between eigenvectors of a bare and a dressed Hamiltonian. This partition
function provides a thermodynamical ensemble which includes the microcanonical
and canonical ensembles as particular cases. We check our predictions with
numerical simulations.
PMID- 29347323
TI - Evolution of inverse cascades and formation of precondensate in Gross-Pitaevskii
turbulence in two dimensions.
AB - Here we study how coherence appears in a system driven by noise at small scales.
In the wave turbulence modeled by the Gross-Pitaevskii or the nonlinear
Schrodinger equation, we observe states with correlation scales smaller than the
system size but much larger than the excitation scale. We call a such state
precondensate to distinguish it from condensate defined as a systemwide coherent
state. Both condensate and precondensate are characterized by large-scale phase
coherence and a narrow distribution of amplitudes. When one excites small scales,
precondensate is achieved relatively quickly by an inverse cascade heating
quasiequilibrium distribution of large-scale modes. The transition from the
precondensate to the systemwide condensate requires a much longer time. The
spectra of precondensate differ from quasiequilibrium and are characterized by
two bending points, one on the scale of the average distance between vortex pairs
and the other on the scale of the distance between vortices in a pair. We suggest
temporal evolution laws for both lengths and use them to predict the probability
of the transition to condensate.
PMID- 29347324
TI - Exponential integrators in time-dependent density-functional calculations.
AB - The integrating factor and exponential time differencing methods are implemented
and tested for solving the time-dependent Kohn-Sham equations. Popular time
propagation methods used in physics, as well as other robust numerical
approaches, are compared to these exponential integrator methods in order to
judge the relative merit of the computational schemes. We determine an
improvement in accuracy of multiple orders of magnitude when describing dynamics
driven primarily by a nonlinear potential. For cases of dynamics driven by a time
dependent external potential, the accuracy of the exponential integrator methods
are less enhanced but still match or outperform the best of the conventional
methods tested.
PMID- 29347325
TI - Two-step relaxation mode analysis with multiple evolution times applied to all
atom molecular dynamics protein simulation.
AB - Proteins implement their functionalities when folded into specific three
dimensional structures, and their functions are related to the protein structures
and dynamics. Previously, we applied a relaxation mode analysis (RMA) method to
protein systems; this method approximately estimates the slow relaxation modes
and times via simulation and enables investigation of the dynamic properties
underlying the protein structural fluctuations. Recently, two-step RMA with
multiple evolution times has been proposed and applied to a slightly complex
homopolymer system, i.e., a single [n]polycatenane. This method can be applied to
more complex heteropolymer systems, i.e., protein systems, to estimate the
relaxation modes and times more accurately. In two-step RMA, we first perform RMA
and obtain rough estimates of the relaxation modes and times. Then, we apply RMA
with multiple evolution times to a small number of the slowest relaxation modes
obtained in the previous calculation. Herein, we apply this method to the results
of principal component analysis (PCA). First, PCA is applied to a 2-MUs molecular
dynamics simulation of hen egg-white lysozyme in aqueous solution. Then, the two
step RMA method with multiple evolution times is applied to the obtained
principal components. The slow relaxation modes and corresponding relaxation
times for the principal components are much improved by the second RMA.
PMID- 29347326
TI - Equation of state of polydisperse hard-disk mixtures in the high-density regime.
AB - A proposal to link the equation of state of a monocomponent hard-disk fluid to
the equation of state of a polydisperse hard-disk mixture is presented. Event
driven molecular dynamics simulations are performed to obtain data for the
compressibility factor of the monocomponent fluid and of 26 polydisperse mixtures
with different size distributions. Those data are used to assess the proposal and
to infer the values of the compressibility factor of the monocomponent hard-disk
fluid in the metastable region from those of mixtures in the high-density region.
The collapse of the curves for the different mixtures is excellent in the stable
region. In the metastable regime, except for two mixtures in which
crystallization is present, the outcome of the approach exhibits a rather good
performance. The simulation results indicate that a (reduced) variance of the
size distribution larger than about 0.01 is sufficient to avoid crystallization
and explore the metastable fluid branch.
PMID- 29347327
TI - Effective dielectric response of dispersions of graded particles.
AB - Based upon our compact group approach and the Hashin-Shtrikman variational
theorem, we propose a solution, which effectively incorporates many-particle
effects in concentrated systems, to the problem of the effective quasistatic
permittivity of dispersions of graded dielectric particles. After the theory is
shown to recover existing analytical results and simulation data for dispersions
of hard dielectric spheres with power-law permittivity profiles, we use it to
describe the effective dielectric response of nonconducting polymer-ceramic
composites modeled as dispersions of dielectric core-shell particles. Possible
generalizations of the results are specified.
PMID- 29347328
TI - Chaos and unpredictability in evolution of cooperation in continuous time.
AB - Cooperators benefit others with paying costs. Evolution of cooperation crucially
depends on the cost-benefit ratio of cooperation, denoted as c. In this work, we
investigate the infinitely repeated prisoner's dilemma for various values of c
with four of the representative memory-one strategies, i.e., unconditional
cooperation, unconditional defection, tit-for-tat, and win-stay-lose-shift. We
consider replicator dynamics which deterministically describes how the fraction
of each strategy evolves over time in an infinite-sized well-mixed population in
the presence of implementation error and mutation among the four strategies. Our
finding is that this three-dimensional continuous-time dynamics exhibits chaos
through a bifurcation sequence similar to that of a logistic map as c varies. If
mutation occurs with rate MU?1, the position of the bifurcation sequence on the c
axis is numerically found to scale as MU^{0.1}, and such sensitivity to MU
suggests that mutation may have nonperturbative effects on evolutionary paths. It
demonstrates how the microscopic randomness of the mutation process can be
amplified to macroscopic unpredictability by evolutionary dynamics.
PMID- 29347329
TI - Unified implicit kinetic scheme for steady multiscale heat transfer based on the
phonon Boltzmann transport equation.
AB - An implicit kinetic scheme is proposed to solve the stationary phonon Boltzmann
transport equation (BTE) for multiscale heat transfer problem. Compared to the
conventional discrete ordinate method, the present method employs a macroscopic
equation to accelerate the convergence in the diffusive regime. The macroscopic
equation can be taken as a moment equation for phonon BTE. The heat flux in the
macroscopic equation is evaluated from the nonequilibrium distribution function
in the BTE, while the equilibrium state in BTE is determined by the macroscopic
equation. These two processes exchange information from different scales, such
that the method is applicable to the problems with a wide range of Knudsen
numbers. Implicit discretization is implemented to solve both the macroscopic
equation and the BTE. In addition, a memory reduction technique, which is
originally developed for the stationary kinetic equation, is also extended to
phonon BTE. Numerical comparisons show that the present scheme can predict
reasonable results both in ballistic and diffusive regimes with high efficiency,
while the memory requirement is on the same order as solving the Fourier law of
heat conduction. The excellent agreement with benchmark and the rapid converging
history prove that the proposed macro-micro coupling is a feasible solution to
multiscale heat transfer problems.
PMID- 29347330
TI - Lagrangian formulation and symmetrical description of liquid dynamics.
AB - Theoretical description of liquids has been primarily based on the hydrodynamic
approach and its generalization to the solid-like regime. We show that the same
liquid properties can be derived starting from solid-like equations and
generalizing them to account for the hydrodynamic flow. Both approaches predict
propagating shear waves with the notable gap in k-space. This gives an important
symmetry of liquids regarding their description. We subsequently construct a two
field Lagrangian of liquid dynamics where the dissipative hydrodynamic and solid
like terms are treated on equal footing. The Lagrangian predicts two gapped waves
propagating in opposite space-time directions. The dissipative and mass terms
compete by promoting gaps in k-space and energy, respectively. When bare mass is
close to the field hopping frequency, both gaps close and the dissipative term
annihilates the bare mass.
PMID- 29347331
TI - Two-dimensional collective electron magnetotransport, oscillations, and chaos in
a semiconductor superlattice.
AB - When quantized, traces of classically chaotic single-particle systems include
eigenvalue statistics and scars in eigenfuntions. Since 2001, many theoretical
and experimental works have argued that classically chaotic single-electron
dynamics influences and controls collective electron transport. For transport in
semiconductor superlattices under tilted magnetic and electric fields, these
theories rely on a reduction to a one-dimensional self-consistent drift model. A
two-dimensional theory based on self-consistent Boltzmann transport does not
support that single-electron chaos influences collective transport. This theory
agrees with existing experimental evidence of current self-oscillations, predicts
spontaneous collective chaos via a period doubling scenario, and could be tested
unambiguously by measuring the electric potential inside the superlattice under a
tilted magnetic field.
PMID- 29347332
TI - Linear and nonlinear market correlations: Characterizing financial crises and
portfolio optimization.
AB - Pearson correlation and mutual information-based complex networks of the day-to
day returns of U.S. S&P500 stocks between 1985 and 2015 have been constructed to
investigate the mutual dependencies of the stocks and their nature. We show that
both networks detect qualitative differences especially during (recent) turbulent
market periods, thus indicating strongly fluctuating interconnections between the
stocks of different companies in changing economic environments. A measure for
the strength of nonlinear dependencies is derived using surrogate data and leads
to interesting observations during periods of financial market crises. In
contrast to the expectation that dependencies reduce mainly to linear
correlations during crises, we show that (at least in the 2008 crisis) nonlinear
effects are significantly increasing. It turns out that the concept of centrality
within a network could potentially be used as some kind of an early warning
indicator for abnormal market behavior as we demonstrate with the example of the
2008 subprime mortgage crisis. Finally, we apply a Markowitz mean variance
portfolio optimization and integrate the measure of nonlinear dependencies to
scale the investment exposure. This leads to significant outperformance as
compared to a fully invested portfolio.
PMID- 29347333
TI - Extending electrostatics of dielectric spheres to arbitrary charge distributions
with applications to biosystems.
AB - A previously developed classical model of electrostatic interactions, based on a
formalism of dielectric spheres, which has been found to have surprising accuracy
for S state atoms, is extended by allowing higher-order moments of the intrinsic
charge distribution. Two methods to introduce the charge distribution (point
moments at the center vs surface charge) are shown to be equivalent and are
compared with another common model for polarizable atoms that utilizes
polarizable point dipoles. Unlike the polarizable point dipole model, the
polarizable spheres models do not suffer from a divergence at small separation of
atoms and are easily generalized to higher multipoles.
PMID- 29347334
TI - Sequence selection by dynamical symmetry breaking in an autocatalytic binary
polymer model.
AB - Template-directed replication of nucleic acids is at the essence of all living
beings and a major milestone for any origin of life scenario. We present an
idealized model of prebiotic sequence replication, where binary polymers act as
templates for their autocatalytic replication, thereby serving as each others
reactants and products in an intertwined molecular ecology. Our model
demonstrates how autocatalysis alters the qualitative and quantitative system
dynamics in counterintuitive ways. Most notably, numerical simulations reveal a
very strong intrinsic selection mechanism that favors the appearance of a few
population structures with highly ordered and repetitive sequence patterns when
starting from a pool of monomers. We demonstrate both analytically and through
simulation how this "selection of the dullest" is caused by continued symmetry
breaking through random fluctuations in the transient dynamics that are amplified
by autocatalysis and eventually propagate to the population level. The impact of
these observations on related prebiotic mathematical models is discussed.
PMID- 29347335
TI - Saturation of entropy production in quantum many-body systems.
AB - Bridging the second law of thermodynamics and microscopic reversible dynamics has
been a longstanding problem in statistical physics. Here, we address this problem
on the basis of quantum many-body physics, and discuss how the entropy production
saturates in isolated quantum systems under unitary dynamics. First, we
rigorously prove that the entropy production does indeed saturate in the long
time regime, even when the total system is in a pure state. Second, we discuss
the non-negativity of the entropy production at saturation, implying the second
law of thermodynamics. This is based on the eigenstate thermalization hypothesis,
which states that even a single energy eigenstate is thermal. We also numerically
demonstrate that the entropy production saturates at a non-negative value even
when the initial state of a heat bath is a single energy eigenstate. Our results
reveal fundamental properties of the entropy production in isolated quantum
systems at late times.
PMID- 29347336
TI - Numerical study of two disks settling in an Oldroyd-B fluid: From periodic
interaction to chaining.
AB - In this article, we present a numerical study of the dynamics of two disks
sedimenting in a narrow vertical channel filled with an Oldroyd-B fluid. Two
kinds of particle dynamics are observed: (i) a periodic interaction between the
two disks, and (ii) the formation of a two-disk chain. For the periodic
interaction of the two disks, two different motions are observed: (a) the two
disks stay far apart and interact periodically, and (b) the two disks interact
closely and then far apart in a periodic way, like the drafting, kissing, and
tumbling of two disks sedimenting in a Newtonian fluid, due to a weak elastic
force. Concerning the formation of a two-disk chain occurring at higher values of
the elasticity number, either a tilted chain or a vertical chain is observed. Our
simulations show that, as expected, the values of the elasticity and Mach numbers
are the determining factors concerning the particle chain formation and its
orientation.
PMID- 29347337
TI - Controlling percolation with limited resources.
AB - Connectivity, or the lack thereof, is crucial for the function of many man-made
systems, from financial and economic networks over epidemic spreading in social
networks to technical infrastructure. Often, connections are deliberately
established or removed to induce, maintain, or destroy global connectivity. Thus,
there has been a great interest in understanding how to control percolation, the
transition to large-scale connectivity. Previous work, however, studied control
strategies assuming unlimited resources. Here, we depart from this unrealistic
assumption and consider the effect of limited resources on the effectiveness of
control. We show that, even for scarce resources, percolation can be controlled
with an efficient intervention strategy. We derive such an efficient strategy and
study its implications, revealing a discontinuous transition as an unintended
side effect of optimal control.
PMID- 29347338
TI - Numerical solution of modified differential equations based on symmetry
preservation.
AB - In this paper, we propose a method to construct invariant finite-difference
schemes for solution of partial differential equations (PDEs) via consideration
of modified forms of the underlying PDEs. The invariant schemes, which preserve
Lie symmetries, are obtained based on the method of equivariant moving frames.
While it is often difficult to construct invariant numerical schemes for PDEs due
to complicated symmetry groups associated with cumbersome discrete variable
transformations, we note that symmetries associated with more convenient
transformations can often be obtained by appropriately modifying the original
PDEs. In some cases, modifications to the original PDEs are also found to be
useful in order to avoid trivial solutions that might arise from particular
selections of moving frames. In our proposed method, modified forms of PDEs can
be obtained either by addition of perturbation terms to the original PDEs or
through defect correction procedures. These additional terms, whose primary
purpose is to enable symmetries with more convenient transformations, are then
removed from the system by considering moving frames for which these specific
terms go to zero. Further, we explore selection of appropriate moving frames that
result in improvement in accuracy of invariant numerical schemes based on
modified PDEs. The proposed method is tested using the linear advection equation
(in one- and two-dimensions) and the inviscid Burgers' equation. Results obtained
for these tests cases indicate that numerical schemes derived from the proposed
method perform significantly better than existing schemes not only by virtue of
improvement in numerical accuracy but also due to preservation of qualitative
properties or symmetries of the underlying differential equations.
PMID- 29347339
TI - Rheology of dense granular flows for elongated particles.
AB - We study the rheology of dense granular flows for frictionless spherocylinders by
means of 3D numerical simulations. As in the case of spherical particles, the
effective friction MU is an increasing function of the inertial number I, and we
systematically investigate the dependence of MU on the particle aspect ratio Q,
as well as that of the normal stress differences, the volume fraction, and the
coordination number. We show in particular that the quasistatic friction
coefficient is nonmonotonic with Q: from the spherical case Q=1, it first sharply
increases, reaches a maximum around Q?1.05, and then gently decreases until Q=3,
passing its initial value at Q?2. We provide a microscopic interpretation for
this unexpected behavior through the analysis of the distribution of dissipative
contacts around the particles: as compared to spheres, slightly elongated grains
enhance contacts in their central cylindrical band, whereas at larger aspect
ratios particles tend to align and dissipate by preferential contacts at their
hemispherical caps.
PMID- 29347340
TI - Mirror node correlations tuning synchronization in multiplex networks.
AB - We show that the degree-degree correlations have a major impact on global
synchronizability (GS) of multiplex networks, enabling the specification of
synchronizability by only changing the degree-degree correlations of the mirror
nodes while maintaining the connection architecture of the individual layer
unaltered. If individual layers have nodes that are mildly correlated, the
multiplex network is best synchronizable when the mirror degrees are strongly
negatively correlated. If individual layers have nodes with strong degree-degree
correlations, mild correlations among the degrees of mirror nodes are the best
strategy for the optimization of GS. Global synchronization also depend on the
density of connections, a phenomenon not observed in a single layer network. The
results are crucial to understand, predict, and specify behavior of systems
having multiple types of connections among the interacting units.
PMID- 29347341
TI - Spatial correlations of hydrodynamic fluctuations in simple fluids under shear
flow: A mesoscale simulation study.
AB - Hydrodynamic fluctuations in simple fluids under shear flow are demonstrated to
be spatially correlated, in contrast to the fluctuations at equilibrium, using
mesoscopic hydrodynamic simulations. The simulation results for the equal-time
hydrodynamic correlations in a multiparticle collision dynamics (MPC) fluid in
shear flow are compared with the explicit expressions obtained from fluctuating
hydrodynamics calculations. For large wave vectors k, the nonequilibrium
contributions to transverse and longitudinal velocity correlations decay as k^{
4} for wave vectors along the flow direction and as k^{-2} for the off-flow
directions. For small wave vectors, a crossover to a slower decay occurs,
indicating long-range correlations in real space. The coupling between the
transverse velocity components, which vanishes at equilibrium, also exhibits a
k^{-2} dependence on the wave vector. In addition, we observe a quadratic
dependency on the shear rate of the nonequilibrium contribution to pressure.
PMID- 29347342
TI - Synchronization of coupled active rotators by common noise.
AB - We study the effect of common noise on coupled active rotators. While such a
noise always facilitates synchrony, coupling may be attractive (synchronizing) or
repulsive (desynchronizing). We develop an analytical approach based on a
transformation to approximate angle-action variables and averaging over fast
rotations. For identical rotators, we describe a transition from full to partial
synchrony at a critical value of repulsive coupling. For nonidentical rotators,
the most nontrivial effect occurs at moderate repulsive coupling, where a
juxtaposition of phase locking with frequency repulsion (anti-entrainment) is
observed. We show that the frequency repulsion obeys a nontrivial power law.
PMID- 29347343
TI - Dissipation, lag, and drift in driven fluctuating systems.
AB - This work deals with thermostated fluctuating systems subjected to driven
transformations of the internal energetics. The main focus is on generally
multidimensional systems with continuous configurational degrees of freedom over
which overdamped Markovian fluctuations take place (diffusive regime of the
motion). Mutual bounds are established between the average energy dissipation,
the deviation between nonequilibrium probability density and underlying
equilibrium distribution due to the system's lag, and the statistical properties
of the components of the directed flow induced by the transformation itself. The
directed flow is here expressed in terms of time-dependent "drift velocity"
associated with the probability current in a advection-like formulation of the
nonstationary Fokker-Planck equation. Consideration of the drift makes that the
bounds achieved here extend the inequality derived by Vaikuntanathan and
Jarzynski [Europhys. Lett. 87, 60005 (2009)EULEEJ0295-507510.1209/0295
5075/87/60005] involving only dissipation and lag. The key relations are then
specified for the so-called stochastic pumps, i.e., systems that reach a periodic
steady state in response of cyclic transformations and that are prototypes of
nonautonomous dissipative converters of input energy into directed motion; a one
dimensional case model is adopted to illustrate the main features. Complementary
results concerning bounds between the evolution rates of dissipation and lag,
valid for both overdamped and underdamped dynamics, are also presented.
PMID- 29347344
TI - Experimental investigation of mesoscopic heterogeneous motion of laser-activated
self-propelling Janus particles in suspension.
AB - The mesoscopic collective motion of self-propelling active particle suspension is
experimentally investigated. The active particles are silica micro spheres with
Au hemisphere coating, and their propelling strength is activated by laser
irradiation. The suspension is driven from equilibrium to near equilibrium and
far from equilibrium by tuning the excitation laser intensity. By use of the long
term particle tracking technique, the time evolution of a large amount of active
particles is resolvable. For low laser intensity, the suspension is driven to
near equilibrium state with homogeneous superdiffusion motion. The strength of
enhanced superdiffusion is monotonically related to the laser intensity. For high
laser intensity, the motility-induced phase separation with the coexistence of
dense cluster and very dilute individual particle are observed. It leads to
highly heterogeneous dynamic with less mobile jammed cluster and fast-moving
particles and subsequently suppresses the enhanced superdiffusion. Such
heterogeneous dynamics is similar to many far from equilibrium systems. Finally,
the degree away from equilibrium (Gaussian dynamics) triggered by propelling
strength is quantified by non-Gaussian parameters.
PMID- 29347345
TI - Effect of temperature on the dynamics and geometry of reactive-wetting interfaces
around room temperature.
AB - The temperature effect on the dynamics and geometry of a mercury droplet (~150
MUm) spreading on a silver substrate (4000 A) was studied. The system temperature
was controlled by a heating stage in the temperature range of -15 degrees C < T
< 25 degrees C, and the spreading process was monitored using an optical
microscope. We studied the wetting dynamics (droplet radius and velocity) as a
function of temperature. We found that for all studied temperatures, the
spreading radius R(t) grows linearly with time, with a velocity value depending
on temperature. We also studied the temperature effect on the kinetic roughening
properties of the advancing interface (growth (beta) and roughness (alpha)
exponents). Our results show that the growth exponent increases with temperature
while the roughness exponent is relatively constant. In addition, we obtained the
system's activation energy at this temperature range.
PMID- 29347346
TI - Elucidating distinct ion channel populations on the surface of hippocampal
neurons via single-particle tracking recurrence analysis.
AB - Protein and lipid nanodomains are prevalent on the surface of mammalian cells. In
particular, it has been recently recognized that ion channels assemble into
surface nanoclusters in the soma of cultured neurons. However, the interactions
of these molecules with surface nanodomains display a considerable degree of
heterogeneity. Here, we investigate this heterogeneity and develop statistical
tools based on the recurrence of individual trajectories to identify
subpopulations within ion channels in the neuronal surface. We specifically study
the dynamics of the K^{+} channel Kv1.4 and the Na^{+} channel Nav1.6 on the
surface of cultured hippocampal neurons at the single-molecule level. We find
that both these molecules are expressed in two different forms with distinct
kinetics with regards to surface interactions, emphasizing the complex proteomic
landscape of the neuronal surface. Further, the tools presented in this work
provide new methods for the analysis of membrane nanodomains, transient
confinement, and identification of populations within single-particle
trajectories.
PMID- 29347347
TI - Energetics in a model of prebiotic evolution.
AB - Previously we reported [A. Wynveen et al., Phys. Rev. E 89, 022725
(2014)PLEEE81539-375510.1103/PhysRevE.89.022725] that requiring that the systems
regarded as lifelike be out of chemical equilibrium in a model of abstracted
polymers undergoing ligation and scission first introduced by Kauffman [S. A.
Kauffman, The Origins of Order (Oxford University Press, New York, 1993), Chap.
7] implied that lifelike systems were most probable when the reaction network was
sparse. The model was entirely statistical and took no account of the bond
energies or other energetic constraints. Here we report results of an extension
of the model to include effects of a finite bonding energy in the model. We
studied two conditions: (1) A food set is continuously replenished and the total
polymer population is constrained but the system is otherwise isolated and (2) in
addition to the constraints in (1) the system is in contact with a finite
temperature heat bath. In each case, detailed balance in the dynamics is
guaranteed during the computations by continuous recomputation of a temperature
[in case (1)] and of the chemical potential (in both cases) toward which the
system is driven by the dynamics. In the isolated case, the probability of
reaching a metastable nonequilibrium state in this model depends significantly on
the composition of the food set, and the nonequilibrium states satisfying
lifelike condition turn out to be at energies and particle numbers consistent
with an equilibrium state at high negative temperature. As a function of the
sparseness of the reaction network, the lifelike probability is nonmonotonic, as
in our previous model, but the maximum probability occurs when the network is
less sparse. In the case of contact with a thermal bath at a positive ambient
temperature, we identify two types of metastable nonequilibrium states, termed
locally and thermally alive, and locally dead and thermally alive, and evaluate
their likelihood of appearance, finding maxima at an optimal temperature and an
optimal degree of sparseness in the network. We use a Euclidean metric in the
space of polymer populations to distinguish these states from one another and
from fully equilibrated states. The metric can be used to characterize the degree
and type of chemical equilibrium in observed systems, as we illustrate for the
proteome of the ribosome.
PMID- 29347348
TI - Consciousness as a global property of brain dynamic activity.
AB - We seek general principles of the structure of the cellular collective activity
associated with conscious awareness. Can we obtain evidence for features of the
optimal brain organization that allows for adequate processing of stimuli and
that may guide the emergence of cognition and consciousness? Analyzing brain
recordings in conscious and unconscious states, we followed initially the classic
approach in physics when it comes to understanding collective behaviours of
systems composed of a myriad of units: the assessment of the number of possible
configurations (microstates) that the system can adopt, for which we use a global
entropic measure associated with the number of connected brain regions. Having
found maximal entropy in conscious states, we then inspected the microscopic
nature of the configurations of connections using an adequate complexity measure
and found higher complexity in states characterized not only by conscious
awareness but also by subconscious cognitive processing, such as sleep stages.
Our observations indicate that conscious awareness is associated with maximal
global (macroscopic) entropy and with the short time scale (microscopic)
complexity of the configurations of connected brain networks in pathological
unconscious states (seizures and coma), but the microscopic view captures the
high complexity in physiological unconscious states (sleep) where there is
information processing. As such, our results support the global nature of
conscious awareness, as advocated by several theories of cognition. We thus hope
that our studies represent preliminary steps to reveal aspects of the structure
of cognition that leads to conscious awareness.
PMID- 29347349
TI - Importance sampling with imperfect cloning for the computation of generalized
Lyapunov exponents.
AB - We revisit the numerical calculation of generalized Lyapunov exponents, L(q), in
deterministic dynamical systems. The standard method consists of adding noise to
the dynamics in order to use importance sampling algorithms. Then L(q) is
obtained by taking the limit noise-amplitude -> 0 after the calculation. We focus
on a particular method that involves periodic cloning and pruning of a set of
trajectories. However, instead of considering a noisy dynamics, we implement an
imperfect (noisy) cloning. This alternative method is compared with the standard
one and, when possible, with analytical results. As a workbench we use the
asymmetric tent map, the standard map, and a system of coupled symplectic maps.
The general conclusion of this study is that the imperfect-cloning method
performs as well as the standard one, with the advantage of preserving the
deterministic dynamics.
PMID- 29347350
TI - Birth of a subaqueous barchan dune.
AB - Barchan dunes are crescentic shape dunes with horns pointing downstream. The
present paper reports the formation of subaqueous barchan dunes from initially
conical heaps in a rectangular channel. Because the most unique feature of a
barchan dune is its horns, we associate the time scale for the appearance of
horns to the formation of a barchan dune. A granular heap initially conical was
placed on the bottom wall of a closed conduit and it was entrained by a water
flow in turbulent regime. After a certain time, horns appear and grow, until an
equilibrium length is reached. Our results show the existence of the time scales
0.5t_{c} and 2.5t_{c} for the appearance and equilibrium of horns, respectively,
where t_{c} is a characteristic time that scales with the grains diameter,
gravity acceleration, densities of the fluid and grains, and shear and threshold
velocities.
PMID- 29347351
TI - Kinetics of doublet formation in bicomponent magnetic suspensions: The role of
the magnetic permeability anisotropy.
AB - Micron-sized particles (microbeads) dispersed in a suspension of magnetic
nanoparticles, i.e., ferrofluids, can be assembled into different types of
structures upon application of an external magnetic field. This paper is devoted
to theoretical modeling of a relative motion of a pair of microbeads (either soft
ferromagnetic or diamagnetic) in the ferrofluid under the action of applied
uniform magnetic field which induces magnetic moments in the microbeads making
them attracting to each other. The model is based on a point-dipole approximation
for the magnetic interactions between microbeads mediated by the ferrofluid;
however, the ferrofluid is considered to possess an anisotropic magnetic
permeability thanks to field-induced structuring of its nanoparticles. The model
is tested against experimental results and shows generally better agreement with
experiments than the model considering isotropic magnetic permeability of
ferrofluids. The results could be useful for understanding kinetics of
aggregation of microbeads suspended in a ferrofluid. From a broader perspective,
the present study is believed to contribute to a general understanding of
particle behaviors in anisotropic media.
PMID- 29347352
TI - Simple scaling laws for the evaporation of droplets pinned on pillars: Transfer
rate- and diffusion-limited regimes.
AB - The evaporation of droplets can give rise to a wide range of interesting
phenomena in which the dynamics of the evaporation are crucial. In this work, we
find simple scaling laws for the evaporation dynamics of axisymmetric droplets
pinned on millimeter-sized pillars. Different laws are found depending on whether
evaporation is limited by the diffusion of vapor molecules or by the transfer
rate across the liquid-vapor interface. For the diffusion-limited regime, we find
that a mass-loss rate equal to 3/7 of that of a free-standing evaporating droplet
brings a good balance between simplicity and physical correctness. We also find a
scaling law for the evaporation of multicomponent solutions. The scaling laws
found are validated against experiments of the evaporation of droplets of (1)
water, (2) blood plasma, and (3) a mixture of water and polyethylene glycol,
pinned on acrylic pillars of different diameters. These results shed light on the
macroscopic dynamics of evaporation on pillars as a first step towards the
understanding of other complex phenomena that may be taking place during the
evaporation process, such as particle transport and chemical reactions.
PMID- 29347353
TI - Theory of nonstationary Hawkes processes.
AB - We expand the theory of Hawkes processes to the nonstationary case, in which the
mutually exciting point processes receive time-dependent inputs. We derive an
analytical expression for the time-dependent correlations, which can be applied
to networks with arbitrary connectivity, and inputs with arbitrary statistics.
The expression shows how the network correlations are determined by the interplay
between the network topology, the transfer functions relating units within the
network, and the pattern and statistics of the external inputs. We illustrate the
correlation structure using several examples in which neural network dynamics are
modeled as a Hawkes process. In particular, we focus on the interplay between
internally and externally generated oscillations and their signatures in the
spike and rate correlation functions.
PMID- 29347354
TI - Coarsening and pattern formation during true morphological phase separation in
unstable thin films under gravity.
AB - We address in detail the problem of true morphological phase separation (MPS) in
three-dimensional or (2+1)-dimensional unstable thin liquid films (>100nm) under
the influence of gravity. The free-energy functionals of these films are
asymmetric and show two points of common tangency, which facilitates the
formation of two equilibrium phases. Three distinct patterns formed by relative
preponderance of these phases are clearly identified in "true MPS". Asymmetricity
induces two different pathways of pattern formation, viz., defect and direct
pathway for true MPS. The pattern formation and phase-ordering dynamics have been
studied using statistical measures such as structure factor, correlation
function, and growth laws. In the late stage of coarsening, the system reaches
into a scaling regime for both pathways, and the characteristic domain size
follows the Lifshitz-Slyozov growth law [L(t)~t^{1/3}]. However, for the defect
pathway, there is a crossover of domain growth behavior from L(t)~t^{1/4}
>t^{1/3} in the dynamical scaling regime. We also underline the analogies and
differences behind the mechanisms of MPS and true MPS in thin liquid films and
generic spinodal phase separation in binary mixtures.
PMID- 29347355
TI - Inverse Ising problem in continuous time: A latent variable approach.
AB - We consider the inverse Ising problem: the inference of network couplings from
observed spin trajectories for a model with continuous time Glauber dynamics. By
introducing two sets of auxiliary latent random variables we render the
likelihood into a form which allows for simple iterative inference algorithms
with analytical updates. The variables are (1) Poisson variables to linearize an
exponential term which is typical for point process likelihoods and (2) Polya
Gamma variables, which make the likelihood quadratic in the coupling parameters.
Using the augmented likelihood, we derive an expectation-maximization (EM)
algorithm to obtain the maximum likelihood estimate of network parameters. Using
a third set of latent variables we extend the EM algorithm to sparse couplings
via L1 regularization. Finally, we develop an efficient approximate Bayesian
inference algorithm using a variational approach. We demonstrate the performance
of our algorithms on data simulated from an Ising model. For data which are
simulated from a more biologically plausible network with spiking neurons, we
show that the Ising model captures well the low order statistics of the data and
how the Ising couplings are related to the underlying synaptic structure of the
simulated network.
PMID- 29347356
TI - First- and second-order quantum phase transitions of a q-state Potts model in
fractal lattices.
AB - Quantum phase transitions of a q-state Potts model in fractal lattices are
studied using a continuous-time quantum Monte Carlo simulation technique. For
small values of q, the transition is found to be second order and critical
exponents of the quantum critical point are calculated. The dynamic critical
exponent z is found to be greater than one for all fractals studied, which is in
contrast to integer-dimensional regular lattices. When q is greater than a
certain value q_{c}, the phase transition becomes first order, where q_{c}
depends on the lattice. Further analysis shows that the characteristics of phase
transitions are more sensitive to the average number of nearest neighbors than
the Hausdorff dimension or the order of ramification.
PMID- 29347357
TI - Coupled Lorenz oscillators near the Hopf boundary: Multistability, intermingled
basins, and quasiriddling.
AB - We investigate the dynamics of coupled identical chaotic Lorenz oscillators just
above the subcritical Hopf bifurcation. In the absence of coupling, the motion is
on a strange chaotic attractor and the fixed points of the system are all
unstable. With the coupling, the unstable fixed points are converted into chaotic
attractors, and the system can exhibit a multiplicity of coexisting attractors.
Depending on the strength of the coupling, the motion of the individual
oscillators can be synchronized (both in and out of phase) or desynchronized and
in addition there can be mixed phases. We find that the basins have a complex
structure: the state that is asymptotically reached shows extreme sensitivity to
initial conditions. The basins of attraction of these different states are
characterized using a variety of measures and depending on the strength of the
coupling, they are intermingled or quasiriddled.
PMID- 29347358
TI - Divergence of activity expansions: Is it actually a problem?
AB - For realistic interaction models, which include both molecular attraction and
repulsion (e.g., Lennard-Jones, modified Lennard-Jones, Morse, and square-well
potentials), the asymptotic behavior of the virial expansions for pressure and
density in powers of activity has been studied taking power terms of high orders
into account on the basis of the known finite-order irreducible integrals as well
as the recent approximations of infinite irreducible series. Even in the
divergence region (at subcritical temperatures), this behavior stays
thermodynamically adequate (in contrast to the behavior of the virial equation of
state with the same set of irreducible integrals) and corresponds to the
beginning of the first-order phase transition: the divergence yields the jump
(discontinuity) in density at constant pressure and chemical potential. In
general, it provides a statistical explanation of the condensation phenomenon,
but for liquid or solid states, the physically proper description (which can turn
the infinite discontinuity into a finite jump of density) still needs further
study of high-order cluster integrals and, especially, their real dependence on
the system volume (density).
PMID- 29347359
TI - Self-organized emergence of multilayer structure and chimera states in dynamical
networks with adaptive couplings.
AB - We report the phenomenon of self-organized emergence of hierarchical multilayered
structures and chimera states in dynamical networks with adaptive couplings. This
process is characterized by a sequential formation of subnetworks (layers) of
densely coupled elements, the size of which is ordered in a hierarchical way, and
which are weakly coupled between each other. We show that the hierarchical
structure causes the decoupling of the subnetworks. Each layer can exhibit either
a two-cluster state, a periodic traveling wave, or an incoherent state, and these
states can coexist on different scales of subnetwork sizes.
PMID- 29347360
TI - Incorporation of velocity-dependent restitution coefficient and particle surface
friction into kinetic theory for modeling granular flow cooling.
AB - Kinetic theory (KT) has been successfully used to model rapid granular flows in
which particle interactions are frictionless and near elastic. However, it fails
when particle interactions become frictional and inelastic. For example, the KT
is not able to accurately predict the free cooling process of a vibrated granular
medium that consists of inelastic frictional particles under microgravity. The
main reason that the classical KT fails to model these flows is due to its
inability to account for the particle surface friction and its inelastic
behavior, which are the two most important factors that need be considered in
modeling collisional granular flows. In this study, we have modified the KT model
that is able to incorporate these two factors. The inelasticity of a particle is
considered by establishing a velocity-dependent expression for the restitution
coefficient based on many experimental studies found in the literature, and the
particle friction effect is included by using a tangential restitution
coefficient that is related to the particle friction coefficient. Theoretical
predictions of the free cooling process by the classical KT and the improved KT
are compared with the experimental results from a study conducted on an airplane
undergoing parabolic flights without the influence of gravity [Y. Grasselli, G.
Bossis, and G. Goutallier, Europhys. Lett. 86, 60007 (2009)10.1209/0295
5075/86/60007]. Our results show that both the velocity-dependent restitution
coefficient and the particle surface friction are important in predicting the
free cooling process of granular flows; the modified KT model that integrates
these two factors is able to improve the simulation results and leads to better
agreement with the experimental results.
PMID- 29347361
TI - Folding time dependence of the motions of a molecular motor in an amorphous
medium.
AB - We investigate the dependence of the displacements of a molecular motor embedded
inside a glassy material on its folding characteristic time tau_{f}. We observe
two different time regimes. For slow foldings (regime I) the diffusion evolves
very slowly with tau_{f}, while for rapid foldings (regime II) the diffusion
increases strongly with tau_{f}(D~tau_{f}^{-2}), suggesting two different
physical mechanisms. We find that in regime I the motor's displacement during the
folding process is counteracted by a reverse displacement during the unfolding,
while in regime II this counteraction is much weaker. We notice that regime I
behavior is reminiscent of the scallop theorem that holds for larger motors in a
continuous medium. We find that the difference in the efficiency of the motor's
motion explains most of the observed difference between the two regimes. For fast
foldings the motor trajectories differ significantly from the opposite
trajectories induced by the following unfolding process, resulting in a more
efficient global motion than for slow foldings. This result agrees with the
fluctuation theorems expectation for time reversal mechanisms. In agreement with
the fluctuation theorems we find that the motors are unexpectedly more efficient
when they are generating more entropy, a result that can be used to increase
dramatically the motor's motion.
PMID- 29347362
TI - Phase transitions in a system of long rods on two-dimensional lattices by means
of information theory.
AB - The orientational phase transitions that occur in the deposition of longitudinal
polymers of length k (in terms of lattice units) are characterized by information
theory techniques. We calculate the absolute value of an order parameter delta,
which weights the relative orientations of the deposited rods, which varies
between 0.0 (random orientation) and 1.0 (fully oriented in either of the two
equivalent directions in an L*L square lattice). A Monte Carlo (MC) algorithm is
implemented to induce a dynamics allowing for accommodation of the rods for any
given density or coverage theta (ratio of the occupied sites over all the sites
in the lattice). The files storing delta(t) (with time t measured in MC steps)
are then treated by data recognizer wlzip based on data compressor techniques
yielding the information content measured by a parameter eta(theta). This allows
us to recognize two maxima separated by a well-defined minimum for eta(theta)
provided k>=7. The first maximum is associated with an isotropic-nematic (I-N)
phase transition occurring at intermediate density, while the second maximum is
associated with some kind of nematic-isotropic transition at high coverage. In
the cases of k<7, the curves for eta(theta) are almost constant, presenting a
very broad maximum which can hardly be associated with a phase transition. The
study varies L and k, allowing for a basic scaling of the found critical
densities towards the thermodynamic limit. These calculations confirm the
tendency obtained by different methods in the case of the intermediate-density I
N phase transition, while this tendency is established here in the case of the
high-density phase transition.
PMID- 29347363
TI - Control of viscous fingering by nanoparticles.
AB - A substantial viscosity increase by the addition of a low dose of nanoparticles
to the base fluids can well influence the dynamics of viscous fingering. There is
a lack of detailed theoretical studies that address the effect of the presence of
nanoparticles on unstable miscible displacements. In this study, the impact of
nonreactive nanoparticle presence on the stability and subsequent mixing of an
originally unstable binary system is examined using linear stability analysis
(LSA) and pseudospectral-based direct numerical simulations (DNS). We have
parametrized the role of both nondepositing and depositing nanoparticles on the
stability of miscible displacements using the developed static and dynamic
parametric analyses. Our results show that nanoparticles have the potential to
weaken the instabilities of an originally unstable system. Our LSA and DNS
results also reveal that nondepositing nanoparticles can be used to fully
stabilize an originally unstable front while depositing particles may act as
temporary stabilizers whose influence diminishes in the course of time. In
addition, we explain the existing inconsistencies concerning the effect of the
nanoparticle diffusion coefficient on the dynamics of the system. This study
provides a basis for further research on the application of nanoparticles for
control of viscosity-driven instabilities.
PMID- 29347364
TI - Distribution of shortest cycle lengths in random networks.
AB - We present analytical results for the distribution of shortest cycle lengths
(DSCL) in random networks. The approach is based on the relation between the DSCL
and the distribution of shortest path lengths (DSPL). We apply this approach to
configuration model networks, for which analytical results for the DSPL were
obtained before. We first calculate the fraction of nodes in the network which
reside on at least one cycle. Conditioning on being on a cycle, we provide the
DSCL over ensembles of configuration model networks with degree distributions
which follow a Poisson distribution (Erdos-Renyi network), degenerate
distribution (random regular graph), and a power-law distribution (scale-free
network). The mean and variance of the DSCL are calculated. The analytical
results are found to be in very good agreement with the results of computer
simulations.
PMID- 29347365
TI - Solution x-ray scattering and structure formation in protein dynamics.
AB - We propose a computationally effective approach that builds on Landau mean-field
theory in combination with modern nonequilibrium statistical mechanics to model
and interpret protein dynamics and structure formation in small- to wide-angle x
ray scattering (S/WAXS) experiments. We develop the methodology by analyzing
experimental data in the case of Engrailed homeodomain protein as an example. We
demonstrate how to interpret S/WAXS data qualitatively with a good precision and
over an extended temperature range. We explain experimental observations in terms
of protein phase structure, and we make predictions for future experiments and
for how to analyze data at different ambient temperature values. We conclude that
the approach we propose has the potential to become a highly accurate,
computationally effective, and predictive tool for analyzing S/WAXS data. For
this, we compare our results with those obtained previously in an all-atom
molecular dynamics simulation.
PMID- 29347366
TI - Switching synchronization in one-dimensional memristive networks: An exact
solution.
AB - We study a switching synchronization phenomenon taking place in one-dimensional
memristive networks when the memristors switch from the high- to low-resistance
state. It is assumed that the distributions of threshold voltages and switching
rates of memristors are arbitrary. Using the Laplace transform, a set of
nonlinear equations describing the memristors dynamics is solved exactly, without
any approximations. The time dependencies of memristances are found, and it is
shown that the voltage falls across memristors are proportional to their
threshold voltages. A compact expression for the network switching time is
derived.
PMID- 29347368
TI - Three-scale analysis of the permeability of a natural shale.
AB - The macroscopic permeability of a natural shale is determined by using structural
measurements on three different scales. Transmission electron microscopy yields
two-dimensional (2D) images with pixels smaller than 1 nm; these images are used
to reconstruct 3D nanostructures. Three-dimensional focused ion beam-scanning
electron microscopy (5.95- to 8.48-nm voxel size) provides 3D mesoscale pores of
limited relative volume (1.71-5.9%). Micro-computed tomography (700-nm voxel
size) provides information on the mineralogy of the shale, including the pores on
this scale which do not percolate; synthetic 3D media are derived on the
macroscopic scale by a training image technique. Permeability of the nanoscale,
of the mesoscale structures and of their superposition is determined by solving
the Stokes equation and this enables us to estimate the permeabilities of the 700
nm voxels located within the clay matrix. Finally, the Darcy equation is solved
on synthetic 3D macroscale media to obtain the macroscopic permeability which is
found in good agreement with experimental results obtained on the centimetric
scale.
PMID- 29347367
TI - Elastic and viscous properties of the nematic dimer CB7CB.
AB - We present a comprehensive set of measurements of optical, dielectric,
diamagnetic, elastic, and viscous properties in the nematic (N) phase formed by a
liquid crystalline dimer. The studied dimer, 1,7-bis-4-(4'-cyanobiphenyl) heptane
(CB7CB), is composed of two rigid rodlike cyanobiphenyl segments connected by a
flexible aliphatic link with seven methyl groups. CB7CB and other nematic dimers
are of interest due to their tendency to adopt bent configurations and to form
two states possessing a modulated nematic director structure, namely, the twist
bend nematic, N_{TB}, and the oblique helicoidal cholesteric, Ch_{OH}, which
occurs when the achiral dimer is doped with a chiral additive and exposed to an
external electric or magnetic field. We characterize the material parameters as
functions of temperature in the entire temperature range of the N phase,
including the pretransitional regions near the N-N_{TB} and N-to-isotropic (I)
transitions. The splay constant K_{11} is determined by two direct and
independent techniques, namely, detection of the Frederiks transition and
measurement of director fluctuation amplitudes by dynamic light scattering (DLS).
The bend K_{33} and twist K_{22} constants are measured by DLS. K_{33}, being the
smallest of the three constants, shows a strong nonmonotonous temperature
dependence with a negative slope in both N-I and N-N_{TB} pretransitional
regions. The measured ratio K_{11}/K_{22} is larger than 2 in the entire nematic
temperature range. The orientational viscosities associated with splay, twist,
and bend fluctuations in the N phase are comparable to those of nematics formed
by rodlike molecules. All three show strong temperature dependence, increasing
sharply near the N-N_{TB} transition.
PMID- 29347369
TI - Relaxation-type nonlocal inertial-number rheology for dry granular flows.
AB - We propose a constitutive model to describe the nonlocality, hysteresis, and
several flow features of dry granular materials. Taking the well-known inertial
number I as a measure of sheared-induced local fluidization, we derive a
relaxation model for I according to the evolution of microstructure during
avalanche and dissipation processes. The model yields a nonmonotonic flow law for
a homogeneous flow, accounting for hysteretic solid-fluid transition and
intermittency in quasistatic flows. For an inhomogeneous flow, the model predicts
a generalized Bagnold shear stress revealing the interplay of two microscopic
nonlocal mechanisms: collisions among correlated structures and the diffusion of
fluidization within the structures. In describing a uniform flow down an incline,
the model reproduces the hysteretic starting and stopping heights and the
Pouliquen flow rule for mean velocity. Moreover, a dimensionless parameter
reflecting the nonlocal effect on the flow is discovered, which controls the
transition between Bagnold and creeping flow dynamics.
PMID- 29347370
TI - Crucial events, randomness, and multifractality in heartbeats.
AB - We study the connection between multifractality and crucial events.
Multifractality is frequently used as a measure of physiological variability,
where crucial events are known to play a fundamental role in the transport of
information between complex networks. To establish the connection of interest we
focus on the special case of heartbeat time series and on the search for a
diagnostic prescription to distinguish healthy from pathologic subjects. Over the
past 20 years two apparently different diagnostic techniques have been
established: the first is based on the observation that the multifractal spectrum
of healthy patients is broader than the multifractal spectrum of pathologic
subjects; the second is based on the observation that heartbeat dynamics are a
superposition of crucial and uncorrelated Poisson-like events, with pathologic
patients hosting uncorrelated Poisson-like events with larger probability than
the healthy patients. In this paper, we prove that increasing the percentage of
uncorrelated Poisson-like events hosted by heartbeats has the effect of making
their multifractal spectrum narrower, thereby establishing that the two different
diagnostic techniques are compatible with one another and, at the same time,
establishing a dynamic interpretation of multifractal processes that had been
previously overlooked.
PMID- 29347371
TI - Boundary effects in a quasi-two-dimensional driven granular fluid.
AB - The effect of a confining boundary on the spatial variations in granular
temperature of a driven quasi-two-dimensional layer of particles is investigated
experimentally. The radial drop in the relative granular temperature DeltaT/T
exhibits a maximum at intermediate particle numbers which coincides with a
crossover from kinetic to collisional transport of energy. It is also found that
at low particle numbers, the distributions of radial velocities are increasingly
asymmetric as one approaches the boundary. The radial and tangential granular
temperatures split, and in the tails of the radial velocity distribution there is
a higher population of fast moving particles traveling away rather than towards
the boundary.
PMID- 29347372
TI - Lattice Boltzmann heat transfer model for permeable voxels.
AB - We develop a gray-scale lattice Boltzmann (LB) model to study fluid flow combined
with heat transfer for flow through porous media where voxels may be partially
solid (or void). Heat transfer in rocks may lead to deformation, which in turn
can modulate the fluid flow and so has significant contribution to rock
permeability. The LB temperature field is compared to a finite difference
solution of the continuum partial differential equations for fluid flow in a
channel. Excellent quantitative agreement is found for both Poiseuille channel
flow and Brinkman flow. The LB model is then applied to sample porous media such
as packed beds and also more realistic sandstone rock sample, and both the
convective and diffusive regimes are recovered when varying the thermal
diffusivity. It is found that while the rock permeability can be comparatively
small (order milli-Darcy), the temperature field can show significant variation
depending on the thermal convection of the fluid. This LB method has significant
advantages over other numerical methods such as finite and boundary element
methods in dealing with coupled fluid flow and heat transfer in rocks which have
irregular and nonsmooth pore spaces.
PMID- 29347373
TI - Quantum chaos for nonstandard symmetry classes in the Feingold-Peres model of
coupled tops.
AB - We consider two coupled quantum tops with angular momentum vectors L and M. The
coupling Hamiltonian defines the Feingold-Peres model, which is a known paradigm
of quantum chaos. We show that this model has a nonstandard symmetry with respect
to the Altland-Zirnbauer tenfold symmetry classification of quantum systems,
which extends the well-known threefold way of Wigner and Dyson (referred to as
"standard" symmetry classes here). We identify the nonstandard symmetry classes
BDI_{0} (chiral orthogonal class with no zero modes), BDI_{1} (chiral orthogonal
class with one zero mode), and CI (antichiral orthogonal class) as well as the
standard symmetry class AI (orthogonal class). We numerically analyze the
specific spectral quantum signatures of chaos related to the nonstandard
symmetries. In the microscopic density of states and in the distribution of the
lowest positive energy eigenvalue, we show that the Feingold-Peres model follows
the predictions of the Gaussian ensembles of random-matrix theory in the
appropriate symmetry class if the corresponding classical dynamics is chaotic. In
a crossover to mixed and near-integrable classical dynamics, we show that these
signatures disappear or strongly change.
PMID- 29347374
TI - Relative velocities in bidisperse turbulent suspensions.
AB - We investigate the distribution of relative velocities between small heavy
particles of different sizes in turbulence by analyzing a statistical model for
bidisperse turbulent suspensions, containing particles with two different Stokes
numbers. This number, St, is a measure of particle inertia which in turn depends
on particle size. When the Stokes numbers are similar, the distribution exhibits
power-law tails, just as in the case of equal St. The power-law exponent is a
nonanalytic function of the mean Stokes number St[over -], so that the exponent
cannot be calculated in perturbation theory around the advective limit. When the
Stokes-number difference is larger, the power law disappears, but the tails of
the distribution still dominate the relative-velocity moments, if St[over -] is
large enough.
PMID- 29347375
TI - Probing the anomalous dynamical phase in long-range quantum spin chains through
Fisher-zero lines.
AB - Using the framework of infinite matrix product states, the existence of an
anomalous dynamical phase for the transverse-field Ising chain with sufficiently
long-range interactions was first reported in J. C. Halimeh and V. Zauner-Stauber
[Phys. Rev. B 96, 134427 (2017)10.1103/PhysRevB.96.134427], where it was shown
that anomalous cusps arise in the Loschmidt-echo return rate for sufficiently
small quenches within the ferromagnetic phase. In this work we further probe the
nature of the anomalous phase through calculating the corresponding Fisher-zero
lines in the complex time plane. We find that these Fisher-zero lines exhibit a
qualitative difference in their behavior, where, unlike in the case of the
regular phase, some of them terminate before intersecting the imaginary axis,
indicating the existence of smooth peaks in the return rate preceding the cusps.
Additionally, we discuss in detail the infinite matrix product state time
evolution method used to calculate Fisher zeros and the Loschmidt-echo return
rate using the matrix product state transfer matrix. Our work sheds further light
on the nature of the anomalous phase in the long-range transverse-field Ising
chain, while the numerical treatment presented can be applied to more general
quantum spin chains.
PMID- 29347376
TI - Numerical solution of the general coupled nonlinear Schrodinger equations on
unbounded domains.
AB - The numerical solution of the general coupled nonlinear Schrodinger equations on
unbounded domains is considered by applying the artificial boundary method in
this paper. In order to design the local absorbing boundary conditions for the
coupled nonlinear Schrodinger equations, we generalize the unified approach
previously proposed [J. Zhang et al., Phys. Rev. E 78, 026709 (2008)PLEEE81539
375510.1103/PhysRevE.78.026709]. Based on the methodology underlying the unified
approach, the original problem is split into two parts, linear and nonlinear
terms, and we then achieve a one-way operator to approximate the linear term to
make the wave out-going, and finally we combine the one-way operator with the
nonlinear term to derive the local absorbing boundary conditions. Then we reduce
the original problem into an initial boundary value problem on the bounded
domain, which can be solved by the finite difference method. The stability of the
reduced problem is also analyzed by introducing some auxiliary variables. Ample
numerical examples are presented to verify the accuracy and effectiveness of our
proposed method.
PMID- 29347377
TI - Edge instability in incompressible planar active fluids.
AB - Interfacial instability is highly relevant to many important biological
processes. A key example arises in wound healing experiments, which observe that
an epithelial layer with an initially straight edge does not heal uniformly. We
consider the phenomenon in the context of active fluids. Improving upon the
approximation used by Zimmermann, Basan, and Levine [Eur. Phys. J.: Spec. Top.
223, 1259 (2014)1951-635510.1140/epjst/e2014-02189-7], we perform a linear
stability analysis on a two-dimensional incompressible hydrodynamic model of an
active fluid with an open interface. We categorize the stability of the model and
find that for experimentally relevant parameters, fingering instability is always
absent in this minimal model. Our results point to the crucial role of density
variation in the fingering instability in tissue regeneration.
PMID- 29347378
TI - Interfacial mixing in high-energy-density matter with a multiphysics kinetic
model.
AB - We have extended a recently developed multispecies, multitemperature Bhatnagar
Gross-Krook model [Haack et al., J. Stat. Phys. 168, 822 (2017)JSTPBS0022
471510.1007/s10955-017-1824-9], to include multiphysics capabilities that enable
modeling of a wider range of physical conditions. In terms of geometry, we have
extended from the spatially homogeneous setting to one spatial dimension. In
terms of the physics, we have included an atomic ionization model, accurate
collision physics across coupling regimes, self-consistent electric fields, and
degeneracy in the electronic screening. We apply the model to a warm dense matter
scenario in which the ablator-fuel interface of an inertial confinement fusion
target is heated, but for larger length and time scales and for much higher
temperatures than can be simulated using molecular dynamics. Relative to
molecular dynamics, the kinetic model greatly extends the temperature regime and
the spatiotemporal scales over which we are able to model. In our numerical
results we observe hydrogen from the ablator material jetting into the fuel
during the early stages of the implosion and compare the relative size of various
diffusion components (Fickean diffusion, electrodiffusion, and barodiffusion)
that drive this process. We also examine kinetic effects, such as anisotropic
distributions and velocity separation, in order to determine when this problem
can be described with a hydrodynamic model.
PMID- 29347379
TI - Neuronal network model of interictal and recurrent ictal activity.
AB - We propose a neuronal network model which undergoes a saddle node on an invariant
circle bifurcation as the mechanism of the transition from the interictal to the
ictal (seizure) state. In the vicinity of this transition, the model captures
important dynamical features of both interictal and ictal states. We study the
nature of interictal spikes and early warnings of the transition predicted by
this model. We further demonstrate that recurrent seizures emerge due to the
interaction between two networks.
PMID- 29347380
TI - Homoclinic snaking in the discrete Swift-Hohenberg equation.
AB - We consider the discrete Swift-Hohenberg equation with cubic and quintic
nonlinearity, obtained from discretizing the spatial derivatives of the Swift
Hohenberg equation using central finite differences. We investigate the
discretization effect on the bifurcation behavior, where we identify three
regions of the coupling parameter, i.e., strong, weak, and intermediate coupling.
Within the regions, the discrete Swift-Hohenberg equation behaves either
similarly or differently from the continuum limit. In the intermediate coupling
region, multiple Maxwell points can occur for the periodic solutions and may
cause irregular snaking and isolas. Numerical continuation is used to obtain and
analyze localized and periodic solutions for each case. Theoretical analysis for
the snaking and stability of the corresponding solutions is provided in the weak
coupling region.
PMID- 29347381
TI - Maximum entropy modeling of metabolic networks by constraining growth-rate
moments predicts coexistence of phenotypes.
AB - In this work maximum entropy distributions in the space of steady states of
metabolic networks are considered upon constraining the first and second moments
of the growth rate. Coexistence of fast and slow phenotypes, with bimodal flux
distributions, emerges upon considering control on the average growth
(optimization) and its fluctuations (heterogeneity). This is applied to the
carbon catabolic core of Escherichia coli where it quantifies the metabolic
activity of slow growing phenotypes and it provides a quantitative map with
metabolic fluxes, opening the possibility to detect coexistence from flux data. A
preliminary analysis on data for E. coli cultures in standard conditions shows
degeneracy for the inferred parameters that extend in the coexistence region.
PMID- 29347382
TI - Aging in mortal superdiffusive Levy walkers.
AB - A growing body of literature examines the effects of superdiffusive subballistic
movement premeasurement (aging or time lag) on observations arising from single
particle tracking. A neglected aspect is the finite lifetime of these Levy
walkers, be they proteins, cells, or larger structures. We examine the effects of
aging on the motility of mortal walkers, and discuss the means by which permanent
stopping of walkers may be categorized as arising from "natural" death or
experimental artifacts such as low photostability or radiation damage. This is
done by comparison of the walkers' mean squared displacement (MSD) with the front
velocity of propagation of a group of walkers, which is found to be invariant
under time lags. For any running time distribution of a mortal random walker, the
MSD is tempered by the stopping rate theta. This provides a physical
interpretation for truncated heavy-tailed diffusion processes and serves as a
tool by which to better classify the underlying running time distributions of
random walkers. Tempering of aged MSDs raises the issue of misinterpreting
superdiffusive motion which appears Brownian or subdiffusive over certain time
scales.
PMID- 29347383
TI - Wavelet-based regularization of the Galerkin truncated three-dimensional
incompressible Euler flows.
AB - We present numerical simulations of the three-dimensional Galerkin truncated
incompressible Euler equations that we integrate in time while regularizing the
solution by applying a wavelet-based denoising. For this, at each time step, the
vorticity field is decomposed into wavelet coefficients, which are split into
strong and weak coefficients, before reconstructing them in physical space to
obtain the corresponding coherent and incoherent vorticities. Both components are
multiscale and orthogonal to each other. Then, by using the Biot-Savart kernel,
one obtains the coherent and incoherent velocities. Advancing the coherent flow
in time, while filtering out the noiselike incoherent flow, models turbulent
dissipation and corresponds to an adaptive regularization. To track the flow
evolution in both space and scale, a safety zone is added in wavelet coefficient
space to the coherent wavelet coefficients. It is shown that the coherent flow
indeed exhibits an intermittent nonlinear dynamics and a k^{-5/3} energy
spectrum, where k is the wave number, characteristic of three-dimensional
homogeneous isotropic turbulence. Finally, we compare the dynamical and
statistical properties of Euler flows subjected to four kinds of regularizations:
dissipative (Navier-Stokes), hyperdissipative (iterated Laplacian), dispersive
(Euler-Voigt), and wavelet-based regularizations.
PMID- 29347384
TI - Bifurcation analysis and phase diagram of a spin-string model with buckled
states.
AB - We analyze a one-dimensional spin-string model, in which string oscillators are
linearly coupled to their two nearest neighbors and to Ising spins representing
internal degrees of freedom. String-spin coupling induces a long-range
ferromagnetic interaction among spins that competes with a spin-spin
antiferromagnetic coupling. As a consequence, the complex phase diagram of the
system exhibits different flat rippled and buckled states, with first or second
order transition lines between states. This complexity translates to the two
dimensional version of the model, whose numerical solution has been recently used
to explain qualitatively the rippled to buckled transition observed in scanning
tunneling microscopy experiments with suspended graphene sheets. Here we describe
in detail the phase diagram of the simpler one-dimensional model and phase
stability using bifurcation theory. This gives additional insight into the
physical mechanisms underlying the different phases and the behavior observed in
experiments.
PMID- 29347385
TI - Organization and scaling in water supply networks.
AB - Public water supply is one of the society's most vital resources and most costly
infrastructures. Traditional concepts of these networks capture their engineering
identity as isolated, deterministic hydraulic units, but overlook their physics
identity as related entities in a probabilistic, geographic ensemble,
characterized by size organization and property scaling. Although discoveries of
allometric scaling in natural supply networks (organisms and rivers) raised the
prospect for similar findings in anthropogenic supplies, so far such a finding
has not been reported in public water or related civic resource supplies.
Examining an empirical ensemble of large number and wide size range, we show that
water supply networks possess self-organized size abundance and theory-explained
allometric scaling in spatial, infrastructural, and resource- and emission-flow
properties. These discoveries establish scaling physics for water supply networks
and may lead to novel applications in resource- and jurisdiction-scale water
governance.
PMID- 29347386
TI - Finite plateau in spectral gap of polychromatic constrained random networks.
AB - We consider critical behavior in the ensemble of polychromatic Erdos-Renyi
networks and regular random graphs, where network vertices are painted in
different colors. The links can be randomly removed and added to the network
subject to the condition of the vertex degree conservation. In these constrained
graphs we run the Metropolis procedure, which favors the connected unicolor
triads of nodes. Changing the chemical potential, MU, of such triads, for some
wide region of MU, we find the formation of a finite plateau in the number of
intercolor links, which exactly matches the finite plateau in the network
algebraic connectivity (the value of the first nonvanishing eigenvalue of the
Laplacian matrix, lambda_{2}). We claim that at the plateau the spontaneously
broken Z_{2} symmetry is restored by the mechanism of modes collectivization in
clusters of different colors. The phenomena of a finite plateau formation holds
also for polychromatic networks with M>=2 colors. The behavior of polychromatic
networks is analyzed via the spectral properties of their adjacency and Laplacian
matrices.
PMID- 29347387
TI - Anomalous interfacial temperature profile induced by phonon localization.
AB - Through the integration of the power spectral density, we obtain temperature
profiles of both multisegment harmonic and anharmonic systems, showing the
presence of an anomalous negative temperature gradient inside the interfacial
segment. Via investigating patterns of the power spectral density, we found that
the counterintuitive phenomenon comes from the presence of interfacial localized
phonon modes. Two out-band localized modes of the harmonic model, which make no
contributions to local temperature due to the absence of phonon interactions,
result in the concave temperature profile and overcooling effect. For the
anharmonic model, thanks to the phonon-phonon interactions, the localized modes
are excited and make considerable contributions to interfacial temperature, which
is clearly shown by examining the temperature accumulation function. When
anharmonicity is considerably large, the negative temperature gradient is absent
since the localized phonon modes are fully mixed. The presence of localized modes
are evidently demonstrated by the inverse participation ratio and normal mode
analysis for the isolated harmonic model. The localized modes make contribution
to interfacial temperature profiles of the harmonic system when they are excited
in initial conditions of simulations.
PMID- 29347388
TI - Finite volume method for self-consistent field theory of polymers: Material
conservation and application.
AB - For the purpose of checking material conservation of various numerical algorithms
used in the self-consistent-field theory (SCFT) of polymeric systems, we develop
an algebraic method using matrix and bra-ket notation, which traces the
Hermiticity of the product of the volume and evolution matrices. Algebraic tests
for material conservation reveal that the popular pseudospectral method in the
Cartesian grid conserves material perfectly, while the finite-volume method (FVM)
is the proper tool when real-space SCFT with the Crank-Nicolson method is adopted
in orthogonal coordinate systems. We also find that alternating direction
implicit methods combined with the FVM exhibit small mass errors in the SCFT
calculation. By introducing fractional cells in the FVM formulation, accurate
SCFT calculations are performed for systems with irregular geometries and the
results are consistent with previous experimental and theoretical works.
PMID- 29347389
TI - Integral fluctuation theorems for stochastic resetting systems.
AB - We study the stochastic thermodynamics of resetting systems. Violation of
microreversibility means that the well-known derivations of fluctuations theorems
break down for dynamics with resetting. Despite that we show that stochastic
resetting systems satisfy two integral fluctuation theorems. The first is the
Hatano-Sasa relation describing the transition between two steady states. The
second integral fluctuation theorem involves a functional that includes both
dynamical and thermodynamic contributions. We find that the second law-like
inequality found by Fuchs et al. for resetting systems [Europhys. Lett. 113,
60009 (2016)EULEEJ0295-507510.1209/0295-5075/113/60009] can be recovered from
this integral fluctuation theorem with the help of Jensen's inequality.
PMID- 29347390
TI - Coalescing colony model: Mean-field, scaling, and geometry.
AB - We analyze the coalescing model where a 'primary' colony grows and randomly emits
secondary colonies that spread and eventually coalesce with it. This model
describes population proliferation in theoretical ecology, tumor growth, and is
also of great interest for modeling urban sprawl. Assuming the primary colony to
be always circular of radius r(t) and the emission rate proportional to
r(t)^{theta}, where theta>0, we derive the mean-field equations governing the
dynamics of the primary colony, calculate the scaling exponents versus theta, and
compare our results with numerical simulations. We then critically test the
validity of the circular approximation for the colony shape and show that it is
sound for a constant emission rate (theta=0). However, when the emission rate is
proportional to the perimeter, the circular approximation breaks down and the
roughness of the primary colony cannot be discarded, thus modifying the scaling
exponents.
PMID- 29347391
TI - Search efficiency of biased migration towards stationary or moving targets in
heterogeneously structured environments.
AB - Efficient search acts as a strong selective force in biological systems ranging
from cellular populations to predator-prey systems. The search processes commonly
involve finding a stationary or mobile target within a heterogeneously structured
environment where obstacles limit migration. An open generic question is whether
random or directionally biased motions or a combination of both provide an
optimal search efficiency and how that depends on the motility and density of
targets and obstacles. To address this question, we develop a simple model that
involves a random walker searching for its targets in a heterogeneous medium of
bond percolation square lattice and used mean first passage time () as an
indication of average search time. Our analysis reveals a dual effect of
directional bias on the minimum value of . For a homogeneous medium,
directionality always decreases and a pure directional migration (a ballistic
motion) serves as the optimized strategy, while for a heterogeneous environment,
we find that the optimized strategy involves a combination of directed and random
migrations. The relative contribution of these modes is determined by the density
of obstacles and motility of targets. Existence of randomness and motility of
targets add to the efficiency of search. Our study reveals generic and simple
rules that govern search efficiency. Our findings might find application in a
number of areas including immunology, cell biology, ecology, and robotics.
PMID- 29347392
TI - Two-dimensional dynamics of a trapped active Brownian particle in a shear flow.
AB - We model the two-dimensional dynamics of a pointlike artificial microswimmer
diffusing in a harmonic trap subject to the shear flow of a highly viscous
medium. The particle is driven simultaneously by the linear restoring force of
the trap, the drag force exerted by the flow, and the torque due to the shear
gradient. For a Couette flow, elliptical orbits in the noiseless regime, and the
correlation functions between the particle's displacements parallel and
orthogonal to the flow are computed analytically. The effects of thermal
fluctuations (translational) and self-propulsion fluctuations (angular) are
treated separately. Finally, we discuss how to extend our approach to the
diffusion of a microswimmer in a Poiseuille flow. These results provide an
accurate reference solution to investigate, both numerically and experimentally,
hydrodynamics corrections to the diffusion of active matter in confined
geometries.
PMID- 29347393
TI - Ultrasonic waves in classical gases.
AB - The velocity and absorption coefficient for the plane sound waves in a classical
gas are obtained by solving the Boltzmann kinetic equation, which describes the
reaction of the single-particle distribution function to a periodic external
field. Within the linear response theory, the nonperturbative dispersion equation
valid for all sound frequencies is derived and solved numerically. The results
are in agreement with the approximate analytical solutions found for both the
frequent- and rare-collision regimes. These results are also in qualitative
agreement with the experimental data for ultrasonic waves in dilute gases.
PMID- 29347394
TI - Linking biological and physical aging: Dynamical scaling of multicellular
regeneration.
AB - The fight against biological aging (bio-aging) is long-standing, with the focus
of intense research aimed at maintaining high rates of tissue regeneration to
promote health and longevity. Nevertheless, there are overwhelming complexities
associated with the quantitative analysis of aging. In this study, we sought to
quantify bio-aging based on physical aging, by mapping instances of multicellular
regeneration to the relaxation of physical systems. An experiment of delayed
wound healing assays was devised to obtain delay-dependent healing data. The
experiment confirmed the slowdown of healing events, which fitted dynamical
scaling just as relaxation events do in physical aging. The scaling exponent,
which describes the aging rate in physics, is here similarly proposed as an
indicator of the deterioration rate of tissue-regenerative power. Parallel
equation-based and cell-based simulations also revealed that asymmetric cell
cycle-regulatory mechanisms under strong growth-inhibitory conditions
predominantly control the critical slowdown of healing analogous to physical
criticality. By establishing a direct link between physical aging and biological
aging, we are able to estimate the aging rate of tissues and to achieve an
integrated understanding of bio-aging mechanism which may improve the modulation
of regeneration for clinical use.
PMID- 29347395
TI - Scarcity of crossing dependencies: A direct outcome of a specific constraint?
AB - The structure of a sentence can be represented as a network where vertices are
words and edges indicate syntactic dependencies. Interestingly, crossing
syntactic dependencies have been observed to be infrequent in human languages.
This leads to the question of whether the scarcity of crossings in languages
arises from an independent and specific constraint on crossings. We provide
statistical evidence suggesting that this is not the case, as the proportion of
dependency crossings of sentences from a wide range of languages can be
accurately estimated by a simple predictor based on a null hypothesis on the
local probability that two dependencies cross given their lengths. The relative
error of this predictor never exceeds 5% on average, whereas the error of a
baseline predictor assuming a random ordering of the words of a sentence is at
least six times greater. Our results suggest that the low frequency of crossings
in natural languages is neither originated by hidden knowledge of language nor by
the undesirability of crossings per se, but as a mere side effect of the
principle of dependency length minimization.
PMID- 29347396
TI - Diffusiophoresis in nonadsorbing polymer solutions: The Asakura-Oosawa model and
stratification in drying films.
AB - A colloidal particle placed in an inhomogeneous solution of smaller nonadsorbing
polymers will move towards regions of lower polymer concentration in order to
reduce the free energy of the interface between the surface of the particle and
the solution. This phenomenon is known as diffusiophoresis. Treating the polymer
as penetrable hard spheres, as in the Asakura-Oosawa model, a simple analytic
expression for the diffusiophoretic drift velocity can be obtained. In the
context of drying films we show that diffusiophoresis by this mechanism can lead
to stratification under easily accessible experimental conditions. By
stratification we mean spontaneous formation of a layer of polymer on top of a
layer of the colloid. Transposed to the case of binary colloidal mixtures, this
offers an explanation for the stratification observed recently in these systems
[A. Fortini et al., Phys. Rev. Lett. 116, 118301 (2016)PRLTAO0031
900710.1103/PhysRevLett.116.118301]. Our results emphasize the importance of
treating solvent dynamics explicitly in these problems and caution against the
neglect of hydrodynamic interactions or the use of implicit solvent models in
which the absence of solvent backflow results in an unbalanced osmotic force that
gives rise to large but unphysical effects.
PMID- 29347397
TI - Maximum of an Airy process plus Brownian motion and memory in Kardar-Parisi-Zhang
growth.
AB - We obtain several exact results for universal distributions involving the maximum
of the Airy_{2} process minus a parabola and plus a Brownian motion, with
applications to the one-dimensional Kardar-Parisi-Zhang (KPZ) stochastic growth
universality class. This allows one to obtain (i) the universal limit, for large
time separation, of the two-time height correlation for droplet initial
conditions, e.g., C_{infinity}=lim_{t_{2}/t_{1}->+infinity}h(t_{1})h(t_{2})[over
]^{c}/h(t_{1})^{2}[over -]^{c}, with C_{infinity}~0.623, as well as conditional
moments, which quantify ergodicity breaking in the time evolution; (ii) in the
same limit, the distribution of the midpoint position x(t_{1}) of a directed
polymer of length t_{2}; and (iii) the height distribution in stationary KPZ with
a step. These results are derived from the replica Bethe ansatz for the KPZ
continuum equation, with a "decoupling assumption" in the large time limit. They
agree and confirm, whenever they can be compared, with (i) our recent tail
results for two-time KPZ with the work by de Nardis and Le Doussal [J. Stat.
Mech. (2017) 0532121742-546810.1088/1742-5468/aa6bce], checked in experiments
with the work by Takeuchi and co-workers [De Nardis et al., Phys. Rev. Lett. 118,
125701 (2017)PRLTAO0031-900710.1103/PhysRevLett.118.125701] and (ii) a recent
result of Maes and Thiery [J. Stat. Phys. 168, 937 (2017)JSTPBS0022
471510.1007/s10955-017-1839-2] on midpoint position.
PMID- 29347398
TI - Forced underwater laminar flows with active magnetohydrodynamic metamaterials.
AB - Theory and practical implementations for wake-free propulsion systems are
proposed and proven with computational fluid dynamic modeling. Introduced
earlier, the concept of active hydrodynamic metamaterials is advanced by
introducing magnetohydrodynamic metamaterials, structures with custom-designed
volumetric distribution of Lorentz forces acting on a conducting fluid.
Distributions of volume forces leading to wake-free, laminar flows are designed
using multivariate optimization. Theoretical indications are presented that such
flows can be sustained at arbitrarily high Reynolds numbers. Moreover, it is
shown that in the limit Re?10^{2}, a fixed volume force distribution may lead to
a forced laminar flow across a wide range of Re numbers, without the need to
reconfigure the force-generating metamaterial. Power requirements for such a
device are studied as a function of the fluid conductivity. Implications to the
design of distributed propulsion systems underwater and in space are discussed.
PMID- 29347399
TI - Correlation between peak-height modulation and phase lapses in transport through
quantum dots.
AB - We show that two intriguing features of mesoscopic transport, namely, the
modulation of Coulomb blockade peak heights and the transmission phase lapses
occurring between subsequent peaks, are closely related. Our analytic arguments
are corroborated by numerical simulations for chaotic ballistic quantum dots. The
correlations between the two properties are experimentally testable. The
statistical distribution of the partial-width amplitude, at the heart of the
previous relationship, is determined, and its characteristic parameters are
estimated from simple models.
PMID- 29347401
TI - Transport on intermediate time scales in flows with cat's eye patterns.
AB - We consider the advection-diffusion transport of tracers in a one-parameter
family of plane periodic flows where the patterns of streamlines feature regions
of confined circulation in the shape of "cat's eyes," separated by meandering
jets with ballistic motion inside them. By varying the parameter, we proceed from
the regular two-dimensional lattice of eddies without jets to the sinusoidally
modulated shear flow without eddies. When a weak thermal noise is added, i.e., at
large Peclet numbers, several intermediate time scales arise, with qualitatively
and quantitatively different transport properties: depending on the parameter of
the flow, the initial position of a tracer, and the aging time, motion of the
tracers ranges from subdiffusive to superballistic. We report on results of
extensive numerical simulations of the mean-squared displacement for different
initial conditions in ordinary and aged situations. These results are compared
with a theory based on a Levy walk that describes the intermediate-time ballistic
regime and gives a reasonable description of the behavior for a certain class of
initial conditions. The interplay of the walk process with internal circulation
dynamics in the trapped state results at intermediate time scales in nonmonotonic
characteristics of aging not captured by the Levy walk model.
PMID- 29347400
TI - Disordered hyperuniformity in two-component nonadditive hard-disk plasmas.
AB - We study the behavior of a classical two-component ionic plasma made up of
nonadditive hard disks with additional logarithmic Coulomb interactions between
them. Due to the Coulomb repulsion, long-wavelength total density fluctuations
are suppressed and the system is globally hyperuniform. Short-range volume
effects lead to phase separation or to heterocoordination for positive or
negative nonadditivities, respectively. These effects compete with the hidden
long-range order imposed by hyperuniformity. As a result, the critical behavior
of the mixture is modified, with long-wavelength concentration fluctuations
partially damped when the system is charged. It is also shown that the decrease
of configurational entropy due to hyperuniformity originates from contributions
beyond the two-particle level. Finally, despite global hyperuniformity, we show
that in our system the spatial configuration associated with each component
separately is not hyperuniform, i.e., the system is not "multihyperuniform."
PMID- 29347402
TI - Stable lattice Boltzmann model for Maxwell equations in media.
AB - : The present work shows a method for stable simulations via the lattice
Boltzmann (LB) model for electromagnetic waves (EM) transiting homogeneous media.
LB models for such media were already presented in the literature, but they
suffer from numerical instability when the media transitions are sharp. We use
one of these models in the limit of pure vacuum derived from Liu and Yan [Appl.
Math. MODEL: 38, 1710 (2014)AMMODL0307-904X10.1016/j.apm.2013.09.009] and apply
an extension that treats the effects of polarization and magnetization
separately. We show simulations of simple examples in which EM waves travel into
media to quantify error scaling, stability, accuracy, and time scaling. For
conductive media, we use the Strang splitting and check the simulations accuracy
at the example of the skin effect. Like pure EM propagation, the error for the
static limits, which are constructed with a current density added in a first
order scheme, can be less than 1%. The presented method is an easily implemented
alternative for the stabilization of simulation for EM waves propagating in
spatially complex structured media properties and arbitrary transitions.
PMID- 29347403
TI - Influence of periodic external fields in multiagent models with language
dynamics.
AB - We investigate large-scale effects induced by external fields, phenomenologically
interpreted as mass media, in multiagent models evolving with the microscopic
dynamics of the binary naming game. In particular, we show that a single external
field, broadcasting information at regular time intervals, can reverse the
majority opinion of the population, provided the frequency and the effectiveness
of the sent messages lie above well-defined thresholds. We study the phase
structure of the model in the mean field approximation and in numerical
simulations with several network topologies. We also investigate the influence on
the agent dynamics of two competing external fields, periodically broadcasting
different messages. In finite regions of the parameter space we observe periodic
equilibrium states in which the average opinion densities are reversed with
respect to naive expectations. Such equilibria occur in two cases: (i) when the
frequencies of the competing messages are different but close to each other; (ii)
when the frequencies are equal and the relative time shift of the messages does
not exceed half a period. We interpret the observed phenomena as a result of the
interplay between the external fields and the internal dynamics of the agents and
conclude that, depending on the model parameters, the naming game is consistent
with scenarios of first- or second-mover advantage (to borrow an expression from
the jargon of business strategy).
PMID- 29347404
TI - Scale-invariant Green-Kubo relation for time-averaged diffusivity.
AB - In recent years it was shown both theoretically and experimentally that in
certain systems exhibiting anomalous diffusion the time- and ensemble-averaged
mean-squared displacement are remarkably different. The ensemble-averaged
diffusivity is obtained from a scaling Green-Kubo relation, which connects the
scale-invariant nonstationary velocity correlation function with the transport
coefficient. Here we obtain the relation between time-averaged diffusivity,
usually recorded in single-particle tracking experiments, and the underlying
scale-invariant velocity correlation function. The time-averaged mean-squared
displacement is given by ~2D_{nu}t^{beta}Delta^{nu-beta},
where t is the total measurement time and Delta is the lag time. Here nu is the
anomalous diffusion exponent obtained from ensemble-averaged measurements
~t^{nu}, while beta>=-1 marks the growth or decline of the kinetic energy
~t^{beta}. Thus, we establish a connection between exponents that can be
read off the asymptotic properties of the velocity correlation function and
similarly for the transport constant D_{nu}. We demonstrate our results with
nonstationary scale-invariant stochastic and deterministic models, thereby
highlighting that systems with equivalent behavior in the ensemble average can
differ strongly in their time average. If the averaged kinetic energy is finite,
beta=0, the time scaling of and are identical;
however, the time-averaged transport coefficient D_{nu} is not identical to the
corresponding ensemble-averaged diffusion constant.
PMID- 29347405
TI - Revisiting universality of the liquid-gas critical point in two dimensions.
AB - Critical point of liquid-gas (LG) transition does not conform with the paradigm
of spontaneous symmetry breaking because there is no broken symmetry in both
phases. We revisit the conjecture that this critical point belongs to the Ising
class by performing large scale Monte Carlo simulations in two-dimensional free
space in combination with the numerical flowgram method. Our main result is that
the critical indices do agree with the Onsager values within the error of 1%-2%.
This significantly improves the accuracy reported in the literature. The related
problem about the role of higher order odd terms in the (real) phi^{4} field
model as a mapping of the LG transition is addressed too. The scaling dimension
of the phi^{5} term at criticality is shown to be the same as that of the linear
one phi. We suggest that the role of all higher order odd terms at criticality is
simply in generating the linear field operator with the critical dimension
consistent with the Ising universality class.
PMID- 29347406
TI - Fast inverse nonlinear Fourier transformation using exponential one-step methods:
Darboux transformation.
AB - This paper considers the non-Hermitian Zakharov-Shabat (ZS) scattering problem
which forms the basis for defining the SU(2) nonlinear Fourier transformation
(NFT). The theoretical underpinnings of this generalization of the conventional
Fourier transformation are quite well established in the Ablowitz-Kaup-Newell
Segur formalism; however, efficient numerical algorithms that could be employed
in practical applications are still unavailable. In this paper, we present a
unified framework for the forward and inverse NFT using exponential one-step
methods which are amenable to FFT-based fast polynomial arithmetic. Within this
discrete framework, we propose a fast Darboux transformation (FDT) algorithm
having an operational complexity of O(KN+Nlog^{2}N) such that the error in the
computed N-samples of the K-soliton vanishes as O(N^{-p}) where p is the order of
convergence of the underlying one-step method. For fixed N, this algorithm
outperforms the classical DT (CDT) algorithm which has a complexity of O(K^{2}N).
We further present an extension of these algorithms to the general version of DT
which allows one to add solitons to arbitrary profiles that are admissible as
scattering potentials in the ZS problem. The general CDT and FDT algorithms have
the same operational complexity as that of the K-soliton case and the order of
convergence matches that of the underlying one-step method. A comparative study
of these algorithms is presented through exhaustive numerical tests.
PMID- 29347407
TI - Improved thermal lattice Boltzmann model for simulation of liquid-vapor phase
change.
AB - In this paper, an improved thermal lattice Boltzmann (LB) model is proposed for
simulating liquid-vapor phase change, which is aimed at improving an existing
thermal LB model for liquid-vapor phase change [S. Gong and P. Cheng, Int. J.
Heat Mass Transfer 55, 4923 (2012)10.1016/j.ijheatmasstransfer.2012.04.037].
First, we emphasize that the replacement of
?.(lambda?T)/?.(lambda?T)rhoc_{V}rhoc_{V} with ?.(chi?T) is an inappropriate
treatment for diffuse interface modeling of liquid-vapor phase change.
Furthermore, the error terms ?_{t_{0}}(Tv)+?.(Tvv), which exist in the
macroscopic temperature equation recovered from the previous model, are
eliminated in the present model through a way that is consistent with the
philosophy of the LB method. Moreover, the discrete effect of the source term is
also eliminated in the present model. Numerical simulations are performed for
droplet evaporation and bubble nucleation to validate the capability of the model
for simulating liquid-vapor phase change. It is shown that the numerical results
of the improved model agree well with those of a finite-difference scheme.
Meanwhile, it is found that the replacement of
?.(lambda?T)/?.(lambda?T)rhoc_{V}rhoc_{V} with ?.(chi?T) leads to significant
numerical errors and the error terms in the recovered macroscopic temperature
equation also result in considerable errors.
PMID- 29347408
TI - Instabilities in rapid directional solidification under weak flow.
AB - We examine a rapidly solidifying binary alloy under directional solidification
with nonequilibrium interfacial thermodynamics viz. the segregation coefficient
and the liquidus slope are speed dependent and attachment-kinetic effects are
present. Both of these effects alone give rise to (steady) cellular
instabilities, mode S, and a pulsatile instability, mode P. We examine how weak
imposed boundary-layer flow of magnitude |V| affects these instabilities. For
small |V|, mode S becomes a traveling and the flow stabilizes (destabilizes) the
interface for small (large) surface energies. For small |V|, mode P has a
critical wave number that shifts from zero to nonzero giving spatial structure.
The flow promotes this instability and the frequencies of the complex conjugate
pairs each increase (decrease) with flow for large (small) wave numbers. These
results are obtained by regular perturbation theory in powers of V far from the
point where the neutral curves cross, but requires a modified expansion in powers
of V^{1/3} near the crossing. A uniform composite expansion is then obtained
valid for all small |V|.
PMID- 29347409
TI - Bulk and local rheology in a dense and vibrated granular suspension.
AB - In this paper, we investigate experimentally the dynamics of particles in dense
granular suspensions when both shear and external vibrations are applied. We
study in detail how vibrations affect particle reorganization at the local scale
and modify the apparent rheology. The nonlocal nature of the rheology when no
vibrations are applied is evidenced, in agreement with previous numerical studies
from the literature. It is also shown that vibrations induce structural
reorganizations, which tend to homogenize the system and cancel the nonlocal
properties.
PMID- 29347410
TI - Mode-coupling theory for active Brownian particles.
AB - We present a mode-coupling theory (MCT) for the slow dynamics of two-dimensional
spherical active Brownian particles (ABPs). The ABPs are characterized by a self
propulsion velocity v_{0} and by their translational and rotational diffusion
coefficients D_{t} and D_{r}, respectively. Based on the integration-through
transients formalism, the theory requires as input only the equilibrium static
structure factors of the passive system (where v_{0}=0). It predicts a nontrivial
idealized-glass-transition diagram in the three-dimensional parameter space of
density, self-propulsion velocity, and rotational diffusivity that arise because
at high densities, the persistence length of active swimming l_{p}=v_{0}/D_{r}
interferes with the interaction length l_{c} set by the caging of particles.
While the low-density dynamics of ABPs is characterized by a single Peclet number
Pe=v_{0}^{2}/D_{r}D_{t}, close to the glass transition the dynamics is found to
depend on Pe and l_{p} separately. At fixed density, increasing the self
propulsion velocity causes structural relaxation to speed up, while decreasing
the persistence length slows down the relaxation. The active-MCT glass is a
nonergodic state that is qualitatively different from the passive glass. In it,
correlations of initial density fluctuations never fully decay, but also an
infinite memory of initial orientational fluctuations is retained in the
positions.
PMID- 29347411
TI - Complete analysis of ensemble inequivalence in the Blume-Emery-Griffiths model.
AB - We study inequivalence of canonical and microcanonical ensembles in the mean
field Blume-Emery-Griffiths model. This generalizes previous results obtained for
the Blume-Capel model. The phase diagram strongly depends on the value of the
biquadratic exchange interaction K, the additional feature present in the Blume
Emery-Griffiths model. At small values of K, as for the Blume-Capel model, lines
of first- and second-order phase transitions between a ferromagnetic and a
paramagnetic phase are present, separated by a tricritical point whose location
is different in the two ensembles. At higher values of K the phase diagram
changes substantially, with the appearance of a triple point in the canonical
ensemble, which does not find any correspondence in the microcanonical ensemble.
Moreover, one of the first-order lines that starts from the triple point ends in
a critical point, whose position in the phase diagram is different in the two
ensembles. This line separates two paramagnetic phases characterized by a
different value of the quadrupole moment. These features were not previously
studied for other models and substantially enrich the landscape of ensemble
inequivalence, identifying new aspects that had been discussed in a
classification of phase transitions based on singularity theory. Finally, we
discuss ergodicity breaking, which is highlighted by the presence of gaps in the
accessible values of magnetization at low energies: it also displays new
interesting patterns that are not present in the Blume-Capel model.
PMID- 29347412
TI - Observation of structural universality in disordered systems using bulk diffusion
measurement.
AB - We report on an experimental observation of classical diffusion distinguishing
between structural universality classes of disordered systems in one dimension.
Samples of hyperuniform and short-range disorder were designed, characterized by
the statistics of the placement of micrometer-thin parallel permeable barriers,
and the time-dependent diffusion coefficient was measured by NMR methods over
three orders of magnitude in time. The relation between the structural exponent,
characterizing disorder universality class, and the dynamical exponent of the
diffusion coefficient is experimentally verified. The experimentally established
relation between structure and transport exemplifies the hierarchical nature of
structural complexity-dynamics are mainly determined by the universality class,
whereas microscopic parameters affect the nonuniversal coefficients. These
results open the way for noninvasive characterization of structural correlations
in porous media, complex materials, and biological tissues via a bulk diffusion
measurement.
PMID- 29347413
TI - Off-diagonal expansion quantum Monte Carlo.
AB - We propose a Monte Carlo algorithm designed to simulate quantum as well as
classical systems at equilibrium, bridging the algorithmic gap between quantum
and classical thermal simulation algorithms. The method is based on a
decomposition of the quantum partition function that can be viewed as a series
expansion about its classical part. We argue that the algorithm not only provides
a theoretical advancement in the field of quantum Monte Carlo simulations, but is
optimally suited to tackle quantum many-body systems that exhibit a range of
behaviors from "fully quantum" to "fully classical," in contrast to many existing
methods. We demonstrate the advantages, sometimes by orders of magnitude, of the
technique by comparing it against existing state-of-the-art schemes such as path
integral quantum Monte Carlo and stochastic series expansion. We also illustrate
how our method allows for the unification of quantum and classical thermal
parallel tempering techniques into a single algorithm and discuss its practical
significance.
PMID- 29347414
TI - Dynamical density functional theory analysis of the laning instability in sheared
soft matter.
AB - Using dynamical density functional theory (DDFT) methods we investigate the
laning instability of a sheared colloidal suspension. The nonequilibrium ordering
at the laning transition is driven by nonaffine particle motion arising from
interparticle interactions. Starting from a DDFT which incorporates the nonaffine
motion, we perform a linear stability analysis that enables identification of the
regions of parameter space where lanes form. We illustrate our general approach
by applying it to a simple one-component fluid of soft penetrable particles.
PMID- 29347415
TI - Possible mechanism for aligning microscopic flexible filaments predicted using
"caterpillar" hydrodynamics.
AB - We use the "caterpillar" model for accurately calculating the inhomogeneous
hydrodynamic friction along a microscopic slender cylindrical filaments using
Oseen level hydrodynamics. The methodology is applied to study the motion of a
flexible filament in a circularly polarized field. Our results predict that in
dilute solution alignment occurs along the axis of the field. For electric
fields, the strengths and frequencies required are deduced. These are
experimentally accessible. We therefore propose that this is a practical method
for aligning filaments such as microtubules and functionalized carbon nanotubes.
PMID- 29347416
TI - Computational framework for particle and spin simulations based on the stochastic
Galerkin method.
AB - An implementation of the polynomial chaos expansion is introduced as a fast
solver of the equations of beam and spin motion of charged particles in
electromagnetic fields. We show that, based on the stochastic Galerkin method,
our computational framework substantially reduces the required number of tracking
calculations compared to the widely used Monte Carlo method.
PMID- 29347417
TI - Exact solution of the critical Ising model with special toroidal boundary
conditions.
AB - The Ising model in two dimensions with special toroidal boundary conditions is
analyzed. These boundary conditions, which we call duality-twisted boundary
conditions, may be interpreted as inserting a specific defect line ("seam") in
the system, along noncontractible circles of the cylinder, before closing it into
a torus. We derive exact expressions for the eigenvalues of a transfer matrix for
the critical ferromagnetic Ising model on the M*N square lattice wrapped on the
torus with a specific defect line. As a result we have obtained analytically the
partition function for the Ising model with such boundary conditions. In the case
of infinitely long cylinders of circumference L with duality-twisted boundary
conditions we obtain the asymptotic expansion of the free energy and the inverse
correlation lengths. We find that the ratio of subdominant finite-size correction
terms in the asymptotic expansion of the free energy and the inverse correlation
lengths should be universal. We verify such universal behavior in the framework
of a perturbating conformal approach by calculating the universal structure
constant C_{n1n} for descendent states generated by the operator product
expansion of the primary fields. For such states the calculations of an universal
structure constants is a difficult task, since it involves knowledge of the four
point correlation function, which in general is not fixed by conformal invariance
except for some particular cases, including the Ising model.
PMID- 29347418
TI - Preconditioned lattice Boltzmann method for steady flows: A noncascaded central
moments-based approach.
AB - We present a concise yet effective central-moments-based lattice Boltzmann method
with an accelerated convergence to the steady state through preconditioning. It
is demonstrated that the proposed scheme reduces to a slight modification of the
unaccelerated one, as the preconditioning affects only the equilibrium state.
Different from previous efforts carried out within the lattice Boltzmann
community, the present scheme is built on an original model. In fact, the
corresponding collision operator loses the pyramidal orchestrated nature that is
typical of the cascaded scheme, hence we coin the name "noncascaded." Our model
is very general, characterized by highly intelligible formulations, simple to
implement, and it can be derived for any lattice velocity space.
PMID- 29347419
TI - Diverging, but negligible power at Carnot efficiency: Theory and experiment.
AB - We discuss the possibility of reaching the Carnot efficiency by heat engines
(HEs) out of quasistatic conditions at nonzero power output. We focus on several
models widely used to describe the performance of actual HEs. These models
comprise quantum thermoelectric devices, linear irreversible HEs, minimally
nonlinear irreversible HEs, HEs working in the regime of low-dissipation,
overdamped stochastic HEs and an underdamped stochastic HE. Although some of
these HEs can reach the Carnot efficiency at nonzero and even diverging power,
the magnitude of this power is always negligible compared to the maximum power
attainable in these systems. We provide conditions for attaining the Carnot
efficiency in the individual models and explain practical aspects connected with
reaching the Carnot efficiency at large power output. Furthermore, we show how
our findings can be tested in practice using a standard Brownian HE realizable
with available micromanipulation techniques.
PMID- 29347420
TI - Bayesian inference with information content model check for Langevin equations.
AB - The Bayesian data analysis framework has been proven to be a systematic and
effective method of parameter inference and model selection for stochastic
processes. In this work, we introduce an information content model check that may
serve as a goodness-of-fit, like the chi^{2} procedure, to complement
conventional Bayesian analysis. We demonstrate this extended Bayesian framework
on a system of Langevin equations, where coordinate-dependent mobilities and
measurement noise hinder the normal mean-squared displacement approach.
PMID- 29347421
TI - Turing-like structures in a functional model of cortical spreading depression.
AB - Cortical spreading depression (CSD) along with migraine waves and spreading
depolarization events with stroke or injures are the front-line examples of
extreme physiological behaviors of the brain cortex which manifest themselves via
the onset and spreading of localized areas of neuronal hyperactivity followed by
their depression. While much is known about the physiological pathways involved,
the dynamical mechanisms of the formation and evolution of complex spatiotemporal
patterns during CSD are still poorly understood, in spite of the number of
modeling studies that have been already performed. Recently we have proposed a
relatively simple mathematical model of cortical spreading depression which
counts the effects of neurovascular coupling and cerebral blood flow
redistribution during CSD. In the present study, we address the main dynamical
consequences of newly included pathways, namely, the changes in the formation and
propagation speed of the CSD front and the pattern formation features in two
dimensions. Our most notable finding is that the combination of vascular-mediated
spatial coupling with local regulatory mechanisms results in the formation of
stationary Turing-like patterns during a CSD event.
PMID- 29347422
TI - Periodicity in the autocorrelation function as a mechanism for regularly
occurring zero crossings or extreme values of a Gaussian process.
AB - The problem of zero crossings is of great historical prevalence and promises
extensive application. The challenge is to establish precisely how the
autocorrelation function or power spectrum of a one-dimensional continuous random
process determines the density function of the intervals between the zero
crossings of that process. This paper investigates the case where periodicities
are incorporated into the autocorrelation function of a smooth process. Numerical
simulations, and statistics about the number of crossings in a fixed interval,
reveal that in this case the zero crossings segue between a random and
deterministic point process depending on the relative time scales of the periodic
and nonperiodic components of the autocorrelation function. By considering the
Laplace transform of the density function, we show that incorporating correlation
between successive intervals is essential to obtaining accurate results for the
interval variance. The same method enables prediction of the density function
tail in some regions, and we suggest approaches for extending this to cover all
regions. In an ever-more complex world, the potential applications for this scale
of regularity in a random process are far reaching and powerful.
PMID- 29347423
TI - Rayleigh-Taylor instability in accelerated elastic-solid slabs.
AB - We develop the linear theory for the asymptotic growth of the incompressible
Rayleigh-Taylor instability of an accelerated solid slab of density rho_{2},
shear modulus G, and thickness h, placed over a semi-infinite ideal fluid of
density rho_{1}_{l} given l, as well as its fluctuations
encoded in the second cumulant _{l}^{c}. We establish scaling relations
governing the behavior close to the boundary. We then give analytic results for
the Brownian force model, in which the microscopic disorder for each degree of
freedom is a random walk. Finally, we confirm these results with numerical
simulations. To do this properly we elucidate the influence of discretization
effects, which also confirms the assumptions entering into the scaling ansatz.
This allows us to reach the scaling limit already for avalanches of moderate
size. We find excellent agreement for the universal shape and its fluctuations,
including all amplitudes.
PMID- 29347439
TI - Quantum effects and quantum chaos in multidimensional tunneling.
AB - The ground-state energy splitting due to tunneling in two-dimensional double
wells of the form V(x,y)=(x^{2}-R^{2})^{2}/8R^{2}+x^{2}
R^{2}/R^{2}gammay+omega^{2}/2y^{2} is calculated. Several results are reported.
First, we give a systematic WKB expansion of the splitting in series in powers of
R^{-2}, each term of the series being a finite polynomial in gamma^{2}. We find
an ascending sequence of the values of the parameter gamma characterizing the
curvature of the classical path, for which the successive corrections to the
leading order vanish. This effect arises because curvature of the path and
quantum nature of motion cancel each other; it does not appear for one
dimensional double wells. Second, we find that for large curvatures, such as for
those describing the proton transfer in a malonaldehyde and hydroxalate anion,
this expansion is of no practical use. Thus, the WKB expansion is reordered to a
strong coupling form, each term of the series in powers of R^{-2} being an
infinite series in powers of gamma[over -]^{2}, gamma[over -]=gamma/R. Third, we
find that the radius of convergence of the series is determined by the
singularity at gamma[over -]_{s}=omega/2. At the singularity the system changes
its character from being a double well to become a single well. Close to this
singularity the classical action and its first quantum correction are found to be
nonanalytic functions of gamma[over -], most likely of the form [1-(gamma[over
]/gamma[over -]_{s})^{2}]^{alpha}, where alpha=1/2 and alpha=-1/2 for the
classical action and its first quantum correction, respectively. Since in the
semiclassical regime of large R the splitting is exponentially dependent on the
value of the classical action and its first quantum correction, close to the
singularity we establish strong sensitivity of the splitting on slight variations
of the parameter gamma[over -] entering the Hamiltonian linearly.
PMID- 29347440
TI - Cooling beyond the boundary value in supercritical fluids under vibration.
AB - Supercritical fluids when subjected to simultaneous quench and vibration have
been known to cause various intriguing flow phenomena and instabilities depending
on the relative direction of temperature gradient and vibration. Here we describe
a surprising and interesting phenomenon wherein temperature in the fluid falls
below the imposed boundary value when the walls are quenched and the direction of
vibration is normal to the temperature gradient. We define these regions in the
fluid as sink zones, because they act like sink for heat within the fluid domain.
The formation of these zones is first explained using a one-dimensional (1D)
analysis with acceleration in constant direction. Subsequently, the effect of
various boundary conditions and the relative direction of the temperature
gradient to acceleration are analyzed, highlighting the necessary conditions for
the formation of sink zones. It is found that the effect of high compressibility
and the action of self-weight (due to high acceleration) causes the temperature
to change in the bulk besides the usual action of piston effect. This
subsequently affects the overall temperature profile thereby leading to the
formation of sink zones. Though the examined 1D cases differ from the current two
dimensional (2D) cases, owing to the direction of acceleration being normal as
compared to parallel in case of former, the explanations pertaining to 1D cases
are judiciously utilized to elucidate the formation of sink zones in 2D
supercritical fluids subjected to thermal quench and vibrational acceleration.
The appearance of sink zones is found to be dependent on several factors such as
proximity to the critical point and acceleration. A surface three-dimensional
plot illustrating the effect of these parameters on onset time of sink zones is
presented to further substantiate these arguments.
PMID- 29347441
TI - Geometrical interpretation of dynamical phase transitions in boundary-driven
systems.
AB - Dynamical phase transitions are defined as nonanalytic points of the large
deviation function of current fluctuations. We show that for boundary-driven
systems, many dynamical phase transitions can be identified using the geometrical
structure of an effective potential of a Hamiltonian, recovered from the
macroscopic fluctuation theory description. Using this method we identify new
dynamical phase transitions that could not be recovered using existing
perturbative methods. Moreover, using the Hamiltonian picture, an experimental
scheme is suggested to demonstrate an analog of dynamical phase transitions in
linear, rather than exponential, time.
PMID- 29347442
TI - Influence of ligand-receptor interactions on force-extension behavior within the
freely jointed chain model.
AB - We study the influence of receptor-ligand interactions on the force response of
single polymer chains theoretically. The extension of the chain is modeled in
terms of freely jointed chain or elastic freely jointed chain (EFJC) models. The
situation involving noninteracting bonds is solved exactly, while effects of
interactions are treated within a mean-field approximation. The form with shorter
bonds governs the low force situation, while the form with longer bonds is
relevant in the high force regime. We further discuss the accuracy of approximate
relations, which were used to describe the response of the EFJC model.
PMID- 29347443
TI - Microcanonical Szilard engines beyond the quasistatic regime.
AB - We discuss the possibility of extracting energy from a single thermal bath using
microcanonical Szilard engines operating in finite time. This extends previous
works on the topic which are restricted to the quasistatic regime. The feedback
protocol is implemented based on linear response predictions of the excess work.
It is claimed that the underlying mechanism leading to energy extraction does not
violate Liouville's theorem and preserves ergodicity throughout the cycle. We
illustrate our results with several examples including an exactly solvable model.
PMID- 29347444
TI - Theoretical study of the effect of pi^{+}-pi^{+} association in imidazolium ionic
liquids at charged interfaces.
AB - We develop an extended classical density-functional theory to describe clustering
of imidazolium-based cations into linear chains, driven by pi-pi stacking. We
find that the associating system displays a similar short-ranged structure to the
completely dissociated fluid. We also construct a restricted primitive model for
associating ionic species in an RTIL+solvent mixture. The double-layer formed in
these systems exhibits strong overscreening by the cation chains, as expected.
Significantly enhanced capacitance is also observed for the case where
counterions are the associating species. The established density-functional
method can be also used to describe polydisperse polyelectrolyte models.
PMID- 29347445
TI - Mobility-induced persistent chimera states.
AB - We study the dynamics of mobile, locally coupled identical oscillators in the
presence of coupling delays. We find different kinds of chimera states in which
coherent in-phase and antiphase domains coexist with incoherent domains. These
chimera states are dynamic and can persist for long times for intermediate
mobility values. We discuss the mechanisms leading to the formation of these
chimera states in different mobility regimes. This finding could be relevant for
natural and technological systems composed of mobile communicating agents.
PMID- 29347446
TI - Diffusing-wave spectroscopy in a standard dynamic light scattering setup.
AB - Diffusing-wave spectroscopy (DWS) extends dynamic light scattering measurements
to samples with strong multiple scattering. DWS treats the transport of photons
through turbid samples as a diffusion process, thereby making it possible to
extract the dynamics of scatterers from measured correlation functions. The
analysis of DWS data requires knowledge of the path length distribution of
photons traveling through the sample. While for flat sample cells this path
length distribution can be readily calculated and expressed in analytical form;
no such expression is available for cylindrical sample cells. DWS measurements
have therefore typically relied on dedicated setups that use flat sample cells.
Here we show how DWS measurements, in particular DWS-based microrheology
measurements, can be performed in standard dynamic light scattering setups that
use cylindrical sample cells. To do so we perform simple random-walk simulations
that yield numerical predictions of the path length distribution as a function of
both the transport mean free path and the detection angle. This information is
used in experiments to extract the mean-square displacement of tracer particles
in the material, as well as the corresponding frequency-dependent viscoelastic
response. An important advantage of our approach is that by performing
measurements at different detection angles, the average path length through the
sample can be varied. For measurements performed on a single sample cell, this
gives access to a wider range of length and time scales than obtained in a
conventional DWS setup. Such angle-dependent measurements also offer an important
consistency check, as for all detection angles the DWS analysis should yield the
same tracer dynamics, even though the respective path length distributions are
very different. We validate our approach by performing measurements both on
aqueous suspensions of tracer particles and on solidlike gelatin samples, for
which we find our DWS-based microrheology data to be in good agreement with
rheological measurements performed on the same samples.
PMID- 29347447
TI - Modeling correlated bursts by the bursty-get-burstier mechanism.
AB - Temporal correlations of time series or event sequences in natural and social
phenomena have been characterized by power-law decaying autocorrelation functions
with decaying exponent gamma. Such temporal correlations can be understood in
terms of power-law distributed interevent times with exponent alpha and/or
correlations between interevent times. The latter, often called correlated
bursts, has recently been studied by measuring power-law distributed bursty
trains with exponent beta. A scaling relation between alpha and gamma has been
established for the uncorrelated interevent times, while little is known about
the effects of correlated interevent times on temporal correlations. In order to
study these effects, we devise the bursty-get-burstier model for correlated
bursts, by which one can tune the degree of correlations between interevent
times, while keeping the same interevent time distribution. We numerically find
that sufficiently strong correlations between interevent times could violate the
scaling relation between alpha and gamma for the uncorrelated case. A nontrivial
dependence of gamma on beta is also found for some range of alpha. The
implication of our results is discussed in terms of the hierarchical organization
of bursty trains at various time scales.
PMID- 29347448
TI - Infinite cascades of phase transitions in the classical Ising chain.
AB - We report exact results on one of the best studied models in statistical physics:
the classical antiferromagnetic Ising chain in a magnetic field. We show that the
model possesses an infinite cascade of thermal phase transitions (also known as
disorder lines or geometric phase transitions). The phase transition is signaled
by a change of asymptotic behavior of the nonlocal string-string correlation
functions when their monotonic decay becomes modulated by incommensurate
oscillations. The transitions occur for rarefied (m-periodic) strings with
arbitrary odd m. We propose a duality transformation which maps the Ising chain
onto the m-leg Ising tube with nearest-neighbor couplings along the legs and the
plaquette four-spin interactions of adjacent legs. Then the m-string correlation
functions of the Ising chain are mapped onto the two-point spin-spin correlation
functions along the legs of the m-leg tube. We trace the origin of these cascades
of phase transitions to the lines of the Lee-Yang zeros of the Ising chain in m
periodic complex magnetic field, allowing us to relate these zeros to the
observable (and potentially measurable) quantities.
PMID- 29347449
TI - Effective electrostatic interactions in colloid-nanoparticle mixtures.
AB - Interparticle interactions and bulk properties of colloidal suspensions can be
substantially modified by the addition of nanoparticles. Extreme asymmetries in
size and charge between colloidal particles and nanoparticles present severe
computational challenges to molecular-scale modeling of such complex systems. We
present a statistical mechanical theory of effective electrostatic interactions
that can greatly ease large-scale modeling of charged colloid-nanoparticle
mixtures. By applying a sequential coarse-graining procedure, we show that a
multicomponent mixture of charged colloids, nanoparticles, counterions, and
coions can be mapped first onto a binary mixture of colloids and nanoparticles
and then onto a one-component model of colloids alone. In a linear-response
approximation, the one-component model is governed by a single effective pair
potential and a one-body volume energy, whose parameters depend nontrivially on
nanoparticle size, charge, and concentration. To test the theory, we perform
molecular dynamics simulations of the two-component and one-component models and
compute structural properties. For moderate electrostatic couplings, colloid
colloid radial distribution functions and static structure factors agree closely
between the two models, validating the sequential coarse-graining approach.
Nanoparticles of sufficient charge and concentration enhance screening of
electrostatic interactions, weakening correlations between charged colloids and
destabilizing suspensions, consistent with experiments.
PMID- 29347450
TI - Quantum phase transition in an effective three-mode model of interacting bosons.
AB - In this work we study an effective three-mode model describing interacting
bosons. These bosons can be considered as exciton-polaritons in a semiconductor
microcavity at the magic angle. This model exhibits quantum phase transition
(QPT) when the parameters of the corresponding Hamiltonian are continuously
varied. The properties of the Hamiltonian spectrum (e.g., the distance between
two adjacent energy levels) and the phase space structure of the thermodynamic
limit of the model are used to indicate QPT. The relation between spectral
properties of the Hamiltonian and the corresponding classical frame of the
thermodynamic limit of the model is established as indicative of QPT. The average
number of bosons in a specific mode and the entanglement properties of the ground
state as functions of the parameters are used to characterize the order of the
transition and also to construct a phase diagram. Finally, we verify our results
for experimental data obtained for a setting of exciton-polaritons in a
semiconductor microcavity.
PMID- 29347451
TI - Computational investigation of Tb(III) ion line intensities in single-bubble
sonoluminescence.
AB - We perform a computational fluid dynamics simulation of trivalent terbium
[Tb(III)] ion line emissions from single-bubble sonoluminescence (SBSL). Our
simulation includes dynamic boundary conditions as well as the effects of gas
properties and quenching by species, such as nitrite ion (NO_{2}^{-}). Simulation
results demonstrate that when the maximum temperature inside a dimly luminescing
bubble is relatively low, emission peaks from excited Tb(III) ions are prominent
within the emission spectra. As the maximum temperature of the bubble increases,
emission peaks of Tb(III) ions fade away relative to the continuum background
emission. These calculations match observations of Tb(III) line emissions from
SBSL occurring in aqueous solutions of terbium nitrate [Tb(NO_{3})_{3}] under an
argon gas atmosphere. The evolution of the radiation energy spectrum over time
for sonoluminescing bubbles provides a clear mechanism explaining Tb(III)
emission peaks gradually merging into the continuous background emission as the
radiation power increases.
PMID- 29347452
TI - Incorporating Born solvation energy into the three-dimensional Poisson-Nernst
Planck model to study ion selectivity in KcsA K^{+} channels.
AB - Potassium channels are much more permeable to potassium than sodium ions,
although potassium ions are larger and both carry the same positive charge. This
puzzle cannot be solved based on the traditional Poisson-Nernst-Planck (PNP)
theory of electrodiffusion because the PNP model treats all ions as point
charges, does not incorporate ion size information, and therefore cannot
discriminate potassium from sodium ions. The PNP model can qualitatively capture
some macroscopic properties of certain channel systems such as current-voltage
characteristics, conductance rectification, and inverse membrane potential.
However, the traditional PNP model is a continuum mean-field model and has no or
underestimates the discrete ion effects, in particular the ion solvation or self
energy (which can be described by Born model). It is known that the dehydration
effect (closely related to ion size) is crucial to selective permeation in
potassium channels. Therefore, we incorporated Born solvation energy into the PNP
model to account for ion hydration and dehydration effects when passing through
inhomogeneous dielectric channel environments. A variational approach was adopted
to derive a Born-energy-modified PNP (BPNP) model. The model was applied to study
a cylindrical nanopore and a realistic KcsA channel, and three-dimensional finite
element simulations were performed. The BPNP model can distinguish different ion
species by ion radius and predict selectivity for K^{+} over Na^{+} in KcsA
channels. Furthermore, ion current rectification in the KcsA channel was observed
by both the PNP and BPNP models. The I-V curve of the BPNP model for the KcsA
channel indicated an inward rectifier effect for K^{+} (rectification ratio of
~3/2) but indicated an outward rectifier effect for Na^{+} (rectification ratio
of ~1/6).
PMID- 29347453
TI - Tricriticality in the q-neighbor Ising model on a partially duplex clique.
AB - We analyze a modified kinetic Ising model, a so-called q-neighbor Ising model,
with Metropolis dynamics [Phys. Rev. E 92, 052105 (2015)PLEEE81539
375510.1103/PhysRevE.92.052105] on a duplex clique and a partially duplex clique.
In the q-neighbor Ising model each spin interacts only with q spins randomly
chosen from its whole neighborhood. In the case of a duplex clique the change of
a spin is allowed only if both levels simultaneously induce this change. Due to
the mean-field-like nature of the model we are able to derive the analytic form
of transition probabilities and solve the corresponding master equation. The
existence of the second level changes dramatically the character of the phase
transition. In the case of the monoplex clique, the q-neighbor Ising model
exhibits a continuous phase transition for q=3, discontinuous phase transition
for q>=4, and for q=1 and q=2 the phase transition is not observed. On the other
hand, in the case of the duplex clique continuous phase transitions are observed
for all values of q, even for q=1 and q=2. Subsequently we introduce a partially
duplex clique, parametrized by r?[0,1], which allows us to tune the network from
monoplex (r=0) to duplex (r=1). Such a generalized topology, in which a fraction
r of all nodes appear on both levels, allows us to obtain the critical value of
r=r^{*}(q) at which a tricriticality (switch from continuous to discontinuous
phase transition) appears.
PMID- 29347454
TI - Noise-driven neuromorphic tuned amplifier.
AB - We study a simple stochastic model of neuronal excitatory and inhibitory
interactions. The model is defined on a directed lattice and internodes couplings
are modulated by a nonlinear function that mimics the process of synaptic
activation. We prove that such a system behaves as a fully tunable amplifier: the
endogenous component of noise, stemming from finite size effects, seeds a
coherent (exponential) amplification across the chain generating giant
oscillations with tunable frequencies, a process that the brain could exploit to
enhance, and eventually encode, different signals. On a wider perspective, the
characterized amplification process could provide a reliable pacemaking mechanism
for biological systems. The device extracts energy from the finite size bath and
operates as an out of equilibrium thermal machine, under stationary conditions.
PMID- 29347455
TI - Response of jammed packings to thermal fluctuations.
AB - We focus on the response of mechanically stable (MS) packings of frictionless,
bidisperse disks to thermal fluctuations, with the aim of quantifying how
nonlinearities affect system properties at finite temperature. In contrast,
numerous prior studies characterized the structural and mechanical properties of
MS packings of frictionless spherical particles at zero temperature. Packings of
disks with purely repulsive contact interactions possess two main types of
nonlinearities, one from the form of the interaction potential (e.g., either
linear or Hertzian spring interactions) and one from the breaking (or forming) of
interparticle contacts. To identify the temperature regime at which the contact
breaking nonlinearities begin to contribute, we first calculated the minimum
temperatures T_{cb} required to break a single contact in the MS packing for both
single- and multiple-eigenmode perturbations of the T=0 MS packing. We find that
the temperature required to break a single contact for equal velocity-amplitude
perturbations involving all eigenmodes approaches the minimum value obtained for
a perturbation in the direction connecting disk pairs with the smallest overlap.
We then studied deviations in the constant volume specific heat C[over -]_{V} and
deviations of the average disk positions Deltar from their T=0 values in the
temperature regime T_{C[over -]_{V}}100 for linear spring interactions is independent of
system size. This result emphasizes that contact-breaking nonlinearities are
dominant over form nonlinearities in the low-temperature range T_{cb}1 case and in the p<0 case. The
scaling of the optimal mean cost with the number of points is N^{-p/2} for the
assignment and N^{-p} for the matching when p>1, whereas in both cases it is a
constant when p<0. Finally, our predictions are compared with the results of
numerical simulations.
PMID- 29347464
TI - Erosion and deposition processes in surface granular flows.
AB - We report on experiments aiming at characterizing erosion and deposition
processes on a tilted granular bed. We investigate the existence of the neutral
angle, that is, the critical angle at which erosion exactly balances accretion
after the passage of a granular avalanche of a finite mass. Experiments show in
particular that the neutral angle depends on both avalanche mass and shape but is
rather insensitive to the bed length. This result strongly suggests that the
effective friction between the static and mobile granular phases cannot be taken
as an intrinsic property that is only material dependent but should be considered
a flow-dependent property. Interestingly, for a given avalanche mass, the net
erosion rate increases linearly with the angular deviation from the neutral
angle. We also compare our data with the predictions of the erosion-deposition
model introduced by Bouchaud, Cates, Ravi Prakash, and Edwards (BCRE) [J. Phys. I
4, 1283 (1994)JPGCE81155-430410.1051/jp1:1994195]. We show that the predictions
drawn from the modified version of the BCRE model proposed by Boutreux and de
Gennes, in which the local erosion rate between the static and mobile phases is
independent of the flow thickness, are in remarkable agreement with the
experimental results.
PMID- 29347465
TI - Roles of energy eigenstates and eigenvalues in equilibration of isolated quantum
systems.
AB - We show that eigenenergies and energy eigenstates play different roles in the
equilibration process of an isolated quantum system. Their roles are revealed
numerically by exchanging the eigenenergies between an integrable model and a
nonintegrable model. We find that the structure of eigenenergies of a
nonintegrable model characterized by nondegeneracy ensures that quantum revival
occurs rarely whereas the energy eigenstates of a nonintegrable model suppress
the fluctuations for the equilibrated quantum state. Our study is aided with a
quantum entropy that describes how randomly a wave function is distributed in
quantum phase space. We also demonstrate with this quantum entropy the validity
of Berry's conjecture for energy eigenstates. This implies that the energy
eigenstates of a nonintegrable model appear indeed random.
PMID- 29347466
TI - Intermittency and emergence of coherent structures in wave turbulence of a
vibrating plate.
AB - We report numerical investigations of wave turbulence in a vibrating plate. The
possibility to implement advanced measurement techniques and long-time numerical
simulations makes this system extremely valuable for wave turbulence studies. The
purely 2D character of dynamics of the elastic plate makes it much simpler to
handle compared to much more complex 3D physical systems that are typical of geo-
and astrophysical issues (ocean surface or internal waves, magnetized plasmas or
strongly rotating and/or stratified flows). When the forcing is small the
observed wave turbulence is consistent with the predictions of the weak turbulent
theory. Here we focus on the case of stronger forcing for which coherent
structures can be observed. These structures look similar to the folds and D
cones that are commonly observed for strongly deformed static thin elastic sheets
(crumpled paper) except that they evolve dynamically in our forced system. We
describe their evolution and show that their emergence is associated with
statistical intermittency (lack of self similarity) of strongly nonlinear wave
turbulence. This behavior is reminiscent of intermittency in Navier-Stokes
turbulence. Experimental data show hints of the weak to strong turbulence
transition. However, due to technical limitations and dissipation, the strong
nonlinear regime remains out of reach of experiments and therefore has been
explored numerically.
PMID- 29347467
TI - Increased persistence via asynchrony in oscillating ecological populations with
long-range interaction.
AB - Understanding the influence of the structure of a dispersal network on the
species persistence and modeling a realistic species dispersal in nature are two
central issues in spatial ecology. A realistic dispersal structure which favors
the persistence of interacting ecological systems was studied [M. D. Holland and
A. Hastings, Nature (London) 456, 792 (2008)NATUAS0028-083610.1038/nature07395],
where it was shown that a randomization of the structure of a dispersal network
in a metapopulation model of prey and predator increases the species persistence
via clustering, prolonged transient dynamics, and amplitudes of population
fluctuations. In this paper, by contrast, we show that a deterministic network
topology in a metapopulation can also favor asynchrony and prolonged transient
dynamics if species dispersal obeys a long-range interaction governed by a
distance-dependent power law. To explore the effects of power-law coupling, we
take a realistic ecological model, namely, the Rosenzweig-MacArthur model in each
patch (node) of the network of oscillators, and show that the coupled system is
driven from synchrony to asynchrony with an increase in the power-law exponent.
Moreover, to understand the relationship between species persistence and
variations in power-law exponent, we compute a correlation coefficient to
characterize cluster formation, a synchrony order parameter, and median predator
amplitude. We further show that smaller metapopulations with fewer patches are
more vulnerable to extinction as compared to larger metapopulations with a higher
number of patches. We believe that the present work improves our understanding of
the interconnection between the random network and the deterministic network in
theoretical ecology.
PMID- 29347468
TI - Hypernetted-chain-like closure of Ornstein-Zernike equation in multibody
dissipative particle dynamics.
AB - We have derived a hypernetted-chain-like (HNC-like) approximate closure of the
Ornstein-Zernike equation for multibody dissipative particle dynamics (MDPD)
system in which the classic closures are not directly practicable. We first point
out that the Percus's method is applicable to MDPD system in which particles
interact with a density-dependent potential. And then an HNC-like closure is
derived using Percus's idea and the saddle-point approximation of particle free
energy. This HNC-like closure is compared with results of previous researchers,
and in many cases, it demonstrates better agreement with computer simulation
results. The HNC-like closure is used to predict the cluster crystallization in
MDPD. We determine whether the cluster crystallization will happen in a system
utilizing the widely applicable Hansen-Verlet freezing criterion and by observing
the radial distribution function. The conclusions drawn from the results of the
HNC-like closure are in agreement with computer simulation results. We evaluate
different weight functions to determine whether they are prone to cluster
crystallization. A new effective density-dependent pairwise potential is also
proposed to help to explain the tendency to cluster crystallization of MDPD
systems.
PMID- 29347469
TI - Quantum adiabatic protocols using emergent local Hamiltonians.
AB - We present two applications of emergent local Hamiltonians to speed up quantum
adiabatic protocols for isolated noninteracting and weakly interacting fermionic
systems in one-dimensional lattices. We demonstrate how to extract maximal work
from initial band-insulating states, and how to adiabatically transfer systems
from linear and harmonic traps into box traps. Our protocols consist of two
stages. The first one involves a free expansion followed by a quench to an
emergent local Hamiltonian. In the second stage, the emergent local Hamiltonian
is "turned off" quasistatically. For the adiabatic transfer from a harmonic trap,
we consider both zero- and nonzero-temperature initial states.
PMID- 29347470
TI - Microstructure as a function of the grain size distribution for packings of
frictionless disks: Effects of the size span and the shape of the distribution.
AB - This article presents a numerical study of the effects of grain size distribution
(GSD) on the microstructure of two-dimensional packings of frictionless disks.
The GSD is described by a power law with two parameters controlling the size span
and the shape of the distribution. First, several samples are built for each
combination of these parameters. Then, by means of contact dynamics simulations,
the samples are densified in oedometric conditions and sheared in a simple shear
configuration. The microstructure is analyzed in terms of packing fraction, local
ordering, connectivity, and force transmission properties. It is shown that the
microstructure is notoriously affected by both the size span and the shape of the
GSD. These findings confirm recent observations regarding the size span of the
GSD and extend previous works by describing the effects of the GSD shape.
Specifically, we find that if the GSD shape is varied by increasing the
proportion of small grains by a certain amount, it is possible to increase the
packing fraction, increase coordination, and decrease the proportion of floating
particles. Thus, by carefully controlling the GSD shape, it is possible to obtain
systems that are denser and better connected, probably increasing the system's
robustness and optimizing important strength properties such as stiffness,
cohesion, and fragmentation susceptibility.
PMID- 29347471
TI - Linear-shear-current modified Schrodinger equation for gravity waves in finite
water depth.
AB - A nonlinear Schrodinger equation for the propagation of two-dimensional surface
gravity waves on linear shear currents in finite water depth is derived. In the
derivation, linear shear currents are assumed to be a linear combination of depth
uniform currents and constant vorticity. Therefore, the equation includes the
combined effects of depth-uniform currents and constant vorticity. Next, using
the equation, the properties of the modulational instability of gravity waves on
linear shear currents are investigated. It is showed that shear currents
significantly modify the modulational instability properties of weakly nonlinear
waves. Furthermore, the influence of linear shear currents on Peregrine breather
which can be seen as a prototype of freak waves is also studied. It is
demonstrated that depth-uniform opposing currents can reduce the breather
extension in both the time and spatial domain in intermediate water depth, but
following currents has the adverse impact, indicating that a wave packets with
freak waves formed on following currents contain more hazardous waves in finite
water depth. However, the corresponding and coexisting vorticity can counteract
the influence of currents. Additionally, if the water depth is deep enough, shear
currents have negligible effect on the characteristics of Peregrine breathers.
PMID- 29347472
TI - Extinction dynamics from metastable coexistences in an evolutionary game.
AB - Deterministic evolutionary game dynamics can lead to stable coexistences of
different types. Stochasticity, however, drives the loss of such coexistences.
This extinction is usually accompanied by population size fluctuations. We
investigate the most probable extinction trajectory under such fluctuations by
mapping a stochastic evolutionary model to a problem of classical mechanics using
the Wentzel-Kramers-Brillouin (WKB) approximation. Our results show that more
abundant types in a coexistence may be more likely to go extinct first, in good
agreement with previous results. The distance between the coexistence and
extinction points is not a good predictor of extinction either. Instead, the WKB
method correctly predicts the type going extinct first.
PMID- 29347473
TI - Visual evaluation of surface anchoring strength by electrohydrodynamic convection
of a nematic liquid crystal.
AB - Visual evaluation of the surface anchoring energies in a nematic liquid crystal
(LC) cell is characterized by the direction of the convection roll pattern that
appears in the low-frequency conduction regime. The convection roll pattern in a
twisted nematic LC (TNLC) cell is oriented perpendicular to the midplane LC
director dominating the direction of convection flow, and its direction is
determined by the relative surface anchoring energy between two surface
boundaries. Thus the direction of the roll pattern generated at the TNLC cell
with asymmetric LC alignment layers can provide information on the surface
anchoring energies at the two boundaries. We demonstrate a method for determining
the two anchoring energies through a measured midplane LC director applied to the
Ericksen-Leslie equation.
PMID- 29347474
TI - Space-time-modulated stochastic processes.
AB - Starting from the physical problem associated with the Lorentzian transformation
of a Poisson-Kac process in inertial frames, the concept of space-time-modulated
stochastic processes is introduced for processes possessing finite propagation
velocity. This class of stochastic processes provides a two-way coupling between
the stochastic perturbation acting on a physical observable and the evolution of
the physical observable itself, which in turn influences the statistical
properties of the stochastic perturbation during its evolution. The definition of
space-time-modulated processes requires the introduction of two functions: a
nonlinear amplitude modulation, controlling the intensity of the stochastic
perturbation, and a time-horizon function, which modulates its statistical
properties, providing irreducible feedback between the stochastic perturbation
and the physical observable influenced by it. The latter property is the peculiar
fingerprint of this class of models that makes them suitable for extension to
generic curved-space times. Considering Poisson-Kac processes as prototypical
examples of stochastic processes possessing finite propagation velocity, the
balance equations for the probability density functions associated with their
space-time modulations are derived. Several examples highlighting the
peculiarities of space-time-modulated processes are thoroughly analyzed.
PMID- 29347475
TI - Micromechanical model for protein materials: From macromolecules to macroscopic
fibers.
AB - We propose a model for the mechanical behavior of protein materials. Based on a
limited number of experimental macromolecular parameters (persistence and contour
length) we obtain the macroscopic behavior of keratin fibers (human, cow, and
rabbit hair), taking into account the damage and residual stretches effects that
are fundamental in many functions of life. We also show the capability of our
approach to describe the main dissipation and permanent strain effects observed
in the more complex spider silk fibers. The comparison between our results and
the data obtained experimentally from cyclic tests demonstrates that our model is
robust and is able to reproduce with a remarkable accuracy the experimental
behavior of all protein materials we tested.
PMID- 29347476
TI - Avoided level crossings in an elliptic billiard.
AB - In an elliptic billiard, we find avoided level crossings taking place over wide
ranges, which are of a Demkov type for generations of eigenfunctions localized on
an islands chain and its pair unstable periodic orbit. For a proof of the
existence of avoided level crossings, first, we show that the quantized
eigenvalue of the unstable periodic orbit, obtained by the Einstein-Brillouin
Keller quantization rule, passes the eigenvalues of bouncing-ball modes localized
on the unstable periodic orbit after Demkov type avoided level crossings so that
pairs of bouncing-ball modes are sequentially generated. Next, by using a
perturbed Hamiltonian, we show that off-diagonal elements in Hamiltonian are
nonzero, which give rise to an interaction between two eigenfunctions. Last, we
verify that the observed phenomenon is Fermi resonance: that is, the quantum
number difference of two normal modes equals the periodic orbits, where
eigenfunctions are localized after an avoided level crossing.
PMID- 29347477
TI - Early warning signal for interior crises in excitable systems.
AB - The ability to reliably predict critical transitions in dynamical systems is a
long-standing goal of diverse scientific communities. Previous work focused on
early warning signals related to local bifurcations (critical slowing down) and
nonbifurcation-type transitions. We extend this toolbox and report on a
characteristic scaling behavior (critical attractor growth) which is indicative
of an impending global bifurcation, an interior crisis in excitable systems. We
demonstrate our early warning signal in a conceptual climate model as well as in
a model of coupled neurons known to exhibit extreme events. We observed critical
attractor growth prior to interior crises of chaotic as well as strange
nonchaotic attractors. These observations promise to extend the classes of
transitions that can be predicted via early warning signals.
PMID- 29347478
TI - Chaotic behavior in Casimir oscillators: A case study for phase-change materials.
AB - Casimir forces between material surfaces at close proximity of less than 200 nm
can lead to increased chaotic behavior of actuating devices depending on the
strength of the Casimir interaction. We investigate these phenomena for phase
change materials in torsional oscillators, where the amorphous to crystalline
phase transitions lead to transitions between high and low Casimir force and
torque states, respectively, without material compositions. For a conservative
system bifurcation curve and Poincare maps analysis show the absence of chaotic
behavior but with the crystalline phase (high force-torque state) favoring more
unstable behavior and stiction. However, for a nonconservative system chaotic
behavior can take place introducing significant risk for stiction, which is again
more pronounced for the crystalline phase. The latter illustrates the more
general scenario that stronger Casimir forces and torques increase the
possibility for chaotic behavior. The latter is making it impossible to predict
whether stiction or stable actuation will occur on a long-term basis, and it is
setting limitations in the design of micronano devices operating at short-range
nanoscale separations.
PMID- 29347479
TI - Strength distribution of large unidirectional composite patches with realistic
load sharing.
AB - Monte Carlo simulations of the failure of unidirectional fiber composites in a
plane transverse to the fiber direction are performed on much larger patches than
in previous works, assuming a realistic load redistribution scheme from broken to
intact fibers. Computational effort involved in these simulations is
substantially reduced using an algorithm based on the quadtree data structure.
The empirical strength distribution obtained from the simulations has a weak-link
character, regardless of the variability in fiber strengths. The empirical
strength distribution is well captured by a probabilistic model based on the
growth of a tight cluster of fiber breaks. It is also well captured by regarding
composite patch failure as the failure of the weakest equal load-sharing bundle
of a certain size, following Curtin [Phys. Rev. Lett. 80, 1445 (1998)PRLTAO0031
900710.1103/PhysRevLett.80.1445]. The approximate coincidence of these two
predictions identifies the dominant failure mechanism underlying Curtin's
empirical scaling relationship.
PMID- 29347480
TI - Effect of mobility ratio on interaction between the fingers in unstable growth
processes.
AB - We investigate interactions between thin fingers formed as a result of an
instability of an advancing front in growth processes. We show that the fingers
can both attract and repel each other, depending on their lengths and the
mobility ratio between the invading and displaced phase. To understand the origin
of these interactions we introduce a simple resistor model of the fingers. The
predictions of the model are then compared to the numerical simulations of two
unstable growth processes: dissolution of partially cemented rock fracture and
viscous fingering in a regular network of channels.
PMID- 29347481
TI - Effective optimization using sample persistence: A case study on quantum
annealers and various Monte Carlo optimization methods.
AB - We present and apply a general-purpose, multistart algorithm for improving the
performance of low-energy samplers used for solving optimization problems. The
algorithm iteratively fixes the value of a large portion of the variables to
values that have a high probability of being optimal. The resulting problems are
smaller and less connected, and samplers tend to give better low-energy samples
for these problems. The algorithm is trivially parallelizable since each start in
the multistart algorithm is independent, and could be applied to any heuristic
solver that can be run multiple times to give a sample. We present results for
several classes of hard problems solved using simulated annealing, path-integral
quantum Monte Carlo, parallel tempering with isoenergetic cluster moves, and a
quantum annealer, and show that the success metrics and the scaling are improved
substantially. When combined with this algorithm, the quantum annealer's scaling
was substantially improved for native Chimera graph problems. In addition, with
this algorithm the scaling of the time to solution of the quantum annealer is
comparable to the Hamze-de Freitas-Selby algorithm on the weak-strong cluster
problems introduced by Boixo et al. Parallel tempering with isoenergetic cluster
moves was able to consistently solve three-dimensional spin glass problems with
8000 variables when combined with our method, whereas without our method it could
not solve any.
PMID- 29347482
TI - Evolutionary games combining two or three pair coordinations on a square lattice.
AB - We study multiagent logit-rule-driven evolutionary games on a square lattice
whose pair interactions are composed of a maximal number of nonoverlapping
elementary coordination games describing Ising-type interactions between just two
of the available strategies. Using Monte Carlo simulations we investigate the
macroscopic noise-level-dependent behavior of the two- and three-pair games and
the critical properties of the continuous phase transtitions these systems
exhibit. The four-strategy game is shown to be equivalent to a system that
consists of two independent and identical Ising models.
PMID- 29347483
TI - Quantum fidelity approach to the ground-state properties of the one-dimensional
axial next-nearest-neighbor Ising model in a transverse field.
AB - In this work we analyze the ground-state properties of the s=1/2 one-dimensional
axial next-nearest-neighbor Ising model in a transverse field using the quantum
fidelity approach. We numerically determined the fidelity susceptibility as a
function of the transverse field B_{x} and the strength of the next-nearest
neighbor interaction J_{2}, for systems of up to 24 spins. We also examine the
ground-state vector with respect to the spatial ordering of the spins. The ground
state phase diagram shows ferromagnetic, floating, and <2,2> phases, and we
predict an infinite number of modulated phases in the thermodynamic limit (L
>infinity). Paramagnetism only occurs for larger magnetic fields. The transition
lines separating the modulated phases seem to be of second order, whereas the
line between the floating and the <2,2> phases is possibly of first order.
PMID- 29347484
TI - Partial inertia induces additional phase transition in the majority vote model.
AB - Explosive (i.e., discontinuous) transitions have aroused great interest by
manifesting in distinct systems, such as synchronization in coupled oscillators,
percolation regime, absorbing phase transitions, and more recently, the majority
vote model with inertia. In the latter, the model rules are slightly modified by
the inclusion of a term depending on the local spin (an inertial term). In such a
case, Chen et al. [Phys Rev. E 95, 042304 (2017)2470
004510.1103/PhysRevE.95.042304] have found that relevant inertia changes the
nature of the phase transition in complex networks, from continuous to
discontinuous. Here we give a further step by embedding inertia only in vertices
with degree larger than a threshold value k^{*}, being the mean system
degree and k^{*} the fraction restriction. Our results, from mean-field analysis
and extensive numerical simulations, reveal that an explosive transition is
presented in both homogeneous and heterogeneous structures for small and
intermediate k^{*}'s. Otherwise, a large restriction can sustain a discontinuous
transition only in the heterogeneous case. This shares some similarities with
recent results for the Kuramoto model [Phys. Rev. E 91, 022818 (2015)PLEEE81539
375510.1103/PhysRevE.91.022818]. Surprisingly, intermediate restriction and large
inertia are responsible for the emergence of an extra phase, in which the system
is partially synchronized and the classification of phase transition depends on
the inertia and the lattice topology. In this case, the system exhibits two phase
transitions.
PMID- 29347485
TI - Mixing and transport from combined stretching-and-folding and cutting-and
shuffling.
AB - While structures and bifurcations controlling tracer particle transport and
mixing have been studied extensively for systems with only stretching-and
folding, and to a lesser extent for systems with only cutting-and-shuffling, few
studies have considered systems with a combination of both. We demonstrate two
bifurcations for nonmixing islands associated with elliptic periodic points that
only occur in systems with combined cutting-and-shuffling and stretching-and
folding, using as an example a map approximating biaxial rotation of a less-than
half-full spherical granular tumbler. First, we characterize a bifurcation of
elliptic island containment, from containment by manifolds associated with
hyperbolic periodic points to containment by cutting line tangency. As a result,
the maximum size of the nonmixing region occurs when the island is at the
bifurcation point. We also demonstrate a bifurcation where periodic points are
annihilated by the cutting-and-shuffling action. Chains of elliptic and
hyperbolic periodic points that arise when invariant tori surrounding an elliptic
point break up [according to Kolmogorov-Arnold-Moser (KAM) theory] can annihilate
when they meet a cutting line. Consequently, the Poincare index (a topological
invariant of smooth systems) is not preserved.
PMID- 29347486
TI - Electrostatic double-layer interaction between stacked charged bilayers.
AB - The inapplicability of the DLVO theory to multilayered anionic bilayers is found
in terms of the co-ion-valence dependence of the lamellar repeat distance. Most
of the added salt is expelled from the interlamellar space to the bulk due to the
Gibbs-Donnan effect on multiple bilayers with the bulk. The electrostatic double
layer interaction is well expressed by the formula recently proposed by Trefalt.
The osmotic pressure due to the expelled ions, rather than the van der Waals
interaction, is the main origin of the attractive force between the bilayers.
PMID- 29347487
TI - Nonstationary Markovian replication process causing diverse diffusions.
AB - We introduce a single generative mechanism that can be used to describe diverse
nonstationary diffusions. A nonstationary Markovian replication process for steps
is considered for which we derive analytically the time evolution of the
probability distribution of the walker's displacement and the generalized
telegrapher equation with time-varying coefficients, and we find that diffusivity
can be determined by temporal changes of replication of an immediate step. By
controlling the replications, we realize diverse diffusions such as alternating
diffusion, superdiffusion, subdiffusion, and marginal diffusion, which originate
from oscillating, increasing, decreasing, and slowly increasing or decreasing
replications with time, respectively.
PMID- 29347488
TI - Numerical calculation on a two-step subdiffusion behavior of lateral protein
movement in plasma membranes.
AB - A two-step subdiffusion behavior of lateral movement of transmembrane proteins in
plasma membranes has been observed by using single-molecule experiments. A nested
double-compartment model where large compartments are divided into several
smaller ones has been proposed in order to explain this observation. These
compartments are considered to be delimited by membrane-skeleton "fences" and
membrane-protein "pickets" bound to the fences. We perform numerical simulations
of a master equation using a simple two-dimensional lattice model to investigate
the heterogeneous diffusion dynamics behavior of transmembrane proteins within
plasma membranes. We show that the experimentally observed two-step subdiffusion
process can be described using fence and picket models combined with decreased
local diffusivity of transmembrane proteins in the vicinity of the pickets. This
allows us to explain the two-step subdiffusion behavior without explicitly
introducing nested double compartments.
PMID- 29347489
TI - Entropy of level-cut random Gaussian structures at different volume fractions.
AB - Cutting random Gaussian fields at a given level can create a variety of
morphologically different two- or several-phase structures that have often been
used to describe physical systems. The entropy of such structures depends on the
covariance function of the generating Gaussian random field, which in turn
depends on its spectral density. But the entropy of level-cut structures also
depends on the volume fractions of different phases, which is determined by the
selection of the cutting level. This dependence has been neglected in earlier
work. We evaluate the entropy of several lattice models to show that, even in the
cases of strongly coupled systems, the dependence of the entropy of level-cut
structures on molar fractions of the constituents scales with the simple ideal
noninteracting system formula. In the last section, we discuss the application of
the results to binary or ternary fluids and microemulsions.
PMID- 29347490
TI - Free-energy barriers for crystal nucleation from fluid phases.
AB - Monte Carlo simulations of crystal nuclei coexisting with the fluid phase in
thermal equilibrium in finite volumes are presented and analyzed, for fluid
densities from dense melts to the vapor. Generalizing the lever rule for two
phase coexistence in the canonical ensemble to finite volume, "measurements" of
the nucleus volume together with the pressure and chemical potential of the
surrounding fluid allows us to extract the surface free energy of the nucleus.
Neither the knowledge of the (in general nonspherical) nucleus shape nor of the
angle-dependent interface tension is required for this task. The feasibility of
the approach is demonstrated for a variant of the Asakura-Oosawa model for
colloid-polymer mixtures, which form face-centered cubic colloidal crystals. For
a polymer to colloid size ratio of 0.15, the colloid packing fraction in the
fluid phase can be varied from melt values to zero by the variation of an
effective attractive potential between the colloids. It is found that the
approximation of spherical crystal nuclei often underestimates actual nucleation
barriers significantly. Nucleation barriers are found to scale as
DeltaF^{*}=(4pi/3)^{1/3}gamma[over -](V^{*})^{2/3}+const with the nucleus volume
V^{*}, and the effective surface tension gamma[over -] that accounts implicitly
for the nonspherical shape can be precisely estimated.
PMID- 29347491
TI - Broadening of cyclotron resonance conditions in the relativistic interaction of
an intense laser with overdense plasmas.
AB - The interaction of dense plasmas with an intense laser under a strong external
magnetic field has been investigated. When the cyclotron frequency for the
ambient magnetic field is higher than the laser frequency, the laser's
electromagnetic field is converted to the whistler mode that propagates along the
field line. Because of the nature of the whistler wave, the laser light
penetrates into dense plasmas with no cutoff density, and produces superthermal
electrons through cyclotron resonance. It is found that the cyclotron resonance
absorption occurs effectively under the broadened conditions, or a wider range of
the external field, which is caused by the presence of relativistic electrons
accelerated by the laser field. The upper limit of the ambient field for the
resonance increases in proportion to the square root of the relativistic laser
intensity. The propagation of a large-amplitude whistler wave could raise the
possibility for plasma heating and particle acceleration deep inside dense
plasmas.
PMID- 29347492
TI - Elucidating fluctuating diffusivity in center-of-mass motion of polymer models
with time-averaged mean-square-displacement tensor.
AB - There have been increasing reports that the diffusion coefficient of
macromolecules depends on time and fluctuates randomly. Here a method is
developed to elucidate this fluctuating diffusivity from trajectory data. Time
averaged mean-square displacement (MSD), a common tool in single-particle
tracking (SPT) experiments, is generalized to a second-order tensor with which
both magnitude and orientation fluctuations of the diffusivity can be clearly
detected. This method is used to analyze the center-of-mass motion of four
fundamental polymer models: the Rouse model, the Zimm model, a reptation model,
and a rigid rodlike polymer. It is found that these models exhibit distinctly
different types of magnitude and orientation fluctuations of diffusivity. This is
an advantage of the present method over previous ones, such as the ergodicity
breaking parameter and a non-Gaussian parameter, because with either of these
parameters it is difficult to distinguish the dynamics of the four polymer
models. Also, the present method of a time-averaged MSD tensor could be used to
analyze trajectory data obtained in SPT experiments.
PMID- 29347493
TI - Kinetic theory of shear thickening for a moderately dense gas-solid suspension:
From discontinuous thickening to continuous thickening.
AB - The Enskog kinetic theory for moderately dense gas-solid suspensions under simple
shear flow is considered as a model to analyze the rheological properties of the
system. The influence of the environmental fluid on solid particles is modeled
via a viscous drag force plus a stochastic Langevin-like term. The Enskog
equation is solved by means of two independent but complementary routes: (i)
Grad's moment method and (ii) event-driven Langevin simulation of hard spheres.
Both approaches clearly show that the flow curve (stress-strain rate relation)
depends significantly on the volume fraction of the solid particles. In
particular, as the density increases, there is a transition from the
discontinuous shear thickening (observed in dilute gases) to the continuous shear
thickening for denser systems. The comparison between theory and simulations
indicates that while the theoretical predictions for the kinetic temperature
agree well with simulations for densities phi?0.5, the agreement for the other
rheological quantities (the viscosity, the stress ratio, and the normal stress
differences) is limited to more moderate densities (phi?0.3) if the inelasticity
during collisions between particles is not large.
PMID- 29347494
TI - Forward, backward, and weighted stochastic bridges.
AB - We define stochastic bridges as conditional distributions of stochastic paths
that leave a specified point in phase-space in the past and arrive at another one
in the future. These can be defined relative to either forward or backward
stochastic differential equations and with the inclusion of arbitrary path
dependent weights. The underlying stochastic equations are not the same except in
linear cases. Accordingly, we generalize the theory of stochastic bridges to
include time-reversed and weighted stochastic processes. We show that the
resulting stochastic bridges are identical, whether derived from a forward or a
backward time stochastic process. A numerical algorithm is obtained to sample
these distributions. This technique, which uses partial stochastic equations, is
robust and easily implemented. Examples are given, and comparisons are made to
previous work. In stochastic equations without a gradient drift, our results
confirm an earlier conjecture, while generalizing this to cases with path
dependent weights. An example of a two-dimensional stochastic equation with no
potential solution is analyzed and numerically solved. We show how this method
can treat unexpectedly large excursions occurring during a tunneling or escape
event, in which a system escapes from one quasistable point to arrive at another
one at a later time.
PMID- 29347495
TI - Momentum transport and nonlocality in heat-flux-driven magnetic reconnection in
high-energy-density plasmas.
AB - Recent theory has demonstrated a novel physics regime for magnetic reconnection
in high-energy-density plasmas where the magnetic field is advected by heat flux
via the Nernst effect. Here we elucidate the physics of the electron dissipation
layer in this regime. Through fully kinetic simulation and a generalized Ohm's
law derived from first principles, we show that momentum transport due to a
nonlocal effect, the heat-flux-viscosity, provides the dissipation mechanism for
magnetic reconnection. Scaling analysis, and simulations show that the
reconnection process comprises a magnetic field compression stage and quasisteady
reconnection stage, and the characteristic width of the current sheet in this
regime is several electron mean-free paths. These results show the important
interplay between nonlocal transport effects and generation of anisotropic
components to the distribution function.
PMID- 29347496
TI - Kinetics of lipid-nanoparticle-mediated intracellular mRNA delivery and function.
AB - mRNA delivery into cells forms the basis for one of the new and promising ways to
treat various diseases. Among suitable carriers, lipid nanoparticles (LNPs) with
a size of about 100 nm are now often employed. Despite high current interest in
this area, the understanding of the basic details of LNP-mediated mRNA delivery
and function is limited. To clarify the kinetics of mRNA release from LNPs, the
author uses three generic models implying (i) exponential, (ii) diffusion
controlled, and (iii) detachment-controlled kinetic regimes, respectively.
Despite the distinct differences in these kinetics, the associated transient
kinetics of mRNA translation to the corresponding protein and its degradation are
shown to be not too sensitive to the details of the mRNA delivery by LNPs (or
other nanocarriers). In addition, the author illustrates how this protein may
temporarily influence the expression of one gene or a few equivalent genes. The
analysis includes positive or negative regulation of the gene transcription via
the attachment of the protein without or with positive or negative feedback in
the gene expression. Stable, bistable, and oscillatory schemes have been
scrutinized in this context.
PMID- 29347497
TI - Statistical characterization of discrete conservative systems: The web map.
AB - We numerically study the two-dimensional, area preserving, web map. When the map
is governed by ergodic behavior, it is, as expected, correctly described by
Boltzmann-Gibbs statistics, based on the additive entropic functional
S_{BG}[p(x)]=-k?dxp(x)lnp(x). In contrast, possible ergodicity breakdown and
transitory sticky dynamical behavior drag the map into the realm of generalized q
statistics, based on the nonadditive entropic functional S_{q}[p(x)]=k1
?dx[p(x)]^{q}/q-1 (q?R;S_{1}=S_{BG}). We statistically describe the system
(probability distribution of the sum of successive iterates, sensitivity to the
initial condition, and entropy production per unit time) for typical values of
the parameter that controls the ergodicity of the map. For small (large) values
of the external parameter K, we observe q-Gaussian distributions with q=1.935?
(Gaussian distributions), like for the standard map. In contrast, for
intermediate values of K, we observe a different scenario, due to the fractal
structure of the trajectories embedded in the chaotic sea. Long-standing non
Gaussian distributions are characterized in terms of the kurtosis and the box
counting dimension of chaotic sea.
PMID- 29347498
TI - Plain and oscillatory solitons of the cubic complex Ginzburg-Landau equation with
nonlinear gradient terms.
AB - In this work, we present parameter regions for the existence of stable plain
solitons of the cubic complex Ginzburg-Landau equation (CGLE) with higher-order
terms associated with a fourth-order expansion. Using a perturbation approach
around the nonlinear Schrodinger equation soliton and a full numerical analysis
that solves an ordinary differential equation for the soliton profiles and using
the Evans method in the search for unstable eigenvalues, we have found that the
minimum equation allowing these stable solitons is the cubic CGLE plus a term
known in optics as Raman-delayed response, which is responsible for the redshift
of the spectrum. The other favorable term for the occurrence of stable solitons
is a term that represents the increase of nonlinear gain with higher frequencies.
At the stability boundary, a bifurcation occurs giving rise to stable oscillatory
solitons for higher values of the nonlinear gain. These oscillations can have
very high amplitudes, with the pulse energy changing more than two orders of
magnitude in a period, and they can even exhibit more complex dynamics such as
period-doubling.
PMID- 29347499
TI - Synchronized rotation in swarms of magnetotactic bacteria.
AB - Self-organizing behavior has been widely reported in both natural and artificial
systems, typically distinguishing between temporal organization (synchronization)
and spatial organization (swarming). Swarming has been experimentally observed in
systems of magnetotactic bacteria under the action of external magnetic fields.
Here we present a model of ensembles of magnetotactic bacteria in which
hydrodynamic interactions lead to temporal synchronization in addition to the
swarming. After a period of stabilization during which the bacteria form a
quasiregular hexagonal lattice structure, the entire swarm begins to rotate in a
direction opposite to the direction of the rotation of the magnetic field. We
thus illustrate an emergent mechanism of macroscopic motion arising from the
synchronized microscopic rotations of hydrodynamically interacting bacteria,
reminiscent of the recently proposed concept of swarmalators.
PMID- 29347500
TI - Guidance of microswimmers by wall and flow: Thigmotaxis and rheotaxis of unsteady
squirmers in two and three dimensions.
AB - The motions of an unsteady circular-disk squirmer and a spherical squirmer have
been investigated in the presence of a no-slip infinite wall and a background
shear flow in order to clarify the similarities and differences between two- and
three-dimensional motions. Despite the similar bifurcation structure of the
dynamical system, the stability of the fixed points differs due to the
Hamiltonian structure of the disk squirmer. Once the unsteady oscillating surface
velocity profile is considered, the disk squirmer can behave in a chaotic manner
and cease to be confined in a near-wall region. In contrast, in an unsteady
spherical squirmer, the dynamics is well attracted by a stable fixed point.
Additional wall contact interactions lead to stable fixed points for the disk
squirmer, and, in turn, the surface entrapment of the disk squirmer can be
stabilized, regardless of the existence of the background flow. Finally, we
consider spherical motion under a background flow. The separated time scales of
the surface entrapment (thigmotaxis) and the turning toward the flow direction
(rheotaxis) enable us to reduce the dynamics to two-dimensional phase space, and
simple weather-vane mechanics can predict squirmer rheotaxis. The analogous
structure of the phase plane with the wall contact in two and three dimensions
implies that the two-dimensional disk swimmer successfully captures the nonlinear
interactions, and thus two-dimensional approximation could be useful in designing
microfluidic devices for the guidance of microswimmers and for clarifying the
locomotions in a complex geometry.
PMID- 29347501
TI - Dust coupling parameter of radio-frequency-discharge complex plasma under
microgravity conditions.
AB - Oscillation of particles in a dust crystal formed in a low-pressure radio
frequency gas discharge under microgravity conditions is studied. Analysis of
experimental data obtained in our previous study shows that the oscillations are
highly isotropic and nearly homogeneous in the bulk of a dust crystal;
oscillations of the neighboring particles are significantly correlated. We
demonstrate that the standard deviation of the particle radius vector along with
the local particle number density fully define the coupling parameter of the
particle subsystem. The latter proves to be of the order of 100, which is two
orders of magnitude lower than the coupling parameter estimated for the Brownian
diffusion of particles with the gas temperature. This means significant kinetic
overheating of particles under stationary conditions. A theoretical
interpretation of the large amplitude of oscillation implies the increase of
particle charge fluctuations in the dust crystal. The theoretical estimates are
based on the ionization equation of state for the complex plasma and the equation
for the plasma perturbation evolution. They are shown to match the results of
experimental data processing. Estimated order of magnitude of the coupling
parameter accounts for the existence of the solid-liquid phase transition
observed for similar systems in experiments.
PMID- 29347502
TI - Topography- and topology-driven spreading of non-Newtonian power-law liquids on a
flat and a spherical substrate.
AB - The spreading of a cap-shaped spherical droplet of non-Newtonian power-law
liquids on a flat and a spherical rough and textured substrate is theoretically
studied in the capillary-controlled spreading regime. A droplet whose scale is
much larger than that of the roughness of substrate is considered. The
equilibrium contact angle on a rough substrate is modeled by the Wenzel and the
Cassie-Baxter model. Only the viscous energy dissipation within the droplet
volume is considered, and that within the texture of substrate by imbibition is
neglected. Then, the energy balance approach is adopted to derive the evolution
equation of the contact angle. When the equilibrium contact angle vanishes, the
relaxation of dynamic contact angle theta of a droplet obeys a power-law decay
theta~t^{-alpha} except for the Newtonian and the non-Newtonian shear-thinning
liquid of the Wenzel model on a spherical substrate. The spreading exponent alpha
of the non-Newtonian shear-thickening liquid of the Wenzel model on a spherical
substrate is larger than others. The relaxation of the Newtonian liquid of the
Wenzel model on a spherical substrate is even faster showing the exponential
relaxation. The relaxation of the non-Newtonian shear-thinning liquid of Wenzel
model on a spherical substrate is fastest and finishes within a finite time.
Thus, the topography (roughness) and the topology (flat to spherical) of
substrate accelerate the spreading of droplet.
PMID- 29347503
TI - Impact-induced solidlike behavior and elasticity in concentrated colloidal
suspensions.
AB - Modified drop weight impact tests were performed on SiO_{2}-ethylene glycol
concentrated suspensions. Counterintuitive impact-induced solidlike behavior and
elasticity, causing significant deceleration and rebound of the impactor, were
observed. We provide evidence that the observed large deceleration force on the
impactor mainly originates from the hydrodynamic force, and that the elasticity
arises from the short-range repulsive force of a solvation layer on the particle
surface. This study presents key experimental results to help understand the
mechanisms underlying various stress-induced solidification phenomena.
PMID- 29347504
TI - Ion-beam-plasma interaction effects on electrostatic solitary wave propagation in
ultradense relativistic quantum plasmas.
AB - Understanding the transport properties of charged particle beams is important not
only from a fundamental point of view but also due to its relevance in a variety
of applications. A theoretical model is established in this article, to model the
interaction of a tenuous positively charged ion beam with an ultradense quantum
electron-ion plasma, by employing a rigorous relativistic quantum-hydrodynamic
(fluid plasma) electrostatic model proposed in McKerr et al. [M. McKerr, F. Haas,
and I. Kourakis, Phys. Rev. E 90, 033112 (2014)PLEEE81539
375510.1103/PhysRevE.90.033112]. A nonlinear analysis is carried out to elucidate
the propagation characteristics and the existence conditions of large amplitude
electrostatic solitary waves propagating in the plasma in the presence of the
beam. Anticipating stationary profile excitations, a pseudomechanical energy
balance formalism is adopted to reduce the fluid evolution equation to an
ordinary differential equation. Exact solutions are thus obtained numerically,
predicting localized excitations (pulses) for all of the plasma state variables,
in response to an electrostatic potential disturbance. An ambipolar electric
field form is also obtained. Thorough analysis of the reality conditions for all
variables is undertaken in order to determine the range of allowed values for the
solitonic pulse speed and how it varies as a function of the beam characteristics
(beam velocity and density).
PMID- 29347505
TI - Diffusivity of E. coli-like microswimmers in confined geometries: The role of the
tumbling rate.
AB - We analyzed the effect of confinement on the effective diffusion of a run-and
tumble E. coli-like flagellated microswimmer. We used a simulation protocol where
the run phases are obtained via a fully resolved swimming problem, i.e., Stokes
equations for the fluid coupled with rigid-body dynamics for the microorganism,
while tumbles and collisions with the walls are modeled as random reorientation
of the microswimmer. For weak confinement, the swimmer is trapped in circular
orbits close to the solid walls. In this case, optimal diffusivity is observed
when the tumbling frequency is comparable with the angular velocity of the stable
orbits. For strong confinement, stable circular orbits disappear and the
diffusion coefficient monotonically decreases with the tumbling rate. Our
findings are generic and can be potentially applied to other natural or
artificial chiral microswimmers that follow circular trajectories close to an
interface or in confined geometries.
PMID- 29347506
TI - Energy transport in the presence of long-range interactions.
AB - We study energy transport in the paradigmatic Hamiltonian mean-field (HMF) model
and other related long-range interacting models using molecular dynamics
simulations. We show that energy diffusion in the HMF model is subdiffusive in
nature, which confirms a recently obtained intriguing result that, despite being
globally interacting, this model is a thermal insulator in the thermodynamic
limit. Surprisingly, when additional nearest-neighbor interactions are introduced
to the HMF model, an energy superdiffusion is observed. We show that these
results can be consistently explained by studying energy localization due to
thermally generated intrinsic localized excitation modes (discrete breathers) in
nonlinear discrete systems. Our analysis for the HMF model can also be readily
extended to more generic long-range interacting models where the interaction
strength decays algebraically with the (shortest) distance between two lattice
sites. This reconciles many of the apparently counterintuitive results presented
recently [C. Olivares and C. Anteneodo, Phys. Rev. E 94, 042117 (2016)2470
004510.1103/PhysRevE.94.042117; D. Bagchi, Phys. Rev. E 95, 032102 (2017)2470
004510.1103/PhysRevE.95.032102] concerning energy transport in two such long
range interacting models.
PMID- 29347507
TI - Predictability and strength of a heterogeneous system: The role of system size
and disorder.
AB - In this paper, I have studied the effect of disorder (delta) and system size (L)
in a fiber bundle model with a certain range R of stress redistribution. The
strength of the bundle as well as the failure abruptness is observed with varying
disorder, stress release range, and system sizes. With a local stress
concentration, the strength of the bundle is observed to decrease with system
size. The behavior of such decrements changes drastically as disorder strength is
tuned. At moderate disorder, sigma_{c} scales with the system size as
sigma_{c}~1/logL. In low disorder, where the brittle response is highly expected,
the strength decreases in a scale-free manner (sigma_{c}~1/L). With increasing L
and R, the model approaches the thermodynamic limit and the mean-field limit,
respectively. A detailed study shows different limits of the model and the
corresponding modes of failure on the plane of the above-mentioned parameters
(delta,L, and R).
PMID- 29347508
TI - Publisher's Note: Generalized model for k-core percolation and interdependent
networks [Phys. Rev. E 96, 032317 (2017)].
AB - This corrects the article DOI: 10.1103/PhysRevE.96.032317.
PMID- 29347509
TI - Diversity of charge orderings in correlated systems.
AB - The phenomenon associated with inhomogeneous distribution of electron density is
known as a charge ordering. In this work, we study the zero-bandwidth limit of
the extended Hubbard model, which can be considered as a simple effective model
of charge ordered insulators. It consists of the on-site interaction U and the
intersite density-density interactions W_{1} and W_{2} between nearest neighbors
and next-nearest neighbors, respectively. We derived the exact ground state
diagrams for different lattice dimensionalities and discuss effects of small
finite temperatures in the limit of high dimensions. In particular, we estimated
the critical interactions for which new ordered phases emerge (laminar or stripe
and four-sublattice-type). Our analysis show that the ground state of the model
is highly degenerated. One of the most intriguing finding is that the nonzero
temperature removes these degenerations.
PMID- 29347510
TI - Clustering spectrum of scale-free networks.
AB - Real-world networks often have power-law degrees and scale-free properties, such
as ultrasmall distances and ultrafast information spreading. In this paper, we
study a third universal property: three-point correlations that suppress the
creation of triangles and signal the presence of hierarchy. We quantify this
property in terms of c[over -](k), the probability that two neighbors of a degree
k node are neighbors themselves. We investigate how the clustering spectrum
k?c[over -](k) scales with k in the hidden-variable model and show that c[over
](k) follows a universal curve that consists of three k ranges where c[over -](k)
remains flat, starts declining, and eventually settles on a power-law c[over
](k)~k^{-alpha} with alpha depending on the power law of the degree distribution.
We test these results against ten contemporary real-world networks and explain
analytically why the universal curve properties only reveal themselves in large
networks.
PMID- 29347511
TI - Design of coupling parameters for inducing amplitude death in Cartesian product
networks of delayed coupled oscillators.
AB - The present study investigates amplitude death in Cartesian product networks of
two subnetworks, where each subnetwork has a different coupling delay. The
property of the Cartesian product helps us to analyze the stability of amplitude
death. Our analysis reveals that amplitude death can occur for long coupling
delays if there is a suitable difference in the coupling delays in the two
subnetworks. Furthermore, based on the edge theorem in robust control theory, we
propose two design procedures of coupling parameters for inducing amplitude death
in the Cartesian product networks. Our procedures do not require any information
of topologies of the subnetworks. The validity of these procedures is numerically
confirmed.
PMID- 29347512
TI - Symmetry breaking in two interacting populations of quadratic integrate-and-fire
neurons.
AB - We analyze the dynamics of two coupled identical populations of quadratic
integrate-and-fire neurons, which represent the canonical model for class I
neurons near the spiking threshold. The populations are heterogeneous; they
include both inherently spiking and excitable neurons. The coupling within and
between the populations is global via synapses that take into account the finite
width of synaptic pulses. Using a recently developed reduction method based on
the Lorentzian ansatz, we derive a closed system of equations for the neuron's
firing rates and the mean membrane potentials in both populations. The reduced
equations are exact in the infinite-size limit. The bifurcation analysis of the
equations reveals a rich variety of nonsymmetric patterns, including a splay
state, antiphase periodic oscillations, chimera-like states, and chaotic
oscillations as well as bistabilities between various states. The validity of the
reduced equations is confirmed by direct numerical simulations of the finite-size
networks.
PMID- 29347513
TI - Coherent motion of chaotic attractors.
AB - We report a simple model of two drive-response-type coupled chaotic oscillators,
where the response system copies the nonlinearity of the driver system. It leads
to a coherent motion of the trajectories of the coupled systems that establishes
a constant separating distance in time between the driver and the response
attractors, and their distance depends upon the initial state. The coupled system
responds to external obstacles, modeled by short-duration pulses acting either on
the driver or the response system, by a coherent shifting of the distance, and it
is able to readjust their distance as and when necessary via mutual exchange of
feedback information. We confirm these behaviors with examples of a jerk system,
the paradigmatic Rossler system, a tunnel diode system and a Josephson junction
based jerk system, analytically, to an extent, and mostly numerically.
PMID- 29347514
TI - Pinning of a drop by a junction on an incline.
AB - The shape of a drop pinned on an inclined substrate is a long-standing problem
where the complexity of real surfaces, with heterogeneities and hysteresis, makes
it complicated to understand the mechanisms behind the phenomena. Here we
consider the simple case of a drop pinned on an incline at the junction between a
hydrophilic half plane (the top half) and a hydrophobic one (the bottom half).
Relying on the equilibrium equations deriving from the balance of forces, we
exhibit three scenarios depending on the way the contact line of the drop on the
substrate either simply leans against the junction or overfills (partly or fully)
into the hydrophobic side. We draw some conclusions on the geometry of the
overlap and the stability of these tentative equilibrium states. In the
corresponding retention force factor, we find that a major role is played by the
wetted length of the junction line, in the spirit of Furmidge's observations. The
predictions of the theory are compared with extensive molecular dynamics
simulations.
PMID- 29347515
TI - Transient response in granular quasi-two-dimensional bounded heap flow.
AB - We study the transition between steady flows of noncohesive granular materials in
quasi-two-dimensional bounded heaps by suddenly changing the feed rate. In both
experiments and simulations, the primary feature of the transition is a wedge of
flowing particles that propagates downstream over the rising free surface with a
wedge front velocity inversely proportional to the square root of time. An
additional longer duration transient process continues after the wedge front
reaches the downstream wall. The entire transition is well modeled as a moving
boundary problem with a diffusionlike equation derived from local mass balance
and a local relation between the flux and the surface slope.
PMID- 29347516
TI - Resonant activation of population extinctions.
AB - Understanding the mechanisms governing population extinctions is of key
importance to many problems in ecology and evolution. Stochastic factors are
known to play a central role in extinction, but the interactions between a
population's demographic stochasticity and environmental noise remain poorly
understood. Here we model environmental forcing as a stochastic fluctuation
between two states, one with a higher death rate than the other. We find that, in
general, there exists a rate of fluctuations that minimizes the mean time to
extinction, a phenomenon previously dubbed "resonant activation." We develop a
heuristic description of the phenomenon, together with a criterion for the
existence of resonant activation. Specifically, the minimum extinction time
arises as a result of the system approaching a scenario wherein the severity of
rare events is balanced by the time interval between them. We discuss our
findings within the context of more general forms of environmental noise and
suggest potential applications to evolutionary models.
PMID- 29347517
TI - Embedding the dynamics of a single delay system into a feed-forward ring.
AB - We investigate the relation between the dynamics of a single oscillator with
delayed self-feedback and a feed-forward ring of such oscillators, where each
unit is coupled to its next neighbor in the same way as in the self-feedback
case. We show that periodic solutions of the delayed oscillator give rise to
families of rotating waves with different wave numbers in the corresponding ring.
In particular, if for the single oscillator the periodic solution is resonant to
the delay, it can be embedded into a ring with instantaneous couplings. We
discover several cases where the stability of a periodic solution for the single
unit can be related to the stability of the corresponding rotating wave in the
ring. As a specific example, we demonstrate how the complex bifurcation scenario
of simultaneously emerging multijittering solutions can be transferred from a
single oscillator with delayed pulse feedback to multijittering rotating waves in
a sufficiently large ring of oscillators with instantaneous pulse coupling.
Finally, we present an experimental realization of this dynamical phenomenon in a
system of coupled electronic circuits of FitzHugh-Nagumo type.
PMID- 29347518
TI - Similarity of ensembles of trajectories of reversible and irreversible growth
processes.
AB - Models of bacterial growth tend to be "irreversible," allowing for the number of
bacteria in a colony to increase but not to decrease. By contrast, models of
molecular self-assembly are usually "reversible," allowing for the addition and
removal of particles to a structure. Such processes differ in a fundamental way
because only reversible processes possess an equilibrium. Here we show at the
mean-field level that dynamic trajectories of reversible and irreversible growth
processes are similar in that both feel the influence of attractors, at which
growth proceeds without limit but the intensive properties of the system are
invariant. Attractors of both processes undergo nonequilibrium phase transitions
as model parameters are varied, suggesting a unified way of describing typical
properties of reversible and irreversible growth. We also establish a connection
at the mean-field level between an irreversible model of growth (the magnetic
Eden model) and the equilibrium Ising model, supporting the findings made by
other authors using numerical simulations.
PMID- 29347519
TI - Environmental rocking ratchet: Environmental rectification by a harmonically
driven avoided crossing.
AB - We propose a rocking ratchet designed as a symmetric quantum two-state system
driven by a single periodic harmonic force and influenced symmetrically by
thermal fluctuations. We show that the necessary broken symmetry can dynamically
be achieved by a thermal environment that couples to the energy difference
between the two states and the tunnel coupling between them. The quantum two
state system is driven by the harmonic periodic drive through its avoided
crossing. The correspondingly driven dissipative quantum dynamics results on
average in a finite population difference between both states. This then causes
directed particle transport.
PMID- 29347520
TI - Relativistic analysis of stochastic kinematics.
AB - The relativistic analysis of stochastic kinematics is developed in order to
determine the transformation of the effective diffusivity tensor in inertial
frames. Poisson-Kac stochastic processes are initially considered. For one
dimensional spatial models, the effective diffusion coefficient measured in a
frame Sigma moving with velocity w with respect to the rest frame of the
stochastic process is inversely proportional to the third power of the Lorentz
factor gamma(w)=(1-w^{2}/c^{2})^{-1/2}. Subsequently, higher-dimensional
processes are analyzed and it is shown that the diffusivity tensor in a moving
frame becomes nonisotropic: The diffusivities parallel and orthogonal to the
velocity of the moving frame scale differently with respect to gamma(w). The
analysis of discrete space-time diffusion processes permits one to obtain a
general transformation theory of the tensor diffusivity, confirmed by several
different simulation experiments. Several implications of the theory are also
addressed and discussed.
PMID- 29347521
TI - Inverse problem for multispecies ferromagneticlike mean-field models in phase
space with many states.
AB - In this paper we solve the inverse problem for the Curie-Weiss model and its
multispecies version when multiple thermodynamic states are present as in the low
temperature phase where the phase space is clustered. The inverse problem
consists of reconstructing the model parameters starting from configuration data
generated according to the distribution of the model. We demonstrate that,
without taking into account the presence of many states, the application of the
inversion procedure produces very poor inference results. To overcome this
problem, we use the clustering algorithm. When the system has two symmetric
states of positive and negative magnetizations, the parameter reconstruction can
also be obtained with smaller computational effort simply by flipping the sign of
the magnetizations from positive to negative (or vice versa). The parameter
reconstruction fails when the system undergoes a phase transition: In that case
we give the correct inversion formulas for the Curie-Weiss model and we show that
they can be used to measure how close the system gets to being critical.
PMID- 29347522
TI - Semiclassical catastrophe theory of simple bifurcations.
AB - The Fedoriuk-Maslov catastrophe theory of caustics and turning points is extended
to solve the bifurcation problems by the improved stationary phase method (ISPM).
The trace formulas for the radial power-law (RPL) potentials are presented by the
ISPM based on the second- and third-order expansion of the classical action near
the stationary point. A considerable enhancement of contributions of the two
orbits (pair consisting of the parent and newborn orbits) at their bifurcation is
shown. The ISPM trace formula is proposed for a simple bifurcation scenario of
Hamiltonian systems with continuous symmetries, where the contributions of the
bifurcating parent orbits vanish upon approaching the bifurcation point due to
the reduction of the end-point manifold. This occurs since the contribution of
the parent orbits is included in the term corresponding to the family of the
newborn daughter orbits. Taking this feature into account, the ISPM level
densities calculated for the RPL potential model are shown to be in good
agreement with the quantum results at the bifurcations and asymptotically far
from the bifurcation points.
PMID- 29347523
TI - Microstructure and mechanical properties of hyperuniform heterogeneous materials.
AB - A hyperuniform random heterogeneous material is one in which the local volume
fraction fluctuations in an observation window decay faster than the reciprocal
window volume as the window size increases. Recent studies show that this class
of materials are endowed with superior physical properties such as large
isotropic photonic band gaps and optimal transport properties. Here we employ a
stochastic optimization procedure to systematically generate realizations of
hyperuniform heterogeneous materials with controllable short-range order, which
is partially quantified using the two-point correlation function S_{2}(r)
associated with the phase of interest. Specifically, our procedure generalizes
the widely used Yeong-Torquato reconstruction procedure by including an
additional constraint for hyperuniformity, i.e., the volume integral of the
autocovariance function chi(r)=S_{2}(r)-phi^{2} over the whole space is zero. In
addition, we only require the reconstructed S_{2} to match the target function up
to a certain cutoff distance gamma, in order to give the system sufficient
degrees of freedom to satisfy the hyperuniform condition. By systematically
increasing the gamma value for a given S_{2}, one can produce a spectrum of
hyperuniform heterogeneous materials with varying degrees of partial short-range
order compatible with the specified S_{2}. The mechanical performance including
both elastic and brittle fracture behaviors of the generated hyperuniform
materials is analyzed using a volume-compensated lattice-particle method. For the
purpose of comparison, the corresponding nonhyperuniform materials with the same
short-range order (i.e., with S_{2} constrained up to the same gamma value) are
also constructed and their mechanical performance is analyzed. Here we consider
two specific S_{2} including the positive exponential decay function and the
correlation function associated with an equilibrium hard-sphere system. For the
constructed systems associated with these two specific functions, we find that
although the hyperuniform materials are softer than their nonhyperuniform
counterparts, the former generally possess a significantly higher brittle
fracture strength than the latter. This superior mechanical behavior is
attributed to the lower degree of stress concentration in the material resulting
from the hyperuniform microstructure, which is crucial to crack initiation and
propagation.
PMID- 29347524
TI - Effect of high-order dispersion on three-soliton interactions for the variable
coefficients Hirota equation.
AB - The interactions of multiple solitons show different properties with two-soliton
interactions. For the difficulty of deriving multiple soliton solutions, it is
rare to study multiple soliton interactions analytically. In this paper, three
soliton interactions in inhomogeneous optical fibers, which are described by the
variable coefficient Hirota equation, are investigated. Via the Hirota bilinear
method and symbolic computation, analytic three-soliton solutions are obtained.
According to the obtained solutions, properties and features of three-soliton
interactions are discussed by changing the third-order dispersion (TOD) and other
relevant coefficients, and some plentiful structure of three-soliton interactions
are presented for the first time. The influences of TOD on the intensity and
propagation distance of solitons are described, which can be used to realize the
soliton control. Besides, the method that can achieve the phase reverse of
solitons is suggested, and bound states of three solitons are observed, which
have potential applications in the mode-locked fiber lasers. Furthermore,
comparing to two-soliton interactions, a novel phenomenon of three-soliton
interactions with a strong phase shift at x=0 is revealed, which is potentially
useful for optical logic switches.
PMID- 29347525
TI - Network patterns in exponentially growing two-dimensional biofilms.
AB - Anisotropic collective patterns occur frequently in the morphogenesis of two
dimensional biofilms. These patterns are often attributed to growth regulation
mechanisms and differentiation based on gradients of diffusing nutrients and
signaling molecules. Here, we employ a model of bacterial growth dynamics to show
that even in the absence of growth regulation or differentiation, confinement by
an enclosing medium such as agar can itself lead to stable pattern formation over
time scales that are employed in experiments. The underlying mechanism relies on
path formation through physical deformation of the enclosing environment.
PMID- 29347526
TI - Limit regimes of ice formation in turbulent supercooled water.
AB - A study of ice formation in stationary turbulent conditions is carried out in
various limit regimes of crystal growth, supercooling, and ice entrainment at the
water surface. Analytical expressions for the temperature, salinity, and ice
concentration mean profiles are provided, and the role of fluctuations in ice
production is numerically quantified. Lower bounds on the ratio of sensible heat
flux to latent heat flux to the atmosphere are derived and their dependence on
key parameters such as salt rejection in freezing and ice entrainment in the
water column is elucidated.
PMID- 29347527
TI - Collisional damping rates for electron plasma waves reassessed.
AB - Collisional damping of electron plasma waves, the primary damping for high phase
velocity waves, is proportional to the electron-ion collision rate, nu_{ei,th}.
Here, it is shown that the damping rate normalized to nu_{ei,th} depends on the
charge state, Z, on the magnitude of nu_{ei,th} and the wave number k in contrast
with the commonly used damping rate in plasma wave research. Only for weak
collision rates in low-Z plasmas for which the electron self-collision rate is
comparable to the electron-ion collision rate is the damping rate given by the
commonly accepted value. The result presented here corrects the result presented
in textbooks at least as early as 1973. The complete linear theory requires the
inclusion of both electron-ion pitch-angle and electron-electron scattering,
which itself contains contributions to both pitch-angle scattering and
thermalization.
PMID- 29347528
TI - Quantum work fluctuations in connection with the Jarzynski equality.
AB - A result of great theoretical and experimental interest, the Jarzynski equality
predicts a free energy change DeltaF of a system at inverse temperature beta from
an ensemble average of nonequilibrium exponential work, i.e., =e^{
betaDeltaF}. The number of experimental work values needed to reach a given
accuracy of DeltaF is determined by the variance of e^{-betaW}, denoted var(e^{
betaW}). We discover in this work that var(e^{-betaW}) in both harmonic and
anharmonic Hamiltonian systems can systematically diverge in nonadiabatic work
protocols, even when the adiabatic protocols do not suffer from such divergence.
This divergence may be regarded as a type of dynamically induced phase transition
in work fluctuations. For a quantum harmonic oscillator with time-dependent
trapping frequency as a working example, any nonadiabatic work protocol is found
to yield a diverging var(e^{-betaW}) at sufficiently low temperatures, markedly
different from the classical behavior. The divergence of var(e^{-betaW})
indicates the too-far-from-equilibrium nature of a nonadiabatic work protocol and
makes it compulsory to apply designed control fields to suppress the quantum work
fluctuations in order to test the Jarzynski equality.
PMID- 29347529
TI - Percolation thresholds in hyperbolic lattices.
AB - We use invasion percolation to compute numerical values for bond and site
percolation thresholds p_{c} (existence of an infinite cluster) and p_{u}
(uniqueness of the infinite cluster) of tesselations {P,Q} of the hyperbolic
plane, where Q faces meet at each vertex and each face is a P-gon. Our values are
accurate to six or seven decimal places, allowing us to explore their functional
dependency on P and Q and to numerically compute critical exponents. We also
prove rigorous upper and lower bounds for p_{c} and p_{u} that can be used to
find the scaling of both thresholds as a function of P and Q.
PMID- 29347530
TI - Stochastic efficiency of an isothermal work-to-work converter engine.
AB - We investigate the efficiency of an isothermal Brownian work-to-work converter
engine, composed of a Brownian particle coupled to a heat bath at a constant
temperature. The system is maintained out of equilibrium by using two external
time-dependent stochastic Gaussian forces, where one is called load force and the
other is called drive force. Work done by these two forces are stochastic
quantities. The efficiency of this small engine is defined as the ratio of
stochastic work done against load force to stochastic work done by the drive
force. The probability density function as well as large deviation function of
the stochastic efficiency are studied analytically and verified by numerical
simulations.
PMID- 29347531
TI - Local-stability analysis of a low-dissipation heat engine working at maximum
power output.
AB - In this paper we address the stability of a low-dissipation (LD) heat engine (HE)
under maximum power conditions. The LD system dynamics are analyzed in terms of
the contact times between the engine and the external heat reservoirs, which
determine the amount of heat exchanged by the system. We study two different
scenarios that secure the existence of a single stable steady state. In these
scenarios, contact times dynamics are governed by restitutive forces that are
linear functions of either the heat amounts exchanged per cycle, or the
corresponding heat fluxes. In the first case, according to our results,
preferably locating the system irreversibility sources at the hot-reservoir
coupling improves the system stability and increases its efficiency. On the other
hand, reducing the thermal gradient increases the system efficiency but
deteriorates its stability properties, because the restitutive forces are
smaller. Additionally, it is possible to compare the relaxation times with the
total cycle time and obtain some constraints upon the system dynamics. In the
second case, where the restitutive forces are assumed to be linear functions of
the heat fluxes, we find that although the partial contact time presents a
locally stable stationary value, the total cycle time does not; instead, there
exists an infinite collection of steady values located in the neighborhood of the
fixed point, along a one-dimensional manifold. Finally, the role of dissipation
asymmetries on the efficiency, the stability, and the ratio of the total cycle
time to the relaxation time is emphasized.
PMID- 29347532
TI - Dual lattice functional renormalization group for the Berezinskii-Kosterlitz
Thouless transition: Irrelevance of amplitude and out-of-plane fluctuations.
AB - We develop a functional renormalization group (FRG) approach for the two
dimensional XY model by combining the lattice FRG proposed by Machado and Dupuis
[Phys. Rev. E 82, 041128 (2010)PLEEE81539-375510.1103/PhysRevE.82.041128] with a
duality transformation that explicitly introduces vortices via an integer-valued
field. We show that the hierarchy of FRG flow equations for the infinite set of
relevant and marginal couplings of the model can be reduced to the well-known
Kosterlitz-Thouless renormalization group equations for the renormalized
temperature and the vortex fugacity. Within our approach it is straightforward to
include weak amplitude as well as out-of-plane fluctuations of the spins, which
lead to additional interactions between the vortices that do not spoil the
Berezinskii-Kosterlitz-Thouless transition. This demonstrates that previous
failures to obtain a line of true fixed points within the FRG are a mathematical
artifact of insufficient truncation schemes.
PMID- 29347533
TI - Model of chromosomal loci dynamics in bacteria as fractional diffusion with
intermittent transport.
AB - The short-time dynamics of bacterial chromosomal loci is a mixture of
subdiffusive and active motion, in the form of rapid relocations with near
ballistic dynamics. While previous work has shown that such rapid motions are
ubiquitous, we still have little grasp on their physical nature, and no positive
model is available that describes them. Here, we propose a minimal theoretical
model for loci movements as a fractional Brownian motion subject to a constant
but intermittent driving force, and compare simulations and analytical
calculations to data from high-resolution dynamic tracking in E. coli. This
analysis yields the characteristic time scales for intermittency. Finally, we
discuss the possible shortcomings of this model, and show that an increase in the
effective local noise felt by the chromosome associates to the active
relocations.
PMID- 29347534
TI - Exponential bound in the quest for absolute zero.
AB - In most studies for the quantification of the third law of thermodynamics, the
minimum temperature which can be achieved with a long but finite-time process
scales as a negative power of the process duration. In this article, we use our
recent complete solution for the optimal control problem of the quantum
parametric oscillator to show that the minimum temperature which can be obtained
in this system scales exponentially with the available time. The present work is
expected to motivate further research in the active quest for absolute zero.
PMID- 29347535
TI - Publisher's Note: Spreading law of non-Newtonian power-law liquids on a spherical
substrate by an energy-balance approach [Phys. Rev. E 96, 012803 (2017)].
AB - This corrects the article DOI: 10.1103/PhysRevE.96.012803.
PMID- 29347536
TI - Force fluctuations on a wall in interaction with a granular lid-driven cavity
flow.
AB - The force fluctuations experienced by a boundary wall subjected to a lid-driven
cavity flow are investigated by means of numerical simulations based on the
discrete-element method. The time-averaged dynamics inside the cavity volume and
the resulting steady force on the wall are governed by the boundary macroscopic
inertial number, the latter being derived from the shearing velocity and the
confinement pressure imposed at the top. The force fluctuations are quantified
through measuring both the autocorrelation of force time series and the
distributions of grain-wall forces, at distinct spatial scales from particle
scale to wall scale. A key result is that the grain-wall force distributions are
entirely driven by the boundary macroscopic inertial number, whatever the spatial
scale considered. In particular, when the wall scale is considered, the
distributions are found to evolve from nearly exponential to nearly Gaussian
distributions by decreasing the macroscopic inertial number. The transition from
quasistatic to dense inertial flow is well identified through remarkable changes
in the shapes of the distributions of grain-wall forces, accompanied by a loss of
system memory in terms of the mesoscale force transmitted toward the wall.
PMID- 29347537
TI - Ordering kinetics in the random-bond XY model.
AB - We present a comprehensive Monte Carlo study of domain growth in the random-bond
XY model with nonconserved kinetics. The presence of quenched disorder slows down
domain growth in d=2,3. In d=2, we observe power-law growth with a disorder
dependent exponent on the time scales of our simulation. In d=3, we see the
signature of an asymptotically logarithmic growth regime. The scaling functions
for the real-space correlation function are seen to be independent of the
disorder. However, the same does not apply for the two-time autocorrelation
function, demonstrating the breakdown of superuniversality.
PMID- 29347538
TI - Refined energy-conserving dissipative particle dynamics model with temperature
dependent properties and its application in solidification problem.
AB - It has been observed previously that the physical behaviors of Schmidt number
(Sc) and Prandtl number (Pr) of an energy-conserving dissipative particle
dynamics (eDPD) fluid can be reproduced by the temperature-dependent weight
function appearing in the dissipative force term. In this paper, we proposed a
simple and systematic method to develop the temperature-dependent weight function
in order to better reproduce the physical fluid properties. The method was then
used to study a variety of phase-change problems involving solidification. The
concept of the "mushy" eDPD particle was introduced in order to better capture
the temperature profile in the vicinity of the solid-liquid interface,
particularly for the case involving high thermal conductivity ratio. Meanwhile, a
way to implement the constant temperature boundary condition at the wall was
presented. The numerical solutions of one- and two-dimensional solidification
problems were then compared with the analytical solutions and/or experimental
results and the agreements were promising.
PMID- 29347539
TI - Theory of nanobubble formation and induced force in nanochannels.
AB - This paper presents a fundamental theory of nanobubble formation and induced
force in confined nanochannels. It is shown that nanobubble formation between
hydrophobic plates can be predicted from their surface tension and geometry, with
estimated values for the surface free energy and the force acting on the plates
in good agreement with the results of molecular dynamics simulation and
experimentation. When a bubble is formed between two plates, vertical attractive
force and horizontal retract force due to the shifted plates are applied to the
plates. The net force exerted on the plates is not dependent on the distance
between them. The short-range force between hydrophobic surfaces due to
hydrophobic interaction appears to correspond to the force estimated by our
theory. We compared between experimental and theoretical values for the binding
energy of a molecular motor system to validate our theory. The tendency that the
binding energy increases as the size of the protein increases is consistent with
the theory.
PMID- 29347540
TI - Compliant contact versus rigid contact: A comparison in the context of granular
dynamics.
AB - We summarize and numerically compare two approaches for modeling and simulating
the dynamics of dry granular matter. The first one, the discrete-element method
via penalty (DEM-P), is commonly used in the soft matter physics and geomechanics
communities; it can be traced back to the work of Cundall and Strack [P. Cundall,
Proc. Symp. ISRM, Nancy, France 1, 129 (1971); P. Cundall and O. Strack,
Geotechnique 29, 47 (1979)GTNQA80016-850510.1680/geot.1979.29.1.47]. The second
approach, the discrete-element method via complementarity (DEM-C), considers the
grains perfectly rigid and enforces nonpenetration via complementarity
conditions; it is commonly used in robotics and computer graphics applications
and had two strong promoters in Moreau and Jean [J. J. Moreau, in Nonsmooth
Mechanics and Applications, edited by J. J. Moreau and P. D. Panagiotopoulos
(Springer, Berlin, 1988), pp. 1-82; J. J. Moreau and M. Jean, Proceedings of the
Third Biennial Joint Conference on Engineering Systems and Analysis, Montpellier,
France, 1996, pp. 201-208]. The DEM-P and DEM-C are manifestly unlike each other:
They use different (i) approaches to model the frictional contact problem, (ii)
sets of model parameters to capture the physics of interest, and (iii) classes of
numerical methods to solve the differential equations that govern the dynamics of
the granular material. Herein, we report numerical results for five experiments:
shock wave propagation, cone penetration, direct shear, triaxial loading, and
hopper flow, which we use to compare the DEM-P and DEM-C solutions. This exercise
helps us reach two conclusions. First, both the DEM-P and DEM-C are predictive,
i.e., they predict well the macroscale emergent behavior by capturing the
dynamics at the microscale. Second, there are classes of problems for which one
of the methods has an advantage. Unlike the DEM-P, the DEM-C cannot capture shock
wave propagation through granular media. However, the DEM-C is proficient at
handling arbitrary grain geometries and solves, at large integration step sizes,
smaller problems, i.e., containing thousands of elements, very effectively. The
DEM-P vs DEM-C comparison is carried out using a public-domain, open-source
software package; the models used are available online.
PMID- 29347541
TI - Solid ^{4}He and the diffusion Monte Carlo method: A study of their properties.
AB - Properties of helium atoms in the solid phase are investigated using the
multiweight diffusion Monte Carlo method. Two different importance function
transformations are used in two series of independent calculations. The kinetic
energy is estimated for both the solid and liquid phases of ^{4}He. We estimate
the melting and freezing densities, among other properties of interest. Our
estimates are compared with experimental values. We discuss why walkers biased by
two distinctly different guiding functions do not lead to noticeable changes in
the reported results. Criticisms concerning the bias introduced into our
estimates by population control and system size effects are considered.
PMID- 29347542
TI - Breather solutions of a fourth-order nonlinear Schrodinger equation in the
degenerate, soliton, and rogue wave limits.
AB - We present one- and two-breather solutions of the fourth-order nonlinear
Schrodinger equation. With several parameters to play with, the solution may take
a variety of forms. We consider most of these cases including the general form
and limiting cases when the modulation frequencies are 0 or coincide. The zero
frequency limit produces a combination of breather-soliton structures on a
constant background. The case of equal modulation frequencies produces a
degenerate solution that requires a special technique for deriving. A zero
frequency limit of this degenerate solution produces a rational second-order
rogue wave solution with a stretching factor involved. Taking, in addition, the
zero limit of the stretching factor transforms the second-order rogue waves into
a soliton. Adding a differential shift in the degenerate solution results in
structural changes in the wave profile. Moreover, the zero-frequency limit of the
degenerate solution with differential shift results in a rogue wave triplet. The
zero limit of the stretching factor in this solution, in turn, transforms the
triplet into a singlet plus a low-amplitude soliton on the background. A large
value of the differential shift parameter converts the triplet into a pure
singlet.
PMID- 29347543
TI - Cover time for random walks on arbitrary complex networks.
AB - We present an analytical method for computing the mean cover time of a discrete
time random walk process on arbitrary, complex networks. The cover time is
defined as the time a random walker requires to visit every node in the network
at least once. This quantity is particularly important for random search
processes and target localization on network structures. Based on the global mean
first-passage time of target nodes, we derive a method for computing the
cumulative distribution function of the cover time based on first-passage time
statistics. Our method is viable for networks on which random walks equilibrate
quickly. We show that it can be applied successfully to various model and real
world networks. Our results reveal an intimate link between first-passage and
cover time statistics and offer a computationally efficient way for estimating
cover times in network-related applications.
PMID- 29347544
TI - Adiabatic elimination of inertia of the stochastic microswimmer driven by alpha
stable noise.
AB - We consider a microswimmer that moves in two dimensions at a constant speed and
changes the direction of its motion due to a torque consisting of a constant and
a fluctuating component. The latter will be modeled by a symmetric Levy-stable
(alpha-stable) noise. The purpose is to develop a kinetic approach to eliminate
the angular component of the dynamics to find a coarse-grained description in the
coordinate space. By defining the joint probability density function of the
position and of the orientation of the particle through the Fokker-Planck
equation, we derive transport equations for the position-dependent marginal
density, the particle's mean velocity, and the velocity's variance. At time
scales larger than the relaxation time of the torque tau_{phi}, the two higher
moments follow the marginal density and can be adiabatically eliminated. As a
result, a closed equation for the marginal density follows. This equation, which
gives a coarse-grained description of the microswimmer's positions at time scales
t?tau_{phi}, is a diffusion equation with a constant diffusion coefficient
depending on the properties of the noise. Hence, the long-time dynamics of a
microswimmer can be described as a normal, diffusive, Brownian motion with
Gaussian increments.
PMID- 29347545
TI - Erratum: Bypass rewiring and robustness of complex networks [Phys. Rev. E 94,
022310 (2016)].
AB - This corrects the article DOI: 10.1103/PhysRevE.94.022310.
PMID- 29347546
TI - Phase transitions in systems with aggregation and shattering.
AB - We consider a system of clusters made of elementary building blocks, monomers,
and evolving via collisions between diffusing monomers and immobile composite
clusters. In our model, the cluster-monomer collision can lead to the attachment
of the monomer to the cluster (addition process) or to the total breakup of the
cluster (shattering process). A phase transition, separating qualitatively
different behaviors, occurs when the probability of shattering events exceeds a
certain threshold. The novel feature of the phase transition is the dramatic
dependence on the initial conditions.
PMID- 29347547
TI - Observations of cavity polaritons in one-dimensional photonic crystals containing
a liquid-crystalline semiconductor based on perylene bisimide units.
AB - We investigated the optical transmission properties of one-dimensional photonic
crystal (1D-PC) microcavity structures containing the liquid-crystalline (LC)
perylene tetracarboxylic bisimide (PTCBI) derivative. We fabricated the
microcavity structures for this study by two different methods and observed the
cavity polaritons successfully in both samples. For one sample, since the PTCBI
molecules were aligned in the cavity layer of the 1D-PC by utilizing a friction
transfer method, vacuum Rabi splitting energy was strongly dependent on the
polarization of the incident light produced by the peculiar optical features of
the LC organic semiconductor. For the other sample, we did not utilize the
friction transfer method and did not observe such polarization dependence.
However, we did observe a relatively large Rabi splitting energy of 187 meV,
probably due to the improvement of optical confinement effect.
PMID- 29347548
TI - Temperature dependence of the Landau-Placzek ratio in liquid water.
AB - Rayleigh-Brillouin light scattering is studied in liquid water over the range
from 249 to 365 K. Experiments are carried out with a high spectral resolution
(0.1 GHz), eliminating any contribution of the structural relaxation to the
elastic line. The Landau-Placzek ratio is found as the ratio of the Rayleigh and
Brillouin intensities. In the whole temperature range, the Landau-Placzek ratio
is found to be in good agreement with a prediction of the theory with a pair of
independent thermodynamic variables, pressure and entropy. This description is
usually used for single-component homogeneous liquids. An excess of the Landau
Placzek ratio above the prediction is expected for inhomogeneous liquids and is
observed, for example, in glass-forming liquids below a certain temperature. In
contrast to glass-forming liquids, no excess of elastically scattered light
increasing at low temperatures is observed for the Landau-Placzek ratio of water.
This suggests that the Landau-Placzek ratio of liquid water can be described by a
homogeneous structure, and the idea of the water structure consisting of two
structural motifs may not be necessary to explain the experimental ratio.
PMID- 29347549
TI - Multiscale permutation entropy analysis of laser beam wandering in isotropic
turbulence.
AB - We have experimentally quantified the temporal structural diversity from the
coordinate fluctuations of a laser beam propagating through isotropic optical
turbulence. The main focus here is on the characterization of the long-range
correlations in the wandering of a thin Gaussian laser beam over a screen after
propagating through a turbulent medium. To fulfill this goal, a laboratory
controlled experiment was conducted in which coordinate fluctuations of the laser
beam were recorded at a sufficiently high sampling rate for a wide range of
turbulent conditions. Horizontal and vertical displacements of the laser beam
centroid were subsequently analyzed by implementing the symbolic technique based
on ordinal patterns to estimate the well-known permutation entropy. We show that
the permutation entropy estimations at multiple time scales evidence an interplay
between different dynamical behaviors. More specifically, a crossover between two
different scaling regimes is observed. We confirm a transition from an integrated
stochastic process contaminated with electronic noise to a fractional Brownian
motion with a Hurst exponent H=5/6 as the sampling time increases. Besides, we
are able to quantify, from the estimated entropy, the amount of electronic noise
as a function of the turbulence strength. We have also demonstrated that these
experimental observations are in very good agreement with numerical simulations
of noisy fractional Brownian motions with a well-defined crossover between two
different scaling regimes.
PMID- 29347550
TI - Stochastic maps, continuous approximation, and stable distribution.
AB - A continuous approximation framework for general nonlinear stochastic as well as
deterministic discrete maps is developed. For the stochastic map with uncorelated
Gaussian noise, by successively applying the Ito lemma, we obtain a Langevin type
of equation. Specifically, we show how nonlinear maps give rise to a Langevin
description that involves multiplicative noise. The multiplicative nature of the
noise induces an additional effective force, not present in the absence of noise.
We further exploit the continuum description and provide an explicit formula for
the stable distribution of the stochastic map and conditions for its existence.
Our results are in good agreement with numerical simulations of several maps.
PMID- 29347551
TI - Tensile elasticity of semiflexible polymers with hinge defects.
AB - It has become clear in recent years that the simple uniform wormlike chain model
needs to be modified in order to account for more complex behavior which has been
observed experimentally in some important biopolymers. For example, the large
flexibility of short ds-DNA has been attributed to kink or hinge defects. In this
paper, we calculate analytically, within the weak bending approximation, the
force-extension relation of a wormlike chain with a permanent hinge defect along
its contour. The defect is characterized by its bending energy (which can be
zero, in the completely flexible case) and its position along the polymer
contour. Besides the bending rigidity of the chain, these are the only parameters
which describe our model. We show that a hinge defect causes a significant
increase in the differential tensile compliance of a prestressed chain. In the
small force limit, a hinge defect significantly increases the entropic
elasticity. Our results apply to any pair of semiflexible segments connected by a
hinge. As such, they may also be relevant to cytoskeletal filaments (F-actin,
microtubules), where one may treat the cross-link connecting two filaments as a
hinge defect.
PMID- 29347552
TI - Complete diagrammatics of the single-ring theorem.
AB - Using diagrammatic techniques, we provide explicit functional relations between
the cumulant generating functions for the biunitarily invariant ensembles in the
limit of large size of matrices. The formalism allows us to map two distinct
areas of free random variables: Hermitian positive definite operators and non
normal R-diagonal operators. We also rederive the Haagerup-Larsen theorem and
show how its recent extension to the eigenvector correlation function appears
naturally within this approach.
PMID- 29347553
TI - Instabilities of convection patterns in a shear-thinning fluid between plates of
finite conductivity.
AB - Rayleigh-Benard convection in a horizontal layer of a non-Newtonian fluid between
slabs of arbitrary thickness and finite thermal conductivity is considered. The
first part of the paper deals with the primary bifurcation and the relative
stability of convective patterns at threshold. Weakly nonlinear analysis combined
with Stuart-Landau equation is used. The competition between squares and rolls,
as a function of the shear-thinning degree of the fluid, the slabs' thickness,
and the ratio of the thermal conductivity of the slabs to that of the fluid is
investigated. Computations of heat transfer coefficients are in agreement with
the maximum heat transfer principle. The second part of the paper concerns the
stability of the convective patterns toward spatial perturbations and the
determination of the band width of the stable wave number in the neighborhood of
the critical Rayleigh number. The approach used is based on the Ginzburg-Landau
equations. The study of rolls stability shows that: (i) for low shear-thinning
effects, the band of stable wave numbers is bounded by zigzag instability and
cross-roll instability. Furthermore, the marginal cross-roll stability boundary
enlarges with increasing shear-thinning properties; (ii) for high shear-thinning
effects, Eckhaus instability becomes more dangerous than cross-roll instability.
For square patterns, the wave number selection is always restricted by zigzag
instability and by "rectangular Eckhaus" instability. In addition, the width of
the stable wave number decreases with increasing shear-thinning effects.
Numerical simulations of the planform evolution are also presented to illustrate
the different instabilities considered in the paper.
PMID- 29347554
TI - Action at a distance in classical uniaxial ferromagnetic arrays.
AB - We examine in detail the theoretical foundations of striking long-range couplings
emerging in arrays of fluid cells connected by narrow channels by using a lattice
gas (Ising model) description of a system. We present a reexamination of the well
known exact determination of the two-point correlation function along the edge of
a channel using the transfer matrix technique and a different interpretation is
provided. The explicit form of the correlation length is found to grow
exponentially with the cross section of the channels at the bulk two-phase
coexistence. The aforementioned result is recaptured by a refined version of the
Fisher-Privman theory of first order phase transitions in which the Boltzmann
factor for a domain wall is decorated with a contribution stemming from the point
tension originated at its end points. The Boltzmann factor for a domain wall
together with the point tension is then identified exactly thanks to two
independent analytical techniques, providing a critical test of the Fisher
Privman theory. We then illustrate how to build up the network model from its
elementary constituents, the cells and the channels. Moreover, we are able to
extract the strength of the coupling between cells and express them in terms of
the length and width and coarse-grained quantities such as surface and point
tensions. We then support our theoretical investigation with a series of
corroborating results based on Monte Carlo simulations. We illustrate how the
long-range ordering occurs and how the latter is signaled by the thermodynamic
quantities corresponding to both planar and three-dimensional Ising arrays.
PMID- 29347555
TI - Morphing continuum theory for turbulence: Theory, computation, and visualization.
AB - A high order morphing continuum theory (MCT) is introduced to model highly
compressible turbulence. The theory is formulated under the rigorous framework of
rational continuum mechanics. A set of linear constitutive equations and balance
laws are deduced and presented from the Coleman-Noll procedure and Onsager's
reciprocal relations. The governing equations are then arranged in conservation
form and solved through the finite volume method with a second-order Lax
Friedrichs scheme for shock preservation. A numerical example of transonic flow
over a three-dimensional bump is presented using MCT and the finite volume
method. The comparison shows that MCT-based direct numerical simulation (DNS)
provides a better prediction than Navier-Stokes (NS)-based DNS with less than 10%
of the mesh number when compared with experiments. A MCT-based and frame
indifferent Q criterion is also derived to show the coherent eddy structure of
the downstream turbulence in the numerical example. It should be emphasized that
unlike the NS-based Q criterion, the MCT-based Q criterion is objective without
the limitation of Galilean invariance.
PMID- 29347556
TI - One-dimensional description of driven diffusion in periodic channels.
AB - Diffusion of point-like particles driven by a constant longitudinal force in two
dimensional channels of periodically varying width is studied. The dynamics of
such systems can be effectively described by the one-dimensional Smoluchowski(
Fick-Jacobs) equation in the longitudinal coordinate x, extended by a space
dependent effective diffusion coefficient D(x). Our paper is focused on
calculation of this function for an arbitrary channel shaping function h(x).
Unlike the previous algorithms based on scaling of the transverse lengths, the
method presented here uses periodicity of the channel. Instead of complicated
expansion containing higher order derivatives of h(x), the proposed algorithm
results in an integral formula for D(x), enabling us to study the system for wide
range of the driving force and various (periodic) shaping functions h(x).
PMID- 29347557
TI - Constant-pressure nested sampling with atomistic dynamics.
AB - The nested sampling algorithm has been shown to be a general method for
calculating the pressure-temperature-composition phase diagrams of materials.
While the previous implementation used single-particle Monte Carlo moves, these
are inefficient for condensed systems with general interactions where single
particle moves cannot be evaluated faster than the energy of the whole system.
Here we enhance the method by using all-particle moves: either Galilean Monte
Carlo or the total enthalpy Hamiltonian Monte Carlo algorithm, introduced in this
paper. We show that these algorithms enable the determination of phase transition
temperatures with equivalent accuracy to the previous method at 1/N of the cost
for an N-particle system with general interactions, or at equal cost when single
particle moves can be done in 1/N of the cost of a full N-particle energy
evaluation. We demonstrate this speed-up for the freezing and condensation
transitions of the Lennard-Jones system and show the utility of the algorithms by
calculating the order-disorder phase transition of a binary Lennard-Jones model
alloy, the eutectic of copper-gold, the density anomaly of water, and the
condensation and solidification of bead-spring polymers. The nested sampling
method with all three algorithms is implemented in the pymatnest software.
PMID- 29347558
TI - Complete delocalization in a defective periodic structure.
AB - We report on the existence of stable, completely delocalized response regimes in
a nonlinear defective periodic structure. In this state of complete
delocalization, despite the presence of the defect, the system exhibits in-phase
oscillation of all units with the same amplitude. This elimination of defect
borne localization may occur in both the free and forced responses of the system.
In the absence of external driving, the localized defect mode becomes completely
delocalized at a certain energy level. In the case of a damped-driven system,
complete delocalization may be realized if the driving amplitude is beyond a
certain threshold. We demonstrate this phenomenon numerically in a linear
periodic structure with one and two defective units possessing a nonlinear
restoring force. We derive closed-form analytical expressions for the onset of
complete delocalization, and we discuss the necessary conditions for its
occurrence.
PMID- 29347559
TI - How anisotropy beats fractality in two-dimensional on-lattice diffusion-limited
aggregation growth.
AB - We study the fractal structure of diffusion-limited aggregation (DLA) clusters on
a square lattice by extensive numerical simulations (with clusters having up to
10^{8} particles). We observe that DLA clusters undergo strongly anisotropic
growth, with the maximal growth rate along the axes. The naive scaling limit of a
DLA cluster by its diameter is thus deterministic and one-dimensional. At the
same time, on all scales from the particle size to the size of the entire cluster
it has a nontrivial box-counting fractal dimension which corresponds to the
overall growth rate, which, in turn, is smaller than the growth rate along the
axes. This suggests that the fractal nature of the lattice DLA should be
understood in terms of fluctuations around the one-dimensional backbone of the
cluster.
PMID- 29347560
TI - Effect of capillary condensation on gas transport properties in porous media.
AB - We investigate the effect of capillary condensation on gas diffusivity in porous
media composed of randomly packed spheres with moderate wettability. To simulate
capillary phenomena at the pore scale while retaining complex pore networks of
the porous media, we employ density functional theory (DFT) for coarse-grained
lattice gas models. The lattice DFT simulations reveal that capillary
condensations preferentially occur at confined pores surrounded by solid walls,
leading to the occlusion of narrow pores. Consequently, the characteristic
lengths of the partially wet structures are larger than those of the
corresponding dry structures with the same porosities. Subsequent gas diffusion
simulations exploiting the mean-square displacement method indicate that while
the effective diffusion coefficients significantly decrease in the presence of
partially condensed liquids, they are larger than those in the dry structures
with the same porosities. Moreover, we find that the ratio of the porosity to the
tortuosity factor, which is a crucial parameter that determines an effective
diffusion coefficient, can be reasonably related to the porosity even for the
partially wet porous media.
PMID- 29347561
TI - Irreversible thermodynamics of curved lipid membranes.
AB - The theory of irreversible thermodynamics for arbitrarily curved lipid membranes
is presented here. The coupling between elastic bending and irreversible
processes such as intramembrane lipid flow, intramembrane phase transitions, and
protein binding and diffusion is studied. The forms of the entropy production for
the irreversible processes are obtained, and the corresponding thermodynamic
forces and fluxes are identified. Employing the linear irreversible thermodynamic
framework, the governing equations of motion along with appropriate boundary
conditions are provided.
PMID- 29347562
TI - Rational extended thermodynamics of a rarefied polyatomic gas with molecular
relaxation processes.
AB - We present a more refined version of rational extended thermodynamics of rarefied
polyatomic gases in which molecular rotational and vibrational relaxation
processes are treated individually. In this case, we need a triple hierarchy of
the moment system and the system of balance equations is closed via the maximum
entropy principle. Three different types of the production terms in the system,
which are suggested by a generalized BGK-type collision term in the Boltzmann
equation, are adopted. In particular, the rational extended thermodynamic theory
with seven independent fields (ET_{7}) is analyzed in detail. Finally, the
dispersion relation of ultrasonic wave derived from the ET_{7} theory is
confirmed by the experimental data for CO_{2}, Cl_{2}, and Br_{2} gases.
PMID- 29347563
TI - Importance of small-degree nodes in assortative networks with degree-weight
correlations.
AB - It has been known that assortative network structure plays an important role in
spreading dynamics for unweighted networks. Yet its influence on weighted
networks is not clear, in particular when weight is strongly correlated with the
degrees of the nodes as we empirically observed in Twitter. Here we use the self
consistent probability method and revised nonperturbative heterogenous mean-field
theory method to investigate this influence on both susceptible-infective
recovered (SIR) and susceptible-infective-susceptible (SIS) spreading dynamics.
Both our simulation and theoretical results show that while the critical
threshold is not significantly influenced by the assortativity, the prevalence in
the supercritical regime shows a crossover under different degree-weight
correlations. In particular, unlike the case of random mixing networks, in
assortative networks, the negative degree-weight correlation leads to higher
prevalence in their spreading beyond the critical transmissivity than that of the
positively correlated. In addition, the previously observed inhibition effect on
spreading velocity by assortative structure is not apparent in negatively degree
weight correlated networks, while it is enhanced for that of the positively
correlated. Detailed investigation into the degree distribution of the infected
nodes reveals that small-degree nodes play essential roles in the supercritical
phase of both SIR and SIS spreadings. Our results have direct implications in
understanding viral information spreading over online social networks and
epidemic spreading over contact networks.
PMID- 29347564
TI - Epidemic spreading on activity-driven networks with attractiveness.
AB - We study SIS epidemic spreading processes unfolding on a recent generalization of
the activity-driven modeling framework. In this model of time-varying networks,
each node is described by two variables: activity and attractiveness. The first
describes the propensity to form connections, while the second defines the
propensity to attract them. We derive analytically the epidemic threshold
considering the time scale driving the evolution of contacts and the contagion as
comparable. The solutions are general and hold for any joint distribution of
activity and attractiveness. The theoretical picture is confirmed via large-scale
numerical simulations performed considering heterogeneous distributions and
different correlations between the two variables. We find that heterogeneous
distributions of attractiveness alter the contagion process. In particular, in
the case of uncorrelated and positive correlations between the two variables,
heterogeneous attractiveness facilitates the spreading. On the contrary, negative
correlations between activity and attractiveness hamper the spreading. The
results presented contribute to the understanding of the dynamical properties of
time-varying networks and their effects on contagion phenomena unfolding on their
fabric.
PMID- 29347565
TI - Formation and evolution of target patterns in Cahn-Hilliard flows.
AB - We study the evolution of the concentration field in a single eddy in the two
dimensional (2D) Cahn-Hilliard system to better understand scalar mixing
processes in that system. This study extends investigations of the classic
studies of flux expulsion in 2D magnetohydrodynamics and homogenization of
potential vorticity in 2D fluids. Simulation results show that there are three
stages in the evolution: (A) formation of a "jelly roll" pattern, for which the
concentration field is constant along spirals; (B) a change in isoconcentration
contour topology; and (C) formation of a target pattern, for which the
isoconcentration contours follow concentric annuli. In the final target pattern
stage, the isoconcentration bands align with stream lines. The results indicate
that the target pattern is a metastable state. The band merger process continues
on a time scale exponentially long relative to the eddy turnover time. The band
merger process resembles step merger in drift-ZF staircases; this is
characteristic of the long-time evolution of phase-separated patterns described
by the Cahn-Hilliard equation.
PMID- 29347566
TI - Macroscopic phase-resetting curves for spiking neural networks.
AB - The study of brain rhythms is an open-ended, and challenging, subject of interest
in neuroscience. One of the best tools for the understanding of oscillations at
the single neuron level is the phase-resetting curve (PRC). Synchronization in
networks of neurons, effects of noise on the rhythms, effects of transient
stimuli on the ongoing rhythmic activity, and many other features can be
understood by the PRC. However, most macroscopic brain rhythms are generated by
large populations of neurons, and so far it has been unclear how the PRC
formulation can be extended to these more common rhythms. In this paper, we
describe a framework to determine a macroscopic PRC (mPRC) for a network of
spiking excitatory and inhibitory neurons that generate a macroscopic rhythm. We
take advantage of a thermodynamic approach combined with a reduction method to
simplify the network description to a small number of ordinary differential
equations. From this simplified but exact reduction, we can compute the mPRC via
the standard adjoint method. Our theoretical findings are illustrated with and
supported by numerical simulations of the full spiking network. Notably our mPRC
framework allows us to predict the difference between effects of transient inputs
to the excitatory versus the inhibitory neurons in the network.
PMID- 29347567
TI - Kinetics of biochemical sensing by single cells and populations of cells.
AB - We investigate the collective stationary sensing using N communicative cells,
which involves surface receptors, diffusive signaling molecules, and cell-cell
communication messengers. We restrict the scenarios to the signal-to-noise ratios
(SNRs) for both strong communication and extrinsic noise only. We modified a
previous model [Bialek and Setayeshgar, Proc. Natl. Acad. Sci. USA 102, 10040
(2005)PNASA60027-842410.1073/pnas.0504321102] to eliminate the singularities in
the fluctuation correlations by considering a uniform receptor distribution over
the surface of each cell with a finite radius a. The modified model enables a
simple and rigorous mathematical treatment of the collective sensing phenomenon.
We then derive the scaling of the SNR for both juxtacrine and autocrine cases in
all dimensions. For the optimal locations of the cells in the autocrine case, we
find identical scaling for both two and three dimensions.
PMID- 29347568
TI - Impact of environmental colored noise in single-species population dynamics.
AB - Variability on external conditions has important consequences for the dynamics
and the organization of biological systems. In many cases, the characteristic
timescale of environmental changes as well as their correlations play a
fundamental role in the way living systems adapt and respond to it. A proper
mathematical approach to understand population dynamics, thus, requires
approaches more refined than, e.g., simple white-noise approximations. To shed
further light onto this problem, in this paper we propose a unifying framework
based on different analytical and numerical tools available to deal with
"colored" environmental noise. In particular, we employ a "unified colored noise
approximation" to map the original problem into an effective one with white
noise, and then we apply a standard path integral approach to gain analytical
understanding. For the sake of specificity, we present our approach using as a
guideline a variation of the contact process-which can also be seen as a birth
death process of the Malthus-Verhulst class-where the propagation or birth rate
varies stochastically in time. Our approach allows us to tackle in a systematic
manner some of the relevant questions concerning population dynamics under
environmental variability, such as determining the stationary population density,
establishing the conditions under which a population may become extinct, and
estimating extinction times. We focus on the emerging phase diagram and its
possible phase transitions, underlying how these are affected by the presence of
environmental noise time-correlations.
PMID- 29347569
TI - Scaling of the surface vasculature on the human placenta.
AB - The networks of veins and arteries on the chorionic plate of the human placenta
are analyzed in terms of Voronoi cells derived from these networks. Two groups of
placentas from the United States are studied: a population cohort with no
prescreening, and a cohort from newborns with an elevated risk of developing
autistic spectrum disorder. Scaled distributions of the Voronoi cell areas in the
two cohorts collapse onto a single distribution, indicating common mechanisms for
the formation of the complete vasculatures, but which have different levels of
activity in the two cohorts.
PMID- 29347570
TI - Flame propagation in two-dimensional solids: Particle-resolved studies with
complex plasmas.
AB - Using two-dimensional (2D) complex plasmas as an experimental model system,
particle-resolved studies of flame propagation in classical 2D solids are carried
out. Combining experiments, theory, and molecular dynamics simulations, we
demonstrate that the mode-coupling instability operating in 2D complex plasmas
reveals all essential features of combustion, such as an activated heat release,
two-zone structure of the self-similar temperature profile ("flame front"), as
well as thermal expansion of the medium and temperature saturation behind the
front. The presented results are of relevance for various fields ranging from
combustion and thermochemistry, to chemical physics and synthesis of materials.
PMID- 29347571
TI - Diffusion dynamics and synchronizability of hierarchical products of networks.
AB - The hierarchical product of networks represents a natural tool for building large
networks out of two smaller subnetworks: a primary subnetwork and a secondary
subnetwork. Here we study the dynamics of diffusion and synchronization processes
on hierarchical products. We apply techniques previously used for approximating
the eigenvalues of the adjacency matrix to the Laplacian matrix, allowing us to
quantify the effects that the primary and secondary subnetworks have on diffusion
and synchronization in terms of a coupling parameter that weighs the secondary
subnetwork relative to the primary subnetwork. Diffusion processes are separated
into two regimes: for small coupling the diffusion rate is determined by the
structure of the secondary network, scaling with the coupling parameter, while
for large coupling it is determined by the primary network and saturates.
Synchronization, on the other hand, is separated into three regimes, for both
small and large coupling hierarchical products have poor synchronization
properties, but is optimized at an intermediate value. Moreover, the critical
coupling value that optimizes synchronization is shaped by the relative
connectivities of the primary and secondary subnetworks, compensating for
significant differences between the two subnetworks.
PMID- 29347572
TI - Multichain models of conserved lattice gas.
AB - Conserved lattice-gas models in one dimension exhibit absorbing state phase
transition (APT) with simple integer exponents beta=1=nu=eta, whereas the same on
a ladder belong to directed percolation (DP) universality. We conjecture that
additional stochasticity in particle transfer is a relevant perturbation and its
presence on a ladder forces the APT to be in the DP class. To substantiate this
we introduce a class of restricted conserved lattice-gas models on a multichain
system (M*L square lattice with periodic boundary condition in both directions),
where particles which have exactly one vacant neighbor are active and they move
deterministically to the neighboring vacant site. We show that for odd number of
chains, in the thermodynamic limit L->infinity, these models exhibit APT at
rho_{c}=1/2(1+1/M) with beta=1. On the other hand, for even-chain systems
transition occurs at rho_{c}=1/2 with beta=1,2 for M=2,4, respectively, and
beta=3 for M>=6. We illustrate this unusual critical behavior analytically using
a transfer-matrix method.
PMID- 29347573
TI - Tricriticality in crossed Ising chains.
AB - We explore the phase diagram of Ising spins on one-dimensional chains that criss
cross in two perpendicular directions and that are connected by interchain
couplings. This system is of interest as a simpler, classical analog of a quantum
Hamiltonian that has been proposed as a model of magnetic behavior in
Nb_{12}O_{29} and also, conceptually, as a geometry that is intermediate between
one and two dimensions. Using mean-field theory as well as Metropolis Monte Carlo
and Wang-Landau simulations, we locate quantitatively the boundaries of four
ordered phases. Each becomes an effective Ising model with unique effective
couplings at large interchain coupling. Away from this limit, we demonstrate
nontrivial critical behavior, including tricritical points that separate first-
and second-order phase transitions. Finally, we present evidence that this model
belongs to the two-dimensional Ising universality class.
PMID- 29347574
TI - Emergence of biaxial nematic phases in solutions of semiflexible dimers.
AB - We investigate the isotropic, uniaxial nematic and biaxial nematic phases, and
the transitions between them, for a model lyotropic mixture of flexible molecules
consisting of two rigid rods connected by a spacer with variable bending
stiffness. We apply density-functional theory within the Onsager approximation to
describe strictly excluded-volume interactions in this athermal model and to self
consistently find the orientational order parameters dictated by its complex
symmetry, as functions of the density. Earlier work on lyotropic ordering of
rigid bent-rod molecules is reproduced and extended to show explicitly the
continuous phase transition at the Landau point, at a critical bend angle of
36^{?}. For flexible dimers with no intrinsic biaxiality, we find that a biaxial
nematic phase can nevertheless form at a sufficiently high density and low
bending stiffness. For bending stiffness kappa>0.86k_{B}T, this biaxial phase
manifests as dimer bending fluctuations occurring preferentially in one plane.
When the dimers are more flexible, kappa<0.86k_{B}T, the modal shape of the
fluctuating dimer is a V with an acute opening angle, and one of the biaxial
order parameters changes sign, indicating a rotation of the directors. These two
regions are separated by a narrow strip of uniaxial nematic in the phase diagram,
which we generate in terms of the spacer stiffness and particle density.
PMID- 29347575
TI - Critical phenomena of a hybrid phase transition in cluster merging dynamics.
AB - Recently, a hybrid percolation transition (HPT) that exhibits both a
discontinuous transition and critical behavior at the same transition point has
been observed in diverse complex systems. While the HPT induced by avalanche
dynamics has been studied extensively, the HPT induced by cluster merging
dynamics (HPT-CMD) has received little attention. Here, we aim to develop a
theoretical framework for the HPT-CMD. We find that two correlation-length
exponents are necessary for characterizing the giant cluster and finite clusters
separately. The conventional formula of the fractal dimension in terms of the
critical exponents is not valid. Neither the giant nor finite clusters are
fractals, but they have fractal boundaries. A finite-size scaling method for the
HPT-CMD is also introduced.
PMID- 29347576
TI - Multiscale Granger causality.
AB - In the study of complex physical and biological systems represented by
multivariate stochastic processes, an issue of great relevance is the description
of the system dynamics spanning multiple temporal scales. While methods to assess
the dynamic complexity of individual processes at different time scales are well
established, multiscale analysis of directed interactions has never been
formalized theoretically, and empirical evaluations are complicated by practical
issues such as filtering and downsampling. Here we extend the very popular
measure of Granger causality (GC), a prominent tool for assessing directed lagged
interactions between joint processes, to quantify information transfer across
multiple time scales. We show that the multiscale processing of a vector
autoregressive (AR) process introduces a moving average (MA) component, and
describe how to represent the resulting ARMA process using state space (SS)
models and to combine the SS model parameters for computing exact GC values at
arbitrarily large time scales. We exploit the theoretical formulation to identify
peculiar features of multiscale GC in basic AR processes, and demonstrate with
numerical simulations the much larger estimation accuracy of the SS approach
compared to pure AR modeling of filtered and downsampled data. The improved
computational reliability is exploited to disclose meaningful multiscale patterns
of information transfer between global temperature and carbon dioxide
concentration time series, both in paleoclimate and in recent years.
PMID- 29347577
TI - Lognormal-like statistics of a stochastic squeeze process.
AB - We analyze the full statistics of a stochastic squeeze process. The model's two
parameters are the bare stretching rate w and the angular diffusion coefficient
D. We carry out an exact analysis to determine the drift and the diffusion
coefficient of log(r), where r is the radial coordinate. The results go beyond
the heuristic lognormal description that is implied by the central limit theorem.
Contrary to the common "quantum Zeno" approximation, the radial diffusion is not
simply D_{r}=(1/8)w^{2}/D but has a nonmonotonic dependence on w/D. Furthermore,
the calculation of the radial moments is dominated by the far non-Gaussian tails
of the log(r) distribution.
PMID- 29347578
TI - Turbulent flow over craters on Mars: Vorticity dynamics reveal aeolian excavation
mechanism.
AB - Impact craters are scattered across Mars. These craters exhibit geometric self
similarity over a spectrum of diameters, ranging from tens to thousands of
kilometers. The late Noachian-early Hesperian boundary marks a dramatic shift in
the role of mid-latitude craters, from depocenter sedimentary basins to aeolian
source areas. At present day, many craters contain prominent layered sedimentary
mounds with maximum elevations comparable to the rim height. The mounds are
remnants of Noachian deposition and are surrounded by a radial moat. Large-eddy
simulation has been used to model turbulent flows over synthetic craterlike
geometries. Geometric attributes of the craters and the aloft flow have been
carefully matched to resemble ambient conditions in the atmospheric boundary
layer of Mars. Vorticity dynamics analysis within the crater basin reveals the
presence of counterrotating helical vortices, verifying the efficacy of
deflationary models put forth recently by Bennett and Bell [K. Bennett and J.
Bell, Icarus 264, 331 (2016)]ICRSA50019-103510.1016/j.icarus.2015.09.041 and Day
et al. [M. Day et al., Geophys. Res. Lett. 43, 2473 (2016)]GPRLAJ0094
827610.1002/2016GL068011. We show how these helical counterrotating vortices
spiral around the outer rim, gradually deflating the moat and carving the mound;
excavation occurs faster on the upwind side, explaining the radial eccentricity
of the mounds relative to the surrounding crater basin.
PMID- 29347579
TI - Electrostatic fluctuations in collisional plasmas.
AB - We present a theory of electrostatic fluctuations in two-component plasmas where
electrons and ions are described by Maxwellian distribution functions at unequal
temperatures. Based on the exact solution of the Landau kinetic equation, that
includes electron-electron, electron-ion, and ion-ion collision integrals, the
dynamic form factor, S(k[over ?],omega), is derived for weakly coupled plasmas.
The collective plasma responses at ion-acoustic, Langmuir, and entropy mode
resonances are described for arbitrary wave numbers and frequencies in the entire
range of plasma collisionality. The collisionless limit of S(k[over ?],omega) and
the strong-collision result based on the fluctuation-dissipation theorem and
classical transport at T_{e}=T_{i} are recovered and discussed. Results of
several Thomson scattering experiments in the broad range of plasma parameters
are described and discussed by means of our theory for S(k[over ?],omega).
PMID- 29347580
TI - Kinetic approach to condensation: Diatomic gases with dipolar molecules.
AB - We derive a kinetic equation for rarefied diatomic gases whose molecules have a
permanent dipole moment. Estimating typical parameters of such gases, we show
that quantum effects cannot be neglected when describing the rotation of
molecules, which we thus approximate by quantum rotators. The intermolecular
potential is assumed to involve an unspecified short-range repulsive component
and a long-range dipole-dipole Coulomb interaction. In the kinetic equation
derived, the former and the latter give rise, respectively, to the collision
integral and a self-consistent electric field generated collectively by the
dipoles (as in the Vlasov model of plasma). It turns out that the characteristic
period of the molecules' rotation is much shorter than the time scale of the
collective electric force and the latter is much shorter than the time scale of
the collision integral, which allows us to average the kinetic equation over
rotation. In the averaged model, collisions and interaction with the collective
field affect only those rotational levels of the molecules that satisfy certain
conditions of synchronism. It is then shown that the derived model does not
describe condensation; i.e., permanent dipoles of molecules cannot exert the
level of intermolecular attraction necessary for condensation. It is argued that
an adequate model of condensation must include the temporary dipoles that
molecules induce on each other during interaction, and that this model must be
quantum, not classical.
PMID- 29347581
TI - Noisy independent component analysis of autocorrelated components.
AB - We present a method for the separation of superimposed, independent,
autocorrelated components from noisy multichannel measurement. The presented
method simultaneously reconstructs and separates the components, taking all
channels into account, and thereby increases the effective signal-to-noise ratio
considerably, allowing separations even in the high-noise regime. Characteristics
of the measurement instruments can be included, allowing for application in
complex measurement situations. Independent posterior samples can be provided,
permitting error estimates on all desired quantities. Using the concept of
information field theory, the algorithm is not restricted to any dimensionality
of the underlying space or discretization scheme thereof.
PMID- 29347582
TI - Estimation of the degree of dynamical instability from the information entropy of
symbolic dynamics.
AB - A positive Lyapunov exponent is the most convincing signature of chaos. However,
existing methods for estimating the Lyapunov exponent from a time series often
give unreliable estimates because they trace the time evolution of the distance
between a pair of initially neighboring trajectories in phase space. Here, we
propose a mathematical method for estimating the degree of dynamical instability,
as a surrogate for the Lyapunov exponent, without tracing initially neighboring
trajectories on the basis of the information entropy from a symbolic time series.
We apply the proposed method to numerical time series generated by well-known
chaotic systems and experimental time series and verify its validity.
PMID- 29347583
TI - Quantum Monte Carlo with variable spins: Fixed-phase and fixed-node
approximations.
AB - We study several aspects of the recently introduced fixed-phase spinor diffusion
Monte Carlo method, in particular, its relation to the fixed-node method and its
potential use as a general approach for electronic structure calculations. We
illustrate constructions of spinor-based wave functions with the full space-spin
symmetry without assigning up or down spin labels to particular electrons,
effectively "complexifying" even ordinary real-valued wave functions for
Hamiltonians without spin terms. Interestingly, with proper choice of the
simulation parameters and spin variables, such fixed-phase calculations enable
one to reach also the fixed-node limit. The fixed-phase approximation has several
desirable properties when compared to the fixed-node approximation. The fixed
phase solution provides a straightforward interpretation as the lowest bosonic
state in a given effective potential generated by the many-body approximate
phase, whereas nodal boundary conditions are defined through less intuitive and
complicated hypersurfaces with one dimension less than the original configuration
space. In addition, the divergences of the local energy and drift at real wave
function nodes are smoothed out to lower dimensionality when the wave function is
complexified, thus decreasing the variation of sampled quantities and eliminating
artificial nodal domain issues that can occur in the fixed-node formalism. We
illustrate some of these properties on calculations of selected first-row systems
that recover the fixed-node results with quantitatively similar levels of the
corresponding biases. At the same time, the fixed-phase approach opens new
possibilities for more general trial wave functions with further opportunities
for increasing accuracy in practical calculations.
PMID- 29347584
TI - Crossover from ballistic to normal heat transport in the phi^{4} lattice: If
nonconservation of momentum is the reason, what is the mechanism?
AB - Anomalous (non-Fourier) heat transport is no longer just a theoretical issue
since it has been observed experimentally in a number of low-dimensional
nanomaterials, such as SiGe nanowires, carbon nanotubes, and others. To
understand these anomalous behaviors, exploring the microscopic origin of normal
(Fourier) heat transport is a fascinating theoretical topic. However, this issue
has not yet been fully understood even for one-dimensional (1D) model chains, in
spite of a great amount of thorough studies done to date. From those studies, it
has been widely accepted that the conservation of momentum is a key ingredient to
induce anomalous heat transport, while momentum-nonconserving systems usually
support normal heat transport where Fourier's law is valid. But if the
nonconservation of momentum is the reason, what is the underlying microscopic
mechanism for the observed normal heat transport? Here we carefully revisit a
typical 1D momentum-nonconserving phi^{4} model, and we present evidence that the
mobile discrete breathers, or, in other words, the moving intrinsic localized
modes with frequency components above the linear phonon band, can be responsible
for that.
PMID- 29347585
TI - Reconstruction of a digital core containing clay minerals based on a clustering
algorithm.
AB - It is difficult to obtain a core sample and information for digital core
reconstruction of mature sandstone reservoirs around the world, especially for an
unconsolidated sandstone reservoir. Meanwhile, reconstruction and division of
clay minerals play a vital role in the reconstruction of the digital cores,
although the two-dimensional data-based reconstruction methods are specifically
applicable as the microstructure reservoir simulation methods for the sandstone
reservoir. However, reconstruction of clay minerals is still challenging from a
research viewpoint for the better reconstruction of various clay minerals in the
digital cores. In the present work, the content of clay minerals was considered
on the basis of two-dimensional information about the reservoir. After
application of the hybrid method, and compared with the model reconstructed by
the process-based method, the digital core containing clay clusters without the
labels of the clusters' number, size, and texture were the output. The statistics
and geometry of the reconstruction model were similar to the reference model. In
addition, the Hoshen-Kopelman algorithm was used to label various connected
unclassified clay clusters in the initial model and then the number and size of
clay clusters were recorded. At the same time, the K-means clustering algorithm
was applied to divide the labeled, large connecting clusters into smaller
clusters on the basis of difference in the clusters' characteristics. According
to the clay minerals' characteristics, such as types, textures, and
distributions, the digital core containing clay minerals was reconstructed by
means of the clustering algorithm and the clay clusters' structure judgment. The
distributions and textures of the clay minerals of the digital core were
reasonable. The clustering algorithm improved the digital core reconstruction and
provided an alternative method for the simulation of different clay minerals in
the digital cores.
PMID- 29347586
TI - Bak-Tang-Wiesenfeld model in the upper critical dimension: Induced criticality in
lower-dimensional subsystems.
AB - We present extensive numerical simulations of Bak-Tang-Wiesenfeld (BTW) sandpile
model on the hypercubic lattice in the upper critical dimension D_{u}=4. After re
extracting the critical exponents of avalanches, we concentrate on the three- and
two-dimensional (2D) cross sections seeking for the induced criticality which are
reflected in the geometrical and local exponents. Various features of finite-size
scaling (FSS) theory have been tested and confirmed for all dimensions. The
hyperscaling relations between the exponents of the distribution functions and
the fractal dimensions are shown to be valid for all dimensions. We found that
the exponent of the distribution function of avalanche mass is the same for the d
dimensional cross sections and the d-dimensional BTW model for d=2 and 3. The
geometrical quantities, however, have completely different behaviors with respect
to the same-dimensional BTW model. By analyzing the FSS theory for the
geometrical exponents of the two-dimensional cross sections, we propose that the
2D induced models have degrees of similarity with the Gaussian free field (GFF).
Although some local exponents are slightly different, this similarity is
excellent for the fractal dimensions. The most important one showing this feature
is the fractal dimension of loops d_{f}, which is found to be 1.50+/
0.02~3/2=d_{f}^{GFF}.
PMID- 29347587
TI - Spectral estimation of the percolation transition in clustered networks.
AB - There have been several spectral bounds for the percolation transition in
networks, using spectrum of matrices associated with the network such as the
adjacency matrix and the nonbacktracking matrix. However, they are far from being
tight when the network is sparse and displays clustering or transitivity, which
is represented by existence of short loops, e.g., triangles. In this paper, for
the bond percolation, we first propose a message-passing algorithm for
calculating size of percolating clusters considering effects of triangles, then
relate the percolation transition to the leading eigenvalue of a matrix that we
name the triangle-nonbacktracking matrix, by analyzing stability of the message
passing equations. We establish that our method gives a tighter lower bound to
the bond percolation transition than previous spectral bounds, and it becomes
exact for an infinite network with no loops longer than 3. We evaluate
numerically our methods on synthetic and real-world networks, and discuss further
generalizations of our approach to include higher-order substructures.
PMID- 29347588
TI - Finite-size effects in canonical and grand-canonical quantum Monte Carlo
simulations for fermions.
AB - We introduce a quantum Monte Carlo method at finite temperature for interacting
fermionic models in the canonical ensemble, where the conservation of the
particle number is enforced. Although general thermodynamic arguments ensure the
equivalence of the canonical and the grand-canonical ensembles in the
thermodynamic limit, their approach to the infinite-volume limit is distinctively
different. Observables computed in the canonical ensemble generically display a
finite-size correction proportional to the inverse volume, whereas in the grand
canonical ensemble the approach is exponential in the ratio of the linear size
over the correlation length. We verify these predictions by quantum Monte Carlo
simulations of the Hubbard model in one and two dimensions in the grand-canonical
and the canonical ensemble. We prove an exact formula for the finite-size part of
the free energy density, energy density and other observables in the canonical
ensemble and relate this correction to a susceptibility computed in the
corresponding grand-canonical ensemble. This result is confirmed by an exact
computation of the one-dimensional classical Ising model in the canonical
ensemble, which for classical models corresponds to the so-called fixed
magnetization ensemble. Our method is useful for simulating finite systems which
are not coupled to a particle bath, such as in nuclear or cold atom physics.
PMID- 29347589
TI - Synchronization scenarios in the Winfree model of coupled oscillators.
AB - Fifty years ago Arthur Winfree proposed a deeply influential mean-field model for
the collective synchronization of large populations of phase oscillators. Here we
provide a detailed analysis of the model for some special, analytically tractable
cases. Adopting the thermodynamic limit, we derive an ordinary differential
equation that exactly describes the temporal evolution of the macroscopic
variables in the Ott-Antonsen invariant manifold. The low-dimensional model is
then thoroughly investigated for a variety of pulse types and sinusoidal phase
response curves (PRCs). Two structurally different synchronization scenarios are
found, which are linked via the mutation of a Bogdanov-Takens point. From our
results, we infer a general rule of thumb relating pulse shape and PRC offset
with each scenario. Finally, we compare the exact synchronization threshold with
the prediction of the averaging approximation given by the Kuramoto-Sakaguchi
model. At the leading order, the discrepancy appears to behave as an odd function
of the PRC offset.
PMID- 29347590
TI - Emergent Levy behavior in single-cell stochastic gene expression.
AB - Single-cell gene expression is inherently stochastic; its emergent behavior can
be defined in terms of the chemical master equation describing the evolution of
the mRNA and protein copy numbers as the latter tends to infinity. We establish
two types of "macroscopic limits": the Kurtz limit is consistent with the
classical chemical kinetics, while the Levy limit provides a theoretical
foundation for an empirical equation proposed in N. Friedman et al., Phys. Rev.
Lett. 97, 168302 (2006)PRLTAO0031-900710.1103/PhysRevLett.97.168302. Furthermore,
we clarify the biochemical implications and ranges of applicability for various
macroscopic limits and calculate a comprehensive analytic expression for the
protein concentration distribution in autoregulatory gene networks. The
relationship between our work and modern population genetics is discussed.
PMID- 29347591
TI - Reconstruction of three-dimensional porous media using generative adversarial
neural networks.
AB - To evaluate the variability of multiphase flow properties of porous media at the
pore scale, it is necessary to acquire a number of representative samples of the
void-solid structure. While modern x-ray computer tomography has made it possible
to extract three-dimensional images of the pore space, assessment of the
variability in the inherent material properties is often experimentally not
feasible. We present a method to reconstruct the solid-void structure of porous
media by applying a generative neural network that allows an implicit description
of the probability distribution represented by three-dimensional image data sets.
We show, by using an adversarial learning approach for neural networks, that this
method of unsupervised learning is able to generate representative samples of
porous media that honor their statistics. We successfully compare measures of
pore morphology, such as the Euler characteristic, two-point statistics, and
directional single-phase permeability of synthetic realizations with the
calculated properties of a bead pack, Berea sandstone, and Ketton limestone.
Results show that generative adversarial networks can be used to reconstruct high
resolution three-dimensional images of porous media at different scales that are
representative of the morphology of the images used to train the neural network.
The fully convolutional nature of the trained neural network allows the
generation of large samples while maintaining computational efficiency. Compared
to classical stochastic methods of image reconstruction, the implicit
representation of the learned data distribution can be stored and reused to
generate multiple realizations of the pore structure very rapidly.
PMID- 29347592
TI - Diffusion, subdiffusion, and localization of active colloids in random post
lattices.
AB - Combining experiments and theory, we address the dynamics of self-propelled
particles in crowded environments. We first demonstrate that motile colloids
cruising at constant speed through random lattices undergo a smooth transition
from diffusive to subdiffusive to localized dynamics upon increasing the obstacle
density. We then elucidate the nature of these transitions by performing
extensive simulations constructed from a detailed analysis of the colloid
obstacle interactions. We evidence that repulsion at a distance and hard-core
interactions both contribute to slowing down the long-time diffusion of the
colloids. In contrast, the localization transition stems solely from excluded
volume interactions and occurs at the void-percolation threshold. Within this
critical scenario, equivalent to that of the random Lorentz gas, genuine
asymptotic subdiffusion is found only at the critical density where the motile
particles explore a fractal maze.
PMID- 29347593
TI - Phase behavior and bulk structural properties of a microphase former with
anisotropic competing interactions: A density functional theory study.
AB - Using classical density functional theory, we investigate systems exhibiting
interactions where a short-range anisotropic attractive force competes with a
long-range spherically symmetric repulsive force. The former is modelled within
Wertheim's first-order perturbation theory for patchy particles, and the
repulsive part is assumed to be a Yukawa potential which is taken into account
via a mean-field approximation. From previous studies of systems with spherically
symmetric competing interactions, it is well known that such systems can exhibit
stable bulk cluster phases (microphase separation) provided that the repulsion is
sufficiently weak compared to the attraction. For the present model system, we
find rich phase diagrams including both reentrant clustering and liquid-gas
binodals. In particular, the model predicts inhomogeneous bulk phases at
extremely low packing fractions, which cannot be observed in systems with
isotropic competing interactions.
PMID- 29347594
TI - Cell-size distribution and scaling in a one-dimensional Kolmogorov-Johnson-Mehl
Avrami lattice model with continuous nucleation.
AB - The Kolmogorov-Johnson-Mehl-Avrami (KJMA) growth model is considered on a one
dimensional (1D) lattice. Cells can grow with constant speed and continuously
nucleate on the empty sites. We offer an alternative mean-field-like approach for
describing theoretically the dynamics and derive an analytical cell-size
distribution function. Our method reproduces the same scaling laws as the KJMA
theory and has the advantage that it leads to a simple closed form for the cell
size distribution function. It is shown that a Weibull distribution is
appropriate for describing the final cell-size distribution. The results are
discussed in comparison with Monte Carlo simulation data.
PMID- 29347595
TI - Coupling-enhanced stochastic resonance.
AB - Stochastic resonance is analyzed in an array of nonlinear spatially coupled
subsystems. Analytic expressions for the different steady-state solutions, for
the rates of transitions between them in the presence of noise, and for the
response to a weak external periodic forcing are derived. It is shown that the
presence of spatial degrees of freedom modifies considerably the mechanisms of
transitions between states and is responsible for a marked sensitivity of the
response on the coupling constant and on the system size.
PMID- 29347596
TI - Generalized fractional diffusion equations for subdiffusion in arbitrarily
growing domains.
AB - The ubiquity of subdiffusive transport in physical and biological systems has led
to intensive efforts to provide robust theoretical models for this phenomena.
These models often involve fractional derivatives. The important physical
extension of this work to processes occurring in growing materials has proven
highly nontrivial. Here we derive evolution equations for modeling subdiffusive
transport in a growing medium. The derivation is based on a continuous-time
random walk. The concise formulation of these evolution equations requires the
introduction of a new, comoving, fractional derivative. The implementation of the
evolution equation is illustrated with a simple model of subdiffusing proteins in
a growing membrane.
PMID- 29347597
TI - General purpose graphics-processing-unit implementation of cosmological domain
wall network evolution.
AB - Topological defects unavoidably form at symmetry breaking phase transitions in
the early universe. To probe the parameter space of theoretical models and set
tighter experimental constraints (exploiting the recent advances in astrophysical
observations), one requires more and more demanding simulations, and therefore
more hardware resources and computation time. Improving the speed and efficiency
of existing codes is essential. Here we present a general purpose graphics
processing-unit implementation of the canonical Press-Ryden-Spergel algorithm for
the evolution of cosmological domain wall networks. This is ported to the Open
Computing Language standard, and as a consequence significant speedups are
achieved both in two-dimensional (2D) and 3D simulations.
PMID- 29347598
TI - Electric generation and ratcheted transport of contact-charged drops.
AB - We describe a simple microfluidic system that enables the steady generation and
efficient transport of aqueous drops using only a constant voltage input. Drop
generation is achieved through an electrohydrodynamic dripping mechanism by which
conductive drops grow and detach from a grounded nozzle in response to an
electric field. The now-charged drops are transported down a ratcheted channel by
contact charge electrophoresis powered by the same voltage input used for drop
generation. We investigate how the drop size, generation frequency, and transport
velocity depend on system parameters such as the liquid viscosity, interfacial
tension, applied voltage, and channel dimensions. The observed trends are well
explained by a series of scaling analyses that provide insight into the dominant
physical mechanisms underlying drop generation and ratcheted transport. We
identify the conditions necessary for achieving reliable operation and discuss
the various modes of failure that can arise when these conditions are violated.
Our results demonstrate that simple electric inputs can power increasingly
complex droplet operations with potential opportunities for inexpensive and
portable microfluidic systems.
PMID- 29347599
TI - Energy decay in a tapped granular column: Can a one-dimensional toy model provide
insight into fully three-dimensional systems?
AB - The decay of energy within particulate media subjected to an impulse is an issue
of significant scientific interest, but also one with numerous important
practical applications. In this paper, we study the dynamics of a granular system
exposed to energetic impulses in the form of discrete taps from a solid surface.
By considering a one-dimensional toy system, we develop a simple theory, which
successfully describes the energy decay within the system following exposure to
an impulse. We then extend this theory so as to make it applicable also to more
realistic, three-dimensional granular systems, assessing the validity of the
model through direct comparison with discrete particle method simulations. The
theoretical form presented possesses several notable consequences; in particular,
it is demonstrated that for suitably large systems, effects due to the bounding
walls may be entirely neglected. We also establish the existence of a threshold
system size above which a granular bed may be considered fully three dimensional.
PMID- 29347600
TI - Liquidlike sloshing dynamics of monodisperse granulate.
AB - Analogies between fluid flows and granular flows are useful because they pave the
way for continuum treatments of granular media. However, in practice it is
impossible to predict under what experimental conditions the dynamics of fluids
and granulates are qualitatively similar. In the case of unsteadily driven
systems no such analogy is known. For example, in a partially filled container
subject to horizontal oscillations liquids slosh, whereas granular media of
complex particles exhibit large-scale convection rolls. We here show that smooth
monodisperse steel spheres exhibit liquidlike sloshing dynamics. Our findings
highlight the role of particle material and geometry for the dynamics and phase
transitions of the system.
PMID- 29347601
TI - Chaos-assisted tunneling in the presence of Anderson localization.
AB - Tunneling between two classically disconnected regular regions can be strongly
affected by the presence of a chaotic sea in between. This phenomenon, known as
chaos-assisted tunneling, gives rise to large fluctuations of the tunneling rate.
Here we study chaos-assisted tunneling in the presence of Anderson localization
effects in the chaotic sea. Our results show that the standard tunneling rate
distribution is strongly modified by localization, going from the Cauchy
distribution in the ergodic regime to a log-normal distribution in the strongly
localized case, for both a deterministic and a disordered model. We develop a
single-parameter scaling description which accurately describes the numerical
data. Several possible experimental implementations using cold atoms, photonic
lattices, or microwave billiards are discussed.
PMID- 29347602
TI - Control of accuracy in the Wang-Landau algorithm.
AB - The Wang-Landau (WL) algorithm has been widely used for simulations in many areas
of physics. Our analysis of the WL algorithm explains its properties and shows
that the difference of the largest eigenvalue of the transition matrix in the
energy space from unity can be used to control the accuracy of estimating the
density of states. Analytic expressions for the matrix elements are given in the
case of the one-dimensional Ising model. The proposed method is further confirmed
by numerical results for the one-dimensional and two-dimensional Ising models and
also the two-dimensional Potts model.
PMID- 29347603
TI - Asymmetric noise-induced large fluctuations in coupled systems.
AB - Networks of interacting, communicating subsystems are common in many fields, from
ecology, biology, and epidemiology to engineering and robotics. In the presence
of noise and uncertainty, interactions between the individual components can lead
to unexpected complex system-wide behaviors. In this paper, we consider a generic
model of two weakly coupled dynamical systems, and we show how noise in one part
of the system is transmitted through the coupling interface. Working
synergistically with the coupling, the noise on one system drives a large
fluctuation in the other, even when there is no noise in the second system.
Moreover, the large fluctuation happens while the first system exhibits only
small random oscillations. Uncertainty effects are quantified by showing how
characteristic time scales of noise-induced switching scale as a function of the
coupling between the two coupled parts of the experiment. In addition, our
results show that the probability of switching in the noise-free system scales
inversely as the square of reduced noise intensity amplitude, rendering the
virtual probability of switching an extremely rare event. Our results showing the
interplay between transmitted noise and coupling are also confirmed through
simulations, which agree quite well with analytic theory.
PMID- 29347604
TI - Capillary fluctuations of surface steps: An atomistic simulation study for the
model Cu(111) system.
AB - Molecular dynamics (MD) simulations are employed to investigate the capillary
fluctuations of steps on the surface of a model metal system. The fluctuation
spectrum, characterized by the wave number (k) dependence of the mean squared
capillary-wave amplitudes and associated relaxation times, is calculated for
<110> and <112> steps on the {111} surface of elemental copper near the melting
temperature of the classical potential model considered. Step stiffnesses are
derived from the MD results, yielding values from the largest system sizes of
(37+/-1)meV/A[over ] for the different line orientations, implying that the
stiffness is isotropic within the statistical precision of the calculations. The
fluctuation lifetimes are found to vary by approximately four orders of magnitude
over the range of wave numbers investigated, displaying a k dependence consistent
with kinetics governed by step-edge mediated diffusion. The values for step
stiffness derived from these simulations are compared to step free energies for
the same system and temperature obtained in a recent MD-based thermodynamic
integration (TI) study [Freitas, Frolov, and Asta, Phys. Rev. B 95, 155444
(2017)2469-995010.1103/PhysRevB.95.155444]. Results from the capillary
fluctuation analysis and TI calculations yield statistically significant
differences that are discussed within the framework of statistical-mechanical
theories for configurational contributions to step free energies.
PMID- 29347605
TI - Classical many-particle systems with unique disordered ground states.
AB - Classical ground states (global energy-minimizing configurations) of many
particle systems are typically unique crystalline structures, implying zero
enumeration entropy of distinct patterns (aside from trivial symmetry
operations). By contrast, the few previously known disordered classical ground
states of many-particle systems are all high-entropy (highly degenerate) states.
Here we show computationally that our recently proposed "perfect-glass" many
particle model [Sci. Rep. 6, 36963 (2016)10.1038/srep36963] possesses disordered
classical ground states with a zero entropy: a highly counterintuitive situation
. For all of the system sizes, parameters, and space dimensions that we have
numerically investigated, the disordered ground states are unique such that they
can always be superposed onto each other or their mirror image. At low energies,
the density of states obtained from simulations matches those calculated from the
harmonic approximation near a single ground state, further confirming ground
state uniqueness. Our discovery provides singular examples in which entropy and
disorder are at odds with one another. The zero-entropy ground states provide a
unique perspective on the celebrated Kauzmann-entropy crisis in which the
extrapolated entropy of a supercooled liquid drops below that of the crystal. We
expect that our disordered unique patterns to be of value in fields beyond glass
physics, including applications in cryptography as pseudorandom functions with
tunable computational complexity.
PMID- 29347606
TI - Coupling of link- and node-ordering in the coevolving voter model.
AB - We consider the process of reaching the final state in the coevolving voter
model. There is a coevolution of state dynamics, where a node can copy a state
from a random neighbor with probabilty 1-p and link dynamics, where a node can
rewire its link to another node of the same state with probability p. That
exhibits an absorbing transition to a frozen phase above a critical value of
rewiring probability. Our analytical and numerical studies show that in the
active phase mean values of magnetization of nodes n and links m tend to the same
value that depends on initial conditions. In a similar way mean degrees of spins
up and spins down become equal. The system obeys a special statistical
conservation law since a linear combination of both types magnetizations averaged
over many realizations starting from the same initial conditions is a constant of
motion: Lambda=(1-p)MUm(t)+pn(t)=const., where MU is the mean node degree. The
final mean magnetization of nodes and links in the active phase is proportional
to Lambda while the final density of active links is a square function of Lambda.
If the rewiring probability is above a critical value and the system separates
into disconnected domains, then the values of nodes and links magnetizations are
not the same and final mean degrees of spins up and spins down can be different.
PMID- 29347607
TI - Direct measurement of the ballistic motion of a freely floating colloid in
Newtonian and viscoelastic fluids.
AB - A thermal colloid suspended in a liquid will transition from a short-time
ballistic motion to a long-time diffusive motion. However, the transition between
ballistic and diffusive motion is highly dependent on the properties and
structure of the particular liquid. We directly observe a free floating tracer
particle's ballistic motion and its transition to the long-time regime in both a
Newtonian fluid and a viscoelastic Maxwell fluid. We examine the motion of the
free particle in a Newtonian fluid and demonstrate a high degree of agreement
with the accepted Clercx-Schram model for motion in a dense fluid. Measurements
of the functional form of the ballistic-to-diffusive transition provide direct
measurements of the temperature, viscosity, and tracer radius. We likewise
measure the motion in a viscoelastic Maxwell fluid and find a significant
disagreement between the theoretical asymptotic behavior and our measured values
of the microscopic properties of the fluid. We observe a greatly increased
effective mass for a freely moving particle and a decreased plateau modulus.
PMID- 29347608
TI - Mapping and discrimination of networks in the complexity-entropy plane.
AB - Complex networks are usually characterized in terms of their topological,
spatial, or information-theoretic properties and combinations of the associated
metrics are used to discriminate networks into different classes or categories.
However, even with the present variety of characteristics at hand it still
remains a subject of current research to appropriately quantify a network's
complexity and correspondingly discriminate between different types of complex
networks, like infrastructure or social networks, on such a basis. Here we
explore the possibility to classify complex networks by means of a statistical
complexity measure that has formerly been successfully applied to distinguish
different types of chaotic and stochastic time series. It is composed of a
network's averaged per-node entropic measure characterizing the network's
information content and the associated Jenson-Shannon divergence as a measure of
disequilibrium. We study 29 real-world networks and show that networks of the
same category tend to cluster in distinct areas of the resulting complexity
entropy plane. We demonstrate that within our framework, connectome networks
exhibit among the highest complexity while, e.g., transportation and
infrastructure networks display significantly lower values. Furthermore, we
demonstrate the utility of our framework by applying it to families of random
scale-free and Watts-Strogatz model networks. We then show in a second
application that the proposed framework is useful to objectively construct
threshold-based networks, such as functional climate networks or recurrence
networks, by choosing the threshold such that the statistical network complexity
is maximized.
PMID- 29347609
TI - Noise-induced drift in two-dimensional anisotropic systems.
AB - We study the isothermal Brownian dynamics of a particle in a system with
spatially varying diffusivity. Due to the heterogeneity of the system, the
particle's mean displacement does not vanish even if it does not experience any
physical force. This phenomenon has been termed "noise-induced drift," and has
been extensively studied for one-dimensional systems. Here, we examine the noise
induced drift in a two-dimensional anisotropic system, characterized by a
symmetric diffusion tensor with unequal diagonal elements. A general expression
for the mean displacement vector is derived and presented as a sum of two
vectors, depicting two distinct drifting effects. The first vector describes the
tendency of the particle to drift toward the high diffusivity side in each
orthogonal principal diffusion direction. This is a generalization of the well
known expression for the noise-induced drift in one-dimensional systems. The
second vector represents a novel drifting effect, not found in one-dimensional
systems, originating from the spatial rotation in the directions of the principal
axes. The validity of the derived expressions is verified by using Langevin
dynamics simulations. As a specific example, we consider the relative diffusion
of two transmembrane proteins, and demonstrate that the average distance between
them increases at a surprisingly fast rate of several tens of micrometers per
second.
PMID- 29347610
TI - Relaxation time of the global order parameter on multiplex networks: The role of
interlayer coupling in Kuramoto oscillators.
AB - This work considers the time scales associated with the global order parameter
and the interlayer synchronization of coupled Kuramoto oscillators on
multiplexes. For two-layer multiplexes with an initially high degree of
synchronization in each layer, the difference between the average phases in each
layer is analyzed from two different perspectives: the spectral analysis and the
nonlinear Kuramoto model. Both viewpoints confirm that the prior time scales are
inversely proportional to the interlayer coupling strength. Thus, increasing the
interlayer coupling always shortens the transient regimes of both the global
order parameter and the interlayer synchronization. Surprisingly, the analytical
results show that the convergence of the global order parameter is faster than
the interlayer synchronization, and the latter is generally faster than the
global synchronization of the multiplex. The formalism also outlines the effects
of frequencies on the difference between the average phases of each layer, and it
identifies the conditions for an oscillatory behavior. Computer simulations are
in fairly good agreement with the analytical findings, and they reveal that the
time scale of the global order parameter is half the size of the time scale of
the multiplex, if not smaller.
PMID- 29347611
TI - Iterated function systems for DNA replication.
AB - The kinetic equations of DNA replication are shown to be exactly solved in terms
of iterated function systems, running along the template sequence and giving the
statistical properties of the copy sequences, as well as the kinetic and
thermodynamic properties of the replication process. With this method, different
effects due to sequence heterogeneity can be studied, in particular, a transition
between linear and sublinear growths in time of the copies, and a transition
between continuous and fractal distributions of the local velocities of the DNA
polymerase along the template. The method is applied to the human mitochondrial
DNA polymerase gamma without and with exonuclease proofreading.
PMID- 29347612
TI - Biological cell as a soft magnetoelectric material: Elucidating the physical
mechanisms underpinning the detection of magnetic fields by animals.
AB - Sharks, birds, bats, turtles, and many other animals can detect magnetic fields.
Aside from using this remarkable ability to exploit the terrestrial magnetic
field map to sense direction, a subset is also able to implement a version of the
so-called geophysical positioning system. How do these animals detect magnetic
fields? The answer to this rather deceptively simple question has proven to be
quite elusive. The currently prevalent theories, while providing interesting
insights, fall short of explaining several aspects of magnetoreception. For
example, minute magnetic particles have been detected in magnetically sensitive
animals. However, how is the detected magnetic field converted into electrical
signals given any lack of experimental evidence for relevant electroreceptors? In
principle, a magnetoelectric material is capable of converting magnetic signals
into electricity (and vice versa). This property, however, is rare and restricted
to a rather small set of exotic hard crystalline materials. Indeed, such elements
have never been detected in the animals studied so far. In this work we
quantitatively outline the conditions under which a biological cell may detect a
magnetic field and convert it into electrical signals detectable by biological
cells. Specifically, we prove the existence of an overlooked strain-mediated
mechanism and show that most biological cells can act as nontrivial
magnetoelectric materials provided that the magnetic permeability constant is
only slightly more than that of a vacuum. The enhanced magnetic permeability is
easily achieved by small amounts of magnetic particles that have been
experimentally detected in magnetosensitive animals. Our proposed mechanism
appears to explain most of the experimental observations related to the physical
basis of magnetoreception.
PMID- 29347613
TI - Test of the diffusing-diffusivity mechanism using near-wall colloidal dynamics.
AB - The mechanism of diffusing diffusivity predicts that, in environments where the
diffusivity changes gradually, the displacement distribution becomes non
Gaussian, even though the mean-square displacement grows linearly with time.
Here, we report single-particle tracking measurements of the diffusion of
colloidal spheres near a planar substrate. Because the local effective
diffusivity is known, we have been able to carry out a direct test of this
mechanism for diffusion in inhomogeneous media.
PMID- 29347614
TI - Analysis of crackling noise using the maximum-likelihood method: Power-law mixing
and exponential damping.
AB - Crackling noise can be initiated by competing or coexisting mechanisms. These
mechanisms can combine to generate an approximate scale invariant distribution
that contains two or more contributions. The overall distribution function can be
analyzed, to a good approximation, using maximum-likelihood methods and assuming
that it follows a power law although with nonuniversal exponents depending on a
varying lower cutoff. We propose that such distributions are rather common and
originate from a simple superposition of crackling noise distributions or
exponential damping.
PMID- 29347615
TI - Publisher's Note: Critical and Griffiths-McCoy singularities in quantum Ising
spin glasses on d-dimensional hypercubic lattices: A series expansion study
[Phys. Rev. E 96, 022139 (2017)].
AB - This corrects the article DOI: 10.1103/PhysRevE.96.022139.
PMID- 29347616
TI - Design and investigation of de Vries liquid crystals based on 5-phenyl-pyrimidine
and (R,R)-2,3-epoxyhexoxy backbone.
AB - Calamitic liquid crystals based on 5-phenyl-pyrimidine derivatives have been
designed, synthesized, and characterized. The 5-phenyl pyrimidine core was
functionalized with a chiral (R,R)-2,3-epoxyhexoxy chain on one side and either
siloxane or perfluoro terminated chains on the opposite side. The one involving a
perfluorinated chain shows SmA^{*} phase over a wide temperature range of 82
degrees C, whereas the siloxane analog exhibits both SmA^{*} and SmC^{*} phases
over a broad range of temperatures, and a weak first-order SmA^{*}-SmC^{*}
transition is observed. For the siloxane analog, the reduction factor for the
layer shrinkage R (relative to its thickness at the SmA^{*}-SmC^{*} transition
temperature, T_{AC}) is ~0.373, and layer shrinkage is 1.7% at a temperature of
13 degrees C below the T_{AC}. This compound is considered to have "de Vries
smectic" characteristics with the de Vries coefficient C_{deVries} of ~0.86 on
the scale of zero (maximum-layer shrinkage) to 1 (zero-layer shrinkage). A three
parameter mean-field model is introduced for the orientational distribution
function (ODF) to reproduce the electro-optic properties. This model explains the
experimental results and leads to the ODF, which exhibits a crossover from the
sugar-loaf to diffuse-cone ODF some 3 degrees C above T_{AC}.
PMID- 29347617
TI - Force percolation transition of jammed granular systems.
AB - The mechanical and transport properties of jammed materials originate from an
underlying percolating network of contact forces between the grains. Using
extensive simulations we investigate the force-percolation transition of this
network, where two particles are considered as linked if their interparticle
force overcomes a threshold. We show that this transition belongs to the random
percolation universality class, thus ruling out the existence of long-range
correlations between the forces. Through a combined size and pressure scaling for
the percolative quantities, we show that the continuous force percolation
transition evolves into the discontinuous jamming transition in the zero pressure
limit, as the size of the critical region scales with the pressure.
PMID- 29347618
TI - Universality of oscillating boiling in Leidenfrost transition.
AB - The Leidenfrost transition leads a boiling system to the boiling crisis, a state
in which the liquid loses contact with the heated surface due to excessive vapor
generation. Here, using experiments of liquid droplets boiling on a heated
surface, we report a phenomenon, termed oscillating boiling, at the Leidenfrost
transition. We show that oscillating boiling results from the competition between
two effects: separation of liquid from the heated surface due to localized
boiling and rewetting. We argue theoretically that the Leidenfrost transition can
be predicted based on its link with the oscillating boiling phenomenon and verify
the prediction experimentally for various liquids.
PMID- 29347619
TI - Topological defects in an unconfined nematic fluid induced by single and double
spherical colloidal particles.
AB - We present numerical solutions to the Landau-de Gennes free-energy model under
the one-constant approximation for systems of single and double spherical
colloidal particles immersed in an otherwise uniformly aligned nematic liquid
crystal. A perfect homeotropic surface anchoring of liquid-crystal molecules on
the spherical surface is considered. A large parameter space is carefully
examined, including those in the free-energy model and those describing the dimer
configurations and the background liquid-crystal orientation. The stability of
the resulting liquid-crystal defects appearing in the neighborhood of the
colloidal dimer pair is analyzed in light of the numerical results for their free
energies. A number of scenarios are considered: a free dimer pair in a nematic
fluid where the free-energy ground states are described in terms of a phase
diagram, and a constrained dimer pair where the interparticle distance and the
relative orientation of the distance vector to the nematic director can be
manipulated. We pay particular attention to the nonsymmetric solutions, which
yield several metastable defect states that can be observed in real systems. The
high-precision numerical calculations are based on a spectral method, which is an
enabling factor that allows us to compare the subtle difference in the free
energies of different defect structures.
PMID- 29347620
TI - Suppression of crystalline fluctuations by competing structures in a supercooled
liquid.
AB - We propose a geometrical characterization of amorphous liquid structures that
suppress crystallization by competing locally with crystalline order. We
introduce for this purpose the crystal affinity of a liquid, a simple measure of
its propensity to accumulate local crystalline structures on cooling. This
quantity is explicitly related to the high-temperature structural covariance
between local fluctuations in crystal order and that of competing liquid
structures: favoring a structure that, due to poor overlap properties,
anticorrelates with crystalline order reduces the affinity of the liquid. Using a
lattice model of a liquid, we show that this quantity successfully predicts the
tendency of a liquid to either accumulate or suppress local crystalline
fluctuations with increasing supercooling. We demonstrate that the crystal
affinity correlates strongly with the crystal nucleation rate and the crystal
liquid interfacial free energy of the low-temperature liquid, making our theory a
predictive tool to determine which amorphous structures enhance glass-forming
ability.
PMID- 29347621
TI - Transient anomalous diffusion regimes in reversible adsorbing systems.
AB - A solvable, minimal model of diffusion in the presence of a reversible adsorption
site is investigated. We show that the diffusive particles are influenced by the
adsorbing site on transient times when they have anomalous subdiffusive behavior.
However, the particle dispersion law crosses over to the normal diffusive regime
on asymptotically long times. The subdiffusive regime is characterized by a
t^{1/4} transient scaling with the same exponent as for the irreversible
adsorption. On this transient time scale dominated by particle adsorption, there
is a depletion of particles near the adsorbing site, and the typical width of the
depletion zone grows in time as t^{1/4} with the same exponent as the
subdiffusive dispersion. We show that having a nonzero desorption probability for
the adsorbed particles produces a crossover towards normal diffusion on time
scales larger than a characteristic reactive time, which we show scales with
diffusivity and the adsorption site reactivity.
PMID- 29347622
TI - Transport regimes spanning magnetization-coupling phase space.
AB - The manner in which transport properties vary over the entire parameter-space of
coupling and magnetization strength is explored. Four regimes are identified
based on the relative size of the gyroradius compared to other fundamental length
scales: the collision mean free path, Debye length, distance of closest approach,
and interparticle spacing. Molecular dynamics simulations of self-diffusion and
temperature anisotropy relaxation spanning the parameter space are found to agree
well with the predicted boundaries. Comparison with existing theories reveals
regimes where they succeed, where they fail, and where no theory has yet been
developed.
PMID- 29347623
TI - Origin of the inertial deviation from Darcy's law: An investigation from a
microscopic flow analysis on two-dimensional model structures.
AB - Inertial flow in porous media occurs in many situations of practical relevance
among which one can cite flows in column reactors, in filters, in aquifers, or
near wells for hydrocarbon recovery. It is characterized by a deviation from
Darcy's law that leads to a nonlinear relationship between the pressure drop and
the filtration velocity. In this work, this deviation, also known as the
nonlinear, inertial, correction to Darcy's law, which is subject to controversy
upon its origin and dependence on the filtration velocity, is studied through
numerical simulations. First, the microscopic flow problem was solved
computationally for a wide range of Reynolds numbers up to the limit of steady
flow within ordered and disordered porous structures. In a second step, the
macroscopic characteristics of the porous medium and flow (permeability and
inertial correction tensors) that appear in the macroscale model were computed.
From these results, different flow regimes were identified: (1) the weak inertia
regime where the inertial correction has a cubic dependence on the filtration
velocity and (2) the strong inertia (Forchheimer) regime where the inertial
correction depends on the square of the filtration velocity. However, the
existence and origin of those regimes, which depend also on the microstructure
and flow orientation, are still not well understood in terms of their physical
interpretations, as many causes have been conjectured in the literature. In the
present study, we provide an in-depth analysis of the flow structure to identify
the origin of the deviation from Darcy's law. For accuracy and clarity purposes,
this is carried out on two-dimensional structures. Unlike the previous studies
reported in the literature, where the origin of inertial effects is often
identified on a heuristic basis, a theoretical justification is presented in this
work. Indeed, a decomposition of the convective inertial term into two components
is carried out formally allowing the identification of a correlation between the
flow structure and the different inertial regimes. These components correspond to
the curvature of the flow streamlines weighted by the local fluid kinetic energy
on the one hand and the distribution of the kinetic energy along these lines on
the other hand. In addition, the role of the recirculation zones in the
occurrence and in the form of the deviation from Darcy's law was thoroughly
analyzed. For the porous structures under consideration, it is shown that (1) the
kinetic energy lost in the vortices is insignificant even at high filtration
velocities and (2) the shape of the flow streamlines induced by the recirculation
zones plays an important role in the variation of the flow structure, which is
correlated itself to the different flow regimes.
PMID- 29347624
TI - Non-Poisson renewal events and memory.
AB - We study two different forms of fluctuation-dissipation processes generating
anomalous relaxations to equilibrium of an initial out-of-equilibrium condition,
the former being based on a stationary although very slow correlation function
and the latter characterized by the occurrence of crucial events, namely, non
Poisson renewal events, incompatible with the stationary condition. Both forms of
regression to equilibrium have the same nonexponential Mittag-Leffler structure.
We analyze the single trajectories of the two processes by recording the time
distances between two consecutive origin recrossings and establishing the
corresponding waiting time probability density function (PDF), psi(t). In the
former case, with no crucial events, psi(t) is an exponential, and in the latter
case, with crucial events, psi(t) is an inverse power law PDF with a diverging
first moment. We discuss the consequences that this result is expected to have
for the correct interpretation of some anomalous relaxation processes.
PMID- 29347625
TI - Modeling of the interaction of an x-ray free-electron laser with large finite
samples.
AB - We describe a model for the study of the interaction of short x-ray free-electron
laser (XFEL) pulses with large finite samples. Hydrodynamics is solved in one
dimensional planar geometry with consideration of the electron-ion energy
exchange and of the possible elastoplastic behavior. From a time-dependent
calculation of the complex refractive index and of the underlying atomic physics,
XFEL energy deposition is modeled through a calculation of the radiation field in
the material. In the case of hard x-ray irradiation, energetic electrons induced
by the XFEL absorption can propagate and deposit their energy outside the
interaction region. Simulations of the interaction of hard x-ray ultrashort
pulses with solid materials Ru and Si at different grazing incidence angles are
presented and discussed. The results obtained demonstrate the potential of this
approach to predict damage dynamics for materials of interest for x-ray optics.
PMID- 29347626
TI - Langevin equation elucidates the mechanism of the Rayleigh-Benard instability by
coupling molecular motions and macroscopic fluctuations.
AB - It is well known that Brownian motion can be described using Langevin equation.
In this paper we extend the application of the Langevin equation to the Rayleigh
Benard (RB) flow, assuming that each molecule in the system is a Brownian
particle colliding with its surrounding molecules. The phenomenon of thermal
instability, changing from a conductive to a convective state, is well reproduced
by Langevin dynamics simulations. The roles of the drag force and the random
force terms in the Langevin equation in triggering thermal instability are
elucidated via numerical tests. Furthermore, we demonstrate that the strength of
the fluctuation correlations increases as the Rayleigh number approaches the
critical value, and the characteristics of the fluctuation correlations below the
onset of instability foreshadow the form of the convective patterns emerging
above the critical point. The Langevin equation, together with the form of the
fluctuation correlations, sheds new light on the mechanism of the RB instability.
PMID- 29347627
TI - Static and dynamic properties of two-dimensional Coulomb clusters.
AB - We study the temperature dependence of static and dynamic responses of Coulomb
interacting particles in two-dimensional confinements across the crossover from
solid- to liquid-like behaviors. While static correlations that investigate the
translational and bond orientational order in the confinements show the
footprints of hexatic-like phase at low temperatures, dynamics of the particles
slow down considerably in this phase, reminiscent of a supercooled liquid. Using
density correlations, we probe long-lived heterogeneities arising from the
interplay of the irregularity in the confinement and long-range Coulomb
interactions. The relaxation at multiple time scales show stretched-exponential
decay of spatial correlations in irregular traps. Temperature dependence of
characteristic time scales, depicting the structural relaxation of the system,
show striking similarities with those observed for the glassy systems, indicating
that some of the key signatures of supercooled liquids emerge in confinements
with lower spatial symmetries.
PMID- 29347628
TI - Opposing effects of cationic antimicrobial peptides and divalent cations on
bacterial lipopolysaccharides.
AB - The permeability of the bacterial outer membrane, enclosing Gram-negative
bacteria, depends on the interactions of the outer, lipopolysaccharide (LPS)
layer, with surrounding ions and molecules. We present a coarse-grained model for
describing how cationic amphiphilic molecules (e.g., antimicrobial peptides)
interact with and perturb the LPS layer in a biologically relevant medium,
containing monovalent and divalent salt ions (e.g., Mg^{2+}). In our approach,
peptide binding is driven by electrostatic and hydrophobic interactions and is
assumed to expand the LPS layer, eventually priming it for disruption. Our
results suggest that in parameter ranges of biological relevance (e.g., at
micromolar concentrations) the antimicrobial peptide magainin 2 effectively
disrupts the LPS layer, even though it has to compete with Mg^{2+} for the layer.
They also show how the integrity of LPS is restored with an increasing
concentration of Mg^{2+}. Using the approach, we make a number of predictions
relevant for optimizing peptide parameters against Gram-negative bacteria and for
understanding bacterial strategies to develop resistance against cationic
peptides.
PMID- 29347629
TI - Perturbative dynamics of open quantum systems by renormalization group method.
AB - We analyze perturbative dynamics of a composite system consisting of a quantum
mechanical system and an environment by the renormalization group (RG) method.
The solution obtained from the RG method has no secular terms and approximates
the exact solution for a long time interval. Moreover, the RG method causes a
reduction of the dynamics of the composite system under some assumptions. We show
that this reduced dynamics is closely related to a quantum master equation for
the quantum mechanical system. We compare this dynamics with the exact dynamics
in an exactly solvable spin-boson model.
PMID- 29347630
TI - Temperature measurement of hohlraum radiation for energy loss experiments in
indirectly laser heated carbon plasma.
AB - For ion energy loss measurements in plasmas with near solid densities, an
indirect laser heating scheme for carbon foils has been developed at GSI
Helmholtzzentrum fur Schwerionenforschung GmbH (Darmstadt, Germany). To achieve
an electron density of 10^{22}cm^{3} and an electron temperature of 10-30eV, two
carbon foils with an areal density of 100MUg/cm^{2} heated in a double-hohlraum
configuration have been chosen. In this paper we present the results of
temperature measurements of both primary and secondary hohlraums for two
different hohlraum designs. They were heated by the PHELIX laser with a
wavelength of 527nm and an energy of 150J in 1.5ns. For this purpose the
temperature has been investigated by an x-ray streak camera with a transmission
grating as the dispersive element.
PMID- 29347631
TI - Phase transitions in restricted Boltzmann machines with generic priors.
AB - We study generalized restricted Boltzmann machines with generic priors for units
and weights, interpolating between Boolean and Gaussian variables. We present a
complete analysis of the replica symmetric phase diagram of these systems, which
can be regarded as generalized Hopfield models. We underline the role of the
retrieval phase for both inference and learning processes and we show that
retrieval is robust for a large class of weight and unit priors, beyond the
standard Hopfield scenario. Furthermore, we show how the paramagnetic phase
boundary is directly related to the optimal size of the training set necessary
for good generalization in a teacher-student scenario of unsupervised learning.
PMID- 29347632
TI - Dynamics of a thermally driven film climbing the outside of a vertical cylinder.
AB - The dynamics of a film climbing the outside of a vertical cylinder under the
competing effects of a thermally driven surface tension gradient and gravity is
examined through numerical simulations of a thin-film model for the film height.
The model, including boundary conditions, depends on three parameters, the scaled
cylinder radius R[over ], the upstream film height h_{infinity}, and the
downstream precursor film thickness b, and reduces to the model for Marangoni
driven film climbing a vertical plate in the limit R[over ]->infinity. The
axisymmetric advancing front displays dynamics similar to that found along a
vertical plate where, depending on h_{infinity}, the film forms a single Lax
shock, an undercompressive double shock, or a rarefaction-undercompressive shock.
A linear stability analysis of the Lax shock reveals the number of fingers that
form along the contact line increases linearly with cylinder circumference while
no fingers form for sufficiently small cylinders (below R[over ]~1.15 when
b=0.1). The substrate curvature controls the height of the Lax shock, bounds on
h_{infinity} that define the three distinct solutions, and the maximum growth
rate of contact line perturbations to the Lax shock when R[over ]=O(1), whereas
the three solutions and the stability of the Lax shock converge to the behavior
one observes on a vertical plate when R[over ]>=O(10). An energy analysis reveals
that the azimuthal curvatures of the base state and perturbation, which arise
from the annular geometry of the film, promote instability of the advancing
contact line.
PMID- 29347633
TI - Stochastic thermodynamics of interacting degrees of freedom: Fluctuation theorems
for detached path probabilities.
AB - Systems with interacting degrees of freedom play a prominent role in stochastic
thermodynamics. Our aim is to use the concept of detached path probabilities and
detached entropy production for bipartite Markov processes and elaborate on a
series of special cases including measurement-feedback systems, sensors, and
hidden Markov models. For these special cases we show that fluctuation theorems
involving the detached entropy production recover known results which have been
obtained separately before. Additionally, we show that the fluctuation relation
for the detached entropy production can be used in model selection for data
stemming from a hidden Markov model. We discuss the relation to previous
approaches including those which use information flow or learning rate to
quantify the influence of one subsystem on the other. In conclusion, we present a
complete framework with which to find fluctuation relations for coupled systems.
PMID- 29347634
TI - Strong diffusion formulation of Markov chain ensembles and its optimal weaker
reductions.
AB - : Two self-contained diffusion formulations, in the form of coupled stochastic
differential equations, are developed for the temporal evolution of state
densities over an ensemble of Markov chains evolving independently under a common
transition rate matrix. Our first formulation derives from Kurtz's strong
approximation theorem of density-dependent Markov jump processes [Stoch. PROCESS:
Their Appl. 6, 223 (1978)STOPB70304-414910.1016/0304-4149(78)90020-0] and,
therefore, strongly converges with an error bound of the order of lnN/N for
ensemble size N. The second formulation eliminates some fluctuation variables,
and correspondingly some noise terms, within the governing equations of the
strong formulation, with the objective of achieving a simpler analytic
formulation and a faster computation algorithm when the transition rates are
constant or slowly varying. There, the reduction of the structural complexity is
optimal in the sense that the elimination of any given set of variables takes
place with the lowest attainable increase in the error bound. The resultant
formulations are supported by numerical simulations.
PMID- 29347635
TI - Classifying Potts critical lines.
AB - We use scale invariant scattering theory to exactly determine the lines of
renormalization group fixed points invariant under the permutational symmetry
S_{q} in two dimensions, and we show how one of these scattering solutions
describes the ferromagnetic and square lattice antiferromagnetic critical lines
of the q-state Potts model. Other solutions we determine should correspond to new
critical lines. In particular, we obtain that a S_{q}-invariant fixed point can
be found up to the maximal value q=(7+sqrt[17])/2. This is larger than the
usually assumed maximal value 4 and leaves room for a second-order
antiferromagnetic transition at q=5.
PMID- 29347636
TI - Glassy swirls of active dumbbells.
AB - Is an active glass different from a conventional passive glass? To address this,
we study the dynamics of a dense binary mixture of soft dumbbells, each subject
to an active propulsion force and thermal fluctuations. This dense assembly shows
dynamical arrest, first to a translational and then to a rotational glass, as one
reduces temperature T or the self-propulsion force f. We monitor the dynamics
along an iso-relaxation-time contour in the (T-f) plane. We find dramatic
differences both in the fragility and in the nature of dynamical heterogeneity,
which characterize the onset of glass formation-the activity-induced glass
exhibits large swirls or vortices, whose scale is set by activity, and it appears
to diverge as one approaches the glass transition. This large collective swirling
movement should have implications for collective cell migration in epithelial
layers. We construct continuum hydrodynamic equations for the simulated system,
and we show that the observed behavior of this growing dynamic length scale can
be understood from these equations.
PMID- 29347637
TI - Ideal radiation source for plasma spectroscopy generated by laser ablation.
AB - Laboratory plasmas inherently exhibit temperature and density gradients leading
to complex investigations. We show that plasmas generated by laser ablation can
constitute a robust exception to this. Supported by emission features not
observed with other sources, we achieve plasmas of various compositions which are
both uniform and in local thermodynamic equilibrium. These properties
characterize an ideal radiation source opening multiple perspectives in plasma
spectroscopy. The finding also constitutes a breakthrough in the analytical field
as fast analyses of complex materials become possible.
PMID- 29347638
TI - Effects of group velocity and multiplasmon resonances on the modulation of
Langmuir waves in a degenerate plasma.
AB - We study the nonlinear wave modulation of Langmuir waves (LWs) in a fully
degenerate plasma. Using the Wigner-Moyal equation coupled to the Poisson
equation and the multiple scale expansion technique, a modified nonlocal
nonlinear Schrodinger (NLS) equation is derived which governs the evolution of LW
envelopes in degenerate plasmas. The nonlocal nonlinearity in the NLS equation
appears due to the group velocity and multiplasmon resonances, i.e., resonances
induced by the simultaneous particle absorption of multiple wave quanta. We focus
on the regime where the resonant velocity of electrons is larger than the Fermi
velocity and thereby the linear Landau damping is forbidden. As a result, the
nonlinear wave-particle resonances due to the group velocity and multiplasmon
processes are the dominant mechanisms for wave-particle interaction. It is found
that in contrast to classical or semiclassical plasmas, the group velocity
resonance does not necessarily give rise the wave damping in the strong quantum
regime where hk~mv_{F} with h denoting the reduced Planck's constant, m the
electron mass, and v_{F} the Fermi velocity; however, the three-plasmon process
plays a dominant role in the nonlinear Landau damping of wave envelopes. In this
regime, the decay rate of the wave amplitude is also found to be higher compared
to that in the modest quantum regime where the multiplasmon effects are
forbidden.
PMID- 29347639
TI - Experimental realization of a minimal microscopic heat engine.
AB - Microscopic heat engines are microscale systems that convert energy flows between
heat reservoirs into work or systematic motion. We have experimentally realized a
minimal microscopic heat engine. It consists of a colloidal Brownian particle
optically trapped in an elliptical potential well and simultaneously coupled to
two heat baths at different temperatures acting along perpendicular directions.
For a generic arrangement of the principal directions of the baths and the
potential, the symmetry of the system is broken, such that the heat flow drives a
systematic gyrating motion of the particle around the potential minimum. Using
the experimentally measured trajectories, we quantify the gyrating motion of the
particle, the resulting torque that it exerts on the potential, and the
associated heat flow between the heat baths. We find excellent agreement between
the experimental results and the theoretical predictions.
PMID- 29347640
TI - Thermodynamic cost for classical counterdiabatic driving.
AB - Motivated by the recent growing interest about the thermodynamic cost of
shortcuts to adiabaticity, we consider the cost of driving a classical system by
the so-called counterdiabatic driving (CD). To do so, we proceed in three steps:
first we review a general definition recently put forward in the literature for
the thermodynamic cost of driving a Hamiltonian system; then we provide a new
complementary definition of cost, which is of particular relevance for cases
where the average excess work vanishes; finally, we apply our general framework
to the case of CD. Interestingly, we find that in such a case our results are the
exact classical counterparts of those reported by Funo et al. [Phys. Rev. Lett.
118, 100602 (2017)PRLTAO0031-900710.1103/PhysRevLett.118.100602]. In particular
we show that a universal trade-off between speed and cost for CD also exists in
the classical case. To illustrate our points we consider the example of a time
dependent harmonic oscillator subject to different strategies of adiabatic
control.
PMID- 29347641
TI - Sound-mediated stable configurations for polystyrene particles.
AB - Here we report an experimental observation of the self-organization effect of
polystyrene particles formed by acoustically induced interaction forces. Two
types of stable configurations are observed experimentally: one is mechanically
equilibrium and featured by nonzero interparticle separations, and the other
corresponds to a closely packed assembly, which is created by strong attractions
among the aggregated particles. For the former case involving two or three
particles, the most probable interparticle separations (counted for numerous
independent initial arrangements) agree well with the theoretical predictions.
For the latter case, the number of the final stable configurations grows with the
particle number, and the occurrence probability of each configuration is
interpreted by a simple geometric model.
PMID- 29347642
TI - Carpet cloak for water waves.
AB - Cloaking is a challenging topic in the field of wave motion, and is of
significant theoretical value. In this article, a type of carpet cloak has been
theoretically designed for water waves by using the effective medium and
transformation theory. This carpet cloak device, created by a three-dimensional
printer, is composed of a periodic structure which realizes the equivalent
anisotropic water depth. We demonstrate its excellent cloaking performance
numerically and experimentally in a wide range of frequencies and angles of
incidence, with low wave attenuation characteristics and simple device
realization of this carpet cloak illustrating that water wave transformation is a
powerful method with which to manipulate water waves.
PMID- 29347643
TI - Nonhelical turbulence and the inverse transfer of energy: A parameter study.
AB - We explore the phenomenon of the recently discovered inverse transfer of energy
from small to large scales in decaying magnetohydrodynamical turbulence by
Brandenburg et al. [Phys. Rev. Lett. 114, 075001 (2015)PRLTAO0031
900710.1103/PhysRevLett.114.075001], even for nonhelical magnetic fields. For
this investigation we mainly employ the Pencil Code performing a parameter study,
where we vary the Prandtl number, the kinematic viscosity, and the initial
spectrum. We find that to get a decay that exhibits this inverse transfer, large
Reynolds numbers (O~10^{3}) are needed and low Prandtl numbers of the order unity
Pr=1 are preferred. Compared to helical MHD turbulence, though, the inverse
transfer is much less efficient in transferring magnetic energy to larger scales
than the well-known effect of the inverse cascade. Hence, applying the inverse
transfer to the magnetic field evolution in the Early Universe, we question
whether the nonhelical inverse transfer is effective enough to explain the
observed void magnetic fields if a magnetogenesis scenario during the electroweak
phase transition is assumed.
PMID- 29347644
TI - Adiabatic cooling processes in frustrated magnetic systems with pyrochlore
structure.
AB - We investigate in detail the process of adiabatic cooling in the framework of the
exactly solvable antiferromagnetic spin-1/2 Ising model in the presence of the
external magnetic field on an approximate lattice with pyrochlore structure. The
behavior of the entropy of the model is studied and exact values of the residual
entropies of all ground states are found. The temperature variation of the system
under adiabatic (de)magnetization is investigated and the central role of the
macroscopically degenerated ground states in cooling processes is explicitly
demonstrated. It is shown that the model parameter space of the studied
geometrically frustrated system is divided into five disjunct regions with
qualitatively different processes of the adiabatic cooling. The effectiveness of
the adiabatic (de)magnetization cooling in the studied model is compared to the
corresponding processes in paramagnetic salts. It is shown that the processes of
the adiabatic cooling in the antiferromagnetic frustrated systems are much more
effective especially in nonzero external magnetic fields. It means that the
frustrated magnetic materials with pyrochlore structure can be considered as very
promising refrigerants mainly in the situations with nonzero final values of the
magnetic field.
PMID- 29347645
TI - Geometry and the onset of rigidity in a disordered network.
AB - Disordered spring networks that are undercoordinated may abruptly rigidify when
sufficient strain is applied. Since the deformation in response to applied strain
does not change the generic quantifiers of network architecture, the number of
nodes and the number of bonds between them, this rigidity transition must have a
geometric origin. Naive, degree-of-freedom-based mechanical analyses such as the
Maxwell-Calladine count or the pebble game algorithm overlook such geometric
rigidity transitions and offer no means of predicting or characterizing them. We
apply tools that were developed for the topological analysis of zero modes and
states of self-stress on regular lattices to two-dimensional random spring
networks and demonstrate that the onset of rigidity, at a finite simple shear
strain gamma^{?}, coincides with the appearance of a single state of self-stress,
accompanied by a single floppy mode. The process conserves the topologically
invariant difference between the number of zero modes and the number of states of
self-stress but imparts a finite shear modulus to the spring network. Beyond the
critical shear, the network acquires a highly anisotropic elastic modulus,
resisting further deformation most strongly in the direction of the rigidifying
shear. We confirm previously reported critical scaling of the corresponding
differential shear modulus. In the subcritical regime, a singular value
decomposition of the network's compatibility matrix foreshadows the onset of
rigidity by way of a continuously vanishing singular value corresponding to the
nascent state of self-stress.
PMID- 29347646
TI - Marangoni effect on small-amplitude capillary waves in viscous fluids.
AB - We derive a general integro-differential equation for the transient behavior of
small-amplitude capillary waves on the planar surface of a viscous fluid in the
presence of the Marangoni effect. The equation is solved for an insoluble
surfactant solution in concentration below the critical micelle concentration
undergoing convective-diffusive surface transport. The special case of a
diffusion-driven surfactant is considered near the the critical damping
wavelength. The Marangoni effect is shown to contribute to the overall damping
mechanism, and a first-order term correction to the critical wavelength with
respect to the surfactant concentration difference and the Schmidt number is
proposed.
PMID- 29347647
TI - Fast and slow domino regimes in transient network dynamics.
AB - It is well known that the addition of noise to a multistable dynamical system can
induce random transitions from one stable state to another. For low noise, the
times between transitions have an exponential tail and Kramers' formula gives an
expression for the mean escape time in the asymptotic limit. If a number of
multistable systems are coupled into a network structure, a transition at one
site may change the transition properties at other sites. We study the case of
escape from a "quiescent" attractor to an "active" attractor in which transitions
back can be ignored. There are qualitatively different regimes of transition,
depending on coupling strength. For small coupling strengths, the transition
rates are simply modified but the transitions remain stochastic. For large
coupling strengths, transitions happen approximately in synchrony-we call this a
"fast domino" regime. There is also an intermediate coupling regime where some
transitions happen inexorably but with a delay that may be arbitrarily long-we
call this a "slow domino" regime. We characterize these regimes in the low noise
limit in terms of bifurcations of the potential landscape of a coupled system. We
demonstrate the effect of the coupling on the distribution of timings and (in
general) the sequences of escapes of the system.
PMID- 29347648
TI - Nonreciprocal wave transmission through an extended discrete nonlinear
Schrodinger dimer.
AB - We analyze a one-dimensional extended discrete nonlinear Schrodinger (DNLS) dimer
model for nonreciprocal wave transmission. The extension corresponds to the
addition of a nonlocal or intersite nonlinear response in addition to a purely
cubic local (on-site) nonlinear response, which refines the purely cubic model
and aligns to more realistic situations. We observe that a diodelike action
persists in the extended case; however, the inclusion of nonlocal response tends
to reduce the diode action. We show that this extension results in achieving the
diode effect at lower incoming intensities as compared to the purely cubic case.
We also report that a nearly perfect diode action is possible in the extended
case for a higher level of asymmetry between on-site potentials than its cubic
counterpart. Moreover, we vary different site-dependent parameters to probe for
regimes of a better diode effect within this extended model. We also present the
corresponding stability analysis for the exact stationary solutions to the
extended DNLS equation, we discuss the bifurcation behavior in detail, and we
explicitly give the regions of stability.
PMID- 29347649
TI - Pressure and flow of exponentially self-correlated active particles.
AB - Microscopic swimming particles, which dissipate energy to execute persistent
directed motion, are a classic example of a nonequilibrium system. We investigate
the noninteracting Ornstein-Uhlenbeck Particle (OUP), which is propelled through
a viscous medium by a force which is correlated over a finite time. We obtain an
exact expression for the steady-state phase-space density of a single OUP
confined by a quadratic potential, and use the result to explore more complex
geometries, both through analytical approximations and numerical simulations. In
a "Casimir"-style setup involving two narrowly spaced walls, we describe a
particle-trapping phenomenon, which leads to a repulsive effective interaction
between the walls, while in a two-dimensional annulus geometry, we observe net
stresses which resemble the Laplace pressure.
PMID- 29347650
TI - Kinetics and thermodynamics of a driven open quantum system.
AB - Redfield theory provides a closed kinetic description of a quantum system in weak
contact with a very dense reservoir. Landau-Zener theory does the same for a time
dependent driven system in contact with a sparse reservoir. Using a simple model,
we analyze the validity of these two theories by comparing their predictions with
exact numerical results. We show that despite their a priori different range of
validity, these two descriptions can give rise to an identical quantum master
equation. Both theories can be used for a nonequilibrium thermodynamic
description, which we show is consistent with exact thermodynamic identities
evaluated in the full system-reservoir space. We emphasize the importance of
properly accounting for the system-reservoir interaction energy and of operating
in regimes where the reservoir can be considered as close to ideal.
PMID- 29347651
TI - Nonlinear and subharmonic stability analysis in film-driven morphological
patterns.
AB - The interaction of a gravity-driven water film with an evolving solid substrate
(calcite or ice) results in the formation of fascinating wavy patterns similar
both in caves and in ice-falls. Due to their remarkable similarity, we adopt a
unified approach in the study of pattern formation of longitudinally oriented
organ-pipe-like structures, called flutings. Since the morphogenesis of cave
patterns can evolve for millennia, they have an additional value as silent
repositories of past climates. Fluting formation is studied with the aid of
gradient expansion and center manifold projection. In particular, through
gradient expansion, a Benney-type equation accounting for the movable boundary is
obtained. The coupling with a wall evolution equation provides a morphodynamic
model for fluting formation, explored through linear and nonlinear analyses. In
this way, closed relationships for the selected wave number and for the finite
amplitude are achieved. However, as finite-amplitude monochromatic waves may be
destabilized by nonlinear interactions with other modes, we verify, through
center manifold projection, the stability of the fundamental to subharmonic
disturbances. Conclusively, we perform numerical simulations of the fully
nonlinear equations to validate the theory results.
PMID- 29347652
TI - Role of red cells and plasma composition on blood sessile droplet evaporation.
AB - The morphology of dried blood droplets derives from the deposition of red cells,
the main components of their solute phase. Up to now, evaporation-induced
convective flows were supposed to be at the base of red cell distribution in
blood samples. Here, we present a direct visualization by videomicroscopy of the
internal dynamics in desiccating blood droplets, focusing on the role of cell
concentration and plasma composition. We show that in diluted suspensions, the
convection is promoted by the rich molecular composition of plasma, whereas it is
replaced by an outward red blood cell displacement front at higher hematocrits.
We also evaluate by ultrasounds the effect of red cell deposition on the temporal
evolution of sample rigidity and adhesiveness.
PMID- 29347653
TI - Stochastic thermodynamics of quantum maps with and without equilibrium.
AB - We study stochastic thermodynamics for a quantum system of interest whose
dynamics is described by a completely positive trace-preserving (CPTP) map as a
result of its interaction with a thermal bath. We define CPTP maps with
equilibrium as CPTP maps with an invariant state such that the entropy production
due to the action of the map on the invariant state vanishes. Thermal maps are a
subgroup of CPTP maps with equilibrium. In general, for CPTP maps, the
thermodynamic quantities, such as the entropy production or work performed on the
system, depend on the combined state of the system plus its environment. We show
that these quantities can be written in terms of system properties for maps with
equilibrium. The relations that we obtain are valid for arbitrary coupling
strengths between the system and the thermal bath. The fluctuations of
thermodynamic quantities are considered in the framework of a two-point
measurement scheme. We derive the entropy production fluctuation theorem for
general maps and a fluctuation relation for the stochastic work on a system that
starts in the Gibbs state. Some simplifications for the probability distributions
in the case of maps with equilibrium are presented. We illustrate our results by
considering spin 1/2 systems under thermal maps, nonthermal maps with
equilibrium, maps with nonequilibrium steady states, and concatenations of them.
Finally, and as an important application, we consider a particular limit in which
the concatenation of maps generates a continuous time evolution in Lindblad form
for the system of interest, and we show that the concept of maps with and without
equilibrium translates into Lindblad equations with and without quantum detailed
balance, respectively. The consequences for the thermodynamic quantities in this
limit are discussed.
PMID- 29347654
TI - Time-dependent Tonks-Langmuir model is unstable.
AB - We investigate a time-dependent extension of the Tonks-Langmuir model for a one
dimensional plasma discharge with collisionless kinetic ions and Boltzmann
electrons. Ions are created uniformly throughout the volume and flow from the
center of the discharge to the boundary wall due to a self-consistent, zero-order
electric field. Solving this model using a particle-in-cell simulation, we
observe coherent low-frequency, long-wavelength unstable ion waves which move
toward the boundary with a speed below both the ion acoustic speed and the
average ion velocity. The maximum amplitude of the wave potential fluctuations
peaks at ~0.09T_{e} near the wall, where T_{e} is the electron temperature in
electron volts. Using linear kinetic theory, we identify this instability as slow
ion-acoustic wave modes which are destabilized by the zero-order electric field.
PMID- 29347655
TI - Emergence of chaos in a viscous solution of rods.
AB - It is shown that the addition of small amounts of microscopic rods in a viscous
fluid at low Reynolds number causes a significant increase of the flow
resistance. Numerical simulations of the dynamics of the solution reveal that
this phenomenon is associated to a transition from laminar to chaotic flow.
Polymer stresses give rise to flow instabilities which, in turn, perturb the
alignment of the rods. This coupled dynamics results in the activation of a wide
range of scales, which enhances the mixing efficiency of viscous flows.
PMID- 29347656
TI - Theory-based design of sintered granular composites triples three-phase boundary
in fuel cells.
AB - Solid-oxide fuel cells produce electric current from energy released by a
spontaneous electrochemical reaction. The efficiency of these devices depends
crucially on the microstructure of their electrodes and in particular on the
three-phase boundary (TPB) length, along which the energy-producing reaction
occurs. We present a systematic maximization of the TPB length as a function of
four readily controllable microstructural parameters, for any given mean
hydraulic radius, which is a conventional measure of the permeability to gas
flow. We identify the maximizing parameters and show that the TPB length can be
increased by a factor of over 300% compared to current common practices. We
support this result by calculating the TPB of several numerically simulated
structures. We also compare four models for a single intergranular contact in the
sintered electrode and show that the model commonly used in the literature is
oversimplified and unphysical. We then propose two alternatives.
PMID- 29347657
TI - Mapping of the Bak, Tang, and Wiesenfeld sandpile model on a two-dimensional
Ising-correlated percolation lattice to the two-dimensional self-avoiding random
walk.
AB - The self-organized criticality on the random fractal networks has many
motivations, like the movement pattern of fluid in the porous media. In addition
to the randomness, introducing correlation between the neighboring portions of
the porous media has some nontrivial effects. In this paper, we consider the
Ising-like interactions between the active sites as the simplest method to bring
correlations in the porous media, and we investigate the statistics of the BTW
model in it. These correlations are controlled by the artificial "temperature" T
and the sign of the Ising coupling. Based on our numerical results, we propose
that at the Ising critical temperature T_{c} the model is compatible with the
universality class of two-dimensional (2D) self-avoiding walk (SAW). Especially
the fractal dimension of the loops, which are defined as the external frontier of
the avalanches, is very close to D_{f}^{SAW}=4/3. Also, the corresponding open
curves has conformal invariance with the root-mean-square distance
R_{rms}~t^{3/4} (t being the parametrization of the curve) in accordance with the
2D SAW. In the finite-size study, we observe that at T=T_{c} the model has some
aspects compatible with the 2D BTW model (e.g., the 1/log(L)-dependence of the
exponents of the distribution functions) and some in accordance with the Ising
model (e.g., the 1/L-dependence of the fractal dimensions). The finite-size
scaling theory is tested and shown to be fulfilled for all statistical
observables in T=T_{c}. In the off-critical temperatures in the close vicinity of
T_{c} the exponents show some additional power-law behaviors in terms of T-T_{c}
with some exponents that are reported in the text. The spanning cluster
probability at the critical temperature also scales with L^{1/2}, which is
different from the regular 2D BTW model.
PMID- 29347658
TI - Finding multiple core-periphery pairs in networks.
AB - With a core-periphery structure of networks, core nodes are densely
interconnected, peripheral nodes are connected to core nodes to different
extents, and peripheral nodes are sparsely interconnected. Core-periphery
structure composed of a single core and periphery has been identified for various
networks. However, analogous to the observation that many empirical networks are
composed of densely interconnected groups of nodes, i.e., communities, a network
may be better regarded as a collection of multiple cores and peripheries. We
propose a scalable algorithm to detect multiple nonoverlapping groups of core
periphery structure in a network. We illustrate our algorithm using synthesized
and empirical networks. For example, we find distinct core-periphery pairs with
different political leanings in a network of political blogs and separation
between international and domestic subnetworks of airports in some single
countries in a worldwide airport network.
PMID- 29347659
TI - Crystallization of finite-extensible nonlinear elastic Lennard-Jones coarse
grained polymers.
AB - The ability of a simple coarse-grained finite-extensible nonlinear elastic (FENE)
Lennard-Jones (LJ) polymer model to be crystallized is investigated by molecular
dynamics simulations. The optimal FENE Lennard-Jones parameter combinations
(ratio between FENE and LJ equilibrium distances) and the optimal lattice
parameters are calculated for five different perfect crystallite structures:
simple tetragonal, body-centered tetragonal, body-centered orthorhombic,
hexagonal primitive, and hexagonal close packed. It was found that the most
energetically favorable structure is the body-centered orthorhombic. Starting
with an equilibrated polymer liquid and with the optimal parameters found for the
body-centered orthorhombic, an isothermal treatment led to the formation of large
lamellar crystallites with a typical chain topology: folded, loop, and tie
chains, and with a crystallinity of about 60%-70%, similar to real
semicrystalline polymers. This simple coarse-grained Lennard-Jones model provides
a qualitative tool to study semicrystalline microstructures for polymers.
PMID- 29347660
TI - Universal Gaussian behavior of driven lattice gases at short times.
AB - The dynamic and static critical behaviors of driven and equilibrium lattice gas
models are studied in two spatial dimensions. We show that in the short-time
regime immediately following a critical quench, the dynamics of the transverse
anisotropic order parameter, its autocorrelation, and Binder cumulant are
consistent with the prediction of a Gaussian, i.e., noninteracting, effective
theory, both for the nonequilibrium lattice gases and, to some extent, their
equilibrium counterpart. Such a superuniversal behavior is observed only at short
times after a critical quench, while the various models display their distinct
behaviors in the stationary states, described by the corresponding, known
universality classes.
PMID- 29347661
TI - Activity-driven changes in the mechanical properties of fire ant aggregations.
AB - Fire ant aggregations are active materials composed of individual constituents
that are able to transform internal energy into work. We find using rheology and
direct visualization that the aggregation undergoes activity cycles that affect
the mechanical properties of the system. When the activity is high, the
aggregation approximately equally stores and dissipates energy, it is more
homogeneous, and exerts a high outward force. When the activity is low, the
aggregation is predominantly elastic, it is more heterogeneous, and it exerts a
small outward force. We rationalize our results using a simple kinetic model
where the number of active ants within the aggregation is the essential quantity.
PMID- 29347662
TI - Deciphering the kinetic structure of multi-ion plasma shocks.
AB - Strong collisional shocks in multi-ion plasmas are featured in many high-energy
density environments, including inertial confinement fusion implosions. However,
their basic structure and its dependence on key parameters (e.g., the Mach number
and the plasma ion composition) are poorly understood, and inconsistencies in
that regard remain in the literature. In particular, the shock width's dependence
on the Mach number has been hotly debated for decades. Using a high-fidelity
Vlasov-Fokker-Planck code, iFP, and direct comparisons to multi-ion hydrodynamic
simulations and semianalytic predictions, we resolve the structure of steady
state planar shocks in D-^{3}He plasmas. Additionally, we derive and confirm with
kinetic simulations a quantitative description of the dependence of the shock
width on the Mach number and initial ion concentration.
PMID- 29347663
TI - Magnetization plateau as a result of the uniform and gradual electron doping in a
coupled spin-electron double-tetrahedral chain.
AB - The double-tetrahedral chain in a longitudinal magnetic field, whose nodal
lattice sites occupied by the localized Ising spins regularly alternate with
triangular plaquettes with the dynamics described by the Hubbard model, is
rigorously investigated. It is demonstrated that the uniform change of electron
concentration controlled by the chemical potential in a combination with the
competition between model parameters and the external magnetic field leads to the
formation of one chiral and seven nonchiral phases at the absolute zero
temperature. Rational plateaux at one-third and one-half of the saturation
magnetization can also be identified in the low-temperature magnetization curves.
On the other hand, the gradual electron doping results in 11 different ground
state regions that distinguish from each other by the evolution of the electron
distribution during this process. Several doping-dependent magnetization plateaux
are observed in the magnetization process as a result of the continuous change of
electron content in the model.
PMID- 29347664
TI - Morphodynamics of a growing microbial colony driven by cell death.
AB - Bacterial cells can often self-organize into multicellular structures with
complex spatiotemporal morphology. In this work, we study the spatiotemporal
dynamics of a growing microbial colony in the presence of cell death. We present
an individual-based model of nonmotile bacterial cells which grow and proliferate
by consuming diffusing nutrients on a semisolid two-dimensional surface. The
colony spreads by growth forces and sliding motility of cells and undergoes cell
death followed by subsequent disintegration of the dead cells in the medium. We
model cell death by considering two possible situations: In one of the cases,
cell death occurs in response to the limitation of local nutrients, while the
other case corresponds to an active death process, known as apoptotic or
programmed cell death. We demonstrate how the colony morphology is influenced by
the presence of cell death. Our results show that cell death facilitates
transitions from roughly circular to highly branched structures at the periphery
of an expanding colony. Interestingly, our results also reveal that for the
colonies which are growing in higher initial nutrient concentrations, cell death
occurs much earlier compared to the colonies which are growing in lower initial
nutrient concentrations. This work provides new insights into the branched
patterning of growing bacterial colonies as a consequence of complex interplay
among the biochemical and mechanical effects.
PMID- 29347665
TI - Universal features of cluster numbers in percolation.
AB - The number of clusters per site n(p) in percolation at the critical point p=p_{c}
is not itself a universal quantity; it depends upon the lattice and percolation
type (site or bond). However, many of its properties, including finite-size
corrections, scaling behavior with p, and amplitude ratios, show various degrees
of universal behavior. Some of these are universal in the sense that the behavior
depends upon the shape of the system, but not lattice type. Here, we elucidate
the various levels of universality for elements of n(p) both theoretically and by
carrying out extensive studies on several two- and three-dimensional systems, by
high-order series analysis, Monte Carlo simulation, and exact enumeration. We
find many results, including precise values for n(p_{c}) for several systems, a
clear demonstration of the singularity in n^{''}(p), and metric scale factors. We
make use of the matching polynomial of Sykes and Essam to find exact relations
between properties for lattices and matching lattices. We propose a criterion for
an absolute metric factor b based upon the singular behavior of the scaling
function, rather than a relative definition of the metric that has previously
been used.
PMID- 29347666
TI - Publisher's Note: Metal nanospheres under intense continuous-wave illumination: A
unique case of nonperturbative nonlinear nanophotonics [Phys. Rev. E 96, 012212
(2017)].
AB - This corrects the article DOI: 10.1103/PhysRevE.96.012212.
PMID- 29347667
TI - Minimal model of directed cell motility on patterned substrates.
AB - Crawling cell motility is vital to many biological processes such as wound
healing and the immune response. Using a minimal model we investigate the effects
of patterned substrate adhesiveness and biophysical cell parameters on the
direction of cell motion. We show that cells with low adhesion site formation
rates may move perpendicular to adhesive stripes while those with high adhesion
site formation rates results in motility only parallel to the substrate stripes.
We explore the effects of varying the substrate pattern geometry and the strength
of actin polymerization on the directionality of the crawling cell. These results
reveal that high strength of actin polymerization results in motion perpendicular
to substrate stripes only when the substrate is relatively nonadhesive; in
particular, this suggests potential applications in motile cell sorting and
guiding on engineered substrates.
PMID- 29347668
TI - Enabling the self-contained refrigerator to work beyond its limits by filtering
the reservoirs.
AB - In this paper, we study the quantum self-contained refrigerator [Linden et al.,
Phys. Rev. Lett. 105, 130401 (2010)PRLTAO0031-900710.1103/PhysRevLett.105.130401]
in the strong internal coupling regime with engineered reservoirs. We find that
if some modes of the three thermal reservoirs can be properly filtered out, the
efficiency and the working domain of the refrigerator can be improved in contrast
to the those in the weak internal coupling regime, which indicates one advantage
of the strong internal coupling. In addition, we find that the background natural
vacuum reservoir could cause the filtered refrigerator to stop working and the
background natural thermal reservoir could greatly reduce the cooling efficiency.
PMID- 29347669
TI - Reply to "Comment on 'Troublesome aspects of the Renyi-MaxEnt treatment' ".
AB - This Reply is intended as a refutation of the preceding Comment [Oikonomou and
Bagci, Phys. Rev. E 96, 056101 (2017)10.1103/PhysRevE.96.056101] on our paper
[Plastino et al., Phys. Rev. E 94, 012145 (2016).1539
375510.1103/PhysRevE.94.012145]. We show that the Tsallis probability
distribution of our paper does not coincide with the Tsallis distribution studied
by Oikonomou and Bagci. Consequently, their findings do not apply to our paper.
PMID- 29347670
TI - Comment on "Troublesome aspects of the Renyi-MaxEnt treatment".
AB - Plastino et al. [Plastino et al., Phys. Rev. E 94, 012145 (2016)1539
375510.1103/PhysRevE.94.012145] recently stated that the Renyi entropy is not
suitable for thermodynamics by using functional calculus, since it leads to
anomalous results unlike the Tsallis entropy. We first show that the Tsallis
entropy also leads to such anomalous behaviors if one adopts the same functional
calculus approach. Second, we note that one of the Lagrange multipliers is set in
an ad hoc manner in the functional calculus approach of Plastino et al. Finally,
the explanation for these anomalous behaviors is provided by observing that the
generalized distributions obtained by Plastino et al. do not yield the ordinary
canonical partition function in the appropriate limit and therefore cannot be
considered as genuine generalized distributions.
PMID- 29347671
TI - Kinetic-contact-driven gigantic energy transfer in a two-dimensional Lennard
Jones fluid confined to a rotating pore.
AB - A two-dimensional Lennard-Jones system in a circular and rotating container has
been studied by means of molecular dynamics technique. A nonequilibrium
transition to the rotating stage has been detected in a delayed time since an
instant switching of the frame rotation. This transition is attributed to the
increase of the density at the wall because of the centrifugal force. At the same
time the phase transition occurs, the inner system changes its configuration of
the solid-state type into the liquid type. Impact of angular frequency and
molecular roughness on the transport properties of the nonrotating and rotating
systems is analyzed.
PMID- 29347672
TI - Unified mean-field framework for susceptible-infected-susceptible epidemics on
networks, based on graph partitioning and the isoperimetric inequality.
AB - We propose an approximation framework that unifies and generalizes a number of
existing mean-field approximation methods for the susceptible-infected
susceptible (SIS) epidemic model on complex networks. We derive the framework,
which we call the unified mean-field framework (UMFF), as a set of approximations
of the exact Markovian SIS equations. Our main novelty is that we describe the
mean-field approximations from the perspective of the isoperimetric problem,
which results in bounds on the UMFF approximation error. These new bounds provide
insight in the accuracy of existing mean-field methods, such as the N-intertwined
mean-field approximation and heterogeneous mean-field method, which are contained
by UMFF. Additionally, the isoperimetric inequality relates the UMFF
approximation accuracy to the regularity notions of Szemeredi's regularity lemma.
PMID- 29347673
TI - Response and correlation functions of nonlinear systems in equilibrium states.
AB - In this paper, we study systematically a serial of correlation functions in some
one-dimensional nonlinear lattices. Due to the energy conservation law, they are
implicitly interdependent. Various transport coefficients are thus also
connected. In the studies of the autocorrelations of local energy density and of
local heat current, a general relation between diverging heat conduction and
super heat diffusion has been proposed recently. We clarify that such a relation
is valid only in systems without temperature pressure. In those with temperature
pressure, a constant but nontrivial term appears. This term explains a previously
observed fact that heat diffusion in such systems is always ballistic but heat
conduction can diverge very slowly. Such a result not only disproves the
existence of any general relation between diverging heat conduction and super
heat diffusion, but it also breaks the long-term presumption that ballistic heat
conduction and diffusion always coexist.
PMID- 29347674
TI - Alternative derivation of exact law for compressible and isothermal
magnetohydrodynamics turbulence.
AB - The exact law for fully developed homogeneous compressible magnetohydrodynamics
(CMHD) turbulence is derived. For an isothermal plasma, without the assumption of
isotropy, the exact law is expressed as a function of the plasma velocity field,
the compressible Alfven velocity, and the scalar density, instead of the Elsasser
variables used in previous works. The theoretical results show four different
types of terms that are involved in the nonlinear cascade of the total energy in
the inertial range. Each category is examined in detail, in particular, those
that can be written either as source or flux terms. Finally, the role of the
background magnetic field B_{0} is highlighted and a comparison with the
incompressible MHD (IMHD) model is discussed. This point is particularly
important when testing this exact law on numerical simulations and in situ
observations in space plasmas.
PMID- 29347675
TI - Persistent Sinai-type diffusion in Gaussian random potentials with decaying
spatial correlations.
AB - Logarithmic or Sinai-type subdiffusion is usually associated with random force
disorder and nonstationary potential fluctuations whose root-mean-squared
amplitude grows with distance. We show here that extremely persistent,
macroscopic logarithmic diffusion also universally emerges at sufficiently low
temperatures in stationary Gaussian random potentials with spatially decaying
correlations, known to exist in a broad range of physical systems. Combining
results from extensive simulations with a scaling approach we elucidate the
physical mechanism of this unusual subdiffusion. In particular, we explain why
with growing temperature and/or time a first crossover occurs to standard, power
law subdiffusion, with a time-dependent power-law exponent, and then a second
crossover occurs to normal diffusion with a disorder-renormalized diffusion
coefficient. Interestingly, the initial, nominally ultraslow diffusion turns out
to be much faster than the universal de Gennes-Bassler-Zwanzig limit of the
renormalized normal diffusion, which realistically cannot be attained at
sufficiently low temperatures and/or for strong disorder. The ultraslow diffusion
is also shown to be nonergodic and it displays a local bias phenomenon. Our
simple scaling theory not only explains our numerical findings but qualitatively
also has a predictive character.
PMID- 29347676
TI - Twitching motility of bacteria with type-IV pili: Fractal walks, first passage
time, and their consequences on microcolonies.
AB - A human pathogen, Neisseria gonorrhoeae (NG), moves on surfaces by attaching and
retracting polymeric structures called Type IV pili. The tug-of-war between the
pili results in a two-dimensional stochastic motion called twitching motility. In
this paper, with the help of real-time NG trajectories, we develop coarse-grained
models for their description. The fractal properties of these trajectories are
determined and their influence on first passage time and formation of bacterial
microcolonies is studied. Our main observations are as follows: (i) NG performs a
fast ballistic walk on small time scales and a slow diffusive walk over long time
scales with a long crossover region; (ii) there exists a characteristic
persistent length l_{p}^{*}, which yields the fastest growth of bacterial
aggregates or biofilms. Our simulations reveal that l_{p}^{*}~L^{0.6}, where L*L
is the surface on which the bacteria move; (iii) the morphologies have distinct
fractal characteristics as a consequence of the ballistic and diffusive motion of
the constituting bacteria.
PMID- 29347677
TI - Sidewall-friction-driven ordering transition in granular channel flows:
Implications for granular rheology.
AB - We report a transition from a disordered state to an ordered state in the flow of
nearly monodisperse granular matter flowing in an inclined channel with planar
slide walls and a bumpy base, using discrete element method simulations. For low
particle-sidewall friction coefficients, the flowing particles are disordered,
however, for high sidewall friction, an ordered state is obtained, characterized
by a layering of the particles and hexagonal packing of the particles in each
layer. The extent of ordering, quantified by the local bond-orientational order
parameter, varies in the cross section of the channel, with the highest ordering
near the sidewalls. The flow transition significantly affects the local rheology
the effective friction coefficient is lower, and the packing fraction is higher,
in the ordered state compared to the disordered state. A simple model,
incorporating the extent of local ordering, is shown to describe the rheology of
the system.
PMID- 29347678
TI - Detection of transition times from single-particle-tracking trajectories.
AB - In heterogeneous environments, the diffusivity is not constant but changes with
time. It is important to detect changes in the diffusivity from single-particle
tracking trajectories in experiments. Here, we devise a novel method for
detecting the transition times of the diffusivity from trajectory data. A key
idea of this method is the introduction of a characteristic time scale of the
diffusive states, which is obtained by a fluctuation analysis of the time
averaged mean square displacements. We test our method in silico by using the
Langevin equation with a fluctuating diffusivity. We show that our method can
successfully detect the transition times of diffusive states and obtain the
diffusion coefficient as a function of time. This method will provide a
quantitative description of the fluctuating diffusivity in heterogeneous
environments and can be applied to time series with transitions of states.
PMID- 29347679
TI - Pathways to equilibrium orientation fluctuations in finite stripe-forming
systems.
AB - Small-angle orientation fluctuations in ordered stripe-forming systems free of
topological defects can exhibit aging and anisotropic growth of two length
scales. In infinitely extended systems, the stripe orientation field develops a
dominant modulation length lambda_{?}^{*}(t) in the direction parallel to the
stripes, which increases with time t as lambda_{?}^{*}(t)~t^{1/4}.
Simultaneously, the orientation correlation length xi_{?}(t) in the direction
perpendicular to the stripes increases as xi_{?}(t)~t^{1/2} [Riesch et al.,
Interface Focus 7, 20160146 (2017)2042-889810.1098/rsfs.2016.0146]. Here we show
that finite systems of size L_{?}*L_{?} with periodic boundary conditions reach
equilibrium when the dominant modulation length lambda_{?}^{*}(t) reaches the
system size L_{?} in the stripe direction. The equilibration time tau_{eq}^{?} is
solely determined by L_{?}, with tau_{eq}^{?}~L_{?}^{4}. In systems with
L_{?}GUE, P->GOE, and GOE->GUE with the results from random matrix
theory, we prove that these crossovers are described reasonably. Recent
investigations by F. Schweiner et al. [Phys. Rev. E 95, 062205 (2017)2470
004510.1103/PhysRevE.95.062205] have shown that the Hamiltonian of
magnetoexcitons in cubic semiconductors can exhibit all three statistics in
dependence on the system parameters. Evaluating the numerical results for
magnetoexcitons in dependence on the excitation energy and on a parameter
connected with the cubic valence band structure and comparing the results with
the formula proposed allows us to distinguish between regular and chaotic
behavior as well as between existent or broken antiunitary symmetries. Increasing
one of the two parameters, transitions between different crossovers, e.g., from
the P->GOE to the P->GUE crossover, are observed and discussed.
PMID- 29347684
TI - Scalable and fast heterogeneous molecular simulation with predictive
parallelization schemes.
AB - Multiscale and inhomogeneous molecular systems are challenging topics in the
field of molecular simulation. In particular, modeling biological systems in the
context of multiscale simulations and exploring material properties are driving a
permanent development of new simulation methods and optimization algorithms. In
computational terms, those methods require parallelization schemes that make a
productive use of computational resources for each simulation and from its
genesis. Here, we introduce the heterogeneous domain decomposition approach,
which is a combination of an heterogeneity-sensitive spatial domain decomposition
with an a priori rearrangement of subdomain walls. Within this approach, the
theoretical modeling and scaling laws for the force computation time are proposed
and studied as a function of the number of particles and the spatial resolution
ratio. We also show the new approach capabilities, by comparing it to both static
domain decomposition algorithms and dynamic load-balancing schemes. Specifically,
two representative molecular systems have been simulated and compared to the
heterogeneous domain decomposition proposed in this work. These two systems
comprise an adaptive resolution simulation of a biomolecule solvated in water and
a phase-separated binary Lennard-Jones fluid.
PMID- 29347685
TI - Statistical independence of the initial conditions in chaotic mixing.
AB - Experimental evidence of the scalar convergence towards a global strange
eigenmode independent of the scalar initial condition in chaotic mixing is
provided. This convergence, underpinning the independent nature of chaotic mixing
in any passive scalar, is presented by scalar fields with different initial
conditions casting statistically similar shapes when advected by periodic
unsteady flows. As the scalar patterns converge towards a global strange
eigenmode, the scalar filaments, locally aligned with the direction of maximum
stretching, as described by the Lagrangian stretching theory, stack together in
an inhomogeneous pattern at distances smaller than their asymptotic minimum
widths. The scalar variance decay becomes then exponential and independent of the
scalar diffusivity or initial condition. In this work, mixing is achieved by
advecting the scalar using a set of laminar flows with unsteady periodic
topology. These flows, that resemble the tendril-whorl map, are obtained by
morphing the forcing geometry in an electromagnetic free surface 2D mixing
experiment. This forcing generates a velocity field which periodically switches
between two concentric hyperbolic and elliptic stagnation points. In agreement
with previous literature, the velocity fields obtained produce a chaotic mixer
with two regions: a central mixing and an external extensional area. These two
regions are interconnected through two pairs of fluid conduits which transfer
clean and dyed fluid from the extensional area towards the mixing region and a
homogenized mixture from the mixing area towards the extensional region.
PMID- 29347686
TI - Geometric phaselike effects in a quantum heat engine.
AB - By periodically driving the temperature of reservoirs in a quantum heat engine,
geometric or Pancharatnam-Berry phaselike (PBp) effects in the thermodynamics can
be observed. The PBp can be identified from a generating function (GF) method
within an adiabatic quantum Markovian master equation formalism. The GF is shown
not to lead to a standard open quantum system's fluctuation theorem in the
presence of phase-different modulations with an inapplicability in the use of
large deviation theory. Effect of quantum coherences in optimizing the flux is
nullified due to PBp contributions. The linear coefficient, 1/2, which is
universal in the expansion of the efficiency at maximum power in terms of Carnot
efficiency no longer holds true in the presence of PBp effects.
PMID- 29347687
TI - Corrected simulations for one-dimensional diffusion processes with naturally
occurring boundaries.
AB - To simulate a diffusion process, a usual approach is to discretize the time in
the associated stochastic differential equation. This is the approach used in the
Euler method. In the present work we consider a one-dimensional diffusion process
where the terms occurring, within the stochastic differential equation, prevent
the process entering a region. The outcome is a naturally occurring boundary
(which may be absorbing or reflecting). A complication occurs in a simulation of
this situation. The term involving a random variable, within the discretized
stochastic differential equation, may take a trajectory across the boundary into
a "forbidden region." The naive way of dealing with this problem, which we refer
to as the "standard" approach, is simply to reset the trajectory to the boundary,
based on the argument that crossing the boundary actually signifies achieving the
boundary. In this work we show, within the framework of the Euler method, that
such resetting introduces a spurious force into the original diffusion process.
This force may have a significant influence on trajectories that come close to a
boundary. We propose a corrected numerical scheme, for simulating one-dimensional
diffusion processes with naturally occurring boundaries. This involves correcting
the standard approach, so that an exact property of the diffusion process is
precisely respected. As a consequence, the proposed scheme does not introduce a
spurious force into the dynamics. We present numerical test cases, based on
exactly soluble one-dimensional problems with one or two boundaries, which
suggest that, for a given value of the discrete time step, the proposed scheme
leads to substantially more accurate results than the standard approach.
Alternatively, the standard approach needs considerably more computation time to
obtain a comparable level of accuracy to the proposed scheme, because the
standard approach requires a significantly smaller time step.
PMID- 29347688
TI - Infection dynamics on spatial small-world network models.
AB - The study of complex networks, and in particular of social networks, has mostly
concentrated on relational networks, abstracting the distance between nodes.
Spatial networks are, however, extremely relevant in our daily lives, and a large
body of research exists to show that the distances between nodes greatly
influence the cost and probability of establishing and maintaining a link. A
random geometric graph (RGG) is the main type of synthetic network model used to
mimic the statistical properties and behavior of many social networks. We propose
a model, called REDS, that extends energy-constrained RGGs to account for the
synergic effect of sharing the cost of a link with our neighbors, as is observed
in real relational networks. We apply both the standard Watts-Strogatz rewiring
procedure and another method that conserves the degree distribution of the
network. The second technique was developed to eliminate unwanted forms of
spatial correlation between the degree of nodes that are affected by rewiring,
limiting the effect on other properties such as clustering and assortativity. We
analyze both the statistical properties of these two network types and their
epidemiological behavior when used as a substrate for a standard susceptible
infected-susceptible compartmental model. We consider and discuss the differences
in properties and behavior between RGGs and REDS as rewiring increases and as
infection parameters are changed. We report considerable differences both between
the network types and, in the case of REDS, between the two rewiring schemes. We
conclude that REDS represent, with the application of these rewiring mechanisms,
extremely useful and interesting tools in the study of social and epidemiological
phenomena in synthetic complex networks.
PMID- 29347689
TI - Improved locality of the phase-field lattice-Boltzmann model for immiscible
fluids at high density ratios.
AB - Based on phase-field theory, we introduce a robust lattice-Boltzmann equation for
modeling immiscible multiphase flows at large density and viscosity contrasts.
Our approach is built by modifying the method proposed by Zu and He [Phys. Rev. E
87, 043301 (2013)PLEEE81539-375510.1103/PhysRevE.87.043301] in such a way as to
improve efficiency and numerical stability. In particular, we employ a different
interface-tracking equation based on the so-called conservative phase-field
model, a simplified equilibrium distribution that decouples pressure and velocity
calculations, and a local scheme based on the hydrodynamic distribution functions
for calculation of the stress tensor. In addition to two distribution functions
for interface tracking and recovery of hydrodynamic properties, the only nonlocal
variable in the proposed model is the phase field. Moreover, within our framework
there is no need to use biased or mixed difference stencils for numerical
stability and accuracy at high density ratios. This not only simplifies the
implementation and efficiency of the model, but also leads to a model that is
better suited to parallel implementation on distributed-memory machines. Several
benchmark cases are considered to assess the efficacy of the proposed model,
including the layered Poiseuille flow in a rectangular channel, Rayleigh-Taylor
instability, and the rise of a Taylor bubble in a duct. The numerical results are
in good agreement with available numerical and experimental data.
PMID- 29347690
TI - Inherent stress correlations in a quiescent two-dimensional liquid: Static
analysis including finite-size effects.
AB - After constructing a formalism to analyze spatial stress correlations in two
dimensional equilibrated liquids, we show that the sole conjunction of mechanical
balance and material isotropy demands all anisotropic components of the inherent
state (IS) stress autocorrelation matrix to decay at long range as 1/r^{2} in the
large system size limit. Furthermore, analyzing numerical simulation data for an
equilibrated supercooled liquid, we bring evidence that, in finite-sized periodic
systems, the autocorrelations of pressure and shear stresses present uniform
backgrounds of amplitudes proportional to the inverse cell area. These
backgrounds bring relevant contributions to macroscopic IS stress fluctuations,
with the consequence that the latter scale as inverse area, yet in an anomalous
way, inconsistent with viewing an IS as equivalent, in the thermodynamic limit,
to an ensemble of independent finite-sized subsystems. In that sense, ISs are not
spatially ergodic.
PMID- 29347691
TI - Dynamics of functional failures and recovery in complex road networks.
AB - We propose a new framework for modeling the evolution of functional failures and
recoveries in complex networks, with traffic congestion on road networks as the
case study. Differently from conventional approaches, we transform the evolution
of functional states into an equivalent dynamic structural process: dual-vertex
splitting and coalescing embedded within the original network structure. The
proposed model successfully explains traffic congestion and recovery patterns at
the city scale based on high-resolution data from two megacities. Numerical
analysis shows that certain network structural attributes can amplify or suppress
cascading functional failures. Our approach represents a new general framework to
model functional failures and recoveries in flow-based networks and allows
understanding of the interplay between structure and function for flow-induced
failure propagation and recovery.
PMID- 29347692
TI - Effect of the correlation between internal noise and external noise on logical
stochastic resonance in bistable systems.
AB - Some noisy nonlinear systems could be exploited to operate reliable logic
operation in an optimal window of noise intensity, which is termed as logical
stochastic resonance (LSR). We investigated the LSR phenomenon in bistable
systems when internal noise and external noise are correlated. The LSR effect is
evaluated by the success probability of the obtained desired output with various
combinations of logic inputs. It is shown that the or-nor, and-nand, and Latch
operations still can operate reliably with the correlated internal noise and
external noise. A positive correlation strength tends to enhance or-nor logic and
suppress and-nand logic. The negative correlation strength tends to suppress or
nor logic and enhance and-nand logic. The results provide possible corroboration
for implementing reliable LSR when internal noise and external noise are
correlated.
PMID- 29347693
TI - Flow instabilities due to the interfacial formation of surfactant-fatty acid
material in a Hele-Shaw cell.
AB - We present an experimental study of pattern formation during the penetration of
an aqueous surfactant solution into a liquid fatty acid in a Hele-Shaw cell. When
a solution of the cationic surfactant cetylpyridinium chloride is injected into
oleic acid, a wide variety of fingering patterns are observed as a function of
surfactant concentration and flow rate, which are strikingly different than the
classic Saffman-Taylor (ST) instability. We observe evidence of interfacial
material forming between the two liquids, causing these instabilities. Moreover,
the number of fingers decreases with increasing flow rate Q, while the average
finger width increases with Q, both trends opposite to the ST case. Bulk rheology
on related mixtures indicates a gel-like state. Comparison of experiments using
other oils indicates the importance of pH and the carboxylic head group in the
formation of the surfactant-fatty acid material.
PMID- 29347694
TI - Constraint percolation on hyperbolic lattices.
AB - Hyperbolic lattices interpolate between finite-dimensional lattices and Bethe
lattices, and they are interesting in their own right, with ordinary percolation
exhibiting not one but two phase transitions. We study four constraint
percolation models-k-core percolation (for k=1,2,3) and force-balance percolation
on several tessellations of the hyperbolic plane. By comparing these four
different models, our numerical data suggest that all of the k-core models, even
for k=3, exhibit behavior similar to ordinary percolation, while the force
balance percolation transition is discontinuous. We also provide proof, for some
hyperbolic lattices, of the existence of a critical probability that is less than
unity for the force-balance model, so that we can place our interpretation of the
numerical data for this model on a more rigorous footing. Finally, we discuss
improved numerical methods for determining the two critical probabilities on the
hyperbolic lattice for the k-core percolation models.
PMID- 29347695
TI - Optimal dephasing for ballistic energy transfer in disordered linear chains.
AB - We study the interplay between dephasing, disorder, and coupling to a sink on
transport efficiency in a one-dimensional chain of finite length N, and in
particular the beneficial or detrimental effect of dephasing on transport. The
excitation moves along the chain by coherent nearest-neighbor hopping Omega,
under the action of static disorder W and dephasing gamma. The last site is
coupled to an external acceptor system (sink), where the excitation can be
trapped with a rate Gamma_{trap}. While it is known that dephasing can help
transport in the localized regime, here we show that dephasing can enhance energy
transfer even in the ballistic regime. Specifically, in the localized regime we
recover previous results, where the optimal dephasing is independent of the chain
length and proportional to W or W^{2}/Omega. In the ballistic regime, the optimal
dephasing decreases as 1/N or 1/sqrt[N], respectively, for weak and moderate
static disorder. When focusing on the excitation starting at the beginning of the
chain, dephasing can help excitation transfer only above a critical value of
disorder W^{cr}, which strongly depends on the sink coupling strength
Gamma_{trap}. Analytic solutions are obtained for short chains.
PMID- 29347697
TI - Multichannel scattering problem with a nonseparable angular part as a boundary
value problem.
AB - We have developed an efficient computational method for solving the quantum
multichannel scattering problem with a nonseparable angular part. The use of the
nondirect product discrete-variable representation, suggested and developed by V.
Melezhik, gives us an accurate approximation for the angular part of the desired
wave function and, eventually, for the scattering parameters. Subsequent
reduction of the problem to the boundary-value problem with well-defined block
band matrix of equation coefficients permits us to use efficient standard
algorithms for its solution. We demonstrate the numerical efficiency,
flexibility, and good convergence of the computational scheme in a quantitative
description of the Feshbach resonances in pair collisions occurring in atomic
traps and the scattering in strongly anisotropic traps. The method can also be
used for the investigation of further actual problems in quantum physics. A
natural extension is a description of spin-orbit coupling, intensively
investigated in ultracold gases, and dipolar confinement-induced resonances.
PMID- 29347696
TI - Stochastic dynamics of genetic broadcasting networks.
AB - The complex genetic programs of eukaryotic cells are often regulated by key
transcription factors occupying or clearing out of a large number of genomic
locations. Orchestrating the residence times of these factors is therefore
important for the well organized functioning of a large network. The classic
models of genetic switches sidestep this timing issue by assuming the binding of
transcription factors to be governed entirely by thermodynamic protein-DNA
affinities. Here we show that relying on passive thermodynamics and random
release times can lead to a "time-scale crisis" for master genes that broadcast
their signals to a large number of binding sites. We demonstrate that this time
scale crisis for clearance in a large broadcasting network can be resolved by
actively regulating residence times through molecular stripping. We illustrate
these ideas by studying a model of the stochastic dynamics of the genetic network
of the central eukaryotic master regulator NFkappaB which broadcasts its signals
to many downstream genes that regulate immune response, apoptosis, etc.
PMID- 29347698
TI - Field dynamics inference via spectral density estimation.
AB - Stochastic differential equations are of utmost importance in various scientific
and industrial areas. They are the natural description of dynamical processes
whose precise equations of motion are either not known or too expensive to solve,
e.g., when modeling Brownian motion. In some cases, the equations governing the
dynamics of a physical system on macroscopic scales occur to be unknown since
they typically cannot be deduced from general principles. In this work, we
describe how the underlying laws of a stochastic process can be approximated by
the spectral density of the corresponding process. Furthermore, we show how the
density can be inferred from possibly very noisy and incomplete measurements of
the dynamical field. Generally, inverse problems like these can be tackled with
the help of Information Field Theory. For now, we restrict to linear and
autonomous processes. To demonstrate its applicability, we employ our
reconstruction algorithm on a time-series and spatiotemporal processes.
PMID- 29347699
TI - Dynamic scaling in the two-dimensional Ising spin glass with normal-distributed
couplings.
AB - We carry out simulated annealing and employ a generalized Kibble-Zurek scaling
hypothesis to study the two-dimensional Ising spin glass with normal-distributed
couplings. The system has an equilibrium glass transition at temperature T=0.
From a scaling analysis when T->0 at different annealing velocities v, we find
power-law scaling in the system size for the velocity required in order to relax
toward the ground state, v~L^{-(z+1/nu)}, the Kibble-Zurek ansatz where z is the
dynamic critical exponent and nu the previously known correlation-length
exponent, nu~3.6. We find z~13.6 for both the Edwards-Anderson spin-glass order
parameter and the excess energy. This is different from a previous study of the
system with bimodal couplings [Rubin et al., Phys. Rev. E 95, 052133 (2017)2470
004510.1103/PhysRevE.95.052133] where the dynamics is faster (z is smaller) and
the above two quantities relax with different dynamic exponents (with that of the
energy being larger). We argue that the different behaviors arise as a
consequence of the different low-energy landscapes: for normal-distributed
couplings the ground state is unique (up to a spin reflection), while the system
with bimodal couplings is massively degenerate. Our results reinforce the
conclusion of anomalous entropy-driven relaxation behavior in the bimodal Ising
glass. In the case of a continuous coupling distribution, our results presented
here also indicate that, although Kibble-Zurek scaling holds, the perturbative
behavior normally applying in the slow limit breaks down, likely due to
quasidegenerate states, and the scaling function takes a different form.
PMID- 29347700
TI - Numerical design of a T-shaped microfluidic device for deformability-based
separation of elastic capsules and soft beads.
AB - We propose a square cross-section microfluidic channel with an orthogonal side
branch (asymmetric T-shaped bifurcation) for the separation of elastic capsules
and soft beads suspended in a Newtonian liquid on the basis of their mechanical
properties. The design is performed through three-dimensional direct numerical
simulations. When suspended objects start near the inflow channel centerline and
the carrier fluid is equally partitioned between the two outflow branches,
particle separation can be achieved based on their deformability, with the
stiffer ones going "straight" and the softer ones being deviated to the "side"
branch. The effects of the geometrical and physical parameters of the system on
the phenomenon are investigated. Since cell deformability can be significantly
modified by pathology, we give a proof of concept on the possibility of
separating diseased cells from healthy ones, thus leading to illness diagnosis.
PMID- 29347701
TI - Speed-of-light pulses in the massless nonlinear Dirac equation with a potential.
AB - We consider the massless nonlinear Dirac (NLD) equation in 1+1 dimension with
scalar-scalar self-interaction g^{2}/2(Psi[over -]Psi)^{2} in the presence of
three external electromagnetic real potentials V(x), a potential barrier, a
constant potential, and a potential well. By solving numerically the NLD
equation, we find different scenarios depending on initial conditions, namely,
propagation of the initial pulse along one direction, splitting of the initial
pulse into two pulses traveling in opposite directions, and focusing of two
initial pulses followed by a splitting. For all considered cases, the final waves
travel with the speed of light and are solutions of the massless linear Dirac
equation. During these processes the charge and the energy are conserved, whereas
the momentum is conserved when the solutions possess specific symmetries. For the
case of the constant potential, we derive exact analytical solutions of the
massless NLD equation that are also solutions of the massless linearized Dirac
equation. Decay or growth of the initial pulse is also predicted from the
evolution of the charge for the case of a non-zero imaginary part of the
potential.
PMID- 29347702
TI - Orbitals for classical arbitrary anisotropic colloidal potentials.
AB - Coarse-grained potentials are ubiquitous in mesoscale simulations. While various
methods to compute effective interactions for spherically symmetric particles
exist, anisotropic interactions are seldom used, due to their complexity. Here we
describe a general formulation, based on a spatial decomposition of the density
fields around the particles, akin to atomic orbitals. We show that anisotropic
potentials can be efficiently computed in numerical simulations using Fourier
based methods. We validate the field formulation and characterize its
computational efficiency with a system of colloids that have Gaussian surface
charge distributions. We also investigate the phase behavior of charged Janus
colloids immersed in screened media, with screening lengths comparable to the
colloid size. The system shows rich behaviors, exhibiting vapor, liquid, gel, and
crystalline morphologies, depending on temperature and screening length. The
crystalline phase only appears for symmetric Janus particles. For very short
screening lengths, the system undergoes a direct transition from a vapor to a
crystal on cooling; while, for longer screening lengths, a vapor-liquid-crystal
transition is observed. The proposed formulation can be extended to model force
fields that are time or orientation dependent, such as those in systems of
polymer-grafted particles and magnetic colloids.
PMID- 29347703
TI - Detecting the chaotic nature in a transitional boundary layer using symbolic
information-theory quantifiers.
AB - The permutation entropy and the statistical complexity are employed to study the
boundary-layer transition induced by the surface roughness. The velocity signals
measured in the transition process are analyzed with these symbolic quantifiers,
as well as the complexity-entropy causality plane, and the chaotic nature of the
instability fluctuations is identified. The frequency of the dominant
fluctuations has been found according to the time scales corresponding to the
extreme values of the symbolic quantifiers. The laminar-turbulent transition
process is accompanied by the evolution in the degree of organization of the
complex eddy motions, which is also characterized with the growing smaller and
flatter circles in the complexity-entropy causality plane. With the help of the
permutation entropy and the statistical complexity, the differences between the
chaotic fluctuations detected in the experiments and the classical Tollmien
Schlichting wave are shown and discussed. It is also found that the chaotic
features of the instability fluctuations can be approximated with a number of
regular sine waves superimposed on the fluctuations of the undisturbed laminar
boundary layer. This result is related to the physical mechanism in the
generation of the instability fluctuations, which is the noise-induced chaos.
PMID- 29347704
TI - Recurrence due to periodic multisoliton fission in the defocusing nonlinear
Schrodinger equation.
AB - We address the degree of universality of the Fermi-Pasta-Ulam recurrence induced
by multisoliton fission from a harmonic excitation by analyzing the case of the
semiclassical defocusing nonlinear Schrodinger equation, which models nonlinear
wave propagation in a variety of physical settings. Using a suitable Wentzel
Kramers-Brillouin approach to the solution of the associated scattering problem
we accurately predict, in a fully analytical way, the number and the features
(amplitude and velocity) of solitonlike excitations emerging post-breaking, as a
function of the dispersion smallness parameter. This also permits us to predict
and analyze the near-recurrences, thereby inferring the universal character of
the mechanism originally discovered for the Korteweg-deVries equation. We show,
however, that important differences exist between the two models, arising from
the different scaling rules obeyed by the soliton velocities.
PMID- 29347705
TI - Exploring cluster Monte Carlo updates with Boltzmann machines.
AB - Boltzmann machines are physics informed generative models with broad applications
in machine learning. They model the probability distribution of an input data set
with latent variables and generate new samples accordingly. Applying the
Boltzmann machines back to physics, they are ideal recommender systems to
accelerate the Monte Carlo simulation of physical systems due to their
flexibility and effectiveness. More intriguingly, we show that the generative
sampling of the Boltzmann machines can even give different cluster Monte Carlo
algorithms. The latent representation of the Boltzmann machines can be designed
to mediate complex interactions and identify clusters of the physical system. We
demonstrate these findings with concrete examples of the classical Ising model
with and without four-spin plaquette interactions. In the future, automatic
searches in the algorithm space parametrized by Boltzmann machines may discover
more innovative Monte Carlo updates.
PMID- 29347706
TI - Oscillation collapse in coupled quantum van der Pol oscillators.
AB - The classical self-oscillations can collapse merely due to their mutual
couplings. We investigate this oscillation collapse in quantum van der Pol
oscillators. For a pair of quantum oscillators, the steady-state mean phonon
number is shown to be lower than in the corresponding classical model with a
Gaussian white noise that mimics quantum noise. We further show within the mean
field theory that a number of globally coupled oscillators undergo a transition
from the synchronized periodic motion to the collective oscillation collapse. A
quantum many-body simulation suggests that the increase in the number of
oscillators leads to a lower steady-state mean phonon number, bounded below by
the mean-field result.
PMID- 29347707
TI - Current quantization and fractal hierarchy in a driven repulsive lattice gas.
AB - Driven lattice gases are widely regarded as the paradigm of collective phenomena
out of equilibrium. While such models are usually studied with nearest-neighbor
interactions, many empirical driven systems are dominated by slowly decaying
interactions such as dipole-dipole and Van der Waals forces. Motivated by this
gap, we study the nonequilibrium stationary state of a driven lattice gas with
slow-decayed repulsive interactions at zero temperature. By numerical and
analytical calculations of the particle current as a function of the density and
of the driving field, we identify (i) an abrupt breakdown transition between
insulating and conducting states, (ii) current quantization into discrete phases
where a finite current flows with infinite differential resistivity, and (iii) a
fractal hierarchy of excitations, related to the Farey sequences of number
theory. We argue that the origin of these effects is the competition between
scales, which also causes the counterintuitive phenomenon that crystalline states
can melt by increasing the density.
PMID- 29347708
TI - Inverse Bremsstrahlung current drive.
AB - The generation of the plasma current resulting from Bremsstrahlung absorption is
considered. It is shown that the electric current is higher than the naive
estimates assuming that electrons absorb only the photon momentum and using the
Spitzer conductivity would suggest. The current enhancement is in part because
electrons get the recoil momentum from the Coulomb field of ions during the
absorption and in part because the electromagnetic power is absorbed
asymmetrically within the electron velocity distribution space.
PMID- 29347709
TI - Interaction of a planar reacting shock wave with an isotropic turbulent vorticity
field.
AB - Linear interaction analysis (LIA) is employed to investigate the interaction of
reactive and nonreactive shock waves with isotropic vortical turbulence. The
analysis is carried out, through Laplace-transform technique, accounting for long
time effects of vortical disturbances on the burnt-gas flow in the fast-reaction
limit, where the reaction-region thickness is significantly small in comparison
with the most representative turbulent length scales. Results provided by the
opposite slow-reaction limit are also recollected. The reactive case is here
restricted to situations where the overdriven detonation front does not exhibit
self-induced oscillations nor inherent instabilities. The interaction of the
planar detonation with a monochromatic pattern of perturbations is addressed
first, and then a Fourier superposition for three-dimensional isotropic turbulent
fields is employed to provide integral formulas for the amplification of the
kinetic energy, enstrophy, and anisotropy downstream. Transitory evolution is
also provided for single-frequency disturbances. In addition, further effects
associated to the reaction rate, which have not been included in LIA, are studied
through direct numerical simulations. The numerical computations, based on WENO
BO4-type scheme, provide spatial profiles of the turbulent structures downstream
for four different conditions that include nonreacting shock waves, unstable
reacting shock (sufficiently high activation energy), and stable reacting shocks
for different detonation thicknesses. Effects of the propagation Mach number,
chemical heat release, and burn rate are analyzed.
PMID- 29347710
TI - Entropic nonadditivity, H theorem, and nonlinear Klein-Kramers equations.
AB - We use the H theorem to establish the entropy and the entropic additivity law for
a system composed of subsystems, with the dynamics governed by the Klein-Kramers
equations, by considering relations among the dynamics of these subsystems and
their entropies. We start considering the subsystems governed by linear Klein
Kramers equations and verify that the Boltzmann-Gibbs entropy is appropriated to
this dynamics, leading us to the standard entropic additivity,
S_{BG}^{(1?2)}=S_{BG}^{1}+S_{BG}^{2}, consistent with the fact that the
distributions of the subsystem are independent. We then extend the dynamics of
these subsystems to independent nonlinear Klein-Kramers equations. For this case,
the results show that the H theorem is verified for a generalized entropy, which
does not preserve the standard entropic additivity for independent distributions.
In this scenario, consistent results are obtained when a suitable coupling among
the nonlinear Klein-Kramers equations is considered, in which each subsystem
modifies the other until an equilibrium state is reached. This dynamics, for the
subsystems, results in the Tsallis entropy for the system and, consequently,
verifies the relation S_{q}^{(1?2)}=S_{q}^{1}+S_{q}^{2}+(1
q)S_{q}^{1}S_{q}^{2}/k, which is a nonadditive entropic relation.
PMID- 29347711
TI - Shock-wave-like structures induced by an exothermic neutralization reaction in
miscible fluids.
AB - We report shock-wave-like structures that are strikingly different from
previously observed fingering instabilities, which occur in a two-layer system of
miscible fluids reacting by a second-order reaction A+B->S in a vertical Hele
Shaw cell. While the traditional analysis expects the occurrence of a diffusion
controlled convection, we show both experimentally and theoretically that the
exothermic neutralization reaction can also trigger a wave with a perfectly
planar front and nearly discontinuous change in density across the front. This
wave propagates fast compared with the characteristic diffusion times and
separates the motionless fluid and the area with anomalously intense convective
mixing. We explain its mechanism and introduce a new dimensionless parameter,
which allows to predict the appearance of such a pattern in other systems.
Moreover, we show that our governing equations, taken in the inviscid limit, are
formally analogous to well-known shallow-water equations and adiabatic gas flow
equations. Based on this analogy, we define the critical velocity for the onset
of the shock wave which is found to be in the perfect agreement with the
experiments.
PMID- 29347712
TI - From quenched disorder to continuous time random walk.
AB - This work focuses on quantitative representation of transport in systems with
quenched disorder. Explicit mapping of the quenched trap model to continuous time
random walk is presented. Linear temporal transformation, t->t/Lambda^{1/alpha},
for a transient process in the subdiffusive regime is sufficient for asymptotic
mapping. An exact form of the constant Lambda^{1/alpha} is established. A
disorder averaged position probability density function for a quenched trap model
is obtained, and analytic expressions for the diffusion coefficient and drift are
provided.
PMID- 29347713
TI - Discrete Boltzmann modeling of Rayleigh-Taylor instability in two-component
compressible flows.
AB - A discrete Boltzmann model (DBM) is proposed to probe the Rayleigh-Taylor
instability (RTI) in two-component compressible flows. Each species has a
flexible specific-heat ratio and is described by one discrete Boltzmann equation
(DBE). Independent discrete velocities are adopted for the two DBEs. The
collision and force terms in the DBE account for the molecular collision and
external force, respectively. Two types of force terms are exploited. In addition
to recovering the modified Navier-Stokes equations in the hydrodynamic limit, the
DBM has the capability of capturing detailed nonequilibrium effects. Furthermore,
we use the DBM to investigate the dynamic process of the RTI. The invariants of
tensors for nonequilibrium effects are presented and studied. For low Reynolds
numbers, both global nonequilibrium manifestations and the growth rate of the
entropy of mixing show three stages (i.e., the reducing, increasing, and then
decreasing trends) in the evolution of the RTI. On the other hand, the early
reducing tendency is suppressed and even eliminated for high Reynolds numbers.
Relevant physical mechanisms are analyzed and discussed.
PMID- 29347714
TI - Fluctuating hydrodynamics, current fluctuations, and hyperuniformity in boundary
driven open quantum chains.
AB - We consider a class of either fermionic or bosonic noninteracting open quantum
chains driven by dissipative interactions at the boundaries and study the
interplay of coherent transport and dissipative processes, such as bulk dephasing
and diffusion. Starting from the microscopic formulation, we show that the
dynamics on large scales can be described in terms of fluctuating hydrodynamics.
This is an important simplification as it allows us to apply the methods of
macroscopic fluctuation theory to compute the large deviation (LD) statistics of
time-integrated currents. In particular, this permits us to show that fermionic
open chains display a third-order dynamical phase transition in LD functions. We
show that this transition is manifested in a singular change in the structure of
trajectories: while typical trajectories are diffusive, rare trajectories
associated with atypical currents are ballistic and hyperuniform in their spatial
structure. We confirm these results by numerically simulating ensembles of rare
trajectories via the cloning method, and by exact numerical diagonalization of
the microscopic quantum generator.
PMID- 29347715
TI - Cusps enable line attractors for neural computation.
AB - Line attractors in neuronal networks have been suggested to be the basis of many
brain functions, such as working memory, oculomotor control, head movement,
locomotion, and sensory processing. In this paper, we make the connection between
line attractors and pulse gating in feed-forward neuronal networks. In this
context, because of their neutral stability along a one-dimensional manifold,
line attractors are associated with a time-translational invariance that allows
graded information to be propagated from one neuronal population to the next. To
understand how pulse-gating manifests itself in a high-dimensional, nonlinear,
feedforward integrate-and-fire network, we use a Fokker-Planck approach to
analyze system dynamics. We make a connection between pulse-gated propagation in
the Fokker-Planck and population-averaged mean-field (firing rate) models, and
then identify an approximate line attractor in state space as the essential
structure underlying graded information propagation. An analysis of the line
attractor shows that it consists of three fixed points: a central saddle with an
unstable manifold along the line and stable manifolds orthogonal to the line,
which is surrounded on either side by stable fixed points. Along the manifold
defined by the fixed points, slow dynamics give rise to a ghost. We show that
this line attractor arises at a cusp catastrophe, where a fold bifurcation
develops as a function of synaptic noise; and that the ghost dynamics near the
fold of the cusp underly the robustness of the line attractor. Understanding the
dynamical aspects of this cusp catastrophe allows us to show how line attractors
can persist in biologically realistic neuronal networks and how the interplay of
pulse gating, synaptic coupling, and neuronal stochasticity can be used to enable
attracting one-dimensional manifolds and, thus, dynamically control the
processing of graded information.
PMID- 29347716
TI - Inferring low-dimensional microstructure representations using convolutional
neural networks.
AB - We apply recent advances in machine learning and computer vision to a central
problem in materials informatics: the statistical representation of
microstructural images. We use activations in a pretrained convolutional neural
network to provide a high-dimensional characterization of a set of synthetic
microstructural images. Next, we use manifold learning to obtain a low
dimensional embedding of this statistical characterization. We show that the low
dimensional embedding extracts the parameters used to generate the images.
According to a variety of metrics, the convolutional neural network method yields
dramatically better embeddings than the analogous method derived from two-point
correlations alone.
PMID- 29347717
TI - Crossover between liquidlike and gaslike behavior in CH_{4} at 400 K.
AB - We report experimental evidence for a crossover between a liquidlike state and a
gaslike state in fluid methane (CH_{4}). This crossover is observed in all of our
experiments, up to a temperature of 397 K, 2.1 times the critical temperature of
methane. The crossover has been characterized with both Raman spectroscopy and x
ray diffraction in a number of separate experiments, and confirmed to be
reversible. We associate this crossover with the Frenkel line-a recently
hypothesized crossover in dynamic properties of fluids extending to arbitrarily
high pressure and temperature, dividing the phase diagram into separate regions
where the fluid possesses liquidlike and gaslike properties. On the liquidlike
side the Raman-active vibration increases in frequency linearly as pressure is
increased, as expected due to the repulsive interaction between adjacent
molecules. On the gaslike side this competes with the attractive van der Waals
potential leading the vibration frequency to decrease as pressure is increased.
PMID- 29347718
TI - Three-body interactions improve contact prediction within direct-coupling
analysis.
AB - The prediction of residue contacts in a protein solely from sequence information
is a promising approach to computational structure prediction. Recent
developments use statistical or information theoretic methods to extract contact
information from a multiple sequence alignment. Despite good results, accuracy is
limited due to usage of two-body interactions within a Potts model. In this paper
we generalize this approach and propose a Hamiltonian with an additional three
body interaction term. We derive a mean-field approximation for inference of
three-body couplings within a Potts model which is fast enough on modern
computers. Finally, we show that our model has a higher accuracy in predicting
residue contacts in comparison with the plain two-body-interaction model.
PMID- 29347719
TI - Effect of polymer network on thermodynamic stability and switching behavior of
the smectic-C_{alpha}^{*} phase.
AB - A polymer-stabilized liquid crystal based on 4^{'}-(octyloxy)biphenyl-4
carboxylate 2-fluoro-4-((octyl-2-yloxy)carbonyl)phenyl (D16) and 1,6 hexanediol
diacrylate as a monomer was prepared by in situ photopolymerization. The selected
antiferroelectric liquid crystal contains a fast-switching smectic C_{alpha}^{*}
phase (SmC_{alpha}^{*}), and the influence of the polymer network on the
thermodynamic stability of this phase and its switching behavior under applying
time-dependent electric field were studied. Using dielectric spectroscopy and
polarizing microscopy, the liquid crystal materials were characterized, and
subsequently with the use of the reversal current method (RCM) the current
response, especially from the SmC_{alpha}^{*} phase was carefully analyzed. The
current response is complex and also depends on the neighboring liquid crystal
phases. In the liquid crystal-polymer system, as well as in the liquid crystal
monomer mixture, a significant shift of the temperature range of the
SmC_{alpha}^{*} phase toward lower temperatures was observed; however, the
thermodynamic instability related to the transformation to the crystalline phase
was also noted and characterized. Because of the fuzzy phase transitions detected
in the liquid crystal-polymer system by dielectric spectroscopy and also because
of the lack of the characteristic dielectric signature of SmC_{alpha}^{*} after
polymerization, we proposed the use of the RCM, as a complementary one, to
identify the SmC_{alpha}^{*} phase even in such complex materials.
PMID- 29347720
TI - Extreme events in the forced Lienard system.
AB - We observe extremely large amplitude intermittent spikings in a dynamical
variable of a periodically forced Lienard-type oscillator and characterize them
as extreme events, which are rare, but recurrent and larger in amplitude than a
threshold. The extreme events occur via two processes, an interior crisis and
intermittency. The probability of occurrence of the events shows a long-tail
distribution in both the cases. We provide evidence of the extreme events in an
experiment using an electronic analog circuit of the Lienard oscillator that
shows good agreement with our numerical results.
PMID- 29347721
TI - Direct verification of the fluctuation-dissipation relation in viscously coupled
oscillators.
AB - The fluctuation-dissipation relation, a central result in nonequilibrium
statistical physics, relates equilibrium fluctuations in a system to its linear
response to external forces. Here we provide a direct experimental verification
of this relation for viscously coupled oscillators, as realized by a pair of
optically trapped colloidal particles. A theoretical analysis, in which
interactions mediated by slow viscous flow are represented by nonlocal friction
tensors, matches experimental results and reveals a frequency maximum in the
amplitude of the mutual response which is a sensitive function of the trap
stiffnesses and the friction tensors. This allows for its location and width to
be tuned and suggests the utility of the trap setup for accurate two-point
microrheology.
PMID- 29347722
TI - Stochastic thermodynamics of periodically driven systems: Fluctuation theorem for
currents and unification of two classes.
AB - Periodic driving is used to operate machines that go from standard macroscopic
engines to small nonequilibrium microsized systems. Two classes of such systems
are small heat engines driven by periodic temperature variations, and molecular
pumps driven by external stimuli. Well-known results that are valid for
nonequilibrium steady states of systems driven by fixed thermodynamic forces,
instead of an external periodic driving, have been generalized to periodically
driven heat engines only recently. These results include a general expression for
entropy production in terms of currents and affinities, and symmetry relations
for the Onsager coefficients from linear-response theory. For nonequilibrium
steady states, the Onsager reciprocity relations can be obtained from the more
general fluctuation theorem for the currents. We prove a fluctuation theorem for
the currents for periodically driven systems. We show that this fluctuation
theorem implies a fluctuation dissipation relation, symmetry relations for
Onsager coefficients, and further relations for nonlinear response coefficients.
The setup in this paper is more general than previous studies, i.e., our results
are valid for both heat engines and molecular pumps. The external protocol is
assumed to be stochastic in our framework, which leads to a particularly
convenient way to treat periodically driven systems.
PMID- 29347723
TI - Hierarchical benchmark graphs for testing community detection algorithms.
AB - Hierarchical organization is an important, prevalent characteristic of complex
systems; to understand their organization, the study of the underlying (generally
complex) networks that describe the interactions between their constituents plays
a central role. Numerous previous works have shown that many real-world networks
in social, biologic, and technical systems present hierarchical organization,
often in the form of a hierarchy of community structures. Many artificial
benchmark graphs have been proposed to test different community detection
methods, but no benchmark has been developed to thoroughly test the detection of
hierarchical community structures. In this study, we fill this vacancy by
extending the Lancichinetti-Fortunato-Radicchi (LFR) ensemble of benchmark
graphs, adopting the rule of constructing hierarchical networks proposed by
Ravasz and Barabasi. We employ this benchmark to test three of the most popular
community detection algorithms and quantify their accuracy using the traditional
mutual information and the recently introduced hierarchical mutual information.
The results indicate that the Ravasz-Barabasi-Lancichinetti-Fortunato-Radicchi
(RB-LFR) benchmark generates a complex hierarchical structure constituting a
challenging benchmark for the considered community detection methods.
PMID- 29347724
TI - Dielectric properties of liquid crystalline dimer mixtures exhibiting the nematic
and twist-bend nematic phases.
AB - A detailed investigation of the thermal and dielectric properties of a series of
binary mixtures exhibiting the nematic (N) and twist-bend nematic (N_{TB}) liquid
crystal phases is presented. The mixtures consist of an achiral, dimeric liquid
crystal CB7CB, which forms the nematic and twist-bend nematic phases, and a
calamitic liquid crystal 5CB, which shows the nematic phase. As the concentration
of the calamitic liquid crystal is increased, the transition temperatures
decrease linearly, and the width of the nematic phase increases. The enthalpies
of phase transitions obtained from DSC measurements show that on increasing the
concentration of 5CB in the binary mixtures, the enthalpy associated with the N
N_{TB} phase transitions reduces considerably compared to a clear first-order N
N_{TB} transition in pure CB7CB. The real and imaginary parts of the dielectric
permittivity are measured as a function of frequency from 100 Hz to 2 MHz in the
nematic and twist-bend nematic phases in planar and homeotropic devices. A
significant decrease in the average dielectric permittivity as a function of
temperature for mixtures forming the N_{TB} phase is observed. Measurements of
the imaginary part of the dielectric permittivity show a relaxation peak in the
measured frequency window for all of the mixtures exhibiting the N_{TB} phase.
The activation energy associated with this relaxation process is calculated and
is shown to remain constant irrespective of the composition of the mixtures.
PMID- 29347725
TI - Partition function zeros of the p-state clock model in the complex temperature
plane.
AB - We investigate the partition function zeros of the two-dimensional p-state clock
model in the complex temperature plane by using the Wang-Landau method. For p=5,
6, 8, and 10, we propose a modified energy representation to enumerate exact
irregular energy levels for the density of states without any binning artifacts.
Comparing the leading zeros between different p's, we provide strong evidence
that the upper transition at p=6 is indeed of the Berezinskii-Kosterlitz-Thouless
(BKT) type in contrast to the claim of the previous Fisher zero study [Phys. Rev.
E 80, 042103 (2009)10.1103/PhysRevE.80.042103]. We find that the leading zeros of
p=6 at the upper transition collapse onto the zero trajectories of the larger p's
including the XY limit while the finite-size behavior of p=5 differs from the
converged behavior of p>=6 within the system sizes examined. In addition, we
argue that the nondivergent specific heat in the BKT transition is responsible
for the small partition function magnitude that decreases exponentially with
increasing system size near the leading zero, fundamentally limiting access to
large systems in search for zeros with an estimator under finite statistical
fluctuations.
PMID- 29347726
TI - Deceleration of one-dimensional mixing by discontinuous mappings.
AB - We present a computational study of a simple one-dimensional map with dynamics
composed of stretching, permutations of equally sized cells, and diffusion. We
observe that the combination of the aforementioned dynamics results in eigenmodes
with long-time exponential decay rates. The decay rate of the eigenmodes is shown
to be dependent on the choice of permutation and changes nonmonotonically with
the diffusion coefficient for many of the permutations. The global mixing rate of
the map M in the limit of vanishing diffusivity approximates well the decay rates
of the eigenmodes for small diffusivity, however this global mixing rate does not
bound the rates for all values of the diffusion coefficient. This
counterintuitively predicts a deceleration in the asymptotic mixing rate with an
increasing diffusivity rate. The implications of the results on finite time
mixing are discussed.
PMID- 29347727
TI - Nonlinear dynamics of a buoyancy-induced turbulent fire.
AB - We conduct a numerical study on the dynamic behavior of a buoyancy-induced
turbulent fire from the viewpoints of symbolic dynamics, complex networks, and
statistical complexity. Here, we consider two classes of entropies: the
permutation entropy and network entropy in epsilon-recurrence networks, both of
which evaluate the degree of randomness in the underlying dynamics. These
entropies enable us to capture the significant changes in the dynamic behavior of
flow velocity fluctuations. The possible presence of two important dynamics, low
dimensional deterministic chaos in the near field dominated by the motion of
large-scale vortices and high-dimensional chaos in the far field forming a well
developed turbulent plume, is clearly identified by the multiscale complexity
entropy causality plane.
PMID- 29347728
TI - Extracting the equation of state of lattice gases from random sequential
adsorption simulations by means of the Gibbs adsorption isotherm.
AB - An alternative approach for deriving the equation of state for a two-dimensional
lattice gas is proposed, based on arguments similar to those used in the
derivation of the Langmuir-Szyszkowski equation of state for localized
adsorption. The relationship between surface coverage and excluded area is first
extracted from random sequential adsorption simulations incorporating surface
diffusion (RSAD). The adsorption isotherm is then obtained using kinetic
arguments, and the Gibbs equation gives the relation between surface pressure and
coverage. Provided surface diffusion is fast enough to ensure internal
equilibrium within the monolayer during the RSAD simulations, the resulting
equations of state are very close to the most accurate equivalents obtained by
cumbersome thermodynamic methods. An internal test of the accuracy of the method
is obtained by noting that adsorption RSAD simulations starting from an empty
lattice and desorption simulations starting from a full lattice provide
convergent upper and lower bounds on the surface pressure.
PMID- 29347729
TI - Single-cone finite-difference schemes for the (2+1)-dimensional Dirac equation in
general electromagnetic textures.
AB - A single-cone finite-difference lattice scheme is developed for the (2+1)
dimensional Dirac equation in presence of general electromagnetic textures. The
latter is represented on a (2+1)-dimensional staggered grid using a second-order
accurate finite difference scheme. A Peierls-Schwinger substitution to the wave
function is used to introduce the electromagnetic (vector) potential into the
Dirac equation. Thereby, the single-cone energy dispersion and gauge invariance
are carried over from the continuum to the lattice formulation. Conservation laws
and stability properties of the formal scheme are identified by comparison with
the scheme for zero vector potential. The placement of magnetization terms is
inferred from consistency with the one for the vector potential. Based on this
formal scheme, several numerical schemes are proposed and tested. Elementary
examples for single-fermion transport in the presence of in-plane magnetization
are given, using material parameters typical for topological insulator surfaces.
PMID- 29347730
TI - Rigidity-induced scale invariance in polymer ejection from capsid.
AB - While the dynamics of a fully flexible polymer ejecting a capsid through a
nanopore has been extensively studied, the ejection dynamics of semiflexible
polymers has not been properly characterized. Here we report results from
simulations of ejection dynamics of semiflexible polymers ejecting from spherical
capsids. Ejections start from strongly confined polymer conformations of constant
initial monomer density. We find that, unlike for fully flexible polymers, for
semiflexible polymers the force measured at the pore does not show a direct
relation to the instantaneous ejection velocity. The cumulative waiting time
t(s), that is, the time at which a monomer s exits the capsid the last time,
shows a clear change when increasing the polymer rigidity kappa. The major part
of an ejecting polymer is driven out of the capsid by internal pressure. At the
final stage the polymer escapes the capsid by diffusion. For the driven part
there is a crossover from essentially exponential growth of t with s of the fully
flexible polymers to a scale-invariant form. In addition, a clear dependence of t
on polymer length N_{0} was found. These findings combined give the dependence
t(s)?N_{0}^{0.55}s^{1.33} for the strongly rigid polymers. This crossover in
dynamics where kappa acts as a control parameter is reminiscent of a phase
transition. This analogy is further enhanced by our finding a perfect data
collapse of t for polymers of different N_{0} and any constant kappa.
PMID- 29347731
TI - Delay-induced wave instabilities in single-species reaction-diffusion systems.
AB - The Turing (wave) instability is only possible in reaction-diffusion systems with
more than one (two) components. Motivated by the fact that a time delay increases
the dimension of a system, we investigate the presence of diffusion-driven
instabilities in single-species reaction-diffusion systems with delay. The
stability of arbitrary one-component systems with a single discrete delay, with
distributed delay, or with a variable delay is systematically analyzed. We show
that a wave instability can appear from an equilibrium of single-species reaction
diffusion systems with fluctuating or distributed delay, which is not possible in
similar systems with constant discrete delay or without delay. More precisely, we
show by basic analytic arguments and by numerical simulations that fast
asymmetric delay fluctuations or asymmetrically distributed delays can lead to
wave instabilities in these systems. Examples, for the resulting traveling waves
are shown for a Fisher-KPP equation with distributed delay in the reaction term.
In addition, we have studied diffusion-induced instabilities from homogeneous
periodic orbits in the same systems with variable delay, where the homogeneous
periodic orbits are attracting resonant periodic solutions of the system without
diffusion, i.e., periodic orbits of the Hutchinson equation with time-varying
delay. If diffusion is introduced, standing waves can emerge whose temporal
period is equal to the period of the variable delay.
PMID- 29347732
TI - Population equations for degree-heterogenous neural networks.
AB - We develop a statistical framework for studying recurrent networks with broad
distributions of the number of synaptic links per neuron. We treat each group of
neurons with equal input degree as one population and derive a system of
equations determining the population-averaged firing rates. The derivation rests
on an assumption of a large number of neurons and, additionally, an assumption of
a large number of synapses per neuron. For the case of binary neurons, analytical
solutions can be constructed, which correspond to steps in the activity versus
degree space. We apply this theory to networks with degree-correlated topology
and show that complex, multi-stable regimes can result for increasing
correlations. Our work is motivated by the recent finding of subnetworks of
highly active neurons and the fact that these neurons tend to be connected to
each other with higher probability.
PMID- 29347733
TI - Lattice Boltzmann model capable of mesoscopic vorticity computation.
AB - It is well known that standard lattice Boltzmann (LB) models allow the strain
rate components to be computed mesoscopically (i.e., through the local particle
distributions) and as such possess a second-order accuracy in strain rate. This
is one of the appealing features of the lattice Boltzmann method (LBM) which is
of only second-order accuracy in hydrodynamic velocity itself. However, no known
LB model can provide the same quality for vorticity and pressure gradients. In
this paper, we design a multiple-relaxation time LB model on a three-dimensional
27-discrete-velocity (D3Q27) lattice. A detailed Chapman-Enskog analysis is
presented to illustrate all the necessary constraints in reproducing the
isothermal Navier-Stokes equations. The remaining degrees of freedom are
carefully analyzed to derive a model that accommodates mesoscopic computation of
all the velocity and pressure gradients from the nonequilibrium moments. This way
of vorticity calculation naturally ensures a second-order accuracy, which is also
proven through an asymptotic analysis. We thus show, with enough degrees of
freedom and appropriate modifications, the mesoscopic vorticity computation can
be achieved in LBM. The resulting model is then validated in simulations of a
three-dimensional decaying Taylor-Green flow, a lid-driven cavity flow, and a
uniform flow passing a fixed sphere. Furthermore, it is shown that the mesoscopic
vorticity computation can be realized even with single relaxation parameter.
PMID- 29347734
TI - Electrically induced structure transition in nematic liquid crystal droplets with
conical boundary conditions.
AB - Polymer-dispersed liquid crystal composites have been a focus of study for a long
time for their unique electro-optical properties and manufacturing by "bottom-up"
techniques at large scales. In this paper, nematic liquid crystal oblate droplets
with conical boundary conditions (CBCs) under the action of electric field were
studied by computer simulations and polarized optical microscopy. Droplets with
CBCs were shown to prefer an axial-bipolar structure, which combines a pair of
boojums and circular disclinations on a surface. In contrast to droplets with
degenerate planar boundary conditions (PBCs), hybridization of the two structure
types in droplets with CBCs leads to a two-minima energy profile, resulting in an
abrupt structure transition and bistable behavior of the system. The nature of
the low-energy barrier in droplets with CBCs makes it highly sensitive to
external stimuli, such as electric or magnetic fields, temperature, and light. In
particular, the value of the electric field of the structure reorientation in
droplets with CBCs was found to be a few times smaller than the one for droplets
with PBCs, and the droplet state remained stable after switching off the voltage.
PMID- 29347735
TI - Spreading of nonmotile bacteria on a hard agar plate: Comparison between agent
based and stochastic simulations.
AB - We study spreading of a nonmotile bacteria colony on a hard agar plate by using
agent-based and continuum models. We show that the spreading dynamics depends on
the initial nutrient concentration, the motility, and the inherent demographic
noise. Population fluctuations are inherent in an agent-based model, whereas for
the continuum model we model them by using a stochastic Langevin equation. We
show that the intrinsic population fluctuations coupled with nonlinear
diffusivity lead to a transition from a diffusion limited aggregation type of
morphology to an Eden-like morphology on decreasing the initial nutrient
concentration.
PMID- 29347736
TI - Locality of interactions for planar memristive circuits.
AB - The dynamics of purely memristive circuits has been shown to depend on a
projection operator which expresses the Kirchhoff constraints, is naturally non
local in nature, and does represent the interaction between memristors. In the
present paper we show that for the case of planar circuits, for which a
meaningful Hamming distance can be defined, the elements of such projector can be
bounded by exponentially decreasing functions of the distance. We provide a
geometrical interpretation of the projector elements in terms of determinants of
Dirichlet Laplacian of the dual circuit. For the case of linearized dynamics of
the circuit for which a solution is known, this can be shown to provide a light
cone bound for the interaction between memristors. This result establishes a
finite speed of propagation of signals across the network, despite the non-local
nature of the system.
PMID- 29347737
TI - Influence of topographically patterned angled guidelines on directed self
assembly of block copolymers.
AB - Single chain in mean-field Monte Carlo simulations were employed to study the
self-assembly of block copolymers (BCP) in thin films that use trapezoidal
guidelines to direct the orientation and alignment of lamellar patterns. The
present study explored the influence of sidewall interactions and geometry of the
trapezoidal guidelines on the self-assembly of perpendicularly oriented lamellar
morphologies. When both the sidewall and the top surface exhibit preferential
interactions to the same block of the BCP, trapezoidal guidelines with
intermediate taper angles were found to result in less defective perpendicularly
orientated morphologies. Similarly, when the sidewall and top surface are
preferential to distinct blocks of the BCP, intermediate tapering angles were
found to be optimal in promoting defect free structures. Such results are
rationalized based on the energetics arising in the formation of perpendicularly
oriented lamella on patterned substrates.
PMID- 29347738
TI - Finite-range Coulomb gas models of banded random matrices and quantum kicked
rotors.
AB - Dyson demonstrated an equivalence between infinite-range Coulomb gas models and
classical random matrix ensembles for the study of eigenvalue statistics. We
introduce finite-range Coulomb gas (FRCG) models via a Brownian matrix process,
and study them analytically and by Monte Carlo simulations. These models yield
new universality classes, and provide a theoretical framework for the study of
banded random matrices (BRMs) and quantum kicked rotors (QKRs). We demonstrate
that, for a BRM of bandwidth b and a QKR of chaos parameter alpha, the
appropriate FRCG model has the effective range d=b^{2}/N=alpha^{2}/N, for large N
matrix dimensionality. As d increases, there is a transition from Poisson to
classical random matrix statistics.
PMID- 29347739
TI - Fluid-driven fracture propagation in heterogeneous media: Probability
distributions of fracture trajectories.
AB - Hydraulic fracture trajectories in rocks and other materials are highly affected
by spatial heterogeneity in their mechanical properties. Understanding the
complexity and structure of fluid-driven fractures and their deviation from the
predictions of homogenized theories is a practical problem in engineering and
geoscience. We conduct a Monte Carlo simulation study to characterize the
influence of heterogeneous mechanical properties on the trajectories of hydraulic
fractures propagating in elastic media. We generate a large number of random
fields of mechanical properties and simulate pressure-driven fracture propagation
using a phase-field model. We model the mechanical response of the material as
that of an elastic isotropic material with heterogeneous Young modulus and
Griffith energy release rate, assuming that fractures propagate in the toughness
dominated regime. Our study shows that the variance and the spatial covariance of
the mechanical properties are controlling factors in the tortuousness of the
fracture paths. We characterize the deviation of fracture paths from the
homogenous case statistically, and conclude that the maximum deviation grows
linearly with the distance from the injection point. Additionally, fracture path
deviations seem to be normally distributed, suggesting that fracture propagation
in the toughness-dominated regime may be described as a random walk.
PMID- 29347740
TI - Evolving power grids with self-organized intermittent strain releases: An analogy
with sandpile models and earthquakes.
AB - The stability of powergrid is crucial since its disruption affects systems
ranging from street lightings to hospital life-support systems. While short-term
dynamics of single-event cascading failures have been extensively studied, less
is understood on the long-term evolution and self-organization of powergrids. In
this paper, we introduce a simple model of evolving powergrid and establish its
connection with the sandpile model and earthquakes, i.e., self-organized systems
with intermittent strain releases. Various aspects during its self-organization
are examined, including blackout magnitudes, their interevent waiting time, the
predictability of large blackouts, as well as the spatiotemporal rescaling of
blackout data. We examined the self-organized strain releases on simulated
networks as well as the IEEE 118-bus system, and we show that both simulated and
empirical blackout waiting times can be rescaled in space and time similarly to
those observed between earthquakes. Finally, we suggested proactive maintenance
strategies to drive the powergrids away from self-organization to suppress large
blackouts.
PMID- 29347741
TI - Perturbation theory for water with an associating reference fluid.
AB - The theoretical description of the thermodynamics of water is challenged by the
structural transition towards tetrahedral symmetry at ambient conditions. As
perturbation theories typically assume a spherically symmetric reference fluid,
they are incapable of accurately describing the liquid properties of water at
ambient conditions. In this paper we address this problem by introducing the
concept of an associated reference perturbation theory (APT). In APT we treat the
reference fluid as an associating hard sphere fluid which transitions to
tetrahedral symmetry in the fully hydrogen bonded limit. We calculate this
transition in a theoretically self-consistent manner without appealing to
molecular simulations. This associated reference provides the reference fluid for
a second order Barker-Henderson perturbative treatment of the long-range
attractions. We demonstrate that this approach gives a significantly improved
description of water as compared to standard perturbation theories.
PMID- 29347742
TI - Exact solution of the hidden Markov processes.
AB - We write a master equation for the distributions related to hidden Markov
processes (HMPs) and solve it using a functional equation. Thus the solution of
HMPs is mapped exactly to the solution of the functional equation. For a general
case the latter can be solved only numerically. We derive an exact expression for
the entropy of HMPs. Our expression for the entropy is an alternative to the ones
given before by the solution of integral equations. The exact solution is
possible because actually the model can be considered as a generalized random
walk on a one-dimensional strip. While we give the solution for the two second
order matrices, our solution can be easily generalized for the L values of the
Markov process and M values of observables: We should be able to solve a system
of L functional equations in the space of dimension M-1.
PMID- 29347743
TI - Flat bands and compactons in mechanical lattices.
AB - Local configurational symmetry in lattice structures may give rise to stationary,
compact solutions, even in the absence of disorder and nonlinearity. These
compact solutions are related to the existence of flat dispersion curves (bands).
Nonlinearity can destabilize such compactons. One common flat-band-generating
system is the one-dimensional cross-stitch model, in which compactons were shown
to exist for the photonic lattice with Kerr nonlinearity. The compactons exist
there already in the linear regime and are not generally destructed by that
nonlinearity. Smooth nonlinearity of this kind does not permit performing
complete stability analysis for this chain. We consider a discrete mechanical
system with flat dispersion bands, in which the nonlinearity exists due to impact
constraints. In this case, one can use the concept of the saltation matrix for
the analytic construction of the monodromy matrix. Besides, we consider a smooth
nonlinear lattice with linearly connected massless boxes, each containing two
symmetric anharmonic oscillators. In this model, the flat bands and discrete
compactons also readily emerge. This system also permits performing comprehensive
stability analysis, at least in the anticontinuum limit, due to the reduced
number of degrees of freedom. In both systems, there exist two types of
localization. The first one is the complete localization, and the second one is
the more common exponential localization. The latter type is associated with
discrete breathers (DBs). Two principal mechanisms for the loss of stability are
revealed. The first one is the possible internal instability of the symmetric
and/or antisymmetric solution in the individual unit cell of the chain. One can
interpret this instability pattern as internal resonance between the compacton
and the DB. The other mechanism is global instability related to resonance of the
stationary solution with the propagation frequencies. Different instability
mechanisms lead to different bifurcations at the stability threshold.
PMID- 29347744
TI - Quantum fluctuations of entropy production for fermionic systems in the Landauer
Buttiker state.
AB - The quantum fluctuations of the entropy production for fermionic systems in the
Landauer-Buttiker nonequilibrium steady state are investigated. The probability
distribution, governing these fluctuations, is explicitly derived by means of
quantum field theory methods and analyzed in the zero frequency limit. It turns
out that microscopic processes with positive, vanishing and negative entropy
production occur in the system with nonvanishing probability. In spite of this
fact, we show that all odd moments (in particular, the mean value of the entropy
production) of the above distribution are non-negative. This result extends the
second principle of thermodynamics to the quantum fluctuations of the entropy
production in the Landauer-Buttiker state. The effect of the time reversal is
also discussed.
PMID- 29347746
TI - Topological defects in two-dimensional orientation-field models for grain growth.
AB - Standard two-dimensional orientation-field-based phase-field models rely on a
continuous scalar field to represent crystallographic orientation. The
corresponding order parameter space is the unit circle, which is not simply
connected. This topological property has important consequences for the resulting
multigrain structures: (i) trijunctions may be singular; (ii) for each pair of
grains there exist two different grain boundary solutions that cannot
continuously transform to one another; (iii) if both solutions appear along a
grain boundary, a topologically stable, singular point defect must exist between
them. While (i) can be interpreted in the classical picture of grain boundaries,
(ii) and therefore (iii) cannot. In addition, singularities cause difficulties,
such as lattice pinning in numerical simulations. To overcome these problems, we
propose two formulations of the model. The first is based on a three-component
unit vector field, while in the second we utilize a two-component vector field
with an additional potential. In both cases, the additional degree of freedom
introduced makes the order parameter space simply connected, which removes the
topological stability of these defects.
PMID- 29347745
TI - Multiplexing topologies and time scales: The gains and losses of synchrony.
AB - Inspired by the recent interest in collective dynamics of biological neural
networks immersed in the glial cell medium, we investigate the frequency and
phase order, i.e., Kuramoto type of synchronization in a multiplex two-layer
network of phase oscillators of different time scales and topologies. One of them
has a long-range connectivity, exemplified by the Erdos-Renyi random network, and
supports both kinds of synchrony. The other is a locally coupled two-dimensional
lattice that can reach frequency synchronization but lacks phase order.
Drastically different layer frequencies disentangle intra- and interlayer
synchronization. We find that an indirect but sufficiently strong coupling
through the regular layer can induce both phase order in the originally
nonsynchronized random layer and global order, even when an isolated regular
layer does not manifest it in principle. At the same time, the route to global
synchronization is complex: an initial onset of (partial) synchrony in the
regular layer, when its intra- and interlayer coupling is increased, provokes the
loss of synchrony even in the originally synchronized random layer. Ultimately, a
developed asynchronous dynamics in both layers is abruptly taken over by the
global synchrony of both kinds.
PMID- 29347747
TI - Dynamical transition on the periodic Lorentz gas: Stochastic and deterministic
approaches.
AB - The effect of dynamical properties of the periodic Lorentz gas on the
autocorrelation function and diffusion coefficient are investigated in various
geometric transitions between billiards without horizon and infinite horizon.
Numerical simulations are performed using a double square lattice which permits
us to isolate different types of corridors and to describe the individual effects
of each corridor. The results are compared with a stochastic model based on a
escape-rate formalism which reveals the sensibility of the diffusion coefficient
and clarifies the role of the open corridors mechanism on the dynamical
transitions.
PMID- 29347748
TI - Asymmetric couplings enhance the transition from chimera state to
synchronization.
AB - Chimera state has been well studied recently, but little attention has been paid
to its transition to synchronization. We study this topic here by considering two
groups of adaptively coupled Kuramoto oscillators. By searching the final states
of different initial conditions, we find that the system can easily show a
chimera state with robustness to initial conditions, in contrast to the sensitive
dependence of chimera state on initial conditions in previous studies. Further,
we show that, in the case of symmetric couplings, the behaviors of the two groups
are always complementary to each other, i.e., robustness of chimera state, except
a small basin of synchronization. Interestingly, we reveal that the basin of
synchronization will be significantly increased when either the coupling of inner
groups or that of intergroups are asymmetric. This transition from the attractor
of chimera state to the attractor of synchronization is closely related to both
the phase delay and the asymmetric degree of coupling strengths, resulting in a
diversity of attractor's patterns. A theory based on the Ott-Antonsen ansatz is
given to explain the numerical simulations. This finding may be meaningful for
the control of competition between two attractors in biological systems, such as
the cardiac rhythm and ventricular fibrillation, etc.
PMID- 29347749
TI - Confined sandpile in two dimensions: Percolation and singular diffusion.
AB - We investigate the properties of a two-state sandpile model subjected to a
confining potential in two dimensions. From the microdynamical description, we
derive a diffusion equation, and find a stationary solution for the case of a
parabolic confining potential. By studying the systems at different confining
conditions, we observe two scale-invariant regimes. At a given confining
potential strength, the cluster size distribution takes the form of a power law.
This regime corresponds to the situation in which the density at the center of
the system approaches the critical percolation threshold. The analysis of the
fractal dimension of the largest cluster frontier provides evidence that this
regime is reminiscent of gradient percolation. By increasing further the
confining potential, most of the particles coalesce in a giant cluster, and we
observe a regime where the jump size distribution takes the form of a power law.
The onset of this second regime is signaled by a maximum in the fluctuation of
energy.
PMID- 29347750
TI - Benchmarking of three-dimensional multicomponent lattice Boltzmann equation.
AB - We present a challenging validation of phase field multicomponent lattice
Boltzmann equation (MCLBE) simulation against the Re=0 Stokes flow regime Taylor
Einstein theory of dilute suspension viscosity. By applying a number of recent
advances in the understanding and the elimination of the interfacial microcurrent
artefact, extending to a three-dimensional class of stability-enhancing multiple
relaxation time collision models (which require no explicit collision matrix,
note) and developing new interfacial interpolation schemes, we are able to obtain
data that show that MCLBE may be applied in new flow regimes. Our data represent
one of the most stringent tests yet attempted on LBE-one which received wisdom
would preclude on grounds of overwhelming artefact flow.
PMID- 29347751
TI - Surface deformation during an action potential in pearled cells.
AB - Electric pulses in biological cells (action potentials) have been reported to be
accompanied by a propagating cell-surface deformation with a nanoscale amplitude.
Typically, this cell surface is covered by external layers of polymer material
(extracellular matrix, cell wall material, etc.). It was recently demonstrated in
excitable plant cells (Chara braunii) that the rigid external layer (cell wall)
hinders the underlying deformation. When the cell membrane was separated from the
cell wall by osmosis, a mechanical deformation, in the micrometer range, was
observed upon excitation of the cell. The underlying mechanism of this mechanical
pulse has, to date, remained elusive. Herein we report that Chara cells can
undergo a pearling instability, and when the pearled fragments were excited even
larger and more regular cell shape changes were observed (~10-100MUm in
amplitude). These transient cellular deformations were captured by a curvature
model that is based on three parameters: surface tension, bending rigidity, and
pressure difference across the surface. In this paper these parameters are
extracted by curve-fitting to the experimental cellular shapes at rest and during
excitation. This is a necessary step to identify the mechanical parameters that
change during an action potential.
PMID- 29347752
TI - Noise-driven current reversal and stabilization in the tilted ratchet potential
subject to tempered stable Levy noise.
AB - We consider motion of a particle in a one-dimensional tilted ratchet potential
subject to two-sided tempered stable Levy noise characterized by strength Omega,
fractional index alpha, skew theta, and tempering lambda. We derive analytic
solutions to the corresponding Fokker-Planck Levy equations for the probability
density. Due to the periodicity of the potential, we carry out reduction to a
compact domain and solve for the analog of steady-state solutions which we
represent as wrapped probability density functions. By solving for the expected
value of the current associated with the particle motion, we are able to
determine thresholds for metastability of the system, namely when the particle
stabilizes in a well of the potential and when the particle is in motion, for
example as a consequence of the tilt of the potential. Because the noise may be
asymmetric, we examine the relationship between skew of the noise and the tilt of
the potential. With tempering, we find two remarkable regimes where the current
may be reversed in a direction opposite to the tilt or where the particle may be
stabilized in a well in circumstances where deterministically it should flow with
the tilt.
PMID- 29347753
TI - Consistent forcing scheme in the cascaded lattice Boltzmann method.
AB - In this paper, we give an alternative derivation for the cascaded lattice
Boltzmann method (CLBM) within a general multiple-relaxation-time (MRT) framework
by introducing a shift matrix. When the shift matrix is a unit matrix, the CLBM
degrades into an MRT LBM. Based on this, a consistent forcing scheme is developed
for the CLBM. The consistency of the nonslip rule, the second-order convergence
rate in space, and the property of isotropy for the consistent forcing scheme is
demonstrated through numerical simulations of several canonical problems. Several
existing forcing schemes previously used in the CLBM are also examined. The study
clarifies the relation between MRT LBM and CLBM under a general framework.
PMID- 29347754
TI - Theory of corticothalamic brain activity in a spherical geometry: Spectra,
coherence, and correlation.
AB - Corticothalamic neural field theory is applied to a spherical geometry to better
model neural activity in the human brain and is also compared with planar
approximations. The frequency power spectrum, correlation, and coherence
functions are computed analytically and numerically. The effects of cortical
boundary conditions and resulting modal aspects of spherical corticothalamic
dynamics are explored, showing that the results of spherical and finite planar
geometries converge to those for the infinite planar geometry in the limit of
large brain size. Estimates are made of the point at which modal series can be
truncated and it is found that for physiologically plausible parameters only the
lowest few spatial eigenmodes are needed for an accurate representation of
macroscopic brain activity. A difference between the geometries is that there is
a low-frequency 1/f spectrum in the infinite planar geometry, whereas in the
spherical geometry it is 1/f^{2}. Another difference is that the alpha peak in
the spherical geometry is sharper and stronger than in the planar geometry.
Cortical modal effects can lead to a double alpha peak structure in the power
spectrum, although the main determinant of the alpha peak is corticothalamic
feedback. In the spherical geometry, the cross spectrum between two points is
found to only depend on their relative distance apart. At small spatial
separations the low-frequency cross spectrum is stronger than for an infinite
planar geometry and the alpha peak is sharper and stronger due to the
partitioning of the energy into discrete modes. In the spherical geometry, the
coherence function between points decays monotonically as their separation
increases at a fixed frequency, but persists further at resonant frequencies. The
correlation between two points is found to be positive, regardless of the time
lag and spatial separation, but decays monotonically as the separation increases
at fixed time lag. At fixed distance the correlation has peaks at multiples of
the period of the dominant frequency of system activity.
PMID- 29347755
TI - Transition to synchrony in degree-frequency correlated Sakaguchi-Kuramoto model.
AB - We investigate transition to synchrony in degree-frequency correlated Sakaguchi
Kuramoto (SK) model on complex networks both analytically and numerically. We
analytically derive self-consistent equations for group angular velocity and
order parameter for the model in the thermodynamic limit. Using the self
consistent equations we investigate transition to synchronization in SK model on
uncorrelated scale-free (SF) and Erdos-Renyi (ER) networks in detail. Depending
on the degree distribution exponent (gamma) of SF networks and phase-frustration
parameter, the population undergoes from first-order transition [explosive
synchronization (ES)] to second-order transition and vice versa. In ER networks
transition is always second order irrespective of the values of the phase-lag
parameter. We observe that the critical coupling strength for the onset of
synchronization is decreased by phase-frustration parameter in case of SF network
where as in ER network, the phase-frustration delays the onset of
synchronization. Extensive numerical simulations using SF and ER networks are
performed to validate the analytical results. An analytical expression of
critical coupling strength for the onset of synchronization is also derived from
the self-consistent equations considering the vanishing order parameter limit.
PMID- 29347756
TI - Improved understanding of the acoustophoretic focusing of dense suspensions in a
microchannel.
AB - We provide improved understanding of acoustophoretic focusing of a dense
suspension (volume fraction phi>10%) in a microchannel subjected to an acoustic
standing wave using a proposed theoretical model and experiments. The model is
based on the theory of interacting continua and utilizes a momentum transport
equation for the mixture, continuity equation, and transport equation for the
solid phase. The model demonstrates the interplay between acoustic radiation and
shear-induced diffusion (SID) forces that is critical in the focusing of dense
suspensions. The shear-induced particle migration model of Leighton and Acrivos,
coupled with the acoustic radiation force, is employed to simulate the continuum
behavior of particles. In the literature, various closures for the diffusion
coefficient D_{phi}^{*} are available for rigid spheres at high concentrations
and nonspherical deformable particles [e.g., red blood cells (RBCs)] at low
concentrations. Here we propose a closure for D_{phi}^{*} for dense suspension of
RBCs and validate the proposed model with experimental data. While the available
closures for D_{phi}^{*} fail to predict the acoustic focusing of a dense
suspension of nonspherical deformable particles like RBCs, the predictions of the
proposed model match experimental data within 15%. Both the model and experiments
reveal a competition between acoustic radiation and SID forces that gives rise to
an equilibrium width w^{*} of a focused stream of particles at some distance
L_{eq}^{*} along the flow direction. Using different shear rates, acoustic energy
densities, and particle concentrations, we show that the equilibrium width is
governed by Peclet number Pe and Strouhal number Stasw^{*}=1.4(PeSt)^{-0.5} while
the length required to obtain the equilibrium-focused width depends on St as
L_{eq}^{*}=3.8/(St)^{0.6}. The proposed model and correlations would find
significance in the design of microchannels for acoustic focusing of dense
suspensions such as undiluted blood.
PMID- 29347757
TI - Evolution of the pore size distribution in sheared binary glasses.
AB - Molecular dynamics simulations are carried out to investigate mechanical
properties and porous structure of binary glasses subjected to steady shear. The
model vitreous systems were prepared via thermal quench at constant volume to a
temperature well below the glass transition. The quiescent samples are
characterized by a relatively narrow pore size distribution whose mean size is
larger at lower glass densities. We find that in the linear regime of
deformation, the shear modulus is a strong function of porosity, and the
individual pores become slightly stretched while their structural topology
remains unaffected. By contrast, with further increasing strain, the shear stress
saturates to a density-dependent plateau value, which is accompanied by pore
coalescence and a gradual development of a broader pore size distribution with a
discrete set of peaks at large length scales.
PMID- 29347758
TI - Turbulent diffusion of chemically reacting flows: Theory and numerical
simulations.
AB - The theory of turbulent diffusion of chemically reacting gaseous admixtures
developed previously [T. Elperin et al., Phys. Rev. E 90, 053001 (2014)PLEEE81539
375510.1103/PhysRevE.90.053001] is generalized for large yet finite Reynolds
numbers and the dependence of turbulent diffusion coefficient on two parameters,
the Reynolds number and Damkohler number (which characterizes a ratio of
turbulent and reaction time scales), is obtained. Three-dimensional direct
numerical simulations (DNSs) of a finite-thickness reaction wave for the first
order chemical reactions propagating in forced, homogeneous, isotropic, and
incompressible turbulence are performed to validate the theoretically predicted
effect of chemical reactions on turbulent diffusion. It is shown that the
obtained DNS results are in good agreement with the developed theory.
PMID- 29347759
TI - Isochoric, isobaric, and ultrafast conductivities of aluminum, lithium, and
carbon in the warm dense matter regime.
AB - We study the conductivities sigma of (i) the equilibrium isochoric state
sigma_{is}, (ii) the equilibrium isobaric state sigma_{ib}, and also the (iii)
nonequilibrium ultrafast matter state sigma_{uf} with the ion temperature T_{i}
less than the electron temperature T_{e}. Aluminum, lithium, and carbon are
considered, being increasingly complex warm dense matter systems, with carbon
having transient covalent bonds. First-principles calculations, i.e., neutral
pseudoatom (NPA) calculations and density-functional theory (DFT) with molecular
dynamics (MD) simulations, are compared where possible with experimental data to
characterize sigma_{ic}, sigma_{ib}, and sigma_{uf}. The NPA sigma_{ib} is
closest to the available experimental data when compared to results from DFT with
MD simulations, where simulations of about 64-125 atoms are typically used. The
published conductivities for Li are reviewed and the value at a temperature of
4.5 eV is examined using supporting x-ray Thomson-scattering calculations. A
physical picture of the variations of sigma with temperature and density
applicable to these materials is given. The insensitivity of sigma to T_{e} below
10 eV for carbon, compared to Al and Li, is clarified.
PMID- 29347760
TI - Anomalies in the equilibrium and nonequilibrium properties of correlated ions in
complex molecular environments.
AB - Emergent statistical attributes, and therefore the equations of state, of an
assembly of interacting charge carriers embedded within a complex molecular
environment frequently exhibit a variety of anomalies, particularly in the high
density (equivalently, the concentration) regime, which are not well understood,
because they do not fall under the low-concentration phenomenologies of Debye
Huckel-Onsager and Poisson-Nernst-Planck, including their variants. To go beyond,
we here use physical concepts and mathematical tools from quantum scattering
theory, transport theory with the Stosszahlansatz of Boltzmann, and classical
electrodynamics (Lorentz gauge) and obtain analytical expressions both for the
average and the frequency-wave vector-dependent longitudinal and transverse
current densities, diffusion coefficient, and the charge density, and therefore
the analytical expressions for (a) the chemical potential, activity coefficient,
and the equivalent conductivity for strong electrolytes and (b) the current
voltage characteristics for ion-transport processes in complex molecular
environments. Using a method analogous to the notion of Debye length and thence
the electrical double layer, we here identify a pair of characteristic length
scales (longitudinal and the transverse), which, being wave vector and frequency
dependent, manifestly exhibit nontrivial fluctuations in space-time. As a
unifying theme, we advance a quantity (inverse length dimension), g_{scat}^{(a)},
which embodies all dynamical interactions, through various quantum scattering
lengths, relevant to molecular species a, and the analytical behavior which helps
us to rationalize the properties of strong electrolytes, including anomalies, in
all concentration regimes. As an example, the behavior of g_{scat}^{(a)} in the
high-concentration regime explains the anomalous increase of the Debye length
with concentration, as seen in a recent experiment on electrolyte solutions. We
also put forth an extension of the standard diffusion equation, which manifestly
incorporates the effects arising from the underlying microscopic collisions among
constituent molecular species. Furthermore, we show a nontrivial connection
between the current-voltage characteristics of electrolyte solutions and the
Landauer's approach to electrical conduction in mesoscopic solids and thereby
establish a definite conceptual bridge between the two disjoint subjects. For
numerical insight, we present results on the aqueous solution of KCl as an
example of strong electrolyte, and the transport (conduction as well as
diffusion) of K^{+} ions in water, as an example of ion transport across the
voltage-gated channels in biological cells.
PMID- 29347761
TI - Analytical mesoscale modeling of aeolian sand transport.
AB - The mesoscale structure of aeolian sand transport determines a variety of natural
phenomena studied in planetary and Earth science. We analyze it theoretically
beyond the mean-field level, based on the grain-scale transport kinetics and
splash statistics. A coarse-grained analytical model is proposed and verified by
numerical simulations resolving individual grain trajectories. The predicted
height-resolved sand flux and other important characteristics of the aeolian
transport layer agree remarkably well with a comprehensive compilation of field
and wind-tunnel data, suggesting that the model robustly captures the essential
mesoscale physics. By comparing the predicted saturation length with field data
for the minimum sand-dune size, we elucidate the importance of intermittent
turbulent wind fluctuations for field measurements and reconcile conflicting
previous models for this most enigmatic emergent aeolian scale.
PMID- 29347762
TI - Modified mean-field theory of the magnetic properties of concentrated, high
susceptibility, polydisperse ferrofluids.
AB - The effects of particle-size polydispersity on the magnetostatic properties of
concentrated ferrofluids are studied using theory and computer simulation. The
second-order modified mean-field (MMF2) theory of Ivanov and Kuznetsova [Phys.
Rev. E 64, 041405 (2001)1063-651X10.1103/PhysRevE.64.041405] has been extended by
calculating additional terms of higher order in the dipolar coupling constant in
the expansions of the initial magnetic susceptibility and the magnetization
curve. The theoretical predictions have been tested rigorously against results
from Monte Carlo simulations of model monodisperse, bidisperse, and highly
polydisperse ferrofluids. Comparisons have been made between systems with the
same Langevin susceptibility and the same saturation magnetization. In all cases,
the new theoretical magnetization curve shows better agreement with simulation
data than does the MMF2 theory. As for the initial susceptibility, MMF2 theory is
most accurate for the monodisperse model, while the new theory works best for
polydisperse systems with a significant proportion of large particles. These
results are important for the analysis and characterization of recently
synthesized polydisperse ferrofluids with record-breaking values of the initial
magnetic susceptibility.
PMID- 29347763
TI - Rayleigh-Taylor instability and vortex rings in coupled Gross-Pitaevskii
equations.
AB - The Rayleigh-Taylor instability is a gravitational instability in two fluids
where the heavier fluid is set over the lighter fluid. The instability occurs
both in classical fluids and quantum fluids. We numerically study the Rayleigh
Taylor instability using coupled Gross-Pitaevskii equations for two-component
Bose-Einstein condensates. We carry out numerical simulations that the heavier
component is set in a torus initially which is surrounded by the lighter
component. When the torus falls, the Rayleigh-Taylor instability develops and a
sagging pattern appears. This instability is investigated for the two cases with
and without a vortex ring inside the torus. We find that a vortex ring suppresses
the instability when the radius of the torus is small.
PMID- 29347764
TI - Exact relations for energy transfer in self-gravitating isothermal turbulence.
AB - Self-gravitating isothermal supersonic turbulence is analyzed in the asymptotic
limit of large Reynolds numbers. Based on the inviscid invariance of total
energy, an exact relation is derived for homogeneous (not necessarily isotropic)
turbulence. A modified definition for the two-point energy correlation functions
is used to comply with the requirement of detailed energy equipartition in the
acoustic limit. In contrast to the previous relations (S. Galtier and S.
Banerjee, Phys. Rev. Lett. 107, 134501 (2011)PRLTAO0031
900710.1103/PhysRevLett.107.134501; S. Banerjee and S. Galtier, Phys. Rev. E 87,
013019 (2013)PLEEE81539-375510.1103/PhysRevE.87.013019), the current exact
relation shows that the pressure dilatation terms play practically no role in the
energy cascade. Both the flux and source terms are written in terms of two-point
differences. Sources enter the relation in a form of mixed second-order structure
functions. Unlike the kinetic and thermodynamic potential energies, the
gravitational contribution is absent from the flux term. An estimate shows that,
for the isotropic case, the correlation between density and gravitational
acceleration may play an important role in modifying the energy transfer in self
gravitating turbulence. The exact relation is also written in an alternative form
in terms of two-point correlation functions, which is then used to describe scale
by-scale energy budget in spectral space.
PMID- 29347765
TI - Laser-excited motion of liquid crystals confined in a microsized volume with a
free surface.
AB - The thermally excited vortical flow in a microsized liquid crystal (LC) volume
with a free LC-air interface has been investigated theoretically based on the
nonlinear extension of the Ericksen-Leslie theory, with accounting the entropy
balance equation. Analysis of the numerical results show that due to interaction
between the gradients of the director field ?n[over ] and temperature field ?T,
caused by the focused heating, the thermally excited vortical fluid flow is
maintained in the vicinity of the heat source. Calculations show that the
magnitude and direction of the velocity field v, as well as the height of the LC
air interface are influenced by the depth of the heat penetration in the LC
volume. It has been shown that there is the point in the vicinity of the LC-air
interface where the thermally excited vortical flow changes the direction from
anticlockwise to clockwise.
PMID- 29347766
TI - Correlations in eigenfunctions of quantum chaotic systems with sparse Hamiltonian
matrices.
AB - In most realistic models for quantum chaotic systems, the Hamiltonian matrices in
unperturbed bases have a sparse structure. We study correlations in
eigenfunctions of such systems and derive explicit expressions for some of the
correlation functions with respect to energy. The analytical results are tested
in several models by numerical simulations. Some applications are discussed for a
relation between transition probabilities and for expectation values of some
local observables.
PMID- 29347767
TI - Sampling of temporal networks: Methods and biases.
AB - Temporal networks have been increasingly used to model a diversity of systems
that evolve in time; for example, human contact structures over which dynamic
processes such as epidemics take place. A fundamental aspect of real-life
networks is that they are sampled within temporal and spatial frames.
Furthermore, one might wish to subsample networks to reduce their size for better
visualization or to perform computationally intensive simulations. The sampling
method may affect the network structure and thus caution is necessary to
generalize results based on samples. In this paper, we study four sampling
strategies applied to a variety of real-life temporal networks. We quantify the
biases generated by each sampling strategy on a number of relevant statistics
such as link activity, temporal paths and epidemic spread. We find that some
biases are common in a variety of networks and statistics, but one strategy,
uniform sampling of nodes, shows improved performance in most scenarios. Given
the particularities of temporal network data and the variety of network
structures, we recommend that the choice of sampling methods be problem oriented
to minimize the potential biases for the specific research questions on hand. Our
results help researchers to better design network data collection protocols and
to understand the limitations of sampled temporal network data.
PMID- 29347768
TI - Zealotry effects on opinion dynamics in the adaptive voter model.
AB - The adaptive voter model has been widely studied as a conceptual model for
opinion formation processes on time-evolving social networks. Past studies on the
effect of zealots, i.e., nodes aiming to spread their fixed opinion throughout
the system, only considered the voter model on a static network. Here we extend
the study of zealotry to the case of an adaptive network topology co-evolving
with the state of the nodes and investigate opinion spreading induced by zealots
depending on their initial density and connectedness. Numerical simulations
reveal that below the fragmentation threshold a low density of zealots is
sufficient to spread their opinion to the whole network. Beyond the transition
point, zealots must exhibit an increased degree as compared to ordinary nodes for
an efficient spreading of their opinion. We verify the numerical findings using a
mean-field approximation of the model yielding a low-dimensional set of coupled
ordinary differential equations. Our results imply that the spreading of the
zealots' opinion in the adaptive voter model is strongly dependent on the link
rewiring probability and the average degree of normal nodes in comparison with
that of the zealots. In order to avoid a complete dominance of the zealots'
opinion, there are two possible strategies for the remaining nodes: adjusting the
probability of rewiring and/or the number of connections with other nodes,
respectively.
PMID- 29347769
TI - Physics behind the mechanical nucleosome positioning code.
AB - The positions along DNA molecules of nucleosomes, the most abundant DNA-protein
complexes in cells, are influenced by the sequence-dependent DNA mechanics and
geometry. This leads to the "nucleosome positioning code", a preference of
nucleosomes for certain sequence motives. Here we introduce a simplified model of
the nucleosome where a coarse-grained DNA molecule is frozen into an idealized
superhelical shape. We calculate the exact sequence preferences of our nucleosome
model and find it to reproduce qualitatively all the main features known to
influence nucleosome positions. Moreover, using well-controlled approximations to
this model allows us to come to a detailed understanding of the physics behind
the sequence preferences of nucleosomes.
PMID- 29347770
TI - Viscosity of two-dimensional strongly coupled dusty plasma modified by a
perpendicular magnetic field.
AB - Transport properties of two-dimensional (2D) strongly coupled dusty plasmas have
been investigated in detail, but never for viscosity with a strong perpendicular
magnetic field; here, we examine this scenario using Langevin dynamics
simulations of 2D liquids with a binary Yukawa interparticle interaction. The
shear viscosity eta of 2D liquid dusty plasma is estimated from the simulation
data using the Green-Kubo relation, which is the integration of the shear stress
autocorrelation function. It is found that, when a perpendicular magnetic field
is applied, the shear viscosity of 2D liquid dusty plasma is modified
substantially. When the magnetic field is increased, its viscosity increases at
low temperatures, while at high temperatures its viscosity diminishes. It is
determined that these different variational trends of eta arise from the
different behaviors of the kinetic and potential parts of the shear stress under
external magnetic fields.
PMID- 29347771
TI - Hierarchy measurement for modeling network dynamics under directed attacks.
AB - A fundamental issue in the dynamics of complex systems is the resilience of the
network in response to targeted attacks. This paper explores the local dynamics
of the network attack process by investigating the order of removal of the nodes
that have maximal degree, and shows that this dynamic network response can be
predicted from the graph's initial connectivity. We demonstrate numerically that
the maximal degree M(tau) of the network at time step tau decays exponentially
with tau via a topology-dependent exponent. Moreover, the order in which sites
are removed can be approximated by considering the network's "hierarchy" function
h, which measures for each node V_{i} how many of its initial nearest neighbors
have lower degree versus those that have a higher one. Finally, we show that the
exponents we identified for the attack dynamics are related to the exponential
behavior of spreading activation dynamics. The results suggest that the function
h, which has both local and global properties, is a novel nodal measurement for
network dynamics and structure.
PMID- 29347772
TI - Energy nonequipartition in gas mixtures of inelastic rough hard spheres: The
tracer limit.
AB - The dynamical properties of a tracer or impurity particle immersed in a host gas
of inelastic and rough hard spheres in the homogeneous cooling state is studied.
Specifically, the breakdown of energy equipartition as characterized by the
tracer/host ratios of translational and rotational temperatures is analyzed by
exploring a wide spectrum of values of the control parameters of the system
(masses, moments of inertia, sizes, and coefficients of restitution). Three
complementary approaches are considered. On the theoretical side, the Boltzmann
and Boltzmann-Lorentz equations (both assuming the molecular chaos ansatz) are
solved by means of a multitemperature Maxwellian approximation for the velocity
distribution functions. This allows us to obtain explicit analytical expressions
for the temperature ratios. On the computational side, two different techniques
are used. First, the kinetic equations are numerically solved by the direct
simulation Monte Carlo (DSMC) method. Second, molecular dynamics simulations for
dilute gases are performed. Comparison between theory and simulations shows a
general good agreement. This means that (i) the impact of the molecular chaos
ansatz on the temperature ratios is not significant (except at high
inelasticities and/or big impurities) and (ii) the simple Maxwellian
approximation yields quite reliable predictions.
PMID- 29347773
TI - Hypothesis testing of scientific Monte Carlo calculations.
AB - The steadily increasing size of scientific Monte Carlo simulations and the desire
for robust, correct, and reproducible results necessitates rigorous testing
procedures for scientific simulations in order to detect numerical problems and
programming bugs. However, the testing paradigms developed for deterministic
algorithms have proven to be ill suited for stochastic algorithms. In this paper
we demonstrate explicitly how the technique of statistical hypothesis testing,
which is in wide use in other fields of science, can be used to devise automatic
and reliable tests for Monte Carlo methods, and we show that these tests are able
to detect some of the common problems encountered in stochastic scientific
simulations. We argue that hypothesis testing should become part of the standard
testing toolkit for scientific simulations.
PMID- 29347774
TI - Local and global avalanches in a two-dimensional sheared granular medium.
AB - We present the experimental and numerical studies of a two-dimensional sheared
amorphous material composed of bidisperse photoelastic disks. We analyze the
statistics of avalanches during shear including the local and global fluctuations
in energy and changes in particle positions and orientations. We find scale-free
distributions for these global and local avalanches denoted by power laws whose
cutoffs vary with interparticle friction and packing fraction. Different
exponents are found for these power laws depending on the quantity from which
variations are extracted. An asymmetry in time of the avalanche shapes is
evidenced along with the fact that avalanches are mainly triggered by the shear
bands. A simple relation independent of the intensity is found between the number
of local avalanches and the global avalanches they form. We also compare these
experimental and numerical results for both local and global fluctuations to
predictions from mean-field and depinning theories.
PMID- 29347775
TI - Mode locking in systems of globally coupled phase oscillators.
AB - We investigate the dynamics of a Kuramoto-type system of globally coupled phase
oscillators with equidistant natural frequencies and a coupling strength below
the synchronization threshold. It turns out that in such cases one can observe a
stable regime of sharp pulses in the mean field amplitude with a pulsation
frequency given by spacing of the natural frequencies. This resembles a process
known as mode locking in lasers and relies on the emergence of a phase relation
induced by the nonlinear coupling. We discuss the role of the first and second
harmonics in the phase-interaction function for the stability of the pulsations
and present various bifurcating dynamical regimes such as periodically and
chaotically modulated mode locking, transitions to phase turbulence, and
intermittency. Moreover, we study the role of the system size and show that in
certain cases one can observe type II supertransients, where the system reaches
the globally stable mode-locking solution only after an exponentially long
transient of phase turbulence.
PMID- 29347776
TI - Entropy, specific heat, susceptibility, and Rushbrooke inequality in percolation.
AB - We investigate percolation, a probabilistic model for continuous phase
transition, on square and weighted planar stochastic lattices. In its thermal
counterpart, entropy is minimally low where order parameter (OP) is maximally
high and vice versa. In addition, specific heat, OP, and susceptibility exhibit
power law when approaching the critical point and the corresponding critical
exponents alpha,beta,gamma respectably obey the Rushbrooke inequality (RI)
alpha+2beta+gamma>=2. Their analogs in percolation, however, remain elusive. We
define entropy and specific heat and redefine susceptibility for percolation and
show that they behave exactly in the same way as their thermal counterpart. We
also show that RI holds for both the lattices albeit they belong to different
universality classes.
PMID- 29347777
TI - Power output for a nonlinear Brownian machine.
AB - We propose a method that makes use of the nonlinear properties of some
hypothetical microscopic solid material as the working substance for a
microscopic machine. The protocols used are simple (step and elliptic) and allow
us to obtain the work and heat exchanged between machine and reservoirs. We
calculate the work for a nonlinear single-particle machine that can be treated
perturbingly. We obtain the instantaneous work and heat for the machine
undergoing cycles that mimic the Carnot and multireservoir protocols. The work
calculations are then extended to high values of the nonlinear parameter yielding
the quasistatic limit, which is verified numerically. The model we propose is
fluctuation driven and we can study in detail its thermostatistics, namely, the
work distribution both per cycle and instantaneous and the corresponding
fluctuation relations.
PMID- 29347778
TI - Forces in inhomogeneous open active-particle systems.
AB - We study the force that noninteracting pointlike active particles apply to a
symmetric inert object in the presence of a gradient of activity and particle
sources and sinks. We consider two simple patterns of sources and sinks that are
common in biological systems. We analytically solve a one-dimensional model
designed to emulate higher-dimensional systems, and study a two-dimensional model
by numerical simulations. We specify when the particle flux due to the creation
and annihilation of particles can act to smooth the density profile that is
induced by a gradient in the velocity of the active particles, and find the net
resultant force due to both the gradient in activity and the particle flux. These
results are compared qualitatively to observations of nuclear motion inside the
oocyte, that is driven by a gradient in activity of actin-coated vesicles.
PMID- 29347779
TI - Effective viscosity of a suspension of flagellar-beating microswimmers: Three
dimensional modeling.
AB - Micro-organisms usually can swim in their liquid environment by flagellar or
ciliary beating. In this numerical work, we analyze the influence of flagellar
beating on the orbits of a swimming cell in a shear flow. We also calculate the
effect of the flagellar beating on the rheology of a dilute suspension of
microswimmers. A three-dimensional model is proposed for Chlamydomonas
Reinhardtii swimming with a breaststroke-like beating of two anterior flagella
modeled by two counter-rotating fore beads. The active swimmer model reveals
unusual angular orbits in a linear shear flow. Namely, the swimmer sustains
orientations transiently across the flow. Such behavior is a result of the
interplay between shear flow and the swimmer's periodic beating motion of
flagella, which exert internal torques on the cell body. This peculiar behavior
has some significant consequences on the rheological properties of the
suspension. We calculate Einstein's viscosity of the suspension composed of such
isolated modeled microswimmers (dilute case) in a shear flow. We use numerical
simulations based on a Rotne-Prager-like approximation for hydrodynamic
interaction between simplified flagella and the cell body. The results show an
increased intrinsic viscosity for active swimmer suspensions in comparison to
nonactive ones as well as a shear thinning behavior in accordance with previous
experimental measurements [Phys. Rev. Lett. 104, 098102
(2010)10.1103/PhysRevLett.104.098102].
PMID- 29347780
TI - Stochastic thermodynamics for a periodically driven single-particle pump.
AB - We present the stochastic thermodynamic analysis of a time-periodic single
particle pump, including explicit results for flux, thermodynamic force, entropy
production, work, heat, and efficiency. These results are valid far from
equilibrium. The deviations from the linear (Onsager) regime are discussed.
PMID- 29347781
TI - Flow properties and hydrodynamic interactions of rigid spherical microswimmers.
AB - We analyze a minimal model for a rigid spherical microswimmer and explore the
consequences of its extended surface on the interplay between its self-propulsion
and flow properties. The model is the first order representation of
microswimmers, such as bacteria and algae, with rigid bodies and flexible
propelling appendages. The flow field of such a microswimmer at finite distances
significantly differs from that of a point-force (Stokeslet) dipole. For a
suspension of microswimmers, we derive the grand mobility matrix that connects
the motion of an individual swimmer to the active and passive forces and torques
acting on all the swimmers. Our investigation of the mobility tensors reveals
that hydrodynamic interactions among rigid-bodied microswimmers differ
considerably from those among the corresponding point-force dipoles. Our results
are relevant for the study of collective behavior of hydrodynamically interacting
microswimmers by means of Stokesian dynamics simulations at moderate
concentrations.
PMID- 29347782
TI - Stationary uphill currents in locally perturbed zero-range processes.
AB - Uphill currents are observed when mass diffuses in the direction of the density
gradient. We study this phenomenon in stationary conditions in the framework of
locally perturbed one-dimensional zero range processes (ZRPs). We show that the
onset of currents flowing from the reservoir with smaller density to the one with
larger density can be caused by a local asymmetry in the hopping rates on a
single site at the center of the lattice. For fixed injection rates at the
boundaries, we prove that a suitable tuning of the asymmetry in the bulk may
induce uphill diffusion at arbitrarily large, finite volumes. We also deduce
heuristically the hydrodynamic behavior of the model and connect the local
asymmetry characterizing the ZRP dynamics to a matching condition relevant for
the macroscopic problem.
PMID- 29347783
TI - Subjamming transition in binary sphere mixtures.
AB - We study the influence of particle-size asymmetry on structural evolution of
randomly jammed binary sphere mixtures with varying large-sphere and small-sphere
composition. Simulations of jammed packings are used to assess the transition
from large-sphere dominant to small-sphere dominant mixtures. For weakly
asymmetric particle sizes, packing properties evolve smoothly, but not
monotonically, with increasing small-sphere composition, f. Our simulations
reveal that at high values of ratio alpha of large- to small-sphere radii
(alpha>=alpha_{c}~5.75), evolution of structural properties, such as packing
density, fraction of jammed spheres, and contact statistics with f, exhibit
features that suggest a sharp transition, either through discontinuities in
structural measures or their derivatives. We argue that this behavior is related
to the singular, composition dependence of close-packing fraction predicted in
infinite aspect ratio mixtures alpha->infinity by the Furnas model, but occurring
for finite valued range of alpha above a critical value, alpha_{c}~5.75. The
existence of a sharp transition from small- to large-f values for
alpha>=alpha_{c} can be attributed to the existence of a subjamming transition of
small spheres within the interstices of jammed large spheres along the line of
compositions f_{sub}(alpha). We argue that the critical value of finite-size
asymmetry alpha_{c}?5.75 is consistent with the geometric criterion for the
transmission of small-sphere contacts between neighboring tetrahedrally close
packed interstices of large spheres, facilitating a cooperative subjamming
transition of small spheres confined within the disjoint volumes.
PMID- 29347784
TI - Parametric pulse amplification by acoustic quasimodes in electron-positron
plasma.
AB - In a recent paper, M. R. Edwards, N. J. Fisch, and J. M. Mikhailova [Phys. Rev.
Lett. 116, 015004 (2016)PRLTAO0031-900710.1103/PhysRevLett.116.015004] reported
that in electron-positron plasma stimulated Brillouin scattering is drastically
enhanced, while stimulated Raman scattering is completely absent. However, when
theory was compared to particle-in-cell (PIC) simulations, a discrepancy by at
least a factor four appeared. Authors correctly argued that the disparity might
be due to the fluid approximation of the low-frequency mode. They noted that a
more precise analytic description of the acoustic resonance requires a kinetic
approach, which was beyond the scope of the mentioned paper. Here we deliver the
so-far-missing kinetic calculation. It shows quite good agreement with the PIC
simulations presented in the above-mentioned paper by Edwards et al. The
principal result of enhancement of Brillouin scattering and absence of Raman
scattering remains valid. The Brillouin enhancement factors depend on electron
temperature and background particle density. These dependencies as well as the
transition to the well-known behavior of electron-ion plasma are discussed. It is
also shown that pulse amplification in electron-positron plasma crosses over to
the strong-coupling regime when the pump amplitude becomes large. Then, the fluid
approximation becomes acceptable again.
PMID- 29347785
TI - Discontinuous fluidization transition in time-correlated assemblies of actively
deforming particles.
AB - Tracking experiments in dense biological tissues reveal a diversity of sources
for local energy injection at the cell scale. The effect of cell motility has
been largely studied, but much less is known about the effect of the observed
volume fluctuations of individual cells. We consider a microscopic model of
"actively deforming" particles where local fluctuations of the particle size
constitute a unique source of motion. We demonstrate that collective motion can
emerge under the sole influence of such active volume fluctuations. We interpret
the onset of diffusive motion as a nonequilibrium first-order phase transition,
which arises at a well-defined amplitude of self-deformation. This behavior
contrasts with the glassy dynamics produced by self-propulsion, but resembles the
mechanical response of soft solids under mechanical deformation. It thus
constitutes an example of an active yielding transition.
PMID- 29347786
TI - Dynamics of a magnetic active Brownian particle under a uniform magnetic field.
AB - The dynamics of a magnetic active Brownian particle undergoing three-dimensional
Brownian motion, both translation and rotation, under the influence of a uniform
magnetic field is investigated. The particle self-propels at a constant speed
along its magnetic dipole moment, which reorients due to the interplay between
Brownian and magnetic torques, quantified by the Langevin parameter alpha. In
this work, the time-dependent active diffusivity and the crossover time
(tau^{cross})-from ballistic to diffusive regimes-are calculated through the time
dependent correlation function of the fluctuations of the propulsion direction.
The results reveal that, for any value of alpha, the particle undergoes a
directional (or ballistic) propulsive motion at very short times (t?tau^{cross}).
In this regime, the correlation function decreases linearly with time, and the
active diffusivity increases with it. It the opposite time limit (t?tau^{cross}),
the particle moves in a purely diffusive regime with a correlation function that
decays asymptotically to zero and an active diffusivity that reaches a constant
value equal to the long-time active diffusivity of the particle. As expected in
the absence of a magnetic field (alpha=0), the crossover time is equal to the
characteristic time scale for rotational diffusion, tau_{rot}. In the presence of
a magnetic field (alpha>0), the correlation function, the active diffusivity, and
the crossover time decrease with increasing alpha. The magnetic field regulates
the regimes of propulsion of the particle. Here, the field reduces the period of
time at which the active particle undergoes a directional motion. Consequently,
the active particle rapidly reaches a diffusive regime at tau^{cross}?tau_{rot}.
In the limit of weak fields (alpha?1), the crossover time decreases quadratically
with alpha, while in the limit of strong fields (alpha?1) it decays
asymptotically as alpha^{-1}. The results are in excellent agreement with those
obtained by Brownian dynamics simulations.
PMID- 29347787
TI - Direct determination approach for the multifractal detrending moving average
analysis.
AB - In the canonical framework, we propose an alternative approach for the
multifractal analysis based on the detrending moving average method (MF-DMA). We
define a canonical measure such that the multifractal mass exponent tau(q) is
related to the partition function and the multifractal spectrum f(alpha) can be
directly determined. The performances of the direct determination approach and
the traditional approach of the MF-DMA are compared based on three synthetic
multifractal and monofractal measures generated from the one-dimensional p-model,
the two-dimensional p-model, and the fractional Brownian motions. We find that
both approaches have comparable performances to unveil the fractal and
multifractal nature. In other words, without loss of accuracy, the multifractal
spectrum f(alpha) can be directly determined using the new approach with less
computation cost. We also apply the new MF-DMA approach to the volatility time
series of stock prices and confirm the presence of multifractality.
PMID- 29347788
TI - Particle transport across a channel via an oscillating potential.
AB - Membrane protein transporters alternate their substrate-binding sites between the
extracellular and cytosolic side of the membrane according to the alternating
access mechanism. Inspired by this intriguing mechanism devised by nature, we
study particle transport through a channel coupled with an energy well that
oscillates its position between the two entrances of the channel. We optimize
particle transport across the channel by adjusting the oscillation frequency. At
the optimal oscillation frequency, the translocation rate through the channel is
a hundred times higher with respect to free diffusion across the channel. Our
findings reveal the effect of time-dependent potentials on particle transport
across a channel and will be relevant for membrane transport and microfluidics
application.
PMID- 29347789
TI - Optimal paths on the road network as directed polymers.
AB - We analyze the statistics of the shortest and fastest paths on the road network
between randomly sampled end points. We find that, to a good approximation, the
optimal paths can be described as directed polymers in a disordered medium, which
belong to the Kardar-Parisi-Zhang universality class of interface roughening.
Comparing the scaling behavior of our data with simulations of directed polymers
and previous theoretical results, we are able to point out the few
characteristics of the road network that are relevant to the large-scale
statistics of optimal paths. Indeed, we show that the local structure is akin to
a disordered environment with a power-law distribution which become less
important at large scales where long-ranged correlations in the network control
the scaling behavior of the optimal paths.
PMID- 29347790
TI - Finite connected components in infinite directed and multiplex networks with
arbitrary degree distributions.
AB - This work presents exact expressions for size distributions of weak and
multilayer connected components in two generalizations of the configuration
model: networks with directed edges and multiplex networks with an arbitrary
number of layers. The expressions are computable in a polynomial time and, under
some restrictions, are tractable from the asymptotic theory point of view. If
first partial moments of the degree distribution are finite, the size
distribution for two-layer connected components in multiplex networks exhibits an
exponent -3/2 in the critical regime, whereas the size distribution of weakly
connected components in directed networks exhibits two critical exponents -1/2
and -3/2.
PMID- 29347791
TI - Beyond the faster-is-slower effect.
AB - The "faster-is-slower" effect arises when crowded people push each other to
escape through an exit during an emergency situation. As individuals push harder,
a statistical slowing down in the evacuation time can be achieved. The slowing
down is caused by the presence of small groups of pedestrians (say, a small human
cluster) that temporarily block the way out when trying to leave the room. The
pressure on the pedestrians belonging to this blocking cluster increases for
increasing anxiety levels and/or a larger number of individuals trying to leave
the room through the same door. Our investigation shows, however, that very high
pressures alter the dynamics in the blocking cluster and, thus, change the
statistics of the time delays along the escaping process. A reduction in the long
lasting delays can be acknowledged, while the overall evacuation performance
improves. We present results on this phenomenon taking place beyond the faster-is
slower regime.
PMID- 29347792
TI - Resonances in a periodically driven bosonic system.
AB - Periodically driven systems are a common topic in modern physics. In optical
lattices specifically, driving is at the origin of many interesting phenomena.
However, energy is not conserved in driven systems, and under periodic driving,
heating of a system is a real concern. In an effort to better understand this
phenomenon, the heating of single-band systems has been studied, with a focus on
disorder- and interaction-induced effects, such as many-body localization.
Nevertheless, driven systems occur in a much wider context than this, leaving
room for further research. Here, we fill this gap by studying a noninteracting
model, characterized by discrete, periodically spaced energy levels that are
unbounded from above. We couple these energy levels resonantly through a periodic
drive, and discuss the heating dynamics of this system as a function of the
driving protocol. In this way, we show that a combination of stimulated emission
and absorption causes the presence of resonant stable states. This will serve to
elucidate the conditions under which resonant driving causes heating in quantum
systems.
PMID- 29347793
TI - Instabilities of an annulus flow between rotating cylinders in a helical magnetic
field.
AB - The stabilities of an annulus flow between the rotating inner and outer cylinders
with an external helical magnetic field are studied by using the quasistatic
approximation. It is shown numerically that for the spiral base flow with a zero
axial pressure gradient, the helical magnetic field yields a helical traveling
wave at a critical Reynolds number. This wave mode is revealed to be the most
unstable mode by linear stability analysis. At higher Reynolds numbers, the first
wave mode is superposed by a second antisymmetric helical wave mode, which
travels with a higher phase velocity than the first mode. When the Reynolds
number is increased further, the flow becomes turbulent, but the key features of
the flow structure are still dominated by the first and the second wave modes.
Furthermore, when a finite axial pressure gradient is applied to guarantee a zero
axial flow rate, the annulus flow is found to be more unstable than the case with
zero axial pressure gradient.
PMID- 29347794
TI - Publisher's Note: Discovering phases, phase transitions, and crossovers through
unsupervised machine learning: A critical examination [Phys. Rev. E 95, 062122
(2017)].
AB - This corrects the article DOI: 10.1103/PhysRevE.95.062122.
PMID- 29347795
TI - Kibble-Zurek scaling of the irreversible entropy production.
AB - If a system is driven at finite rate through a phase transition by varying an
intensive parameter, the order parameter shatters into finite domains. The Kibble
Zurek mechanism predicts the typical size of these domains, which are governed
only by the rate of driving and the spatial and dynamical critical exponents. We
show that also the irreversible entropy production fulfills a universal behavior,
which however is determined by an additional critical exponent corresponding to
the intensive control parameter. Our universal prediction is numerically tested
in two systems exhibiting noise-induced phase transitions.
PMID- 29347796
TI - Headward growth and branching in subterranean channels.
AB - We investigate the erosive growth of channels in a thin subsurface sedimentary
layer driven by hydrodynamic drag toward understanding subterranean networks and
their relation to river networks charged by ground water. Building on a model
based on experimental observations of fluid-driven evolution of bed porosity, we
focus on the characteristics of the channel growth and their bifurcations in a
horizontal rectangular domain subject to various fluid source and sink
distributions. We find that the erosion front between low- and high-porosity
regions becomes unstable, giving rise to branched channel networks, depending on
the spatial fluctuations of the fluid flow near the front and the degree to which
the flow is above the erodibility threshold of the medium. Focusing on the growth
of a network starting from a single channel, and by identifying the channel heads
and their branch points, we find that the number of branches increases
sublinearly and is affected by the source distribution. The mean angles between
branches are found to be systematically lower than river networks in humid
climates and depend on the domain geometry.
PMID- 29347797
TI - Relaxation, thermalization, and Markovian dynamics of two spins coupled to a spin
bath.
AB - It is shown that by fitting a Markovian quantum master equation to the numerical
solution of the time-dependent Schrodinger equation of a system of two spin-1/2
particles interacting with a bath of up to 34 spin-1/2 particles, the former can
describe the dynamics of the two-spin system rather well. The fitting procedure
that yields this Markovian quantum master equation accounts for all non-Markovian
effects in as much the general structure of this equation allows and yields a
description that is incompatible with the Lindblad equation.
PMID- 29347798
TI - Dispersion of the intrinsic neuronal periods affects the relationship of the
entrainment range to the coupling strength in the suprachiasmatic nucleus.
AB - Living beings on the Earth are subjected to and entrained (synchronized) to the
natural 24-h light-dark cycle. Interestingly, they can also be entrained to an
external artificial cycle of non-24-h periods. The range of these periods is
called the entrainment range and it differs among species. In mammals, the
entrainment range is regulated by a main clock located in the suprachiasmatic
nucleus (SCN) which is composed of 10 000 neurons in the brain. Previous works
have found that the entrainment range depends on the cellular coupling strength
in the SCN. In particular, the entrainment range decreases with the increase of
the cellular coupling strength, provided that all the neuronal oscillators are
identical. However, the SCN neurons differ in the intrinsic periods that follow a
normal distribution in a range from 22 to 28 h. In the present study, taking the
dispersion of the intrinsic neuronal periods into account, we examined the
relationship between the entrainment range and the coupling strength. Results
from numerical simulations and theoretical analyses both show that the
relationship is altered to be paraboliclike if the intrinsic neuronal periods are
nonidentical, and the maximal entrainment range is obtained with a suitable
coupling strength. Our results shed light on the role of the cellular coupling in
the entrainment ability of the SCN network.
PMID- 29347799
TI - Confinement effects in premelting dynamics.
AB - We examine the effects of confinement on the dynamics of premelted films driven
by thermomolecular pressure gradients. Our approach is to modify a well-studied
setting in which the thermomolecular pressure gradient is driven by a temperature
gradient parallel to an interfacially premelted elastic wall. The modification
treats the increase in viscosity associated with the thinning of films, studied
in a wide variety of materials, using a power law and we examine the consequent
evolution of the confining elastic wall. We treat (1) a range of interactions
that are known to underlie interfacial premelting and (2) a constant temperature
gradient wherein the thermomolecular pressure gradient is a constant. The
difference between the cases with and without the proximity effect arises in the
volume flux of premelted liquid. The proximity effect increases the viscosity as
the film thickness decreases thereby requiring the thermomolecular pressure
driven flux to be accommodated at higher temperatures where the premelted film
thickness is the largest. Implications for experiment and observations of frost
heave are discussed.
PMID- 29347800
TI - Roughness-enhanced transport in a tilted ratchet driven by Levy noise.
AB - The enhanced transport of particles by roughness in a tilted rough ratchet
potential subject to a Levy noise is investigated in this paper. Due to the
roughness, the transport process exhibits quite different properties compared to
the smooth case. We find that the roughness on the potential wall functions like
a ladder to provide the convenience for particles to climb up but hinder them to
slide down. The mean first passage time from one well to its right adjacent well
and the mean velocity are, respectively, calculated versus the roughness, the
external force, and the Levy stability index. Our results show that the roughness
is able to induce an enhancement on the mean velocity of particles and accelerate
the barrier crossing process. The general conditions require a small external
force and a small Levy stability index. We find that with increasing external
forces, the enhancement areas of roughness and Levy stability index both shrink.
However, for the Levy stability index within the enhancement area, its increase
will enlarge the enhancement area of roughness. On the contrary, under the same
conditions we observe that for a Gaussian noise the roughness always reduces the
corresponding mean velocity which is very different from the case of Levy noise.
PMID- 29347801
TI - Erratum: Aging Wiener-Khinchin theorem and critical exponents of 1/f^{beta} noise
[Phys. Rev. E 94, 052130 (2016)].
AB - This corrects the article DOI: 10.1103/PhysRevE.94.052130.
PMID- 29347802
TI - Entropy production and volume contraction in thermostated Hamiltonian dynamics.
AB - Patra et al. [Int. J. Bifurcat. Chaos 26, 1650089 (2016)IJBEE40218
127410.1142/S0218127416500899] recently showed that the time-averaged rates of
entropy production and phase-space volume contraction are equal for several
different molecular dynamics methods used to simulate nonequilibrium steady
states in Hamiltonian systems with thermostated temperature gradients. This
equality is a plausible statistical analog of the second law of thermodynamics.
Here we show that those two rates are identically equal in a wide class of
methods in which the thermostat variables z are determined by ordinary
differential equations of motion (i.e., methods of the Nose-Hoover or integral
feedback control type). This class of methods is defined by three relatively
innocuous restrictions which are typically satisfied in methods of this type.
PMID- 29347803
TI - Experimental determination of phase transitions by means of configurational
entropies in finite Yukawa balls.
AB - The phase transition of finite Yukawa balls (ordered systems of microspheres in a
gaseous plasma environment) with less than 100 particles is studied
experimentally by means of configurational entropies. We have developed
cylindrical two- and three-particle-correlation functions to measure these
entropies for multiple cluster sizes over a wide temperature range. The cluster
temperature is finely tuned using a stochastic laser heating setup. It is shown
that the correlation functions give a detailed insight into the structural
properties of the cluster. The derived configurational entropies give a clear
indication of the transition temperature from a solid-like to a fluid-like state.
Comparing the transition temperatures of different sized clusters it is found
that the transition temperature increases with cluster size in general agreement
with theoretical predictions.
PMID- 29347804
TI - Active nematic gels as active relaxing solids.
AB - I propose a continuum theory for active nematic gels, defined as fluids or
suspensions of orientable rodlike objects endowed with active dynamics, that is
based on symmetry arguments and compatibility with thermodynamics. The starting
point is our recent theory that models (passive) nematic liquid crystals as
relaxing nematic elastomers. The interplay between viscoelastic response and
active dynamics of the microscopic constituents is naturally taken into account.
By contrast with standard theories, activity is not introduced as an additional
term of the stress tensor, but it is added as an external remodeling force that
competes with the passive relaxation dynamics and drags the system out of
equilibrium. In a simple one-dimensional channel geometry, we show that the
interaction between nonuniform nematic order and activity results in either a
spontaneous flow of particles or a self-organization into subchannels flowing in
opposite directions.
PMID- 29347805
TI - Spectral signatures of activity-dependent neural feedback in the corticothalamic
system.
AB - The modulation of neural quantities by presynaptic and postsynaptic activities
via local feedback processes is investigated by incorporating nonlinear phenomena
such as relative refractory period, synaptic enhancement, synaptic depression,
and habituation. This is done by introducing susceptibilities, which quantify the
response in either firing threshold or synaptic strength to unit change in either
presynaptic or postsynaptic activity. Effects on the power spectra are then
analyzed for a realistic corticothalamic model to determine the spectral
signatures of various nonlinear processes and to what extent these are distinct.
Depending on the feedback processes, there can be enhancements or reductions in
low-frequency and/or alpha power, splitting of the alpha resonance, and/or
appearance of new resonances at high frequencies. These features in the power
spectra allow processes to be fully distinguished where they are unique, or
partly distinguished if they are common to only a subset of feedbacks, and can
potentially be used to constrain the types, strengths, and dynamics of feedbacks
present.
PMID- 29347806
TI - Synchrony-induced modes of oscillation of a neural field model.
AB - We investigate the modes of oscillation of heterogeneous ring networks of
quadratic integrate-and-fire (QIF) neurons with nonlocal, space-dependent
coupling. Perturbations of the equilibrium state with a particular wave number
produce transient standing waves with a specific temporal frequency, analogously
to those in a tense string. In the neuronal network, the equilibrium corresponds
to a spatially homogeneous, asynchronous state. Perturbations of this state
excite the network's oscillatory modes, which reflect the interplay of episodes
of synchronous spiking with the excitatory-inhibitory spatial interactions. In
the thermodynamic limit, an exact low-dimensional neural field model describing
the macroscopic dynamics of the network is derived. This allows us to obtain
formulas for the Turing eigenvalues of the spatially homogeneous state and hence
to obtain its stability boundary. We find that the frequency of each Turing mode
depends on the corresponding Fourier coefficient of the synaptic pattern of
connectivity. The decay rate instead is identical for all oscillation modes as a
consequence of the heterogeneity-induced desynchronization of the neurons.
Finally, we numerically compute the spectrum of spatially inhomogeneous solutions
branching from the Turing bifurcation, showing that similar oscillatory modes
operate in neural bump states and are maintained away from onset.
PMID- 29347807
TI - Role of matrix behavior in compressive fracture of bovine cortical bone.
AB - In compressive fracture of dry plexiform bone, we examine the individual roles of
overall mean porosity, the connectivity of the porosity network, and the elastic
as well as the failure properties of the nonporous matrix, using a random spring
network model (RSNM). Porosity network structure is shown to reduce the
compressive strength by up to 30%. However, the load-bearing capacity increases
with an increase in either of the matrix properties-the elastic modulus or the
failure strain threshold. To validate the porosity-based RSNM model with
available experimental data, bone-specific failure strain thresholds for the
ideal matrix of similar elastic properties were estimated to be within 60% of
each other. Further, we observe the avalanche size exponents to be independent of
the bone-dependent parameters as well as the structure of the porosity network.
PMID- 29347808
TI - Thermodynamic theory of dislocation-enabled plasticity.
AB - The thermodynamic theory of dislocation-enabled plasticity is based on two
unconventional hypotheses. The first of these is that a system of dislocations,
driven by external forces and irreversibly exchanging heat with its environment,
must be characterized by a thermodynamically defined effective temperature that
is not the same as the ordinary temperature. The second hypothesis is that the
overwhelmingly dominant mechanism controlling plastic deformation is thermally
activated depinning of entangled pairs of dislocations. This paper consists of a
systematic reformulation of this theory followed by examples of its use in
analyses of experimentally observed phenomena including strain hardening, grain
size (Hall-Petch) effects, yielding transitions, and adiabatic shear banding.
PMID- 29347809
TI - Transient subdiffusion from an Ising environment.
AB - We introduce a model in which a particle performs a continuous-time random walk
(CTRW) coupled to an environment with Ising dynamics. The particle shows locally
varying diffusivity determined by the geometrical properties of the underlying
Ising environment, that is, the diffusivity depends on the size of the connected
area of spins pointing in the same direction. The model shows anomalous diffusion
when the Ising environment is at critical temperature. We show that any finite
scale introduced by a temperature different from the critical one, or a finite
size of the environment, cause subdiffusion only during a transient time. The
characteristic time, at which the system returns to normal diffusion after the
subdiffusive plateau depends on the limiting scale and on how close the
temperature is to criticality. The system also displays apparent ergodicity
breaking at intermediate time, while ergodicity breaking at longer time occurs
only under the idealized infinite environment at the critical temperature.
PMID- 29347810
TI - Plasma q-plate for generation and manipulation of intense optical vortices.
AB - An optical vortex is a light wave with a twisting wavefront around its
propagation axis and null intensity in the beam center. Its unique spatial
structure of field lends itself to a broad range of applications, including
optical communication, quantum information, superresolution microscopy, and
multidimensional manipulation of particles. However, accessible intensity of
optical vortices have been limited to material ionization threshold. This
limitation might be removed by using the plasma medium. Here we propose the
design of suitably magnetized plasmas which, functioning as a q-plate, leads to a
direct conversion from a high-intensity Gaussian beam into a twisted beam. A
circularly polarized laser beam in the plasma accumulates an azimuthal-angle
dependent phase shift and hence forms a twisting wavefront. Our three-dimensional
particle-in-cell simulations demonstrate extremely high-power conversion
efficiency. The plasma q-plate can work in a large range of frequencies spanning
from terahertz to the optical domain.
PMID- 29347811
TI - Orientation-shape coupling between liquid crystal and membrane through the
anchoring effect.
AB - We perform a series of Monte Carlo simulations on an interface between a liquid
crystal (LC) material in isotropic phase in its bulk and a surfactant membrane.
These two objects are simulated using coarse-grained molecular models. We
estimate physical properties of the membrane such as the interfacial tension and
the bending rigidity, focusing on the anchoring effects of the membrane on the
LC. According to our simulation results, when the strength of the homeotropic
anchoring denoted by the anchoring parameter xi is increased, the interfacial
tension decreases and the bending rigidity first increases in xi= 1) in UC with a
sensitivity of 81.8% and 85.8%, respectively, and a specificity of 100% for both.
Conclusions: FC was strongly associated with disease activity indices, serologic
markers, and endoscopic activity in patients with IBD. QPOCT can be used more
conveniently than ELISA to assess FC in clinical practice.
PMID- 29347814
TI - [Customization of hormonal contraception].
AB - In the last few years new oral contraceptives have been marketed showing a better
safety profile for women. They are the result of important changes made to the
old compounds. As far as the estrogenic component, with the aim of decreasing
side effects, the dose of ethinyl estradiol has been reduced and synthetic
estrogens have been replaced by natural estradiol, further improving the safety
profile. Also the progestin component in the last years has been changed in terms
of dose, endocrine and metabolic characteristics. Levonorgestrel is an androgenic
progestin, but now there is the possibility of choosing progestins without
androgenic effect (gestodene and desogestrel) or progestins with antiandrogenic
effect (cyproterone acetate, dienogest, drospirenone, chlormadinone acetate),
very useful in patients with hyperandrogenism. Some of these progestins, like
Drospirenone, represented the real held contributing, because of its
antimineralcorticoid action, to reduce an important side effect like fluid
retention; moreover there is the possibility to choose products with high
progestogen effect on endometrium (dienogest, nomegestrole acetate), resulting
very effective in women with abnormal uterine bleedings. Also the regimens of
administration have been changed, by shortening or eliminating the tablet-free
period; in this way the women may avoid premenstrual symptoms. The oral is not
the only route of administration, but today there are alternative routes like
transdermal, transvaginal, intrauterine and subcutaneous, reducing gastro
intestinal interferences and possible mistakes in pill intake.
PMID- 29347815
TI - Control over Electron-Phonon Interaction by Dirac Plasmon Engineering in the
Bi2Se3 Topological Insulator.
AB - Understanding the mutual interaction between electronic excitations and lattice
vibrations is key for understanding electronic transport and optoelectronic
phenomena. Dynamic manipulation of such interaction is elusive because it
requires varying the material composition on the atomic level. In turn, recent
studies on topological insulators (TIs) have revealed the coexistence of a strong
phonon resonance and topologically protected Dirac plasmon, both in the terahertz
(THz) frequency range. Here, using these intrinsic characteristics of TIs, we
demonstrate a new methodology for controlling electron-phonon interaction by
lithographically engineered Dirac surface plasmons in the Bi2Se3 TI. Through a
series of time-domain and time-resolved ultrafast THz measurements, we show that,
when the Dirac plasmon energy is less than the TI phonon energy, the electron
phonon coupling is trivial, exhibiting phonon broadening associated with Landau
damping. In contrast, when the Dirac plasmon energy exceeds that of the phonon
resonance, we observe suppressed electron-phonon interaction leading to
unexpected phonon stiffening. Time-dependent analysis of the Dirac plasmon
behavior, phonon broadening, and phonon stiffening reveals a transition between
the distinct dynamics corresponding to the two regimes as the Dirac plasmon
resonance moves across the TI phonon resonance, which demonstrates the capability
of Dirac plasmon control. Our results suggest that the engineering of Dirac
plasmons provides a new alternative for controlling the dynamic interaction
between Dirac carriers and phonons.
PMID- 29347816
TI - Pb-Activated Amine-Assisted Photocatalytic Hydrogen Evolution Reaction on Organic
Inorganic Perovskites.
AB - We report here the reaction mechanism for explicit aqueous solvent quantum
mechanics (QM) studies determining the energetics and reaction barriers for the
photocatalytic hydrogen evolution reaction (HER) on CH3NH3PbI3 surface. We find
that both the lead (Pb) atoms and the surface organic molecules play essential
roles, leading to a two-step Pb-activated amine-assisted (PbAAA) reaction
mechanism involving an intermediate lead hydride state. Both H of H2 product are
extracted from surface organic molecules, while two protons from the solution
migrate along water chains via the Grotthuss mechanism to replace the H in
organic molecule. We obtain a reaction barrier of 1.08 eV for photochemical
generation of H2 on CH3NH3PbI3 compared to 2.61 eV for the dark reaction. We
expect this HER mechanism can also apply to the other organic perovskites, but
the energy barriers and reaction rates may depend on the basicity of electrolyte
and intrinsic structures of perovskites.
PMID- 29347817
TI - Biochemical Basis of APOBEC3 Deoxycytidine Deaminase Activity on Diverse DNA
Substrates.
AB - The Apolipoprotein B mRNA editing complex (APOBEC) family of enzymes contains
single-stranded polynucleotide cytidine deaminases. These enzymes catalyze the
deamination of cytidine in RNA or single-stranded DNA, which forms uracil. From
this 11 member enzyme family in humans, the deamination of single-stranded DNA by
the seven APOBEC3 family members is considered here. The APOBEC3 family has many
roles, such as restricting endogenous and exogenous retrovirus replication and
retrotransposon insertion events and reducing DNA-induced inflammation. Similar
to other APOBEC family members, the APOBEC3 enzymes are a double-edged sword that
can catalyze deamination of cytosine in genomic DNA, which results in potential
genomic instability due to the many mutagenic fates of uracil in DNA. Here, we
discuss how these enzymes find their single-stranded DNA substrate in different
biological contexts such as during human immunodeficiency virus (HIV) proviral
DNA synthesis, retrotransposition of the LINE-1 element, and the "off-target"
genomic DNA substrate. The enzymes must be able to efficiently deaminate
transiently available single-stranded DNA during reverse transcription,
replication, or transcription. Specific biochemical characteristics promote
deamination in each situation to increase enzyme efficiency through processivity,
rapid enzyme cycling between substrates, or oligomerization state. The use of
biochemical data to clarify biological functions and alignment with cellular data
is discussed. Models to bridge knowledge from biochemical, structural, and single
molecule experiments are presented.
PMID- 29347818
TI - Far-Red Fluorescent Probe for Imaging of Vicinal Dithiol-Containing Proteins in
Living Cells Based on a pKa Shift Mechanism.
AB - Vicinal dithiol-containing proteins (VDPs) play fundamental roles in
intracellular redox homeostasis and are responsible for many diseases. In this
work, we report a far-red fluorescence turn-on probe MCAs for VDPs exploiting the
pKa shift of the imine functionality of the probe. MCAs is composed of a
merocyanine Schiff base as the fluorescent reporter and a cyclic 1,3,2
dithiarsenolane as the specific ligand for VDPs. The imine pKa of MCAs is 4.8,
and it exists predominantly in the Schiff base (SB) form at physiological pH. Due
to the absence of a resonating positive charge, it absorbs at a relatively short
wavelength and is essentially nonfluorescent. Upon selective binding to reduced
bovine serum albumin (rBSA, selected as the model protein), MCAs was brought from
aqueous media to the binding pockets of the protein, causing a large increase in
pKa value of MCAs (pKa = 7.1). As a result, an increase in the protonated Schiff
base (PSB) form of MCAs was observed at the physiological pH conditions, which in
turn leads to a bathochromically shifted chromophore (lambdaabs = 634 nm) and a
significant increase in fluorescence intensity (lambdaem = 657 nm)
simultaneously. Furthermore, molecular dynamics simulations indicate that the
salt bridges formed between the iminium in MCAs and the residues D72 and D517 in
rBSA resist the dissociation of proton from the probe, thus inducing an increase
of the pKa value. The proposed probe shows excellent sensitivity and specificity
toward VDPs over other proteins and biologically relevant species and has been
successfully applied for imaging of VDPs in living cells. We believe that the
present pKa shift switching strategy may facilitate the development of new
fluorescent probes that are useful for a wide range of applications.
PMID- 29347819
TI - Presence of Rigid Red Blood Cells in Blood Flow Interferes with the Vascular Wall
Adhesion of Leukocytes.
AB - The symptoms of many blood diseases can often be attributed to irregularities in
cellular dynamics produced by abnormalities in blood cells, particularly red
blood cells (RBCs). Contingent on the disease and its severity, RBCs can be
afflicted with increased membrane rigidity as seen in malaria and sickle cell
disease. Despite this understanding, little experimental work has been conducted
toward understanding the effect of RBC rigidity on cellular dynamics in
physiologic blood flow. Though many have computationally modeled complex blood
flow to postulate how RBC rigidity may disrupt normal hemodynamics, to date,
there lacks a clear understanding of how rigid RBCs affect the blood cell
segregation behavior in blood flow, known as margination, and the resulting
change in the adhesion of white blood cells (WBCs). In this work, we utilized an
in vitro blood flow model to examine how different RBC rigidities and volume
fractions of rigid RBCs impact cell margination and the downstream effect on
white blood cell (WBC) adhesion in blood flow. Healthy RBC membranes were
rigidified and reconstituted into whole blood and then perfused over activated
endothelial cells under physiologically relevant shear conditions. Rigid RBCs
were shown to reduce WBC adhesion by up to 80%, contingent on the RBC rigidity
and the fraction of treated RBCs present in blood flow. Furthermore, the RBC core
was found to be slightly expanded with the presence of rigid RBCs, by up to ~30%
in size fully composed of rigid RBCs. Overall, the obtained results demonstrate
an impact of RBC rigidity on cellular dynamics and WBC adhesion, which possibly
contributes to the pathological understanding of diseases characterized by
significant RBC rigidity.
PMID- 29347821
TI - Fluorescence and Excited-State Conformational Dynamics of the Orange Carotenoid
Protein.
AB - The orange carotenoid protein (OCP) mediates nonphotochemical quenching (NPQ)
mechanisms in cyanobacteria. A bound ketocarotenoid serves as a sensor of
midvisible light intensity and as a quencher of phycocyanobilin excitons in the
phycobilisome. The photochemical mechanism that triggers conversion of the
protein from a resting, orange state (OCPO) to an active, red state (OCPR) after
optical preparation of the S2 state of the carotenoid remains an open question.
We report here that the fluorescence spectrum and quantum yield of the bound
carotenoids in OCPO report important details of the motions that follow optical
preparation of the S2 state. The fluorescence spectra from OCPO preparations
containing 3'-hydroxyechinenone (3hECN) or canthaxanthin (CAN) are markedly
mirror asymmetric with respect to the absorption line shape and more than an
order of magnitude more intense than for carotenoids in solution. Further, 3hECN
exhibits a narrower fluorescence line shape and a larger quantum yield than CAN
because its excited-state motions are hindered by a hydrogen bonding interaction
between the 3'-hydroxyl group on its beta2 ring and Leu37 in the N-terminal
domain. These results show that large-amplitude motions of the carotenoid's beta2
cyclohexene ring and of the conjugated polyene backbone initiate photochemistry
in OCPO.
PMID- 29347825
TI - Increasing condom usage for African-American and hispanic young fathers in a
community based intervention.
AB - OBJECTIVES: This paper investigates a community-based intervention for young
fathers, FatherWorks, compared to care-as-usual, 24/7 Dads. We hypothesized that
utilizing the FatherWorks intervention (a 15 session parenting intervention, 13
session employment class, paid internship, case management, and access to
behavioral health services) will assist in readiness to use condoms and increase
condom usage, which may differ by race/ethnicity. METHODS: Eligible males (n =
328) were enrolled into a Randomized Control Trial. Participants were 15-24 years
old and had fathered one or more children with a female under the age of 21. A
survey was taken at baseline and at 15 weeks following the intervention. RESULTS:
Analyses of changes indicated that intervention participants improved from the
pre-contemplation stage of condom usage towards contemplation, and from
preparation to action. The pattern of improvement in the condom use stage of
change was different in African-American versus Hispanic participants. Changes in
condom use during last intercourse were not significant. CONCLUSIONS: Study
findings indicate that FatherWorks is successful in increasing the intent to use
condoms, with the effect manifesting differently in African-American and Hispanic
young fathers. Future work with minority fathers indicates a need for cultural
adaptation of the intervention.
PMID- 29347826
TI - Acceptability of HIV cure-related trials: the challenges for physicians and
people living with HIV (ANRS-APSEC).
AB - Essential HIV cure-related clinical trials (HCRCT) have a potentially high-risk
profile in terms of participants' health, which could hinder enrollment by people
living with HIV (PLWH) and healthcare professionals (HP). The ANRS-APSEC survey
is part of the IAS "Towards an HIV cure" initiative, which promotes
multidisciplinary research for a safe, affordable and scalable cure. The study
objectives were to understand the psychosocial mechanisms underlying PLWH and HP
viewpoints about future HCRCT. Six focus group discussions (three with PLWH (n =
21) and three with HP (n = 30)) were held in three French infectious disease
units. From these, three perspectives on HCRCT were identified. The first
involved beliefs and knowledge associating HCRCT with poorer health and quality
of life for PLWH. The second concerned perceptions of HCRCT as a biological and
epidemiological flashback to a situation when HIV infection was left
uncontrolled. The third was characterized by aspects of historical HIV culture
that embrace innovation.
PMID- 29347827
TI - Psychological well-being and adherence to antiretroviral therapy among
adolescents living with HIV in Zambia.
AB - Physical and psychosocial changes during adolescence could influence the
psychological well-being and adherence to antiretroviral therapy (ART) of
adolescents living with HIV. However, few studies have assessed these two
important issues in Zambia. This study aimed at addressing this gap by examining
adolescents' depressive symptoms and ART adherence. This was a mixed-methods
study conducted from April to July 2014. We recruited 200 adolescents, ages 15 to
19, who were already aware of their HIV status. We measured depressive symptoms
using the short form of the Center for Epidemiologic Studies Depression Scale,
and self-reported three-day adherence to ART. We performed logistic regression
analysis to identify factors associated with depressive symptoms and non
adherence to ART. For qualitative data, we examined challenges over ART adherence
using thematic analysis. Out of 190 adolescents, 25.3% showed high scores of
depressive symptoms. Factors associated with depressive symptoms were
unsatisfactory relationships with family (Adjusted Odds Ratio [AOR] 3.01; 95%
Confidence Interval [CI] 1.20-7.56); unsatisfactory relationships with health
workers (AOR 2.68; 95% CI 1.04-6.93); and experience of stigma (AOR 2.99; 95% CI
1.07-8.41). Of all participants, 94.2% were taking ART, but 28.3% were non
adherent. Factors associated with non-adherence to ART were loss of a mother (AOR
3.00; 95% CI 1.05-8.58) and lack of basic knowledge about HIV (AOR 3.25; 95% CI
1.43-7.40). Qualitative data identified the following challenges to ART
adherence: management of medication, physical reactions to medicine, and
psychosocial distress. The evidence suggests that depressive symptoms and non
adherence to ART were priority issues in late adolescence in Zambia. Health
workers should be aware of these issues, and the care and treatment services
should be tailored to respond to age-specific needs.
PMID- 29347828
TI - Change in HIV-related stigma in South Africa between 2004 and 2016: a cross
sectional community study.
AB - A critical component of an AIDS-free generation is to reduce HIV-related stigma.
Previous research predicted that stigma would decline over time with increased
contact with PLWH, understanding of the disease and availability of treatment.
The aim of the research was to explore change in stigma over a 12-year period, by
comparing data collected from two large cross-sectional samples from South
African communities in 2004 (before the roll-out of antiretroviral treatment
(ART)) and in 2016. Students recruited respondents according to criteria related
to age, gender, race and area of living. A survey assessing moral judgement and
interpersonal distance was used to assess personal and perceived community
stigma. Responses to ten identical items used in the 2004 and 2016 data
collection were compared. Personal stigma attached to HIV decreased significantly
over time, except in respect of having close contact with PLWH, such as dating
and befriending. Perceived community stigma remained high in all subgroups. It is
argued that perceived community stigma contributes to high levels of internalised
stigma among PLWH. Interventions should focus on helping PLWH to cope with
perceived stigma and strategies to address stereotyping, which contributes to
perceived community stigma.
PMID- 29347829
TI - Biofilm community structure and the associated drag penalties of a groomed
fouling release ship hull coating.
AB - Grooming is a proactive method to keep a ship's hull free of fouling. This
approach uses a frequent and gentle wiping of the hull surface to prevent the
recruitment of fouling organisms. A study was designed to compare the community
composition and the drag associated with biofilms formed on a groomed and
ungroomed fouling release coating. The groomed biofilms were dominated by members
of the Gammaproteobacteria and Alphaproteobacteria as well the diatoms Navicula,
Gomphonemopsis, Cocconeis, and Amphora. Ungroomed biofilms were characterized by
Phyllobacteriaceae, Xenococcaceae, Rhodobacteraceae, and the pennate diatoms
Cyclophora, Cocconeis, and Amphora. The drag forces associated with a groomed
biofilm (0.75 +/- 0.09 N) were significantly less than the ungroomed biofilm
(1.09 +/- 0.06 N). Knowledge gained from this study has helped the design of
additional testing which will improve grooming tool design, minimizing the growth
of biofilms and thus lowering the frictional drag forces associated with groomed
surfaces.
PMID- 29347830
TI - An OMIC biomarker detection algorithm TriVote and its application in methylomic
biomarker detection.
AB - AIM: Transcriptomic and methylomic patterns represent two major OMIC data sources
impacted by both inheritable genetic information and environmental factors, and
have been widely used as disease diagnosis and prognosis biomarkers. MATERIALS &
METHODS: Modern transcriptomic and methylomic profiling technologies detect the
status of tens of thousands or even millions of probing residues in the human
genome, and introduce a major computational challenge for the existing feature
selection algorithms. This study proposes a three-step feature selection
algorithm, TriVote, to detect a subset of transcriptomic or methylomic residues
with highly accurate binary classification performance. RESULTS & CONCLUSION:
TriVote outperforms both filter and wrapper feature selection algorithms with
both higher classification accuracy and smaller feature number on 17
transcriptomes and two methylomes. Biological functions of the methylome
biomarkers detected by TriVote were discussed for their disease associations. An
easy-to-use Python package is also released to facilitate the further
applications.
PMID- 29347831
TI - Racial/ethnic disparities in human papillomavirus vaccination initiation and
completion among U.S. women in the post-Affordable Care Act era.
AB - OBJECTIVE: To ascertain the magnitude and potential mechanisms of racial/ethnic
disparities in initiating and completing the 3-dose human papillomavirus (HPV)
vaccine among U.S. women in the post-Affordable Care Act era. DESIGN: Using 2015
National Health Interview Survey data, we used logistic regression to estimate
odds ratios (OR) and 95% confidence intervals (CI) for the association between
race/ethnicity and HPV vaccination initiation and completion among black, Latina,
Asian, and white U.S. women aged 18-31 years, adjusting for age and geographic
region. We also examined the role of socioeconomic and health care factors in
potentially explaining racial/ethnic disparities in HPV vaccine uptake and
stratified our analyses by age (ages 18-22 and 23-31 years). RESULTS: The
prevalence of HPV vaccination initiation and completion among U.S. women aged 18
31 years overall was 35.4% and 22.7%, respectively. We observed no statistically
significant difference in the odds of HPV vaccination initiation or completion by
race/ethnicity among women aged 18-22 years, adjusting for age and geographic
region. Among women aged 23-31 years, Latina ([odds ratio=] 0.59; [95% confidence
interval:] 0.47, 0.76) and Asian (0.51; 0.34, 0.75) women had significantly lower
adjusted odds of initiating HPV vaccination compared to white women. Further,
relative to white women, black (0.46; 0.32, 0.67), Latina (0.45; 0.32, 0.64), and
Asian (0.46; 0.28, 0.78) women had significantly lower adjusted odds of
completing HPV vaccination. Adding socioeconomic factors to the models attenuated
the HPV vaccination initiation adjusted odds ratios for Latina vs. white women
and the HPV vaccination completion adjusted odds ratios for both black and Latina
vs. white women. The inclusion of health care factors into the models did not
further attenuate these odds ratios. CONCLUSION: Policies and programs that
promote socioeconomic equity may mitigate HPV vaccination disparities between
black and Latina women and white women. Additional research is needed to identify
the drivers of HPV vaccination disparities between subgroups of Asian women and
white women.
PMID- 29347832
TI - Wire Placement in the Sustentaculum Tali Using a 2D Projection-Based Software
Application for Mobile C-Arms: Cadaveric Study.
AB - BACKGROUND: Indirect screw fixation of the sustentaculum tali in the lateral
medial direction can be challenging due to the complex calcaneal anatomy. A novel
2-dimensional (2D) projection-based software application detects Kirschner wires
(K-wires) and visualizes their intended direction as a colored trajectory. The
aim of this prospectively randomized cadaver study was to investigate whether the
software would facilitate the indirect K-wire placement in the sustentaculum
tali. METHODS: In 20 cadaver foot specimens, K-wires were placed indirectly in
the sustentaculum tali by an experienced and an inexperienced surgeon, with and
without using the application. Number of placement attempts, duration of
procedure, fluoroscopy time, and number of individual fluoroscopy images were
recorded. Each wire's position was analyzed in a 3-dimensional (3D) C-arm scan by
an experienced blinded investigator. RESULTS: Use of the software by the
inexperienced surgeon significantly reduced the number of placement attempts from
3.2 to 1.2 ( P = .006). The application also reduced operating time, from 273 s
to 199 s ( P = .15), and fluoroscopy time, from 41 s to 29 s ( P = .15). Using
the software, the experienced surgeon had a longer operating time (139 s to 183
s; P = .30), longer fluoroscopy time (5.6 s to 9.2 s; P = .17), and more
individual fluoroscopy images (11.6 to 14.8; P = .30). Wire position did not show
significant differences in both cases. CONCLUSION: During indirect K-wire
placement in the sustentaculum tali, the software appeared to be a useful tool
for the inexperienced surgeon. In our chosen study setting, the experienced
surgeon did not benefit from the software. CLINICAL RELEVANCE: Possible
indications for the software would be fractures of the proximal femur, sacrum,
sacroiliac instabilities, vertebral bodies, scaphoid, Lisfranc joint, talus and
calcaneus.
PMID- 29347833
TI - How should we understand family-centred care?
AB - What is family-centred care of a hospitalized child? A critical understanding of
the concept of family-centred care is necessary if this widely preferred model is
to be differentiated from other health care ideals and properly evaluated as
appropriate to the care of hospitalized children. The article identifies
distinguishable interpretations of family-centred care that can pull health
professionals in different, sometimes conflicting directions. Some of these
interpretations are not qualitatively different from robust interpretations of
the ideals of parental participation, care-by-parent and partnership in care that
are said to be the precursors of family-centred care. A prominent interpretation
that regards the child and his or her family collectively as the 'unit of care'
arguably arises from ambiguity and is significantly problematic as a model for
the care of hospitalized children. Clinical practice driven by this
interpretation can include courses of action that do not aim to do what will best
promote a hospitalized child's welfare, and such cases will not be unusual. More
broadly, this interpretation raises challenging questions about the
responsibilities and authority of health professionals in relation to the
interests of hospitalized children and their families.
PMID- 29347834
TI - Acute Care Use for Ambulatory Care-Sensitive Conditions in High-Cost Users of
Medical Care with Mental Illness and Addictions.
AB - OBJECTIVE: The role of mental illness and addiction in acute care use for chronic
medical conditions that are sensitive to ambulatory care management requires
focussed attention. This study examines how mental illness or addiction affects
risk for repeat hospitalization and/or emergency department use for ambulatory
care-sensitive conditions (ACSCs) among high-cost users of medical care. METHOD:
A retrospective, population-based cohort study using data from Ontario, Canada.
Among the top 10% of medical care users ranked by cost, we determined rates of
any and repeat care use (hospitalizations and emergency department [ED] visits)
between April 1, 2011, and March 31, 2012, for 14 consensus established ACSCs and
compared them between those with and without diagnosed mental illness or
addiction during the 2 years prior. Risk ratios were adjusted (aRR) for age, sex,
residence, and income quintile. RESULTS: Among 314,936 high-cost users, 35.9% had
a mental illness or addiction. Compared to those without, individuals with mental
illness or addiction were more likely to have an ED visit or hospitalization for
any ACSC (22.8% vs. 19.6%; aRR, 1.21; 95% confidence interval [CI], 1.20-1.23).
They were also more likely to have repeat ED visits or hospitalizations for the
same ACSC (6.2% vs. 4.4% of those without; aRR, 1.48; 95% CI, 1.44-1.53). These
associations were stronger in stratifications by mental illness diagnostic
subgroup, particularly for those with a major mental illness. CONCLUSIONS: The
presence of mental illness and addiction among high-cost users of medical
services may represent an unmet need for quality ambulatory and primary care.
PMID- 29347835
TI - Senna occidentalis (L.) Link and Senna hirsuta (L.) H. S. Irwin & Barneby:
constituents of fruit essential oils and antimicrobial activity.
AB - Senna occidentalis and S. hirsuta are mostly gathered from the wild for medicinal
use and have a disagreeable odour when crushed. The volatile oils isolated from
fresh fruits of S. occidentalis and S. hirsuta were subjected to gas
chromatography (GC), gas chromatography-mass spectrometry (GC-MS) and
antimicrobial assays. GC and GC-MS analyses permitted the identification of 58
constituents. S. occidentalis oil was dominated by cyperene (10.8%), beta
caryophyllene (10.4%), limonene (8.0%) and caryophyllene oxide (6.8%). The main
components of S. hirsuta fruit oil were benzyl benzoate (24.7%), tau-cadinol
(18.9%), 2,5-dimethoxy-p-cymene (14.6%) and beta-caryophyllene (5.1%). S.
occidentalis fruit oil exhibited better antimicrobial activity (MIC 78-312
MUg/mL) against Escherichia coli, Staphylococcus aureus, Bacillus subtilis and
Aspergillus niger compared with S. hirsuta oil. The compositions and the
activities of the fruit essential oils of S. occidentalis and S. hirsuta are
reported for the first time.
PMID- 29347836
TI - Strategies to overcome resistance mutations of Bruton's tyrosine kinase inhibitor
ibrutinib.
AB - Ibrutinib, as the first Bruton's tyrosine kinase (Btk) inhibitor, has been shown
to have clinically significant activity in leukemias and lymphomas. However, the
initially responsive tumors will develop resistance during the process of
treatment in few patients. Here, we summarized the mechanism of acquired
resistance and suggested the next-generation Btk inhibitors that override the
target resistance. Moreover, the development of combination of selective
antagonists or inhibitors targeting to multiple protein kinases have increased
therapeutic potency to reduce the risk of the emergence of kinases inhibitor
resistance. Thus, the reported combination of therapeutic drugs as an alternative
therapy to overcome ibrutinib collapse or reduce the risk of the emergence of Btk
inhibitor resistance also has been reviewed.
PMID- 29347837
TI - Child Maltreatment and Physical Victimization: Does Heavy Drinking Mediate the
Relationship?
AB - Past studies examining the child maltreatment (CM)/victimization pathway have
been limited by their focus on sexual victimization, narrow windows of
assessment, and failure to examine gender differences. In the current study, we
sought to examine (1) the impact of CM on physical victimization (PV)
trajectories from adolescence to young adulthood and (2) the extent to which
heavy drinking mediated the relationship between CM and later PV. Using three
waves of the National Longitudinal Study of Adolescent to Adult Health, we found
that CM was associated with a 69% greater odds of later PV for both genders,
after the inclusion of control variables, and that the risk continued into
adulthood. Further, heavy drinking was found to mediate the CM/victimization
pathway at Wave I, but not at later waves. When mediation was examined separately
for men and women, support for mediation was found for men and women. The current
study suggests that CM represents a liability for interpersonal violence for both
genders and highlights the importance of looking at victimization across time.
PMID- 29347838
TI - Bacilsubteramide A, a new indole alkaloid, from the deep-sea-derived Bacillus
subterraneus 11593.
AB - From the deep-sea-derived bacterium Bacillus subterraneus 11593, a new indole
alkaloid (1) was isolated along with three known compounds (2-4). By detailed
analysis of its NMR spectroscopic data, and further by the theoretical ECD
calculations, the absolute configuration of the new compound was determined to be
(R)-N-[2-(3-hydroxy-2-oxoindolin-3-yl)ethyl]acetamide, and named bacilsubteramide
A. All four isolates were tested for anti-allergic bioactivities; however, none
exhibited positive effect (IC50 > 0.2 mM). Noteworthily, it is the first report
on secondary metabolites from the bacterium B. subterraneus.
PMID- 29347839
TI - Brain metastases epidemiology in a Tunisian population: trends and outcome.
AB - AIM: We reported anatomo-clinical features of brain metastases (BMs) collected in
a Tunisian medical oncology department. PATIENTS & METHODS: We retrospectively
identified all cases of BM within a cohort of 7055 patients, treated for a
histologically confirmed nonhematological cancer between 2000 and 2016. Data
about age, sex and primary tumor were collected. RESULTS: Incidence was 1.9% and
mean age was 54 years with a 1.24 sex ratio. BMs were symptomatic in 73.7% of
cases after a median time of 16 months. A total of 73.4% patients receiving local
therapy, 88% by whole brain radiation therapy and 21.6% had a metastasectomy.
Lung and breast cancers were the primary in 80% of the BM. CONCLUSION: BM showed
trends of young with underestimated incidence.
PMID- 29347840
TI - Barriers and Enablers to the Implementation of School Wellness Policies: An
Economic Perspective.
AB - BACKGROUND: Local wellness policies (LWPs) are mandated among school systems to
enhance nutrition/physical activity opportunities in schools. Prior research
notes disparities in LWP implementation. This study uses mixed methods to examine
barriers/enablers to LWP implementation, comparing responses by student body
income. METHOD: Schools ( n = 744, 24 systems) completed an LWP implementation
barriers/enablers survey. Semistructured interviews ( n = 20 random subsample)
described barriers/enablers. Responses were compared by majority of lower (>=50%
free/reduced-price meals; lower income [LI]) versus higher income (HI) student
body. RESULTS: In surveys, LI and HI schools identified common barriers
(parents/families, federal/state regulations, students, time, funding) and
enablers (school system, teachers, food service, physical education
curriculum/resources, and staff). Interviews further elucidated how staffing and
funding served as enablers for all schools, and provide context for how and why
barriers differed by income: time, food service (HI schools), and
parents/families (LI schools). CONCLUSIONS: Findings support commonalities in
barriers and enablers among all schools, suggesting that regardless of economic
context, schools would benefit from additional supports, such as physical
education and nutrition education resources integrated into existing curricula,
additional funding, and personnel time dedicated to wellness programming. LI
schools may benefit from additional funding to support parent and community
involvement.
PMID- 29347841
TI - Evolutionary Effect on the Embodied Beauty of Landscape Architectures.
AB - According to the framework of evolutionary aesthetics, a sense of beauty is
related to environmental adaptation and plasticity of human beings, which has
adaptive value and biological foundations. Prior studies have demonstrated that
organisms derive benefits from the landscape. In this study, we investigated
whether the benefits of landscape might elicit a stronger sense of beauty and
what the nature of this sense of beauty is. In two experiments, when viewing
classical landscape and nonlandscape architectures photographs, participants
rated the aesthetic scores (Experiment 1) and had a two-alternative forced choice
aesthetic judgment by pressing the reaction button located near to (15 cm) or far
from (45 cm) the presenting stimuli (Experiment 2). The results showed that
reaction of aesthetic ratings for classical landscape architectures was faster
than those of classical nonlandscape architectures. Furthermore, only the
reaction of beautiful judgment of classical landscape architecture photograph was
significantly faster when the reaction button was in the near position to the
presenting photograph than those in the position of far away from the presenting
photograph. This finding suggests a facilitated effect for the aesthetic
perception of classical landscape architectures due to their corresponding
components including water and green plants with strong evolutionary
implications. Furthermore, this sense of beauty for classical landscape
architectures might be the embodied approach to beauty based on the viewpoint of
evolutionary aesthetics and embodied cognition.
PMID- 29347842
TI - In vitro antioxidant potential and in vivo effects of Schinus terebinthifolia
Raddi leaf extract in diabetic rats and determination of chemical composition by
HPLC-ESI-MS/MS.
AB - The present study investigated the in vitro and in vivo antioxidant potential and
phytochemical composition of Schinus terebinthifolia, which is widely used in
folk medicine for various therapeutic purposes. The in vitro analyses indicated
that the hydroethanolic extract (HE) had 312.50 +/- 0.50 mg GAE/g of total
phenols. It also presented anti-DPPH* and anti-ABTS*+ activity, reduced
phosphomolybden and metal ions and blocked the bleaching of beta-carotene. The HE
at concentrations of 3.0 and 2.0 MUg/mL had TRAP values of 2.223 +/- 0.018 and
1.894 +/- 0.026 MUM Trolox, respectively. The HE increased the availability of
antioxidants in plasma in treated animals in vivo. HPLC-ESI-MS/MS indicated the
presence of 11 phenols: cumaric acid, (+)-catechin, myricetin-3-O-glicuronide,
kaempferol-3-O-glucoside, myricetin, myricitrin, quercetin, gallic acid, methyl
galate, pentagalloyl glucose and ethyl galate. Thus, S. terebinthifolia has
potential for the prevention or treatment of diseases that are related to
oxidative stress, such as diabetes mellitus.
PMID- 29347843
TI - Combinatorial design and virtual screening of potent anti-tubercular
fluoroquinolone and isothiazoloquinolone compounds utilizing QSAR and
pharmacophore modelling.
AB - The virulence of tuberculosis infections resistant to conventional combination
drug regimens cries for the design of potent fluoroquinolone compounds to be used
as second line antimycobacterial chemotherapeutics. One of the most effective in
silico methods is combinatorial design and high throughput screening by a ligand
based pharmacophore prior to experiment. The combinatorial design of a series of
3850 fluoroquinolone and isothiazoloquinolone compounds was then screened
virtually by applying a topological descriptor based quantitative structure
activity relationship (QSAR) for predicting highly active congeneric quinolone
leads against Mycobacterium fortuitum and Mycobacterium smegmatis. The predicted
highly active congeneric hits were then subjected to a comparative study between
existing lead sparfloxacin with fluoroquinolone FQ hits as well as ACH-702 with
predicted active isothiazoloquinolones, utilizing pharmacophore modelling to
focus on the mechanism of drug binding against mycobacterial DNA gyrase. Finally,
68 compounds including 34 FQ and 34 isothiazoloquinolones were screened through
high throughput screening comprising QSAR, the Lipinski rule of five and ligand
based pharmacophore modelling.
PMID- 29347844
TI - Docking analysis targeted to the whole enzyme: an application to the prediction
of inhibition of PTP1B by thiomorpholine and thiazolyl derivatives.
AB - PTP1b is a protein tyrosine phosphatase involved in the inactivation of insulin
receptor. Since inhibition of PTP1b may prolong the action of the receptor, PTP1b
has become a drug target for the treatment of type II diabetes. In the present
study, prediction of inhibition using docking analysis targeted specifically to
the active or allosteric site was performed on 87 compounds structurally
belonging to 10 different groups. Two groups, consisting of 15 thiomorpholine and
10 thiazolyl derivatives exhibiting the best prediction results, were selected
for in vitro evaluation. All thiomorpholines showed inhibitory action (with IC50
= 4-45 MUMU, Ki = 2-23 MUM), while only three thiazolyl derivatives showed low
inhibition (best IC50 = 18 MUMU, Ki = 9 MUMU). However, free binding energy (E)
was in accordance with the IC50 values only for some compounds. Docking analysis
targeted to the whole enzyme revealed that the compounds exhibiting IC50 values
higher than expected could bind to other peripheral sites with lower free energy,
Eo, than when bound to the active/allosteric site. A prediction factor, E-
(SigmaEo * 0.16), which takes into account lower energy binding to peripheral
sites, was proposed and was found to correlate well with the IC50 values
following an asymmetrical sigmoidal equation with r2 = 0.9692.
PMID- 29347845
TI - Introductory paragraph.
PMID- 29347847
TI - Combining cell and gene therapy to advance cardiac regeneration.
AB - INTRODUCTION: The characterization of multipotent endogenous cardiac stem cells
(eCSCs) and the breakthroughs of somatic cell reprogramming to boost
cardiomyocyte replacement have fostered the prospect of achieving functional
heart repair/regeneration. Areas covered: Allogeneic CSC therapy through its
paracrine stimulation of the endogenous resident reparative/regenerative process
produces functional meaningful myocardial regeneration in pre-clinical porcine
myocardial infarction models and is currently tested in the first-in-man human
trial. The in vivo test of somatic reprogramming and cardioregenerative non
coding RNAs revived the interest in gene therapy for myocardial regeneration. The
latter, together with the advent of genome editing, has prompted most recent
efforts to produce genetically-modified allogeneic CSCs that secrete
cardioregenerative factors to optimize effective myocardial repair. Expert
opinion: The current war against heart failure epidemics in western countries
seeks to find effective treatments to set back the failing hearts prolonging
human lifespan. Off-the-shelf allogeneic-genetically-modified CSCs producing
regenerative agents are a novel and evolving therapy set to be affordable, safe,
effective and available at all times for myocardial regeneration to either
prevent or treat heart failure.
PMID- 29347846
TI - Poly (butylene adipate-co-butylene terephthalate) nanoparticles prepared by
electrospraying technique for docetaxel delivery in ovarian cancer induced mice.
AB - OBJECTIVE: Ovarian cancer is still a major cause of morbidity and mortality.
Docetaxel (DTX) is one of the most notable cytotoxic agents for treatment of
ovarian cancer. However, its side effects proposed considerable problems to the
patients. SIGNIFICANCE: Polymeric nanoparticles (NPs) of poly (butylene adipate
co-butylene terephthalate) (Ecoflex(r)), a biodegradable and biocompatible
polymer, were prepared for the first time by the upgradeable electrospraying
technique. METHODS: The formulation and procedure variables were optimized using
Design Expert software, and effect of each variable on particle size, particle
size distribution, drug entrapment efficiency, and drug release of the NPs were
evaluated. Then, in vitro cytotoxicity, cellular uptake, X-ray diffraction
pattern, and morphological characteristics of the optimized NPs were evaluated.
Finally, in vivo efficacy of the DTX-loaded NPs was evaluated on tumor bearing
nude mice. RESULTS: The optimum condition for production of NPs included voltage
of 20 kV, 12 cm distance between electrodes, feeding rate of 1 mL/hr, polymer to
drug ratio of 3:1, 1 w/v% of Pluronic-F127 and dichloromethane to dimethyl
formamide ratio of 2.7:1. Fluorescent microscopy test showed the NPs were
successfully up-taken by ovarian cancer cells. In vitro cytotoxicity test
confirmed no cytotoxic effect caused by blank NPs, while cell viability of the
DTX loaded NPs was significantly lower than the free DTX (p < .05). The NPs
significantly enhanced anti-tumor efficacy of the drug in nude mice (p < .05).
CONCLUSION: The Ecoflex(r) NPs could potentially provide a suitable alternative
for currently available formulations of DTX.
PMID- 29347848
TI - Role of topical oxytocin in improving vaginal atrophy in postmenopausal women: a
randomized, controlled trial.
AB - OBJECTIVE AND DESIGN: Prospective randomized controlled trial to test the
effectiveness of topical oxytocin gel to improve vaginal atrophy in
postmenopausal women. PATIENTS AND METHODS: A total of 140 postmenopausal women
presenting with vaginal atrophy and who satisfied the inclusion and exclusion
criteria were randomized into two groups each of 70 patients; they received
intravaginal oxytocin gel or placebo gel for 30 days. Serum estrogen level,
visual, colposcopic and histological vaginal examination were performed before
and after treatment. RESULTS: Forty-seven out of 70 women in the oxytocin gel
group improved after treatment and none in the placebo group (p = 0.001). Forty
five participants in the oxytocin group and seven in the placebo group reported
relief of dyspareunia (p = 0.001). Thirty-four participants in the oxytocin group
and seven in the placebo group reported relief of soreness (p = 0.001). There was
no significant difference between the circulating levels of estradiol in both
groups before and after treatment (p = 0.4 and 0.6 for the oxytocin group and the
placebo group, respectively). CONCLUSION: Oxytocin gel is useful in the
restoration of the vaginal epithelium in cases of postmenopausal atrophic
vaginitis. Further studies with a longer follow-up period are required to test
the long-term effects of oxytocin as a treatment for vaginal atrophy.
PMID- 29347849
TI - Joint pain within adult middle-aged women, attending a community clinic in a peri
urban area in South Africa: a cross-sectional survey.
AB - BACKGROUND: This study aimed to investigate the prevalence of joint pain in women
between the ages of 40 and 64 years who attended a community clinic in the Free
State to provide micro-information for health care planners. METHODS: A sample of
convenience was utilized in the cross-sectional survey. Health care workers were
recruited to conduct the survey. Outcome measures included the Community-Oriented
Programme-For-The-Control-Of-Rheumatic-Disease questionnaire and European Quality
of Life - 5 Dimensions health related quality of life measure. Descriptive
statistics were calculated for categorical data and non-parametric tests for
ordinal data. Quality Adjusted Life Years lost were based on the preference
weights generated by the European Quality of Life - 5 Dimensions. RESULTS: One
thousand three hundred seventy-six participants were enrolled. The prevalence of
joint pain experienced in either the short or the long term was 62.1% (CI 59.5
64.6%). The total number of Quality Adjusted Life Years lost in this sample was
41.4, that is a rate of 3008.7 (CI 2740-3310) per 100,000. CONCLUSION:
Epidemiological transition seems to be rapidly taking place in South Africa and
the prevalence of joint pain is considerable. Primary health care systems should
develop a cost-effective approach to manage and identify joint pain and improve
the health-related quality of life of those living with this. Implications for
Rehabilitation Prevalence of joint pain is considerable. Consume large amounts of
health and social resources. A protocol for routine screening should be developed
in community clinics. Cost-effective approach to manage joint pain should be
identified to improve healthrelated quality of life of individuals living with
joint pain.
PMID- 29347850
TI - Feasibility of electrospray deposition for rapid screening of the cocrystal
formation and single step, continuous production of pharmaceutical
nanococrystals.
AB - OBJECTIVES: This study employed electrospray deposition (ESD) for simultaneous
synthesis and particle engineering of cocrystals. SIGNIFICANCE: Exploring new
methods for the efficient production of cocrystals with desired particle
properties is an essential demand. METHODS: The possibility of cocrystal
formation by ESD was examined for indomethacin-saccharin, indomethacin
nicotinamide, naproxen-nicotinamide, and naproxen-iso-nicotinamide cocrystals.
Solutions of the drug and coformer at stoichiometric ratios were sprayed to a
high electric field which caused rapid evaporation of the solvent and the
formation of fine particles. The phase purity, size, and morphology of products
were compared with reference cocrystals. Experiments were performed to evaluate
the effects of stoichiometric ratio, concentration and solvent type on the
cocrystal formation. Physical stability and dissolution properties of the
electrosprayed cocrystals were also compared with reference cocrystals. RESULTS:
ESD was found to be an efficient and rapid method to produce cocrystals for all
studied systems other than indomethacin-nicotinamide. Pure cocrystals only formed
at a specific drug:coformer ratio. The solvent type has a weak effect on the
cocrystal formation and morphology. Electrosprayed cocrystals exhibited nano to
micrometer sizes with distinct morphologies with comparable physical stability
with reference cocrystals. Nanococrystals of indomethacin-saccharin with a mean
size of 219 nm displayed a threefold higher dissolution rate than solvent
evaporated cocrystal. CONCLUSION: ESD successfully was utilized to produce pure
cocrystals of poorly soluble drugs with different morphologies and sizes ranging
from nano to micrometer sizes in one step. This study highlighted the usefulness
of ESD for simultaneous preparation and particle engineering of pharmaceutical
cocrystals.
PMID- 29347851
TI - The era of biofunctional biomaterials in orthopedics: what does the future hold?
AB - INTRODUCTION: Titanium-based materials do not fulfill all of the requirements of
orthopedic implants due to a mismatch in mechanical properties with bone which
are prone to change during the course of bone growth. Biofunctional biomaterials
are a new class of materials that show bioactivity and adaptability at any stage
of bone growth. Areas covered: Different biofunctional biomaterials have evolved
over time that can enhance calcium phosphate (CaP) precipitation, stimulate
osteogenic differentiation, and can control osteoblast gene expression. These
materials include metals or metal alloys, ceramics, polymers and biocomposites.
Similarly, naturally-inspired nanomaterials and nanometer surface featured
modified materials can enhance bone growth if created to match bone's unique
micro to nano hierarchical structure. Nanoscale manipulation of existing
biomaterials can incorporate antimicrobial properties which is desirable to
prevent infection and failure of orthopedic devices. Expert commentary: Recent
research trends in biofunctional biomaterials have focused to, first, understand
the bone growth mechanism and, then, mimic natural bone architecture using
biomaterials. Therefore, an enhanced understanding of material properties and
tissue engineering principles will lead the way forward designing biofunctional
biomaterials. In the future, the role of biofunctional biomaterials and
orthopedic sensors will be more pronounced in terms of musculoskeletal disease
prevention, diagnosis, and treatment.
PMID- 29347852
TI - The patient categorisation tool: psychometric evaluation of a tool to measure
complexity of needs for rehabilitation in a large multicentre dataset from the
United Kingdom.
AB - PURPOSE: This first psychometric evaluation of the Patient Categorisation Tool
examined its properties as an instrument to measure complexity of needs in a
mixed population of patients presenting for specialist neurorehabilitation.
MATERIALS/METHODS: Analysis of a large multicentre cohort of patients (n = 5396)
from the national clinical dataset representing 63 specialist rehabilitation
services across England. Structural validity was examined using exploratory and
confirmatory factor analysis. Concurrent and criterion-validity were tested
through a priori hypothesized relationships with other validated measures of
resource requirements and dependency. RESULTS: All but two items loaded strongly
onto a single principal component with Cronbach's alpha 0.88. A total score of
>=30 identified patients with complex (category A) needs with sensitivity 76% and
specificity 75%. However, confirmatory factor analysis provided a better fit when
the scale was split into two subscales - a 'Cognitive/psychosocial' and a
'Physical' sub-scale (alpha 0.83 and 0.84, respectively). Moderate convergent and
discriminant correlations were consistent with hypothesized relationships.
CONCLUSIONS: The findings provide some overall support for the Patient
Categorisation Tool as a unidimensional tool for measuring complexity of needs
for neurorehabilitation, but the subscales may be more suitable for certain
groups of patients. Further analysis is now required to evaluate its performance
in different conditions. Implications for Rehabilitation A psychometrically
robust tool for measuring the complexity of rehabilitation needs has potential
value, both at an individual level for treatment planning, and at a population
level for planning and commissioning rehabilitation services. The Patient
Categorisation Tool now forms part of the United Kingdom national clinical
dataset mandated by the National Health Service in England This psychometric
analysis from a large national multicentre cohort representing a diverse range of
conditions, provides evidence for its validity as a means to identity patients
with complex rehabilitation needs requiring specialist rehabilitation.
PMID- 29347853
TI - SAR thresholds for electromagnetic exposure using functional thermal dose limits.
AB - BACKGROUND AND PURPOSE: To protect against any potential adverse effects to human
health from localised exposure to radio frequency (100 kHz-3 GHz) electromagnetic
fields (RF EMF), international health organisations have defined basic
restrictions on specific absorption rate (SAR) in tissues. These exposure
restrictions incorporate safety factors which are generally conservative so that
exposures that exceed the basic restrictions are not necessarily harmful. The
magnitude of safety margin for various exposure scenarios is unknown. This
shortcoming becomes more critical for medical applications where the safety
guidelines are required to be relaxed. The purpose of this study was to quantify
the magnitude of the safety factor included in the current basic restrictions for
various exposure scenarios under localised exposure to RF EMF. MATERIALS AND
METHODS: For each exposure scenario, we used the lowest thermal dose (TD)
required to induce acute local tissue damage reported in literature, calculated
the corresponding TD-functional SAR limits (SARTDFL) and related these limits to
the existing basic restrictions, thereby estimating the respective safety factor.
RESULTS: The margin of safety factor in the current basic restrictions on 10 g
peak spatial average SAR (psSAR10g) for muscle is large and can reach up to 31.2.
CONCLUSIONS: Our analysis provides clear instructions for calculation of SARTDFL
and consequently quantification of the incorporated safety factor in the current
basic restrictions. This research can form the basis for further discussion on
establishing the guidelines dedicated to a specific exposure scenario, i.e.
exposure-specific SAR limits, rather than the current generic guidelines.
PMID- 29347854
TI - A systematic review of health economic models and utility estimation methods in
schizophrenia.
AB - INTRODUCTION: There is a growing need for economic evaluations describing the
disease course, as well as the costs and clinical outcomes related to the
treatment of schizophrenia. Areas covered: A systematic review on studies
describing health economic models in schizophrenia and a targeted literature
review on utility mapping algorithms in schizophrenia were carried out. Models
found in the review were collated and assessed in detail according to their type
and various other attributes. Fifty-nine studies were included in the review.
Modeling techniques varied from simple decision trees to complex simulation
models. The models used various clinical endpoints as value drivers, 47% of the
models used quality-adjusted life years, and eight percent used disability
adjusted life years to measure benefits, while others applied various clinical
outcomes. Most models considered patients switching between therapies, and
therapeutic adherence, compliance or persistence. The targeted literature review
identified four main approaches to map PANSS scores to utility values. Expert
commentary: Health economic models developed for schizophrenia showed great
variability, with simulation models becoming more frequently used in the last
decade. Using PANSS scores as the basis of utility estimations is justifiable.
PMID- 29347855
TI - Low-power bipolar radiofrequency ablation and vertebral augmentation for the
palliative treatment of spinal malignancies.
AB - AIM: To investigate the analgesic properties and the safety of low power bipolar
radiofrequency ablation (RFA) performed with internally cooled electrodes and
vertebral augmentation for the treatment of painful spinal malignancies.
MATERIALS AND METHODS: Consent was waived for retrospective study participation.
Review of electronic records identified 11 consecutive patients (6 females; 5
males; mean age 61.3 +/- 11.6 years) with one-index painful spinal tumour, who
were treated between June 2016 and October 2017 with bipolar RFA and vertebral
augmentation. Patients were treated if they presented with focal pain (>=4/10 on
a 0-10 visual analogic scale in the 24-h period) corresponding to a metastatic
vertebral level on cross sectional imaging. The Wilcoxon test was used to
evaluate the significance of the post-operative pain. RESULTS: Lumbar levels were
treated in 72.7% cases; metastatic epidural involvement was noted in 81.8% cases;
54.5% patients received associated treatments in addition to RFA, which was
coupled to vertebral augmentation in all cases. Two (18.2%) complications were
noted. Mean pain score measured at last clinical follow-up available (mean 1.9 +/
1.4 months) was 3.5 +/- 2 (versus 7.8 +/- 1.1 at baseline; p <0.01).
CONCLUSIONS: Low-power bipolar RFA performed with internally cooled electrodes
and coupled to vertebral augmentation provides safe and effective early analgesia
in patients affected by painful spinal malignancies.
PMID- 29347856
TI - Systematic review of injuries in mixed martial arts.
AB - OBJECTIVES: To assess injury rates in all mixed martial arts (MMA) studies.
METHODS: Six online databases were searched until November 2017 including
MEDLINE, EMBASE, CINAHL, Web of Science, PubMed, Google/Google Scholar and
conference proceedings. All included studies were entered in Pub Med Single
Citation Matcher and all citation chains followed. Abstracts and titles were
assessed for relevance, data independently abstracted and risk of bias for all
competition studies evaluated independently by two reviewers. RESULTS: There are
data for 5,374 male and 108 female MMA fighters. For 2407 males the weighted
average injury rate/1000Athletic Encounters (AE) was 246.4 and for one study of
108 females 101.9. One study provided data by professional status: professionals
135.5/1000AE and amateurs 71.0/1000AE. Reasons for stopping matches were
knockout/technical knockout 173.9/1000AE for males and 175.9/1000AE for females,
submission 228.6/1000AE, and referee's decision 98.2/1000AE. Losers can
experience large amounts of trauma especially head trauma as matches terminate.
Two studies of competitions provided personally conducted ringside assessments
and both pre- and post-match examination results. The other studies reported
retrospective assessments of fight records or videos or videos and scorecards.
There are no studies of training injuries of professionals or injuries of
amateurs or long-term follow-up of musculoskeletal injuries or neurological
damage. Studies are limited to the US and Canada. There are no systematic reviews
of newspaper or media accounts of fights to assess rates and numbers of injuries
or mortality. The few published surveys and case reports markedly understate the
worldwide situation. CONCLUSIONS: There are high rates of trauma in MMA. The
authorities who regulate MMA and referees and physicians who monitor MMA fighters
have an inadequate database to guide their work. Researchers need to adopt the
same set of complete definitions of all possible injuries and measure the high
and early rate of neurological damage.
PMID- 29347857
TI - Mulberry leaves and their potential effects against cardiometabolic risks: a
review of chemical compositions, biological properties and clinical efficacy.
AB - CONTEXT: Cardiometabolic risks are regarded as the crucial factors associated
with type 2 diabetes (T2DM) and cardiovascular diseases (CVD). Regarding an
increased attention to medicinal plants in the current healthcare system, the
effects of mulberry (Morus spp., Moraceae) leaves on cardiometabolic risks have
been consecutively considered in scientific research. OBJECTIVE: The present
review compiles and summarizes the chemical compositions, biological properties
and clinical efficacy of mulberry leaves that are related to the amelioration of
cardiometabolic risks. METHODS: Published English literature from the PubMed,
Science Direct and Google Scholar databases was searched by using 'mulberry
leaves' 'Morus spp.', 'hyperglycemia', 'hyperlipidemia', 'obesity',
'hypertension', 'oxidative stress', 'atherosclerosis' and 'cardiovascular
diseases' as the keywords. The relevant articles published over the past two
decades were identified and reviewed. RESULTS: Mulberry leaves contain numerous
chemical constituents. 1-Deoxynojirimycin (DNJ), phenolics and flavonoids are the
prominent functional compounds. Preclinical and clinical studies showed that
mulberry leaves possessed various beneficial effects against cardiometabolic
risks, including antihyperglycaemic, antihyperlipidaemic, antiobesity,
antihypertensive, antioxidative, anti-inflammatory, anti-atherosclerotic and
cardioprotective effects. CONCLUSIONS: Mulberry leaves could be a promising
therapeutic option for modulating cardiometabolic risks. However, further
investigations should be performed to substantiate the potential of mulberry
leaves in practical uses.
PMID- 29347858
TI - Where are we with injectables against HIV infection and what are the remaining
challenges?
AB - INTRODUCTION: Drug adherence has been a recurring issue in the field of HIV
treatment, and low treatment adherence is typically associated with emergence of
drug resistance, treatment failure and increased risks of transmission.
Injectable antiretroviral drugs offer a unique opportunity to counter this issue
for the treatment of HIV-positive individuals. In addition, injectables offer a
remarkable opportunity to reduce new HIV infections, if applied in the context of
both treatment-as-prevention and pre-exposure prophylaxis. Areas covered:
Researchers and drug companies are developing long-acting agents that possess
long biological half-life and excellent pharmacokinetic profiles that can be
administered intramuscularly, intravenously, or subcutaneously. These long-acting
injectables are categorized as drugs that target different steps of HIV
replication cycle or monoclonal antibodies that target HIV entry. Expert
commentary: Injectables against HIV have the potential to revolutionize the fight
against HIV by facilitating both treatment and prevention in a wide variety of
clinical settings. Several challenges remain including the identification of
potent two-drug combinations of drugs that can be formulated as injectables, and
thorough drug-drug interaction studies with a broad variety of medications.
Finally we believe that the healthcare benefits of injectables will require
regulatory changes to allow self-injection before they reach their full
potential.
PMID- 29347859
TI - PACTRIMS 2017.
PMID- 29347860
TI - Alteration of auditory function in type 2 diabetic and pre-diabetic patients.
AB - BACKGROUND: The association between type 2 diabetes mellitus (T2DM) and hearing
loss has not been fully investigated and there is little information on the
effects of pre-diabetes on alterations in auditory function in Chinese subjects.
METHODS: The study recruited 51 patients with T2DM, 55 patients with pre-diabetes
and 43 control subjects. Auditory function was assessed by pure tone audiometry
(PTA) tests and distortion product of otoacoustic emissions (DPOAEs). Tinnitus
symptoms were recorded using a medical history questionnaire. RESULTS: A
significantly larger number of patients with T2DM (45.1%) were affected by
hearing loss, compared to pre-diabetes patients (23.6%; p = .04) and control
subjects (25.6%; p = .02), as assessed by PTA. There was no significant
difference in PTA between the number of pre-diabetes patients and control
subjects. In contrast, mean DPOAEs amplitudes of the pre-diabetes patients were
significantly lower than of the control subjects, at all frequencies
investigated, except 0.75 kHz. A significantly greater number of pre-diabetes
patients reported tinnitus symptoms. CONCLUSIONS: Diabetes is associated with
bilateral sensorineural hearing loss, especially at high frequencies. While pre
diabetes is not necessarily associated with significant hearing loss, there may
be cochlear malfunction, as indicated by DPOAEs. Thus, patients with pre-diabetes
who have tinnitus may benefit from DPOAEs and PTA tests.
PMID- 29347861
TI - Positive emotional attention bias in young children with symptoms of ADHD.
AB - Children with attention-deficit/hyperactivity disorder (ADHD) often experience
emotional dysregulation. Dysregulation can arise from heightened attention to
emotional stimuli. Emotional attention biases are associated with a number of
adverse socioemotional outcomes including reward sensitivity and externalizing
behaviors. As reward sensitivity and externalizing behaviors are common in
children with ADHD, the aim of the current study was to determine whether
emotional attention biases are evident in young children with clinically
significant ADHD symptoms. To test this, children with (n = 18) and without (n =
15) symptoms of ADHD were tested on a Dot Probe task. Provided recent evidence
that emotional attention biases are attenuated by sleep, the task was performed
before and after overnight sleep. Children with ADHD symptoms displayed positive,
but not negative, attention biases at both time points, whereas typically
developing children did not preferentially attend toward or away from positive or
negative stimuli. Sleep did not alter attention biases in either group.
Collectively, these results indicate that children with ADHD symptoms have
stable, positive attention biases.
PMID- 29347862
TI - Survey of the awareness of adult rheumatologists regarding transitional care for
patients with juvenile idiopathic arthritis in Japan.
AB - OBJECTIVES: To understand the current status of adult rheumatology care for
patients who had previously had juvenile idiopathic arthritis (JIA) (excluding
systemic JIA), and to identify issues interfering with the transition from
pediatric to adult care in Japan. METHODS: Questionnaire-based survey among 30
adult rheumatologists. RESULTS: Eighty-seven percent of adult rheumatologists
responded that they had provided medical care to adults who had had JIA; 44% of
them had felt hesitation or anxiety when providing such care. The reasons for
this included lack of independence of the patients, lack of knowledge and
experience among adult rheumatologists, and lack of preparation for accepting
such patients. Many adult rheumatologists believed that the timing of transition
from pediatric to adult rheumatology care must be considered based on therapeutic
regimens or clinical conditions/disease states, not solely chronological age. A
majority of adult rheumatologists showed great interest in transitional care for
JIA patients and desired to communicate better with pediatric rheumatologists.
CONCLUSION: Transitional care for JIA patients is not sufficiently developed in
Japan. Education and advocate campaign of transitional care is required for adult
rheumatologists as well as patients and their parents.
PMID- 29347864
TI - Dense Breast Notification Laws: Impact on Downstream Imaging After Screening
Mammography.
AB - Dense breast tissue is a common finding that decreases the sensitivity of
mammography in detecting cancer. Many states have recently enacted dense breast
notification (DBN) laws to provide patients with information to help them make
better-informed decisions about their health. To test whether DBN legislation
affected the probability of screening mammography follow-up by ultrasound and
magnetic resonance imaging (MRI), we examined the proportion of times screening
mammography was followed by ultrasound or MRI for a series of months pre- and
post-legislation. The subjects were women aged 40 to 64 years, covered by private
health insurance, undergoing screening mammography from 2007 to 2014. Except for
Hawaii, Maryland, and New York, DBN legislation significantly increased the
probability of ultrasound follow-up in all states that implemented DBN
legislation before December 2014. It also increased the probability of MRI follow
up in California, North Carolina, Pennsylvania, and Texas. The financial and
access consequences merit further study.
PMID- 29347863
TI - An Intervention to Improve Physical Function and Caregiver Perceptions in Family
Caregivers of Persons With Heart Failure.
AB - OBJECTIVE: This randomized controlled trial was conducted to determine whether a
12-week home-based aerobic and resistance exercise program would improve physical
function and caregiving perceptions among family caregivers (FCGs) of persons
with heart failure. METHOD: Overall, 127 FCGs were randomized to one of three
groups: usual care attention control (UCAC), psychoeducation only (PE), and
psychoeducation plus exercise (PE + EX). Physical function measures (6-min walk
test, handgrip, and upper and lower strength) and caregiving perceptions (Bakas
Caregiving Outcomes Scale) were obtained at baseline and at 6 months. RESULTS:
FCGs in the PE + EX showed significant improvement in 6-min walk distance ( p =
.012), handgrip, and lower extremity strength compared with the PE and UCAC
groups. The combined group had the greatest improvement in caregiver perceptions
( p < .001). CONCLUSION: FCGs in the PE + EX group improved the most in physical
function and caregiver perception outcomes. Directions for future research are
provided.
PMID- 29347865
TI - The Influence of Multimorbidity on Leading Causes of Death in Older Adults With
Cognitive Impairment.
AB - OBJECTIVE: The aim of this study is to evaluate the relationship of leading
causes of death with gradients of cognitive impairment and multimorbidity.
METHOD: This is a population-based study using data from the linked 1992-2010
Health and Retirement Study and National Death Index ( n = 9,691). Multimorbidity
is defined as a combination of chronic conditions, functional limitations, and
geriatric syndromes. Regression trees and Random Forest identified which
combinations of multimorbidity associated with causes of death. RESULTS:
Multimorbidity is common in the study population. Heart disease is the leading
cause in all groups, but with a larger percentage of deaths in the mild and
moderate/severe cognitively impaired groups than among the noncognitively
impaired. The different "paths" down the regression trees show that the
distribution of causes of death changes with different combinations of
multimorbidity. DISCUSSION: Understanding the considerable heterogeneity in
chronic conditions, functional limitations, geriatric syndromes, and causes of
death among people with cognitive impairment can target care management and
resource allocation.
PMID- 29347866
TI - Effects of cereal bar containing polydextrose on subjective feelings of appetite
and energy intake in overweight adults over 15 d.
AB - The effects of 15 d polydextrose (16.7 g) consumption on energy intake (EI) and
appetite feelings were investigated. Overweight adults consumed a polydextrose
bar or a control-bar matched in energy content as a midmorning snack for 15
consecutive days in a single-blind, randomised, crossover design. The two 15-d
intervention periods were separated by a 15-d washout period. On the day 1 and
the day 15 of each intervention period, energy intake (primary outcome) and
appetite feelings (secondary outcome) were assessed. There were not significant
main effects of the day, type of bar, or their interaction for EI (at lunchtime
test meal, at rest of the day, or at total daily) or subjective feelings (hunger,
desire to eat, fullness, and prospective food consumption) during the satiation
and satiety periods. The results showed the consumption of polydextrose-bar
during 15 d did not significantly affect energy intake and subjective feelings of
appetite in overweight adults.
PMID- 29347867
TI - The Mediterranean Diet: its definition and evaluation of a priori dietary indexes
in primary cardiovascular prevention.
AB - We have analysed the definition of Mediterranean Diet in 28 studies included in
six meta-analyses evaluating the relation between the Mediterranean Diet and
primary prevention of cardiovascular disease. Some typical food of this dietary
pattern like whole cereals, olive oil and red wine were taken into account only
in a few a priori indexes, and the dietary pattern defined as Mediterranean
showed many differences among the studies and compared to traditional
Mediterranean Diet of the early 1960s. Altogether, the analysed studies show a
protective effect of the Mediterranean Diet against cardiovascular disease but
present different effects against specific conditions as cerebrovascular disease
and coronary heart disease. These different effects might depend on the
definition of Mediterranean Diet and the indexes of the adhesion to the same one
used. To compare the effects of the Mediterranean Diet against cardiovascular
disease, coronary heart disease and stroke a univocal model of Mediterranean Diet
should be established as a reference, and it might be represented by the Modern
Mediterranean Diet Pyramid. The a priori index to evaluate the adhesion to
Mediterranean Diet might be the Mediterranean-Style Dietary Pattern Score that
has some advantages in comparison to the others a priori indexes.
PMID- 29347868
TI - Differential White Matter Regional Alterations in Motor Subtypes of Early Drug
Naive Parkinson's Disease Patients.
AB - BACKGROUND: Parkinson's disease (PD) can be classified into tremor dominant (TD)
and postural instability and gait difficulty (PIGD) subtypes with TD considered
as the benign subtype. The neural alterations of the 2 subtypes in the early
stages before administration of medications remain elusive. OBJECTIVE: This study
assessed the subtype-related white matter (WM) microstructural features in newly
diagnosed and drug-naive PD patients from the Parkinson's Progression Markers
Initiative (PPMI). METHODS: Sixty-five early PDs with stable subtypes (52 TD and
13 PIGD patients) and 61 controls underwent diffusion tensor imaging (DTI)
scanning and clinical assessment. Tract-based special statistics (TBSS), graph
theoretical and network-based analyses were used to compare WM regional and
network features between groups. RESULTS: No differences in disease stages and
duration were found between the 2 patient groups. TD patients showed increased
fractional anisotropy (FA), but decreased radial and axial diffusivities (RD and
AD) in several projection, association, and commissural tracts, compared with
PIGD patients and controls. Motor severity had mild-to-moderate correlations with
FA and RD of the corpus callosum (genu) in TD, but strong correlations with FA
and RD of multiple association tracts in PIGD. Conversely, no significant network
changes were noted. CONCLUSIONS: TD patients showed regionally increased FA but
decreased diffusivities, implying neural reorganization to compensate PD
pathology in early stages. PIGD patients, despite having similar disease stages
and duration, exhibited more WM degradation. These results demonstrate
differential WM regional features between the 2 subtypes in early PD and support
the notion of TD being a benign subtype.
PMID- 29347869
TI - Social Support Networks and Quality of Life of Rural Men in a Context of Marriage
Squeeze in China.
AB - A significant number of rural Chinese men are facing difficulties in finding a
spouse and may fail to ever marry due to a relative scarcity of women in the
adult population. Research has indicated that marriage squeeze is a stressful
event which is harmful to men's quality of life, and also weakens their social
support networks. Using data collected in rural Chaohu city, Anhui, China, this
study explores the effects of social support networks on quality of life of rural
men who experience a marriage squeeze. The results indicate that the size of
social contact networks is directly and positively associated with the quality of
life of marriage-squeezed men, and moderate the negative effect of age on quality
of life. Having no or limited instrumental support network and social contact
network are double-edged swords, which have direct negative associations with the
quality of life of marriage-squeezed men, and have moderate effects on the
relationship between marriage squeeze and quality of life.
PMID- 29347870
TI - Incorporating living from the heart into medical education.
AB - Medical training poses many challenges to trainees' wellbeing. To address the
impact of learning in a high turnover, high volume, acute care setting in the
General Internal Medicine Clinical Teaching Unit, the Chief Medical Resident, in
this personal account, shares how she and the Spiritual Care Practitioner united
to form an innovative partnership. The introduction of the skills of spiritual
care practitioners, generally referred to patients and families, to support
medical students and residents resulted in the co-development and co
implementation of a unique, reflective, one-hour session. The objective was to
create a protected space and time to discuss the impact of training and clinical
experiences on medical trainees' wellbeing, in the context of "living from the
heart".
PMID- 29347871
TI - Commentary on "Regulatory Support Improves Subsequent IRB/REC Approval Rates in
Studies Initially Deemed Not Ready for Review: A CTSA Institution's Experience".
AB - In response to researcher concerns a number of initiatives have been developed to
support individual researchers seeking ethics review and approval. In this issue,
Sonne et al. (2017) outline an example of an intervention to support researchers,
which they refer to as a Regulatory Knowledge Support (RKS) service. While the
study points to potential benefits, other studies have not had the desired impact
on key performance measures. There is a need to develop a community of practice
and expand the burgeoning evidence base regarding what interventions work, for
whom, and under what circumstances. Advancing the research agenda requires: the
development of theoretical models for intervention design and evaluation;
developing consensus on key data for collection and measures of effectiveness;
conducting evaluations using the strongest possible study designs, and;
publishing the findings of evaluations.
PMID- 29347873
TI - Students with an autonomous role in hospital care - patients perceptions.
AB - BACKGROUND: There have been calls to enhance clinical education by strengthening
supported active participation (SAP) of medical students in patient care. This
study examines perceived quality of care when final-year medical students are
integrated in hospital ward teams with an autonomous relationship toward their
patients. METHODS: We established three clinical education wards (CEWs) where
final-year medical students were acting as "physician under supervision". A
questionnaire-based mixed-method study of discharged patients was completed in
2009-15 using the Picker Inpatient Questionnaire complemented by specific
questions on the impact of SAP. Results were compared with matched pairs of the
same clinical specialty from the same hospital (CG1) and from nationwide
hospitals (CG2). Patients free-text feedback about their hospital stay was
qualitatively evaluated. RESULTS: Of 1136 patients surveyed, 528 (46.2%) returned
the questionnaire. The CEWs were highly recommended, with good overall quality of
care and patient-physician/student-interaction, all being significantly (p <
0.001) higher for the CEW group while experienced medical treatment success was
similar. Patient-centeredness of students was appreciated by patients as a
support to a deeper understanding of their condition and treatment. CONCLUSION:
Our study indicates that SAP of final-year medical students is appreciated by
patients with high overall quality of care and patient-centeredness.
PMID- 29347875
TI - Universal informative CpG sites for inferring tumor purity from DNA methylation
microarray data.
AB - Tumor purity is an intrinsic property of tumor samples and potentially has severe
impact on many types of data analysis. We have previously developed a statistical
method, InfiniumPurify, which could infer purity of a tumor sample given its
tumor type (available in TCGA) or a set of informative CpG (iDMC) sites. However,
in many clinical practices, researchers may focus on a specific type of tumor
samples that is not included in TCGA, and samples which are too few to identify
reliable iDMCs. This greatly restricts the application of InfiniumPurify in
cancer research. In this paper, we proposed an updated version of InfiniumPurify
(termed as uiInfiniumPurify) through identifying a universal set of iDMCs
(uiDMCs) and redesigning the algorithm to determine hyper- and hypo-methylation
status of each uiDMC. Through the application, we estimated tumor purities of
8830 tumor samples from TCGA. Result shows that our estimates are highly
consistent with those by other available methods. Consequently, the updated
uiInfiniumPurify, can be applied to a single sample (or a few samples) of
interest whose tumor type is not included in TCGA. This characteristic will
greatly broaden the application of uiInfiniumPurify in cancer research.
PMID- 29347877
TI - Part-set cueing impairment & facilitation in semantic memory.
AB - The present study explored the influence of part-set cues in semantic memory
using tests of "free" recall, reconstruction of order, and serial recall. Nine
distinct categories of information were used (e.g., Zodiac signs, Harry Potter
books, Star Wars films, planets). The results showed part-set cueing impairment
for all three "free" recall sets, whereas part-set cueing facilitation was
evident for five of the six ordered sets. Generally, the present results parallel
those often observed across episodic tasks, which could indicate that similar
mechanisms contribute to part-set cueing effects in both episodic and semantic
memory. A novel anchoring explanation of part-set cueing facilitation in order
and spatial tasks is provided.
PMID- 29347876
TI - Risk of overhydration and low lean tissue index as measured using a body
composition monitor in patients on hemodialysis: a systemic review and meta
analysis.
AB - Overhydration and sarcopenia, related to an individual's nutritional status, have
been associated with increased cardiovascular mortality and poor prognosis in
patients on hemodialysis. The purpose of this study was to investigate the
prediction of overhydration and sarcopenia on mortality in patients on
hemodialysis using a body composition monitor. We conducted a systematic review
and meta-analysis using a random-effects model. We searched the Cochrane Central
Register, OVID MEDLINE, EMBASE and PubMed databases for all studies published
prior to December 9, 2016 and reviewed the reference lists of relevant reviews,
registered trials and relevant conference proceedings. The overhydration group
(fluid excess, >15% vs. the normohydration group) and the low lean tissue index
group ( <10%) were compared with a reference group. Six trials, consisting of
29,469 patients, were included in the pooled analysis. The pooled hazard ratio
for overall survival of the overhydration group, compared with the reference
normohydration group was 1.798 (95% confidence interval [CI]: 1.53-2.804, p =
.001). The hazard ratio for mortality in the low lean tissue index group was
1.533 (95% CI, 1.411-1.644; p = .001) in the random-effects model. The results
from the most recent study showed the greatest heterogeneity in the sensitivity
analysis. Low lean tissue index and overhydration, measured using a body
composition monitor, were associated with a high mortality rate in patients on
hemodialysis.
PMID- 29347878
TI - The effect of aging on the (mis)perception of intentionality - an ERP study.
AB - Despite the accumulated knowledge on moral decision-making in the early stages of
development, empirical evidence is still limited in the old-aged adults. The
current study contributes to unveil the neural correlates of judgments of moral
transgressions as a function of aging, by examining the temporal dynamics of
neural activation elicited by intentional and accidental harmful actions in three
groups of healthy participants: young adults (18-35), adults (40-55), and older
adults (60-75). Older adults were slower and less accurate in rating
intentionality, compared to the younger groups. In ERP analysis, the older group
showed increased P2 amplitude, which was predicted by poorer performance on
neuropsychological tests. Reduced amplitudes were found on critical ERP
components to moral cognition (N2 and LPP), namely while processing intentional
harmful scenarios. Older adults seem to allocate more attentional resources (P2)
to the task, probably to compensate the age-related decline in executive
functioning, while younger groups show a pronounced negativity while detecting
harm (N2) and increased neural activation to encode the intentions behind the
acts (LPP).
PMID- 29347879
TI - The Listener Sets the Tone: High-Quality Listening Increases Attitude Clarity and
Behavior-Intention Consequences.
AB - We examined how merely sharing attitudes with a good listener shapes speakers'
attitudes. We predicted that high-quality (i.e., empathic, attentive, and
nonjudgmental) listening reduces speakers' social anxiety and leads them to delve
deeper into their attitude-relevant knowledge (greater self-awareness). This,
subsequently, differentially affects two components of speaker's attitude
certainty by increasing attitude clarity, but not attitude correctness. In
addition, we predicted that this increased clarity is followed by increased
attitude- expression intentions, but not attitude- persuasion intentions. We
obtained consistent support for our hypotheses across five experiments (including
one preregistered study), manipulating listening behavior in a variety of ways.
This is the first evidence that an interpersonal variable, unrelated to the
attitude itself, can affect attitude clarity and its consequences.
PMID- 29347880
TI - Functions of Utopia: How Utopian Thinking Motivates Societal Engagement.
AB - Images of ideal societies, utopias, are all around us; yet, little is known of
how utopian visions affect ordinary people's engagement with their societies. As
goals for society, utopias may elicit processes of collective self-regulation, in
which citizens are critical of, or take action to change, the societies they live
in. In three studies, we investigated the psychological function of utopian
thinking. In Study 1, measured utopianism was correlated with the activation of
three utopian functions: change, critique, and compensation. In Study 2, primed
utopian thinking consistently enhanced change and criticism intentions. Study 3
also provided evidence that mental contrasting-first imagining a utopian vision
and then mentally contrasting the current society to this vision-underlies the
facilitative effect of utopian thinking on societal engagement.
PMID- 29347881
TI - Being an agent of change: a student's view of the UK's first yearlong
Longitudinal Integrated Clerkship (LIC).
PMID- 29347882
TI - Third Shade of Simulation.
PMID- 29347883
TI - Pulmonary Laser Metastasectomy by 1318-nm Neodymium-Doped Yttrium-Aluminum Garnet
Laser: A Retrospective Study About Laser Metastasectomy of the Lung.
AB - BACKGROUND: The lungs are among the first organ affected by remote metastases
from many primary tumors. The surgical resection of isolated pulmonary metastases
represents an important and effective element of therapy. This is a retrospective
study about our entire experience with pulmonary resection for metastatic cancer
using 1318-nm neodymium-doped yttrium-aluminum garnet laser. METHOD: In this
single-institution study, we retrospectively analyzed a group of 209 patients
previously treated for primary malignant solid tumors. We excluded 103 patients.
The number and location of lesions in the lungs was determined using chest
computed tomography and positron emission tomography-computed tomography.
Disseminated malignancy was excluded. All pulmonary laser resections are
performed via an anteroaxillary muscle-sparing thoracotomy. All lesions were
routinely removed by laser with a small (5-10 mm) margin of the healthy lung.
Patients received systematic lymph node sampling with intraoperative smear
cytology of sampled lymph nodes. RESULTS: Mortality at 2 years from the first
surgery is around 20% (10% annually). This value increases to 45% in the third
year. The estimated median survival for patients who underwent the first surgery
is reported to be approximately 42 months. CONCLUSION: Our results show that
laser resection of lung metastases can achieve good result, in terms of radical
resection and survival, as conventional surgical metastasectomy. The great
advantage is the possibility of limiting the damage to the lung. Stapler
resection of a high number of metastases would mutilate the lung.
PMID- 29347884
TI - Differential mRNA expression of inflammasome genes NLRP1 and NLRP3 in abdominal
aneurysmal and occlusive aortic disease.
AB - NLRP1 and NLRP3 inflammasomes might differentially mediate the chronic
inflammatory response in abdominal aortic aneurysm (AAA) and aortic occlusive
disease (AOD). We measure differential relative gene expression of NLRP1 and
NLRP3 inflammasomes in aortic tissues from 30 patients undergoing AAA open repair
compared to aortic biopsies from 30 patients undergoing surgery to treat AOD.
Aortic wall samples from autopsy without aortic disease were used as controls.
NLRP3 was overexpressed in patients with AAA and AOD (RQ 1.185 +/- 0.15, and
1.098 +/- 0.05, respectively) compared to donors (RQ 1.001 +/- 0.08) (OR 2.8, 95%
CI 1.2-4.3, p < 0.05 for AAA and OR 2.1, 95% CI 1.1-3.8, p < 0.05 for AOD). NLRP1
gene expression was significantly upregulated in patients with AOD (RQ 1.197 +/-
0.09). Meanwhile, NLRP1 was normal expressed in AAA (RQ 1.003 +/- 0.07) as well
as in autopsy aortic specimens (RQ 1.005 +/- 0.11). Enhanced NLRP1 expression in
AOD was even significant when compared to AAA (OR 2.3, 95% CI 1.2-3.3, p < 0.05)
or controls (OR 2.2, 95% CI 1.1-3.1, p < 0.05). According to our findings, NLRP3
could be involved in the common etiology of AAA and AOD, whereas NLRP1 appears to
have a specific role in AOD development.
PMID- 29347885
TI - Preparation of affordable and multifunctional clay-based ceramic filter matrix
for treatment of drinking water.
AB - Affordable clay-based ceramic filters with multifunctional properties were
prepared using low-cost and active ingredients. The characterization results
clearly revealed well crystallinity, structural elucidation, extensive porosity,
higher surface area, higher stability, and durability which apparently enhance
the treatment efficiency. The filtration rates of ceramic filter were evaluated
under gravity and the results obtained were compared with a typical gravity slow
sand filter (GSSF). All ceramic filters showed significant filtration rates of
about 50-180 m/h, which is comparatively higher than the typical GSSF. Further,
purification efficiency of clay-based ceramic filters was evaluated by
considering important drinking water parameters and contaminants. A significant
removal potential was achieved by the clay-based ceramic filter with 25% and 30%
activated carbon along with active agents. Desired drinking water quality
parameters were achieved by potential removal of nitrite (98.5%), nitrate
(80.5%), total dissolved solids (62%), total hardness (55%), total organic
pollutants (89%), and pathogenic microorganisms (100%) using ceramic filters
within a short duration. The remarkable purification and disinfection
efficiencies were attributed to the extensive porosity (0.202 cm3 g-1), surface
area (124.61 m2 g-1), stability, and presence of active nanoparticles such as Cu,
TiO2, and Ag within the porous matrix of the ceramic filter.
PMID- 29347886
TI - The Role of Place Cues in Voluntary Stream Segregation for Cochlear Implant
Users.
AB - Sequential stream segregation by cochlear implant (CI) listeners was investigated
using a temporal delay detection task composed of a sequence of regularly
presented bursts of pulses on a single electrode (B) interleaved with an
irregular sequence (A) presented on a different electrode. In half of the trials,
a delay was added to the last burst of the regular B sequence, and the listeners
were asked to detect this delay. As a jitter was added to the period between
consecutive A bursts, time judgments between the A and B sequences provided an
unreliable cue to perform the task. Thus, the segregation of the A and B
sequences should improve performance. In Experiment 1, the electrode separation
and the sequence duration were varied to clarify whether place cues help CI
listeners to voluntarily segregate sounds and whether a two-stream percept needs
time to build up. Results suggested that place cues can facilitate the
segregation of sequential sounds if enough time is provided to build up a two
stream percept. In Experiment 2, the duration of the sequence was fixed, and only
the electrode separation was varied to estimate the fission boundary. Most
listeners were able to segregate the sounds for separations of three or more
electrodes, and some listeners could segregate sounds coming from adjacent
electrodes.
PMID- 29347874
TI - Adjunctive Glucocorticoid Therapy in Patients with Septic Shock.
AB - BACKGROUND: Whether hydrocortisone reduces mortality among patients with septic
shock is unclear. METHODS: We randomly assigned patients with septic shock who
were undergoing mechanical ventilation to receive hydrocortisone (at a dose of
200 mg per day) or placebo for 7 days or until death or discharge from the
intensive care unit (ICU), whichever came first. The primary outcome was death
from any cause at 90 days. RESULTS: From March 2013 through April 2017, a total
of 3800 patients underwent randomization. Status with respect to the primary
outcome was ascertained in 3658 patients (1832 of whom had been assigned to the
hydrocortisone group and 1826 to the placebo group). At 90 days, 511 patients
(27.9%) in the hydrocortisone group and 526 (28.8%) in the placebo group had died
(odds ratio, 0.95; 95% confidence interval [CI], 0.82 to 1.10; P=0.50). The
effect of the trial regimen was similar in six prespecified subgroups. Patients
who had been assigned to receive hydrocortisone had faster resolution of shock
than those assigned to the placebo group (median duration, 3 days [interquartile
range, 2 to 5] vs. 4 days [interquartile range, 2 to 9]; hazard ratio, 1.32; 95%
CI, 1.23 to 1.41; P<0.001). Patients in the hydrocortisone group had a shorter
duration of the initial episode of mechanical ventilation than those in the
placebo group (median, 6 days [interquartile range, 3 to 18] vs. 7 days
[interquartile range, 3 to 24]; hazard ratio, 1.13; 95% CI, 1.05 to 1.22;
P<0.001), but taking into account episodes of recurrence of ventilation, there
were no significant differences in the number of days alive and free from
mechanical ventilation. Fewer patients in the hydrocortisone group than in the
placebo group received a blood transfusion (37.0% vs. 41.7%; odds ratio, 0.82;
95% CI, 0.72 to 0.94; P=0.004). There were no significant between-group
differences with respect to mortality at 28 days, the rate of recurrence of
shock, the number of days alive and out of the ICU, the number of days alive and
out of the hospital, the recurrence of mechanical ventilation, the rate of renal
replacement therapy, and the incidence of new-onset bacteremia or fungemia.
CONCLUSIONS: Among patients with septic shock undergoing mechanical ventilation,
a continuous infusion of hydrocortisone did not result in lower 90-day mortality
than placebo. (Funded by the National Health and Medical Research Council of
Australia and others; ADRENAL ClinicalTrials.gov number, NCT01448109 .).
PMID- 29347887
TI - Cryo-Assisted Resection En Bloc, and Cryoablation In Situ, of Primary Breast
Cancer Coupled With Intraoperative Ultrasound-Guided Tracer Injection: A
Preliminary Clinical Study.
AB - The aim of the study was to perform cryosurgery on a primary breast tumor,
coupled with simultaneous peritumoral and intratumoral tracer injection of a blue
dye, to evaluate lymphatic mapping. We explored the ability of our strategy to
prevent tumor cells, but not that of injected tracers, to migrate to the
lymphovascular drainage during conventional resection of frozen breast
malignancies. Seventeen patients aged 51 (14) years (mean [standard deviation]),
presenting primary breast cancer with stage I to IV, were randomly selected and
treated in The Rudolfinerhaus Private Clinic in Vienna, Austria, and included in
this preliminary clinical study. Under intraoperative ultrasound, 14 patients
underwent curative cryo-assisted tumor resection en bloc, coupled with
peritumoral tracer injection, which consisted of complete tumor freezing and
concomitant peritumor injection with a blue dye, before resection and sentinel
lymph node dissection (group A). Group B consists of 3 patients previously
refused any standard therapy and had palliative tumor cryoablation in situ
combined with intratumoral tracer injection. The intraoperative ultrasound
facilitated needle positioning and dye injection timing. In group A, the frozen
site extruded the dye that was distributed through the unfrozen tumor, the breast
tissue, and the resection cavity for 12 patients. One to 4 lymph nodes were
stained for 10 of 14 patients. The resection margin was evaluable. Our
intraoperative ultrasound-guided performance revealed the injection and migration
of a blue dye during the frozen resection en bloc and cryoablation in situ of
primary breast tumors. Sentinel lymph node mapping, pathological determination of
the tumor, and resection margins were achievable. The study paves the way for
intraoperative cryo-assisted therapeutic strategies for breast cancer.
PMID- 29347888
TI - Patient baseline interpersonal problems as moderators of outcome in two
psychotherapies for bulimia nervosa.
AB - OBJECTIVE: We tested an aptitude by treatment interaction; namely, whether
patients' baseline interpersonal problems moderated the comparative efficacy of
cognitive-behavioral therapy (CBT) vs. interpersonal psychotherapy (IPT) for
bulimia nervosa (BN). METHOD: Data derived from a randomized-controlled trial.
Patients reported on their interpersonal problems at baseline; purge frequency at
baseline, midtreatment, and posttreatment; and global eating disorder severity at
baseline and posttreatment. We estimated the rate of change in purge frequency
across therapy, and the likelihood of attaining clinically meaningful improvement
(recovery) in global eating disorder severity by posttreatment. We then tested
the interpersonal problem by treatment interactions as predictors of both
outcomes. RESULTS: Patients with more baseline overly communal/friendly problems
showed steeper reduction in likelihood of purging when treated with CBT vs. IPT.
Patients with more problems of being under communal/cold had similar reductions
in likelihood of purging across both treatments. Patients with more baseline
problems of being overly agentic were more likely to recover when treated with
IPT vs. CBT, whereas patients with more problems of being under agentic were more
likely to recover when treated with CBT vs. IPT. CONCLUSIONS: Interpersonal
problems related to communion and agency may inform treatment fit among two
empirically supported therapies for BN.
PMID- 29347889
TI - Allostery in Orai1 binding to calmodulin revealed from conformational
thermodynamics.
AB - Here, we study microscopic mechanism of complex formation between Ca2+-bound
calmodulin (holoCaM) and Orai1 that regulates Ca2+-dependent inactivation process
in eukaryotic cells. We compute conformational thermodynamic changes in holoCaM
with respect to complex of Orai1 bound to C-terminal domain of holoCaM using
histograms of dihedral angles of the proteins over trajectories from molecular
dynamics simulations. Our analysis shows that the N-terminal domain residues L4,
T5, Q41, N42, T44 and E67 of holoCaM get destabilized and disordered due to Orai1
binding to C-terminal domain of calmodulin affect the N-terminal domain residues.
Among these residues, polar T44, having maximum destabilization and disorder via
backbone fluctuations, shows the largest change in solvent exposure. This
suggests that N-terminal domain is allosterically regulated via T44 by the
binding of Orai1 to the C-terminal domain.
PMID- 29347890
TI - Disproportionately higher unintentional injury mortality among Alaska Native
people, 2006-2015.
AB - We compared rates of unintentional injury (UI) deaths (total and by injury
category) among Alaska Native (AN) people to rates of U.S. White (USW) and Alaska
White (AKW) populations during 2006-2015. The mortality data for AN and AKW
populations were obtained from Alaska Bureau of Vital Statistics and USW
mortality data were obtained from WISQARS, the Center for Disease Control and
Prevention online injury data program. AN and AKW rates were age-adjusted to the
U.S. 2000 Standard Population and rate ratios (RR) were calculated. AN people had
higher age-adjusted total UI mortality than the USW (RR = 2.6) and AKW (RR = 2.3)
populations. Poisoning was the leading cause of UI death among AN people (35.9
per 100,000), more than twice that of USW (RR = 2.9) and AKW (RR = 2.5). Even
greater disparities were found between AN people and USW for: natural environment
(RR = 20.7), transport-other land (RR = 12.4), and drowning/submersion (RR =
9.1). Rates of AN UI were markedly higher than rates for either USW or AKW.
Identifying all the ways in which alcohol/drugs contribute to UI deaths would aid
in prevention efforts. All transportation deaths should be integrated into one
fatality rate to provide more consistent comparisons between groups.
PMID- 29347891
TI - Changing character: A narrative review of personality change in psychotherapies
for personality disorder.
AB - OBJECTIVE: Personality disorder (PD) is a negative prognostic indicator for
treatment, and absolute improvements in functioning among these patients are
often modest. This may be because personality features that give rise to
dysfunction in PD are not targeted optimally during most treatments. METHOD:
Attachment, mentalization, core beliefs, and personality organization/defense use
were identified as personality constructs that have been pursued in treatment
studies and that are proposed to underlie PD. RESULTS: All constructs correlate
with psychiatric symptoms, PD diagnosis, and functioning. Defense mechanisms and
core beliefs further distinguish specific PDs, whereas personality organization
separates more versus less severe PDs. Evidence from treatment and naturalistic
studies indicate that maturation of defense mechanisms temporally precedes
improvements in symptoms and functioning. Changes in attachment and mentalization
correlate with some outcomes, but mediation of improvement has not been
established. In psychodynamic therapy, transference interpretations may promote
amelioration of personality dysfunction. With the exception of attachment, the
experimental literature is lacking that could explicate the mechanisms by which
these personality constructs maintain psychosocial dysfunction. CONCLUSIONS:
Future research should aim to identify changes in these mechanisms that mediate
positive outcomes in PD, as well as the specific therapeutic procedures that best
promote positive change in PD.
PMID- 29347892
TI - Pilot study on the use of data mining to identify cochlear implant candidates.
AB - OBJECTIVES: The goal of this pilot study was to determine the clinical utility of
data-mining software that screens for cochlear implant (CI) candidacy. METHODS:
The Auditory Implant Initiative developed a software module that screens for CI
candidates via integration with a software system (Noah 4) that serves as a
depository for hearing test data. To identify candidates, patient audiograms from
one practice were exported into the screening module. Candidates were tracked to
determine if any eventually underwent implantation. RESULTS: After loading 4836
audiograms from the Noah 4 system, the screening module identified 558 potential
CI candidates. After reviewing the data for the potential candidates, 117 were
targeted and invited to an educational event. Following the event, a total of six
candidates were evaluated, and two were implanted. DISCUSSION: This objective
approach to identifying candidates has the potential to address the gross
underutilization of CIs by removing any bias or lack of knowledge regarding the
management of severe to profound sensorineural hearing loss with CIs. CONCLUSION:
The screening module was an effective tool for identifying potential CI
candidates at one ENT practice. On a larger scale, the screening module has the
potential to impact thousands of CI candidates worldwide.
PMID- 29347893
TI - ["How Beautiful Must I be?"- Physical Attractiveness and Mental Health in
Adolescents].
AB - "How Beautiful Must I be?"- Physical Attractiveness and Mental Health in
Adolescents Physical attractiveness is a high priority for young people. The
beauty ideals and presentations spread in the media often reinforce self-doubt
and self-insecurity. In 730 adolescents (age 13 to 20 years) it was measured, how
they experience appearance-related social pressure (FASD), the extent to which
physical deficits are perceived (BDDQ), and how these features are related to
mental symptoms (SDQ). The results demonstrate that young people are very
concerned about their appearance (30.7 %) and are overly concerned with perceived
physical defects (29.5 %). In addition, there is a strong appearance-related
social pressure through peers and parents. The young people particularly affected
in these areas report more emotional and behavioral problems. The results suggest
that attention should be given to physical self-assessment as an important factor
in diagnosis and therapy.
PMID- 29347894
TI - [Gender-specific Differences in the Degree of Burden on Children and Adolescents
Taken into Custody].
AB - Gender-specific Differences in the Degree of Burden on Children and Adolescents
Taken into Custody Children and adolescents who were taken into care are a high
risk group for mental disorders such as externalizing problems or conduct
disorders. 95 children and adolescents who were taken into care were tested with
the Screening Child Trauma Questionnaire (CTQ) and the Massachusetts Youth
Screening Instrument 2 (MAYSI-2). In a large proportion of those children and
adolescents emotional and physical neglect and abuse was identified. There were
sex differences in suicidal thoughts, somatoform disorders, and emotional abuse.
The knowledge of mental disorders as well as the gender-specific characteristics
is important for specialists of inhospital institutions, in order to optimize
their quality of care.
PMID- 29347895
TI - [Childhood Experiences of Adolescents in Boarding Schools. A Comparison with
Adolescents in Residential Care and with the General Population].
AB - Childhood Experiences of Adolescents in Boarding Schools. A Comparison with
Adolescents in Residential Care and with the General Population Various studies
indicate that students in boarding schools experience a lot of violence during
their accommodation. However, it is not proved whether adolescents in boarding
schools are also a burdensome group regarding early childhood experiences such as
neglect and abuse. The aim of the study was to find out more about the
experiences of adolescents in boarding schools and to determine whether there are
differences between adolescents in residential care and between the general
population. Furthermore, it should be examined whether boys and girls differ in
their experiences. In the study, adolescents of boarding schools and of
residential care all over Germany, starting at the age of 15 (n = 322), were
asked regarding physical and emotional neglect/abuse, light/severe parent
violence, negative/positive educational behavior of the parents. The results show
that students in boarding schools were less likely to be affected by childhood
maltreatment and more likely to have experienced positive parental behavior
compared to children in residential care. Compared to the general population,
students in boarding schools were more often and more severely affected by
parental violence. Moreover, girls had experienced parental violence more often
than boys. The results indicate that in boarding schools there is a need for
support offers for adolescents with a history of violent experiences and that the
risk group should be identified directly at the admission to the school.
PMID- 29347896
TI - [Impact of Different Types of Fathers on Family Climate in Young Adulthood: A
Multi-perspective Longitudinal Study on 14 to 27 Year Olds and their Fathers].
AB - Impact of Different Types of Fathers on Family Climate in Young Adulthood: A
Multi-perspective Longitudinal Study on 14 to 27 Year Olds and their Fathers In a
13 year longitudinal study, the influence of three types of fathers on the family
climate was analyzed. In a sample of 213 subjects, their 169 fathers and their
210 mothers, the family environment ( Family Environment Scales) was examined
when the subjects were young adults (M = 26.89, SD = 1.32). The results of the
study point to significant changes in family climate in those young adults who
described their father as increasingly negative (N = 28) or distant (N = 11) when
in adolescence. These two groups showed a more negative family environment and
greater differences between the perspectives of fathers and their young adult
children than the group of young adults who described their father as normative
(N = 174) when in adolescence. The highest discrepancies were described by young
adults with a negative relationship with their father in adolescence. The
findings show a long lasting importance of father-child interactions in
adolescence.
PMID- 29347898
TI - ?
PMID- 29347897
TI - [Effects of Bilingualism on Cognitive Functions in Early Childhood].
AB - Effects of Bilingualism on Cognitive Functions in Early Childhood Studies have
revealed advantages in cognitive functions among children with bilingualism. In
this study we investigate cognitive functions in monolingual and bilingual
preschool children taking socioeconomic status into account. The study population
consists of 40 monolingual (German) children (Mage = 5.0 +/- 0.4) and 23
bilingual (German/English) children (Mage = 5.1 +/- 0.6). A neuropsychological
test battery was conducted. The analyses revealed better performance for
bilingual children. However, significant group differences were only found with
respect to phonological short-term memory. Controlling for socioeconomic status,
intelligence and balanced bilingualism, only slight advantages in cognitive
performance were found for bilingual children. Due to high socioeconomic status
in both groups, we suppose a ceiling effect. Children's development might be
extensively promoted in upper class families and therefore bilingualism may not
have additional impact on cognitive functions in these children.
PMID- 29347899
TI - [Congress Dates].
PMID- 29347900
TI - [Authors].
PMID- 29347901
TI - [Test Reviews].
PMID- 29347903
TI - Child, Caregiver, and Health Care Provider Perspectives and Experiences Regarding
Disclosure of HIV Status to Perinatally Infected Children in Lima, Peru.
AB - BACKGROUND: Despite recommendations for disclosure of HIV status to children
living with HIV (CLHIV), fewer than half of CLHIV at the Instituto Nacional de
Salud del Nino (INSN) in Lima, Peru, have had disclosure. How and when the
disclosure process for CLHIV should take place in Peru has not been studied.
METHODS: We conducted a qualitative study at INSN to explore perceptions and
experiences of 6 health care providers (HCPs), 14 disclosed and nondisclosed
CLHIV (8-17 years), and their 14 caregivers regarding knowledge of illness,
disclosure of HIV status, and appropriate disclosure approaches. RESULTS:
Disclosed children wanted to be told their diagnosis earlier. Nondisclosed
children expressed frustration taking medications. Caregivers and HCPs discussed
motivations to disclose, including educating, honesty, improving medication
adherence, and preventing secondary transmission. CONCLUSION: Culturally
appropriate guidelines and training for HCPs and caregivers are needed to support
disclosure of children's HIV status and ongoing support for CLHIV.
PMID- 29347904
TI - Social skills training and play group intervention for children with oppositional
defiant disorders/conduct disorder: Mediating mechanisms in a head-to-head
comparison.
AB - OBJECTIVE: Social-cognitive information processing, social skills, and social
interactions are problem-maintaining variables for aggressive behavior in
children. We hypothesized that these factors may be possible mediators of the
mechanism of change in the child-centered treatment of conduct disorders (CDs).
The aim of the present study (Clinical trials.gov Identifier: NCT01406067) was to
examine putative mechanisms of change for the decrease in oppositional-defiant
behavior resulting from child-centered treatment of patients with oppositional
defiant disorder (ODD) or CD. METHOD: 91 children (age 6-12 years) with ODD/CD
were randomized to receive either social skills training or to a resource
activating play group. Mediator analyses were conducted using path analyses.
RESULTS: The assumed mediating effects were not significant. However, alternative
models with the putative mediators and outcome in reversed positions showed
significant indirect effects of the oppositional-defiant symptoms as mediator for
the decrease of disturbance of social-information processing, social skills, and
social interactions. CONCLUSIONS: The proposed model for mechanisms of change
could not be confirmed, with the results pointing to a reversed causality.
Variables other than those hypothesized must be responsible for mediating the
effects of the intervention on child oppositional-defiant behavior. Possible
mechanisms of change were discussed.
PMID- 29347905
TI - Synthesize of silver-nanoparticles by plant extract and its application for
preconcentration of cadmium followed by flame atomic absorption spectrometry.
AB - In this paper, Mentha pulegium leaves extract was used as a green reducing agent
for the synthesis of silver-nanoparticles. The synthesized silver-nanoparticles
were characterized by UV-VIS spectrophotometry, transmission electron microscopy,
X-ray spectroscopy and used as an adsorbent for preconcentration of trace levels
of cadmium (II). After the desorption of cadmium (II) in 5 mol L-1 formic acid,
the desorbent solution was aspirated into the flame atomic absorption
spectrometry for the determination of cadmium. In order to optimize the
experimental condition, a response surface methodology based on central composite
design was used. The optimum conditions are: pH: 8.6, amounts of adsorbent: 30
mg, 10 min extraction time and desorption time of 2 min. Under the optimum
condition, the calibration curve was linear in the range of 5-200 MUg L-1 cadmium
(II) ion with a correlation coefficient of 0.9995. The limit of detection was 1.1
MUg L-1 and the relative standard deviation for 25 MUg L-1 cadmium (II) ion was
3.0% (n = 5). In order to check the applicability of the proposed method,
different real samples were analyzed. Also, the accuracy of this method was
successfully checked by the analysis of certified reference material and spike
tests.
PMID- 29347906
TI - Expression and functional analysis of the Propamocarb-related gene CsDIR16 in
cucumbers.
AB - BACKGROUND: Cucumber downy mildew is among the most important diseases that can
disrupt cucumber production. Propamocarb, also known as propyl-[3
(dimethylamino)propyl]carbamate (PM), is a systemic carbamate fungicide pesticide
that is widely applied in agricultural production because of its high efficiency
of pathogens control, especially cucumber downy mildew. However, residual PM can
remain in cucumbers after the disease has been controlled. To explore the
molecular mechanisms of PM retention, cucumber cultivars 'D9320' (with the
highest residual PM content) and 'D0351' (lowest residual PM content) were
studied. High-throughput tag-sequencing (Tag-Seq) results showed that the CsDIR16
gene was related to PM residue, which was verified using transgenic technology.
RESULTS: We investigated the activity of a dirigent cucumber protein encoded by
the CsDIR16 in gene response to stress induced by PM treatment. Gene-expression
levels of CsDIR16 were up-regulated in the fruits, leaves, and stems of 'D0351'
plants in response to PM treatment. However, in cultivar 'D9320', CsDIR16 levels
were down-regulated in the leaves and stems after PM treatment, with no
statistically significant differences observed in the fruits. Induction by
jasmonic acid, abscisic acid, polyethylene glycol 4000, NaCl, and Corynespora
cassiicola Wei (Cor) resulted in CsDIR16 up-regulation in 'D0351' and 'D9320'.
Expression after salicylic acid treatment was up-regulated in 'D0351', but was
down-regulated in 'D9320'. CsDIR16 overexpression lowered PM residues, and these
were more rapidly reduced in CsDIR16(+) transgenic 'D9320' plants than in wild
type 'D9320' and CsDIR16(-) transgenic plants. CONCLUSIONS: Analyses of the
CsDIR16-expression patterns in the cucumber cultivars with the highest and lowest
levels of PM residue, and transgenic validation indicated that CsDIR16 plays a
positive role in reducing PM residues. The findings of this study help understand
the regulatory mechanisms occurring in response to PM stress in cucumbers and in
establishing the genetic basis for developing low-pesticide residue cucumber
cultivars.
PMID- 29347907
TI - Blood lactate is a predictor of short-term mortality in patients with myocardial
infarction complicated by heart failure but without cardiogenic shock.
AB - BACKGROUND: Mortality in patients with acute myocardial infarction (AMI) has
improved substantially with modern therapy including percutaneous coronary
interventions (PCI) but remains high in certain subgroups such as patients
presenting with overt cardiogenic shock. However, the risk for AMI in patients
presenting acutely with signs of heart failure but without cardiogenic shock is
less well described. We aimed to identify risk factors for mortality in AMI
patients with heart failure without overt cardiogenic shock. METHODS: Using data
from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR), we
identified patients with operator-registered heart failure (Killip class II-IV),
and evaluated predictors of mortality based on clinical factors from review of
patient records. RESULTS: A total of 1260 unique patients with acute myocardial
infarction underwent PCI in 2014, of which 77 patients (7%) showed signs of heart
failure (Killip II-IV) Overall 30-day mortality in patients with Killip class II
IV was 20% (N = 15). In patients classified Killip IV (1%), 30-day mortality was
50% (N = 6). In patients presenting with mild to moderate heart failure (Killlip
class II-III), 30-day mortality was 14% (N = 9). In patients with Killip class II
III, lactate >=2.5 mmol/L was associated with 30-day mortality, whereas systolic
blood pressure < 90 mmHg, age, sex and BMI were not. In patients with lactate <
2.5 mmol/L 30-day mortality was 5% (N = 2) whereas mortality was 28% (N = 7) with
lactate >=2.5 mmol/L. This cut-off provided discriminative information on 30-day
mortality (area under ROC curve 0.74). CONCLUSIONS: In patients with AMI and
signs of mild to moderate heart failure, lactate >=2.5 mmol/L provides additional
prognostic information. Interventions to reduce risk may be targeted to these
patients.
PMID- 29347908
TI - Management and outcomes of patients presenting with sepsis and septic shock to
the emergency department during nursing handover: a retrospective cohort study.
AB - BACKGROUND: Clinical handover is an important process for the transition of
patient-care responsibility to the next healthcare provider, but it may divert
the attention of the team away from active patients. This is challenging in the
Emergency Department (ED) because of highly dynamic patient conditions and is
likely relevant in conditions that requires time-sensitive therapies, such as
sepsis. We aimed to examine the management and outcomes of patients presenting
with sepsis and septic shock to the ED during nursing handover. METHODS: This
retrospective cohort study was conducted at a 115-bed ED and more than 200,000
annual ED visits, within a 900-bed academic tertiary care center. Data on
Surviving Sepsis Campaign (SSC) bundle elements and hospital mortality were
collected for all >=14-year-old patients who presented to the ED with a diagnosis
of sepsis and septic shock between January 1, 2011 and October 30, 2013. Our
primary outcome was time to antibiotics, were other SSC bundle elements and
mortality counted as secondary outcomes. Patients were divided into two groups:
1) handover time group, comprising patients who presented an hour before or after
the start of handover time (6-8 AM/PM), and 2) non-handover time group,
comprising patients who presented over the remaining 20 h. RESULTS: During the
study period, 1330 patients presented with sepsis or septic shock (228, handover
time group; 1102, non-handover time group). No significant differences were found
between the handover time and non-handover time groups, respectively, in median
time to antibiotic administration (100 [interquartile range (IQR) 57-172] vs. 95
[IQR 50-190] minutes; P = 0.07), median time to serum lactate result (162 [IQR
108-246] vs. 156 [IQR 180-246] minutes; P = 0.33) and median time to obtain blood
culture (54 [IQR 36-119] vs. 52 [IQR 28-103] minutes; P = 0.52), and hospital
mortality rate (29.4% vs. 28.9%; P = 0.89). CONCLUSION: No significant
differences were found in median time of SSC bundle elements or hospital
mortality between patients who presented during the handover and non-handover
times.
PMID- 29347910
TI - Getting messier with TIDieR: embracing context and complexity in intervention
reporting.
AB - BACKGROUND: The Template for Intervention Description and Replication (TIDieR)
checklist and guide was developed by an international team of experts to promote
full and accurate description of trial interventions. It is now widely used in
health research. The aim of this paper is to describe the experience of using
TIDieR outside of trials, in a range of applied health research contexts, and
make recommendations on its usefulness in such settings. MAIN BODY: We used the
TIDieR template for intervention description in six applied health research
projects. The six cases comprise a diverse sample in terms of clinical problems,
population, settings, stage of intervention development and whether the
intervention was led by researchers or the service deliverers. There was also
variation in how the TIDieR description was produced in terms of contributors and
time point in the project. Researchers involved in the six cases met in two
workshops to identify issues and themes arising from their experience of using
TIDieR. We identified four themes which capture the difficulties or complexities
of using TIDieR in applied health research: (i) fidelity and adaptation: all
aspects of an intervention can change over time; (ii) voice: the importance of
clarity on whose voice the TIDieR description represents; (iii) communication
beyond the immediate context: the usefulness of TIDieR for wider dissemination
and sharing; (iv) the use of TIDieR as a research tool. CONCLUSION: We found
TIDieR to be a useful tool for applied research outside the context of clinical
trials and we suggest four revisions or additions to the original TIDieR which
would enable it to better capture these complexities in applied health research:
An additional item, 'voice' conveys who was involved in preparing the TIDieR
template, such as researchers, service users or service deliverers. An additional
item, 'stage of implementation' conveys what stage the intervention has reached,
using a continuum of implementation research suggested by the World Health
Organisation. A new column, 'modification' reminds authors to describe
modifications to any item in the checklist. An extension of the 'how well' item
encourages researchers to describe how contextual factors affected intervention
delivery.
PMID- 29347909
TI - Identification of minor effect QTLs for plant architecture related traits using
super high density genotyping and large recombinant inbred population in maize
(Zea mays).
AB - BACKGROUND: Plant Architecture Related Traits (PATs) are of great importance for
maize breeding, and mainly controlled by minor effect quantitative trait loci
(QTLs). However, cloning or even fine-mapping of minor effect QTLs is very
difficult in maize. Theoretically, large population and high density genetic map
can be helpful for increasing QTL mapping resolution and accuracy, but such a
possibility have not been actually tested. RESULTS: Here, we employed a
genotyping-by-sequencing (GBS) strategy to construct a linkage map with 16,769
marker bins for 1021 recombinant inbred lines (RILs). Accurately mapping of well
studied genes P1, pl1 and r1 underlying silk color demonstrated the map quality.
After QTL analysis, a total of 51 loci were mapped for six PATs. Although all of
them belong to minor effect alleles, the lengths of the QTL intervals, with a
minimum and median of 1.03 and 3.40 Mb respectively, were remarkably reduced as
compared with previous reports using smaller size of population or small number
of markers. Several genes with known function in maize were shown to be
overlapping with or close neighboring to these QTL peaks, including na1, td1, d3
for plant height, ra1 for tassel branch number, and zfl2 for tassel length. To
further confirm our mapping results, a plant height QTL, qPH1a, was verified by
an introgression lines (ILs). CONCLUSIONS: We demonstrated a method for high
resolution mapping of minor effect QTLs in maize, and the resulted comprehensive
QTLs for PATs are valuable for maize molecular breeding in the future.
PMID- 29347911
TI - microRNAs associated with early neural crest development in Xenopus laevis.
AB - BACKGROUND: The neural crest (NC) is a class of transitory stem cell-like cells
unique to vertebrate embryos. NC cells arise within the dorsal neural tube where
they undergo an epithelial to mesenchymal transition in order to migrate and
differentiate throughout the developing embryo. The derivative cell types give
rise to multiple tissues, including the craniofacial skeleton, peripheral nervous
system and skin pigment cells. Several well-studied gene regulatory networks
underpin NC development, which when disrupted can lead to various
neurocristopathies such as craniofrontonasal dysplasia, DiGeorge syndrome and
some forms of cancer. Small RNAs, such as microRNAs (miRNAs) are non-coding RNA
molecules important in post-transcriptional gene silencing and critical for
cellular regulation of gene expression. RESULTS: To uncover novel small RNAs in
NC development we used high definition adapters and next generation sequencing of
libraries derived from ectodermal explants of Xenopus laevis embryos induced to
form neural and NC tissue. Ectodermal and blastula animal pole (blastula) stage
tissues were also sequenced. We show that miR-427 is highly abundant in all four
tissue types though in an isoform specific manner and we define a set of 11
miRNAs that are enriched in the NC. In addition, we show miR-301a and miR-338 are
highly expressed in both the NC and blastula suggesting a role for these miRNAs
in maintaining the stem cell-like phenotype of NC cells. CONCLUSION: We have
characterised the miRNAs expressed in Xenopus embryonic explants treated to form
ectoderm, neural or NC tissue. This has identified novel tissue specific miRNAs
and highlighted differential expression of miR-427 isoforms.
PMID- 29347913
TI - An unusual case of infective pneumocephalus: case report of pneumocephalus
exacerbated by continuous positive airway pressure.
AB - BACKGROUND: Pneumocephalus, illustrated by air in the cranial vault is relatively
infrequent and generally associated with neurosurgery, trauma, meningitis and
barotrauma. However cases of spontaneous non-traumatic pneumocephalus remain
rare. While the relationship between continuous positive airway pressure (CPAP)
and atraumatic pneumocephalus has been previously reported, to our knowledge the
rare presentation associated with sinus wall osteomyelitis has never been
described. We summarize here the case of a 67-year-old woman's acute presentation
of Streptococcus salvarius infection after a sudden drop in her consciousness.
CASE PRESENTATION: The patient was brought to hospital by family reporting a one
week history of sudden deterioration, cognitive decline, and lethargy. The
patient presented with reduced arousal, cognitive function (Glasgow Coma Scale:
10, Abbreviated Mental Test Score:CS, 0 AMTS), and no history of trauma. Computed
Tomography (CT) imaging was ordered and identified a significant pneumocephalus
with no cranial defect. Further investigations acknowledged possible sinus or
middle ear disease, which was highlighted by the discovery of S. salivarius by
polymerase chain reaction (PCR) and potentially exacerbated by the use of
nocturnal continuous positive airway pressure (CPAP). The patient made a complete
recovery by eliminating likely causative factors and long term regimental
antibiotics administration. CONCLUSION: This case highlights a rare neurological
presentation of S. salivarius infection with a mixed aetiology of spontaneous
pneumocephalus. This case features an atypical complication associated with CPAP
use, and to our knowledge is the first case to be associated with sinus wall
osteomyelitis. Recognition of the clinical features and risk factors for
spontaneous pneumocephalus -while rare-serve to broaden our clinical index of
suspicion when presented with patients experiencing neurological deficit.
Information from this case may also aid in improving prevention, early diagnosis,
and future management.
PMID- 29347912
TI - Genome-wide analysis of the potato Hsp20 gene family: identification, genomic
organization and expression profiles in response to heat stress.
AB - BACKGROUND: Heat shock proteins (Hsps) are essential components in plant
tolerance mechanism under various abiotic stresses. Hsp20 is the major family of
heat shock proteins, but little of Hsp20 family is known in potato (Solanum
tuberosum), which is an important vegetable crop that is thermosensitive.
RESULTS: To reveal the mechanisms of potato Hsp20s coping with abiotic stresses,
analyses of the potato Hsp20 gene family were conducted using bioinformatics
based methods. In total, 48 putative potato Hsp20 genes (StHsp20s) were
identified and named according to their chromosomal locations. A sequence
analysis revealed that most StHsp20 genes (89.6%) possessed no, or only one,
intron. A phylogenetic analysis indicated that all of the StHsp20 genes, except
10, were grouped into 12 subfamilies. The 48 StHsp20 genes were randomly
distributed on 12 chromosomes. Nineteen tandem duplicated StHsp20s and one pair
of segmental duplicated genes (StHsp20-15 and StHsp20-48) were identified. A cis
element analysis inferred that StHsp20s, except for StHsp20-41, possessed at
least one stress response cis-element. A heatmap of the StHsp20 gene family
showed that the genes, except for StHsp20-2 and StHsp20-45, were expressed in
various tissues and organs. Real-time quantitative PCR was used to detect the
expression level of StHsp20 genes and demonstrated that the genes responded to
multiple abiotic stresses, such as heat, salt or drought stress. The relative
expression levels of 14 StHsp20 genes (StHsp20-4, 6, 7, 9, 20, 21, 33, 34, 35,
37, 41, 43, 44 and 46) were significantly up-regulated (more than 100-fold) under
heat stress. CONCLUSIONS: These results provide valuable information for
clarifying the evolutionary relationship of the StHsp20 family and in aiding
functional characterization of StHsp20 genes in further research.
PMID- 29347914
TI - In-depth proteomic analysis of boar spermatozoa through shotgun and gel-based
methods.
AB - BACKGROUND: Mature spermatozoa contain numerous epididymal and seminal plasma
proteins, which full identification through high-throughput technologies may
allow for a better understanding of the sperm biology. Therefore, we conducted a
global proteomic analysis of boar spermatozoa through shotgun and gel-based
methodologies. RESULTS: The total proteins were extracted from mature spermatozoa
and subjecsted to proteome analyses. Functional analyses of gene ontology
representations and pathway enrichments were conducted on the shotgun dataset,
followed by immunology and gene expression validations. Shotgun and gel-based
approaches allowed the detection of 2728 proteins and 2123 spots, respectively.
Approximately 38% and 59% of total proteins were respectively fully and partially
annotated, and 3% were unknown. Gene ontology analysis indicated high proportions
of proteins associated with intracellular and cytoplasm localizations, protein
and nucleic acid binding, hydrolase and transferase activities, and cellular,
metabolic, and regulation of biological processes. Proteins associated with
phosphorylation processes and mitochondrial membranes, nucleic acid binding, and
phosphate and phosphorous metabolics represented 77% of the dataset. Pathways
associated with oxidative phosphorylation, citrate cycle, and extra-cellular
matrix-receptor interaction were significantly enriched. Protein complex,
intracellular organelle, cytoskeletal parts, fertilization and reproduction, and
gap junction pathway were significantly enriched within the top 116 highly
abundant proteins. Nine randomly selected protein candidates were confirmed with
gel-based identification, immunofluorescence detection, and mRNA expression.
CONCLUSIONS: This study offers an in-depth proteomic mapping of mature boar
spermatozoa that will enable comparative and discovery research for the
improvement of male fertility.
PMID- 29347915
TI - The role of hypoglycemia in the burden of living with diabetes among adults with
diabetes and family members: results from the DAWN2 study in The Netherlands.
AB - BACKGROUND: To examine the relation between self-reported hypoglycemic events,
worries about these episodes, and the burden of diabetes in adults with diabetes
and family members from The Netherlands. METHODS: As part of the second
multinational Diabetes Attitudes, Wishes and Needs (DAWN2) study, 412 Dutch
adults with type 1 or type 2 diabetes and 86 family members completed questions
about the burden of living with diabetes, the frequency of hypoglycemia, worries
about these events, and several demographic and clinical factors. Analyses
included hierarchical logistic regression. RESULTS: In total, 41% of people with
diabetes and 56% of family members considered diabetes at least somewhat of a
burden. In people with diabetes, diabetes burden was independently associated
with self-reported current insulin use (fully adjusted OR = 2.75, 95% CI 1.49
5.10), self-reported frequent non-severe hypoglycemia in the past year (OR =
2.45, 1.25-4.83), self-reported severe hypoglycemia in the past year (OR = 1.91,
1.02-3.58), and being very worried about hypoglycemia at least occasionally (OR =
3.64, 2.18-6.10). For family members, the odds of experiencing living with
diabetes as a burden was increased only for participants who were at least
occasionally very worried about hypoglycemia (adjusted OR = 5.07, 1.12-23.00).
CONCLUSIONS: Approximately half of adults with diabetes and adult family members
experienced at least some diabetes burden. In both groups, diabetes burden
appeared to be associated with being very worried about hypoglycemia at least
occasionally. If these results are replicated, new intervention studies could
test new ways of decreasing the traumatic consequences of previous or anticipated
hypoglycemic events for people with diabetes and family members.
PMID- 29347916
TI - Cost-effectiveness of prostate cancer screening: a systematic review of decision
analytical models.
AB - BACKGROUND: There is ongoing debate about the harms and benefits of a national
prostate cancer screening programme. Several model-based cost-effectiveness
analyses have been developed to determine whether the benefits of prostate cancer
screening outweigh the costs and harms caused by over-detection and over
treatment, and the different approaches may impact results. METHODS: To identify
models of prostate cancer used to assess the cost-effectiveness of prostate
cancer screening strategies, a systematic review of articles published since 2006
was conducted using the NHS Economic Evaluation Database, Medline, EMBASE and HTA
databases. The NICE website, UK National Screening website, reference lists from
relevant studies were also searched and experts contacted. Key model features,
inputs, and cost-effectiveness recommendations were extracted. RESULTS: Ten
studies were included. Four of the studies identified some screening strategies
to be potentially cost-effective at a PSA threshold of 3.0 ng/ml, including
single screen at 55 years, annual or two yearly screens starting at 55 years old,
and delayed radical treatment. Prostate cancer screening was modelled using both
individual and cohort level models. Model pathways to reflect cancer progression
varied widely, Gleason grade was not always considered and clinical verification
was rarely outlined. Where quality of life was considered, the methods used did
not follow recommended practice and key issues of overdiagnosis and overtreatment
were not addressed by all studies. CONCLUSION: The cost-effectiveness of prostate
cancer screening is unclear. There was no consensus on the optimal model type or
approach to model prostate cancer progression. Due to limited data availability,
individual patient-level modelling is unlikely to increase the accuracy of cost
effectiveness results compared with cohort-level modelling, but is more suitable
when assessing adaptive screening strategies. Modelling prostate cancer is
challenging and the justification for the data used and the approach to modelling
natural disease progression was lacking. Country-specific data are required and
recommended methods used to incorporate quality of life. Influence of data inputs
on cost-effectiveness results need to be comprehensively assessed and the model
structure and assumptions verified by clinical experts.
PMID- 29347917
TI - Does different information disclosure on placebo control affect blinding and
trial outcomes? A case study of participant information leaflets of randomized
placebo-controlled trials of acupuncture.
AB - BACKGROUND: While full disclosure of information on placebo control in
participant information leaflets (PILs) in a clinical trial is ethically required
during informed consent, there have been concerning voices such complete
disclosures may increase unnecessary nocebo responses, breach double-blind
designs, and/or affect direction of trial outcomes. Taking an example of
acupuncture studies, we aimed to examine what participants are told about placebo
controls in randomized, placebo-controlled trials, and how it may affect blinding
and trial outcomes. METHODS: Authors of published randomized, placebo-controlled
trials of acupuncture were identified from PubMed search and invited to provide
PILs for their trials. The collected PILs were subjected to content analysis and
categorized based on degree of information disclosure on placebo. Blinding index
(BI) as a chance-corrected measurement of blinding was calculated and its
association with different information disclosure was examined. The impact of
different information disclosure from PILs on primary outcomes was estimated
using a random effects model. RESULTS: In 65 collected PILs, approximately 57% of
trials fully informed the participants of placebo control, i.e. full disclosure,
while the rest gave deceitful or no information on placebo, i.e. no disclosure.
Placebo groups in the studies with no disclosure tended to make more opposite
guesses on the type of received intervention than those with disclosure, which
may reflect wishful thinking (BI -0.21 vs. -0.16; p = 0.38). In outcome analysis,
studies with no disclosure significantly favored acupuncture than those with full
disclosure (standardized mean difference - 0.43 vs. -0.12; p = 0.03), probably
due to enhanced expectations. CONCLUSIONS: How participants are told about
placebos can be another potential factor that may influence participant blinding
and study outcomes by possibly modulating patient expectation. As we have few
empirical findings on this issue, future studies are needed to determine whether
the present findings are relevant to other medical disciplines and at the same
time a routine practice of fully disclosing placebo information in PILs calls for
reevaluation.
PMID- 29347918
TI - Somatic evolutionary timings of driver mutations.
AB - BACKGROUND: A unified analysis of DNA sequences from hundreds of tumors concluded
that the driver mutations primarily occur in the earliest stages of cancer
formation, with relatively few driver mutation events detected in the late
arising subclones. However, emerging evidence from the sequencing of multiple
tumors and tumor regions per individual suggests that late-arising subclones with
additional driver mutations are underestimated in single-sample analyses.
METHODS: To test whether driver mutations generally map to early tumor
development, we examined multi-regional tumor sequencing data from 101
individuals reported in 11 published studies. Following previous studies, we
annotated mutations as early-arising when all tumors/regions had those mutations
(ubiquitous). We then inferred the fraction of mutations occurring early and
compared it with late-arising mutations that were found in only single
tumors/regions. RESULTS: While a large fraction of driver mutations in tumors
occurred relatively early in cancers, later driver mutations occurred at least as
frequently as the early drivers in a substantial number of patients. This result
was robust to many different approaches to annotate driver mutations. The
relative frequency of early and late driver mutations varied among patients of
the same cancer type and in different cancer types. We found that previous
reports of the preponderance of early driver mutations were primarily informed by
analysis of single tumor variant allele profiles, with which it is challenging to
clearly distinguish between early and late drivers. CONCLUSIONS: The origin and
preponderance of new driver mutations are not limited to early stages of tumor
evolution, with different tumors and regions showing distinct driver mutations
and, consequently, distinct characteristics. Therefore, tumors with extensive
intratumor heterogeneity appear to have many newly acquired drivers.
PMID- 29347919
TI - Knowledge, attitudes and practices on Schistosomiasis in sub-Saharan Africa: a
systematic review.
AB - BACKGROUND: Schistosomiasis remains a global health problem with an estimated 250
million people in 78 countries infected, of whom 85% live in Sub-Saharan Africa.
Preventive chemotherapy remains the key public health strategy to combat
schistosomiasis worldwide. Recently the WHO emphasized on the use of integrative
approaches in the control and elimination of schistosomiasis. However, a detailed
understanding of sociocultural factors that may influence the uptake of the
intended health activities and services is vital. Thus, our study sought to
understand the knowledge, attitudes, perceptions, beliefs and practices about
schistosomiasis in various communities in Sub-Saharan Africa. METHODS: A
systematic search of literature for the period 2006-2016 was done on Medline,
PubMed, CINAHL, Psych info and Google Scholar using the following key words
"Schistosomiasis, S. mansoni, S. haematobium, knowledge, attitudes, perceptions,
beliefs and practices in Sub-Saharan Africa" in combination with Bolean operators
(OR, AND). In this context, we reviewed studies conducted among school children,
community members and caregivers of preschool children. Thematic analysis was
utilised for the overall synthesis of the selected studies. This was done after
reading the articles in depth. Themes were identified and examined for
similarities, differences and contradictions. RESULTS: Gaps in schistosomiasis
related knowledge and sociocultural barriers towards the uptake of preventive and
treatment services among communities in Sub-Saharan Africa were identified. In
addition to limited knowledge and negative attitudes, risky water related
practices among community members, school children and caregivers of preschool
children were identified as key factors promoting transmission of the disease.
CONCLUSION: The study concluded that a comprehensive health education programme
using contextual and standardised training tools may improve peoples' knowledge,
attitudes and practices in relation to schistosomiasis prevention and control.
Findings also highlight the significance of including caregivers in the planning
and implementation schistosomiasis control programs targeting pre-school
children.
PMID- 29347920
TI - A qualitative study of tobacco interventions for LGBTQ+ youth and young adults:
overarching themes and key learnings.
AB - BACKGROUND: Smoking prevalence is very high among lesbian, gay, bisexual,
transgendered and queer (LGBTQ+) youth and young adults (YYA) compared to non
LGBTQ+ YYA. A knowledge gap exists on culturally appropriate and effective
prevention and cessation efforts for members of this diverse community, as
limited interventions have been developed with and for this population, and there
are very few studies determining the impact of these interventions. This study
identifies the most salient elements of LGBTQ+ cessation and prevention
interventions from the perspective of LGBTQ+ YYA. METHODS: Three descriptions of
interventions tailored for LGBTQ+ YYA (group cessation counselling, social
marketing, and a mobile phone app with social media incorporated), were shared
with LGBTQ+ YYA via 24 focus groups with 204 participants in Toronto and Ottawa,
Canada. Open-ended questions focused on their feelings, likes and dislikes, and
concerns about the culturally modified intervention descriptions. Framework
analysis was used to identify overarching themes across all three intervention
descriptions. RESULTS: The data revealed eight overarching themes across all
three intervention descriptions. Smoking cessation and prevention interventions
should have the following key attributes: 1) be LGBTQ+ - specific; 2) be
accessible in terms of location, time, availability, and cost; 3) be inclusive,
relatable, and highlight diversity; 4) incorporate LGBTQ+ peer support and
counselling services; 5) integrate other activities beyond smoking; 6) be
positive, motivational, uplifting, and empowering; 7) provide concrete coping
mechanisms; and 8) integrate rewards and incentives. CONCLUSIONS: LGBTQ+ YYA
focus group participants expressed a desire for an intervention that can
incorporate these key elements. The mobile phone app and social media campaign
were noted as potential interventions that could include all the essential
elements.
PMID- 29347921
TI - Prospective pre- and post-race evaluation of biochemical, electrophysiologic, and
echocardiographic indices in 30 racing thoroughbred horses that received
furosemide.
AB - BACKGROUND: Exercise induced cardiac fatigue (EICF) and cardiac dysrhythmias are
well described conditions identified in high-level human athletes that increase
in frequency with intensity and duration of exercise. Identification of these
conditions requires an understanding of normal pre- and post-race cardiac
assessment values. The objectives of this study were to (1) characterize selected
indices of cardiac function, electrophysiologic parameters, and biochemical
markers of heart dysfunction prior to and immediately after high level racing in
Thoroughbred horses receiving furosemide; and (2) create pre- and post-race
reference values in order to make recommendations on possible screening practices
for this population in the future. RESULTS: Thirty Thoroughbred horses were
enrolled in the study with an age range of 3-6 years. All horses received
furosemide prior to racing. Physical exams, ECGs, and echocardiograms were
performed prior to racing (T0) and within 30-60 min following the race (T1).
Blood samples were obtained at T0, T1, 4 h post-race (T4) and 24 h after the race
(T24). Electrolytes, hematocrit, cardiac troponin I, and partial pressure CO2
values were obtained at all time points. Heart rate was significantly increased
post-race compared to baseline value with a median difference of 49 bpm, 95% CI
[31,58],(P < 0.0001). No dysrhythmias were noted during ECG assessment. Following
the race, an increase in number of horses demonstrating regurgitation through the
aorta and AV valves was noted. Systolic function measured by fractional
shortening increased significantly with a mean difference of 7.9%, 95% CI [4.8,
10.9], (P < 0.0001). Cardiac troponin I was not different at pre- and immediately
post-race time points, but was significantly increased at T4 (P < 0.001).
Troponin returned to baseline value by T24. CONCLUSIONS: This study utilized a
before and after study design where each horse served as its own control, as such
the possible effect of regression to the mean cannot be ruled out. The reference
intervals generated in this study may be used to identify selected
echocardiographic and electrocardiographic abnormalities in racing horses
receiving furosemide.
PMID- 29347922
TI - Characteristics of individuals receiving disability benefits in the Netherlands
and predictors of leaving the disability benefit scheme: a retrospective cohort
study with five-year follow-up.
AB - BACKGROUND: Today, work disability is one of the greatest social and labour
market challenges for policy makers in most OECD countries, where on average,
about 6% of the working-age population relies on disability benefits.
Understanding of factors associated with long-term work disability may be helpful
to identify groups of individuals at risk for disability benefit entitlement or
continuing eligibility, and to develop effective interventions for these groups.
The purpose of this study is to provide insight into the main diagnoses of
workers who qualify for disability benefits and how these diagnoses differ in
age, gender and education. Using a five-year follow-up, we examined the duration
of disability benefits and how durations differ among individuals with various
characteristics. METHODS: We performed a cohort study of 31,733 individuals
receiving disability benefits from the Dutch Social Security Institute (SSI) with
a five-year follow-up. Data were collected from SSI databases. Information about
disorders was assessed by an insurance physician upon benefit application. These
data were used to test for significant relationships among socio-demographics,
main diagnoses and comorbidity, and disability benefit entitlement and continuing
eligibility. RESULTS: Mental disorders were the most frequent diagnosis for
individuals claiming work disability. Diagnoses differed among age groups and
education categories. Mental disorders were the main diagnosis for work
disability for younger and more highly educated individuals, and physical
disorders (generally musculoskeletal, cardiovascular and cancer) were the main
diagnosis for older and less educated individuals. In 82% of the claims, the
duration of disability benefit was five years or more after approval. Outflow was
lowest for individuals with (multiple) mental disorders and those with
comorbidity of mental and physical disorders, and highest for individuals with
(multiple) physical disorders. CONCLUSIONS: The main diagnosis for persons
entitled to disability benefits was mental health problems, especially for young
women. In a five-year follow-up, claim duration for disability benefits was long
lasting for most claimants.
PMID- 29347923
TI - Endoscopic balloon dilatation for benign hepaticojejunostomy anastomotic
stricture using short double-balloon enteroscopy in patients with a prior
Whipple's procedure: a retrospective study.
AB - BACKGROUND: Endoscopic retrograde cholangiography using a short double-balloon
endoscope (DB-ERC) is a promising minimally-invasive method for accessing
hepaticojejunostomy (HJ) anastomosis in patients with surgically altered anatomy.
We aimed to evaluate the immediate and long-term outcomes of balloon dilatation
for benign HJ anastomotic stricture (HJAS) in patients who had previously
undergone Whipple's procedure using a DB-ERC. METHODS: We conducted a
retrospective analysis of 46 patients who underwent balloon dilatation alone with
a DB-ERC for benign HJAS between November 2008 and November 2014. The median
follow-up duration was 3.5 (interquartile range [IQR], 1.9-5.1) years. RESULTS:
The technical and clinical success rates were 100%, and adverse events occurred
in 7% (3/46, cholangitis). The median hospitalization period was seven (IQR, 5
10) days. Of 42 patients (91%) followed-up for > 1 year, 24 (51%) had recurrent
HJAS at a median of 1.2 (IQR, 0.6-2.9) years after balloon dilatation. The
cumulative anastomotic patency rates at 1, 2, and 3 years were 73, 55, and 49%,
respectively. In univariate analysis, early stricture formation (< 1 year) was a
risk factor for recurrent stenosis, although no statistically significant risk
factors were observed in multivariate analysis. CONCLUSIONS: Endoscopic balloon
dilatation with DB-ERC for benign HJAS is effective and safe, having good
immediate technical success and few adverse events. Further improvements to this
procedure are needed to prevent recurrent HJAS.
PMID- 29347924
TI - Causes of death in hospitalized children younger than 12 years of age in a
Chinese hospital: a 10 year study.
AB - BACKGROUND: In China, the majority (77%) of urban children die in hospitals.
Hospital-based review could provide insight leading to improvements in clinical
practice and increase the survival of critically ill children. The aim of the
present study is to identify the trends of immediate causes and chronic
underlying diseases associated with deaths of children at one of the largest
teaching hospitals in China over a period of 10 years (2006-2015). METHODS: A
retrospective analysis of data of all children aged 1 month to 11 years who died
at Xinhua Hospital between 2006 and 2015. Demographic details, main causes of
deaths, and chronic underlying diseases were reviewed. RESULTS: Case fatality
rate was 0.55% (510/93,443) and it represented 0.41-0.80% deaths per year.
Overall, the most common immediate causes of deaths in hospitalized children were
pneumonia (36.7%), sepsis (13.5%), tumour (11.4%), followed by nontraumatic
intracranial or gastrointestinal hemorrhage (10.6%) and cardiac shock (9.6%).
Over 70% of the deaths in children were complicated with chronic underlying
diseases. Congenital abnormality was the most frequent chronic underlying disease
observed in infants (60.3%) and tumour was the main chronic underlying disease in
toddlers (31.1%) and older children (44%). CONCLUSIONS: Infectious diseases,
especially pneumonia, were the major immediate causes of deaths, and the
mortality in the study population decreased with age. Tumour and other
noninfectious disease accounted for more deaths in older children. Chronic
underlying diseases were found in most deaths of children.
PMID- 29347925
TI - Alarm pheromone and kairomone detection via bitter taste receptors in the mouse
Grueneberg ganglion.
AB - BACKGROUND: The mouse Grueneberg ganglion (GG) is an olfactory subsystem
specialized in the detection of volatile heterocyclic compounds signalling
danger. The signalling pathways transducing the danger signals are only beginning
to be characterized. RESULTS: Screening chemical libraries for compounds
structurally resembling the already-identified GG ligands, we found a new
category of chemicals previously identified as bitter tastants that initiated
fear-related behaviours in mice depending on their volatility and evoked neuronal
responses in mouse GG neurons. Screening for the expression of signalling
receptors of these compounds in the mouse GG yielded transcripts of the taste
receptors Tas2r115, Tas2r131, Tas2r143 and their associated G protein alpha
gustducin (Gnat3). We were further able to confirm their expression at the
protein level. Challenging these three G protein-coupled receptors in a
heterologous system with the known GG ligands, we identified TAS2R143 as a
chemical danger receptor transducing both alarm pheromone and predator-derived
kairomone signals. CONCLUSIONS: These results demonstrate that similar molecular
elements might be used by the GG and by the taste system to detect chemical
danger signals present in the environment.
PMID- 29347926
TI - Handheld ultrasound to avert maternal and neonatal deaths in 2 regions of the
Philippines: an iBuntis(r) intervention study.
AB - BACKGROUND: The major causes of maternal and neonatal mortality in the
Philippines are hemorrhages and obstructed labor due to placental implantation
abnormalities (PIAs), twin pregnancies and fetal malpresentations. All of which
are all easily detected by ultrasound. However, women in rural areas and low
income groups do not have access to ultrasound during their prenatal care. We
aimed to provide additional evidence on the benefits of handheld ultrasound (HU)
for screening pregnancy related abnormalities in order to avert maternal and
neonatal deaths. METHODS: Using a HU, we trained community healthcare workers
(CHWs) to identify 5 obstetrical conditions: fetal viability and number,
placental localization, amniotic fluid volume (AFV) and fetal presentation.
Women, between 20th and 24th weeks age of gestation from 2 regions of the
Philippines, were scanned using the HU and the GE Logic 5 Premium ultrasound
machine for validation. Maternal and neonatal deaths averted were estimated as
health outcome measures of the study. RESULTS: Four hundred sixty women were
scanned of which 146 (31.7%) showed abnormal ultrasound readings consisting of 17
PIAs, 123 fetal malpresentation, 3 twins and 3 AFV abnormalities. The use of HU
could have possibly averted 29 (6.3%) maternal deaths and 14.6% neonatal deaths
at the time of delivery. Thirty-two out of the 460 women (~7%) delivered at home
and 93% in hospitals or birthing facilities/lying-in centers. We observed
approximately 95% agreement between the ultrasound readings of the trainees and
the trainers, and 99% agreement between the readings made from the HU with the
validation machine. CONCLUSION: CHWs could be trained in the use of HU for
scanning 5 obstetrical parameters. Early detection of abnormalities in these 5
obstetrical parameters can lead to early referral to facilities that are better
equipped to manage obstetrical emergencies. Prenatal ultrasound can be an
excellent point of care test for screening pregnant women at risk for possible
complications and even death during labor and delivery. TRIAL REGISTRATION: Thai
Clinical Trial Registry identification number TCTR20171128004 , retrospectively
registered November 28, 2017.
PMID- 29347927
TI - Prevalence of hypertensive disorders of pregnancy in Ethiopia: a systemic review
and meta-analysis.
AB - BACKGROUND: Although hypertensive disorders of pregnancy are the leading cause of
poor perinatal outcomes in Ethiopia, there is no study that shows the national
prevalence. Therefore, the aim of this study was to estimate the national pooled
prevalence of hypertensive disorders of pregnancy from studies conducted in
different parts of the country. METHODS: Databases; MEDLINE, PubMed, HINARI,
EMBASE, Google Scholar and African Journals Online were searched by using
different search terms on HDP and Ethiopia. Joanna Briggs Institute Meta-Analysis
of Statistics Assessment and Review Instrument was used for critical appraisal of
studies. The analysis was done using STATA 14 software. The Cochran Q test and I2
test statistics were used to test heterogeneity of studies. Egger's test was used
to show the publication bias. The pooled prevalence of HDP and the odds ratio
(OR) with 95% confidence interval was presented using forest plots. RESULT:
Seventeen studies were included in this review, with a total of 258,602 pregnant
women. The overall pooled prevalence of hypertensive disorders of pregnancy in
Ethiopia was 6.07% (95% CI: 4.83%, 7.31%). The Subgroup analysis by region and
year of study showed a higher prevalence of hypertensive disorders of pregnancy
in Southern Nations, Nationalities, and Peoples' Region, 10.13% (95% CI = (8.5,
12.43)), and reduction in the rate of HDP from 1990's to 2010's, 8.54% reducing
to 5.71% respectively. The pooled prevalence of pregnancy-induced hypertension
(PIH) and preeclampsia/eclampsia alone were 6.29 and 5.47 respectively. Pregnant
women >= 35 years old are more likely to develop hypertensive disorders of
pregnancy, OR = 1.64 (95% CI = (1.18, 2.28)). No statistically significant
difference was observed between HDP and younger maternal age (less than 20 years
old); OR = 2.92 (95% CI = (0.88, 9.70)). There was no association between
hypertensive disorders of pregnancy and number of pregnancy, OR = 1.37 (95% CI =
0.78, 2.41)). CONCLUSIONS: The prevalence of hypertensive disorders of pregnancy
is high in Ethiopia. The problem is more common among older pregnant women (> 35
years old). Government and other stakeholders should give due attention to an
early screening of hypertension during pregnancy.
PMID- 29347928
TI - Chronic obstructive pulmonary disease guidelines in Europe: a look into the
future.
AB - Clinical practice guidelines are ubiquitous and are developed to provide
recommendations for the management of many diseases, including chronic
obstructive pulmonary disease. The development of these guidelines is burdensome,
demanding a significant investment of time and money. In Europe, the majority of
countries develop their own national guidelines, despite the potential for
overlap or duplication of effort. A concerted effort and consolidation of
resources between countries may alleviate the resource-intensity of maintaining
individual national guidelines. Despite significant resource investment into the
development and maintenance of clinical practice guidelines, their implementation
is suboptimal. Effective strategies of guideline dissemination must be given more
consideration, to ensure adequate implementation and improved patient care
management in the future.
PMID- 29347929
TI - The HIV self-testing debate: where do we stand?
AB - BACKGROUND: Emphasis on HIV testing as a gateway to prevention, treatment and
care has grown tremendously over the past decade. In turn, this emphasis on
testing has created a demand for new policies, programs, and technologies that
can potentially increase access to and uptake of HIV testing. HIV self-testing
(HST) technologies have gained important momentum following the approval of the
over-the-counter self-tests in the United States, the UK, and France. While the
renewed interest in HST has given rise to a number of high quality reviews of
empirical studies conducted on this topic, we have yet to find an article that
captures the extent of the debate on HST. MAPPING THE DEBATE: A critical review
of the literature on HST was conducted and organized into three categories based
on the focus of the article: 1) Empirical research, 2) Arguments, and 3) Context.
We focused exclusively on the second category which included ethical analyses,
policy analyses, editorials, opinion pieces, commentaries, letters to the editor
and so forth. 10 lines of argument on HST were identified in the literature: 1)
Individual - Public Health, 2) Strengths - Limits, 3) Benefits - Harms, 4)
Screening - Testing, 5) Target - Market, 6) Health Care - Industry, 7) Regulation
- Restriction, 8) Resource-Rich Settings - Resource-Limited Settings, 9) Ethical
Unethical, and 10) Exceptionalism - Normalization. Each line of argument is
presented and discussed in the paper. CONCLUSION: We conclude by providing
examples of critical questions that should be raised in order to take the debate
to another level and generate new ways of thinking about HST.
PMID- 29347930
TI - Risk factors for stillbirths: how much can a responsive health system prevent?
AB - BACKGROUND: The stillbirth rate is an indicator of quality of care during
pregnancy and delivery. Good quality care is supported by a functional heath
system. The objective of this study was to explore the risk factors for
stillbirths, particularly those related to a health system. METHODS: This case
control study was conducted in two districts of Bihar, India. Information on
cases (stillbirths) were obtained from facilities as reported by Health
Management Information System; controls were consecutive live births from the
same population as cases. Data were collected from 400 cases and 800 controls.
The risk factors were compared using a hierarchical approach and expressed as
odds ratio, attributable fractions and population attributable fractions.
RESULTS: Of all the factors studied, 22 risk factors were independently
associated with stillbirths. Health system-related factors were: administration
of two or more doses of oxytocics to augment labour before reaching the
facilities (OR 1.6; 95% CI 1.2-2.1), any complications during labour (OR 2.3;1.7
3.1), >30 min to reach a facility from home (OR 1.4;1.05-1.8), >10 min to attend
to the pregnant woman after reaching the facility (OR 2.8;1.7-4.5). In the final
regression model, modifiable health system-related risk factors included: >10 min
taken to attend to women after they reach the facilities (AOR 3.6; 95% CI 2.5
5.1), untreated hypertension during pregnancy (AOR 2.9; 95% CI 1.5-5.6) and
presence of any complication during labour, warranting treatment (AOR 1.7; 95% CI
1.2-2.4). Among mothers who reported complications during labour, time taken to
reach the facility was significantly different between stillbirths and live
births (2nd delay; 33.5 min v/s 25 min; p < 0.001). Attributable fraction for any
complication during labour was 0.56 (95% CI 0.42-0.67), >30 min to reach the
facility 0.48 (95% CI 0.31-0.60) and institution of management 10 min after
reaching the facility 0.68 (95% CI 0.58-0.75). Reaching a facility within 30 min,
initiation of management within 10 min of reaching the facility and timely
management of complications during labour could have prevented 17%, 37% and 20%
of stillbirths respectively. CONCLUSION: A pro-active health system with
accessible, timely and quality obstetric services can prevent a considerable
proportion of stillbirths in low and middle income countries.
PMID- 29347931
TI - Attitudes towards tooth fillings in Tanzanian adults and its association with
previous filling experience.
AB - BACKGROUND: Tooth filling treatment is utilized at low levels in many low and
middle-income countries (LMICs), further, little is known about the prevailing
attitudes towards such treatment. This study aimed to assess attitudes towards
tooth filling among Tanzanian adults and how previous tooth filling experience is
associated with these attitudes. METHODS: A pretested structured questionnaire
was distributed among 1522 out-patients in four regional hospitals in Tanzania in
2015-16. The questionnaire had eight statements on a 6-point Likert scale
measuring attitudes towards tooth filling. Responses were analyzed independently
and through a constructed attitude sum score. Linear regression analysis was used
to assess the association of previous tooth fillings on attitudes towards tooth
filling treatment. RESULTS: The respondents were mostly female (57.3%), with a
mean age of 33.1 years (SD 11.3). About one third of the respondents (36.4%) had
primary level of education. Attitudes towards tooth filling treatment were
generally negative. Low levels of education and income were associated with more
negative attitudes. A small proportion (11.5%) had a previous tooth filling.
Having a previous tooth filling was associated with a more positive attitude
towards tooth fillings regardless of socioeconomic status. CONCLUSIONS: This
study shows that even in areas with limited resources and availability of
services, previous experience of tooth fillings is related to more positive
attitudes towards restorative treatment, which should be taken into account when
planning oral health care programs.
PMID- 29347932
TI - Epidemiology of arthritis, chronic back pain, gout, osteoporosis,
spondyloarthropathies and rheumatoid arthritis among 1.5 million patients in
Australian general practice: NPS MedicineWise MedicineInsight dataset.
AB - BACKGROUND: Previous estimates for the prevalence of musculoskeletal conditions
(MSK) and chronic pain in Australia have been based on self-report. We aimed to
determine the prevalence and distribution of arthritis, chronic back pain, gout,
osteoporosis, spondyloarthropathies and rheumatoid arthritis and current
consultations for chronic pain among adults attending Australian general
practice, and describe their distribution according to sociodemographic
characteristics and presence of co-morbidities. METHODS: We investigated
1,501,267 active adult patients (57.6% females; 22.5% >=65y) evaluated between
2013 and 2016 and included in the MedicineInsight database (a National
Prescribing Service MedicineWise program), a large general practice data program
that extracts longitudinal de-identified electronic medical record data from
'active' patients in over 550 practices. Three main groups of outcomes were
investigated: 1) "prevalence" of arthritis, chronic back pain, gout,
osteoporosis, spondyloarthropathies, and/or rheumatoid arthritis between 2000 and
2016; 2) "current" diagnosis/encounter for the same conditions occurring between
2013 and 2016, and; 3) "current" consultations for chronic pain of any type
occurring between 2013 and 2016. RESULTS: The combined "prevalence" of the
investigated MSK (diagnosis between 2000 and 2016) among adults attending
Australian general practice was 16.8% (95%CI 15.9;17.7) with 21.3% (95%CI
20.2;22.4) of the sample consulting for chronic pain between 2013 and 2016. The
investigated MSK with the highest "prevalence" were arthritis (9.5%) and chronic
back pain (6.7%). Patients with some of these MSK attended general practices more
frequently than those without these conditions (median 2.0 and 1.0 contacts/year,
respectively). The "prevalence" of the investigated MSK and "current"
consultations for chronic pain increased with age, especially in women, but
chronic pain remained stable at 22% for males aged > 40 years. The investigated
MSK and chronic pain were more frequent among those in lower socioeconomic
groups, veterans, Aboriginal and Torrent Strait Islanders, current and ex
smokers, and patients with chronic obstructive pulmonary disease or heart
failure. CONCLUSIONS: The investigated MSK are more frequent among lower
socioeconomic groups and the elderly. Based on information collected from adults
attending Australian general practices, MedicineInsight provided similar
estimates to those obtained from population-based studies, with the advantage of
being based on medical diagnosis and including a national sample.
PMID- 29347933
TI - A systematic review on the use of healthcare services by undocumented migrants in
Europe.
AB - BACKGROUND: Undocumented migrants face particular challenges in accessing
healthcare services in many European countries. The aim of this study was to
systematically review the academic literature on the utilization of healthcare
services by undocumented migrants in Europe. METHODS: The databases Embase,
Medline, Global Health and Cinahl Plus were searched systematically to identify
quantitative, qualitative and mixed methods studies published in 2007-2017.
RESULTS: A total of 908 articles were retrieved. Deletion of duplicates left 531.
After screening titles, abstracts and full texts according to pre-defined
inclusion and exclusion criteria, 29 articles were included in the review.
Overall, quantitative studies showed an underutilization of different types of
healthcare services by undocumented migrants. Qualitative studies reported that,
even when care was received, it was often inadequate or insufficient, and that
many undocumented migrants were unfamiliar with their entitlements and faced
barriers in utilizing healthcare services. CONCLUSIONS: Although it is difficult
to generalize findings from the included studies due to methodological
differences, they provide further evidence that undocumented migrants in Europe
face particular problems in utilizing healthcare services.
PMID- 29347934
TI - The predominant learning approaches of medical students.
PMID- 29347935
TI - Real-world experience of women using extended-cycle vs monthly-cycle combined
oral contraception in the United States: the National Health and Wellness Survey.
AB - BACKGROUND: The real-world experience of women receiving extended-cycle combined
oral contraception (COC) versus monthly-cycle COC has not been reported. METHODS:
Data were from the United States 2013 National Health and Wellness Survey.
Eligible women (18-50 years old, premenopausal, without hysterectomy) currently
using extended-cycle COC (3 months between periods) were compared with women
using monthly-cycle COC. Treatment satisfaction (1 "extremely dissatisfied" to 7
"extremely satisfied"), adherence (8-item Morisky Medication Adherence Scale(c)),
menstrual cycle-related symptoms, health-related quality of life (HRQOL) and
health state utilities (Medical Outcomes Short Form Survey-36v2(r)), depression
(9-item Patient Health Questionnaire), sleep difficulties, Work Productivity and
Activity Impairment-General Health, and healthcare resource use were assessed
using one-way analyses of variance, chi-square tests, and generalized linear
models (adjusted for covariates). RESULTS: Participants included 260 (6.7%) women
using extended-cycle and 3616 (93.3%) using monthly-cycle COC. Women using
extended-cycle COC reported significantly higher treatment satisfaction (P =
0.001) and adherence (P = 0.04) and reduced heavy menstrual bleeding (P = 0.029).
A non-significant tendency toward reduced menstrual pain (39.5% versus 47.3%) and
menstrual cycle-related symptoms (40.0% versus 48.7%) was found in women using
extended-cycle versus monthly-cycle COC. Significantly more women using extended
cycle COC reported health-related diagnoses, indicating preferential prescription
for extended-cycle COC among women reporting more health problems. Consistent
with this poorer health, more women using extended-cycle COC reported fatigue,
headache, and activity impairment (P values < 0.05). There were no other
significant differences between groups. CONCLUSIONS: This real-world
observational study supports extended-cycle COC as a valuable treatment option
with high satisfaction, high adherence, and reduced heavy menstrual bleeding.
PMID- 29347936
TI - Comparative analysis of COPD associated with tobacco smoking, biomass smoke
exposure or both.
AB - BACKGROUND: Exposure to noxious gases and particles contained in both tobacco
smoking (TS) and biomass smoke (BS) are well recognized environmental risk
factors for chronic obstructive pulmonary disease (COPD). COPD is characterized
by an abnormal inflammatory response, both in the pulmonary and systemic
compartments. The differential effects of TS, BS or their combined exposure have
not been well characterized yet. This study sought to compare the lung function
characteristics and systemic inflammatory response in COPD patients exposed to
TS, BS or their combination. METHODS: Sociodemographic, clinical and lung
functional parameters were compared across 49 COPD patients with a history of
smoking and no BS exposure (TS COPD), 31 never-smoker COPD patients with BS
exposure (BS COPD), 46 COPD patients with a combined exposure (TS + BS COPD) and
52 healthy controls (HC) who have never been exposed neither to TS or BS. Blood
cell counts, C-reactive protein (CRP), fibrinogen and immunoglobulin E (IgE)
levels were quantified in all four groups. RESULTS: TS + BS COPD patients
exhibited significantly lower oxygen saturation than the rest of groups (p <
0.01). Spirometry and diffusing capacity were significantly higher in BS than in
TS or TS + BS patients. CRP levels were significantly higher in TS COPD patients
than in BS COPD group (p < 0.05), whereas fibrinogen was raised in COPD patients
with a history of smoking (TS and TS + BS) when compared to control subjects (p <
0.01). Finally, COPD patients with BS exposure (BS and BS + TS groups) showed
higher IgE levels than TS and HC (p < 0.05). CONCLUSIONS: There are significant
physiological and inflammatory differences between COPD patients with TS, BS and
TS + BS exposures. The latter had worse blood oxygenation, whereas the raised
levels of IgE in BS exposed patients suggests a differential Th2 systemic
inflammatory pattern triggered by this pollutant.
PMID- 29347937
TI - Monoclonal antibody-based colloid gold immunochromatographic strip for the rapid
detection of Tomato zonate spot tospovirus.
AB - BACKGROUND: Tomato zonate spot virus (TZSV), a new species of genus Tospovirus,
caused significant losses in yield and problems in quality of many important
vegetables and ornamentals in Southwest China and posed a serious threat to
important economic crops for the local farmers. A convenient and reliable method
was urgently needed for rapid detection and surveillance of TZSV. METHODS: The
nucleocapsid protein (N) of TZSV was expressed in Escherichia coli and purified,
and was used as the antigen to immunize BALB/c mice. Three monoclonal antibodies
(mAbs) 3A2, 5D2 and 5F7 against TZSV were obtained through the hybridoma
technique. The mAb 3A2 was conjugated with colloid gold as detecting reagent; mAb
5D2 was coated on a porous nitrocellulose membrane as the detection line and
protein A was coated as the control line respectively. The colloid gold
immunochromatographic (GICA) strip was assembled. RESULTS: The analysis of Dot
ELISA and Western blot showed that the obtained three independent lines of mAbs
3A2, 5D2 and 5F7 specifically recognized TZSV N. Based on the assembly of GICA
strip, the detection of TZSV was achieved by loading the infected sap onto the
test strip for visual inspection. The analysis could be completed within 5-10
min. No cross-reaction occurred between TZSV and other tested viruses. The visual
detection limit of the test strip for TZSV was 800 fold dilutions of TZSV
infected leaf samples. CONCLUSION: The mAbs were specific and the colloidal GICA
strip developed in this study was convenient, fast and reliable for the detection
of TZSV. The method could be applied for the rapid diagnosis and surveillance of
TZSV in the field.
PMID- 29347938
TI - A survey of health problems of Nepalese female migrants workers in the Middle
East and Malaysia.
AB - BACKGROUND: Nepal is a key supplier of labour for countries in the Middle East,
India and Malaysia. As many more men than women leave Nepal to work abroad,
female migrant workers are a minority and very much under-researched. The aim of
the study was to explore the health problems of female Nepalese migrants working
in the Middle-East and Malaysia. METHODS: The study was conducted among 1010
women who were registered as migrant returnees at an organisation called Pourakhi
Nepal. Secondary data were extracted from the records of the organisation
covering the five-year period of July 2009 to July 2014. RESULTS: The 1010
participants were aged 14 to 51 with a median age of 31 (IQR: 38-25) years. A
quarter of respondents (24%) reported having experienced health problems while in
the country of employment. Fever, severe illness and accidents were the most
common health problems reported. Working for unlimited periods of time and not
being able to change one's place of work were independently associated with a
greater likelihood of health problems. Logistic regression shows that migrant
women who are illiterate [OR = 1.56, 95% CI: 1.02 to 2.38, p = 0.042], who had
changed their workplace [OR = 1.63, 95% CI: 1.14 to 2.32, p = 0.007], who worked
unlimited periods of time [OR = 1.64, 95% CI: 1.44 to 1.93, p = 0.020], had been
severely maltreated or tortured in the workplace [OR = 1.84, 95% CI: 1.15 to
2.92, p = 0.010], were not being paid on time [OR = 2.38, 95% CI: 1.60 to 3.55, p
= 0.038] and migrant women who had family problems at home [OR = 3.48, CI 95%:
1.22 to 9.98, p = 0.020] were significantly associated with health problems in
their host country in the Middle East. CONCLUSION: Female migrant workers face
various work-related health risks, which are often related to exploitation. The
Government of Nepal should initiate awareness campaigns about health risks and
rights in relation to health care services in the host countries. Recruiting
agencies/employers should provide information on health risks and training for
preventive measures. Raising awareness among female migrant workers can make a
change in their working lives.
PMID- 29347939
TI - Prevalence and management of severe asthma in primary care: an observational
cohort study in Sweden (PACEHR).
AB - BACKGROUND: Severe and uncontrolled asthma is associated with increased risk of
exacerbations and death. A substantial proportion of asthma patients have poor
asthma control, and a concurrent COPD diagnosis often increases disease burden.
The objective of the study was to describe the prevalence and managemant of
severe asthma in a Swedish asthma popuoation. METHODS: In this observational
cohort study, primary care medical records data (2006-2013) from 36 primary
health care centers were linked to data from national mandatory Swedish health
registries. The studied population (>18 years) had a record of drug collection
for obstructive pulmonary disease (ATC code R03) during 2011-2012, and a
physician diagnosed asthma (ICD-10 code J45-J46) prior to drug collection. Severe
asthma was classified as collection of high dose inhaled steroid (> 800
budesonide or equivalent per day) and leukotriene receptor antagonist and/or long
acting beta-agonist. Poor asthma control was defined as either collection of
>=600 doses of short-acting beta-agonists, and/or >=1 exacerbation(s) during the
year post index date. RESULTS: A total of 18,724 asthma patients (mean 49 years,
62.8% women) were included, of whom 17,934 (95.8%) had mild to moderate and 790
(4.2%) had severe asthma. Exacerbations were more prevalent in severe asthma
(2.59 [2.41-2.79], Relative Risk [95% confidence interval]; p < 0.001). Poor
asthma control was observed for 28.2% of the patients with mild to moderate
asthma and for more than half (53.6%) of the patients with severe asthma
(<0.001). Prior to index, one in five severe asthma patients had had a contact
with secondary care and one third with primary care. A concurrent COPD diagnosis
increased disease burden. CONCLUSION: Severe asthma was found in 4.2% of asthma
patients in Sweden, more than half of them had poor asthma control, and most
patients had no regular health care contacts.
PMID- 29347940
TI - Domestic feline contribution in the transmission of Sporothrix in Rio de Janeiro
State, Brazil: a comparison between infected and non-infected populations.
AB - BACKGROUND: Sporotrichosis is a neglected zoonosis caused by pathogenic fungi
belonging to the Sporothrix schenckii complex. In Rio de Janeiro state, this
disease reached an epidemic status with over 4700 domestic felines and around
4000 humans affected since the mid-90s. The present study evaluated clinical and
epidemiological aspects and also the frequency of colonization and infection by
these fungi in healthy cats and among those with suspicious cutaneous lesions,
inhabiting four Rio de Janeiro state distinct areas. RESULTS: Three hundred and
seventy-one cats were included in two groups: 175 healthy cats [CRG] and 196 cats
showing lesions suggesting sporotrichosis [SSG]. Mycological diagnosis allowed
SSG animals to be divided in positive [104 cats; +SG] and negative [92 cats; -SG]
groups. Nails, oral mucosa and lesions swabs were submitted to culture and
potential colonies were subculture for micromorphologycal analysis, dimorphism
and molecular tests. In the CRG, only one cat was colonized in the oral cavity
[0.57%]; in the -SG group, four animals showed colonization of the nail and/or
oral cavity [4.3%]; while the highest frequency of colonization [39.4%] was
observed in the +SG. All molecularly typed isolates were identified as S.
brasiliensis. CONCLUSION: The results obtained here indicate that healthy cats
have a minor role in sporotrichosis transmission within the state of Rio de
Janeiro. Conversely, a higher participation of diseased feline in sporotrichosis
transmission was evidenced, especially by the colonization of their oral cavity.
Sporothrix brasiliensis equally affects and colonizes animals from distinct Rio
de Janeiro state areas. Thus, we hypothesize that sporotrichosis is a uniform
endemic throughout the state, whose transmission depends mainly on the contact
with cats with sporotrichosis. Since Rio de Janeiro displays a world unique
epidemic model of the disease, not fully understood, data on the infected and non
infected animals can be of major importance for future strategies of
sporotrichosis prevention and control. Finally, considering the importance of the
current concept of "one health", the experience here observed can be helpful for
distinct epizootias and/or zoonosis.
PMID- 29347941
TI - A five-year retrospective study of the epidemiological characteristics and visual
outcomes of pediatric ocular trauma.
AB - BACKGROUND: Pediatric trauma can lead to serious visual impairment as a result of
the trauma itself or secondary to amblyopia. Precise data on epidemiological
characteristics and visual outcomes of pediatric ocular injuries are valuable for
the prevention of monocular blindness. METHODS: A total of 268 cases of pediatric
ocular trauma admitted to the Department of Ophthalmology of the Lithuanian
University of Health Sciences Hospital from January 2008 to December 2013 were
retrospectively reviewed. Data analysed included age, sex, cause, type and
treatment of injury, initial and final visual acuity (VA) and tissues
involvement. Eye injuries were classified by Birmingham Eye Trauma Terminology
(BETT) and Ocular Trauma Classification System (OTCS). RESULTS: The age of
children ranged from 6 months to 17.5 years. Boys were more likely to suffer
ocular injury than girls. Home was the leading place of eye injury (60.4%),
followed by outdoors (31.7%), school (5.2%) and sporting area (2.2%). The highest
percentage of eye injuries in children were caused by blunt (40.3%) and sharp
objects (29.9%), followed by burns (9.3%), falls (6.7%), explosions (4.5%),
fireworks (4.1%), gunshots (1.9%) and traffic accidents (0.7%). Closed globe
injury (CGI) was the most common type of eye injury (53.4%). CGI were noted to be
higher in children aged 13-18 years, while open globe injury (OGI) were higher in
the pre-school age group. Injury of grade 4 and grade 5 were more common in OGI,
while grade 1 and grade 2 predominated in cases of CGI. Hypotony, traumatic
cataract, iris laceration, vitreous prolapse and uveitis were the most common
presentations of OGI, while hyphema, secondary glaucoma and retinal edema were
significantly related with CGI. Final diagnoses contributing to poor final visual
outcome such as corneal scar corneal opacity, hypotony, aphakia, and retinal
detachment were statistically significant related only with OGI. Overall, 65.63%
of children regained good visual acuity (VA >= 0.5), but for 18.4% of them, the
trauma resulted in severe visual impairment (VA <= 0.1). CONCLUSION: Ocular
trauma in children still remains an important preventable cause of ocular
morbidity. This study provides data indicating that ophthalmological injuries are
a significant cause of visual impairment in children.
PMID- 29347942
TI - Infant and child mortality in relation to malaria transmission in KEMRI/CDC HDSS,
Western Kenya: validation of verbal autopsy.
AB - BACKGROUND: Malaria transmission reduction is a goal of many malaria control
programmes. Little is known of how much mortality can be reduced by specific
reductions in transmission. Verbal autopsy (VA) is widely used for estimating
malaria specific mortality rates, but does not reliably distinguish malaria from
other febrile illnesses. Overall malaria attributable mortality includes both
direct and indirect deaths. It is unclear what proportion of the deaths averted
by reducing malaria transmission are classified as malaria in VA. METHODS: Both
all-cause, and cause-specific mortality reported by VA for children under 5 years
of age, were assembled from the KEMRI/CDC health and demographic surveillance
system in Siaya county, rural Western Kenya for the years 2002-2004. These were
linked to household-specific estimates of the Plasmodium falciparum entomological
inoculation rate (EIR) based on high resolution spatio-temporal geostatistical
modelling of entomological data. All-cause and malaria specific mortality (by
VA), were analysed in relation to EIR, insecticide-treated net use (ITN),
socioeconomic status (SES) and parameters describing space-time correlation. Time
at risk for each child was analysed using Bayesian geostatistical Cox
proportional hazard models, with time-dependent covariates. The outputs were used
to estimate the diagnostic performance of VA in measuring mortality that can be
attributed to malaria exposure. RESULTS: The overall under-five mortality rate
was 80 per 1000 person-years during the study period. Eighty-one percent of the
total deaths were assigned causes of death by VA, with malaria assigned as the
main cause of death except in the neonatal period. Although no trend was observed
in malaria-specific mortality assessed by VA, ITN use was associated with reduced
all-cause mortality in infants (hazard ratio 0.15, 95% CI 0.02, 0.63) and the EIR
was strongly associated with both all-cause and malaria-specific mortality. 48.2%
of the deaths could be attributed to malaria by analysing the exposure-response
relationship, though only 20.5% of VAs assigned malaria as the cause and the
sensitivity of VAs was estimated to be only 26%. Although VAs assigned some
deaths to malaria even in areas where there was estimated to be no exposure, the
specificity of the VAs was estimated to be 85%. CONCLUSION: Interventions that
reduce P. falciparum transmission intensity will not only significantly reduce
malaria-diagnosed mortality, but also mortality assigned to other causes in under
5 year old children in endemic areas. In this setting, the VA tool based on
clinician review substantially underestimates the number of deaths that could be
averted by reducing malaria exposure in childhood, but has a reasonably high
specificity. This suggests that malaria transmission-reducing interventions such
as ITNs can potentially reduce overall child mortality by as much as twice the
total direct malaria burden estimated from VAs.
PMID- 29347943
TI - The factors that influence oral health-related quality of life in 15-year-old
children.
AB - BACKGROUND: Several hypotheses on factors that influence oral health-related
quality of life (OHRQoL) have been proposed but a consensus has not been reached.
This cross-sectional study aimed to analyse the sociodemographic and clinical
factors that may influence the OHRQoL of 15-year-old children. METHODS: A
representative sample was selected from Hong Kong. Periodontal status and caries
were examined according to WHO criteria. Four orthodontic indices were used to
assess malocclusion. Child Perception Questionnaire (CPQ11-14, 37 items)
including four domains, namely oral symptoms (OS), functional limitations (FL),
emotional well-being (EWB), and social well-being (SWB), was used to measure
OHRQoL. Adjusted OR was calculated by ordinal logistic regression. RESULTS: A
total of 364 eligible subjects (186 girls, 178 boys) were recruited. The
prevalence of caries was higher in girls than in boys (P = 0.013). Compared with
girls, boys tended to have a better experience in the domains of EWB, SWB and the
total CPQ (adjusted OR = 0.46, 0.59 and 0.61, respectively). Unhealthy
periodontal conditions were more prevalent than caries (92.6% vs. 52.7%);
moreover, periodontal conditions with CPI scores of 2 had a negative effect on
the domain of SWB and the total CPQ (adjusted OR = 1.76 and 1.71, respectively).
Only the most severe malocclusion showed an effect on the domain of FL and the
total CPQ (adjusted OR = 1.55 and 2.10, respectively). Little effect of family
ecosocial factors and caries was found on CPQ scores. CONCLUSION: In this study,
gender, periodontal status, and malocclusion showed an effect on OHRQoL after
adjusting for potential confounders. Boys had less caries and better OHRQoL than
girls did. Unhealthy periodontal conditions led to worse social welfares and
OHRQoL. The most severe level of malocclusion caused oral functional limitations,
hence worse OHRQoL.
PMID- 29347944
TI - Expression of UGP2 and CFL1 expression levels in benign and malignant pancreatic
lesions and their clinicopathological significance.
AB - BACKGROUND: This study investigated UGP2 (uridine diphosphate-glucose
pyrophosphorylase-2) and CFL1 (cofilin-1) expression in pancreatic ductal
carcinoma (PDC), paracancerous tissue (PT), benign lesions (BL), and normal
tissue (NT) and their clinicopathological significance. METHODS: Surgical
specimens, which were collected from 106 cases of pancreatic ductal carcinoma, 35
cases of paracancerous tissues, 55 cases of benign lesions and 13 cases of normal
pancreatic tissues, were fixed with 4% formaldehyde to prepare conventional
paraffin-embedded sections. EnVision immunohistochemical was used to stain for
UGP2 and CFL1. Kaplan-Meier survival analysis was performed to assess the
correlation of expression pattern with survival. RESULTS: We found that positive
UGP2 and CFL1 expression in PDC were significantly higher than those in PT, BL,
and NT. In PT and BL with positive UGP2 and CFL1 expression, mild to severe
atypical hyperplasia or intraepithelial neoplasia of grades II-III was observed
in ductal epithelium. Positive UGP2 and CFL1 expression in cases with high
differentiation, no lymph node metastasis, no surrounding invasion, and TNM
(tumor-node-metastasis) staging I or/and II were significantly lower than those
in cases with poor differentiation, lymph node metastasis, surrounding invasion,
and TNM stage III and/or IV. Positive UGP2 expression in male patients was
significantly lower than that in female patients. UGP2 and CFL1 expression in PDC
were positively correlated. Kaplan-Meier survival analysis showed the degree of
differentiation, tumor maximal diameter, TNM stage, lymph node metastasis, and
surrounding invasion, and UGP2 and CFL1 expression were closely related to the
average survival time of patients with PDC. The survival time of patients with
positive UGP2 and CFL1 expression was significantly shorter than that of patients
with negative expression. Cox multivariate analysis showed that poor
differentiation, tumor maximal diameter >= 3 cm, TNM stage III or IV, lymph node
metastasis, surrounding invasion, and positive UGP2 and CFL1 expression was
negatively correlated with the postoperative survival rate and positively
correlated with the mortality of patients with PDC. CONCLUSION: Positive
expression of UGP2 and CFL1 can serve a valuable prognostic factor in pancreatic
cancer.
PMID- 29347946
TI - Effects of long-term balance training with vibrotactile sensory augmentation
among community-dwelling healthy older adults: a randomized preliminary study.
AB - BACKGROUND: Sensory augmentation has been shown to improve postural stability
during real-time balance applications. Limited long-term controlled studies have
examined retention of balance improvements in healthy older adults after training
with sensory augmentation has ceased. This pilot study aimed to assess the
efficacy of long-term balance training with and without sensory augmentation
among community-dwelling healthy older adults. METHODS: Twelve participants (four
males, eight females; 75.6 +/- 4.9 yrs) were randomly assigned to the
experimental group (n = 6) or control group (n = 6). Participants trained in
their homes for eight weeks, completing three 45-min exercise sessions per week
using smart phone balance trainers that provided written, graphic, and video
guidance, and monitored trunk sway. During each session, participants performed
six repetitions of six exercises selected from five categories (static standing,
compliant surface standing, weight shifting, modified center of gravity, and
gait). The experimental group received vibrotactile sensory augmentation for four
of the six repetitions per exercise via the smart phone balance trainers, while
the control group performed exercises without sensory augmentation. The smart
phone balance trainers sent exercise performance data to a physical therapist,
who recommended exercises on a weekly basis. Balance performance was assessed
using a battery of clinical balance tests (Activity Balance Confidence Scale,
Sensory Organization Test, Mini Balance Evaluation Systems Test, Five Times Sit
to Stand Test, Four Square Step Test, Functional Reach Test, Gait Speed Test,
Timed Up and Go, and Timed Up and Go with Cognitive Task) before training, after
four weeks of training, and after eight weeks of training. RESULTS: Participants
in the experimental group were able to use vibrotactile sensory augmentation
independently in their homes. After training, the experimental group had
significantly greater improvements in Sensory Organization Test and Mini Balance
Evaluation Systems Test scores than the control group. Significant improvement
was also observed for Five Times Sit to Stand Test duration within the
experimental group, but not in the control group. No significant improvements
between the two groups were observed in the remaining clinical outcome measures.
CONCLUSION: The findings of this study support the use of sensory augmentation
devices by community-dwelling healthy older adults as balance rehabilitation
tools, and indicate feasibility of telerehabilitation therapy with reduced input
from clinicians.
PMID- 29347945
TI - MicroRNA transcriptome analysis of porcine vital organ responses to
immunosuppressive porcine cytomegalovirus infection.
AB - BACKGROUND: Porcine cytomegalovirus (PCMV) is an immunosuppressive virus that
mainly inhibits T-lymphocyte and macrophage immune functions; it has
significantly damaged the farming industry. Although recent studies have shown
that miRNAs play important roles in immune responses, the regulatory mechanisms
of miRNAs during immunosuppressive virus infection remain unclear. METHODS: In
this study, porcine small-RNA transcriptomes of PCMV-infected and uninfected
vital organs were first characterised by high-throughput sequencing. miRDeep2
software was used to predict novel pig-encoded miRNAs. To verify the accuracy of
the high-throughput sequencing results, stem-loop qRT-PCR was performed on 12
significantly DE miRNAs. The physical and functional interactions between the
immune-related target genes of the DE miRNAs in PCMV-infected organs were
analysed using the STRING database. RESULTS: In total, 306 annotated and 295
novel miRNAs were identified from PCMV-infected and uninfected porcine organs,
respectively, through alignment with known Sus scrofa pre-miRNAs. Overall, 92,
107, 95, 77 and 111 miRNAs were significantly differentially expressed in lung,
liver, spleen, kidney and thymus after PCMV infection, respectively. According to
Gene Ontology enrichment analysis, target genes of the differentially expressed
miRNAs associated with immune system processes, regulation of biological
processes and metabolic processes were enriched in every sample. Integrated
expression analysis of the differentially expressed miRNAs and their target mRNAs
in PCMV-infected thymus showed that the significant differential expression of
specific miRNAs under the pressure of PCMV infection in central immune organs
interfered with the expression of genes involved in important immune-related
signalling pathways, thus promoting the viral infection. CONCLUSIONS: This is the
first comprehensive analysis of the responses of host small-RNA transcriptomes to
PCMV infection in vital porcine organs. It provides new insights into the
regulatory mechanisms of miRNAs during infection by immunosuppressive viruses.
PMID- 29347947
TI - Efficacy of pre-operative quadriceps strength training on knee-extensor strength
before and shortly following total knee arthroplasty: protocol for a randomized,
dose-response trial (The QUADX-1 trial).
AB - BACKGROUND: Patients with knee osteoarthritis (OA) report knee pain, limitation
in physical activities and low quality of life. The two primary treatments for
knee OA are non-surgical treatment (e.g., exercise) and surgery (total knee
arthroplasty (TKA)); however, national guidelines recommend non-surgical
treatment to be tried prior to surgical procedures. Patients with knee OA are
characterized by decreased muscle strength, particularly in the knee-extensor
muscles. Correspondingly, decreased knee-extensor strength is found to be
associated with an increased risk of development, progression and severity of
knee OA symptoms. Recent trials suggest a positive effect of pre-operative
exercise on pre- and post-operative outcome; however, the most effective pre
operative knee-extensor strength exercise dosage is not known. The purpose of the
present trial is to investigate the efficacy of three different exercise dosages
of pre-operative, home-based, knee-extensor strength exercise on knee-extensor
strength before and shortly after surgery in patients eligible for TKA due to end
stage knee OA. METHODS: In this randomized dose-response trial with a three-arm
parallel design, 140 patients with end-stage knee OA (candidates for TKA) are
randomized to one of three exercise dosages (two, four or six session/week) of
knee-extensor strength exercise (three sets, 12 repetitions at 12 RM, per
exercise session) for 12 weeks. The knee-extensor strength exercise is home-based
(unsupervised) and performed with an elastic exercise band following an initial
exercise instruction. Adherence is objectively quantified using a sensor attached
to the exercise band. The primary outcome will be the change in knee-extensor
strength. Following the 12-week exercise period, the need for TKA surgery is re
assessed by an orthopedic surgeon. DISCUSSION: Decreased knee-extensor strength
is a major challenge in patients with knee OA. Exercise programs focusing on knee
extensor strength are found to be more effective in relieving knee OA pain and
symptoms compared to more general exercise programs. However, the optimal
exercise dosage for knee-extensor strength deficits in patients with knee OA is
inconclusive. Knowledge on the dose-response relationship for knee-extensor
strength exercise in patients with knee OA will help guide future non-surgical
treatment in this patient population. TRIAL REGISTRATION: ClinicalTrials.gov, ID:
NCT02931058 . Pre-registered on 10 October 2016.
PMID- 29347948
TI - Prenatal exposure to persistent organic pollutants and child overweight/obesity
at 5-year follow-up: a prospective cohort study.
AB - BACKGROUND: Prenatal exposure to persistent organic pollutants (POPs), may
influence offspring weight gain. More prospective epidemiological studies are
needed to compliment the growing body of evidence from animal studies. METHODS:
Serum from 412 pregnant Norwegian and Swedish women participating in a
Scandinavian prospective cohort study were collected in 1986-88, and analyses of
two perfluoroalkyl substances (PFASs) and five organochlorines (OCs) were
conducted. We used linear and logistic regression models with 95% confidence
intervals (CIs) to evaluate the associations between maternal serum POP
concentrations at 17-20 weeks of gestation and child overweight/obesity (body
mass index (BMI) >= 85th percentile) at 5-year follow-up. Results were further
stratified by country after testing for effect modification. We also assessed
potential non-monotonic dose-response (NMDR) relationships. RESULTS: In adjusted
linear models, we observed increased BMI-for-age-and-sex z-score (beta = 0.18,
95% CI: 0.01-0.35), and increased triceps skinfold z-score (beta = 0.15, 95% CI:
0.02-0.27) in children at 5-year follow-up per ln-unit increase in maternal serum
perfluorooctane sulfonate (PFOS) concentrations. We observed increased odds for
child overweight/obesity (BMI >= 85th percentile) for each ln-unit increase in
maternal serum PFOS levels (adjusted OR: 2.04, 95% CI: 1.11-3.74), with stronger
odds among Norwegian children (OR: 2.96, 95% CI: 1.42-6.15). We found similar
associations between maternal serum perfluorooctanoate (PFOA) concentrations and
child overweight/obesity. We found indications of NMDR relationships between PFOS
and polychlorinated biphenyl (PCB) 153 and child overweight/obesity among Swedish
children. CONCLUSION: We found positive associations between maternal serum PFAS
concentrations and child overweight/obesity at 5-year follow-up, particularly
among Norwegian participants. We observed some evidence for NMDR relationships
among Swedish participants.
PMID- 29347949
TI - Effects of surgery and anesthetic choice on immunosuppression and cancer
recurrence.
AB - BACKGROUND: The relationship between surgery and anesthetic-induced
immunosuppression and cancer recurrence remains unresolved. Surgery and
anesthesia stimulate the hypothalamic-pituitary-adrenal (HPA) axis and
sympathetic nervous system (SNS) to cause immunosuppression through several tumor
derived soluble factors. The potential impact of surgery and anesthesia on cancer
recurrence was reviewed to provide guidance for cancer surgical treatment.
METHODS: PubMed was searched up to December 31, 2016 using search terms such as,
"anesthetic technique and cancer recurrence," "regional anesthesia and cancer
recurrence," "local anesthesia and cancer recurrence," "anesthetic technique and
immunosuppression," and "anesthetic technique and oncologic surgery." RESULTS:
Surgery-induced stress responses and surgical manipulation enhance tumor
metastasis via release of angiogenic factors and suppression of natural killer
(NK) cells and cell-mediated immunity. Intravenous agents such as ketamine and
thiopental suppress NK cell activity, whereas propofol does not. Ketamine induces
T-lymphocyte apoptosis but midazolam does not affect cytotoxic T-lymphocytes.
Volatile anesthetics suppress NK cell activity, induce T-lymphocyte apoptosis,
and enhance angiogenesis through hypoxia inducible factor-1alpha (HIF-1alpha)
activity. Opioids suppress NK cell activity and increase regulatory T cells.
CONCLUSION: Local anesthetics such as lidocaine increase NK cell activity.
Anesthetics such as propofol and locoregional anesthesia, which decrease surgery
induced neuroendocrine responses through HPA-axis and SNS suppression, may cause
less immunosuppression and recurrence of certain types of cancer compared to
volatile anesthetics and opioids.
PMID- 29347950
TI - The microRNA-15a-PAI-2 axis in cholangiocarcinoma-associated fibroblasts promotes
migration of cancer cells.
AB - BACKGROUND: Cholangiocarcinoma (CCA) has an abundance of tumor stroma which plays
an important role in cancer progression via tumor-promoting signals. This study
aims to explore the microRNA (miRNA) profile of CCA-associated fibroblasts (CCFs)
and the roles of any identified miRNAs in CCA progression. METHODS: miRNA
expression profiles of CCFs and normal skin fibroblasts were compared by
microarray. Identified downregulated miRNAs and their target genes were confirmed
by real-time PCR. Their binding was confirmed by a luciferase reporter assay. The
effects of conditioned-media (CM) of miRNA mimic- and antagonist-transfected CCFs
were tested in CCA migration in wound healing assays. Finally, the levels of
miRNA and their target genes were examined by real-time PCR and
immunohistochemistry in clinical CCA samples. RESULTS: miR-15a was identified as
a downregulated miRNA in CCFs. Moreover, PAI-2 was identified as a novel target
gene of miR-15a. Recombinant PAI-2 promoted migration of CCA cells. Moreover, CM
from miR-15a mimic-transfected CCFs suppressed migration of CCA cells. Lower
expression of miR-15a and higher expression of PAI-2 were observed in human CCA
samples compared with normal liver tissues. Importantly, PAI-2 expression
correlated with poor prognosis in CCA patients. CONCLUSIONS: These findings
highlight the miR-15a/PAI-2 axis as a potential therapeutic target in CCA
patients.
PMID- 29347951
TI - Health-related quality of life among healthy elderly Iranians: a systematic
review and meta-analysis of the literature.
AB - BACKGROUND: Health-related quality of life (HRQoL) measurement in elderly people
can provide appropriate information for an optimal management of physical/mental
conditions. The main objective of the present study was to quantitatively assess
the HRQoL among healthy elder Iranian individuals as measured by the Short-Form
36 (SF-36) questionnaire, both overall and at the level of each its single
component/domain. METHODS: This study was designed as a systematic review and
meta-analysis, following the "Preferred Reporting Results of Systematic Reviews
and Meta-Analyses" (PRISMA) guidelines. Embase, PubMed/MEDLINE, ISI/Web of
Science (WOS), Scopus, and Iranian databases such as MagIran, SID and Irandoc
were mined from inception up to 1st September 2017. Also the grey literature (via
Google Scholar) was mined. Two reviewers independently screened titles/abstracts,
assessed full-text articles, extracted data, and appraised their quality using
the "Strengthening the Reporting of Observational Studies in Epidemiology"
(STROBE) checklist. RESULTS: Twenty five studies were included. Mean overall
HRQoL was 54.92 [95%CI 51.50-58.33], lower than the value found by studies done
in other countries, especially in those economically developed. The sensitivity
analysis indicated stability and reliability of results. Pooled scores of each
HRQoL domain/sub-scale of the SF-36 questionnaire ranged from 49.77 (physical
role functioning) to 63.02 (social role functioning). CONCLUSIONS: HRQoL among
healthy elder Iranian individuals is generally low. Health policy-makers should
put HRQoL among the elderly as a priority of their agenda, implementing ad hoc
programs and providing social, economic and psychological support, as well as
increasing the participation of old people in the community life and use their
experiences.
PMID- 29347952
TI - The German Quality Network Sepsis: study protocol for the evaluation of a quality
collaborative on decreasing sepsis-related mortality in a quasi-experimental
difference-in-differences design.
AB - BACKGROUND: While sepsis-related mortality decreased substantially in other
developed countries, mortality of severe sepsis remained as high as 44% in
Germany. A recent German cluster randomized trial was not able to improve
guideline adherence and decrease sepsis-related mortality within the
participating hospitals, partly based on lacking support by hospital management
and lacking resources for documentation of prospective data. Thus, more pragmatic
approaches are needed to improve quality of sepsis care in Germany. The primary
objective of the study is to decrease sepsis-related hospital mortality within a
quality collaborative relying on claims data. METHOD: The German Quality Network
Sepsis (GQNS) is a quality collaborative involving 75 hospitals. This study
protocol describes the conduction and evaluation of the start-up period of the
GQNS running from March 2016 to August 2018. Democratic structures assure
participatory action, a study coordination bureau provides central support and
resources, and local interdisciplinary quality improvement teams implement
changes within the participating hospitals. Quarterly quality reports focusing on
risk-adjusted hospital mortality in cases with sepsis based on claims data are
provided. Hospitals committed to publish their individual risk-adjusted mortality
compared to the German average. A complex risk-model is used to control for
differences in patient-related risk factors. Hospitals are encouraged to
implement a bundle of interventions, e.g., interdisciplinary case analyses,
external peer-reviews, hospital-wide staff education, and implementation of rapid
response teams. The effectiveness of the GQNS is evaluated in a quasi
experimental difference-in-differences design by comparing the change of hospital
mortality of cases with sepsis with organ dysfunction from a retrospective
baseline period (January 2014 to December 2015) and the intervention period
(April 2016 to March 2018) between the participating hospitals and all other
German hospitals. Structural and process quality indicators of sepsis care as
well as efforts for quality improvement are monitored regularly. DISCUSSION: The
GQNS is a large-scale quality collaborative using a pragmatic approach based on
claims data. A complex risk-adjustment model allows valid quality comparisons
between hospitals and with the German average. If this study finds the approach
to be useful for improving quality of sepsis care, it may also be applied to
other diseases. TRIAL REGISTRATION: ClinicalTrials.gov NCT02820675.
PMID- 29347953
TI - Effect of individual and community-level bed net usage on malaria prevalence
among under-fives in the Democratic Republic of Congo.
AB - BACKGROUND: Understanding the contribution of community-level long-lasting,
insecticidal net (LLIN) coverage to malaria control is critical to planning and
assessing intervention campaigns. The Democratic Republic of Congo (DRC), which
has one of the highest burdens of malaria cases and deaths and has dramatically
scaled up LLIN ownership in recent years thus it is an ideal setting to evaluate
the effect of individual versus community-level use to prevent malaria among
children under the age of 5. RESULTS: Data were derived from the 2013-2014 DRC
Demographic and Health Survey. Community-level LLIN usage was significantly
associated with protection against malaria, even when individual-level LLIN usage
was included in the model. In stratified analysis, higher levels of community
LLIN coverage enhanced the protective effect of individual LLIN usage, resulting
in lower malaria prevalence among individuals who used a LLIN. A sub-analysis of
individual LLIN usage by insecticide type revealed deltamethrin-treated nets were
more protective than permethrin-treated nets, suggesting that mosquitoes in the
DRC are more susceptible to deltamethrin. CONCLUSIONS: This study examines the
effects of individual and community-level LLIN usage in young children in an area
of high ITN usage. Individual and community LLIN usage were significantly
associated with protection against malaria in children under 5 in the DRC.
Importantly, the protective effect of individual LLIN usage against malaria is
enhanced when community LLIN coverage is higher, demonstrating the importance of
increasing community-level LLIN usage. LLINs treated with deltamethrin were shown
to be more protective against malaria than LLINs treated with permethrin.
Demographic and Health Surveys are thus a novel and important means of
surveillance for insecticide resistance.
PMID- 29347955
TI - Clinical outcomes of a combined transcatheter and minimally invasive atrial
septal defect repair program using a 'Heart Team' approach.
AB - BACKGROUND: Contemporary transcatheter and minimally invasive approaches allow
for improved cosmesis and eliminate sternotomy; however, access to a 'Heart Team'
approach to minimally invasive atrial septal defect (ASD) repair remains limited
in Canada. METHODS: Retrospective chart review of all minimally invasive atrial
septal defect repairs performed between 2009 and 2017 at a quaternary cardiac
care centre were included. We compared residual shunt, functional status,
periprocedural complications, and hospital lengths-of-stay between patients
undergoing transcatheter and minimally invasive endoscopic ASD repair. RESULTS:
Between 2009 and 2017, 61 consecutive patients underwent ASD repair at a single
centre: 28 patients underwent transcatheter closure (64.3% female; median age 57,
interquartile range 43-70.5) and 33 patients underwent minimally invasive
endoscopic repair (72.7% female; median age 37, interquartile range 24-50).
Patient demographics were similar between the two groups with the exception of
transcatheter patients having smaller defect size (1.65 cm versus 2.35 cm, p =
0.002). Procedural success was 93% (26/28) and 100% (33/33) for transcatheter and
minimally invasive groups (p = 0.21), respectively. Periprocedural complications
were similarly low between the two groups with the exception of longer hospital
length-of-stay in the surgical patients (5 days vs 1 day, p < 0.0001). Over a
follow-up period (transcatheter: 0.5-56.5 months, surgical: 0.25-89 months),
there was no difference in residual shunt (14.3% versus 6.1%, p = 0.4) or NYHA I
Functional Class (88.5% versus 96.9%, p = 0.21). CONCLUSION: Transcatheter and
minimally invasive approaches to ASD repair are safe and feasible in selected
patients using a 'Heart Team' approach and represent attractive alternatives to
median sternotomy.
PMID- 29347954
TI - A reverse vaccinology approach to the identification and characterization of
Ctenocephalides felis candidate protective antigens for the control of cat flea
infestations.
AB - BACKGROUND: Despite the abundance of the domestic cat flea, Ctenocephalides felis
(Bouche, 1835) and disease risks associated with them, flea control is difficult
and requires the development of new control interventions such as vaccines. In
this study, a reverse vaccinology approach was designed to achieve a rational
selection of cat flea candidate protective antigens. METHODS: Based on
transcriptomics and proteomics data from unfed adult fleas it was possible to
select more specific candidate protective antigens based on highly represented
and functionally relevant proteins present in the predicted exoproteome. The
protective capacity of the recombinant antigens was evaluated for the control of
C. felis infestations in vaccinated cats. RESULTS: Vaccination with recombinant
antigens induced an antibody response in immunized cats. Furthermore, a
correlation was obtained between the effect of vaccination (antibody levels) and
vaccine efficacy on flea phenotype (egg hatchability). The results suggested that
the main effect of vaccination with these antigens was on reducing cat flea egg
hatchability and fertility, with an overall vaccine efficacy of 32-46%. Although
vaccination with these antigens did not have an effect on flea infestations,
vaccines affecting reproductive capacity could reduce cat flea populations,
particularly under conditions of direct insect transmission between cats.
CONCLUSIONS: These results support the development of vaccines with protective
antigens affecting flea reproduction and development after feeding on immunized
animals for the control of cat flea infestations.
PMID- 29347956
TI - What should be included in the assessment of laypersons' paediatric basic life
support skills? Results from a Delphi consensus study.
AB - BACKGROUND: Assessment of laypersons' Paediatric Basic Life Support (PBLS) skills
is important to ensure acquisition of effective PBLS competencies. However
limited evidence exists on which PBLS skills are essential for laypersons. The
same challenges exist with respect to the assessment of foreign body airway
obstruction management (FBAOM) skills. We aimed to establish international
consensus on how to assess laypersons' PBLS and FBAOM skills. METHODS: A Delphi
consensus survey was conducted. Out of a total of 84 invited experts, 28 agreed
to participate. During the first Delphi round experts suggested items to assess
laypersons' PBLS and FBAOM skills. In the second round, the suggested items
received comments from and were rated by 26 experts (93%) on a 5-point scale (1 =
not relevant to 5 = essential). Revised items were anonymously presented in a
third round for comments and 23 (82%) experts completed a re-rating. Items with a
score above 3 by more than 80% of the experts in the third round were included in
an assessment instrument. RESULTS: In the first round, 19 and 15 items were
identified to assess PBLS and FBAOM skills, respectively. The ratings and
comments from the last two rounds resulted in nine and eight essential assessment
items for PBLS and FBAOM skills, respectively. The PBLS items included:
"Responsiveness"," Call for help", "Open airway"," Check breathing", "Rescue
breaths", "Compressions", "Ventilations", "Time factor" and "Use of AED". The
FBAOM items included: "Identify different stages of foreign body airway
obstruction", "Identify consciousness", "Call for help", "Back blows", "Chest
thrusts/abdominal thrusts according to age", "Identify loss of consciousness and
change to CPR", "Assessment of breathing" and "Ventilation". DISCUSSION: For
assessment of laypersons some PBLS and FBAOM skills described in guidelines are
more important than others. Four out of nine of PBLS skills focus on airway and
breathing skills, supporting the major importance of these skills for laypersons'
resuscitation attempts. CONCLUSIONS: International consensus on how to assess
laypersons' paediatric basic life support and foreign body airway obstruction
management skills was established. The assessment of these skills may help to
determine when laypersons have acquired competencies. TRIAL REGISTRATION: Not
relevant.
PMID- 29347957
TI - High parasite burden increases the surfacing and mortality of the manila clam
(Ruditapes philippinarum) in intertidal sandy mudflats on the west coast of Korea
during hot summer.
AB - BACKGROUND: Over the past few decades, mass mortality events of Manila clams have
been reported from several tidal flats on the west coast of Korea during hot
summers. During such mortality events, once clams simultaneously surface, they
fail to re-burrow, perishing within a week. The present study aimed to identify
the possible causes of the mass mortality of this clam species by investigating
the Perkinsus olseni parasite burden and immune parameters of surfaced clams (SC)
and normal buried clams (NBCs) when sea water or sediment temperature in the
study area varied from 25 degrees C to 34 degrees C from late July through mid
August 2015. RESULTS: We collected 2 groups of clams distributed within a 10-m2
area when a summer clam mortality event occurred around Seonyu-do Island on the
west coast of Korea in 2015. The clams were collected 2 days after they surfaced
on the sediment and still looked healthy without any gaping. The clams were
transported to the laboratory, and we compared P. olseni infection intensity and
cell-mediated hemocyte parameters between the NBCs and SCs. SCs showed
significantly higher levels of P. olseni burden, lower condition index, and lower
levels of cell-mediated immune functions than those of NBCs. CONCLUSIONS: Our
study suggests that high P. olseni infection weakens Manila clams' resistance
against thermal stress, causing them to surface. We surmise that the summer mass
mortality of Manila clams on the west coast of Korea is caused by the combined
effects of high P. olseni infection levels and abnormally high water temperature
stress.
PMID- 29347958
TI - Correlation of structural defects in the ascending aortic wall to ultrasound
parameters: benefits for decision-making process in aortic valve surgery.
AB - BACKGROUND: Histopathological changes in the ascending aorta wall in patients
with severe tricuspid aortic valve (TAV) stenosis were graded and correlated to
echocardiographic parameters. Objective was to associate threshold
echocardiographic values with structural defects in the ascending aorta providing
a tool to improve decision-making process in cases when simultaneous aortic valve
replacement (AVR) and ascending aorta replacement is considered. METHODS:
Biopsies from 108 TAV stenosis patients subjected to AVR were graded into three
grades according to severity of aortic wall changes. Echocardiographic parameters
obtained preoperatively and correlated to grade, age, gender and risk factors,
were diameters of ventriculo-aortic junction (AA), sinus Valsalva (SV),
sinotubular junction (STJ), the largest diameter of the visualized ascending
aorta (AscA) as well as indexes: sinus Valsalva (SVI), sinotubular junction
(STJI), AscA/AA and STJ/AA. RESULTS: Two echocardiographic parameters portrayed
grades with statistical significance: STJ (F = 5.417; p = 0.006 (p < 0.05)) and
AscA (F = 3.924; p = 0.023 (p < 0.05)). By using multiple predictors in the
setting of Regression analysis, statistically significant differences among
grades were reached for AA, SV, STJ, AscA and SVI. With further ROC curves
analysis, threshold values for different grades were recognized. Grade 2 is
identified in patients with AscA > 3.3 cm, while Grade 3 is identified in
patients with values of AscA > 3.5 cm, STJ > 2.9 cm and STJI > 1. CONCLUSIONS:
Hemodynamic stress induced by TAV stenosis leads to elastic lamellae disruption
in the aortic wall. Those changes could be graded and correlated with
echocardiographic parameters of the aortic root and ascending aorta, providing a
tool for decision to replace ascending aorta concomitantly with AVR.
PMID- 29347959
TI - Influence of Schistosoma japonicum programmed cell death protein 10 on the growth
and development of schistosomula.
AB - BACKGROUND: Schistosomiasis caused by Schistosoma japonicum is among the most
serious endemic zoonoses in China. To study interactions between schistosomula,
the pre-adult juvenile stage, and hosts, it is important to study the functions
of key genes involved in schistosomula growth and development. Programmed cell
death protein 10 (pcdp10) is an important apoptosis-related gene with various
biological functions. This study described the molecular characterization of S.
japonicum PCDP10 (SjPCDP10) and evaluated its functions in schistosomula.
METHODS: Real-time quantitative polymerase chain reaction (qPCR) and western blot
were used to detect Sjpcdp10 mRNA and protein levels, respectively, at different
developmental stages. Immunolocalization was performed to determine SjPCDP10
expression in the parasite. RNA interference (RNAi) experiments were used to
assess gene functions associated with SjPCDP10 in schistosomula growth and
development. RESULTS: Real-time qPCR revealed that Sjpcdp10 was expressed during
all investigated developmental stages and upregulated during schistosomula growth
and development. Histochemical localization showed that SjPCDP10 was mainly
distributed in the teguments of schistosomula in all investigated stages and part
of the parenchymal area of 14-, 18-, and 21-day-old schistosomula. Following
Sjpcdp10 knockdown by RNAi, the lengths, widths, areas, and volumes of
schistosomula were significantly lower than those in the control group. Scanning
electron microscopy showed that the body surfaces of schistosomula subjected to
RNAi were seriously damaged, with few tegumental spines and sensory papillae.
Transmission electron microscopy indicated that the teguments of Sjpcdp10
knockdown schistosomula were incomplete, the number of layers was reduced, and
the thickness decreased significantly as compared with those in the control
group. Furthermore, terminal deoxynucleotidyl transferase dUTP nick-end labelling
results showed that the rate of apoptosis in Sjpcdp10-knockdown schistosomula was
significantly higher than that in the control group. CONCLUSIONS: Sjpcdp10
knockdown influenced the growth and development of schistosomula. Therefore, our
results indicated that SjPCDP10 contributes to the regulation of cell apoptosis
and is essential for schistosomula growth and development.
PMID- 29347960
TI - Long-term outcome of definitive radiotherapy for cervical esophageal squamous
cell carcinoma.
AB - BACKGROUND: The aim of this study was to identify the long-term clinical outcome
of definitive radiotherapy using three-dimensional conformal radiotherapy (3DCRT)
for cervical esophageal squamous cell carcinoma (CESCC). METHODS: We
retrospectively reviewed the medical records of 30 patients with CESCC [clinical
stage I/II/III/IV(M1LYM); 3/2/12/13] (TNM 7th edition) who underwent definitive
radiotherapy using 3DCRT between 2000 and 2014 in our institution. The median
prescribed dose for the gross tumor and metastatic lymph nodes was 60 Gy. Twenty
six patients underwent elective nodal irradiation for the neck node levels III,
IV, and VI and for upper mediastinal lymph nodes with a median dose of 40 Gy.
Twenty-six patients underwent concurrent chemotherapy. Initial disease
progression sites, locoregional control (LRC) rate, overall survival (OS) rate,
and toxicities were retrospectively evaluated. A univariate analysis was
performed to identify prognostic factors. RESULTS: With a median follow-up of 110
months, the 5- and 10-year LRC rates were 43.7% and 37.4%, respectively. The 5-
and 10-year OS rates were 48.3% and 40.2%, respectively. Locoregional, distant
and both area accounted for 83%, 6% and 11% of the initial progression sites.
Unresectable status and M1LYM were significantly associated with poor LRC (p <
0.05) and OS (p < 0.05). Grade 3 acute non-hematological toxicity occurred in
13.3% of patients. During the follow-up, patients without any disease progression
did not need a permanent gastrostomy tube or tracheostomy. Late toxicity events,
including hypothyroidism and cardiovascular disease, were observed; 5- and 10
year cumulative incidence rates of grade 2 hypothyroidism and >=grade 3
cardiovascular disease were 31.6% and 62.5%, and 17.5% and 21.3%, respectively.
CONCLUSIONS: Definitive radiotherapy yields a cure for patients with CESCC while
preserving their laryngopharyngeal function. The poor LRC rate in the advanced
stage needs to be overcome for a better prognosis. As the incidence of radiation
induced hypothyroidism and cardiovascular disease was not low, long-term
survivors should be followed up for these symptoms.
PMID- 29347961
TI - Relevant pericardial effusion caused by cytomegalovirus infection in an
immunocompetent patient: a case report.
AB - BACKGROUND: Cytomegalovirus infection is known to cause symptomatic disease in
immunocompromised patients, while an infection in immunocompetent individuals
normally causes few or no symptoms. We present the case of an immunocompetent
adult patient with unexpected severe evolution. CASE PRESENTATION: An otherwise
healthy, 72-year-old Caucasian woman presented with complaints of progressive
shoulder pain and dyspnoea on exertion. The blood test results showed elevated
inflammation parameters and elevated hepatic transaminase levels. Radiologic
examinations were carried out, and the computed tomography scan revealed a
hepatomegaly and a chest X-ray showed evidence of a unilateral pleural effusion.
A transthoracic echocardiography detected pericardial effusion with consecutive
hemodynamic changes. Since it was considered that using ultrasound-guided
pericardiocentesis could significantly increase the risk of liver injury due to
hepatomegaly, a pericardial window was performed instead. Further investigation
showed that our patient tested positive for an acute cytomegalovirus infection in
the serologic tests. Laboratory findings included new evidence of immunoglobulin
M seroconversion and high immunoglobulin G avidity, so we considered the
possibility that a former cytomegalovirus infection may be coexisting with a new
cytomegalovirus reinfection. CONCLUSIONS: In immunocompetent individuals, a
symptomatic cytomegalovirus primary infection or reinfection should be considered
in patients presenting with pericardial effusion and serositis.
PMID- 29347962
TI - Primary explant culture and collagen I substrate enhances corneal endothelial
cell morphology.
AB - OBJECTIVES: Corneal endothelial cell (CEC) isolation and harvest aim to produce
engineered grafts to solve donor corneal tissue shortage. To yield high amounts
of CEC maintaining morphological and molecular characteristics, several isolation
and culture conditions are reported. Here, we combined direct explant culture,
with three different coating conditions and a two-step media approach to compare
confluence efficiency, morphology, and specific molecular markers expression.
DATA DESCRIPTION: Confluence was reached after 2 weeks in the three coating
conditions (Matrigel, collagen I, and in uncoated plates) using a two-step
approach (proliferative medium without pituitary extract, followed by stabilizer
basal medium). Na/K-ATPase and GPC4 markers were detected by immunocytochemistry
while GPC4, CD200, and TJP1 by RT-PCR in the three CEC coating culture
conditions. CEC in proliferative medium showed spindle morphology in the three
conditions. Polygonal morphology was seen in CEC cultures using basal medium
under uncoated and collagen I coated plates. CEC cultured in Matrigel-coated
plates remained with spindle morphology in basal medium.
PMID- 29347963
TI - Hungry to learn: the prevalence and effects of food insecurity on health
behaviors and outcomes over time among a diverse sample of university freshmen.
AB - BACKGROUND: To examine longitudinal associations between food insecurity (FI) and
health behaviors/outcomes among a diverse sample of university freshmen. METHODS:
Freshman students (n = 1138; 65% female; 49% non-white) participating in the
Social impact of Physical Activity and nutRition in College study completed
surveys on health behaviors and had height/weight measured up to 4 times (T1-T4)
in Arizona during 2015-2016. Structural equation models were estimated to
determine if, after adjusting for covariates, FI predicted concurrent
behaviors/outcomes and subsequent behaviors/outcomes. Analyses reported here were
conducted in 2017. RESULTS: The prevalence of FI was significantly higher at the
end of each semester (35% and 36%, respectively) than at the start of the year
(28%). Longitudinally, FI was not related to any health behaviors/outcomes at
future time points. However, FI was significantly and inversely associated with
concurrent breakfast consumption on most days of the week (OR = 0.67, 99% CI =
0.46, 0.99), daily evening meal consumption (OR = 0.55, 99% CI = 0.36, 0.86)
healthy eating habits on campus (OR = 0.68, 99% CI = 0.46, 1.00), healthy
physical activity habits on campus (OR = 0.66, 99% CI = 0.44, 1.00), and
positively related to the likelihood of experiencing stress (OR = 1.69, 99% CI =
1.16, 2.46) and depressed mood (OR = 1.98, 99% CI = 1.34, 2.91). CONCLUSIONS:
Compared with US prevalence rates, the sample FI prevalence was high. FI was
related to poorer eating patterns, physical activity behaviors, and mental
health, even after adjusting for prior levels of behavior.
PMID- 29347964
TI - Correction to expert consensus on re-irradiation for recurrent glioma.
AB - In the original publication [1] two author names were missing the middle names.
The corrected versions can be found in this Erratum.
PMID- 29347965
TI - Characterization of highly virulent multidrug resistant Vibrio cholerae isolated
from a large cholera outbreak in Ghana.
AB - OBJECTIVE: The purpose of this study was to investigate the virulent factors of
Vibrio cholerae which caused an unprecedented large cholera outbreak in Ghana in
2014 and progressed into 2015, affected 28,975 people with 243 deaths. RESULTS:
The V. cholerae isolates were identified to be the classical V. cholerae 01
biotype El Tor, serotype Ogawa, responsible for the large cholera outbreak in
Ghana. These El Tor strains bear CtxAB and Tcp virulent genes, making the strains
highly virulent. The strains also bear SXT transmissible element coding their
resistance to antibiotics, causing high proportions of the strains to be
multidrug resistant, with resistant proportions of 95, 90 and 75% to
trimethoprim/sulfamethoxazole, ampicillin and ceftriaxone respectively. PFGE
patterns indicated that the isolates clustered together with the same pattern and
showed clusters similar to strains circulating in DR Congo, Cameroun, Ivory Coast
and Togo. The strains carried virulence genes which facilitated the disease
causation and spread. This is the first time these virulent genes were determined
on the Ghanaian Vibrio strains.
PMID- 29347966
TI - ReprDB and panDB: minimalist databases with maximal microbial representation.
AB - BACKGROUND: Profiling of shotgun metagenomic samples is hindered by a lack of
unified microbial reference genome databases that (i) assemble genomic
information from all open access microbial genomes, (ii) have relatively small
sizes, and (iii) are compatible to various metagenomic read mapping tools.
Moreover, computational tools to rapidly compile and update such databases to
accommodate the rapid increase in new reference genomes do not exist. As a
result, database-guided analyses often fail to profile a substantial fraction of
metagenomic shotgun sequencing reads from complex microbiomes. RESULTS: We report
pipelines that efficiently traverse all open access microbial genomes and
assemble non-redundant genomic information. The pipelines result in two species
resolution microbial reference databases of relatively small sizes: reprDB, which
assembles microbial representative or reference genomes, and panDB, for which we
developed a novel iterative alignment algorithm to identify and assemble non
redundant genomic regions in multiple sequenced strains. With the databases, we
managed to assign taxonomic labels and genome positions to the majority of
metagenomic reads from human skin and gut microbiomes, demonstrating a
significant improvement over a previous database-guided analysis on the same
datasets. CONCLUSIONS: reprDB and panDB leverage the rapid increases in the
number of open access microbial genomes to more fully profile metagenomic
samples. Additionally, the databases exclude redundant sequence information to
avoid inflated storage or memory space and indexing or analyzing time. Finally,
the novel iterative alignment algorithm significantly increases efficiency in pan
genome identification and can be useful in comparative genomic analyses.
PMID- 29347967
TI - Data quality and feasibility of the Experience Sampling Method across the
spectrum of severe psychiatric disorders: a protocol for a systematic review and
meta-analysis.
AB - BACKGROUND: Due to a number of methodological advantages and theoretical
considerations, more and more studies in clinical psychology research employ the
Experience Sampling Method (ESM) as a data collection technique. Despite this
growing interest, the absence of methodological guidelines related to the use of
ESM has resulted in a large heterogeneity of designs while the potential effects
of the design itself on the response behavior of the participants remain unknown.
The objectives of this systematic review are to investigate the associations
between the design characteristics and the data quality and feasibility of
studies relying on ESM in severe psychiatric disorders. METHODS: We will search
for all published studies using ambulatory assessment with patients suffering
from major depressive disorder, bipolar disorder, and psychotic disorder or
individuals at high risk for these disorders. Electronic database searches will
be performed in PubMed and Web of Science with no restriction on the publication
date. Two reviewers will independently screen original studies in a
title/abstract phase and a full-text phase based on the inclusion criteria. The
information related to the design and sample characteristics, data quality, and
feasibility will be extracted. We will provide results in terms of a descriptive
synthesis, and when applicable, a meta-analysis of the findings will be
conducted. DISCUSSION: Our results will attempt to highlight how the feasibility
and data quality of ambulatory assessment might be related to the methodological
characteristics of the study designs in severe psychiatric disorders. We will
discuss these associations in different subsamples if sufficient data are
available and will examine limitations in the reporting of the methods of
ambulatory studies in the current literature. SYSTEMATIC REVIEW REGISTRATION: The
protocol for this systematic review was registered on PROSPERO (PROSPERO 2017:
CRD42017060322 ) and is available in full on the University of York website (
http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42017060322 ).
PMID- 29347968
TI - 18F-FDG-PET/CT and diffusion-weighted MRI for monitoring a BRAF and CDK 4/6
inhibitor combination therapy in a murine model of human melanoma.
AB - BACKGROUND: The purpose of the study was to investigate a novel BRAF and CDK 4/6
inhibitor combination therapy in a murine model of BRAF-V600-mutant human
melanoma monitored by 18F-FDG-PET/CT and diffusion-weighted MRI (DW-MRI).
METHODS: Human BRAF-V600-mutant melanoma (A375) xenograft-bearing balb/c nude
mice (n = 21) were imaged by 18F-FDG-PET/CT and DW-MRI before (day 0) and after
(day 7) a 1-week BRAF and CDK 4/6 inhibitor combination therapy (n = 12;
dabrafenib, 20 mg/kg/d; ribociclib, 100 mg/kg/d) or placebo (n = 9). Animals were
scanned on a small animal PET after intravenous administration of 20 MBq 18F-FDG.
Tumor glucose uptake was calculated as the tumor-to-liver-ratio (TTL). Unenhanced
CT data sets were subsequently acquired for anatomic coregistration. Tumor
diffusivity was assessed by DW-MRI using the apparent diffusion coefficient
(ADC). Anti-tumor therapy effects were assessed by ex vivo immunohistochemistry
for validation purposes (microvascular density - CD31; tumor cell proliferation -
Ki-67). RESULTS: Tumor glucose uptake was significantly suppressed under therapy
(?TTLTherapy - 1.00 +/- 0.53 vs. ?TTLControl 0.85 +/- 1.21; p < 0.001). In
addition, tumor diffusivity was significantly elevated following the BRAF and CDK
4/6 inhibitor combination therapy (?ADCTherapy 0.12 +/- 0.14 * 10-3 mm2/s;
?ADCControl - 0.12 +/- 0.06 * 10-3 mm2/s; p < 0.001). Immunohistochemistry
revealed a significant suppression of microvascular density (CD31, 147 +/- 48 vs.
287 +/- 92; p = 0.001) and proliferation (Ki-67, 3718 +/- 998 vs. 5389 +/- 1332;
p = 0.007) in the therapy compared to the control group. CONCLUSION: A novel BRAF
and CDK 4/6 inhibitor combination therapy exhibited significant anti-angiogenic
and anti-proliferative effects in experimental human melanomas, monitored by 18F
FDG-PET/CT and DW-MRI.
PMID- 29347969
TI - MIRO: guidelines for minimum information for the reporting of an ontology.
AB - BACKGROUND: Creation and use of ontologies has become a mainstream activity in
many disciplines, in particular, the biomedical domain. Ontology developers often
disseminate information about these ontologies in peer-reviewed ontology
description reports. There appears to be, however, a high degree of variability
in the content of these reports. Often, important details are omitted such that
it is difficult to gain a sufficient understanding of the ontology, its content
and method of creation. RESULTS: We propose the Minimum Information for Reporting
an Ontology (MIRO) guidelines as a means to facilitate a higher degree of
completeness and consistency between ontology documentation, including published
papers, and ultimately a higher standard of report quality. A draft of the MIRO
guidelines was circulated for public comment in the form of a questionnaire, and
we subsequently collected 110 responses from ontology authors, developers, users
and reviewers. We report on the feedback of this consultation, including comments
on each guideline, and present our analysis on the relative importance of each
MIRO information item. These results were used to update the MIRO guidelines,
mainly by providing more detailed operational definitions of the individual items
and assigning degrees of importance. Based on our revised version of MIRO, we
conducted a review of 15 recently published ontology description reports from
three important journals in the Semantic Web and Biomedical domain and analysed
them for compliance with the MIRO guidelines. We found that only 41.38% of the
information items were covered by the majority of the papers (and deemed
important by the survey respondents) and a large number of important items are
not covered at all, like those related to testing and versioning policies.
CONCLUSIONS: We believe that the community-reviewed MIRO guidelines can
contribute to improving significantly the quality of ontology description reports
and other documentation, in particular by increasing consistent reporting of
important ontology features that are otherwise often neglected.
PMID- 29347970
TI - A synergic effect between CYP2C19*2, CYP2C19*3 loss-of-function and CYP2C19*17
gain-of-function alleles is associated with Clopidogrel resistance among Moroccan
Acute Coronary Syndromes patients.
AB - OBJECTIVE: The main objective of our study was to investigate the association of
CYP2C19*2 and CYP2C19*3 loss-of-function and CYP2C19*17 gain-of-function variants
of CYP2C19 gene with Clopidogrel resistance in a sample of Moroccan Acute
Coronary Syndromes patients. RESULTS: Our results showed the existence of a
synergic effect between the three alleles, statistically very significant, on
Clopidogrel resistance among the treated patients (P = 0.0033). For the three
variants of the CYP2C19 gene, the heterozygous and homozygous mutant genotypes
were the most frequent among ACS patients (CYP2C19*2: 82.76% GA and 10.35% AA;
CYP2C19*3: 76.67% GA and 18.33% AA; CYP2C19*17: 66.67% CT and 18.66% TT). Allelic
frequencies were 51.73% vs 48.27% (P < 0.001); 56.67% vs 43.33% (P < 0.001); and
52% vs 48% (P = 0.01) for the mutant and wild type alleles of the CYP2C19*2,
CYP2C19*3 and CYP2C19*17 variants respectively. Our results support a role of
CYP2C19 gene variants as a potential marker of Clopidogrel response.
Understanding the functional and clinical consequences of these variants may help
for treating patients more effectively, they could be genetically screened and
appropriate dose adjustments could be made on the basis of their CYP2C19
genotype.
PMID- 29347971
TI - Detection and dissemination of Toxoplasma gondii in experimentally infected
calves, a single test does not tell the whole story.
AB - BACKGROUND: Although the detection of Toxoplasma gondii in bovine tissues is
rare, beef might be an important source of human infection. The use of molecular
techniques, such as magnetic capture qPCR (MC-qPCR), in combination with the gold
standard method for isolating the parasite (mouse bioassay), may increase the
sensitivity of T. gondii detection in infected cattle. The risk of transmission
of the parasite to humans from undercooked/raw beef is not fully known and
further knowledge about the predilection sites of T. gondii within cattle is
needed. In the current study, six Holstein Friesian calves (Bos taurus) were
experimentally infected with 106 T. gondii oocysts of the M4 strain and,
following euthanasia (42 dpi), pooled tissues were tested for presence of the
parasite by mouse bioassay and MC-qPCR. RESULTS: Toxoplasma gondii was detected
by both MC-qPCR and mouse bioassay from distinct pools (100 g) of tissues
comprising: liver, tongue, heart, diaphragm, semitendinosus (hindlimb),
longissimus dorsi muscle (sirloin) and psoas major muscle (fillet). When a
selection of individual tissues which had been used for mouse bioassay were
examined by MC-qPCR, parasite DNA could only be detected from two animals,
despite all calves showing seroconversion after infection. CONCLUSIONS: It is
apparent that one individual test will not provide an answer as to whether a calf
harbours T. gondii tissue cysts. Although the calves received a known number of
infectious oocysts and highly sensitive methods for the detection of the parasite
within bovine tissues were applied (mouse bioassay and MC-qPCR), the results
confirm previous studies which report low presence of viable T. gondii in cattle
and no clear predilection site within bovine tissues.
PMID- 29347972
TI - Extending the utility of the WHO recommended assay for direct detection of
enteroviruses from clinical specimen for resolving poliovirus co-infection.
AB - OBJECTIVES: In a polio-free world there might be reduced funding for poliovirus
surveillance. There is therefore the need to ensure that enterovirologist
globally, especially those outside the global polio laboratory network, can
participate in poliovirus surveillance without neglecting their enterovirus type
of interest. To accomplish this, assays are needed that allow such active
participation. RESULTS: In this study we describes a sensitive and specific
utility extension of the recently recommended WHO RT-snPCR assay that enables
independent detection of the three poliovirus types especially in cases of co
infection. More importantly, it piggy-backs on the first round PCR product of the
WHO recommended assay and consequently ensures that enterovirologists interested
in nonpolio enteroviruses can continue their investigations, and contribute
significantly and specifically to poliovirus surveillance, by using the excess of
their first round PCR product.
PMID- 29347973
TI - Believability of messages about preventing breast cancer and heart disease
through physical activity.
AB - BACKGROUND: The purpose of this research was to examine the relationships of self
reported physical activity to involvement with messages that discuss the
prevention of heart disease and breast cancer through physical activity, the
explicit believability of the messages, and agreement (or disagreement) with
specific statements about the messages or disease beliefs in general. METHODS: A
within subjects' design was used. Participants (N = 96) read either a breast
cancer or heart disease message first, then completed a corresponding task that
measured agreement or disagreement and confidence in the agreement or
disagreement that 1) physical activity 'reduces risk/does not reduce risk' of
breast cancer or heart disease, 2) that breast cancer or heart disease is a
'real/not real risk for me', 3) that women who get breast cancer or heart disease
are 'like/not like me', and 4) that women who get breast cancer or heart disease
are 'to blame/not to blame'. This task was followed by a questionnaire measuring
message involvement and explicit believability. They then read the other disease
messages and completed the corresponding agreement and confidence task and
questionnaire measures. Lastly, participants completed a questionnaire measuring
physical activity related attitudes and intentions, and demographics. RESULTS:
There was no difference in message involvement or explicit believability of
breast cancer compared to heart disease messages. Active participants had a
higher confidence in their agreement that physical activity is preventive of
heart disease compared to breast cancer. Multinomial regression models showed
that, in addition to physical activity related attitudes and intentions,
agreement that physical activity was preventive of heart disease and that women
with heart disease are 'like me' were predictors of being more active compared to
inactive. In the breast cancer model only attitudes and intentions predicted
physical activity group. CONCLUSIONS: Active women likely internalized messages
about heart disease prevention through physical activity, making the prevention
messages more readily available within memory, and active women may therefore
process such information differently. The study of how health-related beliefs are
created and are related to perceptions of prevention messages is a rich area of
study that may contribute to more effective health promotion.
PMID- 29347974
TI - Correction to: Sex differences in drugs: the development of a comprehensive
knowledge base to improve gender awareness prescribing.
AB - CORRECTION: Unfortunately, after publication of this article [1], two errors were
noticed. The names of Linnea Karlsson Lind and Karin Schenck-Gustafsson were
formatted incorrectly, attributing incorrect elements to the Given and Family
names. Further to this, a reference in Fig. 1 was missing. The line reading,
"Fig. 1 shows the working process and each step is explained in more detail
below" should instead read, "Fig. 1, modified from Norby et al. [2], shows the
working process and each step is explained in more detail below".
PMID- 29347976
TI - Intracisternal tuberculoma: a refractory type of tuberculoma indicating surgical
intervention.
AB - BACKGROUND: Central nervous system (CNS) tuberculoma is a rare disease with
severe neurological deficits. This retrospective research is to review the data
of patients diagnosed as CNS tuberculoma. Surgeries were performed in all
patients. The clinical features especially the neurological image and the
anatomical characters of the tuberculomas were concerned. METHODS: Totally 11
patients diagnosed as CNS tuberculoma were admitted in Guangzhou First People's
Hospital (7cases) and Changzheng Hospital (4 cases) during 2006-2015. The data
including preoperative condition, neurological imaging, and surgical findings was
collected and analyzed. RESULTS: The lesions of nine patients (9/11) were totally
or subtotally excised and two (2/11) were partially excised. Neurological
functions of all patients were improved after surgery without secondary
infection. Lesions of nine (9/11) patients preoperatively progressed as a result
of paradoxical reaction. Of the 9 patients demonstrated paradoxical progression,
all lesions were partially or totally located at the cisterns or the subarachnoid
space. Preoperative ATTs lasted 2 to 12 months and tuberculomas were not
eliminated. The arachnoid was found thickened and tightly adhered to the lesions
during surgeries. Of the 2 cases that paradoxical reaction were excluded, both
patients (case 6, intramedullary tuberculoma; case 11, intradural extramedullary
tuberculoma) were admitted at onset of the disease. ATTs were preoperatively
given for 1 week as neurological deficits aggravated. The tuberculous lesions of
CNS or other system showed no obvious change and paradoxical reaction could not
be established in both cases. CONCLUSIONS: Exudates of tuberculosis is usually
accumulated in the cisterns and frequently results in the paradoxical formation
of tuberculoma. Intracisternal tuberculoma is closely related to paradoxical
reaction and refractory to anti-tuberculosis therapy. Micro-surgical excision is
safe and effective. Early surgical intervention may be considered in the
diagnosis of intracisternal tuberculoma especially when paradoxical reaction
participates in the development of tuberculoma.
PMID- 29347977
TI - Expansion of cytochrome P450 and cathepsin genes in the generalist herbivore
brown marmorated stink bug.
AB - BACKGROUND: The brown marmorated stink bug (Halyomorpha halys) is an invasive
pest in North America which causes severe economic losses on tree fruits,
ornamentals, vegetables, and field crops. The H. halys is an extreme generalist
and this feeding behaviour may have been a major contributor behind its
establishment and successful adaptation in invasive habitats of North America. To
develop an understanding into the mechanism of H. halys' generalist herbivory,
here we specifically focused on genes putatively facilitating its adaptation on
diverse host plants. RESULTS: We generated over 142 million reads via sequencing
eight RNA-Seq libraries, each representing an individual H. halys adult. The de
novo assembly contained 79,855 high quality transcripts, totalling 39,600,178
bases. Following a comprehensive transcriptome analysis, H. halys had an expanded
suite of cytochrome P450 and cathepsin-L genes compared to other insects.
Detailed characterization of P450 genes from the CYP6 family, known for herbivore
adaptation on host plants, strongly hinted towards H. halys-specific expansions
involving gene duplications. In subsequent RT-PCR experiments, both P450 and
cathepsin genes exhibited tissue-specific or distinct expression patterns which
supported their principal roles of detoxification and/or digestion in a
particular tissue. CONCLUSIONS: Our analysis into P450 and cathepsin genes in H.
halys offers new insights into potential mechanisms for understanding generalist
herbivory and adaptation success in invasive habitats. Additionally, the large
scale transcriptomic resource developed here provides highly useful data for gene
discovery; functional, population and comparative genomics as well as efforts to
assemble and annotate the H. halys genome.
PMID- 29347975
TI - Single low-dose primaquine for blocking transmission of Plasmodium falciparum
malaria - a proposed model-derived age-based regimen for sub-Saharan Africa.
AB - BACKGROUND: In 2012, the World Health Organization recommended blocking the
transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ,
target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate
dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated
falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be
suitable for sub-Saharan Africa. METHODS: Using data on the anti-infectivity
efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and
the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant
anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0.15-0.4 mg PQ
base/kg for children aged 1-5 years and 0.15-0.5 mg PQ base/kg for individuals
aged >=6 years (therapeutic indices 2.7 and 3.3, respectively). We chose 1.25 mg
PQ base for infants aged 6-11 months because they have the highest rate of
baseline anaemia and the highest risks of AHA and CSA. We modelled an
anthropometric database of 661,979 African individuals aged >=6 months (549,127
healthy individuals, 28,466 malaria patients and 84,386 individuals with other
infections/illnesses) by the Box-Cox transformation power exponential and tested
PQ doses of 1-15 mg base, selecting dosing groups based on calculated mg/kg PQ
doses. RESULTS: From the Box-Cox transformation power exponential model, five age
categories were selected: (i) 6-11 months (n = 39,886, 6.03%), (ii) 1-5 years (n
= 261,036, 45.46%), (iii) 6-9 years (n = 20,770, 3.14%), (iv) 10-14 years (n =
12,155, 1.84%) and (v) >=15 years (n = 328,132, 49.57%) to receive 1.25, 2.5, 5,
7.5 and 15 mg PQ base for corresponding median (1st and 99th centiles) mg/kg PQ
base of: (i) 0.16 (0.12-0.25), (ii) 0.21 (0.13-0.37), (iii) 0.25 (0.16-0.38),
(iv) 0.26 (0.15-0.38) and (v) 0.27 (0.17-0.40). The proportions of individuals
predicted to receive optimal therapeutic PQ doses were: 73.2 (29,180/39,886),
93.7 (244,537/261,036), 99.6 (20,690/20,770), 99.4 (12,086/12,155) and 99.8%
(327,620/328,132), respectively. CONCLUSIONS: We plan to test the safety of this
age-based dosing regimen in a large randomised placebo-controlled trial
(ISRCTN11594437) of uncomplicated falciparum malaria in G6PDd African children
aged 0.5 - 11 years. If the regimen is safe and demonstrates adequate
pharmacokinetics, it should be used to support malaria elimination.
PMID- 29347979
TI - Altered environmental light drives retinal change in the Atlantic Tarpon
(Megalops atlanticus) over timescales relevant to marine environmental
disturbance.
AB - BACKGROUND: For many fish species, retinal function changes between life history
stages as part of an encoded developmental program. Retinal change is also known
to exhibit plasticity because retinal form and function can be influenced by
light exposure over the course of development. Aside from studies of gene
expression, it remains largely unknown whether retinal plasticity can provide
functional responses to short-term changes in environmental light quality. The
aim of this study was to determine whether the structure and function of the fish
retina can change in response to altered light intensity and spectrum-not over
the course of a developmental regime, but over shorter time periods relevant to
marine habitat disturbance. RESULTS: The effects of light environment on
sensitivity of the retina, as well as on cone photoreceptor distribution were
examined in the Atlantic tarpon (Megalops atlanticus) on 2- and 4-month
timescales. In a spectral experiment, juvenile M. atlanticus were placed in
either 'red' or 'blue' light conditions (with near identical irradiance), and in
an intensity experiment, juveniles were placed in either 'bright' or 'dim' light
conditions (with near identical spectra). Analysis of the retina by
electroretinography and anti-opsin immunofluorescence revealed that relative to
fish held in the blue condition, those in the red condition exhibited longer
wavelength peak sensitivity and greater abundance of long-wavelength-sensitive
(LWS) cone photoreceptors over time. Following pre-test dark adaption of the
retina, fish held in the dim light required less irradiance to produce a standard
retinal response than fish held in bright light, developing a greater sensitivity
to white light over time. CONCLUSIONS: The results show that structure and
function of the M. atlanticus retina can rapidly adjust to changes in
environmental light within a given developmental stage, and that such changes are
dependent on light quality and the length of exposure. These findings suggest
that the fish retina may be resilient to disturbances in environmental light,
using retinal plasticity to compensate for changes in light quality over short
timescales.
PMID- 29347978
TI - Uninvestigated dyspepsia and associated factors of patients with gastrointestinal
disorders in Dessie Referral Hospital, Northeast Ethiopia.
AB - BACKGROUND: Dyspepsia is a common problem in the community and clinical practice
with symptom(s) considered arising from the gastroduodenal region. Dyspepsia
burden and associated factors vary from country to country. The aim of this study
was to determine the prevalence of uninvestigated dyspepsia (UD) using Rome III
criteria, associated risk factors and self-reported dyspepsia symptoms'
correlation with H. pylori infection. METHODS: A cross-sectional study was
conducted among randomly selected 318 out patients with gastrointestinal
complaints during the period from September 1 to December 30, 2015. All patients
completed a questionnaire for collecting data regarding sociodemographic,
lifestyle and functional gastrointestinal disorders. Diagnosis of dyspepsia was
made according to the Rome III criteria. H. pylori infection was assessed using
stool antigen test. SPSS version 20.0 statistical software package was used for
data analysis. RESULTS: From a total of 318 patients, 48.4% had UD according to
Rome III criteria; with 42.1% symptoms of epigastric pain/burning, 26.1%
postprandial fullness and 22.6% early satiation. Epigastric pain/burning (AOR =
1.92, 95% CI 1.07-3.43), early satiation (AOR = 2.68, 95% CI 1.38-5.20) and
belching (AOR = 4.7, 95% CI 1.54-14.40) were significantly correlated with H.
pylori infection. H. pylori infection (AOR = 4.33, 95% CI 2.41-7.76) and
aspirin/NSAIDs consumption (AOR = 5.29, 95% CI 2.82-9.93) were independent risk
factors for UD. However, consumption of raw fruits/ vegetables at least once a
week (AOR = 0.48, 95% CI 0.24-0.98) and taking two or more cups of tea a day (AOR
= 0.339, 95% CI 0.17-0.70) were inversely associated with UD. CONCLUSIONS: UD is
highly prevalent among adults with gastrointestinal complaints. H. pylori
infection is significantly associated with UD and correlates with its symptoms.
Individuals with epigastric pain/burning, early satiation and belching should be
primary focus of H. pylori infection diagnosis and treatment. The role of
consumption of tea, raw fruits and vegetables on dyspepsia needs further large
scale study.
PMID- 29347980
TI - Semiprone position is superior to supine position for paediatric endotracheal
intubation during massive regurgitation, a randomized crossover simulation trial.
AB - BACKGROUND: Endotracheal intubation of patients with massive regurgitation
represents a challenge in emergency airway management. Gastric contents tend to
block suction catheters, and few treatment alternatives exist. Based on a
technique that was successfully applied in our district, we wanted to examine if
endotracheal intubation would be easier and quicker to perform when the patient
is turned over to a semiprone position, as compared to the supine position.
METHODS: In a randomized crossover simulation trial, a child manikin with on
going regurgitation was intubated both in the supine and semiprone positions.
Endpoints were experienced difficulty with the procedure and time to intubation,
as well as visually confirmed intubation and first-pass success rate. RESULTS:
Intubation in the semiprone position was significantly easier and faster compared
to the supine position; the median experienced difficulty on a visual analogue
scale was 27 and 65, respectively (p = 0.004), and the median time to intubation
was 26 and 45 s, respectively (p = 0.001). There were no significant differences
in frequency of visually confirmed intubation (16 and 18, p = 0.490) of first
pass success rate (17 and 18, p = 1.000). CONCLUSION: In this experiment,
endotracheal intubation during massive regurgitation with the patient in the
semiprone position was significantly easier and quicker to perform than in the
supine position. Endotracheal intubation in the semiprone position can provide a
quick rescue method in situations where airway management is hindered by massive
regurgitation, and it represents a possible supplement to current airway
management training.
PMID- 29347981
TI - Radiation-induced pulmonary gene expression changes are attenuated by the CTGF
antibody Pamrevlumab.
AB - BACKGROUND: Fibrosis is a delayed side effect of radiation therapy (RT).
Connective tissue growth factor (CTGF) promotes the development of fibrosis in
multiple settings, including pulmonary radiation injury. METHODS: To better
understand the cellular interactions involved in RT-induced lung injury and the
role of CTGF in these responses, microarray expression profiling was performed on
lungs of irradiated and non-irradiated mice, including mice treated with the anti
CTGF antibody pamrevlumab (FG-3019). Between group comparisons (Welch's t-tests)
and principal components analyses were performed in Genespring. RESULTS: At the
mRNA level, the ability of pamrevlumab to prolong survival and ameliorate RT
induced radiologic, histologic and functional lung deficits was correlated with
the reversal of a clear enrichment in mast cell, macrophage, dendritic cell and
mesenchymal gene signatures. Cytokine, growth factor and matrix remodeling genes
that are likely to contribute to RT pneumonitis and fibrosis were elevated by RT
and attenuated by pamrevlumab, and likely contribute to the cross-talk between
enriched cell-types in injured lung. CONCLUSIONS: CTGF inhibition had a
normalizing effect on select cell-types, including immune cells not typically
regarded as being regulated by CTGF. These results suggest that interactions
between RT-recruited cell-types are critical to maintaining the injured state;
that CTGF plays a key role in this process; and that pamrevlumab can ameliorate
RT-induced lung injury in mice and may provide therapeutic benefit in other
immune and fibrotic disorders.
PMID- 29347982
TI - Emergency department hyperoxia is associated with increased mortality in
mechanically ventilated patients: a cohort study.
AB - BACKGROUND: Providing supplemental oxygen is fundamental in the management of
mechanically ventilated patients. Increasing amounts of data show worse clinical
outcomes associated with hyperoxia. However, these previous data in the
critically ill have not focused on outcomes associated with brief hyperoxia
exposure immediately after endotracheal intubation. Therefore, the objectives of
this study were to evaluate the impact of isolated early hyperoxia exposure in
the emergency department (ED) on clinical outcomes among mechanically ventilated
patients with subsequent normoxia in the intensive care unit (ICU). METHODS: This
was an observational cohort study conducted in the ED and ICUs of an academic
center in the USA. Mechanically ventilated normoxic (partial pressure of arterial
oxygen (PaO2) 60-120 mm Hg) ICU patients with mechanical ventilation initiated in
the ED were studied. The cohort was categorized into three oxygen exposure groups
based on PaO2 values obtained after ED intubation: hypoxia, normoxia, and
hyperoxia (defined as PaO2 < 60 mmHg, PaO2 60-120 mm Hg, and PaO2 > 120 mm Hg,
respectively, based on previous literature). RESULTS: A total of 688 patients
were included. ED normoxia occurred in 350 (50.9%) patients, and 300 (43.6%) had
exposure to ED hyperoxia. The ED hyperoxia group had a median (IQR) ED PaO2 of
189 mm Hg (146-249), compared to an ED PaO2 of 88 mm Hg (76-101) in the normoxia
group, P < 0.001. Patients with ED hyperoxia had greater hospital mortality
(29.7%), when compared to those with normoxia (19.4%) and hypoxia (13.2%). After
multivariable logistic regression analysis, ED hyperoxia was an independent
predictor of hospital mortality (adjusted OR 1.95 (1.34-2.85)). CONCLUSIONS: ED
exposure to hyperoxia is common and associated with increased mortality in
mechanically ventilated patients achieving normoxia after admission. This
suggests that hyperoxia in the immediate post-intubation period could be
particularly injurious, and targeting normoxia from initiation of mechanical
ventilation may improve outcome.
PMID- 29347983
TI - Experiences of an internet-based support and coaching model for adolescents and
young adults with ADHD and autism spectrum disorder -a qualitative study.
AB - BACKGROUND: There is a great demand for non-medical treatment and support
targeting the needs of adolescents and young adults with autism spectrum disorder
(ASD) and attention-deficit/hyperactivity disorder (ADHD). There is also a lack
of qualitative studies providing in-depth insight into these individuals' own
experiences within this area. The current study aimed to explore how adolescents
and young adults with ADHD, ASD or both experienced taking part in an internet
based support and coaching intervention. METHODS: Sixteen participants with ASD,
ADHD or both who had participated in an 8-week internet-based support and
coaching model, were interviewed using semi-structured interviews. Data was
analyzed using qualitative content analysis. RESULTS: Analysis yielded three
themes; Deciding to participate, Taking part in the coaching process and The
significance of format. Various motives for joining were expressed by
participants, such as viewing the technology as familiar and appealing and
expecting it to be better suited to their situation. There was also a previously
unfulfilled need for support among participants. In deciding to take part in the
intervention the coaches' competence and knowledge were considered essential,
often in the light of previously negative experiences. Taking part in the
coaching process meant feeling reassured by having someone to turn to in view of
shared obstacles to seeking and receiving help. The support was used for talking
through and receiving advice on matters related to their diagnosis. Findings
further revealed appreciation for aspects relating to the format such as
communicating through the written word, being in one's own home and an experience
of immediacy. Some disadvantages were voiced including incomplete personal
interaction and failing technology. There were also suggestions for greater
flexibility. CONCLUSIONS: The in-depth qualitative data obtained from this study
suggest that the current model of support and the internet-based format have
specific qualities that could play an important role in the support of
adolescents and young adults with ADHD and ASD. Although not a replacement for
face-to-face interaction, it could be a promising complement or alternative to
other support and treatment options. TRIAL REGISTRATION: "Internet-based Support
for Young People with ADHD and Autism - a Controlled Study" retrospectively
registered in www.clinicaltrials.gov ( ClinicalTrials.gov Identifier: NCT02300597
) at 2014-11-10.
PMID- 29347984
TI - The effects of state rules on opioid prescribing in Indiana.
AB - BACKGROUND: Prescription opioids have been linked to over half of the 28,000
opioid overdose deaths in 2014. High rates of prescription opioid non-medical use
have continued despite nearly all states implementing large-scale prescription
drug monitoring programs (PDMP), which points to the need to examine the impact
of state PDMP's on curbing inappropriate opioid prescribing. In the short-term,
PDMPs have been associated with short-term prescribing declines. Yet little is
known about how such policies differentially impact patient subgroups or are
interpreted by prescribing providers. Our objective was to compare volumes of
prescribed opioids before and after Indiana implemented opioid prescribing
emergency rules and stratify the changes in opioid prescribing by patient and
provider subgroups. METHODS: An interrupted time series analysis was conducted
using data obtained from the Indiana PDMP. Prescription level data was merged
with census data to characterize patient socioeconomic status. Analyses were
stratified by patients' gender, age, opioid dosage, and payer. The primary
outcome indicator was the total morphine equivalent dose (MED) of dispensed
opioids per day in the state of Indiana. Also considered were number of unique
patients, unique providers, and prescriptions; MED per transaction and per day;
and number of days supplied. RESULTS: After controlling for time trends, we found
that total MED for opioids decreased after implementing the new emergency rules,
differing by patient gender, age, and payer. The effect was larger for males than
females and almost 10 times larger for 0-20 year olds as compared to the 60+ age
range. Medicare and Medicaid patients experienced more decline in prescribing
than patients with private insurance. Patients with prescriptions paid for by
workers' comp experienced the most significant decline. The emergency rules were
associated with decline in both the number of prescribers and the number of day
supply. CONCLUSIONS: Although the Indiana opioid prescribing emergency rules
impacted statewide prescribing behavior across all individual patient and
provider characteristics, the emergency rules' effect was not consistent across
patient characteristics. Further studies are needed to assess how individual
patient characteristics influence the interpretation and application of state
policies on opioid prescribing.
PMID- 29347985
TI - Seasonal and inter-annual variation of malaria parasite detection in wild
chimpanzees.
AB - BACKGROUND: Cross-sectional surveys of chimpanzee (Pan troglodytes) communities
across sub-Saharan Africa show large geographical variation in malaria parasite
(Plasmodium spp.) prevalence. The drivers leading to this apparent spatial
heterogeneity may also be temporally dynamic but data on prevalence variation
over time are missing for wild great apes. This study aims to fill this
fundamental gap. METHODS: Some 681 faecal samples were collected from 48
individuals of a group of habituated chimpanzees (Tai National Park, Cote
d'Ivoire) across four non-consecutive sampling periods between 2005 and 2015.
RESULTS: Overall, 89 samples (13%) were PCR-positive for malaria parasite DNA.
The proportion of positive samples ranged from 0 to 43% per month and 4 to 27%
per sampling period. Generalized Linear Mixed Models detected significant
seasonal and inter-annual variation, with seasonal increases during the wet
seasons and apparently stochastic inter-annual variation. Younger individuals
were also significantly more likely to test positive. CONCLUSIONS: These results
highlight strong temporal fluctuations of malaria parasite detection rates in
wild chimpanzees. They suggest that the identification of other drivers of
malaria parasite prevalence will require longitudinal approaches and caution
against purely cross-sectional studies, which may oversimplify the dynamics of
this host-parasite system.
PMID- 29347986
TI - Untapped aspects of mass media campaigns for changing health behaviour towards
non-communicable diseases in Bangladesh.
AB - In recent years, non-communicable diseases (NCDs) have become epidemic in
Bangladesh. Behaviour changing interventions are key to prevention and management
of NCDs. A great majority of people in Bangladesh have low health literacy, are
less receptive to health information, and are unlikely to embrace positive health
behaviours. Mass media campaigns can play a pivotal role in changing health
behaviours of the population. This review pinpoints the role of mass media
campaigns for NCDs and the challenges along it, whilst stressing on NCD
preventive programmes (with the examples from different countries) to change
health behaviours in Bangladesh. Future research should underpin the use of
innovative technologies and mobile phones, which might be a prospective option
for NCD prevention and management in Bangladesh.
PMID- 29347987
TI - Determinants of long-term outcome in ICU survivors: results from the FROG-ICU
study.
AB - BACKGROUND: Intensive care unit (ICU) survivors have reduced long-term survival
compared to the general population. Identifying parameters at ICU discharge that
are associated with poor long-term outcomes may prove useful in targeting an at
risk population. The main objective of the study was to identify clinical and
biological determinants of death in the year following ICU discharge. METHODS:
FROG-ICU was a prospective, observational, multicenter cohort study of ICU
survivors followed 1 year after discharge, including 21 medical, surgical or
mixed ICUs in France and Belgium. All consecutive patients admitted to intensive
care with a requirement for invasive mechanical ventilation and/or vasoactive
drug support for more than 24 h following ICU admission and discharged from ICU
were included. The main outcome measure was all-cause mortality at 1 year after
ICU discharge. Clinical and biological parameters on ICU discharge were measured,
including the circulating cardiovascular biomarkers N-terminal pro-B type
natriuretic peptide, high-sensitive troponin I, bioactive-adrenomedullin and
soluble-ST2. Socioeconomic status was assessed using a validated deprivation
index (FDep). RESULTS: Of 1570 patients discharged alive from the ICU, 333 (21%)
died over the following year. Multivariable analysis identified age, comorbidity,
red blood cell transfusion, ICU length of stay and abnormalities in common
clinical factors at the time of ICU discharge (low systolic blood pressure,
temperature, total protein, platelet and white cell count) as independent factors
associated with 1-year mortality. Elevated biomarkers of cardiac and vascular
failure independently associated with 1-year death when they are added to
multivariable model, with an almost 3-fold increase in the risk of death when
combined (adjusted odds ratio 2.84 (95% confidence interval 1.73-4.65), p <
0.001). CONCLUSIONS: The FROG-ICU study identified, at the time of ICU discharge,
potentially actionable clinical and biological factors associated with poor long
term outcome after ICU discharge. Those factors may guide discharge planning and
directed interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT01367093 .
Registered on 6 June 2011.
PMID- 29347988
TI - Efficacy of melatonin for sleep disturbance following traumatic brain injury: a
randomised controlled trial.
AB - BACKGROUND: The study aimed to determine the efficacy of melatonin
supplementation for sleep disturbances in patients with traumatic brain injury
(TBI). METHODS: This is a randomised double-blind placebo-controlled two-period
two-treatment (melatonin and placebo) crossover study. Outpatients were recruited
from Epworth and Austin Hospitals Melbourne, Australia. They had mild to severe
TBI (n = 33) reporting sleep disturbances post-injury (mean age 37 years,
standard deviation 11 years; 67% men). They were given prolonged-release
melatonin formulation (2 mg; Circadin(r)) and placebo capsules for 4 weeks each
in a counterbalanced fashion separated by a 48-hour washout period. Treatment was
taken nightly 2 hours before bedtime. Serious adverse events and side-effects
were monitored. RESULTS: Melatonin supplementation significantly reduced global
Pittsburgh Sleep Quality Index scores relative to placebo, indicating improved
sleep quality [melatonin 7.68 vs. placebo 9.47, original score units; difference
1.79; 95% confidence interval (CI), -2.70 to -0.88; p <= 0.0001]. Melatonin had
no effect on sleep onset latency (melatonin 1.37 vs. placebo 1.42, log units;
difference -0.05; 95% CI, -0.14 to 0.03; p = 0.23). With respect to the secondary
outcomes, melatonin supplementation increased sleep efficiency on actigraphy, and
vitality and mental health on the SF-36 v1 questionnaire (p <= 0.05 for each).
Melatonin decreased anxiety on the Hospital Anxiety Depression Scale and fatigue
on the Fatigue Severity Scale (p <= 0.05 for both), but had no significant effect
on daytime sleepiness on the Epworth Sleepiness Scale (p = 0.15). No serious
adverse events were reported. CONCLUSIONS: Melatonin supplementation over a 4
week period is effective and safe in improving subjective sleep quality as well
as some aspects of objective sleep quality in patients with TBI. TRIAL
REGISTRATION: Identifier: 12611000734965; Prospectively registered on 13 July
2011.
PMID- 29347989
TI - Balo's concentric sclerosis is immunologically distinct from multiple sclerosis:
results from retrospective analysis of almost 150 lumbar punctures.
AB - BACKGROUND: Balo's concentric sclerosis (BCS) is a rare inflammatory
demyelinating disorder of the central nervous system characterised by concentric
layers of demyelination. It is unclear whether BCS is a variant of multiple
sclerosis (MS) or a disease entity in its own right. OBJECTIVE: To compare the
cerebrospinal fluid (CSF) features of BCS to those of MS. METHODS: Retrospective
analysis of the CSF profile of all patients with BCS reported in the medical
literature between 1980 and 2017. RESULTS: In total, the results of 146 lumbar
punctures (LP) in 132 patients were analysed. The most striking finding was a
lack of CSF-restricted oligoclonal bands (OCB) in 66% (56/85) of all LP in the
total BCS group, in 74% (14/19) in the subgroup of patients with both MRI and
histological evidence for BCS, and in 82% (18/22) in the subgroup of patients
with highest radiological confidence (high MRI quality, >= 3 layers of
demyelination). OCB disappeared in 1/2 initially OCB-positive patients. These
findings are in stark contrast to MS, in which OCB are present in >= 95% of
patients and are thought to remain stably detectable over the entire course of
disease (p < 0.000001). OCB frequency was low both in 'historic' patients (1980
2009; 37%) and in more recent patients (2010-2017; 31%). OCB-positive and OCB
negative patients did not differ significantly with regard to age, sex, disease
duration, number of Balo-like lesions on MRI, number of relapses, treatment or
final outcome. In accordance with the high rate of OCB negativity, Link's IgG
index was negative in 63% of all tested samples (p < 0.000001 vs. MS). CSF
pleocytosis was present in 28% (27/96; p < 0.000001 vs. MS) and elevated CSF
total protein levels in 41% (31/76) of samples. CONCLUSION: OCB and IgG index
frequencies in BCS are much more similar to those reported in neuromyelitis
optica or myelin oligodendrocyte glycoprotein antibody-associated
encephalomyelitis than to those in MS. Our findings suggest that in most cases
BCS-like lesions denote the presence of a disease entity immunologically distinct
from MS. In addition, we provide data on the demographics, clinical course and
radiological features of BCS based on the largest cohort analysed to date.
PMID- 29347990
TI - Establishment of an in vitro chicken epithelial cell line model to investigate
Eimeria tenella gamete development.
AB - BACKGROUND: Eimeria tenella infection leads to acute intestinal disorders
responsible for important economic losses in poultry farming worldwide. The life
cycle of E. tenella is monoxenous with the chicken as the exclusive host;
infection occurs in caecal epithelial cells. However, in vitro, the complete life
cycle of the parasite has only been propagated successfully in primary chicken
kidney cells, which comprise undefined mixed cell populations; no cell line model
has been able to consistently support the development of the sexual stages of the
parasite. We therefore sought to develop a new model to study E. tenella
gametogony in vitro using a recently characterised chicken cell line (CLEC-213)
exhibiting an epithelial cell phenotype. METHODS: CLEC-213 were infected with
sporozoites from a precocious strain or with second generation merozoites
(merozoites II) from wild type strains. Sexual stages of the parasite were
determined both at the gene and protein levels. RESULTS: To our knowledge, we
show for the first time in CLEC-213, that sporozoites from a precocious strain of
E. tenella were able to develop to gametes, as verified by measuring gene
expression and by using antibodies to a microgamete-specific protein (EtFOA1:
flagellar outer arm protein 1) and a macrogamete-specific protein (EtGAM-56), but
oocysts were not observed. However, both gametes and oocysts were observed when
cells were infected with merozoites II from wild type strains, demonstrating that
completion of the final steps of the parasite cycle is possible in CLEC-213
cells. CONCLUSION: The epithelial cell line CLEC-213 constitutes a useful avian
tool for studying Eimeria epithelial cell interactions and the effect of drugs on
E. tenella invasion, merogony and gametogony.
PMID- 29347992
TI - Anatomical relation between S1 sacroiliac screws' entrance points and superior
gluteal artery.
AB - BACKGROUND: To conduct radiologic anatomical study on the relation between S1
sacroiliac screws' entry points and the route of the pelvic outer superior
gluteal artery branches with the aim to provide the anatomical basis and
technical reference for the avoidance of damage to the superior gluteal artery
during the horizontal sacroiliac screw placement. METHODS: Superior gluteal
artery CTA (CT angiography) vascular imaging of 74 healthy adults (37 women and
37 men) was done with 128-slice spiral CT (computed tomography). The CT attendant
measuring software was used to portray the "safe bony entrance area" (hereinafter
referred to as "Safe Area") of the S1 segment in the standard lateral pelvic view
of three-dimensional reconstruction. The anatomical relation between S1
sacroiliac screws' Safe Area and the pelvic outer superior gluteal artery
branches was observed and recorded. The number of cases in which artery branches
intersected the Safe Area was counted. The cases in which superior gluteal artery
branches disjointed from the Safe Area were identified, and the shortest distance
between the Safe Area and the superior gluteal artery branch closest to the Safe
Area was measured. RESULTS: Three cases out of the 74 sample cases were excluded
from this study as they were found to have no bony space for horizontal screw
placement in S1 segment. Among the remaining 71 sample cases, there are 32 cases
(45.1%) where the deep superior branch of superior gluteal artery passes through
the Safe Area of S1 entrance point. There was no distinguishing feature and rule
on how the deep superior branches and the Safe Area overlapped. In the 39 cases
in which superior gluteal artery branches disjointed from the Safe Area, the deep
superior branches of superior gluteal artery were the branches closest to the
Safe Area and the part of the branch closest to the Safe Area was located in
front of the widest part of the Safe Area. The shortest distance between the deep
superior branch and the Safe Area is 0.86 +/- 0.84 cm. CONCLUSION: There is a
high risk of accidental injury of the deep superior branches of superior gluteal
artery in the process of S1 sacroiliac screw placement. Even if the entry points
are located in the safe bony entrance area, the absolute secure placement cannot
be assured. We suggest that great attention should be paid to make thorough
preoperative plans.
PMID- 29347991
TI - The benefits and tolerance of exercise in myasthenia gravis (MGEX): study
protocol for a randomised controlled trial.
AB - BACKGROUND: Research exploring the effects of physical exercise in auto-immune
myasthenia gravis (MG) is scarce. The few existing studies present methodological
shortcomings limiting the conclusions and generalisability of results. It is
hypothesised that exercise could have positive physical, psychological as well as
immunomodulatory effects and may be a beneficial addition to current
pharmacological management of this chronic disease. The aim of this study is to
evaluate the benefits on perceived quality of life (QOL) and physical fitness of
a home-based physical exercise program compared to usual care, for patients with
stabilised, generalised auto-immune MG. METHODS: MGEX is a multi-centre,
interventional, randomised, single-blind, two-arm parallel group, controlled
trial. Forty-two patients will be recruited, aged 18-70 years. Following a three
month observation period, patients will be randomised into a control or
experimental group. The experimental group will undertake a 40-min home-based
physical exercise program using a rowing machine, three times a week for three
months, as an add-on to usual care. The control group will receive usual care
with no additional treatment. All patients will be followed up for a further
three months. The primary outcome is the mean change in MGQOL-15-F score between
three and six months (i.e. pre-intervention and immediately post-intervention
periods). The MGQOL-15-F is an MG-specific patient-reported QOL questionnaire.
Secondary outcomes include the evaluation of deficits and functional limitations
via MG-specific clinical scores (Myasthenia Muscle Score and MG-Activities of
Daily Living scale), muscle force and fatigue, respiratory function, free-living
physical activity as well as evaluations of anxiety, depression, self-esteem and
overall QOL with the WHO-QOL BREF questionnaire. Exercise workload will be
assessed as well as multiple safety measures (ECG, biological markers, medication
type and dosage and any disease exacerbation or crisis). DISCUSSION: This is the
largest randomised controlled trial to date evaluating the benefits and tolerance
of physical exercise in this patient population. The comprehensive evaluations
using standardised outcome measures should provide much awaited information for
both patients and the scientific community. This study is ongoing. TRIAL
REGISTRATION: ClinicalTrials.gov, NCT02066519 . Registered on 13 January 2014.
PMID- 29347993
TI - Updated efficacy of avelumab in patients with previously treated metastatic
Merkel cell carcinoma after >=1 year of follow-up: JAVELIN Merkel 200, a phase 2
clinical trial.
AB - BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer
associated with poor survival outcomes in patients with distant metastatic
disease (mMCC). In an initial analysis from JAVELIN Merkel 200, a phase 2,
prospective, open-label, single-arm trial in mMCC, avelumab-a human anti
programmed death-ligand 1 (PD-L1) monoclonal antibody-showed promising efficacy
and a safety profile that was generally manageable and tolerable. Here, we report
the efficacy of avelumab after >=1 year of follow-up in patients with distant
mMCC that had progressed following prior chemotherapy for metastatic disease.
PATIENTS AND METHODS: Patients received avelumab 10 mg/kg by 1-h intravenous
infusion every 2 weeks until confirmed disease progression, unacceptable
toxicity, or withdrawal. The primary endpoint was best overall response.
Secondary endpoints included duration of response (DOR), progression-free
survival (PFS), and overall survival (OS). RESULTS: Patients (N = 88) were
followed for a minimum of 12 months. The confirmed objective response rate was
33.0% (95% CI, 23.3%-43.8%; complete response: 11.4%). An estimated 74% of
responses lasted >=1 year, and 72.4% of responses were ongoing at data cutoff.
Responses were durable, with the median DOR not yet reached (95% CI, 18.0 months
not estimable), and PFS was prolonged; 1-year PFS and OS rates were 30% (95% CI,
21%-41%) and 52% (95% CI, 41%-62%), respectively. Median OS was 12.9 months (95%
CI, 7.5-not estimable). Subgroup analyses suggested a higher probability of
response in patients receiving fewer prior lines of systemic therapy, with a
lower baseline disease burden, and with PD-L1-positive tumors; however, durable
responses occurred irrespective of baseline factors, including tumor Merkel cell
polyomavirus status. CONCLUSIONS: With longer follow-up, avelumab continues to
show durable responses and promising survival outcomes in patients with distant
mMCC whose disease had progressed after chemotherapy. TRIAL REGISTRATION:
Clinicaltrials.gov identifier: NCT02155647.
PMID- 29347995
TI - Index of the human papillomavirus (HPV) vaccine industry clinical study
programmes and non-industry funded studies: a necessary basis to address
reporting bias in a systematic review.
AB - BACKGROUND: Unabridged access to drug industry and regulatory trial registers and
data reduces reporting bias in systematic reviews and may provide a complete
index of a drug's clinical study programme. Currently, there is no public index
of the human papillomavirus (HPV) vaccine industry study programmes or a public
index of non-industry funded studies. METHODS: By cross-verification via study
programme enquiries to the HPV vaccine manufacturers and regulators and searches
of trial registers and journal publication databases, we indexed clinical HPV
vaccine studies as a basis to address reporting bias in a systematic review of
clinical study reports. RESULTS: We indexed 206 clinical studies: 145 industry
and 61 non-industry funded studies. One of the four HPV vaccine manufacturers
(GlaxoSmithKline) provided information on its study programme. Most studies were
cross-verified from two or more sources (160/206, 78%) and listed on regulatory
or industry trial registers or journal publication databases (195/206, 95%)-in
particular, on ClinicalTrials.gov (176/195, 90%). However, study results were
only posted for about half of the completed studies on ClinicalTrials.gov
(71/147, 48%). Two thirds of the industry studies had a study programme ID,
manufacturer specific ID, and national clinical trial (NCT) ID (91/145, 63%).
Journal publications were available in journal publication databases (the
Cochrane Collaboration's Central Register of Controlled Trials, Google Scholar
and PubMed) for two thirds of the completed studies (92/149, 62%). CONCLUSION: We
believe we came close to indexing complete HPV vaccine study programmes, but only
one of the four manufacturers provided information for our index and a fifth of
the index could not be cross-verified. However, we indexed larger study
programmes than those listed by major regulators (i.e., the EMA and FDA that
based their HPV vaccine approvals on only half of the available trials). To
reduce reporting bias in systematic reviews, we advocate the registration and
publication of all studies and data in the public domain.
PMID- 29347994
TI - The apelinergic system as an alternative to catecholamines in low-output septic
shock.
AB - Catecholamines, in concert with fluid resuscitation, have long been recommended
in the management of septic shock. However, not all patients respond positively
and controversy surrounding the efficacy-to-safety profile of catecholamines has
emerged, trending toward decatecholaminization. Contextually, it is time to re
examine the "maintaining blood pressure" paradigm by identifying safer and life
saving alternatives. We put in perspective the emerging and growing knowledge on
a promising alternative avenue: the apelinergic system. This target exhibits
invaluable pleiotropic properties, including inodilator activity, cardio-renal
protection, and control of fluid homeostasis. Taken together, its effects are
expected to be greatly beneficial for patients in septic shock.
PMID- 29347997
TI - OpenBiodiv-O: ontology of the OpenBiodiv knowledge management system.
AB - BACKGROUND: The biodiversity domain, and in particular biological taxonomy, is
moving in the direction of semantization of its research outputs. The present
work introduces OpenBiodiv-O, the ontology that serves as the basis of the
OpenBiodiv Knowledge Management System. Our intent is to provide an ontology that
fills the gaps between ontologies for biodiversity resources, such as DarwinCore
based ontologies, and semantic publishing ontologies, such as the SPAR
Ontologies. We bridge this gap by providing an ontology focusing on biological
taxonomy. RESULTS: OpenBiodiv-O introduces classes, properties, and axioms in the
domains of scholarly biodiversity publishing and biological taxonomy and aligns
them with several important domain ontologies (FaBiO, DoCO, DwC, Darwin-SW,
NOMEN, ENVO). By doing so, it bridges the ontological gap across scholarly
biodiversity publishing and biological taxonomy and allows for the creation of a
Linked Open Dataset (LOD) of biodiversity information (a biodiversity knowledge
graph) and enables the creation of the OpenBiodiv Knowledge Management System. A
key feature of the ontology is that it is an ontology of the scientific process
of biological taxonomy and not of any particular state of knowledge. This feature
allows it to express a multiplicity of scientific opinions. The resulting
OpenBiodiv knowledge system may gain a high level of trust in the scientific
community as it does not force a scientific opinion on its users (e.g. practicing
taxonomists, library researchers, etc.), but rather provides the tools for
experts to encode different views as science progresses. CONCLUSIONS: OpenBiodiv
O provides a conceptual model of the structure of a biodiversity publication and
the development of related taxonomic concepts. It also serves as the basis for
the OpenBiodiv Knowledge Management System.
PMID- 29347998
TI - Radiation exposure in transcatheter patent ductus arteriosus closure: time to
tune?
AB - OBJECTIVES: The aims of this study were to describe radiation level at our
institution during transcatheter patent ductus arteriosus occlusion and to
evaluate the components contributing to radiation exposure. BACKGROUND:
Transcatheter occlusion relying on X-ray imaging has become the treatment of
choice for patients with patent ductus arteriosus. Interventionists now work hard
to minimise radiation exposure in order to reduce risk of induced cancers.
METHODS: We retrospectively reviewed all consecutive children who underwent
transcatheter closure of patent ductus arteriosus from January 2012 to January
2016. Clinical data, anatomical characteristics, and catheterisation procedure
parameters were reported. Radiation doses were analysed for the following
variables: total air kerma, mGy; dose area product, Gy.cm2; dose area product per
body weight, Gy.cm2/kg; and total fluoroscopic time. RESULTS: A total of 324
patients were included (median age=1.51 [Q1-Q3: 0.62-4.23] years; weight=10.3
[6.7-17.0] kg). In all, 322/324 (99.4%) procedures were successful. The median
radiation doses were as follows: total air kerma: 26 (14.5-49.3) mGy; dose area
product: 1.01 (0.56-2.24) Gy.cm2; dose area product/kg: 0.106 (0.061-0.185)
Gy.cm2/kg; and fluoroscopic time: 2.8 (2-4) min. In multivariate analysis, a
weight >10 kg, a ductus arteriosus width <2 mm, complications during the
procedure, and a high frame rate (15 frames/second) were risk factors for an
increased exposure. CONCLUSION: Lower doses of radiation can be achieved with
subsequent recommendations: technical improvement, frame rate reduction,
avoidance of biplane cineangiograms, use of stored fluoroscopy as much as
possible, and limitation of fluoroscopic time. A greater use of echocardiography
might even lessen the exposure.
PMID- 29347999
TI - Whether you are a virus or a learned society-based virology journal, evolution is
critical for success!
PMID- 29347996
TI - The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2): study protocol for a
randomized controlled trial.
AB - BACKGROUND: Alzheimer's disease (AD) is characterized not only by cognitive and
functional decline, but also often by the presence of neuropsychiatric symptoms.
Apathy, which can be defined as a lack of motivation, is one of the most
prevalent neuropsychiatric symptoms in AD and typically leads to a worse quality
of life and greater burden for caregivers. Treatment options for apathy in AD are
limited, but studies have examined the use of the amphetamine, methylphenidate.
The Apathy in Dementia Methylphenidate Trial (ADMET) found that treatment of
apathy in AD with methylphenidate was associated with significant improvement in
apathy in two of three outcome measures, some evidence of improvement in global
cognition, and minimal adverse events. However, the trial only enrolled 60
participants who were followed for only 6 weeks. A larger, longer-lasting trial
is required to confirm these promising findings. METHODS: The Apathy in Dementia
Methylphenidate Trial 2 (ADMET 2) is a phase III, placebo-controlled, masked, 6
month, multi-center, randomized clinical trial targeted to enroll 200
participants with AD and apathy. Participants are randomly assigned 1:1 to 20 mg
methylphenidate per day prepared as four over-encapsulated tablets or to matching
placebo. The primary outcomes include (1) the mean difference in the
Neuropsychiatric Inventory Apathy subscale scores measured as change from
baseline to 6 months, and (2) the odds of having a given rating or better on the
modified AD Cooperative Study Clinical Global Impression of Change ratings at
month 6 compared with the baseline rating. Other outcomes include change in
cognition, safety, and cost-effectiveness measured at monthly follow-up visits up
to 6 months. DISCUSSION: Given the prevalence of apathy in AD and its impact on
both patients and caregivers, an intervention to alleviate apathy would be of
great benefit to society. ADMET 2 follows on the promising results from the
original ADMET to evaluate the efficacy of methylphenidate as a treatment for
apathy in AD. With a larger sample size and longer follow up, ADMET 2 is poised
to confirm or refute the original ADMET findings. TRIAL REGISTRATION:
ClinicalTrials.gov, NCT02346201 . Registered on 26 January 2015.
PMID- 29348000
TI - Biodegradation and Metabolism of Tetrabromobisphenol A (TBBPA) in the
Bioaugmented Activated Sludge Batch Bioreactor System by Heterotrophic and
Nitrifying Bacteria.
AB - Tetrabromobisphenol A [2,4'-isopropylidenebis(2,6-dibromophenol)] has been
identified in wastewater samples collected from the Guelph municipal wastewater
treatment plant (GWWTP). In order to assess the kinetics and metabolic mechanisms
of the dissolved TBBPA, bench scale experiments were completed with batch
bioreactors. The biodegradation test was conducted by taking aerobic sludge from
the conventional activated sludge reactor (CAS) and membrane bioreactor (MBR),
and bioaugmenting both reactors with soil based strains of Bacillus brevis and
Bacillus pumilus. This novel biodegradation process showed that the CAS
bioreactor had a biodegradation rate of 0.127 d-1, while the sludge from the MBR
had a biodegradation rate of 0.171 d-1. This is the first reported aerobic
biodegradation of TBBPA by heterotrophic and nitrifying bacteria in an activated
sludge bioreactor system. A tentative biotransformation metabolic scheme for
TBBPA biodegradation and metabolite formation has been proposed as well.
PMID- 29348001
TI - Zr-Metal Organic Framework and Derivatives for Adsorptive and Photocatalytic
Removal of Acid Dyes.
AB - To investigate effects of modification of MOFs on removal of acid dyes via
adsorption and photodegradation, zirconium-based MOF, UiO-66, and its derivatives
were synthesized. UiO-66 derivatives were prepared by using amine (NH2)
containing ligand and incorporating carbon nanotubes (CNTs) and reduced graphene
oxide (RGO). During the synthesis UiO-66-NH2, UiO-66-CNT and UiO-66-RGO, were
obtained, respectively. While UiO-66-NH2 showed the enhanced adsorption capacity
for acid dyes owing to the electrostatic attraction, CNTs were found to be the
most effective addition to enhance the adsorption of acid dyes. However, the
addition of RGO in UiO-66 (to form UiO-66-RGO) exhibited the highest removal
efficiency via photodegradation compared to UiO-66 and other derivatives probably
attributed to its unique layered morphology. The presence of NH2, CNTs and RGO
not only significantly improved the adsorption capacity for acid dyes but also
enabled these UiO-66 derivatives to exhibit photocatalytic activity under visible
light irradiation.
PMID- 29348002
TI - Evaluation of a Gravity Flow Membrane Bioreactor for Treating Municipal
Wastewater.
AB - The biomass concentrator reactor (BCR), a gravity flow membrane bioreactor
(MBR) design, was evaluated for use in treating a municipal wastewater stream.
The BCR operates with less than 2.5 cm of pressure head and uses a 3 to 4 mm
thick tortuous path membrane with pore size ranging from 18 to 28 MUm to achieve
solids separation. A two-stage, aerobic/anoxic reactor was evaluated for the
removal of chemical oxygen demand (COD), ammonia, total nitrogen, and solids
separation. The reactor was fed 72 L/day, with a hydraulic retention time of 9.3
hours, and had a solids retention time of 20 days. The influent COD was reduced
by 93%, whereas, influent ammonia was reduced below 0.1 mg/L and total nitrogen
was reduced by 53.7%. A lack of readily biodegradable COD limited denitrification
and thus total nitrogen removal. The reactor solids were retained completely in
the reactor by the membrane for the duration of testing.
PMID- 29348003
TI - The WaterHub at Emory University: Campus Resiliency through Decentralized Reuse.
AB - In the spring of 2015, Emory University in Atlanta, GA, commissioned an
innovative campuswide water reclamation and reuse system known as the
WaterHub(r). Treating up to 400,000 gallons each day, the system can recycle the
equivalent of two-thirds of the University's wastewater production and reduce the
campus water footprint by up to 40 percent.One of the first district-scale water
reuse systems in North America, the WaterHub mines wastewater from the campus
sewer system and repurposes it for beneficial reuse on campus. In its first year
of operation, the facility has treated more than 80 million gallons of campus
wastewater and is expected to save millions of dollars in utility costs for the
University over the next 20 years. The system represents a new age in commercial
scale water management in which onsite, urban water reclamation facilities may be
a new norm.
PMID- 29348004
TI - Predictors and Clinical Outcomes of Next-Day Discharge After Minimalist
Transfemoral Transcatheter Aortic Valve Replacement.
AB - OBJECTIVES: This study sought to investigate predictors and safety of next-day
discharge (NDD) after transcatheter aortic valve replacement (TAVR). BACKGROUND:
Information about predictors and safety of NDD after TAVR is limited. METHODS:
The study reviewed 663 consecutive patients who underwent elective balloon
expandable TAVR (from July 2014 to July 2016) at our institution. We first
determined predictors of NDD in patients who underwent minimalist transfemoral
TAVR. After excluding cases with complications, we compared 30-day and 1-year
outcomes between NDD patients and those with longer hospital stay using Cox
regression adjusting for the Predicted Risk of Mortality provided by the Society
of Thoracic Surgeons. The primary endpoint was the composite of mortality and
readmission at 1 year. RESULTS: A total of 150 patients had NDD after TAVR and
210 patients had non-NDD. Mean age and the Society of Thoracic Surgeons Predicted
Risk of Mortality were 80.7 +/- 8.8 years and 6.6 +/- 3.7%, respectively.
Predictors of NDD were male sex (odds ratio [OR]: 2.02; 95% confidence interval
[CI]: 1.28 to 3.18), absence of atrial fibrillation (OR: 1.62; 95% CI: 1.02 to
2.57), serum creatinine (OR: 0.71; 95% CI: 0.55 to 0.92), and age (OR: 0.95; 95%
CI: 0.93 to 0.98). As expected, 84% of patients with complications had non-NDD.
After excluding cases with complications, there was no difference in hazard rates
of the 30-day composite outcome between NDD and non-NDD (hazard ratio: 0.62; 95%
CI: 0.20 to 1.91), but the hazard of the composite outcome at 1 year was
significantly lower in the NDD group (hazard ratio: 0.47; 95% CI: 0.27 to 0.81).
This difference in the composite outcome can be explained by the lower hazard of
noncardiovascular related readmission in the NDD group. CONCLUSIONS: Factors
predicting NDD include male sex, absence of atrial fibrillation, lower serum
creatinine, and younger age. When compared with patients without complications
with a longer hospital stay, NDD appears to be safe, achieving similar 30-day and
superior 1-year clinical outcomes.
PMID- 29348005
TI - Next-Day Discharge After Transcatheter Aortic Valve Replacement: A Goal or a
Consequence?
PMID- 29348006
TI - Importance of Contrast Aortography With Lotus Transcatheter Aortic Valve
Replacement: A Post Hoc Analysis From the RESPOND Post-Market Study.
AB - OBJECTIVES: The aim of this post hoc analysis from the RESPOND (Repositionable
Lotus Valve System-Post-Market Evaluation of Real World Clinical Outcomes) post
market study was to assess the final implantation depth on the contrast aortogram
after Lotus valve (Boston Scientific, Marlborough, Massachusetts) transcatheter
aortic valve replacement (TAVR) and to correlate with permanent pacemaker
implantation (PPI) and paravalvular leak (PVL). BACKGROUND: Contrast aortography
allows for the assessment of implantation depth and PVL during and after TAVR.
Previous reports suggested an association between final device position and rates
of PPI and PVL. METHODS: The RESPOND study was a prospective, open-label, single
arm study in 41 centers evaluating outcomes after Lotus TAVR in routine clinical
practice. Aortograms were collected at the Erasmus Medical Center and analyzed by
researchers who were blinded to clinical outcomes. The primary analysis
correlated implantation depth with PPI and PVL and required aortograms in a
coaxial projection. The relation between implantation depth and need for PPI was
assessed by multivariate logistic regression, adjusting for pre-defined
confounders. A secondary analysis compared PVL analysis by contrast aortography
with transthoracic echocardiography (TTE) performed by the independent core
laboratory. RESULTS: A total of 724 angiographic studies were included in this
analysis. Mean Lotus implantation depth was 6.67 +/- 2.19 mm. The overall PPI
rate was 35%. PPI rate was lower with shallow implants (<6.5 mm: 21% vs. >=6.5
mm: 41%; p < 0.001). After adjustment for confounders, implantation depth
independently predicted need for PPI (odds ratio per 1-mm increment in depth:
1.200; 95% confidence interval: 1.091 to 1.319; p = 0.002). More than trivial PVL
was present in 23% by contrast aortography and in 8% by TTE. Implantation depth
was not correlated with PVL by contrast aortography or TTE (p = 0.342 and p =
0.149, respectively). PVL grading by contrast aortography and TTE was concordant
in 77%. CONCLUSIONS: In this post hoc analysis of the RESPOND study PPI was
highly correlated with implantation depth, whereas PVL was not. Higher Lotus
implantation may reduce need for PPI.
PMID- 29348007
TI - Assessing Implant Depth Using Aortography in Transcatheter Aortic Valve
Replacement: What You See May Not Be What You Get.
PMID- 29348009
TI - Valve in Valve for Failed Surgical Bioprostheses: Not for Everyone!
PMID- 29348008
TI - Impact of Pre-Existing Prosthesis-Patient Mismatch on Survival Following Aortic
Valve-in-Valve Procedures.
AB - OBJECTIVES: The aim of this study was to determine whether the association of
small label size of the surgical valve with increased mortality after
transcatheter valve-in-valve (ViV) implantation is, at least in part, related to
pre-existing prosthesis-patient mismatch (PPM) (i.e., a bioprosthesis that is too
small in relation to body size). BACKGROUND: Transcatheter ViV implantation is an
alternative for the treatment of patients with degenerated bioprostheses. Small
label size of the surgical valve has been associated with increased mortality
after ViV implantation. METHODS: Data from 1,168 patients included in the VIVID
(Valve-in-Valve International Data) registry were analyzed. Pre-existing PPM of
the surgical valve was determined using a reference value of effective orifice
area for each given model and size of implanted prosthetic valve indexed for body
surface area. Severe PPM was defined according to the criteria proposed by the
Valve Academic Research Consortium 2: indexed effective orifice area <0.65 cm2/m2
if body mass index is <30 kg/m2 and <0.6 cm2/m2 if BMI is >=30 kg/m2. The primary
study endpoint was 1-year mortality. RESULTS: Among the 1,168 patients included
in the registry, 89 (7.6%) had pre-existing severe PPM. Patients with severe PPM
had higher 30-day (10.3%, p = 0.01) and 1-year (unadjusted: 28.6%, p < 0.001;
adjusted: 19.3%, p = 0.03) mortality rates compared with patients with no severe
PPM (4.3%, 11.9%, and 10.9%, respectively). After adjusting for surgical valve
label size, Society of Thoracic Surgeons score, renal failure, diabetes, and
stentless surgical valves, presence of pre-existing severe PPM was associated
with increased risk for 1-year mortality (odds ratio: 1.88; 95% confidence
interval: 1.07 to 3.28; p = 0.03). Patients with severe PPM also more frequently
harbored high post-procedural gradients (mean gradient >=20 mm Hg). CONCLUSIONS:
Pre-existing PPM of the failed surgical valve is strongly and independently
associated with increased risk for mortality following ViV implantation.
PMID- 29348010
TI - Early Outcomes With the Evolut PRO Repositionable Self-Expanding Transcatheter
Aortic Valve With Pericardial Wrap.
AB - OBJECTIVES: This study sought to evaluate the Medtronic Evolut PRO Transcatheter
Aortic Valve System in patients with severe symptomatic aortic stenosis.
BACKGROUND: A next-generation self-expanding transcatheter aortic valve was
designed with an external pericardial wrap with the intent to reduce paravalvular
leak while maintaining the benefits of a low-profile, self-expanding, and
repositionable supra-annular valve. METHODS: The Medtronic Evolut PRO Clinical
Study included 60 patients undergoing transcatheter aortic valve replacement with
the Evolut PRO valve at 8 investigational sites in the United States. Clinical
outcomes at 30 days were evaluated using Valve Academic Research Consortium-2
criteria. The 2 primary safety endpoints were the incidence of all-cause
mortality at 30 days and the incidence of disabling stroke at 30 days. The
primary efficacy endpoint was the proportion of patients with no or trace
prosthetic valve regurgitation at 30 days. An independent echocardiographic core
laboratory (Mayo Clinic, Rochester, Minnesota) was used to adjudicate all
echocardiographic assessments. RESULTS: All 60 patients received the Evolut PRO
valve. At 30 days, 1 patient (1.7%) died and 1 patient (1.7%) experienced a
nonfatal disabling stroke. Paravalvular regurgitation at 30 days was absent or
trace in 72.4% of patients and was mild in the remainder of patients, with no
patients having worse than mild paravavlular leak. The mean atrioventricular
gradient was 6.4 +/- 2.1 mm Hg and effective orifice area was 2.0 +/- 0.5 cm2 at
30 days. CONCLUSIONS: The safety and efficacy results of this study support the
use of the Evolut PRO System for the treatment of severe symptomatic aortic
stenosis in patients who are at increased surgical risk, resulting in excellent
hemodynamics and minimal paravalvular leak (The Medtronic TAVR 2.0 US Clinical
Study; NCT02738853).
PMID- 29348011
TI - Sealing the Achilles Heel of Transcatheter Aortic Valve Replacement?
PMID- 29348012
TI - Coronary Embolus: An Underappreciated Cause of Acute Coronary Syndromes.
AB - Coronary embolism is the underlying cause of 3% of acute coronary syndromes but
is often not considered in the differential of acute coronary syndromes. It
should be suspected in the case of high thrombus burden despite a relatively
normal underlying vessel or recurrent coronary thrombus. Coronary embolism may be
direct (from the aortic valve or left atrial appendage), paroxysmal (from the
venous circulation through a patent foramen ovale), or iatrogenic (following
cardiac intervention). Investigations include transesophageal echocardiography to
assess the left atrial appendage and atrial septum and continuous
electrocardiographic monitoring to assess for paroxysmal atrial fibrillation. The
authors review the historic and contemporary published data about this important
cause of acute coronary syndromes. The authors propose an investigation and
management strategy for work-up and anticoagulation strategy for patients with
suspected coronary embolism.
PMID- 29348014
TI - Bioresorbable Vascular Scaffolds in In-Stent Restenosis.
PMID- 29348013
TI - Dose-Dependent Cardioprotection of Moderate (32 degrees C) Versus Mild (35
degrees C) Therapeutic Hypothermia in Porcine Acute Myocardial Infarction.
AB - OBJECTIVES: The study investigated whether a dose response exists between
myocardial salvage and the depth of therapeutic hypothermia. BACKGROUND: Cardiac
protection from mild hypothermia during acute myocardial infarction (AMI) has
yielded equivocal clinical trial results. Rapid, deeper hypothermia may improve
myocardial salvage. METHODS: Swine (n = 24) undergoing AMI were assigned to 3
reperfusion groups: normothermia (38 degrees C) and mild (35 degrees C) and
moderate (32 degrees C) hypothermia. One-hour anterior myocardial ischemia was
followed by rapid endovascular cooling to target reperfusion temperature. Cooling
began 30 min before reperfusion. Target temperature was reached before
reperfusion and was maintained for 60 min. Infarct size (IS) was assessed on day
6 using cardiac magnetic resonance, triphenyl tetrazolium chloride, and
histopathology. RESULTS: Triphenyl tetrazolium chloride area at risk (AAR) was
equivalent in all groups (p = 0.2), but 32 degrees C exhibited 77% and 91%
reductions in IS size per AAR compared with 35 degrees C and 38 degrees C,
respectively (AAR: 38 degrees C, 45 +/- 12%; 35 degrees C, 17 +/- 10%; 32 degrees
C, 4 +/- 4%; p < 0.001) and comparable reductions per LV mass (LV mass: 38
degrees C, 14 +/- 5%; 35 degrees C, 5 +/- 3%; 32 degrees C 1 +/- 1%; p < 0.001).
Importantly, 32 degrees C showed a lower IS AAR (p = 0.013) and increased
immunohistochemical granulation tissue versus 35 degrees C, indicating higher
tissue salvage. Delayed-enhancement cardiac magnetic resonance IS LV also showed
marked reduction at 32 degrees C (38 degrees C: 10 +/- 4%, p < 0.001; 35 degrees
C: 8 +/- 3%; 32 degrees C: 3 +/- 2%, p < 0.001). Cardiac output on day 6 was only
preserved at 32 degrees C (reduction in cardiac output: 38 degrees C, -29 +/-
19%, p = 0.041; 35 degrees C: -17 +/- 33%; 32 degrees C: -1 +/- 28%, p = 0.041).
Using linear regression, the predicted IS reduction was 6.7% (AAR) and 2.1% (LV)
per every 1 degrees C reperfusion temperature decrease. CONCLUSIONS: Moderate (32
degrees C) therapeutic hypothermia demonstrated superior and near-complete
cardioprotection compared with 35 degrees C and control, warranting further
investigation into clinical applications.
PMID- 29348015
TI - Reply: Bioresorbable Vascular Scaffolds in In-Stent Restenosis.
PMID- 29348016
TI - Effect of Modern Dose-Reduction Technology on the Exposure of Interventional
Cardiologists to Radiation in the Catheterization Laboratory.
PMID- 29348017
TI - A Pilot Study for Left Atrial Appendage Occlusion Guided by 3-Dimensional
Rotational Angiography Alone.
PMID- 29348018
TI - Myocardial Inflammation Predicts Remodeling and Neuroinflammation After
Myocardial Infarction.
AB - BACKGROUND: The local inflammatory tissue response after acute myocardial
infarction (MI) determines subsequent healing. Systemic interaction may induce
neuroinflammation as a precursor to neurodegeneration. OBJECTIVES: This study
sought to assess the influence of MI on cardiac and brain inflammation using
noninvasive positron emission tomography (PET) of the heart-brain axis. METHODS:
After coronary artery ligation or sham surgery, mice (n = 49) underwent serial
whole-body PET imaging of the mitochondrial translocator protein (TSPO) as a
marker of activated macrophages and microglia. Patients after acute MI (n = 3)
were also compared to healthy controls (n = 9). RESULTS: Infarct mice exhibited
elevated myocardial TSPO signal at 1 week versus sham (percent injected dose per
gram: 8.0 +/- 1.6 vs. 4.8 +/- 0.9; p < 0.001), localized to activated CD68+
inflammatory cells in the infarct. Early TSPO signal predicted subsequent left
ventricular remodeling at 8 weeks (rpartial = -0.687; p = 0.001). In parallel,
brain TSPO signal was elevated at 1 week (1.7 +/- 0.2 vs. 1.4 +/- 0.2 for sham; p
= 0.017), localized to activated microglia. After interval decline at 4 weeks,
progressive heart failure precipitated a second wave of neuroinflammation (1.8 +/
0.2; p = 0.005). TSPO was concurrently up-regulated in remote cardiomyocytes at
8 weeks (8.8 +/- 1.7, p < 0.001) without inflammatory cell infiltration,
suggesting mitochondrial impairment. Angiotensin-converting enzyme inhibitor
treatment lowered acute inflammation in the heart (p = 0.003) and brain (p =
0.06) and improved late cardiac function (p = 0.05). Patients also demonstrated
elevation of cardiac TSPO signal in the infarct territory, paralleled by
neuroinflammation versus controls. CONCLUSIONS: The brain is susceptible to acute
MI and chronic heart failure. Immune activation may interconnect heart and brain
dysfunction, a finding that provides a foundation for strategies to improve heart
and brain outcomes.
PMID- 29348019
TI - Imaging Dynamic Heart-Brain Interactions: Getting to the Heart of the Matter,
Gray and White.
PMID- 29348021
TI - Learning From Patients With Ultrarare Conditions: Cholesterol Hoof Beats.
PMID- 29348020
TI - Autosomal Recessive Hypercholesterolemia: Long-Term Cardiovascular Outcomes.
AB - BACKGROUND: Autosomal recessive hypercholesterolemia (ARH) is a rare lipid
disorder characterized by premature atherosclerotic cardiovascular disease
(ASCVD). There are sparse data for clinical management and cardiovascular
outcomes in ARH. OBJECTIVES: Evaluation of changes in lipid management,
achievement of low-density lipoprotein cholesterol (LDL-C) goals and
cardiovascular outcomes in ARH. METHODS: Published ARH cases were identified by
electronic search. All corresponding authors and physicians known to treat these
patients were asked to provide follow-up information, using a standardized
protocol. RESULTS: We collected data for 52 patients (28 females, 24 males; 31.1
+/- 17.1 years of age; baseline LDL-C: 571.9 +/- 171.7 mg/dl). During a mean
follow-up of 14.1 +/- 7.3 years, there was a significant increase in the use of
high-intensity statin and ezetimibe in combination with lipoprotein apheresis; in
6 patients, lomitapide was also added. Mean LDL-C achieved at nadir was 164.0 +/-
85.1 mg/dl (-69.6% from baseline), with a better response in patients taking
lomitapide (-88.3%). Overall, 23.1% of ARH patients reached LDL-C of <100 mg/dl.
During follow-up, 26.9% of patients had incident ASCVD, and 11.5% had a new
diagnosis of aortic valve stenosis (absolute risk per year of 1.9% and 0.8%,
respectively). No incident stroke was observed. Age (>=30 years) and the presence
of coronary artery disease at diagnosis were the major predictors of incident
ASCVD. CONCLUSIONS: Despite intensive treatment, LDL-C in ARH patients remains
far from targets, and this translates into a poor long-term cardiovascular
prognosis. Our data highlight the importance of an early diagnosis and treatment
and confirm the fact that an effective treatment protocol for ARH is still
lacking.
PMID- 29348022
TI - Identifying and Treating Young Patients at Risk for Cardiovascular Events.
PMID- 29348023
TI - Impaired Recovery of Left Ventricular Function in Patients With Cardiomyopathy
and Left Bundle Branch Block.
AB - BACKGROUND: Patients with left bundle branch block (LBBB) often respond to
cardiac resynchronization therapy (CRT) with left ventricular ejection fraction
(LVEF) improvement. Guideline-directed medical therapy (GDMT), not CRT, is first
line therapy for patients with reduced LVEF with LBBB. However, there are little
data on how patients with reduced LVEF and LBBB respond to GDMT. OBJECTIVES: This
study examined patients with cardiomyopathy and sought to assess rates of LVEF
improvement for patients with LBBB compared to other QRS morphologies. METHODS:
Using data from the Duke Echocardiography Laboratory Database, the study
identified patients with baseline electrocardiography and LVEF <=35% who had a
follow-up LVEF 3 to 6 months later. The study excluded patients with severe valve
disease, a cardiac device, left ventricular assist device, or heart transplant.
QRS morphology was classified as LBBB, QRS duration <120 ms (narrow QRS
duration), or a wide QRS duration >=120 ms but not LBBB. Analysis of variance
testing compared mean change in LVEF among the 3 groups with adjustment for
significant comorbidities and GDMT. RESULTS: There were 659 patients that met the
criteria: 111 LBBB (17%), 59 wide QRS duration >=120 ms but not LBBB (9%), and
489 narrow QRS duration (74%). Adjusted mean increase in LVEF over 3 to 6 months
in the 3 groups was 2.03%, 5.28%, and 8.00%, respectively (p < 0.0001). Results
were similar when adjusted for interim revascularization and myocardial
infarction. Comparison of mean LVEF improvement between patients with LBBB on
GDMT and those not on GDMT showed virtually no difference (3.50% vs. 3.44%). The
combined endpoint of heart failure hospitalization or mortality was highest for
patients with LBBB. CONCLUSIONS: LBBB is associated with a smaller degree of LVEF
improvement compared with other QRS morphologies, even with GDMT. Some patients
with LBBB may benefit from CRT earlier than guidelines currently recommend.
PMID- 29348024
TI - Cardiomyopathy and Left Bundle Branch Block: A Farewell to Drugs?
PMID- 29348026
TI - Imaging the Intersection of Oxidative Stress, Lipids, and Inflammation: Progress
Toward Personalized Care of Atherosclerosis.
PMID- 29348025
TI - PET/MR Imaging of Malondialdehyde-Acetaldehyde Epitopes With a Human Antibody
Detects Clinically Relevant Atherothrombosis.
AB - BACKGROUND: Oxidation-specific epitopes (OSEs) are proinflammatory, and elevated
levels in plasma predict cardiovascular events. OBJECTIVES: The purpose of this
study was to develop novel positron emission tomography (PET) probes to
noninvasively image OSE-rich lesions. METHODS: An antigen-binding fragment (Fab)
antibody library was constructed from human fetal cord blood. After multiple
rounds of screening against malondialdehyde-acetaldehyde (MAA) epitopes, the Fab
LA25 containing minimal nontemplated insertions in the CDR3 region was identified
and characterized. In mice, pharmacokinetics, biodistribution, and plaque
specificity studies were performed with Zirconium-89 (89Zr)-labeled LA25. In
rabbits, 89Zr-LA25 was used in combination with an integrated clinical
PET/magnetic resonance (MR) system. 18F-fluorodeoxyglucose PET and dynamic
contrast-enhanced MR imaging were used to evaluate vessel wall inflammation and
plaque neovascularization, respectively. Extensive ex vivo validation was carried
out through a combination of gamma counting, near infrared fluorescence,
autoradiography, immunohistochemistry, and immunofluorescence. RESULTS: LA25
bound specifically to MAA epitopes in advanced and ruptured human atherosclerotic
plaques with accompanying thrombi and in debris from distal protection devices.
PET/MR imaging 24 h after injection of 89Zr-LA25 showed increased uptake in the
abdominal aorta of atherosclerotic rabbits compared with nonatherosclerotic
control rabbits, confirmed by ex vivo gamma counting and autoradiography. 18F
fluorodeoxyglucose PET, dynamic contrast-enhanced MR imaging, and near-infrared
fluorescence signals were also significantly higher in atherosclerotic rabbit
aortas compared with control aortas. Enhanced liver uptake was also noted in
atherosclerotic animals, confirmed by the presence of MAA epitopes by
immunostaining. CONCLUSIONS: 89Zr-LA25 is a novel PET radiotracer that may allow
noninvasive phenotyping of high-risk OSE-rich lesions.
PMID- 29348027
TI - Implications of Underlying Mechanisms for the Recognition and Management of
Diabetic Cardiomyopathy.
AB - Heart failure is a complex clinical syndrome, the incidence and prevalence of
which is increased in diabetes mellitus, pre-diabetes, and obesity. Although this
may arise from underlying coronary artery disease, it often occurs in the absence
of significant major epicardial coronary disease, and most commonly manifests as
heart failure with preserved ejection fraction. Despite epidemiological evidence
linking diabetes to heart failure incidence and outcome, the presence of a
distinct primary "diabetic" cardiomyopathy has been difficult to prove, because
the link between diabetes and heart failure is confounded by hypertension,
microvascular dysfunction, and autonomic neuropathy. Nonetheless, several
mechanistic associations at systemic, cardiac, and cellular/molecular levels
explain different aspects of myocardial dysfunction, including impaired cardiac
relaxation, compliance, and contractility. This review seeks to describe recent
advances and limitations pertinent to integrating molecular mechanisms, clinical
screening, and potential therapeutic avenues for this condition.
PMID- 29348028
TI - Antithrombotic Therapy in Peripheral Artery Disease: Generating and Translating
Evidence Into Practice.
AB - Atherosclerotic cardiovascular (CV) disease remains a major health concern
affecting more than 200 million adults worldwide, and lower extremity peripheral
artery disease (PAD) is associated with significant morbidity and mortality.
Treatment strategies to reduce the burden of major adverse CV events and limb
events have mainly involved the use of antiplatelet and statin medications.
Unlike other types of atherosclerotic CV disease, the evidence base is not well
developed for therapies in patients with PAD. Recently, studies from subgroups of
patients with PAD and a large clinical trial of PAD patients have been published,
signaling a burgeoning interest in studying this higher risk population. This
review outlines the inherent CV risks of patients with PAD, risk reduction
strategies, emerging clinical trial data, and opportunities for the CV community
to generate evidence in real-world settings and translate evidence into practice
as new therapies become available.
PMID- 29348029
TI - Inorganic Nitrite Selectively Dilates Epicardial Coronary Arteries.
PMID- 29348030
TI - Cardiovascular Mortality Reduction With Empagliflozin in Patients With Type 2
Diabetes and Cardiovascular Disease.
PMID- 29348031
TI - Left Ventricular Systolic Dysfunction in Transplantation Donor Hearts: Another
Takotsubo Phenotype?
PMID- 29348032
TI - Reply: Transient Wall Motion Abnormalities in Donor Hearts With Improved Left
Ventricular Systolic Dysfunction: Takotsubo Revisited?
PMID- 29348033
TI - Myocardial Dysfunction Following Brain Death.
PMID- 29348034
TI - The new Brazilian legislation on access to the biodiversity (Law 13,123/15 and
Decree 8772/16).
PMID- 29348035
TI - Alzheimer's disease, cellular prion protein, and dolphins.
PMID- 29348036
TI - Increasing Traction for Discovery: The Research Domain Criteria Framework and
Neurodevelopmental Disorders.
PMID- 29348037
TI - Obligatory Processing of Task-Irrelevant Stimuli: A Hallmark of Autistic
Cognitive Style Within and Beyond the Diagnosis.
PMID- 29348038
TI - Children With Fragile X Syndrome Display Threat-Specific Biases Toward Emotion.
AB - BACKGROUND: Fragile X syndrome (FXS) is the most common form of inherited
intellectual disability. FXS is caused by a silencing of the FMR1 gene that
results in a loss or absence of the gene's protein product, fragile X mental
retardation protein. The phenotype of FXS is consistently associated with
heightened anxiety, although no previous study has investigated attentional bias
toward threat, a hallmark of anxiety disorders, in individuals with FXS. METHODS:
The current study employed a passive-viewing eye-tracking version of the dot
probe task to investigate attentional biases toward emotional faces in young
children with FXS (n = 47) and without FXS (n = 94). RESULTS: We found that the
FXS group showed a significantly greater bias toward threatening emotions than
toward positive emotions. This threat specificity was not seen in either a mental
age-matched group or a chronological age-matched group of typically developing
children. Unlike the typically developing groups, the FXS group showed no bias
toward positive emotion. CONCLUSIONS: The current study shows that children with
FXS have a significant bias toward threatening information, an attentional
profile that has been linked with anxiety. It also supports the use of eye
tracking methodology to index neural and attentional responses in young children
with FXS.
PMID- 29348039
TI - Face Processing Measures of Social Cognition: A Dimensional Approach to
Developmental Psychopathology.
AB - BACKGROUND: Social cognition impairments in neurodevelopmental disorders impact
functioning. Face processing is the most extensively studied aspect of social
cognition, commonly indexing this construct in neuropsychiatric disorders
compared with typically developing youths. Applying social cognition measures as
a Research Domain Criteria concept in the clinical arena requires establishing
cutoffs for intervention and identifying vulnerability for psychopathology across
disorders. This can be accomplished by comparing extreme performers across
multiple clinical symptom features. METHODS: The Philadelphia Neurodevelopmental
Cohort (N = 9498), a community sample of youths (8-21 years old), was assessed
with a structured interview (Kiddie Schedule for Affective Disorders and
Schizophrenia). The Penn Computerized Neurocognitive Battery was administered
measuring accuracy and response time on Executive, Episodic Memory, Complex
Cognition, and Social Cognition domains. We parsed participants by performance on
social cognition into tertiles and examined their neurocognitive and clinical
profiles. RESULTS: The top social cognition group outperformed the bottom group
in face memory and complex reasoning. Concerning symptoms, the top performing
group did not differ from the middle group, but the bottom performing group had
higher externalizing and psychosis symptoms. There were sex differences in social
cognition and symptom profiles but no sex * performance or sex * diagnosis *
domain interactions. CONCLUSIONS: Social cognition is supported by strong face
memory and complex reasoning skills. Poor performance portends more severe
externalizing and psychosis symptoms. That average performance is sufficient for
normative symptomatology suggests that interventions aimed at ameliorating social
cognition deficits, as measured here, could be effective in normalizing level of
symptoms.
PMID- 29348040
TI - Negative Valence in Autism Spectrum Disorder: The Relationship Between Amygdala
Activity, Selective Attention, and Co-occurring Anxiety.
AB - BACKGROUND: A critical agenda of the National Institutes of Health Research
Domain Criteria (RDoC) initiative is establishing whether domains within the RDoC
matrix are truly transdiagnostic. Rates of anxiety disorders are elevated in
autism spectrum disorder (ASD), but it is unclear whether the same mechanisms
contribute to anxiety in individuals with and without ASD. As changes in
selective attention are a hallmark of anxiety disorders in non-ASD samples, the
identification of these changes in ASD would support the transdiagnostic nature
of anxiety. METHODS: This functional magnetic resonance imaging study focused on
the negative valence domain from RDoC (manifest as anxiety symptoms) in youth
with ASD (n = 38) and typically developing control participants (n = 25). The
task required selective attention toward and away from social information (faces)
with negative and neutral affect. Participants underwent in-depth
characterization for both anxiety and ASD symptoms. RESULTS: Dimensional and
categorical measures of anxiety were significantly related to increased amygdala
activation-evidence of enhanced attentional capture by social information.
CONCLUSIONS: This pattern fits with decades of research among non-ASD samples
using selective attention and attentional bias paradigms, suggesting that anxiety
in ASD shares mechanisms with anxiety alone. Overall, results from this study
support the transdiagnostic nature of the negative valence domain from RDoC and
increase the likelihood that anxiety in ASD should be responsive to interventions
targeting maladaptive responses to negative information.
PMID- 29348042
TI - Zinc-aluminum oxide solid solution nanosheets obtained by pyrolysis of layered
double hydroxide as the photoanodes for dye-sensitized solar cells.
AB - Due to the superiority of metal-doped ZnO compared to TiO2, the Zn-M (M = Al3+,
Ga3+, Cr3+, Ti4+, Ce4+) mixed metal oxide solid solutions have been extensively
studied for photocatalytic and photovoltaic applications. In this work, a
systematic research has proceeded for the preparation of a zinc-aluminum oxide
semiconductor as a photoanode for the dye-sensitized solar cells (DSSCs) by a
simple pyrolysis route with the Zn-Al layered double hydroxide (LDH) as a
precursor. The Zn-Al oxide solid solution has been applied for DSSCs as an
electron acceptor, which is used to study the influence of different Al content
and sintering temperature on the device efficiency. Finally, the Zn-Al oxide
solid solution with calcination temperature 600 degrees C and Al 27 at.% content
exhibits the best performance. The photoelectric efficiency improved 100 times
when the Al3+ content decreased from 44 to 27 at.%. The ZnxAlyO solid solution
show a reasonable efficiency as photoanode materials in DSSCs, with the best
preliminary performance reported so far, and shows its potential application for
the photovoltaic devices.
PMID- 29348041
TI - Executive Dysfunction in Autism Spectrum Disorder Is Associated With a Failure to
Modulate Frontoparietal-insular Hub Architecture.
AB - BACKGROUND: Comorbid executive dysfunction in autism spectrum disorder (ASD) is a
barrier to adaptive functioning, despite remittance of core social-communication
symptoms. Network models of ASD address core symptoms but not comorbid executive
dysfunction. Following recent demonstrations in healthy adults that, with
increasing executive demands, hubs embedded within frontoparietal-insular control
networks interact with a more diverse set of networks, we hypothesized that the
capability of hubs to do so is perturbed in ASD and predicts executive behavior.
METHODS: Seventy-five 7- to 13-year-old children with ASD (n = 35) and age- and
IQ-matched typically developing control subjects (n = 40) completed both a
resting-state and a selective attention task functional magnetic resonance
imaging session. We assessed changes in the participation coefficient, a graph
theory metric indexing hubness, of 264 brain regions comprising 12 functional
networks between the two sessions. Parent reported executive impairment in
everyday life was measured using the Behavior Rating Inventory of Executive
Function. RESULTS: The participation coefficient of the frontoparietal-insular
cortex, including core nodes of the frontoparietal control and salience networks,
significantly increased in typically developing children but not in children with
ASD during the task relative to rest. Change in frontoparietal-insular
participation coefficient predicted Behavior Rating Inventory of Executive
Function scores indexing the ability to attend to task-oriented output, plan and
organize, and sustain working memory. CONCLUSIONS: Our results suggest that
executive impairments in ASD emerge from a failure of frontoparietal-insular
control regions to function as adaptive and integrative hubs in the brain's
functional network architecture. Our results also demonstrate the utility of
examining dynamic network function for elucidating potential biomarkers for
disorders with comorbid executive dysfunction.
PMID- 29348043
TI - Superhydrophobic coatings with high repellency to daily consumed liquid foods
based on food grade waxes.
AB - The applications of superhydrophobic coatings in daily life are receiving
increasing attention. Here, we report a general approach for preparing
superhydrophobic coatings with high repellency to daily consumed liquid foods
based on food grade waxes. The coatings are prepared by spray-coating the
homogeneous wax suspensions in ethanol followed by annealing at 40 degrees C.
The wax suspensions are formed by the heating dissolution-cooling precipitation
ultrasonication process thanks to the unique solubility of the waxes in ethanol.
Ultrasonication of the wax suspension is helpful to improve superhydrophobicity
by reducing the size of the wax microplatelets. Annealing at 40 degrees C could
enhance mechanical stability of the coatings. The coatings are superhydrophobic
with a water contact angle of 158.2 degrees and a sliding angle of 7.3 degrees .
The coatings are resistant to intense water jetting and immersion in corrosive
aqueous solutions. In addition, the coatings show excellent anti-adhesive
properties for various liquid foods including cola, honey, milk and yoghourt.
Moreover, the coatings are applicable onto different substrates (e.g., glass
slide, PET plate and polyethylene plate) and could be prepared using different
waxes (e.g., paraffin wax, beeswax and microcrystalline wax). We believe that the
wax superhydrophobic coatings could find applications in various fields such as
anti-adhesion of liquid foods, fruit preservation and anti-bioadhesion, etc.
PMID- 29348044
TI - Wetting of flat gradient surfaces.
AB - Gradient, chemically modified, flat surfaces enable directed transport of
droplets. Calculation of apparent contact angles inherent for gradient surfaces
is challenging even for atomically flat ones. Wetting of gradient, flat solid
surfaces is treated within the variational approach, under which the contact line
is free to move along the substrate. Transversality conditions of the variational
problem give rise to the generalized Young equation valid for gradient solid
surfaces. The apparent (equilibrium) contact angle of a droplet, placed on a
gradient surface depends on the radius of the contact line and the values of
derivatives of interfacial tensions. The linear approximation of the problem is
considered. It is demonstrated that the contact angle hysteresis is inevitable on
gradient surfaces. Electrowetting of gradient surfaces is discussed.
PMID- 29348045
TI - Supplementary motor area-primary motor cortex facilitation in younger but not
older adults.
AB - Growing evidence implicates a decline in white matter integrity in the age
related decline in motor control. Functional neuroimaging studies show
significant associations between functional connectivity in the cortical motor
network, including the supplementary motor area (SMA), and motor performance.
Dual-coil transcranial magnetic stimulation studies show facilitatory connections
between SMA and the primary motor cortex (M1) in younger adults. Here, we
investigated whether SMA-M1 facilitation is affected by age and whether the
strength of SMA-M1 facilitation is associated with bilateral motor control. Dual
coil transcranial magnetic stimulation was used to measure SMA-M1 connectivity in
younger (N = 20) and older adults (N = 18), and bilateral motor control was
measured with the assembly subtest of the Purdue Pegboard and clinical measures
of dynamic balance. SMA-M1 facilitation was seen in younger but not older adults,
and a significant positive association was found between SMA-M1 facilitation and
bimanual performance. These results show that SMA-M1 facilitation is reduced in
older adults compared to younger adults and provide evidence of the functional
importance of SMA-M1 facilitation.
PMID- 29348046
TI - Synthesis of sulfamide analogues of deoxthymidine monophosphate as potential
inhibitors of mycobacterial cell wall biosynthesis.
AB - The recently discovered enzyme Mycobacterium tuberculosis thymidine monophosphate
kinase (TMPKmt), which catalyses the phosphorylation of deoxythymidine
monophosphate (dTMP) to give deoxythymidine diphosphate (dTDP), is indispensable
for the growth and survival of M. tuberculosis as it plays an essential role in
DNA synthesis. Inhibition of TMPKmt is an attractive avenue for the development
of novel anti-tuberculosis agents. Based on the premise that sulfamide may be a
suitable isostere of phosphate, deoxythymidine analogues comprising various
substituted sulfamides at C5' were modelled in silico into the active site of
TMPKmt (PDB accession code: 1N5K) using induced-fit docking methods. A selection
of modelled compounds was synthesized, and their activity as inhibitors of TMPKmt
was evaluated. Three compounds showed competitive inhibition of TMPKmt in the
micromolar range (10-50 MUM). Compounds were tested in vitro for anti
mycobacterial activity against M. smegmatis: three compounds showed weak anti
mycobacterial activity (MIC 250 MUg/mL).
PMID- 29348047
TI - Effects of inorganic ions and natural organic matter on the aggregation of
nanoplastics.
AB - The aggregation of nanoplastics (NPs) is a key issue in understanding the dynamic
nature of NPs in the environment. The aggregation of NPs under various
environmental conditions has not yet been studied. We investigated the influences
of inorganic ions and natural organic matter (NOM) on polystyrene (PS) NPs
aggregation in solutions. Results showed that PS NPs remained stable in wide
ionic strength solutions of NaCl (1-100 mM) and CaCl2 (0.1-15 mM), and only in
low ionic strength FeCl3 solutions (0.01 mM). However, obvious PS NPs aggregation
was observed in FeCl3 solutions with an increase in ionic strength (0.1 and 1
mM). Moreover, NOM had a negligible effect on PS NPs aggregation in all ionic
strengths of NaCl and CaCl2 solutions and in low ionic strength FeCl3 solutions
(0.01 mM). However, NOM reduced PS NPs aggregation in an intermediate ionic
strength FeCl3 (0.1 mM) solution and increased aggregation in a high ionic
strength FeCl3 (1 mM) solution. Based on the theoretical analysis of interaction
forces among PS NPs, the Derjaguin-Landau-Verwey-Overbeek force was a contributor
governing PS NPs aggregation either in the absence or presence of NOM. In
addition, other factors, including electrostatic heterogeneity of PS NPs
surfaces, steric repulsion induced by NOM, and clusters formed via bridging
effect in the presence of NOM also contributed to altered PS NPs aggregation
under selected conditions. The PS NPs-NOM clusters were directly observed using a
cryogenic scanning electron microscope.
PMID- 29348048
TI - Identification of number and type of cations in water-soluble Cs+ and Na+
calix[4]arene-bis-crown-6 complexes by using ESI-TOF-MS.
AB - The treatment of cesium-contaminated wastewater has become one of the biggest
issues. The selective Cs+ removal from wastewater containing competitive alkali
metal ions such as Na+ is desired to reduce the volume of sludge. Therefore, the
present work focused on water-soluble calix[4]arene-bis-crown-6 (W-BisC6) to
selectively capture Cs+. For characterization of the complex, UV-vis spectroscopy
is commonly used, however, due to the limited availability of information it can
be hard to quickly identify the specific structures of some complexes. In this
work, the electrospray ionization time of flight spectrometry (ESI-TOF-MS) is
successfully utilized to identify the number and type of cations in W-BisC6
cation complexes. ESI-TOF-MS accurately recognized 4 types of complex (W-BisC6
Na+, W-BisC6-Cs+, W-BisC6-2Na+, W-BisC6-Na+-Cs+), and the experimental and
simulated results were almost perfectly matched. It also revealed the difficulty
of W-BisC6-2Cs+ complex formation under the present conditions. Thus, this
technique is significantly helpful for rapid identification of the specific
structures of complexes during Cs+-contaminated wastewater treatment.
PMID- 29348050
TI - Do estimates of blood loss differ between student midwives and midwives? A
multicenter cross-sectional study.
AB - OBJECTIVE: the principal objective of this study was to assess the quality of
blood loss estimates by midwives and student midwives. The secondary objectives
were: to assess the intraobserver agreement of visual blood estimates and the
rate of underestimation of blood loss by participants, and to estimate the
sensitivity, specificity, and negative likelihood ratio of these estimates for
clinically pertinent blood losses (>= 500mL and >= 1000mL). DESIGN: multicenter
cross-sectional study. SETTING: thirty-three French maternity units and 35 French
midwifery schools participated in this study. PARTICIPANTS: volunteer French
midwifery students (n = 463) and practicing midwives (n = 578). INTERVENTION: an
online survey showed 16 randomly ordered photographs of 8 different simulated
blood quantities (100, 150, 200, 300, 500, 850, 1000, and 1500mL) with a
reference 50-mL image in each photo and asked participants to estimate the blood
loss. The visual blood loss estimates were compared with Fisher's exact test.
Intraobserver agreement for these estimates was assessed with a weighted kappa
coefficient, and the negative predictive values (probability of no hemorrhage
when visual estimate was negative) were calculated from prevalence rates in the
literature. FINDINGS: of the 16,656 estimates obtained, 34.1% were accurate,
37.2% underestimated the quantity presented, and 28.7% overestimated it. Analyses
of the intraobserver reproducibility between the two estimates of the same
photograph showed that agreement was highest (weighted kappa >= 0.8) for the
highest values (1000mL, 1500mL). For each volume considered, students
underestimated blood loss more frequently than midwives. In both groups, the
negative predictive values regarding postpartum hemorrhage (PPH) diagnosis
(severe or not) were greater than 98%. KEY CONCLUSIONS AND IMPLICATIONS FOR
PRACTICE: student midwives tended to underestimate the quantity of blood loss
more frequently than the midwives. Postpartum hemorrhage (>= 500mL) was always
identified, but severe postpartum hemorrhage (>= 1000mL) was identified in fewer
than half the cases. These results should be taken into account in training both
student midwives and practicing professionals.
PMID- 29348049
TI - CuI and CuII complexes with phosphine derivatives of fluoroquinolone antibiotics
A comparative study on the cytotoxic mode of action.
AB - In this paper, we present a comparative study on the cytotoxic mode of action of
copper(I) and copper(II) complexes with phosphine derivatives of fluoroquinolone
antibiotics (ciprofloxacin HCp and norfloxacin HNr). The in vitro cytotoxic
activity of four new compounds was tested against two selected cancer cell lines.
All complexes exhibited much better cytotoxicity against both cell lines than
unmodified fluoroquinolone antibiotics, their phosphines (PCp, PNr), chalcogenide
derivatives (oxides: OPCp, OPNr; sulfides: SPCp, SPNr and selenides: SePCp,
SePNr) and previously described by us complexes with phosphines derived from
different fluoroquinolones: lomefloxacin (HLm) and sparfloxacin (HSf) as well as
cisplatin. Apoptosis, observed at a great predominance, was induced by all
studied complexes. Importantly, it was concluded that coordination compounds with
Cu(I) ion ([CuI-PNr] and [CuI-PCp]) were much more active than those with Cu(II)
ion ([OPNr-CuII], [OPCp-CuII]), even though the highest efficacy to produce
reactive oxygen species, participating in overall cytotoxicity, was proved for
copper(II) complexes among all studied compounds. Herein, we discuss not only
results obtained for copper(I)/(II) complexes with phosphines derived from HNr
and HCp but we also compare them to previously described data for complexes with
HLm and HSf derivatives. This is the first insight into a structure-activity
relationship of copper complexes with phosphine derivatives of fluoroquinolone
antibiotics.
PMID- 29348051
TI - Midwives understanding of physical activity guidelines during pregnancy.
AB - OBJECTIVE: to examine the current level of understanding held by midwives
regarding the NICE physical activity guidelines in the UK, and to investigate the
physical activity guidance given to women during pregnancy. DESIGN: an 11
question online survey comprising of a mixture of closed and open ended
questions. SETTING: data reflects participants sampled across the United Kingdom.
PARTICIPANTS: fifty-nine midwives completed the online survey MEASUREMENTS AND
FINDINGS: an electronic survey was used to explore the midwives understanding of
physical activity guidelines during pregnancy, and the advice they offered to
women in their care. Qualitative content analysis was used to gain a more in
depth understanding of midwife knowledge. Two per cent of midwives correctly
identified the physical activity guidelines, with 44% giving partially correct
responses, 25% giving incorrect responses and 29% unsure of what the guidelines
are. Despite the low level of correct responses, 59% of respondents reported they
were confident or very confident in answering questions regarding physical
activity. Only 4% of respondents reported having access to continual professional
development (CPD) in the area of PA guidance. KEY CONCLUSIONS: there appears to
be a misplaced confidence amongst midwives in their knowledge of the NICE PA
guidelines for pregnancy. IMPLICATIONS FOR PRACTICE: as physical inactivity can
be detrimental for the health of both mother and baby, there is a clear need for
better dissemination of the current and future NICE physical activity guidelines
in primary health care settings. The current study determined a substantial lack
of CPD in the area of PA guidance, which may be a contributing factor to the lack
of knowledge of the guidelines. As such, increasing CPD may in turn improve the
accuracy of the advice given to pregnant women and consequently benefit the
health of both mother and baby.
PMID- 29348053
TI - Multimodality imaging of endocrine immune related adverse events: a primer for
radiologists.
AB - Immune-related endocrine adverse events occur in up to one third of patients
treated with immune checkpoint inhibitors. The purpose of this article is to
provide a comprehensive review of the multimodality imaging features of the
different immune-related endocrine adverse events. In this article, we will
introduce the different types of immune checkpoint inhibitors used in clinical
practice, and for each endocrine organ affected we will describe the clinical
presentation, the multimodality imaging features at presentation and after
treatment, and the possible differential diagnosis.
PMID- 29348052
TI - Thirty-day complication rate of percutaneous gastrojejunostomy and gastrostomy
tube insertion using a single-puncture, dual-anchor technique.
AB - PURPOSE: Our objective was to assess 30-day mortality and complication rates
associated with percutaneous enteral feeding tube insertion using a single
puncture, dual-suture anchor gastropexy and peel-away sheath technique. We
explored differences in complications based on indication and gastrostomy versus
gastrojejunostomy tube. METHODS: A retrospective review was conducted of adult
patients undergoing fluoroscopically guided gastrojejunostomy (GJ) and
gastrostomy (G) tube insertions between July 2011 and 2014 by five interventional
radiologists at a single tertiary care centre. A single-puncture dual-anchor
gastropexy technique with a peel-away sheath was used for all patients.
Complications within 30 day post-procedure were classified based on the Society
of Interventional Radiology Standards of Practice for Gastrointestinal Access.
Procedure-related mortality and complication rates, as well as indication
specific complication rates, were compared between GJ and G groups. RESULTS: 559
consecutive patients underwent G (86) or GJ (473) tube insertion. Primary
technical success was 100%. Nine major (1.6%) and 60 minor (10.7%) complications
occurred for an overall complication rate of 12.3%. The 30-day complication rate
was significantly higher for GJ compared to G tube insertion (13.5% v. 5.8%, p =
.049). There was a trend toward a higher 30-day minor complication rate for the
GJ group (11.8% v. 4.7%, p = .057), but no significant difference between groups
with respect to major complications (1.7% v. 1.2%, p = 1.0). Four procedure
related deaths occurred resulting in an overall procedure-related mortality of
0.7%. No significant difference in the procedure-related mortality was found
between GJ and G groups (0.6% v. 1.2%, p = .49). CONCLUSION: The 30-day major
complication and procedure-related mortality rates from G and GJ tube insertion
are low when using a single-puncture, dual-anchor gastropexy technique. GJ tube
insertion is associated with a higher overall complication rate, likely due to
more minor complications, but may avoid long-term adverse events.
PMID- 29348054
TI - Evaluation of sulfane sulfur bioeffects via a mitochondria-targeting selenium
containing near-infrared fluorescent probe.
AB - As a crucial member in antioxidant regulatory systems, sulfane sulfur plays
essential roles in cytoprotective mechanisms by directly eliminating ROS and
altering ROS-mediated redox signaling. Despite the rising interests in sulfane
sulfur, there only a few bio-compatible methods are available for its direct
detection. Moreover, most of the existing methods cannot meet the requirements of
real-time detection due to the reactive and labile chemical properties of sulfane
sulfur. Therefore, we strive to clarify the mutual relationship between
mitochondria sulfane sulfur and ROS under hypoxia stress. Herein, we report a
near-infrared fluorescent probe Mito-SeH for the selective imaging of
mitochondrial sulfane sulfur in cells and in vivo under hypoxia stress. Mito-SeH
includes three moieties: a selenol group (SeH) as the stronger sulfur-acceptor; a
near-infrared azo-BODIPY fluorophore as the fluorescent modulator; a lipophilic
alkyltriphenylphosphonium cation as the mitochondrial delivery. Mito-SeH exhibits
excellent selectivity and sensitivity towards the detection of mitochondria
sulfane sulfur. The hypoxia response behavior of Mito-SeH is evaluated in
monolayer cell and three-dimensional multicellular spheroid to clarify the
relationship between sulfane sulfur and hypoxia. We confirm that sulfane sulfur
protection mechanism against hypoxia is to inhibition of caspase-dependent
apoptosis through directly scavenging ROS pathway. The probe is also applied to
measurement of sulfane sulfur in ex vivo-dissected organs of hypoxic mouse model,
as well as the probe is successfully used for real-time monitoring the changes of
sulfane sulfur and ROS in acute ischemia mice model. We suggest that sulfane
sulfur may be a novel therapeutic agent for hypoxia-induced injury.
PMID- 29348055
TI - High-resolution structures of mitochondrial ribosomes and their functional
implications.
AB - Mitochondrial ribosomes (mitoribosomes) almost exclusively synthesize essential
components of the oxidative phosphorylation machinery. Dysfunction of
mitochondrial protein biosynthesis leads to human diseases and plays an important
role in the altered metabolism of cancer cells. Recent developments in cryo
electron microscopy enabled the structural characterization of complete yeast and
mammalian mitoribosomes at near-atomic resolution. Despite originating from
ancestral bacterial ribosomes, mitoribosomes have diverged in their composition
and architecture. Mitoribosomal proteins are larger and more numerous, forming an
extended network around the ribosomal RNA, which is expanded in yeast and highly
reduced in mammals. Novel protein elements at the entrance or exit of the mRNA
channel imply a different mechanism of mRNA recruitment. The polypeptide tunnel
is optimized for the synthesis of hydrophobic proteins and their co-translational
membrane insertion.
PMID- 29348056
TI - Achieving local and global shared realities: distance guides alignment to
specific or general social influences.
AB - Humans routinely navigate a multitude of potential social influences, ranging
from specific individual's opinions to general social norms and group values.
Whereas specific social influences afford opportunities to achieve shared inner
states with particular individuals, general social influences afford
opportunities to achieve shared inner states with broader groups. We review
recent theory and evidence examining how people tune into different kinds of
social influence in the service of shared reality. We argue that the distance of
an attitude object (e.g. how far away it is in time or space) systematically
influences what kind of social influence informs people's attitudes. As an
attitude object grows more distant, people's attitudes increasingly align with
general (vs. specific) social influences.
PMID- 29348057
TI - Peanut straw biochar increases the resistance of two Ultisols derived from
different parent materials to acidification: A mechanism study.
AB - The mechanisms for increasing soil pH buffering capacity (pHBC) and soil
resistance to acidification by peanut straw biochar were investigated by
undertaking indoor incubation and simulated acidification experiments using two
Ultisols derived from tertiary red sandstone and quaternary red earth. The
biochar increased the pHBC and resistance of the two Ultisols to acidification.
The addition of 3% biochar increased the pHBC of the two Ultisols by 76% and 25%,
respectively. The increased resistance of the soils to acidification led to the
inhibition to decrease in soil pH and the activation of soil Al during
acidification. The protonation of carboxyl groups on the biochar surface was the
main mechanism responsible for resisting acidification of the Ultisols when the
pH was between 4.5 and 7.0. The higher soil pH (>6.0) after biochar application
and the large number of carboxyl groups on the biochar surface were essential if
biochar was to significantly increase the resistance of soils to acidification.
PMID- 29348058
TI - Elemental assessment of vegetation via portable X-ray fluorescence (PXRF)
spectrometry.
AB - Elemental concentrations in vegetation are of critical importance, whether
establishing plant essential element concentrations (toxicity vs. deficiency) or
investigating deleterious elements (e.g., heavy metals) differentially extracted
from the soil by plants. Traditionally, elemental analysis of vegetation has been
facilitated by acid digestion followed by quantification via inductively coupled
plasma (ICP) or atomic absorption (AA) spectroscopy. Previous studies have
utilized portable X-ray fluorescence (PXRF) spectroscopy to quantify elements in
soils, but few have evaluated the vegetation. In this study, a PXRF spectrometer
was employed to scan 228 organic material samples (thatch, deciduous leaves,
grasses, tree bark, and herbaceous plants) from smelter-impacted areas of
Romania, as well as National Institute of Standards and Technology (NIST)
certified reference materials, to demonstrate the application of PXRF for
elemental determination in vegetation. Samples were scanned in three conditions:
as received from the field (moist), oven dry (70 degrees C), and dried and
powdered to pass a 2 mm sieve. Performance metrics of PXRF models relative to ICP
atomic emission spectroscopy were developed to asses optimal scanning conditions.
Thatch and bark samples showed the highest mean PXRF and ICP concentrations
(e.g., Zn, Pb, Cd, Fe), with the exceptions of K and Cl. Validation statistics
indicate that the stable validation predictive capacity of PXRF increased in the
following order: oven dry intact < field moist < oven dried and powdered. Even
under field moist conditions, PXRF could reasonably be used for the determination
of Zn (coefficient of determination, R2val 0.86; residual prediction deviation,
RPD 2.72) and Cu (R2val 0.77; RPD 2.12), while dried and powdered samples allowed
for stable validation prediction of Pb (R2val 0.90; RPD 3.29), Fe (R2val 0.80;
RPD 2.29), Cd (R2val 0.75; RPD 2.07) and Cu (R2val 0.98; RPD of 8.53). Summarily,
PXRF was shown to be a useful approach for quickly assessing the elemental
concentration in vegetation. Future PXRF/vegetation research should explore
additional elements and investigate its usefulness in evaluating phytoremediation
effectiveness.
PMID- 29348059
TI - Synthesis and evaluation of a superabsorbent-fertilizer composite for maximizing
the nutrient and water use efficiency in forestry plantations.
AB - Reducing fertilizer use is a priority in the quest for sustainable forestry
systems. In short rotation Eucalyptus plantations, NPK pellets are routinely
added to the seedling's top soil layer at planting, potentially leading to
increased seedling mortality, nutrient loss and environmental degradation. To
address this triple challenge, the development of efficient fertilization
practices is essential. In the present work, we synthesized a crosslinked acrylic
cellulosic superabsorbent composite (SAPH-BAL) containing small amounts of
specific nutrients integrated in the polymer matrix. We analyzed the composite's
chemical and rheological properties, and assessed the viability of Eucalyptus
plantations supplied with it at planting. Physiological measurements confirmed
the suitability of SAPH-BAL in greenhouse-grown potted seedlings subjected to
different growth conditions, showing that it efficiently delivers nutrients while
protecting seedlings from drought stress. Field experiments carried out at ten
South American locations covering an ample range of environmental conditions
confirmed the beneficial effect of SAPH-BAL on growth and survival in comparison
to the conventional fertilization scheme (superabsorbent + 75 g NPK).
Furthermore, it was found that plants treated with SAPH-BAL were less affected by
the differences in rainfall regimes during the experiments compared to those
fertilized conventionally. To the best of our knowledge this is the first report
describing the successful use of superabsorbents for root targeted delivery of
fertilizers in forestry operations.
PMID- 29348060
TI - Exposure to workplace smoking bans and continuity of daily smoking patterns on
workdays and weekends.
AB - INTRODUCTION: Individuals may compensate for workplace smoking bans by smoking
more before or after work, or escaping bans to smoke, but no studies have
conducted a detailed, quantitative analysis of such compensatory behaviors using
real-time data. METHODS: 124 daily smokers documented smoking occasions over
3weeks using ecological momentary assessment (EMA), and provided information on
real-world exposure to smoking restrictions and type of workplace smoking policy
(full, partial, or no bans). Mixed modeling and generalized estimating equations
assessed effects of time of day, weekday (vs weekend), and workplace policy on
mean cigarettes per hour (CPH) and reports of changing location to smoke.
RESULTS: Individuals were most likely to change locations to smoke during
business hours, regardless of work policy, and frequency of EMA reports of
restrictions at work was associated with increased likelihood of changing
locations to smoke (OR=1.11, 95% CI 1.05-1.16; p<0.0001). Workplace smoking
policy, time block, and weekday/weekend interacted to predict CPH (p<0.01), such
that individuals with partial work bans -but not those with full bans - smoked
more at night (9pm - bed) on weekdays compared to weekends. CONCLUSIONS: There
was little evidence that full bans interfered with subjects' smoking during
business hours across weekdays and weekends. Smokers largely compensate for
exposure to workplace smoking bans by escaping restrictions during business
hours. Better understanding the effects of smoking bans on smoking behavior may
help to improve their effectiveness and yield insights into determinants of
smoking in more restrictive environments.
PMID- 29348061
TI - Effects of wavelength mixing ratio and photoperiod on microalgal biomass and
lipid production in a two-phase culture system using LED illumination.
AB - Blue and red light-emitting diodes (LEDs) were used to study the effects of
wavelength mixing ratios, photoperiod regimes, and green wavelength stress on
Nannochloropsis salina, Isochrysis galbana, and Phaeodactylum tricornutum cell
biomass and lipid production. The maximum specific growth rates of I. galbana and
P. tricornutum were obtained under a 50:50 mixing ratio of blue and red
wavelength LEDs; that of N. salina was obtained under red LED. Maximum cell
biomass for N. salina and P. tricornutum was 0.75 and 1.07 g dcw/L, respectively,
obtained under a 24:0 h light/dark cycle. However, the maximum I. galbana biomass
was 0.89 g dcw/L under an 18:6 h light/dark cycle. The maximum lipid contents for
N. salina, I. galbana, and P. tricornutum were 49.4, 63.3 and 62.0% (w/w),
respectively, after exposure to green LED. Eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA) were obtained 1% in P. tricornutum and 2% in I.
galbana.
PMID- 29348062
TI - Improving sewage sludge composting by addition of spent mushroom substrate and
sucrose.
AB - The effects of spent mushroom substrate (SMS) and sucrose (S) amendment on
emissions of nitrogenous gas (mainly NH3 and N2O) and end products quality of
sewage sludge (SS) composting were evaluated. Five treatments were composted for
20 days in laboratory-scale using SS with different dosages of SMS and S, without
additive amended treatment used as control. The results indicated that SMS
amendments especially combination with S promoted dehydrogenase activity, CO2
production, organic matter degradation and humification in the composting, and
maturity indices of composting also showed that the 30%SMS+2%S treatment could be
much more appropriate to improve the composting process, such as total Kjeldahl
nitrogen, nitrification index, humic acids/fulvic acids ratio and germination
index, while the emissions of NH3 and N2O were reduced by 34.1% and 86.2%,
respectively. These results shown that the moderate addition of SMS and S could
improve the compost maturity and reduce nitrogenous gas emission.
PMID- 29348063
TI - Production of acids and alcohols from syngas in a two-stage continuous
fermentation process.
AB - A two-stage continuous system with two stirred tank reactors in series was
utilized to perform syngas fermentation using Clostridium carboxidivorans. The
first bioreactor (bioreactor 1) was maintained at pH 6 to promote acidogenesis
and the second one (bioreactor 2) at pH 5 to stimulate solventogenesis. Both
reactors were operated in continuous mode by feeding syngas (CO:CO2:H2:N2;
30:10:20:40; vol%) at a constant flow rate while supplying a nutrient medium at
different flow rates of 8.1, 15, 22 and 30 ml/h. A cell recycling unit was added
to bioreactor 2 in order to recycle the cells back to the reactor, maintaining
the OD600 around 1 in bioreactor 2 throughout the experimental run. When
comparing the flow rates, the best results in terms of solvent production were
obtained with a flow rate of 22 ml/h, reaching the highest average outlet
concentration for alcohols (1.51 g/L) and the most favorable alcohol/acid ratio
of 0.32.
PMID- 29348064
TI - Magnetic mapping of distribution of wood ash used for fertilization of forest
soil.
AB - The effect of wood-ash fertilization on forest soils has been assessed mainly
through geochemical methods (e.g., content of soil organic matter or nutrients).
However, a simple and fast method of determining the distribution of the ash and
the extent of affected soil is missing. In this study we present the use of
magnetic susceptibility, which is controlled by Fe-oxides, in comparing the
fertilized soil in the forest plantation of pine and oak with intact forest soil.
Spatial and vertical distribution of magnetic susceptibility was measured in an
oak and pine plantation next to stems of young plants, where wood ash was applied
as fertilizer. Pattern of the susceptibility distribution was compared with that
in non-fertilized part of the plantation as well as with a spot of intact natural
forest soil nearby. Our results show that the wood-ash samples contain
significant amount of ferrimagnetic magnetite with susceptibility higher than
that of typical forest soil. Clear differences were observed between magnetic
susceptibility of furrows and ridges. Moreover, the dispersed ash remains
practically on the surface, does not penetrate to deeper layers. Finally, our
data suggest significant differences in surface values between the pine and oak
plants. Based on this study we may conclude that magnetic susceptibility may
represent a simple and approximate method of assessing the extent of soil
affected by wood-ash.
PMID- 29348065
TI - The behaviour of 236U in the North Atlantic Ocean assessed from numerical
modelling: A new evaluation of the input function into the Arctic.
AB - A numerical model, previously validated with other radionuclides, was applied to
simulate the dispersion of 236U released from European nuclear fuel reprocessing
plants in the North Atlantic and Shelf Seas using a published reconstruction of
Sellafield and La Hague releases. Model results are in better agreement with
observations if the lowest estimation of such releases are used. This implies
that approximately 40kg of 236U has been discharged from Sellafield. It was found
that adsorption of 236U on bed sediments of the shallow European Shelf Seas plays
an essential role in its dispersion patterns. This contrasts strongly with the
more conservative behaviour of 129I in the same area. This has two important
implications in the use of 236U as oceanographic tracer; i) special care must be
taken in coastal areas, as sediments might act as sinks and sources of 236U; ii)
the annual input function of 236U into the Arctic is not directly controlled by
the annual discharges from Sellafield and La Hague, since sediments from the
Irish, Celtic and North Sea modulate and smooth the signal. Only 52% of the total
releases enter into the Arctic Ocean.
PMID- 29348066
TI - Multi-scale measurements show limited soil greenhouse gas emissions in Kenyan
smallholder coffee-dairy systems.
AB - Efforts have been made in recent years to improve knowledge about soil greenhouse
gas (GHG) fluxes from sub-Saharan Africa. However, data on soil GHG emissions
from smallholder coffee-dairy systems have not hitherto been measured
experimentally. This study aimed to quantify soil GHG emissions at different
spatial and temporal scales in smallholder coffee-dairy farms in Murang'a County,
Central Kenya. GHG measurements were carried out for one year, comprising two
cropping seasons, using vented static chambers and gas chromatography. Sixty
rectangular frames were installed on two farms comprising the three main cropping
systems found in the area: 1) coffee (Coffea arabica L.); 2) Napier grass
(Pennisetum purpureum); and 3) maize intercropped with beans (Zea mays and
Phaseolus vulgaris). Within these fields, chambers were allocated on fertilised
and unfertilised locations to capture spatial variability. Cumulative annual
fluxes in coffee plots ranged from 1 to 1.9kgN2O-Nha-1, 6.5 to 7.6MgCO2-Cha-1 and
-3.4 to -2.2kgCH4-Cha-1, with 66% to 94% of annual GHG fluxes occurring during
rainy seasons. Across the farm plots, coffee received most of the N inputs and
had 56% to 89% higher emissions of N2O than Napier grass, maize and beans. Within
farm plots, two to six times higher emissions were found in fertilised hotspots -
around the perimeter of coffee trees or within planted maize rows - than in
unfertilised locations between trees, rows and planting holes. Background and
induced soil N2O emissions from fertiliser and manure applications in the three
cropping systems were lower than hypothesized from previous studies and empirical
models. This study supplements methods and underlying data for the quantification
of GHG emissions at multiple spatial and temporal scales in tropical, smallholder
farming systems. Advances towards overcoming the dearth of data will facilitate
the understanding of synergies and tradeoffs of climate-smart approaches for low
emissions development.
PMID- 29348067
TI - Physiological response and transcription profiling analysis reveals the role of
H2S in alleviating excess nitrate stress tolerance in tomato roots.
AB - Soil secondary salinization caused by excess nitrate addition is one of the major
obstacles in greenhouse vegetable production. Excess nitrate inhibited the growth
of tomato plants, while application of 100 MUM H2S donor NaHS efficiently
increased the plant height, fresh and dry weight of shoot and root, root length,
endogenous H2S contents and L-cysteine desulfhydrases activities. NaHS altered
the oxidative status of nitrate-stressed plants as inferred by changes in
reactive oxygen species (ROS) accumulation and lipid peroxidation accompanied by
regulation of the activities of superoxide dismutase (SOD), peroxidase (POD),
catalase (CAT), ascorbate peroxidase (APX). Besides, NaHS increased the nitric
oxide (NO) and total S-nitrosothiols (SNOs) contents, nitrate reductase (NR)
activities and decreased the S-nitrosoglutathione reductase (GSNOR) activities
under nitrate stress. Furthermore, microarray analysis using the Affymetrix
Tomato GeneChip showed that 5349 transcripts were up-regulated and 5536
transcripts were down-regulated under NaHS and excess nitrate stress treatment,
compared to the excess nitrate stress alone. The differentially expressed genes
(log2 fold change >2 or < -2) of up-regulated (213) and down-regulated (271)
genes identified were functionally annotated and subsequently classified into 9
functional categories. These categories included metabolism, signal transduction,
defence response, transcription factor, protein synthesis and protein fate,
transporter, cell wall related, hormone response, cell death, energy and unknown
proteins. Our study suggested exogenous NaHS might enhance excess nitrate stress
tolerance of tomato plants by modulating ROS and reactive nitrogen species (RNS)
signaling and downstream transcriptional adjustment, such as defence response,
signal transduction and transcription factors.
PMID- 29348068
TI - Advantages of titanium xerogel over titanium tetrachloride and polytitanium
tetrachloride in coagulation: A mechanism analysis.
AB - Titanium xerogel coagulant (TXC) worked better than titanium tetrachloride (TC)
and polytitanium chloride (PTC) in a wider pH/dose range for the removal of
turbidity. However, the underlying mechanisms were not comprehensively
understood. In this work, the better coagulation performance of TXC than TC and
PTC was systematically elucidated from the following aspects: the physicochemical
properties of the three coagulants, the removal of turbidity and organic matter,
and the complexation reactions in coagulation. The results demonstrate that the
merits of TXC were attributable to the following characteristics: (1) the higher
surface charge density/total surface site concentration/isoelectric point of TXC
hydrolysates, (2) the formation of TXC hydrolysates with a net-work structure,
and (3) the strong binding affinity of TXC hydrolysates to organic matter caused
by the bonded acetylacetone in the TXC framework. In short, the hydrolysis
behavior of TXC significantly differed from both its precursor, TC, and the
prehydrolyzed PTC. The difference in the hydrolysis of TXC was derived from the
gelation process, which led to the polymerization of Ti in a way different from
prehydrolyzation. The elucidation of the hydrolysis mechanisms is useful for the
better application of Ti-based coagulants and may shed light on the preparation
of other metal salts.
PMID- 29348069
TI - Thermomechanical processing of In-containing beta-type Ti-Nb alloys.
AB - In this study, the effect of thermomechanical processing on microstructure
evolution of the indium-containing beta-type Ti alloys (Ti-40Nb)-3.5In and (Ti
36Nb)-3.5In was examined. Both alloys show an increased beta-phase stability
compared to binary alloys due to In additions. This leads to a reduced alpha''
phase fraction in the solution treated and recrystallized state in the case of
(Ti-36Nb)-3.5In and to the suppression of stress-induced alpha'' formation and
deformation twinning for (Ti-40Nb)-3.5In. The mechanical properties of the alloys
were subsequently studied by quasistatic tensile tests in the recrystallized
state, revealing reduced Young's modulus values of 58GPa ((Ti-40Nb)-3.5In) and
56GPa ((Ti-36Nb)-3.5In) compared to 60GPa as determined for Ti-40Nb. For both In
containing alloys the ultimate tensile strength is in the range of 560MPa. Due to
the suppressed alpha'' formation, (Ti-40Nb)-3.5In exhibits a linear elastic
deformation behavior during tensile loading together with a low Young's modulus
and is therefore promising for load-bearing implants.
PMID- 29348070
TI - Rational approach to highly potent and selective apoptosis signal-regulating
kinase 1 (ASK1) inhibitors.
AB - Many diseases are believed to be driven by pathological levels of reactive oxygen
species (ROS) and oxidative stress has long been recognized as a driver for
inflammatory disorders. Apoptosis signal-regulating kinase 1 (ASK1) has been
reported to be activated by intracellular ROS and its inhibition leads to a down
regulation of p38-and JNK-dependent signaling. Consequently, ASK1 inhibitors may
have the potential to treat clinically important inflammatory pathologies
including renal, pulmonary and liver diseases. Analysis of the ASK1 ATP-binding
site suggested that Gln756, an amino acid that rarely occurs at the GK+2
position, offered opportunities for achieving kinase selectivity for ASK1 which
was applied to the design of a parallel medicinal chemistry library that afforded
inhibitors of ASK1 with nanomolar potency and excellent kinome selectivity. A
focused optimization strategy utilizing structure-based design resulted in the
identification of ASK1 inhibitors with low nanomolar potency in a cellular assay,
high selectivity when tested against kinase and broad pharmacology screening
panels, and attractive physicochemical properties. The compounds we describe are
attractive tool compounds to inform the therapeutic potential of ASK1 inhibition.
PMID- 29348071
TI - A focused fragment library targeting the antibiotic resistance enzyme -
Oxacillinase-48: Synthesis, structural evaluation and inhibitor design.
AB - beta-Lactam antibiotics are of utmost importance when treating bacterial
infections in the medical community. However, currently their utility is
threatened by the emergence and spread of beta-lactam resistance. The most
prevalent resistance mechanism to beta-lactam antibiotics is expression of beta
lactamase enzymes. One way to overcome resistance caused by beta-lactamases, is
the development of beta-lactamase inhibitors and today several beta-lactamase
inhibitors e.g. avibactam, are approved in the clinic. Our focus is the
oxacillinase-48 (OXA-48), an enzyme reported to spread rapidly across the world
and commonly identified in Escherichia coli and Klebsiella pneumoniae. To guide
inhibitor design, we used diversely substituted 3-aryl and 3-heteroaryl benzoic
acids to probe the active site of OXA-48 for useful enzyme-inhibitor
interactions. In the presented study, a focused fragment library containing 49 3
substituted benzoic acid derivatives were synthesised and biochemically
characterized. Based on crystallographic data from 33 fragment-enzyme complexes,
the fragments could be classified into R1 or R2 binders by their overall binding
conformation in relation to the binding of the R1 and R2 side groups of imipenem.
Moreover, binding interactions attractive for future inhibitor design were found
and their usefulness explored by the rational design and evaluation of merged
inhibitors from orthogonally binding fragments. The best inhibitors among the
resulting 3,5-disubstituted benzoic acids showed inhibitory potential in the low
micromolar range (IC50 = 2.9 MUM). For these inhibitors, the complex X-ray
structures revealed non-covalent binding to Arg250, Arg214 and Tyr211 in the
active site and the interactions observed with the mono-substituted fragments
were also identified in the merged structures.
PMID- 29348072
TI - Structure-based development of an osteoprotegerin-like glycopeptide that blocks
RANKL/RANK interactions and reduces ovariectomy-induced bone loss in mice.
AB - Osteoporosis is a metabolic bone disease characterized by low bone mass and micro
architectural deterioration of bone, for which the underlying mechanism is an
imbalance between bone resorption and bone remodeling. The protein-protein
interactions between receptor activator of nuclear factor-kappaB ligand (RANKL),
RANK (its receptor), and osteoprotegerin (OPG), are known to mediate the
development and activation of osteoclasts in bone remodeling, and are regarded as
a pivotal therapeutic target for the treatment of osteoporosis. Herein, we
disclose the successful development of a novel glycopeptide (OM-2), the structure
of which is based on the key interacting sites of the reported RANKL and OPG
crystal structure. OM-2 exhibited potent binding affinity with RANKL and
resistance to degradation by protease enzymes. It also blocked RANKL/RANK
interactions, and inhibited osteoclastogenesis in vitro. In vivo studies
confirmed that OM-2 could effectively reduce bone loss and inhibit osteoclast
activation in ovariectomized (OVX) mice at a dosage of 20.0 mg/kg/day.
Accordingly, OM-2 is suggested as a therapeutic candidate for postmenopausal
osteoporosis (PMOP) and osteoclastogenesis-related diseases like rheumatoid
arthritis (RA). More importantly, its identification validates our structure
based strategy for the development of drugs that target the RANKL/RANK/OPG
system.
PMID- 29348073
TI - Rate of switch from bipolar depression into mania after morning light therapy: A
historical review.
AB - Light therapy (LT) is efficacious for bipolar depression with effect sizes
equivalent to those in antidepressant pharmacotherapy trials. Patients with
bipolar disorder (BD) show a 15-40% rate of manic switches during antidepressant
drug treatment. The rate of manic switches during LT has never been estimated. We
searched all the literature studies reporting effects of antidepressant LT in BD.
41 studies described 799 patients with BD treated with antidepressant LT, from
among which 7 (0.9%) switched into mania and 11 (1.4%) switched into hypomania.
The method of assessment of treatment-emergent symptoms significantly influenced
the detection of switches into mania: 0% when no method was reported, 0.8% with
clinical mental state examination, and 3% with rating scales (chi2 = 14.805, d.f.
4, p = 0.005). The rate of switch increased to 18.8% when considering the 16
patients with rapid-cycling BD. Switches occurred independent of treatment
modality (light intensity, duration, and circadian timing of administration). The
available literature shows that the highest reported rate of switch from bipolar
depression into mania after LT is closely similar to the 4% switch rate expected
during the placebo treatment of BD, thus not justifying specific concerns when
using this treatment option.
PMID- 29348074
TI - Standardized medical image registration for radiological identification of
decedents based on paranasal sinuses.
AB - Image registration software is frequently used in clinical radiology, e.g., for
follow-up diagnosis. To a certain extent, the radiological identification of
decedents (RadID) is comparable to a clinical follow-up diagnosis, in that two
datasets from different dates are compared in terms of their anatomical
characteristics (e.g., paranasal sinuses) or surgical implants. Due to the
increasing use of computed tomography (CT) for head examinations in clinical
radiology and the increased use of postmortem CT (PMCT) in forensic imaging, the
comparison of three-dimensional (3D) clinical CT (termed as antemortem CT (AMCT)
in this article) and PMCT datasets for RadID is becoming increasingly practical.
In particular, the comparison of paranasal sinuses in AMCT and PMCT imaging is
considered a suitable and reliable modality for RadID. However, previous
publications regarding RadID based on comparisons of 3D datasets have not
considered the implementation of image registration to provide software-side
support for RadID. This article demonstrates and evaluates the use of a standard
medical image registration procedure for RadID by comparing paranasal sinuses.
PMID- 29348076
TI - Association between serum arsenic levels and gestational diabetes mellitus: A
population-based birth cohort study.
AB - Gestational diabetes mellitus (GDM) is a common obstetric complication with
adverse effects on both mothers and their children. Previous studies revealed the
link between Arsenic (As) exposure and incidence of diabetes mellitus (DM), but
the data on the association between maternal As exposure and GDM is scarce. We
examined this association among a population-based birth cohort. As
concentrations were determined at multiple time points during pregnancy by ICP
MS. The association between As levels and GDM prevalence was examined using
logistic regression model after adjustment for confounders. A total of 419
(12.85%) women were diagnosed with GDM. The incidences of GDM gradually increased
with increasing quartiles of As levels with significant trend. As levels were
associated with the GDM (95%CI: 1.29-2.43) at only the 4th quartile in the first
trimester. After adjustment for maternal age, prepregnancy body mass index (BMI),
monthly income, gestational age and parity, the association remains significant
(95%CI: 1.22-2.38). Stratified analyses showed the associations were largely
limited to normal maternal age (95%CI: 1.19-3.04) and normal weight women (95%CI:
1.18-2.66). Our study showed an association between As and GDM in a birth cohort
and explored first trimester may be the critical period for As associated GDM.
This association was universal in the general pregnant population of normal age
and of normal weight.
PMID- 29348075
TI - Benzalkonium chloride, benzethonium chloride, and chloroxylenol - Three
replacement antimicrobials are more toxic than triclosan and triclocarban in two
model organisms.
AB - With the recent ban of triclosan (TCS) and triclocarban (TCC) from some personal
care products, many replacement antimicrobial compounds have been used. Yet the
potential health risk and environmental impact of these replacement compounds are
largely unknown. Here we investigated the toxicological effects of three commonly
used replacement antimicrobials, benzalkonium chloride (BAC), benzethonium
chloride (BEC), and chloroxylenol (CX) to two model organisms, the nematode C.
elegans and zebrafish (Danio rerio), and compared them to the banned TCS and TCC.
We found that these replacement compounds are not any safer than the banned
antimicrobials. In the worm, at least one of the three, BAC, showed comparable
toxicity to TCS from organismal to molecular levels, with toxic effects occurring
at lower hundred MUg/L to lower mg/L levels. In the fish, all three compounds at
the tested concentration ranges (0.05-5 mg/L) showed toxicity effects to
zebrafish embryos, indicated by hatching delay or inhibition, embryonic
mortality, morphological malformations, and neurotoxicity. BAC was the most toxic
among the three, with acute lethal toxicity occurring at environmentally relevant
concentrations (hundreds of MUg/L), which is comparable to the banned TCC.
However, the toxicity effects of BAC and TCC occurred within different time
windows, potentially suggesting different mechanisms of toxicity. CX was the only
compound that induced a "body curvature" phenotype among the five compounds
examined, suggesting a unique mode of toxic action for this compound.
Furthermore, all five compounds except TCS induced neurotoxicity in fish larvae,
indicated by alterations in secondary motoneuron axonal projections. Such
neurotoxicity has been largely understudied for these antimicrobials in the past
years and calls for further investigations in terms of its underlying mechanisms
and ecological significance. These findings strongly indicate that scrutiny
should be put on these replacement compounds before their introduction into
massive use in personal care products.
PMID- 29348077
TI - Effects of Cordyceps sinensis on macrophage function in high-fat diet fed rats
and its anti-proliferative effects on IMR-32 human neuroblastoma cells.
AB - Macrophages have been considered an elusive yet emerging therapeutic target in
tumor development since they are an important component in tumor
microenvironment. The purpose of the present study was to evaluate the effect of
C. sinensis on macrophage function (a component of tumor microenvironment which
can alter the virulence of cancer) in high-fat diet fed rats. IMR-32 human
neuroblastoma cell cytotoxicity was also investigated. The following parameters
were observed to evaluate macrophage function: superoxide anion, hydrogen
peroxide, nitric oxide, lysosomal volume and phagocytic capacity. High fat diet
(HFD) plus C. sinensis supplementation promoted a decreased superoxide anion and
hydrogen peroxide levels as well as lysosomal volume and phagocytic capacity.
Nitric oxide was increased in the same group. In summary, C. sinensis offered an
important anti-tumoral perspective from the standpoint of the tumor
microenvironment and in vitro IMR-32 cytotoxicity.
PMID- 29348078
TI - A clinical study showing altered antioxidants profile in patients with
hypertension.
AB - We compared the plasma antioxidants level of normal control group with that of
hypertensive patients in order to test the hypothesis "that antioxidants level
has been diminished in hypertensive patients and that antioxidants are
interconnected with each other making a network. The plasma and red blood cells
antioxidants level of newly diagnosed hypertensive patients [(n=30), (mean age 53
years), (mean systolic BP 158 mmHg, mean diastolic BP 100 mmHg)] were compared to
those of the control subjects [(n=30), (mean age 50 years), (mean systolic BP 126
mmHg, mean diastolic BP 90 mmHg)] using liquid chromatography linked with
electrochemical detector (HPLC-ECD). The data was analyzed by Minitab software at
a 95% confidence interval (p<0.05) as significant. The comparison between the two
groups was made applying 2-sample and paired t-test. The individual concentration
of antioxidants in both plasma and red blood cells of hypertensive patients was
lower in comparison with that of control group while the oxidized/reduced ratios
of these antioxidants were higher in hypertensive patients in comparison with
that of control group. It is concluded that antioxidants level had been
diminished in the hypertensive patients when compared with control group. The
overall concentration of all antioxidants has been diminished in the oxidative
stress induced pathological conditions which confirm that the studied
antioxidants are working in a network. This study may be helpful for the
recommendation of antioxidants intervention.
PMID- 29348079
TI - Synthesis, optimization and biological evaluation of 99mTc-digoxin as possible
cardiac imaging agent.
AB - Heart imaging radiopharmaceuticals could improve the diagnostic value of routine
heart scanning for detecting cardiac disorders. The aim of the study was to
prepare high radiochemical purity 99mTc-Digoxin in a yield of about 98%. The
optimal conditions for labelling were as follows: 100MUg of Digoxin, 2MUg of
SnCl2*2H2O, room temperature (25+/-1 degrees C), reaction
retention time of 30 min at pH 7. Under these conditions, the radiochemical yield
of 99mTc-Digoxin reaches 98%. In vivo bio distribution was performed
in normal Swiss Albino mice at different time intervals after administration of
99mTc-Digoxin.Scintigraphic study of 99mTc-Digoxin was
performed in rabbits. The heart uptake of 99mTc-Digoxin was
sufficiently high and thus may be a potential myocardial imaging
radiopharmaceutical applicable in cardiology.
PMID- 29348080
TI - Squid ink polysaccharide prevents chemotherapy induced injury in the testes of
reproducing mice.
AB - The present study was conducted to investigate the preventive effects of squid
ink polysaccharides (SIP) on the damage of sperm and reproduction induced by
cyclophosphamide that is most commonly used for treating clinically cancers. Male
Kunming mice exposed to cyclophosphamide were administered with SIP and were
sacrificed to determine sperm parameters, testicular antioxidant ability and
reproductive capacity. Data indicated that cyclophosphamide caused obvious
changes in mice such as significant reduction (P<0.01) of glutathione reductase
activity (GR), vitamin C (Vc) content and total antioxidant capacity (T-AOC) in
the testes, as well as elevation (P<0.01) of abnormal rates of sperm and fetus,
and a decrease in the total fetal count and average fetal count (P<0.01), were
totally alleviated by SIP. From these findings it can be concluded that SIP
decreases chemotherapeutic damage to sperm and reproduction in mice induced by
cyclophosphamide.
PMID- 29348081
TI - Evaluation of antioxidant and antimicrobial activities of Bergenia ciliata Sternb
(Rhizome) crude extract and fractions.
AB - Biologically, screening of medicinal plants extracts have been since pre-historic
to determine the antioxidants and antimicrobial profile. The present study was
aimed to investigate and evaluate crude extract and different fractions of
Bergenia ciliata Sternb (rhizome) for bioactivity which is most considerable
medicinal plants. The chloroform fraction was found to be highly anti-oxidative
with the IC50 value (4.15+/-0.82) as compare to ethyl acetate and n-hexane
fraction. In addition, neither crude extract nor any fraction showed inhibition
against fungal strains, i.e. Aspergillus flavus and Aspergillus niger.
Furthermore, the crude extract and fractions of B. ciliata (rhizome) exhibiting
promising activities against Bacillus atrophoeus, Bacillus subtilis, Kleibsiella
pneumonia and Pseudomonas aeruginosa strains. In summary, B. ciliata is
recommended as a source of bioactive compounds which might be used against
oxidative stress and drug resistance bacteria.
PMID- 29348082
TI - Nephrotoxic effects of Valeriana wallichii.
AB - Aminoglycosides are the commonly used antibiotics against Gram negative bacteria.
Their clinical applications are limited due to nephrotoxic side effects.
Therefore, the current study was undertaken in an attempt to increase the use of
these drugs without causing nephrotoxicity by exploring the nephroprotective
effects of a medicinal plant with high flavonoid contents and strong antioxidant
properties, namely Valeriana wallichii. A daily dose of 200mg/kg of the extract
derived from V. wallichii was employed for a period of three weeks. The results
obtained revealed that co-therapy of extract with gentamicin protected some
changes in renal functions; however, failed to provide a complete protection as
assessed by biochemical, physiological and histological parameters. It can be
concluded from the current findings that V. wallichii failed to deliver
protective effects against gentamicin induced renal damage in spite of strong
flavonoid contents and antioxidant properties.
PMID- 29348083
TI - GC-MS and HPLC profiles of phenolic fractions of the leaf of Telfairia
occidentalis.
AB - Telfairia occidentalis possesses high antioxidant activity. However, the
antioxidant components of the plant have not yet been identified. This study was
undertaken to identify the phenolics in the leaf of the plant. Extract and
fractions of the leaf of the plant were analysed using the HPLC and GCMS. HPLC
analysis revealed the presence of gallic acid (22.19MUg/mg), catechin
(29.17MUg/mg), caffeic acid (9.17MUg/mg), ferulic acid (0.94MUg/mg), sinapic acid
(1.91 MUg/mg) and 4-hydroxy benzoic acid (43.86 MUg/mg) in the aqueous extract.
Phenolics fraction contained gallic acid (0.88 MUg/mg), catechin (2.70MUg/mg),
caffeic acid (7.92MUg/mg), ferulic acid (2.72MUg/mg), benzoic acid (6.36MUg/mg),
p-coumaric acid (1.48MUg/mg), quercetin (12.00MUg/mg). Only caffeic acid
(2.50MUg/mg), ferulic acid (0.44MUg/mg) and quercetin (8.50MUg/mg) were detected
in the flavonoid fraction. While GCMS analysis showed the presence of
methylparaben; ethylparaben; benzoic acid; 4-hydroxy-2-methoxy-3,5,6-trimethyl-,
methyl ester; 4-hydroxy-3-methoxy; phenol, 5-methoxy-2-(methoxymethyl)-; phenol,
5-methoxy-2, 3- dimethyl; and phenol, 2-(2-benzothiazolyl)-. This study is the
first to reveal the identity of some phenolics components of the leaf of
Telfairia occidentalis.
PMID- 29348084
TI - Molecular characterization of autosomal recessive non syndromic hearing loss in
selected families from District Mardan, Pakistan.
AB - Deafness is the most common sensory disorder, which affects 1/1000 neonates
globally. Genetic factors are major contributors for hearing impairment. This
study was conducted to explore the linkage of DFNB loci and their mutations with
NSHL in selected Pakistani families. We included 10 families with history of
deafness from district Mardan, Pakistan. Blood sample (5ml) along with personal
and clinical information was collected from the available family members
including both diseased and un-affected individuals. Genomic DNA was amplified
using loci specific STR markers to investigate the linkage of DFNB loci. Family
found linked with DFNB4 locus was screened for SLC26A4 mutations. One out of the
ten explored families was found linked with DFNB4 locus which was further
investigated for SLC26A4 gene mutation through direct DNA sequencing. Two novel
mutations were observed in the studied family, one at splice donor site
(164+2T>G) and the other at position 164+5C>G only in the affected members of the
linked family. DFNB4 locus was found linked in the present study which harbors
SLC26A4 gene. The novel mutation of SLC26A4 gene at the splice donor site results
in skipping of the first coding exon and thus can lead to loss of expression of
SLC26A4 product in the inner ear.
PMID- 29348085
TI - Toxic effect of common poisonous plants of district Bannu, Khyber Pakhtunkhwa,
Pakistan.
AB - The present paper was a part of Ph.D research work, conducted during the year
2014, in which 87 poisonous plants belonging to 54 genera, were collected,
documented and preserved in the herbarium of Bannu, Department of Botany UST,
Bannu Khyber Pakhtunkwa Pakistan. The plants were identified botanically,
arranged alphabetically along with their Latin name, family name, common name,
poisonous parts, toxicity, affects, toxin and their effects. Aim of the study was
to induce awareness in the local people of district Bannu about the poisonous
effects of the commonly used plants. Data about poisonous effect were collected
from the local experienced and mostly old age people through questionnaire. Some
information were collected from a number of veterinary texts and literature. The
most important plants genera studied in the area were Brassica 6 species
(11.11%), Lathyrus 5 spp (9.26%), Astragalus, Euphorbia and Prunus were with 4
spp (7.40%). Datura, Jatropha, Ranunculus, Solanum and Sorghum were with 3 spp
(5.56%) while Allium, Amaranthus, Chenopodium, Melilotus and Taxus were with 2
spp (3.70%). These 15 genera contribute 48 species (55.17 %) while the remaining
39 genera have single species each and contribute 44.83% to the total poisonous
flora of the research area. Other important poisonous plants were Anagallis
arvensis L., Cannabis sativa, Datura stramonium L., D. metel L., Euphorbia
species, Heliotropium europaeum, Ipomoea tricolor, Jatropha curcas, Lolium
temulentum L., Malus domestica, Mangifera indica L., Medicago sativa L.,
Melilotus alba Desr., M. officinalis (L.) Lam., Mirabilis jalapa L., Narcissus
tazetta, Nicotiana tabacum L., Sorghum halepense (L) Pers., and Xanthium
strumarium. It was concluded that the local population had poor knowledge about
the poisonous effect of the plants and the present research work was anticipated
for use by health care professionals, veterinarians, farmers, homeowners, as well
as botanically curious individuals.
PMID- 29348086
TI - Pharmaceutical equivalent dissertation of Metformin hydrochloride brands.
AB - The aim of study is to establish pharmaceutical equivalence of different brands
of Metformin tablets available in Karachi, Pakistan. The quality control
parameters which are studied are weight variation test, hardness test, thickness,
friability, disintegration and dissolution specified by BP/USP (British and
United State Pharmacopoeia). Weight variation and hardness value requirement was
complied by all brands. Disintegration time for all brands was within range i.e.
15 minutes and also complies with the BP/USP recommendation. All brands showed
more than 90% drug release within forty five minutes. The present conclusion
suggests that almost all the brands of Metformin that are available in Karachi
meet the specification for quality control analysis. Assay performed by HPLC by
keeping flow rate of 1.0 ml/min of the mobile phase and the quantitative
evaluation at 225 nm was performed. The retention time of Metformin was found to
be 2.5min. Method suitability for the quantitative determination of the drugs was
proved by validation according to the International Conference on Harmonization
(ICH) guidelines.
PMID- 29348087
TI - Phytochemical screening and antibacterial activity of different solvent extracted
samples of Arisaema jacquemontii.
AB - The current research was carried out to assess the antibacterial activities and
phytochemical analysis of the methanol, n-hexane, ethyl acetate, n-butanol
soluble fractions and aqueous extracts of the tubers of Arisaema jacquemontii.
All the extracts were tested for their antibacterial potential at 1, 2 and 3 mg
disc-1 concentrations against 6 bacterial strains through disc diffusion
suseptibility assay. The data suggested that different extracts showed varying
degree of growth inhibition against the tested microbes. Statistical analysis
revealed that n-hexane and ethyl acetate soluble fractions significantly
inhibited the growth of all the bacterial strains at the tested concentrations.
Moderate activities were recorded for n-butanol and methanolic extracted samples
at different concentrations against all the tested strains of bacteria. P.
aeruginosa, S. aureus and X. campestris showed resistance to all the tested
concentrations of the aqueous extract. B. subtilis and K. pneumoniae were
resistant at 1 and 2 mg disc-1 concentrations of the aqueous extract and 3 mg
disc-1 of the same extract reduced the growth of the same bacteria. Phytochemical
analysis of the different solvent extracted samples suggested the presence or
absence of various metabolites including alkaloids, saponins, tannins, sterols,
flavonoids, protein, carbohydrates and fats.
PMID- 29348088
TI - Prevalence of Hepatitis C virus and its risk factors in blood donors in district
Peshawar.
AB - The current study was designed in order to elucidate the most sensitive method
for daily practice as well as to evaluate the risk factors for HCV infection
associated with blood transfusion in District Peshawar. A total of 1400 healthy
volunteer blood donors were tested for Anti-HCV. A questionnaire was used to
evaluate the risk factors. Initial testing of all blood samples was done by
Immuno Chromatographic Technique (ICT) and confirmed by micro particle enzyme
immunoassay (MEIA) and Enzyme Linked Immunosorbent Assay (ELISA). The comparison
among ICT, ELISA and MEIA techniques was also evaluated for the purpose of
sensitivity. Among 1400 blood donors, 26 (1.85%) cases were found positive for
Anti-HCV. These 26 cases were positive on MEIA, 16 individuals were positive on
ELISA while 14 were positive on ICT. These 26 cases had different histories of
dental treatment (50%), traveled abroad (23.07%), surgery (11.53%), blood
transfusion (7.69%) and unknown reason (7.69%). Among all these different
histories of dental treatment and blood transfusion were the main risk factors
for HCV infection. The results revealed that MEIA is a quick and reliable
technique for routine screening of blood donors particularly for controlling the
spread of HCV.
PMID- 29348089
TI - A study of serological markers and lipid profile in non-alcoholic liver cirrhosis
patients.
AB - Cirrhosis is the end result of chronic liver damage, associated with altered
serum biomarkers and lipid profile. However, only few studies regarding serum
biomarkers and plasma lipid profile in non-alcoholic liver cirrhosis subjects
have been undertaken in Pakistan. This study aimed to evaluate the degree of
alterations of tumor markers and lipid profile in liver cirrhosis patients and in
normal healthy individuals. Levels of serological markers and plasma lipid
pattern was measured in liver cirrhosis patients and in sex and age matched
normal healthy individuals (n=46). Tumor marker alpha-fetoprotein (AFP) was
measured by ELISA, whereas plasma lipid profile and biomarker alanine aminotr
ansferase (ALT) was determined by colorimetric assays. In patients with cirrhosis
significant increase was observed in serum AFP and ALT levels when compared with
healthy individuals (p<0.05).The triglyceride levels were found to be
significantly higher, while LDL-C was significantly lower (p<0.05) in liver
cirrhosis patients. There was no significant difference in the plasma
concentration of cholesterol, total lipids and HDL-C in liver cirrhosis patients
as compared with normal individuals. AFP and ALT are useful markers in the
diagnosis of cirrhosis and can be used for the detection of hepatocellular
carcinoma (HCC) in cirrhosis patients. The assessment of plasma lipids and
lipoprotein pattern is also important for prognostic evaluation of patients with
cirrhosis.
PMID- 29348090
TI - Pharmacological validation of the folkloric uses of Cyperus rotundus L. in
different ailments: An in vivo and in vitro research.
AB - In vivo and in vitro research study was conducted on Cyperus rotundus to evaluate
the sound mechanistic background in the treatment of gastrointestinal, bronchial
and vascular disorders as well as in pain, emesis, pyrexia and bacterial
infections. Results showed that crude extract of Cyperus rotundus (Cr.Cr)
exhibited the dose-dependent spasmolytic effect in rabbit jejunum by inhibiting
the spontaneous and K+ (80 mM)-induced contractions. Pretreatment of tissue with
Cr. Cr caused the rightward shift of calcium concentration response curves,
similar to verapamil. Cr. Cr also caused the relaxation of K+(80 mM)- and
carbachol (1 uM)-induced contractions of trachea preparations, similar to that of
verapamil. Moreover, Cr. Cr also relaxed the contraction induced by the K+ (80
mM) and phenylephrine (1 uM) of aorta preparations. Data show that C. rotundus
possess the spasmolytic, bronchodilator and vasodilator activities possibly
through calcium channels blockade; validating its folkloric use in diarrhea,
dyspepsia, bronchitis, asthma and hypertension in addition to antibacterial,
antiemetic, antipyretic and analgesic activities.
PMID- 29348091
TI - Synthesis and antibacterial activity of the sulfonamide based schiff base and its
transition metal (II) complexes.
AB - A Schiff base 3 has been synthesized by equimolar reaction (condensation) of
sulfonamide i.e. sulfamethoxypyridazine 1 and substituted aromatic aldehyde i.e.
2-Hydroxy-1-Napthalene aldehyde 2. The synthesized Schiff base 3 and its Metal
(II) complexes were characterized by its physical, analytical (CHN analysis) and
spectral (UV & IR) analysis. The Staphylococcus aureus and Escherichia coli
bacterial strains were used for antibacterial activity of Sulfamethoxypyridazine
1, its Schiff base 3 and its transition metal (II) complexes 4-8. All of them
showed varied levels of activity.
PMID- 29348092
TI - Prescribing pattern of angiotensin receptor blocker: A study of errors and drug
drug interactions.
AB - Prescriptions comprising multi-drug therapy mostly illustrate the prescribing
error. The phenomenon of error is bonded with human inaccuracy. The erroneous
practice is observed in under developed countries like Pakistan, Bangladesh and
also in developed ones. Consequently drug-drug interaction is one of the most
common error associated with potentially serious adverse response even death.
Accordingly the present study was conducted to assess the prevalence of
prescribing errors and drug-drug interactions in out-patients receiving
angiotensin receptor blockers. The study was done with population size one
hundred fifty prescriptions obtained from different out-patient settings in
Karachi. The prescriptions were screened for prescribing errors and risk factors
for drug-drug interactions. Drug-drug interactions were recognized by
Micromedex.2.0.Drug-Reax(r)database. The most common type of error was omission
error. These errors were patient's age, weight and diagnosis found in 51.3%,
97.3% and 74% of prescriptions, respectively. The prevalence of drug-drug
interaction was 38%. A total of 746 drugs were prescribed with an average of 5
drugs per prescription and 450 medication errors were detected. Majority of the
interaction were moderate (19.33%), others were minor (14%) and major (6%) in
severity. Patients who prescribed many drugs (more than 5 drugs in a while) had a
higher risk of developing drug-drug interactions (OR=4.76; 95% CI=2.30-9.64;
p=0.0001*).The study data reports the occurrence of prescribing errors in Karachi
and also necessitate the need of clinical pharmacist's services in health care
system. The step will help to minimize the risk factors by having the drug
prescriptions reviewed by the pharmacists.
PMID- 29348093
TI - Antifungal and cytotoxic activities of selected medicinal plants from Malaysia.
AB - This study was conducted to investigate the antifungal potential and cytotoxicity
of selected medicinal plants from Malaysia. The extracts from the stem of Cissus
quadrangularis and the leaves of Asplenium nidus, Pereskia bleo, Persicaria
odorata and Sauropus androgynus were assayed against six fungi using p
iodonitrotetrazolium-based on colorimetric broth microdilution method. All the
plant extracts were found to be fungicidal against at least one type of fungus.
The strongest fungicidal activity (minimum fungicidal concentration=0.16 mg/mL)
were exhibited by the hexane extract of C. quadrangularis, the hexane,
chloroform, ethanol and methanol extracts of P. bleo, the hexane and ethyl
acetate extracts of P. odorata, and the water extract of A. nidus. In terms of
cytotoxicity on the African monkey kidney epithelial (Vero) cells, the chloroform
extract of P. odorata produced the lowest 50% cytotoxic concentration (100.3 +/-
4.2 MU g/mL). In contrast, none of the water extracts from the studied plants
caused significant toxicity on the cells. The water extract of A. nidus warrants
further investigation since it showed the strongest fungicidal activity and the
highest total activity (179.22 L/g) against Issatchenkia orientalis, and did not
cause any toxicity to the Vero cells.
PMID- 29348094
TI - In vitro Salmonella typhi biofilm formation on gallstones and its disruption by
Manuka honey.
AB - Biofilm is a complex community of single or different types of microorganisms
(bacteria, viruses, fungi, protozoa) attached to a surface and stick to each
other through production of extracellular matrix. Salmonella typhi forms biofilm
on cholesterol gallstones resulting in carrier state. Once formed, biofilm is
difficult to treat. To date cholecystectomy is the only cure for this condition.
Manuka honey is known to have tremendous antibiofilm activity against various
organisms. S. typhi biofilm was grown in vitro on clinical samples of human
cholesterol gallstones by Gallstone tube assay method for 12 days. Biofilm mass
was quantified on day 1, 5, 7, 9 and 12 by crystal violet assay and was also
examined by scanning electron microscope. Three concentrations w/v of Manuka
honey (40%, 60% and 80%) were used, each one at 24, 48 and 72 hours. The most
effective concentration (80% w/v) was repeated on two sets of gallstones. Biofilm
mass was re quantified by crystal violet assay and was examined by scanning
electron microscope. S. typhi formed uniform biofilm on cholesterol gallstone
surface. The optical density measurements exhibited a rising pattern with time
thereby indicating an increase in biofilm mass. It was 0.2 on day 1 and 0.9 on
day 12. With 80% w/v Manuka honey, biofilm mass decreased most effectively with
0.5 OD after 72 hours. Biofilm formation by S, typhi on gallstones is surface
specific and bile dependant. Either increasing the duration (beyond 72 hours) of
the effective concentration (80% w/v) of honey or increasing the concentration
(above 80%) of honey for a specific duration (72 hour) may cause complete
disruption of the S. typhi biofilm on gallstone. S. typhi forms biofilm on
cholesterol gallstones surface in vitro and it can be visualized by scanning
electron microscopy. Biofilm mass can be quantified using crystal violet assay.
Among various concentrations 80% Manuka honey for 72 hours is most effective in
disrupting S. typhi biofilm on gallstones in vitro as evident from crystal violet
assay.
PMID- 29348095
TI - Estimation of simvastatin and cetirizine by RP-LC method: Application to freeze
and thaw (FT) stability studies.
AB - Sensitive, simple, reliable and rapid HPLC technique for the estimation of
simvastatin (SMV) and cetirizine has been designed in this study. The
chromatographic conditions were set using Shimadzu LC-10 AT VP pump, with UV
detector (SPD-10 AV-VP). System integration was performed with CBM-102 (Bus
Module). Partitioning of components was attained with pre-packed C-18 column of
Purospher Star (5 MUm, 250 x 4.6 mm) at ambient conditions. Injected volume of
sample was 10 MUl. Mobile phase was composed of 50:50 v/v ratio of
Acetonitrile/water (pH 3.0 adjusted with ortho-phosphoric acid) having 2
ml/minutes rate of flow. Compounds were detected in UV region at 225 nm. Percent
Recovery of simvastatin was observed in the range of 98-102%. All results were
found in accept table range of specification. The projected method is consistent,
specific, precise, and rapid, that can be employed to quantitate the SMV along
with cetirizine HCl. It was estimated by 3 successive cycles of freeze and thaw
stability. Results of FT samples were found within accept table limits the method
was developed and validated in raw materials, bulk formulations and final drug
products.
PMID- 29348096
TI - Antiulcer activity of methanol-chloroform extract of Channa striatus fillet.
AB - Channa striatus (Haruan) is Malaysian freshwater fish that is traditionally used
to treat ailments related to wound and also ulcers. The aimed of the present
study was to determine the mechanisms of anti-ulcer activity of chloroform:
methanol extract of C. striatus fillet (CMCS) in rats. The antiulcer profile of
CMCS, given orally in the doses of 50, 250 and 500mg/kg, was assessed using the
ethanol- and indomethacin-induced gastric ulcer models. The mechanisms of
antiulcer of CMCS were determined as follows; i) the antisecretory activity of
CMCS was measured using the pyloric ligation rat model, and; ii) the role of
nitric oxide (NO) and sulfhydryl compounds in the modulation of CMCS antiulcer
activity were determined by pre-treating the rats with L-NAME or NEM,
respectively, followed by the pre-treatment of rats with CMCS before subjecting
the animals to the ethanol-induced gastric ulcer model. From the results
obtained, CMCS exerted significant (P<0.05) antiulcer activity in both models of
gastric ulcer wherein the macroscopic and microscopic analysis of the stomach
supported the antiulcer claim. With regard to its antisecretory effect, CMCS did
not change the volume and pH, but reduce the total acidity only at the lower
doses of the gastric juice. Moreover, CMCS demonstrated antiulcer activity was
reversed by NEM, but not affected by L-NAME. In conclusion, CMCS shows antiulcer
activity that is modulated via its cytoprotective, but not antisecretory effect,
and in the presence of sulfhysryl compounds, but not NO.
PMID- 29348097
TI - A novel spectrophotometric determination of caroverine in pharmaceutical
formulations via derivatization with Folin-ciocalteu Phenol reagent.
AB - In this study we have reported a new, fast and extraction free spectrophotometric
procedure for the assessment of caroverine in pharmaceutical raw and tablet
dosage forms. In the reported visible spectrophotometric procedure tungstate in
Folin-Ciocalteu phenol reagent is reduced in alkaline medium and produces the
blue colored chromogen that shows Lambdamax at 740nm with the calibration range
of 2-28MUg/ml. The LOD and LOQ values are 1.15 and 3.81MUg/ml respectively. The
newly developed analytical procedure is used to determine caroverine in raw
material of and commercial tablets dosage forms. The spectrophotometric method
represented in this study is simple, rapid and extraction free. It may easily be
utilized for the determination of caroverine in pharmaceutical laboratories for
quality control and stability studies purpose.
PMID- 29348098
TI - Safety of fenbendazole in common peafowl (Pavo cristatus).
AB - The present study was undertaken to find out the safety levels of fenbendazole in
common peafowl. This bird, raised on aviaries and zoos, can be severely
parasitized with Ascaridia galli (enteric worms) and Syngamus trachea (gapeworm)
along with other parasitic worms. Fenbendazole is a highly effective
benzimidazole-class anthelmintic in animals. The objective of this work was to
provide target animal safety data in young peafowl and to demonstrate
reproductive safety in adult birds. During the experimental study, diets
containing fenbendazole at 0, 100, 200 and 300 ppm were fed for 21 days (three
times the normal treatment duration). Data for feed consumption, feed conversion
rate, and body weights were recorded for each bird in each group. Drug
concentrations in different tissues of birds were determined to correlate
concentrations with clinical observations, clinical pathology, and histologic
findings. There were no morbidities or mortalities after study day 21.
Additionally, there were no statistically significant treatment-related
differences among above mentioned parameters. Analysis of fenbendazole
concentrations in kidney, liver, leg/thigh, and breast muscle and skin with
associated fat revealed that, even at the highest dose level used and with no
feed withdrawal, fenbendazole concentrations were relatively low in these
tissues. These findings indicate that fenbendazole has a relatively wide margin
of safety in young peafowl and that the proposed dose of 100 ppm in the feed for
7 consecutive days is well within the margin of safety. In the reproductive
safety study, five breeder peafowl farms fed fendbendazole at 100ppm for 7 days
and collected data on hatching percentage of peahen eggs before and after
treatment. Reproductive performance in peahen was not adversely affected.
PMID- 29348099
TI - Spray-dried curcumin nanoemulsion: A new road to improvement of oral
bioavailability of curcumin.
AB - In this study a new soluble solid curcumin nanoemulsion powder was prepared using
spray-drying technology to improve the solubility and bioavailability of
curcumin. The liquid nanoemulsion consisted of curcumin, Capryol 90, Transcutol
P, and Cremophor RH40. The solid nanoemulsion was prepared by spray-drying the
liquid nanoemulsion in laboratory spray dryer, using lactose as solid carrier.
The in vitro release from powder formulation was 97.6% within 15 min while the
release from the curcumin crystalline was about 10%. An oral pharmacokinetic
study was conducted in rats and the relative bioavailability of spray-dried
curcumin powder significantly increased compared with that of curcumin
crystalline. The Cmax value of solid curcumin nanoemulsion powder was 5.5-fold
greater than the value of the curcumin crystalline in aqueous suspension. The
absorption mechanism of the spray-dried curcumin powders was discussed. The
results indicate that spray-drying in combination with nanoemulsion was a
powerful methodology for improving the dissolution rate and oral bioavailability
of curcumin.
PMID- 29348100
TI - Rapid diagnostic method of tobacco products in saliva by fourier transform
infrared spectroscopy (FTIR).
AB - The present study was designed to explore the easy and fast method diagnosis of
tobacco products in saliva of tobacco users (TU) by FTIR. Sixty four male tobacco
users (TU) with mean age range 15.3 to 30.7 years were randomly selected for
collection of saliva samples before and after tobacco use (smoking, chewing and
dipping tobacco). Twenty were the smoking tobacco users (STU), 24 were chewing
tobacco users (CTU) and 20 were dipping tobacco users (DTU). CTU were the users
of Mainpuri (n=10) and users of PEN, FIT, 2100 (n=14). Forty eight saliva samples
of age and gender matched healthy individuals with negative personal or family
history of any addiction were also collected for comparison which served as
controls. All were analyzed for their salivary flow rate, salivary pH and
salivary diagnostic bands by FTIR. Significantly increased SFR (p<0.05) and
salivary pH were found in after chewing tobacco as compared to before its
chewing. The comparison between after tobacco use and controls we found decreased
SFR and salivary pH for STU. Significant decreased SFR and increased salivary pH
were found before or after use of dipping tobacco as compared to controls. Sharp
bands at 735-745 cm-1 were found and may be used as salivary diagnostic bands for
STU, 945-949 cm-1 for DTU and 900-915 cm-1 for CTU as well as DTU. In conclusion,
the salivary diagnostic bands were found at 735-745 cm-1, 900-915 cm-1 and 945
949 cm-1 for TU by easy and fast method using FTIR.
PMID- 29348101
TI - Effects of gamma irradiation on the physico-chemical and biological properties of
levofloxacin.
AB - The aim of the present study was to examine the effect of gamma radiation on
levofloxacin. Powder form of levofloxacin was subjected to different radiation
doses (25, 50, 75, 100 and 125kGy) of Cobalt-60 source in a Gammacell-220 at a
rate of 8.5 Gray/hr. The effect of radiation has been investigated with the aid
of different spectroscopic techniques (UV-Vis, FT-IR), scanning electron
microscopy (SEM), X-ray diffraction (XRD), and by antibacterial activities. UV
data did not reveal significant changes in the structure of levofloxacin which is
supported by scanning electron microscopy. However, X-rays diffraction shows a
change in crystallinity of levofloxacin to an amorphous structure and this has
been reflected on the morphology of this compound as indicated by SEM images. The
antibacterial activities, on the other hand, reveal resistance of irradiated
levofloxacin against bacteria, where some bacteria were highly affected by the
irradiated drug. Similarly, FT-IR data show some changes in the functional groups
principal absorption bands, in the IR spectrum, at frequencies 3286, 2846, 1716
and 1620 cm-1 for the O-H stretching band of quinolone, C-H stretching band, and
C=O stretching band of carboxylic and pyridine. In addition, new peaks appeared
which were not seen in the non-irradiated spectrum. In conclusion, some changes
occurred in levofloxacin drug with the passage of radiation but the drug was
chemically stable.
PMID- 29348102
TI - Phytochemical screening and antibacterial activity of Cyclamen persicum Mill
tuber extracts.
AB - The emerging drug resistance bacteria increased the demand on the discovery of
antibiotics from natural sources. This research was aimed to study the
antibacterial reactivity; as well as the phytochemicals, of the wild type of
Cyclamen persicum, using nine different extraction methods where four solvents
(Methanol, Ethanol, Hexane; and Water) were involved with varied extraction
periods ranged from 2 up to 10 hours. The antibacterial activity of crude
methanol extract (CME) was found as the best method of extraction, with
particular emphasis on the method with prolonged extraction time of (10 hrs). The
antibacterial activities of produced CME were determined by using agar diffusion
method against two of gram-positive bacteria and two gram-negative ones. The CME
treated Mueller-Hinton-Agar plates, were exhibited antibacterial effects against
the gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis) by
showing of inhibition zone after overnight incubation, while nothing was noticed
on those of gram negative ones (Pseudomonas aeruginosa and Escherichia coli).
These results that proved the antibacterial activity of the Cyclamen persicum
tubers were positively tested the Saponin glycosides from plant. In addition to
that, methanol solvent could be the useful method for extractions of Cyclamen and
can be used in any developing drugs against pathogenic gram positive bacteria.
PMID- 29348103
TI - Prevalence of non alcoholic fatty liver and Non alcoholic Steatohepatitis in
Peshawar Cantonment, Khyber Pakhtunkhwa, Pakistan.
AB - Non-alcoholic fatty liver disease prevalence has not been well established. The
aims of this study was to define prospectively non-alcoholic steatohepatitis
(NASH) and non-alcoholic fatty liver disease (NAFLD) prevalence in hospitalized
and ambulatory patients 20-65 years old during June 2013 to June 2014 were
selected from Combined Military Hospital Peshawar Cantonment area. A base line
questionnaire and right upper quadrant ultrasound was completed by all patients.
On identifications of fatty liver among the selected cases further lab test data
and liver biopsy reports were obtained. Mean BMI of female was 29.9 + 5.65 while
prevalence of hypertension and diabetes was 49.8% and 16.6% respectively. Among
all patients 62% were Punjabies, 23% were Pathans while 12% were Sindhies.
Overall NAFLD prevalence was 47% while NASH was confirmed in 20 patients (12.3%
of total and 30%of ultrasound positive patients). Pathans had the highest
prevalence of NAFLD (58.5%) as compared to Punjabies (44.5%) and Sindhies
(35.3%). Pathans also had a higher prevalence of NASH compared with Punjabies
(19.5% VS 10%: P= 0.03). In general, NAFLD patients were more prevalent among
male (59%), Diabetic (P<0.00005), hypertensive (P<0.00005) and older (P =0.005).
They consumed more fast food (P=.049) had a higher BMI (P<0.0005) and had little
or no exercise as compared to their normal or non NAFLD counter parts (P=0.02).
NAFLD was found in 75% and NASH in 22.5% among the 26 diabetic patients. ALT,
AST, BMI, insulin, quantitative insulin sensitivity checks index and cytokeratin
18 correlated with NASH. It was concluded that NAFLD and NASH prevalence is
higher than estimated previously, Pathans and Patients with diabetes are at high
risk.
PMID- 29348104
TI - Disposition kinetics of omeprazole in healthy female volunteers in Faisalabad.
AB - Omeprazole (OMP) a proton pump inhibitor is widely used to suppress gastric acid
secretions of parietal cells of stomach and metabolized predominantly by CYP2C19.
The objective of the present study was to investigate the pharmacokinetics and
dosage regimen of OMP, after its single oral administration in eight healthy
adult female subjects. Blood samples were collected at different time intervals
after oral administration and their pH was measured. Plasma concentration of OMP
was determined by high performance liquid chromatography (HPLC) system equipped
with UV-visible Detector. The concentration versus time data was used to compute
the pharmacokinetic parameters with the help of computer software programme
MW/PHRAM APO version 3.02.Peak plasma concentration was (Cmax) 0.38+/-0.04 MUg/ml
achieved at 2.07+/-0.22 hrs. The elimination half-life (t1/2 beta) was1.82 +/-
0.42 hrs. Volume of distribution (Vd) in the present study was 0.40 +/- 0.07 l/kg
with total body clearance (ClB) 0.19 +/- 0.02 l/hr/kg and area under the curve
(AUC) 1.89 +/- 0.23 MUg.hr/ml.The pharmacokinetic properties which are different
from the literature after oral administration of 20 mg OMP in eight healthy
female volunteers may be due to the variations of environment and genetic
variation between Pakistan and drug manufacturing of foreign countries.
PMID- 29348105
TI - Report: Preparation of levodopa/carbidopa compound drug resins.
AB - The main objective of this study was to prepare the levodopa/carbidopa compound
drug resins and investigate affecting factors such as drug concentration,
temperature, particle size. The drug resins were made by bath method and the
effects of above factors during the process of preparation was studied. Studies
on the stabilities of drugs and drug resins were carried out by HPLC. The Results
showed that the preparation of drug resins was influenced by drug concentration,
resin particle size, reaction temperature and solvent concentration. In certain
conditions the degradation peaks were found in the chromatograms of levodopa and
carbidopa while the drug-resins remained undegraded. The study indicates that the
drug resin technology is an effective way of improving stability of the drug and
possesses certain sustained-release effects.
PMID- 29348106
TI - Report: Palladium glutathione, N-acetylcysteine, D-penicillamine conjugation
chemistry.
AB - The metalloelement Palladium has a number of potential Pharmaco-clinical
advantages. Palladium compounds have antiviral, antibacterial, neuroprotective
and antitumor properties. However studies have also indicated some mild to
serious toxic effects of Palladium metalloelements. Biothiols are important
antioxidants that provide protection against metals toxicity. The interaction of
metalloelements with biothiols can provide valuable information about the level
of toxicity of the metalloelements and about the protective role of biothiols
thereof. In this piece of work the effect of salt and complexes of Palladium on
the status of different thiols (GSH, NAC, and D-Pen) in aqueous medium, were
examined, The thiol quantification was carried out using Elman's method through
UV-visible spectrophotometry and 1H- NMR. Results of the study performed in
aqueous medium showed that level of different thiols depleted after the addition
of the inorganic salts and organic complexes of Palladium. The mechanism of
interaction of Palladium with thiols was examined using H-NMR. The results
indicate that the depletion in the level of thiols may be due to 1:1 or 1:2
conjugation of Palladium with thiols. These conjugation reactions further suggest
that the Palladium have xenobiotic nature causing oxidative stress and thiols
play their role in detoxification and biotransformation of these metalloelements.
PMID- 29348107
TI - Report: Regional variation in the chemical composition and antioxidant activity
of Rosmarinus officinalis L. from China and the Mediterranean region.
AB - Rosemary is an aromatic evergreen shrubby herb that is native to the
Mediterranean region. This herb is now widely cultivated in many regions of the
world. Rosemary is widely used in traditional Chinese medicines, foods,
nutraceuticals and cosmetics. Hydro distilled essential oils, obtained from
rosemary in China and the Mediterranean region, were analysed by gas
chromatography-mass spectrometry (GC-MS). Thirty-seven compounds accounting for
94.97%-99.72% of the oils were identified. The majority of the compounds in the
essential oils exhibited no significant differences (table 1 and fig. 1). The
extracts were prepared with three solvents of different polarity
(dichloromethane, ethyl acetate and aqueous). The ethyl acetate fractions
exhibited the highest phenol content and were found to be significantly more
active than the dichloromethane and aqueous fractions (fig. 2). Antioxidant
activity (by DPPH radical scavenging, ferric ion reduction (FRAP) and
thiobarbituric acid reactive substance (TBARS)) was also assessed. The ethyl
acetate extracts of Yunnan had the highest amount of antioxidant capacity from
China by DPPH and TBARS, with the lowest IC50 values being 0.0011 mg/ml, and
1.6611 mg/ml, respectively. In conclusion, the antioxidant activities of the
essential oils and ethyl acetate extracts from rosemary obtained by three
different testing methods revealed higher antioxidant activity from rosemary
grown in China than in the Mediterranean region. These results suggested that
Chinese rosemary should be widely used in food, traditional medicine, cosmetics
and perfume products, as well as other chemical industries.
PMID- 29348108
TI - Report: Fast chromatographic screening method for 7 drugs of potential threat in
drug facilitated crimes.
AB - In cases where pharmaceuticals and pharmaceutical candidates are involved in drug
facilitated crimes (DFC), like organ theft, robbery, rape and suicides, the
analysis of drug powders or solution residues found in crime scenes may give idea
on what the victims have ingested. An easy and fast simultaneous determination of
7 drugs; GHB (gamma-hydroxybutyrate), GBL (gamma-butyrolactone), norketamine,
ketamine, fenobarbital, fenitoin and thiopental which have the potential to be
used in DFC was performed. The method required no sample preparation and has 12
minutes elution time with a good chromatographic separation. The separation was
carried out on a C18 monolithic column with UV detection at 215 and 237nm. All r2
values were >=0.99 and the linear ranges were between 0.9956-1.0000. The LOD and
LOQ values were between 0.56-5.55MUgmL-1 and 1.69-16.82MUgmL-1 respectively. The
repeatability values were <7.35%. This is the first study in the simultaneous
screening of the above mentioned drugs using HPLC.
PMID- 29348109
TI - Review: Beyond conventional therapies: Complementary and alternative medicine in
the management of hypertension: An evidence-based review.
AB - Hypertension is one of the major causes of morbidity and mortality. Worldwide,
Hypertension is estimated to cause 7.5 million deaths, about 12.8% of the total
of all deaths. This accounts for 57 million disability adjusted life years
(DALYS) or 3.7% of total DALYS. This led WHO to set a target of 25% reduction in
prevalence by 2025. To reach that, WHO has adopted non-conventional methods for
the management of hypertension? Despite worldwide popularity of such non
conventional therapies, only small volume of evidence exists that supports its
effectiveness. This review attempted to make a critical appraisal of the
evidence, with the aim to (1) describe the therapeutic modalities frequently
used, and (2) review the current level of evidence attributable to each modality.
Databases from Cochrane Library, MEDLINE, PUBMED, and EMBASE were searched from
2005-2015. A total of 23 publications have been identified and selected. Out of
these, 15 systematic reviews and/or meta-analysis of RCTs, 5 RCTs, 1 non-RCT, and
2 observational studies without control. Among those 23 publications, therapeutic
modalities identified are: fish oil, qigong, yoga, coenzyme Q10, melatonin,
meditation, vitamin D, vitamin C, monounsaturated fatty acids, dietary amino
acids, chiropractic, osteopathy, folate, inorganic nitrate, beetroot juice,
beetroot bread, magnesium, and L-arginine. The followings were found to have weak
or no evidence: fish oil, yoga, vitamin D, monounsaturated fatty acid, dietary
amino-acids, and osteopathy. Those found to have significant reduction in blood
pressure are: magnesium, qigong, melatonin, meditation, vitamin C, chiropractic,
folate, inorganic nitrate, beetroot juice and L-arginine. Coenzyme Q10on the
other hand, showed contradicting results were some studies found weak or no
effect on blood pressure while others showed significant blood pressure reduction
effect. By virtue of the research designs and methodologies, the evidence
contributed from these studies is at level 1. Results from this review suggest
that certain non-conventional therapies may be effective in treating hypertension
and improving cardiac function and therefore considered as part of an evidence
based approach.
PMID- 29348110
TI - The Role of Ethnicity and Environment in the Regulation of Response to Sensory
Stimulus in Children: Protocol and Pilot Findings of a Neurophysiological Study.
AB - BACKGROUND: The ability to regulate the response to sensory stimuli has been
associated with successful behavioral patterns necessary for daily activities.
However, it is not known whether a child's ethnicity and environment can
influence autonomic regulatory mechanisms. OBJECTIVE: This study aims to explore
the role of ethnicity and environment in the regulation of responses to sensory
stimuli in children. METHODS: In this study, we intend to recruit 128 children
from different ethnic groups or environment contexts as follows: (1) 32 typically
developing Chinese children living in Hong Kong; (2) 32 typically developing
Filipino children living in Hong Kong; (3) 32 typically developing Filipino
children who are living in urban areas; and (4) 32 typically developing Filipino
children who are living in rural areas in Philippines. Autonomic activity (heart
rate variability [HRV] and electrodermal activity [EDA]) will be measured and
recorded using Polar H2 heart rate monitor and eSense GSR skin response sensor.
Autonomic activity (HRV-low frequency, HRV-high frequency, and EDA) at different
conditions between pairwise groupings will be tested using multivariate analysis
of variance (MANOVA). All significant levels will be set at P <=.05. RESULTS: We
present the research protocol of this study, as well as a short discussion of the
preliminary findings from our pilot data, with consequent power and sample size
analysis that informs the appropriate sample needed to test our hypothesis.
CONCLUSIONS: This study will increase the understanding on the role of individual
differences related to a child's ethnicity and environment in the regulation of
response to sensory stimuli. The findings of this research may further shed light
on the evaluation and treatment planning for children across and within cultures.
PMID- 29348111
TI - Leveraging Social Networking Sites for an Autoimmune Hepatitis Genetic
Repository: Pilot Study to Evaluate Feasibility.
AB - BACKGROUND: Conventional approaches to participant recruitment are often
inadequate in rare disease investigation. Social networking sites such as
Facebook may provide a vehicle to circumvent common research limitations and
pitfalls. We report our preliminary experience with Facebook-based methodology
for participant recruitment and participation into an ongoing study of autoimmune
hepatitis (AIH). OBJECTIVE: The goal of our research was to conduct a pilot study
to assess whether a Facebook-based methodology is capable of recruiting
geographically widespread participants into AIH patient-oriented research and
obtaining quality phenotypic data. METHODS: We established a Facebook community,
the Autoimmune Hepatitis Research Network (AHRN), in 2014 to provide a secure and
reputable distillation of current literature and AIH research opportunities.
Quarterly advertisements for our ongoing observational AIH study were posted on
the AHRN over 2 years. Interested and self-reported AIH participants were
subsequently enrolled after review of study materials and completion of an
informed consent by our study coordinator. Participants returned completed study
materials, including epidemiologic questionnaires and genetic material, to our
facility via mail. Outside medical records were obtained and reviewed by a study
physician. RESULTS: We successfully obtained all study materials from 29
participants with self-reported AIH within 2 years from 20 different states.
Liver biopsy results were available for 90% (26/29) of participants, of which 81%
(21/29) had findings consistent with AIH, 15% (4/29) were suggestive of AIH with
features of primary biliary cholangitis (PBC), and 4% (1/29) had PBC alone. A
total of 83% (24/29) had at least 2 of 3 proposed criteria: positive autoimmune
markers, consistent histologic findings of AIH on liver biopsy, and reported
treatment with immunosuppressant medications. Self-reported and physician records
were discrepant for immunosuppressant medications or for AIH/PBC diagnoses in 4
patients. CONCLUSIONS: Facebook can be an effective ancillary tool for
facilitating patient-oriented research in rare diseases. A social media-based
approach transcends established limitations in rare disease research and can
further develop research communities.
PMID- 29348112
TI - Comparing Short Dental Implants to Standard Dental Implants: Protocol for a
Systematic Review.
AB - BACKGROUND: Short dental implants have been proposed as a simpler, cheaper, and
faster alternative for the rehabilitation of atrophic edentulous areas to avoid
the disadvantages of surgical techniques for increasing bone volume. OBJECTIVE:
This review will compare short implants (4 to 8 mm) to standard implants (larger
than 8 mm) in edentulous jaws, evaluating on the basis of marginal bone loss
(MBL), survival rate, complications, and prosthesis failure. METHODS: We will
electronically search for randomized controlled trials comparing short dental
implants to standard dental implants in the following databases: PubMed, Web of
Science, EMBASE, Scopus, the Cochrane Central Register of Controlled Trials, and
ClinicalTrials.gov with English language restrictions. We will manually search
the reference lists of relevant reviews and the included articles in this review.
The following journals will also be searched: European Journal of Oral
Implantology, Clinical Oral Implants Research, and Clinical Implant Dentistry and
Related Research. Two reviewers will independently perform the study selection,
data extraction and quality assessment (using the Cochrane Collaboration tool) of
included studies. All meta-analysis procedures including appropriate effect size
combination, sub-group analysis, meta-regression, assessing publication or
reporting bias will be performed using Stata (Statacorp, TEXAS) version 12.1.
RESULTS: Short implant effectiveness will be assessed using the mean difference
of MBL in terms of weighted mean difference (WMD) and standardized mean
difference (SMD) using Cohen's method. The combined effect size measures in
addition to the related 95% confidence intervals will be estimated by a fixed
effect model. The heterogeneity of the related effect size will be assessed using
a Q Cochrane test and I2 measure. The MBL will be presented by a standardized
mean difference with a 95% confidence interval. The survival rate of implants,
prostheses failures, and complications will be reported using a risk ratio at 95%
confidence interval (P<.05). CONCLUSIONS: The present protocol illustrates an
appropriate method to perform the systematic review and ensures transparency for
the completed review. The results will be published in a peer-reviewed journal
and social networks. In addition, an ethics approval is not considered necessary.
TRIAL REGISTRATION: PROSPERO registration number: CRD42016048363;
https://www.crd.york.ac.uk/PROSPERO/ display_record.asp?ID=CRD42016048363
(Archived by WebCite at http://www.webcitation.org/6wZ7Fntry).
PMID- 29348113
TI - GENETICS IN ENDOCRINOLOGY: The expanding genetic horizon of primary
aldosteronism.
AB - Aldosterone is the main mineralocorticoid hormone in humans and plays a key role
in maintaining water and electrolyte homeostasis. Primary aldosteronism (PA),
characterized by autonomous aldosterone overproduction by the adrenal glands,
affects 6% of the general hypertensive population and can be either sporadic or
familial. Aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia
(BAH) are the two most frequent subtypes of sporadic PA and 4 forms of familial
hyperaldosteronism (FH-I to FH-IV) have been identified. Over the last six years,
the introduction of next-generation sequencing has significantly improved our
understanding of the molecular mechanisms responsible for autonomous aldosterone
overproduction in both sporadic and familial PA. Somatic mutations in four genes
(KCNJ5, ATP1A1, ATP2B3 and CACNA1D), differently implicated in intracellular ion
homeostasis, have been identified in nearly 60% of the sporadic APAs. Germline
mutations in KCNJ5 and CACNA1H cause FH-III and FH-IV, respectively, while
germline mutations in CACNA1D cause the rare PASNA syndrome, featuring primary
aldosteronism seizures and neurological abnormalities. Further studies are
warranted to identify the molecular mechanisms underlying BAH and FH-II, the most
common forms of sporadic and familial PA whose molecular basis is yet to be
uncovered.
PMID- 29348114
TI - Question 2: Is it safe to use the centre of the heel for obtaining capillary
blood samples in neonates?
PMID- 29348115
TI - Investigation of developmental delay.
PMID- 29348116
TI - Intensive care: because we can or because we should?
PMID- 29348117
TI - Graves' disease. Time to move on.
PMID- 29348118
TI - Targeted Deletion of Adipocyte Abca1 (ATP-Binding Cassette Transporter A1)
Impairs Diet-Induced Obesity.
AB - OBJECTIVE: Adipose tissue cholesterol increases with adipocyte triglyceride
content and size during development of obesity. However, how adipocyte
cholesterol affects adipocyte function is poorly understood. The aim of this
study was to evaluate the role of the cellular cholesterol exporter, Abca1 (ATP
binding cassette transporter A1), on adipose tissue function during diet-induced
obesity. APPROACH AND RESULTS: Adiponectin Cre recombinase transgenic mice were
crossed with Abca1flox/flox mice to generate ASKO (adipocyte-specific Abca1
knockout) mice. Control and ASKO mice were then fed a high-fat, high-cholesterol
(45% calories as fat and 0.2% cholesterol) diet for 16 weeks. Compared with
control mice, ASKO mice had a 2-fold increase in adipocyte plasma membrane
cholesterol content and significantly lower body weight, epididymal fat pad
weight, and adipocyte size. ASKO versus control adipose tissue had decreased
PPARgamma (peroxisome proliferator-activated receptor gamma) and CCAAT/enhancer
binding protein expression, nuclear SREBP1 (sterol regulatory element-binding
protein 1) protein, lipogenesis, and triglyceride accretion but similar Akt
activation after acute insulin stimulation. Acute siRNA-mediated Abca1 silencing
during 3T3L1 adipocyte differentiation reduced adipocyte Abca1 and PPARgamma
protein expression and triglyceride content. Systemic stimulated triglyceride
lipolysis and glucose homeostasis were similar between control and ASKO mice.
CONCLUSIONS: Adipocyte Abca1 is a key regulator of adipocyte lipogenesis and
lipid accretion, likely because of increased adipose tissue membrane cholesterol,
resulting in decreased activation of lipogenic transcription factors PPARgamma
and SREBP1.
PMID- 29348120
TI - APOC3 Loss-of-Function Mutations, Remnant Cholesterol, Low-Density Lipoprotein
Cholesterol, and Cardiovascular Risk: Mediation- and Meta-Analyses of 137 895
Individuals.
AB - OBJECTIVE: Loss-of-function mutations in APOC3 associate with low remnant
cholesterol levels and low risk of ischemic vascular disease (IVD). Because some
studies show an additional association with low levels of low-density lipoprotein
cholesterol (LDL-C), low LDL-C may explain the low risk of IVD in APOC3 loss-of
function heterozygotes. We tested to what extent the low risk of IVD in APOC3
loss-of-function heterozygotes is mediated by low plasma remnant cholesterol and
LDL-C. APPROACH AND RESULTS: In APOC3 loss-of-function heterozygotes versus
noncarriers, we first determined remnant cholesterol and LDL-C levels in meta
analyses of 137 895 individuals. Second, we determined whether the association
with LDL-C was masked by lipid-lowering therapy. Finally, using mediation
analysis, we determined the fraction of the low risk of IVD and ischemic heart
disease mediated by remnant cholesterol and LDL-C. In meta-analyses, remnant
cholesterol was 43% lower (95% confidence interval, 40%-47%), and LDL-C was 4%
lower (1%-6%) in loss-of-function heterozygotes (n=776) versus noncarriers. In
the general population, LDL-C was 3% lower in loss-of-function heterozygotes
versus noncarriers, 4% lower when correcting for lipid-lowering therapy, and 3%
lower in untreated individuals (P values, 0.06-0.008). Remnant cholesterol
mediated 37% of the observed 41% lower risk of IVD and 54% of the observed 36%
lower risk of ischemic heart disease; corresponding values mediated by LDL-C were
1% and 2%. CONCLUSIONS: The low risk of IVD observed in APOC3 loss-of-function
heterozygotes is mainly mediated by the associated low remnant cholesterol and
not by low LDL-C. Furthermore, the contribution of LDL-C to IVD risk was not
masked by lipid-lowering therapy. This suggests APOC3 and remnant cholesterol as
important new targets for reducing cardiovascular risk.
PMID- 29348119
TI - Cigarette Smoke Initiates Oxidative Stress-Induced Cellular Phenotypic Modulation
Leading to Cerebral Aneurysm Pathogenesis.
AB - OBJECTIVE: Cigarette smoke exposure (CSE) is a risk factor for cerebral aneurysm
(CA) formation, but the molecular mechanisms are unclear. Although CSE is known
to contribute to excess reactive oxygen species generation, the role of oxidative
stress on vascular smooth muscle cell (VSMC) phenotypic modulation and
pathogenesis of CAs is unknown. The goal of this study was to investigate whether
CSE activates a NOX (NADPH oxidase)-dependent pathway leading to VSMC phenotypic
modulation and CA formation and rupture. APPROACH AND RESULTS: In cultured
cerebral VSMCs, CSE increased expression of NOX1 and reactive oxygen species
which preceded upregulation of proinflammatory/matrix remodeling genes (MCP-1,
MMPs [matrix metalloproteinase], TNF-alpha, IL-1beta, NF-kappaB, KLF4 [Kruppel
like factor 4]) and downregulation of contractile genes (SM-alpha-actin [smooth
muscle alpha actin], SM-22alpha [smooth muscle 22alpha], SM-MHC [smooth muscle
myosin heavy chain]) and myocardin. Inhibition of reactive oxygen species
production and knockdown of NOX1 with siRNA or antisense decreased CSE-induced
upregulation of NOX1 and inflammatory genes and downregulation of VSMC
contractile genes and myocardin. p47phox-/- NOX knockout mice, or pretreatment
with the NOX inhibitor, apocynin, significantly decreased CA formation and
rupture compared with controls. NOX1 protein and mRNA expression were similar in
p47phox-/- mice and those pretreated with apocynin but were elevated in
unruptured and ruptured CAs. CSE increased CA formation and rupture, which was
diminished with apocynin pretreatment. Similarly, NOX1 protein and mRNA and
reactive oxygen species were elevated by CSE, and in unruptured and ruptured CAs.
CONCLUSIONS: CSE initiates oxidative stress-induced phenotypic modulation of
VSMCs and CA formation and rupture. These molecular changes implicate oxidative
stress in the pathogenesis of CAs and may provide a potential target for future
therapeutic strategies.
PMID- 29348122
TI - Macrophage Transitions in Heart Valve Development and Myxomatous Valve Disease.
AB - OBJECTIVE: Hematopoietic-derived cells have been reported in heart valves but
remain poorly characterized. Interestingly, recent studies reveal infiltration of
leukocytes and increased macrophages in human myxomatous mitral valves.
Nevertheless, timing and contribution of macrophages in normal valves and
myxomatous valve disease are still unknown. The objective is to characterize
leukocytes during postnatal heart valve maturation and identify macrophage
subsets in myxomatous valve disease. APPROACH AND RESULTS: Leukocytes are
detected in heart valves after birth, and their numbers increase during postnatal
valve development. Flow cytometry and immunostaining analysis indicate that
almost all valve leukocytes are myeloid cells, consisting of at least 2
differentially localized macrophage subsets and dendritic cells. Beginning a week
after birth, increased numbers of CCR2+ (C-C chemokine receptor type 2)
macrophages are present, consistent with infiltrating populations of monocytes,
and macrophages are localized in regions of biomechanical stress in the valve
leaflets. Valve leukocytes maintain expression of CD (cluster of differentiation)
45 and do not contribute to significant numbers of endothelial or interstitial
cells. Macrophage lineages were examined in aortic and mitral valves of Axin2 KO
(knockout) mice that exhibit myxomatous features. Infiltrating CCR2+ monocytes
and expansion of CD206-expressing macrophages are localized in regions where
modified heavy chain hyaluronan is observed in myxomatous valve leaflets. Similar
colocalization of modified hyaluronan and increased numbers of macrophages were
observed in human myxomatous valve disease. CONCLUSIONS: Our study demonstrates
the heterogeneity of myeloid cells in heart valves and highlights an alteration
of macrophage subpopulations, notably an increased presence of infiltrating CCR2+
monocytes and CD206+ macrophages, in myxomatous valve disease.
PMID- 29348121
TI - Endothelial Cell-Derived Von Willebrand Factor, But Not Platelet-Derived,
Promotes Atherosclerosis in Apolipoprotein E-Deficient Mice.
AB - OBJECTIVE: VWF (von Willebrand factor) is synthesized by endothelial cells and
megakaryocytes and is known to contribute to atherosclerosis. In vitro studies
suggest that platelet-derived VWF (Plt-VWF) is biochemically and functionally
different from endothelial cell-derived VWF (EC-VWF). We determined the role of
different pools of VWF in the pathophysiology of atherosclerosis. APPROACH AND
RESULTS: Using bone marrow transplantation, we generated chimeric Plt-VWF, EC
VWF, and Plt-VWF mice lacking a disintegrin and metalloprotease with
thrombospondin type I repeats-13 in platelets and plasma on apolipoprotein E
deficient (Apoe-/-) background. Controls were chimeric Apoe-/- mice transplanted
with bone marrow from Apoe-/- mice (wild type) and Vwf-/-Apoe-/- mice
transplanted with bone marrow from Vwf-/-Apoe-/- mice (VWF-knock out).
Susceptibility to atherosclerosis was evaluated in whole aortae and cross
sections of the aortic sinus in female mice fed a high-fat Western diet for 14
weeks. VWF-knock out, Plt-VWF, and Plt-VWF mice lacking a disintegrin and
metalloprotease with thrombospondin type I repeats-13 exhibited reduced plaque
size characterized by smaller necrotic cores, reduced neutrophil and
monocytes/macrophages content, decreased MMP9 (matrix metalloproteinase), MMP2,
and CX3CL1 (chemokine [C-X3-C motif] ligand 1)-positive area, and abundant
interstitial collagen (P<0.05 versus wild-type or EC-VWF mice). Atherosclerotic
lesion size and composition were comparable between wild-type or EC-VWF mice.
Together these findings suggest that EC-VWF, but not Plt-VWF, promotes
atherosclerosis exacerbation. Furthermore, intravital microscopy experiments
revealed that EC-VWF, but not Plt-VWF, contributes to platelet and leukocyte
adhesion under inflammatory conditions at the arterial shear rate. CONCLUSIONS:
EC-VWF, but not Plt-VWF, contributes to VWF-dependent atherosclerosis by
promoting platelet adhesion and vascular inflammation. Plt-VWF even in the
absence of a disintegrin and metalloprotease with thrombospondin type I repeats
13, both in platelet and plasma, was not sufficient to promote atherosclerosis.
PMID- 29348123
TI - Rash associated with rivaroxaban use.
AB - PURPOSE: A case of a patient who developed a hypersensitivity reaction to
rivaroxaban in the form of a diffuse, exanthematous rash is reported. SUMMARY:
After starting rivaroxaban for treatment of cancer-associated deep vein
thrombosis (DVT) with pulmonary embolism (PE), a 69-year-old Caucasian woman
arrived at an oncology clinic with a diffuse, exanthematous (morbilliform) rash
on her neck and torso, spreading to her upper and lower extremities. She reported
that the symptoms started to develop about 48 hours after transitioning from
subcutaneous enoxaparin to oral rivaroxaban. The patient's symptoms did not
subside with diphenhydramine 25-50 mg orally every 6-8 hours. The patient was
switched back to enoxaparin therapy for continued anticoagulation therapy. On day
5, rivaroxaban and diphenhydramine were discontinued. Oral dexamethasone 4 mg
twice daily was initiated, and the patient transitioned from rivaroxaban to
enoxaparin 1 mg/kg every 12 hours subcutaneously. On day 8, the rash had
diminished considerably and was present only on her thighs. Analysis of the case
using the adverse drug reaction probability scale of Naranjo et al. indicated
that rivaroxaban was the probable cause of the hypersensitivity reaction. Four
prior case reports of rivaroxaban hypersensitivity manifesting as a rash have
been previously reported, with this being the first in a female and the first in
a patient undergoing treatment of DVT and PE in the setting of active cancer.
CONCLUSION: A 69-year-old Caucasian woman developed a diffuse, exanthematous rash
on day 3 of rivaroxaban treatment. Symptoms abated after rivaroxaban
discontinuation and treatment with dexamethasone.
PMID- 29348124
TI - Organic Anion Transporting Polypeptide 1a4 is Responsible for the Hepatic Uptake
of Cardiac Glycosides in Mice.
AB - Among organic anion transporting polypeptide (Oatp) family transporters expressed
in the rodent liver, such as Oatp1a1, Oatp1a4, Oatp1b2, and Oatp2b1, Oatp1a4 has
a unique character to recognize neutral cardiac glycosides as a substrate in
addition to organic anions. The relative contribution of Oatp1a4 to the substrate
uptake into hepatocytes has not been clarified. In this study, we investigated
the importance of Oatp1a4 in the hepatic uptake of its substrate drugs using
Slco1a4-/- mice. The hepatic mRNA expression of Slco1a4 was decreased
significantly in Slco1a4-/- mice, whereas no differences were seen in other
hepatic transporters between wild-type and Slco1a4-/- mice. We determined the
plasma concentrations and liver-to-plasma concentration ratios (Kp,liver) of
Oatp1a4 substrates, including ouabain, digoxin, BQ-123, fexofenadine,
rosuvastatin, pravastatin, nafcillin, and telmisartan, after continuous
intravenous infusion. The plasma concentrations of ouabain and rosuvastatin were
2.1-fold and 1.7-fold higher in Slco1a4-/- mice, and Kp,liver of ouabain and
digoxin were 13.4-fold and 4.3-fold lower in Slco1a4-/- mice, respectively.
Furthermore, the biliary clearance of ouabain and digoxin with regard to plasma
concentration were 21.9-fold and 4.1-fold lower in Slco1a4-/- mice, respectively,
accompanied with a marked reduction in their Kp,liver, whereas the systemic
clearance of ouabain, but not digoxin, was reduced significantly in Slco1a4-/-
mice. These results suggest that Oatp1a4 plays a major role in the hepatic
accumulation of cardiac glycosides in mice.
PMID- 29348125
TI - Metabolism and Disposition of a Novel Selective alpha7 Neuronal Acetylcholine
Receptor Agonist ABT-126 in Humans: Characterization of the Major Roles for
Flavin-Containing Monooxygenases and UDP-Glucuronosyl Transferase 1A4 and 2B10 in
Catalysis.
AB - Mass balance, metabolism, and excretion of ABT-126, an alpha7 neuronal
acetylcholine receptor agonist, were characterized in healthy male subjects (n =
4) after a single 100-mg (100 MUCi) oral dose. The total recovery of the
administered radioactivity was 94.0% (+/-2.09%), with 81.5% (+/-10.2%) in urine
and 12.4% (+/-9.3%) in feces. Metabolite profiling indicated that ABT-126 had
been extensively metabolized, with 6.6% of the dose remaining as unchanged parent
drug in urine. Parent drug accounted for 12.2% of the administered radioactivity
in feces. The primary metabolic transformations of ABT-126 involved aza
adamantane N-oxidation (M1, 50.3% in urine) and aza-adamantane N-glucuronidation
(M11, 19.9% in urine). M1 and M11 were also major circulating metabolites,
accounting for 32.6% and 36.6% of the drug-related material in plasma,
respectively. These results demonstrated that ABT-126 is eliminated primarily by
hepatic metabolism, followed by urinary excretion. Enzymatic studies suggested
that M1 formation is mediated primarily by human liver flavin-containing
monooxygenase (FMO)3 and, to a lesser extent, by human kidney FMO1; M11 is
generated mainly by human uridine 5'-diphospho-glucuronosyltransferase (UGT) 1A4,
whereas UGT 2B10 also contributes to ABT-126 glucuronidation. Species-dependent
formation of M11 was observed in hepatocytes; M11 was formed in human and monkey
hepatocytes, but not in rat and dog hepatocytes, suggesting that monkeys
constitute an appropriate model for predicting the fate of compounds undergoing
significant N-glucuronidation. M1 and M11 are not expected to have clinically
relevant on- or off-target pharmacologic activities. In summary, this study
characterized ABT-126 metabolites in the circulation and excreta and the primary
elimination pathways of ABT-126 in humans.
PMID- 29348126
TI - Concerns about composite reference standards in diagnostic research.
PMID- 29348127
TI - Murine chronic graft-versus-host disease proteome profiling discovers CCL15 as a
novel biomarker in patients.
AB - Improved diagnostic and treatment methods are needed for chronic graft-versus
host disease (cGVHD), the leading cause of late nonrelapse mortality (NRM) in
long-term survivors of allogenic hematopoietic cell transplantation. Validated
biomarkers that facilitate disease diagnosis and classification generally are
lacking in cGVHD. Here, we conducted whole serum proteomics analysis of a well
established murine multiorgan system cGVHD model. We discovered 4 upregulated
proteins during cGVHD that are targetable by genetic ablation or blocking
antibodies, including the RAS and JUN kinase activator, CRKL, and CXCL7, CCL8,
and CCL9 chemokines. Donor T cells lacking CRK/CRKL prevented the generation of
cGVHD, germinal center reactions, and macrophage infiltration seen with wild-type
T cells. Whereas antibody blockade of CCL8 or CXCL7 was ineffective in treating
cGVHD, CCL9 blockade reversed cGVHD clinical manifestations, histopathological
changes, and immunopathological hallmarks. Mechanistically, elevated CCL9
expression was present predominantly in vascular smooth muscle cells and uniquely
seen in cGVHD mice. Plasma concentrations of CCL15, the human homolog of mouse
CCL9, were elevated in a previously published cohort of 211 cGVHD patients
compared with controls and associated with NRM. In a cohort of 792 patients,
CCL15 measured at day +100 could not predict cGVHD occurring within the next 3
months with clinically relevant sensitivity/specificity. Our findings demonstrate
for the first time the utility of preclinical proteomics screening to identify
potential new targets for cGVHD and specifically CCL15 as a diagnosis marker for
cGVHD. These data warrant prospective biomarker validation studies.
PMID- 29348129
TI - Genomic CDKN2A/2B deletions in adult Ph+ ALL are adverse despite allogeneic stem
cell transplantation.
AB - We investigated the role of copy number alterations to refine risk stratification
in adult Philadelphia chromosome positive (Ph)+ acute lymphoblastic leukemia
(ALL) treated with tyrosine kinase inhibitors (TKIs) and allogeneic stem cell
transplantation (aSCT). Ninety-seven Ph+ ALL patients (median age 41 years; range
18-64 years) within the prospective multicenter German Multicenter ALL Study
Group studies 06/99 (n = 8) and 07/2003 (n = 89) were analyzed. All patients
received TKI and aSCT in first complete remission (CR1). Copy number analysis was
performed with single nucleotide polymorphism arrays and validated by multiplex
ligation-dependent probe amplification. The frequencies of recurrently deleted
genes were: IKZF1, 76%; CDKN2A/2B, 45%; PAX5, 43%; BTG1, 18%; EBF1, 13%; ETV6,
5%; RB, 14%. In univariate analyses, the presence of CDKN2A/2B deletions had a
negative impact on all endpoints: overall survival (P = .023), disease-free
survival (P = .012), and remission duration (P = .036). The negative predictive
value of CDKN2A/2B deletions was retained in multivariable analysis along with
other factors such as timing of TKI therapy, intensity of conditioning, achieving
remission after induction phase 1 and BTG1 deletions. We therefore conclude that
acquired genomic CDKN2A/2B deletions identify a subgroup of Ph+ ALL patients, who
have an inferior prognosis despite aSCT in CR1. Their poor outcome was
attributable primarily to a high relapse rate after aSCT.
PMID- 29348128
TI - Pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, combined with
azacitidine in patients with AML.
AB - Pevonedistat (TAK-924/MLN4924) is a novel inhibitor of NEDD8-activating enzyme
(NAE) with single-agent activity in relapsed/refractory acute myeloid leukemia
(AML). We performed a phase 1b study of pevonedistat (PEV) with azacitidine (AZA)
based on synergistic activity seen preclinically. Primary objectives included
safety and tolerability, and secondary objectives included pharmacokinetics (PK)
and disease response. Patients >=60 years with treatment-naive AML (unfit for
standard induction therapy) received PEV 20 or 30 mg/m2 IV on days 1, 3, and 5
combined with fixed-dose AZA (75 mg/m2 IV/subcutaneously) on days 1 to 5, 8, and
9, every 28 days. The most common treatment-emergent adverse events were
constipation (48%), nausea (42%), fatigue (42%), and anemia (39%). In total, 11
deaths were observed and considered unrelated to study therapy by the
investigators. Transient elevations in aspartate aminotransferase (AST) and
alanine aminotransferase (ALT) were dose limiting. The recommended phase 2 dose
(RP2D) of PEV in this combination is 20 mg/m2 PEV PK was not altered by the
addition of AZA. Overall response rate (ORR) based on an intent-to-treat analysis
was 50% (20 complete remissions [CRs], 5 complete remission with incomplete
peripheral count recovery, 7 partial remissions [PRs]), with an 8.3-month median
duration of remission. In patients receiving >=6 cycles of therapy (n = 23, 44%),
ORR was 83%. In patients with TP53 mutations, the composite CR/PR rate was 80%
(4/5). Two of these patients stayed on study for >10 cycles. Baseline bone marrow
blast percentage or cytogenetic/molecular risk did not influence ORR. This study
was registered at www.clinicaltrials.gov as #NCT01814826.
PMID- 29348130
TI - SETD1A protects HSCs from activation-induced functional decline in vivo.
AB - The regenerative capacity of hematopoietic stem cells (HSCs) is limited by the
accumulation of DNA damage. Conditional mutagenesis of the histone 3 lysine 4
(H3K4) methyltransferase, Setd1a, revealed that it is required for the expression
of DNA damage recognition and repair pathways in HSCs. Specific deletion of
Setd1a in adult long-term (LT) HSCs is compatible with adult life and has little
effect on the maintenance of phenotypic LT-HSCs in the bone marrow. However,
SETD1A-deficient LT-HSCs lose their transcriptional cellular identity,
accompanied by loss of their proliferative capacity and stem cell function under
replicative stress in situ and after transplantation. In response to inflammatory
stimulation, SETD1A protects HSCs and progenitors from activation-induced
attrition in vivo. The comprehensive regulation of DNA damage responses by SETD1A
in HSCs is clearly distinct from the key roles played by other epigenetic
regulators, including the major leukemogenic H3K4 methyltransferase MLL1, or
MLL5, indicating that HSC identity and function is supported by cooperative
specificities within an epigenetic framework.
PMID- 29348131
TI - Iodine Extravasation Quantification on Dual-Energy CT of the Brain Performed
after Mechanical Thrombectomy for Acute Ischemic Stroke Can Predict Hemorrhagic
Complications.
AB - BACKGROUND AND PURPOSE: Intracerebral hemorrhage represents a potentially severe
complication of revascularization of acute ischemic stroke. The aim of our study
was to assess the capability of iodine extravasation quantification on dual
energy CT performed immediately after mechanical thrombectomy to predict
hemorrhagic complications. MATERIALS AND METHODS: Because this was a
retrospective study, the need for informed consent was waived. Eighty-five
consecutive patients who underwent brain dual-energy CT immediately after
mechanical thrombectomy for acute ischemic stroke between August 2013 and January
2017 were included. Two radiologists independently evaluated dual-energy CT
images for the presence of parenchymal hyperdensity, iodine extravasation, and
hemorrhage. Maximum iodine concentration was measured. Follow-up CT examinations
performed until patient discharge were reviewed for intracerebral hemorrhage
development. The correlation between dual-energy CT parameters and intracerebral
hemorrhage development was analyzed by the Mann-Whitney U test and Fisher exact
test. Receiver operating characteristic curves were generated for continuous
variables. RESULTS: Thirteen of 85 patients (15.3%) developed hemorrhage. On
postoperative dual-energy CT, parenchymal hyperdensities and iodine extravasation
were present in 100% of the patients who developed intracerebral hemorrhage and
in 56.3% of the patients who did not (P = .002 for both). Signs of bleeding were
present in 35.7% of the patients who developed intracerebral hemorrhage and in
none of the patients who did not (P < .001). Median maximum iodine concentration
was 2.63 mg/mL in the patients who developed intracerebral hemorrhage and 1.4
mg/mL in the patients who did not (P < .001). Maximum iodine concentration showed
an area under the curve of 0.89 for identifying patients developing intracerebral
hemorrhage. CONCLUSIONS: The presence of parenchymal hyperdensity with a maximum
iodine concentration of >1.35 mg/mL may identify patients developing
intracerebral hemorrhage with 100% sensitivity and 67.6% specificity.
PMID- 29348132
TI - T2 Relaxometry MRI Predicts Cerebral Palsy in Preterm Infants.
AB - BACKGROUND AND PURPOSE: T2-relaxometry brain MR imaging enables objective
measurement of brain maturation based on the water-macromolecule ratio in white
matter, but the outcome correlation is not established in preterm infants. Our
study aimed to predict neurodevelopment with T2-relaxation values of brain MR
imaging among preterm infants. MATERIALS AND METHODS: From January 1, 2012, to
May 31, 2015, preterm infants who underwent both T2-relaxometry brain MR imaging
and neurodevelopmental follow-up were retrospectively reviewed. T2-relaxation
values were measured over the periventricular white matter, including sections
through the frontal horns, midbody of the lateral ventricles, and centrum
semiovale. Periventricular T2 relaxometry in relation to corrected age was
analyzed with restricted cubic spline regression. Prediction of cerebral palsy
was examined with the receiver operating characteristic curve. RESULTS: Thirty
eight preterm infants were enrolled for analysis. Twenty patients (52.6%) had
neurodevelopmental abnormalities, including 8 (21%) with developmental delay
without cerebral palsy and 12 (31.6%) with cerebral palsy. The periventricular T2
relaxation values in relation to age were curvilinear in preterm infants with
normal development, linear in those with developmental delay without cerebral
palsy, and flat in those with cerebral palsy. When MR imaging was performed at >1
month corrected age, cerebral palsy could be predicted with T2 relaxometry of the
periventricular white matter on sections through the midbody of the lateral
ventricles (area under the receiver operating characteristic curve = 0.738;
cutoff value of >217.4 with 63.6% sensitivity and 100.0% specificity).
CONCLUSIONS: T2-relaxometry brain MR imaging could provide prognostic prediction
of neurodevelopmental outcomes in premature infants. Age-dependent and area
selective interpretation in preterm brains should be emphasized.
PMID- 29348133
TI - Review of the Imaging Features of Benign Osteoporotic and Malignant Vertebral
Compression Fractures.
AB - Vertebral compression fractures are very common, especially in the elderly.
Benign osteoporotic and malignant vertebral compression fractures have extremely
different management and prognostic implications. Although there is an overlap in
appearances, characteristic imaging features can aid in the distinction between
these 2 types of compression fractures. The aim of this review is to characterize
the imaging features of benign and malignant vertebral compression fractures seen
with CT, PET, SPECT, and MR imaging.
PMID- 29348134
TI - Cerebral Mitochondrial Microangiopathy Leads to Leukoencephalopathy in
Mitochondrial Neurogastrointestinal Encephalopathy.
AB - BACKGROUND AND PURPOSE: Mitochondrial neurogastrointestinal encephalopathy is a
rare disorder due to recessive mutations in the thymidine phosphorylase gene,
encoding thymidine phosphorylase protein required for mitochondrial DNA
replication. Clinical manifestations include gastrointestinal dysmotility and
diffuse asymptomatic leukoencephalopathy. This study aimed to elucidate the
mechanisms underlying brain leukoencephalopathy in patients with mitochondrial
neurogastrointestinal encephalopathy by correlating multimodal neuroradiologic
features to postmortem pathology. MATERIALS AND METHODS: Seven patients underwent
brain MR imaging, including single-voxel proton MR spectroscopy and diffusion
imaging. Absolute concentrations of metabolites calculated by acquiring
unsuppressed water spectra at multiple TEs, along with diffusion metrics based on
the tensor model, were compared with those of healthy controls using unpaired t
tests in multiple white matters regions. Brain postmortem histologic,
immunohistochemical, and molecular analyses were performed in 1 patient. RESULTS:
All patients showed bilateral and nearly symmetric cerebral white matter
hyperintensities on T2-weighted images, extending to the cerebellar white matter
and brain stem in 4. White matter, N-acetylaspartate, creatine, and choline
concentrations were significantly reduced compared with those in controls, with a
prominent increase in the radial water diffusivity component. At postmortem
examination, severe fibrosis of brain vessel smooth muscle was evident, along
with mitochondrial DNA replication depletion in brain and vascular smooth-muscle
and endothelial cells, without neuronal loss, myelin damage, or gliosis.
Prominent periependymal cytochrome C oxidase deficiency was also observed.
CONCLUSIONS: Vascular functional and histologic alterations account for
leukoencephalopathy in mitochondrial neurogastrointestinal encephalopathy.
Thymidine toxicity and mitochondrial DNA replication depletion may induce
microangiopathy and blood-brain-barrier dysfunction, leading to increased water
content in the white matter. Periependymal cytochrome C oxidase deficiency could
explain prominent periventricular impairment.
PMID- 29348135
TI - Development of High Signal Intensity within the Globus Pallidus and Dentate
Nucleus following Multiple Administrations of Gadobenate Dimeglumine.
AB - BACKGROUND AND PURPOSE: Previous studies have evaluated various gadolinium based
contrast agents and their association with gadolinium retention, however, there
is a discrepancy in the literature concerning the linear agent gadobenate
dimeglumine. Our aim was to determine whether an association exists between the
administration of gadobenate dimeglumine and the development of intrinsic T1
weighted signal in the dentate nucleus and globus pallidus. MATERIALS AND
METHODS: In this single-center, retrospective study, the signal intensity of the
globus pallidus, dentate nucleus, thalamus, and middle cerebellar peduncle was
measured on unenhanced T1-weighted images in 29 adult patients who had undergone
multiple contrast MRIs using exclusively gadobenate dimeglumine (mean, 10.1 +/-
3.23 doses; range, 6-18 doses). Two neuroradiologists, blinded to the number of
prior gadolinium-based contrast agent administrations, separately placed ROIs
within the globi pallidi, thalami, dentate nuclei, and middle cerebellar
peduncles on the last MR imaging examinations. The correlations between the
globus pallidus:thalamus and the dentate nucleus:middle cerebellar peduncle
signal intensity ratios with the number of gadolinium-based contrast agent
administrations and cumulative dose were tested with either 1-tailed Pearson or
Spearman correlations. A priori, P < .05 was considered statistically
significant. RESULTS: Both the globus pallidus:thalamus and dentate
nucleus:middle cerebellar peduncle ratios showed significant correlation with the
number of gadolinium-based contrast agent administrations (r = 0.39, P = .017,
and r = 0.58, P = .001, respectively). Additionally, the globus pallidus:thalamus
and dentate nucleus:middle cerebellar peduncle ratios showed significant
correlation with the cumulative dose of gadobenate dimeglumine (r = 0.48, P =
.004, and r = 0.43, P = .009, respectively). Dentate nucleus hyperintensity was
qualitatively present on the last MR imaging in 79.3%-86.2% of patients and in
all patients who had received >10 doses. CONCLUSIONS: At high cumulative doses
(commonly experienced by patients, for example, with neoplastic disease),
gadobenate dimeglumine is associated with an increase in the globus
pallidus:thalamus and dentate nucleus:middle cerebellar peduncles signal
intensity ratios.
PMID- 29348137
TI - Accuracy of the Compressed Sensing Accelerated 3D-FLAIR Sequence for the
Detection of MS Plaques at 3T.
AB - BACKGROUND AND PURPOSE: The use of 3D FLAIR improves the detection of brain
lesions in MS patients, but requires long acquisition times. Compressed sensing
reduces acquisition time by using the sparsity of MR images to randomly
undersample the k-space. Our aim was to compare the image quality and diagnostic
performance of 3D-FLAIR with and without compressed sensing for the detection of
multiple sclerosis lesions at 3T. MATERIALS AND METHODS: Twenty-three patients
with relapsing-remitting MS underwent both conventional 3D-FLAIR and compressed
sensing 3D-FLAIR on a 3T scanner (reduction in scan time 1 minute 25 seconds,
27%; compressed sensing factor of 1.3). Two blinded readers independently
evaluated both conventional and compressed sensing FLAIR for image quality (SNR
and contrast-to-noise ratio) and the number of MS lesions visible in the
periventricular, intra-juxtacortical, infratentorial, and optic nerve regions.
The volume of white matter lesions was measured with automatic postprocessing
segmentation software for each FLAIR sequence. RESULTS: Image quality and the
number of MS lesions detected by the readers were similar between the 2 FLAIR
acquisitions (P = .74 and P = .094, respectively). Almost perfect agreement was
found between both FLAIR acquisitions for total MS lesion count (Lin concordance
correlation coefficient = 0.99). Agreement between conventional and compressed
sensing FLAIR was almost perfect for periventricular and infratentorial lesions
and substantial for intrajuxtacortical and optic nerve lesions. Postprocessing
with the segmentation software did not reveal a significant difference between
conventional and compressed sensing FLAIR in total MS lesion volume (P = .63) or
the number of MS lesions (P = .15). CONCLUSIONS: With a compressed sensing factor
of 1.3, 3D-FLAIR is 27% faster and preserves diagnostic performance for the
detection of MS plaques at 3T.
PMID- 29348136
TI - Resting-State Functional MRI: Everything That Nonexperts Have Always Wanted to
Know.
AB - Resting-state fMRI was first described by Biswal et al in 1995 and has since then
been widely used in both healthy subjects and patients with various neurologic,
neurosurgical, and psychiatric disorders. As opposed to paradigm- or task-based
functional MR imaging, resting-state fMRI does not require subjects to perform
any specific task. The low-frequency oscillations of the resting-state fMRI
signal have been shown to relate to the spontaneous neural activity. There are
many ways to analyze resting-state fMRI data. In this review article, we will
briefly describe a few of these and highlight the advantages and limitations of
each. This description is to facilitate the adoption and use of resting-state
fMRI in the clinical setting, helping neuroradiologists become familiar with
these techniques and applying them for the care of patients with neurologic and
psychiatric diseases.
PMID- 29348138
TI - Development and validation of outcome prediction models for aneurysmal
subarachnoid haemorrhage: the SAHIT multinational cohort study.
AB - OBJECTIVE: To develop and validate a set of practical prediction tools that
reliably estimate the outcome of subarachnoid haemorrhage from ruptured
intracranial aneurysms (SAH). DESIGN: Cohort study with logistic regression
analysis to combine predictors and treatment modality. SETTING: Subarachnoid
Haemorrhage International Trialists' (SAHIT) data repository, including
randomised clinical trials, prospective observational studies, and hospital
registries. PARTICIPANTS: Researchers collaborated to pool datasets of
prospective observational studies, hospital registries, and randomised clinical
trials of SAH from multiple geographical regions to develop and validate clinical
prediction models. MAIN OUTCOME MEASURE: Predicted risk of mortality or
functional outcome at three months according to score on the Glasgow outcome
scale. RESULTS: Clinical prediction models were developed with individual patient
data from 10 936 patients and validated with data from 3355 patients after
development of the model. In the validation cohort, a core model including
patient age, premorbid hypertension, and neurological grade on admission to
predict risk of functional outcome had good discrimination, with an area under
the receiver operator characteristics curve (AUC) of 0.80 (95% confidence
interval 0.78 to 0.82). When the core model was extended to a "neuroimaging
model," with inclusion of clot volume, aneurysm size, and location, the AUC
improved to 0.81 (0.79 to 0.84). A full model that extended the neuroimaging
model by including treatment modality had AUC of 0.81 (0.79 to 0.83).
Discrimination was lower for a similar set of models to predict risk of mortality
(AUC for full model 0.76, 0.69 to 0.82). All models showed satisfactory
calibration in the validation cohort. CONCLUSION: The prediction models reliably
estimate the outcome of patients who were managed in various settings for
ruptured intracranial aneurysms that caused subarachnoid haemorrhage. The
predictor items are readily derived at hospital admission. The web based SAHIT
prognostic calculator (http://sahitscore.com) and the related app could be
adjunctive tools to support management of patients.
PMID- 29348139
TI - Dissecting the functions of SMG5, SMG7, and PNRC2 in nonsense-mediated mRNA decay
of human cells.
AB - The term "nonsense-mediated mRNA decay" (NMD) originally described the
degradation of mRNAs with premature translation-termination codons (PTCs), but
its meaning has recently been extended to be a translation-dependent post
transcriptional regulator of gene expression affecting 3%-10% of all mRNAs. The
degradation of NMD target mRNAs involves both exonucleolytic and endonucleolytic
pathways in mammalian cells. While the latter is mediated by the endonuclease
SMG6, the former pathway has been reported to require a complex of SMG5-SMG7 or
SMG5-PNRC2 binding to UPF1. However, the existence, dominance, and mechanistic
details of these exonucleolytic pathways are divisive. Therefore, we have
investigated the possible exonucleolytic modes of mRNA decay in NMD by examining
the roles of UPF1, SMG5, SMG7, and PNRC2 using a combination of functional assays
and interaction mapping. Confirming previous work, we detected an interaction
between SMG5 and SMG7 and also a functional need for this complex in NMD. In
contrast, we found no evidence for the existence of a physical or functional
interaction between SMG5 and PNRC2. Instead, we show that UPF1 interacts with
PNRC2 and that it triggers 5'-3' exonucleolytic decay of reporter transcripts in
tethering assays. PNRC2 interacts mainly with decapping factors and its knockdown
does not affect the RNA levels of NMD reporters. We conclude that PNRC2 is
probably an important mRNA decapping factor but that it does not appear to be
required for NMD.
PMID- 29348140
TI - Interactions, localization, and phosphorylation of the m6A generating METTL3
METTL14-WTAP complex.
AB - N6-methyladenine (m6A) is found on many eukaryotic RNAs including mRNAs. m6A
modification has been implicated in mRNA stability and turnover, localization, or
translation efficiency. A heterodimeric enzyme complex composed of METTL3 and
METTL14 generates m6A on mRNAs. METTL3/14 is found in the nucleus where it is
localized to nuclear speckles and the splicing regulator WTAP is required for
this distinct nuclear localization pattern. Although recent crystal structures
revealed how the catalytic MT-A70 domains of METTL3 and METTL14 interact with
each other, a more global architecture including WTAP and RNA interactions has
not been reported so far. Here, we used recombinant proteins and mapped binding
surfaces within the METTL3/14-WTAP complex. Furthermore, we identify nuclear
localization signals and identify phosphorylation sites on the endogenous
proteins. Using an in vitro methylation assay, we confirm that monomeric METTL3
is soluble and inactive while the catalytic center of METTL14 is degenerated and
thus also inactive. In addition, we show that the C-terminal RGG repeats of
METTL14 are required for METTL3/14 activity by contributing to RNA substrate
binding. Our biochemical work identifies characteristic features of METTL3/14
WTAP and reveals novel insight into the overall architecture of this important
enzyme complex.
PMID- 29348141
TI - CELLULASE6 and MANNANASE7 Affect Cell Differentiation and Silique Dehiscence.
AB - Cellulases, hemicellulases, and pectinases play important roles in fruit
development and maturation. Although mutants with defects in these processes have
not been reported for cellulase or hemicellulase genes, the pectinases
ARABIDOPSIS DEHISCENCE ZONE POLYGALACTURONASE1 (ADPG1) and ADPG2 were previously
shown to be essential for silique dehiscence in Arabidopsis (Arabidopsis
thaliana). Here, we demonstrate that the cellulase gene CELLULASE6 (CEL6) and the
hemicellulase gene MANNANASE7 (MAN7) function in the development and dehiscence
of Arabidopsis siliques. We found that these genes were expressed in both
vegetative and reproductive organs and that their expression in the silique
partially depended on the INDEHISCENT and ALCATRAZ transcription factors. Cell
differentiation was delayed in the dehiscence zone of cel6 and man7 mutant
siliques at early flower development stage 17, and a comparison of the spatio
temporal patterns of CEL6 and MAN7 expression with the locations of delayed cell
differentiation in the cel6 and man7 mutants revealed that CEL6 and MAN7 likely
indirectly affect the timing of cell differentiation in the silique valve at this
stage. CEL6 and MAN7 were also found to promote cell degeneration in the
separation layer in nearly mature siliques, as cells in this layer remained
intact in the cel6 and man7 mutants and the cel6-1 man7-3 double mutant, whereas
they degenerated in the wild-type control. Phenotypic studies of single, double,
triple, and quadruple mutants revealed that higher-order mutant combinations of
cel6-1, man7-3, and adpg1-1 and adpg2-1 produced more severe silique indehiscent
phenotypes than the corresponding lower-order mutant combinations, except for
some combinations involving cel6-1, man7-3, and adpg2-1 Our results demonstrate
that the ability of the silique to dehisce can be manipulated to different
degrees by altering the activities of various cell wall-modifying enzymes.
PMID- 29348142
TI - SEMA3C drives cancer growth by transactivating multiple receptor tyrosine kinases
via Plexin B1.
AB - Growth factor receptor tyrosine kinase (RTK) pathway activation is a key
mechanism for mediating cancer growth, survival, and treatment resistance.
Cognate ligands play crucial roles in autocrine or paracrine stimulation of these
RTK pathways. Here, we show SEMA3C drives activation of multiple RTKs including
EGFR, ErbB2, and MET in a cognate ligand-independent manner via Plexin B1. SEMA3C
expression levels increase in castration-resistant prostate cancer (CRPC), where
it functions to promote cancer cell growth and resistance to androgen receptor
pathway inhibition. SEMA3C inhibition delays CRPC and enzalutamide-resistant
progression. Plexin B1 sema domain-containing:Fc fusion proteins suppress RTK
signaling and cell growth and inhibit CRPC progression of LNCaP xenografts post
castration in vivo SEMA3C inhibition represents a novel therapeutic strategy for
treatment of advanced prostate cancer.
PMID- 29348143
TI - Detecting Polygenic Adaptation in Admixture Graphs.
AB - An open question in human evolution is the importance of polygenic adaptation:
adaptive changes in the mean of a multifactorial trait due to shifts in allele
frequencies across many loci. In recent years, several methods have been
developed to detect polygenic adaptation using loci identified in genome-wide
association studies (GWAS). Though powerful, these methods suffer from limited
interpretability: they can detect which sets of populations have evidence for
polygenic adaptation, but are unable to reveal where in the history of multiple
populations these processes occurred. To address this, we created a method to
detect polygenic adaptation in an admixture graph, which is a representation of
the historical divergences and admixture events relating different populations
through time. We developed a Markov chain Monte Carlo (MCMC) algorithm to infer
branch-specific parameters reflecting the strength of selection in each branch of
a graph. Additionally, we developed a set of summary statistics that are fast to
compute and can indicate which branches are most likely to have experienced
polygenic adaptation. We show via simulations that this method-which we call
PolyGraph-has good power to detect polygenic adaptation, and applied it to human
population genomic data from around the world. We also provide evidence that
variants associated with several traits, including height, educational
attainment, and self-reported unibrow, have been influenced by polygenic
adaptation in different populations during human evolution.
PMID- 29348145
TI - FBXL13 directs the proteolysis of CEP192 to regulate centrosome homeostasis and
cell migration.
AB - Aberrant centrosome organisation with ensuing alterations of microtubule
nucleation capacity enables tumour cells to proliferate and invade despite
increased genomic instability. CEP192 is a key factor in the initiation process
of centrosome duplication and in the control of centrosome microtubule
nucleation. However, regulatory means of CEP192 have remained unknown. Here, we
report that FBXL13, a binding determinant of SCF (SKP1-CUL1-F-box)-family E3
ubiquitin ligases, is enriched at centrosomes and interacts with the centrosomal
proteins Centrin-2, Centrin-3, CEP152 and CEP192. Among these, CEP192 is
specifically targeted for proteasomal degradation by FBXL13. Accordingly, induced
FBXL13 expression downregulates centrosomal gamma-tubulin and disrupts
centrosomal microtubule arrays. In addition, depletion of FBXL13 induces high
levels of CEP192 and gamma-tubulin at the centrosomes with the consequence of
defects in cell motility. Together, we characterise FBXL13 as a novel regulator
of microtubule nucleation activity and highlight a role in promoting cell
motility with potential tumour-promoting implications.
PMID- 29348146
TI - The INs and OUTs of mitofusins.
AB - Mitofusins are outer membrane proteins essential for mitochondrial fusion. Their
accepted topology posits that both N and C termini face the cytoplasm. In this
issue, Mattie et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201611194)
demonstrate instead that their C termini reside in the intermembrane space. These
findings call for a revision of the current models of mitochondrial fusion.
PMID- 29348144
TI - A CRISPR Tagging-Based Screen Reveals Localized Players in Wnt-Directed
Asymmetric Cell Division.
AB - Oriented cell divisions are critical to establish and maintain cell fates and
tissue organization. Diverse extracellular and intracellular cues have been shown
to provide spatial information for mitotic spindle positioning; however, the
molecular mechanisms by which extracellular signals communicate with cells to
direct mitotic spindle positioning are largely unknown. In animal cells, oriented
cell divisions are often achieved by the localization of force-generating motor
protein complexes to discrete cortical domains. Disrupting either these force
generating complexes or proteins that globally affect microtubule stability
results in defects in mitotic positioning, irrespective of whether these proteins
function as spatial cues for spindle orientation. This poses a challenge to
traditional genetic dissection of this process. Therefore, as an alternative
strategy to identify key proteins that act downstream of intercellular signaling,
we screened the localization of many candidate proteins by inserting fluorescent
tags directly into endogenous gene loci, without overexpressing the proteins. We
tagged 23 candidate proteins in Caenorhabditis elegans and examined each
protein's localization in a well-characterized, oriented cell division in the
four-cell-stage embryo. We used cell manipulations and genetic experiments to
determine which cells harbor key localized proteins and which signals direct
these localizations in vivo We found that Dishevelled and adenomatous polyposis
coli homologs are polarized during this oriented cell division in response to a
Wnt signal, but two proteins typically associated with mitotic spindle
positioning, homologs of NuMA and Dynein, were not detectably polarized. These
results suggest an unexpected mechanism for mitotic spindle positioning in this
system, they pinpoint key proteins of interest, and they highlight the utility of
a screening approach based on analyzing the localization of endogenously tagged
proteins.
PMID- 29348147
TI - Bao-Liang Song: Loving biology in the time of cholesterol.
AB - Song studies the trafficking and biological activities of cholesterol.
PMID- 29348148
TI - Replication timing kept in LINE.
AB - Accurate and synchronous replication timing between chromosome homologues is
essential for maintaining chromosome stability, yet how this is achieved has
remained a mystery. In this issue, Platt et al. (2018. J. Cell Biol.
https://doi.org/10.1083/jcb.201707082) identify antisense LINE (L1) transcripts
within long noncoding RNAs as the critical factor in maintaining synchronous
chromosome-wide replication timing.
PMID- 29348150
TI - GMC erasure case: how we learn from human error.
PMID- 29348151
TI - AHRR hypomethylation, lung function, lung function decline and respiratory
symptoms.
AB - Epigenome-wide association studies have shown a consistent association between
smoking exposure and hypomethylation in the aryl hydrocarbon receptor repressor
(AHRR) gene (cg05575921). We tested the hypothesis that AHRR hypomethylation is
associated with low lung function, steeper lung function decline, and respiratory
symptoms in the general population.AHRR methylation extent was measured in 9113
individuals from the 1991-1994 examination of the Copenhagen City Heart Study,
using bisulfite-treated leukocyte DNA. Spirometry at the time of blood sampling
was available for all individuals. Lung function was measured again for 4532 of
these individuals in 2001-2003.Cross-sectionally, a 10% lower methylation extent
was associated with a 0.2 z-score (95% CI 0.1-0.2) lower forced expiratory volume
in 1 s (FEV1) after multivariable adjustment including smoking. Hypomethylation
was also associated with a lower z-score for both forced vital capacity (FVC) and
FEV1/FVC. In prospective analyses, individuals in the lowest versus highest
tertile of methylation extent had a steeper decline in FEV1/height3 (p for
examination*methylation interaction=0.003) and FVC/height3 (p=0.01), but not
FEV1/FVC (p=0.08). Multivariable-adjusted odds ratios per 10% lower methylation
extent were 1.31 (95% CI 1.18-1.45) for chronic bronchitis and 1.21 (95% CI 1.13
1.30) for any respiratory symptoms.AHRR hypomethylation was associated with low
lung function, steeper lung function decline, and respiratory symptoms.
PMID- 29348152
TI - Hearing loss with kanamycin treatment for multidrug-resistant tuberculosis in
Bangladesh.
PMID- 29348153
TI - First histopathological evidence of irreversible pulmonary vascular disease in
dasatinib-induced pulmonary arterial hypertension.
PMID- 29348154
TI - Differential diagnosis between newly diagnosed asthma and COPD using exhaled
breath condensate metabolomics: a pilot study.
PMID- 29348155
TI - Mesenchymal stromal cell infusion modulates systemic immunological responses in
stable COPD patients: a phase I pilot study.
PMID- 29348156
TI - Development and feasibility of an eHealth tool for idiopathic pulmonary fibrosis.
PMID- 29348159
TI - Correction: Introduction of allergenic foods from 3 months of age reduces
incidence of food allergy in breastfed infants.
PMID- 29348157
TI - GMC erasure case: we must improve systems to mitigate inevitable mistakes.
PMID- 29348160
TI - Up all night: BK channels' circadian dance with different calcium sources.
AB - JGP study explores diurnal changes in calcium sources governing BK activity in
the SCN.
PMID- 29348161
TI - CNS Metastases Needn't Rule Out Trial Inclusion.
AB - New guidelines from an expert working group describe when to include or exclude
patients with brain metastases from clinical trials. In the past, these patients
have often been inappropriately excluded from trials, resulting in a dearth of
information on the efficacy of cancer drugs in the central nervous system.
PMID- 29348162
TI - Mutation Burden Predicts Anti-PD-1 Response.
AB - A new study finds that objective response rates to anti-PD-1 therapies correlate
with tumor mutation burden for most of the 27 cancer types studied. Objective
response rates were higher than expected for Merkel cell carcinoma and renal cell
carcinoma, which may be particularly immunogenic. The objective response rate was
unexpectedly low for colorectal cancer with mismatch repair proficiency.
PMID- 29348163
TI - IFCC Working Group Recommendations for Assessing Commutability Part 1: General
Experimental Design.
AB - Commutability is a property of a reference material (RM) that relates to the
closeness of agreement between results for an RM and results for clinical samples
(CSs) when measured by >=2 measurement procedures (MPs). Commutability of RMs
used in a calibration traceability scheme is an essential property for them to be
fit for purpose. Similarly, commutability of trueness controls or external
quality assessment samples is essential when those materials are used to assess
trueness of results for CSs. This report is part 1 of a 3-part series describing
how to assess commutability of RMs. Part 1 defines commutability and addresses
critical components of the experimental design for commutability assessment,
including selection of individual CSs, use of pooled CSs, qualification of MPs
for inclusion, establishing criteria for the determination that an RM is
commutable, generalization of commutability conclusions to future measurements
made with the MPs included in the assessment, and information regarding
commutability to be included in the certificate for an RM. Parts 2 and 3 in the
series present 2 different statistical approaches to commutability assessment
that use fixed criteria related to the medical decisions that will be made using
the laboratory test results.
PMID- 29348164
TI - IFCC Working Group Recommendations for Assessing Commutability Part 3: Using the
Calibration Effectiveness of a Reference Material.
AB - A process is described to assess the commutability of a reference material (RM)
intended for use as a calibrator based on its ability to fulfill its intended use
in a calibration traceability scheme to produce equivalent clinical sample (CS)
results among different measurement procedures (MPs) for the same measurand.
Three sources of systematic error are elucidated in the context of creating the
calibration model for translating MP signals to measurand amounts: calibration
fit, calibrator level trueness, and commutability. An example set of 40 CS
results from 7 MPs is used to illustrate estimation of bias and variability for
each MP. The candidate RM is then used to recalibrate each MP, and its
effectiveness in reducing the systematic error among the MPs within an acceptable
level of equivalence based on medical requirements confirms its commutability for
those MPs. The RM is declared noncommutable for MPs for which, after
recalibration, the CS results do not agree with those from other MPs. When a lack
of agreement is found, other potential causes, including lack of calibration fit,
should be investigated before concluding the RM is noncommutable. The RM is
considered fit for purpose for those MPs where commutability is demonstrated.
PMID- 29348165
TI - IFCC Working Group Recommendations for Assessing Commutability Part 2: Using the
Difference in Bias between a Reference Material and Clinical Samples.
AB - A process is described to assess the commutability of a reference material (RM)
intended for use as a calibrator, trueness control, or external quality
assessment sample based on the difference in bias between an RM and clinical
samples (CSs) measured using 2 different measurement procedures (MPs). This
difference in bias is compared with a criterion based on a medically relevant
difference between an RM and CS results to make a conclusion regarding
commutability. When more than 2 MPs are included, the commutability is assessed
pairwise for all combinations of 2 MPs. This approach allows the same criterion
to be used for all combinations of MPs included in the assessment. The assessment
is based on an error model that allows estimation of various random and
systematic sources of error, including those from sample-specific effects of
interfering substances. An advantage of this approach is that the difference in
bias between an RM and the average bias of CSs at the concentration (i.e., amount
of substance present or quantity value) of the RM is determined and its
uncertainty estimated. An RM is considered fit for purpose for those MPs for
which commutability is demonstrated.
PMID- 29348166
TI - Clinical Evaluation of a Blood Assay to Diagnose Paucibacillary Tuberculosis via
Bacterial Antigens.
AB - BACKGROUND: The diagnosis of active tuberculosis (TB) cases primarily relies on
methods that detect Mycobacterium tuberculosis (Mtb) bacilli or their DNA in
patient samples (e.g., mycobacterial culture and Xpert MTB/RIF assays), but these
tests have low clinical sensitivity for patients with paucibacillary TB disease.
Our goal was to evaluate the clinical performance of a newly developed assay that
can rapidly diagnose active TB cases by direct detection of Mtb-derived antigens
in patients' blood samples. METHODS: Nanoparticle (NanoDisk)-enriched peptides
derived from the Mtb virulence factors CFP-10 (10-kDa culture factor protein) and
ESAT-6 (6-kDa early secretory antigenic target) were analyzed by high-throughput
mass spectrometry (MS). Serum from 294 prospectively enrolled Chinese adults were
analyzed with this NanoDisk-MS method to evaluate the performance of direct serum
Mtb antigen measurement as a means for rapid diagnosis of active TB cases.
RESULTS: NanoDisk-MS diagnosed 174 (88.3%) of the study's TB cases, with 95.8%
clinical specificity, and with 91.6% and 85.3% clinical sensitivity for culture
positive and culture-negative TB cases, respectively. NanoDisk-MS also exhibited
88% clinical sensitivity for pulmonary and 90% for extrapulmonary TB, exceeding
the diagnostic performance of mycobacterial culture for these cases. CONCLUSIONS:
Direct detection and quantification of serum Mtb antigens by NanoDisk-MS can
rapidly and accurately diagnose active TB in adults, independent of disease site
or culture status, and outperform Mycobacterium-based TB diagnostics.
PMID- 29348167
TI - Thiosulfate sulfurtransferase-like domain-containing 1 protein interacts with
thioredoxin.
AB - Rhodanese domains are structural modules present in the sulfurtransferase
superfamily. These domains can exist as single units, in tandem repeats, or fused
to domains with other activities. Despite their prevalence across species, the
specific physiological roles of most sulfurtransferases are not known. Mammalian
rhodanese and mercaptopyruvate sulfurtransferase are perhaps the best-studied
members of this protein superfamily and are involved in hydrogen sulfide
metabolism. The relatively unstudied human thiosulfate sulfurtransferase-like
domain-containing 1 (TSTD1) protein, a single-domain cytoplasmic
sulfurtransferase, was also postulated to play a role in the sulfide oxidation
pathway using thiosulfate to form glutathione persulfide, for subsequent
processing in the mitochondrial matrix. Prior kinetic analysis of TSTD1 was
performed at pH 9.2, raising questions about relevance and the proposed model for
TSTD1 function. In this study, we report a 1.04 A resolution crystal structure of
human TSTD1, which displays an exposed active site that is distinct from that of
rhodanese and mercaptopyruvate sulfurtransferase. Kinetic studies with a
combination of sulfur donors and acceptors reveal that TSTD1 exhibits a low Km
for thioredoxin as a sulfane sulfur acceptor and that it utilizes thiosulfate
inefficiently as a sulfur donor. The active site exposure and its interaction
with thioredoxin suggest that TSTD1 might play a role in sulfide-based signaling.
The apical localization of TSTD1 in human colonic crypts, which interfaces with
sulfide-releasing microbes, and the overexpression of TSTD1 in colon cancer
provide potentially intriguing clues as to its role in sulfide metabolism.
PMID- 29348168
TI - The phospholipid-repair system LplT/Aas in Gram-negative bacteria protects the
bacterial membrane envelope from host phospholipase A2 attack.
AB - Secretory phospholipases A2 (sPLA2s) are potent components of mammalian innate
immunity antibacterial mechanisms. sPLA2 enzymes attack bacteria by hydrolyzing
bacterial membrane phospholipids, causing membrane disorganization and cell
lysis. However, most Gram-negative bacteria are naturally resistant to sPLA2 Here
we report a novel resistance mechanism to mammalian sPLA2 in Escherichia coli,
mediated by a phospholipid repair system consisting of the lysophospholipid
transporter LplT and the acyltransferase Aas in the cytoplasmic membrane.
Mutation of the lplT or aas gene abolished bacterial lysophospholipid acylation
activity and drastically increased bacterial susceptibility to the combined
actions of inflammatory fluid components and sPLA2, resulting in bulk
phospholipid degradation and loss of colony-forming ability. sPLA2-mediated
hydrolysis of the three major bacterial phospholipids exhibited distinctive
kinetics and deacylation of cardiolipin to its monoacyl-derivative closely
paralleled bacterial death. Characterization of the membrane envelope in lplT- or
aas-knockout mutant bacteria revealed reduced membrane packing and disruption of
lipid asymmetry with more phosphatidylethanolamine present in the outer leaflet
of the outer membrane. Moreover, modest accumulation of lysophospholipids in
these mutant bacteria destabilized the inner membrane and rendered outer membrane
depleted spheroplasts much more sensitive to sPLA2 These findings indicated that
LplT/Aas inactivation perturbs both the outer and inner membranes by bypassing
bacterial membrane maintenance mechanisms to trigger specific interfacial
activation of sPLA2 We conclude that the LplT/Aas system is important for
maintaining the integrity of the membrane envelope in Gram-negative bacteria. Our
insights may help inform new therapeutic strategies to enhance host sPLA2
antimicrobial activity.
PMID- 29348169
TI - Lipid-mediated signals that regulate mitochondrial biology.
AB - For decades, lipids were assumed to fulfill roles only in energy storage and
membrane structure. Recent studies have discovered critical roles for
phospholipids, sphingolipids, and sterols in many cellular pathways, including
cell signaling and transcriptional regulation. Frequently, lipids from these
various classes work together to achieve defined cellular outcomes. Specific
mitochondrial lipids are critical for proper assembly of the electron transport
chain complexes and for effective responses to mitochondrial damage, including
maintenance of mitochondrial protein homeostasis, regulation of mitophagy, and
induction of apoptosis. In this Minireview, we will primarily focus on
mitochondrial lipid signaling mediated by lipid-protein interactions.
PMID- 29348170
TI - CRISPR RNA and anti-CRISPR protein binding to the Xanthomonas albilineans Csy1
Csy2 heterodimer in the type I-F CRISPR-Cas system.
AB - Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR
associated (Cas) proteins provide microbial adaptive immunity against
bacteriophages. In type I-F CRISPR-Cas systems, multiple Cas proteins (Csy1-4)
compose a surveillance complex (Csy complex) with CRISPR RNA (crRNA) for target
recognition. Here, we report the biochemical characterization of the Csy1-Csy2
subcomplex from Xanthomonas albilineans, including the analysis of its
interaction with crRNA and AcrF2, an anti-CRISPR (Acr) protein from a phage that
infects Pseudomonas aeruginosa The X. albilineans Csy1 and Csy2 proteins (XaCsy1
and XaCsy2, respectively) formed a stable heterodimeric complex that specifically
bound the 8-nucleotide (nt) 5'-handle of the crRNA. In contrast, the XaCsy1
XaCsy2 heterodimer exhibited reduced affinity for the 28-nt X. albilineans CRISPR
repeat RNA containing the 5'-handle sequence. Chromatographic and calorimetric
analyses revealed tight binding between the Acr protein from the P. aeruginosa
phage and the heterodimeric subunit of the X. albilineans Csy complex, suggesting
that AcrF2 recognizes conserved features of Csy1-Csy2 heterodimers. We found that
neither XaCsy1 nor XaCsy2 alone forms a stable complex with AcrF2 and the 5'
handle RNA, indicating that XaCsy1-XaCsy2 heterodimerization is required for
binding them. We also solved the crystal structure of AcrF2 to a resolution of
1.34 A, enabling a more detailed structural analysis of the residues involved in
the interactions with the Csy1-Csy2 heterodimer. Our results provide information
about the order of events during the formation of the multisubunit crRNA-guided
surveillance complex and suggest that the Acr protein inactivating type I-F
CRISPR-Cas systems has broad specificity.
PMID- 29348171
TI - A cationic, C-terminal patch and structural rearrangements in Ebola virus matrix
VP40 protein control its interactions with phosphatidylserine.
AB - Ebola virus (EBOV) is a filamentous lipid-enveloped virus that causes hemorrhagic
fever with a high fatality rate. Viral protein 40 (VP40) is the major EBOV matrix
protein and regulates viral budding from the plasma membrane. VP40 is a
transformer/morpheein that can structurally rearrange its native homodimer into
either a hexameric filament that facilitates viral budding or an RNA-binding
octameric ring that regulates viral transcription. VP40 associates with plasma
membrane lipids such as phosphatidylserine (PS), and this association is critical
to budding from the host cell. However, it is poorly understood how different
VP40 structures interact with PS, what essential residues are involved in this
association, and whether VP40 has true selectivity for PS among different
glycerophospholipid headgroups. In this study, we used lipid-binding assays, MD
simulations, and cellular imaging to investigate the molecular basis of VP40-PS
interactions and to determine whether different VP40 structures (i.e. monomer,
dimer, and octamer) can interact with PS-containing membranes. Results from
quantitative analysis indicated that VP40 associates with PS vesicles via a
cationic patch in the C-terminal domain (Lys224, 225 and Lys274, 275).
Substitutions of these residues with alanine reduced PS-vesicle binding by >40
fold and abrogated VP40 localization to the plasma membrane. Dimeric VP40 had 2
fold greater affinity for PS-containing membranes than the monomer, whereas
binding of the VP40 octameric ring was reduced by nearly 10-fold. Taken together,
these results suggest the different VP40 structures known to form in the viral
life cycle harbor different affinities for PS-containing membranes.
PMID- 29348172
TI - The alpha-arrestin ARRDC3 suppresses breast carcinoma invasion by regulating G
protein-coupled receptor lysosomal sorting and signaling.
AB - Aberrant G protein-coupled receptor (GPCR) expression and activation has been
linked to tumor initiation, progression, invasion, and metastasis. However,
compared with other cancer drivers, the exploitation of GPCRs as potential
therapeutic targets has been largely ignored, despite the fact that GPCRs are
highly druggable. Therefore, to advance the potential status of GPCRs as
therapeutic targets, it is important to understand how GPCRs function together
with other cancer drivers during tumor progression. We now report that the alpha
arrestin domain-containing protein-3 (ARRDC3) acts as a tumor suppressor in part
by controlling signaling and trafficking of the GPCR, protease-activated receptor
1 (PAR1). In a series of highly invasive basal-like breast carcinomas, we found
that expression of ARRDC3 is suppressed whereas PAR1 is aberrantly overexpressed
because of defective lysosomal sorting that results in persistent signaling.
Using a lentiviral doxycycline-inducible system, we demonstrate that re
expression of ARRDC3 in invasive breast carcinoma is sufficient to restore normal
PAR1 trafficking through the ALG-interacting protein X (ALIX)-dependent lysosomal
degradative pathway. We also show that ARRDC3 re-expression attenuates PAR1
stimulated persistent signaling of c-Jun N-terminal kinase (JNK) in invasive
breast cancer. Remarkably, restoration of ARRDC3 expression significantly reduced
activated PAR1-induced breast carcinoma invasion, which was also dependent on JNK
signaling. These findings are the first to identify a critical link between the
tumor suppressor ARRDC3 and regulation of GPCR trafficking and signaling in
breast cancer.
PMID- 29348173
TI - Methanobactins: Maintaining copper homeostasis in methanotrophs and beyond.
AB - Methanobactins (Mbns) are ribosomally produced, post-translationally modified
natural products that bind copper with high affinity and specificity. Originally
identified in methanotrophic bacteria, which have a high need for copper, operons
encoding these compounds have also been found in many non-methanotrophic
bacteria. The proteins responsible for Mbn biosynthesis include several novel
enzymes. Mbn transport involves export through a multidrug efflux pump and re
internalization via a TonB-dependent transporter. Release of copper from Mbn and
the molecular basis for copper regulation of Mbn production remain to be
elucidated. Future work is likely to result in the identification of new
enzymatic chemistry, opportunities for bioengineering and drug targeting of
copper metabolism, and an expanded understanding of microbial metal homeostasis.
PMID- 29348175
TI - Glucose regulates MafA transcription factor abundance and insulin gene expression
by inhibiting AMP-activated protein kinase in pancreatic beta-cells.
AB - Insulin mRNA expression in pancreatic islet beta-cells is up-regulated by
extracellular glucose concentration, but the underlying mechanism remains
incompletely understood. MafA is a transcriptional activator specifically
enriched in beta-cells that binds to the insulin gene promoter. Its expression is
transcriptionally and posttranscriptionally regulated by glucose. Moreover, AMP
activated protein kinase (AMPK), a regulator of cellular energy homeostasis, is
inhibited by high glucose, and this inhibition is essential for the up-regulation
of insulin gene expression and glucose-stimulated insulin secretion (GSIS). Here
we mutagenized the insulin promoter and found that the MafA-binding element
C1/RIPE3b is required for glucose- or AMPK-induced alterations in insulin gene
promoter activity. Under high-glucose conditions, pharmacological activation of
AMPK in isolated mouse islets or MIN6 cells by metformin or 5-aminoimidazole-4
carboxamide riboside decreased MafA protein levels and mRNA expression of insulin
and GSIS-related genes (i.e. glut2 and sur1). Overexpression of constitutively
active AMPK also reduced MafA and insulin expression. Conversely, pharmacological
AMPK inhibition by dorsomorphin (compound C) or expression of a dominant-negative
form of AMPK increased MafA and insulin expression under low-glucose conditions.
However, AMPK activation or inhibition did not change the expression levels of
the beta-cell-enriched transcription factors Pdx1 and Beta2/NeuroD1. AMPK
activation accelerated MafA protein degradation, which is not dependent on the
proteasome. We also noted that MafA overexpression prevents metformin-induced
decreases in insulin and GSIS-related gene expression. These findings indicate
that high glucose concentrations inhibit AMPK, thereby increasing MafA protein
levels and activating the insulin promoter.
PMID- 29348174
TI - Oligomer formation and G-quadruplex binding by purified murine Rif1 protein, a
key organizer of higher-order chromatin architecture.
AB - Rap1-interacting protein 1 (Rif1) regulates telomere length in budding yeast. We
previously reported that, in metazoans and fission yeast, Rif1 also plays pivotal
roles in controlling genome-wide DNA replication timing. We proposed that Rif1
may assemble chromatin compartments that contain specific replication-timing
domains by promoting chromatin loop formation. Rif1 also is involved in DNA
lesion repair, restart after replication fork collapse, anti-apoptosis
activities, replicative senescence, and transcriptional regulation. Although
multiple physiological functions of Rif1 have been characterized, biochemical and
structural information on mammalian Rif1 is limited, mainly because of
difficulties in purifying the full-length protein. Here, we expressed and
purified the 2418-amino-acid-long, full-length murine Rif1 as well as its
partially truncated variants in human 293T cells. Hydrodynamic analyses indicated
that Rif1 forms elongated or extended homo-oligomers in solution, consistent with
the presence of a HEAT-type helical repeat segment known to adopt an elongated
shape. We also observed that the purified murine Rif1 bound G-quadruplex (G4) DNA
with high specificity and affinity, as was previously shown for Rif1 from fission
yeast. Both the N-terminal (HEAT-repeat) and C-terminal segments were involved in
oligomer formation and specifically bound G4 DNA, and the central intrinsically
disordered polypeptide segment increased the affinity for G4. Of note, pulldown
assays revealed that Rif1 simultaneously binds multiple G4 molecules. Our
findings support a model in which Rif1 modulates chromatin loop structures
through binding to multiple G4 assemblies and by holding chromatin fibers
together.
PMID- 29348177
TI - Dasatinib increases endothelial permeability leading to pleural effusion.
AB - Pleural effusion is a frequent side-effect of dasatinib, a second-generation
tyrosine kinase inhibitor used in the treatment of chronic myelogenous leukaemia.
However, the underlying mechanisms remain unknown. We hypothesised that dasatinib
alters endothelial integrity, resulting in increased pulmonary vascular
endothelial permeability and pleural effusion.To test this, we established the
first animal model of dasatinib-related pleural effusion, by treating rats with a
daily regimen of high doses of dasatinib (10 mg.kg-1.day-1 for 8 weeks).Pleural
ultrasonography revealed that rats chronically treated with dasatinib developed
pleural effusion after 5 weeks. Consistent with these in vivo observations,
dasatinib led to a rapid and reversible increase in paracellular permeability of
human pulmonary endothelial cell monolayers as reflected by increased
macromolecule passage, loss of vascular endothelial cadherin and zonula occludens
1 from cell-cell junctions, and the development of actin stress fibres. These
results were replicated using human umbilical vein endothelial cells and
confirmed by decreased endothelial resistance. Interestingly, we demonstrated
that this increased endothelial permeability is a reactive oxygen species (ROS)
dependent mechanism in vitro and in vivo using a cotreatment with an antioxidant
agent, N-acetylcysteine.This study shows that dasatinib alters pulmonary
endothelial permeability in a ROS-dependent manner in vitro and in vivo leading
to pleural effusion.
PMID- 29348176
TI - Contribution of the tRNAIle 4317A->G mutation to the phenotypic manifestation of
the deafness-associated mitochondrial 12S rRNA 1555A->G mutation.
AB - The 1555A->G mutation in mitochondrial 12S rRNA has been associated with
aminoglycoside-induced and non-syndromic deafness in many individuals worldwide.
Mitochondrial genetic modifiers are proposed to influence the phenotypic
expression of m.1555A->G mutation. Here, we report that a deafness-susceptibility
allele (m.4317A->G) in the tRNAIle gene modulates the phenotype expression of
m.1555A->G mutation. Strikingly, a large Han Chinese pedigree carrying both
m.4317A->G and m.1555A->G mutations exhibited much higher penetrance of deafness
than those carrying only the m.1555A->G mutation. The m.4317A->G mutation
affected a highly conserved adenine at position 59 in the T-loop of tRNAIle We
therefore hypothesized that the m.4317A->G mutation alters both structure and
function of tRNAIle Using lymphoblastoid cell lines derived from members of
Chinese families (three carrying both m.1555A->G and m.4317A->G mutations, three
harboring only m.1555A->G mutation, and three controls lacking these mutations),
we found that the cell lines bearing both m.4317A->G and m.1555A->G mutations
exhibited more severe mitochondrial dysfunctions than those carrying only the
m.1555A->G mutation. We also found that the m.4317A->G mutation perturbed the
conformation, stability, and aminoacylation efficiency of tRNAIle These m.4317A
>G mutation-induced alterations in tRNAIle structure and function aggravated the
defective mitochondrial translation and respiratory phenotypes associated with
the m.1555A->G mutation. Furthermore, mutant cell lines bearing both m.4317A->G
and m.1555A->G mutations exhibited greater reductions in the mitochondrial ATP
levels and membrane potentials and increasing production of reactive oxygen
species than those carrying only the m.1555A->G mutation. Our findings provide
new insights into the pathophysiology of maternally inherited deafness arising
from the synergy between mitochondrial 12S rRNA and tRNA mutations.
PMID- 29348178
TI - A scoring system to predict the elevation of mean pulmonary arterial pressure in
idiopathic pulmonary fibrosis.
AB - Elevated mean pulmonary arterial pressure (MPAP; >=21 mmHg) is sometimes seen in
patients with idiopathic pulmonary fibrosis (IPF) and has an adverse impact upon
survival. Although early diagnosis is crucial, there is no established screening
tool that uses a combination of noninvasive examinations.We retrospectively
analysed IPF patients at initial evaluation from April 2007 to July 2015 and,
using logistic regression analysis, created a screening tool to identify elevated
MPAP. Internal validation was also assessed for external validity using a
bootstrap method.Using right-heart catheterisation (RHC), elevation of MPAP was
determined to be present in 55 out of 273 patients. Multivariate models
demonstrated that % predicted diffusing capacity of the lung for carbon monoxide
(DLCO) <50%, ratio of pulmonary artery diameter to aorta diameter (PA/Ao) on
computed tomography (CT) >=0.9 and arterial oxygen tension (PaO2 ) <80 Torr were
independent predictors. When we assigned a single point to each variable, the
prevalence of elevation of MPAP with a score of zero, one, two or three points
was 6.7%, 16.0%, 29.1% and 65.4%, respectively. The area under curve (AUC) for
the receiver operating characteristic (ROC) curve was good at 0.757 (95% CI 0.682
0.833).A simple clinical scoring system consisting of % predicted DLCO, PA/Ao
ratio on CT and PaO2 can easily predict elevation of MPAP in patients with IPF.
PMID- 29348179
TI - Cigarette smoking and response to inhaled corticosteroids in COPD.
PMID- 29348180
TI - Persistently elevated exhaled nitric oxide fraction is associated with increased
risk of exacerbation in COPD.
AB - Preventing the occurrence of acute exacerbations of chronic obstructive pulmonary
disease (AECOPD) is a major therapeutic goal. We hypothesise that persistently
increased levels of exhaled nitric oxide (FeNO) during follow-up can identify a
group of COPD patients at higher risk of AECOPD.To test this hypothesis, we
measured FeNO levels (HypAir FeNO(r), Medisoft; Sorinnes, Belgium) prospectively
in 226 clinically stable COPD outpatients at recruitment and during follow-up (at
6 and 12 months). Patients were stratified according to the number of visits with
FeNO >=20 ppb.FeNO was <20 ppb in all three visits in 44.2% of patients, 29.6% in
visit 1 and 26.1% in visit 2 or 3. These three groups suffered progressively
higher AECOPD rates during follow-up (0.67, 0.91 and 1.42, respectively,
p<0.001). After adjusting for potential confounding variables (log-rank test),
the hazard ratio for AECOPD was higher in the latter group (1.579 (95% CI 1.049
2.378), p=0.029). Likewise, time to first moderate and severe AECOPD was shorter
in these patients. Finally, there was no relationship between FeNO levels and
circulating eosinophils.Persistent FeNO levels >=20 ppb in clinically stable COPD
outpatients are associated with a significantly higher risk of AECOPD.
PMID- 29348181
TI - Intensity of exposure to pulmonary tuberculosis determines risk of tuberculosis
infection and disease.
AB - Household contacts of pulmonary tuberculosis (TB) patients are at increased risk
of TB infection and disease. However, their risk in relation to the intensity of
exposure remains unknown.We studied smear-positive TB cases and their household
contacts in Vitoria, Brazil. We collected clinical, demographic and radiographic
information from TB cases, and obtained tuberculin skin test (TST) and
QuantiFERON-TB Gold (QFT) results from household contacts. We measured intensity
of exposure using a proximity score and sleep location in relation to the TB
index case and defined infection by TST >=10 mm or QFT >=0.35 UI.mL-1 We
ascertained secondary TB cases by reviewing local and nationwide case
registries.We included 160 TB index cases and 894 household contacts. 464 (65%)
had TB infection and 23 (2.6%) developed TB disease. Risk of TB infection and
disease increased with more intense exposures. In an adjusted analysis, the
proximity score was associated with TB disease (OR 1.61, 95% CI 1.25-2.08;
p<0.000); however, its diagnostic performance was only moderate.Intensity of
exposure increased risk of TB infection and disease among household contacts;
however, its diagnostic performance was still suboptimal. A biomarker to target
preventive therapy is urgently needed in this at-risk population.
PMID- 29348182
TI - Trends in mortality from idiopathic pulmonary fibrosis in the European Union: an
observational study of the WHO mortality database from 2001-2013.
AB - Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic
interstitial pneumonias and is characterised by progressive accumulation of scar
tissue in the lungs. The objective of this study was to describe the current
mortality rates due to IPF in Europe, based on the World Health Organization
(WHO) mortality database.We used country-level data for IPF mortality, identified
in the WHO mortality database using International Classification of Diseases 10th
Edition (ICD-10) codes, for the period 2001-2013. Joinpoint analysis was
performed to describe trends throughout the observation period.The median
mortality was 3.75 per 100 000 (interquartile range (IQR) 1.37-5.30) and 1.50 per
100 000 (IQR 0.65-2.02) for males and females, respectively. IPF mortality
increased in the majority of the European Union (EU) countries with the
exceptions of Denmark, Croatia, Austria and Romania. There was a significant
disparity in rates across Europe, in the range 0.41-12.1 per 100 000 for men and
0.24-5.63 per 100 000 for women. The most notable increases were observed in the
United Kingdom and Finland. Rates were also substantially higher in males, with
sex disparity increasing across the period.The reported IPF mortality appears to
be increasing across the EU; however, there is substantial variation in mortality
trends and overall reported mortality rates between countries.
PMID- 29348183
TI - Neurophysiological mechanisms of exertional dyspnoea in fibrotic interstitial
lung disease.
AB - Our understanding of the mechanisms of dyspnoea in fibrotic interstitial lung
disease (ILD) is incomplete. The aims of this study were two-fold: 1) to
determine whether dyspnoea intensity is better predicted by neural respiratory
drive (NRD) or neuromechanical uncoupling (NMU) of the respiratory system in
fibrotic ILD, and 2) to examine the effect of breathing 60% oxygen on NRD, NMU
and dyspnoea ratings.Fourteen patients with fibrotic ILD were included. Visit 1
comprised a familiarisation incremental cycle exercise test, Visit 2 comprised a
normoxic incremental cycling test to address Aim 1, and Visits 3 and 4 consisted
of constant-load cycling while breathing room air or 60% oxygen to address Aim 2.
Diaphragmatic electromyography (EMGdi) was used as a surrogate of NRD. NMU was
calculated as the ratio between EMGdi (%max) and tidal volume (%vital
capacity).On adjusted analysis, NMU and its constituents were all significantly
associated with dyspnoea ratings during incremental cycling, with EMGdi having
the strongest correlation. The between-treatment change in dyspnoea ratings
during constant load cycling was only correlated with change in exercise
endurance time and NMU.Dyspnoea more strongly reflected the level of EMGdi than
NMU in fibrotic ILD. However, the improvement in dyspnoea with 60% oxygen was
better predicted by improvements in NMU.
PMID- 29348184
TI - Improved identification of thrombolysis candidates amongst intermediate-risk
pulmonary embolism patients: implications for future trials.
PMID- 29348185
TI - Daily home spirometry to detect early steroid treatment effects in newly treated
pulmonary sarcoidosis.
PMID- 29348186
TI - Can YKL-40 be used as a biomarker and therapeutic target for adult asthma?
PMID- 29348187
TI - The increasing mortality of idiopathic pulmonary fibrosis: fact or fallacy?
PMID- 29348188
TI - The unmet medical need of pulmonary hypertension in idiopathic pulmonary
fibrosis.
PMID- 29348189
TI - Cancer Stem Cell Phenotypes in ER+ Breast Cancer Models Are Promoted by
PELP1/AIB1 Complexes.
AB - Proline, glutamic acid, leucine-rich protein 1 (PELP1) is overexpressed in
approximately 80% of invasive breast tumors. PELP1 dynamically shuttles between
the nucleus and cytoplasm, but is primarily nuclear in normal breast tissue.
However, altered localization of PELP1 to the cytoplasm is an oncogenic event
that promotes breast cancer initiation and progression. Herein, interacting
partners unique to cytoplasmic PELP1 and the mechanisms by which these
interactions promote oncogenic PELP1 signaling were sought. AIB1 (amplified in
breast cancer 1; also known as SRC-3 or NCOA3) was identified as a novel binding
partner of cytoplasmic PELP1 in both estrogen receptor-positive (ER+) and ER
negative cell lines. Cytoplasmic PELP1 expression elevated basal phosphorylation
levels (i.e., activation) of AIB1 at Thr24, enhanced ALDH+ tumorsphere formation,
and upregulated specific target genes independently of hormone stimulation.
Direct manipulation of AIB1 levels using shRNA abrogated cytoplasmic PELP1
induced tumorsphere formation and downregulated cytoplasmic PELP1-specific target
genes. SI-2, an AIB1 inhibitor, limited the PELP1/AIB1 interaction and decreased
cytoplasmic PELP1-induced tumorsphere formation. Similar results were observed in
a murine-derived MMTV-AIB1 tumor cell line. Furthermore, in vivo syngeneic tumor
studies revealed that PELP1 knockdown resulted in increased survival of tumor
bearing mice as compared with mice injected with control cells.Implications:
These data demonstrate that cytoplasmic PELP1/AIB1-containing complexes function
to promote advanced cancer phenotypes, including outgrowth of stem-like cells,
associated with estrogen-independent breast cancer progression. Mol Cancer Res;
16(4); 707-19. (c)2018 AACR.
PMID- 29348192
TI - Differential Contributions of Nucleus Accumbens Subregions to Cue-Guided
Risk/Reward Decision Making and Implementation of Conditional Rules.
AB - The nucleus accumbens (NAc) is a key node within corticolimbic circuitry for
guiding action selection and cost/benefit decision making in situations involving
reward uncertainty. Preclinical studies have typically assessed risk/reward
decision making using assays where decisions are guided by internally generated
representations of choice-outcome contingencies. Yet, real-life decisions are
often influenced by external stimuli that inform about likelihoods of obtaining
rewards. How different subregions of the NAc mediate decision making in such
situations is unclear. Here, we used a novel assay colloquially termed the
"Blackjack" task that models these types of situations. Male Long-Evans rats were
trained to choose between one lever that always delivered a one-pellet reward and
another that delivered four pellets with different probabilities [either 50%
(good-odds) or 12.5% (poor-odds)], which were signaled by one of two auditory
cues. Under control conditions, rats selected the large/risky option more often
on good-odds versus poor-odds trials. Inactivation of the NAc core caused
indiscriminate choice patterns. In contrast, NAc shell inactivation increased
risky choice, more prominently on poor-odds trials. Additional experiments
revealed that both subregions contribute to auditory conditional discrimination.
NAc core or shell inactivation reduced Pavlovian approach elicited by an auditory
CS+, yet shell inactivation also increased responding during presentation of a CS
. These data highlight distinct contributions for NAc subregions in decision
making and reward seeking guided by discriminative stimuli. The core is crucial
for implementation of conditional rules, whereas the shell refines reward seeking
by mitigating the allure of larger, unlikely rewards and reducing expression of
inappropriate or non-rewarded actions.SIGNIFICANCE STATEMENT Using external cues
to guide decision making is crucial for adaptive behavior. Deficits in cue-guided
behavior have been associated with neuropsychiatric disorders, such as attention
deficit hyperactivity disorder and schizophrenia, which in turn has been linked
to aberrant processing in the nucleus accumbens. However, many preclinical
studies have often assessed risk/reward decision making in the absence of
explicit cues. The current study fills that gap by using a novel task that allows
for the assessment of cue-guided risk/reward decision making in rodents. Our
findings identified distinct yet complementary roles for the medial versus
lateral portions of this nucleus that provide a broader understanding of the
differential contributions it makes to decision making and reward seeking guided
by discriminative stimuli.
PMID- 29348190
TI - Pronounced Hyperactivity, Cognitive Dysfunctions, and BDNF Dysregulation in
Dopamine Transporter Knock-out Rats.
AB - Dopamine (DA) controls many vital physiological functions and is critically
involved in several neuropsychiatric disorders such as schizophrenia and
attention deficit hyperactivity disorder. The major function of the plasma
membrane dopamine transporter (DAT) is the rapid uptake of released DA into
presynaptic nerve terminals leading to control of both the extracellular levels
of DA and the intracellular stores of DA. Here, we present a newly developed
strain of rats in which the gene encoding DAT knockout Rats (DAT-KO) has been
disrupted by using zinc finger nuclease technology. Male and female DAT-KO rats
develop normally but weigh less than heterozygote and wild-type rats and
demonstrate pronounced spontaneous locomotor hyperactivity. While striatal
extracellular DA lifetime and concentrations are significantly increased, the
total tissue content of DA is markedly decreased demonstrating the key role of
DAT in the control of DA neurotransmission. Hyperactivity of DAT-KO rats can be
counteracted by amphetamine, methylphenidate, the partial Trace Amine-Associated
Receptor 1 (TAAR1) agonist RO5203648 ((S)-4-(3,4-Dichloro-phenyl)-4,5-dihydro
oxazol-2-ylamine) and haloperidol. DAT-KO rats also demonstrate a deficit in
working memory and sensorimotor gating tests, less propensity to develop
obsessive behaviors and show strong dysregulation in frontostriatal BDNF
function. DAT-KO rats could provide a novel translational model for human
diseases involving aberrant DA function and/or mutations affecting DAT or related
regulatory mechanisms.SIGNIFICANCE STATEMENT Here, we present a newly developed
strain of rats in which the gene encoding the dopamine transporter (DAT) has been
disrupted (Dopamine Transporter Knockout rats [DAT-KO rats]). DAT-KO rats display
functional hyperdopaminergia accompanied by pronounced spontaneous locomotor
hyperactivity. Hyperactivity of DAT-KO rats can be counteracted by amphetamine,
methylphenidate, and a few other compounds exerting inhibitory action on dopamine
dependent hyperactivity. DAT-KO rats also demonstrate cognitive deficits in
working memory and sensorimotor gating tests, less propensity to develop
compulsive behaviors, and strong dysregulation in frontostriatal BDNF function.
These observations highlight the key role of DAT in the control of brain
dopaminergic transmission. DAT-KO rats could provide a novel translational model
for human diseases involving aberrant dopamine functions.
PMID- 29348193
TI - Heartbeat: Computed tomographic coronary angiography in patients with possible
angina.
PMID- 29348191
TI - Multimodal Encoding of Novelty, Reward, and Learning in the Primate Nucleus
Basalis of Meynert.
AB - Associative learning is crucial for daily function, involving a complex network
of brain regions. One region, the nucleus basalis of Meynert (NBM), is a highly
interconnected, largely cholinergic structure implicated in multiple aspects of
learning. We show that single neurons in the NBM of nonhuman primates (NHPs; n =
2 males; Macaca mulatta) encode learning a new association through spike rate
modulation. However, the power of low-frequency local field potential (LFP)
oscillations decreases in response to novel, not-yet-learned stimuli but then
increase as learning progresses. Both NBM and the dorsolateral prefrontal cortex
encode confidence in novel associations by increasing low- and high-frequency LFP
power in anticipation of expected rewards. Finally, NBM high-frequency power
dynamics are anticorrelated with spike rate modulations. Therefore, novelty,
learning, and reward anticipation are separately encoded through differentiable
NBM signals. By signaling both the need to learn and confidence in newly acquired
associations, NBM may play a key role in coordinating cortical activity
throughout the learning process.SIGNIFICANCE STATEMENT Degradation of cells in a
key brain region, the nucleus basalis of Meynert (NBM), correlates with
Alzheimer's disease and Parkinson's disease progression. To better understand the
role of this brain structure in learning and memory, we examined neural activity
in the NBM in behaving nonhuman primates while they performed a learning and
memory task. We found that single neurons in NBM encoded both salience and an
early learning, or cognitive state, whereas populations of neurons in the NBM and
prefrontal cortex encode learned state and reward anticipation. The NBM may thus
encode multiple stages of learning. These multimodal signals might be leveraged
in future studies to develop neural stimulation to facilitate different stages of
learning and memory.
PMID- 29348194
TI - Health Care Costs Associated With Incident Complications in Patients With Type 2
Diabetes in Germany.
AB - OBJECTIVE: The aim of this study is to provide reliable regression-based
estimates of costs associated with different type 2 diabetes complications.
RESEARCH DESIGN AND METHODS: We used nationwide statutory health insurance (SHI)
data from 316,220 patients with type 2 diabetes. Costs for inpatient and
outpatient care, pharmaceuticals, rehabilitation, and nonmedical aids and
appliances were assessed in the years 2013-2015. Quarterly observations are
available for each year. We estimated costs (in 2015 euro) for complications
using a generalized estimating equations model with a normal distribution
adjusted for age, sex, occurrence of different complications, and history of
complications at baseline, 2012. Two- and threefold interactions were included in
an extended model. RESULTS: The base case model estimated total costs in the
quarter of event for the example of a 60- to 69-year-old man as follows: diabetic
foot ?1,293, amputation ?14,284, retinopathy ?671, blindness ?2,933, nephropathy
?3,353, end-stage renal disease (ESRD) ?22,691, nonfatal stroke ?9,769, fatal
stroke ?11,176, nonfatal myocardial infarction (MI)/cardiac arrest (CA) ?8,035,
fatal MI/CA ?8,700, nonfatal ischemic heart disease (IHD) ?6,548, fatal IHD
?20,942, chronic heart failure ?3,912, and angina pectoris ?2,695. In the
subsequent quarters, costs ranged from ?681 for retinopathy to ?6,130 for ESRD.
CONCLUSIONS: Type 2 diabetes complications have a significant impact on total
health care costs in the SHI system, not only in the quarter of event but also in
subsequent years. Men and women from different age-groups differ in their costs
for complications. Our comprehensive estimates may support the parametrization of
diabetes models and help clinicians and policy makers to quantify the economic
burden of diabetes complications in the context of new prevention and treatment
programs.
PMID- 29348195
TI - Morbidity and Mortality in Small for Gestational Age Infants at 22 to 29 Weeks'
Gestation.
AB - OBJECTIVES: To identify the relative risks of mortality and morbidities for small
for gestational age (SGA) infants in comparison with non-SGA infants born at 22
to 29 weeks' gestation. METHODS: Data were collected (2006-2014) on 156 587
infants from 852 US centers participating in the Vermont Oxford Network. We
defined SGA as sex-specific birth weight <10th centile for gestational age (GA)
in days. Binomial generalized additive models with a thin plate spline term on GA
by SGA were used to calculate the adjusted relative risks and 95% confidence
intervals for outcomes by GA. RESULTS: Compared with non-SGA infants, the risk of
patent ductus arteriosus decreased for SGA infants in early GA and then increased
in later GA. SGA infants were also at increased risks of mortality, respiratory
distress syndrome, necrotizing enterocolitis, late-onset sepsis, severe
retinopathy of prematurity, and chronic lung disease. These risks of adverse
outcomes, however, were not homogeneous across the GA range. Early-onset sepsis
was not different between the 2 groups for the majority of GAs, although severe
intraventricular hemorrhage was decreased among SGA infants for only gestational
week 24 through week 25. CONCLUSIONS: SGA was associated with additional risks to
mortality and morbidities, but the risks differed across the GA range.
PMID- 29348196
TI - Placental Findings and Effect of Prophylactic Hydrocortisone in Extremely Preterm
Infants.
AB - OBJECTIVES: To investigate the relationship between histologic findings of the
placenta and response to early postnatal hydrocortisone treatment used to prevent
bronchopulmonary dysplasia (BPD) in extremely preterm infants. METHODS: In an
exploratory analysis of the Early Low-Dose Hydrocortisone to Improve Survival
Without Bronchopulmonary Dysplasia in Extremely Preterm Infants (PREMILOC) trial,
detailed placental analyses were performed on the basis of standardized
macroscopic and histologic examinations. Placental histology, categorized into 3
groups, was correlated to neonatal outcomes and response to hydrocortisone
treatment. RESULTS: Of 523 randomly assigned patients, 457 placentas were
analyzed. In total, 125 out of 457 (27%) placentas were classified as normal, 236
out of 457 (52%) placentas were classified as inflammatory, and 96 out of 457
(21%) placentas were classified as vascular. Placental inflammation was
associated with a significant, increased rate of BPD-free survival at 36 weeks'
postmenstrual age, independent of gestational age, treatment group, and sex
(adjusted odds ratio: 1.72, 95% confidence interval [CI]: 1.05 to 2.82, P = .03).
Regarding the response to treatment, the strongest benefit of hydrocortisone
compared with placebo was found in infants born after placental vascular disease,
with significantly more patients extubated at day 10 (risk difference: 0.32, 95%
CI: 0.08 to 0.56, P = .004) and similar positive direction on survival without
BPD (risk difference: 0.23, 95% CI: 0.00 to 0.46, P = .06). Adjusted to
gestational age and treatment groups, placental inflammation was associated with
significantly fewer patent ductus arteriosus ligation (adjusted hazard ratio:
0.58, 95% CI: 0.36 to 0.95, P = .03). Placental histology was not found to be
associated with other adverse events related to preterm birth. CONCLUSIONS: With
these findings, we confirm that early low-dose hydrocortisone confers benefits in
extremely preterm infants overall and we suggest there is a higher treatment
effect in those born after placental vascular disease.
PMID- 29348197
TI - Tackling hearing loss to improve the care of older adults.
PMID- 29348198
TI - Interleukin-10 stiffens the heart.
AB - Cardiac-resident macrophages are a diverse population of cells that have a
critical role in the pathogenesis of heart failure. A new understanding of
communication between macrophages and cardiac fibroblasts could lead to novel
therapeutic strategies for heart failure with preserved ejection function.
PMID- 29348199
TI - Origins of low-symmetry phases in asymmetric diblock copolymer melts.
AB - Cooling disordered compositionally asymmetric diblock copolymers leads to the
formation of nearly spherical particles, each containing hundreds of molecules,
which crystallize upon cooling below the order-disorder transition temperature
(TODT). Self-consistent field theory (SCFT) reveals that dispersity in the block
degrees of polymerization stabilizes various Frank-Kasper phases, including the
C14 and C15 Laves phases, which have been accessed experimentally in low-molar
mass poly(isoprene)-b-poly(lactide) (PI-PLA) diblock copolymers using thermal
processing strategies. Heating and cooling a specimen containing 15% PLA above
and below the TODT from the body-centered cubic (BCC) or C14 states regenerates
the same crystalline order established at lower temperatures. This memory effect
is also demonstrated with a specimen containing 20% PLA, which recrystallizes to
either C15 or hexagonally ordered cylinders (HEXC) upon heating and cooling. The
process-path-dependent formation of crystalline order shapes the number of
particles per unit volume, n/V, which is retained in the highly structured
disordered liquid as revealed by small-angle X-ray scattering (SAXS) experiments.
We hypothesize that symmetry breaking during crystallization is governed by the
particle number density imprinted in the liquid during ordering at lower
temperature, and this metastable liquid is kinetically constrained from
equilibrating due to prohibitively large free energy barriers for micelle fusion
and fission. Ordering at fixed n/V is enabled by facile chain exchange, which
redistributes mass as required to meet the multiple particle sizes and packing
associated with specific low-symmetry Frank-Kasper phases. This discovery exposes
universal concepts related to order and disorder in self-assembled soft
materials.
PMID- 29348200
TI - Active learning machine learns to create new quantum experiments.
AB - How useful can machine learning be in a quantum laboratory? Here we raise the
question of the potential of intelligent machines in the context of scientific
research. A major motivation for the present work is the unknown reachability of
various entanglement classes in quantum experiments. We investigate this question
by using the projective simulation model, a physics-oriented approach to
artificial intelligence. In our approach, the projective simulation system is
challenged to design complex photonic quantum experiments that produce high
dimensional entangled multiphoton states, which are of high interest in modern
quantum experiments. The artificial intelligence system learns to create a
variety of entangled states and improves the efficiency of their realization. In
the process, the system autonomously (re)discovers experimental techniques which
are only now becoming standard in modern quantum optical experiments-a trait
which was not explicitly demanded from the system but emerged through the process
of learning. Such features highlight the possibility that machines could have a
significantly more creative role in future research.
PMID- 29348201
TI - Solution structure of sperm lysin yields novel insights into molecular dynamics
of rapid protein evolution.
AB - Protein evolution is driven by the sum of different physiochemical and genetic
processes that usually results in strong purifying selection to maintain
biochemical functions. However, proteins that are part of systems under arms race
dynamics often evolve at unparalleled rates that can produce atypical biochemical
properties. In the marine mollusk abalone, lysin and vitelline envelope receptor
for lysin (VERL) are a pair of rapidly coevolving proteins that are essential for
species-specific interactions between sperm and egg. Despite extensive
biochemical characterization of lysin-including crystal structures of multiple
orthologs-it was unclear how sites under positive selection may facilitate
recognition of VERL. Using a combination of targeted mutagenesis and
multidimensional NMR, we present a high-definition solution structure of sperm
lysin from red abalone (Haliotis rufescens). Unapparent from the crystallography
data, multiple NMR-based analyses conducted in solution reveal clustering of the
N and C termini to form a nexus of 13 positively selected sites that constitute a
VERL binding interface. Evolutionary rate was found to be a significant predictor
of backbone flexibility, which may be critical for lysin bioactivity and/or
accelerated evolution. Flexible, rapidly evolving segments that constitute the
VERL binding interface were also the most distorted regions of the crystal
structure relative to what was observed in solution. While lysin has been the
subject of extensive biochemical and evolutionary analyses for more than 30
years, this study highlights the enhanced insights gained from applying NMR
approaches to rapidly evolving proteins.
PMID- 29348202
TI - Molecular characterization of latent GDF8 reveals mechanisms of activation.
AB - Growth/differentiation factor 8 (GDF8), or myostatin, negatively regulates muscle
mass. GDF8 is held in a latent state through interactions with its N-terminal
prodomain, much like TGF-beta. Using a combination of small-angle X-ray
scattering and mutagenesis, we characterized the interactions of GDF8 with its
prodomain. Our results show that the prodomain:GDF8 complex can exist in a fully
latent state and an activated or "triggered" state where the prodomain remains in
complex with the mature domain. However, these states are not reversible,
indicating the latent GDF8 is "spring-loaded." Structural analysis shows that the
prodomain:GDF8 complex adopts an "open" configuration, distinct from the latency
state of TGF-beta and more similar to the open state of Activin A and BMP9
(nonlatent complexes). We determined that GDF8 maintains similar features for
latency, including the alpha-1 helix and fastener elements, and identified a
series of mutations in the prodomain of GDF8 that alleviate latency, including
I56E, which does not require activation by the protease Tolloid. In vivo, active
GDF8 variants were potent negative regulators of muscle mass, compared with WT
GDF8. Collectively, these results help characterize the latency and activation
mechanisms of GDF8.
PMID- 29348203
TI - Infectious virus in exhaled breath of symptomatic seasonal influenza cases from a
college community.
AB - Little is known about the amount and infectiousness of influenza virus shed into
exhaled breath. This contributes to uncertainty about the importance of airborne
influenza transmission. We screened 355 symptomatic volunteers with acute
respiratory illness and report 142 cases with confirmed influenza infection who
provided 218 paired nasopharyngeal (NP) and 30-minute breath samples (coarse >5
um and fine <=5-um fractions) on days 1-3 after symptom onset. We assessed viral
RNA copy number for all samples and cultured NP swabs and fine aerosols. We
recovered infectious virus from 52 (39%) of the fine aerosols and 150 (89%) of
the NP swabs with valid cultures. The geometric mean RNA copy numbers were 3.8 *
104/30-minutes fine-, 1.2 * 104/30-minutes coarse-aerosol sample, and 8.2 * 108
per NP swab. Fine- and coarse-aerosol viral RNA were positively associated with
body mass index and number of coughs and negatively associated with increasing
days since symptom onset in adjusted models. Fine-aerosol viral RNA was also
positively associated with having influenza vaccination for both the current and
prior season. NP swab viral RNA was positively associated with upper respiratory
symptoms and negatively associated with age but was not significantly associated
with fine- or coarse-aerosol viral RNA or their predictors. Sneezing was rare,
and sneezing and coughing were not necessary for infectious aerosol generation.
Our observations suggest that influenza infection in the upper and lower airways
are compartmentalized and independent.
PMID- 29348204
TI - Tumor suppressor APC is an attenuator of spindle-pulling forces during C. elegans
asymmetric cell division.
AB - The adenomatous polyposis coli (APC) tumor suppressor has dual functions in
Wnt/beta-catenin signaling and accurate chromosome segregation and is frequently
mutated in colorectal cancers. Although APC contributes to proper cell division,
the underlying mechanisms remain poorly understood. Here we show that
Caenorhabditis elegans APR-1/APC is an attenuator of the pulling forces acting on
the mitotic spindle. During asymmetric cell division of the C. elegans zygote, a
LIN-5/NuMA protein complex localizes dynein to the cell cortex to generate
pulling forces on astral microtubules that position the mitotic spindle. We found
that APR-1 localizes to the anterior cell cortex in a Par-aPKC polarity-dependent
manner and suppresses anterior centrosome movements. Our combined cell biological
and mathematical analyses support the conclusion that cortical APR-1 reduces
force generation by stabilizing microtubule plus-ends at the cell cortex.
Furthermore, APR-1 functions in coordination with LIN-5 phosphorylation to
attenuate spindle-pulling forces. Our results document a physical basis for the
attenuation of spindle-pulling force, which may be generally used in asymmetric
cell division and, when disrupted, potentially contributes to division defects in
cancer.
PMID- 29348205
TI - Structure of the fission yeast actomyosin ring during constriction.
AB - Cell division in many eukaryotes is driven by a ring containing actin and myosin.
While much is known about the main proteins involved, the precise arrangement of
actin filaments within the contractile machinery, and how force is transmitted to
the membrane, remains unclear. Here we use cryosectioning and cryofocused ion
beam milling to gain access to cryopreserved actomyosin rings in
Schizosaccharomyces pombe for direct 3D imaging by electron cryotomography. Our
results show that straight, overlapping actin filaments, running nearly parallel
to each other and to the membrane, form a loose bundle of ~150 nm in diameter
that "saddles" the inward-bending membrane at the leading edge of the division
septum. The filaments do not make direct contact with the membrane. Our analysis
of the actin filaments reveals the variability in filament number, nearest
neighbor distances between filaments within the bundle, their distance from the
membrane, and angular distribution with respect to the membrane.
PMID- 29348206
TI - Rotational 3D printing of damage-tolerant composites with programmable mechanics.
AB - Natural composites exhibit exceptional mechanical performance that often arises
from complex fiber arrangements within continuous matrices. Inspired by these
natural systems, we developed a rotational 3D printing method that enables
spatially controlled orientation of short fibers in polymer matrices solely by
varying the nozzle rotation speed relative to the printing speed. Using this
method, we fabricated carbon fiber-epoxy composites composed of volume elements
(voxels) with programmably defined fiber arrangements, including adjacent regions
with orthogonally and helically oriented fibers that lead to nonuniform strain
and failure as well as those with purely helical fiber orientations akin to
natural composites that exhibit enhanced damage tolerance. Our approach broadens
the design, microstructural complexity, and performance space for fiber
reinforced composites through site-specific optimization of their fiber
orientation, strain, failure, and damage tolerance.
PMID- 29348207
TI - QnAs with Frank S. Bates.
PMID- 29348208
TI - Learning to make external sensory stimulus predictions using internal
correlations in populations of neurons.
AB - To compensate for sensory processing delays, the visual system must make
predictions to ensure timely and appropriate behaviors. Recent work has found
predictive information about the stimulus in neural populations early in vision
processing, starting in the retina. However, to utilize this information, cells
downstream must be able to read out the predictive information from the spiking
activity of retinal ganglion cells. Here we investigate whether a downstream cell
could learn efficient encoding of predictive information in its inputs from the
correlations in the inputs themselves, in the absence of other instructive
signals. We simulate learning driven by spiking activity recorded in salamander
retina. We model a downstream cell as a binary neuron receiving a small group of
weighted inputs and quantify the predictive information between activity in the
binary neuron and future input. Input weights change according to spike timing
dependent learning rules during a training period. We characterize the readouts
learned under spike timing-dependent synaptic update rules, finding that although
the fixed points of learning dynamics are not associated with absolute optimal
readouts they convey nearly all of the information conveyed by the optimal
readout. Moreover, we find that learned perceptrons transmit position and
velocity information of a moving-bar stimulus nearly as efficiently as optimal
perceptrons. We conclude that predictive information is, in principle, readable
from the perspective of downstream neurons in the absence of other inputs. This
suggests an important role for feedforward prediction in sensory encoding.
PMID- 29348209
TI - Influence of water and enzyme SpnF on the dynamics and energetics of the
ambimodal [6+4]/[4+2] cycloaddition.
AB - SpnF is the first monofunctional Diels-Alder/[6+4]-ase that catalyzes a reaction
leading to both Diels-Alder and [6+4] adducts through a single transition state.
The environment-perturbed transition-state sampling method has been developed to
calculate free energies, kinetic isotope effects, and quasi-classical reaction
trajectories of enzyme-catalyzed reactions and the uncatalyzed reaction in water.
Energetics calculated in this way reproduce the experiment and show that the
normal Diels-Alder transition state is stabilized by H bonds with water
molecules, while the ambimodal transition state is favored in the enzyme SpnF by
both intramolecular hydrogen bonding and hydrophobic binding. Molecular dynamics
simulations show that trajectories passing through the ambimodal transition state
bifurcate to the [6+4] adduct and the Diels-Alder adduct with a ratio of 1:1 in
the gas phase, 1:1.6 in water, and 1:11 in the enzyme. This example shows how an
enzyme acts on a vibrational time scale to steer post-transition state
trajectories toward the Diels-Alder adduct.
PMID- 29348212
TI - The 1918 flu, 100 years later.
PMID- 29348213
TI - News at a glance.
PMID- 29348214
TI - Newborn exoplanet eyed for moons and rings.
PMID- 29348210
TI - Toward dynamic structural biology: Two decades of single-molecule Forster
resonance energy transfer.
AB - Classical structural biology can only provide static snapshots of
biomacromolecules. Single-molecule Forster resonance energy transfer (smFRET)
paved the way for studying dynamics in macromolecular structures under
biologically relevant conditions. Since its first implementation in 1996, smFRET
experiments have confirmed previously hypothesized mechanisms and provided new
insights into many fundamental biological processes, such as DNA maintenance and
repair, transcription, translation, and membrane transport. We review 22 years of
contributions of smFRET to our understanding of basic mechanisms in biochemistry,
molecular biology, and structural biology. Additionally, building on current
state-of-the-art implementations of smFRET, we highlight possible future
directions for smFRET in applications such as biosensing, high-throughput
screening, and molecular diagnostics.
PMID- 29348215
TI - 'Liquid biopsy' for cancer promises early detection.
PMID- 29348211
TI - Membrane protein insertion through a mitochondrial beta-barrel gate.
AB - The biogenesis of mitochondria, chloroplasts, and Gram-negative bacteria requires
the insertion of beta-barrel proteins into the outer membranes. Homologous Omp85
proteins are essential for membrane insertion of beta-barrel precursors. It is
unknown if precursors are threaded through the Omp85-channel interior and exit
laterally or if they are translocated into the membrane at the Omp85-lipid
interface. We have mapped the interaction of a precursor in transit with the
mitochondrial Omp85-channel Sam50 in the native membrane environment. The
precursor is translocated into the channel interior, interacts with an internal
loop, and inserts into the lateral gate by beta-signal exchange. Transport
through the Omp85-channel interior followed by release through the lateral gate
into the lipid phase may represent a basic mechanism for membrane insertion of
beta-barrel proteins.
PMID- 29348216
TI - Tamed immune reaction aids pregnancy.
PMID- 29348217
TI - Tensions flare over electric fishing in European waters.
PMID- 29348218
TI - Rochester roiled by fallout from sexual harassment case.
PMID- 29348219
TI - Are algorithms good judges?
PMID- 29348220
TI - The believer.
PMID- 29348221
TI - Assessing nature's contributions to people.
PMID- 29348222
TI - The art of manufacturing molecules.
PMID- 29348223
TI - Quantum liquids get thin.
PMID- 29348224
TI - A bacterial coat that is not pure cotton.
PMID- 29348225
TI - Taking down defenses to improve vaccines.
PMID- 29348226
TI - Remote control of nanoscale devices.
PMID- 29348227
TI - Ben Barres (1954-2017).
PMID- 29348228
TI - The pitfalls of taking science to the public.
PMID- 29348229
TI - Vaccine mandates in France will save lives.
PMID- 29348230
TI - Have your momos and eat them, too.
PMID- 29348232
TI - A self-assembled nanoscale robotic arm controlled by electric fields.
AB - The use of dynamic, self-assembled DNA nanostructures in the context of
nanorobotics requires fast and reliable actuation mechanisms. We therefore
created a 55-nanometer-by-55-nanometer DNA-based molecular platform with an
integrated robotic arm of length 25 nanometers, which can be extended to more
than 400 nanometers and actuated with externally applied electrical fields.
Precise, computer-controlled switching of the arm between arbitrary positions on
the platform can be achieved within milliseconds, as demonstrated with single
pair Forster resonance energy transfer experiments and fluorescence microscopy.
The arm can be used for electrically driven transport of molecules or
nanoparticles over tens of nanometers, which is useful for the control of
photonic and plasmonic processes. Application of piconewton forces by the robot
arm is demonstrated in force-induced DNA duplex melting experiments.
PMID- 29348231
TI - Genome-wide identification of interferon-sensitive mutations enables influenza
vaccine design.
AB - In conventional attenuated viral vaccines, immunogenicity is often suboptimal.
Here we present a systematic approach for vaccine development that eliminates
interferon (IFN)-modulating functions genome-wide while maintaining virus
replication fitness. We applied a quantitative high-throughput genomics system to
influenza A virus that simultaneously measured the replication fitness and IFN
sensitivity of mutations across the entire genome. By incorporating eight IFN
sensitive mutations, we generated a hyper-interferon-sensitive (HIS) virus as a
vaccine candidate. HIS virus is highly attenuated in IFN-competent hosts but able
to induce transient IFN responses, elicits robust humoral and cellular immune
responses, and provides protection against homologous and heterologous viral
challenges. Our approach, which attenuates the virus and promotes immune
responses concurrently, is broadly applicable for vaccine development against
other pathogens.
PMID- 29348233
TI - Hydraulic fracturing volume is associated with induced earthquake productivity in
the Duvernay play.
AB - A sharp increase in the frequency of earthquakes near Fox Creek, Alberta, began
in December 2013 in response to hydraulic fracturing. Using a hydraulic
fracturing database, we explore relationships between injection parameters and
seismicity response. We show that induced earthquakes are associated with
completions that used larger injection volumes (104 to 105 cubic meters) and that
seismic productivity scales linearly with injection volume. Injection pressure
and rate have an insignificant association with seismic response. Further
findings suggest that geological factors play a prominent role in seismic
productivity, as evidenced by spatial correlations. Together, volume and
geological factors account for ~96% of the variability in the induced earthquake
rate near Fox Creek. This result is quantified by a seismogenic index-modified
frequency-magnitude distribution, providing a framework to forecast induced
seismicity.
PMID- 29348234
TI - Chiromagnetic nanoparticles and gels.
AB - Chiral inorganic nanostructures have high circular dichroism, but real-time
control of their optical activity has so far been achieved only by irreversible
chemical changes. Field modulation is a far more desirable path to chiroptical
devices. We hypothesized that magnetic field modulation can be attained for
chiral nanostructures with large contributions of the magnetic transition dipole
moments to polarization rotation. We found that dispersions and gels of
paramagnetic Co3O4 nanoparticles with chiral distortions of the crystal lattices
exhibited chiroptical activity in the visible range that was 10 times as strong
as that of nonparamagnetic nanoparticles of comparable size. Transparency of the
nanoparticle gels to circularly polarized light beams in the ultraviolet range
was reversibly modulated by magnetic fields. These phenomena were also observed
for other nanoscale metal oxides with lattice distortions from imprinted amino
acids and other chiral ligands. The large family of chiral ceramic nanostructures
and gels can be pivotal for new technologies and knowledge at the nexus of
chirality and magnetism.
PMID- 29348235
TI - Digitization of multistep organic synthesis in reactionware for on-demand
pharmaceuticals.
AB - Chemical manufacturing is often done at large facilities that require a sizable
capital investment and then produce key compounds for a finite period. We present
an approach to the manufacturing of fine chemicals and pharmaceuticals in a self
contained plastic reactionware device. The device was designed and constructed by
using a chemical to computer-automated design (ChemCAD) approach that enables the
translation of traditional bench-scale synthesis into a platform-independent
digital code. This in turn guides production of a three-dimensional printed
device that encloses the entire synthetic route internally via simple operations.
We demonstrate the approach for the gamma-aminobutyric acid receptor agonist, (+/
)-baclofen, establishing a concept that paves the way for the local manufacture
of drugs outside of specialist facilities.
PMID- 29348236
TI - A global atlas of the dominant bacteria found in soil.
AB - The immense diversity of soil bacterial communities has stymied efforts to
characterize individual taxa and document their global distributions. We analyzed
soils from 237 locations across six continents and found that only 2% of
bacterial phylotypes (~500 phylotypes) consistently accounted for almost half of
the soil bacterial communities worldwide. Despite the overwhelming diversity of
bacterial communities, relatively few bacterial taxa are abundant in soils
globally. We clustered these dominant taxa into ecological groups to build the
first global atlas of soil bacterial taxa. Our study narrows down the immense
number of bacterial taxa to a "most wanted" list that will be fruitful targets
for genomic and cultivation-based efforts aimed at improving our understanding of
soil microbes and their contributions to ecosystem functioning.
PMID- 29348237
TI - Improving refugee integration through data-driven algorithmic assignment.
AB - Developed democracies are settling an increased number of refugees, many of whom
face challenges integrating into host societies. We developed a flexible data
driven algorithm that assigns refugees across resettlement locations to improve
integration outcomes. The algorithm uses a combination of supervised machine
learning and optimal matching to discover and leverage synergies between refugee
characteristics and resettlement sites. The algorithm was tested on historical
registry data from two countries with different assignment regimes and refugee
populations, the United States and Switzerland. Our approach led to gains of
roughly 40 to 70%, on average, in refugees' employment outcomes relative to
current assignment practices. This approach can provide governments with a
practical and cost-efficient policy tool that can be immediately implemented
within existing institutional structures.
PMID- 29348239
TI - From parade ground to PI.
PMID- 29348238
TI - Phosphoethanolamine cellulose: A naturally produced chemically modified
cellulose.
AB - Cellulose is a major contributor to the chemical and mechanical properties of
plants and assumes structural roles in bacterial communities termed biofilms. We
find that Escherichia coli produces chemically modified cellulose that is
required for extracellular matrix assembly and biofilm architecture. Solid-state
nuclear magnetic resonance spectroscopy of the intact and insoluble material
elucidates the zwitterionic phosphoethanolamine modification that had evaded
detection by conventional methods. Installation of the phosphoethanolamine group
requires BcsG, a proposed phosphoethanolamine transferase, with biofilm-promoting
cyclic diguanylate monophosphate input through a BcsE-BcsF-BcsG transmembrane
signaling pathway. The bcsEFG operon is present in many bacteria, including
Salmonella species, that also produce the modified cellulose. The discovery of
phosphoethanolamine cellulose and the genetic and molecular basis for its
production offers opportunities to modulate its production in bacteria and
inspires efforts to biosynthetically engineer alternatively modified cellulosic
materials.
PMID- 29348241
TI - Meet the First Authors.
PMID- 29348242
TI - Anthracycline Cardiotoxicity: Worrisome Enough to Have You Quaking?
PMID- 29348240
TI - Snf1-RELATED KINASE1-Controlled C/S1-bZIP Signaling Activates Alternative
Mitochondrial Metabolic Pathways to Ensure Plant Survival in Extended Darkness.
AB - Sustaining energy homeostasis is of pivotal importance for all living organisms.
In Arabidopsis thaliana, evolutionarily conserved SnRK1 kinases (Snf1-RELATED
KINASE1) control metabolic adaptation during low energy stress. To unravel
starvation-induced transcriptional mechanisms, we performed transcriptome studies
of inducible knockdown lines and found that S1-basic leucine zipper transcription
factors (S1-bZIPs) control a defined subset of genes downstream of SnRK1. For
example, S1-bZIPs coordinate the expression of genes involved in branched-chain
amino acid catabolism, which constitutes an alternative mitochondrial respiratory
pathway that is crucial for plant survival during starvation. Molecular analyses
defined S1-bZIPs as SnRK1-dependent regulators that directly control
transcription via binding to G-box promoter elements. Moreover, SnRK1 triggers
phosphorylation of group C-bZIPs and the formation of C/S1-heterodimers and,
thus, the recruitment of SnRK1 directly to target promoters. Subsequently, the
C/S1-bZIP-SnRK1 complex interacts with the histone acetylation machinery to
remodel chromatin and facilitate transcription. Taken together, this work reveals
molecular mechanisms underlying how energy deprivation is transduced to reprogram
gene expression, leading to metabolic adaptation upon stress.
PMID- 29348243
TI - Improving Cell Production Techniques to Enhance Autologous Cell Therapy.
PMID- 29348244
TI - Branch Point Smooth Muscle Cells Highlighted by Novel Lineage Tracking Approach.
PMID- 29348245
TI - Induced Pluripotent Stem Cells Derived Extracellular Vesicles: A Potential
Therapy for Cardiac Repair.
PMID- 29348247
TI - Scot Matkovich: Keep on Keeping on.
PMID- 29348246
TI - Global Overview of the Transnational Alliance for Regenerative Therapies in
Cardiovascular Syndromes (TACTICS) Recommendations: A Comprehensive Series of
Challenges and Priorities of Cardiovascular Regenerative Medicine.
PMID- 29348248
TI - Texas Heart Institute International Symposium on Cardiovascular Regenerative
Medicine.
PMID- 29348249
TI - The (Translational) Road Less Traveled.
PMID- 29348250
TI - T4 Translational Moonshot: Making Cardiovascular Discoveries Work for Everyone.
PMID- 29348252
TI - Translational Research in Cardiovascular Repair: A Call for a Paradigm Shift.
AB - The international consortium TACTICS (Transnational Alliance for Regenerative
Therapies in Cardiovascular Syndromes) has recently addressed key priorities in
the field of cell-based therapy for cardiac repair, identifying the efficacy of
translational research as one of the main challenges to ultimately improve the
quality of life of patients with ischemic disease. Much of the controversy and
confusion surrounding cardiac regenerative therapy stems from insufficient rigor
in the conduct of preclinical studies, and there is an increasing recognition of
a number of problems that undermine its quality that may contribute to
translational failure. Here, we introduce well defined stages for preclinical
research, and put forth proposals that should promote more rigorous preclinical
work, in an effort to improve its quality and translatability. To augment the
utility of preclinical research and its translation, it is necessary to (1)
improve the quality of preclinical research, (2) promote collaborative efforts,
and (3) enhance the sharing of knowledge and protocols. In particular,
confirmatory (stage III) preclinical studies should be considered as a preamble
to clinical studies and therefore must adhere to their standards of quality
(including internal validity, standardization of protocols, and multicenter
design). To increase transparency and minimize bias, these studies should be
prospectively registered in an independent, open database. Ultimately, these
recommendations should be implemented in the daily routine of investigators and
in the policies of institutions, journals, and funding agencies.
PMID- 29348251
TI - Reducing Cardiovascular Disparities Through Community-Engaged Implementation
Research: A National Heart, Lung, and Blood Institute Workshop Report.
AB - Cardiovascular disparities remain pervasive in the United States. Unequal disease
burden is evident among population groups based on sex, race, ethnicity,
socioeconomic status, educational attainment, nativity, or geography. Despite the
significant declines in cardiovascular disease mortality rates in all demographic
groups during the last 50 years, large disparities remain by sex, race,
ethnicity, and geography. Recent data from modeling studies, linked micromap
plots, and small-area analyses also demonstrate prominent variation in
cardiovascular disease mortality rates across states and counties, with an
especially high disease burden in the southeastern United States and Appalachia.
Despite these continued disparities, few large-scale intervention studies have
been conducted in these high-burden populations to examine the feasibility of
reducing or eliminating cardiovascular disparities. To address this challenge, on
June 22 and 23, 2017, the National Heart, Lung, and Blood Institute convened
experts from a broad range of biomedical, behavioral, environmental,
implementation, and social science backgrounds to summarize the current state of
knowledge of cardiovascular disease disparities and propose intervention
strategies aligned with the National Heart, Lung, and Blood Institute mission.
This report presents the themes, challenges, opportunities, available resources,
and recommended actions discussed at the workshop.
PMID- 29348255
TI - Hypertension and Atrial Fibrillation: Doubts and Certainties From Basic and
Clinical Studies.
AB - Hypertension and atrial fibrillation (AF) are 2 important public health
priorities. Their prevalence is increasing worldwide, and the 2 conditions often
coexist in the same patient. Hypertension and AF are strikingly related to an
excess risk of cardiovascular disease and death. Hypertension ultimately
increases the risk of AF, and because of its high prevalence in the population,
it accounts for more cases of AF than other risk factors. Among patients with
established AF, hypertension is present in about 60% to 80% of individuals.
Despite the well-known association between hypertension and AF, several
pathogenetic mechanisms underlying the higher risk of AF in hypertensive patients
are still incompletely known. From an epidemiological standpoint, it is unclear
whether the increasing risk of AF with blood pressure (BP) is linear or
threshold. It is uncertain whether an intensive control of BP or the use of
specific antihypertensive drugs, such as those inhibiting the renin-angiotensin
aldosterone system, reduces the risk of subsequent AF in hypertensive patients in
sinus rhythm. Finally, in spite of the observational evidence suggesting a
progressive relation between BP levels and the risk of thromboembolism and
bleeding in patients with hypertension and AF, the extent to which BP should be
lowered in these patients, including those who undergo catheter ablation, remains
uncertain. This article summarizes the main basic mechanisms through which
hypertension is believed to promote AF. It also explores epidemiological data
supporting an evolutionary pathway from hypertension to AF, including the
emerging evidence favoring an intensive BP control or the use of drugs, which
inhibit the renin-angiotensin-aldosterone system to reduce the risk of AF.
Finally, it examines the impact of non-vitamin K antagonist oral anticoagulants
compared with warfarin in relation to hypertension.
PMID- 29348254
TI - Circulating Platelets as Mediators of Immunity, Inflammation, and Thrombosis.
AB - Platelets, non-nucleated blood components first described over 130 years ago, are
recognized as the primary cell regulating hemostasis and thrombosis. The vascular
importance of platelets has been attributed to their essential role in
thrombosis, mediating myocardial infarction, stroke, and venous thromboembolism.
Increasing knowledge on the platelets' role in the vasculature has led to many
advances in understanding not only how platelets interact with the vessel wall
but also how they convey changes in the environment to other circulating cells.
In addition to their well-described hemostatic function, platelets are active
participants in the immune response to microbial organisms and foreign
substances. Although incompletely understood, the immune role of platelets is a
delicate balance between its pathogenic response and its regulation of thrombotic
and hemostatic functions. Platelets mediate complex vascular homeostasis via
specific receptors and granule release, RNA transfer, and mitochondrial secretion
that subsequently regulates hemostasis and thrombosis, infection, and innate and
adaptive immunity.
PMID- 29348253
TI - Multifunctional Role of Chymase in Acute and Chronic Tissue Injury and
Remodeling.
AB - Chymase is the most efficient Ang II (angiotensin II)-forming enzyme in the human
body and has been implicated in a wide variety of human diseases that also
implicate its many other protease actions. Largely thought to be the product of
mast cells, the identification of other cellular sources including cardiac
fibroblasts and vascular endothelial cells demonstrates a more widely dispersed
production and distribution system in various tissues. Furthermore, newly
emerging evidence for its intracellular presence in cardiomyocytes and smooth
muscle cells opens an entirely new compartment of chymase-mediated actions that
were previously thought to be limited to the extracellular space. This review
illustrates how these multiple chymase-mediated mechanisms of action can explain
the residual risk in clinical trials of cardiovascular disease using conventional
renin-angiotensin system blockade.
PMID- 29348257
TI - Global sexual health education: STIF in Zambia.
PMID- 29348259
TI - Thrombectomy stroke centers: The current threat to regionalizing stroke care.
PMID- 29348258
TI - High-risk behaviour and HIV infection risk among non-local men who have sex with
men with less than a single year's residence in urban centres: a multicentre
cross-sectional study from China.
AB - OBJECTIVES: Traditionally, subjects' migration status has usually been defined on
the basis of their registered residency status. We attempted to redefine
migration based on the duration of residency in their cities of migration and to
explore more precisely the impact of migration on HIV infection risk in men who
have sex with men (MSM). METHODS: A multisite cross-sectional study was conducted
during 2012-2013 in seven Chinese cities. Questionnaire surveys were conducted
and blood was drawn to test for antibodies to HIV, syphilis and herpes simplex
virus-2 (HSV-2). MSM who were unregistered local residents and had resided in
their cities of migration for <=1 or >1 year were defined as migrant MSM, or
transitional MSM, respectively. RESULTS: Compared with transitional MSM and local
MSM, migrant MSM had poorer HIV knowledge and higher rates of high-risk
behaviour, including earlier sexual debut, multiple sexual partners,
participation in commercial sex and recreational drug use. Multivariate logistic
regression analysis showed that HIV prevalence among migrant MSM was higher than
local MSM (p<0.05). This relationship, however, did not hold for transitional MSM
and local MSM (p>0.05). Male sex work, recreational drug use, syphilis infection
and HSV-2 infection were independently associated with HIV infection among
migrant MSM. CONCLUSIONS: Non-local MSM with shorter residence were at greater
risk of HIV acquisition. More focus should be placed on HIV behavioural
interventions targeting non-local MSM with temporary residence.
PMID- 29348256
TI - Flavonoids, Dairy Foods, and Cardiovascular and Metabolic Health: A Review of
Emerging Biologic Pathways.
AB - A growing body of nutritional science highlights the complex mechanisms and
pleiotropic pathways of cardiometabolic effects of different foods. Among these,
some of the most exciting advances are occurring in the area of flavonoids,
bioactive phytochemicals found in plant foods; and in the area of dairy,
including milk, yogurt, and cheese. Many of the relevant ingredients and
mechanistic pathways are now being clarified, shedding new light on both the
ingredients and the pathways for how diet influences health and well-being.
Flavonoids, for example, have effects on skeletal muscle, adipocytes, liver, and
pancreas, and myocardial, renal, and immune cells, for instance, related to 5'
monophosphate-activated protein kinase phosphorylation, endothelial NO synthase
activation, and suppression of NF-kappaB (nuclear factor-kappaB) and TLR4 (toll
like receptor 4). Effects of dairy are similarly complex and may be mediated by
specific amino acids, medium-chain and odd-chain saturated fats, unsaturated
fats, branched-chain fats, natural trans fats, probiotics, vitamin K1/K2, and
calcium, as well as by processing such as fermentation and homogenization. These
characteristics of dairy foods influence diverse pathways including related to
mammalian target of rapamycin, silent information regulator transcript-1,
angiotensin-converting enzyme, peroxisome proliferator-activated receptors,
osteocalcin, matrix glutamate protein, hepatic de novo lipogenesis, hepatic and
adipose fatty acid oxidation and inflammation, and gut microbiome interactions
such as intestinal integrity and endotoxemia. The complexity of these emerging
pathways and corresponding biological responses highlights the rapid advances in
nutritional science and the continued need to generate robust empirical evidence
on the mechanistic and clinical effects of specific foods.
PMID- 29348260
TI - The Canadian Preterm Birth Network: a study protocol for improving outcomes for
preterm infants and their families.
AB - BACKGROUND: Preterm birth (birth before 37 wk of gestation) occurs in about 8% of
pregnancies in Canada and is associated with high mortality and morbidity rates
that substantially affect infants, their families and the health care system. Our
overall goal is to create a transdisciplinary platform, the Canadian Preterm
Birth Network (CPTBN), where investigators, stakeholders and families will work
together to improve childhood outcomes of preterm neonates. METHODS: Our national
cohort will include 24 maternal-fetal/obstetrical units, 31 neonatal intensive
care units and 26 neonatal follow-up programs across Canada with planned linkages
to provincial health information systems. Three broad clusters of projects will
be undertaken. Cluster 1 will focus on quality-improvement efforts that use the
Evidence-based Practice for Improving Quality method to evaluate information from
the CPTBN database and review the current literature, then identify potentially
better health care practices and implement identified strategies. Cluster 2 will
assess the impact of current practices and practice changes in maternal,
perinatal and neonatal care on maternal, neonatal and neurodevelopmental
outcomes. Cluster 3 will evaluate the effect of preterm birth on babies, their
families and the health care system by integrating CPTBN data, parent feedback,
and national and provincial database information in order to identify areas where
more parental support is needed, and also generate robust estimates of resource
use, cost and cost-effectiveness around preterm neonatal care. INTERPRETATION:
These collaborative efforts will create a flexible, transdisciplinary, evaluable
and informative research and quality-improvement platform that supports programs,
projects and partnerships focused on improving outcomes of preterm neonates.
PMID- 29348262
TI - Dawn of a New Era for Stroke Treatment: Implications of the DAWN Study for Acute
Stroke Care and Stroke Systems of Care.
PMID- 29348261
TI - Complement Receptor C5aR1 Plays an Evolutionarily Conserved Role in Successful
Cardiac Regeneration.
AB - BACKGROUND: Defining conserved molecular pathways in animal models of successful
cardiac regeneration could yield insight into why adult mammals have inadequate
cardiac regeneration after injury. Insight into the transcriptomic landscape of
early cardiac regeneration from model organisms will shed light on evolutionarily
conserved pathways in successful cardiac regeneration. METHODS: Here we describe
a cross-species transcriptomic screen in 3 model organisms for cardiac
regeneration: axolotl, neonatal mice, and zebrafish. Apical resection to remove
~10% to 20% of ventricular mass was carried out in these model organisms. RNA
sequencing analysis was performed on the hearts harvested at 3 time points: 12,
24, and 48 hours after resection. Sham surgery was used as internal control.
RESULTS: Genes associated with inflammatory processes were found to be
upregulated in a conserved manner. Complement receptors (activated by complement
components, part of the innate immune system) were found to be highly upregulated
in all 3 species. This approach revealed induction of gene expression for
complement 5a receptor 1 in the regenerating hearts of zebrafish, axolotls, and
mice. Inhibition of complement 5a receptor 1 significantly attenuated the
cardiomyocyte proliferative response to heart injury in all 3 species.
Furthermore, after left ventricular apical resection, the cardiomyocyte
proliferative response was diminished in mice with genetic deletion of complement
5a receptor 1. CONCLUSIONS: These data reveal that activation of complement 5a
receptor 1 mediates an evolutionarily conserved response that promotes
cardiomyocyte proliferation after cardiac injury and identify complement pathway
activation as a common pathway of successful heart regeneration.
PMID- 29348263
TI - Phosphoinositide 3-Kinase Gamma Inhibition Protects From Anthracycline
Cardiotoxicity and Reduces Tumor Growth.
AB - BACKGROUND: Anthracyclines, such as doxorubicin (DOX), are potent anticancer
agents for the treatment of solid tumors and hematologic malignancies. However,
their clinical use is hampered by cardiotoxicity. This study sought to
investigate the role of phosphoinositide 3-kinase gamma (PI3Kgamma) in DOX
induced cardiotoxicity and the potential cardioprotective and anticancer effects
of PI3Kgamma inhibition. METHODS: Mice expressing a kinase-inactive PI3Kgamma or
receiving PI3Kgamma-selective inhibitors were subjected to chronic DOX treatment.
Cardiac function was analyzed by echocardiography, and DOX-mediated signaling was
assessed in whole hearts or isolated cardiomyocytes. The dual cardioprotective
and antitumor action of PI3Kgamma inhibition was assessed in mouse mammary tumor
models. RESULTS: PI3Kgamma kinase-dead mice showed preserved cardiac function
after chronic low-dose DOX treatment and were protected against DOX-induced
cardiotoxicity. The beneficial effects of PI3Kgamma inhibition were causally
linked to enhanced autophagic disposal of DOX-damaged mitochondria. Consistently,
either pharmacological or genetic blockade of autophagy in vivo abrogated the
resistance of PI3Kgamma kinase-dead mice to DOX cardiotoxicity. Mechanistically,
PI3Kgamma was triggered in DOX-treated hearts, downstream of Toll-like receptor
9, by the mitochondrial DNA released by injured organelles and contained in
autolysosomes. This autolysosomal PI3Kgamma/Akt/mTOR/Ulk1 signaling provided
maladaptive feedback inhibition of autophagy. PI3Kgamma blockade in models of
mammary gland tumors prevented DOX-induced cardiac dysfunction and concomitantly
synergized with the antitumor action of DOX by unleashing anticancer immunity.
CONCLUSIONS: Blockade of PI3Kgamma may provide a dual therapeutic advantage in
cancer therapy by simultaneously preventing anthracyclines cardiotoxicity and
reducing tumor growth.
PMID- 29348264
TI - Employment among Patients Starting Dialysis in the United States.
AB - BACKGROUND AND OBJECTIVES: Patients with ESRD face significant challenges to
remaining employed. It is unknown when in the course of kidney disease patients
stop working. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We examined
employment trends over time among patients ages 18-54 years old who initiated
dialysis in the United States between 1996 and 2013 from a national ESRD
registry. We compared unadjusted trends in employment at the start of dialysis
and 6 months before ESRD and used linear probability models to estimate changes
in employment over time after adjusting for patient characteristics and local
unemployment rates in the general population. We also examined employment among
selected vulnerable patient populations and changes in employment in the 6 months
preceding dialysis initiation. RESULTS: Employment was low among patients
starting dialysis throughout the study period at 23%-24%, and 38% of patients who
were employed 6 months before ESRD stopped working by dialysis initiation.
However, after adjusting for observed characteristics, the probability of
employment increased over time; patients starting dialysis between 2008 and 2013
had a 4.7% (95% confidence interval, 4.3% to 5.1%) increase in the absolute
probability of employment at the start of dialysis compared with patients
starting dialysis between 1996 and 2001. Black and Hispanic patients were less
likely to be employed than other patients starting dialysis, but this gap
narrowed during the study period. CONCLUSIONS: Although working-aged patients in
the United States starting dialysis have experienced increases in the adjusted
probability of employment over time, employment at the start of dialysis has
remained low.
PMID- 29348265
TI - Employment among Patients on Dialysis: An Unfulfilled Promise.
PMID- 29348266
TI - Dopamine Receptor Agonist Treatment of Idiopathic Dystonia: A Reappraisal in
Humans and Mice.
AB - Although dystonia is often associated with abnormal dopamine neurotransmission,
dopaminergic drugs are not currently used to treat dystonia because there is a
general view that dopaminergic drugs are ineffective. However, there is little
conclusive evidence to support or refute this assumption. Therefore, to assess
the therapeutic potential of these compounds, we analyzed results from multiple
trials of dopamine receptor agonists in patients with idiopathic dystonias and
also tested the efficacy of dopamine receptor agonists in a mouse model of
generalized dystonia. Our results suggest that dopamine receptor agonists were
effective in some, but not all, patients tested. Further, the mixed D1/D2
dopamine receptor agonist apomorphine was apparently more effective than subtype
selective D2 dopamine receptor agonists. However, rigorously controlled trials
are still needed. In a mouse model of dystonia, a selective D1 dopamine receptor
agonist was not effective while a selective D2 dopamine receptor had modest
efficacy. However, when combined, these receptor-selective agonists acted
synergistically to ameliorate the dystonia. Coactivation of D1 and D2 dopamine
receptors using apomorphine or by increasing extracellular concentrations of
dopamine was also effective. Thus, results from both clinical trials and tests in
mice suggest that coactivation of D1 and D2 dopamine receptors may be an
effective therapeutic strategy in some patients. These results support a
reconsideration of dopamine receptors as targets for the treatment of dystonia,
particularly because recent genetic and diagnostic advances may facilitate the
identification of the subtypes of dystonia patients who respond and those who do
not.
PMID- 29348268
TI - Is the Quest for Signaling Bias Worth the Effort?
AB - The question of whether signaling bias is a viable discovery strategy for drug
therapy is discussed as a value proposition. On the positive side, bias is easily
identified and quantified in simple in vitro functional assays with little
resource expenditure. However, there are valid pharmacological reasons why these
in vitro bias numbers may not accurately translate to in vivo therapeutic systems
making the expectation of direct correspondence of in vitro bias to in vivo
systems a problematic process. Presently, in vitro bias is used simply as a means
to identify unique molecules to be advanced to more complex therapeutic assays
but from this standpoint alone, the value proposition lies far to the positive.
However, pharmacological attention needs to be given to the translational gap to
reduce inevitable and costly attrition in biased molecule progression.
PMID- 29348267
TI - Toll-Like Receptor 9-Dependent AMPKalpha Activation Occurs via TAK1 and
Contributes to RhoA/ROCK Signaling and Actin Polymerization in Vascular Smooth
Muscle Cells.
AB - Traditionally, Toll-like receptor 9 (TLR9) signals through an MyD88-dependent
cascade that results in proinflammatory gene transcription. Recently, it was
reported that TLR9 also participates in a stress tolerance signaling cascade in
nonimmune cells. In this noncanonical pathway, TLR9 binds to and inhibits
sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2 (SERCA2), modulating
intracellular calcium handling, and subsequently resulting in the activation of
5'-AMP-activated protein kinase alpha (AMPKalpha). We have previously reported
that TLR9 causes increased contraction in isolated arteries; however, the
mechanisms underlying this vascular dysfunction need to be further clarified.
Therefore, we hypothesized that noncanonical TLR9 signaling was also present in
vascular smooth muscle cells (VSMCs) and that it mediates enhanced contractile
responses through SERCA2 inhibition. To test these hypotheses, aortic microsomes,
aortic VSMCs, and isolated arteries from male Sprague-Dawley rats were incubated
with vehicle or TLR9 agonist (ODN2395). Despite clear AMPKalpha activation after
treatment with ODN2395, SERCA2 activity was unaffected. Alternatively, ODN2395
caused the phosphorylation of AMPKalpha via transforming growth factor beta
activated kinase 1 (TAK1), a kinase involved in TLR9 inflammatory signaling.
Downstream, we hypothesized that that TLR9 activation of AMPKalpha may be
important in mediating actin cytoskeleton reorganization. ODN2395 significantly
increased the filamentous-to-globular actin ratio, as well as indices of RhoA/Rho
associated protein kinase (ROCK) activation, with the latter being prevented by
AMPKalpha inhibition. In conclusion, AMPKalpha phosphorylation after TLR9
activation in VSMCs appears to be an extension of traditional inflammatory
signaling via TAK1, as opposed to SERCA2 inhibition and the noncanonical pathway.
Nonetheless, TLR9-AMPKalpha signaling can mediate VSMC function via RhoA/ROCK
activation and actin polymerization.
PMID- 29348269
TI - Management of incidental adrenal tumours.
PMID- 29348270
TI - Hyperpigmentation in the skin folds.
PMID- 29348271
TI - Intratumoral Payload Concentration Correlates with the Activity of Antibody-Drug
Conjugates.
AB - Antibody-drug conjugates (ADC) have become important scaffolds for targeted
cancer therapies. However, ADC exposure-response correlation is not well
characterized. We demonstrated that intratumor payload exposures correlated well
with the corresponding efficacies of several disulfide-linked ADCs, bearing an
DNA alkylating agent, pyrrolo[2,1-c][1,4]benzodiazepine-dimer (PBD), in HER2
expressing xenograft models. The correlation suggests that a threshold
concentration of intratumor payload is required to support sustained efficacy and
an ADC can deliver an excessive level of payload to tumors that does not enhance
efficacy ("Plateau" effect). In contrast to tumor PBD concentrations, related
assessments of systemic exposures, plasma stability, and drug-to-antibody ratio
changes of related ADCs did not consistently rationalize the observed ADC
efficacies. A minimal efficacious dose could be determined by ADC dose
fractionation studies in the xenograft models. Mechanistic investigations
revealed that both linker immolation and linker disulfide stability are the key
factors that determine intratumor PBD concentrations. Overall, this study
demonstrates how a linker design can impact ADC efficacy and that the intratumor
exposure of a payload drug as the molecular mechanism quantitatively correlate
with and predict the antitumor efficacy of ADCs. Mol Cancer Ther; 17(3); 677-85.
(c)2018 AACR.
PMID- 29348273
TI - Correction: optic disc swelling in a patient with tuberculous meningitis: a
diagnostic challenge.
PMID- 29348272
TI - Use of Computer Technology During Family-Centered Rounds: A Qualitative Study of
Parent Perspectives.
AB - OBJECTIVES: Physicians often use computer technologies to assist in work
activities, including family-centered rounds (FCR), but little is known about the
attitudes of families on the use of these technologies. We aimed to describe
these perceptions on the presence and use of computer technologies during FCR.
METHODS: We conducted observations of FCR from a parent's visual perspective to
"see what they see." This was followed by in-depth interviews with the families
of patients admitted to the hospitalist service at our institution to describe
their experience with the use of computer technology by the medical team during
FCR. RESULTS: From the analysis of 31 individual interview transcripts, our
research team identified the following 4 themes: (1) technology serves a purpose
during FCR; (2) to view data in real time; (3) do not lose the human connection;
and (4) transparency is valued. Thirty-eight observations showed broad use of
computer technologies by the medical team. Devices were used to provide data that
would educate the family; however, the devices were often placed between the
medical team and family, creating a physical barrier. CONCLUSIONS: Families
recognized the benefit of computer technologies in the care of their child and
would like greater sharing of information by the medical team. They insisted
their child always be "placed first" and that the team be transparent with their
use of technology. Computer technology may create possible obstructions and
distractions to the medical team. As computer technologies become more
commonplace in medicine, maintaining the essence of good patient-communication
and family centered care is essential.
PMID- 29348274
TI - Sinogenic intracranial complications: is adalimumab a culprit?
AB - We present two 11-year-old girls with chronic recurrent multifocal osteomyelitis,
treated with adalimumab. Both developed severe intracranial complications to
sinusitis. Patient 1 had been treated with adalimumab for 15 months when she
developed acute sinusitis complicated by an orbital abscess, forehead swelling, a
subdural empyema and osteomyelitis of the frontal bone. She was treated with a
rhinosurgical and neurosurgical approach with intravenous antibiotics.Patient 2
had been in adalimumab treatment for 10 weeks. Adalimumab was discontinued 8
weeks prior to developing subdural empyema and subcortical abscesses in
combination with sinusitis. She was treated with endoscopic sinus surgery and
intravenous antibiotics. Both patients had developed psoriasis and episodes of
infection during treatment. They were non-septic and had low fever on
presentation. None of the patients suffered any long-term neurological sequelae.
The immunosuppressive treatment with adalimumab is considered to be the cause of
the sinogenic intracranial complications in our cases.
PMID- 29348275
TI - Microangiopathies in pregnancy.
AB - Thrombotic thrombocytopenic purpura (TTP) is a potentially reversible, life
threatening medical emergency. We present a case of a 21-year-old female with
evidence of haemolytic anaemia based on the presence of positive markers of
haemolysis. Negative Coomb's test, thrombocytopenia and placental infarcts raised
suspicion for a thrombotic microangiopathy. She was diagnosed with TTP and
managed with emergency plasma exchange. Her recovery was immediate.A presumptive
diagnosis of TTP should be based on the presence of microangiopathic haemolytic
anaemia with thrombocytopenia and plasma exchange should be initiated while
complete work up is pending. Using the regular pentad solely for diagnosis of TTP
will lead to underdiagnosis of many cases and should be avoided.Several
microangiopathies can be seen during pregnancy including TTP/atypical haemolytic
uraemic syndrome, HELLP syndrome, pre-eclampsia, disseminated intravascular
coagulopathy and antiphospholipid antibody syndrome. Distinction between each
type will be the focus of our discussion as treatment decisions differ
accordingly.
PMID- 29348276
TI - Congenital tuberculosis presenting as otorrhoea in a preterm infant.
AB - A premature infant of 25 weeks' gestational age presented at 8 weeks after birth
with otorrhoea from the left ear. Following a course of topical and systemic
antibiotics, the patient deteriorated developing facial nerve paralysis and
cervical lymphadenitis. Contrast-enhanced CT and MRI of the head showed a
destructive process of the left temporal bone. These findings prompted the
clinicians to send swabs from the purulent discharge from the ear for acid-fast
bacilli stain. Furthermore, surgical exploration and debridement were undertaken.
Cultures from ear discharge and biopsy-taken during surgical procedure-revealed
the presence of Mycobacterium tuberculosis complex. The patient developed
necrotizing otitis media, left temporal bone osteomyelitis and cervical
lymphadenitis. The infant's mother was found to have an endometrial biopsy
positive for M. tuberculosis suggesting the diagnosis of congenital tuberculosis.
PMID- 29348277
TI - Chronic strongyloidiasis with recurrent asthma exacerbations and steroid
associated 'hives'.
AB - A 74-year-old man experienced worsening asthma for several years. Oral steroids
were required on multiple occasions for asthma treatment. During his steroid
courses, he developed a hive-like rash, which would resolve after completion of
each steroid course. He was from Romania, and had lived in the USA for many
years. Laboratory testing had shown eosinophilia. He was eventually diagnosed
with strongyloidiasis by serology. Treatment with ivermectin led to marked
improvement but not resolution of his long-term asthma. His hive-like rash, which
was likely larva currens, did not recur with a subsequent steroid course.
Improved recognition of strongyloidiasis, particularly in steroid-treated
patients, is needed.
PMID- 29348279
TI - 'Clinically suspected myocarditis with pseudoinfarct presentation' complicated
with left ventricular aneurysm.
AB - A 51-year-old man presented with chest pain, high troponin level, inflammatory
syndrome and ST-segment elevation in the anterior leads. While the transthoracic
echocardiogram (TTE) showed anteroseptal hypokinesis and apical akinesis, the
coronary angiogram was normal. Cardiac MR demonstrated a typical aspect of
myocarditis (multiple areas of mid-myocardial late gadolinium enhancement,
sparing the subendocardial layer, along with oedema). The initial diagnosis was
clinically suspected myocarditis with pseudoinfarct presentation. However, the
short-term evolution was not typical of this syndrome, since an apical transmural
scar with aneurysm developed within 2 weeks. Seven years later, the patient
remained asymptomatic, while Q waves persisted in anterior leads along with an
apical aneurysm on TTE. A transmural myocardial necrosis with aneurysm is an
unusual complication of acute myocarditis. The potential mechanisms accounting
for the development of these lesions are reviewed, and the clinical implications
for the diagnosis and monitoring of acute myocarditis are discussed.
PMID- 29348278
TI - A ping-pong ball in left atrium.
PMID- 29348280
TI - Marked cachexia in probable invasive pulmonary aspergillosis with bronchopleural
fistula.
AB - A 49-year-old man with a medical history of diabetes and heavy smoking was
admitted to intensive care with severe bilateral pneumonia associated with marked
cachexia. He developed a complex right-sided bronchopleural fistula and was
transferred to our tertiary centre for consideration of surgical
intervention.Despite escalation of antibiotic therapy, he did not improve and
further investigations led to a diagnosis of invasive pulmonary aspergillosis.
Definitive treatment plans required a right pneumonectomy; however, given the
severity of cachexia, he remained unable to undergo such a large operation. This
case demonstrates an atypical presentation of invasive pulmonary aspergillosis in
a mildly immunodeficient individual. It highlights the challenges in assessment
and management of critically ill patients' nutrition as well as optimal timing
for surgical intervention.
PMID- 29348281
TI - Early intrauterine pregnancy during major surgery: the importance of preoperative
assessment and advice.
AB - We present a case of a live birth occurring post radical laparoscopic excision of
endometriosis, hysteroscopy, curettage and test of tubal patency in the presence
of an early intrauterine gestation.
PMID- 29348282
TI - Acquired pyloric stenosis resulting in hypokalaemic, hyperchloraemic normal anion
gap metabolic acidosis. Persistent vomiting in an adult: cause and effect.
AB - A 24-year-old woman presented with a history of persistent vomiting for at least
3 months. This resulted in severe dehydration with risk of acute kidney injury.
In addition to volume depletion, loss of gastric fluid resulted in a specific
metabolic derangement-hypokalaemic, hypochloraemic normal anion gap metabolic
alkalosis with a reduced ionised calcium concentration and paradoxical aciduria.
These metabolic changes were reflected in her ECG. Investigation demonstrated
acquired gastric outflow tract obstruction secondary to a pyloric peptic ulcer.
The patient was resuscitated with intravenous crystalloid and electrolyte
supplements. The acquired pyloric stenosis was treated medically with a proton
pump inhibitor and Helicobacter pylori eradication therapy with excellent
recovery.
PMID- 29348283
TI - Unusual 'feathery' cause of a parapharyngeal abscess in an infant.
AB - A 7-month-old boy presented to the emergency department with reduced oral intake,
neck swelling and fever. Clinical examination revealed a 3 cm left parotid and
left level I neck swelling with left medialised tonsil but no trismus. Computed
imaging confirmed the presence of an abscess in the peritonsillar area with
extension into the parapharyngeal space and deep lobe of the parotid gland. The
abscess was incised and drained transorally. Following drainage of the abscess, a
small 3 mm suspicious foreign body was seen. After extraction, this was revealed
to be a 60 mm feather. We would like to highlight this unusual case in an infant
and to ensure that foreign body is considered as aetiology. There are only a
handful of cases in the literature involving feathers causing neck abscesses and,
to our knowledge, this is the first case where the patient presented with a
pharyngeal abscess, which was drained transorally.
PMID- 29348284
TI - Laryngeal tuberculosis: a rare cause of critical airway obstruction.
AB - Laryngeal tuberculosis (TB) is a rare condition, occurring in less than 1% of
patients infected with pulmonary TB. We present a case of a 57-year-old male
patient, who presented in extremis with audible stridor, increased work of
breathing and cyanosis. In addition, the patient had a complex medical history,
including a recent diagnosis of congenital malformation of the epiglottis.
Emergency intervention was required to secure the airway, and after initial
attempts at intubation were unsuccessful, an emergency tracheostomy was
performed. Four days after initial presentation, his sputum tested positive for
acid-fast bacilli, and a subsequent CT chest revealed pulmonary as well as
laryngeal TB, which was confirmed on biopsy of the larynx. The patient was
commenced on a 24-week course of anti-tuberculous treatment and was successfully
decannulated 6 months after the emergency airway was established.
PMID- 29348285
TI - Vancomycin-induced coronary artery spasm: a case of Kounis syndrome.
AB - Kounis syndrome defined as the appearance of acute coronary syndrome in the
context of an allergic reaction is a relatively rare phenomenon. There are three
variants of this syndrome in which the patient presents with symptoms of an acute
chest. Herein, we describe a case of an 83-year-old woman who demonstrated type I
variant of Kounis syndrome in response to vancomycin administration. After
initialisation of vancomycin, she became unresponsive and an ECG demonstrated ST
changes consistent with inferior-lateral myocardial infarction. Once allergic
stimulus was removed, ECG normalised. Differential diagnosis includes, myocardial
infarctions, angina as well as intravascular stent thrombosis, which must all be
ruled out. The patient was monitored and discharged soon thereafter.
PMID- 29348286
TI - Portal vein embolisation in a patient with situs inversus.
AB - Portal vein embolisation (PVE) is a well-established technique used for patients
who require major hepatic resections without sufficient volume of future remnant
liver (FRL). We describe a case of PVE in a patient with situs inversus. Computed
Tomography (CT) 4 weeks after the procedure demonstrated significant hypertrophy
of the FRL. However, the surgical procedure was aborted due to signs of
extrahepatic progression.
PMID- 29348287
TI - Recurrent hiccups may signal brainstem pathology and should be investigated.
AB - While occasional hiccups are normal, their persistent recurrence is distressing
and may have an underlying aetiology. Patients with recurrent hiccups may undergo
a long journey and see many physicians before the diagnosis is finally made. The
purpose of this report is to increase awareness of central nervous system lesions
as a possible cause for recurrent hiccups and provide an illustrative case of an
otherwise fit man presenting with ongoing hiccups caused by a medullary
haemangioblastoma.
PMID- 29348288
TI - Budd-Chiari syndrome: a rare and life-threatening complication of Crohn's
disease.
AB - Budd-Chiari syndrome (BCS) is characterised by obstruction of hepatic venous
outflow and may be triggered by the prothrombotic state associated with
inflammatory bowel disease (IBD). We reported a case of Crohn's disease (CD) that
presented with anasarca, ascites, symptomatic hepatomegaly, elevated liver
enzymes, increased prothrombin time and low albumin. Oesophagogastroduodenoscopy
and colonoscopy confirmed active CD. Abdominal CT showed hepatic vein thrombosis.
Liver biopsy revealed severe perivenular sinusoidal dilation with areas of
hepatocyte dropout, bands of hepatocyte atrophy and centrizonal fibrosis,
suggestive of BCS. The patient was treated with steroids for CD and systemic
anticoagulants for BCS. His liver function and enzymes normalised, and he
reported symptomatic improvement. The precise mechanism responsible for increased
hypercoagulability in IBD remains unclear. Early recognition and treatment for
possible thrombotic complications of CD is critical to prevent potentially fatal
events like pulmonary embolism or liver failure.
PMID- 29348289
TI - Urinary Bladder Mass Due To Chronic Lymphocytic Leukaemia.
PMID- 29348290
TI - An unusual case of basilar artery aneurysm presenting with spastic quadriparesis.
AB - Unruptured aneurysm usually presents with headache and neuro-ophthalmic features;
when it ruptures, it presents with subarachnoid haemorrhage. Basilar artery
aneurysm represents only 3-5% of cerebral aneurysms. Non-haemorrhagic symptoms
and the signs of unruptured aneurysms are manifested as mass effect,
thromboembolic phenomenon or epileptical attacks. Clinical presentation of
unruptured aneurysm depends on structures which are involved. In our case, the
patient had insidious onset headache and spastic quadriparesis with sixth cranial
nerve palsy, which implicate involvement of corticospinal pathways at the level
of pons.
PMID- 29348291
TI - Bruns nystagmus: an important clinical clue for cerebellopontine angle tumours.
PMID- 29348292
TI - Morbid jealousy reactivated by mood episodes.
AB - A middle-aged man who has been enduring financial constraint experienced a period
of irritability, increased goal-directed activities and insomnia occurring along
with extreme jealousy with his current wife. The episode was followed by
depressed mood and non-prominent auditory hallucination. His previous history
revealed a forensic psychiatry case of a murder he committed 20 years ago.
PMID- 29348293
TI - Defining limited stage small cell lung cancer: a radiation oncologist's
perspective.
PMID- 29348294
TI - Sarcomatoid carcinoma of the duodenum.
PMID- 29348296
TI - CART Targeting of Solid Tumors: More Pieces to the Puzzle.
AB - Chimeric antigen receptor-modified T (CART)-cell-based targeting of solid tumors
remains a considerable and worthwhile challenge in the field of immunotherapy.
The role of chemotherapy to target stroma and enhance chimeric antigen receptor
(CAR) cell antitumor function, expansion, and persistence is still unresolved.
Clin Cancer Res; 24(6); 1246-7. (c)2018 AACRSee related article by Guo et al., p.
1277.
PMID- 29348295
TI - Tuning CRISPR-Cas9 Gene Drives in Saccharomyces cerevisiae.
AB - Control of biological populations is an ongoing challenge in many fields,
including agriculture, biodiversity, ecological preservation, pest control, and
the spread of disease. In some cases, such as insects that harbor human pathogens
(e.g., malaria), elimination or reduction of a small number of species would have
a dramatic impact across the globe. Given the recent discovery and development of
the CRISPR-Cas9 gene editing technology, a unique arrangement of this system, a
nuclease-based "gene drive," allows for the super-Mendelian spread and forced
propagation of a genetic element through a population. Recent studies have
demonstrated the ability of a gene drive to rapidly spread within and nearly
eliminate insect populations in a laboratory setting. While there are still
ongoing technical challenges to design of a more optimal gene drive to be used in
wild populations, there are still serious ecological and ethical concerns
surrounding the nature of this powerful biological agent. Here, we use budding
yeast as a safe and fully contained model system to explore mechanisms that might
allow for programmed regulation of gene drive activity. We describe four
conserved features of all CRISPR-based drives and demonstrate the ability of each
drive component-Cas9 protein level, sgRNA identity, Cas9 nucleocytoplasmic
shuttling, and novel Cas9-Cas9 tandem fusions-to modulate drive activity within a
population.
PMID- 29348297
TI - Changes in macrophage transcriptome associate with systemic sclerosis and mediate
GSDMA contribution to disease risk.
AB - OBJECTIVES: Several common and rare risk variants have been reported for systemic
sclerosis (SSc), but the effector cell(s) mediating the function of these genetic
variants remains to be elucidated. While innate immune cells have been proposed
as the critical targets to interfere with the disease process underlying SSc, no
studies have comprehensively established their effector role. Here we
investigated the contribution of monocyte-derived macrophages (MDMs) in mediating
genetic susceptibility to SSc. METHODS: We carried out RNA sequencing and genome
wide genotyping in MDMs from 57 patients with SSc and 15 controls. Our
differential expression and expression quantitative trait locus (eQTL) analysis
in SSc was further integrated with epigenetic, expression and eQTL data from
skin, monocytes, neutrophils and lymphocytes. RESULTS: We identified 602 genes
upregulated and downregulated in SSc macrophages that were significantly enriched
for genes previously implicated in SSc susceptibility (P=5*10-4), and 270 cis
regulated genes in MDMs. Among these, GSDMA was reported to carry an SSc risk
variant (rs3894194) regulating expression of neighbouring genes in blood. We show
that GSDMA is upregulated in SSc MDMs (P=8.4*10-4) but not in the skin, and is a
significant eQTL in SSc macrophages and lipopolysaccharide/interferon gamma
(IFNgamma)-stimulated monocytes. Furthermore, we identify an SSc macrophage
transcriptome signature characterised by upregulation of glycolysis, hypoxia and
mTOR signalling and a downregulation of IFNgamma response pathways. CONCLUSIONS:
Our data further establish the link between macrophages and SSc, and suggest that
the contribution of the rs3894194 risk variant to SSc susceptibility can be
mediated by GSDMA expression in macrophages.
PMID- 29348299
TI - Seven days in medicine: 10-16 January 2018.
PMID- 29348300
TI - Letter to the GMC chair regarding Hadiza Bawa-Garba.
PMID- 29348298
TI - A Review of Prostate Cancer Genome-Wide Association Studies (GWAS).
AB - Prostate cancer is the most common cancer in men in Europe and the United States.
The genetic heritability of prostate cancer is contributed to by both rarely
occurring genetic variants with higher penetrance and moderate to commonly
occurring variants conferring lower risks. The number of identified variants
belonging to the latter category has increased dramatically in the last 10 years
with the development of the genome-wide association study (GWAS) and the
collaboration of international consortia that have led to the sharing of large
scale genotyping data. Over 40 prostate cancer GWAS have been reported, with
approximately 170 common variants now identified. Clinical utility of these
variants could include strategies for population-based risk stratification to
target prostate cancer screening to men with an increased genetic risk of disease
development, while for those who develop prostate cancer, identifying genetic
variants could allow treatment to be tailored based on a genetic profile in the
early disease setting. Functional studies of identified variants are needed to
fully understand underlying mechanisms of disease and identify novel targets for
treatment. This review will outline the GWAS carried out in prostate cancer and
the common variants identified so far, and how these may be utilized clinically
in the screening for and management of prostate cancer. Cancer Epidemiol
Biomarkers Prev; 27(8); 845-57. (c)2018 AACR.
PMID- 29348301
TI - Predicting the presence of macrovascular causes in non-traumatic intracerebral
haemorrhage: the DIAGRAM prediction score.
AB - OBJECTIVE: A substantial part of non-traumatic intracerebral haemorrhages (ICH)
arises from a macrovascular cause, but there is little guidance on selection of
patients for additional diagnostic work-up. We aimed to develop and externally
validate a model for predicting the probability of a macrovascular cause in
patients with non-traumatic ICH. METHODS: The DIagnostic AngioGRAphy to find
vascular Malformations (DIAGRAM) study (n=298; 69 macrovascular cause; 23%) is a
prospective, multicentre study assessing yield and accuracy of CT angiography
(CTA), MRI/ magnetic resonance angiography (MRA) and intra-arterial catheter
angiography in diagnosing macrovascular causes in patients with non-traumatic
ICH. We considered prespecified patient and ICH characteristics in multivariable
logistic regression analyses as predictors for a macrovascular cause. We combined
independent predictors in a model, which we validated in an external cohort of
173 patients with ICH (78 macrovascular cause, 45%). RESULTS: Independent
predictors were younger age, lobar or posterior fossa (vs deep) location of ICH,
and absence of small vessel disease (SVD). A model that combined these predictors
showed good performance in the development data (c-statistic 0.83; 95% CI 0.78 to
0.88) and moderate performance in external validation (c-statistic 0.66; 95% CI
0.58 to 0.74). When CTA results were added, the c-statistic was excellent (0.91;
95% CI 0.88 to 0.94) and good after external validation (0.88; 95% CI 0.83 to
0.94). Predicted probabilities varied from 1% in patients aged 51-70 years with
deep ICH and SVD, to more than 50% in patients aged 18-50 years with lobar or
posterior fossa ICH without SVD. CONCLUSION: The DIAGRAM scores help to predict
the probability of a macrovascular cause in patients with non-traumatic ICH based
on age, ICH location, SVD and CTA.
PMID- 29348303
TI - Absence epilepsy beyond adolescence: an outcome analysis after 45 years of follow
up.
AB - OBJECTIVES: Depending on patient age at onset, absence epilepsy is subdivided
into childhood and juvenile forms. Absence seizures can occur several times per
day (pyknoleptic course) or less frequently than daily (non-pyknoleptic course).
Seizures typically terminate before adulthood, but a quarter of patients need
ongoing treatment beyond adolescence. Little is known about their long-term
seizure and psychosocial outcome. METHODS: Files of 135 outpatients with absence
epilepsy (76 females; 123 had additional generalised tonic-clonic seizures) were
retrospectively analysed after a median follow-up of 45.4 years (IQR: 31.9-56.2).
Eighty-two subjects completed an additional interview. Patients were dichotomised
according to age at epilepsy onset (childhood: n=82; juvenile: n=53) and course
of absence seizures (pyknoleptic: n=80; non-pyknoleptic: n=55). RESULTS: Among
all patients, 53% achieved 5-year terminal seizure remission, 16% without
antiepileptic medication. Median age at last seizure was lower in patients with
childhood onset of absence epilepsy (37.7 years) versus juvenile onset (44.4
years; P<=0.01). However, rates and duration of terminal seizure remission were
similar. Pyknoleptic versus non-pyknoleptic course of absence seizures made no
difference for long-term seizure outcome. Multivariate analysis identified only
higher age at investigation to be associated with terminal 5-year seizure
remission. Regarding aspects of psychosocial outcome, there were no significant
differences between the respective subgroups. CONCLUSIONS: These data indicate
that if absence epilepsy persists beyond adolescence, long-term seizure and
psychosocial outcome do not differ between childhood and juvenile onset or
between pyknoleptic and non-pyknoleptic course of absence epilepsy. However,
higher patient age increases the chance of terminal seizure remission.
PMID- 29348302
TI - Tracking brain damage in progressive supranuclear palsy: a longitudinal MRI
study.
AB - OBJECTIVES: In this prospective, longitudinal, multiparametric MRI study, we
investigated clinical as well as brain grey matter and white matter (WM) regional
changes in patients with progressive supranuclear palsy-Richardson's syndrome
(PSP-RS). METHODS: Twenty-one patients with PSP-RS were evaluated at baseline
relative to 36 healthy controls and after a mean follow-up of 1.4 years with
clinical rating scales, neuropsychological tests and MRI scans. RESULTS: Relative
to controls, patients with PSP-RS showed at baseline a typical pattern of brain
damage, including midbrain atrophy, frontal cortical thinning and widespread WM
involvement of the main infratentorial and supratentorial tracts that exceeded
cortical damage. Longitudinal study showed that PSP-RS exhibited no further
changes in cortical thinning, which remained relatively focal, while midbrain
atrophy and WM damage significantly progressed. Corpus callosum and frontal WM
tract changes correlated with the progression of both disease severity and
behavioural dysfunction. CONCLUSIONS: This study demonstrated the feasibility of
carrying out longitudinal diffusion tensor MRI in patients with PSP-RS and its
sensitivity to identifying the progression of pathology. Longitudinal midbrain
volume loss and WM changes are associated with PSP disease course.
PMID- 29348304
TI - miR-20a-5p promotes adipogenic differentiation of murine bone marrow stromal
cells via targeting Kruppel-like factor 3.
AB - miR-20a-5p has recently been identified to induce adipogenesis of established
adipogenic cell lines in our previous study. However, its role and molecular
mechanisms in the regulation of adipocyte lineage commitment of bone marrow
derived stromal cells (BMSCs) still need to be explored. In this report, we
demonstrated the expression of miR-20a-5p was promoted gradually during
adipogenic differentiation in BMSCs. We also confirmed that miR-20a-5p has a
positive function in the adipogenic differentiation of BMSCs by gain-of-function
study with overexpression lentivirus or synthetic mimics of miR-20a-5p, and loss
of-function study with sponge lentivirus or synthetic inhibitor of miR-20a-5p.
Dual luciferase reporter assay, GFP repression assay and Western blotting
suggested Kruppel-like factor 3 (Klf3) was a direct target of miR-20a-5p.
Furthermore, siRNA-mediated silencing of Klf3 recapitulated the potentiation of
adipogenesis induced by miR-20a-5p overexpression, whereas enhanced expression of
Klf3 attenuated the effect of miR-20a-5p. As Klf3 was reported to play an
inhibitory role in adipogenesis at the initial stage of differentiation, the
findings we present here indicate that miR-20a-5p promotes adipocyte
differentiation from BMSCs by targeting and negatively regulating Klf3 in the
early phase during the procedure of adipogenesis.
PMID- 29348305
TI - The evolving clinical, genetic and therapeutic landscape of multiple endocrine
neoplasia type 2.
PMID- 29348306
TI - Novel targeted therapeutics for MEN2.
AB - The rearranged during transfection (RET) proto-oncogene was recognized as the
multiple endocrine neoplasia type 2 (MEN2) causing gene in 1993. Since then, much
effort has been put into a clear understanding of its oncogenic signaling, its
biochemical function and ways to block its aberrant activation in MEN2 and
related cancers. Several small molecules have been designed, developed or
redirected as RET inhibitors for the treatment of MEN2 and sporadic MTC. However,
current drugs are mostly active against several other kinases, as they were not
originally developed for RET. This limits efficacy and poses safety issues.
Therefore, there is still much to do to improve targeted MEN2 treatments. New,
more potent and selective molecules, or combinatorial strategies may lead to more
effective therapies in the near future. Here, we review the rationale for RET
targeting in MEN2, the use of currently available drugs and novel preclinical and
clinical RET inhibitor candidates.
PMID- 29348308
TI - Refining genetic stratification in T-ALL.
PMID- 29348309
TI - Editing gene engineering to enhance function.
PMID- 29348307
TI - Non-mammalian models of multiple endocrine neoplasia type 2.
AB - Twenty-five years ago, RET was identified as the primary driver of multiple
endocrine neoplasia type 2 (MEN2) syndrome. MEN2 is characterized by several
transformation events including pheochromocytoma, parathyroid adenoma and,
especially penetrant, medullary thyroid carcinoma (MTC). Overall, MTC is a rare
but aggressive type of thyroid cancer for which no effective treatment currently
exists. Surgery, radiation, radioisotope treatment and chemotherapeutics have all
shown limited success, and none of these approaches have proven durable in
advanced disease. Non-mammalian models that incorporate the oncogenic RET
isoforms associated with MEN2 and other RET-associated diseases have been useful
in delineating mechanisms underlying disease progression. These models have also
identified novel targeted therapies as single agents and as combinations. These
studies highlight the importance of modeling disease in the context of the whole
animal, accounting for the complex interplay between tumor and normal cells in
controlling disease progression as well as response to therapy. With convenient
access to whole genome sequencing data from expanded thyroid cancer patient
cohorts, non-mammalian models will become more complex, sophisticated and
continue to complement future mammalian studies. In this review, we explore the
contributions of non-mammalian models to our understanding of thyroid cancer
including MTC, with a focus on Danio rerio and Drosophila melanogaster (fish and
fly) models.
PMID- 29348310
TI - ASXL1 mutations gain a function.
PMID- 29348311
TI - Prochemerin processing by factor XIa.
PMID- 29348312
TI - Composite morphologically and immunohistochemically distinct classical and
pleomorphic mantle cell lymphomas.
PMID- 29348313
TI - Sood R, Kamikubo Y, Liu P. Role of RUNX1 in hematological malignancies. Blood.
2017;129(15):2070-2082.
PMID- 29348315
TI - Whole-Body Biodistribution and Dosimetry of the Dopamine Transporter Radioligand
18F-FE-PE2I in Human Subjects.
AB - 18F-(E)-N-(3-iodoprop-2-enyl)-2beta-carbofluoroethoxy-3beta-(4'-methyl-phenyl)
nortropane (18F-FE-PE2I) was recently developed and has shown adequate affinity
and high selectivity for the dopamine transporter (DAT). Previous studies have
shown promising results for 18F-FE-PE2I as a suitable radioligand for DAT
imaging. In this study, we investigated the whole-body biodistribution and
dosimetry of 18F-FE-PE2I in healthy volunteers to support its utility as a
suitable PET imaging agent for the DAT. Methods: Five healthy volunteers were
given a mean activity of 2.5 MBq/kg, and 3 PET scans, head to thigh, were
performed immediately after injection followed by 4 whole-body PET/CT scans
between 0.5 and 6 h after injection. Blood samples were drawn in connection with
the whole-body scans, and all urine was collected until 6 h after injection.
Volumes of interest were delineated around 17 organs on all images, and the areas
under the time-activity curves were calculated to obtain the total number of
decays in the organs. The absorbed doses to organs and the effective dose were
calculated using the software IDAC. Results: The highest activity concentration
was observed in the liver (0.9%-1.2% injected activity/100 g) up to 30 min after
injection. At later time points, the highest concentration was seen in the
gallbladder (1.1%-0.1% injected activity/100 g). The activity excreted with urine
ranged between 23% and 34%, with a mean of 28%. The urinary bladder received the
highest absorbed dose (119 MUGy/MBq), followed by the liver (46 MUGy/MBq). The
effective dose was 23 MUSv/MBq (range, 19-28 MUSv/MBq), resulting in an effective
dose of 4.6 mSv for an administered activity of 200 MBq. Conclusion: The
effective dose is within the same order of magnitude as other commonly used PET
imaging agents as well as DAT agents. The reasonable effective dose, together
with the previously reported favorable characteristics for DAT imaging and
quantification, indicates that 18F-FE-PE2I is a suitable radioligand for DAT
imaging.
PMID- 29348316
TI - Evaluation of Next-Generation Anti-CD20 Antibodies Labeled with 89Zr in Human
Lymphoma Xenografts.
AB - Radioimmunotherapies with monoclonal antibodies to the B-lymphocyte antigen 20
(CD20) are effective treatments for B-cell lymphomas, but U.S. Food and Drug
Administration-approved radioimmunotherapies exclusively use radiolabeled murine
antibodies, potentially limiting redosing. The Food and Drug Administration
recently approved 2 unlabeled anti-CD20 monoclonal antibodies, obinutuzumab and
ofatumumab, termed next generation as they are humanized (obinutuzumab) or fully
human (ofatumumab), thus potentially allowing a greater potential for redosing
than with previous-generation anti-CD20 antibodies, including rituximab
(chimeric) and tositumomab (murine), which contain more murine peptide sequences.
We prepared 89Zr-ofatumumab and 89Zr-obinituzumab and assessed their tumor
targeting by PET/CT imaging and their biodistribution in a preclinical mouse
model with CD20 xenografts to determine whether these antibodies have potential
as theranostics or for radioimmunotherapy. Methods: Obinutuzumab, ofatumumab,
rituximab, tositumomab, and human IgG (as control) were radiolabeled with 89Zr.
Raji Burkitt lymphoma xenografts were established in severe combined
immunodeficient mice. Mice with palpable tumors (n = 4-9) were injected with 89Zr
obinutuzumab, 89Zr-ofatumumab, 89Zr-rituximab, 89Zr-tositumomab, or 89Zr-IgG,
with small-animal PET/CT images acquired at 1, 3, and 7 d after injection, and
then sacrificed for biodistribution analyses. Results: At 1, 3, and 7 d after
injection, all anti-CD20 antibodies showed clear tumor uptake on PET/CT, with
minimal tumor uptake of IgG. Biodistribution data showed significantly (P <
0.005) higher tumor uptake for obinutuzumab (41.4 +/- 7.6 percentage injected
dose [%ID]/g), ofatumumab (32.6 +/- 17.5 %ID/g), rituximab (28.6 +/- 7.6 %ID/g),
and tositumomab (28.0 +/- 6.5 %ID/g) than IgG (7.2 +/- 1.2 %ID/g). Tositumomab
had much higher splenic uptake (186.4 +/- 49.7 %ID/g, P < 0.001) than the other
antibodies. Conclusion:89Zr-labeled obinutuzumab and ofatumumab localized to
tumor as well as or better than labeled rituximab and tositumomab, 2 monoclonal
antibodies that have been used previously in B-cell lymphoma radioimmunotherapy,
and both obinutuzumab and ofatumumab have the potential for repeated dosing.
PMID- 29348317
TI - Head-to-Head Comparison of 11C-PBR28 and 18F-GE180 for Quantification of the
Translocator Protein in the Human Brain.
AB - 18F-GE180 is a third-generation PET tracer for quantifying the translocator
protein (TSPO), a biomarker for inflammation. The aim of this study was to
perform a head-to-head comparison of 18F-GE180 and the well-established TSPO
tracer 11C-PBR28 by scanning with both tracers during the same day in the same
subjects. Methods: Five subjects underwent a 90-min PET scan with 11C-PBR28 in
the morning and 18F-GE180 in the afternoon. A metabolite-corrected arterial input
function was obtained in each subject for both tracers, and the brain uptake was
quantified with a 2-tissue-compartment model. Results: The rate of metabolism of
18F-GE180 in arterial blood was slower than that of 11C-PBR28 (the percentages of
nonmetabolized parent in plasma at 90 min were 74.9% +/- 4.15% [mean +/- SD] and
11.2% +/- 1.90%, respectively). The plasma free fractions were similar for both
tracers: 3.5% +/- 1.1% for 18F-GE180 and 4.1% +/- 1.1% for 11C-PBR28. The average
total volume of distribution (VT) of 18F-GE180 was about 20 times smaller than
that of 11C-PBR28 (0.15 +/- 0.03 mL/cm3 for 18F-GE180 and 3.27 +/- 0.66 mL/cm3
for 11C-PBR28). 18F-GE180 was characterized by poor transfer from the vascular
compartment to the brain (its plasma-to-tissue rate constant [K1] was about 10
times smaller than that of 11C-PBR28). Moreover, kinetic modeling was more
difficult with 18F-GE180, as its VT values were identified with a lower precision
than those of 11C-PBR28 and outlying values were more frequent. Conclusion: The
VT of 18F-GE180 was about 20 times smaller than that of 11C-PBR28 because of low
penetration into the brain from the vascular compartment. In addition, kinetic
modeling of 18F-GE180 was more challenging than that of 11C-PBR28. Therefore,
compared with 11C-PBR28, 18F-GE180 had unfavorable characteristics for TSPO
imaging of the brain.
PMID- 29348318
TI - Reply: Optimizing Strategies for Immune Checkpoint Imaging with Immuno-PET in
Preclinical Study.
PMID- 29348319
TI - Reply: Doxorubicin Effect on Myocardial Metabolism as a Prerequisite for
Subsequent Development of Cardiac Toxicity: Are There Unsuspected Confounders?
PMID- 29348320
TI - 18F-FDG PET/CT in Local Ablative Therapies: A Systematic Review.
AB - Driven by the continuous improvement in the accuracy of cross-sectional imaging,
image-guided minimally invasive local ablative therapies have received
incremental interest over the past few years. In this article, we systematically
review the currently available literature on 18F-FDG PET/CT to monitor the
efficacy of these local ablative therapies. By including all local ablative
treatment modalities, tumor types, and organ sites, we provide a comprehensive
overview of the current status, identify general patterns across studies, and
provide recommendations for future studies and clinical practice. The Quality
Assessment of Diagnostic Accuracy Studies (QUADAS) criteria were used to assess
the quality of the reported diagnostic accuracy of the retrieved studies. Data in
the literature suggest that 18F-FDG PET/CT is a highly accurate tool to assess
the technical success of local treatment, to identify residual or recurrent tumor
early after intervention, and to provide prognostic and predictive information.
However, prospective interventional studies based on 18F-FDG PET/CT findings of
disease activity are mandatory to develop uniform and quantitative criteria for
PET evaluation. Moreover, the optimal timing of 18F-FDG PET/CT after treatment
may vary according to the location of the disease, with very early imaging being
possible in solid organs such as the liver but posttreatment imaging being
challenging for 3 mo in a location such as the lung parenchyma.
PMID- 29348321
TI - Lower Limbic Metabotropic Glutamate Receptor 5 Availability in Alcohol
Dependence.
AB - Animal studies suggest an important role for the metabotropic glutamate receptor
subtype 5 (mGlu5) in the pathophysiology of alcohol dependence, but direct human
evidence is lacking. The goal of this study was to investigate cerebral mGlu5
availability in alcohol-dependent subjects versus controls using 18F-3-fluoro-5
[(pyridin-3-yl)ethynyl]benzonitrile (18F-FPEB) PET. Methods: Dynamic 90-min 18F
FPEB scans combined with arterial blood sampling were acquired for 16 recently
abstinent alcohol-dependent subjects and 32 age-matched controls. Regional mGlu5
availability was quantified by the 18F-FPEB total distribution volume using both
a voxel-by-voxel and a volume-of-interest analysis with partial-volume effect
correction. Alcohol consumption within the last 3 mo was assessed by
questionnaires and by hair ethyl glucuronide analysis. Craving was assessed using
the Desire for Alcohol Questionnaire. Results: mGlu5 availability was lower in
mainly limbic regions of alcohol-dependent subjects than in controls (P < 0.05,
familywise error-corrected), ranging from 14% in the posterior cingulate cortex
to 36% in the caudate nucleus. Lower mGlu5 availability was associated with
higher hair ethyl glucuronide levels for most regions and was related to a lower
level of craving specifically in the middle frontal gyrus, cingulate cortex, and
inferolateral temporal lobe. Conclusion: These findings provide human in vivo
evidence that limbic mGlu5 has a role in the pathophysiology of alcohol
dependence, possibly involved in a compensatory mechanism helping to reduce
craving during abstinence.
PMID- 29348322
TI - Long-Term Risk of Myocardial Infarction Compared to Recurrent Stroke After
Transient Ischemic Attack and Ischemic Stroke: Systematic Review and Meta
Analysis.
AB - BACKGROUND: Uncertainties remain about the current risk of myocardial infarction
(MI) after ischemic stroke or transient ischemic attack. METHODS AND RESULTS: We
undertook a systematic review to estimate the long-term risk of MI, compared to
recurrent stroke, with temporal trends in ischemic stroke/transient ischemic
attack patients. Annual risks and 95% confidence intervals (95% CI) of MI and
recurrent stroke were estimated using random-effect meta-analyses. We calculated
incidence ratios of MI/recurrent stroke, for fatal and nonfatal events, using
similar analyses. Rate ratios for MI in patients with potential risk factors
compared to those without were calculated using Poisson regression.A total of 58
studies (131 299 patients) with a mean (range) follow-up of 3.5 (1.0-10.0) years
were included. The risk of MI was 1.67%/y (95% CI 1.36-1.98, Phet<0.001 for
heterogeneity) and decreased over time (Pint=0.021); 96% of the heterogeneity
between studies was explained by study design, study period, follow-up duration,
mean age, proportion of patients on antithrombotic therapy, and incident versus
combined ischemic stroke/transient ischemic attack. The risk of recurrent stroke
was 4.26%/y (95% CI 3.43-5.09, Phet<0.001), with no change over time (Pint=0.63).
The risk of fatal MI was half the risk of recurrent strokes ending in fatality
(incidence ratio=0.51, 95% CI 0.14-0.89, Phet=0.58). The risk of nonfatal MI was
75% smaller than the risk of recurrent nonfatal stroke (incidence ratio=0.25,
95%CI 0.02-0.50, Phet=0.68). Male sex, hypertension, coronary and peripheral
artery diseases were associated with a doubled risk of MI. CONCLUSIONS: After
ischemic stroke/transient ischemic attack, the risk of MI is currently <2%/y, and
recurrent stroke is a more common cause of death than MI.
PMID- 29348323
TI - Epothilone B Benefits Nigrostriatal Pathway Recovery by Promoting Microtubule
Stabilization After Intracerebral Hemorrhage.
AB - BACKGROUND: Many previous clinical studies have demonstrated that the
nigrostriatal pathway, which plays a vital role in movement adjustment, is
significantly impaired after stroke, according to medical imaging and autopsies.
However, the basic pathomorphological changes have been poorly investigated to
date. This study was designed to explore the pathomorphological changes,
mechanism, and therapeutic method of nigrostriatal impairment after intracerebral
hemorrhage (ICH). METHODS AND RESULTS: Intrastriatal injection of autologous
blood or microtubule depolymerization reagent nocodazole was performed to mimic
the pathology of ICH in C57/BL6 mice. Immunofluorescence, Western blotting,
electron microscopy, functional behavioral tests, and anterograde and retrograde
neural circuit tracking techniques were used in these mice. The data showed that
the number of dopamine neurons and the dopamine concentration were severely
decreased and that fine motor function was impaired after ICH. Microtubule
depolymerization was the main contributor to the loss of dopamine neurons and to
motor function deficits after ICH, as was also proven by intrastriatal injection
of nocodazole. Moreover, administration of the microtubule stabilizer epothilone
B (1.5 mg/kg) improved the integrity of the nigrostriatal pathway neural circuit,
increased the number of dopamine neurons (4598+/-896 versus 3125+/-355; P=0.034)
and the dopamine concentration (4.28+/-0.99 versus 3.08+/-0.75 ng/mg; P=0.041),
and enhanced fine motor functional recovery associated with increased acetylated
alpha-tubulin expression to maintain microtubule stabilization after ICH.
CONCLUSIONS: Our results clarified the pathomorphological changes of the
nigrostriatal pathway after ICH and found that epothilone B helped alleviate
nigrostriatal pathway injury after ICH, associated with promoting alpha-tubulin
acetylation to maintain microtubule stabilization, thus facilitating motor
recovery.
PMID- 29348325
TI - Low-Level, Global Transcription during Mitosis and Dynamic Gene Reactivation
during Mitotic Exit.
AB - Mitosis is thought to be a period of transcriptional silence due to the compact
nature of mitotic chromosomes and the apparent exclusion of RNA Pol II and many
transcription factors from mitotic chromatin. Yet accurate reactivation of a
cell's specific gene expression program is needed to reestablish functional cell
identity after mitosis. The majority of studies on protein regulation and
localization during mitosis have relied extensively on antibodies and cross
linking-based approaches that are known to artifactually exclude proteins from
mitotic chromatin. Here we show that RNA Pol II localization in mitosis is
antibody- and fixation-dependent, and that direct assessment of transcription by
pulse-labeling nascent RNA reveals global, low-level mitotic transcription. We
also find a hierarchy of gene reactivation as the cells transition from mitosis
to their interphase amplitude of gene expression. Resetting of gene transcription
during mitotic exit is coincident with enhancer transcription. Our work thus
shifts focus from assessing mitotic exit as a binary transcription switch to a
more nuanced concert of transcription amplitude and enhancer usage. We suggest
that understanding how gene expression patterns are conserved during mitosis
rests upon deciphering how transcription is maintained by promoters.
PMID- 29348324
TI - PlexinD1 signaling controls morphological changes and migration termination in
newborn neurons.
AB - Newborn neurons maintain a very simple, bipolar shape, while they migrate from
their birthplace toward their destinations in the brain, where they differentiate
into mature neurons with complex dendritic morphologies. Here, we report a
mechanism by which the termination of neuronal migration is maintained in the
postnatal olfactory bulb (OB). During neuronal deceleration in the OB, newborn
neurons transiently extend a protrusion from the proximal part of their leading
process in the resting phase, which we refer to as a filopodium-like lateral
protrusion (FLP). The FLP formation is induced by PlexinD1 downregulation and
local Rac1 activation, which coincide with microtubule reorganization and the
pausing of somal translocation. The somal translocation of resting neurons is
suppressed by microtubule polymerization within the FLP The timing of neuronal
migration termination, controlled by Sema3E-PlexinD1-Rac1 signaling, influences
the final positioning, dendritic patterns, and functions of the neurons in the OB
These results suggest that PlexinD1 signaling controls FLP formation and the
termination of neuronal migration through a precise control of microtubule
dynamics.
PMID- 29348327
TI - Genome Instability as a Consequence of Defects in the Resolution of Recombination
Intermediates.
AB - The efficient processing of homologous recombination (HR) intermediates, which
often contain four-way structures known as Holliday junctions (HJs), is required
for proper chromosome segregation at mitosis. Eukaryotic cells possess three
distinct pathways of resolution: (i) HJ dissolution mediated by BLM-topoisomerase
IIIalpha-RMI1-RMI2 (BTR) complex, and HJ resolution catalyzed by either (ii) SLX1
SLX4-MUS81-EME1-XPF-ERCC1 (SMX complex) or (iii) GEN1. The BTR pathway acts at
all times throughout the cell cycle, whereas the actions of SMX and GEN1 are
restrained in S phase and become elevated late in the cell cycle to ensure the
resolution of persistent recombination intermediates before mitotic division. By
developing a "resolvase-deficient" model system in which the activities of MUS81
and GEN1 are compromised, we have explored the fate of unresolved recombination
intermediates. We find that covalently linked sister chromatids promote the
formation of a new class of ultrafine bridges at anaphase that we term HR-UFBs.
These bridges are broken at cell division, leading to activation of the DNA
damage checkpoint and repair by nonhomologous end joining (NHEJ) in the next cell
cycle. As a consequence, high levels of gross chromosomal rearrangements and
aberrations are observed, together with frequent cell death. These results show
that the HJ resolvases provide essential functions for the resolution of
recombination intermediates, even in cells that remain proficient for BTR
mediated HJ dissolution.
PMID- 29348326
TI - Symmetry from Asymmetry or Asymmetry from Symmetry?
AB - The processes of DNA replication and mitosis allow the genetic information of a
cell to be copied and transferred reliably to its daughter cells. However, if DNA
replication and cell division were always performed in a symmetric manner, the
result would be a cluster of tumor cells instead of a multicellular organism.
Therefore, gaining a complete understanding of any complex living organism
depends on learning how cells become different while faithfully maintaining the
same genetic material. It is well recognized that the distinct epigenetic
information contained in each cell type defines its unique gene expression
program. Nevertheless, how epigenetic information contained in the parental cell
is either maintained or changed in the daughter cells remains largely unknown.
During the asymmetric cell division (ACD) of Drosophila male germline stem cells,
our previous work revealed that preexisting histones are selectively retained in
the renewed stem cell daughter, whereas newly synthesized histones are enriched
in the differentiating daughter cell. We also found that randomized inheritance
of preexisting histones versus newly synthesized histones results in both stem
cell loss and progenitor germ cell tumor phenotypes, suggesting that programmed
histone inheritance is a key epigenetic player for cells to either remember or
reset cell fates. Here, we will discuss these findings in the context of current
knowledge on DNA replication, polarized mitotic machinery, and ACD for both
animal development and tissue homeostasis. We will also speculate on some
potential mechanisms underlying asymmetric histone inheritance, which may be used
in other biological events to achieve the asymmetric cell fates.
PMID- 29348328
TI - Correction for Johnson et al., "Complete Genome Sequences for 35 Biothreat Assay
Relevant Bacillus Species".
PMID- 29348329
TI - Draft Genome Sequences of 510 Listeria monocytogenes Strains from Food Isolates
and Human Listeriosis Cases from Northern Italy.
AB - Listeriosis outbreaks are frequently multistate/multicountry outbreaks,
underlining the importance of molecular typing data for several diverse and well
characterized isolates. Large-scale whole-genome sequencing studies on Listeria
monocytogenes isolates from non-U.S. locations have been limited. Herein, we
describe the draft genome sequences of 510 L. monocytogenes isolates from
northern Italy from different sources.
PMID- 29348330
TI - Complete Genome Sequence of Escherichia coli Bacteriophage PGT2.
AB - Bacteriophage PGT2 was isolated from horse feces by using an uncharacterized
Escherichia coli strain, 7s, isolated from the same sample as the host.
Bacteriophage PGT2 and a related phage, phiKT, which was previously isolated from
the same source, are likely to represent a new genus within the Autographivirinae
subfamily of the Podoviridae family of viruses.
PMID- 29348331
TI - Draft Genome Sequences of Two Vibrio parahaemolyticus Strains Associated with
Gastroenteritis after Raw Seafood Ingestion in Colorado.
AB - Vibrio parahaemolyticus is a Gram-negative pathogen associated with
gastrointestinal and wound infections after exposure to raw seafood or
contaminated waters. We report here the whole-genome sequences of two stool
isolates (CDC-AM50933 and CDC-AM43539) from patients in Colorado presenting with
gastroenteritis after ingesting raw seafood.
PMID- 29348332
TI - Draft Genome Sequence of Mycobacterium setense CSUR47.
AB - Mycobacterium setense CSUR47 is a rapidly growing Mycobacterium species strain
isolated from pus collected from a left maxillary sinus in Marseille, France.
Here, we report the complete 6,278,097-bp genome sequence of M. setense CSUR47,
which exhibits a 66.40% GC content and encodes 5,863 protein-coding genes, 48
tRNAs, and 9 rRNAs.
PMID- 29348333
TI - Draft Genome Sequence and Annotation of the Obligate Bacterial Endosymbiont
Caedibacter taeniospiralis, Causative Agent of the Killer Phenotype in Paramecium
tetraurelia.
AB - Caedibacter taeniospiralis is an obligate endosymbiont living in the cytoplasm of
Paramecium tetraureliaC. taeniospiralis causes the so-called killer trait,
eliminating intraspecific competitors of its host when released into the medium
by the concerted action of the unusual protein structure R-body (refractile body)
in addition to an as-yet-unknown toxin.
PMID- 29348334
TI - Draft Genome Sequences of Phenotypically Distinct Janthinobacterium sp. Isolates
Cultured from the Hudson Valley Watershed.
AB - Investigation of the Hudson Valley watershed reveals many violacein-producing
bacteria. These are of interest for their biotherapeutic potential in treating
chytrid infections of amphibians. The draft whole-genome sequences for seven
Janthinobacterium isolates with a variety of phenotypes are provided in this
study.
PMID- 29348335
TI - Complete Genome Sequence of the African Green Monkey Simian Foamy Virus Serotype
3 Strain FV2014 (SFVcae_FV2014).
AB - The full-length sequence of simian foamy virus serotype 3 (SFV-3) strain FV2014,
an African green monkey (Chlorocebus aethiops) isolate, was obtained using high
throughput sequencing. SFVcae_FV2014 consisted of 13,127 bp and had a genomic
organization similar to those of other SFVs but was distinct from SFV strain LK3,
isolated from the same monkey species.
PMID- 29348336
TI - Nine Whole-Genome Assemblies of Yersinia pestis subsp. microtus bv. Altaica
Strains Isolated from the Altai Mountain Natural Plague Focus (No. 36) in Russia.
AB - We report here the draft genome sequences of nine Yersinia pestis subsp. microtus
bv. Altaica strains isolated from the Altai Mountain plague focus (no. 36), which
represent the 0.PE4 phylogroup circulating in populations of Mongolian pika
(Ochotona pallasi).
PMID- 29348337
TI - Complete Genome Sequence of Sphingorhabdus sp. YGSMI21, Exhibiting High
Enantioselective Epoxide Hydrolase Activity.
AB - Sphingorhabdus sp. YGSMI21 is a novel strain exhibiting high enantioselective
hydrolysis activity for styrene oxide. Here, we present its complete genome
sequence, consisting of one circular chromosome (3.86 Mb) and one plasmid (0.196
Mb).
PMID- 29348338
TI - Draft Genome Sequence of a Novel Bacterium, Pseudomonas sp. Strain MR 02, Capable
of Pyomelanin Production, Isolated from the Mahananda River at Siliguri, West
Bengal, India.
AB - The draft genome sequence of a novel strain, Pseudomonas sp. MR 02, a pyomelanin
producing bacterium isolated from the Mahananda River at Siliguri, West Bengal,
India, is reported here. This strain has a genome size of 5.94 Mb, with an
overall G+C content of 62.6%. The draft genome reports 5,799 genes (mean gene
length, 923 bp), among which 5,503 are protein-coding genes, including the genes
required for the catabolism of tyrosine or phenylalanine for the characteristic
production of homogentisic acid (HGA). Excess HGA, on excretion, auto-oxidizes
and polymerizes to form pyomelanin.
PMID- 29348339
TI - Draft Genome Sequences of Strains TRE 1, TRE D, TRE H, and TRI 7, Isolated from
Tamarins and Belonging to Four Putative Novel Bifidobacterium Species.
AB - Bifidobacterium sp. strains TRE 1, TRE D, TRE H, and TRI 7 were isolated from two
tamarins housed in Parco Natura Viva, Garda Zoological Park S.r.l. (Bussolengo,
Verona, Italy). These strains belong to four putative novel species of the genus
Bifidobacterium The genome sizes were 2.7 Mb for TRE 1, 2.7 Mb for TRE D, 2.4 Mb
for TRE H, and 2.7 Mb for TRI 7. The average GC contents were 63.18% for TRE 1,
58.27% for TRE D, 57.11% for TRE H, and 63.79% for TRI 7.
PMID- 29348340
TI - Complete Genome Sequence of Bacillus methylotrophicus Strain NKG-1, Isolated from
the Changbai Mountains, China.
AB - We report here the complete genome sequence of Bacillus methylotrophicus NKG-1,
isolated from rare dormant volcanic soils on the Changbai Mountains in China. The
4.20-Mb genome contains 4,432 genes and has a G+C content of 47.06%.
PMID- 29348341
TI - Draft Genome Sequence of Escherichia coli Strain SN137, a Bacterium with
Extracellular Proteolytic Activity on Immunoglobulins and Persistence in Human
Tissue Blood.
AB - The draft genome sequence of Escherichia coli strain SN137 is reported here. The
genome comprises 172 contigs, corresponding to 4.9 Mb with 50% G+C content, and
contains several genes related to pathogenicity that explain its survival in
human hematic tissue.
PMID- 29348342
TI - Draft Genome Sequence of the Crude Oil-Degrading and Biosurfactant-Producing
Strain Cobetia sp. QF-1.
AB - We report here the draft genome of Cobetia sp. QF-1, a cold-adapted bacterium
isolated from crude oil-contaminated seawater of the Yellow Sea, China. This
genome is approximately 4.1 Mb (G+C content, 57.44%) with 3,513 protein-coding
sequences. Cobetia sp. QF-1 shows crude oil degradation and biosurfactant
production activity at low temperature.
PMID- 29348343
TI - Draft Genome Sequence of Coxiella burnetii Historical Strain Leningrad-2,
Isolated from Blood of a Patient with Acute Q Fever in Saint Petersburg, Russia.
AB - This is the announcement of a draft genome sequence of Coxiella burnetii strain
Leningrad-2, phase I. The strain, which is mildly virulent in infected guinea
pigs, was isolated in 1957 from the blood of a patient with acute Q fever in
Leningrad (now Saint Petersburg), Russia.
PMID- 29348345
TI - Draft Genome Sequence of Vibrio parahaemolyticus Strain M1-1, Which Causes Acute
Hepatopancreatic Necrosis Disease in Shrimp in Vietnam.
AB - We report here the genome sequence of Vibrio parahaemolyticus strain M1-1, which
causes a mild form of shrimp acute hepatopancreatic necrosis disease (AHPND).
Compared to other virulent strains, the M1-1 genome appeared to express several
additional genes, while some genes were missing. These instabilities may be
related to the reduced virulence of M1-1.
PMID- 29348344
TI - Draft Genome Sequence of Bacillus velezensis OSY-S3, a Producer of Potent
Antimicrobial Agents Active against Bacteria and Fungi.
AB - Bacillus velezensis OSY-S3 produces anti-Listeria, anti-Escherichia coli, and
antifungal compounds. Additionally, fermentate of B. velezensis OSY-S3 culture
removes Staphylococcus aureus biofilms effectively. The draft genome sequence of
B. velezensis OSY-S3 reported here had a genome size of ~3.90 Mb and a G+C
content of 46.5%.
PMID- 29348346
TI - Draft Genome Sequence of Streptococcus canis Clinical Strain TA4, Harboring the M
Like Protein Gene and Isolated in Japan from a Patient with Bacteremia.
AB - Streptococcus canis is an animal-origin beta-hemolytic bacterium that can cause
severe infections in animals and occasionally infects humans. Here, we report a
draft genome sequence of an S. canis strain harboring the M-like protein gene.
This strain was isolated from a patient with bacteremia (reported by Taniyama et
al. [D. Taniyama, Y. Abe, T. Sakai, T. Kikuchi, and T. Takahashi, IDCases 7:48
52, 2017, https://doi.org/10.1016/j.idcr.2017.01.002]). The draft genome
comprises 2,129,080 bp in 60 contigs.
PMID- 29348347
TI - Completed Genome Sequences of Strains from 36 Serotypes of Salmonella.
AB - We report here the completed closed genome sequences of strains representing 36
serotypes of Salmonella These genome sequences will provide useful references for
understanding the genetic variation between serotypes, particularly as references
for mapping of raw reads or to create assemblies of higher quality, as well as to
aid in studies of comparative genomics of Salmonella.
PMID- 29348348
TI - Whole-Genome Sequence of a Mycobacterium goodii Isolate from a Pediatric Patient
in South Africa.
AB - We describe here the draft genome sequence of a Mycobacterium goodii isolate from
a pediatric patient in Western Cape, South Africa. To our knowledge, this is the
second reported genome of this rapidly growing nontuberculous mycobacterial
species.
PMID- 29348349
TI - Complete Genome Sequence of Streptomyces Bacteriophage Abt2graduatex2.
AB - The Streptomyces bacteriophage Abt2graduatex2 is a double-stranded DNA (dsDNA)
Siphoviridae isolated from soil collected in Baltimore, MD, and harvested using
Streptomyces griseus subsp. griseus Abt2graduatex2, a cluster BG phage, encodes
an HicA-like toxin.
PMID- 29348350
TI - Draft Genome Sequences of 14 Strains of Pseudomonas Isolated from Prunus sp.
Plants.
AB - We present here the draft genome sequences of 14 Pseudomonas strains isolated
from Prunus sp. plants in New Zealand and overseas. These new genomic data will
be used to improve the detection of Pseudomonas strains found in imported plant
material at the New Zealand border, improving the time involved in the process of
biosecurity decision-making.
PMID- 29348351
TI - Complete Genome Sequence of the Halophilic Methylotrophic Methanogen Archaeon
Methanohalophilus portucalensis Strain FDF-1T.
AB - We report here the complete genome sequence (2.08 Mb) of Methanohalophilus
portucalensis strain FDF-1T, a halophilic methylotrophic methanogen isolated from
the sediment of a saltern in Figeria da Foz, Portugal. The average nucleotide
identity and DNA-DNA hybridization analyses show that Methanohalophilus mahii, M.
halophilus, and M. portucalensis are three different species within the
Methanosarcinaceae family.
PMID- 29348352
TI - Complete Genome Sequence of Lacinutrix venerupis DOK2-8 Isolated from Marine
Sediment from the East Sea, Republic of Korea.
AB - Lacinutrix venerupis has recently been considered a potential fish pathogen.
Here, we report the complete genome sequence of L. venerupis DOK2-8, which
possesses several virulence-related genes. This strain may be potentially
virulent to other marine organisms, and its genomic information will provide
important insights into the biodiversity of the genus Lacinutrix.
PMID- 29348353
TI - Next-Generation Sequencing Reveals the First Complete Genome Sequence of Cowpea
aphid-borne mosaic virus from Uganda.
AB - We present here the first complete genome sequence of Cowpea aphid-borne mosaic
virus (CABMV) isolated from cowpea in Uganda and compare it with five CABMV
complete genome sequences from Brazil (2), India (2), and Zimbabwe (1). It most
resembled the genomes of two Brazilian isolates (MG-Avr and BR1) and one Indian
isolate (RR3).
PMID- 29348354
TI - Genome Sequence of Enterococcus mundtii EM01, Isolated from Bombyx mori Midgut
and Responsible for Flacherie Disease in Silkworms Reared on an Artificial Diet.
AB - The whole genome sequence of Enterococcus mundtii strain EM01 is reported here.
The isolate proved to be the cause of flacherie in Bombyx mori To date, the
genomes of 11 other E. mundtii strains have been sequenced. EM01 is the only
strain that displayed active pathological effects on its associated animal
species.
PMID- 29348355
TI - Genome Sequence of Trypanosoma cruzi Strain Bug2148.
AB - Trypanosoma cruzi belongs to the group of mitochondrion-containing eukaryotes and
has a highly plastic genome, unusual gene organization, and complex mechanisms
for gene expression (polycistronic transcription). We report here the genome
sequence of strain Bug2148, the first genomic sequence belonging to cluster TcV,
which has been related to vertical transmission.
PMID- 29348356
TI - Draft Genome Sequence of Fusarium fujikuroi, a Fungus Adapted to the Fuel
Environment.
AB - Fusarium fujikuroi isolate FUS01 is highly adapted to grow in jet fuel with
predicted genes involved in hydrocarbon catabolism and carbon assimilation. The
draft genome size is estimated at 49 Mb containing 18,578 proteins with high
similarity to that of F. fujikuroi isolate B14.
PMID- 29348357
TI - Draft Genome Sequence of Bacillus subtilis 2C-9B, a Strain with Biocontrol
Potential against Chili Pepper Root Pathogens and Tolerance to Pb and Zn.
AB - Bacillus subtilis 2C-9B, obtained from the rhizosphere of wild grass, exhibits
inhibition against root rot causal pathogens in Capsicum annuum, Pb and Zn
tolerance, and plant growth promotion in medium supplemented with Pb. The genome
of B. subtilis 2C-9B was sequenced and the draft genome assembled, with a length
of 4,215,855 bp and 4,723 coding genes.
PMID- 29348358
TI - Complete Genome Sequence of Kyrpidia sp. Strain EA-1, a Thermophilic Knallgas
Bacterium, Isolated from the Azores.
AB - Kyrpidia sp. strain EA-1 is a thermophilic hydrogen-oxidizing bacterium isolated
from hydrothermal systems at Sao Miguel Island, Portugal. Here, we present the
complete genome sequence of the strain assembled to a single circular chromosome.
The genome spans 3,352,175 bp, with a GC content of 58.7%.
PMID- 29348359
TI - Complete Genome Sequence of the Type Strain of Macrococcus canis.
AB - The first complete genome sequence of the recently described Macrococcus canis
species has been determined for the strain KM45013T (=DSM 101690T = CCOS 969T =
CCUG 68920T = CCM 8748T). The strain was isolated from a dog with rhinitis and
contains a putative gamma-hemolysin and a mecB-carrying staphylococcal cassette
chromosome mec element (SCCmecKM45013).
PMID- 29348360
TI - Complete Genome Sequences of Three Moraxella osloensis Strains Isolated from
Human Skin.
AB - Here, we present the complete whole-genome sequences of three Moraxella osloensis
strains with octylphenol polyethoxylate-degrading abilities. These strains were
isolated from human skin.
PMID- 29348361
TI - Complete Genome Sequence of Paracoccus yeei TT13, Isolated from Human Skin.
AB - Paracoccus yeei TT13 was isolated from human skin because of its ability to
degrade propylene glycol. Here, we present the whole-genome sequence of this
strain; it possesses one 3.58-Mb chromosome and six plasmids. TT13 genome
analysis indicated that this bacterium has denitrification potential.
PMID- 29348362
TI - Draft Genome Sequence of a Multistress-Tolerant Yeast, Pichia kudriavzevii NG7.
AB - Pichia kudriavzevii NG7 is a multistress-tolerant yeast, isolated from grape
skins. Here, we report the draft genome sequence of P. kudriavzevii NG7, to
understand its biochemical regulation and metabolic pathways.
PMID- 29348363
TI - Atomic-resolution transmission electron microscopy of electron beam-sensitive
crystalline materials.
AB - High-resolution imaging of electron beam-sensitive materials is one of the most
difficult applications of transmission electron microscopy (TEM). The challenges
are manifold, including the acquisition of images with extremely low beam doses,
the time-constrained search for crystal zone axes, the precise image alignment,
and the accurate determination of the defocus value. We develop a suite of
methods to fulfill these requirements and acquire atomic-resolution TEM images of
several metal organic frameworks that are generally recognized as highly
sensitive to electron beams. The high image resolution allows us to identify
individual metal atomic columns, various types of surface termination, and
benzene rings in the organic linkers. We also apply our methods to other electron
beam-sensitive materials, including the organic-inorganic hybrid perovskite
CH3NH3PbBr3.
PMID- 29348364
TI - Building superlattices from individual nanoparticles via template-confined DNA
mediated assembly.
AB - DNA programmable assembly has been combined with top-down lithography to
construct superlattices of discrete, reconfigurable nanoparticle architectures on
a gold surface over large areas. Specifically, the assembly of individual
colloidal plasmonic nanoparticles with different shapes and sizes is controlled
by oligonucleotides containing "locked" nucleic acids and confined environments
provided by polymer pores to yield oriented architectures that feature tunable
arrangements and independently controllable distances at both nanometer- and
micrometer-length scales. These structures, which would be difficult to construct
by other common assembly methods, provide a platform to systematically study and
control light-matter interactions in nanoparticle-based optical materials. The
generality and potential of this approach are explored by identifying a broadband
absorber with a solvent polarity response that allows dynamic tuning of visible
light absorption.
PMID- 29348366
TI - Structures of human PRC2 with its cofactors AEBP2 and JARID2.
AB - Transcriptionally repressive histone H3 lysine 27 methylation by Polycomb
repressive complex 2 (PRC2) is essential for cellular differentiation and
development. Here we report cryo-electron microscopy structures of human PRC2 in
a basal state and two distinct active states while in complex with its cofactors
JARID2 and AEBP2. Both cofactors mimic the binding of histone H3 tails. JARID2,
methylated by PRC2, mimics a methylated H3 tail to stimulate PRC2 activity,
whereas AEBP2 interacts with the RBAP48 subunit, mimicking an unmodified H3 tail.
SUZ12 interacts with all other subunits within the assembly and thus contributes
to the stability of the complex. Our analysis defines the complete architecture
of a functionally relevant PRC2 and provides a structural framework to understand
its regulation by cofactors, histone tails, and RNA.
PMID- 29348365
TI - Detection and localization of surgically resectable cancers with a multi-analyte
blood test.
AB - Earlier detection is key to reducing cancer deaths. Here, we describe a blood
test that can detect eight common cancer types through assessment of the levels
of circulating proteins and mutations in cell-free DNA. We applied this test,
called CancerSEEK, to 1005 patients with nonmetastatic, clinically detected
cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or
breast. CancerSEEK tests were positive in a median of 70% of the eight cancer
types. The sensitivities ranged from 69 to 98% for the detection of five cancer
types (ovary, liver, stomach, pancreas, and esophagus) for which there are no
screening tests available for average-risk individuals. The specificity of
CancerSEEK was greater than 99%: only 7 of 812 healthy controls scored positive.
In addition, CancerSEEK localized the cancer to a small number of anatomic sites
in a median of 83% of the patients.
PMID- 29348369
TI - [History of Researches on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome].
AB - Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease
characterized by chronic, profound, disabling, and unexplained fatigue. The first
patient with ME/CFS in Japan was identified and described in 1990 by Prof. Teruo
Kitani and Dr. Hirohiko Kuratsune of the Research Institute for Microbial
Diseases, Osaka University. Since then, a variety of studies have been performed
to determine the objective biomarkers of the disease. Although it is hypothesized
that brain inflammation is involved in the pathophysiology of ME/CFS, there is to
date no direct evidence of neuroinflammation in patients with ME/CFS. Our recent
positron emission tomography study successfully demonstrated that microglial
activation, which is linked to neuroinflammation, occurs in widespread brain
areas in patients with ME/CFS, and is associated with the severity of the
neuropsychological symptoms. Thus, evaluation of neuroinflammation in patients
with ME/CFS may be essential for understanding the core pathophysiology of the
disease, and for developing objective diagnostic criteria and effective medical
treatments for ME/CFS. Here, we describe disease-related pathophysiological
findings and topics, and discuss the history of the diagnostic and therapeutic
attempts based on previous findings in Japan.
PMID- 29348368
TI - Defining the physiological role of SRP in protein-targeting efficiency and
specificity.
AB - The signal recognition particle (SRP) enables cotranslational delivery of
proteins for translocation into the endoplasmic reticulum (ER), but its full in
vivo role remains incompletely explored. We combined rapid auxin-induced SRP
degradation with proximity-specific ribosome profiling to define SRP's in vivo
function in yeast. Despite the classic view that SRP recognizes amino-terminal
signal sequences, we show that SRP was generally essential for targeting
transmembrane domains regardless of their position relative to the amino
terminus. By contrast, many proteins containing cleavable amino-terminal signal
peptides were efficiently cotranslationally targeted in SRP's absence. We also
reveal an unanticipated consequence of SRP loss: Transcripts normally targeted to
the ER were mistargeted to mitochondria, leading to mitochondrial defects. These
results elucidate SRP's essential roles in maintaining the efficiency and
specificity of protein targeting.
PMID- 29348367
TI - A pathway for mitotic chromosome formation.
AB - Mitotic chromosomes fold as compact arrays of chromatin loops. To identify the
pathway of mitotic chromosome formation, we combined imaging and Hi-C analysis of
synchronous DT40 cell cultures with polymer simulations. Here we show that in
prophase, the interphase organization is rapidly lost in a condensin-dependent
manner, and arrays of consecutive 60-kilobase (kb) loops are formed. During
prometaphase, ~80-kb inner loops are nested within ~400-kb outer loops. The loop
array acquires a helical arrangement with consecutive loops emanating from a
central "spiral staircase" condensin scaffold. The size of helical turns
progressively increases to ~12 megabases during prometaphase. Acute depletion of
condensin I or II shows that nested loops form by differential action of the two
condensins, whereas condensin II is required for helical winding.
PMID- 29348370
TI - [Diagnosis and Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome].
AB - We present here the Japanese clinical diagnostic criteria for myalgic
encephalomyelitis/chronic fatigue syndrome (ME/CFS) that were proposed in 2016 by
the Japanese Ministry of Health, Labour and Welfare study group. The clinical
diagnosis criteria of ME/CFS were created to be used by healthcare agencies in
charge of primary care practice. We also explain the current prognosis in ME/CFS
and medical treatments used in major medical institutions in Japan.
PMID- 29348371
TI - [Neuroinflammation in the Brain of Patients with Myalgic
Encephalomyelitis/Chronic Fatigue Syndrome].
AB - Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by
chronic, profound, disabling, and unexplained fatigue; cognitive impairment; and
chronic widespread pain. By using positron emission tomography, our study
demonstrated neuroinflammation in the brain of patients with ME/CFS.
Neuroinflammation was found to be widespread in the brain areas of the patients
with ME/CFS and was associated with the severity of their neuropsychological
symptoms. The ongoing research would lead to the establishment of objective
diagnostic criteria and development of an appropriate therapy.
PMID- 29348372
TI - [New Diagnostic Biomarkers for Chronic Fatigue Syndrome].
AB - Chronic fatigue syndrome (CFS) is a persistent and unexplained pathological state
characterized by exertional and severely debilitating fatigue, with/without
symptoms of infection or neuropsychiatric symptoms, and with a minimum duration
of 6 consecutive months. The pathogenesis of CFS is not fully understood. There
are no firmly established diagnostic biomarkers or treatment, due to incomplete
understanding of the etiology of CFS and diagnostic uncertainty. We performed
comprehensive metabolomic analyses of blood samples obtained from patients with
CFS and healthy controls to establish an objective diagnosis of CFS. Here, we
review previous findings concerning the immune, endocrine, and metabolic system
in animal models for CFS and the patients, and present our results which may
contribute to the development of a diagnostic biomarker for CFS.
PMID- 29348373
TI - [Immunopathogenesis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
(ME/CFS)].
AB - A recent study on the pathogenesis of myalgic encephalomyelitis/chronic fatigue
syndrome (ME/CFS) has revealed an elevation of inflammatory and anti-inflammatory
cytokines in the sera and cerebrospinal fluids of the patients and presence of
autoantibodies in subgroups of ME/CFS patients. Furthermore, investigator
initiated clinical trials have proved the efficacy of anti-CD20 antibody
(rituximab), that eliminate B cells, in the treatment of ME/CFS. Based on these
findings, we hypothesize that immune abnormalities, such as enhanced autoimmune
responses, may play an essential role in the neuroinflammatory pathogenesis of
ME/CFS.
PMID- 29348374
TI - [Neurologic Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome:
A Review].
AB - Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an illness
characterized by fatigue lasting for at least six months, post-exertional
malaise, unrefreshing sleep, cognitive impairment and orthostatic intolerance.
ME/CFS has been a controversial illness because it is defined exclusively by
subjective complaints. However, recent studies of neuroimaging as well as
analysis of blood markers, energy metabolism and mitochondrial function have
revealed many objective biological abnormalities. Specifically, it is suspected
that the symptoms of ME/CFS may be triggered by immune activation - either inside
or outside the brain - through release of inflammatory cytokines. In this review,
we summarize potentially important recent findings on ME/CFS, focusing on
objective evidence.
PMID- 29348375
TI - [Suspected Non-Alzheimer's Disease Pathophysiology (SNAP) and Its Pathological
Backgrounds in the Diagnosis of Preclinical and Clinical Alzheimer's Disease].
AB - Suspected non-Alzheimer's disease pathophysiology (SNAP) is a biomarker-based
condition that is found in individuals with normal levels of amyloid-beta protein
(Abeta) markers (A-) and abnormal levels of markers of neurodegeneration or
neuronal injury (N+). SNAP is found in 20-26% of cognitively normal (CN)
individuals aged 65 years or older and 17-35% of individuals with mild cognitive
impairment (MCI). Similarly, 7-39% of patients with clinically probable
Alzheimer's disease (AD) dementia are negative for Abeta. The epsilon4 allele of
the apolipoprotein E gene is underrepresented in individuals with SNAP compared
with amyloid-positive (A+) groups. The progression of the cognitive impairments
of individuals with SNAP was slower than that of A+N+ subjects who had a high
likelihood of AD pathophysiology and faster than that of A-N- subjects. The
pathological backgrounds of the individuals with SNAP were heterogeneous and
included cerebrovascular disorders, mixed pathologies, and non-AD
neurodegeneration, such as primary age-related tauopathy [PART, also known as
senile dementia of the neurofibrillary tangle type (SD-NFT) (tangle-only
dementia) at the dementia stage] and argyrophilic grain disease. Further
clarification of SNAP is needed to better define the mechanisms underlying the
progression of AD pathologies in older individuals.
PMID- 29348376
TI - [Benign Outcome of Cochlear Implantation in a Patient with Superficial
Siderosis].
AB - We report the case of a 38-year-old man with gait disorder and hearing loss. The
patient had developed gait disorder due to a cervical meningioma since 4 year-old
disappeared for 15 years after the surgical removal of the meningioma. However,
at the age of 21 year-old, the gait disorder reappeared and worsened
progressively. Sensorineural hearing loss (SNHL) and epileptic seizures developed
during the disease course, and he was diagnosed with superficial siderosis (SS).
When he was 37 years old, he experienced sudden-onset of right-side hearing
impairment and was considered a candidate for cochlear implantation (CI) at the
otorhinolaryngology clinic of the nearby University Hospital. He underwent CI in
November 2014. Eight months after the operation, his right side hearing improved
although ataxia, hearing loss, and pyramidal sign persisted. At the long term
follow-up of 29 months after CI, his hearing remained at the improved level.
Thus, CI may be an effective long-term treatment for SNHL in patients with SS and
could prevent the progression of his hearing loss. (Received February 1, 2017;
Accepted August 23, 2017; Published January 1, 2018).
PMID- 29348377
TI - Are We Ready for National Diabetes Prevention Program?
PMID- 29348378
TI - Analysis of Diabetes Mellitus Determinants in Indonesia: A Study from the
Indonesian Basic Health Research 2013.
AB - BACKGROUND: diabetes mellitus is a silent-killer. Its prevalence and impact on
health expenses increase from year to year. This study aims to investigate the
characteristics and the risk factors that affect diabetes mellitus in Indonesia.
METHODS: this is a cross sectional study. Data were obtained from the Basic
Health Research (RISKESDAS) in 2013. The samples were individuals aged >=15
years, whose fasting blood glucose and 2 hours blood glucose after the imposition
have been measured. 38.052 individuals were selected for this study. The
variables of age, sex, marital status, level of education, employment status,
living area, regional status, hypertension, obesity, smoking habit, and
dyslipidemia are analyzed as risk factors for diabetes mellitus. Bivariate
analysis was using chi-square test with significance level of p<0.05 and
confidence interval (CI) of 95%, and multivariate analysis using multiple
logistic regression test. RESULTS: our study showed that 13% have diabetes
mellitus in 2013. Factors affecting diabetes mellitus were age>55 years (OR=5.10;
95%CI 4.42 to 5.89; p<0.001), female (OR=1.37; 95%CI 1.26 to 1.49; p<0.001),
rural (OR=1.16; 95%CI 1.08 to 1.26; p<0.001), married (OR=1.31; 95%CI 1.07 to
1.58; p<0.05), unemployed (OR=1.14; 96%CI 1.05 to 1.23; p<0.05), obesity
(OR=1.46; 95%CI 1.35 to 1.58; p<0.001), hypertension (OR=1.68; 95%CI 1.55 to
1.81; p<0.001) and dyslipidemia (OR=1.53; 95%CI 1.39- 1.68; P<0.001). CONCLUSION:
as many as 13% of individuals have diabetes mellitus in 2013. Age, gender, living
area, employment status, obesity, hypertension, and dyslipidemia are the
contributing factors to diabetes mellitus.
PMID- 29348379
TI - The Differences in Serum Quantitative Specific IgE Levels Induced by
Dermatophagoides pteronyssinus, Dermatophagoides farinae and Blomia tropicalis
Sensitization in Intermittent and Persistent Allergic Asthma.
AB - BACKGROUND: house dust mites (HDM) are an important inhalant allergen in allergic
asthma. However, molecular diagnostic study of specific IgE to HDM allergens has
not been done in Indonesia. In addition, the association of quantitative specific
IgE measurement with asthma severity has not been investigatedd. This study aimed
to investigate the difference of serum quantitative specific IgE levels induced
by Dermatophagoides (D.) pteronyssinus, D. farinae and Blomia tropicalis
sensitization in intermittent and persistent allergic asthma. METHODS: this was a
cross-sectional study on adult allergic asthma patients who were invited for
serum specific IgE testing. This study was a part of a larger study within the
Division of Allergy and Immunology, Cipto Mangunkusumo Hospital. Asthma severity
was defined based on Global Initiative on Asthma (GINA) 2015 criteria and were
grouped as intermittent or persistent. Quantitative specific IgE testing was done
on blood serum using a multiple allergosorbent test (Polycheck Allergy, Biocheck
GmbH, Munster, Germany). The HDM allergens tested were D. pteronyssinus, D.
farinae, and Blomia tropicalis. Difference between two groups were analyze using
Mann-Whitney test. RESULTS: a total of 87 subjects were enrolled in this study;
69 (79.3%) were women. Mean patients' age was 40, 2 years. Sixty-three (72.4%)
subjects had asthma and allergic rhinitis. Fifty-eight (66.7%) subjects were
classified as persistent asthma. The prevalence of sensitization was 62.1% for D.
farinae, 51.7% for D. pteronyssinus, and 48.3% for Blomia tropicalis. The median
of specific IgE levels were significantly higher in persistent asthma compares to
intermittent asthma induced by D. farinae (median 1.30 vs. 0.0 kU/L; p=0.024) and
B. tropicalis (median 0.57 vs. 0.0 kU/L; p=0.015) sensitization. Level of
Specific IgE D. pteronyssinus was also to be higher in persistent asthma than
the level measured in intermittent asthma (0.67 vs. 0.00 kU/L; p=0.066).
CONCLUSION: Sensitization of HDM allergens was shown to be highest for D. farinae
62.1%, followed by D. pteronyssinus 51.7% and Blomia tropicalis 48.3%. Specific
IgE level induced by D. farinae and Blomia tropicalis sensitization were
significantly higher in patients with persistent asthma compared to intermittent
asthma, whereas specific IgE level induced by D. pteronyssinus sensitization was
higher in persistent asthma although not statistically significant.
PMID- 29348380
TI - Effect of Nigella sativa Seed Extract for Hypertension in Elderly: a Double
blind, Randomized Controlled Trial.
AB - BACKGROUND: Nigella sativa (NS) seed extract shows diuretic activity, inhibits
sympathetic nervous system overactivity and increases the production of Nitric
Oxide in in vivo studies, thus it has a potential use as an adjuvant
antihypertensive for elderly population. This study aimed to determine the effect
of Nigella sativa seed extract to systolic blood pressure (SBP) and diastolic
blood pressure (DBP) of elderly patients with hypertension. METHODS: a double
blind, randomized controlled trial was conducted on elderly subjects with
hypertension in three outpatient clinics in Cipto Mangunkusumo National Hospital
Jakarta Indonesia from June to September 2011. Subjects were divided into
intervention group given 300 mg Nigella sativa seed extract twice daily for 28
days and into another group which was given placebo. Blood pressure were measured
on day 1 and 28. Intention to treat analysis using unpaired t-test to compare
blood pressure after intervention between the two groups was performed. RESULTS:
of a total of 85 patients, 76 subjects fulfilled the study criteria and were
randomized into 2 groups, with 38 subjects in each group. Both groups were
comparable in all important prognostic factors. The mean systolic blood pressure
of the NS group was decreased from 160.4 (SD 15.7) mmHg to 145.8 (SD 19.8) mmHg,
and from 160.9 (16.3) mmHg to 147.53 (SD 22.0) mmHg in the placebo group
(p=0.36). The mean diastolic blood pressure in the NS group was decreased from
78.3 (SD 11.9) to 74.4 (SD 8.2) mmHg, and from 79.0 (SD 12.4) to 78.2 (SD 8.9) in
the placebo group (p=0.35). Reported adverse events include dyspepsia in 6
subjects (15.7%), nausea in 3 subjects (7.8%), and constipation in 2 subjects
(5.2%). No electrolyte abnormalities, liver and renal toxicities, or orthostatic
hypotension were observed. CONCLUSION: although a trend towards a slight decrease
in blood pressure was observed, Nigella sativa has not been proven to be
effective in reducing blood pressure in elderly patients with hypertension.
PMID- 29348381
TI - Thyroid Dysfunction in Type 2 Diabetes Mellitus Patients.
AB - BACKGROUND: thyroid dysfunction is more likely to occur in diabetes mellitus
patients than general population. Until now, no study has been done to find
prevalence of hypothyroidism and hyperthyroidism in Indonesian diabetics. This
study aimed to find the proportion and characteristics of thyroid dysfunction in
Indonesian type 2 diabetes mellitus patients. METHODS: a cross-sectional study
was conducted in Endocrine and Diabetes Polyclinic, Department of Internal
Medicine, Cipto Mangunkusumo Hospital from July to September 2015. This study
include type 2 diabetes mellitus patients, age >= 18 year-old, willing to undergo
thyroid laboratory testing. In this study, hypothyroidism defined as TSH more
than 4.0 mIU/L, while hyperthyroidism is defined as TSH less than 0.4 mIU/L with
eCLIA. RESULTS: from 364 subjects who were recruited from Endocrine and Diabetes
Polyclinic, Cipto Mangunkusumo Hospital, 303 subjects underwent this study until
analysis. Two hundred and three (273) subjects (90.1%) were euthyroid, 7 subjects
(2.31%) were hyperthyroid, and 23 subjects (7.59%) were hypothyroid. Majority of
the patients had subclinical hypothyroidism (56.5% based on Zulewski and
Billewicz Score and 65.2% based on fT4 laboratory result), while 42.9% and 71.4%
subjects had clinical hyperthyroidism based on clinical appearance and fT4
laboratory result respectively. CONCLUSION: proportion of hypothyroidism was
7.59% and hyperthyroidism was 2.31%, while the proportion of total thyroid
dysfunction was 9.9% among diabetics. It is suggested that screening for thyroid
dyscfunction can be done in high risk condition as a part of comprehensive
management in type 2 diabetes mellitus patients.
PMID- 29348382
TI - The Effect of Ophiocephalus striatus Extract on the Levels of IGF-1 and Albumin
in Elderly Patients with Hypoalbuminemia.
AB - BACKGROUND: a freshwater fish Ophiocephalus striatus or known locally to
Indonesian as haruan,can potentially increases IGF-1 and albumin levels in
elderly patients with hypoalbuminemia due to the contents of amino acids, fatty
acids, vitamins, and minerals. This study was conducted to investigate the effect
of Ophiocephalus striatus extract on the level of IGF-1 and albumin in elderly
patients with hypoalbuminemia. METHODS: the study is a double-blind randomized
controlled trial involving malnourished elderly inpatients (>=60 years old)
recovering from acute condition before hospital discharge, with Mini Nutritional
Assessment score <=23.5 and albumin level <3.5 g/dL. A total of 109 subjects were
randomly divided into two groups: one group received 10 g Ophiocephalus striatus
extract per day for 14 days and another group received placebo. Albumin and IGF-1
levels were obtained before and after intervention. RESULTS: ninety subjects
completed the study (extract group=45 subjects; placebo group =45 subjects) for
14 days. The median of age were 69 (64;75) years and the male to female ratio
were 2 : 3. The changes of IGF-1 and albumin levels from before to after
intervention between extract group compared to placebo group were 14.7
(0.30;31.5) ng/mL vs 1.0 (-6;13.15) ng/mL (p=0.002) and 0.5 (0.15;0.70) g/dL vs
0.10 (0.0;0.50) g/dL (p=0.003), respectively. There were significant differences
in the improvement of IGF-1 and albumin levels between extract and placebo group.
CONCLUSION: supplementation of Ophiocephalus striatus extract was associated with
a significant increase in IGF-1 and albumin levels in elderly patients with
hypoalbuminemia.
PMID- 29348383
TI - Improving Diagnostic of Pulmonary Tuberculosis in HIV Patients by Bronchoscopy: A
Cross Sectional Study.
AB - BACKGROUND: diagnostic of pulmonary TB in HIV patients is a problem due to non
specific clinical features, or radiological appearance. HIV patients with
CD4<=200 cells/mL infected with M. tuberculosis have less capacity in containing
M. tuberculosis, developing granulomas, casseous necrosis, or cavities. This
condition is caused by weakend inflammatory which later reduced sputum production
and may cause false negative result. This study aimed to assess differences in
the positivity level of acid fast bacilli (AFB) and cultures of M. tuberculosis
from non-bronchoscopic sputum (spontaneous and induced sputum) compared to
bronchoscopic sputum (bronchoalveolar lavage) in HIV positive patients suspected
pulmonary tuberculosis with CD4<200 cells/MUL. METHODS: this cross sectional
study was conducted in adult HIV patients treated in Hasan Sadikin Hospital with
CD4<=200 cells/MUL suspected with pulmonary tuberculosis by using paired
comparative analytic test. All patients expelled sputum spontaneously or with
sputum induction on the first day. On the next day, bronchoalveolar lavage (BAL)
was performed. The two samples obtained from two methods were examined by AFB
examination with staining Ziehl Neelsen (ZN) and cultured of M. tuberculosis on
solid media Ogawa on all patients. Positivity, sensitivity and increased
sensitivity of AFB and culture of M. tuberculosis in the non bronchoscopic and
bronchoscopic groups were compared. RESULTS: there were differences in the
positivity level of AFB with ZN staining between non-bronchoscopic and
bronchoscopic groups which were 7/40 (17.5%) vs 20/40 (50.0%) (p<0.001). The
differences between the cultures of non-bronchoscopic and bronchoscopic groups
were 16/40 (40.0%) vs 23/40 (57.5%) (p=0.039). Bronchoscopic sputum increased the
positivity level of the ZN AFB examination by 32.5% (from 17.5% to 50.0%) as well
as on culture examination by 17.5% (from 40.0% to 57.5%). CONCLUSION:
Bronchoalveolar lavage can improve the positivity level of smears and cultures in
patients suspected of pulmonary TB in HIV patients with CD4<200 cells/MUL.
PMID- 29348384
TI - Clinical Outcomes of Geriatric Care in Cipto Mangunkusumo Hospital, Before and
After the Implementation of National Health Insurance Program.
AB - BACKGROUND: the National Health Insurance (NIH/JKN) has been enacted since
January 2014. Various outcomes of geriatric patient care, such as improved
functional status and quality of life have not been evaluated. Prolonged
hospitalization and re-hospitalization are potentially affecting the efficiency
care of this vulnarable group. This study aimed to identify the differences of
functional status improvement, quality of life improvement, length of stay, and
hospitalization of geriatric patients admitted to CMH between prior to and after
NHI implementation. METHODS: a cohort study with historical control was conducted
among geriatric patients admitted to Acute Geriatric Ward CMH Hospital on two
periods of time: January-December 2013 (pre-NHI implementation) and June 2014-May
2015 (after NHI implementation). Patients who died within 24 hours of hospital
admission, those with APPACHE II score >24, advance stage cancer, transfer to
other wards before they were discharged or have incomplete record were excluded
from the study. Data on demographical and clinical characteristics, functional
status, quality of life, length of stay, and re-hospitalization were taken from
patient's medical record. The differences of studied outcomes were analyzed using
t-test or Mann-Whitney test. RESULTS: there were 102 subjects in pre-NHI and 135
subjects in NHI groups included in the study. Median lengths of stay were not
different between two groups (12.5 days in pre-NHI and 10 days in NHI groups,
p=0.087), although the proportion of patients with in-hospital stay less than 14
days was higher in NHI group. The difference of functional status of discharged
patients in pre-NHI and NHI groups were 3 and 3 (p=0.149) respectively, whereas
for health-related quality of life, although NHI group in the beginning showed a
lower quality of life compared to the pre-NHI (0.163 [0.480] vs. 0.243 [0.550];
p=0.012). However, after incorporating comprehensive geriatric assessment (CGA)
the quality of life improved significantly by the end of in-hospital care in both
groups. Re-hospitalization incidence in NHI group was lower compared to pre-NHI
(7 [5.2%] vs. 13 [12.7%]; p=0.038). CONCLUSION: our study shows that there was
no significant difference regarding length of stay, functional status, and
health-related quality of life between prior to and after national health
insurance implementation on admitted geriatric patients. Rehospitalization
incidence showed better results in NHI group and hence NHI implementation is
favored.
PMID- 29348385
TI - A Rare Case Series of Ischemic Stroke Following Russell's Viper Snake Bite in
India.
AB - Snakebite is an important medical problem in India. Among their various
manifestations, cerebral complications are uncommonly found in literature.
Moreover, Ischemic stroke following snake bite is quite rare. Here we report a
case series of two such cases that developed neurological manifestations
following Russell's viper bite. On computerized tomography (CT) scan of brain;
cerebral infarcts were revealed. Their likely mechanisms are discussed in present
study which include disseminated intravascular coagulation, toxin induced
vasculitis and endothelial damage.
PMID- 29348386
TI - ST Elevation in Lead aVR and Its Association with Clinical Outcomes.
AB - The purpose of this case repots are to evaluate the role of ST elevation in aVR
lead and to make analysis between both cases. There are some atypical
electrocardiogram (ECG) presentations which need prompt management in patient
with ischemic clinical manifestation such as ST elevation in aVR lead. In this
case study, we report a 68-year old woman with chief symptoms of shortness of
breath and chest discomfort. She was diagnosed with cardiogenic shock, with
Killip class IV, and TIMI score of 8. The second case is a 57-year-old man with
typical chest pain at rest which could not be relieved with nitrate treatment. He
was diagnosed with ST elevation in inferior and aVR lead, and occlusion in left
circumflex artery (LCX). Both patients underwent primary percutaneous coronary
intervention (PPCI). Subsequently, both cases presented remarkable clinical
improvements and improved ST elevation myocardial infarction (STEMI) in aVR lead.
PMID- 29348387
TI - Cancer Stem Cells and Molecular Biology Test in Colorectal Cancer: Therapeutic
Implications.
AB - Colorectal cancer (CRC) is the third most frequent cancer in males, the second in
females, and is the second leading cause of cancer related death worldwide.
Within Indonesia's 250 million population, the incidence rates for CRC per
100,000 population were 15.2 for males and 10.2 for females, and estimated 63,500
cases per year. More than 50% of colorectal cancer patients will develop
metastasis. CRC is still the main cause of tumor-related death, and although most
CRC patients are treated with surgery to remove the tumor tissue, some of the CRC
patients recurred. Chemotherapy used as adjuvant or neoadjuvant therapy also has
several problems, in which these treatments are useless in tumor cells with chemo
resistance. Molecular testing of CRC from tumor tissues has important
implications for the selection of treatment. Biomarkers can be used as prognostic
value, molecular predictive factors, and targeted therapy. Recent research
reported that, cancer stem cells (CSCs) are considered as the origin of
tumorigenesis, development, metastasis and recurrence. At present, it has been
shown that CSCs existed in many tumors including CRC. This review aims to
summarize the issue on CSCs, and the future development of drugs that target
colorectal cancer stem cells.
PMID- 29348388
TI - Disseminated Histoplasmosis in an Indonesian HIV-Positive Patient: A Case
Diagnosed by Fine Needle Aspiration Cytology.
AB - A 30-year-old Javanese-Indonesian man was admitted with complaints of 3 months
persistent fever, weight loss, and fatigue. He had never known his past history
of unprotected HIV until the admission. His only risk factor is unsafe sex. The
patient seemed well nourished. Physical examination revealed blood pressure
100/60 mmHg, pulse 100 beats per minute, respiratory rate 20 times per minute,
and temperature 38.8 degrees C. Multiple cervical and inguinal lymphadenopathies
were also found. Electrocardiogram showed anterolateral ischemic finding, whereas
chest X-ray were normal. Laboratory test results revealed pancytopenia with
hemoglobin of 8.2 g/dL, leucocyte count 2000 cells/mm3, platelet 78000 cells/mm3,
hematocrit 25.8%, AST 162 IU/L, ALT 81 IU/L, decreased albumin of 2.72 g/dL. The
clinical differential diagnosis were lymphoma or tuberculosis lymphadenopathy.
PMID- 29348389
TI - Efficacy of Curcumin as Adjuvant Therapy to Induce or Maintain Remission in
Ulcerative Colitis Patients: an Evidence-based Clinical Review.
AB - BACKGROUND: treatment guidelines for ulcerative colitis (UC) not yet established.
Currently, mesalazine, corticosteroids, and immunomodulators are treatment
options for UC. However, they are known to have unpleaseant side effects such as
nausea, vomiting, headaches, hepatitis, and male infertility. Curcumin is found
in Turmeric plants (Curcuma longa L.), which possesses both anti-inflammatory and
antioxidant properties. This study aimed to determine whether curcumin as
adjuvant therapy can induce or maintain remission in UC patients. METHODS:
structured search in three database (Cochrane, PubMed, Proquest) using
"Curcumin", "remission" and "Ulcerative Colitis" as keywords. Inclusion criteria
is randomized controlled trials (RCTs), meta-analysis, or systematic review using
curcumin as adjuvant therapy in adult UC patients. RESULTS: we found 49 articles.
After exclusion, three RCTs were reviewed; two examined curcumin efficacy to
induce remission and one for remision maintenance in UC. Curcumin was
significantly more effective than placebo in all RCTs. The efficacy of curcumin
could be explained by its anti-inflammatory properties, which inhibit NF-kB
pathway. Regulation of oxidant/anti-oxidant balance can modify the release of
cytokines. However, methods varied between RCTs. Therefore, they cannot be
compared objectively. Futhermore, the sample size were small (n= 50, 45, 89)
therefore the statistical power was not enough to generate representative results
in all UC patients. CONCLUSION: Available evidence showed that curcumin has the
potential to induce and maintain remission in UC patients with no serious side
effects. However, further studies with larger sample size are needed to recommend
it as adjuvant therapy of ulcerative colitis.
PMID- 29348390
TI - Current and Emerging Therapy on Lupus Nephritis.
AB - Lupus nephritis (LN) is involvement of the kidney in patient with systemic lupus
erythematosus (SLE) and one of the most common target organ in SLE. The diagnosis
of LN will significantly impact the clinical outcome and therapy of the patient.
Therapy regiment of LN is divided into two stages, induction and maintenance
treatment. The main objective of the induction therapy is to achieve complete or
partial remission as soon as possible since it is correlated with better
prognosis and fewer relapse incidence. In the maintenance stage, the main aim of
the therapy is to maintain the remission status and avoid future relapse. It is
also important to evaluate the effectiveness of the therapy as it will affect the
duration and the regiment therapy being used. Corticosteroid, cyclophosphamide,
mycophenolate mofetil, azathrioprine, cyclosporine and tacrolimus are example of
drugs used in LN therapy. Currently, studies are being conducted to evaluate and
develop targeted drug therapy to further add treatment options for LN.
PMID- 29348391
TI - Effects of senescence and angiotensin II on expression and processing of amyloid
precursor protein in human cerebral microvascular endothelial cells.
AB - The present study was designed to determine the effects of senescence and
angiotensin II (Ang II) on expression and processing of amyloid precursor protein
(APP) in human brain microvascular endothelial cells (BMECs). Senescence caused a
decrease in APP expression thereby resulting in reduced secretion of soluble
APPalpha (sAPPalpha). In contrast, beta-site APP cleaving enzyme (BACE1)
expression and production of amyloid beta (Abeta)40 were increased in senescent
endothelium. Importantly, in senescent human BMECs, treatment with BACE1
inhibitor IV inhibited Abeta generation and increased sAPPalpha production by
enhancing a disintegrin and metalloprotease (ADAM)10 expression. Furthermore, Ang
II impaired expression of ADAM10 and significantly reduced generation of
sAPPalpha in senescent human BMECs. This inhibitory effect of Ang II was
prevented by treatment with BACE1 inhibitor IV. Our results suggest that
impairment of alpha-processing and shift to amyloidogenic pathway of APP
contribute to endothelial dysfunction induced by senescence. Loss of sAPPalpha in
senescent cells treated with Ang II exacerbates detrimental effects of senescence
on APP processing. Notably, inhibition of BACE1 has beneficial effects on
senescence induced endothelial dysfunction. Reported findings may help to explain
contributions of senescent cerebral microvascular endothelium to development of
cerebral amyloid angiopathy and Alzheimer's disease (AD) pathology.
PMID- 29348392
TI - Rapamycin prevents the intervertebral disc degeneration via inhibiting
differentiation and senescence of annulus fibrosus cells.
AB - The effects of bleomycin and rapamycin on cellular senescence and differentiation
of rabbit annulus fibrosus stem cells (AFSCs) were investigated using a cell
culture model. The results showed that bleomycin induced cellular senescence in
AFSCs as evidenced by senescence-associated secretory phenotype. The morphology
of AFSCs was changed from cobblestone-like cells to pancake-like cells. The
senescence-associated beta-galactosidase activity, the protein expression of P16
and P21, and inflammatory-related marker gene levels IL-1beta, IL-6, and TNF
alpha were increased in bleomycin-treated AFSCs in a dose-dependent manner.
Rapamycin treatment decreased the gene expression of MMP-3, MMP-13, IL-1beta, IL
6, TNF-alpha, and protein levels of P16 and P21 in bleomycin-treated AFSCs.
Furthermore, neither bleomycin nor rapamycin changed the ribosomal S6 protein
level in AFSCs. However, the phosphorylation of the ribosomal S6 protein was
increased in bleomycin-treated AFSCs and decreased in rapamycin-treated AFSCs.
AFSCs differentiated into adipocytes, osteocytes, and chondrocytes when they were
cultured with respective differentiation media. Rapamycin inhibited multi
differentiation potential of AFSCs in a concentration-dependent manner. Our
findings demonstrated that mammalian target of rapamycin (mTOR) signaling affects
cellular senescence, catabolic and inflammatory responses, and multi
differentiation potential, suggesting that potential treatment value of rapamycin
for disc degenerative diseases, especially lower back pain.
PMID- 29348393
TI - Epigenetics: the panacea for cognitive decline?
PMID- 29348394
TI - HOXC6 predicts invasion and poor survival in hepatocellular carcinoma by driving
epithelial-mesenchymal transition.
AB - Aberrant expression of HOXC6 has been reported in several malignant tumors, yet
little is known about the value of HOXC6 in invasion and prognosis of
hepatocellular carcinoma (HCC). HOXC6 expression was positively correlated with
high AFP level, liver cirrhosis, larger tumor, vascular invasion and BCLC stage.
Kaplan-Meier analysis revealed that HOXC6 was an independent predictor for
overall survival (OS) and time to recurrence (TTR). In addition, HOXC6 status
could act as prognostic predictor in different risk subgroups. Moreover, HOXC6
maintained its prognostic value in different ability of invasiveness.
Furthermore, combination of HOXC6 and serum AFP could be a potential predictor
for survival in HCC patients. Additionally, further study showed that HOXC6 may
promote invasion of HCC by driving epithelial-mesenchymal transition (EMT).
Knockdown of HOXC6 significantly decreased the migration and invasion of HCC
cells and changed the expression pattern of EMT markers. An opposite expression
pattern of EMT markers was observed in HOXC6-transfected cells. In addition,
immunohistochemistry and RT-PCR results further confirmed this correlation. In
conclusion, HOXC6 contributes to invasion by inducing EMT pathway and predicts
poor prognosis of HCC. HOXC6/AFP expression may help to distinguish the different
risks of HCC patients after hepatectomy.
PMID- 29348395
TI - NKILA inhibits NF-kappaB signaling and suppresses tumor metastasis.
AB - The long non-coding RNA (lncRNA) NKILA (nuclear transcription factor NF-kappaB
interacting lncRNA) functions as a suppressor in human breast cancer and tongue
cancer. However, the clinical significance and biological roles of NKILA in
esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we
showed that NKILA was downregulated in ESCC tissues and cancer cells compared
with their normal counterparts. Low NKILA expression correlated with large tumor
size and advanced TNM stage, and predicted poor overall and disease-free survival
of ESCC patients. Further loss- and gain-of-function assays indicated that NKILA
inhibited proliferation and migration of ESCC cells in vitro, suppressed tumor
growth and lung metastasis in vivo. Mechanistically, NKILA could inhibit
phosphorylation of IkappaBalpha, suppress p65 nuclear translocation and
downregulate the expression of NF-kappaB target genes in ESCC cells. These
results suggest NKILA could suppress malignant development of ESCC via abrogation
of the NF-kappaB signaling and may potentially serve as a prognostic marker for
ESCC.
PMID- 29348396
TI - A Case of Umbilical Artery Thrombosis in the Third Trimester of Pregnancy.
AB - BACKGROUND Umbilical artery thrombosis is an extremely rare complication during
pregnancy. Umbilical artery thrombosis has a poor prognosis and is associated
with increased rates of perinatal morbidity, including intrauterine growth
restriction (IUGR), and fetal mortality. CASE REPORT We report a rare case of
umbilical artery thrombosis, diagnosed by ultrasound, at 33 weeks gestation in a
30-year-old woman who had previously had an uneventful pregnancy. CONCLUSIONS
Umbilical artery thrombosis is a rare complication of pregnancy that is
associated with high fetal mortality. Management may include planned elective
delivery by cesarean section, following antenatal corticosteroid therapy for
fetal lung maturation.
PMID- 29348397
TI - Placement of an Aortohepatic Conduit as an Alternative to Standard Arterial
Anastomosis in Liver Transplantation.
AB - BACKGROUND The aim of this study was to assess the impact of placement of an
aortohepatic conduit on graft and patient survival after liver transplantation
(LT) in selected patients with an inadequate recipient hepatic artery (HA) for a
standard arterial anastomosis. MATERIAL AND METHODS Of 331 patients who underwent
deceased donor LT, 25 (7.6%) who received placement of an aortohepatic conduit at
the time of transplantation were included. Clinical characteristics and outcomes,
including postoperative complications, conduit patency, and graft and patient
survival rates, were analyzed. RESULTS All 25 patients included in this study
presented a high preoperative Model for End-stage Liver Disease score (25.4+/
8.6; range, 6-42) and high rates of retransplantation (n=11, 44%) or previous
abdominal - pelvic surgery (n=5, 20%). The observed postoperative vascular
complications were portal vein thrombosis in 3 cases (12%) and anastomosis-site
bleeding of the aortohepatic conduit in 1 case (4%); there was no HA thrombosis
or stenosis in our analysis. With a median follow-up of 37 months (range, 0-69
months), all aortohepatic conduits were patent, and the graft and patient
survival rates were 84% and 68%, respectively. The causes of death were graft
failure (n=4), pneumonia (n=3), and cerebrovascular accidents (n=1). CONCLUSIONS
Our results indicate that placement of an aortohepatic conduit is a feasible
alternative to a standard arterial anastomosis in selected patients whose HA and
surrounding potential inflow arteries are not suitable for standard arterial
anastomosis.
PMID- 29348398
TI - Association Study of Polymorphisms in Genes Relevant to Vitamin B12 and Folate
Metabolism with Childhood Autism Spectrum Disorder in a Han Chinese Population.
AB - BACKGROUND Both genetic and environmental factors play a role in the development
of autism spectrum disorder (ASD). This case-control study examined the
association between childhood ASD and single-nucleotide polymorphisms (SNPs) in
genes involved with vitamin B12 and folate metabolism. MATERIAL AND METHODS
Genotypes of transcobalamin 2 (TCN2) rs1801198, methionine synthase (MTR)
rs1805087, methionine synthase reductase (MTRR) rs1801394, and methylene
tetrahydrofolate reductase (MTHFR) rs1801133 were examined in 201 children with
ASD and 200 healthy controls from the Han Chinese population. RESULTS Our results
showed no association of all examined SNPs with childhood ASD and its severity.
CONCLUSIONS None of the examined SNPs were a risk factor for the susceptibility
to childhood ASD and severity of the disease in a Han Chinese population.
PMID- 29348399
TI - Insulin-like growth factor 2 is a key mitogen driving liver repopulation in mice.
AB - Hepatocyte transplantation holds great promise as an alternative to orthotopic
organ transplantation in the treatment of liver diseases. However, obtaining
clinically meaningful levels of liver repopulation has not been achieved because
the mechanisms regulating hepatocyte proliferation in recipient livers have not
yet been well characterized. In the mouse model of Hereditary Tyrosinemia Type I,
the fumarylacetoacetate hydrolase-deficient (Fah-/-) mouse, we found gradually
increasing expression level of insulin-like growth factor 2 (IGF2) in the
hepatocytes of host livers. Similarly, high levels of IGF2 were found in the
livers of patients with deficient FAH activity. Recombinant IGF2 directly
promotes proliferation of primary hepatocytes in vitro. Inhibition on IGF2
expression through the interruption of PI3K/Akt and MAPK pathways significantly
reduced the level of liver repopulation in Fah-/- mice. Interestingly, treatment
with IGF2 before hepatocyte transplantation generally improved the amount of
liver repopulation seen in various mice models of liver injury. Altogether, these
findings underscore the underlying mechanisms of therapeutic liver repopulation
in Fah-/- mice, and indicate that IGF2 is a potential hepatocyte mitogen for
liver cell transplantation therapies.
PMID- 29348400
TI - Monoglyceride lipase gene knockout in mice leads to increased incidence of lung
adenocarcinoma.
AB - Monoglyceride lipase (MGL) is a recently discovered cancer-related protein. The
role of MGL in tumorigenesis remains to be fully elucidated. We have previously
shown that MGL expression was reduced or absent in multiple human malignancies,
and overexpression of MGL inhibited cancer cell growth. Here, we have generated
the MGL knockout mice to further investigate the role of MGL in tumorigenesis in
vivo. Our results indicate that MGL-deficient (MGL+/-, MGL-/-) mice exhibited a
higher incidence of neoplasia in multiple organs, including the lung, spleen,
liver and lymphoid tissues. Interestingly, lung neoplasms were the most common
neoplastic changes in the MGL-deficient mice. Importantly, MGL-deficient animals
developed premalignant high-grade dysplasia and adenocarcinomas in their lungs.
Investigation of the MGL expression status in lung cancer specimens from patients
also revealed that MGL expression was significantly reduced in the majority of
primary human lung cancers when compared to corresponding matched normal tissues.
Furthermore, mouse embryonic fibroblasts (MEFs) from MGL-deficient animals showed
characteristics of cellular transformation including increased cell
proliferation, foci formation and anchorage-independent growth. Our results also
indicate that MGL deficiency was associated with activation of EGFR and ERK. In
addition, pro-inflammatory molecules COX-2 and TNF-alpha were also activated in
the MGL-deficient lung tissues. Thus, our results provide new insights into the
novel role of MGL as an important negative regulator of EGFR, COX-2 and TNF
alpha. Accordingly, EGFR and COX-2/TNF-alpha activation/induction is expected to
play important roles in MGL deficiency-driven lung tumors. Collectively, our
results implicate the tumor suppressive role of MGL in preventing tumor
development in vivo, particularly in context to the lung cancer, and highlight
its role as a potential tumor suppressor.
PMID- 29348401
TI - Three-dimensional bicontinuous nanoporous materials by vapor phase dealloying.
AB - Three-dimensional bicontinuous open (3DBO) nanoporosity has been recognized as an
important nanoarchitecture for catalysis, sensing, and energy storage.
Dealloying, i.e., selectively removing a component from an alloy, is an efficient
way to fabricate nanoporous materials. However, current electrochemical and
liquid-metal dealloying methods can only be applied to a limited number of alloys
and usually require an etching process with chemical waste. Here, we report a
green and universal approach, vapor-phase dealloying, to fabricate nanoporous
materials by utilizing the vapor pressure difference between constituent elements
in an alloy to selectively remove a component with a high partial vapor pressure
for 3DBO nanoporosity. We demonstrate that extensive elements, regardless of
chemical activity, can be fabricated as nanoporous materials with tunable pore
sizes. Importantly, the evaporated components can be fully recovered. This
environmentally friendly dealloying method paves a way to fabricate 3DBO
nanoporous materials for a wide range of structural and functional applications.
PMID- 29348402
TI - Self-generated surface magnetic fields inhibit laser-driven sheath acceleration
of high-energy protons.
AB - High-intensity lasers interacting with solid foils produce copious numbers of
relativistic electrons, which in turn create strong sheath electric fields around
the target. The proton beams accelerated in such fields have remarkable
properties, enabling ultrafast radiography of plasma phenomena or isochoric
heating of dense materials. In view of longer-term multidisciplinary purposes
(e.g., spallation neutron sources or cancer therapy), the current challenge is to
achieve proton energies well in excess of 100 MeV, which is commonly thought to
be possible by raising the on-target laser intensity. Here we present
experimental and numerical results demonstrating that magnetostatic fields self
generated on the target surface may pose a fundamental limit to sheath-driven ion
acceleration for high enough laser intensities. Those fields can be strong enough
(~105 T at laser intensities ~1021 W cm-2) to magnetize the sheath electrons and
deflect protons off the accelerating region, hence degrading the maximum energy
the latter can acquire.
PMID- 29348403
TI - Ice volume and climate changes from a 6000 year sea-level record in French
Polynesia.
AB - Mid- to late-Holocene sea-level records from low-latitude regions serve as an
important baseline of natural variability in sea level and global ice volume
prior to the Anthropocene. Here, we reconstruct a high-resolution sea-level curve
encompassing the last 6000 years based on a comprehensive study of coral
microatolls, which are sensitive low-tide recorders. Our curve is based on
microatolls from several islands in a single region and comprises a total of 82
sea-level index points. Assuming thermosteric contributions are negligible on
millennial time scales, our results constrain global ice melting to be 1.5-2.5 m
(sea-level equivalent) since ~5500 years before present. The reconstructed curve
includes isolated rapid events of several decimetres within a few centuries, one
of which is most likely related to loss from the Antarctic ice sheet mass around
5000 years before present. In contrast, the occurrence of large and flat
microatolls indicates periods of significant sea-level stability lasting up to
~300 years.
PMID- 29348405
TI - Directional sound beam emission from a configurable compact multi-source system.
AB - We propose to achieve efficient emission of highly directional sound beams from
multiple monopole sources embedded in a subwavelength enclosure. Without the
enclosure, the emitted sound fields have an indistinguishable or omnidirectional
radiation directivity in far fields. The strong directivity formed in the
presence of the enclosure is attributed to interference of sources under
degenerate Mie resonances in the enclosure of anisotropic property. Our numerical
simulations of sound emission from the sources demonstrate the radiation of a
highly directed sound beam of unidirectional or bidirectional patterns, depending
on how the sources are configured inside the enclosure. Our scheme, if achieved,
can solve the challenging problem of poor directivity of a subwavelength sound
system, and can guide beam forming and collimation by miniaturized devices.
PMID- 29348404
TI - Crystal structure of an assembly intermediate of respiratory Complex II.
AB - Flavin is covalently attached to the protein scaffold in ~10% of flavoenzymes.
However, the mechanism of covalent modification is unclear, due in part to
challenges in stabilizing assembly intermediates. Here, we capture the structure
of an assembly intermediate of the Escherichia coli Complex II (quinol:fumarate
reductase (FrdABCD)). The structure contains the E. coli FrdA subunit bound to
covalent FAD and crosslinked with its assembly factor, SdhE. The structure
contains two global conformational changes as compared to prior structures of the
mature protein: the rotation of a domain within the FrdA subunit, and the
destabilization of two large loops of the FrdA subunit, which may create a tunnel
to the active site. We infer a mechanism for covalent flavinylation. As supported
by spectroscopic and kinetic analyses, we suggest that SdhE shifts the
conformational equilibrium of the FrdA active site to disfavor succinate/fumarate
interconversion and enhance covalent flavinylation.
PMID- 29348406
TI - Active State Organization of Spontaneous Behavioral Patterns.
AB - We report the development and validation of a principled analytical approach to
reveal the manner in which diverse mouse home cage behaviors are organized. We
define and automate detection of two mutually-exclusive low-dimensional
spatiotemporal units of behavior: "Active" and "Inactive" States. Analyses of
these features using a large multimodal 16-strain behavioral dataset provide a
series of novel insights into how feeding, drinking, and movement behaviors are
coordinately expressed in Mus Musculus. Moreover, we find that patterns of Active
State expression are exquisitely sensitive to strain, and classical supervised
machine learning incorporating these features provides 99% cross-validated
accuracy in genotyping animals using behavioral data alone. Altogether, these
findings advance understanding of the organization of spontaneous behavior and
provide a high-throughput phenotyping strategy with wide applicability to
behavioral neuroscience and animal models of disease.
PMID- 29348407
TI - Error-related cardiac response as information for visibility judgements.
AB - Interoception provides information about the saliency of external or internal
sensory events and thus may inform perceptual decision-making. Error in
performance is an example of a motivationally significant internal event that
evokes autonomic nervous system response resembling the orienting response: heart
rate deceleration, increased skin conductance response, and pupil dilation. Here,
we investigate whether error-related cardiac activity may serve as a source of
information when making metacognitive judgments in an orientation discrimination
backward masking task. In the first experiment, we found that the heart
accelerates less after an incorrect stimuli discrimination than after a correct
one. Moreover, this difference becomes more pronounced with increasing subjective
visibility of the stimuli. In the second experiment, this accuracy-dependent
pattern of cardiac activity was found only when participants listened to their
own heartbeats, but not someone else's. We propose that decision accuracy coded
in cardiac activity may be fed as a cue to subjective visibility judgments.
PMID- 29348408
TI - NIPBL+/- haploinsufficiency reveals a constellation of transcriptome disruptions
in the pluripotent and cardiac states.
AB - Cornelia de Lange syndrome (CdLS) is a complex disorder with multiple structural
and developmental defects caused by mutations in structural and regulatory
proteins involved in the cohesin complex. NIPBL, a cohesin regulatory protein,
has been identified as a critical protein responsible for the orchestration of
transcriptomic regulatory networks necessary for embryonic development. Mutations
in NIPBL are responsible for the majority of cases of CdLS. Through RNA
sequencing of human induced pluripotent stem cells and in vitro-derived
cardiomyocytes, we identified hundreds of mRNAs, pseudogenes, and non-coding RNAs
with altered expression in NIPBL+/- patient-derived cells. We demonstrate that
NIPBL haploinsufficiency leads to upregulation of gene sets identified in
functions related to nucleosome, chromatin assembly, RNA modification and
downregulation of Wnt signaling, cholesterol biosynthesis and vesicular transport
in iPSC and cardiomyocytes. Mutations in NIPBL result in the dysregulation of
many genes responsible for normal heart development likely resulting in the
variety of structural cardiac defects observed in the CdLS population.
PMID- 29348409
TI - Artificial selection for improved energy efficiency is reaching its limits in
broiler chickens.
AB - Modern broiler chickens are a major animal husbandry success story, both in terms
of efficient resource utilisation and environmental sustainability. However,
continuing artificial selection for both efficiency and rapid growth will be
subject to both biological limits and animal welfare concerns. Using a novel
analytical energy flow modelling approach, we predict how far such selection can
go, given the biological limits of bird energy intake and partitioning of energy.
We find that the biological potential for further improvements in efficiency, and
hence environmental impact reduction, is minimal relative to past progress
already made via artificial selection. An alternative breeding strategy to
produce slower-growing birds to meet new welfare standards increases
environmental burdens, compared to current birds. This unique analytic approach
provides biologically sound guidelines for strategic planning of sustainable
broiler production.
PMID- 29348410
TI - Oxidative stress via inhibition of the mitochondrial electron transport and Nrf-2
mediated anti-oxidative response regulate the cytotoxic activity of plumbagin.
AB - Plumbagin, an anti-cancer agent, is toxic to cells of multiple species. We
investigated if plumbagin targets conserved biochemical processes. Plumbagin
induced DNA damage and apoptosis in cells of diverse mutational background with
comparable potency. A 3-5 fold increase in intracellular oxygen radicals occurred
in response to plumbagin. Neutralization of the reactive oxygen species by N
acetylcysteine blocked apoptosis, indicating a central role for oxidative stress
in plumbagin-mediated cell death. Plumbagin docks in the ubiquinone binding sites
(Q0 and Qi) of mitochondrial complexes I-III, the major sites for oxygen
radicals. Plumbagin decreased oxygen consumption rate, ATP production and optical
redox ratio (NAD(P)H/FAD) indicating interference with electron transport
downstream of mitochondrial Complex II. Oxidative stress induced by plumbagin
triggered an anti-oxidative response via activation of Nrf2. Plumbagin and the
Nrf2 inhibitor, brusatol, synergized to inhibit cell proliferation. These data
indicate that while inhibition of electron transport is the conserved mechanism
responsible for plumbagin's chemotoxicity, activation of Nrf2 is the resulting
anti-oxidative response that allows plumbagin to serve as a chemopreventive
agent. This study provides the basis for designing potent and selective plumbagin
analogs that can be coupled with suitable Nrf2 inhibitors for chemotherapy or
administered as single agents to induce Nrf2-mediated chemoprevention.
PMID- 29348411
TI - In vivo Microscopic Photoacoustic Spectroscopy for Non-Invasive Glucose
Monitoring Invulnerable to Skin Secretion Products.
AB - Photoacoustic spectroscopy has been shown to be a promising tool for non-invasive
blood glucose monitoring. However, the repeatability of such a method is
susceptible to changes in skin condition, which is dependent on hand washing and
drying due to the high absorption of infrared excitation light to the skin
secretion products or water. In this paper, we present a method to meet the
challenges of mid-infrared photoacoustic spectroscopy for non-invasive glucose
monitoring. By obtaining the microscopic spatial information of skin during the
spectroscopy measurement, the skin region where the infrared spectra is
insensitive to skin condition can be locally selected, which enables reliable
prediction of the blood glucose level from the photoacoustic spectroscopy
signals. Our raster-scan imaging showed that the skin condition for in vivo
spectroscopic glucose monitoring had significant inhomogeneities and large
variability in the probing area where the signal was acquired. However, the
selective localization of the probing led to a reduction in the effects of
variability due to the skin secretion product. Looking forward, this technology
has broader applications not only in continuous glucose monitoring for diabetic
patient care, but in forensic science, the diagnosis of malfunctioning sweat
pores, and the discrimination of tumors extracted via biopsy.
PMID- 29348412
TI - Influence of autophagy on acute kidney injury in a murine cecal ligation and
puncture sepsis model.
AB - The role of autophagy in the maintenance of renal homeostasis during sepsis is
not well understood. We therefore aimed to determine the influence of autophagy
on kidney during sepsis using a murine sepsis model, i.e. cecal ligation and
puncture (CLP). In CLP treated animals, the number of autolysosomes observed by
electron microscopy increased over time. The number of autophagosomes in CLP
animals decreased relative sham operated controls at 24 hrs after CLP, indicating
that autophagy flux is already diminishing by that time. Moreover, CLP induced an
increase in LC3-II/LC3-I ratio at 6-8 hrs, demonstrated in western blots, as well
as an increase in GFP-LC3 dots at 6-8 hrs and 24 hrs, using immunofluorescence
and anti-LC3 and LAMP1 antibodies on tissue sections from GFP-LC3 transgenic
mice. LC3-II/LC3-I ratio and the number of co-localized GFP-LC3 dots and LAMP1
signals (GFP LC3 + LAMP1 dots) in CLP mice at 24 hrs were significantly reduced
compared with data obtained at 6-8 hrs. Notably, acceleration of autophagy by
rapamycin resulted in improvement of renal function that was associated with
improvement in the histologic severity of tubular epithelial injury in CLP
treated animals. Autophagy in the kidney was significantly slowed in the kidney
during the acute phase of sepsis; nonetheless, autophagy in kidney appears to
play a protective role against sepsis.
PMID- 29348413
TI - Synthesis of Luminescent Carbon Dots with Ultrahigh Quantum Yield and Inherent
Folate Receptor-Positive Cancer Cell Targetability.
AB - Carbon dots (CDs) have a wide range of applications in chemical, physical and
biomedical research fields. We are particularly interested in the use of CDs as
fluorescence nanomaterials for targeted tumor cell imaging. One of the important
aspects of success is to enhance the fluorescence quantum yields (QY) of CDs as
well as increase their targetability to tumor cells. However, most of the
reported CDs are limited by relative low QY. In the current study, for the first
time, one-step synthesis of highly luminescent CDs by using folic acid (FA) as
single precursor was obtained in natural water through hydrothermal method. The
as-prepared CDs exhibited QY as high as 94.5% in water, which is even higher than
most of organic fluorescent dyes. The obtained CDs showed excellent
photoluminescent activity, high photostability and favorable biocompatibility.
The FA residuals in CDs led to extraordinary targetability to cancer cells and
promoted folate receptor-mediated cellular uptake successfully, which holds a
great potential in biological and bioimaging studies.
PMID- 29348414
TI - MicroRNA-146a-5p attenuates irradiation-induced and LPS-induced hepatic stellate
cell activation and hepatocyte apoptosis through inhibition of TLR4 pathway.
AB - Elevated toll-like receptor 4 (TLR4) expression is associated with a high risk of
radiation-induced liver disease (RILD). MicroRNA (miR)-146a-5p is a key regulator
of lipopolysaccharide (LPS)/TLR4 signaling, but its role in modulation of RILD
remains unclear. Here, we found that irradiation and LPS stimulation induced TLR4
and miR-146a-5p expression in the human hepatic stellate cell (HSC) line LX2.
Ectopic expression of miR-146a-5p in LX2 inhibited irradiation-induced and LPS
induced pro-inflammatory cytokine secretion and cell proliferation, and promoted
cell apoptosis by down-regulating the expression levels of TLR4, interleukin-1
receptor associated kinase 1 (IRAK1), tumor necrosis factor receptor associated
factor 6 (TRAF6) and phosphorylation of nuclear factor-kappa B. In addition, the
culture medium from the irradiated and LPS-stimulated HSCs transfected with miR
146a-5p significantly attenuated apoptosis in irradiated hepatocytes.
Overexpression of miR-146a-5p reduced alpha-smooth muscle actin production in
irradiated and LPS-stimulated LX2 cells, which was associated with inhibition of
TRAF6-mediated JNK and Smad2 phosphorylation. Knockdown of TRAF6 or IRAK1
mimicked the effects of miR-146a-5p on HSC function. Furthermore, miR-146a-5p
treatment alleviated irradiation-induced and endotoxin-induced hepatic
inflammatory response and fibrogenesis in mice through inhibition of the TLR4
signaling pathway. Collectively, this study reveals the anti-pro-inflammatory and
anti-fibrotic effects of miR-146a-5p on liver injury, and suggests a potential
application of miR-146a-5p in the therapeutic prevention of RILD.
PMID- 29348415
TI - Trends in Fetal Growth Between 2000 to 2014 in Singleton Live Births from Israel.
AB - Trends in birthweight and abnormal fetal growth, namely term low birthweight
(LBW), macrosomia, small-for-gestational age (SGA) and large-for-gestational age
(LGA), are important indicators of changes in the health of populations. We
performed this epidemiological study to evaluate these trends among 2,039,415
singleton live births from Israel over a period of 15 years. Birth certificate
data was obtained from the Ministry of Health. Multivariable linear and logistic
regression models were used to evaluate crude and adjusted estimates compared to
the baseline of 2000 and polynomial trends. During the study period we observed a
significant decrease in the rates of infants born SGA and LGA (10.7% to 9.2%,
10.2% to 9.6% respectively). After adjustment, based on the imputed data set,
term mean birthweight increased by 6.0 grams (95% CI: 2.9, 9.1), and term LBW
odds decreased by 19% in 2014 compared to 2000 (adj ORs: 0.81; 95% CI: 0.77,
0.85). Significant decreases were also observed for adjusted SGA, LGA and
macrosomia rates. The decrease in abnormal fetal growth rates were not entirely
explained by changes in sociodemographic characteristics or gestational age and
may imply real improvement in child intrauterine growth in Israel during the last
15 years, especially in the Jewish population.
PMID- 29348416
TI - Magneto Acoustic Spin Hall Oscillators.
AB - This paper introduces a novel oscillator that combines the tunability of spin
Hall-driven nano oscillators with the high quality factor (Q) of high overtone
bulk acoustic wave resonators (HBAR), integrating both reference and tunable
oscillators on the same chip with CMOS. In such magneto acoustic spin Hall (MASH)
oscillators, voltage oscillations across the magnetic tunnel junction (MTJ) that
arise from a spin-orbit torque (SOT) are shaped by the transmission response of
the HBAR that acts as a multiple peak-bandpass filter and a delay element due to
its large time constant, providing delayed feedback. The filtered voltage
oscillations can be fed back to the MTJ via (a) strain, (b) current, or (c)
magnetic field. We develop a SPICE-based circuit model by combining
experimentally benchmarked models including the stochastic Landau-Lifshitz
Gilbert (sLLG) equation for magnetization dynamics and the Butterworth Van Dyke
(BVD) circuit for the HBAR. Using the self-consistent model, we project up to
~50X enhancement in the oscillator linewidth with Q reaching up to 52825 at 3
GHz, while preserving the tunability by locking the STNO to the nearest high Q
peak of the HBAR. We expect that our results will inspire MEMS-based solutions to
spintronic devices by combining attractive features of both fields for a variety
of applications.
PMID- 29348417
TI - Identification of a membrane-less compartment regulating invadosome function and
motility.
AB - Depletion of liprin-alpha1, ERC1 or LL5 scaffolds inhibits extracellular matrix
degradation by invasive cells. These proteins co-accumulate near invadosomes in
NIH-Src cells, identifying a novel invadosome-associated compartment distinct
from the core and adhesion ring of invadosomes. Depletion of either protein
perturbs the organization of invadosomes without influencing the recruitment of
MT1-MMP metalloprotease. Liprin-alpha1 is not required for de novo formation of
invadosomes after their disassembly by microtubules and Src inhibitors, while its
depletion inhibits invadosome motility, thus affecting matrix degradation.
Fluorescence recovery after photobleaching shows that the invadosome-associated
compartment is dynamic, while correlative light immunoelectron microscopy
identifies bona fide membrane-free invadosome-associated regions enriched in
liprin-alpha1, which is virtually excluded from the invadosome core. The results
indicate that liprin-alpha1, LL5 and ERC1 define a novel dynamic membrane-less
compartment that regulates matrix degradation by affecting invadosome motility.
PMID- 29348418
TI - A Novel Modeling in Mathematical Biology for Classification of Signal Peptides.
AB - The molecular structure of macromolecules in living cells is ambiguous unless we
classify them in a scientific manner. Signal peptides are of vital importance in
determining the behavior of newly formed proteins towards their destined path in
cellular and extracellular location in both eukaryotes and prokaryotes. In the
present research work, a novel method is offered to foreknow the behavior of
signal peptides and determine their cleavage site. The proposed model employs
neural networks using isolated sets of prokaryote and eukaryote primary
sequences. Protein sequences are classified as secretory or non-secretory in
order to investigate secretory proteins and their signal peptides. In comparison
with the previous prediction tools, the proposed algorithm is more rigorous, well
organized, significantly appropriate and highly accurate for the examination of
signal peptides even in extensive collection of protein sequences.
PMID- 29348419
TI - Dysbindin links presynaptic proteasome function to homeostatic recruitment of low
release probability vesicles.
AB - Here we explore the relationship between presynaptic homeostatic plasticity and
proteasome function at the Drosophila neuromuscular junction. First, we
demonstrate that the induction of homeostatic plasticity is blocked after
presynaptic proteasome perturbation. Proteasome inhibition potentiates release
under baseline conditions but not during homeostatic plasticity, suggesting that
proteasomal degradation and homeostatic plasticity modulate a common pool of
vesicles. The vesicles that are regulated by proteasome function and recruited
during homeostatic plasticity are highly EGTA sensitive, implying looser Ca2+
influx-release coupling. Similar to homeostatic plasticity, proteasome
perturbation enhances presynaptic Ca2+ influx, readily-releasable vesicle pool
size, and does not potentiate release after loss of specific homeostatic
plasticity genes, including the schizophrenia-susceptibility gene dysbindin.
Finally, we provide genetic evidence that Dysbindin levels regulate the access to
EGTA-sensitive vesicles. Together, our data suggest that presynaptic protein
degradation opposes the release of low-release probability vesicles that are
potentiated during homeostatic plasticity and whose access is controlled by
dysbindin.
PMID- 29348420
TI - Gender-related differences in heart failure with preserved ejection fraction.
AB - Heart failure with preserved ejection fraction (HFpEF) affects more women than
men, suggesting gender to play a major role in disease evolution. However,
studies investigating gender differences in HFpEF are limited. In the present
study we aimed to describe gender differences in a well-characterized HFpEF
cohort. Consecutive HFpEF patients underwent invasive hemodynamic assessment,
cardiac magnetic resonance imaging and exercise testing. Study endpoints were:
cardiac death, a combined endpoint of HF hospitalization or cardiac death and all
cause death. 260 HFpEF patients were prospectively enrolled. Men were more
compromised with regard to exercise capacity and had significantly more co
morbidities. Men had more pronounced pulmonary vascular disease with higher
diastolic pressure gradients and a lower right ventricular EF. During follow-up,
9.2% experienced cardiac death, 33.5% the combined endpoint and 17.3% all-cause
death. Male gender was independently associated with cardiac death, but neither
with the combined endpoint nor with all-cause mortality. We detected clear gender
differences in HFpEF patients. Cardiac death was more common among men, but not
all-cause death. While men are more prone to develop a right heart phenotype and
die from HFpEF, women are more likely to die with HFpEF.
PMID- 29348421
TI - Patients over 40 years old with precursor T-cell lymphoblastic lymphoma have
different prognostic factors comparing to the youngers.
AB - This study aimed to analyze the clinical characteristics and prognostic factors
of patients, divided into over 40-year-old group or not, with precursor T-cell
lymphoblastic lymphoma (Pre-T-LBL). Based on the retrospective analysis of the
clinical data of 59 patients with Pre-T-LBL during the period from December 2010
to December 2015, albumin level, anemia, pleural or pericardial effusion,
protocol, therapy response, mediastinal mass, lactate dehydrogenase (LDH), and
international prognostic index (IPI) or age-adjusted international prognostic
index (aaIPI) were summarized. For patients aged <40 years, factors correlating
with poor progression-free survival (PFS) were pleural or pericardial effusion,
regimen, albumin level and therapy response. Pleural or pericardial effusion,
aaIPI score, regimen, LDH increased, albumin level, therapy response and
mediastinal mass were all related with poor overall survival (OS). In the
patients aged >=40 years, only anemia associated with PFS. However, anemia,
involvement of bone marrow and therapeutic response were all related with poor
OS. In conclusion, the patients with Pre-T-LBL are characterized by a low
incidence and bad prognosis. Different prognostic factors can be discovered for
patients over 40-year-old with Pre-T-LBL comparing to the youngers. New
prognostic evaluation factors should be explored for patients >=40 years old.
PMID- 29348422
TI - Individuals with depressive tendencies experience difficulty in forgetting
negative material: two mechanisms revealed by ERP data in the directed forgetting
paradigm.
AB - Although previous studies have shown that individuals with depressive tendencies
have deficits in forgetting negative material, the detailed underlying neural
mechanisms have not been elucidated. This study examined the intentional
forgetting of negative and neutral material in individuals with depressive
tendencies in two phases. In the study phase, the participants performed a
directed forgetting task, where a total of 320 words were presented to them, each
followed by an instructive cue to forget or remember the previously presented
word. Subsequently, in the memory recognition test phase, the participants
completed the "old or new discrimination task". The results indicated that
individuals with depressive tendencies had difficulties suppressing the memory
encoding of negative words, while the suppression of memory encoding of neutral
words was relatively intact. Moreover, individuals with depressive tendencies
displayed enhanced word-evoked P2 and late positive potential for negative items,
as well as enhanced cue-evoked P1 and N2 for the negative items that were
required to be forgotten, as compared to individuals without depressive
tendencies. Based on these results, we propose two mechanisms that may contribute
to the failure of forgetting negative material in mild depression: (1)
inefficient memory suppression and early selective attention, and (2) excessive
preliminary processing.
PMID- 29348423
TI - A tissue-mimetic nano-fibrillar hybrid injectable hydrogel for potential soft
tissue engineering applications.
AB - While collagen type I (Col-I) is commonly used as a structural component of
biomaterials, collagen type III (Col-III), another fibril forming collagen
ubiquitous in many soft tissues, has not previously been used. In the present
study, the novel concept of an injectable hydrogel with semi-interpenetrating
polymeric networks of heterotypic collagen fibrils, with tissue-specific Col-III
to Col-I ratios, in a glycol-chitosan matrix was investigated. Col-III was
introduced as a component of the novel hydrogel, inspired by its co-presence with
Col-I in many soft tissues, its influence on the Col-I fibrillogenesis in terms
of diameter and mechanics, and its established role in regulating scar formation.
The hydrogel has a nano-fibrillar porous structure, and is mechanically stable
under continuous dynamic stimulation. It was found to provide a longer half-life
of about 35 days than similar hyaluronic acid-based hydrogels, and to support
cell implantation in terms of viability, metabolic activity, adhesion and
migration. The specific case of pure Col-III fibrils in a glycol-chitosan matrix
was investigated. The proposed hydrogels meet many essential requirements for
soft tissue engineering applications, particularly for mechanically challenged
tissues such as vocal folds and heart valves.
PMID- 29348424
TI - Intraocular inflammatory cytokines in patients with neovascular age-related
macular degeneration before and after initiation of intravitreal injection of
anti-VEGF inhibitor.
AB - Age-related macular degeneration (AMD) is a cause of blindness in people older
than 50 years. Accumulating evidence indicates the involvement of systemic and
local inflammation in the pathogenesis and progression of AMD. Aflibercept is an
anti-vascular endothelial growth factor (VEGF) inhibitor, and intravitreal
injection of aflibercept (IVA) is the approved treatments of neovascular AMD
(nAMD), but the effect on inflammatory response remains unclear. The aim of our
study was to investigate the profiles of inflammatory cytokines in the aqueous
humor of nAMD patients before and after initiation of IVA. In nAMD patients, IP
10 level was significantly higher and IL-6 level was significantly lower compared
with those of cataract patients as controls. Logistic regression analysis
identified IP-10 as a positive factor and IL-6 a negative factor associated with
the pathogenesis of nAMD. In addition, IP-10 level correlated positively with the
mean thickness of macula in the central 1-mm diameter circle. After initiation of
IVA, IP-10 level was further elevated, and correlated negatively with VEGF level.
These data suggest that IP-10 plays a critical role as an antiangiogenic factor
and at the same time an inflammatory factor in the pathogenesis and
pathophysiology of nAMD eyes at onset and after IVA initiation.
PMID- 29348425
TI - Serum uric acid levels in patients with amyotrophic lateral sclerosis: a meta
analysis.
AB - The pathogenic mechanism of ALS remains unclear. However, increasing evidence has
indicated that uric acid (UA) may play a protective role in the pathogenesis of
ALS. The aim of this study was to evaluate the association between serum UA
levels and ALS. A comprehensive literature search in PubMed, Embase, Web of
Science, and Cochrane Library was conducted up to 31st August, 2017, using
keywords. A random-effects model or fixed-effects model was used to calculate the
pooled estimate according to the inter-group heterogeneity. Finally, we
indentified 8 case-control and 3 cohort studies. The results indicated that
patients with ALS had significant decreased levels of serum UA compared to
healthy controls (standardized mean difference (SMD) = -0.72, 95% CI [-0.98,
0.46], P < 0.001). Increased serum UA levels were associated with lower all-cause
mortality risk among ALS patients (risk ratio (RR) = 0.70, 95% CI [0.57, 0.87], P
= 0.001). To summarize, there is an inverse association between serum UA levels
and risk of death among ALS patients. Randomized controlled trials with high
quality are required to elucidate the role of UA on ALS.
PMID- 29348426
TI - One protein, different cell fate: the differential outcome of depleting GRP75
during oxidative stress in neurons.
PMID- 29348427
TI - Multi-stage volcanic island flank collapses with coeval explosive caldera-forming
eruptions.
AB - Volcanic flank collapses and explosive eruptions are among the largest and most
destructive processes on Earth. Events at Mount St. Helens in May 1980
demonstrated how a relatively small (<5 km3) flank collapse on a terrestrial
volcano could immediately precede a devastating eruption. The lateral collapse of
volcanic island flanks, such as in the Canary Islands, can be far larger (>300
km3), but can also occur in complex multiple stages. Here, we show that
multistage retrogressive landslides on Tenerife triggered explosive caldera
forming eruptions, including the Diego Hernandez, Guajara and Ucanca caldera
eruptions. Geochemical analyses were performed on volcanic glasses recovered from
marine sedimentary deposits, called turbidites, associated with each individual
stage of each multistage landslide. These analyses indicate only the lattermost
stages of subaerial flank failure contain materials originating from respective
coeval explosive eruption, suggesting that initial more voluminous submarine
stages of multi-stage flank collapse induce these aforementioned explosive
eruption. Furthermore, there are extended time lags identified between the
individual stages of multi-stage collapse, and thus an extended time lag between
the initial submarine stages of failure and the onset of subsequent explosive
eruption. This time lag succeeding landslide-generated static decompression has
implications for the response of magmatic systems to un-roofing and poses a
significant implication for ocean island volcanism and civil emergency planning.
PMID- 29348428
TI - Evaluation of quantitative parameters for distinguishing pheochromocytoma from
other adrenal tumors.
AB - Adrenal tumors are increasingly found incidentally during imaging examinations.
It is important to distinguish pheochromocytomas from other adrenal tumors
because of the risk of hypertensive crisis. Although catecholamines and their
metabolites are generally used to diagnose pheochromocytoma, false-positive test
results are common. An effective screening method to distinguish pheochromocytoma
from adrenal incidentalomas is needed. We analyzed 297 consecutive patients with
adrenal incidentalomas. Our findings included 162 non-functioning tumors, 47
aldosterone-producing adenomas, 26 metastases, 22 cases of subclinical Cushing's
syndrome, 21 pheochromocytomas, 12 cases of Cushing's syndrome, and 7
adrenocortical cancers. We checked quantitative parameters such as age, blood,
and urine catecholamines and their metabolites, neuron-specific enolase, size and
computed tomography (CT) attenuation values. Among catecholamine-related
parameters, the sum of urine metanephrine and normetanephrine (urineMNM) levels
produced the highest area under the receiver operating characteristic curve
regarding discrimination of pheochromocytoma from other lesions. Size and CT
attenuation values also differed significantly. However, size was correlated with
catecholamine levels. CT attenuation was not correlated with other factors. The
optimal thresholds were 19 Hounsfield units (HU) for CT attenuation (sensitivity,
100%; specificity, 60%) and 0.43 mg/24 h for urineMNM (sensitivity, 89%;
specificity, 96%). No pheochromocytomas were evident when CT attenuation values
were under 19 HU. Even in adrenal tumors with CT attenuation values >= 19 HU,
when urineMNM was < 0.43 mg/24 h, the frequency of pheochromocytoma was only
4.3%, when urineMNM was >= 0.43 mg/24 h, the frequency of pheochromocytoma was
93% and when urineMNM was > 0.77 mg/24 h the frequency of pheochromocytoma was
100%. CT attenuation value and urineMNM represented the most useful combination
for diagnosis of pheochromocytoma.
PMID- 29348429
TI - Structural basis of trans-synaptic interactions between PTPdelta and SALMs for
inducing synapse formation.
AB - Synapse formation is triggered by trans-synaptic interactions of cell adhesion
molecules, termed synaptic organizers. Three members of type-II receptor protein
tyrosine phosphatases (classified as type-IIa RPTPs; PTPdelta, PTPsigma and LAR)
are known as presynaptic organizers. Synaptic adhesion-like molecules (SALMs)
have recently emerged as a family of postsynaptic organizers. Although all five
SALM isoforms can bind to the type-IIa RPTPs, only SALM3 and SALM5 reportedly
have synaptogenic activities depending on their binding. Here, we report the
crystal structures of apo-SALM5, and PTPdelta-SALM2 and PTPdelta-SALM5 complexes.
The leucine-rich repeat (LRR) domains of SALMs interact with the second
immunoglobulin-like (Ig) domain of PTPdelta, whereas the Ig domains of SALMs
interact with both the second and third Ig domains of PTPdelta. Unexpectedly, the
structures exhibit the LRR-mediated 2:2 complex. Our synaptogenic co-culture
assay using site-directed SALM5 mutants demonstrates that presynaptic
differentiation induced by PTPdelta-SALM5 requires the dimeric property of SALM5.
PMID- 29348430
TI - Rotator side chains trigger cooperative transition for shape and function memory
effect in organic semiconductors.
AB - Martensitic transition is a solid-state phase transition involving cooperative
movement of atoms, mostly studied in metallurgy. The main characteristics are low
transition barrier, ultrafast kinetics, and structural reversibility. They are
rarely observed in molecular crystals, and hence the origin and mechanism are
largely unexplored. Here we report the discovery of martensitic transition in
single crystals of two different organic semiconductors. In situ microscopy,
single-crystal X-ray diffraction, Raman and nuclear magnetic resonance
spectroscopy, and molecular simulations combined indicate that the rotating bulky
side chains trigger cooperative transition. Cooperativity enables shape memory
effect in single crystals and function memory effect in thin film transistors. We
establish a molecular design rule to trigger martensitic transition in organic
semiconductors, showing promise for designing next-generation smart
multifunctional materials.
PMID- 29348431
TI - A synthetic combinatorial approach to disabling deviant Hedgehog signaling.
AB - Mutations in components of the Hedgehog (HH) signal transduction pathway are
found in the majority of basal cell carcinoma (BCC) and medulloblastoma
incidents. Cancerous cells with intrinsic or acquired resistance to antagonists
targeting the seven transmembrane effector Smoothened (SMO) frequently invoke
alternative mechanisms for maintaining deviant activity of the GLI DNA binding
proteins. Here we introduce a chemical agent that simultaneously achieves
inhibition of SMO and GLI activity by direct targeting of the SMO heptahelical
domain and the GLI-modifying enzymes belonging to the histone deacetylase (HDAC)
family. We demonstrate a small molecule SMO-HDAC antagonist (IHR-SAHA) retains
inhibitory activity for GLI transcription induced by SMO-dependent and
independent mechanisms frequently associated with cancer biogenesis. Synthetic
combinatorial therapeutic agents such as IHR-SAHA that a priori disable cancer
drivers and anticipated mechanisms of drug resistance could extend the duration
of disease remission, and provide an alternative clinical development path for
realizing combinatorial therapy modalities.
PMID- 29348433
TI - Speciation of common Gram-negative pathogens using a highly multiplexed high
resolution melt curve assay.
AB - The identification of the bacterial species responsible for an infection remains
an important step for the selection of antimicrobial therapy. Gram-negative
bacteria are an important source of hospital and community acquired infections
and frequently antimicrobial resistant. Speciation of bacteria is typically
carried out by biochemical profiling of organisms isolated from clinical
specimens, which is time consuming and delays the initiation of tailored
treatment. Whilst molecular methods such as PCR have been used, they often
struggle with the challenge of detecting and discriminating a wide range of
targets. High resolution melt analysis is an end-point qPCR detection method that
provides greater multiplexing capability than probe based methods. Here we report
the design of a high resolution melt analysis assay for the identification of six
common Gram-negative pathogens; Escherichia coli, Klebsiella pneumoniae,
Klebsiella oxytoca, Pseudomonas aeruginosa, Salmonella Sp, and Acinetobacter
baumannii, and a generic Gram-negative specific 16S rRNA control. The assay was
evaluated using a well characterised collection of 113 clinically isolated Gram
negative bacteria. The agreement between the HRM assay and the reference test of
PCR and sequencing was 98.2% (Kappa 0.96); the overall sensitivity and
specificity of the assay was 97.1% (95% CI: 90.1-99.7%) and 100% (95% CI: 91.78
100%) respectively.
PMID- 29348432
TI - Genome-wide association study of self-reported food reactions in Japanese
identifies shrimp and peach specific loci in the HLA-DR/DQ gene region.
AB - Food allergy is an increasingly important health problem in the world. Several
genome-wide association studies (GWAS) focused on European ancestry samples have
identified food allergy-specific loci in the HLA class II region. We conducted
GWAS of self-reported reactivity with common foods using the data from 11011
Japanese women and identified shrimp and peach allergy-specific loci in the HLA
DR/DQ gene region tagged by rs74995702 (P = 6.30 * 10-17, OR = 1.91) and
rs28359884 (P = 2.3 * 10-12, OR = 1.80), respectively. After HLA imputation using
a Japanese population-specific reference, the most strongly associated haplotype
was HLA-DRB1*04:05-HLA-DQB1*04:01 for shrimp allergy (P = 3.92 * 10-19, OR =
1.99) and HLA-DRB1*09:01-HLA-DQB1*03:03 for peach allergy (P = 1.15 * 10-7, OR =
1.68). Additionally, both allergies' associated variants were eQTLs for several
HLA genes, with HLA-DQA2 the single eQTL gene shared between the two traits. Our
study suggests that allergy to certain foods may be related to genetic
differences that tag both HLA alleles having particular epitope binding
specificities as well as variants modulating expression of particular HLA genes.
Investigating this further could increase our understanding of food allergy
aetiology and potentially lead to better therapeutic strategies for allergen
immunotherapies.
PMID- 29348436
TI - High-throughput analysis using non-depletive SPME: challenges and applications to
the determination of free and total concentrations in small sample volumes.
AB - In vitro high-throughput non-depletive quantitation of chemicals in biofluids is
of growing interest in many areas. Some of the challenges facing researchers
include the limited volume of biofluids, rapid and high-throughput sampling
requirements, and the lack of reliable methods. Coupled to the above, growing
interest in the monitoring of kinetics and dynamics of miniaturized biosystems
has spurred the demand for development of novel and revolutionary methodologies
for analysis of biofluids. The applicability of solid-phase microextraction
(SPME) is investigated as a potential technology to fulfill the aforementioned
requirements. As analytes with sufficient diversity in their physicochemical
features, nicotine, N,N-Diethyl-meta-toluamide, and diclofenac were selected as
test compounds for the study. The objective was to develop methodologies that
would allow repeated non-depletive sampling from 96-well plates, using 100 uL of
sample. Initially, thin film-SPME was investigated. Results revealed substantial
depletion and consequent disruption in the system. Therefore, new ultra-thin
coated fibers were developed. The applicability of this device to the described
sampling scenario was tested by determining the protein binding of the analytes.
Results showed good agreement with rapid equilibrium dialysis. The presented
method allows high-throughput analysis using small volumes, enabling fast
reliable free and total concentration determinations without disruption of system
equilibrium.
PMID- 29348435
TI - Macrophage sensing of single-walled carbon nanotubes via Toll-like receptors.
AB - Carbon-based nanomaterials including carbon nanotubes (CNTs) have been shown to
trigger inflammation. However, how these materials are 'sensed' by immune cells
is not known. Here we compared the effects of two carbon-based nanomaterials,
single-walled CNTs (SWCNTs) and graphene oxide (GO), on primary human monocyte
derived macrophages. Genome-wide transcriptomics assessment was performed at sub
cytotoxic doses. Pathway analysis of the microarray data revealed pronounced
effects on chemokine-encoding genes in macrophages exposed to SWCNTs, but not in
response to GO, and these results were validated by multiplex array-based
cytokine and chemokine profiling. Conditioned medium from SWCNT-exposed cells
acted as a chemoattractant for dendritic cells. Chemokine secretion was reduced
upon inhibition of NF-kappaB, as predicted by upstream regulator analysis of the
transcriptomics data, and Toll-like receptors (TLRs) and their adaptor molecule,
MyD88 were shown to be important for CCL5 secretion. Moreover, a specific role
for TLR2/4 was confirmed by using reporter cell lines. Computational studies to
elucidate how SWCNTs may interact with TLR4 in the absence of a protein corona
suggested that binding is guided mainly by hydrophobic interactions. Taken
together, these results imply that CNTs may be 'sensed' as pathogens by immune
cells.
PMID- 29348438
TI - Procalcitonin Guiding Antimicrobial Therapy Duration in Febrile Cancer Patients
with Documented Infection or Neutropenia.
AB - In this analysis, we identified febrile cancer patients with documented
infections or neutropenia, whose procalcitonin levels are low at baseline or
decrease on antibiotics. These patients had similar outcomes in terms of
mortality and relapse of infection regardless of the duration of antimicrobial
therapy (less or more than 7 days).
PMID- 29348439
TI - Dual suppression of inner and outer mitochondrial membrane functions augments
apoptotic responses to oncogenic MAPK inhibition.
AB - Mitogen-activated protein kinase (MAPK) pathway inhibitors show promise in
treating melanoma, but are unsuccessful in achieving long-term remission.
Concordant with clinical data, BRAFV600E melanoma cells eliminate glycolysis upon
inhibition of BRAFV600E or MEK with the targeted therapies Vemurafenib or
Trametinib, respectively. Consequently, exposure to these therapies reprograms
cellular metabolism to increase mitochondrial respiration and restrain cell death
commitment. As the inner mitochondrial membrane (IMM) is sub-organellar site of
oxidative phosphorylation (OXPHOS), and the outer mitochondrial membrane (OMM) is
the major site of anti-apoptotic BCL-2 protein function, we hypothesized that
suppressing these critical mitochondrial membrane functions would be a rational
approach to maximize the pro-apoptotic effect of MAPK inhibition. Here, we
demonstrate that disruption of OXPHOS with the mitochondria-specific protonophore
BAM15 promotes the mitochondrial pathway of apoptosis only when oncogenic MAPK
signaling is inhibited. Based on RNA-sequencing analyses of nevi and primary
melanoma samples, increased pro-apoptotic BCL-2 family expression positively
correlates with high-risk disease suggesting a highly active anti-apoptotic BCL-2
protein repertoire likely contributes to worse outcome. Indeed, combined
inhibition of the anti-apoptotic BCL-2 repertoire with BH3-mimetics, OXPHOS, and
oncogenic MAPK signaling induces fulminant apoptosis and eliminates clonogenic
survival. Altogether, these data suggest that dual suppression of IMM and OMM
functions may unleash the normally inadequate pro-apoptotic effects of oncogenic
MAPK inhibition to eradicate cancer cells, thus preventing the development of
resistant disease, and ultimately, supporting long-term remission.
PMID- 29348437
TI - First experimental proof of Proton Boron Capture Therapy (PBCT) to enhance
protontherapy effectiveness.
AB - Protontherapy is hadrontherapy's fastest-growing modality and a pillar in the
battle against cancer. Hadrontherapy's superiority lies in its inverted depth
dose profile, hence tumour-confined irradiation. Protons, however, lack distinct
radiobiological advantages over photons or electrons. Higher LET (Linear Energy
Transfer) 12C-ions can overcome cancer radioresistance: DNA lesion complexity
increases with LET, resulting in efficient cell killing, i.e. higher Relative
Biological Effectiveness (RBE). However, economic and radiobiological issues
hamper 12C-ion clinical amenability. Thus, enhancing proton RBE is desirable. To
this end, we exploited the p + 11B -> 3alpha reaction to generate high-LET alpha
particles with a clinical proton beam. To maximize the reaction rate, we used
sodium borocaptate (BSH) with natural boron content. Boron-Neutron Capture
Therapy (BNCT) uses 10B-enriched BSH for neutron irradiation-triggered alpha
particles. We recorded significantly increased cellular lethality and chromosome
aberration complexity. A strategy combining protontherapy's ballistic precision
with the higher RBE promised by BNCT and 12C-ion therapy is thus demonstrated.
PMID- 29348440
TI - Neural predictors of cognitive improvement by multi-strategic memory training
based on metamemory in older adults with subjective memory complaints.
AB - Previous studies have indicated that memory training may help older people
improve cognition. However, evidence regarding who will benefit from such memory
trainings has not been fully discovered yet. Understanding the clinical and
neural inter-individual differences for predicting cognitive improvement is
important for maximizing the training efficacy of memory-training programs. The
purpose of this study was to find the individual characteristics and brain
morphological characteristics that predict cognitive improvement after a multi
strategic memory training based on metamemory concept. Among a total of 49 older
adults, 39 participated in the memory-training program and 10 did not. All of
them underwent brain MRIs at the entry of the training and received the
neuropsychological tests twice, before and after the training. Stepwise
regression analysis showed that lower years of education predicted cognitive
improvement in the training group. In MRI, thinner cortices of precuneus, cuneus
and posterior cingulate gyrus and higher white matter anisotropy of the splenium
of corpus callosum predicted cognitive improvement in the training group. Old
age, lower education level and individual differences in cortical thickness and
white matter microstructure of the episodic memory network may predict outcomes
following multi-strategic training.
PMID- 29348434
TI - Identification of genetic elements in metabolism by high-throughput mouse
phenotyping.
AB - Metabolic diseases are a worldwide problem but the underlying genetic factors and
their relevance to metabolic disease remain incompletely understood. Genome-wide
research is needed to characterize so-far unannotated mammalian metabolic genes.
Here, we generate and analyze metabolic phenotypic data of 2016 knockout mouse
strains under the aegis of the International Mouse Phenotyping Consortium (IMPC)
and find 974 gene knockouts with strong metabolic phenotypes. 429 of those had no
previous link to metabolism and 51 genes remain functionally completely
unannotated. We compared human orthologues of these uncharacterized genes in five
GWAS consortia and indeed 23 candidate genes are associated with metabolic
disease. We further identify common regulatory elements in promoters of candidate
genes. As each regulatory element is composed of several transcription factor
binding sites, our data reveal an extensive metabolic phenotype-associated
network of co-regulated genes. Our systematic mouse phenotype analysis thus paves
the way for full functional annotation of the genome.
PMID- 29348441
TI - SDF1 gradient associates with the distribution of c-Kit+ cardiac cells in the
heart.
AB - Identification of the adult cardiac stem cells (CSCs) has offered new therapeutic
possibilities for treating ischemic myocardium. CSCs positive for the cell
surface antigen c-Kit are known as the primary source for cardiac regeneration.
Accumulating evidence shows that chemokines play important roles in stem cell
homing. Here we investigated molecular targets to be utilized in modulating the
mobility of endogenous CSCs. In a four week follow-up after experimental acute
myocardial infarction (AMI) with ligation of the left anterior descending (LAD)
coronary artery of Sprague-Dawley rats c-Kit+ CSCs redistributed in the heart.
The number of c-Kit+ CSCs in the atrial c-Kit niche was diminished, whereas
increased amount was observed in the left ventricle and apex. This was associated
with increased expression of stromal cell-derived factor 1 alpha (SDF1alpha), and
a significant positive correlation was found between c-Kit+ CSCs and SDF1alpha
expression in the heart. Moreover, the migratory capacity of isolated c-Kit+ CSCs
was induced by SDF1 treatment in vitro. We conclude that upregulation of
SDF1alpha after AMI associates with increased expression of endogenous c-Kit+
CSCs in the injury area, and show induced migration of c-Kit+ cells by SDF1.
PMID- 29348442
TI - A neutral ceramidase, NlnCDase, is involved in the stress responses of brown
planthopper, Nilaparvata lugens (Stal).
AB - Ceramidases (CDases) are vital enzymes involved in the biosynthesis of
sphingolipids, which are essential components of eukaryotic membranes. The
function of these enzymes in insects, however, is poorly understood. We
identified a neutral ceramidase (NlnCDase) from the brown planthopper,
Nilaparvata lugens, one of the most destructive hemipteran pests of rice. The C12
ceramide was the most preferred substrate for the NlnCDase enzyme. The activity
of the NlnCDase enzyme was highest in the neutral-pH range (pH 6.0). It was
inhibited by EGTA, Cs+ and Fe2+, while stimulated by EDTA and Ca2+. Moreover, the
NlnCDase has higher transcript level and activity in adults than in eggs and
nymphs, and in the reproductive organs (ovaries and spermaries) than in other
tissues (i.e. heads, thorax, legs, midguts), which suggested that the NlnCDase
might be elevated to mediate developmental process. In addition, transcripts and
activity of the NlnCDase were up-regulated under abiotic stresses including
starvation, abnormal temperature, and insecticides, and biotic stress of
resistant rice varieties. Knocking down NlnCDase by RNA interference increased
female survival under starvation and temperature stresses, suggesting that
NlnCDase might be involved in the stress response in N. lugens.
PMID- 29348444
TI - ToxicDocs (www.ToxicDocs.org): from history buried in stacks of paper to open,
searchable archives online.
AB - As a result of a legal mechanism called discovery, the authors accumulated
millions of internal corporate and trade association documents related to the
introduction of new products and chemicals into workplaces and commerce. What did
these private entities discuss among themselves and with their experts? The
plethora of documents, both a blessing and a curse, opened new sources and
interesting questions about corporate and regulatory histories. But they also
posed an almost insurmountable challenge to historians. Thus emerged ToxicDocs,
possible only with a technological innovation known as "Big Data." That refers to
the sheer volume of new digital data and to the computational power to analyze
them. Users will be able to identify what firms knew (or did not know) about the
dangers of toxic substances in their products-and when. The database opens many
areas to inquiry including environmental studies, business history, government
regulation, and public policy. ToxicDocs will remain a resource free and open to
all, anywhere in the world.
PMID- 29348445
TI - ToxicDocs: a new resource for assessing the impact of corporate practices on
health.
PMID- 29348443
TI - A general and flexible method for signal extraction from single-cell RNA-seq
data.
AB - Single-cell RNA-sequencing (scRNA-seq) is a powerful high-throughput technique
that enables researchers to measure genome-wide transcription levels at the
resolution of single cells. Because of the low amount of RNA present in a single
cell, some genes may fail to be detected even though they are expressed; these
genes are usually referred to as dropouts. Here, we present a general and
flexible zero-inflated negative binomial model (ZINB-WaVE), which leads to low
dimensional representations of the data that account for zero inflation
(dropouts), over-dispersion, and the count nature of the data. We demonstrate,
with simulated and real data, that the model and its associated estimation
procedure are able to give a more stable and accurate low-dimensional
representation of the data than principal component analysis (PCA) and zero
inflated factor analysis (ZIFA), without the need for a preliminary normalization
step.
PMID- 29348446
TI - ToxicDocs (www.ToxicDocs.org) goes live: A giant step toward leveling the playing
field for efforts to combat toxic exposures.
PMID- 29348447
TI - Browsing a corporation's mind.
PMID- 29348449
TI - ToxicDocs and the fight against biased public health science worldwide.
PMID- 29348448
TI - Archival sources on asbestos and silicosis in Southern Africa and Australia.
PMID- 29348450
TI - The value of not being lost in our digital world.
PMID- 29348451
TI - ToxicDocs: using the US legal system to confront industries' systematic
counterattacks against public health.
PMID- 29348452
TI - Combination Therapy Strategy of Quorum Quenching Enzyme and Quorum Sensing
Inhibitor in Suppressing Multiple Quorum Sensing Pathways of P. aeruginosa.
AB - The threat of antibiotic resistant bacteria has called for alternative
antimicrobial strategies that would mitigate the increase of classical resistance
mechanism. Many bacteria employ quorum sensing (QS) to govern the production of
virulence factors and formation of drug-resistant biofilms. Targeting the
mechanism of QS has proven to be a functional alternative to conventional
antibiotic control of infections. However, the presence of multiple QS systems in
individual bacterial species poses a challenge to this approach. Quorum sensing
inhibitors (QSI) and quorum quenching enzymes (QQE) have been both investigated
for their QS interfering capabilities. Here, we first simulated the combination
effect of QQE and QSI in blocking bacterial QS. The effect was next validated by
experiments using AiiA as QQE and G1 as QSI on Pseudomonas aeruginosa LasR/I and
RhlR/I QS circuits. Combination of QQE and QSI almost completely blocked the P.
aeruginosa las and rhl QS systems. Our findings provide a potential chemical
biology application strategy for bacterial QS disruption.
PMID- 29348453
TI - Enhanced anastomotic healing by Daikenchuto (TJ-100) in rats.
AB - Daikenchuto (DKT), a traditional Japanese medicine, is widely used to treat
various gastrointestinal disorders. This study aimed to investigate whether DKT
could promote the anastomotic healing in a rat model. Pedicled colonic segments
were made in left colon by ligation of the feeding arteries, and then intestinal
continuity was restored. Colonic blood flow was analyzed by using ICG
fluorescence imaging: Fmax, Tmax, T1/2, and Slope were calculated. Anastomotic
leakage (AL) was found in 6 of 19 rats (31.6%) in the control group, whereas in 1
of 16 rats (6.2%) in the DKT group. The Fmax and Slope of DKT group were
significantly higher than those of control group. DKT could promote the
anastomotic healing, with the higher bursting pressure on postoperative day (POD)
2 and 5, the larger granulation thickness on POD 5, and neoangiogenesis on POD 5.
Histological examination showed DKT exhibited a decreased inflammatory cell
infiltration, enhanced fibroblast infiltration, and enhanced collagen density on
POD 5. In the DKT group, the levels of TGFbeta1 on POD 2 and VEGFalpha on POD5
were significantly higher, whereas the level of TNFalpha on POD 2 was
significantly lower. Therefore, DKT could be effective for the prevention of AL
following colorectal surgery.
PMID- 29348454
TI - Harnessing insulin- and leptin-induced oxidation of PTP1B for therapeutic
development.
AB - The protein tyrosine phosphatase PTP1B is a major regulator of glucose
homeostasis and energy metabolism, and a validated target for therapeutic
intervention in diabetes and obesity. Nevertheless, it is a challenging target
for inhibitor development. Previously, we generated a recombinant antibody
(scFv45) that recognizes selectively the oxidized, inactive conformation of
PTP1B. Here, we provide a molecular basis for its interaction with reversibly
oxidized PTP1B. Furthermore, we have identified a small molecule inhibitor that
mimics the effects of scFv45. Our data provide proof-of-concept that
stabilization of PTP1B in an inactive, oxidized conformation by small molecules
can promote insulin and leptin signaling. This work illustrates a novel paradigm
for inhibiting the signaling function of PTP1B that may be exploited for
therapeutic intervention in diabetes and obesity.
PMID- 29348455
TI - Programmed cell death can increase the efficacy of microbial bet -hedging.
AB - Programmed cell death (PCD) occurs in both unicellular and multicellular
organisms. While PCD plays a key role in the development and maintenance of
multicellular organisms, explaining why single-celled organisms would evolve to
actively commit suicide has been far more challenging. Here, we explore the
potential for PCD to act as an accessory to microbial bet-hedging strategies that
utilize stochastic phenotype switching. We consider organisms that face
unpredictable and recurring disasters, in which fitness depends on effective
phenotypic diversification. We show that when reproductive opportunities are
limited by carrying capacity, PCD drives population turnover, providing increased
opportunities for phenotypic diversification through stochastic phenotype
switching. The main cost of PCD, providing resources for growth to a PCD(-)
competitor, is ameliorated by genetic assortment in spatially structured
populations. Using agent -based simulations, we explore how basic demographic
factors, namely bottlenecks and local dispersal, can generate sufficient spatial
structure to favor the evolution of high PCD rates.
PMID- 29348456
TI - TWIST1 induces expression of discoidin domain receptor 2 to promote ovarian
cancer metastasis.
AB - The mesenchymal gene program has been shown to promote the metastatic progression
of ovarian cancer; however, specific proteins induced by this program that lead
to these metastatic behaviors have not been identified. Using patient derived
tumor cells and established human ovarian tumor cell lines, we find that the
Epithelial-to-Mesenchymal Transition inducing factor TWIST1 drives expression of
discoidin domain receptor 2 (DDR2), a receptor tyrosine kinase (RTK) that
recognizes fibrillar collagen as ligand. The expression and action of DDR2 was
critical for mesothelial cell clearance, invasion and migration in ovarian tumor
cells. It does so, in part, by upregulating expression and activity of matrix
remodeling enzymes that lead to increased cleavage of fibronectin and spreading
of tumor cells. Additionally, DDR2 stabilizes SNAIL1, allowing for sustained
mesenchymal phenotype. In patient derived ovarian cancer specimens, DDR2
expression correlated with enhanced invasiveness. DDR2 expression was associated
with advanced stage ovarian tumors and metastases. In vivo studies demonstrated
that the presence of DDR2 is critical for ovarian cancer metastasis. These
findings indicate that the collagen receptor DDR2 is critical for multiple steps
of ovarian cancer progression to metastasis, and thus, identifies DDR2 as a
potential new target for the treatment of metastatic ovarian cancer.
PMID- 29348457
TI - LTBP3 promotes early metastatic events during cancer cell dissemination.
AB - Latent transforming growth factor beta (TGFbeta)-binding proteins (LTBPs) are
important for the secretion, activation, and function of mature TGFbeta,
especially so in cancer cell physiology. However, specific roles of the LTBPs
remain understudied in the context of the primary tumor microenvironment. Herein,
we investigated the role of LTBP3 in the distinct processes involved in cancer
metastasis. By using three human tumor cell lines of different tissue origin
(epidermoid HEp-3 and prostate PC-3 carcinomas and HT-1080 fibrosarcoma) and
several metastasis models conducted in both mammalian and avian settings, we show
that LTBP3 is involved in the early dissemination of primary cancer cells, namely
in the intravasation step of the metastatic cascade. Knockdown of LTBP3 in all
tested cell lines led to significant inhibition of tumor cell intravasation, but
did not affect primary tumor growth. LTBP3 was dispensable in the late steps of
carcinoma cell metastasis that follow tumor cell intravasation, including
vascular arrest, extravasation, and tissue colonization. However, LTBP3 depletion
diminished the angiogenesis-inducing potential of HEp-3 cells in vivo, which was
restorable by exogenous delivery of LTBP3 protein. A similar compensatory
approach rescued the dampened intravasation of LTBP3-deficient HEp-3 cells,
suggesting that LTBP3 regulates the induction of the intravasation-supporting
angiogenic vasculature within developing primary tumors. Using our recently
developed microtumor model, we confirmed that LTBP3 loss resulted in the
development of intratumoral vessels with an abnormal microarchitecture
incompatible with efficient intravasation of HEp-3 carcinoma cells. Collectively,
these findings demonstrate that LTBP3 represents a novel oncotarget that has
distinctive functions in the regulation of angiogenesis-dependent tumor cell
intravasation, a critical process during early cancer dissemination. Our
experimental data are also consistent with the survival prognostic value of LTBP3
expression in early-stage head and neck squamous cell carcinomas, further
indicating a specific role for LTBP3 in cancer progression toward metastatic
disease.
PMID- 29348458
TI - Hic-5 regulates fibrillar adhesion formation to control tumor extracellular
matrix remodeling through interaction with tensin1.
AB - The linearization of the stromal extracellular matrix (ECM) by cancer-associated
fibroblasts (CAFs) facilitates tumor cell growth and metastasis. However, the
mechanism by which the ECM is remodeled is not fully understood. Hic-5
(TGFbeta1i1), a focal adhesion scaffold protein, has previously been reported to
be crucial for stromal ECM deposition and remodeling in vivo. Herein we show that
CAFs lacking Hic-5 exhibit a significant reduction in the ability to form
fibrillar adhesions, a specialized form of focal adhesion that promote
fibronectin fibrillogenesis. Hic-5 was found to promote fibrillar adhesion
formation through a newly characterized interaction with tensin1. Furthermore,
Src-dependent phosphorylation of Hic-5 facilitated the interaction with tensin1
to prevent beta1 integrin internalization and trafficking to the lysosome. The
interaction between Hic-5 and tensin1 was mechanosensitive, promoting fibrillar
adhesion formation and fibronectin fibrillogenesis in a rigidity-dependent
fashion. Importantly, this Src-dependent mechanism was conserved in three
dimensional (3D) ECM environments. Immunohistochemistry of tensin1 showed
enrichment in CAFs in vivo, which was abrogated upon deletion of Hic-5.
Interestingly, elevated Hic-5 expression correlates with reduced distant
metastasis-free survival in patients with basal-like, HER2+ and grade 3 tumors.
Thus, we have identified Hic-5 as a crucial regulator of ECM remodeling in CAFs
by promoting fibrillar adhesion formation through a novel interaction with
tensin1.
PMID- 29348459
TI - Distinct dependencies on receptor tyrosine kinases in the regulation of MAPK
signaling between BRAF V600E and non-V600E mutant lung cancers.
AB - BRAF is one of the most frequently mutated genes across a number of different
cancers, with the best-characterized mutation being V600E. Despite the successes
of treating BRAF mutant V600E lung cancer with BRAF pathway inhibitors, treatment
strategies targeting tumors with non-V600E mutations are yet to be established.
We studied cellular signaling differences between lung cancers with different
BRAF mutations and determined their sensitivities to BRAF pathway inhibitors.
Here, we observed that MEK inhibition induced feedback activation of the receptor
tyrosine kinase (RTK) EGFR, and in some cases the RTK FGFR, resulting in
transient suppression of ERK phosphorylation in BRAF non-V600E, but not BRAF
V600E, mutant cells. Furthermore, we found that both EGFR and FGFR activated the
MEK/ERK pathway, despite the presence of BRAF non-V600E mutations with elevated
kinase activity. Moreover, in BRAF non-V600E mutants with impaired kinase
activities, EGFR had even greater control over the MEK/ERK pathway, essentially
contributing completely to the tonic mitogen-activated protein kinase (MAPK)
signal. Accordingly, the combination of MEK inhibitor with EGFR inhibitor was
effective at shrinking tumors in mouse model of BRAF non-V600E mutant lung
cancer. Furthermore, the results were recapitulated with a clinically relevant
dual inhibitor of EGFR and RAF, BGB-283. Overall, although BRAF V600E mutant
cells are sensitive to BRAF inhibition, non-V600E mutant cancer cells are reliant
on RTKs for their MAPK activation and inhibiting both MEK and RTKs are necessary
in these cancers. Our findings provide evidence of critical survival signals in
BRAF non-V600E mutant cancers, which could pave the way for effective treatment
of these cancers.
PMID- 29348460
TI - FYN promotes mesenchymal phenotypes of basal type breast cancer cells through
STAT5/NOTCH2 signaling node.
AB - Basal type breast cancer is the most aggressive and has mesenchymal features with
a high metastatic ability. However, the signaling node that determines the basal
type features in breast cancer remains obscure. Here, we report that FYN among
SRC family kinases is required for the maintenance of basal type breast cancer
subtype. Importantly, FYN enhanced NOTCH2 activation in basal type breast cancer
cells through STAT5-mediated upregulation of Jagged-1 and DLL4 NOTCH ligands,
thereby contributed to mesenchymal phenotypes. In addition, we found that high
levels of FYN persist in basal type breast cancer cells by a positive feedback
loop between FYN and STAT5. FYN interacted directly with STAT5 and increased p
STAT5 that further acts as a transcription factor for FYN. Taken together, our
findings demonstrate a pivotal role of FYN and its downstream effectors in
maintaining the basal type features in breast cancer.
PMID- 29348461
TI - Loss of Cdk5 in breast cancer cells promotes ROS-mediated cell death through
dysregulation of the mitochondrial permeability transition pore.
AB - Cdk5, which plays a role in the development and progression of many human
cancers, localizes in the mitochondria, a key determinant of apoptotic cell
death. Cdk5 is upregulated in breast cancer cells but it was shown that Cdk5 loss
increases chemotherapy-induced apoptosis. However, the molecular mechanism by
which Cdk5 loss promotes cell death remains unclear. Here, we investigate the
possibility that Cdk5 loss activates the intrinsic apoptotic pathway in breast
cancer cells. We demonstrate that Cdk5-deficient breast cancer cells exhibit
increased mitochondrial depolarization, mitochondrial ROS levels, and
mitochondrial fragmentation that is associated with an increase in both
intracellular Ca2+ level and calcineurin activity, and DRP1 S637
dephosphorylation. These events accompany increased apoptosis, indicating that
Cdk5 loss promotes mitochondria-mediated apoptosis. To define this apoptotic
pathway, we utilized various inhibitors of mitochondrial function. Apoptosis is
completely prevented by mPTP inhibition, almost fully inhibited by blocking ROS
and unaffected by inhibition of mitochondrial fission, suggesting that apoptosis
in breast cancer cells due to Cdk5 loss occurs via a novel mPTP-dependent
mechanism that acts primarily through ROS increase.
PMID- 29348462
TI - Piperlongumine and p53-reactivator APR-246 selectively induce cell death in HNSCC
by targeting GSTP1.
AB - TP53 mutations frequently occur in head and neck squamous cell carcinoma (HNSCC)
patients without human papillomavirus infection. The recurrence rate for these
patients is distinctly high. It has been actively explored to identify agents
that target TP53 mutations and restore wild-type (WT) TP53 activities in HNSCC.
PRIMA-1 (p53-reactivation and induction of massive apoptosis-1) and its
methylated analogue PRIMA-1Met (also called APR-246) were found to be able to
reestablish the DNA-binding activity of p53 mutants and reinstate the functions
of WT p53. Herein we report that piperlongumine (PL), an alkaloid isolated from
Piper longum L., synergizes with APR-246 to selectively induce apoptosis and
autophagic cell death in HNSCC cells, whereas primary and immortalized mouse
embryonic fibroblasts and spontaneously immortalized non-tumorigenic human skin
keratinocytes (HaCat) are spared from the damage by the co-treatment.
Interestingly, PL-sensitized HNSCC cells to APR-246 are TP53 mutation
independent. Instead, we demonstrated that glutathione S-transferase pi 1
(GSTP1), a GST family member that catalyzes the conjugation of GSH with
electrophilic compounds to fulfill its detoxification function, is highly
expressed in HNSCC tissues. Administration of PL and APR-246 significantly
suppresses GSTP1 activity, resulting in the accumulation of ROS, depletion of
GSH, elevation of GSSG, and DNA damage. Ectopic expression of GSTP1 or pre
treatment with antioxidant N-acetyl-L-cysteine (NAC) abrogates the ROS elevation
and decreases DNA damage, apoptosis, and autophagic cell death prompted by PL/APR
246. In addition, administration of PL and APR-246 impedes UMSCC10A xenograft
tumor growth in SCID mice. Taken together, our data suggest that HNSCC cells are
selectively sensitive to the combination of PL and APR-246 due to a remarkably
synergistic effect of the co-treatment in the induction of ROS by suppression of
GSTP1.
PMID- 29348463
TI - The bone microstructure of polar "hypsilophodontid" dinosaurs from Victoria,
Australia.
AB - High-latitude (i.e., "polar") Mesozoic fauna endured months of twilight and
relatively low mean annual temperatures. Yet non-avian dinosaurs flourished in
this taxing environment. Fossils of basal ornithopod dinosaurs
("hypsilophodontids") are common in the Early Cretaceous high-latitude sediments
of Victoria, Australia, and four taxa have been described; although their
ontogenetic histories are largely unexplored. In the present study, eighteen
tibiae and femora were utilized in the first multi-specimen ontogenetic
histological analysis of Australian polar hypsilophodontids. The sample consists
of eleven individuals from the Flat Rocks locality (Late Valanginian or
Barremian), and five from the Dinosaur Cove locality (Albian). In both groups,
growth was most rapid during the first three years, and skeletal maturity
occurred between five and seven years. There is a weak asymptotic trend in a plot
of growth mark count versus femur length, with considerable individual variation.
Histology suggests two genera are present within the Dinosaur Cove sample, but
bone microstructure alone could not distinguish genera within the Flat Rocks
sample, or across the two geologically separate (~ 26 Ma) localities. Additional
histologic sampling, combined with morphological analyses, may facilitate further
differentiation between ontogenetic, individual, and species variation.
PMID- 29348464
TI - 150,000-year palaeoclimate record from northern Ethiopia supports early, multiple
dispersals of modern humans from Africa.
AB - Climatic change is widely acknowledged to have played a role in the dispersal of
modern humans out of Africa, but the timing is contentious. Genetic evidence
links dispersal to climatic change ~60,000 years ago, despite increasing evidence
for earlier modern human presence in Asia. We report a deep seismic and near
continuous core record of the last 150,000 years from Lake Tana, Ethiopia, close
to early modern human fossil sites and to postulated dispersal routes. The record
shows varied climate towards the end of the penultimate glacial, followed by an
abrupt change to relatively stable moist climate during the last interglacial.
These conditions could have favoured selection for behavioural versatility,
population growth and range expansion, supporting models of early, multiple
dispersals of modern humans from Africa.
PMID- 29348465
TI - Publisher Correction: EFHD2 promotes epithelial-to-mesenchymal transition and
correlates with postsurgical recurrence of stage I lung adenocarcinoma.
AB - A correction to this article has been published and is linked from the HTML
version of this paper. The error has been fixed in the paper.
PMID- 29348466
TI - Gender specific association of parathyroid hormone and vitamin D with metabolic
syndrome in population with preserved renal function.
AB - The association of parathyroid hormone (PTH) and vitamin D with Metabolic
syndrome (MetS) was evaluated using representative data from the Korean
population. Data from 7004 subjects aged 50 or older with preserved renal
function (excluding chronic kidney disease stage 3b to 5) who were included in
the Korean National Health and Nutrition Examination Survey between 2008 and 2010
were analysed. Higher PTH levels (pg/ml) were observed in subjects with MetS than
in those without MetS among both genders (60.1 (58.6-61.6) vs. 62.4 (60.7-64.2)
in males p = 0.018, 60.7 (59.4-62.1) vs. 63.9 (62.4-65.6) in females, p < 0.001).
For females, PTH levels were significantly higher in subjects with MetS than in
those without MetS after adjustment for possible covariates. Lower 25(OH)D levels
were significantly associated with MetS only in male subjects (p = 0.004). As the
number of MetS components increased, a significant rise in PTH levels (p for
trend 0.005 in males and 0.024 in females) and a decrease in 25(OH)D levels (p
for trend < 0.001 in males and 0.053 in females) were observed. In conclusion,
among subjects with preserved renal function, PTH levels were possibly associated
with MetS in females, whereas vitamin D levels exhibited a possible link to MetS
in males.
PMID- 29348467
TI - Efficacy of MEK inhibition in a K-Ras-driven cholangiocarcinoma preclinical
model.
AB - Intrahepatic cholangiocarcinoma (iCCA) is a deadly malignancy with limited
treatment options. Gain-of-function mutations in K-Ras is a very frequent
alteration, occurring in ~15 to 25% of human iCCA patients. Here, we established
a new iCCA model by expressing activated forms of Notch1 (NICD) and K-Ras (K
RasV12D) in the mouse liver (K-Ras/NICD mice). Furthermore, we investigated the
therapeutic potential of MEK inhibitors in vitro and in vivo using human CCA cell
lines and K-Ras/NICD mice, respectively. Treatment with U0126, PD901, and
Selumetinib MEK inhibitors triggered growth restraint in all CCA cell lines
tested, with the most pronounced growth suppressive effects being observed in K
Ras mutant cells. Growth inhibition was due to reduction in proliferation and
massive apoptosis. Furthermore, treatment of K-Ras/NICD tumor-bearing mice with
PD901 resulted in stable disease. At the molecular level, PD901 efficiently
inhibited ERK activation in K-Ras/NICD tumor cells, mainly leading to increased
apoptosis. Altogether, our study demonstrates that K-Ras/NICD mice represent a
novel and useful preclinical model to study K-Ras-driven iCCA development and the
effectiveness of MEK inhibitors in counteracting this process. Our data support
the usefulness of MEK inhibitors for the treatment of human iCCA.
PMID- 29348468
TI - The potential impact of invasive woody oil plants on protected areas in China
under future climate conditions.
AB - Biodiesel produced from woody oil plants is considered a green substitute for
fossil fuels. However, a potential negative impact of growing woody oil plants on
a large scale is the introduction of highly invasive species into susceptible
regions. In this study, we examined the potential invasion risk of woody oil
plants in China's protected areas under future climate conditions. We simulated
the current and future potential distributions of three invasive woody oil
plants, Jatropha curcas, Ricinus communis, and Aleurites moluccana, under two
climate change scenarios (RCP2.6 and RCP8.5) up to 2050 using species
distribution models. Protected areas in China that will become susceptible to
these species were then identified using a spatial overlay analysis. Our results
showed that by 2050, 26 and 41 protected areas would be threatened by these
invasive woody oil plants under scenarios RCP2.6 and RCP8.5, respectively. A
total of 10 unique forest ecosystems and 17 rare plant species could be
potentially affected. We recommend that the invasive potential of woody oil
plants be fully accounted for when developing forest-based biodiesel, especially
around protected areas.
PMID- 29348469
TI - Treprostinil inhibits proliferation and extracellular matrix deposition by
fibroblasts through cAMP activation.
AB - Idiopathic pulmonary fibrosis (IPF) is characterized by peripheral lung fibrosis
and increased interstitial extracellular matrix (ECM) deposition. In IPF, tumor
growth factor (TGF)-beta1 which is the major stimulus of ECM deposition, and
platelet derived growth factor (PDGF)-BB is a potent stimulus of fibrosis. Thus,
the effect of Treprostinil on TGF-beta1 and PDGF-induced fibroblast proliferation
and ECM deposition was investigated. Human peripheral lung fibroblasts of seven
IPF patients and five lung donors were stimulated by PDGF, or TGF-beta1, or the
combination. Cells were pre-incubated (30 min) with either Treprostinil,
forskolin, di-deoxyadenosine (DDA), or vehicle. Treprostinil time dependently
activated cAMP thereby preventing PDGF-BB induced proliferation and TGF-beta1
secretion. Cell counts indicated proliferation; alpha-smooth muscle actin (alpha
SMA) indicted differentiation, and collagen type-1 or fibronectin deposition
remodeling. Myo-fibroblast indicating alpha-SMA expression was significantly
reduced and its formation was altered by Treprostinil. Collagen type-I and
fibronectin deposition were also reduced by Treprostinil. The effect of
Treprostinil on collagen type-I deposition was cAMP sensitive as it was
counteracted by DDA, while the effect on fibronectin was not cAMP mediated.
Treprostinil antagonized the pro-fibrotic effects of both PDGF-BB and TGF-beta1
in primary human lung fibroblasts. The data presented propose a therapeutic
relevant anti-fibrotic effect of Treprostinil in IPF.
PMID- 29348470
TI - Fibroblast growth factor 21 increases insulin sensitivity through specific
expansion of subcutaneous fat.
AB - Although the pharmacological effects of fibroblast growth factor 21 (FGF21) are
well-documented, uncertainty about its role in regulating excessive energy intake
remains. Here, we show that FGF21 improves systemic insulin sensitivity by
promoting the healthy expansion of subcutaneous adipose tissue (SAT). Serum FGF21
levels positively correlate with the SAT area in insulin-sensitive obese
individuals. FGF21 knockout mice (FGF21KO) show less SAT mass and are more
insulin-resistant when fed a high-fat diet. Replenishment of recombinant FGF21 to
a level equivalent to that in obesity restores SAT mass and reverses insulin
resistance in FGF21KO, but not in adipose-specific betaklotho knockout mice.
Moreover, transplantation of SAT from wild-type to FGF21KO mice improves insulin
sensitivity in the recipients. Mechanistically, circulating FGF21 upregulates
adiponectin in SAT, accompanied by an increase of M2 macrophage polarization. We
propose that elevated levels of endogenous FGF21 in obesity serve as a defense
mechanism to protect against systemic insulin resistance.
PMID- 29348471
TI - Three Dimensional Evaluation of Posterior Pole and Optic Nerve Head in Tilted
Disc.
AB - For over a century, tilted disc syndrome (TDS) has been defined vaguely. The lack
of consensus of the terminology arises from the lack of understanding of the
pathogenesis of this condition. Also, myopic discs with temporal crescents or
peripapillary atrophy (PPA) are histologically indistinguishable from TDS.
Therefore, we examined the morphological background of the extreme ONH
appearances such as the myopic tilted disc and the TDS by analyzing the posterior
segment of the eye from a three-dimensional (3D) perspective. 107 eyes of 107
subjects were classified into 3 groups with respect to the optic disc torsion
degrees: (1) mild torsion (0-30 degrees; 35 eyes) and (2) moderate torsion (30-60
degrees; 35 eyes) and (3) severe torsion (60-90 degrees; 37 eyes). SSOCT images
were analyzed in coronal view, which supplements anterior-posterior depth (z axis
in Cartesian coordinates). The amount of optic disc torsion was significantly
correlated with Disc-DPE angle and Fovea-Disc depth (r = 0.548, P < 0.001 and r =
0.544, P < 0.001). In conclusion, we describe specific types of posterior sclera
configuration that corresponds to the increasing degree of optic disc torsion,
even in the extreme ONH appearances such as the myopic tilted disc and the TDS.
These findings suggest that the optic disc appearance is determined by the
configuration of the posterior sclera.
PMID- 29348473
TI - Gene therapy: Autoimmune diabetes reversed in mice.
PMID- 29348474
TI - Adrenal disease: Imitating the cortisol profile improves the immune system.
PMID- 29348472
TI - Viral highway to nucleus exposed by image correlation analyses.
AB - Parvoviral genome translocation from the plasma membrane into the nucleus is a
coordinated multistep process mediated by capsid proteins. We used fast confocal
microscopy line scan imaging combined with image correlation methods including
auto-, pair- and cross-correlation, and number and brightness analysis, to study
the parvovirus entry pathway at the single-particle level in living cells. Our
results show that the endosome-associated movement of virus particles fluctuates
from fast to slow. Fast transit of single cytoplasmic capsids to the nuclear
envelope is followed by slow movement of capsids and fast diffusion of capsid
fragments in the nucleoplasm. The unique combination of image analyses allowed us
to follow the fate of intracellular single virus particles and their interactions
with importin beta revealing previously unknown dynamics of the entry pathway.
PMID- 29348475
TI - Osteoporosis: Community-based screening reduces hip fracture risk.
PMID- 29348477
TI - Thyroid cancer: Balancing benefit and risk in TSH management of DTC.
PMID- 29348478
TI - Metabolism: Leptin's role in starvation.
PMID- 29348479
TI - Prime-boost vaccination with recombinant protein and adenovirus-vector expressing
Plasmodium vivax circumsporozoite protein (CSP) partially protects mice against
Pb/Pv sporozoite challenge.
AB - Vaccine development against Plasmodium vivax malaria lags behind that for
Plasmodium falciparum. To narrow this gap, we administered recombinant antigens
based on P. vivax circumsporozoite protein (CSP) to mice. We expressed in Pichia
pastoris two chimeric proteins by merging the three central repeat regions of
different CSP alleles (VK210, VK247, and P. vivax-like). The first construct
(yPvCSP-AllFL) contained the fused repeat regions flanked by N- and C-terminal
regions. The second construct (yPvCSP-AllCT) contained the fused repeat regions
and the C-terminal domain, plus RI region. Mice were vaccinated with three doses
of yPvCSP in adjuvants Poly (I:C) or Montanide ISA720. We also used replication
defective adenovirus vectors expressing CSP of human serotype 5 (AdHu5) and
chimpanzee serotype 68 (AdC68) for priming mice which were subsequently boosted
twice with yPvCSP proteins in Poly (I:C) adjuvant. Regardless of the regime used,
immunized mice generated high IgG titres specific to all CSP alleles. After
challenge with P. berghei ANKA transgenic parasites expressing Pb/PvVK210 or
Pb/PvVK247 sporozoites, significant time delays for parasitemia were observed in
all vaccinated mice. These vaccine formulations should be clinically tried for
their potential as protective universal vaccine against P. vivax malaria.
PMID- 29348480
TI - Association between plasma concentrations of branched-chain amino acids and
adipokines in Japanese adults without diabetes.
AB - Previous studies have consistently reported an association between circulating
levels of branched-chain amino acids (BCAAs) or adipokines and insulin
resistance; however, the association between BCAA and adipokine levels remains to
be clarified. In this cross-sectional study involving 678 participants (435 men)
without diabetes, plasma BCAA (valine, leucine, and isoleucine), adipokine (total
and high molecular weight [HMW] adiponectin, leptin, and tumor necrosis factor
alpha [TNF-alpha]) concentrations, and an updated homeostasis model assessment of
insulin resistance (HOMA2-IR) were measured. The association between the
concentrations of total BCAAs and adipokines was adjusted for confounding
factors, including body mass index. For the lowest and highest BCAA quartiles,
the adjusted geometric mean levels of HMW adiponectin were, respectively, 1.51
and 0.91 MUg/mL, in men (P for trend < 0.0001); 3.61 and 2.29 MUg/mL, in women (P
= 0.0005). The corresponding geometric mean levels for leptin were 1681 and 2620
pg/mL, in men (P = 0.003), and 4270 and 6510 pg/mL, in women (P = 0.003). Those
for HOMA2-IR were 0.89 and 1.11, in men (P < 0.0001), and 0.79 and 0.96, in women
(P < 0.0001); no significant association was found with TNF-alpha. These results
suggest significant associations between BCAA concentrations and those for
adiponectin, leptin and HOMA2-IR in individuals without diabetes.
PMID- 29348481
TI - Effects of graphene intercalation on dielectric reliability of HfO2 and
modulation of effective work function for Ni/Gr/c-HfO2 interfaces: first
principles study.
AB - We have investigated the effects of graphene intercalation on dielectric
reliability of HfO2 for Ni/Gr/HfO2 interfaces, and the effects of graphene
intercalation and interfacial atom vacancy on the effective work function (EWF)
of Ni/Gr/HfO2 interfaces using first-principle calculation based on density
functional theory. The calculated results indicate that graphene intercalation
can improve dielectric reliability of HfO2 dielectric even for the interfaces
having interfacial oxygen vacancy or a small amount carbon vacancy. Moreover, the
calculated results indicate that, inserting graphene into Ni/HfO2 interface
induces the EWF's to decline, and controlling interfacial oxygen or carbon
vacancy can effectively tune the EWF of Ni/Gr/HfO2 interface. Our work strongly
suggests that the use of graphene synthesized into Ni/HfO2 interface is a very
effective way to improve the interface quality, and controlling interfacial
oxygen or carbon vacancy is also an attractive and promising way for modulating
the EWF of Ni/Gr/HfO2 interfaces.
PMID- 29348476
TI - Animal models of obesity and diabetes mellitus.
AB - More than one-third of the worldwide population is overweight or obese and
therefore at risk of developing type 2 diabetes mellitus. In order to mitigate
this pandemic, safer and more potent therapeutics are urgently required. This
necessitates the continued use of animal models to discover, validate and
optimize novel therapeutics for their safe use in humans. In order to improve the
transition from bench to bedside, researchers must not only carefully select the
appropriate model but also draw the right conclusions. In this Review, we
consolidate the key information on the currently available animal models of
obesity and diabetes and highlight the advantages, limitations and important
caveats of each of these models.
PMID- 29348482
TI - EGFR activation triggers cellular hypertrophy and lysosomal disease in NAGLU
depleted cardiomyoblasts, mimicking the hallmarks of mucopolysaccharidosis IIIB.
AB - Mucopolysaccharidosis (MPS) IIIB is an inherited lysosomal storage disease caused
by the deficiency of the enzyme alpha-N-acetylglucosaminidase (NAGLU) required
for heparan sulfate (HS) degradation. The defective lysosomal clearance of
undigested HS results in dysfunction of multiple tissues and organs. We recently
demonstrated that the murine model of MPS IIIB develops cardiac disease, valvular
abnormalities, and ultimately heart failure. To address the molecular mechanisms
governing cardiac dysfunctions in MPS IIIB, we generated a model of the disease
by silencing NAGLU gene expression in H9C2 rat cardiomyoblasts. NAGLU-depleted
H9C2 exhibited accumulation of abnormal lysosomes and a hypertrophic phenotype.
Furthermore, we found the specific activation of the epidermal growth factor
receptor (EGFR), and increased phosphorylation levels of extracellular signal
regulated kinases (ERKs) in NAGLU-depleted H9C2. The inhibition of either EGFR or
ERKs, using the selective inhibitors AG1478 and PD98059, resulted in the
reduction of both lysosomal aberration and hypertrophy in NAGLU-depleted H9C2. We
also found increased phosphorylation of c-Src and a reduction of the hypertrophic
response in NAGLU-depleted H9C2 transfected with a dominant-negative c-Src.
However, c-Src phosphorylation remained unaffected by AG1478 treatment, posing c
Src upstream EGFR activation. Finally, heparin-binding EGF-like growth factor (HB
EGF) protein was found overexpressed in our MPS IIIB cellular model, and its
silencing reduced the hypertrophic response. These results indicate that both c
Src and HB-EGF contribute to the hypertrophic phenotype of NAGLU-depleted
cardiomyoblasts by synergistically activating EGFR and subsequent signaling, thus
suggesting that EGFR pathway inhibition could represent an effective therapeutic
approach for MPS IIIB cardiac disease.
PMID- 29348483
TI - Cell Type-Specific Survey of Epigenetic Modifications by Tandem Chromatin
Immunoprecipitation Sequencing.
AB - The nervous system of higher eukaryotes is composed of numerous types of neurons
and glia that together orchestrate complex neuronal responses. However, this
complex pool of cells typically poses analytical challenges in investigating gene
expression profiles and their epigenetic basis for specific cell types. Here, we
developed a novel method that enables cell type-specific analyses of epigenetic
modifications using tandem chromatin immunoprecipitation sequencing (tChIP-Seq).
FLAG-tagged histone H2B, a constitutive chromatin component, was first expressed
in Camk2a-positive pyramidal cortical neurons and used to purify chromatin in a
cell type-specific manner. Subsequent chromatin immunoprecipitation using
antibodies against H3K4me3-a chromatin modification mainly associated with active
promoters-allowed us to survey the histone modifications in Camk2a-positive
neurons. Indeed, tChIP-Seq identified hundreds of H3K4me3 modifications in
promoter regions located upstream of genes associated with neuronal functions and
genes with unknown functions in cortical neurons. tChIP-Seq provides a versatile
approach to investigating the epigenetic modifications of particular cell types
in vivo.
PMID- 29348484
TI - Activation of Ca2+-sensing receptor as a protective pathway to reduce Cadmium
induced cytotoxicity in renal proximal tubular cells.
AB - Cadmium (Cd), as an extremely toxic metal could accumulate in kidney and induce
renal injury. Previous studies have proved that Cd impact on renal cell
proliferation, autophagy and apoptosis, but the detoxification drugs and the
functional mechanism are still in study. In this study, we used mouse renal
tubular epithelial cells (mRTECs) to clarify Cd-induced toxicity and signaling
pathways. Moreover, we proposed to elucidate the prevent effect of activation of
Ca2+ sensing receptor (CaSR) by Calcimimetic (R-467) on Cd-induced cytotoxicity
and underlying mechanisms. Cd induced intracellular Ca2+ elevation through
phospholipase C-inositol 1, 4, 5-trisphosphate (PLC) followed stimulating p38
mitogen-activated protein kinases (MAPK) activation and suppressing extracellular
signal-regulated kinase (ERK) activation, which leaded to increase apoptotic cell
death and inhibit cell proliferation. Cd induced p38 activation also contribute
to autophagic flux inhibition that aggravated Cd induced apoptosis. R-467
reinstated Cd-induced elevation of intracellular Ca2+ and apoptosis, and it also
increased cell proliferation and restored autophagic flux by switching p38 to ERK
pathway. The identification of the activation of CaSR-mediated protective pathway
in renal cells sheds light on a possible cellular protective mechanism against Cd
induced kidney injury.
PMID- 29348486
TI - Phase I dose-escalation study of copanlisib in combination with gemcitabine or
cisplatin plus gemcitabine in patients with advanced cancer.
AB - BACKGROUND: Copanlisib is a pan-class I phosphatidylinositol 3-kinase (PI3K)
inhibitor with predominant PI3K-alpha/delta activity that has demonstrated
clinical activity and manageable safety when administered as monotherapy in a
phase II study. Combination therapy may overcome compensatory signalling that
could occur with PI3K pathway inhibition, resulting in enhanced inhibitory
activity, and preclinical studies of copanlisib with gemcitabine have
demonstrated potent anti-tumour activity in vivo. METHODS: A phase I, open-label,
dose-escalation study to evaluate the safety, tolerability and recommended phase
II dose (RP2D) of copanlisib with gemcitabine or with cisplatin plus gemcitabine
(CisGem) in patients with advanced malignancies, including an expansion cohort in
patients with biliary tract cancer (BTC) at the RP2D of copanlisib plus CisGem.
Copanlisib and gemcitabine were administered on days 1, 8 and 15 of a 28-day
cycle; maximum tolerated dose (MTD) and RP2D of copanlisib were determined.
Copanlisib plus CisGem was administered on days 1 and 8 of a 21-day cycle;
pharmacokinetics and biomarkers were assessed. RESULTS: Fifty patients received
treatment as follows: dose-escalation cohorts, n=16; copanlisib plus CisGem
cohort, n=14; and BTC expansion cohort, n=20. Copanlisib 0.8 mg kg-1 plus
gemcitabine was the MTD and RP2D for both combinations. Common treatment-emergent
adverse events included nausea (86%), hyperglycaemia (80%) and decreased platelet
count (80%). Copanlisib exposure displayed a dose-proportional increase. No
differences were observed upon co-administration of CisGem. Response rates were
as follows: copanlisib plus gemcitabine, 6.3% (one partial response in a patient
with peritoneal carcinoma); copanlisib plus CisGem, 12% (one complete response
and three partial responses all in patients with BTC (response rate 17.4% in
patients with BTC)). Mutations were detected in PIK3CA (1 out of 43), KRAS (10
out of 43) and BRAF (2 out of 22), with phosphate and tensin homologue protein
loss in 41% (12 out of 29). CONCLUSIONS: Copanlisib plus CisGem demonstrated a
manageable safety profile, favourable pharmacokinetics, and potentially promising
clinical response.
PMID- 29348485
TI - Motor signatures of emotional reactivity in frontotemporal dementia.
AB - Automatic motor mimicry is essential to the normal processing of perceived
emotion, and disrupted automatic imitation might underpin socio-emotional
deficits in neurodegenerative diseases, particularly the frontotemporal
dementias. However, the pathophysiology of emotional reactivity in these diseases
has not been elucidated. We studied facial electromyographic responses during
emotion identification on viewing videos of dynamic facial expressions in 37
patients representing canonical frontotemporal dementia syndromes versus 21
healthy older individuals. Neuroanatomical associations of emotional expression
identification accuracy and facial muscle reactivity were assessed using voxel
based morphometry. Controls showed characteristic profiles of automatic
imitation, and this response predicted correct emotion identification. Automatic
imitation was reduced in the behavioural and right temporal variant groups, while
the normal coupling between imitation and correct identification was lost in the
right temporal and semantic variant groups. Grey matter correlates of emotion
identification and imitation were delineated within a distributed network
including primary visual and motor, prefrontal, insular, anterior temporal and
temporo-occipital junctional areas, with common involvement of supplementary
motor cortex across syndromes. Impaired emotional mimesis may be a core mechanism
of disordered emotional signal understanding and reactivity in frontotemporal
dementia, with implications for the development of novel physiological biomarkers
of socio-emotional dysfunction in these diseases.
PMID- 29348487
TI - H1/pHGFK1 nanoparticles exert anti-tumoural and radiosensitising effects by
inhibition of MET in glioblastoma.
AB - BACKGROUND: The therapeutic resistance to ionising radiation (IR) and anti
angiogenesis mainly impair the prognosis of patients with glioblastoma. The
primary and secondary MET aberrant activation is one crucial factor for these
resistances. The kringle 1 domain of hepatocyte growth factor (HGFK1), an
angiogenic inhibitor, contains a high-affinity binding domain of MET; however,
its effects on glioblastoma remain elusive. METHODS: We formed the nanoparticles
consisting of a folate receptor-targeted nanoparticle-mediated HGFK1 gene
(H1/pHGFK1) and studied its anti-tumoural and radiosensitive activities in both
subcutaneous and orthotopic human glioma cell-xenografted mouse models. We then
elucidated its molecular mechanisms in human glioblastoma cell lines in vitro.
RESULTS: We demonstrated for the first time that peritumoural injection of
H1/pHGFK1 nanoparticles significantly inhibited tumour growth and prolonged
survival in tumour-bearing mice, as well as enhanced the anti-tumoural efficacies
of IR in vivo by reducing Ki-67 expression, enhancing TUNEL staining-indicated
apoptotic indexes, reducing microvascular intensity and reversing IR-induced MET
overexpression in tumour tissues. Furthermore, we showed that HGFK1 suppressed
the proliferation and induced cell apoptosis and enhanced sensitivity to IR in
glioblastoma cell lines, mainly by suppressing the activities of MET receptor,
down-regulating ATM-Chk2 axis but up-regulating Chk1. CONCLUSIONS: H1/pHGFK1
exerts anti-tumoural and radiosensitive activities mainly through the inhibition
and reversal of IR-induced MET and ATM-Chk2 axis activities in glioblastoma.
H1/pHGFK1 nanoparticles are a potential radiosensitiser and angiogenic inhibitor
for glioblastoma treatment.
PMID- 29348488
TI - Interferon-alpha enhances the antitumour activity of EGFR-targeted therapies by
upregulating RIG-I in head and neck squamous cell carcinoma.
AB - BACKGROUND: The epidermal growth factor receptor (EGFR)-targeted therapies have
been tested in the clinic as treatments for head and neck squamous cell carcinoma
(HNSCC). Owing to intrinsic or acquired resistance, EGFR-targeted therapies often
lead to a low response rate and treatment failure. Interferon-alpha (IFNalpha) is
a chemosensitising agent and multi-functional cytokine with a tumour inhibitory
effect. However, the synergic effect of IFNalpha and EGFR-targeted therapies
(erlotinib and nimotuzumab) and their mechanisms in HNSCC remain unclear.
METHODS: The interactions between IFNalpha, erlotinib, and nimotuzumab were
evaluated in vitro in HNSCC cells. The synergistic effect of IFNalpha (20 000 IU
per day, s.c.), erlotinib (50 mg kg-1 per day, i.g.) and nimotuzumab (10 mg kg-1
per day, i.p.) was further confirmed in vivo using HNSCC xenografts in nude mice.
The upregulation of retinoic-acid inducible gene I (RIG-I) induced by IFNalpha
and EGFR-targeted therapies and its mechanism were detected in vitro and in vivo.
RESULTS: IFNalpha enhances the antitumour effects of erlotinib and nimotuzumab on
HNSCC cells both in vitro and in vivo. Importantly, both IFNalpha and EGFR
targeted therapies promote the expression of RIG-I by activating signal
transducers and activators of transcription 1 (STAT1) in HNSCC cells. RIG-I
knockdown reduced the sensitivity of HN4 and HN30 cells to IFNalpha, erlotinib,
and nimotuzumab. Moreover, IFNalpha transcriptionally induced RIG-I expression in
HNSCC cells through STAT1. CONCLUSIONS: IFNalpha enhances the effect of EGFR
targeted therapies by upregulating RIG-I, and its expression may represent a
predictor of the effectiveness of a combination treatment including IFNalpha in
HNSCC.
PMID- 29348489
TI - Which patients are not included in the English Cancer Waiting Times monitoring
dataset, 2009-2013? Implications for use of the data in research.
AB - BACKGROUND: Cancer waiting time targets are routinely monitored in England, but
the Cancer Waiting Times monitoring dataset (CWT) does not include all eligible
patients, introducing scope for bias. METHODS: Data from adults diagnosed in
England (2009-2013) with colorectal, lung, or ovarian cancer were linked from CWT
to cancer registry, mortality, and Hospital Episode Statistics data. We present
demographic characteristics and net survival for patients who were and were not
included in CWT. RESULTS: A CWT record was found for 82% of colorectal, 76% of
lung, and 77% of ovarian cancer patients. Patients not recorded in CWT were more
likely to be in the youngest or oldest age groups, have more comorbidities, have
been diagnosed through emergency presentation, have late or missing stage, and
have much poorer survival. CONCLUSIONS: Researchers and policy-makers should be
aware of the limitations in the completeness and representativeness of CWT, and
draw conclusions with appropriate caution.
PMID- 29348490
TI - Robot-assisted radical prostatectomy vs laparoscopic and open retropubic radical
prostatectomy: functional outcomes 18 months after diagnosis from a national
cohort study in England.
AB - BACKGROUND: Robot-assisted radical prostatectomy (RARP) has been rapidly adopted
without robust evidence comparing its functional outcomes against laparoscopic
radical prostatectomy (LRP) or open retropubic radical prostatectomy (ORP)
approaches. This study compared patient-reported functional outcomes following
RARP, LRP or ORP. METHODS: All men diagnosed with prostate cancer in England
during April - October 2014 who underwent radical prostatectomy were identified
from the National Prostate Cancer Audit and mailed a questionnaire 18 months
after diagnosis. Group differences in patient-reported sexual, urinary, bowel and
hormonal function (EPIC-26 domain scores) and generic health-related quality of
life (HRQoL; EQ-5D-5L scores), with adjustment for patient and tumour
characteristics, were estimated using linear regression. RESULTS: In all, 2219
men (77.0%) responded; 1310 (59.0%) had RARP, 487 (21.9%) LRP and 422 (19.0%)
ORP. RARP was associated with slightly higher adjusted mean EPIC-26 sexual
function scores compared with LRP (3.5 point difference; 95% CI: 1.1-5.9,
P=0.004) or ORP (4.0 point difference; 95% CI: 1.5-6.5, P=0.002), which did not
meet the threshold for a minimal clinically important difference (10-12 points).
There were no significant differences in other EPIC-26 domain scores or HRQoL.
CONCLUSIONS: It is unlikely that the rapid adoption of RARP in the English NHS
has produced substantial improvements in functional outcomes for patients.
PMID- 29348491
TI - Order enables efficient electron-hole separation at an organic heterojunction
with a small energy loss.
AB - Donor-acceptor organic solar cells often show low open-circuit voltages (V OC)
relative to their optical energy gap (E g) that limit power conversion
efficiencies to ~12%. This energy loss is partly attributed to the offset between
E g and that of intermolecular charge transfer (CT) states at the donor-acceptor
interface. Here we study charge generation occurring in PIPCP:PC61BM, a system
with a very low driving energy for initial charge separation (E g-E CT ~ 50 meV)
and a high internal quantum efficiency (eta IQE ~ 80%). We track the strength of
the electric field generated between the separating electron-hole pair by
following the transient electroabsorption optical response, and find that while
localised CT states are formed rapidly (<100 fs) after photoexcitation, free
charges are not generated until 5 ps after photogeneration. In PIPCP:PC61BM,
electronic disorder is low (Urbach energy <27 meV) and we consider that free
charge separation is able to outcompete trap-assisted non-radiative recombination
of the CT state.
PMID- 29348492
TI - v-Src-driven transformation is due to chromosome abnormalities but not Src
mediated growth signaling.
AB - v-Src is the first identified oncogene product and has a strong tyrosine kinase
activity. Much of the literature indicates that v-Src expression induces
anchorage-independent and infinite cell proliferation through continuous
stimulation of growth signaling by v-Src activity. Although all of v-Src
expressing cells are supposed to form transformed colonies, low frequencies of v
Src-induced colony formation have been observed so far. Using cells that exhibit
high expression efficiencies of inducible v-Src, we show that v-Src expression
causes cell-cycle arrest through p21 up-regulation despite ERK activation. v-Src
expression also induces chromosome abnormalities and unexpected suppression of v
Src expression, leading to p21 down-regulation and ERK inactivation. Importantly,
among v-Src-suppressed cells, only a limited number of cells gain the ability to
re-proliferate and form transformed colonies. Our findings provide the first
evidence that v-Src-driven transformation is attributed to chromosome
abnormalities, but not continuous stimulation of growth signaling, possibly
through stochastic genetic alterations.
PMID- 29348493
TI - DNA multi-bit non-volatile memory and bit-shifting operations using addressable
electrode arrays and electric field-induced hybridization.
AB - DNA has been employed to either store digital information or to perform parallel
molecular computing. Relatively unexplored is the ability to combine DNA-based
memory and logical operations in a single platform. Here, we show a DNA tri-level
cell non-volatile memory system capable of parallel random-access writing of
memory and bit shifting operations. A microchip with an array of individually
addressable electrodes was employed to enable random access of the memory cells
using electric fields. Three segments on a DNA template molecule were used to
encode three data bits. Rapid writing of data bits was enabled by electric field
induced hybridization of fluorescently labeled complementary probes and the data
bits were read by fluorescence imaging. We demonstrated the rapid parallel
writing and reading of 8 (23) combinations of 3-bit memory data and bit shifting
operations by electric field-induced strand displacement. Our system may find
potential applications in DNA-based memory and computations.
PMID- 29348494
TI - Diurnal cycle and seasonal variation of cloud cover over the Tibetan Plateau as
determined from Himawari-8 new-generation geostationary satellite data.
AB - Analysis of cloud cover and its diurnal variation over the Tibetan Plateau (TP)
is highly reliant on satellite data; however, the accuracy of cloud detection
from both polar-orbiting and geostationary satellites over this area remains
unclear. The new-generation geostationary Himawari-8 satellites provide high
resolution spatial and temporal information about clouds over the Tibetan
Plateau. In this study, the cloud detection of MODIS and AHI is investigated and
validated against CALIPSO measurements. For AHI and MODIS, the false alarm rate
of AHI and MODIS in cloud identification over the TP was 7.51% and 1.94%,
respectively, and the cloud hit rate was 73.55% and 80.15%, respectively. Using
hourly cloud-cover data from the Himawari-8 satellites, we found that at the
monthly scale, the diurnal cycle in cloud cover over the TP tends to increase
throughout the day, with the minimum and maximum cloud fractions occurring at
10:00 a.m. and 18:00 p.m. local time. Due to the limited time resolution of polar
orbiting satellites, the underestimation of MODIS daytime average cloud cover is
approximately 4.00% at the annual scale, with larger biases during the spring
(5.40%) and winter (5.90%).
PMID- 29348495
TI - Preclinical evaluation of antitumor activity of the proteasome inhibitor MLN2238
(ixazomib) in hepatocellular carcinoma cells.
AB - Hepatocellular carcinoma (HCC) is one of the common malignancies and is an
increasingly important cause of cancer death worldwide. Surgery, chemotherapy,
and radiation therapy extend the 5-year survival limit in HCC patients by only
6%. Therefore, there is a need to develop new therapeutic approaches for the
treatment of this disease. The orally bioavailable proteasome inhibitor MLN2238
(ixazomib) has been demonstrated to have anticancer activity. In the present
study, we investigated the preclinical therapeutic efficacy of MLN2238 in HCC
cells through in vitro and in vivo models, and examined its molecular mechanisms
of action. MLN2238 inhibited cell viability in human HCC cells HepG2, Hep3B, and
SNU475 in a time- and dose-dependent manner. Flow cytometry analysis demonstrated
that MLN2238 induced G2/M cell cycle arrest and cellular apoptosis in HCC cells.
Cell cycle arrest was associated with increased expression levels of p21 and p27.
MLN2238-induced apoptosis was confirmed by caspase-3/7 activation, PARP cleavage
and caspase-dependent beta-catenin degradation. In addition, MLN2238 activated ER
stress genes in HCC cells and increased the expression of the stress-inducible
gene nuclear protein-1. Furthermore, MLN2238 treatment induced upregulation of
myeloid cell leukemia-1 (Mcl-1) protein, and Mcl-1 knockdown sensitized HCC cells
to MLN2238 treatment, suggesting the contribution of Mcl-1 expression to MLN2238
resistance. This result was also confirmed using the novel Mcl-1 small molecule
inhibitor A1210477. Association of A1210477 and MLN2238 determined synergistic
antitumor effects in HCC cells. Finally, in vivo orally administered MLN2238
suppressed tumor growth of Hep3B cells in xenograft models in nude mice. In
conclusion, our results offer hope for a new therapeutic opportunity in the
treatment of HCC patients.
PMID- 29348497
TI - RNA-binding proteins control gene expression and cell fate in the immune system.
AB - RNA-binding proteins (RBPs) are essential for the development and function of the
immune system. They interact dynamically with RNA to control its biogenesis and
turnover by transcription-dependent and transcription-independent mechanisms. In
this Review, we discuss the molecular mechanisms by which RBPs allow gene
expression changes to occur at different speeds and to varying degrees, and which
RBPs regulate the diversity of the transcriptome and proteome. These proteins are
nodes for integration of transcriptional and signaling networks and are
intimately linked to intermediary metabolism. They are essential components of
regulatory feedback mechanisms that maintain immune tolerance and limit
inflammation. The role of RBPs in malignancy and autoimmunity has led to their
emergence as targets for the development of new therapeutic modalities.
PMID- 29348498
TI - mTECs Aire on the side of caution.
PMID- 29348496
TI - Natriuretic peptides promote glucose uptake in a cGMP-dependent manner in human
adipocytes.
AB - Robust associations between low plasma level of natriuretic peptides (NP) and
increased risk of type 2 diabetes (T2D) have been recently reported in humans.
Adipose tissue (AT) is a known target of NP. However it is unknown whether NP
signalling in human AT relates to insulin sensitivity and modulates glucose
metabolism. We here show in two European cohorts that the NP receptor guanylyl
cyclase-A (GC-A) expression in subcutaneous AT was down-regulated as a function
of obesity grade while adipose NP clearance receptor (NPRC) was up-regulated.
Adipose GC-A mRNA level was down-regulated in prediabetes and T2D, and negatively
correlated with HOMA-IR and fasting blood glucose. We show for the first time
that NP promote glucose uptake in a dose-dependent manner. This effect is reduced
in adipocytes of obese individuals. NP activate mammalian target of rapamycin
complex 1/2 (mTORC1/2) and Akt signalling. These effects were totally abrogated
by inhibition of cGMP-dependent protein kinase and mTORC1/2 by rapamycin. We
further show that NP treatment favoured glucose oxidation and de novo lipogenesis
independently of significant gene regulation. Collectively, our data support a
role for NP in blood glucose control and insulin sensitivity by increasing
glucose uptake in human adipocytes. This effect is partly blunted in obesity.
PMID- 29348499
TI - ERAdP standing in the shadow of STING innate immune signaling.
PMID- 29348502
TI - Stress-induced depression.
PMID- 29348501
TI - Myocardial infarct inflammation.
PMID- 29348503
TI - NKT cells aid antiviral responses.
PMID- 29348500
TI - Myeloid-derived suppressor cells coming of age.
AB - Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells
generated during a large array of pathologic conditions ranging from cancer to
obesity. These cells represent a pathologic state of activation of monocytes and
relatively immature neutrophils. MDSCs are characterized by a distinct set of
genomic and biochemical features, and can, on the basis of recent findings, be
distinguished by specific surface molecules. The salient feature of these cells
is their ability to inhibit T cell function and thus contribute to the
pathogenesis of various diseases. In this Review, we discuss the origin and
nature of these cells; their distinctive features; and their biological roles in
cancer, infectious diseases, autoimmunity, obesity and pregnancy.
PMID- 29348504
TI - Trials and Tribble-ations of tissue TRM cells.
PMID- 29348505
TI - Antibiotics-immune system interactions.
PMID- 29348506
TI - Macrophages: damage control.
PMID- 29348507
TI - Stressed-out ROS take a silent death route.
PMID- 29348508
TI - Adipose tissue TM cells.
PMID- 29348509
TI - Triggering molecular assembly at the mesoscale for advanced Raman detection of
proteins in liquid.
AB - An advanced optofluidic system for protein detection based on Raman signal
amplification via dewetting and molecular gathering within temporary mesoscale
assemblies is presented. The evaporation of a microliter volume of protein
solution deposited in a circular microwell precisely follows an outward-receding
geometry. Herein the combination of liquid withdrawal with intermolecular
interactions induces the formation of self-assembled molecular domains at the
solid-liquid interface. Through proper control of the evaporation rate, amplitude
of the assemblies and time for spectral collection at the liquid edge are
extensively raised, resulting in a local enhancement and refinement of the Raman
response, respectively. Further signal amplification is obtained by taking
advantage of the intense local electromagnetic fields generated upon adding a
plasmonic coating to the microwell. Major advantages of this optofluidic method
lie in the obtainment of high-quality, high-sensitivity Raman spectra with
detection limit down to sub-micromolar values. Peculiarly, the assembled proteins
in the liquid edge region maintain their native-like state without displaying
spectral changes usually occurring when dried drop deposits are considered.
PMID- 29348510
TI - Genome and secretome analysis of Pochonia chlamydosporia provide new insight into
egg-parasitic mechanisms.
AB - Pochonia chlamydosporia infects eggs and females of economically important plant
parasitic nematodes. The fungal isolates parasitizing different nematodes are
genetically distinct. To understand their intraspecific genetic differentiation,
parasitic mechanisms, and adaptive evolution, we assembled seven putative
chromosomes of P. chlamydosporia strain 170 isolated from root-knot nematode eggs
(~44 Mb, including 7.19% of transposable elements) and compared them with the
genome of the strain 123 (~41 Mb) isolated from cereal cyst nematode. We focus on
secretomes of the fungus, which play important roles in pathogenicity and fungus
host/environment interactions, and identified 1,750 secreted proteins, with a
high proportion of carboxypeptidases, subtilisins, and chitinases. We analyzed
the phylogenies of these genes and predicted new pathogenic molecules. By
comparative transcriptome analysis, we found that secreted proteins involved in
responses to nutrient stress are mainly comprised of proteases and glycoside
hydrolases. Moreover, 32 secreted proteins undergoing positive selection and 71
duplicated gene pairs encoding secreted proteins are identified. Two duplicated
pairs encoding secreted glycosyl hydrolases (GH30), which may be related to
fungal endophytic process and lost in many insect-pathogenic fungi but exist in
nematophagous fungi, are putatively acquired from bacteria by horizontal gene
transfer. The results help understanding genetic origins and evolution of
parasitism-related genes.
PMID- 29348511
TI - Resonant plasma excitation by single-cycle THz pulses.
AB - In this paper, an alternative perspective for the generation of millimetric high
gradient resonant plasma waves is discussed. This method is based on the plasma
wave excitation by energetic single-cycle THz pulses whose temporal length is
comparable to the plasma wavelength. The excitation regime discussed in this
paper is the quasi-nonlinear regime that can be achieved when the normalized
vector potential of the driving THz pulse is on the order of unity. To
investigate this regime and determine the strength of the excited electric
fields, a Particle-In-Cell (PIC) code has been used. It has been found that by
exploiting THz pulses with characteristics currently available in laboratory,
longitudinal electron plasma waves with electric gradients up to hundreds MV/m
can be obtained. The mm-size nature of the resonant plasma wave can be of great
utility for an acceleration scheme in which high-brightness electron bunches are
injected into the wave to undergo a strong acceleration. The long-size nature of
the acceleration bucket with respect to the short length of the electron bunches
can be handled in a more robust manner in comparison with the case when
micrometric waves are employed.
PMID- 29348513
TI - Publisher Correction: Functionalized Non-vascular Nitinol Stent via
Electropolymerized Polydopamine Thin Film Coating Loaded with Bortezomib Adjunct
to Hyperthermia Therapy.
AB - A correction to this article has been published and is linked from the HTML
version of this paper. The error has been fixed in the paper.
PMID- 29348512
TI - CA1 and CA3 differentially support spontaneous retrieval of episodic contexts
within human hippocampal subfields.
AB - The hippocampus plays a critical role in spatial and episodic memory. Mechanistic
models predict that hippocampal subfields have computational specializations that
differentially support memory. However, there is little empirical evidence
suggesting differences between the subfields, particularly in humans. To clarify
how hippocampal subfields support human spatial and episodic memory, we developed
a virtual reality paradigm where participants passively navigated through houses
(spatial contexts) across a series of videos (episodic contexts). We then used
multivariate analyses of high-resolution fMRI data to identify neural
representations of contextual information during recollection. Multi-voxel
pattern similarity analyses revealed that CA1 represented objects that shared an
episodic context as more similar than those from different episodic contexts.
CA23DG showed the opposite pattern, differentiating between objects encountered
in the same episodic context. The complementary characteristics of these
subfields explain how we can parse our experiences into cohesive episodes while
retaining the specific details that support vivid recollection.
PMID- 29348514
TI - 3D Imaging through Scatterers with Interferenceless Optical System.
AB - Imaging through a scattering medium is a challenging task. We propose and
demonstrate an interferenceless incoherent opto-digital technique for 3D imaging
through a scatterer with a single lens and a digital camera. The light diffracted
from a point object is modulated by a scattering mask. The modulated wavefront is
projected on an image sensor using a spherical lens and the impulse response is
recorded. An object is placed at the same axial location as the point object and
another intensity pattern is recorded with identical experimental conditions and
with the same scattering mask. The image of the object is reconstructed by a
cross-correlation between a reconstructing function and the object hologram. For
3D imaging, a library of reconstructing functions are created corresponding to
different axial locations. The different planes of the object are reconstructed
by a cross-correlation of the object hologram with the corresponding
reconstructing functions.
PMID- 29348516
TI - Evidence of the Zanclean megaflood in the eastern Mediterranean Basin.
AB - The Messinian salinity crisis (MSC) - the most abrupt, global-scale environmental
change since the end of the Cretaceous - is widely associated with partial
desiccation of the Mediterranean Sea. A major open question is the way normal
marine conditions were abruptly restored at the end of the MSC. Here we use
geological and geophysical data to identify an extensive, buried and chaotic
sedimentary body deposited in the western Ionian Basin after the massive
Messinian salts and before the Plio-Quaternary open-marine sedimentary sequence.
We show that this body is consistent with the passage of a megaflood from the
western to the eastern Mediterranean Sea via a south-eastern Sicilian gateway.
Our findings provide evidence for a large amplitude drawdown in the Ionian Basin
during the MSC, support the scenario of a Mediterranean-wide catastrophic flood
at the end of the MSC, and suggest that the identified sedimentary body is the
largest known megaflood deposit on Earth.
PMID- 29348515
TI - Genetic evidence for panmixia in a colony-breeding crater lake cichlid fish.
AB - Fine-scaled genetic structuring, as seen for example in many lacustrine fish,
typically relates to the patterns of migration, habitat use, mating system or
other ecological factors. Because the same processes can also affect the
propensity of population differentiation and divergence, assessments of species
from rapidly speciating clades, or with particularly interesting ecological
traits, can be especially insightful. For this study, we assessed the spatial
genetic relationships, including the genetic evidence for sex-biased dispersal,
in a colony-breeding cichlid fish, Amphilophus astorquii, endemic to Crater Lake
Apoyo in Nicaragua, using 11 polymorphic microsatellite loci (n = 123 individuals
from three colonies). We found no population structure in A. astorquii either
within colonies (no spatial genetic autocorrelation, r ~0), or at the lake-wide
level (pairwise population differentiation FST = 0-0.013 and no clustering), and
there was no sex-bias (male and female AIc values bounded 0) to this lack of
genetic structure. These patterns may be driven by the colony-breeding
reproductive behaviour of A. astorquii. The results suggest that strong
philopatry or spatial assortative mating are unlikely to explain the rapid
speciation processes associated with the history of this species in Lake Apoyo.
PMID- 29348517
TI - NDRG2 contributes to cisplatin sensitivity through modulation of BAK-to-Mcl-1
ratio.
AB - The downregulation of N-Myc downstream-regulated gene 2 (NDRG2) is known to be
associated with the progression and poor prognosis of several cancers.
Sensitivity to anti-cancer may be associated with a good prognosis in cancer
patients, and NDRG2, which is induced by p53, sensitizes the cells to
chemotherapy. However, the unique function of NDRG2 as an inducer of apoptosis
under chemotreatment has not been sufficiently studied. In this study, we
investigated the role of NDRG2 in chemo-sensitivity, focusing on cisplatin in
U937 histiocytic lymphoma, which has the loss-of-functional mutation in p53.
NDRG2 promoted the sensitivity to cisplatin through the modulation of the BAK-to
Mcl-1 ratio. The degradation of Mcl-1 and increase in BAK were mediated by JNK
activation and the eIF2alpha/p-eIF2alpha pathway, respectively, which depended on
PKR activation in NDRG2-overexpressed U937 (U937-NDRG2) cells. NOX5 was highly
expressed in U937-NDRG2 cells and contributed to ROS production after cisplatin
treatment. ROS scavenging or NOX5-knockdown successfully inhibited the
sensitivity of U937-NDRG2 cells to cisplatin. Taken together, these findings
indicate that NDRG2 contributed to the increased sensitivity to ciplatin through
the modulation of Bak-to-Mcl-1 ratio regulated by NOX5-ROS-PKR pathway;
therefore, we suggest that NDRG2 may be a molecular target for improving the
efficacy of drug treatment in cancer patients.
PMID- 29348518
TI - Serum omega-3 Polyunsaturated Fatty Acids and Potential Influence Factors in
Elderly Patients with Multiple Cardiovascular Risk Factors.
AB - Recent clinical trials failed to demonstrate that omega-3 polyunsaturated fatty
acid (PUFA) supplement reduced cardiovascular events, which contradicted previous
evidence. However, serum omega-3 PUFA concentrations of participants remained
unclear in those studies. We aimed to investigate the definite relationship
between serum concentrations of omega-3 PUFAs and coronary artery disease (CAD),
and to explore the potential influence factors of omega-3 PUFAs. We selected
Chinese in-patients (n = 460) with multiple cardiovascular risk factors or an
established diagnosis of CAD. Serum omega-3 PUFAs, including eicosapentaenoic
acid (EPA) and docosahexaenoic acid (DHA), were measured by liquid chromatography
mass spectrometry. Serum concentrations of omega-3 PUFAs in CAD patients were
lower than that in patients with cardiovascular risk factors. Furthermore, high
serum DHA concentration was an independent protective factor of CAD after
adjustment for confounding factors (OR: 0.52, p = 0.014). Alcohol intake (p =
0.036) and proton pump inhibitor (PPI) usage (p = 0.027) were associated with a
decreased serum omega-3 PUFA concentration. We conclude that serum concentrations
of omega-3 PUFAs may associate with a decreased CAD proportion, and DHA may serve
as a protective factor of CAD. Serum omega-3 PUFA concentrations may be reduced
by alcohol intake and certain drugs like PPIs.
PMID- 29348520
TI - Discharge without alarm(s)!
PMID- 29348519
TI - Guanylate Binding Protein 1 Inhibits Osteogenic Differentiation of Human
Mesenchymal Stromal Cells Derived from Bone Marrow.
AB - Guanylate Binding Proteins (GBPs) are a group of cytokine-inducible large
guanosine triphosphatase. Previous studies have shown high expression of GBP1 in
circulating monocytes of premenopausal subjects was correlated to extremely low
peak bone mass, which is considered as an important determinant of osteoporosis.
However, whether GBPs play a role in regulation of osteogenesis of mesenchymal
stromal cells (MSCs) remains largely unknown. In the present study, we found that
mRNA expression of GBP1 was highest among all the GBPs, and it was dramatically
downregulated during osteogenic differentiation of human MSCs derived from bone
marrow (hBM-MSCs). While siRNA-mediated knockdown of GBP1 promoted osteogenesis,
overexpression of GBP1 suppressed osteogenesis of hBM-MSCs. Furthermore, we found
GBP1 is required for expression of indoleamine 2,3 dioxygenase (IDO), Interleukin
6 (IL-6) and IL-8 induced by treatment with Interferon-gamma (IFN-gamma).
Depletion of GBP1 rescued the inhibited osteogenesis induced by IFN-gamma
treatment, at least in part. Collectively, our findings indicate GBP1 inhibits
osteogenic differentiation of MSCs, and inhibition of GBP1 expression may prevent
development of osteoporosis and facilitate MSC-based bone regeneration.
PMID- 29348521
TI - JBIR-150, a novel 20-membered polyene macrolactam from marine-derived
Streptomyces sp. OPMA00071.
AB - During the course of constructing a natural product library for drug screening
consisting of microbial culture extracts originated from marine samples, we
evaluated natural product components profiles via UPLC TOF-MS and routine
biological tests for cytotoxic and antibiotic activities for all of the culture
extract samples. By combination of chemical screening and biological activities,
we succeeded in discovering a 20-membered macrolactam antibiotic subsequently
designated JBIR-150 (1) from a marine-derived actinomycete identified as
Streptomyces sp. that was isolated from an Okinawan marine sediment. The chemical
structure of 1 was determined by interpreting NMR spectroscopic and mass
spectrometric data. Compound 1 exhibited moderate cytotoxicity against MESO-1 and
Jurkat cells.
PMID- 29348522
TI - In vitro and in vivo antimicrobial activity of TS2037, a novel aminoglycoside
antibiotic.
AB - To overcome serious methicillin-resistant Staphylococcus aureus (MRSA) and
Pseudomonas aeruginosa infections, we synthesized TS2037, 5,4"-diepi-arbekacin, a
novel aminoglycoside antibiotic, and evaluated its biological properties. TS2037
showed broad-range, as well as robust antibacterial activities against Gram
positive and Gram-negative bacteria. The MIC50 and MIC90 of TS2037 against
clinical isolates of MRSA (n = 54) were both 0.25 ug/mL, and no resistant strain
was observed. The MIC50 and MIC90 of TS2037 against clinical isolates of P.
aeruginosa (n = 54) were 1 and 4 ug/mL, respectively. TS2037 and arbekacin, anti
MRSA aminoglycoside, were more stable against AAC(6')-APH(2"), aminoglycoside-6'
N-acetyltransferase and 2"-O-phosphotransferase, produced by resistant S. aureus
than gentamicin. Therapeutic efficacies of TS2037 in the mouse models of systemic
infection with MRSA were superior to those of arbekacin, vancomycin, and
linezolid. The efficacy of TS2037 against systemic infection caused by P.
aeruginosa producing AAC(6')-II was superior to those of arbekacin and amikacin.
In the nephrotoxicity risk screening, the release of free N-acetyl-beta-D
glucosaminidase from the kidney epithelial cell line after treatment with TS2037
at 2.5 and 5.0 MUM were 2.0 and 2.1 (U/L), respectively, which were about two
times higher than those of arbekacin. In conclusion, TS2037 exhibited the most
potent antibacterial activity among aminoglycosides tested against both MRSA and
P. aeruginosa in vitro and in vivo, although its nephrotoxicity risk remains to
be improved.
PMID- 29348523
TI - Antibiotic resistance mutations induced in growing cells of Bacillus-related
thermophiles.
AB - Stress-induced mutagenesis can assist pathogens in generating drug-resistant
cells during antibiotic therapy; however, if and how antibiotics induce
mutagenesis in microbes remains poorly understood. A non-pathogenic thermophile,
Geobacillus kaustophilus HTA426, efficiently produces derivative cells resistant
to rifampicin and streptomycin via rpoB and rpsL mutations, respectively. Here,
we examined this phenomenon to suggest a novel mutagenic mode induced by
antibiotics. Fluctuation analysis indicated that mutations occurred via
spontaneous mutations during culture. However, mutations were much more frequent
in growing cells than stationary cells, and mutation sites were varied through
cell growth. These observations suggested that growing cells induced mutagenesis
in response to antibiotics. An in-frame deletion of mfd, which governs
transcription-coupled repair to correct DNA lesions on the transcribed strand,
caused mutations that were comparable between growing and stationary cells;
therefore, the mutagenic mechanism was attributable to DNA repair defects where
growing cells depressed mfd function. Mutations occurred more frequently at
optimal growth temperatures for G. kaustophilus than at a higher growth
temperature, suggesting that the mutagenesis relies on active cellular activities
rather than high temperature-associated DNA damage. In addition, the mutagenesis
may involve a mutagenic factor targeting these sites, in addition to mfd
depression, because rpoB and rpsL mutations were dominant at thymine and guanine
sites on the transcribed strand. A similar mutagenic profile was observed for
other Geobacillus and thermophilic Bacillus species. This suggests that Bacillus
related thermophiles commonly induce mutagenesis in response to rifampicin and
streptomycin to produce resistant cells.
PMID- 29348524
TI - Linearmycins are lytic membrane-targeting antibiotics.
AB - The linearmycin family of polyketides was originally classified as antifungal
metabolites. However, in addition to antifungal activity, we previously found
that linearmycins cause cellular lysis and colony degradation of the Gram
positive bacterium Bacillus subtilis. We recently showed that Streptomyces sp.
strain Mg1 incorporates linearmycins into extracellular vesicles, which are
capable of lysing B. subtilis. However, the mechanism of linearmycin-induced
lysis was hitherto unexplored. Therefore, we sought to determine how linearmycin
laden vesicles cause lysis. In this study, we found that linearmycins inhibited
the growth of all Gram-positive bacteria that we tested, but lysis was limited to
some Bacillus species. Next, we found that linearmycin-induced lysis occurred
even when cellular metabolism and growth were inhibited, which suggested that
linearmycins possess the intrinsic capacity to lyse cells, unlike cell-wall
targeting antibiotics. We showed that linearmycin exposure caused changes
consistent with rapid depolarization of the B. subtilis cytoplasmic membrane,
which was correlated with a loss of viability. Finally, using liposomes as in
vitro membrane models, we demonstrated that linearmycins are capable of
disrupting lipid bilayers without any other cellular components. Taken together,
our results strongly indicate that the cytoplasmic membrane is the direct
antibacterial target of linearmycins.
PMID- 29348525
TI - Cordybislactone, a stereoisomer of the 14-membered bislactone clonostachydiol,
from the hopper pathogenic fungus Cordyceps sp. BCC 49294: revision of the
absolute configuration of clonostachydiol.
AB - Cordybislactone (3), a new stereoisomer of the 14-membered bislactone
clonostachydiol, together with its open ring analog (4), was isolated from the
hopper pathogenic fungus Cordyceps sp. BCC 49294. The relative and absolute
configurations of 3 were determined by chemical derivatizations, including the
modified Mosher's method. The stereochemistry of clonostachydiol was determined
using the natural compound isolated from Xylaria sp. BCC 4297. The result
revealed that the absolute configuration of clonostachydiol, previously
determined by synthesis, should be revised to its enantiomer.
PMID- 29348526
TI - Prodigiosin R2, a new prodigiosin from the roseophilin producer Streptomyces
griseoviridis 2464-S5.
AB - Roseophilin (2) is a unique prodigiosin-related compound produced by Streptomyces
griseoviridis 2464-S5, and is characterized by a central furan ring and a
bicyclic alkyl chain. During a search for biosynthetic intermediates of 2, a new
metabolite designated prodigiosin R2 (1) was isolated from the culture of the
roseophilin producer. The molecular formula of 1 was established as C27H35N3O by
high-resolution FAB-MS. The structure of 1 was determined by NMR spectroscopic
analyses as a prodigiosin derivative with the same bicyclic alkyl chain as 2.
Prodigiosin R2 (1) showed potent cytotoxicity against HeLa human cervical
carcinoma cells and HT1080 human fibrosarcoma cells with IC50s of 0.41 and 0.82
MUM, respectively.
PMID- 29348527
TI - The human muscarinic acetylcholine receptor antagonist, Dicyclomine targets
signal transduction genes and inhibits the virulence factors in the human
pathogen, Candida albicans.
AB - Dicyclomine is a human muscarinic acetylcholine receptor antagonist used for the
treatment of abdominal cramps. We are reporting here that dicyclomine can inhibit
the in vitro growth and virulence factors of the human pathogen Candida albicans
very effectively. Dicyclomine inhibited adhesion, early biofilm, mature biofilm,
and planktonic growth. Yeast to hyphal form transition of C. albicans in various
inducer media such as serum, proline, glucose, and N-acetylglucosamine was
inhibited. Dicyclomine also could kill C. albicans cells within 15 min of
exposure. Dicyclomine appears to inhibit the yeast to hyphal conversion by
affecting signal transduction pathway. The expression of selected genes
associated with yeast to hyphal form transition in serum in presence of
dicyclomine was studied using real-time polymerase chain reaction (RtPCR). The
RtPCR analysis showed that dicyclomine targets both cAMP pathway as well as MAPK
cascade. Eight genes were upregulated. Out of these, three major upregulated
genes were Bcy1, Tup1, and Mig1. Dicyclomine downregulated Ume6, Ece1, and Pde2
genes which are involved in cAMP signaling pathway and also downregulated the DNA
binding protein gene, Rfg1. Dicyclomine significantly upregulated the master
negative regulator of hyphal formation, Tup1. Based on this study we suggest that
the muscarinic acetylcholine receptor antagonist, dicyclomine could be
repositioned as a potential anti-Candida albicans as well as anti-virulence
agent.
PMID- 29348528
TI - Agrocin 108 is a 5'-cytidine nucleotide bacteriocin containing a carbocyclic
phosphoryl-ascorbate group.
AB - Agrocin 108 is a 3'-O-beta-D-xylopyranosyl-cytidine-5'-O-phosphodiester of an
ascorbate-carbocyclic cyclopentenone analogue, with bacteriocin-like properties.
This bacteriocin exhibits orders of magnitude greater than the inhibition zone
diameter towards the indicator strain than either ampicillin or streptomycin. It
has been isolated from cultures of Rhizobium rhizogenes strain K108. The
structure of the agrocin 108 without detail, has been previously published. We
now report a detailed structure elucidation, including the hitherto undetermined
residual 5'-phospho-diester fragment by a combination of 1D and 2D NMR studies at
various pH values in H2O/D2O, high resolution MS, pKa determination, and chemical
degradation.
PMID- 29348529
TI - Two new lankacidin-related metabolites from Streptomyces sp. HS-NF-1178.
AB - Two new lankacidin-related metabolites, 2,18-seco-lankacidinol A (1), 2,18-seco
lankacidinol B (2) and a known compound, lankacidinol (3), were isolated from the
fermentation broth of Streptomyces sp. HS-NF-1178. Their structures were
determined on the basis of spectroscopic analysis, including 1D and 2D NMR
techniques as well as ESI-MS and comparison with data from the literature. These
two new compounds, especially compound 1, exhibited potent antitumor activity.
PMID- 29348530
TI - Time inside the mutant selection window as a predictor of staphylococcal
resistance to linezolid.
AB - To explore if the time inside the mutant selection window (TMSW) is a reliable
predictor of emergence of bacterial resistance to linezolid, mixed inocula of
each of three methicillin-resistant Staphylococcus aureus strains (MIC of
linezolid 2 MUg ml-1) and their previously selected resistant mutants (MIC 8 MUg
ml-1) were exposed to linezolid pharmacokinetics using an in vitro dynamic model.
In five-day treatments simulated over a wide range of the 24-h area under the
concentration-time curve (AUC24) to the MIC ratio, mutants resistant to 4 * MIC
of antibiotic were enriched in a TMSW-dependent manner. With each strain, TMSW
relationships with the area under the bacterial mutant concentration-time curve
(AUBCM) exhibited a hysteresis loop, with the upper portion corresponding to the
time above the mutant prevention concentration (MPC; T>MPC) of 0 and the lower
portion-to the T>MPC > 0. Using AUBCM related to the maximal value observed with
a given strain (normalized AUBCM) at T>MPC > 0, a strain-independent sigmoid
relationship was established between AUBCM and TMSW, as well as T>MPC (r2 0.99
for both). AUC24/MIC and AUC24/MPC relationships with normalized AUBCM for
combined data on the three studied S. aureus strains were bell-shaped (r2 0.85
and 0.80, respectively). These findings suggest that TMSW at T>MPC > 0, T>MPC,
AUC24/MIC and AUC24/MPC are useful bacterial strain-independent predictors of the
emergence of staphylococcal resistance to linezolid.
PMID- 29348531
TI - Isopentylated diphenyl ether derivatives from the fermentation products of an
endophytic fungus Phomopsis fukushii.
AB - Three new isopentylated diphenyl ethers, (1-3), together with two known
isopentylated diphenyl ethers derivatives (4 and 5) were isolated from the
fermentation products of an endophytic fungus Phomopsis fukushii. Their
structures were elucidated by spectroscopic methods, including extensive 1D- and
2D NMR techniques. Compounds 1-3 were evaluated for their anti-methicillin
resistant Staphylococcus aureus (anti-MRSA) activity. The results showed that
compounds 1-3 showed strong activity with diameter of inhibition zone (IZD) of
21.8 +/- 2.4 mm, 16.8 +/- 2.2 mm, and 15.6 +/- 2.0 mm, respectively.
PMID- 29348533
TI - Structured thermal surface for radiative camouflage.
AB - Thermal camouflage has been successful in the conductive regime, where thermal
metamaterials embedded in a conductive system can manipulate heat conduction
inside the bulk. Most reported approaches are background-dependent and not
applicable to radiative heat emitted from the surface of the system. A coating
with engineered emissivity is one option for radiative camouflage, but only when
the background has uniform temperature. Here, we propose a strategy for radiative
camouflage of external objects on a given background using a structured thermal
surface. The device is non-invasive and restores arbitrary background temperature
distributions on its top. For many practical candidates of the background
material with similar emissivity as the device, the object can thereby be
radiatively concealed without a priori knowledge of the host conductivity and
temperature. We expect this strategy to meet the demands of anti-detection and
thermal radiation manipulation in complex unknown environments and to inspire
developments in phononic and photonic thermotronics.
PMID- 29348532
TI - Amygdala-orbitofrontal structural and functional connectivity in females with
anxiety disorders, with and without a history of conduct disorder.
AB - Conduct disorder (CD) and anxiety disorders (ADs) are often comorbid and both are
characterized by hyper-sensitivity to threat, and reduced structural and
functional connectivity between the amygdala and orbitofrontal cortex (OFC).
Previous studies of CD have not taken account of ADs nor directly compared
connectivity in the two disorders. We examined three groups of young women: 23
presenting CD and lifetime AD; 30 presenting lifetime AD and not CD; and 17 with
neither disorder (ND). Participants completed clinical assessments and diffusion
weighted and resting-state functional MRI scans. The uncinate fasciculus was
reconstructed using tractography and manual dissection, and structural measures
extracted. Correlations of resting-state activity between amygdala and OFC seeds
were computed. The CD + AD and AD groups showed similarly reduced structural
integrity of the left uncinate compared to ND, even after adjusting for IQ,
psychiatric comorbidity, and childhood maltreatment. Uncinate integrity was
associated with harm avoidance traits among AD-only women, and with the
interaction of poor anger control and anxiety symptoms among CD + AD women.
Groups did not differ in functional connectivity. Reduced uncinate integrity
observed in CD + AD and AD-only women may reflect deficient emotion regulation in
response to threat, common to both disorders, while other neural mechanisms
determine the behavioral response.
PMID- 29348534
TI - Anti-cancer activities of allyl isothiocyanate and its conjugated silicon quantum
dots.
AB - Allyl isothiocyanate (AITC), a dietary phytochemical in some cruciferous
vegetables, exhibits promising anticancer activities in many cancer models.
However, previous data showed AITC to have a biphasic effect on cell viability,
DNA damage and migration in human hepatoma HepG2 cells. Moreover, in a 3D co
culture of HUVEC with pericytes, it inhibited tube formation at high doses but
promoted this at low doses, which confirmed its biphasic effect on angiogenesis.
siRNA knockdown of Nrf2 and glutathione inhibition abolished the stimulation
effect of AITC on cell migration and DNA damage. The biological activity of a
novel AITC-conjugated silicon quantum dots (AITC-SiQDs) has been investigated for
the first time. AITC-SiQDs showed similar anti-cancer properties to AITC at high
doses while avoiding the low doses stimulation effect. In addition, AITC-SiQDs
showed a lower and long-lasting activation of Nrf2 translocation into nucleus
which correlated with their levels of cellular uptake, as detected by the
intrinsic fluorescence of SiQDs. ROS production could be one of the mechanisms
behind the anti-cancer effect of AITC-SiQDs. These data provide novel insights
into the biphasic effect of AITC and highlight the application of nanotechnology
to optimize the therapeutic potential of dietary isothiocyanates in cancer
treatment.
PMID- 29348535
TI - Umbilical cord extracts improve osteoporotic abnormalities of bone marrow-derived
mesenchymal stem cells and promote their therapeutic effects on ovariectomised
rats.
AB - Bone marrow-derived mesenchymal stem cells (BM-MSCs) are the most valuable source
of autologous cells for transplantation and tissue regeneration to treat
osteoporosis. Although BM-MSCs are the primary cells responsible for maintaining
bone metabolism and homeostasis, their regenerative ability may be attenuated in
postmenopausal osteoporosis patients. Therefore, we first examined potential
abnormalities of BM-MSCs in an oestrogen-deficient rat model constructed by
ovariectomy (OVX-MSCs). Cell proliferation, mobilisation, and regulation of
osteoclasts were downregulated in OVX-MSCs. Moreover, therapeutic effects of OVX
MSCs were decreased in OVX rats. Accordingly, we developed a new activator for BM
MSCs using human umbilical cord extracts, Wharton's jelly extract supernatant
(WJS), which improved cell proliferation, mobilisation and suppressive effects on
activated osteoclasts in OVX-MSCs. Bone volume, RANK and TRACP expression of
osteoclasts, as well as proinflammatory cytokine expression in bone tissues, were
ameliorated by OVX-MSCs activated with WJS (OVX-MSCs-WJ) in OVX rats. Fusion and
bone resorption activity of osteoclasts were suppressed in macrophage-induced and
primary mouse bone marrow cell-induced osteoclasts via suppression of osteoclast
specific genes, such as Nfatc1, Clcn7, Atp6i and Dc-stamp, by co-culture with OVX
MSCs-WJ in vitro. In this study, we developed a new activator, WJS, which
improved the functional abnormalities and therapeutic effects of BM-MSCs on
postmenopausal osteoporosis.
PMID- 29348536
TI - Surround inhibition can instantly be modulated by changing the attentional focus.
AB - To further investigate the mechanism of surround inhibition (SI) and to determine
whether adopting different attentional strategies might have an impact on the
modulation of SI, the effects of adopting an external (EF) or internal focus of
attention (IF) on SI and motor performance were investigated. While performing an
index flexion with either an EF or IF, transcranial magnetic stimulation was
applied at various time points in 14 healthy subjects. When adopting an EF
compared to an IF, the results show an improved motor performance (+14.7% in MVC)
and a reduced bEMG in the adjacent APB (-22.3%) during maximal index flexion.
This was accompanied by an increased SI in the APB with an EF (+26.4%).
Additionally, the decrease in bEMG correlated with the magnitude of SI in APB.
The current results demonstrate an efficient way to modulate SI by changing the
attentional focus in healthy subjects and might, at least in part, explain the
better motor performance being associated with an EF. The present findings help
to better understand the positive mechanisms of an EF on SI in the healthy motor
system and may also points towards a treatment strategy in pathologies with
disturbed SI such as focal hand dystonia.
PMID- 29348538
TI - Broadband wave plates made by plasmonic metamaterials.
AB - Although metamaterials wave-plates have been demonstrated previously, many of
them suffer from the issue of narrow bandwidth since they typically rely on
resonance principles and thus exhibit inevitable frequency dispersions. Here, we
show that the dispersion of spoof surface plasmon (SSP) mode supported by a
fishbone structure can be freely modulated by varying the structural parameters.
This motivates us to establish a general strategy of building broadband wave
plates by cascading two fishbone structures with different propagation constants
of SSP modes. We derive a criterion under which the cross-polarization phase
difference across the whole device can maintain at a nearly constant value over a
wide frequency band, with frequency dispersions in the two fishbone structures
cancelled out. As an illustration, we design and fabricate an efficient microwave
quarter-wave plate and experimentally characterize its excellent polarization
control performances over a broad frequency band (7-9.2 GHz). Our findings can
stimulate making dispersion-controlled high-performance optical functional
devices in different frequency domains.
PMID- 29348537
TI - Radionuclides transform chemotherapeutics into phototherapeutics for precise
treatment of disseminated cancer.
AB - Most cancer patients succumb to disseminated disease because conventional
systemic therapies lack spatiotemporal control of their toxic effects in vivo,
particularly in a complicated milieu such as bone marrow where progenitor stem
cells reside. Here, we demonstrate the treatment of disseminated cancer by
photoactivatable drugs using radiopharmaceuticals. An orthogonal-targeting
strategy and a contact-facilitated nanomicelle technology enabled highly
selective delivery and co-localization of titanocene and radiolabelled
fluorodeoxyglucose in disseminated multiple myeloma cells. Selective ablation of
the cancer cells was achieved without significant off-target toxicity to the
resident stem cells. Genomic, proteomic and multimodal imaging analyses revealed
that the downregulation of CD49d, one of the dimeric protein targets of the
nanomicelles, caused therapy resistance in small clusters of cancer cells.
Similar treatment of a highly metastatic breast cancer model using human serum
albumin-titanocene formulation significantly inhibited cancer growth. This
strategy expands the use of phototherapy for treating previously inaccessible
metastatic disease.
PMID- 29348539
TI - Characterization of a Novel Tectivirus Phage Toil and Its Potential as an Agent
for Biolipid Extraction.
AB - : The oleaginous bacterium Rhodococcus opacus PD630 is metabolically diverse and
can be cultivated on various renewable resources to serve as a sustainable
triacylglycerol (TAG) feedstock for biodiesel production. Current methods for TAG
extraction are costly, but infection of cultures by lytic bacteriophages (phages)
may be a viable approach for achieving release of intracellular lipid from
oleaginous bacteria such as R. opacus. This study reports the novel tectiviral
phage Toil capable of releasing intracellular contents including a fluorescent
protein marker and TAGs into the supernatant after phage infection of R. opacus
PD631, a domesticated derivative of strain PD630. Phage Toil is placed in the
Tectiviridae by its morphology, the presence of a lipid membrane, its genome
architecture and the presence of terminal covalently-linked proteins. Toil is the
first tectivirus capable of infecting a member of the Actinobacteria. Microscopy
shows that infected cells do not undergo sudden lysis but instead maintain their
original shape for several hours, with the cellular morphology gradually
deteriorating. Approximately 30% of intracellular TAGs could be recovered from
the culture supernatants of Toil-infected PD631 cells. Phage Toil has potential
to be used as an agent in extraction of TAGs from oleaginous bacterium R. opacus.
IMPORTANCE: This study reported the first tectivirus (Phage Toil) capable of
infecting a member of the Actinobacteria. In this study, we showed that Phage
Toil can infect oleaginous bacterium Rhodococcus opacus to release intracellular
contents such as a fluorescent protein marker and TAG lipid granules, which can
serve as a starting material for biodiesel production. This study demonstrates a
new method to extract TAGs by using this phage. Additionally, Phage Toil can be a
new model phage to advance knowledge regarding phage infection mechanisms in
Rhodococcus and other mycolic acid-containing bacteria such as Mycobacterium.
PMID- 29348541
TI - Neurodegenerative disease: TDP pathology leads to nuclear disruption.
PMID- 29348540
TI - Human colorectal cancer-derived mesenchymal stem cells promote colorectal cancer
progression through IL-6/JAK2/STAT3 signaling.
AB - Mesenchymal stem cells (MSCs) have been reported to localize in colorectal
carcinomas, and participate in the formation of the tumor microenvironment. They
have recently been isolated from colorectal cancer tissues, and are implicated in
the growth, invasion, and metastasis of cancer cells. However, the roles and
detailed mechanisms associated with human colorectal cancer-derived MSCs (CC
MSCs) have not been fully addressed. In this study, we found that CC-MSCs
increased the migration and invasion of colorectal cancer cells and promoted the
tumorigenesis of colorectal cancer through epithelial-to-mesenchymal transition
(EMT) in vitro. We also found that CC-MSCs enhanced the growth and metastasis of
colorectal cancer in vivo. Mechanistically, we determined that interleukin-6 (IL
6) was the most highly expressed cytokine in the CC-MSC conditioned medium, and
promoted the progression of colorectal cancer cells through IL-6/JAK2/STAT3
signaling, which activated PI3K/AKT signaling. We used anti-IL-6 antibody to
target IL-6. Collectively, these results reveal that the IL-6 secreted by CC-MSCs
enhances the progression of colorectal cancer cells through IL-6/JAK2/STAT3
signaling, and could provide a novel therapeutic or preventive target.
PMID- 29348542
TI - Sensory systems: Bimodal cochlear nucleus stimulation alleviates tinnitus.
PMID- 29348543
TI - Stroke in 2017: Intensive and extensive - advances in stroke management.
PMID- 29348544
TI - Motor neuron disease: A prospective natural history study of type 1 spinal
muscular atrophy.
PMID- 29348545
TI - Motor neuron disease in 2017: Progress towards therapy in motor neuron disease.
PMID- 29348546
TI - Epilepsy in 2017: Precision medicine drives epilepsy classification and therapy.
PMID- 29348547
TI - High strength nanostructured Al-based alloys through optimized processing of
rapidly quenched amorphous precursors.
AB - We report the methods increasing both strength and ductility of aluminum alloys
transformed from amorphous precursor. The mechanical properties of bulk samples
produced by spark-plasma sintering (SPS) of amorphous Al-Ni-Co-Dy powders at
temperatures above 673 K are significantly enhanced by in-situ crystallization of
nano-scale intermetallic compounds during the SPS process. The spark plasma
sintered Al84Ni7Co3Dy6 bulk specimens exhibit 1433 MPa compressive yield strength
and 1773 MPa maximum strength together with 5.6% plastic strain, respectively.
The addition of Dy enhances the thermal stability of primary fcc Al in the
amorphous Al-TM -RE alloy. The precipitation of intermetallic phases by
crystallization of the remaining amorphous matrix plays important role to
restrict the growth of the fcc Al phase and contributes to the improvement of the
mechanical properties. Such fully crystalline nano- or ultrafine-scale Al-Ni-Co
Dy systems are considered promising for industrial application because their
superior mechanical properties in terms of a combination of very high room
temperature strength combined with good ductility.
PMID- 29348548
TI - The global epidemiology of bladder cancer: a joinpoint regression analysis of its
incidence and mortality trends and projection.
AB - We tested the hypotheses that the global incidence of bladder cancer was
increasing but its mortality was reducing and its incidence was positively
correlated with country-specific socioeconomic development. We retrieved data on
age-standardized incidence and mortality rates/100,000 from the GLOBOCAN database
in 2012. Temporal patterns were examined for 39 countries from the Cancer
Incidence in Five Continents volumes I-X and other national registries. We
evaluated the correlation between the incidence/mortality rates and Human
Development Index (HDI)/ logarithmic values of Gross Domestic Product per capita
(GDP). The average annual percent change of the incidence and mortality rates in
the most recent 10 years was examined by joinpoint regression analysis. The
highest incidence rates were observed in Southern Europe, Western Europe and
North America. The mortality rates were the highest in Western Asia and Northern
Africa. The incidence was positively correlated with HDI (r = 0.66 [men]; r =
0.50 [women]) and to a lesser extent logarithmic values of GDP per capita (r =
0.60 [men]; r = 0.50 [women], all p < 0.01). Many European countries experienced
incidence rise. A substantial mortality reduction was observed in most countries,
yet increases in mortality rates were observed in the Philippines and Iceland.
These findings identified countries where more preventive actions are required.
PMID- 29348549
TI - Preoperative anemia in colorectal cancer: relationships with tumor
characteristics, systemic inflammation, and survival.
AB - Anemia is common in colorectal cancer (CRC) but its relationships with tumor
characteristics, systemic inflammation, and survival have not been well
characterized. In this study, blood hemoglobin levels and erythrocyte mean
corpuscular volume (MCV) levels were measured in two independent cohorts of 148
CRC patients and 208 CRC patients, and their correlation with patient and tumor
characteristics, systemic inflammatory markers (modified Glasgow Prognostic
Score: mGPS; serum levels of thirteen cytokines, C-reactive protein, albumin),
and survival were analyzed. We found that anemia, most frequently normocytic,
followed by microcytic, was present in 43% of the patients. Microcytic anemia was
most commonly associated with proximal colon tumor location. Average MCV and
blood hemoglobin levels were lower in tumors with high T-class. Low blood
hemoglobin associated with systemic inflammation, including high mGPS and high
serum levels of C-reactive protein and IL-8. Particularly, normocytic anemia
associated with higher mGPS. Normocytic anemia associated with a tendency towards
worse overall survival (multivariate hazard ratio 1.61, 95% confidence interval
1.07-2.42, p = 0.023; borderline statistical significance considering multiple
hypothesis testing). In conclusion, anemia in CRC patients is most frequently
normocytic. Proximal tumor location is associated with predominantly microcytic
anemia and systemic inflammation is associated with normocytic anemia.
PMID- 29348550
TI - Bimolecular recombination in methylammonium lead triiodide perovskite is an
inverse absorption process.
AB - Photovoltaic devices based on metal halide perovskites are rapidly improving in
efficiency. Once the Shockley-Queisser limit is reached, charge-carrier
extraction will be limited only by radiative bimolecular recombination of
electrons with holes. Yet, this fundamental process, and its link with material
stoichiometry, is still poorly understood. Here we show that bimolecular charge
carrier recombination in methylammonium lead triiodide perovskite can be fully
explained as the inverse process of absorption. By correctly accounting for
contributions to the absorption from excitons and electron-hole continuum states,
we are able to utilise the van Roosbroeck-Shockley relation to determine
bimolecular recombination rate constants from absorption spectra. We show that
the sharpening of photon, electron and hole distribution functions significantly
enhances bimolecular charge recombination as the temperature is lowered,
mirroring trends in transient spectroscopy. Our findings provide vital
understanding of band-to-band recombination processes in this hybrid perovskite,
which comprise direct, fully radiative transitions between thermalized electrons
and holes.
PMID- 29348551
TI - Designable and dynamic single-walled stiff nanotubes assembled from sequence
defined peptoids.
AB - Despite recent advances in the assembly of organic nanotubes, conferral of
sequence-defined engineering and dynamic response characteristics to the tubules
remains a challenge. Here we report a new family of highly designable and dynamic
nanotubes assembled from sequence-defined peptoids through a unique "rolling-up
and closure of nanosheet" mechanism. During the assembly process, amorphous
spherical particles of amphiphilic peptoid oligomers crystallize to form well
defined nanosheets before folding to form single-walled nanotubes. These
nanotubes undergo a pH-triggered, reversible contraction-expansion motion. By
varying the number of hydrophobic residues of peptoids, we demonstrate tuning of
nanotube wall thickness, diameter, and mechanical properties. Atomic force
microscopy-based mechanical measurements show peptoid nanotubes are highly stiff
(Young's Modulus ~13-17 GPa). We further demonstrate the precise incorporation of
functional groups within nanotubes and their applications in water
decontamination and cellular adhesion and uptake. These nanotubes provide a
robust platform for developing biomimetic materials tailored to specific
applications.
PMID- 29348552
TI - TPGLDA: Novel prediction of associations between lncRNAs and diseases via lncRNA
disease-gene tripartite graph.
AB - Accumulating evidences have indicated that lncRNAs play an important role in
various human complex diseases. However, known disease-related lncRNAs are still
comparatively small in number, and experimental identification is time-consuming
and labor-intensive. Therefore, developing a useful computational method for
inferring potential associations between lncRNAs and diseases has become a hot
topic, which can significantly help people to explore complex human diseases at
the molecular level and effectively advance the quality of disease diagnostics,
therapy, prognosis and prevention. In this paper, we propose a novel prediction
of lncRNA-disease associations via lncRNA-disease-gene tripartite graph (TPGLDA),
which integrates gene-disease associations with lncRNA-disease associations.
Compared to previous studies, TPGLDA can be used to better delineate the
heterogeneity of coding-non-coding genes-disease association and can effectively
identify potential lncRNA-disease associations. After implementing the leave-one
out cross validation, TPGLDA achieves an AUC value of 93.9% which demonstrates
its good predictive performance. Moreover, the top 5 predicted rankings of lung
cancer, hepatocellular carcinoma and ovarian cancer are manually confirmed by
different relevant databases and literatures, affording convincing evidence of
the good performance as well as potential value of TPGLDA in identifying
potential lncRNA-disease associations. Matlab and R codes of TPGLDA can be found
at following: https://github.com/USTC-HIlab/TPGLDA .
PMID- 29348553
TI - Night eating model shows time-specific depression-like behavior in the forced
swimming test.
AB - The circadian clock system is associated with feeding and mood. Patients with
night eating syndrome (NES) delay their eating rhythm and their mood declines
during the evening and night, manifesting as time-specific depression. Therefore,
we hypothesized that the NES feeding pattern might cause time-specific
depression. We established new NES model by restricted feeding with high-fat diet
during the inactive period under normal-fat diet ad libitum. The FST (forced
swimming test) immobility time in the NES model group was prolonged only after
lights-on, corresponding to evening and early night for humans. We examined the
effect of the NES feeding pattern on peripheral clocks using PER2::LUCIFERASE
knock-in mice and an in vivo monitoring system. Caloric intake during the
inactive period would shift the peripheral clock, and might be an important
factor in causing the time-specific depression-like behavior. In the NES model
group, synthesis of serotonin and norepinephrine were increased, but utilization
and metabolism of these monoamines were decreased under stress. Desipramine
shortened some mice's FST immobility time in the NES model group. The present
study suggests that the NES feeding pattern causes phase shift of peripheral
clocks and malfunction of the monoamine system, which may contribute to the
development of time-specific depression.
PMID- 29348554
TI - Effects of CO2 enrichment on benthic primary production and inorganic nitrogen
fluxes in two coastal sediments.
AB - Ocean acidification may alter the cycling of nitrogen in coastal sediment and so
the sediment-seawater nitrogen flux, an important driver of pelagic productivity.
To investigate how this perturbation affects the fluxes of NOX-
(nitrite/nitrate), NH4+ and O2, we incubated estuarine sand and subtidal silt in
recirculating seawater with a CO2-adjusted pH of 8.1 and 7.9. During a 41-day
incubation, the seawater kept at pH 8.1 lost 97% of its NOX- content but the
seawater kept at pH 7.9 lost only 18%. Excess CO2 increased benthic
photosynthesis. In the silt, this was accompanied by a reversal of the initial
NOX- efflux into influx. The estuarine sand sustained its initial NOX- influx
but, by the end of the incubation, released more NH4+ at pH 7.9 than at pH 8.1.
We hypothesise that these effects share a common cause; excess CO2 increased the
growth of benthic microalgae and so nutrient competition with ammonia oxidising
bacteria (AOB). In the silt, diatoms likely outcompeted AOB for NH4+ and
photosynthesis increased the dark/light fluctuations in the pore water
oxygenation inhibiting nitrification and coupled nitrification/denitrification.
If this is correct, then excess CO2 may lead to retention of inorganic nitrogen
adding to the pressures of increasing coastal eutrophication.
PMID- 29348556
TI - Puromycin labeling does not allow protein synthesis to be measured in energy
starved cells.
PMID- 29348555
TI - Novel Immunoinformatics Approaches to Design Multi-epitope Subunit Vaccine for
Malaria by Investigating Anopheles Salivary Protein.
AB - Malaria fever has been pervasive for quite a while in tropical developing regions
causing high morbidity and mortality. The causal organism is a protozoan parasite
of genus Plasmodium which spreads to the human host by the bite of hitherto
infected female Anopheles mosquito. In the course of biting, a salivary protein
of Anopheles helps in blood feeding behavior and having the ability to elicit the
host immune response. This study represents a series of immunoinformatics
approaches to design multi-epitope subunit vaccine using Anopheles mosquito
salivary proteins. Designed subunit vaccine was evaluated for its immunogenicity,
allergenicity and physiochemical parameters. To enhance the stability of vaccine
protein, disulfide engineering was performed in a region of high mobility. Codon
adaptation and in silico cloning was also performed to ensure the higher
expression of designed subunit vaccine in E. coli K12 expression system. Finally,
molecular docking and simulation study was performed for the vaccine protein and
TLR-4 receptor, to determine the binding free energy and complex stability.
Moreover, the designed subunit vaccine was found to induce anti-salivary immunity
which may have the ability to prevent the entry of Plasmodium sporozoites into
the human host.
PMID- 29348557
TI - Sensitizing tumor cells to conventional drugs: HSP70 chaperone inhibitors, their
selection and application in cancer models.
AB - Hsp70 chaperone controls proteostasis and anti-stress responses in rapidly
renewing cancer cells, making it an important target for therapeutic compounds.
To date several Hsp70 inhibitors are presented with remarkable anticancer
activity, however their clinical application is limited by the high toxicity
towards normal cells. This study aimed to develop assays to search for the
substances that reduce the chaperone activity of Hsp70 and diminish its
protective function in cancer cells. On our mind the resulting compounds alone
should be safe and function in combination with drugs widely employed in
oncology. We constructed systems for the analysis of substrate-binding and
refolding activity of Hsp70 and to validate the assays screened the substances
representing most diverse groups of chemicals of InterBioScreen library. One of
the inhibitors was AEAC, an N-amino-ethylamino derivative of colchicine, which
toxicity was two-orders lower than that of parent compound. In contrast to
colchicine, AEAC inhibited substrate-binding and refolding functions of Hsp70
chaperones. The results of a drug affinity responsive target stability assay,
microscale thermophoresis and molecular docking show that AEAC binds Hsp70 with
nanomolar affinity. AEAC was found to penetrate C6 rat glioblastoma and B16 mouse
melanoma cells and reduce there the function of the Hsp70-mediated refolding
system. Although the cytotoxic and growth inhibitory activities of AEAC were
minimal, the compound was shown to increase the antitumor efficiency of
doxorubicin in tumor cells of both types. When the tumors were grown in animals,
AEAC administration in combination with doxorubicin exerted maximal therapeutic
effect prolonging animal survival by 10-15 days and reducing tumor growth rate by
60%. To our knowledge, this is the first time that this approach to the high
throughput analysis of chaperone inhibitors has been applied, and it can be
useful in the search for drug combinations that are effective in the treatment of
highly resistant tumors.
PMID- 29348558
TI - Preparation of polyaniline/PbS core-shell nano/microcomposite and its application
for photocatalytic H2 electrogeneration from H2O.
AB - Lead sulfide (PbS) and polyaniline (PANI) nano/microparticles were prepared.
Then, PANI/PbS core-shell nano/microcomposites (I, II, and III) were prepared by
oxidative polymerization of different aniline concentrations (0.01, 0.03, and
0.05 M), respectively, in the presence of 0.05 M PbS. FT-IR, XRD, SEM, HR-TEM,
and UV-Vis analyses were carried out to characterize the samples. From the FT-IR
data, there are redshifts in PbS and PANI nano/microparticles bands in comparison
with PANI/PbS nano/microcomposites. The average crystallite sizes of PANI/PbS
core-shell nano/microcomposites (I, II, and III) from XRD analyses were 46.5, 55,
and 42.16 nm, respectively. From the optical analyses, nano/microcomposite (II)
has the optimum optical properties with two band gaps values of 1.41 and 2.79 eV.
Then, the nano/microcomposite (II) membrane electrode supported on ITO glass was
prepared and applied on the photoelectrochemical (PEC) H2 generation from H2O.
The characteristics current-voltage and current-time behaviors were measured at
different wavelengths from 390 to 636 nm. Also, the incident photon-to-current
conversion efficiency (IPCE) under monochromatic illumination condition was
calculated. The optimum values for IPCE were 36.5 and 35.2% at 390 and 405 nm,
respectively. Finally, a simple mechanism for PEC H2 generation from H2O using
the nano/microcomposite (II) membrane electrode was mentioned.
PMID- 29348559
TI - PLK1 protects against sepsis-induced intestinal barrier dysfunction.
AB - Sepsis and sepsis-associated intestinal barrier dysfunction are common in
intensive care units, with high mortality. The aim of this study is to
investigate whether Polo-like kinase 1 (PLK1) ameliorates sepsis-induced
intestinal barrier dysfunction in the intestinal epithelium. The mouse intestinal
barrier was disrupted after Lipopolysaccharide (LPS) injection due to intestinal
epithelial cell apoptosis and proliferation inhibition, accompanied by decreased
PLK1. In HT-29 intestinal epithelial cells, LPS stimulation induced cell
apoptosis and inhibited cell proliferation. Overexpression of PLK1 partly rescued
the apoptosis and proliferation inhibition in HT29 cells caused by LPS. Finally,
LPS stimulation promoted the reduction of PLK1, resulting in apoptosis and
proliferation inhibition in intestinal epithelial cells, disrupting the
intestinal epithelial barrier. These findings indicate that PLK1 might be a
potential therapeutic target for the treatment of sepsis-induced intestinal
barrier dysfunction.
PMID- 29348560
TI - Discovery of a small-molecule protein kinase Cdelta-selective activator with
promising application in colon cancer therapy.
AB - Protein kinase C (PKC) isozymes play major roles in human diseases, including
cancer. Yet, the poor understanding of isozymes-specific functions and the
limited availability of selective pharmacological modulators of PKC isozymes have
limited the clinical translation of PKC-targeting agents. Here, we report the
first small-molecule PKCdelta-selective activator, the 7alpha-acetoxy-6beta
benzoyloxy-12-O-benzoylroyleanone (Roy-Bz), which binds to the PKCdelta-C1
domain. Roy-Bz potently inhibited the proliferation of colon cancer cells by
inducing a PKCdelta-dependent mitochondrial apoptotic pathway involving caspase-3
activation. In HCT116 colon cancer cells, Roy-Bz specifically triggered the
translocation of PKCdelta but not other phorbol ester responsive PKCs. Roy-Bz
caused a marked inhibition in migration of HCT116 cells in a PKCdelta-dependent
manner. Additionally, the impairment of colonosphere growth and formation,
associated with depletion of stemness markers, indicate that Roy-Bz also targets
drug-resistant cancer stem cells, preventing tumor dissemination and recurrence.
Notably, in xenograft mouse models, Roy-Bz showed a PKCdelta-dependent antitumor
effect, through anti-proliferative, pro-apoptotic, and anti-angiogenic
activities. Besides, Roy-Bz was non-genotoxic, and in vivo it had no apparent
toxic side effects. Collectively, our findings reveal a novel promising
anticancer drug candidate. Most importantly, Roy-Bz opens the way to a new era on
PKC biology and pharmacology, contributing to the potential redefinition of the
structural requirements of isozyme-selective agents, and to the re-establishment
of PKC isozymes as feasible therapeutic targets in human diseases.
PMID- 29348561
TI - Performance analysis of an adaptive optics system for free-space optics
communication through atmospheric turbulence.
AB - The performance of free-space optics communication (FSOC) is greatly degraded by
atmospheric turbulence. Adaptive optics (AO) is an effective method for
attenuating the influence. In this paper, the influence of the spatial and
temporal characteristics of turbulence on the performance of AO in a FSOC system
is investigated. Based on the Greenwood frequency (GF) and the ratio of receiver
aperture diameter to atmospheric coherent length (D/r 0 ), the relationship
between FSOC performance (CE) and AO parameters (corrected Zernike modes number
and bandwidth) is derived for the first time. Then, simulations and experiments
are conducted to analyze the influence of AO parameters on FSOC performance under
different GF and D/r 0 . The simulation and experimental results show that, for
common turbulence conditions, the number of corrected Zernike modes can be fixed
at 35 and the bandwidth of the AO system should be larger than the GF.
Measurements of the bit error rate (BER) for moderate turbulence conditions (D/r
0 = 10, f G = 60 Hz) show that when the bandwidth is two times that of GF, the
average BER is decreased by two orders of magnitude compared with f G /f 3dB =
1. These results and conclusions can provide important guidance in the design of
an AO system for FSOC.
PMID- 29348562
TI - Non-marine palaeoenvironment associated to the earliest tetrapod tracks.
AB - Opinions differ on whether the evolution of tetrapods (limbed vertebrates) from
lobe-finned fishes was directly linked to terrestrialization. The earliest known
tetrapod fossils, from the Middle Devonian (approximately 390 million years old)
of Zachelmie Quarry in Poland, are trackways made by limbs with digits; they
document a direct environmental association and thus have the potential to help
answer this question. However, the tetrapod identity of the tracks has recently
been challenged, despite their well-preserved morphology, on account of their
great age and supposedly shallow marine (intertidal or lagoonal) depositional
environment. Here we present a new palaeoenvironmental interpretation of the
track-bearing interval from Zachelmie, showing that it represents a succession of
ephemeral lakes with a restricted and non-marine biota, rather than a marginal
marine environment as originally thought. This context suggests that the
trackmaker was capable of terrestrial locomotion, consistent with the appendage
morphology recorded by the footprints, and thus provides additional support for a
tetrapod identification.
PMID- 29348563
TI - Disruption of CXCR3 function impedes the development of Sjogren's syndrome-like
xerostomia in non-obese diabetic mice.
AB - The chemokine receptor CXCR3 plays an important role in T cell recruitment in
various immune responses and autoimmune diseases. Expression of CXCR3 ligands,
including CXCL9, CXCL10, and CXCL11, is elevated in the salivary glands of
patients with Sjogren's syndrome (SS). To elucidate whether interaction between
CXCR3 and its ligands is required for the development of SS, we administrated an
anti-CXCR3 blocking antibody (CXCR3-173) to the non-obese diabetic (NOD) mice, a
well-defined model of SS, during the stage prior to disease onset. Treatment with
this anti-CXCR3 antibody significantly improved salivary secretion, indicating a
remission of SS clinical manifestation. Anti-CXCR3 treatment did not affect the
gross leukocyte infiltration of the submandibular glands (SMGs) as assessed by
hematoxylin and eosin staining. However, flow cytometric analysis showed that
anti-CXCR3 treatment markedly reduced the percentage of CXCR3+CD8 T and
CXCR3+CD44+CD8 T cells, without affecting that of CXCR3+CD4 T and CXCR3+CD44+CD4
T cells in the SMGs and submandibular lymph nodes, suggesting a preferential
effect of this anti-CXCR3 treatment on CXCR3-expressing effector CD8 T cells.
Meanwhile, SMG expression of inflammatory factor TNF-alpha was markedly
diminished by anti-CXCR3 treatment. In accordance, anti-CXCR3 significantly
enhanced SMG expression of tight junction protein claudin-1 and water channel
protein aquaporin 5, two molecules that are crucial for normal salivary secretion
and can be down-regulated by TNF-alpha. Taken together, these findings
demonstrated that the interaction between the endogenous CXCR3 and its ligands
plays a pro-inflammatory and pathogenic role in the development of SS-like
xerostomia in the NOD mouse model.
PMID- 29348564
TI - Inhibition of WNT/beta-catenin signaling under serum starvation and hypoxia
induces adipocytic transdifferentiation in human leiomyoma cells.
AB - Fatty metamorphosis is an uncommon alteration in uterine leiomyoma (i.e.,
lipoleiomyoma), and the pathogenetic mechanisms underlying this phenomenon remain
poorly understood. Because a conditional deletion of beta-catenin, a major
transducer of the canonical Wingless/integrated (WNT) pathway, in the developing
mouse uterus can induce adipogenesis in the myometrium, it is hypothesized that
inhibition of the WNT/beta-catenin signaling may be also involved in the
development of fat cells within uterine leiomyoma. In the current study, which
was performed to address this point, intracytoplasmic lipid droplets were
detectable in cultured human leiomyoma cells by treatment with a potent tankyrase
inhibitor, XAV939, which antagonizes beta-catenin, in a serum-starved culture
medium without additional adipogenesis-inducing agents or supplements, and showed
increasing accumulation in a time-dependent manner. In addition, the induction of
fat cells was greatly enhanced under hypoxic conditions (i.e., 2.5% O2)
recapitulating the local in vivo situation of uterine leiomyoma-in comparison to
that under normoxic conditions (i.e., 21% O2). The marker genes of differentiated
fat cells such as ADIPOQ and PLIN were highly expressed in leiomyoma cells that
were treated with XAV939 under hypoxia and serum starvation, whereas the
immunohistochemical expression of desmin-a cytoskeletal protein representing
smooth muscle differentiation-was downregulated, which appears in line with the
switch in differentiation. The results of our study suggest that the inhibition
of canonical WNT/beta-catenin signaling under the stress due to hypoxia and serum
starvation can initiate adipocytic transdifferentiation or metaplasia in human
uterine leiomyoma cells, which is potentially related to the development of
lipoleiomyoma.
PMID- 29348565
TI - An in vitro system of autologous lymphocytes culture that allows the study of
homeostatic proliferation mechanisms in human naive CD4 T-cells.
AB - The size of peripheral T-cell pool is kept constant throughout life. However, a
decline in lymphocyte numbers is a feature of several human disorders, in which
fast and slow homeostatic proliferation play a crucial role. Several in vitro and
in vivo models have been developed to study such processes. Nevertheless, self-
and commensal- antigens, well-known triggers of homeostatic proliferation, have
not been examined in these models. We have designed an in vitro culture of human
T-cells exposed to rIL7 and autologous antigen-presenting cells (aAPC) that
allows the simultaneous characterization of the different types of homeostatic
proliferation. Using our model, we first confirmed that both rIL7 and aAPC are
survival signals ultimately leading to homeostatic proliferation. In addition, we
explored the modulation of different anti-apoptotic, proliferative, activation
and homing markers during fast and slow homeostatic proliferation. Finally,
different subsets of Treg were generated during homeostatic proliferation in our
model. In summary, our in vitro system is able to simultaneously reproduce both
types of homeostatic proliferation of human naive CD4 T-cells, and allows the
characterization of these processes. Our in vitro system is a useful tool to
explore specific features of human homeostatic proliferation in different human
lymphopenia-related disorders and could be used as a cell therapy approach.
PMID- 29348566
TI - Phosphorylation of ULK1 by AMPK is essential for mouse embryonic stem cell self
renewal and pluripotency.
AB - Autophagy is a catabolic process to degrade both damaged organelles and
aggregated proteins in somatic cells. We have recently identified that autophagy
is an executor for mitochondrial homeostasis in embryonic stem cell (ESC), and
thus contribute to stemness regulation. However, the regulatory and functional
mechanisms of autophagy in ESC are still largely unknown. Here we have shown that
activation of ULK1 by AMPK is essential for ESC self-renewal and pluripotency.
Dysfunction of Ulk1 decreases the autophagic flux in ESC, leading to compromised
self-renewal and pluripotency. These defects can be rescued by reacquisition of
wild-type ULK1 and ULK1(S757A) mutant, but not ULK1(S317A, S555A and S777A) and
kinase dead ULK1(K46I) mutant. These data indicate that phosphorylation of ULK1
by AMPK, but not mTOR, is essential for stemness regulation in ESC. The findings
highlight a critical role for AMPK-dependent phosphorylation of ULK1 pathway to
maintain ESC self-renewal and pluripotency.
PMID- 29348567
TI - Optical magnetism in planar metamaterial heterostructures.
AB - Harnessing artificial optical magnetism has previously required complex two- and
three-dimensional structures, such as nanoparticle arrays and split-ring
metamaterials. By contrast, planar structures, and in particular dielectric/metal
multilayer metamaterials, have been generally considered non-magnetic. Although
the hyperbolic and plasmonic properties of these systems have been extensively
investigated, their assumed non-magnetic response limits their performance to
transverse magnetic (TM) polarization. We propose and experimentally validate a
mechanism for artificial magnetism in planar multilayer metamaterials. We also
demonstrate that the magnetic properties of high-index dielectric/metal
hyperbolic metamaterials can be anisotropic, leading to magnetic hyperbolic
dispersion in certain frequency regimes. We show that such systems can support
transverse electric polarized interface-bound waves, analogous to their TM
counterparts, surface plasmon polaritons. Our results open a route for tailoring
optical artificial magnetism in lithography-free layered systems and enable us to
generalize the plasmonic and hyperbolic properties to encompass both linear
polarizations.
PMID- 29348568
TI - Medial preoptic area in mice is capable of mediating sexually dimorphic behaviors
regardless of gender.
AB - The medial preoptic area (mPOA) differs between males and females in nearly all
species examined to date, including humans. Here, using fiber photometry
recordings of Ca2+ transients in freely behaving mice, we show ramping activities
in the mPOA that precede and correlate with sexually dimorphic display of male
typical mounting and female-typical pup retrieval. Strikingly, optogenetic
stimulation of the mPOA elicits similar display of mounting and pup retrieval in
both males and females. Furthermore, by means of recording, ablation, optogenetic
activation, and inhibition, we show mPOA neurons expressing estrogen receptor
alpha (Esr1) are essential for the sexually biased display of these behaviors.
Together, these results underscore the shared layout of the brain that can
mediate sex-specific behaviors in both male and female mice and provide an
important functional frame to decode neural mechanisms governing sexually
dimorphic behaviors in the future.
PMID- 29348569
TI - GenomeLandscaper: Landscape analysis of genome-fingerprints maps assessing
chromosome architecture.
AB - Assessing correctness of an assembled chromosome architecture is a central
challenge. We create a geometric analysis method (called GenomeLandscaper) to
conduct landscape analysis of genome-fingerprints maps (GFM), trace large-scale
repetitive regions, and assess their impacts on the global architectures of
assembled chromosomes. We develop an alignment-free method for phylogenetics
analysis. The human Y chromosomes (GRCh.chrY, HuRef.chrY and YH.chrY) are
analysed as a proof-of-concept study. We construct a galaxy of genome
fingerprints maps (GGFM) for them, and a landscape compatibility among relatives
is observed. But a long sharp straight line on the GGFM breaks such a landscape
compatibility, distinguishing GRCh38p1.chrY (and throughout GRCh38p7.chrY) from
GRCh37p13.chrY, HuRef.chrY and YH.chrY. We delete a 1.30-Mbp target segment to
rescue the landscape compatibility, matching the antecedent GRCh37p13.chrY. We re
locate it into the modelled centromeric and pericentromeric region of
GRCh38p10.chrY, matching a gap placeholder of GRCh37p13.chrY. We decompose it
into sub-constituents (such as BACs, interspersed repeats, and tandem repeats)
and trace their homologues by phylogenetics analysis. We elucidate that most
examined tandem repeats are of reasonable quality, but the BAC-sized repeats,
173U1020C (176.46 Kbp) and 5U41068C (205.34 Kbp), are likely over-repeated. These
results offer unique insights into the centromeric and pericentromeric regions of
the human Y chromosomes.
PMID- 29348570
TI - Systematic in vivo evaluation of the time-dependent inflammatory response to
steel and Teflon insulin infusion catheters.
AB - Continuous subcutaneous insulin infusion (CSII) catheters are considered the weak
link of insulin pump therapy. Wear-time considerably varies between patients and
the choice of catheter material is based on personal preferences rather than
scientific facts. Therefore, we systematically assessed and quantified the
inflammatory tissue response to steel versus Teflon CSII catheters over a maximum
wear-time of 7 days in swine. Tissue surrounding catheters was analysed using
histopathology and quantitative real-time PCR. The area of inflammation increased
significantly over time independent of material which was confirmed by an
increase in CD68 expression and an increase in mononuclear and neutrophil cell
infiltrate around the catheters. We observed substantially higher fibrin
deposition (p < 0.05) around steel on day 4 of wear-time. IL-6 gene expression
increased within 24 hours after insertion, returned to normal levels around
Teflon (p < 0.05) but remained high around steel (p < 0.05). IL-10 and TGF-beta
levels did not resolve over time, indicating impaired wound healing. In
conclusion, there was a major temporal effect in the acute inflammatory response
to CSII catheters but we found little difference between materials. This study
setup presents a robust tool for the systematic analysis of the tissue response
to CSII catheters.
PMID- 29348571
TI - High resolution time series reveals cohesive but short-lived communities in
coastal plankton.
AB - Because microbial plankton in the ocean comprise diverse bacteria, algae, and
protists that are subject to environmental forcing on multiple spatial and
temporal scales, a fundamental open question is to what extent these organisms
form ecologically cohesive communities. Here we show that although all taxa
undergo large, near daily fluctuations in abundance, microbial plankton are
organized into clearly defined communities whose turnover is rapid and sharp. We
analyze a time series of 93 consecutive days of coastal plankton using a
technique that allows inference of communities as modular units of interacting
taxa by determining positive and negative correlations at different temporal
frequencies. This approach shows both coordinated population expansions that
demarcate community boundaries and high frequency of positive and negative
associations among populations within communities. Our analysis thus highlights
that the environmental variability of the coastal ocean is mirrored in sharp
transitions of defined but ephemeral communities of organisms.
PMID- 29348572
TI - Areca nut extracts mobilize calcium and release pro-inflammatory cytokines from
various immune cells.
AB - Betel nut consumption has significant implications for the public health
globally, as the wide-spread habit of Areca chewing throughout Asia and the
Pacific is associated with a high prevalence of oral carcinoma and other
diseases. Despite a clear causal association of betel nut chewing and oral
mucosal diseases, the biological mechanisms that link Areca nut-contained
molecules, inflammation and cancer remain underexplored. In this study we show
that the whole Areca nut extract (ANE) is capable of mobilizing Ca2+ in various
immune cell lines. Interestingly, none of the four major alkaloids or a range of
other known constituents of Areca nut were able to induce such Ca2+ signals,
suggesting that the active components might represent novel or so far
unappreciated chemical structures. The separation of ANE into aqueous and organic
fractions has further revealed that the calcium-mobilizing molecules are
exclusively present in the aqueous extract. In addition, we found that these
calcium signals are associated with the activation of several immune cell lines
as shown by the release of pro-inflammatory cytokines and increased cell
proliferation. These results indicate that calcium-mobilizing molecules present
in the aqueous fraction of the Areca nut may critically contribute to the
inflammatory disorders affecting betel nut chewers.
PMID- 29348574
TI - Full-body physical therapy evaluation for pre- and post-hematopoietic cell
transplant patients and the need for a modified rehabilitation musculoskeletal
specific grading system for chronic graft-versus-host disease.
PMID- 29348573
TI - Exendin-4-encapsulated dissolving microneedle arrays for efficient treatment of
type 2 diabetes.
AB - Dissolving microneedles (DMNs) are microscopic needles capable of delivering
encapsulated compounds and releasing them into the skin in a minimally invasive
manner. Most studies indicate that encapsulating therapeutics in DMNs is an
efficacious approach; however, the importance of evaluating the activity of
encapsulated compounds, during the fabrication process, has not been examined in
detail. Conducting an analysis of thermal, chemical, and physical stress factors,
including temperature, pH, and the interaction of the polymer and therapeutics
mixture during preparation, is essential for retaining the activity of
encapsulated therapeutics during and after fabrication. Here, we optimised the
thermal, chemical, and physical parameters for the fabrication of exendin-4 (Ex
4)-encapsulated DMNs (Ex-4 DMNs). Ex-4, a peptide agonist of glucagon-like
peptide (GLP) receptor, is used for glycaemic control in patients with type 2
diabetes. Our findings indicate that optimising the parameters involved in DMN
fabrication retained the activity of Ex-4 by up to 98.3 +/- 1.5%. Ex-4 DMNs
reduced the blood-glucose level in diabetic mice with efficiency similar to that
of a subcutaneous injection. We believe that this study paves way for the
commercialisation of an efficient and minimally invasive treatment for patients
with type 2 diabetes.
PMID- 29348575
TI - Quantitative optical nanophysiology of Ca2+ signaling at inner hair cell active
zones.
AB - Ca2+ influx triggers the release of synaptic vesicles at the presynaptic active
zone (AZ). A quantitative characterization of presynaptic Ca2+ signaling is
critical for understanding synaptic transmission. However, this has remained
challenging to establish at the required resolution. Here, we employ confocal and
stimulated emission depletion (STED) microscopy to quantify the number (20-330)
and arrangement (mostly linear 70 nm * 100-600 nm clusters) of Ca2+ channels at
AZs of mouse cochlear inner hair cells (IHCs). Establishing STED Ca2+ imaging, we
analyze presynaptic Ca2+ signals at the nanometer scale and find confined
elongated Ca2+ domains at normal IHC AZs, whereas Ca2+ domains are spatially
spread out at the AZs of bassoon-deficient IHCs. Performing 2D-STED fluorescence
lifetime analysis, we arrive at estimates of the Ca2+ concentrations at
stimulated IHC AZs of on average 25 uM. We propose that IHCs form bassoon
dependent presynaptic Ca2+-channel clusters of similar density but scalable
length, thereby varying the number of Ca2+ channels amongst individual AZs.
PMID- 29348576
TI - Redundancy of protein disulfide isomerases in the catalysis of the inactivating
disulfide switch in A Disintegrin and Metalloprotease 17.
AB - A Disintegrin and Metalloprotease 17 (ADAM17) can cause the fast release of
growth factors and inflammatory mediators from the cell surface. Its activity has
to be turned on which occurs by various stimuli. The active form can be
inactivated by a structural change in its ectodomain, related to the pattern of
the formed disulphide bridges. The switch-off is executed by protein disulfide
isomerases (PDIs) that catalyze an isomerization of two disulfide bridges and
thereby cause a disulfide switch. We demonstrate that the integrity of the CGHC
motif within the active site of PDIs is indispensable. In particular, no major
variation is apparent in the activities of the two catalytic domains of PDIA6.
The affinities between PDIA1, PDIA3, PDIA6 and the targeted domain of ADAM17 are
all in the nanomolar range and display no significant differences. The redundancy
between PDIs and their disulfide switch activity in ectodomains of transmembrane
proteins found in vitro appears to be a basic characteristic. However, different
PDIs might be required in vivo for disulfide switches in different tissues and
under different cellular and physiological situations.
PMID- 29348577
TI - Targeting B cell receptor signalling in cancer: preclinical and clinical
advances.
AB - B cell receptor (BCR) signalling is crucial for normal B cell development and
adaptive immunity. BCR signalling also supports the survival and growth of
malignant B cells in patients with B cell leukaemias or lymphomas. The mechanism
of BCR pathway activation in these diseases includes continuous BCR stimulation
by microbial antigens or autoantigens present in the tissue microenvironment,
activating mutations within the BCR complex or downstream signalling components
and ligand-independent tonic BCR signalling. The most established agents
targeting BCR signalling are Bruton tyrosine kinase (BTK) inhibitors and PI3K
isoform-specific inhibitors, and their introduction into the clinic is rapidly
changing how B cell malignancies are treated. B cells and BCR-related kinases,
such as BTK, also play a role in the microenvironment of solid tumours, such as
squamous cell carcinoma and pancreatic cancer, and therefore targeting B cells or
BCR-related kinases may have anticancer activity beyond B cell malignancies.
PMID- 29348579
TI - Structural basis of SALM5-induced PTPdelta dimerization for synaptic
differentiation.
AB - SALM5, a synaptic adhesion molecule implicated in autism, induces presynaptic
differentiation through binding to the LAR family receptor protein tyrosine
phosphatases (LAR-RPTPs) that have been highlighted as presynaptic hubs for
synapse formation. The mechanisms underlying SALM5/LAR-RPTP interaction remain
unsolved. Here we report crystal structures of human SALM5 LRR-Ig alone and in
complex with human PTPdelta Ig1-3 (MeA-). Distinct from other LAR-RPTP ligands,
SALM5 mainly exists as a dimer with LRR domains from two protomers packed in an
antiparallel fashion. In the 2:2 heterotetrameric SALM5/PTPdelta complex, a SALM5
dimer bridges two separate PTPdelta molecules. Structure-guided mutations and
heterologous synapse formation assays demonstrate that dimerization of SALM5 is
prerequisite for its functionality in inducing synaptic differentiation. This
study presents a structural template for the SALM family and reveals a mechanism
for how a synaptic adhesion molecule directly induces cis-dimerization of LAR
RPTPs into higher-order signaling assembly.
PMID- 29348580
TI - The epibiotic life of the cosmopolitan diatom Fragilariopsis doliolus on
heterotrophic ciliates in the open ocean.
AB - Diatoms are a diverse and ecologically important group of phytoplankton. Although
most species are considered free living, several are known to interact with other
organisms within the plankton. Detailed imaging and molecular characterization of
any such partnership is, however, limited, and an appraisal of the large-scale
distribution and ecology of such consortia was never attempted. Here, observation
of Tara Oceans samples from the Benguela Current led to the detection of an
epibiotic association between a pennate diatom and a tintinnid ciliate. We
identified the diatom as Fragilariopsis doliolus that possesses a unique feature
to form barrel-shaped chains, associated with seven different genera of
tintinnids including five previously undescribed associations. The organisms were
commonly found together in the Atlantic and Pacific Ocean basins, and live
observations of the interaction have been recorded for the first time. By
combining confocal and scanning electron microscopy of individual consortia with
the sequencing of high-resolution molecular markers, we analyzed their
distribution in the global ocean, revealing morpho-genetically distinct tintinnid
haplotypes and biogeographically structured diatom haplotypes. The diatom was
among the most abundant in the global ocean. We show that the consortia were
particularly prevalent in nutrient-replete conditions, rich in potential
predators. These observations support the hypothesis of a mutualistic symbiosis,
wherein diatoms acquire increased motility and tintinnids benefit from
silicification through increased protection, and highlight that such associations
may be more prevalent than currently appreciated.
PMID- 29348578
TI - A matter of life and death: stem cell survival in tissue regeneration and tumour
formation.
AB - In recent years, great strides have been made in our understanding of how stem
cells (SCs) govern tissue homeostasis and regeneration. The inherent longevity of
SCs raises the possibility that the unique protective mechanisms in these cells
might also be involved in tumorigenesis. In this Opinion article, we discuss how
SCs are protected throughout their lifespan, focusing on quiescent behaviour, DNA
damage response and programmed cell death. We briefly examine the roles of adult
SCs and progenitors in tissue repair and tumorigenesis and explore how signals
released from dying or dormant cells influence the function of healthy or
aberrant SCs. Important insight into the mechanisms that regulate SC death and
survival, as well as the 'legacy' imparted by departing cells, may unlock novel
avenues for regenerative medicine and cancer therapy.
PMID- 29348581
TI - Identifying metabolic pathways for production of extracellular polymeric
substances by the diatom Fragilariopsis cylindrus inhabiting sea ice.
AB - Diatoms are significant primary producers in sea ice, an ephemeral habitat with
steep vertical gradients of temperature and salinity characterizing the ice
matrix environment. To cope with the variable and challenging conditions, sea ice
diatoms produce polysaccharide-rich extracellular polymeric substances (EPS) that
play important roles in adhesion, cell protection, ligand binding and as organic
carbon sources. Significant differences in EPS concentrations and chemical
composition corresponding to temperature and salinity gradients were present in
sea ice from the Weddell Sea and Eastern Antarctic regions of the Southern Ocean.
To reconstruct the first metabolic pathway for EPS production in diatoms, we
exposed Fragilariopsis cylindrus, a key bi-polar diatom species, to simulated sea
ice formation. Transcriptome profiling under varying conditions of EPS production
identified a significant number of genes and divergent alleles. Their complex
differential expression patterns under simulated sea ice formation was aligned
with physiological and biochemical properties of the cells, and with field
measurements of sea ice EPS characteristics. Thus, the molecular complexity of
the EPS pathway suggests metabolic plasticity in F. cylindrus is required to cope
with the challenging conditions of the highly variable and extreme sea ice
habitat.
PMID- 29348582
TI - Nanostructured titanium surfaces exhibit recalcitrance towards Staphylococcus
epidermidis biofilm formation.
AB - Titanium-based implants are ubiquitous in the healthcare industries and often
suffer from bacterial attachment which results in infections. An innovative
method of reducing bacterial growth is to employ nanostructures on implant
materials that cause contact-dependent cell death by mechanical rupture of
bacterial cell membranes. To achieve this, we synthesized nanostructures with
different architectures on titanium surfaces using hydrothermal treatment
processes and then examined the growth of Staphylococcus epidermidis on these
surfaces. The structure obtained after a two-hour hydrothermal treatment
(referred to as spear-type) showed the least bacterial attachment at short times
but over a period of 6 days tended to support the formation of thick biofilms. By
contrast, the structure obtained after a three-hour hydrothermal treatment
(referred to as pocket-type) was found to delay biofilm formation up to 6 days
and killed 47% of the initially attached bacteria by penetrating or compressing
the bacteria in between the network of intertwined nano-spears. The results point
to the efficacy of pocket-type nanostructure in increasing the killing rate of
individual bacteria and potentially delaying longer-term biofilm formation.
PMID- 29348583
TI - Rapid updating of spatial working memory across saccades.
AB - Each time we make an eye movement, positions of objects on the retina change. In
order to keep track of relevant objects their positions have to be updated. The
situation becomes even more complex if the object is no longer present in the
world and has to be held in memory. In the present study, we used saccadic
curvature to investigate the time-course of updating a memorized location across
saccades. Previous studies have shown that a memorized location competes with a
saccade target for selection on the oculomotor map, which leads to saccades
curving away from it. In our study participants performed a sequence of two
saccades while keeping a location in memory. The trajectory of the second saccade
was used to measure when the memorized location was updated after the first
saccade. The results showed that the memorized location was rapidly updated with
the eyes curving away from its spatial coordinates within 130 ms after the first
eye movement. The time-course of updating was comparable to the updating of an
exogenously attended location, and depended on how well the location was
memorized.
PMID- 29348584
TI - Quail egg homogenate alleviates food allergy induced eosinophilic esophagitis
like disease through modulating PAR-2 transduction pathway in peanut sensitized
mice.
AB - The present pharmacotherapy for eosinophilic esophagitis (EoE) fundamentally
depend on inhaled corticosteroids. Despite the fact that oral intake of topical
steroids can be successful in restricting EoE-related inflammation, there are
concerns with respect to the long term utilization of steroids, especially in
kids. In the current research, we assess the effect of quail egg, which is
reportedly a known serine protease inhibitor, on symptomatology and immune
responses in a peanut-sensitized mouse model of food allergy induced EoE. Daily
oral treatment with quail egg attenuated mice symptomatology and immune response.
Treatment with quail egg inhibited antigen-prompted increments in mouse tryptase
and eosinophil cationic protein (ECP) in serum and eosinophil in inflamed tissues
like oesophagus, lung, and digestive system. Quail egg treatment resulted in
decreased antibody specific IgE and IgG1 and a variety of inflammatory genes that
were abnormally expressed in EoE. Other effects included increased IL-10,
decreased PAR-2 activation and NF-kB p65 in inflamed tissues. Our results suggest
that quail egg treatment may have therapeutic potential in attenuating the
symptoms of food allergy induced EoE like disease through regulating PAR-2
downstream pathway by blocking the activation of the transcription factor NF-kB
p65 activity.
PMID- 29348585
TI - A surrogate reporter system for multiplexable evaluation of CRISPR/Cas9 in
targeted mutagenesis.
AB - Engineered nucleases in genome editing manifest diverse efficiencies at different
targeted loci. There is therefore a constant need to evaluate the mutation rates
at given loci. T7 endonuclease 1 (T7E1) and Surveyor mismatch cleavage assays are
the most widely used methods, but they are labour and time consuming, especially
when one must address multiple samples in parallel. Here, we report a surrogate
system, called UDAR (Universal Donor As Reporter), to evaluate the efficiency of
CRISPR/Cas9 in targeted mutagenesis. Based on the non-homologous end-joining
(NHEJ)-mediated knock-in strategy, the UDAR-based assay allows us to rapidly
evaluate the targeting efficiencies of sgRNAs. With one-step transfection and
fluorescence-activated cell sorting (FACS) analysis, the UDAR assay can be
completed on a large scale within three days. For detecting mutations generated
by the CRISPR/Cas9 system, a significant positive correlation was observed
between the results from the UDAR and T7E1 assays. Consistently, the UDAR assay
could quantitatively assess bleomycin- or ICRF193-induced double-strand breaks
(DSBs), which suggests that this novel strategy is broadly applicable to
assessing the DSB-inducing capability of various agents. With the increasing
impact of genome editing in biomedical studies, the UDAR method can significantly
benefit the evaluation of targeted mutagenesis, especially for high-throughput
purposes.
PMID- 29348586
TI - Analogues of Disulfides from Allium stipitatum Demonstrate Potent Anti-tubercular
Activities through Drug Efflux Pump and Biofilm Inhibition.
AB - Disulfides from Allium stipitatum, commonly known as Persian shallot, were
previously reported to possess antibacterial properties. Analogues of these
compounds, produced by S-methylthiolation of appropriate thiols using S-methyl
methanethiosulfonate, exhibited antimicrobial activity, with one compound
inhibiting the growth of Mycobacterium tuberculosis at 17 uM (4 mg L-1) and other
compounds inhibiting Escherichia coli and multi-drug-resistant (MDR)
Staphylococcus aureus at concentrations ranging between 32-138 uM (8-32 mg L-1).
These compounds also displayed moderate inhibitory effects on Klebsiella and
Proteus species. Whole-cell phenotypic bioassays such as the spot-culture growth
inhibition assay (SPOTi), drug efflux inhibition, biofilm inhibition and
cytotoxicity assays were used to evaluate these compounds. Of particular note was
their ability to inhibit mycobacterial drug efflux and biofilm formation, while
maintaining a high selectivity towards M. tuberculosis H37Rv. These results
suggest that methyl disulfides are novel scaffolds which could lead to the
development of new drugs against tuberculosis (TB).
PMID- 29348588
TI - Two-color second-order sideband generation in an optomechanical system with a two
level system.
AB - Second-order sideband generation in an optomechanical system with the coupling
between a mechanical resonator and a two-level system is discussed beyond the
conventional linearized description of optomechanical interactions. The features
of two-color second-order sideband generation are demonstrated in this hybrid
system. We discovery that the switch between one- and two-color second-order
sideband generation is easily realized by shifting the detuning between the
control field and the cavity field or the transition frequency of the two-level
system. The efficiency of two-color second-order sideband generation increases
monotonously with the control field strength. The coupling strength between the
mechanical resonator and the two-level system plays a decisive role in the
appearance of the two-color second-order sidebands. The two-color second-order
sideband generation may provide measurement with higher precision in new degrees
of freedom.
PMID- 29348587
TI - Comparative analyses of fecal microbiota in Chinese isolated Yao population,
minority Zhuang and rural Han by 16sRNA sequencing.
AB - The gut microbiome in humans is associated with geography, diet, lifestyles and
so on, but its relationship with some isolated populations is not clear. We used
the 16sRNA technique to sequence the fecal microbiome in the Chinese isolated Yao
population and compared it with the major minority Zhuang and the major ethnic
Han populations living in the same rural area. Information about diet frequency
and health status and routine serum measurements were collected. The unweighted
UniFrac principal coordinates analysis showed significant structural differences
in fecal microbiota among the three ethnic groups. Statistically significant
differences were observed in the community richness estimator (chaos) and the
diversity estimator (Shannon) among the three groups. At the genus level, the
fecal samples of the isolated Yao population presented the lowest relative
abundance of the Megamonas genus, which was potentially related to the high
frequency of bean consumption in the diet. Two enterotypes were identified in the
overall fecal microbiota in the three populations. In the isolated Yao
population, a higher Bacteroides abundance was observed, but the Prevotella
abundance decreased with increased alcohol consumption.
PMID- 29348589
TI - Novel Miniature Membrane Active Lipopeptidomimetics against Planktonic and
Biofilm Embedded Methicillin-Resistant Staphylococcus aureus.
AB - Escalating multidrug resistance and highly evolved virulence mechanisms have
aggravated the clinical menace of methicillin-resistant Staphylococcus aureus
(MRSA) infections. Towards development of economically viable staphylocidal
agents here we report eight structurally novel tryptophan-arginine template based
peptidomimetics. Out of the designed molecules, three lipopeptidomimetics (S-6, S
7 and S-8) containing 12-amino dodecanoic acid exhibited cell selectivity and
good to potent activity against clinically relevant pathogens MRSA, methicillin
resistant Staphylococcus epidermidis and vancomycin-resistant Enterococcus
faecium (MIC: 1.4-22.7 MUg/mL). Mechanistically, the active peptidomimetics
dissipated membrane potential and caused massive permeabilization on MRSA
concomitant with loss of viability. Against stationary phase MRSA under nutrient
depleted conditions, active peptidomimetics S-7 and S-8 achieved > 6 log
reduction in viability upon 24 h incubation while both S-7 (at 226 MUg/mL) and S
8 (at 28 MUg/mL) also destroyed 48 h mature MRSA biofilm causing significant
decrease in viability (p < 0.05). Encouragingly, most active peptidomimetic S-8
maintained efficacy against MRSA in presence of serum/plasma while exhibiting no
increase in MIC over 17 serial passages at sub-MIC concentrations implying
resistance development to be less likely. Therefore, we envisage that the current
template warrants further optimization towards the development of cell selective
peptidomimetics for the treatment of device associated MRSA infections.
PMID- 29348590
TI - The theoretical molecular weight of NaYF 4 :RE upconversion nanoparticles.
AB - Upconversion nanoparticles (UCNPs) are utilized extensively for biomedical
imaging, sensing, and therapeutic applications, yet the molecular weight of UCNPs
has not previously been reported. Herein, we present a theory based upon the
crystal structure of UCNPs to estimate the molecular weight of UCNPs: enabling
insight into UCNP molecular weight for the first time. We estimate the
theoretical molecular weight of various UCNPs reported in the literature,
predicting that spherical NaYF4 UCNPs ~ 10 nm in diameter will be ~1 MDa (i.e.
106 g/mol), whereas UCNPs ~ 45 nm in diameter will be ~100 MDa (i.e. 108 g/mol).
We also predict that hexagonal crystal phase UCNPs will be of greater molecular
weight than cubic crystal phase UCNPs. Additionally we find that a Gaussian UCNP
diameter distribution will correspond to a lognormal UCNP molecular weight
distribution. Our approach could potentially be generalised to predict the
molecular weight of other arbitrary crystalline nanoparticles: as such, we
provide stand-alone graphic user interfaces to calculate the molecular weight
both UCNPs and arbitrary crystalline nanoparticles. We expect knowledge of UCNP
molecular weight to be of wide utility in biomedical applications where reporting
UCNP quantity in absolute numbers or molarity will be beneficial for inter-study
comparison and repeatability.
PMID- 29348591
TI - Relapsing-Remitting Multiple Sclerosis diagnosis from cerebrospinal fluids via
Fourier transform infrared spectroscopy coupled with multivariate analysis.
AB - Multiple sclerosis (MS) is a chronic, progressive, inflammatory and degenerative
disease of central nervous system. Here, we aimed to develop a method for
differential diagnosis of Relapsing-Remitting MS (RRMS) and clinically isolated
syndrome (CIS) patients, as well as to identify CIS patients who will progress to
RRMS, from cerebrospinal fluid (CSF) by infrared (IR) spectroscopy and
multivariate analysis. Spectral analyses demonstrated significant differences in
the molecular contents, especially in the lipids and Z conformation of DNA of CSF
from CIS, CIS to RRMS transformed (TCIS) and RRMS groups. These changes enables
the discrimination of diseased groups and controls (individuals with no
neurological disease) from each other using hierarchical cluster and principal
component analysis. Some CIS samples were consistently clustered in RRMS class,
which may indicate that these CIS patients potentially will transform to RRMS
over time. Z-DNA band at 795 cm-1 that is existent only in diseased groups and
significant increase in carbonyl amount, decrease in amideI/amide II and
lipid/protein ratios observed only for RRMS groups can be used as diagnostic
biomarkers. The results of the present study shed light on the early diagnosis of
RRMS by IR spectroscopy complemented with multivariate analysis tools.
PMID- 29348592
TI - Stingless Bee Larvae Require Fungal Steroid to Pupate.
AB - The larval stage of the stingless bee Scaptotrigona depilis must consume a
specific brood cell fungus in order to continue development. Here we show that
this fungus is a member of the genus Zygosaccharomyces and provides essential
steroid precursors to the developing bee. Insect pupation requires ecdysteroid
hormones, and as insects cannot synthesize sterols de novo, they must obtain
steroids in their diet. Larval in vitro culturing assays demonstrated that
consuming ergosterol recapitulates the developmental effects on S. depilis as
ingestion of Zygosaccharomyces sp. cells. Thus, we determined the molecular
underpinning of this intimate mutualistic symbiosis. Phylogenetic analyses showed
that similar cases of bee-Zygosaccharomyces symbiosis may exist. This
unprecedented case of bee-fungus symbiosis driven by steroid requirement brings
new perspectives regarding pollinator-microbiota interaction and preservation.
PMID- 29348593
TI - Temporal diabetes-induced biochemical changes in distinctive layers of mouse
retina.
AB - To discover the mechanisms underlying the progression of diabetic retinopathy
(DR), a more comprehensive understanding of the biomolecular processes in
individual retinal cells subjected to hyperglycemia is required. Despite
extensive studies, the changes in the biochemistry of retinal layers during the
development of DR are not well known. In this study, we aimed to determine a more
detailed understanding of the natural history of DR in Akita/+ (type 1 diabetes
model) male mice with different duration of diabetes. Employing label-free
spatially resolved Fourier transform infrared (FT-IR) chemical imaging engaged
with multivariate analysis enabled us to identify temporal-dependent reproducible
biomarkers of the individual retinal layers from mice with 6 weeks,12 weeks, 6
months, and 10 months of age. We report, for the first time, the nature of the
biochemical alterations over time in the biochemistry of distinctive retinal
layers namely photoreceptor retinal layer (PRL), inner nuclear layer (INL), and
plexiform layers (OPL, IPL). Moreover, we present the molecular factors
associated with the changes in the protein structure and cellular lipids of
retinal layers induced by different duration of diabetes. Our paradigm provides a
new conceptual framework for a better understanding of the temporal cellular
changes underlying the progression of DR.
PMID- 29348594
TI - Myelination of Purkinje axons is critical for resilient synaptic transmission in
the deep cerebellar nucleus.
AB - The roles of myelin in maintaining axonal integrity and action potential (AP)
propagation are well established, but its role in synapse maintenance and
neurotransmission remains largely understudied. Here, we investigated how
Purkinje axon myelination regulates synaptic transmission in the Purkinje to deep
cerebellar nuclei (DCN) synapses using the Long Evans Shaker (LES) rat, which
lacks compact myelin and thus displays severe locomotion deficits. DCN neurons
fired spontaneous action potentials (APs), whose frequencies were dependent on
the extent of myelin. In the LES cerebellum with severe myelin deficiency, DCN
neurons were hyper-excitable, exhibiting spontaneous AP firing at a much higher
frequency compared to those from wild type (LE) and heterozygote (LEHet) rats.
The hyper-excitability in LES DCN neurons resulted from reduced inhibitory
GABAergic inputs from Purkinje cells to DCN neurons. Corresponding with
functional alterations including failures of AP propagation, electron microscopic
analysis revealed anatomically fewer active zones at the presynaptic terminals of
Purkinje cells in both LEHet and LES rats. Taken together, these studies suggest
that proper axonal myelination critically regulates presynaptic terminal
structure and function and directly impacts synaptic transmission in the Purkinje
cell-DCN cell synapse in the cerebellum.
PMID- 29348595
TI - On the Angular Distribution of the H+Li2 Cross Sections: a Converged Time
Independent Quantum Scattering Study.
AB - A thorough time-independent quantum scattering study is performed on a benchmark
potential energy surface for the H+Li2 reaction at the fundamental electronic
state. Integral and differential cross sections are calculated along with thermal
rate coefficients until convergence is reached. Our findings show that
vibrational and rotational excitations of the reactant hinder reactivity, though
for the latter a considerable reaction promotion was spotted as we increase the
reactant rotational quantum number until the critical value of j = 4. Such a
promotion then begins to retract, eventually becoming an actual inhibition for
larger j. In a straightforward manner, the concept of time-independent methods
implemented in this study allowed this accurate state-to-state analysis.
Furthermore, a nearly isotropic behaviour of the scattering is noted to take
place from the angular point of view. Remarkably, our computational protocol is
ideally suited to yield converged thermal rate coefficients, revealing a non
Arrhenius pattern and showing that J-shifting approach fails to describe this
particular reaction. Our results, when compared to previous and independent ones,
reinforce the latest theoretical reference for future validation in the
experimental field.
PMID- 29348596
TI - Dynamics of Tree Species Diversity in Unlogged and Selectively Logged Malaysian
Forests.
AB - Selective logging that is commonly conducted in tropical forests may change tree
species diversity. In rarely disturbed tropical forests, locally rare species
exhibit higher survival rates. If this non-random process occurs in a logged
forest, the forest will rapidly recover its tree species diversity. Here we
determined whether a forest in the Pasoh Forest Reserve, Malaysia, which was
selectively logged 40 years ago, recovered its original species diversity
(species richness and composition). To explore this, we compared the dynamics of
secies diversity between unlogged forest plot (18.6 ha) and logged forest plot
(5.4 ha). We found that 40 years are not sufficient to recover species diversity
after logging. Unlike unlogged forests, tree deaths and recruitments did not
contribute to increased diversity in the selectively logged forests. Our results
predict that selectively logged forests require a longer time at least than our
observing period (40 years) to regain their diversity.
PMID- 29348597
TI - Author Correction: Short-Course, High-Dose Rifampicin Achieves Wolbachia
Depletion Predictive of Curative Outcomes in Preclinical Models of Lymphatic
Filariasis and Onchocerciasis.
AB - A correction to this article has been published and is linked from the HTML
version of this paper. The error has been fixed in the paper.
PMID- 29348598
TI - Increased diversity with reduced "diversity evenness" of tumor infiltrating T
cells for the successful cancer immunotherapy.
AB - To facilitate the optimization of cancer immunotherapy lacking immune-related
adverse events, we performed TCR repertoire analysis of tumor-infiltrating CD8+ T
cells in B16 melanoma-bearing mice receiving anti-PD-1, anti-CTLA-4, anti-4-1BB,
anti-CD4 or a combination of anti-PD-1 and 4-1BB antibodies. Although CD8+ T
cells in the tumor were activated and expanded to a greater or lesser extent by
these therapies, tumor growth suppression was achieved only by anti-PD-1, anti-PD
1/4-1BB combined, or by anti-CD4 treatment, but not by anti-CTLA-4 or anti-4-1BB
monotherapy. Increased CD8+ T cell effector function and TCR diversity with
enrichment of certain TCR clonotypes in the tumor was associated with anti-tumor
effects. In contrast, polyclonal activation of T-cells in the periphery was
associated with tissue damage. Thus, optimal combination therapy increases TCR
diversity with extended activation of selective CD8+ T-cells specifically in the
tumor but not in the periphery. Incorporation of the concept of evenness for the
TCR diversity is proposed.
PMID- 29348599
TI - In situ formation of artificial moth-eye structure by spontaneous nano-phase
separation.
AB - Unprecedented in situ formation of artificial moth-eye structure is demonstrated
by spontaneous nano-phase separation of a silica-based system on substrate. The
moth-eye thin film with a homogenously distributed nipples array shows broadband
antireflection functionalities. The mechanism of nano-phase separation is
unveiled as spinodal decomposition by chemical freezing method and thermodynamic
analysis. The current method may provide a new avenue to ready fabrication of
patterned nanostructures toward a variety of applications.
PMID- 29348600
TI - Chinese olive extract ameliorates hepatic lipid accumulation in vitro and in vivo
by regulating lipid metabolism.
AB - Chinese olive contains plenty of polyphenols, which possess a wide range of
biological actions. In this study, we aimed to investigate the role of the ethyl
acetate fraction of Chinese olive fruit extract (CO-EtOAc) in the modulation of
lipid accumulation in vitro and in vivo. In cellular studies, CO-EtOAc attenuated
oleic acid-induced lipid accumulation; we then elucidated the molecular
mechanisms of CO-EtOAc in FL83B mouse hepatocytes. CO-EtOAc suppressed the mRNA
levels of fatty acid transporter genes (CD36 and FABP) and lipogenesis genes
(SREBP-1c, FAS, and ACC1), but upregulated genes that govern lipolysis (HSL) and
lipid oxidation (PPARalpha, CPT-1, and ACOX). Moreover, CO-EtOAc increased the
protein expression of phosphorylated AMPK, ACC1, CPT-1, and PPARalpha, but
downregulated the expression of mature SREBP-1c and FAS. AMPK plays an essential
role in CO-EtOAc-mediated amelioration of lipid accumulation. Furthermore, we
confirmed that CO-EtOAc significantly inhibited body weight gain, epididymal
adipose tissue weight, and hepatic lipid accumulation via regulation of the
expression of fatty acid transporter, lipogenesis, and fatty acid oxidation genes
and proteins in C57BL/6 mice fed a 60% high-fat diet. Therefore, Chinese olive
fruits may have the potential to improve the metabolic abnormalities associated
with fatty liver under high fat challenge.
PMID- 29348601
TI - Exclusion from spheroid formation identifies loss of essential cell-cell adhesion
molecules in colon cancer cells.
AB - Many cell lines derived from solid cancers can form spheroids, which recapitulate
tumor cell clusters and are more representative of the in vivo situation than 2D
cultures. During spheroid formation, a small proportion of a variety of different
colon cancer cell lines did not integrate into the sphere and lost cell-cell
adhesion properties. An enrichment protocol was developed to augment the
proportion of these cells to 100% purity. The basis for the separation of
spheroids from non-spheroid forming (NSF) cells is simple gravity-sedimentation.
This protocol gives rise to sub-populations of colon cancer cells with stable
loss of cell-cell adhesion. SW620 cells lacked E-cadherin, DLD-1 cells lost alpha
catenin and HCT116 cells lacked P-cadherin in the NSF state. Knockdown of these
molecules in the corresponding spheroid-forming cells demonstrated that loss of
the respective proteins were indeed responsible for the NSF phenotypes. Loss of
the spheroid forming phenotype was associated with increased migration and
invasion properties in all cell lines tested. Hence, we identified critical
molecules involved in spheroid formation in different cancer cell lines. We
present here a simple, powerful and broadly applicable method to generate new
sublines of tumor cell lines to study loss of cell-cell adhesion in cancer
progression.
PMID- 29348602
TI - The ten-year evolutionary trajectory of a highly recurrent paediatric high grade
neuroepithelial tumour with MN1:BEND2 fusion.
AB - Astroblastomas are rare brain tumours which predominate in children and young
adults, and have a controversial claim as a distinct entity, with no established
WHO grade. Reports suggest a better outcome than high grade gliomas, though they
frequently recur. Recently, they have been described to overlap with a newly
discovered group of tumours described as'high grade neuroepithelial tumour with
MN1 alteration' (CNS HGNET-MN1), defined by global methylation patterns and
strongly associated with gene fusions targeting MN1. We have studied a unique
case of astroblastoma arising in a 6 year-old girl, with multiple recurrences
over a period of 10 years, with the pathognomonic MN1:BEND2 fusion. Exome
sequencing allowed for a phylogenetic reconstruction of tumour evolution, which
when integrated with clinical, pathological and radiological data provide for a
detailed understanding of disease progression, with initial treatment driving
tumour dissemination along four distinct trajectories. Infiltration of distant
sites was associated with a later genome doubling, whilst there was evidence of
convergent evolution of different lesions acquiring distinct alterations
targeting NF-kappaB. These data represent an unusual opportunity to understand
the evolutionary history of a highly recurrent childhood brain tumour, and
provide novel therapeutic targets for astroblastoma/CNS HGNET-MN1.
PMID- 29348603
TI - Comprehensive list of SUMO targets in Caenorhabditis elegans and its implication
for evolutionary conservation of SUMO signaling.
AB - Post-translational modification by small ubiquitin-related modifier (SUMO) is a
key regulator of cell physiology, modulating protein-protein and protein-DNA
interactions. Recently, SUMO modifications were postulated to be involved in
response to various stress stimuli. We aimed to identify the near complete set of
proteins modified by SUMO and the dynamics of the modification in stress
conditions in the higher eukaryote, Caenorhabditis elegans. We identified 874
proteins modified by SUMO in the worm. We have analyzed the SUMO modification in
stress conditions including heat shock, DNA damage, arsenite induced cellular
stress, ER and osmotic stress. In all these conditions the global levels of
SUMOylation was significantly increased. These results show the evolutionary
conservation of SUMO modifications in reaction to stress. Our analysis showed
that SUMO targets are highly conserved throughout species. By comparing the SUMO
targets among species, we approximated the total number of proteins modified in a
given proteome to be at least 15-20%. We developed a web server designed for
convenient prediction of potential SUMO modification based on experimental
evidences in other species.
PMID- 29348605
TI - Co-selected mutations in VCP: a novel mechanism of resistance to VCP inhibitors.
PMID- 29348604
TI - Cromolyn Reduces Levels of the Alzheimer's Disease-Associated Amyloid beta
Protein by Promoting Microglial Phagocytosis.
AB - Amyloid-beta protein (Abeta) deposition is a pathological hallmark of Alzheimer's
disease (AD). Abeta deposition triggers both pro-neuroinflammatory microglial
activation and neurofibrillary tangle formation. Cromolyn sodium is an asthma
therapeutic agent previously shown to reduce Abeta levels in transgenic AD mouse
brains after one-week of treatment. Here, we further explored these effects as
well as the mechanism of action of cromolyn, alone, and in combination with
ibuprofen in APPSwedish-expressing Tg2576 mice. Mice were treated for 3 months
starting at 5 months of age, when the earliest stages of beta-amyloid deposition
begin. Cromolyn, alone, or in combination with ibuprofen, almost completely
abolished longer insoluble Abeta species, i.e. Abeta40 and Abeta42, but increased
insoluble Abeta38 levels. In addition to its anti-aggregation effects on Abeta,
cromolyn, alone, or plus ibuprofen, but not ibuprofen alone, increased microglial
recruitment to, and phagocytosis of beta-amyloid deposits in AD mice. Cromolyn
also promoted Abeta42 uptake in microglial cell-based assays. Collectively, our
data reveal robust effects of cromolyn, alone, or in combination with ibuprofen,
in reducing aggregation-prone Abeta levels and inducing a neuroprotective
microglial activation state favoring Abeta phagocytosis versus a pro
neuroinflammatory state. These findings support the use of cromolyn, alone, or
with ibuprofen, as a potential AD therapeutic.
PMID- 29348606
TI - AMP-activated protein kinase agonist N6-(3-hydroxyphenyl)adenosine protects
against fulminant hepatitis by suppressing inflammation and apoptosis.
AB - Both AMP-activated protein kinase (AMPK) agonist and inhibitor have been reported
to protect against fulminant hepatitis, implying that AMPK may play a complicated
role in the development of fulminant hepatitis. In this study, we exploited
whether the novel AMPK agonist N6-(3-hydroxyphenyl)adenosine (named as M1)
exerted protective effects on fulminant hepatitis and whether its beneficial
effects were AMPK-dependent. Results showed that intraperitoneal injection of M1
improved liver function, ameliorated liver injury and finally raised the survival
rate in D-galactosamine/lipopolysaccharide (GalN/LPS)-treated mice. These
beneficial effects of M1 may attribute to the suppression of pro-inflammatory
cytokines production and the prevention of hepatocyte apoptosis. Furthermore, M1
pretreatment mitigated LPS-stimulated TLR4 expression and NFkappaB activation in
murine peritoneal macrophages and prevented actinomycin D (Act D)/tumor necrosis
factor alpha (TNFalpha)-induced apoptosis by promoting protective autophagy in
primary hepatocytes. Additionally, M1-induced AMPK activation was responsible
both for its anti-inflammatory action in macrophages and for its anti-apoptotic
action in hepatocytes. To our surprise, compared with the control
AMPKalpha1lox/lox/AMPKalpha2lox/lox mice, liver-specific AMPKalpha1 knockout
(AMPKalpha1LS-/-) mice were more sensitive to GalN/LPS administration but not
AMPKalpha2LS-/-mice, and the beneficial effects of M1 on acute liver failure and
the production of pro-inflammatory factors were dampened in AMPKalpha1LS-/- mice.
Therefore, our study may prove that M1 could be a promising therapeutic agent for
fulminant hepatitis, and targeting AMPK may be useful therapeutically in the
control of LPS-induced hepatotoxicity.
PMID- 29348607
TI - Evaluation of mitochondrial bioenergetics, dynamics, endoplasmic reticulum
mitochondria crosstalk, and reactive oxygen species in fibroblasts from patients
with complex I deficiency.
AB - Mitochondrial complex I (CI) deficiency is the most frequent cause of oxidative
phosphorylation (OXPHOS) disorders in humans. In order to benchmark the effects
of CI deficiency on mitochondrial bioenergetics and dynamics, respiratory chain
(RC) and endoplasmic reticulum (ER)-mitochondria communication, and superoxide
production, fibroblasts from patients with mutations in the ND6, NDUFV1 or ACAD9
genes were analyzed. Fatty acid metabolism, basal and maximal respiration,
mitochondrial membrane potential, and ATP levels were decreased. Changes in
proteins involved in mitochondrial dynamics were detected in various combinations
in each cell line, while variable changes in RC components were observed. ACAD9
deficient cells exhibited an increase in RC complex subunits and DDIT3, an ER
stress marker. The level of proteins involved in ER-mitochondria communication
was decreased in ND6 and ACAD9 deficient cells. |DeltaPsi| and cell viability
were further decreased in all cell lines. These findings suggest that disruption
of mitochondrial bioenergetics and dynamics, ER-mitochondria crosstalk, and
increased superoxide contribute to the pathophysiology in patients with ACAD9
deficiency. Furthermore, treatment of ACAD9 deficient cells with JP4-039, a novel
mitochondria-targeted reactive oxygen species, electron and radical scavenger,
decreased superoxide level and increased basal and maximal respiratory rate,
identifying a potential therapeutic intervention opportunity in CI deficiency.
PMID- 29348608
TI - Phytase overexpression in Arabidopsis improves plant growth under osmotic stress
and in combination with phosphate deficiency.
AB - Engineering osmotolerant plants is a challenge for modern agriculture. An
interaction between osmotic stress response and phosphate homeostasis has been
reported in plants, but the identity of molecules involved in this interaction
remains unknown. In this study we assessed the role of phytic acid (PA) in
response to osmotic stress and/or phosphate deficiency in Arabidopsis thaliana.
For this purpose, we used Arabidopsis lines (L7 and L9) expressing a bacterial
beta-propeller phytase PHY-US417, and a mutant in inositol polyphosphate kinase 1
gene (ipk1-1), which were characterized by low PA content, 40% (L7 and L9) and
83% (ipk1-1) of the wild-type (WT) plants level. We show that the PHY
overexpressor lines have higher osmotolerance and lower sensitivity to abscisic
acid than ipk1-1 and WT. Furthermore, PHY-overexpressors showed an increase by
more than 50% in foliar ascorbic acid levels and antioxidant enzyme activities
compared to ipk1-1 and WT plants. Finally, PHY-overexpressors are more tolerant
to combined mannitol stresses and phosphate deficiency than WT plants. Overall,
our results demonstrate that the modulation of PA improves plant growth under
osmotic stress, likely via stimulation of enzymatic and non-enzymatic antioxidant
systems, and that beside its regulatory role in phosphate homeostasis, PA may be
also involved in fine tuning osmotic stress response in plants.
PMID- 29348609
TI - Effects of vitamin D supplementation on inflammatory markers in heart failure: a
systematic review and meta-analysis of randomized controlled trials.
AB - Vitamin D is reported to have anti-inflammatory properties; however the effects
of vitamin D supplementation on inflammation in patients with heart failure (HF)
have not been established. We performed a systematic review and meta-analysis
examining effects of vitamin D supplementation on inflammatory markers in
patients with HF. MEDLINE, CINAHL, EMBASE, All EBM, and Clinical Trials
registries were systematically searched for RCTs from inception to 25 January
2017. Two independent reviewers screened all full text articles (no date or
language limits) for RCTs reporting effects of vitamin D supplementation (any
form, route, duration, and co-supplementation) compared with placebo or usual
care on inflammatory markers in patients with heart failure. Two reviewers
assessed risk of bias and quality using the grading of recommendations,
assessment, development, and evaluation approach. Seven studies met inclusion
criteria and six had data available for pooling (n = 1012). In meta-analyses,
vitamin D-supplemented groups had lower concentrations of tumor necrosis factor
alpha (TNF-alpha) at follow-up compared with controls (n = 380; p = 0.04). There
were no differences in C-reactive protein (n = 231), interleukin (IL)-10 (n =
247) or IL-6 (n = 154) between vitamin D and control groups (all p > 0.05). Our
findings suggest that vitamin D supplementation may have specific, but modest
effects on inflammatory markers in HF.
PMID- 29348610
TI - The histone methyltransferase DOT1L inhibits osteoclastogenesis and protects
against osteoporosis.
AB - Osteoclasts are absorptive cells that play a critical role in homeostatic bone
remodeling and pathological bone resorption. Emerging evidence suggests an
important role of epigenetic regulation in osteoclastogenesis. In this study, we
investigated the role of DOT1L, which regulates gene expression epigenetically by
histone H3K79 methylation (H3K79me), during osteoclast formation. Using RANKL
induced RAW264.7 macrophage cells as an osteoclast differentiation model, we
found that DOT1L and H3K79me2 levels were upregulated during osteoclast
differentiation. Small molecule inhibitor- (EPZ5676 or EPZ004777) or short
hairpin RNA-mediated reduction in DOT1L expression promoted osteoclast
differentiation and resorption. In addition, DOT1L inhibition increased
osteoclast surface area and accelerated bone-mass reduction in a mouse
ovariectomy (OVX) model of osteoporosis without alter osteoblast differentiation.
DOT1L inhibition increase reactive oxygen species (ROS) generation and autophagy
activity, and cell migration in pre-osteoclasts. Moreover, it strengthened
expression of osteoclast fusion and resorption-related protein CD9 and MMP9 in
osteoclasts derived from RAW264.7. Our findings support a new mechanism of DOT1L
regulated, H3K79me2-mediated, epigenetic regulation of osteoclast
differentiation, implicating DOT1L as a new therapeutic target for osteoclast
dysregulation-induced disease.
PMID- 29348611
TI - Prediction is Production: The missing link between language production and
comprehension.
AB - Language comprehension often involves the generation of predictions. It has been
hypothesized that such prediction-for-comprehension entails actual language
production. Recent studies provided evidence that the production system is
recruited during language comprehension, but the link between production and
prediction during comprehension remains hypothetical. Here, we tested this
hypothesis by comparing prediction during sentence comprehension (primary task)
in participants having the production system either available or not (non-verbal
versus verbal secondary task). In the primary task, sentences containing an
expected or unexpected target noun-phrase were presented during
electroencephalography recording. Prediction, measured as the magnitude of the
N400 effect elicited by the article (expected versus unexpected), was hindered
only when the production system was taxed during sentence context reading. The
present study provides the first direct evidence that the availability of the
speech production system is necessary for generating lexical prediction during
sentence comprehension. Furthermore, these important results provide an
explanation for the recruitment of language production during comprehension.
PMID- 29348613
TI - Solar system expansion and strong equivalence principle as seen by the NASA
MESSENGER mission.
AB - The NASA MESSENGER mission explored the innermost planet of the solar system and
obtained a rich data set of range measurements for the determination of Mercury's
ephemeris. Here we use these precise data collected over 7 years to estimate
parameters related to general relativity and the evolution of the Sun. These
results confirm the validity of the strong equivalence principle with a
significantly refined uncertainty of the Nordtvedt parameter eta = (-6.6 +/- 7.2)
* 10-5. By assuming a metric theory of gravitation, we retrieved the post
Newtonian parameter beta = 1 + (-1.6 +/- 1.8) * 10-5 and the Sun's gravitational
oblateness, [Formula: see text] = (2.246 +/- 0.022) * 10-7. Finally, we obtain an
estimate of the time variation of the Sun gravitational parameter, [Formula: see
text] = (-6.13 +/- 1.47) * 10-14, which is consistent with the expected solar
mass loss due to the solar wind and interior processes. This measurement allows
us to constrain [Formula: see text] to be <4 * 10-14 per year.
PMID- 29348612
TI - GWAS in childhood acute lymphoblastic leukemia reveals novel genetic associations
at chromosomes 17q12 and 8q24.21.
AB - Childhood acute lymphoblastic leukemia (ALL) (age 0-14 years) is 20% more common
in Latino Americans than non-Latino whites. We conduct a genome-wide association
study in a large sample of 3263 Californian children with ALL (including 1949 of
Latino heritage) and 3506 controls matched on month and year of birth, sex, and
ethnicity, and an additional 12,471 controls from the Kaiser Resource for Genetic
Epidemiology Research on Aging Cohort. Replication of the strongest genetic
associations is performed in two independent datasets from the Children's
Oncology Group and the California Childhood Leukemia Study. Here we identify new
risk loci on 17q12 near IKZF3/ZPBP2/GSDMB/ORMDL3, a locus encompassing a
transcription factor important for lymphocyte development (IKZF3), and at an 8q24
region known for structural contacts with the MYC oncogene. These new risk loci
may impact gene expression via local (four 17q12 genes) or long-range (8q24)
interactions, affecting function of well-characterized hematopoietic and growth
regulation pathways.
PMID- 29348614
TI - Noise-induced bistability in the fate of cancer phenotypic quasispecies: a bit
strings approach.
AB - Tumor cell populations are highly heterogeneous. Such heterogeneity, both at
genotypic and phenotypic levels, is a key feature during tumorigenesis. How to
investigate the impact of this heterogeneity in the dynamics of tumors cells
becomes an important issue. Here we explore a stochastic model describing the
competition dynamics between a pool of heterogeneous cancer cells with distinct
phenotypes and healthy cells. This model is used to explore the role of
demographic fluctuations on the transitions involving tumor clearance. Our
results show that for large population sizes, when demographic fluctuations are
negligible, there exists a sharp transition responsible for tumor cells
extinction at increasing tumor cells' mutation rates. This result is consistent
with a mean field model developed for the same system. The mean field model
reveals only monostability scenarios, in which either the dominance of the tumor
cells or the dominance of the healthy cells is found. Interestingly, the
stochastic model shows that for small population sizes the monostability behavior
disappears, involving the presence of noise-induced bistability. The impact of
the initial populations of cells in the fate of the cell populations is
investigated, as well as the transient times towards the healthy and the cancer
states.
PMID- 29348615
TI - Nucleation and Ostwald Growth of Particles in Fe-O-Al-Ca Melt.
AB - Tremendous focus has been put on the control of particle size distribution which
effects the grain structure and mechanical properties of resulting metallic
materials, and thus nucleation and growth of particles in solution should be
clarified. This study uses classical nucleation theory and Ostwald ripening
theory to probe the relationship between the compositions of Fe-O-Al-Ca melts and
the behavior of particles under the condition of no external stirring. Our
experimental data suggest that decreasing the initial Ca addition and Al addition
is conductive to the increase of nucleation rate for calcium aluminate particles,
which exhibits a same change trend with that predicted from classical nucleation
theory. Based on the experimental evidence for particles size distribution in
three-dimensional, we demonstrate that Ostwald ripening is the predominate
mechanism on the coarsening of particles in Fe-O-Al-Ca melt at early stage of
deoxidation under the condition of no external stirring but not at later stage.
PMID- 29348616
TI - Fast and effective mitochondrial delivery of omega-Rhodamine-B-polysulfobetaine
PEG copolymers.
AB - Mitochondrial targeting and entry, two crucial steps in fighting severe diseases
resulting from mitochondria dysfunction, pose important challenges in current
nanomedicine. Cell-penetrating peptides or targeting groups, such as Rhodamine-B
(Rho), are known to localize in mitochondria, but little is known on how to
enhance their effectiveness through structural properties of polymeric carriers.
To address this issue, we prepared 8 copolymers of 3
dimethyl(methacryloyloxyethyl)ammonium propane sulfonate and poly(ethyleneglycol)
methacrylate, p(DMAPS-ran-PEGMA) (molecular weight, 18.0 < M n < 74.0 kg/mol)
with two different endgroups. We labeled them with Rho groups attached along the
chain or on one of the two endgroups (alpha or omega). From studies by flow
cytometry and confocal fluorescence microscopy of the copolymers internalization
in HeLa cells in the absence and presence of pharmacological inhibitors, we
established that the polymers cross the cell membrane foremost by translocation
and also by endocytosis, primarily clathrin-dependent endocytosis. The most
effective mitochondrial entry was achieved by copolymers of M n < 30.0 kg/mol,
lightly grafted with PEG chains (< 5 mol %) labeled with Rho in the omega
position. Our findings may be generalized to the uptake and mitochondrial
targeting of prodrugs and imaging agents with a similar polymeric scaffold.
PMID- 29348617
TI - Neuronal lysosomal dysfunction releases exosomes harboring APP C-terminal
fragments and unique lipid signatures.
AB - Defects in endolysosomal and autophagic functions are increasingly viewed as key
pathological features of neurodegenerative disorders. A master regulator of these
functions is phosphatidylinositol-3-phosphate (PI3P), a phospholipid synthesized
primarily by class III PI 3-kinase Vps34. Here we report that disruption of
neuronal Vps34 function in vitro and in vivo impairs autophagy, lysosomal
degradation as well as lipid metabolism, causing endolysosomal membrane damage.
PI3P deficiency also promotes secretion of unique exosomes enriched for
undigested lysosomal substrates, including amyloid precursor protein C-terminal
fragments (APP-CTFs), specific sphingolipids, and the phospholipid
bis(monoacylglycero)phosphate (BMP), which normally resides in the internal
vesicles of endolysosomes. Secretion of these exosomes requires neutral
sphingomyelinase 2 and sphingolipid synthesis. Our results reveal a homeostatic
response counteracting lysosomal dysfunction via secretion of atypical exosomes
eliminating lysosomal waste and define exosomal APP-CTFs and BMP as candidate
biomarkers for endolysosomal dysfunction associated with neurodegenerative
disorders.
PMID- 29348618
TI - Epigallocatechin gallate (EGCG) reduces the intensity of pancreatic amyloid
fibrils in human islet amyloid polypeptide (hIAPP) transgenic mice.
AB - The formation of amyloid fibrils by human islet amyloid polypeptide protein
(hIAPP) has been implicated in pancreas dysfunction and diabetes. However,
efficient treatment options to reduce amyloid fibrils in vivo are still lacking.
Therefore, we tested the effect of epigallocatechin gallate (EGCG) on fibril
formation in vitro and in vivo. To determine the binding of hIAPP and EGCG, in
vitro interaction studies were performed. To inhibit amyloid plaque formation in
vivo, homozygous (tg/tg), hemizygous (wt/tg), and control mice (wt/wt) were
treated with EGCG. EGCG bound to hIAPP in vitro and induced formation of
amorphous aggregates instead of amyloid fibrils. Amyloid fibrils were detected in
the pancreatic islets of tg/tg mice, which was associated with disrupted islet
structure and diabetes. Although pancreatic amyloid fibrils could be detected in
wt/tg mice, these animals were non-diabetic. EGCG application decreased amyloid
fibril intensity in wt/tg mice, however it was ineffective in tg/tg animals. Our
data indicate that EGCG inhibits amyloid fibril formation in vitro and reduces
fibril intensity in non-diabetic wt/tg mice. These results demonstrate a possible
in vivo effectiveness of EGCG on amyloid formation and suggest an early
therapeutical application.
PMID- 29348619
TI - Cytokine-mediated changes in K+ channel activity promotes an adaptive Ca2+
response that sustains beta-cell insulin secretion during inflammation.
AB - Cytokines present during low-grade inflammation contribute to beta-cell
dysfunction and diabetes. Cytokine signaling disrupts beta-cell glucose
stimulated Ca2+ influx (GSCI) and endoplasmic reticulum (ER) Ca2+ ([Ca2+]ER)
handling, leading to diminished glucose-stimulated insulin secretion (GSIS).
However, cytokine-mediated changes in ion channel activity that alter beta-cell
Ca2+ handling remain unknown. Here we investigated the role of K+ currents in
cytokine-mediated beta-cell dysfunction. Kslow currents, which control the
termination of intracellular Ca2+ ([Ca2+]i) oscillations, were reduced following
cytokine exposure. As a consequence, [Ca2+]i and electrical oscillations were
accelerated. Cytokine exposure also increased basal islet [Ca2+]i and decreased
GSCI. The effect of cytokines on TALK-1 K+ currents were also examined as TALK-1
mediates Kslow by facilitating [Ca2+]ER release. Cytokine exposure decreased
KCNK16 transcript abundance and associated TALK-1 protein expression, increasing
[Ca2+]ER storage while maintaining 2nd phase GSCI and GSIS. This adaptive Ca2+
response was absent in TALK-1 KO islets, which exhibited decreased 2nd phase GSCI
and diminished GSIS. These findings suggest that Kslow and TALK-1 currents play
important roles in altered beta-cell Ca2+ handling and electrical activity during
low-grade inflammation. These results also reveal that a cytokine-mediated
reduction in TALK-1 serves an acute protective role in beta-cells by facilitating
increased Ca2+ content to maintain GSIS.
PMID- 29348620
TI - A vacuolar sorting receptor-independent sorting mechanism for storage vacuoles in
soybean seeds.
AB - The seed storage proteins of soybean (Glycine max) are composed mainly of
glycinin (11S globulin) and beta-conglycinin (7S globulin). The subunits of
glycinin (A1aB1b, A1bB2, A2B1a, A3B4, and A5A4B3) are synthesized as a single
polypeptide precursor. These precursors are assembled into trimers with a random
combination of subunits in the endoplasmic reticulum, and are sorted to the
protein storage vacuoles. Proteins destined for transport to protein storage
vacuoles possess a vacuolar sorting determinant, and in this regard, the A1aB1b
subunit contains a C-terminal peptide that is sufficient for its sorting to
protein storage vacuoles. The A3B4 subunit, however, lacks a corresponding C
terminal sorting determinant. In this study, we found that, unlike the A1aB1b
subunit, the A3B4 subunit does not bind to previously reported vacuolar sorting
receptors. Despite this difference, we observed that the A3B4 subunit is sorted
to protein storage vacuoles in a transgenic soybean line expressing the A3B4
subunit of glycinin. These results indicate that a protein storage vacuolar
sorting mechanism that functions independently of the known vacuolar sorting
receptors in seeds might be present in soybean seeds.
PMID- 29348621
TI - Dynamic cellular maps of molecular species: Application to drug-target
interactions.
AB - The design of living cell studies aimed at deciphering the mechanism of action of
drugs targeting proteins with multiple functions, expressed in a wide range of
concentrations and cellular locations, is a real challenge. We recently showed
that the antitumor drug plitidepsin (APL) localizes sufficiently close to the
elongation factor eEF1A2 so as to suggest the formation of drug-protein complexes
in living cells. Here we present an extension of our previous micro-spectroscopy
study, that combines Generalized Polarization (GP) images, with the phasor
approach and fluorescence lifetime imaging microscopy (FLIM), using a 7
aminocoumarin drug analog (APL*) as fluorescence tracer. Using the proposed
methodology, we were able to follow in real time the formation and relative
distribution of two sets of APL-target complexes in live cells, revealing two
distinct patterns of behavior for HeLa-wt and APL resistant HeLa-APL-R cells. The
information obtained may complement and facilitate the design of new experiments
and the global interpretation of the results obtained with other biochemical and
cell biology methods, as well as possibly opening new avenues of study to
decipher the mechanism of action of new drugs.
PMID- 29348622
TI - A novel method of utilizing skinfolds and bioimpedance for determining body fat
percentage via a field-based three-compartment model.
AB - BACKGROUND/OBJECTIVES: The purpose was to determine if skinfolds (SF) and
bioelectrical impedance analysis (BIA) could provide accurate estimates of body
volume (BV) and total body water (TBW), respectively, for use in a 3-compartment
(3-C) model to estimate percent body fat (BF%) when compared to laboratory
derived measures. SUBJECTS/METHODS: A sample of sixty-four men (age = 22.9 +/-
5.4 years) and 59 women (age = 21.6 +/- 4.3 years) participated in the study.
Laboratory 3-C (3CLAB) model BF% was determined with underwater weighing for body
volume (BV) and bioimpedance spectroscopy for total body water (TBW). The 3-C
field (3CFIELD) estimates of BF% included BV from the 7-site SF technique and TBW
from hand-to-foot BIA. RESULTS: A significant difference in BF% (p < 0.01) was
found between the 3CLAB and 3CFIELD in the entire sample and within the men, but
the effect sizes (ES) were small (0.09 and 0.17, respectively). The difference
between means was not significant in the women (ES = 0.05, p = 0.332). Compared
to the 3CLAB, the total error (TE) ranged 2.2-2.4% for 3CFIELD, 5.7-5.8% for SF,
and 4.0-4.6% for BIA. CONCLUSIONS: The findings suggest that BV and TBW derived
from SF and BIA, respectively, can be used in a 3CFIELD model to increase the
accuracy of BF% estimates over SF and BIA alone.
PMID- 29348623
TI - Fetal vitamin D concentration and growth, adiposity and neurodevelopment during
infancy.
AB - BACKGROUND/OBJECTIVES: To determine the association between cord blood 25
hydroxyvitamin D (25(OH)D) concentration with growth, adiposity and
neurodevelopment during infancy. SUBJECTS/METHODS: Serum 25(OH)D was measured in
cord blood by the liquid chromatography tandem mass spectrometry (LC-MS/MS) from
the Shanghai's "Allergy and Obesity Cohort study" (n = 1244). Weight, length,
head circumference, and body mass index (BMI) z-scores for age were calculated
based on World Health Organization Standard (at 6 months, 1 years, and 2 years).
Neurodevelopment was measured at 2 years using Ages and Stages Questionnaire.
Generalized estimating equation and multivariable logistic regression model were
exploited to examine associations between fetal 25(OH)D concentration and
offspring outcomes. RESULTS: The median of the 25(OH)D concentration in cord
blood was 22.4 ng/ml (interquartile range, 27.3-8.6). Infants born in winter had
lower 25(OH)D concentration. 25(OH)D deficiency was not associated with weight z
score (mean difference, 0.07; 95% confidence internal (CI), -0.09 to 0.23),
length z-score (mean difference, 0.01; 95% CI, -0.19 to 0.21), head circumference
z-score (mean difference, -0.06; 95% CI, -0.27 to 0.15) and BMI z-score (mean
difference, 0.09; 95% CI, -0.07 to 0.25) or neurodevelopment during infancy,
adjusting for sex, socio-economic position, pre-pregnancy maternal BMI, and
maternal and neonatal characteristics. The associations did not vary by gender. A
sensitivity analysis of available case analysis showed virtually the same
results. CONCLUSIONS: Fetal vitamin D concentration was not associated with
growth, adiposity or neurodevelopment during infancy. The role of vitamin D
concentration and its mechanistic pathway in the early origins of adiposity needs
to be clarified.
PMID- 29348624
TI - Soy food and isoflavone intake reduces the risk of cognitive impairment in
elderly Japanese women.
AB - Data were derived from the National Institute for Longevity Sciences-Longitudinal
Study of Aging. Subjects comprised 403 men and 373 women aged 60-81 years at
baseline who participated in the follow-up study at least once. Bean, soy product
and soy isoflavone intake was assessed using a 3-day dietary record at baseline.
Cognitive function was assessed by the Mini-Mental State Examination (MMSE). MMSE
scores of <=23 were used to define cognitive impairment. The relationship between
bean, soy product and soy isoflavone intake and cognitive impairment was assessed
using a generalized estimating equation. Multivariate-adjusted odds ratios (95%
confidence intervals) for cognitive impairment with a 1 s.d. increase in total
bean, total soybean and total soy isoflavone intakes were 0.48 (0.28-0.81; p =
0.006), 0.51 (0.32-0.83; p = 0.007), and 0.55 (0.32-0.93; p = 0.026),
respectively, in women. Total soybean and soy isoflavone intake might decrease
the risk of cognitive impairment in elderly Japanese women.
PMID- 29348625
TI - Universal type/subtype-specific antibodies for quantitative analyses of
neuraminidase in trivalent influenza vaccines.
AB - Both influenza viral hemagglutinin and neuraminidase can induce protective immune
responses in humans. Although the viral hemagglutinin antigens have been
quantified in influenza vaccines, the amounts of neuraminidase remain
undetermined. Using comprehensive bioinformatics analyses of all neuraminidase
sequences, we identified highly conserved and subtype-specific peptide epitopes
within each of N1, N2 and type B neuraminidase groups. Mono-specific antibodies
generated against these peptides bound to their respective subtype/type only
while demonstrating remarkable specificity against the viral neuraminidase
sequences without any cross-reactivity with allantoic and cellular proteins.
Moreover, the subtype/type-specific antibodies were found not to interfere with
one another when a mixture of vaccine samples was analysed. Importantly,
immunoassay based on these antibodies can quantitatively determine neuraminidase
in commercial trivalent vaccine samples. Analyses of vaccines from eight
manufacturers using the same vaccine seeds revealed significant differences in
neuraminidase levels. Specifically, while the ratio between neuraminidase and
hemagglutinin in some products are found to be close 1/5, other products have a
ratio of approximately 1/100, a level which is far below the theoretical ratio
between neuraminidase and hemagglutinin in a virus. The antibody-based assays
reported here could be of great value for better quality control of both
monovalent and trivalent vaccines.
PMID- 29348626
TI - Arabidopsis serine/threonine/tyrosine protein kinase phosphorylates oil body
proteins that regulate oil content in the seeds.
AB - Protein phosphorylation is an important post-translational modification that can
regulate the protein function. The current knowledge on the phosphorylation
status of plant oil body (OB) proteins is inadequate. This present study
identifies the distinct physiological substrates of Arabidopsis
serine/threonine/tyrosine protein kinase (STYK) and its role in seed oil
accumulation; the role of Arabidopsis OLE1, a major seed OB protein has also been
elucidated. In vitro kinase assay followed by mass spectrometry identifies
residue that are phosphorylated by STYK. Further, co-expression of OLE1 and STYK
in yeast cells increases the cellular lipid levels and reduces the total lipid
when OLE1 was replaced with OLE1T166A. Moreover, in vivo experiments with OB
isolated from wild-type and styk knock-out lines show the ability of STYK to
phosphorylate distinct OB proteins. OLE1T166A mutant and Arabidopsis styk mutant
demonstrate the significant reduction of its substrate phosphorylation. styk
mutant line significantly reduces the amount of total seed oil as compared to
wild-type seeds. Together, our results provide the evidences that Arabidopsis
At2G24360 (STYK) is phosphorylating oil body proteins and the phosphorylation
regulates the oil content in Arabidopsis seeds.
PMID- 29348627
TI - Chikungunya virus nsP1 interacts directly with nsP2 and modulates its ATPase
activity.
AB - Chikungunya virus (CHIKV) is a mosquito-borne virus, which has created an
alarming threat in the world due to unavailability of vaccine and antiviral
compounds. The CHIKV nsP2 contains ATPase, RTPase, helicase and protease
activities, whereas, nsP1 is a viral capping enzyme. In alphaviruses, the four
non-structural proteins form the replication complex in the cytoplasm and this
study characterizes the interaction between CHIKV nsP1 and nsP2. It was observed
that, both the proteins co-localize in the cytoplasm and interact in the CHIKV
infected cells by confocal microscopy and immunoprecipitation assay. Further, it
was demonstrated through mutational analysis that, the amino acids 1-95 of nsP2
and 170-288 of nsP1 are responsible for their direct interaction. Additionally,
it was noticed that, the ATPase activity of nsP2 is enhanced in the presence of
nsP1, indicating the functional significance of this interaction. In silico
analysis showed close (<=1.7 A) polar interaction (hydrogen bond) between Glu4,
Arg7, 96, 225 of nsP2 with Lys256, 206, Val367 and Phe312 of nsP1 respectively.
Hence, this investigation provides molecular characterization of CHIKV nsP1-nsP2
interaction which might be a useful target for rational designing of antiviral
drugs.
PMID- 29348628
TI - FEZF1-AS1/miR-107/ZNF312B axis facilitates progression and Warburg effect in
pancreatic ductal adenocarcinoma.
AB - Long non-coding RNAs (lncRNAs) play a pivotal role in pathological processes.
However, little information has been published regarding the underlying functions
and mechanisms of lncRNAs in pancreatic ductal adenocarcinoma (PDAC). A novel
lncRNA FEZF1-AS1 and its sense-cognate gene ZNF312B were found to be highly
expressed in human PDAC tissues and cell lines, which is associated with disease
progression and predicts clinical outcome in PDAC patients. Of note,
bioinformatics analysis, luciferase assays and RNA immunoprecipitation assays
indicated that FEZF1-AS1 may act as an endogenous sponge by competing for miR
107, thereby modulating the derepression of ZNF312B. Downregulation of FEZF1-AS1
or ZNF312B significantly inhibited proliferation, colony formation, migration,
and invasion of PDAC cells in vitro, whereas the miR-107 inhibitor abrogated the
effect of dow-regulation of FEZF1-AS1 or ZNF312B in reducing oncogenic capacities
of PDAC cells. In addition, FEZF1-AS1/miR-107/ZNF312B axis-induced promotion of
PDAC cells proliferation appeared to be mediated by modulation of the apoptosis
and the G1-S checkpoint. Furthermore, downregulation of FEZF1-AS1 repressed tumor
growth in mouse xenograft models. In particular, our results highlight the
contribution of FEZF1-AS1/miR-107/ZNF312B axis to Warburg effect maintenance of
PDAC cells. Collectively, our findings demonstrate that the FEZF1-AS1/miR
107/ZNF312B axis regulatory network might provide a potential new therapeutic
strategy for PDAC.
PMID- 29348629
TI - The suppressive role of calcium sensing receptor in endometrial cancer.
AB - Studies have shown that calcium sensing receptor (CaSR) is involved in the
progressions of several human cancers. However, the role of CaSR in endometrial
cancer remains unknown. This study provides a preliminary analysis of the CaSR
effect on endometrial cancer development. Ectopic CaSR expression by lentiviral
transfection (CaSR-OV) in Ishikawa cells significantly increased intracellular
calcium ([Ca2+]i) levels and cell apoptosis. E-cadherin and beta-catenin
expression and complex formation at the membrane were increased in CaSR-OV
Ishikawa cells relative to control Ishikawa cells (vector). Furthermore, CaSR-OV
Ishikawa cells showed a reduced invasive potential, which was attributed to E
cadherin/beta-catenin complex formation. Moreover, a reduction in CaSR expression
in endometrial cancer relative to normal specimens was evident by
immunohistochemistry and was positively associated with E-cadherin, but not beta
catenin, expression. Furthermore, VEGFR3 was significantly down-regulated in CaSR
OV Ishikawa cells. Additionally, an immunohistochemical analysis showed that
VEGFR3 was significantly increased in endometrial cancer compared with the normal
endometrium and was inversely correlated with CaSR expression. However, the CaSR
knockdown produced the opposite effects. These findings suggest an inhibitory
role for CaSR in endometrial cancer. Therefore, reduced CaSR expression may be a
suitable explanation and valuable predictor for endometrial cancer progression.
PMID- 29348630
TI - Expression of inflammasome proteins and inflammasome activation occurs in human,
but not in murine keratinocytes.
AB - Inflammasomes are multimeric protein complexes that assemble upon sensing of a
variety of stress factors. Their formation results in caspase-1-mediated
activation and secretion of the pro-inflammatory cytokines pro-interleukin(IL)
1beta and -18, which induce an inflammatory response. Inflammation is supported
by a lytic form of cell death, termed pyroptosis. Innate immune cells, such as
macrophages or dendritic cells, express and activate inflammasomes. However, it
has also been demonstrated that human primary keratinocytes activate different
types of inflammasomes in vitro, for example, upon UVB irradiation or viral
infection. Keratinocytes are the main cell type of the epidermis, the outermost
layer of the body, and form a protective barrier consisting of a stratified multi
layered epithelium. In human, gain-of-function mutations of the NLRP1 gene cause
syndromes mediated by inflammasome activation in keratinocytes that are
characterised by skin inflammation and skin cancer susceptibility. Here we
demonstrate that murine keratinocytes do not activate inflammasomes in response
to stimuli, which induce IL-1beta and -18 secretion by human keratinocytes.
Whereas murine keratinocytes produced caspase-1 and proIL-18, expression of the
inflammasome proteins Nlrp1, Nlrp3, Aim2, Asc, and proIL-1beta was, compared to
human keratinocytes or murine dendritic cells, very low or even undetectable.
Priming of murine keratinocytes with cytokines commonly used for induction of
proIL-1beta and inflammasome protein expression did not rescue inflammasome
activation. Nevertheless, UVB-induced inflammation and neutrophil recruitment in
murine skin was dependent on IL-1beta and caspase-1. However, also under these
conditions, we did not detect expression of proIL-1beta by keratinocytes in
murine skin, but by immune cells. These results demonstrate a higher
immunological competence of human compared to murine keratinocytes, which is
reflected by stress-induced IL-1beta secretion that is mediated by inflammasomes.
Therefore, keratinocytes in human skin can exert immune functions, which are
carried out by professional immune cells in murine skin.
PMID- 29348631
TI - Dynamic all-optical drug screening on cardiac voltage-gated ion channels.
AB - Voltage-gated ion channels (VGCs) are prime targets for the pharmaceutical
industry, but drug profiling on VGCs is challenging, since drug interactions are
confined to specific conformational channel states mediated by changes in
transmembrane potential. Here we combined various optogenetic tools to develop
dynamic, high-throughput drug profiling assays with defined light-step protocols
to interrogate VGC states on a millisecond timescale. We show that such light
induced electrophysiology (LiEp) yields high-quality pharmacological data with
exceptional screening windows for drugs acting on the major cardiac VGCs,
including hNav1.5, hKv1.5 and hERG. LiEp-based screening remained robust when
using a variety of optogenetic actuators (ChR2, ChR2(H134R), CatCh, ChR2-EYFP
betaArchT) and different types of organic (RH421, Di-4-ANBDQPQ, BeRST1) or
genetic voltage sensors (QuasAr1). The tractability of LiEp allows a versatile
and precise alternative to state-of-the-art VGC drug screening platforms such as
automated electrophysiology or FLIPR readers.
PMID- 29348632
TI - Climate Degradation and Extreme Icing Events Constrain Life in Cold-Adapted
Mammals.
AB - Despite the growth in knowledge about the effects of a warming Arctic on its cold
adapted species, the mechanisms by which these changes affect animal populations
remain poorly understood. Increasing temperatures, declining sea ice and altered
wind and precipitation patterns all may affect the fitness and abundance of
species through multiple direct and indirect pathways. Here we demonstrate
previously unknown effects of rain-on-snow (ROS) events, winter precipitation,
and ice tidal surges on the Arctic's largest land mammal. Using novel field data
across seven years and three Alaskan and Russian sites, we show arrested skeletal
growth in juvenile muskoxen resulting from unusually dry winter conditions and
gestational ROS events, with the inhibitory effects on growth from ROS events
lasting up to three years post-partum. Further, we describe the simultaneous
entombment of 52 muskoxen in ice during a Chukchi Sea winter tsunami (ivuniq in
Inupiat), and link rapid freezing to entrapment of Arctic whales and otters. Our
results illustrate how once unusual, but increasingly frequent Arctic weather
events affect some cold-adapted mammals, and suggest that an understanding of
species responses to a changing Arctic can be enhanced by coalescing groundwork,
rare events, and insights from local people.
PMID- 29348633
TI - Contrasting patterns of prehistoric human diet and subsistence in northernmost
Europe.
AB - Current archaeological evidence indicates the transition from hunting-fishing
gathering to agriculture in Northern Europe was a gradual process. This
transition was especially complex in the prehistoric North Fennoscandian
landscape where the high latitude posed a challenge to both domestic animal
breeding and cereal cultivation. The conditions varied, the coastal dwellers had
access to rich marine resources and enjoyed a milder climate due to the Gulf
Stream, while those living in the inland Boreal forest zone faced longer and
colder winters and less diversity in animal and plant resources. Thus, the
coastal area provided more favourable conditions for early agriculture compared
to those found inland. Interestingly, a cultural differentiation between these
areas is archaeologically visible from the late 2nd millennium BC onwards. This
is most clearly seen in regionally distinct pottery styles, offering unique
opportunities to probe diet and subsistence through the organic residues
preserved in ceramic vessels. Herein, we integrate the lipid biomarker, compound
specific stable carbon isotopes (delta13C), and zooarchaeological evidence to
reveal culturally distinct human diets and subsistence patterns. In northern
Norway, some of the coastal people adopted dairying as part of their subsistence
strategy, while the inhabitants of the interior, in common with northern Finland,
continued their hunter-gatherer-fisher lifestyles.
PMID- 29348635
TI - Publisher Correction: Spermine synthase deficiency causes lysosomal dysfunction
and oxidative stress in models of Snyder-Robinson syndrome.
AB - The originally published version of this Article contained errors in Figure 1. In
panel c, the grey shading denoting evolutionary conservation and the arrowheads
indicating amino acids affected in Snyder-Robinson syndrome were displaced
relative to the sequence. These errors have now been corrected in both the PDF
and HTML versions of the manuscript.
PMID- 29348634
TI - A biosensor-based framework to measure latent proteostasis capacity.
AB - The pool of quality control proteins (QC) that maintains protein-folding
homeostasis (proteostasis) is dynamic but can become depleted in human disease. A
challenge has been in quantitatively defining the depth of the QC pool. With a
new biosensor, flow cytometry-based methods and mathematical modeling we measure
the QC capacity to act as holdases and suppress biosensor aggregation. The
biosensor system comprises a series of barnase kernels with differing folding
stability that engage primarily with HSP70 and HSP90 family proteins. Conditions
of proteostasis stimulation and stress alter QC holdase activity and aggregation
rates. The method reveals the HSP70 chaperone cycle to be rate limited by HSP70
holdase activity under normal conditions, but this is overcome by increasing
levels of the BAG1 nucleotide exchange factor to HSPA1A or activation of the heat
shock gene cluster by HSF1 overexpression. This scheme opens new paths for
biosensors of disease and proteostasis systems.
PMID- 29348636
TI - The gamma gap predicts 4-year all-cause mortality among nonagenarians and
centenarians.
AB - Recent studies have revealed the prognostic role of the gamma gap, the total
serum proteins concentration minus the albumin concentration, for predicting all
cause mortality among adults. This study aims to investigate the relationship
between the gamma gap and all-cause mortality among nonagenarians and
centenarians via a secondary data analysis of a prospective observational study.
The analysis included 801 participants (260 men and 541 women, mean age: 93.7 +/-
3.5 years), 46 of which were lost at the 4-year follow-up. The mean gamma gap was
2.7 +/- 0.5 g/dl. After adjusting for relevant confounders, the gamma gap was
significantly associated with 4-year all-cause mortality (hazard ratio [HR] per 1
SD = 1.22, 95% confidential interval [CI]: 1.12-1.78). Using different cut-off
points, the elevated gamma gap could be defined as >=2.9, 3.0, 3.1, or 3.2 g/dl.
The relevant HRs and 95% CIs of the elevated gamma gap for predicting mortality
were 1.27 (1.12-1.90), 1.29 (1.03-1.78), 1.21 (1.23-1.66), and 1.26 (1.09-1.69),
respectively. In conclusion, the gamma gap is an independent prognostic factor
for long-term mortality in nonagenarians and centenarians. A value greater than
or equal to 3.1 g/dl may define an elevated gamma gap, but further studies are
required.
PMID- 29348637
TI - Plasmodium dihydrofolate reductase is a second enzyme target for the antimalarial
action of triclosan.
AB - Malaria, caused by parasites of the genus Plasmodium, leads to over half a
million deaths per year, 90% of which are caused by Plasmodium falciparum. P.
vivax usually causes milder forms of malaria; however, P. vivax can remain
dormant in the livers of infected patients for weeks or years before re-emerging
in a new bout of the disease. The only drugs available that target all stages of
the parasite can lead to severe side effects in patients with glucose-6-phosphate
dehydrogenase (G6PD) deficiency; hence, there is an urgent need to develop new
drugs active against blood and liver stages of the parasite. Different groups
have demonstrated that triclosan, a common antibacterial agent, targets the
Plasmodium liver enzyme enoyl reductase. Here, we provide 4 independent lines of
evidence demonstrating that triclosan specifically targets both wild-type and
pyrimethamine-resistant P. falciparum and P. vivax dihydrofolate reductases,
classic targets for the blood stage of the parasite. This makes triclosan an
exciting candidate for further development as a dual specificity antimalarial,
which could target both liver and blood stages of the parasite.
PMID- 29348639
TI - Evidence of local structural influence on the shape driven magnetic anisotropy in
electronically excited Ni nanoparticles embedded in SiO2 matrix.
AB - The reliance of modern electronic era on ultrafast data recording has made the
search for novel tools to tune nano-scale magnetic-anisotropy (MA) never-ending.
We demonstrate a strong correlation between the spin-spin interactions, local
atomic structure and the MA of Ni nanoparticles (NPs) embedded inside SiO2 matrix
under swift heavy ion (SHI) irradiation. In contrast to traditional
understandings, MA in Ni NPs along with their aspect ratio, first increases upto
5 * 1013 ions/cm2 SHI fluence (5e13) and gets reduced at highest fluence. Using
angle dependent Extented-Xray-Absorption-Fine-Structure (EXAFS) and ab initio
molecular dynamics (MD) simulations, we show that the anisotropy induced in local
atomic structure upon irradiation is dependent on atomic spin-spin interactions,
which gets reduced at highest fluence. The chosen model cluster (Ni38) used in
our MD simulations is duly validated by comparing the pair-correlation-function
of the structure with the EXAFS-Fourier-Transform. The lattice temperatures for
the films irradiated at different fluences, as calculated from thermal-spike
model, are used for the respective MD runs. We conclude that the enhanced
disorder in both the local atomic environment and spin alignment destroys the MA
at the highest fluence in SHI irradiated Ni NPs. The findings therefore provide
rich conceptual insights for designing magnetic devices using SHI-induced
phenomena.
PMID- 29348640
TI - Predators on top.
PMID- 29348638
TI - Changes in cytokine responses to TB antigens ESAT-6, CFP-10 and TB 7.7 and
inflammatory markers in peripheral blood during therapy.
AB - Multiple cytokines and inflammatory markers control TB infection. We aimed to
investigate the changes in multiple cytokines and inflammatory markers in active
TB patients following anti-TB drug therapy. Twenty-nine patients with active TB
were recruited prospectively between December 2010 and July 2017. Blood samples
were collected before (T0), after 2 months (T2), and at the end of anti-TB
treatment (Tend). We measured the levels of Interferon (IFN)-gamma, interleukin
(IL)-2, IL-12, IL-10, IL-13 and tumor necrosis factor (TNF)-alpha in supernatants
collected from the QuantiFERON-TB Gold In-Tube assay (QFT-GIT), as well as the
WBC, neutrophil, platelet count and neutrophil to lymphocyte ratio (NLR) in whole
blood. Compared with baseline levels, WBC, neutrophil, and platelet counts were
significantly lower following treatment. In addition, the NLR after treatment
significantly decreased compared with baseline, whereas the IL-2/IFN-gamma ratio
increased after treatment. In conclusion, the levels of IL-2/IFN-gamma ratios in
the supernatant and the NLR might be useful biomarkers to evaluate the
effectiveness of drug therapy in active TB patients.
PMID- 29348641
TI - Refined control of cell stemness allowed animal evolution in the oxic realm.
AB - Animal diversification on Earth has long been presumed to be associated with the
increasing extent of oxic niches. Here, we challenge that view. We start with the
fact that hypoxia (<1-3% O2) maintains cellular immaturity (stemness), whereas
adult stem cells continuously-and paradoxically-regenerate animal tissue in
oxygenated settings. Novel insights from tumour biology illuminate how cell
stemness nevertheless can be achieved through the action of oxygen-sensing
transcription factors in oxygenated, regenerating tissue. We suggest that these
hypoxia-inducible transcription factors provided animals with unprecedented
control over cell stemness that allowed them to cope with fluctuating oxygen
concentrations. Thus, a refinement of the cellular hypoxia-response machinery
enabled cell stemness at oxic conditions and, then, animals to evolve into the
oxic realm. This view on the onset of animal diversification is consistent with
geological evidence and provides a new perspective on the challenges and
evolution of multicellular life.
PMID- 29348642
TI - The success of failed Homo sapiens dispersals out of Africa and into Asia.
AB - The evidence for an early dispersal of Homo sapiens from Africa into the Levant
during Marine Isotope Stage 5 (MIS-5) 126-74 ka (thousand years ago) was
characterized for many years as an 'abortive' expansion: a precursor to a
sustained dispersal from which all extant human populations can be traced. Recent
archaeological and genetic data from both western and eastern parts of Eurasia
and from Australia are starting to challenge that interpretation. This
Perspective reviews the current evidence for a scenario where the MIS-5 dispersal
encompassed a much greater geographic distribution and temporal duration. The
implications of this for tracking and understanding early human dispersal in
Southeast Asia specifically are considered, and the validity of measuring
dispersal success only through genetic continuity into the present is examined.
PMID- 29348643
TI - A trillion trees.
PMID- 29348644
TI - Global priorities for conserving the evolutionary history of sharks, rays and
chimaeras.
AB - In an era of accelerated biodiversity loss and limited conservation resources,
systematic prioritization of species and places is essential. In terrestrial
vertebrates, evolutionary distinctness has been used to identify species and
locations that embody the greatest share of evolutionary history. We estimate
evolutionary distinctness for a large marine vertebrate radiation on a dated
taxon-complete tree for all 1,192 chondrichthyan fishes (sharks, rays and
chimaeras) by augmenting a new 610-species molecular phylogeny using taxonomic
constraints. Chondrichthyans are by far the most evolutionarily distinct of all
major radiations of jawed vertebrates-the average species embodies 26 million
years of unique evolutionary history. With this metric, we identify 21 countries
with the highest richness, endemism and evolutionary distinctness of threatened
species as targets for conservation prioritization. On average, threatened
chondrichthyans are more evolutionarily distinct-further motivating improved
conservation, fisheries management and trade regulation to avoid significant
pruning of the chondrichthyan tree of life.
PMID- 29348646
TI - Intergenerational equity can help to prevent climate change and extinction.
PMID- 29348645
TI - A global perspective on the trophic geography of sharks.
AB - Sharks are a diverse group of mobile predators that forage across varied spatial
scales and have the potential to influence food web dynamics. The ecological
consequences of recent declines in shark biomass may extend across broader
geographic ranges if shark taxa display common behavioural traits. By tracking
the original site of photosynthetic fixation of carbon atoms that were ultimately
assimilated into muscle tissues of 5,394 sharks from 114 species, we identify
globally consistent biogeographic traits in trophic interactions between sharks
found in different habitats. We show that populations of shelf-dwelling sharks
derive a substantial proportion of their carbon from regional pelagic sources,
but contain individuals that forage within additional isotopically diverse local
food webs, such as those supported by terrestrial plant sources, benthic
production and macrophytes. In contrast, oceanic sharks seem to use carbon
derived from between 30 degrees and 50 degrees of latitude. Global-scale
compilations of stable isotope data combined with biogeochemical modelling
generate hypotheses regarding animal behaviours that can be tested with other
methodological approaches.
PMID- 29348647
TI - The contribution of predators and scavengers to human well-being.
AB - Predators and scavengers are frequently persecuted for their negative effects on
property, livestock and human life. Research has shown that these species play
important regulatory roles in intact ecosystems including regulating herbivore
and mesopredator populations that in turn affect floral, soil and hydrological
systems. Yet predators and scavengers receive surprisingly little recognition for
their benefits to humans in the landscapes they share. We review these benefits,
highlighting the most recent studies that have documented their positive effects
across a range of environments. Indeed, the benefits of predators and scavengers
can be far reaching, affecting human health and well-being through disease
mitigation, agricultural production and waste-disposal services. As many
predators and scavengers are in a state of rapid decline, we argue that
researchers must work in concert with the media, managers and policymakers to
highlight benefits of these species and the need to ensure their long-term
conservation. Furthermore, instead of assessing the costs of predators and
scavengers only in economic terms, it is critical to recognize their beneficial
contributions to human health and well-being. Given the ever-expanding human
footprint, it is essential that we construct conservation solutions that allow a
wide variety of species to persist in shared landscapes. Identifying, evaluating
and communicating the benefits provided by species that are often considered
problem animals is an important step for establishing tolerance in these shared
spaces.
PMID- 29348649
TI - Publisher Correction: Determination of total and unbound docetaxel in plasma by
ultrafiltration and UPLC-MS/MS: application to pharmacokinetic studies.
AB - A correction to this article has been published and is linked from the HTML
version of this paper. The error has been fixed in the paper.
PMID- 29348648
TI - Specific cyclic ADP-ribose phosphohydrolase obtained by mutagenic engineering of
Mn2+-dependent ADP-ribose/CDP-alcohol diphosphatase.
AB - Cyclic ADP-ribose (cADPR) is a messenger for Ca2+ mobilization. Its turnover is
believed to occur by glycohydrolysis to ADP-ribose. However, ADP-ribose/CDP
alcohol diphosphatase (ADPRibase-Mn) acts as cADPR phosphohydrolase with much
lower efficiency than on its major substrates. Recently, we showed that
mutagenesis of human ADPRibase-Mn at Phe37, Leu196 and Cys253 alters its
specificity: the best substrate of the mutant F37A + L196F + C253A is cADPR by a
short difference, Cys253 mutation being essential for cADPR preference. Its
proximity to the 'northern' ribose of cADPR in docking models indicates Cys253 is
a steric constraint for cADPR positioning. Aiming to obtain a specific cADPR
phosphohydrolase, new mutations were tested at Asp250, Val252, Cys253 and Thr279,
all near the 'northern' ribose. First, the mutant F37A + L196F + C253G, with a
smaller residue 253 (Ala > Gly), showed increased cADPR specificity. Then, the
mutant F37A + L196F + V252A + C253G, with another residue made smaller (Val >
Ala), displayed the desired specificity, with cADPR kcat/KM ~20-200-fold larger
than for any other substrate. When tested in nucleotide mixtures, cADPR was
exhausted while others remained unaltered. We suggest that the specific cADPR
phosphohydrolase, by cell or organism transgenesis, or the designed mutations, by
genome editing, provide opportunities to study the effect of cADPR depletion on
the many systems where it intervenes.
PMID- 29348650
TI - Glacial vicariance drives phylogeographic diversification in the amphi-boreal
kelp Saccharina latissima.
AB - Glacial vicariance is regarded as one of the most prevalent drivers of
phylogeographic structure and speciation among high-latitude organisms, but
direct links between ice advances and range fragmentation have been more
difficult to establish in marine than in terrestrial systems. Here we investigate
the evolution of largely disjunct (and potentially reproductively isolated)
phylogeographic lineages within the amphi-boreal kelp Saccharina latissima s. l.
Using molecular data (COI, microsatellites) we confirm that S. latissima
comprises also the NE Pacific S. cichorioides complex and is composed of
divergent lineages with limited range overlap and genetic admixture. Only a few
genetic hybrids were detected throughout a Canadian Arctic/NW Greenland contact
zone. The degree of genetic differentiation and sympatric isolation of
phylogroups suggest that S. latissima s. l. represents a complex of incipient
species. Phylogroup distributions compared with paleo-environmental
reconstructions of the cryosphere further suggest that diversification within S.
latissima results from chronic glacial isolation in disjunct persistence areas
intercalated with ephemeral interglacial poleward expansions and admixture at
high-latitude (Arctic) contact zones. This study thus supports a role for
glaciations not just in redistributing pre-existing marine lineages but also as a
speciation pump across multi-glacial cycles for marine organisms otherwise
exhibiting cosmopolite amphi-boreal distributions.
PMID- 29348652
TI - Intensification of ice nucleation observed in ocean ship emissions.
AB - Shipping contributes primary and secondary emission products to the atmospheric
aerosol burden that have implications for climate, clouds, and air quality from
regional to global scales. In this study we exam the potential impact of ship
emissions with regards to ice nucleating particles. Particles that nucleate ice
are known to directly affect precipitation and cloud microphysical properties. We
have collected and analyzed particles for their ice nucleating capacity from a
shipping channel outside a large Scandinavia port. We observe that ship plumes
amplify the background levels of ice nucleating particles and discuss the larger
scale implications. The measured ice nucleating particles suggest that the
observed amplification is most likely important in regions with low levels of
background particles. The Arctic, which as the sea ice pack declines is opening
to transit and natural resource exploration and exploitation at an ever
increasing rate, is highlighted as such a region.
PMID- 29348651
TI - Depressive mood ratings are reduced by MDMA in female polydrug ecstasy users
homozygous for the l-allele of the serotonin transporter.
AB - MDMA exerts its main effects via the serotonergic system and the serotonin
transporter. The gene coding for this transporter determines the expression rate
of the transporter. Previously it was shown that healthy individuals with the
short allelic variant ('s-group') of the 5-HTTLPR-polymorphism displayed more
anxiety and negative mood, and had a lower transcriptional efficiency compared to
individuals who are homozygous for the l-allele ('l-group'). The present study
aimed to investigate the role of the 5-HTTLPR polymorphism in MDMA-induced mood
effects. Four placebo-controlled, within-subject studies were pooled, including
in total 63 polydrug ecstasy users (Ns-group = 48; Nl-group = 15) receiving MDMA
75 mg and placebo on two test days, separated by minimally 7 days. Mood was
assessed by means of the Profile of Mood States. Findings showed that MDMA
induced -independent of sex- a positive mood state, and as a side effect also
increased two negative affect states, anxiety and confusion. Anxiety ratings were
higher in the l-group and independent of treatment or sex. Depression ratings
were lowered by MDMA in the female l-group. Findings indicate that the MDMA
induced reduction in self-rated depressive feelings is sex- and genotype
dependent, with females homozygous for the l-allele showing this beneficial
effect.
PMID- 29348653
TI - Non-structural carbohydrates regulated by season and species in the subtropical
monsoon broad-leaved evergreen forest of Yunnan Province, China.
AB - Non-structural carbohydrates (NSC) play important roles in adapting to
environments in plants. Despite extensive research on the seasonal dynamics and
species differences of NSC, the relative contributions of season and species to
NSC is not well understood. We measured the concentration of starch, soluble
sugar, NSC, and the soluble sugar:starch ratio in leaves, twigs, trunks and roots
of twenty dominant species for dry and wet season in monsoon broad-leaved
evergreen forest, respectively. The majority of concentration of NSC and starch
in the roots, and the leaves contained the highest concentration of soluble
sugar. A seasonal variation in starch and NSC concentrations higher in the dry
season. Conversely, the wet season samples had higher concentration of soluble
sugar and the sugar:starch ratio. Significant differences exist for starch,
soluble sugar and NSC concentrations and the sugar:starch ratio across species.
Most species had higher starch and NSC concentrations in the dry season and
higher soluble sugar concentration and the sugar:starch ratio in wet season.
Repeated variance analysis showed that starch and NSC concentrations were
strongly affected by season although the effect of seasons, species, and the
interaction of the two on the starch, soluble sugar, and NSC concentrations were
significant.
PMID- 29348655
TI - The headache of temporomandibular disorders.
AB - This article endeavours to revise the key guidance and evidence on
temporomandibular disorders (TMD), with a particular focus on myofascial pain. It
highlights the important role that primary care dental practitioners play in
providing holistic care during the patient's journey to manage this painful
condition. I hope to give an insight into my own personal experiences to
highlight the challenges patients can face in seeking appropriate support.
PMID- 29348654
TI - Low concentration trifluoperazine promotes proliferation and reduces calcium
dependent apoptosis in glioma cells.
AB - Glioma patients constitute the greatest percentage of depressed neoplasm
patients. These patients often require antidepressant treatment, but the effect
of antidepressant drugs on glioma cells requires further evaluation. In the
present study, we evaluated the effect of trifluoperazine (TFP) on the
proliferation and apoptosis of glioma cells. Transcriptomic and bioinformatics
analysis results suggested that antidepressant drugs, especially TFP, may
upregulate the drug-resistant ability of glioma cells. A low concentration of TFP
upregulated the viability of glioma cells. Colony formation and EdU assays
confirmed that TFP treatment accelerates glioma cell proliferation, but no
significant difference was found in the cell cycle distribution of glioma cells
after treatment with TFP or control. Flow cytometry and TUNEL staining results
suggested that TFP treatment decreased apoptosis in glioma cells. In addition,
TFP treatment downregulated the intracellular Ca2+ concentration of glioma cells.
In vivo experimental results indicated that TFP treatment promoted proliferation
and reduced apoptosis in xenograft tumours in nude mice. Taken together, our
results suggest that a low concentration of TFP promotes proliferation and
reduces apoptosis in glioma cells both in vitro and in vivo. The potential
harmful effects of antidepressant drugs on gliomas require further evaluation
before their use in glioma patients.
PMID- 29348656
TI - Quantifying the Risk and Cost of Active Monitoring for Infectious Diseases.
AB - During outbreaks of deadly emerging pathogens (e.g., Ebola, MERS-CoV) and
bioterror threats (e.g., smallpox), actively monitoring potentially infected
individuals aims to limit disease transmission and morbidity. Guidance issued by
CDC on active monitoring was a cornerstone of its response to the West Africa
Ebola outbreak. There are limited data on how to balance the costs and
performance of this important public health activity. We present a framework that
estimates the risks and costs of specific durations of active monitoring for
pathogens of significant public health concern. We analyze data from New York
City's Ebola active monitoring program over a 16-month period in 2014-2016. For
monitored individuals, we identified unique durations of active monitoring that
minimize expected costs for those at "low (but not zero) risk" and "some or high
risk": 21 and 31 days, respectively. Extending our analysis to smallpox and MERS
CoV, we found that the optimal length of active monitoring relative to the median
incubation period was reduced compared to Ebola due to less variable incubation
periods. Active monitoring can save lives but is expensive. Resources can be most
effectively allocated by using exposure-risk categories to modify the duration or
intensity of active monitoring.
PMID- 29348657
TI - An ethylene response factor (MxERF4) functions as a repressor of Fe acquisition
in Malus xiaojinensis.
AB - Iron (Fe) is an essential element for plants; however, its availability is
limited as it forms insoluble complexes in the soil. Consequently, plants have
developed mechanisms to adapt to low Fe conditions. We demonstrate that ethylene
is involved in Fe deficiency-induced physiological responses in Malus
xiaojinensis, and describe the identification of MxERF4 as a protein-protein
interaction partner with the MxFIT transcription factor, which is involved in the
iron deficiency response. Furthermore, we demonstrate that MxERF4 acts as an
MxFIT interaction partner to suppresses the expression of the Fe transporter
MxIRT1, by binding directly to its promoter, requiring the EAR motif of the
MxERF4 protein. Suppression of MxERF4 expression in M. xiaojinensis, using virus
induced gene silencing resulted in an increase in MxIRT1 expression. Taken
together, the results suggest a repression mechanism, where ethylene initiates
the Fe deficiency response, and the response is then dampened, which may require
a transient inhibition of Fe acquisition via the action of MxERF4.
PMID- 29348658
TI - Novel multifunctional cheese-like 3D carbon-BN as a highly efficient adsorbent
for water purification.
AB - In this paper, a novel three dimensional carbon boron nitride (3D C-BN) was
successfully prepared. The obtained material has porous cheese-like structure and
pore size ranging from 2 nm to 100 nm. Attractively, the 3D C-BN, which combines
the adsorption advantages of BN and carbon together, exhibits excellent
adsorption properties for organic dyes, oils and heavy metal ions. The maximum
removal capacities of 3D C-BN for methyl blue (MB) and congo red (CR) are 408 mg
g-1 and 307 mg g-1, respectively. Furthermore, 3D C-BN can quickly and
efficiently remove oils (salad oil, gasoline and pump oil) and heavy metal ions
(Cr3+, Cd2+ and Ni2+) from waste water. The macro bulk 3D C-BN, which is more
convenient to use than powdered materials, can be reused by burning or heating in
air and still maintains high adsorption capacity. Significantly, these superior
performances can find practical application in water purification.
PMID- 29348659
TI - BLM helicase suppresses recombination at G-quadruplex motifs in transcribed
genes.
AB - Bloom syndrome is a cancer predisposition disorder caused by mutations in the BLM
helicase gene. Cells from persons with Bloom syndrome exhibit striking genomic
instability characterized by excessive sister chromatid exchange events (SCEs).
We applied single-cell DNA template strand sequencing (Strand-seq) to map the
genomic locations of SCEs. Our results show that in the absence of BLM, SCEs in
human and murine cells do not occur randomly throughout the genome but are
strikingly enriched at coding regions, specifically at sites of guanine
quadruplex (G4) motifs in transcribed genes. We propose that BLM protects against
genome instability by suppressing recombination at sites of G4 structures,
particularly in transcribed regions of the genome.
PMID- 29348660
TI - Generation and Characterization of Alloantigen-Specific Regulatory T Cells For
Clinical Transplant Tolerance.
AB - Donor-specific CD4+CD127-CD25+FOXP3+ regulatory T cells (AgTregs) have the
potential to induce clinical transplant tolerance; however, their expansion ex
vivo remains challenging. We optimized a novel expansion protocol to stimulate
donor-specific Tregs using soluble 4-trimer CD40 ligand (CD40L)-activated donor B
cells that expressed mature antigen-presenting cell markers. This avoided the use
of CD40L-expressing stimulator cells that might otherwise result in potential
cellular contamination. Purified allogeneic "recipient" CD4+CD25+ Tregs were
stimulated on days 0 and 7 with expanded "donor" B cells in the presence of IL-2,
TGFbeta and sirolimus (SRL). Tregs were further amplified by polyclonal
stimulation with anti-CD3/CD28 beads on day 14 without SRL, and harvested on day
21, with extrapolated fold expansion into the thousands. The expanded AgTregs
maintained expression of classical Treg markers including demethylation of the
Treg-specific demethylated region (CNS2) and also displayed constricted TcR
repertoire. We observed AgTregs more potently inhibited MLR than polyclonally
expanded Tregs and generated new Tregs in autologous responder cells (a measure
of infectious tolerance). Thus, an optimized and more clinically applicable
protocol for the expansion of donor-specific Tregs has been developed.
PMID- 29348661
TI - Highly efficient and stable inverted perovskite solar cell employing PEDOT:GO
composite layer as a hole transport layer.
AB - The beneficial use of a hole transport layer (HTL) as a substitution for poly(3,4
ethlyenedioxythiophene): polystyrene sulfonate (PEDOT:PSS) is regarded as one of
the most important approaches for improving the stability and efficiency of
inverted perovskite solar cells. Here, we demonstrate highly efficient and stable
inverted perovskite solar cells by applying a GO-doped PEDOT:PSS (PEDOT:GO) film
as an HTL. The high performance of this solar cell stems from the excellent
optical and electrical properties of the PEDOT:GO film, including a higher
electrical conductivity, a higher work function related to the reduced contact
barrier between the perovskite layer and the PEDOT:GO layer, enhanced
crystallinity of the perovskite crystal, and suppressed leakage current.
Moreover, the device with the PEDOT:GO layer showed excellent long-term stability
in ambient air conditions. Thus, the enhancement in the efficiency and the
excellent stability of inverted perovskite solar cells are promising for the
eventual commercialization of perovskite optoelectronic devices.
PMID- 29348662
TI - Endoscopic submucosal tunnel dissection using a novel bracing basket: An animal
feasibility study.
AB - The aim of this study was to evaluate the feasibility of a novel bracing basket
for Endoscopic submucosal tunnel dissection (ESTD), which was developed for
improved effectiveness and ease of use. This was a prospective randomized,
comparative, experimental animal study carried out at a single center. The
primary aim was to evaluate the efficacy of ESTD with a novel bracing basket,
compared with conventional ESTD. The secondary aims were to assess the quality
control of the procedures and adverse events. Twenty procedures (6 esophageal and
14 gastric) were performed in four pigs. All resections were completed as en bloc
resections. The technical success rate was 100% for both techniques (bracing
basket-assisted ESTD vs. conventional ESTD). The procedure times were similar,
but the cutting speed was quicker with bracing basket-assisted ESTD in gastric
(antrum:23.3 +/- 2.2 mm2/min vs. 15.2 +/- 3.2 mm2/min, body: 26.1 +/- 1.3 mm2/min
vs. 18.4 +/- 2.0 mm2/min, p < 0.05). There was one bleeding in the bracing basket
assisted ESTD group and one perforation in the conventional ESTD group. Compared
with conventional ESTD, the use of this basket has potential advantages.
Comparison studies with larger gastric or colorectal lesions treated with
conventional ESTD are needed.
PMID- 29348663
TI - Enhancer-associated long non-coding RNA LEENE regulates endothelial nitric oxide
synthase and endothelial function.
AB - The optimal expression of endothelial nitric oxide synthase (eNOS), the hallmark
of endothelial homeostasis, is vital to vascular function. Dynamically regulated
by various stimuli, eNOS expression is modulated at transcriptional, post
transcriptional, and post-translational levels. However, epigenetic modulations
of eNOS, particularly through long non-coding RNAs (lncRNAs) and chromatin
remodeling, remain to be explored. Here we identify an enhancer-associated lncRNA
that enhances eNOS expression (LEENE). Combining RNA-sequencing and chromatin
conformation capture methods, we demonstrate that LEENE is co-regulated with eNOS
and that its enhancer resides in proximity to eNOS promoter in endothelial cells
(ECs). Gain- and Loss-of-function of LEENE differentially regulate eNOS
expression and EC function. Mechanistically, LEENE facilitates the recruitment of
RNA Pol II to the eNOS promoter to enhance eNOS nascent RNA transcription. Our
findings unravel a new layer in eNOS regulation and provide novel insights into
cardiovascular regulation involving endothelial function.
PMID- 29348664
TI - Stress-induced TRBP phosphorylation enhances its interaction with PKR to regulate
cellular survival.
AB - Transactivation response element RNA-binding protein (TRBP or TARBP2) initially
identified to play an important role in human immunodeficiency virus (HIV)
replication also has emerged as a regulator of microRNA biogenesis. In addition,
TRBP functions in signaling pathways by negatively regulating the interferon
induced double-stranded RNA (dsRNA)-activated protein kinase (PKR) during viral
infections and cell stress. During cellular stress, PKR is activated and
phosphorylates the alpha subunit of the eukaryotic translation factor eIF2,
leading to the cessation of general protein synthesis. TRBP inhibits PKR activity
by direct interaction as well as by binding to PKR's two known activators, dsRNA
and PACT, thus preventing their interaction with PKR. In this study, we
demonstrate for the first time that TRBP is phosphorylated in response to
oxidative stress and upon phosphorylation, inhibits PKR more efficiently
promoting cell survival. These results establish that PKR regulation through
stress-induced TRBP phosphorylation is an important mechanism ensuring cellular
recovery and preventing apoptosis due to sustained PKR activation.
PMID- 29348665
TI - PCDHGA9 acts as a tumor suppressor to induce tumor cell apoptosis and autophagy
and inhibit the EMT process in human gastric cancer.
AB - The results of a cDNA array revealed that protocadherin gamma subfamily A, 9
(PCDHGA9) was significantly decreased in SGC-7901 gastric cancer (GC) cells
compared with GES-1 normal gastric cells and was strongly associated with the
Wnt/beta-catenin and transforming growth factor-beta (TGF-beta)/Smad2/3 signaling
pathway. As a member of the cadherin family, PCDHGA9 functions in both cell-cell
adhesion and nuclear signaling. However, its role in tumorigenicity or metastasis
has not been reported. In the present study, we found that PCDHGA9 was decreased
in GC tissues compared with corresponding normal mucosae and its expression was
correlated with the GC TNM stage, the UICC stage, differentiation, relapse, and
metastasis (p < 0.01). Multivariate Cox analysis revealed that PCDHGA9 was an
independent prognostic indicator for overall survival (OS) and disease-free
survival (DFS) (p < 0.01). The effects of PCDHGA9 on GC tumor growth and
metastasis were examined both in vivo and in vitro. PCDHGA9 knockdown promoted GC
cell proliferation, migration, and invasion, whereas PCDHGA9 overexpression
inhibited GC tumor growth and metastasis but induced apoptosis, autophagy, and G1
cell cycle arrest. Furthermore, PCDHGA9 suppressed epithelial-mesenchymal
transition (EMT) induced by TGF-beta, decreased the phosphorylation of Smad2/3,
and inhibited the nuclear translocation of pSmad2/3. Our results suggest that
PCDHGA9 might interact with beta-catenin to prevent beta-catenin from
dissociating in the cytoplasm and translocating to the nucleus. Moreover, PCDHGA9
overexpression restrained cell proliferation and reduced the nuclear beta
catenin, an indicator of Wnt/beta-catenin pathway activation, suggesting that
PCDHGA9 negatively regulates Wnt signaling. Together, these data indicate that
PCDHGA9 acts as a tumor suppressor with anti-proliferative activity and anti
invasive ability, and the reduction of PCDHGA9 could serve as an independent
prognostic biomarker in GC.
PMID- 29348667
TI - Neuroimmunology: Brain police.
PMID- 29348668
TI - Neurodegenerative disease: A proteostatic boost.
PMID- 29348669
TI - Learning and memory: You only learn once.
PMID- 29348666
TI - Mitochondria at the neuronal presynapse in health and disease.
AB - Synapses enable neurons to communicate with each other and are therefore a
prerequisite for normal brain function. Presynaptically, this communication
requires energy and generates large fluctuations in calcium concentrations.
Mitochondria are optimized for supplying energy and buffering calcium, and they
are actively recruited to presynapses. However, not all presynapses contain
mitochondria; thus, how might synapses with and without mitochondria differ?
Mitochondria are also increasingly recognized to serve additional functions at
the presynapse. Here, we discuss the importance of presynaptic mitochondria in
maintaining neuronal homeostasis and how dysfunctional presynaptic mitochondria
might contribute to the development of disease.
PMID- 29348671
TI - Superconducting gap anisotropy sensitive to nematic domains in FeSe.
AB - The structure of the superconducting gap in unconventional superconductors holds
a key to understand the momentum-dependent pairing interactions. In
superconducting FeSe, there have been controversial results reporting nodal and
nodeless gap structures, raising a fundamental issue of pairing mechanisms of
iron-based superconductivity. Here, by utilizing polarization-dependent laser
excited angle-resolved photoemission spectroscopy, we report a detailed momentum
dependence of the gap in single- and multi-domain regions of orthorhombic FeSe
crystals. We confirm that the superconducting gap has a twofold in-plane
anisotropy, associated with the nematicity due to orbital ordering. In twinned
regions, we clearly find finite gap minima near the vertices of the major axis of
the elliptical zone-centered Fermi surface, indicating a nodeless state. In
contrast, the single-domain gap drops steeply to zero in a narrow angle range,
evidencing for nascent nodes. Such unusual node lifting in multi-domain regions
can be explained by the nematicity-induced time-reversal symmetry breaking near
the twin boundaries.
PMID- 29348670
TI - Intradermal delivery of STAT3 siRNA to treat melanoma via dissolving
microneedles.
AB - Hyperactivity of signal transducer and activity of transcription 3 (STAT3) plays
a crucial role in melanoma invasion and metastasis. Gene therapy applying siRNA
targeting STAT3 is a potential therapeutic strategy for melanoma. In this
article, we first fabricated safe and novel dissolving microneedles (MNs) for
topical application of STAT3 siRNA to enhance the skin penetration of siRNA and
used polyethylenimine (PEI, 25 kDa) as carrier to improve cellular uptake of
siRNA. The results showed that MNs can effectively penetrate skin and rapidly
dissolve in the skin. In vitro B16F10 cell experiments presented that STAT3 siRNA
PEI complex can enhance cellular uptake and transfection of siRNA,
correspondingly enhance gene silencing efficiency and inhibit tumor cells growth.
In vivo experiments indicated that topical application of STAT3 siRNA PEI complex
delivered by dissolving MNs into skin can effectively suppress the development of
melanoma through silencing STAT3 gene, and the inhibition effect is dose
dependent. STAT3 siRNA delivery via dissolving MNs is a promising approach for
skin melanoma treatment with targeting inhibition efficacy and minimal adverse
effects.
PMID- 29348672
TI - Soluble LRP1 is an independent biomarker of epicardial fat volume in patients
with type 1 diabetes mellitus.
AB - Epicardial adipose tissue (EAT) is a metabolically active tissue intimately
associated with metabolic syndrome and cardiovascular disease. Quantification of
EAT volume is an interesting clinical tool for the evaluation of cardiometabolic
disease. Nevertheless, current methodology presents serious disadvantages. The
soluble form of the receptor LRP1 (sLRP1) is a non-invasive biomarker of EAT in
general population. Here, we analysed the potential of circulating sLRP1 as
biomarker of EAT volume in patients with type 1 diabetes mellitus (T1DM). The
study included a well-characterized cohort of T1DM patients without clinical
cardiovascular disease (N = 73). EAT volume was assessed by a multidetector
computed tomography (MDCT). sLRP1 and panel of inflammatory and endocrine
mediators were measured using commercially available ELISA. EAT volume showed a
direct association with circulating sLRP1 (beta = 0.398, P = 0.001) in univariate
linear regression analysis. This association was higher than that observed for
other potential inflammatory and endocrine biomarkers. Using multivariate linear
regression analyses, we demonstrated that the association between EAT volume and
circulating sLRP1 was independent of potential confounding factors, including
age, sex, body mass index, CRP, HbA1c and LDL-C (P < 0.050 for all multivariate
linear regression models). In conclusion, sLRP1 is an independent biomarker of
EAT in T1DM patients.
PMID- 29348673
TI - Quantification of massively parallel sequencing libraries - a comparative study
of eight methods.
AB - Quantification of massively parallel sequencing libraries is important for
acquisition of monoclonal beads or clusters prior to clonal amplification and to
avoid large variations in library coverage when multiple samples are included in
one sequencing analysis. No gold standard for quantification of libraries exists.
We assessed eight methods of quantification of libraries by quantifying 54
amplicon, six capture, and six shotgun fragment libraries. Chemically synthesized
double-stranded DNA was also quantified. Light spectrophotometry, i.e. NanoDrop,
was found to give the highest concentration estimates followed by Qubit and
electrophoresis-based instruments (Bioanalyzer, TapeStation, GX Touch, and
Fragment Analyzer), while SYBR Green and TaqMan based qPCR assays gave the lowest
estimates. qPCR gave more accurate predictions of sequencing coverage than Qubit
and TapeStation did. Costs, time-consumption, workflow simplicity, and ability to
quantify multiple samples are discussed. Technical specifications, advantages,
and disadvantages of the various methods are pointed out.
PMID- 29348674
TI - Variation at position 350 in the Chikungunya virus 6K-E1 protein determines the
sensitivity of detection in a rapid E1-antigen test.
AB - Chikungunya virus (CHIKV), a mosquito-borne pathogen, consists of three
genotypes: East/Central/South African (ECSA), West African (WA), and Asian.
Although a current rapid immunochromatographic (IC) test detecting CHIKV E1
antigen showed high sensitivity to ECSA-genotype viruses, it showed poor
performance against the Asian-genotype virus that is spreading in the American
continents. To understand the basis for the low performance of this IC test
against Asian-genotype virus, we re-examined the anti-CHIKV monoclonal antibodies
(mAbs) used in the assay for their interaction with E1-antigen of the three CHIKV
genotypes. We found that the reactivity of one mAb for Asian-genotype virus was
lower than that for ECSA virus. Comparison of E1 amino acid sequences revealed
that the ECSA virus used to generate these mAbs possesses glutamic acid (E) at
position 350, in contrast to WA and Asian, which possess aspartic acid (D) at
this position. Site-directed mutagenesis confirmed that the mutation altered mAb
reactivity, since E-to-D substitution at position 350 in ECSA reduced recognition
by the mAb, while D-to-E substitution at this position in Asian and WA increased
affinity for the mAb. Taken together, these results indicate that residue 350 of
the CHIKV 6K-E1 is a key element affecting the performance of this IC assay.
PMID- 29348675
TI - STAC2 negatively regulates osteoclast formation by targeting the RANK signaling
complex.
AB - The receptor activator of nuclear factor-kappaB (RANK) protein activates various
protein kinase signaling cascades, including those involving NF-kappaB, mitogen
activated protein kinase (MAPK), and Bruton tyrosine kinase (Btk)/tyrosine
protein kinase Tec. However, the mechanism underlying the negative regulation of
RANK by downstream signaling molecules remains unclear. Here, we report that Src
homology 3 domain and cysteine-rich domain-containing protein 2 (STAC2) is a
novel RANK ligand-inducible protein that negatively regulates RANK-mediated
osteoclast formation. STAC2 physically interacts with RANK and inhibits the
formation of the RANK signaling complex, which contains Grb-2-associated binder 2
(Gab2) and phospholipase Cgamma2 (PLCgamma2), thus leading to the suppression of
RANK-mediated NF-kappaB and MAPK activation. Furthermore, STAC2 overexpression
limits Btk/Tec-mediated PLCgamma2 phosphorylation via the interaction between
STAC2 and Btk/Tec. Taken together, our results reveal a novel mechanism whereby
RANK signaling is restricted by its physical interaction with STAC2.
PMID- 29348676
TI - miR-137 regulates ferroptosis by targeting glutamine transporter SLC1A5 in
melanoma.
AB - Ferroptosis is a regulated form of cell death driven by small molecules or
conditions that induce lipid-based reactive oxygen species (ROS) accumulation.
This form of iron-dependent cell death is morphologically and genetically
distinct from apoptosis, necroptosis, and autophagy. miRNAs are known to play
crucial roles in diverse fundamental biological processes. However, to date no
study has reported miRNA-mediated regulation of ferroptosis. Here we show that
miR-137 negatively regulates ferroptosis by directly targeting glutamine
transporter SLC1A5 in melanoma cells. Ectopic expression of miR-137 suppressed
SLC1A5, resulting in decreased glutamine uptake and malondialdehyde (MDA)
accumulation. Meanwhile, antagomir-mediated inactivation of endogenous miR-137
increased the sensitivity of melanoma cells to erastin- and RSL3-induced
ferroptosis. Importantly, knockdown of miR-137 increased the antitumor activity
of erastin by enhancing ferroptosis both in vitro and in vivo. Collectively,
these data indicate that miR-137 plays a novel and indispensable role in
ferroptosis by inhibiting glutaminolysis and suggest a potential therapeutic
approach for melanoma.
PMID- 29348678
TI - 2017 FDA drug approvals.
PMID- 29348677
TI - The Proliferation Capacity of Cultured Neural Stem Cells Promoted by CSF
Collected from SAH Patients Correlates to Clinical Outcome.
AB - Neurogenesis from endogenous neural stem cells (NSCs) might contribute to
functional recovery after stroke based on animal studies; however, the
relationship between neurogenesis and post-stroke outcome has rarely been
demonstrated in humans. We prospectively collected cerebrospinal fluid (CSF) from
36 patients with subarachnoid hemorrhage (SAH). The CSF was added to the culture
medium of the rat NSCs to test the effects on proliferation (proliferation index
[PI], percentage of Ki-67 immunoreactive cells). We correlated the PI with
functional outcome based on the modified Rankin Scale at 3 months post-SAH.
Treatment with the CSF samples collected from SAH patients showed a higher PI
compared with those collected from patients with normal pressure hydrocephalus
and untreated controls (20.3 +/- 8.8 vs. 8.2 +/- 5.1 and 7.8 +/- 3.0, P < 0.001),
indicating proliferation-promoting factors in CSF after SAH. The PI was
positively correlated with SAH volume (p = 0.025). For patients with lower SAH
volume, patients with favorable outcome had a higher PI than those with poor
outcome (20.8 +/- 6.9 vs. 14.6 +/- 4.3, p = 0.047). Using multivariable logistic
regression analysis, the PI was a positive determinant for favorable outcome
(odds ratio, 1.17; 95% confidence interval, 1.00 to 1.36) that more proliferation
promoting factors in CSF was associated with better functional outcome in SAH
patients.
PMID- 29348679
TI - Market watch: 2017 FDA drug approvals: number rebounds but average value slips.
PMID- 29348680
TI - Morgan Sheng.
PMID- 29348682
TI - Glimmers in illuminating the druggable genome.
PMID- 29348681
TI - Impact of a five-dimensional framework on R&D productivity at AstraZeneca.
AB - In 2011, AstraZeneca embarked on a major revision of its research and development
(R&D) strategy with the aim of improving R&D productivity, which was below
industry averages in 2005-2010. A cornerstone of the revised strategy was to
focus decision-making on five technical determinants (the right target, right
tissue, right safety, right patient and right commercial potential). In this
article, we describe the progress made using this '5R framework' in the hope that
our experience could be useful to other companies tackling R&D productivity
issues. We focus on the evolution of our approach to target validation, hit and
lead optimization, pharmacokinetic/pharmacodynamic modelling and drug safety
testing, which have helped improve the quality of candidate drug nomination, as
well as the development of the right culture, where 'truth seeking' is encouraged
by more rigorous and quantitative decision-making. We also discuss where the
approach has failed and the lessons learned. Overall, the continued evolution and
application of the 5R framework are beginning to have an impact, with success
rates from candidate drug nomination to phase III completion improving from 4% in
2005-2010 to 19% in 2012-2016.
PMID- 29348683
TI - The effect of foreign language in fear acquisition.
AB - Emotions are at the core of human nature. There is evidence that emotional
reactivity in foreign languages compared to native languages is reduced. We
explore whether this emotional distance could modulate fear conditioning, an
essential mechanism for the understanding and treatment of anxiety disorders. A
group of participants was verbally informed (either in a foreign or in a native
language) that two different stimuli could be either cueing the potential
presence of a threat stimulus or its absence. We registered pupil size and
electrodermal activity and calculated the difference in psychophysiological
responses to conditioned and to unconditioned stimuli. Our findings provided
evidence that verbal conditioning processes are affected by language context in
this paradigm. We report the first experimental evidence regarding how the use of
a foreign language may reduce fear conditioning. This observation opens the
avenue to the potential use of a foreign language in clinical contexts.
PMID- 29348684
TI - Mithramycin A suppresses basal triple-negative breast cancer cell survival
partially via down-regulating Kruppel-like factor 5 transcription by Sp1.
AB - As the most malignant breast cancer subtype, triple-negative breast cancer (TNBC)
does not have effective targeted therapies clinically to date. As a selective Sp1
inhibitor, Mithramycin A (MIT) has been reported to have anti-tumor activities in
multiple cancers. However, the efficacy and the mechanism of MIT in breast
cancer, especially TNBC, have not been studied. In this study, we demonstrated
that MIT suppressed breast cancer cell survival in a dosage-dependent manner.
Interestingly, TNBC cells were more sensitive to MIT than non-TNBC cells. MIT
inhibited TNBC cell proliferation and promoted apoptosis in vitro in time- and
dosage-dependent manners. MIT suppressed TNBC cell survival, at least partially,
by transcriptionally down-regulating KLF5, an oncogenic transcription factor
specifically expressed in basal TNBC. Finally, MIT suppressed TNBC cell growth in
a xenograft mouse model. Taken together, our findings suggested that MIT inhibits
basal TNBC via the Sp1/KLF5 axis and that MIT may be used for TNBC treatment.
PMID- 29348685
TI - Overexpression of adhesion molecules and barrier molecules is associated with
differential infiltration of immune cells in non-small cell lung cancer.
AB - Immunotherapy is emerging as a promising option for lung cancer treatment.
Various endothelial adhesion molecules, such as integrin and selectin, as well as
various cellular barrier molecules such as desmosome and tight junctions,
regulate T-cell infiltration in the tumor microenvironment. However, little is
known regarding how these molecules affect immune cells in patients with lung
cancer. We demonstrated for the first time that overexpression of endothelial
adhesion molecules and cellular barrier molecule genes was linked to differential
infiltration of particular immune cells in non-small cell lung cancer.
Overexpression of endothelial adhesion molecule genes is associated with
significantly lower infiltration of activated CD4 and CD8 T-cells, but higher
infiltration of activated B-cells and regulatory T-cells. In contrast,
overexpression of desmosome genes was correlated with significantly higher
infiltration of activated CD4 and CD8 T-cells, but lower infiltration of
activated B-cells and regulatory T-cells in lung adenocarcinoma. This inverse
relation of immune cells aligns with previous studies of tumor-infiltrating B
cells inhibiting T-cell activation. Although overexpression of endothelial
adhesion molecule or cellular barrier molecule genes alone was not predictive of
overall survival in our sample, these genetic signatures may serve as biomarkers
of immune exclusion, or resistance to T-cell mediated immunotherapy.
PMID- 29348687
TI - Far field superfocusing along with enhanced near field emission from hybrid
spiral plasmonic lens inscribed with nano corrals slit diffractor.
AB - Here, we have numerically calculated electric field intensity and phase of the
emission from various hybrid spiral plasmonic lenses (HSPL) in near field as well
as in far-field. We have proposed a novel HSPL inscribed with nano corrals slit
(NCS) and compared its focusing ability with other HSPLs inscribed with circular
slit and circular grating. With the use of nano corrals slit, we have been able
to improve light intensity in the far-field without compromising near-field
intensity. Our NCS-HSPL outperforms other HSPLs and standalone SPL in near-field
as well as far-field. We have also found that proposed circular slit diffractor
is far more superior than previously reported circular grating diffractor. We
have been able to extend the focal length of hybrid plasmonic lens upto 3 um and
observed a two-fold increment in the far field intensity compared to existing
spiral plasmonic lens even though size of focal spot remains same. Optical
complex fields produced by NCS based HSPL can be used for various applications
such as super resolution microscopy, nanolithography, bioimaging and sensing,
angular momentum detectors, etc. Moreover, enhanced near-field intensity in
conjunction with far-field superfocusing with reasonable focal length may lead to
the development of novel multifunctional lab-on-chip devices.
PMID- 29348686
TI - Defects in the mitochondrial-tRNA modification enzymes MTO1 and GTPBP3 promote
different metabolic reprogramming through a HIF-PPARgamma-UCP2-AMPK axis.
AB - Human proteins MTO1 and GTPBP3 are thought to jointly catalyze the modification
of the wobble uridine in mitochondrial tRNAs. Defects in each protein cause
infantile hypertrophic cardiomyopathy with lactic acidosis. However, the
underlying mechanisms are mostly unknown. Using fibroblasts from an MTO1 patient
and MTO1 silenced cells, we found that the MTO1 deficiency is associated with a
metabolic reprogramming mediated by inactivation of AMPK, down regulation of the
uncoupling protein 2 (UCP2) and transcription factor PPARgamma, and activation of
the hypoxia inducible factor 1 (HIF-1). As a result, glycolysis and oxidative
phosphorylation are uncoupled, while fatty acid metabolism is altered, leading to
accumulation of lipid droplets in MTO1 fibroblasts. Unexpectedly, this response
is different from that triggered by the GTPBP3 defect, as GTPBP3-depleted cells
exhibit AMPK activation, increased levels of UCP2 and PPARgamma, and inactivation
of HIF-1. In addition, fatty acid oxidation and respiration are stimulated in
these cells. Therefore, the HIF-PPARgamma-UCP2-AMPK axis is operating differently
in MTO1- and GTPBP3-defective cells, which strongly suggests that one of these
proteins has an additional role, besides mitochondrial-tRNA modification. This
work provides new and useful information on the molecular basis of the MTO1 and
GTPBP3 defects and on putative targets for therapeutic intervention.
PMID- 29348688
TI - Response to correspondence from the ESSA Statement authors.
PMID- 29348689
TI - Response to "The neurogenic bowel dysfunction score in patients with spinal cord
injury: methodological issues in reliability and validity".
PMID- 29348690
TI - The neurogenic bowel dysfunction score in patients with spinal cord injury:
methodological issues in reliability and validity.
PMID- 29348691
TI - Correspondence re "Evidence-based scientific exercise guidelines for adults with
spinal cord injury: an update and new guideline".
PMID- 29348692
TI - Genome-wide search for higher order epistasis as modifiers of treatment effects
on bone mineral density in childhood cancer survivors.
AB - Single-nucleotide polymorphisms (SNPs) contributing to interactions between
regulatory elements that modulate gene transcription may explain some of the
uncharacterized variation for complex traits. We explored this hypothesis among
856 adult survivors of pediatric cancer exposed to curative treatments that
adversely affect bone mineral density (BMD). To restrict our search to
interactions among SNPs in regulatory elements, our analysis considered 75523
SNPs mapped to putative promoter or enhancer regions. In anticipation that power
to detect higher order epistasis would be low using an exhaustive search and a
Bonferroni-corrected threshold for genome-wide significance (e.g., P < 5.6 * 10
14), a novel non-exhaustive statistical algorithm was implemented to detect
chromosome-wide three-way regulatory interactions. We used a permutation-based
evaluation statistic to identify candidate SNP interactions with stronger
associations with BMD than expected. Of the six regulatory 3-SNP interactions
identified as candidate interactions (P < 3.5 * 10-11) among cancer survivors
exposed to treatments, five were replicated in an independent cohort of survivors
(N = 1428) as modifiers of treatment effects on BMD (P < 0.05). Analyses with
publicly available bioinformatics data revealed that SNPs contributing to
replicated interactions were enriched for gene expressions (P = 3.6 * 10-4) and
enhancer states (P < 0.05) in cells relevant for bone biology. For each
replicated interaction, implicated SNPs were within or directly adjacent to 100
kb windows of genomic regions that plausibly physically interact in
lymphoblastoid cells. Our study demonstrates the utility of a hypothesis-driven
approach in revealing epistasis associated with complex traits.
PMID- 29348694
TI - Effect of deliberation on the public's attitudes toward consent policies for
biobank research.
AB - In this study, we evaluate the effect of education and deliberation on the
willingness of members of the public to donate tissue to biobank research and on
their attitudes regarding various biobank consent policies. Participants were
randomly assigned to a democratic deliberation (DD) group, an education group
that received only written materials, and a control group. Participants completed
a survey before the deliberation and two surveys post-deliberation: one on (or
just after) the deliberation day, and one 4 weeks later. Subjects were asked to
rate 5 biobank consent policies as acceptable (or not) and to identify the best
and worst policies. Analyses compared acceptability of different policy options
and changes in attitudes across the three groups. After deliberation, subjects in
the DD group were less likely to find broad consent (defined here as consent for
the use of donations in an unspecified range of future research studies, subject
to content and process restrictions) and study-by-study consent acceptable. The
DD group was also significantly less likely to endorse broad consent as the best
policy (OR = 0.34), and more likely to prefer alternative consent options. These
results raise ethical challenges to the current widespread reliance on broad
consent in biobank research, but do not support study-by-study consent.
PMID- 29348693
TI - Variants in members of the cadherin-catenin complex, CDH1 and CTNND1, cause
blepharocheilodontic syndrome.
AB - Blepharocheilodontic syndrome (BCDS) consists of lagophthalmia, ectropion of the
lower eyelids, distichiasis, euryblepharon, cleft lip/palate and dental anomalies
and has autosomal dominant inheritance with variable expression. We identified
heterozygous variants in two genes of the cadherin-catenin complex, CDH1,
encoding E-cadherin, and CTNND1, encoding p120 catenin delta1 in 15 of 17 BCDS
index patients, as was recently described in a different publication. CDH1 plays
an essential role in epithelial cell adherence; CTNND1 binds to CDH1 and controls
the stability of the complex. Functional experiments in zebrafish and human cells
showed that the CDH1 variants impair the cell adhesion function of the cadherin
catenin complex in a dominant-negative manner. Variants in CDH1 have been linked
to familial hereditary diffuse gastric cancer and invasive lobular breast cancer;
however, no cases of gastric or breast cancer have been reported in our BCDS
cases. Functional experiments reported here indicated the BCDS variants comprise
a distinct class of CDH1 variants. Altogether, we identified the genetic cause of
BCDS enabling DNA diagnostics and counseling, in addition we describe a novel
class of dominant negative CDH1 variants.
PMID- 29348695
TI - Synchronization of Clocks Through 12 km of Strongly Turbulent Air Over a City.
AB - We demonstrate real-time, femtosecond-level clock synchronization across a low
lying, strongly turbulent, 12-km horizontal air path by optical two-way time
transfer. For this long horizontal free-space path, the integrated turbulence
extends well into the strong turbulence regime corresponding to multiple
scattering with a Rytov variance up to 7 and with the number of signal
interruptions exceeding 100 per second. Nevertheless, optical two-way time
transfer is used to synchronize a remote clock to a master clock with femtosecond
level agreement and with a relative time deviation dropping as low as a few
hundred attoseconds. Synchronization is shown for a remote clock based on either
an optical or microwave oscillator and using either tip-tilt or adaptive-optics
free-space optical terminals. The performance is unaltered from optical two-way
time transfer in weak turbulence across short links. These results confirm that
the two-way reciprocity of the free-space time-of-flight is maintained both under
strong turbulence and with the use of adaptive optics. The demonstrated
robustness of optical two-way time transfer against strong turbulence and its
compatibility with adaptive optics is encouraging for future femtosecond clock
synchronization over very long distance ground-to-air free-space paths.
PMID- 29348696
TI - Three-Dimensional Simulations of Tearing and Intermittency in Coronal Jets.
AB - Observations of coronal jets increasingly suggest that local fragmentation and
intermittency play an important role in the dynamics of these events. In this
work we investigate this fragmentation in high-resolution simulations of jets in
the closed-field corona. We study two realizations of the embedded-bipole model,
whereby impulsive helical outflows are driven by reconnection between twisted and
untwisted field across the domed fan plane of a magnetic null. We find that the
reconnection region fragments following the onset of a tearing-like instability,
producing multiple magnetic null points and flux-rope structures within the
current layer. The flux ropes formed within the weak-field region in the center
of the current layer are associated with "blobs" of density enhancement that
become filamentary threads as the flux ropes are ejected from the layer,
whereupon new flux ropes form behind them. This repeated formation and ejection
of flux ropes provides a natural explanation for the intermittent outflows,
bright blobs of emission, and filamentary structure observed in some jets.
Additional observational signatures of this process are discussed. Essentially
all jet models invoke reconnection between regions of locally closed and locally
open field as the jet-generation mechanism. Therefore, we suggest that this
repeated tearing process should occur at the separatrix surface between the two
flux systems in all jets. A schematic picture of tearing-mediated jet
reconnection in three dimensions is outlined.
PMID- 29348697
TI - Optimum Wing Shape Determination of Highly Flexible Morphing Aircraft for
Improved Flight Performance.
AB - In this paper, optimum wing bending and torsion deformations are explored for a
mission adaptive, highly flexible morphing aircraft. The complete highly flexible
aircraft is modeled using a strain-based geometrically nonlinear beam
formulation, coupled with unsteady aerodynamics and 6-dof rigid-body motions.
Since there are no conventional discrete control surfaces for trimming the
flexible aircraft, the design space for searching the optimum wing geometries is
enlarged. To achieve high performance flight, the wing geometry is best tailored
according to the specific flight mission needs. In this study, the steady level
flight and the coordinated turn flight are considered, and the optimum wing
deformations with the minimum drag at these flight conditions are searched by
utilizing a modal-based optimization procedure, subject to the trim and other
constraints. The numerical study verifies the feasibility of the modal-based
optimization approach, and shows the resulting optimum wing configuration and its
sensitivity under different flight profiles.
PMID- 29348698
TI - Effects of FAME biodiesel and HVORD on emissions from an older-technology diesel
engine.
AB - The results of laboratory evaluations were used to compare the potential of two
alternative, biomass-derived fuels as a control strategy to reduce the exposure
of underground miners to aerosols and gases emitted by diesel-powered equipment.
The effects of fatty acid methyl ester (FAME) biodiesel and hydrotreated
vegetable oil renewable diesel (HVORD) on criteria aerosol and gaseous emissions
from an older-technology, naturally aspirated, mechanically controlled engine
equipped with a diesel oxidation catalytic converter were compared with those of
widely used petroleum-derived, ultralow-sulfur diesels (ULSDs). The emissions
were characterized for four selected steady-state conditions. When fueled with
FAME biodiesel and HVORD, the engine emitted less aerosols by total particulate
mass, total carbon mass, elemental carbon mass and total number than when it was
fueled with ULSDs. Compared with ULSDs, FAME biodiesel and HVORD produced
aerosols that were characterized by single modal distributions, smaller count
median diameters, and lower total and peak concentrations. For the majority of
test cases, FAME biodiesel and HVORD favorably affected nitric oxide (NO) and
adversely affected nitrogen dioxide (NO2) generation. Therefore, the use of these
alternative fuels appears to be a viable tool for the underground mining industry
to address the issues related to emissions from diesel engines, and to transition
toward more universal solutions provided by advanced engines with integrated
exhaust after treatment technologies.
PMID- 29348699
TI - Industrial Internet of Things: (IIoT) applications in underground coal mines.
AB - The Industrial Internet of Things (IIoT), a concept that combines sensor networks
and control systems, has been employed in several industries to improve
productivity and safety. U.S. National Institute for Occupational Safety and
Health (NIOSH) researchers are investigating IIoT applications to identify the
challenges of and potential solutions for transferring IIoT from other industries
to the mining industry. Specifically, NIOSH has reviewed existing sensors and
communications network systems used in U.S. underground coal mines to determine
whether they are capable of supporting IIoT systems. The results show that about
40 percent of the installed post-accident communication systems as of 2014
require minimal or no modification to support IIoT applications. NIOSH
researchers also developed an IIoT monitoring and control prototype system using
low-cost microcontroller Wi-Fi boards to detect a door opening on a refuge
alternative, activate fans located inside the Pittsburgh Experimental Mine and
actuate an alarm beacon on the surface. The results of this feasibility study can
be used to explore IIoT applications in underground coal mines based on existing
communication and tracking infrastructure.
PMID- 29348700
TI - Open-air sprays for capturing and controlling airborne float coal dust on
longwall faces.
AB - Float dust deposits in coal mine return airways pose a risk in the event of a
methane ignition. Controlling airborne dust prior to deposition in the return
would make current rock dusting practices more effective and reduce the risk of
coal-dust-fueled explosions. The goal of this U.S. National Institute for
Occupational Safety and Health study is to determine the potential of open-air
water sprays to reduce concentrations of airborne float coal dust, smaller than
75 um in diameter, in longwall face airstreams. This study evaluated unconfined
water sprays in a featureless tunnel ventilated at a typical longwall face
velocity of 3.6 m/s (700 fpm). Experiments were conducted for two nozzle
orientations and two water pressures for hollow cone, full cone, flat fan, air
atomizing and hydraulic atomizing spray nozzles. Gravimetric samples show that
airborne float dust removal efficiencies averaged 19.6 percent for all sprays
under all conditions. The results indicate that the preferred spray nozzle should
be operated at high fluid pressures to produce smaller droplets and move more
air. These findings agree with past respirable dust control research, providing
guidance on spray selection and spray array design in ongoing efforts to control
airborne float dust over the entire longwall ventilated opening.
PMID- 29348701
TI - Statistical Significance and the Dichotomization of Evidence: The Relevance of
the ASA Statement on Statistical Significance and p-values for Statisticians.
PMID- 29348702
TI - Subjective Cognitive Impairment, Depressive Symptoms, and Fatigue after a TIA or
Transient Neurological Attack: A Prospective Study.
AB - Introduction: Subjective cognitive impairment (SCI), depressive symptoms, and
fatigue are common after stroke and are associated with reduced quality of life.
We prospectively investigated their prevalence and course after a transient
ischemic attack (TIA) or nonfocal transient neurological attack (TNA) and the
association with diffusion-weighted imaging (DWI) lesions. Methods: The Cognitive
Failures Questionnaire, Hospital Anxiety and Depression Scale, and Subjective
Fatigue subscale from the Checklist Individual Strength were used to assess
subjective complaints shortly after TIA or TNA and six months later. With
repeated measure analysis, the associations between DWI lesion presence or
clinical diagnosis (TIA or TNA) and subjective complaints over time were
determined. Results: We included 103 patients (28 DWI positive). At baseline, SCI
and fatigue were less severe in DWI positive than in DWI negative patients,
whereas at follow-up, there were no differences. SCI (p = 0.02) and fatigue (p =
0.01) increased in severity only in DWI positive patients. There were no
differences between TIA and TNA. Conclusions: Subjective complaints are highly
prevalent in TIA and TNA patients. The short-term prognosis is not different
between DWI-positive and DWI negative patients, but SCI and fatigue increase in
severity within six months after the event when an initial DWI lesion is present.
PMID- 29348703
TI - Platelet-Released Growth Factors Modulate the Secretion of Cytokines in
Synoviocytes under Inflammatory Joint Disease.
AB - The etiology and pathogenesis of rheumatoid arthritis (RA) are marked by a
complex interplay of various cell populations and is mediated by different
signaling pathways. Traditionally, therapies have primarily focused on pain
relief, reducing inflammation and the recovery of joint function. More recently,
however, researchers have discussed the therapeutic efficacy of autologous
platelet-rich plasma (PRP). The main objective of this work is to examine the
influences of platelet-released growth factor (PRGF) on human synoviocytes under
inflammatory conditions. Additionally, it is checked to which extend treatment
with platelet concentrate influences the release of cytokines form synoviocytes.
For this purpose, an in vitro RA model was created by stimulating the cells with
the TNF-alpha. The release of cytokines was measured by ELISA. The cytokine gene
expression was analyzed by real-time PCR. It has been observed that the
stimulation concentration of 10 ng/ml TNF-alpha resulted in a significantly
increased endogenous secretion and gene expression of IL-6 and TNF-alpha. The
anti-inflammatory effect of PRGF could be confirmed through significant reduction
of TNF-alpha and IL-1beta. An induced inflammatory condition seems to cause PRGF
to inhibit the release of proinflammatory cytokines. Further study is required to
understand the exact effect mechanism of PRGF on synoviocytes.
PMID- 29348705
TI - Proximal extrapolated gradient methods for variational inequalities.
AB - The paper concerns with novel first-order methods for monotone variational
inequalities. They use a very simple linesearch procedure that takes into account
a local information of the operator. Also, the methods do not require Lipschitz
continuity of the operator and the linesearch procedure uses only values of the
operator. Moreover, when the operator is affine our linesearch becomes very
simple, namely, it needs only simple vector-vector operations. For all our
methods, we establish the ergodic convergence rate. In addition, we modify one of
the proposed methods for the case of a composite minimization. Preliminary
results from numerical experiments are quite promising.
PMID- 29348704
TI - Stimulation of Alpha7 Nicotinic Acetylcholine Receptor Attenuates Nicotine
Induced Upregulation of MMP, MCP-1, and RANTES through Modulating ERK1/2/AP-1
Signaling Pathway in RAW264.7 and MOVAS Cells.
AB - Vagus nerve stimulation through alpha7 nicotine acetylcholine receptors (alpha7
nAChR) signaling had been demonstrated attenuation of inflammation. This study
aimed to determine whether PNU-282987, a selective alpha7-nAChR agonist, affected
activities of matrix metalloproteinase (MMP) and inflammatory cytokines in
nicotine-treatment RAW264.7 and MOVAS cells and to assess the underlying
molecular mechanisms. RAW264.7 and MOVAS cells were treated with nicotine at
different concentrations (0, 1, 10, and 100 ng/ml) for 0-120 min. Nicotine
markedly stimulated the phosphorylation of extracellular signal-regulated
kinase1/2 (ERK1/2) and c-Jun in RAW264.7 cells. Pretreatment with U0126
significantly suppressed phosphorylation of ERK1/2 and further attenuated
nicotine-induced activation of c-Jun and upregulation of MMP-2, MMP-9, monocyte
chemotactic protein- (MCP-) 1, and regulated upon activation normal T cell
expressed and secreted (RANTES). Similarly, nicotine treatment also increased
phosphorylation of c-Jun and expressions of MMP-2, MMP-9, MCP-1, and RANTES in
MOVAS cells. When cells were pretreated with PNU-282987, nicotine-induced
activations of ERK1/2 and c-Jun in RAW264.7 cells and c-Jun in MOVAS cells were
effectively inhibited. Furthermore, nicotine-induced secretions of MMP-2, MMP-9,
MCP-1, and RANTES were remarkably downregulated. Treatment with alpha7-nAChR
agonist inhibits nicotine-induced upregulation of MMP and inflammatory cytokines
through modulating ERK1/2/AP-1 signaling in RAW264.7 cells and AP-1 in MOVAS
cells, providing a new therapeutic for abdominal aortic aneurysm.
PMID- 29348706
TI - Diagnosis and Treatment of Clostridium difficile Infection (CDI).
AB - Early and accurate diagnosis is essential for optimal treatment of individuals
with Clostridium difficile infection (CDI) and for implementation of effective
infection control procedures. The decision about which diagnostic test to use is
an important one that should be based on test sensitivity, specificity, and
predictive value. The challenges of CDI go beyond rapid identification and
management of symptomatic patients. Asymptomatic carriage has long been suspected
in C. difficile transmission, but it may play a larger role than previously
thought. Emerging information also shows that patients treated for CDI remain
colonized for many weeks after symptom resolution. In fact, stool culture
positivity increases during the first weeks following treatment completion.
Treatments that reduce the duration and degree of asymptomatic shedding could
have added benefit for reduced transmission.
PMID- 29348707
TI - Evolution of Knowledge, Awareness, and Practices regarding Zika Virus from 2016
to 2017.
AB - Objective: Our team created a knowledge, attitudes, and practice (KAP) survey in
order to assess changes over time in healthcare provider and community member
awareness of Zika virus symptoms, transmission, treatment, and current and future
concerns. Study Design: The cross-sectional survey was issued at an academic
medical center in Washington, DC, and via an online link to healthcare providers
and community members between June and August 2016. Survey distribution was then
repeated the following year, from March to April 2017. Outcomes were compared by
survey year and healthcare provider versus community member status using SAS
Program Version 9.4. Results: Significant differences in knowledge, attitudes,
and practices existed between 2016 and 2017 survey time points. By 2017, more
respondents had knowledge of various Zika virus infection characteristics;
however healthcare provider knowledge also waned in certain areas. Attitudes
towards Zika virus infection displayed an overall decreased concern by 2017.
Practice trends by 2017 demonstrated fewer travel restrictions to Zika-endemic
areas and increased mosquito protective measures within the US. Conclusions: Our
results provide novel insight into the transformation of knowledge, attitudes,
and practice of community members and healthcare providers regarding Zika virus
since its declaration as a public health emergency of international concern in
2016.
PMID- 29348708
TI - HybPhyloMaker: Target Enrichment Data Analysis From Raw Reads to Species Trees.
AB - Summary: Hybridization-based target enrichment in combination with genome
skimming (Hyb-Seq) is becoming a standard method of phylogenomics. We developed
HybPhyloMaker, a bioinformatics pipeline that performs target enrichment data
analysis from raw reads to supermatrix-, supertree-, and multispecies coalescent
based species tree reconstruction. HybPhyloMaker is written in BASH and
integrates common bioinformatics tools. It can be launched both locally and on a
high-performance computer cluster. Compared with existing target enrichment data
analysis pipelines, HybPhyloMaker offers the following main advantages:
implementation of all steps of data analysis from raw reads to species tree
reconstruction, calculation and summary of alignment and gene tree properties
that assist the user in the selection of "quality-filtered" genes, implementation
of several species tree reconstruction methods, and analysis of the coding
regions of organellar genomes. Availability: The HybPhyloMaker scripts, manual as
well as a test data set, are available in https://github.com/tomas
fer/HybPhyloMaker/. HybPhyloMaker is licensed under open-source license GPL v.3
allowing further modifications.
PMID- 29348709
TI - Perioperative Medicine: A Burgeoning Field with Profound Importance to a Modern
Clinician.
AB - AIMS AND SCOPE This article serves in introducing the readers to the developing
field of perioperative medicine. We have made an effort to come up with the
latest management guidelines covering multiple subspecialties in form of a
special supplement. This compendium in perioperative medicine serves as a
comprehensive guide to a practicing clinician, in managing patients with various
medical comorbidities undergoing surgical procedures and avoiding common
pitfalls.
PMID- 29348711
TI - Efficacy of Empirical Therapy With Combined Ciprofloxacin Versus Topical Drops
Alone in Patients With Tubotympanic Chronic Suppurative Otitis Media: A
Randomized Double-Blind Controlled Trial.
AB - Background: One of the prevailing otologic infections in our country is chronic
suppurative otitis media, especially the tubotympanic type for which various
treatment protocols are followed. Usually, oral and topical antibiotics (mainly
quinolones) are given alone or in combination. There is a lack of consensus as to
whether topical drops alone are effective or a combined oral and systemic therapy
should be prescribed. In our study, we have attempted to observe the efficacy of
empirical therapy with combined ciprofloxacin versus topical drops only in
patients with tubotympanic chronic suppurative otitis media for control of
infection. Methodology: A total of 100 patients visiting the outpatient ENT
department at our tertiary care hospital with clinically diagnosed chronic
suppurative otitis media (tubotympanic type) were enrolled in our study. The
study was reviewed and accepted by the ethical review committee. A detailed
proforma was filled for all patients. All patients after aural toilet were
subjected randomly to one of the 2 treatment methods, ie, topical ciprofloxacin
ear drops plus an oral placebo or combined oral and topical ciprofloxacin. These
patients were reviewed after 1 week of treatment. Results: It was observed that
48 of 50 (96%) patients responded to treatment in the group receiving topical
ciprofloxacin, whereas 49 of 50 (98%) patients responded in the group receiving
combined therapy. This difference was not significant. Moreover, age, sex, and
duration of discharge did not have any effect on treatment. There were minimal
side effects in both groups, which were also not significant and disappeared
after discontinuation of treatment. Conclusions: The results of this study show
that topical ciprofloxacin drops were as effective as combined oral and topical
ciprofloxacin and that the addition of oral drug did not have any beneficial
effect and added only to the cost of treatment.
PMID- 29348710
TI - The Protein Tyrosine Phosphatase Nonreceptor 22 (PTPN22) R620W Functional
Polymorphism in Psoriasis.
AB - Background: Psoriasis is a complex autoimmune disease caused by the interaction
of genetic and environmental factors. PTPN22 gene polymorphism has been reported
to affect psoriasis susceptibility; however, no data are available for Middle
Eastern populations. Objective: The aim of this study was to investigate the
association of PTPN22 (1858C/T) R620W polymorphism with psoriasis in a Saudi
cohort. Methods: Saudi subjects (n = 306) including patients with psoriasis (n =
106) and matched controls (n = 200) were studied for PTPN22 variants using tetra
primer amplification refractory mutation system-polymerase chain reaction method.
The frequencies of alleles and genotypes of PTPN22 (1858C/T) polymorphism were
compared between patients and controls. Results: The frequency of CT genotype of
PTPN22 (1858C/T) polymorphism was significantly higher, whereas that of CC
genotype was lower in patients with psoriasis than in controls (P < .001,
relative risk [RR] = 7.151). The homozygous genotype TT was absent in both the
patients and healthy controls. The frequency of allele T encoding tryptophan (W)
was significantly increased (P < .001, RR = 5.76), whereas that of allele C
encoding arginine (R) decreased in psoriasis cases as compared with controls (P <
.001, RR = 0.173) indicating that individuals carrying allele T are more
susceptible to psoriasis than noncarriers. Conclusions: PTPN22 (1858C/T)
polymorphism is positively associated with susceptibility of psoriasis in Saudis
and can be developed as biomarker for evaluating psoriasis risk. However, further
studies on PTPN22 polymorphism in larger samples from different geographical
areas and ethnicity are warranted.
PMID- 29348712
TI - Assessment of Ramadan Education and Knowledge Among Diabetic Patients.
AB - Background: During Ramadan, Muslims fast from dawn until dusk for one lunar month
every year. Most of the Muslim patients with diabetes are unaware of the
potential complications that can occur while fasting, such as hypoglycemia. The
aim of this study is to assess the the patient education level and patients'
overall awareness of any possible complications that could occur while fasting
during Ramadan and to determine how these patients deal with these complications.
Methods: We conducted a cross-sectional study and surveyed diabetic patients
about their diabetes-related knowledge over a period of 4 months from the
outpatient clinic at the Obesity, Endocrine, and Metabolism Center at King Fahad
Medical City. Patients were included if they were >=16 years and if they had been
receiving treatment for at least 1 year before the study, irrespective of the
medications used; patients were also asked about the presence or absence of
complications. Results: This study included 477 patients (325 women and 152 men).
Most patients (297; 62.3%) had type 2 diabetes. The patients' mean age was 39.72
+/- 15.29 years, and the mean duration of diabetes was 10.80 +/- 5.88 years.
During the preceding Ramadan, 76% of patients reported fasting, whereas 58% said
that they monitored their blood glucose levels once per day. Hypoglycemic
episodes were reported in 60.3% of cases with type 2 diabetes and in 8.3% of
cases with type 1 diabetes. Among those who had hypoglycemia, 2.8% of patients
with type 1 diabetes and 17.8% with type 2 diabetes broke their fast. Finally,
54% of patients reported that their health care providers offered them
instructions on diabetes management during Ramadan. Conclusions: Ramadan health
education in diabetes can encourage, improve, and guide patients to change their
lifestyles during Ramadan while minimizing the risk of acute complications.
PMID- 29348713
TI - Disentangling the Sleep-Pain Relationship in Pediatric Chronic Pain: The
Mediating Role of Internalizing Mental Health Symptoms.
AB - Background: Pediatric chronic pain often emerges in adolescence and cooccurs with
internalizing mental health issues and sleep impairments. Emerging evidence
suggests that sleep problems may precede the onset of chronic pain as well as
anxiety and depression. Studies conducted in pediatric populations with pain
related chronic illnesses suggest that internalizing mental health symptoms may
mediate the sleep-pain relationship; however, this has not been examined in youth
with primary pain disorders. Objective: To examine whether anxiety and depressive
symptoms mediated relationships between sleep quality and pain outcomes among
youth with chronic pain. Methods: Participants included 147 youth (66.7% female)
aged 8-18 years who were referred to a tertiary-level chronic pain program. At
intake, the youth completed psychometrically sound measures of sleep quality,
pain intensity, pain interference, and anxiety and depressive symptoms. Results:
As hypothesized, poor sleep quality was associated with increased pain intensity
and pain interference, and anxiety and depressive symptoms mediated these sleep
pain relationships. Discussion: For youth with chronic pain, poor sleep quality
may worsen pain through alterations in mood and anxiety; however, prospective
research using objective measures is needed. Future research should examine
whether targeting sleep and internalizing mental health symptoms in treatments
improve pain outcomes in these youth.
PMID- 29348714
TI - Orofacial Pains.
PMID- 29348715
TI - Ginseng and obesity.
AB - Although ginseng has been shown to have an antiobesity effect, antiobesity
related mechanisms are complex and have not been completely elucidated. In the
present study, we evaluated ginseng's effects on food intake, the digestion, and
absorption systems, as well as liver, adipose tissue, and skeletal muscle in
order to identify the mechanisms involved. A review of previous in vitro and in
vivo studies revealed that ginseng and ginsenosides can increase energy
expenditure by stimulating the adenosine monophosphate-activated kinase pathway
and can reduce energy intake. Moreover, in high fat diet-induced obese and
diabetic individuals, ginseng has shown a two-way adjustment effect on
adipogenesis. Nevertheless, most of the previous studies into antiobesity effects
of ginseng have been animal based, and there is a paucity of evidence supporting
the suggestion that ginseng can exert an antiobesity effect in humans.
PMID- 29348716
TI - Cylindrocarpon destructans/Ilyonectria radicicola-species complex: Causative
agent of ginseng root-rot disease and rusty symptoms.
AB - Cylindrocarpon destructans/Ilyonectria radicicola is thought to cause both rusty
symptom and root-rot disease of American and Korean ginseng. Root-rot disease
poses a more serious threat to ginseng roots than rusty symptoms, which we argue
result from the plant defense response to pathogen attack. Therefore, strains
causing rotten root are characterized as more aggressive than strains causing
rusty symptoms. In this review, we state 1- the molecular evidence indicating
that the root-rot causing strains are genetically distinct considering them as a
separate species of Ilyonectria, namely I. mors-panacis and 2- the physiological
and biochemical differences between the weakly and highly aggressive species as
well as those between rusty and rotten ginseng plants. Eventually, we postulated
that rusty symptom occurs on ginseng roots due to incompatible interactions with
the weakly aggressive species of Ilyonectria, by the established iron-phenolic
compound complexes while root-rot is developed by I. mors-panacis infection due
to the production of high quantities of hydrolytic and oxidative fungal enzymes
which destroy the plant defensive barriers, in parallel with the pathogen growth
stimulation by utilizing the available iron. Furthermore, we highlight future
areas for study that will help elucidate the complete mechanism of root-rot
disease development.
PMID- 29348717
TI - High-performance liquid chromatography analysis of phytosterols in Panax ginseng
root grown under different conditions.
AB - Background: The Panax ginseng plant is used as an herbal medicine. Phytosterols
of P. ginseng have inhibitory effects on inflammation-related factors in HepG2
cells. Methods: Phytosterols (e.g., stigmasterol and beta-sitosterol) in the
roots of P. ginseng grown under various conditions were analyzed using high
performance liquid chromatography. The P. ginseng roots analyzed in this study
were collected from three cultivation areas in Korea (i.e., Geumsan, Yeongju, and
Jinan) and differed by cultivation year (i.e., 4 years, 5 years, and 6 years) and
production process (i.e., straight ginseng, red ginseng, and white ginseng).
Results: The concentrations of stigmasterol and beta-sitosterol in P. ginseng
roots were 2.22-23.04 mg/g and 7.35-59.09 mg/g, respectively. The highest
concentrations of stigmasterol and beta-sitosterol were in the roots of 6-year
old P. ginseng cultivated in Jinan (82.14 mg/g and 53.23 mg/g, respectively).
Conclusion: Six-year-old white ginseng and white ginseng cultivated in Jinan
containing stigmasterol and beta-sitosterol are potentially a new source of
income in agriculture.
PMID- 29348718
TI - Qualitative and quantitative analysis of furosine in fresh and processed
ginsengs.
AB - Background: Furosine (E-N-2-furoylmethyl-L-lysine, FML) is an amino acid
derivative, which is considered to be an important indicator of the extent of
damage (deteriorating the quality of amino acid and proteins due to a blockage of
lysine and a decrease in the digestibility of proteins) during the early stages
of the Maillard reaction. In addition, FML has been proven to be harmful because
it is closely related to a variety of diseases such as diabetes. The qualitative
analysis of FML in fresh and processed ginsengs was confirmed using HPLC-MS.
Methods: An ion-pair reversed-phase LC method was used for the quantitative
analysis of FML in various ginseng samples. Results: The contents of FML in the
ginseng samples were 3.35-42.28 g/kg protein. The lowest value was observed in
the freshly collected ginseng samples, and the highest value was found in the
black ginseng concentrate. Heat treatment and honey addition significantly
increased the FML content from 3.35 g/kg protein to 42.28 g/kg protein.
Conclusion: These results indicate that FML is a promising indicator to estimate
the heat treatment degree and honey addition level during the manufacture of
ginseng products. The FML content is also an important parameter to identity the
quality of ginseng products. In addition, the generation and regulation of
potentially harmful Maillard reaction products-FML in ginseng processing was also
investigated, providing a solid theoretical foundation and valuable reference for
safe ginseng processing.
PMID- 29348719
TI - Effects of processing method on the pharmacokinetics and tissue distribution of
orally administered ginseng.
AB - Background: The use of different methods for the processing of ginseng can result
in alterations in its medicinal properties and efficacy. White ginseng (WG),
frozen ginseng (FG), and red ginseng (RG) are produced using different methods.
WG, FG, and RG possess different pharmacological properties. Methods: WG, FG, and
RG extracts and pure ginsenosides were administered to rats to study the
pharmacokinetics and tissue distribution characteristics of the following
ginsenosides-Rg1, Re, Rb1, and Rd. The concentrations of the ginsenosides in the
plasma and tissues were determined using UPLC-MS/MS. Results: The rate and extent
of absorption of Rg1, Re, Rb1, and Rd appeared to be affected by the different
methods used in processing the ginseng samples. The areas under the plasma drug
concentration-time curves (AUCs) of Rg1, Re, Rb1, and Rd were significantly
higher than those of the pure ginsenosides. In addition, the AUCs of Rg1, Re,
Rb1, and Rd were different for WG, FG, and RG. The amounts of Rg1, Re, Rd, and
Rb1 were significantly (p < 0.05) higher in the tissues than those of the pure
ginsenosides. The amounts of Re, Rb1, and Rd from the RG extract were
significantly higher than those from the WG and FG extracts in the heart, lungs,
and kidneys of the rats. Conclusion: Our results show that the use of different
methods to process ginseng might affect the pharmacokinetics and oral
bioavailability of ginseng as well as the tissue concentrations of Rg1, Re, Rd,
and Rb1.
PMID- 29348720
TI - Gintonin absorption in intestinal model systems.
AB - Background: Recently, we identified a novel ginseng-derived lysophosphatidic acid
receptor ligand, called gintonin. We showed that gintonin induces [Ca2+]i
transient-mediated morphological changes, proliferation, and migration in cells
expressing lysophosphatidic acid receptors and that oral administration of
gintonin exhibits anti-Alzheimer disease effects in model mice. However, little
is known about the intestinal absorption of gintonin. The aim of this study was
to investigate gintonin absorption using two model systems. Methods: Gintonin
membrane permeation was examined using a parallel artificial membrane permeation
assay, and gintonin absorption was evaluated in a mouse everted intestinal sac
model. Results: The parallel artificial membrane permeation assay showed that
gintonin could permeate an artificial membrane in a dose-dependent manner. In the
everted sac model, gintonin absorption increased with incubation time (from 0 min
to 60 min), followed by a decrease in absorption. Gintonin absorption into
everted sacs was also dose dependent, with a nonlinear correlation between
gintonin absorption and concentration at 0.1-3 mg/mL and saturation at 3-5 mg/mL.
Gintonin absorption was inhibited by the Rho kinase inhibitor Y-27632 and the
sodium-glucose transporter inhibitor phloridzin. Moreover, lipid extraction with
methanol also attenuated gintonin absorption, suggesting the importance of the
lipid portion of gintonin in absorption. This result shows that gintonin might be
absorbed through passive diffusion, paracellular, and active transport pathways.
Conclusion: The present study shows that gintonin could be absorbed in the
intestine through transcellular and paracellular diffusion, and active transport.
In addition, the lipid component of gintonin might play a key role in its
intestinal absorption.
PMID- 29348721
TI - Rare ginsenoside Ia synthesized from F1 by cloning and overexpression of the UDP
glycosyltransferase gene from Bacillus subtilis: synthesis, characterization, and
in vitro melanogenesis inhibition activity in BL6B16 cells.
AB - Background: Ginsenoside F1 has been described to possess skin-whitening effects
on humans. We aimed to synthesize a new ginsenoside derivative from F1 and
investigate its cytotoxicity and melanogenesis inhibitory activity in B16BL6
cells using recombinant glycosyltransferase enzyme. Glycosylation has the
advantage of synthesizing rare chemical compounds from common compounds with
great ease. Methods: UDP-glycosyltransferase (BSGT1) gene from Bacillus subtilis
was selected for cloning. The recombinant glycosyltransferase enzyme was
purified, characterized, and utilized to enzymatically transform F1 into its
derivative. The new product was characterized by NMR techniques and evaluated by
MTT, melanin count, and tyrosinase inhibition assay. Results: The new derivative
was identified as (20S)-3beta,6alpha,12beta,20-tetrahydroxydammar-24-ene-20-O
beta-D-glucopyranosyl-3-O-beta-D-glucopyranoside (ginsenoside Ia), which
possesses an additional glucose linked into the C-3 position of substrate F1. Ia
had been previously reported; however, no in vitro biological activity was
further examined. This study focused on the mass production of arduous
ginsenoside Ia from accessible F1 and its inhibitory effect of melanogenesis in
B16BL6 cells. Ia showed greater inhibition of melanin and tyrosinase at 100
MUmol/L than F1 and arbutin. These results suggested that Ia decreased cellular
melanin synthesis in B16BL6 cells through downregulation of tyrosinase activity.
Conclusion: To our knowledge, this is the first study to report on the mass
production of rare ginsenoside Ia from F1 using recombinant UDP
glycosyltransferase isolated from B. subtillis and its superior melanogenesis
inhibitory activity in B16BL6 cells as compared to its precursor. In brief,
ginsenoside Ia can be applied for further study in cosmetics.
PMID- 29348722
TI - Regulatory effects of saponins from Panax japonicus on colonic epithelial tight
junctions in aging rats.
AB - Background: Saponins from Panax japonicus (SPJ) are the most abundant and main
active components of P. japonicus, which replaces ginseng roots in treatment for
many kinds of diseases in the minority ethnic group in China. Our previous
studies have demonstrated that SPJ has the effects of anti-inflammation through
the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF
kappaB) signaling pathways. The present study was designed to investigate whether
SPJ can modulate intestinal tight junction barrier in aging rats and further to
explore the potential mechanism. Methods: Aging rats had been treated with
different doses (10 mg/kg, 30 mg/kg, and 60 mg/kg) of SPJ for 6 mo since they
were 18 mo old. After the rats were euthanized, the colonic samples were
harvested. Levels of tight junctions (claudin-1 and occludin) were determined by
immunohistochemical staining. Levels of proinflammatory cytokines (interleukin
1beta and tumor necrosis factor-alpha) were examined by Western blot. NF-kappaB
and phosphorylation of MAPK signaling pathways were also determined by Western
blot. Results: We found that SPJ increased the expression of the tight junction
proteins claudin-1 and occludin in the colon of aging rats. Treatment with SPJ
decreased the levels of interleukin-1beta and tumor necrosis factor-alpha,
reduced the phosphorylation of three MAPK isoforms, and inhibited the expression
of NF-kappaB in the colon of aging rats. Conclusion: The studies demonstrated
that SPJ modulates the damage of intestinal epithelial tight junction in aging
rats, inhibits inflammation, and downregulates the phosphorylation of the MAPK
and NF-kappaB signaling pathways.
PMID- 29348723
TI - Metabolite profiling of fermented ginseng extracts by gas chromatography mass
spectrometry.
AB - Background: Ginseng contains many small metabolites such as amino acids, fatty
acids, carbohydrates, and ginsenosides. However, little is known about the
relationships between microorganisms and metabolites during the entire ginseng
fermentation process. We investigated metabolic changes during ginseng
fermentation according to the inoculation of food-compatible microorganisms.
Methods: Gas chromatography mass spectrometry (GC-MS) datasets coupled with the
multivariate statistical method for the purpose of latent-information extraction
and sample classification were used for the evaluation of ginseng fermentation.
Four different starter cultures (Saccharomyces bayanus, Bacillus subtilis,
Lactobacillus plantarum, and Leuconostoc mesenteroide) were used for the ginseng
extract fermentation. Results: The principal component analysis score plot and
heat map showed a clear separation between ginseng extracts fermented with S.
bayanus and other strains. The highest levels of fructose, maltose, and galactose
in the ginseng extracts were found in ginseng extracts fermented with B.
subtilis. The levels of succinic acid and malic acid in the ginseng extract
fermented with S. bayanus as well as the levels of lactic acid, malonic acid, and
hydroxypruvic acid in the ginseng extract fermented with lactic acid bacteria (L.
plantarum and L. mesenteroide) were the highest. In the results of taste features
analysis using an electronic tongue, the ginseng extracts fermented with lactic
acid bacteria were significantly distinguished from other groups by a high index
of sour taste probably due to high lactic acid contents. Conclusion: These
results suggest that a metabolomics approach based on GC-MS can be a useful tool
to understand ginseng fermentation and evaluate the fermentative characteristics
of starter cultures.
PMID- 29348724
TI - Ginsenoside Rg3 promotes inflammation resolution through M2 macrophage
polarization.
AB - Background: Ginsenosides have been reported to have many health benefits,
including anti-inflammatory effects, and the resolution of inflammation is now
considered to be an active process driven by M2-type macrophages. In order to
determine whether ginsenosides modulate macrophage phenotypes to reduce
inflammation, 11 ginsenosides were studied with respect to macrophage
polarization and the resolution of inflammation. Methods: Mouse peritoneal
macrophages were polarized into M1 or M2 phenotypes. Reverse transcription
polymerase chain reaction, Western blotting, and measurement of nitric oxide (NO)
and prostaglandin E2 levels were performed in vitro and in a zymosan-induced
peritonitis C57BL/6 mouse model. Results: Ginsenoside Rg3 was identified as a
proresolving ginseng compound based on the induction of M2 macrophage
polarization. Ginsenoside Rg3 not only induced the expression of arginase-1 (a
representative M2 marker gene), but also suppressed M1 marker genes, such as
inducible NO synthase, and NO levels. The proresolving activity of ginsenoside
Rg3 was also observed in vivo in a zymosan-induced peritonitis model. Ginsenoside
Rg3 accelerated the resolution process when administered at peak inflammatory
response into the peritoneal cavity. Conclusion: These results suggest that
ginsenoside Rg3 induces the M2 polarization of macrophages and accelerates the
resolution of inflammation. This finding opens a new avenue in ginseng
pharmacology.
PMID- 29348725
TI - Protective effect of ginsenoside Rb1 against tacrolimus-induced apoptosis in
renal proximal tubular LLC-PK1 cells.
AB - Background: The aim of the present study was to evaluate the potential protective
effects of six ginsenosides (Rb1, Rb2, Rc, Rd, Rg1, and Rg3) isolated from Panax
ginseng against tacrolimus (FK506)-induced apoptosis in renal proximal tubular
LLC-PK1 cells. Methods: LLC-PK1 cells were treated with FK506 and ginsenosides,
and cell viability was measured. Protein expressions of mitogen-activated protein
kinases, caspase-3, and kidney injury molecule-1 (KIM-1) were evaluated by
Western blotting analyses. The number of apoptotic cells was measured using an
image-based cytometric assay. Results: Reduction in cell viability by 60MUM FK506
was ameliorated significantly by cotreatment with ginsenosides Rg1 and Rb1. The
phosphorylation of p38, extracellular signal-regulated kinases, and KIM-1, and
cleavage of caspase-3, increased markedly in LLC-PK1 cells treated with FK506 and
significantly decreased after cotreatment with ginsenoside Rb1. The number of
apoptotic cells decreased by 6.0% after cotreatment with ginsenoside Rb1 (10MUM
and 50MUM). Conclusion: The antiapoptotic effects of ginsenoside Rb1 on FK506
induced apoptosis were mediated by the inhibition of mitogen-activated protein
kinases and caspase activation.
PMID- 29348726
TI - Photoaging protective effects of BIOGF1K, a compound-K-rich fraction prepared
from Panax ginseng.
AB - Background: BIOGF1K, a compound-K-rich fraction, has been shown to display anti
inflammatory activity. Although Panax ginseng is widely used for the prevention
of photoaging events induced by UVB irradiation, the effect of BIOGF1K on
photoaging has not yet been examined. In this study, we investigated the effects
of BIOGF1K on UVB-induced photoaging events. Methods: We analyzed the ability of
BIOGF1K to prevent UVB-induced apoptosis, enhance matrix metalloproteinase (MMP)
expression, upregulate anti-inflammatory activity, reduce sirtuin 1 expression,
and melanin production using reverse transcription-polymerase chain reaction,
melanin content assay, tyrosinase assay, and flow cytometry. We also evaluated
the effects of BIOGF1K on the activator protein-1 signaling pathway, which plays
an important role in photoaging, by immunoblot analysis and luciferase reporter
gene assays. Results: Treatment of UVB-irradiated NIH3T3 fibroblasts with BIOGF1K
prevented UVB-induced cell death, inhibited apoptosis, suppressed morphological
changes, reduced melanin secretion, restored the levels of type I procollagen and
sirtuin 1, and prevented mRNA upregulation of MMP-1, MMP-2, and cyclo-oxygenase
2; these effects all occurred in a dose-dependent manner. In addition, BIOGF1K
markedly reduced activator-protein-1-mediated luciferase activity and decreased
the activity of mitogen-activated protein kinases (extracellular response kinase,
p38, and C-Jun N-terminal kinase). Conclusion: Our results strongly suggest that
BIOGF1K has anti-photoaging activity and that BIOGF1K could be used in anti-aging
cosmeceutical preparations.
PMID- 29348727
TI - Efficacy and safety of Panax ginseng berry extract on glycemic control: A 12-wk
randomized, double-blind, and placebo-controlled clinical trial.
AB - Background: Antihyperglycemic effects of Panax ginseng berry have never been
explored in humans. The aims of this study were to assess the efficacy and safety
of a 12-wk treatment with ginseng berry extract in participants with a fasting
glucose level between 100 mg/dL and 140 mg/dL. Methods: This study was a 12-wk,
randomized, double-blind, placebo-controlled clinical trial. A total of 72
participants were randomly allocated to two groups of either ginseng berry
extract or placebo, and 63 participants completed the study. The parameters
related to glucose metabolism were assessed. Results: Although the present study
failed to show significant antihyperglycemic effects of ginseng berry extract on
the parameters related to blood glucose and lipid metabolism in the total study
population, it demonstrated that ginseng berry extract could significantly
decrease serum concentration of fasting glucose by 3.7% (p = 0.035), postprandial
glucose at 60 min during 75 g oral glucose tolerance test by 10.7% (p = 0.006),
and the area under the curve for glucose by 7.7% (p = 0.024) in those with
fasting glucose level of 110 mg/dL or higher, while the placebo group did not
exhibit a statistically significant decrease. Safety profiles were not different
between the two groups. Conclusion: The present study suggests that ginseng berry
extract has the potential to improve glucose metabolism in human, especially in
those with fasting glucose level of 110 mg/dL or higher. For a more meaningful
benefit, further research in people with higher blood glucose levels is required.
PMID- 29348728
TI - Systems-level mechanisms of action of Panax ginseng: a network pharmacological
approach.
AB - Panax ginseng has been used since ancient times based on the traditional Asian
medicine theory and clinical experiences, and currently, is one of the most
popular herbs in the world. To date, most of the studies concerning P. ginseng
have focused on specific mechanisms of action of individual constituents.
However, in spite of many studies on the molecular mechanisms of P. ginseng, it
still remains unclear how multiple active ingredients of P. ginseng interact with
multiple targets simultaneously, giving the multidimensional effects on various
conditions and diseases. In order to decipher the systems-level mechanism of
multiple ingredients of P. ginseng, a novel approach is needed beyond
conventional reductive analysis. We aim to review the systems-level mechanism of
P. ginseng by adopting novel analytical framework-network pharmacology. Here, we
constructed a compound-target network of P. ginseng using experimentally
validated and machine learning-based prediction results. The targets of the
network were analyzed in terms of related biological process, pathways, and
diseases. The majority of targets were found to be related with primary metabolic
process, signal transduction, nitrogen compound metabolic process, blood
circulation, immune system process, cell-cell signaling, biosynthetic process,
and neurological system process. In pathway enrichment analysis of targets,
mainly the terms related with neural activity showed significant enrichment and
formed a cluster. Finally, relative degrees analysis for the target-disease
association of P. ginseng revealed several categories of related diseases,
including respiratory, psychiatric, and cardiovascular diseases.
PMID- 29348729
TI - Panax ginseng exerts antidepressant-like effects by suppressing neuroinflammatory
response and upregulating nuclear factor erythroid 2 related factor 2 signaling
in the amygdala.
AB - Background: Depression is one of the most commonly diagnosed neuropsychiatric
diseases, but the underlying mechanism and medicine are not well-known. Although
Panax ginseng has been reported to exert protective effects in various
neurological studies, little information is available regarding its
antidepressant effects. Methods: Here, we examined the antidepressant effect and
underlying mechanism of P. ginseng extract (PGE) in a chronic restraint stress
(CRS)-induced depression model in mice. Results: Oral administration of PGE for
14 d decreased immobility (depression-like behaviors) time in forced swim and
tail suspended tests after CRS induction, which corresponded with attenuation of
the levels of serum adrenocorticotropic hormone and corticosterone, as well as
attenuated c-Fos expression in the amygdala. PGE enhanced messenger RNA
expression level of brain-derived neurotrophic factor but ameliorated microglial
activation and neuroinflammation (the level of messenger RNA and protein
expression of cyclooxygenase-2 and inducible nitric oxide synthase) in the
amygdala of mice after CRS induction. Interestingly, 14-d treatment with
celecoxib, a selective cyclooxygenase-2 inhibitor, and Nomega-nitro-L-arginine
methyl ester hydrochloride, a selective inducible nitric oxide synthase
inhibitor, attenuated depression-like behaviors after CRS induction.
Additionally, PGE inhibited the upregulation of the nuclear factor erythroid 2
related factor 2 and heme oxygenase-1 pathways. Conclusion: Taken together, our
findings suggest that PGE exerts antidepressant-like effect of CRS-induced
depression by antineuroinflammatory and antioxidant (nuclear factor erythroid 2
related factor 2/heme oxygenase-1 activation) activities by inhibiting the
hypothalamo-pituitary-adrenal axis mechanism. Further studies are needed to
evaluate the potential of components of P. ginseng as an alternative treatment of
depression, including clinical trial evaluation.
PMID- 29348730
TI - Black ginseng activates Akt signaling, thereby enhancing myoblast differentiation
and myotube growth.
AB - Background: Black ginseng (BG) has greatly enhanced pharmacological activities
relative to white or red ginseng. However, the effect and molecular mechanism of
BG on muscle growth has not yet been examined. In this study, we investigated
whether BG could regulate myoblast differentiation and myotube hypertrophy.
Methods: BG-treated C2C12 myoblasts were differentiated, followed by
immunoblotting for myogenic regulators, immunostaining for a muscle marker,
myosin heavy chain or immunoprecipitation analysis for myogenic transcription
factors. Results: BG treatment of C2C12 cells resulted in the activation of Akt,
thereby enhancing heterodimerization of MyoD and E proteins, which in turn
promoted muscle-specific gene expression and myoblast differentiation. BG-treated
myoblasts formed larger multinucleated myotubes with increased diameter and
thickness, accompanied by enhanced Akt/mTOR/p70S6K activation. Furthermore, the
BG treatment of human rhabdomyosarcoma cells restored myogenic differentiation.
Conclusion: BG enhances myoblast differentiation and myotube hypertrophy by
activating Akt/mTOR/p70S6k axis. Thus, our study demonstrates that BG has
promising potential to treat or prevent muscle loss related to aging or other
pathological conditions, such as diabetes.
PMID- 29348731
TI - Problems with precaution: the transfusion medicine experience.
AB - The precautionary principle is a dominant paradigm governing risk-based decision
making. Today, there are increasing pressures to re-examine aggressive
precautionary approaches, and to assess how the principle should be applied in
the modern system. In this paper, we examined three key applications of
precautionary approaches in the field of transfusion medicine to provide insight
into the risks and benefits of these approaches. The three case studies examined
were the donor deferral policies to safeguard against transfusion transmission of
human immunodeficiency virus, variant Creutzfeldt-Jacob disease, and, lastly,
xenotropic murine leukemia virus-related virus. Characterization of precautionary
applications was conducted using an embedded case study design. Our findings
indicate that transfusion transmission mitigation strategies have become
increasingly aggressive in the face of theoretical risks. In contrast, the review
processes for implementation and reversal of precautionary policies have been
slow, and historical donor deferral policies are still in place today.
Application of precautionary approaches has proved challenging with both benefits
and pitfalls. In light of emerging threats to the blood system, policy-makers
should consider the implementation of frameworks to guide the appropriate
application of precaution in transfusion medicine in the future.
PMID- 29348732
TI - A Flexible System for Cultivation of Methanococcus and Other Formate-Utilizing
Methanogens.
AB - Many hydrogenotrophic methanogens use either H2 or formate as the major electron
donor to reduce CO2 for methane production. The conventional cultivation of these
organisms uses H2 and CO2 as the substrate with frequent replenishment of gas
during growth. H2 is explosive and requires an expensive gassing system to handle
safely. Formate is as an ideal alternative substrate from the standpoints of both
economy and safety but leads to large changes in the culture pH during growth.
Here, we report that glycylglycine is an inexpensive and nontoxic buffer suitable
for growth of Methanococcus maripaludis and Methanothermococcus okinawensis. This
cultivation system is suitable for growth on liquid as well as solid medium in
serum bottles. Moreover, it allows cultivation of liter scale cultures without
expensive fermentation equipment. This formate cultivation system provides an
inexpensive and flexible alternative for the growth of formate-utilizing,
hydrogenotrophic methanogens.
PMID- 29348733
TI - Monte Carlo calculation of photo-neutron dose produced by circular cones at 18 MV
photon beams.
AB - Aim: The aim of this study is to calculate neutron contamination at the presence
of circular cones irradiating by 18 MV photons using Monte Carlo code.
Background: Small photon fields are one of the most useful methods in
radiotherapy. One of the techniques for shaping small photon beams is applying
circular cones made of lead. Using this method in high energy photon due to
neutron contamination is a crucial issue. Materials and methods: Initially,
Varian linac producing 18 MV photons was simulated and after validating the code,
various circular cones were also simulated. Then, the number of neutrons, neutron
equivalent dose and absorbed dose per Gy of photon dose were calculated along the
central axis. Results: Number of neutrons per Gy of photon dose had their maximum
value at depth of 2 cm and these values for 5, 10, 15, 20 and 30 mm circular
cones were 9.02, 7.76, 7.61, 6.02 and 5.08 (n cm-2 Gy-1), respectively. Neutron
equivalent doses per Gy of photon dose had their maximum at the surface of the
phantom and these values for mentioned collimators were 1.48, 1.33, 1.31, 1.12
and 1.08 (mSv Gy-1), respectively. Neutron absorbed doses had their maximum at
the surface of the phantom and these values for mentioned collimators sizes were
103.74, 99.71, 95.77, 81.46 and 78.20 (MUGy/Gy), respectively. Conclusions: As
the field size gets smaller, number of neutrons, equivalent and absorbed dose per
Gy of photon increase. Also, neutron equivalent dose and absorbed dose are
maximum at the surface of phantom and then these values will be decreased.
PMID- 29348735
TI - Dosimetric evaluation of image based brachytherapy using tandem ovoid and tandem
ring applicators.
AB - Aim: The aim of the study is to evaluate the differences in dosimetry between
tandem-ovoid and tandem-ring gynaecologic brachytherapy applicators in image
based brachytherapy. Background: Traditionally, tandem ovoid applicators were
used to deliver dose to tumor in intracavitary brachytherapy. Tandem-ring, tandem
cylinder and hybrid intracavitary, interstitial applicators are also used
nowadays in cervical cancer brachytherapy. Methods and materials: 100 CT datasets
of cervical cancer patients (stage IB2 - IIIB) receiving HDR application (50
tandem-ovoid and 50 tandem-ring) were studied. Brachytherapy was delivered using
a CT-MRI compatible tandem-ovoid (50 patients) and a tandem-ring applicator (50
patients). DVHs were calculated and D2cc was recorded for the bladder and rectum
and compared with the corresponding ICRU point doses. The point B dose, the
treated volume, high dose volume and the treatment time were recorded and
compared for the two applicators. Results: The mean D2cc of the bladder with TR
applicator was 6.746 Gy. TO applicator delivered a mean D2cc of 7.160 Gy to the
bladder. The mean ICRU bladder points were 5.60 and 5.63 Gy for TR and TO
applicator, respectively. The mean D2cc of the rectum was 4.04 Gy and 4.79 Gy for
TR and TO applicators, respectively. The corresponding ICRU point doses were 5.10
Gy and 5.66 Gy, respectively. Conclusions: The results indicate that the OAR
doses assessed by DVH criteria were higher than ICRU point doses for the bladder
with both tandem-ovoid and tandem-ring applicators whereas DVH based dose was
lower than ICRU dose for the rectum. The point B dose, the treated volume and
high dose volume was found to be slightly higher with the tandem-ovoid
applicator. The mean D2cc dose for the bladder and rectum was lower with tandem
ring applicators. The clinical implication of the above dosimetric differences
needs to be evaluated further.
PMID- 29348734
TI - Energy spectrum and dose enhancement due to the depth of the Lipiodol position
using flattened and unflattened beams.
AB - Aim: Lipiodol was used for stereotactic body radiotherapy combining trans
arterial chemoembolization. Lipiodol used for tumour seeking in trans arterial
chemoembolization remains in stereotactic body radiation therapy. In our previous
study, we reported the dose enhancement effect in Lipiodol with 10* flattening
filter-free (FFF). The objective of our study was to evaluate the dose
enhancement and energy spectrum of photons and electrons due to the Lipiodol
depth with flattened (FF) and FFF beams. Methods: FF and FFF for 6 MV beams from
TrueBeam were used in this study. The Lipiodol (3 * 3 * 3 cm3) was located at
depths of 1, 3, 5, 10, 20, and 30 cm in water. The dose enhancement factor (DEF)
and the energy fluence were obtained by Monte Carlo calculations of the particle
and heavy ion transport code system (PHITS). Results: The DEFs at the centre of
Lipiodol with the FF beam were 6.8, 7.3, 7.6, 7.2, 6.1, and 5.7% and those with
the FFF beam were 20.6, 22.0, 21.9, 20.0, 12.3, and 12.1% at depths of 1, 3, 5,
10, 20, and 30 cm, respectively, where Lipiodol was located in water. Moreover,
spectrum results showed that more low-energy photons and electrons were present
at shallow depth where Lipiodol was located in water. The variation in the low
energy spectrum due to the depth of the Lipiodol position was more explicit with
the FFF beam than that with the FF beam. Conclusions: The current study revealed
variations in the DEF and energy spectrum due to the depth of the Lipiodol
position with the FF and FFF beams. Although the FF beam could reduce the effect
of energy dependence due to the depth of the Lipiodol position, the dose
enhancement was overall small. To cause a large dose enhancement, the FFF beam
with the distance of the patient surface to Lipiodol within 10 cm should be used.
PMID- 29348736
TI - Reducing Public Health Risk During Disasters: Identifying Social Vulnerabilities.
AB - All regions of the US experience disasters which result in a number of negative
public health consequences. Some populations have higher levels of social
vulnerability and, thus, are more likely to experience negative impacts of
disasters including emotional distress, loss of property, illness, and death. To
mitigate the impact of disasters on at-risk populations, emergency managers must
be aware of the social vulnerabilities within their community. This paper
describes a qualitative study which aimed to understand how emergency managers
identify social vulnerabilities, also referred to as at-risk populations, in
their populations and barriers and facilitators to current approaches. Findings
suggest that although public health tools have been developed to aid emergency
managers in identifying at-risk populations, they are not being used
consistently. Emergency managers requested more information on the availability
of tools as well as guidance on how to increase ability to identify at-risk
populations.
PMID- 29348738
TI - Key Parameters on the Microwave Assisted Synthesis of Magnetic Nanoparticles for
MRI Contrast Agents.
AB - Uniform iron oxide magnetic nanoparticles have been synthesized using a microwave
assisted synthesis method in organic media and their colloidal, magnetic, and
relaxometric properties have been analyzed after its transference to water and
compared with those nanoparticles prepared by thermal decomposition in organic
media. The novelty of this synthesis relies on the use of a solid iron oleate as
precursor, which assures the reproducibility and scalability of the synthesis,
and the microwave heating that resulted in being faster and more efficient than
traditional heating methods, and therefore it has a great potential for
nanoparticle industrial production. The effect of different experimental
conditions such as the solvent, precursor, and surfactant concentration and
reaction time as well as the transference to water is analyzed and optimized to
obtain magnetic iron oxide nanoparticles with sizes between 8 and 15 nm and
finally colloids suitable for their use as contrast agents on Magnetic Resonance
Imaging (MRI). The r2 relaxivity values normalized to the square of the
saturation magnetization were shown to be constant and independent of the
particle size, which means that the saturation magnetization is the main
parameter controlling the efficiency of these magnetic nanoparticles as MRI T2
contrast agents.
PMID- 29348739
TI - Identification of Sensory Processing and Integration Symptom Clusters: A
Preliminary Study.
AB - Rationale: This study explored subtypes of sensory processing disorder (SPD) by
examining the clinical presentations of cluster groups that emerged from scores
of children with SPD on the Sensory Processing 3-Dimension (SP-3D) Inventory.
Method: A nonexperimental design was used involving data extraction from the
records of 252 children with SPD. Exploratory cluster analyses were conducted
with scores from the SP-3D Inventory which measures sensory overresponsivity
(SOR), sensory underresponsivity (SUR), sensory craving (SC), postural disorder,
dyspraxia, and sensory discrimination. Scores related to adaptive behavior,
social-emotional functioning, and attention among children with different sensory
modulation patterns were then examined and compared. Results: Three distinct
cluster groups emerged from the data: High SOR only, High SUR with SOR, and High
SC with SOR. All groups showed low performance within multiple domains of
adaptive behavior. Atypical behaviors associated with social-emotional
functioning and attention varied among the groups. Implications: The SP-3D
Inventory shows promise as a tool for assisting in identifying patterns of
sensory dysfunction and for guiding intervention. Better characterization can
guide intervention precision and facilitate homogenous samples for research.
PMID- 29348740
TI - GA-Based Membrane Evolutionary Algorithm for Ensemble Clustering.
AB - Ensemble clustering can improve the generalization ability of a single clustering
algorithm and generate a more robust clustering result by integrating multiple
base clusterings, so it becomes the focus of current clustering research.
Ensemble clustering aims at finding a consensus partition which agrees as much as
possible with base clusterings. Genetic algorithm is a highly parallel,
stochastic, and adaptive search algorithm developed from the natural selection
and evolutionary mechanism of biology. In this paper, an improved genetic
algorithm is designed by improving the coding of chromosome. A new membrane
evolutionary algorithm is constructed by using genetic mechanisms as evolution
rules and combines with the communication mechanism of cell-like P system. The
proposed algorithm is used to optimize the base clusterings and find the optimal
chromosome as the final ensemble clustering result. The global optimization
ability of the genetic algorithm and the rapid convergence of the membrane system
make membrane evolutionary algorithm perform better than several state-of-the-art
techniques on six real-world UCI data sets.
PMID- 29348737
TI - In Vivo PET Imaging of Adenosine 2A Receptors in Neuroinflammatory and
Neurodegenerative Disease.
AB - Adenosine receptors are G-protein coupled P1 purinergic receptors that are
broadly expressed in the peripheral immune system, vasculature, and the central
nervous system (CNS). Within the immune system, adenosine 2A (A2A) receptor
mediated signaling exerts a suppressive effect on ongoing inflammation. In
healthy CNS, A2A receptors are expressed mainly within the neurons of the basal
ganglia. Alterations in A2A receptor function and expression have been noted in
movement disorders, and in Parkinson's disease pharmacological A2A receptor
antagonism leads to diminished motor symptoms. Although A2A receptors are
expressed only at a low level in the healthy CNS outside striatum, pathological
challenge or inflammation has been shown to lead to upregulation of A2A receptors
in extrastriatal CNS tissue, and this has been successfully quantitated using in
vivo positron emission tomography (PET) imaging and A2A receptor-binding
radioligands. Several radioligands for PET imaging of A2A receptors have been
developed in recent years, and A2A receptor-targeting PET imaging may thus
provide a potential additional tool to evaluate various aspects of
neuroinflammation in vivo. This review article provides a brief overview of A2A
receptors in healthy brain and in a selection of most important neurological
diseases and describes the recent advances in A2A receptor-targeting PET imaging
studies.
PMID- 29348741
TI - AMOBH: Adaptive Multiobjective Black Hole Algorithm.
AB - This paper proposes a new multiobjective evolutionary algorithm based on the
black hole algorithm with a new individual density assessment (cell density),
called "adaptive multiobjective black hole algorithm" (AMOBH). Cell density has
the characteristics of low computational complexity and maintains a good balance
of convergence and diversity of the Pareto front. The framework of AMOBH can be
divided into three steps. Firstly, the Pareto front is mapped to a new objective
space called parallel cell coordinate system. Then, to adjust the evolutionary
strategies adaptively, Shannon entropy is employed to estimate the evolution
status. At last, the cell density is combined with a dominance strength
assessment called cell dominance to evaluate the fitness of solutions. Compared
with the state-of-the-art methods SPEA-II, PESA-II, NSGA-II, and MOEA/D,
experimental results show that AMOBH has a good performance in terms of
convergence rate, population diversity, population convergence, subpopulation
obtention of different Pareto regions, and time complexity to the latter in most
cases.
PMID- 29348742
TI - Emerging Trends in Machine Learning for Signal Processing.
PMID- 29348743
TI - Fusion Methods for Biosignal Analysis: Theory and Applications.
PMID- 29348744
TI - Improving EEG-Based Motor Imagery Classification for Real-Time Applications Using
the QSA Method.
AB - We present an improvement to the quaternion-based signal analysis (QSA) technique
to extract electroencephalography (EEG) signal features with a view to developing
real-time applications, particularly in motor imagery (IM) cognitive processes.
The proposed methodology (iQSA, improved QSA) extracts features such as the
average, variance, homogeneity, and contrast of EEG signals related to motor
imagery in a more efficient manner (i.e., by reducing the number of samples
needed to classify the signal and improving the classification percentage)
compared to the original QSA technique. Specifically, we can sample the signal in
variable time periods (from 0.5 s to 3 s, in half-a-second intervals) to
determine the relationship between the number of samples and their effectiveness
in classifying signals. In addition, to strengthen the classification process a
number of boosting-technique-based decision trees were implemented. The results
show an 82.30% accuracy rate for 0.5 s samples and 73.16% for 3 s samples. This
is a significant improvement compared to the original QSA technique that offered
results from 33.31% to 40.82% without sampling window and from 33.44% to 41.07%
with sampling window, respectively. We can thus conclude that iQSA is better
suited to develop real-time applications.
PMID- 29348745
TI - Onychomycosis Caused by Fusarium spp. in Dakar, Senegal: Epidemiological,
Clinical, and Mycological Study.
AB - Fusarium spp. represent 9 to 44% of onychomycoses caused by fungi other than
dermatophytes. This retrospective study describes 17 cases of Fusarium
onychomycosis diagnosed at the Laboratory of Parasitology and Mycology of Le
Dantec University Hospital in Dakar, Senegal, from 2014 to 2016. It included all
patients received in the laboratory for suspicion of onychomycosis between
January 1, 2014, and December 31, 2016. Diagnosis was based on mycological
examination including direct examination and culture. Mycological analysis was
considered positive when direct examination and culture were positive after at
least one repeat. Seventeen Fusarium onychomycosis cases representing 12.9% of
all onychomycoses reported were diagnosed. There were 5 cases on the fingernails
and 12 on the toenails in 6 males and 11 females, and the mean age was 44 years
(range: 26-64). Onychomycoses were diagnosed in immunocompetent patients except
in a diabetic patient. The mean duration of lesions was 4.9 years (range: 1-15),
and distal subungual onychomycosis was predominant. Almost all patients were from
suburban areas of Dakar region. The most frequent species isolated belong to
Fusarium solani complex. Because of the risk of disseminated infection in
immunocompromised patients, realization of susceptibility tests is necessary to
ensure better therapeutic management.
PMID- 29348747
TI - Vitamin D Deficiency Is Associated with Endoscopic Severity in Patients with
Crohn's Disease.
AB - Background and Aims: Vitamin D deficiency is common in patients with Crohn's
disease and is associated with disease activity. Relationship between vitamin D
and endoscopic disease activity is unknown. The aim of the study is to determine
the association between vitamin D status and endoscopic disease activity in CD
patients. Methods: Consecutive hospitalized CD patients from 2014 to 2016 who
received vitamin D assessment and colonoscopy were retrospectively evaluated.
Clinical disease activity was assessed by Crohn's disease activity index and C
reactive protein. Endoscopic activity was calculated using simple endoscopic
score for Crohn's disease. Results: Median serum 25OHD level of 131 patients was
lower than healthy controls [21.1 nmol/L (11.8-32.3) versus 49.9 nmol/L (44.9
57.4), P = 0.007]. 125 (95%) patients had vitamin D deficiency and the rest (5%)
had vitamin D insufficiency. Serum 25OHD was inversely correlated with CRP (r =
0.308, P < 0.001), CDAI (r = -0.582, P < 0.001), SES-CD (r = -0.294, P = 0.001),
and endoscopic severity stratified by SES-CD (P = 0.001). Conclusion: Vitamin D
deficiency was prevalent among hospitalized CD patients. Vitamin D levels were
inversely correlated with endoscopic disease activity. Vitamin D status could be
a biomarker in assessing disease activity among hospitalized CD patients in
addition to CDAI and CRP.
PMID- 29348746
TI - Impact of Time-Restricted Feeding and Dawn-to-Sunset Fasting on Circadian Rhythm,
Obesity, Metabolic Syndrome, and Nonalcoholic Fatty Liver Disease.
AB - Obesity now affects millions of people and places them at risk of developing
metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), and even
hepatocellular carcinoma. This rapidly emerging epidemic has led to a search for
cost-effective methods to prevent the metabolic syndrome and NAFLD as well as the
progression of NAFLD to cirrhosis and hepatocellular carcinoma. In murine models,
time-restricted feeding resets the hepatic circadian clock and enhances
transcription of key metabolic regulators of glucose and lipid homeostasis.
Studies of the effect of dawn-to-sunset Ramadan fasting, which is akin to time
restricted feeding model, have also identified significant improvement in body
mass index, serum lipid profiles, and oxidative stress parameters. Based on the
findings of studies conducted on human subjects, dawn-to-sunset fasting has the
potential to be a cost-effective intervention for obesity, metabolic syndrome,
and NAFLD.
PMID- 29348748
TI - Comment on "Differences in Ventilatory Threshold for Exercise Prescription in
Outpatient Diabetic and Sarcopenic Obese Subjects".
PMID- 29348749
TI - The Effect of Number of Teeth and Chewing Ability on Cognitive Function of
Elderly in UAE: A Pilot Study.
AB - Cognitive decline is one of the major causes of disability among the aging
population. The aim of this study was to explore the relationship between oral
health parameters (number of teeth, chewing ability, and presence of a denture)
and cognitive function in the elderly across the UAE. Fifty persons (age >= 60;
71.26 +/- 10.23) were enrolled in the study. Cognitive status was assessed using
the standardized mini-mental state examination (SMMSE) and accordingly,
cognitively normal subjects scoring >=24 were considered as the control group and
cognitively impaired individuals scoring <=23 were considered as the low scoring
group. Chewing ability was examined, number of teeth was noted, and demographical
data was collected. The results of this pilot study showed that individuals with
low SMMSE scores were significantly less educated (P < 0.01) and had fewer number
of remaining teeth (P < 0.05) and impaired chewing ability (P < 0.05). These
results demonstrate a significant link between the number of teeth, chewing
ability, and cognitive function. However, this pilot study had its limitations
and was the first of its kind in the UAE and Gulf region; therefore, future
research addressing the limitations is needed to further explore this
association.
PMID- 29348750
TI - Recent Studies on the Speciation and Determination of Mercury in Different
Environmental Matrices Using Various Analytical Techniques.
AB - This paper reviews the current research on the speciation and determination of
mercury by various analytical techniques, including the atomic absorption
spectrometry (AAS), voltammetry, inductively coupled plasma optical emission
spectrometry (ICP-OES), ICP-mass spectrometry (MS), atomic fluorescence
spectrometry (AFS), spectrophotometry, spectrofluorometry, and high performance
liquid chromatography (HPLC). Approximately 96 research papers on the speciation
and determination of mercury by various analytical instruments published in
international journals since 2015 were reviewed. All analytical parameters,
including the limits of detection, linearity range, quality assurance and
control, applicability, and interfering ions, evaluated in the reviewed articles
were tabulated. In this review, we found a lack of information in speciation
studies of mercury in recent years. Another important conclusion from this review
was that there were few studies regarding the concentration of mercury in the
atmosphere.
PMID- 29348751
TI - Alkaloids Profiling of Fumaria capreolata by Analytical Platforms Based on the
Hyphenation of Gas Chromatography and Liquid Chromatography with Quadrupole-Time
of-Flight Mass Spectrometry.
AB - Two analytical platforms, gas chromatography (GC) coupled to quadrupole-time-of
flight (QTOF) mass spectrometry (MS) and reversed-phase ultrahigh performance
liquid chromatography (UHPLC) coupled to diode array (DAD) and QTOF detection,
were applied in order to study the alkaloid profile of Fumaria capreolata. The
use of these mass analyzers enabled tentatively identifying the alkaloids by
matching their accurate mass signals and suggested molecular formulae with those
previously reported in libraries and databases. Moreover, the proposed structures
were corroborated by studying their fragmentation pattern obtained by both
platforms. In this way, 8 and 26 isoquinoline alkaloids were characterized using
GC-QTOF-MS and RP-UHPLC-DAD-QTOF-MS, respectively, and they belonged to the
following subclasses: protoberberine, protopine, aporphine, benzophenanthridine,
spirobenzylisoquinoline, morphinandienone, and benzylisoquinoline. Moreover, the
latter analytical method was selected to determine at 280 nm the concentration of
protopine (9.6 +/- 0.7 mg/g), a potential active compound of the extract. In
conclusion, although GC-MS has been commonly used for the analysis of this type
of phytochemicals, RP-UHPLC-DAD-QTOF-MS provided essential complementary
information. This analytical method can be applied for the quality control of
phytopharmaceuticals containing Fumaria extracts currently found in the market.
PMID- 29348752
TI - Infrared Drying as a Quick Preparation Method for Dried Tangerine Peel.
AB - To establish the most convenient and effective method to dry tangerine peels,
different methods (sun drying, hot-air drying, freeze drying, vacuum drying, and
medium- and short-wave infrared drying) were exploited. Our results indicated
that medium- and short-wave infrared drying was the best method to preserve
nutraceutical components; for example, vitamin C was raised to 6.77 mg/g (D.W.)
from 3.39 mg/g (sun drying). Moreover, the drying time can be shortened above 96%
compared with sun drying. Importantly, the efficiency of DPPH radical scavenging
was enhanced from 26.66% to 55.92%. These findings would provide a reliable and
time-saving methodology to produce high-quality dried tangerine peels.
PMID- 29348753
TI - Potential Effect of Leukocyte-Platelet-Rich Fibrin in Bone Healing of Skull Base:
A Pilot Study.
AB - Background: Reconstruction of surgical defects following cranial base surgery is
challenging. Others have demonstrated that leukocyte-platelet-rich fibrin (L-PRF)
stimulates tissue healing and bone regeneration. However, these studies have
addressed mostly maxillofacial surgical wounds. Objective: The objective of this
study was to assess the possible adjuvant role of L-PRF in inducing
neoossification of the surgical bone defect in anterior skull base surgery.
Methods: We identified patients who had undergone an endoscopic endonasal surgery
of the anterior skull base in which L-PRF membranes were used for the
reconstruction of the bone defect and who were followed up with postoperative CT
scans. CT findings were then correlated with baseline scans and with the CT scans
of a patient who had undergone imaging and histologic analysis after
maxillofacial surgery in which L-PRF was used and in which we demonstrated bone
formation. Results: Five patients fulfilled the inclusion criteria. In four
patients, the CT scan demonstrated closure of the bony defect by neoosteogenesis;
however, the bone appeared less dense than the surrounding normal bone. A
comparison with the control patient yielded similar radiological features.
Conclusion: This case series suggests that L-PRF may induce bone healing and
regeneration at the surgical site defect. Multi-institutional studies with a
larger series of patients are required to confirm this possibility.
PMID- 29348754
TI - The Impact of Different Classification Criteria Sets on the Estimated Prevalence
and Associated Risk Factors of Diastolic Dysfunction in Rheumatoid Arthritis.
AB - This study compared the estimated prevalence and potential determinants of left
ventricular (LV) diastolic dysfunction upon applying different classification
criteria in rheumatoid arthritis (RA). LV diastolic function was assessed
echocardiographically by pulsed Doppler (E/A), tissue Doppler (E/e', lateral and
septal e'), and left atrial volume index in 176 RA patients. Relationships of
traditional cardiovascular risk factors and RA characteristics with LV diastolic
function and dysfunction according to previous and current criteria were
determined in multivariate regression models. Waist-hip ratio was associated with
E/A (standardised beta (SE) = -0.28 +/- 0.09, p = 0.0002) and lateral e'
(standardised beta (SE) = 0.26 +/- 0.09, p = 0.01); low diastolic blood pressure
was related to E/e' (standardised beta (SE) = -0.16 +/- 0.08, p = 0.04).
Diastolic dysfunction prevalence differed upon applying previous (59%) compared
to current (22%) criteria (p < 0.0001). One SD increase in waist-hip ratio was
associated with diastolic dysfunction when applying current criteria (OR = 2.61
(95% CI = 1.51-4.52), p = 0.0006), whereas one SD increase in diastolic blood
pressure was inversely related to diastolic dysfunction upon using previous
criteria (OR = 0.57 (95% CI = 0.40-0.81), p = 0.002). In conclusion, application
of current and previous diastolic dysfunction criteria markedly alters the
prevalence and risk factors associated with diastolic dysfunction in RA.
PMID- 29348755
TI - Incidentally Discovered Extranodal Marginal Zone B-Cell Lymphoma of Mucosa
Associated Lymphoid Tissue in the Colon.
AB - We present a case of colonic mucosa-associated lymphoid tissue (MALT) lymphoma in
a 62-year-old woman diagnosed after a positive test for fecal occult blood.
PMID- 29348756
TI - Neurolysis for Treatment of Infraorbital Neuropathy.
AB - Two patients, a woman aged 34 and a man aged 56, were included in the study. They
reported the existence of pain in the areas of the infraorbital nerve, which,
over the last four to five years, aggravated by the stimuli of eating, laughing,
and being touched. 2 ml of 0.5% lidocaine was administered to these patients six
times percutaneously. It was observed that the ease of pain lasted until the
local anesthesia lost its effect, and the pain resumed its original intensity.
Neurolysis with 0.5 ml of 50% ethanol was applied to the infraorbital nerve. This
procedure was applied to the first patient twice and three times to the second.
Thereafter, the patients were cured completely. For the treatment of idiopathic
chronic infraorbital neuropathy, the neurolysis of the infraorbital nerve using
50% ethanol could be considered as an effective treatment alternative.
PMID- 29348757
TI - Corrigendum to "Subdural Empyema Complicating Bacterial Meningitis: A Challenging
Diagnosis in a Patient with Polysubstance Abuse".
AB - [This corrects the article DOI: 10.1155/2015/931819.].
PMID- 29348759
TI - The Flavonoid Glabridin Induces OCT4 to Enhance Osteogenetic Potential in
Mesenchymal Stem Cells.
AB - Mesenchymal stem cells (MSCs) are a promising tool for studying intractable
diseases. Unfortunately, MSCs can easily undergo cellular senescence during in
vitro expansion by losing stemness. The aim of this study was to improve the
stemness and differentiation of MSCs by using glabridin, a natural flavonoid.
Assessments of cell viability, cell proliferation, beta-galactosidase activity,
differentiation, and gene expression by reverse transcription PCR were
subsequently performed in the absence or presence of glabridin. Glabridin
enhanced the self-renewal capacity of MSCs, as indicated by the upregulation of
the OCT4 gene. In addition, it resulted in an increase in the osteogenic
differentiation potential by inducing the expression of osteogenesis-related
genes such as DLX5 and RUNX2. We confirmed that glabridin improved the
osteogenesis of MSCs with a significant elevation in the expression of
OSTEOCALCIN and OSTEOPONTIN genes. Taken together, these results suggest that
glabridin enhances osteogenic differentiation of MSCs with induction of the OCT4
gene; thus, glabridin could be useful for stem cell-based therapies.
PMID- 29348760
TI - The Effects of BMP-2, miR-31, miR-106a, and miR-148a on Osteogenic
Differentiation of MSCs Derived from Amnion in Comparison with MSCs Derived from
the Bone Marrow.
AB - Mesenchymal stromal cells (MSCs) offering valuable anticipations for the
treatment of degenerative diseases. They can be found in many tissues including
amnion. MSCs from amnion (AM-MSCs) can differentiate into osteoblast similar to
that of bone marrow-derived MSCs (BM-MSCs). However, the ability is not much
efficient compared to BM-MSCs. This study aimed to examine the effects of BMP-2
and miRNAs on osteogenic differentiation of AM-MSCs compared to those of BM-MSCs.
The osteogenic differentiation capacity after miRNA treatment was assessed by ALP
expression, ALP activity, and osteogenic marker gene expression. The results
showed that the osteogenic differentiation capacity increased after BMP-2
treatment both in AM-MSCs and BM-MSCs. MiR-31, miR-106a, and miR-148a were
downregulated during the osteogenic differentiation. After transfection with anti
miRNAs, ALP activity and osteogenic genes were increased over the time of
differentiation. The data lead to the potential for using AM-MSCs as an
alternative source for bone regeneration. Moreover, the information of miRNA
expression and function during osteogenic differentiation may be useful for the
development of new therapeutics or enhanced an in vitro culture technique
required for stem cell-based therapies in the bone regeneration.
PMID- 29348761
TI - Prevalence of Middle Ear Infections and Associated Risk Factors in Children under
5 Years in Gasabo District of Kigali City, Rwanda.
AB - Middle ear infections are common in children, and delay in diagnosis and
treatment may result in complications such as delays in speech and language
development and deafness. The aim of this study was to determine the prevalence
and care seeking behaviour for middle ear infections in children under five years
in Kigali city. We conducted a cross-sectional study among 810 children aged 6-59
months in Gasabo district of Kigali city, Rwanda. The prevalence of middle ear
infections was 5.8%, of whom 4% had chronic suppurative otitis media. A child was
less likely to develop middle ear infections if they lived in an urban setting
(OR = 0.52, 95% CI: 0.285-0.958) but more likely to develop middle ear infections
if exposed to household smoke (OR = 2.54, 95% CI: 1.18-5.46). Parents were
unlikely to know that their child had an ear infection (OR: 0.15, 95% CI: 0.06
0.34). Middle ear infection remains a public health problem in Rwanda but many
parents were not aware of its presence in the affected children. There is a need
to raise awareness of parents about ear infection and to promote early care
seeking from qualified health workers.
PMID- 29348758
TI - Lymphocytes in Placental Tissues: Immune Regulation and Translational
Possibilities for Immunotherapy.
AB - Immune modulation at the fetomaternal interface is crucial to ensure that the
fetal allograft is not rejected. In the present review, the focus is to describe
basic functions of lymphocyte populations and how they may contribute to
fetomaternal immune regulation, as well as determining what proportions and
effector functions of these cells are reported to be present in placental tissues
in humans. Also explored is the possibility that unique cell populations at the
fetomaternal interface may be targets for adoptive cell therapy. Increasing the
understanding of immune modulation during pregnancy can give valuable insight
into other established fields such as allogeneic hematopoietic stem cell
transplantation and solid organ transplantation. In these settings, lymphocytes
are key components that contribute to inflammation and rejection of either
patient or donor tissues following transplantation. In contrast, an allogeneic
fetus eludes rejection by the maternal immune system.
PMID- 29348762
TI - Kerosene Oil Poisoning among Children in Rural Sri Lanka.
AB - Introduction: Kerosene oil poisoning is one of common presentations to emergency
departments among children in rural territories of developing countries. This
study aimed to describe clinical manifestations, reasons for delayed
presentations, harmful first aid practices, complications, and risk factors
related to kerosene oil poisoning among children in rural Sri Lanka. Methods:
This multicenter study was conducted in North-Central province of Sri Lanka
involving all in-patient children with acute kerosene oil poisoning. Data were
collected over seven years from thirty-six hospitals in the province. Data
collection was done by pretested, multistructured questionnaires and a
qualitative study. Results: Male children accounted for 189 (60.4%) while 283
(93%) children were below five years. The majority of parents belonged to farming
community. Most children ingested kerosene oil in home kitchen. Mortality rate
was 0.3%. Lack of transport facilities and financial resources were common
reasons for delayed management. Hospital transfer rate was 65.5%. Thirty percent
of caregivers practiced harmful first aid measures. Commonest complication was
chemical pneumonitis. Strongest risk factors for kerosene oil poisoning were
unsafe storage, inadequate supervision, and inadequate house space. Conclusions:
Effect of safe storage and community education in reducing the burden of kerosene
oil poisoning should be evaluated. Since many risk factors interact to bring
about the event of poisoning in a child, holistic approaches to community
education in rural settings are recommended.
PMID- 29348764
TI - Study on the Clinical Safe and Effective Methods of Arsenic-Containing Compound
Qinghuang Powder in the Treatment of Myelodysplastic Syndrome.
AB - Objective: To establish the clinical safe and effective methods of arsenic
containing compound-Qinghuang Powder (compound-QHP) in the treatment of
myelodysplastic syndrome (MDS). Methods: 200 patients with MDS were treated with
compound-QHP (daily dose of 0.1 g realgar). The blood arsenic concentrations
(BACs) were detected by atomic fluorescence spectrophotometry (HF-AFS). After
treatment for 1 month, the patients were randomly divided into group A and group
B when the BACs were less than 20 MUg/L. Daily dose of realgar was maintained in
group A and it was increased to that when the BACs were more than 20 MUg/L in
group B. The BAC and clinical efficacy and safety in two groups were compared at
the end of the treatment with compound-QHP. Results: The average BAC of group B
was significantly higher than that of group A (P < 0.01). The rates of hematology
improvement and reduced transfusion were significantly higher in group B than in
group A (P < 0.05). The HGB, ANC, and PLT significantly increased in group B
after treatment (P > 0.05). Conclusions: Monitoring the BAC and adjusting the
daily dose of realgar to increase the effective BAC and then improving efficacy
without increasing the clinical toxicity are the clinical safe and effective
methods in the treatment of MDS.
PMID- 29348763
TI - Inflammasomes in Mycobacterium tuberculosis-Driven Immunity.
AB - The development of effective innate and subsequent adaptive host immune responses
is highly dependent on the production of proinflammatory cytokines that increase
the activity of immune cells. The key role in this process is played by
inflammasomes, multimeric protein complexes serving as a platform for caspase-1,
an enzyme responsible for proteolytic cleavage of IL-1beta and IL-18 precursors.
Inflammasome activation, which triggers the multifaceted activity of these two
proinflammatory cytokines, is a prerequisite for developing an efficient
inflammatory response against pathogenic Mycobacterium tuberculosis (M.tb). This
review focuses on the role of NLRP3 and AIM2 inflammasomes in M.tb-driven
immunity.
PMID- 29348765
TI - Preventive Effect and Safety of a Follicle Stimulating Hormone Inhibitory
Formulation Containing a Mixture of Coicis Semen and Artemisia capillaris for
Precocious Puberty: A Preliminary Experimental Study Using Female Rats.
AB - Background: Precocious puberty is a common endocrine disease in children.
Inappropriate activation of hypothalamic-pituitary-gonadal axis leads to the
development of secondary sexual characteristics at an earlier age than normal
children and causes short stature in adulthood. Objectives: The aim of this study
is to evaluate the preventive effects of a herbal formulation containing a
mixture of Coicis Semen and Artemisia capillaris (hEIF extract) on precocious
puberty. Methods: The preventive effect of hEIF extract on precocious puberty in
rats was evaluated by measuring blood component after 3 weeks of treatment via
oral administration. Network pharmacological analyses were performed to predict
the bioactive components of hEIF extract. Results: In vivo studies showed that
hEIF extract significantly reduced follicle stimulating hormone (FSH) levels.
After treatment with 200 mg/kg of hEIF extract, the FSH level was 5.33 +/- 1.10
ng/mL, whereas the FSH level in the vehicle group was 46.73 +/- 0.80 ng/mL.
Moreover, the use of hEIF extract did not stimulate body growth and bone
accretion in rats. The network pharmacological analysis led to the identification
of multiple targets of hEIF extract related to lipolysis and the female sex
hormone-related pathways. Conclusion: hEIF extract can be used as an FSH
inhibitor for the treatment of precocious puberty.
PMID- 29348766
TI - Inhibition of Tumor Growth of Human Hepatocellular Carcinoma HepG2 Cells in a
Nude Mouse Xenograft Model by the Total Flavonoids from Arachniodes exilis.
AB - A tumor growth model of human hepatocellular carcinoma HepG2 cells in nude mice
was employed to investigate the antitumor activity of the total flavonoids
extracted from Arachniodes exilis (TFAE) in vivo. Several biochemical assays
including hematoxylin-eosin (HE) staining, immunohistochemistry, and Western blot
were performed to elucidate the mechanism of action of total flavonoids extracted
from Arachniodes exilis (TFAE). The results showed that TFAE effectively
inhibited the tumor growth of hepatocellular carcinoma in nude mice and had no
significant effect on body weight, blood system, and functions of liver and
kidney. Expression levels of proapoptotic proteins Bax and cleaved caspase-3
remarkably increased while the expressions of Bcl-2, HIF-1alpha, and VEGF were
suppressed by TFAE. These results suggested that the antitumor potential of TFEA
was implied by the apoptosis of tumor cells and the inhibition of angiogenesis in
tumor tissue.
PMID- 29348767
TI - Dangguijihwang-tang and Dangguijakyak-san Prevent Menopausal Symptoms and
Dangguijihwang-tang Prevents Articular Cartilage Deterioration in Ovariectomized
Obese Rats with Monoiodoacetate-Induced Osteoarthritis.
AB - We investigated whether dangguijakyak-san (DJY) and dangguijihwang-tang (DJH),
oriental medicines traditionally used for inflammatory diseases, could prevent
and/or delay the progression of postmenopausal symptoms and osteoarthritis in
osteoarthritis-induced estrogen-deficient rats. Treated ovariectomized (OVX) rats
consumed either 1% DJY or 1% DJH in the diets. Positive-control rats were given
30 MUg/kg bw 17beta-estradiol and control rats were given 1% fat as were the
normal-control rats. All rats received high-fat diets for 8 weeks. At the 9th
week, OVX rats received articular injections of monoiodoacetate (MIA) or saline
(normal control) into the right knee. At 3 weeks after MIA injection, DJY reduced
visceral-fat mass and improved glucose metabolism by reducing insulin resistance,
whereas DJH increased BMD and decreased insulin resistance. DJH improved weight
distribution in the right knee and maximum running velocity on a treadmill at
days 14 and 21 as much as those of the positive control. TNF-alpha, IL-1beta, and
IL-6 levels in articular cartilage were much higher in the control than the
positive control, whereas both DJY and DJH reduced the levels to those of the
positive control. The histological analysis assessed articular cartilage damage
near the tidemark and proteoglycan loss in the control versus the positive
control; DJY and DJH prevented this damage and proteoglycan loss. In conclusion,
DJY may provide an effective treatment for improving glucose tolerance, and DJH
may be appropriate for preventing osteoarthritis.
PMID- 29348768
TI - Investigating the Mechanisms of Action of Depside Salt from Salvia miltiorrhiza
Using Bioinformatic Analysis.
AB - Salvia miltiorrhiza is a traditional Chinese medicinal herb used for treating
cardiovascular diseases. Depside salt from S. miltiorrhiza (DSSM) contains the
following active components: magnesium lithospermate B, lithospermic acid, and
rosmarinic acid. This study aimed to reveal the mechanisms of action of DSSM.
After searching for DSSM-associated genes in GeneCards, Search Tool for
Interacting Chemicals, SuperTarget, PubChem, and Comparative Toxicogenomics
Database, they were subjected to enrichment analysis using Multifaceted Analysis
Tool for Human Transcriptome. A protein-protein interaction (PPI) network was
visualised; module analysis was conducted using the Cytoscape software. Finally,
a transcriptional regulatory network was constructed using the TRRUST database
and Cytoscape. Seventy-three DSSM-associated genes were identified. JUN, TNF,
NFKB1, and FOS were hub nodes in the PPI network. Modules 1 and 2 were identified
from the PPI network, with pathway enrichment analysis, showing that the presence
of NFKB1 and BCL2 in module 1 was indicative of a particular association with the
NF-kappaB signalling pathway. JUN, TNF, NFKB1, FOS, and BCL2 exhibited notable
interactions among themselves in the PPI network. Several regulatory
relationships (such as JUN -> TNF/FOS, FOS -> NFKB1 and NFKB1 -> BCL2/TNF) were
also found in the regulatory network. Thus, DSSM exerts effects against
cardiovascular diseases by targeting JUN, TNF, NFKB1, FOS, and BCL2.
PMID- 29348769
TI - Research and Development of Atractylodes lancea (Thunb) DC. as a Promising
Candidate for Cholangiocarcinoma Chemotherapeutics.
AB - Treatment and control of cholangiocarcinoma (CCA): the bile duct cancer is
limited by the lack of effective chemotherapeutic drugs and alternative drugs are
needed, particularly those from natural sources. This article reviews steps of
research and development of Atractylodes lancea (Thunb) DC. (AL) as potential
candidate for CCA chemotherapy, with adoption of the reverse pharmacology
approach. Major steps include (1) reviewing of existing information on its
phytochemistry and pharmacological properties, (2) screening of its activities
against CCA, (3) standardization of AL, (4) nonclinical studies to evaluate anti
CCA activities, (5) phytochemistry and standardization of AL extract, (6)
development of oral pharmaceutical formulation of standardized AL extract, and
(7) toxicity testing of oral pharmaceutical formulation of standardized AL
extract. Results from a series of our study confirm anti-CCA potential and safety
profiles of both the crude extract and the finished product (oral pharmaceutical
formulation of the standardized AL extract). Phases I and II clinical trials of
the product to confirm tolerability and efficacy in healthy subjects and patients
with advanced stage CCA will be carried out soon.
PMID- 29348770
TI - Vitamin E-Mediated Modulation of Glutamate Receptor Expression in an Oxidative
Stress Model of Neural Cells Derived from Embryonic Stem Cell Cultures.
AB - Glutamate is the primary excitatory neurotransmitter in the central nervous
system. Excessive concentrations of glutamate in the brain can be excitotoxic and
cause oxidative stress, which is associated with Alzheimer's disease. In the
present study, the effects of vitamin E in the form of tocotrienol-rich fraction
(TRF) and alpha-tocopherol (alpha-TCP) in modulating the glutamate receptor and
neuron injury markers in an in vitro model of oxidative stress in neural-derived
embryonic stem (ES) cell cultures were elucidated. A transgenic mouse ES cell
line (46C) was differentiated into a neural lineage in vitro via induction with
retinoic acid. These cells were then subjected to oxidative stress with a
significantly high concentration of glutamate. Measurement of reactive oxygen
species (ROS) was performed after inducing glutamate excitotoxicity, and recovery
from this toxicity in response to vitamin E was determined. The gene expression
levels of glutamate receptors and neuron-specific enolase were elucidated using
real-time PCR. The results reveal that neural cells derived from 46C cells and
subjected to oxidative stress exhibit downregulation of NMDA, kainate receptor,
and NSE after posttreatment with different concentrations of TRF and alpha-TCP, a
sign of neurorecovery. Treatment of either TRF or alpha-TCP reduced the levels of
ROS in neural cells subjected to glutamate-induced oxidative stress; these
results indicated that vitamin E is a potent antioxidant.
PMID- 29348771
TI - A Review on the Medicinal Plant Dalbergia odorifera Species: Phytochemistry and
Biological Activity.
AB - The crucial medicinal plant Dalbergia odorifera T. Chen species belongs to genus
Dalbergia, with interesting secondary metabolites, consisting of main classes of
flavonoid, phenol, and sesquiterpene derivatives, as well as several
arylbenzofurans, quinones, and fatty acids. Biological studies were carried out
on extracts, fractions, and compounds from this species involved in cytotoxic
assays; antibacterial, antioxidative, anti-inflammatory, antithrombotic,
antiplatelet, antiosteosarcoma, antiosteoporosis, antiangiogenesis, and
prostaglandin biosynthetic enzyme inhibition activities; vasorelaxant activities;
alpha-glucosidase inhibitory activities; and many other effects. In terms of the
valuable resources for natural new drugs development, D. odorifera species are
widely used as medicinal drugs in many countries for treatment of cardiovascular
diseases, cancer, diabetes, blood disorders, ischemia, swelling, necrosis, or
rheumatic pain. Although natural products from this plant have been increasingly
playing an important role in drug discovery programs, there is no supportive
evidence to provide a general insight into phytochemical studies on D. odorifera
species and biological activities of extracts, fractions, and isolated compounds.
To a certain extent, this review deals with an overview of almost naturally
occurring compounds from this species, along with extensive coverage of their
biological evaluations.
PMID- 29348772
TI - Kyungheechunggan-Tang-01, a New Herbal Medication, Suppresses LPS-Induced
Inflammatory Responses through JAK/STAT Signaling Pathway in RAW 264.7
Macrophages.
AB - Medicinal plants have been used as alternative therapeutic tools to alleviate
inflammatory diseases. The objective of this study was to evaluate anti
inflammatory properties of Kyungheechunggan-tang- (KCT-) 01, KCT-02, and
Injinchunggan-tang (IJCGT) as newly developed decoctions containing 3-11 herbs in
LPS-induced macrophages. KCT-01 showed the most potent inhibitory effects on LPS
induced NO, PGE2, TNF-alpha, and IL-6 production among those three herbal
formulas. In addition, KCT-01 significantly inhibited LPS-induced iNOS and COX-2
at protein levels and expression of iNOS, COX-2, TNF-alpha, and IL-6 at mRNA
levels. Molecular data revealed that KCT-01 attenuated the activation of JAK/STAT
signaling cascade without affecting NF-kappaB or AP-1 activation. In ear
inflammation induced by croton oil, KCT-01 significantly reduced edema, MPO
activity, expression levels of iNOS and COX-2, and STAT3 phosphorylation in ear
tissues. Taken together, our findings suggest that KCT-01 can downregulate the
expression of proinflammatory genes by inhibiting JAK/STAT signaling pathway
under inflammatory conditions. This study provides useful data for further
exploration and application of KCT-01 as a potential anti-inflammatory medicine.
PMID- 29348773
TI - Poly-epsilon-Caprolactone Microsphere Polymers Containing Usnic Acid: Acute
Toxicity and Anti-Inflammatory Activity.
AB - Usnic acid (UA) has been studied by its pharmacological properties; however, it
presents moderate toxicity, low solubility, and absorption by biological
membranes. The aim of this study was to develop poly-epsilon-caprolactone
microsphere polymers containing UA (UA-micro) and evaluate their acute toxicity
and anti-inflammatory activity. The microspheres were prepared by multiple
emulsion technique (water/oil/water) and characterized by the encapsulation
efficiency, particle size, polydispersity index, and zeta potential. The acute
toxicity of UA and UA-micro (25-50 mg/kg; p.o.) was evaluated in mice. The anti
inflammatory activity of UA and UA-micro was evaluated by subcutaneous air pouch
and carrageenan-induced paw edema in rat, with measurement of inflammatory
cytokines and MPO levels. The UA presented encapsulation efficiency of 97.72%,
particle size of 13.54 micrometers, polydispersity index of 2.36, and zeta
potential of 44.5 +/- 2.95 mV. The UA-micro presented lower acute toxicity (LD50
value up to 2000 mg/kg; p.o.) when compared to UA. UA-micro and UA (25 mg/kg)
significantly reduced paw volume and decreased MPO levels, whereas only UA-micro
(50 mg/kg) reduced significantly IL-1beta, TNF-alpha, and NO levels in
inflammatory exudate. These results suggest that controlled release systems, as
microspheres, can be a promising alternative to reduce the toxicity of UA, making
it a viable compound for inflammation therapy.
PMID- 29348774
TI - Five Indigenous Plants of Pakistan with Antinociceptive, Anti-Inflammatory,
Antidepressant, and Anticoagulant Properties in Sprague Dawley Rats.
AB - Five medicinal plants of Pakistan were investigated for their antinociceptive,
anti-inflammatory, antidepressant, and anticoagulant potential. Antinociceptive
activity was estimated by hot plate and writhing assay. In hot plate assay,
Quercus dilatata (52.2%) and Hedera nepalensis (59.1%) showed moderate while
Withania coagulans (65.3%) displayed a significant reduction in pain. On the
other hand, in writhing assay, Quercus dilatata (49.6%), Hedera nepalensis
(52.7%), and Withania coagulans (62.0%) showed comparative less activity. In anti
inflammatory assays crude extracts showed significant edema inhibition in a dose
dependent manner. In carrageenan assay, the highest activity was observed for
Withania coagulans (70.0%) followed by Quercus dilatata (66.7%) and Hedera
nepalensis (63.3%). Similar behavior was observed in histamine assay with
percentage inhibitions of 74.3%, 60.4%, and 63.5%, respectively. Antidepressant
activity was estimated by forced swim test and the most potent activity was
revealed by Withania coagulans with immobility time 2.2s (95.9%) followed by
Hedera nepalensis with immobility time 25.3s (53.4%). Moreover, the crude
extracts of Fagonia cretica (74.6%), Hedera nepalensis (73.8%), and Phytolacca
latbenia (67.3%) showed good anticoagulant activity with coagulation times 86.9s,
84.3s, and 67.5s, respectively. Collectively, the results demonstrate that these
five plants have rich medicinal constituents which can be further explored.
PMID- 29348775
TI - Testicular Dysfunction Ameliorative Effect of the Methanolic Roots Extracts of
Maytenus procumbens and Ozoroa paniculosa.
AB - The traditional use of medicinal plants in the management of sexual dysfunctions
has a long history. This study investigated testicular dysfunction ameliorative
effect of the methanolic roots extracts of Maytenus procumbens and Ozoroa
paniculosa in a butanol-induced testicular dysfunction rat model. The rats in
respective experimental groups were orally administered with the extract at 50
and 250 mg/kg bw, daily for 28 days. The cytotoxicity of the extracts was
evaluated against HEK293, MCF-7, and HT29 cell lines. The extracts exhibited
moderate (LC50 30.3-330.2 MUg/mL) to weak (LC50 200.8-438.4 MUg/mL) cytotoxicity
level on the cancer and normal cells, respectively. While relatively lower serum
testosterone levels and total sperm count along with decreased numbers of
spermatogonia were noted in the untreated group, all these parameters were
improved in the groups treated with the extracts at 250 mg/kg. Improved
histomorphological changes of the testes were also observed when compared to the
untreated group. While the extracts (at 250 mg/kg) increased serum reduced
glutathione content and decreased malondialdehyde content, a relatively higher
serum creatinine level was also observed in the treated animals group. The
results indicate that the two plant extracts have potential to ameliorate
testicular dysfunction.
PMID- 29348776
TI - Effects of the Fruit Extract of Tribulus terrestris on Skin Inflammation in Mice
with Oxazolone-Induced Atopic Dermatitis through Regulation of Calcium Channels,
Orai-1 and TRPV3, and Mast Cell Activation.
AB - Ethnopharmacological Relevance: In this study, we investigated the effects of
Tribulus terrestris fruit (Leguminosae, Tribuli Fructus, TF) extract on oxazolone
induced atopic dermatitis in mice. Materials and Methods: TF extract was prepared
with 30% ethanol as solvent. The 1% TF extract with or without 0.1% HC was
applied to the back skin daily for 24 days. Results: 1% TF extract with 0.1% HC
improved AD symptoms and reduced TEWL and symptom scores in AD mice. 1% TF
extract with 0.1% HC inhibited skin inflammation through decrease in inflammatory
cells infiltration as well as inhibition of Orai-1 expression in skin tissues. TF
extract inhibited Orai-1 activity in Orai-1-STIM1 cooverexpressing HEK293T cells
but increased TRPV3 activity in TRPV3-overexpressing HEK293T cells. TF extract
decreased beta-hexosaminidase release in RBL-2H3 cells. Conclusions: The present
study demonstrates that the topical application of TF extract improves skin
inflammation in AD mice, and the mechanism for this effect appears to be related
to the modulation of calcium channels and mast cell activation. This outcome
suggests that the combination of TF and steroids could be a more effective and
safe approach for AD treatment.
PMID- 29348777
TI - A Randomized Controlled Study of the Yi Qi Gu Biao Pill in the Treatment of
Frequent Exacerbator Phenotype in Chronic Obstructive Pulmonary Disease (Lung and
Spleen Qi Deficiency Syndrome).
AB - Objective: To evaluate the efficacy and safety of Yi Qi Gu Biao (YQGB) pill in
treating frequent exacerbator phenotype in chronic obstructive pulmonary disease
(lung and spleen qi deficiency syndrome) (FEPCOPD). Methods: This prospective,
randomized, double-blind, controlled study assessed 112 cases (64 included) of
FEPCOPD treated at the outpatient department in our hospital in January-August
2016. The patients were randomly divided into YQGB and placebo (Pb) and treated
for three months. Lung function, CAT, mMRC, and TCM symptom scores (TCMs) were
observed. Results: Compared with Pb, YQGB showed decreased wheezing symptom
scores (WSs) and TCMs at one month and decreased CAT and TCMs at three months.
From one to three months, CAT, cough, sputum, WSs, and TCMs in YQGB were lower
than pretreatment values. But in Pb, CAT was lower than pretreatment values after
one month; CAT, sputum, and TCMs were lower than pretreatment values after two
months; CAT, cough, sputum, WSs, and TCMs were lower than pretreatment values
after three months. Conclusion: Yi Qi Gu Biao pill can improve wheezing, health
status, and TCMs in FEPCOPD and also can shorten the durations of cough, sputum,
and wheezing. This trial is registered in the Clinical Trials Registry of China:
ChiCTR-IOR-15007542 (on 8 December 2015).
PMID- 29348778
TI - Marketing health education: advertising margarine and visualising health in
Britain from 1964-c.2000.
AB - During the post-war period, margarine was re-conceptualised as a value-added
product with distinct health benefits. This article contextualises the
advertising of margarine as a healthy food, focusing on Unilever's Flora brand as
an important case study in legitimising the emergent role of disease prevention
as a marketing tool. It uses the methodology of visual culture to examine how
advertising employed chronic disease prevention as a selling tool. This article
assesses how the post-war environment gave rise to new ways of visually
advertising food, and how these promoted innovative visualisations of food, the
body and their interactions with health.
PMID- 29348779
TI - Mutual proximity graphs for improved reachability in music recommendation.
AB - This paper is concerned with the impact of hubness, a general problem of machine
learning in high-dimensional spaces, on a real-world music recommendation system
based on visualisation of a k-nearest neighbour (knn) graph. Due to a problem of
measuring distances in high dimensions, hub objects are recommended over and over
again while anti-hubs are nonexistent in recommendation lists, resulting in poor
reachability of the music catalogue. We present mutual proximity graphs, which
are an alternative to knn and mutual knn graphs, and are able to avoid hub
vertices having abnormally high connectivity. We show that mutual proximity
graphs yield much better graph connectivity resulting in improved reachability
compared to knn graphs, mutual knn graphs and mutual knn graphs enhanced with
minimum spanning trees, while simultaneously reducing the negative effects of
hubness.
PMID- 29348781
TI - Sequential Probability Ratio Testing with Power Projective Base Method Improves
Decision-Making for BCI.
AB - Obtaining a fast and reliable decision is an important issue in brain-computer
interfaces (BCI), particularly in practical real-time applications such as
wheelchair or neuroprosthetic control. In this study, the EEG signals were
firstly analyzed with a power projective base method. Then we were applied a
decision-making model, the sequential probability ratio testing (SPRT), for
single-trial classification of motor imagery movement events. The unique strength
of this proposed classification method lies in its accumulative process, which
increases the discriminative power as more and more evidence is observed over
time. The properties of the method were illustrated on thirteen subjects'
recordings from three datasets. Results showed that our proposed power projective
method outperformed two benchmark methods for every subject. Moreover, with
sequential classifier, the accuracies across subjects were significantly higher
than that with nonsequential ones. The average maximum accuracy of the SPRT
method was 84.1%, as compared with 82.3% accuracy for the sequential Bayesian
(SB) method. The proposed SPRT method provides an explicit relationship between
stopping time, thresholds, and error, which is important for balancing the time
accuracy trade-off. These results suggest SPRT would be useful in speeding up
decision-making while trading off errors in BCI.
PMID- 29348782
TI - Adsorption and Desulfurization Mechanism of Thiophene on Layered FeS(001), (011),
and (111) Surfaces: A Dispersion-Corrected Density Functional Theory Study.
AB - Layered transition-metal chalcogenides have emerged as a fascinating new class of
materials for catalysis. Here, we present periodic density functional theory
(DFT) calculations of the adsorption of thiophene and the direct desulfurization
reaction pathways on the (001), (011), and (111) surfaces of layered FeS. The
fundamental aspects of the thiophene adsorption, including the initial adsorption
geometries, adsorption energies, structural parameters, and electronic
properties, are presented. From the calculated adsorption energies, we show that
the flat adsorption geometries, wherein the thiophene molecule forms multiple pi
bonds with the FeS surfaces, are energetically more favorable than the upright
adsorption geometries, with the strength of adsorption decreasing in the order
FeS(111) > FeS(011) > FeS(001). The adsorption of the thiophene onto the reactive
(011) and (111) surfaces is shown to be characterized by charge transfer from the
interacting Fe d-band to the pi-system of the thiophene molecule, which causes
changes of the intramolecular structure including loss of aromaticity and
elongation of the C-S bonds. The thermodynamic and kinetic analysis of the
elementary steps involved in the direct desulfurization of thiophene on the
reactive FeS surfaces is also presented. Direct desulfurization of thiophene
occurs preferentially on the (111) surface, as reflected by the overall
exothermic reaction energy calculated for the process (ER = -0.15 eV), with an
activation energy of 1.58 eV.
PMID- 29348783
TI - Breast Massage, Implant Displacement, and Prevention of Capsular Contracture
After Breast Augmentation With Implants: A Review of the Literature.
AB - Objective: Capsular contracture, the most common complication following breast
augmentation with implants, is a complex inflammatory reaction that ultimately
leads to fibrosis at the contact site between the implant and tissue. A number of
peri-, pre-, and postoperative techniques have been postulated and implemented by
many surgeons to reduce the incidence of capsular contracture. Breast massage and
implant displacement technique is a commonly recommended practice that has not
been well studied in regard to capsular contracture prevention. The authors
present a review of the literature addressing methods and efficacy of massage and
implant displacement techniques after breast augmentation. Methods: A literature
review was performed using PubMed and the Cochrane Collaboration Library for
primary research articles on breast massage or implant displacement after breast
augmentation with implants for breast contracture prevention between January 1975
and March 2017. Exclusion criteria were studies that were focused on the
treatment rather than prevention of breast contracture, addressed other
strategies of preventing contracture as the main focus, or did not report the
number of patients studied. Information related to massage technique and capsular
contracture outcomes was extracted. Results: The literature search yielded 4
relevant studies, with a total of 587 patients. Outcomes evaluated included
massage technique, onset of massage, frequency of massage, and incidence of
capsular contracture. Breast massage was introduced between 2 days and 2 weeks
postoperatively, performed twice daily, and lasted from 2 to 5 minutes for each
breast. Final postoperative follow-up concluded between 6 and 36 months. The
average capsular contracture rate was similar, 31% (range, 0-35) in the massage
group versus 40% (range, 30-90) in the nonmassage group. Conclusions: While
multiple techniques have been proposed and practiced in the prevention of
capsular contracture, breast massage and implant displacement techniques remain
controversial. While there is a method to measure adequacy of breast massage
pressure, it is not widely utilized. The available data do not support breast
massage to prevent capsular contracture; more studies with standardized
techniques are needed to better assess the efficacy of breast massage in
preventing capsular contracture.
PMID- 29348780
TI - Host factors that influence mother-to-child transmission of HIV-1: genetics,
coinfections, behavior and nutrition.
AB - Mother-to-child transmission (MTCT) is the most important mode of HIV-1
acquisition among infants and children and it can occur in utero, intrapartum and
postnatally through breastfeeding. Great progress has been made in preventing
MTCT through use of antiretroviral regimens during gestation, labor/delivery and
breastfeeding. The mechanisms of MTCT, however, are multifactorial and remain
incompletely understood. This review focuses on select host factors affecting
MTCT, in particular genetic factors, coexisting infections, behavioral factors
and nutrition. Whereas much emphasis has been placed on decreasing maternal HIV-1
viral load, an important determinant of MTCT, through use of antiretroviral
agents, complementary focus on overall maternal health is often neglected. By
addressing coinfections in mothers and infants, improving the mother's
nutritional status and modifying risky behaviors and practices, not only is
maternal and child health improved, but a direct benefit in reducing MTCT can be
derived. The study of genetic variations in susceptibility to HIV-1 infection is
rapidly evolving, and the future is likely to bring revolutionary changes in HIV
1 prevention by enhancing natural resistance to infection and by individually
tailoring pharmacologic regimens.
PMID- 29348784
TI - Recipient Vessel Selection in Head and Neck Reconstruction.
AB - Objective: Recipient vessel caliber may be the single most important variable for
flow to free tissue transfer. We performed cadaveric dissection of the external
carotid artery and its branches to analyze average diameter in order to determine
an algorithm for recipient vessel selection in head and neck reconstruction.
Methods: The external carotid artery and branches were exposed on 3 lightly
embalmed male human cadavers, aged 82 to 85 years. Each vessel was dissected, and
luminal diameters were recorded with calipers. Results: The proximal ECA had the
greatest average diameter (4 +/- 0.6 mm) and potential flow; followed by distal
ECA (2.85 +/- 0.4 mm) facial (2.0 +/- 0.6 mm), lingual (1.65 +/- 0.6 mm),
superior thyroid (1 +/- 0.3 mm), and superficial temporal (0.85 +/- 0.4 mm).
There was a trend towards size variation between sides of the same cadaver.
Conclusion: The external carotid artery has the greatest internal diameter and
potential blood flow. It should be considered, when feasible, especially for
defects of the upper third of the head. For defects of the lower third, the
facial artery and the lingual artery should be utilized before the smaller
diameter superior thyroid artery. Vessel selection is more challenging in the
setting of radiation therapy, complex trauma, and prior neck surgery. In these
settings, it is useful to have knowledge of the vascular anatomy and an objective
algorithm for recipient vessel selection.
PMID- 29348785
TI - New Insights into the Benefits of Polyphenols in Chronic Diseases.
PMID- 29348787
TI - Oxidative Stress in Metabolic Disorders and Drug-Induced Injury: The Potential
Role of Nrf2 and PPARs Activators.
PMID- 29348786
TI - DNA Methylation and the Potential Role of Methyl-Containing Nutrients in
Cardiovascular Diseases.
AB - Patients suffering from cardiovascular diseases (CVDs) experience a low quality
of life and increase pressure on healthcare systems both nationally and globally.
DNA methylation, which refers to the pathway by which DNA methyltransferase
facilitates the addition of a methyl group to DNA, is of critical importance in
this respect primarily because the epigenetic modification is implicated in a
range of serious conditions including atherosclerosis, CVDs, and cancer. Research
findings indicate that the number of epigenetic alterations can be elicited (both
in utero and in adults) through the administration of certain nutritional
supplements, including folic acid and methionine; this is partly attributable to
the effect employed by methyl-containing nutrients in DNA methylation. Thus, for
the purpose of illuminating viable therapeutic measures and preventive strategies
for CVDs, research should continue to explore the intricate associations that
exist between epigenetic regulation and CVD pathogenesis. This review centers on
an exposition of the mechanism by which DNA methylation takes place, the impact
it has on a range of conditions, and the potential clinical value of nutrition,
driven mainly by the observation that nutritional supplements such as folic acid
can affect DNA methylation.
PMID- 29348788
TI - The Role of Redox-Regulating Enzymes in Inoperable Breast Cancers Treated with
Neoadjuvant Chemotherapy.
AB - Although validated predictive factors for breast cancer chemoresistance are
scarce, there is emerging evidence that the induction of certain redox-regulating
enzymes may contribute to a poor chemotherapy effect. We investigated the
possible association between chemoresistance and cellular redox state regulation
in patients undergoing neoadjuvant chemotherapy (NACT) for breast cancer. In
total, 53 women with primarily inoperable or inflammatory breast cancer who were
treated with NACT were included in the study. Pre-NACT core needle biopsies and
postoperative tumor samples were immunohistochemically stained for nuclear factor
erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1),
thioredoxin (Trx), and peroxiredoxin I (Prx I). The expression of all studied
markers increased during NACT. Higher pre-NACT nuclear Prx I expression predicted
smaller size of a resected tumor (p = 0.00052; r = -0.550), and higher pre-NACT
cytoplasmic Prx I expression predicted a lower amount of evacuated nodal
metastasis (p = 0.0024; r = -0.472). Pre-NACT nuclear Trx expression and pre-NACT
nuclear Keap1 expression had only a minor prognostic significance as separate
factors, but when they were combined, low expression for both antibodies before
NACT predicted dismal disease-free survival (log-rank p = 0.0030). Our results
suggest that redox-regulating enzymes may serve as potential prognostic factors
in primarily inoperable breast cancer patients.
PMID- 29348789
TI - Pretreatment Donors after Circulatory Death with Simvastatin Alleviates Liver
Ischemia Reperfusion Injury through a KLF2-Dependent Mechanism in Rat.
AB - Objective: Severe hepatic ischemia reperfusion injury (IRI) can result in poor
short- and long-term graft outcome after transplantation. The way to improve the
viability of livers from donors after circulatory death (DCD) is currently
limited. The aim of the present study was to explore the protective effect of
simvastatin on DCD livers and investigate the underlying mechanism. Methods: 24
male rats randomly received simvastatin or its vehicle. 30 min later, rat livers
were exposed to warm ischemia in situ for 30 min. Livers were removed and cold
stored in UW solution for 24 h, subsequently reperfused for 60 min with an
isolated perfused rat liver system. Liver injury was evaluated during and after
warm reperfusion. Results: Pretreatment of DCD donors with simvastatin
significantly decreased IRI liver enzyme release, increased bile output and ATP,
and ameliorated hepatic pathological changes. Simvastatin maintained the
expression of KLF2 and its protective target genes (eNOS, TM, and HO-1), reduced
oxidative stress, inhibited innate immune responses and inflammation, and
increased the expression of Bcl-2/Bax to suppress hepatocyte apoptosis compared
to DCD control group. Conclusion: Pretreatment of DCD donors with simvastatin
improves DCD livers' functional recovery probably through a KLF2-dependent
mechanism. These data suggest that simvastatin may provide a potential benefit
for clinical DCD liver transplantation.
PMID- 29348790
TI - Effects of Aging and Tocotrienol-Rich Fraction Supplementation on Brain Arginine
Metabolism in Rats.
AB - Accumulating evidence suggests that altered arginine metabolism is involved in
the aging and neurodegenerative processes. This study sought to determine the
effects of age and vitamin E supplementation in the form of tocotrienol-rich
fraction (TRF) on brain arginine metabolism. Male Wistar rats at ages of 3 and 21
months were supplemented with TRF orally for 3 months prior to the dissection of
tissue from five brain regions. The tissue concentrations of L-arginine and its
nine downstream metabolites were quantified using high-performance liquid
chromatography and liquid chromatography tandem mass spectrometry. We found age
related alterations in L-arginine metabolites in the chemical- and region
specific manners. Moreover, TRF supplementation reversed age-associated changes
in arginine metabolites in the entorhinal cortex and cerebellum. Multiple
regression analysis revealed a number of significant neurochemical-behavioral
correlations, indicating the beneficial effects of TRF supplementation on memory
and motor function.
PMID- 29348791
TI - Zinc Protects Oxidative Stress-Induced RPE Death by Reducing Mitochondrial Damage
and Preventing Lysosome Rupture.
AB - Zinc deficiency is known to increase the risk of the development of age-related
macular degeneration (AMD), although the underlying mechanism remains poorly
defined. In this study, we investigated the effect of zinc on retinal pigment
epithelium (RPE) survival and function under oxidative conditions. Zinc level was
5.4 MUM in normal culture conditions (DMEM/F12 with 10% FCS) and 1.5 MUM in serum
free medium (DMEM/F12). Under serum-free culture conditions, the treatment of RPE
cells with oxidized photoreceptor outer segment (oxPOS) significantly increased
intracellular ROS production, reduced ATP production, and promoted RPE death
compared to oxPOS-treated RPE under normal culture condition. Serum deprivation
also reduced RPE phagocytosis of oxPOS and exacerbated oxidative insult-induced
cathepsin B release from lysosome, an indicator of lysosome rupture. The addition
of zinc in the serum-free culture system dose dependently reduced ROS production,
recovered ATP production, and reduced oxidative stress- (oxPOS- or 4-HNE) induced
cell death. Zinc supplementation also reduced oxidative stress-mediated cathepsin
B release in RPE cells. Our results suggest that zinc deficiency sensitizes RPE
cells to oxidative damage, and zinc supplementation protects RPE cells from
oxidative stress-induced death by improving mitochondrial function and preventing
lysosome rupture.
PMID- 29348792
TI - Coenzyme Q10 Regulates Antioxidative Stress and Autophagy in Acute Myocardial
Ischemia-Reperfusion Injury.
AB - Background: Oxidative stress and autophagy both play key roles in continuous
cardiomyocyte death and cardiac dysfunction after reperfusion therapy for acute
myocardial ischemia-reperfusion injury. Coenzyme Q10 (CQ10), which is a fat
soluble quinone antioxidant, is involved in the pathophysiological processes of
neurodegenerative diseases, cancer, diabetes, heart failure, and other diseases.
Our objective was to determine if, and by what mechanism, CQ10 can ameliorate
acute myocardial ischemia-reperfusion injury and improve heart function. Methods
and Results: Fat-soluble CQ10 in soybean oil solvent was preconditioned in rats
with acute myocardial ischemia-reperfusion injury by intraperitoneal injection.
Oxidant and antioxidant levels were compared between the preconditioned and
control groups. Autophagy was measured by Western blotting analysis of autophagy
proteins. Proapoptotic proteins and immunofluorescence were used to assess cell
apoptosis. Infarct size was determined by triphenyl tetrazolium chloride (TTC)
staining and Evans blue staining and visualized myocardial pathology by tissue
staining. Finally, we assessed cardiac function by electrocardiography (ECG) and
hemodynamics. Conclusions: This study reveals that CQ10 preconditioning regulates
antioxidant levels and the oxidant balance, enhances autophagy, reduces
myocardial apoptosis and death, and improves cardiac function in rats with acute
ischemia-reperfusion injury. These results imply that CQ10 protects against acute
myocardial ischemia-reperfusion injury via the antioxidative stress and autophagy
pathways.
PMID- 29348794
TI - Tubby-like protein 1 (Tulp1) is a target of microRNA-134 and is down-regulated in
experimental epilepsy.
AB - MicroRNAs are important determinants of gene expression via post-transcriptional
control of the protein levels of their mRNA targets. MicroRNA-134 (miR-134) has
emerged as an important brain-specific microRNA which has been implicated in the
control of dendritic spine morphology, neuronal differentiation and apoptosis.
Here we show that Tubby-like protein 1 (Tulp1) is a target of miR-134. Tulp1
protein showed a similar cellular distribution pattern in the hippocampus to miR
134 and displayed an inverse expression pattern in the mouse retina.
Bioinformatics analyses identified a conserved miR-134 binding site in the 3'
untranslated region of both mouse and human Tulp1 and luciferase reporter assays
confirmed miR-134 targets Tulp1 in vitro. Induction of prolonged seizures in mice
resulted in upregulation of miR-134 and downregulation of protein levels of Tulp1
which were reversed in animals injected with locked nucleic acid-modified
antagomirs targeting miR-134. Finally, knockdown of Tulp1 in human neurons caused
an increase in vulnerability to excitotoxicity. These data identify Tulp1/TULP1
as a novel target of miR-134, which may contribute to underlying pathomechanisms
in epilepsy.
PMID- 29348795
TI - Therapeutic angiogenesis of exosomes for ischemic stroke.
AB - Angiogenesis is the process through which new blood vessels are formed, while
therapeutic angiogenesis aims to promote and control the angiogenic response.
Ischemia results from the lack of blood flow with oxygen and nutrients.
Therapeutic angiogenesis is crucial in preserving brain tissue and bodily
functions after ischemic stroke. Various approaches have been proposed to promote
angiogenesis in ischemic diseases. Traditional protein/gene and subsequent
stem/progenitor cell approaches have not shown consistent efficacy for ischemic
diseases in clinical trials. Exosomes are microparticles secreted from cells and
conduct cell-cell communication including stem cell or cancer cell induced pro
angiogenesis. Utilization of exogenous exosomes for the treatment of ischemic
diseases is an emerging approach which may prevent certain disadvantages such as
easy degradation and tumor formation happened in other strategies. This review
highlights recent reports on the use of exosomes as a therapeutic agent to
promote angiogenesis in ischemic stroke.
PMID- 29348793
TI - Inflammasome in drug abuse.
AB - Drug abuse disorders refer to a set of related negative health implications
associated with compulsive drug seeking and use. Because almost all addictive
drugs act on the brain, many of them cause neurological impairments after long
term abuse. Neuropathological studies have revealed a widespread impairment of
the cellular elements. As the key components to limit the damage of neural cells,
CNS immune system is also found affected by these drugs, directly or indirectly.
It has been shown that drugs of abuse alter neuroimmune gene expression and
signaling. Growing studies on neuroimmune factors further demonstrate their
indispensable role in drugs-induced neurotoxicity. As an important
proinflammatory intracellular receptor, inflammasome is activated in many
neurodegenerative diseases in response to a broad range of damage-associated
molecular patterns (DAMPs) signals. In the cases of drug abuse, especially in
those with comorbid of HIV infection and sustained pain, inflammasome activation
significantly promotes the neuroinflammation-associated toxicities. To understand
inflammasome in drug-associated neurotoxic activity, we reviewed the role played
by inflammasome in drug abuse-induced microglial neurotoxicity and evaluated the
potential of imflammasone as a therapeutic target for drug abuse disorders based
on recent development of various selective small-molecular inflammasome
inhibitors.
PMID- 29348796
TI - Condition-specific transcriptional regulation of neuronal ion channel genes in
brain ischemia.
AB - In the context of seeking novel therapeutic targets for treating ischemic stroke,
the preconditioning ischemia-induced brain ischemic tolerance has been used as a
model of endogenously operative, broad-based neuroprotective mechanisms.
Targeting such mechanisms is considered potentially less prone to adverse side
effects, as those seen in many failed clinical trials that focus on single
targets using exogenous compounds. Results from previous studies have revealed an
overall decrease in potassium channel activity in tolerance development. The
objective of this study is to identify ion channel genes that are differentially
regulated under different brain ischemic conditions, as a mean to identify those
ion channels that are associated with ischemic brain injury and ischemic
tolerance. In mice in vivo, transient focal cerebral ischemia was induced by
middle cerebral artery occlusion. In cultured neuronal cells in vitro, simulated
ischemia was modeled by oxygen-glucose deprivation. For both in vivo and in vitro
studies, three principal ischemic conditions were included: ischemic
preconditioned, injured and tolerant, respectively, plus appropriate controls. In
these model systems, transcript levels of a panel of 84 neuronal ion channels
genes were analyzed with a quantitative real-time PCR mini-array. The results
showed that, both in vivo and in vitro, there was a predominant down regulation
in neuronal ion channel genes under ischemic-tolerant conditions, and an up
regulation in ischemic injury. Similar changes were observed among potassium,
sodium and calcium channel genes. A number of regulated genes exhibited opposing
changes under ischemic-injured and ischemic-tolerant conditions. This subset of
ion channel genes exemplifies potentially novel leads for developing multi
factorial therapeutic targets for treating ischemic stroke.
PMID- 29348797
TI - Experimentally-induced ventricular arrhythmias.
AB - Hypoxia and reoxygenation, ischemia and reperfusion, catecholamine infusion,
ouabain, sodium pentobarbital and caffeine, can all be used experimentally to
induce ventricular arrhythmias. According to the Lambeth Convention guidelines
our experimentally-induced ventricular arrhythmias include but are not limited
to: ventricular premature beats (VPB), ventricular salvos (VS), ventricular
bigeminy (VB), nonsustained ventricular tachycardia (VTn), sustained ventricular
tachycardia (VTs) and ventricular fibrillation (VF, or if the heart is not
defibrillated, sudden cardiac death). We have studied these arrhythmias in the
absence and presence of adenosine deaminase, methyl xanthines, and more recently,
acetaminophen. Our laboratory was the first to discover the anti-arrhythmic
properties of acetaminophen an analgesic used in Western medicine for more than
100 years before our publication. We have also identified other cardioprotective
properties of acetaminophen, and have begun to work out some of the
cellular/molecular mechanisms. For example, we know that acetaminophen protects
hypoxic/ischemic cardiac mitochondria, in part, by sustaining function of the
mitochondrial permeability transition pore (MPTP, a protein involved in
regulating mitochondrial pH). Acetaminophen also attenuates the actions of matrix
metalloproteinases that can be harmful to myocardial contractile proteins. Of
course, like all science, more work is needed to expand on these and related
topics.
PMID- 29348798
TI - TRPM7 is a unique target for therapeutic intervention of stroke.
AB - Ischemic stroke is a leading cause of death and long-term disabilities. The
current therapy is limited to thrombolysis and mechanical recanalization, which
have limited success. A better understanding of the mechanisms underlying
ischemic brain injury is therefore needed for the development of more effective
interventions. Glutamate receptor-mediated Ca2+ overload and neurotoxicity have
been well established for decades. However, clinical trials failed to show a
satisfactory effect with the antagonists of glutamate receptors. Other glutamate
independent mechanisms, such as activation of acid-sensing ion channels and
transient receptor potential melastatin 7 (TRPM7), have recently emerged as
important events responsible for neuronal injury under ischemic conditions. In
this review, we discuss how TRPM7 channels participate in ischemic brain injury.
PMID- 29348799
TI - Low-dose ethanol excites lateral habenula neurons projecting to VTA, RMTg, and
raphe.
AB - It is unclear how social drinking can contribute to the development of addiction
in susceptible individuals. However, alcohol's aversive properties are a well
known factor contributing to its abuse. The lateral habenula (LHb) is a key brain
structure responding to various aversive stimuli, including those related to
alcohol. We recently reported that ethanol at 10 mM or less that can be achieved
by social drinking activates many LHb neurons and drives aversive conditioning.
The current study sought to identify LHb circuits that are activated by a low
dose of ethanol using immunohistochemistry and anatomic tracing techniques on
adult Sprague-Dawley rats. We showed here that an intraperitoneal injection of
ethanol (0.25 g/kg), resulting in a blood ethanol concentration of 5.6 mM,
significantly increased the number of cFos immunoreactive (IR) neurons in the
LHb. Most of the ethanol-activated cFos-IR LHb neurons expressed vGluT2
(vesicular glutamate transporters 2, a marker of a glutamatergic phenotype).
These LHb neurons projected to the ventral tegmental area (VTA), rostromedial
tegmental nucleus (RMTg), and dorsal raphe. Moreover, injections of the
anterograde tracer AAV-CaMKIIa-eGFP into the lateral hypothalamus produced a
significant amount of labeled fibers with vGluT2 positive terminals on the
ethanol-activated LHb cells. These results indicate that the LHb neurons
stimulated by a low-dose of ethanol project to the VTA, RMTg, and dorsal raphe,
and receive excitatory projections from the lateral hypothalamus. These
neurocircuits may play a crucial role in mediating the initial aversive effects
produced by a low-dose of ethanol.
PMID- 29348800
TI - Methanolic extract of Cola nitida elicits dose-dependent diuretic, natriuretic
and kaliuretic activities without causing electrolyte impairment, hepatotoxicity
and nephrotoxicity in rats.
AB - Cola nitida (Kolanut) is conventionally used in tropical Africa for the treatment
of all kinds of ailments such as migraine, morning sickness, metabolic disorders
etc. However, this study was designed to investigate the diuretic, natriuretic
and kaliuretic activities of methanolic extract of Cola nitida (MECN) in male
Wistar rats. Adult male Wistar rats were randomly allotted into control (25 ml/kg
b.w.), furosemide (20 mg/kg b.w; standard), MECN1 (100 mg/kg), MECN2 (200 mg/kg),
MECN3 (300 mg/kg), MECN4 (400 mg/kg), MECN5 (500 mg/kg), MECN6 (600 mg/kg) groups
with n=6. The extract was prepared as previously described and the treatment
lasted for 14 days. Urine volume and diuretic indices were estimated. Urine
electrolytes, plasma electrolytes, plasma/renal AST/ALT, plasma creatinine and
urea were assayed using flame photometry and standard colorimetric method
respectively.Administration of different doses of C. nitida significantly altered
body weight gain and water intake but not food intake compared with control
group. There were significant increases in urine volume and urine electrolytes
(Na+, K+ and Cl-), a decrease in plasma/renal ALT and AST activities, a decrease
in plasma creatinine and urea concentration and no alteration in plasma
electrolytes when compared with control and furosemide-treated groups. Our study
suggests that MECN elicits diuretic, natriuretic, and kaliuretic activities
without causing electrolyte impairment, hepatotoxicity and nephrotoxicity. These
effects are dose-dependent.
PMID- 29348801
TI - The Attack of the Smart Particles: Should Bacteria Be Afraid?
AB - A shocking state of affairs; the use of nanoparticles as simple carriers is dead
and outdated. Stimuli-responsive nanoparticles have emerged as active
participants in the therapeutic landscape, rather than inert molecule carriers.
And this time they are here to join the ongoing war against an old enemy:
bacteria.
PMID- 29348802
TI - Fluorescent Carbon Nanoparticles in Medicine for Cancer Therapy: An Update.
AB - In the past few years since our viewpoint on carbon nanoparticles was first
published in 2013 (Kumar, V.; Toffoli, G.; Rizzolio, F. ACS Med. Chem. Lett.2013,
4 (11), 1012-1013), a considerable progress has been made in the area of
synthesis, functionalization, and applications of fluorescent carbon
nanoparticles (CNPs). This update aims to highlight some key points achieved in
the last 4 years in the development of CNPs with a particular emphasis on the
approaches to ameliorate clinical applications of CNPs as therapeutics,
diagnostics, and theranostics agents.
PMID- 29348803
TI - Synthesis of a Chloroalkene Dipeptide Isostere-Containing Peptidomimetic and Its
Biological Application.
AB - The first rapid and efficient chemical synthesis of a cyclic Arg-Gly-Asp (RGD)
peptide containing a chloroalkene dipeptide isostere (CADI) is reported. By a
developed synthetic method, an N-tert-butylsulfonyl protected CADI was obtained
utilizing diastereoselective allylic alkylation as a key reaction. This CADI was
also transformed into an N-Fmoc protected CADI in a few steps. The CADI was used
in Fmoc-based solid-phase peptide synthesis. The first synthesis of a CADI
containing cyclic RGD peptide was successful, and the synthesized CADI-containing
peptidomimetic was found to be a more potent inhibitor against integrin-mediated
cell attachment than the parent cyclic peptide.
PMID- 29348804
TI - Lysine Analogue of Polymyxin B as a Significant Opportunity for Photodynamic
Antimicrobial Chemotherapy.
AB - In order to highlight the potential of photodynamic antimicrobial chemotherapy in
case of infections by antibiotic resistant-strains, a new antimicrobial peptide
conjugate has been synthesized, consisting of a derivative of polymyxin B and a
cationic porphyrin covalently attached together to a spacer. A polymyxin-derived
moiety was subjected to a primary structural modification in the replacement of
four diaminobutyrate residues with lysine ones. This modification was done in
order to strongly reduce bactericidal activity, with the aim to eliminate the
potential rise of polymyxin-resistant strains. Despite this modification, this
new conjugate displayed a strong photobactericidal activity against Gram-positive
as well as Gram-negative bacteria. It was further shown that this conjugate was
able to strongly stick to the cell walls of either kind of strain, thus helping
to inactivate bacteria through the production of reactive oxygen species under
light irradiation.
PMID- 29348805
TI - Synthesis and SAR of 1,2,3,4-Tetrahydroisoquinoline-Based CXCR4 Antagonists.
AB - CXCR4 is the most common chemokine receptor expressed on the surface of many
cancer cell types. In comparison to normal cells, cancer cells overexpress CXCR4,
which correlates with cancer cell metastasis, angiogenesis, and tumor growth.
CXCR4 antagonists can potentially diminish the viability of cancer cells by
interfering with CXCL12-mediated pro-survival signaling and by inhibiting
chemotaxis. Herein, we describe a series of CXCR4 antagonists that are derived
from (S)-5,6,7,8-tetrahydroquinolin-8-amine that has prevailed in the literature.
This series removes the rigidity and chirality of the tetrahydroquinoline
providing 2-(aminomethyl)pyridine analogs, which are more readily accessible and
exhibit improved liver microsomal stability. The medicinal chemistry strategy and
biological properties are described.
PMID- 29348806
TI - Therapeutic Nanosystem Consisting of Singlet-Oxygen-Responsive Prodrug and
Photosensitizer Excited by Two-Photon Light.
AB - Using light as the sole stimulus and employing the generated singlet oxygen as a
therapeutic agent and the trigger to activate chemo-drug release could serve as
an elegant way to bring into full play the advantageous features of light and
enhance therapeutic efficacy through a combination of chemotherapy and
photodynamic therapy. Herein a liposomal drug system has been developed by
embedding a fluorescent photosensitizer and a prodrug into phospholipid vesicles.
Upon one- or two-photon light irradiation, the photosensitizer generates singlet
oxygen, which removes the protecting group of the prodrug and subsequently causes
the release of the active drug chlorambucil. With the combined action of O21 and
chlorambucil, highly controllable cytotoxicity toward cancer cells was achieved.
In addition, the fluorescent photosensitizer gives out fluorescent signal acting
as the drug monitoring agent. This strategy may provide an efficient approach for
cancer treatment and some useful insights for designing light-stimulated on
demand therapeutic systems.
PMID- 29348807
TI - Discovery of Spiro Oxazolidinediones as Selective, Orally Bioavailable Inhibitors
of p300/CBP Histone Acetyltransferases.
AB - p300 and its paralog CBP can acetylate histones and other proteins and have been
implicated in a number of diseases characterized by aberrant gene activation,
such as cancer. A novel, highly selective, orally bioavailable histone
acetyltransferase (HAT) domain inhibitor has been identified through virtual
ligand screening and subsequent optimization of a unique hydantoin screening hit.
Conformational restraint in the form of a spirocyclization followed by
substitution with a urea led to a significant improvement in potency. Replacement
of the hydantoin moiety with an oxazolidinedione followed by fluoro substitution
led to A-485, which exhibits potent cell activity, low clearance, and high oral
bioavailability.
PMID- 29348808
TI - Dual NAMPT/HDAC Inhibitors as a New Strategy for Multitargeting Antitumor Drug
Discovery.
AB - Novel dual nicotinamide phosphoribosyltransferase (NAMPT) and histone deacetylase
(HDAC) inhibitors were designed by a pharmacophore fusion approach. The
thiazolocarboxamide inhibitors were highly active for both targets. In
particular, compound 7f (NAMPT IC50 = 15 nM, HDAC1 IC50 = 2 nM) showed potent in
vivo antitumor efficacy in the HCT116 xenograft model. The study offers a new
strategy for multitarget antitumor drug discovery by simultaneously acting on
cancer metabolism and epigenetics.
PMID- 29348809
TI - Discovery of MK-8722: A Systemic, Direct Pan-Activator of AMP-Activated Protein
Kinase.
AB - 5'-Adenosine monophosphate-activated protein kinase (AMPK) is a key regulator of
mammalian energy homeostasis and has been implicated in mediating many of the
beneficial effects of exercise and weight loss including lipid and glucose
trafficking. As such, the enzyme has long been of interest as a target for the
treatment of Type 2 Diabetes Mellitus. We describe the optimization of beta1
selective, liver-targeted AMPK activators and their evolution into systemic pan
activators capable of acutely lowering glucose in mouse models. Identifying
surrogates for the key acid moiety in early generation compounds proved essential
in improving beta2-activation and in balancing improvements in plasma unbound
fraction while avoiding liver sequestration.
PMID- 29348810
TI - Structure-Based Virtual Screening for the Discovery of Novel Inhibitors of New
Delhi Metallo-beta-lactamase-1.
AB - Bacterial resistance has become a worldwide concern after the emergence of
metallo-beta-lactamases (MBLs). They represent one of the major mechanisms of
bacterial resistance against beta-lactam antibiotics. Among MBLs, New Delhi
metallo-beta-lactamase-1 NDM-1, the most prevalent type, is extremely efficient
in inactivating nearly all-available antibiotics including last resort
carbapenems. No inhibitors for NDM-1 are currently available in therapy, making
the spread of NDM-1 producing bacterial strains a serious menace. With this
perspective, we performed a structure-based in silico screening of a commercially
available library using FLAPdock and identified several, non-beta-lactam
derivatives as promising candidates active against NDM-1. The binding affinities
of the highest scoring hits were measured in vitro revealing, for some of them,
low micromolar affinity toward NDM-1. For the best inhibitors, efficacy against
resistant bacterial strains overexpressing NDM-1 was validated, confirming their
favorable synergistic effect in combination with the carbapenem Meropenem.
PMID- 29348811
TI - Disconnecting the Estrogen Receptor Binding Properties and Antimicrobial
Properties of Parabens through 3,5-Substitution.
AB - Commercially utilized parabens are employed for their antimicrobial properties,
but a weak binding to the estrogen receptor alpha (ERalpha) may lead to breast
cancer in some applications. Modification of the paraben scaffold should allow
for a disconnection of these observed properties. Toward this goal, various 3,5
substituted parabens were synthesized and assessed for antimicrobial properties
against S. aureus as well as competitive binding to the ERalpha. The minimum
inhibitory concentration assay confirmed retention of antimicrobial activity in
many of these derivatives, while all compounds exhibited decreased xenoestrogen
activity as determined by a combination of competitive enzyme linked
immunosorbent assay (ELISA), proliferation, and estrogen receptor binding assay.
Thus, these changes to the paraben scaffold have led to a multitude of paraben
derivatives with antimicrobial properties up to 16 times more active than the
parent paraben and that are devoid or significantly diminished of potential
breast cancer causing properties.
PMID- 29348812
TI - Design and Synthesis of Isoquinolidinobenzodiazepine Dimers, a Novel Class of
Antibody-Drug Conjugate Payload.
AB - Antibody-drug conjugates (ADCs) represent an important class of emerging cancer
therapeutics. Recent ADC development efforts highlighted the use of
pyrrolobenzodiazepine (PBD) dimer payload for the treatment of several cancers.
We identified the isoquinolidinobenzodiazepine (IQB) payload (D211), a new class
of PBD dimer family of DNA damaging payloads. We have successfully synthesized
all three IQB stereoisomers, experimentally showed that the purified (S,S)-D211
isomer is functionally more active than (R,R)-D221 and (S,R)-D231 isomers by
>50,000-fold and ~200-fold, respectively. We also synthesized a linker-payload
(D212) that uses (S,S)-D211 payload with a cathepsin cleavable linker, a
hydrophilic PEG8 spacer, and a thiol reactive maleimide. In addition, homogeneous
ADCs generated using D212 linker-payload exhibited ideal physicochemical
properties, and anti-CD33 ADC displayed a robust target-specific potency on AML
cell lines. These results demonstrate that D212 linker-payload described here can
be utilized for developing novel ADC therapeutics for targeted cancer therapy.
PMID- 29348813
TI - Synthesis and Structure-Activity Relationship Study of Biliatresone, a Plant
Isoflavonoid That Causes Biliary Atresia.
AB - We report the first synthesis of the plant isoflavonoid biliatresone. The
convergent synthesis has been applied to the synthesis of several analogs, which
have facilitated the first structure-activity relationship study for this
environmental toxin that, on ingestion, recapitulates the phenotype of biliary
atresia.
PMID- 29348814
TI - Targeting CD38 alleviates tumor-induced immunosuppression.
PMID- 29348815
TI - Lysosome-targeting agents in cancer therapy.
AB - Despite considerable efforts from multiple laboratories worldwide, highly
specific inhibitors of autophagy for clinical use are not yet available.
Lysosomal inhibitors are being employed instead, in spite of multiple limitations
that are summarized herein.
PMID- 29348816
TI - Development of a predictive miRNA signature for breast cancer risk among high
risk women.
AB - Significant limitations exist in our ability to predict breast cancer risk at the
individual level. Circulating microRNAs (C-miRNAs) have emerged as measurable
biomarkers (liquid biopsies) for cancer detection. We evaluated the ability of C
miRNAs to identify women most likely to develop breast cancer by profiling miRNA
from serum obtained long before diagnosis. 24 breast cancer cases and controls
(matched for risk and age) were identified from women enrolled in the High-Risk
Breast Program at the UVM Cancer Center. Isolated RNA from serum was profiled for
over 2500 human miRNAs. The miRNA expression data were input into a stepwise
linear regression model to discover a multivariable miRNA signature that predicts
long-term risk of breast cancer. 25 candidate miRNAs were identified that
individually classified cases and controls based on statistical methodologies. A
refined 6-miRNA risk-signature was discovered following regression modeling that
distinguishes cases and controls (AUC0.896, CI 0.804-0.988) in this cohort. A
functional relationship between miRNAs that cluster together when cases are
contrasted against controls was suggested and confirmed by pathway analyses. The
discovered 6 miRNA risk-signature can discriminate high-risk women who ultimately
develop breast cancer from those who remain cancer-free, improving current risk
assessment models. Future studies will focus on functional analysis of the miRNAs
in this signature and testing in larger cohorts. We propose that the combined
signature is highly significant for predicting cancer risk, and worthy of further
screening in larger, independent clinical cohorts.
PMID- 29348817
TI - A Mitochondrial-targeted purine-based HSP90 antagonist for leukemia therapy.
AB - Reprogramming of mitochondrial functions sustains tumor growth and may provide
therapeutic opportunities. Here, we targeted the protein folding environment in
mitochondria by coupling a purine-based inhibitor of the molecular chaperone Heat
Shock Protein-90 (Hsp90), PU-H71 to the mitochondrial-targeting moiety,
triphenylphosphonium (TPP). Binding of PU-H71-TPP to ADP-Hsp90, Hsp90 co
chaperone complex or mitochondrial Hsp90 homolog, TRAP1 involved hydrogen bonds,
pi-pi stacking, cation-pi contacts and hydrophobic interactions with the
surrounding amino acids in the active site. PU-H71-TPP selectively accumulated in
mitochondria of tumor cells (17-fold increase in mitochondria/cytosol ratio),
whereas unmodified PU-H71 showed minimal mitochondrial localization. Treatment of
tumor cells with PU-H71-TPP dissipated mitochondrial membrane potential,
inhibited oxidative phosphorylation in sensitive cell types, and reduced ATP
production, resulting in apoptosis and tumor cell killing. Unmodified PU-H71 had
no effect. Bioinformatics analysis identified a "mitochondrial Hsp90" signature
in Acute Myeloid Leukemia (AML), which correlates with worse disease outcome.
Accordingly, inhibition of mitochondrial Hsp90s killed primary and cultured AML
cells, with minimal effects on normal peripheral blood mononuclear cells. These
data demonstrate that directing Hsp90 inhibitors with different chemical
scaffolds to mitochondria is feasible and confers improved anticancer activity. A
potential "addiction" to mitochondrial Hsp90s may provide a new therapeutic
target in AML.
PMID- 29348818
TI - High CYP2E1 activity correlates with hepatofibrogenesis induced by nitrosamines.
AB - Hepatofibrosis, which leads to cirrhosis and eventual hepatocellular carcinoma,
is a common response to chronic toxin-mediated liver injury. Nitrosamines are
potent hepatotoxic agents that cause necrosis and subsequent fibrosis in the
liver as a result of cytochrome P450 2E1 (CYP2E1)-dependent metabolism, which
generates toxic metabolites that form adducts with nucleic acids, leading to
hepatotoxicity and mutagenesis. Herein, CYP2E1 activity and content were
determined in fibrotic liver tissue from patients with hepatocellular carcinoma.
The relationship between CYP2E1 innate activity and hepatofibrogenesis was
evaluated, the effect of inhibition of CYP2E1 activity on hepatofibrosis was
determined in a Sprague-Dawley rat model of diethylnitrosamine-induced
hepatofibrosis. The results demonstrated that the CYP2E1 activities in human
fibrotic tissues are significantly higher than that in normal liver tissues. In
rats treated with diethylnitrosamine, the livers demonstrated various degree of
fibrotic changes and collagen deposition in individual rats. The Ishak score,
which determines the stage of fibrosis, correlated with CYP2E1 innate activity,
with greater fibrosis in rat livers with higher CYP2E1 innate activity.
Inhibition of CYP2E1 during diethylnitrosamine treatment decreased hepatofibrosis
and there was an inverse correlation between the degree of inhibition and the
extent of hepatofibrosis. Therefore, high CYP2E1 activity is a risk factor for
hepatofibrogenesis induced by nitrosamines.
PMID- 29348819
TI - Recombinant protein of Haemonchus contortus small GTPase ADP-ribosylation factor
1 (HcARF1) modulate the cell mediated immune response in vitro.
AB - ADP-ribosylation factors (ARFs) are members of the Ras-related small GTPase
family involved in the vesicular trafficking regulation. Immunomodulatory effects
of these proteinson host cell arenot being addressed yet. H. contortus small
GTPase ADP-ribosylation 1 gene (HcARF1) was cloned and recombinant protein of
HcARF1 (rHcARF1) was successfully expressed in Escherichia coli. Binding activity
of rHcARF1 to goat PBMCs was confirmed by immunofluorescence assay (IFA) and its
immunomudulatory effects on cytokine secretion, cell proliferation, cell
migration and nitric oxide production (NO) were observed by co-incubation of
rHcARF1. IFA results revealed that rHcARF1 could bind to the PBMCs. The
interaction of rHcARF1 modulated the cytokine production, the production of IL-4,
IL-10 and IL-17 was increased in a dose dependent manner, however, the IFN-gamma
production was significantly decreased. Cell migration and NO production were
significantly increased by rHcARF1, whereas, rHcARF1 treatment significantly
suppressed the proliferation of the PBMC in a dose dependent manner. Our findings
showed that the rHcARF1 play important roles on the goat PBMCs.
PMID- 29348820
TI - Effects of different cytokines on immune responses of rainbow trout in a virus
DNA vaccination model.
AB - Seven rainbow trout cytokine genes (interleukin (IL)-2, IL-8, IL-15, IL-17, IL
1beta, intracellular interferon (iIFN) 1a, and IFN-gamma2) were evaluated for
their adjuvant effects on a DNA vaccine, called pG, containing the glycoprotein
gene of infectious hematopoietic necrosis virus (IHNV). Distinct DNA constructs
in expression plasmid pcDNA3.1 encoding a cytokine gene were generated.
Immunofluorescence assays in rainbow trout gonadal cells demonstrated successful
protein expression from all these constructs. Subsequently, fish were immunized
with pG alone or together with a cytokine expression plasmid. Results showed that
each cytokine plasmids at an appropriate dose showed notable effects on immune
gene expression. IL-17 and IFN-gamma2 can enhance early specific IgM response.
All cytokines, except IL-8, can benefit initial neutralizing antibody (NAb)
titers. At 35 days post immunization (dpi), NAb titers of fish immunized with pG
and IL-2, iIFN1a, or IFN-gamma2 plasmids remained at high levels (1:160). NAb
titers of fish immunized with pG alone decreased to 1:40. IL-8 or IL-1beta can
enhance antigen-specific proliferative T-cell responses at 14 dpi. At 28 dpi,
coinjection of pG with IL-2, IL-8, IL-15, or IL-17 plasmids induced considerably
stronger lymphocyte proliferation than that with injection of pG alone. All
cytokine plasmids delivered with pG plasmid enhanced protection of trout against
IHNV-mediated mortality. These results indicate that the type and dose of trout
cytokine genes injected into fish affect quality of immune response to DNA
vaccination.
PMID- 29348821
TI - Glycan microarray reveal induced IgGs repertoire shift against a dietary
carbohydrate in response to rabbit anti-human thymocyte therapy.
AB - Humans have circulating antibodies against diverse glycans containing N
glycolylneuraminic acid (Neu5Gc) due to function-loss mutation of the CMAH gene.
This xenogenic non-human carbohydrate is abundant in red meat, xenografts and
biotherapeutics. Low levels of diet-derived Neu5Gc is also present on normal
human endothelial cells, and together with anti-Neu5Gc antibodies could
potentially mediate "xenosialitis" chronic-inflammation. Rabbit anti-human
thymocyte globulin (ATG) is a drug containing polyclonal IgG glycoproteins
commonly used as an immunosuppressant in human transplantation and autoimmune
diseases. In type-1 diabetes patients, infusion of Neu5Gc-glycosylated ATG caused
increased global anti-Neu5Gc response. Here, for the first time we explore
changes in anti-Neu5Gc IgG repertoire following the immunization elicited by ATG,
compared with the basal antibodies repertoire that reflect exposure to dietary
Neu5Gc. We used glycan microarrays with multiple Neu5Gc-glycans and controls to
elucidate eventual differences in ATG-elicited repertoire, before/after ATG
administration and track their kinetics (0, 1, 18 and 24 months). Response of all
basal-pre-existing Neu5Gc-specific antibodies rapidly increased. This response
peaked at one month post-ATG, with enhanced affinity, then resolved at 18-24
months. Induced-antibodies showed expanded diversity and de-novo recognition of
different Neu5Gc-glycans, including endogenous glycolipids, that was further
validated by affinity-purified anti-Neu5Gc antibodies from patients' sera. These
findings strongly suggest that ATG-induced anti-Neu5Gc IgGs represent a secondary
exposure to this dietary carbohydrate-antigen in humans, with immune memory.
Given their modified recognition patterns, ATG-evoked anti-Neu5Gc antibodies
could potentially mediate biological effects different from pre-existing
antibodies.
PMID- 29348822
TI - The localization of pre mRNA splicing factor PRPF38B is a novel prognostic
biomarker that may predict survival benefit of trastuzumab in patients with
breast cancer overexpressing HER2.
AB - Cancer biomarkers that can define disease status and provide a prognostic insight
are essential for the effective management of patients with breast cancer (BC).
The prevalence, clinicopathological and prognostic significance of PRPF38B
expression in a consecutive series of 1650 patients with primary invasive breast
carcinoma were examined using immunohistochemistry. Furthermore, the
relationship(s) between clinical outcome and PRPF38B expression was explored in
627 patients with ER-negative (oestrogen receptor) disease, and 322 patients with
HER2-overexpressing disease. Membranous expression of PRPF38B was observed in
148/1388 (10.7%) cases and was significantly associated with aggressive
clinicopathological features, including high grade, high mitotic index,
pleomorphism, invasive ductal carcinoma of no specific type (IDC-NST), ER
negative, HER2-overexpression and p53 mutational status (all p < 0.01). In
patients with ER-negative disease receiving chemotherapy, nuclear expression of
PRPF38B was significantly associated with a reduced risk of relapse (p = 0.0004),
whereas membranous PRPF38B expression was significantly associated with increased
risk of relapse (p = 0.004; respectively) at a 5 year follow-up. When patients
were stratified according to ER-negative/HER2-positive status, membranous PRPF38B
expression was associated with a higher risk of relapse in those patients that
did not receive trastuzumab therapy (p = 0.02), whereas in those patients with ER
negative/HER2-positive disease that received trastuzumab adjuvant therapy,
membranous PRPF38B expression associated with a lower risk of relapse (p =
0.00018). Nuclear expression of PRPF38B is a good prognostic indicator in both ER
negative patients and ER-negative/HER2-positive BC (breast cancer) patients,
whereas membranous localisation of PRPF38B is a poor prognostic biomarker that
predicts survival benefit from trastuzumab therapy in patients with ER
negative/HER2-overexpressing BC.
PMID- 29348823
TI - Prevalence of pathogenic germline variants detected by multigene sequencing in
unselected Japanese patients with ovarian cancer.
AB - Pathogenic germline BRCA1, BRCA2 (BRCA1/2), and several other gene variants
predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma
(OC), although variant frequency and relevance information is scarce in Japanese
women with OC. Using targeted panel sequencing, we screened 230 unselected
Japanese women with OC from our hospital-based cohort for pathogenic germline
variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were
identified in 41 (17.8%) women: 19 (8.3%; BRCA1), 8 (3.5%; BRCA2), 6 (2.6%;
mismatch repair genes), 3 (1.3%; RAD51D), 2 (0.9%; ATM), 1 (0.4%; MRE11A), 1
(FANCC), and 1 (GABRA6). Carriers of BRCA1/2 or any other tested gene pathogenic
variants were more likely to be diagnosed younger, have first or second-degree
relatives with OC, and have OC classified as high-grade serous carcinoma (HGSC).
After adjustment for these variables, all 3 features were independent predictive
factors for pathogenic variants in any tested genes whereas only the latter two
remained for variants in BRCA1/2. Our data indicate similar variant prevalence in
Japanese patients with OC and other ethnic groups and suggest that HGSC and OC
family history may facilitate genetic predisposition prediction in Japanese
patients with OC and referring high-risk patients for genetic counseling and
testing.
PMID- 29348824
TI - KCa3.1 channel inhibition leads to an ICAM-1 dependent increase of cell-cell
adhesion between A549 lung cancer and HMEC-1 endothelial cells.
AB - Early metastasis leads to poor prognosis of lung cancer patients, whose 5-year
survival rate is only 15%. We could recently show that the Ca2+ sensitive K+
channel KCa3.1 promotes aggressive behavior of non-small cell lung cancer (NSCLC)
cells and that it can serve as a prognostic marker in NSCLC. Since NSCLC patients
die of metastases, we investigated whether KCa3.1 channels contribute to poor
patient prognosis by regulating distinct steps of the metastatic cascade. We
investigated the extravasation of NSCLC cells and focused on their adhesion to
endothelial cells and on transendothelial migration. We quantified the adhesion
forces between NSCLC cells and endothelial cells by applying single cell force
spectroscopy, and we monitored transendothelial migration using live-cell
imaging. Inhibition of KCa3.1 channels with senicapoc or KCa3.1 silencing
increases the adhesion force of A549 lung cancer cells to human microvascular
endothelial cells (HMEC-1). Western blotting, immunofluorescence staining and
biotinylation assays indicate that the elevated adhesion force is due to
increased expression of ICAM-1 in both cell lines when KCa3.1 channels are
downregulated. Consistent with this interpretation, an anti-ICAM-1 blocking
antibody abolishes the KCa3.1-dependent increase in adhesion. Senicapoc inhibits
transendothelial migration of A549 cells by 50%. Selectively silencing KCa3.1
channels in either NSCLC or endothelial cells reveals that transendothelial
migration depends predominantly on endothelial KCa3.1 channels. In conclusion,
our findings disclose a novel function of KCa3.1 channels in cancer. KCa3.1
channels regulate ICAM-1 dependent cell-cell adhesion between endothelial and
cancer cells that affects the transmigration step of the metastatic cascade.
PMID- 29348825
TI - A novel anti-CD146 antibody specifically targets cancer cells by internalizing
the molecule.
AB - CD146 is an adhesion molecule present on many tumors (melanoma, kidney, pancreas,
breast, ...). In addition, it has been shown to be expressed on vascular
endothelial and smooth muscle cells. Generating an antibody able to specifically
recognize CD146 in cancer cells (designated as tumor CD146), but not in normal
cells, would thus be of major interest for targeting tumor CD146 without
affecting the vascular system. We thus generated antibodies against the
extracellular domain of the molecule produced in cancer cells and selected an
antibody that specifically recognizes tumor CD146. This antibody (TsCD146 mAb)
was able to detect CD146-positive tumors in human biopsies and in vivo, by PET
imaging, in a murine xenograft model. In addition, TsCD146 mAb antibody was able
to specifically detect CD146-positive cancer microparticles in the plasma of
patients. TsCD146 mAb displayed also therapeutic effects since it was able to
reduce the growth of human CD146-positive cancer cells xenografted in nude mice.
This effect was due to a decrease in the proliferation and an increase in the
apoptosis of CD146-positive cancer cells after TsCD146-mediated internalization
of the cell surface CD146. Thus, TsCD146 mAb could be of major interest for
diagnostic and therapeutic strategies against CD146-positive tumors in a context
of personalized medicine.
PMID- 29348826
TI - Interaction of macrophages with apoptotic cells inhibits transdifferentiation and
invasion of lung fibroblasts.
AB - The invasion of activated fibroblasts is a key mechanism of tissue fibrosis
pathology. The recognition and uptake of apoptotic cells can induce the anti
fibrogenic programming of macrophages. We demonstrate that after interacting with
apoptotic cells, macrophages secrete bioactive molecules that antagonize TGF
beta1-induced increases in myofibroblast (fibroproliferative) phenotypic markers
and reduce the enhanced invasive capacity of TGF-beta1- or EGF-treated mouse lung
fibroblasts (MLg). Furthermore, numerous treatment strategies prevented the anti
fibrotic effects of conditioned media, including transfection of macrophages with
COX-2 or RhoA siRNAs or treatment of MLg cells with receptor antagonists for
prostaglandin E2 (PGE2), PGD2, or hepatocyte growth factor (HGF). Additionally,
administration of apoptotic cells in vivo inhibited the bleomycin-mediated
invasive capacity of primary fibroblasts, as well as adhesion and extracellular
matrix protein mRNA expression. These data suggest that the anti-fibrogenic
programming of macrophages by apoptotic cells can be used as a novel tool to
control the progressive fibrotic reaction.
PMID- 29348827
TI - Molecular-genetic profiling and high-throughput in vitro drug screening in NUT
midline carcinoma-an aggressive and fatal disease.
AB - NUT midline carcinoma (NMC) is a rare and aggressive cancer, with survival
typically less than seven months, that can arise in people of any age.
Genetically, NMC is defined by the chromosomal fusion of NUTM1 with a chromatin
binding partner, typically the bromodomain-containing protein BRD4. However,
little is known about other genetic aberrations in this disease. In this study,
we used a unique panel of cell lines to describe the molecular-genetic features
of NMC. Next-generation sequencing identified a recurring high-impact mutation in
the DNA-helicase gene RECQL5 in 75% of lines studied, and biological signals from
mutation-signature and network analyses consistent with a general failure in DNA
repair. A high-throughput drug screen confirmed that microtubule inhibitors,
topoisomerase inhibitors and anthracyclines are highly cytotoxic in the majority
of NMC lines, and that cell lines expressing the BRD4-NUTM1 (exon11:exon2)
variant are an order of magnitude more responsive to bromodomain inhibitors
(iBETs) on average than those with other BRD4-NUTM1 translocation variants. We
also identified a highly significant correlation between iBET and aurora kinase
inhibitor efficacy in this study. Integration of exome sequencing, transcriptome,
and drug sensitivity profiles suggested that aberrant activity of the nuclear
receptor co-activator NCOA3 may correlate with poor response to iBETs. In
conclusion, our data emphasize the heterogeneity of NMC and highlights genetic
aberrations that could be explored to improve therapeutic strategies. The novel
finding of a recurring RECQL5 mutation, together with recent reports of
chromoplexy in this disease, suggests that DNA-repair pathways are likely to play
a central role in NMC tumorigenesis.
PMID- 29348828
TI - Dose escalation by image-guided intensity-modulated radiotherapy leads to an
increase in pain relief for spinal metastases: a comparison study with a regimen
of 30 Gy in 10 fractions.
AB - Purpose: Under the existing condition that the optimum radiotherapy regimen for
spinal metastases is controversial, this study investigates the benefits of dose
escalation by image-guided intensity-modulated radiotherapy (IG-IMRT) with 60-66
Gy in 20-30 fractions for spinal metastases. Results: In the dose-escalation
group, each D50 of planning gross tumor volume (PGTV) was above 60 Gy and each
Dmax of spinal cord planning organ at risk volume (PRV) was below 48 Gy. The
median biological effective dose (BED) of Dmax of spinal cord was lower in the
dose-escalation group compared with that in the 30-Gy group (69.70 Gy vs. 83.16
Gy, p < 0.001). After one month and three months of the radiotherapy, pain
responses were better in the dose-escalation group than those in the 30-Gy group
(p = 0.005 and p = 0.024), and the complete pain relief rates were respectively
73.69% and 34.29% (p = 0.006), 73.69% and 41.38% (p = 0.028) in two compared
groups. In the dose-escalation group, there is a trend of a longer duration of
pain relief, a longer overall survival and a lower incidence of acute radiation
toxicities. No late radiation toxicities were observed in both groups. Materials
and Methods: Dosimetric parameters and clinical outcomes, including pain
response, duration of pain relief, radiation toxicities and overall survival,
were compared among twenty-five metastatic spinal lesions irradiated with the
dose-escalation regimen and among forty-four lesions treated with the 30-Gy
regimen. Conclusions: Conventionally-fractionated IG-IMRT for spinal metastases
could escalate dose to the vertebral lesions while sparing the spinal cord,
achieving a better pain relief without increasing radiation complications.
PMID- 29348829
TI - Roflumilast restores cAMP/PKA/CREB signaling axis for FtMt-mediated tumor
inhibition of ovarian cancer.
AB - The abrogation of cAMP generation by overexpression of PDE isoforms promotes the
inflammatory pathology, and the PDE inhibitors have showed the potential anti
inflammation effects in clinical. However, the function of PDE inhibitors in
cancer treatment remains unclear. We here investigated the role of PDE4 inhibitor
Roflumilast in the treatment of ovarian cancer. We found that Roflumilast could
effectively inhibit the proliferation, and induce apoptosis and cell cycle arrest
in two ovarian cancer cell lines OVCAR3 and SKOV3. Meanwhile, the cAMP/PKA/CREB
signals was activated by Roflumilast, which was accompanied by the up-regulation
of mitochondrial ferritin (FtMt) level. Interestingly, forced expression of FtMt
in ovarian cancer enhanced the apoptosis and inhibited tumor growth and the PKA
inhibitor H89 and knockdown of CREB significantly repressed the expression of
FtMt to restore the tumor proliferation and inhibit apoptosis. In addition, we
found that Roflumilast-induced phosphorylated CREB directly promoted
transcription of FtMt, indicating that Roflumilast up-regulated the expression of
FtMt in ovarian cancer via cAMP/PKA/CREB signals. The anti-tumor role of
Roflumilast in vivo was also demonstrated, the treatment of roflumilast
effectively inhibited tumor proliferation and elevated the FtMt expression to
restrict the tumor growth via the activation of cAMP/PKA/CREB signals in ovarian
cancer.
PMID- 29348830
TI - Inactivation/deficiency of DHODH induces cell cycle arrest and programed cell
death in melanoma.
AB - Malignant melanoma (MM) is one of the most malignant tumors and has a very poor
prognosis. However, there are no effective drugs to treat this disease. As a kind
of iron flavin dependent enzyme, dihydroorotate dehydrogenase (DHODH, EC 1.3.3.1)
is the fourth and a key enzyme in the de novo biosynthesis of pyrimidines.
Herein, we found that DHODH inactivation/deficiency inhibited melanoma cell
proliferation, induced cell cycle arrest at S phase and lead to autophagy in
human melanoma cells. Meanwhile, leflunomide treatment induced cell apoptosis and
deficiency of DHODH sensitized cells to drug-induced apoptosis in BCL-2 deficient
melanoma cells, while not in BCL-2 abundant melanoma cells. Then we found that
BCL-2 could rescue apoptosis induced by DHODH inactivation/deficiency. Moreover,
BCL-2 also showed to promote cell cycle arrest and to inhibit autophagy induced
by leflunomide. To explore the mechanisms underlying autophagy induced by DHODH
inhibition, we found that AMPK-Ulk1 axis was activated in this process. Besides,
JNK was phosphorylated and activated to phosphorylate BCL-2, which abrogated the
interaction between BCL-2 and Beclin1 and then abolished autophagy. Our findings
provided evidences for the potential of DHODH used as a drug target for melanoma
treatment.
PMID- 29348831
TI - Aberrant expression of miR-21, miR-376c and miR-145 and their target host genes
in Merkel cell polyomavirus-positive non-small cell lung cancer.
AB - Merkel Cell Polyoma Virus (MCPyV) infection has been associated with non-small
cell lung cancer (NSCLC). Viruses can manipulate cellular miRNAs or have a
profound impact on cellular miRNA expression to control host regulatory pathways.
In this study, we evaluated the expression profiles of cancer-associated and
virally affected host microRNAs miR-21, miR-145, miR-146a, miR-155, miR-302c, miR
367 and miR-376c in a series of NSCLC tissue samples as well as in samples from
"healthy" sites, distant from the tumour region that were either positive or
negative for MCPyV DNA. miR-21 and miR-376c were significantly upregulated
whereas miR-145 was significantly downregulated in the MCPyV+ve samples compared
to the MCPyV-ve tumour samples. Overall, miR-21 and miR-376c expression was
higher in tumour compared to healthy tissue samples. No association was observed
between the miR-155, miR-146a, miR-302c and miR-367 levels and the presence of
MCPyV. The expression of miR-21 target genes (Pten, Bcl-2, Daxx, Pkr, Timp3), miR
376c (Grb2, Alk7, Mmp9) and miR-145 (Oct-4, Sox2, Fascin1) and their associated
pathways (Braf, Akt-1, Akt-2, Bax, Hif1a, p53) was altered between MCPyV+ve tumor
samples and their corresponding controls. These results show a novel association
between miR-21, miR-376c and miR-145 and their host target genes with the
presence of MCPyV, suggesting a mechanism of virus-specific microRNA signature in
NSCLC.
PMID- 29348832
TI - Clinical and histological features of primary testicular diffuse large B-cell
lymphoma: a single center experience in China.
AB - Primary testicular lymphoma (PTL) is a rare and aggressive form of extranodal
lymphoma. Approximately 80-98% of PTLs are diffuse large B-cell lymphoma (PT
DLBCL). The prognosis of DLBCL patients has improved with the addition of
rituximab to systemic chemotherapy, but outcomes of PT-DLBCL remain poor. This
may be explained by the high rate of relapse in the central nervous system (CNS)
and contralateral testis. We analyzed 1,132 newly diagnosed DLBCL patients (37
with PT-DLBCL) who were treated at our hospital between January 2009 and December
2014. Twenty-five patients finished follow-up. We analyzed clinical
characteristics, response to chemotherapy, overall survival, and relapse in the
CNS and contralateral testis. All patients underwent orchiectomy. The median age
was 60 (range: 43-82) years. Eleven patients had stage III/IV disease. Five
patients experienced CNS relapse, and three experienced relapse in the
contralateral testis. Median overall survival (OS) was not reached at the time of
reporting. The 3-year OS rate was 57%. None of the nine patients who received
radiotherapy to the contralateral testis experienced relapse in that location.
Intrathecal prophylaxis did not reduce the risk of CNS relapse. All five patients
who experienced CNS relapse had the germinal center B-cell-like subtype of DLBCL.
PMID- 29348833
TI - Gold nanoparticles as a potent radiosensitizer in neutron therapy.
AB - The purpose of this study was to investigate the potential of gold nanoparticles
as radiosensitizer for use in neutron therapy against hepatocellular carcinoma.
The hepatocellular carcinoma cells lines Huh7 and HepG2 were irradiated with
gamma and neutron radiation in the presence or absence of gold nanoparticles.
Effects were evaluated by transmission electron microscopy, cell survival, cell
cycle, DNA damage, migration, and invasiveness. Gold nanoparticles significantly
enhanced the radiosensitivity of Huh7 and HepG2 cells to gamma-rays by 1.41- and
1.16-fold, respectively, and by 1.80- and 1.35-fold to neutron radiation, which
has high linear energy transfer. Accordingly, exposure to neutron radiation in
the presence of gold nanoparticles induced cell cycle arrest, DNA damage, and
cell death to a significantly higher extent, and suppressed cell migration and
invasiveness more robustly. These effects are presumably due to the ability of
gold nanoparticles to amplify the effective dose from neutron radiation more
efficiently. The data suggest that gold nanoparticles may be clinically useful in
combination therapy against hepatocellular carcinoma by enhancing the toxicity of
radiation with high linear energy transfer.
PMID- 29348835
TI - Simultaneous quantification of DNA damage and mitochondrial copy number by long
run DNA-damage quantification (LORD-Q).
AB - DNA damage and changes in the mitochondrial DNA content have been implicated in
ageing and cancer development. To prevent genomic instability and tumorigenesis,
cells must maintain the integrity of their nuclear and mitochondrial DNA.
Advances in the research of DNA damage protection and genomic stability, however,
also depend on the availability of techniques that can reliably quantify
alterations of mitochondrial DNA copy numbers and DNA lesions in an accurate high
throughput manner. Unfortunately, no such method has been established yet. Here,
we describe the high-sensitivity long-run real-time PCR technique for DNA-damage
quantification (LORD-Q) and its suitability to simultaneously measure DNA damage
rates and mitochondrial DNA copy numbers in cultured cells and tissue samples.
Using the LORD-Q multiplex assay, we exemplarily show that the mitochondrial DNA
content does not directly affect DNA damage susceptibility, but influences the
efficacy of certain anticancer drugs. Hence, LORD-Q provides a fast and precise
method to assess DNA lesions, DNA repair and mtDNA replication as well as their
role in a variety of pathological settings.
PMID- 29348834
TI - Activity strengths of cortical glutamatergic and GABAergic neurons are correlated
with transgenerational inheritance of learning ability.
AB - The capabilities of learning and memory in parents are presumably transmitted to
their offsprings, in which genetic codes and epigenetic regulations are thought
as molecular bases. As neural plasticity occurs during memory formation as
cellular mechanism, we aim to examine the correlation of activity strengths at
cortical glutamatergic and GABAergic neurons to the transgenerational inheritance
of learning ability. In a mouse model of associative learning, paired whisker and
odor stimulations led to odorant-induced whisker motion, whose onset appeared
fast (high learning efficiency, HLE) or slow (low learning efficiency, LLE). HLE
male and female mice, HLE female and LLE male mice as well as HLE male and LLE
female mice were cross-mated to have their first generation of offsprings,
filials (F1). The onset of odorant-induced whisker motion appeared a sequence of
high-to-low efficiency in three groups of F1 mice that were from HLE male and
female mice, HLE female and LLE male mice as well as HLE male and LLE female
mice. Activities related to glutamatergic neurons in barrel cortices appeared a
sequence of high-to-low strength in these F1 mice from HLE male and female mice,
HLE female and LLE male mice as well as HLE male and LLE female mice. Activities
related to GABAergic neurons in barrel cortices appeared a sequence of low-to
high strength in these F1 mice from HLE male and female mice, HLE female and LLE
male mice as well as HLE male and LLE female mice. Neuronal activity strength was
linearly correlated to learning efficiency among three groups. Thus, the
coordinated activities at glutamatergic and GABAergic neurons may constitute the
cellular basis for the transgenerational inheritance of learning ability.
PMID- 29348836
TI - Vitexin confers HSF-1 mediated autophagic cell death by activating JNK and ApoL1
in colorectal carcinoma cells.
AB - Heat shock transcription factor-1 (HSF-1) guards the cancerous cells proteome
against the alterations in protein homeostasis generated by their hostile tumor
microenvironment. Contrasting with the classical induction of heat shock
proteins, the pro-oncogenic activities of HSF-1 remains to be explored.
Therefore, cancer's fragile proteostatic pathway governed by HSF-1 could be a
potential therapeutic target and novel biomarker by natural compounds. Vitexin, a
natural flavonoid has been documented as a potent anti-tumor agent on various
cell lines. However, in the present study, when human colorectal carcinoma HCT
116 cells were exposed to vitexin, the induction of HSF-1 downstream target
proteins, such as heat shock proteins were suppressed. We identified HSF-1 as a
potential molecular target of vitexin that interact with DNA-binding domain of
HSF-1, which inhibited HSF-1 oligomerization and activation (in silico).
Consequently, HSF-1 hyperphosphorylation mediated by JNK operation causes
transcriptional inactivation of HSF-1, and supported ROS-mediated autophagy
induction. Interestingly, in HSF-1 immunoprecipitated and silenced HCT-116 cells,
co-expression of apolipoprotein 1 (ApoL1) and JNK was observed which promoted the
caspase independent autophagic cell death accompanied by p62 downregulation and
increased LC3-I to LC3-II conversion. Finally, in vivo findings confirmed that
vitexin suppressed tumor growth through activation of autophagic cascade in HCT
116 xenograft model. Taken together, our study insights a probable novel
association between HSF-1 and ApoL-1 was established in this study, which
supports HSF-1 as a potential target of vitexin to improve treatment outcome in
colorectal cancer.
PMID- 29348837
TI - Combined surgery and radiation improves survival of tonsil squamous cell cancers.
AB - Objective: The study evaluated the addition of surgery (S) to radiation (RT) on
survival of squamous cell carcinomas (SCC) of tonsillar-fossa (TF) in a modern
cohort with similar epidemiology and treatment as current patients. Study Design:
Retrospective analysis utilizing Surveillance, Epidemiology, and End Results
(SEER) Program data. Results: For all stages combined TF patients who received
S+RT had superior OS (p < 0.01) and DSS (p < 0.01). For each stage OS and DSS was
superior for S+RT (p < 0.05). In multivariate analysis, HRs for OS were
statistically significantly higher for TF patients (stage 2, 3, and 4) receiving
RT alone (p < 0.001). Materials and Methods: TF SCC patients treated with either
S+RT or RT alone between 2004 and 2011 were examined (n = 6,476). Primary outcome
measures included overall survival (OS) and disease specific survival (DSS). Cox
proportional hazard ratios (HR) were estimated for patients treated with S+RT
compared to RT alone. Conclusions: OS and DSS were superior for all stages
combined and for stages 2, 3, and 4 in TF patients who received S+RT compared to
RT alone.
PMID- 29348838
TI - Single nucleotide polymorphisms in ZNF208 are associated with increased risk for
HBV in Chinese people.
AB - Single nucleotide polymorphisms (SNPs) in ZNF208 may be associated with
susceptibility to Hepatitis B virus (HBV). In the current study, we analyzed the
association between ZNF208 SNPs and risk of HBV in 242 HBV patients and 300
healthy subjects from the Xi'an area of Chinese Han Population. Of the five SNPs
examined, rs2188971 (OR: 1.36, 95% CI: 1.04-1.76, P = 0.022), rs8103163 (OR:
1.40, 95% CI: 1.08-1.82, P = 0.010) and rs7248488 (OR: 1.38, 95% CI: 1.07-1.79, P
= 0.014) were correlated with HBV susceptibility based on Chi-square tests. After
the P-values were adjusted by Bonferroni correction, there only rs8103163 (P =
0.050) was slightly with increased HBV risk. Additionally, haplotype
Ars2188972Trs2188971Ars8103163Ars7248488 (OR = 1.42; 95% C I, 1.10-1.85; P =
0.008) was found to increase susceptibility of suffering from HBV. These findings
suggest that ZNF208 polymorphisms may contribute to the development of HBV.
PMID- 29348839
TI - Differences in the expression of long noncoding RNAs at different time points in
the PTSD-like syndrome rat hippocampus.
AB - The aim of this study was to characterize the expression profiles at different
time points in the PTSD-like syndrome rat hippocampus and perform analyses. PTSD
rat models were made as reported by Rau, and we collected the hippocampus at
different time points. The lncRNAs at different time points were compared by
microarray and listed. We used quantitative real-time PCR to confirm the lncRNA
profiling expression data. Bioinformatics analysis was performed on EU056364_P1.
Compare with control, a total of 948 lncRNAs and 2514 mRNAs were found (fold
change > 2.0) among the four time points. Additionally, bioinformatics analysis
of EU056364_P1 suggested it might be involved in memory development through the
target gene Camk2a.This study revealed different lncRNAs expressed at different
time points in PTSD and explored the targets of PTSD.
PMID- 29348840
TI - The prevalence of and risk factors for diabetes mellitus and impaired glucose
tolerance among Tibetans in China: a cross-sectional study.
AB - The prevalence of diabetes mellitus (DM) and impaired glucose tolerance (IGT) has
increased worldwide, although their prevalence and determinants among Tibetans
are currently unknown. We thus aimed to explore the prevalence of and risk
factors for DM and IGT among Tibetans in China. In 2011, 1659 Tibetan adults
(aged >= 18 years) from Changdu, China, were recruited to this cross-sectional
study. They completed a questionnaire and underwent physical examinations and
laboratory testing to assess risk factors for DM and IGT. The age-standardized
prevalence of DM and IGT among Tibetans was 6.2% and 19.7%, respectively. A
higher annual family income, alcohol consumption, and higher fasting plasma
glucose (FPG) level were risk factors for DM, with odds ratio (ORs) and 95%
confidence intervals (CIs) of 3.48 (1.43-8.48; P = 0.006) for those with family
incomes of > 1600 USD/year, 3.06 (1.31-7.17; P = 0.010) for alcohol consumption,
and 13.99 (7.76-25.22; P < 0.001) for FPG level. However, altitude was found to
be negatively associated with the risk of DM; compared to individuals living at <
3500 meters, the risk of DM decreased by 65% for those living at 3500-3999 meters
(P = 0.034) and by 89% for those living at >= 4000 meters (P = 0.015). Age, FPG
levels, and low-density lipoprotein cholesterol levels were significantly
associated with IGT among Tibetans aged >= 18 years. These findings suggest that
the prevalence of DM in Tibetans may continue to increase in future decades
following rapid economic development, and it is crucial to address the management
of conventional risk factors for reducing the disease burden of DM among
Tibetans.
PMID- 29348841
TI - Activation of AMPK by OSU53 protects spinal cord neurons from oxidative stress.
AB - The present study tested the potential effect of OSU53, a novel AMPK activator,
against hydrogen peroxide (H2O2)-induced spinal cord neuron damages. Treatment
with OSU53 attenuated H2O2-induced death and apoptosis of primary murine spinal
cord neurons. OSU53 activated AMPK signaling, which is required for its actions
in spinal cord neurons. The AMPK inhibitor Compound C or AMPKalpha1 siRNA almost
abolished OSU53-mediated neuroprotection against H2O2. On the other hand,
sustained-activation of AMPK by introducing the constitutive-active AMPKalpha1
mimicked OSU53's actions, and protected spinal cord neurons from oxidative
stress. OSU53 significantly attenuated H2O2-induced reactive oxygen species
production, lipid peroxidation and DNA damages in spinal cord neurons.
Additionally, OSU53 increased NADPH content and heme oxygenase-1 mRNA expression
in H2O2-treated spinal cord neurons. Together, we indicate that targeted
activation of AMPK by OSU53 protects spinal cord neurons from oxidative stress.
PMID- 29348842
TI - DDEFL1 correlated with Rho GTPases activity in breast cancer.
AB - DDEFL1 is related to maintaining a limiting amount of ARF6 in GTP-loaded form by
accelerating its GTP hydrolysis activity, which has been implicated in
hepatocellular cancer pathogenesis and lung cancer development. We investigated
DDEFL1 expression in breast cancer and paired normal breast tissues by
immunohistochemistry and found that DDEFL1 expression was significantly
associated with tumor size, lymph node metastasis, high content of elastosis and
TNM stage but not with menopausal status or age. We detected the mRNA and protein
expression of DDEFL1 in breast cancer cell lines by Western blotting and
quantitative real-time PCR (qRT-PCR). DDEFL1 was obvious in MDA-MB-435s and MDA
MB-231 but very weak in ZR-75-1. Further experiments were conducted to evaluate
the effect of DDEFL1 small interfering RNA (siRNA) transfection on the biological
behavior of MDA-MB-231. After transfection, the effects of DDEFL1 inhibition on
expression of mRNA and protein were also analyzed by Western blotting and qRT
PCR. Increased apoptosis and invasive ability, decreased cellular proliferation
was found in MDA-MB-231 with successful DDEFL1 siRNA transient transfection (p <
0.05). Western blotting and qRT-PCR results showed that the DDEFL1 inhibition up
regulated Caspase-3, Apaf-1, cytochrome c, and Bax expression and down-regulated
Bcl-2 expression. The DDEFL1 inhibition also down-regulated the mRNA and protein
expression of Rho, CDC42 and Rac1. Our study provided a functional linkage
through DDEFL1 with breast cancer biological behaviours by Rho GTPases. Possible
implication of our main finding for the DDEFL1 role in breast cancer and the
downstream signaling pathways for the treatment of breast cancer.
PMID- 29348843
TI - Actein induces autophagy and apoptosis in human bladder cancer by potentiating
ROS/JNK and inhibiting AKT pathways.
AB - Human bladder cancer is a common genitourinary malignant cancer worldwide.
However, new therapeutic strategies are required to overcome its stagnated
survival rate. Triterpene glycoside Actein (ACT), extracted from the herb black
cohosh, suppresses the growth of human breast cancer cells. Our study attempted
to explore the role of ACT in human bladder cancer cell growth and to reveal the
underlying molecular mechanisms. We found that ACT significantly impeded the
bladder cancer cell proliferation via induction of G2/M cycle arrest.
Additionally, ACT administration triggered autophagy and apoptosis in bladder
cancer cells, proved by the autophagosome formation, LC3B-II accumulation,
improved cleavage of Caspases/poly (ADP-ribose) polymerase (PARP). Furthermore,
reduction of reactive oxygen species (ROS) and p-c-Jun N-terminal kinase (JNK)
could markedly reverse ACT-induced autophagy and apoptosis. In contrast, AKT and
mammalian target of rapamycin (mTOR) were greatly de-phosphorylated by ACT, while
suppressing AKT and mTOR activity could enhance the effects of ACT on apoptosis
and autophagy induction. In vivo, ACT reduced the tumor growth with little
toxicity. Taken together, our findings indicated that ACT suppressed cell
proliferation, induced autophagy and apoptosis through promoting ROS/JNK
activation, and blunting AKT pathway in human bladder cancer, which indicated
that ACT might be an effective candidate against human bladder cancer in future.
PMID- 29348844
TI - Trends and variations in mantle cell lymphoma incidence from 1995 to 2013: A
comparative study between Texas and National SEER areas.
AB - Background: Few studies have assessed mantle cell lymphoma (MCL) incidence trends
in the U.S. National Cancer Institute's Surveillance, Epidemiology and End
Results (SEER) areas. Previous studies were 5 to 9 years old and MCL incidence in
Texas remains unknown. This study updated the temporal trends and variations of
MCL incidence in the SEER areas and compared them with counterpart data in Texas.
Results: From 1995 to 2013, there were 2, 435 and 5, 193 newly diagnosed MCL
patients in Texas and SEER areas. Age-adjusted MCL incidence was 0.91 per 100,000
persons per year in Texas and 1.01 in SEER areas. MCL incidence increased
steadily with an annual percent change (APC) of 2.56% in SEER areas and an APC of
2.16% in Texas. In SEER areas, APCs for MCL incidence were significantly
different from zero in patients with advanced stage tumor (3.33%), male (2.71%),
elderly patients >= 80 years old (4.21%) and non-Hispanic white patients (2.83%)
(all P < 0.05). Similar patterns were found in Texas for both incidence rates and
APCs. Materials and methods: We identified all adult patients with newly
diagnosed MCL in Texas Cancer Registry and SEER databases from 1995 to 2013. Age
adjusted incidence rates were calculated and negative binomial regression model
was used to assess the factors associated with MCL incidence. Conclusions: MCL
incidence rates increased over time in both Texas and SEER areas, with increases
being greater in male, non-Hispanic white, and elderly patient >=70 years with
advanced stage tumors. Texas has similar MCL incidence trends and disparities as
the national SEER areas.
PMID- 29348845
TI - Decreased expression of the long non-coding RNA SLC7A11-AS1 predicts poor
prognosis and promotes tumor growth in gastric cancer.
AB - Many lncRNA and mRNA sense-antisense transcripts have been systematically
identified in malignant cells. However, the molecular mechanisms of most lncRNA
mRNA pairs in gastric cancer remain largely unknown. We found the gastric cancer
associated lncRNA SLC7A11-AS1 and coding transcript mRNA SLC7A11 in human gastric
cancer specimens by microarray. SLC7A11-AS1, antisense to SLC7A11, is
significantly down-regulated in gastric cancer and could promote tumor growth in
vitro and in vivo. The effects of SLC7A11-AS1 depend on the regulation of SLC7A11
via the ASK1-p38MAPK/JNK signaling pathway. These findings suggest that decreased
expression of SLC7A11-AS1 contributes to the progression of gastric cancer and
may be a novel diagnostic biomarker and effective therapeutic target in gastric
cancer patients.
PMID- 29348846
TI - ST6GALNAC1 plays important roles in enhancing cancer stem phenotypes of
colorectal cancer via the Akt pathway.
AB - Colorectal cancer (CRC) is a mortal disease due to treatment resistance,
recurrence and distant metastasis. Emerging evidence has revealed that a small
sub-population of cancer cells termed cancer stem cells (CSCs)/ cancer-initiating
cells (CICs) is endowed with high levels of tumor-initiating ability, self
renewal ability and differentiation ability and is responsible for treatment
resistance, recurrence and distant metastasis. Eradication of CSCs/CICs is
essential to improve current treatments. However, the molecular mechanisms by
which CSCs/CICs are maintained are still elusive. In this study, we aimed to
determine the molecular mechanisms by which colorectal (CR)-CSCs/CICs in are
maintained human primary CRC cells. CR-CSCs/CICs were isolated by sphere-culture
and the ALDEFLUOR assay, and transcriptome analysis revealed that the gene ST6 N
Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) was expressed at
high levels in CR-CSCs/CICs. Overexpression of ST6GALNAC1 enhanced the expression
of sialyl-Tn (STn) antigen, which is carried by the CSC marker CD44, and
increased the sphere-forming ability and resistance to a chemotherapeutic
reagent. The opposite phenomena were observed by gene knockdown using siRNA.
Furthermore, the Akt pathway was activated in ST6GANAC1-overexpressed cells, and
activation of the pathway was cancelled by gene knockdown of galectin-3. The
results indicate that ST6GALNAC1 has a role in the maintenance of CR-CSCs/CICs by
activating the Akt pathway in cooperation with galectin-3 and that ST6GalNAC1 (or
STn antigen) might be a reasonable molecule for CSC/CIC-targeting therapy.
PMID- 29348847
TI - Distinct roles of TRAF6 and TAK1 in the regulation of adipocyte survival,
thermogenesis program, and high-fat diet-induced obesity.
AB - Chronic low-grade inflammation, adipocyte hypertrophy, and glucose intolerance
are common features of obesity and a risk factor for cancer. Tumor necrosis
factor (TNF) receptor-associated factor 6 (TRAF6) is an adaptor protein that also
possesses a non-conventional E3 ubiquitin ligase activity. In response to
receptor-mediated events, TRAF6 activates transforming growth factor-activated
kinase 1 (TAK1), which leads to activation of the MAPK and nuclear factor-kappa B
(NF-kappaB) signaling pathways. However, the roles of TRAF6 and TAK1 in the
regulation of adipocyte function remain less understood. Here, we demonstrate
that adipocyte-specific deletion of TAK1, but not TRAF6, in mice reduces the
survival of adipocytes and abundance of white adipose tissue (WAT). Adipocyte
specific ablation of TAK1, but not TRAF6, increases the expression for markers of
beige/brown fat in WAT. Deletion of TAK1 in WAT increases phosphorylation of
AMPK, abundance of PGC-1alpha, non-canonical NF-kappaB signaling, markers of M2
macrophages, and diminishes phosphorylation of JNK and canonical NF-kappaB
signaling. Levels of TRAF6 and enzymatic activity of TAK1 are increased in WAT of
mice fed with high-fat diet (HFD). Our results demonstrate that ablation of TAK1
drastically reduces HFD-induced obesity and improves energy expenditure and
glucose metabolism. In contrast, adipocyte-specific ablation of TRAF6 has a
minimal effect on HFD-induced obesity. Collectively, our results suggest that
even though TRAF6 is an upstream activator of TAK1 in many signaling cascades,
inactivation of TAK1, but not TRAF6, regulates adipocyte survival, energy
expenditure, and HFD-induced obesity in mice.
PMID- 29348848
TI - PD-L1 expression in tumor tissue and peripheral blood of patients with oral
squamous cell carcinoma.
AB - Background: Immune checkpoints like programmed cell death-1 (PD-1) and its ligand
PD-L1 are involved in immune escape mechanisms of solid tumors including oral
squamous cell carcinoma (OSCC). Inhibitors of the pathway are successfully used
for treating especially advanced disease. However, the physiological relevance of
PD-1/PD-L1-signaling in OSCC is insufficiently understood. The aim of the study
was to analyze if PD-L1 expression in tumor tissue and peripheral blood samples
of OSCC patients is associated with histomorphological tumor parameters and if PD
L1 expression in patients is different from controls. Results: OSCC tumor
specimens showed a significantly higher PD-L1 expression than oral mucosa
controls (p < 0.001; upregulation more than 3-fold). Cross-tabulation revealed an
association of increased expression of PD-L1 mRNA in tissue specimens with
malignancy (p < 0.001).OSCC cases with higher tumor grade and cases with lymph
node metastases (N+) were significantly (p < 0.05) associated with increased PD
L1 expression in peripheral blood. Cross-tabulation revealed an significant
association with lymph node metastases (N+) (p <= 0.002). Materials and Methods:
PD-L1 mRNA expression was analyzed in tumor specimens and corresponding samples
of healthy oral mucosa and peripheral blood of 45 OSCC patients and 36 healthy
control persons using RT-qPCR analysis. A Mann-Whitney U-test, a cut-off point
analysis and a Chi-square test were carried out. Conclusions: PD-L1 expression in
OSCC could contribute to the immunosuppressive local tumor microenvironment.
Increased malignant behavior (higher tumor grade, positive nodal status) might be
associated with PD-L1 mediated systemic immune tolerance. Thus, PD-L1 expression
in peripheral blood might be an indicator of the existence of metastatic disease
(N+) in OSCC.
PMID- 29348849
TI - Reduced levels of N'-methyl-2-pyridone-5-carboxamide and lysophosphatidylcholine
16:0 in the serum of patients with intrahepatic cholangiocarcinoma, and the
correlation with recurrence-free survival.
AB - We searched for metabolic biomarkers that may predict the prognosis of patients
with intrahepatic cholangiocarcinoma (IHCC). To this end, a total of 237 serum
samples were obtained from IHCC patients (n = 87) and healthy controls (n = 150),
and serum metabolites were analyzed by liquid chromatography-tandem mass
spectrometry (LC-MS/MS). Two stratified algorithms were used to select the
metabolites, the levels of which predicted the prognosis of IHCC patients. We
performed MS/MS and multiple-reaction-monitoring MS analyses to identify and
quantify the selected metabolites. Continuous biomarker levels were dichotomized
based on cutoffs that maximized between-group differences in recurrence-free
survival (RFS) in terms of the log-rank test statistic. These RFS differences
were analyzed using the log-rank test, and survival curves were drawn with the
aid of the Kaplan-Meier method. Six metabolites (l-glutamine,
lysophosphatidylcholine [LPC] 16:0, LPC 18:0, N'-methyl-2-pyridone-5-carboxamide
[2PY], fibrinopeptide A [FPA] and uric acid) were identified as candidate
metabolic biomarkers for predicting the prognosis of IHCC patients. Of these
metabolites, levels of l-glutamine, uric acid, LPC 16:0, and LPC 18:0 were
significantly lower in the serum from IHCC patients, whereas levels of 2PY and
FPA were significantly higher (p < 0.01). 2PY and LPC 16:0 showed significantly
better RFS at low level than high level (2PY, median RFS: 15.16 months vs. 5.90
months, p = 0.037; LPC 16:0, median RFS: 15.62 months vs. 9.83 months, p =
0.035). The findings of this study suggest that 2PY and LPC 16:0 identified by
metabolome-based approaches may be useful biomarkers for IHCC patients.
PMID- 29348850
TI - Novel indazole-based small compounds enhance TRAIL-induced apoptosis by
inhibiting the MKK7-TIPRL interaction in hepatocellular carcinoma.
AB - Hepatocellular carcinoma (HCC) is one of the most malignant tumors. Although
various treatments, such as surgery and chemotherapy, have been developed, a
novel alternative therapeutic approach for HCC therapy is urgently needed. Tumor
necrosis factor-related apoptosis inducing ligand (TRAIL) is a promising anti
cancer agent, but many cancer cells are resistant to TRAIL-induced apoptosis. To
help overcome TRAIL resistance in HCC cancer cells, we have identified novel
chemical compounds that act as TRAIL sensitizers. We first identified the hit
compound, TRT-0002, from a chemical library of 6,000 compounds using a previously
developed high-throughput enzyme-linked immunosorbent assay (ELISA) screening
system, which was based on the interaction of mitogen-activated protein kinase
kinase 7 (MKK7) and TOR signaling pathway regulator-like (TIPRL) proteins and a
cell viability assay. To increase the efficacy of this TRAIL sensitizer, we
synthesized 280 analogs of TRT-0002 and finally identified two lead compounds
(TRT-0029 and TRT-0173). Co-treating cultured Huh7 cells with either TRT-0029 or
TRT-0173 and TRAIL resulted in TRAIL-induced apoptosis due to the inhibition of
the MKK7-TIPRL interaction and subsequent phosphorylation of MKK7 and c-Jun N
terminal kinase (JNK). In vivo, injection of these compounds and TRAIL into HCC
xenograft tumors resulted in tumor regression. Taken together, our results
suggest that the identified lead compounds serve as TRAIL sensitizers and
represent a novel strategy to overcome TRAIL resistance in HCC.
PMID- 29348851
TI - Comprehensive analysis of mRNA-lncRNA co-expression profile revealing crucial
role of imprinted gene cluster DLK1-MEG3 in chordoma.
AB - Chordoma is a rare bone tumor with high recurrence rate, but the mechanism of its
development is unclear. Long non-coding RNAs(lncRNAs) are recently revealed to be
regulators in a variety of biological processed by targeting on mRNA
transcription. Their expression profile and function in chordoma have not been
investigated yet. In this study, we firstly performed the comprehensive analysis
of the lncRNA and coding genes expression analysis with three chordoma samples
and three fetal nucleus pulposus tissues. lncRNA and gene microarrays were used
to determine the differentially expressed lncRNAs and protein coding genes. 2786
lncRNAs and 3286 coding genes were significantly up-regulated in chordoma, while
2042 lncRNAs and 1006 coding genes were down-regulated. Pearson correlation
analysis was conducted to correlate differentially expressed lncRNAs with protein
coding genes, indicating a comprehensive lncRNA-coding gene co-expression network
in chordoma. Cis-correlation analysis showed that various transcripts of MEG3 and
MEG8 were paired with the most differentially expressed gene DLK1. As located in
the same locus, we further analyzed the miRNA clusters in this region, and
identified that 61.22% of these miRNAs were significantly down-regulated,
implying the silence of the imprinted gene cluster DLK1-MEG3. Overexpression of
MEG3 suppressed the proliferation of chordoma cells. Our study pointed out the
potential role of lncRNAs in chordoma, presented the lncRNA-coding genes co
expression profile, and revealed that imprinted gene cluster DLK1-MEG3
contributes to the pathogenesis of chordoma development.
PMID- 29348852
TI - Reduced FBXW7 expression in pancreatic cancer correlates with poor prognosis and
chemotherapeutic resistance via accumulation of MCL1.
AB - Pancreatic cancer is a highly malignant tumor type with poor outcomes, and
elucidation of the mechanisms involved in cancer progression and therapeutic
resistance is critical. FBXW7 is a key regulator of tumor malignant potential,
and its substrate MCL1 regulates therapeutic resistance in human malignancies.
Therefore, determination of the relevance of FBXW7 expression is critical for
improving patient outcomes. In this study, we investigated the function and
clinical significance of FBXW7 in pancreatic cancer. FBXW7 expression was
evaluated by immunohistochemistry in 122 pancreatic cancer tissues. Reduced FBXW7
expression was significantly associated with advanced venous invasion, high MCL1
expression, enhanced Ki-67 expression, and poor prognosis and was an independent
poor prognostic factor. Among patients who underwent gemcitabine treatment after
surgery, reduced FBXW7 expression was also significantly associated with poor
prognosis. Knockdown of FBXW7 in vitro enhanced cell proliferation, and
migration, and invasion abilities and promoted gemcitabine and nab-paclitaxel
chemoresistance in pancreatic cancer cells. Moreover, FBXW7-knockdown cells
showed accumulation of MCL1, and the enhanced chemoresistance observed in FBXW7
knockdown cells was eliminated by MCL1 suppression. These results suggested that
FBXW7 was associated with cancer progression and mediated sensitivity to
gemcitabine and nab-paclitaxel via MCL1 accumulation in pancreatic cancer. Thus,
the FBXW7/MCL1 axis may be a promising therapeutic tool to overcome refractory
pancreatic cancer.
PMID- 29348853
TI - 3D-cultivation of NSCLC cell lines induce gene expression alterations of key
cancer-associated pathways and mimic in-vivo conditions.
AB - This work evaluated gene expression differences between a hanging-drop 3D NSCLC
model and 2D cell cultures and their in-vivo relevance by comparison to patient
derived data from The Cancer Genome Atlas. Gene expression of 2D and 3D cultures
for Colo699 and A549 were assessed using Affymetrix HuGene 1.0 ST gene chips.
Biostatistical analyses tested for reproducibility, comparability and significant
differences in gene expression profiles between cell lines, experiments and
culture methods. The analyses revealed a high interassay correlation within
specific culture systems proving a high validity. 979 genes were altered in A549
and 1106 in Colo699 cells due to 3D cultivation. The overlap of changed genes
between the cell lines was small (149), but the involved pathways in the reactome
and GO- analyses showed a high overlap with DNA methylation, cell cycle, SIRT1,
PKN1 pathway, DNA repair and oxidative stress as well known cancer-associated
representatives. Additional specific GSEA-analyses revealed changes in
immunologic and endothelial cell proliferation pathways, whereas hypoxic, EMT and
angiogenic pathways were downregulated. Gene enrichment analyses showed 3D
induced gene up-regulations in the cell lines 38 to be represented in in-vivo
samples of NSCLC patients using data of The Cancer Genome Atlas. Thus, our 3D
NSCLC model might provide a tool for early drug development and investigation of
microenvironment-associated mechanisms. However, this work also highlights the
need for further individualization and model adaption to address remaining
challenges.
PMID- 29348854
TI - Acid ceramidase and its inhibitors: a de novo drug target and a new class of
drugs for killing glioblastoma cancer stem cells with high efficiency.
AB - Glioblastoma remains the most common, malignant primary cancer of the central
nervous system with a low life expectancy and an overall survival of less than
1.5 years. The treatment options are limited and there is no cure. Moreover,
almost all patients develop recurrent tumors, which typically are more
aggressive. Therapeutically resistant glioblastoma or glioblastoma stem-like
cells (GSCs) are hypothesized to cause this inevitable recurrence. Identifying
prognostic biomarkers of glioblastoma will potentially advance knowledge about
glioblastoma tumorigenesis and enable discovery of more effective therapies.
Proteomic analysis of more than 600 glioblastoma-specific proteins revealed, for
the first time, that expression of acid ceramidase (ASAH1) is associated with
poor glioblastoma survival. CD133+ GSCs express significantly higher ASAH1
compared to CD133- GSCs and serum-cultured glioblastoma cell lines, such as
U87MG. These findings implicate ASAH1 as a plausible independent prognostic
marker, providing a target for a therapy tailored toward GSCs. We further
demonstrate that ASAH1 inhibition increases cellular ceramide level and induces
apoptosis. Strikingly, U87MG cells, and three different patient-derived
glioblastoma stem-like cancer cell lines were efficiently killed, through
apoptosis, by three different known ASAH1 inhibitors with IC50's ranging from 11
104 MUM. In comparison, the standard glioblastoma chemotherapy agent,
temozolomide, had minimal GSC-targeted effects at comparable or even higher
concentrations (IC50 > 750 MUM against GSCs). ASAH1 is identified as a de novo
glioblastoma drug target, and ASAH1 inhibitors, such as carmofur, are shown to be
highly effective and to specifically target glioblastoma GSCs. Carmofur is an
ASAH1 inhibitor that crosses the blood-brain barrier, a major bottleneck in
glioblastoma treatment. It has been approved in Japan since 1981 for colorectal
cancer therapy. Therefore, it is poised for repurposing and translation to
glioblastoma clinical trials.
PMID- 29348855
TI - Associations between erythropoietin polymorphisms and risk of diabetic
microvascular complications.
AB - We conducted a meta-analysis to evaluate the relationship between erythropoietin
(EPO) polymorphisms and diabetic microvascular complications. We searched the
PubMed, Embase, Cochrane library, Web of Science, Wanfang, and Chinese National
Knowledge Infrastructure databases for appropriate studies. Odds ratios (ORs)
with 95% confidence intervals (CIs) were calculated to evaluate the associations.
Ultimately, eight studies consisting of 2,861 cases and 2,136 controls were
identified and included in our meta-analysis. Results with our genotype model
indicated an association between rs1617640 polymorphisms and diabetic
microvascular complications (TT vs. GG: OR = 1.544, 95% CI = 1.089-2.189, P =
0.015). No clear associations between the rs1617640 and rs507392 polymorphisms
and diabetic retinopathy were observed. By contrast, rs551238 polymorphisms were
associated with increased diabetic retinopathy risk (allele model: OR = 0.774,
95% CI = 0.658-0.911, P = 0.002; genotype model: AC vs. CC: OR = 0.598, 95% CI =
0.402-0.890, P = 0.011; dominant model: OR = 0.561, 95% CI = 0.385-0.817, P =
0.003; recessive model: OR = 0.791, 95% CI = 0.643-0.973, P = 0.026). These
results indicate that EPO polymorphisms are a risk factor for diabetic
microvascular complications.
PMID- 29348856
TI - Prognostic value of diametrically polarized tumor-associated macrophages in
multiple myeloma.
AB - Tumor-associated macrophages (TAMs) are correlated with the prognosis of
different types of solid tumors and lymphoma, according to many clinical studies.
In vitro experiments have demonstrated the roles of these cells in myeloma cell
survival, angiogenesis, immunomodulation, drug resistance, and the interaction
between malignant myeloma cells and the microenvironment. Here, we investigated
the prognostic significance of TAMs in patients with multiple myeloma (MM). We
evaluated the polarized functional status of bone marrow infiltrated by TAMs by
immunohistochemical staining of CD68, iNOS, and CD163 in 240 patients with MM
from January 2009 to December 2014. The overall response rates to chemotherapy
were lower in patients with high CD68+ or CD163+ TAM densities than in those with
low densities. Kaplan-Meier analysis showed that the progression-free survival
(PFS, p = 0.001) and overall survival (OS, p < 0.001) of patients with low CD163+
TAM density were significantly higher than those of patients with high CD163+ TAM
density. Furthermore, combined analysis of iNOS+ and CD163+ TAMs (iNOS/CD163
signature) exhibited greater power in predicting patient outcomes for both PFS (p
< 0.001) and OS (p < 0.001). Moreover, Cox regression analysis identified iNOS+
and CD163+ TAMs as independent prognostic factors (p = 0.007, p < 0.001,
respectively). These factors could be combined with the international staging
system (ISS) to generate a predictive nomogram for patient outcomes. Our findings
suggest that the mosaic of diametrically polarized TAMs is a novel independent
prognostic factor that could be integrated into the evaluation of and therapy for
MM.
PMID- 29348858
TI - The survival benefit of neoadjuvant chemotherapy and pCR among patients with
advanced stage triple negative breast cancer.
AB - Triple negative breast cancer (TNBC) is an aggressive subtype that accounts for
15-20% of cases, with a higher incidence of relapse/death. Even with adjuvant
chemotherapy, the 5 year distant metastasis-free survival rate remains low. A
total of 452 tumor registry patients with TNBC and no evidence of metastatic
disease were identified over the period of 1996-2011. The median age and follow
up time were 51 (range=21-88) and 3.9 (range=0.14-14) years. Approximately 75% of
patients with stage III disease received neoadjuvant chemotherapy (NACT) compared
with 47% for stage II. Patients with stage I disease predominantly received
adjuvant chemotherapy (ACT). Among those who underwent NACT (n=202), 33% had a
pathological complete response (pCR). Overall (OS) and disease-free (DFS)
survival were significantly longer among patients achieving pCR (versus residual
disease) following NACT (OS: all patients P<0.0001, stage II P<0.0001, stage III
P=0.0062; DFS: all patients P<0.0001, stage II P=0.0011, stage III P=0.015). ACT
was not associated with improved OS or DFS for stage III disease. Adjustment for
age, chemotherapy, health insurance type, lymphovascular invasion, race,
radiation, and surgery did not alter our results. These findings suggest that pCR
following NACT is associated with improved survival among patients with TNBC,
independent of diagnostic stage.
PMID- 29348859
TI - The effect of systematic lower-limb rehabilitation training in elderly patients
undergoing lumbar fusion surgery: a retrospective study.
AB - Objectives: The purpose of this study was to explore the effect of systematic
lower-limb rehabilitation training in elderly patients undergoing lumbar fusion
surgery due to serious degenerative intervertebral disc diseases. Results: At the
1st week after surgery, clinical rehabilitation effect in intervention group was
better regarding lower-limb muscle strength, lower-limb DVT, VAS score, and ODI,
as compared with control group (all p < 0.05). During the first two weeks after
surgery, satisfaction rate in intervention group was higher than that in control
group. However, there was no significant difference at last follow-up after
surgery when comparing intervention group to control group. Materials and
Methods: We retrospectively collected medical records of elderly patients (aged
>= 60 yrs) undergoing lumbar fusion surgery between 01/2013 and 01/2015 in our
department. Some of the identified patients randomly underwent postoperative
systematic training of lower-limb rehabilitation gymnastics (intervention group,
n = 240), the others not (control group, n = 300). During postoperative period,
intervention group received lower-limb rehabilitation gymnastics treatment for 3
months, but control group did not. All patients were routinely asked to return
hospital for a check in the 1st postoperative week, as well as the 2nd week, the
1st month, and the 3rd month. Clinical outcomes were evaluated by scoring lower
limb muscle strength, detecting lower-limb deep venous thrombosis (DVT), visual
analogue scale (VAS) score, lumbar JOA score, Oswestry disability index (ODI)
questionnaire, and performing satisfaction survey. Conclusions: In early
postoperative stage, systematic lower-limb rehabilitation training can
effectively speed up the recovery, beneficial to reducing lower-limb DVT and
increasing patient satisfaction rate.
PMID- 29348857
TI - Influenza vaccination might reduce the risk of ischemic stroke in patients with
atrial fibrillation: A population-based cohort study.
AB - Purpose: Atrial fibrillation (AF) is associated with the risk of ischemic stroke,
regardless of the administration of appropriate antithrombotic prophylaxis. This
study investigated whether influenza vaccination is associated with the risk of
ischemic stroke, to determine a solution to reduce this risk in patients with AF.
Methods: We used data from the Taiwan National Health Insurance Research
Database. The study cohort comprised all patients diagnosed as having AF (n = 14
454) before January 1, 2005; these patients were followed until December 31,
2012. The index date was January 1, 2005. A propensity score was derived using a
logistic regression model to estimate the effect of vaccination by accounting for
covariates that predict receiving the intervention (vaccine). A Cox proportional
hazard model was used to calculate the hazard ratios (HRs) of ischemic stroke in
vaccinated and unvaccinated patients with AF. Results: We included 6570 patients
(2547 [38.77%] with and 4023 [61.23%] without influenza vaccination). The
adjusted HRs (aHRs) of ischemic stroke were lower in the vaccinated patients than
in the unvaccinated patients (influenza season, noninfluenza season, and all
seasons: aHRs = 0.59, 0.50, and 0.55; P < 0.001, P < 0.001, and P < 0.001,
respectively). Conclusions: Influenza vaccination might exert a dose-response
effect against ischemic stroke in patients with AF who have risk factors for
ischemic stroke by reducing the incidence of ischemic stroke, particularly in
those aged 65-74 and >=75 y.
PMID- 29348860
TI - Silencing ROR1 and ROR2 inhibits invasion and adhesion in an organotypic model of
ovarian cancer metastasis.
AB - OBJECTIVE: Elevated expression of the ROR1 and ROR2 Wnt receptors has been noted
in both the tumour and stromal compartments of ovarian cancer patient tissue
samples. In vitro studies have suggested these receptors play a role in ovarian
cancer metastasis. However, these previous studies have utilised simple 2D in
vitro models to investigate cancer cell growth and migration, which does not
allow investigation of stromal involvement in Wnt driven metastasis. AIM: To
investigate targeting ROR1 and ROR2 using a primary co-culture 3D model of
epithelial ovarian cancer dissemination to the omentum. METHODS: Primary
fibroblasts (NOF) and mesothelial (HPMC) cells were isolated from fresh samples
of omentum collected from women with benign or non-metastatic conditions and
cultured with collagen to produce a organotypic 3D model. Stable shRNA knockdown
of ROR1, ROR2 and double ROR1/ROR2 in OVCAR4 cells were plated onto the 3D model
to measure adhesion, or using a transwell to measure invasion. Gene expression
changes in primary cells upon OVCAR4 interaction was evaluated using indirect
transwell co-culture. RESULTS: Double knockdown of ROR1 and ROR2 strongly
inhibited cell adhesion (p<0.05) and invasion (P<0.05) to the omentum model. ROR2
was up regulated in primary fibroblasts when cultured with OVCAR4 (P=0.05) and
ectopic overexpression of ROR2 in NOFs inhibited cell proliferation (P<0.01) but
increased cell migration. CONCLUSION: The combination of ROR1 and ROR2 signalling
influences ovarian cancer dissemination to the omentum, however ROR2 may also
play a role in stromal activation during metastasis. Therefore, targeting both
ROR1 and ROR2 may be a powerful approach to treating ovarian cancer.
PMID- 29348861
TI - Primary tumor-associated expression of CXCR4 predicts formation of local and
systemic recurrency in head and neck squamous cell carcinoma.
AB - Objectives: Despite modern treatment regimens, overall survival in head and neck
squamous cell carcinomas (HNSCC) is less than 50% due to local and systemic
disease recurrency. The current study aims to identify molecular markers in
primary tumor specimens that predict the risk for local and systemic recurrency
at the time of initial diagnosis. Methods: The study included clinic-pathological
data of 1,057 HNSCC. MMP2/9, TIMP1/2, CXCR4, and CXCL12 immunohistochemistry was
done in 150 randomly selected specimens. For statistics, we employed Chi square,
Fisher exact, and Student's t-test. Overall survival (OS) was calculated by
Kaplan-Meier and log-rank test. Prognostic variables were subsequently evaluated
by Cox regression for forward selection. Results: CXCR4 positive specimens
demonstrated a significant increased risk for tumor recurrency associated death
(rT: HR 10.07; p=0.001 / rN: HR 5.04; p=0.013 / rM: HR 2.49; p=0.029) when
compared with their unaltered counterparts. Expression of MMP9, TIMP2, CXCR4, and
CXCL12 was significantly increased in distant metastasized patients (p<0.0001)
and showed significant cross-correlation. In addition, CXCR4 positivity was
associated with an increased risk to die due to enhanced T or N status (T1/2 vs.
T3/4: HR 5.78; p=0.017; N0 vs. N+: HR 5.18; p=0.033). Conclusion: CXCR4
positivity in tumor samples at initial diagnosis were associated with reduced
overall survival, in particular with respect to increasing T/N status, local and
systemic recurrency.
PMID- 29348862
TI - Digital gene expression analysis in mice lung with coinfection of influenza and
streptococcus pneumoniae.
AB - Influenza A virus (IAV) and Streptococcus pneumoniae (SP) are two major upper
respiratory tract pathogens that can also cause infection in polarized bronchial
epithelial cells to exacerbate disease in coinfected individuals which may result
in significant morbidity. However, the underlying molecular mechanism is poorly
understood. Here, we employed BALB/c ByJ mice inflected with SP, IAV, IAV
followed by SP (IAV+SP) and PBS (Control) as models to survey the global gene
expression using digital gene expression (DGE) profiling. We attempt to gain
insights into the underlying genetic basis of this synergy at the expression
level. Gene expression profiles were obtain using the Illimina/Hisseq sequencing
technique, and further analyzed by enrichment analysis of Gene Ontology (GO) and
Pathway function. The hematoxylin-eosin (HE) staining revealed different tissue
changes in groups during which IAV+SP group showed the most severe cell
apoptosis. Compared with Control, a total of 2731, 3221 and 3946 differentially
expressed genes (DEGs) were detected in SP, IAV and IAV+SP respectively. Besides,
sixty-two GO terms were identified by Gene Ontology functional enrichment
analysis, such as cell killing, biological regulation, response to stimulus,
signaling, biological adhesion, enzyme regulator activity, receptor regulator
activity and translation regulator activity. Pathway significant enrichment
analysis indicated the dysregulation of multiple pathways, including apoptosis
pathway. Among these, five selected genes were further verified by quantitative
reverse transcription-polymerase chain reaction (qRT-PCR). This study shows that
infection with SP, IAV or IAV+SP induces apoptosis with different degrees which
might provide insights into the molecular mechanisms to facilitate further
research.
PMID- 29348863
TI - No association between TP53 Arg72Pro polymorphism and ovarian cancer risk:
evidence from 10113 subjects.
AB - The TP53 gene product is an important regulator of cell growth and a tumor
suppressor. The association between TP53 Arg72Pro polymorphism and ovarian cancer
risk has been widely investigated, but the results are contradictory. We
therefore searched the PubMed, EMBASE and Chinese Biomedical databases for
studies on the relation between TP53 Arg72Pro polymorphism and ovarian cancer
risk. Our final meta-analysis included 24 published studies with 3271 cases and
6842 controls. Pooled results indicated that there was no significant association
between TP53 Arg72Pro polymorphism and ovarian cancer risk [Pro/Pro vs. Arg/Arg:
odds ratio (OR) =1.04, 95% confidence interval (CI) = 0.81-1.34; Arg/Pro vs.
Arg/Arg: OR = 1.14, 95% CI = 0.96-1.36; recessive: OR = 1.05, 95% CI = 0.90-1.22;
dominant: OR = 1.12, 95% CI = 0.94-1.33; and Pro vs. Arg: OR = 1.06, 95% CI=0.93
1.20]. Likewise, stratified analyses failed to reveal a genetic association.
Despite some limitations, the present meta-analysis provides statistical evidence
indicating a lack of association between TP53 Arg72Pro polymorphism and ovarian
cancer risk.
PMID- 29348864
TI - The macro-evolutionary events in esophageal squamous cell carcinoma.
AB - Understanding the evolutionary processes operative in cancer genome may provide
insights into clinical outcome and drug-resistance. However, studies focus on
genomic signatures, especially for macro-evolutionary events, in esophageal
squamous cell carcinoma (ESCC) are limited. Here, we integrated published genomic
sequencing data to investigate underlying evolutionary characteristics in ESCC.
We found most of ESCC genomes were polyploidy with high genomic instability.
Whole genome doubling that acts as one of mechanisms for polyploidy was predicted
as a late event in the majority of ESCC genome. Moreover, loss of heterozygosity
events were more likely to occur in chromosomes harboring tumor suppressor genes
in ESCC. The 40% of neutral loss of heterozygosity events was not a result of
genome doubling, suggesting an alternative mechanism for neutral loss of
heterozygosity formation. Importantly, deconstruction of copy number alterations
extending to telomere revealed that telomere-bounded copy number alterations play
a critical role for amplification/deletion of oncogenes/suppressor genes. For
well-known genes SOX2, PIK3CA and TERT, nearly all of their amplifications were
telomere bounded, which was further confirmed in a Japanese ESCC cohort.
Furthermore, we provide evidence that karyotype evolution was mostly punctuated
in ESCC. Collectively, our data reveal the potential biological role of whole
genome doubling, neutral loss of heterozygosity and telomere-bounded copy number
alterations, and highlight mecro-evolution in ESCC tumorigenesis.
PMID- 29348865
TI - Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells.
AB - Peripheral T-cell lymphomas (PTCLs) are a group of very aggressive non-Hodgkin's
lymphomas (NHLs) with poor prognoses and account for a majority of T-cell
malignancies. Overall, the standard of care for patients with T-cell malignancies
is poorly established, and there is an urgent clinical need for a new approach.
As demonstrated in B-cell malignancies, chimeric antigen receptor (CAR)
immunotherapy provides great hope as a curative treatment regimen. Because PTCLs
develop from mature T-cells, these NHLs are commonly CD4+, and CD4 is highly and
uniformly expressed. Therefore, CD4 is an ideal target for PTCL CAR
immunotherapy. To that effect, we created a robust third-generation anti-CD4 CAR
construct (CD4CAR) and introduced it into clonal NK cells (NK-92). CD4CAR NK-92
cells specifically and robustly eliminated diverse CD4+ human T-cell leukemia and
lymphoma cell lines (KARPAS-299, CCRF-CEM, and HL60) and patient samples ex vivo.
Furthermore, CD4CAR NK-92 cells effectively targeted KARPAS-299 cells in vivo
that modeled difficult-to-access lymphoma nodules, significantly prolonging
survival. In our study, we present novel targeting of CD4 using CAR-modified NK
cells, and demonstrate efficacy. Combined, our data support CD4CAR NK cell
immunotherapy as a potential new avenue for the treatment of PTCLs and CD4+ T
cell malignancies.
PMID- 29348866
TI - Protein methyltransferases and demethylases dictate CD8+ T-cell exclusion in
squamous cell carcinoma of the head and neck.
AB - A subset of patients with recurrent/metastatic squamous cell carcinoma of the
head and neck (SCCHN) benefit from pembrolizumab and nivolumab, but the majority
of patients do not probably due to lack of activated cytotoxic CD8+ T-cells in
their tumor tissues. Herein, we aim to investigate whether specific protein
methyltransferases (PMTs) and demethylases (PDMTs) could play any roles in the
CD8+ T-cell exclusion process in HPV-negative SCCHN. RNA sequencing data from the
TCGA database were interrogated for HPV-negative SCCHN patients using a 10-gene
chemokine signature that classifies SCCHN tissues into CD8+ T-cell inflamed and
non-CD8+ T-cell inflamed phenotypes. Among 53 PMT/PDMT genes examined in the TCGA
HPV-negative SCCHN database, expression levels of 15 PMT/PDMT genes were
significantly negatively correlated with the chemokine signature score and CD8
mRNA expression levels. The expression level of each of these 15 PMT/PDMT genes
showed significantly negative correlations with immune-active chemokines, as well
as HLA class I and APM molecules. siRNA-mediated knockdown of a candidate PMT,
SMYD3, led to upregulation of CXCL9, CXCL10, CXCL11 and TAP1 at mRNA and protein
levels in HPV-negative SCCHN cell lines. These findings demonstrate that
overexpression of some PMTs and PDMTs seems to be related with the non-CD8+ T
cell inflamed phenotype and may drive CD8+ T-cell exclusion in HPV-negative
SCCHN. This study suggests that chromatin modifiers contribute to CD8+ T-cell
exclusion and antigen presentation capacity of HPV-negative SCCHN, supporting
that targeting of specific PMTs and/or PDMTs could enhance CD8+ T-cell
infiltration and increase the proportion of patients that may benefit from
immunotherapy.
PMID- 29348867
TI - Pleural MAC30 as a prognostic marker in NSCLC with malignant pleural effusion.
AB - Over-expressed meningioma-associate protein (MAC30) in tissues was associated
with malignant tumor differentiation, metastasis and poor prognosis. However, the
attention of MAC30 in pleural effusion from lung tumor is insufficient. Our
retrospective study was prepared to explore the clinical values on diagnosis and
prognosis of MAC30 from malignant pleural effusion (MPE) in non-small cell lung
cancer (NSCLC). Levels of MAC30 were confirmed in MPE from 48 NSCLC patients and
in benign pleural effusion (BPE) from 45 controls via enzyme-linked immunosorbent
assay (ELISA). The association of MAC30 in MPE with clinical significance was
further determined. We found that the levels of MAC30 in MPE were obviously
higher than those in BPE (p < 0.05). Moreover, with a cutoff point (17.5 ng/ml),
we confirmed the sensitivity and specificity of MAC30 for MPE were 82.7% and
85.3% using ROC curve analysis. Indeed, longer overall survival (OS) was present
in NSCLC patients with low MAC30 expression in MPE. Multivariate analysis
explicated that elevated MAC30 in MPE was an independent prognostic factor for
shorter OS of NSCLC. Our data suggests that MAC30 in pleural effusion could be a
potential prognostic marker in NSCLC with MPE.
PMID- 29348868
TI - Luminal-like HER2-negative stage IA breast cancer: a multicenter retrospective
study on long-term outcome with propensity score analysis.
AB - The benefit of adding chemotherapy (CT) to adjuvant hormone therapy (HT) in stage
IA luminal-like HER2-negative breast cancer (BC) is unclear. We retrospectively
evaluated predictive factors and clinical outcome of 1,222 patients from 4
oncologic centers. Three hundred and eighty patients received CT and HT (CT
cohort) and 842 received HT alone (HT-cohort). Disease-free survival (DFS) and
overall survival (OS) were evaluated with univariate and multivariate analyses.
We also applied the propensity score methodology. Compared with the HT-cohort,
patients in the CT-cohort were more likely to be younger, have larger tumors of a
higher histological grade that were Ki67-positive, and lower estrogen and
progesterone receptor expression. At univariate analysis, a higher histological
grade and Ki67 were significantly associated to a lower DFS. At multivariable
analysis, only histological grade was predictive of DFS. The CT-cohort had a
worse outcome than the HT-cohort in terms of DFS and OS, but differences
disappeared when matched according to propensity score. In summary, patients with
stage IA luminal-like BC had an excellent prognosis, however relapse and
mortality were higher in the CT-cohort than in the HT-cohort. Longer use of
adjuvant HT or other therapeutic strategies may be needed to improve outcome.
PMID- 29348869
TI - Role of the N-terminal lid in regulating the interaction of phosphorylated MDMX
with p53.
AB - Murine double minute 4 protein (MDMX) is crucial for the regulation of the tumor
suppressor protein p53. Phosphorylation of the N-terminal domain of MDMX is
thought to affect its binding with the transactivation domain of p53, thus
playing a role in p53 regulation. In this study, the effects of MDMX
phosphorylation on the binding of p53 were investigated using molecular dynamics
simulations. It is shown that in addition to the previously proposed mechanism in
which phosphorylated Y99 of MDMX inhibits p53 binding through steric clash with
P27 of p53, the N-terminal lid of MDMX also appears to play an important role in
regulating the phosphorylation-dependent interactions between MDMX and p53. In
the proposed mechanism, phosphorylated Y99 aids in pulling the lid into the p53
binding pocket, thus inhibiting the binding between MDMX and p53. Rebinding of
p53 appears to be facilitated by the subsequent phosphorylation of Y55, which
draws the lid away from the binding pocket by electrostatic attraction of the
lid's positively charged N-terminus. The ability to target these mechanisms for
the proper regulation of p53 could have important implications for understanding
cancer biology and for drug development.
PMID- 29348870
TI - Nepsilon-carboxymethyl-lysine promotes calcium deposition in VSMCs via
intracellular oxidative stress-induced PDK4 activation and alters glucose
metabolism.
AB - Diabetes and vascular calcification are intrinsically linked. We previously
reported that advanced glycation end products (AGEs) accelerate calcium
deposition in vascular smooth muscle cells (VSMCs) via excessive oxidative
stress. However, the underlying mechanism remains poorly understood. Pyruvate
dehydrogenase kinase 4 (PDK4) is an important mitochondrial matrix enzyme in
cellular energy metabolism. Since hyperactivation of PDK4 has been reported in
calcified vessels and in patients with diabetes mellitus, inhibition of PDK4
expression may be a strategy for the prevention of diabetic vascular
calcification. In this study, we used a rat VSMC model to investigate the role of
PDK4 in diabetic vascular calcification and further explore the underlying
mechanisms. We observed that Nepsilon-carboxymethyl-lysine (CML), which is a
major immunogen of AGEs, accelerated calcium deposition in VSMCs through PDK4
activation. An elevated level of reactive oxygen species (ROS) acted as a signal
transduction intermediate to increase PDK4 expression. Either inhibition of PDK4
expression or RAGE (receptor for AGEs) blockade attenuated CML-induced VSMC
calcification, as shown by decreased alkaline phosphatase (ALP) activity and runt
related transcription factor 2 (RUNX2) expression. Glucose consumption and
lactate production were increased during CML-induced VSMC calcification.
Importantly, CML accelerates glycolysis in VSMCs via a PDK4-dependent pathway. In
conclusion, this study demonstrates a novel mechanism by which CML promotes VSMC
calcification via PDK4 activation and alters glucose metabolism in VSMCs.
PMID- 29348871
TI - Radiation therapy for stage IVA uterine cervical cancer: treatment outcomes
including prognostic factors and risk of vesicovaginal and rectovaginal fistulas.
AB - Purpose: To evaluate the safety and efficacy of radiation therapy for stage IVA
uterine cervical cancer and to identify an optimal radiation regimen. Results:
Seventeen of the 28 patients developed recurrence after radiation therapy (local
recurrence in 10 and distant metastasis in 12). The local control and distant
metastasis-free rates at 3 years in all patients were 61% and 49%, respectively.
Fourteen patients died after radiation therapy, and all but 2 died of tumor
progression. The disease-free, cause-specific, and overall survival rates at 3
years in all patients were 32%, 49%, and 45%, respectively, and the estimated
median survival time was 32 months. Tumor size (P = 0.007) and involvement in the
lower third of vagina (P = 0.006) were significant prognostic factors for local
control. Older age (P = 0.018) and performance status (P = 0.020) were
significant prognostic factors for distant metastasis. The presence of
hydronephrosis was the sole significant prognostic factor for survival (P =
0.026). Only 2 patients developed grade 3 late toxicities (vesicovaginal fistula
and radiation proctitis, respectively). Materials and Methods: Twenty-eight
patients with stage IVA uterine cervical cancer received radiation therapy. All
patients initially received external pelvic irradiation at a median dose of 50.4
Gy in 28 fractions. Twenty patients also received high-dose-rate intracavitary
brachytherapy at a median dose of 22 Gy in 4 fractions. These fraction sizes were
lower than conventional sizes. The total median dose for all 28 patients was 68.7
Gy. Conclusions: Radiation therapy is safe and effective for treatment of stage
IVA uterine cervical cancer. The reduced radiation dose per fraction may
contribute to the prevention of vesicovaginal fistula formation.
PMID- 29348872
TI - Gene expression profiling reveals U1 snRNA regulates cancer gene expression.
AB - U1 small nuclear RNA (U1 snRNA), as one of the most abundant ncRNAs in human
cells, plays an important role in splicing of pre-mRNAs. Compared to previous
studies which have focused on the primary function of U1 snRNA and the
neurodegenerative diseases caused by abnormalities of U1 snRNA, this study is to
investigate how U1 snRNA over-expression affects the expression of mammal genes
on a genome-wide scale. By comparing the gene expression profiles of U1 snRNA
over-expressed cells with those of their controls using microarray experiments,
916 genes or loci were identified significantly Differentially Expressed (DE).
These 595 up-regulated DE genes and 321 down-regulated DE genes were analyzed
using annotations from GO categories and pathways from the KEGG database. As a
result, three of 12 enriched pathways were well-known cancer pathways, while the
other nine pathways were associated to cancers in previous studies. The further
analysis of 73 genes involved in 12 pathways suggested that U1 snRNA could
regulate cancer gene expression. The microarray data under the GEO Series
accession number GSE84304 is available in the NCBI GEO database.
PMID- 29348873
TI - Impaired epidermal Langerhans cell maturation in TGFbeta-inducible early gene 1
(TIEG1) knockout mice.
AB - TGF-beta-inducible early gene 1 (TIEG1), also known as Kruppel-like factor 10
(Klf10), represents a major downstream transcription factor of transforming
growth factor-beta1 (TGF-beta1) signaling. Epidermal Langerhans cells (LCs), a
unique subpopulation of dendritic cells (DC), essentially mediates immune
surveillance and tolerance. TGF-beta1 plays a pivotal role in LC maintenance and
function after birth, although the underpinning mechanisms remain elusive. Here,
we hypothesized that TIEG1 might be involved in TGF-beta1-mediated LC homeostasis
and function. Utilizing TIEG1 null mice, we discovered that TIEG1 deficiency did
not alter LC homeostasis at the steady state and LC repopulation at inflamed
state, as well as their antigen-uptake capacity, but significantly impaired their
maturation ability, which was opposite to the fact that loss of TGF-beta1 induced
spontaneous LC maturation. Moreover, the ablation of TIEG1 enhanced skin contact
hypersensitivity response. Our results suggested that TIEG1 is not a key molecule
involved in TGF-beta1-mediated homeostasis, while TIEG1-related signaling
pathways regulate LC maturation and their function.
PMID- 29348874
TI - Value of CT-MRI fusion in iodine-125 brachytherapy for high-grade glioma.
AB - Purposes: To develop a fast, accurate and robust method of fusing Computed
Tomography (CT) with pre-operative Magnetic Resonance Imaging (MRI) and evaluate
the impact of using the fused data on the implantation of Iodine-125 (125I) seeds
for brachytherapy of high-grade gliomas (HGG). Methods: A study was performed on
a cohort of 10 consecutive patients with HGG were treated by 125I brachytherapy
with CT-MRI fusion image guided (CMGB), and 10 patients treated with CT alone
guided (CGB). Statistical analysis was performed to compare (1) the planning
target volume, (2) the accuracy of location of catheters, (3) the target volume
covered by 150% prescribe dose (V150), (4) the target volume covered by 200%
prescribe dose (V200), and (5) the conformity index (CI) with or without fused
data. Results: The median planning target volume was 50.1 cm3 in CGB, and 56.25
cm3 in CMGB with significant difference (p = 0.005). The accuracy of catheter
insertion was 94.4% with CMGB and 78.9% with CGB. The median V150 and V200 was
45.32% vs 64.24% and 32.81% vs 53.17% in CGB and CMGB, respectively. There was
significant difference for CI (83.5% vs. 74.5%, p < 0.05) in the two groups for
the post-operative verification. Conclusions: The proposed MRI-CT fusion method
enables a quantitative assessment of impact on HGG brachytherapy. The additional
information obtained from the fused images can be utilized for more accurate
delineation of lesion boundaries and targeting of catheters. Experimental results
show that the fusion algorithm is robust and reliable in clinical practice.
PMID- 29348875
TI - Radiosensitization of the PI3K inhibitor HS-173 through reduction of DNA damage
repair in pancreatic cancer.
AB - Activation of PI3K/AKT pathway occurs frequently in tumors and is correlated with
radioresistance. The PI3K/AKT pathway can be an important target for improvement
of radiotherapy. Although adding of chemotherapy to radiation therapy regimen
enhances survival in patients with locally advanced pancreatic cancer, more
effective therapies for increasing radiosensitivity are urgently needed. In this
study, we investigated whether the novel PI3K inhibitor HS-173 could attenuate
radiation-induced up-regulation of DNA damage repair processes and assessed its
efficacy as a radio- and chemo-sensitizer. Radiosensitizing effects of HS-173
were tested in human pancreatic cells using clonogenic survival and growth
assays. Mechanisms underlying the effects of HS-173 and radiation were determined
by assessing cell cycle and DNA damage- repair pathway components, including
ataxia-telangiectasia mutated (ATM) and DNA-dependent protein kinase catalytic
subunit (DNA-PKcs). The in vivo efficacy of HS-173 in cancer radiotherapy was
evaluated using a human tumor xenograft model. HS-173 significantly increased the
sensitivity of pancreatic cancer cells to radiation, an effect that was
associated with G2/M cell cycle arrest. HS-173 also significantly attenuated DNA
damage repair by potently inhibiting ATM and DNA-PKcs, the two major kinases that
respond to radiation-induced DNA double-strand breaks (DSBs), resulting in
sustained DNA damage. Moreover, the combination of HS-173 and radiation delayed
tumor growth and impaired DNA repair in a pancreatic cancer xenograft model,
reflecting enhanced radiosensitization. These results showed that HS-173
significantly improved radiotherapy by inhibiting the DNA damage-repair pathway
in pancreatic cancer. We therefore suggest that HS-173 may be an effective
radiosensitizer for pancreatic cancer.
PMID- 29348876
TI - Genome-wide transcriptional profiling identifies potential signatures in
discriminating active tuberculosis from latent infection.
AB - To better understand the host immune response involved in the progression from
latent tuberculosis infection (LTBI) to active tuberculosis (TB) and identify the
potential signatures for discriminating TB from LTBI, we performed a genome-wide
transcriptional profile of Mycobacterium tuberculosis (M.TB)-specific antigens
stimulated peripheral blood mononuclear cells (PBMCs) from patients with TB, LTBI
individuals and healthy controls (HCs). A total of 209 and 234 differentially
expressed genes were detected in TB vs. LTBI and TB vs. HCs, respectively.
Nineteen differentially expressed genes with top fold change between TB and the
other 2 groups were validated using quantitative real-time PCR (qPCR), and showed
94.7% consistent expression pattern with microarray test. Six genes were selected
for further validation in an independent sample set of 230 samples. Expression of
the resistin (RETN) and kallikrein 1 (KLK1) genes showed the greatest difference
between the TB and LTBI or HC groups (P < 0.0001). Receiver operating
characteristic curve (ROC) analysis showed that the areas under the curve (AUC)
for RETN and KLK1 were 0.844 (0.783-0.904) and 0.833 (0.769-0.897), respectively,
when discriminating TB from LTBI. The combination of these two genes achieved the
best discriminative capacity [AUC = 0.916 (0.872-0.961)], with a sensitivity of
71.2% (58.7%-81.7%) and a specificity of 93.6% (85.7%-97.9%). Our results provide
a new potentially diagnostic signature for discriminating TB and LTBI and have
important implications for better understanding the pathogenesis involved in the
transition from latent infection to TB activation.
PMID- 29348877
TI - Role of IRF4 in resistance to immunomodulatory (IMid) compounds(r) in
Waldenstrom's macroglobulinemia.
AB - Background: Immunomodulatory drugs, IMid compounds, are active in Waldenstrom's
macroglobulinemia (WM), although in a lesser extent than multiple myeloma, where
it was initially developed. We hypothesized WM tumour cells might develop
mechanisms of resistance, and sought to identify and describe these mechanisms.
Material and Method: MM and WM-derived cell lines, and Waldenstrom's CD19+ cells
were treated using both lenalidomide and pomalidomide. Stable CRBN expressing
cells were generated. Results: WM-derived cells were resistant to IMid compounds.
We demonstrated a modulation of the downstream targets of IRF4, despite low
expression of cereblon, and hypothesized IRF4 was the cause for resistance to
IMid compounds. We ruled out the role of various IRF4 regulatory mechanisms, and
other pathways activating WM tumor cells, such as B cell activators. Conclusion:
This study demonstrated that mechanisms of resistance to IMid compounds could be
not related to cereblon. IRF4 was identified as the potential mechanism of
resistance to lenalidomide and pomalidomide in WM. It potentially explains the
lesser activity observed in the clinic in WM. Interestingly, some WM patients
benefited strongly to lenalidomide and pomalidomide, and future studies will have
to describe the indirect mechanisms of IMid compounds in WM, possibly related to
an immune-mediated process.
PMID- 29348878
TI - Identification of cancer prognosis-associated functional modules using
differential co-expression networks.
AB - The rapid accumulation of cancer-related data owing to high-throughput
technologies has provided unprecedented choices to understand the progression of
cancer and discover functional networks in multiple cancers. Establishment of co
expression networks will help us to discover the systemic properties of
carcinogenesis features and regulatory mechanisms of multiple cancers. Here, we
proposed a computational workflow to identify differentially co-expressed gene
modules across 8 cancer types by using combined gene differential expression
analysis methods and a higher-order generalized singular value decomposition.
Four co-expression modules were identified; and oncogenes and tumor suppressors
were significantly enriched in these modules. Functional enrichment analysis
demonstrated the significantly enriched pathways in these modules, including ECM
receptor interaction, focal adhesion and PI3K-Akt signaling pathway. The top
ranked miRNAs (mir-199, mir-29, mir-200) and transcription factors (FOXO4, E2A,
NFAT, and MAZ) were identified, which play an important role in deregulating
cellular energetics; and regulating angiogenesis and cancer immune system. The
clinical significance of the co-expressed gene clusters was assessed by
evaluating their predictability of cancer patients' survival. The predictive
power of different clusters and subclusters was demonstrated. Our results will be
valuable in cancer-related gene function annotation and for the evaluation of
cancer patients' prognosis.
PMID- 29348879
TI - Loss of NEIL3 DNA glycosylase markedly increases replication associated double
strand breaks and enhances sensitivity to ATR inhibitor in glioblastoma cells.
AB - DNA endonuclease eight-like glycosylase 3 (NEIL3) is one of the DNA glycosylases
that removes oxidized DNA base lesions from single-stranded DNA (ssDNA) and non-B
DNA structures. Approximately seven percent of human tumors have an altered NEIL3
gene. However, the role of NEIL3 in replication-associated repair and its impact
on modulating treatment response is not known. Here, we report that NEIL3 is
localized at the DNA double-strand break (DSB) sites during oxidative DNA damage
and replication stress. Loss of NEIL3 significantly increased spontaneous
replication-associated DSBs and recruitment of replication protein A (RPA). In
contrast, we observed a marked decrease in Rad51 on nascent DNA strands at the
replication fork, suggesting that HR-dependent repair is compromised in NEIL3
deficient cells. Interestingly, NEIL3-deficient cells were sensitive to ataxia
telangiectasia and Rad3 related protein (ATR) inhibitor alone or in combination
with PARP1 inhibitor. This study elucidates the mechanism by which NEIL3 is
critical to overcome oxidative and replication-associated genotoxic stress. Our
findings may have important clinical implications to utilize ATR and PARP1
inhibitors to enhance cytotoxicity in tumors that carry altered levels of NEIL3.
PMID- 29348880
TI - The potential mechanism of extracellular high mobility group box-1 protein
mediated p53 expression in immune dysfunction of T lymphocytes.
AB - In the present study, we examined the activity of p53 protein in Jurkat cells
treated with high mobility group box-1 protein (HMGB1), thereafter we
investigated the mechanism of extracellular HMGB1 mediated p53 expression in
immune dysfunction of T lymphocytes. mRNA expression of p53, mdm2, and p21 was
determined by Real-time reverse transcription-polymerase chain reaction(RT-PCR).
The apoptotic rate of Jurkat cells was analyzed by flow cytometry. Expressions of
bcl-2, bax, caspase-3, phosphorylated (p) extracellular signal-regulated kinase
(ERK)1/2, ERK1/2, p-p38 mitogen-activated protein kinase (MAPK), p38 MAPK, and p
c-jun amino-terminal kinase (JNK)1/2 and JNK1/2 were simultaneously determined by
Western blotting. After treatment with HMGB1 (100 ng/ml or 1000 ng/ml), the
proliferative activity of Jurkat cells was significantly decreased, and a low and
medium concentration of HMGB1 induced an up-regulation of p53 mRNA, p-p53 and p53
protein expression. Meanwhile, levels of mdm2 and p21 were elevated by incubated
with HMGB1 (100 ng/ml) for 24 or 48 hours. Moreover, the proliferation of Jurkat
cells in response to HMGB1 (100 ng/ml) in the vector group was significantly
depressed. The bax and caspase-3 levels in p53 shRNA-expressed cells treated with
HMGB1 (100 ng/ml) was markedly decreased, whereas expression of bcl-2 was
obviously enhanced. Among ERK1/2, p38 MAPK and JNK1/2 signaling, only p38 MAPK
pathway could be significantly activated by treatment with HMGB1, and the
specific inhibitor of p38 MAPK was used, p53 and p-p53 expression induced by
HMGB1 were significantly down-regulated. Taken together, our data strongly
indicated that HMGB1 might enhance p53 expression, which was associated with both
the proliferative activity as well as apoptosis of T cells.
PMID- 29348881
TI - Allogeneic stem cell transplantation in acute lymphoblastic leukemia patients
older than 60 years: a survey from the acute leukemia working party of EBMT.
AB - Hematopoietic stem cell transplantation (HSCT) is being increasingly explored as
a treatment modality for older patients with acute lymphoblastic leukemia (ALL).
Yet, concerns regarding the long term outcome of transplantation in older
patients limit the wide spread applicability of this approach. In this analysis
we set out to determine the outcome of ALL patients over the age of 60 who
underwent reduced intensity HSCT. Herein, we present the experience of the acute
leukemia working party (ALWP) of the EBMT in this age group. We analyzed a cohort
of 142 patients transplanted in first remission with a median age of 62 (range 60
76 years) and a median follow-up period of 36 months post-transplant. At 3 years,
overall survival (OS) and leukemia-free survival were 42% and 35%, respectively.
Multivariate analyses identified cytomegalovirus (CMV) donor-recipient matching
(CMV D+/R+) to be significantly associated with inferior OS. Patients
transplanted from unrelated donors experienced increased grade II-IV acute graft
versus host disease compared to those receiving grafts from matched related
donors [Hazard ratio (HR) of 3.7, 95% confidence interval (CI), 1.75-7.8; p =
0.0005). Outcome was not impacted by Philadelphia chromosome status. A select
subset of older ALL patients will benefit from extended survival and a disease
free state following HSCT.
PMID- 29348882
TI - MicroRNA203a suppresses glioma tumorigenesis through an ATM-dependent interferon
response pathway.
AB - Glioblastoma (GBM) is a deadly and incurable brain tumor. Although microRNAs
(miRNAs) play critical roles in regulating the cancer cell phenotype, the
underlying mechanisms of how they regulate tumorigenesis are incompletely
understood. We previously showed that miR-203a is expressed at relatively low
levels in GBM patients, and ectopic miR-203a expression in GBM cell lines
inhibited cell proliferation and migration, increased sensitivity to apoptosis
induced by interferon (IFN) or temozolomide in vitro, and inhibited GBM
tumorigenesis in vivo. Here we show that ectopic expression of miR-203a in GBM
cell lines promotes the IFN response pathway as evidenced by increased IFN
production and IFN-stimulated gene (ISG) expression, and high basal tyrosine
phosphorylation of multiple STAT proteins. Importantly, we identified that miR
203a directly suppressed the protein levels of ataxia-telangiectasia mutated
(ATM) kinase that negatively regulates IFN production. We found that high ATM
expression in GBM correlates with poor patient survival and that ATM expression
is inversely correlated with miR-203a expression. Knockout of ATM expression and
inhibition of ATM function in GBM cell lines inhibited cell proliferation and
migration, increased sensitivity to apoptosis induced by therapeutic agents in
vitro, and markedly suppressed GBM tumor growth and promoted animal survival. In
contrast, restoring ATM levels in GBM cells ectopically expressing miR-203a
increased tumorigenicity and decreased animal survival. Our study suggests that
low miR-203a expression in GBM suppresses the interferon response through an ATM
dependent pathway.
PMID- 29348883
TI - Spatial habitats from multiparametric MR imaging are associated with signaling
pathway activities and survival in glioblastoma.
AB - Glioblastoma (GBM) show significant inter- and intra-tumoral heterogeneity,
impacting response to treatment and overall survival time of 12-15 months. To
study glioblastoma phenotypic heterogeneity, multi-parametric magnetic resonance
images (MRI) of 85 glioblastoma patients from The Cancer Genome Atlas were
analyzed to characterize tumor-derived spatial habitats for their relationship
with outcome (overall survival) and to identify their molecular correlates (i.e.,
determine associated tumor signaling pathways correlated with imaging-derived
habitat measurements). Tumor sub-regions based on four sequences (fluid
attenuated inversion recovery, T1-weighted, post-contrast T1-weighted, and T2
weighted) were defined by automated segmentation. From relative intensity of
pixels in the 3-dimensional tumor region, "imaging habitats" were identified and
analyzed for their association to clinical and genetic data using survival
modeling and Dirichlet regression, respectively. Sixteen distinct tumor sub
regions ("spatial imaging habitats") were derived, and those associated with
overall survival (denoted "relevant" habitats) in glioblastoma patients were
identified. Dirichlet regression implicated each relevant habitat with unique
pathway alterations. Relevant habitats also had some pathways and cellular
processes in common, including phosphorylation of STAT-1 and natural killer cell
activity, consistent with cancer hallmarks. This work revealed clinical relevance
of MRI-derived spatial habitats and their relationship with oncogenic molecular
mechanisms in patients with GBM. Characterizing the associations between imaging
derived phenotypic measurements with the genomic and molecular characteristics of
tumors can enable insights into tumor biology, further enabling the practice of
personalized cancer treatment. The analytical framework and workflow demonstrated
in this study are inherently scalable to multiple MR sequences.
PMID- 29348884
TI - Alpha-1-antitrypsin functions as a protective factor in preeclampsia through
activating Smad2 and inhibitor of DNA binding 4.
AB - Pre-eclampsia (PE) is one of the most common reason for high morbidity and
mortality of maternal and prenatal infants. Production from oxidative stress
results in maternal ROS system and anti-oxidation defense system imbalance to
promote tissue ischemia and hypoxia, and ultimately impairs the maternal organs
and placenta. Our previous study showed that exogenous Alpha-1-antitrypsin (AAT)
and overexpression of AAT in umbilical vein cell (HUVEC) hypoxia-reoxygenation
model could increase the activity of antioxidant enzymes, and played a protective
role in preeclampsia animal model. In this study, we aim to investigate the
underlying mechanism by which AAT prevents PE progress. Whole-exome sequencing
was performed to screen the genes altered by AAT. We found that AAT knockdown
altered the expression of Smad family and Id family genes, and further
demonstrated that AAT positively regulated Id4 expression through activating
Smad2. Reduced Id4 expression and Smad2 phosphorylation were observed in
preeclampsia animal model, which was also confirmed in human placenta tissues. In
addition, AAT protected HUVEC cells from hypoxia/reoxygenation injury and
relieved preeclampsia symptoms through Smad2/Id4 axis. Our data illustrate
AAT/Smad2/Id4 axis is an important mediator of placenta and vascular function
during pregnancy. These findings provide insights into events governing pregnancy
associated disorders, such as preeclampsia.
PMID- 29348885
TI - Drug-resistance in doxorubicin-resistant FL5.12 hematopoietic cells: elevated
MDR1, drug efflux and side-population positive and decreased BCL2-family member
expression.
AB - Chemotherapeutic drug treatment can result in the emergence of drug-resistant
cells. By culturing an interleukin-3 (IL-3)-dependent cell line, FL5.12 cells in
the presence of the chemotherapeutic drug doxorubicin, we isolated FL/Doxo cells
which are multi-drug resistant. Increased levels of drug efflux were detected in
FL/Doxo cells which could be inhibited by the MDR1 inhibitor verapamil but not by
the MRP1 inhibitor MK571. The effects of TP53 and MEK1 were examined by infection
of FL/Doxo cells with retroviruses encoding either a dominant negative TP-53 gene
(FL/Doxo+ TP53 (DN) or a constitutively-activated MEK-1 gene (FL/Doxo + MEK1
(CA). Elevated MDR1 but not MRP1 mRNA transcripts were detected by quantitative
RT-PCR in the drug-resistant cells while transcripts encoding anti-apoptotic
genes such as: BCL2, BCLXL and MCL1 were observed at higher levels in the drug
sensitive FL5.12 cells. The percentage of cells that were side-population
positive was increased in the drug-resistant cells compared to the parental line.
Drug-resistance and side-positive population cells have been associated with
cancer stem cells (CSC). Our studies suggest mechanisms which could allow the
targeting of these molecules to prevent drug-resistance.
PMID- 29348886
TI - FRK inhibits breast cancer cell migration and invasion by suppressing epithelial
mesenchymal transition.
AB - The human fyn-related kinase (FRK) is a non-receptor tyrosine kinase known to
have tumor suppressor activity in breast cancer cells. However, its mechanism of
action has not been fully characterized. We generated FRK-stable MDA-MB-231
breast cancer cell lines and analyzed the effect on cell proliferation,
migration, and invasiveness. We also used kinome analysis to identify potential
FRK-regulated signaling pathways. We employed both immunoblotting and RT-PCR to
identify/validate FRK-regulated targets (proteins and genes) in these cells.
Finally, we interrogated the TCGA and GENT gene expression databases to determine
the correlation between the expression of FRK and epithelial/mesenchymal markers.
We observed that FRK overexpression suppressed cell proliferation, migration, and
invasiveness, inhibited various JAK/STAT, MAPK and Akt signaling pathways, and
suppressed the expression of some STAT3 target genes. Also, FRK overexpression
increased the expression of epithelial markers including E-cadherin mRNA and down
regulated the transcript levels of vimentin, fibronectin, and slug. Finally, we
observed an inverse correlation between FRK expression and mesenchymal markers in
a large cohort of breast cancer cells. Our data, therefore, suggests that FRK
represses cell proliferation, migration and invasiveness by suppressing
epithelial to mesenchymal transition.
PMID- 29348887
TI - RNA-seq expression profiling of rat MCAO model following reperfusion Orexin-A.
AB - Orexin-A is a neuropeptide with potent neuroprotective activity towards cerebral
ischemia-reperfusion (I/R) injury, but few studies have attempted to elucidate
the mechanism. Herein, we performed global gene expression profiling of the
hippocampus following reperfusion with Orexin-A using RNA sequencing (RNA-seq).
RNA-seq identified 649 differentially expressed genes (DEGs) in the Orexin-A
group compared with saline controls (I/R group), of which 149 were up-regulated
and 500 were down-regulated. DEGs were confirmed using qRT-PCR, their molecular
functions, biological processes and molecular components were explored using Gene
Ontology (GO) analysis and 206 KEGG pathways were associated with Orexin-A
treatment. MAPK, chemokine and calcium signalling pathways were mainly
responsible for the neuroprotective effects of Orexin-A. Hspb1, Igf2 and Ptk2b
were selected for functional interaction analysis by GeneMANIA. The results
suggest that Orexin-A modifies gene expression in the hippocampus, leading to
neuroprotection from I/R injury. The study provides a basis for future
elucidation of the molecular mechanisms underlying Orexin-A.
PMID- 29348888
TI - The association analysis of TLR2 and TLR4 gene with tuberculosis in the Tibetan
Chinese population.
AB - Background: The present study was undertaken to explore the relationship of Toll
like receptor (TLR) 2, TLR4 genes polymorphisms with Pulmonary tuberculosis (PTB)
risk in a sample of Chinese population. Methods: For this study, we recruited 467
subjects with PTB and 504 healthy subjects from a Tibetan population living in
near or in Xi'an, China. Association analyses of single-nucleotide polymorphisms
(SNPs) in TLR2 and TLR4 were performed with SPSS Statistics (version 17.0),
SNPStats, Haploview (version 4.2), and SHEsis software. Results: The research
results that is association analysis of pulmonary tuberculosis show there are two
increased-risk SNPs (rs7696323, OR=1.32, 95%CI =1.08-1.62, P= 0.007; rs12377632,
OR=1.30, 95%CI =1.09-1.55, P= 0.004) and three decreased-risk SNPs (rs3804099,
OR=0.64, 95%CI =0.52-0.79, P= 1.9510-5; rs3804100, OR=0.67, 95%CI =0.54-0.82, P=
0.0001; rs11536889, OR=0.54, 95%CI =0.42-0.69, P= 9.1410-7). Conclusions: We
found that two SNPs are associated with increased PTB risk and three SNPs
decreased PTB risk in the Chinese Tibetan population. Our findings demonstrate an
association between TLR2 and TLR4 polymorphisms and PTB.
PMID- 29348889
TI - Metformin and temozolomide, a synergic option to overcome resistance in
glioblastoma multiforme models.
AB - Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with
poor survival. Cytoreduction in association with radiotherapy and temozolomide
(TMZ) is the standard therapy, but response is heterogeneous and life expectancy
is limited. The combined use of chemotherapeutic agents with drugs targeting cell
metabolism is becoming an interesting therapeutic option for cancer treatment.
Here, we found that metformin (MET) enhances TMZ effect on TMZ-sensitive cell
line (U251) and overcomes TMZ-resistance in T98G GBM cell line. In particular,
combined-treatment modulated apoptosis by increasing Bax/Bcl-2 ratio, and reduced
Reactive Oxygen Species (ROS) production. We also observed that MET associated
with TMZ was able to reduce the expression of glioma stem cells (GSC) marker CD90
particularly in T98G cells but not that of CD133. In vivo experiments showed that
combined treatment with TMZ and MET significantly slowed down growth of TMZ
resistant tumors but did not affect overall survival of TMZ-sensitive tumor
bearing mice. In conclusion, our results showed that metformin is able to enhance
TMZ effect in TMZ-resistant cell line suggesting its potential use in TMZ
refractory GBM patients. However, the lack of effect on a GBM malignancy marker
like CD133 requires further evaluation since it might influence response
duration.
PMID- 29348890
TI - Adoptive immunotherapy shows encouraging benefit on non-small cell lung cancer: a
systematic review and meta-analysis.
AB - Although adoptive immunotherapy (AIT) is a novel emerging target treatment for
non-small cell lung cancer (NSCLC), its actual efficacy remains controversial. In
this meta-analysis, we aimed to evaluate the efficacy of AIT for NSCLC. We
systematically searched PubMed, the Cochrane Library, EMBASE, Medline, and Web of
Science for relevant parallel randomized controlled trials (RCTs) and high
quality observation studies of AIT without any language restrictions. Two
investigators reviewed all the texts and extracted information regarding overall
survival rate (OS), progression-free survival rate (PFS), objective response rate
(ORR), and disease control rate (DCR) from eligible studies; sensitivity analyses
and subgroup analyses were also conducted to reduce heterogeneity Of 319 suitable
studies, 15 studies (13 RCTs and 2 observation studies) involving 1684 patients
were finally included. Compared to the Control therapy (CT) group, the AIT group
exhibited better 1-year OS (P = 0.001), 2-year OS (P < 0.001), 3-year OS (P <
0.001), 5-year OS (P = 0.032), 1-year PFS (P < 0.001), and 2-year PFS (P =
0.029). The difference in the ORR (P = 0.293) and DCR (P = 0.123) was not
significant between the groups. The subgroup analysis showed that DC/CIK did more
benefit to NSCLC patients than LAK and the cycles not associated with AIT
efficacy. AIT can significantly improve the OS and PFS with acceptable toxicity
for NSCLC. Nevertheless, further multicenter studies are needed to confirm our
conclusion and determine which adoptive immunotherapy is associated with the
greatest efficacy.
PMID- 29348891
TI - Clinicopathological impacts of high c-Met expression in head and neck squamous
cell carcinoma: a meta-analysis and review.
AB - High c-Met expression has been observed in head and neck squamous cell carcinoma
(HNSCC). However, its clinicopathological impact remains controversial. We
performed this meta-analysis to evaluate the pathologic and prognostic impacts of
c-Met overexpression in patients with HNSCC. A systematic computerized search of
the electronic databases was carried out. From 16 studies, 1,948 patients with
HNSCC were included in the meta-analysis. Compared with HNSCCs showing low c-Met
expression, tumors with high c-Met expression were significantly associated with
higher rate of lymph node metastasis (odds ratio = 3.26, 95% CI: 2.27-4.69, P <
0.00001) and higher T stage (odds ratio = 1.33, 95% CI: 1.03-1.71, P = 0.03). In
addition, patients with c-Met-high HNSCC showed significantly worse disease-free
survival (hazard ratio = 1.49, 95% CI: 1.04-2.14, P = 0.03) and overall survival
(hazard ratio = 1.83, 95% CI: 1.29-2.60, P = 0.0007) than those with c-Met-low
tumor. In conclusion, this meta-analysis demonstrates that high c-Met expression
is significantly associated with worse pathological features and prognosis,
indicating c-Met overexpression is an adverse prognostic marker for patients with
HNSCC.
PMID- 29348892
TI - Association between cadmium exposure and diabetes mellitus risk: a prisma
compliant systematic review and meta-analysis.
AB - Cadmium (Cd) is a pollutant with multiple adverse health effects: cancer, renal
dysfunction, osteoporosis and fracture, and cardiovascular disease. Several
population-based studies found an association between Cd and diabetes mellitus
(DM), but this association is inconsistent with other research. We conducted meta
analysis to examine relationship between urinary/blood Cd exposure and DM risk.
Pertinent studies were identified by searching PubMed and Embase databases, and
combined odds ratio (OR) and corresponding 95% confidence interval (CI) were
applied to evaluate said association. Meta-analysis showed that high U-Cd
exposure is not correlated with DM risk (OR = 1.19; 95% CI = 0.83-1.71), and high
B-Cd exposure is also not associated with increased risk of DM (OR = 1.16; 95% CI
= 0.84-1.62) in the general population. Subgroup and sensitivity analysis proved
similar results, with little evidence of publication bias. This meta-analysis
suggests that high U-Cd/B-Cd exposure may not be risk factor for DM in general
populations. However, large prospective studies are needed to confirm this
finding.
PMID- 29348893
TI - Diagnostic accuracy of DNA methylation in detection of gastric cancer: a meta
analysis.
AB - Emerging studies demonstrate the diagnostic utility of DNA methylation-based
blood test for gastric cancer. The aim of the meta-analysis is to evaluate the
accuracy of blood DNA methylation markers for detecting patients with gastric
cancer. A systematic literature search to November 2016 that evaluated DNA
methylation markers utilizing blood specimen to detect gastric cancer were
selected to derive pooled sensitivities and specificities. 32 studies including
4,172 patients (gastric cancer (N = 2,098), control (N = 2,074)) met the study
criteria. Overall sensitivity of DNA methylation-based blood test for detecting
gastric cancer was 57% (95% CI 50-63%); specificity was 97% (95% CI 95-98%).
Among patients who received plasma-based testing, sensitivity was 71% (95% CI 59
81%); specificity was 89% (95% CI 78-94%). Among patients who received serum
based testing, sensitivity was 50% (95% CI 43-58%); specificity was 98% (95% CI
96-99%). Using multiple methylated genes had sensitivity of 76% (95% CI 64-84%);
specificity of 85% (95% CI 65-95%). DNA methylation test had sensitivity of 55%
(95% CI 47-64%) and specificity of 96% (95% CI 92-98%) for detecting TNM stage
I+II gastric cancer. In conclusion, blood-based DNA methylation test had high
specificity but modest sensitivity for detecting gastric cancer. Evaluating
multiple methylated genes or using plasma sample may improve the diagnostic
sensitivity.
PMID- 29348894
TI - The efficacy and safety of tivantinib in the treatment of solid tumors: a
systematic review and meta-analysis.
AB - Background: Tivantinib was designed to kill cancers by targeting the mesenchymal
epithelial transition (MET) protein. Although numerous tivantinib clinical trials
are ongoing, tivantinib's efficacy and safety are still not clear. This meta
analysis was done to evaluate tivantinib's efficacy and safety in solid tumor
treatment. Materials and Methods: PUBMED, EMBASE, and other databases were
searched for eligible tivantinib clinical trials. The hazard ratio (HR) and 95%
confidence interval (CI) of progression-free and overall survival (PFS and OS,
respectively) were pooled and analyzed to evaluate tivantinib's efficacy. Data
concerning adverse events (Grade >= 3) were pooled to calculate relative risks
(RRs) with 95% CI for tivantinib-treated compared with control arms. Findings:
Patients (1824) from six randomized control trials (RCTs) were enrolled. Compared
with controls, tivantinib produced a significant improvement in PFS (HR, 0.73;
95% CI 0.65-0.83) but not in OS. In the non-small-cell lung cancer (NSCLC)
subgroup, tivantinib combined with erlotinib prolonged patients' PFS when
compared with controls (HR, 0.75; 95% CI, 0.65-0.86). In the white population,
tivantinib also significantly improve PFS between treatment and control arms (HR,
0.75; 95% CI, 0.65-0.87). Tivantinib significantly improved OS in patients with
high levels of MET expression. Tivantinib was shown to increase the risk of
anemia and neutropenia. Interpretation: Tivantinib was better in prolonging PFS
(not OS) in patients with solid tumors. High MET expression cancers may benefit
from tivantinib. Tivantinib appeared to be well-tolerated by patients.
PMID- 29348895
TI - Upregulated SOX9 expression indicates worse prognosis in solid tumors: a
systematic review and meta-analysis.
AB - It was recently reported that increased SOX9 expression drives tumor growth and
promotes cancer invasion during human tumorigenicity and metastasis. However, the
prognostic value of SOX9 for the survival of patients with solid tumors remains
controversial. The present meta-analysis was thus performed to highlight the link
between dysregulated SOX9 expression and prognosis in cancer patients. A
systematic literature search was conducted using the electronic databases PubMed,
Web of Science and Embase to identify eligible studies. A random-effects meta
analytical model was employed to correlate SOX9 expression with overall survival
(OS), disease-free survival (DFS) and clinicopathological features. In total, 17
studies with 3307 patients were eligible for the final analysis. Combined hazard
ratios (HRs) and 95% confidence intervals (CIs) suggested that high SOX9
expression has an unfavourable impact on OS (HR = 1.66, 95% CI 1.36-2.02, P <
0.001) and DFS (HR = 3.54, 95% CI 2.29-5.47, P = 0.008) in multivariate analysis.
Additionally, the pooled odds ratios (ORs) indicated that SOX9 over-expression is
associated with large tumor size, lymph node metastasis, distant metastasis and a
higher clinical stage. Overall, these results indicated that SOX9 over-expression
in patients with solid tumors might be related to poor prognosis and could serve
as a potential predictive marker of poor clinicopathological prognosis factor.
PMID- 29348896
TI - Prognostic value of long non-coding RNA PVT1 as a novel biomarker in various
cancers: a meta-analysis.
AB - Background: Plasmacytoma variant translocation 1 (PVT1) has recently been
reported to be aberrantly expressed and serves as a prognostic biomarker in many
types of cancers. However, its prognostic significance remains controversial.
Here, we conducted a meta-analysis to investigate the prognostic value of PVT1
expression in cancers. Results: A total of 2109 patients from 20 studies were
included. The results showed that elevated PVT1 expression predicted a poor
outcome for overall survival (OS) in nine types of cancers (HR = 1.40, 95% CI:
1.21-1.59). Subgroup analysis indicated that there was a significant association
between PVT1 overexpression and poor OS of patients with gastric cancer,
gynecology cancer and lung cancer. Furthermore, we also found a negative
significant relationship between PVT1 expression and disease-free survival (HR =
1.83, 95% CI: 1.39-2.27), progression-free survival (HR = 1.63, 95% CI: 1.34
1.93) and recurrence-free survival (HR = 1.74, 95% CI: 1.01-2.47). In addition,
the level of PVT1 expression was positively related to tumor size, TNM stage,
lymph node metastasis and distant metastases. Materials and Methods: A systematic
search was performed through the PubMed, EMBASE, Web of Science, Ovid and
Cochrane library databases for eligible studies on prognostic value of PVT1 in
cancers from inception up to June, 2017. The pooled hazard ratios (HRs) or odds
ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the
association between PVT1 expression and clinical outcomes. Conclusions: PVT1
expression positively related to tumor size, TNM stages, lymph node metastasis
and distant metastases, and served as a prognostic biomarker in different types
of cancers.
PMID- 29348897
TI - Interferon-alpha adjuvant therapy decreases the recurrence of early clear cell
renal cell carcinoma and improves the prognosis of Chinese patients.
AB - The survival time of patients with early clear cell renal cell carcinoma (ccRCC)
is fairly long, but 20% to 30% of patients with localized tumors experience
relapse, and the effect of IFN-alpha on survival has not been well studied in
patients with early ccRCC. In this study, 208 patients with early ccRCC were
treated with surgery, and 54 of the patients received IFN-alpha as adjuvant
therapy. The remaining 115 patients were treated with surgery but not with IFN
alpha therapy. The primary endpoint was the recurrence rate, 20.37% (11/54) and
33.04% (38/115) in the IFN-alpha and surgery-only group, respectively. The
secondary endpoint was progression-free survival (PFS), which was 123.70 (95% CI:
107.18-140.22) months for the IFN-alpha group, and 95.80 (95% CI: 82.18-109.42)
months for the non-IFN-alpha group; this difference was significant (P < 0.05).
The main side effects were pyrexia (61.11%), muscle pain (24.07%), malaise
(9.26%), anorexia (5.56%), hepatic dysfunction (3.70%) and renal dysfunction
(1.85%). Moreover, a multivariate regression identified older age, higher BMI
index and smoking as significant and independent predictors of decreased PFS (P <
0.05). Overall, IFN-alpha therapy significantly improved PFS in Chinese patients
with early ccRCC and was an independent prognostic factor (P < 0.05). In
conclusion, our study showed that adjuvant IFN-alpha therapy decreased the
recurrence rate and prolonged PFS in patients with ccRCC. Thus, this treatment
may help clinicians to select a better treatment modality and better predict
survival in these patients.
PMID- 29348898
TI - Avoiding thermal injury during near-infrared photoimmunotherapy (NIR-PIT): the
importance of NIR light power density.
AB - Near-infrared photoimmunotherapy (NIR-PIT) is a newly-established cancer
treatment which employs the combination of an antibody-photoabsorber conjugate
(APC) and NIR light. When NIR light is absorbed by APC-bound tissues, a certain
amount of heat is generated locally. For the most part this results in a
subclinical rise in skin temperature, however, excessive light exposure may cause
non-specific thermal damage. In this study, we investigated the potential for
thermal damage caused by NIR-PIT by measuring surface temperature. Two sources of
light, laser and light emitting diode (LED), were compared in a mouse tumor
model. First, we found that the skin was heated rapidly by NIR light regardless
of whether laser or LED light sources were used. Air cooling at the surface
reduced the rise in temperature. There were no associations between the rise of
skin temperature and tumor volume of the treated tumor, or APC concentration.
Second, we investigated the extent of thermal damage to the skin at various light
doses. We detected burn injuries 1 day after NIR-PIT, when the NIR light was at a
power density higher than 600 mW/cm2. Successful treatments at lower power
density could be achieved if the total light energy absorbed by the tumor was the
same, i.e. by extending the duration of light exposure. In conclusion, this study
demonstrates that thermal injury after NIR-PIT can be avoided by either employing
a cooling system or by lowering the power density of the light source and
prolonging the exposure time such that the total energy is constant. Thus,
thermal damage is preventable side effect of NIR-PIT.
PMID- 29348899
TI - Curative versus palliative treatments for colorectal cancer with peritoneal
carcinomatosis: a systematic review and meta-analysis.
AB - The objective of this study was to provide an up-to-date summary of the current
evidence that may be useful for updating guidelines. We comprehensively searched
the published literatures and conferences for studies that compared curative with
palliative treatments in colorectal cancer patients with peritoneal metastasis.
The primary outcomes considered in this study were three- and five-year overall
survival rates. We pooled data across studies and estimated summary effect sizes.
Overall, patients who received curative treatments had improved three-year
survival (hazard ratio (HR), 2.19 [95% CI, 1.83 to 2.62]) and five-year survival
(HR, 2.22 [95% CI, 1.83 to 2.69]) compared with those who received palliative
treatments. Patients who received curative treatments had an increased risk of
treatment-related morbidity (odds ratio (OR), 2.90 [95% CI, 2.02 to 4.17]), but
there was no significant difference in treatment-related mortality between
patients who received curative treatments and those who received palliative
treatments (OR, 1.46 [CI, 0.62 to 3.47]). Curative treatments improved overall
survival in colorectal cancer patients with peritoneal metastasis and did not
increase the risk of treatment-related mortality. Curative treatments were
associated with a higher risk of treatment-related morbidity. These data
highlight the importance for further investigation aimed at prevention of
treatment-associated morbidity.
PMID- 29348900
TI - Validation of risk prediction models for the development of HBV-related HCC: a
retrospective multi-center 10-year follow-up cohort study.
AB - Recently, modified REACH-B (mREACH-B) risk prediction model for hepatocellular
carcinoma (HCC) development was proposed. We validated the accuracy of the mREACH
B model and compared its accuracy with those of other prediction models. Between
2006 and 2012, 1,241 patients with chronic hepatitis B (CHB) were recruited. All
patients underwent transient elastography at enrollment. The median age of the
study population (840 males, 401 females) was 49 years. The median PAGE-B, LSM
HCC, and mREACH-B values were 10, 10, and 8, respectively. Among patients without
cirrhosis (n = 940, 75.7%), the median REACH-B value was 9. During the follow-up
period (median 77.4 months), 66 (5.3%) and 83 (6.7%) patients developed HCC and
liver-related events (LRE), respectively. Higher liver stiffness (LS)
independently predicted HCC (hazard ratio [HR] = 1.047) and LRE development (HR =
1.047) (all P < 0.05). The mREACH-B significantly predicted HCC (AUC = 0.824 at 3
year and 0.750 at 5-year) and LRE development (AUC = 0.782 at 3-year and 0.739 at
5-year) (all P < 0.001) and it performed similarly or significantly better than
the PAGE-B and LSM-HCC (AUC = 0.715-0.809 at 3-year and 0.719-0.742 at 5-year for
HCC; AUC = 0.704-0.777 at 3-year and 0.721-0.735 at 5-year for LRE). Among
patients without cirrhosis, mREACH-B predicted HCC (AUC = 0.803 vs. 0.654-0.816
at 3-year and 0.684 vs. 0.639-0.738 at 5-year) and LRE development (AUC = 0.734
vs. 0.619-0.789 at 3-year and 0.674 vs. 0.626-0.729 at 5-year) similarly to PAGE
B, REACH-B, and LSM-HCC. mREACH-B appropriately predicted HCC and LRE development
in patients with CHB and showed similar or superior accuracy to those of PAGE-B,
REACH-B, and LSM-HCC.
PMID- 29348901
TI - Prevalence and risk factors of lower urinary tract symptoms in Chinese adult men:
a multicentre cross-sectional study.
AB - There has been no previous population-based study reporting the prevalence and
risk factors of male lower urinary tract symptoms (LUTS) among men in mainland
China. This cross-sectional study was conducted from 2013 to 2014 in three
representative provinces of China: Guangdong, Hubei and Jiangsu. 3250 individuals
participated in the interviews, which involved a questionnaire covering
sociodemographic characteristics, lifestyle, dietary patterns and the
International Prostate Symptom Score (IPSS). Blood was collected for lipids,
glucose, insulin and reproductive hormone tests. The incidences of LUTS and its
obstructive and irritative symptoms were calculated. Risk factors for LUTS were
identified using multivariable logistic regression analysis. The prevalence of
moderate to severe LUTS and its obstructive and irritative symptoms was 14.3%,
13.1% and 16.1%, respectively, and increased with age. The prevalence in
Guangdong was much lower than that in Hubei and Jiangsu in different ages.
Increased fasting plasma glucose and decreased HDL-C levels were associated with
an increased risk of moderate to severe LUTS (OR = 1.30, 95% CI: 1.02-1.65 and OR
= 2.06, 95% CI: 1.08-3.94, respectively). Free testosterone < 0.22 ng/ml
decreased the risk of moderate to severe LUTS and obstructive and irritative
symptoms by about 20-30%. An inadequate daily intake of vegetables, fruit and
water significantly increased the risk of LUTS by 1.3-to 2.0 times. In
conclusion, the prevalence of LUTS in Chinese men is high and increases with age.
Dietary patterns may be critical for the development of LUTS. Thus, dietary
modifications could be a useful strategy for preventing the development of LUTS.
PMID- 29348902
TI - Feasibility and outcome of primary laparoscopic cytoreductive surgery for
advanced epithelial ovarian cancer: a comparison to laparotomic surgery in
retrospective cohorts.
AB - Objectives: To assess the feasibility and outcome of primary laparoscopic
cytoreductive surgery on advanced epithelial ovarian cancer in comparison with
conventional open surgery. Materials and Methods: Patients undergoing primary
laparoscopic cytoreductive surgery (LCS) from March 2007 to December 2016 were
matched to controls treated with laparotomic cytoreduction during the same
period. Procedural data and outcomes were analyzed. Results: The LCS group (n =
64) and laparotomic group (n = 68) had similar age, BMI, stages, histologic type
and grading. The LCS group exhibited significantly less operating time (P <
0.001), less intraoperative blood loss (P < 0.001), and shorter time to recover
postoperatively (P = 0.002). No statistical difference was observed for the
number of pelvic and para-aortic lymph nodes dissected (P = 0.326 and P = 0.151).
Significant difference was observed in satisfaction of the cytoreduction (95.3%
vs. 76.5%, P = 0.008). No significant difference were observed either in intra
operative or in post-operative complications between the two groups (P = 0.250).
Three patients in the LCS group experienced intra-operative complications (4.7%)
and were all treated laparoscopically. The conversion rate was 3.1%. No
significant differences were observed in the progression-free survival and
overall survival between the two groups during the medium follow-up of 18 months
(P = 0.236 and P = 0.216). The 2-year and 3-year progression-free survival was
67.9%, 55.5% in LCS group and 53.8%, 33.3% respectively in the control group. The
2-year and 3-year overall survival was 95.8%, 88.7% respectively in the LCS group
and 89.0%, 83.7% in the control group. Conclusions: Primary laparoscopic
cytoreductive surgery in some strictly selected advanced stages of EOC patients
was feasible and safe, resulting in oncologic outcomes not inferior to those in
open surgery.
PMID- 29348903
TI - The systemic inflammation-based Glasgow Prognostic Score as a powerful prognostic
factor in patients with upper tract urothelial carcinoma.
AB - Introduction and Objective: The combination of C-reactive protein and albumin,
the Glasgow Prognostic Score (GPS), had independent prognostic value in patients
with varying cancers, except for upper tract urothelial carcinoma (UTUC). The aim
of this study was to describe the relationship between GPS and survival in
patients with UTUC after adjustment for other prognostic factors. Materials and
Methods: We queried 2 UTUC databases. Retrospective clinical series on patients
with localized UTUC managed by nephroureterectomy with bladder cuff, for whom
data from the Yamaguchi Uro-Oncology Group and Osaka Medical College registry,
including age, presence of bladder cancer, pT stage, lymphovascular invasion, C
reactive protein (CRP) and albumin, were analyzed. The GPS was constructed by
combining CRP and albumin. Cancer specific survival (CSS) and overall survival
(OS) and relative excess risk of death were estimated by GPS categories after
adjusting for gender, age, ECOG performance status (PS), grade, and
lymphovascular invasion (LVI). Results: Seven hundred and twenty four UTUC
patients were identified. Our final cohort included 574 patients; of these, 29.2%
died during a maximum follow up of 16.7 years. The estimated mean 10-year CSS of
patients with GPS of scre-0, -1, and -2 was 99.5, 95.1, and 75.9 months,
respectively. Patients with GPS of score-2 had poorest 10-year estimated mean OS
of 67.6 months (57.2-77.9). Raised GPS also had a significant association with
excess risk of cancer death at 10 years (GPS 2: Relative Excess Risk = 1.74, 95%
CI 1.20-2.54) after adjusting for gender, patients' age, ECOG PS, and tumor
focality. C-index of GPS both for CSS and OS were superior to patients' age and
tumor focality, and comparable to grade. Conclusions: The GPS is an independent
prognostic factor for CSS and OS after surgery with curative intent for localized
UTUC. It significantly increases the accuracy of established prognostic factors.
The GPS may provide a meaningful adjunct for patient counseling and clinical
trial design.
PMID- 29348904
TI - Role of tissue-type plasminogen activator and plasminogen activator inhibitor-1
in psychological stress and depression.
AB - Major depressive disorder is a common illness worldwide, but the pathogenesis of
the disorder remains incompletely understood. The tissue-type plasminogen
activator-plasminogen proteolytic cascade is highly expressed in the brain
regions involved in mood regulation and neuroplasticity. Accumulating evidence
from animal and human studies suggests that tissue-type plasminogen activator and
its chief inhibitor, plasminogen activator inhibitor-1, are related to stress
reaction and depression. Furthermore, the neurotrophic hypothesis of depression
postulates that compromised neurotrophin brain-derived neurotrophic factor (BDNF)
function is directly involved in the pathophysiology of depression. In the brain,
the proteolytic cleavage of proBDNF, a BDNF precursor, to mature BDNF through
plasmin represents one mechanism that can change the direction of BDNF action. We
also discuss the implications of tissue-type plasminogen activator and
plasminogen activator inhibitor-1 alterations as biomarkers for major depressive
disorder. Using drugs that increase tissue-type plasminogen activator or decrease
plasminogen activator inhibitor-1 levels may open new avenues to develop
conceptually novel therapeutic strategies for depression treatment.
PMID- 29348906
TI - An ANK1 IVS3-2A>C mutation causes exon 4 skipping in two patients from a Chinese
family with hereditary spherocytosis.
AB - Hereditary spherocytosis (HS) is a congenital hemolytic anemia that affects the
cell membrane of red blood cells and is characterized by the presence of
spherical-shaped erythrocytes in the peripheral blood film. The clinical
manifestation of HS ranges from asymptomatic to severe cases that require
transfusion during early childhood. HS is caused by mutations in red blood cell
membrane protein encoding genes, including ANK1, EPB42, SLC4A1, SPTA1, and SPTB.
Mutations of the ANK1 gene account for 75% of all HS cases, and these particular
mutations are typically inherited in an autosomal dominant manner. In this study,
heterozygous an ANK1 IVS3-2A>C mutation was identified in a 7-year-old girl with
Coombs-negative and severe hemolytic jaundice using targeted next-generation
sequencing (NGS) and Sanger sequencing. Spherocytes were observed in a peripheral
smear. Osmotic fragility was increased, and glucose-6-phosphate dehydrogenase
(G6PD) activity was normal. A genetic mutation screen for alpha- and beta
thalassemia was negative. Autoimmune antibody tests were negative. Both the girl
and her affected father received a splenectomy. Patient-derived peripheral blood
mononuclear cells showed skipping of exon 4 in the mRNA, which confirmed the
splicing mutation effect of the ANK1 IVS3-2A>C mutation. Moreover, the anemia was
ameliorated after splenectomy. Our results demonstrate that the ANK1 IVS3-2A>C
mutation may lead to exon 4 skipping of the ANK1 gene and cause HS.
PMID- 29348905
TI - Bridging the divide: preclinical research discrepancies between triple-negative
breast cancer cell lines and patient tumors.
AB - Triple-negative breast cancer (TNBC) is the most refractory subtype of breast
cancer and disproportionately accounts for the majority of breast cancer related
deaths. Effective treatment of this disease remains an unmet medical need. Over
the past several decades, TNBC cell lines have been used as the foundation for
drug development and disease modeling. However, ever-mounting research
demonstrates striking differences between cell lines and clinical TNBC tumors,
disconnecting bench research and actual clinical responses. In this review, we
discuss the limitations of cell lines and the importance of using patients'
tumors for translational research, and highlight the usage of patient-derived
xenograft (PDXs) models that have emerged as a clinically relevant platform for
preclinical studies. PDX tumors possess tumor heterogeneity with similar
cellular, molecular, genetic and epigenetic properties akin to those found within
patients' tumors. Moreover, PDX and clinical tumors possess abnormal vasculature
with higher blood vessel permeability, a feature that is not always demonstrated
in in vivo cell line xenografts. Development of clinically relevant, novel drug
nanoparticles capable of accumulating in PDX tumors through the enhanced
permeability and retention effect in tumor vasculature may lead to new and
effective TNBC treatments.
PMID- 29348907
TI - Microsatellite stability and mismatch repair proficiency in nasopharyngeal
carcinoma may not predict programmed death-1 blockade resistance.
AB - The US FDA granted accelerated approval to pembrolizumab for microsatellite
instability-high and mismatch repair deficient cancers. The response of
programmed death-1 blockade in mismatch repair proficiency (pMMR) colorectal
cancer is very poor, however, whether such treatment is effective in pMMR
nasopharyngeal carcinoma (NPC) remains unknown. We report a case of a 51-year-old
man with NPC. PET-CT scan revealed a space-occupying lesion in the left lung, and
the pathologic result confirmed the occupying lesion originated from NPC.
Meanwhile, both immunohistochemistry and PCR revealed that the occupying lesion
belonged to pMMR NPC. The lung lesions largely shrunk after chemoradiotherapy.
One year later, MRI showed brain occupancy, and brain lesion resection surgery
was performed subsequently. The resected tissue was also validated to be the
metastatic lesion from NPC. After one month, the patient was examined again by
PET-CT, which showed multiple metastases in the liver, pelvis and adrenal gland.
Since January 2017, the patient has been treated with pembrolizumab therapy.
After five courses of treatment, both PET-CT and blood testing were repeated and
demonstrated that metastases and serum Epstein-Barr virus DNA almost completely
disappeared. We provide the first report that pembrolizumab has a confirmed
objective response to microsatellite stability and pMMR NPC, and two biomarkers
may not be sufficient to identify patients who might be resistant to such
treatment in NPC.
PMID- 29348908
TI - Correlation Clustering of Stable Angina Clinical Care Patterns for 506 Thousand
Patients.
AB - Objectives: Our goal was to apply statistical and network science techniques to
depict how the clinical pathways of patients can be used to characterize the
practices of care providers. Methods: We included the data of 506,087 patients
who underwent procedures related to ischemic heart disease. Patients were
assigned to one of the 136 primary health-care centers using a voting scheme
based on their residence. The clinical pathways were classified, and the spectrum
of the pathway types was computed for each center, then a network was built with
the centers as nodes and spectrum correlations as edge weights. Then Louvain
clustering was used to group centers with similar pathway spectra. Results: We
identified 3 clusters with rather distinct characteristics that occupy quite
compact spatial areas, though no geographical information was used in clustering.
Network analysis and hierarchical clustering show the dominance of medical
university clinics in each cluster. Conclusion: Though clinical guidelines
provide a uniform regulation for medical decisions, doctors have great freedom in
daily clinical practice. This freedom leads to regional preferences of certain
clinical pathways, the intercenter professional links, and geographical locality
and coupled with quantifiable consequences in terms of care costs and
periprocedural risk of patients.
PMID- 29348909
TI - Functionalized cationic [4]helicenes with unique tuning of absorption,
fluorescence and chiroptical properties up to the far-red range.
AB - Unprecedented regioselective post-functionalization of racemic and enantiopure
cationic diaza [4]helicenes is afforded. The peripheral auxochrome substituents
allow a general tuning of the electrochemical, photophysical and chiroptical
properties of the helical dyes (26 examples). For instance, electronic absorption
and circular dichroism are modulated from the orange to near-infrared spectral
range (575-750 nm), fluorescence quantum efficiency is enhanced up to 0.55 (631
nm) and circularly polarized luminescence is recorded in the red (|glum| ~ 10-3).
PMID- 29348910
TI - Determinants of Colour Constancy and the Blue Bias.
AB - We investigated several sensory and cognitive determinants of colour constancy
across 40 illumination hues. In the first experiment, we measured colour naming
for the illumination and for the colour induced by the illumination on the
colorimetric grey. Results confirmed that the induced colours are approximately
complementary to the colour of the illumination. In the second experiment, we
measured colour constancy using achromatic adjustments. Average colour constancy
was perfect under the blue daylight illumination and decreased in colour
directions away from the blue daylight illumination due to undershooting and a
strong blue bias. Apart from this blue bias, colour constancy was not related to
illumination discrimination and to chromatic detection measured previously with
the same setup and stimuli. We also observed a strong negative relationship
between the degree of colour constancy and the consensus of naming the
illumination colour. Constancy coincided with a low naming consensus, in
particular because bluish illumination colours were sometimes seen as achromatic.
Blue bias and category consensus alone explained >68%, and all determinants
together explained >94% of the variance of achromatic adjustments. These findings
suggest that colour constancy is optimised for blue daylight.
PMID- 29348911
TI - Reduction of Flicker in Four-Stroke Motion of Color Images.
AB - When two sequential video frames extracted from a single video clip are followed
by the negative of the two frames, a viewer often experiences a visual illusion
whereby a scene in the frames continuously moves in a single direction (four
stroke apparent motion). To create a four-stroke apparent motion display, the
image intensities of the whole of the second pair of images are reversed.
However, this intensity reversal creates a strong impression of flicker that can
be undesirable for comfortable viewing. This study reports that four-stroke
apparent motion can be induced by only reversing the luminance intensities in
those spatial areas which contain motion signals in high-pass filtered images.
This use of only a partial reversal of image intensities greatly reduces the
apparent flicker in the display while retaining motion perception.
PMID- 29348913
TI - Complications during removal of stainless steel versus titanium nails used for
intramedullary nailing of diaphyseal fractures of the tibia.
AB - Objectives: Intramedullary nailing is the treatment of choice for fractures of
the tibial shaft, which might necessitate the nail removal due to complications
in the long-term. Although considered as a low-risk procedure, intramedullary
nail removal is also associated with certain complications. Here, we compared the
most commonly used stainless steel and titanium nails with respect to the
complications during removal and clinical outcome for intramedullary nailing of
diaphyseal fractures of the tibia. Patients and methods: Sixty-two patients (26
females, 36 males) were included in this retrospective study. Of the removed
nails, 24 were of stainless steel and 38 of titanium. Preoperative and
intraoperative parameters, such as implant discomfort, anterior knee pain,
operating time and amount of bleeding, and postoperative outcomes were evaluated
for each patient. Results: Titanium nail group had more, but not statistically
significant, intraoperative complications than stainless steel group during the
removal of nails (p = .4498). Operating time and amount of intraoperative
bleeding were significantly higher in titanium group than stainless steel group
(p = .0306 and p < .001, respectively). Preoperative SF-36 physical component and
KSS scores were significantly lower in patients who had removal of titanium nails
than those of stainless steel nails, whereas there was no difference in terms of
postoperative SF-36 and KSS scores. Conclusion: In conclusion, although greater
bone contact with titanium increases implant stability, nail removal is more
difficult, resulting in more longer surgical operation and more intraoperative
bleeding. Therefore, we do not recommend titanium nail removal in asymptomatic
patients.
PMID- 29348912
TI - Genomic and molecular control of cell type and cell type conversions.
AB - Organisms are made of a limited number of cell types that combine to form higher
order tissues and organs. Cell types have traditionally been defined by their
morphologies or biological activity, yet the underlying molecular controls of
cell type remain unclear. The onset of single cell technologies, and more
recently genomics (particularly single cell genomics), has substantially
increased the understanding of the concept of cell type, but has also increased
the complexity of this understanding. These new technologies have added a new
genome wide molecular dimension to the description of cell type, with genome-wide
expression and epigenetic data acting as a cell type 'fingerprint' to describe
the cell state. Using these genomic fingerprints cell types are being
increasingly defined based on specific genomic and molecular criteria, without
necessarily a distinct biological function. In this review, we will discuss the
molecular definitions of cell types and cell type control, and particularly how
endogenous and exogenous transcription factors can control cell types and cell
type conversions.
PMID- 29348914
TI - Exploring health insurance services in Sudan from the perspectives of insurers.
AB - Background: It has been 20 years since the introduction of health insurance in
Sudan. This study was the first one that explored health insurance services in
Sudan from the perspectives of the insurers. Methods: This was a qualitative,
exploratory, interview study. The sampling frame was the list of Social Health
Insurance and Private Health Insurance institutions in Sudan. Participants were
selected from the four Social Health Insurance institutions and from five Private
Health Insurance companies. The study was conducted in January and February 2017.
In-depth individual interviews were conducted with a convenient sample of key
executives from the different health insurers. Ideas and themes were identified
and analysed using thematic analysis. Results: The result showed that universal
coverage was not achieved despite long time presence of Social Health Insurance
and Private Health Insurance in Sudan. All participants described their services
as comprehensive. All participants have good perception of the quality of the
services they provide, although none of them investigated customer satisfaction.
The main challenges facing Social Health Insurance are achieving universal
coverage, ensuring sustainability and recruitment of the informal sector and self
employed population. Consumers' affordability of the premiums is the main
obstacle for Private Health Insurance, while rising healthcare cost due to
economic inflation is a challenge facing both Social Health Insurance and Private
Health Insurance. Conclusion: In spite of the presence of Social Health Insurance
and Private Health Insurance in Sudan, the country is still far from achieving
universal coverage. Moreover, the sustainability of health insurance is
questionable. The main reasons include low governmental financial resources and
lack of affordability by beneficiaries especially for Private Health Insurance.
This necessitates finding solutions to improve them or trying other types of
health insurance. The quality of services provided by Social Health Insurance and
Private Health Insurance was described as good, but no insurance in Sudan
measured customer satisfaction as yet.
PMID- 29348915
TI - Extended posterior approach for huge popliteal aneurysm extended to superficial
femoral artery.
AB - Objectives: Generally, popliteal artery aneurysms have been addressed surgically
by a medial, posterior, or lateral approach. We have designed a new posterior
approach that exposes the superficial femoral artery and entire popliteal artery
without dividing any muscles in a just prone position. Methods and results: A 72
year old man with huge popliteal aneurysm extended to superficial femoral artery
was admitted to our hospital. Surgery was performed due to a high risk of
rupture. An S-shaped skin incision was made in the popliteal fossa. We could not
expose the proximal side of the giant aneurysm proximal to the foramen of the
adductor magnus. We extended the skin incision to the proximal and exfoliated the
medial side of semitendinosus muscle. We could expose the superficial femoral
artery in this approach like in a medial approach. We could perform the
interposition of great saphenous vein. Conclusion: The advantages of this
approach allowed for entire exposure of the popliteal aneurysm in the same
patient's position when we perform aneurysmectomy and bypass. It is possible for
this approach to provide easy access to the superficial femoral artery proximal
to the adductor hiatus and distal below-knee popliteal artery including the
tibioperoneal trunk.
PMID- 29348916
TI - An intravascular papillary endothelial hyperplasia of the hand radiologically
mimicking a hemangiopericytoma: A case report and literature review.
AB - Intravascular papillary endothelial hyperplasia is a rare benign vascular lesion
of the skin and subcutaneous tissues, characterized by a reactive proliferation
of endothelial cells that can present de novo in normal blood vessels (primary
intravascular papillary endothelial hyperplasia), but it can also develop from a
pre-existing vascular process (type II intravascular papillary endothelial
hyperplasia), or it can arise in an extravascular location from a post-traumatic
haematoma. The differential diagnosis between intravascular papillary endothelial
hyperplasia and malignant vascular tumours can be challenging, due to the lacking
of a specific radiologic description. We present a case of intravascular
papillary endothelial hyperplasia of the hand radiologically mimicking a
hemangiopericytoma.
PMID- 29348917
TI - Refractory actinomycosis of the humerus.
AB - Actinomycosis is a chronic, opportunistic infection caused by Actinomyces
species, such as Actinomyces bacillus. Actinomycosis in long bones is very rare.
To the best of our knowledge, isolated primary actinomycosis of the humerus is
rarely reported in literature. We present a rare case of a refractory primary
actinomycosis of the humerus. A 66-year-old man with no history of concomitant
conditions was admitted to our hospital with a history of a tumour on the distal
third of the left arm as a result of a closed trauma without fracture 20 years
before. Pathological anatomy samples showed the presence of Actinomyces. Cultures
were subjected to a prolonged incubation of 21 days under aerobic and anaerobic
conditions and were always negative. He underwent several surgical procedures and
received long-term antibiotic therapy with poor outcome. Primary actinomycosis in
long bones is uncommon. Diagnosis may be challenging: considering the small
number of case studies reported in the literature, symptoms are not specific, and
the organism is difficult to isolate. Antibiotic treatment may not be sufficient
to improve the clinical condition, and surgical alternatives should be
considered.
PMID- 29348918
TI - Safety and timing of resuming dabigatran after major gastrointestinal bleeding
reversed by idarucizumab.
AB - The recent introduction of direct oral anticoagulants, including rivaroxaban,
dabigatran, apixaban, and edoxaban, for the acute treatment and secondary
prevention of venous thromboembolism and in atrial fibrillation has been shown to
provide greater clinical benefit than oral vitamin K antagonists. However, direct
oral anticoagulants are associated with adverse events, the most common being
major bleeding; such events require the reversal of the anticoagulant effects by
specific agents. In this case report, we describe an 87-year-old female with
atrial fibrillation treated with dabigatran who had massive rectal bleeding.
Idarucizumab 5 g (2 * 2.5 g/50 mL) was successfully used to reverse dabigatran
effect; subsequent to this, treatment with dabigatran was resumed, and there were
no further bleeding events. This suggests that dabigatran can be safely restarted
after major bleeding, but this outcome needs to be confirmed in studies involving
larger groups of patients.
PMID- 29348919
TI - Thoracic stent graft placement for repair of iatrogenic aortic injury secondary
to sheath placement during pacemaker insertion.
AB - We describe the inadvertent cannulation of the proximal descending thoracic
aortic stent with a five French sheath during attempted pacemaker placement in an
88- year-old male. The injury was managed successfully by the percutaneous
placement of a thoracic aortic stent graft with good outcome. Our case highlights
the feasibility of managing this uncommon injury with this technique.
PMID- 29348920
TI - Wiskott-Aldrich syndrome that was initially diagnosed as immune thrombocytopenic
purpura secondary to a cytomegalovirus infection.
AB - Wiskott-Aldrich syndrome is a rare X-linked recessive disease resulting from
variations in the WAS gene. Wiskott-Aldrich syndrome is sometimes difficult to
differentiate from immune thrombocytopenic purpura. A 2-month-old boy was
admitted to our hospital for purpura and thrombocytopenia. His mean platelet
volume was reported to be normal. Treatment with intravenous immunoglobulins
failed to improve the patient's platelet count. Subsequently, an acute
cytomegalovirus infection was confirmed by serological testing and antigenemia.
The patient was diagnosed with immune thrombocytopenic purpura secondary to a
cytomegalovirus infection. However, based on the patient's clinical course and
the refractoriness of his condition, Wiskott-Aldrich syndrome was strongly
suspected. Through direct sequencing of the genomic DNA of the Wiskott-Aldrich
syndrome protein (WASP) gene, we identified a novel missense mutation in exon 3
of the patient's WASP gene (c. 343 C>T, p. H115T), and the patient was diagnosed
with Wiskott-Aldrich syndrome at 3 months after onset. Children with Wiskott
Aldrich syndrome are often initially diagnosed with immune thrombocytopenic
purpura, which can lead to inappropriate treatment and delays to life-saving
definitive therapy. Our findings imply that Wiskott-Aldrich syndrome should be
considered as a differential diagnosis in cases of refractory immune
thrombocytopenic purpura combined with a cytomegalovirus infection.
PMID- 29348921
TI - Genetic characteristics of VanA-type vancomycin-resistant Enterococcus faecalis
and Enterococcus faecium in Cuba.
AB - VanA-type vancomycin-resistant enterococci isolates from bloodstream infections
in Cuba were genetically characterized. Enterococcus faecalis isolates were
assigned to sequence type (ST) 28, closely related to Eastern Europe, while
Enterococcus faecium belonged to ST262, ST656 and ST1349, and showed different
genetic profiles.
PMID- 29348922
TI - Taxonogenomic description of four new Clostridium species isolated from human
gut: 'Clostridium amazonitimonense', 'Clostridium merdae', 'Clostridium
massilidielmoense' and 'Clostridium nigeriense'.
AB - Culturomics investigates microbial diversity of the human microbiome by combining
diversified culture conditions, matrix-assisted laser desorption/ionization time
of-flight mass spectrometry and 16S rRNA gene identification. The present study
allowed identification of four putative new Clostridium sensu stricto species:
'Clostridium amazonitimonense' strain LF2T, 'Clostridium massilidielmoense'
strain MT26T, 'Clostridium nigeriense' strain Marseille-P2414T and 'Clostridium
merdae' strain Marseille-P2953T, which we describe using the concept of
taxonogenomics. We describe the main characteristics of each bacterium and
present their complete genome sequence and annotation.
PMID- 29348923
TI - Cervicofacial lymphadenitis due to Mycobacterium mantenii: rapid and reliable
identification by MALDI-TOF MS.
PMID- 29348924
TI - Mortality and Hospitalizations in Intensive Dialysis: A Systematic Review and
Meta-Analysis.
AB - Background: Survival and hospitalization are critically important outcomes
considered when choosing between intensive hemodialysis (HD), conventional HD,
and peritoneal dialysis (PD). However, the comparative effectiveness of these
modalities is unclear. Objective: We had the following aims: (1) to compare the
association of mortality and hospitalization in patients undergoing intensive HD,
compared with conventional HD or PD and (2) to appraise the methodological
quality of the supporting evidence. Data Sources: MEDLINE, Embase, ISI Web of
Science, CENTRAL, and nephrology conference abstracts. Study Eligibility
Participants and Interventions: We included cohort studies with comparator arm,
and randomized controlled trials (RCTs) with >50% of adult patients (>=18 years)
comparing any form of intensive HD (>4 sessions/wk or >5.5 h/session) with any
form of chronic dialysis (PD, HD <=4 sessions/wk or <=5.5 h/session), that
reported at least 1 predefined outcome (mortality or hospitalization). Methods:
We used the GRADE approach to systematic reviews and quality appraisal. Two
reviewers screened citations and full-text articles, and extracted study-level
data independently, with discrepancies resolved by consensus. We pooled effect
estimates of randomized and observational studies separately using generic
inverse variance with random effects models, and used fixed-effects models when
only 2 studies were available for pooling. Predefined subgroups for the intensive
HD cohorts were classified by nocturnal versus short daily HD and home versus in
center HD. Results: Twenty-three studies with a total of 70 506 patients were
included. Of the observational studies, compared with PD, intensive HD had a
significantly lower mortality risk (hazard ratio [HR]: 0.67; 95% confidence
interval [CI]: 0.53-0.84; I2 = 91%). Compared with conventional HD, home
nocturnal (HR: 0.46; 95% CI: 0.38-0.55; I2 = 0%), in-center nocturnal (HR: 0.73;
95% CI: 0.60-0.90; I2 = 57%) and home short daily (HR: 0.54; 95% CI: 0.31-0.95;
I2 = 82%) intensive regimens had lower mortality. Of the 2 RCTs assessing
mortality, in-center short daily HD had lower mortality (HR: 0.54; 95% CI: 0.31
0.93), while home nocturnal HD had higher mortality (HR: 3.88; 95% CI: 1.27
11.79) in long-term observational follow-up. Hospitalization days per patient
year (mean difference: -1.98; 95% CI: -2.37 to -1.59; I2 = 6%) were lower in
nocturnal compared with conventional HD. Quality of evidence was similarly low or
very low in RCTs (due to imprecision) and observational studies (due to residual
confounding and selection bias). Limitations: The overall quality of evidence was
low or very low for critical outcomes. Outcomes such as quality of life,
transplantation, and vascular access outcomes were not included in our review.
Conclusions: Intensive HD regimens may be associated with reduced mortality and
hospitalization compared with conventional HD or PD. As the quality of supporting
evidence is low, patients who place a high value on survival must be adequately
advised and counseled of risks and benefits when choosing intensive dialysis.
Practice guidelines that promote shared decision-making are likely to be helpful.
PMID- 29348925
TI - Volume Estimates in Chronic Hemodialysis Patients by the Watson Equation and
Bioimpedance Spectroscopy and the Impact on the Kt/Vurea calculation.
AB - Background: Accurate assessment of total body water (TBW) is essential for the
evaluation of dialysis adequacy (Kt/Vurea). The Watson formula, which is
recommended for the calculation of TBW, was derived in healthy volunteers thereby
leading to potentially inaccurate TBW estimates in maintenance hemodialysis
recipients. Bioimpedance spectroscopy (BIS) may be a robust alternative for the
measurement of TBW in hemodialysis recipients. Objectives: The primary objective
of this study was to evaluate the accuracy of Watson formula-derived TBW
estimates as compared with TBW measured with BIS. Second, we aimed to identify
the anthropometric characteristics that are most likely to generate inaccuracy
when using the Watson formula to calculate TBW. Finally, we derived novel
anthropometric equations for the more accurate estimation of TBW. Design and
Setting: This was a cross-sectional study of prevalent in-center HD patients at
St Michael's Hospital. Patients: One hundred eighty-four hemodialysis patients
(109 men and 75 women) were evaluated in this study. Measurements: Anthropometric
measurements including weight, height, waist circumference, midarm circumference,
and 4-site skinfold (biceps, triceps, subscapular, and suprailiac) thickness were
measured; fat mass was measured using the formula by Durnin and Womersley. We
measured TBW by BIS using the Body Composition Monitor (Fresenius Medical Care,
Bad Homburg, Germany). Methods: We used the Bland-Altman method to calculate the
difference between the TBW derived from the Watson method and the BIS. To derive
new equations for TBW estimation, Pearson's correlation coefficients between BIS
TBW (the reference test) and other variables were examined. We used the least
squares regression analysis to develop parsimonious equations to predict TBW.
Results: TBW values based on the Watson method had a high correlation with BIS
TBW (correlation coefficients = 0.87 and P < .001). Despite the high correlation,
the Watson formula overestimated TBW by 5.1 (4.5-5.8) liters and 3.8 (3.0-4.5)
liters, in men and women, respectively. Higher fat mass and waist circumference
(general and abdominal obesity) were correlated with the greater TBW
overestimation by the Watson formula. We created separate equations for men and
women based on weight and waist circumference. Limitations: The main limitation
of our study was the lack of an external validation for our novel estimating
equation. Furthermore, though BIS has been validated against traditional
reference standards, our assumption that it represents the "gold standard" for
body compartment assessment may be flawed. Conclusions: The Watson formula
generally overestimates TBW in chronic dialysis recipients, particularly in
patients with the highest waist circumference. Widespread reliance on the Watson
formula for derivation of TBW may lead to the underestimation of Kt/Vurea..
PMID- 29348926
TI - A double-blind, placebo-controlled, single ascending-dose study of remyelinating
antibody rHIgM22 in people with multiple sclerosis.
AB - Objective: The objective of this paper is to assess, in individuals with
clinically stable multiple sclerosis (MS), the safety, tolerability,
pharmacokinetics (PK) and exploratory pharmacodynamics of the monoclonal
recombinant human antibody IgM22 (rHIgM22). Methods: Seventy-two adults with
stable MS were enrolled in a double-blind, randomized, placebo-controlled, single
ascending-dose, Phase 1 trial examining rHIgM22 from 0.025 to 2.0 mg/kg.
Assessments included MRI, MR spectroscopy, plasma PK, and changes in clinical
status, laboratory values and adverse events for three months. The final cohort
had additional clinical, ophthalmologic, CSF collection and exploratory biomarker
evaluations. Participants were monitored for six months. Results: rHIgM22 was
well tolerated with no clinically significant safety signals. Noncompartmental PK
modeling demonstrated linear dose-proportionality both of Cmax and AUC0-Last. The
steady-state apparent volume of distribution of approximately 58 ml/kg suggested
primarily vascular compartmentalization. CSF:plasma rHIgM22 concentration
increased from 0.003% on Day 2 for both 1.0 and 2.0 mg/kg to 0.056% and 0.586%
for 1.0 and 2.0 mg/kg, respectively, on Day 29. No statistically significant
treatment-related changes were observed in exploratory pharmacodynamic outcome
measures included for the 21 participants of the extension cohort. Conclusions:
Single doses of rHIgM22 were well tolerated and exhibited linear PK, and antibody
was detected in the CSF.
PMID- 29348927
TI - Improved cognitive performance and event-related potential changes following
working memory training in patients with multiple sclerosis.
AB - Background: Few studies of cognitive rehabilitation in multiple sclerosis (MS)
have targeted working memory specifically. Objective: We examined the effects of
n-back working memory training on cognitive performance and brain function in
patients with MS. Methods: Patients with MS (n = 12) and healthy controls (HC; n
= 12) underwent 20 sessions of n-back working memory training. Before and after
training (pre- and posttest) cognitive event-related potential (ERP) measures
were obtained during a 3-back task. In addition, a battery of cognitive tests was
administered. Results: Following n-back training, both MS patients and HCs showed
significant improvement on tests of working memory, processing speed, complex
attention, and reasoning ability. MS and HCs also exhibited an enhancement of N2
ERP component amplitude, and earlier N2 and P3 latencies, following n-back
training. Conclusions: Targeted training of working memory with the n-back task
may improve cognitive function in MS. Enhancement of N2 ERP component amplitude
and shorter N2 and P3 latency following training in patients with MS is
consistent with plasticity of neural processes that are involved in working
memory.
PMID- 29348928
TI - Glaucomatocyclitic Crises May Occur in Patients with Narrow or Closed Angles.
AB - Purpose: To report cases of glaucomatocyclitic crises and discuss the possibility
of occurrence in patients with narrow or closed angles. Background: The
prevalence of angle closure is much higher among Asians than among the Western
population. Currently, there is no evidence for a direct relationship between the
etiology and angle structure. Design: A retrospective and observational case
series. Methods: We retrospectively collected data from nine adult patients
(three males and six females) who were diagnosed with a glaucomatocyclitic crisis
and a shallow anterior chamber over a 21-year period, from 1995 to 2016, at the
Kaohsiung Medical University Hospital. A narrow angle was defined as a grade less
than the Shaffer system grade II. Ophthalmic examinations, including anterior
segment biomicroscopy, direct ophthalmoscopy, intraocular pressure measurements,
anterior chamber reaction, visual field tests, and the grade of the anterior
chamber angle according to the Shaffer system, were reviewed. Results: These
patients experienced at least one typical unilateral ocular hypertensive episode
that fulfilled the criteria of a glaucomatocyclitic crisis without the angle
feature. All patients had gonioscopically narrow or closed angles with or without
peripheral anterior synechiae. Conclusions: The coexistence of narrow or closed
angles and a glaucomatocyclitic crisis is possible, especially in patients of
Asian descent. In patients with shallow anterior chambers, a glaucomatocyclitic
crisis may be a cause of acute glaucoma episodes.
PMID- 29348929
TI - The Influence of Environmental Factors on the Prevalence of Myopia in Poland.
AB - Purpose: In the paper, we describe and discuss the results of epidemiological
studies concerning myopia carried out in Poland. Materials and Methods: Results
from the examination of 5601 Polish school children and students (2688 boys and
2913 girls) aged 6 to 18 years were analyzed. The mean age was 11.9 +/- 3.2
years. Every examined student had undergone the following examinations: distance
visual acuity testing, cover test, anterior segment evaluation, and cycloplegic
retinoscopy after instillation of 1% tropicamide, and a questionnaire was taken.
Results: We have found that (1) intensive near work (writing, reading, and
working on a computer) leads to a higher prevalence of myopia, (2) watching
television does not influence the prevalence of myopia, and (3) being outdoors
decreases the prevalence of myopia. Conclusions: The results of our study point
to insufficiency of accommodation contributing to the pathogenesis of myopia.
PMID- 29348930
TI - Analysis of Genetic Mutations in a Cohort of Hereditary Optic Neuropathy in
Shanghai, China.
AB - Purpose: To evaluate the clinical classification and characteristics of
hereditary optic neuropathy patients in a single center in China. Method:
Retrospective case study. Patients diagnosed with hereditary optic neuropathy
between January 2014 and December 2015 in the neuro-ophthalmology division in
Shanghai Eye and ENT Hospital of Fudan University were recruited. Clinical
features as well as visual field, brain/orbital MRI, and spectrum domain optical
coherence tomography (SD-OCT) were analyzed. Results: Eighty-two patients
diagnosed by gene test were evaluated, including 66 males and 16 females. The
mean age of the patients was 19.4 years (range, 5-46 years). A total of 158 eyes
were analyzed, including 6 unilateral, 61 bilateral, and 15 sequential. The
median duration of the disease was 0.5 year (range, 0.1-20 years). Genetic test
identified 68 patients with Leber hereditary optic neuropathy, 9 with dominant
optic neuropathy, and 2 with a Wolfram gene mutation. There was also one case of
hereditary spastic paraplegia, spinocerebellar ataxia, and polymicrogyria with
optic nerve atrophy, respectively. Conclusion: Leber hereditary optic neuropathy
is the most common detected type of hereditary optic neuropathy in Shanghai,
China. The detection of other autosomal mutations in hereditary optic neuropathy
is limited by the currently available technique.
PMID- 29348931
TI - Detection of Silent Type I Choroidal Neovascular Membrane in Chronic Central
Serous Chorioretinopathy Using En Face Swept-Source Optical Coherence Tomography
Angiography.
AB - Purpose: To evaluate the efficacy of SS-OCTA in the detection of silent CNV
secondary to chronic CSCR compared to that of FFA and SS-OCT. Patients and
Methods: A retrospective observational case series reviewing the clinical data,
FFA, SS-OCT, and SS-OCTA images of patients with chronic CSCR, and comparing the
findings. SS-OCTA detects the CNV complex and delineates it from the surrounding
pathological features of chronic CSCR by utilizing the blood flow detection
algorithm, OCTARA, and the ultrahigh-definition B-scan images of the retinal
microstructure generated by swept-source technology. The bivariate correlation
procedure was used for the calculation of the correlation matrix of the variables
tested. Results: The study included 60 eyes of 40 patients. Mean age was 47.6
years. Mean disease duration was 14.5 months. SS-OCTA detected type 1 CNV in 5
eyes (8.3%). In all 5 eyes, FFA and SS-OCT were inconclusive for CNV. The
presence of foveal thinning, opaque material beneath irregular flat PED, and
increased choroidal thickness in chronic CSCR constitutes a high-risk profile for
progression to CNV development. Conclusion: Silent type 1 CNV is an established
complication of chronic CSCR. SS-OCTA is indispensable in excluding CNV
especially in high-risk patients and whenever FFA and SS-OCT are inconclusive.
PMID- 29348932
TI - Long-Term Follow-Up in Children with Anisocoria: Cocaine Test Results and Patient
Outcome.
AB - Background: Evaluation of anisocoria including pharmacological testing for
Horner's syndrome in the pediatric population is challenging in view of potential
serious underlying disease. We describe cocaine test results, outcome of systemic
investigation, and long-term follow-up in children with anisocoria. Methods:
Retrospective review of medical records and phone interview of consecutive
pediatric patients (<18 years old) who underwent cocaine testing from August 2007
to July 2015 at a tertiary referral centre. Results: A total of 35 patients were
included with a positive, negative, or inconclusive cocaine test in 12/35, 19/35,
and 4/35, respectively. Systemic investigation was performed in 11 of the
patients with a positive and in 2 of the patients with an inconclusive cocaine
test result. Mediastinal Hodgkin lymphoma was found in one patient with an
inconclusive cocaine test result. Two other cases were presumably related to
birth trauma and surgical trauma. None of the other children further developed
any pathology during the follow-up period of 34.8 months (range 0-106.6).
Conclusions: In most children with anisocoria and a positive cocaine test result,
systemic investigation did not reveal any underlying etiology. The only malignant
disease was diagnosed in a patient with a suspicion of Horner's syndrome but with
an inconclusive cocaine test result in our cohort.
PMID- 29348933
TI - Prevalence and Associated Risk Factors of Hypertension: A Cross-Sectional Study
in Urban Varanasi.
AB - Hypertension is a major public health problem and important area of research due
to its high prevalence and being major risk factor for cardiovascular diseases
and other complications. Objectives. (1) To assess the prevalence of hypertension
and its associated factors and (2) to estimate awareness, treatment, and adequacy
of control of hypertension among study subjects. Methods and Materials. A
community based cross-sectional study with multistage sampling design was
conducted among urban population of Varanasi. A modified WHO STEPS interview
schedule on 640 study subjects aged 25-64 years was used. Results. The prevalence
of hypertension was 32.9% (male: 40.9%, female: 26.0%). Mean systolic and
diastolic BP were 124.25 +/- 15.05 mmHg and 83.45 +/- 9.49 mmHg, respectively.
Higher odds of being hypertensive were found in male subjects, eldest age group,
married subjects, subjects of upper socioeconomic status, illiterate subjects,
and retired subjects. Tobacco and alcohol consumption, overweight, obesity, and
abdominal obesity were also associated with hypertension. Out of the total
hypertensive 211 subjects, only 81 (38.4%) were aware about their hypertension
status; out of those, 57 (70.4%) were seeking treatment and 20 (35.08%) had their
blood pressure adequately controlled. Conclusion. Around one-third of the
subjects were hypertensive and half of the study subjects were prehypertensive in
this area. The awareness, treatment, and control of high blood pressure were also
very low.
PMID- 29348934
TI - "In Silico" Characterization of 3-Phytase A and 3-Phytase B from Aspergillus
niger.
AB - Phytases are used for feeding monogastric animals, because they hydrolyze phytic
acid generating inorganic phosphate. Aspergillus niger 3-phytase A (PDB: 3K4Q)
and 3-phytase B (PDB: 1QFX) were characterized using bioinformatic tools. Results
showed that both enzymes have highly conserved catalytic pockets, supporting
their classification as histidine acid phosphatases. 2D structures consist of 43%
alpha-helix, 12% beta-sheet, and 45% others and 38% alpha-helix, 12% beta-sheet,
and 50% others, respectively, and pI 4.94 and 4.60, aliphatic index 72.25 and
70.26 and average hydrophobicity of -0,304 and -0.330, respectively, suggesting
aqueous media interaction. Glycosylation and glycation sites allowed detecting
zones that can affect folding and biological activity, suggesting fragmentation.
Docking showed that H59 and H63 act as nucleophiles and that D339 and D319 are
proton donor residues. MW of 3K4Q (48.84 kDa) and 1QFX (50.78 kDa) is similar;
1QFX forms homodimers which will originate homotetramers with several catalytic
center accessible to the ligand. 3K4Q is less stable (instability index 45.41)
than 1QFX (instability index 33.66), but the estimated lifespan for 3K4Q is
superior. Van der Waals interactions generate hydrogen bonds between the active
center and O2 or H of the phytic acid phosphate groups, providing greater
stability to these temporal molecular interactions.
PMID- 29348935
TI - Effect of Male Involvement on the Nutritional Status of Children Less Than 5
Years: A Cross Sectional Study in a Rural Southwestern District of Uganda.
AB - Background: Undernutrition among children less than 5 years is still a public
health concern in most developing countries. Fathers play a critical role in
providing support in improving maternal and child health. There is little studied
on male involvement and its measurement in child nutrition; therefore, this paper
explores the level of male involvement in child feeding and its association with
the nutritional status of the children less than 5 years of age. Methods: A cross
sectional study among 346 households, 3 focus group discussions, and 4 key
informant interviews were conducted in one rural district in Uganda. Adjusted
odds ratios (aORs) and 95% confidence intervals (95% CI) of associated factors
were estimated and focus group discussions and in-depth interviews were conducted
and summarized into themes. Results: The study revealed the highest percentage of
the males provided money to buy food for the children (93.6%), and only 9.8% have
ever accompanied mothers to young child clinics. Conclusion: In this study, most
males were involved in buying food for their children, and providing money for
transport to young child clinics was associated with normal nutritional status of
children less than 5 years in the study area.
PMID- 29348936
TI - Guiding Inspiratory Flow: Development of the In-Check DIAL G16, a Tool for
Improving Inhaler Technique.
AB - Portable inhalers are divisible into those that deliver medication by patient
triggering (pMDIs: a gentle slow inhalation) and those that use the patient's
inspiratory effort as the force for deaggregation and delivery (DPIs: a stronger
deeper inspiratory effort). Patient confusion and poor technique are commonplace.
The use of training tools has become standard practice, and unique amongst these
is an inspiratory flow meter (In-Check) which is able to simulate the resistance
characteristics of different inhalers and, thereby, guide the patient to the
correct effort. In-Check's origins lie in the 1960s peak expiratory flow meters,
the development of the Mini-Wright peak flow meter, and inspiratory flow
assessment via the nose during the 1970s-1980s. The current device (In-Check DIAL
G16) is the third iteration of the original 1998 training tool, with detailed and
ongoing assessments of all common inhaler resistances (including combination and
breath-actuated inhaler types) summarised into resistance ranges that are preset
within the device. The device works by interpolating one of six ranges with the
inspiratory effort. Use of the tool has been shown to be contributory to
significant improvements in asthma care and control, and it is being advocated
for assessment and training in irreversible lung disease.
PMID- 29348937
TI - Work Change in Multiple Sclerosis as Motivated by the Pursuit of Illness-Work
Life Balance: A Qualitative Study.
AB - Individuals with multiple sclerosis have a tendency to make early decisions for
work change, even in reversible, episodic, or mild disease stages. To better
understand how a multiple sclerosis (MS) diagnosis influences perceptions of work
and motivations for work changes, we conducted a hermeneutic phenomenology study
to explore the work lives of ten individuals with MS in Malaysia. The
interpretive analysis and cumulative narratives depict an overarching change in
their concept of ideal work and life aspirations and how participants make
preemptive work changes to manage illness-work-life futures in subjectively
meaningful ways. Discussions on their integrated pursuit of finding dynamic and
subjective illness-work-life balance include reconciling the problem of hard work
and stress on disease activity and progress, making positive lifestyle changes as
health management behaviour, and the motivational influence of their own life and
family roles: the consideration of their spouses, parents, and children. At an
action level, work change was seen as moral and necessary for the management of
illness futures. Our findings contribute insights on how individual perceptions
and holistic life management decisions contribute to on-going and disrupted work
trajectories, which can inform practice and policy on early interventions to
support continued employment.
PMID- 29348938
TI - Treatment of Anemia of Chronic Disease with True Iron Deficiency in Pregnancy.
AB - Objective: We assess and compare the efficacy of anemia treatment in pregnant
women with anemia of chronic disease with true iron deficiency and in women with
iron deficiency anemia. Study Design: Fifty patients with moderate anemia
(hemoglobin 8.0-9.9 g/dl) and iron deficiency (ferritin < 15 MUg/l) were treated
in the Anemia Clinic at the Department of Obstetrics. Results: All patients
showed stimulation of erythropoiesis as evidenced by an increase in reticulocyte
count at day eight of therapy and showed an increase in hemoglobin and hematocrit
at the end of therapy (p < 0.001). The target hemoglobin (>=10.5 g/dl) was
achieved in 45/50 women (90%). 12 patients showed anemia of chronic disease with
true iron deficiency (12/50; 24%). Seven women (7/12; 59%) with anemia of chronic
disease and iron deficiency responded well to anemia treatment. 50% of women with
anemia of chronic disease and iron deficiency (3/6) responded well to intravenous
iron, and 67% (4/6) responded well to the combination of intravenous iron and
recombinant human erythropoietin. Conclusion: Because of frequent true iron
deficiency in pregnant women with anemia of chronic disease, anemia of chronic
disease in pregnancy is often falsely diagnosed as iron deficiency anemia.
PMID- 29348939
TI - Effect of Insoles with a Toe-Grip Bar on Toe Function and Standing Balance in
Healthy Young Women: A Randomized Controlled Trial.
AB - Objective: The aim of this randomized controlled study was to investigate the
effects of insoles with a toe-grip bar on toe function and standing balance in
healthy young women. Methods: Thirty female subjects were randomly assigned to an
intervention group or a control group. The intervention group wore shoes with
insoles with a toe-grip bar. The control group wore shoes with general insoles.
Both groups wore the shoes for 4 weeks, 5 times per week, 9 hours per day. Toe
grip strength, toe flexibility, static balance (total trajectory length and
envelope area of the center of pressure), and dynamic balance (functional reach
test) were measured before and after the intervention. Results: Significant
interactions were observed for toe-grip strength and toe flexibility (F = 12.53,
p < 0.01; F = 5.84, p < 0.05, resp.), with significant improvement in the
intervention group compared with that in the control group. Post hoc comparisons
revealed that both groups showed significant improvement in toe-grip strength (p
< 0.01 and p < 0.05, resp.), with higher benefits observed for the intervention
group (p < 0.01). Conversely, no significant interaction was observed in the
total trajectory length, envelope area, and functional reach test. Conclusions:
This study suggests that insoles with a toe-grip bar contribute to improvements
in toe-grip strength and toe flexibility in healthy young women.
PMID- 29348940
TI - Perceptions and Practices of the Iranian Population regarding Skin Cancers: A
Literature Review.
AB - Despite being preventable, more than 15% of all cancer cases in Iran occur in the
skin, making them the most commonly diagnosed malignancy in the country. The
purpose of this study is to gain an insight into the current skin cancer related
knowledge, attitudes, beliefs, and practices among the Iranian population. A
systematic computer based literature search was conducted using databases for
articles published through April 2017. Research studies included those that
measured skin cancer or sun protection related knowledge, attitudes, beliefs, and
behaviors in different Iranian population groups. Exclusion criteria for the
articles included (1) irrelevant topics to the review article's aim, (2) articles
that focused on the treatment of skin cancers instead of prevention practices,
and (3) similar studies conducted on populations not indigenous to Iran. A total
of 25 articles that met the eligibility criteria were included in the review.
Predominant data were collected via questionnaires. Skin cancer related knowledge
varied from low to high across the studies. Moreover, there was a pattern of low
perceived skin cancer susceptibility and severity. Overall, there was low usage
of sun protection methods among the Iranian population. The findings of this
study show that efforts to prevent skin cancer are needed. Education concerning
the dangers of sun exposure as well as strategies used to prevent or lower the
risk of developing skin cancer should be stressed.
PMID- 29348941
TI - The Immunoexpression of Glucocorticoid Receptors in Breast Carcinomas,
Lactational Change, and Normal Breast Epithelium and Its Possible Role in Mammary
Carcinogenesis.
AB - The role of estrogen and progesterone receptors in breast cancer biology is well
established. In contrast, other steroid hormones are less well studied.
Glucocorticoids (GCs) are known to play a role in mammary development and
differentiation; thus, it is of interest to attempt to delineate their
immunoexpression across a spectrum of mammary epithelia. Aim. To delineate the
distribution pattern of glucocorticoid receptors (GRs) in malignant versus
nonmalignant epithelium with particular emphasis on lactational epithelium.
Materials and Methods. Immunohistochemistry (IHC) for GRs was performed on
archival formalin-fixed paraffin-embedded tissue blocks of 96 cases comprising 52
invasive carcinomas, 21 cases with lactational change, and 23 cases showing
normal mammary tissue histology. Results. Results reveal an overexpression of GRs
in mammary malignant epithelium as compared to both normal and lactational groups
individually and combined. GR overexpression is significantly more pronounced in
HER-2-negative cancers. Discussion. This is the first study to compare GR
expression in human lactating epithelium versus malignant and normal epithelium.
The article discusses the literature related to the pathobiology of GCs in the
breast with special emphasis on breast cancer. Conclusion. The lactational
epithelium did not show overexpression of GR, while GR was overexpressed in
mammary NST (ductal) carcinoma, particularly HER-2-negative cancers.
PMID- 29348942
TI - Molecular Signatures of Radiation Response in Breast Cancer: Towards Personalized
Decision-Making in Radiation Treatment.
AB - Recent advances in gene expression profiling have allowed for a more
sophisticated understanding of the biology of breast cancers. These advances led
to the development of molecular signatures that now allow clinicians to more
individually tailor recommendations regarding the utility and necessity of
systemic therapies for women with breast cancer. Indeed, these molecularly based
tests have been incorporated into national and international best practice
guidelines and are now part of routine practice. Similar, though slower, progress
is being made in the development of molecular signatures predictive of radiation
response and necessity for women with breast cancer. This article will discuss
the history of radiation response signature development, the current state of
these signatures under ongoing clinical development, the barriers to their
clinical adoption, and upcoming changes and opportunities that may allow for the
personalized radiation treatment recommendations enabled by the development of
these signatures.
PMID- 29348943
TI - Interhemispheric Pathways Are Important for Motor Outcome in Individuals with
Chronic and Severe Upper Limb Impairment Post Stroke.
AB - Background: Severity of arm impairment alone does not explain motor outcomes in
people with severe impairment post stroke. Objective: Define the contribution of
brain biomarkers to upper limb motor outcomes in people with severe arm
impairment post stroke. Methods: Paretic arm impairment (Fugl-Meyer upper limb,
FM-UL) and function (Wolf Motor Function Test rate, WMFT-rate) were measured in
15 individuals with severe (FM-UL <= 30/66) and 14 with mild-moderate (FM-UL >
40/66) impairment. Transcranial magnetic stimulation and diffusion weight imaging
indexed structure and function of the corticospinal tract and corpus callosum.
Separate models of the relationship between possible biomarkers and motor
outcomes at a single chronic (>=6 months) time point post stroke were performed.
Results: Age (DeltaR20.365, p = 0.017) and ipsilesional-transcallosal inhibition
(DeltaR20.182, p = 0.048) explained a 54.7% (p = 0.009) variance in paretic WMFT
rate. Prefrontal corpus callous fractional anisotropy (PF-CC FA) alone explained
49.3% (p = 0.007) variance in FM-UL outcome. The same models did not explain
significant variance in mild-moderate stroke. In the severe group, k-means
cluster analysis of PF-CC FA distinguished two subgroups, separated by a
clinically meaningful and significant difference in motor impairment (p = 0.049)
and function (p = 0.006) outcomes. Conclusion: Corpus callosum function and
structure were identified as possible biomarkers of motor outcome in people with
chronic and severe arm impairment.
PMID- 29348945
TI - The Use of Adenosine to Enable Safe Implantation of Transcatheter Tricuspid
Valve.
AB - High precision is necessary during percutaneous transcatheter heart valve
implantation. The precision of the implantation has been established by
increasing the heart rate (usually to 200 beats per minute) to the point of
significantly reduced cardiac output and thus minimizing valve movement.
Routinely, this tachycardia is induced by rapid pacing. Here we report a case of
failure to pace during valve-in-valve (VIV) Edwards Sapien XT implantation in the
tricuspid valve position. Transient cardiac arrest was induced by intravenous
adenosine injection enabling accurate valve implantation.
PMID- 29348944
TI - A Longitudinal fMRI Research on Neural Plasticity and Sensory Outcome of Carpal
Tunnel Syndrome.
AB - Peripheral nerve compression is reported to induce cortical plasticity, which was
well pictured by former researches. However, the longitudinal changes brought by
surgical treatment are not clear. In this research, 18 subjects who suffered from
bilateral carpal tunnel syndrome were evaluated using task-dependent fMRI and
electromyography assessment before and after surgery. The third digit was
tactually simulated by von Frey filaments. The results demonstrated that the
pattern of activation was similar but a decreased extent of activation in the
postcentral gyrus, inferior frontal lobe, superior frontal lobe, and
parahippocampal gyrus after surgery was found. The correlation analysis showed a
significant correlation between the decreased number of activated voxels and the
improvement of EMG performance. This result implied a potential connection
between fMRI measurement and clinical improvement.
PMID- 29348946
TI - Group A Streptococci-Associated Necrotizing Fasciitis following Cat Bite in an
Immunocompromised Patient.
AB - Necrotizing soft tissue infections are characterized clinically by fulminant
tissue destruction, systemic signs of toxicity, and high mortality. Accurate
diagnosis and appropriate treatment must include early surgical intervention and
antibiotic therapy. Mortality rate is very high and could be even higher in an
immunocompromised host. We present a 57-year-old female with history of
rheumatoid arthritis on oral corticosteroid and methotrexate therapy with painful
swelling of the left hand following a cat bite that was diagnosed as having group
A streptococcus pyogenes-associated necrotizing fasciitis. Treatment with
ampicillin-sulbactam, Clindamycin, and surgical debridement was performed. In
spite of all the adequate therapy she succumbed to death from streptococcal toxic
shock and related complications after thirty-two days of treatment in intensive
care unit. Necrotizing fasciitis is an uncommon but life-threatening complication
in immunocompromised hosts. Tissue infections in cat bite wounds are commonly
caused by pathogenic bacterium known as Pasteurella multocida. Group A
streptococcal infections are not reported following cat bites. A high index of
suspicion must be maintained to suspect group A streptococcal associated
necrotizing fasciitis following cat bites and an early medical and surgical
intervention should be made for any best possible outcome.
PMID- 29348947
TI - Effects of Mifepristone on Nonalcoholic Fatty Liver Disease in a Patient with a
Cortisol-Secreting Adrenal Adenoma.
AB - Cushing syndrome (CS), a complex, multisystemic condition resulting from
prolonged exposure to cortisol, is frequently associated with nonalcoholic fatty
liver disease (NAFLD). In patients with adrenal adenoma(s) and NAFLD, it is
essential to rule out coexisting endocrine disorders like CS, so that the
underlying condition can be properly addressed. We report a case of a 49-year-old
woman with a history of hypertension, prediabetes, dyslipidemia, biopsy-confirmed
steatohepatitis, and benign adrenal adenoma, who was referred for endocrine work
up for persistent weight gain. Overt Cushing features were absent. Biochemical
evaluation revealed nonsuppressed cortisol on multiple 1-mg dexamethasone
suppression tests, suppressed adrenocorticotropic hormone, and low
dehydroepiandrosterone sulfate. The patient initially declined surgery and was
treated with mifepristone, a competitive glucocorticoid receptor antagonist. In
addition to improvements in weight and hypertension, substantial reductions in
her liver enzymes were noted, with complete normalization by 20 weeks of therapy.
This case suggests that autonomous cortisol secretion from adrenal adenoma(s)
could contribute to the metabolic and liver abnormalities in patients with NAFLD.
In conclusion, successful management of CS with mifepristone led to marked
improvement in the liver enzymes of a patient with long-standing NAFLD.
PMID- 29348948
TI - Granulomatous Pancreas: A Case Report of Pancreatic Sarcoid.
AB - Sarcoidosis is a chronic, systemic, noncaseating granulomatous disease process of
unknown etiology. Sarcoidosis most commonly manifests in the lungs; however,
gastrointestinal manifestations can occur. If in the GI tract, it is almost
always found in the liver. Solitary pancreatic lesions are extremely rare, with
less than 50 documented cases found in the literature. We present a case of a 61
year-old female, with a past medical history of sarcoidosis, who presented to the
ER with unexpected weight loss, scleral icterus, right upper quadrant pain, and
epigastric and back pain. US and MRI found a dilated common bile duct and mild
dilation of the pancreatic duct, as well as a focal prominence in the head of the
pancreas surrounded by areas of atrophy. A pancreaticoduodenectomy procedure was
performed and fresh frozen sections were taken. The pathologist made a diagnosis
of nonnecrotizing granulomatous pancreatitis. Pancreatic sarcoid is often
asymptomatic and a benign finding on autopsy; however, clinicians should be
mindful of pancreatic involvement when working up differential diagnosis for
pancreatic masses.
PMID- 29348949
TI - Cetuximab-Associated Crescentic Diffuse Proliferative Glomerulonephritis.
AB - Cetuximab-induced nephrotoxicity is very rare, occurring in less than 1% of
colorectal cancer patients and not defined in other populations. We report a rare
case of crescentic diffuse proliferative glomerulonephritis (GN) that developed
in close temporal association with cetuximab treatment. A 65-year-old female
recently completed chemotherapy with cetuximab treatment for moderately
differentiated oral squamous cell carcinoma. She was admitted with acute renal
failure and nephrotic-range proteinuria. Laboratory data showed serum creatinine
of 6.6 mg/dl and urinalysis showed proteinuria, moderate hemoglobinuria, hyaline
casts (41/LPF), WBC (28/HPF), and RBC (81/HPF). Serologic studies were negative
for ANA, anti-GBM, ANCA, hepatitis B, and hepatitis C. Serum C3 and C4 level were
normal. Renal biopsy showed crescentic diffuse proliferative GN with focal
features of thrombotic microangiopathy. Patient was started on cyclophosphamide
and steroids. Her renal function did not improve on day 8 and she was started on
hemodialysis. Previous reports suggest that EGFR-targeting medications can
possibly trigger or exacerbate an IgA-mediated glomerular process leading to
renal failure. This case suggests that cetuximab therapy may have triggered or
exacerbated a severe glomerular injury with an unfavorable outcome. Treating
physicians should maintain a high degree of caution and monitor renal function in
patients on EGFR inhibitors.
PMID- 29348950
TI - Carotid Endarterectomy in a Patient with Severe Internal Carotid Artery Stenosis
with Persistent Trigeminal Artery and Ischemia of the Anterior and Posterior
Circulation.
AB - Occurrence of cerebral ischemia in the posterior circulation as a result of
severe internal carotid artery disease and persistent trigeminal artery is rare.
An 81-year-old man with medical history of hypertension and ischemic stroke
presented with dizziness, nausea, and mild dysarthria. Magnetic resonance imaging
of the brain revealed acute infarcts in the left internal carotid artery
territory. CT angiogram revealed a persistent trigeminal artery (PTA) and severe
atherosclerosis. The patient developed new neurological symptoms and repeat
imaging revealed new acute infarcts in the PTA distribution. After undergoing a
left carotid endarterectomy with no complications, the patient was discharged to
a skilled nursing facility with no recurrence of ischemic stroke. This case adds
a rare complication of an infrequent vascular anomaly to the limited body of the
literature.
PMID- 29348951
TI - Prenatal Diagnosis of Thoracoschisis and Review of Literature.
AB - Thoracoschisis is a rare congenital malformation characterized by herniation of
the abdominal content through a defect in the thorax. There are previously 12
reported cases, most discussing the postnatal findings and management. Here we
describe a case of left thoracoschisis with associated upper limb abnormality
which was diagnosed antenatally with the aid of 3D ultrasound.
PMID- 29348952
TI - Persistent Corneal Decompensation due to Anterior Dislocation of Soemmering Ring
Cataract.
AB - Purpose: We present a case of a patient with Soemmering ring after cataract
surgery and a potential complication that can arise as a result of its presence.
Observations: A patient with history of ruptured globe status after repair and
lensectomy, complicated by aphakic secondary open angle glaucoma, was referred
for management of second injury to the same eye. This injury resulted in
Soemmering ring dislocation into the anterior chamber. The cortical material
caused a significant increase in intraocular pressure and corneal decompensation.
Surgical removal of the Soemmering ring and Ahmed glaucoma tube implant was
performed with control of intraocular pressures; however corneal edema could not
be reversed. Conclusions and Importance: This case report illustrates the serious
consequences that can be caused by Soemmering rings without early surgical
intervention. Care must be taken to completely remove cortical material during
cataract surgery to prevent their formation.
PMID- 29348953
TI - Multimodal Images of Acute Central Retinal Artery Occlusion.
AB - Two illustrative cases of acute central retinal artery occlusion (CRAO) are
presented with multimodal imaging, including fluorescein angiography (FA) and
commercially available optical coherence tomography angiography (OCT-A). In both
patients, retinal ischemia was imaged well using both FA and OCT-A, and the two
imaging studies provided comparable pictures. OCT-A provides useful information
for the diagnosis and management of patients with acute CRAO, without the need
for dye injection.
PMID- 29348954
TI - Managing an Acute and Chronic Periprosthetic Infection.
AB - A case report of a 65-year-old female with a history of right total hip
arthroplasty (THA) in 2007 and left THA in 2009 was presented. She consulted with
our institution for the first time, on December 2013, for right hip pain and
fistula on the THA incision. It was managed as a chronic infection, so a two
stage revision was performed. First-time intraoperative cultures were positive
for Staphylococcus aureus (3/5) and Proteus mirabilis (2/5). Three weeks after
the second half of the review, it evolved with acute fever and pain in relation
to right hip. No antibiotics were used, arthrocentesis was performed, and a
coagulase-negative staphylococci multisensible was isolated at the 5th day. Since
the germ was different from the first revision, it was decided to perform a one
stage revision. One year after the first review, the patient has no local signs
of infection and presents ESV and RPC in normal limits. The indication and
management of periprosthetic infections are discussed.
PMID- 29348955
TI - Pseudomonas aeruginosa Septic Arthritis and Osteomyelitis after Closed Reduction
and Percutaneous Pinning of a Supracondylar Humerus Fracture: A Case Report and
Review of the Literature.
AB - Infectious complications of closed reduction and percutaneous pinning of
supracondylar humerus fractures are exceedingly rare. Although postoperative
Pseudomonas infection is a feared complication associated with noncompliance and
a wet cast, there are no reports in the literature of this occurring. We present
the devastating complication of a pediatric patient who developed Pseudomonas
aeruginosa subperiosteal abscess, osteomyelitis, and elbow septic arthritis after
presenting to the clinic multiple times with a wet cast after closed reduction
and percutaneous pinning of a supracondylar humerus fracture. We describe the
treatment course for this patient, followed by the sequelae of posterolateral
rotary instability. This case not only confirms that patients can get Pseudomonas
infections if they get their cast wet but also stresses the importance of patient
communication and compliance in preventing unfortunate complications.
PMID- 29348956
TI - Nodular Lymphocyte-Predominant Hodgkin Lymphoma in Progressive Transformation of
Germinal Centers.
AB - Nodular lymphocyte-predominant Hodgkin lymphoma is an uncommon variant of Hodgkin
lymphoma. Progressive transformation of germinal centers has been associated with
and can develop prior to, concurrent with, or after the diagnosis of nodular
lymphocyte-predominant Hodgkin lymphoma. We present a patient with a history of
progressive transformation of germinal centers of the right parotid who presented
4 years later with ipsilateral parotid mass and cervical adenopathy. Knowledge of
her previous diagnosis raised our concern for lymphoma, influenced our surgical
management, and spared the patient additional surgery with risk of facial nerve
injury inherent in revision parotidectomy.
PMID- 29348957
TI - Acute Hematogenous Osteomyelitis in a Five-Month-Old Male with Rickets.
AB - Osteomyelitis is defined as an infection of the bone, bone marrow, and the
surrounding soft tissues. Most cases of acute hematogenous osteomyelitis in
children are caused by Gram-positive bacteria, principally Staphylococcus aureus.
We present a case where a 5-month-old male had an acute onset of decreased
movement of his left leg and increased irritability and was subsequently
diagnosed with rickets and hematogenous osteomyelitis with bacteremia. The case
explores a possible association between hematogenous osteomyelitis and rickets.
PMID- 29348958
TI - Seronegative Myasthenia Gravis, as a Rare Autoimmune Condition in Turner
Syndrome.
AB - Girls with Turner syndrome (TS), especially with isochromosome 46,X,i(X)(q10),
are prone to develop autoimmunity. Associations of several autoimmune conditions
with TS have been frequently described in the past. However, the unique
combination of TS and myasthenia gravis (MG) has been reported only once before
in a girl with mosaic monosomy 45,X/46,XX. Here, we present the second case of a
girl affected with seronegative MG but with mosaic isochromosome TS. This is a
child with developmental delay presented with muscle weakness, frequent fall, and
bilateral ptosis. Diagnosis of MG was made based on positive Tensilon and
electromyography tests and excellent response to intravenous immunoglobulin. At
the age of 11 years due to short stature and developmental delay, a karyotype was
done and revealed the mosaic isochromosome 45,X/46,X,i(X)(q10). Overall,
clinicians should be aware of the vulnerability of girls with TS to autoimmunity,
especially if the isochromosome 46,X,i(X)(q10) karyotype is identified.
Furthermore, if a child with TS develops muscle weakness, ptosis, or
ophthalmoplegia, MG should also be included in the differential diagnosis,
particularly if other concurrent autoimmune conditions are present.
PMID- 29348959
TI - Malignant Tumours Mimicking Complicated Appendicitis and Discovered upon Follow
Up after Percutaneous Drainage: A Case of Two Patients.
AB - The conservative management of periappendiceal abscesses is gaining favour due to
decreased morbidity and improved clinical outcomes for patients. Occasionally
however an abscess can mask underlying sinister pathology. In this article, we
highlight two cases of appendiceal adenocarcinoma that were initially diagnosed
as periappendiceal abscesses and managed conservatively with percutaneous
drainage. We also discuss clinical and imaging features that may assist with
identifying a hidden malignancy when presented in these situations.
PMID- 29348960
TI - Inflammatory Fibroid Polyp: An Unusual Cause of Ileoileal Intussusception.
AB - Inflammatory fibroid polyp (IFP), or Vanek's tumor, is a rare benign lesion of
the gastrointestinal tract. Clinical manifestations of IFP vary based on size and
location within the GI tract. This case describes a patient who presented with
hematochezia and abdominal pain. Computed tomography revealed ileoileal
intussusception without a clear lead point. The patient underwent resection of
the intussuscepted small bowel with primary anastomosis. A large polypoid mass
was identified as the pathological lead point. Histopathological and
immunohistochemical analysis revealed an IFP. Review of the literature indicates
that early surgical intervention is the treatment of choice for intussusception
caused by IFP. Lesions are typically reported as solitary, and resection is
curative.
PMID- 29348961
TI - Mesenchymal Hamartoma of the Liver: Complete Excision Always Necessary.
AB - Mesenchymal hamartoma (MH) is not an uncommon tumor of the liver in the age group
of 2-10 years. It is the second most common benign liver tumor in children.
Previously considered a developmental anomaly, newer insights into other theories
of origin including toxic-metabolic, ischemic, and a true neoplastic process are
in progress. Previous understanding of a purely benign nature of the tumor is
being overridden by a real malignant transformation. Complete excision of the
tumor with clear margins is recommended to achieve a long term cure. A thorough
understanding of the natural history of these tumors and skillful surgical
treatment are indispensable elements of care.
PMID- 29348962
TI - Primary Cytomegalovirus Infection Causing Guillain-Barre Syndrome in a Living
Renal Allograft Recipient.
AB - Guillain-Barre Syndrome (GBS) is a common acute autoimmune polyneuropathy in
adults. There have been few reported cases of Guillain-Barre Syndrome associated
with active cytomegalovirus (CMV) infection in renal transplant recipients. Here
we present a case of active CMV viremia inducing Guillain-Barre Syndrome in a
renal transplant recipient. We discuss the treatment regimen utilized.
Furthermore, we performed a review of the literature and discuss the cases of CMV
induced GBS in renal transplant recipients.
PMID- 29348963
TI - Mucin-Poor Mucinous Tubular and Spindle Cell Carcinoma of the Kidney Presented
with Multiple Metastases Two Years after Nephrectomy: An Atypical Behaviour of a
Rare, Indolent Tumour.
AB - Background: Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare type of
renal cell carcinoma, whose clinical behaviour and metastatic potential have not
been fully elucidated to date. There are only a few metastatic cases in the
literature, which all either featured sarcomatoid differentiation or were
synchronously metastasised at diagnosis. Case Presentation: We report a case of a
49-year-old male with end-stage kidney disease on dialysis, presenting with
multiple osseous metastases of a mucin-poor variant of MTSCC of the kidney,
without sarcomatoid differentiation, two years after bilateral nephrectomy for
papillary renal cell carcinoma (RCC) at a curable stage. After retrospectively
reexamining the initial nephrectomy specimens, the tumour of the right kidney was
also diagnosed as a mucin-poor variant of MTSCC, while the tumour of the left
kidney was confirmed as a papillary RCC. Conclusions: It is proposed that MTSCC
can be associated with end-stage renal disease and that particularly the mucin
poor variant is easily confused with papillary renal cell carcinoma, as happened
in this case. Although it is considered as a relatively indolent malign entity,
it can metastasise even years after successful primary surgical treatment. This
implies, besides accurate diagnosis, that MTSCC patients should be monitored
closely in the follow-up period.
PMID- 29348964
TI - Association between the APOE epsilon4 Allele and Late-Onset Alzheimer's Disease
in an Ecuadorian Mestizo Population.
AB - Alzheimer's disease (AD) is the most common neurodegenerative disease. It has two
main pathological hallmarks: amyloid plaques and neurofibrillary tangles. The
APOE epsilon4 allele has been recognized as the strongest genetic risk factor for
late-onset Alzheimer's disease (LOAD) in several populations worldwide, yet the
risk varies by region and ethnicity. The aims of this study were to describe APOE
allele and genotype frequencies and examine the relationship between the APOE
epsilon4 allele and LOAD risk in an Ecuadorian Mestizo population. We carried out
a case-control study comprising 56 individuals clinically diagnosed with probable
AD (>=65 years of age) and 58 unrelated healthy control subjects (>=65 years of
age). Genotyping was performed using the real-time PCR method. Our data showed
that allelic and genotypic frequencies follow the trends observed in most
worldwide populations. We also found a high-risk association between APOE
epsilon4 allele carriers and LOAD (OR = 7.286; 95% CI = 2.824-18.799; p < 0.001).
Therefore, we concluded that APOE epsilon4 must be considered an important
genetic risk factor for LOAD in the Ecuadorian Mestizo population. Additionally,
we suggest that in mixed populations the effects of admixture and ethnic identity
should be differentiated when evaluating genetic contributions to Alzheimer's
disease risk.
PMID- 29348965
TI - Ethanol-Induced Alterations of T Cells and Cytokines after Surgery in a Murine
Infection Model.
AB - Background: Interactions between alcohol, infection, and surgery and their effect
on differentiation and functionality of T helper cells are not yet completely
understood. We hypothesized that alcohol and surgery disturb differentiation of T
helper cells and contribute to an impaired immune response. Methods: Mice were
treated with alcohol for two weeks. Saline treatment served as control. Clinical
performance and weight were assessed. On day 14, a median laparotomy was
performed and animals were challenged with Klebsiella pneumoniae intranasally.
Bacterial load was determined in lungs and blood. T helper cell subpopulations
and the released cytokines were assessed in lungs, spleens, and plasma. Key
transcription factors of T cell differentiation were evaluated. Results: Alcohol
significantly impaired clinical appearance and body weight of animals with
postsurgical infection (p < 0.05). Bacterial load was significantly higher after
alcohol treatment (p < 0.05). T helper cell subsets and released cytokine levels
were significantly altered in lung, but not in spleen. Expression of
transcription factors of T helper cell lineage commitment did not translate into
different counts of T helper cells. Conclusions: Alcohol and surgery lead to
significant cellular and functional modulations of T helper cells during
postsurgical infection. These effects may contribute to an impaired immune
response after surgery.
PMID- 29348966
TI - Development of an Analytical Protocol for Determination of Cyanide in Human
Biological Samples Based on Application of Ion Chromatography with Pulsed
Amperometric Detection.
AB - A simple and accurate ion chromatography (IC) method with pulsed amperometric
detection (PAD) was proposed for the determination of cyanide ion in urine,
sweat, and saliva samples. The sample pretreatment relies on alkaline digestion
and application of Dionex OnGuard II H cartridge. Under the optimized conditions,
the method showed good linearity in the range of 1-100 MUg/L for urine, 5-100
MUg/L for saliva, and 3-100 MUg/L for sweat samples with determination
coefficients (R) > 0.992. Low detection limits (LODs) in the range of 1.8 MUg/L,
5.1 MUg/L, and 5.8 MUg/L for urine, saliva, and sweat samples, respectively, and
good repeatability (CV < 3%, n = 3) were obtained. The proposed method has been
successfully applied to the analysis of human biological samples.
PMID- 29348967
TI - Quantitative Aspect of Leucophyllum frutescens Fraction before and after
Encapsulation in Polymeric Nanoparticles.
AB - The interest on plants has been focalized due to their biological activities.
Extracts or fractions from plants in biodegradable polymeric nanoparticles (NP)
provide many advantages on application studies. The encapsulation of the extract
or fraction in NP is determined for the establishment of the test dose. HPLC
method is an alternative to calculate this parameter. An analytical method based
on HPLC for quantification of a hexane fraction from L. frutescens was developed
and validated according to ICH. Different concentrations of the hexane fraction
from leaves (HFL) were prepared (100-600 MUg/mL). Linearity, limit of detection,
limit of quantification, and intra- and interday precision parameters were
determined. HFL was encapsulated by nanoprecipitation technique and analyzed by
HPLC for quantitative aspect. The method was linear and precise for the
quantification of the HFL components. NP size was 190 nm with homogeneous size
distribution. Through validation method, it was determined that the encapsulation
of components (1), (2), (3), and (4) was 44, 74, 86, and 97%, respectively. A
simple, repeatable, and reproducible methodology was developed for the propose of
quantifying the components of a vegetable material loaded in NP, using as a model
the hexane fraction of L. frutescens leaves.
PMID- 29348968
TI - Evaluation of Root Canal Morphology of Mandibular First and Second Premolars
Using Cone Beam Computed Tomography in a Defined Group of Dental Patients in
Iran.
AB - Background: Successful dental root canal treatments require a complete knowledge
of dental anatomy and root canal morphology. Materials and Methods: One hundred
and forty-five cone beam computed tomography (CBCT) images were used to assess
the anatomy and morphology of mandibular premolars based on Vertucci's
classifications in a defined group of dental patients in Iran. The number of
roots and root canals, root canal morphology, root and canal shape (curvature),
existence of C-shaped canal, and influence of sex on each of these were
evaluated. A chi-squared test was used for statistical analysis. Results: The
mandibular first and second premolars had a single root in 95.97% and 100% cases,
respectively. In the mandibular first premolars, 62.2% were of type I, 0.8% type
II, 10.9% type III, 0.8% type IV, 20.3% type V, 4.2% type VI, and 0.8% type VII;
in the second premolars, 78% of canals were of type I, 3% type II, 11% type III,
7% type V, and 1% type VI. C-shaped canals did not exist in either of the
premolars. The most prevalent root and canal shape was straight. The most
prevalent root curvature was a distal curvature in both premolars (71.4% and 74%
of first and second premolars, resp.). The most prevalent canal curvature was
lingual and buccal for the first premolars (7.6% each) and distal for the second
premolars (11%). No significant difference was found between men and women in
nearly all of the above (P > 0.05). Conclusion: The results suggest that there is
a need to conduct further evaluations on finding root and canal variations among
more populations to gain better knowledge prior to root canal treatment.
PMID- 29348969
TI - Smallholder Farmers' Livelihood Security Options amidst Climate Variability and
Change in Rural Ghana.
AB - Farming as a livelihood activity in the Bosomtwe District is threatened by
climate change. This paper ascertained the alternative livelihood options of
smallholder farmers against climate variability and change in the Bosomtwe
District. Using a cross-sectional survey, 152 smallholder farmers were sampled
from 12 communities using a multistage sampling procedure. The quantitative data
collected were subjected to binary logistic regression analysis, contingency
tables, frequencies, and Nagelkerke tests of association, embedded in the
statistical package for social sciences (SPSS) v.17. The results indicate that
farmers are resorting to alternative livelihood activities that are less capital
intensive and require less skill in order to secure income and household food
supply. Significant determinants of farmers' alternative livelihood are age,
household size, and household food supply, which were significant at p < .030, p
< .019, and p < .012, respectively. At a 95% confidence interval (CI), these
variables had lower to upper CIs for each of the EXP (B), respectively, at CI =
1.134-12.524, CI = 1.359-30.224, and CI = 1.781-104.561, respectively. The paper
recommends that government institutes policies that will create opportunities and
draw on various local/grassroots opportunities and resources to expand farmers'
asset base for sustainable livelihood strategies.
PMID- 29348970
TI - Genetic Variability of Exotic Sugarcane Genotypes.
AB - Sugarcane is the main sugar producing crop in Bangladesh. However, improvement of
this crop through breeding is limited due to lack of genetic diversity.
Therefore, genetic variability and diversity assessment are necessarily important
for the foreign introduced materials. Experiment was conducted with 9 exotic
sugarcane genotypes at Regional Station, Bangladesh Sugar Crop Research
Institute, Gazipur, during 2012-13, following RCBD. Data were collected on
different growth and yield contributing characters. Individual cane weight
exhibited high genotypic coefficient of variation and phenotypic coefficient of
variation. Leaf blade length, leaf blade width, fresh leaf weight, dried leaf
weight, number of tillers, millable cane, bud size, cane diameter, internodes
number, internode length, plant height, stalk length, brix%, and individual cane
weight showed high heritability. Individual cane weight showed highly significant
and positive correlation with cane diameter, internode length, and stalk length,
whereas path coefficient analysis revealed that cane diameter had maximum
positive direct effect on individual cane weight followed by internode length,
number of tillers, and chlorophyll content. Results indicate that the genotypes
should be selected on the basis of individual cane weight, cane diameter, and
millable canes number for future breeding to get higher sugarcane yield in
respect to juice and brix content.
PMID- 29348971
TI - Ejection fraction improvement and reverse remodeling achieved with
Sacubitril/Valsartan in heart failure with reduced ejection fraction patients.
AB - BACKGROUND: Sacubitril/Valsartan has been shown to improve mortality and reduce
hospitalizations in patients with heart failure with reduced ejection fraction
(HFrEF). The effect of Sacubitril/Valsartan on ejection fraction (EF) and reverse
remodeling parameters have not been previously described. METHODS: We performed a
single-center, retrospective, cohort study of HFrEF patients (n=48) who were
treated with Sacubitril/Valsartan for a median duration of 3 months
(Interquartile range 2-6 months). Clinical and echocardiographic parameters were
reviewed at three time points (pre-baseline which was median of 18 months before
starting Sacubitril/Valsartan, baseline before treatment started, and post
Sacubitril/Valsartan). Paired sample t-test and one-way repeated measures ANOVA
were used for normally distributed data, while Wilcoxon Signed Rank test for non
normally distributed data. RESULTS: Sacubitril/Valsartan use was associated with
an average 5% (+/-1.2) increase in EF, from a mean baseline of 25.33% to 30.14%
(p<0.001) with a median duration of treatment 3 months. There was no significant
change in mean LVEF over a median duration of 11 months (IQR 5.5-15.5) between
pre-baseline and baseline time points prior to treatment (p=1.0). The mean
increase in ejection fraction tended to be marginally greater in the medium/high
dose cohort as compared to the low dose cohort, with a mean increase of 5.09% (+/
1.36) and 4.03% (+/-3.17), respectively (p=0.184). There was a 3.36 mm reduction
in left ventricular end-systolic diameter (p=0.04), a 2.64 mm reduction in left
ventricular end-diastolic diameter (p=0.02), and a 14.4 g/m2 reduction in left
ventricular mass index (p<0.01). CONCLUSION: Sacubitril/Valsartan was found to
improve EF and multiple measures of reverse remodeling beyond the effects of
concomitant optimal medical therapy. Though these results are encouraging, our
small sample, observational study requires confirmation in larger cohorts with
longer follow-up periods.
PMID- 29348972
TI - Galectin-3 and the incidence of abdominal aortic aneurysm: the atherosclerosis
risk in communities (ARIC) study.
AB - Galectin-3, a beta-galactosidase binding lectin, known to be involved in
inflammatory processes may be associated with abdominal aortic aneurysm (AAA)
incidence. We examined the prospective association between plasma galectin-3 and
incident AAA in 9,704 participants of the Atherosclerosis Risk in Communities
(ARIC) study cohort. We followed participants from 1996-1998 through 2011
(124,260 person-years) for incident AAA (n=325) defined by ICD codes from
hospital records and death certificates. At baseline, participants had a mean
(SD) age of 62.8 (5.7) years; 20.9% were blacks and 56.5% females. The median
(25th-75th percentile) galectin-3 level was 14.2 (12.0-16.9) ng/mL. Galectin-3
was correlated positively with most cardiovascular risk factors and with several
cardiac or inflammatory biomarkers (C-reactive protein, troponin-T, and NT
proBNP). Using Cox proportional hazards regression adjusted for demographic
variables and measured AAA risk factors, the hazard ratios for AAA across
galectin-3 quintiles were 1 (Referent), 1.54 (1.05-2.26), 1.58 (1.05-2.41), 1.76
(1.15-2.72), and 1.92 (1.22-3.01) (p for trend =0.01). Further adjustment for the
cardiac and inflammatory biomarkers largely attenuated the association between
galectin-3 and AAA [AAA hazard ratio for galectin-3 Quintile 5 vs. Quintile 1:
1.29 (0.81-2.05); p-trend across quintiles =0.44]. In conclusion, higher
concentrations of plasma galectin-3 were associated with greater incidence of AAA
though not independent of other cardiac and inflammatory biomarkers. This
reinforces that galectin-3, a systemic biomarker reflecting inflammation and
probably increased systemic vascular resistance, is elevated early in the
pathogenesis of AAA.
PMID- 29348973
TI - Associations between four types of single-nucleotide polymorphisms in PLA2G7 gene
and clinical atherosclerosis: a meta-analysis.
AB - BACKGROUND: Previous studies suggested that some types of single nucleotide
polymorphisms (SNPs) in PLA2G7 genes, encoding Lp-PLA2 have been reported to
yield an antiatherogenic effect, but other studies mentioned otherwise. Thus, a
comprehensive study to explore the effect of SNPs in PLA2G7 genes (V279F, A379V,
R92H, I198T) toward clinical atherosclerosis is needed. METHODS: We searched
eligible studies from PubMed, EBSCO, ProQuest, Science Direct, Springer, and
Cochrane databases for case-control studies to assess the between four types of
SNPs in PLA2G7 gene with risk of clinical atherosclerosis (CVD = cardiovascular
disease, CAD = coronary artery disease, PAD = peripheral artery disease, ischemic
stroke). All studies were assessed under Hardy-Weinberg Equilibrium, an additive
model. This meta-analysis was performed by RevMan 5.3 to provide pooled estimate
for odds ratio (ORs) with 95% confidence intervals (95% CIs). RESULTS: Fourteen
clinical studies met our inclusion criteria. Those included 12,432 patients with
clinical atherosclerosis and 10,171 were controls. We found that ORs of two
variants SNPs (V279F, R92H) were associated with clinical atherosclerosis {V279F,
OR = 0.88 (95% CI, 0.81-0.95); p = 0.0007, I2 = 40%}, {R92H, OR = 1.29 (95% CI,
1.09-1.53); p = 0.003, I2 = 73%}. Meanwhile, there was no significant
associations between the other two, A379V {OR = 1.08 (95% CI, 0.93-1.26); p =
0.31, I2 = 78%} and I198T {OR = 1.12 (95% CI = 0.79-1.59); p = 0.53, I2 = 81%}.
CONCLUSIONS: These results suggested that V279F polymorphism in PLA2G7 gene has a
protective effect for clinical atherosclerosis, whereas R92H polymorphism might
contribute toward increased risk of clinical atherosclerosis.
PMID- 29348974
TI - Systemic inhibition of neddylation by 3-day MLN4924 treatment regime does not
impair autophagic flux in mouse hearts and brains.
AB - Beyond helping the cell survive from energy starvation via self-eating a portion
of cytoplasm, macroautophagy is also capable of targeted removal of defective
organelles or cytoplasmic aberrant protein aggregates, thereby playing an
important role in quality control in the cell. Impaired or suppressed
macroautophagy activity is associated with the progression from a large subset of
heart diseases to heart failure and with the development of the vast majority of,
if not all, neurodegenerative diseases, the leading causes of death and
disability in humans. Hence, a better understanding of the impact of existing and
upcoming pharmacotherapies on macroautophagy in the heart and brain will
undoubtedly benefit the search for safer and more effective treatment to improve
human health. Neddylation is a recently recognized posttranslational modification
process that modifies a subset of cellular proteins and is, by virtue of
regulating Cullin-RING ligases, essential to ~20% ubiquitin-proteasome system
(UPS)-mediated protein degradation. MLN4924 (Pevonedistat), a specific inhibitor
of neddylation that promises to become a new anti-malignancy agent, is capable of
inhibiting UPS-mediated progression of the cell cycle and activating
macroautophagy in cancer cells. However, no reported study has tested the impact
of systemic inhibition of neddylation on autophagic activity in a post-mitotic
organ such as the heart and brain. This study was conducted to fill this gap.
Sixteen GFP-LC3 transgenic mice of mixed sexes were divided equally into either
MLN4924-treated or vehicle-treated groups and were treated respectively with
MLN4924 (30 mg/kg, s.c., twice a day * 3 days) or equal volume of solvent. The
resultant changes in myocardial levels of neddylated cullin 1 as well as
autophagic flux in cardiac and brain tissues were assessed. The effectiveness of
the MLN4924 regime was verified by myocardial accumulation of neddylated cullin
1. Myocardial LC3-II flux and free GFP levels were comparable between the MLN4924
and the vehicle groups whereas the protein level of p62, a bona fide substrate of
macroautophagy, in the brain was significantly decreased by the MLN4924
treatment. Our data suggest that systemic inhibition of neddylation by a 3-day
MLN4924 treatment regime does not suppress macroautophagy activities in the heart
and brain.
PMID- 29348975
TI - Some different treatment of sandal burns of the hand in children.
AB - The hands account for less than 5% of total body surface area, but loss of the
hand constitutes a 57% loss of function for the whole person. In Central Asia,
and particularly in Uzbekistan, many episodes of burns take place at homes
because of using sandal heaters. During a 16-year period (1992-2007), 61 patients
with severe sandal burns of the hand were treated at the Burn department of
RSCUMA and Samarkand Inter-Regional Burn Center, Uzbekistan. The main goal of
this work was to present the most complete information about sandal burns of the
hand and discuss the most effective methods of treatment for sandal burns. As a
result of using this method of treatment for burned children in our practice, the
percentage of post burn consequences, such as the impact on mobility and growth
of the extremities, was greatly reduced.
PMID- 29348977
TI - Treatment in the healing of burns with a cold plasma source.
AB - A cold plasma produced with helium gas was applied to two second-degree burns
produced with boiling oil. These burns were located on a thigh and a shin of a 59
years-old male person. After the first treatment as benefit the patient neither
presented itching nor pain and, after the second treatment, the patient presented
new tissue. This result opens the possibilities of the application of a cold
plasma source to health burns.
PMID- 29348976
TI - The validity and reliability of using ultrasound elastography to measure
cutaneous stiffness, a systematic review.
AB - BACKGROUND: Ultrasound elastography is an imaging technology which can
objectively and non-invasively assess tissue stiffness. It is emerging as a
useful marker for disease diagnosis, progression and treatment efficacy.
OBJECTIVE: To examine current, published research evaluating the use of
ultrasound elastography for the measurement of cutaneous or subcutaneous
stiffness and to determine the level of validity and reliability, recommended
methodologies and limitations. METHODS: MEDLINE, Web of science and Scopus were
systematically searched in August 2016 to identify original articles evaluating
the use of ultrasound elastography to assess cutaneous stiffness. Relevant
studies were then quality evaluated using the Quality Assessment of Diagnostic
Accuracy Studies v 2 (QUADAS-2) tool and the Quality Appraisal of Reliability
Studies (QAREL). RESULTS: From a total of 688 articles, 14 met the inclusion
criteria for full review. Within the 14 studies, elastography was used to
evaluate tumors, systemic sclerosis, lymphedema, abscess, and post-radiation neck
fibrosis. Only three robust studies demonstrated good interrater reliability,
whereas all validity studies had low sample sizes and demonstrated risks of bias.
CONCLUSION: Robust evidence supporting the use of ultrasound elastography as a
diagnostic tool in cutaneous conditions is low, however, initial indicators
support further research to establish the utility of ultrasound elastography in
dermatology.
PMID- 29348978
TI - The effect of ambient lighting on Laser Doppler Imaging of a standardized
cutaneous injury model.
AB - OBJECTIVE: The aim of this study was to investigate the potential confounding
effects of four different types of ambient lighting on the results of Laser
Doppler Imaging (LDI) of a standardized cutaneous injury model. METHODS: After
applying a mechanical stimulus to the anterior forearm of a healthy volunteer and
inducing a wheal and arteriolar flare (the Triple response), we used a Laser
Doppler Line Scanner (LDLS) to image the forearm under four different types of
ambient lighting: light-emitting-diode (LED), compact fluorescent lighting (CFL),
halogen, daylight, and darkness as a control. A spectrometer was used to measure
the intensity of light energy at 785 nm, the wavelength used by the scanner for
measurement under each type of ambient lighting. RESULTS: Neither the LED nor CFL
bulbs emitted detectable light energy at a wavelength of 785 nm. The color-based
representation of arbitrary perfusion unit (APU) values of the Triple response
measured by the scanner was similar between darkness, LED, and CFL light.
Daylight emitted 2 mW at 785 nm, with a slight variation tending more towards
lower APU values compared to darkness. Halogen lighting emitted 6 mW of light
energy at 785 nm rendering the color-based representation impossible to
interpret. CONCLUSIONS: Halogen lighting and daylight have the potential to
confound results of LDI of cutaneous injuries whereas LED and CFL lighting did
not. Any potential sources of daylight should be reduced and halogen lighting
completely covered or turned off prior to wound imaging.
PMID- 29348979
TI - Simplified estimation of binding parameters based on image-derived reference
tissue models for dopamine transporter bindings in non-human primates using
[18F]FE-PE2I and PET.
AB - The aim of this study on dopamine transporter binding by [18F]FE-PE2I and PET was
to describe an image-derived approach using reference tissue models: the Logan
DVR approach and simplified reference tissue model (SRTM), the features of which
were simple to operate and precise in the measurements. Using the approach, the
authors sought to obtain binding images and parameters. [18F]FE-PE2I and dynamic
PET as well as an MRI was performed on three rhesus monkeys, and metabolite
corrected arterial plasma inputs were obtained. After co-registering of PET to MR
images, both image sets were resliced. The time-activity curve of the cerebellum
was used as indirect input, and binding parametric images were computed voxel-by
voxel. Voxel-wise linear calculations were used for the Logan DVR approach, and
nonlinear least squares fittings for the SRTM. To determine the best linear
regression in the Logan DVR approach, the distribution volume ratio was obtained
using the optimal starting frame analysis. The obtained binding parameters were
compared with those obtained by the other independent ROI-based numerical
approaches: two-tissue compartment model (2TCM), Logan DVR approach and SRTM
using PMOD software. Binding potentials (BP) obtained by the present approach
agreed well with those obtained by ROI-based numerical approaches, although
reference tissue models tended to underestimate the BP value than 2TCM. Image
derived Logan approach provided a low-noise image, the computation time was
short, and the error in the optimal starting frame analysis was small. The
present approach provides a high-quality binding parametric image and reliable
parameter value easily.
PMID- 29348980
TI - The value of FDG PET/CT for follow-up of patients with melanoma: a retrospective
analysis.
AB - The incidence of melanoma (MM) is among the fastest rising cancers in the western
countries. Positron Emission Tomography with Computed Tomography (PET/CT) is a
valuable non-invasive tool for the diagnosis and staging of patients with MM.
However, research on the value of PET/CT in follow-up of melanoma patients is
limited. This study assesses the diagnostic value of PET/CT for follow-up after
melanoma surgery. This retrospective study includes patients with MM who
performed at least one PET/CT scan after initial surgery and staging. PET/CT
findings were compared to histology, MRI or fine needle aspiration (FNA) to
estimate the diagnostic accuracy. The diagnostic performance of PET/CT performed
in patients with and without a clinical suspicion of relapse was compared. 238
patients (526 scans) were included. Of the 526 scans 130 (25%) scans were PET
positive, 365 (69%) PET-negative, and 28 (5%) had equivocal findings. Sensitivity
was 89% [0.82-0.94], specificity 92% [0.89-0.95], positive and negative
predictive values of 78% [0.70-0.84] and 97% [0.94-0.98] respectively. When
stratified for reason of referral there was no statistical significant difference
in the diagnostic accuracy of PET/CT between patients referred with or without a
clinical suspicion of relapse. This study demonstrates that PET/CT despite a
moderate sensitivity has a high negative predictive value in the follow-up of
melanoma patients. Thus, a negative PET/CT-scan essentially rules out relapse.
However, the frequency of false positive findings is relatively high, especially
among patients undergoing a "routine" PET/CT with no clinical suspicion of
relapse, potentially causing anxiety and leading to further diagnostic
procedures.
PMID- 29348981
TI - Development of a clinically feasible [11C]PE2I PET method for differential
diagnosis of parkinsonism using reduced scan duration and automated reference
region extraction.
AB - [11C]PE2I is a highly selective dopamine transporter PET ligand. Parametric
images based on dynamic [11C]PE2I scans, showing dopamine transporter
availability (BPND) and relative cerebral blood flow (R1), can be used in
differential diagnosis of parkinsonism. This work aimed to investigate a
shortened scan duration and automated generation of parametric images which are
two prerequisites for routine clinical application. Twelve subjects with
parkinsonism and seventeen healthy controls underwent 80 min dynamic [11C]PE2I
PET scans. BPND and R1 images were generated using cerebellum reference region
defined on a co-registered MRI, as well as a supervised cluster analysis (SVCA)
based reference. Initial 20, 30 and 40 min of the scans were extracted and images
of standardized uptake value ratio (SUVR) and R1 were computed using MRI- and
SVCA-based reference. Correlation was high between striatal 80 min MRI-based BPND
and 40 min SVCA-based SUVR-1 (R2=0.95). High correlation was also found between
R1 values in striatal and limbic regions (R2>=0.91) whereas correlation was
moderate for cortical regions (R2=0.71). The results indicate that dynamic
[11C]PE2I scans can be restricted to 40 min and that SVCA can be used for
automatic extraction of a reference region. These outcomes will support routine
applications of [11C]PE2I PET in clinical settings.
PMID- 29348982
TI - Pictorial atlas of symptomatic accessory ossicles by 18F-Sodium Fluoride (NaF)
PET-CT.
AB - Accessory ossicles are developmental variants which are often asymptomatic. When
incidentally picked up on imaging, they are often inconsequential and rarely a
cause for concern. However, they may cause pain or discomfort due to trauma,
altered stress, and over-activity. Nuclear scintigraphy may play a role in the
diagnosis and localizing pain generators. 18F-Sodium Fluoride (NaF) is a PET
imaging agent used in bone imaging. Although commonly used in imaging patients
with cancer imaging malignancy, 18F-NaF may be useful in the evaluation of benign
bone and joint conditions. In this article, we would like to present a spectrum
of clinical cases and review the potential diagnostic utility of 18F-NaF in the
assessment of symptomatic accessory ossicles in patients referred for staging
cancers.
PMID- 29348983
TI - Sparse domain approaches in dynamic SPECT imaging with high-performance
computing.
AB - Iterative reconstruction algorithms often have relatively large computation time
affecting their clinical deployment. This is especially true for 4D
reconstruction in dynamic imaging (DI). In this work, we have shown how sparse
domain approaches and parallelization for static 3D image reconstruction and 4D
dynamic image reconstruction (directly from sinogram) in Single Photon Emission
Computed Tomography (SPECT), without any intermediate 3D reconstructions, can
improve computational efficiency. DI in SPECT is one of the hardest inverse
problems in medical image reconstruction area and slow reconstruction is a
challenge for this promising protocol. Our work hopefully, paves a new direction
toward making DI in SPECT clinically viable. Our 4D reconstruction also is a
novel application of non-negative matrix factorization (NNMF) in an inverse
problem.
PMID- 29348984
TI - Human immune system during sleep.
AB - A joint function of tissues, organs and cells for the protection of body develops
immune system. The human immune response against various infections during sleep,
its mechanism, neuroimmune interactions, immunoregulatory effect of sleep along
with sleep deprivation and role of cytokines in sleep deprivation were addressed.
It is revealed that human immune system and sleep both are associated and
influenced by each other. Sleep deprivation makes a living body susceptible to
many infectious agents. In the result, immune system of human body is altered by
releasing immunomodulators in the response of infections as reported by various
researchers. Basic reasons and mechanisms of most of the poor sleep networks and
release of proinflammatory modulators are still uncertain. The current situation
requires improved sleep habits to make immune system efficient for a healthy
life.
PMID- 29348985
TI - The effect and safety of diacerein in patients with type 2 diabetes mellitus : a
systematic review and meta-analysis.
AB - : The Background: Diacerein has been proposed as a treatment option for
management of type 2 diabetes due to its anti-inflammatory properties. PURPOSE:
The aim of this systematic review and meta-analysis of randomized controlled
trials (RCTs) is to examine the effect and safety of diacerein in patients with
type 2 diabetes. DATA SOURCES AND STUDY SELECTION: We searched Pubmed, Embase,
and Cochrane Library for RCTs published from database inception to September
2017. DATA EXTRACTION AND DATA SYNTHESIS: Among 44 studies that were initially
identified, four were eligible and were included in the following analysis.
Diacerein significantly reduced fasting glycemia [weighted mean differences (WMD)
-0.66, 95% confidence interval (95% CI) -1.16 to -0.16] and glycated hemoglobin
A1c (HbA1c ) (WMD -0.85, 95% CI -1.44 to -0.26). And the patients with a
diacerein supplementation duration of <=12 weeks had a greater decrease of
fasting glycemia and HbA1c than the supplementation duration of >12 weeks.
Furthermore, compared with placebo, diacerein revealed a significant increase in
the relative risk (RR) of gastrointestinal symptoms (RR=2.50, 95% CI: 1.10 to
5.65), especially in the study subgroup with supplementation duration of >12
weeks (RR=4.01, 95% CI: 2.32 to 6.95). LIMITATIONS: The sample size was
relatively small and the duration of included studies was short so that the
treatment efficacy and safety for longer duration was unknown. CONCLUSIONS:
Although further studies are needed, our findings clearly provide support to the
use of diacerein in the clinical management of subjects with type 2 diabetes.
PMID- 29348986
TI - An immunohistochemical analysis of folate receptor beta expression and
distribution in giant cell arteritis - a pilot study.
AB - BACKGROUND: Giant cell arteritis (GCA) is a chronic vasculitis of large and
medium vessels in which no targetable biomarkers exist to allow selective
treatment, predict disease activity and monitor therapeutic responses. The
accessibility of the temporal artery (TA) for biopsy allows morphologic studies
to characterize macrophages and T cells in the microenvironment of the arterial
wall. We evaluated the expression of folate receptor beta (FRB), a candidate
diagnostic/therapeutic biomarker, compared its expression with key macrophage
markers and correlated it with GCA severity. METHODS: Formalin-fixed paraffin
embedded tissue sections were examined from 6 patients with GCA and 2 controls.
Immunohistochemistry was performed using FRB, ETB, CD68 and CD3 antibodies to
evaluate for activated macrophages and T cells, assess FRB distribution along the
intima, media and adventitial layers and composition of inflammatory infiltrates.
We compared the expression of FRB, ETB and CD68 in GCA versus negative controls
and in severe (with visual loss) versus mild (without visual loss) disease.
RESULTS: In GCA, moderate to severe inflammation was accompanied by >90%
destruction of the internal elastic lamina. Macrophages comprised 36.3 +/- 4.1%
while CD3+ lymphocytes accounted for 61.7 +/- 4.1% of total leukocytes. FRB was
selectively expressed in macrophages and localized to the adventitia. GCA
patients had marginally increased median FRB (9.8 cells/hpf vs. 0; p=0.095), ETB
(20.5 vs. 0; p=0.095) and CD68 (38.8 vs. 5; p=0.071) expression versus controls.
ETB was found in endothelial cells, smooth muscle cells and macrophages in
intima/media. FRB positively correlated with ETB (r=0.90; p-0.037) and CD68
levels (r=0.90; p=0.037). ETB expression positively correlated with CD68 (r=1.0;
p<0.0001). There was no difference in FRB between severe and mild GCA.
CONCLUSION: FRB is a potential diagnostic and therapeutic biomarker with
restricted expression in GCA macrophages. FRB+ macrophages localized to the
adventitia and their expression correlated with ETB and CD68 macrophages,
suggesting that they contribute to GCA pathogenesis.
PMID- 29348987
TI - Rhino-Orbital-Cerebral Mucormycosis: A Fatal Complication of Uncontrolled
Diabetes Mellitus.
AB - Mucormycosis is a progressively invasive disease, with a fatal outcome, on late
presentation. A 38-year-old female presented with diabetic ketoacidosis with
right eye ptosis and a frozen globe without any signs of inflammation,
externally. She underwent transnasal endoscopic debridement of paranasal sinuses
and exenteration of the right eye. The histopathology specimen revealed the
growth of mucormycosis. She was treated with intravenous (IV) amphotericin B, IV
insulin, and extensive debridement surgery, but had an unfavorable outcome due to
rapid mucor invasion to the brain.
PMID- 29348988
TI - Anal Squamous Cell Carcinoma in a Patient with Myasthenia Gravis: Is
Immunosuppression the Main Underlying Etiology?
AB - Patients who are immunocompromised by diseases such as human immunodeficiency
virus (HIV) infection are more prone to develop some malignancies such as
Kaposi's sarcoma and central nervous system (CNS) lymphomas. Historically, anal
squamous cell carcinoma (SCC) was also included on the list as an acquired
immunodeficiency syndrome (AIDs)-defining cancer. Similarly, compromised immune
disorders including severe immunosuppression, haematologic malignancies, and
solid organ transplantation have been identified as important risk factors for
the development of anal SCC. Review of the medical literature showed only
sporadic cases of anal SCC in patients with pre-existing myasthenia gravis (MG),
with or without thymoma. We present here a case of anal SCC in a patient with
several years history of MG who was receiving intravenous immunoglobulin (IVIG).
We believe this association is explained by the autoimmune nature of the disease
and the use of immunosuppressive medications to treat it. To further support our
case, we also present a review of the literature associating anal SCC with MG.
PMID- 29348989
TI - Signs and Symptoms of Acoustic Neuroma at Initial Presentation: An Exploratory
Analysis.
AB - Introduction The objective of this study was to describe the most common clinical
features associated with an acoustic neuroma diagnosis and to identify those
features associated with larger tumour size at initial diagnosis. Methods The
clinical information of 945 consecutive patients diagnosed with acoustic neuroma
at a single centre between 1992 and 2015 was analysed. Clinical features were
examined and the relationship between these features and tumour size (>2.5 cm)
was analysed using descriptive statistics and logistic regression analysis.
Statistical analysis was performed in R version 3.1.1. Results The most common
presenting symptom was a unilateral hearing loss in 752 patients (80%), with a
progressive pattern in 90% of these cases. The second most common presenting
symptom was unilateral tinnitus, accounting for 6.3%, while ataxia, vertigo and
headache accounted for 3.8%, 3.4% and 2%, respectively. The diagnosis of acoustic
neuroma was an incidental finding in 20 patients (2.1%). Temporal analysis
demonstrated a downward trend in the number of patients presenting with hearing
loss and an increased proportion of patients presenting with other symptoms. On
multivariate analysis, larger tumour size was associated with abnormal tandem
gait (odds ratio 8.9, p=0.02), subjective facial weakness (odds ratio 5.3, p<
0.001), abnormal facial sensation on examination (odds ratio 3.0, p=0.03) and
headache (odds ratio 2.6, p< 0.001). Conclusion The majority of patients with
acoustic neuroma present with the classic, progressive, unilateral hearing loss.
However, the pattern of presentation in acoustic neuroma patients is changing.
Features in the history indicative of a larger tumour are headaches and
subjective facial weakness, whilst concerning features on examination are
abnormal tandem gait and altered facial sensation.
PMID- 29348990
TI - Hypercalcemia of Malignancy: An Emergency Medicine Simulation.
AB - Hypercalcemia is a poor prognostic factor associated with malignancy. The signs
and symptoms of hypercalcemia that the patients present to the emergency
department are vague and often overlap with the general symptoms of cancer itself
or the adverse effects of the chemotherapy. Given that the development of
hypercalcemia of malignancy can present with imminent danger to the patient and
is a treatable condition, emergency physicians should know how to recognize and
treat it. It also marks a time at which discussions regarding plans of care
should be initiated with the patients. In this report, we describe a simulation
case that can be used to train emergency medicine residents to both recognize and
treat hypercalcemia of malignancy and to initiate the discussion of goals of
care.
PMID- 29348991
TI - Medical Expulsive Therapy for Distal Ureteral Stones: Tamsulosin Versus Silodosin
in the Turkish Population.
AB - Introduction Our aim was to contribute a study that includes a higher patient
population to the limited number of studies comparing tamsulosin and silodosin in
the treatment of distal ureteral stones. Material and methods Patients who
presented with renal colic to the urology emergency clinic and were diagnosed
with ureteral stones and followed-up with conservative treatment between January
2010 and January 2016 were retrospectively screened. According to the inclusion
exclusion criteria, the patients were divided into three groups. Group 1: 150
patients followed with watchful waiting (WW), Group 2: 156 patients who received
0.4 mg of tamsulosin daily, and Group 3: 159 patients who received 8 mg of
silodosin daily. The side effects of the used drugs, duration of stone reduction,
and expulsion rates were evaluated and compared separately. Results A total of
465 patients were included in the study. No statistically significant difference
was found in terms of age, gender, and stone size among the groups. The patient
characteristics and results are shown in Table 1. The differences in stone
expulsion rate between the groups in the first week were calculated using the Chi
square test and found to be non-significant (p = 0.155); whereas, the stone
expulsion rates between Group 1 versus Group 2 and Group 1 versus Group 3 were
found to be significantly different after the second and third week. Conclusion
According to our results, no statistically significant superiority between
tamsulosin and silodosin was shown in the treatment of distal ureteral stones in
the Turkish population.
PMID- 29348992
TI - Hernioscopy in Incarcerated Inguinal Hernia Spontaneously Reduced after General
Anesthesia Induction.
AB - Hernioscopy is essentially hernia sac laparoscopy. Hernia repair has evolved over
the years with better outcomes; however, strangulated inguinal hernias are acute
surgical emergencies which require emergent operative intervention. During
anesthesia induction and/or after incision, hernia self-reduction is possible,
with or without compromised bowel, back into the abdominal cavity. It is pivotal
to examine the bowel to decide on further operative course. A simple alternative
to unnecessary laparotomy or standard laparoscopy is hernioscopy, which is quite
uncommon. We present a case of an acute symptomatic strangulated left-sided
inguinal hernia which got self-reduced during anesthesia induction and was
successfully repaired after hernioscopy was used to evaluate the incarcerated
hernia content. We provide a brief review of literature about hernioscopy and an
algorithm to guide surgeons in emergent cases.
PMID- 29348993
TI - Delayed Presentation of Cerebral Air Embolism from a Left Atrial-Esophageal
Fistula: A Case Report and Review of the Literature.
AB - Air embolism developing from an atrial-esophageal fistula that was created as a
complication from an atrial ablation procedure is a rare, yet usually fatal
diagnosis. Neurologic manifestations such as meningitis, altered mental status,
seizures, strokes, transient ischemic attacks (TIAs), psychiatric changes, and
coma can ensue. Imaging of the brain might reveal infarcts, cerebral edema, as
well as signs of pneumocephalus. This case describes a 42-year-old male with
recent cardiac ablation procedure at an outside hospital for refractory atrial
fibrillation (A-fib) who presented with altered mental status, dyspnea and
diaphoresis. His initial head computed tomography (CT) scan revealed
pneumocephalus. He was started on a heparin drip for a non-ST elevation
myocardial infarction (NSTEMI), but developed severe coagulopathy. The patient's
mental status quickly deteriorated. Given recent cardiac ablation procedure, the
cause of his air embolism was thought to be from a created left atrial-esophageal
fistula. Despite medical management, he was too unstable to undergo any surgical
intervention for his atrial-esophageal fistula or to transfer to a hyperbaric
oxygen therapy center, and expired on the second day following his hospital
admission. To our knowledge, few reports have been published in the literature
describing delayed cerebral air embolism from an atrial-esophageal fistula.
Prompt diagnosis, hyperbaric oxygen therapy, and surgical intervention are
essential to avoid mortality in these patients. This article aims to increase
awareness of such a rare, but significant complication.
PMID- 29348994
TI - The association of Mediterranean diet and exercise modifications with
anthropometric parameters in a psychiatric community population: A pilot study.
AB - Weight gain and related metabolic syndrome (MS) are major current issues in
public health. MS consists of abdominal fat, atherogenic dyslipidemia,
hypertension, hyperglycemia, insulin resistance, pro-inflammatory and pro
thrombotic state, and accounts for both cardiovascular diseases and type II
diabetes mellitus risk factors. Patients affected by psychiatric illness present
a prevalence of 35-40% of MS. Many studies have shown that Mediterranean diet is
associated with the reduction of mortality due to cardiovascular and malignant
diseases, potentially preventing both obesity and type II diabetes mellitus. Our
pilot study explores the effects of a 12-month healthy lifestyle program
(Mediterranean diet and mild physical activity) on metabolic and anthropometric
parameters of patients affected by chronic psychiatric disorders who live in a
psychiatric community facility. A Mediterranean diet was provided by a senior
nutritional clinician and adapted by two dieticians, according to the needs and
preferences of the community population. Concomitantly, a program of moderate
physical activity, consisting in 30-min walks on level ground 4 days a week, and
psycho-educational group sessions with educational and therapeutic purposes were
implemented. The metabolic and anthropometric parameters of our patients improved
after both 6 (T6) and 12 (T12) months. Body Max Index was statistically
significantly reduced at T6 and T12, with patients perceiving good quality of
life. These positive outcomes suggest that a low-cost healthy lifestyle program
can produce good adherence and feasibility even among patients with chronic
psychiatric diseases, reducing their risk for MS, cardiovascular diseases and
other complications.
PMID- 29348995
TI - Mental health assessment in health checks of participants aged 30-49 years: A
large-scale cohort study.
AB - Mental distress is an independent risk factor for illness related impairment.
Awareness of mental health (MH) allows prevention, but early detection is not
routinely performed in primary care. This cohort study incorporated MH assessment
in a health promoting programme. We described the level of poor MH among health
check participants, explored the potential for early intervention, and the
potential for reducing social inequality in MH. The study was based on 9767
randomly selected citizens aged 30-49 years invited to a health check in Denmark
in 2012-14. A total of 4871 (50%) were included; 49% were men. Poor MH was
defined as a mental component summary score of <= 35.76 in the SF-12 Health
Survey. Data was obtained from national health registers and health check.
Participants with poor MH (9%) were more socioeconomic disadvantaged and had
poorer health than those with better MH. Two thirds of men (64%) and half of
women (50%) with poor MH had not received MH care one year before the health
check. Among those with (presumably) unrecognized MH problems, the proportion of
participants with disadvantaged socioeconomic characteristics was high (43-55%).
Four out of five of those with apparently unacknowledged poor MH had seen their
GP only once or not at all during the one year before the health check. In
conclusion, MH assessment in health check may help identify yet undiscovered MH
problems.
PMID- 29348996
TI - Acculturation and dietary intake pattern among Jamaican immigrants in the US.
AB - Information on dietary intakes of Jamaican immigrants in the United States is
sparse. Understanding factors that influence diet is important since diet is
associated with chronic diseases. This study examined the association between
acculturation, socio-cultural factors, and dietary pattern among Jamaican
immigrants in Florida. Jamaican persons 25-64 years who resided in two South
Florida counties were recruited for participation. A health questionnaire that
assessed acculturation, dietary pattern, and risk factors for cardiovascular
disease was administered to participants. Generalized Estimating Equations were
used to determine associations. Acculturation score was not significantly
associated with dietary intake pattern (beta = - 0.02 p = 0.07). Age at migration
was positively associated with traditional dietary pattern (beta = 0.02 p <
0.01). Persons with 12 or fewer years of education (beta = - 0.55 p < 0.001),
divorced (beta = - 0.26 p = 0.001), or engaged in less physical activity (beta =
0.07 p = 0.01) were more likely to adhere to a traditional diet. Although
acculturation was not a statistically significant predictor of dietary intake,
findings show the role of demographic and lifestyle characteristics in
understanding factors associated with dietary patterns among Jamaicans. Findings
point to the need to measure traditional dietary intakes among Jamaicans and
other immigrant groups. Accurate assessment of disease risk among immigrant
groups will lead to more accurate diet-disease risk assessment and development of
effective intervention programs.
PMID- 29348997
TI - Diagnosis and management of a fatal case of sepsis caused by Candida parapsilosis
sensu stricto in a neonate with omphalocele.
AB - We present a fatal case of persistent neonatal candidemia by Candida parapsilosis
following omphalocele, without other anomalies. Despite an encouraging initial
prognosis, after surgical correction and closure of the abdominal wall the case
became difficult to treat, as in addition to the exposure of the patient to
multiple risk factors for candidemia, antifungal therapy apparently was not
adequate.
PMID- 29348998
TI - Meniscal Repair With Fibrin Clot Augmentation.
AB - Meniscal injuries and meniscal loss are associated with changes in knee
kinematics and loading, ultimately leading to poor functional outcomes and
increased risk of progression to osteoarthritis. Biomechanical studies have shown
restored knee function, and clinical studies have reported improved outcomes and
decreased risk of osteoarthritis after meniscal repair. This has led orthopaedic
surgeons to try and save the meniscus by repair whenever possible, as shown by
increasing incidence of meniscal repair surgeries. Historically, meniscal
lesions, particularly those greater in size and located in the white-white region
of the meniscus, have been shown to have poor healing. In recent years, there has
been an increasing interest in the use of biologic agents to help stimulate and
expedite healing in traditionally more avascular tissue. Preliminary results for
biologic therapeutic agents, such as platelet rich plasma and bone marrow
aspirate concentrate, have been encouraging. However, these options are more
demanding in regard to time, financial burden, resources, and regulations than
some more classic agents such as fibrin clots. Fibrin clot is readily available,
easy to use, affordable, and minimally invasive. This Technical Note describes a
step-by-step and reproducible technique for harvesting, preparation, and using a
fibrin clot to augment healing of meniscal repairs.
PMID- 29348999
TI - Open Repair of Quadriceps Tendon With Suture Anchors and Semitendinosus Tendon
Allograft Augmentation.
AB - Quadriceps tendinopathy in an increasingly recognized diagnosis can lead to
quadriceps tendon rupture, especially in the older population. It can be caused
by repeated micro trauma or also predisposed by systemic diseases such as
diabetes mellitus and connective tissue disorders that can in turn lead to
extensor mechanism deficits. Although a trial of conservative treatment is
advocated, operative treatment should be performed in cases of persistent pain,
extension deficit, or complete rupture of the tendon. The purpose of this
Technical Note is to describe in detail a procedure for open repair of a
quadriceps tendon, with significant degeneration due to quadriceps tendinopathy,
using suture anchors and semitendinosus tendon allograft augmentation.
PMID- 29349000
TI - Hamstring Graft Preparation Techniques for Anterior Cruciate Ligament
Reconstruction.
AB - Anterior cruciate ligament reconstruction is one of the most commonly performed
procedures in orthopaedics, with more than 125,000 performed in the United States
per year. There are several reconstruction graft choices that can be used to
reconstruct the native anterior cruciate ligament, with autograft hamstring
tendons being one of the most commonly used. Preparation of a hamstring autograft
varies depending on patient characteristics and physician preference. The purpose
of this Technical Note is to describe in detail different variants of hamstring
graft preparation techniques that are commonly used in practice.
PMID- 29349001
TI - Medial Closing-Wedge Distal Femoral Osteotomy with Medial Patellofemoral Ligament
Imbrication for Genu Valgum with Lateral Patellar Instability.
AB - A varus-producing distal femoral osteotomy (DFO) is an effective technique for
the treatment of lateral patellar instability (LPI) in patients with concomitant
moderate to severe valgus malalignment. Patellar maltracking and subluxation are
corrected via neutralization of some of the laterally directed forces on the
patella due to the valgus deformity. This can be accomplished with a distal
femoral lateral opening-wedge or medial closing-wedge osteotomy and medial soft
tissue stabilization. A medial closing-wedge osteotomy offers the advantages of
immediate weight bearing and a single incision in cases requiring patellofemoral
soft tissue stabilization. In this article, we describe our preferred operative
technique for a medial closing-wedge DFO using a femoral locking plate and medial
patellofemoral ligament imbrication for the correction of LPI.
PMID- 29349002
TI - Medial Patellofemoral Ligament Reconstruction Using Dual Patella Docking
Technique.
AB - Medial patellofemoral ligament (MPFL) injuries are common in children and young
adults. In patients with recurrent patellar dislocations with normal lower
extremity alignment, anatomic reconstruction of the MPFL has been shown to
restore patellar stability. We describe a technique that creates an anatomic
reconstruction using a dual docking technique into the patella. Our technique is
simple and efficacious for reconstructing the MPFL without implant fixation in
the patella, allowing a maximal bone-tendon interface for healing.
PMID- 29349003
TI - Arthroscopic Anterior Shoulder Stabilization With Incorporation of a Comminuted
Bony Bankart Lesion.
AB - Bony Bankart lesions are a common finding in patients with anterior glenohumeral
dislocation. Although there are no defined guidelines, small bony Bankart
fractures are typically treated arthroscopically with suture anchors. The 2 main
techniques used are double- and single-row suture anchor stabilization, with
debate over superiority. Biomechanical studies have shown improved reduction and
stabilization with the double-row over the single-row suture anchor technique;
however, this has not been reported for small or comminuted bony fragments. Both
techniques have shown promising preliminary clinical outcomes. In this Technical
Note, we describe our preferred technique for arthroscopic instability repair
using a single-row all-suture anchor method with the incorporation of a
comminuted bony Bankart fragment in the lateral decubitus position.
PMID- 29349004
TI - Arthroscopic Treatment of a Malunion of a Posteromedial Tubercle Fracture of the
Talus.
AB - Posteromedial ankle impingement is rare and uncommonly associated with a
fracture. Bone resection of the fragment is the recommended treatment. In this
report, we describe the step-by-step surgical technique of arthroscopic resection
of a malunion of a posteromedial talus fracture to correct the impingement.
PMID- 29349005
TI - Arthroscopic Elbow Osteocapsular Arthroplasty.
AB - Treatment of primary elbow osteoarthritis in the young active patient less than
50 years old presents a treatment challenge to the practicing orthopaedic
surgeon. Following failure of nonoperative management, surgical goals are aimed
at reducing pain and improving joint mobility from bony impingement. Arthroscopic
osteocapsular arthroplasty is a viable treatment option with few post-operative
limitations. In contrast, total elbow arthroplasty is considered a salvage option
in this patient population given the activity restrictions imposed. Osteocapsular
arthroplasty combines soft tissue and bony debridement, osteophyte/loose body
removal, synovectomy, capsular release, and bony contouring of the humerus and
ulna to allow impingement-free range of motion.
PMID- 29349006
TI - Simultaneous Bilateral Knee Valgus Stress Radiographic Technique.
AB - The medial collateral ligament is the most commonly injured knee ligament. Valgus
stress radiographs are reported to be an effective way to quantify the medial
compartment opening. However, most of the techniques require the presence of a
physician in the radiograph room to apply a manual valgus stress force, and can
only be performed in 1 knee at a time. These techniques, although extremely
effective, increase radiation exposure to physicians, are time consuming, and
require additional radiographs to compare the side-to-side difference. The
purpose of this Technical Note is to describe our preferred valgus stress
radiographic technique to evaluate medial side laxity, which offers several
advantages compared with conventional manual techniques.
PMID- 29349007
TI - Anterior Cruciate Ligament Primary Repair With Independent Tensioning of the
Anteromedial and Posterolateral Bundles.
AB - This procedure represents an update on traditional primary repair methods by
taking advantage of technological advancements to optimize soft tissue fixation
and allow for an anatomic double-bundle primary repair with independent bundle
tensioning and an internal brace construct to restore normal anterior cruciate
ligament biomechanics.
PMID- 29349008
TI - Meniscal Allograft Transplantation Made Simple: Bridge and Slot Technique.
AB - Over recent years, appreciation for the critical role of the meniscus in joint
biomechanics has led to an emphasis on meniscal preservation. Meniscal allograft
transplant (MAT) is a promising biological solution for the symptomatic young
patient with a meniscus-deficient knee that has not developed advanced
osteoarthritis. As surgical techniques are refined and outcomes continue to
improve, it is vital to consider the utility of such procedures and offer a
straightforward approach to MAT. This article and accompanying video provide a
step-by-step tutorial on how to perform a MAT using the bridge and slot
technique, its key pearls and pitfalls as well as the relevant advantages and
disadvantages of MAT.
PMID- 29349009
TI - Arthroscopic Repair of Type II SLAP Tears Using Suture Anchor Technique.
AB - Arthroscopic SLAP tear repair has become an increasingly used treatment for
patients presenting with symptomatic SLAP tears after failed nonoperative
management. Debridement, SLAP repair, and open or arthroscopic biceps tenodesis
or tenotomy have been used for the treatment of SLAP tears. Various techniques
for repair have been described, and furthermore, there is a high incidence of
concomitant pathology of the shoulder. Repair remains an excellent option in
isolated SLAP tears amenable to repair, with excellent outcomes in well-indicated
patients. We present a method for repairing a SLAP tear using standard suture
anchor fixation, anterior and posterior portals, and an accessory portal of
Wilmington. Adequate labral repair can be achieved with this technique in
patients with no concomitant biceps pathology. This report highlights this
technique for SLAP repair in patients with isolated symptomatic SLAP tears that
have failed conservative management.
PMID- 29349010
TI - Arthroscopic Repair of Hip Labrum With Suture Anchors.
AB - The acetabular labrum and the transverse acetabular ligament form a continuous
ring of tissue on the periphery of the acetabulum that provides a seal for the
hip joint and increases the surface area to spread load distribution during
weight-bearing. When a labral tear is suspected, the treatment algorithm always
begins with conservative management, including physical therapy and nonsteroidal
anti-inflammatory drugs. When conservative management fails, patients become
candidates for arthroscopic labral repair. In the last 2 decades, the rate of hip
arthroscopy has increased nearly 4-fold. However, as hip arthroscopy is performed
more frequently, there is a need for a proper technique to minimize morbidity,
because hip arthroscopy has been known to have a steep learning curve. We present
a method for arthroscopic hip labral repair using suture anchors without a
capsular repair. This Technical Note highlights our technique for labral repair,
along with pearls and pitfalls of hip arthroscopy.
PMID- 29349011
TI - Middle Glenohumeral Ligament Abrasion Causing Upper Subscapularis Tear.
AB - The middle glenohumeral ligament (MGHL) typically contributes partially to the
anterior stability of the shoulder. In a very limited number of cases, the MGHL
can cause abrasion on the upper edge of the subscapularis causing persistent pain
symptoms for patients. The condition is exacerbated by internal rotation of the
arm. In this Technical Note, we describe this entity and call it the SAM lesion
(Subscapularis Abrasion from the MGHL). We present a technique of addressing this
lesion.
PMID- 29349012
TI - Arthroscopic Reduction and Internal Fixation of a Rim Fracture.
AB - Femoroacetabular impingement is uncommonly associated to a rim fracture. Complete
resection of the fragment might result in iatrogenic instability or poor femoral
head coverage. In this report, we describe the step-by-step surgical technique of
arthroscopic partial resection of a rim fracture, reduction and internal fixation
of the remaining fragment to correct the impingement, and preserve the adequate
acetabular coverage.
PMID- 29349013
TI - Open-Wedge Valgus High Tibial Osteotomy Technique With Inverted L-Shaped
Configuration.
AB - High tibial osteotomy (HTO) is a useful alternative in the treatment of
symptomatic varus malalignment. However, among its drawbacks is the tendency to
decrease patellar height and increase the posterior tibial slope. The increased
tibial slope increases anterior cruciate ligament tension and may compromise its
function. On the other hand, patella baja often causes anterior knee pain and,
over time, may favor degeneration of the patellofemoral joint. The aim of this
study is to describe a technical modification of the standard open-wedge HTO. It
consists of a double inverted L-shaped cut, which includes the anterior tibial
tuberosity in the proximal fragment, to avoid any alteration of patellar height
and control the eventual increase of the posterior tibial slope.
PMID- 29349014
TI - Graft Preparation Technique to Optimize Hamstring Graft Diameter for Anterior
Cruciate Ligament Reconstruction.
AB - Hamstring autografts are frequently used for anterior cruciate ligament
reconstruction. The inherent variability in graft diameter has been stated as a
disadvantage in its use because the presence of smaller graft diameters has been
correlated with increased risk of re-rupture. Several techniques have been
described to address this concern. Modifications of the basic Graftlink technique
allows for increased control over final graft diameter using a standard harvest
of the semitendinosus tendon with or without the gracilis tendon, and results in
a graft of adequate length and diameter in all patients with rigid cortical
fixation on the femur and tibia.
PMID- 29349015
TI - Patellar Tendon Repair With Ipsilateral Semitendinosus Autograft Augmentation.
AB - Patellar tendon ruptures are rare but potentially devastating injuries. Acute
repair after patellar tendon rupture affords the best opportunity for tension
free restoration of the extensor mechanism. Biological augmentation of primary
repair is believed to decrease strain across the repair site and reduce the risk
of rerupture. We present a technique for primary patellar tendon repair with
bidirectional fixation using transosseous tunnels, suture anchor fixation, and
ipsilateral hamstring autograft augmentation in a distal patellar pole socket.
PMID- 29349016
TI - The External Rotation Radiographic Technique for Posterolateral Injury.
AB - Posterolateral corner injuries are a severe and often unrecognized pathology.
Injuries to these structures are difficult to identify using magnetic resonance
images. Physical examination tests including the dial test, frog-leg test, and
varus stress test can be difficult to perform. In addition it is difficult to
correctly evaluate the results in a multiligament injury setting. The correct
diagnosis of this pathology is essential to determine the proper treatment and
improve outcomes. Furthermore, failure to recognize this pathology is associated
with a high risk of failure following isolated anterior cruciate ligament
reconstructions. The purpose of this Technical Note is to present an alternative
method for the evaluation of posterolateral corner injuries using radiographic
images.
PMID- 29349017
TI - Simultaneous Radiographic Technique to Evaluate Ankle Instability.
AB - The use of ankle stress radiographs is common to evaluate ankle instability.
However, the majority of the studies report the use of a manual method to apply
the stress, increasing radiation exposure to the physician. Furthermore, as
reported in other studies, the force applied during the stress may vary between
examiners according the strength and experience. In this Technical Note, we
describe our preferred method to evaluate ankle instability, either using an
inversion or eversion stress, avoiding the necessity of a physician in the
radiographic room.
PMID- 29349018
TI - Open 4-Compartment Fasciotomy for Chronic Exertional Compartment Syndrome of the
Leg.
AB - Chronic exertional compartment syndrome (CECS) is a significant source of lower
extremity pain and morbidity in the athletic population. Although endoscopic
techniques have been introduced, open fasciotomy remains the mainstay of surgical
treatment because of the paucity of evidence in support of an endoscopic
approach. The literature on surgical management of CECS is mixed, and overall
success rates are modest at best. Optimizing surgical technique, including
prevention of neurovascular injury and wound complications, can make a
significant impact on the clinical outcome. Here we present our surgical
technique, including pearls and pitfalls, for open 4-compartment fasciotomy for
treatment of chronic exertional compartment syndrome.
PMID- 29349019
TI - Arthroscopic Decompression of Greater Trochanteric Sciatic Nerve Impingement.
AB - Therapeutic extra-articular hip endoscopy is an effective treatment of greater
trochanteric sciatic nerve impingement. We describe in detail technical pearls of
the procedure including positioning, portal placement, and steps to obtaining
adequate decompression while avoiding iatrogenic nerve injury.
PMID- 29349020
TI - An Arthroscopic Humeral Medializing Repair of the Supraspinatus.
AB - Posterosuperior repair of the rotator cuff is one of the most frequently
performed surgical procedures in the shoulder. Its aim is to fix the tendon back
to the bone to restore anatomy, improve shoulder function, and prevent
progression of cuff tear arthropathy and attendant muscle degeneration. Despite
technical advances in this procedure, in some cases, the tendon cannot be fixed
back to the footprint without excessive tension on the repair. In young patients
or in patients with low-grade muscle atrophy and fatty degeneration (Goutallier
grade 1 or 2), it is mandatory to attempt fixation of the tendon to restore
functional anatomy and prevent further muscle degeneration. In such cases, an
arthroscopic medialized reinsertion of the supraspinatus may be considered. We
describe an arthroscopic humeral medializing repair of the supraspinatus tendon
that allows for a tension-free repair of the supraspinatus using common portals
and instruments. The goal of this technique is to obtain tendon healing, restore
functional anatomy, and prevent atrophy and fatty degeneration of the muscles of
the rotator cuff.
PMID- 29349021
TI - Arthroscopic Repair of Medial Transtendinous Rotator Cuff Tears.
AB - Rotator cuff tears are extremely common in the adult population, and medial
transtendinous rotator cuff tears, although rare, have recently been reported in
the literature. These tears are almost always traumatic, which is a common
indication for surgical management. It is necessary to consider these tears as a
distinct subset when planning for rotator cuff repair because traditional repair
techniques would overtension the tendon, increasing the risk for failure of the
repair. The objective of this Technical Note is to describe an arthroscopic
repair technique for these tears that avoids overtensioning the rotator cuff
while still using repair techniques that are familiar to the arthroscopic
shoulder surgeon.
PMID- 29349022
TI - Arthroscopic Delivery of Injectable Bone Graft for Staged Revision Anterior
Cruciate Ligament Reconstruction.
AB - Bone defects caused by femoral and tibial tunnel enlargement can pose a
significant technical challenge when planning to perform revision anterior
cruciate ligament reconstruction. A number of options have been described for
managing osseous deficiencies, including the use of large autograft or allograft
bone dowels to provide sufficient tunnel fill and subsequent structural support
for revision surgery. These techniques can be time-consuming and technically
demanding to ensure proper tunnel fill and press-fit stability of the bone graft.
We describe our preferred technique for arthroscopic bone grafting using a
mixture of demineralized cortical bone graft augmented with platelet-rich plasma
delivered through a simple delivery system.
PMID- 29349023
TI - Bipolar Acromioclavicular Joint Resection.
AB - Acromioclavicular (AC) joint arthropathy remains one of the most common causes of
shoulder pain. In the case of AC joint arthropathy resistant to conservative
treatment, most authors have recognized distal clavicle resection as the gold
standard treatment. However, some challenges remain to be solved. One is the
difficulty in visualization of the superior and posterior part of the distal
clavicle from the midlateral portal, causing an incomplete resection of the
distal clavicle. This could potentially lead to unresolved pain and therefore
surgical failure. We propose a technique for arthroscopic resection of the distal
clavicle and the medial portion of the acromion, without any added portal:
bipolar AC joint resection. The term "bipolar" is used because both the acromion
and the clavicle are resected, without injuring the superior capsule.
PMID- 29349024
TI - The Crossing Internal Suture Augmentation Technique to Protect the All-Inside
Anterior Cruciate Ligament Reconstruction Graft.
AB - The crossing internal suture augmentation technique is an all-inside technique of
anterior cruciate ligament reconstruction with augmentation of the hamstring
tendon autograft with a braided ultrahigh-molecular-weight polyester-polyethylene
suture tape resting on the adjustable cortical buttons on both the femoral and
tibial sides. The internal suture augmentation acts as a backbone supporting and
protecting the graft until the process of healing and ligamentization of the
graft is completed. The ends of the suture tape are tied on the tibial button and
additionally fixed to the tibia with a knotless anchor as a backup fixation with
the knee in full extension. The technique has the advantages of being minimally
invasive with small incisions and allowing preservation of the bone stock through
the use of sockets. It also allows early return to activity thanks to the more
secure rehabilitation and prevents early failure and stretching of the graft.
PMID- 29349025
TI - Anterior Capsule Reconstruction for Irreparable Subscapularis Tears.
AB - A subscapularis complete tear presents its own challenges in management. The
glenohumeral biomechanics and force couple are reliant on a competent and
functioning subscapularis muscle. An irreparable subscapularis makes those same
challenges even more difficult to address. Traditionally, this problem has been
addressed with tendon transfers, including pectoralis major or latissimus dorsi.
These techniques can alter the ideal biomechanics of the shoulder and have high
rates or failure. Iliotibial autograft or tibialis anterior have also been
wrought with high failure rates. Recently, the superior capsular reconstruction
has been described for irreparable tears of the supraspinatus and infraspinatus.
Theoretically, this procedure can act as a check rein against subluxation, and
may serve to reconnect the force couples of the rotator cuff. Anterior escape may
represent a similar challenge when the irreparable rotator cuff tendon is the
subscapularis. To address this, we describe an open anterior capsule
reconstruction technique with an acellular dermal graft. We theorize that this
procedure may serve in a similar capacity to its superior capsular counterpart.
PMID- 29349026
TI - Arthroscopic Management of Posterior Instability due to "Floating" Posterior
Inferior Glenohumeral Ligament Lesions.
AB - The "floating" posterior inferior glenohumeral ligament (floating PIGHL) is an
uncommon cause of posterior shoulder instability. This pathologic lesion, defined
as detachment of both the origin of the PIGHL (posterior Bankart lesion) and
insertion of the of the PIGHL from its humeral head insertion site, often results
in significant and persistent shoulder instability symptoms. An effective
surgical technique for arthroscopic repair of a floating PIGHL lesion is
described and demonstrated.
PMID- 29349027
TI - Arthroscopic Repair of Massive Subscapularis and Supraspinatus Tear by Double-Row
Knotless Technique.
AB - Subscapularis is the most powerful muscle in the rotator cuff. A steep learning
curve and constrained space anteriorly make the repair difficult. In massive
tears of the rotator cuff, repair of the subscapularis initially makes the
massive supraspinatus tear repairable. We present our technique to repair
subscapularis and supraspinatus tear by double-row anchors in a knotless and
tension-free manner. This technique can be done in partial or full-thickness
tears of the upper subscapularis.
PMID- 29349028
TI - Knotless Suture Bridge Technique in High-Grade Bursal-Sided Rotator Cuff Tears.
Is This The Way Forward?
AB - We present our technique in managing high-grade bursal-sided rotator cuff tears.
In this technique, the remaining intact cuff tissue is not sacrificed. The suture
bridge technique is used to uniformly tension the torn tissue to the rotator cuff
footprint. No knots are tied on the rotator cuff to minimize the tension on the
cuff. The sutures are then anchored on the lateral cortex of the humerus. This
technique allows repair with minimum tension while preserving the original length
of the rotator cuff.
PMID- 29349029
TI - Puncture Capsulotomy During Hip Arthroscopy for Femoroacetabular Impingement:
Preserving Anatomy and Biomechanics.
AB - We describe an arthroscopic technique for the treatment of labral pathology and
femoroacetabular impingement that provides excellent access to the central and
peripheral compartments while preserving the biomechanically crucial components
of hip joint stability. The hip capsule and the ligaments within it have been
shown to be integral to hip biomechanical stability. Other popular techniques
such as interportal and T-capsulotomy inherently damage the capsuloligamentous
complex of the hip and can be associated with postoperative gross instability,
micro-instability, heterotopic ossification, and seroma. Capsular closure may
mitigate some of these effects but has been associated with capsular
insufficiency and requires postoperative restrictions that can be prolonged. Our
surgical technique focuses on careful portal placement, replacement when
necessary, use of a switching stick to maximize peripheral compartment
visualization, and joint access in the most minimally invasive manner while
avoiding complications associated with extended capsulotomy. The objective of
this Technical Note is to describe a technique by which full access to the joint
can be obtained while not disrupting the biomechanics of the joint capsule.
PMID- 29349030
TI - Augmentation of Patellar Tendon Repair With Autologous Semitendinosus Graft-Porto
Technique.
AB - Patellar tendon ruptures can lead to significant functional deficiency of the
extensor mechanism of the knee. These injuries, because of their inherent nature
and associated complications, may require a complex treatment and remains a
challenge for orthopaedic surgeons. Current surgical techniques present
significant complications, including patellar fracture, damage to patellar
articular cartilage, and abnormal patella height. This note describes a surgical
technique to provide an additional reinforcement to the patellar tendon repair
with a semitendinous autograft, without the necessity to perform any transosseous
tunnels at the patella bone. First, the patellar tendon is repaired with an end
to-end technique and the semitendinous tendon is harvested. A transosseous tunnel
at the tibial tubercle is drilled and 2 rents are made, both medial and lateral
to the retinaculum at the level of the intermedial segment of the patella close
to the patellar margin. The graft is passed through the tunnel and rents in a U
shaped form. The graft is sutured along the length of the patellar tendon on both
margins in tension at 30 degrees of knee flexion. Fluoroscopy imaging is
performed to assess the patella height. This technique provides a significant
augmentation of patellar tendon, avoiding the potential patella bone tunnel
complications.
PMID- 29349031
TI - Modified Elmslie-Trillat Procedure for Distal Realignment of Patella Tendon.
AB - Patellofemoral dysfunction, due to either a patellofemoral malalignment or
patellar instability, is a complex and debilitating condition that significantly
decreases the knee function. Conservative management may yield significant
clinical outcomes; however, when morphologic anomalies are identified, the
surgical approach should be employed. Hence, several surgical procedures have
been described in the scientific literature aiming the correction of underlying
extensor mechanism malalignments. Still, the rate of complications is higher than
desirable. The described technique is based on the principles of transferring the
tibial tubercle medially as described in the Elmslie-Trillat technique. However,
a curvilinear horizontal cut is made prior to the vertical cut, which raises a
thick osseous fragment and allows the formation of a gutter when the osseous
fragment is moved medially. Whereas the horizontal gutter provides stability to
the bone fragment, the thicker dimension of the osseous fragment and retention of
the distal attachment significantly enhances the osteotomy union. Hence, adequate
pain relief and stability with very low postoperative morbidity could be
achieved. The purpose of this surgical note is to describe a modification to the
Elmslie-Trillat technique to treat patellofemoral dysfunctions, achieving a
higher osseous stability and decreased postoperative morbidity.
PMID- 29349032
TI - Revision Acromioclavicular-Coracoclavicular Reconstruction: Use of Precontoured
Button and 2 Allografts.
AB - Injuries to the acromioclavicular (AC) joint are common, particularly in the
young and active population. Approximately 9% of all shoulder girdle injuries
involve the AC joint, and AC joint dislocations represent approximately 8% of all
joint dislocations throughout the body. AC joint injuries are graded as type I
through type VI according to the Rockwood classification. Type I and II injuries
are typically treated nonoperatively, whereas type IV, V, and VI injuries are
most often treated surgically. A variety of surgical techniques have been
described, including anatomic and nonanatomic reconstruction. However, up to 80%
of patients go on to lose radiographic reduction, and between 20% and 30% have
complications leading to reoperation. Therefore, the objective of this Technical
Note is to describe our preferred technique for the treatment of AC joint
instability in the revision setting. This technique uses a Dog Bone Button
(Arthrex, Naples, FL) and 2 allografts.
PMID- 29349033
TI - Arthroscopic Reduction and Fixation of Tibial Spine Avulsion Fractures by a
Stainless Steel Wiring Technique.
AB - Several techniques of arthroscopic treatment of tibial spine avulsion fractures
have been described in the literature. These techniques include the use of
various fixation devices such as screws, K-wires, wiring, sutures, and suture
anchors. In this study, we evaluate a new wiring technique for the treatment of
these injuries. This technique involves fixation by stainless steel tension wires
passed over the fractured spine and tied over a bone bridge. The advantages of
this technique are that it aids in reduction, allows for compression of the
tibial spine fragment anatomically in its fracture bed, provides stable fixation
in difficult comminuted fractures, and allows for early mobilization and weight
bearing because of the solid fixation.
PMID- 29349034
TI - Arthroscopic Microfracture of Hip Chondral Lesions.
AB - Microfracture of hip chondral lesions has been performed for more than a decade
with modified treatment principles and techniques from knee arthroscopy. This
note and accompanying video review the pertinent techniques, pearls, and pitfalls
of the microfracture procedure in the treatment of hip chondral lesions. After
debridement of damaged chondral tissue, the size of the lesion is approximated to
determine the number of microfracture holes to create. The working portal may be
adjusted based on the site of the lesion. Microfracture picks of different angles
are used to ensure perpendicular advancement to a depth of 3 to 4 mm in the
subchondral bone. The holes are placed at a gap of approximately 3 to 4 mm. The
debris is washed out to obtain open holes connecting the marrow with the
articular surface. The microfracture procedure should be performed near the end
of the overall procedure to secure the bleeding bone marrow within the joint and
prevent washout.
PMID- 29349035
TI - Successful treatment of a patient with chyluria due to lymphangioleiomyomatosis
using sirolimus.
AB - Lymphangioleiomyomatosis (LAM) is a rare and progressive neoplastic disease of
young woman, characterized by the proliferation of abnormal smooth muscle-like
cells (LAM cells) in the lungs and axial lymphatics. A 44-year-old woman was
referred to our hospital because pleural effusion was detected during a health
checkup. She had chylothorax, chylous ascites, and chyluria, and her computed
tomography scan showed a solid tumor in the pelvis. Surgical biopsy was
performed; she was diagnosed as having LAM. We could not control the fluid
collection and chyluria using standard medical treatments. Therefore, we chose to
administer sirolimus, and her symptoms dramatically improved. The mechanism of
chyluria presumably involved LAM cell infiltrates in the ureter via the lymphatic
vessel flow, which causes LAM to develop because of ureter wall exposure.
PMID- 29349036
TI - Alternative topical anesthesia for bronchoscopy in a case of severe lidocaine
allergy.
AB - Lidocaine allergy presents a unique difficulty for both patients and providers
who undergo/perform bronchoscopy. We present a case of a 73 yo male with severe
lidocaine allergy who successfully underwent bronchoscopy with chloroprocaine
topical anesthesia and discuss alternative topical anesthetic agents that may be
used in this special situation.
PMID- 29349037
TI - Family history of alcoholism and the human brain response to oral sucrose.
AB - A heightened hedonic response to sweet tastes has been associated with increased
alcohol preference and alcohol consumption in both humans and animals. The
principal goal of this study was to examine blood oxygenation level dependent
(BOLD) activation to high- and low-concentration sweet solutions in subjects who
are either positive (FHP) or negative (FHN) for a family history of alcoholism.
Seventy-four non-treatment seeking, community-recruited, healthy volunteers (22.8
+/- 1.6 SD years; 43% men) rated a range of sucrose concentrations in a taste
test and underwent functional magnetic resonance imaging (fMRI) during oral
delivery of water, 0.83 M, and 0.10 M sucrose. Sucrose compared to water produced
robust activation in primary gustatory cortex, ventral insula, amygdala, and
ventral striatum. FHP subjects displayed greater bilateral amygdala activation
than FHN subjects in the low sucrose concentration (0.10 M). In secondary
analyses, the right amygdala response to the 0.10 M sucrose was greatest in FHP
women. When accounting for group differences in drinks per week, the family
history groups remained significantly different in their right amygdala response
to 0.10 M sucrose. Our findings suggest that the brain response to oral sucrose
differs with a family history of alcoholism, and that this response to a mildly
reinforcing primary reward might be an endophenotypic marker of alcoholism risk.
PMID- 29349039
TI - Engineering Escherichia coli for the production of terpene mixture enriched in
caryophyllene and caryophyllene alcohol as potential aviation fuel compounds.
AB - Recent studies have revealed that caryophyllene and its stereoisomers not only
exhibit multiple biological activities but also have desired properties as
renewable candidates for ground transportation and jet fuel applications. This
study presents the first significant production of caryophyllene and caryolan-1
ol by an engineered E. coli with heterologous expression of mevalonate pathway
genes with a caryophyllene synthase and a caryolan-1-ol synthase. By optimizing
metabolic flux and fermentation parameters, the engineered strains yielded 449
mg/L of total terpene, including 406 mg/L sesquiterpene with 100 mg/L
caryophyllene and 10 mg/L caryolan-1-ol. Furthermore, a marine microalgae
hydrolysate was used as the sole carbon source for the production of
caryophyllene and other terpene compounds. Under the optimal fermentation
conditions, 360 mg/L of total terpene, 322 mg/L of sesquiterpene, and 75 mg/L
caryophyllene were obtained from the pretreated algae hydrolysates. The highest
yields achieved on the biomass basis were 48 mg total terpene/g algae and 10 mg
caryophyllene/g algae and the caryophyllene yield is approximately ten times
higher than that from plant tissues by solvent extraction. The study provides a
sustainable alternative for production of caryophyllene and its alcohol from
microalgae biomass as potential candidates for next generation aviation fuels.
PMID- 29349038
TI - Abnormal neural hierarchy in processing of verbal information in patients with
schizophrenia.
AB - Previous research indicates abnormal comprehension of verbal information in
patients with schizophrenia. Yet the neural mechanism underlying the breakdown of
verbal information processing in schizophrenia is poorly understood. Imaging
studies in healthy populations have shown a network of brain areas involved in
hierarchical processing of verbal information over time. Here, we identified
critical aspects of this hierarchy, examining patients with schizophrenia. Using
functional magnetic resonance imaging, we examined various levels of information
comprehension elicited by naturally presented verbal stimuli; from a set of
randomly shuffled words to an intact story. Specifically, patients with first
episode schizophrenia (N = 15), their non-manifesting siblings (N = 14) and
healthy controls (N = 15) listened to a narrated story and randomly scrambled
versions of it. To quantify the degree of dissimilarity between the groups, we
adopted an inter-subject correlation (inter-SC) approach, which estimates
differences in synchronization of neural responses within and between groups. The
temporal topography found in healthy and siblings groups were consistent with our
previous findings - high synchronization in responses from early sensory toward
high order perceptual and cognitive areas. In patients with schizophrenia,
stimuli with short and intermediate temporal scales evoked a typical pattern of
reliable responses, whereas story condition (long temporal scale) revealed robust
and widespread disruption of the inter-SCs. In addition, the more similar the
neural activity of patients with schizophrenia was to the average response in the
healthy group, the less severe the positive symptoms of the patients. Our
findings suggest that system-level neural indication of abnormal verbal
information processing in schizophrenia reflects disease manifestations.
PMID- 29349040
TI - An unusual case of primary melioidotic prostatic abscess complicated by perianal
abscess.
AB - Burkholderia pseudomallei is recognized to cause severe and fatal infections.
Most of the infections caused by this facultative intracellular gram-negative
bacterium are pneumonia, soft tissue, genito-urinary and central nervous system
infection. We report an unusual case of primary prostatic abscess complicated by
perianal abscess caused by Burkholderia pseudomallei. Melioidosis related
anorectal infections have not been previously reported in the literature.
PMID- 29349041
TI - Unusual cause of severe diabetic ketoacidosis precipitated by Streptococcus
bovis/equinus (SBSEC) bacteremia: Case report and review of literature.
AB - Diabetic ketoacidosis is a feared complication in patients with diabetes mellitus
and poses high risk of mortality and morbidity unless treated in timely manner.
Infection is one of the most common precipitating factors for the development of
diabetic ketoacidosis. Bacteremia with Group A and Group B beta hemolytic
streptococcal strains are well known, however nonenterococcal Group D strains
such as the Streptococcus bovis/Streptococcus equinus complex (SBSEC) still
remains an understudied entity. Here we present a case of a 35-year-old Type I
diabetic female presenting with severe diabetic ketoacidosis with overlapping
features of hyperosmolar hyperglycemia, precipitated by Streptococcus
alactolyticus bacteremia, successfully treated with four-week course of
parenteral ceftriaxone. This case report emphasizes the potential importance of
SBSEC as an emerging pathologic strain and culprit for triggering diabetic
ketoacidosis which requires prompt diagnosis and targeted therapy.
PMID- 29349042
TI - An optimized targeted Next-Generation Sequencing approach for sensitive detection
of single nucleotide variants.
AB - Monitoring of minimal residual disease (MRD) has become an important clinical
aspect for early relapse detection during follow-up care after cancer treatment.
Still, the sensitive detection of single base pair point mutations via Next
Generation Sequencing (NGS) is hampered mainly due to high substitution error
rates. We evaluated the use of NGS for the detection of low-level variants on an
Ion Torrent PGM system. As a model case we used the c.1849G > T (p.Val617Phe)
mutation of the JAK2-gene. Several reaction parameters (e.g. choice of DNA
polymerase) were evaluated and a comprehensive analysis of substitution errors
was performed. Using optimized conditions, we reliably detected JAK2 c.1849G > T
VAFs in the range of 0.01-0.0015% which, in combination with results obtained
from clinical data, validated the feasibility of NGS-based MRD detection.
Particularly, PCR-induced transitions (mainly G > A and C > T) were the major
source of error, which could be significantly reduced by the application of
proofreading enzymes. The integration of NGS results for several common point
mutations in various oncogenes (i.e. IDH1 and 2, c-KIT, DNMT3A, NRAS, KRAS, BRAF)
revealed that the prevalent transition vs. transversion bias (3.57:1) has an
impact on site-specific detection limits of low-level mutations. These results
may help to select suitable markers for MRD detection and to identify individual
cut-offs for detection and quantification.
PMID- 29349043
TI - Vermicomposting and anaerobic digestion - viable alternative options for
terrestrial weed management - A review.
AB - The management of terrestrial weed is of great concern for the scientific
community as these weeds cause adverse effect in different ecosystems like
forest, agriculture and urban. The widespread of these weeds by their adaptive
capability and morphological advancement is difficult to control. Parthenium
hysterophorous, Lantana camara, Saccharum spontaneum, Ageratum conyzoides are the
weeds that spread all over the world. There are various management practices
employed for the control of this weeds. But all of these practices have some
drawbacks those are neither environment friendly nor economical. In this paper a
review has been done to evaluate various alternative management practices for
these terrestrial weeds and to analyze their feasibility. Vermicomposting and
anaerobic digestion can be viable alternative option which is cost effective as
well. There are few studies regarding vermicomposting and anaerobic digestions of
terrestrial weeds are done.
PMID- 29349044
TI - Evaluating the effect of enzymatic pretreatment on the anaerobic digestibility of
pulp and paper biosludge.
AB - Anaerobic digestion of biosludge has not yet been implemented in pulp mills due
to low biogas yields. Enzymatic pretreatment of biosludge has shown improvements
in biogas yields but results are varied. A key limitation of previous studies is
that they fail to consider the COD contribution from the enzyme solutions. The
aim of this study was to systematically investigate the potential for enzymatic
pretreatment on the anaerobic digestibility of pulp mill biosludge. Out of the
six enzymes tested, four enhanced the anaerobic digestibility of biosludge. At
the end of the BMP, a maximum improvement of 26% in biogas yield was observed
with protease from B. licheniformis. There was no correlation between enzymatic
activities on standard substrates and/or on biosludge and the effect of enzymes
on biogas yields. Enzymes have potential for improving biosludge anaerobic
digestibility but more research on optimal conditions and potential synergies
with other pretreatment is needed.
PMID- 29349045
TI - Advantages, Disadvantages, Indications, Contraindications and Surgical Technique
of Laryngeal Airway Mask.
AB - The beauty of the laryngeal mask is that it forms an air tight seal enclosing the
larynx rather than plugging the pharynx, and avoid airway obstruction in the
oropharynx. The goal of its development was to create an intermediate form of
airway management face mask and endotracheal tube. Indication for its use
includes any procedure that would normally involve the use of a face mask. The
laryngeal mask airway was designed as a new concept in airway management and has
been gaining a firm position in anesthetic practice. Despite wide spread use the
definitive role of the laryngeal mask airway is yet to be established. In some
situations, such as after failed tracheal intubation or in oral surgery its use
is controversial. There are several unresolved issues, for example the effect of
the laryngeal mask on regurgitation and whether or not cricoids pressure prevents
placement of mask. We review the techniques of insertion, details of
misplacement, and complications associated with use of the laryngeal mask. We
then attempt to clarify the role of laryngeal mask in air way management during
anesthesia, discussing the advantages and disadvantages as well as indications
and contraindications of its use in oral and maxillofacial surgery.
PMID- 29349046
TI - Reduction of Closed Frontal Sinus Fractures through Suprabrow Approach.
AB - Background: The traditional approach for reduction of frontal sinus fractures is
coronal incision. Inherent complications of the coronal approach include long
scar, hair loss, and long operation time. We describe a simple approach for the
reduction of frontal sinus anterior wall fractures using a suprabrow incision
that is commonly used for brow lift. Methods: From March 2007 to October 2016,
the authors identified patients with anterior wall frontal sinus fractures
treated by open reduction through a suprabrow incision. Only cases with
photographic/radiographic documentation and a minimum follow-up of 6 months were
included. The incision line was designed to be at the upper margin of the
eyebrow. Medical records and radiographic data were retrospectively reviewed.
Surgical outcomes, cosmetic results, and complication were assessed. The patient
scale of the patient and observer scar assessment scale was used to assess
patient satisfaction for incisional scar at the 6-month follow-up. Results:
Thirty-one patients underwent fracture reduction through a suprabrow approach
during the study period, with a mean follow-up of 41 months. No patients showed
any recurrent displacement, eyebrow asymmetry, or infection during follow-up.
Thirteen patients reported their forehead paresthesia postoperatively, and 12 of
them had preoperative symptom. One patient complained of incisional scar and
underwent scar revision. All patients were satisfied with their eyebrow and
forehead contour. Conclusion: The suprabrow approach allowed for an accurate
reduction of the fractures in the anterior wall frontal sinus by providing direct
visualization of the fracture. This transcutaneous approach can effectively
restore forehead contour with acceptable postoperative complications and patient
satisfaction.
PMID- 29349047
TI - Reduction of the Isolated Anterior Wall of the Maxillary Sinus Fracture with
Double Urinary Balloon Catheters and Fibrin Glue.
AB - Background: Conservative treatment is performed for isolated anterior wall of the
maxillary sinus fractures, in many cases when the fracture is clinically not
severe and asymptomatic. Despite the absence of symptoms, complications such as
sinusitis, rhinitis, and chronic purulent secretion may develop; therefore,
successful reduction is required. We attempted to reduce the risk of
complications using an alternative technique: reduction of the fracture with two
urinary balloon catheters inserted through the maxillary ostium and fixation
using fibrin glue, which minimizes the damage to the bony fragments and sinus
mucosa. Methods: In this study, 38 patients who were diagnosed with an isolated
anterior wall of the maxillary sinus fracture at our hospital between January
2014 and January 2017 were enrolled. The fracture site was exposed via the
Caldwell-Luc approach followed by reduction through the insertion of two urinary
balloon catheters using a nasal endoscope and fixation with fibrin glue. The sex,
cause of fracture, physical examination, and presence of complications were
examined and patient's medical records and facial bone computed tomography scans
were analyzed. Results: Radiological evaluation showed that there was no evidence
of collapsed reduction fragments. Although some patients had remaining symptoms
of hypoesthesia (15%; 3 patients), there were no complications such as infection,
rhinitis, sinusitis, and chronic purulent secretion at the surgical site.
Conclusion: In this study, we present an alternative surgical technique using two
urinary balloon catheters and fibrin glue for the successful reconstruction of an
isolated anterior wall of the maxillary sinus fracture. This technique enables
precise restoration with a reduced risk of complications.
PMID- 29349048
TI - Versatility of Modified Nasolabial Flap in Oral and Maxillofacial Surgery.
AB - Background: To evaluate the versatility and reach of modified nasolabial flap
used in reconstruction of defects created in and around the oral cavity. Methods:
A total number of 20 cases were selected. Out of which 13 were males and 7
females. The age of these patients ranged from 24-63 years. 29 modified
nasolabial flaps were raised in twenty patients. Based on clinical and
histopathological examination, out of 20 patients, 14 patients were diagnosed
with oral submucous fibrosis, 3 with verrucous carcinoma, 1 with squamous
papilloma, 1 with oro-antral fistula and 1 with traumatic loss of lower lip.
Results: Minimum preoperative interincisal distance (IID) was 0 mm and maximum
was 15 mm with mean of 6.00+/-4.76 mm in patients with oral submucous fibrosis
and 12 months postoperatively minimum IID was 16 mm and maximum was 41 mm with
mean of 28.00+/-8.96 mm. In one case, dehiscence (3.4%) was noted on the anterior
tip for which tip revision was done. Bulky appearance of the flap intraorally was
observed in 2 cases (6.9%). Five (17.2%) among the 29 flaps had visible scar at
the donor site postoperatively up to 3 months. Conclusion: Numerous
reconstructive techniques have been employed in the reconstruction of small to
intermediate sized defects of oral cavity. Modified nasolabial flap is a
versatile flap which has robust vascularity and can be successfully used with
minimal complications. It can be rotated intraorally to extend from the soft
palate to the lip. Thus, it can be used efficiently to treat the small defects of
the oral cavity as well as recreating lost lip structure.
PMID- 29349049
TI - The Reliability of the Transconjunctival Approach for Orbital Exposure:
Measurement of Positional Changes in the Lower Eyelid.
AB - Background: Lower eyelid incisions are widely used for the orbital approach in
periorbital trauma and aesthetic surgery. In general, the subciliary approach is
known to cause disposition of the lower eyelid by scarring the anterior lamella
in some cases. On the other hand, many surgeons believe that a transconjunctival
approach usually does not result in such complications and is a reliable method.
We measured positional changes in the lower eyelid in blowout fracture repair
since entropion is one of the most serious complications of the transconjunctival
orbital approach. Methods: To measure the positional changes in the lower
eyelids, we analyzed preoperative and postoperative photographs over various time
intervals. In the analysis of the photographs, marginal reflex distance 2 (MRD2)
and eyelash angle were used as an index of eyelid position. Statistical analyses
were performed to identify the significance in the positional changes. All
patients underwent orbital reconstruction through a transconjunctival incision by
a single plastic surgeon. Results: In 42 blowout fracture patients, there was no
statistical significant difference in the MRD2 and eyelash angle. Furthermore,
there were no clinical complications, such as infection, hematoma, bleeding, or
implant protrusion, during the follow-up periods. Conclusion: The advantages of
the transconjunctival approach for orbital access include minimal scarring and a
lower risk of eyelid displacement compared with other approaches. Based on these
results, we recommend the transconjunctival approach for orbital exposure as a
safe and reliable method.
PMID- 29349050
TI - A Comparison of the Local Flap and Skin Graft by Location of Face in
Reconstruction after Resection of Facial Skin Cancer.
AB - Background: Surgery for reconstruction of defects after surgery should be
performed selectively and the many points must be considered. The authors
conducted this study to compare the local flap and skin graft by facial location
in the reconstruction after resection of facial skin cancer. Methods: The authors
performed the study in patients that had received treatment in Department of
Plastic Surgery, Gyeongsang National University. The cases were analyzed
according to the reconstruction methods for the defects after surgery, sex, age,
tumor site, and tumor size. Additionally, the authors compared differences of
aesthetic satisfaction (out of 5 points) of patients in the local flap and skin
graft by facial location after resection of facial skin cancer by dividing the
face into eight areas. Results: A total of 153 cases were confirmed. The most
common facial skin cancer was basal cell carcinoma (56.8%, 87 cases), followed by
squamous cell carcinoma (37.2%, 57 cases) and bowen's disease (5.8%, 9 cases).
The most common reconstruction method was local flap 119 cases (77.7%), followed
by skin graft 34 cases (22.3%). 86 patients answered the questionnaire and mean
satisfaction of the local flap and skin graft were 4.3 and 3.5 (p=0.04),
respectively, indicating that satisfaction of local flap was significantly high.
Conclusion: When comparing satisfaction of patients according to results, local
flap shows excellent effects in functional and cosmetic aspects would be able to
provide excellent results rather than using a skin graft with poor touch and tone
compared to the surrounding normal skin.
PMID- 29349051
TI - Anisakiasis Involving the Oral Mucosa.
AB - Anisakis is a parasite with life cycles involving fish and marine mammals. Human
infection, anisakiasis, occurs with the ingestion of raw infected seafood and
usually presents with acute or chronic gastrointestinal symptoms from esophageal
or gastric invasion. We report a rare caseinvolving the oral cavity. A 39-year
old male presented with oral and sub-sternal pain of one day duration after
eating raw cuttlefish. Physical examination revealed areas of erythema and edema
with a central white foreign particle on the labial and buccal mucosa. With
microscopic field we could remove the foreign material from the lesions. The
foreign material was confirmed to be Anisakis. Anisakis was also removed from the
esophagus by esophagogastroduodenoscopy. The patient was discharged the following
day without complication. Anisakiasis is frequently reported in Korea and Japan,
countries where raw seafood ingestion is popular. The symptoms of acute
anisakiasis include pain, nausea, and vomiting and usually begin 2-12 hours after
ingestion. The differential diagnosis includes food poisoning, acute gastritis,
and acute pancreatitis. A history of raw seafood ingestion is important to the
diagnosis of anisakiasis. Treatment is complete removal of the Anisakis to
relieve acute symptoms and prevent chronic granulomatous inflammation.
PMID- 29349052
TI - Malar Relocation with Reverse-L Osteotomy and Autogenous Bone Graft.
AB - The zygomaticomaxillary complex (ZMC) functions as a buttress for the face and is
the cornerstone to a person's aesthetic appearance, by both setting the midfacial
width and providing prominence to the cheek. Malar deficiency is often acquired
by blunt injury incurred in a traumatic accident, resulting in ZMC fracture. A 48
year-old male patient presented a right ZMC fracture after contusion injury by a
baseball. He only received conservative management and later he suffered
discomfort during mouth opening at the moment of mastication, due to trismus
involving the temporomandibular joint. In the current case, we describe a
surgical technique, by which the malar body is shifted anteriorly and laterally
after combined oblique-vertical osteotomy. The technique presented, eventually
restored the former aesthetic position of the malar complex and symmetry, and,
moreover, improved mastication function.
PMID- 29349053
TI - Myxoid Solitary Fibrous Tumor on the Scalp.
AB - Myxoid solitary fibrous tumor (SFT) is very rare soft tissue neoplasm. It is
microscopically composed of spindle cells which is individually separated by
delicate band of collagen fibers. And this tumor cells are immunohisto
chemistrically highlighted by CD34. Myxoid SFT has indolent clinical course and a
good prognosis, so it is important to make a diagnosis because of its
morphological similarities to myxoid spindle cell neoplasms that have different
prognoses and treatment. We report the case of a 20-year-old female with a myxoid
SFT found in the left temporo-parietal scalp. This case report appears to be the
first reported scalp occurrence of this rare tumor.
PMID- 29349054
TI - Post-Traumatic Peripheral Giant Osteoma in the Frontal Bone.
AB - Osteomas are benign, slow-growing tumors that most frequently occur in the
craniomaxillofacial region. These tumors are mostly asymptomatic and are
generally found incidentally. A giant osteoma is generally considered to be
greater than 30 mm in diameter or 110 g in weight. A 35-year-old female presented
to us with complaints of a firm mass that showed continuous growth on the
forehead following trauma. A hairline incision was made to expose the osteoma.
Biopsy of the tumor confirmed a osteoma. There were no complications after
surgery. Postoperative computed tomography revealed that the tumor was completely
removed. Because a peripheral giant osteoma of the frontal bone with a history of
trauma is a rare finding, thorough history-taking, physical examination, and
preoperative imaging tests are needed for patients with a history of trauma to
rule out a giant osteoma.
PMID- 29349055
TI - Reconstruction of a Traumatic Cleft Earlobe Using a Combination of the Inverted V
Shaped Excision Technique and Vertical Mattress Suture Method.
AB - Traumatic cleft earlobes are a common problem encountered by plastic and
reconstructive surgeons. Various techniques have been reported for the repair of
traumatic cleft earlobes. Usually, the techniques of split earlobe repair are
divided into two categories, namely straight- and broken-line repairs. Straight
line repair is simple and easy, but scar contracture frequently results in
notching of the inferior border of the lobule. It can be avoided by the broken
line repair such as Z-plasty, L-plasty, or a V-shaped flap. Between April 2016
and February 2017, six patients who presented with traumatic cleft earlobe
underwent surgical correction using a combination of the inverted V-shaped
excision technique and vertical mattress suture method. All the patients were
female and had a unilateral complete cleft earlobe. No postoperative notching of
the inferior border the lobule occurred during 6-16 months of follow-up. Without
the use of a broken-line repair, both the patients and the operators attained
aesthetically satisfactory results. Therefore, the combination of the inverted V
shaped excision technique and vertical mattress suture method is considered
useful in the treatment of traumatic cleft earlobes.
PMID- 29349056
TI - Sinus Tract Formation with Chronic Inflammatory Cystic Mass after Beta Tricalcium
Phosphate Insertion.
AB - Beta tricalcium phosphate (beta-TCP) is one of allogenic bone substitute which is
known to have interconnected pores that draws cell and nutrients for bone
generation. It has been resulted in good outcomes for bone defect coverage or
augmentation. However, several studies have also reported negative outcomes and
associated complications including unexpected formation of cystic mass,
continuous pain and secretion. We present the case of a 36-year-old man with a
right cheek cystic mass who had a history of right zygomaticomaxillary (ZM)
complex fracture and surgical correction with beta-TCP powder insertion to ZM
bone defect. Excisional biopsy under local anesthesia revealed calcified mass in
a sinus tract which was found to be connected to the ZM bone defect site in
postoperative computed tomography image. Further excision under general
anesthesia was performed to remove the sinus tract and fine granules which filled
the original defect site. Pathologic report revealed bony spicules and
calcification materials with chronic foreign body reaction. Postoperative
complications and recurrence were not reported.
PMID- 29349057
TI - Ectopic Preauricular Sinus in a Facial Cleft and Microtia Patient.
AB - Preauricular sinus is a congenital malformation that is very commonly encountered
among the general population and it has especially high prevalence among Asians
when compared to other ethnic groups. It can often go unnoticed or easily
overlooked by the patient or even by doctors because most of them are
asymptomatic and is most of the time only a tiny pit that can be trivial in terms
of aesthetics. We report a very rare and unique case that has no precedence what
so ever; hence no reported case in the literature: an ectopic preauricular sinus
in a facial cleft and microsomia patient.
PMID- 29349058
TI - Rhabdomyomatous Mesenchymal Hamartoma Presenting as a Midline Mass on a Chin.
AB - A 17-month-old boy was evaluated for a midline mass on his chin. The mass was
anchored to the mentalis muscle with a stalk-like structure. The pathological
diagnosis of the mass was rhabdomyomatous mesenchymal hamartoma. This is the
first report of rhabdomyomatous mesenchymal hamartoma presenting as a midline
chin mass in Korean pediatric patients.
PMID- 29349059
TI - Dear Members of the Association.
PMID- 29349060
TI - Sost Deficiency does not Alter Bone's Lacunar or Vascular Porosity in Mice.
AB - SCLEROSTIN (Sost) is expressed predominantly in osteocytes acting as a negative
regulator of bone formation. In humans, mutations in the SOST gene lead to
skeletal overgrowth and increased bone mineral density, suggesting that
SCLEROSTIN is a key regulator of bone mass. The function of SCLEROSTIN as an
inhibitor of bone formation is further supported by Sost knockout (KO) mice which
display a high bone mass with elevated bone formation. Previous studies have
indicated that Sost exerts its effect on bone formation through Wnt-mediated
regulation of osteoblast differentiation, proliferation, and activity. Recent in
vitro studies have also suggested that SCLEROSTIN regulates angiogenesis and
osteoblast-to-osteocyte transition. Despite this wealth of knowledge of the
mechanisms responsible for SCLEROSTIN action, no previous studies have examined
whether SCLEROSTIN regulates osteocyte and vascular configuration in cortices of
mouse tibia. Herein, we image tibiae from Sost KO mice and their wild-type (WT)
counterparts with high-resolution CT to examine whether lack of SCLEROSTIN
influences the morphometric properties of lacunae and vascular canal porosity
relating to osteocytes and vessels within cortical bone. Male Sost KO and WT mice
(n = 6/group) were sacrificed at 12 weeks of age. Fixed tibiae were analyzed
using microCT to examine cortical bone mass and architecture. Then, samples were
imaged by using benchtop and synchrotron nano-computed tomography at the
tibiofibular junction. Our data, consistent with previous studies show that, Sost
deficiency leads to significant enhancement of bone mass by cortical thickening
and bigger cross-sectional area and we find that this occurs without
modifications of tibial ellipticity, a measure of bone shape. In addition, our
data show that there are no significant differences in any lacunar or vascular
morphometric or geometric parameters between Sost KO mouse tibia and WT
counterparts. We, therefore, conclude that the significant increases in bone mass
induced by Sost deficiency are not accompanied by any significant modification in
the density, organization, or shape of osteocyte lacunae or vascular content
within the cortical bone. These data may imply that SCLEROSTIN does not modify
the frequency of osteocytogenic recruitment of osteoblasts to initiate terminal
osteocytic differentiation in mice.
PMID- 29349061
TI - Self-Reported Adverse Drug Reactions, Medication Adherence, and Clinical Outcomes
among Major Depressive Disorder Patients in Ethiopia: A Prospective Hospital
Based Study.
AB - Background: There is paucity of data on prevalence of Adverse Drug Reactions
(ADRs) and adherence and clinical outcomes of antidepressants. The present study
determined the magnitude of ADRs of antidepressants and their impact on the level
of adherence and clinical outcome. Methods: A prospective cross-sectional study
was conducted among depression patients from September 2016 to January 2017 at
Gondar University Hospital psychiatry clinic. The Naranjo ADR probability scale
was employed to assess the ADRs. The rate of medication adherence was determined
using Morisky Medication Adherence Measurement Scale-Eight. Results: Two hundred
seventeen patients participated in the study, more than half of them being males
(122; 56.2%). More than one-half of the subjects had low adherence to their
medications (124; 57.1%) and about 186 (85.7%) of the patients encountered ADR.
The most common ADR was weight gain (29; 13.2%). More than one-half (125; 57.6%)
of the respondents showed improved clinical outcome. Optimal level of medication
adherence decreased the likelihood of poor clinical outcome by 56.8%. Conclusion:
ADRs were more prevalent. However, adherence to medications was very poor in the
setup. Long duration of depression negatively affects the rate of adherence. In
addition, adherence was found to influence the clinical outcome of depression
patients.
PMID- 29349063
TI - Abdominal Manual Therapy Repairs Interstitial Cells of Cajal and Increases
Colonic c-Kit Expression When Treating Bowel Dysfunction after Spinal Cord
Injury.
AB - Background: This study aimed to evaluate the therapeutic effects of abdominal
manual therapy (AMT) on bowel dysfunction after spinal cord injury (SCI),
investigating interstitial cells of Cajal (ICCs) and related c-kit expression.
Methods: Model rats were divided as SCI and SCI with drug treatment (intragastric
mosapride), low-intensity (SCI + LMT; 50 g, 50 times/min), and high-intensity AMT
(SCI + HMT; 100 g, 150 times/min). After 14 days of treatment, weight, improved
Basso-Beattie-Bresnahan (BBB) locomotor score, and intestinal movement were
evaluated. Morphological structure of spinal cord and colon tissues were
examined. Immunostaining, RT-PCR, and western blot were used to assess c-kit
expression. Results: In SCI rats, AMT could not restore BBB, but it significantly
increased weight, shortened time to defecation, increased feces amounts, and
improved fecal pellet traits and colon histology. AMT improved the number,
distribution, and ultrastructure of colonic ICCs, increasing colonic c-kit mRNA
and protein levels. Compared with the SCI + Drug and SCI + LMT groups, the SCI +
HMT group showed better therapeutic effect in improving intestinal transmission
function and promoting c-kit expression. Conclusions: AMT is an effective therapy
for recovery of intestinal transmission function. It could repair ICCs and
increase c-kit expression in colon tissues after SCI, in a frequency-dependent
and pressure-dependent manner.
PMID- 29349062
TI - Circular RNAs: Biogenesis, Function, and a Role as Possible Cancer Biomarkers.
AB - Circular RNAs (circRNAs) are a class of noncoding RNAs (ncRNAs) that form
covalently closed continuous loop structures, lacking the terminal 5' and 3'
ends. CircRNAs are generated in the process of back-splicing and can originate
from different genomic regions. Their unique circular structure makes circRNAs
more stable than linear RNAs. In addition, they also display insensitivity to
ribonuclease activity. Generally, circRNAs function as microRNA (miRNA) sponges
and have a regulatory role in transcription and translation. They may be also
translated in a cap-independent manner in vivo, to generate specific proteins. In
the last decade, next-generation sequencing techniques, especially RNA-seq, have
revealed great abundance and also dysregulation of many circRNAs in various
diseases, suggesting their involvement in disease development and progression.
Regarding their high stability and relatively specific differential expression
patterns in tissues and extracellular environment (e.g., body fluids), they are
regarded as promising novel biomarkers in cancer. Therefore, we focus this review
on describing circRNA biogenesis, function, and involvement in human cancer
development and address the potential of circRNAs to be effectively used as novel
cancer diagnostic and prognostic biomarkers.
PMID- 29349064
TI - From Clinical Symptoms to MR Imaging: Diagnostic Steps in Adenomyosis.
AB - Adenomyosis or endometriosis genitalis interna is a frequent benign disease of
women in fertile age. It causes symptoms like bleeding disorders and dysmenorrhea
and seems to have a negative effect on fertility. Adenomyosis can be part of a
complex genital and extragenital endometriosis but also can be found as a
solitary uterine disease. While peritoneal endometriosis can be easily diagnosed
by laparoscopy with subsequent biopsy, the determination of adenomyosis is
difficult. In the following literature review, the diagnostic methods clinical
history and symptoms, gynecological examination, 2D and 3D transvaginal
ultrasound, MRI, hysteroscopy, and laparoscopy will be discussed step by step in
order to evaluate their predictive value in the diagnosis of adenomyosis.
PMID- 29349065
TI - Beneficial Effects of 6-Month Supplementation with Omega-3 Acids on Selected
Inflammatory Markers in Patients with Chronic Kidney Disease Stages 1-3.
AB - Introduction: Chronic kidney disease (CKD) is accompanied by inflammation. The
aim of this study was to evaluate the effect of 6-month supplementation with
omega-3 acids on selected markers of inflammation in patients with CKD stages 1
3. Methods: Six-month supplementation with omega-3 acids (2 g/day) was
administered to 87 CKD patients and to 27 healthy individuals. At baseline and
after follow-up, blood was taken for C-reactive protein (CRP) and monocyte
chemotactic protein-1 (MCP-1) concentration and white blood cell (WBC) count.
Serum concentration of omega-3 acids-eicosapentaenoic acid (EPA), docosahexaenoic
acid (DHA), and alpha-linolenic acid (ALA)-was determined using gas
chromatography. And 24-hour urinary collection was performed to measure MCP-1
excretion. Results: After six-month omega-3 supplementation, ALA concentration
increased in CKD patients and in the reference group, while EPA and DHA did not
change. At follow-up, a significant decrease in urinary MCP-1 excretion in CKD (p
= 0.0012) and in the reference group (p = 0.001) was found. CRP, serum MCP-1, and
WBC did not change significantly. The estimated glomerular filtration rate (eGFR)
did not change significantly in the CKD group. Conclusions: The reduction of
urinary MCP-1 excretion in the absence of MCP-1 serum concentration may suggest a
beneficial effect of omega-3 supplementation on tubular MCP-1 production. Trial
Registration: This study was registered in ClinicalTrials.gov (identifier:
NCT02147002).
PMID- 29349066
TI - Cadmium Exposure as a Putative Risk Factor for the Development of Pancreatic
Cancer: Three Different Lines of Evidence.
AB - Although profoundly studied, etiology of pancreatic cancer (PC) is still rather
scant. Exposure to cadmium (Cd), a ubiquitous metal associated with well
established toxic and carcinogenic properties, has been hypothesized to one
putative cause of PC. Hence, we analyzed recently published observational
studies, meta-analyses, and experimental animal and in vitro studies with the aim
of summarizing the evidence of Cd involvement in PC development and describing
the possible mechanisms. Consolidation of epidemiological data on PC and exposure
to Cd indicated a significant association with an elevated risk of PC among
general population exposed to Cd. Cadmium exposure of laboratory animals was
showed to cause PC supporting the findings suggested by human studies. The
concordance with human and animal studies is buttressed by in vitro studies,
although in vitro data interpretation is problematic. In most instances, only
significant effects are reported, and the concentrations of Cd are excessive,
which would skew interpretation. Previous reports suggest that oxidative stress,
apoptotic changes, and DNA cross-linking and hypermethylation are involved in Cd
mediated carcinogenesis. Undoubtedly, a significant amount of work is still
needed to achieve a better understanding of the Cd involvement in pancreatic
cancer which could facilitate prevention, diagnosis, and therapy of this fatal
disease.
PMID- 29349067
TI - Modulation of Immune Function in Rats Using Oligosaccharides Extracted from Palm
Kernel Cake.
AB - To investigate the prebiotic and immunomodulatory effects of PKC extract
(OligoPKC) a total of 24 male rats were randomly assigned to three treatment
groups receiving basal diet (control), basal diet containing 0.5% OligoPKC, or
basal diet containing 1% OligoPKC for four weeks. We found that OligoPKC had no
significant effect on the tested growth parameters. However, it increased the
size of the total and beneficial bacterial populations while reducing pathogen
populations. OligoPKC increased the concentration of immunoglobulins in the serum
and cecal contents of rats. It also enhanced the antioxidant capacity of the
liver while reducing lipid peroxidation in liver tissue. OligoPKC affected the
expression of genes involved in immune system function in the intestine.
Therefore, OligoPKC could be considered a potential mannan-based prebiotic for
humans and animals due to its beneficial effects on the health and well-being of
the model rats.
PMID- 29349068
TI - Restrictive Transfusion Strategy Does Not Affect Clinical Prognosis in Patients
with Ectopic Pregnancy.
AB - To assess the effects of restrictive transfusion strategy on hemoglobin (Hb)
levels and prognosis in patients with ectopic pregnancy and severe hemorrhage
undergoing emergency surgery, patient data were collected from 2012 to 2016.
Following transfusion guidelines, restrictive transfusion was performed; at Hb
levels of 60-70 to 100 g/L, transfusion was continued or not based on disease
status. The patients were divided into four groups: blood loss < 400 ml (N1), 400
799 ml (N2), 800-1199 ml (N3), and >=1200 ml (N4). Several prognosis parameters
were assessed. Group N4 was further divided based on blood loss amounts (1200
1999, 2000-2999, 3000-3999, and 4000-5000 ml) for subgroup analyses. Blood loss,
hemoglobin levels at discharge, and American Society of Anesthesiologists (ASA)
scores were not associated with patient prognostic parameters, including
intensive care unit (ICU) occupancy, cure, and healing rates, and surgical
complications and hospital stay. No statistically significant difference was
obtained in hospital stay among N1, N2, and N3 groups. Compared with N1 patients,
cases with blood loss >= 1200 ml had significantly longer hospital stay.
Interestingly, hospital stay was correlated with surgical approach, location of
pregnancy, and operation time. Restrictive transfusion strategy could be safely
used for emergency surgery in ectopic pregnancy with acute blood loss.
PMID- 29349069
TI - A Novel Methicillin-Resistant Staphylococcus aureus t11469 and a Poultry Endemic
Strain t002 (ST5) Are Present in Chicken in Ebonyi State, Nigeria.
AB - Background: The changing epidemiology of methicillin-resistant Staphylococcus
aureus (MRSA) from a hospital-associated pathogen to an organism commonly found
in the community and in livestock reflects an organism well-equipped to survive
in diverse environments and adjust to different environmental conditions
including antimicrobial use. Methods: We investigated the molecular epidemiology
of S. aureus and MRSA in poultry in Ebonyi State, Nigeria. Samples were collected
from 1800 birds on 9 different farms within the state. Positive isolates were
tested for antibiotic susceptibility and molecular typing. Results: Prevalence in
birds was 13.7% (247/1800). MRSA prevalence in poultry was 0.8%. The prevalence
of MRSA in broilers and layers was 1.2% and 0.4%, respectively. All tested
isolates were susceptible to vancomycin. Molecular analysis of the isolates
revealed 3 spa types: t002, t084, and a novel spa type, t11469. The novel spa
type t11469 belonged to sequence type ST5. Conclusion: The detection of t002 in
chicken suggests the presence of livestock-associated MRSA in poultry in Ebonyi
State. The detection of the new spa type t11469 in poultry that has not been
characterised to ascertain its pathogenic potential remains a cause for concern,
especially as some were found to carry PVL genes, a putative virulence factor in
staphylococcal infection.
PMID- 29349070
TI - EEG Recording and Online Signal Processing on Android: A Multiapp Framework for
Brain-Computer Interfaces on Smartphone.
AB - Objective: Our aim was the development and validation of a modular signal
processing and classification application enabling online electroencephalography
(EEG) signal processing on off-the-shelf mobile Android devices. The software
application SCALA (Signal ProCessing and CLassification on Android) supports a
standardized communication interface to exchange information with external
software and hardware. Approach: In order to implement a closed-loop brain
computer interface (BCI) on the smartphone, we used a multiapp framework, which
integrates applications for stimulus presentation, data acquisition, data
processing, classification, and delivery of feedback to the user. Main Results:
We have implemented the open source signal processing application SCALA. We
present timing test results supporting sufficient temporal precision of audio
events. We also validate SCALA with a well-established auditory selective
attention paradigm and report above chance level classification results for all
participants. Regarding the 24-channel EEG signal quality, evaluation results
confirm typical sound onset auditory evoked potentials as well as cognitive event
related potentials that differentiate between correct and incorrect task
performance feedback. Significance: We present a fully smartphone-operated,
modular closed-loop BCI system that can be combined with different EEG amplifiers
and can easily implement other paradigms.
PMID- 29349071
TI - Effect of Ultrasound-Enhanced Transdermal Drug Delivery Efficiency of
Nanoparticles and Brucine.
AB - Brucine is the active component in traditional Chinese medicine "Ma-Qian-Zi"
(Strychnos nux-vomica Linn), with capabilities of analgesic, anti-inflammatory,
anti-tumor and so on. It is crucial how to break through the impact of cuticle
skin which reduces the penetration of drugs to improve drug transmission rate.
The aim of this study is to improve the local drug concentration by using
ultrasound. We used fresh porcine skin to study the effects of ultrasound on the
transdermal absorption of brucine under the influence of various acoustic
parameters, including frequency, amplitude and irradiation time. The transdermal
conditions of yellow-green fluorescent nanoparticles and brucine in skin samples
were observed by laser confocal microscopy and ultraviolet spectrophotometry. The
results show that under ultrasonic conditions, the permeability of the skin to
the fluorescent label and brucine (e.g., the depth and concentration of
penetration) is increased compared to its passive diffusion permeability. The
best ultrasound penetration can make the penetration depth of more than 110
microns, fluorescent nanoparticles and brucine concentration increased to 2-3
times. This work will provide supportive data on how the brucine is better used
for transdermal drug delivery (TDD).
PMID- 29349072
TI - Complex Segregation Analysis Provides Evidence for Autosomal Dominant
Transmission in the Chinese Han Families with Ankylosing Spondylitis.
AB - Introduction: Familial aggregation of ankylosing spondylitis (AS) has been
frequently noticed. However, the mode of inheritance in AS remains poorly
understood. Our aim was to determine the mode of inheritance best fitting the
observed transmission pattern of AS families. Methods: Families with 5 or more AS
patients diagnosed with 1984 modified New York criteria were recruited. We
performed complex segregation analysis for a binary trait in regressive
multivariate logistic models. The inheritance models, including sporadic, major
gene, environmental, general, and other 9 models, were compared by likelihood
ratio tests and Akaike's Information Criterion. Results: This research included 9
Chinese Han AS families with a total number of 315 persons, including 74
patients. First, familial association was determined. Sporadic with familial
association model was rejected when compared with either the general model or the
homogeneous general model (p < 0.001). The environmental model was also rejected
when compared with general models (p < 0.02). Mendelian dominate mode fitted best
in 5 AS families, while Tau AB free model best explained the mode of inheritance
in these AS families. Conclusion: This study provided evidence in support of
Mendelian dominant mode and firstly discovered a non-Mendelian mode called tau AB
free inheritance mode in AS.
PMID- 29349073
TI - Anatomical Basis of the Myofascial Trigger Points of the Gluteus Maximus Muscle.
AB - Myofascial pain syndrome is characterized by pain and limited range of motion in
joints and caused by muscular contracture related to dysfunctional motor end
plates and myofascial trigger points (MTrPs). We aimed to observe the anatomical
correlation between the clinically described MTrPs and the entry point of the
branches of the inferior gluteal nerve into the gluteus maximus muscle. We
dissected twenty gluteus maximus muscles from 10 human adult cadavers (5 males
and 5 females). We measured the muscles and compiled the distribution of the
nerve branches into each of the quadrants of the muscle. Statistical analysis was
performed by using Student's t-test and Kruskal-Wallis tests. Although no
difference was observed either for muscle measurements or for distribution of
nerve branching among the subjects, the topography of MTrPs matched the
anatomical location of the entry points into the muscle. Thus, anatomical
substract of the MTrPs may be useful for a better understanding of the
physiopathology of these disorders and provide basis for their surgical and
clinical treatment.
PMID- 29349074
TI - Biomechanical Effects of Posterior Condylar Offset and Posterior Tibial Slope on
Quadriceps Force and Joint Contact Forces in Posterior-Stabilized Total Knee
Arthroplasty.
AB - This study aimed to determine the biomechanical effect of the posterior condylar
offset (PCO) and posterior tibial slope (PTS) in posterior-stabilized (PS) fixed
bearing total knee arthroplasty (TKA). We developed +/-1, +/-2, and +/-3 mm PCO
models in the posterior direction and -3 degrees , 0 degrees , 3 degrees , and 6
degrees PTS models using a previously validated FE model. The influence of
changes in the PCO and PTS on the biomechanical effects under deep-knee-bend
loading was investigated. The contact stress on the PE insert increased by 14%
and decreased by 7% on average as the PCO increased and decreased, respectively,
compared to the neutral position. In addition, the contact stress on post in PE
insert increased by 18% on average as PTS increased from -3 degrees to 6 degrees
. However, the contact stress on the patellar button decreased by 11% on average
as PTS increased from -3 degrees to 6 degrees in all different PCO cases. The
quadriceps force decreased by 14% as PTS increased from -3 degrees to 6 degrees
in all PCO models. The same trend was found in patellar tendon force. Changes in
PCO had adverse biomechanical effects whereas PTS increase had positive
biomechanical effects. However, excessive PTS should be avoided to prevent knee
instability and subsequent failure.
PMID- 29349075
TI - Influence of Restorative Materials on Color of Implant-Supported Single Crowns in
Esthetic Zone: A Spectrophotometric Evaluation.
AB - Restorations of 98 implant-supported single crowns in anterior maxillary area
were divided into 5 groups: zirconia abutment, titanium abutment, and gold/gold
hue abutment with zirconia coping, respectively, and titanium abutment with metal
coping as well as gold/gold hue abutment with metal coping. A reflectance
spectrophotometer was used to evaluate the color difference between the implant
crowns and contralateral/neighboring teeth, as well as the color difference
between the peri-implant soft tissue and the natural marginal mucosa. The mucosal
discoloration score was used for subjective evaluation of the esthetic outcome of
soft tissue around implant-supported single crowns in the anterior zone, and the
crown color match score was used for subjective evaluation of the esthetic
outcome of implant-supported restoration. ANOVA analysis was used to compare the
differences among groups and Spearman correlation was used to test the
relationships. A gold/gold hue abutment with zirconia coping was the best choice
for an esthetic crown and the all-ceramic combination was the best for peri
implant soft tissue. Significant correlation was found between the
spectrophotometric color difference of peri-implant soft tissue and mucosal
discoloration score, while no significant correlation was found between the total
spectrophotometric color difference of implant crown and crown color match score.
PMID- 29349076
TI - The Association between 5HT2A T102C and Behavioral and Psychological Symptoms of
Dementia in Alzheimer's Disease: A Meta-Analysis.
AB - The serotonin receptor gene (5-HT2A) has been reported to be a susceptible factor
in behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's
disease (AD). However, previous results were conflicting. We aim to investigate
the association of 5-HT2A T102C with BPSD in AD using a meta-analysis. Studies
were collected using PubMed, Web of Science, the Cochrane Library databases,
Chinese National Knowledge Infrastructure (CNKI), and Embase. Pooled odds ratios
(ORs) with 95% confidence intervals (CIs) were used to assess associations. Nine
studies with 1899 AD patients with/without BPSD were included in this meta
analysis. The 102C and CC genotypes were associated with psychosis in AD (102C: p
< 0.00001, OR [95% CI] = 3.19 [2.12-4.79]; CC: p < 0.00001, OR [95% CI] = 7.24
[3.60-14.59]). The TT genotype was significantly associated with hallucinations,
aberrant motor behavior, and psychosis in AD (hallucinations: p = 0.001, OR [95%
CI] = 0.52 [0.36-0.77]; aberrant motor behavior: p = 0.03, OR [95% CI] = 0.58
[0.35-0.95]; and psychosis: p = 0.002, OR [95% CI] = 0.34 [0.17-0.67]). No
association was observed between T102C alleles or genotypes and delusions,
agitation/aggression, depression, and apathy (p > 0.05). Thus, the 5HT2A T102C
might be a susceptible factor for hallucinations, aberrant motor behavior, and
psychosis in AD. The potential mechanism of this polymorphism in BPSD in AD
requires further exploration.
PMID- 29349077
TI - The Prognostic Value of HRAS mRNA Expression in Cutaneous Melanoma.
AB - This study aimed to investigate the prognostic value of HRAS mRNA expression in
cutaneous melanoma. Cutaneous melanoma is an aggressive cancer with an increasing
incidence. Few studies have focused on the transcriptional level of RAS isoforms
(KRAS, NRAS, and HRAS) in cutaneous melanoma. To gain further insight into RAS
isoforms at transcriptional level, we obtained the cutaneous melanoma data from
cBioPortal and investigated the RAS mRNA expression levels in different stages of
melanoma and evaluated their correlation with clinical characteristics and
patients' survival. Furthermore, we retrieved and analyzed the coexpression data
and performed pathway enrichment analysis. Totally, 452 cutaneous melanoma cases
were included in this study. We found that lower HRAS expression level was
associated with longer patient survival. 206 genes that negatively correlated
with HRAS expression were positively correlated with KRAS and NRAS expression. In
contrast, no gene that positively correlated with HRAS expression was positively
correlated with KRAS and NRAS expression. In conclusion, our data showed that
transcriptional regulation was different for the three RAS isoforms in cutaneous
melanoma. This study highlighted the prognostic value of HRAS mRNA expression and
revealed that HRAS greatly differs from KRAS and NRAS at the transcriptional
level.
PMID- 29349078
TI - Categorisation of Mobile EEG: A Researcher's Perspective.
AB - Researchers are increasingly attempting to undertake electroencephalography (EEG)
recordings in novel environments and contexts outside of the traditional static
laboratory setting. The term "mobile EEG," although commonly used to describe
many of these undertakings, is ambiguous, since it attempts to encompass a wide
range of EEG device mobility, participant mobility, and system specifications
used across investigations. To provide quantitative parameters for "mobile EEG,"
we developed a Categorisation of Mobile EEG (CoME) scheme based upon scoring of
device mobility (D, from 0, off-body, to 5, head-mounted with no additional
equipment), participant mobility (P, from 0, static, to 5, unconstrained
running), system specification (S, from 4, lowest, to 20, highest), and number of
channels (C) used. The CoME scheme was applied to twenty-nine published mobile
EEG studies. Device mobility scores ranged from 0D to 4D, participant mobility
scores from 0P to 4P, and system specification scores from 6S to 17S. The format
of the scores for the four parameters is given, for example, as (2D, 4P, 17S,
32C) and readily enables comparisons across studies. Our CoME scheme enables
researchers to quantify the degree of device mobility, participant mobility, and
system specification used in their "mobile EEG" investigations in a standardised
way.
PMID- 29349079
TI - Advances of Techniques in Deep Regional Blocks.
PMID- 29349080
TI - Comparative Analysis and Classification of Cassette Exons and Constitutive Exons.
AB - Alternative splicing (AS) is a major engine that drives proteome diversity in
mammalian genomes and is a widespread cause of human hereditary diseases. More
than 95% of genes in the human genome are alternatively spliced, and the most
common type of AS is the cassette exon. Recent discoveries have demonstrated that
the cassette exon plays an important role in genetic diseases. To discover the
formation mechanism of cassette exon events, we statistically analyze cassette
exons and find that cassette exon events are strongly influenced by individual
exons that are smaller in size and that have a lower GC content, more codon
terminations, and weaker splice sites. We propose an improved random-forest-based
hybrid method of distinguishing cassette exons from constitutive exons. Our
method achieves a high accuracy in classifying cassette exons and constitutive
exons and is verified to outperform previous approaches. It is anticipated that
this study will facilitate a better understanding of the underlying mechanisms in
cassette exons.
PMID- 29349081
TI - Quality of Life in Workers and Stress: Gender Differences in Exposure to
Psychosocial Risks and Perceived Well-Being.
AB - Background: Quality of working life is the result of many factors inherent in the
workplace environment, especially in terms of exposure to psychosocial risks.
Objectives: The purpose of this study is to assess the quality of life with
special attention to gender differences. Methods: The HSE-IT questionnaire and
the WHO-5 Well-Being Index were administered to a group of workers (74 males and
33 females). The authors also used Cronbach's alpha test to assess the internal
consistency of both questionnaires and the Mann-Whitney test to evaluate the
significance of gender differences in both questionnaires. Results: The HSE-IT
highlighted the existence of work-related stress in all the population with a
critical perception regarding the domain "Relationships." Furthermore, gender
analysis highlighted the presence of two additional domains in the female
population: "Demand" (p = 0,002) and "Support from Managers" (p = 0,287). The WHO
5 highlighted a well-being level below the standard cut-off point with a
significant gender difference (p = 0.009) for males (18, SD = 6) as compared to
females (14, SD = 6,4). Cronbach's alpha values indicated a high level of
internal consistency for both of our scales. Conclusions: The risk assessment of
quality of working life should take into due account the individual
characteristics of workers, with special attention to gender.
PMID- 29349082
TI - Efficacy of One-Year Treatment with Aflibercept for Diabetic Macular Edema with
Practical Protocol.
AB - The purpose of this study was to determine the efficacy of one-year treatment of
diabetic macular edema (DME) with intravitreal aflibercept (IVA) injections on a
practical protocol. The medical records of 51 eyes of 43 patients who were
diagnosed with DME and had received IVA treatments were reviewed. The best
corrected visual acuity (BCVA) and the central macular thickness (CMT) were
measured at the baseline and at 1, 3, 6, and 12 months after the IVA. The mean
number of IVA injections was 3.8 +/- 2.4. The mean BCVA was significantly better
and the CMT was thinner after the IVA at all follow-up times (P < 0.05). The BCVA
was better in eyes with a serous retinal detachment (SRD) than without a SRD (P <
0.01). There was a significant correlation between the photoreceptor outer
segment (PROS) length and BCVA at the baseline and at 12 months after the IVA (P
< 0.05). A fewer number of IVA injections significantly improved the BCVA and the
CMT in eyes with DME after one-year treatment. IVA was more effective in the SRD+
group than in the SRD- group. The PROS length may be a predictive marker for
visual outcomes after one-year treatment with IVA for DME (IRB#2272).
PMID- 29349083
TI - Effects of Two Current Great Saphenous Vein Thermal Ablation Methods on Visual
Analog Scale and Quality of Life.
AB - Background: The aim of the study is to compare the current two endovenous thermal
ablation methods by examining the effects on the visual analog scale (VAS) and
the short form-36(r) quality of life index. Methods: Ninety-six patients who
underwent unilateral endovenous thermal ablation of great saphenous vein were
included. ClosureFastTM catheters were used in the RFA group and 1470 nm radial
fiber laser catheters were used in the EVLA group. Results: The RFA group
consisted of 41 patients and the EVLA group consisted of 55 patients. The
preoperative baseline characteristics of both groups were similar. On the day of
operation, VAS values were 2.8 +/- 1.1 in the RFA group and 3.6 +/- 1.8 in the
EVLA group (p = 0.02). Comparisons of short form-36 parameters in both groups
showed them to be similar except the pain detected at postoperative 1st week
(48.1 +/- 5.4 for RFA, 44.9 +/- 7.6 for EVLA, p = 0.04). Conclusion: Results in
postprocedural quality of life were found to be similar in both of the
techniques. However, in terms of postoperative pain, radiofrequency ablation is
still superior to the 1470 nm radial fiber laser catheters.
PMID- 29349084
TI - In Vitro Biological Screening of Hartmannia rosea Extracts.
AB - The present study is focused on the assessment of the medicinal therapeutic
potential extracts of H. rosea to investigate their pharmacological implications
based upon science proofs. The antioxidant activity of fraction of H. rosea,
namely, n-hexane (HR-1), ethyl acetate (HR-2), chloroform (HR-3), and n-butanol
(HR-4), was performed by using the DPPH radical scavenging method. The
cytotoxicity and enzyme inhibition assessment were also performed. All the
extracts showed significant antioxidant, antibacterial, and protein kinase
inhibition but none of the extracts exhibited alpha-amylase inhibition activity.
The chloroform extract HR-3 may block a kinase receptor from binding to ATP; the
lead molecule will be isolated, which may stop cancerous cell growth and demotion
of cell division. It is predicted that ethyl acetate, chloroform, and n-butanol
extracts of H. rosea contain polyphenolics, flavonoids, and alkaloids that are
biologically effective candidates exhibiting significant cytotoxicity,
antioxidant, and antimicrobial activities. They may control oxidative damage in
the body tissues and act as potential antidiabetic and anticancer agents. These
studies will also be helpful for future drug designing and drug development
research.
PMID- 29349085
TI - Preimplantation Genetic Diagnosis for Myotonic Dystrophy Type 1 and Analysis of
the Effect of the Disease on the Reproductive Outcome of the Affected Female
Patients.
AB - Myotonic dystrophy type 1 (DM1) is the most common adult muscular dystrophy and
presents an autosomal dominant inheritance. A reproductive option for the
families affected is preimplantation genetic diagnosis (PGD). One limitation of
this option is the nonoptimal response to ovarian stimulation of the women with
DM1, although controversial results exist regarding this subject. In this study,
we have analyzed the results of the PGD program applied to DM1 at our
institution. A total of 35 couples have been included in our program since 2010,
and 59 cycles have been performed. The percentage of transfers per cycle was
64.4% and the live birth rate per cycle was 18.6%. Interestingly, statistically
significant differences were observed for the clinical results in the group of
couples with an affected female versus the group with an affected male or versus
a group of couples with different referral reasons. Specifically, both the
percentage of mature oocytes out of the total oocytes retrieved and the
percentage of fertilization were considerably lower in the group of DM1 females.
Our findings would suggest the possibility of achieving less favourable PGD
outcomes in women with DM1 in comparison with other pathologies, although the
underlying mechanism remains unknown.
PMID- 29349086
TI - Preparation of P3HB4HB/(Gelatin + PVA) Composite Scaffolds by Coaxial
Electrospinning and Its Biocompatibility Evaluation.
AB - This study was conducted to prepare coaxial electrospun scaffolds of
P3HB4HB/(gelatin + PVA) with various concentration ratios with P3HB4HB as the
core solution and gelatin + PVA mixture as the shell solution; the mass ratios of
gelatin and PVA in each 10 mL shell mixture were 0.6 g : 0.2 g (Group A), 0.4 g :
0.4 g (Group B), and 0.2 g : 0.6 g (Group C). The results showed that the pore
size, porosity, and cell proliferation rate of Group C were better than those of
Groups A and B. The ascending order of the tensile strength and modulus of
elasticity was Group A < Group B < Group C. The surface roughness was Group C >
Group B > Group A. The osteogenic and chondrogenic-specific staining showed that
Group C was stronger than Groups A and B. This study demonstrates that when the
mass ratio of gelatin : PVA was 0.2 g : 0.6 g, a P3HB4HB/(gelatin + PVA)
composite scaffold with a core-shell structure can be prepared, and the scaffold
has good biocompatibility that it may be an ideal scaffold for tissue
engineering.
PMID- 29349088
TI - Corrigendum to "Antidiabetic Effect of Young and Old Ethanolic Leaf Extracts of
Vernonia amygdalina: A Comparative Study".
AB - [This corrects the article DOI: 10.1155/2016/8252741.].
PMID- 29349087
TI - Advances and Current Concepts in the Medical Management of Gastroenteropancreatic
Neuroendocrine Neoplasms.
AB - Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare and
heterogeneous group of tumors presenting as localised or metastatic disease and
in a subset with distinct clinical syndromes. Treatment is aimed at controlling
the functional syndrome, eradicating the tumor, and/or preventing further tumor
growth. Surgery is the treatment of choice in removing the primary tumor and/or
reducing tumor burden but cannot be applied to all patients. Somatostatin analogs
(SS-analogs) obtain control of functional syndromes in the majority of GEP
neuroendocrine tumors (NETs); phase III trials have shown that SS-analogs can be
used as first-line antiproliferative treatment in patients with slow-growing GEP
NETs. The role of the recently approved serotonin inhibitor, telotristat ethyl,
and gastrin receptor antagonist, netazepide, is evolving. Streptozotocin-based
chemotherapy has been used for inoperable or progressing pancreatic NENs but the
orally administered combination of capecitabine/temozolomide is becoming more
popular due to its better tolerability and potential effect in other GEP-NENs.
Phase III trials have shown efficacy of molecular targeted therapies in GEP-NETs
and of radionuclide treatment in patients with midgut carcinoid tumors expressing
somatostatin receptors. Most patients will develop disease progression
necessitating further therapeutic options. A combination of currently available
treatments along with the molecular signature of each tumor will guide future
treatment.
PMID- 29349089
TI - Elevated Levels of Interferon-gamma Are Associated with High Levels of Epstein
Barr Virus Reactivation in Patients with the Intestinal Type of Gastric Cancer.
AB - Background: The inflammatory response directed against Helicobacter pylori (HP)
is believed to be one of the main triggers of the appearance of gastric lesions
and their progression to gastric cancer (GC). Epstein-Barr virus (EBV) has been
found responsible for about 10% of all GCs, but the inflammatory response has not
been studied in GC patients with evidence of high levels of EBV reactivation.
Objective: To determine the relationship between inflammation and antibodies
against EBV reactivation antigens, HP, and the bacterium virulence factor CagA in
patients with GC. Methods: 127 GC patients, 46 gastritis patients, and 197
healthy subjects were studied. IL-1beta, IL-6, IL-8, IL-10, TNF-alpha, TGF-beta,
MCP-1, and IFN-gamma levels were measured in serum or plasma and compared against
the antibody titers of VCA-IgG, HP, and the HP virulence factor CagA. Statistical
associations were estimated. Results: Significant ORs and positive trends were
found between VCA-IgG and IFN-gamma, specifically for patients with GC of
intestinal type (OR: 6.4, 95% C.I. 1.2-35.4) (p < 0.044). Conclusions: We
confirmed a positive association between a marker of EBV reactivation and
intestinal gastric cancer and present evidence of a correlation with elevated
serum levels of IFN-gamma, but not with the other cytokines.
PMID- 29349091
TI - Coexistent Ipsilateral Internal Carotid Artery Occlusion and Cerebral Venous
Thrombosis in Hepatitis C.
AB - A 58-year-old male, known to have hepatitis C virus (HCV), presented with
intermittent headaches and left-sided sensorimotor symptoms. There were no focal
neurological deficits on examination. Electrocardiogram was unremarkable.
Computed tomography angiography head and neck displayed extracranial right
internal carotid artery occlusion. Magnetic resonance imaging showed right
cortical vein thrombosis, with hemorrhagic infarction. Echocardiography with
bubble study was unremarkable. Hypercoagulable workup was significant for protein
S deficiency. He was treated with warfarin for 6 months. Repeat protein S levels
remained low 9 months later. The coexistence of arterial and venous thrombotic
events gives rise to a limited differential. In this case, it may be related to
chronic HCV infection. The underlying pathogenesis is not clear; however, it is
possible the patient had chronic high-grade internal carotid artery stenosis,
which occluded leading to his presenting symptoms. The cortical vein thrombosis
is likely an incidental finding here. The extent by which HCV contributed to the
cerebral thrombosis and carotid artery occlusion in our case is not clear;
however, the hypercoagulable and atherosclerotic properties of the virus cannot
be disregarded. The virus can promote carotid atherosclerosis and cerebral venous
thrombosis as well as other venous and arterial thromboembolic events.
Furthermore, HCV is associated with impaired venous flow and procoagulant
properties, which can fuel a hypercoagulable state. Also of note cirrhosis is
associated with protein S deficiency. We recommend considering an underlying
hypercoagulable state including both arterial and venous thrombosis in HCV
infection.
PMID- 29349090
TI - Dysregulation of miR-155-5p and miR-200-3p and the Anti-Non-Bilayer Phospholipid
Arrangement Antibodies Favor the Development of Lupus in Three Novel Murine Lupus
Models.
AB - Systemic lupus erythematosus (SLE) is characterized by deregulated activation of
T and B cells, autoantibody production, and consequent formation of immune
complexes. Liposomes with nonbilayer phospholipid arrangements (NPA), induced by
chlorpromazine, procainamide, or manganese, provoke a disease resembling human
lupus when administered to mice. These mice produce anti-NPA IgM and IgG
antibodies and exhibit an increased number of TLR-expressing spleen cells and a
modified gene expression associated with TICAM1-dependent TLR-4 signaling
(including IFNA1 and IFNA2) and complement activation. Additionally, they showed
a diminished gene expression related to apoptosis and NK cell activation. We
hypothesized that such gene expression may be affected by miRNAs and so miRNA
expression was studied. Twelve deregulated miRNAs were found. Six of them were
common to the three lupus-like models. Their validation by qRT-PCR and TaqMan
probes, including miR-342-3p, revealed that miR-155-5p and miR-200a-3p expression
was statistically significant. Currently described functions for these miRNAs in
autoimmune diseases such as SLE reveal their participation in inflammation,
interferon production, germinal center responses, and antibody maturation. Taking
into account these findings, we propose miR-155-5p and miR-200a-3p, together with
the anti-NPA antibodies, as key players in the murine lupus-like models and
possible biomarkers of the human SLE.
PMID- 29349092
TI - Cathepsin B plays a key role in optimal production of the influenza A virus.
AB - Background: Influenza A virus (IAV) is the etiologic agent of the febrile
respiratory illness, commonly referred to as 'flu'. The lysosomal protease
cathepsin B (CTSB) has shown to be involved in the lifecycle of various viruses.
Here, we examined the role of CTSB in the IAV lifecycle. Methods: CTSB-deficient
(CTSB-/-) macrophages and the human lung epithelial cell line A549 cells treated
with CA-074Me were infected with the A/Puerto Rico/8/34 strain of IAV (IAV-PR8).
Viral entry and propagation were measured through quantitative real-time RT-PCR;
production and localization of hemagglutinin (HA) protein in the infected host
cells were analysed by Western blots, flow cytometry and confocal microscopy;
production of progeny viruses were measured by a hemagglutination assay. Results:
CTSB-/- macrophages and CA-074Me-treated A549 cells had no defects in
incorporating IAV-PR8 virions and permitting viral RNA synthesis. However, these
cells produced significantly lower amounts of HA protein and progeny virions than
wild-type or untreated cells. Conclusion: These data indicate that CTSB is
involved in the expression of IAV-PR8 HA protein and subsequent optimal
production of IAV-PR8 progeny virions. Targeting CTSB can be a novel therapeutic
strategy for treating IAV infection.
PMID- 29349093
TI - Preseason Adductor Squeeze Strength in 303 Spanish Male Soccer Athletes: A Cross
sectional Study.
AB - Background: Hip adductor muscle weakness and a history of groin injury both have
been identified as strong risk factors for sustaining a new groin injury. Current
groin pain and age have been associated with hip adductor strength. These factors
could be related, but this has never been investigated. Purpose: To investigate
whether soccer athletes with past-season groin pain and with different durations
of past-season groin pain had lower preseason hip adductor squeeze strength
compared with those without past-season groin pain. We also investigated whether
differences in preseason hip adductor squeeze strength in relation to past-season
groin pain and duration were influenced by current groin pain and age. Study
Design: Cross-sectional study; Level of evidence, 3. Methods: In total, 303 male
soccer athletes (mean age, 23 +/- 4 years; mean weight, 74.0 +/- 7.9 kg; mean
height, 178.1 +/- 6.3 cm) were included in this study. Self-reported data
regarding current groin pain, past-season groin pain, and duration were
collected. Hip adductor squeeze strength was obtained using 2 different reliable
testing procedures: (1) the short-lever (resistance placed between the knees,
feet at the examination bed, and 45 degrees of hip flexion) and (2) the long
lever (resistance placed between the ankles and 0 degrees of hip flexion)
squeeze tests. Results: There was no difference between those with (n = 123) and
without (n = 180) past-season groin pain for hip adductor squeeze strength when
adjusting for current groin pain and age. However, athletes with past-season
groin pain lasting longer than 6 weeks (n = 27) showed 11.5% and 15.3% lower
values on the short-lever (P = .006) and long-lever (P < .001) hip adductor
squeeze strength tests, respectively, compared with those without past-season
groin pain. Conclusion: Male soccer athletes with past-season groin pain lasting
longer than 6 weeks are likely to begin the next season with a high-risk groin
injury profile, including a history of groin pain and hip adduction weakness.
PMID- 29349094
TI - Upper Extremity Functional Status of Female Youth Softball Pitchers Using the
Kerlan-Jobe Orthopaedic Clinic Questionnaire.
AB - Background: Softball is a popular sport with a high incidence of upper extremity
injuries. The Kerlan-Jobe Orthopaedic Clinic (KJOC) questionnaire is a validated
performance and functional assessment tool used in overhead athletes. Upper
extremity pain patterns and baseline KJOC scores have not been reported for
active female youth softball pitchers. Purpose/Hypothesis: The purpose of this
study was to establish the prevalence of upper extremity pain and its effect in
female youth softball pitchers over a competitive season. We hypothesized that
participants who missed time due to injury in the past year would have lower KJOC
scores. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Fifty
three female softball pitchers aged 12 to 18 years were recruited from softball
clinics in Vancouver, British Columbia, Canada. All participants self-identified
as a pitcher on a competitive travel team. Participants were administered the
KJOC questionnaire before and during the playing season. Missed time due to
injury in the past year, current pain patterns, and KJOC scores were primary
outcomes. Results: The mean (+/-SD) preseason KJOC score was 87.2 +/- 10.6. In
the preseason, 22.6% of pitchers reported playing with arm trouble, and 32.1%
missed time due to injury in the past year. The mean KJOC score for pitchers
reporting a previous injury (n = 17) was significantly lower compared with those
without an injury (n = 36) (79.5 +/- 13.8 vs 90.9 +/- 6.2, respectively; P =
.02). The posterior shoulder was the most commonly reported pain location. For
the cohort completing the questionnaire both before and during the playing season
(n = 35), mean KJOC scores did not change significantly over the playing season
(P = .64). Lower preseason KJOC scores were significantly related to the in
season injury risk (P = .016). Pitchers with a preseason score of less than 90
had a 3.5 (95% CI, 1.1-11.2) times greater risk of reporting an in-season injury.
Conclusion: Female youth softball pitchers have a high baseline functional
status. However, 1 in 3 pitchers reported missed time due to injury in the
previous year, and shoulder pain was more prevalent than elbow pain. The KJOC
questionnaire can be used by coaches, researchers, and clinicians to identify
youth softball pitchers at risk for injuries who may benefit from interventions.
PMID- 29349095
TI - Spinal Motocross Injuries in the United Kingdom.
AB - Background: Motocross is a form of motorcycle racing held on established off-road
circuits and has been a recreational and competitive sport across the world for
>100 years. In the United Kingdom alone, motocross has grown into a phenomenally
ambitious and popular franchise. There are >200 motocross clubs across the
country, permitting >900 events annually. Purpose: To assess the current trend of
spine-related motocross injuries over the past 5 years. Study Design: Descriptive
epidemiology study. Methods: Data were prospectively collected over 5 years
(August 2010-August 2015) at our regional trauma and spine unit, regardless of
whether the rider was performing the sport competitively or recreationally.
Results: During the study period, spine-related injuries were identified for 174
patients (age range, 6-75 years) who were directly referred to our department
following recreational or competitive motocross, with most injuries being
sustained within the early spring and summer months, representing the start of
the motocross season. A significant number of injuries were in males (n = 203,
94%), with the majority of injuries occurring within the 21- to 30-year-old age
group. A total of 116 (54%) injuries required operative treatment. The most
common spinal injury was thoracolumbar burst fracture (n = 95), followed by
chance fractures (n = 26). Conclusion: This data series emphasizes the prevalence
and devastation of motocross-related spinal injuries in the United Kingdom and
may serve in administering sanctions and guidelines to governing bodies of
motocross. The spinal injuries that occur during motocross have significant
capital connotations for regional spinal centers. The recent surge in motocross
popularity is correlated with the number of injuries, which have increased over
the past 5 years by almost 500%.
PMID- 29349097
TI - Universal Method for the Purification of Recombinant AAV Vectors of Differing
Serotypes.
AB - The generation of clinical good manufacturing practices (GMP)-grade adeno
associated virus (AAV) vectors requires purification strategies that support the
generation of vectors of high purity, and that exhibit a good safety and efficacy
profile. To date, most reported purification schemas are serotype dependent,
requiring method development for each AAV gene therapy product. Here, we describe
a platform purification process that is compatible with the purification of
multiple AAV serotypes. The method generates vector preparations of high purity
that are enriched for capsids with full vector genomes, and that minimizes the
fractional content of empty capsids. The two-column purification method, a
combination of affinity and ion exchange chromatographies, is compatible with a
range of AAV serotypes generated by either the transient triple transfection
method or the more scalable producer cell line platform. In summary, the
adaptable purification method described can be used for the production of a
variety of high-quality AAV vectors suitable for preclinical testing in animal
models of diseases.
PMID- 29349098
TI - Comparison of HIV Testing among Children and Adults with Tuberculosis, Vietnam.
AB - HIV testing among persons with tuberculosis (TB) results in high-yield
identification of persons infected with HIV. To evaluate differences in HIV
testing among children versus adults with TB in Vietnam, we collected and
analyzed age-disaggregated facility and aggregated provincial data from the
National Tuberculosis Program. HIV testing was incompletely documented for >70%
of children, whereas adult testing data were >90% complete. Standardized training
of personnel for universal HIV testing and documentation for children with TB
could improve HIV case-detection and permit linking of children with HIV to
antiretroviral treatment to prevent morbidity and mortality.
PMID- 29349096
TI - Safety and Efficacy of AAV Retrograde Pancreatic Ductal Gene Delivery in Normal
and Pancreatic Cancer Mice.
AB - Recombinant adeno-associated virus (rAAV)-mediated gene delivery shows promise to
transduce the pancreas, but safety/efficacy in a neoplastic context is not well
established. To identify an ideal AAV serotype, route, and vector dose and assess
safety, we have investigated the use of three AAV serotypes (6, 8, and 9)
expressing GFP in a self-complementary (sc) AAV vector under an EF1alpha promoter
(scAAV.GFP) following systemic or retrograde pancreatic intraductal delivery.
Systemic delivery of scAAV9.GFP transduced the pancreas with high efficiency, but
gene expression did not exceed >45% with the highest dose, 5 * 1012 viral genomes
(vg). Intraductal delivery of 1 * 1011 vg scAAV6.GFP transduced acini, ductal
cells, and islet cells with >50%, ~48%, and >80% efficiency, respectively, and
>80% pancreatic transduction was achieved with 5 * 1011 vg. In a KrasG12D-driven
pancreatic cancer mouse model, intraductal delivery of scAAV6.GFP targeted acini,
epithelial, and stromal cells and exhibited persistent gene expression 5 months
post-delivery. In normal mice, intraductal delivery induced a transient increase
in serum amylase/lipase that resolved within a day of infusion with no sustained
pancreatic inflammation or fibrosis. Similarly, in PDAC mice, intraductal
delivery did not increase pancreatic intraepithelial neoplasia
progression/fibrosis. Our study demonstrates that scAAV6 targets the
pancreas/neoplasm efficiently and safely via retrograde pancreatic intraductal
delivery.
PMID- 29349099
TI - Repetitive Questioning Exasperates Caregivers.
AB - Repetitive questioning is due to an impaired episodic memory and is a frequent,
often presenting, problem in patients with Alzheimer's disease (amnestic type).
It is due to the patients' difficulties learning new information, retaining it,
and recalling it, and is often aggravated by a poor attention span and easy
distractibility. A number of factors may trigger and maintain repetitive
questioning. Caregivers should try to identify and address these triggers. In the
case discussion presented, it is due to the patient's concerns about her and her
family's safety triggered by watching a particularly violent movie aired on TV.
What went wrong in the patient/caregiver interaction and how it could have been
avoided or averted are explored. Also reviewed are the impact of repetitive
questioning, the challenges it raises for caregivers, and some effective
intervention strategies that may be useful to diffuse the angst that caregivers
experience with repetitive questioning.
PMID- 29349100
TI - Vitamin D Deficiency Associated With Markers of Cardiovascular Disease in
Children With Obesity.
AB - Adult studies have reported associations of low 25-hydroxyvitamin D (25OHD) with
dyslipidemia and cardiovascular disease; however, there are scarce pediatric data
regarding relationships between vitamin D status and specific lipid markers
affecting cardiovascular risk. In this cross-sectional study of children
evaluated at university-based pediatric endocrinology clinics, 178 patients
meeting criteria for overweight or obesity had 25OHD levels assessed over a 2
year period; 60 of 178 had non-HDL (high-density lipoprotein) cholesterol and
fasting lipid parameters performed. Patients with 25OHD <20 ng/mL had
significantly higher non-HDL cholesterol (134.76 +/- 47.32 vs 108.85 +/- 31.14, P
< .03), triglyceride (TG)/HDL ratio (3.09 +/- 2.26 vs 1.82 +/- 1.18, P = .03),
total cholesterol (TC)/HDL ratio (4.23 +/- 1.23 vs 3.40 +/- 1.05, P < .01), TC
(184.15 +/- 40.19 vs 158.89 +/- 30.10, P < .01), and TG (134.76 +/- 47.32 vs
78.93 +/- 37.46, P < .03) compared with 25OHD >=20 ng/mL. Vitamin D deficiency
was significantly associated with increase in atherogenic lipids and markers of
early cardiovascular disease. These findings suggest that vitamin D deficiency
may have negative effects on lipid parameters with increase in cardiovascular
risk.
PMID- 29349101
TI - Multilayered complex network datasets for three supply chain network archetypes
on an urban road grid.
AB - This article presents the multilayered complex network formulation for three
different supply chain network archetypes on an urban road grid and describes how
500 instances were randomly generated for each archetype. Both the supply chain
network layer and the urban road network layer are directed unweighted networks.
The shortest path set is calculated for each of the 1 500 experimental instances.
The datasets are used to empirically explore the impact that the supply chain's
dependence on the transport network has on its vulnerability in Viljoen and
Joubert (2017) [1]. The datasets are publicly available on Mendeley (Joubert and
Viljoen, 2017) [2].
PMID- 29349102
TI - Data on the clinical usefulness of brachial-ankle pulse wave velocity in patients
with suspected coronary artery disease.
AB - Brachial-artery pulse wave velocity (baPWV) is a simple and reliable tool for
measurement of arterial stiffness. Our previous studies suggested that baPWV is
associated with the presence and severity of coronary artery disease (CAD) and
the risk of cardiovascular events. In the present data article, we provided
supplementary data supporting the independent prognostic value of arterial
stiffness, assessed by baPWV, in patients with suspected CAD (Hwang et al., 2017)
[1]. The data was obtained from 523 patients undergoing coronary CT angiography
(CCTA), and baPWV was measured at the time of CCTA. Patients with vulnerable
coronary plaque or obstructive CAD on CCTA had higher age, more cardiovascular
risk factors, and higher baPWV values. Given the significant association between
high baPWV and the presence of vulnerable plaque or obstructive CAD as shown in
this data article, the prognostic value of baPWV was further assessed in
subgroups divided according to the CCTA findings (vulnerable plaque or
obstructive CAD). In each subgroup by CCTA findings, multivariable Cox
proportional hazard model analysis showed that high baPWV was an independent risk
factor for cardiovascular events even after adjusting for clinical risk factors.
PMID- 29349103
TI - Wildfire spread, hazard and exposure metric raster grids for central Catalonia.
AB - We provide 40 m resolution wildfire spread, hazard and exposure metric raster
grids for the 0.13 million ha fire-prone Bages County in central Catalonia
(northeastern Spain) corresponding to node influence grid (NIG), crown fraction
burned (CFB) and fire transmission to residential houses (TR). Fire spread and
behavior data (NIG, CFB and fire perimeters) were generated with fire simulation
modeling considering wildfire season extreme fire weather conditions (97th
percentile). Moreover, CFB was also generated for prescribed fire (Rx) mild
weather conditions. The TR smoothed grid was obtained with a geospatial analysis
considering large fire perimeters and individual residential structures located
within the study area. We made these raster grids available to assist in the
optimization of wildfire risk management plans within the study area and to help
mitigate potential losses from catastrophic events.
PMID- 29349104
TI - Dataset demonstrating effects of momentum transfer on sizing of current collector
for lithium-ion batteries during laser cutting.
AB - Material properties of copper and aluminum required for the numerical simulation
are presented. Electrodes used for the (paper) are depicted. This study describes
the procedures of how penetration depth, width, and absorptivity are obtained
from the simulation. In addition, a file format extracted from the simulation to
visualize 3D distribution of temperature, velocity, and melt pool geometry is
presented.
PMID- 29349105
TI - Draft genome sequence of Brevibacterium epidermidis EZ-K02 isolated from
nitrocellulose-contaminated wastewater environments.
AB - Brevibacterium spp. are aerobic, nonbranched, asporogenous, gram-positive, rod
shaped bacteria which may exhibit a rod-coccus cycle when cells get older and can
be found in various environments. Several Brevibacterium species have industrial
importance and are capable of biotransformation of various contaminants. Here we
describe the draft genome sequence of Brevibacterium epidermidis EZ-K02 isolated
from nitrocellulose-contaminated wastewater environments. The genome comprises
3,885,924 bp, with a G + C content of 64.2%. This whole genome shotgun project
has been deposited at DDBJ/ENA/GenBank under the accession PDHL00000000.
PMID- 29349106
TI - The wildland-urban interface raster dataset of Catalonia.
AB - We provide the wildland urban interface (WUI) map of the autonomous community of
Catalonia (Northeastern Spain). The map encompasses an area of some 3.21 million
ha and is presented as a 150-m resolution raster dataset. Individual housing
location, structure density and vegetation cover data were used to spatially
assess in detail the interface, intermix and dispersed rural WUI communities with
a geographical information system. Most WUI areas concentrate in the coastal belt
where suburban sprawl has occurred nearby or within unmanaged forests. This
geospatial information data provides an approximation of residential housing
potential for loss given a wildfire, and represents a valuable contribution to
assist landscape and urban planning in the region.
PMID- 29349107
TI - Draft genome sequence of Xylaria sp., the causal agent of taproot decline of
soybean in the southern United States.
AB - The draft genome of Xylaria sp. isolate MSU_SB201401, causal agent of taproot
decline of soybean in the southern U.S., is presented here. The genome assembly
was 56.7 Mb in size with an L50 of 246. A total of 10,880 putative protein
encoding genes were predicted, including 647 genes encoding carbohydrate-active
enzymes and 1053 genes encoding secreted proteins. This is the first draft genome
of a plant-pathogenic Xylaria sp. associated with soybean. The draft genome of
Xylaria sp. isolate MSU_SB201401 will provide an important resource for future
experiments to determine the molecular basis of pathogenesis.
PMID- 29349108
TI - Spatially and temporally continuous estimates of annual total nitrogen deposition
over North America, 1860-2013.
AB - This report describes the North American Climate Integration and Diagnostics -
Nitrogen Deposition Version 1 (NACID-NDEP1) database. The database contains
estimates of annual total nitrogen (N) deposition for the purpose of supporting
terrestrial ecosystem modelling in North America. It was constructed at 1-km
resolution with coverage of Alaska, Canada, and the conterminous U.S., with
continuous annual coverage from 1860 to 2013. Estimates were produced by
acquiring and compiling best-available data sources: Wet N deposition was
estimated from interpolation of monthly ammonium and nitrate concentration
measurements and from grids of monthly precipitation. Dry N deposition was
estimated from satellite measurements of ammonium and nitrogen oxides. Total N
deposition for the pre-industrial era was derived from previous modelling
studies. As these source datasets covered different time periods, several
assumptions were required to produce a continuous record.
PMID- 29349109
TI - Data collected in an integrated ecological survey of rotifer communities and
corresponding environmental variables in the highly polluted Haihe River Basin,
China.
AB - Here we presented two datasets (biological and environmental datasets) collected
in a comprehensive large geographical scale (approximately 1.1*105 km2) survey of
rivers/streams in the Haihe River Basin (HRB), which has become the most polluted
river basin in past two decades in China. The survey selected a total of 94
representative sampling sites in the plain region of HRB, where environmental
pollution is more severe than the mountain region. The biological dataset
contains the information on the identified rotifer species and their abundance,
while the environmental dataset provides the measured environmental variables at
each sampling site. Based on this ecological survey, we identified a total of 91
rotifer species and their abundance, as well as abundance of two crucial
taxonomic groups on rotifers' food webs (i.e., protozoans and crustaceans), and
also presented seven environmental variables, particularly those associated with
nitrogen and phosphorus pollution.
PMID- 29349110
TI - Data on assessment of groundwater quality for drinking and irrigation in rural
area Sarpol-e Zahab city, Kermanshah province, Iran.
AB - In present study 30 groundwater samples were collected from Sarpol-e Zahab area,
Kermanshah province of Iran in order to assess the quality of groundwater in
subjected area and determining its suitability for drinking and agricultural
purposes. Also the variations in the quality levels of groundwater were compared
over the years of 2015 and 2016. Statistical analyses including Spearman
correlation coefficients and factor analysis display good correlation between
physicochemical parameters (EC, TDS and TH) and Na+, Mg2+, Ca2+, Cl- and
[Formula: see text] ionic constituents. Also in order to assess water quality for
irrigation we used the United States Department of Agriculture (USDA)
classification which is based on SAR for irrigation suitability assessment. In
addition, the residual sodium carbonate (RSC), %Na, PI, KR, SSP, MH, EC
characteristics were calculated for all samples and used for assessment of
irrigation suitability. Based on these indicators, for every two years, the
quality of water for agriculture is in good and excellent category. The Piper
classification for hydro geochemical facies indicates that the water in the study
area is of Ca-HCO3- type. However, the study of water hardness shows that more
than 80% of samples are in hard and very hard water class. Therefore, there is a
need for decisions to refine and soften the water.
PMID- 29349111
TI - Slowly progressive chest rash in an elderly woman.
PMID- 29349112
TI - An immunosuppressed man with an isolated necrotic plaque on the chest.
PMID- 29349113
TI - Conjunctivitis, mucosal erosions, and moist cutaneous plaques.
PMID- 29349114
TI - Evaluation of a new venous catheter blood draw device and its impact on specimen
hemolysis rates.
AB - Objectives: Blood collections from peripheral intravenous catheters offer several
benefits to patients, including reduced needle punctures and patient discomfort,
but they risk reducing the quality of blood specimens analyzed by the laboratory.
In an effort to balance analytical quality of test results with patient-centered
care initiatives, a needle-less blood collection device called PIVOTM was
evaluated at two institutions. The primary objective of this study was to assess
the ability of the PIVOTM device to provide high-quality blood specimens for
laboratory testing compared to current blood collection methods. Methods: Blood
specimens drawn using the PIVOTM device were prospectively flagged. A
retrospective review was performed comparing the degree and rate of hemolysis for
PIVOTM blood collections to both concurrent and historical hemolysis rates for
other collection methods. Results: Approximately 7600 PIVOTM blood draws were
performed across the two institutions. The hemolysis rates of samples collected
with PIVOTM were evaluated using 2380 flagged collections, containing
approximately 1200 test orders requiring hemolysis index measurements. The
hemolysis rate of PIVOTM-flagged samples (1.8%) was statistically superior to the
venipuncture and central line blood collection methods (3.3%), reducing the risk
of hemolysis during a venous blood draw by 39%. Conclusions: PIVOTM collections
facilitated improvement in the rate and degree of sample hemolysis when compared
to venipuncture and central line blood collections. These findings suggest that
PIVOTM is capable of delivering samples that are superior to current blood
collection methods in terms of hemolysis rate as well as reducing the number of
invasive venipunctures required for laboratory testing.
PMID- 29349116
TI - Does an advantageous occupational position make women happier in contemporary
Japan? Findings from the Japanese Study of Health, Occupation, and Psychosocial
Factors Related Equity (J-HOPE).
AB - Occupational position is one of the determinants of psychological health, but
this association may differ for men and women depending on the social context. In
contemporary Japanese society, occupational gender segregation persists despite
increased numbers of women participating in the labour market, which may
contribute to gender specific patterns in the prevalence of poor psychological
health. The present study examined gender specific associations between
occupational position and psychological health in Japan, and the potential
mediating effects of job control and effort-reward imbalance in these
associations. We used data obtained from 7123 men and 2222 women, aged between 18
and 65 years, who participated in an occupational cohort study, the Japanese
Study of Health, Occupation, and Psychosocial Factors Related Equity (J-HOPE),
between 2011 and 2012. We used logistic regression to examine the association
between occupational position and poor psychological health, adjusted for age,
working hours, household income and education, as well as psychosocial work
characteristics (job control and effort-reward imbalance). The prevalence of poor
psychological health increased from manual/service occupations (23%) to
professionals/managers (38%) among women, while it did not vary by occupational
position among men. In women, the significant association between occupational
position and psychological health was not explained by job control, but was
attenuated by effort-reward imbalance. Our findings suggest that Japanese women
in more advantaged occupational positions are likely to be at a greater risk for
poor psychological health due to higher levels of effort-reward imbalance at
work.
PMID- 29349115
TI - Social connections and suicidal behaviour in young Australian adults: Evidence
from a case-control study of persons aged 18-34 years in NSW, Australia.
AB - Purpose: There is evidence that social isolation is a risk factor for suicide,
and that social connections are protective. Only a limited number of studies have
attempted to correlate the number of social connections a person has in their
life and suicidal behaviour. Method: Two population-based case-control studies of
young adults (18-34 years) were conducted in New South Wales, Australia. Cases
included both suicides (n=84) and attempts (n=101). Living controls selected from
the general population were matched to cases by age-group and sex. Social
connections was the main exposure variable (representing the number of
connections a person had in their life). Suicide and attempts as outcomes were
modelled separately and in combination using conditional logistic regression
modelling. The analysis was adjusted for marital status, socio-economic status,
and diagnosis of an affective or anxiety disorder. Results: Following adjustment
for other variables, those who had 3-4 social connections had 74% lower odds of
suicide deaths or attempts (OR=0.26, 95% CI 0.08, 0.84, p=0.025), and those with
5-6 connections had 89% lower odds of suicide deaths or attempts (OR=0.11 95% CI
0.03, 0.35, p<0.001), compared to those with 0-2 social connections. With the
number of social connection types specified as a continuous variable, the odds
ratio was 0.39 per connection (95% CI 0.27, 0.56, p<0.001). Conclusions: A
greater number of social connections was significantly associated with reduced
odds of suicide or attempt. This suggests that suicide prevention initiatives
that promote increased social connections at an individual, familial, and wider
social levels might be effective.
PMID- 29349117
TI - The double burden of malnutrition in Indonesia: Social determinants and
geographical variations.
AB - The presence of simultaneous under- and over-nutrition has been widely documented
in low- and middle-income countries, but global nutritional research has seen
only a few large-scale population studies from Indonesia. We investigate the
social determinants as well as the geographical variations of under- and over
nutrition in Indonesia using the largest public health study ever conducted in
the country, the National Basic Health Research 2007 (N=645,032). Multilevel
multinomial logistic regression and quantile regression models are fitted to
estimate the association between nutritional status and a number of socio
economic indicators at both the individual and district levels. We find that: (1)
education and income reduce the odds of being underweight by 10-30% but at the
same time increase those of overweight by 10-40%; (2) independent from the
compositional effect of poverty, income inequality is detrimental to population
health: a 0.1 increase in the Gini coefficient is associated with an 8-12%
increase in the odds of an individual's being both under- and overweight; and (3)
the effects that these determinants have upon nutritional status are not
necessarily homogeneous along the continuum of body mass index. Equally
important, our analysis reveals that there is substantial spatial clustering of
areas with elevated risk of under- or over-nutrition across the 17,000-island
archipelago. As of 2007, under-nutrition in Indonesia remains a 'disease of
poverty', while over-nutrition is one of affluence. The income inequality
accompanying Indonesia's economic growth may aggravate the dual burden of under-
and over-nutrition. A more equitable economic policy and a policy that improves
living standards may be effective for addressing the double burden.
PMID- 29349118
TI - Assessing the relationship between dental appearance and the potential for
discrimination in Ontario, Canada.
AB - Poor oral health is influenced by a variety of individual and structural factors.
It disproportionately impacts socially marginalized people, and has implications
for how one is perceived by others. This study assesses the degree to which
residents of Canada's most populated province, Ontario, recognize income-related
oral health inequalities and the degree to which Ontarians blame the poor for
these differences in health, thus providing an indirect assessment of the
potential for prejudicial treatment of the poor for having bad teeth. Data were
used from a provincially representative survey conducted in Ontario, Canada in
2010 (n=2006). The survey asked participants questions about fifteen specific
conditions (e.g. dental decay, heart disease, cancer) for which inequalities have
been described in Ontario, and whether participants agreed or disagreed with
various statements asserting blame for differences in health between social
groups. Binary logistic regression was used to determine whether assertions of
blame for differences in health are related to perceptions of oral health
conditions. Oral health conditions are more commonly perceived as a problem of
the poor when compared to other diseases and conditions. Among those who
recognize that oral conditions more commonly affect the poor, particular
socioeconomic and demographic characteristics predict the blaming of the poor for
these differences in health, including sex, age, education, income, and political
voting intention. Social and economic gradients exist in the recognition of, and
blame for, oral health conditions among the poor, suggesting a potential for
discrimination amongst socially marginalized groups relative to dental
appearance. Expanding and improving programs that are targeted at improving the
oral and dental health of the poor may create a context that mitigates
discrimination.
PMID- 29349119
TI - The effect of deworming on early childhood development in Peru: A randomized
controlled trial.
AB - Background: There is a knowledge gap on the effect of early childhood deworming
on development in low- and middle-income countries. This evidence is important in
the critical window of growth and development before two years of age. Methods: A
randomized controlled trial of the benefit, and optimal timing and frequency, of
deworming on development was conducted in Iquitos, Peru. Children were enrolled
during routine 12-month growth and development visits and randomly allocated to:
(1) deworming at the 12-month visit and placebo at the 18-month visit; (2)
placebo at the 12-month visit and deworming at the 18-month visit; (3) deworming
at the 12 and 18-month visits; or (4) placebo at the 12 and 18-month visits. The
Bayley Scales of Infant Development III was used to assess cognitive, language
and motor skills at the 12 and 24-month visits. One-way ANOVA analyses used an
intention-to-treat approach. Results: Between September 2011 and June 2012, 1760
children were enrolled. Attendance at the 24-month visit was 88.8% (n=1563). Raw
scores on all subtests increased over 12 months; however, cognitive and
expressive language scaled scores decreased. There was no statistically
significant benefit of deworming, or effect of timing or frequency, on any of the
development scores. Baseline height and weight and maternal education were
associated with development scores at 24 months. Conclusions: After 12 months of
follow-up, an overall benefit of deworming on cognition, language or fine motor
development was not detected. Additional integrated child and maternal
interventions should be considered to prevent developmental deficits in this
critical period.
PMID- 29349120
TI - Trajectories and predictors of alcohol consumption over 21 years of mothers'
reproductive life course.
AB - Introduction: Little is known about the patterns of women's alcohol consumption
over their reproductive life course. This study identifies trajectories of
alcohol consumption by mothers over 21 years of their reproductive life course
and examines baseline predictors of these trajectories. Methods: Data were
obtained from a prospective cohort study of 3715 women in Brisbane, Queensland,
Australia over 21 years of follow-up. Women's alcohol consumption was measured by
frequency and quantity of use across the surveys. Potential predictors and
confounding variables were assessed at baseline. Group based-trajectory modelling
was used to identify typical drinking trajectories over the maternal reproductive
life course. Multinomial logistic regression was employed to examine predictors
associated with these trajectories. Results: Four trajectories of alcohol
consumption were indentified for mothers over the 21-year period. These
trajectories included abstainers (11.9%), low-stable drinkers (58.0%), moderate
escalating drinkers (25.3%), and heavy-escalating drinkers (4.8%). After
adjustment for significant covariates, membership of the abstaining trajectory
was predicted by lower family income, being married, and high frequency of church
attendance while membership of the heavier-escalating trajectory was associated
with women who were not currently married, never went church and had unhealthy
lifestyle behaviours. Conclusions: Patterns of women's alcohol consumption
exhibit a high level of stability for abstainers and women who drink at low
levels. After the birth of their child, there are some changes in alcohol
consumption for the moderate and heavy-escalating alcohol consumption groups. Low
risk patterns of consumption are associated with variables which generally
reflected a low risk behaviour lifestyle. Intervention programmes should
particularly target women engaging in the heavy-escalating alcohol consumption
group as this group increase their consumption shortly after the birth of their
child. There is a need to understand more about the social and health
consequences to mothers and their children of being in the moderate and heavy
escalating drinking trajectory groups.
PMID- 29349121
TI - Adherence to clinical preventive services guidelines: Population-based online
randomized trial.
AB - The Patient Protection and Affordable Care Act (ACA) addresses use of clinical
preventive services relative to evidence-based guidelines by mandating that most
health insurance plans provide coverage without cost-sharing for services that
receive an A or B rating. However, knowledge about and positive attitudes towards
guidelines are extremely low. This study was a population-based randomized
experiment to examine beliefs about and intentions to adhere to screening
guidelines for the Prostate Specific Antigen (PSA) and Pap tests. The study had
two objectives: (1) test reactions to and understanding of guidelines, and (2)
experimentally compare receptivity to messages to promote PSA and Pap test
recommendations. We first surveyed a population-based sample of (1) US adults age
18 and over, (2) subsample of women aged 65 or younger, (3) subsample of men aged
40 or older. A sample of 2923 completed an initial questionnaire. Next a subset
of participants meeting eligibility criteria were recruited from the population
based sample into a message testing experiment: (1) women aged 65 or younger, (2)
and men aged 40 or older. Participants meeting these eligibility requirements
were randomized to gain, loss, or balanced PSA (men) or Pap test (women) message
stimulus conditions and followed for 8 weeks. Data were collected through the GfK
Custom Research panel. A total of 2401 were eligible, 2321 completed the
baseline, and 1730 completed follow up. Mixed effect regression models revealed
that higher receptivity to messages was associated with greater intentions to
seek cancer information and to speak to a Doctor about PSA and Pap tests. The
loss frame was associated with higher intentions to speak to friends and family
about PSA and Pap tests. Finally, perceived importance and personal understanding
of guidelines predicted intentions to seek more information about them. This
study contributes to evidence on how best to inform and engage consumers
regarding preventive services.
PMID- 29349122
TI - Fast food restaurant locations according to socioeconomic disadvantage, urban
regional locality, and schools within Victoria, Australia.
AB - Features of the built environment provide opportunities to engage in both healthy
and unhealthy behaviours. Access to a high number of fast food restaurants may
encourage greater consumption of fast food products. The distribution of fast
food restaurants at a state-level has not previously been reported in Australia.
Using the location of 537 fast food restaurants from four major chains
(McDonald's, KFC, Hungry Jacks, and Red Rooster), this study examined fast food
restaurant locations across the state of Victoria relative to area-level
disadvantage, urban-regional locality (classified as Major Cities, Inner
Regional, or Outer Regional), and around schools. Findings revealed greater
locational access to fast food restaurants in more socioeconomically
disadvantaged areas (compared to areas with lower levels of disadvantage), nearby
to secondary schools (compared to primary schools), and nearby to primary and
secondary schools within the most disadvantaged areas of the major city region
(compared to primary and secondary schools in areas with lower levels of
disadvantage). Adjusted models showed no significant difference in location
according to urban-regional locality. Knowledge of the distribution of fast food
restaurants in Australia will assist local authorities to target potential policy
mechanisms, such as planning regulations, where they are most needed.
PMID- 29349123
TI - Mortality among white, black, and Hispanic male and female state prisoners, 2001
2009.
AB - Although much research considers the relationship between imprisonment and
mortality, little existing research has tested whether the short-term mortality
advantage enjoyed by prisoners extends to Hispanics. We compared the mortality
rates of non-Hispanic white, non-Hispanic black, and Hispanic male and female
state prisoners to mortality rates in the general population using data from the
Deaths in Custody Reporting Program, the National Prisoner Statistics, the
National Corrections Reporting Program, and the Centers for Disease Control and
Prevention. The results indicate that the mortality advantage for prisoners was
greatest for black males, followed by black females, Hispanic males, white
females, and white males. Hispanic female prisoners were the only group not at a
mortality advantage relative to the general population, with an SMR of 1.18 [95%
CI: 0.93-1.43]. Taken together, the results suggest that future research should
seek to better understand the curious imprisonment-mortality relationship among
Hispanic females, although given the small number of inmate deaths that happen to
this group (~0.6%), this research should not detract from broader research on
imprisonment and mortality.
PMID- 29349124
TI - More than just numbers: Suicide rates and the economic cycle in Portugal (1910
2013).
AB - Suicides are a major concern for public health first and foremost because they
are an avoidable cause of death. Moreover, they can be an indicator of self
reported emotional satisfaction and a good marker of overall well-being. In this
study we examine how different economic and social aspects affected Portuguese
suicide rates for more than one hundred years (1910-2013). We place this exercise
in the specific historical context of the XX and early XXI century in Portugal,
emphasizing the role of economic recessions and expansions. Controlling for
aspects like wars, health care availability, political instability, and
demographic changes, we find a strong association between a decline in the growth
rate of real output and an increase in suicide rates for the whole population. In
this regard, while male suicide rates are non-negligibly influenced by economic
downturns, female suicide rates are in general more responsive to a more open
political and economic environment. Our results are robust if we consider the mid
term cyclical relationship. Our findings advocate that, during recessions, public
health responses should be seen as a crucial component of suicide prevention.
PMID- 29349126
TI - La desesperacion in Latino migrant day laborers and its role in alcohol and
substance-related sexual risk.
AB - The purpose of this study was to better understand the relation between
psychological distress and alcohol and substance related sexual risk in Latino
migrant day laborers (LMDLs). In addition to examining the roles of depression
and anxiety, it was also necessary to examine the role of desesperacion, a
popular Latino idiom of distress frequently expressed by LMDLs in response to the
thwarting of major migration related life goals such as traveling to the U.S. in
search of work to support families, projects and purchases in country of origin.
Given the structural vulnerability of LMDLs to under-employment and frequent
unemployment, LMDLs also refer to desesperacion as a prelude to problem drinking,
substance use, and sexual risk taking. Hence we developed and validated a scale
of desesperacion for LMDLs to explore this culturally relevant construct of
psychological distress in this unique population of Latinos. Based on a cross
sectional survey of 344 LMDLs, this study found that the dissatisfaction subscale
of desesperacion predicted alcohol-related sexual risk taking, while depression
predicted substance-related sexual risk taking. These findings are discussed
including implications of preventing alcohol and substance related sexual risk
taking in LMDLs.
PMID- 29349125
TI - Built environment assessment: Multidisciplinary perspectives.
AB - Context: As obesity has become increasingly widespread, scientists seek better
ways to assess and modify built and social environments to positively impact
health. The applicable methods and concepts draw on multiple disciplines and
require collaboration and cross-learning. This paper describes the results of an
expert team's analysis of how key disciplinary perspectives contribute to
environmental context-based assessment related to obesity, identifies gaps, and
suggests opportunities to encourage effective advances in this arena. Evidence
acquisition: A team of experts representing diverse disciplines convened in 2013
to discuss the contributions of their respective disciplines to assessing built
environments relevant to obesity prevention. The disciplines include urban
planning, public health nutrition, exercise science, physical activity research,
public health and epidemiology, behavioral and social sciences, and economics.
Each expert identified key concepts and measures from their discipline, and
applications to built environment assessment and action. A selective review of
published literature and internet-based information was conducted in 2013 and
2014. Evidence synthesis: The key points that are highlighted in this article
were identified in 2014-2015 through discussion, debate and consensus-building
among the team of experts. Results focus on the various disciplines' perspectives
and tools, recommendations, progress and gaps. Conclusions: There has been
significant progress in collaboration across key disciplines that contribute to
studies of built environments and obesity, but important gaps remain. Using
lessons from interprofessional education and team science, along with
appreciation of and attention to other disciplines' contributions, can promote
more effective cross-disciplinary collaboration in obesity prevention.
PMID- 29349127
TI - Rollout of community-based family health strategy (programa de saude de familia)
is associated with large reductions in neonatal mortality in Sao Paulo, Brazil.
AB - Rationale: Several recent studies suggest that Brazil's Estrategia Saude de
Familia (Family Health Strategy-FHS) has contributed to declines in mortality at
the national and regional level. Comparatively little is known whether this
approach is effective in urban populations with relatively easy access to health
services. Objectives: To use detailed medical data collected as part of Sao
Paulo's Western Region project to examine whether the FHS program had an impact
on child health in Sao Paulo, Brazil. Results: No associations were found between
FHS and birth weight (OR 1.03, 95% CI 0.93-1.29), gestational length (OR 0.98,
95% CI 0.83-1.15) or stillbirth (OR 1.51, 95% CI 0.75-3.03). FHS eligibility was
associated with a 42% reduction in the odds of child mortality (OR 0.58, 95% CI
0.34, 0.91), with largest effect sizes for the early neonatal period (OR 0.18,
95% CI 0.04-0.79). Conclusions: Community based health delivery platforms may be
a highly effective way to reduce neonatal mortality in urban areas of low and
middle income countries, even when access to general health services is almost
universal.
PMID- 29349128
TI - Self-efficacy is associated with increased food security in novel food pantry
program.
AB - We examined the effect of a novel food pantry intervention (Freshplace) that
includes client-choice and motivational interviewing on self-efficacy and food
security in food pantry clients. The study was designed as a randomized control
trial. Participants were recruited over one year from traditional food pantries
in Hartford, CT. Participants were randomized to Freshplace or traditional food
pantries (controls) and data collection occurred at baseline with quarterly
follow-ups for 18 months. Food security was measured using the USDA 18-item Food
Security Module. A newly developed scale was utilized to measure self-efficacy.
Scale reliability was measured using a Cronbach alpha test; validity was measured
via correlating with a related variable. Analyses included chi-square tests for
bivariate analyses and hierarchical linear modeling for longitudinal analyses. A
total of 227 adults were randomized to the Freshplace intervention (n=112) or
control group (n=115). The overall group was 60% female, 73% Black, mean age=51.
The new self-efficacy scale showed good reliability and validity. Self-efficacy
was significantly inversely associated with very low food security (p<.05). Being
in the Freshplace intervention (p=.01) and higher self-efficacy (p=.04) were
independently associated with decreased very low food security. The traditional
food pantry model fails to recognize the influence of self-efficacy on a person's
food security. A food pantry model with client-choice, motivational interviewing
and targeted referral services can increase self-efficacy of clients.
Prioritizing the self-efficacy of clients over the efficiency of pantry
operations is required to increase food security among disadvantaged populations.
PMID- 29349129
TI - Improving but unequal: Temporal trends in Chinese self-rated health, 1990-2012.
AB - This study examines temporal trends in the self-rated health of Chinese adults
from 1990 to 2012. Concentration on this particular period in Chinese history
provides insights into the health implications of China's massive societal
transformation induced by economic reform. A series of cross-classified random
effects models were estimated predicting favorable health status across time
periods and adjusted for age, cohort effect and individual-level covariates.
Results show that more recent birth cohorts exhibit better health conditions than
earlier birth cohorts. However, period effects had a more profound effect than
that of birth cohort. Net of age, cohort and individual-level covariates, there
is a significant and increasing trend in self-rated health since the early 1990s.
The period pattern was non-monotonic, with health improvement in the early 1990s,
a dip later in that decade, but more evidence of improvement by 2012. We also
found that health disparities have widened over the past 20 years, particularly
on the basis of income and educational attainment.
PMID- 29349130
TI - The Hispanic health paradox: New evidence from longitudinal data on second and
third-generation birth outcomes.
AB - This study examines the birth weight of second and third-generation Hispanics
born in California and Florida, two of the major immigrant destination states in
the US. I exploit a unique dataset of linked birth records for two generations of
children born in California and Florida (1970-2009) and linear probability models
to investigate the generational decline in the birth outcomes of Hispanics in the
US. The data allow using an extensive set of socio-demographic controls and
breaking down the results by country of origin. Second-generation children of
Mexican and Cuban origin have better birth outcomes than children of US-born
white women. Children of Puerto Rican origin have instead worse birth outcomes.
The advantage observed among second-generation Hispanics erodes substantially in
the third generation but third-generation Mexicans retain some of it.
PMID- 29349131
TI - Predictors of patient's intentions to participate in pragmatic clinical trials:
An initial exploration.
AB - The Veterans Health Administration is implementing a pragmatic trial research
program, called Point of Care Research (POC-R). The purpose of this telephone
survey in which respondents were randomized to different framing conditions of
the purpose of POC-R was to determine the impact of differing frames of the
purpose of POC-R on attitudes towards the program and intentions to participate;
and the relative importance of different beliefs and attitudes in discriminating
low vs. high intenders to participate in POC-R. The survey addressed veterans'
perceptions and attitudes towards POC-R, and their willingness to participate in
a pragmatic trial. Overall, respondents felt positively towards POC-R and
intended to participate. Differing frames of the purpose of POC-R were not
associated with either attitudes (towards the program) or intentions to
participate. However, specific beliefs and attitudes toward POC-R program were
predictive of intentions to participate.
PMID- 29349132
TI - Why is multiple micronutrient powder ineffective at reducing anaemia among 12-24
month olds in Colombia? Evidence from a randomised controlled trial.
AB - In Colombia's bottom socio-economic strata, 46.6% of children under two are
anaemic. A prevalence of above 20% falls within the WHO guidelines for daily
supplementation with multiple micronutrient powder (MNP). To evaluate the effect
of daily MNP supplementation on anaemia amongst Colombian children aged 12-24
months we ran a cluster RCT (n=1440). In previous work, we found the intervention
had no impact on haemoglobin or anaemia in this population. In this current
paper, we investigate this null result and find it cannot be explained by an
underpowered study design, inaccurate measurements, low adoption of and
compliance with the intervention, or crowding out through dietary substitution.
We conclude that our intervention was ineffective at reducing rates of childhood
anaemia because MNP itself was inefficacious in our population, rather than poor
implementation of or adherence to the planned intervention. Further analysis of
our data and secondary data suggests that the evolution with age of childhood
anaemia in Colombia, and its causes, appear different from those in settings
where MNP has been effective. Firstly, rates of anaemia peak at much earlier ages
and then fall rapidly. Secondly, anaemia that remains after the first year of
life is relatively, and increasingly as children get older, unrelated to iron
deficiency. We suggest that factors during gestation, birth, breastfeeding and
early weaning may be important in explaining very high rates of anaemia in early
infancy. However, the adverse effects of these factors appear to be largely
mitigated by the introduction of solid foods that often include meat. This
renders population wide MNP supplementation, provided after a diet of solid foods
has become established, an ineffective instrument with which to target Colombia's
childhood anaemia problem.
PMID- 29349133
TI - Adverse outcomes in bereaved mothers: The importance of household income and
education.
AB - Intense and enduring psychological distress has been well-documented in numerous
studies on bereaved parents including anxious, depressive, and traumatic stress
symptoms. A state of poverty is also known to increase the risk of psychological
distress in the general population, yet this variable has not yet been
sufficiently evaluated in outcomes specifically for bereaved parents. This study
is the first to investigate poverty, education, and parental bereavement while
examining the relative risk of other variables as informed by the literature. The
findings reveal that poverty was the strongest predictor of psychological
distress when compared to others factors which have traditionally been considered
significant in parental bereavement. Bereaved parents living in poverty may be
less likely to seek support and have fewer available resources. Practice and
policy implications are discussed.
PMID- 29349134
TI - Influence of volunteer-led net step exercise class on older people's self-rated
health in a depopulated town: A longitudinal study.
AB - In a depopulated region where population aging is advancing, it is necessary to
establish a method so local residents themselves can be actively involved in
older people's health promotion. Net Step Exercise, a novel dual-task walking
program, introduced residents to opportunities for physical activities and social
participation without any health specialist support. In one depopulated town
(Ikeda, Nakagawa-gun, Hokkaido, Japan), volunteer residents have held Net Step
Exercise classes throughout the town since 2007. We longitudinally examined the
influence of volunteer-led Net Step Exercise class participation on subsequent
self-rated health in all individuals aged 70-79 years living in Ikeda. A total of
662 people who completed a baseline mail-in questionnaire survey in 2012 were
followed until 2014. Logistic regression analysis was performed to examine the
association with self-rated health after two years of class participation once a
month or more at baseline, after controlling for confounds such as age, sex,
years of education, living alone, baseline self-rated health, regular exercise,
and other physical activities. The odds ratio of poor self-rated health in older
people who participated in classes was 0.53 (95% confidence interval [CI]: 0.34
0.85) compared to older people not participating in classes. Even after
confounding factors were adjusted, the odds ratio of class participation was 0.50
(95% CI: 0.29-0.85). This study showed that participation in volunteer-led Net
Step Exercise might prevent poor self-rated health. Such Net Step Exercise
classes are a feasible method for older people's health promotion in depopulated
municipalities.
PMID- 29349135
TI - A life-course perspective on legal status stratification and health.
AB - Scholars have expressed growing interest in the relationship between legal status
stratification and health. Nevertheless, the extant research often lacks
theoretical underpinnings. We propose the life-course perspective as a
theoretical lens with which to understand relationships between legal status
stratification and health outcomes. In particular, the life-course perspective
guides researchers' attention to historical contexts that have produced
differential social, political, and economic outcomes for immigrants based on
legal status, and to the potentially long-term and intergenerational
relationships between legal status stratification and health. We review four key
dimensions of the life-course perspective and make recommendations for future
directions in public health research on legal status and health.
PMID- 29349137
TI - Premarital childbearing in sub-Saharan Africa: Can investing in women's education
offset disadvantages for children?
AB - Premarital childbearing is common in many parts of sub-Saharan Africa, and may
become increasingly so with the rise in women's age at first marriage. These
trends are concerning given the severe childhood health consequences associated
with being born premaritally. However, women's could condition the experience of
having a premarital birth in a way that lessens its consequences for children.
Extending the large literature on the child health benefits of mothers' education
including her educational attainment and acquisition of key educational skills -
I analyze whether the consequences of being born premaritally are lessened among
children whose mothers are more highly-educated. The study focuses on Malawi, a
southeast African country where child mortality rates remain high. I use
Demographic and Health Survey data to estimate discrete-time logistic regression
models (N=30,411 children younger than age five) of the relationships between
premarital childbearing, mothers' educational background, and child mortality.
The findings confirm that though being born premaritally is associated with
higher child mortality, this is only true for children whose mothers have never
been to school or discontinued at the primary level and/or never learned how to
read. There is no evidence that being born premaritally is associated with
elevated mortality among children whose mothers have been to secondary school
and/or know how to read. The results demonstrate that analyzing how premarital
childbearing intersects with other sources of health inequality enhances our
understanding of the circumstances under which it poses the greatest risk to
child well-being in sub-Saharan Africa.
PMID- 29349136
TI - Breast cancer presentation delays among Arab and national women in the UAE: a
qualitative study.
AB - Breast cancer (BC) is a disease that has improved prospects for survival if
detected and treated early. Delayed help-seeking behavior, with poor survival as
a consequence, is an important public health issue in the Middle East. More than
75% of breast cancer patients in the United Arab Emirates (UAE) seek medical
advice after experiencing a sign or symptom of the disease and many seek such
advice late. Our aim was to explore factors influencing delayed presentation for
treatment after self-discovery of symptoms consistent with breast cancer in Arab
women in the United Arab Emirates (UAE), and to explore facilitators and barriers
of women's health seeking behavior in the complex religiously dominated society
of the UAE. A qualitative descriptive approach using semi-structured interviews
was used. We interviewed nineteen BC survivors aged 35-70 who have experienced
delayed presentation to treatment after symptomatic recognition of BC. The time
interval between initial experience of symptoms consistent with BC, and taking
action to seek medical help was between three months to three years. The key
themes that emerged from the interviews were varying responses to symptom
recognition, fear of societal stigmatization, and concerns regarding abandonment
by spouse because of BC. Culture has a strong influence on the decisions of women
in the UAE society. The lack of awareness about signs and symptoms of BC and
routine screening has an important effect on symptom appraisal and subsequently
decision making regarding options for treatment.
PMID- 29349138
TI - Psychosocial job quality in a national sample of working Australians: A
comparison of persons working with versus without disability.
AB - Objectives: There is growing international policy interest in disability
employment, yet there has been little investigation of job quality among people
working with disability. This study uses Australian national data to compare the
psychosocial job quality of people working with versus without disability.
Methods: We used 10 annual waves of data from a large representative Australian
panel survey to estimate the proportion of the population experiencing poorer
psychosocial job quality (overall and by individual 'adversities' of low job
control, high demands, high insecurity, and low fairness of pay) by disability
status and impairment type. We used logistic regression to examine the pooled
cross-sectional associations between disability and job quality, adjusting for
age, sex, education and job type. Results: Those working with any disability
showed approximately 25% higher odds of reporting one or more adversity at work
(OR: 1.23, 95% CI: 1.15, 1.31), and this finding was consistent across impairment
types with the exception of intellectual/developmental disability. Estimates were
largely unchanged after adjustments. Similar results were found for reporting two
or more adversities compared one or more. Conclusions: We observed that working
people with a disability in Australia reported systematically poorer psychosocial
job quality than those working without disability. These results suggest the need
for further research to understand the reasons for these patterns, as well as
policy and practice efforts to address this inequity.
PMID- 29349140
TI - Working out what works: The case of midwife led care - Commentary on: Is model of
care associated with infant birth outcomes among vulnerable women? A scoping
review of midwifery-led versus physician-led care.
PMID- 29349139
TI - Is model of care associated with infant birth outcomes among vulnerable women? A
scoping review of midwifery-led versus physician-led care.
AB - This scoping review investigates if, over the last 25 years in high resource
countries, midwives' patients of low socioeconomic position (SEP) were at more or
less risk of adverse infant birth outcomes compared to physicians' patients.
Reviewers identified 917 records in a search of 12 databases, grey literature,
and citation lists. Thirty-one full documents were assessed and nine studies met
inclusion criteria. Eight studies were assessed as moderate in quality; one study
was given a weak rating. Of the moderate quality studies, the majority found no
statistical difference in outcomes according to model of care for preterm birth,
low or very low birth weight, or NICU admission. No study reported a
statistically significant difference for small for gestational age birth (2
studies), or mean or low Apgar score (4 studies). However, one study found a
reduced risk of preterm birth (AOR=0.70, p<0.01), and heavier mean infant birth
weight (3325 g vs. 3282 g, p<0.01) for midwifery patients. Another study reported
lower risk of low (RR=0.59, 95% CI: 0.46, 0.73) and very low birthweight
(RR=0.44, 95% CI: 0.23, 0.85) for midwifery care. And, a third study reported a
decrease in stays (1-3 days) in NICU (Adjusted Risk Difference=-1.8, 95% CI:
3.9, 0.2) for midwifery patients, though no overall difference in NICU admission
of any duration. Other studies reported significant differences favoring
midwifery care for mean birth weight (3598 g vs. 3407.3 g, p<0.05; 3233 g vs.
3089 g, p<0.05; 2 studies) and very low birth weight (OR=0.35, 95% CI:0.1, 0.9),
for sub-groups within the larger study populations. This scoping review
documented heterogeneity in study designs and analytical methods, inconsistent
findings, moderate methodological quality, and lack of currency. There is a need
for new studies to definitively establish if and how a midwifery-led model of
care influences birth outcomes for women of low SEP.
PMID- 29349141
TI - Intraclass correlation values for adolescent health outcomes in secondary schools
in 21 European countries.
AB - Background: Cluster randomised controlled trials (CRCTs) are increasingly used to
evaluate the effectiveness of interventions for improving health. A key feature
of CRCTs is that individuals in clusters are often more alike than individuals in
different clusters, irrespective of treatment. This similarity within clusters
needs to be taken into account when planning CRCTs to obtain adequate sample
sizes, and when analysing clustered data to obtain correct estimates. Methods:
Nationally representative data from 15 to 16 year olds were analysed, from 21 of
the 35 countries that participated in the 2007 European School Survey Project on
Alcohol and Other Drugs. Within country school level intra-class correlation
coefficients (ICCs) were calculated for substance use (self-reported alcohol use,
regular alcohol use, binge drinking, any smoking, regular smoking, and illicit
drug use) and psychosocial health (depressive mood and self-esteem). Unadjusted
and adjusted ICCs are presented. ICCs are adjusted for student sex and
socioeconomic status. Results: ICCs ranged from 0.01 to 0.21, with the highest
(0.21) reported for regular smoking. Within country school level ICCs varied
substantially across health outcomes, and among countries for the same health
outcomes. Estimated ICCs were consistently higher for substance use (range 0.01
0.21), than for psychosocial health (range 0.01-0.07). Within country ICCs for
health outcomes varied by changes in the measurement of particular health
outcomes, for example the ICCs for regular smoking (range 0.06-0.21) were higher
than those for having smoked at all in the last month (range 0.03-0.17).
Conclusions: For school level ICCs to be effectively utilised in informing sample
size requirements for CRCTs and adjusting estimates from meta-analyses, the
school level ICCs need to be both country and outcome specific.
PMID- 29349142
TI - Towards an understanding of the structural determinants of oral health
inequalities: A comparative analysis between Canada and the United States.
AB - Objective: To compare the magnitude of, and contributors to, income-related
inequalities in oral health outcomes within and between Canada and the United
States over time. Methods: The concentration index was used to estimate income
related inequalities in three oral health outcomes from the Nutrition Canada
National Survey 1970-1972, Canadian Health Measures Survey 2007-2009, Health and
Nutrition Examination Survey I 1971-1974, and National Health and Nutrition
Examination Survey 2007-2008. Concentration indices were decomposed to determine
the contribution of demographic and socioeconomic factors to oral health
inequalities. Results: Our estimates show that over time in both countries,
inequalities in decayed teeth and edentulism were concentrated among the poor and
inequalities in filled teeth were concentrated among the rich. Over time,
inequalities in decayed teeth increased and decreased for measures of filled
teeth and edentulism in both countries. Inequalities were higher in the United
States compared to Canada for filled and decayed teeth outcomes. Socioeconomic
characteristics (education, income) contributed greater to inequalities than
demographic characteristics (age, sex). As well, income contributed more to
inequalities in recent surveys in both Canada and the United States. Conclusions:
Inequalities in oral health have persisted over the past 35 years in Canada and
the United States, and are associated with age, sex, education, and income and
have varied over time.
PMID- 29349143
TI - Changes in visitor profiles and activity patterns following dog supportive
modifications to parks: A natural experiment on the health impact of an urban
policy.
AB - Urban parks are important settings for physical activity, but few natural
experiments have investigated the influences of park modifications on activity
patterns and visitor profiles.We assessed the impact of implementing a municipal
policy on off-leash dogs in city parks in Calgary (Alberta, Canada). Systematic
observation undertaken in 2011 and 2012 within four parks captured patterns of
use, activities, and visitors' characteristics. After baseline data collection,
off-leash areas were created in two parks only. We compared changes in the
sociodemographic and activity profiles in all parks between 2011 and 2012.
Visitors with dogs participated in less intense activity relative to visitors
without dogs. In both modified parks, the intensity of children's activities
decreased, while the intensity of adults' activities remained stable. Adjusting
for visitor characteristics, the likelihood of dog-related visits, relative to
other activities, significantly decreased in one of the two modified parks (odds
ratio 0.55, p<.05). Accommodating off-leash dogs in parks has the potential to
modify activities undertaken inside parks as well as the profile of visitors, but
may not increase park visits among dog-walkers in the short term. Recreation,
park, and urban planners and policy-makers need to consider the needs and
preferences of the broader community in the design and redesign of public parks.
PMID- 29349144
TI - Food and housing insecurity and health status among U.S. adults with and without
prior military service.
AB - Food and housing insecurity may contribute to poorer mental and physical health.
It is unclear as to whether those with prior military service, compared to those
without, are more vulnerable to these current stressors. The objective of this
study was to use U.S. population-based data to determine whether prior military
service moderates the association of food and housing insecurity with poor mental
and physical health. We analyzed data from nine states administering the Social
Context module from the 2011 and 2012 Behavioral Risk Factor Surveillance System.
Multivariable logistic regression was used to examine the associations of housing
and food insecurity with poor mental and physical health and potential
modification by military service. Compared with those with a history of military
service, those without had higher prevalence of food insecurity (23.1% versus
13.7%) and housing insecurity (36.0% versus 22.5%). Food insecurity was
associated with poor mental and physical health (mental health: odds ratio
(OR)=3.47, 95% confidence interval (CI)=[3.18-3.77]; physical health: OR=3.21,
95% CI=[2.92-3.53]). Similar associations were observed between housing
insecurity and poor mental and physical health. Prior military service was
significantly associated with poor physical health. Interaction terms of prior
military service with food and housing were not statistically significant. Food
and housing insecurity does not appear to differentially impact mental and
physical health among those with and without military service.
PMID- 29349145
TI - Residential environments, alcohol advertising, and initiation and continuation of
alcohol consumption among adolescents in urban Taiwan: A prospective multilevel
study.
AB - Background: Research indicates that place characteristics and the media
environment are important contextual determinants of underage drinking behaviors
in Western countries, but it is unknown whether these exposures influence
adolescent alcohol consumption outside Western contexts, including in Asia's
emerging global alcohol markets. Guided by the social ecological framework, we
prospectively investigated the influences of place characteristics and alcohol
advertising on initiation and continuation of alcohol consumption among
adolescents in Taipei, Taiwan. Methods: Data on individual-level characteristics,
including alcohol use behaviors and perceived exposure to alcohol advertising,
were obtained from two waves of a longitudinal school-based study through a
stratified probability sampling method in 2010 (Grade 7/Grade 8, aged 13-14 years
old) and 2011-2012 (Grade 9, aged 15 years old) from 1795 adolescents residing in
22 of 41 districts in Taipei. Data on district-level characteristics were drawn
from administrative sources and Google Street View virtual audit to describe
districts where adolescents lived at baseline. Hierarchical generalized linear
models tested hypotheses about the associations of place characteristics and
perceived alcohol advertising with underage drinking, with stratification by
baseline lifetime alcohol consumption. Results: Among alcohol-naive adolescents,
lower district-level economic disadvantage, a higher proportion of betel nut
kiosks (a relatively unregulated alcohol source) compared to off-premises alcohol
outlets, and exposure to television-based alcohol advertising predicted increased
likelihood of alcohol initiation at one-year follow-up. Among alcohol-experienced
adolescents, greater spatial access to off-premises alcohol outlets, and lower
access to metro rapid transportation (MRT) and to temples were found to predict a
subsequent increased likelihood of continued alcohol use. Parental drinking
moderated the relationship between district-level violent crime and initiation of
alcohol consumption. Conclusions: These findings suggest that local social
economic status, alcohol access, and institutional resource and individual media
exposure affect underage drinking behaviors in Taiwan. We discuss potential
public health implications for place-based interventions. Future research on
place, media, and adolescent alcohol consumption in Asian contexts is warranted.
PMID- 29349146
TI - Inpatient migration patterns in persons with spinal cord injury: A registry study
with hospital discharge data.
AB - This study investigated and compared patient migration patterns of persons with
spinal cord injury, the general population and persons with morbid obesity,
rheumatic conditions and bowel disease, for secondary health conditions, across
administrative boundaries in Switzerland. The effects of patient characteristics
and health conditions on visiting hospitals outside the residential canton were
examined using complete, nationwide, inpatient health records for the years 2010
and 2011. Patients with spinal cord injury were more likely to obtain treatment
outside their residential canton as compared to all other conditions.
Facilitators of patient migration in persons with spinal cord injury and the
general hospital population were private or accidental health insurances covering
costs. Barriers of patient migration in persons with spinal cord injury were old
age, severe multimorbidity, financial coverage by basic health insurance, and
minority language region.
PMID- 29349148
TI - Assessing adolescent spiritual health and well-being (commentary related to
Social Science & Medicine - Population Health, ref: SSMPH-D-15-00089).
PMID- 29349147
TI - Developmental patterns of adolescent spiritual health in six countries.
AB - The spiritual health of adolescents is a topic of emerging contemporary
importance. Limited numbers of international studies provide evidence about
developmental patterns of this aspect of health during the adolescent years.
Using multidimensional indicators of spiritual health that have been adapted for
use within younger adolescent populations, we therefore: (1) describe aspects of
the perceptions of the importance of spiritual health of adolescents by
developmental stage and within genders; (2) conduct similar analyses across
measures related to specific domains of adolescent spiritual health; (3) relate
perceptions of spiritual health to self-perceived personal health status. Cross
sectional surveys were administered to adolescent populations in school settings
during 2013-2014. Participants (n=45,967) included eligible and consenting
students aged 11-15 years in sampled schools from six European and North American
countries. Our primary measures of spiritual health consisted of eight questions
in four domains (perceived importance of connections to: self, others, nature,
and the transcendent). Socio-demographic factors included age, gender, and
country of origin. Self-perceived personal health status was assessed using a
simple composite measure. Self-rated importance of spiritual health, both overall
and within most questions and domains, declined as young people aged. This
declining pattern persisted for both genders and in all countries, and was most
notable for the domains of "connections with nature" and "connections with the
transcendent". Girls consistently rated their perceptions of the importance of
spiritual health higher than boys. Spiritual health and its domains related
strongly and consistently with self-perceived personal health status. While
limited by the 8-item measure of perceived spiritual health employed, study
findings confirm developmental theories proposed from qualitative observation,
provide foundational evidence for the planning and targeting of interventions
centered on adolescent spiritual health practices, and direction for the study of
spiritual health in a general population health survey context.
PMID- 29349149
TI - The relationship between relative deprivation and self-rated health among
Palestinian women in refugee camps in Lebanon.
AB - Background: Relative deprivation (RD) has been advanced as a theory to explain
the relationship between income inequality and health in high-income countries.
In this study, we tested the theory in a low-income protracted refugee setting in
a middle-income country. Methods: Using data from the 2010 Socioeconomic Survey
of Palestine Refugees in Lebanon, we examined the relationship between RD and
health among a representative sample of Palestinian refugee women (N=1047). Data
were gathered utilizing a household questionnaire with information on socio
demographics and an individual-level questionnaire with information on the health
of each respondent. We examined self-rated health (SRH) as the main health
measure but also checked the sensitivity of our results using self-reported
chronic conditions. We used two measures for absolute SES: total household
monthly expenditures on non-food goods and services and total household monthly
expenditures on non-health goods and services. With refugee camp as a reference
group, we measured a household's RD as a household's rank of absolute SES within
the reference group, multiplied by the distance between its absolute SES and the
average absolute SES of all households ranked above it. We investigated the
robustness of the RD-SRH relationship using these two alternative measures of
absolute SES. Results: Our findings show that, controlling for absolute SES and
other possible confounders, women report significantly poorer health when they
live in households with a higher score on our RD measure (because of either lower
relative rank or lower relative SES compared to households better off in the
reference group which we take to be the refugee camp). While RD is always
significant as a determinant of SRH under a variety of specifications, absolute
SES is not consistently significant. These findings persist when we use self
reported chronic conditions as our measure of health instead of SRH, suggesting
that the relationship between health and RD may be operating through a
psychosocial mechanism. Discussion: Our findings underscore the importance of
examining RD under conditions of poverty and in diverse socio-cultural contexts.
They also highlight that public health approaches should be concerned with
reducing social inequalities in low-income settings in addition to alleviating
poverty.
PMID- 29349150
TI - Paradox and privilege: A 55-year follow-up of the mortality of Yale College
graduates.
AB - Objective: Two hypotheses were tested: 1. People from privileged backgrounds had
better survival than those from less privileged backgrounds. 2. The advantages of
privilege were vitiated by fraternity membership. Methods: A 55-year
retrospective cohort study of survival since 1960 of 945 graduates of Yale
College followed to 2015. Results: The survival of graduates of private secondary
schools (the privileged group) did not differ from that of public school
graduates. However, graduates of private secondary schools who had not joined a
fraternity in college had significantly better survival than private school
graduates who had joined fraternities and than public school graduates, whether
fraternity members or not. Conclusions: The benefits of a privileged background
in respect of survival were undermined by fraternity membership. It is suggested
that both self-selection and substance mis-use may have contributed to the
survival difference.
PMID- 29349151
TI - Can socioeconomic factors explain geographic variation in overweight in Norway?
AB - We explore if the geographic variation in excess body-mass in Norway can be
explained by socioeconomic status, as this has consequences for public policy.
The analysis was based on individual height and weight for 198,311 Norwegian
youth in 2011, 2012 and 2013, stemming from a compulsory screening for military
service, which covers the whole population aged seventeen. These data were merged
with municipality-level socioeconomic status (SES) variables and we estimated
both ecological models and two-level models with a random term at the
municipality level. Overweight was negatively associated with income, education
and occupation at municipality level. Furthermore, the municipality-level
variance in overweight was reduced by 57% in females and 40% in males, when SES
factors were taken into account. This suggests that successful interventions
aimed at reducing socioeconomic variation in overweight will also contribute to
reducing the geographic variation in overweight, especially in females.
PMID- 29349152
TI - Cross-border ties and the reproductive health of India's internal migrant women.
AB - The literature on how social ties influence sexual and reproductive health is
well established; however, one significant limitation of this research is the
influence of social ties to hometowns among migrant women. Drawing from cross
border social ties literature, the objective of this study is to assess how cross
border social ties influence use of family planning and institutional deliveries
among internal migrant women in India. Cross-sectional data come from 711 migrant
women living in slums in Uttar Pradesh, India. Multivariable logistic regression
was used to assess odds of modern use of family planning and odds of
institutional deliveries with cross-border tie indicators. Results suggest that
higher cross-border ties were associated with 2.35 times higher odds of family
planning use (p<0.1) and 2.73 times higher odds of institutional delivery
(p<0.05). This study suggests that social ties to hometowns may serve as a
protective factor, possibly through increased social support, to migrants in
regards to reproductive decision-making and use of reproductive health services.
Future studies should explore potential mechanisms for these findings.
PMID- 29349153
TI - Inequalities in mental health and well-being in a time of austerity: Baseline
findings from the Stockton-on-Tees cohort study.
AB - Since 2010, the UK has pursued a policy of austerity characterised by public
spending cuts and welfare changes. There has been speculation - but little actual
research - about the effects of this policy on health inequalities. This paper
reports on a case study of local health inequalities in the local authority of
Stockton-on-Tees in the North East of England, an area characterised by high
spatial and socio-economic inequalities. The paper presents baseline findings
from a prospective cohort study of inequalities in mental health and mental
wellbeing between the most and least deprived areas of Stockton-on-Tees. This is
the first quantitative study to explore local mental health inequalities during
the current period of austerity and the first UK study to empirically examine the
relative contributions of material, psychosocial and behavioural determinants in
explaining the gap. Using a stratified random sampling technique, the data was
analysed using multi-level models that explore the gap in mental health and
wellbeing between people from the most and least deprived areas of the local
authority, and the relative contributions of material, psychosocial and
behavioural factors to this gap. The main findings indicate that there is a
significant gap in mental health between the two areas, and that material and
psychosocial factors appear to underpin this gap. The findings are discussed in
relation to the context of the continuing programme of welfare changes and public
spending cuts in the UK.
PMID- 29349154
TI - Spirituality, religiosity, aging and health in global perspective: A review.
AB - Persistent population aging worldwide is focusing attention on modifiable factors
that can improve later life health. There is evidence that religiosity and
spirituality are among such factors. Older people tend to have high rates of
involvement in religious and/or spiritual endeavors and it is possible that
population aging will be associated with increasing prevalence of religious and
spiritual activity worldwide. Despite increasing research on religiosity,
spirituality and health among older persons, population aging worldwide suggests
the need for a globally integrated approach. As a step toward this, we review a
subset of the literature on the impact of religiosity and spirituality on health
in later life. We find that much of this has looked at the relationship between
religiosity/spirituality and longevity as well as physical and mental health.
Mechanisms include social support, health behaviors, stress and psychosocial
factors. We identify a number of gaps in current knowledge. Many previous studies
have taken place in the U.S. and Europe. Much data is cross-sectional, limiting
ability to make causal inference. Religiosity and spirituality can be difficult
to define and distinguish and the two concepts are often considered together,
though on balance religiosity has received more attention than spirituality. The
latter may however be equally important. Although there is evidence that
religiosity is associated with longer life and better physical and mental health,
these outcomes have been investigated separately rather than together such as in
measures of health expectancy. In conclusion, there is a need for a unified and
nuanced approach to understanding how religiosity and spirituality impact on
health and longevity within a context of global aging, in particular whether they
result in longer healthy life rather than just longer life.
PMID- 29349155
TI - Impact of falling on social participation and social support trajectories in a
middle-aged and elderly European sample.
AB - Whereas falls are frequent and traumatic events for the elderly, their long-term
consequences in terms of the social lives of older fallers are understudied. This
study aimed to identify the impact of falling on the trajectories of social
participation and social support of older people in Europe. Our sample consisted
of 16,583 people aged 50-95 years from 10 European countries who responded to the
waves 1, 2 and 4 of the Survey of Health Ageing and Retirement in Europe. The
impact of falling on the trajectories of social participation and social support
was examined using generalised estimating equation (GEE) models. The effect of
the interactions between falling and frailty and between falling and social
support on social participation was assessed. Falls were negatively associated
with social participation (OR=0.73, p<0.001) and positively associated with
social support (OR=2.20, p<0.001). For social participation, this effect was
moderated by frailty; the interaction term between frailty and fall highlighted
the finding that frailty better explained the global trajectory of social
participation compared with falling. Social support did not buffer the negative
impact of falling on social participation. Falls can be considered stressful
events that have implications beyond the health context. Frail people who have
fallen should be targeted in prevention and rehabilitation programmes; specific
attention should also be paid to the relatives of fallers, who appeared to be
more intensively solicited after a fall.
PMID- 29349156
TI - Association of partner, parental, and employment statuses with self-rated health
among German women and men.
AB - The association of partner, parental, and employment statuses with health is
usually discussed in terms of either the multiple role burden hypothesis or the
multiple role attachment hypothesis. The first hypothesis states that combining
work and family roles increases the burden of responsibility, which in turn
increases the pressure and stress associated with competing roles, leading to
poorer health. The multiple role attachment hypothesis argues that multiple
responsibilities provide attachment to broader networks, which then provide
social support and resources that enhance health. We analyzed pooled data from
the German Health Update carried out by the Robert Koch Institute in 2009, 2010,
and 2012. The data were collected by computer-assisted telephone interviews. The
sample comprised 28,086 people aged 30-54 years. The data were assessed with
logistic regression analysis and interaction models. The gender-differentiated
analysis of partnership, parenthood, and employment, after adjusting for social
and demographic characteristics, revealed small interaction effects among all
three social roles with self-rated health in women and men. Non-employment showed
the strongest relationship with poor self-rated health. It was significantly
associated with lower self-rated health in both men and women in most of the
family arrangements. These associations were higher in men than in women.
Furthermore, in all family arrangements, female part-time employees were as
healthy as female fulltime employees. A more subtle association was found in men:
the odds of reporting poorer self-rated health were greater among non-parents
employed part time than among those employed full time, but lower than among
those who were non-employed. Among fathers, part-time employees did not have
statistically better health than full-time employees.The findings support
somewhat the multiple role attachment hypothesis, rather than the multiple role
burden hypothesis. Because employment has great importance for both women's and
men's health, the compatibility of work and family roles should be improved.
PMID- 29349157
TI - Political fragmentation and widening disparities in African-American and white
mortality, 1972-1988.
AB - Objective: During the 1970s and 1980s in the U.S., population movement, urban
sprawl and urban governance reform led to a proliferation of local, autonomous
jurisdictions. Prior literature examines how this creation of local governments,
also referred to as political fragmentation, contributes to economic growth and
social inequality. We examine the impact of political fragmentation on health
equity by testing the hypothesis that the mortality disparity between whites and
African-Americans varies positively with political fragmentation. Methods: We
retrieved mortality data from the multiple cause-of-death file and calculated
total number of local governments per 1000 residents in a county to measure the
degree of political fragmentation. We focused on 226 U.S. counties with
population size greater than 200,000 and restricted the analysis to four distinct
periods with overlapping government and mortality data (1972-73, 1977-78, 1982
83, and 1987-88). We applied generalized estimating equation methods that permit
analysis of clustered data over time. Methods also controlled for the age
structure of the population, reductions in mortality over time, and confounding
by county-level sociodemographic variables. Results: Adjusted coefficients of
fragmentation are positive and statistically significant for both whites (coef:
2.60, SE: 0.60, p<0.001) and African-Americans (coef: 5.31, SE: 1.56, p<0.001).
The two-fold larger positive coefficient for African-Americans than for whites
indicates a greater racial disparity in mortality among more politically
fragmented urban counties and/or time periods. Conclusions: From 1972 to 1988,
political fragmentation in large urban counties moves positively with the
racial/ethnic gap in mortality between whites and African-Americans. We discuss
intervening mechanisms through which political fragmentation may
disproportionately affect mortality among African-Americans.
PMID- 29349158
TI - Financial hardship, mastery and social support: Explaining poor mental health
amongst the inadequately employed using data from the HILDA survey.
AB - Objective: This study analysed data from the Household Income and Labour Dynamics
in Australia (HILDA) Survey to examine the relationship between employment status
and mental health, and the mediating effects of financial hardship, mastery and
social support. In addition, the study sought to explore the effects of duration
of unemployment on mental health. Methods: The primary analysis used three waves
of data from the HILDA Survey with 4965 young adult respondents. Longitudinal
population-averaged logistic regression models assessed the association of
employment status and mental health, including the contribution of mastery,
financial hardship and social support in explaining this association between
employment groups (unemployed vs. employed; under employed vs. employed).
Sensitivity analyses utilised a fixed-effects approach and also considered the
full-range of working-age respondents. Regression analysis was used to explore
the effect of duration of unemployment on mental health. Results: Respondents'
who identified as unemployed or underemployed were at higher risk of poor mental
health outcomes when compared to their employed counterparts. This association
was ameliorated when accounting for mastery, financial hardship and social
support for the unemployed, and was fully mediated for the underemployed. The
fixed-effects models showed the transition to unemployment was associated with a
decline in mental health and that mastery in particular contributed to that
change. The same results were found with a broader age range of respondents.
Finally, the relationship between duration of unemployment and mental health was
not linear, with mental health showing marked decline across the first 9 weeks of
unemployment. Conclusions and implications: Mastery, social support and financial
hardship are important factors in understanding the association of poor mental
health with both unemployment and underemployment. Furthermore, the results
suggest that the most deleterious effects on mental health may occur in the first
two months of unemployment before plateauing. In order to prevent deterioration
in mental health, these findings suggest intervention should commence immediately
following job loss.
PMID- 29349159
TI - HIV in Japan: Epidemiologic puzzles and ethnographic explanations.
AB - Japan is widely perceived to have a low level of HIV occurrence; however, its HIV
epidemics also have been the subject of considerable misunderstanding globally. I
used a ground truthing conceptual framework to meet two aims: first, to determine
how accurately official surveillance data represented Japan's two largest
epidemics (urban Kansai and Tokyo) as understood and experienced on the ground;
and second, to identify explanations for why the HIV epidemics were unfolding as
officially reported. I used primarily ethnographic methods while drawing upon
epidemiology, and compared government surveillance data to observations at
community and institutional sites (459 pages of field notes; 175 persons
observed), qualitative interviews with stakeholders in local HIV epidemics (n =
32), and document research (n = 116). This revealed seven epidemiologic puzzles
involving officially reported trends and conspicuously missing information.
Ethnographically grounded explanations are presented for each. These included
factors driving the epidemics, which ranged from waning government and public
attention to HIV, to gaps in sex education and disruptive leadership changes in
public institutions approximately every two years. Factors constraining the
epidemics also contributed to explanations. These ranged from subsidized medical
treatment for most people living with HIV, to strong partnerships between
government and a well-developed, non-governmental sector of HIV interventionists,
and protective norms and built environments in the sex industry. Local and
regional HIV epidemics were experienced and understood as worse than government
reports indicated, and ground-level data often contradicted official knowledge.
Results thus call into question epidemiologic trends, including recent
stabilization of the national epidemic, and suggest the need for revisions to the
surveillance system and strategies that address factors driving and constraining
the epidemics. Based upon its utility in the current study, ground truthing has
value as a conceptual framework for research and shows promise for future
theoretical development.
PMID- 29349160
TI - Theoretical basis and explanation for the relationship between area-level social
inequalities and population oral health outcomes - A scoping review.
AB - This study was conducted to review the evidence on the association between area
level social inequalities and population oral health according to type and extent
of social theories. A scoping review was conducted of studies, which assessed the
association between area-level social inequality measures, and population oral
health outcomes including self-rated oral health, number of teeth, dental caries,
periodontal disease, tooth loss, oral health-related quality of life (OHRQoL) and
dental pain. A search strategy was applied to identify evidence on PubMed,
MEDLINE (Ovid), EMBASE, Web of Science, ERIC, Sociological Abstracts, Social
Services Abstracts, references of selected studies, and further grey literature.
A qualitative content analysis of the selected studies was conducted to identify
theories and categorize studies according to their theoretical basis. A total of
2892 studies were identified with 16 included in the review. Seven types of
social theories were used on 48 occasions within the selected studies including:
psychosocial (n=13), behavioural (n=10), neo-material (n=10), social capital
(n=6), social cohesion (n=4), material (n=3) and social support (n=2). Of the
selected studies, four explicitly tested social theories as pathways from
inequalities to population oral health outcomes, three used a theoretical
construct, seven used theories for post-hoc explanation and two did not have any
use of theory. In conclusion, psychosocial theories were used most frequently.
Although theories were often mentioned, majority of these studies did not test a
social theory.
PMID- 29349161
TI - Does multilingualism affect the incidence of Alzheimer's disease?: A worldwide
analysis by country.
AB - It has been suggested that the cognitive requirements associated with bi- and
multilingual processing provide a form of mental exercise that, through increases
in cognitive reserve and brain fitness, may delay the symptoms of cognitive
failure associated with Alzheimer's disease and other forms of dementia. We
collected data on a country-by-country basis that might shed light on this
suggestion. Using the best available evidence we could find, the somewhat mixed
results we obtained provide tentative support for the protective benefits of
multilingualism against cognitive decline. But more importantly, this study
exposes a critical issue, which is the need for more comprehensive and more
appropriate data on the subject.
PMID- 29349162
TI - Neighbourhood social and built environment factors and falls in community
dwelling canadian older adults: A validation study and exploration of structural
confounding.
AB - Older persons are vulnerable to the ill effects of their social and built
environment due to age-related limitations in mobility and bio-psychological
vulnerability. Falls are common in older adults and result from complex
interactions between individual, social, and contextual determinants. We
addressed two methodological issues of neighbourhood-health and social
epidemiological studies in this analysis: (1) validity of measures of
neighbourhood contexts, and (2) structural confounding resulting from social
sorting mechanisms. Baseline data from International Mobility in Aging Study were
used. Samples included community-dwelling Canadians older than 65 living in
Kingston (Ontario) and St-Hyacinthe (Quebec). We performed factor analysis and
ecometric analysis to assess the validity of measures of neighbourhood social
capital, socioeconomic status, and the built environment and stratified tabular
analyses to explore structural confounding. The scales all demonstrated good
psychometric and ecometric properties. There was an evidence of the existence of
structural confounding in this sample of Canadian older adults as some
combinations of strata for the three neighbourhood measures had no population.
This limits causal inference in studying relationships between neighbourhood
factors and falls and should be taken into account in aetiological aging
research.
PMID- 29349163
TI - Making health information meaningful: Children's health literacy practices.
AB - Children's health and wellbeing is high on the research and policy agenda of many
nations. There is a wealth of epidemiological research linking childhood
circumstances and health practices with adult health. However, echoing a broader
picture within child health research where children have typically been viewed as
objects rather than subjects of enquiry, we know very little of how, in their
everyday lives, children make sense of health-relevant information. This paper
reports key findings from a qualitative study exploring how children understand
food in everyday life and their ideas about the relationship between food and
health. 53 children aged 9-10, attending two socio-economically contrasting
schools in Northern England, participated during 2010 and 2011. Data were
generated in schools through interviews and debates in small friendship groups
and in the home through individual interviews. Data were analysed thematically
using cross-sectional, categorical indexing. Moving beyond a focus on what
children know the paper mobilises the concept of health literacy (Nutbeam, 2000),
explored very little in relation to children, to conceptualise how children
actively construct meaning from health information through their own embodied
experiences. It draws on insights from the Social Studies of Childhood (James and
Prout, 2015), which emphasise children's active participation in their everyday
lives as well as New Literacy Studies (Pahl and Rowsell, 2012), which focus on
literacy as a social practice. Recognising children as active health literacy
practitioners has important implications for policy and practice geared towards
improving child health.
PMID- 29349164
TI - The 2005 London terror attacks: An investigation of changes in psychological
wellbeing and social capital pre- and post-attacks (2003-07)-A UK panel study.
AB - The London public transport suicide bombings, which occurred on 7th July 2005,
were described as the worst single terrorist atrocity on British soil to date.
Past acts of terrorism have been associated with deterioration in population
mental health. They may also negatively impact levels of social capital, which is
considered a buffer against poor mental health outcomes. By employing panel data
from the British Household Panel Survey and following the same individuals
(NT=9287) three times over a five-year period (2003, 2005 and 2007), the aim of
this longitudinal multilevel study was to investigate: (i) the impact of
terrorism on individual-level social capital (generalised trust and social
participation) across the UK; and (ii) the buffering effects of social capital on
psychological wellbeing (GHQ-12). By comparing 2005 and 2007 covariate values
(including the two social capital proxies) against their pre-terror baseline
(2003) measurements in two separate multilevel logistic regression models, we
examined the immediate and longer-term effects of the 2005 attacks on our GHQ-12
outcome. Compared to baseline, generalised trust dropped from 44% to 36%
immediately post-terror attacks in 2005, while local participation increased from
45.8% to 47.5%. Social capital levels started to return to baseline levels by
2007, yet both proxies maintained independent buffering effects against poor GHQ
12 scores in years 2005 and 2007. From this empirical evidence, it seems that
though generalised trust levels are negatively affected by acts of terrorism, the
accompanying increase in local active participation may aid in the re
establishment of societal norms and beliefs in later years. Decision makers
should be aware that such atrocities may negatively impact on populations'
generalised trust in the shorter-term. To safeguard against losing this buffer
against poor mental health outcomes, local active participation should be
encouraged.
PMID- 29349165
TI - Trajectories of informal care and health.
AB - The evidence of the impact of informal care provision on the health of carers
presents a complex and contested picture, depending on the characteristics of the
care studied, including its duration, which has been relatively short in previous
research (up to 4 years). Drawing on data from the Office for National Statistics
Longitudinal Study, a 1% sample of linked Census records for respondents in
England and Wales (N=270,054), this paper contributes original insights on the
impact of care provision on the carer's health ten years later. The paper
explores differentials in self-reported health in 2011 between individuals
according to their caring status at 2001 and 2011, and controlling for a range of
demographic and socio-economic characteristics. The results show that individuals
providing informal care in 2011 (regardless of carer status in 2001) exhibit
lower odds of poor health in 2011 than those who did not provide care in both
2001 and 2011. Taking the intensity of care into account, 'heavy' carers in 2001
(i.e. caring for more than 20 h per week) who were not caring in 2011 show a
higher likelihood of reporting poor health than non-carers, while those who were
'heavy' carers in both 2001 and 2011 are around one-third less likely to report
poor health at 2011 compared to non-carers (2001 and 2011). These findings
provide new insights in relation to repeat caring and its association with the
carer's health status, further contributing to our understanding of the complex
relationship between informal care provision and the carer's health.
PMID- 29349166
TI - The impacts of public mammography screening on the relationship between
socioeconomic status and cancer stage.
AB - This study aimed to investigate the relationship between socioeconomic inequality
and mortality following the introduction of a public mammography screening
program in Norway by exploring the role of change in stage distribution as the
mechanism for differences before and after the introduction of the screening
program. Attained education level was used as a measure of socioeconomic status
in this population-based study. All women aged 50-69 years diagnosed with breast
cancer from 1999-2008 and with follow-up data until the end of 2009 were
included. The primary endpoint was all-cause mortality. The results of a
mediation analysis indicated that the introduction of screening led to stage
distribution related reductions of -5.6 (95% confidence interval = -6.7 to -4.5),
-2.5 (-3.0 to -2.1), and -1.4 (-1.9 to -0.9) fewer deaths per 1000 women for with
a primary school education, secondary school education, and university education,
respectively. The study showed that stage distribution explained -5 (-5.9 to
4.1) fewer deaths among women with a university education and -2.4 (-2.9 to -2.0)
fewer deaths among women with a secondary school education before program
implementation when compared to the group with a primary school education. There
were significant reductions in mortality due to stage distribution after program
implementation with differences relative to women with primary school of -1.8 (
2.2 to -1.4) and -0.7 (-0.9 to -0.5) fewer deaths in favor of women with
university education and secondary school, respectively. The results indicate
reduced importance of cancer stage as a reason for differences in mortality by
socioeconomic status after the introduction of a public mammography program.
PMID- 29349167
TI - The weaker sex? Vulnerable men and women's resilience to socio-economic
disadvantage.
AB - Sex differences in mortality vary over time and place as a function of social,
health, and medical circumstances. The magnitude of these variations, and their
response to large socioeconomic changes, suggest that biological differences
cannot fully account for sex differences in survival. Drawing on a wide swath of
mortality data across countries and over time, we develop a set of empiric
observations with which any theory about excess male mortality and its correlates
will have to contend. We show that as societies develop, M/F survival first
declines and then increases, a "sex difference in mortality transition" embedded
within the demographic and epidemiologic transitions. After the onset of this
transition, cross-sectional variation in excess male mortality exhibits a
consistent pattern of greater female resilience to mortality under socio-economic
adversity. The causal mechanisms underlying these associations merit further
research.
PMID- 29349168
TI - Associations between physical health and depressive symptoms in Chinese older
adults: Do neighborhood resources matter?
AB - This is one of the first studies to examine the buffering effect of neighborhood
resources, specifically leisure amenities and voluntary associations, on the
relationship between poor physical health and depressive symptoms among older
persons in China. Using data from the 2011 baseline survey of the China Health
and Retirement Longitudinal Study, the analytical sample included 4715 older
adults aged 60 and over nested in 446 neighborhoods. Two-level linear regression
analyses were conducted in the urban (n=1225) and rural (n=3490) samples,
respectively. We found that leisure amenities significantly reduced the effect of
ADL limitations on depressive symptoms in urban older adults, and alleviated the
effect of chronic conditions on depressive symptoms in rural older Chinese.
PMID- 29349169
TI - Differences in neighborhood social cohesion and aerobic physical activity by
Latino subgroup.
AB - Previous research has examined the role of neighborhood social cohesion in
physical activity outcomes; however, less is known about this relationship across
Latino subgroups. The purpose of our study was to examine the association between
neighborhood social cohesion and aerobic leisure-time physical activity (LTPA)
among Latino adults and to determine whether these associations differ by Latino
subgroup. We used cross-sectional 2013-2014 National Health Interview Survey
(NHIS) data on Latinos originating from 5 countries/regions (i.e., Latinos of
Puerto Rican, Mexican/Mexican-American, Cuban/Cuban-American, Dominican and
Central or South American origin) aged >=18 years (n=11,126). Multivariable
logistic regression models were used to estimate associations between self
reported neighborhood social cohesion and meeting aerobic LTPA guidelines. Models
were adjusted for age, sex, education, and acculturation. We also investigated
whether associations varied by Latino subgroup. In adjusted models for all Latino
adults, compared with those reporting low social cohesion, individuals who
reported high social cohesion (Odds Ratio [OR]: 1.33; 95% Confidence Interval
[CI]: 1.17-1.52) were significantly more likely to meet the aerobic physical
activity guideline. When stratified by Latino subgroups, among Mexican/Mexicans
Americans (OR: 1.39; 95% CI: 1.16, 1.66) and Cuban/Cuban Americans (OR: 1.73; 95%
CI: 1.00, 2.97) high social cohesion was associated with meeting the aerobic
activity guideline. Among Dominicans, those who reported medium social cohesion
(OR: 0.52, 95% CI: 0.29, 0.93) were less likely to meet the aerobic activity
guideline. When examining aerobic physical activity outcomes in the Latino
population, the role of neighborhood social cohesion and the variability among
Latino subgroups should be considered.
PMID- 29349170
TI - The relationship between raising a child with a disability and the mental health
of mothers compared to raising a child without disability in japan.
AB - Objective: Previous studies conducted in Japan targeted only mothers who cared
for children with disabilities, and lacked reference subjects, such as mothers of
children without disabilities. The aim of this study was to examine the
association between raising one or two children with a disability and maternal
psychological distress compared to mothers of children without a disability, and
to assess differences among partnered mothers living with grandparent(s),
partnered mothers without grandparent(s), and single mothers. Methods: This study
utilized data from the Comprehensive Survey of Living Conditions (CSLC) in 2010.
We merged the data of the children (aged six and over), mothers, and fathers.
This study obtained 33,739 study subjects as a triad of a child (33,110 children
without disabilities and 629 children with disabilities), mother, and father. The
Japanese version of Kessler 6 (K6) was used to assess the psychological distress
of mothers. Multivariate logistic regression was performed to assess the
independent association of a child with a disability on maternal psychological
distress after controlling for the basic characteristics of the children,
mothers, and households. Results: This study reported that raising one or two
children with disabilities was significantly related to maternal psychological
distress (odds ratio: 1.72 for one child, 2.85 for two children) compared to
mothers of children without disability. After stratifying the analyses by family
structure, significant associations remained among mothers in two-parent families
but not for mothers in three-generation families and single mothers due to a
small number of children with disabilities in these families. Conclusions: This
study reported the significant association between raising a child with a
disability and maternal psychological distress in comparison to mothers of
children without disabilities. Attention should be paid to not only single
mothers, but also partnered mothers in two-parent families who have a child with
a disability. It is important for health professionals to focus on the mental
health of every mother of a child with a disability and to assess their needs for
psychological support.
PMID- 29349171
TI - Health returns to education by family socioeconomic origins, 1980-2008: Testing
the importance of gender, cohort, and age.
AB - Recent studies find that health returns to education are elevated among those who
come from disadvantaged families. These findings suggest that education may be a
health resource that compensates or "substitutes" for lower parental
socioeconomic status. Alternatively, some studies find support for a cumulative
(dis)advantage perspective, such that educational health returns are higher among
those who already were advantaged, widening initial health (dis)advantages across
the life course. However, it remains unclear whether these findings are dependent
on gender or cohort, and this is a fundamental oversight given marked differences
between men and women in educational and health inequalities across the twentieth
century. Drawing on national US data (1980-2002 General Social Survey with 2008
National Death Index Link), I indeed find that the presence or strength of
resource substitution or cumulative (dis)advantage depends upon health measure as
well as gender and cohort. For self-rated health, cumulative (dis)advantage
explains educational health disparities, but among men only. Cumulative
(dis)advantage in avoiding fair or poor health is partly explained by cohort and
age variation in health returns to education, and cumulative (dis)advantage in
excellent health is more robust in earlier cohorts and at older ages. For
mortality, resource substitution is instead supported, but for women only. Among
those from disadvantaged families, educational mortality buffering increases with
cohort but diminishes with age. Taken together, these findings confirm prior
research showing that adult health inequalities linked to education depend on
family background, and extend this work by demonstrating that the nature and
extent of these dynamics differ considerably depending on the health outcome
being assessed and on an individual's historical context, life course stage, and
gender.
PMID- 29349172
TI - The impact of work-related physical assaults on mental health among Japanese
employees with different socioeconomic status: The Japan Work Stress and Health
Cohort Study (JSTRESS).
AB - Background: Work-related physical assaults or violence has severely impacted on
the safety of the work environment and employees' mental health. The aim of the
present study was to investigate the prevalence of physical assaults, the effect
of socioeconomic status (SES) on it and depression associated with it in
employees working at large companies. Methods: A total of 22,770 Japanese
employees responded to a self-administered questionnaire including SES
(educational status and occupational status), violence victimization, worksite
social support and depression (response rate, 85%). The 12-month prevalence of
physical assaults and depression was examined using a single question and the
Center for Epidemiologic Studies Depression scale, respectively. Results: The
prevalence of physical assaults was 1.8% both in males and females. Although the
risk of exposure to physical assaults was 2-3 times higher in the blue-collar
group than in the manager group, the association of exposure to physical assaults
with depression was stronger in the manager and white-collar worker group
(Prevalence ratio [PR]=2.1 in males; 1.8 in females) than in the blue-collar
worker group (PR=1.7 in males; 1.5 in females) after adjusting demographic and
occupational covariates. A similar pattern was observed for education in males;
the association was stronger than in the lower education group (PR=2.1 and 1.8).
Conclusions: Low SES is a risk factor of exposure to physical assaults, however,
the association of physical assaults with depression was significantly greater
among company employees of higher SES than those of lower SES.
PMID- 29349173
TI - The impact of self-reported health and register-based prescription medicine
purchases on re-employment chances: A prospective study.
AB - In this paper, we investigate the influence of self-reported health and register
based prescription medicine purchases on re-employment chances, and whether these
health indicators measure similar aspects of health in this analysis. Data came
from a 2006 Danish unemployment survey among a random sample of unemployed
individuals enriched with register data (2006-2008, N=1806). The survey
participants all received unemployment benefits from the welfare system and had
been unemployed for more than 20 weeks at the time of the interview in 2006. We
combined these data with longitudinal register data on individual prescription
medicine purchases for somatic illnesses and prescription medicine purchases for
mental illnesses, information on re-employment and various socio-demographic
variables. We conducted binary logistic regression analyses to investigate the
impact of self-reported health and prescription medicine purchases measured in
2006 on re-employment chances in 2007 and 2008. Our analyses show that unemployed
workers with poor self-reported health and workers who had prescription medicine
purchases for mental illnesses were less likely to be re-employed in 2007 and
2008. Furthermore, the impact of both prescription medicine purchases for somatic
illnesses and for mental illnesses increased when adding self-reported health to
the model although prescription purchases for somatic illnesses became
statistically insignificant. The impact of prescription medicine purchases for
somatic illnesses was mediated by self-reported health, whilst prescription
medicine purchases for mental illnesses was only partly mediated. Finally, SRH
seemed a much stronger prediction than prescription medicines. From these
results, we propose, when possible, the inclusion of both an indicator of self
reported health and an indicator of mental health in studies on re-employment.
PMID- 29349174
TI - Self-identified race, socially assigned skin tone, and adult physiological
dysregulation: Assessing multiple dimensions of "race" in health disparities
research.
AB - Despite a general acceptance of "race" as a social, rather than biological
construct in the social sciences, racial health disparities research has given
less consideration to the dimensions of race that may be most important for
shaping persistent disparities in adult physical health status. In this study, we
incorporate the social constructionist view that race is multidimensional to
evaluate the health significance of two measures of race, racial self
identification and the socially perceived skin tone of black Americans, in a
sample of black and white adults in the Nashville Stress and Health Study
(N=1186). First, we use the approach most common in disparities research
comparing group differences in an outcome-to consider self-identified racial
differences in allostatic load (AL), a cumulative biological indicator of
physical dysregulation. Second, we examine intragroup variations in AL among
blacks by skin tone (i.e. light, brown, or dark skin). Third, we assess whether
the magnitude of black-white disparities are equal across black skin tone
subgroups. Consistent with prior research, we find significantly higher rates of
dysregulation among blacks. However, our results also show that racial
differences in AL vary by blacks' skin tone; AL disparities are largest between
whites and dark-skinned blacks and smallest between whites and light-skinned
blacks. This study highlights the importance of blacks' skin tone as a marker of
socially-assigned race for shaping intragroup and intergroup variations in adult
physiological dysregulation. These results demonstrate the importance of
assessing multiple dimensions of race in disparities research, as this approach
may better capture the various mechanisms by which "race" continues to shape
health.
PMID- 29349175
TI - The development of a bridging social capital questionnaire for use in population
health research.
AB - Bridging social capital is defined as the connections between individuals who are
dissimilar with respect to socioeconomic and other characteristics. There is an
important gap in the literature related to its measurement. We describe the
development and validation of a questionnaire to measure bridging social capital.
We focused the development of the questionnaire to be suitable for use in Latino
immigrant populations in the U.S. The structure of the questionnaire comprised
the following: Socialization in the job place (5 items); Membership in community
activities (16 items); Participation in community activities (5 items); Contact
with similar/different people (7 items); Assistance (17 items); Trust of
institutions, corporations and other people(14 items); and Trust of intimate
people (3 items). First, we used focus groups (N=17 participants) to establish
content validity with an inductive thematic analysis to identify themes and
subthemes. Changes were made to the questionnaire based on difficulty,
redundancy, length and semantic equivalence. Second, we analyzed the
questionnaire's psychometric properties (N=138). We tested internal consistency
with Cronbach alpha and construct validity with a Confirmatory Factor Analysis
(CFA) for each sub-scale to test theoretical unity; discriminant validity to
observe differences between participants from high and low SES backgrounds and
different language; and content validity with an independent expert panel.
Cronbach alphas ranged from 0.80 (Assistance) to 0.92 (Trust). CFA results
indicated that CFI and TLI were higher than 0.90 in almost all the scales, with
high factor loadings. The Wilcoxon tests indicated that there were statistically
significant mean differences between SES and language groups (p<0.00). The
independent expert panel determined that the questionnaire had good content
validity. This is the first demonstration of a psychometrically validated
questionnaire to measure bridging social capital in an immigrant population in
the United States. Our questionnaire may be suitable for further refinement and
adaptation to other immigrant groups in different countries.
PMID- 29349176
TI - Do age, psychosocial, and health characteristics alter the weak and strong tie
composition of network diversity and core network size in urban adults?
AB - Social capital and social support are two key constructs in the study of social
networks and health. Despite their importance, little research has sought to
examine the characteristics of those social ties by which individuals access
social capital and support resources. Network diversity - a key structural
feature in accessing social capital - refers to a person's broad but generally
weak and heterogeneous social ties; core network size - a key structural feature
in accessing social support - refers to the close, strong ties in personal
networks. Our study examines whether the tie strength composing network diversity
and core network size varies according to age-, psychosocial-, or health-related
characteristics. Data came from the Montreal Neighbourhood Networks and Healthy
Aging (MoNNET-HA) study, a representative sample of 2707 Montreal, Canada adults.
Position and name generators were used to collect data on network diversity and
core networks, and whether access to social resources was through kin, friends,
or acquaintances. Multilevel negative binomial regression was used to account for
the counts of different tie strengths nested within individuals and tracts.
Network diversity and core network size both declined with older age groups, with
those declines being more noticeable in not having ties at all or fewer ties with
friends. Psychosocial and health factors altered the relative contribution of
kin, friends and acquaintances to network diversity and core network size in
similar patterns. Understanding the tie composition of network diversity and core
network size can contribute to our knowledge of the social mechanisms linking
social capital and support to health outcomes.
PMID- 29349177
TI - Contextual generalized trust and immunization against the 2009 A(H1N1) pandemic
in the American states: A multilevel approach.
AB - The aim of the study was to investigate the association between contextual
generalized trust and individual-level 2009 A(H1N1) pandemic immunization
acceptance. A second aim was to investigate whether knowledge about the A(H1N1)
pandemic mediated the association between contextual generalized trust and
A(H1N1) immunization acceptance. Data from the National 2009 H1N1 Flu Survey was
used. To capture contextual generalized trust, data comes from an aggregation of
surveys measuring generalized trust in the American states. To investigate the
association between contextual generalized trust and immunization acceptance,
while taking potential individual-level confounders into account, multilevel
logistic regression was used. The investigation showed contextual generalized
trust to be significantly associated with immunization acceptance. However,
controlling for knowledge about the A(H1N1) pandemic did not substantially affect
the association between contextual generalized trust and immunization acceptance.
In conclusion, contextual state-level generalized trust was associated with
A(H1N1) immunization, but knowledge about A(H1N1) was not mediating this
association.
PMID- 29349178
TI - Trends in socioeconomic inequalities in self-rated health, smoking, and physical
activity of Japanese adults from 2000 to 2010.
AB - Health disparities in Japan are attracting increasing attention. Temporal trends
in health disparities should be continuously monitored using multiple indices of
socioeconomic status (SES) and health-related outcomes. We explored changes in
socioeconomic differences in the health of Japanese adults during 2000-2010. The
data was taken from the Japanese General Social Surveys, the cross-sectional
surveys for nationally representative samples of Japanese adults. We used 14,193
samples (individuals of 20-64 years of age) in our analysis. We estimated age
adjusted prevalence ratios of the lowest SES group in comparison with the highest
SES group using Poisson regression models with robust error variance. Relative
index of inequality (RII) and slope index of inequality (SII) were also
calculated. We examined the changes in the association between health-related
outcomes (self-rated health (SRH), smoking, and physical activity) and SES
indices (income, education, occupation, and subjective social class
identification). The results showed temporally expanding trends for the
associations of current smoking with SES, especially among women, in both
relative and absolute measures. In contrast, no expanding trends were seen for
SRH and physical activity. Although the smoking rates declined through the first
decade of the 21st century, the socioeconomic disparities in smoking prevalence
among Japanese adults expanded, especially among women. Researchers and
policymakers should continuously monitor the trends that may cause future
disparities in smoking-related morbidity and mortality.
PMID- 29349179
TI - Do flexicurity policies protect workers from the adverse health consequences of
temporary employment? A cross-national comparative analysis.
AB - Flexicurity policies comprise a relatively novel approach to the regulation of
work and welfare that aims to combine labour market flexibility with social
security. Advocates of this approach argue that, by striking the right balance
between flexibility and security, flexicurity policies allow firms to take
advantage of loose contractual arrangements in an increasingly competitive
economic environment while simultaneously protecting workers from the adverse
health and social consequences of flexible forms of employment. In this study, we
use multilevel Poisson regression models to test the theoretical claim of the
flexicurity approach using data for 23 countries across three waves of the
European Social Survey. We construct an institutional typology of labour market
regulation and social security to evaluate whether inequalities in self-reported
health and limiting longstanding illness between temporary workers and their
permanent counterparts are smaller in countries that most closely approximate the
ideal type described by advocates of the flexicurity approach. Our results
indicate that, while the association between temporary employment and health
varies across countries, institutional configurations of labour market regulation
and social security do not provide a meaningful explanation for this cross
national variation. Contrary to the expectations of the flexicurity hypothesis,
our data do not indicate that employment-related inequalities are smaller in
countries that approximate the flexicurity approach. We discuss potential
explanations for these findings and conclude that there remains a relative lack
of evidence in support of the theoretical claims of the flexicurity approach.
PMID- 29349180
TI - Neighborhood racial composition and poverty in association with pre-pregnancy
weight and gestational weight gain.
AB - Background: Studies of neighborhood racial composition or neighborhood poverty in
association with pregnancy-related weight are limited. Prior studies of
neighborhood racial density and poverty has been in association with adverse
birth outcomes and suggest that neighborhoods with high rates of poverty and
racial composition of black residents are typically segregated and systematically
isolated from opportunities and resources. These neighborhood factors may help
explain the racial disparities in pre-pregnancy weight and inadequate weight
gain. This study examined whether neighborhood racial composition and
neighborhood poverty was associated with weight before pregnancy and weight gain
during pregnancy and if this association differed by race. Methods: We used vital
birth records of singleton births of 73,061 non-Hispanic black and white women in
Allegheny County, PA (2003-2010). Maternal race and ethnicity, pre-pregnancy body
mass-index (BMI), gestational weight gain and other individual-level
characteristics were derived from vital birth record data, and measures of
neighborhood racial composition (percentage of black residents in the
neighborhood) and poverty (percentage of households in the neighborhood below the
federal poverty) were derived using US Census data. Multilevel log binomial
regression models were performed to estimate neighborhood racial composition and
poverty in association with pre-pregnancy weight (i.e., overweight/obese) and
gestational weight gain (i.e., inadequate and excessive). Results: Black women as
compared to white women were more likely to be overweight/obese before pregnancy
and to have inadequate gestational weight gain (53.6% vs. 38.8%; 22.5% vs. 14.75
respectively). Black women living in predominately black neighborhoods were
slightly more likely to be obese prior to pregnancy compared to black women
living in predominately white neighborhoods (PR 1.10; 95% CI: 1.03, 1.16). Black
and white women living in high poverty areas compared with women living in lower
poverty areas were more likely to be obese prior to pregnancy; while only white
women living in high poverty areas compared to low poverty areas were more likely
gain an inadequate amount of weight during pregnancy. Conclusions: Neighborhood
racial composition and poverty may be important in understanding racial
differences in weight among childbearing women.
PMID- 29349181
TI - Indicators of subjective social status: Differential associations across race and
sex.
AB - Background: Subjective social status (SSS), or perception of rank on the social
hierarchy, is an important indicator of various health outcomes. However, the
psychosocial influences on this construct are unclear, and how these influences
vary across different sociodemographic groups is poorly understood. Methods:
Participants were 2077 African-American and Whites (M age=47.85; 57% female; 58%
African American, and 58% above poverty) from the Healthy Aging in Neighborhoods
of Diversity across the Life Span (HANDLS) study. Multiple regression analyses
examined (1) hypothesized psychosocial indicators of SSS and (2) the moderating
effect of race and sex on the variables associated with SSS. Results: In addition
to the traditional measures of SES (i.e. income, employment, and education),
psychosocial variables (i.e. depressive symptomatology, neighborhood
satisfaction, and self-rated health) were significantly associated with SSS.
However, some of these indicators varied with respect to race and sex. Three
significant interactions were found: sex by employment, race by employment, and
race by education, wherein objective measures of SES were more associated with
SSS for Whites and men compared to African Americans and women. Conclusion:
Psychosocial measures may influence individuals' perceptions of themselves on the
social hierarchy. Additionally, SSS may vary by demographic group. When
considering the impact of SSS on health, it is important to consider the unique
interpretations that various demographic groups have when perceiving themselves
on the social hierarchy.
PMID- 29349182
TI - Life-course social and economic circumstances, gender, and resilience in older
adults: The longitudinal International Mobility in Aging Study (IMIAS).
AB - Although early socioeconomic adversity is associated with poorer function and
health in adulthood, those who are able to adapt positively to such risks and
threats develop a resilience that may ameliorate harm. Predictors of resilience
have been examined in children, however exploring the relationship between life
course events, lived environments and current resilience among older adults
across countries is novel. We specifically studied how childhood social and/or
economic adversity and current socioeconomic resources were associated with
resilience in 2000 community dwelling older men and women in Canada, Colombia,
Brazil and Albania. The longitudinal International Mobility in Aging Study
(IMIAS) collected information in 2012 and 2014 on childhood adversity, current
income sufficiency social support and social engagement, and resilience (Wagnild
Resilience Scale RS-14). Resilience levels were moderately high, and similar
among women and men. Early social adversity predicted later resilience for some,
with women but not men adapting positively. In contrast there was no bouncing
back from early economic adversity. Current social engagement aligned with
resilience (women only) as did social support from children (for women) and
friends (for men). Partner support was of no advantage to either. Among men
economic circumstances were stronger correlates of resilience while for women
social circumstances were primary. The impact of site on resilience suggested
that cultural norms and values have an independent effect on resilience of their
populations, with strong and positive social ties more typical of Latin America
than Canada appearing to offset lower absolute incomes. These findings are of
importance because resilience is dynamic, can be fostered across the lifespan and
is generally associated with greater health. Understanding which social assets
and resources can be reinforced to build individual resilience offers a means for
decreasing the harms of social and economic adversity.
PMID- 29349183
TI - The association between social cohesion and physical activity in canada: A
multilevel analysis.
AB - Although previous research has shown that social cohesion may promote physical
activity, social cohesion at the individual level was not always differentiated
from social cohesion at the community level, and studies were often limited to
specific population subgroups or geographical areas. We addressed the above
limitations through the use of a multilevel modelling approach and nationally
representative data from the 2009-2014 Canadian Community Health Survey. Physical
activity level was operationalized as average daily energy expenditure; social
cohesion was assessed by self-rated sense of belonging to the local community;
and communities were represented by Canada's Forward Sortation Areas. The sample
included 245,150 respondents from 1570 communities. Geographical location was
found to explain a significant proportion (4.1%) of the overall variance in
physical activity level. After adjusting for age, sex, household income,
education and urban-rural status, both individual- and community-level social
cohesion were found to be positively associated with physical activity (p<0.001
for both). Thus, efforts to promote social cohesion and integration within
communities may also promote physical activity and overall health.
PMID- 29349184
TI - Using photovoice methods to explore older people's perceptions of respect and
social inclusion in cities: Opportunities, challenges and solutions.
AB - Urbanisation and population ageing have contributed to recognise cities as
important settings for healthy ageing. This paper considers opportunities,
challenges and solutions of using photovoice methods for exploring how
individuals perceive their cities and the contribution this makes to their
health. It focuses on one aspect of older people's experiences - respect and
social inclusion, in the context of a community-based participatory research.
Drawing on selected findings (participants' photographs, associated quotes and
researchers' field notes), we provide an assessment of the suitability of
photovoice methodology for the intended purpose. Four groups of older people
(n=26; aged 60 years or more) from four contrasting geographical areas in
Liverpool, UK, were recruited purposively. Participants photographed perceived
positive and negative aspects of respect and social inclusion in the city,
reflecting on the meanings of the photographs in individual (n=23) and group
interviews (n=9). Thematic and content analysis was conducted using NVivo 10
software. The work reported here provides insights into how participants engage
with the photovoice process; factors preventing taking photos of interest; and
how photographs complement interviews and focus groups. The findings demonstrate
that photovoice both facilitated the dissemination of personalised relevant
knowledge, and encouraged critical dialogue between participants, and city
stakeholders. Reported difficulties included photography of negative and social
concepts, and anxiety when taking photographs due to (i) expectations of what is
a 'proper' photograph, and (ii) the need to obtain consent from subjects. With
preparation, training, and discussion of participants' ideas not expressed
through photographs, photovoice was well-suited to this topic, providing insights
complementing other research methods. Through analysing the application of
photovoice for exploring perceptions of respect and social inclusion in cities,
our paper has identified potential issues and provides important recommendations
for researchers on how photovoice methodology can be strengthened in exploring
conditions for better health in the urban environment.
PMID- 29349185
TI - Differences in stroke and ischemic heart disease mortality by occupation and
industry among Japanese working-aged men.
AB - Occupation- and industry-based risks for stroke and ischemic heart disease may
vary among Japanese working-aged men. We examined the differences in mortality
rates between stroke and ischemic heart disease by occupation and industry among
employed Japanese men aged 25-59 years. In 2010, we obtained occupation- and
industry-specific vital statistics data from the Japanese Ministry of Health,
Labour, and Welfare dataset. We analyzed data for Japanese men who were aged 25
59 years in 2010, grouped in 5-year age intervals. We estimated the mortality
rates of stroke and ischemic heart disease in each age group for occupation and
industry categories as defined in the national census. We did not have detailed
individual-level variables. We used the number of employees in 2010 as the
denominator and the number of events as the numerator, assuming a Poisson
distribution. We conducted separate regression models to estimate the incident
relative risk for stroke and ischemic heart disease for each category compared
with the reference categories "sales" (occupation) and "wholesale and retail"
(industry). When compared with the reference groups, we found that occupations
and industries with a relatively higher risk of stroke and ischemic heart disease
were: service, administrative and managerial, agriculture and fisheries,
construction and mining, electricity and gas, transport, and professional and
engineering. This suggests there are occupation- and industry-based mortality
risk differences of stroke and ischemic heart disease for Japanese working-aged
men. These differences in risk might be explained to factors associated with
specific occupations or industries, such as lifestyles or work styles, which
should be explored in further research. The mortality risk differences of stroke
and ischemic heart disease shown in the present study may reflect an excessive
risk of Karoshi (death from overwork).
PMID- 29349186
TI - The shape of the association between income and mortality in old age: A
longitudinal Swedish national register study.
AB - This study used data on the total population to examine the longitudinal
association between midlife income and mortality and late-life income and
mortality in an aging Swedish cohort. We specifically examined the shape of the
associations between income and mortality with focus on where in the income
distribution that higher incomes began to provide diminishing returns. The study
is based on a total Swedish population cohort between the ages of 50 and 60 years
in 1990 (n=801,017) followed in registers for up to 19 years. We measured
equivalent disposable household income in 1990 and 2005 and mortality between
2006 and 2009. Cox proportional hazard models with penalized splines (P-spline)
enabled us to examine for non-linearity in the relationship between income and
mortality. The results showed a clear non-linear association. The shape of the
association between midlife (ages 50-60) income and mortality was curvilinear;
returns diminished as income increased. The shape of the association between late
life (ages 65-75) income and mortality was also curvilinear; returns diminished
as income increased. The association between late-life income and mortality
remained after controlling for midlife income. In summary, the results indicated
that a non-linear association between income and mortality is maintained into old
age, in which higher incomes give diminishing returns.
PMID- 29349187
TI - An agent-based simulation of persistent inequalities in health behavior:
Understanding the interdependent roles of segregation, clustering, and social
influence.
AB - Health inequalities are conspicuously persistent through time and often durable
even in spite of interventions. In this study, I use agent-based simulation
models (ABMs) to understand how the complex interrelationships between
residential segregation, social network formation, group-level preferences, and
social influence may contribute to this persistence. I use a more-stylized ABM,
Bubblegum Village (BV), to understand how initial inequalities in bubblegum
chewing behaviors either endure, increase, or decrease over time given group
level differences in preferences, neighborhood-level barriers or facilitators of
bubblegum chewing (e.g., access to bubblegum shops), and agents' preferences for
segregation, homophily, and clustering (i.e., the 'tightness' of social
networks). I further use BV to understand whether segregation and social network
characteristics impact whether the effects of a bubblegum-reduction intervention
that is very effective in the short term are durable over time, as well as to
identify intervention strategies to reduce attenuation of the intervention
effects. In addition to BV, I also present results from an ABM based on the
distribution and social characteristics of the population in Philadelphia, PA.
This model explores similar questions to BV, but examines racial/ethnic
inequalities in soda consumption based on agents' social characteristics and
baseline soda consumption probabilities informed by the 2007-2010 National Health
and Nutrition Examination Survey. Collectively, the models suggest that
residential segregation is a fundamental process for the production and
persistence of health inequalities. The other major conclusion of the study is
that, for behaviors that are subject to social influence and that cluster within
social groups, interventions that are randomly-targeted to individuals with 'bad'
behaviors will likely experience a large degree of recidivism to pre-intervention
behaviors. In contrast, interventions that target multiple members of the same
network, as well as multilevel interventions that include a neighborhood-level
component, can reduce recidivism.
PMID- 29349188
TI - Dietary quality in children and the role of the local food environment.
AB - Diet is a modifiable contributor to many chronic diseases including childhood
obesity. The local food environment may influence children's diet but this area
of research is understudied. This study explores if distance to and the number of
supermarkets and convenience stores in the local area around households are
associated with dietary quality in nine year olds whilst controlling for
household level socio-economic factors. This is a secondary analysis of Wave 1
(2007/2008) of the Growing Up in Ireland (GUI) Child Cohort Study, a sample of
8568 nine year olds from the Republic of Ireland. Dietary intake was assessed
using a short, 20-item parent reported food frequency questionnaire and was used
to create a dietary quality score (DQS) whereby a higher score indicated a higher
diet quality. Socio-economic status was measured using household class, household
income, and maternal education. Food availability was measured as road network
distance to and the number of supermarkets and convenience stores around
households. Separate fixed effects regression models assessed the association
between local area food availability and dietary quality, stratified by sex. The
DQS ranged from -5 to 25 (mean 9.4, SD 4.2). Mean DQS was higher in those who
lived furthest (distance in quintiles) from their nearest supermarket (p<0.001),
and in those who lived furthest from their nearest convenience store (p<0.001).
After controlling for socio-economic characteristics of the household, there was
insufficient evidence to suggest that distance to the nearest supermarket or
convenience store was associated with dietary quality in girls or boys. The
number of supermarkets or convenience stores within 1000 m of the household was
not associated with dietary quality. Food availability had a limited effect on
dietary quality in this study. Issues associated with conceptualising and
measuring the food environment may explain the findings of the current study.
PMID- 29349189
TI - Does employment security modify the effect of housing affordability on mental
health?
AB - This paper uses longitudinal data to examine the interrelationship between two
central social determinants of mental health - employment security and housing
affordability. Data from ten annual waves of the longitudinal Household, Income
and Labour Dynamics in Australia (HILDA) survey (which commenced in 2000/1 and is
ongoing) were analysed using fixed-effects longitudinal linear regression. Change
in the SF-36 Mental Component Summary (MCS) score of working age individuals (25
64 years) (51,885 observations of 10,776 people), associated with changes in
housing affordability was examined. Models were adjusted for income, age, survey
year, experience of serious injury/illness and separation/divorce. We tested for
an additive interaction between the security of a household's employment
arrangements and housing affordability. People in insecurely employed households
appear more vulnerable than people in securely employed households to negative
mental health effects of housing becoming unaffordable. In adjusted models,
people in insecurely employed households whose housing became unaffordable
experienced a decline in mental health (B=-1.06, 95% CI -1.75 to -0.38) while
people in securely employed households experienced no difference on average. To
progress our understanding of the Social Determinants of Health this analysis
provides evidence of the need to bridge the (largely artificial) separation of
social determinants, and understand how they are related.
PMID- 29349190
TI - Barriers to uptake of antenatal maternal screening tests in Senegal.
AB - Background: Evidence exists that selective antenatal maternal screening tests
contribute to the reduction of maternal morbidity and mortality. However, data
are lacking on coverage with the complete set of recommended tests. The study
aimed to identify barriers to uptake of the complete set of tests recommended by
the Ministry of Health in Senegal. Methods: Data were collected in communities,
antenatal care (ANC) clinics and the laboratories of 11 public health care
facilities across Senegal. Mixed-methods included ethnography (observations and
informal conversations), in-depth interviews and workshops at the health
facilities; structured interviews with 283 women receiving antenatal tests
("women in the lab"); in-depth interviews with 81 women in communities who were
pregnant or had recently delivered ("community women"). Results: Only 13% of
community women and 22% of women in the lab had received the complete set of
tests. For various social, financial and antenatal care-related reasons 38% of
community women who visited antenatal care facilities did not access a
laboratory. The lowest test uptake was in women receiving antenatal care at
health posts. Barriers at the laboratory level were the cost of the test, stock
outs of reagents, and broken equipment. Midwives were the main gatekeepers of the
laboratory, not requesting (all) tests because of assumptions about women's
financial problems and reliance on clinical symptoms. Conclusion: In Senegal,
recommended antenatal maternal screening tests are substantially underutilized.
Efforts to increase test uptake should include accessible testing guidelines,
reducing the cost of tests, raising awareness about the reasons for tests, and
making the complete test set in point-of-care format accessible in peripheral
health posts. National and international antenatal care policies and programs
should facilitate access to maternal screening tests as a contribution to
reducing maternal and infant morbidity and mortality.
PMID- 29349191
TI - Trends in psychological distress and alcoholism after The Great East Japan
Earthquake of 2011.
AB - Aims: Many studies have shown that natural disasters affect mental health;
however, longitudinal data on post-disaster mental health problems are scarce.
The aims of our study were to investigate the trend in psychological distress and
alcoholism after The Great East Japan Earthquake and tsunami in north eastern
Japan, in March 2011. Methods: A longitudinal study was conducted using annual
health check data for the general population, in the city of Higashi-Matsushima,
which was affected by the high impact of tsunami. In 2012 and 2013, the Kessler
Psychological Distress Scale and the CAGE questionnaire (for screening for
alcoholism) were used to assess psychological distress and prevalence of
alcoholism. Results: Of 11,855 total eligible residents, 2192 received the annual
check in 2012 and 2013. The prevalence of mental illness and the mean score of
alcoholism tendency increased during the follow-up period. The majority of
respondents (43.8%) with baseline serious mental illness (SMI) continued to have
SMI at follow-up; only 16.7% reported recovering. Older age, female sex, and
severity of home damage predicted higher psychological distress, while male sex
was a risk factor for alcoholism at follow-up. Conclusions: Psychological
distress deteriorated 2 years after the huge natural disaster, compared with 1
year after the disaster. Long-term mental health care is needed for those
affected by natural disasters, particularly those who have suffered loss.
PMID- 29349192
TI - Changing medical relationships after the ACA: Transforming perspectives for
population health.
AB - American health care has undergone significant organizational change in recent
decades. But what is the state of core medical relationships in the wake of these
changes? Throughout ACA-era health care reform, the doctor-patient relationship
was targeted as a particularly important focus for improving communication and
health outcomes. Recent developments however have shifted the focus from
individual-level outcomes to the wellbeing of populations. This, we argue,
requires a fundamental rethinking of health care reform as an opportunity to
renegotiate relationships. For example, the move to population medicine requires
that the very concept of a patient be resituated and the scope of relevant
relationships expanded. Medical relationships in this era of health care are
likely to include partnerships between various types of clinicians and the
communities in which patients reside, as well as a host of new actors, from
social workers and navigators to scribes and community health workers. To address
the upstream determinants of population health, providers must be increasingly
willing and trained to collaborate with community stakeholders to address both
medical and non-medical issues. These community-based partnerships are critical
to providing health care that is both relevant and appropriate for addressing
problems, and sustainable. Approaching health care reform, and the focus on
population health, as a fundamental reworking of relationships provides scholars
with a sharper theoretical lens for understanding 21st century American health
care.
PMID- 29349193
TI - An analysis of weight perception and physical activity and dietary behaviours
among youth in the COMPASS study.
AB - Purpose: Weight misperceptions appear common among youth, potentially influencing
their motivation to engage in health-related behaviours; however, the direction
of impact remains unclear. The current study examined how weight perception
influences physical activity (PA) and diet among youth. Methods: This study used
2-year linked data of 19,322 grade 9-12 students from Year 2 (Y2:2013-2014) and 3
(Y3:2014-2015) of the COMPASS study. Generalized Estimating Equation models
tested the effect of Y3 weight perception on the various Y3 PA and dietary
behaviour measures, adjusting for Y3 covariates (grade, race/ethnicity, weekly
spending money), school cluster, school area median household income, and the Y2
outcome. Models were stratified by gender and body mass index (BMI)
classification. Results: Regardless of BMI status, overweight perceptions among
boys and girls were associated with lower likelihoods of playing school sports,
physical education class enrollment, meeting resistance exercise recommendations,
eating breakfast regularly, and less vigorous-intensity PA, and among boys only,
lower odds of meeting PA guidelines, compared to their peers who perceived their
weight as "about right". In boys with normal-weight BMIs, underweight perceptions
predicted less vigorous-intensity PA, and lower odds of physical education class
enrollment, and of meeting PA and resistance exercise recommendations, than
"about right" perceptions. Among girls, underweight perceptions predicted lower
likelihoods of engaging in adequate resistance exercise and playing intramurals,
and greater odds of eating fast food on weekends, purchasing snacks, and drinking
energy drinks and sugar-sweetened beverages. Girls with overweight/obese BMIs who
perceived their weight as such were less likely to consume adequate fruits and
vegetables relative to their counterparts with "about right" weight perceptions.
Conclusions: Overall, weight perceptions of "about right" appear more favourable
for health behaviours among youth across the weight range. Results suggest
obesity prevention strategies aiming to increase awareness of weight status may
have unintended effects.
PMID- 29349194
TI - The interplay of race, socioeconomic status and neighborhood residence upon birth
outcomes in a high black infant mortality community.
AB - This study examined the interrelationship of race and socioeconomic status (SES)
upon infant birthweight at the individual and neighborhood levels within a
Midwestern US county marked by high Black infant mortality. The study conducted a
multi-level analysis utilizing individual birth records and census tract datasets
from 2010, linked through a spatial join with ArcGIS 10.0. The maternal
population of 2861 Black and White women delivering infants in 2010, residing in
57 census tracts within the county, constituted the study samples. The main
outcome was infant birthweight. The predictors, race and SES were dichotomized
into Black and White, low-SES and higher-SES, at both the individual and census
tract levels. A two-part Bayesian model demonstrated that individual-level race
and SES were more influential birthweight predictors than community-level
factors. Specifically, Black women had 1.6 higher odds of delivering a low
birthweight (LBW) infant than White women, and low-SES women had 1.7 higher odds
of delivering a LBW infant than higher-SES women. Moderate support was found for
a three-way interaction between individual-level race, SES and community-level
race, such that Black women achieved equity with White women (4.0% Black LBW and
4.1% White LBW) when they each had higher-SES and lived in a racially congruous
neighborhood (e.g., Black women lived in disproportionately Black neighborhood
and White women lived in disproportionately White neighborhood). In sharp
contrast, Black women with higher-SES who lived in a racially incongruous
neighborhood (e.g., disproportionately White) had the worst outcomes (14.5% LBW).
Demonstrating the layered influence of personal and community circumstances upon
health, in a community with substantial racial disparities, personal race and SES
independently contribute to birth outcomes, while environmental context,
specifically neighborhood racial congruity, is associated with mitigated health
risk.
PMID- 29349195
TI - Inter-individual inequality in BMI: An analysis of Indonesian Family Life Surveys
(1993-2007).
AB - Widening inequalities in mean Body Mass Index (BMI) between social and economic
groups are well documented. However, whether changes in mean BMI are followed by
changes in dispersion (or variance) and whether these inequalities are also
occurring within social groups or across individuals remain understudied. In
addition, a substantial body of literature exists on the global increase in mean
BMI and prevalence of overweight and obesity. However, whether this weight gain
is shared proportionately across the whole spectrum of BMI distribution, also
remains understudied. We examined changes in the distribution of BMI at the
population level over time to understand how changes in the dispersion reflect
between-group compared to within-group inequalities in weight gain. Moreover, we
investigated the entire distribution of BMI to determine in which percentiles the
most weight gain is occurring over time. Utilizing four waves (from 1993 to 2007)
of Indonesian Family Life Surveys (IFLS), we estimated changes in the mean and
the variance of BMI over time and across various socioeconomic groups based on
education and households' expenditure per capita in 53,648 men and women aged 20
50 years. An increase in mean and standard deviation was observed among men (by
4.3% and 25%, respectively) and women (by 7.3% and 20%, respectively) over time.
Quantile-Quantile plots showed that higher percentiles had greater increases in
BMI compared to the segment of the population at lower percentiles. While between
socioeconomic group differences decreased over time, within-group differences
increased and were more prominent among individuals with poor education and lower
per capita expenditures. Population changes in BMI cannot be fully described by
average trends or single parameters such as the mean BMI. Moreover, greater
increases in within-group dispersion compared with between-group differences
imply that growing inequalities are not merely driven by these socioeconomic
factors at the population level.
PMID- 29349196
TI - The association between anti-immigrant policies and perceived discrimination
among Latinos in the US: A multilevel analysis.
AB - Research has found a strong inverse association between discrimination and health
and well-being. Most of these studies have been conducted among African
Americans, and have examined the relationship at the individual-level. To fill
these gaps in knowledge we estimated the prevalence of perceived discrimination
among a nationally representative sample of Latino adults in the US, and
investigated the association between state-level anti-immigrant policies and
perceived discrimination. We merged survey data with a state-level anti-immigrant
policy index. First, we fit hierarchical logistic regression models to test the
crude and adjusted association between anti-immigrant policies and perceived
discrimination. Second, we specified cross-level interaction terms to test
whether this association differed by relevant individual characteristics. Almost
70% of respondents reported discrimination (68.4%). More anti-immigrant policies
were associated with higher levels of discrimination (OR=1.62, 95% CI 1.16, 2.24,
p=0.01). The association between anti-immigrant policies and discrimination
differed by place of origin (p=0.001) and was marginally moderated by generation
status (p=0.124). Anti-immigrant policies stigmatize both foreign and US-born
Latinos by creating a hostile social environment which affects their experiences
of discrimination. These non-health policies can adversely affect Latino health,
in part through exposure to discrimination, and may help explain health patterns
among Latinos in the US.
PMID- 29349197
TI - Income disparities in cardiovascular health across the lifespan.
AB - Using data from the 1999-2014 National Health and Nutrition Examination Survey (n
~ 46,000), this study documents income disparities in the age patterning of
cardiovascular conditions across the lifespan in the U.S. The conditions were
assessed from laboratory test results, self-reports of medications used to treat
specific conditions, and anthropometric measurements, allowing us to capture
whether individuals at given ages had developed the various conditions,
regardless of previous diagnosis and treatment. We found evidence of large income
disparities in the presence of cardiovascular conditions and risk factors for
females, smaller disparities in the same conditions for males, and few
disparities that increased with age for either gender. Results were very similar
when considering disparities by education instead of income. The findings suggest
that the widening socioeconomic gradients in health over the lifespan found in
many previous studies-which have generally focused on self-rated health, activity
limitations, or diagnosed conditions-reflect, at least to some extent,
differences in diagnosis, treatment, and management of health conditions rather
than age-related differences in developing them. The findings also suggest that
preventive healthcare is not an important source of socioeconomic disparities in
cardiovascular health in the U.S., at least for men. The observed patterns of
income disparities in cardiovascular conditions over the lifespan are more
consistent with theories of early life conditions and the imprinting of health
endowments and susceptibilities early in life than with cumulative life exposure
or stress hypotheses.
PMID- 29349198
TI - Invited commentary: The long term impact of forced migration during childhood on
adult health.
AB - Saarela and Elo (SSM-Population Health; Volume 2, December 2016, Pages 813-823)
provide new evidence of early life forced displacement not being adversely
associated with adult health. Their study highlights some of the challenges to
identifying a causal effect of childhood exposure on adult health in the context
of complex emergencies. Importantly, it opens up for future research that can
address commonly recognized sources of bias and identify intervening pathways
linking forced migration with adult health outcomes.
PMID- 29349199
TI - Efficiency or equity? Simulating the impact of high-risk and population
intervention strategies for the prevention of disease.
AB - Maximizing both efficiency and equity are core considerations for population
health. These considerations can result in tension in population health science
as we seek to improve overall population health while achieving equitable health
distributions within populations. Limited work has explored empirically the
consequences of different population health intervention strategies on the burden
of disease and on within- and between-group differences in disease. To address
this gap, we compared the impact of four simulated interventions using data from
the National Health and Nutrition Examination Survey. In particular, we focus on
assessing how population and high-risk primary prevention and population and high
risk secondary interventions efforts to reduce smoking behavior influence
systolic blood pressure (SBP) and hypertension, and how such strategies influence
inequalities in SBP by income. The greatest reductions in SBP mean and standard
deviation resulted from the population secondary prevention. High-risk primary
and secondary prevention and population secondary prevention programs all yielded
substantial reductions in hypertension prevalence. The effect of population
primary prevention did little to decrease population SBP mean and standard
deviation, as well as hypertension prevalence. Both high-risk strategies had a
larger impact in the low-income population, leading to the greatest narrowing the
income-related gap in disease. The population prevention strategies had a larger
impact in the high-income population. Population health approaches must consider
the potential impact on both the whole population and also on those with
different levels of risk for disease within a population, including those in
under-represented or under-served groups.
PMID- 29349200
TI - Changes in living arrangements and mortality among older people in China.
AB - Living arrangements in later life are dynamic, with changes associated with life
events such as widowhood or moves into an institution. Previous research has
found particular changes in living arrangements to be associated with an elevated
risk of mortality. However, research in this area within the context of China is
limited, despite China being home to the world's largest population of older
people. This study investigates the impact of changes in living arrangements on
older persons' survival using the Chinese Longitudinal Healthy Longevity Survey
from 2002 to 2011. The original sample was 16,064 in 2002, and this study
includes 6191 individuals who survived in 2005 and had complete information of
track record in later waves. Changes in living arrangements are examined between
2002 and 2005. Cox-proportional hazards models are then used to investigate the
association between the dynamics of living arrangements and respondents' survival
status from 2005 to 2011 . Results show that men and women who lived in an
institution in both 2002 and 2005, or who moved into an institution from living
with family faced a greater risk of dying compared to those continuing to live
with family. By contrast, continuing to live with family or alone, or moving
between living with family and living alone, were not associated with an
increased mortality risk, although there were some differences by gender. The
institutional care sector in China is still in its infancy, with provision based
on ability to pay market fees rather than need associated with age-related
function impairment. The findings show that living in, or moving into, an
institution is associated with a high mortality risk therefore requires further
investigation in the context of a rapidly changing Chinese society.
PMID- 29349201
TI - Factors affecting the physical and mental health of older adults in China: The
importance of marital status, child proximity, and gender.
AB - Evidence is accumulating about the association between strong family ties and the
emotional and physical welfare of older adults, and researchers have identified
negative consequences of being unmarried, being childless, and/or living alone.
These associations have been recognized in multiple contexts, including in Asia
where living with a spouse and/or grown children has been shown in some studies
to improve elderly well-being. Social support, especially family support, is
expected to continue to be important where populations are aging and social
safety nets are weak. Using longitudinal data from the 2010 and 2012 waves of the
China Family Panel Studies, we focus on the effects of marital status at times 1
and 2, changes in marital status between the two surveys, and other family
related indicators of social connectedness on ratings of depression, levels of
life satisfaction, and self-reported physical health among those aged 50 and
over. Our sample includes 9831 respondents who have valid data on wellbeing
indicators for Wave 1 and Wave 2, as well as complete information on the other
covariates controlled in our analysis. In analyses of the full sample, those who
were married at both points in time reported lower depression scores than those
who were never-married, divorced, or widowed at both time points, and those whose
unions dissolved in the interval. Those who were married at both times also
generally reported greater levels of life satisfaction than those who were never
married at both time points and those who became divorced during the interval.
Important underlying gender differences are observed both for life satisfaction
and depression. In addition, those who were married at both time points reported
being in better physical health than those who became widowed during the interval
(significant primarily for women), and those who had never been married
(significant primarily for men). Our study contributes to the literature on
social ties and the wellbeing by highlighting the importance of marital status
and changing marital status, net of child co-residence and proximity, in China.
PMID- 29349202
TI - Healthcare access: A sequence-sensitive approach.
AB - It is widely accepted that healthcare-seeking behaviour is neither limited to nor
terminated by access to one single healthcare provider. Yet the sequential
conceptualisation of healthcare-seeking processes has not diffused into
quantitative research, which continues to analyse healthcare access as a "one
off" event. The ensuing lack of understanding healthcare behaviour is problematic
in light of the immense burden of premature death especially in low- and middle
income countries. This paper presents an alternative approach. Based on a novel
survey instrument, we analyse original survey data from rural India and China
that contain 119 unique healthcare pathways among 637 respondents. We offer three
applications of how such sequential data can be analysed to enhance our
understanding of people's health behaviour. First, descriptive analysis of
sequential data enables more a comprehensive representation of people's health
behaviours, for example the time spent in various healthcare activities, common
healthcare pathways across different groups, or shifts in healthcare provider
access during a typical illness. Second, by analysing the effect of mobile
technology on healthcare-seeking process characteristics, we demonstrate that
conventional, sequence-insensitive indicators are potentially inconsistent and
misleading approximations when compared to a more precise, sequence-sensitive
measure. Third, we describe how sequential data enable transparent and flexible
evaluations of people's healthcare behaviour. The example of a sequence
insensitive evaluation suggests that household wealth has no statistical link to
an illustrative "ideal" form of public healthcare utilisation. In contrast,
sequence-sensitive evaluations demonstrate that household wealth is associated
with an increased likelihood of bypassing referral processes and approaching
unregulated and costly informal and private practitioners before accessing a
public clinic. Sequential data therefore do not only reveal otherwise neglected
locational idiosyncrasies, but they also yield deeper insights into the drivers
of people's health behaviours compared to a conventional approach to "access to
healthcare."
PMID- 29349204
TI - Validity of a scale of neighbourhood informal social control relevant to pre
schoolers' physical activity: A cross-sectional study.
AB - Childhood physical activity (PA) is important for health across the lifespan.
Time pre-schoolers spend outdoors, which has been associated with more PA, is
likely influenced by parents' perception of neighbourhood informal social control
relevant to pre-schoolers' PA, defined as the willingness of neighbours to
intervene to ensure social order and a safe community environment for young
children's active play. To advance measurement of this construct, we assessed
factorial and construct validities of the PA-related neighbourhood informal
social control scale for parents of pre-schoolers (PANISC-PP). In 2013-2014, Hong
Kong primary caregivers (n=394) of 3-5 year-old children completed a socio
demographic questionnaire, the preliminary version of the PANISC-PP, and self
report measures of theoretical neighbourhood correlates of PA-related
neighbourhood informal social control (perceived signs of physical and social
disorder, community cohesion, perceived stranger danger, risk of unintentional
injury and traffic safety). The fit of the data to an a priori measurement model
of the PANISC-PP was examined using confirmatory factor analyses. As the a priori
model showed inadequate fit to the data, the factor structure was re-specified
based on theoretical considerations. The final measurement models of the PANISC
PP showed acceptable fit to the data and consisted of three correlated latent
factors: "General informal supervision", "Civic engagement for the creation of a
better neighbourhood environment" and "Educating and assisting neighbourhood
children". The internal reliability of the subscales was good (Cronbach's alpha
values 0.82-0.89). Generalised additive mixed models indicated that all subscales
were positively associated with community cohesion and scores on the subscale
"Educating and assisting neighbourhood children" were related in the expected
direction to all indicators of traffic and personal safety, supporting construct
validity of the PANISC-PP. This study suggests that the PANISC-PP is a reliable
and valid instrument for assessing parents' perceived neighbourhood informal
social control related to pre-schoolers' PA.
PMID- 29349203
TI - Neighbourhood socioeconomic status indices and early childhood development.
AB - The developmental health of young children is highly influenced by the
socioeconomic conditions in which they are raised. How to accurately measure
these conditions is a point of debate in the current literature on child
development, health, and social determinants. We have evaluated four existing
indices of socioeconomic status (SES) to determine the most relevant for the
analysis of early childhood development (ECD) in Canada. Following a literature
review of published SES indices which used 2006 Canadian Census data, four
indices were chosen based on their relevance to ECD and the number of citations
in subsequent articles. These were: the Canadian Deprivation Index, the
Socioeconomic Factor Index, the Canadian Marginalization Index and an index
created by the Early Childhood Mapping Project in Alberta, Canada. The indices
were replicated using SES data for 2038 customized geographic neighbourhoods
encompassing 99.9% of the Canadian population, and the relationship of the
indices to ECD was investigated by linking to aggregated data from the Early
Development Instrument (EDI), a teacher-completed questionnaire used to assess
kindergarten children's physical, social, emotional, and cognitive development,
and communication skills. The derived SES indices were compared based on four
criteria: the input variables used, the index structure, the interpretability of
the index and the variance they explained (R2) in the different EDI outcome
measures. In terms of variance explained, material components of the SES indices
(e.g., income, education) consistently showed the strongest association with
children's language and cognitive development. The patterns of association for
the non-material SES components and the other developmental domains of the EDI
were more complex. We discuss the findings in regard to current developments in
the field, and the need for refining empirical and theoretical approaches to
examine associations between different facets of SES contextual factors and
different aspects of ECD outcomes.
PMID- 29349205
TI - Cool? Young people investigate living in cold housing and fuel poverty. A mixed
methods action research study.
AB - Background: Living in cold housing conditions and risk of fuel poverty presents a
range of physiological and psychosocial health risks. Limited research has
specifically investigated the effects of fuel poverty on children and young
people, and even less has been conducted with youth input into the research
process. Methods: The Cool? Study used mixed methods, participatory action
research carried out with youth researchers involved at all stages through
questionnaire design, analysis, qualitative design, e-interviewing and
dissemination of results. This article reports on results of an online survey of
656 adolescents aged 14-16 years completed at 17 schools in New Zealand. Sampling
was based on selecting schools for invitation, with the probability of selection
weighted proportional to school size, within strata defined by climate zone.
Results from a small e-mail interview study of survey respondents who consented
to follow-up are also reported. Results: The study found that almost half of the
survey respondents (47%) felt their home was sometimes cold during the winter; a
further 40% felt their home was often or always cold. More than two thirds of
respondents (70%) had shivered inside at least once during winter. Respondents
were more likely to report key indicators of fuel poverty depending on their self
reported ethnicity, with Maori at increased risk. Living in private rental
housing or state-owned housing also increased risk of fuel poverty compared to
those in owner-occupied dwellings. Participants of email interviews expressed
concern about the widespread problem of cold housing for youth and a desire for
Government intervention. Conclusion: The integrated results confirm that cold
housing and risk of fuel poverty are important problems for young people in New
Zealand. Results contribute to the evidence-base for policy targeting of schemes
such as the Government-sponsored retrofitting of insulation to households with
dependent children.
PMID- 29349206
TI - Dark shadow of the long white cloud: Neighborhood safety is associated with self
rated health and cortisol during pregnancy in Auckland, Aotearoa/New Zealand.
AB - Auckland, Aotearoa/New Zealand is a culturally and ethnically diverse city.
Despite popular global conceptions regarding its utopian nature, the lived
experience for many individuals in Auckland attests to the substantial social,
economic, and health inequalities that exist there. In particular, rapidly rising
home prices constrain housing decisions and force individuals to live in less
desirable neighborhoods, with potential impacts on individual health. One of the
pathways through which adverse neighborhood conditions could impact health is
through alterations in the functioning of the hypothalamic pituitary adrenal
(HPA)-axis, which regulates the physiological stress response. This paper
evaluates the relationship between perceived neighborhood safety, self-rated
health, and cortisol, an end product of HPA-axis activation, among women in late
pregnancy. Pregnant women living in neighborhoods where they were concerned about
safety of their property had poorer self-rated health and elevated morning
cortisol, even after adjusting for maternal age, material deprivation, and
ethnicity. However, fear of personal safety was unrelated to self-rated health
and cortisol. These results suggest that maternal health in pregnancy is
sensitive to perceptions regarding neighborhood safety. Such findings are
important since higher cortisol levels in pregnancy could not only influence
maternal health, but also the health and development of women's children.
PMID- 29349207
TI - Gender career divide and women's disadvantage in depressive symptoms and physical
limitations in France.
AB - This study investigated the relationship between women's disadvantage in mental
health and physical functioning and gender differences in career backgrounds.
Sexual division of labor persists and key career characteristics are
overrepresented in women: low-skilled first job, downward occupational
trajectory, interruptions. These interrelated characteristics are usually linked
to poor health. Their overrepresentation in women may be related to the female
male health gap; however, it may not if overrepresentation transposed into
substantially weaker associations with poor health outcomes. To address this
question, we used the French population survey "Health and Occupational
Trajectories" (2006) and focused on 45-74 year-old individuals who ever worked
(n=7537). Past career characteristics were qualified by retrospective
information. Logistic regressions identified past characteristics related to
current depressive symptoms and physical limitations. Non-linear decomposition
showed whether these characteristics contributed to the gender health gap,
through their different distribution and/or association with health. The
overrepresentation of unskilled first jobs, current and past inactivity and
unemployment in women contributed to their excess depressive symptoms. These
contributions were only slightly reduced by the weaker mental health-relatedness
of current inactivity in women and increased by the stronger relatedness of low
skilled and self-employed first jobs. Overrepresentation of current inactivity,
past interruptions and downward trajectories also contributed positively to
women's excess physical limitations. Gender-specific career backgrounds were
significantly linked to women's disadvantage in mental health and physical
functioning. We need to further explore whether equalization of opportunities,
especially at the early stages and in terms of career continuity, could help to
reduce women's mental and physical health disadvantage.
PMID- 29349208
TI - In sickness and in health: The role of marital partners in cancer survival.
AB - Married cancer patients enjoy a survival advantage, potentially attributable to
better health at diagnosis, earlier contact with health personnel, and/or access
to resources to ensure more optimal treatment. These mechanisms only invoke the
mere presence of a partner, but partners bring varying amounts of resources into
the household. It is likely that also spousal resources contribute to
differentials in survival net of own resources, as gradients in survival by the
latter are well documented. Our aim is to examine the combined roles of own and
spouses' socioeconomic characteristics (SES) and age for cancer survival. Almost
268,000 married patients diagnosed with a first cancer after age 50 during 1975
2007 were identified from the Norwegian Cancer Registry and other national
registers. In a sequence of hazard models, differences in survival by patients'
own education, income and age and the role of spouses' characteristics were
assessed. Furthermore, we also assessed the importance of homogamy/heterogamy
along the same dimensions. Partners' characteristics clearly matter for survival.
The relative survival of patients with highly educated partners, net of their own
education, is significantly higher than that of patients with lesser-educated
partners. Somewhat similar effects are observed for income, net of education. A
less consistent pattern is observed for age, although non-normative heterogamy
patterns in age and income appear to be associated with a survival disadvantage.
The naive perspective of only considering the presence of partners may thus
conceal important differences in cancer survival. Health personnel may take
advantage of such knowledge in interactions with patients and their families, and
gather information on resources in immediate networks that may impact prognosis
favorable and/or unfavorable and help patients utilize these resources to improve
prognosis.
PMID- 29349209
TI - Immigration concern and the white/non-white difference in smoking: Group position
theory and health.
AB - National data indicate that U.S. whites have a higher prevalence of smoking
compared to non-whites. Group position theory and public opinion data suggest
racial differences in immigration concern. This study examines whether
immigration concern mediates the racial difference in smoking. Drawing on the
2012 General Social Survey, the 2012 American National Election Study, and the
2006 Portraits of American Life Study, immigration concern was associated with
smoking, controlling for covariates across all three nationally representative
surveys. Mediation analysis indicated that immigration concern partially mediated
the higher odds of smoking among whites across all surveys. Immigration concern
also presents a possible explanation for the healthy immigrant advantage and
Hispanic paradox as they pertain to smoking differences.
PMID- 29349210
TI - Early-life conditions and child development: Evidence from a violent conflict.
AB - This paper investigates how the exposure to violent conflicts in utero and in
early and late childhood affect human capital formation. I focus on a wide range
of child development outcomes, including novel cognitive and non-cognitive
indicators. Using monthly and municipality-level variation in the timing and
severity of massacres in Colombia from 1999 to 2007, I show that children exposed
to terrorist attacks in utero and in childhood achieve lower height-for-age (0.09
SD) and cognitive outcomes (PPVT falls by 0.18SD and math reasoning and general
knowledge fall by 0.16SD), and that these results are robust to controlling for
mother fixed-effects. The timing of these exposures matters and differs by type
of skill. In terms of parental investments, I find some evidence that parents
reinforce the negative effects of violence by increasing their frequency of
physical aggression.
PMID- 29349211
TI - Who votes for public health? U.S. senator characteristics associated with voting
in concordance with public health policy recommendations (1998-2013).
AB - Background: The voting behaviors of elected officials shape the public's health.
Little is known, however, about the characteristics of elected officials who vote
in concordance with public health policy recommendations. This article presents
the results of study conducted with the aims of: 1) testing the hypothesis that
US Democrat Senators vote in concordance with American Public Health Association
(APHA) policy recommendations more frequently than US Republican Senators, 2)
identifying US Senator characteristics independently associated with voting in
concordance with APHA, and 3) assessing trends in APHA voting concordance by
political party. Methods: We created a legislative dataset of 1434 votes cast on
111 legislative proposals by 184 US Senators during the years 1998 through 2013.
Mixed effects linear regression models were used to estimate the independent
contributions of political party, gender, geographic region, and year effects to
annual APHA voting concordance. Votes were nested within Senators who were nested
within States to account for non-independence and models considered potential for
time and spatial patterns in the data. Results: Adjusting for covariates and
accounting for serial and spatial autocorrelation, Democrats averaged 59.1
percentage points higher in annual APHA voting concordance than Republicans (95%
CI: 55.5, 62.7), females averaged 7.1 percentage points higher than males (95%
CI: 1.9, 12.3), and Northeastern Senators averaged 16.1 percentage points higher
than Southern Senators (95% CI: 9.1, 23.1). Conclusions: Elected official's
political party affiliation, gender, and geographic region are independently
associated with public health voting decisions and should be considered when
targeting and tailoring science-based policy dissemination strategies.
PMID- 29349212
TI - Place, health, and community attachment: Is community capacity associated with
self-rated health at the individual level?
AB - Community-level interventions dominate contemporary public health responses to
health inequalities as a lack of political will has discouraged action at a
structural level. Health promoters commonly leverage community capacity to
achieve programme goals, yet the health implications of low community capacity
are unknown. In this study, we analyse perceptions of community capacity at the
individual-level to explore how place-based understandings of identity and
connectedness are associated with self-rated health. We examine associations
between individual community capacity, self-rated health and income using a cross
sectional survey that was disseminated to 303 residents of four small
(populations 1500-2000) New Zealand towns. Evidence indicating a relationship
between individual community capacity and self-reported health was unconvincing
once the effects of income were incorporated. That is, people who rated their
community's capacity higher did not have better self-rated health. Much stronger
evidence supported the relationship between income and both higher individual
community capacity and higher self-rated health. We conclude that individual
community capacity may mediate the positive association between income and
health, however, overall we find no evidence suggesting that intervening to
enhance individual community capacity is likely to improve health outcomes.
PMID- 29349213
TI - Socioeconomic inequality in morbid obesity with body mass index more than 40
kg/m2 in the United States and England.
AB - Introduction: This study evaluated socioeconomic inequality in morbid obesity
(body mass index, BMI >=40 kg/m2) through an analysis of population health survey
data in the United States (US) and England (UK). Methods: We analysed data for
the National Health and Nutrition Examination Survey and the Health Survey for
England for 2011 to 2014. Age-adjusted odds ratios (AOR) were used to evaluate
income- and education-inequality. Results: There were 26,898 eligible UK and
10,628 US participants. Morbid obesity was more frequent in women than men, and
higher in the US than the UK (men: US, 4.8%; UK, 1.7%; women US, 9.6%; UK, 3.7%).
In the UK, morbid obesity showed graded income-inequality in both genders (AOR,
for lowest income quintile: men, 1.83, 95% confidence interval 1.16 to 2.88;
women, 2.18, 1.55 to 3.07), as well as education-inequality (AOR for no school
qualifications, men 2.57, 1.64 to 4.02; women, 2.18, 1.55 to 3.07). In the US,
morbid obesity showed a consistent gradient only for income in women (AOR for
lowest income quintile 1.97, 1.19 to 3.25). When compared with all other US
groups, having college education (AOR, men, 0.56, 0.29 to 1.08; women, 0.36, 0.22
to 0.60) or household income >=$75 000 (AOR, men 0.52, 0.27 to 0.98; women, 0.51,
0.33 to 0.80) appeared to protect against morbid obesity. Conclusions: Morbid
obesity is associated with lower socioeconomic status in men and women in the UK.
In the US, morbid obesity was twice as prevalent, but less strongly associated
with socioeconomic status, suggesting that morbid obesity may now have spread to
all but the highest socioeconomic groups.
PMID- 29349214
TI - Performance-based financing to increase utilization of maternal health services:
Evidence from Burkina Faso.
AB - Performance-based financing (PBF) programs are increasingly implemented in low
and middle-income countries to improve health service quality and utilization. In
April 2011, a PBF pilot program was launched in Boulsa, Leo and Titao districts
in Burkina Faso with the objective of increasing the provision and quality of
maternal health services. We evaluate the impact of this program using facility
level administrative data from the national health management information system
(HMIS). Primary outcomes were the number of antenatal care visits, the proportion
of antenatal care visits that occurred during the first trimester of pregnancy,
the number of institutional deliveries and the number of postnatal care visits.
To assess program impact we use a difference-in-differences approach, comparing
changes in health service provision post-introduction with changes in matched
comparison areas. All models were estimated using ordinary least squares (OLS)
regression models with standard errors clustered at the facility level. On
average, PBF facilities had 2.3 more antenatal care visits (95% CI [0.446
4.225]), 2.1 more deliveries (95% CI [0.034-4.069]) and 9.5 more postnatal care
visits (95% CI [6.099, 12.903]) each month after the introduction of PBF.
Compared to the service provision levels prior to the interventions, this implies
a relative increase of 27.7 percent for ANC, of 9.2 percent for deliveries, and
of 118.7 percent for postnatal care. Given the positive results observed during
the pre-pilot period and the limited resources available in the health sector,
the PBF program in Burkina Faso may be a low-cost, high impact intervention to
improve maternal and child health.
PMID- 29349215
TI - Public health and the economy could be served by reallocating medical
expenditures to social programs.
AB - As much as 30% of US health care spending in the United States does not improve
individual or population health. To a large extent this excess spending results
from prices that are too high and from administrative waste. In the public
sector, and particularly at the state level, where budget constraints are severe
and reluctance to raise taxes high, this spending crowds out social, educational,
and public-health investments. Over time, as spending on medical care increases,
spending on improvements to the social determinants of health are starved. In
California the fraction of General Fund expenditures spent on public health and
social programs fell from 34.8% in fiscal year 1990 to 21.4% in fiscal year 2014,
while health care increased from 14.1% to 21.3%. In spending more on healthcare
and less on other efforts to improve health and health determinants, the state is
missing important opportunities for health-promoting interventions with a strong
financial return. Reallocating ineffective medical expenditures to proven and
cost-effective public health and social programs would not be easy, but
recognizing its potential for improving the public's health while saving
taxpayers billions of dollars might provide political cover to those willing to
engage in genuine reform. National estimates of the percent of medical spending
that does not improve health suggest that approximately $5 billion of
California's public budget for medical spending has no positive effect on health.
Up to 10,500 premature deaths could be prevented annually by reallocating this
portion of medical spending to public health. Alternatively, the same expenditure
could help an additional 418,000 high school students to graduate.
PMID- 29349216
TI - Family of origin and educational inequalities in mortality: Results from 1.7
million Swedish siblings.
AB - Circumstances in the family of origin have short- and long-term consequences for
people's health. Family background also influences educational achievements -
achievements that are clearly linked to various health outcomes. Utilizing
population register data, we compared Swedish siblings with different levels of
education (1,732,119 individuals within 662,095 sibships) born between 1934 and
1959 and followed their death records until the end of 2012 (167,932 deaths). The
educational gradient in all-cause mortality was lower within sibships than in the
population as a whole, an attenuation that was strongest at younger ages (< 50
years of age) and for those with a working class or farmer background. There was
substantial variation across different causes of death with clear reductions in
educational inequalities in, e.g., lung cancer and diabetes, when introducing
shared family factors, which may indicate that part of the association can be
ascribed to circumstances that siblings have in common. In contrast, educational
inequalities in suicide and, for women, other mental disorders increased when
adjusting for factors shared by siblings. The vast variation in the role of
childhood conditions for the education-mortality association may help us to
further understand the interplay between family background, education, and
mortality. The increase in the education gradient in suicide when siblings are
compared may point towards individually oriented explanations ('non-shared
environment'), perhaps particularly in mental disorders, while shared family
factors primarily seem to play a more important role in diseases in which health
behaviors are most significant.
PMID- 29349217
TI - The Mothers on Respect (MOR) index: measuring quality, safety, and human rights
in childbirth.
AB - Background: Abuse of human rights in childbirth are documented in low, middle and
high resource countries. A systematic review across 34 countries by the WHO
Research Group on the Treatment of Women During Childbirth concluded that there
is no consensus at a global level on how disrespectful maternity care is
measured. In British Columbia, a community-led participatory action research team
developed a survey tool that assesses women's experiences with maternity care,
including disrespect and discrimination. Methods: A cross-sectional survey was
completed by women of childbearing age from diverse communities across British
Columbia. Several items (31/130) assessed characteristics of their communication
with care providers. We assessed the psychometric properties of two versions of a
scale (7 and 14 items), among women who described experiences with a single
maternity provider (n=2514 experiences among 1672 women). We also calculated the
proportion and selected characteristics of women who scored in the bottom 10th
percentile (those who experienced the least respectful care). Results: To
demonstrate replicability, we report psychometric results separately for three
samples of women (S1 and S2) (n=2271), (S3, n=1613). Analysis of item-to-total
correlations and factor loadings indicated a single construct 14-item scale,
which we named the Mothers on Respect index (MORi). Items in MORi assess the
nature of respectful patient-provider interactions and their impact on a person's
sense of comfort, behavior, and perceptions of racism or discrimination. The
scale exhibited good internal consistency reliability. MORi- scores among these
samples differed by socio-demographic profile, health status, experience with
interventions and mode of birth, planned and actual place of birth, and type of
provider. Conclusion: The MOR index is a reliable, patient-informed quality and
safety indicator that can be applied across jurisdictions to assess the nature of
provider-patient relationships, and access to person-centered maternity care.
PMID- 29349218
TI - Comparing methods of targeting obesity interventions in populations: An agent
based simulation.
AB - Social networks as well as neighborhood environments have been shown to effect
obesity-related behaviors including energy intake and physical activity.
Accordingly, harnessing social networks to improve targeting of obesity
interventions may be promising to the extent this leads to social multiplier
effects and wider diffusion of intervention impact on populations. However, the
literature evaluating network-based interventions has been inconsistent.
Computational methods like agent-based models (ABM) provide researchers with
tools to experiment in a simulated environment. We develop an ABM to compare
conventional targeting methods (random selection, based on individual obesity
risk, and vulnerable areas) with network-based targeting methods. We adapt a
previously published and validated model of network diffusion of obesity-related
behavior. We then build social networks among agents using a more realistic
approach. We calibrate our model first against national-level data. Our results
show that network-based targeting may lead to greater population impact. We also
present a new targeting method that outperforms other methods in terms of
intervention effectiveness at the population level.
PMID- 29349219
TI - Drug involvement in fatal overdoses.
AB - Death certificate data from the Multiple Cause of Death (MCOD) files were
analyzed to better understand the drug categories most responsible for the
increase in fatal overdoses occurring between 1999 and 2014. Statistical
adjustment methods were used to account for the understatement in reported drug
involvement occurring because death certificates frequently do not specify which
drugs were involved in the deaths. The frequency of combination drug use
introduced additional uncertainty and so a distinction was made between any
versus exclusive drug involvement. Many results were sensitive to the starting
and ending years chosen for examination. Opioid analgesics played a major role in
the increased drug deaths for analysis windows starting in 1999 but other drugs,
particularly heroin, became more significant for recent time periods. Combination
drug use was important for all time periods and needs to be accounted for when
designing policies to slow or reverse the increase in overdose deaths.
PMID- 29349220
TI - Adult mortality in sub-saharan Africa, Zambia: Where do adults die?
AB - Place of death remains an issue of growing interest and debate among scholars as
an indicator of quality of end-of-life care in developed countries. In sub
Saharan Africa, however, variations in place of death may suggest inequalities in
access to and the utilization of health care services that should be addressed by
public health interventions. Limited research exists on factors associated with
place of death in sub-Saharan Africa. The study examines factors associated with
the place of death among Zambian adults aged 15-59 years using the 2010-2012
sample vital registration with verbal autopsy survey (SAVVY) data, descriptive
statistics and multivariate logistic regression analysis. Results show that more
than half of the adult deaths occurred in a health facility and two-fifths died
at home. Higher educational attainment, urban versus rural residence, and being
of female gender were significant predictors of the place of death. Improvement
in educational attainment and investment in rural health facilities and the
health care system as a whole may improve access and utilization of health
services among adults.
PMID- 29349221
TI - Women at war: The crucible of Vietnam.
AB - Relatively little has been written about the military women who served in
Vietnam, and there is virtually no literature on deployed civilian women (non
military). We examined the experiences of 1285 American women, military and
civilian, who served in Vietnam during the war and responded to a mail survey
conducted approximately 25 years later in which they were asked to report and
reflect upon their experiences and social and health histories. We compare
civilian women, primarily American Red Cross workers, to military women
stratified by length of service, describe their demographic characteristics and
warzone experiences (including working conditions, exposure to casualties and
sexual harassment), and their homecoming following Vietnam. We assess current
health and well-being and also compare the sample to age- and temporally
comparable women in the General Social Survey (GSS), with which our survey shared
some measures. Short-term (<10 years) military service women (28%) were more
likely to report their Vietnam experience as "highly stressful" than were career
(>20 years; 12%) and civilian women (13%). Additional differences regarding
warzone experiences, homecoming support, and health outcomes were found among
groups. All military and civilian women who served in Vietnam were less likely to
have married or have had children than women from the general population, chi2
(8) = 643.72, p < .001. Career military women were happier than women in the
general population (48% were "very happy", as compared to 38%). Civilian women
who served in Vietnam reported better health than women in the other groups.
Regression analyses indicated that long-term physical health was mainly
influenced by demographic characteristics, and that mental health and PTSD
symptoms were influenced by warzone and homecoming experiences. Overall, this
paper provides insight into the experiences of the understudied women who served
in Vietnam, and sheds light on subgroup differences within the sample.
PMID- 29349222
TI - A comprehensive analysis of the mortality experience of hispanic subgroups in the
United States: Variation by age, country of origin, and nativity.
AB - Although those identifying as "Hispanic or Latino" experience lower adult
mortality than the more socioeconomically advantaged non-Hispanic white
population, the ethnic category Hispanic conceals variation by country of origin,
nativity, age, and immigration experience. The current analysis examines adult
mortality differentials among 12 Hispanic subgroups by region of origin and
nativity, and non-Hispanic whites, adjusting for socioeconomic and demographic
characteristics. We use the National Health Interview Survey Linked Mortality
Files pooled 1990-2009 to obtain sufficient sample of each subgroup to calculate
mortality estimates by sex and age group (25-64, 65+). Among adults aged 65 and
over, all foreign born subgroups have an advantage over non-Hispanic whites, and
many USB subgroups exhibit an advantage in the adjusted model. Foreign-born
Dominicans, Central/South Americans, and other Hispanics exhibit consistent
advantages across models for both men and women, aged 25-64 and 65 and over, and
both unadjusted and adjusted for socioeconomic covariates. Both US-born and
foreign-born Mexicans between ages 25 and 64 have mortality disadvantaged
relative to non-Hispanic whites, while older Mexicans exhibit clear advantages.
Our results complicate the traditional formulation of the Hispanic Paradox and
cast doubt on the singularity of the mortality experience of those of Hispanic
origin.
PMID- 29349223
TI - Social participation and self-rated psychological health: A longitudinal study on
BHPS.
AB - Although social capital has been hypothesized to have positive influence on
psychological health, a relationship between social capital dimensions and
psychological wellbeing has rarely been found. This longitudinal study
investigates the relationship between social participation in associations and
self-rated psychological health. The paper uses five waves of the British
Household Panel Survey (BHPS) from 1991 to 1995 (unbalanced panel N=45,761).
Ordered logit fixed effect methods were used to study the longitudinal link
between structural social capital (being a member, active, and both a member and
active in associations) and self-rated psychological health assessed by single
items of the General Health Questionnaire (GHQ-12) controlling for age, marital
status, household size, number of children, education, income, economic status,
number of visits to the GP and health problems. The paper shows that being only a
member and only active in associations has no statistical relationship with
almost all the items of the GHQ-12. Instead, being both a member and active in
associations is linked to all "positive" items of self-rated psychological health
and to two main "negative" items of psychological wellbeing. These findings
highlight the protective role of being both a member and active in associations
against poor psychological health outcomes.
PMID- 29349224
TI - A couple-level analysis of participation in physical activity during
unemployment.
AB - There is a well-documented negative correlation between unemployment and health.
Yet, little research has examined how unemployment relates to participation in
physical activity, and few researchers have considered how an individual's
unemployment may affect the health of their spouse or partner. The purpose of
this study is to answer three questions: 1. Is one's own unemployment associated
with changes in physical activity participation? 2. Is one's partner's
unemployment associated with changes in physical activity participation? 3. Do
changes in physical activity behaviors associated with unemployment differ by
gender? This study uses nationally representative, longitudinal data on couples
in the United States, covering the period 1999-2013. These data, obtained from
the Panel Study of Income Dynamics, are used to estimate fixed-effects models of
the relationships between one's own, and one's partner's, unemployment and
participation in physical activity. I find that for men unemployment is not
associated with changes in physical activity time. For women, own unemployment is
associated with increases in physical activity, whereas a partner's unemployment
is associated with decreases in physical activity. I argue that unemployed women,
unlike men, are able to take advantage of the increased availability of time
through reduced labor supply to invest in their health during unemployment, which
could have positive long-run consequences. Results suggest the importance of
studying unemployment and health at the household level and suggest a need for
further investigation into gender differences in unemployment and health.
PMID- 29349225
TI - Intergenerational differences in smoking among West Indian, Haitian, Latin
American, and African blacks in the United States.
AB - Due in large part to increased migration from Africa and the Caribbean, black
immigrants and their descendants are drastically changing the contours of health
disparities among blacks in the United States. While prior studies have examined
health variation among black immigrants by region of birth, few have explored the
degree of variation in health behaviors, particularly smoking patterns, among
first- and second- generation black immigrants by ancestral heritage. Using data
from the 1995-2011 waves of the Tobacco Use Supplements of the Current Population
Survey (TUS-CPS), we examine variation in current smoking status among first-,
second-, and third/higher- generation black immigrants. Specifically, we
investigate these differences among all black immigrants and then provide
separate analyses for individuals with ancestry from the English-speaking
Caribbean (West Indies), Haiti, Latin America, and Africa-the primary sending
regions of black immigrants to the United States. We also explore differences in
smoking behavior by gender. The results show that, relative to third/higher
generation blacks, first-generation black immigrants are less likely to report
being current smokers. Within the first-generation, immigrants who migrated after
age 13 have a lower probability of smoking relative to those who migrated at or
under age 13. Disparities in smoking prevalence among the first-generation by age
at migration are largest among black immigrants from Latin America. The results
also suggest that second-generation immigrants with two foreign-born parents are
generally less likely to smoke than the third/higher generation. We find no
statistically significant difference in smoking between second-generation
immigrants with mixed nativity parents and the third or higher generation. Among
individuals with West Indian, Haitian, Latin American, and African ancestry, the
probability of being a current smoker increases with each successive generation.
The intergenerational increase in smoking, however, is slower among individuals
with African ancestry. Finally, with few exceptions, our results suggest that
intergenerational gaps in smoking behavior are larger among women compared to
men. As additional sources of data for this population become available,
researchers should investigate which ancestral subgroups are driving the
favorable smoking patterns for the African origin population.
PMID- 29349226
TI - Seeking relief: Bankruptcy and health outcomes of adult women.
AB - This study examined the impact of declaring consumer bankruptcy on the physical
and mental health of adult women and if outcomes differed depending on whether
the filer received automatic debt discharge under Chapter 7 compared to a debt
repayment plan with Chapter 13. Sample data consisted of women from the NLSY79
cohort who completed the age 40 and 50 health modules as of the most recent wave.
Results indicated a negative effect of bankruptcy on self-assessed health,
whereas prior health history explained its negative relationship with depressive
symptoms. Debt liquidation under Chapter 7 was associated with poor physical
health relative to those who did not file and with depressive symptoms relative
to Chapter 13 repayment plan filers. Poor health is an unintended consequence for
women who seek financial relief through bankruptcy.
PMID- 29349227
TI - Conceptualizing, measuring and evaluating constructs of the adolescent
neighbourhood social environment: A systematic review.
PMID- 29349228
TI - Children's migration and lifestyle-related chronic disease among older parents
'left behind' in india.
AB - Lifestyle-related chronic diseases such as cardiovascular diseases and diabetes
are now the leading causes of death and disability in India. Interestingly, those
Indian states with the highest prevalence of lifestyle-related chronic disease
among older adults are also found to have the highest rates of international or
internal out-migration. This paper investigates the association between having
migrant (adult) children and older parents' lifestyle-related chronic disease in
India. Bi-variate and multivariate analysis are conducted using data from a
representative sample of 9507 adults aged 60 and older in seven Indian states
from the UNFPA project 'Building Knowledge Base on Ageing in India'. The results
show that for any of the diagnosed conditions of hypertension, diabetes and heart
disease, the prevalence among older people with a migrant son is higher than
among those without. More specifically, the odds ratio of reporting a lifestyle
related chronic disease is higher among older adults with at least one adult son
living in another district, State or outside India than those with their children
living closer. This study contributes empirical evidence to the academic and
policy debate about the consequences of globalization and urbanization for older
people's health status generally, and particularly their risk for reporting
chronic diseases that relate to changes in their lifestyle.
PMID- 29349229
TI - Does gender inequity increase men's mortality risk in the United States? A
multilevel analysis of data from the National Longitudinal Mortality Study.
AB - A number of theoretical approaches suggest that gender inequity may give rise to
health risks for men. This study undertook a multilevel analysis to ascertain if
state-level measures of gender inequity are predictors of men's mortality in the
United States. Data for the analysis were taken primarily from the National
Longitudinal Mortality Study, which is based on a random sample of the non
institutionalised population. The full data set included 174,703 individuals
nested within 50 states and had a six-year follow-up for mortality. Gender
inequity was measured by nine variables: higher education, reproductive rights,
abortion provider access, elected office, management, business ownership, labour
force participation, earnings and relative poverty. Covariates at the individual
level were age, income, education, race/ethnicity, marital status and employment
status. Covariates at the state level were income inequality and per capita gross
domestic product. The results of logistic multilevel modelling showed a number of
measures of state-level gender inequity were significantly associated with men's
mortality. In all of these cases greater gender inequity was associated with an
increased mortality risk. In fully adjusted models for all-age adult men the
elected office (OR 1.05 95% CI 1.01-1.09), business ownership (OR 1.04 95% CI
1.01-1.08), earnings (OR 1.04 95% CI 1.01-1.08) and relative poverty (OR 1.07 95%
CI 1.03-1.10) measures all showed statistically significant effects for each 1
standard deviation increase in the gender inequity z-score. Similar effects were
seen for working-age men. In older men (65+ years) only the earnings and relative
poverty measures were statistically significant. This study provides evidence
that gender inequity may increase men's health risks. The effect sizes while
small are large enough across the range of gender inequity identified to have
important population health implications.
PMID- 29349230
TI - Education, race/ethnicity, and multimorbidity among adults aged 30-64 in the
National Health Interview Survey.
AB - Background: Demographic risk factors for multimorbidity have been identified in
numerous population-based studies of older adults; however, there is less data on
younger populations, despite the fact that approximately 24% of US adults age 18+
have multimorbidity. Understanding multimorbidity earlier in the life course is
critical because of the increased likelihood of long-term disability and loss of
productivity associated with chronic disease progression. Objective: To examine
the associations of education and race/ethnicity with mutimorbidity among adults
aged 30-64 using cross-sectional data from the 2002-2014 National Health
Interview Surveys. Design: Multimorbidity was defined as having at least 2 of 9
self-reported health conditions. Educational attainment was categorized as less
than high school (HS), completed HS or some college, and bachelor's degree or
higher. Logistic regression models of multimorbidity controlled for time since
last doctor's visit, demographic and socioeconomic measures. Results: Compared to
having a bachelor's degree or higher, completing less than HS (OR=1.58, 95% CI =
1.50-1.66) or HS/some college (OR=1.32, 95% CI = 1.27-1.37) were both associated
with increased odds of multimorbidity net of all included covariates. Non
Hispanic Blacks had greater odds of multimorbidity (OR=1.07, 95% CI = 1.02-1.11)
compared to Non-Hispanic Whites with comparable characteristics. Conclusions:
Epidemiologic and demographic research on the burden of multimorbidity among non
elderly adults is limited, but warrants renewed attention given the potential for
long-term loss of quality of life, productivity, and well-being for non-elderly
adults. Reducing multimorbidity through health promotion efforts across the
socioeconomic spectrum and earlier in the life course will be a requirement to
age successfully and support overall well-being in the aging US population.
PMID- 29349231
TI - Improving population health by reducing poverty: New York's Earned Income Tax
Credit.
AB - Despite the established relationship between adverse health outcomes and low
socioeconomic status, researchers rarely test the link between health
improvements and poverty-alleviating economic policies. New research, however,
links individual-level health improvements to the Earned Income Tax Credit
(EITC), a broad-based income support policy. We build on these findings by
examining whether the EITC has ecological, neighborhood-level health effects. We
use a difference-in-difference analysis to measure child health outcomes in 90
low- and middle- income neighborhoods before and after the expansion of New York
State and New York City's EITC policy between 1997-2010. Our study takes
advantage of the relatively exogenous source of income variation supplied by the
EITC-legislative changes to EITC policy parameters. This feature minimizes the
endogeneity problem in studying the relationship between income and health. Our
estimates link a 15-percentage-point increase in EITC benefit rates to a 0.45
percentage-point reduction in the low birthweight rate. We do not observe any
measurable link between EITC benefits and prenatal health or asthma-related
pediatric hospitalization. The magnitude of the EITC's impact on low birthweight
rates suggests ecological effects, and an additional channel through which anti
poverty measures can serve as public health interventions.
PMID- 29349232
TI - Health and well-being at work: The key role of supervisor support.
AB - This study aims to explore whether and in what way social support from different
sources and domains makes an additional or different and independent contribution
to various health and work-related outcomes. Cross-sectional data were used from
an employee survey among the workforces of four service companies from different
industries in Switzerland. The study sample covered 5,877 employees of working
age. The lack of social support from a spouse, relatives, friends, direct
supervisors, closest colleagues at work and other co-workers in case of problems
at work and at home were assessed and studied individually and jointly as risk
factors with respect to a total number of eight outcomes. Health-related outcomes
covered poor self-rated health, musculoskeletal disorders, stress feelings and
burnout symptoms. Work-related outcomes included feeling overwhelmed at work,
difficulty with switching off after work, job dissatisfaction and intention to
turnover. Social support from multiple sources in contrast to only individual
sources in both life domains was found to be more frequent in women than in men
and proved to be most protective and beneficial with regard to health and well
being at work. However, after mutual adjustment of all single sources of social
support from both domains, a lack of supervisor support turned out to be the only
or the strongest of the few remaining support measures and statistically
significant risk factors for the studied outcomes throughout and by far. Being
unable to count on the support of a direct supervisor in case of problems at work
and even at home was shown to involve a substantially increased risk of poor
health and work-related outcomes (aOR = up to 3.8). Multiple sources of social
support, and particularly supervisor support, seem to be important resources of
health and well-being at work and need to be considered as key factors in
workplace health promotion.
PMID- 29349233
TI - Associations between household educational attainment and adolescent positive
mental health in Canada.
AB - Investigating the determinants of positive mental health, as opposed to focusing
on mental illness, is a new research direction with important implications for
population health promotion. Past research suggests that mental health develops
in early childhood and that social factors including highest household
educational attainment may play an important role. The current study examined the
association between household educational attainment and adolescent self-reported
positive mental health in a nationally representative Canadian sample using data
from the 2011-12 Canadian Community Health Survey. The sample included 10,091
adolescents aged 12 to19 living at home with at least one parent. Household
educational attainment was obtained from a Statistics Canada derived variable
documenting the highest level of education in the household. Adolescent positive
mental health was assessed using the Mental Health Continuum scale. Multivariable
logistic regression analyses showed that after adjusting for household income,
single parent status, and household size, adolescents had lower odds of
experiencing positive mental health in households in which attempted but not
completed post-secondary was the highest education level compared to completed
post-secondary education (OR = 0.64, 95% CI = 0.44, 0.95). This association was
strongest in adolescents aged 12 to14 (OR = 0.43, 95% CI = 0.21, 0.84) and
females (OR = 0.50, 95% CI = 0.29, 0.88). Contrary to expectations, we did not
find an incremental increasing association between adolescent positive mental
health and household educational attainment. Instead, results suggested that
common underlying factors may have contributed both to uncompleted post-secondary
education in the household and adolescents' diminished positive mental health.
PMID- 29349234
TI - Adult health returns to education by key childhood social and economic
indicators: Results from representative European data.
AB - In the United States, associations between attained education and adult health
typically are larger for those from disadvantaged childhood backgrounds. However,
it remains unclear how specific key childhood indicators contribute to these
adult health patterns, especially outside the United States. Drawing on the 2014
European Social Survey (20 countries; N=31544), we investigate the key childhood
and adolescent indicators of parental education, childhood financial strain, and
any serious household conflict growing up, given how these early exposures are
known to correlate strongly with both educational attainment and adult health. In
regressions with country fixed effects, we find across Europe that higher levels
of education are more strongly linked to lessened adult depressive symptoms when
childhood disadvantage is present in terms of lower levels of parental education
or higher childhood financial strain specifically. However, adjusted predictions
reveal that childhood financial strain contributes to this heterogeneity in
educational returns far more strongly than parental education. For self-rated
health, only childhood financial strain enhances estimated educational health
benefits when considering all key childhood social and economic factors jointly.
Similarly, childhood financial strain in particular enhances educational
protection against overall rates of disease in adulthood. Overall, our findings
support prior work on United States data revealing higher educational health
returns given childhood disadvantage. At the same time, our findings across three
distinct adult health indicators suggest the particular importance of childhood
financial strain to understanding heterogeneity in educational health returns.
PMID- 29349235
TI - Social pathways to health: On the mediating role of the social network in the
relation between socio-economic position and health.
AB - Good health is one of the key qualities of life, but opportunities to be and
remain healthy are unequally distributed across socio-economic groups. The
beneficial health effects of the social network are well known. However, research
on the social network as potential mediator in the pathway from socio-economic
position (SEP) to health is scarce, while there are good reasons to expect a
socio-economical patterning of networks. We aim to contribute to our
understanding of socio-economic inequalities in health by examining the mediating
role of structural and functional characteristics of the social network in the
SEP-health relationship. Data were from the second wave of the Norwegian study on
the life course, aging and generation study (NorLAG) and comprised 4534 men and
4690 women aged between 40 and 81. We applied multiple mediation models to
evaluate the relative importance of each network characteristic, and multiple
group analysis to examine differences between middle-aged and older men and
women. Our results indicated a clear socio-economical patterning of the social
network for men and women. People with higher SEP had social networks that better
protect against loneliness, which in turn lead to better health outcomes. The
explained variance in health in older people by the social network and SEP was
only half of the explained variance observed in middle-aged people, suggesting
that other factors than SEP were more important for health when people age. We
conclude that it is the function of the network, rather than the structure, that
counts for health.
PMID- 29349236
TI - The prevalence and correlates of suicidal behaviours (ideation, plan and attempt)
among adolescents in senior high schools in Ghana.
AB - Suicide is recognised as the third leading cause of death among adolescents
globally. There is however limited data on the prevalence and factors associated
with suicide particularly in Ghana. To explore the prevalence and risk and
protective factors associated with suicide in Ghana, a nationwide Global School
based Student Health Survey data collected among senior high school adolescents
in Ghana was used. The prevalence of suicidal behaviours was 18.2%, 22.5% and
22.2% for suicidal ideation, suicidal plan and suicidal attempt respectively. In
the final analysis, anxiety increases the odds of suicidal behaviour, even after
controlling for other variables. Loneliness increases the odds of suicidal
behaviour but after adjusting for other factors the odds remained for only
suicidal plan. Being bullied, physically attacked, involved in a physical fight
and food insecurity remained risk factors for suicidal behaviour (i.e. ideation,
plan and attempt) after adjusting for other factors. Truancy was found as a risk
factor for both suicidal ideation and plans but such effect diminished for
suicidal plan after adjusting for other variables. Increasing number of close
friends remained a risk factor for both suicidal plan and attempt but such effect
diminished for suicidal ideation after adjusting for other variables. Parental
understanding of adolescents' problems and worries remained a significant
protective factor for all the indices of suicidal behaviour after adjusting for
other variables. Parental respect for privacy was protective of suicidal attempt
but was not significant after adjusting for other variables. Early identification
and intervention for at-risk adolescents in senior high schools, for example
those experiencing different forms of physical abuse, drug and substance use and
hunger can potentially reduce the prevalence of suicide among this population in
Ghana.
PMID- 29349237
TI - Social capital and pet ownership - A tale of four cities.
AB - *Pet ownership is significantly associated with higher levels of social
capital.*Social capital was associated with pet ownership in the U.S. and
Australia.*Results are not confined to dog owners nor dog walkers.*Pets are an
under-recognized conduit for building social capital.
PMID- 29349238
TI - Engagement with health care providers as a mediator between social capital and
quality of life among a sample of people living with HIV in the United States:
Path-analysis.
AB - Background: Social capital is "features of social organizations-networks, norms,
and as trust that facilitate coordination and cooperation for mutual benefit".
People with high social capital have lower mortality and better health outcomes.
Although utilization of social networks has grown, social capital continues to be
a complex concept in relation to health promotion. This study examined 1)
associations between social capital and quality of life (QoL), 2) factors of
social capital leading to higher QoL among people living with HIV (PLWH), 3) role
of health care providers (HCP) as a mediator between social capital and QoL.
Methods: This is a secondary analysis of the International Nursing HIV Network
for HIV/AIDS Research. This cross-sectional study included 1673 PLWH from 11
research sites in the United States in 2010. Using path analysis, we examined the
independent effect of social capital on QoL, and the mediating effect of PLWH
engagement with HCP. Results: The majority of participants were male (71.2%), and
45.7% were African American. Eighty-nine percent of the participants were on
antiretroviral therapy. Social capital consisted of three factors - social
connection, tolerance toward diversity, and community participation - explaining
87% of variance of social capital. Path analysis (RMSEA = 0, CFI = 1) found that
social connection, followed by tolerance toward diversity, were the principal
domain of social capital leading to better QoL (std. beta = 0.50, std. error =
0.64, p<.05). Social capital was positively associated with QoL (p<.05). About
11% of the protective effect of social capital on QoL was mediated by engagement
with HCP (p<.05). Conclusions: This study emphasizes importance of social
connections and mediating role of HCP in improving QoL for PLWH. To develop
social capital effectively, interventions should focus on strengthening PLWH's
social connections and engagement to HCP.
PMID- 29349239
TI - The household food insecurity gradient and potential reductions in adverse
population mental health outcomes in Canadian adults.
AB - Purpose: Household food insecurity is related to poor mental health. This study
examines whether the level of household food insecurity is associated with a
gradient in the risk of reporting six adverse mental health outcomes. This study
further quantifies the mental health impact if severe food insecurity, the
extreme of the risk continuum, were eliminated in Canada. Methods: Using a pooled
sample of the Canadian Community Health Survey (N = 302,683), we examined the
relationship between level of food insecurity, in adults 18-64 years, and
reporting six adverse mental health outcomes. We conducted a probit analysis
adjusted for multi-variable models, to calculate the reduction in the odds of
reporting mental health outcomes that might accrue from the elimination of severe
food insecurity. Results: Controlling for various demographic and socioeconomic
covariates, a food insecurity gradient was found in six mental health outcomes.
We calculated that a decrease between 8.1% and 16.0% in the reporting of these
mental health outcomes would accrue if those who are currently severely food
insecure became food secure, after controlling for covariates. Conclusion:
Household food insecurity has a pervasive graded negative effect on a variety of
mental health outcomes, in which significantly higher levels of food insecurity
are associated with a higher risk of adverse mental health outcomes. Reduction of
food insecurity, particularly at the severe level, is a public health concern and
a modifiable structural determinant of health worthy of macro-level policy
intervention.
PMID- 29349240
TI - Explaining racial/ethnic differences in all-cause mortality in the Multi-Ethnic
Study of Atherosclerosis (MESA): Substantive complexity and hazardous working
conditions as mediating factors.
AB - Research on racial/ethnic health disparities and socioeconomic position has not
fully considered occupation. However, because occupations are racially patterned,
certain occupational characteristics may explain racial/ethnic difference in
health. This study examines the role of occupational characteristics in
racial/ethnic disparities in all-cause mortality. Data are from a U.S. community
based cohort study (n=6342, median follow-up: 12.2 years), in which 893 deaths
(14.1%) occurred. We estimated mortality hazard ratios (HRs) for African
Americans, Hispanics, and Chinese Americans compared with whites. We also
estimated the proportion of the HR mediated by each of two occupational
characteristics, substantive complexity of work (e.g., problem solving,
inductive/deductive reasoning on the job) and hazardous conditions (e.g., noise,
extreme temperature, chemicals), derived from the Occupational Information
Network database (O*NET). Analyses were adjusted for age, sex, nativity, working
status at baseline, and study sites. African Americans had a higher rate of all
cause death (HR 1.41; 95% confidence interval [CI]: 1.19-1.66) than whites.
Chinese-American ethnicity was protective (HR 0.59, CI: 0.40-0.85); Hispanic
ethnicity was not significantly different from whites (HR 0.88; CI: 0.67-1.17).
Substantive complexity of work mediated 30% of the higher rate of death for
African Americans compared with whites. For other groups, mediation was not
significant. Hazardous conditions did not significantly mediate mortality in any
racial/ethnic group. Lower levels of substantive complexity of work mediate a
substantial part of the health disadvantage in African Americans. This job
characteristic may be an important factor in explaining racial health
disparities.
PMID- 29349241
TI - Simultaneous evaluation of physical and social environmental correlates of
physical activity in adults: A systematic review.
AB - Background: Ecological models of physical activity posit that social and physical
environmental features exert independent and interactive influences on physical
activity, but previous research has focussed on independent influences. This
systematic review aimed to synthesise the literature investigating how features
of neighbourhood physical and social environments are associated with physical
activity when both levels of influence are simultaneously considered, and to
assess progress in the exploration of interactive effects of social and physical
environmental correlates on physical activity. Methods: A systematic literature
search was conducted in February 2016. Articles were included if they used an
adult (>=15 years) sample, simultaneously considered at least one physical and
one social environmental characteristic in a single statistical model, used self
reported or objectively-measured physical activity as a primary outcome, reported
findings from quantitative, observational analyses and were published in a peer
reviewed journal. Combined measures including social and physical environment
items were excluded as they didn't permit investigation of independent and
interactive social and physical effects. Forty-six studies were identified.
Results: An inconsistent evidence base for independent environmental correlates
of physical activity was revealed, with some support for specific physical and
social environment correlates. Most studies found significant associations
between physical activity and both physical and social environmental variables.
There was preliminary evidence that physical and social environmental variables
had interactive effects on activity, although only 4 studies examined interactive
effects. Conclusions: Inconsistent evidence of independent associations between
environmental variables and physical activity could be partly due to unmeasured
effect modification (e.g. interactive effects) creating unaccounted variance in
relationships between the environment and activity. Results supported multiple
levels of environmental influence on physical activity. It is recommended that
further research uses simultaneous or interaction analyses to gain insight into
complex relationships between neighbourhood social and physical environments and
physical activity, as there is currently limited research in this area.
PMID- 29349242
TI - The negative effects on mental health of being in a non-desired occupation in an
increasingly precarious labour market.
AB - Precarious employment has been associated with poor mental health. Moreover,
increasing labour market precariousness may cause individuals to feel 'locked
in', in non-desired workplaces or occupations, out of fear of not finding a new
employment. This could be experienced as a 'loss of control', with similar
negative health consequences. It is plausible that the extent to which being in a
non-desired occupation (NDO) or being in precarious employment (PE) has a
negative impact on mental health differs according to age group. We tested this
hypothesis using data from 2331 persons, 18-34, 35-44, and 45-54 years old, who
answered questionnaires in 1999/2000, 2005, and 2010. Incidence rate ratios (IRR)
were calculated for poor mental health (GHQ-12) in 2010, after exposure to NDO
and PE in 1999/2000 or 2005. NDO and PE were more common in the youngest age
group, and they were both associated with poor mental health. In the middle age
group the impact of NDO was null, while in contrast the IRR for PE was 1.7 (95%
CI: 1.3-2.3) after full adjustment. The pattern was completely the opposite in
the oldest age group (adjusted IRR for NDO 1.6 (1.1-2.4) and for PE 0.9 (0.6
1.4)). The population attributable fraction of poor mental health was 14.2% and
11.6%, respectively, for NDO in the youngest and oldest age group, and 17.2% for
PE in the middle age group. While the consequences of PE have been widely
discussed, those of NDO have not received attention. Interventions aimed at
adapting work situations for older individuals and facilitating conditions of job
change in such a way as to avoid risking unemployment or precarious employment
situations may lead to improved mental health in this age group.
PMID- 29349243
TI - Women's television watching and reproductive health behavior in Bangladesh.
AB - Bangladesh has made significant social, economic, and health progress in recent
decades, yet many reproductive health indicators remain weak. Access to
television (TV) is increasing rapidly and provides a potential mechanism for
influencing health behavior. We present a conceptual framework for the influence
of different types of TV exposure on individual's aspirations and health behavior
through the mechanisms of observational learning and ideational change. We
analyze data from two large national surveys conducted in 2010 and 2011 to
examine the association between women's TV watching and five reproductive health
behaviors controlling for the effects of observed confounders. We find that TV
watchers are significantly more likely to desire fewer children, are more likely
to use contraceptives, and are less likely to have a birth in the two years
before the survey. They are more likely to seek at least four antenatal care
visits and to utilize a skilled birth attendant. Consequently, continued increase
in the reach of TV and associated growth in TV viewing is potentially an
important driver of health behaviors in the country.
PMID- 29349244
TI - Trends in social inequality in physical inactivity among Danish adolescents 1991
2014.
AB - The aim of this study was to investigate social inequality in physical inactivity
among adolescents from 1991 to 2014 and to describe any changes in inequality
during this period. The analyses were based on data from the Danish part of the
HBSC study, which consists of seven comparable cross-sectional studies of
nationally representative samples of 11-15-year old adolescents. The available
data consisted of weekly time (hours) spent on vigorous physical activity and
parental occupation from 30,974 participants. In summary, 8.0% of the adolescents
reported to be physically inactive, i.e. spend zero hours of vigorous leisure
time physical activity per week. The proportion of physically inactive
adolescents was 5.4% in high social class and 7.8% and 10.8%, respectively, in
middle and low social class. The absolute social inequality measured as
prevalence difference between low and high social class did not change
systematically across the observation period from 1991 to 2014. Compared to high
social class, OR (95% CI) for physical inactivity was 1.48 (1.32-1.65) in middle
social class and 2.18 (1.92-2.47) in lower social class. This relative social
inequality was similar in the seven data collection waves (p=0.971). Although the
gap in physical inactivity between social classes does not seem to be widening in
Danish adolescents, there are still considerable differences in the activity
levels between high, middle and low social class adolescents. Consequently, there
is a need for a targeted physical activity intervention among adolescents from
low (and middle) social class.
PMID- 29349245
TI - Mental health of sub-saharan african migrants: The gendered role of migration
paths and transnational ties.
AB - In Europe, migrants are at higher risk of common mental disorders or
psychological distress than are natives. Little is known regarding the social
determinants of migrant mental health, particularly the roles played by migration
conditions and transnational practices, which may manifest themselves in
different ways for men and for women. The goal of this paper was to understand
the gendered roles of migration paths and transnational ties in mental health
among sub-Saharan African migrants residing in the Paris, France, metropolitan
area. This study used data from the Parcours study conducted in 2012-2013, which
employed a life-event approach to collect data from a representative sample of
migrants who visited healthcare facilities (n = 2468). We measured anxiety and
depressive symptoms at the time of data collection with the Patient Health
Questionnaire-4 (PHQ-4). Reasons for migration, the living conditions in the host
country and transnational ties after migration were taken into account by sex and
after adjustment. Our study demonstrates that among sub-Saharan African migrants,
mental health is related to the migratory path and the migrant's situation in the
host country but differently for women and men. Among women, anxiety and
depressive symptoms were strongly related to having left one's home country
because of threats to one's life. Among men, residing illegally in the host
country was related to impaired mental health. For both women and men, cross
border separation from a child less than 18 years old was not independently
associated with anxiety and depressive symptoms. In addition, social and
emotional support from relatives and friends-both from the society of origin and
of destination-were associated with lower anxiety and depressive symptoms.
Migrant mental health may be impaired in the current context of anti-migrant
policies and an anti-immigrant social environment in Europe.
PMID- 29349246
TI - Feasibility of a novel participatory multi-sector continuous improvement approach
to enhance food security in remote Indigenous Australian communities.
AB - Background: Food insecurity underlies and compounds many of the development
issues faced by remote Indigenous communities in Australia. Multi-sector
approaches offer promise to improve food security. We assessed the feasibility of
a novel multi-sector approach to enhance community food security in remote
Indigenous Australia. Method: A longitudinal comparative multi-site case study,
the Good Food Systems Good Food for All Project, was conducted (2009-2013) with
four Aboriginal communities. Continuous improvement meetings were held in each
community. Data from project documents and store sales were used to assess
feasibility according to engagement, uptake and sustainability of action, and
impact on community diet, as well as identifying conditions facilitating or
hindering these. Results: Engagement was established where: the community
perceived a need for the approach; where trust was developed between the
community and facilitators; where there was community stability; and where
flexibility was applied in the timing of meetings. The approach enabled
stakeholders in each community to collectively appraise the community food system
and plan action. Actions that could be directly implemented within available
resources resulted from developing collaborative capacity. Actions requiring
advocacy, multi-sectoral involvement, commitment or further resources were less
frequently used. Positive shifts in community diet were associated with key areas
where actions were implemented. Conclusion: A multi-sector participatory approach
seeking continuous improvement engaged committed Aboriginal and non-Aboriginal
stakeholders and was shown to have potential to shift community diet. Provision
of clear mechanisms to link this approach with higher level policy and decision
making structures, clarity of roles and responsibilities, and processes to
prioritise and communicate actions across sectors should further strengthen
capacity for food security improvement. Integrating this approach enabling local
decision-making into community governance structures with adequate resourcing is
an imperative.
PMID- 29349247
TI - Incorporating biomarkers into the study of socio-economic status and health among
older adults in China.
AB - The social gradient in health - that individuals with lower SES have worse health
than those with higher SES- is welldocumented using self-reports of health in
more developed countries. Less is known about the relationship between SES and
health biomarkers among older adults residing in less developed countries. We use
data from the ChineseLongitudinal Healthy Longevity Survey (CLHLS) longevity
areas sub-sample to examine the social gradient in healthamong rural young-old
and oldest-old adults (N=2,121). Our health indicators include individual
biomarkers, metabolic syndrome, and self-reports of health. We found a largely
positive relationship between SES and health. SES was more consistently
associated with individual biomarkers among the oldest-old than the young-old,
providing evidence for cumulative disadvantage. We discuss the implications of
our findings for older adults who have lived through different social, economic,
and health regimes.
PMID- 29349248
TI - Association of financial hardship with poor sleep health outcomes among men who
have sex with men.
AB - Previous studies have identified an association between socioeconomic status and
sleep health. While some research has studied this association among sexual
minority groups, including men who have sex with men (MSM), they exclusively
focused on US-based populations. The interplay between the two in shaping sleep
health has not been previously examined on populations residing outside the US.
This study considers both determinants, by investigating whether financial
hardship is associated with sleep health among a sample of MSM in Paris, France.
Broadcast advertisements were placed on a popular geosocial-networking smartphone
application for MSM to direct users in Paris to a web-based survey measuring
financial hardship and five dimensions of sleep health as well as socio
demographic characteristics. Modified Poisson models with robust error variance
were computed to estimate risk ratios (RRs) and 95% confidence intervals (CI) for
the associations between financial hardship and the following self-reported
outcomes: 1) poor sleep quality, 2) short sleep duration; and 3) sleep problems.
In total, 580 respondents completed the survey. In this sample, both financial
hardship and poor sleep health were common - 45.5% reported that it was
extremely, very, or somewhat difficult for them to meet their monthly payments on
bills (referred to as "high financial hardship") and 30.1% rated their sleep as
fairly bad or very bad (referred to as "poor sleep quality"). Multivariate models
revealed that, compared to participants who reported low financial hardship,
those who reported high financial hardship were more likely to report poor sleep
quality (aRR: 1.35, 95% CI: 1.04, 1.77), to report problems falling asleep (aRR:
1.23, 95% CI: 1.02, 1.49), and to report problems staying awake in the daytime
(aRR: 3.12, 95% CI: 1.83, 5.31). Future research should investigate whether this
relationship is causal and determine whether interventions to reduce financial
hardships could promote sleep health among MSM.
PMID- 29349249
TI - The differential effects of rural health care access on race-specific mortality.
AB - We examined the relationship between race-specific rural mortality and the health
infrastructure of rural counties in light of America's recent emergence of a
rural mortality penalty. Using the Compressed Mortality File from National Center
for Health Statistics (2008-2012) and county-level demographic, socioeconomic,
and health care indicators from the Area Health Resource File and the US Census,
we created a rural public health infrastructure index which encompasses four
types of health care access (public health employees, critical access
hospital/rural referral centers, rural health clinics, and emergency departments)
within counties. We found that each unit increase in the index is associated with
a decline in rural Black mortality, but is associated with an increase in rural
White mortality. Policymakers could benefit from focusing on the declining rate
of mortality improvement in many rural regions, specifically by trying to better
understand how decisions concerning public health spending may influence
mortality differently for Black and White residents.
PMID- 29349250
TI - Best-worst scaling survey of preferences regarding the adverse effects of tobacco
use in China.
AB - We use best-worst scaling to assess two types of concern levels of the adverse
consequences of smoking in China. While the smoking cessation policy has worked
well in Taiwan, more than 1 million people in mainland China are estimated to die
every year from tobacco use. This study compares the preferences of Chinese
individuals in the two jurisdictions (mainland versus Taiwan) and explores the
possibility of information-based interventions. The relative importance of 13
adverse effects was assessed by conducting a web-based survey on a sample of 480
Chinese participants. The 13 items consist of various adverse effects of tobacco
use: from long-term health risk, such as lung cancer and cardiovascular diseases,
to reduction of physical capacity and sexual dysfunction, and disturbance to non
smokers. The resulting data suggest possible strategies to curb smoking. Subgroup
analysis, focusing on gender, smoking status, and nicotine dependence, was also
conducted. Lung cancer, cardiovascular diseases, and chronic obstructive
pulmonary disease, in this order, rank highest for both types of respondents. On
the other hand, high expenditures (13th) and weight gain after cessation (12th)
are the lowest ranked for both. Measuring individual best-worst scores reveals
substantial heterogeneity among respondents and that information-based
intervention can help curb smoking.
PMID- 29349251
TI - Undiagnosed depression: A community diagnosis.
AB - Many large provider networks are investing heavily in preventing disease within
the communities that they serve. We explore the potential benefits and challenges
associated with tackling depression at the community level using a unique dataset
designed for one such provider network. The economic costs of having depression
(increased medical care use, lower quality of life, and decreased workplace
productivity) are among the highest of any disease. Depression often goes
undiagnosed, yet many believe that depression can be treated or prevented
altogether. We explore the prevalence, distribution, economic burden, and the
psychosocial and economic factors associated with undiagnosed depression in a
lower-income neighborhood in northern Manhattan. Even using state-of-the art data
to "diagnose" the risk factors within a community, it can be challenging for
provider networks to act against such risk factors.
PMID- 29349252
TI - Wealth, justice and freedom: Objective and subjective measures predicting poor
mental health in a study across eight countries.
AB - Background: Macro-level factors (MF) such as wealth, justice and freedom measured
with objective country-level indicators (objective MF), for instance the Gross
Domestic Product (GDP), have been investigated in relation to health and well
being, but rarely in connection with depression, anxiety and stress subsumed as
poor mental health. Also, a combination of different objective MF and of how
individuals perceive those MF (subjective MF) has not been taken into
consideration. In the present study, we combined subjective and objective
measures of wealth, justice and freedom and examined their relationship with poor
mental health. Method: Population-based interviews were conducted in France,
Germany, Poland, Russia, Spain, Sweden, U.K. and U.S.A. (n ~ 1000 per country).
GDP, GINI coefficient, Justice Index and Freedom Index were used as objective MF,
whereas subjective MF were perceived wealth, justice and freedom measured at the
individual level. Poor mental health was assessed as a combination of symptoms of
depression, anxiety and stress. Results: In a random-intercept-model, GINI
coefficient and Freedom Index were significant positive country-level, and
perceived wealth, justice, and freedom significant negative individual-level
predictors of symptoms of poor mental health. Conclusion: Multiple subjective and
objective MF should be combined to assess the macrosystem's relationship with
poor mental health more precisely. The relationship between MF and poor mental
health indicates that the macrosystem should be taken into account as relevant
context for mental health problems, too.
PMID- 29349253
TI - Recreational marijuana legalization and college student use: Early evidence.
AB - We analyze marijuana use by college undergraduates before and after legalization
of recreational marijuana. Using survey data from the National College Health
Assessment, we show that students at Washington State University experienced a
significant increase in marijuana use after legalization. This increase is larger
than would be predicted by national trends. The change is strongest among
females, Black students, and Hispanic students. The increase for underage
students is as much as for legal-age students. We find no corresponding changes
in the consumption of tobacco, alcohol, or other drugs.
PMID- 29349254
TI - Prevalence of psychological distress and its association with socio-demographic
and HIV-risk factors in South Africa: Findings of the 2012 HIV prevalence,
incidence and behaviour survey.
AB - Background: In South Africa, there are limited nationally representative data on
the prevalence and factors associated with psychological distress. This study
used a 2012 nationally representative population-based household survey to
investigate factors associated with psychological distress in South Africa.
Methods: The survey is based on a multistage stratified cross-sectional design.
Univariate and multivariate logistic regression models were fitted to identify
factors associated with psychological distress. Results: Out of a total 25860
participants, 23.9% reported psychological distress. Higher likelihood of
reporting psychological distress was significantly associated with being female
[OR = 1.68 (95% CI: 1.34-2.10), p < 0.001], aged 25 to 49 years [OR = 1.35 (95%
CI: 1.08-1.70), p = 0.010] and 50 years and older [OR = 1.44 (95% CI: 1.06-1.97),
p = 0.023)], Black Africans [OR = 1.61 (95% CI: 1.24-2.10), p < 0.001)], a high
risk drinker [OR = 1.37 (95% CI: 1.02-1.83), p = 0.037], a hazardous drinker [OR
= 4.76 (95% CI: 2.69-8.42), p < 0.001] and HIV positive, [OR = 1.79 (95% CI:1.55
2.08) p < 0.001], while lower likelihood of reporting psychological distress was
significantly associated with being married [OR = 0.78 (95% CI: 0.62-0.98), p =
0.031), employed [OR = 0.71 (95% CI: 0.57-0.88), p = 0.002], and living in a
rural formal area [OR = 0.73 (95% CI: 0.55-0.97), p = 0.033]. Conclusion: There
is a need to develop strategies to alleviate psychological distress in the
general population, with a particular focus on those who may be more vulnerable
to distress such as females, the aged, excessive alcohol users, the unemployed,
people living with HIV and those residing in urban areas as identified in the
current findings.
PMID- 29349255
TI - Gender-specific associations between involvement in team sport culture and
canadian adolescents' substance-use behavior.
AB - Canadian adolescents have some of the highest rates of substance use in the
world. The etiology of this phenomenon has not been fully explored, and one
possible contextual determinant is involvement in sport activities that foster
risk-taking behaviors through physical and social mechanisms. Using the 2013-14
Health Behaviour in School Aged Children (HBSC) study we therefore examined this
hypothesis in a contemporary national sample of Canadian adolescents. The
strength and direction of the relationship between sport and substance use varied
by gender and substance, with team sport participation associated with increased
binge drinking (RR 1.33 [95% CI 1.13-1.56] for boys, RR 1.21 [1.06-1.38] for
girls) and use of smokeless tobacco (RR 1.68 [1.34-2.10] for boys, RR 1.32 [1.01
1.72] for girls), but with lower prevalence levels of cannabis use (RR 0.73 [95%
CI 0.61-0.88]) and cigarette smoking (RR 0.79 [95% CI 0.70-0.89]) in girls alone.
We also compared team sport athletes with high social involvement (sports team as
primary peer group) and physical involvement (higher number of days/week
physically active) to those with low involvement. For boys, the combination of
high physical and high social involvement was associated with the highest risk,
while high social involvement alone was associated with the greatest risk for
girls. While team sport participation confers only a small increased risk for
substance use, the prevalence of sport participation results in a large
population impact. Given this fact, interventions such as education for parents
and coaches and policies encouraging engagement in a variety of extracurricular
activities should be explored.
PMID- 29349256
TI - Income and the mental health of Canadian mothers: Evidence from the Universal
Child Care Benefit.
AB - The Universal Child Care Benefit, introduced in 2006, was an income transfer for
Canadian families with young children. I exploit this exogenous increase in
income to answer the following questions: (1) Is there a relationship between
income and mental health among Canadian mothers? (2) Is it corroborated by other
measures of well-being (i.e. stress, life satisfaction)? (3) Is the effect
different for lone mothers compared to those in two-parent families? I answer
these questions using a difference-in-differences model and microdata from the
Canadian Community Health Survey, 2003 to 2008. The estimating sample includes
26,886 mothers, 6273 of whom are lone parents. I find the income transfer
improved mental health and life satisfaction regardless of family structure,
albeit not necessarily for a given individual. Rather, average scores were higher
for mothers with young children after implementation of the Universal Child Care
Benefit. For example, they were more likely to report 'excellent' mental health
and less likely to be in each of the other categories. The transfer also reduced
stress among lone mothers with young children. Specifically, they were less
likely to be 'quite a bit' or 'extremely' stressed on a daily basis, and more
likely to be 'not at all' or 'not very' stressed. I argue that assumptions of the
model are plausible and show that results are consistent across several
robustness checks.
PMID- 29349257
TI - The tyranny of the averages and the indiscriminate use of risk factors in public
health: The case of coronary heart disease.
AB - Modern medicine is overwhelmed by a plethora of both established risk factors and
novel biomarkers for diseases. The majority of this information is expressed by
probabilistic measures of association such as the odds ratio (OR) obtained by
calculating differences in average "risk" between exposed and unexposed groups.
However, recent research demonstrates that even ORs of considerable magnitude are
insufficient for assessing the ability of risk factors or biomarkers to
distinguish the individuals who will develop the disease from those who will not.
In regards to coronary heart disease (CHD), we already know that novel biomarkers
add very little to the discriminatory accuracy (DA) of traditional risk factors.
However, the value added by traditional risk factors alongside simple demographic
variables such as age and sex has been the subject of less discussion. Moreover,
in public health, we use the OR to calculate the population attributable fraction
(PAF), although this measure fails to consider the DA of the risk factor it
represents. Therefore, focusing on CHD and applying measures of DA, we re-examine
the role of individual demographic characteristics, risk factors, novel
biomarkers and PAFs in public health and epidemiology. In so doing, we also raise
a more general criticism of the traditional risk factors' epidemiology. We
investigated a cohort of 6103 men and women who participated in the baseline
(1991-1996) of the Malmo Diet and Cancer study and were followed for 18 years. We
found that neither traditional risk factors nor biomarkers substantially improved
the DA obtained by models considering only age and sex. We concluded that the PAF
measure provided insufficient information for the planning of preventive
strategies in the population. We need a better understanding of the individual
heterogeneity around the averages and, thereby, a fundamental change in the way
we interpret risk factors in public health and epidemiology.
PMID- 29349258
TI - Neighborhood context and birth outcomes: Going beyond neighborhood disadvantage,
incorporating affluence.
AB - *Neighborhood affluence protects against the risk of poor birth outcome. *The
protective effect of affluence holds for Whites, Blacks, Hispanics and Asians.
*Mediation of these pathways by prenatal smoking varies by racial group. *The
discourse on neighborhoods and birth outcomes should include affluence.
PMID- 29349259
TI - Access and quality of parks and associations with obesity: A cross-sectional
study.
AB - Public health is increasingly engaging with multi-faceted obesity prevention
efforts. Although parks represent key community assets for broader public health,
they may not be distributed equitably and associations with obesity are
equivocal. We investigated park access and quality relative to deprivation and
obesity with individual-level data from the Yorkshire Health Study. Compared to
the least deprived areas, the moderately and most deprived areas had a greater
park access and park quality in terms of features and amenities. However, parks
in the moderately and most deprived areas also had the most safety concerns and
incivilities. Although deprivation was associated with obesity, contrary to
current policy guidance, both park access and quality appear less important for
understanding variations in obesity within this study. Although sub-group
analyses by deprivation tertile revealed that low quality park amenities in
highly and moderately deprived areas may be important for understanding obesity
prevalence, all other associations were non-significant.
PMID- 29349260
TI - Environmental radiation level, radiation anxiety, and psychological distress of
non-evacuee residents in Fukushima five years after the Great East Japan
Earthquake: Multilevel analyses.
AB - The present study aimed to clarify the associations among radiation exposure or
psychological exposure to the Fukushima nuclear power plant accident (i.e.,
fear/anxiety immediately after the accident), current radiation anxiety, and
psychological distress among non-evacuee community residents in Fukushima five
years after the Great East Japan Earthquake, which occurred in March 2011. A
questionnaire survey was administered to a random sample of non-evacuee community
residents from 49 municipalities of Fukushima prefecture from February to April
2016, and data from 1684 respondents (34.4%) were analyzed. Environmental
radiation levels at the time of the accident were ascertained from survey meter
data, while environmental radiation levels at the time of the survey were
ascertained from monitoring post data. In the questionnaire, immediate
fear/anxiety after the accident, current radiation anxiety, and psychological
distress were measured using a single-item question, a 7-item scale, and K6,
respectively. Multilevel linear or logistic regression models were applied to
analyze the determinants of radiation anxiety and psychological distress. The
findings showed that environmental radiation levels at the time of the survey
were more strongly associated with radiation anxiety than radiation levels
immediately after the accident. Disaster-related experiences, such as direct
damage, disaster-related family stress, and fear/anxiety after the accident, and
demographic characteristics (e.g., younger age, being married, low socioeconomic
status) were significantly associated with radiation anxiety. Environmental
radiation levels at the time of the accident or survey were not significantly
associated with psychological distress. Radiation anxiety largely mediated the
association between fear/anxiety after the accident and psychological distress.
In addition to environmental radiation levels, respondents' radiation anxiety was
affected by multiple factors, such as disaster-related experiences and
demographic characteristics. Radiation levels were not associated with
psychological distress in non-evacuee community residents. Rather, fear/anxiety
after the nuclear power plant accident may be a determinant of psychological
distress, mediated by radiation anxiety.
PMID- 29349261
TI - The impact of the UK National Minimum Wage on mental health.
AB - Despite an emerging literature, there is still sparse and mixed evidence on the
wider societal benefits of Minimum Wage policies, including their effects on
mental health. Furthermore, causal evidence on the relationship between earnings
and mental health is limited. We focus on low-wage earners, who are at higher
risk of psychological distress, and exploit the quasi-experiment provided by the
introduction of the UK National Minimum Wage (NMW) to identify the causal impact
of wage increases on mental health. We employ difference-in-differences models
and find that the introduction of the UK NMW had no effect on mental health. Our
estimates do not appear to support earlier findings which indicate that minimum
wages affect mental health of low-wage earners. A series of robustness checks
accounting for measurement error, as well as treatment and control group
composition, confirm our main results. Overall, our findings suggest that
policies aimed at improving the mental health of low-wage earners should either
consider the non-wage characteristics of employment or potentially larger wage
increases.
PMID- 29349262
TI - Mothers' labor market choices and child development outcomes in Chile.
AB - This paper examines associations between labor market participation of Chilean
mothers and the cognitive, language, and socio-economic development of their
children. Using a nationally-representative sample of 3-year-old children, we
test if mothers' work intensity in the two previous years is associated with
child development outcomes; data were collected in 2010 when children were one
year old, and again in 2012, when they were three years old. We find that
children who were three years old with mothers who worked for higher fractions of
their children's lives in the previous two years perform significantly better on
all tests (cognitive, language, socio-emotional) than children whose mothers had
worked less, while controlling for baseline test performance. These main effects
did not remain significant with the inclusion of a wide range of socio-economic,
demographic control variables, however. Our results were similarly null when
using an IV analysis or a propensity score matching approach. We provide
descriptive information on theoretical pathways by which maternal work may
influence child development. Though several of these pathways (e.g. preschool,
toys, maternal stress) seem to be associated with both maternal work and child
development outcomes, the pathways are not sufficiently strong to generate an
association between maternal work and child development. We conclude that Chilean
mothers' employment in early childhood generally does not have an effect on child
development.
PMID- 29349263
TI - Worldviews and trust of sources for health information on electronic nicotine
delivery systems: Effects on risk perceptions and use.
AB - Public health agencies, the news media, and the tobacco/vapor industry have
issued contradictory statements about the health effects of electronic nicotine
delivery systems (ENDS). We investigated the levels of trust that consumers place
in different information sources and how trust is associated with cultural
worldviews, risk perceptions, ENDS use, and sociodemographic characteristics
using a nationally representative sample of 6051 U.S. adults in 2015. Seventeen
percent of adults were uncertain about their trust for one or more potential
sources. Among the rest, the Centers for Disease Control and Prevention (CDC),
health experts, and the Food & Drug Administration (FDA) elicited the highest
levels of trust. In contrast, tobacco and vapor manufacturers, vape shop
employees, and, to a lesser extent, the news media were distrusted. Adults who
had higher incomes and more education or espoused egalitarian and communitarian
worldviews expressed more trust in health sources and the FDA, whereas those
identifying as non-Hispanic Black or multiracial reported less trust. Current
smokers, those who identified as non-Hispanic Black or other race, had lower
incomes, and espoused hierarchy and individualism worldviews expressed less
distrust toward the tobacco and vapor industry. Greater trust (or less distrust)
toward the tobacco and vapor industry and an individualism worldview were
associated with perceptions of lower risk of premature death from daily ENDS use,
greater uncertainty about those risks, and greater odds of using ENDS. Public
health and the FDA should consider consumer trust and worldviews in the design
and regulation of public education campaigns regarding the potential health risks
and benefits of ENDS.
PMID- 29349264
TI - Life course influences on later life health in China: Childhood health exposure
and socioeconomic mediators during adulthood.
AB - China's unprecedented population aging and social and economic change raise
important issues concerning life course determinants of advantage or disadvantage
into later life. Data from the China Health and Retirement Longitudinal Study
(CHARLS) 2013 were analysed to identify the influence of childhood health on
later life health as indicated by self-rated health and how this influence could
be mediated by social and economic positions (SEP) and resources later in the
life span. CHARLS provides nationally representative data on 18, 000 individuals
aged 45 years and above in approximately 150 districts and 450 villages. Both
multivariate logit regression model and KHB method (Karlson/Holm/Breen method)
were applied to examine and decompose the life span influences on later life
health. The results show that the childhood health, accounts for approximately
half of the effect directly and another half of the effect indirectly through
social and economic variations during adulthood. Relative living standard,
marital status and urban residence are the most significant and important social
and economic mediators for men; For women, living standard and secondary
schooling are most influential while marital status is not significant.
Implications for social and economic policies to improve later life health are
discussed.
PMID- 29349265
TI - Children's migration and chronic illness among older parents 'left behind' in
China.
AB - The relationship between adult children's migration and the health of their older
parents 'left behind' is an emerging research area and existing studies reflect
mixed findings. This study aims to investigate the association between having
migrant (adult) children and older parents' chronic illness in China, using
chronic stomach or other digestive diseases as a proxy. Secondary analysis of the
national baseline survey of the 2011 China Health and Retirement Longitudinal
Study (CHARLS) was conducted. Analyses were conducted in a total of sample of
6495 individuals aged 60 years and above from 28 out of 31 provinces in China,
who had at least one child at the baseline survey. Binary logistic regression was
used. The prevalence of any of the diagnosed conditions of chronic stomach or
other digestive diseases was higher among older people with a migrant son than
among those without (27 percent vs 21 percent, p < 0.001). More specifically, the
odds ratio of reporting a disease was higher among older adults with at least one
adult son living in another county or province than among those with all their
sons living closer (OR = 1.29, 95% CI = 1.10-1.51). The results from this large
sample of older adults support the hypothesis that migration of sons
significantly increases the risk of chronic stomach and other digestive diseases
among 'left behind' elderly parents in contemporary China.
PMID- 29349266
TI - Can we determine whether physical limitations are more prevalent in the US than
in countries with comparable life expectancy?
AB - We evaluate the variability in estimates of self-reported physical limitations by
age across four nationally representative surveys in the US. We consider its
implications for determining whether, as previous literature suggests, the US
estimates reveal limitations at an earlier age than in three countries with
similar life expectancy: England, Taiwan, and Costa Rica. Based on cross
sectional data from seven population-based surveys, we use local mean smoothing
to plot self-reported limitations by age for each of four physical tasks for each
survey, stratified by sex. We find substantial variation in the estimates in the
US across four nationally-representative surveys. For example, one US survey
suggests that American women experience a walking limitation 15 years earlier
than their Costa Rican counterparts, while another US survey implies that
Americans have a 4-year advantage. Differences in mode of survey may account for
higher prevalence of limitations in the one survey that used a self-administered
mail-in questionnaire than in the other surveys that used in-person or telephone
interviews. Yet, even among US surveys that used the same mode, there is still so
much variability in estimates that we cannot conclude whether Americans have
better or worse function than their counterparts in the other countries.
Seemingly minor differences in question wording and response categories may
account for the remaining inconsistency. If minor differences in question wording
can result in such extensive variation in the estimates within a given
population, then lack of comparability is likely to be an even greater problem
when examining results across countries that do not share the same language or
culture. Despite the potential utility of self-reported physical function within
a survey sample, our findings imply that absolute estimates of population-level
prevalence of self-reported physical limitations are unlikely to be strictly
comparable across countries-or even across surveys within the same population.
PMID- 29349267
TI - Subjective health and well-being: Toward robust cross-cultural comparisons.
PMID- 29349269
TI - Fertility behaviors in South Korea and their association with ultrasound prenatal
sex screening.
AB - Imbalances in the sex ratio at birth in Southeast and East Asia increased
especially after the mid-1980s. We study how ultrasonic technology affected sex
ratios at birth in South Korea, a country with a strong son preference. Between
1985 and 1995 fetal screenings and abortion services were widely available,
though not available in the years before, and prohibited in the years after.
Using the 1985, 1995, and 2005 Census microdata, we examine changes in sex ratios
of newborns by birth year. We then study periodic effects on the fertility
stopping rule, using the 2006 Korean Longitudinal Study of Aging, which provides
birth years for all children. Between 1985 and 1995 there was a large increase in
the fraction of boy babies at birth orders of three or more. Despite these
fractions falling in the subsequent time period when fetal screening became
illegal, they remained above plausible biological levels. Supporting earlier
findings in the literature, the increase in sex ratios was especially large when
prior sibling composition was entirely female. We also find that having only
daughters significantly increases the probability of parents having another
child, and this effect is greater for parents with any child born after 1985 than
the parents with all children born before 1985. There exist significant period
effects, suggesting that sex ratios at birth became imbalanced when ultrasound
technology became available. The availability of ultrasound technology also
influenced parents' fertility decisions, seen especially in parents with only
daughters deciding to have another child. Our study provides new evidence for how
the availability of ultrasound technology influenced sex ratios at birth and
influenced fertility behaviors in Korea.
PMID- 29349268
TI - Socioeconomic status indicators and common mental disorders: Evidence from a
study of prenatal depression in Pakistan.
AB - There is growing interest in the relationship between socioeconomic status (SES),
poverty, and mental health in low and middle-income countries (LMIC). However, it
is not clear whether a gradient approach focused on a wider SES distribution or a
binary poverty approach is more salient for mental health in LMIC. Yet this
distinction has implications for interventions aimed at improving population
health. We contribute to the literature by examining how multiple indicators of
socioeconomic status, including gradient SES and binary poverty indicators,
contribute to prenatal depression symptoms in a LMIC context. Prenatal depression
is an important public health concern with negative sequela for the mother and
her children. We use data on assets, education, food insecurity, debt, and
depression symptoms from a sample of 1154 pregnant women residing in rural
Pakistan. Women who screened positive for depression participated in a cluster
randomized controlled trial of a perinatal depression intervention; all women
were interviewed October 2015-February 2016, prior to the start of the
intervention. Cluster-specific sampling weights were used to approximate a random
sample of pregnant women in the area. Findings indicate that fewer assets,
experiencing food insecurity, and having household debt are independently
associated with worse depression symptoms. The association with assets is linear
with no evidence of a threshold effect, supporting the idea of a gradient in the
association between levels of SES and depression symptoms. A gradient was also
initially observed with woman's educational attainment, but this association was
attenuated once other SES variables were included in the model. Together, the
asset, food insecurity, and debt indicators explain 14% of the variance in
depression symptoms, more than has been reported in high income country studies.
These findings support the use of multiple SES indicators to better elucidate the
complex relationship between socioeconomic status and mental health in LMIC.
PMID- 29349270
TI - Breaking down the monolith: Understanding flu vaccine uptake among African
Americans.
AB - Black adults are significantly less likely to be immunized for seasonal influenza
when compared to Whites. This persistent disparity contributes to increased
influenza-related morbidity and mortality in the African American population.
Most scholarship on vaccine disparities has compared Whites and Blacks. Employing
Public Health Critical Race Praxis, this study seeks to shift the focus to
explore differences within the Black population. Utilizing a nationally
representative 2015 survey of US Black adults (n = 806), we explore differences
by gender, age, income, and education across vaccine-related measures (e.g.,
perceived risk, knowledge, attitudes) and racial factors (e.g. racial salience,
racial fairness, perceived discrimination). We also explore differences by
vaccine behavior in the past five years among those who vaccinate every year,
most years but not all, once or twice, and never. Greater frequency of flu
vaccine uptake was associated with better self-reported vaccine knowledge, more
positive vaccine attitudes, more trust in the flu vaccine and the vaccine
process, higher perceived disease risk, lower perceived risk of vaccine side
effects, stronger subjective and moral norms, lower general vaccine hesitancy,
higher confidence in the flu vaccine, and lower perceived barriers. Logistic
regression results highlighted other significant differences among the groups,
emphasizing areas to target for improved vaccination rates. We find great
diversity within the Black community related to influenza immunization decisions,
highlighting the need to "break down the monolith" in future research.
PMID- 29349271
TI - Becoming a 'pharmaceutical person': Medication use trajectories from age 26 to 38
in a representative birth cohort from Dunedin, New Zealand.
AB - Despite the abundance of medications available for human consumption, and
frequent concerns about increasing medicalization or pharmaceuticalization of
everyday life, there is little research investigating medicines-use in young and
middle-aged populations and discussing the implications of young people using
increasing numbers of medicines and becoming pharmaceutical users over time. We
use data from a New Zealand longitudinal study to examine changes in self
reported medication use by a complete birth cohort of young adults. Details of
medications taken during the previous two weeks at age 38 are compared to similar
data collected at ages 32 and 26, and by gender. Major drug categories are
examined. General use profiles and medicine-types are considered in light of our
interest in understanding the formation of the young and middle-aging
'pharmaceutical person' - where one's embodied experience is frequently and
normally mediated by pharmaceutical interventions having documented benefit/risk
outcomes.
PMID- 29349272
TI - Why is parental lifespan linked to children's chances of reaching a high age? A
transgenerational hypothesis.
AB - Purpose: Transgenerational determinants of longevity are poorly understood. We
used data from four linked generations (G0, G1, G2 and G3) of the Uppsala Birth
Cohort Multigeneration Study to address this issue. Methods: Mortality in G1 (N =
9565) was followed from 1961-2015 and analysed in relation to tertiles of their
parents' (G0) age-at-death using Cox regression. Parental social class and
marital status were adjusted for in the analyses, as was G1's birth order and
adult social class. For an almost entirely deceased segment of G1 (n = 1149),
born 1915-1917, we compared exact age-at-death with G0 parents' age-at-death.
Finally, we explored 'resilience' as a potentially important mechanism for
intergenerational transmission of longevity, using conscript information from
psychological interviews of G2 and G3 men. Results: G0 men's and women's ages-at
death were independently associated with G1 midlife and old age mortality. This
association was robust and minimally reduced when G0 and G1 social class were
adjusted for. We observed an increased lifespan in all social groups. Median
difference in age-at-death for sons compared to fathers was + 3.9 years, and +
6.9 years for daughters compared to mothers.Parents' and maternal grandmother's
longevity were associated with resilience in subsequent generations. Resilience
scores of G2 men were also associated with those of their G3 sons and with their
own mortality in midlife. Conclusions: The chance of reaching a high age is
transmitted from parents to children in a modest, but robust way. Longevity
inheritance is paralleled by the inheritance of individual resilience. Individual
resilience, we propose, develops in the first part of life as a response to
adversity and early experience in general. This gives rise to a transgenerational
pathway, distinct from social class trajectories. A theory of longevity
inheritance should bring together previous thinking around general
susceptibility, frailty and resilience with new insights from epigenetics and
social epidemiology.
PMID- 29349273
TI - The contribution of three dimensions of allostatic load to racial/ethnic
disparities in poor/fair self-rated health.
AB - Objective: This study evaluates whether different dimensions of physiological
dysregulation, modeled individually rather than additively mediate racial/ethnic
disparities in self-reported health. Methods: Using data from the National Health
and Nutrition Examination Survey (2005-2010) and the Karlson, Hold, and Breen
(KHB) mediation model, this paper explores what operationalization of biomarker
data most strongly mediate racial/ethnic disparities in poor/fair self-rated
health (SRH) among adults in the United States, net of demographic,
socioeconomic, behavioral, and medication controls. Results: Non-Hispanic blacks
and Hispanics had significantly higher odds of reporting poor/fair self-rated
health in comparison to non-Hispanic whites. Operationalizations of allostatic
load that disaggregate three major dimensions of physiological dysregulation
mediate racial/ethnic disparities strongly between non-Hispanic blacks and non
Hispanic whites, but not between Hispanics and non-Hispanic whites.
Disaggregating these dimensions explains racial/ethnic disparities in poor/fair
SRH better than the continuous score. Analyses on sex-specific disparities
indicate differences in how individual dimensions of allostatic load contribute
to racial/ethnic disparities in poor/fair SRH differently. All individual
dimensions are strong determinants of poor/fair SRH for males. In contrast, for
females, the only dimension that is significantly associated with poor/fair SRH
is inflammation. For the analytic sample, additive biomarker scores fit the data
as well or better than other approaches, suggesting that this approach is most
appropriate for explaining individual differences. However, in sex-specific
analyses, the interactive approach models fit the data best for men and women.
Conclusions: Future researchers seeking to explain racial/ethnic disparities in
full or sex-stratified samples should consider disaggregating allostatic load by
dimension.
PMID- 29349274
TI - Long-run effects of early childhood exposure to cholera on final height: Evidence
from industrializing Japan.
AB - Pandemic cholera is one of the most topical and urgent issues in many developing
countries. However, although a growing body of research has shown the negative
long-run effects of infectious disease exposure on human health, the long-run
influences of early childhood exposure to cholera have thus far been
understudied. To bridge this gap in the body of knowledge, we draw both on new
data describing adult height from 1899 to 1910 from comprehensive official
Japanese army records and on data recording the regional variation in the
intensity of cholera pandemics. By using a difference-in-differences estimation
strategy, we find that exposure to pandemic cholera had stunting effects on the
final height of men at that time. Our estimates also suggest that early-infancy
exposure to cholera seems to have a stronger long-run effect on adult height than
late-infancy exposure.
PMID- 29349275
TI - Living with parents or grandparents increases social capital and survival: 2014
General Social Survey-National Death Index.
AB - Introduction: After nearly a century-long trend toward single-family living
arrangements, people in wealthy nations are increasingly living in multi
generational households. Multi-generational living arrangements can, in theory,
increase psychological, social, and financial capital-factors associated with
improvements in health and longevity. Methods: We conducted a survival analysis
using the 2014 General Social Survey-National Death Index, a prospective multi
year survey. We explored whether single generational living arrangements were
associated with a higher risk of mortality than multi-generational living
arrangements. Results: We explored this association for different groups (e.g.,
the foreign-born and those with high self-reported stress in family
relationships). Healthy subjects who live in two-generation households were found
to have lower premature mortality (hazard ratio 0.9, 95% confidence interval =
0.82, 0.99). Otherwise, we found little evidence that living arrangements matter
for the respondents' risk of premature mortality. Conclusions: Healthy people
living in two-generation households have longer survival than healthy people
living on their own.
PMID- 29349276
TI - Examining individual, interpersonal, and environmental influences on children's
physical activity levels.
AB - The purpose of this study was to explore individual-level socio-demographic
factors and interpersonal-level factors related to social support, as well as the
potential role of neighborhood and school environments that may influence the
physical activity (PA) levels of children (ages 9-11). Child and parent
questionnaires included individual and interpersonal factors, and PA behaviour.
Home postal codes were used to determine the neighbourhood the child resides
within, as well as their geographic accessibility to recreation opportunities.
The models were assessed using a series of cross-classified random-intercept
multi-level regression models as children's PA may be affected by both the school
they attend and the neighbourhood in which they live. In the unadjusted model, PA
varied significantly across school environments (gamma = 0.023; CI: 0.003-0.043),
but not across neighbourhoods (gamma = 0.007; CI: -0.008 to 0.021). Boys were
found to be more active compared to girls (b = 0.183; CI: 0.092-0.275), while the
level of PA was lower for children whose fathers achieved post-secondary
education (b = - 0.197; CI: -0.376 to 0.018) than for those whose parents
completed only high school. The addition of the individual-level correlates did
not have a substantial effect on level 2 variances and the level 2 variance
associated with school environment remained statistically significant. At the
interpersonal level, children's perception of parental support (b = 0.117; CI:
0.091-0.143) and peer support (b = 0.111; CI: 0.079-0.142) were positively
related to PA. The level 2 variance for the school environment became
statistically non-significant when the interpersonal factors were added to the
model. At the environmental level, geographic accessibility did not have a
significant association with PA and they did not significantly affect level 1 or
2 variance. As many children do not accrue sufficient levels of PA, identifying
modifiable determinants is necessary to develop effective strategies to increase
PA.
PMID- 29349277
TI - Patterns of poverty exposure and children's trajectories of externalizing and
internalizing behaviors.
AB - Using data from the Child Supplement of the National Longitudinal Survey of
Youth, we compare trajectories of externalizing and internalizing behaviors among
children exposed to five patterns of poverty from birth to age 14: always or
never poor - stable patterns; a single transition into or out of poverty, or
repeated fluctuations in and out of poverty - changing patterns. We also examine
how low maternal education and single parenthood interact with these poverty
exposures to compound their adverse effects. Finally, we compare the magnitude of
effects associated with the patterns of poverty exposure, as well as their
interactions with low maternal education and single parenthood, on trajectories
of externalizing and internalizing behaviors to determine if they are
significantly different. Results reveal that initial levels and rates of change
in children's trajectories of externalizing and internalizing behaviors are
similar across the three changing patterns of poverty exposure, leading us to
combine them into a single group representing intermittent poverty. Initial
disparities between children who are never poor and their counterparts who are
always or intermittently poor are constant over time for internalizing behaviors
and grow in magnitude for externalizing behaviors. The cumulative negative effect
of poverty exposure over time is stronger for externalizing vs. internalizing
behaviors. Low maternal education compounds the adverse effects of persistent
poverty, an effect that is similar for externalizing and internalizing behaviors.
PMID- 29349278
TI - Machine learning approaches to the social determinants of health in the health
and retirement study.
AB - Background: Social and economic factors are important predictors of health and of
recognized importance for health systems. However, machine learning, used
elsewhere in the biomedical literature, has not been extensively applied to study
relationships between society and health. We investigate how machine learning may
add to our understanding of social determinants of health using data from the
Health and Retirement Study. Methods: A linear regression of age and gender, and
a parsimonious theory-based regression additionally incorporating income, wealth,
and education, were used to predict systolic blood pressure, body mass index,
waist circumference, and telomere length. Prediction, fit, and interpretability
were compared across four machine learning methods: linear regression, penalized
regressions, random forests, and neural networks. Results: All models had poor
out-of-sample prediction. Most machine learning models performed similarly to the
simpler models. However, neural networks greatly outperformed the three other
methods. Neural networks also had good fit to the data (R2 between 0.4-0.6,
versus <0.3 for all others). Across machine learning models, nine variables were
frequently selected or highly weighted as predictors: dental visits, current
smoking, self-rated health, serial-seven subtractions, probability of receiving
an inheritance, probability of leaving an inheritance of at least $10,000, number
of children ever born, African-American race, and gender. Discussion: Some of the
machine learning methods do not improve prediction or fit beyond simpler models,
however, neural networks performed well. The predictors identified across models
suggest underlying social factors that are important predictors of biological
indicators of chronic disease, and that the non-linear and interactive
relationships between variables fundamental to the neural network approach may be
important to consider.
PMID- 29349279
TI - Parental population exposure to historical socioeconomic and political periods
and grand-child's birth weight in the Lifeways Cross-Generation Cohort Study in
the Republic of Ireland.
AB - Exposure to deprived socioeconomic conditions during the peri-conception and
early childhood periods can have a negative long-term impact on individuals'
health and that of their progeny. We aimed to examine whether relatives' birth
period affected index-child (grand-child) birthweight status in the Lifeways
Cross-Generation Cohort in the Republic of Ireland. Participants were 943 mothers
and offspring, 890 fathers, 938 maternal grandmothers (MGM), 700 maternal
grandfathers (MGF) 537 paternal grandmothers (PGM) and 553 paternal grandfathers
(PGF). Index-child's birthweight was sex-for-gestational age standardised (UK1990
population), and then classified into low birthweight (<=10th percentile) and
high-birthweight (>=90th percentile) and compared against normal-birthweight
(>10th to <90th percentiles). Four adult birth periods were considered: The Free
State (FS, 1916-1938); Emergency Act (EA, 1939-1946); Post-World War-II Baby-Boom
(PWWII-BB, 1947-1964); and Modern Ireland (MI, 1964 onwards). Logistic regression
was used to assess the crude and adjusted relationship between index-child's
birthweight status and relatives' birth periods. Overall, there were 8.7% (n=82)
index-children in the low-birthweight category, 77.9% (n=735) and 13.4% (n=126)
within the normal and high birthweight groups respectively. Index-children whose
mothers were born during the PWWII-BB had higher birthweight infants (Crude
OR(COR)=1.81 (1.08-3.03) which remained the case only for male index-children
when adjusted for co-variables (Adjusted OR(AOR)=4.61(1.71-12.42)). Parents'
combined PWWII-BB birth period was positively associated with male index-child
higher birthweight, even adjusted for maternal characteristics (AOR=4.60(1.69
12.50)). MGFs born during the EA were more likely to have grandchildren with low
birthweight after adjustment for maternal characteristics (AOR=2.45(1.03-5.85)),
particularly for female index-children (AOR=4.74(1.16-19.25)). Both PGMs and PGFs
born during the FS period had higher birthweight grandchildren, adjusted for
maternal-related co-variables (PGM, AOR=3.23(1.21-8.63); PGF, AOR=3.93(1.11
13.96)), with the effect of PGM more evident in her granddaughter (AOR=6.53(1.25
34.04)). In conclusion, there is some evidence that period of grandparental birth
is associated with their grandchildren's birthweights, suggesting that
transgenerational exposures may be particular to historical context, meriting
further exploration.
PMID- 29349280
TI - Food insecurity and family structure in Nigeria.
AB - The article explores a series of questions and hypotheses related to polygynous
family structures and both household and individual-level food security outcomes,
using the World Bank Living Standards Measurement Survey data from Nigeria,
collected in 2011, 2013 and 2015. A Correlated Random Effects (CRE) model is used
to examine the relationship between polygyny and household-level food security,
and the degree to which it is mediated by household wealth, size, and livelihood.
A Household Fixed Effect model is employed to explore whether a mother's status
as monogamous versus polygynous relates systematically to her child's health, and
also whether child outcomes of senior wives are better than outcomes of junior
wives within polygynous households. At the household level, polygynous households
are found to have better food security outcomes than monogamous households with
differences in household composition and agricultural livelihood as potential
explanatory mechanisms. At the individual level, however, children of polygynous
mothers have worse nutrition outcomes than children of monogamous mothers in the
long run. Within polygynous households, children of junior wives appear to have
better nutritional outcomes in the long run, compared to children of more senior
wives.
PMID- 29349281
TI - Work disability in the United States, 1968-2015: Prevalence, duration, recovery,
and trends.
AB - The United States workforce is aging. At the same time more people have chronic
conditions, for longer periods. Given these trends the importance of work
disability, physical or nervous problems that limit a person's type or amount of
work, is increasing. No research has examined transitions among multiple levels
of work disability, recovery from work disability, or trends. Limited research
has focused on work disability among African Americans and Hispanics, or
separately for women and men. We examined these areas using data from 30,563
adults in the 1968-2015 Panel Study of Income Dynamics. We estimated annual
probabilities of work disability, recovery, and death with multinomial logistic
Markov models. Microsimulations accounting for age and education estimated
outcomes for African American, Hispanic, and non-Hispanic white women and men.
Results from these nationally representative data suggested that the majority of
Americans experience work disability during working life. Most spells ended with
recovery or reduced severity. Among women, African Americans and Hispanics had
less moderate and severe work disability than whites. Among men, African
Americans became severely work disabled more often than whites, recovered from
severe spells more often and had shorter severe spells, yet had more severe work
disability at age 65. Hispanic men were more likely to report at least one spell
of severe work disability than whites; they also had substantially more recovery
from severe work disability, and a lower percentage of working years with work
disability. Among African Americans and Hispanics, men were considerably more
likely than women to have severe work disability at age 65. Work disability
declined significantly across the study period for all groups. Although work
disability has declined over several decades, it remains common. Results suggest
that the majority of work disability spells end with recovery, underscoring the
importance of rehabilitation and workplace accommodation.
PMID- 29349282
TI - Does non-standard work mean non-standard health? Exploring links between non
standard work schedules, health behavior, and well-being.
AB - The last century has seen dramatic shifts in population work circumstances,
leading to an increasing normalization of non-standard work schedules (NSWSs),
defined as non-daytime, irregular hours. An ever-growing body of evidence links
NSWSs to a host of non-communicable chronic conditions; yet, these associations
primarily concentrate on the physiologic mechanisms created by circadian
disruption and insufficient sleep. While important, not all NSWSs create such
chronobiologic disruption, and other aspects of working time and synchronization
could be important to the relationships between work schedules and chronic
disease. Leveraging survey data from Project EAT, a population-based study with
health-related behavioral and psychological data from U.S. adults aged 25-36
years, this study explored the risks for a broad range of less healthful
behavioral and well-being outcomes among NSWS workers compared to standard
schedule workers (n = 1402). Variations across different NSWSs (evening,
night/rotating, and irregular schedules) were also explored. Results indicated
that, relative to standard schedule workers, workers with NSWSs are at increased
risk for non-optimal sleep, substance use, greater recreational screen time,
worse dietary practices, obesity, and depression. There was minimal evidence to
support differences in relative risks across workers with different types of
NSWSs. The findings provide insight into the potential links between NSWSs and
chronic disease and indicate the relevancy social disruption and daily health
practices may play in the production of health and well-being outcomes among
working populations.
PMID- 29349283
TI - Is self-rated health in adolescence a predictor of prescribed medication in
adulthood? Findings from the Nord Trondelag Health Study and the Norwegian
Prescription Database.
AB - Self-rated health (SRH) is a commonly used health indicator predicting morbidity
and mortality in a range of populations. However, the relationship between SRH
and medication is not well established. The aim of this study was to examine
adolescent SRH as a predictor for prescribed medication later in young adulthood.
Eighteen years' prospective data from the Nord-Trondelag Health Study (HUNT) and
the Norwegian Prescription Database (NorPD) were analyzed. Baseline data,
gathered from 8982 adolescents (mean age 16.0 years) in the Young-HUNT I survey
(1995-1997), were linked to individual data from NorPD, including information on
all medications prescribed in 2013-2014. Gender-stratified negative binomial
regression models were used to investigate the association between SRH and
medication, also adjusted for age, baseline self-reported medicine use, physical
and mental disability, smoking, and physical activity. Based on the Anatomical
Therapeutic Chemical (ATC) Classification System, total consumption and
consumption related to various ATC groups were examined. The adjusted analyses
showed a dose-response relationship for females, with poorer SRH predicting
higher average medication for both total consumption and for the ATC groups
"Musculoskeletal system" (M), "Nervous system" (N; Analgesics (N02), Opioids
(N02A)) and "Respiratiory system" (R). The predictive power of SRH, as well as
the role of the adjustment factors, varies by gender and drug groups. This
knowledge is important in order to identify risks for later disease and to
capture pathological changes before and beyond the disease diagnosis, potentially
preventing morbidity in the adult population.
PMID- 29349284
TI - The relationship between physical functional limitations, and psychological
distress: Considering a possible mediating role of pain, social support and sense
of mastery.
AB - The aim of this study was to examine associations between selected physical
functional limitations related to performing daily activities and psychological
distress. We also aimed to investigate if these associations vary across age
(moderation), and to explore pain, sense of mastery and social support as
potential moderators and mediators. The study was based on pooled data from two
rounds (2008 and 2012) of a Norwegian nationally representative cross-sectional
health survey (N = 8520) including individuals aged >= 16 years (Age groups = 16
44 and >= 45 years). Physical functional limitations comprised decreased ability
to: i) climb stairs, ii) carry objects, or iii) both. Psychological distress was
measured as anxiety and depressive symptoms occurring separately or in
combination (CAD). Of respondents reporting physical functional limitations, 8
14% reported depressive symptoms, 5-7% anxiety symptoms, and 13-28% reported CAD.
Physical functional limitations were significantly associated with all three
forms of psychological distress, particularly among individuals 16-44 years, and
were more strongly related to CAD than to anxiety or depression occurring
separately. The association with CAD was twice as strong when both types of
physical functional limitations were present. Pain, sense of mastery and social
support were significant modifiers of depression, whereas all three were
significant mediators of the relationship between physical functional limitations
and anxiety, depression and CAD. Sense of mastery mediated the relationship
between physical functional limitations and CAD, but most strongly among those 16
44 years. Social support was only a significant mediator among those [Formula:
see text] 45 years. Close associations between physical functional limitations
and psychological distress highlight special needs among individuals experiencing
daily functional limitations. The results also suggest that pain, low social
support, and low sense of mastery may contribute to aggravate psychological
distress.
PMID- 29349285
TI - A smart-phone intervention to address mental health stigma in the construction
industry: A two-arm randomised controlled trial.
AB - Background: High levels of self-stigma are associated with a range of adverse
mental health, treatment, and functional outcomes. This prospective study
examined the effects of an electronic mental health stigma reduction intervention
on self-stigma (self-blame, shame, and help-seeking inhibition) among male
construction workers in Australia. Method: Male construction workers (N = 682)
were randomly assigned to receive either the intervention condition or the wait
list control over a six-week period. Self-stigma was assessed using the Self
Stigma of Depression Scale at post-intervention. We conducted linear regression
to assess the effectiveness of the intervention on self-stigma, adjusting for
relevant covariates. Results: Self-stigma was relatively low in the sample. The
intervention had no significant effect on self-stigma, after adjusting for
confounders. There were reductions in stigma in both the intervention and control
groups at 6-week follow-up. Process evaluation indicated that participants
generally enjoyed the program and felt that it was beneficial to their mental
health. Conclusions: These observations underscore the need for further research
to elucidate understanding of the experience of self-stigma among employed males.
PMID- 29349286
TI - Exercise self-efficacy in adults with congenital heart disease.
AB - Background: Physical activity improves health, exercise tolerance and quality of
life in adults with congenital heart disease (CHD), and exercise training is in
most patients a high-benefit low risk intervention. However, factors that
influence the confidence to perform exercise training, i.e. exercise self
efficacy (ESE), in CHD patients are virtually unknown. We aimed to identify
factors related to low ESE in adults with CHD, and potential strategies for being
physically active. Methods: Seventy-nine adults with CHD; 38 with simple lesions
(16 women) and 41 with complex lesions (17 women) with mean age 36.7 +/- 14.6
years and 42 matched controls were recruited. All participants completed
questionnaires on ESE and quality of life, carried an activity monitor
(Actiheart) during four consecutive days and performed muscle endurance tests.
Results: ESE in patients was categorised into low, based on the lowest quartile
within controls, (<= 29 points, n = 34) and high (> 29 points, n = 45). Patients
with low ESE were older (42.9 +/- 15.1 vs. 32.0 +/- 12.4 years, p = 0.001), had
more complex lesions (65% vs. 42%, p = 0.05) more often had New York Heart
Association functional class III (24% vs. 4%, p = 0.01) and performed fewer
shoulder flexions (32.5 +/- 15.5 vs. 47.7 +/- 25.0, p = 0.001) compared with
those with high ESE. In a logistic multivariate model age (OR; 1.06, 95% CI 1.02
1.10), and number of shoulder flexions (OR; 0.96, 95% CI 0.93-0.99) were
associated with ESE. Conclusion: In this study we show that many adults with CHD
have low ESE. Age is an important predictor of low ESE and should, therefore, be
considered in counselling patients with CHD. In addition, muscle endurance
training may improve ESE, and thus enhance the potential for being physically
active in this population.
PMID- 29349287
TI - Barriers to Diet and Exercise among Nepalese Type 2 Diabetic Patients.
AB - This study aims to identify the modifiable barriers encountered by type 2
diabetic patients in Nepal to achieving their recommended dietary and exercise
advice. A cross-sectional study was conducted among 197 type 2 diabetic patients,
attending a diabetic clinic. Binary logistic regression models were used to
identify perceived barriers. About 41% and 46% of the participants were
noncompliant to diet and exercise advice, respectively; only 35.5% the
participants were compliant to both. Perceived social acceptability (OR = 0.14;
95% CI: 0.03-0.58) and reminder to action (OR = 2.77; 95% CI: 1.38-5.53) were
associated with noncompliance to diet. Most of the barriers to diet were related
to taste, feast and festivals, lack of knowledge, and availability of healthy
options. Self-efficacy (OR = 0.09; 95% CI: 0.02-0.34) and social acceptability
(OR = 0.12; 95% CI: 0.04-0.34) were significant predictors of noncompliance to
exercise. The supportive role of children and spouse and the opposing role of
friends and relatives were important for compliance to both. A misconception on
diabetes severity, effectiveness of healthy lifestyle, and exercise timing was
prevalent among the study participants. Addressing the modifiable barriers
identified in this study is essential for successful diabetes management in
Nepal.
PMID- 29349288
TI - The In Vivo Dynamics of HIV Infection with the Influence of Cytotoxic T
Lymphocyte Cells.
AB - The in vivo dynamics of HIV infection, the infection mechanism, the cell types
infected, and the role played by the cytotoxic cells are poorly understood. This
paper uses mathematical modelling as a tool to investigate and analyze the immune
system dynamics in the presence of HIV infection. We formulate a six-dimensional
model of nonlinear ordinary differential equations derived from known biological
interaction mechanisms between the immune cells and the HIV virions. The
existence and uniqueness as well as positivity and boundedness of the solutions
to the differential equations are proved. Furthermore, the disease-free
reproduction number is derived and the local asymptotic stability of the model
investigated. In addition, numerical analysis is carried out to illustrate the
importance of having R0 < 1. Lastly, the biological dynamics of HIV in vivo
infection are graphically represented. The results indicate that, at acute
infection, the cytotoxic T-cells play a paramount role in reducing HIV viral
replication. In addition, the results emphasize the importance of developing
controls, interventions, and management policies that when implemented would lead
to viral suppression during acute infection.
PMID- 29349289
TI - Mixed Neurodevelopmental and Neurodegenerative Pathology in Nhe6-Null Mouse Model
of Christianson Syndrome.
AB - Christianson syndrome (CS) is an X-linked disorder resulting from loss-of
function mutations in SLC9A6, which encodes the endosomal Na+/H+ exchanger 6
(NHE6). Symptoms include early developmental delay, seizures, intellectual
disability, nonverbal status, autistic features, postnatal microcephaly, and
progressive ataxia. Neuronal development is impaired in CS, involving defects in
neuronal arborization and synaptogenesis, likely underlying diminished brain
growth postnatally. In addition to neurodevelopmental defects, some reports have
supported neurodegenerative pathology in CS with age. The objective of this study
was to determine the nature of progressive changes in the postnatal brain in Nhe6
null mice. We examined the trajectories of brain growth and atrophy in mutant
mice from birth until very old age (2 yr). We report trajectories of volume
changes in the mutant that likely reflect both brain undergrowth as well as
tissue loss. Reductions in volume are first apparent at 2 mo, particularly in the
cerebellum, which demonstrates progressive loss of Purkinje cells (PCs). We
report PC loss in two distinct Nhe6-null mouse models. More widespread reductions
in tissue volumes, namely, in the hippocampus, striatum, and cortex, become
apparent after 2 mo, largely reflecting delays in growth with more limited tissue
losses with aging. Also, we identify pronounced glial responses, particularly in
major fiber tracts such as the corpus callosum, where the density of activated
astrocytes and microglia are substantially increased. The prominence of the glial
response in axonal tracts suggests a primary axonopathy. Importantly, therefore,
our data support both neurodevelopmental and degenerative mechanisms in the
pathobiology of CS.
PMID- 29349290
TI - A Novel Neuroprotective Mechanism for Lithium That Prevents Association of the
p75NTR-Sortilin Receptor Complex and Attenuates proNGF-Induced Neuronal Death In
Vitro and In Vivo.
AB - Neurotrophins play critical roles in the survival, maintenance and death of
neurons. In particular, proneurotrophins have been shown to mediate cell death
following brain injury induced by status epilepticus (SE) in rats. Previous
studies have shown that pilocarpine-induced seizures lead to increased levels of
proNGF, which binds to the p75NTR-sortilin receptor complex to elicit apoptosis.
A screen to identify compounds that block proNGF binding and uptake into cells
expressing p75 and sortilin identified lithium citrate as a potential inhibitor
of proNGF and p75NTR-mediated cell death. In this study, we demonstrate that low,
submicromolar doses of lithium citrate effectively inhibited proNGF-induced cell
death in cultured neurons and protected hippocampal neurons following pilocarpine
induced SE in vivo. We analyzed specific mechanisms by which lithium citrate
afforded neuroprotection and determined that lithium citrate prevented the
association and internalization of the p75NTR-sortilin receptor complex. Our
results demonstrate a novel mechanism by which low-dose treatments of lithium
citrate are effective in attenuating p75NTR-mediated cell death in vitro and in
vivo.
PMID- 29349291
TI - Spontaneous Infraslow Fluctuations Modulate Hippocampal EPSP-PS Coupling.
AB - Extensive trial-to-trial variability is a hallmark of most behavioral, cognitive,
and physiological processes. Spontaneous brain activity (SBA), a ubiquitous
phenomenon that coordinates levels and patterns of neuronal activity throughout
the brain, may contribute to this variability by dynamically altering neuronal
excitability. In freely-behaving male rats, we observed extensive variability of
the hippocampal evoked response across 28-min recording periods despite
maintaining constant stimulation parameters of the medial perforant path. This
variability was related to antecedent SBA: increases in low-frequency (0.5-9 Hz)
and high-frequency (40.25-100 Hz) band-limited power (BLP) in the 4-s preceding
stimulation were associated with decreased slope of the field EPSP (fEPSP) and
increased population spike (PS) amplitude. These fluctuations in SBA and evoked
response magnitude did not appear stochastic but rather exhibited coordinated
activity across infraslow timescales (0.005-0.02 Hz). Specifically, infraslow
fluctuations in high- and low-frequency BLP were antiphase with changes in fEPSP
slope and in phase with changes in PS amplitude. With these divergent effects on
the fEPSP and PS, infraslow SBA ultimately modulates EPSP-PS coupling and thereby
enables hippocampal circuitry to generate heterogeneous outputs from identical
inputs. Consequently, infraslow SBA appears well suited to dynamically alter
sensory selection and information processing and highlights the fundamental role
of endogenous neuronal activity for shaping the brain's response to incoming
stimuli.
PMID- 29349292
TI - Membrane insertion of-and membrane potential sensing by-semiconductor voltage
nanosensors: Feasibility demonstration.
AB - We developed membrane voltage nanosensors that are based on inorganic
semiconductor nanoparticles. We provide here a feasibility study for their
utilization. We use a rationally designed peptide to functionalize the
nanosensors, imparting them with the ability to self-insert into a lipid membrane
with a desired orientation. Once inserted, these nanosensors could sense membrane
potential via the quantum confined Stark effect, with a single-particle
sensitivity. With further improvements, these nanosensors could potentially be
used for simultaneous recording of action potentials from multiple neurons in a
large field of view over a long duration and for recording electrical signals on
the nanoscale, such as across one synapse.
PMID- 29349293
TI - Experimenter gender and replicability in science.
AB - There is a replication crisis spreading through the annals of scientific inquiry.
Although some work has been carried out to uncover the roots of this issue, much
remains unanswered. With this in mind, this paper investigates how the gender of
the experimenter may affect experimental findings. Clinical trials are regularly
carried out without any report of the experimenter's gender and with dubious
knowledge of its influence. Consequently, significant biases caused by the
experimenter's gender may lead researchers to conclude that therapeutics or other
interventions are either overtreating or undertreating a variety of conditions.
Bearing this in mind, this policy paper emphasizes the importance of reporting
and controlling for experimenter gender in future research. As backdrop, it
explores what we know about the role of experimenter gender in influencing
laboratory results, suggests possible mechanisms, and suggests future areas of
inquiry.
PMID- 29349294
TI - Changes in seasonal snow water equivalent distribution in High Mountain Asia
(1987 to 2009).
AB - Snow meltwaters account for most of the yearly water budgets of many catchments
in High Mountain Asia (HMA). We examine trends in snow water equivalent (SWE)
using passive microwave data (1987 to 2009). We find an overall decrease in SWE
in HMA, despite regions of increased SWE in the Pamir, Kunlun Shan, Eastern
Himalaya, and Eastern Tien Shan. Although the average decline in annual SWE
across HMA (contributing area, 2641 * 103 km2) is low (average, -0.3%), annual
SWE losses conceal distinct seasonal and spatial heterogeneities across the study
region. For example, the Tien Shan has seen both strong increases in winter SWE
and sharp declines in spring and summer SWE. In the majority of catchments, the
most negative SWE trends are found in mid-elevation zones, which often correspond
to the regions of highest snow-water storage and are somewhat distinct from
glaciated areas. Negative changes in SWE storage in these mid-elevation zones
have strong implications for downstream water availability.
PMID- 29349295
TI - A Triassic-Jurassic window into the evolution of Lepidoptera.
AB - On the basis of an assemblage of fossilized wing scales recovered from latest
Triassic and earliest Jurassic sediments from northern Germany, we provide the
earliest evidence for Lepidoptera (moths and butterflies). The diverse scales
confirm a (Late) Triassic radiation of lepidopteran lineages, including the
divergence of the Glossata, the clade that comprises the vast multitude of extant
moths and butterflies that have a sucking proboscis. The microfossils extend the
minimum calibrated age of glossatan moths by ca. 70 million years, refuting
ancestral association of the group with flowering plants. Development of the
proboscis may be regarded as an adaptive innovation to sucking free liquids for
maintaining the insect's water balance under arid conditions. Pollination drops
secreted by a variety of Mesozoic gymnosperms may have been non-mutualistically
exploited as a high-energy liquid source. The early evolution of the Lepidoptera
was probably not severely interrupted by the end-Triassic biotic crisis.
PMID- 29349296
TI - Unlocking data sets by calibrating populations of models to data density: A study
in atrial electrophysiology.
AB - The understanding of complex physical or biological systems nearly always
requires a characterization of the variability that underpins these processes. In
addition, the data used to calibrate these models may also often exhibit
considerable variability. A recent approach to deal with these issues has been to
calibrate populations of models (POMs), multiple copies of a single mathematical
model but with different parameter values, in response to experimental data. To
date, this calibration has been largely limited to selecting models that produce
outputs that fall within the ranges of the data set, ignoring any trends that
might be present in the data. We present here a novel and general methodology for
calibrating POMs to the distributions of a set of measured values in a data set.
We demonstrate our technique using a data set from a cardiac electrophysiology
study based on the differences in atrial action potential readings between
patients exhibiting sinus rhythm (SR) or chronic atrial fibrillation (cAF) and
the Courtemanche-Ramirez-Nattel model for human atrial action potentials. Not
only does our approach accurately capture the variability inherent in the
experimental population, but we also demonstrate how the POMs that it produces
may be used to extract additional information from the data used for calibration,
including improved identification of the differences underlying stratified data.
We also show how our approach allows different hypotheses regarding the
variability in complex systems to be quantitatively compared.
PMID- 29349297
TI - Organic matter in extraterrestrial water-bearing salt crystals.
AB - Direct evidence of complex prebiotic chemistry from a water-rich world in the
outer solar system is provided by the 4.5-billion-year-old halite crystals hosted
in the Zag and Monahans (1998) meteorites. This study offers the first
comprehensive organic analysis of the soluble and insoluble organic compounds
found in the millimeter-sized halite crystals containing brine inclusions and
sheds light on the nature and activity of aqueous fluids on a primitive parent
body. Associated with these trapped brines are organic compounds exhibiting wide
chemical variations representing organic precursors, intermediates, and reaction
products that make up life's precursor molecules such as amino acids. The organic
compounds also contain a mixture of C-, O-, and N-bearing macromolecular carbon
materials exhibiting a wide range of structural order, as well as aromatic,
ketone, imine, and/or imidazole compounds. The enrichment in 15N is comparable to
the organic matter in pristine Renazzo-type carbonaceous chondrites, which
reflects the sources of interstellar 15N, such as ammonia and amino acids. The
amino acid content of the Zag halite deviates from the meteorite matrix,
supporting an exogenic origin of the halite, and therefore, the Zag meteorite
contains organics synthesized on two distinct parent bodies. Our study suggests
that the asteroidal parent body where the halite precipitated, potentially
asteroid 1 Ceres, shows evidence for a complex combination of biologically and
prebiologically relevant molecules.
PMID- 29349298
TI - Direct measurements of DOCO isomers in the kinetics of OD + CO.
AB - Quantitative and mechanistically detailed kinetics of the reaction of hydroxyl
radical (OH) with carbon monoxide (CO) have been a longstanding goal of
contemporary chemical kinetics. This fundamental prototype reaction plays an
important role in atmospheric and combustion chemistry, motivating studies for
accurate determination of the reaction rate coefficient and its pressure and
temperature dependence at thermal reaction conditions. This intricate dependence
can be traced directly to details of the underlying dynamics (formation,
isomerization, and dissociation) involving the reactive intermediates cis- and
trans-HOCO, which can only be observed transiently. Using time-resolved frequency
comb spectroscopy, comprehensive mechanistic elucidation of the kinetics of the
isotopic analog deuteroxyl radical (OD) with CO has been realized. By monitoring
the concentrations of reactants, intermediates, and products in real time, the
branching and isomerization kinetics and absolute yields of all species in the OD
+ CO reaction are quantified as a function of pressure and collision partner.
PMID- 29349299
TI - Limited contribution of ancient methane to surface waters of the U.S. Beaufort
Sea shelf.
AB - In response to warming climate, methane can be released to Arctic Ocean sediment
and waters from thawing subsea permafrost and decomposing methane hydrates.
However, it is unknown whether methane derived from this sediment storehouse of
frozen ancient carbon reaches the atmosphere. We quantified the fraction of
methane derived from ancient sources in shelf waters of the U.S. Beaufort Sea, a
region that has both permafrost and methane hydrates and is experiencing
significant warming. Although the radiocarbon-methane analyses indicate that
ancient carbon is being mobilized and emitted as methane into shelf bottom
waters, surprisingly, we find that methane in surface waters is principally
derived from modern-aged carbon. We report that at and beyond approximately the
30-m isobath, ancient sources that dominate in deep waters contribute, at most,
10 +/- 3% of the surface water methane. These results suggest that even if there
is a heightened liberation of ancient carbon-sourced methane as climate change
proceeds, oceanic oxidation and dispersion processes can strongly limit its
emission to the atmosphere.
PMID- 29349300
TI - Tensile forces drive a reversible fibroblast-to-myofibroblast transition during
tissue growth in engineered clefts.
AB - Myofibroblasts orchestrate wound healing processes, and if they remain activated,
they drive disease progression such as fibrosis and cancer. Besides growth factor
signaling, the local extracellular matrix (ECM) and its mechanical properties are
central regulators of these processes. It remains unknown whether transforming
growth factor-beta (TGF-beta) and tensile forces work synergistically in up
regulating the transition of fibroblasts into myofibroblasts and whether
myofibroblasts undergo apoptosis or become deactivated by other means once tissue
homeostasis is reached. We used three-dimensional microtissues grown in vitro
from fibroblasts in macroscopically engineered clefts for several weeks and found
that fibroblasts transitioned into myofibroblasts at the highly tensed growth
front as the microtissue progressively closed the cleft, in analogy to closing a
wound site. Proliferation was up-regulated at the growth front, and new highly
stretched fibronectin fibers were deposited, as revealed by fibronectin
fluorescence resonance energy transfer probes. As the tissue was growing, the ECM
underneath matured into a collagen-rich tissue containing mostly fibroblasts
instead of myofibroblasts, and the fibronectin fibers were under reduced tension.
This correlated with a progressive rounding of cells from the growth front
inward, with decreased alpha-smooth muscle actin expression, YAP nuclear
translocation, and cell proliferation. Together, this suggests that the
myofibroblast phenotype is stabilized at the growth front by tensile forces, even
in the absence of endogenously supplemented TGF-beta, and reverts into a
quiescent fibroblast phenotype already 10 MUm behind the growth front, thus
giving rise to a myofibroblast-to-fibroblast transition. This is the hallmark of
reaching prohealing homeostasis.
PMID- 29349301
TI - Emergence of Kondo lattice behavior in a van der Waals itinerant ferromagnet,
Fe3GeTe2.
AB - Searching for heavy fermion (HF) states in non-f-electron systems becomes an
interesting issue, especially in the presence of magnetism, and can help explain
the physics of complex compounds. Using angle-resolved photoemission
spectroscopy, scanning tunneling microscopy, physical properties measurements,
and the first-principles calculations, we observe the HF state in a 3d-electron
van der Waals ferromagnet, Fe3GeTe2. Upon entering the ferromagnetic state, a
massive spectral weight transfer occurs, which results from the exchange
splitting. Meanwhile, the Fermi surface volume and effective electron mass are
both enhanced. When the temperature drops below a characteristic temperature T*,
heavy electrons gradually emerge with further enhanced effective electron mass.
The coexistence of ferromagnetism and HF state can be well interpreted by the
dual properties (itinerant and localized) of 3d electrons. This work expands the
limit of ferromagnetic HF materials from f- to d-electron systems and illustrates
the positive correlation between ferromagnetism and HF state in the 3d-electron
material, which is quite different from the f-electron systems.
PMID- 29349302
TI - Fast, noise-free memory for photon synchronization at room temperature.
AB - Future quantum photonic networks require coherent optical memories for
synchronizing quantum sources and gates of probabilistic nature. We demonstrate a
fast ladder memory (FLAME) mapping the optical field onto the superposition
between electronic orbitals of rubidium vapor. Using a ladder-level system of
orbital transitions with nearly degenerate frequencies simultaneously enables
high bandwidth, low noise, and long memory lifetime. We store and retrieve 1.7-ns
long pulses, containing 0.5 photons on average, and observe short-time external
efficiency of 25%, memory lifetime (1/e) of 86 ns, and below 10-4 added noise
photons. Consequently, coupling this memory to a probabilistic source would
enhance the on-demand photon generation probability by a factor of 12, the
highest number yet reported for a noise-free, room temperature memory. This paves
the way toward the controlled production of large quantum states of light from
probabilistic photon sources.
PMID- 29349303
TI - Integrated Medical Curriculum: Advantages and Disadvantages.
AB - Most curricula for medical education have been integrated horizontally and
vertically--vertically between basic and clinical sciences. The Flexnerian
curriculum has disappeared to permit integration between basic sciences and
clinical sciences, which are taught throughout the curriculum. We have proposed a
different form of integration where the horizontal axis represents the defined
learning outcomes and the vertical axis represents the teaching of the sciences
throughout the courses. We believe that a mere integration of basic and clinical
sciences is not enough because it is necessary to emphasize the importance of
humanism as well as health population sciences in medicine. It is necessary to
integrate basic and clinical sciences, humanism, and health population in the
vertical axis, not only in the early years but also throughout the curriculum,
presupposing the use of active teaching methods based on problems or cases in
small groups.
PMID- 29349304
TI - Negative Marking and the Student Physician--A Descriptive Study of Nigerian
Medical Schools.
AB - Background: There is considerable debate about the two most commonly used scoring
methods, namely, the formula scoring (popularly referred to as negative marking
method in our environment) and number right scoring methods. Although the
negative marking scoring system attempts to discourage students from guessing in
order to increase test reliability and validity, there is the view that it is an
excessive and unfair penalty that also increases anxiety. Feedback from students
is part of the education process; thus, this study assessed the perception of
medical students about negative marking method for multiple choice question (MCQ)
examination formats and also the effect of gender and risk-taking behavior on
scores obtained with this assessment method. Methods: This was a prospective
multicenter survey carried out among fifth year medical students in Enugu State
University and the University of Nigeria. A structured questionnaire was
administered to 175 medical students from the two schools, while a class test was
administered to medical students from Enugu State University. Qualitative
statistical methods including frequencies, percentages, and chi square were used
to analyze categorical variables. Quantitative statistics using analysis of
variance was used to analyze continuous variables. Results: Inquiry into
assessment format revealed that most of the respondents preferred MCQs (65.9%).
One hundred and thirty students (74.3%) had an unfavorable perception of negative
marking. Thirty-nine students (22.3%) agreed that negative marking reduces the
tendency to guess and increases the validity of MCQs examination format in
testing knowledge content of a subject compared to 108 (61.3%) who disagreed with
this assertion (chi2 = 23.0, df = 1, P = 0.000). The median score of the students
who were not graded with negative marking was significantly higher than the score
of the students graded with negative marking (P = 0.001). There was no
statistically significant difference in the risk-taking behavior between male and
female students in their MCQ answering patterns with negative marking method (P =
0.618). Conclusions: In the assessment of students, it is more desirable to adopt
fair penalties for discouraging guessing rather than excessive penalties for
incorrect answers, which could intimidate students in negative marking schemes.
There is no consensus on the penalty for an incorrect answer. Thus, there is a
need for continued research into an effective and objective assessment tool that
will ensure that the students' final score in a test truly represents their level
of knowledge.
PMID- 29349305
TI - From Introduction to Integration: Providing Community-Engaged Structure for
Interprofessional Education.
AB - Background: Training future healthcare profession students using
interprofessional education (IPE) is critical to improve quality of health care
and patient safety. Objective: The objective of this study was to implement an
IPE program and determine student satisfaction with each session, including a
clinical case requiring teams with members from each profession addressing
clinical scenarios. Subjects: The subjects of this study were students from
Athletic Training, Medicine, Nursing, Pharmacy, Physical Therapy, Physician
Assistant, Social Work, and Speech-Language Pathology. Methods: Evaluations,
administered to all participating students, consisted of Likert-style responses,
rating agreement with a series of questions, and space for descriptive comments.
Score differences for each question were compared using independent group t-tests
with a P-value of 0.05 to determine statistical significance. Results: There were
statistically higher satisfaction ratings for the problem-based learning case
when compared to less interactive sessions (P < 0.0001). Conclusion: Students
perceived benefits of the IPE program. Perceptions improved when various students
had the opportunity to work together on clinically relevant problems.
PMID- 29349307
TI - Blended Learning in Obstetrics and Gynecology Resident Education: Impact on
Resident Clinical Performance.
AB - Problem: Effects of residents' blended learning on their clinical performance
have rarely been reported. A blended learning pilot program was instituted at
Southern Illinois University School of Medicine's Obstetrics and Gynecology
program. One of the modules was chronic hypertension in pregnancy. We sought to
evaluate if the resident blended learning was transferred to their clinical
performance six months after the module. Intervention: A review of patient charts
demonstrated inadequate documentation of history, evaluation, and counseling of
patients with chronic hypertension at the first prenatal visit by Obstetrics and
Gynecology (OB/GYN) residents. A blended learning module on chronic hypertension
in pregnancy was then provided to the residents. A retrospective chart review was
then performed to assess behavioral changes in the OB/GYN residents. Context:
This intervention was carried out at the Department of Obstetrics and Gynecology,
Southern Illinois University. All 16 OB/GYN residents were enrolled in this
module as part of their educational curriculum. A query of all prenatal patients
diagnosed with chronic hypertension presenting to the OB/GYN resident clinics
four months prior to the implementation of the blended learning module (March
2015-June 2015) and six months after (July 20, 2015-February 2016) was performed.
Data were collected from outpatient charts utilizing the electronic medical
record. Data were abstracted from resident documentation at the first prenatal
visit. Outcome: The residents thought that the blended learning module was
applicable to performance improvement in the real-world setting. Patients
evaluated before (n = 10) and after (n = 7) the intervention were compared. After
the intervention, there was an increase in assessment of baseline liver enzymes,
referral for electrocardiogram, and early assessment for diabetes in the obese
patients. More patients were provided a blood pressure cuff after the module
(71.4% vs. 20%). Data were provided to the residents in an informal setting.
Discussion during this session suggested that inconsistent use of the algorithm
and incomplete documentation were reasons for the findings. Lessons Learned: This
study suggests that blended learning may be a viable tool to support sustained
changes in the performance of OB/GYN residents. Scheduled follow-up should be
employed to facilitate and ensure continued learning and behavioral changes.
PMID- 29349306
TI - Case-Based Learning and its Application in Medical and Health-Care Fields: A
Review of Worldwide Literature.
AB - Introduction: Case-based learning (CBL) is a newer modality of teaching
healthcare. In order to evaluate how CBL is currently used, a literature search
and review was completed. Methods: A literature search was completed using an
OVID(c) database using PubMed as the data source, 1946-8/1/2015. Key words used
were "Case-based learning" and "medical education", and 360 articles were
retrieved. Of these, 70 articles were selected to review for location, human
health care related fields of study, number of students, topics, delivery
methods, and student level. Results: All major continents had studies on CBL.
Education levels were 64% undergraduate and 34% graduate. Medicine was the most
frequently represented field, with articles on nursing, occupational therapy,
allied health, child development and dentistry. Mean number of students per study
was 214 (7-3105). The top 3 most common methods of delivery were live
presentation in 49%, followed by computer or web-based in 20% followed by mixed
modalities in 19%. The top 3 outcome evaluations were: survey of participants,
knowledge test, and test plus survey, with practice outcomes less frequent.
Selected studies were reviewed in greater detail, highlighting advantages and
disadvantages of CBL, comparisons to Problem-based learning, variety of fields in
healthcare, variety in student experience, curriculum implementation, and finally
impact on patient care. Conclusions: CBL is a teaching tool used in a variety of
medical fields using human cases to impart relevance and aid in connecting theory
to practice. The impact of CBL can reach from simple knowledge gains to changing
patient care outcomes.
PMID- 29349308
TI - Creating a Novel Cardiac Limited Ultrasound Exam Curriculum for Internal Medical
Residency: Four Unanticipated Tasks.
AB - Over the past two decades, our internal medicine residency has created a unique
postgraduate education in internal medicine by incorporating a formal curriculum
in point-of-care cardiac ultrasound as a mandatory component. The details
regarding content and implementation were critical to the initial and subsequent
success of this novel program. In this paper, we discuss the evidence-based
advances, considerations, and pitfalls that we have encountered in the program's
development through the discussion of four unanticipated tasks unique to a point
of-care ultrasound curriculum. The formatted discussion of these tasks will
hopefully assist development of ultrasound programs at other institutions.
PMID- 29349309
TI - Group Learning Assessments as a Vital Consideration in the Implementation of New
Peer Learning Pedagogies in the Basic Science Curriculum of Health Profession
Programs.
AB - Inspired by reports of successful outcomes in health profession education
literature, peer learning has progressively grown to become a fundamental
characteristic of health profession curricula. Many studies, however, are
anecdotal or philosophical in nature, particularly when addressing the
effectiveness of assessments in the context of peer learning. This commentary
provides an overview of the rationale for using group assessments in the basic
sciences curriculum of health profession programs and highlights the challenges
associated with implementing group assessments in this context. The dearth of
appropriate means for measuring group process suggests that professional
collaboration competencies need to be more clearly defined. Peer learning
educators are advised to enhance their understanding of social psychological
research in order to implement best practices in the development of appropriate
group assessments for peer learning.
PMID- 29349310
TI - Integration of Dermatology-Focused Physical Diagnosis Rounds and Case-Based
Learning within the Internal Medicine Medical Student Clerkship.
AB - Background: Over half of dermatologic conditions are seen by nondermatologists,
yet medical students receive little dermatology education. Medical students in
the clinical years of training at our institution felt insecure in their physical
diagnosis skills for dermatologic conditions. Objective: The objective of this
study was to implement dermatology-focused curricula within the Internal Medicine
(IM) Core Clerkship to increase student confidence in diagnosing skin diseases.
Methods: Two dermatology-focused sessions were integrated into the IM Clerkship.
A faculty dermatologist leads students on a dermatology-focused physical
diagnosis "Skin Rounds", where patients are seen at the bedside and students
practice describing skin lesions and forming a differential diagnosis. Students
also participate in a case-based active learning session. A dermatologist selects
images of common skin conditions that students describe utilizing appropriate
terminology and offer a differential diagnosis. The impact of these sessions was
assessed through survey-based student feedback and by comparing the results from
the IM Shelf Exam before and after intervention. Results: A total of 74 students
completed the skin rounds survey (32% response rate). About 99% (n = 73) of
students felt that skin rounds were effective and useful, and 92% (n = 68) of
students reported that they felt more confident in describing skin lesions
afterward. A total of 43 students completed the case-based learning session
survey (37% response rate), and 98% (n = 42) of students strongly agreed or
agreed that the session was effective and useful. Performance on the dermatologic
questions of the IM Shelf Exam was analyzed. While not statistically significant
at P < 0.05, students improved from an average of 77% correct responses before
intervention to 79% afterward (P = 0.60). Conclusions: Our case-based and bedside
teaching interventions were met with high satisfaction from medical students and
increased their confidence in describing skin lesions. This intervention can
serve as a model to improve dermatology education and can be adapted to utilize
the IM clerkship to address curriculum inadequacies at other institutions.
PMID- 29349311
TI - Capturing the Integration of Practice-Based Learning with Beliefs, Values, and
Attitudes using Modified Concept Mapping.
AB - Practice-based learning integrates the cognitive, psychomotor, and affective
domains and is influenced by students' beliefs, values, and attitudes. Concept
mapping has been shown to effectively demonstrate students' changing concepts and
knowledge structures. This article discusses how concept mapping was modified to
capture students' perceptions of the connections between the domains of thinking
and knowing, emotions, behavior, attitudes, values, and beliefs and the specific
experiences related to these, over a period of eight months of practice-based
clinical learning. The findings demonstrate that while some limitations exist,
modified concept mapping is a manageable way to gather rich data about students'
perceptions of their clinical practice experiences. These findings also highlight
the strong integrating influence of beliefs and values on other areas of
practice, suggesting that these need to be attended to as part of a student's
educational program.
PMID- 29349312
TI - Combining Expertise: Reflecting on a Team Approach to Curriculum Development and
Implementation.
AB - Introduction: This article discussed curriculum development and implementation
using a unique collaboration of basic scientists and clinicians functioning as
course co-directors. It explores the pros, cons, and unintended consequences of
this integrated approach through reflections of the faculty involved. Methods:
Ten faculty participated in semi-structured phone interviews to reflect on their
experiences. Results: Analysis of interview transcripts revealed four key themes:
(1) the value of the basic scientist and clinician partnership, (2) strategies
for coordination, (3) balancing responsibilities, and (4) hierarchy and power.
Discussion: This study identified that both basic scientists and clinicians
experienced benefits from using a course co-director collaborative approach to
curriculum development and implementation. While challenges are also noted, the
benefits of the collaboration were evident in course organization, course
evaluation reports, student feedback, and USMLE Step I pass rate.
PMID- 29349313
TI - Prepared for Practice? Interns' Experiences of Undergraduate Clinical Skills
Training in Ireland.
AB - Background: Many previous studies on internship have reported a lack of
preparedness for the role. More recently in Ireland, medical schools have
introduced formal clinical skills training programmes. This study sought to
evaluate the impact, if any, of formal skills training in the medical training on
intern's preparedness for practice. Methods: The study utilized a survey approach
followed by focus group discussions. The aim was to identify the skills that were
taught and assessed in medical training and the skills that were actually
required in their intern year. Results: Most interns had received skills training
in designated skills laboratories. No intern had received training in all skills
advised in the European guidelines. Skills taught to all interns were intravenous
cannulation, basic life support, and basic suture. Skills required from all
interns were intravenous cannulation, phlebotomy, and arterial blood sampling.
Removal of peripherally inserted central line (PICC) lines, central lines, and
chest drains were commonly requested but not taught. Senior staff underestimated
skill abilities and expected failure. Conclusion: These findings identify
discordance between the skills taught and the skills required in the job. There
is a need for standardization in the clinical skills training to ensure that all
interns enter practice with equal competencies. Consideration should be given to
experiential learning opportunities such as subintern programmes to consolidate
learning and improve preparedness. Improvement in communications with senior
clinicians is indicated to ensure that expectations are realistic and reflective
of actual training.
PMID- 29349314
TI - How Effective is a Dental Workshop at Improving the Knowledge and Confidence of
Medical Students in the Management of Dental Emergencies?
AB - The purpose of this study was to evaluate the effect of a three-hour hands-on
workshop for medical students and residents on their pre- and postcourse
knowledge and confidence in managing dental emergencies. A 1-hour lecture
followed by four 20-minute "hands-on" skill stations on dental mannequins was
administered to a group of 30 medical students and residents. Pre- and
postworkshop questionnaire surveys were conducted. There was a significant
increase in the percent of attendees who responded correctly to three of the four
knowledge questions following the workshop (P-value < 0.005). Confidence, as
expressed in various statements, about treating dental emergencies was
significantly improved after the lecture for eight of the nine statements. These
findings indicate that dental knowledge is generally not provided during medical
training. Our interactive workshop appeared to be effective in increasing this
knowledge and self-reported confidence in handling dental emergencies. These
findings clearly indicate the need for additional dental education during medical
school. The use of a hands-on workshop may be one model for achieving this goal.
PMID- 29349315
TI - Assessing the Development of Medical Students' Personal and Professional Skills
by Portfolio.
AB - The introduction of a new domain of learning for Personal and Professional Skills
in the medical program at the University of Auckland in New Zealand has involved
the compilation of a portfolio for assessment. This departure from the
traditional assessment methods predominantly used in the past has been
challenging to design, introduce, and maintain as a relevant and authentic
assessment method. We present the portfolio format along with the process for its
introduction and appraise the challenges, strengths, and limitations of the
approach within the context of the current literature. We then outline a cyclical
model of evaluation used to monitor and fine-tune the portfolio tasks and
implementation process, in response to student and assessor feedback. The
portfolios have illustrated the level of insight, maturity, and synthesis of
personal and professional qualities that students are capable of achieving. The
Auckland medical program strives to foster these qualities in its students, and
the portfolio provides an opportunity for students to demonstrate their
reflective abilities. Moreover, the creation of a Personal and Professional
Skills domain with the portfolio as its key assessment emphasizes the importance
of reflective practice and personal and professional development and gives a
clear message that these are fundamental longitudinal elements of the program.
PMID- 29349316
TI - White Coat Ceremony as a Professional Identity Formation Activity in a United
States Family Medicine Residency Program.
AB - Introduction: White coat ceremonies (WCCs) in medical school mark the transition
of students to medicine, beginning their professional identity formation as a
physician. However, a literature/web search revealed a paucity of residency
focused WCCs. Methods: A 90-minute Family Medicine Residency (FM) WCC was
designed to support residents' professional identity formation as a specialty
physician. Through faculty narratives and brief histories of the white coat and
the specialty, the WCC concludes with new residents donning their specialty
embroidered white coats. A brief e-survey was sent to attendees, and WCC leaders
were debriefed to determine the value and key elements of WCC. Results: Seventy
nine percent of survey respondents (34/43) agreed that the WCC is an important
transition event for residents' identity while reaffirming FM values for
faculty/staff. WCC leaders identified critical steps for initiating a WCC.
Conclusion: A resident WCC formally marks the transition to specialty physician
identity. Lessons Learned: Ceremony structure will evolve over time.
PMID- 29349317
TI - Integration of Point-of-Care Ultrasound Training into Undergraduate Medical
Curricula--A Perspective from Medical Students.
AB - The utility of point of care ultrasound training during medical school is
becoming more and more evident. At the Loma Linda University School of Medicine,
we have formally integrated ultrasound education into the curriculum of all four
years. Exposure begins in the first few months of Year 1 and takes form in a
variety of educational mediums through Year 4. Whether students receive training
through mandatory sessions during physical diagnosis courses or extracurricular
workshops provided through the Ultrasound Interest Group--the experience equips
learners of at all different skill levels with the confidence to apply what they
have learned to patient care. The successful integration of ultrasound training
into the medical curriculum can be attributed to progressive administration,
devoted faculty and eager students. The perspective of medical students during
the integration process is described in this paper.
PMID- 29349318
TI - Development of a Course-Based Undergraduate Research Experience to Introduce Drug
Receptor Concepts.
AB - Course-based research experiences (CUREs) are currently of high interest due to
their potential for engaging undergraduate students in authentic research and
maintaining their interest in science, technology, engineering, and mathematics
(STEM) majors. As part of a campus-wide initiative called STEMCats, which is a
living learning program offered to freshman STEM majors at the University of
Kentucky funded by a grant from Howard Hughes Medical Institute, we have
developed a CURE for freshmen interested in pursuing health care careers. Our
course, entitled "Drug-Drug Interactions in Breast Cancer," utilized a semester
long, in-class authentic research project and instructor-led discussions to
engage students in a full spectrum of research activities, ranging from
developing hypotheses and experimental design to generating original data,
collaboratively interpreting results and presenting a poster at a campus-wide
symposium. Student's feedback indicated a positive impact on scientific
understanding and skills, enhanced teamwork and communication skills, as well as
high student engagement, motivation, and STEM belonging. STEM belonging is
defined as the extent to which a student may view the STEM fields as places where
they belong. The results obtained from this pilot study, while preliminary, will
be useful for guiding design revisions and generating appropriate objective
evaluations of future pharmacological-based CUREs.
PMID- 29349319
TI - Encouraging Subspecialty Practice by Constructively Influencing Trainees Early in
their Careers Will Improve Advocacy for Neuro-Ophthalmology among Nigerian
Ophthalmologists.
AB - This study was conducted to assess the current knowledge, attitude, and
perception of Nigerian ophthalmologists toward neuro-ophthalmology; identify
barriers to the uptake of neuro-ophthalmology as a desired subspecialty; and make
recommendations to improve interest in neuro-ophthalmology training. This was a
cross-sectional survey of ophthalmology consultants and trainees from the six
geopolitical zones of Nigeria, who were attending a national ophthalmology
conference. All consenting respondents voluntarily completed a validated self
administered questionnaire. There were 107 respondents comprising 56 males and 51
females. Majority (54.2%) of respondents were aged 40 years and younger. Almost
half (47.8%) worked at tertiary level, public health institutions. Only 10.3%
worked in private practice. Neuro-ophthalmology exposure was short and occurred
mainly during residency (65.7%), while 15% had no exposure at all. Most (80.4%)
indicated only nominal interest in neuro-ophthalmology, while only 4.6% indicated
a desire to specialize in the field. Financial constraint was the main obstacle
to the pursuit of subspecialty training. A total of 86% of respondents admitted
that full (34%) or partial (52%) Funding would motivate them to pursue the
training. Among respondents desiring part sponsorship, more than half were
willing to augment such sponsorship with personal funds. In conclusion, career
interest in neuro-ophthalmology is very low among Nigerian ophthalmologists. Late
and limited exposure to neuro-ophthalmology during medical training may be
contributing factors. Early exposure to neuro-ophthalmology during medical school
rotations, coupled with the provision of sponsored subspecialty training
opportunities, will serve to increase enrollment in the field.
PMID- 29349320
TI - Reactions to Diversity: Using Theater to Teach Medical Students about Cultural
Diversity.
AB - Training medical students to understand the effects of culture and
marginalization on health outcomes is important to the future health of
increasingly diverse populations. We devised and evaluated a short training
module on working with diversity to challenge students' thinking about the role
of both patient and practitioner culture in health outcomes. The workshop
combined didactic teaching about culture as a social determinant of health using
the cultural humility model, interactive exercises, and applied theater
techniques. We evaluated changes in the students' perceptions and attitudes over
time using the Reaction to Diversity Inventory. There was initial significant
improvement. Women and students with no past diversity training responded best.
However, scores largely reverted to baseline over 12 months.
PMID- 29349321
TI - Assessment of Clinical Reasoning by Listening to Case Presentations: VSOP Method
for Better Feedback.
AB - Case presentation is used as a teaching and learning tool in almost all clinical
education, and it is also associated with clinical reasoning ability. Despite
this, no specific assessment tool utilizing case presentations has yet been
established. SNAPPS (summarize, narrow, analyze, probe, plan, and select) and the
One-minute Preceptor are well-known educational tools for teaching how to improve
consultations. However, these tools do not include a specific rating scale to
determine the diagnostic reasoning level. Mini clinical evaluation exercise (Mini
CEX) and RIME (reporter, interpreter, manager, and educator) are comprehensive
assessment tools with appropriate reliability and validity. The vague,
structured, organized and pertinent (VSOP) model, previously proposed in Japan
and derived from RIME model, is a tool for formative assessment and teaching of
trainees through case presentations. Uses of the VSOP model in real settings are
also discussed.
PMID- 29349322
TI - Key Points to Facilitate the Adoption of Computer-Based Assessments.
AB - There are strong pedagogical arguments in favor of adopting computer-based
assessment. The risks of technical failure can be managed and are offset by
improvements in cost-effectiveness and quality assurance capability. Academic,
administrative, and technical leads at an appropriately senior level within an
institution need to be identified, so that they can act as effective advocates.
All stakeholder groups need to be represented in undertaking a detailed appraisal
of requirements and shortlisting software based on core functionality, summative
assessment life cycle needs, external compatibility, security, and usability. Any
software that is a candidate for adoption should be trialed under simulated
summative conditions, with all stakeholders having a voice in agreeing the
optimum solution. Transfer to a new system should be carefully planned and
communicated, with a programme of training established to maximize the success of
adoption.
PMID- 29349323
TI - Online Learning Tools as Supplements for Basic and Clinical Science Education.
AB - Undergraduate medical educators are increasingly incorporating online learning
tools into basic and clinical science curricula. In this paper, we explore the
diversity of online learning tools and consider the range of applications for
these tools in classroom and bedside learning. Particular advantages of these
tools are highlighted, such as delivering foundational knowledge as part of the
"flipped classroom" pedagogy and for depicting unusual physical examination
findings and advanced clinical communication skills. With accelerated use of
online learning, educators and administrators need to consider pedagogic and
practical challenges posed by integrating online learning into individual
learning activities, courses, and curricula as a whole. We discuss strategies for
faculty development and the role of school-wide resources for supporting and
using online learning. Finally, we consider the role of online learning in
interprofessional, integrated, and competency-based applications among other
contemporary trends in medical education are considered.
PMID- 29349324
TI - Engagement Patterns of High and Low Academic Performers on Facebook Anatomy
Pages.
AB - Only a few studies have investigated how students use and respond to social
networks in the educational context as opposed to social use. In this study, the
engagement of medical students on anatomy Facebook pages was evaluated in view of
their academic performance. High performers contributed to most of the
engagements. They also had a particular preference for higher levels of
engagement. Although the students were deeply involved in the educational element
of the pages, they continued to appreciate the inherent social element. The
profound engagement of the high performers indicated a consistency between
Facebook use in the educational context and better student performance. At the
same time, the deeper engagement of high performers refutes the opinion that
Facebook use is a distractor. Instead, it supports the notion that Facebook could
be a suitable platform to engage students in an educational context.
PMID- 29349325
TI - Back to the Future: What Learning Communities Offer to Medical Education.
AB - Learning communities (LCs) have increasingly been incorporated into undergraduate
medical education at a number of medical schools in the United States over the
past decade. In an Association of Medical Colleges survey of 140 medical schools,
102 schools indicated that they had LC (described as colleges or mentorship
groups; https://www.aamc.org/initiatives/cir/425510/19a.html). LCs share an
overarching principle of establishing longitudinal relationships with students
and faculty, but differ in the emphasis on specific components that may include
curriculum delivery, advising/ mentoring, student wellness, and community. The
creation of LCs requires institutional commitment to reorganize educational
processes to become more student centered. LCs are beginning to show positive
outcomes for students including benefits related to clinical skills development,
advising, and student wellness, in addition to positive outcomes for LC faculty.
PMID- 29349326
TI - Active Learning in Medical Education: Application to the Training of Surgeons.
AB - Our article defines active learning in the context of surgical education and
reviews the growing body of research on new approaches to teaching. We then
discuss future perspectives and the challenges faced by the trainee and surgeon
in applying active learning to surgical training. As modern surgical education
faces numerous challenges, we hope our article will help surgical educators in
the evaluation of curriculum development, methods of instruction, and assessment.
PMID- 29349327
TI - Faculty Development on Clinical Teaching Skills: An Effective Model for the Busy
Clinician.
AB - Introduction: The authors developed and evaluated a faculty development program
on clinical teaching skills to address barriers to participation and to impact
teaching behaviors. Methods: Four one-hour workshops were implemented over five
months. Evaluation included participant satisfaction and pre/post self
assessment. Pre/post faculty teaching ratings by trainees were compared. Results:
A total of 82% of faculty (N = 41) attended. Participants rated workshops highly
(mean, 4.43/5.00). Self-assessment of skills and comfort with teaching activities
improved. A total of 59% of residents and 40% of fellows felt that teaching
received from participating faculty was highly effective. The majority observed
targeted teaching behaviors by the faculty. Teaching ratings improved after the
workshops (P = 0.042). Conclusion: Our series of short workshops during a
standing conference time was associated with increased self-assessed skill and
comfort and an increase in faculty ratings on teaching evaluations. Effective
faculty development programs can be implemented in flexible formats and overcome
common barriers to participation.
PMID- 29349328
TI - Clinical Correlations as a Tool in Basic Science Medical Education.
AB - Clinical correlations are tools to assist students in associating basic science
concepts with a medical application or disease. There are many forms of clinical
correlations and many ways to use them in the classroom. Five types of clinical
correlations that may be embedded within basic science courses have been
identified and described. (1) Correlated examples consist of superficial clinical
information or stories accompanying basic science concepts to make the
information more interesting and relevant. (2) Interactive learning and
demonstrations provide hands-on experiences or the demonstration of a clinical
topic. (3) Specialized workshops have an application-based focus, are more
specialized than typical laboratory sessions, and range in complexity from basic
to advanced. (4) Small-group activities require groups of students, guided by
faculty, to solve simple problems that relate basic science information to
clinical topics. (5) Course-centered problem solving is a more advanced
correlation activity than the others and focuses on recognition and treatment of
clinical problems to promote clinical reasoning skills. Diverse teaching
activities are used in basic science medical education, and those that include
clinical relevance promote interest, communication, and collaboration, enhance
knowledge retention, and help develop clinical reasoning skills.
PMID- 29349329
TI - Using Learner-Centered, Simulation-Based Training to Improve Medical Students'
Procedural Skills.
AB - Purpose: To evaluate the effectiveness of a learner-centered, simulation-based
training developed to help medical students improve their procedural skills in
intubation, arterial line placement, lumbar puncture, and central line insertion.
Method: The study participants were second and third year medical students.
Anesthesiology residents provided the training and evaluated students' procedural
skills. Two residents were present at each station to train the medical students
who rotated through all 4 stations. Pre/posttraining assessment of confidence,
knowledge, and procedural skills was done using a survey, a multiple-choice test,
and procedural checklists, respectively. Results: In total, 24 students were
trained in six 4-hour sessions. Students reported feeling significantly more
confident, after training, in performing all 4 procedures on a real patient (P <
.001). Paired-samples t tests indicated statistically significant improvement in
knowledge scores for intubation, t(23) = -2.92, P < .001, and arterial line
placement, t(23) = -2.75, P < .001. Procedural performance scores for intubation
(t(23) = -17.29, P < .001), arterial line placement (t(23) = -19.75, P < .001),
lumbar puncture (t(23) = -16.27, P < .001), and central line placement (t(23) =
17.25, P < .001) showed significant improvement. Intraclass correlation
coefficients indicated high reliability in checklist scores for all procedures.
Conclusions: The simulation sessions allowed each medical student to receive
individual attention from 2 residents for each procedure. Students' written
comments indicated that this training modality was well received. Results showed
that medical students improved their self-confidence, knowledge, and skills in
the aforementioned procedures.
PMID- 29349330
TI - 'Involve Me and I Learn': Development of an Assessment Program for Research and
Critical Analysis.
AB - Evidence-based medical practice is best achieved by developing research
understanding in medical practitioners. To this end, medical councils worldwide
increasingly recognise the importance of medical schools graduating students with
well-developed research skills and research capacity. To meet this need, the
principles of programmatic assessment were implemented in designing a research
and critical analysis curriculum and assessment program that aimed to enhance the
research and critical analysis skills of medical students. The program was
developed by mapping assessment tasks to a research capabilities framework that
was in turn scaffolded to different levels of Miler's pyramid. The curriculum and
assessments were integrated with the science, clinical, and professional aspects
of the medical course. The progressive longitudinal development of research
skills, with feedback and academic mentoring, culminated in the students'
capacity to undertake an independent research project. Designing an assessment
program for learning encouraged students to develop their research capacity by
involving them in their learning.
PMID- 29349331
TI - "Thank You for Giving Me a Voice!" A Longitudinal Evaluation of Patients'
Experience of Partnering With Students in an Australian Medical School.
AB - Background: We evaluated the patient-partner experience in a longitudinal program
called Integrated Population Medicine in the Sydney Medical School to assess its
acceptability. The program exposed senior medical students to the lived
experience of chronic disease. Methods: We surveyed 267 people with chronic
conditions recruited as patient-partners by the 2012 student cohort in a mixed
methods longitudinal cohort study. Surveys were administered 'over' 18 months:
before, during, and after the program. Results: A total of 155 (58%) patient
partners completed the baseline survey; 52 patients returned all 3 surveys.
Patient-partners remained very positive about the program across all surveys.
More than 95% of respondents enjoyed interacting with the student, and most were
very positive about their role in teaching the student. Three major themes
emerged: willingness to help, a sense of gratitude and enjoyment, and a chance to
teach and learn. Participants were willing to discuss their illness experiences
and were keen to spend more time with students. Conclusions: Patients are willing
participants in longitudinal patient-partner programs. They perceive benefits for
themselves and others, for the health system, and for students and would like to
become more actively involved in medical education.
PMID- 29349332
TI - Teaching Critical Thinking in Graduate Medical Education: Lessons Learned in
Diagnostic Radiology.
AB - The 2014 Institute of Medicine report, Graduate Medical Education that Meets the
Nation's Health Needs, challenged the current graduate medical training process
and encouraged new opportunities to redefine the fundamental skills and abilities
of the physician workforce. This workforce should be skilled in critically
evaluating the current systems to improve care delivery and health. To meet these
goals, current challenges, motivations, and educational models at the medical
school and graduate medical education levels related to formal training in
nonclinical aspects of medicine, especially critical thinking, are reviewed. Our
diagnostic radiology training program is presented as a "case study" to frame the
review.
PMID- 29349334
TI - Assessing the Current Curriculum of the Nursing and Midwifery Informatics Course
at All Nursing and Midwifery Institutions in Ghana.
AB - The use of computers in the delivery of health care has significantly improved
the way health service is delivered to clients and patients in the world. Despite
the importance of computing to the delivery of health service, developing
countries have not greatly benefited from it. Nursing informatics has been in
existence and part of academic curriculum for the past 2 decades in some advanced
countries. The Ghana Nursing and Midwifery Council introduced the nursing and
midwifery informatics course during the 2015/2016 academic year. This seeks to
train student nurses on the relevance of computers to health care. Two separate
workshops were organised to ascertain the preparedness of tutors (teachers at the
nursing and midwifery training institutions) for teaching the new nursing and
midwifery informatics course as well as to compare the curriculum with other
international recommendations. The nursing and midwifery informatics course is
taught at the first year where students have not been introduced to the nursing
processes for them to appreciate the use of nursing informatics skills. It would
be better if the nursing and midwifery informatics course is rather introduced
during the second year second semester when students are about going for the
hands-on training at the various health care institutions. Examining the course
content reveals that the practical aspect within the course is very small. It is
expected that more practical contents will be introduced. Tutors are not
adequately prepared to teach this new course. More training is therefore needed
to make tutors fully prepared to teach both the theory and practical aspects of
the nursing and midwifery informatics course. It is expected that the nursing and
midwifery informatics course would prepare student nurses on all nursing
informatics competencies. It is essential that nurse educators incorporate the
entire concept of informatics into the education of nurses.
PMID- 29349333
TI - What Influences Mental Illness? Discrepancies Between Medical Education and
Conception.
AB - Objective: This preliminary study examined the differences between what was
taught during a formal medical education and medical students' and psychiatry
residents' conceptions of notions regarding the causes and determinants of mental
illness. Methods: The authors surveyed 74 medical students and 11 residents via
convenience sampling. The survey contained 18 statements which were rated twice
based on truthfulness in terms of a participant's formal education and
conception, respectively. Descriptive statistics and a Wilcoxon signed rank test
determined differences between education and conception. Results: Results showed
that students were less likely to perceive a neurotransmitter imbalance to cause
mental illness, as opposed to what was emphasized during a formal medical
education. Students and residents also understood the importance of factors such
as systemic racism and socioeconomic status in the development of mental illness,
which were factors that did not receive heavy emphasis during medical education.
Furthermore, students and residents believed that not only did mental illnesses
have nonuniform pathologies, but that the Diagnostic and Statistical Manual of
Mental Disorders also had the propensity to sometimes arbitrarily categorize
individuals with potentially negative consequences. Conclusions: If these notions
are therefore part of students' and residents' conceptions, as well as documented
in the literature, then it seems appropriate for medical education to be further
developed to emphasize these ideas.
PMID- 29349335
TI - An Innovative Clinical Skills "Boot Camp" for Dental Medicine Residents.
AB - During a 1-year hospital-based residency, dental residents are required to rotate
through many departments including surgery, medicine, and emergency medicine. It
became apparent that there was a gap between clinical skills knowledge taught in
dental school curriculum and skills required for hospital-based patient care. In
response, a simulation-based intensive clinical skill "boot camp" was created.
The boot camp provided an intensive, interactive 3-day session for the dental
residents. During the 3 days, residents were introduced to medical knowledge and
skills that were necessary for their inpatient hospital rotations but were
lacking in traditional dental school curriculum. Effectiveness of the boot camp
was assessed in terms of knowledge base and comfort through presession and
postsession surveys. According to resident feedback, this intensive introduction
for the dental residents improved their readiness for their inpatient hospital
based residency.
PMID- 29349336
TI - Interactive Journal Club: Teaching an Old Dog New Tricks.
AB - The interactive journal club incorporates basic principles of active and adult
learning in a traditional education tool to maximize opportunity to develop
critical thinking, communication skills, active reflection, and personal
confidence in these skills. Following the choice of an appropriate article, the
Designated Leader (DL) directs the discussion by presenting the title and data
from the article with instructions for their analysis but without the author's
text. The participants, except the DL, are viewing the article for the first time
and are prompted in their review of the raw data to provide their own
interpretation, discovery, and critique. Participants are challenged to become
more adept at study design, data analysis, and presentation and have indicated by
informal verbal feedback that they look forward to the interactive journal club
as it is enjoyable, relevant, and beneficial. Implementation of the interactive
journal club does not require significant training in the approach or extensive
revision or preparation of course materials.
PMID- 29349337
TI - The Relationship Between Method of Viewing Lectures, Course Ratings, and Course
Timing.
AB - Background: In recent years, medical schools have provided students access to
video recordings of course lectures, but few studies have investigated the impact
of this on ratings of courses and teachers. This study investigated whether the
method of viewing lectures was related to student ratings of the course and its
components and whether the method used changed over time. Methods: Preclinical
medical students indicated whether ratings of course lectures were based
primarily on lecture attendance, video capture, or both. Students were
categorized into Lecture, Video, or Both groups based on their responses to this
question. The data consisted of 7584 student evaluations collected over 2 years.
Results: Students who attended live lectures rated the course and its components
higher than students who only viewed the video or used both methods, although
these differences were very small. Students increasingly watched lectures
exclusively by video over time: in comparison with first-year students, second
year students were more likely to watch lectures exclusively by video; in
comparison with students in the first half of the academic year, students in the
second half of the academic year were more likely to watch lectures exclusively
by video. Conclusions: With the increase in use of lecture video recordings
across medical schools, attention must be paid to student attitudes regarding
these methods.
PMID- 29349338
TI - The Effectiveness of Computer-Assisted Instruction to Teach Physical Examination
to Students and Trainees in the Health Sciences Professions: A Systematic Review
and Meta-Analysis.
AB - Purpose: To explore knowledge and skill acquisition outcomes related to learning
physical examination (PE) through computer-assisted instruction (CAI) compared
with a face-to-face (F2F) approach. Method: A systematic literature review and
meta-analysis published between January 2001 and December 2016 was conducted.
Databases searched included Medline, Cochrane, CINAHL, ERIC, Ebsco, Scopus, and
Web of Science. Studies were synthesized by study design, intervention, and
outcomes. Statistical analyses included DerSimonian-Laird random-effects model.
Results: In total, 7 studies were included in the review, and 5 in the meta
analysis. There were no statistically significant differences for knowledge (mean
difference [MD] = 5.39, 95% confidence interval [CI]: -2.05 to 12.84) or skill
acquisition (MD = 0.35, 95% CI: -5.30 to 6.01). Conclusions: The evidence does
not suggest a strong consistent preference for either CAI or F2F instruction to
teach students/trainees PE. Further research is needed to identify conditions
which examine knowledge and skill acquisition outcomes that favor one mode of
instruction over the other.
PMID- 29349339
TI - The Impact of a Revised Curriculum on Academic Motivation, Burnout, and Quality
of Life Among Medical Students.
AB - Objective: The purpose of this study was to determine the impact of a revised
curriculum on medical student academic motivation, burnout, and quality of life.
Methods: This cross-sectional comparative study involved 2 medical school cohorts
of second year and fourth year medical students at The University of Auckland: a
cohort under a traditional curriculum (n = 437) and a cohort under a revised
curriculum (n = 446). Participants completed self-reported questionnaires
measuring academic motivation, burnout, and quality of life. Two multivariate
analyses of covariance (MANCOVAs) were conducted. Results: The response rate was
48%. No statistically significant differences were found between curriculum
cohorts for mean scores of academic motivation, personal burnout, and quality of
life. However, differences were found when comparing preclinical medical students
and students in their clinical years of training. In comparison with Year 2
medical students, the MANCOVA for Year 4 students showed a significant main
effect for the revised curriculum with respect to both physical and environmental
quality of life. Conclusions: A revised medical curriculum had a differential
effect on quality of life for Year 4 students in the latter years of medical
school who are based in a clinical learning environment.
PMID- 29349340
TI - Journeying to the White Coat Ceremony: A description of the people, situations
and experiences that inform student visions of the physician they hope to become.
AB - Little is known about the experiences that influence entering medical students'
internal concepts of themselves as future physicians. During orientation to
medical school, students were asked to write stories in response to the cue,
"Tell a story about a person or experience that inspired you to consider a career
of service in medicine." Qualitative methodology was employed to analyze 190
student stories. Thematic analysis identified descriptive details about content
and allowed comparison between the students' and School's expectations.
Inspirational settings, contexts, and individuals were identified. Nine different
inspirational events were described. Student and School expectations for the
kinds of physicians they hoped to become were generally consistent. The study
demonstrates that students do indeed bring to medical school visions of the kinds
of physicians they hope to become. Linking that vision with medical school
activities including the White Coat Ceremony provides a bridge between medical
school and students' earlier lives, thus explicitly linking orientation to
professional formation.
PMID- 29349341
TI - Why People Apply to Medical School in Iraq?
AB - Background: The motivations behind why people choose to study medicine in Iraqi
medical schools are unknown. Such information could help school pupils to make
more informed career decisions and assist medical schools in enhancing the
student selection process. Aims: To investigate why people choose to study
medicine in Iraq. Subjects and methods: The first-year students admitted on the
academic year 2015-2016 to Baghdad College of Medicine, University of Baghdad,
were invited to complete a structured questionnaire, which was administered
through the college electronic education portal. The data were analyzed using IBM
SPSS version 21 software. Results: A total of 152 (50% response rate) students
responded. Women constituted 69.1% of respondents. Most students (61.8%) had made
their choice by themselves without family pressure. The most frequent reasons
that affected this choice were "humanitarian reasons and a wish to provide help
to others" as well as "childhood dream," "positive community appraisal of
doctors," and "ready availability of work for physicians." About three-quarters
(73.6%) of the students made some inquiry about medical school before making
their choice, and the people asked were most frequently a medical student or a
doctor. Information provided by the consulted parties was regarded as
satisfactory by 64.2% of the surveyed students, had a positive value in 47.2%,
and affected their decision in 34.9%. The highest proportion (42.2%) of the study
sample was thinking about studying medicine since primary school. In addition,
students with personal preference made their choice at a significantly younger
age. Conclusions: Reasons to apply for medical schools in Iraq are similar to
those in many countries. Most of the students who inquired about studying
medicine had not contacted the medical school itself.
PMID- 29349342
TI - No Ifs, Ands, or Buts: Leveraging Population Health to Focus on the Care of
Patients Who Smoke.
AB - We developed a multidisciplinary curriculum to improve our residents' proficiency
with smoking cessation counseling and prescribing of nicotine replacement therapy
(NRT). The curriculum included a didactic portion, informational handouts, and a
panel management component during which residents did telephone outreach and
clinic in-reach to address high rates of smoking among patients. Residents rated
their confidence with smoking cessation counseling and clinical knowledge before
and after the intervention. We also tracked the number of patients flagged in the
electronic medical record as smokers, the number of patients contacted, and the
number of patients who received counseling. Although we did not make
statistically significant improvements in perceived confidence with prescribing
NRT, we found that there is an urgent need to address smoking cessation in the
primary care setting and that working with a clinical pharmacist and psychologist
offered a comprehensive approach. Furthermore, by anchoring the intervention with
a population health component, almost 200 patients benefited from outreach
efforts.
PMID- 29349343
TI - Increasing Medical Trainees' Empathy Through Volunteerism and Mentorship.
AB - Background: Within medical education, there have been recent calls for increased
understanding and exposure to poverty to increase trainees' empathy toward the
underserved. Students participating in Michigan Cardiovascular Outcomes Research
and Reporting Program research program volunteered at World Medical Relief (WMR)
in Detroit, Michigan, a nonprofit organization which recycles medical equipment
for developing countries and within greater Detroit. Participants' perceptions of
the underserved were measured before and after the experience. Methods:
Preliminary questionnaires were given to participants prior to and after
exposures at WMR. Questionnaires examined participants' attitudes toward the
underserved, knowledge of medical supply reuse, and their perceived ability to
impact change. P values of <.025 were considered significant. Results: A total of
39 participants completed the survey, 77% previously volunteered, 33% had
volunteered internationally. Participants were >4* more likely than previously to
have knowledge of the variety of recycled medical supplies at WMR. Prior to
volunteering, 48.7% of participants gave little thought to how excess medical
supplies could be collected versus 0% after exposure. Participants were 1.5* more
likely to agree that the experience was enhanced working with their peers and
2.7* more likely to consider starting their own organization/intervention for
medical supply donations. Those participants that never previously volunteered
were 1.3* more likely to do so with encouragement from a mentor. Conclusions:
Encouraging exposure to such service programs resulted in enhanced knowledge of
community resources and increased motivation to participate in outreach and
belief of individual responsibility to care for the underserved. Incorporating
volunteerism into traditional education programs offers the opportunity to build
awareness and interest in students reaching out to the underserved.
PMID- 29349344
TI - Adaptation and Evaluation of Military Resilience Skills Training for Pediatric
Residents.
AB - Background: An evidence-based trauma-informed resilience skills training program
developed for deployed military personnel was adapted and pilot-tested with
pediatric residents. We anticipated high satisfaction ratings and changes in
knowledge, beliefs, and self-efficacy related to coping with stress and trauma.
Methods: The intervention included 6 skill-based modules covering emotion
regulation, communication with angry patients and parents, reflective narrative,
inspirational goal setting, problem-solving, and developing a self-care toolbox.
An optional survey was administered before and after the training. Results: After
training, 76% rated resilience skills as important, 60% were satisfied, and 82%
indicated the training changed how they will respond to patient-related grief and
trauma. They became more likely to believe attendings are affected by patient
deaths and to know what helps them cope when they disagree with the medical
decision making of others, more skilled in recognizing signs of stress and
trauma, and more knowledgeable about evidence-based interventions.
PMID- 29349345
TI - Medical Student Perceptions of Learner-Initiated Feedback Using a Mobile Web
Application.
AB - Feedback, especially timely, specific, and actionable feedback, frequently does
not occur. Efforts to better understand methods to improve the effectiveness of
feedback are an important area of educational research. This study represents
preliminary work as part of a plan to investigate the perceptions of a student
driven system to request feedback from faculty using a mobile device and Web
based application. We hypothesize that medical students will perceive learner
initiated, timely feedback to be an essential component of clinical education.
Furthermore, we predict that students will recognize the use of a mobile device
and Web application to be an advantageous and effective method when requesting
feedback from supervising physicians. Focus group data from 18 students enrolled
in a 4-week anesthesia clerkship revealed the following themes: (1) students
often have to solicit feedback, (2) timely feedback is perceived as being
advantageous, (3) feedback from faculty is perceived to be more effective, (4)
requesting feedback from faculty physicians poses challenges, (5) the decision to
request feedback may be influenced by the student's clinical performance, and (6)
using a mobile device and Web application may not guarantee timely feedback.
Students perceived using a mobile Web-based application to initiate feedback from
supervising physicians to be a valuable method of assessment. However, challenges
and barriers were identified.
PMID- 29349346
TI - Characteristics of electroencephalogram signatures in sedated patients induced by
various anesthetic agents.
AB - Devices that monitor the depth of hypnosis based on the electroencephalogram
(EEG) have long been commercialized, and clinicians use these to titrate the
dosage of hypnotic agents. However, these have not yet been accepted as standard
monitoring devices for anesthesiology. The primary reason is that the use of
these monitoring devices does not completely prevent awareness during surgery,
and the development of these devices has not taken into account the
neurophysiological mechanisms of hypnotic agents, thus making it possible to show
different levels of unconsciousness in the same brain status. An alternative is
to monitor EEGs that are not signal processed with numerical values presented by
these monitoring devices. Several studies have reported that power spectral
analysis alone can distinguish the effects of different hypnotic agents on
consciousness changes. This paper introduces the basic concept of power spectral
analysis and introduces the EEG characteristics of various hypnotic agents that
are used in sedation.
PMID- 29349347
TI - Pain measurement in oral and maxillofacial surgery.
AB - Regardless of whether it is acute or chronic, the assessment of pain should be
simple and practical. Since the intensity of pain is thought to be one of the
primary factors that determine its effect on a human's overall function and
sense, there are many scales to assess pain. The aim of the current article was
to review pain intensity scales that are commonly used in dental and oral and
maxillofacial surgery (OMFS). Previous studies demonstrated that multidimensional
scales, such as the McGill Pain Questionnaire, Short form of the McGill Pain
Questionnaire, and Wisconsin Brief Pain Questionnaire were suitable for assessing
chronic pain, while unidimensional scales, like the Visual Analogue Scales (VAS),
Verbal descriptor scale, Verbal rating scale, Numerical rating Scale, Faces Pain
Scale, Wong-Baker Faces Pain Rating Scale (WBS), and Full Cup Test, were used to
evaluate acute pain. The WBS is widely used to assess pain in children and
elderly because other scales are often difficult to understand, which could
consequently lead to an overestimation of the pain intensity. In dental or OMFS
research, the use of the VAS is more common because it is more reliable, valid,
sensitive, and appropriate. However, some researchers use NRS to evaluate OMFS
pain in adults because this scale is easier to use than VAS and yields relatively
similar pain scores. This review only assessed pain scales used for post
operative OMFS or dental pain.
PMID- 29349348
TI - The effect of tulobuterol patches on the respiratory system after endotracheal
intubation.
AB - Background: Endotracheal intubation during anesthesia induction may increase
airway resistance (Raw) and decrease dynamic lung compliance (Cdyn). We
hypothesized that prophylactic treatment with a transdermal beta2-agonist
tulobuterol patch (TP) would help to reduce the risk of bronchospasm after
placement of the endotracheal tube. Methods: Eighty-two American Society of
Anesthesiologists (ASA) category I or II adult patients showing obstructive
patterns were divided randomly into a control and a TP group (n = 41 each). The
night before surgery, a 2-mg TP was applied to patients in the TP group. Standard
monitors were recorded, and target controlled infusion (TCI) with propofol and
remifentanil was used for anesthesia induction and maintenance. Simultaneously,
end-tidal carbon dioxide, Raw, and Cdyn were determined at 5, 10, and 15 min
intervals after endotracheal intubation. Results: There was no significant
difference in demographic data between the two groups. The TP group was
associated with a lower Raw and a higher Cdyn, as compared to the control group.
Raw was significantly lower at 10 min (P < 0.05) and 15 min (P < 0.01), and Cdyn
was significantly higher at 5 min (P < 0.05) and 15 min (P < 0.01) in the TP
group. A trend towards a lower Raw was observed showing a statistically
significant difference 5 min after endotracheal intubation (P < 0.01) in each
group. Conclusions: Prophylactic treatment with TP showed a bronchodilatory
effect through suppressing an increase in Raw and a decrease in Cdyn after
anesthesia induction without severe adverse effects.
PMID- 29349349
TI - A retrospective analysis of outpatient anesthesia management for dental treatment
of patients with severe Alzheimer's disease.
AB - Background: The number of patients with Alzheimer's disease is growing worldwide,
and the proportion of patients requiring dental treatment under general
anesthesia increases with increasing severity of the disease. However, outpatient
anesthesia management for these patients involves great risks, as most patients
with Alzheimer's disease are old and may show reduced cardiopulmonary functions
and have cognitive disorders. Methods: This study retrospectively investigated 43
patients with Alzheimer's disease who received outpatient anesthesia for dental
treatment between 2012-2017. Pre-anesthesia patient evaluation, dental treatment
details, anesthetics dose, blood pressure, duration and procedure of anesthesia,
and post-recovery management were analyzed and compared between patients who
underwent general anesthesia or intravenous sedation. Results: Mean age of
patients was about 70 years; mean duration of Alzheimer's disease since diagnosis
was 6.3 years. Severity was assessed using the global deterioration scale; 62.8%
of patients were in level >= 6. Mean duration of anesthesia was 178 minutes for
general anesthesia and 85 minutes for intravenous sedation. Mean recovery time
was 65 minutes. Eleven patients underwent intravenous sedation using propofol,
and 22/32 cases involved total intravenous anesthesia using propofol and
remifentanil. Anesthesia was maintained with desflurane for other patients. While
maintaining anesthesia, inotropic and atropine were used for eight and four
patients, respectively. No patient developed postoperative delirium. All patients
were discharged without complications. Conclusion: With appropriate anesthetic
management, outpatient anesthesia was successfully performed without
complications for dental treatment for patients with severe Alzheimer's disease.
PMID- 29349350
TI - A comparison of the effects of epinephrine and xylometazoline in decreasing nasal
bleeding during nasotracheal intubation.
AB - Background: Various techniques have been introduced to decrease complications
during nasotracheal intubation. A common practice is to use nasal packing with a
cotton stick and 0.01% epinephrine jelly. However, this procedure can be painful
to patients and can damage the nasal mucosa. Xylometazoline spray can induce
effective vasoconstriction of the nasal mucosa without direct nasal trauma. In
this study, we aimed to compare the efficacy of these two methods. Methods:
Patients were randomly allocated into two groups (n = 40 each): xylometazoline
spray group or epinephrine packing group. After the induction of general
anesthesia, patients allocated to the xylometazoline spray group were treated
with xylometazoline spray to induce nasal cavity mucosa vasoconstriction, and the
epinephrine packing group was treated with nasal packing with two cotton sticks
and 0.01% epinephrine jelly. The number of attempts to insert the endotracheal
tube into the nasopharynx, the degree of difficulty during insertion, and
bleeding during bronchoscopy were recorded. An anesthesiologist, blinded to the
intubation method, estimated the severity of epistaxis 5 min after intubation and
postoperative complications. Results: No significant intergroup difference was
observed in navigability (P = 0.465). The xylometazoline spray group showed
significantly less epistaxis during intubation (P = 0.02). However, no
differences were observed in epistaxis 5 min after intubation or postoperative
epistaxis (P = 0.201). No inter-group differences were observed in complications
related to nasal intubation and nasal pain. Conclusion: Xylometazoline spray is a
good alternative to nasal packing for nasal preparation before nasotracheal
intubation.
PMID- 29349351
TI - The relationship between subjective oral health and dental fear in Korean
adolescents.
AB - Background: This study is aimed to evaluate the level of fear and to reduce the
overall fear, thereby enabling patients to receive treatment via timely visits.
Methods: In a survey conducted by 460 South Korean middle school students, we
used 453 data that faithfully responded to the survey. Multiple regression
analysis was conducted to investigate the factors influencing subjective oral
health and dental fear. The significance level used for statistical significance
was alpha = 0.05. Results: The level of fear was higher for upper grade, female
students. The factors affecting dental fear were higher for gingival bleeding and
dental pain. Regarding factors for dental fear affecting subjective oral health,
lower fear of puncture needle and tooth removal tool resulted in higher
subjective oral health. Conclusion: The study found that adolescents had higher
fear of dental care when they had gingival bleeding and tooth pain. Gingival
bleeding is a symptom of early gingival disease and dental pain is likely due to
advanced dental caries. These results suggested that it is necessary to have a
program to reduce dental fear and anxiety as well as a program to prevent dental
diseases through regular periodic screening and education.
PMID- 29349352
TI - Learning fiberoptic intubation for awake nasotracheal intubation.
AB - Background: Fiberoptic nasotracheal intubation (FNI) is performed if it is
difficult to open the mouth or if intubation using laryngoscope is expected to be
difficult. However, training is necessary because intubation performed by
inexperienced operators leads to complications. Methods: Every resident performed
intubation in 40 patients. Success of FNI was evaluated as the time of FNI. First
intubation time was restricted to 2 min 30 s. If the second attempt was
unsuccessful, it was considered a failed case, and a specialist performed
nasotracheal intubation. If the general method of intubation was expected to be
difficult, awake intubation was performed. The degree of nasal bleeding during
intubation was also evaluated. Results: The mean age of the operators (11 men, 7
women) was 27.8 years. FNI was performed in a total of 716 patients. The success
rate was 88.3% for the first attempt and 94.6% for the second attempt. The
failure rate of intubation in anesthetized patients was 4.9%, and 13.6% in awake
patients. When intubation was performed in anesthetized patients, the failure
rate from the first to fifth trial was 9.6%, which decreased to 0.7% when the
number of trials increased to > 30 times. In terms of awake intubation, there was
no failed attempt when the resident had performed the FNI > 30 times. The number
of FNIs performed and nasal bleeding were important factors influencing the
failure rate. Conclusion: The success rate of FNI increased as the number of FNI
performed by residents increased despite the nasal bleeding.
PMID- 29349353
TI - Estimation of optimal nasotracheal tube depth in adult patients.
AB - Background: The aim of this study was to estimate the optimal depth of
nasotracheal tube placement. Methods: We enrolled 110 patients scheduled to
undergo oral and maxillofacial surgery, requiring nasotracheal intubation. After
intubation, the depth of tube insertion was measured. The neck circumference and
distances from nares to tragus, tragus to angle of the mandible, and angle of the
mandible to sternal notch were measured. To estimate optimal tube depth,
correlation and regression analyses were performed using clinical and
anthropometric parameters. Results: The mean tube depth was 28.9 +/- 1.3 cm in
men (n = 62), and 26.6 +/- 1.5 cm in women (n = 48). Tube depth significantly
correlated with height (r = 0.735, P < 0.001). Distances from nares to tragus,
tragus to angle of the mandible, and angle of the mandible to sternal notch
correlated with depth of the endotracheal tube (r = 0.363, r = 0.362, and r =
0.546, P < 0.05). The tube depth also correlated with the sum of these distances
(r = 0.646, P < 0.001). We devised the following formula for estimating tube
depth: 19.856 + 0.267 * sum of the three distances (R2 = 0.432, P < 0.001).
Conclusion: The optimal tube depth for nasotracheally intubated adult patients
correlated with height and sum of the distances from nares to tragus, tragus to
angle of the mandible, and angle of the mandible to sternal notch. The proposed
equation would be a useful guide to determine optimal nasotracheal tube
placement.
PMID- 29349354
TI - Awake intubation in a patient with huge orocutaneous fistula: a case report.
AB - Mask ventilation, the first step in airway management, is a rescue technique when
endotracheal intubation fails. Therefore, ordinary airway management for the
induction of general anesthesia cannot be conducted in the situation of difficult
mask ventilation (DMV). Here, we report a case of awake intubation in a patient
with a huge orocutaneous fistula. A 58-year-old woman was scheduled to undergo a
wide excision, reconstruction with a reconstruction plate, and supraomohyoid neck
dissection on the left side and an anterolateral thigh flap due to a huge
orocutaneous fistula that occurred after a previous mandibulectomy and flap
surgery. During induction, DMV was predicted, and we planned an awake intubation.
The patient was sedated with dexmedetomidine and remifentanil. She was intubated
with a nasotracheal tube using a video laryngoscope, and spontaneous ventilation
was maintained. This case demonstrates that awake intubation using a video
laryngoscope can be as good as a fiberoptic scope.
PMID- 29349355
TI - Facial blanching after inferior alveolar nerve block anesthesia: an unusual
complication.
AB - The present case report describes a complication involving facial blanching
symptoms occurring during inferior alveolar nerve block anesthesia (IANBA).
Facial blanching after IANBA can be caused by the injection of an anesthetic into
the maxillary artery area, affecting the infraorbital artery.
PMID- 29349356
TI - QT-interval prolongation due to medication found in the preoperative evaluation.
AB - QT prolongation is an electrocardiographic change that can lead to lethal
arrhythmia. Acquired QT prolongation is known to be caused by drugs and
electrolyte abnormalities. We report three cases in which the prolonged QT
interval was improved at the time of operation by briefly discontinuing the drugs
suspected to have caused the QT prolongation observed on preoperative
electrocardiography. The QTc of cases 1, 2, and 3 improved from 518 to 429 ms,
463 to 441 ms, and 473 to 443 ms on discontinuing the use of a gastrointestinal
prokinetic agent, a proton pump inhibitor, and a molecular targeted drug,
respectively. These cases were considered to have drug-induced QT prolongation.
We reaffirmed that even drugs administered for conditions unrelated to cardiac
diseases can have adverse side effect of QT prolongation. In conclusion, our
cases indicate that dental surgeons should be aware of the dangerous and even
potentially lethal side effects of QT prolongation. For safe oral and
maxillofacial surgery, cooperation with medical departments in various fields is
important.
PMID- 29349358
TI - 95gTc and 96gTc as alternatives to medical radioisotope 99mTc.
AB - We studied 95gTc and 96gTc as alternatives to the medical radioisotope 99mTc.
96gTc (95gTc) can be produced by (p, n) reactions on an enriched 96Mo (95Mo)
target with a proton beam provided by a compact accelerator such as a medical
cyclotron that generate radioisotopes for positron emission tomography (PET). The
gamma-rays are measured with an electron-tracking Compton camera (ETCC). We
calculated the relative intensities of the gamma-rays from 95gTc and 96gTc. The
calculated gamma-ray intensity of a 96gTc (95gTc) nucleus is as high as 63% (70%)
of that of a 99mTc nucleus. We also calculated the patient radiation doses of
95gTc and 96gTc, which were larger than that of 99mTc by a factor of 2-3 based on
the applied assumptions. A medical PET cyclotron which can provide proton beams
with energies of 11-12 MeV and a current of 100 MUA can produce 12 GBq (39 GBq)
of 96gTc (95gTc) for operation time of 8 h, which can be used for 240 (200)
diagnostic scans.
PMID- 29349359
TI - Resensitization of methicillin-resistant Staphylococcus aureus by amoxapine, an
FDA-approved antidepressant.
AB - The rapid increase in bacterial resistance to antibiotics is a global healthcare
crisis. Non-antibiotic pharmaceuticals that have attained approval by the United
States Food and Drug Administration have the potential to be repurposed as
bacterial resistance-modifying agents and therefore could become valuable
resources in our battle against antibiotic-resistant microbes. Amoxapine is a
tetracyclic antidepressant used in the treatment of major depressive disorder.
Here we demonstrate the ability of amoxapine to resensitize methicillin-resistant
Staphylococcus aureus strain ATCC 43300 to oxacillin in both agar diffusion and
broth microdilution assays. Amoxapine also reduced the bacterial cleavage of
nitrocefin in a dose-dependent manner, suggesting that it may exert its adjuvant
effects through reduction of beta-lactamase activity.
PMID- 29349357
TI - Comprehensive cytotoxicity studies of superparamagnetic iron oxide nanoparticles.
AB - Recently lots of efforts have been taken to develop superparamagnetic iron oxide
nanoparticles (SPIONs) for biomedical applications. So it is utmost necessary to
have in depth knowledge of the toxicity occurred by this material. This article
is designed in such way that it covers all the associated toxicity issues of
SPIONs. It mainly emphasis on toxicity occurred at different levels including
cellular alterations in the form of damage to nucleic acids due to oxidative
stress and altered cellular response. In addition focus is been devoted for in
vitro and in vivo toxicity of SPIONs, so that a better therapeutics can be
designed. At the end the time dependent nature of toxicity and its ultimate faith
inside the body is being discussed.
PMID- 29349361
TI - Endovascular repair of an innominate artery pseudoaneurysm using the Valiant Mona
LSA branched graft device.
AB - A 60-year-old woman involved in a motor vehicle collision presented with a
traumatic pseudoaneurysm of the innominate artery origin in addition to multiple
concomitant injuries. She was classified as a high-risk candidate for open
repair. An experimental thoracic branched graft device was used for coverage of
the injury with the addition of a right carotid-to-left carotid-to-left
subclavian artery bypass. Follow-up imaging showed resolution of the
pseudoaneurysm and patency of her bypass grafts. This is the first described use
of the Mona LSA Branch Thoracic Stent Graft System (Medtronic, Minneapolis, Minn)
in the innominate artery.
PMID- 29349360
TI - ULTRASOUND INDUCED MICROBUBBLE CAVITATION FOR THE TREATMENT OF CATHETERIZATION
INDUCED VASOSPASM.
PMID- 29349362
TI - Bridging stent repair of type III endoleak causing aortocaval fistula after
branched aortic endovascular repair.
AB - A 62-year-old man presented to our department with abdominal pain and diarrhea
for 3 weeks on a background of previous branched endovascular repair for a
thoracoabdominal aneurysm. A triple-phase computed tomography scan of his abdomen
and pelvis showed a large aortocaval fistula caused by a type III endoleak from a
dislodged superior mesenteric artery stent. He was successfully treated with a
BeGraft (Bentley Innomed, Hechingen, Germany) by using an endovascular technique.
PMID- 29349363
TI - A novel technique combining laparoscopic and endovascular approaches using image
fusion guidance for anterior embolization of type II endoleak.
AB - Type II endoleak (T2E) leading to aneurysm sac enlargement is one of the
challenging complications associated with endovascular aneurysm repair. Recent
guidelines recommend embolization of T2E associated with aneurysmal sac
enlargement. Various percutaneous and endovascular techniques have been reported
for embolization of T2E. We report a novel technique for T2E embolization
combining laparoscopic and endovascular approaches using preoperative image
fusion. We believe our technique provides a more direct access to the lumbar
feeding vessels that is typically challenging with transarterial or translumbar
embolization techniques.
PMID- 29349364
TI - Endovascular repair of a thoracic aortic transection 31 years after blunt trauma.
PMID- 29349365
TI - Debridement of atheroma in the proximal clamp site under hypothermic circulatory
arrest for repair of abdominal aortic aneurysm with severe atherosclerosis.
AB - Postoperative renal and other ischemic complications due to atheroembolization
after clamping of the proximal site of an abdominal aortic aneurysm are
catastrophic. We present here a method of debridement of atheroma and clamping
under hypothermic circulatory arrest to avoid iatrogenic atheroembolization.
PMID- 29349366
TI - An 18-cm unruptured abdominal aortic aneurysm.
AB - Abdominal aortic aneurysm (AAA) is a significant source of morbidity and ranked
by the Centers for Disease Control and Prevention as the 15th leading cause of
death among adults aged 60 to 64 years. Size confers the largest risk factor for
aneurysm rupture, with aneurysms >6 cm having an annual rupture risk of 14.1%. We
present the case of a 60-year-old man found on ultrasound imaging at a health
fair screening to have a 15-cm AAA. Follow-up computed tomography angiography
revealed an 18-cm * 10-cm unruptured, infrarenal, fusiform AAA. Giant AAAs,
defined as >11 cm, are rarely described in the literature. Our patient underwent
successful transperitoneal AAA repair with inferior mesenteric artery
reimplantation and was discharged home on operative day 6. We believe this case
represents one of the largest unruptured AAAs in the literature and demonstrates
the feasible approach for successful repair.
PMID- 29349367
TI - A rare anatomic variant of a single-conduit supraclavicular cephalic arch
draining into the external jugular vein presenting with recurrent arteriovenous
fistula stenosis in a hemodialysis patient.
AB - The cephalic arch is a common location of stenosis, especially in brachiocephalic
fistulas. The cephalic arch has a number of anatomic variations. Cephalic arch
stenoses are often resistant and have poor primary patency. Here we describe an
unusual case of a hemodialysis patient with a single-conduit supraclavicular
cephalic arch draining into the external jugular vein presenting with recurrent
cephalic arch stenoses and external jugular vein stenosis. In our view, extrinsic
compression by the clavicle may contribute to the high rate of recurrence, the
lack of complete dilation of even high-pressure balloons, and a theoretically
heightened risk of rupture when cutting balloons are used.
PMID- 29349368
TI - Severe generalized dermatitis in a nickel-allergic patient with a popliteal
artery nitinol stent.
AB - We present the case of a patient who developed a full-body desquamating macular
papular, pruritic rash after endovascular placement of a popliteal artery nitinol
stent for acute limb ischemia. The rash was resistant to high-dose steroid and
immunosuppressive treatment and intensive topical treatment. Patch testing
revealed nickel allergy. The stented arterial segment was removed, with
significant improvement in his symptoms that allowed the cessation of prednisone
and topical treatments. The epidemiology, pathophysiology, and clinical effect of
nickel allergy are discussed in addition to the use of nickel-alloy stents.
PMID- 29349369
TI - Potentially stress-induced acute splanchnic segmental arterial mediolysis with a
favorable spontaneous outcome.
AB - A 62-year-old woman presented with hemithoracic anesthesia and acute abdominal
pain following a violent psychological stress. Magnetic resonance imaging showed
a thoracic hematoma with arachnoiditis of the spinal cord. Tomography revealed a
typical aspect of segmental arterial mediolysis with multiple aneurysms and
stenoses of the splanchnic arteries, confirmed by abdominal arteriography. There
was no argument for hereditary, traumatic, atherosclerotic, infectious, or
inflammatory arterial disease. Segmental arterial mediolysis was diagnosed on the
basis of the radiologic data and probably involved both medullary and splanchnic
arteries. The patient spontaneously recovered and was in good health 18 months
later.
PMID- 29349370
TI - Endovascular treatment with flow-diverting stents of symptomatic superior
mesenteric artery after dissection aneurysm.
AB - Isolated and spontaneous superior mesenteric artery dissection is a rare cause of
acute abdominal pain. Whereas there is widespread consensus on conservative
treatment of asymptomatic forms, revascularization would seem indicated in
symptomatic complicated cases. A 73-year-old man presented with worsening
epigastric pain. A computed tomography scan revealed an isolated and spontaneous
superior mesenteric artery dissection with aneurysmal evolution of the false
lumen, involving multiple side branches. The postdissection aneurysm was treated
by endovascular exclusion with flow-diverting stents. The abdominal pain was
completely relieved, and the patient remained asymptomatic at follow-up.
PMID- 29349371
TI - External ventricular drain as a nontraumatic suction device in carotid
endarterectomy.
AB - Carotid endarterectomy is a commonly performed operation to remove plaque at the
region of the carotid bifurcation. We present our technique to keep the field
clear and to minimize potential trauma to the carotid using a neurosurgical
external ventricular drain passed behind the common carotid and placed in the
dependent position under the arteriotomy.
PMID- 29349372
TI - Successful off-label use of the GORE EXCLUDER Iliac Branch Endoprosthesis to
preserve gluteal perfusion during staged endovascular repair of bilateral
isolated hypogastric aneurysms.
AB - Endovascular repair of iliac artery aneurysms has emerged as an alternative to
traditional open surgical repair. Although there is little consensus on
indications to preserve hypogastric blood flow during aneurysm repair, it is well
understood that complications from bilateral hypogastric occlusion may be
significant. The GORE EXCLUDER Iliac Branch Endoprosthesis (W. L. Gore and
Associates, Flagstaff, Ariz) received United States Food and Drug Administration
approval in March 2016 for treatment of common iliac artery and aortoiliac
aneurysms. This case report discusses an off-label use of GORE EXCLUDER Iliac
Branch Endoprosthesis to maintain pelvic perfusion during treatment of bilateral
internal iliac artery aneurysms without surrounding aortoiliac pathology.
PMID- 29349373
TI - Lower extremity compartment syndrome after elective percutaneous fenestrated
endovascular repair of an abdominal aortic aneurysm.
AB - Ischemic complications after fenestrated endovascular aortic aneurysm repair
(FEVAR) can result in significant morbidity and mortality. We present a case of a
65-year-old man who underwent a FEVAR complicated by bilateral lower extremity
compartment syndrome requiring four-compartment fasciotomies. This ischemic
complication was likely caused by sheath occlusion because the patient had no
evidence of arterial injury or distal plaque embolization. This case highlights
the importance of careful postoperative monitoring after FEVAR, because the
larger sheaths required can be occlusive and result in lower extremity ischemia,
even for relatively short cases.
PMID- 29349374
TI - Utilization of arterial grafts in foot replantation.
AB - Our subject is a 36-year-old man who presented to the emergency department with
bilateral lower extremity amputation at the level of the distal third of the
tibia after a car accident. Surgery was planned for below-knee amputation of the
right lower extremity and replantation of the left foot. The arteries dissected
from the iatrogenically amputated segment were used as grafts to repair vascular
gaps during the replantation. The patient's follow-up had been problem free. We
concluded that whenever possible, amputated parts unsuitable for replantation
should be examined thoroughly and neurovascular structures that might be used as
grafts should be preserved.
PMID- 29349375
TI - The use of bovine pericardial patch for vascular reconstruction in infected
fields for transplant recipients.
AB - Infectious vascular complications affecting transplant recipients may lead to
severe morbidity and graft loss. This is a retrospective review of vascular
repair with bovine pericardial patch (BPP) in infected fields for
immunosuppressed patients. BPP was used as either a patch or an interposition
graft. Five cases of arterial reconstruction in infected fields using BPP were
performed. There were no complications related to bleeding, thrombosis, or
recurrent infection. In our limited experience, the use of BPP as a vascular
patch is successful, and it represents an alternative when vascular
reconstruction is needed in the context of infected fields.
PMID- 29349376
TI - Directional tip control technique for optimal stent graft alignment in angulated
proximal aortic landing zones.
AB - Angulated anatomy in the aorta, such as tortuous infrarenal aortic necks or steep
aortic arches, is a significant challenge for endovascular aortic repair because
it often causes inadequate sealing and fixation, which may lead to treatment
failure. We have developed a technique using off-the-shelf equipment to precisely
control the deployment of stent grafts in challenging landing zones. The key of
this technique is to create a through-and-through wire between two access sites
and to use a guiding device over the wire. This technique is best used with stent
grafts without nose cones. We present an endovascular aneurysm repair case and a
thoracic endovascular aortic repair case with challenging proximal landing zones
treated by this technique. In both cases, technical success was attained, and
follow-up imaging demonstrated well-aligned stent grafts. Our directional tip
control technique is easy and effective. It can be a good technical solution for
endovascular aortic treatment in angulated anatomy.
PMID- 29349377
TI - Emergency thoracic endovascular aortic repair with celiac artery coverage in
hereditary hemorrhagic telangiectasia.
AB - Celiac artery (CA) coverage during thoracic endovascular aortic repair has been
demonstrated to be a feasible and effective strategy for selected cases. However,
there is a potential risk of ischemic complications due to CA coverage in
patients with certain types of hereditary hemorrhagic telangiectasia (HHT).
Herein, we report a case of thoracoabdominal aortic rupture in a patient with HHT
that was successfully treated with emergency thoracic endovascular aortic repair
covering the CA preceded by hepatic artery bypass. We also review the hepatic
circulatory derangements and unique considerations in the surgical management of
HHT.
PMID- 29349378
TI - Hand-arm vibration syndrome: A rarely seen diagnosis.
AB - Hand-arm vibration syndrome (HAVS) is a collection of sensory, vascular, and
musculoskeletal symptoms caused by repetitive trauma from vibration. This case
report demonstrates how to diagnose HAVS on the basis of history, physical
examination, and vascular imaging and its treatment options. A 41-year-old man
who regularly used vibrating tools presented with nonhealing wounds on his right
thumb and third digit. Arteriography revealed occlusions of multiple arteries in
his hand with formation of collaterals. We diagnosed HAVS, and his wounds healed
after several weeks with appropriate treatment. HAVS is a debilitating condition
with often irreversible vascular damage, requiring early diagnosis and treatment.
PMID- 29349379
TI - Common femoral vein stent placement in a frozen abdomen causing acute limb
ischemia.
AB - A 73-year-old woman was admitted for left groin bleeding through an open wound
near a fungating left inguinal mass from advanced anal carcinoma. The
interventional radiology service placed left iliac vein and common femoral vein
stents as there was concern for communication and involvement of the left common
femoral vein with the open wound, contributing to groin hemorrhage. After the
procedure, the patient developed limb ischemia related to mass effect of the
stent on the left common femoral vein stent artery. She was revascularized by
placement of a left common femoral vein stent artery stent. This report describes
a viable option for revascularization in the rare occurrence of limb ischemia
related to venous stenting.
PMID- 29349380
TI - Type IV popliteal arterial entrapment associated with an osteochondroma.
AB - Popliteal artery entrapment syndrome is a rare cause of peripheral vascular
disease, often affecting young adults. Multiple studies have shown that
osteochondromas can cause vascular injury. Intermittent compression,
pseudoaneurysm, thrombosis, distal embolism, and venous thrombosis have all been
described as possible complications. Here we present a case of popliteal arterial
entrapment type IV with an associated tibial osteochondroma.
PMID- 29349381
TI - Acute infection of Viabahn stent graft in the popliteal artery.
AB - Peripheral stents are increasingly used for treatment of peripheral arterial
disease, yet all implanted devices are potentially at risk for infection. We
describe a 51-year-old man who underwent stenting in the femoropopliteal artery
and presented 3 days later with leg pain, fever, and evidence of peripheral
stigmata of embolization. Blood cultures grew methicillin-resistant
Staphylococcus aureus and remained persistently positive despite antibiotic
therapy. At surgical exploration, the popliteal artery had essentially been
disintegrated by the infection, with only visible stent graft maintaining
arterial continuity. Acute stent graft infections are rare and must be managed
promptly to reduce morbidity.
PMID- 29349382
TI - Intravascular ultrasound as a novel tool for the diagnosis and targeted treatment
of functional popliteal artery entrapment syndrome.
AB - Functional popliteal artery entrapment syndrome can be difficult to diagnose, as
the imaging modalities presently employed are designed to detect anatomic
entrapment. We describe a novel imaging technique to aid in diagnosis in this
cohort. A 22-year-old cyclist presented with exercise-limiting claudication.
Magnetic resonance angiography with provocative maneuvers was nondiagnostic.
Digital subtraction angiography revealed long-segment occlusion of the popliteal
artery with plantar flexion; however, the specific site of compression remained
unclear. Intravascular ultrasound allowed specific localization of compression
and further confirmed the diagnosis. Thus, we report this as an adjunctive
imaging modality to definitively diagnose functional popliteal artery entrapment
syndrome and to assist in operative planning.
PMID- 29349383
TI - Endovascular extraction of a migrated large self-expanding laser-cut renal venous
stent from the right ventricle.
AB - Endovascular stent placement for decompression of an entrapped left renal vein
(LRV) between the aorta and superior mesenteric artery is an alternative to
surgical decompression for treating the nutcracker syndrome. However, an
interventional approach may be challenging because of the unfavorable
configuration of the LRV, leading to insufficient stent anchoring. We provide a
case of a life-threatening stent migration from the LRV into the right ventricle
2 days after stent placement and its endovascular retrieval.
PMID- 29349384
TI - Acute hemifacial ischemia as a late complication of carotid stenting.
AB - Concerns about carotid artery stenting (CAS) center primarily on procedural
complications like acute occlusion, stroke, and long-term intrastent restenosis.
External carotid artery (ECA) thrombosis is observed during CAS follow-up, but it
often remains asymptomatic or, at worst, results in jaw claudication. We report
here a case of late occlusion of the ECA after CAS with symptoms of acute
homolateral facial ischemia as well as pain, cyanosis, tongue numbness, and skin
coldness. The patient was submitted to local thrombolysis and balloon angioplasty
with regression of symptoms after recanalization. With this report, we add a
caveat about blockage of the ECA ostium during CAS.
PMID- 29349385
TI - Novel, non-gadolinium-enhanced magnetic resonance imaging technique of pedal
artery aneurysms.
AB - Non-gadolinium-enhanced magnetic resonance angiography (nMRA) is a noninvasive,
contrast-free imaging modality used for visualizing pedal arterial anatomy. We
report application of the nMRA technique for detailed arterial imaging in a
patient with dorsalis pedis aneurysm. Compared with digital subtraction
angiography, we demonstrate that nMRA provides sufficient arterial detail needed
to develop a complex operative plan before vascular intervention without risk of
contrast agent or ionizing radiation exposure.
PMID- 29349386
TI - Successful use of retrograde branched extension limb assembling technique in
endovascular repair of pararenal abdominal aortic aneurysm.
AB - Surgeon-modified retrograde branched extension limb assembling technique and
bridged endografts were successfully used to exclude an asymptomatic pararenal
abdominal aortic aneurysm and to reconstruct the superior mesenteric artery and
bilateral renal arteries in a case with high-grade celiac artery stenosis,
nondilated aorta above the superior mesenteric artery, and large lumen below the
renal arteries. In patient-specific models for hemodynamics analysis, enhanced
flow diversion to visceral arteries up to 6-month follow-up confirmed treatment
feasibility; however, endograft configurations could be improved to avoid sharp
corners at bifurcations, thereby ensuring smooth flow transport and possibly
reducing risk for endograft narrowing or the development of thrombosis.
PMID- 29349387
TI - Regarding "Endograft limb trimming and resheathing can be an alternative for
emergent aortic repair without adequate stent graft availability".
PMID- 29349388
TI - Atypical infrarenal aortic coarctation.
PMID- 29349389
TI - Reply.
PMID- 29349390
TI - Durability of the Viabahn stent graft after axillary artery pseudoaneurysm
exclusion.
AB - Pseudoaneurysm formation caused by iatrogenic arterial injury during a regional
anesthetic block is a rare complication. We report a case of a 56-year-old male
patient who developed an axillary artery pseudoaneurysm caused by brachial plexus
block performed for an upper extremity dialysis access operation. Successful
repair of this pseudoaneurysm was achieved with endovascular stent graft
exclusion. The repaired axillary artery with the stent graft remained patent
after 10 years of follow-up. The successful long-term patency of this treatment
and a strategy to potentially avoid this complication are discussed.
PMID- 29349391
TI - Inguinal pain and fullness due to an intravascular leiomyoma in the external
iliac vein.
AB - Intravascular leiomyomatosis (IVL) is a benign smooth muscle tumor that evolves
from the pelvic veins and can spread to the central veins and heart. Cardiac
involvement is the most commonly reported presentation. Initial diagnosis is
difficult, and IVL is commonly misdiagnosed as thrombus or atrial myxoma.
Appropriate imaging and a high clinical suspicion are required for accurate
diagnosis. We report a rare case of IVL in the external iliac vein that recurred
4 years after hysterectomy. Only four cases have been reported in the literature
to involve the external iliac vein as it has no direct connection to pelvic
venous drainage.
PMID- 29349392
TI - Ovarian hyperstimulation syndrome as a rare cause of acute bilateral limb and
renal ischemia.
AB - Ovarian hyperstimulation syndrome (OHS) is a rare and potentially fatal
condition, particularly when it is associated with arterial thromboembolic
events. We present a case of acute ischemia of both lower limbs and left kidney
due to OHS. The clinical presentation included voluminous ascites, pleural
effusion, and significant ovarian enlargement. Subsequently, bilateral severe
acute limb ischemia and left kidney segmental infarction were established.
Surgical thromboembolectomy and muscle debridement of the lower limbs were
necessary, and the patient recovered with partial limitations. A high index of
suspicion and timely treatment are essential to minimize consequences of arterial
thrombosis associated with OHS.
PMID- 29349393
TI - Posterior tibial artery aneurysm in a child with SMAD3 mutation.
AB - Peripheral arterial aneurysms in children are uncommon. We report a 6-year-old
boy who developed a right posterior tibial artery aneurysm with symptoms
including pain and pulsatile tenderness. His genetic testing revealed a SMAD3
mutation, a condition associated with familial aortic aneurysm, early-onset of
osteoarthritis, and peripheral aneurysms. The posterior tibial artery aneurysm
was treated with surgical resection and primary anastomosis. The patient remained
free of symptoms or aneurysm recurrence in his tibial artery 2 years later. This
represents the first reported case of pediatric tibial artery aneurysm linked to
a SMAD3 mutation.
PMID- 29349394
TI - Infrared thermography in the diagnosis and management of vasculitis.
AB - Vasculitis is a clinical condition with associated diagnostic challenges due to
nonspecific symptoms and lack of a confirmatory imaging modality. We report a
case of a 39-year-old female patient who developed generalized malaise, lethargy,
and headache. Laboratory evaluation showed elevated inflammatory markers.
Conventional imaging studies including computed tomography and carotid duplex
ultrasound were unremarkable. Infrared thermography revealed enhanced
thermographic signals in the left carotid artery and aortic arch. Corticosteroid
therapy was commenced, and the patient responded well. Follow-up infrared
thermography at 6 months showed complete resolution of the thermographic pattern,
and the patient remained symptom free.
PMID- 29349395
TI - Delayed migration of a thrombosed aortic endograft within a thrombosed aneurysm
sac resulting in continued sac expansion and rupture.
AB - We present the case of delayed migration of a thrombosed aortic endograft within
a thrombosed aneurysm sac that expanded and ruptured. Dilation of the aortic neck
likely led to endograft migration and exposure of the occluded endograft and
aneurysm sac to systemic pressure. Although no endoleak was identified, a key
finding on ultrasound showed mobility of the sac thrombus. This may be an
indicator of flow within the sac that may predict potential for rupture. Despite
thrombosis of the aortic sac and endograft, the risk of rupture still lingers,
and thus continued surveillance of occluded endografts may be prudent.
PMID- 29349396
TI - Isolated lower extremity vasculitis leading to progressive critical limb
ischemia.
AB - Giant cell arteritis is a large- and medium-vessel vasculitis that has been
described as a systemic disease process with disseminated vessel involvement.
Advances in vascular imaging techniques have demonstrated that involvement of the
large vessels of the upper and lower limbs may be more prevalent than was once
thought, although the clinical implications of this are unknown. Isolated lower
extremity claudication without systemic or classic cranial symptoms, especially
as a primary manifestation of giant cell arteritis, is rare. We present the case
of a patient with isolated bilateral limb claudication that rapidly progressed to
critical limb ischemia requiring urgent surgical intervention after steroid
therapy. Our patient has consented to the publication of this report.
PMID- 29349397
TI - Femoral artery embolization of a thoracic stray bullet.
AB - Arterial bullet embolization after a thoracic gunshot wound represents a
diagnostic and therapeutic challenge. The absence of an apparent exit wound
should alert the clinician. Cardiac bullet injuries are mostly fatal. However, in
some cases, patients may remain stable, and conservative management can be an
acceptable strategy. We present a case report of a 7.62- * 39-mm thoracic stray
bullet that embolized to the femoral artery.
PMID- 29349398
TI - Unexplained rupture after endovascular aneurysm repair.
AB - We present a case of a 70-year-old man who was admitted with rupture of an
abdominal aneurysm 4 years after endovascular aneurysm repair. He was compliant
with yearly follow-up computed tomography angiography. One month earlier, his
computed tomography angiogram showed perfect exclusion of the aneurysm and no
endoleak. We explanted the stent graft and confirmed effective sealing, and the
graft was intact. We found no signs of infection during 2 years of follow-up.
This rupture is nonpredictable and unexplained and illustrates that unremarkable
imaging does not guarantee prevention of rupture. This case shows that the
ultimate failure of endovascular aneurysm repair cannot be prevented despite
surveillance protocols.
PMID- 29349399
TI - Subclavian steal syndrome without subclavian stenosis.
AB - Subclavian steal syndrome (SSS) has been well described in the setting of
subclavian stenosis. We describe an unusual case of SSS caused by a high-flow
arteriovenous dialysis fistula in the absence of subclavian stenosis, provide a
review of the literature, and propose that arteriovenous fistula-induced SSS is
an underdiagnosed cause of syncope in this population of patients.
PMID- 29349400
TI - Single-session total endovascular iliocaval reconstruction with stent grafting
for the treatment of inferior vena cava agenesis and concurrent iliac venous
aneurysm rupture.
AB - Iliac venous aneurysms are rare vascular abnormalities that may be manifested by
abdominal masses, pelvic tenderness, or hypovolemia and may lead to rupture,
thrombosis, pulmonary embolism, paradoxical embolism, or death. Inferior vena
cava agenesis, like venous aneurysm, is an uncommon condition that may present
with deep venous thrombosis. This report describes a patient with inferior vena
cava agenesis and iliac venous aneurysm rupture treated with emergent iliocaval
reconstruction and endovascular stent graft placement.
PMID- 29349401
TI - Staged reconstruction of the inferior vena cava after gunshot injury.
AB - A 23-year-old man with a gunshot injury to the abdomen and cardiac arrest
requiring emergency department thoracotomy had a transection of the distal
inferior vena cava (IVC) and small bowel injury. Because of persistent
hemorrhagic shock, the IVC was ligated. During the next 3 days, he developed
worsening bilateral leg edema. He was taken back for reanastomosis of his small
bowel and reconstruction of the IVC using autologous femoral vein harvested from
the right leg. We think that patients requiring ligation of the vena cava with
worsening leg edema can benefit from a staged reconstruction of the IVC.
PMID- 29349402
TI - Transposition of the persistent sciatic artery for lower limb revascularization
after resection of an embolizing proximal sciatic artery aneurysm.
AB - We present a novel surgical technique for lower limb revascularization after
resection of an aneurysm of the persistent sciatic artery that had led to
recurrent peripheral embolization and severe ischemia. The superficial femoral
artery in this patient was hypoplastic, and the sciatic artery continued into the
popliteal artery as the source of blood supply to the lower leg. For
revascularization, we used the distally pedicled healthy two-thirds of the
persistent sciatic artery, transposed it from its posterior position to a nearly
anatomic anteromedial position, and anastomosed it to the proximal superficial
femoral artery.
PMID- 29349403
TI - A novel hybrid left renal vein transposition and endovascular stenting technique
for the treatment of posterior nutcracker syndrome.
AB - Posterior nutcracker syndrome occurs when a retroaortic left renal vein becomes
compressed between the abdominal aorta and the lumbar spine. Although open
surgical approaches remain the treatment of choice, endovascular stenting has
been used successfully. We describe a case of a 28-year-old man who presented
with microscopic hematuria, left-sided flank pain, and testicular swelling.
Computed tomography findings were consistent with posterior nutcracker syndrome.
He underwent a novel hybrid operation that included left renal vein transposition
followed by endovascular stenting. Repeated imaging at 3 and 12 months revealed a
patent stent with complete resolution of symptoms.
PMID- 29349404
TI - External jugular vein thrombosis secondary to deep tissue neck massage.
AB - An 85-year-old man presented with an acute asymptomatic lateral neck mass in the
context of deep tissue neck massages during the past year. He was referred to
vascular surgery after an ultrasound examination of the neck revealed a thrombus
in the external jugular vein. His past medical history and comorbidities were
noncontributory. A multidisciplinary team of vascular surgeons and hematologists
did not recommend any anticoagulation, given that the patient did not have any
risk factors for thrombosis as well as normal D-dimer levels. The patient was
maintained on his previous dose of aspirin (81 mg daily).
PMID- 29349405
TI - Pseudoaneurysm of the external iliac artery is a rare late complication after
total hip arthroplasty.
AB - Vascular injury as a delayed complication of total hip arthroplasty (THA) is
rare. We present a case of pseudoaneurysm of the external iliac artery due to
chronic irritation from a prominent bone spicule occurring 2 years after revision
THA. We successfully managed the patient with open repair, and there has been no
sign of recurrence in the 2 years since the previous surgery. This report
suggests that patients who have undergone THA should be followed up carefully and
assessed for vascular injuries even after a substantial time.
PMID- 29349406
TI - Thrombolytic therapy for critical limb ischemia in a Jehovah's Witness with
severe anemia.
AB - A patient's refusal to receive blood products can pose both clinical and ethical
challenges to the surgeon. In this report, we review the case of a Jehovah's
Witness presenting with critical lower limb ischemia and severe anemia for whom
the decision of whether to perform thrombolytic therapy was complicated by his
refusal to accept blood products. The case demonstrates that thrombolytic therapy
can produce favorable results in severely anemic patients even when transfusion
is not an option. We conclude that offering thrombolytic therapy in this context
is a reasonable therapeutic option from both a clinical and ethical perspective.
PMID- 29349407
TI - Endovascular recanalization of occluded superior mesenteric artery using
retrograde access through the inferior mesenteric artery.
AB - Symptomatic occlusion of the superior mesenteric artery can be treated by open
repair, hybrid procedure, or endovascular revascularization. In most cases,
endovascular procedures are done by the antegrade approach. We report a case of a
67-year-old woman who presented with acute-on-chronic mesenteric ischemia
successfully treated by retrograde endovascular recanalization of an occluded
common hepatomesenteric trunk through the inferior mesenteric artery and arc of
Riolan.
PMID- 29349408
TI - Infolding of fenestrated endovascular stent graft.
AB - We report a case of infolding of a fenestrated stent graft involving the visceral
vessel segment after a juxtarenal abdominal aorta aneurysm repair. The patient
remains free of any significant endoleak, and the aortic sac has shown
regression. The patient remains asymptomatic, with no abdominal pain, with normal
renal function, and without ischemic limb complications. We hypothesize that
significant graft oversizing (20%-30%) with asymmetric engineering of the
diameter-reducing ties may have contributed to the infolding. Because of the
patient's asymptomatic nature and general medical comorbidities, further
intervention was deemed inappropriate as the aneurysmal sac is regressing despite
the infolding.
PMID- 29349409
TI - Salvage of bilateral renal artery occlusion after endovascular aneurysm repair
with open splenorenal bypass.
AB - We report renal salvage maneuvers after accidental bilateral renal artery
coverage during endovascular aneurysm repair of an infrarenal abdominal aortic
aneurysm. A 79-year-old man with an infrarenal abdominal aortic aneurysm was
treated with endovascular aneurysm repair. Completion angiography demonstrated
coverage of the renal arteries. Several revascularization techniques were
attempted, including endograft repositioning and endovascular stenting through
the femoral and brachial approach. The patient eventually underwent open
splenorenal bypass with a Y Gore-Tex graft (W. L. Gore & Associates, Flagstaff,
Ariz). After 3 months, computed tomography showed no evidence of endoleak and
patent renal arteries. Renal function was well maintained, and the patient did
not require dialysis.
PMID- 29349410
TI - Rupture of abdominal aortic aneurysm between early and late phases of enhanced
computed tomography.
PMID- 29349411
TI - Takayasu arteritis with middle aortic syndrome and mesenteric ischemia treated by
aortic stenting.
AB - A 48-year-old woman suffering from Takayasu arteritis presented with middle
aortic syndrome consisting of abdominal pain, refractory hypertension with
pulmonary edema and pleural effusions, and lower limb ischemia. She failed to
improve with high-dose steroid therapy and underwent endovascular stenting of two
severe stenoses in the supraceliac and infrarenal aorta. Her symptoms resolved
and hypertension improved after the procedure.
PMID- 29349412
TI - Treatment of a symptomatic intrathoracic internal carotid artery.
AB - Intrathoracic common carotid artery bifurcations are an anatomic anomaly with
such rarity that only six cases have been reported to date. The true incidence of
and preferred treatment options for a diseased intrathoracic common carotid
artery bifurcation or internal carotid artery (ICA) have not been clearly
described. This case report describes a 72-year-old man who experienced a
postoperative right hemispheric stoke after an aortic valve replacement,
radiofrequency maze procedure, and left atrial appendage clip. Postoperative
cerebrovascular evaluation revealed a severely diseased intrathoracic ICA that
was treated by ligation of the diseased proximal ICA and transposition of the
distal ICA to the disease-free external carotid artery. The patient provided
written consent to present the history, data, and images in this manuscript.
PMID- 29349413
TI - Safety and efficacy of a modified HeRO dialysis device in achieving early graft
cannulation: A single-institution experience.
AB - Hemodialysis Reliable Outflow (HeRO) grafts (Merit Medical Systems, Inc, South
Jordan, Utah) provide a means for access in catheter-dependent hemodialysis
patients but typically require several weeks for tissue incorporation. Modifying
the HeRO graft with an ACUSEAL graft (W. L. Gore & Associates, Newark, Del) can
allow immediate cannulation, thus reducing catheter dependence time and its
associated complications. A retrospective review of patients at our institution
from 2013 to 2016 who underwent placement of a modified HeRO dialysis system with
ACUSEAL graft was performed. Complications and outcomes were analyzed, with
patency rates and hours to successful cannulation being major end points.
Modified HeRO grafts were successfully placed in 10 catheter-dependent patients.
Postoperative complications included two thromboses and one hematoma. At 6 months
of follow-up, mean time to graft cannulation was 33.7 hours, with 100% success;
the primary and secondary patency rates were 70% and 90%, respectively. Our
modification allows an accelerated use of the HeRO system, reducing catheter
dependence time with acceptable postoperative complications and patency rates.
PMID- 29349414
TI - Idiopathic radial artery true aneurysm.
PMID- 29349415
TI - A track made by organized thrombus after catheter fragment removal mimicking a
remnant catheter in the popliteal artery.
PMID- 29349416
TI - Acute aortic occlusion secondary to aortic endograft migration and collapse.
PMID- 29349417
TI - Emergent endovascular repair of a ruptured giant internal iliac artery aneurysm
using an inverted iliac limb endograft.
PMID- 29349418
TI - Femoral artery embolism of bullet after thoracic gunshot wound.
PMID- 29349419
TI - Covered endovascular repair of the paravisceral aorta.
AB - Open aortic repair is considered the "gold standard" treatment for aortic
occlusive disease. We present the case of an 83-year-old patient with refractory
hypertension caused by paravisceral aortic stenosis including both renal arteries
and the superior mesenteric artery. We planned an endovascular approach and
treated the patient with parallel stent grafts in the paravisceral aorta. At 1.5
years after the operation, the patient was free of hypertensive episodes. Covered
endovascular repair of the paravisceral aorta may be a valuable alternative to
open aortic repair in patients unfit for open surgery. More research is needed to
evaluate the long-term effects of this technique.
PMID- 29349420
TI - Common carotid artery pseudoaneurysm secondary to Mycobacterium tuberculosis
treated with resection and reconstruction with saphenous vein graft.
AB - Extracranial carotid artery aneurysms secondary to Mycobacterium tuberculosis
infection are exceedingly rare. Despite an uncommon location and offending
pathogen, the treatment paradigm follows that of all mycotic aneurysms. We report
the case of a right common carotid artery pseudoaneurysm caused by a tuberculous
infection, successfully treated with antibiotics, resection, and autologous
interposition graft.
PMID- 29349421
TI - Large-diameter inferior mesenteric artery in a case involving a ruptured common
iliac artery aneurysm.
PMID- 29349422
TI - Hybrid management of a ruptured right subclavian artery aneurysm dissection.
AB - Aberrant right subclavian artery is the most common congenital malformation of
the aortic arch (0.4%-2.0%). Aneurysms of aberrant subclavian arteries are
extremely rare. This results in little experience with their treatment. We
describe a case of a patient who presented to the emergency department with a
dissection of an aberrant right subclavian artery that later progressed to
rupture. Besides hemodynamic instability, this caused an acute superior vena cava
syndrome, making airway control difficult. In the operating room, we obtained
proximal control through thoracic endovascular aortic repair; median sternotomy
was performed for distal control and evacuation of massive hemomediastinum.
PMID- 29349423
TI - Ruptured giant popliteal artery aneurysm.
PMID- 29349424
TI - Symptomatic giant carotid artery aneurysm.
PMID- 29349425
TI - Assessment of lower extremity ischemia using smartphone thermographic imaging.
AB - Conventional diagnostic modalities for assessing arterial circulation or tissue
perfusion include blood pressure measurement, ultrasound evaluation, and contrast
based angiographic assessment. An infrared thermal camera can detect infrared
radiation energy from the human body, which generates a thermographic image to
allow tissue perfusion analysis. We describe a smartphone-based miniature thermal
imaging system that can be used as an adjunctive imaging modality to assess
tissue perfusion. This smartphone-based camera device is noninvasive, simple to
use, and cost-effective in assessing patients with lower extremity tissue
perfusion. Assessment of patients with lower extremity arterial ischemia can be
performed by a variety of diagnostic modalities, including ankle-brachial index,
absolute systolic ankle or toe pressure, transcutaneous oximetry, arterial
Doppler waveform, arterial duplex ultrasound, computed tomography scan, arterial
angiography, and thermal imaging. We herein describe a noninvasive imaging
modality using smartphone-based infrared thermography.
PMID- 29349427
TI - An unusual cause of cruralgia.
PMID- 29349426
TI - Development of a pulsatile, tissue-based, versatile vascular surgery simulation
laboratory for resident training.
AB - Simulation in surgery is becoming an important component of surgical education.
Training on bench top models has been demonstrated to improve technical skills.
The objective of our project was to create a vascular surgery simulation model.
The simulation model consists of a platform, artificial blood reservoir,
artificial blood, inflow and outflow limbs, electric motor, battery, pulse
generator, and cryopreserved vessel. Three different vascular surgery simulation
stations were created: carotid endarterectomy with shunting and patch
angioplasty, arterial bypass, and arteriovenous graft formation. A scientific
study involving surgical residents will need to be undertaken to determine
whether this simulator has intermodal transferability.
PMID- 29349428
TI - Hybrid repair of a large pseudoaneurysm of the proximal right subclavian artery
in a Marfan patient.
AB - A pseudoaneurysm of the proximal right subclavian artery is rare and most
commonly caused by penetrating or blunt trauma. We report a case of a Marfan
patient with a large iatrogenic pseudoaneurysm of the right subclavian artery,
induced by a puncture lesion during central venous catheter placement for an
elective endovascular thoracic aortic procedure. The patient was successfully
treated with a hybrid approach, which consisted of endovascular coiling and
balloon occlusion of the adjacent vessels, followed by open surgical exploration
and uneventful closure of the puncture hole with the use of bovine pericardium
reinforced sutures.
PMID- 29349429
TI - Repair of a mycotic abdominal aortic aneurysm in a neonate using an everted
jugular vein patch.
AB - A 43-day-old boy presented with bacteremia after umbilical artery
catheterization. Duplex ultrasound examination revealed a 1.1- * 1.6-cm mycotic
infrarenal aortic aneurysm and an incidental asymptomatic occluded right common
iliac artery. Resection and repair were completed by creating an everted, double
layered internal jugular vein patch. Screening ultrasound examination 10 months
postoperatively demonstrated successful repair.
PMID- 29349430
TI - Surgical repair of a celiac artery aneurysm using a sutureless proximal
anastomosis device.
AB - Some celiac artery aneurysms are not suitable for endovascular therapy. We
describe the case of a 63-year-old man with a celiac trunk aneurysm extending to
the hepatosplenic bifurcation. The aneurysm was resected and oversewn at the
origin from the abdominal aorta. A saphenous vein bypass from the supraceliac
aorta to the celiac artery bifurcation was performed using a sutureless
anastomotic device (PAS-Port system; Cardica, Redwood City, Calif) to create the
proximal anastomosis, eliminating the need for aortic clamping. This system is
thought to make direct proximal aortic anastomosis safe and easy in patients
requiring surgical reconstruction of celiac artery aneurysms.
PMID- 29349431
TI - Complete robotic repair of a renal artery aneurysm.
AB - Although the majority of renal artery aneurysms require only observation, those
that require treatment have been addressed primarily surgically or
endovascularly. We report a case of surgical resection of a large, symptomatic
renal artery aneurysm from an entirely robotic approach.
PMID- 29349432
TI - Aortic arch banding procedure for proximal type I endoleak after thoracic
endovascular aneurysm repair with the chimney technique.
AB - An aortic arch banding procedure was performed on an 82-year-old man for
treatment of proximal type I endoleaks 2 days after he had undergone emergency
thoracic endovascular aortic repair with the chimney technique for a ruptured
aortic arch aneurysm. Contrast-enhanced computed tomography after the second
procedure demonstrated significant shrinkage of the aneurysmal sac as well as a
complete disappearance of the endoleaks. The basic concept of this technique is
to treat the type IA endoleak, including possible gutter endoleaks, by creating a
new proximal seal zone distal to the chimney graft using a banding technique.
PMID- 29349433
TI - Popliteal artery entrapment syndrome presenting as acute limb ischemia in
pregnancy.
AB - Popliteal artery entrapment syndrome typically causes calf claudication in young
active adults. Acute limb ischemia from popliteal artery thrombosis,
embolization, or aneurysmal degeneration is less common. Chronic compression,
histologic changes, and predisposing factors, such as vigorous exercise or
hypercoagulability, play a role in these cases. We present the case of a 32-year
old pregnant woman with acute limb ischemia found to have popliteal artery
thrombosis as a result of popliteal artery entrapment syndrome. Although many
imaging modalities are available, pregnancy creates a unique situation in which
consideration of irradiation and exposure to contrast material is important in
diagnosis and treatment.
PMID- 29349434
TI - A novel application of the culotte stent technique to bail out a jailed common
iliac artery.
AB - Implanting a self-expandable stent at the ostium of the common iliac artery (CIA)
may lead to coverage of the orifice of the contralateral CIA. Here, we describe a
novel application of the culotte stent technique using a balloon-expandable stent
to bail out an ostial stenotic legion of a jailed CIA due to prior self
expandable stent placement. The bilateral CIAs were revascularized by culotte
stenting, and patency of the stents was confirmed 3 years after the procedure.
The culotte stent technique was successfully applied to an ostial stenotic lesion
of a jailed CIA.
PMID- 29349435
TI - Emergency endovascular coiling of a ruptured giant splenic artery aneurysm.
AB - Splenic artery aneurysms (SAAs) are the third most common abdominal aneurysm.
Endovascular treatment of SAAs is preferred, and coiling is the most commonly
used technique. Ruptured giant (>5 cm) SAAs are usually treated with open surgery
including splenectomy. We present a rare case of a ruptured 15-cm giant SAA in an
84-year-old woman treated successfully with emergency endovascular coiling. To
our knowledge, this is one of the few reports of emergency endovascular treatment
for ruptured giant SAA.
PMID- 29349436
TI - Superficial temporal artery aneurysm associated with immunoglobulin G4-related
disease.
AB - A 68-year-old man was admitted because of a pulsatile mass and pain in the left
temporal region, and computed tomography demonstrated the superficial temporal
artery aneurysm. He underwent aneurysmectomy, and pathologic investigation
revealed marked thickness of the adventitia with substantial plasmacyte
infiltration. On immunoglobulin G4 (IgG4) immunohistochemistry, IgG4-positive
lymphocytes were scattered in the adventitia, and biochemical tests revealed
elevation of IgG4 (200 mg/dL). The case satisfied the criteria for both giant
cell arteritis and IgG4-related disease (IgG4-RD). This case report suggested
that IgG4-RD can occur in the superficial temporal artery and that IgG4-RD may
partially overlap with a subtype of giant cell arteritis.
PMID- 29349437
TI - Staged endovascular repair of an abdominal aortic aneurysm adjacent to a chronic
high-flow iliocaval traumatic arteriovenous fistula.
AB - Large-vessel chronic traumatic arteriovenous fistulas are a rare complication
after trauma. Delayed presentation can consist of one or more features of high
output cardiac failure, pulsatile abdominal mass, bruit, limb ischemia, and
venous congestion. We describe a patient with a complex iliocaval fistula
secondary to a remote gunshot wound associated with a large 8.5-cm aortic
aneurysm. Informed consent of the patient was obtained for publication of the
case.
PMID- 29349438
TI - Idiopathic internal mammary artery aneurysm in the setting of aberrant right
subclavian artery.
AB - Aneurysms of the internal mammary artery are extremely rare. Immediate treatment
is necessary because of the high risk of rupture that can be life-threatening.
Here we describe a case of idiopathic internal mammary artery aneurysm in a 54
year-old woman in the setting of aberrant right subclavian artery. The aneurysm
was successfully treated with coil embolization without complications.
PMID- 29349439
TI - Protein C deficiency resulting from two mutations in PROC presenting with
recurrent venous thromboembolism.
AB - Hereditary protein C (PC) deficiency is an autosomal dominant disorder associated
with a high risk of venous thromboembolism (VTE). Here we report a case of
inherited PC deficiency associated with recurrent deep venous thrombosis. Two
mutations were revealed in PROC (c.1152C>G, p.N384K and c.1207G>T, p.G403W) by
genetic testing. Results from this case suggest that the inherited PC deficiency
due to the PROC mutations may cause recurrent VTE. Long-term anticoagulant
therapy may be appropriate for these patients with recurrent VTE and hereditary
PC deficiency.
PMID- 29349440
TI - Preservation of internal iliac arteries during endovascular aneurysm repair using
"eye of the tiger" technique.
AB - Parallel endografts were introduced as a way to expand endovascular repair of
aneurysms involving branch vessels. However, endoleaks as a result of the gutters
between the parallel endografts made this technique less favorable. The "eye of
the tiger" technique was introduced to reduce the gutters between the parallel
endografts proximally in the aorta. We report endovascular repair of infrarenal
abdominal aortic aneurysm using eye of the tiger technique distally to preserve
the internal iliac arteries.
PMID- 29349441
TI - Association between sn-2 fatty acid profiles of breast milk and development of
the infant intestinal microbiome.
AB - Increasing evidence shows that host diet and gut microbes are related. Previous
studies have shown the effects of specific dietary fatty acids (FAs) on
intestinal microbiota, but little is known about the effect of the
stereospecifically numbered sn-2 position in triglycerides (TG) of human milk on
the gut microbiome of infants. This study aimed at examining possible effects of
sn-2 FAs of human milk on the gut microbial development of breastfeeding babies.
Sn-2 FAs and intestinal microbiota were assessed by GC-MS and high-throughput 16S
rRNA sequencing, respectively. The results showed that breast milk from mothers
in China contained ten major sn-2 FAs dominated by palmitic acid (C16:0, 54.42%),
oleic acid (C18:1 n-9, 14.95%), linoleic acid (LA, C18:2 n-6, 12.81%), myristic
acid (C14:0, 4.50%) and C12:0 (3.17%). Total long chain unsaturated fatty acids
(LCUFA) decreased from colostrum to mature milk, while total saturated fatty
acids (SFA) showed no significant difference during lactation. A significant
association between sn-2 FAs in milk and infant gut microbiota was found between
decanoic acid (C10:0), myristic acid (C14:0), stearic acid (C18:0), C16:0,
arachidonic acid (AA, C20:4 n-6), docosahexaenoic acid (DHA, C22:6 n-3) with
Bacteroides, Enterobacteriaceae, Veillonella, Streptococcus, and Clostridium.
These microbes were involved in short-chain fatty acid (SCFA) production and
other functions, and significantly increased at 13-15 d after breastfeeding was
initiated. C16:0 and DHA were relevant to most of the microbes. This study
demonstrated the relatively steady profiles of sn-2 FAs in breast milk and gut
microbiota of infants, together with their correlation during the breastfeeding
period. The above results provided important information for designing the
configuration of FAs in next-generation formulas for Chinese infants.
PMID- 29349442
TI - Impact of Nb vacancies and p-type doping of the NbCoSn-NbCoSb half-Heusler
thermoelectrics.
AB - The half-Heuslers NbCoSn and NbCoSb have promising thermoelectric properties.
Here, an investigation of the NbCo1+ySn1-zSbz (y = 0, 0.05; 0 <= z <= 1) solid
solution is presented. In addition, the p-type doping of NbCoSn using Ti and Zr
substitution is investigated. Rietveld analysis reveals the gradual creation of
Nb vacancies to compensate for the n-type doping caused by the substitution of Sb
in NbCoSn. This leads to a similar valence electron count (~18.25) for the
NbCo1+ySn1-zSbz samples (z > 0). Mass fluctuation disorder due to the Nb
vacancies strongly decreases the lattice thermal conductivity from 10 W m-1 K-1
(z = 0) to 4.5 W m-1 K-1 (z = 0.5, 1). This is accompanied by a transition to
degenerate semiconducting behaviour leading to large power factors, S2/rho = 2.5
3 mW m-1 K-2 and figures of merit, ZT = 0.25-0.33 at 773 K. Ti and Zr can be used
to achieve positive Seebeck values, e.g. S = +150 MUV K-1 for 20% Zr at 773 K.
However, the electrical resistivity, rho323K = 27-35 mOmega cm, remains too large
for these materials to be considered useful p-type materials.
PMID- 29349443
TI - Large valley polarization in monolayer MoTe2 on a magnetic substrate.
AB - On the basis of valley degree of freedom, there would be immense potential
application in valleytronics. Introducing magnetism into triangular or hexagonal
lattices is a promising route to realize valley polarization, which is
indispensable for applying the valley degree of freedom. In this study, we
explored valley polarization by depositing a heterostructure of a MoTe2 monolayer
on the (0 0 1) surface of an antiferromagnetic RbMnCl3 substrate. First
principles-calculations showed that due to proximity-induced Zeeman effects, the
MoTe2 monolayer was drastically magnetized by the topmost Mn layer in the
substrate and a very large valley splitting (about 109 meV) was achieved. Using
an effective Hamiltonian model, the effect of the competition of the spin-orbit
coupling (SOC) and exchange field in the system on the valley polarization was
also investigated. The magnitude of the valley splitting was found to be limited
by the smaller SOC value and the induced exchange field, providing information on
the enhancement of the valley polarization. A device rudiment with an anomalous
valley Hall effect is proposed.
PMID- 29349444
TI - Non-invasive force measurement reveals the number of active kinesins on a
synaptic vesicle precursor in axonal transport regulated by ARL-8.
AB - Kinesin superfamily protein UNC-104, a member of the kinesin-3 family, transports
synaptic vesicle precursors (SVPs). In this study, the number of active UNC-104
molecules hauling a single SVP in axons in the worm Caenorhabditis elegans was
counted by applying a newly developed non-invasive force measurement technique.
The distribution of the force acting on a SVP transported by UNC-104 was spread
out over several clusters, implying the presence of several force-producing units
(FPUs). We then compared the number of FPUs in the wild-type worms with that in
arl-8 gene-deletion mutant worms. ARL-8 is a SVP-bound arf-like small guanosine
triphosphatase, and is known to promote unlocking of the autoinhibition of the
motor, which is critical for avoiding unnecessary consumption of adenosine
triphosphate when the motor does not bind to a SVP. There were fewer FPUs in the
arl-8 mutant worms. This finding indicates that a lack of ARL-8 decreased the
number of active UNC-104 motors, which then led to a decrease in the number of
motors responsible for SVP transport.
PMID- 29349445
TI - Discovery of novel diarylpyrimidines as potent HIV-1 NNRTIs by investigating the
chemical space of a less explored "hydrophobic channel".
AB - A new series of diarylpyrimidines (DAPYs) were designed, synthesized and
evaluated as novel HIV-1 NNRTIs to further explore the chemical space surrounding
the "hydrophobic channel" of the NNRTI binding pocket (NNIBP), guided by the
comprehensive analysis of X-ray structural biology data of HIV-1 RT/NNRTI
complexes and molecular modeling. Encouragingly, most of the synthesized DAPYs
were found to be active against the HIV-1 wild-type (WT) strain with EC50 values
ranging from 3 nM to 63 nM, and displayed significantly reduced cytotoxicity
compared with etravirine (ETV) and rilpivirine (RPV). Among them, two most
promising compounds Z10 (EC50 = 3 nM) and Z13 (EC50 = 3 nM) showed equivalent
potency against the HIV-1 WT strain to the reference drugs efavirenz (EFV, EC50 =
3 nM) and ETV (EC50 = 3 nM). Notably, Z13 also showed the most potent activity
against HIV-1 mutant strains including K103N (EC50 = 10 nM), E138K (EC50 = 22 nM)
and RES056 (EC50 = 0.935 MUM). Against mutant strains Y181C, Y188L and F227L +
V106A, Z17 showed double-digit nanomolar inhibitory activity with EC50 values 27
nM, 98 nM and 30 nM, respectively. The structure-activity relationships (SARs)
and molecular docking studies provided important clues for further molecular
elaboration. Collectively, this study provides useful information to guide lead
optimization and drug discovery via the exploration of this seldom investigated
region.
PMID- 29349446
TI - Ameliorative role of camel whey protein and rosuvastatin on induced dyslipidemia
in mice.
AB - The incidence of obesity is rapidly increasing throughout the world. Dyslipidemia
is a major risk factor for a number of chronic diseases, including diabetes and
cardiovascular diseases. This work presents a novel approach to study the
activity of camel whey protein (WP) with antioxidant and anti-inflammatory
properties as a cheap dietary protein substance extracted from camel milk to
produce satiety and help in building muscles. Mice model suffering from
dyslipidemia as a result of feeding on high fat-cholesterol diet for 8 weeks were
administrated with either camel WP and/or rosuvastatin for 4 weeks. Dyslipidemia
revealed significant increase in anthropometrical measurements, levels of
glucose, insulin, cholesterol, triglycerides, low-density lipoprotein, total
leucocyte count, inflammatory cytokines and reactive oxygen species, accompanied
by a significant elevation in activating transcription factor-3 and inducible
nitric oxide synthase expressions. These alterations were correlated with a
profound reduction in high-density lipoprotein, peroxisome proliferator-activated
receptor alpha and adiponectin along with a decrease in liver and muscle
mitochondrial proteins. Rosuvastatin treatment to mice suffering from
dyslipidemia in combination with camel WP for 4 weeks ameliorated these
parameters. Notably, animals treated with both camel WP and rosuvastatin
exhibited a remarkable decrease in the incidence of dyslipidemia. In addition,
camel WP succeeded to overcome the therapeutic drawback posed from rosuvastatin
therapy alone with minimal side effects.
PMID- 29349447
TI - Theoretical study on the charge transport in single crystals of TCNQ, F2-TCNQ and
F4-TCNQ.
AB - 2,5-Difluoro-7,7,8,8-tetracyanoquinodimethane (F2-TCNQ) was recently reported to
display excellent electron transport properties in single crystal field-effect
transistors (FETs). Its carrier mobility can reach 25 cm2 V-1 s-1 in devices.
However, its counterparts TCNQ and F4-TCNQ (tetrafluoro-7,7,8,8
tetracyanoquinodimethane) do not exhibit the same highly efficient behavior. To
better understand this significant difference in charge carrier mobility, a
multiscale approach combining semiclassical Marcus hopping theory, a quantum
nuclear enabled hopping model and molecular dynamics simulations was performed to
assess the electron mobilities of the Fn-TCNQ (n = 0, 2, 4) systems in this work.
The results indicated that the outstanding electron transport behavior of F2-TCNQ
arises from its effective 3D charge carrier percolation network due to its
special packing motif and the nuclear tunneling effect. Moreover, the poor
transport properties of TCNQ and F4-TCNQ stem from their invalid packing and
strong thermal disorder. It was found that Marcus theory underestimated the
mobilities for all the systems, while the quantum model with the nuclear
tunneling effect provided reasonable results compared to experiments. Moreover,
the band-like transport behavior of F2-TCNQ was well described by the quantum
nuclear enabled hopping model. In addition, quantum theory of atoms in molecules
(QTAIM) analysis and symmetry-adapted perturbation theory (SAPT) were used to
characterize the intermolecular interactions in TCNQ, F2-TCNQ and F4-TCNQ
crystals. A primary understanding of various noncovalent interaction responses
for crystal formation is crucial to understand the structure-property
relationships in organic molecular materials.
PMID- 29349448
TI - A study on platinum(iv) species containing an estrogen receptor modulator to
reverse tamoxifen resistance of breast cancer.
AB - Several dual-action Tam-Pt(iv) complexes derived from tamoxifen (Tam) and
platinum(ii) drugs were designed and synthesized for targeting estrogen receptors
(ERs) and DNA. These novel compounds not only exhibited potent cytotoxicity
against breast cancer cells, but also reversed the tamoxifen resistance of TamR
MCF-7 cancer cells. Computational docking assays together with cellular uptake
data demonstrated that the ER ligand portion of these conjugates plays a
targeting role in ER-positive tumor cells and promotes the uptake of platinum via
an estrogen receptor-mediated pathway. A study on the preliminary mechanism of
the typical conjugate, complex 1, revealed that the Tam-Pt(iv) complex induced
apoptosis via the mitochondrial-dependent apoptosis pathway mediated through the
activation of caspase 3 and PARP proteins. These results suggested that the
conjugation of estrogen receptor modulators with the platinum moiety could
facilitate a selective enrichment of platinum in estrogen-positive tumors and
possibly broaden the scope of ER ligand clinical use to resistant breast tumors.
PMID- 29349449
TI - Local and global aromaticity in a molecular carbon nanobelt: insights from
magnetic response properties in neutral and charged species.
AB - The formation of carbon nanobelt made exclusively from fused benzene rings has
recently been achieved. Our results reveal an interesting shift from a local
aromatic character constrained in each of the six aromatic Clar sextets (6pi
electron circuit) to a global aromatic character in charged species (+2 and -2)
involving the overall pi-circuit from the molecular nanobelt. This demonstrates
the suppression of the local aromatic character in favor of a global aromaticity
by selecting the oxidation state of the carbon nanobelt, giving rise to a
shielding cone extended within the structure.
PMID- 29349450
TI - Complex patchy colloids shaped from deformable seed particles through capillary
interactions.
AB - We investigate the mechanisms underlying the reconfiguration of random aggregates
of spheres through capillary interactions, the so-called "colloidal recycling"
method, to fabricate a wide variety of patchy particles. We explore the influence
of capillary forces on clusters of deformable seed particles by systematically
varying the crosslink density of the spherical seeds. Spheres with a poorly
crosslinked polymer network strongly deform due to capillary forces and merge
into large spheres. With increasing crosslink density and therefore rigidity, the
shape of the spheres is increasingly preserved during reconfiguration, yielding
patchy particles of well-defined shape for up to five spheres. In particular, we
find that the aspect ratio between the length and width of dumbbells, L/W,
increases with the crosslink density (cd) as L/W = B - A.exp(-cd/C). For clusters
consisting of more than five spheres, the particle deformability furthermore
determines the patch arrangement of the resulting particles. The reconfiguration
pathway of clusters of six densely or poorly crosslinked seeds leads to
octahedral and polytetrahedral shaped patchy particles, respectively. For seven
particles several geometries were obtained with a preference for pentagonal
dipyramids by the rigid spheres, while the soft spheres do rarely arrive in these
structures. Even larger clusters of over 15 particles form non-uniform often
aspherical shapes. We discuss that the reconfiguration pathway is largely
influenced by confinement and geometric constraints. The key factor which
dominates during reconfiguration depends on the deformability of the spherical
seed particles.
PMID- 29349451
TI - On the turn-inducing properties of asparagine: the structuring role of the amide
side chain, from isolated model peptides to crystallized proteins.
AB - Asparagine (Asn) is a powerful turn-inducer residue, with a large propensity to
occupy the second position in the central region of beta-turns of proteins. The
present work aims at investigating the role of a local anchoring between the Asn
side chain and the main chain in this remarkable property. For this purpose, the
H-bonding patterns of an asparagine residue in an isolated protein chain fragment
forming a gamma- or a beta-turn have been determined using IR/UV double resonance
gas phase spectroscopy on laser-desorbed, jet-cooled short models in conjunction
with relevant quantum chemistry calculations. These gas phase data provide
evidence for an original double anchoring linking the Asn primary amide side
chain (SC), which adopts a gauche+ rotameric form, to its main chain (MC) local
environment. From both IR spectroscopic evidence (H-bond induced red shifts) and
quantum chemistry, Asn SC is found to behave as a stronger H-bond acceptor than
donor, resulting in stronger MC->SC H-bonds than SC->MC ones. These gas phase
structural data, relevant to a hydrophobic environment, have been used as a
reference to assess the anchoring taking place in high resolution crystallized
proteins of the Protein Data Bank. This approach reveals that, when the SC adopts
a gauche+ orientation, the stronger MC->SC bonds are preserved in many cases
whereas the SC->MC bonds are always disrupted, in qualitative agreement with the
gas phase ranking of these interactions. Most interestingly, when Asn occupies
the second position of central part of a beta-turn (i.e., the very turn-inducer
position), the MC->SC H-bonds are also disrupted and replaced by a water-mediated
SC to MC anchoring. Owing to the specific features of the hydrated Asn side
chain, we propose that it could be a turn precursor structure, able to facilitate
turn formation in the early events of the folding process.
PMID- 29349452
TI - Barriometry - an enhanced database of accurate barrier heights for gas-phase
reactions.
AB - The kinetics of many reactions are critically dependent upon the barrier heights
for which accurate determination can be difficult. From the perspective of
attaining such quantities using computational quantum chemistry, it is important
to appropriately validate routine and efficient methodologies such as density
functional theory (DFT) procedures. In the present study, we embark on the
journey of establishing diverse databases using a consistent high-level quantum
chemistry procedure, against which new and existing methodologies can be
assessed. Thus, we have used the composite protocol W3X-L to provide more than
100 refined reference values for existing databases [e.g., Y. Zhao and D. G.
Truhlar, J. Phys. Chem. A, 2005, 109, 5656] and additionally establish benchmark
data that are of interest to atmospheric and combustion chemists. While our
endeavor has just begun, assessment of various DFT methods with our existing
results lends support to the use of MN15 as an adequate method for general
kinetics applications. We also recommend the use of less-costly W2X and WG
composite protocols for obtaining adequately accurate reference thermochemical
values for larger molecular systems.
PMID- 29349453
TI - A QM/MM and QM/QM/MM study of Kerr, Cotton-Mouton and Jones linear birefringences
in liquid acetonitrile.
AB - QM/MM and QM/QM/MM protocols are applied to the ab initio study of the three
linear birefringences Kerr, Cotton-Mouton, and Jones, as shown by acetonitrile in
the gas and pure liquid phases. The relevant first-order properties as well as
linear, quadratic, and cubic frequency-dependent response functions were computed
using time-dependent Kohn-Sham density-functional theory with use of the standard
CAM-B3LYP functional. In the liquid phase, a series of room temperature (293.15
K) molecular dynamics snapshots were selected, for which averaged values of the
observables were obtained at an optical wavelength of 632.8 nm. The
birefringences were computed for electric and magnetic induction fields
corresponding to the laboratory setup previously employed by T. Roth and G. L. J.
A. Rikken in Phys. Rev. Lett., 2000, 85, 4478. Under these conditions,
acetonitrile is shown to exhibit a weak Jones response-in fact roughly 6.5 times
smaller than the limit of detection of the apparatus employed in the measurements
mentioned above. A comparison is made with the corresponding gas-phase results
and an assessment is made of the index of measurability, estimating the degree of
overlap of the three birefringences in actual measurements. For acetonitrile, it
is shown that this index is a factor of 3.6 and 6.7 larger than that of
methylcyclopentadienyl-Mn-tricarbonyl and cyclohexadienyl-Fe-tricarbonyl,
respectively-two compounds reported in Phys. Rev. Lett., 2000, 85, 4478 to
exhibit a strong Jones signal.
PMID- 29349454
TI - Adsorption and binding dynamics of graphene-supported phospholipid membranes
using the QCM-D technique.
AB - We report on the adsorption dynamics of phospholipid membranes on graphene-coated
substrates using the quartz crystal microbalance with dissipation monitoring (QCM
D) technique. We compare the lipid vesicle interaction and membrane formation on
gold and silicon dioxide QCM crystal surfaces with their graphene oxide (GO) and
reduced (r)GO coated counterparts, and report on the different lipid structures
obtained. We establish graphene derivative coatings as support surfaces with
tuneable hydrophobicity for the formation of controllable lipid structures. One
structure of interest formed is lipid monolayer membranes which were formed on
rGO, which are otherwise challenging to produce. We also demonstrate and monitor
biotin-avidin binding on such a membrane, which will then serve as a platform for
a wide range of biosensing applications. The QCM-D technique could be extended to
both fundamental studies and applications of other covalent and non-covalent
interactions in 2-dimensional materials.
PMID- 29349455
TI - On the H2 interactions with transition metal adatoms supported on graphene: a
systematic density functional study.
AB - The attachment of H2 to the full set of transition metal (TM) adatoms supported
on graphene is studied by using density functional theory. Methodology validation
calculations on the interactions of H2 with benzene and graphene show that any of
the vdW corrections under study, the Grimme D2, D3, D3 with Becke-Jonson damping
(D3BJ), and Tkatchenko-Scheffler methods, applied on the PBE functional, are
similarly accurate in describing such subtle interactions, with an accuracy of
almost 2 kJ mol-1 compared to experiments. The PBE-D3 results show that H2
physisorbs on especially stable d5 or d10 TMs. In other 5d metals, and the
rightmost 3d and 4d ones, H2 dissociates, and only for Y, Mn, Fe, and Zr the H2
binds strongly enough for its storage in the so-called Kubas mode, where the H2
bond is sensibly elongated. Other metals (Co, Ni, Ru, Rh and Pd) feature also an
elongated Kubas mode, interesting as well for H2 storage. Sc and Ti display a
Kubas modes especially suited, given their lightness, for meeting the gravimetric
requirements. The H2 interactions with TM adatoms imply a TM -> H2 charge
transfer, although the magnetic moment of the system tends to remain intact,
except for the early 5d TMs, where the unpaired electron transfer seems to be
associated with the H2 bond breakage.
PMID- 29349456
TI - Effects of carotenoids on lipid bilayers.
AB - Carotenoids have been found to be important in improving the integrity of
biomembranes in eukaryotes. However, the molecular details of how carotenoids
modulate the physical properties of biomembranes are unknown. To this end, we
have conducted a series of molecular dynamics simulations of different
biologically-relevant membranes in the presence of carotenoids. The carotenoid
effect on the membrane was found to be specific to the identity of the carotenoid
and the composition of the membrane itself. Therefore, different classes of
carotenoids produce a different effect on the membrane, and different membrane
phases are affected differently by carotenoids. It is apparent from our data that
carotenoids do trigger the bilayer to become thinner. The mechanism by which this
occurs depends on two competing factors, the ability of the lipid tails of
opposing monolayers to either (1) compress or (2) interdigitate as the bilayer
condenses. Indeed, carotenoids directly influence the physical properties via
these two mechanisms, thus compacting the bilayer. However, the degree to which
these competing mechanisms are utilized depends on the bilayer phase and the
carotenoid identity.
PMID- 29349457
TI - Effects of tetrahedral DNA nanostructures on autophagy in chondrocytes.
AB - Tetrahedral DNA nanostructures (TDNs) have gathered great attention and are being
widely used in biomedicine. We demonstrated that autophagy increased after
exposure to TDNs (250 nM) along with the up-regulation of several autophagy
related genes and proteins. TDNs enhanced cell autophagy through the
PI3K/AKT/mTOR signaling pathway.
PMID- 29349458
TI - Trends in adsorption of electrocatalytic water splitting intermediates on cubic
ABO3 oxides.
AB - The reactivity of solid oxide surfaces towards adsorption of oxygen and hydrogen
is a key metric for the design of new catalysts for electrochemical water
splitting. In this paper, we report on trends in the adsorption energy of
different adsorbed intermediates derived from the oxidation and reduction of
water for ternary ABO3 oxides in the cubic perovskite structure. Our findings
support a previously reported trend that rationalizes the observed lower bound in
oxygen evolution (OER) overpotentials from correlations in OH* and OOH*
adsorption energies. In addition, we report hydrogen adsorption energies that may
be used to estimate hydrogen evolution (HER) overpotentials along with potential
metrics for electrochemical metastability in reducing environments. We also
report and discuss trends between atom-projected density of states and adsorption
energies, which may enable a design criteria from the local electronic structure
of the active site.
PMID- 29349459
TI - A versatile single molecular precursor for the synthesis of layered oxide cathode
materials for Li-ion batteries.
AB - A carbonyl-bridged single molecular precursor LiTM(acac)3 [transition metal (TM)
= cobalt/manganese/nickel (Co/Mn/Ni), acac = acetylacetone], featuring a one
dimensional chain structure, was designed and applied to achieve the layered
oxide cathode materials: LiTMO2 (TM = Ni/Mn/Co, NMC). As examples, layered
oxides, primary LiCoO2, binary LiNi0.8Co0.2O2 and ternary LiNi0.5Mn0.3Co0.2O2
were successfully prepared to be used as cathode materials. When they are applied
to lithium-ion batteries (LIBs), all exhibit good electrochemical performance
because of their unique morphology and great uniformity of element distribution.
This versatile precursor is predicted to accommodate many other metal cations,
such as aluminum (Al3+), iron (Fe2+), and sodium (Na+), because of the
flexibility of organic ligand, which not only facilitates the doping-modification
of the NMC system, but also enables synthesis of Na-ion layered oxides. This
opens a new direction of research for the synthesis of high-performance layered
oxide cathode materials for LIBs.
PMID- 29349460
TI - A combined theoretical and experimental investigation on the influence of the
bromine substitution pattern on the photophysics of conjugated organic
chromophores.
AB - A large series of structurally related two-photon photosensitizers with heavy
atom substitution were synthesized and evaluated through a combined spectroscopic
(steady-state and time resolved), photophysical and computational study. Our aim
was to identify some relevant parameters related to their excited state dynamics
including photo-induced singlet oxygen generation. Although these dynamics result
from the interplay of many factors, we show that the triplet excited state
generation kinetics can generally be correlated with the calculated values of
both the spin-orbit coupling and the energy gap between S1 and T1 states, which
themselves mostly depend on the positioning of the heavy atoms along the pi
conjugated structure rather than their number.
PMID- 29349461
TI - Oxygen vacancy rich Cu2O based composite material with nitrogen doped carbon as
matrix for photocatalytic H2 production and organic pollutant removal.
AB - A nitrogen doped carbon matrix supported Cu2O composite material (Cu/Cu2O@NC) was
fabricated successfully with a coordination polymer as precursor through
calcination. In this composite material, Cu2O particles with a size of about 6-10
nm were dispersed evenly in the nitrogen doped carbon matrix. After calcination,
some coordinated nitrogen atoms were doped in the lattice of Cu2O and replace
oxygen atoms, thus generating a large number of oxygen vacancies. In Cu/Cu2O@NC,
the existence of oxygen vacancies has been confirmed by electron spin resonance
(ESR) and X-ray photoelectron spectroscopy (XPS). Under visible light
irradiation, Cu/Cu2O@NC exhibits excellent H2 production with the rate of 379.6
MUmol h-1 g-1. Its photocatalytic activity affects organic dyes, such as
Rhodamine B (RhB) and methyl orange (MO). In addition to photocatalysis,
Cu/Cu2O@NC also exhibits striking catalytic activity in reductive conversion of 4
nitrophenol to 4-aminophenol with in presence of sodium borohydride (NaBH4). The
conversion efficiency reaches almost 100% in 250 s with the quantity of
Cu/Cu2O@NC as low as 5 mg. The outstanding H2 production and organic pollutants
removal are attributed to the oxygen vacancy. We expect that Cu/Cu2O@NC will find
its way as a new resource for hydrogen energy as well as a promising material in
water purification.
PMID- 29349462
TI - Self-assembly of bis-salphen compounds: from semiflexible chains to webs of
nanorings.
AB - The recently-observed self-assembly of certain salphen-based compounds into
neuron-like networks of microrings interconnected with nano-thin strings may
suggest a new highly-potent tool for nanoscale patterning. However, the mechanism
behind such phenomena needs to be clarified before they can be applied in
materials design. Here we show that, in contrast with what was initially
presumed, the emergence of a "rings-and-rods" pattern is unlikely to be explained
by merging, collapse and piercing of vesicles as in previously reported cases of
nanorings self-assembly via non-bonding interactions. We propose an alternative
explanation: the compounds under study form a 1D coordination polymer, the fibres
of which are elastic enough to fold into toroidal globules upon solvent
evaporation, while being able to link separate chains into extended networks.
This becomes possible because the structure of the compound's scaffold is found
to adopt a very different conformation from that inferred in the original work.
Based on ab initio and molecular dynamics calculations we propose a step-by-step
description of self-assembly process of a supramolecular structure which explains
all the observed phenomena in a simple and clear way. The individual roles of the
compound' s scaffold structure, coordination centres, functional groups and
solvent effects are also explained, opening a route to control the morphology of
self-assembled networks and to synthesize new compounds exhibiting similar
behaviour.
PMID- 29349463
TI - Stability and digestibility of one- or bi-layered medium-chain triglyceride
emulsions with gum Arabic and whey protein isolates by pancreatic lipase in
vitro.
AB - Interfacial engineering approaches have been used to design functional foods so
as to control lipase-induced digestion of emulsified lipids and release of
bioactive lipophilic components in the gastrointestinal tract. In this study,
emulsion droplets with the interface stabilized with gum Arabic (GA) and whey
protein isolate (WPI) were prepared by mixing or sequential adsorption. WPI/GA
intramolecular soluble complexes (ISCs) have superior emulsifying properties in
stabilizing oil-in-water emulsions. The impact of the interfaces for WPI/GA ISC
layered (one-layered) and double-layered emulsions formed by sequential
deposition of WPI or GA on the lipolysis of emulsions was investigated using an
in vitro simulated gastrointestinal model. Transglutaminase and dithiothreitol
were introduced to crosslink the interfacial proteins and improve the interfacial
stability. The ISC-layered emulsion was less stable to aggregation than the
double-layered ones in simulated gastric fluid due to dissociation of ISCs caused
by the electrostatic screening of ions and proteolysis of interfacial proteins
driven by pepsin. The ISC-layered emulsion conferred a significant slower rate
and extent of lipid digestion compared to the double-layered emulsions post
gastric proteolysis (P < 0.05). It is presumed for the ISC-layered emulsion that
the destabilization to aggregation and coalescence within the simulated
gastrointestinal fluids and the steric hindrance of the robust and thick
interfacial layer might contribute to delaying free fatty acids release. It
suggests that both the initial interfacial properties and the stability of the
emulsified lipid droplets within the simulated gastrointestinal fluids play an
important role in determining the rate and extent of lipid digestion. It is
predicted that direct destabilization of emulsified lipids using interfacial
engineering approaches has the potential of modifying lipid digestibility or
bioactive release at specific sites within the gastrointestinal tract.
PMID- 29349464
TI - Boundary-induced nucleation control: a theoretical perspective.
AB - The pre-patterning of a substrate to create energetically more attractive or
repulsive regions allows one to generate a variety of structures in physical
vapor deposition experiments. A particularly interesting structure is generated
if the energetically attractive region forms a rectangular grid. For specific
combinations of the particle flux, the substrate temperature and the lattice size
it is possible to generate exactly one cluster per cell, giving rise to
nucleation control. Here, we show that the experimental observations of
nucleation control can be very well understood from a theoretical perspective.
For this purpose we perform, on the one hand, kinetic Monte Carlo simulations
and, on the other hand, use analytical scaling arguments to rationalize the
observed behavior. For several observables, characterizing nucleation control,
very good agreement is found between experiment and theory. This underlines the
generality of the presented mechanism to control the deposition of materials by
manipulation of the direct environment.
PMID- 29349465
TI - Exploring candidate biomarkers for lung and prostate cancers using gene
expression and flux variability analysis.
AB - Genome-scale metabolic models have provided valuable resources for exploring
changes in metabolism under normal and cancer conditions. However, metabolism
itself is strongly linked to gene expression, so integration of gene expression
data into metabolic models might improve the detection of genes involved in the
control of tumor progression. Herein, we considered gene expression data as extra
constraints to enhance the predictive powers of metabolic models. We
reconstructed genome-scale metabolic models for lung and prostate, under normal
and cancer conditions to detect the major genes associated with critical
subsystems during tumor development. Furthermore, we utilized gene expression
data in combination with an information theory-based approach to reconstruct co
expression networks of the human lung and prostate in both cohorts. Our results
revealed 19 genes as candidate biomarkers for lung and prostate cancer cells.
This study also revealed that the development of a complementary approach
(integration of gene expression and metabolic profiles) could lead to proposing
novel biomarkers and suggesting renovated cancer treatment strategies which have
not been possible to detect using either of the methods alone.
PMID- 29349466
TI - Dynamics of networks in a viscoelastic and active environment.
AB - We investigate the dynamics of fractals and other networks in a viscoelastic and
active environment. The viscoelastic dynamics is modeled based on the generalized
Langevin equation, where the activity is introduced to it by means of the
exponentially correlated noise. The intramolecular interactions are taken into
account by the bead-spring picture. The microscopic connectivity (studied in the
form of Vicsek fractals, of dual Sierpinski gaskets, of NTD trees, and of a
family of deterministic small-world networks) reveals itself in the multiscale
monomeric dynamics, which shows vastly different behaviors in the active and
passive baths. In particular, the dynamics under active forces leads to a
swelling that is characterized through power laws which are not present in the
passive case. In all cases, the dynamics reflects the broad scaling behavior of
the density of states and not necessarily the maximal relaxation time of the
structures in a passive bath, as it is exemplified on the NTD trees.
PMID- 29349467
TI - Lysine-derived, pH-sensitive and biodegradable poly(beta-aminoester urethane)
networks and their local drug delivery behaviour.
AB - In this study, a series of covalently crosslinked, l-lysine based poly(beta
aminoester urethane) (LPBAEU) networks with good biodegradability and pH
sensitivity was reported. The effect of hydrophilic/hydrophobic characteristics
and diacrylate/amine molar ratio on the structure, swelling and degradation
behaviour of the networks was investigated. The water transport mechanism and
dynamic swelling behavior of the LPBAEU networks were strongly affected by medium
pH, and swelling amounts up to 252.2% and 148.7% were observed at pH 5.6 and pH
7.4, respectively. It was found that water diffusion within the networks followed
a non-Fickian mechanism. The LPBAEU network with the highest diacrylate/amine
molar ratio exhibited the highest tensile strength and Young's modulus. In vitro
mass losses of networks showed that the degradation rate of LPBAEU networks can
be adjusted from 4 to 14 days. LPBAEU networks also supported loading of
doxycycline hyclate (DH) and in vitro release studies demonstrated that release
of DH from the networks was substantially hindered in the neutral pH environment,
with 20.9-56.2% DH release, whereas DH release was accelerated under mild acidic
conditions, with a release percentage of 36.6-99.6%. The release data were fitted
to different mathematical models and the obtained results confirmed that these
networks released DH in a non-Fickian mechanism. The results of this research
support the idea that pH-responsive LPBAEU networks may find potential
applications in local drug delivery.
PMID- 29349468
TI - Absolute and relative-rate measurement of the rate coefficient for reaction of
perfluoro ethyl vinyl ether (C2F5OCF[double bond, length as m-dash]CF2) with OH.
AB - The rate coefficient (k1) for the reaction of OH radicals with perfluoro ethyl
vinyl ether (PEVE, C2F5OCF[double bond, length as m-dash]CF2) has been measured
as a function of temperature (T = 207-300 K) using the technique of pulsed laser
photolysis with detection of OH by laser-induced fluorescence (PLP-LIF) at
pressures of 50 or 100 Torr N2 bath gas. In addition, the rate coefficient was
measured at 298 K and in one atmosphere of air by the relative-rate technique
with loss of PEVE and reference reactant monitored in situ by IR absorption
spectroscopy. The rate coefficient has a negative temperature dependence which
can be parameterized as: k1(T) = 6.0 * 10-13 exp[(480 +/- 38/T)] cm3 molecule-1 s
1 and a room temperature value of k1 (298 K) = (3.0 +/- 0.3) * 10-12 cm3 molecule
1 s-1. Highly accurate rate coefficients from the PLP-LIF experiments were
achieved by optical on-line measurements of PEVE and by performing the
measurements at two different apparatuses. The large rate coefficient and the
temperature dependence indicate that the reaction proceeds via OH addition to the
C[double bond, length as m-dash]C double bond, the high pressure limit already
being reached at 50 Torr N2. Based on the rate coefficient and average OH levels,
the atmospheric lifetime of PEVE was estimated to be a few days.
PMID- 29349469
TI - Dopant-dependent crystallization and photothermal effect of Sb-doped SnO2
nanoparticles as stable theranostic nanoagents for tumor ablation.
AB - Ideal theranostic nanoagents should be "all-in-one" type nanocrystals that have a
single-semiconductor component and all-required properties (such as imaging and
photothermal effects), but most semiconductor nanocrystals do not have these
required properties. With SnO2 as a model of a typical wide-band semiconductor,
we report the tuning from UV-responsive SnO2 to blue SnO2 nanocrystals with
imaging ability and a Sb-doping-dependent photothermal effect. Sb-Doped SnO2
nanocrystals were prepared by heating SbCl3 and SnCl4 in benzyl alcohol solution
through a facile solvothermal route. When the SbCl3/SnCl4 molar ratio increases
from 0 to 0.2/1, the obtained samples exhibit an increased photothermal effect
under the irradiation of a 1064 nm laser, accompanied by gradually decreased size
and crystallinity. With a further increase of the molar ratio from 0.3/1.0 to
1.0/1.0, the resulting samples demonstrate the tetragonal SnO2 phase with
amorphous-like compounds and they show no obvious enhancement of a photothermal
effect. After a surface modification with biological molecules, the optimized
Sb0.2-SnO2 nanocrystals demonstrated good stability and a high photothermal
conversion efficiency of 48.3% as well as low cytotoxicity. When Sb0.2-SnO2 was
injected into a tumor of mice, the tumor could be simultaneously detected by X
ray computed tomography (CT) and photoacoustic (PA) imaging, and then thermally
ablated when exposed to a 1064 nm laser. Therefore, these nanocrystals can be
used as "all-in-one" type nanoagents for imaging guided photothermal ablation of
tumors under the irradiation of a laser in the second bio-transparent window.
PMID- 29349475
TI - Continuous splitting of aqueous droplets at the interface of co-flowing
immiscible oil streams in a microchannel.
AB - We report the continuous splitting of aqueous droplets at the interface between
two co-flowing immiscible oil streams in a microchannel. The aqueous droplets
initially present in a primary continuous stream (CP1) migrate into a secondary
continuous stream (CP2) when the ratio of the non-inertial lift force to the
interfacial tension force exceeds a critical value (K. S. Jayaprakash, U.
Banerjee and A. K. Sen, Langmuir, 2016, 32, 2136-2143). Here, experiments were
performed to understand the droplet splitting phenomenon and demonstrate the
splitting of droplets encapsulating microbeads and cells. The results showed that
the droplet splitting phenomenon is governed by the capillary number Ca, which is
a function of the average shear stress across the channel, interfacial tension
sigma between the CP1 and the droplet phase and the droplet length-scale L.
Irrespective of the individual values of these parameters, droplet splitting was
observed when the capillary number Ca exceeds a critical value Cacr, which was
found to be a function of droplet to CP2 viscosity ratio lambda. The Cacr was
found to be minimum for lambda ~ 1 but higher for droplets of lambda ? 1 and
lambda ? 1. The sizes of the primary and secondary daughter and migrated droplets
(i.e. Lp|sD and Lp|sM) were found to increase linearly with the increase in the
size of the primary or secondary parent droplets (Lp|sP). Splitting of parent
droplets encapsulating a single microbead or PBMC showed that after splitting,
the presence of the microbead or PBMC in the daughter or migrated droplets
depends on the ratio of the size of the migrated droplets to that of the parent
droplet (i.e. VM/VP). Finally, splitting of parent droplets containing two or
more microbeads or cells into droplets containing a single particle or cell was
demonstrated. A new paradigm of droplet splitting is reported that could find
applications in soft matter and single-cell studies.
PMID- 29349476
TI - Monitoring the formation of PtNi nanoalloys supported on hollow graphitic spheres
using in situ pair distribution function analysis.
AB - This article aims to address the formation and the structural
disordering/ordering phenomena of PtNi nanoalloys supported on hollow graphitic
spheres (HGSs) using pair distribution function (PDF) analysis under ex situ/in
situ data collection conditions. Starting from small nanoparticles (10-15 A in
diameter) embedded in HGSs, structural changes were monitored during stepwise
heating and cooling of the sample using in situ PDF analysis. In order to
evaluate the conventional synthesis route for the production of PtNi nanoalloys
supported on HGSs, ex situ PDF experiments were performed before and after heat
treatment in a furnace. The studies demonstrate that the local structure of the
in situ synthesised PtNi nanoalloy differs from its ex situ synthesised
counterpart. A partially ordered PtNi nanoalloy was obtained during the stepwise
in situ cooling of the precursor, whereas the conventional ex situ synthesis
route did not lead to the formation of an ordered crystal structure. In this
study we could show that rapid heating and cooling results in a disordered PtNi
alloy whereas slow heating and cooling leads to disorder-order transitions in
PtNi.
PMID- 29349477
TI - Isomerism and reactivity of nickel(ii) acetylacetonate bis(thiosemicarbazone)
complexes.
AB - The complexation of nickel(ii) with acetylacetonate bis(thiosemicarbazone) N2S2
ligands with varying substituents has revealed that two isomers can exist
independently in solution. These isomers differ according to the formation of
either a 5,6,5-membered (symmetric) or a 4,7,5-membered (asymmetric) chelate ring
arrangement. These two isomers have distinctly different properties. The
symmetric complex (sym-[Ni(acacR)]) is unstable in the presence of air and slowly
converts to the oxidised analogue sym-[Ni(acacRO)] with a carbonyl group
installed at the apical C-atom. The mechanism of this O-atom transfer reaction is
still unclear but kinetic and spectroelectrochemical experiments in addition to
Density Functional Theory calculations have identified a single electron oxidised
NiII-ligand radical complex as a key intermediate. By contrast the asymmetric
complex, asym-[Ni(acacR)] is inert to ligand oxidation.
PMID- 29349478
TI - Affinity to host population stimulates physical growth in adult offspring of
Turkish migrants in Germany.
AB - ABSTRACT: Because of political conflicts and climate change, migration will be
increased worldwide and integration in host societies is a challenge also for
migrants. We hypothesize that migrants, who take up the challenge in a new social
environment are taller than migrants who do not pose this challenge. We analyze
by a questionnaire possible social, nutritional and ethnic influencing factors to
body height (BH) of adult offspring of Turkish migrants (n = 82, 39 males) aged
from 18 to 34 years (mean age 24.6 years). The results of multiple regression
(downward selection) show that the more a male adult offspring of Turkish
migrants feels like belonging to the Turkish culture, the smaller he is (95% CI,
3.79, -0.323). Further, the more a male adult offspring of Turkish migrants feels
like belonging to the German culture, the taller he is (95% CI, -0.152, 1.738).
We discussed it comparable to primates taking up their challenge in dominance,
where as a result their body size increase is associated with higher IGF-1 level.
IGF-1 is associated with emotional belonging and has a fundamental role in the
regulation of metabolism and growth of the human body. With all pilot
characteristics of our study results show that the successful challenge of
integration in a new society is strongly associated with the emotional
integration and identification in the sense of a personal sense of belonging to
society. We discuss taller BH as a signal of social growth adjustment. In this
sense, a secular trend of BH adaptation of migrants to hosts is a sign of
integration.
PMID- 29349479
TI - Resilience and protective factors among people with a history of child
maltreatment: a systematic review.
AB - PURPOSE: To provide an overview of resilience and protective factors associated
with a better life following child maltreatment exposure, to compare protective
factors across specific subtypes of maltreatment, and to explore existing issues
in the current state of the literature. METHODS: Electronic databases and grey
literature up to October 2017 were systematically searched for English language
with observational study designs for the research on resilience and childhood
maltreatment. Systematic review and qualitative approaches were used to
synthesize the results. Study quality and heterogeneity were also examined.
RESULTS: Initial screening of titles and abstracts resulted in 247 papers being
reviewed. A total of 85 articles met eligibility criteria of this review. Most of
these studies had low or middle study quality. There were two subgroups of
studies reviewed: (1) 11 studies examined whether resilience protected against
the negative consequence of childhood maltreatment, and, (2) 75 studies explored
what protective factor was associated with a kind of adaptive functioning.
Although the conceptualization of resilience significantly varied from study to
study, protective factors associated with resilience at individual, familial, and
societal levels reduced the likelihood of negative consequences of childhood
maltreatment. Negative consequences following childhood maltreatment can be
prevented or moderated if protective factors are provided in time. Future
research needs to address the conceptualization issue of resilience. CONCLUSIONS:
Public and population mental health preventions should focus on early childhood
and apply preventive strategies as early as possible. Cost-effective studies
should be considered in the evaluation of resilience prevention program.
PMID- 29349480
TI - Posture modulates the sensitivity of the H-reflex.
AB - The effect of body posture on the human soleus H-reflex via electrical
stimulation of the tibial nerve at the popliteal fossa was studied. All
parameters that may influence the reflex were controlled stringently. H-reflexes
were elicited in three different body postures while keeping the level of
background muscle activation to a minimum. The H-reflex curve relative to the M
wave curve did not change significantly in any of the body postures. However, the
maximal H-reflex amplitude significantly increased in the prone position compared
with the sitting (p = 0.02) and standing positions (p = 0.01). The background
level of electrical activity of the soleus muscle did not significantly change
during varying body postures. Together, these findings indicate that the
effectiveness of the spindle primary afferent synapse on the soleus motor neuron
pool changes significantly in prone position as compared to sitting and standing
positions. Given that we have controlled the confounding factors excluding the
head position relative to the gravity and the receptors that may be
differentially activated at varying body postures such as the proprioceptors, it
is concluded that the tonic activity from these receptors may presynaptically
interfere with the effectiveness of the spindle primary afferent synapses on the
soleus motor neurons.
PMID- 29349481
TI - Systematic review and comparison of national and international guidelines on
diverticular disease.
AB - PURPOSE: Diverticular disease is common and of increasing medical and economical
importance. Various practice guidelines on diagnostic and treatment on this
disease exist. We compared current guidelines on the disease in order to identify
concordant and discordant recommendations. METHOD: Eleven national and
international guidelines on diverticular disease published over the last 10 years
have been identified by a systematic literature review on PubMed and compared in
detail for 20 main and 51 subtopics. RESULTS: The available evidence for the most
aspects was rated as moderate or low. There was concordance for the following
items: Diagnosis of diverticulitis should be confirmed by imaging methods (10 of
10 guidelines). Mild forms may be treated out-patient (10/10). Abscesses are
treated non-surgically (9/9). Elective surgery should be indicated by individual
patient-related factors, only, and be performed laparoscopically (10/10, 9/9
respectively). Main differences were found in the questions of appropriate
classification, imaging diagnostic (computed-tomography versus ultra-sound), need
for antibiotics in out-patient treatment and mode of surgery for diverticular
perforation. Despite growing evidence that antibiotics are not needed for
treating mild diverticulitis, only 3/10 guidelines have corresponding
recommendations. Hartmann's procedure has been abandoned several years ago and is
now recommended for feculent peritonitis by the three most recent guidelines. In
contrast, laparoscopic lavage without resection is not recommended anymore.
CONCLUSION: There are dissents in the recommendations for central aspects
regarding the diagnostic and treatment of diverticular disease in recently
published guidelines.
PMID- 29349482
TI - [Esophageal diverticula (excluding cricopharyngeal diverticula)].
AB - Diverticula of the middle and lower third of the esophagus are commonly
associated with esophageal motility disorders. The increase of intraluminal
pressure leads to an outpouching of the mucosal and submucosal layers through the
esophageal muscle coat. These pouches are also called false diverticula, because
they only consist of the mucosal and submucosal esophageal layers. In contrast,
the more rarely encountered true diverticula that retain the complete esophageal
wall are generally associated with periesophageal granulomatous lymph node
disease. Treatment of both true and false diverticula is generally indicated in
symptomatic patients; however, even state of the art minimally invasive surgery
is accompanied by considerable perioperative morbidity and should only be
performed in carefully selected patients. This aim of this article is to
summarize the available scientific evidence and to provide the reader with an
updated guide to best clinical practice in the treatment of esophageal
diverticula.
PMID- 29349483
TI - Surgical Outcomes of Primary Versus Post-Neoadjuvant Chemotherapy Breast
Conservation Surgery: A Comparative Study from a Developing Country.
AB - INTRODUCTION: In India and other developing countries, breast conservation
surgery (BCS) rates in breast cancer patients are low due to advanced disease at
presentation and misconceptions about BCS outcomes. Many patients presenting with
large or locally advanced breast cancers (LABC) can be offered post-neoadjuvant
chemotherapy (NACT) BCS, safety of which is not as well established as that of
primary BCS. This retrospective study compared pathological and surgical outcome
parameters in patients undergoing primary and post-NACT BCS. METHODS: All non
metastatic breast cancer patients undergoing BCS during 2011-2015 with 1-year
follow-up were included. Outcome parameters in form of margin infiltration,
ipsilateral breast tumor recurrence (IBTR) rates and IBTR-free survival were
compared between primary and post-NACT BCS patients groups. RESULTS: One hundred
and twenty-nine patients underwent BCS; 95 underwent primary and 34 post-NACT
BCS. Patients in both groups underwent similar multimodality treatment as per
institutional protocols. Post-NACT patients more frequently required oncoplastic
volume displacement or replacement surgery (p = 0.002). Re-excision of
infiltrated margins was needed more frequently in primary BCS compared with post
NACT BCS group (14.4 vs. 8.8%; p = 0.40). IBTR (Mean follow-up = 30.7 months) was
seen in 8.8% post-NACT patients compared with 2.1% primary BCS (p = 0.114). IBTR
free survival did not differ significantly between the groups in stage-wise
comparison. CONCLUSION: Post-NACT BCS is safe even in large tumors and LABC,
though many require oncoplastic procedures for satisfactory cosmesis. In a
developing country where many patients present with large breast cancers or LABC,
the benefits of BCS can be offered to a majority with the help of NACT, without
compromising the chances of cure.
PMID- 29349484
TI - Overall Survival of Papillary Thyroid Carcinoma Patients: A Single-Institution
Long-Term Follow-Up of 5897 Patients.
AB - INTRODUCTION: Papillary thyroid carcinoma (PTC) generally shows an excellent
prognosis except in cases with aggressive backgrounds or clinicopathological
features. Although the cause-specific survival (CSS) of PTC patients has been
extensively investigated, the overall survival (OS) of these patients is unclear.
We herein investigated both the OS and CSS of a large PTC patient series.
MATERIALS AND METHODS: We enrolled 5897 PTC patients who underwent initial
surgery between 1987 and 2005 (658 males and 5339 females; median age 51 years).
Their median postoperative follow-up period was 177 months. Univariate and
multivariate analyses for OS and CSS assessed the effects of gender, older age
(>=55 years), distant metastasis at diagnosis (M1), significant extrathyroid
extension, tumor size (cutoffs 2 and 4 cm), large node metastasis (N >= 3 cm),
and extranodal tumor extension. RESULTS: To date, 387 patients (7%) in this
series have died from various causes, including 117 (2%) due to PTC. The 10-, 15
, and 20-year OS rates are 97, 95, and 90%, respectively. Older age and M1 were
important prognostic factors for OS and CSS. Older age was a more significant
factor than M1 for OS and vice versa for CSS. In the older patients, M1 was a
prominent prognostic factor for both OS and CSS. In the young patients, M1 had
less prognostic impact than in the older patients, and the prognostic values of
M1 and N >= 3 cm for OS and CSS were identical and similar, respectively.
CONCLUSIONS: The most important prognostic value for OS was patient age,
indicating that PTC is generally indolent. However, the control of distant
metastasis in older patients remains a future challenge in order to further
improve their OS and CSS. PTC of >=3 cm in young patients should be carefully
followed, even in the absence of metastases, and these patients should undergo
aggressive therapies for recurrent lesions and metastases.
PMID- 29349485
TI - Undiagnosed Primary Hyperparathyroidism and Recurrent Miscarriage: The First
Prospective Pilot Study.
AB - BACKGROUND: Primary hyperparathyroidism (pHPT) in pregnancy is reported to be
associated with significant maternal and foetal complications and an up to
threefold increase in the risk of miscarriage. However, the true incidence of
pHPT in pregnancy, complete and miscarried, is unknown and there are no data on
the prevalence of undiagnosed pHPT in recurrent miscarriage (RM) (>=3 consecutive
miscarriages under 24-week gestation). This is the first prospective study aiming
to establish the prevalence of undiagnosed pHPT in RM. METHODS: Following UK
National ethics committee approval, women who had experienced 3 or more
consecutive miscarriages were recruited from a nationwide RM clinic. Serum
corrected calcium, phosphate, PTH and vitamin D were evaluated. Patients with
raised serum calcium and/or PTH were recalled for confirmatory tests. Power
calculations suggested that a minimum of 272 patients were required to
demonstrate a clinically significant incidence of pHPT. RESULTS: Three hundred
women were recruited, median age 35 years (range 19-42). Eleven patients had
incomplete data, leaving 289 patients suitable for analysis; 50/289 patients
(17%) with abnormal tests were recalled. The prevalence of vitamin D deficiency
(<25 nmol/l) and insufficiency (25-75 nmol/l) was 8.7 and 67.8%, respectively.
One patient was diagnosed with pHPT (0.34%) and underwent successful
parathyroidectomy. CONCLUSIONS: The prevalence of undiagnosed pHPT (0.34%) in RM
in this study appears to be many times greater than the 0.05% expected in this
age group. The findings of this pilot study merit follow-up with a larger-scale
study. Routine serum calcium estimation is not currently undertaken in RM and
should be considered.
PMID- 29349486
TI - Hydatid Cyst of the Liver: A Challenge that can be Amplified Shifting from Open
to Laparoscopic Surgery.
PMID- 29349487
TI - Lay First Responder Training in Eastern Uganda: Leveraging Transportation
Infrastructure to Build an Effective Prehospital Emergency Care Training Program.
AB - BACKGROUND: Though road traffic injuries (RTIs) are a major cause of mortality in
East Africa, few countries have emergency medical services. The aim was to create
a sustainable and efficient prehospital lay first responder program, creating a
system with lay first responders spread through the 53 motorcycle taxi stages of
Iganga Municipality. METHODS: One hundred and fifty-four motorcycle taxi riders
were taught a first aid curriculum in partnership with a local Red Cross first
aid trainer and provided with a first aid kit following WHO guidelines for basic
first aid. Pre- and post-survey tests measured first aid knowledge improvement
over the course. Post-implementation incident report forms were collected from
lay first responders after each patient encounter over 6 months. Follow-up
interviews were conducted with 110 of 154 trainees, 9 months post-training.
RESULTS: Improvement was measured across all five major first aid categories:
bleeding control (56.9 vs. 79.7%), scene management (37.6 vs. 59.5%), airway and
breathing (43.4 vs. 51.6%), recovery position (13.1 vs. 43.4%), and victim
transport (88.2 vs. 94.3%). From the incident report findings, first responders
treated 250 victims (82.8% RTI related) and encountered 24 deaths (9.6% of
victims). Of the first aid skills, bleeding control and bandaging was used most
often (55.2% of encounters). Lay first responders provided transport in 48.3% of
encounters. Of 110 lay first responders surveyed, 70 of 76 who had used at least
one skill felt "confident" in the care they provided. CONCLUSION: A prehospital
care system composed of lay first responders can be developed leveraging existing
transport organizations, offering a scalable alternative for LMICs, demonstrating
usefulness in practice and measurable educational improvements in trauma skills
for non-clinical lay responders.
PMID- 29349488
TI - One-step synthesis of an 18F-labeled boron-derived methionine analog: a
substitute for 11C-methionine?
AB - Amino acid-based tracers have been extensively investigated for positron emission
tomography (PET) imaging of brain tumors, and 11C-methionine (11C-MET) is one of
the most extensively investigated. However, widespread clinical use of 11C-MET is
challenging due to the short half-life of 11C and low radiolabeling yield. In
this issue of the European Journal of Nuclear Medicine and Molecular Imaging,
Yang and colleagues report an 18F-labeled boron-derived methionine analog, 18F-B
MET, as a potential substitute for 11C-MET in PET imaging of glioma. The push
button synthesis, highly efficient radiolabeling, and good imaging performance in
glioma models make this tracer a promising candidate for future clinical
translation.
PMID- 29349489
TI - Characterization of multiple antilisterial peptides produced by sakacin P
producing Lactobacillus sakei subsp. sakei 2a.
AB - Antimicrobial compounds produced by lactic acid bacteria can be explored as
natural food biopreservatives. In a previous report, the main antimicrobial
compounds produced by the Brazilian meat isolate Lactobacillus sakei subsp. sakei
2a, i.e., bacteriocin sakacin P and two ribosomal peptides (P2 and P3) active
against Listeria monocytogenes, were described. In this study, we report the
spectrum of activity, molecular mass, structural identity and mechanism of action
of additional six antilisterial peptides produced by Lb. sakei 2a, detected in a
24 h-culture in MRS broth submitted to acid treatment (pH 1.5) and proper
fractionation and purification steps for obtention of free and cell-bound
proteins. The six peptides presented similarity to different ribosomal proteins
of Lb. sakei subsp sakei 23K and the molecular masses varied from 4.6 to 11.0
kDa. All peptides were capable to increase the efflux of ATP and decrease the
membrane potential in Listeria monocytogenes. The activity of a pool of the
obtained antilisterial compounds [enriched active fraction (EAF)] against
Listeria monocytogenes in a food model (meat gravy) during refrigerated storage
(4 degrees C) for 10 days was also tested and results indicated that the
populations of L. monocytogenes in the food model containing the acid extract
remained lower than those at time 0-day, evidencing that the acid extract of a
culture of Lb. sakei 2a is a good technological alternative for the control of
growth of L. monocytogenes in foods.
PMID- 29349490
TI - Auto-aggregation properties of a novel aerobic denitrifier Enterobacter sp.
strain FL.
AB - Enterobacter sp. strain FL was newly isolated from activated sludge and exhibited
significant capability of auto-aggregation as well as aerobic denitrification.
The removal efficiencies of NO3--N, total nitrogen (TN), and TOC by strain FL in
batch culture reached 94.6, 63.9, and 72.5% in 24 h, respectively. The production
of N2O and N2 in the presence of oxygen demonstrated the occurrence of aerobic
denitrification. The auto-aggregation index of strain FL reached 54.3%,
suggesting a high tendency that the cells would agglomerate into aggregates. The
production of extracellular polymeric substances (EPSs), which were mainly
composed of proteins followed by polysaccharides, was considered to be related to
the cell aggregation according to Fourier transform infrared (FT-IR) and confocal
laser scanning microscopy (CLSM). The proteins in EPS were evenly and tightly
combined to cells and altered the protein secondary structures of cell surface
from random coils to beta-sheets and three-turn helices. The alteration of
protein secondary structures of cell surface caused by the proteins in EPS might
play a dominant role in the auto-aggregation of strain FL. To further assess the
feasibility of strain FL for synthetic wastewater treatment, a sequencing batch
reactor (SBR), solely inoculated with strain FL, was conducted. During the 16
running cycles, the removal efficiency of NO3--N was 90.2-99.7% and the auto
aggregation index was stabilized at 35.0-41.5%. The EPS promoted the biomass of
strain FL to aggregate in the SBR.
PMID- 29349491
TI - Formulation and stabilization of an Arthrobacter strain with good storage
stability and 4-chlorophenol-degradation activity for bioremediation.
AB - Chlorophenols are widespread and of environmental concern due to their toxic and
carcinogenic properties. Development of less costly and less technically
challenging remediation methods are needed; therefore, we developed a formulation
based on micronized vermiculite that, when air-dried, resulted in a granular
product containing the 4-chlorophenol (4-CP)-degrading Gram-positive bacterium
Arthrobacter chlorophenolicus A6. This formulation and stabilization method
yielded survival rates of about 60% that remained stable in storage for at least
3 months at 4 degrees C. The 4-CP degradation by the formulated and desiccated
A. chlorophenolicus A6 cells was compared to that of freshly grown cells in
controlled-environment soil microcosms. The stabilized cells degraded 4-CP
equally efficient as freshly grown cells in two different set-ups using both
hygienized and non-treated soils. The desiccated microbial product was
successfully employed in an outdoor pot trial showing its effectiveness under
more realistic environmental conditions. No significant phytoremediation effects
on 4-CP degradation were observed in the outdoor pot experiment. The 4-CP
degradation kinetics from both the microcosms and the outdoor pot trial were used
to generate a predictive model of 4-CP biodegradation potentially useful for
larger-scale operations, enabling better bioremediation set-ups and saving of
resources. This study also opens up the possibility of formulating and
stabilizing also other Arthrobacter strains possessing different desirable
pollutant-degrading capabilities.
PMID- 29349492
TI - Ganoderma lucidum phosphoglucomutase is required for hyphal growth,
polysaccharide production, and cell wall integrity.
AB - Phosphoglucomutase (pgm) is an important enzyme in carbohydrate metabolism that
is located at the branching point between glycolysis and the Leloir pathway. pgm
catalyzes the reversible conversion reaction between glucose-6-phosphate (Glc-6
P) and glucose-1-phosphate (Glc-1-P). The glpgm gene was cloned in Escherichia
coli, and the recombinant pgm protein from Ganoderma lucidum was purified in this
study. The activity of native pgm was also detected to demonstrate that this
predicted gene was functional in G. lucidum. Interestingly, silencing the glpgm
gene in the fungus reduced hyphal growth. Moreover, glpgm silencing was
associated with declining extracellular polysaccharide (EPS) production
(approximately 20-40% of that in the WT strain) and increasing intracellular
polysaccharide (IPS) production (approximately 1.7-fold that in the WT strain).
Additionally, in our research, cell wall components were also shown to differ
according to the glpgmi strain. Compared with WT, chitin significantly increased
by 1.5-fold; however, the content of beta-1,3-glucan was observably reduced to 60
70% that of the WT. Further research showed that the cell wall component changes
were associated with the transcription of related genes. These findings provide
references for further study on the potential physiological function of pgm in G.
lucidum.
PMID- 29349493
TI - Biotic elicitation of ginsenoside metabolism of mutant adventitious root culture
in Panax ginseng.
AB - Biotic elicitation is an important biotechnological strategy for triggering the
accumulation of secondary metabolites in adventitious root cultures. These biotic
elicitors can be obtained from safe, economically important strains of bacteria
found in the rhizosphere and fermented foods. Here, we assayed the effects of
filtered cultures of five nitrogen-fixing bacteria and four types of fermentation
bacteria on mutant adventitious Panax ginseng root cultures induced in a previous
study by colchicine treatment. The biomass, pH, and electrical conductivity (EC)
of the culture medium were altered at 5 days after treatment with bacteria. The
saponin content was highest in root cultures treated with Mesorhizobium amorphae
(GS3037), with a concentration of 105.58 mg g-1 dry weight saponin present in
these cultures versus 74.48 mg g-1 dry weight in untreated root cultures. The
accumulation of the ginsenosides Rb2 and Rb3 dramatically increased (19.4- and
4.4-fold, and 18.8- and 4.8-fold) 5 days after treatment with M. amorphae
(GS3037) and Mesorhizobium amorphae (GS336), respectively. Compound K production
increased 1.7-fold after treatment with M. amorphae (GS3037) compared with
untreated root cultures. These results suggest that treating mutant adventitious
root cultures with biotic elicitors represents an effective strategy for
increasing ginsenoside production in Panax ginseng.
PMID- 29349494
TI - Light scattering on PHA granules protects bacterial cells against the harmful
effects of UV radiation.
AB - Numerous prokaryotes accumulate polyhydroxyalkanoates (PHA) in the form of
intracellular granules. The primary function of PHA is the storage of carbon and
energy. Nevertheless, there are numerous reports that the presence of PHA
granules in microbial cells enhances their stress resistance and fitness when
exposed to various stress factors. In this work, we studied the protective
mechanism of PHA granules against UV irradiation employing Cupriavidus necator as
a model bacterial strain. The PHA-accumulating wild type strain showed
substantially higher UV radiation resistance than the PHA non-accumulating
mutant. Furthermore, the differences in UV-Vis radiation interactions with both
cell types were studied using various spectroscopic approaches (turbidimetry,
absorption spectroscopy, and nephelometry). Our results clearly demonstrate that
intracellular PHA granules efficiently scatter UV radiation, which provides a
substantial UV-protective effect for bacterial cells and, moreover, decreases the
intracellular level of reactive oxygen species in UV-challenged cells. The
protective properties of the PHA granules are enhanced by the fact that granules
specifically bind to DNA, which in turn provides shield-like protection of DNA as
the most UV-sensitive molecule. To conclude, the UV-protective action of PHA
granules adds considerable value to their primary storage function, which can be
beneficial in numerous environments.
PMID- 29349495
TI - Genomic-driven discovery of an amidinohydrolase involved in the biosynthesis of
mediomycin A.
AB - Clethramycin (1) and mediomycin A (2) belong to the linear polyene polyketide
(LPP) family of antibiotics that exhibit potent antifungal activity. Structural
similarities exist between 1 and 2, except that 2 contains an amino moiety
substituted for the guanidino moiety. Herein, the draft genome sequence of
Streptomyces mediocidicus ATCC23936, a strain which produces both 1 and 2, was
obtained through de novo sequencing. Bioinformatic analysis of the genome
revealed a clethramycin (cle) gene cluster that contained 25 open reading frames
(orfs). However, amidinohydrolase for 2 formation was not found in the cle gene
cluster. Further genomic analysis revealed an amidinohydrolase MedX, which can
hydrolyse the guanidino form (1) into the amino form (2) via heterologous co
expression of the cle cluster in Streptomyces lividans or by in vitro catalysis.
These results also suggest the feasibility of engineering novel LPPs for drug
discovery by manipulating the biosynthetic machinery of S. mediocidicus.
PMID- 29349498
TI - Plasma metabolites associated with type 2 diabetes in a Swedish population: a
case-control study nested in a prospective cohort.
AB - AIMS/HYPOTHESIS: The aims of the present work were to identify plasma metabolites
that predict future type 2 diabetes, to investigate the changes in identified
metabolites among individuals who later did or did not develop type 2 diabetes
over time, and to assess the extent to which inclusion of predictive metabolites
could improve risk prediction. METHODS: We established a nested case-control
study within the Swedish prospective population-based Vasterbotten Intervention
Programme cohort. Using untargeted liquid chromatography-MS metabolomics, we
analysed plasma samples from 503 case-control pairs at baseline (a median time of
7 years prior to diagnosis) and samples from a subset of 187 case-control pairs
at 10 years of follow-up. Discriminative metabolites between cases and controls
at baseline were optimally selected using a multivariate data analysis pipeline
adapted for large-scale metabolomics. Conditional logistic regression was used to
assess associations between discriminative metabolites and future type 2
diabetes, adjusting for several known risk factors. Reproducibility of identified
metabolites was estimated by intra-class correlation over the 10 year period
among the subset of healthy participants; their systematic changes over time in
relation to diagnosis among those who developed type 2 diabetes were investigated
using mixed models. Risk prediction performance of models made from different
predictors was evaluated using area under the receiver operating characteristic
curve, discrimination improvement index and net reclassification index. RESULTS:
We identified 46 predictive plasma metabolites of type 2 diabetes. Among novel
findings, phosphatidylcholines (PCs) containing odd-chain fatty acids (C19:1 and
C17:0) and 2-hydroxyethanesulfonate were associated with the likelihood of
developing type 2 diabetes; we also confirmed previously identified predictive
biomarkers. Identified metabolites strongly correlated with insulin resistance
and/or beta cell dysfunction. Of 46 identified metabolites, 26 showed
intermediate to high reproducibility among healthy individuals. Moreover, PCs
with odd-chain fatty acids, branched-chain amino acids, 3-methyl-2-oxovaleric
acid and glutamate changed over time along with disease progression among
diabetes cases. Importantly, we found that a combination of five of the most
robustly predictive metabolites significantly improved risk prediction if added
to models with an a priori defined set of traditional risk factors, but only a
marginal improvement was achieved when using models based on optimally selected
traditional risk factors. CONCLUSIONS/INTERPRETATION: Predictive metabolites may
improve understanding of the pathophysiology of type 2 diabetes and reflect
disease progression, but they provide limited incremental value in risk
prediction beyond optimal use of traditional risk factors.
PMID- 29349499
TI - Spatial coverage of mangrove communities in the Arabian Gulf.
AB - Mangroves are the natural protectors of the coast, carbon sinks, and a nursery to
many terrestrial as well as aquatic organisms. Different effects caused by
natural forces together with anthropogenic factors have reduced mangrove cover on
a global scale, yet little is known about the overall surface covered by
mangroves in the Arabian Gulf. Therefore, the aim of this study was to examine
their spatial coverage and distribution along the Gulf coastlines, using 25
satellite imagery recently acquired from Landsat 8 data for the year 2017. This
study found about 165 km2 of fragmented scattered mangroves, mostly intense in
the United Arab Emirates, where plantation projects have likely played a
significant role in increasing their cover over the years. Whereas mangrove in
Kuwait is rare, areas like Bahrain, Qatar and Saudi Arabia remained stable with a
slight increase. However, mangroves in Iran appear to suffer a decline throughout
the years.
PMID- 29349502
TI - A biomechanical comparison of different fixation techniques for fractures of the
acetabular posterior wall.
AB - PURPOSE: This study aimed to evaluate the biomechanical stability of different
fixation techniques for fractures of the acetabular posterior wall. The
hypothesis was that a reconstruction plate, combined with compression screw
fixation and a plate placed lateral to the screws, would achieve a higher peak
load to failure and stiffness and reduced gapping during cycle loading than other
fixation techniques. METHODS: A total of 24 Sawbone pelvis models were created
with simulated fractures at the posterior wall of the acetabulum. Anatomic
reduction and internal fixation were performed randomly using one of four
techniques: (A) reconstruction plate and compression screw fixation was placed
with a plate medial to the screws; (B) plate and screw fixation with the plate
located lateral to the screws; (C) plate fixation alone, and (D) screw fixation
alone. Six models were tested in each group under cyclic and sustaining loading
tests. Peak load to failure and stiffness were calculated from load displacement
curves. RESULTS: Peak load to failure and stiffness in group B (3698.71 N and
2900.48 N/mm, respectively), featuring reconstruction plate and compression screw
fixation with the plate placed lateral to the screws, were significantly higher
than groups C (2508.74 N, 1602.75 N/mm) and D (2332.06 N, 1454.26 N/mm). No
statistical differences were observed when group A (2941.60 N, 2136.50 N/mm) was
compared with the other groups. There were no significant differences in gapping
between groups. CONCLUSIONS: Fixation using a reconstruction plate and
compression screws placed lateral to the screws may address acetabular posterior
wall fractures in a more appropriate manner than techniques using only plates or
screws. However, this study does not provide evidence to support the fact that
placing the plate lateral to the screws is advantageous in comparison with other
techniques.
PMID- 29349500
TI - Exogenous H2S switches cardiac energy substrate metabolism by regulating SIRT3
expression in db/db mice.
AB - : Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as
anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive
oxygen species production. Sirtuin 3 (SIRT3) is a NAD + -dependent deacetylase
that regulates mitochondrial energy metabolism. The role of H2S in energy
metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3
expression; however, this role remains to be elucidated. We hypothesized that
exogenous H2S could switch cardiac energy metabolic substrate preference by
lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of
db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the
treatment of high glucose, oleate, and palmitate were used as animal and cellular
models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that
increased acetylation, including 8 enzymes related to fatty acid beta-oxidation
and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts
compared to those with the treatment of NaHS. Exogenous H2S restored the
expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and
activity of SIRT3. As a result of activation of SIRT3, the acetylation level and
activity of fatty acid beta-oxidation enzyme LCAD and the acetylation of glucose
oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of
PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac
energy substrate utilization from fatty acid beta-oxidation to glucose oxidation
in DCM through regulating SIRT3 pathway. KEY MESSAGES: H2S regulated the
acetylation level and activities of enzymes in fatty acid oxidation and glucose
oxidation in cardiac tissues of db/db mice. Exogenous H2S decreased mitochondrial
acetylation level through upregulating the expression and activity of SIRT3 in
vivo and in vitro. H2S induced a switch in cardiac energy substrate utilization
from fatty acid oxidation to glucose.
PMID- 29349503
TI - Is there any difference between open and arthroscopic treatment for
osteochondritis dissecans (OCD) of the humeral capitellum: a systematic review
and meta-analysis.
AB - PURPOSE: We present a systematic review of the recent literatures regarding the
arthroscopic and open technique in fragment fixation for osteochondritis
dissecans (OCD) of the humeral capitellum and an analysis of the subjective and
objective outcomes between these two procedures. METHODS: PubMed and EMBASE were
reviewed for suitable articles relating to fragment fixation for OCD, both open
and arthroscopic. We included all studies reporting on the clinical outcomes of
these two procedures that were published in the English language. Data extracted
from each study included level of evidence, number of patients, surgical
techniques, length of follow-up, clinical outcome measures including outcome
scores, range of motion (ROM), return to sports, osseous union and complications.
We analyzed each study to determine the primary outcome measurement. RESULTS: A
total of ten studies met our inclusion criteria. Among all studies, 35
arthroscopic procedures and 107 open procedures were performed. After the
procedure, 70 patients (86.4%) in the open group returned to their sports, and 32
patients (91.4%) in the arthroscopic group returned to their sports. In the
arthroscopic group, patients gained 14.1 degrees of flexion and 9.5 degrees of
extension after surgery. In the open group, patients gained 8 degrees of flexion
and 5.7 degrees of extension. Five patients (4.7%) had complications in the open
group. No complication was found in the arthroscopic group. CONCLUSIONS: Both
open and arthroscopic lesion debridement with fragment fixation are successful in
treating unstable OCD. The arthroscopic technique may be a better choice than the
open procedure, but we need high-level evidence to determine the superiority of
the open or arthroscopic techniques in treating elbow OCD. LEVEL OF EVIDENCE:
Level III.
PMID- 29349504
TI - Oral bacterial colonization on dental implants restored with titanium or zirconia
abutments: 6-month follow-up.
AB - OBJECTIVE: This investigation aimed to characterize in a 6-month follow-up the
microbial profile of implants restored with either titanium or zirconia abutments
at the genus or higher taxonomic levels. METHODS: Twenty healthy individuals
indicative for implant-retained single restorations were investigated. Half of
participants were restored with titanium and half with zirconia abutments.
Biofilm was collected from the implant-related sites after 1, 3, and 6 months of
loading. The 16S rDNA genes were amplified and sequenced with Roche/454 platform.
RESULTS: A total of 596 species were identified in 360 samples and grouped in 18
phyla and 104 genera. Titanium- or zirconia-related sites as well as teeth showed
similar total numbers of operational taxonomic units (OTUs) colonizing surfaces
over time. Firmicutes, Proteobacteria, Fusobacteria, Bacteroidetes, and
Actinobacteria were the most prevalent phyla with significant differences between
different surfaces and time point. Unclassified genera were found in lower levels
(1.71% up to 9.57%) on titanium and zirconia samples when compared with teeth,
with no significant differences. CONCLUSION: Titanium- and zirconia-related
surfaces are promptly colonized by a bacterial community similar to those found
in the remaining adjacent teeth. Results suggest a selective adhesion of
different bacterial genotypes for either titanium or zirconia surfaces. Data also
indicate a significant interaction between the relative effects taxa, time point,
and sampling site. CLINICAL RELEVANCE: The present study disclosed a wider
spectrum of microorganisms colonizing either titanium- or zirconia-related
microbiomes in very early stage of implant colonization, revealing differences
and suggesting a probably specific mechanism for selective bacterial adhesion.
PMID- 29349505
TI - Embracing your emotions: affective state impacts lateralisation of human
embraces.
AB - Humans are highly social animals that show a wide variety of verbal and non
verbal behaviours to communicate social intent. One of the most frequently used
non-verbal social behaviours is embracing, commonly used as an expression of love
and affection. However, it can also occur in a large variety of social situations
entailing negative (fear or sadness) or neutral emotionality (formal greetings).
Embracing is also experienced from birth onwards in mother-infant interactions
and is thus accompanying human social interaction across the whole lifespan.
Despite the importance of embraces for human social interactions, their
underlying neurophysiology is unknown. Here, we demonstrated in a well-powered
sample of more than 2500 adults that humans show a significant rightward bias
during embracing. Additionally, we showed that this general motor preference is
strongly modulated by emotional contexts: the induction of positive or negative
affect shifted the rightward bias significantly to the left, indicating a
stronger involvement of right-hemispheric neural networks during emotional
embraces. In a second laboratory study, we were able to replicate both of these
findings and furthermore demonstrated that the motor preferences during embracing
correlate with handedness. Our studies therefore not only show that embracing is
controlled by an interaction of motor and affective networks, they also
demonstrate that emotional factors seem to activate right-hemispheric systems in
valence-invariant ways.
PMID- 29349506
TI - New perspectives on human multitasking.
PMID- 29349507
TI - Closing the gap: connecting sudden representational change to the subjective Aha!
experience in insightful problem solving.
AB - : Two hallmarks of insightful problem solving are thought to be suddenness in the
emergence of solution due to changes in problem representation, and the
subjective Aha! EXPERIENCE: Although a number of studies have explored the Aha!
experience, few studies have attempted to measure representational change.
Following the lead of Durso et al. (Psychol Sci 5(2):94-97, 1994) and Cushen and
Wiley (Conscious Cognit 21(3):1166-1175, 2012), in this study, participants made
importance-to-solution ratings throughout their solution attempts as a way to
assess representational change. Participants viewed a set of magic trick videos
with the task of finding out how each trick worked, and rated six action verbs
for each trick (including one that implied the correct solution) multiple times
during solution. They were also asked to indicate the extent to which they
experienced an Aha! moment. Patterns of ratings that showed a sudden change
towards a correct solution led to stronger Aha! experiences than patterns that
showed a more incremental change towards a correct solution, or a change towards
incorrect solutions. The results show a connection between sudden changes in
problem representations (leading to correct solutions) and the subjective
appraisal of solutions as an Aha! EXPERIENCE: This offers the first empirical
support for a close relationship between two theoretical constructs that have
traditionally been assumed to be related to insightful problem solving.
PMID- 29349508
TI - Impact of intervention time on hospital survival in patients requiring emergent
airway management: a preliminary study.
AB - BACKGROUND: The time in the day of intervention for physiological deterioration
reportedly impacts patient outcomes. This study aimed at determining the impact
of the time of ETI on hospital survival in critically ill patients. METHODS:
Between January 2014 and December 2016, 151 patients who underwent emergency
tracheal intubation (ETI) by the airway response team (ART) in the general wards
of a tertiary referral center were retrospectively reviewed. Patients were
divided into two groups based on the time of ETI (daytime group, 8:00 a.m.-4:00
p.m., n = 57, mean age 63.5 +/- 14.1 years; nighttime group, 4:00 p.m.-8:00 a.m.,
n = 94, mean age 60.4 +/- 14.9 years). Data regarding demographic information,
comorbidities, trigger events for intubation, survival-to-discharge rates, acute
physiology and chronic health evaluation II (APACHE II), ventilator-free days,
and airway techniques were collected. RESULTS: There was no significant
difference in sex, age, body mass index, APACHE II, or comorbidities between the
two groups, except that a higher proportion of patients presented with
arrhythmias (21.1 vs. 8.5%, p = 0.028) and received fiberoptic intubation (24.6
vs. 11.7%, p = 0.039) in the daytime group than in the nighttime group. The time
of the ART arrival after call was also shorter in daytime than that in nighttime
(6.1 +/- 1.4 vs. 10.5 +/- 3.2 min, respectively, p < 0.001). There were no
differences in the survival-to-discharge rate (45.6 vs. 43.6%, p = 0.811),
ventilator-free days, or trigger events between the two groups. CONCLUSIONS:
Emergent tracheal intubation in the nighttime may not have negative impact on the
survival-to-discharge rate compared with that performed in the daytime.
PMID- 29349509
TI - Complex issues in new ultrasound-guided nerve blocks: how to name, where to
inject, and how to publish.
AB - The recent development of ultrasound-guide nerve block has led to innovation in
anesthesia and pain clinics. However, it has also led to some complex issues,
including (1) how to name a new technique, (2) the appropriateness of an
intramuscular approach, and (3) how to publicize a new technique. This review
addresses naming strategy, feasibility of intramuscular approach block, and
methods of publication. First, researchers and authors should pay attention to
appropriate nomenclature for the term 'approach', 'compartment block', and 'nerve
block' for a new block. Second, it is lack of evidences to facilitate muscle
injection, and adequate preparation and adherence to proper technique for
intramuscular approach block should be considered; confirmation of abnormal signs
at the injection area, use of a thin needle and the lowest concentration and
volume of local anesthetic without supplementation with steroid or epinephrine,
compressing hemostasis, and sufficient interval of the blocks. Third, adequate
dissemination of information would also be necessary through publication in
appropriate media. We hope this review boost reasonable development of nerve
block.
PMID- 29349510
TI - Uncertain effect of preventative shoulder rehabilitation for patients who
underwent total laryngectomy with neck dissection.
AB - INTRODUCTION: Total laryngectomy (TL) with neck dissection (ND) is considered as
crucial management for advanced-stage of laryngeal cancer. Shoulder dysfunction
has long been recognized as a potential complication resulting from neck
dissection. The aim of this study was to evaluate the effect of early
prophylactic rehabilitation program in patients who underwent TL with ND.
METHODS: A prospective, nonrandomized design was used. Seventy-six participants
who underwent TL with ND were assigned into either an intervention or a control
group. The control group received current standard care with no formal shoulder
exercise provided, while the intervention group attended early preventive
rehabilitation lasting 12 weeks. Participants were assessed at baseline, and at 3
and 6 months after surgery. Measured outcomes included shoulder function and
patient-reported quality of life. General linear models with repeated measures
were used to examine outcome changes in both groups over the designated
assessment intervals. RESULTS: Improvement in shoulder function and patient
reported quality of life were both statistically significant over time, with no
significant difference between control or intervention groups, indicating little
or no benefit of preventative intervention on shoulder function outcomes.
Analysis involving five subscales and the summary score of the quality of life
questionnaire had only statistically significant improvement over time for both
the control or intervention groups, except for physical well-being domain which
had statistical significance both over time and between the control and
intervention groups. CONCLUSION: In this study, preventative exercise program
initiated immediately after surgery had a limited impact on both shoulder
function and perceived quality of life.
PMID- 29349511
TI - Treatment of severe periodontitis with a laser and light-emitting diode (LED)
procedure adjunctive to scaling and root planing: a double-blind, randomized,
single-center, split-mouth clinical trial investigating its efficacy and patient
reported outcomes at 1 year.
AB - Broad methodological heterogeneity makes the literature on the clinical effects
of laser treatment in periodontitis, both as monotherapy and adjunct to non
surgical therapy, which is difficult to interpret. The present split-mouth study
was performed: (i) to determine the efficacy and safety of a photoablative
photodynamic diode laser therapy, including antiseptic LED irradiation, in
adjunct to scaling and root planing (iPAPD+SRP) vs. sham-treatment+SRP for the
treatment of diffuse severe periodontitis and (ii) to estimate the patient
reported outcomes. Twenty-four patients with severe periodontitis were treated
with iPAPD+SRP or sham-treatment+SRP. iPAPD+SRP consisted of the following: (1)
intra-/extra-pocket de-epithelization with photoablative lambda 810 nm laser, (2)
disinfection with lambda 405 nm LED, (3) SRP, and (4) 10 weekly antiseptic/anti
inflammatory photodynamic treatments with lambda 635 nm laser and 0.1% toluidine
blue as photosensitizer. Clinical and cytofluorescent periodontal markers and
patient-reported results were analyzed. At 1-year follow-up, both groups showed a
significant reduction of several severity markers of periodontitis, namely
probing depth (PD) and bleeding on probing (BoP), as well as of bacteria,
polymorphonuclear cells, erythrocytes and damaged epithelial cells in exfoliative
samples, as compared with day 0. The quadrants subjected to iPAPD+SRP showed
significantly better values of these parameters as well as of clinical attachment
level (CAL) as compared with those undergoing sham-treatment+SRP. The patients'
perceived pain/discomfort, and overall liking was also in favor of the iPAPD+SRP
treatment. This study confirms the efficacy of combined phototherapy in adjunct
to SRP which had emerged from previous clinical trials, extending its field of
application to severe periodontitis.
PMID- 29349512
TI - Photobiomodulation induces in vitro re-epithelialization via nitric oxide
production.
AB - Photobiomodulation is a widely used tool in regenerative medicine thanks to its
ability to modulate a plethora of physiological responses. Wound re
epithelialization is strictly regulated by locally produced chemical mediators,
such as nitric oxide (NO), a highly reactive free radical generated by the nitric
oxide synthase (NOS) enzymatic family. In this study, it has been hypothesized
that a 980-nm low-level laser stimulation could increase NO production in human
keratinocytes and that such event might be directly related to the re
epithelialization process. Human keratinocytes were irradiated with increasing
energy outputs (10-75 J) in the absence or presence of L-NAME, a NOS inhibitor.
Laser stimulation induced an increase in NO production, resulting in an energy
dependent increase in both keratinocytes proliferation and re-epithelialization
ability. The direct link between increased NO production and the observed
physiological responses was confirmed by their inhibition in L-NAME pre-treated
samples. Since NO production increase is a quick event, it is conceivable that it
is due to an increase in existing NOS activity rather than to a de novo protein
synthesis. For this reason, it could be hypothesized that photobiomodulation
derived NO positive effects on keratinocytes behavior might rely on a near
infrared mediated increase in NOS conformational stability and cofactors as well
as substrate binding ability, finally resulting in an increased enzymatic
activity.
PMID- 29349513
TI - 3D-QSAR study of steroidal and azaheterocyclic human aromatase inhibitors using
quantitative profile of protein-ligand interactions.
AB - Aromatase is a member of the cytochrome P450 superfamily responsible for a key
step in the biosynthesis of estrogens. As estrogens are involved in the control
of important reproduction-related processes, including sexual differentiation and
maturation, aromatase is a potential target for endocrine disrupting chemicals as
well as breast cancer therapy. In this work, 3D-QSAR combined with quantitative
profile of protein-ligand interactions was employed in the identification and
characterization of critical steric and electronic features of aromatase
inhibitor complexes and the estimation of their quantitative contribution to
inhibition potency. Bioactivity data on pIC50 values of 175 steroidal and 124
azaheterocyclic human aromatase inhibitors (AIs) were used for the 3D-QSAR
analysis. For the quantitative description of the effects of the hydrophobic
contact and nitrogen-heme-iron coordination on aromatase inhibition, the
hydrophobicity density field model and the smallest dual descriptor Deltaf(r) S
were introduced, respectively. The model revealed that hydrophobic contact and
nitrogen-heme-iron coordination primarily determines inhibition potency of
steroidal and azaheterocyclic AIs, respectively. Moreover, hydrogen bonds with
key amino acid residues, in particular Asp309 and Met375, and interaction with
the heme-iron are required for potent inhibition. Phe221 and Thr310 appear to be
quite flexible and adopt different conformations according to a substituent at 4-
or 6-position of steroids. Flexible docking results indicate that proper
representation of the residues' flexibility is critical for reasonable
description of binding of the structurally diverse inhibitors. Our results
provide a quantitative and mechanistic understanding of inhibitory activity of
steroidal and azaheterocyclic AIs of relevance to adverse outcome pathway
development and rational drug design.
PMID- 29349514
TI - NB-UVB irradiation downregulates keratin-17 expression in keratinocytes by
inhibiting the ERK1/2 and STAT3 signaling pathways.
AB - Keratin-17 (K17) is a cytoskeletal protein produced by keratinocytes (KCs), which
is overexpressed in psoriasis and may play a pivotal role in its pathogenesis.
Narrow-band ultraviolet B (NB-UVB) irradiation is used as a general treatment for
psoriasis, although its impact on K17 expression has yet to be determined. In
this study, we aimed to investigate the effect of NB-UVB irradiation on K17
expression and its signaling pathways. After exposure to NB-UVB irradiation,
immortalized human keratinocytes (HaCaT cells) were analyzed by flow cytometry,
CCK-8 assays and transmission electron microscopy to examine proliferation.
Meanwhile, K17 expression in primary human epithelial keratinocytes was detected
by quantitative real-time polymerase chain reaction (qRT-PCR), western blot
analysis and immunofluorescence. HaCaT cells pre-incubated with PD-98059 and
piceatannol were subjected to western blot analysis to examine ERK1/2 and STAT3
phosphorylation. The ears of mice treated with imiquimod (IMQ) and irradiated by
NB-UVB were taken to examine K17 expression by qRT-PCR, western blot analysis,
and immunofluorescence. Our results showed that 400 mJ/cm2 of NB-UVB irradiation
was the maximum tolerable dose for HaCaT cells and could cause inhibited HaCaT
cell proliferation and moderate increase of the early apoptosis. Furthermore, NB
UVB irradiation could downregulate K17 expression by inhibiting the ERK1/2 and
STAT3 signaling pathways. In experiments conducted in vivo, NB-UVB irradiation
with doses of MED or higher could eliminate the IMQ-induced psoriasis-like
dermatitis and inhibit K17 expression. These results indicated that NB-UVB
irradiation may eliminate chronic psoriatic plaques by suppressing K17 expression
via the ERK1/2 and STAT3 signaling pathways.
PMID- 29349515
TI - Matrix metalloproteinase-2 and -9 activity levels increase in cutaneous lupus
erythematosus lesions and correlate with disease severity.
AB - Lupus erythematosus is a chronic autoimmune disease characterized by remissions
and exacerbations. Accumulated evidence indicated that matrix metalloproteinases
(MMPs) are upregulated in inflammatory cells of cutaneous lupus erythematosus
(CLE); however, the activity levels of these proteases have remained
uncharacterized. To elucidate the significance of MMP-2, MMP-9, and TIMP-1 in CLE
pathogenesis, gelatin zymography was used to investigate pro and active levels of
MMP-2 and MMP-9 in lesional and perilesional skin biopsies obtained from twenty
two CLE patients. TIMP-1 protein levels were detected by ELISA in the biopsy
specimens. The correlation between biochemical parameters and clinical
characteristics of the disease was also evaluated. Significantly higher levels of
active MMP-2, active MMP-9, proMMP-9, active/proMMP-2, and TIMP-1 were detected
in lesional skin samples. Besides, the active/proMMP-9 was elevated in female and
smoking patients. Active MMP-9 levels and active/proMMP-9 were also increased in
elderly patients. Active MMP-9 levels were lower in patients who had smaller
total damage score. Consistently, active/proMMP-9 and active/proMMP-2 were
positively correlated with CLASI. Interestingly, in hydroxychloroquine or topical
corticosteroid-treated patients, MMP-2/-9 activity levels were found to be higher
compared to untreated patients. These findings suggest that increased MMP-2 and
MMP-9 activities may contribute to the pathogenesis of CLE and cutaneous disease
severity.
PMID- 29349516
TI - New perspectives in the history of twentieth-century life sciences: historical,
historiographical and epistemological themes.
AB - The history of twentieth-century life sciences is not exactly a new topic.
However, in view of the increasingly rapid development of the life sciences
themselves over the past decades, some of the well-established narratives are
worth revisiting. Taking stock of where we stand on these issues was the aim of a
conference in 2015, entitled "Perspectives for the History of Life Sciences"
(Munich, Oct 30-Nov 1, 2015). The papers in this topical collection are based on
work presented and discussed at and around this meeting. Just as the conference,
the collection aims at exploring fields in the history of life sciences that
appear understudied, sources that have been overlooked, and novel ways of
engaging with this material. The papers convened in this collection may not be
representative of the field as a whole; but we feel that they do indicate some
elements that have received emphasis in recent years, and may become more central
in the years to come, such as the history of previously neglected contexts and
domains of the life sciences, the question of continuity and change on the level
of practices, the history of complexity and diversity in twentieth-century life
sciences and the reconsideration of the relationship between history and
philosophy of life sciences.
PMID- 29349517
TI - A novel genomic signature predicting FDG uptake in diverse metastatic tumors.
AB - BACKGROUND: Building a universal genomic signature predicting the intensity of
FDG uptake in diverse metastatic tumors may allow us to understand better the
biological processes underlying this phenomenon and their requirements of glucose
uptake. METHODS: A balanced training set (n = 71) of metastatic tumors including
some of the most frequent histologies, with matched PET/CT quantification
measurements and whole human genome gene expression microarrays, was used to
build the signature. Selection of microarray features was carried out exclusively
on the basis of their strong association with FDG uptake (as measured by
SUVmean35) by means of univariate linear regression. A thorough bioinformatics
study of these genes was performed, and multivariable models were built by
fitting several state of the art regression techniques to the training set for
comparison. RESULTS: The 909 probes with the strongest association with the
SUVmean35 (comprising 742 identifiable genes and 62 probes not matched to a
symbol) were used to build the signature. Partial least squares using three
components (PLS-3) was the best performing model in the training dataset cross
validation (root mean square error, RMSE = 0.443) and was validated further in an
independent validation dataset (n = 13) obtaining a performance within the 95% CI
of that obtained in the training dataset (RMSE = 0.645). Significantly
overrepresented biological processes correlating with the SUVmean35 were
identified beyond glycolysis, such as ribosome biogenesis and DNA replication
(correlating with a higher SUVmean35) and cytoskeleton reorganization and
autophagy (correlating with a lower SUVmean35). CONCLUSIONS: PLS-3 is a signature
predicting accurately the intensity of FDG uptake in diverse metastatic tumors.
FDG-PET might help in the design of specific targeted therapies directed to
counteract the identified malignant biological processes more likely activated in
a tumor as inferred from the SUVmean35 and also from its variations in response
to antineoplastic treatments.
PMID- 29349519
TI - Agonistic autoantibodies against adrenergic receptors correlating with
antihypertensive therapy in long-standing diabetes type 2.
PMID- 29349518
TI - Checkpoint Inhibitors, Palliative Care, or Hospice.
AB - PURPOSE: Checkpoint (CTLA-4, PD-1, and PD-L1) inhibitors have changed the face of
oncology. A subset of patients enjoys long, gratifying treatment responses.
Unfortunately, most patients do not respond even when expressing favorably
markers such as PD-L1. Checkpoint inhibitors are largely palliative (though a
subset have long-term cancer responses) and as such patient-related outcome
measures should be included when evaluating benefits. The purpose of this review
is to place checkpoint inhibitor trials within a palliation context. Included is
a discussion on potential adverse effects on end-of-life care. RECENT FINDINGS:
Pivotal studies have presented efficacy and safety data but we have little
published data on quality of life or symptom responses. Extension of life is
approximately 2-3 months with some long-term responses in a minority of patients.
The cost of checkpoint inhibitors is high for utility (as measured by quality
adjusted life-year saved) and ranges from 81,000 to over 200,000 USD for quality
adjusted life-year saved. Adverse effects were suboptimally reported in multiple
studies. Meaningful responses in many trials as defined by the European Society
of Medical Oncology are modest. Because at least for now, checkpoint inhibitors
are used in advanced cancer and largely palliative patients should be seen by
palliative specialists, symptoms related to cancer assessed, and advanced
directives addressed. Treatment-related autoimmune diseases represent toxicities
which oncologists and palliative specialists must understand. This means that
palliative care specialists should know about the benefits and adverse effects of
these agents. Whether checkpoint inhibitors increase or decrease aggressive care,
hospice referrals, and costs at the end of life is yet to be determined.
PMID- 29349520
TI - Experimental Study of 5-fluorouracil Encapsulated Ethosomes Combined with CO2
Fractional Laser to Treat Hypertrophic Scar.
AB - OBJECTIVE: This study is designed to explore permeability of ethosomes
encapsulated with 5-florouracil (5-FU) mediated by CO2 fractional laser on
hypertrophic scar tissues. Moreover, therapeutic and duration effect of CO2
fractional laser combined with 5-FU encapsulated ethosomes in rabbit ear
hypertrophic scar model will be evaluated. METHODS: The permeated amount of 5-FU
and retention contents of 5-FU were both determined by high-performance liquid
chromatography (HPLC). Fluorescence intensities of ethosomes encapsulated with 5
FU (5E) labeled with Rodanmin 6GO (Rho) were measured by confocal laser scanning
microscopy (CLSM). The permeability promotion of 5E labeled with Rho in rabbit
ear hypertrophic scar mediated by CO2 fractional laser was evaluated at 0 h, 6 h,
12 h, 24 h, 3 days and 7 days after the irradiation. The opening rates of the
micro-channels were calculated according to CLSM. The therapeutic effect of 5EL
was evaluated on rabbit ear hypertrophic scar in vivo. Relative thickness of
rabbit ear hypertrophic scar before and after the treatment was measured by
caliper method. Scar elevation index (SEI) of rabbit ear hypertrophic scar was
measured using H&E staining. RESULTS: The data showed that the penetration amount
of 5EL group was higher than 5E group (4.15 +/- 2.22 vs. 0.73 +/- 0.33; p < 0.05)
after 1-h treatment. Additionally, the penetration amount of 5EL was higher than
that of the 5E group (107.61 +/- 13.27 vs. 20.73 +/- 3.77; p < 0.05) after 24-h
treatment. The retention contents of the 5EL group also showed higher level than
5E group (24.42 +/- 4.37 vs.12.25 +/- 1.64; p < 0.05). The fluorescence intensity
of Rho in hypertrophic scar tissues of the 5EL group was higher than that of the
5E group at different time points (1, 6, and 24 h). The opening rates of the
micro-channels were decreased gradually within 24 h, and micro-channels were
closed completely 3 days after the irradiation by CO2 fractional laser. The
relative thickness and SEI of rabbit ear hypertrophic scar after 7 days of
treatment in the 5EL group were significantly lower than the 5E group.
CONCLUSION: CO2 fractional laser combined with topical 5E can be effective in the
treatment of hypertrophic scar in vivo and supply a novel therapy method for
human hypertrophic scar.
PMID- 29349521
TI - Recent developments in the synthesis and applications of dihydropyrimidin-2(1H)
ones and thiones.
AB - Dihydropyrimidin-2(1H)-ones/thiones (DHPMs) are important heterocyclic compounds
owing to their excellent biological activities and have been widely utilized in
pharmaceutical applications. Recently, numerous DHPM derivatives have been
prepared. This review covers the synthesis of DHPMs and improved procedures for
the preparation of DHPMs from 1995 to 2016.
PMID- 29349523
TI - Prognostic factors of pediatric glaucoma: a retrospective study.
AB - PURPOSE: To correlate the features of certain types of infantile glaucoma with
the progression and the prognosis of the disease, highlighting probable risk
factors. METHODS: Seventy-six patients with pediatric glaucoma were recruited in
this retrospective study. All patients underwent ophthalmological examination in
the Department of Ophthalmology of the Saarland University Medical Center from
January 2001 to December 2012. Our pediatric patients were classified into four
different categories of glaucoma: (1) primary congenital glaucoma (presenting
buphthalmus), (2) aniridia-related glaucoma, (3) Peters/Rieger's anomaly-related
glaucoma and (4) congenital cataract-related glaucoma. Personal data comprised
age, sex, nationality, systemic diseases and gestational age. The best-corrected
visual acuity (BCVA), the cup-disk ratio (CDR), the intraocular pressure (IOP),
the corneal diameter and thickness, along with the Haab striae and corneal haze,
were recorded. RESULTS: The majority of the children were male (58%) and suffered
from aniridia-related glaucoma (38%). Children with aniridia exhibited the worst
BCVA. The CDR and IOP were significantly higher in children with primary
congenital glaucoma, compared to the other groups, at the first visit. Those
children also were with the largest corneal diameter and prevalence of Haab
striae compared to the rest groups, whereas corneal haze was found more often and
was more pronounced in children with Peters/Rieger's syndrome. CONCLUSIONS: We
concluded that glaucoma was earlier detected in children with primary congenital
glaucoma, who exhibited increased corneal diameter and high percentage of Haab
striae comparing to the other groups. However, these children responded
successfully to any therapeutic intervention, exhibiting better BCVA and IOP
values than the rest groups at the second visit.
PMID- 29349522
TI - Team-Based Care with Pharmacists to Improve Blood Pressure: a Review of Recent
Literature.
AB - PURPOSE OF REVIEW: We review studies published since 2014 that examined team
based care strategies and involved pharmacists to improve blood pressure (BP). We
then discuss opportunities and challenges to sustainment of team-based care
models in primary care clinics. RECENT FINDINGS: Multiple studies presented in
this review have demonstrated that team-based care including pharmacists can
improve BP management. Studies highlighted the cost-effectiveness of a team-based
pharmacy intervention for BP control in primary care clinics. Little information
was found on factors influencing sustainability of team-based care interventions
to improve BP control. Future work is needed to determine the best populations to
target with team-based BP programs and how to implement team-based approaches
utilizing pharmacists in diverse clinical settings. Future studies need to not
only identify unmet clinical needs but also address reimbursement issues and
stakeholder engagement that may impact sustainment of team-based care
interventions.
PMID- 29349524
TI - [Qualification and classification of medical apps : What should be noted and what
is BfArM's contribution?]
AB - Smartphones and tablets with their nearly unlimited number of different
applications have become an integral part of everyday life. Thus, mobile devices
and applications have also found their way into the healthcare sector.For
developers, manufacturers, or users as well, it is often difficult to decide
whether a mobile health application is a medical device.In this context, it is
extremely important for manufacturers to decide at an early stage of the
development whether the product is to be introduced into the market as a medical
device and is therefore subject to the legislation on medical devices.This
article first presents the regulatory framework and subsequently introduces the
reader to the Federal Institute for Drugs and Medical Devices' (BfArM) view of
the criteria for differentiating between apps as non-medical products and apps as
medical apps as well as the classification thereof. Various examples are
presented to demonstrate how these criteria are applied practically and options
that support developers and manufacturers in their decision making are shown. The
article concludes with a reference to current developments and offers a
perspective on the new European medical device regulations MDR/IVDR (Medical
Device Regulation/In-Vitro Diagnostic Regulation) as well as on future challenges
regarding medical apps.
PMID- 29349525
TI - Value of CT pulmonary angiography to predict short-term outcome in patient with
pulmonary embolism.
AB - To evaluate the role of CT pulmonary angiography (CTPA) in the assessment of
pulmonary embolism (PE) severity and the related CT cardiac changes, reflecting
the clinical status of the patients and predicting the outcome. A prospective
study of 184 patients presented with suspicious acute PE. All patients underwent
CTPA followed by ECHO. Pulmonary artery obstructive index (PAOI) using Qanadli
Score was calculated and cardiac changes recorded. The patients' outcome was
followed up for 30 days. Only 150 patients completed the study; 26.7% needed ICU
admission while 13.3% died during follow-up. There was a significant relationship
between the PAOI and the risk classification, right ventricular dysfunction (RVD)
diagnosed by ECHO and the patients' short outcome. We found PAOI cut off value
45% for mortality and 35% for ICU admission and 27.5% for RVD with 60, 75 and 90%
sensitivity and 80, 73.3 and 68.6% specificity respectively. CT RV/LV ratio was
the most sensitive parameter to predict RV dysfunction followed by pulmonary
artery diameter. CTPA is not only used for diagnosis but also to assess the
severity of PE, the effect on the right ventricular function and subsequently the
need for ICU admission and prediction of the outcome.
PMID- 29349526
TI - Normal pulmonary artery and branch pulmonary artery sizes in children.
AB - To establish standards for pulmonary artery and branch pulmonary artery (PA and
BPA) effective diameter (ED) and cross-sectional area (CSA) by using computed
tomography (CT) data in children of a wide range of sizes and investigate the
roundness of arteries. The ED (average of short and long axes) and CSA for the PA
and BPA were measured using 1-mm collimation double-oblique reconstructions.
Ordinary least squares regression was used to investigate models with various
functional forms that related ED and CSA to patient size. Aspect ratio (AR), the
short axis divided by long axis, was measured to evaluate roundness. The ideal
diameter derived from CSA measurements was compared to ED, short axis, and long
axis measurements. 108 CT examinations were analyzed in children without reason
for abnormal PA size who ranged in age from 0 to 18 years (mean, 10.9 years; SD,
5.9 years). Interrater reliability was excellent. Data were modeled using a
natural log-transformed response variable and a linear term for height as the
independent variable. AR for the PA, right pulmonary artery, and left pulmonary
artery measured < 0.9 for 38, 55, and 37%, respectively, indicating that many
arteries are not round. Ideal diameter was not significantly different than ED
but was for short- and long-axis diameter measurements. Normal ED and CSA for PA
and BPA were determined for children of different sizes. Measurements outside of
the normal range are consistent with dilatation or stenosis. Single diameter
techniques are likely to introduce error.
PMID- 29349527
TI - Genetic Test Reporting and Counseling for Melanoma Risk in Minors May Improve Sun
Protection Without Inducing Distress.
AB - Genetic testing of minors is advised only for conditions in which benefits of
early intervention outweigh potential psychological harms. This study
investigated whether genetic counseling and test reporting for the CDKN2A/p16
mutation, which confers highly elevated melanoma risk, improved sun protection
without inducing distress. Eighteen minors (Mage = 12.4, SD = 1.9) from melanoma
prone families completed measures of protective behavior and distress at
baseline, 1 week (distress only), 1 month, and 1 year following test disclosure.
Participants and their mothers were individually interviewed on the psychological
and behavioral impact of genetic testing 1 month and 1 year post-disclosure.
Carriers (n = 9) and noncarriers (n = 9) reported significantly fewer sunburns
and a greater proportion reported sun protection adherence between baseline and 1
year post-disclosure; results did not vary by mutation status. Anxiety symptoms
remained low post-disclosure, while depressive symptoms and cancer worry
decreased. Child and parent interviews corroborated these findings. Mothers
indicated that genetic testing was beneficial (100%) because it promoted risk
awareness (90.9%) and sun protection (81.8%) without making their children scared
(89.9%); several noted their child's greater independent practice of sun
protection (45.4%). In this small initial study, minors undergoing CDKN2A/p16
genetic testing reported behavioral improvements and consistently low distress,
suggesting such testing may be safely implemented early in life, allowing greater
opportunity for risk-reducing lifestyle changes.
PMID- 29349528
TI - Steps to Getting Your Manuscript Published in a High-Quality Medical Journal.
AB - Publication of your research represents the culmination of your scientific
activities. The key to getting manuscripts accepted is to make them
understandable and informative so that your colleagues will read and benefit from
them. We describe key criteria for acceptance of manuscripts and outline a multi
step process for writing the manuscript. The likelihood that a manuscript will be
accepted by a major journal is significantly increased if the manuscript is
written in polished and fluent scientific English. Although scientific quality is
the most important consideration, clear and concise writing often makes the
difference between acceptance and rejection. As with any skill, efficient writing
of high-quality manuscripts comes with experience and repetition. It is very
uncommon for a manuscript to be accepted as submitted to a journal. Thoughtful
and respectful responses to the journal reviewers' comments are critical. Success
in scientific writing, as in surgery, is dependent on effort, repetition, and
commitment. The transfer of knowledge through a well-written publication in a
high-quality medical journal will have an impact not only in your own institution
and country, but also throughout the world.
PMID- 29349529
TI - Esophageal Cancer Surgery: Spontaneous Centralization in the US Contributed to
Reduce Mortality Without Causing Health Disparities.
AB - BACKGROUND: Improvement in mortality has been shown for esophagectomies performed
at high-volume centers. OBJECTIVE: This study aimed to determine if
centralization of esophageal cancer surgery occurred in the US, and to establish
its impact on postoperative mortality. In addition, we aimed to analyze the
relationship between regionalization of cancer care and health disparities.
METHODS: A retrospective population-based analysis was performed using the
National Inpatient Sample for the period 2000-2014. Adult patients (>= 18 years
of age) diagnosed with esophageal cancer and who underwent esophagectomy were
included. Yearly hospital volume was categorized as low (< 5 procedures),
intermediate (5-20 procedures), and high (> 20 procedures). Multivariable
analyses on the potential effect of hospital volume on patient outcomes were
performed, and the yearly rate of esophagectomies was estimated using Poisson
regression. RESULTS: A total of 5235 patients were included. Esophagectomy at low
[odds ratio (OR) 2.17] and intermediate-volume (OR 1.62) hospitals, compared
with high-volume hospitals, was associated with a significant increase in
mortality. The percentage of esophagectomies performed at high-volume centers
significantly increased during the study period (29.2-68.5%; p < 0.0001). The
trend towards high-volume hospitals was different among the different US regions:
South (7.7-54.3%), West (15.0-67.6%), Midwest (37.3-67.7%), and Northeast (55.8
86.8%) [p < 0.0001]. Overall, the mortality rate of esophagectomy dropped from
10.0 to 3.5% (p = 0.006), with non-White race, public insurance, and low
household income patients also showing a significant reduction in mortality.
CONCLUSIONS: A spontaneous centralization for esophageal cancer surgery occurred
in the US. This process was associated with a decrease in the mortality rate,
without contributing to health disparities.
PMID- 29349530
TI - Photocatalytic activity of attapulgite-TiO2-Ag3PO4 ternary nanocomposite for
degradation of Rhodamine B under simulated solar irradiation.
AB - An excellent ternary composite photocatalyst consisting of silver orthophosphate
(Ag3PO4), attapulgite (ATP), and TiO2 was synthesized, in which heterojunction
was formed between dissimilar semiconductors to promote the separation of photo
generated charges. The ATP/TiO2/Ag3PO4 composite was characterized by SEM, XRD,
and UV-vis diffuse reflectance spectroscopy. The co-deposition of Ag3PO4 and TiO2
nanoparticles onto the surface of ATP forms a lath-particle structure. Compared
with composite photocatalysts consisting of two phases, ATP/TiO2/Ag3PO4 ternary
composite exhibits greatly improved photocatalytic activity for degradation of
rhodamine B under simulated solar irradiation. Such ternary composite not only
improves the stability of Ag3PO4, but also lowers the cost by reducing
application amount of Ag3PO4, which provides guidance for the design of Ag3PO4-
and Ag-based composites for photocatalytic applications.
PMID- 29349531
TI - An "All-In-One" Pharmacophoric Architecture for the Discovery of Potential Broad
Spectrum Anti-Flavivirus Drugs.
AB - A precipitous increase in the number of flaviviral infections has been noted over
the last 5 years. Despite these outbreaks, treatment protocols for infected
individuals remain ambiguous. Numerous studies have identified NITD008 as a
potent flavivirus inhibitor; however, clinical testing was dismissed due to
undesirable toxic effects. The binding landscape of NITD008 in complex with five
detrimental flaviviruses at the RNA-dependent RNA polymerase active sites was
explored. An "all-in-one" pharmacophore model was created for the design of small
molecules that may inhibit a broad spectrum of flaviviruses. This pharmacophore
model approach serves as a robust cornerstone, thus assisting medicinal experts
in the composition of multifunctional inhibitors that will eliminate cross
resistance and toxicity and enhance patient adherence.
PMID- 29349532
TI - A Novel Approach in Treatment of Tuberculosis by Targeting Drugs to Infected
Macrophages Using Biodegradable Nanoparticles.
AB - Mycobacterium tuberculosis, the causative agent of tuberculosis is now causing
death of more than 10 million people. Because of the development of drug
resistant TB, drug delivery to the infected site through nanoparticle had been
studied for long time. Nanoparticles indicate different sorts of association with
the natural particles of the body. Nanoparticles can be used as controlled or
specific drug delivery system. It can be through temporal controlled or can be
distribution controlled. Glucose polymer-based nanoparticles might play an
important role as drug delivery system in case of targeted drug delivery in the
infected site of the body or in infected macrophages, as they are biodegradable
so there should not be any side effects of these particles in the body and also
they show very slow immune response. CD4, Beta 1, TGFb-1, IL-2, IL-13 SEC14L1,
GUSB, BPI, and CCR7 are major biomarkers secreted after infection of this
bacterium by the macrophages which can be used for targeted drug delivery in
infected macrophages. As these markers can be used for delivery of drugs at
destined position, they can be very beneficial in reducing toxicities of
antituberculer drugs to the other uninfected sites and in operating only the
infected macrophages.
PMID- 29349533
TI - Hendra Virus Spillover is a Bimodal System Driven by Climatic Factors.
AB - Understanding environmental factors driving spatiotemporal patterns of disease
can improve risk mitigation strategies. Hendra virus (HeV), discovered in
Australia in 1994, spills over from bats (Pteropus sp.) to horses and thence to
humans. Below latitude - 22 degrees , almost all spillover events to horses occur
during winter, and above this latitude spillover is aseasonal. We generated a
statistical model of environmental drivers of HeV spillover per month. The model
reproduced the spatiotemporal pattern of spillover risk between 1994 and 2015.
The model was generated with an ensemble of methods for presence-absence data
(boosted regression trees, random forests and logistic regression). Presences
were the locations of horse cases, and absences per spatial unit (2.7 * 2.7 km
pixels without spillover) were sampled with the horse census of Queensland and
New South Wales. The most influential factors indicate that spillover is
associated with both cold-dry and wet conditions. Bimodal responses to several
variables suggest spillover involves two systems: one above and one below a
latitudinal area close to - 22 degrees . Northern spillovers are associated with
cold-dry and wet conditions, and southern with cold-dry conditions. Biologically,
these patterns could be driven by immune or behavioural changes in response to
food shortage in bats and horse husbandry. Future research should look for
differences in these traits between seasons in the two latitudinal regions. Based
on the predicted risk patterns by latitude, we recommend enhanced preventive
management for horses from March to November below latitude 22 degrees south.
PMID- 29349534
TI - Psoriasis: from Pathogenesis to Targeted Therapies.
AB - Over the last decade, the management of psoriasis has witnessed a paradigm shift.
Thanks to the increasing knowledge about the pathogenesis of psoriasis, targeted
treatments with monoclonal antibodies have been developed. These antibodies,
which target the pathogenic TNF/IL-23/IL-17-pathway, were shown to be safe and
efficacious in the management of most patients with moderate to severe chronic
plaque psoriasis. Recently, molecular and genetic studies in pustular and
erythrodermic psoriasis have identified additional inflammatory pathways,
providing evidence that psoriasis is a heterogeneous disease and highlighting the
requirement for personalized disease characterization for treatment optimization.
In this article, we will review these advances and provide an update on the
currently available treatment arsenal. We discuss the efficacy and safety profile
of these individual therapeutic agents and describe their use in special
indications. We will also describe the current understanding of psoriasis as a
systemic disease associated with multiple comorbidities and illustrate its impact
in the management of psoriatic patients. Finally, we discuss ongoing therapeutic
developments as well as unmet needs and future perspectives in the field of
psoriasis.
PMID- 29349535
TI - Mycobacterium xenopi Genotype Associated with Clinical Phenotype in Lung Disease.
AB - Mycobacterium xenopi is responsible for pulmonary disease (PD) in Europe and
Canada. Despite its high prevalence and increasing clinical importance, little is
known about the genetic diversity of M. xenopi. Through a prospective study for
M. xenopi strain type and the relation to clinical phenotype, 39 patients with M.
xenopi PD were analyzed. Our study demonstrated that sequence type (ST) 5 was
dominant in Ontario among 15 distinct STs and caused PD in people even without
underlying lung disease, whereas disease due to non-ST5 was found almost
exclusively in patients with underlying lung disease.
PMID- 29349536
TI - Oxygen Uptake Efficiency Slope and Prediction of Post-operative Morbidity and
Mortality in Patients with Lung Cancer.
AB - OBJECTIVE: Peak oxygen consumption is a very valuable cardiopulmonary functional
parameter in pre-operative evaluation of patients with lung cancer. However, it
has several critical limitations for operability decision due to failure in
achieving maximal level of exercise test for cases. The aim of this study was to
reveal the importance of more accurate cardiopulmonary parameters that can be
calculated from data of submaximal level test, such as oxygen uptake efficiency
slope (OUES) and to determine whether it could be used in the operability
decision phase for borderline cases by means of morbidity and mortality.
MATERIALS AND METHODS: One hundred and twenty-five patients who were scheduled to
undergo lung surgery due to lung cancer were included in the study. Peak oxygen
uptake (pVO2), heart rate at the anaerobic threshold, and oxygen consumption
volume at anaerobic threshold values were obtained after performing the
cardiopulmonary exercise test. The OUES value was calculated from the ratio of
the peak VO2 value and logarithmic equivalent of the ventilatory volume (VE). The
following equation was used for determining OUES: VO2/log10 VE. RESULTS: The peak
VO2 mean value was 21.37 +/- 4.20 mL/min/kg in patients. However, OUES mean value
was 12.44 +/- 2.11. When the metabolic parameters of the patients were compared,
a significant correlation was determined between the peak VO2 value and peak VE,
OUES, and survival (p < 0.01). CONCLUSION: This study demonstrated that OUES is
significantly correlated with peak VO2 and it does not require the performance of
maximal exercise and can be used together with peak VO2 in this patient
population when there is difficulty in making decision for surgery in patients
with lung cancer.
PMID- 29349537
TI - Timing of Spirometry May Impact Hospital Length of Stay for Cystic Fibrosis
Pulmonary Exacerbation.
AB - PURPOSE: The optimal timing of spirometry during hospitalization for acute
pulmonary exacerbation (PEx) in patients with cystic fibrosis (CF) is unclear. We
retrospectively evaluated whether measuring spirometry earlier during
hospitalization was associated with a shorter length of stay (LOS). METHODS: In
this retrospective study, we analyzed data from the electronic medical record of
CF patients 6 years of age and older admitted to a single center for acute PEx
requiring IV antibiotic therapy between 2009 and 2016. After excluding patient
encounters with missing data on covariates, random-effects linear regression was
used to predict LOS as a function of days to first pulmonary function testing
(PFT), which was spirometry for our study. RESULTS: One thousand thirty-five
hospitalizations of 242 patients met inclusion criteria, with 801 including
complete data on covariates. Mean LOS was 10 +/- 7 days, with mean time to first
PFT of 4 +/- 3 days after admission. In multivariable analysis, each additional
day to first PFT was associated with 0.97 days longer LOS (95% CI 0.29, 1.64; p =
0.005). CONCLUSIONS: As CF researchers and clinicians work to improve management
of PEx, the timing of spirometry during hospitalization remains an important
question. Obtaining objective lung function data earlier during the course of
therapy may provide information which can lead to reduced hospital LOS for PEx.
PMID- 29349538
TI - Capturing pair-wise epistatic effects associated with three agronomic traits in
barley.
AB - Genetic association mapping has been widely applied to determine genetic markers
favorably associated with a trait of interest and provide information for marker
assisted selection. Many association mapping studies commonly focus on main
effects due to intolerable computing intensity. This study aims to select several
sets of DNA markers with potential epistasis to maximize genetic variations of
some key agronomic traits in barley. By doing so, we integrated a MDR
(multifactor dimensionality reduction) method with a forward variable selection
approach. This integrated approach was used to determine single nucleotide
polymorphism pairs with epistasis effects associated with three agronomic traits:
heading date, plant height, and grain yield in barley from the barley Coordinated
Agricultural Project. Our results showed that four, seven, and five SNP pairs
accounted for 51.06, 45.66 and 40.42% for heading date, plant height, and grain
yield, respectively with epistasis being considered, while corresponding
contributions to these three traits were 45.32, 31.39, 31.31%, respectively
without epistasis being included. The results suggested that epistasis model was
more effective than non-epistasis model in this study and can be more preferred
for other applications.
PMID- 29349539
TI - Effect of the application of a bundle of three measures (intraperitoneal lavage
with antibiotic solution, fascial closure with Triclosan-coated sutures and
Mupirocin ointment application on the skin staples) on the surgical site
infection after elective laparoscopic colorectal cancer surgery.
AB - BACKGROUND: Surgical site infection (SSI) prevention bundles include the
simultaneous use of different measures, which individually have demonstrated an
effect on prevention of SSI. The implementation of bundles can yield superior
results to the implementation of individual measures. The aim of this study was
to address the effect of the application of a bundle including intraperitoneal
lavage with antibiotic solution, fascial closure with Triclosan-coated sutures
and Mupirocin ointment application on the skin staples, on the surgical site
infection after elective laparoscopic colorectal cancer surgery. METHODS: A
prospective, randomized study was performed, including patients with diagnosis of
colorectal neoplasms and plans to undergo an elective laparoscopic surgery. The
patients were randomized into two groups: those patients following standard
bundles (Group 1) and those ones following the experimental bundle with three
additional measures, added to the standard bundle. Incisional and organ space SSI
were investigated. The study was assessor-blinded. RESULTS: A total of 198
patients were included in the study, 99 in each group. The incisional SSI rate
was 16% in Group 1 and 2% in Group 2 [p = 0.007; RR = 5.6; CI 95% (1.4-17.8)].
The organ-space SSI rate was 4% in Group 1 and 0% in Group 2 [p = 0.039; RR =
1.7; CI 95% (1.1-11.6)]. Median hospital stay was 5.5 days in Group 1 and 4 days
in Group 2 (p = 0.028). CONCLUSIONS: The addition of intraperitoneal lavage with
antibiotic solution, fascial closure with Triclosan-coated sutures and Mupirocin
ointment application on the skin staples, to a standard bundle of SSI prevention,
reduces the incisional and organ-space SSI and consequently the hospital stay,
after elective laparoscopic colorectal cancer surgery (ClinicalTrials.gov
Identifier: NCT03081962).
PMID- 29349540
TI - Self-dilation for therapy-resistant benign esophageal strictures: towards a
systematic approach.
AB - BACKGROUND: Patients with therapy-resistant benign esophageal strictures (TRBES)
suffer from chronic dysphagia and generally require repeated endoscopic
dilations. For selected patients, esophageal self-dilation may improve patient's
autonomy and reduce the number of endoscopic dilations. We evaluated the clinical
course and outcomes of patients who started esophageal self-dilation at our
institution. METHODS: This study was a retrospective case series of patients with
TRBES who started esophageal self-dilation between 2012 and 2016 at the Academic
Medical Center Amsterdam. To learn self-dilation using Savary-Gilliard bougie
dilators, patients visited the outpatient clinic on a weekly basis where they
were trained by a dedicated nurse. Endoscopic dilation was continued until
patients were able to perform self-bougienage adequately. The primary outcome was
the number of endoscopic dilation procedures before and after initiation of self
dilation. Secondary outcomes were technical success, final bougie size, dysphagia
scores, and adverse events. RESULTS: Seventeen patients started with esophageal
self-dilation mainly because of therapy-resistant post-surgical (41%) and caustic
(35%) strictures. The technical success rate of learning self-bougienage was 94%
(16/17). The median number of endoscopic dilation procedures dropped from 17
[interquartile range (IQR) 11-27] procedures during a median period of 9 (IQR 6
36) months to 1.5 (IQR 0-3) procedures after the start of self-dilation (p <
0.001). The median follow-up after initiation of self-dilation was 17.6 (IQR 11.5
33.3) months. The final bougie size achieved with self-bougienage had a median
diameter of 14 (IQR 13-15) mm. All patients could tolerate solid foods (Ogilvie
dysphagia score <= 1), making the clinical success rate 94% (16/17). One patient
(6%) developed a single episode of hematemesis related to self-bougienage.
CONCLUSIONS: In this small case series, esophageal self-dilation was found to be
successful 94% of patients when conducted under strict guidance. All patients
performing self-bougienage achieved a stable situation where they could tolerate
solid foods without the need for endoscopic dilation.
PMID- 29349541
TI - Per oral endoscopic myotomy: early experience and safety of a multispecialty
approach.
AB - BACKGROUND: Per oral endoscopic myotomy (POEM) has gained increasing popularity
for treating achalasia. A multidisciplinary approach may allow safe and early
adoption of POEM into clinical practice. MATERIALS AND METHODS: We performed a
retrospective review of our initial POEM cases. All procedures were performed by
a team of interventional gastroenterologist and thoracic surgeon. We analyzed
demographics, comorbidities, achalasia subtypes, length of hospital stay,
duration of surgery, morbidity, mortality, length of myotomy, preoperative and
postoperative Eckardt scores. RESULTS: Thirty-one consecutive patients underwent
POEM during the 24-month period from January 2014 to December 2015. Eighteen
patients (58%) had prior non-operative interventions. Average duration of follow
up was 9.6 months. Seventeen patients (66.8%) had follow-up of 12 months and
longer. Average preoperative Eckardt score was 6.3 (3-10), median 6. Average
postoperative Eckardt score was 1.4 (0-8), median 1, in 1 month and an average
2.2, median 1, in 1 year. Patients with type III achalasia were most refractory
to treatment, while patients with type II had the best results. Average LOS was
1.3 days (1-5), median 1 day. Average DOS was 106 min (60-148), median 106.
Average LOM was 13 cm (10-15), with median of 13 cm. We had one 30-day mortality
secondary to coronary artery disease. Four patients had prior Heller myotomies
and underwent a posterior myotomy during POEM, with outcomes similar to patients
with no prior myotomy. CONCLUSIONS: We demonstrated safety and efficiency of a
multispecialty approach for achalasia with POEM with a low rate of complications.
PMID- 29349542
TI - Laparoscopic pancreaticoduodenectomy with reconstruction of the mesentericoportal
vein with the parietal peritoneum and the falciform ligament.
AB - BACKGROUND: With the improvement of the surgical technique of Laparoscopic
pancreaticoduodenectomy (LPD), indications will be extended to patients with
vascular invasion. With LPD, vascular grafts for reconstruction are more
frequently needed because adequate mobilization is not always done and vascular
grafts can safely facilitate reconstruction. We describe our experience of
reconstruction with the falciform ligament. METHODS: Venous reconstruction is
performed after removal of the specimen. The falciform ligament is rapidly
harvested within the same surgical field and for any size and used for lateral
reconstruction of the mesentericoportal vein. Therapeutic anticoagulation is not
needed and venous patency was assessed by postoperative CT scan. Since April 2011
and among the 93 patients who underwent LPD, four patients had this procedure.
RESULTS: The mean age was 73 years old (69-77) and 3 were women. Indications for
resection were pancreatic adenocarcinoma (n = 3) and IPMN in severe dysplasia (n
= 1) and the mean patch size of 13 mm (10-30). The mean operative time was 397
min (330-480); vascular clamping lasted 54 min (45-60), and mean blood loss was
437 ml (150-1000) and one was transfused. Resection was R0 in patients with
adenocarcinoma (n = 3). The postoperative course was uneventful in 3 patients and
one patient was re-operated for bile leak and partial venous thrombosis and redo
venous reconstruction was done. Complete venous patency was demonstrated in
patients (n = 2) who still alive 1 year after resection. CONCLUSION: Venous
resection will be more frequently done with LPD and vascular grafts more
frequently needed. Compared to other available vascular grafts (autogenous,
synthetic, cadaveric and bovine pericardium, etc), the parietal peritoneum had
the advantages of being rapidly available, easy to harvest by the laparoscopic
approach, not expensive, no need for anticoagulation and at lower risk of
infection.
PMID- 29349543
TI - Saving robots improves laparoscopic performance: transfer of skills from a
serious game to a virtual reality simulator.
AB - BACKGROUND: Residents find it hard to commit to structural laparoscopic skills
training. Serious gaming has been proposed as a solution on the premise that it
is effective and more motivating than traditional simulation. We establish
construct validity for the laparoscopic serious game Underground by comparing
laparoscopic simulator performance for a control group and an Underground
training group. METHODS: A four-session laparoscopic basic skills course is part
of the medical master students surgical internship at the Radboud University
Medical Centre. Four cohorts, representing 107 participants, were assigned to
either the Underground group or the control group. The control group trained on
the FLS video trainer and the LapSim virtual reality simulator for four sessions.
The Underground group played Underground for three sessions followed by a
transfer session on the FLS video trainer and the LapSim. To assess the effect of
engaging in serious gameplay on performance on two validated laparoscopic
simulators, initial performance on the FLS video trainer and the LapSim was
compared between the control group (first session) and the Underground group
(fourth session). RESULTS: We chose task duration as a proxy for laparoscopic
performance. The Underground group outperformed the control group on all three
LapSim tasks: Camera navigation F(1) = 12.71, p < .01; Instrument navigation F(1)
= 8.04, p < .01; and Coordination F(1) = 6.36, p = .01. There was no significant
effect of playing Underground for performance on the FLS video trainer Peg
Transfer task, F(1) = 0.28, p = .60. CONCLUSIONS: We demonstrated skills transfer
between a serious game and validated laparoscopic simulator technology. Serious
gaming may become a valuable, cost-effective addition to the skillslab, if
transfer to the operating room can be established. Additionally, we discuss
sources of transferable skills to help explain our and previous findings.
PMID- 29349544
TI - Interpretation of motion analysis of laparoscopic instruments based on principal
component analysis in box trainer settings.
AB - BACKGROUND: Motion analysis parameters (MAPs) have been extensively validated for
assessment of minimally invasive surgical skills. However, there are
discrepancies on how specific MAPs, tasks, and skills match with each other,
reflecting that motion analysis cannot be generalized independently of the
learning outcomes of a task. Additionally, there is a lack of knowledge on the
meaning of motion analysis in terms of surgical skills, making difficult the
provision of meaningful, didactic feedback. In this study, new higher
significance MAPs (HSMAPs) are proposed, validated, and discussed for the
assessment of technical skills in box trainers, based on principal component
analysis (PCA). METHODS: Motion analysis data were collected from 25 volunteers
performing three box trainer tasks (peg grasping/PG, pattern cutting/PC, knot
suturing/KS) using the EVA tracking system. PCA was applied on 10 MAPs for each
task and hand. Principal components were trimmed to those accounting for an
explained variance > 80% to define the HSMAPs. Individual contributions of MAPs
to HSMAPs were obtained by loading analysis and varimax rotation. Construct
validity of the new HSMAPs was carried out at two levels of experience based on
number of surgeries. RESULTS: Three new HSMAPs per hand were defined for PG and
PC tasks, and two per hand for KS task. PG presented validity for HSMAPs related
to insecurity and economy of space. PC showed validity for HSMAPs related to
cutting efficacy, peripheral unawareness, and confidence. Finally, KS presented
validity for HSMAPs related with economy of space and knotting security.
CONCLUSIONS: PCA-defined HSMAPs can be used for technical skills' assessment.
Construct validation and expert knowledge can be combined to infer how
competences are acquired in box trainer tasks. These findings can be exploited to
provide residents with meaningful feedback on performance. Future works will
compare the new HSMAPs with valid scoring systems such as GOALS.
PMID- 29349545
TI - Risk of discontinuation of clopidogrel after 1 month following bare-metal stents:
a propensity-score adjusted comparison with continued administration of
clopidogrel after drug-eluting stents.
AB - In patients at high risk for bleeding undergoing percutaneous coronary
intervention (PCI) the use of bare-metal-stent (BMS) is considered an option that
allows discontinuation of clopidogrel after 4 weeks. We sought to investigate the
risk of early discontinuation of clopidogrel in patients with BMS as compared
with a 6-month course of clopidogrel after DES in patients with or without high
on-treatment platelet reactivity (HTPR). In 765 consecutive patients undergoing
PCI after loading with clopidogrel 600 mg, HTPR was tested by optical
aggregometry and defined as residual platelet reactivity > 14%. On top of aspirin
100 mg, patients received clopidogrel 75 mg for 4 weeks after BMS or 6 months
after DES. The primary endpoint was all-cause mortality or myocardial infarction
(MI) during 1 year. The 1-year incidence of death or MI was 3.5% with BMS (n =
484), 0.9% with DES and no HTPR (n = 211), and 7.1% with DES and HTPR (n = 70; p
= 0.03). Landmark analyses for the first 6 months demonstrated that the risk of
patients receiving BMS was similar as in patients receiving a DES with HTPR
during this period (2.3 vs. 2.9%) but lowest in patients receiving a DES without
HTPR (0.5%). The incidence of bleeding was similar in all three groups. These
findings did not change after propensity score adjustment for stent type. After
discontinuation of clopidogrel at 1 month, patients treated with BMS are at
higher risk for death or MI than patients treated with a DES and sufficiently
responding to clopidogrel planned for 6 months.ClinicalTrials.gov number
NCT00457236.
PMID- 29349546
TI - Understanding Who Benefits from Parenting Interventions for Children's Conduct
Problems: an Integrative Data Analysis.
AB - Parenting interventions are an effective strategy to reduce children's conduct
problems. For some families, that is, not all families benefit equally.
Individual trials tend to be underpowered and often lack variability to
differentiate between families how benefit less or more. Integrating individual
family level data across trials, we aimed to provide more conclusive results
about often presumed key family (parental education and ethnic background) and
child characteristics (problem severity, ADHD symptoms and emotional problems) as
putative moderators of parenting intervention effects. We included data from 786
families (452 intervention; 334 control) from all four trials on the Incredible
Years parenting intervention in The Netherlands (three randomized; one matched
control). Children ranged between 2 and 10 years (M = 5.79; SD = 1.66). Of the
families, 31% had a lower educational level and 29% had an ethnic minority
background. Using multilevel regression, we tested whether each of the putative
moderators affected intervention effects. Incredible Years reduced children's
conduct problems (d = - .34). There were no differential effects by families'
educational or ethnic background, or by children's level of ADHD symptoms.
Children with more severe conduct problems and those with more emotional problems
benefited more. Post hoc sensitivity analyses showed that for the two trials with
longer-term data, moderation effects disappeared at 4 or 12 months follow-up.
Often assumed moderators have some, but limited abilities to explain who benefits
from parenting interventions. This suggests the need for studying theoretically
more precise moderators in prevention research, other than relatively static
family characteristics alone.
PMID- 29349547
TI - Heterologous expression of two Aspergillus niger feruloyl esterases in
Trichoderma reesei for the production of ferulic acid from wheat bran.
AB - Feruloyl esterase (FAE)-encoding genes AnfaeA and AnfaeB were isolated from
Aspergillus niger 0913. For overexpression of the two genes in Trichoderma
reesei, constitutive and inductive expression plasmids were constructed based on
parental plasmid pAg1-H3. The constructed plasmids contained AnfaeA or AnfaeB
gene under the control of glyceraldehyde-3-phosphate dehydrogenase A gene (gpdA)
promoter (from A. nidulans) or cellobiohydrolases I (cbh I) gene promoter (from
T. reesei), and cbh I terminator from T. reesei. The target plasmids were
transferred into T. reesei D-86271 (Rut-C30) by Agrobacterium tumefaciens
mediated transformation (ATMT), respectively. A high level of feruloyl esterase
was produced by the recombinant fungal strains under solid-state fermentation,
and the cbh I promoter was more efficient than the gpdA promoter in the
expression of AnfaeA. The optimum temperatures and pH values were 50 degrees C
and 5.0 for AnFAEA, and 35 degrees C and 6.0 for AnFAEB. The maximum production
levels were 20.69 U/gsd for AnFAEA and 15.08 U/gsd for AnFAEB. The recombinant
fungal enzyme systems could release 62.9% (for AnFAEA) and 52.2% (for AnFAEB) of
total ferulic acids from de-starched wheat bran, which was higher than the 46.3%
releasing efficiency of A. niger 0913. The supplement of xylanase from T.
longibrachiatum in the enzymatic hydrolysis led to a small increment of the
ferulic acids release.
PMID- 29349548
TI - An effective surfactant-assisted hydrothermal pretreatment strategy for
bioethanol production from chili post-harvest residue by separate hydrolysis and
fermentation.
AB - Surfactants play major role in the delignification of lignocellulosic biomass.
Surfactant-assisted hydrothermal pretreatment was evaluated for chili post
harvest residue. Maximum reducing sugar yield of 0.445 g per g of dry biomass
(g/g) was obtained when surfactant PEG 6000 was used. Compositional analysis
revealed an efficient removal of lignin and hemicelluloses from the pretreated
biomass. Fermentation inhibitors such as furfural, 5-hydroxymethylfurfural and
organic acids were absent in the hydrolyzate. After pretreatment, the biomass can
be directly hydrolyzed without any neutralization, washing and drying, and the
hydrolyzate is devoid of major fermentation inhibitors. Fermentation with
Saccharomyces cerevisiae yielded 1.84% of ethanol with a fermentation efficiency
of 63.88%.
PMID- 29349549
TI - Biodegradation of Mordant orange-1 using newly isolated strain Trichoderma
harzianum RY44 and its metabolite appraisal.
AB - Herein, we systematically reported the capability of T. harzianum RY44 for
decolorization of Mordant orange-1. The fungi strains were isolated from the
Universiti Teknologi Malaysia tropical rain forest. For initial screening, the
decolorization was conducted using 50 strains of the fungi for 20 days incubation
time and the best performance was selected. Then, the decolorization capability
and fungal biomass were evaluated using different dye concentrations, namely, 0,
50, 75 and 100 ppm. Effects of the carbon sources (fructose, glucose, and
galactose), nitrogen sources (ammonium nitrate, ammonium sulfate and yeast
extract), surfactant (tween 80), aromatic compounds (benzoic acid, catechol and
salicylic acid), and pH on the decolorization efficiency were examined. This
study has found that the employed carbon sources, nitrogen sources, and aromatic
compounds strongly enhance the decolorization efficiency. In addition, increasing
the surfactant volume and pH generally decreased the decolorization efficiencies
from 19.5 to 9.0% and 81.7 to 60.5%, respectively. In the mechanism philosophy,
the present work has found that Mordant orange-1 were initially degraded by T.
harzianum RY44 to benzoic acid and finally transformed into salicylic acid.
PMID- 29349550
TI - Recombinase polymerase amplification combined with lateral flow dipstick for
equipment-free detection of Salmonella in shellfish.
AB - Salmonella is a major pathogen that causes acute foodborne outbreaks worldwide.
Seafood, particularly shellfish, is a proven source of Salmonella spp. infection
because many people prefer to eat it raw or lightly cooked. However, traditional
identification methods are too time-consuming and complex to detect contamination
of bacteria in the food chain in a timely manner, and few studies have aimed to
identify Salmonella in shellfish early in the supply chain. We herein developed a
method for rapid detection of Salmonella in shellfish based on the method of
recombinase polymerase amplification (RPA) combined with lateral flow dipstick
(LFD), which targets the invasion gene A (invA). The RPA-LFD was able to function
at 30-45 degrees C, and at the temperature of 40 degrees C, it only took 8 min
of amplification to reach the test threshold of amplicons. The established method
had both a good specificity and a sensitivity of 100 fg DNA per reaction (20 uL).
Regarding practical performance, RPA-LFD performed better than real-time PCR.
Another advantage of RPA-LFD is that it was capable of being performed without
expensive equipments. Thus, RPA-LFD has potential for further development as a
detection kit for Salmonella in shellfish and other foods under field conditions.
PMID- 29349551
TI - Medical Marijuana: Current Concepts, Pharmacological Actions of Cannabinoid
Receptor Mediated Activation, and Societal Implications.
AB - PURPOSE OF REVIEW: The purpose of the following review is to summarize the
history and current policies related to marijuana use and prevalence, basic and
clinical science pharmacological literature regarding efficacy, subpopulations of
concern, and varying policies regarding its use at present. RECENT FINDINGS: With
the increasingly widespread utilization of marijuana, there is also a growing
complexity of public health policy, regulation, and necessity to further assess
the medical indications and adverse long-term effects of marijuana use. Health
care providers as well as the general public must be prepared to become familiar
and up-to-date with medical literature, legislation, and educational material
regarding medical marijuana.
PMID- 29349552
TI - European Network of Trainees in Obstetrics and Gynaecology-ENTOG Exchange 2017:
an experience report from Slovenia outlining the different trainee situations
around Europe.
AB - PURPOSE: The European Network of Trainees in Obstetrics and Gynaecology (ENTOG)
is a non-profit, independent organisation that represents young trainees in
obstetrics and gynaecology around Europe. At present, ENTOG has 32 member
countries. The organisation was founded in 1997 and shall assure the exchange of
experiences between young physicians all over Europe. The aim is to improve the
quality of traineeship in all participating countries and consequently enhance
the standards for women's healthcare. METHODS: This article reports about the
experiences of trainees during the ENTOG Exchange 2017 in Slovenia and gives an
overview of the trainee situations in different ENTOG member countries. RESULTS:
The ENTOG exchange in Slovenia was a unique opportunity to get insights to the
Slovenian medical system. Reflecting about their training situations, the
participants found considerable differences in the training of young
gynaecologists throughout Europe. CONCLUSIONS: Working on the ENTOG goal of
raising the quality of training is still highly relevant. The ENTOG exchange is
an excellent way to build a network among trainees and stimulate their commitment
to improve women's healthcare in their home countries and beyond.
PMID- 29349553
TI - Differential JNK, p38 and ERK response to renal injury in a rat model of acute
pancreatitis in pregnancy.
AB - OBJECTIVE: The objective of this study was to determine the mechanism of acute
renal injury (ARI) in acute necrotizing pancreatitis in late pregnancy (ANPIP).
METHODS: Pregnant Sprague-Dawley rats in the third trimester were used for this
study, and an ANPIP model was induced by injecting 5% sodium taurocholate into
the biliary pancreatic duct. The rats were randomly divided into three groups:
the normal, sham-operated (SO) and acute necrotizing pancreatitis (ANP) groups.
Rats were killed at 3, 6, 12 h after the operation, and blood, pancreatic and
renal tissue samples were harvested. Differences were detected in the physiology,
pathology and cellular and molecular responses among the different groups.
RESULT: Serum amylase, lipase, urea and Cr levels were increased in rats with
ANPIP. Additionally, expression of phosphorylation p38 and JNK as well as TNF
alpha and NF-kappaB were increased in the renal tissues of rats with ANPIP. The
expression of phosphorylation ERK was decreased in the renal tissues of rats with
ANPIP. CONCLUSIONS: Mitogen-activated protein kinases may play an important role
in renal injury in rat models of ANPIP.
PMID- 29349554
TI - Comment on "Contemporary epidemiology and novel predictors of uterine rupture: a
nationwide population-based study".
PMID- 29349555
TI - Letter to the Editor: Comment on "Contemporary epidemiology and novel predictors
of uterine rupture: a nationwide population-based study".
PMID- 29349556
TI - Neuropathology correlates of cognitive assessments.
AB - BACKGROUND: Alzheimer's disease and other dementias are the fourth largest
contributors to neurological disability and the second largest contributor to
deaths from neurological disease. Described in the 1980s as 'the silent epidemic'
these disorders principally, though not exclusively, affect persons 80 years or
older, and in developed countries, this 'old old' population continues to grow.
Definitive diagnosis of the underlying cause of the neurodegenerative disease
relies on neuropathological evaluation.' AIMS: Herein, we review the sampling
methods, analysis and interpretation of both pathological and immunocytochemical
techniques in the diagnostic assessment of neurodegenerative disease. FINDINGS:
Neurodegenerative disorders are characterised by accumulation of pathologically
altered protein in the human brain, and in some cases, in the peripheral tissues.
Whilst it is suggested that a comprehensive review of the patient's clinical
history, cognition and behaviour, together with a full clinical examination and
radiological analysis, should lead to a high degree of confidence in the clinical
diagnosis, the view persists that underlying pathology can only be predicted on
clinical grounds especially in Alzheimer's disease, vascular brain injury and
diffuse Lewy body disease with only limited accuracy. CONCLUSIONS:
Neuropathological assessment of well characterised clinical cases provides
accurate data on the prevalence of neurodegenerative diseases. This will aid
future biomarker, neuroimaging studies and clinical trials focussed on population
based cohorts.
PMID- 29349557
TI - A rare ocular complication of neisseria gonorrhoeae.
AB - BACKGROUND: Spontaneous formation of subconjunctival filtering blebs is rare and
has been observed after penetrating ocular surgery, in association with
connective tissue diseases and inflammatory conditions. METHOD: We describe here
a case of a spontaneous formation of subconjunctival filtering bleb as sequelae
of gonococcal conjunctivitis in an adult patient. RESULTS: Spontaneous filtering
bleb is a rare complication of gonococcal conjunctivitis. In this case, the
patient presented with a recent history of gonococcal conjunctivitis treated with
moxifloxacin eye drops and intravenous cephalothin for a week. On the first exam,
there was superior corneal thinning with surrounding conjunctival hyperemia and
edema in the right eye, but after the patient lost the follow-up for 2 weeks, the
corneal thinning had become a pseudopterygium. After another week, we observed a
focal elevation on the superior conjunctiva that had the appearance of a bleb,
although the anterior chamber remained deep. The filtering bleb was confirmed by
ultrasound biomicroscopy examination (UBM). CONCLUSION: This case is relevant to
the clinical practice because filtering blebs should be considered as a
complication of gonococcal conjunctivitis because they pose a threat to the eye
when substantial leakage occurs.
PMID- 29349558
TI - SGLT2 Inhibitors and Mechanisms of Hypertension.
AB - PURPOSE OF REVIEW: We sought to review currently available data on the safety and
efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors in type 2 diabetes
mellitus patients with hypertension. RECENT FINDINGS: Inhibition of SGLT2 in the
renal proximal tubule results in increased urinary glucose excretion and modest
improvements of hemoglobin A1C. Treatment with any of the three currently FDA
approved SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) results
in sustained systolic and diastolic blood pressure reduction, in part via minimal
natriuresis and possible reductions in sympathetic tone. Recent randomized
clinical trials in high cardiovascular risk patients with type 2 diabetes suggest
that the unique effects of SGLT2 inhibitors on blood pressure and body weight may
translate into reduced cardiovascular events and slowed kidney disease
progression. However, concerns about volume depletion and acute kidney injury
have been raised. SGLT2 inhibitors are viable second-line glucose-lowering agents
for people with type 2 diabetes with high cardiovascular risk.
PMID- 29349560
TI - Effect of fibrillatory wave amplitude on coronary blood flow as assessed by
thrombolysis in myocardial infarction frame count in patients with atrial
fibrillation.
AB - Atrial fibrillation (AF) is the most common arrhythmia, characterized by a lack
of atrial contraction and an irregular ventricular rhythm. We assessed the effect
of fibrillatory wave amplitude on coronary blood flow in patients with AF using
the thrombolysis in myocardial infarction (TIMI) frame count. Sixty-one patients
with AF persisting for longer than 30 days were included. For controls, 61 age-
and sex-matched patients with sinus rhythm were selected. Coarse AF was defined
as any fibrillatory wave >= 1 mm and fine AF as any fibrillatory wave < 1 mm.
Mean TIMI frame count was significantly higher in patients with AF than in those
with sinus rhythm (18 +/- 4 vs 30 +/- 11, p < 0.001). Multivariate analysis
showed that AF was the only determinant of mean TIMI frame count (beta = 0.48, p
< 0.001). Among patients with AF, 32 had coarse AF and 29 had fine AF. Left
atrial volume index (54 +/- 14 vs 64 +/- 21 ml/m2, p = 0.03) was significantly
larger, and mean TIMI frame count (26 +/- 7 vs 35 +/- 12, p < 0.001) was
significantly higher in patients with fine AF than in those with coarse AF.
Multivariate analysis showed that hypertension (beta = - 0.29, p = 0.01) and a
fine fibrillatory wave (beta = 0.33, p = 0.007) were determinants of mean TIMI
frame count. Our data suggest that coronary blood flow is reduced in patients
with AF compared with those with sinus rhythm, and that a fine fibrillatory wave
is a major determinant of reduced coronary blood flow in patients with AF.
PMID- 29349561
TI - Sphenopalatine ganglion stimulation for cluster headache, results from a large,
open-label European registry.
AB - BACKGROUND: Cluster headache (CH) is a disabling primary headache disorder
characterized by severe periorbital pain. A subset of patients does not respond
to established pharmacological therapy. This study examines outcomes of a cohort
of mainly chronic CH patients treated with sphenopalatine ganglion (SPG)
stimulation. METHODS: Patients were followed in an open-label prospective study
for 12 months. Ninety-seven CH patients (88 chronic, 9 episodic) underwent trans
oral insertion of a microstimulator targeting the SPG. Patients recorded
stimulation effect prospectively for individual attacks. Frequency, use of
preventive and acute medications, headache impact (HIT-6) and quality of life
measures (SF-36v2) were monitored at clinic visits. Per protocol, frequency
responders experienced >= 50% reduction in attack frequency and acute responders
treated >= 50% of attacks. HIT-6 responders experienced an improvement >= 2.3
units and SF-36 responders >= 4 units vs. baseline. RESULTS: Eighty-five patients
(78 chronic, 7 episodic) remained implanted and were evaluated for effectiveness
at 12 months. In total, 68% of all patients were responders, 55% of chronic
patients were frequency responders and 32% of all patients were acute responders.
67% of patients using acute treatments were able to reduce the use of these by
52% and 74% of chronic patients were able to stop, reduce or remain off all
preventive medications. 59% of all patients were HIT-6 responders, 67% were SF-36
responders. CONCLUSIONS: This open-label registry corroborates that SPG
stimulation is an effective therapy for CH patients providing therapeutic
benefits and improvements in use of medication as well as headache impact and
quality of life.
PMID- 29349559
TI - A mutant HCN4 channel in a family with bradycardia, left bundle branch block, and
left ventricular noncompaction.
AB - We found that a female infant presenting with left bundle branch block and left
ventricular noncompaction carries uninvestigated gene mutations HCN4(G811E),
SCN5A(L1988R), DMD(S2384Y), and EMD(R203H). Here, we explored the possible
pathogenicity of HCN4(G811E), which results in a G811E substitution in
hyperpolarization-activated cyclic nucleotide-gated channel 4, the main subunit
of the cardiac pacemaker channel. Voltage-clamp measurements in a heterologous
expression system of HEK293T cells showed that HCN4(G811E) slightly reduced whole
cell HCN4 channel conductance, whereas it did not affect the gating kinetics,
unitary conductance, or cAMP-dependent modulation of voltage-dependence.
Immunocytochemistry and immunoblot analysis showed that the G811E mutation did
not impair the membrane trafficking of the channel subunit in the heterologous
expression system. These findings indicate that HCN4(G811E) may not be a
monogenic factor to cause the cardiac disorders.
PMID- 29349562
TI - The influence of elevated hormone levels on physiologic accumulation of 68Ga
DOTATOC.
AB - OBJECTIVE: PET/CT imaging with 68Ga-1,4,7,10-tetraazacyclododecane-N,N',N",N'''
tetraacetic acid-D-Phe1-Tyr3-octreotide (DOTATOC) is useful in patients with
neuroendocrine tumors (NETs). Functioning NETs by definition secrete abnormal
levels of hormones, causing clinical symptoms. It is known that physiologic
accumulation can be seen in some organs, but it remains unknown whether elevated
hormone levels can affect the physiologic accumulation pattern of 68Ga-DOTATOC.
We aimed to investigate the influence of higher hormone levels on physiologic
accumulation of 68Ga-DOTATOC. METHODS: A total of 167 patients with known or
suspected NET lesions were enrolled in this study. The numbers of patients with
elevations of ACTH, gastrin, insulin, and no elevation were 10, 25, 7, and 125,
respectively. We compared the maximum standardized uptake value (SUVmax) in
various organs of each group. RESULTS: In the group with elevated ACTH levels,
SUVmax in the pituitary gland, the uncinate process of the pancreas and adrenal
glands was lower than those in the group with no elevation (5.7 +/- 1.9 vs. 8.4
+/- 3.1, P = 0.015; 4.7 +/- 3.5 vs. 6.4 +/- 2.8, P = 0.037; 10.8 +/- 4.8 vs. 13.9
+/- 4.7, P = 0.020, respectively). There were no differences in physiologic
uptake of 68Ga-DOTATOC in the thyroid gland, the pancreatic body, the liver, the
spleen, the bowel, or the kidney. CONCLUSIONS: In NET patients with elevated ACTH
levels, physiologic uptake of 68Ga-DOTATOC in the pituitary gland, the uncinate
process of the pancreas and adrenal glands was significantly decreased. Other
organs were unaffected.
PMID- 29349564
TI - Retraction Note to: Factors associated with post-stroke depression and fatigue:
lesion location and coping styles.
AB - The Editors-in-Chief are retracting the original article because it shows
significant overlap with an article previously published by the authors [1]. All
authors agree to this retraction.
PMID- 29349565
TI - Description of Alteromonas abrolhosensis sp. nov., isolated from sea water of
Abrolhos Bank, Brazil.
AB - Two Gram-negative, motile, aerobic bacteria isolated from waters of the Abrolhos
Bank were classified through a whole genome-based taxonomy. Strains PEL67ET and
PEL68C shared 99% 16S rRNA and dnaK sequence identity with Alteromonas marina SW
47T and Alteromonas macleodii ATCC 27126T. In silico DNA-DNA Hybridization, i.e.
genome-to-genome distance (GGD), average amino acid identity (AAI) and average
nucleotide identity (ANI) showed that PEL67ET and PEL68C had identity values
between 33-36, 86-88 and 83-84%, and 85-86 and 83%, respectively, towards their
close neighbors A. macleodii ATCC 27126T and A. marina SW-47T. The DNA G + C
contents of PEL67ET and PEL68C were 44.5%. The phenotypic features that
differentiate PEL67ET and PEL68C strains from their close neighbors were
assimilation of galactose and activity of phosphatase, and lack of mannitol,
maltose, acetate, xylose and glycerol assimilation and lack of lipase, alpha and
beta-glucosidase activity. The new species Alteromonas abrolhosensis is proposed.
The type strain is PEL67ET (= CBAS 610T = CAIM 1925T).
PMID- 29349566
TI - Performance Improvement in Head and Neck Cancer.
AB - Performance improvement requires establishing a platform to set benchmarks and
monitor the quality of care provided through quality indicators and metrics. This
has long been recognized as critical to overall quality improvement and more
recently, has become federally mandated. Here, we review recent studies
evaluating performance in head and neck cancer care, from those spanning all
phases of head and neck cancer care to others focused on head and neck surgical
performance, including both national and departmental/institutional efforts.
PMID- 29349567
TI - HBeAg induces the expression of macrophage miR-155 to accelerate liver injury via
promoting production of inflammatory cytokines.
AB - Activation of Kupffer cells (KCs) induced that inflammatory cytokine production
plays a central role in the pathogenesis of HBV infection. The previous studies
from our and other laboratory demonstrated miRNAs can regulate TLR-inducing
inflammatory responses to macrophage. However, the involvement of miRNAs in HBV
associated antigen-induced macrophage activation is still not thoroughly
understood. Here, we evaluated the effects and mechanisms of miR-155 in HBV
associated antigen-induced macrophage activation. First, co-culture assay of
HepG2 or HepG2.2.15 cells and RAW264.7 macrophages showed that HepG2.2.15 cells
could significantly promote macrophages to produce inflammatory cytokines.
Furthermore, we, respectively, stimulated RAW264.7 macrophages, mouse primary
peritoneal macrophages, or healthy human peripheral blood monocytes with HBV
associated antigens, including HBcAg, HBeAg, and HBsAg, and found that only HBeAg
could steadily enhance the production of inflammatory cytokines in these cells.
Subsequently, miRNAs sequencing presented the up- or down-regulated expression of
multiple miRNAs in HBeAg-stimulated RAW264.7 cells. In addition, we verified the
expression of miR-155 and its precursors BIC gene with q-PCR in the system of co
culture or HBeAg-stimulated macrophages. Meanwhile, the increased miR-155
expression was positively correlation with serum ALT, AST, and HBeAg levels in
AHB patients. Although MAPK, PI3K, and NF-kappaB signal pathways were all
activated during HBeAg treatment, only PI3K and NF-kappaB pathways were involved
in miR-155 expression induced by HBeAg stimulation. Consistently, miR-155 over
expression inhibited production of inflammatory cytokines, which could be
reversed by knocking down miR-155. Moreover, we demonstrated that miR-155
regulated HBeAg-induced cytokine production by targeting BCL-6, SHIP-1, and SOCS
1. In conclusion, our data revealed that HBeAg augments the expression of miR-155
in macrophages via PI3K and NF-kappaB signal pathway and the increased miR-155
promotes HBeAg-induced inflammatory cytokine production by inhibiting the
expression of BCL-6, SHIP-1, and SOCS-1.
PMID- 29349568
TI - Class III bacteriocin Helveticin-M causes sublethal damage on target cells
through impairment of cell wall and membrane.
AB - Helveticin-M, a novel Class III bacteriocin produced by Lactobacillus crispatus
exhibited an antimicrobial activity against Staphylococcus aureus, S.
saprophyticus, and Enterobacter cloacae. To understand how Helveticin-M injured
target cells, Helveticin-M was cloned and heterologously expressed in Escherichia
coli. Subsequently, the cell wall organization and cell membrane integrity of
target cells were determined. The mechanism of cellular damage differed according
to bacterial species. Based on morphology analysis, Helveticin-M disrupted the
cell wall of Gram-positive bacteria and disorganized the outer membrane of Gram
negative bacteria, therefore, altering surface structure. Helveticin-M also
disrupted the inner membrane, as confirmed by leakage of intracellular ATP from
cells and depolarization of membrane potential of target bacteria. Based on cell
population analysis, Helveticin-M treatment caused the increase of cell membrane
permeability, but the cytosolic enzymes were not influenced, indicating that it
was the sublethal injury. Therefore, the mode of Helveticin-M action is
bacteriostatic rather than bactericidal.
PMID- 29349569
TI - xylA and xylB overexpression as a successful strategy for improving xylose
utilization and poly-3-hydroxybutyrate production in Burkholderia sacchari.
AB - Despite the versatility and many advantages of polyhydroxyalkanoates as petroleum
based plastic substitutes, their higher production cost compared to petroleum
based polymers has historically limited their large-scale production. One
appealing approach to reducing production costs is to employ less expensive,
renewable feedstocks. Xylose, for example is an abundant and inexpensive carbon
source derived from hemicellulosic residues abundant in agro-industrial waste
(sugarcane bagasse hemicellulosic hydrolysates). In this work, the production of
poly-3-hydroxybutyrate P(3HB) from xylose was studied to develop technologies for
conversion of agro-industrial waste into high-value chemicals and biopolymers.
Specifically, this work elucidates the organization of the xylose assimilation
operon of Burkholderia sacchari, a non-model bacterium with high capacity for
P(3HB) accumulation. Overexpression of endogenous xylose isomerase and
xylulokinase genes was successfully assessed, improving both specific growth rate
and P(3HB) production. Compared to control strain (harboring pBBR1MCS-2), xylose
utilization in the engineered strain was substantially improved with 25% increase
in specific growth rate, 34% increase in P(3HB) production, and the highest
P(3HB) yield from xylose reported to date for B. sacchari (YP3HB/Xil = 0.35 g/g).
This study highlights that xylA and xylB overexpression is an effective strategy
to improve xylose utilization and P(3HB) production in B. sacchari.
PMID- 29349570
TI - Assessment of ten density functionals through the use of local hyper-softness to
get insights about the catalytic activity : Iron-based organometallic compounds
for ethylene polymerization as testing molecules.
AB - Ten functionals were used to assess their capability to compute a local
reactivity descriptor coming from the Conceptual Density Functional Theory on a
group of iron-based organometallic compounds that have been synthesized by
Zohuri, G.H. et al. in 2010; these compounds bear the following substituent
groups: H-, O2N- and CH3O- at the para position of the pyridine ring and their
catalytic activities were experimentally measured by these authors. The present
work involved a theoretical analysis applied on the aforementioned iron-based
compounds thus leading to suggest a new 2,6-bis(imino)pyridine catalyst based on
iron(II) bearing a fluorine atom whose possible catalytic activity is suggested
to be near the catalytic activity of the complex bearing a hydrogen atom as a
substituent group by means of the so called local hyper-softness (LHS) thus
opening a chance to estimate a possible value of catalytic activity for a new
catalyst that has not been synthesized yet without simulating the entire process
of ethylene polymerization. Since Conceptual DFT is not a predictive theory, but
rather interpretative, an analysis of the used reactivity descriptor and its
dependence upon the level of theory was carried in the present work, thus
revealing that care should be taken when DFT calculations are used for these
purposes.
PMID- 29349571
TI - Fluoroscopy-free ultrasonography-guided percutaneous nephrolithotomy in pediatric
patients: a single-center experience.
AB - OBJECTIVES: To present the safety and efficacy of fluoroscopy-free ultrasound
guided PCNL for the treatment of renal calculi in pediatric patients of all ages.
METHODS: 30 children with mean age of 5 years (6 months-12 years) underwent
totally ultrasound-guided PCNL from March 2013 to August 2016. The pyelocalyceal
system was punctured in prone position using only ultrasonography guidance, and
the tract was dilated using a single shot dilation technique. No fluoroscopy was
used during any of the stages of renal access. The procedure was performed using
adult-sized instruments. RESULTS: The mean stone size was 27.1 +/- 8.7 mm. Mean
access time was 4.3 +/- 2 min. Mean nephroscopic time was 34.6 +/- 15.2 min. Mean
hospital stay of patients was 3 days (range 2-5). 21 patients were stone-free
after the procedure (70% success rate). Only four patients out of 30 experienced
postoperative complications. CONCLUSIONS: The results of this study showed that
fluoroscopic-free ultrasound-guided PCNL in pediatric patients of all ages is
safe, highly efficient, and minimizes potential radiation exposure risks
associated with the procedure.
PMID- 29349572
TI - A prospective study evaluating indirect MRI-signs for the prediction of
extraprostatic disease in patients with prostate cancer: tumor volume, tumor
contact length and tumor apparent diffusion coefficient.
AB - OBJECTIVE: The aim of this study was to evaluate three indirect MRI signs for
predicting extraprostatic disease in patients referred to radical prostatectomy:
index tumor volume (MTV), apparent diffusion coefficient (ADC) and tumor contact
length (TCL). MATERIALS AND METHODS: This prospective study included 183 patients
with biopsy proven prostate cancer. In all patients the MTV (ml), ADC (* 10-5
mm2/s) and TCL (mm) of the index tumor were registered at the preoperative MRI.
Whole-mounted microscopical examination classified each patient as having either
localized- or extraprostatic disease. The Youden index was used to identify the
optimal cut-off values for predicting extraprostatic disease. Univariate
regression analyses were conducted to estimate the odds ratio (OR) with 95%
confidence intervals (CI). Results were stratified upon zonal location of the
index tumor. RESULTS: Extraprostatic disease was identified in 103 (56%)
patients. The risk of extraprostatic disease was nine times higher in peripheral
zone tumors with ADC <= 89 (OR 9.1, 95% CI 4.2-19.6), five times higher in MTV >=
0.9 ml (OR 5.5, 95% CI 2.6-11.4) and five times higher in case of TCL >= 14 mm
(OR 4.9, 95% CI 2.3-10.2). None of the indirect MRI signs could predict
extraprostatic disease for transition zone tumors. CONCLUSION: The MTV, ADC and
TCL are all significant predictors of extraprostatic disease for peripheral zone
tumors, while none of the indirect signs were useful for transition zone tumors.
PMID- 29349573
TI - Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Elevates Stimulus
Evoked Release of Dopamine in Freely-Moving Rats.
AB - Neurotrophic factors (NTFs) hold potential as disease-modifying therapies for
neurodegenerative disorders like Parkinson's disease. Glial cell line-derived
neurotrophic factor (GDNF), cerebral dopamine neurotrophic factor (CDNF), and
mesencephalic astrocyte-derived neurotrophic factor (MANF) have shown
neuroprotective and restorative effects on nigral dopaminergic neurons in various
animal models of Parkinson's disease. To date, however, their effects on brain
neurochemistry have not been compared using in vivo microdialysis. We measured
extracellular concentration of dopamine and activity of dopamine neurochemistry
regulating enzymes in the nigrostriatal system of rat brain. NTFs were
unilaterally injected into the striatum of intact Wistar rats. Brain
microdialysis experiments were performed 1 and 3 weeks later in freely-moving
animals. One week after the treatment, we observed enhanced stimulus-evoked
release of dopamine in the striatum of MANF-treated rats, but not in rats treated
with GDNF or CDNF. MANF also increased dopamine turnover. Although GDNF did not
affect the extracellular level of dopamine, we found significantly elevated
tyrosine hydroxylase (TH) and catechol-O-methyltransferase (COMT) activity and
decreased monoamine oxidase A (MAO-A) activity in striatal tissue samples 1 week
after GDNF injection. The results show that GDNF, CDNF, and MANF have divergent
effects on dopaminergic neurotransmission, as well as on dopamine synthetizing
and metabolizing enzymes. Although the cellular mechanisms remain to be
clarified, knowing the biological effects of exogenously administrated NTFs in
intact brain is an important step towards developing novel neurotrophic
treatments for degenerative brain diseases.
PMID- 29349574
TI - Pacific Ciguatoxin Induces Excitotoxicity and Neurodegeneration in the Motor
Cortex Via Caspase 3 Activation: Implication for Irreversible Motor Deficit.
AB - Consumption of fish containing ciguatera toxins or ciguatoxins (CTXs) causes
ciguatera fish poisoning (CFP). In some patients, CFP recurrence occurs even
years after exposure related to CTXs accumulation. Pacific CTX-1 (P-CTX-1) is one
of the most potent natural substances known that causes predominantly
neurological symptoms in patients; however, the underlying pathogenies of CFP
remain unknown. Using clinically relevant neurobehavioral tests and
electromyography (EMG) to assess effects of P-CTX-1 during the 4 months after
exposure, recurrent motor strength deficit occurred in mice exposed to P-CTX-1.
We detected irreversible motor strength deficits accompanied by reduced EMG
activity, demyelination, and slowing of motor nerve conduction, whereas control
unexposed mice fully recovered in 1 month after peripheral nerve injury. Finally,
to uncover the mechanism underlying CFP, we detected reduction of spontaneous
firing rate of motor cortical neurons even 6 months after exposure and increased
number of glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes.
Increased numbers of motor cortical neuron apoptosis were detected by dUTP
digoxigenin nick end labeling assay along with activation of caspase 3. Taken
together, our study demonstrates that persistence of P-CTX-1 in the nervous
system induces irreversible motor deficit that correlates well with
excitotoxicity and neurodegeneration detected in the motor cortical neurons.
PMID- 29349575
TI - Parkin in Parkinson's Disease and Cancer: a Double-Edged Sword.
AB - Parkin for more than a decade has been portrayed as a neuroprotector gene is now
increasingly emerging as a multifaceted gene that can exert entirely opposite
effects i.e., both cell proliferation and apoptosis. Parkinson's disease, a
neurological disease, progresses due to excess in cell death, while, in case of
cancer, cell death normally fails to occur. Parkin, an E3 ubiquitin ligase, was
first identified as a gene implicated in autosomal recessive juvenile
Parkinsonism, but several evidences indicate that Parkin is a tumor suppressor
gene, involved in a variety of cancers. It is hard to imagine that two entirely
different classes of disease, like cancer and Parkinson's disease, can converge
at a critical point attributable to a single gene, Parkin. This mysterious and
hidden connection may prove a boon in disguise and has raised hopes that studying
the biology of one disease may help to identify novel targets of therapy for the
other. In this Parkinson's disease-cancer story, if the detail of Parkin pathway
is unraveled and gaps in the storyline are properly filled up, we may end getting
an entirely new therapeutic option. This review mainly highlights the recent
literature which suggests how Parkin gene regulates the various hallmarks of both
the Parkinson's disease and cancer.
PMID- 29349576
TI - Prep1 Deficiency Affects Olfactory Perception and Feeding Behavior by Impairing
BDNF-TrkB Mediated Neurotrophic Signaling.
AB - Prep1 is a homeodomain transcription factor which has an important role in
hindbrain development. Prep1 expression is also kept in adult mouse brain and in
particular within the olfactory bulbs. Moreover, many Prep1 neurons co-localize
with Calbindin-positive periglomerular interneurons in olfactory glomerular
layer. However, Prep1 function in this brain region is still unknown. In this
study, we show that Prep1 hypomorphic heterozygous (Prep1i/+) mice express low
levels of protein and feature a 30% reduction of olfactory bulb area, compared to
WT mice. In addition, Prep1i/+ mice olfactory bulb histological analysis
indicated a 20% lower cytochrome C oxidase activity within the glomerular layer,
accompanied by a reduced number of periglomerular interneurons, compared to the
WT littermates. Consistently, olfactory perception test highlighted that Prep1
hypomorphic heterozygous mice display a scant ability to distinguish odors, which
significantly impacts on feeding behavior, as Prep1i/+ mice revealed a reduced
preference for high-fat food. Analysis of BDNF signaling, which represents the
main molecular mediator of olfactory plasticity, showed that Prep1i/+ mouse
olfactory bulbs feature a 30% reduction of TrkB receptor levels and a decreased
activation of ERK1/2. Similarly, overexpression of Prep1 in mouse neuronal cells
(N2A) caused an increase of TrkB expression levels, BDNF-induced ERK
phosphorylation, and cell viability, compared to control cells. We conclude that
Prep1 deficiency alters olfactory morpho-functional integrity and olfaction
mediated eating behavior by affecting BDNF-TrkB signaling. Prep1 could,
therefore, play a crucial role in behavioral dysfunctions associated to impaired
responsiveness to BDNF.
PMID- 29349578
TI - In Situ Tissue Labeling of Cerebral Amyloid Using HIV-Related Tat Peptide.
AB - Delivering peptide-based drugs to the brain is a major challenge because of the
existence of the blood-brain barrier (BBB). To overcome this problem, cell
penetrating peptides derived from proteins that are able to cross biological
membranes have been used as cell-permeable and brain-penetrant compounds. An
example is the transactivator of transcription protein transduction domain (Tat)
of the human immunodeficiency virus. The basic domain of Tat is formed of
arginine and lysine amino acid residues. Tat has been used as brain-penetrant
carrier also in therapies for Alzheimer disease (AD), the most common form of
dementia characterized by extracellular cerebral deposits of amyloid made up of
Abeta peptide. The aim of our study was to assess whether Tat bind to amyloid
deposits of AD and other amyloidoses. An in situ labeling using biotinylated Tat
48-57 peptide was employed in the brain tissue with amyloid deposits made up of
Abeta (patients with AD and transgenic AD mice), of prion protein (patients with
Gerstmann-Straussler-Scheinker disease), and other amyloidosis, processed by
different fixations and pretreatments of histological sections. Our results
showed that Tat peptide binds amyloid deposits made up of Abeta, PrP, and
immunoglobulin lambda chains in the brain and other tissues processed by
alcoholic fixatives but not in formalin-fixed tissue. The fact that biotinylated
Tat peptide stains amyloid of different biochemical composition and the specific
charge characteristics of the molecules suggests that Tat may bind to heparan
sulfate glicosaminoglicans, that are present in amyloid deposits. Inhibition of
the binding by Tat pre-incubation with protamine reinforces this hypothesis.
Binding of Tat to amyloid deposits should be kept in mind in interpreting the
results of studies employing this molecule as brain-penetrating compound for the
treatment of cerebral amyloidoses. Our results also suggest that Tat may be
helpful for the analysis of the mechanisms of amyloidogenesis, and in particular,
the interactions between specific amyloid peptides and glicosaminoglicans.
PMID- 29349577
TI - Combination Therapy with Sulfasalazine and Valproic Acid Promotes Human
Glioblastoma Cell Death Through Imbalance of the Intracellular Oxidative
Response.
AB - Glioblastoma (GBM) is the most common and aggressive malignant primary brain
tumor and still lacks effective therapeutic strategies. It has already been shown
that old drugs like sulfasalazine (SAS) and valproic acid (VPA) present
antitumoral activities in glioma cell lines. SAS has also been associated with a
decrease of intracellular glutathione (GSH) levels through a potent inhibition of
xc- glutamate/cystine exchanger leading to an antioxidant deprotection. In the
same way, VPA was recently identified as a histone deacetylase (HDAT) inhibitor
capable of activating tumor suppression genes. As both drugs are widely used in
clinical practice and their profile of adverse effects is well known, the aim of
our study was to investigate the effects of the combined treatment with SAS and
VPA in GBM cell lines. We observed that both drugs were able to reduce cell
viability in a dose-dependent manner and the combined treatment potentiated these
effects. Combined treatment also increased cell death and inhibited proliferation
of GBM cells, while having no effect on human and rat cultured astrocytes. Also,
we observed high protein expression of the catalytic subunit of xc- in all the
examined GBM cell lines, and treatment with SAS blocked its activity and
decreased intracellular GSH levels. Noteworthy, SAS but not VPA was also able to
reduce the [14C]-ascorbate uptake. Together, these data indicate that SAS and VPA
exhibit a substantial effect on GBM cell's death related to an intracellular
oxidative response imbalance, making this combination of drugs a promising
therapeutic strategy.
PMID- 29349579
TI - Malaria infectivity of xanthurenic acid-deficient anopheline mosquitoes produced
by TALEN-mediated targeted mutagenesis.
AB - Anopheline mosquitoes are major vectors of malaria parasites. When the
gametocytes of the malaria parasite are transferred from a vertebrate to
mosquitoes, they differentiate into gametes, and are fertilized in the midguts of
mosquitoes. Xanthurenic acid (XA), a waste product of the ommochrome synthesis
pathway, has been shown to induce exflagellation during microgametogenesis in
vitro; however, it currently remains unclear whether endogenous XA affects the
infectivity of anopheline mosquitoes to malaria parasites in vivo due to the lack
of appropriate experimental systems such as a XA-deficient line. In the present
study, we produced a XA-deficient line in Anopheles stephensi using transcription
activator-like effector nuclease (TALEN)-mediated gene targeting (knockout) of
the kynurenine 3-monooxygenase (kmo) gene, which encodes an enzyme that
participates in the ommochrome synthesis pathway. The knockout of kmo resulted in
the absence of XA, and oocyst formation was inhibited in the midguts of these XA
deficient mosquitoes, which, in turn, reduced sporozoite numbers in their
salivary glands. These results suggest that endogenous XA stimulates
exflagellation, and enhances the infectivity of anopheline mosquitoes to malaria
parasites in vivo. The XA-deficient line of the anopheline mosquito provides a
useful system for analyzing and understanding the associated factors of malaria
gametogenesis in the mosquito midgut.
PMID- 29349580
TI - Perianesthetic Management of Laparoscopic Kidney Surgery.
AB - PURPOSE OF REVIEW: Laparoscopic kidney surgery is commonly used for living donor,
partial, and total tumor nephrectomy. The successful emergence of laparoscopic
technique was justified by the many benefits offered such as reduced blood loss,
tissue trauma, pain, and hospital stay. However, this comes at the expense of
physiologic changes and complications secondary to pneumoperitoneum, surgical
technique, and patient positioning with significant challenges in anesthetic
management. RECENT FINDINGS: A variety of laparoscopic approaches
(transperitoneal, retroperitoneal, hand-assisted, robotic) are used with some
having advantages over others. The kidneys are particularly sensitive to
hemodynamic changes and pneumoperitoneum. Controversies in perioperative fluid
administration exist. New modalities for postoperative pain control have been
suggested. Laparoscopic kidney surgery is associated with multiple physiologic
changes and adverse events but offers advantages of reduced postoperative pain,
faster recovery, and shorter hospital stay. Understanding these physiologic
changes and related anesthetic considerations is key for safe patient outcome.
PMID- 29349581
TI - Quantitative assessment of thyroid gland elasticity with shear-wave elastography
in pediatric patients with Hashimoto's thyroiditis.
AB - OBJECTIVE: Hashimoto's thyroiditis is the most common autoimmune thyroid disorder
in the pediatric age range. Measurement of thyroid gland size is an essential
component in evaluation and follow-up of thyroid pathologies. Along with size,
tissue elasticity is becoming a more commonly used parameter in evaluation of
parenchyma in inflammatory diseases. The aim of the current study was to assess
thyroid parenchyma elasticity by shear-wave elastography in pediatric patients
with Hashimoto's thyroiditis; and compare the elasticity values to a normal
control group. MATERIALS AND METHODS: In this study; thyroid glands of 59
patients with a diagnosis of Hashimoto's thyroiditis based on ultrasonographic
and biochemical features, and 26 healthy volunteers without autoimmune thyroid
disease and thyroid function disorders, were evaluated with shear-wave
elastography. Patients with Hashimoto thyroiditis were further subdivided into
three categories based on gray-scale ultrasonography findings as focal
thyroiditis (grade 1), diffuse thyroiditis (grade 2), and fibrotic thyroid gland
(grade 3). RESULTS: Patients with Hashimoto's thyroiditis (n = 59) had
significantly higher elasticity values (14. 9 kPa; IQR 12.9-17.8 kPa) than
control subjects (10.6 kPa; IQR 9.0-11.3 kPa) (p < 0.001). Of the 59 patients
with Hashimoto's thyroiditis, 23 patients had focal thyroiditis involving less
than 50% of the gland categorized as grade 1, 24 patients had diffuse involvement
of the thyroid gland categorized as grade 2, and 12 patients had marked
hyperechoic septations and pseudonodular appearance categorized as grade 3 on
gray-scale ultrasound. Based on elastography, grade 3 patients had significantly
higher elasticity values (19.7 kPa; IQR 17.8-21.5 kPa) than patients with grade 2
(15.5 kPa; IQR 14.5-17.8 kPa) and grade 1 thyroiditis (12.8 kPa; IQR 11.9-13.1
kPa) (p < 0.05). Patients with grade 2 thyroiditis had significantly higher
elasticity values than those with grade 1 thyroiditis (p < 0.05). CONCLUSION:
Gray-scale ultrasound findings of heterogeneous echotexture and hypoechoic
echogenicity reflect a longer duration of inflammation and may not be found in
the initial stages of thyroiditis. Our results indicate that shear-wave
elastography could be used to evaluate the degree of fibrosis in Hashimoto's
thyroiditis.
PMID- 29349582
TI - Can we evaluate the levator ani after Kegel exercise in women with pelvic organ
prolapse by transperineal elastography? A preliminary study.
AB - OBJECTIVES: The aim of this study was to evaluate the stiffness variation of the
levator ani in patients with stage I/II pelvic organ prolapse (POP) before and
after Kegel exercises by transperineal elastography. METHODS: A total of 20
patients who were diagnosed with staged I/II POP underwent conventional
transperineal ultrasound and elastography. For each patient, the levator ani was
located and evaluated in the state of Valsalva. After Kegel exercises for 12
weeks, transperineal ultrasound and elastography were repeated. The elasticity
images were assessed using a four-point scale scoring system. RESULTS: Of the 20
cases, four had an elastography score of 1, 14 had a score of 2, two had a score
of 3, and no cases had a score of 4 in the levator ani before Kegel exercises.
After Kegel exercises, one had an elastography score of 1, two had a score of 2,
15 had a score of 3, and two cases had a score of 4. The mean elastography score
was statistically significantly higher for the levator ani after Kegel exercises
(2.90 +/- 0.48) than for the baseline score (1.90 +/- 0.29) (p = 0.025).
CONCLUSIONS: Transperineal elastography was an effective and useful tool in the
evaluation of the levator ani in patients with POP-Q stage I/II before and after
Kegel exercises.
PMID- 29349583
TI - Enhanced production of phenolic acids in cell suspension culture of Salvia
leriifolia Benth. using growth regulators and sucrose.
AB - Salvia leriifolia Benth. (Lamiaceae) is an endangered medicinal plant with
hypoglycemic, anti-inflammatory and analgesic properties. Many of the beneficial
effects of Salvia spp. are attributed to the phenolic compounds. In the present
study, an efficient procedure has been developed for establishment of cell
suspension culture of S. leriifolia as a strategy to obtain an in vitro phenolic
acids producing cell line for the first time. The effect of growth regulators and
various concentrations of sucrose have been analyzed, to optimize biomass growth
and phenolic acids production. The callus used for this purpose was obtained from
leaves of 15-day-old in vitro seedlings, on Murashige and Skoog (MS) basal medium
supplemented with different hormone balances including benzylaminopurine (BAP)
and indole butyric acid (IBA); 2,4-dichlorophenoxyacetic acid (2,4-D) and kinetin
(KIN); naphthaleneacetic acid (NAA) and BAP. Modified MS medium supplemented with
5 mg/L BAP and 5 mg/L NAA was the optimal condition for callus formation with the
highest induction rate (100%), the best callus growth and the highest phenolic
acids content. No callus induction was observed in combinations of IBA and BAP.
Cell suspension cultures were established by transferring 0.5 g of callus to 30
mL liquid MS medium supplemented with 5 mg/L BAP and 5 mg/L NAA. Dynamics of
phenolic acids production has been investigated during the growth cycle of the
suspension cultures. The maximum content of caffeic acid and salvianolic acid B
were observed on the 15th day of the cultivation cycle while the highest amount
of rosmarinic acid was observed on the first day. In response to various sucrose
concentrations, cell cultures with 40 g/L sucrose not only produced the highest
dry biomass but also the highest induction of caffeic acid and salvianolic acid
B. The highest amount of rosmarinic acid was observed in media containing 50 g/L
sucrose. These prepared cell suspension cultures provided a useful system for
further enhanced production of phenolic acids at a large scale.
PMID- 29349584
TI - [Percutaneous endoscopic gastrostomy in geriatrics : Indications, technique and
complications].
AB - The technique of percutaneous endoscopic gastrostomy (PEG) was introduced in 1979
as a semi-invasive approach for children with the need for a gastric fistula in
order to avoid an operative intervention. The suture pull-through method was
rapidly established and is now omnipresent. Because scientific evidence is
broadly missing, there is some uncertainty about the indications in geriatric
medicine. Guidelines do not recommend the insertion of a PEG in patients with
severe dementia and malnutrition. Tube feeding is mainly recommended as a
temporary method for patients who cannot take oral nutrition for more than 3 days
or for whom the energy intake for more than 10 days presumably covers less than
50% of their needs, assuming that the overall prognosis is reasonable. Insertion
of a PEG is only recommended if artificial nutrition is expected to be necessary
for more than 3-4 weeks or if a nasogastric tube is not tolerated.
PMID- 29349585
TI - Molecularly Imprinted Core-Shell CdSe@SiO2/CDs as a Ratiometric Fluorescent Probe
for 4-Nitrophenol Sensing.
AB - 4-Nitrophenol (4-NP) is a priority pollutant in water and is both carcinogenic
and genotoxic to humans and wildlife even at very low concentrations. Thus, we
herein fabricated a novel molecularly imprinted core-shell nanohybrid as a
ratiometric fluorescent sensor for the highly sensitive and selective detection
of 4-NP. This sensor was functioned by the transfer of fluorescence resonance
energy between photoluminescent carbon dots (CDs) and 4-NP. This sensor was
synthesized by linking organosilane-functionalized CDs to silica-coated CdSe
quantum dots (CdSe@SiO2) via Si-O bonds. The nanohybrids were further modified by
anchoring a molecularly imprinted polymer (MIP) layer on the ratiometric
fluorescent sensor through a facile sol-gel polymerization method. The
morphology, chemical structure, and optical properties of the resulting
molecularly imprinted dual-emission fluorescent probe were characterized by
transmission electron microscopy and spectroscopic analysis. The probe was then
applied in the detection of 4-NP and exhibited good linearity between 0.051 and
13.7 MUg/mL, in addition to a low detection limit of 0.026 MUg/mL. Furthermore,
the simplicity, reliability, high selectivity, and high sensitivity of the
developed sensor demonstrate that the combination of MIPs and ratiometric
fluorescence allows the preparation of excellent fluorescent sensors for the
detection of trace or ultra-trace analytes.
PMID- 29349586
TI - Cancer incidence among children and young adults who have undergone x-ray guided
cardiac catheterization procedures.
AB - Children and young adults with heart disease appear to be at increased risk of
developing cancer, although the reasons for this are unclear. A cohort of 11,270
individuals, who underwent cardiac catheterizations while aged <= 22 years in the
UK, was established from hospital records. Radiation doses from cardiac
catheterizations and CT scans were estimated. The cohort was matched with the NHS
Central Register and NHS Transplant Registry to determine cancer incidence and
transplantation status. Standardized incidence ratios (SIR) with associated
confidence intervals (CI) were calculated. The excess relative risk (ERR) of
lymphohaematopoietic neoplasia was also calculated using Poisson regression. The
SIR was raised for all malignancies (2.32, 95% CI 1.65, 3.17), lymphoma (8.34,
95% CI 5.22, 12.61) and leukaemia (2.11, 95% CI 0.82, 4.42). After censoring
transplant recipients, post-transplant, the SIR was reduced to 0.90 (95% CI 0.49,
1.49) for all malignancies. All lymphomas developed post-transplant. The SIR for
all malignancies developing 5 years from the first cardiac catheterization (2
years for leukaemia/lymphoma) remained raised (3.01, 95% CI 2.09, 4.19) but was
again reduced after censoring transplant recipients (0.98, 95% CI 0.48, 1.77).
The ERR per mGy bone marrow dose for lymphohaematopoietic neoplasia was reduced
from 0.541 (95% CI 0.104, 1.807) to 0.018 (95% CI - 0.002, 0.096) where
transplantation status was accounted for as a time-dependent background risk
factor. In conclusion, transplantation appears to be a large contributor to
elevated cancer rates in this patient group. This is likely to be mainly due to
associated immunosuppression, however, radiation exposure may also be a
contributing factor.
PMID- 29349587
TI - The Danish Medical Birth Register.
AB - The Danish Medical Birth Register was established in 1973. It is a key component
of the Danish health information system. The register enables monitoring of the
health of pregnant women and their offspring, it provides data for quality
assessment of the perinatal care in Denmark, and it is used extensively for
research. The register underwent major changes in construction and content in
1997, and new variables have been added during the last 20 years. The aim was to
provide an updated description of the register focusing on structure, content,
and coverage since 1997. The register includes data on all births in Denmark and
comprises primarily of data from the Danish National Patient Registry
supplemented with forms on home deliveries and stillbirths. It contains
information on maternal age provided by the Civil Registration System.
Information on pre-pregnancy body mass index and smoking in first trimester is
collected in early pregnancy (first antenatal visit). The individual-level data
can be linked to other Danish health registers such as the National Patient
Registry and the Danish National Prescription Registry. The register informs
several other registers/databases such as the Danish Twin Registry and the Danish
Fetal Medicine Database. Aggregated data can be publicly accessed on the Danish
Health Data Authority web page ( www.esundhed.dk/sundhedsregistre/MFR ).
Researchers can obtain access to individual-level pseudo-anonymised data via
servers at Statistics Denmark and the Danish Health Data Authority.
PMID- 29349588
TI - Amphiregulin enhances cardiac fibrosis and aggravates cardiac dysfunction in mice
with experimental myocardial infarction partly through activating EGFR-dependent
pathway.
AB - Cardiac fibrosis (CF), a main process of ventricular remodeling after myocardial
infarction (MI), plays a crucial role in the pathogenesis of heart failure (HF)
post-MI. It is known that amphiregulin (AR) is involved in fibrosis of several
organs. However, the expression of AR and its role post-MI are yet to be
determined. This study aimed to investigate the impact of AR on CF post-MI and
related mechanisms. Significantly upregulated AR expression was evidenced in the
infarct border zone of MI mice in vivo and the AR secretion was enhanced in
macrophages, but not in cardiac fibroblasts. In vitro, treatment with AR
increased cardiac fibroblast migration, proliferation and collagen synthesis, and
upregulated the expression of epidermal growth factor receptor (EGFR) and the
downstream genes such as Akt, ERK1/2 and Samd2/3 on cardiac fibroblasts. All
these effects could be abrogated by pretreatment with a specific EGFR inhibitor.
To verify the functions of AR in MI hearts, lentivirus-AR-shRNA and negative
control vectors were delivered into the infarct border zone. After 28 days, knock
down of AR increased the survival rate and improved cardiac function, while
decreasing the extent of myocardial fibrosis of MI mice. Moreover, EGFR and the
downstream genes were significantly downregulated in lentivirus-AR-shRNA treated
MI mice. Our results thus indicate that AR plays an important role in promoting
CF after MI partly though activating the EGFR pathway. Targeting AR might be a
novel therapeutic option for attenuating CF and improve cardiac function after
MI.
PMID- 29349589
TI - Associations Between Father Temperament, Character, Rearing, Psychopathology and
Child Temperament in Children Aged 3-6 Years.
AB - Temperament refers to the totality of individual characteristics present from
birth that determine a child's unique style of behavior. Maternal personality and
attitudes, one of the factors affecting temperament traits in children, is a
frequently investigated subject. However, paternal variables have remained
insufficiently studied. The purpose of this study is to investigate the
associations between the fathers' temperament, character, attitudes,
psychopathology and temperament of the 3-6 years-old children. The parents of 36
60 months-old children in the preschool settings in Samsun were included in the
study (n:200). Their mothers completed "Maternal Sociodemographic Form" prepared
by the researcher, and the temperament of children "Children Behaviour
Questionnare" were scored by the mothers. Their fathers completed "Paternal
Sociodemographic Form", and to assess father psychopathology "Brief Symptom
Inventory", to determine father temperament and character "Temperament and
Character Inventory" and to determine attitudes "Parenting Attitudes Scale" were
scored by the fathers. In this study, we found several significant associations
between children's temperament and fathers temperament and character, attitudes
styles and psychopathology. The scores of paternal harm avoidance increase and
self directedness decrease were found to be significantly positivily correlated
with negative temperamental charecteristics of the children. The democratic
attitudes of fathers were significantly correlated with positive temperamental
scores of the children. All domains of paternal psychopathology were found to be
in significant association with negative temperamental characteristics of the
children. Our findings showed the complex interplay between determinants of
parenting. Specifically, this study is one of the first to investigate paternal
personality, psychopathology and attitudes, alone and in interaction with
preschool child temperament.
PMID- 29349590
TI - Law as Clinical Evidence: A New ConstitutiveModel of Medical Education and
Decision-Making.
AB - Over several decades, ethics and law have been applied to medical education and
practice in a way that reflects the continuation during the twentieth century of
the strong distinction between facts and values. We explain the development of
applied ethics and applied medical law and report selected results that reflect
this applied model from an empirical project examining doctors' decisions on
withdrawing/withholding treatment from patients who lack decision-making
capacity. The model is critiqued, and an alternative "constitutive" model is
supported on the basis that medicine, medical law, and medical ethics exemplify
the inevitable entanglement of facts and values. The model requires that ethics
and law be taught across the medical education curriculum and integrated with the
basic and clinical sciences and that they be perceived as an integral component
of medical evidence and practice. Law, in particular, would rank as equal in
normative authority to the relevant clinical scientific "facts" of the case, with
graduating doctors having as strong a basic command of each category as the
other. The normalization of legal knowledge as part of the clinician's evidence
base to be utilized in practice may provide adequate consolation for clinicians
who may initially resent further perceived incursions on their traditional
independence and discretion.
PMID- 29349591
TI - Radical resection of a giant retroperitoneal calcifying fibrous tumor combined
with right hepatectomy and reconstruction of the inferior vena cava and bilateral
renal veins.
AB - BACKGROUND: We report a case of a giant retroperitoneal calcifying fibrous tumor
(CFT) treated by radical tumor resection combined with right hepatectomy and
reconstruction of the inferior vena cava (IVC) and bilateral renal veins. Only
three case reports of CFT arising in the retroperitoneum have been reported until
today. CASE PRESENTATION: In a 19-year-old female patient, computed tomography
(CT) images showed a well-demarcated expansile lesion around the IVC accompanied
by focal calcification, whereas the IVC that was circumferentially surrounded by
the lesion was dilated due to the desmoplastic reaction. On magnetic resonance
imaging (MRI), the lesion demonstrated heterogeneous hypointensity on T2-weighted
images. Delayed enhancement was observed on dynamic contrast-enhanced CT and MRI.
18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT images showed
increased FDG uptake [maximum standardized uptake values (SUVmax), early image
7.28; delayed image 7.40]. On operative examination, because the tumor adhered to
the liver parenchyma, the right Glisson capsule, and the origin of bilateral
renal veins, radical tumor resection combined with right hepatectomy and
reconstruction of the IVC and bilateral renal veins was performed. CONCLUSIONS:
Radical tumor resection was successfully and appropriately performed for a young
patient with a giant retroperitoneal CFT with a view to achieving complete venous
reconstruction and safe surgical margins for a potentially malignant tumor.
PMID- 29349592
TI - Overview of Current and Future Adjuvant Therapy for High-Risk Localized Renal
Cell Carcinoma.
AB - OPINION STATEMENT: High-risk localized renal cell carcinoma represents a
therapeutic challenge with high recurrence rates and poor survival with
nephrectomy alone. Multiple agents targeting angiogenic and immunologic pathways
have demonstrated remarkable efficacy in the metastatic setting but have failed
to replicate similar successes in localized disease. Study results with adjuvant
anti-angiogenic therapies may have been compromised by the high incidence of
treatment discontinuations or dosage reductions secondary to intolerable side
effects. Improving patient selection could play a major role in improving
outcomes. Multiple models exist to predict survival but require improved accuracy
in identifying recurrence to justify exposing patients to therapies that could
significantly impair quality of life. Further understanding of pathological and
molecular mechanisms of recurrence is required. Novel tools like gene recurrence
scores are emerging to improve prognostication for patient selection.
Immunotherapeutic approaches using check point inhibition have the potential to
achieve sustained remissions with a significantly improved toxicity profile.
Amplifying the immune response with a combination of neoadjuvant and adjuvant
therapy to exploit the larger antigenic burden prior to nephrectomy has the
biologic potential for making significant improvements in efficacy.
PMID- 29349593
TI - BodiMojo: Efficacy of a Mobile-Based Intervention in Improving Body Image and
Self-Compassion among Adolescents.
AB - Mobile interventions promoting positive body image are lacking. This study
presents a randomized controlled evaluation of BodiMojo, a mobile application
(app) intervention grounded in self-compassion to promote positive body image. A
sample of 274 adolescents, mean (SD) age = 18.36 (1.34) years, 74% female, were
allocated to a control group or used BodiMojo for 6 weeks. Appearance esteem,
body image flexibility, appearance comparison, mood, and self-compassion were
assessed at baseline, 6, and 12 weeks. Significant time by group interactions
emerged for appearance esteem and self-compassion, with appearance esteem and
self-compassion increasing in the intervention relative to the control group.
These findings provide preliminary support for BodiMojo, a cost-effective mobile
app for positive body image.
PMID- 29349594
TI - Pacifists and Revenge-Seekers in Response to Unambiguous Peer Provocation.
AB - In order to better understand why some children retaliate when they feel provoked
and others do not, the present study identified "pacifistically-oriented"
children who made negative interpretations in response to unambiguous
provocations, yet did not endorse revenge goals, and compared them to "revenge
seeking" children who also made negative interpretations but did endorse revenge
goals. Groups were identified based on seventh graders' (N = 367; 54.77% male;
22.89% racial/ethnic minority) responses to hypothetical situations in which a
peer excluded and insulted them. Comparing these groups revealed that Pacifists
endorsed relationship-maintaining goals and emotion regulation goals more highly
than Revenge-Seekers. Revenge-Seekers reported more anger and endorsed beliefs
about negative reciprocity and aggression being legitimate more highly than
Pacifists. Additionally, Revenge-Seekers were more disrespect sensitive than were
Pacifists, based on a measure of vigilance for signs of disrespect and
expectations that others would disrespect them. Together these findings point to
social-cognitive and emotion-related processes that may inhibit revenge-seeking
in unambiguous provocation situations, even when children interpret the peer's
behavior quite negatively.
PMID- 29349595
TI - The Development of a Nano-based Approach to Alleviate Cisplatin-Induced
Ototoxicity.
AB - Cisplatin-induced hearing loss is experienced by a high percentage of patients
with squamous cell carcinoma undergoing cisplatin chemotherapy. A novel nano
construct capable of sequestering extracellular cisplatin was developed to combat
this problem. The nano-construct consisted of superparamagnetic iron oxide
nanoparticles (SPIONs) entrapped within polymeric micelles, which were formed
from a glutathione diethyl ester-conjugated amphiphilic diblock copolymer. The
glutathione-micelles were analyzed at the cellular level and in an organotypic
study for safety evaluation. All utilized methods indicated that the micelles do
not cause cellular toxicity or organ damage. The micelles' ability to reduce
cisplatin-induced cytotoxicity was then probed in an in vitro model. Cisplatin
was pre-treated with the novel nano-construct before being added to growing
cells. When compared to cells that were exposed to untreated cisplatin, cells in
the pre-treated cisplatin group showed a significant increase in cell viability.
This clearly demonstrates that the construct is able to protect the cells from
cisplatin cytotoxicity and makes it highly likely that the novel nano-construct
will be able to play a role in the protection of the inner ear from cisplatin
induced ototoxicity.
PMID- 29349596
TI - Concomitant Use of Antiplatelets and Anticoagulants in Patients with Coronary
Heart Disease and Atrial Fibrillation: What Do Recent Clinical Trials Teach Us?
AB - PURPOSE OF REVIEW: Coronary heart disease (CHD) and atrial fibrillation (AF) are
among the most common cardiovascular diseases. A significant proportion of
patients have both CHD and AF and are at increased risk for thrombotic
complications. Current therapy for CHD and AF includes antiplatelet and
anticoagulant medications, respectively. Patients with concurrent CHD and AF may
be prescribed dual antiplatelet therapy (DAPT) in addition to anticoagulation,
which increases their bleeding risk. Controversy remains on how to balance risks
and benefits in patients with CHD and AF in which multiple antithrombotic
therapies may be indicated. RECENT FINDINGS: We review clinical trials and
current guidelines for antiplatelet and anticoagulant therapy in CHD and AF.
Aspirin and P2Y12 inhibitors are the mainstay of antiplatelet therapy. Vitamin K
antagonists (VKAs) are the most commonly used anticoagulant, although the use of
non-VKA oral anticoagulants (NOACs) in patients with AF is increasing. Recent
studies provide guidance on how to address antithrombotic therapies in patients
with concomitant CHD and AF. To date, we have evidence that in patients with AF
who undergo percutaneous coronary intervention (PCI), clopidogrel with VKA may be
used safely without aspirin. Also, low-dose rivaroxaban in combination with
either clopidogrel only or DAPT is as effective as the traditional regimen of
triple therapy with VKA and DAPT with lower bleeding risk. Dabigatran with a
P2Y12 inhibitor was also found to be safe with less bleeding compared to triple
therapy with VKA and DAPT. Use of a single antiplatelet agent with
anticoagulation has become a viable choice in patients with CHD and AF, but more
clinical trial data is needed to confirm therapy and duration regimens.
PMID- 29349597
TI - Drug repurposing screening identifies bortezomib and panobinostat as drugs
targeting cancer associated fibroblasts (CAFs) by synergistic induction of
apoptosis.
AB - Cancer associated fibroblasts (CAFs) are the most abundant components of cancer
microenvironment. They play important roles in cancer initiation, progression,
and metastasis. In addition, CAFs can confer drug-resistance to cancer cells.
Considering their pro-tumorigenic roles, it is recommended to remove CAFs to
prevent cancer recurrence after chemotherapy. Despite their clinical
significance, few anti-CAF drugs have been developed. The objective of this study
was to find a drug that could suppress the viability of patient-derived CAFs
through repurposed screening of 51 drugs that were in clinical trials or received
FDA approval. As a result, bortezomib (BTZ), carfilzomib (CFZ), and panobinostat
(PST) were identified as anti-CAF drug candidates. It was confirmed that BTZ and
PST could decrease the viability of various patients derived CAFs through
inducing of caspase-3 mediated apoptosis. Interestingly, combination therapy with
BTZ and PST showed better efficacy of inhibiting CAFs than single treatment. The
synergistic effect between BTZ and PST on viability of CAFs was observed both in
vitro CAF culture and in vivo mouse model. Furthermore, combination therapy with
BTZ/PST and conventional anticancer compound docetaxel strongly inhibited tumor
growth in xenografts of mouse breast cancer cells with mouse CAFs. In conclusion,
our present study revealed that BTZ and PST could significantly reduce the
viability of CAFs. Therefore, a combination therapy with BTZ/PST and anticancer
drugs might be considered as a new rational for the development of anticancer
therapy.
PMID- 29349599
TI - Evolution of Eukaryal and Archaeal Pseudouridine Synthase Pus10.
AB - In archaea, pseudouridine (Psi) synthase Pus10 modifies uridine (U) to Psi at
positions 54 and 55 of tRNA. In contrast, Pus10 is not found in bacteria, where
modifications at those two positions are carried out by TrmA (U54 to m5U54) and
TruB (U55 to Psi55). Many eukaryotes have an apparent redundancy; their genomes
contain orthologs of archaeal Pus10 and bacterial TrmA and TruB. Although
eukaryal Pus10 genes share a conserved catalytic domain with archaeal Pus10
genes, their biological roles are not clear for the two reasons. First,
experimental evidence suggests that human Pus10 participates in apoptosis induced
by the tumor necrosis factor-related apoptosis-inducing ligand. Whether the
function of human Pus10 is in place or in addition to of Psi synthesis in tRNA is
unknown. Second, Pus10 is found in earlier evolutionary branches of fungi (such
as chytrid Batrachochytrium) but is absent in all dikaryon fungi surveyed
(Ascomycetes and Basidiomycetes). We did a comprehensive analysis of sequenced
genomes and found that orthologs of Pus10, TrmA, and TruB were present in all the
animals, plants, and protozoa surveyed. This indicates that the common eukaryotic
ancestor possesses all the three genes. Next, we examined 116 archaeal and
eukaryotic Pus10 protein sequences to find that Pus10 existed as a single copy
gene in all the surveyed genomes despite ancestral whole genome duplications had
occurred. This indicates a possible deleterious gene dosage effect. Our results
suggest that functional redundancy result in gene loss or neofunctionalization in
different evolutionary lineages.
PMID- 29349600
TI - Beneficial Mutations from Evolution Experiments Increase Rates of Growth and
Fermentation.
AB - A major goal of evolutionary biology is to understand how beneficial mutations
translate into increased fitness. Here, we study beneficial mutations that arise
in experimental populations of yeast evolved in glucose-rich media. We find that
fitness increases are caused by enhanced maximum growth rate (R) that come at the
cost of reduced yield (K). We show that for some of these mutants, high R
coincides with higher rates of ethanol secretion, suggesting that higher growth
rates are due to an increased preference to utilize glucose through the
fermentation pathway, instead of respiration. We examine the performance of
mutants across gradients of glucose and nitrogen concentrations and show that the
preference for fermentation over respiration is influenced by the availability of
glucose and nitrogen. Overall, our data show that selection for high growth rates
can lead to an enhanced Crabtree phenotype by the way of beneficial mutations
that permit aerobic fermentation at a greater range of glucose concentrations.
PMID- 29349598
TI - Phase Ib study evaluating safety and clinical activity of the anti-HER3 antibody
lumretuzumab combined with the anti-HER2 antibody pertuzumab and paclitaxel in
HER3-positive, HER2-low metastatic breast cancer.
AB - : Purpose To investigate the safety and clinical activity of comprehensive human
epidermal growth factor receptor (HER) family receptor inhibition using
lumretuzumab (anti-HER3) and pertuzumab (anti-HER2) in combination with
paclitaxel in patients with metastatic breast cancer (MBC). Methods This phase Ib
study enrolled 35 MBC patients (first line or higher) with HER3-positive and HER2
low (immunohistochemistry 1+ to 2+ and in-situ hybridization negative) tumors.
Patients received lumretuzumab (1000 mg in Cohort 1; 500 mg in Cohorts 2 and 3)
plus pertuzumab (840 mg loading dose [LD] followed by 420 mg in Cohorts 1 and 2;
420 mg without LD in Cohort 3) every 3 weeks, plus paclitaxel (80 mg/m2 weekly in
all cohorts). Patients in Cohort 3 received prophylactic loperamide treatment.
Results Diarrhea grade 3 was a dose-limiting toxicity of Cohort 1 defining the
maximum tolerated dose of lumretuzumab when given in combination with pertuzumab
and paclitaxel at 500 mg every three weeks. Grade 3 diarrhea decreased from 50%
(Cohort 2) to 30.8% (Cohort 3) with prophylactic loperamide administration and
omission of the pertuzumab LD, nonetheless, all patients still experienced
diarrhea. In first-line MBC patients, the objective response rate in Cohorts 2
and 3 was 55% and 38.5%, respectively. No relationship between HER2 and HER3
expression or somatic mutations and clinical response was observed. Conclusions
Combination treatment with lumretuzumab, pertuzumab and paclitaxel was associated
with a high incidence of diarrhea. Despite the efforts to alter dosing, the
therapeutic window remained too narrow to warrant further clinical development.
TRIAL REGISTRATION: on ClinicalTrials.gov with the identifier NCT01918254 first
registered on 3rd July 2013.
PMID- 29349601
TI - Prospective feasibility analysis of a novel off-line approach for MR-guided
radiotherapy.
AB - BACKGROUND: The present work aimed to analyze the feasibility of a shuttle-based
MRI-guided radiation therapy (MRgRT) in the treatment of pelvic malignancies.
PATIENTS AND METHODS: 20 patients with pelvic malignancies were included in this
prospective feasibility analysis. Patients underwent daily MRI in treatment
position prior to radiotherapy at the German Cancer Research Center. Positional
inaccuracies, time and patient compliance were assessed for the application of
off-line MRgRT. RESULTS: In 78% of applied radiation fractions, MR imaging for
position verification could be performed without problems. Additionally,
treatment-related side effects and reduced patient compliance were only
responsible for omission of MRI in 9% of radiation fractions. The study workflow
took a median time of 61 min (range 47-99 min); duration for radiotherapy alone
was 13 min (range 7-26 min). Patient positioning, MR imaging and CT imaging
including patient repositioning and the shuttle transfer required median times of
10 min (range 7-14 min), 26 min (range 15-60 min), 5 min (range 3-8 min) and 8
min (range 2-36 min), respectively. To assess feasibility of shuttle-based MRgRT,
the reference point coordinates for the x, y and z axis were determined for the
MR images and CT obtained prior to the first treatment fraction and correlated
with the coordinates of the planning CT. In our dataset, the median positional
difference between MR imaging and CT-based imaging based on fiducial matching
between MR and CT imaging was equal to or less than 2 mm in all spatial
directions. The limited space in the MR scanner influenced patient selection, as
the bore of the scanner had to accommodate the immobilization device and the
constructed stereotactic frame. Therefore, obese, extremely muscular or very tall
patients could not be included in this trial in addition to patients for whom
exposure to MRI was generally judged inappropriate. CONCLUSION: This trial
demonstrated for the first time the feasibility and patient compliance of a
shuttle-based off-line approach to MRgRT of pelvic malignancies.
PMID- 29349602
TI - Does the interval from tumour surgery to radiotherapy influence survival in
paediatric high grade glioma?
AB - PURPOSE: Paediatric high grade glioma (pHGG) are rare. Following maximum safe
resection, children >3 years with HGG receive radiotherapy as standard of care.
Whether the interval from tumour surgery to radiotherapy (ISRT) influences
survival is disputed in adults with glioblastoma, data for children are lacking.
This retrospective single-centre analysis investigates a possible impact of ISRT
on survival in paediatric patients with HGG. METHODS: Survival was analysed in
patients aged 3-19 years with non-pontine HGG. RESULTS: Thirty-eight patients
were included (female:male 19:19) with a median age of 11.0 years (3.4-17.7).
Seventeen patients had grade 3 and 21 grade 4 glioma. Gross total resection was
achieved in 26.3%, partial resection in 36.8% and 36.8% underwent biopsy only.
All patients received concomitant and adjuvant chemotherapy. Fifty percent (n =
19) started irradiation <=17 days (median interval 12 days [range 5-17]), 50%
thereafter (median 28 days [range 19-78]). More patients with grade 4 tumours
were irradiated shortly after surgery. ISRT (as a continuous variable and
dichotomised into two groups by the median ISRT of 18 days) did not significantly
influence overall survival (OS) or progression-free survival (PFS). Higher extent
of resection (EOR), lower tumour grade as well as chemotherapy with temozolomide
had a significant positive impact on OS and PFS in univariate analysis and
(except for the effect of temozolomide on PFS) also in multivariable analysis.
CONCLUSIONS: ISRT did not influence survival in pHGG. In view of upcoming
targeted treatment options in pHGG the present data suggest that it is safe to
perform molecular analyses within a 4-week timeframe before radiotherapy.
PMID- 29349603
TI - Neoadjuvant chemoradiation for esophageal cancer : Surgery improves locoregional
control while response based on FDG-PET/CT predicts survival.
AB - INTRODUCTION: To retrospectively analyze the outcome of patients with esophageal
cancer treated with neoadjuvant chemoradiation. METHODS: A total of 41 patients
received neoadjuvant intent chemoradiation for esophageal cancer. Most patients
had a locally advanced disease (T3/4: 82%, N+: 83%, M0: 100%) and squamous cell
carcinoma (83%). All patients received concurrent chemotherapy with cisplatin/5
fluorouracil or mitomycin/5-fluorouracil. Median radiation dose was 50.4 Gy in
the 25 patients who proceeded to surgery and 57.4 Gy in 16 patients who did not
undergo surgery. FDG-PET/CT was used for treatment planning in 24 patients. A
second FDG-PET/CT was available for response evaluation in 18 patients. RESULTS:
Median follow-up was 16 months in all patients and 30 months in survivors.
Radiotherapy was completed without interruptions >3 days in 90% of patients, and
chemotherapy was carried out to >80% in 85% of patients. The 2-year locoregional
control rate was 60%, distant control rate 54% and overall survival rate 50%.
Hematological toxicity grade 3/4 was observed in 34%/10% of patients and non
hematological toxicity grade 3/4 in 46%/2% of patients. Perioperative 30-day
mortality was 4%. Subgroup analyses revealed that surgery significantly improved
locoregional control (74% vs. 39%, p = 0.034), but not the 2-year survival rate
(54% vs. 43%, p = 0.246). In contrast, response based on FDG-PET/CT prior and
after chemoradiation significantly predicted improved overall survival (2-year
overall survival 61% vs. 40%, p = 0.048). CONCLUSION: Outcomes of our cohort were
comparable to other series using similar treatments. Surgery significantly
improved locoregional control but not survival. Response based on FDG-PET/CT
predicted survival and might be used for treatment stratification.
PMID- 29349604
TI - Quality of training in radiation oncology in Germany: where do we stand? :
Results from a 2016/2017 survey performed by the working group "young DEGRO" of
the German society of radiation oncology (DEGRO).
AB - PURPOSE: To evaluate the current situation of young radiation oncologists in
Germany with regard to the contents and quality of training and level of
knowledge, as well as their working conditions and professional satisfaction.
METHODS: From June 2016 to February 2017, a survey was conducted by the young
DEGRO (yDEGRO) using an online platform. The questionnaire consisted of 28 items
examining a broad range of aspects influencing residency. There were 96 completed
questionnaires RESULTS: 83% of participants stated to be very or mostly pleased
with their residency training. Moderate working hours and a good colleagueship
contribute to a comfortable working environment. Level of knowledge regarding the
most common tumor sites (i.e. palliative indications, lung, head and neck, brain,
breast, prostate) was pleasing. Radiochemotherapy embodies a cornerstone in
training. Modern techniques such as intensity-modulated radiotherapy (IMRT) and
stereotactic procedures are now in widespread use. Education for rare indications
and center-based procedures offers room for improvement. CONCLUSION: Radiation
oncology remains an attractive and versatile specialty with favorable working
conditions. Continuing surveys in future years will be a valuable measuring tool
to set further priorities in order to preserve and improve quality of training.
PMID- 29349606
TI - Well-Differentiated Liposarcoma (Atypical Lipomatous Tumor) Presenting as an
Esophageal Polyp.
PMID- 29349605
TI - Improved effectiveness of stereotactic radiosurgery in large brain metastases by
individualized isotoxic dose prescription: an in silico study.
AB - INTRODUCTION: In large brain metastases (BM) with a diameter of more than 2 cm
there is an increased risk of radionecrosis (RN) with standard stereotactic
radiosurgery (SRS) dose prescription, while the normal tissue constraint is
exceeded. The tumor control probability (TCP) with a single dose of 15 Gy is only
42%. This in silico study tests the hypothesis that isotoxic dose prescription
(IDP) can increase the therapeutic ratio (TCP/Risk of RN) of SRS in large BM.
MATERIALS AND METHODS: A treatment-planning study with 8 perfectly spherical and
46 clinically realistic gross tumor volumes (GTV) was conducted. The effects of
GTV size (0.5-4 cm diameter), set-up margins (0, 1, and 2 mm), and beam
arrangements (coplanar vs non-coplanar) on the predicted TCP using IDP were
assessed. For single-, three-, and five-fraction IDP dose-volume constraints of
V12Gy = 10 cm3, V19.2 Gy = 10 cm3, and a V20Gy = 20 cm3, respectively, were used
to maintain a low risk of radionecrosis. RESULTS: In BM of 4 cm in diameter, the
maximum achievable single-fraction IDP dose was 14 Gy compared to 15 Gy for
standard SRS dose prescription, with respective TCPs of 32 and 42%. Fractionated
SRS with IDP was needed to improve the TCP. For three- and five-fraction IDP, a
maximum predicted TCP of 55 and 68% was achieved respectively (non-coplanar beams
and a 1 mm GTV-PTV margin). CONCLUSIONS: Using three-fraction or five-fraction
IDP the predicted TCP can be increased safely to 55 and 68%, respectively, in
large BM with a diameter of 4 cm with a low risk of RN. Using IDP, the
therapeutic ratio of SRS in large BM can be increased compared to current SRS
dose prescription.
PMID- 29349607
TI - Molecular characterization of Fagaceae species using inter-primer binding site
(iPBS) markers.
AB - Retrotransposons (RTNs) contribute for genome evolution, influencing its size and
structure. We investigated the utility of the RTN-based markers inter-primer
binding site (iPBS) for the molecular characterization of 25 Fagaceae species
from genera Castanea, Fagus and Quercus. The assessment of genetic diversity,
relationships and structure, as well as taxonomic classification of Fagaceae
based on molecular data is important for definition of conservation, forestry
management strategies and discrimination among natural hybrids and their parents
since natural hybridization may increase with the climate changes. Here, iPBS
primers designed by other authors were tested alone and combined. Some of them
were discriminative, revealed polymorphism within and among taxa allowing the
production of a total of 150 iPBS markers. In addition, several monomorphic iPBS
markers were also amplified in each taxon. The UPGMA dendrogram based on the
pooled iPBS data revealed 27% of genetic similarity among species. The
individuals were clustered per genus and most of the oaks per infrageneric group
corroborating the adopted taxonomy. Globally, the iPBS markers demonstrated
suitability for DNA fingerprinting, determination of phylogenies and taxonomic
discrimination in Fagaceae, and could constitute a useful and alternative tool
for germplasm characterization, and for definition of conservation strategies and
forestry management. Moreover, these markers would be useful for fingerprinting
natural hybrids that share morphological similarities with their parents. Since
iPBS markers could also enable insights about RTNs evolution, an eventual
correlation among iPBS polymorphism, variability of RTN insertions and/or genome
size in Fagaceae is discussed.
PMID- 29349609
TI - Caspase-1-Mediated Pyroptosis of the Predominance for Driving CD4[Formula: see
text] T Cells Death: A Nonlocal Spatial Mathematical Model.
AB - Caspase-1-mediated pyroptosis is the predominance for driving CD4[Formula: see
text] T cells death. Dying infected CD4[Formula: see text] T cells can release
inflammatory signals which attract more uninfected CD4[Formula: see text] T cells
to die. This paper is devoted to developing a diffusive mathematical model which
can make useful contributions to understanding caspase-1-mediated pyroptosis by
inflammatory cytokines IL-1[Formula: see text] released from infected cells in
the within-host environment. The well-posedness of solutions, basic reproduction
number, threshold dynamics are investigated for spatially heterogeneous
infection. Travelling wave solutions for spatially homogeneous infection are
studied. Numerical computations reveal that the spatially heterogeneous infection
can make [Formula: see text], that is, it can induce the persistence of virus
compared to the spatially homogeneous infection. We also find that the random
movements of virus have no effect on basic reproduction number for the spatially
homogeneous model, while it may result in less infection risk for the spatially
heterogeneous model, under some suitable parameters. Further, the death of
infected CD4[Formula: see text] cells which are caused by pyroptosis can make
[Formula: see text], that is, it can induce the extinction of virus, regardless
of whether or not the parameters are spatially dependent.
PMID- 29349608
TI - Comparative transcriptomics uncovers differences in photoautotrophic versus
photoheterotrophic modes of nutrition in relation to secondary metabolites
biosynthesis in Swertia chirayita.
AB - Swertia chirayita is a high-value medicinal herb exhibiting antidiabetic,
hepatoprotective, anticancer, antiediematogenic and antipyretic properties.
Scarcity of its plant material has necessitated in vitro production of
therapeutic metabolites; however, their yields were low compared to field grown
plants. Possible reasons for this could be differences in physiological and
biochemical processes between plants grown in photoautotrophic versus
photoheterotrophic modes of nutrition. Comparative transcriptomes of S. chirayita
were generated to decipher the crucial molecular components associated with the
secondary metabolites biosynthesis. Illumina HiSeq sequencing yielded 57,460 and
43,702 transcripts for green house grown (SCFG) and tissue cultured (SCTC)
plants, respectively. Biological role analysis (GO and COG assignments) revealed
major differences in SCFG and SCTC transcriptomes. KEGG orthology mapped 351 and
341 transcripts onto secondary metabolites biosynthesis pathways for SCFG and
SCTC transcriptomes, respectively. Nineteen out of 30 genes from primary
metabolism showed higher in silico expression (FPKM) in SCFG versus SCTC,
possibly indicating their involvement in regulating the central carbon pool. In
silico data were validated by RT-qPCR using a set of 16 genes, wherein 10 genes
showed similar expression pattern across both the methods. Comparative
transcriptomes identified differentially expressed transcription factors and ABC
type transporters putatively associated with secondary metabolism in S.
chirayita. Additionally, functional classification was performed using NCBI
Biosystems database. This study identified the molecular components implicated in
differential modes of nutrition (photoautotrophic vs. photoheterotrophic) in
relation to secondary metabolites production in S. chirayita.
PMID- 29349611
TI - Abstracts of the 6th international multiple system atrophy congress.
PMID- 29349610
TI - Ligand Binding Dynamics for Pre-dimerised G Protein-Coupled Receptor Homodimers:
Linear Models and Analytical Solutions.
AB - Evidence suggests that many G protein-coupled receptors (GPCRs) are bound
together forming dimers. The implications of dimerisation for cellular signalling
outcomes, and ultimately drug discovery and therapeutics, remain unclear.
Consideration of ligand binding and signalling via receptor dimers is therefore
required as an addition to classical receptor theory, which is largely built on
assumptions of monomeric receptors. A key factor in developing theoretical models
of dimer signalling is cooperativity across the dimer, whereby binding of a
ligand to one protomer affects the binding of a ligand to the other protomer.
Here, we present and analyse linear models for one-ligand and two-ligand binding
dynamics at homodimerised receptors, as an essential building block in the
development of dimerised receptor theory. For systems at equilibrium, we compute
analytical solutions for total bound labelled ligand and derive conditions on the
cooperativity factors under which multiphasic log dose-response curves are
expected. This could help explain data extracted from pharmacological experiments
that do not fit to the standard Hill curves that are often used in this type of
analysis. For the time-dependent problems, we also obtain analytical solutions.
For the single-ligand case, the construction of the analytical solution is
straightforward; it is bi-exponential in time, sharing a similar structure to the
well-known monomeric competition dynamics of Motulsky-Mahan. We suggest that this
model is therefore practically usable by the pharmacologist towards developing
insights into the potential dynamics and consequences of dimerised receptors.
PMID- 29349612
TI - Dexamethasone-induced leukocytosis is associated with poor survival in newly
diagnosed glioblastoma.
AB - Despite its well-characterized side effects, dexamethasone is widely used in the
pre-, peri- and postoperative neurosurgical setting due to its effective relief
of tumor-induced symptoms through the reduction of tumor-associated edema.
However, some patients show laboratory-defined dexamethasone induced elevation of
white blood cell count, and its impact on glioblastoma progression is unknown. We
retrospectively analyzed 113 patients with newly diagnosed glioblastoma to
describe the incidence, risk factors and clinical features of dexamethasone
induced leukocytosis in primary glioblastoma patients. We further conducted an
immunohistochemical analysis of the granulocyte and lymphocyte tumor-infiltration
in the available corresponding histological sections. Patient age was identified
to be a risk factor for the development of dexamethasone-induced leukocytosis (p
< 0.05). The presence of dexamethasone-induced leukocytosis decreased overall
survival (HR 2.25 95% CI [1.15-4.38]; p < 0.001) and progression-free survival
(HR 2.23 95% CI [1.09-4.59]; p < 0.01). Furthermore, patients with dexamethasone
induced leukocytosis had significantly reduced CD15 + granulocytic- (p < 0.05)
and CD3 + lymphocytic tumour infiltration (p < 0.05). We identified a subgroup of
glioblastoma patients that are at particularly high risk for poor outcome upon
dexamethasone treatment. Therefore, restrictive dosage or other edema reducing
substances should be considered in patients with dexamethasone-induced
leukocytosis.
PMID- 29349613
TI - Tumor treating fields: a new approach to glioblastoma therapy.
AB - Glioblastoma is an aggressive brain malignancy with poor outcomes. Current
standard of care involves surgery, radiotherapy and chemotherapy. Even with
optimal treatment, 5-year survival rates are low. Many patients are unable to
tolerate the considerable side effects that therapy involves and suffer from low
quality of life. Anti-mitotic tumor treating fields have shown potential in
treating glioblastoma with data suggesting that they prolong disease-free
survival and overall survival. Novocure has marketed a device that generates
these fields via externally placed electrodes. Incorporation of electric field
therapy into GBM treatment has been somewhat slow, due to concerns about cost,
practicality of its usage from a patient perspective, and hesitation of the
medical and scientific community to embrace its unconventional mechanism.
However, clinical trials have demonstrated this therapy has relatively minor side
effects and high patient compliance. In this review, we explore the current state
of this technology and discuss the benefits and limitations of tumor treating
fields.
PMID- 29349614
TI - Treatment and outcomes of 28 patients with spinal metastasis from gynecological
cancer.
AB - The aim of this study was to provide some useful information concerning clinical
characteristics, surgical treatment, potential contributing factor and prognostic
factors for patients with gynecological cancer (GC) spinal metastasis. We
reviewed 28 patients with GC spinal metastasis in our spine tumor center between
July 2008 and July 2015. Surgeries were performed on 22 of them. Univariate and
multivariate analyses were conducted to identify potential prognostic factors
affecting spinal metastasis-free survival (SMFS) and overall survival. The
operative patients responded favorably according to decrease of VAS score and
increase of Frankel grade after surgery. The 1- and 2-year survival rates in all
patients were 60.7 and 41.0%, respectively. Univariate analysis suggested that
age at diagnosis with GC was the potential contributing factor for spinal
metastasis, while Frankel grade, ECOG-PS, visceral metastasis and chemotherapy
were the potential prognostic factors affecting survival. Multivariate analysis
indicated that the independent prognostic factors came from visceral metastasis
and chemotherapy. Surgery played an important role in improving patients' quality
of life. Patients over 50 years old had a shorter SMFS after diagnosed with GC.
Visceral metastasis was an adverse prognostic factor for patients with GC spinal
metastasis, while chemotherapy was a favorable one.
PMID- 29349615
TI - Long-term follow-up (at 5 years) of midline incisional hernia repairs using a
primary closure and prosthetic onlay technique: recurrence and quality of life.
AB - INTRODUCTION AND OBJECTIVES: The recurrence rate of incisional hernia (IH) repair
is usually underestimated due to a lack of long-term follow-up. The objective of
this study was to evaluate recurrence rate for patients operated on midline IH
surgery, using a primary closure and prosthetic onlay technique, 5 years after
the procedure. MATERIALS AND METHODS: From January 2009 to January 2011, all 92
patients operated on elective midline IH repair by primary closure and prosthetic
onlay technique in a General Surgery Department were retrospectively included in
the study. Exclusion criteria were absence of follow-up or death. Recurrence rate
and quality of life were assessed. Demographic, surgical data and quality of life
in patients with and without 5-year recurrence were compared. RESULTS: Mean
follow-up was 64 months. Ultimately, 76 patients were included in the study,
representing 82% of the selected patients during the study period (76/92), of
whom 24 presented a recurrence (32%). Half (12) were diagnosed for recurrence
more than 3 years after the surgery. Patients who developed a recurrence had more
percentage of obesity (64 vs. 29%, p = 0.016), which denoted an odds ratio (OR)
for recurrence of 4.4 (1.2-15.7; p = 0.01) and they punctuated lower in quality
of life (6.0 +/- 2.9 vs. 7.6 +/- 2.6, p = 0.006). CONCLUSIONS: Recurrence rate on
midline IH repair is still a concern (32% at 5 years). It is advisable to look
for other strategies and more efficient surgical techniques for IH surgery,
especially in obese patients.
PMID- 29349616
TI - Outcomes of utilizing absorbable mesh as an adjunct to posterior sheath closure
during complex posterior component separation.
AB - BACKGROUND: A minority of patients undergoing posterior component separation
(PCS) have abdominal wall defects that preclude complete reconstruction of the
visceral sac with native tissue. The use of absorbable mesh bridges (AMB) to span
such defects has not been established. We hypothesized that AMB use during
posterior sheath closure of PCS is safe and provides favorable outcomes. METHODS:
We performed a retrospective review of consecutive patients undergoing PCS with
AMB at two hernia centers. Main outcome measures included demographics,
comorbidities, and post-operative complications. RESULTS: 36 patients were
identified. Post-operative wound complications included five surgical site
infections. At a median of 27 months, there were five recurrent hernias (13.9%),
2 of which were parastomal, but no episodes of intestinal obstruction/fistula.
CONCLUSIONS: Utilization of AMB for large posterior layer deficits results in
acceptable rates of perioperative wound morbidity, effective PCS repairs, and
does not increase intestinal morbidity or fistula formation.
PMID- 29349617
TI - Use of venovenous ECMO for neonatal and pediatric ECMO: a decade of experience at
a tertiary children's hospital.
AB - BACKGROUND: Advances in extracorporeal membrane oxygenation (ECMO) have led to
increased use of venovenous (VV) ECMO in the pediatric population. We present the
evolution and experience of pediatric VV ECMO at a tertiary care institution.
METHODS: A retrospective cohort study from 01/2005 to 07/2016 was performed,
comparing by cannulation mode. Survival to discharge, complications, and
decannulation analyses were performed. RESULTS: In total, 160 patients (105 NICU,
55 PICU) required 13 +/- 11 days of ECMO. VV cannulation was used primarily in 83
patients with 64% survival, while venoarterial (VA) ECMO was used in 77 patients
with 54% survival. Overall, 74% of patients (n = 118) were successfully
decannulated; 57% survived to discharge. VA ECMO had a higher rate of intra
cranial hemorrhage than VV (22 vs 9%, p = 0.003). Sixteen VA patients (21%) had
radiographic evidence of a cerebral ischemic insult. No cardiac complications
occurred with the use of dual-lumen VV cannulas. There were no differences in
complications (p = 0.40) or re-operations (p = 0.85) between the VV and VA
groups. CONCLUSION: Dual-lumen VV ECMO can be safely performed with appropriate
image guidance, is associated with a lower rate of intra-cranial hemorrhage, and
may be the preferred first-line mode of ECMO support in appropriately selected
NICU and PICU patients. LEVEL OF EVIDENCE: II.
PMID- 29349618
TI - Respiratory Training Late After Fontan Intervention: Impact on Cardiorespiratory
Performance.
AB - Fontan palliation allows patients with "single ventricle" circulation to reach
adulthood with an acceptable quality of life, although exercise tolerance is
significantly reduced. To assess whether controlled respiratory training (CRT)
increases cardiorespiratory performance. 16 Adolescent Fontan patients (age 17. 5
+/- 3.8 years) were enrolled. Patients were divided into CRT group (n = 10) and
control group (C group, n = 6). Maximal cardiopulmonary test (CPT) was repeated
at the end of CRT in the CRT group and after an average time of 3 months in the C
group. In the CRT group a CPT endurance was also performed before and after CRT.
In the CRT group there was a significant improvement in cardiovascular and
respiratory response to exercise after CRT. Actually, after accounting for
baseline values, the CRT group had decreased breathing respiratory reserve (- 15,
95% CI -22.3 to - 8.0, p = 0.001) and increased RR peak (+ 4.8, 95% CI 0.7-8.9, p
= 0.03), VE peak (+ 13.7, 95% CI 5.6-21.7, p = 0.004), VO2 of predicted (+ 8.5,
95% CI 0.1-17.0, p = 0.05), VO2 peak (+ 4.3, 95% CI 0.3 to 8.2, p = 0.04), and
VO2 workslope (+ 1.7, 95% CI 0.3-3.1, p = 0.02) as compared to the control group.
Moreover, exercise endurance time increased from 8.45 to 17.7 min (p = 0.01). CRT
improves cardiorespiratory performance in post-Fontan patients leading to a
better aerobic capacity.
PMID- 29349619
TI - 1H, 15N, and 13C chemical shift assignments of the micelle immersed FAT C
terminal (FATC) domains of the human protein kinases ataxia-telangiectasia
mutated (ATM) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) fused
to the B1 domain of streptococcal protein G (GB1).
AB - FAT C-terminal (FATC) is a circa 33 residue-long domain. It controls the kinase
functionality in phosphatidylinositol-3 kinase-related kinases (PIKKs). Recent
NMR- and CD-monitored interaction studies indicated that the FATC domains of all
PIKKs can interact with membrane mimetics albeit with different preferences for
membrane properties such as surface charge and curvature. Thus they may generally
act as membrane anchoring unit. Here, we present the 1H, 15N, and 13C chemical
shift assignments of the DPC micelle immersed FATC domains of the human PIKKs
ataxia-telangiectasia mutated (ATM, residues 3024-3056) and DNA protein kinase
catalytic subunit (DNA-PKcs, residues 4096-4128), both fused to the 56 residue
long B1 domain of Streptococcal protein G (GB1). Each fusion protein is 100 amino
acids long and contains in the linking region between the GB1 tag and the FATC
region a thrombin (LVPRGS) and an enterokinase (DDDDK) protease site. The
assignments pave the route for the detailed structural characterization of the
membrane mimetic bound states, which will help to better understand the role of
the proper cellular localization at membranes for the function and regulation of
PIKKs. The chemical shift assignment of the GB1 tag is useful for NMR
spectroscopists developing new experiments or using GB1 otherwise for case
studies in the field of in-cell NMR spectroscopy or protein folding. Moreover it
is often used as purification tag. Earlier we showed already that GB1 does not
interact with membrane mimetics and thus does not disturb the NMR monitoring of
membrane mimetic interactions of attached proteins.
PMID- 29349620
TI - Fatal Talaromyces marneffei Infection in a Patient with Autoimmune Hepatitis.
AB - Talaromyces marneffei, previously known as Penicillium marneffei, is the most
important pathogenic thermally dimorphic fungus causing systemic mycosis in
Southeast Asia. Traditionally, T. marneffei infection in human was mainly
associated with acquired immunodeficiency syndrome caused by HIV infection. In
recent years, there has been an increasing number of T. marneffei infections
reported in non-HIV-infected patients with other immunocompromised conditions,
including autoantibodies against interferon-gamma, systemic lupus erythematosis,
solid organ transplantation, Job's syndrome, hematological malignancies, and use
of novel targeted therapies. In this article, we describe the first case of fatal
T. marneffei infection in a patient with underlying autoimmune hepatitis,
presented as fever without localizing features. The diagnosis of talaromycosis
was confirmed with the identification of the fungi isolated from the blood
culture specimen by conventional methods and using matrix-assisted laser
desorption-ionization time-of-flight mass spectrometer. This case shows the
importance of a high index of suspicion, particularly for such a highly fatal but
potentially treatable fungal infection.
PMID- 29349621
TI - Adsorption and leaching of novel fungicide pyraoxystrobin on soils by 14C tracing
method.
AB - Pyraoxystrobin, (E)-2-(2-((3-(4-chlorophenyl)-1-methyl-1H-pyrazole-5
yloxy)methyl)phenyl)-3-methoxyacrylate, is a newly developed strobilurin
fungicide with high antifungal efficiency. It has high potential to enter soil
environments that might subsequently impact surface and groundwater. Therefore,
14C-labeled pyraoxystrobin was used as a tracer to study the
adsorption/desorption and migration behavior of this compound under laboratory
conditions in three typical agricultural soils. The adsorption isotherms
conformed with the Freundlich equation. Single factor analysis showed that
organic matter content was the most important factor influencing the adsorption.
The highest adsorption level was measured in soil with low pH and high organic
carbon content. Once adsorbed, only 2.54 to 6.41% of the adsorbed compound could
be desorbed. In addition, the mobility results from thin-layer chromatography and
column leaching studies showed that it might be safe to use pyraoxystrobin as a
fungicide without causing groundwater pollution from both runoff and leaching,
which might be attributed to its strong hydrophobicity. High organic matter
content enhanced pyraoxystrobin adsorption and desorption because of the rule of
similarity (lipid solubility). In the column leaching study, 95.02% (minimum
value) of the applied 14C remained within the upper 4.0-cm layer after 60 days.
PMID- 29349622
TI - Transfusion practice patterns in patients with anemia receiving myelosuppressive
chemotherapy for nonmyeloid cancer: results from a prospective observational
study.
AB - PURPOSE: The decision to prescribe packed red blood cell (PRBC) transfusions in
patients with chemotherapy-induced anemia (CIA) includes assessment of clinical
features such as the patient's cancer type and treatment regimen, severity of
anemia symptoms, and presence of comorbidities. We examined contemporary
transfusion practices in patients with nonmyeloid cancer and CIA. METHODS: Key
inclusion criteria were age >= 18 years with nonmyeloid cancer, receiving
first/second-line myelosuppressive chemotherapy, baseline hemoglobin (Hb) <= 10.0
g/dL, and planned to receive >= 1 PRBC transfusions. Exclusion criteria were
receipt of erythropoiesis-stimulating agents within 8 weeks of screening and/or
chronic renal insufficiency. Data were collected from patients' medical records,
laboratory values, and physician/provider questionnaires. Proportion of patients
for each clinical consideration leading to a decision to prescribe a PRBC
transfusion and 95% exact binomial confidence intervals were determined. RESULTS:
The study enrolled 154 patients at 18 sites in USA; 147 (95.5%) received a PRBC
transfusion. Fatigue was the most common symptom affecting the decision to
prescribe a PRBC transfusion (101 [69.2%] patients). Of the three reasons
selected as primary considerations for prescribing a PRBC transfusion, anemia
symptoms (106 [72.1%] patients) was the most frequently reported, followed by Hb
value (37 [25.2%] patients) and medical history (4 [2.7%] patients). CONCLUSIONS:
In this study, the primary consideration for prescribing a PRBC transfusion was
anemia symptoms in 72.1% of patients, with only 25.2% of patients prescribed a
transfusion based exclusively on Hb value. Results indicate that clinical
judgment and patient symptoms, not just Hb value, were used in decisions to
prescribe PRBC transfusions.
PMID- 29349624
TI - Combined effects of aspirin and vitamin D3 on two OSCC cell lines: a preliminary
study.
AB - OBJECTIVES: We evaluated the potential effects of aspirin combined with vitamin
D3 on cell proliferation and apoptosis in oral cancer cells. RESULTS: Compared to
the untreated control or individual drug, the combinations of aspirin and vitamin
D3 significantly decreased the rates of cell proliferation by CCK-8 assay, and
caused higher rates of cell apoptosis in both CAL-27 and SCC-15 cells by Annexin
V-FITC apoptosis assay and flow cytometry. Remarkably, the combined treatment
with aspirin and vitamin D3 significantly suppressed the expression of Bcl-2
protein and p-Erk1/2 protein, examined by western blot analysis. CONCLUSIONS: Our
study demonstrates that aspirin and vitamin D3 have biological activity against
two human OSCC cell lines and their activity is synergistic or additive when two
drugs used in combination with therapeutic concentrations. The combination of
aspirin and vitamin D3 may be an effective approach for inducing cell death in
OSCC.
PMID- 29349623
TI - The association between Toxoplasma gondii infection and hypertensive disorders in
T2DM patients: a case-control study in the Han Chinese population.
AB - Type 2 diabetes mellitus (T2DM) is a major global health problem. The rate of
infection with Toxoplasma gondii (T. gondii) is more than one-third of the total
world population. The effects of T. gondii infection on the risk of diabetic
complications and comorbidities are unclear. This study aims to determine the
relationship between T. gondii infection and complications of T2DM in the Han
Chinese population. We collected 1580 blood samples from T2DM patients and
measured the levels of specific IgG antibodies against T. gondii in the sera of
these patients using an ELISA assay. A logistic regression analysis was performed
to estimate the effect of T. gondii infection on the complications of T2DM, while
adjusting for age, gender, and triglyceride level (TG). We applied the
multifactor dimensionality reduction (MDR) method to detect the interactions
between T. gondii infections, demographic indexes and biochemical indicators
among the different complications. Gender (the odds ratio (OR) = 0.63, 95%CI
=0.45-0.89, P = 0.008) and TG level (OR = 0.64, 95%CI =0.45-0.89, P = 0.009) were
influencing factors in T. gondii infections. T2DM patients who were infected with
T. gondii had a 2.34 times risk of developing hypertension than those patients
without T. gondii infection (OR = 2.34, 95%CI = 1.12-4.88, P = 0.024). The
multiplicative interaction analysis and the additive interaction analysis did not
reveal any evidence of interactive effects on diabetic complications and
comorbidities. T. gondii might be a factor associated with hypertension in T2DM
patients.
PMID- 29349625
TI - Enhancement of the thermal and alkaline pH stability of Escherichia coli lysine
decarboxylase for efficient cadaverine production.
AB - OBJECTIVE: To enhance the thermal and alkaline pH stability of the lysine
decarboxylase from Escherichia coli (CadA) by engineering the decameric interface
and explore its potential for industrial applications. RESULTS: The mutant T88S
was designed for improved structural stability by computational analysis. The
optimal pH and temperature of T88S were 7.0 and 55 degrees C (5.5 and 50
degrees C for wild-type). T88S showed higher thermostability with a 2.9-fold
increase in the half-life at 70 degrees C (from 11 to 32 min) and increased
melting temperature (from 76 to 78 degrees C). Additionally, the specific
activity and pH stability (residual activity after 10 h incubation) of T88S at pH
8.0 were increased to 164 U/mg and 78% (58 U/mg and 57% for wild-type). The
productivity of cadaverine with T88S (284 g L-lysine L-1 and 5 g DCW L-1) was 40
g L-1 h-1, in contrast to 28 g L-1 h-1 with wild-type. CONCLUSION: The mutant
T88S showed high thermostability, pH stability, and activity at alkaline pH,
indicating that this mutant is a promising biocatalyst for industrial production
of cadaverine.
PMID- 29349626
TI - A two-stage system coupling hydrolytic acidification with algal microcosms for
treatment of wastewater from the manufacture of acrylonitrile butadiene styrene
(ABS) resin.
AB - OBJECTIVES: To demonstrate the effectiveness of a novel two-stage system coupling
hydrolytic acidification with algal microcosms for the treatment of acrylonitrile
butadiene styrene (ABS) resin-manufacturing wastewater. RESULTS: After hydrolytic
acidification, the BOD5/COD ratio increased from 0.22 to 0.56, showing improved
biodegradability of the wastewater. Coupled with hydrolytic acidification, the
algal microcosms showed excellent capability of in-depth removal of COD, NH3-N
and phosphorus with removal rates 83, 100, and 89%, respectively, and aromatic
pollutants, including benzene, were almost completely removed. The biomass
concentration of Chlorella sp. increased from 5 * 106 to 2.1 * 107 cells/ml after
wastewater treatment. CONCLUSIONS: This two-stage coupling system achieved deep
cleaning of the benzene-containing petrochemical wastewater while producing
greater algae biomass resources at low cost.
PMID- 29349627
TI - Modeling and simulation of enzymatic gluconic acid production using immobilized
enzyme and CSTR-PFTR circulation reaction system.
AB - OBJECTIVES: Production of gluconic acid by using immobilized enzyme and
continuous stirred tank reactor-plug flow tubular reactor (CSTR-PFTR) circulation
reaction system. RESULTS: A production system is constructed for gluconic acid
production, which consists of a continuous stirred tank reactor (CSTR) for pH
control and liquid storage and a plug flow tubular reactor (PFTR) filled with
immobilized glucose oxidase (GOD) for gluconic acid production. Mathematical
model is developed for this production system and simulation is made for the
enzymatic reaction process. The pH inhibition effect on GOD is modeled by using a
bell-type curve. CONCLUSIONS: Gluconic acid can be efficiently produced by using
the reaction system and the mathematical model developed for this system can
simulate and predict the process well.
PMID- 29349628
TI - Serum Total Magnesium Level and its Correlation with Symptom Control in Children
with Mild Persistent Asthma.
AB - OBJECTIVES: To determine the prevalence of hypomagnesemia in children with mild
persistent asthma and to correlate the serum magnesium levels with symptom
control in the above children. METHODS: It was a cross sectional study carried
out from 1st April 2015 to 31st July 2016 at the department of Pediatrics, JIPMER
Hospital. Participants included six to 12-y-old children with mild persistent
asthma registered at childhood asthma clinic. Pulmonary function tests were done
in all children using Care fusion Jaeger spirometer. Symptom control was assessed
by childhood asthma control test questionnaire and the asthma control test
questionnaire (ACT) score. Serum magnesium was measured using photometric method.
Proportion of children with well controlled, partially controlled and poorly
controlled asthma, serum magnesium levels across the three levels of control and
correlation of serum magnesium level with ACT score and pulmonary function tests
were studied. RESULTS: The prevalence of hypomagnesemia in children with mild
persistent asthma was 5.6%. The median serum magnesium level was 2.0 mg/dl (IQR
1.9-2.1 mg/dL). As assessed by the ACT score, 66% had well controlled, 23% had
partially controlled and 11% had poorly controlled asthma. There was no
significant difference in the serum magnesium levels in the above three groups.
There was no significant correlation between serum magnesium levels and ACT score
as well as pulmonary function tests. CONCLUSIONS: The prevalence of
hypomagnesemia in the index study is much lower than earlier studies and there
seems to be no significant association between serum magnesium levels and asthma
symptom control.
PMID- 29349629
TI - Cerebellum: from Development to Disease-the 8th International Symposium of the
Society for Research on the Cerebellum and Ataxias.
AB - In recent years, there has been tremendous growth in research on cerebellar motor
and non-motor functions. Cerebellum is particularly involved in the spectrum of
neurodevelopmental diseases. The 8th International Symposium of the Society for
Research on the Cerebellum and Ataxia (SRCA) was held in Winnipeg, Manitoba,
(Canada) on May 24-26, 2017. The main theme of the 8th International Symposium
was "Development of the Cerebellum and Neurodevelopmental Disorders." Advances in
genetics, epigenetic, cerebellar neurogenesis, axonogenesis and gliogenesis,
cerebellar developmental disorders including autism spectrum disorders (ASD),
neuroimaging, cerebellar ataxias, medulloblastoma, and clinical investigation of
cerebellar diseases were presented. The goal of this symposium was to provide a
platform to discuss cutting-edge knowledge while allowing researchers and
trainees the opportunity to share and discuss their front-line research and ideas
with others in the field, make connections, and strengthen international
collaborations. The Ferdinando Rossi lecture was delivered by Dr. Richard Hawkes
on the topic of patterning of the cerebellar cortex. This symposium emphasized
the major importance of the involvement of the cerebellum in neurodevelopmental
diseases from the clinical, radiological, biological, and genetic standpoint.
PMID- 29349630
TI - Developmental Changes in Serotonergic Modulation of GABAergic Synaptic
Transmission and Postsynaptic GABAA Receptor Composition in the Cerebellar
Nuclei.
AB - Outputs from the cerebellar nuclei (CN) are important for generating and
controlling movement. The activity of CN neurons is controlled not only by
excitatory inputs from mossy and climbing fibers and by gamma-aminobutyric acid
(GABA)-based inhibitory transmission from Purkinje cells in the cerebellar cortex
but is also modulated by inputs from other brain regions, including serotonergic
fibers that originate in the dorsal raphe nuclei. We examined the modulatory
effects of serotonin (5-HT) on GABAergic synapses during development, using rat
cerebellar slices. As previously reported, 5-HT presynaptically decreased the
amplitudes of stimulation-evoked inhibitory postsynaptic currents (IPSCs) in CN
neurons, with this effect being stronger in slices from younger animals
(postnatal days [P] 11-13) than in slices from older animals (P19-21). GABA
release probabilities accordingly exhibited significant decreases from P11-13 to
P19-21. Although there was a strong correlation between the GABA release
probability and the magnitude of 5-HT-induced inhibition, manipulating the
release probability by changing extracellular Ca2+ concentrations failed to
control the extent of 5-HT-induced inhibition. We also found that the IPSCs
exhibited slower kinetics at P11-13 than at P19-21. Pharmacological and molecular
biological tests revealed that IPSC kinetics were largely determined by the
prevalence of alpha1 subunits within GABAA receptors. In summary, pre- and
postsynaptic developmental changes in serotonergic modulation and GABAergic
synaptic transmission occur during the second to third postnatal weeks and may
significantly contribute to the formation of normal adult cerebellar function.
PMID- 29349631
TI - Promoter analysis of the fish gene of slow/cardiac-type myosin heavy chain
implicated in specification of muscle fiber types.
AB - Vertebrate skeletal muscles consist of heterogeneous tissues containing various
types of muscle fibers, where specification of the fiber type is crucial for
muscle development. Fish are an attractive experimental model to study the
mechanisms of such fiber type specification because of the separated localization
of slow and fast muscles in the trunk myotome. We examined regulation of
expression of the torafugu gene of slow/cardiac-type myosin heavy chain, MYH M5 ,
and isolated an operational promoter in order to force its tissue-specific
expression across different fish species via the transgenic approach in zebrafish
and medaka. This promoter activity was observed in adaxial cell-derived
superficial slow muscle fibers under the control of a hedgehog signal. We also
uncovered coordinated expression of MYH M5 and Sox6b, which is an important
transcriptional repressor for specification of muscle fiber types and
participates in hedgehog signaling. Sequence comparison in the 5'-flanking region
identified three conserved regions, CSR1-CSR3, between torafugu MYH M5 and its
zebrafish ortholog. Analysis of deletion mutants showed that CSR1 significantly
stimulates gene expression in slow muscle fibers. In contrast, deletion of CSR3
resulted in ectopic expression of a reporter gene in fast muscle fibers. CSR3 was
found to contain a putative Sox family protein-binding site. These results
indicate that the dual mechanism causing inhibition in fast muscle fibers and
activation in slow muscle fibers is essential for slow muscle fiber-specific gene
expression in fish.
PMID- 29349632
TI - Growth performance and protective effect of vitamin E on oxidative stress
pufferfish (Takifugu obscurus) following by ammonia stress.
AB - This study was conducted to determine the effects of vitamin E on growth
performance, biochemical parameters, and antioxidant capacity of pufferfish
(Takifugu obscurus) exposed to ammonia stress. The experimental basal diets
supplemented with vitamin E at the rates of 2.31 (control), 21.84, 40.23, 83.64,
158.93, and 311.64 mg kg-1 dry weight were fed to fish for 60 days. After the
feeding trial, the fish were exposed to 100 mg L-1 ammonia-nitrogen for 48 h. The
results shown that the vitamin E group significantly improved weight gain,
specific growth rate, and the expression levels of growth hormone receptors and
insulin-like growth factor. Fish fed with the vitamin E-supplemented diets could
increase plasma alkaline phosphatase activities and decrease plasma
glutamicoxalacetic transaminase and glutamic-pyruvic transaminase activities. The
relative expression levels of heat shock proteins (40.23-311.64 mg kg-1 vitamin E
diet group), manganese superoxide dismutase (83.64-158.93 mg kg-1 vitamin E diet
group), catalase (40.23-311.64 mg kg-1 vitamin E diet group), and glutathione
reductase (40.23-311.64 mg kg-1 vitamin E diet group) were upregulated. On the
other hand, the decreased level of reactive oxygen species (ROS) was observed in
the 83.64-311.64 mg kg-1 vitamin E additive group. These results showed that
vitamin E might have a potentially useful role as an effective antioxidant to
improve resistance in pufferfish.
PMID- 29349634
TI - Donor Cell-Derived Chronic Myeloproliferative Disease with t(7;11)(p15;p15) after
Cord Blood Transplantation in a Patient with Philadelphia Chromosome-Positive
Acute Lymphoblastic Leukemia.
AB - We report a case of donor cell-derived chronic myeloproliferative disease with
t(7;11)(p15;p15) occurring after cord blood transplantation (CBT). A 41-year-old
man developed precursor B-cell acute lymphoblastic leukemia with a karyotype of
46, XY, t(9;22)(q34;q11) and inv(9)(p11;q13), for which he received CBT from a
sex-mismatched donor at the first complete remission of the leukemia. Five months
after CBT, gradual neutrophilia of unknown origin developed following the myeloid
reconstitution after CBT. Karyotyping of bone marrow cells at 9 months after CBT
showed 46,XX, t(7;11)(p15;p15) in 17/20 dividing cells, but neither Philadelphia
chromosome (Ph) nor inv(9)(p11;q13) was present. This is the first report of
chronic myeloproliferative disease with t(7;11)(p15;p15) that developed in donor
cells after CBT. The donor was well-developed and healthy, at least at the time
of follow-up, half a year after the birth.
PMID- 29349633
TI - Effects of tetradecylthioacetic acid (TTA) treatment on lipid metabolism in
salmon hearts-in vitro and in vivo studies.
AB - In intensive farming of Atlantic salmon, a large proportion of observed mortality
is related to cardiovascular diseases and circulatory failure, indicating
insufficient robustness and inadequate cardiac performance. This paper reports on
the use of tetradecylthioacetic acid (TTA) where the main objective was to
enhance utilisation of fatty acids (FA), considered the main energy source of the
heart. In this study, three experiments were conducted: (I) an in vivo study
where salmon post-smolt were administrated dietary TTA in sea, (II) an in vitro
study where isolated salmon heart cells were pre-stimulated with increasing doses
of TTA and (III) an in vivo experiment where salmon post-smolt were subjected to
injections with increasing doses of TTA. In study I, TTA-treated fish had a
smaller decrease in heart weight relative to fish bodyweight (CSI) in a period
after sea transfer compared to the control. This coincided with lowered condition
factor and muscle fat in the TTA-treated fish, which may indicate a higher
oxidation of lipids for energy. In study II, the isolated hearts treated with the
highest dose of TTA had higher uptake of radiolabelled FA and formation of CO2
and acid-soluble products. In study III, expression of genes regulating
peroxisomal FA oxidation, cell growth, elongation and desaturation were
upregulated in the heart of TTA injected salmon. In contrast, genes involved in
FA transport into the mitochondria were not influenced. In conclusion, these
experiments indicate that TTA enhances energy production in salmon hearts by
stimulation of FA oxidation.
PMID- 29349635
TI - The diving reflex and asphyxia: working across species in physiological ecology.
AB - Beginning in the mid-1930s the comparative physiologists Laurence Irving and Per
Fredrik (Pete) Scholander pioneered the study of diving mammals, particularly
harbor seals. Although resting on earlier work dating back to the late nineteenth
century, their research was distinctive in several ways. In contrast to medically
oriented physiology, the approaches of Irving and Scholander were strongly
influenced by natural history, zoology, ecology, and evolutionary biology. Diving
mammals, they argued, shared the cardiopulmonary physiology of terrestrial
mammals, but evolution had modified these basic adaptive processes in extreme
ways. In particular, seals' remarkable ability to hold breath, lower metabolism,
produce energy anaerobically, and resist asphyxiation, provided a sharp contrast
with terrestrial mammals, including humans. This diving physiology was an extreme
elaboration of a general regulatory mechanism that allowed seals and other diving
mammals to remain active underwater for extended periods. The decrease in heart
rate referred to as bradycardia or the "diving reflex" was highly developed in
diving mammals, but also found in less developed form in many other organisms
faced by asphyxia. It therefore served as a kind of "master switch" for lowering
metabolism in diving, hibernation, parturition, drowning, and other physiological
responses involving lack of oxygen. Studying bradycardia unified a wide diversity
of physiological phenomena, while also providing a context for contrasting the
physiological responses of various species, including humans. Conducted in the
laboratory and the field, this research served as a bridge between a comparative
physiological ecology focused on non-human species and a human-centered general
physiology.
PMID- 29349636
TI - Effects of Asymmetric Local Joule Heating on Silicon Nanowire-Based Devices
Formed by Dielectrophoresis Alignment Across Pt Electrodes.
AB - We demonstrate the fabrication and characterization of silicon nanowire-based
devices in metal-nanowire-metal configuration using direct current
dielectrophoresis. The current-voltage characteristics of the devices were found
rectifying, and their direction of rectification could be determined by voltage
sweep direction due to the asymmetric Joule heating effect that occurred in the
electrical measurement process. The photosensing properties of the rectifying
devices were investigated. It reveals that when the rectifying device was in
reverse-biased mode, the excellent photoresponse was achieved due to the strong
built-in electric field at the junction interface. It is expected that rectifying
silicon nanowire-based devices through this novel and facile method can be
potentially applied to other applications such as logic gates and sensors.
PMID- 29349637
TI - Association between keeping home records of catheter exit-site and incidence of
peritoneal dialysis-related infections.
AB - PURPOSE: To prevent peritoneal dialysis (PD)-related infection, components of
self-catheter care have been emphasized. However, studies on the effectiveness of
home recording for the prevention of PD-related infections are limited. This
study aimed to examine the association between keeping home records of catheter
exit site and incidence of PD-related infections. METHODS: Home record books were
submitted by patients undergoing PD. The proportion of days on which exit-site
home recording was carried out for 120 days (0-100%) was obtained. The patients
were divided into the frequent home recording group (>= 40.5%; median value) and
the infrequent home recording group (< 40.5%). The associations between the
recording group and the incidence rate ratios (IRRs) of PD-related infections
were estimated via negative binomial regression models. RESULTS: A total of 67
patients participated in this study (mean age, 66.7 years). The incidence rates
for exit-site infection, tunnel infection, and peritonitis were 0.42, 0.22, and
0.06 times/patient-year, respectively. The IRRs of the frequent versus infrequent
home recording groups for PD-related infection were 1.58 (95% confidence interval
[CI], 0.72-3.46) in the univariate analysis and 1.49 (95% CI, 0.65-3.42) in the
multivariate analysis. The IRRs of the frequent versus infrequent home recording
groups for composite of surgery to create a new exit site and removal of PD
catheter were 0.55 (95% CI, 0.78-3.88) and 0.35 (95% CI, 0.06-1.99),
respectively. CONCLUSIONS: This study could not prove that keeping home records
of patients' catheter exit site is associated with a lower incidence of PD
related infections.
PMID- 29349638
TI - Innovation in 3D Echocardiographic Imaging.
AB - PURPOSE OF REVIEW: The purpose of this review is to detail three-dimensional
echocardiographic (3DE) innovations in pre-surgical planning of congenital heart
disease, guidance of catheter interventions such as fusion imaging, and
functional assessment of patients with congenital heart disease. RECENT FINDINGS:
Innovations in 3DE have helped us delineate the details of atrioventricular valve
function and understand the mechanism of atrioventricular valve failure in
patients with atrioventricular septal defect and single ventricle post repair.
Advancement in holographic display of 3D datasets allows for better manipulation
of 3D images in three dimensions and better understanding of anatomic
relationships. 3DE with fusion imaging reduces radiation in catheter
interventions and provides presentations of 3DE images in the similar fashion as
the fluoroscopic images to improve communication between cardiologists. Lastly,
3DE allows for quantitative ventricular volumetric and functional assessment.
Recent innovations in 3DE allow for pre-surgical planning for congenital heart
disease, reduce radiation using fusion imaging in catheter interventions, and
enable accurate assessment of ventricular volume and function without geometric
assumptions.
PMID- 29349640
TI - Medical Cytogenetics : Reviewed by Shinichi Misawa.
PMID- 29349641
TI - Thrombosis and Antithrombotic Therapy : Reviewed by Shinsaku Hirosawa.
PMID- 29349639
TI - Outcomes in syncope research: a systematic review and critical appraisal.
AB - Syncope is the common clinical manifestation of different diseases, and this
makes it difficult to define what outcomes should be considered in prognostic
studies. The aim of this study is to critically analyze the outcomes considered
in syncope studies through systematic review and expert consensus. We performed a
systematic review of the literature to identify prospective studies enrolling
consecutive patients presenting to the Emergency Department with syncope, with
data on the characteristics and incidence of short-term outcomes. Then, the
strengths and weaknesses of each outcome were discussed by international syncope
experts to provide practical advice to improve future selection and assessment.
31 studies met our inclusion criteria. There is a high heterogeneity in both
outcome choice and incidence between the included studies. The most commonly
considered 7-day outcomes are mortality, dysrhythmias, myocardial infarction,
stroke, and rehospitalisation. The most commonly considered 30-day outcomes are
mortality, haemorrhage requiring blood transfusion, dysrhythmias, myocardial
infarction, pacemaker or implantable defibrillator implantation, stroke,
pulmonary embolism, and syncope relapse. We present a critical analysis of the
pros and cons of the commonly considered outcomes, and provide possible solutions
to improve their choice in ED syncope studies. We also support global initiatives
to promote the standardization of patient management and data collection.
PMID- 29349643
TI - A congenitally hypothyroid young man (Seated Dwarf, Goya's Studio, 19th century).
PMID- 29349642
TI - Increased serum periostin concentrations are associated with the presence of
diabetic retinopathy in patients with type 2 diabetes mellitus.
AB - PURPOSE: To determine the association between serum periostin and the presence of
diabetic retinopathy (DR). METHODS: Serum periostin was detected in 114 healthy
subjects, 122 patients with type 2 diabetes mellitus (T2DM) and 159 patients with
DR and compared among groups. Clinical data and other laboratory measurements
such as glycated hemoglobin (HbA1c), lipid profiles, serum creatinine (Cr) and
high-sensitivity CRP (hsCRP) were also collected and compared among groups. For
subgroup analysis, patients with DR were divided into a non-proliferated diabetic
retinopathy (NPDR) group and a proliferated diabetic retinopathy (PDR) group.
Multivariate analysis was performed using logistic regression models. RESULTS:
The serum periostin level was significantly higher in patients with diabetic
retinopathy compared with healthy subjects and patients with T2DM (both P <
0.001, respectively). Also, the periostin level was significantly higher in the
PDR group compared to the NPDR group (P = 0.044). Multivariate logistic
regression revealed that serum periostin was independently associated with the
presence of DR in patients with T2DM (P < 0.001). The receiver operating
characteristic (ROC) curves for DR development using serum periostin showed that
the area under the receiver operating characteristic curves (AUC) was 0.838 (P <
0.001). CONCLUSIONS: The current study demonstrated that serum periostin is
significantly associated with the presence of DR in patients with T2DM and is an
independent risk factor of DR.
PMID- 29349644
TI - Does Statin Benefits Patients with Heart Failure Undergoing Percutaneous Coronary
Intervention? Findings from the Melbourne Interventional Group Registry.
AB - PURPOSE: The effectiveness of statins in improving clinical outcomes among
patients with heart failure (HF) undergoing percutaneous coronary intervention
(PCI) is unclear. We examined the association between use of statins and clinical
outcomes in patients with HF included in the Melbourne Interventional Group
registry. METHODS: Patients were followed from 30 days to 1 year post-PCI for a
primary composite outcome of all-cause mortality and hospitalisation for
cardiovascular (CV) causes. Secondary outcomes included major adverse cardiac
events (MACE, a composite of all-cause mortality, myocardial infarction and
target vessel revascularisation) and hospitalisation for CV causes. Outcomes were
compared between statin-treated and non-statin-treated patients (at 30 days post
PCI) using propensity scores to balance for risk factors. RESULTS: Among 991
patients included in the inverse probability-weighted Cox model, statin use had
no significant effect on the primary composite outcome [adjusted hazard ratio
(aHR), 1.03; 95% confidence interval (CI), 0.68 to 1.56; p = 0.89], nor MACE
(aHR, 0.99; 95% CI, 0.54 to 1.84; p = 0.99) or hospitalisation for CV causes (HR,
1.13; 95% CI, 0.74 to 1.72; p = 0.57). CONCLUSIONS: Our results suggest that
statin therapy may confer no significant benefits in patients with HF undergoing
PCI. However, prospective randomised controlled trials are needed to provide more
definitive answers.
PMID- 29349645
TI - The Incidence and the Prognostic Impact of Acute Kidney Injury in Acute
Myocardial Infarction Patients: Current Preventive Strategies.
AB - Acute kidney injury (AKI) is one of the most common complications during
hospitalization in various clinical settings. The goal of this review was to
assess the incidence of AKI in acute myocardial infarction patients (AMI), how
this incidence is affected by the diverse definitions, and if there is
variability in the reported rates over recent years. Additionally, we sought to
appraise the impact of AKI on short- and long-term prognosis of these patients.
Finally, we report on the current preventive measures as they are suggested in
the current guidelines of various societies, we comment on the evidence that
support them, and we review the literature for other proposed therapeutic
strategies, which either failed to prove their efficacy or they are not
adequately confirmed yet. Due to the heterogeneity in AKI definition and in the
population studied of the published data, the incidence of AKI ranged from 5.2 to
59%. A recent meta-analysis reported a median value of 15.8%. All studies
assessing AKI-related prognosis in AMI patients suggested that presence of AKI
has detrimental effect on patients prognosis, raising mortality two- to threefold
not only during the 30 first days but also during the first year after the acute
event. Various treatment modalities have been proposed for prevention of AKI in
AMI patients; however, the majority of them failed to prove their efficacy in the
clinical trial arena. Hydration, use of iso- or low-osmolar agents at the lowest
possible dose during coronary interventions, and use of statins have been
proposed among others. Nonetheless, the prevalence of AKI after an AMI still
remains high today and therefore it is crucial for the practicing physician to be
aware of its presence and for the scientific community to identify novel measures
for a more efficacious prevention.
PMID- 29349648
TI - Establishment of a Monosomy 7 Leukemia Cell Line, MONO-7, With aras Gene
Mutation.
AB - A monosomy 7 leukemia cell line, designated MONO-7, was established from the
peripheral blood of a patient with monosomy 7 acute myelocytic leukemia (French
American-British classification M0). The cells were cultured continuously for
more than 24 months in RPMI-1640 medium supplemented with 10% heat-inactivated
fetal calf serum. The cell line exhibits an unclassified appearance.
Cytochemically, alpha-naphthol-acetate esterase and myeloperoxidase are negative.
Immunophenotypi-cally, the cell line expresses CD33, CD13, CD56, CD34, CD38, HLA
DR, and CD45, but lacks T and B cell-associated antigens. Karyotypic analysis of
the cell line showed only 45,XY,-7. Analysis of the N-ras gene mutation
demonstrated identical mutations in fresh leukemic cells and the MONO-7 cell
line. Clonal rearrangements of the immunoglobulin heavy-chain gene, T-cell
receptor beta-chain gene, or T-cell receptor gamma-chain gene were not found in
DNA extracted from MONO-7 cells. The growth of MONO-7 cells in vitro was
stimulated by recombinant human granulocyte-macrophage colony-stimulating factor
or interleukin 3. To our knowledge, this is the first report of the establishment
of a cell line with the karyotype 45,XY,-7 with-out any other abnormality and
with a ras gene mutation.
PMID- 29349647
TI - Behaviour of freshwater snails (Radix balthica) exposed to the pharmaceutical
sertraline under simulated predation risk.
AB - Due to their potential for affecting the modulation of behaviour, effects of
selective serotonin reuptake inhibitors (SSRIs) in the environment are
particularly interesting regarding interspecies interactions and non-consumptive
effects (NCEs) induced by predator cues in prey organisms. We evaluated the
effects of sertraline (0.4, 40 ng/L, 40 ug/L) over 8 days on activity and habitat
choice in the freshwater snail Radix balthica, on snails' boldness in response to
mechanical stimulation (simulating predator attack), and their activity/habitat
choice in response to chemical cues from predatory fish. We hypothesised that
sertraline exposure would detrimentally impact NCEs elicited by predator cues,
increasing predation risk. Although there were no effects of sertraline on NCEs,
there were observed effects of chemical cue from predatory fish on snail
behaviour independent of sertraline exposure. Snails reduced their activity in
which the percentage of active snails decreased by almost 50% after exposure to
fish cue. Additionally, snails changed their habitat use by moving away from open
(exposed) areas. The general lack of effects of sertraline on snails' activity
and other behaviours in this study is interesting considering that other SSRIs
have been shown to induce changes in gastropod behaviour. This raises questions
on the modes of action of various SSRIs in gastropods, as well as the potential
for a trophic "mismatch" of effects between fish predators and snail prey in
aquatic systems.
PMID- 29349649
TI - Structure-activity relationships of flavanones, flavanone glycosides, and
flavones in anti-degranulation activity in rat basophilic leukemia RBL-2H3 cells.
AB - The incidence of type I allergies, which are associated with mast cell
degranulation and local inflammation, is increasing, and new treatments are
needed. To date, structure-activity relationships of flavonoids in their
degranulation-inhibiting activity have not been systematically characterized. In
the current study, the degranulation-inhibiting activity of a series of
flavonoids was evaluated. The following three observations were made: (1) the
activity disappears when a sugar moiety is introduced into the A ring of the
flavanone; (2) the activity depends on the number of hydroxyl groups on the B
ring; (3) the activity is markedly enhanced when a double bond is introduced into
the C ring. The information obtained in the current study may guide the
development of a therapy for type I allergies.
PMID- 29349652
TI - Social Factors Associated with Non-initiation and Cessation of Predominant
Breastfeeding in a Mother-Child Cohort in Spain.
AB - Objective The aim of the study was to identify factors associated with non
initiation and cessation of predominant breastfeeding (PBF) in a mother-child
cohort from Spain. Materials and Methods The analysis included 2195 mother-infant
from birth to 14 months post- delivery recruited between 2004 and 2008. Maternal
characteristics were collected during the pregnancy. Lactation data were obtained
at 6 and 14 months after delivery. PBF was defined as intake of breast milk plus
liquids like juices or water. The PBF cessation was calculated using the date
that women started PBF and the date that she reported to start giving infant
formula and/or food. The relationship between maternal variables and PBF
initiation and cessation was modeled using logistic and Cox proportional hazards
regression analysis. Results The prevalence of PBF at hospital discharge was
85.3, 53.4% at 3 months, 46.1% at 4 months and 7.2% at 6 month. Only two women
continued PBF at 12 months and none at 14 months. The initiating of PBF was
associated with higher levels of maternal education, being a first-time mother
and worked in a non-manual occupation. Higher level of physical activity, not
smoking and having a healthy BMI, were also positively associated with PBF
initiation. PBF cessation was higher in young, obese women, who had had
complications during the pregnancy, and who had lower levels of education and
smoked. The employment status of women, in week 32 of pregnancy and also in month
14 post-delivery, determined likelihood of PBF cessation. Conclusions Healthier
habits and education positively influenced PBF initiation and duration. Decrease
in PBF duration rates in Spain can be interpreted in part as a consequence of
women returning to work.
PMID- 29349651
TI - Epidemiology of Head Injuries Focusing on Concussions in Team Contact Sports: A
Systematic Review.
AB - BACKGROUND: Although injuries to the head represent a small proportion of all
sport injuries, they are of great concern due to their potential long-term
consequences, which are even suspected in mild traumatic brain injuries.
OBJECTIVE: The aim of this review was to compare the incidence of concussions and
other head injuries in elite level football, rugby, ice hockey and American
Football. METHODS: Four electronic databases (CINAHL, PsycINFO, Web of Science,
PubMed) were searched. Prospective cohort studies on the incidence of concussion
in elite athletes aged 17 years or older that were published in an English
language peer-reviewed journal since 2000 were included. Two authors
independently evaluated study eligibility and quality. The extracted data on
concussions were pooled in a meta-analysis using an inverse-variance fixed
effects model. The extracted data on head injuries were reported in a narrative
and tabular summary. RESULTS: The search yielded 7673 results of which 70
articles were included in the qualitative and 47 in the quantitative analysis. In
our meta-analysis, we found the highest concussion incidences in rugby match play
(3.89 and 3.00 concussions per 1000 h and athletic exposures (AEs),
respectively), and the lowest in men's football training (0.01 and 0.08 per 1000
h and AEs, respectively). Overall, concussions and all head injuries were rare in
training when compared to match play. Female players had an increased concussion
risk in football and ice hockey when compared to male players. CONCLUSION: Future
research should focus on concussion in women's contact sports, as there is little
evidence available in this area. Methodological deficits are frequent in the
current literature, especially regarding sample size and study power, and should
be avoided.
PMID- 29349653
TI - Exploring the Experiences of Middle Income Mothers in Practicing Exclusive
Breastfeeding in Nairobi, Kenya.
AB - Objectives To establish exclusive breastfeeding (EBF) practice, women are
encouraged to initiate breastfeeding of their newborns within one hour of
delivery and breastfeed exclusively for the first 6 months of the infant's life.
Research in Kenya has shown evidence of a reduced rate of EBF with an increase in
socio-economic class (SES). This study explores the experiences of middle-income
women so as to understand their attitudes and practices of EBF and to contribute
toward the Baby Friendly Hospital (BFHI) and Baby Friendly Community Initiatives
(BFCI) programs in Kenya. Methods A qualitative study using nine in-depth
interviews and two focus group discussions were conducted with middle-income
women with a child < 2 years. Thematic content analysis was used to analyze the
data. Results The majority of the women interviewed did not achieve EBF and this
was attributed to many challenges that they encountered such as; inadequate
workplace support including short maternity leave, lack of designated breast
feeding facilities flexible hours and breastfeeding breaks. Support structures
were highlighted as either inadequate or lacking while the internet was preferred
by most of the women for breastfeeding information. Mass media was seen as more
credible, though some women indicated that there was lack of depth in the
information it provided. Conclusion The study showed that majority of women were
unable to EBF for the first 6 months. Women experienced inadequate social,
healthcare and workplace support and preferred online sites for information on
breastfeeding than the healthcare professionals or mass media. Recommendation
There is need to implement policies at the workplace that promote a breastfeeding
friendly environment. There is also a need for more research on role of mass
media in promotion of optimal breastfeeding practices, especially how to reach
this population. There is a need for continued advocacy on social support
including spousal, relatives, and other community members at the community level.
PMID- 29349654
TI - The Role of Mentors in Early Intervention Referrals: Overlooked Views of
Pediatric Residency Training Directors.
AB - Objectives There continues to be a pressing need to increase referrals to family
centered early intervention (EI) for more eligible infants and toddlers with
inadequate consideration for the role of senior, mentoring professionals. Methods
To address a dearth in our understanding, a subset of Pediatric Residency
Training Directors shared views on EI, referral, and relevant training efforts.
Results Participating directors primarily reported limited understanding of EI.
Greater knowledge of family-focused EI correlated with its perceived helpfulness
(r = .420; p = .021), which positively correlated with referring a child to EI.
Despite 67% of the sample viewing pediatricians as 'most important' in screenings
and EI referrals, residents were perceived as only somewhat aware of EI referral
and services, and only somewhat aware of differences between clinic options and
Part C EI. Although nearly all respondents noted minimal EI exposure during
training, only 43% felt this amount was 'inadequate/insufficient'. The sample was
fairly evenly divided in being 'extremely' or 'somewhat' interested in
communicating with state EI leaders. Conclusions for Practice This preliminary
analysis describes perceptions among senior medical professionals who may
influence referrals via mentoring, training, and interdisciplinary collaboration.
Findings inform next steps in terms of research, improving education for
directors and residents, and collaborative information-sharing to bolster family
centered EI referrals to improve child and family outcomes.
PMID- 29349655
TI - Total body irradiation tremendously impair the proliferation, differentiation and
chromosomal integrity of bone marrow-derived mesenchymal stromal stem cells.
AB - Total body irradiation (TBI) is frequently used in hematopoietic stem cell
transplantation (HSCT) and is associated with many complications due to radiation
injury to the normal cells, including normal stem cells. Nevertheless, the
effects of TBI on the mesenchymal stromal stem cell (MSC) are not fully
understood. Bone marrow-derived MSCs (BM-MSCs) isolated from normal adults were
irradiated with 200 cGy twice daily for consecutive 3 days, a regimen identical
to that used in TBI-conditioning HSCT. The characteristics, differentiation
potential, cytogenetics, hematopoiesis-supporting function, and carcinogenicity
of the irradiated BM-MSCs were then compared to the non-irradiated control. The
irradiated and non-irradiated MSCs shared similar morphology, phenotype, and
hematopoiesis-supporting function. However, irradiated MSCs showed much lower
proliferative and differentiative potential. Irradiation also induced clonal
cytogenetic abnormalities of MSCs. Nevertheless, the carcinogenicity of
irradiated MSCs is low in vitro and in vivo. In parallel with the ex vivo
irradiation experiments, decreased proliferative and differentiative abilities
and clonal cytogenetic abnormalities can also be found in MSCs isolated from
transplant recipients who had received TBI-based conditioning previously. Thus,
TBI used in HSCT drastically injury MSCs and may contribute to the development of
some long-term complications associated with clonal cytogenetic abnormality and
poor adipogenesis and osteogenesis after TBI.
PMID- 29349656
TI - Correlations among multifocal electroretinography and optical coherence
tomography findings in patients with Parkinson's disease.
AB - To assess the correlation between functional and anatomical evaluations with
multifocal electroretinography (mfERG) and spectral-domain optical coherence
tomography (SD-OCT) in patients with Parkinson's disease (PD). This cross
sectional study involved 116 eyes of 58 patients with PD and 30 age- and sex
matched control subjects. All study participants underwent a comprehensive neuro
ophthalmic examination, retinal single-layer thicknesses and volumes, and
peripapillary retinal nerve fiber layer (pRNFL) measurements with SD-OCT, and the
patients' mfERG recordings were evaluated. The macular retinal nerve fiber layer
(mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), outer nuclear
layer (ONL), retinal pigment epithelium (RPE), and photoreceptor layer (PR)
thicknesses, and mRNFL, RPE, and PR volumes were found lower in PD compared to
those of controls, while outer plexiform layer (OPL) volumes were increased (p <
0.05). We found delayed implicit times and decreased amplitudes in the mfERG of
PD patients versus those in control subjects (p < 0.05). We found significant
correlations between outer macular volumes, PR thicknesses, and N1 amplitudes of
rings 2 and 3and P1 amplitudes of rings 3, 4, and 5. Our study revealed thinning
of both inner and outer retinal single layers, increased OPL volume, and delayed
implicit times and decreased amplitudes in the mfERG of PD patients versus
control subjects and correlation between structural and functional parameters.
Our findings point out that SD-OCT and mfERG could both serve as non-invasive
tools for evaluating ophthalmic manifestations of Parkinson's disease.
PMID- 29349657
TI - Association between TBK1 mutations and risk of amyotrophic lateral
sclerosis/frontotemporal dementia spectrum: a meta-analysis.
AB - Recently, mutations in TBK1 (TANK-binding kinase 1) have been reported to be a
cause of amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD)
spectrum, but the relationship between them remains unclear owing to the small
sample size and low mutation rate. Therefore, we performed a two-stage meta
analysis to investigate the frequency of TBK1 mutations in ALS/FTD patients and
the association between the mutations and risk of ALS/FTD spectrum. In the first
stage, 12 studies involving 4173 ALS/FTD patients were included. The frequencies
of loss of function (LoF) and missense mutations were 1.0% (95% CI 0.6-1.7%) and
1.8% (95% CI 0.9-3.4%) in ALS/FTD patients respectively. Subgroup analysis
suggested a higher prevalence of TBK1 mutations in European patients than that in
Asian patients. In the second stage, 7 studies involving 3146 cases and 4856
controls were enrolled. Results showed that TBK1 LoF mutations were associated
with a significant increased risk for ALS/FTD spectrum (OR 11.78; 95% CI 4.21
33.00; p < 0.0001), while TBK1 missense mutations were associated with a
moderately increased susceptibility for ALS/FTD spectrum (OR 1.62; 95% CI 1.19
2.19; p = 0.002). In conclusion, TBK1 LoF and missense mutations are not
frequently found in ALS/FTD patients, and both of them are associated with an
increased risk for ALS/FTD spectrum.
PMID- 29349658
TI - The IL-10-producing regulatory B cells (B10 cells) and regulatory T cell subsets
in neuromyelitis optica spectrum disorder.
AB - B cells contribute to the pathogenesis of neuromyelitis optica (NMO) by producing
Aquaporin 4-specific autoantibodies (AQP4-ab); on the other hand, there are
certain B cells that suppress immune responses by producing regulatory cytokines,
such as IL-10. In this study, we investigated the presence of IL-10-producing
Breg cells among lymphocyte subsets. Twenty-two seropositive NMO spectrum
disorder (NMOSD) patients (29 samples) and 13 healthy controls (HCs) (14 samples)
were enrolled. All NMOSD patients have received one or more immunosuppressive
drugs. The phenotype and frequency of B cell and T cell subsets in the peripheral
blood were measured by flow cytometry. We defined Breg cells as IL-10-producing B
(B10) cells, which are CD19+CD39+CD1d+IL-10+. The potential relations were
evaluated between specific lymphocyte subsets and AQP4-ab intensity measured by
the cell-based indirect immunofluorescence assay. The frequency of B10 cells was
higher in patients with NMOSD regardless of the disease status than that in HCs
(attack samples; p = 0.009 and remission samples; p < 0.001, respectively). In
addition, the frequency of IL-17+ Treg cells among Treg cells was higher during
remission than during an attack (uncorrected p = 0.032). Among the lymphocyte
subsets, B10 cells alone showed a positive correlation with the intensity of AQP4
ab positivity (rho [rho] = 0.402 and p = 0.031). It was suggested that the
suppressive subsets including B10 and IL-17+ Treg cells might have important
roles in controlling disease status in NMOSD. Further functional studies may help
to elucidate the immunological role of B10 and IL-17+ Treg cells in NMOSD.
PMID- 29349659
TI - [Self- and informant-rating mood scales applied in elderly persons with
Alzheimer's dementia, with or without a language disorder].
AB - INTRODUCTION: Alzheimer's Dementia (AD) may be associated with symptoms of
depression. In AD, problems of language expression or understanding will arise
sooner or later. The aim of this study was to determine whether elderly persons
with AD, with or without a language disorder, experience difficulties
understanding and answering mood related questions. In addition to this, it was
our object to test the validity of the answers of nurses as informants, on the
mood of an elderly client. METHODS: 53 elderly persons, living in care homes, and
their nurses, took part in the study. 25 participants had been diagnosed with
Alzheimer's disease, 28 participants had no cognitive impairment. Language skills
were tested using the SAN-test (Stichting Afasie Nederland) and subtests of the
Aachen Aphasia Test (AAT). Mood was assessed with the Beck Depression Inventory
second edition (BDI-II-NL) and the Geriatric Depression Scale (GDS-30). RESULTS:
There were no significant differences in scores on the mood related
questionnaires between participants without cognitive impairment and participants
with Alzheimer's disease, with or without a language disorder. The correlation
between self- and informant-rating was very limited. In general, nurses reported
more depressive symptoms than the elderly persons did themselves. Disparities
between self- and informant-ratings varied from informant scores overestimating
low self-ratings of depression to informant scores underestimating high self
ratings. CONCLUSION: Alzheimer's disease, whether or not it is complicated by a
language disorder, does not disturb the normal score distribution on either test
(BDI or GDS). This means that elderly persons with Alzheimer's disease are
capable of adequately answering questions related to their own mood. However,
considerable discrepancies were found between observer- and self-ratings of
emotional wellbeing. Therefore it is important to not only take into account the
information of an informant when testing for depression, but also the elderly
person's own assessment of their mood.
PMID- 29349660
TI - Progestogen Hypersensitivity.
AB - PURPOSE OF REVIEW: Progestogen hypersensitivity (PH) is a rare disorder which
usually occurs in women of childbearing age with symptoms ranging from urticaria
with or without angioedema, multiple organ involvement consistent with allergic
anaphylaxis, to a spectrum of other non-evanescent skin eruptions. In this
review, we present a clinical vignette of PH and discuss the clinical
presentation and proposed pathomechanisms, diagnosis, and treatment of PH. RECENT
FINDINGS: The hypersensitivity symptoms are associated with exogenous progestin
exposure (e.g., contraceptive medicines, in vitro fertilization therapy) or
endogenous progesterone from progesterone surges during the luteal phase of the
menstrual cycle and pregnancy. Recognition of this condition can be challenging
to the clinician due to its heterogeneous clinical presentation. It has been
recently proposed to use the new term "progestogen hypersensitivity" to replace
"autoimmune progesterone dermatitis" due to the lack of evidence supporting an
autoimmune mechanism for this disorder. In addition, diagnostic and treatment
algorithms are now available that can lead to successful management of this
condition. More new developments of Progesterone desensitization protocols are
now available which appear to be the safest and most effective long-term
treatment option for PH. With the extensive use of oral contraceptives and
increased use of supra-physiologic doses of progesterone to support pregnancy in
in vitro fertilization, there is likely to be a higher prevalence of PH in the
future than currently recognized. Therefore, the allergist-immunologist will be
required to collaborate with gynecologists and reproductive endocrinologists to
diagnose and treat this condition.
PMID- 29349661
TI - PKM2 is involved in neuropathic pain by regulating ERK and STAT3 activation in
rat spinal cord.
AB - BACKGROUND: Pyruvate kinase isozymes M2 (PKM2), as a member of pyruvate kinase
family, plays a role of glycolytic enzyme in glucose metabolism. It also
functions as protein kinase in cell proliferation, signaling, immunity, and gene
transcription. In this study, the role of PKM2 in neuropathic pain induced by
chronic constriction injury (CCI) was investigated. METHODS: Rats were randomly
grouped to establish CCI models. PKM2, extracellular regulated protein kinases
(EKR), p-ERK, signal transducers and activators of transcription (STAT3), p
STAT3, phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and p-PI3K/AKT
proteins expression in spinal cord was examined by Western blot analysis.
Cellular location of PKM2 was examined by immunofluorescence. Knockdown of PKM2
was achieved by intrathecal injection of specific small interfering RNA (siRNA).
Von Frey filaments and radiant heat tests were performed to determine mechanical
allodynia and thermal hyperalgesia respectively. Lactate and adenosine
triphosphate (ATP) contents were measured by specific kits. Tumor necrosis factor
alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) levels were detected by ELISA
kits. RESULTS: CCI markedly increased PKM2 level in rat spinal cord. Double
immunofluorescent staining showed that PKM2 co-localized with neuron, astrocyte,
and microglia. Intrathecal injection of PKM2 siRNA not only attenuated CCI
induced ERK and STAT3 activation, but also attenuated mechanical allodynia and
thermal hyperalgesia induced by CCI. However, PKM2 siRNA failed to inhibit the
activation of AKT. In addition, PKM2 siRNA significantly suppressed the
production of lactate and pro-inflammatory mediators. CONCLUSION: Our findings
demonstrate that inhibiting PKM2 expression effectively attenuates CCI-induced
neuropathic pain and inflammatory responses in rats, possibly through regulating
ERK and STAT3 signaling pathway.
PMID- 29349663
TI - Ibandronate metal complexes: solution behavior and antiparasitic activity.
AB - To face the high costs of developing new drugs, researchers in both industry and
academy are looking for ways to repurpose old drugs for new uses. In this sense,
bisphosphonates that are clinically used for bone diseases have been studied as
agents against Trypanosoma cruzi, causative parasite of Chagas disease. In this
work, the development of first row transition metal complexes (M = Co2+, Mn2+,
Ni2+) with the bisphosphonate ibandronate (iba, H4iba representing the neutral
form) is presented. The in-solution behavior of the systems containing iba and
the selected 3d metal ions was studied by potentiometry. Mononuclear complexes
[M(Hxiba)](2-x)- (x = 0-3) and [M(Hiba)2]4- together with the formation of the
neutral polynuclear species [M2iba] and [M3(Hiba)2] were detected for all studied
systems. In the solid state, complexes of the formula [M3(Hiba)2(H2O)4].6H2O were
obtained and characterized. All obtained complexes, forming [M(Hiba)]- species
under the conditions of the biological studies, were more active against the
amastigote form of T. cruzi than the free iba, showing no toxicity in mammalian
Vero cells. In addition, the same complexes were selective inhibitors of the
parasitic farnesyl diphosphate synthase (FPPS) enzyme showing poor inhibition of
the human one. However, the increase of the anti-T. cruzi activity upon
coordination could not be explained neither through the inhibition of TcFPPS nor
through the inhibition of TcSPPS (T. cruzi solanesyl-diphosphate synthase). The
ability of the obtained metal complexes of catalyzing the generation of free
radical species in the parasite could explain the observed anti-T. cruzi
activity.
PMID- 29349664
TI - Sparse Functional Identification of Complex Cells from Spike Times and the
Decoding of Visual Stimuli.
AB - We investigate the sparse functional identification of complex cells and the
decoding of spatio-temporal visual stimuli encoded by an ensemble of complex
cells. The reconstruction algorithm is formulated as a rank minimization problem
that significantly reduces the number of sampling measurements (spikes) required
for decoding. We also establish the duality between sparse decoding and
functional identification and provide algorithms for identification of low-rank
dendritic stimulus processors. The duality enables us to efficiently evaluate our
functional identification algorithms by reconstructing novel stimuli in the input
space. Finally, we demonstrate that our identification algorithms substantially
outperform the generalized quadratic model, the nonlinear input model, and the
widely used spike-triggered covariance algorithm.
PMID- 29349662
TI - Roles and maturation of iron-sulfur proteins in plastids.
AB - One reason why iron is an essential element for most organisms is its presence in
prosthetic groups such as hemes or iron-sulfur (Fe-S) clusters, which are notably
required for electron transfer reactions. As an organelle with an intense
metabolism in plants, chloroplast relies on many Fe-S proteins. This includes
those present in the electron transfer chain which will be, in fact, essential
for most other metabolic processes occurring in chloroplasts, e.g., carbon
fixation, nitrogen and sulfur assimilation, pigment, amino acid, and vitamin
biosynthetic pathways to cite only a few examples. The maturation of these Fe-S
proteins requires a complex and specific machinery named SUF (sulfur
mobilisation). The assembly process can be split in two major steps, (1) the de
novo assembly on scaffold proteins which requires ATP, iron and sulfur atoms,
electrons, and thus the concerted action of several proteins forming early acting
assembly complexes, and (2) the transfer of the preformed Fe-S cluster to client
proteins using a set of late-acting maturation factors. Similar machineries,
having in common these basic principles, are present in the cytosol and in
mitochondria. This review focuses on the currently known molecular details
concerning the assembly and roles of Fe-S proteins in plastids.
PMID- 29349665
TI - Following the correction of varus deformity of the knee through total knee
arthroplasty, significant compensatory changes occur not only at the ankle and
subtalar joint, but also at the foot.
AB - PURPOSE: This study aimed to assess radiological changes of the ankle joint,
subtalar joint and foot following the correction of varus deformity of the knee
with total knee arthroplasty (TKA). It was hypothesized that following the
correction of varus deformity by TKA, compensatory reactions would occur at the
subtalar joint in accordance with the extent of the correction. METHODS: For this
prospective study, 375 knees of patients who underwent TKA between 2011 and 2012
were enrolled. The varus angle of the knee, talar tilt of the ankle joint (TT),
ground-talar dome angle of the foot (GD), anterior surface angle of the distal
tibia and lateral surface angle of the distal tibia, heel alignment ratio (HR),
heel alignment angle (HA), and heel alignment distance (HD) were measured on
radiographs obtained pre-operatively and at post-operative 6 months. RESULTS: The
mean correction angle in varus deformity of the knee was 10.8 +/- 4.1 degrees .
TT and GD changed significantly from 0.4 +/- 1.9 degrees and 6.5 +/- 3.1 degrees
pre-operatively to 0.1 +/- 1.8 degrees and 0.2 +/- 2.1 degrees , respectively
(p = 0.007, p < 0.001). No correlation was found between the preop-postop
variance in mechanical axis of the lower extremity (MA) and TT, but there was a
strong correlation between the preop-postop variance in MA and GD (r = 0.701).
HR, HA and HD also changed significantly post-operatively, and the preop-postop
variance in MA showed correlations with the preop-postop variances in HR, HA and
HD (r = 0.206, - 0.348, and - 0.418). TT and the three indicators of hindfoot
alignment all shifted to varus whereas GD was oriented in valgus. CONCLUSION:
Following the correction of varus deformity of the knee through TKA, significant
compensatory changes occurred not only at the ankle and subtalar joints, but also
at the foot. The findings of this study are useful in predicting the orientation
of changes in the ankle and subtalar joints and the foot following TKA, and in
determining the sequence of surgery when both the ankle and knee have a problem.
In other words, changes in the parts of the lower extremity below the ankle joint
following the correction of varus deformity of the knee must be considered when
TKA is planned and performed. Patients who have problems at the ankle, subtalar,
and foot joints in addition to varus deformity of the knee are recommended to
undergo knee joint correction first. LEVEL OF EVIDENCE: II.
PMID- 29349666
TI - New Frontiers in Cancer Therapy: Monoclonal Antibody Therapy of Hematologic
Malignancies.
PMID- 29349667
TI - Comparison of Enalapril, Candesartan and Intralesional Triamcinolone in Reducing
Hypertrophic Scar Development: An Experimental Study.
AB - BACKGROUND: The purpose of this study was to compare the effects of oral
enalapril, an angiotensin-converting enzyme inhibitor (ACE-I), oral candesartan,
an angiotensin receptor blocker (ARB), and intralesional corticosteroid
treatments in reducing scar formation. METHODS: Twenty male rabbits were divided
into five study groups: A (sham), B (control), C (ACE-I), D (ARB) and E
(intralesional corticosteroid). The rabbit ear hypertrophic scar model was used.
The hypertrophic scars were photographed and analyzed with the program ImageJ
quantitatively to determine the degree of collagen fibers. The scar elevation
index (SEI) was calculated at the end of the 40th day. Tissue samples were
stained with hematoxylin and eosin and Masson's trichrome and examined under
light microscopy for the determination of fibroblast number, epithelization,
vascularization, inflammation and fibrosis. RESULTS: The SEI was the highest in
the control group with the highest number of fibroblasts under the epithelium. In
the steroid group, the SEI was significantly lower than both the ACE-I (p: 0.02)
and ARB (p: 0.001) groups. The density of type 1 collagen fibers was the lowest
in the control group, whereas type 3 collagen fibers were highest in that group.
The ACE-I and ARB groups were similar regarding densities of type 1 and type 3
collagen fibers. The density of type 1 collagen fibers was the highest in the
steroid group, whereas the density of type 3 collagen fibers was the lowest in
that group. CONCLUSIONS: Enalapril, candesartan and intralesional steroid
therapies were all effective in reducing scar tissue development; however,
enalapril and steroid groups revealed better results. NO LEVEL ASSIGNED: 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- 29349668
TI - Serum MMP-9 Diagnostics, Prognostics, and Activation in Acute Coronary Syndrome
and Its Recurrence.
AB - Matrix metalloproteinase (MMP)-9 is crucial in atherosclerotic plaque rupture and
tissue remodeling after a cardiac event. The balance between MMP-9 and endogenous
inhibitor, tissue inhibitors of matrix metalloproteinase 1 (TIMP-1), is important
in acute coronary syndrome (ACS). This is an age- and gender-matched case-control
study of ACS (N = 669). Patients (45.7%) were resampled after recovery, and all
were followed up for 6 years. The molecular forms of MMP-9 were investigated by
gelatin zymography. Diagnostically, MMP-9 and the MMP-9/TIMP-1 molar ratio were
associated with ACS (OR 5.81, 95% CI 2.65-12.76, and 4.96, 2.37-10.38). The MMP-9
concentrations decreased 49% during recovery (p < 0.001). The largest decrease of
these biomarkers between acute and recovery phase (DeltaMMP-9) protected the
patients from major adverse cardiac events, especially the non-fatal events. The
fatal events were associated with in vitro activatable MMP-9 levels (p = 0.028).
Serum MMP-9 and the MMP-9/TIMP-1 molar ratio may be valuable in ACS diagnosis and
prognosis. High serum MMP-9 activation potential is associated with poor
cardiovascular outcome.
PMID- 29349669
TI - Positive Correlation between Matrix Metalloproteinases and Epithelial-to
Mesenchymal Transition and its Association with Clinical Outcome in Bladder
Cancer Patients.
AB - Involvement of matrix metalloproteinases (MMPs) in the pathogenesis of urothelial
carcinoma elects them to be sensitive marker for clinical and prognostic
implications. MMPs regulate tumor growth and invasion by inducing epithelial-to
mesenchymal transition (EMT) which is characterized by the complex reprogramming
of epithelial cells and ultimately bring about major changes in the structural
organization of bladder urothelium. The present study has been undertaken to
evaluate the clinical relevance of MMPs in two distinct types of bladder cancer
disease. Expression analysis of MMPs namely MMP-2, MMP-7, MMP-9 and EMT markers
including epithelial marker, E-cadherin; mesenchymal markers, N-cadherin and
Vimentin; and EMT-activating transcriptional factors (EMT-ATFs), Snail, Slug,
Twist and Zeb was done in 64 cases of bladder tumor tissues [{Non-muscle invasive
bladder cancer (NMIBC): 35 cases} and {Muscle invasive bladder cancer (MIBC): 29
cases}] by real-time quantitative polymerase chain reaction (RT-qPCR).
Immunohistochemistry (IHC) staining was done in matched bladder tumor tissues to
evaluate the protein expression and localization of E-cadherin, N-cadherin,
Vimentin, Snail, and Slug. Our data showed overexpression of MMP-2, MMP-7 and MMP
9 at transcriptome level in 32.8%, 25% and 37.5% bladder tumor cases
respectively. These tumor tissues were examined for higher expression of
mesenchymal markers (N-cadherin and Vimentin) at mRNA and protein level and
exhibited statistical association with tumor stage and tumor grade (p = 0.02, p =
0.04, Mann-Whitney test). Significant statistical correlation in tumor tissues
with overexpressed MMPs has also been observed between gain of transcriptional
factors and weak expression of E-cadherin with tumor stage, grade, gender,
presence of hematuria and smoking history of the patients. Gene expression
patterns of EMT markers in bladder tumors with overexpressed MMPs and their
significant association with clinical profile validate the important role of MMPs
in the pathogenesis of urothelial carcinoma of bladder (UCB). Increased
expression of specific MMPs may affect several downstream EMT programs and thus
may improve its diagnostic and prognostic utility in clinical setting.
PMID- 29349670
TI - Working (longer than) 9 to 5: are there cardiometabolic health risks for young
Australian workers who report longer than 38-h working weeks?
AB - PURPOSE: The average Australian working week in middle-aged and older workers
exceeds government recommendations. Long working weeks are associated with poor
health outcomes; however, the relationship between long working weeks and health
in young Australian workers is unknown. METHODS: Data were drawn from the 22-year
follow-up of the Western Australian Pregnancy Cohort (Raine) Study in Perth,
Western Australia. Information was available from 873 young adults about working
hours per week, shift work and sleep duration. Blood samples provided measures of
cardiometabolic risk (CMR) factors. RESULTS: Almost one-third (32.8%) of young
workers reported > 38 h working weeks. This was commonly reported in mining and
construction industries for males; health and social assistance, mining and
retail trade industries for females. CMR factors including increased waist
circumference, higher fasting plasma glucose and reduced HDL cholesterol were
associated with > 38 h working weeks. These relationships were not moderated by
gender or by BMI for glucose and HDL cholesterol. Total sleep time was
significantly lower in both male and female workers reporting > 38 h working
weeks, but did not mediate the relationships seen with CMR factors. CONCLUSIONS:
These findings point to early associations between > 38 h working weeks and CMR
risk, and highlight the potential benefit of making young employees aware of the
health associations with working arrangements to reduce the longer-term
relationships seen with working hours and poor cardiometabolic health in
population studies.
PMID- 29349671
TI - Is Older Age Associated with Higher Self- and Other-Rated ASD Characteristics?
AB - Autism spectrum disorder (ASD) characteristics seem to abate over time, but
whether this protracts until late adulthood is largely unknown. We cross
sectionally investigated self- and other-reported ASD characteristics of adults
with (ASD: Nmax-self = 237, Nmax-other = 130) and without ASD (COM: Nmax-self =
198, Nmax-other = 148) aged 19-79 years. Within the ASD group, self-reported ASD
characteristics, and sensory sensitivities were highest in middle adulthood,
while age was not associated to empathy. Sex differences were also found.
However, age-and sex-related differences were not revealed by others and self-
and other-report were poorly concordant. These results show that ASD
characteristics in adulthood are differently perceived across age, sex, and
informants and suggest that it is important to repeatedly assess self-reported
ASD characteristics during adulthood.
PMID- 29349672
TI - STA-ACA bypass using the ipsilateral free STA graft as an interposition graft and
A3-A3 anastomosis for treatment of bilateral ACA steno-occlusive ischemia.
AB - BACKGROUND: Anterior cerebral artery (ACA)-related ischemia is a rare entity in
patients with atherosclerosis. Some surgical treatments are reported to date.
METHOD: We present the modification of intracranial-intracranial and intracranial
extracranial bypasses for symptomatic bilateral ACA steno-occlusive disease. The
A3-A3 bypass followed by the superficial temporal artery-ACA bypass using the
ipsilateral free superficial temporal artery graft is useful without harvesting
of the radial artery. CONCLUSION: Bilateral ACA steno-occlusive induced ischemia
can be treated with tailored bypass procedures.
PMID- 29349673
TI - Pharmacological dissection of the cellular mechanisms associated to the
spontaneous and the mechanically stimulated ATP release by mesentery endothelial
cells: roles of thrombin and TRPV.
AB - Endothelial cells participate in extracellular ATP release elicited by
mechanosensors. To characterize the dynamic interactions between mechanical and
chemical factors that modulate ATP secretion by the endothelium, we assessed and
compared the mechanisms participating in the spontaneous (basal) and mechanically
stimulated secretion using primary cultures of rat mesentery endothelial cells.
ATP/metabolites were determined in the cell media prior to (basal) and after cell
media displacement or a picospritzer buffer puff used as mechanical stimuli.
Mechanical stimulation increased extracellular ATP that peaked within 1 min, and
decayed to basal values in 10 min. Interruption of the vesicular transport route
consistently blocked the spontaneous ATP secretion. Cells maintained in media
lacking external Ca2+ elicited a spontaneous rise of extracellular ATP and
adenosine, but failed to elicit a further extracellular ATP secretion following
mechanical stimulation. 2-APB, a TRPV agonist, increased the spontaneous ATP
secretion, but reduced the mechanical stimulation-induced nucleotide release.
Pannexin1 or connexin blockers and gadolinium, a Piezo1 blocker, reduced the
mechanically induced ATP release without altering spontaneous nucleotide levels.
Moreover, thrombin or related agonists increased extracellular ATP secretion
elicited by mechanical stimulation, without modifying spontaneous release. In
sum, present results allow inferring that the spontaneous, extracellular
nucleotide secretion is essentially mediated by ATP containing vesicles, while
the mechanically induced secretion occurs essentially by connexin or pannexin1
hemichannel ATP transport, a finding fully supported by results from Panx1-/-
rodents. Only the latter component is modulated by thrombin and related receptor
agonists, highlighting a novel endothelium-smooth muscle signaling role of this
anticoagulant.
PMID- 29349675
TI - Saphenous vein graft percutaneous coronary intervention : A different kind of
animal.
PMID- 29349674
TI - Extracorporeal life support in cardiogenic shock: indications and management in
current practice.
AB - Veno-arterial extracorporeal life support (VA-ECLS) provides circulatory and
respiratory stabilisation in patients with severe refractory cardiogenic shock.
Although randomised controlled trials are lacking, the use of VA-ECLS is
increasing and observational studies repeatedly have shown treatment benefits in
well-selected patients. Current clinical challenges in VA-ECLS relate to optimal
management of the individual patient on extracorporeal support given its inherent
complexity. In this review article we will discuss indications, daily clinical
management and complications of VA-ECLS in cardiogenic shock refractory to
conventional treatment strategies.
PMID- 29349676
TI - Environment-Friendly Synthesis of Trace Element Zn, Sr, and F Codoping
Hydroxyapatite with Non-cytotoxicity and Improved Osteoblast Proliferation and
Differentiation.
AB - Hydroxyapatite (HAp, Ca10[PO4]6[OH]2) doped with numerous trace elements
possesses sensational biochemical effects in natural bones. To study the
biochemical function of Zn, Sr, and F elements, a series of neoteric HAp
biomaterials with Zn, Sr, and F concentrations close to natural bones are firstly
synthesized by one-pot hydrothermal method. These materials are characterized
through powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy
(FTIR), and scanning electron microscope (SEM). All the synthesized materials are
HAp phase. The morphology of these materials is nanorods. The phenomenon that
L929 cells can live even at 400 MUg/mL powder concentration indicates that these
materials are non-cytotoxic. The active effects of samples on proliferation and
differentiation of osteoblast cells (MC3T3-E1) are certified by MTT and alkaline
phosphatase (ALP) activity assays. The adhesion and proliferation of osteoblast
measurement manifest that amounts of MC3T3-E1 advances about 1.86 times for
ZnSrF/HAp compared with undoped HAp. This achievement may inspire us on the
artificial design of new-style bionic bone grafts using trace bioactive elements
and also suggest its latent applications in orthopedic surgery and bone
osseointegration.
PMID- 29349678
TI - Hughes Syndrome: Antiphospholipid Syndrome.
PMID- 29349677
TI - Mercuric Chloride Induced Ovarian Oxidative Stress by Suppressing Nrf2-Keap1
Signal Pathway and its Downstream Genes in Laying Hens.
AB - The present study evaluated the effects of mercury chloride (HgCl2) on follicular
atresia rate, sex hormone secretion, and ovarian oxidative stress in laying hens.
Antioxidant enzyme genes and the nuclear factor erythroid 2-related factor 2
(Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) signal pathway were further
studied to uncover the molecular mechanism. A total of 768 40-week-old Hy-Line
Brown laying hens were randomly allocated to four treatments with eight pens per
treatment and 24 hens of each pen. The birds were fed with four experimental
diets containing graded levels of mercury (Hg) at 0.280, 3.325, 9.415, and 27.240
mg/kg, respectively. Results revealed that a positive relationship occurred
between the accumulation of Hg in ovary and follicular atresia rate. Progesterone
(P4) level significantly decreased in all Hg-treatment groups (P < 0.05), and
follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were the
lowest in the 27.240-mg/kg Hg group. Besides, the activities of catalase (CAT),
superoxidative dismutase (SOD), glutathione reductase (GR), and glutathione (GSH)
content were significantly decreased in all Hg-treatment groups (P < 0.05).
Glutathione peroxidase (GSH-Px) activity significantly decreased, while
malondialdehyde (MDA) content sharply increased in the 27.240-mg/kg Hg group (P <
0.05). In addition, there were positive relationships between antioxidant enzyme
activities and antioxidant gene expressions or between antioxidant gene
expressions and Nrf2 mRNA expression, while negative correlations occurred
between Nrf2 and Keap1 at transcription and protein levels. It could be concluded
that Hg induced ovarian function disorders and ovarian oxidative stress by means
of impairing the Nrf2-Keap1 signal pathway in laying hens.
PMID- 29349679
TI - Autoimmune encephalitis associated with glutamic acid decarboxylase antibodies: a
case series.
AB - Antibodies against glutamic acid decarboxylase (GAD) are associated with various
neurologic conditions described in patients including stiff person syndrome,
cerebellar ataxia, refractory epilepsy, limbic and extralimbic encephalitis. GAD
antibodies-related limbic encephalitis cases are well described; reports of
extralimbic involvement are limited. We describe four cases of GAD antibody
related autoimmune encephalitis. Three of them had extralimbic involvement and
only one had limbic encephalitis.
PMID- 29349680
TI - Ultrasound evaluation of the airway in the ED: a feasibility study.
AB - BACKGROUND: Recognition of the difficult airway is a critical element of
emergency practice. Mallampati score and body mass index (BMI) are not always
predictive and they may be unavailable in critically ill patients.
Ultrasonography provides high-resolution images that are rapidly obtainable,
mobile, and non-invasive. Studies have shown correlation of ultrasound
measurements with difficult laryngoscopy; however, none have been performed in
the Emergency Department (ED) using a consistent scanning protocol. OBJECTIVES:
This study seeks to determine the feasibility of ultrasound measurements of the
upper airway performed in the ED by emergency physicians, the inter-rater
reliability of such measurements, and their relationship with Mallampati score
and BMI. METHODS: A convenience sample of volunteer ED patients and healthy
volunteers with no known airway issues, aged > 18 years, had images taken of
their airway using a standardized ultrasound scanning protocol by two EM
ultrasound fellowship trained physicians. Measurements consisted of tongue base,
tongue base-to-skin, epiglottic width and thickness, and pre-epiglottic space.
Mean and standard deviation (SD) were used to summarize measurements. Inter-rater
reliability was assessed by intraclass correlation coefficients (ICCs). Analysis
of variance with linear contrasts was used to compare measurements with
Mallampati scores and linear regression with BMI. RESULTS: Of 39 participants,
50% were female, 50% white, 42% black, with median age 32.5 years (range 19-90),
and BMI 26.0 (range 19-47). Mean +/- SD for each measurement (mm) was as follows:
tongue base (44.6 +/- 5.1), tongue base-to-skin (60.9 +/- 5.3), epiglottic width
(15.0 +/- 2.8) and thickness (2.0 +/- 0.37), and pre-epiglottic space (11.4 +/-
2.4). ICCs ranged from 0.76 to 0.88 for all measurements except epiglottis
thickness (ICC = 0.57). Tongue base and tongue base-to-skin thickness were found
to increase with increasing Mallampati score (p = .04, .01), whereas only tongue
to-skin thickness was loosely correlated with BMI (r = .38). CONCLUSIONS: A
standardized ultrasound scanning protocol demonstrates that the airway can be
measured by emergency sonologists with good inter-operator reliability in all but
epiglottic thickness. The measurements correlate with Mallampati score but not
with BMI. Future investigation might focus on ultrasound evaluation of the airway
in patients receiving airway management to determine whether ultrasound can
predict challenging or abnormal airway anatomy prior to laryngoscopy.
PMID- 29349681
TI - Erratum to: Functional Analysis of Membrane Proteins Produced by Cell-Free
Translation.
PMID- 29349682
TI - Managing Obesity in Primary Care: Breaking Down the Barriers.
AB - : Several Australian obesity management guidelines have been developed for
general practice but, to date, implementation of these guidelines has been shown
to be inadequate. In this review, we explore the barriers to obesity treatment
and propose a four-stage plan to manage individuals with obesity in general
practice using a framework of a multidisciplinary team. FUNDING: Novo Nordisk.
PMID- 29349683
TI - Plantamajoside Inhibits Lipopolysaccharide-Induced MUC5AC Expression and
Inflammation through Suppressing the PI3K/Akt and NF-kappaB Signaling Pathways in
Human Airway Epithelial Cells.
AB - It has been reported that plantamajoside (PMS), a major natural compound isolated
from Plantago asiatica, has anti-inflammatory activities. However, the effect of
PMS on respiratory inflammatory diseases has not yet been studied. The present
study aimed to evaluate the effect of PMS on lipopolysaccharide (LPS)-induced
airway inflammation and the underlying mechanism. The results showed that PMS did
not affect the cell viability of 16-HBE cells. PMS (20 and 40 MUg/ml) decreased
the expression levels of MUC5AC, IL-6, and IL-1beta, which were induced by LPS
treatment. PMS inhibited the LPS-induced phosphorylation of Akt and p65. In
addition, inhibitors of the PI3K/Akt and NF-kappaB pathways attenuated the effect
of LPS on 16-HBE cells. In conclusion, PMS inhibits LPS-induced MUC5AC expression
and inflammation through suppressing the PI3K/Akt and NF-kappaB signaling
pathways, indicating that PMS may be a potential therapy for the treatment of
respiratory inflammatory diseases.
PMID- 29349684
TI - Fcgamma Receptor Signaling in Phagocytes.
AB - Fcgamma receptors are among the best-studied phagocytic receptors. The key
features of Fcgamma receptor-mediated phagocytosis include phagocytic cup
formation by extensive actin cytoskeletal rearrangements, particle engulfment,
and the release of proinflammatory mediators such as cytokines and reactive
oxygen species. These events are elegantly regulated by the simultaneous
engagement of activating and inhibitory Fcgamma receptors and by intracellular
signaling molecules. Extensive studies in the past several years have defined the
molecular mechanisms of the phagocytic process. The purpose of this review is to
revisit some of the well-established signaling pathways as well as to summarize
the new findings in this field.
PMID- 29349686
TI - Two-year results after coronary stenting of small vessels in Japanese population
using 2.25-mm diameter sirolimus-eluting stent with bioresorbable polymer:
primary and long-term outcomes of CENTURY JSV study.
AB - : Percutaneous coronary intervention (PCI) in coronary artery disease (CAD) with
very small vessels remains challenging. The aim of this study is to evaluate the
safety and effectiveness of the 2.25-mm diameter Ultimaster sirolimus-eluting
stent in the treatment of Japanese patients with CAD due to lesions in very small
vessels. The CENTURY JSV study is a prospective, multicentre, single-arm study.
Seventy patients with lesions deemed suitable for implantation of a 2.25-mm
diameter stent were enrolled at seven hospitals in Japan. Patients underwent
clinical follow-up at 1-, 9-month, 1-, and 2-year after the PCI procedure. The
primary endpoint was the major adverse cardiac event (MACE), a composite of
cardiac death, target vessel myocardial infarction (MI), and clinically driven
target lesion revascularization (TLR) free rate at 9-month following the
procedure. The MACE-free rate was 97.1%, and the lower limit of the two-sided 95%
confidence interval (CI) was 90.1%, which exceeded the threshold of 80% set as
the performance goal. Angiographic in-stent and in-segment late loss at 9-month
were 0.22 +/- 0.31 and - 0.02 +/- 0.34 mm, respectively. Between 9 months and 2
years, two additional TLRs occurred. Stent thrombosis, bleeding and vascular
complication did not occur throughout 2 years. The 2.25-mm diameter Ultimaster(r)
bioresorbable-polymer sirolimus-eluting stent is safe and effective for treating
lesions in very small coronary arteries throughout 2 years after stent
implantation. CLINICAL TRIAL REGISTRATION: UMIN000012928.
PMID- 29349685
TI - Solute Transport in the Bone Lacunar-Canalicular System (LCS).
AB - PURPOSE OF REVIEW: Solute transport in the lacunar-canalicular system (LCS) plays
important roles in osteocyte metabolism and cell-cell signaling. This review will
summarize recent studies that establish pericellular matrix (PCM), discovered
inside the LCS, as a crucial regulator of solute transport in bone. RECENT
FINDINGS: Utilizing confocal imaging and mathematical modeling, recent studies
successfully quantified molecular diffusion and convection in the LCS as well as
the size-dependent sieving effects of the PCM, leading to the quantification of
the effective PCM fiber spacing (10 to 17 nm) in murine adult bones.
Perlecan/HSPG2, a large linear proteoglycan, was identified to be an essential
PCM component. The PCM-filled LCS is bone's chromatographic column, where
fluid/solute transport to and from the osteocytes is regulated. The chemical
composition, deposition rate, and turnover rate of the osteocyte PCM should be
further defined to better understand osteocyte physiology and bone metabolism.
PMID- 29349687
TI - Adjunct and rescue therapies for refractory hypoxemia: prone position, inhaled
nitric oxide, high frequency oscillation, extra corporeal life support.
PMID- 29349688
TI - Immunoglobulins and sepsis.
PMID- 29349689
TI - Suspended in time and space.
PMID- 29349690
TI - Transthoracic cardiac ultrasound in prone position: a technique variation
description.
PMID- 29349691
TI - Subtle trajectories.
PMID- 29349692
TI - Ascites Due to Constrictive Pericardial Disease Not Appreciated on
Echocardiogram: A Report of Three Cases.
PMID- 29349693
TI - Anti-Tumor Necrosis Factor-alpha-Induced Dermatological Complications in a Large
Cohort of Inflammatory Bowel Disease Patients.
AB - BACKGROUND/AIMS: The broader use of anti-tumor necrosis factor (TNF) agents in
inflammatory bowel disease (IBD) has been associated with a high rate of adverse
reactions. Dermatological complications are among the most common adverse events.
We assessed the incidence, risk factors, management, and outcome of anti-TNF
induced dermatological complications in a large cohort of IBD patients. METHODS:
This was an observational retrospective study at a single tertiary referral
center. All consecutive adult IBD patients treated with anti-TNF agents between
2005 and 2015 were identified. Patients who developed at least one dermatological
complication while on anti-TNF therapy were included. RESULTS: From the 732
patients treated with anti-TNF agents, 211 (29%) developed at least one
dermatological complication: 52% women (mean age of 42 +/- 13 years), 85% with
Crohn's disease, 67% were under infliximab. Median follow-up time under anti-TNF
therapy was 53 (27-77) months. Dermatological complications recorded were:
infections (13.5%), psoriasiform lesions (5.3%), injection/infusion reactions
(3.8%), skin cancer (0.5%), and miscellaneous (5.6%). Overall, female gender (OR
= 1.658, p = 0.029), smoking (OR = 2.021, p = 0.003), and treatment with an
infliximab dose of 10 mg/kg (OR = 2.012, p = 0.007) were independent risk factors
for dermatological complications in multivariable analysis. Female gender (OR =
3.63, p = 0.017), smoking (OR = 2.846, p = 0.041), and treatment with adalimumab
(OR = 8.894, p < 0.001) were independently associated with development of
psoriasiform lesions. Three (3%) patients with infectious complications and 12
(31%) patients with psoriasiform lesions discontinued anti-TNF therapy
definitively. CONCLUSIONS: Dermatological manifestations occurred in almost one
third of our population. Infections were the most common complication, but anti
TNF-induced psoriasiform lesions were the most common cause for anti-TNF therapy
definitive discontinuation.
PMID- 29349694
TI - Endoscopic Ultrasound-Guided Rendezvous Technique for Failed Biliary Cannulation
in Benign and Resectable Malignant Biliary Disorders.
AB - BACKGROUND: Endoscopic ultrasound-guided rendezvous technique (EUS-RV) has
emerged as an effective salvage method for unsuccessful biliary cannulation.
However, its application for benign and resectable malignant biliary disorders
has not been fully evaluated. AIMS: To assess the efficacy and safety of EUS-RV
for benign and resectable malignant biliary disorders. METHODS: This was a
multicenter prospective study from 12 Japanese referral centers. Patients who
underwent EUS-RV after failed biliary cannulation for biliary disorder were
candidates for this study. Inclusion criteria were unsuccessful biliary
cannulation for therapeutic endoscopic retrograde cholangiopancreatography with
benign and potentially resectable malignant biliary obstruction. Exclusion
criteria included unresectable malignant biliary obstruction, inaccessible
papillae due to surgically altered upper gastrointestinal anatomy or duodenal
stricture, and previous sphincterotomy and/or biliary stent placement. The
primary outcome was the technical success rate of biliary cannulation; procedure
time, adverse events, and clinical outcomes were secondary outcomes. RESULTS:
Twenty patients were prospectively enrolled. The overall technical success rate
and median procedure time were 85% and 33 min, respectively. Guidewire
manipulation using a 4-Fr tapered tip catheter contributed to the success in
advancing the guidewire into the duodenum. Adverse events were identified in 15%
patients, including 2 with biliary peritonitis and 1 mild pancreatitis. EUS-RV
did not affect surgical maneuvers or complications associated with surgery, or
postoperative course. CONCLUSIONS: EUS-RV may be a safe and feasible salvage
method for unsuccessful biliary cannulation for benign or resectable malignant
biliary disorders. Use of a 4-Fr tapered tip catheter may improve the overall EUS
RV success rate.
PMID- 29349695
TI - Efficacy of Atopy Patch Testing in Directed Dietary Therapy of Eosinophilic
Esophagitis: A Pilot Study.
AB - BACKGROUND: Atopy patch testing (APT) has shown potential for predicting dietary
food triggers in studies of children and adolescents with eosinophilic
esophagitis (EoE). AIMS: To assess the efficacy of APT in adults with EoE.
METHODS: We conducted a prospective open-label pilot study of patients >= 18
years old with diagnosis of EoE at Mayo Clinic in Rochester, Minnesota, from
November 2014 to January 2016. All patients underwent patch testing using intact
food products, followed by a six food elimination diet and stepwise food
reintroduction. Response to elimination diet was assessed with serial endoscopy
with biopsies as well as clinical symptoms. APT results were directly compared to
elimination diet results for assessment of efficacy. Correlation between clinical
symptoms, endoscopic score, and histology was also qualitatively evaluated.
RESULTS: Fifty percent of the patients had a positive APT, while only 16% had an
APT result confirmed histologically during food reintroduction. Sensitivity of
APT was calculated to be 5.9%, with specificity of 92.0%. Furthermore, we found
significant qualitative inter-patient heterogeneity in the correlation between
clinical symptoms, EREFS score, and histology. CONCLUSIONS: APT does not reliably
predict food triggers identified by food elimination diet in adult patients with
EoE. As a result, APT does not have a clear role in the evaluation of patients
with EoE.
PMID- 29349696
TI - Assessing priming for prosodic representations: Speaking rate, intonational
phrase boundaries, and pitch accenting.
AB - Recent work in the literature on prosody presents a puzzle: Some aspects of
prosody can be primed in production (e.g., speech rate), but others cannot (e.g.,
intonational phrase boundaries, or IPBs). In three experiments we aimed to
replicate these effects and identify the source of this dissociation. In
Experiment 1 we investigated how speaking rate and the presence of an
intonational boundary in a prime sentence presented auditorily affect the
production of these aspects of prosody in a target sentence presented visually.
Analyses of the targets revealed that participants' speaking rates, but not their
production of boundaries, were affected by the priming manipulation. Experiment 2
verified whether speakers are more sensitive to IPBs when the boundaries provide
disambiguating information, and in this different context replicated Experiment 1
in showing no IPB priming. Experiment 3 tested whether speakers are sensitive to
another aspect of prosody-pitch accenting-in a similar paradigm. Again, we found
no evidence that this manipulation affected pitch accenting in target sentences.
These findings are consistent with earlier research and suggest that aspects of
prosody that are paralinguistic (like speaking rate) may be more amenable to
priming than are linguistic aspects of prosody (such as phrase boundaries and
pitch accenting).
PMID- 29349697
TI - To share or not to share? Expected pros and cons of data sharing in radiological
research.
AB - : The aims of this paper are to illustrate the trend towards data sharing, i.e.
the regulated availability of the original patient-level data obtained during a
study, and to discuss the expected advantages (pros) and disadvantages (cons) of
data sharing in radiological research. Expected pros include the potential for
verification of original results with alternative or supplementary analyses
(including estimation of reproducibility), advancement of knowledge by providing
new results by testing new hypotheses (not explored by the original authors) on
pre-existing databases, larger scale analyses based on individual-patient data,
enhanced multidisciplinary cooperation, reduced publication of false studies,
improved clinical practice, and reduced cost and time for clinical research.
Expected cons are outlined as the risk that the original authors could not
exploit the entire potential of the data they obtained, possible failures in
patients' privacy protection, technical barriers such as the lack of standard
formats, and possible data misinterpretation. Finally, open issues regarding data
ownership, the role of individual patients, advocacy groups and funding
institutions in decision making about sharing of data and images are discussed.
KEY POINTS: * Regulated availability of patient-level data of published clinical
studies (data-sharing) is expected. * Expected benefits include
verification/advancement of knowledge, reduced cost/time of research, clinical
improvement. * Potential drawbacks include faults in patients' identity
protection and data misinterpretation.
PMID- 29349698
TI - Third generation dual-source CT enables accurate diagnosis of coronary restenosis
in all size stents with low radiation dose and preserved image quality.
AB - OBJECTIVES: To investigate the diagnostic performance of low dose stent imaging
in patients with large (>= 3 mm) and small (< 3 mm) calibre stents by third
generation dual-source CT. METHODS: Symptomatic patients suspected of having in
stent restenosis (ISR) were prospectively enrolled. Coronary computed tomography
angiography (CCTA) and invasive coronary angiography (ICA) were performed within
1 month for correlation. Binary ISR was defined as an in-stent neointimal
proliferation with diameter stenosis >= 50%. The radiation dose and image quality
of CCTA were also assessed. RESULTS: Sixty-nine patients with 140 stents were
ultimately included for analysis. The mean total radiation dose of CCTA was 1.3
+/- 0.72 mSv in all patients and 0.95 +/- 0.17 mSv in patients with high pitch
acquisition. The overall diagnostic accuracy of CCTA stent imaging of patient
based, lesion-based and stent-based analysis was 95.7%, 94.1% and 94.3%,
respectively. Further, the diagnostic accuracy of CCTA in the small calibre stent
group (diameter < 3 mm) was slightly lower than that of the large calibre stent
group (diameter >= 3 mm) (88.5% versus 98.7%, p = 0.01). CONCLUSIONS: Third
generation dual-source CT enables accurate diagnosis of coronary ISR of both
large and small calibre stents. Low radiation dose could be achieved with
preserved image quality. KEY POINTS: * Third-generation DSCT enables accurate
diagnosis of coronary ISR of all size stents. * Low radiation dose could be
achieved with preserved image quality. * The diagnostic accuracy of CCTA of small
calibre stents was 88.5%.
PMID- 29349699
TI - To evaluate the feasibility of magnetic resonance imaging in predicting unusual
site ectopic pregnancy: a retrospective cohort study.
AB - OBJECTIVE: To evaluate the accuracy of pelvic MRI in the diagnosis of unusual
ectopic pregnancy (EP), when ultrasound (US) examination is inconclusive.
METHODS: We retrospectively reviewed the medical records of 150 patients with
suspected EP. Clinical, US and MRI features of 15 unusual EPs were analysed. Two
radiologists independently reviewed each case resolving by consensus any
diagnostic discrepancy. Interobserver agreement was assessed using the Cohen
kappa test. RESULTS: MRI displayed a gestational sac-like structure surrounded by
a thick wall in all cases. The thick wall displayed hyperintensity in 41 %,
isointensity in 35 % and hypointensity in 24 % of cases on T1-weighted images.
Diffusion- and fat saturation T1-weighted images were the most accurate
sequences, as they enabled identification of 15/15 and 14/15 patients,
respectively. Although US was false negative in detecting cervical and uterine
infiltration underlying the caesarean scar, MRI was able to identify the
invasion. Interobserver agreement was very good for all sequences (kappa=0.892
1.0). CONCLUSIONS: MRI plays an important role in the early diagnosis of unusual
EP. It should be considered after negative US findings, providing accurate
evaluation of the site and the possible infiltration of these lesions, which help
in the management of these patients. KEY POINTS: * MRI is being increasingly used
as a problem-solving modality in ectopic pregnancy. * MRI plays an important role
in early diagnosis of unusual ectopic pregnancy. * Knowledge of MRI features in
EP is essential to determinate appropriate management.
PMID- 29349700
TI - Adrenergic and metabolic effects of electrical weapons: review and meta-analysis
of human data.
AB - INTRODUCTION: Electronic control with the CEW (conducted electrical weapon) has
gained widespread acceptance as the preferred force option due to its significant
injury reduction. However, a CEW application does stress the human body. In the
case of the CEW, the human body response is similar to the challenge of physical
exercise combined with emotional stress over a very short time interval. There
has been concern whether the tension of the skeletal-muscle system together with
the emotional stress of being exposed to the effects of a CEW, can lead to severe
metabolic dysfunction. METHODS: A systematic and careful search of the MedLine
database was performed to find publications describing pathophysiological effects
of CEWs. Additional publications were collected through a manual search of
reference lists in retrieved articles. After preliminary exclusions, we carefully
reviewed the remaining publications and found 24 papers reporting prospective
human clinical research data on adrenergic, ventilation, or metabolic effects.
Where there were multiple studies on the same endpoints, we performed meta
analyses. RESULTS: A CEW exposure provides a clinically insignificant increase in
heart rate (7.5 BPM) and a drop in both systolic and diastolic blood pressure.
Alpha-amylase goes down but cortisol levels increase-both epinephrine and
norepinephrine levels are increased by levels similar to mild exercise. A CEW
exposure increases ventilation but does not appear to interfere with gas
exchange. Lactate is increased slightly while the pH is decreased slightly with
changes equivalent to mild exercise. The lactate and pH changes appear quickly
and do not appear to be affected by increasing the exposure duration from 5 to 30
s. CONCLUSIONS: Thorough review and meta-analyses show that electrical weapon
exposures have mixed and mild adrenergic effects. Ventilation is increased and
there are metabolic changes similar to mild exercise.
PMID- 29349701
TI - Chicken Egg Yolk Antibodies Specific for the gamma Chain of Human Hemoglobin for
Diagnosis of Thalassemia.
AB - Immunoglobulin Y (IgY) technology was used to generate anti-hemoglobin Bart's (Hb
Bart's) IgY antibodies (Abs) for development into an enzyme-linked immunosorbent
assay (ELISA) test for thalassemia diagnosis. Hb Bart's purified from the
hemolysate of a patient with Hb Bart's hydrops fetalis (homozygous alpha
thalassemia) was used to immunize a chicken via the pectoralis muscle. After
water dilution and sodium sulfate precipitation, 40 to 70 mg of IgY could be
extracted from an egg. IgY, first detected in sera 2 weeks after immunization,
reached the highest titer at week 4, and the titer remained stable for at least 2
weeks before declining. The pattern of Ab response in the yolk was the same as in
the serum but was somewhat delayed. The IgY Abs produced reacted with gamma
globin, Hb Bart's, Hb F, normal cord hemolysate (Hbs F plus A), and Hb Bart's
hydrops fetalis (Hbs Bart's plus Portland) and to a lesser degree with beta
globin, Hb A, Hb A2, and adult hemolysate (Hbs A plus A2), but the Abs did not
react with alpha globin. Immunoaffinity purification with Hb A coupled to
Sepharose was used to isolate an unbound IgY that reacted with Hb F, Hb Bart's,
and gamma globin, and this IgY was used to develop an ELISA test for thalassemia
diagnosis. The results of direct ELISA analyses of 336 hemolysate samples from
individuals with various known thalassemia genotypes and phenotypes and from
healthy individuals confirmed the specificity of the polyclonal Abs for Hbs
containing Hb F and Hb Bart's. This specificity, which was due to the Abs' strong
reactivity in cases of pathologic thalassemic diseases and weak reactivity in
cases of nonpathologic thalassemic diseases, depended on the levels of Hb Bart's
and Hb F.
PMID- 29349702
TI - Transcription Factors: Normal and Malignant Development of Blood Cells.
PMID- 29349704
TI - Peroxisome Proliferator-Activated Receptor gamma and Retinoic Acid Receptor
Synergistically Up-Regulate the Tumor Suppressor PTEN in Human Promyeloid
Leukemia Cells.
AB - Peroxisome proliferator-activated receptor gamma (PPARgamma) and retinoic acid
receptors (RARs) have been a focus in chemotherapy for human cancers. The tumor
suppressor PTEN plays a pivotal role in the growth of human cancer cells. We
investigated whether costimulation of PPARgamma and RAR could synergistically up
regulate PTEN in human leukemia cells and consequently potentiate the inhibition
of growth and cell cycle progression of these cells. We found that overexpression
of PTEN with the adenoviral vector Ad/PTEN caused growth arrest at the G1 phase
of the cell cycle of HL-60 cells. HL-60 cells treated with either a PPARgamma
ligand (ciglitazone) or a RAR ligand(all-trans retinoic acid [ATRA]) up-regulated
PTEN in HL-60 cells. The 2 compounds in combination showed synergistic effects on
PTEN expression at the protein and messenger RNA levels. Moreover, the
combination of ciglitazone and ATRA synergistically reduced cell growth rates and
cell cycle arrest at the G1 phase. Our results suggest that, PPARgamma and RAR
play an important role in controlling the growth of leukemia cells via the up
regulation of PTEN.
PMID- 29349703
TI - Matrix Stiffness: the Conductor of Organ Fibrosis.
AB - PURPOSE OF REVIEW: Organ fibrosis is a lethal component of scleroderma. The
hallmark of scleroderma fibrosis is extensive extracellular matrix (ECM)
deposition by activated myofibroblasts, specialized hyper-contractile cells that
promote ECM remodeling and matrix stiffening. The purpose of this review is to
discuss novel mechanistic insight into myofibroblast activation in scleroderma.
RECENT FINDINGS: Matrix stiffness, traditionally viewed as an end point of organ
fibrosis, is now recognized as a critical regulator of tissue fibrogenesis that
hijacks the normal physiologic wound-healing program to promote organ fibrosis.
Here, we discuss how matrix stiffness orchestrates fibrosis by controlling three
fundamental pro-fibrotic mechanisms: (a) mechanoactivation of myofibroblasts, (b)
integrin-mediated latent transforming growth factor beta 1 (TGF-beta1)
activation, and (c) activation of non-canonical TGF-beta1 signaling pathways. We
also summarize novel therapeutic targets for anti-fibrotic therapy based on the
mechanobiology of scleroderma. Future research on mechanobiology of scleroderma
may lead to important clinical applications such as improved diagnosis and
treatment of patients with scleroderma and other fibrotic-related diseases.
PMID- 29349705
TI - Stool cultures at the ICU: get rid of it!
AB - BACKGROUND: Stool cultures for Campylobacter, Salmonella and Shigella and/or
Yersinia spp. are frequently ordered in critically ill patients with diarrhea.
The aim of this study is to analyze the diagnostic yield in a large cohort of
critically ill patients. Therefore, we performed a cohort study at the Department
of Intensive Care Medicine of a University Hospital (11 ICUs). RESULTS: From all
patients who were admitted to the ICU between 2010 and 2015, stool cultures were
taken from 2.189/36.477 (6%) patients due to diarrhea. Results of all stool
cultures tested for Campylobacter, Salmonella and Shigella and/or Yersinia spp.
were analyzed. Overall, 5.747 tests were performed; only six were positive
(0.1%). In four of these, Campylobacter spp. were detected; diarrhea started
within 48 h after ICU admission. Two patients with Salmonella spp. detection were
chronic shedders. On the contrary, testing for Clostridium difficile via GDH- and
toxin A/B-EIA yielded positive results in 179/2209 (8.1%) tests and revealed
144/2.189 (6.6%) patients with clinically relevant C. difficile infection.
CONCLUSIONS: Stool testing for enteric pathogens other than C. difficile should
be avoided in ICU patients and is only reasonable when diarrhea commenced less
than 48 h after hospital admission.
PMID- 29349707
TI - Piperazine clubbed with 2-azetidinone derivatives suppresses proliferation,
migration and induces apoptosis in human cervical cancer HeLa cells through
oxidative stress mediated intrinsic mitochondrial pathway.
AB - Piperazine scaffolds or 2-azetidinone pharmacophores have been reported to show
anti-cancer activities and apoptosis induction in different types of cancer
cells. However, the mechanistic studies involve in induction of apoptosis
addressing these two moieties for human cervical cancer cells remain uncertain.
The present study emphasizes on the anti-proliferating properties and mechanism
involved in induction of apoptosis for these structurally related azoles
derivatives in HeLa cancer cells. 1-Phenylpiperazine clubbed with 2-azetidione
derivatives (5a-5h) were synthesized, characterized using various spectroscopic
techniques and evaluated for their in-vitro anti-proliferative activities and
induction of apoptosis. Further, we also evaluated oxidative stress generated by
these synthetic derivatives (5a-5h). Cell viability studies revealed that among
all, the compound N-(3-chloro-2-(3-nitrophenyl)-4-oxoazetidin-1-yl)-2-(4
phenylpiperazin-1-yl) acetamide 5e remarkably inhibited the growth of HeLa cells
in a concentration dependent manner having IC50 value of 29.44 +/- 1.46 ug/ml.
Morphological changes, colonies suppression and inhibition of migration clearly
showed the antineoplasicity in HeLa cells treated with 5e. Simultaneously,
phosphatidylserine externalization, DNA fragmentation and cell-cycle arrest
showed ongoing apoptosis in the HeLa cancer cells induced by compound 5e in
concentration dependent manner. Additionally, generation of intracellular ROS
along with the decrease in mitochondrial membrane potential supported that
compound 5e caused oxidative stress resulting in apoptosis through mitochondria
mediated pathway. Elevation in the level of cytochrome c and upregulation in
expression of caspase-3 clearly indicated the involvement of the intrinsic
pathway of programmed cell death. In brief; compound 5e could serve as a
promising lead for the development of an effective antitumor agent.
PMID- 29349706
TI - Effect of the combination of mephedrone plus ethanol on serotonin and dopamine
release in the nucleus accumbens and medial prefrontal cortex of awake rats.
AB - Cathinones, such as mephedrone (Meph), are often co-abused with alcoholic drinks.
In the present study, we investigated the combined effects of Meph plus ethanol
(EtOH) on neurotransmitter release in the nucleus accumbens (NAc) and the medial
prefrontal cortex (mPFC). A guide canula was stereotaxically implanted into
either the NAc or the mPFC of male Sprague-Dawley rats. Seven days after surgery,
a microdialysis probe was inserted and rats were administered saline, EtOH (1
g/kg, i.p.), Meph (25 mg/kg, s.c.), or their combination, and dialysates were
collected. Serotonin (5-HT), dopamine (DA), and their metabolites (5-HIAA, DOPAC
and HVA) were determined through high-pressure liquid chromatography coupled to
mass spectrometry. 5-HT and DA peaked 40 min after Meph administration (with or
without EtOH co-treatment) in both areas. EtOH combined with Meph increased the 5
HT release compared with the rats receiving Meph alone (85% in NAc, 65% in mPFC),
although the overall change in the area under the curve only reached statistical
significance in the NAc. In mPFC, the increased release of 5-HT lasted longer in
the combination than that in the Meph group. Moreover, EtOH potentiated the
psychostimulant effect of Meph measured as a locomotor activity. Given that both
5-HT and DA are also related with reward and impulsivity, the observed effects
point to an increased risk of abuse liability when combining Meph with EtOH
compared with consuming these drugs alone.
PMID- 29349708
TI - Cost-Effectiveness of Empagliflozin for the Treatment of Patients with Type 2
Diabetes Mellitus at Increased Cardiovascular Risk in Greece.
AB - BACKGROUND AND OBJECTIVE: Type 2 diabetes mellitus (T2DM) is frequently
associated with co-morbidities that exacerbate cardiovascular (CV) risk. CV
disease is the leading cause of death in people with diabetes across the world
and accounts for approximately half the deaths in the T2DM population. Hence, the
objective of present study was to evaluate the cost-effectiveness of
empagliflozin, in addition to standard of care (SoC), for the treatment of adult
patients with T2DM and high CV risk in Greece. METHODS: A health economic model
was used to project clinical and economic outcomes of patients receiving
empagliflozin plus SoC compared with those receiving SoC alone over a lifetime
horizon. CV and renal event rates were derived from patient level data from the
EMPA-REG-OUTCOME(r) trial by fitting time-dependent parametric survival
functions. 5000 individual patient profiles randomly sampled from the trial were
simulated using a time-to-event approach. Model extrapolated outcomes included
life years (LYs), quality-adjusted life years (QALYs), costs, and incremental
cost-effectiveness ratio (ICER). Following a Greek third-party payer perspective,
only direct medical costs related to drug acquisition as well as fatal and non
fatal diabetes-related complications were considered (?2016). Cost units and
utility data were extracted from the literature and publicly available official
sources. Sensitivity analyses explored the impact of changes in input data.
RESULTS: Over a patient's lifetime, empagliflozin was predicted to result in
longer mean survival (14.01 LY vs. 11.87 LY with SoC) and reduced rate of
clinical events accumulating 7.75 QALYs versus 6.83 QALYs on SoC alone at
additional costs of ?4235. The generated ICER of empagliflozin was ?4633 per QALY
gained. One-way sensitivity analysis confirmed empagliflozin's cost-effective
profile. At the defined willingness-to-pay threshold of ?34,000 per QALY gained,
probabilistic sensitivity analysis showed that empagliflozin was estimated to
have a 100% probability of being cost-effective relative to SoC. CONCLUSIONS:
Empagliflozin added to SoC was estimated to be a highly cost-effective treatment
option for the treatment of T2DM in adults with increased CV disease risk in
Greece.
PMID- 29349709
TI - The host response in critically ill sepsis patients on statin therapy: a
prospective observational study.
AB - BACKGROUND: Statins can exert pleiotropic anti-inflammatory, vascular protective
and anticoagulant effects, which in theory could improve the dysregulated host
response during sepsis. We aimed to determine the association between prior
statin use and host response characteristics in critically ill patients with
sepsis. METHODS: We performed a prospective observational study in 1060 patients
admitted with sepsis to the mixed intensive care units (ICUs) of two hospitals in
the Netherlands between January 2011 and July 2013. Of these, 351 patients (33%)
were on statin therapy before admission. The host response was evaluated by
measuring 23 biomarkers providing insight into key pathways implicated in sepsis
pathogenesis and by analyzing whole-blood leukocyte transcriptomes in samples
obtained within 24 h after ICU admission. To account for indication bias, a
propensity score-matched cohort was created (N = 194 in both groups for protein
biomarkers and N = 95 in both groups for gene expression analysis). RESULTS:
Prior statin use was not associated with an altered mortality up to 90 days after
admission (38.0 vs. 39.7% in the non-statin users in the propensity-matched
analysis). Statin use did not modify systemic inflammatory responses, activation
of the vascular endothelium or the coagulation system. The blood leukocyte
genomic response, characterized by over-expression of genes involved in
inflammatory and innate immune signaling pathways as well as under-expression of
genes associated to T cell function, was not different between patients with and
without prior statin use. CONCLUSIONS: Statin therapy is not associated with a
modified host response in sepsis patients on admission to the ICU.
PMID- 29349710
TI - Digital image analysis of Ki67 proliferation index in breast cancer using virtual
dual staining on whole tissue sections: clinical validation and inter-platform
agreement.
AB - PURPOSE: The Ki67 proliferation index is a prognostic and predictive marker in
breast cancer. Manual scoring is prone to inter- and intra-observer variability.
The aims of this study were to clinically validate digital image analysis (DIA)
of Ki67 using virtual dual staining (VDS) on whole tissue sections and to assess
inter-platform agreement between two independent DIA platforms. METHODS: Serial
whole tissue sections of 154 consecutive invasive breast carcinomas were stained
for Ki67 and cytokeratin 8/18 with immunohistochemistry in a clinical setting.
Ki67 proliferation index was determined using two independent DIA platforms,
implementing VDS to identify tumor tissue. Manual Ki67 score was determined using
a standardized manual counting protocol. Inter-observer agreement between manual
and DIA scores and inter-platform agreement between both DIA platforms were
determined and calculated using Spearman's correlation coefficients. Correlations
and agreement were assessed with scatterplots and Bland-Altman plots. RESULTS:
Spearman's correlation coefficients were 0.94 (p < 0.001) for inter-observer
agreement between manual counting and platform A, 0.93 (p < 0.001) between manual
counting and platform B, and 0.96 (p < 0.001) for inter-platform agreement.
Scatterplots and Bland-Altman plots revealed no skewness within specific data
ranges. In the few cases with >= 10% difference between manual counting and DIA,
results by both platforms were similar. CONCLUSIONS: DIA using VDS is an accurate
method to determine the Ki67 proliferation index in breast cancer, as an
alternative to manual scoring of whole sections in clinical practice. Inter
platform agreement between two different DIA platforms was excellent, suggesting
vendor-independent clinical implementability.
PMID- 29349711
TI - Impact of an embedded genetic counselor on breast cancer treatment.
AB - BACKGROUND: We predicted that embedding a genetic counselor within our breast
practice would improve identification of high-risk individuals, timeliness of
care, and appropriateness of surgical decision making. The aim of this study is
to compare cancer care between 2012 and 2014, prior to embedding a genetic
counselor in the breast center and following the intervention, respectively.
METHODS: A retrospective review of patients diagnosed with breast cancer in 2012
(n = 471) and 2014 (n = 440) was performed to assess patterns of medical genetics
referral, compliance with referral, genetic testing findings, and impact on
treatment. RESULTS: Between 2012 and 2014, patients were 49% more likely to be
referred to genetics, 66% more likely to follow through with their genetic
counseling appointment, experienced a 73% reduction in wait times to genetic
counseling visits and 69% more likely to have genetic testing results prior to
surgery. Notably, while the number of genetic mutations identified was in the
expected range over both time periods (9% of those tested in 2012 vs. 6.6% of
those tested in 2014), there was a 31% reduction in time to treatment in 2014 vs.
2012. CONCLUSION: Awareness of germline genetic mutations is critical in surgical
decision making for newly diagnosed breast cancer patients. Having an experienced
genetics specialist on site in a busy surgical breast clinic allows for timely
access to genetic counseling and testing, and may have influenced time to
treatment in our institution.
PMID- 29349712
TI - Highly favorable physiological responses to concurrent resistance and high
intensity interval training during chemotherapy: the OptiTrain breast cancer
trial.
AB - BACKGROUND: Advanced therapeutic strategies are often accompanied by significant
adverse effects, which warrant equally progressive countermeasures. Physical
exercise has proven an effective intervention to improve physical function and
reduce fatigue in patients undergoing chemotherapy. Effects of high-intensity
interval training (HIIT) in this population are not well established although
HIIT has proven effective in other clinical populations. The aim of the OptiTrain
trial was to examine the effects of concurrent resistance and high-intensity
interval training (RT-HIIT) or concurrent moderate-intensity aerobic and high
intensity interval training (AT-HIIT), to usual care (UC) on pain sensitivity and
physiological outcomes in patients with breast cancer during chemotherapy.
METHODS: Two hundred and forty women were randomized to 16 weeks of RT-HIIT, AT
HIIT, or UC. OUTCOMES: cardiorespiratory fitness, muscle strength, body mass,
hemoglobin levels, and pressure-pain threshold. RESULTS: Pre- to post
intervention, RT-HIIT (ES = 0.41) and AT-HIIT (ES = 0.42) prevented the reduced
cardiorespiratory fitness found with UC. Handgrip strength (surgery side: RT-HIIT
vs. UC: ES = 0.41, RT-HIIT vs. AT-HIIT: ES = 0.28; non-surgery side: RT-HIIT vs.
UC: ES = 0.35, RT-HIIT vs. AT-HIIT: ES = 0.22) and lower-limb muscle strength (RT
HIIT vs. UC: ES = 0.66, RT-HIIT vs. AT-HIIT: ES = 0.23) were significantly
improved in the RT-HIIT. Increases in body mass were smaller in RT-HIIT (ES = -
0.16) and AT-HIIT (ES = - 0.16) versus UC. RT-HIIT reported higher pressure-pain
thresholds than UC (trapezius: ES = 0.46, gluteus: ES = 0.53) and AT-HIIT
(trapezius: ES = 0.30). CONCLUSION: Sixteen weeks of RT-HIIT significantly
improved muscle strength and reduced pain sensitivity. Both exercise programs
were well tolerated and were equally efficient in preventing increases in body
mass and in preventing declines in cardiorespiratory fitness. These results
highlight the importance of implementing a combination of resistance and high
intensity interval training during chemotherapy for women with breast cancer.
PMID- 29349713
TI - Patient-reported outcomes of catheter-based accelerated partial breast
brachytherapy and whole breast irradiation, a single institution experience.
AB - PURPOSE: Accelerated partial breast irradiation (APBI) and whole breast
irradiation (WBI) are treatment options for early-stage breast cancer. The
purpose of this study was to compare patient-reported-outcomes (PRO) between
patients receiving multi-channel intra-cavitary brachytherapy APBI or WBI.
METHODS: Between 2012 and 2015, 131 patients with ductal carcinoma in situ (DCIS)
or early stage invasive breast cancer were treated with adjuvant APBI (64) or WBI
(67) and participated in a PRO questionnaire. The linear analog scale assessment
(LASA), harvard breast cosmesis scale (HBCS), PRO-common terminology criteria for
adverse events- PRO (PRO-CTCAE), and breast cancer treatment outcome scale
(BCTOS) were used to assess quality of life (QoL), pain, fatigue, aesthetic and
functional status, and breast cosmesis. Comparisons of PROs were performed using
t-tests, Wilcoxon rank-sum, Chi square, Fisher exact test, and regression
methods. RESULTS: Median follow-up from completion of radiotherapy and
questionnaire completion was 13.3 months. There was no significant difference in
QoL, pain, or fatigue severity, as assessed by the LASA, between treatment groups
(p > 0.05). No factors were found to be predictive of overall QoL on regression
analysis. BCTOS health-related QoL scores were similar between treatment groups
(p = 0.52).The majority of APBI and WBI patients reported excellent/good breast
cosmesis, 88.5% versus 93.7% (p = 0.37). Skin color change (p = 0.011) and breast
elevation (p = 0.01) relative to baseline were more common in the group receiving
WBI. CONCLUSIONS: APBI and WBI were both associated with favorable patient
reported outcomes in early follow-up. APBI resulted in a lesser degree of patient
reported skin color change and breast elevation relative to baseline.
PMID- 29349714
TI - DBDA as a Novel Matrix for the Analyses of Small Molecules and Quantification of
Fatty Acids by Negative Ion MALDI-TOF MS.
AB - Matrix interference ions in low mass range has always been a concern when using
matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
(MALDI-TOF MS) to analyze small molecules (<500 Da). In this work, a novel
matrix, N1,N4-dibenzylidenebenzene-1,4-diamine (DBDA) was synthesized for the
analyses of small molecules by negative ion MALDI-TOF MS. Notably, only neat ions
([M-H]-) of fatty acids without matrix interference appeared in the mass spectra
and the limit of detection (LOD) reached 0.3 fmol. DBDA also has great
performance towards other small molecules such as amino acids, peptides, and
nucleotide. Furthermore, with this novel matrix, the free fatty acids in serum
were quantitatively analyzed based on the correlation curves with correlation
coefficient of 0.99. In addition, UV-Vis experiments and molecular orbital
calculations were performed to explore mechanism about DBDA used as matrix in the
negative ion mode. The present work shows that the DBDA matrix is a highly
sensitive matrix with few interference ions for analysis of small molecules.
Meanwhile, DBDA is able to precisely quantify the fatty acids in real biological
samples. Graphical Abstract ?.
PMID- 29349715
TI - "Sex Is a sin": Afro-Caribbean Parent and Teen Perspectives on Sex Conversations.
AB - This study characterized (a) mothers' childhood and teenage experiences with sex
conversations and (b) families' perceptions of current parent-child sex
conversations within two underserved Afro-Caribbean communities in the U.S.
Fourteen dyads comprised of Haitian and Jamaican mothers and teens (aged 14-18)
living in Miami, Florida, completed semi-structured interviews sharing their
experiences with sex conversations. Researchers analyzed data using thematic
content analysis. Mothers' mean age was 41.85 years, (SD = 5.50) and teens' mean
age was 16.35 years, (SD = 1.31). Most mothers reported forbidden or little
childhood experiences with parent-child sex conversations. They affected their
sexual attitudes, behaviors, and ability to discuss sex with their children.
Although some mothers benefited from educational and skill development others
shared fear-based messages with their children that some teens believed adversely
affected the mother-child relationship quality. Culturally appropriate, skill
based approaches are necessary to improve families' communication self-efficacy
for healthy sex conversations to occur in Afro-Caribbean families.
PMID- 29349716
TI - Detection of bovine carriers of Leptospira by serological, bacteriological, and
molecular tools.
AB - Bovine leptospirosis is an important infectious disease that causes reproductive
problems and economic risks, particularly in the tropics. The present study aimed
to determine the extent of Leptospira infection among bovines on a slaughterhouse
from Rio de Janeiro, Brazil via serological, bacteriological, and molecular
tests. Two hundred eight bovines were examined in total, and we obtained 208
blood samples for serology, 198 urine samples collected via direct bladder
puncture for polymerase chain reaction (PCR) and culture, 208 kidney samples (one
from each animal) for PCR and culture, and 92 vaginal fluid samples from sterile
swabs for PCR and culture. Serology demonstrated that 77/208 (37%) of the animals
presented anti-Leptospira antibodies. Serogroup Sejroe was by far the most
common. One hundrd thirty-three animals (63.9%) were PCR positive in at least one
of the tested samples and were considered as Leptospira carriers. Furthermore,
ten isolates were obtained by pure culture, all of them from urine samples.
Bovine leptospirosis is widely prevalent, and the occurrence of renal carriers
was unexpectedly much higher than generally reported.
PMID- 29349717
TI - Analysis of Candidate Genes at the IBGC1 Locus Associated with Idiopathic Basal
Ganglia Calcification ("Fahr" Disease').
AB - Basal ganglia calcification (striatopallidodentate calcifications) can be caused
by several systemic and neurological disorders. Familial Idiopathic Basal Ganglia
Calcification (IBGC, "Fahr" disease'), is characterized by basal ganglia and
extrabasal ganglia calcifications, parkinsonism and neuropsychiatric symptoms.
Because of an increased use of neuroimaging procedures, calcifications of the
basal ganglia are visualized more often and precociously. In 1999, a major
American family with IBGC was linked to a locus on chromosome 14q (IBGC1).
Another small kindred, from Spain, has also been reported as possibly linked to
this locus. Here we report the main findings of the first 30 candidate genes
sequenced at the IBGC1 locus during the process of searching for a mutation
responsible for familial IBGC. During the sequencing process, we identified a
heterozygous nonsynonymous single nucleotide polymorphism (exon 20 of the MGEA6/c
TAGE gene) shared by the affected and not present in the controls. This SNP was
randomly screened in the general population (348 chromosomes) in a minor allele
frequency to 0.0058 (two heterozygous among 174 subjects). Another variation in
this gene, in the exon 9, was found in the Spanish family. However, this
variation was extremely common in the general population. Functional and
population studies are necessary to fully access the implications of the MGEA6
gene in familial IBGC, and a complete sequencing of the IBGC1 locus will be
necessary to define a gene responsible for familial IBGC.
PMID- 29349718
TI - Erratum to: The Innate Facet of the Brain: Human Neurons Express TLR3 and Sense
Viral dsRNA.
PMID- 29349719
TI - Shifts in the importance of the species pool and environmental controls of
epiphytic bryophyte richness across multiple scales.
AB - Species richness is influenced by a nested set of environmental factors, but how
do these factors interact across several scales? Our main aim is to disentangle
the relative importance of environmental filters and the species pool on the
richness of epiphytic bryophytes across spatial scales. To do so, we sampled
epiphytic bryophytes in 43 oak forests across the northwest of the Iberian
Peninsula. As predictors we used climate, descriptors of forest structure and
micro-environment. We applied structural equation modeling to relate these
variables with richness and cover at three scales: locality (forest), stand
(three stands per forest), and sample (a quadrate in a tree). We assumed top-down
relationships, so that large-scale variables influenced lower scale variables,
and in which cover directly influenced richness. Richness at the next larger
scale (locality to stand and stand to sample) is considered a surrogate of the
species pool and included as a predictor of richness at the next smaller scale.
Environmental variables explain locality richness, but as we decrease the spatial
scale, its importance decreases and the dependence on species pool increases. In
addition, we found unexpected bottom-up relationships (between micro-scale
environment to locality richness). Our results point to the scale dependence of
niche vs. neutral processes: niche processes are important at the locality
(forest) scale, while neutral processes are significant at the small (sample)
scale. We propose a modified conceptualization of the factors influencing
biodiversity at different spatial scales by adding links across different scales
(between micro-environment and locality-scale richness in our study).
PMID- 29349720
TI - Differential Effects of Formal and Informal Gambling on Symptoms of Problem
Gambling During Voluntary Self-Exclusion.
AB - Voluntary self-exclusion (VSE) programs enable problem gamblers to engage in a
break from casino-based gambling. The current study analyzed the effects of a VSE
program in British Columbia, Canada on problem gambling symptoms and the
comparative reductions in problem gambling symptoms when participants abstained
from gambling, continued to participate in non-casino based gambling, or
attempted to violate their exclusion contract. 269 participants completed two
telephone interviews over a 6-month period. Participants were administered the
Problem Gambling Severity Index (PGSI). Substantial reductions in PGSI scores
were observed after 6 months. Program violators had significantly smaller PGSI
Difference Scores by Time 2 compared to those who continued to gamble outside of
the casino and those who completely abstained from all gambling. There were no
significant differences between those who gambled informally and those who
abstained. A multiple regression identified that while access to counselling and
length of enrollment also contributed to the reduction in PGSI scores, violation
attempts were most strongly associated with smaller reductions in symptoms of
problem gambling. These results imply that some gamblers can successfully engage
in non-casino based forms of gambling and still experience reductions in symptoms
of problem gambling. Future analyses will explore characteristics associated with
group membership that may help to identify which participants can successfully
engage in non-casino based gambling without re-triggering symptoms of problem
gambling.
PMID- 29349721
TI - Effects of load on the acute response of muscles proximal and distal to blood
flow restriction.
AB - To determine the effects of load and blood flow restriction (BFR) on muscular
responses, we asked 12 participants to perform chest presses under four different
conditions [30/0, 30/40, 50/0, and 50/40, presented as percentage one-repetition
maximum (1RM)/percentage arterial occlusion pressure (AOP)]. Muscle thickness
increased pre- to post-exercise [chest: mean 0.29, 95% confidence interval (CI)
0.21, 0.37 cm; triceps: mean 0.44, 95% CI 0.34, 0.54 cm], remaining elevated for
15 min post-exercise. Electromyography amplitude was greater with 50% 1RM and
increased over time for the first three repetitions of each set of chest presses.
The last three repetitions differed across time only. AOP increased from pre- to
post-exercise, augmented by BFR [30/0: mean 31, 95% CI 18, 44 mmHg; 30/40: mean
39, 95% CI 28, 50 mmHg; 50/0: mean 32, 95% CI 23, 41 mmHg; 50/40: mean 46, 95% CI
32, 59 mmHg). Tranquility decreased and physical exhaustion increased from the
pre- to post-condition, with both parameters returning to the baseline 15 min
post-exercise level. In conclusion, load and BFR do not elicit meaningful
differences in the acute response of chest press exercise taken to failure.
PMID- 29349722
TI - Bystin (BYSL) as a possible marker of severe hypoxic-ischemic changes in
neuropathological examination of forensic cases.
AB - Bystin (BYSL) is a 306-amino acid protein encoded in humans by the BYSL gene
located on the 6p21.1 chromosome. It is conserved across a wide range of
eukaryotes. BYSL was reported to be a sensitive marker for the reactive
astrocytes induced by ischemia/reperfusion and chemical hypoxia in vitro and is
considered to be one of the common characteristics of astrogliosis. In our study
we examined whether BYSL could be used as a marker for hypoxic-ischemic changes
in forensic cases. Groups suspected of acute hypoxic-ischemic changes presented
strong BYSL expression in the cytoplasm of neocortical neurons especially in
layers 3-5, that seemed to be short-lasting. In the hypoxic-ischemic-reperfusion
group we did not find BYSL expression. BYSL expression in the cytoplasm of
cortical neurons was minimal in the control group (cardiac arrest). BYSL seems to
be a promising early marker of severe hypoxic-ischemic changes in
neuropathological examination of forensic cases and certainly requires further
studies.
PMID- 29349723
TI - Species diversity and tissue specific dispersal of necrophagous Diptera on human
bodies.
AB - In forensic entomology, many studies analyze fly activity and succession on dead
bodies by using pig cadavers and a variety of small baited traps. Data on real
human bodies are very rare. To address this shortcoming, we analyzed the fly
fauna of 51 human bodies in Germany. Sex, age, place of discovery, and presumed
time of death were noted. Larvae were sampled during autopsy according to body
region or tissue. For every infested region, the total number of fly larvae were
estimated and classified into categories of 1-10, 11-50, and 50+. All samples
were identified to the species level. Besides a descriptive analysis of their
occurrence patterns, a categorical PCA was performed, and multispecies
generalized linear models and a latent variable model were run. Our results
highlight the most forensically important blow flies on human bodies in Central
Europe (Lucilia sericata, L. ampullacea, Phormia regina, Calliphora vicina);
prove, for the first time, the general transferability of species lists based on
succession studies on pig cadavers; recommend a certain set of species, such as
the so-far neglected L. ampullacea, for future developmental studies; and reveal
competitive occurrence of up to six species on the same body as a potential
factor of influence. Assignment to a certain body region was often possible and
our data clearly indicate certain tissues, e.g. brain, as of high interest for
future developmental studies. Focusing on real scenario settings helps direct
research to forensically relevant questions and appraises the plausibility of
vital laboratory studies.
PMID- 29349724
TI - Analyzing similarities in genome sequences.
AB - This article investigates aspects of similarity between complete sequences of
mitochondrial DNA by determining the distribution of the relative frequencies of
words with different lengths and the characteristics of their relevance
throughout the sequences. The degree of similarity is obtained by comparing the
distances between words contained within these sequences. Our results indicate
that the best groupings among different species depend on the lengths of words
and their respective relative frequencies. We also observed that the longer the
word the more consistent the grouping between the sequences becomes. The
application of our results, together with the perspective of analyzing DNA
sequences belonging to a single biological species, may be important for the
construction of phylogenetic trees, which are appropriate structures for
understanding the evolutionary history of the species.
PMID- 29349725
TI - Ki67 Proliferative Index in Carcinoid Tumors Involving Ovary.
AB - Primary ovarian carcinoid tumors are rare neoplasms that constitute less than
0.1% of all ovarian carcinomas. However, carcinoid tumors metastatic to ovaries
are more common. Cell proliferative rate is an important factor in the
determination of neuroendocrine tumor prognosis. Limited data are available as
regards Ki67 proliferation index in predicting the physiological features of
carcinoid tumors involving the ovary. Pathology files of Mayo Clinic Rochester
(1995-2014) were searched, and clinical information was collected from medical
records. All cases were stained with an antibody against Ki67, and digital
analysis was performed with digital imaging analysis. A total of 36 cases (median
age 64 years, range 33-83 years), including 9 primary (median age 68 years, range
33-73 years) and 27 metastatic carcinoid cases (median age 64 years, range 36-83
years), were investigated in the current study. Seven out of nine (77.8%) primary
ovarian carcinoids are associated with mature teratoma. Twenty two metastatic
carcinoids (81.5%) were from the GI tract, four (14.8%) from the pancreas, and
one (3.7%) from the posterior thorax location. There was significant difference
of Ki67 index between primary (median 2.3%, range, 0.6-8.4%) and metastatic
carcinoid tumors (median 9.7%, range, 1.3-46.7%) (p = 0.002). The survival time
is much shorter among patients with metastatic carcinoid tumor (median survival
5.8 years) comparing to primary ovarian carcinoid tumor (median 14.2 years) (p =
0.0005). A strong association between Ki67 index and patient survival time was
identified (Hazard ratio for 1-percentage point increase 1.11, p = 0.001).
Comparing to primary ovarian carcinoid tumor, metastatic carcinoid usually
exhibits a higher Ki67 index and a worse outcome.
PMID- 29349726
TI - Fungal Respiratory Infections in Cystic Fibrosis (CF): Recent Progress and Future
Research Agenda.
PMID- 29349727
TI - Lifestyles of Patients with Functional Psychosis Compared to Those of a Sample of
the Regional General Population: Findings from a Study in a Community Mental
Health Service of the Veneto Region, Italy.
AB - Unhealthy lifestyles contribute, with other risk factors, to the high prevalence
of mortality and physical comorbidity among mental patients compared to the
general population. We collected data on the lifestyles of 193 subjects with
psychosis in contact with a Community Mental Health Service in north-eastern
Italy and compared them with a representative sample (total: 3219 subjects) of
the general population of the same region. Diet, exercise, smoking and alcohol
consumption were worse in mental patients. A higher percentage of patients was
overweight or obese. The associations between socio-demographic and lifestyles
variables showed that older patients exercise less, female patients tend to smoke
and use alcohol less, while more educated patients tend to have higher alcohol
consumption levels. Mental patients have unhealthier lifestyles and they appear
to be more refractory to recommendations than the general population, indicating
the necessity of specific health promotion programmes in this population.
PMID- 29349728
TI - Correction to: Mental Health Needs and Psychoactive Drug Use in a User Population
of the Family Health Strategy (FHS) in Ribeirao Preto, Sao Paulo, Brazil.
AB - The original version of this article unfortunately published without
acknowledgement. The funding information and grant number is given below: Funding
Research supported by Research in Public for the National Health Care System (PP
SUS), Grant number 12/51732-9.
PMID- 29349729
TI - Witnessing the advance of science and technology in life sciences in the new era.
PMID- 29349730
TI - CCN5 in alveolar epithelial proliferation and differentiation during neonatal
lung oxygen injury.
AB - Lung immaturity is the major cause of morbidity and mortality in premature
infants, especially those born <28 weeks of gestation. These infants are at high
risk of developing respiratory distress syndrome (RDS), a lung disease caused by
insufficient surfactant production and immaturity of saccular/alveolar type II
epithelial cells in the lung. RDS treatment includes oxygen and respiratory
support that improve survival but also increase the risk for bronchopulmonary
dysplasia (BPD), a chronic lung disease characterized by arrested
alveolarization, airway hyperreactivity, and pulmonary hypertension. The
mechanisms regulating normal alveolar development and how injury disrupts normal
development to cause BPD are not well understood. We examined the role of the
matricellular protein CCN5 (Cysteine-rich protein 61/Connective tissue growth
factor/Nephroblastoma-overexpressed protein) in the development of BPD. Cultured
non-proliferating alveolar type II cells expressed low levels of CCN5 protein,
and displayed higher levels during proliferation. siRNA targeting of CCN5 reduced
alveolar type II cell proliferation and migration in cell culture. In a mouse
model of hyperoxia-induced BPD, CCN5 protein was increased only in proliferating
alveolar type I cells. Alveolar epithelial cells co-expressing markers of type II
cells and type I cells also appeared. The results suggest that hyperoxic injury
in immature lungs induces proliferation of type I cells and trans-differentiation
of type II cells into type I cells. We propose that the mechanism of the injury
response in BPD includes CCN5 expression. Study of CCN5 in neonatal alveolar
injury will further our understanding of BPD pathophysiology while providing a
mechanistic foundation for therapeutic approaches.
PMID- 29349731
TI - Membranous nephropathy associated with pregnancy: an anti-phospholipase A2
receptor antibody-positive case report.
AB - Pregnancy and membranous nephropathy (MN) can occur concurrently with nephrotic
syndrome. However, the pathophysiology of MN associated with pregnancy remains
unclear, including the involvement of anti-M-type phospholipase A2 receptor
(PLA2R) antibody, the major antigen of idiopathic MN (iMN). A treatment for the
condition is also not established. We present the case of a 43-year-old pregnant
female with incidental proteinuria and hypoalbuminemia. We made a diagnosis of
nephrotic syndrome at 11 week gestation. Renal biopsy revealed iMN using
predominant granular staining of IgG4 along the glomerular basement membrane. No
secondary cause was identified. Oral glucocorticoid therapy was started from 17
week gestation and induced complete remission at 28 week gestation. A healthy
infant was born at 38 week gestation. Glucocorticoid therapy was stopped
postpartum without MN relapse. Anti-PLA2R antibody was later found to be positive
using serum reserved from before treatment. In conclusion, we presented the case
of a pregnant woman with iMN and anti-PLA2R antibodies, whose nephrotic syndrome
was successfully controlled with oral glucocorticoids to reach complete
remission, even after tapering off the medication. Pregnancy per se might be
associated with iMN onset.
PMID- 29349732
TI - Membranous glomerulonephritis with an LMNA mutation.
AB - We had encountered the case of membranous glomerulonephritis (MGN) with dilated
cardiomyopathy due to LMNA gene mutation. LMNA mutation was known as a cause of
'laminopathy' such as dilated cardiomyopathy, muscular dystrophy, neuropathy and
so on. LMNA gene might be a candidate of genetic basis in cryptogenic MGN.
PMID- 29349733
TI - Point-of-care ultrasound (POCUS) of the upper airway.
AB - Airway management is a critical skill in the practice of several medical
specialities including anesthesia, emergency medicine, and critical care. Over
the years mounting evidence has showed an increasing role of ultrasound (US) in
airway management. The objective of this narrative review is to provide an
overview of the indications for point-of-care ultrasound (POCUS) of the upper
airway. The use of US to guide and assist clinical airway management has
potential benefits for both provider and patient. Ultrasound can be utilized to
determine airway size and predict the appropriate diameter of single-lumen
endotracheal tubes (ETTs), double-lumen ETTs, and tracheostomy tubes.
Ultrasonography can differentiate tracheal, esophageal, and endobronchial
intubation. Ultrasonography of the neck can accurately localize the cricothyroid
membrane for emergency airway access and similarly identify tracheal rings for US
guided tracheostomy. In addition, US can identify vocal cord dysfunction and
pathology before induction of anesthesia. A rapidly growing body of evidence
showing ultrasonography used in conjunction with hands-on management of the
airway may benefit patient care. Increasing awareness and use of POCUS for many
indications have resulted in technologic advancements and increased accessibility
and portability. Upper airway POCUS has the potential to become the first-line
non-invasive adjunct assessment tool in airway management.
PMID- 29349734
TI - Alternative soilless media using olive-mill and paper waste for growing
ornamental plants.
AB - Peat-based growing media are not ecologically sustainable and peat extraction
threatens sensitive peatland ecosystem. In this study, olive-stone waste (OSW)
and paper waste (PW) were used in different ratios-as growing media-for
ornamental crop production, as peat (P) substitutes. Marigold (Calendula
officinalis L.), petunia (Petunia x hybrita L.) and matthiola (Matthiola incana
L.) plants were grown in (1) P (100%), (2) P:OSW (90%:10%), (3) P:OSW (70%:30%),
and (4) P:OSW:PW (60%:20%:20%). The physicochemical properties of these
substrates and the effects on plant growth were determined. The addition of 10
30% OSW into the substrate increased marigold height compared to plants grown in
100% peat. No differences in plant size, plant biomass (leaves and flowers), and
dry matter content were found. Adding PW, in combination with OSW, maintained
marigold height and total number of flowers produced to similar levels as in
plants grown in 100% peat. In matthiola, adding 30% OSW into the substrate
reduced plant size and fresh weight, but not plant height. No differences were
observed when plants grew in lower OSW (i.e., 10%) content. Petunia's height, its
total number of flowers and flower earliness (flower opening) were increased in
the presence of OSW compared to the plants grown in 100% peat. The addition of
OSW did not affect petunia's size and fresh weight among treatments. The addition
of PW suppressed several plant growth-related parameters for both matthiola and
petunia. The insertion of OSW did not change leaf chlorophyll content whereas the
presence of PW decreased chlorophylls for marigold, petunia, and matthiola. Both
OSW and PW altered the content of total phenolics and antioxidant capacity of 2,2
diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6
sulphonic acid) (ABTS) in leaves and flowers for marigold and petunia. Both 30%
OSW and PW increased antioxidative enzyme metabolism due to the increased damage
index and lipid peroxidation observed in plants. Leaf N and P content decreased
in PW-based media, while matthiola displayed visual phytotoxicity symptoms when
PW was added into the substrate. The present work indicates that up to 30% of OSW
can replace peat for marigold and petunia growing and only up to 10% of OSW for
matthiola, while the addition of PW on top of OSW is not recommended, so further
research is needed.
PMID- 29349735
TI - ICT, openness and CO2 emissions in Africa.
AB - This study investigates how information and communication technology (ICT)
complements globalisation in order to influence CO2 emissions in 44 Sub-Saharan
African countries over the period 2000-2012. ICT is measured with internet
penetration and mobile phone penetration whereas globalisation is designated in
terms of trade and financial openness. The empirical evidence is based on the
generalised method of moments. The findings broadly show that ICT can be employed
to dampen the potentially negative effect of globalisation on environmental
degradation like CO2 emissions. Practical, policy and theoretical implications
are discussed.
PMID- 29349736
TI - Application of experimental design for the optimization of artificial neural
network-based water quality model: a case study of dissolved oxygen prediction.
AB - This paper presents an application of experimental design for the optimization of
artificial neural network (ANN) for the prediction of dissolved oxygen (DO)
content in the Danube River. The aim of this research was to obtain a more
reliable ANN model that uses fewer monitoring records, by simultaneous
optimization of the following model parameters: number of monitoring sites,
number of historical monitoring data (expressed in years), and number of input
water quality parameters used. Box-Behnken three-factor at three levels
experimental design was applied for simultaneous spatial, temporal, and input
variables optimization of the ANN model. The prediction of DO was performed using
a feed-forward back-propagation neural network (BPNN), while the selection of
most important inputs was done off-model using multi-filter approach that
combines a chi-square ranking in the first step with a correlation-based
elimination in the second step. The contour plots of absolute and relative error
response surfaces were utilized to determine the optimal values of design
factors. From the contour plots, two BPNN models that cover entire Danube flow
through Serbia are proposed: an upstream model (BPNN-UP) that covers 8 monitoring
sites prior to Belgrade and uses 12 inputs measured in the 7-year period and a
downstream model (BPNN-DOWN) which covers 9 monitoring sites and uses 11 input
parameters measured in the 6-year period. The main difference between the two
models is that BPNN-UP utilizes inputs such as BOD, P, and PO43-, which is in
accordance with the fact that this model covers northern part of Serbia
(Vojvodina Autonomous Province) which is well-known for agricultural production
and extensive use of fertilizers. Both models have shown very good agreement
between measured and predicted DO (with R2 >= 0.86) and demonstrated that they
can effectively forecast DO content in the Danube River.
PMID- 29349737
TI - Teratogenic effects induced by chitosan oligosaccharide in Wistar female rat
Rattus norvegicus.
AB - The aim of this research is to investigate the teratogenic effects of chitosan
oligosaccharide in Wistar female rats (Rattus norvegicus). Chitosan LD50 value
was calculated by probit analysis. High dose, 1/10 LD50 which equal to 150 mg/kg
body weight, and low dose, 1/30 LD50 which equal to 50 mg/kg body weight, were
administrated orally to Wistar female rats to examine the teratogenic effect
during organogenesis period from 6th day to 15th day of gestation. Treated and
control rats were sacrificed and their foetuses were examined for external,
skeletal and visceral anomalies, number and length of foetuses and their weights.
Obtained results showed toxicity and teratogenic effects of chitosan on treated
rats and their progenies, i.e. high fetal mortality, offspring's weight and
length reduction, and high incidence of fetal external, skeletal and visceral
abnormalities. This suggested that chitosan is a teratogenic compound, restricted
to current results from orally treated Wistar rats.
PMID- 29349738
TI - Letter to the Editor on "Chrysotile and rock wool fibers induce chromosome
aberrations and DNA damage in V79 lung fibroblast cells".
PMID- 29349739
TI - Enhanced reductive dechlorination of 1,1,1-trichloroethane using zero-valent iron
biochar-carrageenan microspheres: preparation and microcosm study.
AB - In this study, a composite remediation material for the enhanced reductive
dechlorination (ERD) of 1,1,1-trichloroethane (1,1,1-TCA) in aqueous solution was
prepared. This material was comprised of biochar as the carrier and adsorbent,
and carrageenan (CG) as the embedding medium to entrap the organic carbon sources
and zero-valent iron (ZVI). We determined the suitable biochar dosage and organic
carbon source in the composite alongside the optimal preparation conditions.
Furthermore, using an anaerobic microcosm study, we discussed the performance and
possible mechanisms of the composite on 1,1,1-TCA removal in aqueous solution.
From this, we found that the suitable dosage of biochar in water during the
preparation of composite microspheres was 0.2% (w/v). Under this condition, the
biochar had a strong capacity to adsorb 1,1,1-TCA with a removal efficiency of
84.2%. Soluble starch was selected as the appropriate organic carbon source,
because starch-microspheres show an excellent slow-release effect in water. The
optimal preparation conditions of microspheres were identified as follows: 2% CG
(w/v) colloidal solution, 6% CaCl2 (w/v) solution, and a 12-h curing time. After
25-day incubation with the composite prepared under optimized conditions, the
removal efficiency of 1,1,1-TCA was 95.68%, which was 24.69% higher than that
observed in the microcosm with a commercial remediation material. The scanning
electron microscopy (SEM) images show that the amounts of ZVI and soluble starch
inside the microsphere decreased obviously, while the biochar amount remained
about the same. This indicates that 1,1,1-TCA in aqueous solution was mainly
removed via soluble starch-enhanced biotic reductive dechlorination and ZVI
enhanced abiotic reductive dechlorination. The changes in microbial community
structure demonstrate that the composite stimulated the activities of functional
anaerobic bacteria, in particular, regarding dechlorination and fermentation
abilities in the microcosm, therefore enhancing the anaerobic biodegradation of
1,1,1-TCA. This study suggests that the composite, entrapping biochar, ZVI, and
organic carbon source in CG microspheres can significantly enhance the reductive
dechlorination of 1,1,1-TCA in aqueous solution. We anticipate this novel
remediation material could be successfully applied to the in situ ERD remediation
of natural groundwater mainly contaminated with 1,1,1-TCA.
PMID- 29349740
TI - Can Cd translocation in Oryza sativa L. be attenuated by arbuscular mycorrhizal
fungi in the presence of EDTA?
AB - Arbuscular mycorrhizal (AM) fungi play an important role in plant tolerance of
heavy metal contamination. In this study, a pot experiment was conducted to
illustrate the effects of the two AM fungi species Funneliformis mosseae (Fm) and
Rhizophagus irregularis (Ri) on plant growth of Oryza sativa L. either with or
without ethylenediamine tetraacetate (EDTA) addition and during exposure to five
Cd concentrations (in the range of 0-5 mg kg-1). The results showed that Fm
inoculation achieved greater mycorrhizal colonization and mycorrhizal dependency
indexes than Ri inoculation. In addition, the effects of AM fungi on Cd
biosorption and translocation in rice were also investigated in the presence of
EDTA. Despite cooperative adsorption, the Freundlich isotherm could describe the
biosorption effects of Cd on rice roots regardless of AM fungi inoculation or
EDTA addition. Cd concentrations in mycorrhizal roots increased but decreased in
mycorrhizal shoots in contrast to the control treatment. Although EDTA addition
negatively inhibited the uptake of Cd to mycorrhizal shoots, lower translocation
factor (TF) and bioconcentration factor (BCF) were still observed in treatments
with EDTA compared to control treatment. Our findings suggest that Ri and Fm
inoculation enhanced Cd immobilization in the roots, thus preventing Cd entry
into the food chain during exposure to low and high Cd stress, respectively.
PMID- 29349741
TI - Degradation behavior of triclosan by co-exposure to chlorine dioxide and UV
irradiation: influencing factors and toxicity changes.
AB - This study investigated the transformation of triclosan (TCS) following co
exposure to UV irradiation and ClO2. Special attention was given to understand
the influencing of water quality parameters and toxicity changes during the co
exposure process. The results show that the co-exposure process prompted TCS
elimination quickly and effectively, with more than 99% of TCS degraded under the
experimental conditions. The molar yield ratios of 2,4-dichlorophenol/TCS (2,4
DCP/TCS) were calculated to be 35.81-74.49%; however, the by-product of 2,8
dichlorodibenzop-dioxin (2,8-Cl2DD) was not detected. The TCS degradation was
sensitive to ClO2 dosage, pH, H2O2, and natural organic matter (NOM), but not to
the carbonate (CO32-) concentration. Neutral and slightly alkaline condition were
favorable to TCS elimination. The TCS removal rate increased from 85.33 to 99.75%
when the ClO2 concentration increased from 0.25 to 1.5 mg L-1. TCS degradation
can be promoted at low NOM level (1, 3, and 5 mg L-1), whereas was inhibited at
high NOM concentrations of 7 and 9 mg L-1. While adding H2O2, the degradation
rate of TCS increased with increasing H2O2 concentration from 1 to 3 mg L-1;
however, too low or overdosed H2O2 (0.5 and 5 mg L-1) hindered TCS degradation.
Based on the results of a microtox bioassay, the toxicity did not change
following the co-exposure process.
PMID- 29349742
TI - Treatment of persistent organic pollutants in wastewater using hydrodynamic
cavitation in synergy with advanced oxidation process.
AB - Persistent organic pollutants (POPs) are very tenacious wastewater contaminants.
The consequences of their existence have been acknowledged for negatively
affecting the ecosystem with specific impact upon endocrine disruption and
hormonal diseases in humans. Their recalcitrance and circumvention of nearly all
the known wastewater treatment procedures are also well documented. The reported
successes of POPs treatment using various advanced technologies are not without
setbacks such as low degradation efficiency, generation of toxic intermediates,
massive sludge production, and high energy expenditure and operational cost.
However, advanced oxidation processes (AOPs) have recently recorded successes in
the treatment of POPs in wastewater. AOPs are technologies which involve the
generation of OH radicals for the purpose of oxidising recalcitrant organic
contaminants to their inert end products. This review provides information on the
existence of POPs and their effects on humans. Besides, the merits and demerits
of various advanced treatment technologies as well as the synergistic efficiency
of combined AOPs in the treatment of wastewater containing POPs was reported. A
concise review of recently published studies on successful treatment of POPs in
wastewater using hydrodynamic cavitation technology in combination with other
advanced oxidation processes is presented with the highlight of direction for
future research focus.
PMID- 29349743
TI - Chemically and size-resolved particulate matter dry deposition on stone and
surrogate surfaces inside and outside the low emission zone of Milan: application
of a newly developed "Deposition Box".
AB - The collection of atmospheric particles on not-filtering substrates via dry
deposition, and the subsequent study of the particle-induced material decay, is
trivial due to the high number of variables simultaneously acting on the
investigated surface. This work reports seasonally resolved data of chemical
composition and size distribution of particulate matter deposed on stone and
surrogate surfaces obtained using a new method, especially developed at this
purpose. A "Deposition Box" was designed allowing the particulate matter dry
deposition to occur selectively removing, at the same time, variables that can
mask the effect of airborne particles on material decay. A pitched roof avoided
rainfall and wind variability; a standardised gentle air exchange rate ensured a
continuous "sampling" of ambient air leaving unchanged the sampled particle size
distribution and, at the same time, leaving quite calm condition inside the box,
allowing the deposition to occur. Thus, the "Deposition Box" represents an
affordable tool that can be used complementary to traditional exposure systems.
With this system, several exposure campaigns, involving investigated stone
materials (ISMs) (Carrara Marble, Botticino limestone, Noto calcarenite and
Granite) and surrogate (Quartz, PTFE, and Aluminium) substrates, have been
performed in two different sites placed in Milan (Italy) inside and outside the
low emission zone. Deposition rates (30-90 MUg cm-2 month-1) showed significant
differences between sites and seasons, becoming less evident considering long
period exposures due to a positive feedback on the deposition induced by the
deposited particles. Similarly, different stone substrates influenced the
deposition rates too. The collected deposits have been observed with optical and
scanning electron microscopes and analysed by ion chromatography. Ion deposition
rates were similar in the two sites during winter, whereas it was greater outside
the low emission zone during summer and considering the long-period exposure. The
dimensional distribution of the collected deposits showed a significant presence
of fine particles in agreement with deposition rate of the ionic fraction. The
obtained results allowed to point out the role of the fine particles fraction and
the importance of making seasonal studies.
PMID- 29349746
TI - A Tribute to Professor Satimaru Seno.
PMID- 29349744
TI - Alleviation of iron toxicity in Schinus terebinthifolius Raddi (Anacardiaceae) by
humic substances.
AB - One of the industrial pillars of Espirito Santo state, South East of Brazil, is
iron-mining products processing. This activity brings to a high level of coastal
pollution due to deposition of iron particulate on fragile ecosystems as
mangroves and restinga. Schinus therebinthifolius (aroeira) is a widespread
restinga species. This work tested iron toxicity alleviation by vermicompost
humic substances (HS) added to aroeira seedlings in hydroponic conditions.
Catalase, peroxidase, and ascorbate peroxidase are antioxidant enzymes that work
as reactive oxygen species (ROS) scavengers: they increase their activity as an
answer to ROS concentration rise that is the consequence of metal accumulation or
humic substance stimulation. S. terebinthifolius seedlings treated with HS and Fe
augmented their antioxidant enzyme activities significantly less than seedlings
treated separately with HS and Fe; their significantly lower Fe accumulation and
the slight increase of root and leaf area confirm the biostimulating effect of HS
and their role in blocking Fe excess outside the roots. The use of HS can be
useful for the recovery of areas contaminated by heavy metals.
PMID- 29349747
TI - A Tribute to the Memory of Hisamaru Hirai, MD, PhD Professor of the Department of
Hematology and Oncology Graduate School of Medicine, The University of Tokyo.
PMID- 29349749
TI - Thrombosis and Thromboembolism.
PMID- 29349750
TI - In Memoriam.
PMID- 29349751
TI - Myelodysplastic Syndromes and Secondary Acute Myelogeneous Leukemia: Directions
for the New Millennium.
PMID- 29349752
TI - Tumor Angiogenesis and Microcirculation.
PMID- 29349753
TI - Expensive care? Resource-based thresholds for potentially inappropriate treatment
in intensive care.
AB - In intensive care, disputes sometimes arise when patients or surrogates strongly
desire treatment, yet health professionals regard it as potentially
inappropriate. While professional guidelines confirm that physicians are not
always obliged to provide requested treatment, determining when treatment would
be inappropriate is extremely challenging. One potential reason for refusing to
provide a desired and potentially beneficial treatment is because (within the
setting of limited resources) this would harm other patients. Elsewhere in public
health systems, cost effectiveness analysis is sometimes used to decide between
different priorities for funding. In this paper, we explore whether cost
effectiveness could be used to determine the appropriateness of providing
intensive care. We explore a set of treatment thresholds: the probability
threshold (a minimum probability of survival for providing treatment), the cost
threshold (a maximum cost of treatment), the duration threshold (the maximum
duration of intensive care), and the quality threshold (a minimum quality of
life). One common objection to cost-effectiveness analysis is that it might lead
to rationing of life-saving treatment. The analysis in this paper might be used
to inform debate about the implications of applying cost-effectiveness thresholds
to clinical decisions around potentially inappropriate treatment.
PMID- 29349754
TI - Strategies to Maintain Fertility in Young Breast Cancer Patients.
AB - Breast cancer is the most frequently occurring cancer in women of reproductive
age. Treatments for breast cancer may eliminate or diminish fertility, making
discussions about fertility preservation essential prior to initiation of
gonadotoxic therapies. Additionally, even in patients who do not require
chemotherapy, the use of adjuvant endocrine therapy will often push patients out
of the reproductive window before treatment is completed. The only established
methods for fertility preservation are oocyte or embryo cryopreservation, but
experimental methods, such as ovarian suppression with GnRH agonists and ovarian
tissue cryopreservation, show great promise. Early referral to a fertility
specialist for interested patients affords patients the most fertility
preservation options, with only minimal delay to cancer treatment.
PMID- 29349755
TI - Adjuvant Endocrine Therapy.
AB - The use of hormonal therapy in breast cancer has improved the overall outcome for
patients with early-stage hormone receptor-positive disease. The choice of
hormone therapy is related to multiple factors, including menopausal state,
patient preference, and potential side effects. Molecular profiling has allowed
therapy to be tailored for an individual patient to some extent. However, further
molecular studies are needed to individualize the choice and length of adjuvant
hormone therapy. Ongoing studies are evaluating the role of additional targeted
therapies, such as CDK4/6 inhibitors, to further improve outcome for patients
with early-stage hormone receptor-positive breast cancer.
PMID- 29349756
TI - Breast Cancer Screening: The Debate that Never Ends.
AB - Screening mammography has been shown to decrease breast cancer deaths through
randomized controlled trials. However, there remains significant debate
surrounding the most appropriate time to commence screening and the optimal
screening interval. Several national organizations have recently updated their
guidelines by reanalyzing the published data. Interestingly, each organization
has come to different conclusions regarding their recommendation for breast
cancer screening in the average risk woman. Three of the main organizations that
issue guidelines for breast cancer screening in the United States are reviewd in
this chapter.
PMID- 29349757
TI - Management of the Axilla in Early Breast Cancer.
AB - Management of the axilla in early breast cancer patients has significantly
evolved in the last several decades. With the arrival of the sentinel lymph node
biopsy, surgical practice for axillary staging in patients with early breast
cancer has become gradually less invasive and formal axillary lymph node
dissection has been confined to selected patients. Over the last two decades,
evidence from randomized clinical trials have allowed for the de-escalation of
axillary surgery in the management of early stage breast cancer. Advances in the
staging and treatment of the axilla constitute a key component in determining
initial surgical planning and therapeutic strategies in the treatment of early
breast cancer. This chapter provides an updated review on the history, evolution,
and current practices for axillary management in patients with early breast
cancer, with particular attention to the surgical recommendations and
controversial scenarios of the evolving management of the axilla.
PMID- 29349758
TI - Is DCIS Overrated?
AB - Ductal carcinoma in situ (DCIS), the noninvasive form of breast cancer (BC),
comprises just over 20% of breast cancer cases diagnosed each year in the USA.
Most patients are treated with local excision of the disease followed by whole
breast radiation therapy. Total mastectomy is not an uncommon approach, and total
mastectomy with a contralateral risk-reducing mastectomy has been on the rise in
the past decade. In estrogen receptor-positive disease, patients are often
offered endocrine ablative therapy with a selective estrogen receptor modulator
or an aromatase inhibitor as both treatment and prevention. Local regional
treatment options have no impact upon ultimate overall survival. Long-term
survival rates are higher in patients with DCIS than with any other form of the
disease. Are these strikingly high success rates a testament to effective
treatment strategies or is there a significant subset of DCIS that was unlikely
to ever progress to invasive ductal carcinoma? DCIS was not seen in the US prior
to the advent of screening mammography. When compared to other countries, the USA
has the highest utilization of screening mammography and the incidence rate of
DCIS. Other lines of evidence include autopsy series examining the breast tissue
of women who died of other causes, missed-diagnosis series and current
retrospective reviews of DCIS, all align in support of the concept of DCIS as
indolent in the majority of cases [3-14]. The evidence suggests that both patient
and physician misconceptions about DCIS have led to overdiagnosis and over
treatment of DCIS. Recently, a gene expression profiling tool (12 gene assay,
Oncotype DCIS) has emerged that shows considerable promise in predicting class in
DCIS patients.
PMID- 29349759
TI - Readdressing the Role of Surgery of the Primary Tumor in de Novo Stage IV Breast
Cancer.
AB - The impressive advances in breast cancer treatment observed in recent years also
apply to the metastatic setting, where a subset of patients with favorable
metastatic disease enjoy long-term survival with systemic therapy. In patients
with distant disease, the primary tumor in the breast has not classically been
though to merit specific locoregional therapy. However, about 6% of Stage IV
patients in the USA and up to 20% in limited resource environments present with
synchronous distant metastases at the time of initial diagnosis. For this group,
who have an intact primary tumor, retrospective studies suggest that local
therapy for the primary site may be beneficial. However, these retrospective
analyses are biased in that women receiving local therapy to the primary site
were younger and had biologically favorable tumors and lower volume metastatic
disease. Two completed randomized clinical trials have shown conflicting results,
and others are ongoing. In this chapter, we discuss the results of these studies
through the present day and summarize their conclusions and their implications
for clinical management.
PMID- 29349760
TI - Advancements and Personalization of Breast Cancer Treatment Strategies in
Radiation Therapy.
AB - Significant technologic advances in radiation treatment delivery now allow for
more personalized delivery considerations which incorporate individual patient
characteristics (such as tumor location and patient anatomy) and more precise
delivery in the breast conservation or post-mastectomy setting. The combined
advancements with other treatment modalities (i.e., systemic therapy, surgical
management) have had direct effects on local-regional management and outcomes
such that currently, local-regional relapses after definitive treatment for
localized disease are now rarely experienced. Recent advances in the radiation
therapy field have come from careful patient selection for a variety of three
dimensional treatment delivery techniques and alternatives to conventional
tangential radiation. These advances have been demonstrated to diminished
acute/long-term toxicity, minimized dose to surrounding normal tissue structures
such as the heart and lung, and ultimately result in an improvement in the
therapeutic ratio for radiation treatment. This chapter discusses recent
radiation innovations and appropriate patient selection for their application,
for a more personalized approach to radiation therapy for breast cancer patients.
PMID- 29349761
TI - Multi-gene Panel Testing in Breast Cancer Management.
AB - Hereditary predisposition accounts for approximately 10% of all breast cancers
and is mostly associated with germline mutations in high-penetrance genes
encoding for proteins participating in DNA repair through homologous
recombination (BRCA1 and BRCA2). With the advent of massive parallel next
generation DNA sequencing, simultaneous analysis of multiple genes with a short
turnaround time and at a low cost has become possible. The clinical validity and
utility of multi-gene panel testing is getting better characterized as more data
on the significance of moderate-penetrance genes are collected from large, cancer
genetic testing studies. In this chapter, we attempt to provide a general guide
for interpretation of panel gene testing in breast cancer and use of the
information obtained for clinical decision-making.
PMID- 29349762
TI - Advances in Endocrine Therapy for Postmenopausal Metastatic Breast Cancer.
AB - A majority of breast cancers are hormone receptor (HR) positive and are
responsive to various types of hormone manipulation. Endocrine therapy is the
preferred first-line therapy for patients with advanced estrogen receptor (ER)
positive, HER2-negative breast cancer who do not have symptomatic visceral
disease. Endocrine therapy is often continued in the second- and third-line
setting, with chemotherapy deferred until tumor becomes endocrine therapy
refractory and/or a visceral crisis in imminent. Therapeutic options vary based
on clinical presentation and include single-agent therapies such as tamoxifen,
aromatase inhibitors and fulvestrant, and combination therapies options. Over the
past few years, multiple trials have shown significant improvement in outcomes
when endocrine therapy is combined with CDK 4/6 inhibitors or mTOR inhibitors.
Improved efficacy comes at a cost of a modest increase in toxicity. Mechanisms of
ER resistance have been defined leading to multiple strategies to improve
efficacy and overcome resistance. These include the combination therapies options
mentioned above and other novel drugs that are in development. This review will
summarize the existing literature regarding endocrine therapy in postmenopausal
metastatic breast cancer and outline treatment approaches in the first-line
metastatic setting and beyond.
PMID- 29349763
TI - Immune Checkpoint Blockade for Breast Cancer.
AB - An effective antitumor immune response requires interaction between cells of the
adaptive and innate immune system. Three key elements are required: generation of
activated tumor-directed T cells, infiltration of activated T cells into the
tumor microenvironment, and killing of tumor cells by activated T cells. Tumor
immune evasion can occur as a result of the disruption of each of these three key
T cell activities, resulting in three distinct cancer-immune phenotypes. The
immune inflamed phenotype, characterized by the presence of a robust tumor immune
infiltrate, suggests impaired activated T cell killing of tumor cells related to
the presence of inhibitory factors. Programmed death receptor-1 (PD-1) is an
inhibitory transmembrane protein expressed on T cells, B cells, and NK cells. The
interaction between PD-1 and its ligands (PD-L1/L2) functions as an immune
checkpoint against unrestrained cytotoxic T effector cell activity-it promotes
peripheral T effector cell exhaustion and conversion of T effector cells to
immunosuppressive T regulatory (Treg) cells. Immune checkpoint inhibitors, which
block the PD-1/PD-L1 axis and reactivate cytotoxic T effector cell function, are
actively being investigated for the treatment of breast cancer.
PMID- 29349765
TI - Issues in stem cells in Asia and SNAP decisions.
PMID- 29349764
TI - Sexual Function Post-Breast Cancer.
AB - The consequences of estrogen deprivation and therapeutic interventions such as
radiation, chemotherapy and surgery have a significant negative impact on libido,
sexual arousal, orgasmic function and the ability to have pleasurable
intercourse. Evaluation and treatment of female sexual dysfunction is a
significant unmet need in the breast cancer survivor in spite of the availability
of safe and effective treatments.
PMID- 29349766
TI - Constant existence of the sensory branch of the nerve to the pyramidalis
distributing to the upper margin of the pubic ramus.
AB - Twenty-one sides of 11 adult Japanese cadavers were investigated, and 2 of 21
sides exhibited absence of the pyramidalis. We observed that all of the nerves to
the pyramidalis included the sensory nerve branch, which distributed to the
aponeurotic tissue in the upper area of the pubic ramus. To investigate the
clinical relevance and developmental process of the pyramidalis, detailed
innervation patterns of the pyramidalis and the lumber plexus were examined and
compared with the case of absent pyramidalis. The nerves to the pyramidalis could
be classified into five types by the derivative nerves and two subtypes by their
courses associated with the funiculus spermaticus. In the cases of absent
pyramidalis, similar sensory branches distributed close to the upper area of the
pubic ramus. We deduced that the sensory branch extended along with the muscular
branch to the pyramidalis after development of the pyramidalis and that only the
sensory branch remained in cases in which the pyramidalis disappeared. The two
subtypes might associate with descensus testis. Surgeons performing inguinal
hernia repair using a mesh and tension-free surgical technique should preserve
the nerves around the funiculus spermaticus to avoid diminished proprioception in
the lower abdominal wall.
PMID- 29349768
TI - GCN2 deficiency protects mice from denervation-induced skeletal muscle atrophy
via inhibiting FoxO3a nuclear translocation.
PMID- 29349769
TI - Examining Character Structure and Function Across Childhood and Adolescence.
AB - Character strengths are an integral component of positive youth development that
can promote flourishing. Developmental principles posit constructs become
increasingly complex with age, yet this process has not been examined with
character. Using a socioeconomically and ethnically diverse sample of 2,467 youth
ages 9-19, bifactor models were estimated across elementary, middle, and high
school-age groups to examine age differences in character structure and function.
With successive age, a greater number of specific character strength factors were
identified, suggesting character structure becomes more differentiated across
adolescence. Results linking character bifactor models to indicators of positive
functioning also supported differentiation in character function across ages.
Findings point to the need for theoretical and empirical considerations of
character structure and function across development.
PMID- 29349770
TI - Retrospective audit of patients referred for further treatment following Mohs
surgery for non-melanoma skin cancer.
AB - BACKGROUND/OBJECTIVES: To describe the characteristics, subsequent management and
outcomes of patients referred for further management following Mohs micrographic
surgery (MMS) for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).
METHODS: Retrospective analysis of patients referred to a quaternary cancer
centre from 2000 to 2015. RESULTS: In total, 83 lesions in 82 patients were
referred for further management; 52 (62%) were SCC and 80 (96%) were located in
the head and neck. Reasons for referral included high-risk disease for
consideration for adjuvant radiotherapy (37/83, 45%), inadequate resection
(28/83, 34%) or recurrence following previous MMS (15/83, 17%). Fewer than 40% of
the 69 referrals received from MMS surgeons included photos or an operative
report and diagram. There was discordance in pathology opinion in 11 (13%) of
cases. Histopathology from MMS was reviewed in eight cases and there was
discordance with the in-hospital pathology opinion in six of these. In-hospital
re-excision was performed in 19 cases and in five of these the pathology report
on the paraffin-sectioned re-excised tissue was discordant with prior MMS
assessment. Significantly, two cases were associated with a misinterpretation of
lymphocytic infiltrate as residual disease in patients with chronic lymphocytic
leukaemia (CLL). CONCLUSION: This study highlights some of the challenges and
limitations of MMS. Early referral for multidisciplinary management is
recommended when MMS resection margins are inadequate or uncertain, especially
for high-risk SCC. We recommend that referrals be accompanied by histological
material, as well as a detailed report with operative photos and diagrams. CLL
can pose an intraoperative diagnostic challenge. Discrepancies in the
interpretation of MMS slides present an opportunity for improvement, and our
findings support the role of ongoing quality assurance programs.
PMID- 29349771
TI - CYP2D6 Protein Level Is the Major Contributor to Interindividual Variability in
CYP2D6-Mediated Drug Metabolism in Healthy Human Liver Tissue.
AB - CYP2D6 genetic polymorphisms are considered a major contributor to the large
interindividual variability in CYP2D6-mediated drug metabolism, but fail to
explain a significant portion of the variability. The aim of this study was to
assess the ability of the CYP2D6 activity score (AS) estimated from CYP2D6
genotype to predict CYP2D6 expression and enzyme activity. The CYP2D6 gene region
was sequenced in 115 healthy human liver tissue samples to determine their CYP2D6
AS. Additionally, CYP2D6 enzyme activity, protein, and mRNA levels were
estimated. CYP2D6 AS explained 23% of the interindividual variability in CYP2D6
activity, but only 7.5% in tissues assigned AS 1-2. The CYP2D6 protein level was
found to be the major determinant of CYP2D6 activity, explaining 59% of
variability. These findings suggest that while CYP2D6 AS is a good predictor of
poor metabolizer phenotype, additional nongenetic factors may govern the rate of
CYP2D6-mediated metabolism in those without the poor metabolizer phenotype.
PMID- 29349772
TI - Does the Use of Diagnostic Technology Reduce Fetal Mortality?
AB - OBJECTIVE: To examine the effect that the introduction of new diagnostic
technology in obstetric care has had on fetal death. DATA SOURCE: The Medical
Birth Registry of Norway provided detailed medical information for approximately
1.2 million deliveries from 1967 to 1995. Information about diagnostic technology
was collected directly from the maternity units, using a questionnaire. STUDY
DESIGN: The data were analyzed using a hospital fixed-effects regression with
fetal mortality as the outcome measure. The key independent variables were the
introduction of ultrasound and electronic fetal monitoring at each maternity
ward. Hospital-specific trends and risk factors of the mother were included as
control variables. The richness of the data allowed us to perform several
robustness tests. PRINCIPAL FINDING: The introduction of ultrasound caused a
significant drop in fetal mortality rate, while the introduction of electronic
fetal monitoring had no effect on the rate. In the population as a whole,
ultrasound contributed to a reduction in fetal deaths of nearly 20 percent. For
post-term deliveries, the reduction was well over 50 percent. CONCLUSION: The
introduction of ultrasound made a major contribution to the decline in fetal
mortality at the end of the last century.
PMID- 29349773
TI - Progestin-only and combined oral contraceptives and receptor-defined
premenopausal breast cancer risk: The Norwegian Women and Cancer Study.
AB - Receptor-defined subtypes of breast cancer represent distinct cancer types and
have differences in risk factors. Whether the two main hormonal forms of oral
contraceptives (OCs); i.e. progestin-only (POC) and combined oral contraceptives
(COC), are differentially associated with these subtypes are not well known. The
aim of our study was to assess the effect of POC and COC use on hormone receptor
defined breast cancer risk in premenopausal women in a prospective population
based cohort - The Norwegian Women and Cancer Study (NOWAC). Information on OC
use was collected from 74,862 premenopausal women at baseline. Updated
information was applied when follow-up information became available. Multiple
imputation was performed to handle missing data, and multivariable Cox regression
models were used to calculate hazard ratios (HR) for breast cancer. 1,245
incident invasive breast cancer cases occurred. POC use >=5 years was associated
with ER+ (HR = 1.59, 95% CI 1.09- 2.32, ptrend = 0.03) and ER+/PR+ cancer (HR =
1.63, 95% CI 1.07-2.48, ptrend = 0.05), and was not associated with ER-
(pheterogeneity = 0.36) or ER-/PR- (pheterogeneity = 0.49) cancer. COC use was
associated with ER- and ER-/PR- cancer, but did not increase risk of ER+ and
ER+/PR+ cancer. Current COC use gave different estimates for ER/PR-defined
subtypes (pheterogeneity = 0.04). This is the first study to show significant
associations between POC use and hormone receptor-positive breast cancer. The
lack of power to distinguish effects of POC use on subtype development calls for
the need of larger studies to confirm our finding.
PMID- 29349774
TI - The vaccine adjuvant alum promotes IL-10 production that suppresses Th1
responses.
AB - The effectiveness of many vaccines licensed for clinical use relates to the
induction of neutralising antibodies, facilitated by the inclusion of vaccine
adjuvants, particularly alum. However, the ability of alum to preferentially
promote humoral rather than cellular, particularly Th1-type responses, is not
well understood. We demonstrate that alum activates immunosuppressive mechanisms
following vaccination, which limit its capacity to induce Th1 responses. One of
the key cytokines limiting excessive immune responses is IL-10. Injection of alum
primed draining lymph node cells for enhanced IL-10 secretion ex vivo. Moreover,
at the site of injection, macrophages and dendritic cells were key sources of IL
10 expression. Alum strongly enhanced the transcription and secretion of IL-10 by
macrophages and dendritic cells. The absence of IL-10 signalling did not
compromise alum-induced cell infiltration into the site of injection, but
resulted in enhanced antigen-specific Th1 responses after vaccination. In
contrast to its decisive regulatory role in regulating Th1 responses, there was
no significant change in antigen-specific IgG1 antibody production following
vaccination with alum in IL-10-deficient mice. Overall, these findings indicate
that injection of alum promotes IL-10, which can block Th1 responses and may
explain the poor efficacy of alum as an adjuvant for inducing protective Th1
immunity.
PMID- 29349775
TI - The association between borderline pre-operative anaemia in women and outcomes
after cardiac surgery: a cohort study.
AB - Anaemia is common before cardiac surgery and is associated with increased
morbidity and mortality. The World Health Organization (WHO) definition of
anaemia is lower for women than for men by 10 g.l-1 , potentially putting women
at a disadvantage compared with men with regard to pre-operative optimisation.
Our hypothesis was that women with borderline anaemia (defined by us as
haemoglobin concentration 120-129 g.l-1 ) would have a higher rate of red cell
transfusion, morbidity and mortality than non-anaemic women (haemoglobin >= 130
g.l-1 ). This retrospective observational study included all adult patients
admitted for elective cardiac surgery from January 2013 to April 2016. During the
study period, 1388 women underwent cardiac surgery. Pre-operatively, 333 (24%)
had a haemoglobin level < 120 g.l-1 ; 408 (29%) 120-129 g.l-1 ; and 647 (47%) >=
130 g.l-1 . Compared with non-anaemic women, women with borderline anaemia were
more likely to be transfused (68.6% vs. 44.5%; RR 1.5, 95%CI 1.4-1.7; p < 0.0001)
and were transfused with more units of red cells, mean (SD) 1.8 (2.8) vs. 1.3
(3.0); p < 0.0001. Hospital length of stay was significantly longer in the
borderline anaemia group compared with non-anaemic women, median (IQR [range]) 8
(6-12 [3-45]) vs. 7 (6-11 [4-60]); p = 0.0159. Short- and long-term postoperative
survival was comparable in both groups. Borderline anaemia is associated with
increased red cell transfusion and prolonged hospital stay. Future research
should address whether correction of borderline anaemia results in improved
outcomes.
PMID- 29349776
TI - Effect of palpable vs. impalpable cricothyroid membranes in a simulated emergency
front-of-neck access scenario.
AB - The Difficult Airway Society 2015 guidelines recommend and describe in detail a
surgical cricothyroidotomy technique for the can't intubate, can't oxygenate
(CICO) scenario, but this can be technically challenging for anaesthetists with
no surgical training. Following a structured training session, 104 anaesthetists
took part individually in a simulated can't intubate, can't oxygenate event using
simulation and airway models to evaluate how well they could perform these front
of-neck access techniques. Main outcomes measures were: ability to correctly
perform the technical steps; procedural time; and success rate. Outcomes were
compared between palpable and impalpable cricothyroid membrane scenarios.
Anaesthetists' technical abilities were good, as assessed by a video analysis
checklist score. Mean (SD) procedural time was 44 (16) s and 65 (17) s for the
palpable and impalpable cricothyroid membrane models, respectively (p <= 0.001).
First-pass tracheal tube placement was obtained in 103 out of the 104 palpable
cricothyroidotomies and in 101 out of the 104 impalpable cricothyroidotomies (p =
0.31). We conclude that anaesthetists can be trained to perform surgical front-of
neck access to an acceptable level of competence and speed when assessed using a
simulator.
PMID- 29349777
TI - In-bed cycling in the ICU; patient safety and recollections with motivational
effects.
AB - BACKGROUND: In-bed cycling (IBC) is gaining interest for implementation in
intensive care units. Our main objective was to explore patient recollections and
experiences of early mobilization, including IBC. Secondly, we aimed to examine
if IBC was safe and feasible. METHODS: Eleven participants were interviewed about
their experiences during their critical illnesses and active mobilization in the
intensive care unit. The interviews were analyzed thematically. Six participants
were also monitored for physiological reactions and adverse events during IBC
while mechanically ventilated. RESULTS: From the interviews, one main theme with
three subthemes was identified. The main theme was: Early mobilization gave a
direction toward normalization. The three subthemes were: (1) IBC gave a feeling
of control over recovery early on during the critical illness (2) Early
mobilization, including IBC, with continuous support from health care
professionals gave a feeling of safety and hope for recovery for the patient; and
(3) Unpleasant experiences and disorientation were felt during the critical
illness and IBC. Furthermore, IBC did not induce large physiological changes or
major adverse events in the participants who were monitored for feasibility and
safety. CONCLUSIONS: Patient interviews indicated that the patients'
participation in early mobilization with emphasis on IBC motivated them to be
active in their recovery to regain a good level of health after their earlier
critical illness during their intensive care stay. IBC was, in this small study,
safe and feasible in the two participating intensive care units.
PMID- 29349778
TI - Intrathecal baclofen therapy in children: an analysis of individualized goals.
AB - AIM: To determine whether intrathecal baclofen (ITB) therapy improves performance
and performance satisfaction in goal areas identified by patients' parents.
METHOD: This study formed part of an ongoing multicentre national audit involving
six paediatric ITB pump implant centres across Australia. The Canadian
Occupational Performance Measure was the primary outcome measure utilized at
baseline, 6 months, and 12 months after pump implants in paediatric patients
receiving ITB therapy for the first time between 31st December 2009 and 31st
December 2014. RESULTS: Twenty-five children had goals identified (mean age 11y
1mo), 19 had a diagnosis of cerebral palsy and 22 were at Gross Motor Function
Classification System level IV, V, or equivalent. Strong evidence for an
improvement in goal performance (2.33, 95% CI 1.70, 2.96, p<0.001) and
performance satisfaction scores (3.08, 95% CI 2.28, 3.88, p<0.001) were
demonstrated at 6 months, compared to baseline. The differences were clinically
significant and were sustained to 12 months. INTERPRETATION: ITB therapy in
paediatric patients with hypertonia results in clinically significant
improvements in average performance and performance satisfaction scores. WHAT
THIS PAPER ADDS: The most commonly identified goals of parents of children
treated with intrathecal (ITB) therapy were: improving ease of dressing,
positioning, and transfers. ITB therapy is effective in improving performance and
performance satisfaction in children with hypertonia. Score improvements are
mainly evident within the first 6 months of therapy.
PMID- 29349779
TI - Skeletogenesis in the Persian sturgeon Acipenser persicus and its correlation
with gene expression of vitamin K-dependent proteins during larval development.
AB - The present study describes morphological development of the skeleton in the
Persian sturgeon Acipenser persicus and discusses the hypothesis that expression
of genes encoding vitamin K-dependent proteins (VKDP) might be correlated with
the mineralization of skeletal tissues during early development in sturgeons.
Results showed that development of cartilage started just after hatching (mean +/
S.D., 10.9 +/- 0.7 mm in total length, LT ) in the head and notochord, whereas
the first signs of mineralization occurred in the dentary and in the
dermopalatine and palatopterygoid elements of the upper jaw, coinciding with the
onset of exogenous feeding (20.1 +/- 1.5 mm LT ). All branchial arch elements
developed between 19.3 and 22.3 mm LT , whereas mineralization was only observed
in tooth plates associated with the hypobranchial 1 and gill rakers at 20.8 +/-
1.5 mm LT and 48.4 +/- 6.4 mm LT , respectively. Quantitative real-time PCR
showed that transcripts of VKDP genes including bone Gla protein (bgp), matrix
Gla protein (mgp) and Gla rich protein (grp) genes were significantly up
regulated during the transition to exogenous feeding, supporting hypotheses about
relevance of the above-mentioned genes in chondrogenesis at early developmental
stages. The strong mineralization of skeletal elements from 21.5 to 27.3 mm LT
(20 days post hatch) was in accordance with the maximal levels of bgp, mgp and
grp expression indicating a correlation between development of the skeleton and
the expression of VKDP genes. These data are important for evaluating A. persicus
larval quality, understanding the influence of rearing biotic and abiotic factors
on skeletogenesis and recognizing the occurrence of skeletal deformities in this
species.
PMID- 29349780
TI - Protective Effect of BLED-exposed Conditioned Media on Cell Injury.
AB - Previous studies have reported that 450 nm blue light emitting diode (BLED)
induces apoptosis through a mitochondria-mediated pathway in cancer cells and
reduces the early stage tumor growth. This study was performed to determine the
effects of BLED-irradiated cell metabolites on cell injury. Our results showed
that conditioned medium (CM) from cells irradiated with low-dose BLED (LCM)
inhibited apoptosis and increased cell survival. Cell protection-related proteins
were identified in cell metabolites of CM and LCM using 2-DE and MALDI-TOF
analysis. Treatment with LCM inhibited apoptotic cell death and increased the
live cell population. The cellular protective effect of LCM was associated with
keratin and collagen type VI secretion from cells after low dose of BLED
irradiation. Interestingly, expression of endoplasmic reticulum stress proteins
was dose dependently increased after 4 h BLED irradiation. Only levels of BiP,
CHOP and ERO1-Lalpha were decreased significantly after 24 h incubation,
indicating their anti-apoptotic property in these cells. These results indicated
that cell metabolites stimulated by low-dose BLED irradiation have a
cytoprotective effect on cell injury via increasing transient intracellular ER
stress. Further studies remain to provide the molecular mechanisms of LCM for
cytoprotective activity.
PMID- 29349781
TI - Mirror neurons and intention understanding: Dissociating the contribution of
object type and intention to mirror responses using electromyography.
AB - Since their discovery in the monkey and human brain, mirror neurons have been
claimed to play a key role in understanding others' intentions. For example,
"action-constrained" mirror neurons in inferior parietal lobule fire when the
monkey observes a grasping movement that is followed by an eating action, but not
when it is followed by a placing action. It is claimed these responses enable the
monkey to predict the intentions of the actor. These findings have been
replicated in human observers by recording electromyography responses of the
mouth-opening mylohyoid muscle during action observation. Mylohyoid muscle
activity was greater during the observation of actions performed with the
intention to eat than of actions performed with the intention to place, again
suggesting an ability to predict the actor's intentions. However, in previous
studies, intention was confounded with object type (food for eating actions,
nonfood for placing actions). We therefore used electromyography to measure
mylohyoid activity in participants observing eating and placing actions. Unlike
previous studies, we used a design in which each object (food, nonfood) could be
both eaten and placed, and thus participants could not predict the actor's
intention at the onset of the action. Greater mylohyoid activity was found for
the observation of actions performed on food objects, irrespective of intention,
indicating that the object type, not the actor's intention, drives the mirror
response. This result suggests that observers' motor responses during action
observation reflect the presence of a particular object, rather than the actor's
underlying intentions.
PMID- 29349782
TI - New species of the genus Spectracanthicus (Loricariidae, Hypostominae,
Ancistrini) from the Rio Javaes (Rio Araguaia basin), with a description of gross
brain morphology.
AB - A new species of Spectracanthicus is described from the Rio Javaes, Rio Araguaia
basin. The new species is distinguished from its congeners (except
Spectracanthicus immaculatus) by colour pattern: body dark grey to dark brown
without dots or blotches (v. body colour with yellowish small dots in
Spectracanthicus murinus, Spectracanthicus punctatissimus and Spectracanthicus
tocantinensis and large white dots in Spectracanthicus zuanoni). It can be
further distinguished from S. immaculatus by having thicker and less numerous
teeth, with up to eight premaxillary and 20 dentary teeth (v. teeth thinner and
more numerous with up to 22 premaxillary and 30 dentary teeth); dorsal and caudal
fins without curved spines (v. dorsal and caudal fins with curved spines). Other
osteological characters can also diagnose the new species from its congeners. In
addition, a gross brain description and brief comments on the new species'
ecological habitat are given.
PMID- 29349783
TI - Development of Cotton Fabrics with Durable UV Protective and Self-cleaning
Property by Deposition of Low TiO2 Levels through Sol-gel Process.
AB - In this article, the deposition of TiO2 on cotton fabric using sol-gel technique
has been described. Various process routes (pad-dry-cure, pad-dry-hydrothermal
and pad-dry-solvothermal) were examined to impart a stable coating of TiO2 on
fabric. The role of precursor concentration, process temperature and time of
treatment were studied to aim at a wash durable, UV protective and self-cleaning
property in the treated fabric. EDX and ICP-MS techniques were used to examine
the add-on percentage of TiO2 on cotton fabrics treated via different routes. It
has been found that the TiO2 remains largely amorphous and nondurable if it is
given a short thermal treatment. To convert the deposited TiO2 to its anatase
crystal form, a prolonged hydrothermal treatment for at least 3 h needs to be
given. TiO2 deposition levels of less than 0.1% were found to be effective in
imparting reasonable degree of UV protection and self-cleaning property to the
cotton fabric. The self-cleaning ability of the treated fabric against coffee
stain was also studied and was found to be related to the process route and the
deposition levels of TiO2 .
PMID- 29349784
TI - Magnetic molecularly imprinted polymers based on silica modified by deep eutectic
solvents for the rapid simultaneous magnetic-based solid-phase extraction of
Salvia miltiorrhiza bunge, Glycine max (Linn.) Merr and green tea.
AB - Novel magnetic molecularly imprinted polymers (MMIPs) with multiple-template
based on silica were modified by four types of deep eutectic solvents (DESs) for
the rapid simultaneous magnetic solid-phase extraction (MSPE) of tanshinone I,
tanshinone IIA, and cryptotanshinone from Salvia miltiorrhiza bunge; glycitein,
genistein, and daidzein from Glycine max (Linn.) Merr; and epicatechin,
epigallocatechin gallate, and epicatechin gallate from green tea, respectively.
The synthesized materials were characterized by Fourier transform infrared
spectroscopy and field emission scanning electron microscopy. Single factor
experiments were to explore the relationship between the extraction efficiency
and four factors (the sample solution pH, amount of DESs for modification, amount
of adsorbent, and extraction time). It was showed that the DES4-MMIPs have better
extraction ability than the MMIPs without DESs and the other three DESs-modified
MMIPs. The best extraction recoveries with DES4-MMIP were tanshinone I (85.57%),
tanshinone IIA (80.58%), cryptotanshinone (92.12%), glycitein (81.65%), genistein
(87.72%), daidzein (92.24%), epicatechin (86.43%), epigallocatechin gallate
(80.92%), and epicatechin gallate (93.64%), respectively. The novel multiple
template MMIPs materials modified by DES for the rapid simultaneous MSPE of
active compounds were proved to reduce the experimental steps than single
template technique, and increase the extraction efficiency.
PMID- 29349785
TI - A novel MLPH variant in dogs with coat colour dilution.
AB - Coat colour dilution may be the result of altered melanosome transport in
melanocytes. Loss-of-function variants in the melanophilin gene (MLPH) cause a
recessively inherited form of coat colour dilution in many mammalian and avian
species including the dog. MLPH corresponds to the D locus in many domestic
animals, and recessive alleles at this locus are frequently denoted with d. In
this study, we investigated dilute coloured Chow Chows whose coat colour could
not be explained by their genotype at the previously known MLPH:c.-22G>A variant.
Whole genome sequencing of such a dilute Chow Chow revealed another variant in
the MLPH gene: MLPH:c.705G>C. We propose to designate the corresponding mutant
alleles at these two variants d1 and d2 . We performed an association study in a
cohort of 15 dilute and 28 non-dilute Chow Chows. The dilute dogs were all either
compound heterozygous d1 /d2 or homozygous d2 /d2 , whereas the non-dilute dogs
carried at least one wildtype allele D. The d2 allele did not occur in 417 dogs
from diverse other breeds. However, when we genotyped a Sloughi family, in which
a dilute coloured puppy had been born out of non-dilute parents, we again
observed perfect co-segregation of the newly discovered d2 allele with coat
colour dilution. Finally, we identified a blue Thai Ridgeback with the d1 /d2
genotype. Thus, our data identify the MLPH:c.705G>C as a variant explaining a
second canine dilution allele. Although relatively rare overall, this d2 allele
is segregating in at least three dog breeds, Chow Chows, Sloughis and Thai
Ridgebacks.
PMID- 29349786
TI - Acute lion's mane jellyfish, Cyanea capillata (Cnideria: Scyphozoa), exposure to
Atlantic salmon (Salmo salar L.).
AB - Jellyfish-induced gill pathology relies upon occasional diagnostic observations
yet the extent and impact of jellyfish blooms on aquaculture may be significant.
Idiopathic gill lesions are often observed in apparently healthy fish. This study
exposed Atlantic salmon (Salmo salar L.) smolts to macerated Cyanea capillata at
2.5 and 5 g/L for 2 hr under controlled laboratory conditions. Blood chemistry
and gill histopathology were examined over a subsequent 4-week period. Fish
showed an acute response to the presence of jellyfish, including characteristic
external "whiplash" discoloration of the skin and acute increases in blood
electrolytes and CO2 concentration; however, these were resolved within 4 days
after exposure. Histopathologically, gills showed first an acute oedema with
epithelial separation followed by focal haemorrhage and thrombus formation, and
then progressive inflammatory epithelial hyperplasia that progressively resolved
over the 4 weeks post-exposure. Results were consistent with the envenomation of
gills with cytotoxic neurotoxins and haemolysins known to be produced by C.
capillata. This study suggests that many focal hyperplastic lesions on gills,
especially those involving focal thrombi, may be the result of jellyfish stings.
Thus, the presence of jellyfish and their impact may be severe and understated in
terms of marine fish aquaculture and fish welfare.
PMID- 29349787
TI - Treatment of lumpfish (Cyclopterus lumpus L.) infected with Gyrodactylus
cyclopteri (Scyborskaya 1948).
PMID- 29349788
TI - Roles of water quality and disinfectant application on inactivation of fish
pathogenic Streptococcus agalactiae with povidone iodine, quaternary ammonium
compounds and glutaraldehyde.
AB - Streptococcosis is an important bacterial disease in Nile tilapia causing severe
economic losses to tilapia aquaculture worldwide. The effects of water quality
(low- [LS] and high-level [HS] soiling, to mimic clean or dirty surface
conditions and temperatures) and disinfectant application (diluted concentrations
and exposure time) were characterized on the inactivation of Streptococcus
agalactiae isolated from diseased tilapia. Five isolates were tested against
three commercial disinfectant products with the main ingredients being povidone
iodine (Anidine 100TM; AD), benzalkonium chloride (Better BKC 80%TM; BKC 80), and
a mixture of quaternary ammonium compounds and glutaraldehyde (ChloraldehydeTM;
CR). CR demonstrated highest efficacy to S. agalactiae inactivation, followed by
BKC 80 and AD, respectively. Higher-level soiling, low temperature, diluted
concentrations and short exposure time all decreased the disinfectant efficacy.
CR and BKC 80 provided more than 5-log inactivation at 1-min exposure at 20
degrees C under HS conditions, and also with ten-fold-diluted concentrations at
60-min exposure time at 30 degrees C. However, AD required 10-min exposure to
effectively remove bacteria under LS conditions at 30 degrees C. The results
could facilitate aquaculture management planning that leads to operating cost
reductions and improvements in biosecurity.
PMID- 29349789
TI - Postmarketing cases of eluxadoline-associated pancreatitis in patients with or
without a gallbladder.
AB - BACKGROUND: Cases of pancreatitis were identified in the eluxadoline clinical
development program, reflected in initial product labelling, and the subject of
postmarketing reports. AIM: To analyse postmarketing cases of eluxadoline
associated pancreatitis. METHODS: We retrospectively analysed all US adverse
event reports of pancreatitis associated with eluxadoline reported to the FDA
Adverse Event Reporting System (FAERS) database from May 27, 2015 through
February 15, 2017. RESULTS: The analysis included 119 cases of pancreatitis
associated with eluxadoline; one resulted in death and 75 in hospitalisation.
Sixty-seven cases reported the presence (n = 12) or absence (n = 55) of the
patient's gallbladder. The eluxadoline dose received in the 55 cases of patients
without gallbladders was 75 mg (n = 43), 100 mg (n = 5), or not reported (n = 7).
Of the 119 cases, 37 reported the patient did not abuse alcohol and 82 did not
report the alcohol abuse status. The single fatal case occurred in a patient
without a gallbladder who received eluxadoline 75 mg and did not abuse alcohol.
Forty-seven cases reported development of pancreatitis within the first or second
dose of eluxadoline initiation. The median time to onset for the development of
pancreatitis (n = 83) was 1 day, ranging from 1 to 56 days of continued use of
eluxadoline. CONCLUSION: The FAERS cases suggest that patients with or without a
gallbladder receiving eluxadoline are at risk for the development of
pancreatitis. However, patients without a gallbladder, despite receiving the
recommended lower dose of eluxadoline 75 mg and screening for alcohol abuse,
appear to be overrepresented among patients who developed eluxadoline-associated
pancreatitis.
PMID- 29349790
TI - Identification of the absorbed components and metabolites of modified Huo Luo
Xiao Ling Dan in rat plasma by UHPLC-Q-TOF/MS/MS.
AB - To reveal the material basis of Huo Luo Xiao Ling Dan (HLXLD), a sensitive and
selective ultra-high performance liquid chromatography coupled with quadrupole
time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) method was developed to
identify the absorbed components and metabolites in rat plasma after oral
administration of HLXLD. The plasma samples were pretreated by liquid-liquid
extraction and separated on a Shim-pack XR-ODS C18 column (75 * 3.0 mm, 2.2 MUm)
using a gradient elution program. With the optimized conditions and single sample
injection of each positive or negative ion mode, a total of 109 compounds,
including 78 prototype compounds and 31 metabolites, were identified or
tentatively characterized. The fragmentation patterns of representative compounds
were illustrated as well. The results indicated that aromatization and hydration
were the main metabolic pathways of lactones and tanshinone-related metabolites;
demethylation and oxidation were the major metabolic pathways of alkaloid-related
compounds; methylation and sulfation were the main metabolic pathways of phenolic
acid-related metabolites. It is concluded the developed UHPLC-Q-TOF/MS method
with high sensitivity and resolution is suitable for identifying and
characterizing the absorbed components and metabolites of HLXLD, and the results
will provide essential data for further studying the relationship between the
chemical components and pharmacological activity of HLXLD.
PMID- 29349791
TI - Predicting patterns of change and stability in student performance across a
medical degree.
AB - CONTEXT: Evidence of predictive validity is essential for making robust selection
decisions in high-stakes contexts such as medical student selection. Currently
available evidence is limited to the prediction of academic performance at single
points in time with little understanding of the factors that might undermine the
predictive validity of tests of academic and non-academic qualities considered
important for success. This study addressed these issues by predicting students'
changing performance across a medical degree and assessing whether factors
outside an institution's control (such as the uptake of commercial coaching)
impact validity. METHODS: Three cohorts of students (n = 301) enrolled in an
undergraduate medical degree from 2007-2013 were used to identify trajectories of
student academic performance using growth mixture modelling. Multinomial logistic
regression assessed whether past academic performance, a test of cognitive
ability and a multiple mini-interview could predict a student's likely trajectory
and whether this predictive validity was different for those who undertook
commercial coaching compared with those who didn't. RESULTS: Among the medical
students who successfully graduated (n = 268), four unique trajectories of
academic performance were identified. In three trajectories, performance changed
at the time when learning became more self-directed and focused on clinical
specialties. Scores on all selection tests, with the exception of a test of
abstract reasoning, significantly affected the odds of following a trajectory
that was consistently below average. However, selection tests could not
distinguish those whose performance improved across time from those whose
performance declined after an average start. Commercial coaching increased the
odds of being among the below-average performers, but did not alter the
predictive validity of the selection tests. CONCLUSION: Identifying distinct
groups of students has important implications for selection, but also for
educating medical students. Commercial coaching may result in selecting students
who are less suited for coping with the rigours of medical studies.
PMID- 29349792
TI - Meta-analysis of Gaussian individual patient data: Two-stage or not two-stage?
AB - Quantitative evidence synthesis through meta-analysis is central to evidence
based medicine. For well-documented reasons, the meta-analysis of individual
patient data is held in higher regard than aggregate data. With access to
individual patient data, the analysis is not restricted to a "two-stage" approach
(combining estimates and standard errors) but can estimate parameters of interest
by fitting a single model to all of the data, a so-called "one-stage" analysis.
There has been debate about the merits of one- and two-stage analysis. Arguments
for one-stage analysis have typically noted that a wider range of models can be
fitted and overall estimates may be more precise. The two-stage side has
emphasised that the models that can be fitted in two stages are sufficient to
answer the relevant questions, with less scope for mistakes because there are
fewer modelling choices to be made in the two-stage approach. For Gaussian data,
we consider the statistical arguments for flexibility and precision in small
sample settings. Regarding flexibility, several of the models that can be fitted
only in one stage may not be of serious interest to most meta-analysis
practitioners. Regarding precision, we consider fixed- and random-effects meta
analysis and see that, for a model making certain assumptions, the number of
stages used to fit this model is irrelevant; the precision will be approximately
equal. Meta-analysts should choose modelling assumptions carefully. Sometimes
relevant models can only be fitted in one stage. Otherwise, meta-analysts are
free to use whichever procedure is most convenient to fit the identified model.
PMID- 29349793
TI - The effectiveness and safety of ledipasvir plus sofosbuvir in adolescents with
chronic hepatitis C virus genotype 4 infection: a real-world experience.
AB - BACKGROUND: The combination of ledipasvir plus sofosbuvir was recently approved
for treatment of adolescent (12-17 years) HCV genotype 1, 4, 5 & 6 patients.
However, few clinical trials have been performed in genotype 1 patients. AIM: To
investigate the effectiveness and safety of ledipasvir plus sofosbuvir in chronic
HCV adolescent patients with genotype 4 in the real world. METHODS: This
prospective multicentre (six centres) open-label study included 144 adolescent
chronic HCV patients with genotype 4 (mean age 14 +/- 2, 69% males). All patients
received a combination tablet containing 400 mg sofosbuvir and 90 mg ledipasvir
once daily for 12 weeks. Laboratory and virological markers were evaluated at
baseline, week 4, week 8 and week 12 (EOT), and 12 weeks after end of treatment
(SVR12). RESULTS: SVR12 was observed in 142/144 patients (99%). The relapsers
occurred in previous naive patients (n = 2/128, 2%), while the experienced
patients showed 100% SVR12. SVR12 was 98% in F0/F1 patients in comparison to 100%
in F2 patients (P = 0.552). No serious side effects were observed, nor was
treatment discontinuation or death. Headache was the most common side effect in
all patients (20%). In experienced patients, pruritus (31%, P = 0.007), diarrhoea
(44%, P < 0.001) and skin rash (19%, P = 0.002) were higher than in naive
patients. CONCLUSIONS: A ledipasvir plus sofosbuvir regimen is well tolerated and
effective, and can be used safely in treating adolescent patients with chronic
hepatitis C genotype 4.
PMID- 29349794
TI - Adolescents' Reward-related Neural Activation: Links to Thoughts of Nonsuicidal
Self-Injury.
AB - Adolescence is a critical developmental period marked by an increase in risk
behaviors, including nonsuicidal self-injury (NSSI). Heightened reward-related
brain activation and relatively limited recruitment of prefrontal regions
contribute to the initiation of risky behaviors in adolescence. However, neural
reward processing has not been examined among adolescents who are at risk for
future engagement for NSSI specifically, but who have yet to actually engage in
this behavior. In the current fMRI study (N = 71), we hypothesized that altered
reward processing would be associated with adolescents' thoughts of NSSI. Results
showed that NSSI youth exhibited heightened activation in the bilateral putamen
in response to a monetary reward. This pattern of findings suggests that
heightened neural sensitivity to reward is associated with thoughts of NSSI in
early adolescence. Implications for prevention are discussed.
PMID- 29349795
TI - Quality of life assumptions determine which cervical cancer screening strategies
are cost-effective.
AB - Quality-adjusted life years are used in cost-effectiveness analyses (CEAs). To
calculate QALYs, a "utility" (0-1) is used for each health state induced or
prevented by the intervention. We aimed to estimate the impact of quality of life
(QoL) assumptions (utilities and durations of health states) on CEAs of cervical
cancer screening. To do so, 12 alternative sets of utility assumptions were
retrieved from published cervical cancer screening CEAs. Two additional sets were
based on empirical QoL data that were integrally obtained through two different
measures (SF-6D and EQ-5D) from eight groups of women (total n = 3,087), from
invitation for screening to diagnosis with cervical cancer. Per utility set we
calculated the number of quality-adjusted days lost (QADL) for each relevant
health state in cervical cancer screening, by multiplying the study-specific
assumed disutilities (i.e., 1-utility) with study-specific durations of the loss
in QoL, resulting in 14 "QADL-sets." With microsimulation model MISCAN we
calculated cost-effectiveness of 342 alternative screening programs (varying in
primary screening test [Human Papillomavirus (HPV) vs. cytology], starting ages,
and screening interval) for each of the 14 QADL-sets. Utilities used in CEAs
appeared to differ largely. We found that ten QADL-sets from the literature
resulted in HPV and two in cytology as preferred primary test. The SF-6D
empirical QADL-set resulted in cytology and the EQ-5D one in HPV as preferred
primary test. In conclusion, assumed utilities and health state durations
determine cost-effectiveness of cervical cancer screening. Also, the measure used
to empirically assess utilities can be crucial for CEA conclusions.
PMID- 29349796
TI - Quantification of acyclovir in dermal interstitial fluid and human serum by ultra
high-performance liquid-high-resolution tandem mass spectrometry for topical
bioequivalence evaluation.
AB - Time-concentration curves for the topical anti-viral drug acyclovir can provide
valuable information for drug development. Open flow microperfusion is used for
continuous sampling of dermal interstitial fluid but it requires validated
methods for subsequent sample analysis. Therefore, we developed a sensitive,
selective and high-throughput ultra-high-performance liquid chromatography-high
resolution tandem mass spectrometry method to determine acyclovir in human dermal
interstitial fluid and serum. We validated the method over a concentration range
of 0.1-25 ng/mL for a sample volume of just 20 MUL and employed cation-exchange
solid-phase extraction in a fully automated sample treatment procedure. Short-
and long-term sample stability data and the analysis of 5000 samples from a
clinical trial demonstrate the successful application of our method.
PMID- 29349797
TI - Efficacy and toxicity of praziquantel in helminth-infected barbel (Barbus barbus
L.).
AB - This study evaluated efficacy and toxicity of the pyrazinoisoquinoline
anthelmintic praziquantel (PZQ) in barbel infected with metacercariae of
Diplostomum spathaceum and adult Pomphorhynchus laevis, and assessed antioxidant
biomarkers and the lipid peroxidation response in juvenile barbel post-treatment.
The estimated 96-hr LC50 of PZQ was 28.6 mg/L. For evaluation of efficacy, barbel
naturally infected with D. spathaceum were exposed to a 10 and 20 mg/L PZQ 4-day
bath treatment. Both concentrations were 100% effective against D. spathaceum and
significantly (p < .01) affected the activity of catalase, superoxide dismutase,
glutathione reductase and glutathione-S-transferase as well as levels of reduced
glutathione in liver and muscle. The efficacy of orally administered PZQ was
assessed in adult barbel naturally infected with P. laevis. Fish were
administered 10, 30 and 50 mg/kg of body weight and examined via gut dissection
after 6 days. The 50 mg/kg dose significantly decreased the intensity of
infection. Praziquantel is a feasible bath treatment for barbel infected with D.
spathaceum and has potential for oral treatment of broodfish infected with P.
laevis.
PMID- 29349798
TI - Small area estimation of proportions with different levels of auxiliary data.
AB - Binary data are often of interest in many small areas of applications. The use of
standard small area estimation methods based on linear mixed models becomes
problematic for such data. An empirical plug-in predictor (EPP) under a unit
level generalized linear mixed model with logit link function is often used for
the estimation of a small area proportion. However, this EPP requires the
availability of unit-level population information for auxiliary data that may not
be always accessible. As a consequence, in many practical situations, this EPP
approach cannot be applied. Based on the level of auxiliary information
available, different small area predictors for estimation of proportions are
proposed. Analytic and bootstrap approaches to estimating the mean squared error
of the proposed small area predictors are also developed. Monte Carlo simulations
based on both simulated and real data show that the proposed small area
predictors work well for generating the small area estimates of proportions and
represent a practical alternative to the above approach. The developed predictor
is applied to generate estimates of the proportions of indebted farm households
at district-level using debt investment survey data from India.
PMID- 29349799
TI - Simultaneous LC-MS/MS bioanalysis of etoposide and paclitaxel in mouse tissues
and plasma after oral administration of self-microemulsifying drug-delivery
systems.
AB - In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method
was developed and validated to simultaneously determine the anticancer drugs
etoposide and paclitaxel in mouse plasma and tissues including liver, kidney,
lung, heart, spleen and brain. The analytes were extracted from the matrices of
interest by liquid-liquid extraction using methyl tert-butyl ether
dichloromethane (1:1, v/v). Chromatographic separation was achieved on an
Ultimate XB-C18 column (100 * 2.1 mm, 3 MUm) at 40 degrees C and the total run
time was 4 min under a gradient elution. Ionization was conducted using
electrospray ionization in the positive mode. Stable isotope etoposide-d3 and
docetaxel were used as the internal standards. The lower limit of quantitation
(LLOQ) of etoposide was 1 ng/g tissue for all tissues and 0.5 ng/mL for plasma.
The LLOQ of paclitaxel was 0.4 ng/g tissue and 0.2 ng/mL for all tissues and
plasma, respectively. The coefficients of correlation for all of the analytes in
the tissues and plasma were >0.99. Both intra- and inter-day accuracy and
precision were satisfactory. This method was successfully applied to measure
plasma and tissue drug concentrations in mice treated with etoposide and
paclitaxel-loaded self-microemulsifying drug-delivery systems.
PMID- 29349800
TI - Specific cutaneous infiltrates of acute myeloid leukaemia in a venous leg ulcer:
an unusual presentation of leukaemia cutis.
PMID- 29349801
TI - Evaluating the effects of rater and subject factors on measures of association.
AB - Large-scale agreement studies are becoming increasingly common in medical
settings to gain better insight into discrepancies often observed between
experts' classifications. Ordered categorical scales are routinely used to
classify subjects' disease and health conditions. Summary measures such as
Cohen's weighted kappa are popular approaches for reporting levels of association
for pairs of raters' ordinal classifications. However, in large-scale studies
with many raters, assessing levels of association can be challenging due to
dependencies between many raters each grading the same sample of subjects'
results and the ordinal nature of the ratings. Further complexities arise when
the focus of a study is to examine the impact of rater and subject
characteristics on levels of association. In this paper, we describe a flexible
approach based upon the class of generalized linear mixed models to assess the
influence of rater and subject factors on association between many raters'
ordinal classifications. We propose novel model-based measures for large-scale
studies to provide simple summaries of association similar to Cohen's weighted
kappa while avoiding prevalence and marginal distribution issues that Cohen's
weighted kappa is susceptible to. The proposed summary measures can be used to
compare association between subgroups of subjects or raters. We demonstrate the
use of hypothesis tests to formally determine if rater and subject factors have a
significant influence on association, and describe approaches for evaluating the
goodness-of-fit of the proposed model. The performance of the proposed approach
is explored through extensive simulation studies and is applied to a recent large
scale cancer breast cancer screening study.
PMID- 29349802
TI - Shades of Awareness on the Mechanisms Underlying the Quality of Conscious
Representations: A Commentary to Fazekas and Overgaard ().
AB - Fazekas and Overgaard () present a novel, multidimensional model that explains
different ways in which conscious representations can be degraded. Moreover, the
authors discuss possible mechanisms that underlie different kinds of degradation,
primarily those related to attentional processing. In this letter, we argue that
the proposed mechanisms are not sufficient. We propose that (1) attentional
mechanisms work differently at various processing stages; and (2) factors that
are independent of attentional ones, such as expectation, previous experience,
and context, should be accounted for if we are aiming to construct a
comprehensive model of conscious visual perception.
PMID- 29349803
TI - Assessment of mitral annulus and mitral leaflet in nonvalvular atrial
fibrillation patients with various degrees of mitral regurgitation: Real time 3D
transesophageal echocardiography.
AB - AIM: To study the changes of mitral valve (MV) in patients with nonvalvular
atrial fibrillation (NVAF)-related mitral regurgitation (MR) and the relationship
between MV parameters and the enlarged left atrium (LA). MATERIALS AND METHODS: A
total of 43 patients with NVAF were divided into two groups: (1) the MR1 group
with mild MR and (2) the MR2 group with moderate-to-severe MR. Real time 3D
transesophageal echocardiography (TEE) was performed to detect the structure of
MV. RESULTS: There were no significant differences in the basic characteristics
among the three groups. As compared with the control group, anterolateral to
posteromedial diameter of the annulus (DALPm), anterior to posterior diameter
(DAP), three-dimensional circumference (C3D), two-dimensional area (A2D), three
dimensional area (A3D), exposed area of the leaflets (A3DE), and NPA (nonplanar
angle) were significantly increased, whereas height and ellipticity were
significantly decreased in the MR1 group and MR2 group. The overall longitudinal
strain of left atrium (GLS) was significantly decreased in the MR1 and MR2 groups
compared to the control group. Furthermore, GLS was inversely correlated with
DALPm, DAP, C3D, A2D, A3D, A3DE, and NPA, whereas positively correlated with
height, ellipticity, and the leaflet tenting height in both MR1 and MR2 groups.
CONCLUSION: Even in NVAF patients with mild MR, the structure of MV was changed
intensively with the expansion and deformation of the "saddle shape" structure.
The deformation of MV was associated with the decreased function of LA. Our
results may provide novel insight into evaluation risk factors leading to AF
recurrence after ablation procedures.
PMID- 29349804
TI - Integrity situational judgement test for medical school selection: judging 'what
to do' versus 'what not to do'.
AB - CONTEXT: Despite their widespread use in medical school selection, there remains
a lack of clarity on exactly what situational judgement tests (SJTs) measure.
OBJECTIVES: We aimed to develop an SJT that measures integrity by combining
critical incident interviews (inductive approach) with an innovative deductive
approach. The deductive approach guided the development of the SJT according to
two established theoretical models, of which one was positively related to
integrity (honesty-humility [HH]) and one was negatively related to integrity
(cognitive distortions [CD]). The Integrity SJT covered desirable (HH-based) and
undesirable (CD-based) response options. We examined the convergent and
discriminant validity of the Integrity SJT and compared the validity of the HH
based and CD-based subscores. METHODS: The Integrity SJT was administered to 402
prospective applicants at a Dutch medical school. The Integrity SJT consisted of
57 scenarios, each followed by four response options, of which two represented HH
facets and two represented CD categories. Three SJT scores were computed,
including a total, an HH-based and a CD-based score. The validity of these scores
was examined according to their relationships with external integrity-related
measures (convergent validity) and self-efficacy (discriminant validity).
RESULTS: The three SJT scores correlated significantly with all integrity-related
measures and not with self-efficacy, indicating convergent and discriminant
validity. In addition, the CD-based SJT score correlated significantly more
strongly than the HH-based SJT score with two of the four integrity-related
measures. CONCLUSIONS: An SJT that assesses the ability to correctly recognise CD
based response options as inappropriate (i.e. what one should not do) seems to
have stronger convergent validity than an SJT that assesses the ability to
correctly recognise HH-based response options as appropriate (i.e. what one
should do). This finding might be explained by the larger consensus on what is
considered inappropriate than on what is considered appropriate in a challenging
situation. It may be promising to focus an SJT on the ability to recognise what
one should not do.
PMID- 29349805
TI - Hybrid Continuous-Flow Total Artificial Heart.
AB - Clinical studies using total artificial hearts (TAHs) have demonstrated that
pediatric and adult patients derive quality-of-life benefits from this form of
therapy. Two clinically-approved TAHs and other pumps under development, however,
have design challenges and limitations, including thromboembolic events,
neurologic impairment, infection risk due to large size and percutaneous
drivelines, and lack of ambulation, to name a few. To address these limitations,
we are developing a hybrid-design, continuous-flow, implantable or
extracorporeal, magnetically-levitated TAH for pediatric and adult patients with
heart failure. This TAH has only two moving parts: an axial impeller for the
pulmonary circulation and a centrifugal impeller for the systemic circulation.
This device will utilize the latest generation of magnetic bearing technology.
Initial geometries were established using pump design equations, and
computational modeling provided insight into pump performance. The designs were
the basis for prototype manufacturing and hydraulic testing. The study results
demonstrate that the TAH is capable of delivering target blood flow rates of 1
6.5 L/min with pressure rises of 1-92 mm Hg for the pulmonary circulation and 24
150 mm Hg for the systemic circulation at 1500-10 000 rpm. This initial design of
the TAH was successful and serves as the foundation to continue its development
as a novel, more compact, nonthrombogenic, and effective therapeutic alternative
for infants, children, adolescents, and adults with heart failure.
PMID- 29349806
TI - Blue Monday Is Real for Suicide: A Case-Control Study of 188,601 Suicides.
AB - Many studies have reported that suicides tend to occur on Mondays. However, owing
to a lack of controls, conclusive findings on the potential effects of a day of
the week on suicides have been lacking. We analyzed public data for causes of
death from 1997 to 2015 in the Republic of Korea. Accidental death was used as a
control group. The probability of suicide on each day of the week according to
age group was calculated. A total of 377,204 deaths (188,601 suicides and 188,603
accidental deaths) were used. The frequency of suicide was highest on Monday and
decreased throughout the week until Saturday. Accidental death was highest on
Saturday and showed no variations according to weekday. For people in their teens
and 20s, the probabilities of suicide on Monday were 9% and 10% higher,
respectively, than those on Sunday. As age increased, the differences in suicide
probability according to the day of the week were attenuated. The so-called Blue
Monday effect is real, particularly for people in their teens and 20s. Suicide
prevention strategies that aim to attenuate the burden and stress of Mondays
should be planned.
PMID- 29349807
TI - Possible role of plasmacytoid dendritic cells in pityriasis lichenoides.
AB - BACKGROUND: Plasmacytoid dendritic cells (pDCs) and their product, type I
interferons (IFNs), have been implicated in the pathogenesis of several skin
disorders characterized by an interface dermatitis (ID) pattern, such as lichen
planus (LP). A type I IFN signature has previously been documented in pityriasis
lichenoides (PL). Although pDCs are known to be the main source and most potent
producers of local type I IFNs, their role in PL has not been investigated. AIM:
To investigate the role of pDCs in PL. METHODS: In total, 20 cases of PL and 20
comparable cases of LP were immunohistochemically tested for pDC occurrence and
type I IFN production using anti-blood-derived dendritic cell antigen-2 (BDCA2; a
specific pDC marker) and anti-myxovirus protein A (anti-MxA) antibodies (indirect
marker of pDC activity), respectively. MxA is a well-established surrogate marker
for local type 1 IFN production. A semiquantitative scoring system was used.
RESULTS: pDCs were present in all 40 cases with no statistically significant
difference between the two groups. MxA expression was intense and diffuse in the
majority of PL and LP cases. CONCLUSIONS: pDCs constitute a central component of
the inflammatory infiltrate in PL, suggesting that PL shares with the other
entities that exhibit an ID a common pDC-driven process through type I IFN
production, which ultimately leads to the cytotoxic attack.
PMID- 29349808
TI - Promises and pitfalls in the development of biomarkers that can promote early
intervention in children at risk.
AB - The cost to individuals and to society of psychopathology that emerges in
childhood is substantial. Children whose problems are undiagnosed or inadequately
treated struggle in school, experience rejection by peers, and become a source of
stress for caregivers and teachers. As adults, their mental health problems tend
to recur and their cognitive difficulties persist. Clinicians hold a well-founded
belief that early identification of children who are at risk for psychopathology
is the key to prevention.
PMID- 29349809
TI - Alexithymia as a potential source of symptom over-reporting: An exploratory study
in forensic patients and non-forensic participants.
AB - The traditional interpretation of symptom over-reporting is that it indicates
malingering. We explored a different perspective, namely that over-reporting of
eccentric symptoms is related to deficits in articulating internal experiences
(i.e., alexithymia). Given that alexithymia has been linked to sleep problems and
that fatigue may fuel inattentive responding to symptom lists, we administered
measures of alexithymia (TAS-20) and symptom over-reporting (SIMS), but also
sleep quality (SLEEP-50) to forensic psychiatric outpatients (n = 40) and non
forensic participants (n = 40). Forensic patients scored significantly higher on
all three indices than non-forensic participants. In the total sample as well as
in subsamples, over-reporting correlated positively and significantly with
alexithymia, with rs being in the 0.50-0.65 range. Sleep problems were also
related to over-reporting, but in the full sample and in the forensic subsample,
alexithymia predicted variance in over-reporting over and above sleep problems.
Although our study is cross-sectional in nature, its results indicate that
alexithymia as a potential source of over-reporting merits systematic research.
PMID- 29349810
TI - Medicago truncatula copper transporter 1 (MtCOPT1) delivers copper for symbiotic
nitrogen fixation.
AB - Copper is an essential nutrient for symbiotic nitrogen fixation. This element is
delivered by the host plant to the nodule, where membrane copper (Cu) transporter
would introduce it into the cell to synthesize cupro-proteins. COPT family
members in the model legume Medicago truncatula were identified and their
expression determined. Yeast complementation assays, confocal microscopy and
phenotypical characterization of a Tnt1 insertional mutant line were carried out
in the nodule-specific M. truncatula COPT family member. Medicago truncatula
genome encodes eight COPT transporters. MtCOPT1 (Medtr4g019870) is the only
nodule-specific COPT gene. It is located in the plasma membrane of the
differentiation, interzone and early fixation zones. Loss of MtCOPT1 function
results in a Cu-mitigated reduction of biomass production when the plant obtains
its nitrogen exclusively from symbiotic nitrogen fixation. Mutation of MtCOPT1
results in diminished nitrogenase activity in nodules, likely an indirect effect
from the loss of a Cu-dependent function, such as cytochrome oxidase activity in
copt1-1 bacteroids. These data are consistent with a model in which MtCOPT1
transports Cu from the apoplast into nodule cells to provide Cu for essential
metabolic processes associated with symbiotic nitrogen fixation.
PMID- 29349811
TI - Genetic analysis of interleukin 18 gene polymorphisms in alopecia areata.
AB - BACKGROUND: Alopecia areata (AA), which appears as nonscarring hair shedding on
any hair-bearing area, is a common organ-specific autoimmune condition. Cytokines
have important roles in the development of AA. Interleukin (IL) 18 is a
significant proinflammatory cytokine that was found higher in the patients with
AA. We aimed to investigate whether the IL-18 (rs187238 and rs1946518) single
nucleotide polymorphisms (SNPs) may be associated with AA and/or clinical outcome
of patients with AA in Turkish population. METHODS: Genotyping of rs187238 and
rs1946518 SNPs were detected using sequence-specific primer-polymerase chain
reaction (SSP-PCR) method in 200 patients with AA and 200 control subjects.
RESULTS: The genotype distribution of rs1946518 (-607C>A) SNP was found to be
statistically significantly different among patients with AA and controls (P =
.0008). Distribution of CC+CA genotypes and frequency of -607/allele C of
rs1946518 SNP were higher in patients with AA (P = .001, P = .001, respectively).
The genotype distribution of rs187238 (-137G>C) SNP was found to be statistically
significantly different among patients with AA and control subjects (P = .0014).
Distribution of GG genotype and frequency of -137/allele G of rs187238 SNP were
higher in patients with AA (P = .0003, P = .001, respectively). CONCLUSION: The
rs1946518 (-607C>A) and rs187238 (-137G>C) polymorphisms were found associated
with alopecia areata disease. The study suggests that IL-18 rs187238 and
rs1946518 SNPs may be the cause of the AA susceptibility.
PMID- 29349812
TI - Drug promotion practices: A review.
AB - Over the years, the pharmaceutical industry has been at the forefront of research
and innovation in drug discovery and development. The process of drug discovery
extending from preclinical studies to multicentric clinical trials and
postmarketing phase is a costly affair running into billions of dollars. On the
flip side, not all investigational molecules clear the trial phases and get
approved, which puts pressure on the manufacturers to maximize the profit from
approved drugs. It is in this key area that the practice of drug promotion plays
its role. The World Health Organization defines drug promotion as "all
informational and persuasive activities by manufacturers and distributors, the
effect of which is to influence the prescription, supply, purchase or use of
medicinal drugs". With its humble intent of creating awareness among healthcare
professionals and updating their knowledge on recent advances in treatment
options, drug promotion has been an important tool, but gradually it has evolved
to embrace aggressive marketing strategies and sometimes unethical business and
scientific practices where the need for profit-making eclipses commitment to
patient care and scientific exploration. In this review, we discuss the evolution
of drug promotion practices, the various types, its merits and demerits, the
influence of drug promotion on physician prescribing behaviour, the role of
regulatory bodies, unethical promotional practices and finally summarize with
future directions.
PMID- 29349813
TI - HLA-B27 testing: A journey from flow cytometry to molecular subtyping.
AB - BACKGROUND: Determination of HLA-B27 status plays an important role as adjuvant
in suspected cases for diagnosis of Ankylosing Spondilytis (AS). Objectives of
this study were to evaluate (i) flow cytometry method in comparison with DNA
microarray for HLA-B27 typing and (ii) EUROArray HLA-B27 Direct assay for HLA-B27
allele detection along with discrimination of AS/non-AS subtypes in Indian
population. METHODS: A total of 7543 patients with a presumptive clinical
diagnosis of AS were referred for screening of HLA-B27. All samples were
initially tested by flow cytometry, and based on its findings, 1560 samples were
analyzed for the presence of HLA-B27 allele by microarray technology. A subset of
samples (n = 200) were further tested by DNA sequencing for identification of HLA
B27 subtypes. RESULTS: Screening of HLA-B27 by flow cytometry reported 1551
positive (20.56%) and 5556 negative (73.65%) cases. Remaining 436 (5.78%) samples
were identified within equivocal zone. Of cases (n = 1560) analyzed by microarray
method, 1333 (85.44%) and 227 (14.55%) were detected microarray positive and
negative, respectively. DNA sequencing identified HLA-B*27:07 as the predominant
subtype among cases showing ex2 positivity by microarray method. Of 200 cases, 20
cases (14 of HLA-B*07 and 6 of HLA-B*37) of HLA-B27 cross-reactive subtypes were
also identified. CONCLUSION: We recommend DNA typing as a complementary tool
along with flow cytometry to accomplish successful HLA-B27 phenotype
determination. This is the first study among Indian population to evaluate
efficacy of EUROArray to detect B27 allele and its potential to indicate the
presence of nondisease-associated alleles in Indian population.
PMID- 29349814
TI - VO2 /TiN Plasmonic Thermochromic Smart Coatings for Room-Temperature
Applications.
AB - Vanadium dioxide/titanium nitride (VO2 /TiN) smart coatings are prepared by
hybridizing thermochromic VO2 with plasmonic TiN nanoparticles. The VO2 /TiN
coatings can control infrared (IR) radiation dynamically in accordance with the
ambient temperature and illumination intensity. It blocks IR light under strong
illumination at 28 degrees C but is IR transparent under weak irradiation
conditions or at a low temperature of 20 degrees C. The VO2 /TiN coatings
exhibit a good integral visible transmittance of up to 51% and excellent IR
switching efficiency of 48% at 2000 nm. These unique advantages make VO2 /TiN
promising as smart energy-saving windows.
PMID- 29349815
TI - Erratum: An assessment of differences in costs and health benefits of serology
and NAT screening of donations for blood transfusion in different Western
countries.
PMID- 29349817
TI - Anatomical study of the so-called "retromolar gland": Distinguishing normal
anatomy from oral cavity pathology.
AB - The minor salivary glands in the retromolar trigone have rarely been studied. The
aim of this study was to better define the anatomy of the minor salivary glands
in the retromolar trigone and establish the relationships between these and
adjacent structures. The gland in the retromolar trigone was exposed and its
relationships to surrounding structures were observed on 20 cadaveric sides. The
boundaries of the gland included the superior pharyngeal constrictor muscle, the
tendon of the buccinator muscle, and loose connective tissue. The gland was not
continuous with the pterygomandibular or parapharyngeal spaces, but loose
connective tissue was present between glands in the retromolar trigone and the
medial pterygoid muscle. To our knowledge, this is the first study to describe
the detailed anatomy of the minor salivary gland in the retromolar trigone. We
suggest that the minor salivary gland in the retromolar trigone should be named
the "retromolar gland." Clin. Anat. 31:462-465, 2018. (c) 2018 Wiley Periodicals,
Inc.
PMID- 29349818
TI - Nanocrystalline Precursors for the Co-Assembly of Crack-Free Metal Oxide Inverse
Opals.
AB - Inorganic microstructured materials are ubiquitous in nature. However, their
formation in artificial self-assembly systems is challenging as it involves a
complex interplay of competing forces during and after assembly. For example,
colloidal assembly requires fine-tuning of factors such as the size and surface
charge of the particles and electrolyte strength of the solvent to enable
successful self-assembly and minimize crack formation. Co-assembly of templating
colloidal particles together with a sol-gel matrix precursor material helps to
release stresses that accumulate during drying and solidification, as previously
shown for the formation of high-quality inverse opal (IO) films out of amorphous
silica. Expanding this methodology to crystalline materials would result in
microscale architectures with enhanced photonic, electronic, and catalytic
properties. This work describes tailoring the crystallinity of metal oxide
precursors that enable the formation of highly ordered, large-area (mm2 ) crack
free titania, zirconia, and alumina IO films. The same bioinspired approach can
be applied to other crystalline materials as well as structures beyond IOs.
PMID- 29349819
TI - Incidence and predictors of sudden cardiac death after heart transplantation: A
systematic review and meta-analysis.
AB - PURPOSE: Sudden cardiac death (SCD) is an important post-transplant problem being
responsible for ~10% of deaths. We conducted a systematic review and meta
analysis to evaluate incidence and predictors of post-heart transplant SCD and
the use of implantable cardiac defibrillator (ICD). METHODS: Citations were
identified in electronic databases and references of included studies.
Observational studies on adults reporting on incidence and predictors of post
transplant SCD and ICD use were selected. We meta-analyzed SCD in person-years
using random effects models. We qualitatively summarized predictors. RESULTS:
This study includes 55 studies encompassing 47 901 recipients. The pooled
incidence rate of SCD was 1.30 per 100 person-years (95% CI: 1.08-1.52). Cardiac
allograft vasculopathy (CAV) was associated with higher SCD risk (2.40 per 100
patient-years, 95% CI: 1.46-3.34). Independent predictors of SCD identified by
two moderate-quality studies were older donor age, younger recipient age, non
Caucasian race, reduced left ventricular ejection fraction, rejection, infection,
and cancer. Authors rarely reported on ICD use. CONCLUSION: This meta-analysis
found that post-transplant SCD risk in heart transplant recipients is higher than
that in the general population. CAV was associated with increased SCD risk.
Observational studies reporting on absolute risk of SCD are needed to better
identify populations at a clinically significant increased risk.
PMID- 29349820
TI - An experimental test of alternative population augmentation scenarios.
AB - Human land use is fragmenting habitats worldwide and inhibiting dispersal among
previously connected populations of organisms, often leading to inbreeding
depression and reduced evolutionary potential in the face of rapid environmental
change. To combat this augmentation of isolated populations with immigrants is
sometimes used to facilitate demographic and genetic rescue. Augmentation with
immigrants that are genetically and adaptively similar to the target population
effectively increases population fitness, but if immigrants are very genetically
or adaptively divergent, augmentation can lead to outbreeding depression. Despite
well-cited guidelines for the best practice selection of immigrant sources, often
only highly divergent populations remain, and experimental tests of these riskier
augmentation scenarios are essentially nonexistent. We conducted a mesocosm
experiment with Trinidadian guppies (Poecilia reticulata) to test the
multigenerational demographic and genetic effects of augmenting 2 target
populations with 3 types of divergent immigrants. We found no evidence of
demographic rescue, but we did observe genetic rescue in one population.
Divergent immigrant treatments tended to maintain greater genetic diversity,
abundance, and hybrid fitness than controls that received immigrants from the
source used to seed the mesocosms. In the second population, divergent immigrants
had a slightly negative effect in one treatment, and the benefits of augmentation
were less apparent overall, likely because this population started with higher
genetic diversity and a lower reproductive rate that limited genetic admixture.
Our results add to a growing consensus that gene flow can increase population
fitness even when immigrants are more highly divergent and may help reduce
uncertainty about the use of augmentation in conservation.
PMID- 29349821
TI - Biodegradable Electronic Systems in 3D, Heterogeneously Integrated Formats.
AB - Biodegradable electronic systems represent an emerging class of technology with
unique application possibilities, from temporary biomedical implants to "green"
consumer gadgets. This paper introduces materials and processing methods for 3D,
heterogeneously integrated devices of this type, with various functional examples
in sophisticated forms of silicon-based electronics. Specifically, techniques for
performing multilayer assembly by transfer printing and for fabricating layer-to
layer vias and interconnects by lithographic procedures serve as routes to
biodegradable, 3D integrated circuits composed of functional building blocks
formed using specialized approaches or sourced from commercial semiconductor
foundries. Demonstration examples range from logic gates and analog circuits that
undergo functional transformation by transience to systems that integrate
multilayer resistive sensors for in situ, continuous electrical monitoring of the
processes of transience. The results significantly expand the scope of
engineering options for biodegradable electronics and other types of transient
microsystem technologies.
PMID- 29349822
TI - Subcritical water extraction of amino acids from Mars analog soils.
AB - For decades, the Martian regolith has stymied robotic mission efforts to catalog
the organic molecules present. Perchlorate salts, found widely throughout Mars,
are the main culprit as they breakdown and react with organics liberated from the
regolith during pyrolysis, the primary extraction technique attempted to date on
Mars. This work further develops subcritical water extraction (SCWE) as a
technique for extraction of amino acids on future missions. The effect of SCWE
temperature (185, 200, and 215 degrees C) and duration of extraction (10-120 min)
on the total amount and distribution of amino acids recovered was explored for
three Mars analog soils (JSC Mars-1A simulant, an Atacama desert soil, and an
Antarctic Dry Valleys soil) and bovine serum albumin (as a control solution of
known amino acid content). Total amounts of amino acids extracted increased with
both time and temperature; however, the distribution shifted notably due to the
destruction of the amino acids with charged or polar side chains at the higher
temperatures. The pure bovine serum albumin solution and JSC Mars 1A also showed
lower yields than the Atacama and Antarctic extractions suggesting that SCWE may
be less effective at hydrolyzing large or aggregated proteins. Changing solvent
from water to a dilute (10 mM) HCl solution allowed total extraction efficiencies
comparable to the higher temperature/time combinations while using the lowest
temperature/time (185 degrees C/20 min). The dilute HCl extractions also did not
lead to the shift in amino acid distribution observed at the higher temperatures.
Additionally, adding sodium perchlorate salt to the extraction did not interfere
with recoveries. Native magnetite in the JSC Mars-1A may have been responsible
for destruction of glycine, as evidenced by its uncharacteristic decrease as the
temperature/time of extraction increased. This work shows that SCWE can extract
high yields of native amino acids out of Mars analog soils with minimal
disruption of the distribution of those amino acids, even in the presence of a
perchlorate salt.
PMID- 29349823
TI - Tibolone and risk of gynecological hormone sensitive cancer.
AB - Risk of ovarian cancer with hormone therapy is associated with use of both
unopposed estrogen therapy and combined estrogen-progestin therapy, whereas for
endometrial cancer addition of continuous progestin decreases the estrogen
induced increased risk. Less is known about risk with use of tibolone; a
synthetic steroid with estrogenic, progestagenic and androgenic properties. We
assessed these associations in a prospective cohort study, including all Danish
women 50-79 years of age and followed 1995-2009. National Danish Registers
captured individually updated exposure information, cancer cases including
histology and confounding factors. Poisson regression analyses provided multiple
adjusted incidence rate ratios (IRRs). More than 900,000 women were followed for
9.8 years on average; 4,513 were diagnosed with ovarian cancer and 6,202 with
endometrial cancer. Compared to women never on postmenopausal hormone therapy,
current users of tibolone had an increased IRR for ovarian cancer (1.42(95%
confidence interval [CI], 1.01-2.00) and serous ovarian tumors (2.21(95%CI 1.48
3.32)). The risk increased with duration of use, particularly for serous ovarian
tumors. Compared to never users, the IRR of endometrial cancer was 3.56(95%CI
2.94-4.32) among current users of tibolone and 3.80(95%CI 3.08-4.69) of Type I
endometrial cancer. The steepest risk increase with duration of use was for Type
I tumors. In conclusion, tibolone is associated with increased risk for ovarian
and endometrial cancer overall; and particular the risk of serous ovarian tumors
and Type I endometrial cancer. Because the associations are stronger with
increasing durations of use - and for hormone sensitive tumors - the results seem
indicative of causality.
PMID- 29349824
TI - Reduced left ventricular filling following blood volume extraction does not
result in compensatory augmentation of cardiac mechanics.
AB - NEW FINDINGS: What is the central question of this study? A reduction in left
ventricular (LV) filling, and concomitant increase in heart rate, augments LV
mechanics to maintain stroke volume (SV); however, the impact of reduced LV
filling in isolation on SV and LV mechanics is currently unknown. What is the
main finding and its importance? An isolated decrease in LV filling did not
provoke a compensatory increase in mechanics to maintain SV; in contrast, LV
mechanics and SV were reduced. These data indicate that when LV filling is
reduced without changes in heart rate, LV mechanics do not compensate to maintain
SV. ABSTRACT: An acute non-invasive reduction in preload has been shown to
augment cardiac mechanics to maintain stroke volume and cardiac output. Such
interventions induce concomitant changes in heart rate, whereas blood volume
extraction reduces preload without changes in heart rate. Therefore, the purpose
of this study was to determine whether a preload reduction in isolation resulted
in augmented stroke volume achieved via enhanced cardiac mechanics. Nine healthy
volunteers (four female, age 29 +/- 11 years) underwent echocardiography for the
assessment of left ventricular (LV) volumes and mechanics in a supine position at
baseline and end extraction after the controlled removal of 25% of total blood
volume (1062 +/- 342 ml). Arterial blood pressure was monitored continuously by a
pressure transducer attached to an indwelling radial artery catheter. Heart rate
and total peripheral resistance were unchanged from baseline to end extraction,
but systolic blood pressure was reduced (from 148 to 127 mmHg). From baseline to
end extraction there were significant reductions in left ventricular end
diastolic volume (from 89 to 71 ml) and stroke volume (from 56 to 37 ml);
however, there was no change in LV twist, basal or apical rotation. In contrast,
LV longitudinal strain (from -20 to -17%) and basal circumferential strain (from
22 to -19%) were significantly reduced from baseline to end extraction. In
conclusion, a reduction in preload during blood volume extraction does not result
in compensatory changes in stroke volume or cardiac mechanics. Our data suggest
that LV strain is dependent on LV filling and consequent geometry, whereas LV
twist could be mediated by heart rate.
PMID- 29349825
TI - Synthesis of Single and Double Dibenzohelicenes by Rhodium-Catalyzed
Intramolecular [2+2+2] and [2+1+2+1] Cycloaddition.
AB - Dibenzo[7]helicenes were synthesized with up to 99 % ee by rhodium(I)/binap
catalyzed enantioselective intramolecular [2+2+2] cycloaddition of 2
phenylnaphthalene-linked triynes. Additionally, [2+1+2+1] cycloaddition products,
that is, twisted anthracenes, were also synthesized by using difluorphos as
ligand. Although these compounds are not configurationally stable at elevated
temperature, their Scholl reactions afforded configurationally stable double
dibenzo[6]helicenes. The thus-obtained dibenzo[7]helicene exhibited good
circularly polarized luminescence property and the double dibenzo[6]helicene
showed high fluorescence quantum yield.
PMID- 29349826
TI - Low performance on mathematical tasks in preschoolers: the importance of domain
general and domain-specific abilities.
AB - BACKGROUND: Different domain-specific and domain-general cognitive precursors
play a key role in the development of mathematical abilities. The contribution of
these domains to mathematical ability changes during development. Primary school
aged children who show mathematical difficulties form a heterogeneous group, but
it is not clear whether this also holds for preschool low achievers (LAs) and how
domain-specific and domain-general abilities contribute to mathematical
difficulties at a young age. The aim of this study was to explore the cognitive
characteristics of a sample of preschool LAs and identify sub-types of LAs.
METHODS: 81 children were identified as LAs from 283 preschoolers aged 3 to 5
years old and were assessed on a number of domain-general and domain-specific
tasks. RESULTS: Cluster analysis revealed four subgroups of LAs in mathematics:
(1) a weak processing sub-type; (2) a general mathematical LAs sub-type; (3) a
mixed abilities sub-type; and (4) a visuo-spatial deficit sub-type. Whilst two of
the groups showed specific domain-general difficulties, none showed only domain
specific difficulties. CONCLUSIONS: Current findings suggest that preschool LAs
constitute a heterogeneous group and stress the importance of domain-general
factors for the development of mathematical abilities during the preschool years.
PMID- 29349827
TI - Underwater Mechanically Robust Oil-Repellent Materials: Combining Conflicting
Properties Using a Heterostructure.
AB - The development of underwater mechanically robust oil-repellent materials is
important due to the high demand for these materials with the increase in
underwater activities. Based on the previous study, a new strategy is
demonstrated to prepare underwater mechanically robust oil-repellent materials by
combining conflicting properties using a heterostructure, which has a layered
hydrophobic interior structure with a columnar hierarchical micro/nanostructure
on the surface and a hydrophilic outer structure. The surface hydrophilic layer
imparts underwater superoleophobicity and low oil adhesion to the material, which
has oil contact angle of larger than 150 degrees and adhesion of lower than 2.8
uN. The stability of the mechanical properties stemming from the interior
hydrophobic-layered structure enables the material to withstand high weight loads
underwater. The tensile stress and the hardness of such a heterostructure film
after 1 month immersion in seawater and pH solution are in the range from 83.92
+/- 8.22 to 86.73 +/- 7.8 MPa and from 83.88 +/- 6.8 to 86.82 +/- 5.64 MPa,
respectively, which are superior to any underwater oil-repellent material
currently reported.
PMID- 29349828
TI - Further Evidence That Sleep Deprivation Effects and the Vigilance Decrement Are
Functionally Equivalent: Comment on Altmann (2018).
AB - Veksler and Gunzelmann (2018) argue that the vigilance decrement and the
deleterious effects of sleep loss reflect functionally equivalent degradations in
cognitive processing and performance. Our account is implemented in a cognitive
architecture, where these factors produce breakdowns in goal-directed cognitive
processing that we refer to as microlapses. Altmann (2018) raises a number of
challenges to microlapses as a unified account of these deficits. Under scrutiny,
however, the challenges do little to discredit the theory or conclusions in the
original paper. In our response, we address the most serious challenges. In so
doing, we provide additional support for the theory and mechanisms, and we
highlight opportunities for extending their explanatory breadth.
PMID- 29349829
TI - Physicians' perspective on the clinical meaningfulness of inflammatory bowel
disease trial results: an International Organization for the Study of
Inflammatory Bowel Disease (IOIBD) survey.
AB - BACKGROUND: Several novel compounds are being developed for inflammatory bowel
diseases (IBD). In addition, biosimilar drugs are being approved. An increasing
number of head-to-head, superiority and non-inferiority trials in patients with
IBD are expected in the future. The clinical relevance of the magnitude of the
effect size is often debated. AIM: To better understand physicians' perspectives
on the clinical meaningfulness of IBD trial results. METHODS: We conducted an
online survey among all IOIBD (International Organization for the Study of
Inflammatory Bowel Diseases) members, asking their opinion on the clinical
relevance of the results of IBD trials. RESULTS: Forty-six IOIBD members
responded to the survey (52.3%). In biologic-naive ulcerative colitis (UC) and
Crohn's disease (CD) patients, most of the participants considered a 15%
difference with placebo for clinical remission and endoscopic remission to be
clinically relevant. In head-to-head trials, most of participants considerer a
10% difference between groups for clinical remission and endoscopic remission to
be clinically relevant. Half of respondents considered 10% to be an adequate
margin in non-inferiority trials. In bioequivalence studies, most of the
participants considered adequate a +/- 5% difference between a biosimilar and the
originator for pharmacokinetic parameters, efficacy, safety and immunogenicity.
Regarding safety, the difference between two drugs considered clinically relevant
varied from 1% to 5%, depending on the type of adverse event. CONCLUSIONS: This
is the first survey exploring how physicians perceive IBD trial results,
providing an estimation of the magnitude of the difference between treatment arms
that may directly influence clinical practice.
PMID- 29349830
TI - Synthesis and Structure of a Longitudinally Twisted Hexacene.
AB - The addition of phenyllithium to a polycyclic quinone, 9,11,12,21,22,24
hexaphenyltetrabenzo[a,c,n,p]hexacene-10,23-dione (10), followed by SnCl2
mediated reduction of the diol intermediate, yielded 9,10,11,12,21,22,23,24
octaphenyltetrabenzo-[a,c,n,p]hexacene (4). Crystallographic analysis of hexacene
4 showed it to possess a longitudinal twist of 184 degrees , which was in good
agreement with AM1 calculations. In addition to being the most twisted acene
synthesized to this point, compound 4 contains within its substructure the most
twisted naphthalene, anthracene, tetracene, and pentacene moieties described.
PMID- 29349832
TI - Effects of yoga interventions practised in heated and thermoneutral conditions on
endothelium-dependent vasodilatation: The Bikram yoga heart study.
AB - NEW FINDINGS: What is the central question of this study? Does the heated
practice environment enhance the effects of Bikram yoga on endothelium-dependent
vasodilatation in healthy, middle-aged adults? What is the main finding and its
importance? The primary finding from this investigation is that the hatha yoga
postures in the Bikram yoga series produce similar enhancements in endothelium
dependent vasodilatation in healthy, middle-aged adults regardless of
environmental temperature. These findings highlight the efficacy of yoga postures
in producing improvements in vascular health and downplay the necessity of the
heated practice environment in inducing vascular adaptations. ABSTRACT: We have
previously documented improvements in endothelium-dependent vasodilatation with a
Bikram (hot) yoga intervention in middle-aged adults. At present, the effect of
environmental temperature in hot yoga on endothelial function is unknown. The
purpose of this investigation was to determine the effects of Bikram yoga
interventions performed in heated or thermoneutral conditions on endothelium
dependent vasodilatation. Fifty-two sedentary but apparently healthy adults aged
40-60 years were randomly assigned to one of three groups: Bikram yoga practised
at 40.5 degrees C (n = 19), Bikram yoga practised at 23 degrees C (n = 14) or
sedentary time control (n = 19). The yoga interventions consisted of 90 min
Bikram yoga classes three times a week for 12 weeks. Endothelium-dependent
vasodilatation was measured non-invasively using brachial artery flow-mediated
dilatation (FMD). Body fat percentage determined via dual-energy X-ray
absorptiometry was significantly lower in the hot yoga group after the
intervention than in the thermoneutral yoga and control conditions. Brachial
artery FMD increased (P < 0.05) in the thermoneutral yoga group and tended to
increase in the hot yoga group (P = 0.056). No changes occurred in the control
group. There were no significant differences in FMD change scores between groups.
We conclude that Bikram yoga practised in thermoneutral conditions improved
endothelium-dependent vasodilatation in healthy, middle-aged adults. These new
findings highlight the effectiveness of hatha yoga postures alone, in the absence
of a heated practice environment, in improving vascular health and are of
clinical significance given the increased propensity for heat intolerance in
ageing adults.
PMID- 29349833
TI - A systematic assessment of key design and performance characteristics of drug
exposure registries requested by the U.S. Food and Drug Administration.
AB - PURPOSE: The purpose of the study is to evaluate contributions to postmarket
safety assessments and identify potential factors for enhancing implementation
and utilization of registries in regulatory decision-making. METHODS: Registry
documents (e.g., protocols, reports) submitted to the FDA were identified up to
January 2016 through an extensive, systematic review of internal records and
resources. We characterized nonpregnancy drug exposure registries based on
prespecified design elements, performance, and regulatory impact. RESULTS: A
total of 65 registries were identified: 56 registries were open and 9 closed.
Among open registries, 20% were pending, 14% delayed, and 16% ongoing less than
<=3 years. Most registries (82%) examined safety issues that originally arose
from clinical trials; most frequent safety issues investigated included
infections, gastrointestinal dysfunction, and liver toxicity. Although 74% of
registries ascertained baseline health conditions and monitored concomitant
medication use, fewer (45%) considered drug exposure duration or dosage. Thirty
seven percent of non pending registries had enrollment below sample size
expectation. Seventeen registries published findings in journals/conference
proceedings, 13 from open registries. Three closed registries generated results
that contributed to product label changes. High-performance registries scored
higher in design metrics related to sample size considerations (76% versus 62%)
and adequate analysis plan (53% versus 35%), and interim report submission (76%
versus 65%). There was a significant difference in proportion of registries with
clear primary objectives between high versus not high performing registries (100%
versus 78%). CONCLUSIONS: This study suggests clear objectives, patient
accrual/retention efforts, adequate analysis plans, and interim reports
contribute to the performance of drug exposure registries.
PMID- 29349831
TI - Aortic dysfunction in metabolic syndrome mediated by perivascular adipose tissue
TNFalpha- and NOX2-dependent pathway.
AB - NEW FINDINGS: What is the central question of this study? Tumour necrosis factor
alpha (TNFalpha) has been shown to impair vascular function, but the impact of
thoracic aorta perivascular adipose tissue (tPVAT)-derived TNFalpha on tPVAT and
aortic function in metabolic syndrome is unknown. What is the main finding and
its importance? Release of TNFalpha by tPVAT causes production of reactive oxygen
species in tPVAT through activation of an NADPH-oxidase 2 (NOX2)-dependent
pathway, activates production of aortic reactive oxygen species and mediates
aortic stiffness, potentially through matrix metalloproteinase 9 activity.
Neutralization of TNFalpha and/or inhibition of NOX2 blocks the tPVAT-induced
impairment of aortic function. These data partly implicate tPVAT NOX2 and
TNFalpha in mediating the vascular pathology of metabolic syndrome. ABSTRACT:
Perivascular adipose tissue (PVAT) is recognized for its vasoactive effects, but
it is unclear how metabolic syndrome impacts thoracic aorta (t)PVAT and the
subsequent effect on functional and structural aortic stiffness. Thoracic aorta
and tPVAT were removed from 16- to 17-week-old lean (LZR, n = 16) and obese
Zucker rats (OZR, n = 16). The OZR presented with aortic endothelial dysfunction,
assessed by wire myography, and increased aortic stiffness, assessed by elastic
modulus. The OZR tPVAT exudate further exacerbated the endothelial dysfunction,
reducing nitric oxide and endothelium-dependent relaxation (P < 0.05).
Additionally, OZR tPVAT exudate had increased MMP9 activity (P < 0.05) and
further increased the elastic modulus of the aorta after 72 h of co-culture (P <
0.05). We found that the observed aortic dysfunction caused by OZR tPVAT was
mediated through increased production and release of tumour necrosis factor-alpha
(TNFalpha; P < 0.01), which was dependent on tPVAT NADPH-oxidase 2 (NOX2)
activity. The OZR tPVAT release of reactive oxygen species and subsequent aortic
dysfunction were inhibited by TNFalpha neutralization and/or inhibition of NOX2.
Additionally, we found that OZR tPVAT had reduced activity of the active sites of
the 20S proteasome (P < 0.05) and reduced superoxide dismutase activity (P <
0.01). In conclusion, metabolic syndrome causes tPVAT dysfunction through an
interplay between TNFalpha and NOX2 that leads to tPVAT-mediated aortic stiffness
by activation of aortic reactive oxygen species and increased MMP9 activity.
PMID- 29349834
TI - Drug adherence in treatment resistant and in controlled hypertension-Results from
the Swedish Primary Care Cardiovascular Database (SPCCD).
AB - PURPOSE: To assess drug adherence in patients treated with >=3 antihypertensive
drug classes, with both controlled and uncontrolled blood pressure and describe
associated factors for nonadherence. METHODS: Patients with hypertension, without
cardiovascular comorbidity, aged >30 years treated with >=3 antihypertensive drug
classes were followed for 2 years. Both patients with treatment resistant
hypertension (TRH) and patients with controlled hypertension were included.
Clinical data were derived from a primary care database. Pharmacy refill data
from the Swedish Prescribed drug registry was used to calculate proportion of
days covered (PDC). Patients with a PDC level >= 80% were included. RESULTS: We
found 5846 patients treated >=3 antihypertensive drug classes, 3508 with TRH
(blood pressure >= 140/90), and 2338 with controlled blood pressure (<140/90 mm
Hg). TRH patients were older (69.1 vs 65.8 years, P < .0001) but had less
diabetes (28.5 vs 31.7%, P < .009) compared with patients with controlled blood
pressure. The proportion of patients with PDC >= 80% declined with 11% during the
first year in both groups. Having diabetes was associated with staying adherent
at 1 year (RR 0.82; 95% CI, 0.68-0.98) whilst being born outside Europe was
associated with nonadherence at one and (RR 2.05; 95% CI, 1.49-2.82).
CONCLUSIONS: Patients with multiple antihypertensive drug therapy had similar
decline in adherence over time regardless of initial blood pressure control.
Diabetes was associated with better adherence, which may imply that the
structured caregiving of these patients enhances antihypertensive drug treatment.
PMID- 29349836
TI - Evaluation of a West Australian residential mental health respite service.
AB - Family members continue to be the predominant providers of support, care and
accommodation for loved ones with mental health issues, and empirical studies
suggest that accessing mental health respite can be helpful for both carers and
consumers. However, the availability of, and access to, this respite in Australia
is far from optimal. Major issues have also been identified such as low
utilisation, the inappropriate and inflexible nature of services and the
inability of services to respond to situations where multiple needs exist. This
article presents findings from a small evaluation of a pilot residential respite
service. Semi-structured interviews were conducted with eight family
members/carers and four consumers using the service, and five service providers.
In addition, anonymised sociodemographic information about all users of the
service in the first 9 months of its operation were analysed. Reflecting the
current limitations around respite options, the majority of family members/carers
and consumers were appreciative of, and satisfied with, the service. The research
highlighted issues such as availability and suitability of respite, particularly
when consumers had multiple and unmet needs. Mental health residential respite is
often a stopgap in crisis situations and intersects with the difficulty of
planning respite and shortages in affordable supported accommodation.
Furthermore, the ramifications of individualised funding for people with
"psychosocial disability" in the new Australian National Disability Insurance
Scheme (NDIS) remain unclear. While family members and carers may benefit
indirectly from NDIS funding, it is especially important at this time that the
need for more suitable, recovery-oriented respite services is highlighted.
PMID- 29349835
TI - Optimization of Aqueous Extraction from Kalanchoe pinnata Leaves to Obtain the
Highest Content of an Anti-inflammatory Flavonoid using a Response Surface Model.
AB - INTRODUCTION: The medicinal plant Kalanchoe pinnata is a phenolic-rich species
used worldwide. The reports on its pharmacological uses have increased by 70% in
the last 10 years. The leaves of this plant are the main source of an unusual
quercetin-diglycosyl flavonoid (QAR, quercetin arabinopyranosyl
rhamnopyranoside), which can be easily extracted using water. QAR possess a
strong in vivo anti-inflammatory activity. OBJECTIVE: To optimize the aqueous
extraction of QAR from K. pinnata leaves using a three-level full factorial
design. MATERIAL AND METHODS: After a previous screening design, time (x1 ) and
temperature (x2 ) were chosen as the two independent variables for optimization.
Freeze-dried leaves were extracted with water (20% w/v), at 30 degrees C, 40
degrees C or 50 degrees C for 5, 18 or 30 min. QAR content (determined by HPLC
DAD) and yield of extracts were analyzed. The optimized extracts were also
evaluated for cytotoxicity. RESULTS: The optimal heating times for extract yield
and QAR content were similar in two-dimensional (2D) surface responses (between
12.8 and 30 min), but their optimal extraction temperatures were ranged between
40 degrees C and 50 degrees C for QAR content and 30 degrees C and 38 degrees C
for extract yield. A compromise region for both parameters was at the mean points
that were 40 degrees C for the extraction temperature and 18 min for the total
time. CONCLUSION: The optimized process is faster and spends less energy than the
previous one (water; 30 min at 55 degrees C); therefore is greener and more
attractive for industrial purposes. This is the first report of extraction
optimization of this bioactive flavonoid. Copyright (c) 2018 John Wiley & Sons,
Ltd.
PMID- 29349837
TI - Human-specific phages infecting Enterococcus host strain MW47: are they reliable
microbial source tracking markers?
AB - AIM: The aim of this study was to determine the morphological diversity and
environmental survival of human-specific phages infecting Enterococcus faecium
host strain MW47, to support their use as microbial source tracking (MST)
markers. METHODS AND RESULTS: Twenty phages capable of infecting strain MW47 were
propagated and their morphologies were determined using transmission electron
microscopy (TEM), which revealed that a heterogeneous group of phages was able to
infect strain MW47. Three distinct morphologies from two different families
(Myoviridae and Siphoviridae) were observed. In situ inactivation experiments
were subsequently conducted to determine their environmental persistence.
CONCLUSION: The findings revealed a statistically significant link between
morphology and the rate of inactivation, with phages belonging to the Myoviridae
family demonstrating more rapid inactivation in comparison to those belonging to
the Siphoviridae family. SIGNIFICANCE AND IMPACT OF STUDY: The results suggest
that while Enterococcus MW47 phages appear to be a potentially valuable MST
tools, significant variations in the persistence of the different phages mean
that the approach should be used with caution, as this may adversely affect the
reliability of the approach, especially when comparing MW47 phage levels or the
presence across different matrices (e.g. levels in sediments or shellfish). This
highlights the importance of elucidating the ecological characteristics of newly
proposed MST markers before they are used in full-scale MST investigations.
PMID- 29349838
TI - Patent foramen ovale repair at the time of double lung transplantation: Necessary
or not?
AB - INTRODUCTION: Patient foramen ovale (PFO) is a common and often incidental
intraoperative finding during lung transplantation (LTx). We sought to
characterize the potential outcomes related to the decision making of whether the
PFO was repaired or left unrepaired. METHODS: We retrospectively evaluated
bilateral LTx recipients between 2005 and 2015 from our prospective database.
Incidence of postoperative stoke, 90-day mortality, and overall survival was
compared between the PFO-positive and PFO-negative groups, and secondly compared
between repaired PFO (rPFO) and non-repaired PFO (nrPFO) groups. RESULTS: A total
of 831 LTx recipients were analyzed: 185 PFO-positive (140 nrPFO, 45 rPFO) and
646 PFO-negative. Study groups were similar with regard to age and comorbidity.
The presence of PFO was not associated with a difference in postoperative stroke
(P = .89) or 90-day mortality (P = .64). In patients with PFO, intraoperative
repair resulted in a lower, but non-significant rate of stroke (0% vs 5%; P =
.20) and no difference in mortality (P = .26). As expected, PFO and PFO repair
were both associated with a higher incidence of cardiopulmonary bypass
utilization, but no difference in pump-related complications. CONCLUSIONS: The
protective effect of PFO repair remains unclear. However, it is not associated
with an increased incidence of stroke or postoperative mortality following LTx.
PMID- 29349839
TI - Inflammatory biomarkers and intellectual disability in patients with Down
syndrome.
AB - BACKGROUND: Intellectual disability (ID) is part of the Down syndrome (DS)
phenotypic spectrum, but the exact molecular pathophysiology of ID in individuals
with DS is not yet fully understood, with many research hypotheses still
unproven. Basing on previous studies (which suggested a possible role of altered
inflammatory response in DS-related ID), we assessed the serum levels of a number
of inflammatory biomarkers [serum amyloid A (SAA), C-reactive protein (C-RP),
high mobility group box-1 (HMGB1)] in a cohort of individuals with DS and healthy
controls. METHODS: In total, 24 children diagnosed with DS and 12 healthy
controls were enrolled, and all underwent detailed cognitive assessment. Also,
serum SAA, C-RP and HMGB1 levels were measured in all recruited subjects and
correlated to the severity of ID in the DS group. RESULTS: Serum SAA, C-RP and
HMGB1 values were found to be significantly higher in the DS group compared with
the healthy subjects (P = 0.001). In addition, serum HMGB1 levels positively
correlated with C-RP and SAA in the DS group but not in the healthy controls.
Only serum C-RP levels resulted inversely correlated (P < 0.01) with intelligence
quotient (IQ); conversely, significant statistical correlations between serum SAA
levels and IQ (as well as between HMGB1 and IQ) have been not found (P > 0.05).
CONCLUSIONS: The levels of the determined markers were higher in DS individuals
compared with (cognitively) healthy subjects, and CRP showed a negative
correlation with IQ in children with DS.
PMID- 29349840
TI - The Preference for Pointing With the Hand Is Not Universal.
AB - Pointing is a cornerstone of human communication, but does it take the same form
in all cultures? Manual pointing with the index finger appears to be used
universally, and it is often assumed to be universally preferred over other
forms. Non-manual pointing with the head and face has also been widely attested,
but it is usually considered of marginal significance, both empirically and
theoretically. Here, we challenge this assumed marginality. Using a novel
communication task, we investigated pointing preferences in the Yupno of Papua
New Guinea and in U.S. undergraduates. Speakers in both groups pointed at similar
rates, but form preferences differed starkly: The Yupno participants used non
manual pointing (nose- and head-pointing) numerically more often than manual
pointing, whereas the U.S. participants stuck unwaveringly to index-finger
pointing. The findings raise questions about why groups differ in their pointing
preferences and, more broadly, about why humans communicate in the ways they do.
PMID- 29349841
TI - Novel MOF-Derived Co@N-C Bifunctional Catalysts for Highly Efficient Zn-Air
Batteries and Water Splitting.
AB - Metal-organic frameworks (MOFs) and MOF-derived materials have recently attracted
considerable interest as alternatives to noble-metal electrocatalysts. Herein,
the rational design and synthesis of a new class of Co@N-C materials (C-MOF-C2-T)
from a pair of enantiotopic chiral 3D MOFs by pyrolysis at temperature T is
reported. The newly developed C-MOF-C2-900 with a unique 3D hierarchical rodlike
structure, consisting of homogeneously distributed cobalt nanoparticles
encapsulated by partially graphitized N-doped carbon rings along the rod length,
exhibits higher electrocatalytic activities for oxygen reduction and oxygen
evolution reactions (ORR and OER) than that of commercial Pt/C and RuO2 ,
respectively. Primary Zn-air batteries based on C-MOF-900 for the oxygen
reduction reaction (ORR) operated at a discharge potential of 1.30 V with a
specific capacity of 741 mA h gZn-1 under 10 mA cm-2 . Rechargeable Zn-air
batteries based on C-MOF-C2-900 as an ORR and OER bifunctional catalyst exhibit
initial charge and discharge potentials at 1.81 and 1.28 V (2 mA cm-2 ), along
with an excellent cycling stability with no increase in polarization even after
120 h - outperform their counterparts based on noble-metal-based air electrodes.
The resultant rechargeable Zn-air batteries are used to efficiently power
electrochemical water-splitting systems, demonstrating promising potential as
integrated green energy systems for practical applications.
PMID- 29349842
TI - Is "end of life" a special case? Connecting Q with survey methods to measure
societal support for views on the value of life-extending treatments.
AB - Preference elicitation studies reporting societal views on the relative value of
end-of-life treatments have produced equivocal results. This paper presents an
alternative method, combining Q methodology and survey techniques (Q2S) to
determine the distribution of 3 viewpoints on the relative value of end-of-life
treatments identified in a previous, published, phase of this work. These were
Viewpoint 1, "A population perspective: value for money, no special cases";
Viewpoint 2, "Life is precious: valuing life-extension and patient choice"; and
Viewpoint 3, "Valuing wider benefits and opportunity cost: the quality of life
and death." A Q2S survey of 4,902 respondents across the United Kingdom measured
agreement with these viewpoints; 37% most agreed with Viewpoint 1, 49% with
Viewpoint 2, and 9% with Viewpoint 3. Regression analysis showed associations of
viewpoints with gender, level of education, religion, voting preferences, and
satisfaction with the NHS. The Q2S approach provides a promising means to
investigate how in-depth views and opinions are represented in the wider
population. As demonstrated in this study, there is often more than 1 viewpoint
on a topic and methods that seek to estimate that averages may not provide the
best guidance for societal decision-making.
PMID- 29349844
TI - Exploration of joint working practices on anti-social behaviour between criminal
justice, mental health and social care agencies: A qualitative study.
AB - Although the police play an important role for people with mental health problems
in the community, little is known about joint working practices between mental
health, social care and police services. There is potential for tensions and
negative outcomes for people with mental health problems, in particular when the
focus is on behaviours that could be interpreted as anti-social. This study
explores perceptions about joint working between mental health, social care and
police services with regard to anti-social behaviour. We conducted a multi-method
sequential qualitative study in the UK collecting data between April 2014 and
August 2016. Data were collected from two study sites: 60 narrative police logs
of routinely gathered information, and semi-structured interviews and focus
groups with professionals from a range of statutory and third sector
organisations (N = 55). Data sets were analysed individually, using thematic
iterative coding before integrating the findings. We also looked at sequencing
and turning points in the police logs. Findings mapped on a continuum of joint
working practices, with examples more likely to be away from the policy ideal of
partnership working as being central to mainstream activities. Joint working was
driven by legal obligations and concerns about risk rather than a focus on the
needs of a person with mental health problems. This was complicated by different
perceptions of the police role in mental health. Adding anti-social behaviour to
this mix intensified challenges as conceptualisation of the nature of the problem
and agreeing on best practice and care is open to interpretations and judgements.
Of concern is an evident lack of awareness of these issues. There is a need to
reflect on joint working practices, including processes and goals, keeping in
mind the health and welfare needs of people with mental health problems.
PMID- 29349843
TI - Pregnancy after bariatric surgery: Maternal and fetal outcomes of 39 pregnancies
and a literature review.
AB - AIM: We aimed to evaluate the impact of bariatric surgery (BS) on maternal and
fetal outcomes. METHODS: A retrospective, descriptive, observational study of 39
pregnant women who underwent BS in our institution between 2010 and 2014 was
carried out. A sample of women who became pregnant after BS was evaluated, based
on data concerning pregnancy, childbirth, and newborns. RESULTS: Of the 1182
patients who underwent BS at our institution during the study period, 1016
(85.9%) were women. Thirty-nine of these women (with an average age of 31 +/- 4.8
years) became pregnant (one twin pregnancy) and 29 of the 39 had undergone a
gastric bypass. The mean time interval between BS and pregnancy was 16.6 +/- 4.8
months; however, 16 (41%) women became pregnant less than a year after BS. The
pre-BS body mass index (BMI) of the 39 women was 44.5 +/- 6.2 kg/m2 . The women
had a mean BMI of 30.2 +/- 3.8 kg/m2 when they got pregnant and they gained 13.2
+/- 7.3 kg during pregnancy. Iron deficiency was observed in 18 (46.1%) women, 16
(45.7%) had vitamin B12 deficiency, 12 (66.8%) had zinc deficiency, and 20
(60.6%) had vitamin D deficiency. Three women developed gestational diabetes
mellitus. Premature rupture of membranes occurred in two pregnancies, preterm
delivery in five, and there was one spontaneous abortion. Cesarean section was
performed in seven cases. The average newborn weight was 3002 +/- 587 g, five
were small for gestational age, and one had macrosomia. Three infants had to be
admitted to an intensive care unit. CONCLUSION: Although pregnancy after BS is
safe and well tolerated, close monitoring by a multidisciplinary team is required
to evaluate complications resulting from BS, especially a deficit of
micronutrients.
PMID- 29349845
TI - Effects of intravenous tryptophan infusion on thermoregulation in steers exposed
to acute heat stress.
AB - This study was conducted to investigate the effect of tryptophan (TRP) supply on
the thermoregulatory responses via brain serotonin (5-HT) in cattle. In period 1,
12 Holstein steers were kept under a constant room temperature (22 degrees C) and
were administered the intravenous (i.v.) infusion of saline or TRP (38.5 mg/kg/2
h). Changes in rectal temperature (RT), 5-HT concentration in the cerebrospinal
fluid (CSF), and other factors involved in thermoregulation were measured. In
period 2, the steers received the same treatments as in period 1; however, the
room temperature was elevated from 22 degrees C to 33 degrees C during i.v.
infusion and maintained at 33 degrees C for 3 h. 5-HT concentration in CSF
increased following TRP infusion in both periods, and RT significantly decreased
following TRP infusion only in period 2. The effect of TRP on respiration rate
and plasma prolactin and total triiodothyronine concentrations was not
significant. These results suggest that increase in TRP supply can attenuate
increase in RT in response to acute heat stress through the increase in brain 5
HT, followed by presumable increase in evaporative heat loss from the skin
surface in cattle. It is possible that the increase in peripheral blood TRP
metabolites could also participate in the hypothermic effect of TRP.
PMID- 29349846
TI - Preparation of dummy template-imprinted polymers for the rapid extraction of
nonsteroidal anti-inflammatory drugs residues in aquatic environmental samples.
AB - A molecularly imprinted polymer was synthesized and applied as a sorbent in the
solid-phase extraction device. The imprinted polymer was characterized by fourier
transform infrared spectroscopy and scanning electron microscope. The results
revealed that imprinted polymer possess sensitive selectivity and reliable
adsorption properties for five NSAIDs. The imprinted polymer was successfully
applied to the pre-concentration for five NSAIDs in different water samples prior
to UPLC-MS/MS. In the early studies, several factors were investigated, including
pH adjustment, the kind of elution solvent and the volume of elution solvent.
Finally, we found that the pH 5 and an aliquot of 2 mL methanol were suitable for
the water samples. The limits of detection and limits of quantitation of five
nonsteroidal anti-inflammatory drugs varied from 0.007 to 0.480 MUg L-1 and 0.03
to 1.58 MUg L-1 , respectively. The spiking recoveries of the target analytes
were 50.33-127.64% at the levels of 0.2 MUg L-1 , 2 MUg L-1 and 5 MUg L-1 . The
precision and accuracy of this method showed a great increase compared with
traditional solid-phase extraction. The developed method was successfully applied
to extraction and analysis of NSAIDs in different water samples with satisfactory
results which could help us better understand their environmental fate and risk
to ecological health.
PMID- 29349847
TI - Increased pain sensitivity in migraine and tension-type headache coexistent with
low back pain: A cross-sectional population study.
AB - BACKGROUND: Low back pain is common in the general population and in individuals
with primary headaches. We assessed the relative frequency of self-reported back
pain in persons with and without primary headaches and examined pain sensitivity.
METHOD: A population of 796 individuals completed a headache interview based on
ICHD criteria and provided data of interest in a self-administered questionnaire.
Headache cases were classified into chronic (>=15) (CH) or episodic (<15 headache
days/month) (EH). A total of 495 had a pericranial total tenderness score (TTS),
and 494 had cephalic and extracephalic pressure pain thresholds (PPTs) assessed.
RESULTS: Adjusted for age, gender, education and poor self-rated health, 1-year
relative frequency of back pain was higher in individuals with CH (82.5%) and EH
(80.1%) compared to no headache group (65.7%). In persons with back pain, TTS was
higher in CH, (26.3 +/- 12.1) than in EH, (18.5 +/- 10.0; p < 0.001) and higher
in both groups than in those with no headache, 10.8 +/- 8.5 (p < 0.001 and p <
0.001, respectively). In persons with back pain, temporalis PPT were lower in CH,
169.3 +/- 57.8, than in EH, 225.2 +/- 98.1, and in no headache group, 244.3 +/-
105.4 (p = 0.02 and p = 0.01, respectively). In persons with back pain, finger
PPT were lower in CH, 237.1 +/- 106.7, than in EH, 291.3 +/- 141.3, or in no
headache group, 304.3 +/- 137.4 (p = 0.02 and p < 0.001, respectively).
CONCLUSION: Back pain is highly frequent in individuals with CH, followed by EH
and no headache. In persons with CH, back pain is associated with lower cephalic
and extracephalic PPTs suggesting central sensitization may be a substrate or
consequence of comorbidity. SIGNIFICANCE: We found that back pain has high
relative frequency in individuals with CH followed EH and no headache. Back pain
is associated with low cephalic and extracephalic PPTs in individuals with CH.
Central sensitization may be a substrate or consequence of this comorbidity of
back pain and CH.
PMID- 29349848
TI - Evaluation of the stability and stratification of propofol and ketamine mixtures
for pediatric anesthesia.
AB - BACKGROUND: The combination of propofol and ketamine is commonly used for total
intravenous anesthesia. These drugs can be delivered in different syringes or in
the same syringe. We hypothesized that the drugs might separate and different
concentrations of each drug could be found in different parts of the syringe
during the procedure period when they were mixed in 1 syringe. METHODS: Twelve 60
mL polypropylene syringes were prepared by mixing propofol and ketamine as 4
groups on the basis of propofol/ketamine mixture ratios (5:1 and 6.7:1) and
propofol solution concentrations. Syringes were placed upright in the vertical
position into a rack and kept at room temperature (21.5-22.5 degrees C), in
daylight conditions and were not moved for 360 minutes. Samples of the mixture
were taken from both the top and the bottom of the syringe. The first 1 mL of the
samples was discarded, the following second 1 mL of the samples was filtered
using 0.2-MUm polytetrafluoroethylene filters and measured twice (n = 6). Samples
were taken at the following time intervals: T0, T10, T30, T60, T90, T120, T180,
T240, T300, and T360 min. Syringes were checked visually for any color change and
separation lines between the drugs. RESULTS: There were no significant
differences between the propofol and ketamine concentrations of the top and
bottom samples in all 4 groups. In addition, there were no statistically
significant changes of propofol and ketamine concentrations of samples over 360
minutes in any of the 4 groups. No visual changes were observed during 6 hours'
observation. CONCLUSION: The results of our measurements demonstrated that
mixtures of propofol (1% and 2%) and ketamine at 5:1 and 6.7:1 ratios could be
used in terms of mixture homogeneity and stability in a polypropylene syringe
during a 6-hour period at room temperature.
PMID- 29349849
TI - The optimal intestinal segment length for experimental size-mismatched intestinal
transplantation: Defining the maximum length with the lowest blood flow needs in
a porcine model.
AB - Transplanted Intestinal Segments (IS) must match the perfusion capacities of the
recipient. This can be challenging during a size-mismatched SBTX. In this study,
we defined the maximum IS length with lowest blood flow needs in a porcine model
by evaluating the physiological perfusion rates of different IS lengths. Blood
flow in the SMA, aorta segment four, and general circulatory parameters were
monitored before and after sequential intestinal resection. IS lengths of 30 cm,
60 cm, 120 cm, and 300 cm (n = 8 each) were compared. The IS blood flow
requirements increased with IS length (30 cm: 19.5 +/- 3.4 mL/min; 60 cm: 16.9 +/
6.7 mL/min; 120 cm: 34.9 +/- 8.5 mL/min; 300 cm: 62.9 +/- 11.6 mL/min). Absolute
IS blood flow (P = .004), percentage IS blood flow uptake from the SMA (P =
.001), and percentage IS blood flow uptake from the aorta (P = .005) increased
significantly between 60 cm and 120 cm. We concluded that 60 cm was the maximum
IS length before blood flow demands significantly increased in a porcine model.
PMID- 29349850
TI - Reconstructing geographical parthenogenesis: effects of niche differentiation and
reproductive mode on Holocene range expansion of an alpine plant.
AB - Asexual taxa often have larger ranges than their sexual progenitors, particularly
in areas affected by Pleistocene glaciations. The reasons given for this
'geographical parthenogenesis' are contentious, with expansion of the ecological
niche or colonisation advantages of uniparental reproduction assumed most
important in case of plants. Here, we parameterized a spread model for the alpine
buttercup Ranunculus kuepferi and reconstructed the joint Holocene range
expansion of its sexual and apomictic cytotype across the European Alps under
different simulation settings. We found that, rather than niche broadening or a
higher migration rate, a shift of the apomict's niche towards colder conditions
per se was crucial as it facilitated overcoming of topographical barriers, a
factor likely relevant for many alpine apomicts. More generally, our simulations
suggest potentially strong interacting effects of niche differentiation and
reproductive modes on range formation of related sexual and asexual taxa arising
from their differential sensitivity to minority cytotype disadvantage.
PMID- 29349851
TI - Clinical and molecular implications of structural changes to desmosomes and
corneodesmosomes.
AB - Desmosomes provide the main intercellular adhesive properties between epidermal
keratinocytes. Their distribution becomes uneven in severe dermatitis, multiple
allergies and metabolic wasting syndrome due to desmoglein 1 deficiency and the
loss of intercellular adhesion or acantholysis. When keratinocytes differentiate
from granular cells into cornified cells, desmosomes are transformed into
corneodesmosomes and can provide stronger intercellular adhesion. Degradation of
corneodesmosomes is a tightly regulated process involving a number of proteases
and their inhibitors. Peripheral corneodesmosomes are protected from proteolytic
degradation by the tight junction-related structures around them, and this
construction provides the basis for the normal basket weave-like structure of the
stratum corneum. In Netherton syndrome, which is caused by an absence of the
protease inhibitor lymphoepithelial Kazal-type-related inhibitor, premature
degradation of corneodesmosomes occurs due to the overactivation of proteases
involved in corneodesmosome degradation. Inflammatory peeling skin disease is
caused by the absence of corneodesmosin, a unique component of corneodesmosomes.
In this disease, corneodesmosomes are structurally abnormal, and their
adhesiveness is compromised, which leads to intercellular splitting between the
stratum corneum and stratum granulosum. The better we understand desmosome and
corneodesmosome ultrastructure in normal and diseased skin, the clearer the
physiological and pathological mechanisms of epidermal integrity become.
PMID- 29349852
TI - What really matters to people with aphasia when it comes to group work? A
qualitative investigation of factors impacting participation and integration.
AB - BACKGROUND: Participation in a group environment is an inherently complex
undertaking for people with aphasia. It involves engaging in multi-person
interactions with other people who may have a range of communication strengths
and strategies at their disposal. The potential challenges of community aphasia
group participation and practice has had limited attention in the research
literature. Evidence from group users have primarily been drawn from the
perspective of long-term members or those participating in highly specific and
time-bound groups. There is a need to explore the experiences of a broader
sample, including people who have left groups, to improve our understanding of
structures, processes as well as leadership behaviours that may facilitate
positive group participation experiences. AIM: To examine the potential factors
operating within the group environment that contribute to positive and negative
participation experiences. METHODS & PROCEDURES: Twenty-two people with aphasia
participated in semi-structured interviews about their experiences of community
aphasia groups. People who maintained long-term membership as well as those who
had left groups were sampled. An interpretative phenomenological framework was
employed to examine the data collected. OUTCOMES & RESULTS: Seven factors emerged
as central to participation experiences and contributed to the ability of people
with aphasia to integrate and engage in the group space. These factors included:
(1) balanced interactional patterns; (2) an open and non-hierarchical group
environment; (3) communication awareness and education amongst members; (4)
meaningful activity; (5) ritual and structure; (6) composition and group size;
and (7) group leadership. CONCLUSIONS & IMPLICATIONS: People with aphasia
perceive community aphasia-group participation to be beneficial to their ability
to live well with aphasia. However, a range of challenges to successful
participation are also evident. Inputs such as peer-to-peer communication
strategies, shared roles and responsibilities, and consultation with regard to
group objectives and processes provide group members with the opportunity to
become active contributors, demonstrate competence and have influence over the
group. When inputs are poorly implemented or absent, people with aphasia are at
risk of feeling disabled and marginalized by the group experience.
PMID- 29349853
TI - Piezotronic Tuning of Potential Barriers in ZnO Bicrystals.
AB - Coupling of magnetic, ferroelectric, or piezoelectric properties with charge
transport at oxide interfaces provides the option to revolutionize classical
electronics. Here, the modulation of electrostatic potential barriers at tailored
ZnO bicrystal interfaces by stress-induced piezoelectric polarization is
reported. Specimen design by epitaxial solid-state transformation allows for both
optimal polarization vector alignment and tailoring of defect states at a
semiconductor-semiconductor interface. Both quantities are probed by transmission
electron microscopy. Consequently, uniaxial compressive stress affords a complete
reduction of the potential barrier height at interfaces with head-to-head
orientation of the piezoelectric polarization vectors and an increase in
potential barrier height at interfaces with tail-to-tail orientation. The
magnitude of this coupling between mechanical input and electrical transport
opens pathways to the design of multifunctional electronic devices like strain
triggered transistors, diodes, and stress sensors with feasible applications for
human-computer interfacing.
PMID- 29349854
TI - Implementing health and social care integration in Scotland: Renegotiating new
partnerships in changing cultures of care.
AB - Health and social care integration has been a long-term goal for successive
governments in Scotland, culminating in the implementation of the recent Public
Bodies (Joint Working) Scotland Act 2014. This laid down the foundations for the
delegation of health and social care functions and resources to newly formed
Integrated Joint Boards. It put in place demands for new ways of working and
partnership planning. In this article, we explore the early implementation of
this Act and how health and social care professionals and the third sector have
begun to renegotiate their roles. The paper draws on new empirical data collated
through focus groups and interviews with over 70 professionals from across
Scotland. The data are explored through the following key themes: changing
cultures, structural imbalance, governance and partnership and the role of
individuals or "boundary spanners" in implementing change. We also draw on
evidence from other international systems of care, which have implemented
integration policies, documenting what works and what does not. We argue that
under the current framework much of the potential for integration is not being
fulfilled and that the evidence suggests that at this early stage of roll-out,
the structural and cultural policy changes that are required to enable this
policy shift have not yet emerged. Rather, integration has been left to
individual innovators or "boundary spanners" and these are acting as key drivers
of change. Where change is occurring, this is happening despite the system. As it
is currently structured, we argue that too much power is in the hands of health
and despite the rhetoric of partnership working, there are real structural
imbalances that need to be reconciled.
PMID- 29349855
TI - Understanding remote Aboriginal drug and alcohol residential rehabilitation
clients: Who attends, who leaves and who stays?
AB - INTRODUCTION AND AIMS: Aboriginal residential rehabilitation services provide
healing for Aboriginal people who misuse substances. There is limited available
research that empirically describes client characteristics of these services.
This study examined 5 years of data of a remote Aboriginal residential
rehabilitation service. DESIGN AND METHODS: Retrospective analysis of 329 client
admissions to Orana Haven Drug and Alcohol Rehabilitation Centre from 2011 to
2016. Multinomial and binary logistic regressions were conducted to identify
trends in the data. RESULTS: There were 66 admissions recorded annually, of which
most identified as Aboriginal (85%). Mean length of stay was 56 days, with one in
three (36%) discharging within the first month. A third (32%) completed, 47% self
discharged and 20% house-discharged from the program. Client age significantly
increased over time (P = 0.03), with most aged from 26 to 35. Older clients were
significantly more likely to readmit (P < 0.002) and stay longer than 90 days (P
= 0.02). Most clients were referred from the criminal justice system,
significantly increasing from 79% (2011-2012) to 96% (2015-2016) (P < 0.001) and
these clients were more likely to self-discharge (P < 0.01). Among a subset of
clients, most (69%) reported concerns with polysubstance use and half (51%)
reported mental illness. DISCUSSION AND CONCLUSIONS: The current study makes a
unique contribution to the literature by empirically describing the
characteristics of clients of a remote Aboriginal residential rehabilitation
service to more accurately tailor the service to the client's needs. Key
recommendations include integrating these empirical observations with staff and
client perceptions to co-design a model of care, standardise data collection, and
routinely following-up clients to monitor treatment effectiveness.
PMID- 29349856
TI - Self-responsibility, rationing and treatment decision making - managing moral
narratives alongside fiscal reality in the obesity surgery clinic.
AB - BACKGROUND: Addressing the prevalence of severe obesity and its concomitant
morbidities is widely acknowledged as one of the most pressing global health
priorities. Nevertheless, a paucity of effective interventions and universal
pressure on health-care budgets means that access to obesity treatments is often
limited. Although health-care rationing can be conceived as a socially
constructed process, little is known about how decisions emerge within the
context of face-to-face doctor-patient interactions. METHODS: In this study, we
used in-depth interviews and clinic observations to investigate clinicians' (n =
11) and patients' (n = 22) experiences of the rationing of obesity surgery and to
examine how broader cultural assumptions around personal responsibility for
health emerged in the context of clinical interactions. RESULTS: Patients and
clinicians worked within similar frameworks when it came to self-responsibility
for health and the appropriateness of providing publicly-funded weight loss
surgery. Issues around personal accountability dominated consultations, and
patients were expected to provide narratives of the development of their obesity
and to account for the failure of previous interventions. Clinicians faced the
added pressure of having to prioritise a limited number of patients for surgery,
which was predominantly managed through mandating pre-referral weight loss
targets. DISCUSSION: Although clinicians sought to maintain an empathic attitude
towards individual patients, in practice they were conflicted by their
responsibility to ration health-care resources and tended to rely on entrenched
models of behaviour change to allocate treatment. As a result, the content of
consultations was mostly focused on issues of personal responsibility, reflecting
wider stigmatized attitudes towards extreme obesity.
PMID- 29349858
TI - Efficient, Hysteresis-Free, and Stable Perovskite Solar Cells with ZnO as
Electron-Transport Layer: Effect of Surface Passivation.
AB - The power conversion efficiency of perovskite solar cells (PSCs) has ascended
from 3.8% to 22.1% in recent years. ZnO has been well-documented as an excellent
electron-transport material. However, the poor chemical compatibility between ZnO
and organo-metal halide perovskite makes it highly challenging to obtain highly
efficient and stable PSCs using ZnO as the electron-transport layer. It is
demonstrated in this work that the surface passivation of ZnO by a thin layer of
MgO and protonated ethanolamine (EA) readily makes ZnO as a very promising
electron-transporting material for creating hysteresis-free, efficient, and
stable PSCs. Systematic studies in this work reveal several important roles of
the modification: (i) MgO inhibits the interfacial charge recombination, and thus
enhances cell performance and stability; (ii) the protonated EA promotes the
effective electron transport from perovskite to ZnO, further fully eliminating
PSCs hysteresis; (iii) the modification makes ZnO compatible with perovskite,
nicely resolving the instability of ZnO/perovskite interface. With all these
findings, PSCs with the best efficiency up to 21.1% and no hysteresis are
successfully fabricated. PSCs stable in air for more than 300 h are achieved when
graphene is used to further encapsulate the cells.
PMID- 29349859
TI - Re: Peripartum hysterectomy: an economic analysis of direct healthcare costs
using routinely collected data: Some concerns from obstetricians' viewpoint.
PMID- 29349857
TI - A Diazido Mannose Analogue as a Chemoenzymatic Synthon for Synthesizing Di-N
acetyllegionaminic Acid-Containing Glycosides.
AB - A chemoenzymatic synthon was designed to expand the scope of the chemoenzymatic
synthesis of carbohydrates. The synthon was enzymatically converted into
carbohydrate analogues, which were readily derivatized chemically to produce the
desired targets. The strategy is demonstrated for the synthesis of glycosides
containing 7,9-di-N-acetyllegionaminic acid (Leg5,7Ac2 ), a bacterial nonulosonic
acid (NulO) analogue of sialic acid. A versatile library of alpha2-3/6-linked
Leg5,7Ac2 -glycosides was built by using chemically synthesized 2,4-diazido-2,4,6
trideoxymannose as a chemoenzymatic synthon for highly efficient one-pot
multienzyme (OPME) sialylation followed by downstream chemical conversion of the
azido groups into acetamido groups. The syntheses required 10 steps from
commercially available d-fucose and had an overall yield of 34-52 %, thus
representing a significant improvement over previous methods. Free Leg5,7Ac2
monosaccharide was also synthesized by a sialic acid aldolase-catalyzed reaction.
PMID- 29349860
TI - Effects of maternal anthropometrics on pregnancy outcomes in South Asian women: a
systematic review.
AB - AIM: This systematic review investigates associations between maternal pre
pregnancy/early-pregnancy anthropometrics (e.g. weight and body fat),
anthropometric change and pregnancy outcomes in South Asian and White women.
METHODS: Twelve electronic literature databases, reference lists and citations of
all included studies were searched. Observational studies published in the
English language were included. Descriptive synthesis was used to summarize the
evidence base. RESULTS: Twenty-two studies met the inclusion criteria (403,609
births [351,856 White and 51,753 South Asian]). Nine were prospective cohort
studies, nine were retrospective cohort studies and two were cross-sectional
studies. Results suggested that in South Asian women, maternal pre
pregnancy/early-pregnancy anthropometrics were associated with anthropometric
change, birthweight, mode of delivery and gestational diabetes mellitus (GDM).
Gestational anthropometric change was found to be associated with GDM. There was
limited evidence to suggest that there may be associations between maternal pre
anthropometrics/early anthropometrics and hypertensive disorders, stillbirth,
congenital anomalies, post-natal weight retention and post-natal impaired glucose
tolerance. The evidence suggested a combined effect of pre-pregnancy/early
pregnancy anthropometrics and gestational anthropometric change on both GDM and
post-natal weight retention. CONCLUSION: The increased risk of adverse pregnancy
outcomes in South Asian women should be considered in guidelines for weight
management before and during pregnancy.
PMID- 29349861
TI - Validated UPLC-MS/MS method for quantification of seven compounds in rat plasma
and tissues: Application to pharmacokinetic and tissue distribution studies in
rats after oral administration of extract of Eclipta prostrata L.
AB - A rapid, sensitive and specific ultra-high-performance liquid chromatography
coupled with tandem mass spectrometry (UPLC-MS/MS) method was developed to
investigate the pharmacokinetics and tissue distribution of Eclipta prostrata
extract. Rats were orally administrated the 70% ethanol extract of E. prostrata,
and their plasma as well as various organs were collected. The concentrations of
seven main compounds, ecliptasaponin IV, ecliptasaponin A, apigenin, 3'
hydroxybiochanin A, luteolin, luteolin-7-O-glucoside and wedelolactone, were
quantified by UPLC-MS/MS through multiple reactions monitoring method. The
precisions (RSD) of the analytes were all <15.00%. The extraction recoveries
ranged from 74.65 to 107.45% with RSD <= 15.36%. The matrix effects ranged from
78.00 to 118.06% with RSD <= 15.04%. To conclude, the present pharmacokinetic and
tissue distribution studies provided useful information for the clinical usage of
Eclipta prostrata L.
PMID- 29349862
TI - Implementing managed alcohol programs in hospital settings: A review of academic
and grey literature.
AB - ISSUES: People with severe alcohol use disorders are at increased risk of poor
acute-care outcomes, in part due to difficulties maintaining abstinence from
alcohol while hospitalised. Managed alcohol programs (MAP), which administer
controlled doses of beverage alcohol to prevent withdrawal and stabilise drinking
patterns, are one strategy for increasing adherence to treatment, and improving
health outcomes for hospital inpatients with severe alcohol use disorders.
APPROACH: Minimal research has examined the implementation of MAPs in hospital
settings. We conducted a scoping review to describe extant literature on MAPs in
community settings, as well as the therapeutic provision of alcohol to hospital
inpatients, to assess the feasibility of implementing formal MAPs in hospital
settings and identify knowledge gaps requiring further study. Four academic and
10 grey literature databases were searched. Evidence was synthesised using
quantitative and qualitative approaches. KEY FINDINGS: Forty-two studies met
review inclusion criteria. Twenty-eight examined the administration of alcohol to
hospital inpatients, with most reporting positive outcomes related to prevention
or treatment of alcohol withdrawal. Fourteen studies examined MAPs in the
community and reported that they help stabilise drinking patterns, reduce alcohol
related harms and facilitate non-judgemental health and social care.
IMPLICATIONS/CONCLUSIONS: MAPs in the community have been well described and
research has documented effective provision of alcohol in hospital settings for
addressing withdrawal. Implementing MAPs as a harm reduction approach in hospital
settings is potentially feasible. However, there remains a need to build off
extant literature and develop and evaluate standardised MAP protocols tailored to
acute-care settings.
PMID- 29349863
TI - Experimental Observation of Thermally Excited Triplet States of Heavier Group 15
Element Centered Diradical Dianions.
AB - One-electron reductions of Mes*As=Fl* (1; Fl*=2,7-di-tert-butylfluorenylidene,
Mes*=2,4,6-tBu3 C6 H2 ) and diarsaalkenes [1,2-b]-IF(=AsMes*)2 (2;
IF=indenofluorene) with potassium led to the isolation of the arsenic-centered
radical anion salts 1K and 2K, respectively. The diradical dianion salts 2K2 and
3K2 were afforded by the reduction of 2 and 2,8-tBu2 -[2,1-b]-IF(=AsMes*)2 (3)
with an excess amount of KC8 . The radicals have been investigated by single
crystal X-ray crystallography, EPR, and UV/Vis absorption spectroscopy, along
with theoretical calculations. The calculations revealed that 2K2 and 3K2 feature
open-shell singlet ground states with singlet-triplet energy gaps of 2.1 and 1.0
kcal mol-1 , respectively. They are readily thermally excited to triplet states
as demonstrated by EPR spectroscopy. The obtained diradicals represent the first
examples of heavier Group 15 element centered diradicals with experimentally
observable triplet states.
PMID- 29349865
TI - Superfast Room-Temperature Activation of SnO2 Thin Films via Atmospheric Plasma
Oxidation and their Application in Planar Perovskite Photovoltaics.
AB - The power conversion efficiency (PCE) of perovskite solar cells (PSCs) has now
exceeded 20%; thus, research focus has shifted to establishing the foundations
for commercialization. One of the pivotal themes is to curtail the overall
fabrication time, to reduce unit cost, and mass-produce PSCs. Additionally,
energy dissipation during the thermal annealing (TA) stage must be minimized by
realizing a genuine low-temperature (LT) process. Here, tin oxide (SnO2 ) thin
films (TFs) are formulated at extremely high speed, within 5 min, under an almost
room-temperature environment (<50 degrees C), using atmospheric Ar/O2 plasma
energy (P-SnO2 ) and are applied as an electron transport layer of a "n-i-p"-type
planar PSC. Compared with a thermally annealed SnO2 TF (T-SnO2 ), the P-SnO2 TF
yields a more even surface but also outstanding electrical conductivity with
higher electron mobility and a lower number of charge trap sites, consequently
achieving a superior PCE of 19.56% in P-SnO2 -based PSCs. These findings motivate
the use of a plasma strategy to fabricate various metal oxide TFs using the sol
gel route.
PMID- 29349866
TI - Amorphous Materials for Enhanced Localized Surface Plasmon Resonances.
AB - The discovery of localized surface plasmon resonance (LSPR) in semiconductor
nanocrystals has initiated a new field in plasmonics. Plasmonic nanocrystals in
particular have seen rapid development in recent years because they are a class
of materials with unique photoelectronic properties. At present, a growing number
of amorphous plasmonic materials has been steadily capturing scientific interest,
though only a few of these are well characterized. Here we focus on recent
developments in state-of-the art experiments and explore the vast library of
plasmonic properties in amorphous materials, including their application fields
and optical spectral range. Taken together, the growing regime of amorphous
material plasmonics offers enticing avenues for harnessing light-matter
interactions from the visible to the terahertz region, with new potential for
optical manipulation beyond what can be accomplished using traditional crystal
materials.
PMID- 29349867
TI - Volumetric modulated arc therapy treatment planning of thoracic vertebral
metastases using stereotactic body radiotherapy.
AB - PURPOSE/OBJECTIVES: To retrospectively evaluate the plan quality, treatment
efficiency, and accuracy of volumetric modulated arc therapy (VMAT) plans for
thoracic spine metastases using stereotactic body radiotherapy (SBRT).
MATERIALS/METHODS: Seven patients with thoracic vertebral metastases treated with
noncoplanar hybrid arcs (NCHA) (1 to 2 3D-conformal partial arcs +7 to 9 IMRT
beams) were re-optimized with VMAT plans using three coplanar arcs. Tumors were
located between T2 and T7 and PTVs ranged between 24.3 and 240.1 cc (median 48.1
cc). All prescriptions were 30 Gy in 5 fractions with 6 MV beams treated using
the Novalis Tx linac equipped with high definition multileaf collimators (HDMLC).
MR images were fused with planning CTs for target and OAR contouring. Plans were
compared for target coverage using conformality index (CI), homogeneity index
(HI), D90, D98, D2, and Dmedian. Normal tissue sparing was evaluated by comparing
doses to the spinal cord (Dmax, D0.35, and D1.2 cc), esophagus (Dmax and D5 cc),
heart (Dmax, D15 cc), and lung (V5 and V10). Data analysis was performed with a
two-sided t-test for each set of parameters. Dose delivery efficiency and
accuracy of each VMAT plan was assessed via quality assurance (QA) using a
MapCHECK device. The Beam-on time (BOT) was recorded, and a gamma index was used
to compare dose agreement between the planned and measured doses. RESULTS: VMAT
plans resulted in improved CI (1.02 vs. 1.36, P = 0.05), HI (0.14 vs. 0.27, P =
0.01), D98 (28.4 vs. 26.8 Gy, P = 0.03), D2 (32.9 vs. 36.0 Gy, P = 0.02), and
Dmedian (31.4 vs. 33.7 Gy, P = 0.01). D90 was improved but not statistically
significant (30.4 vs. 31.0 Gy, P = 0.38). VMAT plans showed statistically
significant improvements in normal tissue sparing: Esophagus Dmax (22.5 vs. 27.0
Gy, P = 0.03), Esophagus 5 cc (17.6 vs. 21.5 Gy, P = 0.02), and Heart Dmax (13.1
vs. 15.8 Gy, P = 0.03). Improvements were also observed in spinal cord and lung
sparing as well but were not statistically significant. The BOT showed
significant reduction for VMAT, 4.7 +/- 0.6 min vs. 7.1 +/- 1 min for NCHA (not
accounting for couch kicks). VMAT plans demonstrated an accurate dose delivery of
95.5 +/- 1.0% for clinical gamma passing rate of 3%/3 mm criteria, which was
similar to NCHA plans. CONCLUSIONS: VMAT plans have shown improved dose
distributions and normal tissue sparing compared to NCHA plans. Significant
reductions in treatment time could potentially minimize patient discomfort and
intrafraction movement errors. VMAT planning for SBRT is an attractive option for
the treatment of metastases to thoracic vertebrae, and further investigation
using alternative fractionation schedules is warranted.
PMID- 29349868
TI - Workplace alcohol harm reduction intervention in Australia: Cluster non
randomised controlled trial.
AB - INTRODUCTION AND AIMS: The workplace holds substantial potential as an alcohol
harm reduction and prevention setting. Few studies have rigorously examined
strategies to reduce workplace alcohol-related harm. Hence, an in-situ 3 year
trial of a comprehensive alcohol harm reduction intervention in Australian
manufacturing workplaces was undertaken. DESIGN AND METHODS: Informed by a gap
analysis, a multi-site trial was undertaken. Three manufacturing industry
companies, located at four separate worksites, with a minimum of 100 employees
were recruited through a local industry network. Based on worksite location, two
worksites were allocated to the intervention group and two to the comparison
group. The pre-specified primary outcome measure, risky drinking (Alcohol Use
Disorders Identification Test, AUDIT-C) and other self-report measures were
collected pre-intervention (T1), 12 months (T2) and 24 months post-intervention
(T3). RESULTS: No significant intervention effect was observed for the primary
outcome measure, risky drinking. Significant intervention effects were observed
for increased awareness of alcohol policy and employee assistance. At T3, the
odds of intervention group participants being aware of the workplace policy and
aware of employee assistance were 48.9% (95% confidence interval 29.3-88.9%) and
79.7% (11.5%, 91.8%), respectively, greater than comparison group participants.
DISCUSSION AND CONCLUSIONS: Comprehensive tailored workplace interventions can be
effective in improving workplace alcohol policy awareness. This is one of few
workplace alcohol trials undertaken to-date and the findings make an important
contribution to the limited evidence base for workplace alcohol harm prevention
initiatives.
PMID- 29349864
TI - The morphometric co-atrophy networking of schizophrenia, autistic and obsessive
spectrum disorders.
AB - By means of a novel methodology that can statistically derive patterns of co
alterations distribution from voxel-based morphological data, this study analyzes
the patterns of brain alterations of three important psychiatric spectra-that is,
schizophrenia spectrum disorder (SCZD), autistic spectrum disorder (ASD), and
obsessive-compulsive spectrum disorder (OCSD). Our analysis provides five
important results. First, in SCZD, ASD, and OCSD brain alterations do not
distribute randomly but, rather, follow network-like patterns of co-alteration.
Second, the clusters of co-altered areas form a net of alterations that can be
defined as morphometric co-alteration network or co-atrophy network (in the case
of gray matter decreases). Third, within this network certain cerebral areas can
be identified as pathoconnectivity hubs, the alteration of which is supposed to
enhance the development of neuronal abnormalities. Fourth, within the
morphometric co-atrophy network of SCZD, ASD, and OCSD, a subnetwork composed of
eleven highly connected nodes can be distinguished. This subnetwork encompasses
the anterior insulae, inferior frontal areas, left superior temporal areas, left
parahippocampal regions, left thalamus and right precentral gyri. Fifth, the co
altered areas also exhibit a normal structural covariance pattern which overlaps,
for some of these areas (like the insulae), the co-alteration pattern. These
findings reveal that, similarly to neurodegenerative diseases, psychiatric
disorders are characterized by anatomical alterations that distribute according
to connectivity constraints so as to form identifiable morphometric co-atrophy
patterns.
PMID- 29349869
TI - Clostridium difficile infection is associated with graft loss in solid organ
transplant recipients.
AB - Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea
in solid organ transplant recipients (SOT). We aimed to assess incidence, risk
factors, and outcome of CDI within the Swiss Transplant Cohort Study (STCS). We
performed a case-control study of SOT recipients in the STCS diagnosed with CDI
between May 2008 and August 2013. We matched 2 control subjects per case by age
at transplantation, sex, and transplanted organ. A multivariable analysis was
performed using conditional logistic regression to identify risk factors and
evaluate outcome of CDI. Two thousand one hundred fifty-eight SOT recipients,
comprising 87 cases of CDI and 174 matched controls were included. The overall
CDI rate per 10 000 patient days was 0.47 (95% confidence interval ([CI] 0.38
0.58), with the highest rate in lung (1.48, 95% CI 0.93-2.24). In multivariable
analysis, proven infections (hazard ratio [HR] 2.82, 95% CI 1.29-6.19) and
antibiotic treatments (HR 4.51, 95% CI 2.03-10.0) during the preceding 3 months
were independently associated with the development of CDI. Despite mild clinical
presentations, recipients acquiring CDI posttransplantation had an increased risk
of graft loss (HR 2.24, 95% CI 1.15-4.37; P = .02). These findings may help to
improve the management of SOT recipients.
PMID- 29349870
TI - Drug Dosing in Pregnant Women: Challenges and Opportunities in Using
Physiologically Based Pharmacokinetic Modeling and Simulations.
AB - The unmet medical need of providing evidence-based pharmacotherapy for pregnant
women is recognized by the regulatory bodies. Physiologically based
pharmacokinetic (PBPK) modeling offers an attractive platform to quantify
anticipated changes in the pharmacokinetics (PKs) of drugs during pregnancy.
Recent publications applying a pregnancy PBPK module to the prediction of
maternal and fetal exposure of drugs are summarized. Future opportunities to use
PBPK models to predict breast milk exposure and assess human fetotoxicity risks
are presented.
PMID- 29349871
TI - DSP30 and interleukin-2 as a mitotic stimulant in B-cell disorders including
those with a low disease burden.
AB - Chromosome abnormalities detected during cytogenetic investigations for B-cell
malignancy offer prognostic information that can have wide ranging clinical
impacts on patients. These impacts may include monitoring frequency, treatment
type, and disease staging level. The use of the synthetic oligonucleotide DSP30
combined with interleukin 2 (IL2) has been described as an effective mitotic
stimulant in B-cell disorders, not only in chronic lymphocytic leukemia (CLL) but
also in a range of other B-cell malignancies. Here, we describe the comparison of
two B-cell mitogens, lipopolysaccharide (LPS), and DSP30 combined with IL2 as
mitogens in a range of common B-cell disorders excluding CLL. The results showed
that DSP30/IL2 was an effective mitogen in mature B-cell disorders, revealing
abnormal cytogenetic results in a range of B-cell malignancies. The abnormality
rate increased when compared to the use of LPS to 64% (DSP30/IL2) from 14% (LPS).
In a number of cases the disease burden was proportionally very low, less than
10% of white cells. In 37% of these cases, the DSP30 culture revealed abnormal
results. Importantly, we also obtained abnormal conventional cytogenetics results
in 3 bone marrow cases in which immunophenotyping showed an absence of an
abnormal B-cell clone. In these cases, the cytogenetics results correlated with
the provisional diagnosis and altered their staging level. The use of DSP30 and
IL2 is recommended for use in many B-cell malignancies as an effective mitogen
and their use has been shown to enable successful culture of the malignant clone,
even at very low levels of disease.
PMID- 29349872
TI - The personal communities of men experiencing later life widowhood.
AB - Increasingly men are becoming widowed in later life due in part to a longer life
expectancy. Social networks and social support are thought to help buffer the
negative consequences of such later life transitions. This paper explores the
personal communities of a group of older men experiencing widowhood. Qualitative
in-depth interviews were conducted, September 2013-February 2014, with seven
older widowers, 71-89 years of age, in North Staffordshire, UK. Interviews
included personal community diagrams to identify the structure of the older men's
social relationships. Data analysis comprised thematic analysis of interview
transcripts and content analysis of personal community diagrams. Three
overarching themes were identified from the interview data: "Personal identity
and resilience assist transition," "Continuity in personal communities provides
stability" and "Changes in social relationships and practices facilitate
adaptation." The study identified three types of personal community among the
older widowers, comprising different combinations of family, friends and others.
The findings illustrate that some older widowers have very restricted personal
communities which puts them at greater risk of loneliness and social isolation.
The social needs of long-term carers should be addressed as isolation and
loneliness can begin long before the death of a spouse. It is important to
consider gender differences and preferences when designing interventions for
older people in order to promote engagement, social inclusion and well-being.
PMID- 29349873
TI - Carbon Molecular Sieve Membranes Derived from Troger's Base-Based Microporous
Polyimide for Gas Separation.
AB - Carbon molecular sieve (CMS)-based membranes have attracted great attention
because of their outstanding gas-separation performance. The polymer precursor is
a key point for the preparation of high-performance CMS membranes. In this work,
a microporous polyimide precursor containing a Troger's base unit was used for
the first time to prepare CMS membranes. By optimizing the pyrolysis procedure
and the soaking temperature, three TB-CMS membranes were obtained. Gas-permeation
tests revealed that the comprehensive gas-separation performance of the TB-CMS
membranes was greatly enhanced relative to that of most state-of-the-art CMS
membranes derived from polyimides reported so far.
PMID- 29349874
TI - Assessment by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass
Spectrometry of the Effects of Preanalytical Variables on Serum Peptidome
Profiles Following Long-Term Sample Storage.
AB - PURPOSE: Human serum and plasma are often used as clinical specimens in
proteomics analyses, and peptidome profiling of human serum is a promising tool
for identifying novel disease-associated biomarkers. Matrix-assisted laser
desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is widely
used for peptidomic biomarker discovery. Careful sample collection and handling
are required as either can have a profound impact on serum peptidome patterns,
yet the effects of preanalytical variables on serum peptidome profiles have not
been completely elucidated. The present study investigated the effects of
preanalytical variables, including storage temperature, duration (up to 12
months), and thawing methods, on MALDI-TOF MS-based serum peptidome patterns.
EXPERIMENTAL DESIGN: Aliquots of serum samples were pretreated with weak cation
exchanger magnetic beads using an automated ClinProtRobot system and then
analyzed by MALDI-TOF MS. RESULTS: A number of significant differences in peak
intensities were observed depending on sample processing variables. CONCLUSIONS
AND CLINICAL RELEVANCE: These peaks can be used as sample quality markers to
assess the effects of long-term storage on serum peptidome profiles using MALDI
TOF MS.
PMID- 29349875
TI - Preclinical QSP Modeling in the Pharmaceutical Industry: An IQ Consortium Survey
Examining the Current Landscape.
AB - A cross-industry survey was conducted to assess the landscape of preclinical
quantitative systems pharmacology (QSP) modeling within pharmaceutical companies.
This article presents the survey results, which provide insights on the current
state of preclinical QSP modeling in addition to future opportunities. Our
results call attention to the need for an aligned definition and consistent
terminology around QSP, yet highlight the broad applicability and benefits
preclinical QSP modeling is currently delivering.
PMID- 29349876
TI - Effectiveness of A Body Shape Index (ABSI) in predicting chronic diseases and
mortality: a systematic review and meta-analysis.
AB - Anthropometric measures are simple, inexpensive, noninvasive tools to assess the
risk of morbidity and mortality. This systematic review assessed the performance
of A Body Shape Index (ABSI) in predicting hypertension, cardiovascular disease,
type 2 diabetes and all-cause mortality and compared the differential
predictability between ABSI and two other common anthropometric measures - body
mass index and waist circumference. A keyword and reference search were conducted
in the PubMed and Web of Science for articles published until 1 November 2017.
Thirty-eight studies were included in the review, including 24 retrospective
cohort studies and 14 cross-sectional studies conducted in 15 countries. Meta
analysis found that a standard deviation increase in ABSI was associated with an
increase in the odds of hypertension by 13% and type 2 diabetes by 35% and an
increase in cardiovascular disease risk by 21% and all-cause mortality risk by
55%. ABSI outperformed body mass index and waist circumference in predicting all
cause mortality but underperformed in predicting chronic diseases. ABSI is highly
clustered around the mean with a rather small variance, making it difficult to
define a clinical cutoff for clinical practice. Future studies are warranted to
assess ABSI's potential usefulness as an anthropometric measure in population
level health surveillance.
PMID- 29349877
TI - Engineered and Laser-Processed Chitosan Biopolymers for Sustainable and
Biodegradable Triboelectric Power Generation.
AB - Recent advances achieved in triboelectric nanogenerators (TENG) focus on boosting
power generation and conversion efficiency. Nevertheless, obstacles concerning
economical and biocompatible utilization of TENGs continue to prevail. Being an
abundant natural biopolymer from marine crustacean shells, chitosan enables
exciting opportunities for low-cost, biodegradable TENG applications in related
fields. Here, the development of biodegradable and flexible TENGs based on
chitosan is presented for the first time. The physical and chemical properties of
the chitosan nanocomposites are systematically studied and engineered for
optimized triboelectric power generation, transforming the otherwise wasted
natural materials into functional energy devices. The feasibility of laser
processing of constituent materials is further explored for the first time for
engineering the TENG performance. The laser treatment of biopolymer films offers
a potentially promising scheme for surface engineering in polymer-based TENGs.
The chitosan-based TENGs present efficient energy conversion performance and
tunable biodegradation rate. Such a new class of TENGs derived from natural
biomaterials may pave the way toward the economically viable and ecologically
friendly production of flexible TENGs for self-powered nanosystems in biomedical
and environmental applications.
PMID- 29349878
TI - Efficacy of grape seed extract gel in the treatment of chronic periodontitis: A
randomized clinical study.
AB - AIM: The aim of the present study was to assess the effectiveness of applying
grape seed extract (GSE) gel in periodontal pockets for the treatment of chronic
periodontitis. METHODS: Eighty-six sites with pocket depth (PD) >4 mm were
selected from five systemically-healthy patients in whom scaling, and root
planing were performed, and oral instructions were given, a week earlier. PD,
gingival index (GI), plaque index (PI), and bleeding on probing (BOP) were
measured, and sites were then divided into the control group (N = 38) and GSE
group (N = 48). Four doses of formulated 2% mucoadhesive GSE gel were applied to
GSE group sites at baseline visit (T0), and 3, 6, and 9 days after T0. Similarly,
a control gel was applied to the control sites. PD, PI, GI and BOP were re
evaluated after 4 weeks and 6 months of first gel application. RESULTS: Paired t
test for both the control and GSE groups showed a significant reduction for all
variables after 6 months of gel application (P < .05). The independent t test
showed a significant difference (P < .05) only in the reduction of gingival index
(mean: 0.85 +/- 0.77 for control and 1.3 +/- 0.8 for GSE) and plaque index (mean:
0.75 +/- 0.71 for control and 1.12 +/- 0.7 for GSE). CONCLUSION: The subgingival
application of the formulated 2% mucoadhesive GSE gel showed significant
improvement in the PI and GI only.
PMID- 29349879
TI - A novel PKLR gene mutation identified using advanced molecular techniques.
AB - This study's purposes were to diagnose intractable hemolytic anemia and to
provide guiding treatment for the affected family members. We performed NGS in a
panel of 600 genes for blood diseases on a patient with obscure hemolytic anemia
and her parents. We confirmed the diagnosis of pyruvate kinase deficiency,
identified a novel homozygous mutation of the PKLR gene (NM_000298: exon 6:
c.T941C: p.I314T), and ruled out other blood diseases in the Chinese family.
Furthermore, amniotic fluid was taken from the mother during the second
trimester, and DNA was extracted to analyze the type of PKLR gene mutation. The
proband received cord blood and bone marrow from the second child of the mother
for hematopoietic stem cell transplantation and achieved normal hematopoiesis.
The genetic characterization analysis and genotype-phenotype correlation study of
PKLR gene suggested that NGS was an effective method to confirm the molecular
diagnosis of intractable hemolytic anemia. The identification of the mutation
aided in prenatal diagnosis in the second pregnancy and the effective clinical
management of the affected family.
PMID- 29349880
TI - Beyond the realist turn: a socio-material analysis of heart failure self-care.
AB - For patients living with chronic illnesses, self-care has been linked with
positive outcomes such as decreased hospitalisation, longer lifespan, and
improved quality of life. However, despite calls for more and better self-care
interventions, behaviour change trials have repeatedly fallen short on
demonstrating effectiveness. The literature on heart failure (HF) stands as a
case in point, and a growing body of HF studies advocate realist approaches to
self-care research and policymaking. We label this trend the 'realist turn' in HF
self-care. Realist evaluation and realist interventions emphasise that the
relationship between self-care interventions and positive health outcomes is not
fixed, but contingent on social context. This paper argues socio-materiality
offers a productive framework to expand on the idea of social context in realist
accounts of HF self-care. This study draws on 10 interviews as well as researcher
reflections from a larger study exploring health care teams for patients with
advanced HF. Leveraging insights from actor-network theory (ANT), this study
provides two rich narratives about the contextual factors that influence HF self
care. These descriptions portray not self-care contexts but self-care
assemblages, which we discuss in light of socio-materiality.
PMID- 29349881
TI - Speech and language therapists' perspectives of therapeutic alliance construction
and maintenance in aphasia rehabilitation post-stroke.
AB - BACKGROUND: Therapeutic alliance refers to the interactional and relational
processes operating during therapeutic interventions. It has been shown to be a
strong determinant of treatment efficacy in psychotherapy, and evidence is
emerging from a range of healthcare and medical disciplines to suggest that the
construct of therapeutic alliance may in fact be a variable component of
treatment outcome, engagement and satisfaction. Although this construct appears
to be highly relevant to aphasia rehabilitation, no research to date has
attempted to explore this phenomenon and thus consider its potential utility as a
mechanism for change. AIMS: To explore speech and language therapists'
perceptions and experiences of developing and maintaining therapeutic alliances
in aphasia rehabilitation post-stroke. METHODS & PROCEDURES: Twenty-two, in
depth, semi-structured interviews were conducted with speech and language
therapists working with people with aphasia post-stroke. Qualitative data were
analysed using inductive thematic analysis. OUTCOMES & RESULTS: Analysis resulted
in the emergence of three overarching themes: laying the groundwork; augmenting
cohesion; and contextual shapers. Recognizing personhood, developing shared
expectations of therapy and establishing therapeutic ownership were central to
laying the groundwork for therapeutic delivery. Augmenting cohesion was perceived
to be dependent on the therapists' responsiveness and ability to resolve both
conflict and resistance, as part of an ongoing active process. These processes
were further moulded by contextual shapers such as the patient's family,
relational continuity and organizational drivers. CONCLUSIONS & IMPLICATIONS: The
findings suggest that therapists used multiple, complex, relational strategies to
establish and manage alliances with people with aphasia, which were reliant on a
fluid interplay of verbal and non-verbal skills. The data highlight the need for
further training to support therapists to forge purposive alliances. Training
should develop: therapeutic reflexivity; inclusivity in goal setting, relational
strategies; and motivational enhancement techniques. The conceptualization of
therapeutic alliance, however, is only provisional. Further research is essential
to elucidate the experiences and perceptions of alliance development for people
with aphasia undergoing rehabilitation.
PMID- 29349882
TI - Short communication: Persistent socio-economic inequality in frequent headache
among Danish adolescents from 1991 to 2014.
AB - BACKGROUND: The association between socio-economic status (SES) and headache
among adolescents is an understudied issue, and no study has examined whether
such an association changes over time. The aim was to examine trends in socio
economic inequality in frequent headache among 11- to 15-year-olds in Denmark
from 1991 to 2014, using occupational social class (OSC) as indicator of SES.
METHODS: The study applies data from the Danish part of the international Health
Behaviour in School-aged Children (HBSC) study. HBSC includes nationally
representative samples of 11-, 13- and 15-year-olds. This study combines data
from seven data survey years from 1991 to 2014, participation rate 88.6%, n =
31,102. We report absolute inequality as per cent difference in frequent headache
between high and low OSC and relative inequality as odds ratio for frequent
headache by OSC. RESULTS: In the entire study population, 10.4% reported frequent
headache. There was a significant increase in frequent headache from 8.0% in 1991
to 12.9% in 2014, test for trend, p < 0.0001. This increasing trend was
significant in all OSCs. The prevalence of frequent headache was significantly
higher in low than high OSC, OR = 1.50 (95% CI: 1.34-1.67). This socio-economic
inequality in frequent headache was persistent from 1991 to 2014. CONCLUSION:
There was a significant and persistent socio-economic inequality, i.e. increasing
prevalence of frequent headache with decreasing OSC. The association between
socio-economic position and headache did not significantly change over time, i.e.
the statistical interaction between OSC and survey year was insignificant.
SIGNIFICANCE: The prevalence of frequent headache among adolescents increases
with decreasing SES. This socio-economic inequality has been persistent among
adolescents in Denmark from 1991 to 2014. Clinicians should be aware of this
social inequality.
PMID- 29349883
TI - Cellular cannibalism and lichen planus malignancy: A suggestive hypothesis.
PMID- 29349884
TI - Report of a human autopsy case in maxillary sinuses augmented using a synthetic
bone substitute: Micro-computed tomographic and histologic observations.
AB - OBJECTIVE: This study of a human autopsy case aimed to characterize the
histologic and micro-computed tomographic results of maxillary sinus augmentation
using a synthetic bone substitute and simultaneous implant placement at 6 years.
MATERIAL AND METHODS: This report is based on the whole-body donation of a 62
year-old male patient who died due to bladder cancer. Implants had been placed in
conjunction with sinus augmentation using a mixture of biphasic calcium phosphate
and autogenous bone into both maxillary sinuses 6 years prior to the body
donation. The maxillary sinus areas containing implants were gently removed from
the cadaver and scanned using high-resolution micro-computed tomography. Samples
were sectioned, prepared for undecalcified histologic slides and stained with
haematoxylin-eosin. RESULTS: The augmented volume was observed up to the apex of
the implants, which were successfully osseointegrated. Cross-sectional micro
computed tomographic views revealed that the bone-substitute particles were
embedded in radiopaque-mineralized tissues showing a trabecular pattern around
the implants. The histologic analysis revealed mature lamellar bone surrounding
the remaining bone-substitute particles as well as well-organized bone marrow
spaces in the augment bone area and around the dental implants. CONCLUSION: This
human autopsy study histologically confirmed the presence of successful bone
formation and long-term volume stability after sinus augmentation using biphasic
calcium phosphate and simultaneous implant placement.
PMID- 29349885
TI - A Hierarchical Z-Scheme alpha-Fe2 O3 /g-C3 N4 Hybrid for Enhanced Photocatalytic
CO2 Reduction.
AB - The challenge in the artificial photosynthesis of fossil resources from CO2 by
utilizing solar energy is to achieve stable photocatalysts with effective CO2
adsorption capacity and high charge-separation efficiency. A hierarchical direct
Z-scheme system consisting of urchin-like hematite and carbon nitride provides an
enhanced photocatalytic activity of reduction of CO2 to CO, yielding a CO
evolution rate of 27.2 umol g-1 h-1 without cocatalyst and sacrifice reagent,
which is >2.2 times higher than that produced by g-C3 N4 alone (10.3 umol g-1 h-1
). The enhanced photocatalytic activity of the Z-scheme hybrid material can be
ascribed to its unique characteristics to accelerate the reduction process,
including: (i) 3D hierarchical structure of urchin-like hematite and preferable
basic sites which promotes the CO2 adsorption, and (ii) the unique Z-scheme
feature efficiently promotes the separation of the electron-hole pairs and
enhances the reducibility of electrons in the conduction band of the g-C3 N4 .
The origin of such an obvious advantage of the hierarchical Z-scheme is not only
explained based on the experimental data but also investigated by modeling CO2
adsorption and CO adsorption on the three different atomic-scale surfaces via
density functional theory calculation. The study creates new opportunities for
hierarchical hematite and other metal-oxide-based Z-scheme system for solar fuel
generation.
PMID- 29349886
TI - Adaptation of Salmonella enterica to bile: essential role of AcrAB-mediated
efflux.
AB - Adaptation to bile is the ability to endure the lethal effects of bile salts
after growth on sublethal concentrations. Surveys of adaptation to bile in
Salmonella enterica ser. Tyhimurium reveal that active efflux is essential for
adaptation while other bacterial functions involved in bile resistance are not.
Among S. enterica mutants lacking one or more efflux systems, only strains
lacking AcrAB are unable to adapt, thus revealing an essential role for AcrAB.
Transcription of the acrAB operon is upregulated in the presence of a sublethal
concentration of sodium deoxycholate (DOC) while other efflux loci are either
weakly upregulated or irresponsive. Upregulation of acrAB transcription is strong
during exponential growth, and weak in stationary cultures. Single cell analysis
of ethidium bromide accumulation indicates that DOC-induced AcrAB-mediated efflux
occurs in both exponential and stationary cultures. Upregulation of acrAB
expression may thus be crucial at early stages of adaptation, while sustained
AcrAB activity may be sufficient to confer bile resistance in nondividing cells.
PMID- 29349887
TI - Realizing zT of 2.3 in Ge1-x-y Sbx Iny Te via Reducing the Phase-Transition
Temperature and Introducing Resonant Energy Doping.
AB - GeTe with rhombohedral-to-cubic phase transition is a promising lead-free
thermoelectric candidate. Herein, theoretical studies reveal that cubic GeTe has
superior thermoelectric behavior, which is linked to (1) the two valence bands to
enhance the electronic transport coefficients and (2) stronger enharmonic phonon
phonon interactions to ensure a lower intrinsic thermal conductivity.
Experimentally, based on Ge1-x Sbx Te with optimized carrier concentration, a
record-high figure-of-merit of 2.3 is achieved via further doping with In, which
induces the distortion of the density of states near the Fermi level. Moreover,
Sb and In codoping reduces the phase-transition temperature to extend the better
thermoelectric behavior of cubic GeTe to low temperature. Additionally,
electronic microscopy characterization demonstrates grain boundaries, a high
density of stacking faults, and nanoscale precipitates, which together with the
inevitable point defects result in a dramatically decreased thermal conductivity.
The fundamental investigation and experimental demonstration provide an important
direction for the development of high-performance Pb-free thermoelectric
materials.
PMID- 29349888
TI - Distal amyloid beta-protein fragments template amyloid assembly.
AB - Amyloid formation is associated with devastating diseases such as Alzheimer's,
Parkinson's and Type-2 diabetes. The large amyloid deposits found in patients
suffering from these diseases have remained difficult to probe by structural
means. Recent NMR models also predict heterotypic interactions from distinct
peptide fragments but limited evidence of heterotypic packed sheets is observed
in solution. Here we characterize two segments of the protein amyloid beta
(Abeta) known to form fibrils in Alzheimer's disease patients. We designed two
variants of Abeta(19-24) and Abeta(27-32), IFAEDV (I6V) and NKGAIF (N6F) to lower
the aggregation propensity of individual peptides while maintaining the similar
interactions between the two segments in their native forms. We found that the
variants do not form significant amyloid fibrils individually but a 1:1 mixture
forms abundant fibrils. Using ion mobility-mass spectrometry (IM-MS), hetero
oligomers up to decamers were found in the mixture while the individual peptides
formed primarily dimers and some tetramers consistent with a strong heterotypic
interaction between the two segments. We showed by X-ray crystallography that I6V
formed a Class 7 zipper with a weakly packed pair of beta-sheets and no
segregated dry interface, while N6F formed a more stable Class 1 zipper. In a
mixture of equimolar N6F:I6V, I6V forms a more stable zipper than in I6V alone
while no N6F or hetero-typic zippers are observed. These data are consistent with
a mechanism where N6F catalyzes assembly of I6V into a stable zipper and perhaps
into stable, pure I6V fibrils that are observed in AFM measurements.
PMID- 29349890
TI - Case report: Cytochrome P450 implications for comorbid ADHD and OCD
pharmacotherapy.
AB - TOPIC: This case report details the treatment of an early adolescent already
receiving treatment for attention-deficit hyperactivity disorder who presents
with recurrent obsessive-compulsive disorder. Potential atomoxetine (Strattera)
and fluoxetine (Prozac) interactions via Cytochrome P450 (CYP450) pathways are
examined and alternate therapies are recommended. PURPOSE: Provide a discussion
of psychopharmacogenomics, especially in the case of combining medications,
CYP450 enzymes, and clinical implications in the context of the burgeoning field
of precision medicine. The following questions are addressed: 1) What are the
recommendations for pharmacogenetics testing? 2) How should pharmacogenetics
inform medication selection? 3) What impact should CYP450 knowledge have on
medication dosing? SOURCES: Peer-reviewed journals, U.S. Health and Human
Services, National Institutes of Health, National Medical Library, and the
Clinical Pharmacology database. CONCLUSIONS: Genetic testing as a prescriptive
tool is not indicated for all medications; however, potential drug-drug
interactions, narrow therapeutic drug index, and side effect toxicity contribute
to the need for testing. An understanding of CYP450 metabolism and drug
interaction as well as metabolism phenotypes should inform prescribing and dosing
psychotropic medications.
PMID- 29349889
TI - T-cell Immunoglobulin and ITIM Domain Contributes to CD8+ T-cell
Immunosenescence.
AB - Aging is associated with immune dysfunction, especially T-cell defects, which
result in increased susceptibility to various diseases. Previous studies showed
that T cells from aged mice express multiple inhibitory receptors, providing
evidence of the relationship between T-cell exhaustion and T-cell senescence. In
this study, we showed that T-cell immunoglobulin and immunoreceptor tyrosine
based inhibitory motif (ITIM) domain (TIGIT), a novel co-inhibitory receptor, was
upregulated in CD8+ T cells of elderly adults. Aged TIGIT+ CD8+ T cells expressed
high levels of other inhibitory receptors including PD-1 and exhibited features
of exhaustion such as downregulation of the key costimulatory receptor CD28,
representative intrinsic transcriptional regulation, low production of cytokines,
and high susceptibility to apoptosis. Importantly, their functional defects
associated with aging were reversed by TIGIT knockdown. CD226 downregulation on
aged TIGIT+ CD8+ T cells is likely involved in TIGIT-mediated negative immune
suppression. Collectively, our findings indicated that TIGIT acts as a critical
immune regulator during aging, providing a strong rationale for targeting TIGIT
to improve dysfunction related to immune system aging.
PMID- 29349891
TI - Research on the preparation, uniformity and stability of mixed standard substance
for rapid detection of goat milk composition.
AB - Taking fresh goat milk as raw material after filtering, centrifuging, hollow
fiber ultrafiltration, allocating formula, value detection and preparation
processing, a set of 10 goat milk mixed standard substances was prepared on the
basis of one-factor-at-a-time using a uniform design method, and its accuracy,
uniformity and stability were evaluated by paired t-test and F-test of one-way
analysis of variance. The results showed that three milk composition contents of
these standard products were independent of each other, and the preparation using
the quasi-level design method, and without emulsifier was the best program.
Compared with detection value by cow milk standards for calibration fast
analyzer, the calibration by goat milk mixed standard was more applicable to
rapid detection of goat milk composition, detection value was more accurate and
the deviation showed less error. Single factor analysis of variance showed that
the uniformity and stability of the mixed standard substance were better; it
could be stored for 15 days at 4 degrees C. The uniformity and stability of the
in-units and inter-units could meet the requirements of the preparation of
national standard products.
PMID- 29349892
TI - 'Can the patient speak?': postcolonialism and patient involvement in
undergraduate and postgraduate medical education.
AB - CONTEXT: Patients are increasingly being engaged in providing feedback and
consultation to health care institutions, and in the training of health care
professionals. Such involvement has the potential to disrupt traditional doctor
patient power dynamics in significant ways that have not been theorised in the
medical literature. Critical theories can help us understand how power flows when
patients are engaged in the training of medical students. METHODS: This paper
applies postcolonial theory to the involvement of patients in the development and
delivery of medical education. First, I review and summarise the literature
around patient involvement in medical education. Subsequently, I highlight how
postcolonial frameworks have been applied to medical education more broadly,
extrapolating from the literature to apply a postcolonial lens to the area of
patient engagement in medical education. CONCLUSION: Concepts from postcolonial
theory can help medical educators think differently about how patients can be
engaged in the medical education project in ways that are meaningful and non
tokenistic. Specifically, the positioning of the patient as 'subaltern' can
provide channels of resistance against traditional power asymmetries. This has
curricular and methodological implications for medical education research in the
area of patient engagement.
PMID- 29349893
TI - Is overweight/obesity a risk factor for periodontitis in young adults and
adolescents?: a systematic review.
AB - BACKGROUND: Obesity in young adults and adolescents is associated with chronic co
morbidities. This project investigated whether being overweight or obese is a
risk factor for periodontitis in adolescents (13-17 years) and young adults (18
34 years). METHODS: A search of 12 databases was conducted using Medical Subject
Headings/Index and Emtree terms. Based on the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses, articles published between 2003 and 2016
were screened that reported periodontal and anthropometric measures. The
Newcastle-Ottawa Scale was used to appraise the quality of studies. RESULTS: Of
25 eligible studies from 12 countries, 17 showed an association between obesity
and periodontitis (odds ratios ranged from 1.1 to 4.5). The obesity indicators of
body mass index, waist circumference, waist-hip ratio and body fat percentage
were significantly associated with measures of periodontitis of bleeding on
probing, plaque index, probing depths, clinical attachment loss, calculus, oral
hygiene index and community periodontal index. Two prospective cohort studies in
the review showed no significant association between obesity and periodontitis,
but these studies had limitations of study design and used inappropriate
epidemiological diagnostic measures of periodontitis. CONCLUSION: There was
evidence to suggest that obesity is associated with periodontitis in adolescents
and young adults. Systematic Review Registration: PROSPERO Registration Number:
CRD42016046507.
PMID- 29349894
TI - Assessment of the potential of temporin peptides from the frog Rana temporaria
(Ranidae) as anti-diabetic agents.
AB - Temporin A (FLPLIGRVLSGIL-NH2 ), temporin F (FLPLIGKVLSGIL-NH2 ), and temporin G
(FFPVIGRILNGIL-NH2 ), first identified in skin secretions of the frog Rana
temporaria, produced concentration-dependent stimulation of insulin release from
BRIN-BD11 rat clonal beta-cells at concentrations >=1 nM, without cytotoxicity at
concentrations up to 3 MUM. Temporin A was the most effective. The mechanism of
insulinotropic action did not involve an increase in intracellular Ca2+
concentrations. Temporins B, C, E, H, and K were either inactive or only weakly
active. Temporins A, F, and G also produced a concentration-dependent stimulation
of insulin release from 1.1B4 human-derived pancreatic beta-cells, with temporin
G being the most potent and effective, and from isolated mouse islets. The data
indicate that cationicity, hydrophobicity, and the angle subtended by the charged
residues in the temporin molecule are important determinants for in vitro
insulinotropic activity. Temporin A and F (1 MUM), but not temporin G, protected
BRIN-BD11 cells against cytokine-induced apoptosis (P < 0.001) and augmented (P <
0.001) proliferation of the cells to a similar extent as glucagon-like peptide-1.
Intraperitoneal injection of temporin G (75 nmol/kg body weight) together with a
glucose load (18 mmol/kg body weight) in C57BL6 mice improved glucose tolerance
with a concomitant increase in insulin secretion whereas temporin A and F
administration was without significant effect on plasma glucose levels. The study
suggests that combination therapy involving agents developed from the temporin A
and G sequences may find application in Type 2 diabetes treatment.
PMID- 29349895
TI - Men's views and experiences of infant feeding: A qualitative systematic review.
AB - Although the advantages of breastfeeding are well documented, rates for
breastfeeding often fall short of international and national targets. Increasing
attention has been paid to the role of men in infant feeding, but a lot of the
research about men has been elicited from women, rather than from men themselves.
To explore these issues further, a systematic review of the qualitative research
on infant feeding was carried out, focusing specifically on men's own views and
experiences. Evidence was identified by searching electronic databases (CINAL,
Cochrane, PubMed, and Scopus), manually searching citations, and by searching the
grey literature. Studies were included in the review if they discussed men's
views and experiences of infant feeding and if they reported primary qualitative
data. Twenty research papers were included in the review, and each study was
summarised and then analysed thematically to produce a synthesis. Five major
analytical themes were identified: men's knowledge of infant feeding; men's
perceptions of their role in infant feeding; positive views on breastfeeding;
negative views on breastfeeding; and men's experiences of health promotion and
support. The review concludes by highlighting that although men can play an
important role in supporting women, they do not have a significant role in infant
feeding decisions.
PMID- 29349896
TI - Treatment with low doses of aspirin during chronic phase of experimental Chagas'
disease increases oesophageal nitrergic neuronal subpopulation in mice.
AB - Patients with Chagas' disease may develop dysfunctions of oesophageal and colonic
motility resulting from the degeneration or loss of the myenteric neurons of the
enteric nervous system. Studies have shown that the use of aspirin, also known as
acetylsalicylic acid (ASA), influences the pathogenesis of the disease. However,
this remains controversial. The aim of this study was to evaluate the
consequences of treatment with low doses of aspirin during the chronic phase of
Chagas' disease on oesophageal function. Twenty male Swiss mice, 60 days of age,
were used. The animals were infected with Y strain of Trypanosoma cruzi, injected
intraperitoneally. Aspirin was given at a dose of 50 mg/kg to some of the
infected animals, from the 55th to 63rd day after inoculation on consecutive
days, and from the 65th to 75th day on alternate days. We investigated food
passage of time, wall structure and nitrergic neuronal population of the distal
oesophagus. Our data revealed that the use of low doses of aspirin in chronic
Chagas' disease caused an increase in the number of nitrergic neurons and
partially prevented hypertrophy of the oesophagus. In addition, the aspirin
administration impeded Chagas' diseases associated changes in intestinal transit
time. Thus treatment with aspirin in the chronic phase of Chagas' disease changes
the natural history of the disease and raises the possibility of using it as a
new therapeutic approach to the treatment of this aspect of Chagas' disease
pathology.
PMID- 29349897
TI - Antibiogram and genetic diversity of Salmonella enterica with zoonotic potential
isolated from morbid native chickens and pigeons in Egypt.
AB - AIMS: This study investigated the possible role of Fayoumi chickens and pigeons
in the transmission of multidrug resistant (MDR) Salmonella with zoonotic
potential. METHODS AND RESULTS: Morbid Fayoumi chickens (70) and pigeons (30)
were examined to detect the prevalence and antibiotic resistance of Salmonella
and to detect and sequence sodC-1 gene as a zoonotic and phylogenetic marker.
Salmonella isolates were detected in 14.3 and 20% of the examined Fayoumi
chickens and pigeons, respectively. Salomonella subspecies salamae (43.8%) and S.
subspecies enterica serovar Bukuru (31.3%) were the most prevalent isolates. All
tested Salmonella isolates were MDR to at least five classes of antibiotics. S.
salamae and S. Bukuru isolates that carried blaTEM , qnrS, aadA2 and floR genes
expressed phenotypic resistance to cefotaxime, ciprofloxacin, streptomycin and
chloramphenicol, respectively. The aacC gene was detected in one of each S.
salamae and S. Bukuru isolate, although only the S. Bukuru isolate showed
phenotypic resistance to gentamicin. The sequence analysis of the sodC-1 gene
from Salmonella isolates showed clear inter- and intra-subspecies phylogenetic
segregation. CONCLUSIONS: Fayoumi chickens and pigeons could act as reservoirs of
MDR Salmonella. SIGNIFICANCE AND IMPACT OF THE STUDY: This study highlights the
possible emergence of Salmonella subspecies salamae with zoonotic potential.
PMID- 29349899
TI - Collaborative child home injury prevention in Thailand: An action research study.
AB - Child home accidental injury is a global health issue, and promoting child safety
is a pediatric nursing challenge worldwide. Planning child home accidental injury
prevention requires understanding of factors influencing parents' behavior.
Evidence suggests that participatory health promotion positively influences
behavior; however, research on Thai parents is limited. This qualitative, action
research study aimed to understand Thai parents' experiences of participating in
a collaborative child home accidental injury prevention program and its influence
on their behavior. Eight parental mother/father couples from one Thai province
consented to participate, providing a wide range of data via in-depth individual
interviews and self-assessment questionnaires. Thematic analysis of interview
transcripts yielded three themes: collaborative learning, parental behavior
change, and reflective learning extends beyond families. Participants reported
that workshop participation improved their child home accidental injury
prevention behavior. The present study can inform pediatric nursing, child health
care practice, and child health policy in Thailand and beyond.
PMID- 29349898
TI - Helenalin Analogues Targeting NF-kappaB p65: Thiol Reactivity and Cellular
Potency Studies of Varied Electrophiles.
AB - Helenalin is a pseudoguaianolide natural product that targets Cys38 within the
DNA binding domain of NF-kappaB transcription factor p65 (RelA). Helenalin
contains two Michael acceptors that covalently modify cysteines: a alpha
methylene-gamma-butyrolactone and a cyclopentenone. We recently reported two
simplified helenalin analogues that mimic the biological activity of helenalin
and contain both electrophilic moieties. To determine the individual
contributions of the Michael acceptors toward NF-kappaB inhibition, we
synthesized a small library of helenalin-based analogues containing various
combinations of alpha-methylene-gamma-butyrolactones and cyclopentenones. The
kinetics of thiol addition to a subset of the analogues was measured to determine
the relative thiol reactivities of the embedded electrophiles. Additionally, the
cellular NF-kappaB inhibitory activities of the analogues were determined to
elucidate the contributions of each Michael acceptor to biological potency. Our
studies suggest the alpha-methylene-gamma-butyrolactone contributes most
significantly to the NF-kappaB inhibition of our simplified helenalin analogues.
PMID- 29349900
TI - Primary cardiac angiosarcoma: A case report.
AB - Cardiac angiosarcomas are the most common primary malignant cardiac tumors in
adults. The diagnosis is often delayed due to nonspecific clinical symptoms at
presentation. The cornerstones of diagnosis are echocardiography and the
histological evaluation of the cardiac biopsy. The knowledge on the treatment is
limited; the outcomes of chemotherapy, radiotherapy, complete surgical removal,
and heart transplantation are controversial. We report a 38-year-old woman with a
primary heart tumor which infiltrated the right atrial wall and the pericardium
and caused pericardial effusion. Angiosarcoma was verified histologically. The
surgical excision could not be radical, and the patient died 3 months from
diagnosis.
PMID- 29349901
TI - Inflammatory back pain and associated disease conditions among patients with
chronic low back pain in Bangladesh.
AB - AIM: Inflammatory back pain (IBP) is the earliest symptom of axial and other
forms of spondyloarthritis (SpA). However, there are no published data on
prevalence of IBP among patients suffering from chronic low back pain (CLBP) in
Bangladesh. In this study, we estimated the prevalence of IBP and the subtypes of
SpA in a tertiary hospital in Bangladesh. METHODS: This 1 year cross-sectional
study was conducted among 240 CLBP patients in a rheumatology outpatient clinic.
Assessment of Spondyloarthritis International Society classification criteria of
IBP and predefined recognized classification criteria were followed to define
different subtypes of SpA. Means and standard deviations were reported for
continuous variables. Descriptive and bi-variate analyses were accordingly
performed. RESULTS: Of 240 CLBP patients, 60 (25%) had IBP and 180 (75%) had
mechanical back pain (MBP). Among the 60 IBP patients, 52 (86.6%) had
predominantly axial SpA (axSpA) and eight (13.4%) had predominantly peripheral
spondyloarthritis. In the axSpA group, 49 (94.2%) had radiographic axSpA (rd
axSpA) also known as AS and three (5.8%) had non-radiographic axSpA (nr-axspA).
AxSpA patients could be divided into eight (15.35%) with psoriasis, two (3.8%)
with reactive arthritis and one patient (1.9%) had arthritis associated with
inflammatory bowel disease. Fifty (83.3%) IBP and 73 (40.6%) MBP patients had age
at onset of back pain < 40 years. Forty-two (70%) of the IBP and 100 (55.6%) of
the MBP patients had normal body mass index. All these differences were
statistically significant (P <= 0.0001). CONCLUSIONS: Inflammatory back pain is
common among patients presenting with CLBP. The commonest cause of IBP is AS,
followed by PsA and nr-axSpA.
PMID- 29349902
TI - Association between pre-sarcopenia, sarcopenia, and bone mineral density in
patients with chronic hepatitis C.
AB - BACKGROUND: Preserved skeletal muscle is essential for the maintenance of healthy
bone. Loss of bone mineral density (BMD) and muscle strength, considered a
predictor of BMD, have been demonstrated in patients with cirrhosis, but they are
poorly studied in chronic hepatitis C (CHC) without cirrhosis. Thus, we aimed to
evaluate the prevalence of low BMD and its association with body composition,
muscle strength, and nutritional status in CHC. METHODS: One hundred and four
subjects [mean age, 50.5 +/- 11.3 years; 75.0% males; 67.3% non-cirrhotic; and
32.7% with compensated cirrhosis] with CHC, prospectively, underwent scanning of
the lean tissue, appendicular skeletal muscle mass (ASM), fat mass, lumbar spine,
hip, femoral neck, and whole-body BMD by dual-energy X-ray absorptiometry. Muscle
strength was assessed by dynamometry. Sarcopenia was defined by the presence of
both low, ASM/height2 (ASMI) and low muscle strength according to the European
Working Group on Sarcopenia in Older People criteria. The cut-off points for low
ASMI and low muscle strength, for women and men, were < 5.45 and < 7.26 kg/m2 and
< 20 and < 30 kg, respectively. According to the adopted World Health
Organization criteria in men aged > 50 years, the T-score of osteopenia is
between -1.0 and -2.49 standard deviation (SD) below the young average value and
of osteoporosis is >=-2.5 SD below the young normal mean for men, and the Z-score
of low bone mass is <=-2.0 SD below the expected range in men aged < 50 years and
women in the menacme. Nutritional status evaluation was based on the Controlling
Nutritional Status score. RESULTS: Low BMD, low muscle strength, pre-sarcopenia,
sarcopenia, and sarcopenic obesity were observed in 34.6% (36/104), 27.9%
(29/104), 14.4% (15/104), 8.7% (9/104), and 3.8% (4/104) of the patients,
respectively. ASMI was an independent predictor of BMD (P < 0.001). Sarcopenia
was independently associated with bone mineral content (P = 0.02) and
malnutrition (P = 0.01). In 88.9% of the sarcopenic patients and in all with
sarcopenic obesity, BMI was normal. The mid-arm muscle circumference was
positively correlated with ASMI (r = 0.88; P < 0.001). CONCLUSIONS: This is the
first study to demonstrate that ASM is an independent predictor of BMD in CHC.
Mid-arm muscle circumference coupled with handgrip strength testing should be
incorporated into routine clinical practice to detect low muscle mass, which may
be underdiagnosed when only BMI is used. These findings may influence clinical
decision-making and contribute to the development of effective strategies to
screen the musculoskeletal abnormalities in CHC patients, independently of the
stage of the liver disease.
PMID- 29349904
TI - Lysosome remodelling and adaptation during phagocyte activation.
AB - Lysosomes are acidic and hydrolytic organelles responsible for receiving and
digesting cargo acquired during endocytosis, phagocytosis, and autophagy. For
macrophages and dendritic cells, the lysosome is kingpin, playing a direct role
in microbe killing and antigen processing for presentation. Strikingly, the
historic view that lysosomes are homogeneous and static organelles is being
replaced with a more elegant paradigm, in which lysosomes are heterogeneous,
dynamic, and respond to cellular needs. For example, lysosomes are signalling
platforms that integrate stress detection and molecular decision hubs such as the
mTOR complex 1 and AMPK to modulate cellular activity. These signals can even
adjust lysosome activity by modulating transcription factors such as
transcription factor EB (TFEB) and TFE3 that govern lysosome gene expression.
Here, we review lysosome remodelling and adaptation during macrophage and
dendritic cell stimulation. First, we assess the functional outcomes and
regulatory mechanisms driving the dramatic restructuring of lysosomes from
globular organelles into a tubular network during phagocyte activation. Second,
we discuss lysosome adaptation and scaling in macrophages driven by TFEB and TFE3
stimulation in response to phagocytosis and microbe challenges. Collectively, we
are beginning to appreciate that lysosomes are dynamic and adapt to serve
phagocyte differentiation in response to microbes and immune stress.
PMID- 29349903
TI - GP73 promotes invasion and metastasis of bladder cancer by regulating the
epithelial-mesenchymal transition through the TGF-beta1/Smad2 signalling pathway.
AB - This study investigated the effects of Golgi membrane protein 73 (GP73) on the
epithelial-mesenchymal transition (EMT) and on bladder cancer cell invasion and
metastasis through the TGF-beta1/Smad2 signalling pathway. Paired bladder cancer
and adjacent tissue samples (102) and normal bladder tissue samples (106) were
obtained. Bladder cancer cell lines (T24, 5637, RT4, 253J and J82) were selected
and assigned to blank, negative control (NC), TGF-beta, thrombospondin-1 (TSP-1),
TGF-beta1+ TSP-1, GP73-siRNA-1, GP73-siRNA-2, GP73-siRNA-1+ TSP-1, GP73-siRNA-1+
pcDNA-GP73, WT1-siRNA and WT1-siRNA + GP73-siRNA-1 groups. Expressions of GP73,
TGF-beta1, Smad2, p-Smad2, E-cadherin and vimentin were detected using RT-qPCR
and Western blotting. Cell proliferation, migration and invasion were determined
using MTT assay, scratch testing and Transwell assay, respectively. Compared with
the blank and NC groups, levels of GP73, TGF-beta1, Smad2, p-Smad2, N-cadherin
and vimentin decreased, and levels of WT1 and E-cadherin increased in the GP73
siRNA-1 and GP73-siRNA-2 groups, while the opposite results were observed in the
WT1 siRNA, TGF-beta, TSP-1 and TGF-beta + TSP-1 groups. Cell proliferation,
migration and invasion notably decreased in the GP73-siRNA-1 and GP73-siRNA-2
groups in comparison with the blank and NC groups, while in the WT1 siRNA, TGF
beta, TSP-1 and TGF-beta + TSP-1 groups, cell migration, invasion and
proliferation showed the reduction after the EMT. These results suggest that GP73
promotes bladder cancer invasion and metastasis by inducing the EMT through down
regulating WT1 levels and activating the TGF-beta1/Smad2 signalling pathway.
PMID- 29349906
TI - Pregnancy greatly affects the steroidal module of the Athlete Biological
Passport.
AB - Concentrations of urinary steroids are measured in anti-doping test programs to
detect doping with endogenous steroids. These concentrations are combined into
ratios and followed over time in the steroidal module of the Athlete Biological
Passport (ABP). The most important ratio in the ABP is the
testosterone/epitestosterone (T/E) ratio but this ratio is subject to intra
individual variations, especially large in women, which complicates
interpretation. In addition, there are other factors affecting T/E. Pregnancy,
for example, is known to affect the urinary excretion rate of epitestosterone and
hence the T/E ratio. However, the extent of this variation and how pregnancy
affect other ratios has not been fully evaluated. Here we have studied the
urinary steroid profile, including 19-norandrosterone (19-NA), in 67 pregnant
women and compared to postpartum. Epitestosterone was higher and, consequently,
the T/E and 5alphaAdiol/E ratios were lower in the pregnant women.
Androsterone/etiocholanolone (A/Etio) and 5alphaAdiol/5betaAdiol, on the other
hand, were higher in the first trimester as compared to postpartum (p<0.0001 and
p=0.0396, respectively). There was no difference in A/T during pregnancy or
after. 19-NA was present in 90.5% of the urine samples collected from pregnant
women. In this study, we have shown that the steroid profile of the ABP is
affected by pregnancy, and hence can cause atypical passport findings. These
atypical findings would lead to unnecessary confirmation procedures, if the
patterns of pregnancy are not recognized by the ABP management units.
PMID- 29349905
TI - Would you like to add a weight after this blood pressure, doctor? Discovery of
potentially actionable associations between the provision of multiple screens in
primary care.
AB - RATIONALE, AIMS, AND OBJECTIVE: Guidelines recommend screening for risk factors
associated with chronic diseases but current electronic prompts have limited
effects. Our objective was to discover and rank associations between the presence
of screens to plan more efficient prompts in primary care. METHODS: Risk factors
with the greatest impact on chronic diseases are associated with blood pressure,
body mass index, waist circumference, glycaemic and lipid levels, smoking,
alcohol use, diet, and exercise. We looked for associations between the presence
of screens for these in electronic medical records. We used association rule
mining to describe relationships among items, factor analysis to find latent
categories, and Cronbach alpha to quantify consistency within latent categories.
RESULTS: Data from 92 140 patients in or around Toronto, Ontario, were included.
We found positive correlations (lift >1) between the presence of all screens. The
presence of any screen was associated with confidence greater than 80% that other
data on items with high prevalence (blood pressure, glycaemic and lipid levels,
or smoking) would also be present. A cluster of rules predicting the presence of
blood pressure were ranked highest using measures of interestingness such as
standardized lift. We found 3 latent categories using factor analysis; these were
laboratory tests, vital signs, and lifestyle factors; Cronbach alpha ranged
between .58 for lifestyle factors and .88 for laboratory tests. CONCLUSIONS:
Associations between the provision of important screens can be discovered and
ranked. Rules with promising combinations of associated screens could be used to
implement data driven alerts.
PMID- 29349907
TI - Accelerated Hydrogen Evolution Kinetics on NiFe-Layered Double Hydroxide
Electrocatalysts by Tailoring Water Dissociation Active Sites.
AB - Owing to its earth abundance, low kinetic overpotential, and superior stability,
NiFe-layered double hydroxide (NiFe-LDH) has emerged as a promising
electrocatalyst for catalyzing water splitting, especially oxygen evolution
reaction (OER), in alkaline solutions. Unfortunately, as a result of extremely
sluggish water dissociation kinetics (Volmer step), hydrogen evolution reaction
(HER) activity of the NiFe-LDH is rather poor in alkaline environment. Here a
novel strategy is demonstrated for substantially accelerating the hydrogen
evolution kinetics of the NiFe-LDH by partially substituting Fe atoms with Ru. In
a 1 m KOH solution, the as-synthesized Ru-doped NiFe-LDH nanosheets (NiFeRu-LDH)
exhibit excellent HER performance with an overpotential of 29 mV at 10 mA cm-2 ,
which is much lower than those of noble metal Pt/C and reported electrocatalysts.
Both experimental and theoretical results reveal that the introduction of Ru
atoms into NiFe-LDH can efficiently reduce energy barrier of the Volmer step,
eventually accelerating its HER kinetics. Benefitting from its outstanding HER
activity and remained excellent OER activity, the NiFeRu-LDH steadily drives an
alkaline electrolyzer with a current density of 10 mA cm-2 at a cell voltage of
1.52 V, which is much lower than the values for Pt/C-Ir/C couple and state-of-the
art overall water-splitting electrocatalysts.
PMID- 29349908
TI - Robotic-assisted coronary artery bypass surgery: an 18-year single-centre
experience.
AB - BACKGROUND: Minimally invasive robot-assisted direct coronary artery bypass
(RADCAB) has emerged as a feasible minimally invasive surgical technique for
revascularization that might offer several potential advantages over conventional
approaches. We present our 18-year experience in RADCAB. METHODS: Between
February 1998 and February 2016, 605 patients underwent RADCAB. Patients
underwent post-procedural selective graft patency assessment using cardiac
catheterization. RESULTS: The mortality rate was 0.3%. The rate of conversion to
sternotomy for any cause was reduced from 16.0% of the first 200 cases to 6.9% of
the last 405 patients. The patency rate of the LITA-to-LAD anastomosis was 97.4%.
Surgical re-exploration for bleeding occurred in 1.8% of patients, and the
transfusion rate was 9.2%. Average ICU stay was 1.2 +/- 1.4 days, and average
hospital stay was 4.8 +/- 2.9 days. CONCLUSIONS: Robot-assisted coronary artery
bypass grafting is safe, feasible and it seems to represent an effective
alternative to traditional coronary artery bypass grafting in selected patients.
PMID- 29349909
TI - A literature review and hypothesis for the etiologies of cervical and root
caries.
AB - : The presence of endogenous acids from bacteria acting on a suitable substrate
combined with sources of exogenous biocorrosives such as exogenous acids and
proteolytic enzymes in areas of stress concentration are hypothesized to lead to
the development and progression of cervical and root caries (RC). Quantifying the
effects of each of the mechanisms (stress and biocorrosion) is a daunting task to
investigate since so many factors are involved at various times in the etiology
of noncarious cervical lesions (NCCLs), cervical caries (CC), and RC. Frictional
action of the tongue has a cleansing effect and lingual serous saliva, which has
a high flow rate buffering capacity from bicarbonates seem to account for the
paucity of lingual NCCLs, cervical, and RC in these areas of teeth. Future
studies are indicated to determine the effects of stress and biocorrosion and
their factors in the etiology of CC and RC. CLINICAL SIGNIFICANCE: This
manuscript presents hypothetical and literary information that the combined
effects of stress concentration and biocorrosion contribute to the formation as
well as progression of cervical and root caries.
PMID- 29349910
TI - Accuracy of a new elastomeric impression material for complete-arch dental
implant impressions.
AB - AIM: The aim of the present study was to assess the accuracy of multi-unit dental
implant casts obtained from two elastomeric impression materials, vinyl polyether
silicone (VPES) and polyether (PE), and to test the effect of splinting of
impression copings on the accuracy of implant casts. METHODS: Forty direct
impressions of a mandibular reference model fitted with six dental implants and
multibase abutments were made using VPES and PE, and implant casts were poured (N
= 20). The VPES and PE groups were split into four subgroups of five each, based
on splinting type: (a) no splinting; (b) bite registration polyether; (c) bite
registration addition silicone; and (d) autopolymerizing acrylic resin. The
accuracy of implant-abutment replica positions was calculated on the experimental
casts, in terms of interimplant distances in the x, y, and z-axes, using a
coordinate measuring machine; values were compared with those measured on the
reference model. Data were analyzed using non-parametrical Kruskal-Wallis and
Mann-Whitney tests at alpha = .05. RESULTS: The differences between the two
impression materials, VPES and PE, regardless of splinting type, were not
statistically significant (P>.05). Non-splinting and splinting groups were also
not significantly different for both PE and VPES (P>.05). CONCLUSIONS: The
accuracy of VPES impression material seemed comparable with PE for multi-implant
abutment-level impressions. Splinting had no effect on the accuracy of implant
impressions.
PMID- 29349911
TI - Identification of fish source Vibrio alginolyticus and evaluation of its
bacterial ghosts vaccine immune effects.
AB - Vibrio alginolyticus (V. alginolyticus) is a common pathogen for humans and
marine aquatic animals. Vibriosis of marine aquatic animals, caused by V.
alginolyticus, has become more prevalent globally in recent years. Hence, a safe
and effective vaccine is urgently needed for the control of this disease. Here,
the strain 16-3 isolated from the large yellow croaker (Larimichthys crocea)
suffered from canker was identified as V. alginolyticus based on morphological,
biochemical, and 16S rDNA sequencing analysis. Then, recombinant temperature
controlled lysis plasmid pBV220-lysisE was electroporated into the strain 16-3 to
generate V. alginolyticus bacterial ghosts (VaBGs) by inducing lysis gene E
expression, and the safety and immune effects of VaBGs were further investigated
in mice and large yellow croaker. The results showed that VaBGs were as safe as
formalin-killed V. alginolyticus cells (FKC) to mice and fish. Compared with FKC
and PBS groups, significant elevations of the serum agglutinating antibody titer,
serum bactericidal activity, lymphocyte proliferative responses, and levels of
four different cytokines (Th1 type: IL-2, TNF-alpha; Th2 type: IL-4 and IL-6) in
serum were detected in the VaBGs group, indicating that a Th1/Th2-mediated mixed
immune response was elicited by the VaBGs. More importantly, after challenged
with the parent strain 16-3, VaBGs-vaccinated mice and fish showed higher
protection than FKC-vaccinated mice, the relative percent of survival (RPS) being
60%, 66.7% and 40%, respectively. Taken together, this is the first demonstration
that the newly constructed V. alginolyticus ghosts may be developed as a safe and
effective vaccine against V. alginolyticus infection in aquaculture.
PMID- 29349912
TI - Meta-analysis generates and prioritizes hypotheses for translational microbiome
research.
PMID- 29349913
TI - Eukaryotic phytoplankton community spatiotemporal dynamics as identified through
gene expression within a eutrophic estuary.
AB - Over the span of a year, we investigated the interactions between biotic and
abiotic factors within the eutrophic Neuse River Estuary (NRE). Through
metatranscriptomic sequencing in combination with water quality measurements, we
show that there are different metabolic strategies deployed along the NRE. In the
upper estuary, taxonomically resolved phytoplankton groups express more
transcripts of genes for synthesis of cellular components and carbon metabolism
whereas in the lower estuary, transcripts allocated to nutrient metabolism and
transport were more highly expressed. Metabolisms for polysaccharide synthesis
and transportation were elevated in the lower estuary and could be reflective of
unbalanced growth and/or interactions with their surrounding microbial consortia.
Our results indicate phytoplankton have high metabolic activity, suggestive of
increased growth rates in the upper estuary and display patterns reflective of
nutrient limitation in the lower estuary. Among all the environmental parameters
varying along the NRE, nitrogen availability is found to be the main driving
factor for the observed spatial divergence.
PMID- 29349914
TI - Dismal science and medicine embrace.
PMID- 29349915
TI - Surrogacy legislation remains complex and unsatisfactory.
PMID- 29349917
TI - Risk stratification for febrile neutropenia in patients with testicular germ cell
tumors.
AB - The aim of this study was to detect risk factors for febrile neutropenia (FN) in
patients with testicular germ cell tumors (TGCT). In this retrospective cohort
study at the Medical University of Graz, we included 413 consecutive TGCT
patients who received adjuvant or curative treatment with cisplatin-based
chemotherapy. FN occurred in 70 (16.9%) of 413 patients. In univariable logistic
regression, higher age (odds ratio (OR) per 5 years = 1.17, 95% CI: 1.02-1.35, P
= 0.022), reduced performance status (PS) (OR = 2.73, 1.47-5.06, P = 0.001),
seminomatous histology (OR = 2.19, 1.26-3.78, P = 0.005), poor IGCCCG risk class
(OR = 4.20, 1.71-10.33, P = 0.002), and prior radiotherapy (pRTX) (OR = 8.98,
2.09-38.61, P = 0.003) were associated with a higher risk of FN. In multivariable
analysis adjusting for age and risk classification, only poor PS (OR = 2.06, 1.05
4.03, P = 0.035), seminomatous histology (OR = 2.08, 1.01-4.26, P = 0.047), and
pRTX (OR = 7.31, 1.61-33.17, P = 0.010) prevailed. In the subgroup of seminoma
patients (n = 104), only pRTX predicted for FN risk (OR = 5.60, 1.24-25.34, P =
0.025). Five of eight seminoma patients with pRTX developed FN (63%), as compared
to 22 FN cases (23%) in the 96 seminoma patients without pRTX (P = 0.027). The
eight seminoma patients who received pRTX had significantly lower pre-chemo white
blood counts (4.7 vs. 6.5 G/L), neutrophil counts (3.2 vs. 4.3 G/L), and platelet
counts (185 vs. 272 G/L) than patients without pRTX (all P < 0.0001). TGCT
patients with a reduced performance status or who had been previously treated
with radiotherapy have an increased risk for neutropenic fever during
chemotherapy.
PMID- 29349918
TI - Dual Drug Backboned Shattering Polymeric Theranostic Nanomedicine for Synergistic
Eradication of Patient-Derived Lung Cancer.
AB - Most of the current nanoparticle-based therapeutics worldwide failing in clinical
trials face three major challenges: (i) lack of an optimum drug delivery platform
with precise composition, (ii) lack of a method of directly monitoring the fate
of a specific drug rather than using any other labelling molecules as a
compromise, and (iii) lack of reliable cancer models with high fidelity for drug
screen and evaluation. Here, starting from a PP2A inhibitor demethylcantharidin
(DMC) and cisplatin, the design of a dual sensitive dual drug backboned
shattering polymer (DDBSP) with exact composition at a fixed DMC/Pt ratio for
precise nanomedicine is shown. DDBSP self-assembled nanoparticle (DD-NP) can be
triggered intracellularly to break down in a chain-shattering manner to release
the dual drugs payload. Moreover, DD-NP with extremely high Pt heavy metal
content in the polymer chain can directly track the drug itself via Pt-based drug
mediated computer tomography and ICP-MS both in vitro and in vivo. Finally, DD-NP
is used to eradicate the tumor burden on a high-fidelity patient-derived lung
cancer model for the first time.
PMID- 29349919
TI - Analysis of Follow-Up Methods of Vascular Access and Patient Outcomes in
Hemodialysis at a Tertiary Care Hospital in China.
AB - Arteriovenous fistula is the preferred option for vascular access in hemodialysis
patients. The aim of this study was to assess different follow-up methods for
hemodialysis patients in our hemodialysis center in China. A cohort of 124
patients with stage 3 chronic kidney disease was recruited and double-blind
randomly assigned into two groups. Patients in Group A received phone calls to
schedule their next consultation a week in advance. Patients in Group B scheduled
their next appointment at the end of each visit. A total of 116 patients were
included in the study and eight dropped out. Twenty-seven patients (46.4%) in
Group A and 13 patients (22.4%) in Group B had an AVF prior to hemodialysis (P =
0.006), and 44.8% of patients in Group A and 15.5% of patients in Group B were
using AVFs at the initiation of dialysis (P = 0.003). Sixteen patients (27.6%) in
Group A and 24 patients (41.3%) in Group B required central venous catheters due
to acute on chronic kidney disease and 13 patients (22.4%) in Group A and 21
patients (36.2%) in Group B required central venous catheters due to patient
related delays (P = 0.02). At the end of the study, seven patients in Group A
died and 17 patients in Group B died (P = 0.027). The patients who received phone
calls to schedule appointments in advance had a higher rate of arteriovenous
fistulas prior to dialysis and at hemodialysis initiation had a reduced incidence
of acute on chronic kidney disease and patient-related delays, and had an
improved prognosis.
PMID- 29349920
TI - Hyperuricemia in Asian psoriatic arthritis patients.
AB - AIM: It is generally accepted that hyperuricemia is commonly associated with
psoriatic arthritis (PsA). However, variations in ethnicity, diet and habitat may
contribute to differences in prevalence and risk factors for hyperuricemia in PsA
patients. Moreover, Asian specific data is deficient. The primary objective of
the present study was to determine the prevalence of hyperuricemia among PsA
patients. The secondary objective was to explore its associated risk factors.
METHODS: This was a multi-center, cross-sectional observational study of 160 PsA
patients from local Rheumatology clinics. Serum uric acid (SUA) level and other
clinical parameters were measured and hyperuricemia was defined as SUA level
greater or equal to 360 umol/L in females and 420 umol/L in males. RESULTS: Forty
nine of 160 patients (30.6%) had hyperuricemia, of which 32 were men, 17 were
women. Among those with hyperuricemia, mean SUA level was 500.7 +/- 95.9 umol/L
and 427.8 +/- 83.1 umol/L in males and females, respectively. Univariate analysis
found: (i) overweight status; (ii) obesity; (iii) Psoriasis Area and Severity
Index; (iv) body surface area; (v) severe skin involvement, as being potentially
associated with hyperuricemia. Regression model identified overweight status
increased the likelihood of hyperuricemia in PsA, with an odds ratio of 4.4 (95%
CI: 2.0-9.5). Furthermore, there was moderately positive correlation (r = 0.37)
between body mass index (BMI) and SUA level. No associations were found between
arthritis conditions and duration, lipid profile, creatinine clearance; and
hyperuricemia. CONCLUSION: A significant proportion of PsA patients had
asymptomatic hyperuricemia. It was closely related with BMI, which represented
metabolic dysregulation; but not with severity of skin disease, joint involvement
or renal function.
PMID- 29349921
TI - Community pharmacists' views on the regulation of complementary medicines and
complementary-medicines practitioners: a qualitative study in New Zealand.
AB - OBJECTIVES: To examine community pharmacists' perspectives on CMs regulation in
New Zealand, where proposals for CMs regulations had recently been suspended and
where, currently, CMs are only weakly regulated. METHODS: Qualitative, in-depth,
semi-structured interviews with New Zealand practising community pharmacists are
identified through purposive and convenience sampling. Data were analysed using a
general inductive approach. KEY FINDINGS: Participants held mixed views regarding
harmonisation of CMs regulations across Australia and NZ; some supported an NZ
national regulatory framework for CMs, based on the Australian system.
Participants recognised the current CMs regulatory framework in NZ as inadequate,
that regulation was required to some extent, and that mandatory regulation was
not necessarily required. A key reason given in support of CMs regulations was
the need for greater assurances around quality of CMs. Participants also
supported a regulatory framework that incorporated assessment of the safety of
CMs, but were less convinced of the need for, or feasibility of, requiring
evidence of efficacy from clinical trials. Participants believed that regulation
of CMs practitioners, such as herbalists, and CMs retailers was important,
although there were mixed views as to whether regulation should be statutory or
whether self-regulation would be adequate. CONCLUSIONS: On the basis of these
findings, pharmacists would be expected to welcome proposals for national
regulations for CMs in NZ: such regulations should address concerns regarding
product quality, inappropriate health claims and supporting evidence, and
therefore should support pharmacists in meeting their obligations under the NZ
Pharmacy Council's Code of Ethics.
PMID- 29349922
TI - Association between breast milk intake at 9-10 months of age and growth and
development among Malawian young children.
AB - World Health Organization recommends exclusive breastfeeding for infants for the
first 6 months of life, followed by introduction of nutritious complementary
foods alongside breastfeeding. Breast milk remains a significant source of
nourishment in the second half of infancy and beyond; however, it is not clear
whether more breast milk is always better. The present study was designed to
determine the association between amount of breast milk intake at 9-10 months of
age and infant growth and development by 12-18 months of age. The study was
nested in a randomized controlled trial conducted in Malawi. Regression analysis
was used to determine associations between breast milk intake and growth and
development. Mean (SD) breast milk intake at 9-10 months of age was 752 (244)
g/day. Mean (SD) length-for-age z-score at 12 months and change in length-for-age
z-score between 12 and 18 months were -1.69 (1.0) and -0.17 (0.6), respectively.
At 18 months, mean (SD) expressive vocabulary score was 32 (24) words and median
(interquartile range) skills successfully performed for fine, gross, and overall
motor skills were 21 (19-22), 18 (16-19), and 38 (26-40), respectively. Breast
milk intake (g/day) was not associated with either growth or development.
Proportion of total energy intake from breast milk was negatively associated with
fine motor (beta = -0.18, p = .015) but not other developmental scores in models
adjusted for potential confounders. Among Malawian infants, neither breast milk
intake nor percent of total energy intake from breast milk at 9-10 months was
positively associated with subsequent growth between 12 and 18 months, or
development at 18 months.
PMID- 29349923
TI - Magnetic Macroporous Hydrogels as a Novel Approach for Perfused Stem Cell Culture
in 3D Scaffolds via Contactless Motion Control.
AB - There is an urgent need for 3D cell culture systems that avoid the
oversimplifications and artifacts of conventional culture in 2D. However, 3D
culture within the cavities of porous biomaterials or large 3D structures
harboring high cell numbers is limited by the needs to nurture cells and to
remove growth-limiting metabolites. To overcome the diffusion-limited transport
of such soluble factors in 3D culture, mixing can be improved by pumping,
stirring or shaking, but this in turn can lead to other problems. Using pumps
typically requires custom-made accessories that are not compatible with
conventional cell culture disposables, thus interfering with cell production
processes. Stirring or shaking allows little control over movement of scaffolds
in media. To overcome these limitations, magnetic, macroporous hydrogels that can
be moved or positioned within media in conventional cell culture tubes in a
contactless manner are presented. The cytocompatibility of the developed
biomaterial and the applied magnetic fields are verified for human hematopoietic
stem and progenitor cells (HSPCs). The potential of this technique for perfusing
3D cultures is demonstrated in a proof-of-principle study that shows that
controlled contactless movement of cell-laden magnetic hydrogels in culture media
can mimic the natural influence of differently perfused environments on HSPCs.
PMID- 29349924
TI - Parental supervision for their children's toothbrushing: Mediating effects of
planning, self-efficacy, and action control.
AB - OBJECTIVES: With 60-90% of children worldwide reportedly experiencing dental
caries, poor oral health in the younger years is a major public health issue. As
parents are important to children's oral hygiene practices, we examined the key
self-regulatory behaviours of parents for supervising their children's
toothbrushing using the health action process approach. DESIGN AND METHOD:
Participants (N = 281, 197 mothers) comprised Australian parents of 2- to 5-year
olds. A longitudinal design was used to investigate the sequential mediation
chain for the effect of intention (Time 1) on parental supervision for their
youngest child's toothbrushing (Time 3), via self-efficacy and planning (Time 2),
and action control (Time 3). RESULTS: A latent-variable structural equation
model, controlling for baseline behaviour and habit, revealed significant
indirect effects from intention via self-efficacy and action control and
intention via planning and action control, on parental supervision behaviour. The
model was a good fit to the data, explaining 74% of the variance in parents'
supervising behaviour for their children's toothbrushing. CONCLUSION: While
national recommendations are provided to guide parents in promoting good oral
hygiene practices with their children, current results show the importance of
going beyond simple knowledge transmission to support parents' intentions to
supervise their children's toothbrushing actually materialize. Current findings
make a significant contribution to the cumulative empirical evidence regarding
self-regulatory components in health behaviour change and can inform intervention
development to increase parents' participation in childhood oral hygiene
practices, thus helping to curb rising oral health conditions and diseases.
Statement of contribution What is already known on this subject? Self-regulatory
skills are important to translate intentions into behaviour. Self-efficacy,
planning, and action control are key self-regulatory skills for behaviour change.
What does this study add? Self-regulatory skills are needed for parents to
supervise their children's toothbrushings. Self-efficacy, planning, and action
control are important self-regulatory skills in this context. Future
interventions should map these self-regulatory predictors onto behaviour change
techniques.
PMID- 29349926
TI - Extracellular vesicles from early stage Plasmodium falciparum-infected red blood
cells contain PfEMP1 and induce transcriptional changes in human monocytes.
AB - Pathogens can release extracellular vesicles (EVs) for cell-cell communication
and host modulation. EVs from Plasmodium falciparum, the deadliest malaria
parasite species, can transfer drug resistance genes between parasites. EVs from
late-stage parasite-infected RBC (iRBC-EVs) are immunostimulatory and affect
endothelial cell permeability, but little is known about EVs from early stage
iRBC. We detected the parasite virulence factor PfEMP1, which is responsible for
iRBC adherence and a major contributor to disease severity, in EVs, only up to 12
hr post-RBC invasion. Furthermore, using PfEMP1 transport knockout parasites, we
determined that EVs originated from inside the iRBC rather than the iRBC surface.
Proteomic analysis detected 101 parasite and 178 human proteins in iRBC-EVs.
Primary human monocytes stimulated with iRBC-EVs released low levels of
inflammatory cytokines and showed transcriptomic changes. Stimulation with iRBC
EVs from PfEMP1 knockout parasites induced more gene expression changes and
affected pathways involved in defence response, stress response, and response to
cytokines, suggesting a novel function of PfEMP1 when present in EVs. We show for
the first time the presence of PfEMP1 in early stage P. falciparum iRBC-EVs and
the effects of these EVs on primary human monocytes, uncovering a new mechanism
of potential parasite pathogenesis and host interaction.
PMID- 29349925
TI - Ethanolamine is a valuable nutrient source that impacts Clostridium difficile
pathogenesis.
AB - Clostridium (Clostridioides) difficile is a gastrointestinal pathogen that
colonizes the intestinal tract of mammals and can cause severe diarrheal disease.
Although C. difficile growth is confined to the intestinal tract, our
understanding of the specific metabolites and host factors that are important for
the growth of the bacterium is limited. In other enteric pathogens, the membrane
derived metabolite, ethanolamine (EA), is utilized as a nutrient source and can
function as a signal to initiate the production of virulence factors. In this
study, we investigated the effects of ethanolamine and the role of the predicted
ethanolamine gene cluster (CD1907-CD1925) on C. difficile growth. Using targeted
mutagenesis, we disrupted genes within the eut cluster and assessed their roles
in ethanolamine utilization, and the impact of eut disruption on the outcome of
infection in a hamster model of disease. Our results indicate that the eut gene
cluster is required for the growth of C. difficile on ethanolamine as a primary
nutrient source. Further, the inability to utilize ethanolamine resulted in
greater virulence and a shorter time to morbidity in the animal model. Overall,
these data suggest that ethanolamine is an important nutrient source within the
host and that, in contrast to other intestinal pathogens, the metabolism of
ethanolamine by C. difficile can delay the onset of disease.
PMID- 29349927
TI - Treatment-related toxicities of immune checkpoint inhibitors in advanced cancers:
A meta-analysis.
AB - BACKGROUND: We performed a meta-analysis to quantify toxic death, adverse events
(AEs) and treatment discontinuation due to AEs from checkpoint inhibitors (CI).
METHODS: We searched for randomized trials with adequate reporting for toxicity
outcomes. Pooled risk ratios were estimated for CI versus chemotherapy or
different combinations of these agents. RESULTS: Twenty trials of five different
cancers with 10 794 patients with performance status 0 or 1 were identified.
Toxic deaths from CI were infrequent (0.6%). Treatment discontinuations were less
frequent for programmed-death-1 (PD-1) or PD-ligand-1 (PD-L1) inhibitors (5.8% vs
13.3%, P < 0.001) and cytotoxic-T-lymphocyte-associated-antigen-4 (CTLA-4)
inhibitors (6.2% vs 11.4%, P = 0.002) than chemotherapy. PD-1/PD-L1 inhibitors
had less grade 3, 4, and 5 (G3/4/5) AEs than chemotherapy (13.8% vs 39.8%, P <
0.001) or CTLA-4 inhibitors (13.4% vs 22.8%, P < 0.001). Combination CI had
higher discontinuation (37.8% vs 11.6%, P < 0.001) and higher G3/4/5 AEs (55.3%
vs 21.9%, P < 0.001) than CI monotherapy. Endocrinopathy (11.2% vs 0.9%), rash
(10.1% vs 4.3%) and pneumonitis (3.1% vs 0.7%) were associated with CI, and
alopecia (25.9% vs 1.0%), neutropenia (16.6% vs 0.6%) and neuropathy (7.6% vs
3.0%) with chemotherapy. CONCLUSIONS: CI inhibitors have different toxicity
profiles to chemotherapy. These findings are useful for patient counselling and
planning of future trials.
PMID- 29349928
TI - Problem behaviours and psychotropic medication use in intellectual disability: a
multinational cross-sectional survey.
AB - BACKGROUND: Problem behaviours (PBs) are a common cause for clinician contact in
people with disorders of intellectual development and may be a common cause for
the prescription of psychotropic medication. We aimed to use a large,
multinational sample to define the prevalence of PBs, the associations with
psychotropic medication use, and to assess for any potential 'diagnostic
overshadowing' by the label of PBs in a population of people with disorders of
intellectual development. METHOD: A multinational, multi-setting, cross-sectional
service evaluation and baseline audit was completed. Data were collected from UK
hospitals, UK community settings, Sri Lanka and Hong Kong. A semi-structured
questionnaire was completed by treating clinicians, capturing demographic
details, prevalence rates of intellectual disability and psychotropic medication
use, alongside psychiatric co-morbidity. RESULTS: A sample size of 358 was
obtained, with 65% of included participants treated in an inpatient setting.
Psychotropic use was prevalent (90%) in our sample, particularly antipsychotics
(74%). The prevalence of PB was high (83%). There was no statistically
significant association between psychotropic prescription and recorded
psychiatric co-morbidity, suggesting prevalent 'off-label' use for PBs, or poor
recording of psychiatric co-morbidity. There was some evidence of possible
diagnostic overshadowing due to the PB classification. A higher dose of
psychotropic medication was associated with aggression toward others (P = 0.03).
CONCLUSIONS: We found evidence of prevalent potential 'off-label' use for
psychotropic medication, which may be due to PBs. We also found evidence of
potential diagnostic-overshadowing, where symptoms of psychiatric co-morbidity
may have been attributed to PBs. Our findings provide renewed importance, across
borders and health systems, for clinicians to consider a holistic approach to
treating PBs, and attempting to best understand the precipitants and predisposing
factors before psychotropic prescribing.
PMID- 29349930
TI - Upcoming events of interest.
PMID- 29349929
TI - Severity of cognitive disability and mental health court determinations about
fitness to stand trial.
AB - BACKGROUND: Little is known about the socio-demographic, clinical and legal
determinants of mental health court decisions of unsoundness of mind and
unfitness to stand trial for people with cognitive disability. We aimed to
estimate the association between severity of cognitive disability and mental
health court determinations of unsoundness or unfitness and describe the socio
demographic, clinical and legal factors that predict these determinations.
METHODS: Case file data were extracted on 92 individuals who had a criminal case
referred to the Queensland Mental Health Court between 1 January 2013 and 31
December 2014 due to cognitive disability. We fit a modified multivariable
Poisson regression model to estimate the association between severity of
cognitive impairment and mental health court determination, controlling for socio
demographic, clinical and legal factors. RESULTS: Adjusting for covariate
effects, severity of cognitive impairment was positively associated with being
found unfit to stand trial (adjusted prevalence risk ratio = 1.57; 95% confidence
interval: 1.07, 2.33; P = 0.023), and comorbid psychotic disorder predicted an
increased risk of being found unsound of mind at the time of offence (adjusted
prevalence risk ratio = 3.63; 95% confidence interval: 1.38, 9.54; P = 0.009) by
the Queensland Mental Health Court. CONCLUSIONS: Severity of cognitive disability
is associated with determinations of unfitness but does not predict
determinations of unsoundness in the Queensland Mental Health Court. Psychiatric
assessments of cognitive impairment play a pivotal role in mental health court
determinations for people with cognitive disability.
PMID- 29349931
TI - Biomimetic Architectures for Peripheral Nerve Repair: A Review of Biofabrication
Strategies.
AB - Biofabrication techniques have endeavored to improve the regeneration of the
peripheral nervous system (PNS), but nothing has surpassed the performance of
current clinical practices. However, these current approaches have intrinsic
limitations that compromise patient care. The "gold standard" autograft provides
the best outcomes but requires suitable donor material, while implantable hollow
nerve guide conduits (NGCs) can only repair small nerve defects. This review
places emphasis on approaches that create structural cues within a hollow NGC
lumen in order to match or exceed the regenerative performance of the autograft.
An overview of the PNS and nerve regeneration is provided. This is followed by an
assessment of reported devices, divided into three major categories: isotropic
hydrogel fillers, acting as unstructured interluminal support for regenerating
nerves; fibrous interluminal fillers, presenting neurites with topographical
guidance within the lumen; and patterned interluminal scaffolds, providing 3D
support for nerve growth via structures that mimic native PNS tissue. Also
presented is a critical framework to evaluate the impact of reported outcomes.
While a universal and versatile nerve repair strategy remains elusive, outlined
here is a roadmap of past, present, and emerging fabrication techniques to inform
and motivate new developments in the field of peripheral nerve regeneration.
PMID- 29349932
TI - Isolation and characterization of lectin with antibacterial, antibiofilm and
antiproliferative activities from Acinetobacter baumannii of environmental
origin.
AB - AIMS: Lectin is a nonimmunogenic glycoprotein that has been extracted mostly from
the primary plant source leguminoase. Its ability to precisely recognize and bind
to the complex cell bound structure enables it to play diverse roles. In this
study, we obligate to define new sources of lectins since the production of
lectins is very expensive. Therefore, we performed a study with the goal to
isolate and characterize lectin from bacteria of plant origin and screen its
ability as an antibacterial, antibiofilm and antiproliferative agent. METHODS AND
RESULTS: We investigated isolates of environmental origin for their ability to
produce lectin using phenotypic and molecular detection. The lectin was purified
from an isolate AB119 which has abundant lectin activity and its molecular weight
was determined by SDS-PAGE and HPLC. This lectin has a molecular weight of 30 kD
and used to evaluate its antimicrobial, antibiofilm and antiproliferative
activities using earlier published protocols. All bacterial isolates tested in
this study showed the ability to produce biofilm which was inhibited in the
presence of lectin significantly. In microtitre plate assay, the scale of biofilm
inhibition by the purified lectin was significantly reduced for all bacterial
species. Lectin inhibited the growth of all three tested bacterial species after
treatment for 24 h and this antimicrobial effect was uniform to all species
irrespective of Gram positive or Gram negative. The antiproliferative effects of
lectin against HeLa cells were determined using MTT assay showed significant
inhibitory effects on the proliferation at an IC50 of 10 MUM for 24 h.
CONCLUSION: This study concludes that lectin has a promising application as an
antimicrobial and, antibiofilm agent to control multidrug-resistant pathogen
associated infections. At the same time, it has also promising ability to control
the proliferation of tumour cell as evident by our study results. SIGNIFICANCE
AND IMPACT OF STUDY: AB119 lectin from A.baumannii species was verified for its
capability to control microbial growth and its biofilm formation. Results showed
lectin was able to reduce growth as well biofilm formation of both Gram-positive
and Gram-negative bacterial species. Lectin has a promising application as an
antibiofilm agent to combat the growing number of multidrug-resistant pathogen
associated infections.
PMID- 29349933
TI - Patient's specific integration of OAR doses (D2 cc) from EBRT and 3D image-guided
brachytherapy for cervical cancer.
AB - The objective of this study was to assess the recommended DVH parameter (e.g., D2
cc) addition method used for combining EBRT and HDR plans, against a reference
dataset generated from an EQD2-based DVH addition method. A revised DVH parameter
addition method using EBRT DVH parameters derived from each patient's plan was
proposed and also compared with the reference dataset. Thirty-one biopsy-proven
cervical cancer patients who received EBRT and HDR brachytherapy were
retrospectively analyzed. A parametrial and/or paraaortic EBRT boost were
clinically performed on 13 patients. Ten IMRT and 21 3DCRT plans were determined.
Two different HDR techniques for each HDR plan were analyzed. Overall D2 cc and
D0.1 cc OAR doses in EQD2 were statistically analyzed for three different DVH
parameter addition methods: a currently recommended method, a proposed revised
method, and a reference DVH addition method. The overall D2 ccEQD2 values for all
rectum, bladder, and sigmoid for a conformal, volume optimization HDR plan
generated using the current DVH parameter addition method were significantly
underestimated on average -5 to -8% when compared to the values obtained from the
reference DVH addition technique (P < 0.01). The revised DVH parameter addition
method did not present statistical differences with the reference technique (P >
0.099). When PM boosts were considered, there was an even greater average
underestimation of -8~-10% for overall OAR doses of conformal HDR plans when
using the current DVH parameter addition technique as compared to the revised DVH
parameter addition. No statistically significant differences were found between
the 3DCRT and IMRT techniques (P > 0.3148). It is recommended that the overall D2
cc EBRT doses are obtained from each patient's EBRT plan.
PMID- 29349934
TI - Interleukin-34 levels in gingival crevicular fluid and plasma in periodontal
health and disease with and without type-2 diabetes mellitus.
AB - AIM: The aim of the present study was to evaluate and correlate the levels of
interleukin-34 (IL-34) in gingival crevicular fluid (GCF) and plasma in chronic
periodontitis (CP) patients with and without type-2 diabetes mellitus (DM).
METHODS: A total of 175 patients were divided into five groups: (a) group I had
35 periodontally-healthy patients; (b) group II had 35 chronic gingivitis
patients; (c) group III had 35 CP patients without type-2 DM; (d) group IV had 35
CP patients with type-2 DM; and (e) group V had 35 type-2 DM patients without CP.
The GCF and plasma levels of IL-34 were quantified using enzyme-linked
immunosorbent assay. Clinical and systemic parameters, such as gingival index,
probing pocket depth, clinical attachment loss, and glycated hemoglobin levels,
were evaluated. RESULTS: The mean IL-34 concentration in GCF and plasma was
highest for group IV, followed by groups III, V, and II, and lowest in group I.
The difference between them was statistically significant (P < .05). There was a
positive correlation between IL-34 concentration in GCF and plasma in the study
groups, with the exception of group I, for which there was a negative
correlation. CONCLUSION: IL-34 can be considered a possible GCF and plasma
inflammatory biomarker of periodontal disease progression and DM.
PMID- 29349936
TI - Preeclampsia Increases the Incidence of Postpartum Cerebrovascular Disease in
Korean Population.
AB - BACKGROUND: Multiple studies have been reported regarding preeclampsia as a
possible risk factor of cerebrovascular disease (CVD). However, the correlation
of preeclampsia and CVD, whether it is a cause-effect relationship or they are
sharing common predisposing condition, is not well understood. Therefore, the aim
of this study was to investigate the association between the preeclampsia during
pregnancy and development of postpartum CVD. METHODS: A total of 1,384,550 Korean
women who had a delivery between January 1, 2010 and December 31, 2012, were
enrolled. Women with the risk of CVD within 1 year prior to pregnancy were
excluded based on the Charlson comorbidity index. Primary endpoint was the event
of CVD within a year from delivery. After exclusion, 1,075,061 women were
analyzed. RESULTS: During the follow-up of 1 year postpartum, there were 25,577
preeclampsia out of 1,072,041 women without postpartum CVD (2.39%), and 121 of
3,020 women with postpartum CVD had preeclampsia before delivery (4.01%). In
multivariate logistic regression analysis, women who had preeclampsia during
pregnancy showed a higher risk for postpartum CVD (odds ratio, 1.64; 95%
confidence interval, 1.37-1.98). CONCLUSION: The incidence of CVD after delivery
was higher in women who had preeclampsia during pregnancy.
PMID- 29349935
TI - Pitfalls in the measurement of muscle mass: a need for a reference standard.
AB - BACKGROUND: All proposed definitions of sarcopenia include the measurement of
muscle mass, but the techniques and threshold values used vary. Indeed, the
literature does not establish consensus on the best technique for measuring lean
body mass. Thus, the objective measurement of sarcopenia is hampered by
limitations intrinsic to assessment tools. The aim of this study was to review
the methods to assess muscle mass and to reach consensus on the development of a
reference standard. METHODS: Literature reviews were performed by members of the
European Society for Clinical and Economic Aspects of Osteoporosis and
Osteoarthritis working group on frailty and sarcopenia. Face-to-face meetings
were organized for the whole group to make amendments and discuss further
recommendations. RESULTS: A wide range of techniques can be used to assess muscle
mass. Cost, availability, and ease of use can determine whether the techniques
are better suited to clinical practice or are more useful for research. No one
technique subserves all requirements but dual energy X-ray absorptiometry could
be considered as a reference standard (but not a gold standard) for measuring
muscle lean body mass. CONCLUSIONS: Based on the feasibility, accuracy, safety,
and low cost, dual energy X-ray absorptiometry can be considered as the reference
standard for measuring muscle mass.
PMID- 29349937
TI - Changes in Clinical Characteristics of Patients with an Initial Diagnosis of
Prostate Cancer in Korea: 10-Year Trends Reported by a Tertiary Center.
AB - BACKGROUND: The Korea Central Cancer Registry reported that incidence rates of
prostate cancer have not increased continuously. We used recent trends in the
incidence of prostate cancer to generate a preliminary report of the Korean
population with prostate cancer. METHODS: Patients initially diagnosed with
prostate cancer by prostate biopsy from 2006 to 2015 at our tertiary center were
selected. All patients were categorized according to age (< 65, 65-75, > 75
years), time period (2006-2010 vs. 2011-2015), and risk classification. Patients
with insufficient data were excluded from the analysis. RESULTS: Of 675 patients
(median prostate-specific antigen [PSA], 9.09 ng/mL), those with a Gleason score
(GS) of 6 (32.3%) comprised the largest proportion in our cohort. The proportion
with a GS of 8 increased for those aged 65-75 years, despite the lack of increase
in PSA. Treatment patterns changed for those with very low to low risk cancer.
The overall survival (OS) rate and the cancer-specific survival (CSS) rate for
all patients at 5 years were 87% and 90%, respectively. Patients with a low body
mass index (BMI; <= 23 kg/m2) had worse median OS and CSS rates. CONCLUSION:
Significant differences in risk classifications and initial treatments were found
between 2006-2010 and 2011-2015. Although PSA did not change, the GS did change.
Lower BMI (<= 23 kg/m2) had worse effects on OS and CSS rates for Korean prostate
cancer patients.
PMID- 29349938
TI - Improved Regional Disparities in Neonatal Care by Government-led Policies in
Korea.
AB - BACKGROUND: Although the number of high-risk neonates has increased in Korea,
hospitals were reluctant to open or maintain neonatal intensive care unit (NICU)
due to the low medical cost. Consequently, there were regional disparities in
facilities, equipment, and neonatal health outcomes. For these reasons, the
Korean government began to invest in neonatal care during the last decade. We
identified the status of NICUs in Korea and assessed changes after the government
driven policies. METHODS: We surveyed 87 of 89 hospitals that operated NICUs in
2015. The questionnaire assessed the number of NICU beds, admission and mortality
rates of very low birthweight infants (VLBWIs), personnel status, equipment and
facilities, and available multidisciplinary approach. Current data was compared
with the previous studies and changes in the status and function of the
nationwide NICU from 2009 and 2011. RESULTS: During the last 7 years, there was
an increase of 462 NICU beds, which met the required number estimated by the
number of births and covered about 90% of regional VLBWI births. Status of
facilities and equipment improved in all regions in Korea but there were still
regional differences in multidisciplinary approach and human resources. The
difference in odds ratios for mortality of VLBWI between regions decreased
compared to 2009. CONCLUSION: There was improvement in regional disparities of
neonatal care and mortality of premature babies with the government investment in
Korea. Further supports are required for human resources and referral system.
PMID- 29349939
TI - Comparison of District-level Smoking Prevalence and Their Income Gaps from Two
National Databases: the National Health Screening Database and the Community
Health Survey in Korea, 2009-2014.
AB - BACKGROUND: We compared age-standardized prevalence of cigarette smoking and
their income gaps at the district-level in Korea using the National Health
Screening Database (NHSD) and the Community Health Survey (CHS). METHODS: Between
2009 and 2014, 39,049,485 subjects participating in the NHSD and 989,292
participants in the CHS were analyzed. The age-standardized prevalence of smoking
and their interquintile income differences were calculated for 245 districts of
Korea. We examined between-period correlations for the age-standardized smoking
prevalence at the district-level and investigated the district-level differences
in smoking prevalence and income gaps between the two databases. RESULTS: The
between-period correlation coefficients of smoking prevalence for both genders
were 0.92-0.97 in NHSD and 0.58-0.69 in CHS, respectively. When using NHSD, we
found significant income gaps in all districts for men and 244 districts for
women. However, when CHS was analyzed, only 167 and 173 districts for men and
women, respectively, showed significant income gaps. While correlation
coefficients of district-level smoking prevalence from two databases were 0.87
for men and 0.85 for women, a relatively weak correlation between income gaps
from the two databases was found. CONCLUSION: Based on two databases, income gaps
in smoking prevalence were evident for nearly all districts of Korea. Because of
the large sample size for each district, NHSD may provide stable district-level
smoking prevalence and its income gap and thus should be considered as a valuable
data source for monitoring district-level smoking prevalence and its
socioeconomic inequality.
PMID- 29349941
TI - Letter to the Editor: When Claiming a U-shaped Association between Uric Acid
Levels and Major Adverse Cardiac Events, Perhaps Show the Evidence?
PMID- 29349940
TI - Etiology of Invasive Bacterial Infections in Immunocompetent Children in Korea
(2006-2010): a Retrospective Multicenter Study.
AB - BACKGROUND: Invasive bacterial infections in apparently immunocompetent children
were retrospectively analyzed to figure causative bacterial organisms in Korea.
METHODS: A total of 947 cases from 25 university hospitals were identified from
2006 to 2010 as a continuance of a previous 10-year period study from 1996 to
2005. RESULTS: Escherichia coli (41.3%), Streptococcus agalactiae (27.7%), and
Staphylococcus aureus (27.1%) were the most common pathogens in infants < 3
months of age. S. agalactiae was the most prevalent cause of meningitis and
pneumonia and E. coli was the major cause of bacteremia without localizing signs
in this group. In children 3 to 59 months of age, Streptococcus pneumoniae
(54.2%), S. aureus (20.5%), and Salmonella spp. (14.4%) were the most common
pathogens. S. pneumoniae was the leading cause of pneumonia (86.0%), meningitis
(65.0%), and bacteremia without localizing signs (49.0%) in this group. In
children >= 5 years of age, S. aureus (62.8%) was the predominant pathogen,
followed by Salmonella species (12.4%) and S. pneumoniae (11.5%). Salmonella
species (43.0%) was the most common cause of bacteremia without localizing signs
in this group. The relative proportion of S. aureus increased significantly over
the 15-year period (1996-2010) in children >= 3 months of age (P < 0.001), while
that of Haemophilus influenzae decreased significantly in both < 3 months of age
group (P = 0.036) and >= 3 months of age groups (P < 0.001). CONCLUSION: S.
agalactiae, E. coli, S. pneumoniae, and S. aureus are common etiologic agents of
invasive bacterial infections in Korean children.
PMID- 29349942
TI - Ancient Soil-Transmitted Parasite Eggs Detected from the Sixth Century Three
Kingdom Period Silla Tomb.
AB - The parasitic infection patterns of the Joseon period have begun to be revealed
in a series of paleoparasitological studies. However, parasitism prevailing
during or before the Three Kingdom period is still relatively unexplored. In the
present study, we therefore conducted parasitological examinations of soil and
organic-material sediments precipitated upon human hipbone and sacrum discovered
inside an ancient Mokgwakmyo tomb dating to the Silla Dynasty (57 BCE-660 CE).
Within the samples, we discovered ancient Ascaris lumbricoides (eggs per gram
[EPG], 46.6-48.3) and Trichuris trichiura (EPG, 32.8-62.1) eggs, the species
commonly detected among Korean populations until just prior to the 1970s. These
findings show that soil-transmitted parasitic infection among the Silla nobility
might not have been uncommon. This is the first-ever report on the presence of
ancient parasite eggs in the samples obtained from a Three Kingdom period tomb;
and it also presents the earliest positive results for any of the ancient South
Korean tombs paleoparasitologically examined to date.
PMID- 29349943
TI - Environmental and Body Concentrations of Heavy Metals at Sites Near and Distant
from Industrial Complexes in Ulsan, Korea.
AB - BACKGROUND: Industrial pollution may affect the heavy metal body burden of people
living near industrial complexes. We determined the average concentrations of
atmospheric heavy metals in areas close to and distant from industrial complexes
in Korea, and the body concentrations of these heavy metals in residents living
near and distant from these facilities. METHODS: The atmospheric data of heavy
metals (lead and cadmium) were from the Regional Air Monitoring Network in Ulsan.
We recruited 1,148 participants, 872 who lived near an industrial complex
("exposed" group) and 276 who lived distant from industrial complexes ("non
exposed" group), and measured their concentrations of blood lead, urinary
cadmium, and urinary total mercury. RESULTS: The results showed that atmospheric
and human concentrations of heavy metals were higher in areas near industrial
complexes. In addition, residents living near industrial complexes had higher
individual and combined concentrations (cadmium + lead + mercury) of heavy
metals. CONCLUSION: We conclude that residents living near industrial complexes
are exposed to high concentrations of heavy metals, and should be carefully
monitored.
PMID- 29349944
TI - Investigation of Clinical and Pathological Relationships between Adult- and
Pediatric-type NASH in Korean Children.
AB - BACKGROUND: Histologically, nonalcoholic steatohepatitis (NASH) is categorized
into adult-type (type 1) and pediatric-type (type 2). The origination of the
histological difference between the two types and how they differ clinically
remain uncertain. We aimed to understand the incidence and clinical
characteristics of the two types of NASH in Korean children, and to investigate
the association between their pathological type and clinical characteristics,
using anthropometric and laboratory data. METHODS: In 38 children with confirmed
NASH, we investigated hepatic pathological findings, and correlating factors
between pathological type and laboratory and anthropometric data (weight
percentile, body mass index (BMI) z-score, and blood pressure percentile). Adult
type NASH was noted in 21 patients and pediatric-type in 17 patients. RESULTS:
Age, sex, BMI, transaminase levels, and insulin resistance were not significantly
different between the two groups. Triglyceride (TG) levels were higher in adult
type NASH (P = 0.033). Hematocrit and albumin levels were lower in adult-type
NASH (P = 0.016 and 0.013, respectively). Hepatic fibrosis was more common in
pediatric-type. The fibrosis scores in patients with adult-type were mostly 0 and
1, whereas the score was 3 in patients with pediatric-type (P = 0.024, 0.004, and
< 0.010, respectively). Anthropometric data, liver function, and insulin
resistance scores did not differ between the two pathological NASH types. TG,
hematocrit, and albumin may be potential factors to predict pathological types.
Fibrosis was observed more frequently in pediatric-type NASH. CONCLUSION:
Monitoring children with pediatric-type NASH for progression to fibrosis or
cirrhosis is recommended.
PMID- 29349945
TI - The Within-Group Discrimination Ability of the Cancer of the Prostate Risk
Assessment Score for Men with Intermediate-Risk Prostate Cancer.
AB - BACKGROUND: Significant clinical heterogeneity within contemporary risk group is
well known, particularly for those with intermediate-risk prostate cancer
(IRPCa). Our study aimed to analyze the ability of the Cancer of the Prostate
Risk Assessment (CAPRA) score to discern between favorable and non-favorable risk
in patients with IRPCa. METHODS: We retrospectively reviewed the data of 203
IRPCa patients who underwent extraperitoneal robot-assisted radical prostatectomy
(RARP) performed by a single surgeon. Pathologic favorable IRPCa was defined as a
Gleason score <= 6 and organ-confined stage at surgical pathology. The CAPRA
score was compared with two established criteria for the within-group
discrimination ability. RESULTS: Overall, 38 patients (18.7% of the IRPCa cohort)
had favorable pathologic features after RARP. The CAPRA score significantly
correlated with established criteria I and II and was inversely associated with
favorable pathology (all P < 0.001). The area under the receiver operating
characteristic curve for the discriminative ability between favorable and non
favorable pathology was 0.679 for the CAPRA score and 0.610 and 0.661 for
established criteria I and II, respectively. During a median 37.8 (interquartile
range, 24.6-60.2) months of follow-up, 66 patients (32.5%) experienced
biochemical recurrence (BCR). Cox regression analysis revealed that the CAPRA
score, as a continuous sum score model or 3-group risk model, was an independent
predictor of BCR after RARP. CONCLUSION: The within-group discrimination ability
of preoperative CAPRA score might help in patient counseling and selecting
optimal treatments for those with IRPCa.
PMID- 29349946
TI - Validation Study of a Korean Version of the Abbreviated University of California,
Los Angeles, PTSD Reaction Index (Abb-UCLA-PTSD RI) for Adolescents.
AB - BACKGROUND: We aimed to verify a Korean version of the Abbreviated University of
California, Los Angeles, Post-Traumatic Stress Disorder Reaction Index (Abb-UCLA
PTSD RI-Korean version) among Korean adolescents to assess post-traumatic stress
in this population. METHODS: We recruited 1,254 adolescents who completed the Abb
UCLA-PTSD RI-Korean version scale, the Child Report of Post-Traumatic Symptoms
(CROPS), the Lifetime Incidence of Traumatic Events (LITE), and the Children's
Depression Inventory (CDI). Test-retest reliability was computed for a randomly
selected 314 participants. Among all the students, 765 were included in the
analysis because 143 students were classified in the normative group (LITE 1) and
622 were in the traumatized group (LITE 4). RESULTS: The internal consistencies
of the nine-item and eight-item versions of the Abb-UCLA PTSD RI-Korean version
were found to be high (Cronbach's alpha = 0.843 and 0.842, respectively). The
criterion-related validity was based on comparison of the Abb-UCLA PTSD RI total
scores between the normative and trauma groups. For the eight-item version, the
normative group (4.6 +/- 4.6) and the traumatized group (8.8 +/- 6.0)
demonstrated better criterion-related validity than those in the nine-item
version (4.5 +/- 4.3 and 8.5 +/- 5.0, respectively). The test-retest reliability
of the eight-item version was better than the nine-item version (r = 0.85 vs.
0.77). A two-factor model with eight items (two items regarding sleep, and the
other six items made up the second factor) showed the best fit. CONCLUSION: Our
results indicate that the eight-item Abb-UCLA PTSD RI-Korean version is a useful
screening tool for post-traumatic stress in Korean adolescents.
PMID- 29349947
TI - Incidence Rate of Atypical Femoral Fracture after Bisphosphonates Treatment in
Korea.
AB - BACKGROUND: Atypical femoral fracture (AFF) has been high-lightened, because it
was associated with the long-term use of bisphosphonate. Comparing western
countries, the incidence rate of AFF was unclear in East Asian patients. Our
purposes were to estimate the incidence rate of radiologically defined AFF in
Korea, and to determine the association between occurrence of AFF and long-term
use of bisphosphonate. METHODS: We conducted a hospital-based, retrospective
cohort study in patients aged >= 45 years, who took bisphosphonate. The
occurrence of AFF was estimated by using incidence rate, and the age-adjusted
incidence rate to U.S. 2010 Census data. The association between occurrence of
AFF and the duration of bisphosphonate use was examined. The cumulative
probability of AFF was plotted per each duration of bisphosphonate use. RESULTS:
Among 10,338 individuals who took bisphosphonate, 13 patients with AFF following
use of bisphosphonate were identified. The incidence rate was 85.9/100,000 person
years (95% confidence interval [CI], 50.2-146.9), and age-adjusted incidence rate
was 72.7/100,000 person-years (95% CI, 29.1-175.8). In Poisson regression
analysis, higher body mass index (BMI) was associated with an increased risk of
AFF (relative risk, 1.2; 95% CI, 1.004-1.359). The cumulative probability of AFF
increased abruptly when the duration of bisphosphonate use was 4 years or more.
CONCLUSION: Among Korean patients, the incidence rate of AFF was on a par with
those of western countries, and this can provide basic information to conduct
further studies by evaluating risk and benefit of continuing bisphosphonate.
PMID- 29349948
TI - Case Report of Kidney Paired Donation (KPD) with Desensitization: the Strategy
and Experience of 3-Way KPD in Samsung Medical Center.
AB - As the need for the organ donation increases, strategies to increase kidney
transplantation (KT) through expanded living donation have become essential.
These include kidney paired donation (KPD) programs and desensitization in
incompatible transplantations. KPD enables kidney transplant candidates with
incompatible living donors to join a registry with other incompatible pairs in
order to find potentially compatible living donor. Positive cross match and ABO
incompatible transplantation has been successfully accomplished in selective
cases with several pre-conditionings. Patients who are both difficult-to-match
due to broad sensitization and hard-to-desensitize because of donor conditions
can often be successfully transplanted through a combination of KPD and
desensitization. According to the existing data, KPD can increase the number of
KTs from living donors with excellent clinical results. This is also a cost
effective treatment as compared with dialysis and desensitization protocols. We
carried out 3-way KPD transplantation with one highly sensitized, positive cross
match pair and with two ABO incompatible pairs. Herein we report our first
successful 3-way KPD transplantation in a single center. To maximize donor
recipient matching and minimize immunologic risk, KPD programs should use proper
algorithms with desensitization to identify optimal donor with simultaneous two-,
three- or more complex multi-way exchanges.
PMID- 29349949
TI - Acute Spinal Subdural Hematoma in a Patient Taking Rivaroxaban.
PMID- 29349950
TI - Issues and Solutions of Healthcare Data De-identification: the Case of South
Korea.
PMID- 29349951
TI - Tissue perfusion rate estimation with compression-based photoacoustic-ultrasound
imaging.
AB - Tissue perfusion is essential for transporting blood oxygen and nutrients.
Measurement of tissue perfusion rate would have a significant impact in clinical
and preclinical arenas. However, there are few techniques to image this important
parameter and they typically require contrast agents. A label-free methodology
based on tissue compression and imaging with a high-frequency photoacoustic
ultrasound system is introduced for estimating and visualizing tissue perfusion
rates. Experiments demonstrate statistically significant differences in depth
resolved perfusion rates in a human subject with various temperature exposure
conditions.
PMID- 29349952
TI - Estimation of cerebral metabolic rate of oxygen consumption using combined
multiwavelength photoacoustic microscopy and Doppler microultrasound.
AB - The metabolic rate of oxygen consumption is an important metric of tissue oxygen
metabolism and is especially critical in the brain, yet few methods are available
for measuring it. We use a custom combined photoacoustic-microultrasound system
and demonstrate cerebral oxygen consumption estimation in vivo. In particular,
the cerebral metabolic rate of oxygen consumption was estimated in a murine model
during variation of inhaled oxygen from hypoxia to hyperoxia. The hypothesis of
brain autoregulation was confirmed with our method even though oxygen saturation
and flow in vessels changed.
PMID- 29349953
TI - [Concept of damage control and the choice of operative methods in the treatment
of pelvic fractures].
PMID- 29349954
TI - [Influence on coagulation function and the therapy effect of damage control
orthopaedics for unstable pelvic fractures and multiple fractures of
extremities].
AB - OBJECTIVE: To retrospectively explore the effects of damage control orthopaedics
concept on coagulation and curative effects in unstable pelvic fractures and
multiple fractures of limbs. METHODS: From March 2014 to December 2015, 40
patients with unstable pelvic fractures and limbs multiple fractures in treatment
group included 22 males and 18 females with an average age of (39.00+/-4.12)
years old were treated with the damage control orthopaedics concept, the ISS
score was (25.36+/-10.81) on average;Other 40 patients with the same trauma in
conventional group included 25 males and 15 females with an average age of
(38.00+/-3.24) years old were treated with conventional method from January 2012
to January 2014 served as control, the average ISS score was 26.56+/-11.44. Matta
criteria and Majeed function standard were used respectively to evaluate the
fracture reduction and therapeutic effects postoperatively. Coagulation function
on the 7th day postoperatively was compared between two groups. RESULTS: All
patients were followed up for 6 to 24 months. According to Matta criteria, the
fracture reduction of the treatment group and the conventional group were (7.38+/
5.09) mm and (10.11+/-6.53) mm, respectively (P<0.05). Majeed functional results
of the treatment group and the conventional group were (86.12+/-6.84) points and
(77.53+/-8.30) points, respectively (P<0.05). On the 7th day after surgery, PT,
APTT, TT of the treatment group were significantly higher than that of the
control group;and Fib of the treatment group was also significantly lower than
that of the conventional group(P<0.05). CONCLUSIONS: The concept of damage
control orthopaedics could effectively improve coagulation function of the
patients with unstable pelvic fractures and limbs multiple fractures, thus are
beneficial to the functional recovery as well as improve the curative effect
postoperatively.
PMID- 29349955
TI - [Clinical application of percutaneous iliosacral screws combined with pubic ramus
screws in Tile B pelvic fracture].
AB - OBJECTIVE: To investigate the application and effect of minimally invasive
percutaneous anterior pelvic pubic ramus screw fixation in Tile B fractures.
METHODS: A retrospective review was conducted on 56 patients with posterior
pelvic ring injury combined with fractures of anterior pubic and ischiadic ramus
treated between May 2010 and August 2015, including 31 males and 25 females with
an average age of 36.8 years old ranging from 35 to 65 years old. Based on the
Tile classification, there were 13 cases of Tile B1 type, 28 cases of Tile B2
type and 15 cases of Tile B3 type. Among them, 26 patients were treated with
sacroiliac screws combined with external fixation (external fixator group) and
the other 30 patients underwent sacroiliac screw fixation combined with anterior
screw fixation (pubic ramus screw group). Postoperative complications,
postoperative ambulation time, fracture healing, blood loss, Majeed pelvic
function score and visual analogue scale(VAS) were compared between two groups.
RESULTS: Fifty-four patients were followed up from 3 to 24 months with a mean of
12 months. There were no significant difference in the peri-operative bleeding
and operation time between two groups(P>0.05). The postoperative activity time
and fracture healing time of pubic ramus screw group were shorter than those of
the external fixator group, the differences were statistically
significant(P<0.05). The Majeed score, VAS score of pubic ramus screw group were
higher than those of the external fixator group, the differences were
statistically significant(P<0.05). The incidence of postoperative complications
of pubic ramus screw was lower than that of the external fixator group, the
difference was statistically significant (P<0.05). CONCLUSIONS: Percutaneous
iliosacral screws fixation combined with the pubic ramus screw is an effective
and safty treatment method to the Tile B pelvic fracture. It has advantages of
early ambulation, relief of the pain and few complications.
PMID- 29349956
TI - [Therapeutic observation of subcutaneous pedicle screw-rod system with modified
placement for Tile B pelvic fractures].
AB - OBJECTIVE: To investigate the feasibility and therapeutic effect of subcutaneous
pedicle screw-rod system with modified placement in treatment of Tile B pelvic
fractures. METHODS: From June 2014 to August 2015, 14 patients with Tile B pelvic
fractures were treated by subcutaneous pedicle screw-rod system with modified
placement in the anterior inferior iliac spine and pubic tubercle. There were 8
males and 6 females, aged from 23 to 65 years with an average of 42 years.
Operative time, intraoperative blood loss, fracture healing and postoperative
complication were observed and clinical effects were evaluated by Matta reduction
standard and Majeed score. RESULTS: All patients were followed up from 8 to 15
months with an average of 10.5 months. Operative time was 25 to 45 min with an
average of 32 min;intraoperative blood loss was 10 to 35 ml with an average of 18
ml. All fractures got primary healing and healed time was 9 to 14 weeks with an
average of 12.5 weeks. No postoperative incision infection, internal fixation
failure and ectopic ossification were found, 4 cases occurred unilateral lateral
femoral cutaneous nerve injury and 1 case occurred unilateral femoral nerve
paralysis, but all restored finally. According to Matta criteria, reduction was
excellent in 7 cases, good in 5 cases, fair in 2 case. According to Majeed score
system, the functional evaluation at last follow-up was excellent in 5 cases,
good in 7 cases, fair in 2 cases with the average score of 81.50+/-8.05.
CONCLUSIONS: Subcutaneous pedicle screw-rod system with modified placement in the
anterior inferior iliac spine and pubic tubercle have advantages of strong
reduction, less trauma and complications, and is a promising surgical method in
the treatment of Tile B pelvic fractures.
PMID- 29349957
TI - [Choices of the internal fixation and approaches on unstable pelvic ring
fractures].
AB - OBJECTIVE: To discuss the suitable surgical approach and the internal fixation of
unstable pelvic pelvic fractures. METHODS: From May 2010 to May 2015, 45 patients
with unstable pelvic fractures were treated with different approaches and
fixations, including 38 males and 7 females with an average age of 45 years
ranging from 21 to 61 years. The course was within 2 weeks. According to Young
Burg classification, 23 patients were lateral compression injuries, 6 patients
were vertical shearing injuries, 16 patients were anterior-posterior compression
injuries. All patients had hip pain and limitation of motion, the X-rays showed
the pelvic ring fracture. RESULTS: All wounds healed well without complications,
45 cases were followed up for a mean period of 13 months (ranged 9 to 21 months).
Patients with hip pain had a good postoperative pain relief. The post-operative X
rays showed the reduction was satisfied and the pelvic ring shaped well.
According to Majeed standards, the final follow-up score was 93.5+/-11.6, 35
cases got excellent results, 8 were good, 2 were fare. CONCLUSIONS: The unstable
pelvic and acetabular fractures are always with compound injury. Beside the
reduction, to decrease the second surgery trauma should take into consideration
as well, the intra-articular reduction and the stability of the pelvic were
especially valued, so combined the different approach with minimal invasive
technique can get good clinical result.
PMID- 29349958
TI - [Biomechanical analysis of the correlation between sacral tilt displacement and
L5S1 disc degeneration].
AB - OBJECTIVE: To biomechanical analysis of the correlation between sacral tilt
displacement and L5-S1 disc degeneration. METHODS: From July 2011 to July 2013,
81 patients with lumbar disc herniation and sacroiliac joint disorder including
45 males and 36 females with an average age of (45.39+/-1.30) years ranging from
18 to 65 years old were selected. The course of the disease ranged from 1 to 144
months with an average of (12.64+/-2.19) months. All patients were taken lumbar
spine lateral X-ray films, the lumbar curvature angle, L4-L5 or L5-S1
intervertebral gap distance between points, and the lumbosacral angle was
measured and correlated analyzed. RESULTS: The lumbar curvature of female
patients with L5S1DH were significantly larger than male patients [(22.18+/-8.62)
degrees vs (16.17+/-4.97) degrees , P<0.05]. Lumbar curvature and lumbosacral
angle showed a positive correlation in LDH (R=0.48, P<0.01,y=7.25+0.38x, P<0.01);
Male patients with L4-5DH were more obvious (R=0.55, P<0.05, y=5.80+0.43x,
P<0.01); Female patients with L5S1DH were particularly evident(R=0.74,
P<0.01,y=0.91x-5.30, P<0.01). The lumbosacral angle and L4-5 intervertebral gap
was a positive correlation in L4-5DH(R=0.27, P<0.05); While L5-S1 intervertebral
gap and lumbosacral angle were not correlated(P>0.05) in L5S1DH. CONCLUSIONS: The
sacral tilt displacement and L5-S1 disc degeneration were closely related to
provide a new understanding philosophy and therapeutic approach for clinical
treatment of intractable lumbar L5S1DH.
PMID- 29349959
TI - [Comparison of the curative effect between over-elbow splint and traditional
small splint fixation in the treatment of comminuted Colles fracture].
AB - OBJECTIVE: To analyze the clinical efficacy of over-elbow small splint fixation
for the treatment of comminuted Colles fractures. METHODS: From October 2013 to
October 2015, 52 patients with comminuted Colles fracture were divided into two
groups (the traditional splint fixation group and the over-elbow small splint
fixation group) according to the treatment strategy. There were 26 patients in
the over-elbow small splint fixation group including 7 males and 19 females with
an average age of (64.615+/-11.475) years old ranging from 38 to 85 years old,
and 26 patients in the traditional splint fixation group including 9 males and 17
females with an average age of (65.269+/-13.162) years old ranging 36 to 91 years
old, respectively. In the over-elbow small splint fixation group, 3 cases were
type A3 fractures, 9 cases were type C1, 7 cases were type C2 and 7 cases were
type C3;in the traditional splint fixation group, 4 cases were type A3, 8 cases
were type C1, 9 cases were type C2 and 5 cases were type C3. After manipulative
reduction, the fractures in traditional splint fixation group were fixed with
traditional small splint, and the fractures in over-elbow small splint fixation
group were added with over-elbow right angle splint for the first three weeks,
then continued fixing like the control group until clinical cicatrization. All
patients in both groups were regularly taken X-ray examination and changed
dressings to obtain the clinical healing. Patients were guided to do functional
exercise after splints were taken off. The therapeutic effects were evaluated
according to modified Green and O'Brein score system after 8 weeks' functional
exercise. RESULTS: All patients got clinical healing without severe complications
in both groups. The shortened length of radius in traditional splint fixation
group was more than that in over-elbow small splint fixation group (5.923+/
1.978) mm VS (2.962+/-1.248) mm(P<0.05). There was no significant difference in
radial incline between two groups. There was a higher wrist score in over-elbow
small splint fixation group compared with traditional splint fixation group
89.615+/-11.482 vs 80.385+/-13.485(P<0.05). CONCLUSIONS: Over-elbow small splint
fixation is better than traditional splint fixation for the treatment of
comminuted Colles fracture because of reliable clinical result and excellent
wrist functional recovery.
PMID- 29349960
TI - [Anterolateral acromial approach for the treatment of proximal humerus in 2-or 3
part fractures-a case-control study].
AB - OBJECTIVE: To explore the clinical curative effect of anterolateral acromial
approach in treating two-and three-part of proximal humeral fractures. METHODS:
Forty-two patients of proximal humeral fractures from January 2010 to June 2014
were analyzed retrospectively, including 23 males and 19 females with a mean age
of 61.5 years old ranging from 40 to 76 years old. Among them, 22 cases were
treated with anterolateral acromial approach and 20 cases were treated with
deltopectoral approach. The operation time, intraoperative blood loss,
postoperative hospitalization days, fracture healing time of two groups were
compared. The shoulder pain after 1 week was assessed by the VAS score. The
postoperative shoulder joint function was evaluated after 3 months and more than
6 months by Constant score. RESULTS: The follow-up time was at final 14 months.
There were significant differences in operation time(P=0.003), intraoperative
blood loss(P=0.001), postoperative hospital day(P=0.013), postoperative shoulder
pain after 1 week(P=0.026), postoperative Constant score after 3 months(P=0.014)
between the anterolateral acromial approach group and the deltopectoral approach
group. There were no significant differences in clinical union time of
bone(P=0.462), postoperative constant score after more than 6 months(P=0.204)
between the anterolateral acromial approach group and the deltopectoral approach
group. There were no breakage of the internal fixation and humeral head
osteonecrosis. CONCLUSIONS: It has some advantages with anterolateral acromial
approach to treat Neer two-and three-part of proximal humeral fractures, such as
short operation time, less intraoperative bleeding, lighter postoperative pain,
quicker recovery of function.
PMID- 29349961
TI - [Total hip arthroplasty for post-traumatic arthritis after internal fixation of
acetabular fracture].
AB - OBJECTIVE: To study the clinical outcome of total hip arthroplasty(THA) for
traumatic arthritis after acetabular fracture. METHODS: From June 2010 to June
2014, 33 hips in 33 patients with traumatic arthritis after acetabular fracture
were retrospective analyzed including 21 males and 12 females with a mean age of
44.6 years old. All the patients received THA with bio-prostheses. Harris score
was used to evaluate the hip function of patients before and after operation, the
X-ray was adopted for radiographic evaluation of the hip prosthesis. RESULTS: All
patients were followed up for 7 to 38 months with an average of 21.6 months. The
Harris score increased from preoperative 53.6+/-2.4 to 94.0+/-3.0 at the final
follow-up, the difference was statistically significant(t=55.37, P<0.05). The X
ray evaluation showed the prosthesis was in good position, no loosening of the
prosthesis, dislocation and periprosthetic osteolysis. CONCLUSIONS: THA is an
effective treatment for the traumatic arthritis after acetabular
fracture;internal fixation of acetabular fractures could not be removed if it
shows difficult but does not affect the prosthesis placement.
PMID- 29349962
TI - [Midterm clinical outcome for ankylosing spondylitis patients with early hip
involved diseases treated with arthroscopic technique].
AB - OBJECTIVE: To study the clinical outcome of manipulation release combined with
arthroscopic debridement and synovia resection under general anesthesia for early
hip involvment in patients with ankylosing spondylitis. METHODS: Manipulation
release combined with arthroscpic debridement and synovium resection were
performed for hip lesion in 22 patients with ankylosing spondylitis from June
2011 to June 2013, incuding 6 males and 16 females with anverage age of 24.7
years ranging from 17 to 23 years. The course of the diseases was from 10 to 41
months(22.1 months on average). After 6 months of conservative treatment, hip
pain and other symptoms were no relief. The preoperative and postoperative follow
up evaluation was performed and compared by the hip movement, VAS pain score,
mHHS score and NAHS score. RESULTS: All the patients were followed up for 26 to
44 months with an average of 30.2 months. The range of motion in active flexion
extension, abduction-adduction, internal-external rotation in 0 degrees flexion
and 90 degrees flexion increased from (78.2+/-10.2) degrees , (36.3+/-6.4)
degrees , (31.1+/-9.2) degrees and (37.3+/-10.5) degrees before operation to
(113.5+/-8.4) degrees , (55.7+/-8.4) degrees , (58.7+/-2.1) degrees and (60.1+/
9.8) degrees after operation, respectively. The VAS scores decreased from 8.5+/
9.4 before operation to 5.5+/-7.1 after operation. The modified Harris and NAHS
scores increased from 60.8+/-6.9 and 56.9+/-6.25 before operation to 88.1+/-10.4
and 84.6+/-5.4 after operation, respectively. CONCLUSIONS: Manipulation release
combined with arthroscopic debridement and synovium resection under general
anesthesia could effectively control the progression of hip lesion in patients
with ankylosing spondylitis restoring the ROM, relieve pain symptoms, delay joint
deformity and ankylosis with less bleeding, faster recovery, and significantly
improve patients' quality of life.
PMID- 29349963
TI - [Research on the stability of teaching robots of rotation-traction manipulation].
AB - OBJECTIVE: To evaluate the stability of teaching robot of rotation-traction
manipulation. METHODS: Operators were required to get the hang of rotation
traction manipulation and had clinical experience for over 5 years. The
examination and data processing of the ten operators in our research were
collected by the teaching robot of rotation-traction manipulation. Traction,
pulling force, maximum force, pulling time, rotational amplitude and pitch range
were recorded and compared for five times(G1, G2, G3, G4 and G5). The
qualification rates were analyzed to evaluate the stability of teaching robot of
rotation-traction manipulation. RESULTS: Nonconforming items were found in G1 and
G2, for instance, pulling force(P=0.074), maximum force(P=0.264) and rotational
amplitude (P=0.531). There was no statistically difference. None nonconforming
item was found in G3, G4 and G5. All data were processed by SPSS and One-way
ANOVA was used to analysis. Pulling force was found statistically different in
G1, compared with G4 and G5(P=0.015, P=0.006). Maximum force was found
statistically different in G1, compared with G4 and G5 (P=0.021, P=0.012). None
differences were found in other comparisons (P>0.05). CONCLUSIONS: The teaching
robot of rotation-traction manipulation used in our research could provide
objective and quantitative indices and was considered to be an effective tool of
assessing the rotation-traction manipulation.
PMID- 29349964
TI - [Biomechanical study of the lateral wall of the femur in the treatment of femoral
intertrochanteric fracture with intramedullary or extramedullary fixation].
AB - OBJECTIVE: To observe the biomechanical effects of the lateral wall of the femur
in treating femoral intertrochanteric fractures with intramedullary or
extramedullary fixation to guide the choice of clinical fixed methods. METHODS:
Twelve adults femur specimens of intertrochanteric fractures were belong to the
type A1 of the AO fracture classification and randomly divided into the lateral
wall complete PFNA group, the lateral wall complete PF-LCP group, the lateral
wall breakage PFNA group, lateral wall breakage PF-LCP group, every group had 3
specimens. The four groups of specimens were subjected to compressive loading
experiment with Universal Material Testing Machine. The maximum loading force was
observed. The distance between fracture ends, the distance of fracture
dislocation and the sliding distance of the fracture fragments along the
intertrochanteric were measured with Calipers. RESULTS: The maximum loading force
of lateral wall complete PFNA group were larger than that of lateral wall
complete PF-LCP group, and the maximum loading force of lateral wall breakage
PFNA group were larger than that of lateral wall breakage PF-LCP group, there
were significant differences (P<0.05). The distance between fracture ends of the
four groups before compression were not significant differences(P>0.05). The
distance between fracture ends, the distance of fracture dislocation and the
sliding distance of the fracture fragments were not significant differences
between lateral wall complete PFNA group and lateral wall complete PF-LCP group
after compression (P>0.05). But the distance between fracture ends, the distance
of fracture dislocation and the sliding distance of the fracture fragments of
lateral wall breakage PFNA group were less than that of lateral wall breakage PF
LCP group(P<0.05). CONCLUSIONS: Intramedullary fixation of intertrochanteric
fractures have stronger loading force. Both intramedullary and extramedullary
fixation of intertrochanteric fractures have strong stability when the lateral
wall of the femur is complete, but intramedullary fixation of intertrochanteric
fractures is stronger stability than extramedullary fixation when the lateral
wall of the femur is broken. So the intramedullary fixation is the first choice
for the treatment of intertrochanteric fracture.
PMID- 29349965
TI - [Clinical characteristics analysis of lumbar disc herniation with symptom
aggravated caused by spinal manipulative therapy].
AB - OBJECTIVE: To discuss the characteristics of lumbar disc herniation (LDH) with
symptom aggravated caused by spinal manipulative therapy (SMT). METHODS: Detailed
clinical profiles of a total number of 10 LDH patients with symptoms aggravated
after SMT were reviewed including 5 males and 5 females with age from 46 to 68
years old, 7 patients of them were more than 50 years old. The clinical data of
10 patients were analyzed involving age, gender, clinical symptoms, signs,
imaging findings, surgical treatment and prognosis. Laminectomy and discectomy
were performed, and follow-up was carried out in all patients. RESULTS: The
duration of symptoms in all the patients before SMT was 4 to 15 years. After the
therapy, an acute exacerbation of back and radicular pain was observed within 24
hours. MRI showed intervertebral disc herniation, 7 patients were observed in L4
L5. The time internal between the exacerbation of presentation and surgery was
23.1 days. No perioperative complications occurred. All the patients were
relieved of radicular pain a few days after surgery. During postoperative follow
up, all patients regained the ability to walk; Eight patients reported a complete
resolution of presentation and the rest two patients were significantly improved.
CONCLUSIONS: SMT should be prohibited in some LDH patients to prevent
neurological damages, in whom there are 5 possible risk factors.
PMID- 29349966
TI - [A medium term therapeutic effects of anatomic locking plate for femoral
intertrochanteric with lateral femoral wall fractures].
AB - OBJECTIVE: To retrospectively study medium term follow-up outcomes of the femoral
intertrochanteric with lateral femoral wall fractures using anatomic locking
plate fixation. METHODS: From June 2010 to January 2013, 18 cases of the unstable
femoral intertrochanteric with lateral femoral wall fractures were treated with
the anatomic locking plate, included 8 males and 10 females with an average age
of 75.5 years ranging from 19 to 83 years old. There were 8 cases of traffic
accident injuries, 6 cases of falls injuries, and 4 cases of falling from high
place. The time from injury to operation was ranged from 1 to 14 days with an
average of 4.5 days. The operation time, intraoperative blood loss and the length
of hospitalization were recorded and analyzed. The fracture union was assessed by
follow-up radiographs and hip functional recovery by PPMS and Harris hip scoring.
RESULTS: All patients were followed up from 36 to 68 months with a mean of(44.8+/
8.8) months. The mean operative time was (61.02+/-38.28) min;the mean blood loss
was (226.00+/-162.52) ml;the mean length of hospitalization was (10.8+/-9.2)
days. During the follow-up period, no infection, deep veintllrombosis, screwed
cut-out and implant failure occurred in all patients. Coxa vara with shortening
deformity was noted in 2 cases. Bone union was found in all the cases. The bone
healing time was ranged from 4 to 10 months with an average of 6.2 months. The
mean PPMS score at the final follow-up was 7.22+/-2.36. The Harris score was
79.46+/-11.02, 5 cases were classified as excellent, 9 as good and 2 as fair.
CONCLUSIONS: Proximal femoral anatomic locking plate can be used in treating
intertrochanteric fractures with compromised lateral wall, which has a satisfied
medium term follow-up outcomes, especially for complex fractures patterns in
which intramedullary nailing may be difficult, and should not emphasis on
premature loading.
PMID- 29349967
TI - [Treatment of children with femoral subtrochanteric fractures by the external
fixation combined with single hip plaster].
AB - OBJECTIVE: To explore curative effects of external fixation combined with single
hip plaster in treating children with femoral subtrochanteric fracture. METHODS:
Form March 2009 to July 2016, 15 children with femoral subtrochanteric fracture
were treated with external fixation combined with single hip plaster, including 9
males and 6 females with a mean age of 8.5 years old ranging from 5 to 14 years
old. According to fracture classification of Seinsheimer, 3 cases were type IIA,
4 cases were type IIB, 3 cases were type IIC, 2 cases were type IIIA, 1 case was
type IIIB, 1 case was type IV, 1 case was type V. Complications and radiographs
were retrospectively reviewed. Postoperative function of hips were evaluated
according to Sanders criteria. RESULTS: All children were followed up from 16 to
48 months with an average of 32 months. No early closure of epiphysis, bone
nonunion and breakage of screw occurred. According to the Sanders score standard
of hip function, the result was excellent in 14 cases, good in 1 case. There were
no hip inversion, limb shortening, excessive growth and other malformations.
CONCLUSIONS: External fixation combined with single hip plaster for the treatment
of children is a safe and effective fixation, which provide a new choice of
femoral subtrochanteric fracture.
PMID- 29349968
TI - [Clinical outcomes of total hip arthroplasty using Wagner SL revision stem in
femoral intertrochanteric fractures for patients with old fracture or painful
arthritis before injury].
AB - OBJECTIVE: To retrospectively study the clinical results of total hip
arthroplasty(THA) using Wagner SL revision stem for patients with femoral
intertrochanteric fracture. METHODS: From 2006 January to 2009 December, 29
consecutive patients with femoral intertrochanteric fractures were performed THA
using Wagner SL revision stem and intertrochanteric reconstruction, including 18
males and 11 females with an average age of 49 years old ranging from 43 to 58.
Among them, 8 cases were oboslete femoral intertrochanteric fractures and 21
cases were the intertrochanteric fractures with painful arthritis before
injuries. After the operation, the follow-up results were evaluated with clinical
and radiographic criteria. The clinical follow-up results were evaluated by
Harris score, limb length discrepancy, ROM of hips and the strength of the hip
abductor. The X-ray imaging follow-up results were evaluated by periprosthetic
osteolysis, prosthesis loosening and radiolucent. RESULTS: All the operations
were successfully completed without serious complications associated with THA.
Twenty-nine cases were followed up for a mean duration of 8.2 years (ranged, 6 to
10). There was no acceptable thigh pain. The first time walk after operation, 8
patients with oboslete intertrochanteric fracture complained the surgical sides
were longer, with the passage of time, the complaint significantly reduced. At 3
months after operation, X-ray films of 21 cases showed intertrochanteric
fractures healed well who had painful arthritis before injuries. An average of 6
months after operation (ranged, 3 to 8), X-ray films of 8 cases of oboslete
intertrochanteric fracture showed that the bone graft and trochanter with obvious
callus connection. There were no obvious prosthesis subsidence on X-ray film at
the final follow-up. The recovery of hip movement range was satisfactory, no hip
abduction strength was weak. More than 6 years after the operation, according to
the Harris scoring evaluation of hip joint, the result was excellent in 18 cases,
good in 9 cases, general in 2 cases. CONCLUSIONS: The clinical results of total
hip arthroplasty using Wagner SL revision stem for patient with femoral
intertrochanteric fracture is a reliable method, intertrochanteric reconstruction
not only makes for prosthesis and joint stability, but also increases bone
reserve.
PMID- 29349969
TI - [Early application of the antibiotic-laden bone cement (ALBC) combined with the
external fixation support in treating the open fractures of lower limbs
complicated with bone defect].
AB - OBJECTIVE: To discuss the curative effect of the early application of the
antibiotic-laden bone cement (ALBC) combined with the external fixation support
in treating the open fractures of lower limbs complicated with bone defect.
METHODS: From December 2013 to January 2015, 36 cases of lower limb open
comminuted fractures complicated with bone defects were treated by the vancomycin
ALBC combined with the external fixation support, including 26 males and 10
females with an average age of 38.0 years old ranging from 19 to 65 years old.
The included cases were all open fractures of lower limbs complicated with bone
defects with different degree of soft tissue injuries. Among them, 25 cases were
tibial fractures, 11 cases were femoral fractures. The radiographs indicated a
presence of bone defects, which ranged from 3.0 to 6.1 cm with an average of 4.0
cm. The Gustilo classification of open fractures:24 cases were type IIIA, 12
cases were typr IIIB. The percentage of wound infection, bone grafting time,
fracture healing time and postoperative joint function of lower limb were
observed. The function of injured limbs was evaluated at 1 month after the
clinical healing of fracture based on Paley evaluation criterion. RESULTS: All
cases were followed up for 3 to 24 months with an average of (6.0+/-3.0) months.
The wound surface was healed well, neither bone infections nor unhealed bone
defects were presented. The reoperation of bone grafting was done at 6 weeks
after the patients received an early treatment with ALBC, some of them were
postponed to 8 weeks till the approximate healing of fractures, the treatment
course lasted for 4 to 8 months with an average of(5.5+/-1.5) months. According
to Paley and other grading evaluations of bone and function, there were 27 cases
as excellent, 5 cases as good, 3 cases as ordinary. CONCLUSIONS: The ALBC
combined with external fixation support was an effective method for early
treatment to treat the traumatic lower limb open fractures complicated with bone
defects. This method was typified with the advantages such as easy operation,
short operation time, overwhelming superiority in controlling infection and
provision of good bone grafting bed, a good bone healing can be realized by the
use of membrane induction technology for bone grafting.
PMID- 29349970
TI - [Total thigh musculocutaneous flap in reconstruction of refractory pressure
ulcers around hips in patients with spinal cord injury].
AB - OBJECTIVE: To discuss the treatment of life-threatening refractory pressure
ulcers around hips in patients with spinal cord injuries(SCI)and evaluate its
clinical outcomes. METHODS: From March 2012 to June 2015, eight paraplegic
patients with life-threatening refractory pressure ulcers around hips were
treated with total thigh musculocutaneous flaps following amputation of proximal
femurs or hips, including 7 males and 1 female with an average age of (52.0+/
2.6) years old ranging from 35 to 68. The coures of disease was from 10 months to
7 years with a mean of(2.9+/-0.2) years. All the 8 patients had compound ulcers
of more than two parts, 7 cases had hip infection on the same side. The area of
superficial wounds ranged from 3.0 cm*3.0 cm to 12.0 cm*15.0 cm. The clinical
effects were evaluated according to infection controlling, wound healing,
improving of nutrition and life quality of patients. RESULTS: All patient were
followed up for 3 months to 2 years with an average of 1.3 years. All flaps
survived, 5 cases obtained wound healing at one-stage, 2 cases had wound
dehiscence and the wounds were closed after a second operation, 1 case had
partial flap necrosis which was healed by dressing change, 1 case had urethral
injury that was repaired in operation. All wounds were cured successfully without
infection and ulcer recurrence during the follow-up period. The nutrition and
quality of life of all cases improved observably after operation. CONCLUSIONS:
The total thigh musculocutaneous flap is effective to reconstruct the refractory
pressure ulcers around hip of patient with SCI. It can rescue life at the cost of
losing one lower limb. It is an operation of last resort for the patients.
PMID- 29349971
TI - [Intraosseous lipoma: retrospective analysis of 19 patients].
AB - OBJECTIVE: To investigate the diagnostic and therapeutic procedures of
intraosseous lipoma. METHODS: From June 1986 to January 2016, 19 patients with
intraosseous lipoma were treated including 12 males and 7 females, aged from 24
to 76 years, a predilection aged was from 40 to 50 years in 13 cases. Symptoms
presented with pain or swelling in 15 patients, the lesions were found
incidentally in 3 patients, another case was bone defect lipoma replacement after
curettage of bone cyst for 4 years. On plain X-ray flims of all bones showed a
well-circumscribed radiolucent area. Diagnosis was established with CT or MRI.
Among them, 16 cases were treated by surgical operation, 3 cases were treated by
concervative treatment. All patients' clinical data, histologic findings and X
ray, CT and MRI were analysed. RESULTS: Total 19 patients were followed up from 9
to 42 months with an average of 15 months. There was no local tumor recurrence in
16 patients after excising the tumors, the remaining 3 patients showed no
enlargement of the lesion. CONCLUSIONS: Surgical intervention is considered as an
unnecessary in the patients diagnosied intraosseous lipoma by MRI or CT. Patients
with symptomatic should adopt surgical treatment with curettage and bone
grafting.
PMID- 29349972
TI - [Current therapy progress on the recurrent patellar dislocation].
AB - Patients who suffer from the recurrent patellar dislocation mainly show the
recurrent dislocation of patellar, giving way, most patients have the history of
trauma or dysplasia of keen joint. Traditional therapies of recurrent patellar
dislocation include medical retinaculum placation, lateral retinaculum release,
tibial tubercle osteotomy, femoral trochleoplasty etc. In recent years, with the
development of anatomical and biomechanical researches on medial patellofemoral
ligament(MPFL), more and more experts focus on the role of MPFL played in
preventing the patellar dislocation. The treatment of recovering and correcting
patellar tracking through MPFL reconstruction has been increasing gradually.
However, till now, there was no therapy which could heal the recurrent patellar
dislocation completely. The specific therapies of recurrent patellar dislocation
are combination therapies, decided according to the anatomical and biomechanical
conditions of patients, for recovering the stability of patients' patellar, the
lower limb alignment and the function of keen-joint.
PMID- 29349973
TI - [Progress on surgical treatment for femoral head-preservering in the precollapse
stage of femoral head necrosis].
AB - Osteonecrosis of the femoral head(ONFH), a refractory disease characterized by
death of the osteocytes and the bone marrow due to inadequate blood supply caused
by various mechanisms, usually leads to the collapse of the femoral head and
malfunction of the hip joint. The crux is to diagnose ONFH early in the
precollapse stage and prevent subsequent progression of collapsing through early
interventions, thus delaying or avoiding the replacement of the hip joint. A
number of joint salvaging operation treatments for early stage ONFH are
available. However, there has been no consensus with regard to the ideal
treatment. The main trend now is to unite core decompression with bone-grafting,
tantalum rod, bone marrow mesenchymal stem cell (BMSC) and other treatments. Also
there are ways of osteotomy altering the angle of the femoral neck to relocate
necrotic tissue from the weight-bearing segment. The implanting of tantalum rod
remains controversial and the advent of bone marrow mesenchymal stem cell (BMSC)
holds huge potential.
PMID- 29349974
TI - [Improvement of arthroscopic thecnique to be helpful for the accurate treatment
of knee joint injury].
PMID- 29349975
TI - [Clinical research on the arthroscopic treatment for recurrent patellar
dislocation by anatomical reconstruction of medial patellarfemoral ligament].
AB - OBJECTIVE: To observe the therapeutic effects of arthroscopic treatment for
recurrent patellar dislocation by anatomical reconstruction of medial
patellarfemoral ligament. METHODS: From June 2009 to December 2014, 25 patients
with recurrent patellar dislocation were treated with anatomical reconstruction
of medial patellarfemoral ligament surgery under arthroscopy. There were 10 males
and 15 females, with an average age of 18.4 years old (ranged, 15 to 25 years old
). There were 15 patients who had a medical history of sports injury, 7 patients
had a chronic impairment history, and the other 3 patients had the symptoms
without obvious predisposing causes. Fourteen patients had injuries on the right
knee and 11 patients had injuries on the left knee. All the patients suffered
from patellar dislocation 3 to 10 times. After operation, the exercise of knee
joint were performed postoperatively. The knee range of motion, Lysholm score,
Kujala score, Insall criteria, Patellar apprehension test and patellar grinding
test were observed to evaluate the clinical effects. RESULTS: All the patients
were followed up, and the duration ranged from 12 to 48 months, with an average
of 24.8 months. After surgery, all the wounds were healed excellent and there
were no complications like surgical incision infection or patellar redislocation.
The ranges of motion was increased from preoperative (105.40+/-5.93) degrees to
postoperative(122.60+/-5.42) degrees . At the latest follow-up, the Lysholm
scores were increased from preoperative 64.12+/-7.49 to postoperative 91.44+/
5.53, the Kujala scores were increased from preoperative 57.88+/-5.10 to
postoperative 92.44+/-2.69. According to the Insall criteria, 19 patients got an
excellent result, 5 good and 1 fair. CONCLUSIONS: It has a satisfactory clinical
therapeutic effect on anatomical reconstruction of medial patellarfemoral
ligament under arthroscopy for the treatment of recurrent patellar dislocation.
It is helpful for the relief of clinical symptoms and improvement of knee joint
function.
PMID- 29349976
TI - [Analysis on the arthroscopy efficacy with different irrigation times for the
treatment of suppurative knee arthritis in elder patients].
AB - OBJECTIVE: To evaluate the curative effect of arthroscopy-assisted irrigation
with different times for the treatment of suppurative knee arthritis in elder
patients. METHODS: From October 2012 to October 2014, 23 old patients with
suppurative knee arthritis were treated with arthroscopic debridement and
continuous irrigation. All the patients were randomly divided into two groups:one
week irrigation group (10 cases) and two-week irrigation group(13 cases). The
ESR, CRP, recovery time of knee skin temperature, joint rang of motion and knee
function were observed to evaluate the therapeutic effects. RESULTS: All the
patients were followed up, and the mean duration was(13.3+/-2.3) months. No
recurrence was observed. The CRP in both groups returned to normal level 2 weeks
after operation. The ESR in two-week irrigation group returned to normal level 2
weeks after operation, while in one-week irrigation group it was still at a high
level, and returned to normal level 3 weeks after operation; there was a
statistical significance between these two groups(P<0.05). The recovery time of
knee skin temperature after operation in two-week irrigation group was (13.4+/
1.2) d on average(ranged, 8 to 17 d), which was less than(15.5+/-1.9) d on
average(ranged, 10 to 20 d) in one-week irrigation group (P<0.05). The knee joint
mobility of all patients 1, 3, 6 months after operation was significantly
improved compared with those before surgery(P<0.05). The knee joint mobility of
patients in two-week irrigation group was better than that in one-week irrigation
group at the first month after operation(P<0.05);but there were no significant
differences between these two groups 3, 6 months after operation. The Lysholm
score of all patients 1, 3, 6 months after operation was significantly improved
compared with those before surgery(P<0.05). The Lysholm score of patients in two
week irrigation group was better than in one-week irrigation group at the first
month after operation(P<0.05);but there were no significant differences between
these two groups 3, 6 months after operation. All the patients had stable knee
functions 3 months after operation. According to the Lysholm scale, 3 patients
got an excellent result, 6 good and 1 poor in one-week irrigation group 6 months
after operation;5 patients got an excellent result, 7 good and 1 poor in two-week
irrigation group;there was no significant differences between these two groups.
CONCLUSIONS: Treatment of suppurative knee arthritis using arthroscopy has such
advantages as minimal invasion and complete debridement, which is helpful to
attenuate inflammation and regain knee function. It is suggested that the
irrigation should be prolonged for two weeks postoperatively.
PMID- 29349977
TI - [Therapeutic effects of internal drainage by expanding arthroscopic gastrocnemius
semimembranosus bursa and cyst wall resection for the treatment of 41 patients
with popliteal cysts].
AB - OBJECTIVE: To investigate the clinical curative effects of internal drainage by
expanding arthroscopic gastrocnemius-semimembranosus bursa(GSB) and cyst wall
resection for the treatment of popliteal cysts. METHODS: A retrospective analysis
of patients from May 2011 to December 2015. Arthroscopic treatment for 41
patients with popliteal fossa cysts, 18 males and 23 females, aged from 34 to 67
years old, averaged 42.6 years old. All the patients had preoperative magnetic
resonance imagings to confirm the diagnosis and identify the valvular
opening(Gastrocnemius-Semimembranosus bursa, GSB), as well as the associated
intra-articular pathology. All the popliteal cysts were unilateral, including 26
cases of right knees and 15 cases of left knees. Five patients had recurrent
popliteal cysts, and all of them underwent initial open Surgery. The duration
from initial surgery to the recurrence ranged from 6 to 17 months(averaged, 11
months). All the patients had underwent arthroscopic treatment of internal
drainage by expanding GSB and cyst wall resection. According to the Rauschning
and Lindgren classification, 5 cases were grade I , 30 cases were grade II and 6
cases were grade III. Preoperative Lysholm score, 83.19+/-6.12 (ranged form 73 to
95). RESULTS: The GSB structure was found in all patients with popliteal cysts
during operation, including cartilage degeneration in 33 cases, medial meniscus
injury in 27 cases, lateral meniscus injury in 7 cases, free body in 8 cases,
pigmented villonodular synovitis in 2 cases, and synovial chondromatosis in 3
cases. There were no complications related to vascular, nerve or surgical
incision. All the patients were followed up, and the duration ranged from 8 to 27
months, with an average of 18 months. No recurrence of cysts was found. According
to the Rauschning and Lindgren classification, there were 9 cases of grade 0, 27
cases of grade I , 4 cases of grade II, 1 case of grade III. Postoperative
Lysholm score:91.32+/-4.26(ranged from 82 to 98). CONCLUSIONS: Arthroscopic
internal drainage by expanding GSB and cyst wall resection surgery in the
treatment of popliteal cysts has the advantages of less trauma, faster recovery
and low relapse rate, which has a good short-term effect.
PMID- 29349978
TI - [Correlation of medial compartmental joint line elevation with femorotibial angle
correction and clinical function after unicompartmental arthroplasty].
AB - OBJECTIVE: To study the correlation of postoperative femorotibial angle with
medial compartmental joint line elevation after unicompartmental
arthroplasty(UKA), as well as the correlation of joint line elevation with the
clinical function by measuring radiological joint line. METHODS: A retrospective
study of 56 patients from July 2012 to August 2015 was performed. The mean body
mass index (BMI) was 23.5 (ranged, 18.3 to 30.1). The standing anteroposterior
radiographs of these patients were assessed both pre-and post-operatively, and
the knee function was evaluated according to HSS grading. The correlation between
postoperative femorotibial angle(FTA) and joint line elevation was analyzed as
well as the correlation between joint line elevation and the clinical function.
RESULTS: The mean medial joint line elevation was (2.2+/-2.0) mm(ranged, -3.3 to
7.0 mm), and the mean FTA correction was (2.3+/-3.0) degrees (ranged, -4.5
degrees to 9.6 degrees ). The mean follow-up period was 12.2 months. There was a
significant correlation between in joint line elevation and FTA
correction(P<0.05), while there was no significant correlation between joint line
elevation and the clinical function(P>0.05). CONCLUSIONS: There was a significant
correlation between medial compartmental joint line elevation and FTA correction
after UKA, and the proximal tibial osteotomy was critical during the procedure.
There was no significant correlation between joint line elevation and the
clinical function, which may be related to the design of UKA prosthesis.
PMID- 29349979
TI - [Capsular-enhanced repair with suture anchors in bipolar hemiarthroplasty for the
treatment of femoral neck fractures in elderly patients].
AB - OBJECTIVE: To evaluate the efficacy of capsular-enhanced repair with suture
anchors in bipolar hemiarthroplasty for the treatment of femoral neck fractures
in elderly patients. METHODS: A retrospective study was designed. From June 2009
to June 2016, 53 senile patients (54 hips)with femoral neck fracture were treated
operatively in Mianyang central hospital (Sichuan, China). There were 21 males
and 32 females, ranging in age from 80 to 97.5 years old (mean, 84.7 years old).
There were 11 hips of Garden type II, 26 hips of Garden type III and 17 hips of
Garden type IV. All the patients underwent bipolar hemiarthroplasty with enhanced
repair of hip capsular. The hip joint was opened by a T shaped incision over
posterior capsule. The posterior hip capsular and short external rotators were
repaired particularly after the bipolar prostheses were implanted. Surgical time,
intra-operative blood loss, mean hospitalization time, deep venous thrombosis,
mortality, hip dislocation, pain, periprosthetic fracture, and other
complications were recorded. The functional outcome was evaluated using the
Harris Hip Score at the last follow-up. RESULTS: The 53 patients (54 hips) were
evaluated during the hospitalization period and a mean follow-up period of 11.5
months(ranged, 3 to 36 months). No dislocation, incision infection and
periprosthetic fracture appeared in this group. The mean surgical time was 65
minutes(ranged, 50 to 95 min). The mean intra-operative blood loss was 213
ml(ranged, 100 to 420 ml) and the mean hospitalization time was 13.3 days(ranged,
5 to 27 days). Two patients with deep vein thrombosis, one patient with pulmonary
embolism and 10 patients with venous plexus thrombosis of calf muscle were
diagnosed postoperatively. The rate of venous thrombosis was 24.53% (13/53). The
patient with pulmonary embolism died 8 days after operation and the other 3
patients died from heart failure 4, 6 and 7 months after operation respectively.
The mortality during first year after hemiarthroplasty was 7.55% (4/53). At the
latest follow-up, 42 patients (43 hips)had no pain, 9 patients had mild pain, and
2 patients had moderate pain. No patients were non-ambulatory. The mean Harris
Hip Score was 91.25+/-8.39, functional outcome was excellent in 44 hips, good in
5, and fair in 5. CONCLUSIONS: The bipolar hemiarthroplasty with capsular
enhanced repair with suture anchors is effective in reducing postoperative
complications of prosthesis dislocation.
PMID- 29349980
TI - [Clinical analysis on arthroscopic debridement for the treatment of early
infection after total knee replacement].
AB - OBJECTIVE: To compare the clinical effects of arthroscopic debridement versus
open debridement on controlling and treatment of infection after total knee
replacement. METHODS: From October 2009 to September 2016 in three hospitals, 11
patients with 11 joints which were infected after total knee replacement were
randomly divided into two groups:5 cases in arthroscopy group and 6 cases in
routine group. Patients in arthroscopy group were treated with arthroscopic
debridement to remove the necrotic tissues, then closed-type irrigation with
sensitive antibiotics by using two sebific ducts were performed continuously for
2 or 3 weeks until the flushing fluid became clear for 3 or 5 days;other 6
patients in routine group were treated with open surgical debridement and the
following procedures in keeping with those in the arthroscopy group. Operation
time, blood loss and incision length were recorded during the operation, and pain
scores were recorded on the 1st, 3rd and 7th day after the operation. The
curative effects were evaluated according to the Hospital for Special Surgery
score system. RESULTS: The local and general symptoms of the 11 patients
disappeared, and the test outcomes of biochemistry, blood and synovial fluid were
normal. All patients were followed up, and the duration ranged from 6 to 18
months. Infection recurrences were observed in 1 case of arthroscopy group and 2
cases of routine group 3 months later after operation, and all these patients who
underwent the second time operation with arthroscopic debridement were cured.
According to the Hospital for Special Surgery score system, 3 cases obtained
excellent result, 2 good, no poor and bad cases in arthroscopy group;3 cases
obtained excellent result, 1 good, 1 poor and 1 bad in routine group.
CONCLUSIONS: If the sensitive antibiotics can be found for the infected joints
without obvious destruction of bone and no prosthesis loosening, it has a better
therapeutic effect by using arthroscopic debridement combined with continuous
drainage and irrigation. The method has a better curative effect with smaller
trauma.
PMID- 29349981
TI - [Clinical results in early and mid term of using the S-ROM femoral stem in
revision].
AB - OBJECTIVE: To investigate and the clinical effect of S-ROM modular stem in femur
reconstruction in hip revision arthroplasty. METHODS: From January 2008 to
January 2016, 21 patients received revision hip arthroplasties using S-ROM stems.
There were 5 males and 16 females with an average of 48.33 years old(range, 29 to
73 years old). There were 13 cases caused by aseptic loosening, 4 cases by
infection, 2 cases by nonunion of sub-tuberosity osteotomy, 1 case for repeated
dislocation, 1 case for traumatic great trochanter fracture. Primary THA
reasons:12 cases for DDH(9 cases for Crowe IV), 5 cases for femoral neck
fracture, 2 cases for necrosis of femoral head, 2 cases for proximal femoral
deformity caused by early infection. The femur bone defects included Paprosky II
in 11 cases, IIIa in 9, and IIIb in 1. Harris hip score , pain score and hip
flexion were recorded before and after operation. The subjective satisfaction was
recorded at the last follow-up. RESULTS: The operation time and blood loss were
189 min(125 to 290 min) and 867 ml (200 to 2 000 ml). At the final followup, the
pain score improved from (17.14+/-9.56) points preoperatively to (41.71+/-2.03)
points (t=11.42, P=0.00). The function score improved from (24.01+/-11.02) points
preoperatively to (49.95+/-5.38) points (t=9.73, P=0.00). Harris hip score
improved from (41.15+/-14.81) points preoperatively to(91.67+/-5.83)
points(t=15.33, P=0.00). The degree of hip flexion increased from (93.10+/-27.27)
points preoperatively to (121.90+/-16.62) points at the last follow-up (t=4.59,
P=0.00). The mean subjective satisfaction was 9.48(10 points system), 14 of which
were completely satisfactory. The last follow-up hip X-ray showed 21 cases of
bone ingrowth, and other femoral stem without loosening or sinking sign
significantly. There were 5 cases with bone anchor syndrome around proximal
femoral cuff. There were 5 cases of proximal femur fracture, 3 cases of lesser
trochanter fracture, 2 cases of greater trochanter fracture intra-operatively.
Due to femoral canal stenosis, there were 4 cases of pre-tied wire at lesser
trochanter to prevent fractures. There was 1 case of traumatic femoral fracture
around stems with a distal oblique fracture, open reduction and locking plate
fixation was performed. Other patients had no nerve stretch injury, dislocation,
infection and lower limb deep vein thrombosis and other complications at the
final follow-up. CONCLUSIONS: S-ROM prosthesis has satisfactory results in hip
revision arthroplasty with Paprosky II and III femoral defects. Especially for
patients with Crowe IV DDH and other proximal femoral deformities, it is possible
to adapt to the medullary cavity morphology. Excellent initial stability, less
complications and long-term biological fixation can be achieved with S-ROM in
femur revision.
PMID- 29349982
TI - [Effects of tranexamic acid combined with temporary drain clamping on
postoperative blood loss in total knee arthroplasty].
AB - OBJECTIVE: To evaluate the efficacy and safety of one dose tranexamic acid
combined with temporary drain lamping in primary unilateral total knee
arthroplasty. METHODS: Total 160 patients undergoing unilateral primary total
knee arthroplasty between January 2012 and December 2013 were randomly divided
into four groups(40 cases in each group):group A (the drain was clamped for 2
hours after the operation and the patients received 20 ml physiological saline),
group B(the drain was clamped for 2 hours after the operation and the patients
received 10 ml tranexamic acid and 10 ml physiological saline), group C (the
drain was clamped for 4 hours after the operation and the patients received 20 ml
physiological saline) and group D(the drain was clamped for 4 hours after the
operation and the patients received 10 ml tranexamic acid and 10 ml physiological
saline). The postoperative hemoglobin level, maximum hemoglobin loss, wound
drainage, blood loss, the volume of blood transfusion, the number of patients
inquiring blood transfusion, venous thrombo embolism rate, and ecchymosis rate
were recorded and compared among the four groups. RESULTS: There was no incision
infection, severe hypoxia, and symptomatic pulmonary embolism in these groups.
There were significant differences in hemoglobin content one day after operation
in each group(F=12.26, P=0.000), in the hemoglobin content 7 days after operation
in each group(F=20.74, P=0.000), in postoperative drainage in each group(F=38.71,
P=0.000);in the amount of invisible red blood cell loss in each group(F=83.41,
P=0.000), and in total red blood cell loss in each group(F=102.68, P=0.000).
Color Doppler ultrasound examination found that the total incidence of VTE was
3%(5/160) and there were no significant differences in each group(P=0.892). There
were no significant differences in postoperative subcutaneous ecchymosis area>1%
incidence(P=0.143). CONCLUSIONS: Topical tranexami acid treatment combined with
temporary clamping of drain for 4 hours could reduce postoperative blood loss,
blood transfusion, and ecchymosis rate without increasing the risk of
thromboembolic event after total knee arthroplasty.
PMID- 29349983
TI - [Treatment of posterior cruciate ligament avulsion fracture with rivet-assisted
hollow nail:a case-control study].
AB - OBJECTIVE: To retrospectively investigate the clinical effect of the rivet
assisted hollow screw in the treatment of posterior cruciate ligament avulsion
fracture. METHODS: Total 49 patients with knee cruciate ligament avulsion
fracture in the ending point of the ligament from January 2010 to December 2014
were divided into the treatment group and the control group. Thirty-one patients
in treatment group were treated with rivet-assisted double cannulate nail,
including 13 males and 18 females, ranging in age from 38 to 51 years old, with a
mean of (40.6+/-5.1) years old; according to Meyers classification, 23 cases of
type 2, 8 cases of type 3; 5 patients were caused by the low energy injury and 26
patients were caused by the high energy injury. Eighteen patients in control
group were treated with double gold hollow screw fixation, including 5 males and
13 females, ranging in age from 36 to 52 years old, with an average age of
(4.16+/-4.7) years old; according to Meyers classification, 14 cases of type 2
and 4 cases of type 3;2 patients were caused by the low energy injury and 16
patients were caused by the high energy injury. The operation time, postoperative
complications, fracture healing time and the last AKS scoring system were
compared between the two groups. RESULTS: All the patients were followed up, and
the duration ranged from 12 to 24 months, with an average of 14.2 months. The
patients in treatment group had no displacement of fracture fragments and
internal fixation failure. The results of AKS score:pain was 48.1+/-1.5, activity
was 21.3+/-2.7, stability was 20.9+/-2.5, walking ability was 47.3+/-1.9, under
the stairs ability was 43.4+/-2.1, the total score was 190.7+/-2.9. There were 2
cases in control group had fracture fragment displacement and 1 patient had nail
withdraw. The results of AKS score:pain was 40.1+/-2.2, activity was 20.1+/-0.2,
stability was 18.1+/-3.2, walking ability was 46.3+/-1.7, under the stairs
ability was 40.2 +/-1.3, the total score was 180.2+/-1.4. Therefore, the
comparison of the above indicators, the results of the treatment group were
better than those of the control group. CONCLUSIONS: Rivet-assisted hollow screw
fixation in the treatment of cruciate ligament avulsion fracture in the ending,
has some advantages such as follows:accurate reduction, less postoperative
complications and better postoperative knee function recovery, therefore it is an
effective way to treat posterior cruciate ligament avulsion fracture.
PMID- 29349984
TI - [Risk factors analysis on wound complications after closed calcaneal frature
operation using lateral extensive L-shaped incision].
AB - OBJECTIVE: To investigate the risk factors of wound complications after closed
calcaneal fracture operation using a lateral extensive L-shaped incision and to
explore the effective interventions to reduce the complications after incision.
METHODS: Retrospective analysis of clinical data of 285 patients(315 calcaneal
fractures) who underwent open reduction and internal fixation by using the
lateral extensive L-shaped incision from January 2011 to January 2015. Eighteen
factors which might cause the complications of calcaneal incision were compared
by univariate analysis, and multiple Logistic regression analysis was performed
for factors with statistically significances. RESULTS: Twenty-nine patients(30
calcaneus) had wound complications among all the 285 patients(315 calcaneus)
after surgery, including 9 patients with incision redness, swelling, oozing or
nonunion;16 patients with skin necrosis or incision rupture, 3 patients with soft
tissue superficial infection, and 2 patients with osteomyelitis. Univariate
analysis showed that fall height(P=0.017), diabetes (P=0.026), smoking(P=0.001),
and operative time(P=0.003) were correlated with incision complications after
surgery. Multivariate analysis showed that diabetes(P=0.029), smoking(P<0.001),
and operative time(P=0.018) were risk factors for incision complications after
operation. CONCLUSIONS: Preoperative smoking cessation, actively control of blood
glucose and shortening the operation time by practicing can effectively reduce
the incision complication after fracture surgery with the lateral extensive L
shaped incision.
PMID- 29349985
TI - [Risk factors analysis for low back pain in patients with multiple sclerosis].
AB - OBJECTIVE: To investigate musculoskeletal disorders and risk factors of low back
pain in multiple sclerosis (MS) patients. METHODS: In this study, patients in our
hospital with confirmed MS with an expanded disabilitystatus scale (EDSS) score
between 4 to 7 were selected. Data of MS history, pain, musculoskeletal
disorders, muscle strength and spasticity in lower limbs were collected. RESULTS:
Among 190 patients, there were 61 males and 129 females, with an average age
of(54.9+/-9.2) years old. The mean disease duration was(19.3+/-9.9) years, and
the median EDSS score was 6. Forty-two patients were relapsing-remitting type, 45
patients were primary progressive type, and 93 patients were secondary
progressive type. The most common musculoskeletal disorders were described as
follows:knee osteoarthritis (15 cases), claw toe (13 cases) and genu recurvatum
(12 cases). Seventy-nine patients with prevalence low back pain was higher than
in patients with a progressive type(secondary: OR=2.958, P=0.007 9,
primary(OR=2.629, P=0.039 8) and in patients who had a visual dysfunction at EDSS
score(OR=1.411, P=0.012 4). The prevalence was reduced in male patients(OR=0.306,
P=0.001 4). CONCLUSIONS: The progressive type of MS and visual dysfunction
increased the risk of low back pain in these patients.
PMID- 29349986
TI - [Observation of curative effects of musculoskeletal ultrasound-guided needle
knife on the degenerative meniscus disease].
AB - OBJECTIVE: To observe the curative effect of musculoskeletal ultrasound-guided
needle-knife on the degenerative meniscus disease, and to provide a new method in
the treatment of degenerative meniscus disease. METHODS: Seventy-seven patients
with degenerative meniscus disease treated in the Third Affiliated Hospital of
Beijing University of Chinese Medicine from January 2015 to September 2015 were
selected, including 30 males and 47 females, aged from 44 to 66 years old, with
an average of 57.5 years old. VAS scores, Lysholm scores and distance of meniscal
protrusion were analyzed and compared before treatment, 2 weeks and 1 month after
treatment. The curative effect was summarized at last. RESULTS: The mean Lysholm
scores were 51.63+/-15.26(before treatment), 77.13+/-11.82(2 weeks after
treatment) and 87.56+/-8.65(1 month after treatment). The mean VAS scores were
7.080+/-1.574 (before treatment), 2.630+/-0.310(2 weeks after treatment) and
0.850+/-0.177(1 month after treatment). The mean of the distance of meniscal
protrusion scores were 0.400+/-0.156 (before treatment), 0.298+/-0.140 (2 weeks
after treatment) and 0.240+/-0.110 (1 month after treatment). VAS scores and
Lysholm scores were improved significantly compared with preoperative results.
The distance of meniscal protrusion showed an obvious improvement after
treatment. CONCLUSIONS: The treatment of musculoskeletal ultrasound-guided needle
knife has advantages of high accuracy position and excellent effectiveness for
degenerative meniscus disease. The treatment provides safety operation and
significantly improves quality of life in patients without any complications.
PMID- 29349987
TI - [CT measurement and clinical application of double-row suture anchor
reconstruction for the treatment of Tossy type III acromioclavicular joint
dislocation].
AB - OBJECTIVE: To study feasibility and reliability of reconstruction of the
acromioclavicular ligament with double-row suture anchor for the treatment of
acromioclavicular joint dislocation through coracoid coronal CT measurement, and
to provide a new operation method for treating acromioclavicular joint
dislocation. METHODS: Total 60 healthy people received CT examination of shoulder
joint, including 30 males and 30 females, ranging in age from 18 to 50 years old.
The coronal width, thickness and 20 degree camber angle in the medial part of the
toot of coronal were measured using CT scan. The results were applied to clinical
treatment for 12 patients with acromioclavicular joint dislocation of Tossy III
type. RESULTS: The width in the medial part of the root of the coracoid
was(17.65+/-1.82) mm(left side) and (17.67+/-1.80) mm(right side) in males;
(16.55+/-1.78) mm(left side) and (16.52+/-1.74) mm (right side) in females. The
vertical thickness of the roots of the coracoid: (13.11+/-2.11) mm(left side) and
(13.16+/-2.09) mm(right side) in males;(12.79+/-2.21) mm(left side) and (12.76+/
2.19) mm (right side) in females. The thickness of 20 degrees camber angle of the
coracoid roots: (16.32+/-1.74) mm (left side) and (16.30+/-1.69) mm(right side)
in males; (15.68+/-1.44) mm(left side) and (15.67+/-1.43) mm(right side) in
females. Total 12 patients were treated with anchor nail with extraversion 20
degrees. The postoperative X-ray films showed bone anchors were located in the
coracoid process, no bone splitting. CONCLUSIONS: Double-row suture anchor of 5
mm diameter nails can be placed into coracoid with extraversion 20 degrees, which
is safety.
PMID- 29349988
TI - [Comparison of analgesic effects between multimodal and patient-controlled
intravenous analgesia in patients with rheumatoid arthritis in the perioperative
period of total knee arthroplasty].
AB - OBJECTIVE: To compare the analgesic effect between multimodal and patient
controlled intravenous analgesia(PCIA) in patients with rheumatoid arthritis(RA)
in the perioperative period of knee joint replacement. METHODS: From June 2015 to
June 2016, 40 RA patients undergoing total knee arthroplasty were randomly
divided into two groups. There were 20 patients in PCIA group, including 3 males
and 17 females, with an average age of(59.6+/-2.3) years old, who received
controlled instillation of sufentanil analgesia controlled by an intravenous
analgesia pump. There were 20 patients in multiple model analgesia group,
including 2 males and 18 females, with an average age of(56.3+/-1.3) years old,
who were treated with continuous femoral nerve block, local injection of knee
joint and combined buprenorphine patches. The VAS score and the incidence of
adverse reactions and HSS score were compared between the two groups after
operation. The advantages and disadvantages of the two modes of analgesia were
evaluated. RESULTS: On the 6 th and 24 th hours after surgery, the VAS scores of
the multimodal analgesia group were significantly lower than those of the PCIA
group(P<0.01). On the 48 th hour after surgery, the VAS scores was significantly
lower in the multimodal analgesia group than those in PCIA group(P<0.000 1), both
in the state of motion and at rest. On the 1 st week after surgery, the HSS score
of the multimodal analgesia group was significantly higher than that in the PCIA
group(P<0.000 1). The pain score and the degree of activity in HSS score of the
multimodal analgesia group were better than those in PCIA group (P<0.05). The
functional score of multimodal analgesia group was significantly better than that
of PCIA group(P<0.01). But there was no significant difference in muscle strength
scores between two groups. CONCLUSIONS: Multimodal analgesia is an ideal
analgesic plan for total knee arthroplasty TKA patients with RA in perioperative
period, which has good effects and little adverse reaction.
PMID- 29349989
TI - [Artificial radial head replacement for the treatment of comminuted fractures of
the radial head].
AB - OBJECTIVE: To assess the clinical effects of artificial radial head prosthesis
replacement for the treatment of comminuted fracture of the radial head. METHODS:
From June 2011 to June 2015, 25 patients with radial head comminuted fracture
were treated with artificial radial head replacement, including 10 males and 15
females, ranging in age form 24 to 61 years old(mean, 40 years old). The
functional recovery of the patients suffering from limb and elbow in different
periods, the activity degree of the elbow joint and the function of the elbow in
the latest follow-up were compared. RESULTS: All the patients were followed up,
and the duration ranged from 12 to 48 months, averaged 26 months. There were no
complications such as infection, elbow instability, subluxation of the distal
radioulnar joint, and myositis ossificans. The VAS, Broberg and Morrey elbow
function score were improved 6, 9 months after operation compared with that 3
months after operation(P<0.05). There were significant differences in elbow
flexion and extension, rotation activity between injured side and healthy side 3,
6, 9 months after operation(P<0.01), but no significant differences between
injured side and healthy side at the latest follow-up(P>0.05). At the latest
follow-up, according to Broberg and Morrey elbow function evaluation criteria, 16
cases got an excellent result, 7 good and 2 poor. CONCLUSIONS: It can maximize
the recovery of elbow joint stability and quicken early functional exercise,
prevent and reduce the occurrence of complications by using the artificial radial
head replacement therapy to repair comminuted fracture of the radial head. The
short-term curative effect is satisfactory, but the long-term effect needs
further observation.
PMID- 29349990
TI - [Experimentation of the relationship between medial or lateral patellar
stabilizer and patellofemoral stabilization].
AB - OBJECTIVE: To study the contribution of medial or lateral stabilizer to the
stability of the patella, to explore the function and effect of releasing the LPR
clinically and to provide a biomechanical basis for the clinical treatment of
patellar instability(PI). METHODS: The quadriceps femoris of 6 fresh human
cadaver knees were loaded to simulate a normal condition of muscle strength.
First the loading force was measured and recorded, which subluxated the patella
with the different degrees of knee flexion. Intervention 1:released the medial
patellar retinaculum(MPR) to simulate pathologic conditions, then repeated the
above manipulates and recorded the loading force. Intervention 2:released the LPR
furthermore to simulate clinical surgical treatment, then repeated the above
manipulates and recorded the loading force. RESULTS: After releasing the MPR, the
loading force which subluxated the patella were decreased obviously, and there
were significant differences between the two groups(P<0.05). The above loading
force was further decreased after the further release of LPR, but the difference
was not significant(P>0.05). CONCLUSIONS: MPR plays an important role in
maintaining the stability of the patella and in the normal trajectory of the
patellofemoral joint. The attention should be paid to the repair or
reconstruction of the MPR in the treatment for patella recurrent lateral
dislocation subluxation. Releasing the LPR is not a best choice.
PMID- 29349991
TI - [Effects of creating a tunnel through intercondylar fossa under arthroscopy for
the treatment of complex tears at the medial meniscus posterior horn].
AB - OBJECTIVE: To discuss the advantages of the arthroscopic treatment for complex
tears of the medial meniscus posterior horn by creating a tunnel passageway
through the intercondylar fossa. METHODS: All 127 patients including 24 males and
103 females with complex tears at the medial meniscus posterior horn were
reviewed. The age of all patients ranged from 45 to 78 years old, with an average
of 67 years old. All 127 patients were treated with partial meniscectomy, in
which 112 patients were treated with partial meniscectomy smoothly with three
incisions (anterior medial incision, anterior lateral incision, high anterior
lateral incision), and 15 patients were treated with four incisions (anterior
medial incision, anterior lateral incision, high anterior lateral incision,
posterior medial incision). Four aspects were estimated:whether the meniscus
posterior horns could be observed totally and conveniently, whether tools could
be pushed to target area conveniently, the damage of adjacent cartilages,
operation time(the operation time of partial meniscectomy). RESULTS: Posterior
horns of all patients were totally and conveniently observed, tools were
conveniently pushed to the target area in all cases, and all the cases had no
iatrogenic injuries at adjacent cartilages. The operation time of partial
meniscectomy at posterior horns with three incisions ranged from 5 to 10 minutes,
and it ranged from 10 to 30 minutes with four incisions. CONCLUSIONS: It is very
convenient and fast of the arthroscopy to treat complex tears of the medial
meniscus posterior horn by creating a tunnel through the intercondylor fossa.
Iatrogenic injuries of the adjacent cartilages were prevented to the greatest
extent.
PMID- 29349992
TI - [Excision of necrotic and infected tissues combined with induced membrane and
external fixator technique for the treatment of chronic osteomyelitis in tibia
after fracture operation].
AB - OBJECTIVE: To investigate the clinical efficacy of excision of necrotic and
infected tissues combined with induced membrane and external fixator technique to
treat chronic osteomyelitis in tibia after fracture operation. METHODS: From June
2011 to June 2014, a total of 13 patients with tibia osteomyelitis were treated
with excision of necrotic and infected tissues and external fixator technique in
the first stage. There were 8 males and 5 females, ranging in age from 16 to 67
years old with an average of (37.3+/-14.3) years old. Within 6 to 8 weeks the
induced membrane was formed and the induced membrane technique was applied to
promote new bone forming in the second stage. RESULTS: Thirteen patients had no
reinfection and achieved complete bone healing after 24 to 52 months follow-up.
All the patients had satisfactory function. CONCLUSIONS: Excision of necrotic and
infected tissues combined with induced membrane and external fixator technique to
treat chronic osteomyelitis in tibia after fracture operation can provide
satisfactory results.
PMID- 29349993
TI - [Accurate osteotomy assisted by individualized navigation templates for the
treatment of children cubitus varus].
AB - OBJECTIVE: To investigate the feasibility and accuracy of a new navigation
template for osteotomy in cubitus varus based on computer assistant design and 3D
printing technology. METHODS: The preoperative CT images of 15 children with
cubitus varus from June 2015 to June 2016 were collected. According to the above
data, the individual osteotomy navigate template match the distal humerus was
designed by the software and printed by the 3D printer. Accurate osteotomy was
performed with the assistant of the navigate template in the operation. Internal
fixation of the osteotomy site was performed with 2 Kirschner wires. After
surgery, a long arm plaster was applied with 20 degrees of elbow flexion. All
the patients underwent radiographic and clinical evaluations before surgery and
at the follow-up examination. RESULTS: During the operation, the navigate
template with the individual design of 3D printing technology matched the bony
markers of distal humerus. Accurate and simple osteotomy were performed along the
resected surface of the navigation template. None of the cases required any kinds
of revision surgery or had any complaint of cosmetic appearance. Average union
time was 6.7 weeks(ranged, 6 to 8 weeks). Twelve patients got an excellent result
and 2 got a good result according to the criteria described by Bellemore. There
were no cases with complications of infection or ulnar nerve palsy or joint
stiffness. CONCLUSIONS: With the help of 3D printing technology, the accurate
osteotomy in cubitus varus assisted by individualized navigate template can be
realized. This technology can restore normal anatomical structure of the elbow
joint to the greatest extent. It is worthy of popularization and application.
PMID- 29349994
TI - [Double hip and knee joint replacement for the treatment of rheumatoid arthritis
with severe osteoporosis:a case report].
PMID- 29349995
TI - [Progress on graft and fixation options of arthroscopic anterior cruciate
ligament reconstruction].
AB - Anterior cruciate ligament injury is one of the most common injuries of knee
joint. Arthroscopic reconstruction of anterior cruciate ligament is the most
commonly performed procedure. A variety type of fixation techniques are being
used nowadays, such as interference screw, cortical suspension fixation and
transfix, all of which can achieve good effect, with both advantages and
disadvantages. However, the healing of reconstructed grafts is a complicated and
long-term process, which can be affected by many factors. The mechanical
properties of the grafts are also changed greatly in all stages of healing
process, adding variables for the post-operative rehabilitation.
PMID- 29349996
TI - [To implement minimally invasive endoscopic spinal surgery proactively and safely
by mastering multiple techniques].
PMID- 29349997
TI - [Surgical outcome of percutaneous endoscopic technique for highly migrated disc
herniation via three different approaches].
AB - OBJECTIVE: To analyze the clinical effects of percutaneous endoscopic technique
via three different approaches for highly migrated lumbar disc herniation.
METHODS: The clinical data of 68 patients underwent percutaneous endoscopic
technique from June 2011 to June 2014 were retrospectively analyzed. There were
43 males and 25 females, aged from 11 to 77 years old with an average of (42.29+/
15.92) years. The patients were divided into three groups according to different
operative approaches, of them, 45 cases were by transforaminal approach (group
A), 15 cases by translaminar approach (group B), and 8 cases by transpedicular
approach (group C). There was 1 case in level L2,3, 12 cases in L3,4, 36 cases in
L4,5, 19 cases in L5S1. The herniated disc was migrated superiorly in 23
patients, inferiorly in 45 patients. MRI were available to confirm migrated disc
pre-and post-operatively. Operation time, loss blood volume, intraoperative and
postoperative complications, time of back to work (postoperative recovery time)
were recorded. Preoperative and postoperative VAS were used to evaluate low back
pain and sciatica and JOA and MacNab criteria were used to evaluate functional
recovery. RESULTS: All the operations were successful and all the patients were
followed up from 12 to 40 months with an average of (18.0+/-15.9) months. Seven
patients(3 cases in group A, 3 cases in group B, 1 case in group C) complicated
with transient paraesthesia (hyperalgesia or hypesthesia), and the symptoms
relieved after symptomatic treatment with neurotrophic medicine, at final follow
up, no symptoms were left. One case in group B complicated with dura mater
tearing during operation and it was untreated, there was no resulted
complications such as headache and sinus tract of skin. In group A, B, C, the
mean VAS score of sciatica improved from preoperative 6.93+/-1.34, 6.33+/-1.23,
6.13+/-1.73 to 0.80+/-0.87, 0.73+/-0.70, 0.38+/-0.52 at final follow-up; and JOA
score improved from preoperative 9.09+/-2.62, 9.80+/-2.31, 10.50+/-2.93 to
26.82+/-1.53, 25.93+/-1.58, 26.50+/-1.51 at final follow-up,
respectively(P<0.05). There was no significant difference among three
groups(P>0.05). There was no significant difference in loss blood volume,
postoperative recovery time among three groups. But operation time of group B was
shorter than other two groups. According to MacNab criterion to assess the
clinical effects, 42 cases got excellent results, 21 good, 5 fair. CONCLUSIONS:
Percutaneous endoscopic technique is a safe and effective method for surgical
treatment of highly migrated herniation. The decision of operative approach
should be made by characters of anatomy. By tanspedicular approach the lesion
could be found directly. However, it depends on good skill and equipment.
PMID- 29349998
TI - [Comparative study of minimally invasive percutaneous pedicle screw fixation and
open surgery in the treatment of thoracolumbar fractures].
AB - OBJECTIVE: To compare the clinical outcomes of minimally invasive percutaneous
pedicle screw fixation and open surgery in the treatment of thoracolumbar
fracture. METHODS: A retrospective study of patients who had undergone surgery
for thoracolumbar fracture from June 2014 to December 2014 was performed. Sixty
one cases were included and 29 cases were treated by minimally invasive
percutaneous pedicle screw fixation (minimally invasive group) and 32 cases were
treated by the traditional open pedicle screw fixation(open group). The
differences in the total length of the incision, intraoperative fluoroscopy
times, operative time, blood loss, the preoperative and postoperative visual
analogue scale(VAS), postoperative bedridden time and hospital stay were
compared. And the preoperative and postoperative anterior vertebral body height
and Cobb angle of the kyphosis were also compared. RESULTS: Compared with the
open group, the total length of incision was smaller and intraoperative blood
loss was less, bedridden time and hospital stay were shorter, and pain of the
wound was less in the minimally invasive group. Postoperatively, the anterior
vertebral body height was retorted and the Cobb angle of the kyphosis was
corrected obviously in both groups. But no significant difference in the imaging
results was found between two groups(P>0.05). CONCLUSIONS: Minimally invasive
percutaneous pedicle screw fixation has the similar fixation efficacy with open
surgery in treating thoracolumbar fracture. However, it can avoid extensive
muscle stripping, and obviously reduce the surgical incision, operative time,
postoperative pain, bedridden time and hospital stay. According to the clinical
efficacy, it is worthy of clinical application.
PMID- 29349999
TI - [Percutaneous endoscopic lumbar discectomy combined with epidural injection for
prolapsed lumbar disc herniation].
AB - OBJECTIVE: To assess the effect of percutaneous endoscopic lumbar discectomy
(PELD) combined with epidural injection for prolapsed lumbar disc
herniation(PLDH). METHODS: In this prospective randomized controlled study, the
clinical data of 126 patients who had undergone a PELD because of a single-level
PLDH from March 2014 to June 2015 were analyzed. There were 67 males and 59
females, ranging in age from 17 to 75 years old with an average of(41.0+/-13.5)
years old, 9 cases were L3,4, 76 cases were L4,5 and 41 cases were L5S1.
According to the random number table, the patients were randomized into two
groups, with 63 patients in each group. Patients in group 1 were injected normal
saline after PLED, patients in group 2 were subjected to an epidural injection of
Diprospan, Lidocaine and Mecobalamine after PLED. All the patients were followed
up from 6 to 20 months with the mean of 12.4 months. Complications, the
postoperative hospital stay, the period of return to work, visual analogue scale
(VAS) and Japanese Orthopedic Association (JOA) score were compared between two
groups, and clinical outcomes were evaluated according to modified MacNab
criteria. RESULTS: All the operations were successful, and no complications were
found. The mean postoperative hospital stay and the period of return to work in
group 1 were (4.61+/-1.25) days and (4.31+/-0.47) weeks, respectively, and in
group 2 were (2.53+/-0.69) days and (3.14+/-0.52) weeks, there was significant
differences between two groups(P=0.000). Postoperative VAS and JOA scores in two
groups were obviously improved (P=0.000). At 1 day, 1 week, 1 month after
operation, VAS, JOA scores in group 2 were better than that of group 1(P=0.000),
and after 6 months, there was no significant difference between two
groups(P>0.05). According to the modified MacNab criteria, 39 cases got excellent
results, 21 good, 3 fair in group 1, and which in group 2 were 41, 20, 2,
respectively, there was no significant difference between two groups(P=0.087).
CONCLUSIONS: PELD is an mini-invasive technique for PLDH, it can fleetly reduce
pain and improve function. And combination with epidural injection has the
advantages of pain releasing and function improving in the short-term
postoperative period, and it can decrease postoperative hospital stay and time of
returning to work, and it is a safe and effective method.
PMID- 29350000
TI - [Percutaneous vertebroplasty and open vertebroplasty for metastatic spinal
tumor].
AB - OBJECTIVE: To explore the clinical application and therapeutic effect of
percutaneous vertebroplasty(PVP) and open vertebroplasty for metastatic spinal
tumor. METHODS: The clinical data of 126 patients with metastatic spinal tumor
underwent surgery and obtained follow-up from January 2012 to March 2016 were
retrospectively analyzed. These 126 cases were divided into two groups according
to different operative methods. The metastatic tumor of 43 cases encroached
vertebral canal oppressing spinal cord and nerve root, they were treated with
open operation(open vertebroplasty group);and other 83 cases without obviously
spinal cord or nerve root compression, or unfit for open operation, were treated
with PVP (percutaneous vertebroplasty group) . VAS score, ECOG and Frankel grade
were used to evaluate the pain and neurofunction in two groups.All out-hospital
patients were followed up every 3 months for 1 time. X-ray, CT, MRI were examined
in follow-up. RESULTS: A total of 112 vertebrae underwent PVP with the median
surgical time of 50 min;VAS scores decreased significantly at 2 days after
operation, which maintained till 1 month later; ECOG grade at 1 month decreased
significantly;44 of 112 vertebrae suffered from asymptomatic bone cement leakage,
no complications such as nerve injury or pulmonary embolism was found; the median
survival time was 16 months. While for open vertebroplasty group, the median
surgical time was 160 min and blood loss was 1 000 ml; postoperative VAS scores
and ECOG grade at 1 month decreased significantly. Postoperative Frankel grade of
36 patients got improvement in 41 patients with spinal cord functional
disturbance(87.8%); and 29 of 40 patients with incompleteness out of motor
function were full recovery(76.3%); 12 cases (27.9%) occurred complications and
the median survival time was 11 months. CONCLUSIONS: The different vertebroplasty
treatments can be selected for patients with metastatic spinal tumor, which can
relieve the pain, improve the nerve function, reconstruct the spinal
stabilization, maintain the local control and raise the life quality.
PMID- 29350001
TI - [Analysis of complications of percutaneous endoscopic lumbar discectomy].
AB - OBJECTIVE: To analyze the complications of lumbar intervertebral disc herniation
treated with percutaneous endoscopic lumbar discectomy(PELD), and discuss how to
avoid these complications. METHODS: The data of 132 patients with lumbar
intervertebral disc herniation underwent PELD from October 2013 and June 2015
were retrospectively analyzed, including 85 males and 47 females with an average
age of 42.9 years old. There were 6 cases of L3,4, 68 of L4,5 and 58 of L5S1. The
incidences of intraoperative and postoperative complications were analyzed.
RESULTS: There was spinal dura mater injury in 1 patient, but no cerebrospinal
fluid leakage and nerve function deficit was found, the muscle strength did not
decrease postoperatively and the incision healed well. Two patients converted to
open surgery ultimately because of stenosis of the intervertebral foramen and
adhesion between nucleus pulposus and spinal dura mater; two patients complicated
with early recurrence(in 3 months);nucleus pulposus residue developed in 3
patients; all of them were treated by open surgery and got satisfactory results.
One patient with heart disease history complicated with supraventricular
tachycardia after surgery and 2 patients with the increased cerebrospinal fluid
pressure during surgery. CONCLUSIONS: PELD have a steep learning curve, and the
technology is a safe and effective method in treating lumbar disc herniation, but
the beginners must have enough open surgery experience, and to grasp indications
strictly.
PMID- 29350002
TI - [Progress on laminoplasty in spinal canal disease].
AB - Surgery is the preferred method for the treatment of spinal canal disease,
surgical method involves laminectomy and laminoplasty. The ideal spinal surgery
not only should fully expose the spinal canal, completely resect the occupied
position and remove the spinal cord compression, but also should maintain the
stability of spinal biomechanics. Because of the different realization of
clinician to safeguard and rebuild the spinal stabilization during opertion of
spinal canal disease, and choice of surgical method and how to maintain the
stability of spine biomechanics has become a hot of research in this field. Many
scholars have studied it in order to reduce the influence of laminectomy on the
spinal stability. Laminoplasty can directly relieve the nerve roots compression
caused by increasing or reconstruction of vertebral canal volume, and allow the
migration of spinal cord to dorsum and depart from disc and vertebral body.
Laminoplasty not only can fully expose and decompress during operative, but also
may prevent the postoperative spinal instability. In addition to these condition
of extensive disease, severe bone destruction or combined with osteoporosis, the
laminoplasty is the most ideal method for single spinal canal disease in
theoretically.
PMID- 29350003
TI - [Anatomical feature of lumbar and S1 pedicle in patients with thoracolumbar
kyphosis secondary to ankylosing spondylitis].
AB - OBJECTIVE: To measure the correlative parameters of vertebral pedicles from L1 to
S1 by CT scan in the patients with thoracolumbar kyphosis secondary to ankylosing
spondylitis(AS) and disc degenerative disease(DDD), and analyze their anatomical
difference in order to provide the selection and placement of pedicle screw
during operation. METHODS: The clinical data of 30 male AS patients (AS group)
with the mean age of(35.7+/-9.5) years (ranged, 23 to 51) and 30 male DDD
patients (DDD group) with the mean age of(52.4+/-8.9) years(ranged, 39 to 64)
underwent surgery in our institution from March 2012 to November 2014 were
analyzed. The CT scans of lumbar and sacrum were performed before surgery. The
parameters of vertebral pedicle from L1 to S1 were measured and compared,
including pedicle width (PW), pedicle screw path length (PL), pedicle height
(PH), pedicle transverse angle (EA), and pedicle inclined angle (FA). Paired
sample t-test was used to detect the divergence in the above-mentioned data
between left and right sides. In addition, results between two groups were
compared using independent sample t-test. RESULTS: The study showed that a
gradual increase in the average pedicle width both AS group and DDD group from L1
to S1. The average PW of AS group was bigger than DDD group in L5 and S1(P<0.05),
it was(16.47+/-2.66) mm and (21.76+/-2.97)mm vs. (14.51+/-2.11)mm and (18.87+/
2.14) mm respectively;the average PL of DDD group was smaller than AS group from
L1 to S1(P<0.05); the both maximum of PL were in L3 segment; the average EA of AS
group was smaller than DDD group from L1 to S1; the average FA of AS group was
significantly smaller than DDD group from L3 to S1, (P<0.05), was(-2.88+/-10.24)
degrees , (-7.88+/-10.22) degrees , (-7.70+/-10.40) degrees , (-5.15+/-10.25)
degrees vs. (4.05+/-2.21) degrees , (7.79+/-4.38) degrees , (7.07+/-3.21)
degrees , (12.62+/-3.21) degrees , respectively. CONCLUSIONS: Increasing the
strength of internal fixation is feasible to insert the larger and bigger pedicle
screws in low lumbar and S1 among AS patients, while the EA should be decreased
properly and the direction on the sagittal plane should be adjusted.
PMID- 29350004
TI - [Posterior debridement and bone grafting via intervertebral space combined with
internal fixation for the treatment of lumbosacral tuberculosis].
AB - OBJECTIVE: To explore the clinical effects of posterior debridement, bone
grafting via intervertebral space combined with internal fixation for the
treatment of lumbosacral tuberculosis. METHODS: The clinical data of 32 patients
with lumbosacral tuberculosis underwent the procedure of one-stage posterior
intervertebral debridement, bone grafting and internal fixation from January 2007
to July 2013 were retrospectively analyzed. There were 17 males and 15 females,
aged from 27 to 63 years with an average of (49.8+/-9.2) years. The course of
disease was from 5 to 18 months with the mean of (10.7+/-3.2) months. There was
involved the vertebral body of L5 in 1 case, the intervertebral space of L5S1 in
8 cases, and the vertebral body of L5 or S1 combined with intervertebral space of
L5S1 in 23 cases. VAS, ESR, CRP, the lumbosacral angle, the height of
intervertebral space of L5S1, and ASIA grade were used to evaluate clinical
effects. RESULTS: All the patients were followed up from 18 to 39 months with an
average of 21.6 months. Operative time was 120 to 260 min with the mean of 175
min, and intraoperative bleeding was 700 to 1 450 ml with the mean of 1 050 ml.
VAS before operation was 8.4+/-1.6, then descended to 3.5+/-0.8(P<0.05) on the
3rd month after operation and redescended to the level of 1.7+/-0.6(P<0.05) at
the final follow-up. The ESR and CRP before operation were (48.8+/-10.2) mm and
(58.6+/-5.6) mg/L, respectively, then decreased to (35.6+/-6.9) mm and (22.5+/
4.3) mg/L (P<0.05) at the 3rd month after operation and returned to the normal
level at the final follow-up. The height of intervertebral space of L5S1 and
lumbosacral angle before operation were (7.7+/-0.4) mm and (19.3+/-1.2) degrees ,
respectively, then improved to (10.3+/-0.3) mm and (22.4+/-1.5) degrees on the
3rd month after operation(P<0.05), and maintained such level, no obvious lost at
later. According to ASIA grade, 8 cases were grade C, 19 were grade D, 5 were
grade E before operation, and at final follow-up, 1 case still was grade D,
others were grade E. CONCLUSIONS: The procedure of posterior debridement, bone
grafting via intervertebral space combined with internal fixation is an effective
and safe method in treating lumbosacral tuberculosis, it can effectively debride
tuberculose focus, maintain the spinal stability, and improve the dysfunction
with less complication.
PMID- 29350005
TI - [Relationship between the prediction of the opening angle and the increased value
of cross-sectional area in single open-door laminoplasty].
AB - OBJECTIVE: To evolve the formula of relationship between opening angle of
laminoplasty and the increased value of cross-sectional area, and to predict the
opening angle according to the opening size of lanminoplasty. METHODS: From
January 2013 to December 2015, 26 patients underwent single open-door
laminoplasty in C3-C7. Among them, 10 patients with ossification of posterior
longitudinal ligament, there were 6 males and 4 females, aged from 39 to 58 years
old with an average of 49.2 years; and 16 patients with cervical spondylotic
myelopathy, there were 10 males and 6 females, aged from 40 to 58 years old with
an average of 50.2 years. Through the changes of spinal canal shape between
preoperation and postoperation to set up the regular geometric model, and to
deduce the formula of the relationship between the opening angle of laminoplasty
and the increased value of cross-sectional area, and predict the formula of
opening angle. According to the preoperative and postoperative CT scan, the
needed parameters were measured, and were substituted in the above formula to get
the change of cross-sectional area before and after operation, predicting the
opening angle of laminoplasty. The differences between the change of cross
sectional area before and after operation, predictive the opening angle of
laminoplasty and practical measured data were analyzed by statistical methods,
thus to verify the feasibility of formula in practical application. RESULTS: All
imaging data of 26 patients were obtained. There were significant differences in
changes of cross-sectional areas in every patients (laminoplasty in C3 to C7)
before and after operation in the same segment(P<0.01). The increasing extent in
cross-sectional areas was gradually diminished following the opening angle
increasing. There was no significant difference between the opening angle
attained by formula and the data measured by software in the same
segment(P>0.05). CONCLUSIONS: Increment of cross-sectional areas following C3-C7
laminoplasty can be accurately attained and the opening angle can also be
predicted by a certain formula, which can help surgeons to attain the accurate
opening angle and reduce the postoperative complications.
PMID- 29350006
TI - [The shor-term clinical outcomes and safety of extreme lateral interbody fusion
combined with percutaneous pedicle screw fixation for the treatment of
degenerative lumbar disease].
AB - OBJECTIVE: To evaluate the early efficacy and safety of extreme lateral interbody
fusion (XLIF) combined with percutaneous pedicle screw fixation for lumbar
degenerative disease. METHODS: From January 2013 to June 2014, 13 patients with
degenerative lumbar disease were treated with XLIF combined with percutaneous
pedicle screw fixation, including 8 cases of lumbar instability, 5 cases of mild
to moderate lumbar spondylolisthesis;there were 5 males and 8 females, aged from
56 to 73 years with an average of 62.1 years. All patients were single segment
fusion. Operation time, perioperative bleeding and perioperative complications
were recorded. Visual analogue scale (VAS) and Oswestry Disability Index (ODI)
were used to evaluate the clinical efficacy. Interbody fusion rate was observed
and the intervertebral foramen area changes were compared preoperation and
postoperation by X-rays and CT scanning. RESULTS: The mean operation time and
perioperative bleeding in the patients respectively was(62.8+/-5.2) min
and(82.5+/-22.6) ml. One case occurred in the numbness of femoribus internus and
1 case occurred in the muscle weakness of hip flexion after operation, both of
them recovered within 2 weeks. All the patients were followed up from 12 to 19
months with an average of 15.6 months. VAS was decreased from preoperative 7.31+/
0.75 to 2.31+/-0.75 at final follow-up(P<0.05); ODI was decreased from
preoperative (42.58+/-1.55)% to (12.55+/-0.84)% at final follow-up(P<0.05). At
final follow-up, CT scanning confirmed 8 cases completely fused and 5 cases
partly fused;the intervertebral foramen area was increased from preoperative
(94.86+/-2.44)mm2 to (150.70+/-7.02)mm2(P<0.05). CONCLUSIONS: Extreme lateral
interbody fusion combined with percutaneous pedicle screw fixation is an ideal
method and can obtain early good clinical effects in treating lumbar degenerative
disease.
PMID- 29350007
TI - [The metabolic profilings study of serum and spinal cord from acute spinal cord
injury rats 1H NMR spectroscopy].
AB - OBJECTIVE: To establish the rat model of acute spinal cord injury, followed by
aprimary study on this model with 1H NMR based on metabonomics and to explore the
metabonomics and biomarkers of spinal cord injury rat. METHODS: Twenty eight-week
old adult male SD rats of clean grade, with body weight of (200+/-10) g, were
divided into sham operation group and model group in accordance with the law of
random numbers, and every group had 10 rats. The rats of sham operation group
were operated without damaging the spinal cord, and rats of model group were made
an animal model of spinal cord incomplete injury according to the modified
Allen's method. According to BBB score to observate the motor function of rats on
the 1th, 5th, and 7th days after surgery. Postoperative spinal cord tissue was
collected in order to pathologic observation at the 7th day, and the metabolic
profilings of serum and spinal cord from spinal cord injury rats were studied by
1H NMR spectroscopy. RESULTS: The hindlimb motion of rats did not obviously
change in sham operation group, there was no significant difference at each time
point;and rats of model group occurred flaccid paralysis of both lower
extremities, there was a significant difference at each time; there was
significant differences between two groups at each time. Pathological results
showed the spinal cord structure was normal with uniform innervation in shame
group, while in model group, the spinal cord structure was mussy, and the neurons
were decreased, with inflammatory cells and necrotic tissue. Analysis of
metabonomics showed that concentration of very low density fat protein (VLDL),
low density fat protein (LDL), glutamine, citric acid, dimethylglycine (DMG) in
the serum and glutathione, 3-OH-butyrate, N-Acetyl-L-aspartic acid (NAA),
glycerophosphocholine (GPC), glutamic acid, and ascorbate in spinal cord had
significant changes(P<0.05). CONCLUSIONS: There are significant differences in
metabolic profile from serum and spinal cord sample between model group and sham
operation group, it conduces to explain the changes of small molecular substances
in serum and spinal cord tissue after spinal cord injury, this provides the
research basis for targeted research on the role of metabolic markers in patients
with acute spinal cord injury.
PMID- 29350008
TI - [Surgical treatment for open tarsometatarsal joint injury].
AB - OBJECTIVE: To discuss the surgical method and clinical efficacy for open
tarsometatarsal joint injuries. METHODS: From March 2011 to January 2015, 21
patients with open tarsometatarsal joint injuries were treated with stage-surgery
method, including 14 males and 7 females with an average age of 45.6 years old
ranging from 20 to 75 years. Injury site occurred in the left foot of 13 cases
and right foot of 8 cases. Traffic injury was in 5 cases, crush injury in 6
cases, heavy crushing was in 10 cases. According to Myerson to classify for
tarsometatarsal joint injury, 5 cases were type B2, 9 cases were type C1, and 7
cases were type C2. And according to Gustilo to typing for soft tissue injury, 5
cases were type IIB, 10 cases were type IIIA, 6 cases were type IIIB. Fracture
healingand complications were observed after operation and clinical effects were
evaluated according to the midfoot score of AOFAS. RESULTS: All the patients were
followed up from 11 to 40 months with an average of 16.2 months. The fracture
healing time was from 10 to 16 weeks with an average of 12.3 weeks. No
complications such as deep infection, nonunion and osteomyelitis were found.
Midfoot score of AOFAS at last follow-up was 83.0+/-14.9, 9 cases got excellent
results, 8 good, 2 fair, 2 poor. Two patients complicated with severe traumatic
arthritis once again underwent tarsometatarsal arthrodesis. CONCLUSIONS: For the
treatment of open tarsometatarsal joint injury, reasonable debridement,
comprehensive assessment for the soft tissue injury, correctly grasp the surgical
indications and time of internal fixation, can reduce the incidence of deep
infection and osteomyelitis.
PMID- 29350009
TI - [Etiological analysis, preventional and therapeutical strategies for the
unsatisfied cervical posterior decompression surgery].
AB - OBJECTIVE: To discuss the causes of unsatisfied cervical posterior decompression
surgery and describe the overhauling strategies and precaution. METHODS: The
clinical data of 14 patients required revision surgery were retrospectively
analyzed, and these patients with unsatisfied effects were due to cervical
posterior decompression surgery from January 2012 to December 2014. Overhauling
reasons were analyzed and then different revision procedures were performed. The
functions of cervical cord and ambulation were evaluated respectively by modified
Japanese Orthopedic Association(mJOA) score and Nurick grade according to the
course order:preoperative for the first time, pre-revision and at final follow
up. Improvement rate of nerves function were calculated before and after
operation for the first time, before and after revision. Above data were
statistically analyzed by SPSS16.0 software. RESULTS: Reoperation reasons
including 2 patients with the insufficiency width of laminectomy, 2 patients with
the inadequate length of decompression, 2 patients with nerve root and spinal
cord compression caused by fractured collapse, 4 patients with closed the door of
vertebral lamina, 1 patient with less open-door angle, 2 patiens with
ossification of posterior longitudinal ligament (1 case complicated with close
the door), 2 patients with cervical spine kyphotic deformity aggravating (1 case
complicated with close the door), 1 patient with nerve root canal stenosis caused
by uncovertebral joint hyperplasia. Preoperative for the first time, pre-revision
and at final follow-up, mJOA scores were 11.89+/-1.67, 13.11+/-1.09, 15.61+/
0.59, and Nurick grades were 4.21+/-0.58, 3.57+/-0.51, 1.71+/-0.47, respectively.
There was significant difference between final follow-up and preoperative for the
first time, pre-revision(P<0.05). Improvement rate of nerve function was (22.33+/
9.49)% with bad before and after operation for the first time, and (64.60+/
9.88)% with good before and after revision, with statistical
significance(P<0.05). CONCLUSIONS: Individualized revision surgery based on
different causes for unsatisfied cervical posterior decompression can improve the
function of spinal cord. Preoperative carefully analyzing the etiological
factors, thoroughly decompression can reduce the revision rate.
PMID- 29350010
TI - [A comparative study of outcome between single cage and double cages interbody
fusion combined with pedicle screw fixation in treatment of isthmic
spondylolisthesis].
AB - OBJECTIVE: To compare the clinical effects of isthmic spondylolisthesis by a
single cage or double cages interbody fusion combined with pedicle screw
fixation. METHODS: The clinical data of 172 patients with isthmic
spondylolisthesis underwent surgery from March 2000 to August 2008 were
retrospectively analyzed. All cases underwent posterior pedicle screw fixation
and interbody fusion, 89 cases with single cage fusion and 83 cases with double
cages fusion. In single cage group, there were 56 males and 33 females, aged from
18 to 63 years old with an average of(41.60+/-8.20) years;25 cases were in L4
segment and 64 cases were in L5;according to the Meyerding standard, 32 cases
were I degree, 46 cases were II degree and 11 cases were III degree. In double
cage group, there were 49 males and 34 females, aged from 20 to 65 years old with
an average of(43.30+/-6.39) years;21 cases were in L4 and 62 cases were in
L5;according to the Meyerding standard, 25 cases were I degrees, 45 cases were II
degree, and 13 cases were III degree. The operative time, intraoperative blood
loss, postoperative drainage volum, bone fusion rate, intervertebral space height
and the improvement of clinical symptoms were compared between two groups.
RESULTS: All the operations were successful and all patients were followed up for
18 to 83 months with an average of 4 years and 3 months. The operative time,
intraoperative blood loss, postoperative drainage volume in single cage group
were less than of double cage group(P<0.05). Two weeks after operation, the
intervertebral space height was significantly increased in two groups(P<0.05),
and there was no significant difference at the last follow-up between two groups.
At 16 months after operation, all bone grafts of patients got bony fusion by X
rays. At the last follow-up, there were no statistically significant difference
in JOA, ODI and VAS score between two groups, no pedicle screw loosening and
breaking were found. CONCLUSIONS: Single cage interbody fusion combined with
pedicle screw fixation is as effective as with double cages interbody fusion in
treatment of isthmic spondylolisthesis, it has the advantages of short operative
time and less blood loss.
PMID- 29350011
TI - [Treatment of ossification of ligamentum flavum complicated with lumbar spinal
stenosis].
AB - OBJECTIVE: To investigate the imaging characteristic and operation outcome of
ossification of ligamentum flavum with lumbar spinal stenosis. METHODS: January
2013 to January 2016, 9 patients with ossification of ligamentum flavum with
lumbar spinal stenosis were treated, included 5 males and 4 females, aged from 51
to 63 years old with an average of 57 years old. All patients complained
intermittent claudication and radiating pain at lower limb. The pathologic change
regions examined by CT or MRI were as follows:2 cases in L4,5 and L5S1, 5 in L,,
and 2 in L5S1. Four patients underwent simple laminectomy and 5 patients
underwent laminectomy and discectomy, interbody fusion and internal fixation with
pedicle screw. Clinical effects were evaluated according to JOA score, which
items included subjective symptom, daily activity limitation, clinical sign and
bladder function. RESULTS: No complications such as infection or nerve injury
were found after operation. The follow-up period was from 12 to 60 months with an
average of 24 months. The low back pain and radiating pain at lower limb improved
significantly and walking distance approached normal at final follow-up;and JOA
scores improved obviously. CONCLUSIONS: Ossification of ligamentum flavum has the
special characteristic on CT scan, which decide the selection of operation
method. The operative aim is effectively spinal decompression and rebuilding
lower lumbar stability by minimally invasive surgery.
PMID- 29350012
TI - [Application of debridement and bone autografting combined with proximal femoral
anatomical plates for benign tumor in proximal femur].
AB - OBJECTIVE: To explore the clinical effects of debridement and bone autografting
combined with proximal femoral anatomical plate in treating benign tumor in
proximal femur. METHODS: From January 2010 to October 2014, 30 patients with
benign tumor in proximal femur were treated with debridement, autogenic ilium,
autogenic ilium and allogeneic bone implant, and anatomic plate fixation. Among
them, there were 13 males and 17 females aged from 12 to 68 years old with an
average of 42 years old. The courses ranged from 1 month to 2 years with an
average of 9 months. MSTS scoring were observed and compared before and after
operation, and also applied to evaluate lower-extremity function. X-ray was
examined to evaluate healing of focus. Postoperative complications were observed.
RESULTS: All patients were followed up from 12 to 48 months with an average of 29
months. MSTS score at the final following-up (27.06+/-2.59) was higher than
preoperative (16.44+/-1.35), and there was significant difference(P<0.05). X-ray
at the final following-up showed bone graft fusion, pathological fracture were
recover consciously, internal fixation was well, no loosening, deformation and
displacement occurred. One case occurred incision fat liquefaction and 1 patient
with giant cell tumor of bone relapsed at 13 months after operation. CONCLUSIONS:
Debridement and bone autografting combined with proximal femoral anatomical plate
is an effective method in treating benign tumor in proximal femur. It could
control tumor, relieve pain, promote function and prevent occurrence of
pathologic fractures.
PMID- 29350013
TI - [Closed reduction and percutaneous double K-wires internal fixation for the
treatment of multisegmental fracture of humeral shaft].
AB - OBJECTIVE: To observe the clinical effects of closed reduction and percutaneous
double K-wires internal fixation in treating multisegmental fracture of humeral
shaft. METHODS: From January 2009 to April 2015, 27 patients with multisegmental
fracture of humeral shaft were treated with closed reduction and percutaneous
double K-wires internal fixation, including 10 males and 17 females, ranging in
age from 26 to 81 years with an average of 52 years;the disease course ranged
from 2 hours to 6 days with an average of 1.5 days. Operative time,
intraoperative blood loss, hospital stay, fracture healed time, complications
were observed and recovery of shoulder joint function was evaluated by Constant
Murley shoulder score. RESULTS: All the patients were followed up from 12 to 24
weeks with an average of 16 weeks. Operative time was 20 to 40 min with an
average of 28 min; intraoperative blood loss was 5 to 25 ml with an average of 10
ml;hospital stay was 3 to 5 days with an average of 3.5 days. All fractures got
bone healing and healed time was 12 to 22 weeks with average of 14 weeks.
Postoperatively 1 case complicated with wire tail bulging and local irritation
symptoms, and the symptoms disappeared when the wire was removed out after the
fracture healing; 1 case complicated with local infection after wire tail
disengaging, and recovered through anti-septic treatment. According to the
Constant-Murley standard of shoulder joint function, 10 cases got excellent
results, 15 good, 2 fair, with scores of 89.1+/-2.7. CONCLUSIONS: Closed
reduction and percutaneous double K-wires fixation for the treatment of
multisegmental fractures of humeral shaft have advantages of simpler
manipulating, less bleeding, less invasive, less complications, and shoulder and
elbow joint can obtain good recovery. But closed reduction and percutaneous
double K-wires internal fixation cannot be effective against rotation and provide
axial stability, the immoblization with a sling or other auxiliary methods should
be applied.
PMID- 29350014
TI - [A case report of hysterical paralysis during kyphoplasty in a patient with
compression fracture of lumbar vertebra].
PMID- 29350015
TI - [Application of finite element method in spinal biomechanics].
AB - The finite element model is one of the most important methods in study of modern
spinal biomechanics, according to the needs to simulate the various states of the
spine, calculate the stress force and strain distribution of the different groups
in the state, and explore its principle of mechanics, mechanism of injury, and
treatment effectiveness. In addition, in the study of the pathological state of
the spine, the finite element is mainly used in the understanding the mechanism
of lesion location, evaluating the effects of different therapeutic tool,
assisting and completing the selection and improvement of therapeutic tool, in
order to provide a theoretical basis for the rehabilitation of spinal lesions.
Finite element method can be more provide the service for the patients suffering
from spinal correction, operation and individual implant design. Among the design
and performance evaluation of the implant need to pay attention to the individual
difference and perfect the evaluation system. At present, how to establish a
model which is more close to the real situation has been the focus and difficulty
of the study of human body's finite element.Although finite element method can
better simulate complex working condition, it is necessary to improve the
authenticity of the model and the sharing of the group by using many kinds of
methods, such as image science, statistics, kinematics and so on.
PMID- 29350016
TI - Biomarkers of treatment efficacy in patients with chronic spontaneous urticaria.
AB - Summary: Background. Currently there are no biomarkers useful to predict the
future evolution and the therapeutic response in patients with chronic
spontaneous urticaria (CSU). Objective. To review the available information on
biomarkers that might be applied for the follow up of the response to guideline
recommended therapies for CSU. Methods. A review of the medical literature on CSU
potential clinical and laboratory biomarkers in PubMed and MEDLINE including the
terms urticaria, chronic urticaria, chronic idiopathic urticaria, chronic
spontaneous urticaria, antihistamines (AHs), omalizumab (OMA), cyclosporine
(CyA), and treatment. Results. Clinical manifestations that were associated to
poor responses to AHs were atopy, asthma, rhinitis / rhinosinusitis, thyroid
disease, hypertension, higher disease activity and duration. Laboratory markers
of AH resistance that have been reported include Complement C5a fraction,
Autologous Serum Skin Test (ASST), Basophil Activation Test (BAT), D-dimer and
LCN2 adipokine. Basophil Histamine Release Assay (BHRA), ASST, and basophil
CD203c-upregulating activity in the serum correlated with favorable response to
OMA, whereas disease duration and severity, BAT, BHRA, and D-dimer levels were
associated with better responses to CyA. Conclusion. Some promising biomarkers
useful for patient management in CSU, have been identified in the literature.
There is, however, an urgent need of new, easy-to-perform markers that can be
made widely available for the optimal care of patients suffering CSU.
PMID- 29350017
TI - Skin prick test analysis reveals cross-sensitization to tomato profilin and grass
pollen in nasobronchialallergic patients with history of tomato food allergy.
AB - Summary: The association between grass pollen sensitization and food allergy to
tomato is of great interest. We report here, the first such study in Indian
population. We investigated 246 allergic rhinitis / asthma patients by diagnostic
case history and skin prick test (SPT); grass pollen mix, tomato extract and
purified tomato profilin were used for SPT. Tomato profilin was purified by
affinity chromatography, and analyzed by HPLC (95% purity) and SDS-PAGE (14 kDa).
We observed that 38% of the patients had sensitization to both grass pollen and
tomato fruit, of which 92% were sensitized to tomato profilin. Among patients
with a history of food allergy to tomato fruit, the association was more
pronounced (66%). Tomato profilin appears to be an important cross-sensitizing
panallergen in respiratory allergic patients in the Indian subcontinent.
PMID- 29350018
TI - Allergy and high trait anxiety are related to increases in heart rate
variability: results of naturalistic long-term design study.
AB - Summary: A number of studies report heart rate variability (HRV) changes in
allergic as well as high trait anxious people, and associations between allergic
inflammation and trait anxiety. This study investigated HRV of 20 low anxious
allergic, 19 healthy high trait anxious and 18 healthy low anxious, in
naturalistic setting. On arranged research days, subjects performed measurements
using portable ECG device and subjective self-assessment of perceived stress.
Five repeated measurements data from each subject have shown increases in overall
HRV, as well as HRV on respiratory frequencies in both allergy and high trait
anxiety. Subject's sex was an important factor, because HRV increases in allergy
were only apparent in women. Data from self-assessment show no differences in
experienced stress attributable to allergy, only to trait anxiety.
PMID- 29350019
TI - Cypress pollen allergy is responsible for two distinct phenotypes of allergic
rhinitis different from other pollinosis.
AB - Summary: Different phenotypes of allergic rhinitis have been identified based on
the seasonality of the allergen involved. Within pollinosis, importance has to be
paid to the responsible pollen species. Guidelines for clinical management are
mostly based on studies performed in patients with grass pollen allergy. Only few
data is available on tree pollen allergy and more specifically on cypress pollen
allergy. We focused on the clinical and biological features of cypress pollen
allergy to determine whether it is associated with a specific phenotype of
allergic rhinitis or not. Our results suggest that cypress pollen can be
responsible for two distinct phenotypes of rhinitis, both different from other
pollinosis. In the most common phenotype, cypress pollen was not responsible for
bronchial hyperresponsiveness or systemic inflammation. Close attention has to be
paid to the allergen involved in allergic rhinitis. Different phenotypes leading
to different pharmacological strategies may apply.
PMID- 29350020
TI - Cutaneous drug reactions to antiepileptic drugs and relation with HLA alleles in
the Turkish population.
AB - Summary: Background and objective. Many studies have shown associations between
HLAB*15:02, HLA-A*31:01 and carbamazepine (CBZ)-induced delayed cutaneous
hypersensitivity reactions. The aim of this study is to evaluate a possible
association between delayed cutaneous reactions to antiepileptic drugs (AEDs) and
certain HLA-A and HLA-B alleles in the Turkish population. Methods. The study
consisted of 3 groups: Group I (reactive group) included the patients who had
documented delayed cutaneous reactions to any antiepileptic drug. Group II (non
reactive group) included the patients who have been on antiepileptic treatment at
least for three months without any adverse reactions. Group III consisted of
healthy subjects. The HLA-A and B alleles were analyzed in all groups. Results.
Forty patients (29 female) had experienced different hypersensitivity reactions
due to AEDs: maculopapular exanthema (26 patients), Stevens-Johnson syndrome (6
patients), drug rash with eosinophilia and systemic symptoms (7 patients), toxic
epidermal necrolysis (1 patient). Lamotrigine (11) and CBZ (10) were the most
common culprit drugs involved in the reactions. The HLA-B*15:02 was not present
in any of the study groups. However, HLA-B*35:02 was found in 4 patients from the
reactive group, while it was not observed in non-reactive patients and was
detected in only one healthy subject (p = 0.021). Conclusion. Although our
preliminary results did not indicate a strong allele association with AED
hypersensitivity, HLA-B*35:02 appears to be a candidate allele for MPE / DRESS /
DIHSS induced by AED's in Turkish population. Further studies with a larger
sample size may result in more comprehensive data about the genetic tendency for
AED hypersensitivity in the Turkish population.
PMID- 29350021
TI - Bodybuilding protein supplements and cow's milk allergy in adult.
AB - Summary: We report a case of a previously healthy 24-year-old man with a 3-month
history of gastrointestinal symptoms during exercise and also few minutes after
the ingestion of cow's milk (CM) without exercise. He reported the ingestion of a
blend of hydrolyzed whey and casein proteins for bodybuilding for the last 2
years. The in vivo tests showed positivity to CM, alpha-lactalbumin, beta
lactoglobulin and casein extracts, and also to the protein supplement. The serum
specific IgE was positive for CM, beta-lactoglobulin and alpha-lactalbumin. The
in vivo and in vitro tests results suggested an IgE-mediated CMA. Adult-onset CMA
has been rarely reported, and to our knowledge this is the first case possibly
related to bodybuilding supplements. The authors theorize that the presentation
of large amounts of proteins in the gastrointestinal tract may favor
sensitization.
PMID- 29350022
TI - An unusual case of positive sIgE to Galactose-alpha-1,3-galactose from South
Italy.
AB - Summary: We report the case of a 38-year-old man who was bitten several times
during his life by a tick. He didn't report any previous history of anaphylaxis
after the ingestion of red meat. The serum specific IgE showed positivity to
alpha-Gal. The proximity of the bits didn't increase the titer of IgE antibodies
to alpha-gal. We could hypothesize that the frequency of the exposure to the tick
Corresponding author bites and the amount of tick bites during his lifetime
induced a sort of tolerance in this patient.
PMID- 29350023
TI - Erratum to: Plasma betaine concentrations correlate with plasma cortisol but not
with C-reactive protein in an elderly population
PMID- 29350025
TI - Synthesis, Spectroscopy, and Morphology of Tetrastilbenoidmethanes.
PMID- 29350024
TI - Accurate Quantification of Radiosulfur in Chemically Complex Atmospheric Samples.
AB - An ultralow-level liquid scintillation counting (LSC) technique has been used in
measuring radiosulfur (cosmogenic 35S) in natural samples. The ideal half-life of
35S (~87 days) renders it a new way to examine various biogeochemical problems. A
major limitation of the technique is that complex chemical compositions in
atmospheric samples may lead to color quenching of LSC cocktails, a serious
problem prolonging the pretreatment time (>1 week) and hampering the accurate
determination of 35S. For application of the technique where many of the most
important atmospheric chemical processes are examined, significant interferences
arise and accurate analysis in small samples is not possible. In this study, we
optimized the LSC method to minimize/eliminate color quenching in high
sensitivity 35S measurements. The analytical performance of this new method was
evaluated using control laboratory experiments and natural aerosol samples.
Results show that the new method offers comparable accuracy as the traditional
method for normal environmental samples [bias: <+/-0.03 disintegrations per
minute (DPM)] and significantly shortens the pretreatment time to less than 3
days. For samples that were heavily contaminated by color-quenching agents, the
accuracy of this new method is notably higher than that of the traditional method
(maximum bias: -0.3 vs -1.5 DPM). With the growing use of radiosulfur in the
field of Earth and planetary sciences, the accurate determination of 35S would
provide a reliable field-based constraint for modeling 35S production in the
atmosphere and allow a wide range of atmospheric, hydrological, and
biogeochemical applications.
PMID- 29350026
TI - Steric and Acidity Control in Hydrogen Bonding and Proton Transfer to trans
W(N2)2(dppe)2.
AB - The interaction of trans-W(N2)2(dppe)2 (1; dppe = 1,2
bis(diphenylphosphino)ethane) with relatively weak acids (p-nitrophenol,
fluorinated alcohols, CF3COOH) was studied by means of variable temperature IR
and NMR spectroscopy and complemented by DFT/B3PW91-D3 calculations. The results
show, for the first time, the formation of a hydrogen bond to the coordinated
dinitrogen, W-N=N...H-O, that is preferred over H-bonding to the metal atom,
W...H-O, despite the higher proton affinity of the latter. Protonation of the
core metal-the undesirable side step in the conversion of N2 to NH3-can be
avoided by using weaker and, more importantly, bulkier acids.
PMID- 29350027
TI - Evaluation of Drug Exposure and Metabolism in Locust and Zebrafish Brains Using
Mass Spectrometry Imaging.
AB - Studying how and where drugs are metabolized in the brain is challenging. In an
entire organism, peripheral metabolism produces many of the same metabolites as
those in the brain, and many of these metabolites can cross the blood-brain
barrier from the periphery, thus making the relative contributions of hepatic and
brain metabolism difficult to study in vivo. In addition, drugs and metabolites
contained in ventricles and in the residual blood of capillaries in the brain may
overestimate drugs' and metabolites' concentrations in the brain. In this study,
we examine locusts and zebrafish using matrix assisted laser desorption
ionization mass spectrometry imaging to study brain metabolism and distribution.
These animal models are cost-effective and ethically sound for initial drug
development studies.
PMID- 29350028
TI - Anisotropic Electronic Characteristics, Adsorption, and Stability of Low-Index
BiVO4 Surfaces for Photoelectrochemical Applications.
AB - Many experimental results reveal different activities among different low-index
surfaces of photocatalysts. The current investigation focuses on the theoretical
understanding of the electronic characteristics, surface activity, and stability
of different low-index surfaces of BiVO4 toward water splitting using first
principle calculations. The results indicate that BiVO4 has four types of low
index surfaces, namely, (010)T1, (010)T2, (110)T1, and (111)T1. The different
band edge potentials of the surfaces, resulting from the variation of the
electrostatic potential, lead to a higher oxidation ability for (010)T1 and
(010)T2 than for (110)T1 and (111)T1 surfaces. The electrons prefer to accumulate
on (010)T1 and (010)T2 surfaces, whereas holes like to accumulate on (110)T1 and
(111)T1 surfaces during a photocatalytic process. Moreover, investigation on the
adsorbed intermediates during the water-splitting process indicates that the
oxygen evolution reaction on BiVO4 surfaces is mainly dominated by the reaction
OH* <-> O* + H+ + e-, and (110)T1 and (111)T1 surfaces are energetically more
favorable as photoanodes for water splitting than (010)T1 and (010)T2.
Furthermore, the BiVO4 surface as photoanodes tend to be unstable and can easily
be corroded with or without the presence of an oxidative environment, however,
there is an exception for the BiVO4 (010)T1 and (010)T2 surfaces, which are
thermodynamically stable in the solution when there are no strong oxidative
species. These results provide important insights into the anisotropy behaviors
among low-index surfaces of BiVO4 for photocatalytic reactions.
PMID- 29350030
TI - Correction to "Tunneling Control of Chemical Reactions: The Third Reactivity
Paradigm".
PMID- 29350029
TI - Microwell Array Method for Rapid Generation of Uniform Agarose Droplets and Beads
for Single Molecule Analysis.
AB - Compartmentalization of aqueous samples in uniform emulsion droplets has proven
to be a useful tool for many chemical, biological, and biomedical applications.
Herein, we introduce an array-based emulsification method for rapid and easy
generation of monodisperse agarose-in-oil droplets in a PDMS microwell array. The
microwells are filled with agarose solution, and subsequent addition of hot oil
results in immediate formation of agarose droplets due to the surface-tension of
the liquid solution. Because droplet size is determined solely by the array unit
dimensions, uniform droplets with preselectable diameters ranging from 20 to 100
MUm can be produced with relative standard deviations less than 3.5%. The array
based droplet generation method was used to perform digital PCR for absolute DNA
quantitation. The array-based droplet isolation and sol-gel switching property of
agarose enable formation of stable beads by chilling the droplet array at -20
degrees C, thus, maintaining the monoclonality of each droplet and facilitating
the selective retrieval of desired droplets. The monoclonality of droplets was
demonstrated by DNA sequencing and FACS analysis, suggesting the robustness and
flexibility of the approach for single molecule amplification and analysis. We
believe our approach will lead to new possibilities for a great variety of
applications, such as single-cell gene expression studies, aptamer selection, and
oligonucleotide analysis.
PMID- 29350031
TI - Microbiota-Regulated Outcomes of Human Cancer Immunotherapy via the PD-1/PD-L1
Axis.
PMID- 29350032
TI - Structure and Gas Transport at the Polymer-Zeolite Interface: Insights from
Molecular Dynamics Simulations.
AB - We investigate the structure of polyimide (PI) at the surface of a silicalite
zeolite (MFI), as part of a model hybrid organic-inorganic mixed matrix membrane
system, through equilibrium molecular dynamics simulations. Furthermore, we
report a comparison of the adsorption and transport characteristics of pure
components CO2 and CH4 in PI, MFI, and PI-MFI composite membranes. It is seen
that incorporation of MFI zeolite into PI results in the formation of densified
polymer layers (rigidified region) near the surface, having thickness around 1.2
nm, before bulklike behavior of the polymer is attained, contrary to empirical
fits suggesting the existence of an approximately 1 MUm thick interface between
the polymer and filler. This region offers an extra resistance to gas diffusion
especially for the gas with a larger kinetic diameter, CH4, thus improving the
CO2/CH4 kinetic selectivity in the PI-MFI composite membrane. Furthermore, we
find that the kinetic selectivity of CO2 over CH4 in the rigidified region
increases with temperature and that additivity of transport resistances in MFI,
interfacial layer, and bulklike region of the polymer satisfactorily explains
transport behavior in the composite sandwich investigated. The gas adsorption
isotherms are extracted considering the dynamics and structural transitions in
the PI and PI-MFI composite upon gas adsorption, and it is seen that the
rigidified layer affects the gas adsorption in the polymer in the PI-MFI hybrid
system. A significant increase in CO2/CH4 selectivity as well as gas permeability
is observed in the PI-MFI composite membrane compared to that in the pure PI
polymer membrane, which is correlated with the high selectivity of the rigidified
interfacial layer in the polymer. Thus, while enhancing transport resistance, the
rigidified layer is beneficial to membrane selectivity, leading to improved
performance based on the Robeson upper bound plot for polymers.
PMID- 29350033
TI - Impact of Backbone Pattern and Residue Substitution on Helicity in
alpha/beta/gamma-Peptides.
AB - We have evaluated the impact of changes in the chemical structure of peptidic
oligomers containing alpha-, beta-, and gamma-amino acid residues
(alpha/beta/gamma-peptides) on the propensities of these oligomers to adopt
helical conformations in aqueous and alcoholic solutions. These studies were
inspired by our previous discovery that alpha/beta/gamma-peptides containing a
regular alphagammaalphaalphabetaalpha hexad repeat adopt an alpha-helix-like
conformation in which the beta and gamma residues are aligned in a stripe along
one side, and the remainder of the helix surface is defined by the alpha
residues. This helix was found to be most stable when the beta and gamma residues
were rigidified with specific cyclic constraints. Relaxation of the beta residue
constraints caused profound conformational destabilization, but relaxation of the
gamma residue constraints led to only a moderate drop in helicity. The new work
more broadly characterizes the effect of gamma residue substitution on helix
stability, based on circular dichroism and two-dimensional NMR measurements. We
find that even a fully unsubstituted gamma residue (derived from gamma
aminobutyric acid) supports a moderate helical propensity, which is surprising in
light of the strong destabilizing effect of glycine residues on alpha-helix
stability. Additional studies examine the effects of altering sequence in terms
of amino acid type, by comparing a prototype with the
alphagammaalphaalphabetaalpha hexad pattern to isomers with irregular
arrangements of the alpha, beta, and gamma residues along the backbone. The data
indicate that the strong helix-forming propensity previously discovered for
alpha/beta/gamma-peptide 12-mers is retained when sequence is varied, with small
variations detected across diverse alpha-beta-gamma placements. These structural
findings suggest that alpha/beta/gamma-peptide scaffolds represent versatile
scaffolds for the design of peptidic foldamers that display specific functions.
PMID- 29350034
TI - Probing the Complexities of Structural Changes in Layered Oxide Cathode Materials
for Li-Ion Batteries during Fast Charge-Discharge Cycling and Heating.
AB - The rechargeable lithium-ion battery (LIB) is the most promising energy storage
system to power electric vehicles with high energy density and long cycling life.
However, in order to meet customers' demands for fast charging, the power
performances of current LIBs need to be improved. From the cathode aspect, layer
structured cathode materials are widely used in today's market and will continue
to play important roles in the near future. The high rate capability of layered
cathode materials during charging and discharging is critical to the power
performance of the whole cell and the thermal stability is closely related to the
safety issues. Therefore, the in-depth understanding of structural changes of
layered cathode materials during high rate charging/discharging and the thermal
stability during heating are essential in developing new materials and improving
current materials. Since structural changes take place from the atomic level to
the whole electrode level, combination of characterization techniques covering
multilength scales is quite important. In many cases, this means using
comprehensive tools involving diffraction, spectroscopy, and imaging to
differentiate the surface from the bulk and to obtain structural/chemical
information with different levels of spatial resolution. For example, hard X-ray
spectroscopy can yield the bulk information and soft X-ray spectroscopy can give
the surface information; X-ray based imaging techniques can obtain spatial
resolution of tens of nanometers, and electron-based microcopy can go to
angstroms. In addition to challenges associated with different spatial
resolution, the dynamic nature of structural changes during high rate cycling and
heating requires characterization tools to have the capability of collecting high
quality data in a time-resolved fashion. Thanks to the advancement in synchrotron
based techniques and high-resolution electron microscopy, high temporal and
spatial resolutions can now be achieved. In this Account, we focus on the recent
works studying kinetic and thermal properties of layer-structured cathode
materials, especially the structural changes during high rate cycling and the
thermal stability during heating. Advanced characterization techniques relating
to the rate capability and thermal stability will be introduced. The different
structure evolution behavior of cathode materials cycled at high rate will be
compared with that cycled at low rate. Different response of individual
transition metals and the inhomogeneity in chemical distribution will be
discussed. For the thermal stability, the relationship between structural changes
and oxygen release will be emphatically pointed out. In all these studies being
reviewed, advanced characterization techniques are critically applied to reveal
complexities at multiscale in layer-structured cathode materials.
PMID- 29350035
TI - Selective Proton/Deuteron Transport through Nafion|Graphene|Nafion Sandwich
Structures at High Current Density.
AB - Ion current densities near 1 A cm-2 at modest bias voltages (<200 mV) are
reported for proton and deuteron transmission across single-layer graphene in
polyelectrolyte-membrane (PEM)-style hydrogen pump cells. The graphene is
sandwiched between two Nafion membranes and covers the entire area between two
platinum-carbon electrodes, such that proton transfer is forced to occur through
the graphene layer. Raman spectroscopy confirms that buried graphene layers are
single-layer and relatively free of defects following the hot-press procedure
used to make the sandwich structures. Area-normalized ion conductance values of
approximately 29 and 2.1 S cm-2 are obtained for proton and deuteron transport,
respectively, through single-layer graphene, following correction for
contributions to series resistance from Nafion resistance, contact resistance,
etc. These ion conductance values are several hundred to several thousand times
larger than in previous reports on similar phenomena. A ratio of proton to
deuteron conductance of 14 to 1 is obtained, in good agreement with but slightly
larger than those in prior reports on related cells. Potassium ion transfer rates
were also measured and are attenuated by a factor of many thousands by graphene,
whereas proton transfer is attenuated by graphene by only a small amount. Rates
for hydrogen and deuterium ion exchange across graphene were analyzed using a
model whereby each hexagonal graphene hollow site is assumed to transmit ions
with a specific per-site ion-transfer self-exchange rate constant. Rate constant
values of approximately 2500 s-1 for proton transfer and 180 s-1 for deuteron
transfer per site through graphene are reported.
PMID- 29350036
TI - Electrochemical and Spectral Characterization of Iron Corroles in High and Low
Oxidation States: First Structural Characterization of an Iron(IV) Tetrapyrrole
pi Cation Radical.
AB - The electrochemistry and spectroscopic properties of three iron corroles were
examined in benzonitrile, dichloromethane, and pyridine containing 0.1 M tetra-n
butylammonium perchlorate or tetra-n-ethylammonium hexafluorophosphate as
supporting electrolyte. The investigated compounds are represented as
(OEC)FeIV(C6H5), (OEC)FeIVCl, and (OEC)FeIII(py), where OEC is the trianion of
2,3,7,8,12,13,17,18-octaethylcorrole. Each iron(IV) corrole undergoes two one
electron reductions and two or three one-electron oxidations depending upon the
solvent. Under the same solution conditions, the iron(III) corrole undergoes a
single one-electron reduction and one or two one-electron oxidations. Each singly
oxidized and singly reduced product was characterized by UV-vis and/or EPR
spectroscopy. The data indicate a conversion of (OEC)FeIV(C6H5) and (OEC)FeIVCl
to their iron(III) forms upon a one-electron reduction and to iron(IV) corrole pi
cation radicals upon a one-electron oxidation. The metal center in
[(OEC)FeIII(C6H5)]- is low spin (S = 1/2) as compared to electrogenerated
[(OEC)FeIIICl]-, which contains an intermediate-spin (S = 3/2) iron(III).
(OEC)FeIII(py) also contains an intermediate-spin-state iron(III) and, unlike
previously characterized (OEC)FeIII(NO), is converted to an iron(IV) corrole upon
oxidation rather than to an iron(III) pi cation radical. Singly oxidized
[(OEC)FeIV(C6H5)]*+ is the first iron(IV) tetrapyrrole pi cation radical to be
isolated and was structurally characterized as a perchlorate salt. It
crystallizes in the triclinic space group P1 with a = 10.783(3) A, b = 13.826(3)
A, c = 14.151(3) A, alpha = 78.95(2) degrees , beta = 89.59(2) degrees , and
gamma = 72.98(2) degrees at 293 K with Z = 2. Refinement of 8400 reflections and
670 parameters against F o2 yields R1 = 0.0864 and wR2 = 0.2293. The complex
contains a five-coordinated iron with average Fe-N bond lengths of 1.871(3) A.
The formulation of the electron distribution in this compound was confirmed by
Mossbauer, X-ray crystallographic, and magnetic susceptibility data as well as by
EPR spectroscopy, which gives evidence for strong antiferromagnetic coupling
between the iron(IV) center and the singly oxidized corrole macrocycle.
PMID- 29350037
TI - Oxidation of Isodiphenylfluorindine: Routes to 13-Oxoisodiphenylfluorindinium
Perchlorate and Fluorindine Cruciform Dimers.
AB - Isodiphenylfluorindine (5) reacts with K2Cr2O7/H+ to give 13
oxoisodiphenylfluorindinium perchlorate (7) (75%), but with phenyliodine
bis(trifluoroacetate) (PIFA) or MnO2 it gives the zwitterionic and quinoidal
cruciform 13,13'-dimers 11 (85%) and 12 (89%), respectively. The zwitterionic
13,13'-dimer 11 can be rapidly converted with MnO2 into the quinoidal 13,13'
dimer 12 (100%). UV-vis, NMR, single-crystal X-ray diffraction, and density
functional theory studies support the structural assignments of all products. The
electrochemical behavior of the compounds is also presented.
PMID- 29350038
TI - Efficient Mass Spectral Analysis of Active Transporters Overexpressed in
Escherichia coli.
AB - Structural analysis of purified active membrane proteins can be performed by mass
spectrometry (MS). However, no large-scale expression systems for active
eukaryotic membrane proteins are available. Moreover, because membrane proteins
cannot easily be digested by trypsin and ionized, they are difficult to analyze
by MS. We developed a method for mass spectral analysis of eukaryotic membrane
proteins combined with an overexpression system in Escherichia coli. Vesicular
glutamate transporter 2 (VGLUT2/SLC17A6) with a soluble alpha-helical protein and
histidine tag on the N- and C-terminus, respectively, was overexpressed in E.
coli, solubilized with detergent, and purified by Ni-NTA affinity chromatography.
Proteoliposomes containing VGLUT2 retained glutamate transport activity. For MS
analysis, the detergent was removed from purified VGLUT2 by trichloroacetic acid
precipitation, and VGLUT2 was then subjected to reductive alkylation and tryptic
digestion. The resulting peptides were detected with 88% coverage by matrix
assisted laser desorption ionization time-of-flight (MALDI-TOF) MS with or
without liquid chromatography. Vesicular excitatory amino acid transporter and
vesicular acetylcholine transporter were also detected with similar coverage by
the same method. Thus this methodology could be used to analyze purified
eukaryotic active transporters. Structural analysis with chemical modifiers by MS
could have applications in functional binding analysis for drug discovery.
PMID- 29350039
TI - Rhodium(III)-Catalyzed Directed C-H Coupling with Methyl Trifluoroacrylate:
Diverse Synthesis of Fluoroalkenes and Heterocycles.
AB - An example of Rh-catalyzed C-H activation with methyl trifluoroacrylate for the
synthesis of fluoroolefins and heterocycles (benzoindolizines) is reported. The
types of products were determined by the directing group. The benzoindolizines
and fluoroolefins were obtained by using pyridine and pyrazole as the directing
group, correspondingly. These transformations present a number of advantages,
such as oxidant-free reaction conditions and broad functional group tolerance.
Moreover, this reaction greatly extends the application of fluoroolefins.
PMID- 29350041
TI - Chemo-, Regio-, and Enantioselective Rhodium-Catalyzed Allylation of Triazoles
with Internal Alkynes and Terminal Allenes.
AB - The rhodium-catalyzed asymmetric N1-selective and regioselective coupling of
triazole derivatives with internal alkynes and terminal allenes gives access to
secondary and tertiary allylic triazoles in very good enantioselectivities. For
this process, three new members of the JosPOphos ligand family have been prepared
and employed in catalysis. The optimized reaction conditions enable the coupling
of triazoles with internal alkynes as well as with allenes, displaying a high
tolerance for functional groups. A gram scale reaction provided N1-allyltriazole,
which was subjected to various transformations highlighting synthetic utility.
PMID- 29350040
TI - Formal (4 + 1)-Addition of Allenoates to o-Quinone Methides.
AB - The first (4 + 1)-annulation of o-quinone methides with alpha-branched allenoates
as C1 synthons has been developed. This operationally simple protocol gives
access to highly functionalized dihydrobenzofurans in an unprecedented fashion
with excellent diastereoselectivities and high yields.
PMID- 29350042
TI - Application of Sulfur Ylides in 1,2-Difunctionalization of Arynes via Insertion
into a C-S sigma-Bond.
AB - A novel reactivity of sulfur ylides has been demonstrated in a transition-metal
free protocol to access ortho-substituted thioanisole derivatives by insertion of
arynes into a C-S sigma-bond in moderate to good yields. The reaction involves
the formation of C-C and C-S bonds and consecutive breaking of two C-S bonds
under operationally mild reaction conditions.
PMID- 29350043
TI - The Acid-Free Cyclopropanol-Minisci Reaction Reveals the Catalytic Role of Silver
Pyridine Complexes.
AB - A well-defined homogeneous silver precatalyst can be utilized for the direct C-H
functionalization of a wide range of aromatic nitrogen heterocycles with
cyclopropanols under acid-free conditions. This reaction can be conducted on gram
scale and with low catalyst loadings (as low as 1%), which is rare for silver
catalyzed Minisci-type reactions. Moreover, reactivity trends, as well as steric
and calculated electronic properties of the heterocycles, strongly suggest that
silver-heterocycle complexes formed in situ behave as redox active catalysts and
as Lewis acid activators of the heterocycle and that the electronic nature of the
heterocyclic substrates tunes the reactivity of the resulting complexes.
PMID- 29350044
TI - Enhanced Thermal Stability in Perovskite Solar Cells by Assembling 2D/3D Stacking
Structures.
AB - Two-dimensional (2D) perovskites have been shown to be more stable than their
three-dimensional (3D) counterparts due to the protection of the organic ligands.
Herein a method is introduced to form 2D/3D stacking structures by the reaction
of 3D perovskite with n-Butylamine (BA). Different from regular treatment with n
Butylammonium iodide (BAI) where 2D perovskite with various layers form, the
reaction of BA with MAPbI3 only produce (BA)2PbI4, which has better protection
due to more organic ligands in (BA)2PbI4 than the mixture of 2D perovskites.
Compared to BAI treatment, BA treatment results in smoother 2D perovskite layer
on 3D perovskites with a better coverage. The photovoltaic devices with 2D/3D
stacking structures show much improved stability in comparison to their 3D
counterparts when subjected to heat stress tests. Moreover, the conversion of
defective surface into 2D layers also induces passivation of the 3D perovskites
resulting in an enhanced efficiency.
PMID- 29350045
TI - Total Synthesis of (-)-Xestosaprol N and O.
AB - The first total synthesis of (-)-xestosaprol N and O is described. This synthetic
work features a convergent strategy: (1) a Pd-catalyzed arylation followed by
cyclization to build a naphthalene fragment (ring C, D); (2) utilization of (-)
quinic acid to construct the chiral hydroxyl group at C-2; (3) a substrate
controlled intramolecular Heck reaction to construct a quaternary carbon center
(ring B); (4) introduction of a hypotaurine moiety at a late stage to furnish the
E ring.
PMID- 29350046
TI - Catalytic Enantioselective Reaction of 2H-Azirines with Thiols Using Cinchona
Alkaloid Sulfonamide Catalysts.
AB - The first catalytic enantioselective reaction of 2H-azirines with thiols has been
developed. The obtained aziridines can be converted to optically active
oxazolines, aziridylamides, or alpha-sulfonyl esters. Transformation of these
optically active aziridines showed that 2H-azirines act as beta,beta
dicarbocationic amine synthons.
PMID- 29350047
TI - Removable Water-Soluble Olefin Metathesis Catalyst via Host-Guest Interaction.
AB - A highly removable N-heterocyclic carbene ligand for a transition-metal catalyst
in aqueous media via host-guest interactions has been developed. Water-soluble
adamantyl tethered ethylene glycol in the ligand leads a hydrophobic inclusion
into the cavity of beta-cyclodextrin. Ruthenium (Ru) olefin metathesis catalyst
with this ligand demonstrated excellent performance in various metathesis
reactions in water as well as in CH2Cl2, and removal of residual Ru was performed
via filtration utilizing a host-guest interaction and extraction.
PMID- 29350048
TI - Triple-split-bolus versus single-bolus CT in abdominal trauma patients: a
comparative study.
AB - Background Split-bolus computed tomography (CT) is a recent development in trauma
imaging. Instead of multiple scans in different contrast phases after a single
contrast bolus, split-bolus protocols consist of one single scan of the thorax
and abdomen after two or three contrast injections at different points of time.
Purpose To evaluate and compare image quality and injury findings of a new triple
split-bolus CT (TS-CT) protocol of thorax and abdomen with those of a portal
venous phase CT (PV-CT) in the same patient group. Material and Methods Trauma
patients in 2009-2012 who underwent both the TS-CT initially and a PV-CT during
the next six weeks were included. The TS-CT examination was performed as one CT
run after application of three contrast boluses (total 175 mL) to enhance renal
pelvis and urinary tract, the abdominal organs, and the large arterial vessels.
The PV-CT had a fixed delay of 85 s. We measured attenuation in Hounsfield units
(HU), evaluated possible organ injury and assessed image quality on a 5-point
scale. Results Thirty-five patients were included. Attenuation measurements of
major abdominal vessels, organs, and renal pelvis were significantly higher with
the TS-CT protocol. Performance in organ injury diagnosis and image quality was
equal in both protocols. Conclusion The overall performance of the TS-CT protocol
is similar to the standard PV-CT. Excellent visualization of the arterial tree
and the collecting system may eliminate the need for separate scans.
PMID- 29350050
TI - Marital Status and Trajectories of Depressive Symptoms Among Older Adults of
Mexican Descent.
AB - Little is known about the implications of marital status for the age patterning
of depressive symptoms in later life. Drawing on seven waves of data from the
Hispanic Established Population for the Epidemiologic Study of the Elderly, this
research uses growth curve models to examine age trajectories of depressive
symptoms among continuously married and recently and continuously widowed older
adults of Mexican descent (aged 65 years and older; N = 1,452). The findings
demonstrate that despite having a higher mean level of depressive symptoms, the
recently widowed experienced a similar rate of increase in distress with age to
that of their married counterparts. Compared with the married, the continuously
widowed had a steeper rise in depressive symptoms with age, although they had
fewer symptoms at younger ages in later life. Physical health, financial strain,
social support, and church attendance might account to a certain extent for
marital status differences in depressive symptoms across later life.
PMID- 29350052
TI - Protective mechanisms of 6-gingerol in dextran sulfate sodium-induced chronic
ulcerative colitis in mice.
AB - Ulcerative colitis (UC) is a relapsing and remitting inflammatory disease of the
colon, with an increasing incidence worldwide. 6-Gingerol (6G) is a bioactive
constituent of Zingiber officinale, which has been reported to possess various
biological activities. This study was designed to evaluate the role of 6G in
chronic UC. Chronic UC was induced in mice by three cycles of 2.5% dextran
sulfate sodium (DSS) in drinking water. Each cycle consisted of 7 days of 2.5%
DSS followed by 14 days of normal drinking water. 6G (100 mg/kg) and a reference
anti-colitis drug sulfasalazine (SZ) (100 mg/kg) were orally administered daily
to the mice throughout exposure to three cycles of 2.5% DSS. Administration of 6G
and SZ significantly prevented disease activity index and aberrant crypt foci
formation in DSS-treated mice. Furthermore, 6G and SZ suppresses immunoexpression
of tumor necrosis factor alpha, interleukin-1beta, inducible nitric oxide
synthase, Regulated on activation, normal T cell expressed and secreted (RANTES),
and Monocyte chemoattractant protein-1 (MCP-1) in the DSS-treated mice. 6G
effectively protected against colonic oxidative damage by augmenting the
antioxidant status with marked decrease in lipid peroxidation levels in DSS
treated mice. Moreover, 6G significantly inhibited nuclear factor kappa B (P65),
p38, cyclooxygenase-2, and beta-catenin whereas it enhanced IL-10 and adenomatous
polyposis coli expression in DSS-treated mice. In conclusion, 6G prevented DSS
induced chronic UC via anti-inflammatory and antioxidative mechanisms and
preservation of the Wnt/beta-catenin signaling pathway.
PMID- 29350051
TI - HSA-based multi-target combination therapy: regulating drugs' release from HSA
and overcoming single drug resistance in a breast cancer model.
AB - Multi-drug delivery systems, which may be promising solution to overcome
obstacles, have limited the clinical success of multi-drug combination therapies
to treat cancer. To this end, we used three different anticancer agents,
Cu(BpT)Br, NAMI-A, and doxorubicin (DOX), to build human serum albumin (HSA)
based multi-drug delivery systems in a breast cancer model to investigate the
therapeutic efficacy of overcoming single drug (DOX) resistance to cancer cells
in vivo, and to regulate the drugs' release from HSA. The HSA complex structure
revealed that NAMI-A and Cu(BpT)Br bind to the IB and IIA sub-domain of HSA by N
donor residue replacing a leaving group and coordinating to their metal centers,
respectively. The MALDI-TOF mass spectra demonstrated that one DOX molecule is
conjugated with lysine of HSA by a pH-sensitive linker. Furthermore, the release
behavior of three agents form HSA can be regulated at different pH levels.
Importantly, in vivo results revealed that the HSA-NAMI-A-Cu(BpT)Br-DOX complex
not only increases the targeting ability compared with a combination of the three
agents (the NAMI-A/Cu(BpT)Br/DOX mixture), but it also overcomes DOX resistance
to drug-resistant breast cancer cell lines.
PMID- 29350053
TI - 8-isopentenyl isoflavone derivatives from the whole herb of Sphaerophysa salsula.
AB - Phytochemical studies on the whole herb of Sphaerophysa salsula has resulted in
the discovery of one new 8-isopentenyl isoflavone derivative, named sphaerosin s2
(3-(8-(2-hydroxypropan-2-yl)-3,4-dihydro-2H-furo[2,3-h]chromen-3-yl)-2,6
dimethoxyphenol) (1), along with four know 8-isopentenyl isoflavone derivatives
(2-5). Compounds (2, 4 and 5) were isolated for the first time from this species.
Their structures were elucidated on the basis of ESI-MS, UV, IR, 1D NMR and 2D
NMR data.
PMID- 29350054
TI - Caloinophyllin A, a new chromanone derivative from Calophyllum inophyllum roots.
AB - A new chromanone derivative, namely caloinophyllin A (1), along with eight known
compounds (2-9), nobiletin (2), pentamethylquercetin (3), 3,5,7,4'
tetramethoxyflavone (4), 5,7,4'-trimethoxyflavone (5), 1,5-dihydroxyxanthone (6),
1,8-dimethoxy-2-hydroxyxanthone (7), 1,6-dihydroxy-7-methoxyxanthone (8) and 4
methoxycaffeic acid (9) were isolated from the roots of Calophyllum inophyllum.
The structures of all the isolated compounds (1-9) were fully characterised using
spectroscopic data, as well as comparison with the previous literature data. In
addition, the quantum chemical calculation has been used to confirm the
conformation of 1. Moreover, all isolated compounds were assessed for their in
vitro cytotoxicity against five human cancer cell lines.
PMID- 29350049
TI - Targeted and Off-Target (Bystander and Abscopal) Effects of Radiation Therapy:
Redox Mechanisms and Risk/Benefit Analysis.
AB - SIGNIFICANCE: Radiation therapy (from external beams to unsealed and sealed
radionuclide sources) takes advantage of the detrimental effects of the clustered
production of radicals and reactive oxygen species (ROS). Research has mainly
focused on the interaction of radiation with water, which is the major
constituent of living beings, and with nuclear DNA, which contains the genetic
information. This led to the so-called target theory according to which cells
have to be hit by ionizing particles to elicit an important biological response,
including cell death. In cancer therapy, the Poisson law and linear quadratic
mathematical models have been used to describe the probability of hits per cell
as a function of the radiation dose. Recent Advances: However, in the last 20
years, many studies have shown that radiation generates "danger" signals that
propagate from irradiated to nonirradiated cells, leading to bystander and other
off-target effects. CRITICAL ISSUES: Like for targeted effects, redox mechanisms
play a key role also in off-target effects through transmission of ROS and
reactive nitrogen species (RNS), and also of cytokines, ATP, and extracellular
DNA. Particularly, nuclear factor kappa B is essential for triggering self
sustained production of ROS and RNS, thus making the bystander response similar
to inflammation. In some therapeutic cases, this phenomenon is associated with
recruitment of immune cells that are involved in distant irradiation effects
(called "away-from-target" i.e., abscopal effects). FUTURE DIRECTIONS:
Determining the contribution of targeted and off-target effects in the clinic is
still challenging. This has important consequences not only in radiotherapy but
also possibly in diagnostic procedures and in radiation protection.
PMID- 29350056
TI - New isolates from leaves of Nicotiana tabacum and their biological activities.
AB - Three new isolates (1-3) including one new sterol and two new flavonoids together
with three known sterols (4-6) were isolated from the leaves of Nicotiana
tabacum. Their structures were determined mainly by spectroscopic methods,
including extensive 1D and 2D NMR techniques. All compounds were evaluated for
their anti-tobacco mosaic virus and cytotoxic activities. The results showed that
compounds 2 and 3 exhibited high anti-TMV activity with inhibition rate of 34.2
and 33.4%, respectively, which were roughly equivalent to that of positive
control. The cytotoxicities of compounds 1 and 4-6 against five human tumour cell
lines were also tested, and tested compounds showed weak inhibitory activities
against some tested human tumour cell lines.
PMID- 29350057
TI - Comment on 'Effect of marijuana use on cardiovascular and cerebrovascular
mortality'.
PMID- 29350058
TI - The challenge of risk prediction: How good are we?
PMID- 29350055
TI - Therapeutic strategies and nano-drug delivery applications in management of
ageing Alzheimer's disease.
AB - In recent years, the incidental rate of neurodegenerative disorders has increased
proportionately with the aging population. Alzheimer's disease (AD) is one of the
most commonly reported neurodegenerative disorders, and it is estimated to
increase by roughly 30% among the aged population. In spite of screening numerous
drug candidates against various molecular targets of AD, only a few candidates -
such as acetylcholinesterase inhibitors are currently utilized as an effective
clinical therapy. However, targeted drug delivery of these drugs to the central
nervous system (CNS) exhibits several limitations including meager solubility,
low bioavailability, and reduced efficiency due to the impediments of the blood
brain barrier (BBB). Current advances in nanotechnology present opportunities to
overcome such limitations in delivering active drug candidates. Nanodrug delivery
systems are promising in targeting several therapeutic moieties by easing the
penetration of drug molecules across the CNS and improving their bioavailability.
Recently, a wide range of nano-carriers, such as polymers, emulsions, lipo
carriers, solid lipid carriers, carbon nanotubes, metal based carriers etc., have
been adapted to develop successful therapeutics with sustained release and
improved efficacy. Here, we discuss few recently updated nano-drug delivery
applications that have been adapted in the field of AD therapeutics, and future
prospects on potential molecular targets for nano-drug delivery systems.
PMID- 29350059
TI - A new curriculum to address dementia-related stigma: Preliminary experience with
Alzheimer's Association staff.
AB - Objective Develop and test a stigma awareness and education curriculum targeted
to non-medical staff of a local Alzheimer's Association chapter. Methods The
curriculum, developed in collaboration with leadership and educational staff from
the Cleveland Chapter of the Alzheimer's Association, included a definition,
types, and domains of stigma; effects of stigma on individuals with dementia and
their families; stigma evaluation studies; tips to address the topic of dementia
related stigma with individuals and families. Lastly, an interactive discussion
of real-life scenarios facilitated stigma recognition and management. Results
Most staff felt the training improved their ability to identify Alzheimer's
disease stigma, made them more comfortable talking about stigma, and would change
the way they interacted with people and families impacted by Alzheimer's disease.
Conclusions This brief, practical educational curriculum has potential to improve
awareness of dementia stigma in Alzheimer's Association staff. Research is needed
to expand stigma awareness in individuals and groups with varying levels of
dementia knowledge.
PMID- 29350060
TI - "So they are not alive?": Dementia, reality disjunctions and conversational
strategies.
AB - In some conversations involving persons with Alzheimer's disease, the
participants may have to deal with the difficulty that they do not share a common
ground in terms of not only who is alive or dead, but even more, who could
possibly be alive. It is as if the participants face a reality disjunction. There
are very few empirical studies of this difficulty in conversations involving
persons with Alzheimer's disease or other kinds of dementia diagnoses. Often
studies of confabulation have a focus on the behavior and experience of the
healthy participants, but rarely on the interaction and the collaborative
contributions made by the person with dementia. In the present article, we
discuss various strategies used by all participants in an everyday conversation.
The material consists of an hour long everyday conversation between a woman with
Alzheimer's disease and two healthy participants (relatives). This conversation
is analyzed by looking at the organization of the interaction with an emphasis on
how the participants deal with instances of reality disjunctions. The result from
the analysis demonstrates that both the healthy participants as well as the
person with dementia together skillfully avoid the face threats posed by reality
disjunctive contributions by not pursuing argumentative lines that in the end
might jeopardize both the collaborative and the personal relations.
PMID- 29350062
TI - Telotristat ethyl: a novel agent for the therapy of carcinoid syndrome diarrhea.
AB - Carcinoid syndrome (CS), characterized by diarrhea and flushing, is present in
20% of patients with neuroendocrine tumors at diagnosis and becomes more frequent
with progression. The diarrhea of CS is caused mainly by tumoral secretion of
serotonin. It may not be fully controlled by somatostatin analogs, the currently
indicated drugs for symptomatic relief. Telotristat ethyl is a novel inhibitor of
tryptophan hydroxylase, the rate-limiting enzyme in serotonin biosynthesis.
Administration of the drug decreases diarrhea in patients with CS. Telotristat
ethyl was approved in February 2017 (USA) and September 2017 (European
Commission) for the treatment of CS diarrhea in adults inadequately controlled by
somatostatin analog alone. This drug is expected to greatly improve the health
and quality of life of patients with CS diarrhea.
PMID- 29350063
TI - A qualitative interview study of people living with well-controlled Type 1
diabetes.
AB - OBJECTIVE: While many people with Type 1 diabetes find it difficult to achieve
recommended blood glucose levels, a minority do achieve good control. Our study
was conceived by patient and public (PP) partners and sought to learn about
experiences of people living with well-controlled diabetes. DESIGN: A
collaboration between academic health psychologists and five PP partners with
experience of diabetes, who were trained to conduct and analyse semi-structured
interviews. Fifteen adults with well-controlled Type 1 diabetes were interviewed
about the history of their diabetes and their current self-management practices.
Interviews were subjected to inductive thematic analysis. RESULTS: Eight sub
themes were arranged into two overarching themes, 'facing up to diabetes' and
'balance leads to freedom'. Participants described a process of acceptance and
mastery of diabetes, and talked about how they gained a deeper understanding of
bodily processes through trial and error. CONCLUSION: Based on the experiences of
people with well-controlled Type 1 diabetes, interventions for people with this
condition should encourage acceptance of the diagnosis and increasing confidence
to experiment with behaviours (trial and error) to encourage 'mastery' of self
management. The research collaboration described here is an example of best
practice for future researchers wanting to actively engage PP partners.
PMID- 29350064
TI - Comparison of hyaluronic acid-based micelles and polyethylene glycol-based
micelles on reversal of multidrug resistance and enhanced anticancer efficacy in
vitro and in vivo.
AB - Polyethylene glycol (PEG)-based block copolymer micelles and hyaluronic acid (HA)
based grafted copolymer micelles have been widely investigated in chemotherapy.
In this study, to evaluate the differences among HA-based grafted polymer
micelles, PEG-based block polymer micelles and the mixed of these two micelles in
enhancing antitumor effects and overcoming MDR, two amphiphilic vitamin E
succinate (VES) derivatives, HA VES (HA-g-VES) and PEG 2000 VES (TPGS2k), were
applied as nanocarriers to prepare HA-VES micelles (HA-PMs), TPGS2k micelles
(TPGS2k-PMs) and the mixed micelles (HA/TPGS2k-PMs) for the co-delivery of
doxorubicin (DOX) and curcumin (Cur). With the addition of TPGS2k, the particle
size of HA/TPGS2k-PMs (153.37 +/- 1.00 nm) was smaller than that of HA-PMs
(223.83 +/- 1.84) but significantly larger than that of TPGS2k-PMs (about 20 nm).
The loading efficiency of HA/TPGS2k-PMs was 7.10%, which was lower than HA-PMs
(8.31 +/- 0.15%) but higher than TPGS2k-PMs (4.38 +/- 0.24%). In vitro, HA/TPGS2k
PMs and TPGS2k-PMs exhibited higher cytotoxicity and reversal MDR effects than HA
PMs in MCF-7/Adr cells. However, HA/TPGS2k-PMs, HA-PMs and TPGS2k-PMs all
significantly improved the tumor biodistribution, the antitumor effects and
reduced the side effects of DOX in 4T1-tumor-bearing mice, but these three
micelles displayed no differences in vivo. Therefore, EPR passive targeting
effects caused by PEGylated micelles and CD44 active targeting effects caused by
HA-based micelles have no significant variance in the delivery of antitumor drugs
by i.v.
PMID- 29350065
TI - Molecular typing of Lactobacillus brevis isolates from Korean food using
repetitive element-polymerase chain reaction.
AB - Lactobacillus brevis is a part of a large family of lactic acid bacteria that are
present in cheese, sauerkraut, sourdough, silage, cow manure, feces, and the
intestinal tract of humans and rats. It finds its use in food fermentation, and
so is considered a "generally regarded as safe" organism. L. brevis strains are
extensively used as probiotics and hence, there is a need for identifying and
characterizing these strains. For identification and discrimination of the
bacterial species at the subspecific level, repetitive element-polymerase chain
reaction method is a reliable genomic fingerprinting tool. The objective of the
present study was to characterize 13 strains of L. brevis isolated from various
fermented foods using repetitive element-polymerase chain reaction. Repetitive
element-polymerase chain reaction was performed using three primer sets, REP,
Enterobacterial Repetitive Intergenic Consensus (ERIC), and (GTG)5, which
produced different fingerprinting patterns that enable us to distinguish between
the closely related strains. Fingerprinting patterns generated band range in
between 150 and 5000 bp with REP, 200-7500 bp with ERIC, and 250-2000 bp with
(GTG)5 primers, respectively. The Jaccard's dissimilarity matrices were used to
obtain dendrograms by the unweighted neighbor-joining method using genetic
dissimilarities based on repetitive element-polymerase chain reaction
fingerprinting data. Repetitive element-polymerase chain reaction proved to be a
rapid and easy method that can produce reliable results in L. brevis species.
PMID- 29350061
TI - The Adverse Effects of Environmental Noise Exposure on Oxidative Stress and
Cardiovascular Risk.
AB - Epidemiological studies have provided evidence that traffic noise exposure is
linked to cardiovascular diseases such as arterial hypertension, myocardial
infarction, and stroke. Noise is a nonspecific stressor that activates the
autonomous nervous system and endocrine signaling. According to the noise
reaction model introduced by Babisch and colleagues, chronic low levels of noise
can cause so-called nonauditory effects, such as disturbances of activity, sleep,
and communication, which can trigger a number of emotional responses, including
annoyance and subsequent stress. Chronic stress in turn is associated with
cardiovascular risk factors, comprising increased blood pressure and
dyslipidemia, increased blood viscosity and blood glucose, and activation of
blood clotting factors, in animal models and humans. Persistent chronic noise
exposure increases the risk of cardiometabolic diseases, including arterial
hypertension, coronary artery disease, diabetes mellitus type 2, and stroke.
Recently, we demonstrated that aircraft noise exposure during nighttime can
induce endothelial dysfunction in healthy subjects and is even more pronounced in
coronary artery disease patients. Importantly, impaired endothelial function was
ameliorated by acute oral treatment with the antioxidant vitamin C, suggesting
that excessive production of reactive oxygen species contributes to this
phenomenon. More recently, we introduced a novel animal model of aircraft noise
exposure characterizing the underlying molecular mechanisms leading to noise
dependent adverse oxidative stress-related effects on the vasculature. With the
present review, we want to provide an overview of epidemiological, translational
clinical, and preclinical noise research addressing the nonauditory, adverse
effects of noise exposure with focus on oxidative stress. Antioxid. Redox Signal.
28, 873-908.
PMID- 29350066
TI - Differential expression of cytokeratin 14 and 18 in bladder cancer tumorigenesis.
AB - It has been previously suggested that cytokeratins (CKs) are important diagnostic
and prognostic biomarkers for urothelial lesions. Hence it is imperative to
understand the expression pattern of cytokeratins during formation of papillary
bladder cancer, which was the objective of the current study. Expression pattern
of CK14 and CK18 were examined using immunohistochemical staining in a mice model
of papillary bladder cancer. Twenty female mice were divided into two groups
group 1 (NT) and group 2, which received N-butyl- N-(4-hydroxybutyl) nitrosamine
(BBN) for 20 weeks plus one week without treatment. Following histological
classification of bladder lesions, CK14 and CK18 immunostaining was assessed
according to its distribution and intensity. In NT animals, both basal cells and
umbrella cells showed sporadic positive staining for CK14 and CK18, respectively.
In BBN group, hyperplastic lesions showed significantly more CK14 and
significantly less CK18 staining ( P < 0.05 in each case). Invasive carcinomas
showed increased CK14 immunostaining in all epithelial layers. Cumulatively, our
data indicate that altered CK14 (high) and CK18 (low) expression is perhaps an
early event in bladder cancer tumorigenesis in females at least and is
characteristic of both urothelial superficial pre-neoplastic and neoplastic
lesions. Impact statement Studies have shown that expression of cytokeratins
(CKs) or their altered distribution affects the bladder cancer pathogenesis and
disease outcome, while the underlying mechanisms are not clear. The present study
aims to explore the expression pattern of CK14 and CK18 during formation of
papillary bladder cancer. The results showed that hyperplastic lesions showed
significantly more CK14 and significantly less CK18 staining and invasive
carcinomas showed increased CK14 immunostaining in all epithelial layers in N
butyl- N-(4-hydroxybutyl)nitrosamine (BBN)-induced mouse model. The results
indicate that altered CK14 (high) and CK18 (low) expression is perhaps an early
event in bladder cancer tumorigenesis and is characteristic of both urothelial
superficial pre-neoplastic and neoplastic lesions, which may provide the early
diagnosis index.
PMID- 29350067
TI - Soluble Neuregulin1 is strongly up-regulated in the rat model of Charcot-Marie
Tooth 1A disease.
AB - Neuregulin1 (NRG1) is a growth factor playing a pivotal role in peripheral nerve
development through the activation of the transmembrane co-receptors ErbB2-ErbB3.
Soluble NRG1 isoforms, mainly secreted by Schwann cells, are strongly and
transiently up-regulated after acute peripheral nerve injury, thus suggesting
that they play a crucial role also in the response to nerve damage. Here we show
that in the rat experimental model of the peripheral demyelinating neuropathy
Charcot-Marie-Tooth 1A (CMT1A) the expression of the different NRG1 isoforms
(soluble, type alpha and beta, type a and b) is strongly up-regulated, as well as
the expression of NRG1 co-receptors ErbB2-ErbB3, thus showing that CMT1A nerves
have a gene expression pattern highly reminiscent of injured nerves. Because it
has been shown that high concentrations of soluble NRG1 negatively affect
myelination, we suggest that soluble NRG1 over-expression might play a negative
role in the pathogenesis of CMT1A disease, and that a therapeutic approach, aimed
to interfere with NRG1 activity, might be beneficial for CMT1A patients. Further
studies will be necessary to test this hypothesis in animal models and to
evaluate NRG1 expression in human patients. Impact statement Charcot-Marie
Tooth1A (CMT1A) is one of the most frequent inherited neurological diseases,
characterized by chronic demyelination of peripheral nerves, for which effective
therapies are not yet available. It has been recently proposed that the treatment
with soluble Neuregulin1 (NRG1), a growth factor released by Schwann cells
immediately after acute nerve injury, might be effective in CMT1A treatment.
However, the expression of the different isoforms of endogenous NRG1 in CMT1A
nerves has not been yet investigated. In this preliminary study, we demonstrate
that different isoforms of soluble NRG1 are strongly over-expressed in CMT1A
nerves, thus suggesting that a therapeutic approach based on NRG1 treatment
should be carefully reconsidered. If soluble NRG1 is over-expressed also in human
CMT1A nerves, a therapeutic approach aimed to inhibit (instead of stimulate) the
signal transduction pathways driven by NRG1 might be fruitfully developed.
Further studies will be necessary to test these hypotheses.
PMID- 29350069
TI - New and developing pharmacotherapy for osteoporosis in men.
AB - INTRODUCTION: Osteoporosis represents a major health and societal burden in men,
as well as in women. However, only a minority of men are screened and treated for
osteoporosis and fracture prevention, even after first fracture. Areas covered:
This article provides a comprehensive summary of the currently available drugs
for osteoporosis in men as well as insights into new and developing
pharmacotherapy. Expert opinion: To date, therapeutic approaches to osteoporosis
in men remain not as well defined as in women, since antifracture efficacy data
are lacking for most approved pharmaceuticals. Based on the currently available
evidence, bisphosphonates are generally recommended as first line pharmacotherapy
in men. Conceptually, osteoanabolic agents, such as teriparatide could be more
appropriate for men with primary osteoporosis and low bone turnover. However,
osteoanabolic agents display a limited anabolic window during which their
stimulatory effects on bone formation prevail over the increase in bone
resorption and their use, for theoretical safety reasons, is limited to a
cumulative duration of two years. Due to the recent advances in bone biology,
future drugs for osteoporosis in men might include more selective antiresorptive
compounds which do not markedly inhibit bone formation as well as newer
osteoanabolic agents that appear to more selectively stimulate bone formation.
PMID- 29350070
TI - Celiac antibodies in children with type 1 diabetes - A diagnostic validation
study.
AB - INTRODUCTION: Autoimmune diseases, such as celiac disease (CD) and diabetes
mellitus type 1, tend to co-occur within the same patient. The prevalence of CD
in diabetic children is higher than in the general population, and is estimated
to be 0.6-16.4%. The diagnosis of CD is based on histopathological examination
and serological testing, however, these methods are still imperfect and new
diagnostic algorithms should be considered. AIM: The aim of the study was to
assess the diagnostic value of serological tests detecting antibodies against
deamidated gliadin peptide, endomysium, tissue transglutaminase, neo-epitope
tissue transglutaminase and to identify HLA-related genetic predisposition to CD
in patients with type 1 diabetes mellitus (DM1). METHODS: Autoantibodies were
measured in the sera of 392 children suffering from DM1 aged 1-19 years old (mean
11.76 +/- 4.14 years old). Additionally, PCR-based assessment of HLA DQ2/DQ8
genotyping was performed. RESULTS: A positive result of at least one serological
test was obtained from 81 children (20.66%). The sensitivity and specificity were
76.47% and 91.67% for anti-DGP IgA, 70.59% and 58.33% for IgG anti-DGP,
respectively. A positive predictive value was 100% for the anti-TG IgA at cutoff
levels of 5 and 10 times higher than upper limit of reference values. HLA DQ2
and/or DQ8 were found in 97.6% of examined children. CONCLUSIONS: Tests based on
anti-TG IgA are more accurate for detecting CD in children with type 1 diabetes
than anti-DGP IgA. A high percentage of diabetic children carry HLA alleles
predisposing to CD, which indicates that genetic screening in this group of
patients is not obligated.
PMID- 29350068
TI - Primary Liver Cancers-Part 1: Histopathology, Differential Diagnoses, and Risk
Stratification.
AB - Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the 2 most common
primary malignant liver tumors, with hepatocellular and bile ductular
differentiation, respectively. This article reviews the key histopathological
findings of these 2 primary liver cancers and includes a review of the role of
ancillary testing for differential diagnosis, risk stratification according to
the American Joint Committee on Cancer (AJCC) staging recommendation, and a
review of precancerous lesions. A literature review was conducted to identify
articles with information relevant to precancerous precursors, current
histopathological classification, ancillary testing, and risk stratification of
primary malignant liver tumors. The histomorphology of normal liver, preinvasive
precursors, primary malignancies, and morphological variants, and the utilization
of ancillary tests for the pathological diagnosis are described. Dysplastic
nodules are the preinvasive precursors of HCC, and intraductal papillary
neoplasms of bile ducts and biliary intraepithelial neoplasia are the preinvasive
precursors of CC. Benign liver nodules including focal nodular hyperplasia and
adenomas are included in this review, since some forms of adenomas progress to
HCC and often they have to be differentiated from well-differentiated HCC. A
number of morphological variants of HCC have been described in the literature,
and it is necessary to be aware of them in order to render the correct diagnosis.
Risk stratification is still dependent on the AJCC staging system. The diagnosis
of primary liver carcinomas is usually straightforward. Application of the
appropriate ancillary studies aids in the differential diagnosis of difficult
cases. The understanding of the carcinogenesis of these malignancies has improved
with the standardization of the pathological classification of preinvasive
precursors and studies of the molecular pathogenesis. Risk stratification still
depends on pathological staging.
PMID- 29350071
TI - Disclosing respiratory co-infections: a broad-range panel assay for avian
respiratory pathogens on a nanofluidic PCR platform.
AB - Respiratory syndromes (RS) are among the most significant pathological conditions
in edible birds and are caused by complex coactions of pathogens and
environmental factors. In poultry, low pathogenic avian influenza A viruses,
metapneumoviruses, infectious bronchitis virus, infectious laryngotracheitis
virus, Mycoplasma spp. Escherichia coli and/or Ornithobacterium rhinotracheale in
turkeys are considered as key co-infectious agents of RS. Aspergillus sp.,
Pasteurella multocida, Avibacterium paragallinarum or Chlamydia psittaci may also
be involved in respiratory outbreaks. An innovative quantitative PCR method,
based on a nanofluidic technology, has the ability to screen up to 96 samples
with 96 pathogen-specific PCR primers, at the same time, in one run of real-time
quantitative PCR. This platform was used for the screening of avian respiratory
pathogens: 15 respiratory agents, including viruses, bacteria and fungi
potentially associated with respiratory infections of poultry, were targeted.
Primers were designed and validated for SYBR green real-time quantitative PCR and
subsequently validated on the Biomark high throughput PCR nanofluidic platform
(Fluidigm(c), San Francisco, CA, USA). As a clinical assessment, tracheal swabs
were sampled from turkeys showing RS and submitted to this panel assay. Beside
systematic detection of E. coli, avian metapneumovirus, Mycoplasma gallisepticum
and Mycoplasma synoviae were frequently detected, with distinctive co-infection
patterns between French and Moroccan flocks. This proof-of-concept study
illustrates the potential of such panel assays for unveiling respiratory co
infection profiles in poultry.
PMID- 29350072
TI - A new polyoxygenated abietane diterpenoid from the rattans of Bauhinia championii
(Benth.) Benth.
AB - A new polyoxygenated abietane diterpenoid, bauchampine A (1), together with seven
known compounds (2-8), were isolated from the rattans of Bauhinia championii
(Benth.) Benth. The structure of 1 was elucidated by extensive spectroscopic
methods and the known compounds were identified by comparison with the data
reported in the literature. New compound 1 was evaluated for its anti-rheumatoid
arthritis activity via examining its anti-proliferative effect on synoviocytes in
vitro. Compound 1 exhibited inhibitory effect on the proliferation of
synoviocytes with IC50 value comparable to that of methotrexate.
PMID- 29350073
TI - In their own words: a synthesis of the qualitative research on the experiences of
adults seeking asylum. A systematic review of qualitative findings in forced
migration.
AB - Quantitative research indicates that some forced migrants have mental health
needs. Asylum seekers are a group of forced migrants applying for asylum status
in a host country, and are often subject to rights restrictions and threat of
deportation, though little is known about subjective experiences of the asylum
journey and process of claiming asylum. The current paper therefore describes a
systematic review of the qualitative literature, examining asylum seekers
experiences of asylum journey, from country of origin, to arrival and adaptation
to host countries. A search of four databases yielded 122 studies.
Inclusion/exclusion criteria were applied and 15 studies were retained and
critically appraised. The country where research was conducted, study aims,
sample characteristics and methodological approaches were all critically reviewed
for included studies. Study aims fell into four themes; 'an aspect of the asylum
seeker journey'; 'psychological distress and wellbeing'; 'cultural identity and
adaptation to new environment' and 'social welfare, employment and housing'.
Studies were generally high quality and indicate issues around choice of asylum
destination, distress created by uncertainty around asylum decision and hostile
reactions of host communities. However, few studies have examined the experiences
of asylum seekers specifically, which is important given the unique circumstances
of this population.
PMID- 29350074
TI - Serum concentration and clinical significance of brain-derived neurotrophic
factor in patients with Parkinson's disease or essential tremor.
AB - Objectives The serum concentration of brain-derived neurotrophic factor (BDNF)
was compared among patients with Parkinson's disease (PD), patients with
essential tremor (ET), and healthy participants, and its association with
clinical features of PD and ET was assessed. Methods Demographic and clinical
data were collected from 60 patients with PD at different clinical stages, 60
patients with ET, and 60 controls. All participants' serum BDNF concentrations
were measured. Their motor abilities and activity were assessed by the Unified PD
Rating Scale and the Hoehn and Yahr (H-Y) staging scale. Results Serum BDNF was
significantly lower in patients with PD than in patients with ET and controls.
BDNF decreased only in the early disease stages (H-Y stages I and II), but
increased markedly in the advanced stages (H-Y stages III-V). There was no
significant difference between patients with ET and controls. The BDNF
concentration was negatively correlated with age at PD onset and positively
associated with disease duration, severity of PD symptoms, and treatment with L
DOPA. Conclusions A low serum BDNF concentration may serve as a biomarker in the
early stages of PD, whereas a high concentration with PD progression may be due
to treatment with L-DOPA in the advanced stages.
PMID- 29350075
TI - Characterization of the proteome and lipidome profiles of human lung cells after
low dose and chronic exposure to multiwalled carbon nanotubes.
AB - The effects of long-term chronic exposure of human lung cells to multi-walled
carbon nanotubes (MWCNT) and their impact upon cellular proteins and lipids were
investigated. Since the lung is the major target organ, an in vitro normal
bronchial epithelial cell line model was used. Additionally, to better mimic
exposure to manufactured nanomaterials at occupational settings, cells were
continuously exposed to two non-toxic and low doses of a MWCNT for 13-weeks.
MWCNT-treatment increased ROS levels in cells without increasing oxidative DNA
damage and resulted in differential expression of multiple anti- and pro
apoptotic proteins. The proteomic analysis of the MWCNT-exposed cells showed that
among more than 5000 identified proteins; more than 200 were differentially
expressed in the treated cells. Functional analyses revealed association of these
differentially regulated proteins to cellular processes such as cell death and
survival, cellular assembly, and organization. Similarly, shotgun lipidomic
profiling revealed accumulation of multiple lipid classes. Our results indicate
that long-term MWCNT-exposure of human normal lung cells at occupationally
relevant low-doses may alter both the proteome and the lipidome profiles of the
target epithelial cells in the lung.
PMID- 29350076
TI - Health Care Public Sector Share and the U.S. Life Expectancy Lag: A Country-level
Longitudinal Study.
AB - Growing research on the political economy of health has begun to emphasize
sociopolitical influences on cross-national differences in population health
above and beyond economic growth. While this research investigates the impact of
overall public health spending as a share of GDP ("health care effort"), it has
for the most part overlooked the distribution of health care spending across the
public and private spheres ("public sector share"). I evaluate the relative
contributions of health care effort, public sector share, and GDP to the large
and growing disadvantage in U.S. life expectancy at birth relative to peer
nations. I do so using fixed effects models with data from 16 wealthy democratic
nations between 1960 and 2010. Results indicate that public sector share has a
beneficial effect on longevity net of the effect of health care effort and that
this effect is nonlinear, decreasing in magnitude as levels rise. Moreover,
public sector share is a more powerful predictor of life expectancy at birth than
GDP per capita. This study contributes to discussions around the political
economy of health, the growth consensus, and the American lag in life expectancy.
Policy implications vis-a-vis the U.S. Affordable Care Act are discussed.
PMID- 29350077
TI - In hospital with a hearing impaired child - How parents experience communication
between nurses and their child
AB - Background: In daily communication, children with hearing impairment are
restricted and dependent on their parents' help. In case of a hospitalisation,
the risk of insufficient information and resulting traumatisation for those
children is high. The aim of this study is the investigation of the communicative
needs of the children concerned in order to avoid negative consequences of a
hospitalisation and of inappropriate communication by nursing staff. Aim: This
study explores how parents of a child with hearing impairment experience the
communication between the nursing staff and their hospitalised child. Method: The
study was conducted together with an advisory centre for hearing-impaired
children, where most of the parents could be recruited. Narrative, semi
structured interviews were conducted. The transcribed interviews were analysed
according to the method of interpretative phenomenology. Results: The parents
expressed their wish for affectionate verbal and nonverbal love and care for
their child. They often experienced the nursing staff having little time, that
there was no continuity and that the communicative needs of the child were not
recognised. Since the parents did not think the nursing staff were capable of
communicating with the child and because they wanted to protect him or her, they
adopted a mediating role. Conclusions: Besides the sensitisation of the nursing
staff, time resources, continuity, professional knowledge and benevolence in the
nursing care of a child with hearing impairment play a fundamental role.
PMID- 29350078
TI - External Control of Knowledge of Results: Learner Involvement Enhances Motor
Skill Transfer.
AB - Providing the learner control over aspects of practice has improved the process
of motor skill acquisition, and self-controlled knowledge of results (KR)
schedules have shown specific advantages over externally controlled ones. A
possible explanation is that self-controlled KR schedules lead learners to more
active task involvement, permitting deeper information processing. This study
tested this explanatory hypothesis. Thirty undergraduate volunteers of both
sexes, aged 18 to 35, all novices in the task, practiced transporting a tennis
ball in a specified sequence within a time goal. We compared a high-involvement
group (involvement yoked, IY), notified in advance about upcoming KR trials, to
self-controlled KR (SC) and yoked KR (YK) groups. The experiment consisted of
three phases: acquisition, retention, and transfer. We found both IY and SC
groups to be superior to YK for transfer of learning. Postexperiment participant
questionnaires confirmed a preference for receiving KR after learner-perceived
good trials, even though performance on those trials did not differ from
performance on trials without KR. Equivalent IY and SC performances provide
support for the benefits of task involvement and deeper information processing
when KR is self-controlled in motor skill acquisition.
PMID- 29350079
TI - Differences in home blood pressure and pulse rates between singleton and twin
pregnancies.
AB - Objectives To evaluate home blood pressure (HBP) measurements during pregnancy
and postpartum and investigate differences between singleton and twin
pregnancies. Methods This prospective study involved normotensive, pregnant women
who were planning to give birth at Saitama Medical Centre, Saitama, Japan between
September 2013 and March 2017. HBP and pulse rate were measured twice daily and
clinical blood pressure values were determined from patient records. Results HBP
values were available from 101 participants; 69 women with singleton and 32 women
with twin pregnancies. Systolic BP was statistically significantly higher in twin
pregnancies from 23 weeks of gestation until 8 weeks after delivery compared with
singleton pregnancies. Pulse rate was also statistically significantly higher
between 11 and 30 weeks gestation in women with twin pregnancies compared with
those with singleton pregnancies. Conclusions BP monitoring is important in the
management of twin pregnancies, especially during the later gestational weeks and
postpartum period and HBP would facilitate this monitoring.
PMID- 29350080
TI - IRF2BP2-RARA t(1;17)(q42.3;q21.2) APL blasts differentiate in response to all
trans retinoic acid.
PMID- 29350081
TI - Assessment of the anterolateral ligament of the knee by 1.5 T magnetic resonance
imaging.
AB - Objective This study was performed to evaluate the visibility of the knee's
anterolateral ligament (ALL) by magnetic resonance (MR) imaging when evaluating
injuries of the ALL in relation to injuries of the anterior cruciate ligament
(ACL). Methods Two reviewers retrospectively analyzed MR images for the
visibility and dimensions of the ALL and the relationship between ALL and ACL
injuries. The intraclass correlation coefficient (ICC) and kappa analysis were
used to assess interobserver reliability. The chi-square test was used to assess
the relationship between ALL and ACL injuries. Results The entire ALL was viewed
on 82% of all MR images. The ICC for ALL visualization ranged from moderate to
perfect between the two readers. There was almost perfect agreement between the
reviewers when evaluating ALL dimensions. The mean length +/- standard error,
median thickness, and mean width +/- standard error of the ALL were 36.5 +/- 0.6
mm, 2.5 mm, and 8.2 +/- 0.2 mm, respectively. A statistically significant
relationship was observed between ALL and ACL injuries. Conclusion The ALL was
visible on most MR images, allowing ALL injuries to be noted during routine MR
image interpretation. Radiologists should note concomitant ACL and ALL injuries
as part of their assessments.
PMID- 29350083
TI - From "a Fair Game" to "a Form of Covert Research": Research Ethics Committee
Members' Differing Notions of Consent and Potential Risk to Participants Within
Social Media Research.
AB - Social media (SM) research presents new challenges for research ethics committees
(RECs) who must balance familiar ethical principles with new notions of public
availability. This article qualitatively examines how U.K. REC members view this
balance in terms of risk and consent. While it found significant variance
overall, there were discernible experience-based trends. REC members with less
experience of reviewing SM held inflexible notions of consent and risk that could
be categorized as either relying on traditional notions of requiring direct
consent, or viewing publicly available data as "fair game." More experienced REC
members took a more nuanced approach to data use and consent. We conclude that
the more nuanced approach should be best practice during ethical review of SM
research.
PMID- 29350082
TI - Quantitative DTI metrics in a canine model of Krabbe disease: comparisons versus
age-matched controls across multiple ages.
AB - Purpose The purpose of this study was to compare quantitative diffusion tensor
imaging metrics in dogs affected with a model of Krabbe disease to age-matched
normal controls. We hypothesized that fractional anisotropy would be decreased
and radial diffusivity would be increased in the Krabbe dogs. Methods We used a
highly reproducible region-of-interest interrogation technique to measure
fractional anisotropy and radial diffusivity in three different white matter
regions within the internal capsule and centrum semiovale in four Krabbe affected
brains and three age-matched normal control brains. Results Despite all four
Krabbe dogs manifesting pelvic limb paralysis at the time of death, age-dependent
differences in DTI metrics were observed. In the 9, 12, and 14 week old Krabbe
dogs, FA values unexpectedly increased and RD values decreased. FA values were
generally higher and RD values generally lower in both regions of the internal
capsule in the Krabbe brains during this period. FA values in the brain from the
16 week old Krabbe dog decreased and were lower than in control brains and RD
values increased and were higher than in control brain. Conclusion Our findings
suggest that FA and RD in the internal capsule and centrum semiovale are affected
differently at different ages, despite disease having progressed to pelvic limb
paralysis in all dogs evaluated. In 9, 12, and 14 week old Krabbe dogs, higher FA
values and lower RD values are seen in the internal capsule. However, in the 16
week old Krabbe dog, lower FA and higher RD values are seen, consistent with
previous observations in Krabbe dogs, as well as observations in human Krabbe
patients.
PMID- 29350084
TI - Exploring assistive technology use to support cognition in college students with
histories of mild traumatic brain injury.
AB - PURPOSE: College students with mild traumatic brain injury (mTBI) may experience
chronic cognitive deficits necessitating use of external supports for daily task
completion. The purpose of this study was to explore cognitive support system
selection and use by students with histories of mTBI when completing novel
prospective memory tasks. MATERIALS AND METHODS: We implemented a multiple case
study, sequential explanatory mixed-methods design with three participants.
Participants completed four experimental phases: (1) background history
collection, cognitive assessment completion, pre-trial interview, and selection
of two external supports for trial phase use; (2) trial Phase 1 (i.e., 10-days);
(3) trial Phase 2 (i.e., 10 days); and (4) post-trial exit interview. We examined
participants' support type and characteristic preferences and evaluated task
execution accuracy when implementing differing supports. RESULTS: Participants
expressed both collective and unique cognitive aid preferences before trial
completion. Trial phase results revealed that task completion accuracy did not
alter substantially between trials; however, personal preferences and perceived
usefulness of trialled cognitive aid systems appeared to impact support
implementation and effectiveness. Themes emerged from post-trial interview
relating to the (a) necessity for differing functions of individual systems and
(b) importance of trialling devices prior to selection. CONCLUSIONS: Results
emphasize the necessity of person-centred approaches to treatment due to the
variability of performance accuracy and system preferences. The cognitive aid
selection and implementation intervention protocol piloted in this study appears
beneficial for understanding unique strengths and challenges for college students
following mTBI and may be useful for clinicians working with individuals with
mTBI. Implications for rehabilitation College-aged students with mild traumatic
brain injury report unique preferences for no- and high-tech cognitive aids;
however, similar patterns emerge relating to preferred system characteristics.
Facilitating several trial periods prior to selection and implementation of
external cognitive supports for individuals with mild traumatic brain injury is
essential given the preference changes that occur post-trial. Implementing a
three-phase external cognitive aid selection process appears beneficial for young
adults with mild brain injuries.
PMID- 29350085
TI - Divergent Classification Methods of Post-Concussion Syndrome after Mild Traumatic
Brain Injury: Prevalence Rates, Risk Factors, and Functional Outcome.
AB - Mild traumatic brain injury (mTBI) is a common diagnosis and approximately one
third of mTBI patients experience a variety of cognitive, emotional,
psychosocial, and behavioral post-concussion symptoms. When a cluster of these
symptoms persists for more than 3 months they are often classified as post
concussion syndrome (PCS). The objective of this study was to determine
prevalence rates, risk factors, and functional outcome associated with PCS 6
months after mTBI, applying divergent classification methods. Follow-up
questionnaires at 6 months after mTBI included the Rivermead Post-Concussion
Symptoms Questionnaire (RPQ) and the Glasgow Outcome Scale Extended (GOSE). The
RPQ was analyzed according to different classification methods: the mapped
International Classification of Diseases, 10th revision (ICD-10)/Diagnostic and
Statistical Manual of Mental Disorders, 4th edition (DSM-IV), the RPQ total
score, the RPQ3 and the three-factor model using two different cutoff points
(mild or worse and moderate or worse). Our results from a sample of 731 mTBI
patients showed that prevalence rates of PCS ranged from 11.4% to 38.7% using
divergent classification methods. According to all eight methods, 6.3% (n = 46)
of mTBI patients experienced PCS. Applying the divergent classification methods
resulted in a different set of predictors being statistically significantly
associated with PCS, and a different percentage of overlap with functional
impairment, measured with the GOSE. In conclusion, depending on the
classification method and rating score used, prevalence rates of PCS deviated
considerably. For future research, consensus regarding the diagnostic criteria
for PCS and the analysis of the RPQ should be reached, to enhance comparability
of studies regarding PCS after mTBI.
PMID- 29350086
TI - Hematoma clearance as a therapeutic target in intracerebral hemorrhage: From
macro to micro.
AB - Despite the absence of an intervention shown to improve outcomes in intracerebral
hemorrhage, preclinical work has led to a greater understanding of the pathologic
pathways of brain injury. Methods targeting hematoma clearance through both
macroscopic (surgical) and microscopic (endogenous phagocytosis) means are
currently under investigation, with multiple clinical trials ongoing. Macroscopic
methods for removal involve both catheter- and endoscope-based therapies to
remove the hematoma through minimally invasive surgery. Microscopic methods
targeting hematoma clearance involve augmenting endogenous clearance pathways for
red blood cells and altering the balance between phagocytosis and red blood cell
lysis with the release of potentially harmful constituents (e.g. hemoglobin and
iron) into the extracellular space.
PMID- 29350087
TI - Segmentation of tongue shapes during vowel production in magnetic resonance
images based on statistical modelling.
AB - Quantification of the anatomic and functional aspects of the tongue is pertinent
to analyse the mechanisms involved in speech production. Speech requires dynamic
and complex articulation of the vocal tract organs, and the tongue is one of the
main articulators during speech production. Magnetic resonance imaging has been
widely used in speech-related studies. Moreover, the segmentation of such images
of speech organs is required to extract reliable statistical data. However,
standard solutions to analyse a large set of articulatory images have not yet
been established. Therefore, this article presents an approach to segment the
tongue in two-dimensional magnetic resonance images and statistically model the
segmented tongue shapes. The proposed approach assesses the articulator
morphology based on an active shape model, which captures the shape variability
of the tongue during speech production. To validate this new approach, a dataset
of mid-sagittal magnetic resonance images acquired from four subjects was used,
and key aspects of the shape of the tongue during the vocal production of
relevant European Portuguese vowels were evaluated.
PMID- 29350088
TI - The use of synthetic ligaments in the design of an enhanced stability total knee
joint replacement.
AB - Current total knee replacement designs work to address clinically desired knee
stability and range of motion through a balance of retained anatomy and added
implant geometry. However, simplified implant geometries such as bearing
surfaces, posts, and cams are often used to replace complex ligamentous
constraints that are sacrificed during most total knee replacement procedures.
This article evaluates a novel total knee replacement design that incorporates
synthetic ligaments to enhance the stability of the total knee replacement
system. It was hypothesized that by incorporating artificial cruciate ligaments
into a total knee replacement design at specific locations and lengths, the
stability of the total knee replacement could be significantly altered while
maintaining active ranges of motion. The ligament attachment mechanisms used in
the design were evaluated using a tensile test, and determined to have a safety
factor of three with respect to expected ligamentous loading in vivo. Following
initial computational modeling of possible ligament orientations, a physical
prototype was constructed to verify the function of the design by performing
anterior/posterior drawer tests under physiologic load. Synthetic ligament
configurations were found to increase total knee replacement stability up to 94%
compared to the no-ligament case, while maintaining total knee replacement
flexion range of motion between 0 degrees and 120 degrees , indicating that a
total knee replacement that incorporates synthetic ligaments with calibrated
location and lengths should be able to significantly enhance and control the
kinematic performance of a total knee replacement system.
PMID- 29350089
TI - A comparative analysis of internal bone remodelling concepts in a novel implant
for direct skeletal attachment of limb prosthesis evaluation: A finite element
analysis.
AB - Nowadays, numerous internal bone remodelling concepts are under development, in
order to estimate long-term functionality of implants by evaluating the intensity
of stress-shielding effect. This effect is also analysed for the implants for
direct skeletal attachment, considered as a better exoprosthesis fixation method
than prosthetic sockets. Most of bone remodelling approaches are based on basic
concepts, differing with certain assumptions, which may affect the accuracy of
the results. This article compares commonly used internal bone remodelling
concepts and evaluates the functionality of the proposed Limb Prosthesis
Osseointegrated Fixation System for direct skeletal attachment of limb prosthesis
in comparison with two currently available implants: the Intraosseous
Transcutaneous Amputation Prosthesis and the Osseointegrated Prostheses for the
Rehabilitation of Amputees. Three concepts were chosen: without and with lazy
zone and with the use of quadratic formula which considers bone overloading.
Therefore, three finite element models were created with identical femur
implanted with each of analysed implants. The implants were loaded with loads
that refer to two stages of gait cycle (heel strike and toe-off). The analysed
concepts have given similar results, allowing to assume that each of them can be
successfully used to estimate internal bone remodelling around analysed implants
for direct skeletal attachment of limb prosthesis. The results also present
higher functionality of the proposed implant for direct skeletal attachment of
limb prosthesis due to a significant reduction in stress-shielding in the
analysed areas around implant in comparison with the Intraosseous Transcutaneous
Amputation Prosthesis and the Osseointegrated Prostheses for the Rehabilitation
of Amputees. It suggests that the proposed design is a better alternative to the
currently used solutions.
PMID- 29350090
TI - Demographic determinants and outcome of in vitro fertilization (IVF) services in
Saudi Arabia.
AB - Objectives To assess the demographic characteristics and outcomes of couples
undergoing in vitro fertilisation (IVF) treatment at a private hospital in Al
Qassim district, Saudi Arabia. Methods For this retrospective study, information
was extracted from the hospital electronic database and IVF unit medical records.
Results 2259 couples underwent 2703 IVF/ICSI cycles during 2014 to 2016. The
utilization rate was approximately 1000 cycle per million of inhabitants. Mean
ages +/- standard deviation (SD) for women and men were 32.9 +/- 5.7 and 39.2 +/-
7.4 years, respectively. More couples were diagnosed with secondary infertility
(55.2%) than primary infertility (44.8%). Male factor was the commonest single
indication for IVF (36.2%). Mean +/- SD infertility duration was 4.70 +/- 4.03
years. Overall, 949 couples had a successful pregnancy. Age-specific pregnancy
rates (PR) were highest for women <35 years (39.8%) and lowest for women >40
years (11.6%). Male age and infertility duration had no effect on PR but sperm
source (fresh vs. frozen) and female age had significant impacts. However, fresh
sperm was used in 90.6% cycles whereas frozen sperm was used in 9.4% cycles.
Conclusions IVF treatment outcomes in the Al Qassim district are within the
boundaries of average international success rates. Infertile couples seeking IVF
services should be counselled with regard to important prognostic factors.
PMID- 29350091
TI - Stent-assisted coiling of cerebral aneurysms with the Neuroform Atlas stent.
AB - Objectives The Neuroform Atlas stent (AS) is the smallest intracranial stent with
an open-cell design. This study reports the first clinical experience with AS.
Methods All intracranial aneurysms treated by stent-assisted coiling using a
single AS in a single institution were retrospectively evaluated. Patient
demographics, aneurysm characteristics, angles between the parent artery and
stented branch, technical success, and clinical and angiographic follow-up were
analyzed. Results Fifty-five consecutive aneurysms treated with AS-assisted
coiling were included. Of these, 69.1% were located distal to the circle of
Willis. Technical success rate was 100%. The mean diameters of proximal and
distal parent arteries were 2.62 mm (range 1.5-4.4) and 1.8 mm (range 0.8-3.5),
respectively. Except for a minor stroke in a patient who completely discontinued
antiplatelet therapy on postoperative day 4, there were no clinical events with
permanent sequelae, and 94.1% of patients had Raymond-Roy score of 1 or 2
aneurysmal occlusion at a mean follow-up duration of 7.9 months. Although the
angle between the parent artery and the stented branch increased significantly (
p < 0.001) with time, the angular change at follow-up was only 16.45 +/- 11.03
degrees and was inversely correlated both with preoperative angle and the
diameter of the distal parent artery ( r = -0.465 and r = -0.433, respectively, p
= 0.004 for both). Conclusion AS-assisted coiling was associated with a favorable
early clinical outcome and angiographic results in this series. This stent can be
used for distally located aneurysms and results in minimal alteration of the
arterial anatomy.
PMID- 29350092
TI - Focus on the target: Angiographic features of the fistulous point and prognosis
of transvenous embolization of cavernous sinus dural arteriovenous fistula.
AB - Background and purpose Transvenous embolization (TVE) is widely utilized as an
effective and safe treatment option for cavernous sinus dural arteriovenous
fistula (CS-dAVF); however, detecting the exact location of the fistula is
challenging. The present study identified the angiographic features of the
fistulous point and evaluated the match with the microcatheter tip and fistulous
point. Materials and methods An analysis cohort of 45 consecutive patients with
CS-dAVF treated by TVE was analyzed retrospectively. The patients were divided
into two groups, 22 matches and 23 mismatches, according to whether the fistulous
point and the microcatheter tip were in the same compartment of the cavernous
sinus (CS). The angiographic findings, the location of the fistulas, the position
of the microcatheter tips, the volume of embolic materials, complications, and
outcomes were assessed. Results Several angiographic features defined the
fistulous points, such as the early opacified area, jellyfish-like sign, changes
in the density of the contrast medium, the juncture of different arterial supply,
enlarged feeders, and hand-injection angiograms. The fistulas were primarily in
the posterosuperior portion of the CS (80%) and medial side (73.3%) according to
the internal carotid artery. Both groups achieved effective TVE; the matched
group required less embolic material than the mismatched group ( p = 0.024). The
patients with cranial nerve dysfunction (CND) required more embolic materials
than others ( p = 0.032). Conclusion The fistulous point in most of the CS-dAVFs
could be isolated by careful analysis of the angiography images. The matching of
the microcatheter tip and fistulous point in the same compartment of CS can
reduce the dosage of embolic materials, and a low volume of embolic materials
might cause fewer CND complications.
PMID- 29350093
TI - Thiobarbituric acid-reactive substances relate to arterial stiffness and blood
pressure in 6 to 8-year-old boys stratified by maternal risk.
AB - Early cardiovascular disease (CVD) onset can be inflicted by familial
cardiovascular and lifestyle risk factors. We aimed to compare phenotypic
characteristics and explore associations between oxidative stress and vascular
function in boys stratified by maternal cardiovascular and lifestyle risk. We
included 40 Black and 41 White boys (ages 6-8 years), along with the biological
mother of each child. The study population was divided into two groups
(nonmaternal risk vs. maternal risk) according to maternal risk predetermined by
their selfreported cardiovascular and lifestyle risk factors. Pulse wave velocity
(PWV) was measured at various sites and blood pressures were recorded. Urine
samples were collected for analyses of thiobarbituric acid-reactive substances
(TBARS), 8-hydroxy-2-deoxy guanosine (8-OHdG), albumin, and creatinine. Higher
levels of urinary albumin to creatinine ratio (uACR) were found in the maternal
risk group compared to the nonmaternal risk group (p = .038). Multiple regression
analysis in the maternal risk group revealed diastolic blood pressure (R2 =
0.159; beta = 0.293; p = .050), carotid femoral PWV (R2 = 0.158; beta = 0.297; p
= .038) and carotid dorsalis pedis PWV (adj R2 = 0.322; beta = 0.505; p < .001)
to be positively associated with TBARS, while an inverse association of uACR (R2
= 0.161; beta = -0.261; p = .046) with TBARS was observed. Also, in the maternal
risk group, independent associations of DBP (R2 = 0.273; beta = 0.289; p = .040)
and uACR (R2 = 0.283; beta = 0.268; p = .027) with 8-OHdG were indicated. In
boys, as young as 6 years of age, oxidative stress related to arterial stiffness
and diastolic blood pressure was observed. This association was only evident in
boys with linked maternal lifestyle and cardiovascular risk factors, suggesting
potential family-related early onset of cardiovascular risk.
PMID- 29350095
TI - The Bandwidth of Diagnostic Horizontal Structure for Face Identification.
AB - Horizontally oriented spatial frequency components are a diagnostic source of
face identity information, and sensitivity to this information predicts upright
identification accuracy and the magnitude of the face-inversion effect. However,
the bandwidth at which this information is conveyed, and the extent to which
human tuning matches this distribution of information, has yet to be
characterized. We designed a 10-alternative forced choice face identification
task in which upright or inverted faces were filtered to retain horizontal or
vertical structure. We systematically varied the bandwidth of these filters in 10
degrees steps and replaced the orientation components that were removed from the
target face with components from the average of all possible faces. This
manipulation created patterns that looked like faces but contained diagnostic
information in orientation bands unknown to the observer on any given trial.
Further, we quantified human performance relative to the actual information
content of our face stimuli using an ideal observer with perfect knowledge of the
diagnostic band. We found that the most diagnostic information for face
identification is conveyed by a narrow band of orientations along the horizontal
meridian, whereas human observers use information from a wide range of
orientations.
PMID- 29350094
TI - Medium-chain acyl-CoA dehydrogenase deficiency: Two novel ACADM mutations
identified in a retrospective screening.
AB - Objective The aim of this study was to determine whether an expanded newborn
screening programme, which is not yet available in Slovenia, would have detected
the first two patients with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency
in the country. Two novel ACADM mutations are also described. Methods Both
patients were diagnosed clinically; follow-up involved analysis of organic acids
in urine, acylcarnitines in dried blood spots, and genetic analysis of ACADM. Cut
off values of acylcarnitines in newborns were established using analysis of
10,000 newborns in a pilot screening study. Results In both patients, analysis of
the organic acids in urine showed a possible beta-oxidation defect, while the
specific elevation of acylcarnitines confirmed MCAD deficiency. Subsequent
genetic analysis confirmed the diagnosis; both patients were compound
heterozygotes, each with one novel mutation (c.861 + 2T > C and c.527_533del).
The results from a retrospective analysis of newborn screening cards clearly
showed major elevations of MCAD-specific acylcarnitines in the patients.
Conclusions An expanded newborn screening programme would be beneficial because
it would have detected MCAD deficiency in both patients before the development of
clinical signs. Our study also provides one of the first descriptions of ACADM
mutations in Southeast Europe.
PMID- 29350096
TI - alpha-Tocopherol protected against cobalt nanoparticles and cocl2 induced
cytotoxicity and inflammation in Balb/3T3 cells.
AB - CONTEXT: Currently, tissue damage induced by cobalt nanoparticles (CoNPs) and
cobalt ions (Co2+) are the most serious adverse effect in the patients with metal
on-metal hip prostheses. Therefore, an urgent need exists for the identification
of the mechanisms and the development of therapeutic strategies to limit it.
OBJECTIVE: We aimed to explore the mechanisms of cytotoxicity of CoNPs and Co2+
and developed strategies to reduce this cytotoxicity with alpha-tocopherol
treatment. METHODS: To evaluate the protective effect of alpha-tocopherol,
Balb/3T3 cells were pretreated with 10 MUM alpha-tocopherol for 24 h. The cells
were then exposed to different concentrations of CoNPs and Co2+ for 12 h, 24 h
and 48 h. The cell viabilities, reactive oxygen species (ROS), inflammatory
cytokines and MAP kinase (MAPK) levels were measured. RESULTS: CoNPs and Co2+ can
induce the increase of ROS and inflammatory cytokines in Balb/3T3 cells, such as
tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta) and
interleukin-6 (IL-6). However, alpha-tocopherol pretreatment can significantly
prevent cytotoxicity induced by CoNPs and Co2+, decrease ROS production and
decrease levels of inflammatory cytokines in Balb/3T3 cells. Additionally, MAPK
pathway may be involved in the protection of alpha-tocopherol against
cytotoxicity induced by CoNPs and Co2+ in vitro. CONCLUSIONS: Our results provide
new insights into the potential therapeutic use of alpha-tocopherol in the
prevention and treatment of various oxidative- or inflammatory stress-related
inflammation and injuries.
PMID- 29350097
TI - Paternal Perinatal Depression Assessed by the Edinburgh Postnatal Depression
Scale and the Gotland Male Depression Scale: Prevalence and Possible Risk
Factors.
AB - Several studies have used the Edinburgh Postnatal Depression Scale (EPDS),
developed to screen new mothers, also for new fathers. This study aimed to
further contribute to this knowledge by comparing assessment of possible
depression in fathers and associated demographic factors by the EPDS and the
Gotland Male Depression Scale (GMDS), developed for "male" depression screening.
The study compared EPDS score >=10 and >=12, corresponding to minor and major
depression, respectively, in relation to GMDS score >=13. At 3-6 months after
child birth, a questionnaire was sent to 8,011 fathers of whom 3,656 (46%)
responded. The detection of possibly depressed fathers by EPDS was 8.1% at score
>=12, comparable to the 8.6% detected by the GMDS. At score >=10, the proportion
detected by EPDS increased to 13.3%. Associations with possible risk factors were
analyzed for fathers detected by one or both scales. A low income was associated
with depression in all groups. Fathers detected by EPDS alone were at higher risk
if they had three or more children, or lower education. Fathers detected by EPDS
alone at score >=10, or by both scales at EPDS score >=12, more often were born
in a foreign country. Seemingly, the EPDS and the GMDS are associated with
different demographic risk factors. The EPDS score appears critical since 5% of
possibly depressed fathers are excluded at EPDS cutoff 12. These results suggest
that neither scale alone is sufficient for depression screening in new fathers,
and that the decision of EPDS cutoff is crucial.
PMID- 29350098
TI - Commentary to 18F-GP1, a Novel PET Tracer Designed for High-Sensitivity, Low
Background Detection of Thrombi: Imaging Activated Platelets in Clots-Are We
Getting There?
AB - Thrombus formation can lead to heart attacks, stroke and pulmonary embolism,
which are major causes of mortality. Current standard diagnostic imaging methods
detect anatomic abnormalities such as vascular flow impairment but have
limitations. By using a targeted molecular imaging approach critical components
of a pathology can be selectively visualized and exploited for an improved
diagnosis and patient management. The GPIIb/IIIa receptor is abundantly and
specifically exposed on activated platelets and is the key receptor in thrombus
formation. This commentary describes the current status of GPIIb/IIIa-based PET
imaging approaches with a focus on the recently published preclinical data of the
small-molecule PET tracer 18F-GP1. Areas of future research and potential
clinical applications are discussed that may lead to an improved detection of
critical thromboembolic events and an optimization of available antithrombotic
therapies by tracking activated platelets.
PMID- 29350099
TI - Does shortening the pitch make junior cricketers bowl better?
AB - In order to get bounce and movement seam bowlers need to bowl the ball "into" the
pitch. Standard deliveries by elite players are typically projected at around 7
degrees below horizontal. In contrast, young players currently often need to
release the ball almost horizontally in an effort to get the ball to bounce close
enough to the batter. We anticipated that shortening the pitch could be a simple
way to help young bowlers to release the ball at a better angle and with more
consistency. Twenty county or best in club age group under 10 and under 11 seam
bowlers were analysed bowling indoors on two different pitch lengths. They were
found to project the ball on average 3.4 degrees further below horizontal on a
16 yard pitch compared with a 19 yard pitch, while ball speed and position at
release changed negligibly. Pitch length did not affect the consistency of the
release parameters. The shorter pitch led to a ball release angle closer to that
of elite bowlers without changing release speed, and this should enable players
to achieve greater success and develop more variety in their bowling.
PMID- 29350100
TI - Transorbital Doppler with carotid siphon monitoring detects right-to-left shunt
effectively.
AB - Background Transtemporal Doppler (TTD) with middle cerebral artery (MCA) is
widely used for right-to-left shunt (RLS) detection. However, an alternative
method for patients without suitable temporal bone windows should be established.
The present study prospectively evaluated the effectiveness of transorbital
Doppler (TOD) with carotid siphon (CS) monitoring in detecting RLS. Methods A
total of 357 subjects with sufficient temporal bone windows underwent
simultaneous TTD with MCA and TOD with CS. After injection of microbubbles, the
numbers of artificial high-intensity signals were recorded at rest and after
Valsalva maneuver. Results TOD with CS detected RLS in 146 patients. Sensitivity
was 97.1%, specificity 95%, positive predictive value 92.5%, and negative
predictive value 98.1%. The total positive rates for RLS detection by CS (40.9%)
and MCA (37.8%) monitoring were comparable without significant difference, but
TOD with CS detected significantly more grade 2 and 3 RLS than TTD with MCA (p =
0.001). The RLS rates of cryptogenic stroke patients was significantly higher
than that of healthy controls, and RLS in cryptogenic stroke was remarkably
higher than that in transient ischemia attack patients (p < 0.05). TOD with CS
examined significantly more grade 2 and 3 RLSs than the MCA approach in the
cryptogenic stroke patients (p = 0.037). Conclusion TOD with CS monitoring is
able to detect RLS effectively in different populations including healthy
subjects, cryptogenic stroke, transient ischemia attack, and migraine patients.
In comparing to the TTD with MCA approach, TOD with CS monitoring could detect
comparable rate of RLS, but more high grades of RLS.
PMID- 29350101
TI - Biomimetic Composite Scaffold Containing Small Intestinal Submucosa and
Mesoporous Bioactive Glass Exhibits High Osteogenic and Angiogenic Capacity.
AB - Biomaterials with excellent osteogenic and angiogenic activities are desirable to
repair massive bone defects. Decellularized matrix from porcine small intestinal
submucosa (SIS) has attracted particular attention for tissue regeneration
because it has strong angiogenic effects and retains plentiful bioactive
components. However, it has inferior osteoinductivity and osteoconductivity. In
this study, we developed porous composite of SIS combined with mesoporous
bioactive glass (SIS/MBG) with the goal of improving the mechanical and
biological properties. SIS/MBG scaffolds showed uniform interconnected macropores
(~150 MUm), high porosity (~76%), and enhanced compressive strength (~0.87 MPa).
The proliferation and osteogenic gene expression (Runx2, ALP, Ocn, and Col
Ialpha) of rat bone marrow stromal cells (rBMSCs) as well as the proliferation,
angiogenic gene expression (VEGF, bFGF, and KDR), and tube formation capacity of
human umbilical vein endothelial cells (HUVECs) in SIS/MBG scaffolds were
significantly upregulated compared with nonmesoporous bioactive glass (BG)
modified SIS (SIS/BG) and SIS-only scaffolds. Western blot analysis revealed that
SIS/MBG induced rBMSCs to osteogenic differentiation through the activation of
Wnt/beta-Catenin signaling pathway, and SIS/MBG enhanced angiogenic activity of
HUVEC through the activation of PI3k/Akt pathways. The in vivo results
demonstrated that SIS/MBG scaffolds significantly enhanced new bone formation and
neovascularization simultaneously in critical-sized rat calvarial defects as
compared with SIS/BG and SIS. Collectively, the osteostimulative and
angiostimulative biomimetic composite scaffold SIS/MBG represents an exciting
biomaterial option for bone regeneration.
PMID- 29350102
TI - Preoperative Clinical and Sonographic Predictors for Lateral Cervical Lymph Node
Metastases in Sporadic Medullary Thyroid Carcinoma.
AB - BACKGROUND: Total thyroidectomy and cervical lymph node (LN) dissection is
generally recommended in patients with medullary thyroid carcinoma (MTC).
However, there is no clear evidence for whom to perform prophylactic lateral neck
dissection in MTC patients without evident lateral cervical lymph node (LCLN)
metastasis in preoperative images. This study evaluated the preoperative features
for predicting the LCLN metastasis of MTC. METHODS: The study included 26 MTC
patients with LCLN metastasis at initial surgery (N1b group) and 47 MTC patients
without any LN metastasis or recurrence of disease (N0-NED group). The
association between LCLN metastasis and preoperative clinical and sonographic
characteristics (size, location, solid component, shape, margin, echogenicity,
calcification, and subcapsular location of the tumor) were evaluated. RESULTS:
There were no significant differences in age and sex between the N1b and N0-NED
groups. Preoperative serum levels of calcitonin >65 pg/mL were associated with
LCLN metastasis (p < 0.001). In preoperative neck ultrasonography (US), patients
in the N1b group were more commonly found with a larger tumor (>1.5 cm) of
irregular shape with a spiculated margin and a subcapsular location than those in
the N0-NED group (p = 0.029, p < 0.001, p < 0.001, and p < 0.001, respectively).
Increases in the number of these LCLN metastasis-related features were
significantly associated with higher risk for LCLN metastasis (p < 0.001). The
presence of two or more predictors was an appropriate cutoff point for predicting
LCLN metastasis of MTC with 73.1% sensitivity and 91.5% specificity. CONCLUSIONS:
MTC tumors with high preoperative calcitonin levels (>65 pg/mL), larger size
(>1.5 cm), irregular shape, spiculated margins, and subcapsular locations in the
neck US are at higher risk for LCLN metastasis. MTC patents with fewer than two
predictors might be suitable for treatment without prophylactic LCLN dissection.
PMID- 29350103
TI - Society for the History of Alchemy and Chemistry Award Scheme 2018.
PMID- 29350104
TI - The importance of perfusion index monitoring in evaluating the efficacy of
stellate ganglion blockage treatment in Raynaud's disease.
AB - Stellate ganglion blockage (SGB) is a method used for treating Raynaud's
phenomenon (RP). This study primarily aimed to determine whether the perfusion
index (PI) can be used an alternative to Horner's signs in evaluating the
efficacy of SGB in patients diagnosed with RP. In a total of 40 patients, aged 18
65 years and diagnosed with primary RP, SGB was applied for 5 days on the same
side with the 2-finger method, using 6 mL of 5% levobupivacaine at the 7th
cervical vertebra level. The PI values were recorded from the distal end of the
2nd finger of the upper extremity on the side applied with the block at baseline
and at 5, 15, 30, 60 and 120 min. The onset time of Horner findings was recorded.
The PI values and visual analogue scale (VAS) pain scores were recorded pre
treatment and after 2 weeks.When the PI values of the 40 patients were examined,
a 62.7% increase was observed from baseline to the first session at 5 min (p <
0.05). When all sessions were evaluated, a statistically significant increase was
determined in the PI values measured at 5, 15, 30, 60 and 120 min compared with
the baseline PI values. There was a statistically significant decrease in the
post-treatment VAS pain scores and a statistically significant increase in the
post-treatment PI values (p < 0.05). By eliminating peripheral vasospasm with the
application of SGB in patients with RP, the distal artery blood flow and PI are
increased. PI measurement is a more objective method and therefore could be used
as an alternative to Horner findings in evaluating the success of SGB. PI is a
non-invasive and simple measurement and also an earlier indicator in evaluating
the success of SGB than Horner's signs.
PMID- 29350105
TI - Persistent modification of cognitive control through attention training.
AB - An important aspect of cognitive control is to direct attention towards relevant
information and away from distracting information. This attentional modulation is
at the core of several influential frameworks, but its trainability and
generalisability remain unclear. To address this issue, two groups of subjects
were invited to the lab on three consecutive days. On Day 2, they performed an
arrow priming task which trained them to adopt an attentional bias towards (prime
attended group) or away from (prime-diverted group) a potentially conflicting
prime. Direct generalisation of the attention training was measured by assessing
task performance on the same task without the attentional manipulation directly
after training (Day 2) and the next day (Day 3), and comparing it to baseline
(Day 1). Performance on this direct transfer task showed a difference in
attentional modulation between groups directly after training that persisted the
next day. No cross-task generalisation was found to two other tasks that were
closely or more remotely related to the trained task. Together, these results are
in accordance with cognitive control frameworks that limit attentional modulation
to the specific features of the trained task.
PMID- 29350106
TI - Cross-cultural differences in adult Theory of Mind abilities: A comparison of
native-English speakers and native-Chinese speakers on the Self/Other
Differentiation task.
AB - Theory of Mind (ToM) refers to the ability to compute and attribute mental states
to ourselves and other people. It is currently unclear whether ToM abilities are
universal or whether they can be culturally influenced. To address this question,
this research explored potential differences in engagement of ToM processes
between two different cultures, Western (individualist) and Chinese
(collectivist), using a sample of healthy adults. Participants completed a
computerised false-belief task, in which they attributed beliefs to either
themselves or another person, in a matched design, allowing direct comparison
between "Self"- and "Other"-oriented conditions. Results revealed that both
native-English speakers and native-Chinese individuals responded significantly
faster to self-oriented than other-oriented questions. Results also showed that
when a trial required a "perspective-shift," participants from both cultures were
slower to shift from Self-to-Other than from Other-to-Self. Results indicate that
despite differences in collectivism scores, culture does not influence task
performance, with similar results found for both Western and non-Western
participants, suggesting core and potentially universal similarities in the ToM
mechanism across these two cultures.
PMID- 29350107
TI - The effects of ethnicity, musicianship, and tone language experience on pitch
perception.
AB - Language and music are intertwined: music training can facilitate language
abilities, and language experiences can also help with some music tasks. Possible
language-music transfer effects are explored in two experiments in this study. In
Experiment 1, we tested native Mandarin, Korean, and English speakers on a pitch
discrimination task with two types of sounds: speech sounds and fundamental
frequency (F0) patterns derived from speech sounds. To control for factors that
might influence participants' performance, we included cognitive ability tasks
testing memory and intelligence. In addition, two music skill tasks were used to
examine general transfer effects from language to music. Prior studies showing
that tone language speakers have an advantage on pitch tasks have been taken as
support for three alternative hypotheses: specific transfer effects, general
transfer effects, and an ethnicity effect. In Experiment 1, musicians
outperformed non-musicians on both speech and F0 sounds, suggesting a music-to
language transfer effect. Korean and Mandarin speakers performed similarly, and
they both outperformed English speakers, providing some evidence for an ethnicity
effect. Alternatively, this could be due to population selection bias. In
Experiment 2, we recruited Chinese Americans approximating the native English
speakers' language background to further test the ethnicity effect. Chinese
Americans, regardless of their tone language experiences, performed similarly to
their non-Asian American counterparts in all tasks. Therefore, although this
study provides additional evidence of transfer effects across music and language,
it casts doubt on the contribution of ethnicity to differences observed in pitch
perception and general music abilities.
PMID- 29350108
TI - The role of stimulus comparison in animal perceptual learning: Effects of a
distractor placement.
AB - Research on perceptual learning shows that the way stimuli are presented leads to
different outcomes. The intermixed/blocked (I/B) effect is one of these outcomes,
and different mechanisms have been proposed to explain it. In human research, it
seems that comparison between stimuli is important, and the placement of a
distractor between the pre-exposed stimuli interferes with the effect. Results
from animal research are usually interpreted in different terms because the type
of procedure normally used in animal perceptual learning does not favour
comparison. In our experiments, we explore the possibility that a distractor
placed between the to-be-discriminated stimuli may interfere with the perceptual
learning process in rats. In Experiment 1, two flavoured solutions are presented
in an I/B fashion, with a short time lapse between them to favour comparison,
showing the typical I/B effect. In Experiment 2, we introduced a distractor in
between the solutions, abolishing this effect. Experiment 3 further replicates
this by comparing two intermixed groups with or without distractor. The results
replicate the findings from human research, suggesting that comparison also plays
an important role in animal perceptual learning.
PMID- 29350110
TI - Construct validity of the resistance training skills battery in children aged 7
10 years.
AB - The current study sought to examine the construct validity of the Resistance
Training Skills Battery for Children (RTSBc), a movement screen purported to
assess resistance training skill in children. Children aged 7-10 years (n = 27,
21 males, 6 females) undertook measures of resistance training skill via the
RTSBc, motor competence and muscular fitness. Using a median split for RTSBc
scores, children were categorised as high or low resistance training competence.
Univariate ANCOVAs, controlling for maturation, were used to examine whether
measures of muscular fitness and motor competence scores differed as a function
of RTSBc competence. Children who were classified as high for resistance training
competence had significantly better motor competence (P = .001) and significantly
faster 10 m sprint speed (P = .001). However, medicine ball throw and standing
long jump scores as well as peak and average isokinetic muscle strength did not
differ as a function of RTSBc (P > 0.05). In all cases maturation was significant
as a covariate. This study is the first to demonstrate construct validity of the
RTSBc as a measure of general motor competence and sprint speed, but not
strength, in children aged 7-10 years.
PMID- 29350109
TI - Tertiary Care Experience of Sorafenib in the Treatment of Progressive Radioiodine
Refractory Differentiated Thyroid Carcinoma: A Korean Multicenter Study.
AB - BACKGROUND: Sorafenib, a multi-kinase inhibitor, is approved for the treatment of
patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer
(DTC). This study evaluated the efficacy and safety of sorafenib in real-world
clinical practice and compared the results to those of the DECISION trial. The
clinical features associated with better clinical outcomes after sorafenib
treatment were also evaluated. METHODS: This multicenter, retrospective cohort
study evaluated 98 patients with progressive RAI-refractory DTC who were treated
with sorafenib in six tertiary hospitals in Korea. The primary objective was the
progression-free survival (PFS) according to Response Evaluation Criteria In
Solid Tumors v1.1. Overall survival, response rate (defined as the best objective
response according to Response Evaluation Criteria In Solid Tumors v1.1), and
safety were also evaluated. RESULTS: The median PFS was 9.7 months; median
overall survival was not reached during follow-up. Partial responses and stable
disease were achieved in 25 (25%) and 64 (65%) patients, respectively. Stable
disease of >6 months was achieved in 41 (42%) patients. Subgroup analyses
identified several prognostic indicators of a better PFS: absence of disease
related symptoms (hazard ratio [HR] = 0.5; p = 0.041), lung-only metastasis (HR =
0.4; p = 0.048), a daily maintenance dose >=600 mg (HR = 0.3; p = 0.005), and a
thyroglobulin reduction >=60% (HR = 0.4; p = 0.012). The mean daily dose of
sorafenib was 666 +/- 114 mg, and drug withdrawals due to adverse events (AEs)
occurred in 13% of patients. AEs and serious AEs were reported in 93 (95%) and 40
(41%) patients, respectively. The most frequent AE was hand-foot skin reaction
(76%). CONCLUSIONS: The PFS of progressive RAI-refractory DTC patients treated
with sorafenib was consistent with the findings of the DECISION trial. Disease
related symptoms, lung-only metastasis, a daily maintenance dose, and
thyroglobulin reduction were significantly associated with PFS. These results
suggest that sorafenib is an effective treatment option for patients with
progressive RAI-refractory DTC.
PMID- 29350111
TI - Sustained viral suppression with co-administration of oxcarbazepine and
dolutegravir.
AB - Co-administration of dolutegravir and oxcarbazepine has been reported to reduce
levels of dolutegravir and therefore is contraindicated due to insufficient data
to make dosing recommendations. We present eight cases in which patients with
human immunodeficiency virus (HIV) inadvertently received oxcarbazepine while
concurrently receiving 50 mg of dolutegravir daily as part of their
antiretroviral therapy. Upon further evaluation, lab results revealed that
despite the risk of decreased levels of dolutegravir due to possible
oxcarbazepine enzyme induction, patients maintained at or near virologic
suppression (viral load <20 copies/ml). Suppression was maintained in patients
virally suppressed prior to oxcarbazepine initiation as well as in patients
receiving high doses of oxcarbazepine (>1200 mg). All patients self-reported
complete adherence to oxcarbazepine and dolutegravir. Furthermore, careful review
of additional patient medications suggested no other identifiable drug
interactions that could have affected their antiretroviral therapy. This case
series suggests that despite the well-documented drug interaction, concomitant
administration of oxcarbazepine and dolutegravir in the clinical setting did not
adversely affect viral suppression in patients with HIV.
PMID- 29350112
TI - A comparison of HIV-risk behaviors between young black cisgender men who have sex
with men and young black transgender women who have sex with men.
AB - This study compared sexually transmitted infection (STI)-associated risks between
young Black cisgender men who have sex with men (YBMSM) and young Black
transwomen who have sex with men (YBTWSM). Comparisons pertained to: (1)
prevalence of infections; (2) sexual risk; (3) partner-related risks; and (4)
socioeconomic marginalization. YBMSM (n = 577) and YBTWSM (n = 32) were recruited
from an STI clinic in the USA. Volunteers completed a computer-assisted self
interview and medical records were abstracted for STI/HIV information.
Significantly greater prevalence of pharyngeal Chlamydia ( P < .001) and
pharyngeal gonorrhea ( P = .04) occurred among YBTWSM; however, both associations
were moderated and only significant for HIV-uninfected volunteers. YBTWSM had
more oral sex partners and more frequent engagement in oral sex. The number of
new sex partners for anal receptive sex was greater in YBTWSM. YBTWSM were more
likely to exchange sex for money/drugs ( P < .001), have sex with men recently in
prison ( P < .001), who were "anonymous" ( P = .004), or who were "one night
stands" ( P < .001). YBTWSM were more likely to depend on sex partners for money
food, etc. ( P < .001), to miss meals due to lack of money ( P = .01), and to
report having ever being incarcerated ( P = .009). Compared to cisgender YBMSM,
YBTWSM experience multiple risk factors relative to the acquisition/transmission
of STIs and HIV.
PMID- 29350113
TI - Asymptomatic urethral lymphogranuloma venereum: a case report.
AB - Since 2003, there has been a resurgence of lymphogranuloma venereum (LGV), a
variant of Chlamydia trachomatis (CT), among men who have sex with men (MSM) in
several urban areas of Europe and North America. LGV infection occurs most often
at anal sites causing proctitis. Urethral and oropharyngeal infections are rare.
In Quebec, LGV incidence has been increasing exponentially in recent years and
the current guidelines support systematic LGV genotype testing among anorectal CT
positive samples only. This case report describes a patient with a urethral LGV
infection, remarkable due to its prolonged asymptomatic development prior to the
manifestation of an inguinal bubo. Physicians should be vigilant of potential
cases of LGV and forward CT-positive samples occurring among individuals with LGV
risk factors for genotype testing.
PMID- 29350114
TI - The influence of solid retention time on IFAS-MBR systems: analysis of system
behavior.
AB - A University of Cape Town Integrated Fixed-Film Activated Sludge Membrane
Bioreactor (UCT-IFAS-MBR) pilot plant was operated at different values of the
sludge retention time (SRT). Three SRTs were investigated at different durations:
indefinitely, 30 and 15 days. The organic carbon, nitrogen and phosphorus
removal, kinetic/stoichiometric parameters, membrane fouling tendency and sludge
filtration properties were assessed. The findings showed that by decreasing the
SRT, the pilot plant could maintain excellent carbon removal efficiencies
throughout the experiments. In contrast, the biological carbon removal showed a
slight nitrification and was slightly affected by the decrease of the SRT,
showing high performance (approximately 91%, on average). Thus, the biofilm might
have helped sustain the nitrification throughout the experiments. The average
phosphorus removal performance increased slightly with a decrease in SRT,
achieving the maximum efficiency (61.5%) at a SRT of 15 days. After a 30-day SRT,
an increase in resistance due to pore blocking and a general worsening of the
membrane filtration properties occurred.
PMID- 29350115
TI - [Haemolysis: role of the direct antiglobulin test and eluate].
AB - Haemolytic anaemia is the result of an abnormal breakdown of red blood cells. The
direct antiglobulin test (DAT), also known as the direct Coombs test, can be used
to determine the cause of the haemolysis. The DAT distinguishes between immune
and non-immune causes of haemolysis. However, the DAT should not be used in
screening for haemolysis. When the DAT is performed without an indication for in
vivo haemolysis, there is a high risk of false-positive results. To increase the
specificity of the DAT, the eluate can be tested to determine the specificity of
the autoantibodies. In this article we present two cases of haemolytic anaemia in
which the DAT gives further indication of the cause of haemolysis.
PMID- 29350116
TI - [Upper abdominal pain after an elective aortic valve replacement].
AB - A 69-year-old man came to our emergency department with nausea, vomiting and
upper abdominal pain under the suspicion of an ileus. Four weeks before he had
had an elective aortic valve replacement. The basal thoracic slides of the
abdominal CT-scan revealed a significant amount of pericardial effusion, after
which the patient was referred for emergency cardiac surgery. Abdominal
complaints are rarely the primary symptoms of severe heart failure.
PMID- 29350117
TI - [Treating poisoning; how do you choose the best type of gastrointestinal
decontamination?]
AB - - A new guideline: 'Intoxication: initial approach in the hospital' will be
published this year. This guideline sets out the latest insights on
gastrointestinal decontamination in intoxication; the advice is summarized in a
flowchart.- The advice is to generally administer activated charcoal, unless
there are indications that the toxin will not bind to activated charcoal or that
the amount of toxin that the patient has ingested is too great; in these cases
gastric lavage can be considered.- Activated charcoal can be administered up to 2
hours after the ingestion of a toxic substance, unless there are contra
indications. Multiple-dose activated charcoal in combination with a laxative can
be administered in cases of overdose with toxins that use the enterohepatic
circulation (such as theophylline, carbamazepine, quinine, dapsone and
phenobarbital).- Gastric lavage should be limited to extremely serious
intoxication, when the substance has been ingested less than 1-2 hours
previously.- Whole-bowel irrigation should not be performed routinely but should
be limited to ingestion of toxins with sustained release or enteric coating, or
for toxins that do not bind to activated charcoal.
PMID- 29350118
TI - [Online tool to prepare patient for colonoscopy; development and implementation
of a patient-education app].
AB - Optimal patient education prior to colonoscopy is essential for an optimal
outcome of the procedure. Patients benefit from adequate information regarding
laxatives, risks and alternatives, and must provide informed consent. The
endoscopist also has to have access to patient data in advance of the procedure
in order to carry out an adequate risk assessment for the use of sedation. Most
centres in the Netherlands usually make use of a pre-endoscopy consultation to
exchange this information, but here is now pressure on this practice because the
number of colonoscopies is increasing rapidly as a result of the introduction of
the national screening programme for colorectal cancer.
PMID- 29350119
TI - [Medication-overuse headache].
AB - - Medication-overuse headache is a highly prevalent disorder with a major impact
on the quality of life.- Medication-overuse headache is defined as headache on >=
15 days per month with overuse of acute headache medication for >= 3 months. We
talk about overuse in case of intake of simple analgesics on >= 15 days per month
or triptans or combinations of analgesics on >= 10 days per month.- The
underlying type of headache is usually migraine or tension-type headache.- One of
the possible underlying mechanisms of medication-overuse headache is changed
sensitivity as a consequence of central sensitisation.- The initial treatment is
detoxification of the headache medication. The preferred detoxification method is
outpatient, abrupt withdrawal of all acute-headache medication and caffeine
containing products. Essential for successful detoxification is education about
the reasons for detoxification, the expected course and the subsequent treatment.
PMID- 29350120
TI - [Continued development of drugs: the path of thioguanine].
AB - Continued development of existing drugs ('drug rediscovery') may offer new
therapeutic options and be cost-effective. Rediscovered drugs are commonly
prescribed off-label, although licensing can be important to allow safe and
controlled prescription of the drugs to patients. Licensing of a new indication
for a generic drug, however, is a complicated process since there is no blueprint
for this and there is little interest from the pharmaceutical industry due to an
unattractive cost-recovery model. In this article, we illustrate the successful
license-extension for thioguanine - initially developed in 1950 for leukaemia -
as a new treatment for patients with inflammatory bowel disease.
PMID- 29350121
TI - [A boy with involuntary movements].
AB - A 12-year-old Dutch boy came to the paediatrician with involuntary movements of
the right half of his body. He was diagnosed with Sydenham chorea as a
consequence of acute rheumatic fever. Acute rheumatic fever is a rare disease in
Western countries and should be recognised in time. Antibiotic prophylaxis is
indicated in patients who have had acute rheumatic fever, at least until the age
of 40.
PMID- 29350122
TI - [An African boy with haematuria].
AB - An 8-year-old, Senegalese boy presented with a history of painless macroscopic
haematuria. The diagnosis schistosomiasis was made, based on the urine sediment
that revealed eggs from the trematode parasite Schistosoma haematobium. The
patient was treated with praziquantel and made a full recovery.
PMID- 29350123
TI - [DoNTRuN a neurosurgical trainee network; network for the advancement of clinical
research].
AB - There is a lot of research into the effectiveness of interventions, but good
evidence for many interventions is missing. This is very true of simple and
frequently performed treatments. These interventions are often done by trainees
in the course of their specialist training, and for this reason they are in a
unique position to carry out research into them. There are far fewer high
quality, multicentre clinical trials in the surgical specialisations than in any
other specialisation. As trainee neurosurgeons, we are of the opinion that this
can be improved upon. With the establishment of the Dutch Neurosurgical Trainee
Research Network (DoNTRuN), a national network, we are aiming to initiate and
carry out new clinical trials. This initiative, which is currently unique in the
Netherlands, will not only enable us to set up multicentre clinical trials
relatively simply, but will also educate trainees in the carrying out of thorough
clinical research, an area neglected in the current training program.
PMID- 29350125
TI - Current management: migraine headache.
AB - Migraine varies in its frequency, severity, and impact; treatment should consider
these variations and the patient's needs and goals. Migraine pharmacologic
treatment may be acute (abortive) or preventive (prophylactic), and patients
often require both. New medication devices are available or in development,
including an intracutaneous, microneedle system of zolmitriptan and sumatriptan,
and breath-powered powder sumatriptan intranasal treatment. Lasmiditan, a 5-HT1F
receptor agonist, is in development for acute treatment, as are small molecule
calcitonin gene-related peptide (CGRP) receptor antagonists (Gepants) for acute
and preventive treatment. Antibodies to CGRP and its receptor are being developed
for migraine prevention. All 4 treatments are effective and have, as of yet, no
safety concerns.
PMID- 29350124
TI - A dimensional approach to assessing psychiatric risk in adults born very preterm.
AB - BACKGROUND: Individuals who were born very preterm have higher rates of
psychiatric diagnoses compared with term-born controls; however, it remains
unclear whether they also display increased sub-clinical psychiatric
symptomatology. Hence, our objective was to utilize a dimensional approach to
assess psychiatric symptomatology in adult life following very preterm birth.
METHODS: We studied 152 adults who were born very preterm (before 33 weeks'
gestation; gestational range 24-32 weeks) and 96 term-born controls.
Participants' clinical profile was examined using the Comprehensive Assessment of
At-Risk Mental States (CAARMS), a measure of sub-clinical symptomatology that
yields seven subscales including general psychopathology, positive, negative,
cognitive, behavioural, motor and emotional symptoms, in addition to a total
psychopathology score. Intellectual abilities were examined using the Wechsler
Abbreviated Scale of Intelligence. RESULTS: Between-group differences on the
CAARMS showed elevated symptomatology in very preterm participants compared with
controls in positive, negative, cognitive and behavioural symptoms. Total
psychopathology scores were significantly correlated with IQ in the very preterm
group only. In order to examine the characteristics of participants' clinical
profile, a principal component analysis was conducted. This revealed two
components, one reflecting a non-specific psychopathology dimension, and the
other indicating a variance in symptomatology along a positive-to-negative
symptom axis. K-means (k = 4) were used to further separate the study sample into
clusters. Very preterm adults were more likely to belong to a high non-specific
psychopathology cluster compared with controls.Conclusion and RelevanceVery
preterm individuals demonstrated elevated psychopathology compared with full-term
controls. Their psychiatric risk was characterized by a non-specific clinical
profile and was associated with lower IQ.
PMID- 29350126
TI - A review of the neurobiology of obesity and the available pharmacotherapies.
AB - Obesity is becoming an increasing problem worldwide. In addition to causing many
physical health consequences, there is increasing evidence demonstrating that
obesity is toxic to the brain and, as such, can be considered a disease of the
central nervous system. Peripheral level regulators of appetite, such as leptin,
insulin, ghrelin, and cholecystokinin, feed into the appetite center of the
brain, which is controlled by the hypothalamus, to maintain homeostasis and
energy balance. However, food consumption is not solely mediated by energy
balance, but is also regulated by the mesolimbic reward system, where motivation,
reward, and reinforcement factors influence obesity. The purpose of this review
is to highlight the neurobiology of eating behavior and obesity and to describe
various neurobiological treatment mechanisms to treat obesity.
PMID- 29350127
TI - Converting oral to long-acting injectable antipsychotics: a guide for the
perplexed.
AB - There has been increasing recognition that antipsychotic nonadherence is common
across all stages of schizophrenia, starting from the first episode. Moreover,
numerous meta-analyses of the existing literature indicate superiority of long
acting injectable (LAI) over oral antipsychotics when one adjusts for the greater
illness severity and duration among patients in LAI antipsychotic trials. The
increasing availability of LAI antipsychotic options has raised interest in
converting patients from oral medication; however, the successful transition from
oral to the comparable LAI antipsychotic requires an understanding of the current
extent of antipsychotic exposure, the kinetics of the LAI preparation, and the
expected plasma levels achieved by the LAI formulation. The purpose of this
article is to provide, in a concise format, the essential information for
converting patients to the LAI forms of haloperidol, fluphenazine, risperidone,
paliperidone, olanzapine, and aripiprazole from the comparable oral medication,
and how the use of plasma antipsychotic levels can be invaluable for this
process.
PMID- 29350128
TI - Between a rock-a-bye and a hard place: mood disorders during the peripartum
period.
AB - Mood disorders including major depressive disorder and bipolar disorder are
common during and after pregnancy. Timely identification and appropriate
management of mood episodes is essential to maximize maternal well-being and
minimize adverse outcomes. Failure to do so results in maternal suffering and
impaired child bonding, and has the potential for devastating outcomes including
suicide and infanticide. Women are routinely screened for unipolar depression
during or after pregnancy but not for bipolar disorder, in spite of the fact that
childbirth is associated with a major risk for onset or exacerbation of bipolar
disorder. Delays in detection as well as misdiagnosis of bipolar disorder as
major depressive disorder may put women at risk of many adverse consequences,
including symptom exacerbation, psychiatric hospitalization, and suicide. A
thorough psychiatric assessment is necessary to establish diagnosis, to address
safety issues, and to formulate a treatment plan. Treatment of mood disorders
during pregnancy is complicated by the potential risks of fetal exposure to
psychotropic medications, and the use of these medications during the postpartum
period may result in infant medication exposure through breastmilk. These risks
of psychotropic medication exposure must be weighed against the risk of untreated
mood disorders. This review will discuss the pathophysiology, epidemiology,
diagnosis, and treatment of mood disorders during pregnancy and the postpartum
period. Screening tools that can be used in the primary care and obstetrics
settings to assist in identifying women with peripartum mood disorders will also
be discussed.
PMID- 29350129
TI - New medications for treatment-resistant depression: a brief review of recent
developments.
AB - There is a great unmet need for new medications with novel mechanisms of action
that can effectively treat patients who do not benefit from standard
antidepressant therapies. After a period in which it seemed as if the
pharmaceutical pipeline for new antidepressants was going dry, the past decade
has witnessed renewed interest, beginning with discovery of the antidepressant
effects of ketamine. This article briefly highlights more recent research on
ketamine and other investigational antidepressants.
PMID- 29350130
TI - Ecology and Evolution of Chromosomal Gene Transfer between Environmental
Microorganisms and Pathogens.
AB - Inspection of the genomes of bacterial pathogens indicates that their pathogenic
potential relies, at least in part, on the activity of different elements that
have been acquired by horizontal gene transfer from other (usually unknown)
microorganisms. Similarly, in the case of resistance to antibiotics, besides
mutation-driven resistance, the incorporation of novel resistance genes is a
widespread evolutionary procedure for the acquisition of this phenotype. Current
information in the field supports the idea that most (if not all) genes acquired
by horizontal gene transfer by bacterial pathogens and contributing to their
virulence potential or to antibiotic resistance originate in environmental, not
human-pathogenic, microorganisms. Herein I discuss the potential functions that
the genes that are dubbed virulence or antibiotic resistance genes may have in
their original hosts in nonclinical, natural ecosystems. In addition, I discuss
the potential bottlenecks modulating the transfer of virulence and antibiotic
resistance determinants and the consequences in terms of speciation of acquiring
one or another of both categories of genes. Finally, I propose that exaptation, a
process by which a change of function is achieved by a change of habitat and not
by changes in the element with the new functionality, is the basis of the
evolution of virulence determinants and of antibiotic resistance genes.
PMID- 29350131
TI - Antimicrobial Resistance in Stenotrophomonas spp.
AB - Bacteria of the genus Stenotrophomonas are found throughout the environment, in
close association with soil, sewage, and plants. Stenotrophomonas maltophilia,
the first member of this genus, is the predominant species, observed in soil,
water, plants, animals, and humans. It is also an opportunistic pathogen
associated with the increased number of infections in both humans and animals in
recent years. In this article, we summarize all Stenotrophomonas species (mainly
S. maltophilia) isolated from animals and food products of animal origin and
further distinguish all isolates based on antimicrobial susceptibility and
resistance phenotypes. The various mechanisms of both intrinsic and acquired
antimicrobial resistance, which were mainly identified in S. maltophilia isolates
of nosocomial infections, have been classified as follows: multidrug efflux
pumps; resistance to beta-lactams, aminoglycosides, quinolones, trimethoprim
sulfamethoxazole, and phenicols; and alteration of lipopolysaccharide and two
component regulatory systems. The dissemination, coselection, and persistence of
resistance determinants among S. maltophilia isolates have also been elaborated.
PMID- 29350132
TI - Toward Forensic Uses of Microbial Source Tracking.
AB - The science of microbial source tracking has allowed researchers and watershed
managers to go beyond general indicators of fecal pollution in water such as
coliforms and enterococci, and to move toward an understanding of specific
contributors to water quality issues. The premise of microbial source tracking is
that characteristics of microorganisms that are strongly associated with
particular host species can be used to trace fecal pollution to particular animal
species (including humans) or groups, e.g., ruminants or birds. Microbial source
tracking methods are practiced largely in the realm of research, and none are
approved for regulatory uses on a federal level. Their application in the
conventional sense of forensics, i.e., to investigate a crime, has been limited,
but as some of these methods become standardized and recognized in a regulatory
context, they will doubtless play a larger role in applications such as total
maximum daily load assessment, investigations of sewage spills, and contamination
from agricultural practices.
PMID- 29350133
TI - Borrelia miyamotoi Infections in Humans and Ticks, Northeastern China.
AB - We conducted an investigation of Borrelia miyamotoi infections in humans and
ticks in northeastern China. Of 984 patients reporting recent tick bites, 14
(1.4%) were found to be infected with B. miyamotoi by PCR and genomic sequencing.
The 14 patients had nonspecific febrile manifestations, including fever,
headache, anorexia, asthenia, and arthralgia. Rash, eschar, and regional
lymphadenopathy were each observed in 1 patient. Four (28.6%) patients were
hospitalized because of severe disease. B. miyamotoi was detected in 3.0%
(19/627) of Ixodes persulcatus, 1 (2.8%) of 36 Haemaphysalis concinna, and none
of 29 Dermacentor silvarum ticks. Phylogenetic analyses based on sequences of a
nearly entire 16s rRNA gene, a partial flagellin gene, and the
glycerophosphodiester phosphodiesterase gene revealed that B. miyamotoi
identified in patients and ticks were clustered in the group of the Siberian
type. These findings indicate that B. miyamotoi is endemic in northeastern China
and its public health significance deserves further investigation.
PMID- 29350134
TI - Hypervirulent Klebsiella pneumoniae in Cryptogenic Liver Abscesses, Paris,
France.
AB - Liver abscesses containing hypervirulent Klebsiella pneumoniae have emerged
during the past 2 decades, originally in Southeast Asia and then worldwide. We
hypothesized that hypervirulent K. pneumoniae might also be emerging in France.
In a retrospective, monocentric, cohort study, we analyzed characteristics and
outcomes for 199 consecutive patients in Paris, France, with liver abscesses
during 2010-2015. We focused on 31 patients with abscesses containing K.
pneumoniae. This bacterium was present in most (14/27, 52%) cryptogenic liver
abscesses. Cryptogenic K. pneumoniae abscesses were more frequently community
acquired (p<0.00001) and monomicrobial (p = 0.008), less likely to involve cancer
patients (p<0.01), and relapsed less often (p<0.01) than did noncryptogenic K.
pneumoniae liver abscesses. K. pneumoniae isolates from cryptogenic abscesses
belonged to either the K1 or K2 serotypes and had more virulence factors than
noncryptogenic K. pneumoniae isolates. Hypervirulent K. pneumoniae are emerging
as the main pathogen isolated from cryptogenic liver abscesses in the study area.
PMID- 29350135
TI - Plasmid-Encoded Transferable mecB-Mediated Methicillin Resistance in
Staphylococcus aureus.
AB - During cefoxitin-based nasal screening, phenotypically categorized methicillin
resistant Staphylococcus aureus (MRSA) was isolated and tested negative for the
presence of the mecA and mecC genes as well as for the SCCmec-orfX junction
region. The isolate was found to carry a mecB gene previously described for
Macrococcus caseolyticus but not for staphylococcal species. The gene is flanked
by beta-lactam regulatory genes similar to mecR, mecI, and blaZ and is part of an
84.6-kb multidrug-resistance plasmid that harbors genes encoding additional
resistances to aminoglycosides (aacA-aphD, aphA, and aadK) as well as macrolides
(ermB) and tetracyclines (tetS). This further plasmidborne beta-lactam resistance
mechanism harbors the putative risk of acceleration or reacceleration of MRSA
spread, resulting in broad ineffectiveness of beta-lactams as a main therapeutic
application against staphylococcal infections.
PMID- 29350136
TI - Ecologic Features of Plague Outbreak Areas, Democratic Republic of the Congo,
2004-2014.
AB - During 2004-2014, the Democratic Republic of the Congo (DRC) declared 54% of
plague cases worldwide. Using national data, we characterized the epidemiology of
human plague in DRC for this period. All 4,630 suspected human plague cases and
349 deaths recorded in DRC came from Orientale Province. Pneumonic plague cases
(8.8% of total) occurred during 2 major outbreaks in mining camps in the
equatorial forest, and some limited outbreaks occurred in the Ituri highlands.
Epidemics originated in 5 health zones clustered in Ituri, where sporadic bubonic
cases were recorded throughout every year. Classification and regression tree
characterized this cluster by the dominance of ecosystem 40 (mountain tropical
climate). In conclusion, a small, stable, endemic focus of plague in the
highlands of the Ituri tropical region persisted, acting as a source of outbreaks
in DRC.
PMID- 29350137
TI - Multiplex PCR-Based Next-Generation Sequencing and Global Diversity of Seoul
Virus in Humans and Rats.
AB - Seoul virus (SEOV) poses a worldwide public health threat. This virus, which is
harbored by Rattus norvegicus and R. rattus rats, is the causative agent of
hemorrhagic fever with renal syndrome (HFRS) in humans, which has been reported
in Asia, Europe, the Americas, and Africa. Defining SEOV genome sequences plays a
critical role in development of preventive and therapeutic strategies against the
unique worldwide hantavirus. We applied multiplex PCR-based next-generation
sequencing to obtain SEOV genome sequences from clinical and reservoir host
specimens. Epidemiologic surveillance of R. norvegicus rats in South Korea during
2000-2016 demonstrated that the serologic prevalence of enzootic SEOV infections
was not significant on the basis of sex, weight (age), and season. Viral loads of
SEOV in rats showed wide dissemination in tissues and dynamic circulation among
populations. Phylogenetic analyses showed the global diversity of SEOV and
possible genomic configuration of genetic exchanges.
PMID- 29350138
TI - Increase in Ocular Syphilis Cases at Ophthalmologic Reference Center, France,
2012-2015.
AB - We describe the frequency, demographic and clinical features, and visual outcomes
of ocular syphilis infections observed during 2012-2015 at a tertiary reference
center in Paris, France. Twenty-one cases (29 eyes) were identified. The
occurrence of ocular syphilis increased from 1 case in 2012 to 5 cases in 2013, 6
cases in 2014, and 9 cases in 2015 (2.22-25.21/1,000 individual patients/year for
the period). Among case-patients, an annual 20%-33% were co-infected with HIV.
Seventy-six percent of ocular syphilis infections occurred in men who have sex
with men. Seventy-five percent of case-patients had a good final visual outcome
(best-corrected visual acuity >0.3 logMAR score). Visual outcome was worse for
HIV-positive patients than for HIV-negative patients (p = 0.0139). At follow-up,
the best visual outcomes were observed in patients whose mean time from first
ocular symptom to consultation was 15 days (SD +19 days).
PMID- 29350139
TI - Echinococcus spp. Tapeworms in North America.
AB - Alveolar and cystic echinococcosis are emerging and reemerging in Europe, Africa,
and Asia. The expansion of Echinococcus spp. tapeworms in wildlife host
reservoirs appears to be driving this emergence in some areas. Recent studies
suggest a similar phenomenon may be occurring in North America. We describe the
context of Echinococcus spp. research in North America, with a specific focus on
the contiguous United States. Although studies were conducted in the United
States throughout the 1900s on various sylvatic and domestic Echinococcus spp.
tapeworm cycles, data are lacking for the past ~30 years. We review previous
research, provide analysis of more recent focal studies, and suggest that
Echinococcus spp. tapeworms, in particular E. canadensis, may be underrecognized.
As a result, we suggest that additional research and surveillance be conducted
for these tapeworms in wildlife host reservoirs across the United States.
PMID- 29350140
TI - Co-circulation of Influenza A H5, H7, and H9 Viruses and Co-infected Poultry in
Live Bird Markets, Cambodia.
AB - Longitudinal surveillance of 2 live bird markets in Cambodia revealed year-round,
high co-circulation of H5, H7, and H9 influenza viruses. We detected influenza A
viruses in 51.3% of ducks and 39.6% of chickens, and co-infections, mainly by H5
and H9 viruses, in 0.8% of ducks and 4.5% of chickens.
PMID- 29350141
TI - Spread of Meropenem-Resistant Streptococcus pneumoniae Serotype 15A-ST63 Clone in
Japan, 2012-2014.
AB - After the introduction of pneumococcal conjugate vaccines, the incidence of
pneumococcal infections due to meropenem-resistant serotype 15A-ST63 strains
increased in Japan. By using whole-genome sequencing and comparing sequences with
those of clones from the United Kingdom, the United States, and Canada, we
clarified the traits of the serotype 15A-ST63 clone. Our analysis revealed that
the meropenem-resistant serotype 15A-ST63 strains from Japan originated from
meropenem-susceptible strains from Japan. Recombination site prediction analysis
showed that the meropenem-resistant strain-specific recombination regions
included the pbp1a and pbp2b regions. A detailed analysis of the composition of
these genes indicated that resistance seems to be caused by pbp1a recombination.
The pbp1a gene in meropenem-resistant isolates was identical to that in multidrug
(including meropenem)-resistant serotype 19A-ST320 pneumococci, which have spread
in the United States. The global spread of pneumococci of this lineage is
noteworthy because serotype 15A is not included in the currently used 13-valent
pneumococcal conjugate vaccine.
PMID- 29350142
TI - Lethal Respiratory Disease Associated with Human Rhinovirus C in Wild
Chimpanzees, Uganda, 2013.
AB - We describe a lethal respiratory outbreak among wild chimpanzees in Uganda in
2013 for which molecular and epidemiologic analyses implicate human rhinovirus C
as the cause. Postmortem samples from an infant chimpanzee yielded near-complete
genome sequences throughout the respiratory tract; other pathogens were absent.
Epidemiologic modeling estimated the basic reproductive number (R0) for the
epidemic as 1.83, consistent with the common cold in humans. Genotyping of 41
chimpanzees and examination of 24 published chimpanzee genomes from subspecies
across Africa showed universal homozygosity for the cadherin-related family
member 3 CDHR3-Y529 allele, which increases risk for rhinovirus C infection and
asthma in human children. These results indicate that chimpanzees exhibit a
species-wide genetic susceptibility to rhinovirus C and that this virus,
heretofore considered a uniquely human pathogen, can cross primate species
barriers and threatens wild apes. We advocate engineering interventions and
prevention strategies for rhinovirus infections for both humans and wild apes.
PMID- 29350143
TI - Adenovirus Type 4 Respiratory Infections among Civilian Adults, Northeastern
United States, 2011-20151.
AB - Human adenovirus type 4 (HAdV-4) is most commonly isolated in military settings.
We conducted detailed molecular characterization on 36 HAdV-4 isolates recovered
from civilian adults with acute respiratory disease (ARD) in the northeastern
United States during 2011-2015. Specimens came from college students, residents
of long-term care facilities or nursing homes, a cancer patient, and young adults
without co-morbidities. HAdV-4 genome types 4a1 and 4a2, the variants most
frequently detected among US military recruits in basic training before the
restoration of vaccination protocols, were isolated in most cases. Two novel a
like variants were recovered from students enrolled at a college in Tompkins
County, New York, USA, and a prototype-like variant distinguishable from the
vaccine strain was isolated from an 18-year-old woman visiting a physician's
office in Ulster County, New York, USA, with symptoms of influenza-like illness.
Our data suggest that HAdV-4 might be an underestimated causative agent of ARD
among civilian adults.
PMID- 29350144
TI - Emergomyces africanus in Soil, South Africa.
AB - We detected Emergomyces africanus, a thermally dimorphic fungus that causes an
HIV-associated systemic mycosis, by PCR in 18 (30%) of 60 soil samples from a
wide range of habitats in South Africa. Direct and indirect culture techniques
were unsuccessful. Experimental intraperitoneal inoculation of conidia induced
murine disease.
PMID- 29350145
TI - Development of a Pediatric Ebola Predictive Score, Sierra Leone1.
AB - We compared children who were positive for Ebola virus disease (EVD) with those
who were negative to derive a pediatric EVD predictor (PEP) score. We collected
data on all children <13 years of age admitted to 11 Ebola holding units in
Sierra Leone during August 2014-March 2015 and performed multivariable logistic
regression. Among 1,054 children, 309 (29%) were EVD positive and 697 (66%) EVD
negative, with 48 (5%) missing. Contact history, conjunctivitis, and age were the
strongest positive predictors for EVD. The PEP score had an area under receiver
operating characteristics curve of 0.80. A PEP score of 7/10 was 92% specific and
44% sensitive; 3/10 was 30% specific, 94% sensitive. The PEP score could
correctly classify 79%-90% of children and could be used to facilitate triage
into risk categories, depending on the sensitivity or specificity required.
PMID- 29350146
TI - Macacine Herpesvirus 1 Antibody Prevalence and DNA Shedding among Invasive Rhesus
Macaques, Silver Springs State Park, Florida, USA.
AB - We compiled records on macacine herpesvirus 1 (McHV-1) seroprevalence and, during
2015-2016, collected saliva and fecal samples from the free-ranging rhesus
macaques of Silver Springs State Park, a popular public park in central Florida,
USA, to determine viral DNA shedding and perform sequencing. Phylogenetic
analysis of the US5 and US5-US6 intragenic sequence from free-ranging and
laboratory McHV-1 variants did not reveal genomic differences. In animals
captured during 2000-2012, average annual seroprevalence was 25% +/- 9 (mean +/-
SD). We found 4%-14% (95% CI 2%-29%) of macaques passively sampled during the
fall 2015 mating season shed McHV-1 DNA orally. We did not observe viral shedding
during the spring or summer or from fecal samples. We conclude that these
macaques can shed McHV-1, putting humans at risk for exposure to this potentially
fatal pathogen. Management plans should be put in place to limit transmission of
McHV-1 from these macaques.
PMID- 29350147
TI - Fly Reservoir Associated with Wohlfahrtiimonas Bacteremia in a Human.
AB - Wohlfahrtiimonas species bacteria were isolated from the bloodstream of a patient
with septicemia and wound myiasis. Environmental investigations identified a
Wohlfahrtiimonas sp. among insects in the Americas and in a previously
undescribed vector, the green bottle fly (Lucilia sericata). The isolates
possibly represent a new species within the genus Wohlfahrtiimonas.
PMID- 29350148
TI - Scrub Typhus Outbreak in Chonburi Province, Central Thailand, 2013.
AB - Investigation of a scrub typhus outbreak in Thailand during September 2013 found
that 9.1% of Thai soldiers and 11.1% of residents living in areas surrounding
training sites had antibodies against the causative agent, Orientia
tsutsugamushi. Sequence analysis of O. tsutsugamushi from rodents and chiggers
identified 7 genogroups and 3 genotypes.
PMID- 29350149
TI - Cysticercosis in Shandong Province, Eastern China.
AB - We analyzed demographic and clinical data and estimated the incidence of
cysticercosis in Shandong Province, China, during 1975-2014. Our analyses showed
that a cysticercosis-endemic area is present in Shandong Province, especially in
its western regions. Improved surveillance and control are needed to address the
elevated risk for cysticercosis in this region.
PMID- 29350150
TI - Role of Environmental Factors in Shaping Spatial Distribution of Salmonella
enterica Serovar Typhi, Fiji.
AB - Fiji recently experienced a sharp increase in reported typhoid fever cases. To
investigate geographic distribution and environmental risk factors associated
with Salmonella enterica serovar Typhi infection, we conducted a cross-sectional
cluster survey with associated serologic testing for Vi capsular antigen-specific
antibodies (a marker for exposure to Salmonella Typhi in Fiji in 2013. Hotspots
with high seroprevalence of Vi-specific antibodies were identified in
northeastern mainland Fiji. Risk for Vi seropositivity increased with increased
annual rainfall (odds ratio [OR] 1.26/quintile increase, 95% CI 1.12-1.42), and
decreased with increased distance from major rivers and creeks (OR 0.89/km
increase, 95% CI 0.80-0.99) and distance to modeled flood-risk areas (OR
0.80/quintile increase, 95% CI 0.69-0.92) after being adjusted for age, typhoid
fever vaccination, and home toilet type. Risk for exposure to Salmonella Typhi
and its spatial distribution in Fiji are driven by environmental factors. Our
findings can directly affect typhoid fever control efforts in Fiji.
PMID- 29350151
TI - Risk Communication and Ebola-Specific Knowledge and Behavior during 2014-2015
Outbreak, Sierra Leone.
AB - We assessed the effect of information sources on Ebola-specific knowledge and
behavior during the 2014-2015 Ebola virus disease outbreak in Sierra Leone. We
pooled data from 4 population-based knowledge, attitude, and practice surveys
(August, October, and December 2014 and July 2015), with a total of 10,604
respondents. We created composite variables for exposures (information sources:
electronic, print, new media, government, community) and outcomes (knowledge and
misconceptions, protective and risk behavior) and tested associations by using
logistic regression within multilevel modeling. Exposure to information sources
was associated with higher knowledge and protective behaviors. However, apart
from print media, exposure to information sources was also linked to
misconceptions and risk behavior, but with weaker associations observed.
Knowledge and protective behavior were associated with the outbreak level, most
strongly after the peak, whereas risk behavior was seen at all levels of the
outbreak. In future outbreaks, close attention should be paid to dissemination of
information.
PMID- 29350152
TI - Epidemic Varicella Zoster Virus among University Students, India.
AB - We investigated a yearlong varicella zoster virus outbreak in a highly
susceptible young adult population at a large university in India. Outbreaks of
varicella infection among adults are not well described in the literature.
Infection control measures and vaccination policy for this age group and setting
are needed.
PMID- 29350153
TI - Trends in Infectious Disease Mortality, South Korea, 1983-2015.
AB - We used national statistics from 1983-2015 to evaluate trends in mortality caused
by infectious diseases in South Korea. Age-standardized mortality from infectious
disease decreased from 43.5/100,000 population in 1983 to 16.5/100,000 in 1996,
and then increased to 44.6/100,000 in 2015. Tuberculosis was the most common
cause of death in 1983 and respiratory tract infections in 2015. We observed a
significant decline in infant deaths caused by infectious diseases, but mortality
in persons age >65 years increased from 135 deaths/100,000 population in 1996 to
307/100,000 in 2015. The relative inequality indices for respiratory tract
infections, sepsis, and tuberculosis tended to increase over time. Although
substantial progress has been achieved in terms of infant mortality, death rates
from infectious disease has not decreased overall. Elderly populations with lower
education levels and subgroups susceptible to respiratory infections and sepsis
should be the focus of preventive policies.
PMID- 29350154
TI - Use of Pristinamycin for Macrolide-Resistant Mycoplasma genitalium Infection.
AB - High levels of macrolide resistance and increasing fluoroquinolone resistance are
found in Mycoplasma genitalium in many countries. We evaluated pristinamycin for
macrolide-resistant M. genitalium in a sexual health center in Australia.
Microbiologic cure was determined by M. genitalium-specific 16S PCR 14-90 days
after treatment began. Of 114 persons treated with pristinamycin, infection was
cured in 85 (75%). This percentage did not change when pristinamycin was given at
daily doses of 2 g or 4 g or at 3 g combined with 200 mg doxycycline. In
infections with higher pretreatment bacterial load, treatment was twice as likely
to fail for each 1 log10 increase in bacterial load. Gastrointestinal side
effects occurred in 7% of patients. Pristinamycin at maximum oral dose, or
combined with doxycycline, cured 75% of macrolide-resistant M. genitalium
infections. Pristinamycin is well-tolerated and remains an option where
fluoroquinolones have failed or cannot be used.
PMID- 29350155
TI - Yersinia pestis Survival and Replication in Potential Ameba Reservoir.
AB - Plague ecology is characterized by sporadic epizootics, then periods of dormancy.
Building evidence suggests environmentally ubiquitous amebae act as feral
macrophages and hosts to many intracellular pathogens. We conducted environmental
genetic surveys and laboratory co-culture infection experiments to assess whether
plague bacteria were resistant to digestion by 5 environmental ameba species.
First, we demonstrated that Yersinia pestis is resistant or transiently resistant
to various ameba species. Second, we showed that Y. pestis survives and
replicates intracellularly within Dictyostelium discoideum amebae for ?48 hours
postinfection, whereas control bacteria were destroyed in <1 hour. Finally, we
found that Y. pestis resides within ameba structures synonymous with those found
in infected human macrophages, for which Y. pestis is a competent pathogen.
Evidence supporting amebae as potential plague reservoirs stresses the importance
of recognizing pathogen-harboring amebae as threats to public health,
agriculture, conservation, and biodefense.
PMID- 29350156
TI - Dengue-Associated Posterior Reversible Encephalopathy Syndrome, Vietnam.
AB - Dengue can cause neurologic complications in addition to the more common
manifestations of plasma leakage and coagulopathy. Posterior reversible
encephalopathy syndrome has rarely been described in dengue, although the
pathophysiology of endothelial dysfunction likely underlies both. We describe a
case of dengue-associated posterior reversible encephalopathy syndrome and
discuss diagnosis and management.
PMID- 29350157
TI - Relative Risk for Ehrlichiosis and Lyme Disease Where Vectors for Both Are
Sympatric, Southeastern United States.
PMID- 29350158
TI - Human African Trypanosomiasis in Emigrant Returning to China from Gabon, 2017.
AB - Human African trypanosomiasis is endemic to parts of sub-Saharan Africa and
should be considered in the differential diagnosis of patients who have visited
or lived in Africa. We report a 2017 case of stage 2 Trypanosoma brucei gambiense
disease in an emigrant who returned to China from Gabon.
PMID- 29350159
TI - Clinical and Molecular Epidemiology of Staphylococcal Toxic Shock Syndrome in the
United Kingdom.
AB - Staphylococcal toxic shock syndrome (TSS) was originally described in
menstruating women and linked to TSS toxin 1 (TSST-1)-producing Staphylococcus
aureus. Using UK national surveillance data, we ascertained clinical, molecular
and superantigenic characteristics of TSS cases. Average annual TSS incidence was
0.07/100,000 population. Patients with nonmenstrual TSS were younger than those
with menstrual TSS but had the same mortality rate. Children <16 years of age
accounted for 39% of TSS cases, most caused by burns and skin and soft tissue
infections. Nonmenstrual TSS is now more common than menstrual TSS in the UK,
although both types are strongly associated with the tst+ clonal complex (CC) 30
methicillin-sensitive S. aureus lineage, which accounted for 49.4% of all TSS and
produced more TSST-1 and superantigen bioactivity than did tst+ CC30 methicillin
resistant S. aureus strains. Better understanding of this MSSA lineage and
infections in children could focus interventions to prevent TSS in the future.
PMID- 29350160
TI - Effects of Culling on Leptospira interrogans Carriage by Rats.
AB - We found that lethal, urban rat control is associated with a significant increase
in the odds that surviving rats carry Leptospira interrogans. Our results suggest
that human interventions have the potential to affect and even increase the
prevalence of zoonotic pathogens within rat populations.
PMID- 29350161
TI - Invasive Serotype 35B Pneumococci Including an Expanding Serotype Switch Lineage.
PMID- 29350162
TI - New Parvovirus Associated with Serum Hepatitis in Horses after Inoculation of
Common Biological Product.
AB - Equine serum hepatitis (i.e., Theiler's disease) is a serious and often life
threatening disease of unknown etiology that affects horses. A horse in Nebraska,
USA, with serum hepatitis died 65 days after treatment with equine-origin tetanus
antitoxin. We identified an unknown parvovirus in serum and liver of the dead
horse and in the administered antitoxin. The equine parvovirus-hepatitis (EqPV-H)
shares <50% protein identity with its phylogenetic relatives of the genus
Copiparvovirus. Next, we experimentally infected 2 horses using a tetanus
antitoxin contaminated with EqPV-H. Viremia developed, the horses seroconverted,
and acute hepatitis developed that was confirmed by clinical, biochemical, and
histopathologic testing. We also determined that EqPV-H is an endemic infection
because, in a cohort of 100 clinically normal adult horses, 13 were viremic and
15 were seropositive. We identified a new virus associated with equine serum
hepatitis and confirmed its pathogenicity and transmissibility through
contaminated biological products.
PMID- 29350163
TI - Amebaborne "Attilina massiliensis" Keratitis, France.
AB - We report a case of Acanthamoeba castellani keratitis in a person who wore
contact lenses. The amebae hosted an ameba-resistant bacterial symbiont,
provisionally named "Attilina massiliensis," a yet undescribed alpha
Proteobacterium.
PMID- 29350164
TI - Cerebral Syphilitic Gumma in Immunocompetent Man, Japan.
AB - Although cerebral syphilitic gummas are generally considered to be rare
manifestations of tertiary syphilis, many reports exist of early cerebral
syphilitic gumma. Our finding of cerebral syphilitic gumma in an HIV-negative man
within 5 months after syphilis infection suggests that this condition should be
considered in syphilis patients who have neurologic symptoms.
PMID- 29350165
TI - Novel Streptococcus suis Sequence Type 834 among Humans, Madagascar.
AB - Two cases of meningitis caused by Streptococcus suis occurred in Madagascar, 1 in
2015 and 1 in 2016. We report the characterization of the novel sequence type,
834, which carried the mrp+/sly+/epf+ virulence marker and a mutation G->T at
position 174, leading to a substitution mutS1 to mutS284.
PMID- 29350166
TI - Cronobacter sakazakii Infection from Expressed Breast Milk, Australia.
AB - Cronobacter sakazakii neonatal infections are often epidemiologically linked to
the consumption of contaminated powdered infant formula. We describe a case
resulting from consumption of contaminated expressed breast milk, as confirmed by
whole-genome sequencing. This case highlights potential risks associated with
storage and acquisition of expressed breast milk.
PMID- 29350167
TI - Rickettsia africae and Novel Rickettsial Strain in Amblyomma spp. Ticks,
Nicaragua, 2013.
AB - We report molecular detection of Rickettsia africae in Amblyomma ovale ticks from
Nicaragua and a novel rickettsial strain in an A. triste tick. Of 146 ticks from
dogs, 16.4% were Rickettsia PCR positive. The presence of Rickettsia spp. in
human-biting ticks in Nicaragua may pose a public health concern.
PMID- 29350168
TI - Influenza D Virus in Cattle, Ireland.
AB - We detected influenza D virus in 18 nasal swab samples from cattle in Ireland
that were clinically diagnosed with respiratory disease. Specimens were obtained
from archived samples received for routine diagnosis during 2014-2016. Sequencing
showed that viruses from Ireland clustered with virus sequences obtained in
Europe within the D/swine/OK/1334/2011 clade.
PMID- 29350169
TI - Containment of Highly Pathogenic Avian Influenza A(H5N1) Virus, Lebanon, 20161.
AB - A preparedness plan for avian influenza A(H5N1) virus infection was activated in
Lebanon in 2016 after reported cases in poultry. Exposed persons were given
prophylaxis and monitored daily. A total of 185 exposed persons were identified:
180 received prophylaxis, 181 were monitored, and 41 suspected cases were
reported. All collected specimens were negative for virus by PCR.
PMID- 29350170
TI - Atypical lower motor neuron disease with enlargement of Nissl substance: Report
of an autopsy case.
AB - The patient was an 81-year-old woman diagnosed with atypical motor neuron disease
who died after a long clinical course (7.5 years without mechanical assistance of
ventilation) characterized by lower motor neuron signs and symptoms. Upper motor
neuron signs and cognitive impairment were not apparent. Autopsy demonstrated
severe neuronal loss in the anterior horn of the spinal cord, and some of the
remaining neurons showed enlargement of Nissl substance and apparent thickening
of the nuclear envelopes. No Bunina bodies, skein-like inclusions, or structures
immunoreactive for phosphorylated transactivation response DNA-binding protein 43
were found. Immunoreactivity for superoxide dismutase-1 was focally seen in the
enlarged Nissl substance. Ultrastructural examination demonstrated an increase of
rough-surfaced endoplasmic reticulum (rough ER) and free ribosomes,
disaggregation of polyribosomes, and dispersion of free ribosomes. Cisterns of
rough ER were slightly dilated, and some of them were closely attached to the
nuclear envelopes. Enlargement of Nissl substance may be related to "ER stress",
and the abnormal findings of rough ER and free ribosomes may represent a
degenerative process. However, another possibility, that they represent a
compensatory hyperplastic change, cannot be excluded. The close attachment of
cisterns of rough ER to the nuclear envelopes may be a mechanism to support or
compensate for the abnormally-fragile nuclear envelopes.?.
PMID- 29350171
TI - The DNA copy number landscape of a collision tumor.
AB - Intracranial collision tumors are composed of two histologically distinct but
merging components, and are rare. Their genetic profile has rarely been
described. Comparative genome hybridization of a combined meningioma and
oligodendroglioma demonstrated deletion of chromosome 22q and of 19q in both
tumors. Somatic deletion of chromosome 22q and 19q is associated with development
of an intracranial collision tumor.?.
PMID- 29350172
TI - Comparison of dialysate and plasma NTproBNP in prediction of clinical outcomes of
diabetic and nondiabetic peritoneal dialysis patients?.
AB - BACKGROUND: Plasma level of N-terminal pro-brain natriuretic peptide (P-NTproBNP)
is a useful marker in prediction of mortality in peritoneal dialysis (PD)
patients. However, the predictive value of spent dialysate counterpart (D
NTproBNP) of plasma NTproBNP on mortality and dropout is not known. MATERIALS AND
METHODS: Simultaneous P-NTproBNP and D-NTproBNP assays were performed after an
overnight dwell in 44 scheduled ambulatory PD patients. Patients were followed
for ~ 47 months. Deceased patients or patients who were transferred to
hemodialysis were regarded as dropouts. RESULTS: 14 patients (31.8%) dropped out
at ~ 4 years (9 deaths and 5 transfers to hemodialysis). Diabetics, males, and
patients with higher membrane permeability had higher dropout rates. Patients
with P- and D-NTproBNP higher than median values had higher mortality and dropout
rates (Kaplan-Meier test, log-rank Test p < 0.05). Odds ratios of D-NTproBNP for
death and dropouts were (3.807 (0.907 - 15.971), p = 0.068) and (2.87 (1.009 -
8.138) p = 0.048), respectively; odds ratios of P-NTproBNP for death and dropouts
were (4.652 (0.914 - 23.693), p = 0.064) and (2.67 (0.924 - 7.716), p = 0.07),
respectively; in ROC analysis for death, AUC for P- and D-NTproBNP were 0.762
(0.578 - 0.946, p = 0.016) and 0.765 (0.590 - 0.940, p = 0.015), respectively.
Exclusion of diabetic patients from the analyses resulted in significant changes
in the predictive value P- and D-NTproBNP. Although death and dropout rates were
still higher in nondiabetic patients with higher NTproBNP levels, the differences
between groups lost statistical significance. CONCLUSIONS: Both P-NTproBNP and D
NTproBNP are significant predictors of outcomes of interest. Predictive value of
NTproBNP might be different in diabetics and non-diabetic CAPD patients.?.
PMID- 29350173
TI - Membranoproliferative glomerulonephritis and interstitial nephritis in the
setting of Epstein-Barr virus-related hemophagocytic syndrome?.
AB - BACKGROUND: Hemophagocytic syndrome (HPS) is a rare, aggressive disorder
characterized by dysregulation of lymphocyte and macrophage activity, which
culminates in tissue infiltration with hemophagocytosis and ultimately organ
failure. Renal involvement frequently ensues and usually results in acute tubular
necrosis with associated interstitial inflammation. Less frequently,
glomerulopathy can also be found. CASE: We report a case of a 24-year-old
Caucasian woman with previous asymptomatic hematuria, mild proteinuria, and
normal renal function who presented to us with fever. Laboratory findings
revealed pancytopenia, elevated lactate dehydrogenase, and ferritin as well as
liver and kidney failure. Renal biopsy showed a tubulointerstitial nephritis
superimposed in a membranoproliferative glomerulonephritis with crescents.
Extensive etiologic investigation was negative except for Epstein-Barr virus
(EBV) viral load. EBV-DNA was then identified by in situ hybridization in the
renal biopsy. HPS could be diagnosed with the presence of six criteria: fever,
splenomegaly, bicytopenia, high ferritin, hypertriglyceridemia, and high levels
of soluble CD25. Steroid therapy was initiated with resolution of HPS as well as
complete recovery of renal and liver function. CONCLUSION: In this case, we
believe that EBV triggered both HPS and tubulointerstitial nephritis. Steroid
therapy successfully treated the inflammatory syndrome, allowing renal function
recovery without compromising EBV infection resolution.?.
PMID- 29350174
TI - Automated peritoneal dialysis could rapidly improve left heart failure by
increasing peritoneal dialysis ultrafiltration: a single-center observational
clinical study?.
AB - Ultrafiltration failure (UFF) is a major cause of water retention, left heart
failure (LHF), and peritoneal dialysis (PD) failure. Automated peritoneal
dialysis (APD) might have better ultrafiltration (UF) than continuous ambulatory
peritoneal dialysis (CAPD). Here, we have studied whether short-term APD could
increase UF and improve LHF. 47 patients were included in this study from
December 1, 2015, to January 1, 2017. All patients had been treated with CAPD
before they came to our center and were treated with APD in the hospital. 24-hour
peritoneal UF volume, 24-hour urine volume, body weight, blood pressure, LHF
class, serum creatinine, blood urea nitrogen, albumin, potassium, hemoglobin, and
glucose were collected and compared before and after receiving short-time APD. A
total of 47 patients (31 men, mean age 46.8 +/- 16.2 years, mean duration 26
months (2 - 195 months)) were enrolled in this study. Of the 47 patients,
peritoneal dialysis UF was significantly increased when receiving short-term APD
compared to CAPD (1,261.9 +/- 329.6 mL vs. 706.2 +/- 222.3 mL, p < 0.001), and
body weights had significantly decreased 3 days after treatment with APD (57.73
+/- 10.5 vs. 59.81 +/- 10.8, p < 0.001). LHF class was significantly decreased 3
days after receiving APD (1.7 +/- 0.8 vs. 2.4 +/- 1.0, p < 0.001). Blood pressure
was well controlled 3 days after treatment with APD (146.6 +/- 14.4 vs. 162.5 +/-
23.8 of SBP, p = 0.007, and 85.6 +/- 11.1 vs. 95.6 +/- 14.7 of DBP, p = 0.001).
In conclusion, short-term APD could significantly increase ultrafiltration,
rapidly alleviate edema and improve LHF, and might be an effective method to
treat UFF and LHF in PD patients.?.
PMID- 29350175
TI - Update on the nephrotoxicity of novel anticancer agents?.
AB - Anticancer drug-induced kidney disease is a problem commonly encountered by
nephrologists. The number of medications employed by oncologists causing acute
and chronic kidney injury as well as electrolyte and acid-base disturbances has
increased significantly over the past several decades. While conventional
chemotherapeutic drugs induce a number of kidney lesions, emergence of very
effective and well-tolerated targeted therapies and novel immunotherapies has
increased the occurrence of drug-induced acute and chronic kidney injury in
cancer patients. This article will review the various kidney lesions observed
with these new classes of anticancer drugs.?.
PMID- 29350176
TI - Pharmacokinetic characterization of three novel 4-mg nicotine lozenges?.
AB - OBJECTIVE: Nicotine replacement therapy (NRT) increases the probability of
smoking cessation. This study was conducted to determine if three prototype 4-mg
nicotine lozenges produced locally in India were bioequivalent to a globally
marketed reference product, Nicorette(r) 4-mg nicotine lozenge. MATERIALS AND
METHODS: Healthy adult smokers (N = 39) were treated with three prototype 4-mg
nicotine lozenges in comparison with a reference 4-mg lozenge in this single
center, randomized, open-label, single-dose, 4-way crossover study.
Pharmacokinetic sampling was obtained to test for bioequivalence using maximal
plasma concentration (Cmax) and extent of absorption (AUC0-t). Secondarily, AUC;0
infinity, time to maximal plasma concentration (tmax), half-life (T1/2),
elimination rate constant (Kel), and safety of the prototype lozenges versus the
reference lozenge were compared. RESULTS: Each prototype 4-mg nicotine lozenge
was found to be bioequivalent to the reference 4-mg nicotine lozenge based on the
ratio of geometric means and 90% confidence intervals for Cmax, AUC0-t, and AUC;0
infinity. Although tmax; was significantly longer for prototype III, all four
lozenges achieved maximum plasma nicotine concentrations at a median of 1.5
hours. The safety profiles of the three prototype 4-mg lozenges did not differ
from that of the 4-mg reference product. CONCLUSION: Each prototype 4-mg nicotine
lozenge was bioequivalent to the reference 4-mg nicotine lozenge and was well
tolerated. Furthermore, as these bioequivalent prototypes differed in in-vitro
dissolution profiles, these data suggest that performance from the in -vitro
method deployed is not a firm predictor of pharmacokinetic behavior.?.
PMID- 29350177
TI - Antidepressant medication in a German cohort of patients with Alzheimer's
disease?.
AB - OBJECTIVE: The use of antidepressant drugs in dementia patients is associated
with the risk of adverse events, and the evidence for relevant effects is scarce.
We aimed to determine the associations between the prescription of
antidepressants and patients' sociodemographic (e.g., age, gender, living
situation) and clinical characteristics (e.g., disease severity, neuropsychiatric
symptoms). MATERIALS AND METHODS: We included 395 institutionalized and community
dwelling patients with Alzheimer's disease (AD) across all severity stages of
dementia in a cross-sectional study design. The patients' clinical
characteristics comprised of cognitive status, daily activities, depressive
symptoms, further neuropsychiatric symptoms, and health-related quality of life
(HrQoL). We conducted multiple logistic regression analyses for the association
between the use of antidepressant drugs and the covariates. RESULTS:
Approximately 31% of the participants were treated with antidepressant drugs,
with a higher chance of being medicated for institutionalized patients (chi2
test: p = 0.010). In the bivariate analyses, the use of antidepressants was
significantly associated with higher levels of care, lower cognitive and daily
life capacity, higher extent of neuropsychiatric symptoms, and a lower proxy
reported HrQoL. Finally, multiple logistic regression models showed a
significantly higher use of antidepressants in patients treated by psychiatrists
and neurologists (OR 2.852, 95% CI: 1.223 - 6.652). CONCLUSION: The use of
antidepressant drugs in the study population was high, and the suitability of the
treatment with antidepressants remains unclear. Participants with diminished
cognitive and functional capacity, higher extent of neuropsychiatric symptoms,
and those treated by neuropsychiatric specialists were more likely to be treated
with antidepressants. The pharmaceutical treatment of patients with these
clinical characteristics should be particularly considered in the daily care for
dementia patients. Further longitudinal studies should evaluate the
appropriateness of indications for antidepressants and the causative direction of
correlations with the patients' clinical characteristics.?.
PMID- 29350178
TI - Use of rifabutin to treat tuberculosis in a cardiac transplant recipient: A case
report?.
AB - OBJECTIVE: Tuberculosis is an important concern following organ transplantation.
Unfortunately, several antituberculosis drugs interact with immunosuppressants.
This report describes our experience with rifabutin (RBT) in the treatment of
acute tuberculosis in a cardiac transplant recipient. CASE: A 61-year-old cardiac
transplant recipient developed tuberculosis meningitis during treatment of
miliary tuberculosis. RBT was given for 27 days concomitantly with cyclosporine
(CsA). CsA concentrations at 0 hour (C0) decreased within 3 days of
starting RBT. The serum concentration-curve from 0 to 12 hours (AUC0
12h)/dose 7 days after starting RBT therapy decreased by 28%, compared to
the values before RBT therapy. The apparent clearance at both 7 and 21 days after
starting RBT therapy was 1.4 times higher than before RBT therapy. CONCLUSION:
RBT has fewer drug-drug interactions than rifampin and should be preferentially
used for the treatment of tuberculosis in transplant patients treated with CsA.
Close monitoring of CsA blood concentration during RBT therapy minimized the risk
of under- or over-immunosuppression in a cardiac transplant patient.?.
PMID- 29350179
TI - Risks in the clinical applications of scopolamine butylbromide injections.
AB - OBJECTIVE: To investigate and analyze the clinical application of scopolamine
butylbromide injection and promote the rational use of the drug. MATERIALS AND
METHODS: We classified and analyzed 3,695 cases of scopolamine butylbromide
injection (effective cases only) collected over the period of January 2016 to
July 2017, including details on gender, age, course of treatment, high-risk
patients with other medications, adverse drug reactions, and drug combinations.
RESULTS: Use in high-risk patients is common, occurrence of adverse drug reaction
rate in patients with high risk is 8.32 times the incidence of adverse reactions
of the drug in general, in high-risk patients with adverse drug reaction the rate
is 7.63 times that for lower-risk patients. Combined use of drugs is common, and
there are 1.98% of cases with potential drug interactions. CONCLUSION: The
findings have importance for other Asian ethnic groups and for Chinese living
outside China - Chinese are considered a "moderate-risk" ethnic group in using
scopolamine butylbromide injection. We should adhere to the requirements of drug
instructions, pay attention to high-risk patients, drug and drug interactions,
drug and food interactions, reduce the risk of adverse drug reactions, and ensure
drug safety.
PMID- 29350180
TI - Genetic characterization of three mitochondrial gene sequences of goat/sheep
derived coenurus cerebralis and cysticercus tenuicollis isolates in Inner
Mongolia, China.
AB - Taenia multiceps and Taenia hydatigena are widely distributed tapeworms of
canids. Due to a lack of genetic information on these two parasites in China, in
this study we analyzed six coenurus cerebralis and two cysticercus tenuicollis
cysts from goats or sheep in Inner Mongolia, northern China by amplifying three
mitochondrial genes (cox1, nad4, and cytb). Two haplotypes were obtained at each
locus for either of the two Taenia cestode species, with ten nucleotide sequences
being novel. The degrees of genetic variations were 1.18%, 0.61% and 0.52% for
coenurus cerebralis, and 0.24%, 0.46% and 0.35% for cysticercus tenuicollis at
the cox1, nad4 and cytb loci, respectively. This is the first molecular
description of animal-derived metacestodes of T. multiceps and T. hydatigena in
Inner Mongolia, China. Novel nucleotide sequences might reflect endemic genetic
characterization of the two cestodes. The present data are useful to explore the
biological and epidemiological significance of intra-specific variations within
both Taenia cestodes.
PMID- 29350181
TI - A single, continuous metric to define tiered serum neutralization potency against
HIV.
AB - HIV-1 Envelope (Env) variants are grouped into tiers by their neutralization
sensitivity phenotype. This helped to recognize that tier 1 neutralization
responses can be elicited readily, but do not protect against new infections.
Tier 3 viruses are the least sensitive to neutralization. Because most
circulating viruses are tier 2, vaccines that elicit neutralization responses
against them are needed. While tier classification is widely used for viruses, a
way to rate serum or antibody neutralization responses in comparable terms is
needed. Logistic regression of neutralization outcomes summarizes serum or
antibody potency on a continuous, tier-like scale. It also tests significance of
the neutralization score, to indicate cases where serum response does not depend
on virus tiers. The method can standardize results from different virus panels,
and could lead to high-throughput assays, which evaluate a single serum dilution,
rather than a dilution series, for more efficient use of limited resources to
screen samples from vaccinees.
PMID- 29350182
TI - The role of EEG in the diagnosis and classification of the epilepsy syndromes: a
tool for clinical practice by the ILAE Neurophysiology Task Force (Part 2).
AB - The concept of epilepsy syndromes, introduced in 1989, was defined as "clusters
of signs and symptoms customarily occurring together". Definition of epilepsy
syndromes based on electro-clinical features facilitated clinical practice and,
whenever possible, clinical research in homogeneous groups of patients with
epilepsies. Progress in the fields of neuroimaging and genetics made it rapidly
clear that, although crucial, the electro-clinical description of epilepsy
syndromes was not sufficient to allow much needed development of targeted
therapies and a better understanding of the underlying pathophysiological
mechanisms of seizures. The 2017 ILAE position paper on Classification of the
Epilepsies recognized that "as a critical tool for the practicing clinician,
epilepsy classification must be relevant and dynamic to changes in thinking". The
concept of "epilepsy syndromes" evolved, incorporating issues related to
aetiologies and comorbidities. A comprehensive update (and revision where
necessary) of the EEG diagnostic criteria in the light of the 2017 revised
terminology and concepts was deemed necessary. Part 2 covers the neonatal and
paediatric syndromes in accordance with the age of onset. [Published with
educational EEG plates at www.epilepticdisorders.com].
PMID- 29350183
TI - Integrated biocircuits: engineering functional multicellular circuits and
devices.
AB - OBJECTIVE: Implantable neurotechnologies have revolutionized neuromodulatory
medicine for treating the dysfunction of diseased neural circuitry. However,
challenges with biocompatibility and lack of full control over neural network
communication and function limits the potential to create more stable and robust
neuromodulation devices. Thus, we propose a platform technology of implantable
and programmable cellular systems, namely Integrated Biocircuits, which use only
cells as the functional components of the device. APPROACH: We envision the
foundational principles for this concept begins with novel in vitro platforms
used for the study and reconstruction of cellular circuitry. Additionally, recent
advancements in organoid and 3D culture systems account for microenvironment
factors of cytoarchitecture to construct multicellular circuits as they are
normally formed in the brain. We explore the current state of the art of these
platforms to provide knowledge of their advancements in circuit fabrication and
identify the current biological principles that could be applied in designing
integrated biocircuit devices. MAIN RESULTS: We have highlighted the exemplary
methodologies and techniques of in vitro circuit fabrication and propose the
integration of selected controllable parameters, which would be required in
creating suitable biodevices. SIGNIFICANCE: We provide our perspective and
propose new insights into the future of neuromodulaion devices within the scope
of living cellular systems that can be applied in designing more reliable and
biocompatible stimulation-based neuroprosthetics.
PMID- 29350184
TI - Chirality in molecular collision dynamics.
AB - Chirality is a phenomenon that permeates the natural world, with implications for
atomic and molecular physics, for fundamental forces and for the mechanisms at
the origin of the early evolution of life and biomolecular homochirality. The
manifestations of chirality in chemistry and biochemistry are numerous, the
striking ones being chiral recognition and asymmetric synthesis with important
applications in molecular sciences and in industrial and pharmaceutical
chemistry. Chiral discrimination phenomena, due to the existence of two
enantiomeric forms, very well known in the case of interaction with light, but
still nearly disregarded in molecular collision studies. Here we review some
ideas and recent advances about the role of chirality in molecular collisions,
designing and illustrating molecular beam experiments for the demonstration of
chiral effects and suggesting a scenario for a stereo-directional origin of
chiral selection.
PMID- 29350185
TI - Fluorescence detection of glutathione and oxidized glutathione in blood with a
NIR-excitable cyanine probe.
AB - Cyanine has been widely utilized as a near infrared (NIR) fluorophore for
detection of glutathione (GSH). However, the excitation of most of the reported
cyanine-based probes was less than 800 nm, which inevitably induce biological
background absorption and lower the sensitivity, limiting their use for detection
of GSH in blood samples. To address this issue, here, a heptamethine cyanine
probe (DNIR), with a NIR excitation wavelength at 804 nm and a NIR emission
wavelength at 832 nm, is employed for the detection of GSH and its oxidized form
(GSSG) in blood. The probe displays excellent selectivity for GSH over GSSG and
other amino acids, and rapid response to GSH, in particular a good property for
indirect detection of GSSG in the presence of enzyme glutathione reductase and
the reducing agent nicotinamideadenine dinucleotide phosphate, without further
separation prior to fluorescent measurement. To the best of our knowledge, this
is the first attempt to explore NIR fluorescent approach for the simultaneous
assay of GSH and GSSG in blood. As such, we expect that our fluorescence sensors
with both NIR excitation and NIR emission make this strategy suitable for the
application in complex physiological systems.
PMID- 29350186
TI - MRI tracing non-invasive TiO2-based nanoparticles activated by ultrasound for
multi-mechanism therapy of prostatic cancer.
AB - To reduce the side effects of chemotherapy and achieve effective and safe therapy
for prostate cancer, herein a simple but multi-functional TiO2:Gd@DOX/FA system
activated by ultrasound was developed for the MRI-guided multi-mechanism therapy
of prostate cancer. TiO2 nanoparticles served as a sonosensitizer as well as a
nanocarrier with the pH-responsive release of DOX. The doping of Gd was not only
able to endow the TiO2 with magnetic resonance imaging (MRI) ability, but also
further improve the sonodynamic ability of the TiO2. The characterization of the
as-prepared TiO2:Gd@DOX/FA showed sensitive pH-responsive drug release, high
reactive oxygen species (ROS) production, T 1-MRI contrast performance and
excellent biocompatibility. The cytotoxicity assay in vitro showed cell death up
to 91.68% after 48 h incubation induced by the TiO2:Gd@DOX + ultrasound group.
Meanwhile, in the in vivo synergistic therapy studies, the tumor sizes of all the
nanomedicine groups were smaller than for the free DOX (V:V 0 = 4.2). More
importantly, the body showed nearly no weight loss. This safety was also
confirmed by the H&E staining, biodistribution experiment and serum biochemistry
results. Altogether, TiO2:Gd@DOX/FA significantly reduced the side effects of
DOX, augmented the levels of ROS and achieved effective and safe therapy,
indicating its potential for the multi-mechanism therapy of prostate cancer.
PMID- 29350187
TI - Multifractal dynamics of resting-state functional connectivity in the prefrontal
cortex.
AB - : Brain function is organized as a network of functional connections between
different neuronal populations with connection strengths dynamically changing in
time and space. Studies investigating functional connectivity (FC) usually follow
a static approach when describing FC by considering the connectivity strengths
constant, however a dynamic approach seems more reasonable, as this way the
spatio-temporal dynamics of the underlying system can also be captured.
OBJECTIVE: The scale-free, i.e. fractal nature of neural dynamics is an inherent
property of the nervous system. The aim of this study was to determine if dynamic
functional connectivity (DFC) in the prefrontal cortex shows not only scale-free
but indeed multifractal dynamics. APPROACH: Functional near-infrared spectroscopy
(fNIRS) was used to monitor resting-state brain activity in young healthy
volunteers. Sliding window correlation (SWC) analysis and graph theory approach
were utilized to capture the functional connection networks for every time point,
whose topology was subsequently characterized with three network metrics-Density,
Clustering Coefficient and Efficiency-each capturing a different aspect of the
given network. The temporal structuring of the obtained network metric time
series was then described by multifractal time series analysis. MAIN RESULTS: We
found the DFC in the prefrontal cortex fluctuating according to scale-free,
specifically multifractal dynamics. Moreover, different topological properties of
the network showed different multifractal characteristics. All the results were
reproducible in all window sizes used in the SWC analysis, however we found that
the actual values of the given multifractal properties depended significantly on
the window size. SIGNIFICANCE: Our results may well be another indication of a
self-organized critical state underlying resting-state brain activity. The
proposed analysis of functional brain dynamics can also open new perspectives for
future clinical applications.
PMID- 29350188
TI - Accurate identification of layer number for few-layer WS2 and WSe2 via
spectroscopic study.
AB - Transition metal dichalcogenides (TMDs) with a typical layered structure are
highly sensitive to their layer number in optical and electronic properties.
Seeking a simple and effective method for layer number identification is very
important to low-dimensional TMD samples. Herein, a rapid and accurate layer
number identification of few-layer WS2 and WSe2 is proposed via locking their
photoluminescence (PL) peak-positions. As the layer number of WS2/WSe2 increases,
it is found that indirect transition emission is more thickness-sensitive than
direct transition emission, and the PL peak-position differences between the
indirect and direct transitions can be regarded as fingerprints to identify their
layer number. Theoretical calculation confirms that the notable thickness
sensitivity of indirect transition derives from the variations of electron
density of states of W atom d-orbitals and chalcogen atom p-orbitals. Besides,
the PL peak-position differences between the indirect and direct transitions are
almost independent of different insulating substrates. This work not only
proposes a new method for layer number identification via PL studies, but also
provides a valuable insight into the thickness-dependent optical and electronic
properties of W-based TMDs.
PMID- 29350189
TI - Detection of thoracic vascular structures by electrical impedance tomography: a
systematic assessment of prominence peak analysis of impedance changes.
AB - OBJECTIVE: Electrical impedance tomography (EIT) is a non-invasive and radiation
free bedside monitoring technology, primarily used to monitor lung function.
First experimental data shows that the descending aorta can be detected at
different thoracic heights and might allow the assessment of central
hemodynamics, i.e. stroke volume and pulse transit time. APPROACH: First, the
feasibility of localizing small non-conductive objects within a saline phantom
model was evaluated. Second, this result was utilized for the detection of the
aorta by EIT in ten anesthetized pigs with comparison to thoracic computer
tomography (CT). Two EIT belts were placed at different thoracic positions and a
bolus of hypertonic saline (10 ml, 20%) was administered into the ascending aorta
while EIT data were recorded. EIT images were reconstructed using the GREIT
model, based on the individual's thoracic contours. The resulting EIT images were
analyzed pixel by pixel to identify the aortic pixel, in which the bolus caused
the highest transient impedance peak in time. MAIN RESULTS: In the phantom, small
objects could be located at each position with a maximal deviation of 0.71 cm. In
vivo, no significant differences between the aorta position measured by EIT and
the anatomical aorta location were obtained for both measurement planes if the
search was restricted to the dorsal thoracic region of interest (ROIs).
SIGNIFICANCE: It is possible to detect the descending aorta at different thoracic
levels by EIT using an intra-aortic bolus of hypertonic saline. No significant
differences in the position of the descending aorta on EIT images compared to CT
images were obtained for both EIT belts.
PMID- 29350190
TI - Development and validation of a high-resolution mapping platform to aid in the
public awareness of radiological hazards.
AB - The distribution, quantification and exposure-related effects of radiation in the
environment, arising from both natural and anthropogenic sources, is of great
(and growing) concern for global populations. Recent events at the Fukushima
Daiichi Nuclear Plant (FDNPP) have further highlighted the importance of
developing radiation mapping technologies that not only contribute to the
continued assessment of contamination, but can serve as an educational tool for
members of the public regarding both its behaviour and extent. With an even
greater number of people possessing smart-phone technology, a lightweight and
portable 'connected system' has been developed to demonstrate to users the
calibrated radioactive dose rate in an area, viewable in real-time through a
dedicated phone application. As well as allowing for system users to be alerted
where variations in dose rate are experienced, the combined results from multiple
systems are viewable through a custom-built desktop application-permitting the
output obtained via any number of units to be similarly displayed in real-time. A
successful initial trialling of the system is described at a former tin mine in
Cornwall (south-west England)-known to exhibit low, but identifiable radiation
anomalies in discrete areas. Additional applications outside of its educational
usage are also discussed.
PMID- 29350191
TI - A prospective gating method to acquire a diverse set of free-breathing CT images
for model-based 4DCT.
AB - Breathing motion modeling requires observation of tissues at sufficiently
distinct respiratory states for proper 4D characterization. This work proposes a
method to improve sampling of the breathing cycle with limited imaging dose. We
designed and tested a prospective free-breathing acquisition protocol with a
simulation using datasets from five patients imaged with a model-based 4DCT
technique. Each dataset contained 25 free-breathing fast helical CT scans with
simultaneous breathing surrogate measurements. Tissue displacements were measured
using deformable image registration. A correspondence model related tissue
displacement to the surrogate. Model residual was computed by comparing predicted
displacements to image registration results. To determine a stopping criteria for
the prospective protocol, i.e. when the breathing cycle had been sufficiently
sampled, subsets of N scans where 5 ? N ? 9 were used to fit reduced models
for each patient. A previously published metric was employed to describe the
phase coverage, or 'spread', of the respiratory trajectories of each subset.
Minimum phase coverage necessary to achieve mean model residual within 0.5 mm of
the full 25-scan model was determined and used as the stopping criteria. Using
the patient breathing traces, a prospective acquisition protocol was simulated.
In all patients, phase coverage greater than the threshold necessary for model
accuracy within 0.5 mm of the 25 scan model was achieved in six or fewer scans.
The prospectively selected respiratory trajectories ranked in the (97.5 +/-
4.2)th percentile among subsets of the originally sampled scans on average.
Simulation results suggest that the proposed prospective method provides an
effective means to sample the breathing cycle with limited free-breathing scans.
One application of the method is to reduce the imaging dose of a previously
published model-based 4DCT protocol to 25% of its original value while achieving
mean model residual within 0.5 mm.
PMID- 29350192
TI - Size-dependent Young's modulus in ZnO nanowires with strong surface atomic bonds.
AB - The mechanical properties of size-dependent nanowires are important in nano
electro-mechanical systems (NEMSs), and have attracted much research interest.
Characterization of the size effect of nanowires in atmosphere directly to
broaden their practical application instead of just in high vacuum situations, as
reported previously, is desperately needed. In this study, we systematically
studied the Young's modulus of vertical ZnO nanowires in atmosphere. The
diameters ranged from 48 nm to 239 nm with a resonance method using non-contact
atomic force microscopy. The values of Young's modulus in atmosphere present
extremely strong increasing tendency with decreasing diameter of nanowire due to
stronger surface atomic bonds compared with that in vacuum. A core-shell model
for nanowires is proposed to explore the Young's modulus enhancement in
atmosphere, which is correlated with atoms of oxygen occurring near the nanowire
surface. The modified model is more accurate for analyzing the mechanical
behavior of nanowires in atmosphere compared with the model in vacuum.
Furthermore, it is possible to use this characterization method to measure the
size-related elastic properties of similar wire-sharp nanomaterials in atmosphere
and estimate the corresponding mechanical behavior. The study of the size
dependent Young's modulus in ZnO nanowires in atmosphere will improve the
understanding of the mechanical properties of nanomaterials as well as providing
guidance for applications in NEMSs, nanogenerators, biosensors and other related
areas.
PMID- 29350193
TI - Layer structured bismuth selenides Bi2Se3 and Bi3Se4 for high energy and flexible
all-solid-state micro-supercapacitors.
AB - In this work, bismuth selenides (Bi2Se3 and Bi3Se4), both of which have a layered
rhombohedral crystal structure, have been found to be useful as electrode
materials for supercapacitor applications. In a liquid electrolyte system (6M
KOH), Bi2Se3 nanoplates exhibit much better performance as an electrode material
than Bi3Se4 nanoparticles do, delivering a higher specific capacitance (272.9 F g
1) than that of Bi3Se4 (193.6 F g-1) at 5 mV s-1. This result may be attributed
to the fact that Bi2Se3 nanoplates possess more active electrochemical surfaces
for the reversible surface redox reactions owing to their planar quintuple
stacked layers (septuple layers for Bi3Se4). To meet the demands of electronic
skin, we used a novel flexible annular interdigital structure electrode to
support the all-solid-state micro-supercapacitors (AMSCs). The Bi2Se3 AMSC device
delivers a much better supercapacitor performance, exhibits a large stack
capacitance of 89.5 F cm-3 at 20 mV s-1 (Bi3Se4: 79.1 F cm-3), a high energy
density of 17.9 mWh cm-3 and a high power density of 18.9 W cm-3. The bismuth
selenides also exhibit good cycle stability, with 95.5% retention after 1000 c
for Bi2Se3 (Bi3Se4:90.3%). Clearly, Bi2Se3 nanoplates can be promising electrode
materials for flexible annular interdigital AMSCs.
PMID- 29350194
TI - Detection rate of fetal distress using contraction-dependent fetal heart rate
variability analysis.
AB - OBJECTIVE: Monitoring of the fetal condition during labor is currently performed
by cardiotocograpy (CTG). Despite the use of CTG in clinical practice, CTG
interpretation suffers from a high inter- and intra-observer variability and a
low specificity. In addition to CTG, analysis of fetal heart rate variability
(HRV) has been shown to provide information on fetal distress. However, fetal HRV
can be strongly influenced by uterine contractions, particularly during the
second stage of labor. Therefore, the aim of this study is to examine if
distinguishing contractions from rest periods can improve the detection rate of
HRV features for fetal distress during the second stage of labor. APPROACH: We
used a dataset of 100 recordings, containing 20 cases of fetuses with adverse
outcome. The most informative HRV features were selected by a genetic algorithm
and classification performance was evaluated using support vector machines. MAIN
RESULTS: Classification performance of fetal heart rate segments closest to birth
improved from a geometric mean of 70% to 79%. If the classifier was used to
indicate fetal distress over time, the geometric mean at 15 minutes before birth
improved from 60% to 72%. SIGNIFICANCE: Our results show that combining
contraction-dependent HRV features with HRV features calculated over the entire
fetal heart rate signal improves the detection rate of fetal distress.
PMID- 29350195
TI - Design and fabrication of a multifocal bionic compound eye for imaging.
AB - Miniaturized bionic compound eyes featured with multi-aperture imaging have
potential applications in the areas of micro opto-electro-mechanical-system. In
this manuscript, we present a novel structure of the bionic compound eye with
multiple focal lengths consists of an array of individual lenses with 1000 um
diameter. The simulation results of the designed multifocal bionic compound eye
(MBCE) with two focal lengths of 190 mm and 44.4 mm demonstrate excellent two
order focusing abilities. Moving mask exposure technology was used to fabricate
the designed MBCE with the corresponding imaging experiments conducted to
validate the two-order imaging ability of the fabricated MBCE. Experimental
results revealed that the developed structure has potential applications in
diverse optical imaging systems such as three-dimensional imaging and real-time
detection of unconfined or fluctuating targets.
PMID- 29350196
TI - Estimation and correction of produced light from prompt gamma photons on
luminescence imaging of water for proton therapy dosimetry.
AB - Although the luminescence images of water during proton-beam irradiation using a
cooled charge-coupled device camera showed almost the same ranges of proton beams
as those measured by an ionization chamber, the depth profiles showed lower Bragg
peak intensities than those measured by an ionization chamber. In addition, a
broad optical baseline signal was observed in depths that exceed the depth of the
Bragg peak. We hypothesize that this broad baseline signal originates from the
interaction of proton-induced prompt gamma photons with water. These prompt gamma
photons interact with water to form high-energy Compton electrons, which may
cause luminescence or Cherenkov emission from depths exceeding the location of
the Bragg peak. To clarify this idea, we measured the luminescence images of
water during the irradiations of protons in water with minimized parallax errors,
and also simulated the produced light by the interactions of prompt gamma photons
with water. We corrected the measured depth profiles of the luminescence images
by subtracting the simulated distributions of the produced light by the
interactions of prompt gamma photons in water. Corrections were also conducted
using the estimated depth profiles of the light of the prompt gamma photons, as
obtained from the off-beam areas of the luminescence images of water. With these
corrections, we successfully obtained depth profiles that have almost identical
distributions as the simulated dose distributions for protons. The percentage
relative height of the Bragg peak with corrections to that of the simulation data
increased to 94% from 80% without correction. Also, the percentage relative
offset heights of the deeper part of the Bragg peak with corrections decreased to
0.2%-0.4% from 4% without correction. These results indicate that the
luminescence imaging of water has potential for the dose distribution
measurements for proton therapy dosimetry.
PMID- 29350197
TI - A 3D correction method for predicting the readings of a PinPoint chamber on the
CyberKnife(r) M6TM machine.
AB - The use of small fields in radiation therapy techniques has increased
substantially in particular in stereotactic radiosurgery (SRS) and stereotactic
body radiation therapy (SBRT). However, as field size reduces further still, the
response of the detector changes more rapidly with field size, and the effects of
measurement uncertainties become increasingly significant due to the lack of
lateral charged particle equilibrium, spectral changes as a function of field
size, detector choice, and subsequent perturbations of the charged particle
fluence. This work presents a novel 3D dose volume-to-point correction method to
predict the readings of a 0.015 cc PinPoint chamber (PTW 31014) for both small
static-fields and composite-field dosimetry formed by fixed cones on the
CyberKnife(r) M6TM machine. A 3D correction matrix is introduced to link the 3D
dose distribution to the response of the PinPoint chamber in water. The
parameters of the correction matrix are determined by modeling its 3D dose
response in circular fields created using the 12 fixed cones (5 mm-60 mm) on a
CyberKnife(r) M6TM machine. A penalized least-square optimization problem is
defined by fitting the calculated detector reading to the experimental
measurement data to generate the optimal correction matrix; the simulated
annealing algorithm is used to solve the inverse optimization problem. All the
experimental measurements are acquired for every 2 mm chamber shift in the
horizontal planes for each field size. The 3D dose distributions for the
measurements are calculated using the Monte Carlo calculation with the
MultiPlan(r) treatment planning system (Accuray Inc., Sunnyvale, CA, USA). The
performance evaluation of the 3D conversion matrix is carried out by comparing
the predictions of the output factors (OFs), off-axis ratios (OARs) and
percentage depth dose (PDD) data to the experimental measurement data. The
discrepancy of the measurement and the prediction data for composite fields is
also performed for clinical SRS plans. The optimization algorithm used for
generating the optimal correction factors is stable, and the resulting correction
factors were smooth in the spatial domain. The measurement and prediction of OFs
agree closely with percentage differences of less than 1.9% for all the 12 cones.
The discrepancies between the prediction and the measurement PDD readings at 50
mm and 80 mm depth are 1.7% and 1.9%, respectively. The percentage differences of
OARs between measurement and prediction data are less than 2% in the low dose
gradient region, and 2%/1 mm discrepancies are observed within the high dose
gradient regions. The differences between the measurement and prediction data for
all the CyberKnife based SRS plans are less than 1%. These results demonstrate
the existence and efficiency of the novel 3D correction method for small field
dosimetry. The 3D correction matrix links the 3D dose distribution and the
reading of the PinPoint chamber. The comparison between the predicted reading and
the measurement data for static small fields (OFs, OARs and PDDs) yield
discrepancies within 2% for low dose gradient regions and 2%/1 mm for high dose
gradient regions; the discrepancies between the predicted and the measurement
data are less than 1% for all the SRS plans. The 3D correction method provides an
access to evaluate the clinical measurement data and can be applied to non
standard composite fields intensity modulated radiation therapy point dose
verification.
PMID- 29350198
TI - Preparation of sub 3 nm copper nanoparticles by microwave irradiation in the
presence of triethylene tetramin.
AB - The preparation of sub 3 nm copper nanoparticles (CuNPs) in ethylene glycol (EG)
using triethylene tetramine (TETA) as chelating and reducing agents via a rapid
microwave (MW) irradiation is reported. The sub 3 nm CuNPs after MW irradiation
are clearly seen from the electronic micrographs. The firm chelation of Cu2+ by
TETA is illustrated by the dark blue color of Cu2+/TETA/EG solution and the redox
reaction is confirmed by the appearance of red color of the mixtures. The optimal
mole ratio of TETA/Cu 2+ is found to be 2.5/1 for preparing sub 3 nm CuNPs under
the MW irradiation, operated at 800 W for 1 min. The plasmonic absorption lambda
max demonstrated in UV-vis spectra are found to close to 200 nm for sub 3 nm
CuNPs, comparing to 500 ~ 600 nm for regular, larger CuNPs. The extremely low Tm
around 30 degrees C and the fusion/recrystallization sequence of sub 3 nm CuNPs
can be directly measured by their differential scanning calorimetry thermograms.
PMID- 29350199
TI - Cortical visual prostheses: from microstimulation to functional percept.
AB - Cortical visual prostheses are intended to restore vision by targeted electrical
stimulation of the visual cortex. The perception of spots of light, called
phosphenes, resulting from microstimulation of the visual pathway, suggests the
possibility of creating meaningful percept made of phosphenes. However, to date
electrical stimulation of V1 has still not resulted in perception of phosphenated
images that goes beyond punctate spots of light. In this review, we summarize the
clinical and experimental progress that has been made in generating phosphenes
and modulating their associated perceptual characteristics in human and macaque
primary visual cortex (V1). We focus specifically on the effects of different
microstimulation parameters on perception and we analyse key challenges facing
the generation of meaningful artificial percepts. Finally, we propose solutions
to these challenges based on the application of supervised learning of population
codes for spatial stimulation of visual cortex.
PMID- 29350200
TI - Leaf-templated, microwell-integrated microfluidic chips for high-throughput cell
experiments.
AB - As an alternative to conventional cell culture and animal testing, an organ-on-a
chip is applied to study the biological phenomena of organ development and
disease, as well as the interactions between human tissues and external stimuli
such as chemicals, forces and electricity. The pattern design of a microfluidic
channel is one of the key approaches to regulate cell growth and differentiation,
because these channels work as a crucial vasculature system to control the
fluidic flow throughout the organ-on-a-chip device. In this study, we introduce a
novel leaf-templated, microwell-integrated microfluidic chip for high-throughput
cell experiments, consisting of a leaf-venation layer for fluent fluid flow, and
a microwell-array layer for cell to reside. Computational fluid dynamics analysis
was carried out to study the fluidic flow within leaf-venation network, which was
further used to optimize the design of microwell arrays. A simple leaf-venation
mold-based microreplication method was developed to transfer the intact native
leaf venation network into leaf-venation layer and 3D printing technology was
used to fabricate the microwell-array layer. The layers were then assembled and
used for perfusion culture, showing that leaf-templated microfluidic channels
provided a sufficient culture medium for cells within each microwell. These
results indicate a novel and effective strategy to generate a biomimetic
microfluidic chip with an effective vascular transport system for high-throughput
cell experiments.
PMID- 29350201
TI - Moth-eye mimetic cytocompatible bactericidal nanotopography: a convergent design.
AB - The rapid emergence of antibiotic resistant bacteria has prompted the need for
radically different approaches to combat bacterial infections. Among these,
bioinspired surface topographies have emerged as an effective sustainable
strategy to deter bacterial infection. This study demonstrates the bactericidal
activity and cytocompatibility of the moth-eye mimetic topography produced by
thermal polymer nanoimprinting. The moth-eye topography was found to have
bactericidal capabilities against Gram negative and Gram positive bacteria.
Electron microscopy imaging revealed the bactericidal effect caused by mechanical
rupture of the bacteria wall inflicted by the topography on the adhered cells.
The cytocompatibility of the surfaces was evidenced by assessing the
proliferation and morphology of keratinocytes cultured on the nanotopography. The
technology meets important needs in medical implant technology for materials that
not only have good biocompatibility but also antibacterial properties for
reducing the risk of infections and related health complications.
PMID- 29350202
TI - Observation of low temperature metastable states in complex CaMn7O12.
AB - The low temperature magnetic behaviour of the multiferroic quadruple perovskite
CaMn7O12 is investigated. The magneto-caloric effect in this material is
presented for the first time. Along with the established magnetic transitions, T
N1 ~ 90 K and T N2 ~ 45 K, an anomaly at 20 K is observed in our dc
magnetization, ac susceptibility and dielectric measurements; below which, an
inverse magnetocaloric effect is also observed in our -DeltaS M (T) plots. The
neutron scattering measurements show minimal change between 10 K and 30 K in
static correlations, but a clear change in energy and linewidth of the magnetic
excitations is evident. The results suggest that only dynamic correlations change
across T M ~ 20 K. The existence of multiple magnetic interactions below 45 K,
with significant coupling between them, is demonstrated using an Arrott plot
analysis of our magnetic data. Compatible conclusions are drawn from
magnetocaloric plots. The peak change in isothermal magnetic entropy (-DeltaS M)
is 1.3 JK-1 kg-1 and the value of refrigeration capacity in CaMn7O12 is 34.5 J .
kg-1 at 7 T.
PMID- 29350203
TI - Subungual exostosis on index finger in a child.
PMID- 29350204
TI - PubMed indexing: Misconceptions.
PMID- 29350205
TI - Silymarin: An interesting modality in dermatological therapeutics.
PMID- 29350206
TI - Commentary on "Altered PIWI-LIKE 1 and PIWI-LIKE 2 mRNA expression in ejaculated
spermatozoa of men with impaired sperm characteristics".
PMID- 29350207
TI - Association between CYP2C19 and ABCB1 polymorphisms and clopidogrel resistance in
clopidogrel-treated Chinese patients.
AB - OBJECTIVE: To investigate the association between CYP2C19 and ABCB1 polymorphisms
and clopidogrel resistance (CR) in patients with cardiovascular disease in
Beijing district. METHODS: In total, 325 patients were enrolled in the study,
including 101 experimental group patients and 224 control group patients. The
experimental group was divided into CR group (n=30) and non-CR group (n=71)
according to the adenosine diphosphate (ADP)-induced platelet inhibition rate in
thromboelastography (TEG) (ADP-induced platelet inhibition rate of <30% was
defined as CR and rate of 30%-100% was defined as non-CR). Genotypes, including
CYP2C19*2, CYP2C19*3, CYP2C19*4, CYP2C19*5, CYP2C19*17, and ABCB1, were
determined using time-of-flight mass spectrometry (Clin-TOF) and Sanger
sequencing in all patients. RESULTS: In the experimental group, carriers of
CYP2C19 heterozygous (*1/*2, n=46; *1/*3, n=7), and mutation homozygous (*2/*2,
n=7; *2/*3, n=3; *3/*3, n=0) genotypes showed significantly lower ADP-induced
platelet inhibition rates than noncarriers (*1/*1, n=38; p=0.035 and 0.001,
respectively); the carriage of mutant CYP2C19*2 or *3 allele was significantly
associated with an increased risk of CR. In contrast, carriers of ABCB1
heterozygous (TC, n=50) showed significantly lower ADP-induced platelet
inhibition rates than noncarriers (CC, n=39, p=0.097), and there was no
significant correlation between ABCB1 genotypes and higher CR risk. CONCLUSION:
The carriage of CYP2C19*2 or *3 mutant allele was significantly associated with
attenuated platelet response to clopidogrel and increased CR risk. The carriage
of ABCB1 mutant allele was not significantly associated with CR risk.
PMID- 29350208
TI - Protective effect of paracetamol in doxorubicin-induced cardiotoxicity in
ischemia/reperfused isolated rat heart.
AB - OBJECTIVE: Doxorubicin (DOX) induces cardiac dysfunction. Paracetamol (APAP) has
also been established as an effective cardioprotective agent during
ischemia/reperfusion. Therefore, this study aims to evaluate the effect of APAP
on DOX-induced cardiotoxicity in ischemia/reperfused isolated rat heart. METHODS:
A total of 36 rats were equally divided into four groups: control, DOX (30 min,
20 uM DOX perfusion), APAP (15 min before and after ischemia, 0.35 mM APAP
perfusion), and DOX+APAP (perfused with the same protocol in DOX and APAP
groups). The isolated hearts were perfused according to the Langendorff method.
Cardiac parameters, including left ventricular developed pressure (LVDP), heart
rate (HR), coronary flow (CF), and rate pressure product (RPP; LVDP*HR) were
measured. Lactate dehydrogenase (LDH) concentration was also assessed. RESULTS:
At the end of the baseline period, the RPP, HR, and CF values were lower in the
DOX group than in the control group (p<0.01). Meanwhile, there were no
significant differences between the values of cardiac function parameters in the
DOX+APAP and control groups. In the reperfusion period, the RPP and CF values
were significantly increased in the DOX+APAP group compared with the DOX group
(p<0.05). Furthermore, the LDH concentration was decreased in the DOX+APAP group
compared with the DOX group. CONCLUSION: APAP perfusion protected the hearts
against DOX-induced cardiotoxicity in the baseline and ischemia/reperfusion
conditions. These findings can be explained by the effect of APAP on antioxidant
capacity and mitochondrial permeability transition pores.
PMID- 29350209
TI - Molecular basis for CENP-N recognition of CENP-A nucleosome on the human
kinetochore.
PMID- 29350210
TI - Response to: Comment on "Differences in Ventilatory Threshold for Exercise
Prescription in Outpatient Diabetic and Sarcopenic Obese Subjects".
PMID- 29350211
TI - Correction: A niche that triggers aggressiveness within BRCA1-IRIS overexpressing
triple negative tumors is supported by reciprocal interactions with the
microenvironment.
AB - [This corrects the article DOI: 10.18632/oncotarget.20892.].
PMID- 29350212
TI - Defining System Boundaries of an Institution Nitrogen Footprint.
AB - A nitrogen (N) footprint quantifies the amount of reactive nitrogen released to
the environment and can be measured at different scales. The N footprint of a
university includes activities and consumption within its geographic boundaries
as well as activities that support the institution. Determining system bounds of
an N footprint depends on the institution's mission and provides a common
baseline for comparison. A comparison of three scopes of the N footprint, which
describe how emissions are directly related to an institution's activities, was
conducted for seven institutions. Scopes follow the established definition for
the carbon footprint. In this article, the authors propose a new system bounds
definition (core campus versus adjunct). Two case studies were explored: how the
N footprint of Dickinson College changed with air travel, and how the N footprint
of the Marine Biological Laboratory changed with scientific research. Of the
three scopes, scope 3 was consistently the largest proportion of the N footprint
for all seven institutions. The core campus activities of Dickinson College made
up 99 percent of its N footprint, with air travel making up the remaining 1
percent. The Marine Biological Laboratory's core campus activities made up 51
percent of its N footprint and the scientific research made up the remaining 49
percent. Institutions should define system bounds based on their mission and stay
consistent with their boundaries following the baseline year. The core campus
footprint could be used to compare institution footprints using consistent system
bounds. How institutions define their boundaries will impact the recorded amount
of nitrogen as well as how the institution will set reduction strategies.
PMID- 29350213
TI - Erratum.
AB - [This corrects the article DOI: 10.1177/2382120516684829.].
PMID- 29350214
TI - Erratum.
AB - [This corrects the article DOI: 10.1177/2050313X17744072.].
PMID- 29350215
TI - Validation of prediction models: examining temporal and geographic stability of
baseline risk and estimated covariate effects.
AB - Background: Stability in baseline risk and estimated predictor effects both
geographically and temporally is a desirable property of clinical prediction
models. However, this issue has received little attention in the methodological
literature. Our objective was to examine methods for assessing temporal and
geographic heterogeneity in baseline risk and predictor effects in prediction
models. Methods: We studied 14,857 patients hospitalized with heart failure at 90
hospitals in Ontario, Canada, in two time periods. We focussed on geographic and
temporal variation in baseline risk (intercept) and predictor effects (regression
coefficients) of the EFFECT-HF mortality model for predicting 1-year mortality in
patients hospitalized for heart failure. We used random effects logistic
regression models for the 14,857 patients. Results: The baseline risk of
mortality displayed moderate geographic variation, with the hospital-specific
probability of 1-year mortality for a reference patient lying between 0.168 and
0.290 for 95% of hospitals. Furthermore, the odds of death were 11% lower in the
second period than in the first period. However, we found minimal geographic or
temporal variation in predictor effects. Among 11 tests of differences in time
for predictor variables, only one had a modestly significant P value (0.03).
Conclusions: This study illustrates how temporal and geographic heterogeneity of
prediction models can be assessed in settings with a large sample of patients
from a large number of centers at different time periods.
PMID- 29350216
TI - The Nitrogen Footprint Tool Network: A Multi-Institution Program To Reduce
Nitrogen Pollution.
AB - Anthropogenic sources of reactive nitrogen have local and global impacts on air
and water quality and detrimental effects on human and ecosystem health. This
article uses the Nitrogen Footprint Tool (NFT) to determine the amount of
nitrogen (N) released as a result of institutional consumption. The sectors
accounted for include food (consumption and upstream production), energy,
transportation, fertilizer, research animals, and agricultural research. The NFT
is then used for scenario analysis to manage and track reductions, which are
driven by the consumption behaviors of both the institution itself and its
constituent individuals. In this article, the first seven completed institution
nitrogen footprint results are presented. The Nitrogen Footprint Tool Network
aims to develop footprints for many institutions to encourage widespread upper
level management strategies that will create significant reductions in reactive
nitrogen released to the environment. Energy use and food purchases are the two
largest sectors contributing to institution nitrogen footprints. Ongoing efforts
by institutions to reduce greenhouse gas emissions also help to reduce the
nitrogen footprint, but the impact of food production on nitrogen pollution has
not been directly addressed by the higher education sustainability community. The
Nitrogen Footprint Tool Network found that institutions could reduce their
nitrogen footprints by optimizing food purchasing to reduce consumption of animal
products and minimize food waste, as well as by reducing dependence on fossil
fuels for energy.
PMID- 29350217
TI - An Integrated Tool for Calculating and Reducing Institution Carbon and Nitrogen
Footprints.
AB - The development of nitrogen footprint tools has allowed a range of entities to
calculate and reduce their contribution to nitrogen pollution, but these tools
represent just one aspect of environmental pollution. For example, institutions
have been calculating their carbon footprints to track and manage their
greenhouse gas emissions for over a decade. This article introduces an integrated
tool that institutions can use to calculate, track, and manage their nitrogen and
carbon footprints together. It presents the methodology for the combined tool,
describes several metrics for comparing institution nitrogen and carbon footprint
results, and discusses management strategies that reduce both the nitrogen and
carbon footprints. The data requirements for the two tools overlap substantially,
although integrating the two tools does necessitate the calculation of the carbon
footprint of food. Comparison results for five institutions suggest that the
institution nitrogen and carbon footprints correlate strongly, especially in the
utilities and food sectors. Scenario analyses indicate benefits to both
footprints from a range of utilities and food footprint reduction strategies.
Integrating these two footprints into a single tool will account for a broader
range of environmental impacts, reduce data entry and analysis, and promote
integrated management of institutional sustainability.
PMID- 29350218
TI - Comparing Institution Nitrogen Footprints: Metrics for Assessing and Tracking
Environmental Impact.
AB - When multiple institutions with strong sustainability initiatives use a new
environmental impact assessment tool, there is an impulse to compare. The first
seven institutions to calculate nitrogen footprints using the Nitrogen Footprint
Tool have worked collaboratively to improve calculation methods, share resources,
and suggest methods for reducing their footprints. This article compares those
seven institutions' results to reveal the common and unique drivers of
institution nitrogen footprints. The footprints were compared by scope and
sector, and the results were normalized by multiple factors (e.g., population,
amount of food served). The comparisons found many consistencies across the
footprints, including the large contribution of food. The comparisons identified
metrics that could be used to track progress, such as an overall indicator for
the nitrogen sustainability of food purchases. The comparisons also pointed to
differences in system bounds of the calculations, which are important to
standardize when comparing across institutions. The footprints were influenced by
factors both within and outside of the institutions' ability to control, such as
size, location, population, and campus use. However, these comparisons also point
to a pathway forward for standardizing nitrogen footprint tool calculations,
identifying metrics that can be used to track progress, and determining a
sustainable institution nitrogen footprint.
PMID- 29350219
TI - Reducing the Nitrogen Footprint of a Small Residential College.
AB - The release of reactive nitrogen contributes to its accumulation in the
environment, causing a variety of harmful effects. To measure Dickinson College's
contribution to nitrogen pollution, and quantify the potential to reduce its
contribution, we calculated the college's nitrogen footprint and simulated the
effects of selected nitrogen mitigation measures. The analysis was obtained using
the Nitrogen Footprint Tool, developed at the University of Virginia. Food
production is by far the largest contributor to Dickinson's footprint, followed
by heat and power. Transportation, sewage, and groundskeeping contribute
relatively small amounts. Breaking food down into different food categories, meat
and fish is the largest source of nitrogen, accounting for two-thirds of the food
footprint. Simulations of individual mitigation measures showed that measures
targeting food are the most impactful for reducing the college's nitrogen
footprint. Two policy scenarios that combine multiple measures, one representing
moderate action and the other more aggressive action, were also analyzed. They
are projected to reduce Dickinson's footprint by roughly 15 and 25 percent,
respectively, while reducing operating costs. Achieving these reductions would
require substantial changes in dietary choices by members of the campus
community.
PMID- 29350220
TI - Nephrotic syndrome in primary myelofibrosis with renal extramedullary
hematopoiesis and glomerulopathy in the JAK inhibitor era.
AB - Primary myelofibrosis (PMF) is an uncommon form of myeloproliferative neoplasm
(MPN) characterized by a proliferation of predominantly megakaryocytes and
granulocytes in the bone marrow that, in fully-developed disease, is associated
with reactive deposition of fibrous connective tissue, extramedullary
hematopoiesis (EMH), and splenomegaly. Kidney involvement is rare and clinically
presents with proteinuria, nephrotic syndrome, and renal insufficiency. Renal
damage can be due to EMH and glomerulopathy. Renal EMH presents three patterns:
infiltration of the interstitium with possible renal failure caused by functional
damage of parenchyma and vessels, infiltration of capsule and pericapsular
adipose tissue, and sclerosing mass-like lesions that can cause hydronephrosis
and hydroureter with obstructive uropathy and renal failure. Glomerulopathy
associated with PMF is rarely described, ranging from 1 month to 18 years from
diagnosis of the neoplasm to renal biopsy. It is characterized by expansion and
hypercellularity mesangial, segmental sclerosis, features of chronic thrombotic
microangiopathy (TMA), and intracapillary hematopoietic cells infiltrating in
absence of immune-mediated glomerulonephritis. We present a nephrotic syndrome in
PMF-related glomerulopathy, associated with EMH, without renal failure, in a
patient under treatment for 2 years with JAK2 inhibitor ruxolitinib. Despite
treatment, the patient died 7 months after renal biopsy. Nephrologists still know
very little about this topic and there is no homogeneous data about incidence,
pathogenesis, and optimal treatment of this poor prognostic PMF-associated
nephrotic syndrome. We focus on data in the literature in the hope of stimulating
hematologists, nephrologists, pathologists to future studies about the natural
history of renal involvement, useful for optimal management of this rare
pathology.
PMID- 29350221
TI - Assessing the Social and Environmental Costs of Institution Nitrogen Footprints.
AB - This article estimates the damage costs associated with the institutional
nitrogen (N) footprint and explores how this information could be used to create
more sustainable institutions. Potential damages associated with the release of
nitrogen oxides (NOx), ammonia (NH3), and nitrous oxide (N2O) to air and release
of nitrogen to water were estimated using existing values and a cost per unit of
nitrogen approach. These damage cost values were then applied to two
universities. Annual potential damage costs to human health, agriculture, and
natural ecosystems associated with the N footprint of institutions were $11.0
million (2014) at the University of Virginia (UVA) and $3.04 million at the
University of New Hampshire (UNH). Costs associated with the release of nitrogen
oxides to human health, in particular the use of coal-derived energy, were the
largest component of damage at UVA. At UNH the energy N footprint is much lower
because of a landfill cogeneration source, and thus the majority of damages were
associated with food production. Annual damages associated with release of
nitrogen from food production were very similar at the two universities ($1.80
million vs. $1.66 million at UVA and UNH, respectively). These damages also have
implications for the extent and scale at which the damages are felt. For example,
impacts to human health from energy and transportation are generally larger near
the power plants and roads, while impacts from food production can be distant
from the campus. Making this information available to institutions and
communities can improve their understanding of the damages associated with the
different nitrogen forms and sources, and inform decisions about nitrogen
reduction strategies.
PMID- 29350222
TI - A Prescription for Note Bloat: An Effective Progress Note Template.
AB - BACKGROUND: United States hospitals have widely adopted electronic health records
(EHRs). Despite the potential for EHRs to increase efficiency, there is concern
that documentation quality has suffered. OBJECTIVE: To examine the impact of an
educational session bundled with a progress note template on note quality,
length, and timeliness. DESIGN: A multicenter, nonrandomized prospective trial.
SETTING: Four academic hospitals across the United States. PARTICIPANTS: Intern
physicians on inpatient internal medicine rotations at participating hospitals.
INTERVENTION: A task force delivered a lecture on current issues with
documentation and suggested that interns use a newly designed best practice
progress note template when writing daily progress notes. MEASUREMENTS: Note
quality was rated using a tool designed by the task force comprising a general
impression score, the validated Physician Documentation Quality Instrument, 9
item version (PDQI-9), and a competency questionnaire. Reviewers documented
number of lines per note and time signed. RESULTS: Two hundred preintervention
and 199 postintervention notes were collected. Seventy percent of
postintervention notes used the template. Significant improvements were seen in
the general impression score, all domains of the PDQI-9, and multiple competency
items, including documentation of only relevant data, discussion of a discharge
plan, and being concise while adequately complete. Notes had approximately 25%
fewer lines and were signed on average 1.3 hours earlier in the day. CONCLUSIONS:
The bundled intervention for progress notes significantly improved the quality,
decreased the length, and resulted in earlier note completion across 4 academic
medical centers.
PMID- 29350223
TI - What Is Career Success for Academic Hospitalists? A Qualitative Analysis of Early
Career Faculty Perspectives.
AB - BACKGROUND: Understanding the concept of career success is critical for hospital
medicine groups seeking to create sustainably rewarding faculty positions.
Conceptual models of career success describe both extrinsic (compensation and
advancement) and intrinsic (career satisfaction and job satisfaction) domains.
How hospitalists define career success for themselves is not well understood. In
this study, we qualitatively explore perspectives on how early-career clinician
educators define career success. METHODS: We developed a semistructured interview
tool of open-ended questions validated by using cognitive interviewing.
Transcribed interviews were conducted with 17 early-career academic hospitalists
from 3 medical centers to thematic saturation. A mixed deductiveinductive,
qualitative, analytic approach was used to code and map themes to the theoretical
framework. RESULTS: The single most dominant theme participants described was
"excitement about daily work," which mapped to the job satisfaction organizing
theme. Participants frequently expressed the importance of "being respected and
recognized" and "dissemination of work," which were within the career
satisfaction organizing theme. The extrinsic organizing themes of advancement and
compensation were described as less important contributors to an individual's
sense of career success. Ambivalence toward the "academic value of clinical
work," "scholarship," and especially "promotion" represented unexpected themes.
CONCLUSIONS: The future of academic hospital medicine is predicated upon faculty
finding career success. Clinician-educator hospitalists view some traditional
markers of career advancement as relevant to success. However, early-career
faculty question the importance of some traditional external markers to their
personal definitions of success. This work suggests that the selfconcept of
career success is complex and may not be captured by traditional academic metrics
and milestones.
PMID- 29350225
TI - Visible-light-induced multicomponent cascade cycloaddition involving N-propargyl
aromatic amines, diaryliodonium salts and sulfur dioxide: rapid access to 3
arylsulfonylquinolines.
AB - A visible-light-induced, Eosin Y catalyzed three-component synthesis of 3
arylsulfonylquinoline derivatives through N-propargyl aromatic amines,
diaryliodonium salts and sulfur dioxide has been discovered. This transformation
represents an efficient and attractive method for the straightforward synthesis
of 3-arylsulfonylquinoline derivatives via the formation of C-S bonds and
quinolines in one step. In addition, it exhibits good substrate scope and
functional group tolerance. The use of easy-to-handle diaryliodonium salts,
sulfur dioxide sources and the cheap photocatalyst Eosin Y together with facile
operation at room temperature makes this protocol very practical.
PMID- 29350226
TI - The ortho-benzyne cation is not planar.
AB - A recent review on the photoionisation of the C6H4 isomer ortho-benzyne suggests
that bands reported in earlier photoelectron spectra might be due to side
products or contaminations, while computations raise doubts, whether the cation
has a planar geometry. We therefore reinvestigate the photoionisation of ortho
benzyne, generated by pyrolysis from benzocyclobutenedione, by photoion mass
selected threshold photoelectron (ms-TPE) spectroscopy using synchrotron
radiation. The experiments are accompanied by a theoretical study that
investigates the structure of the ortho-benzyne cation systematically as a
function of the computational method, up to CASPT2(11,14) ab initio computations.
Our study leads to a re-evaluation of the ionisation energy of ortho-benzyne. It
reveals that the ortho-benzyne cation has indeed a twisted C2 geometry rather
than a C2v structure. A vertical ionisation energy IEvert of 9.77 eV and an
adiabatic ionisation energy of IEad = 9.56 eV are computed for ortho-benzyne. A
Franck-Condon simulation of the photoelectron spectrum based on the CASPT2
results and including three electronic states of the cation is in agreement with
the experiment and yields IEad = 9.51 eV (+50 meV/-100 meV). Since this value is
in contrast with previous work, the ionisation energy has to be revised based on
our study. Computational methods based on density functional theory give a
reasonable description of the cationic ground state, but fail for the
corresponding excited electronic states that are indispensible for a proper
assignment of the photoelectron spectrum.
PMID- 29350228
TI - Correction: Films of bacteria at interfaces: three stages of behaviour.
AB - Correction for 'Films of bacteria at interfaces: three stages of behaviour' by
Liana Vaccari et al., Soft Matter, 2015, 11, 6062-6074.
PMID- 29350227
TI - Albusnodin: an acetylated lasso peptide from Streptomyces albus.
AB - We describe a lasso peptide, albusnodin, that is post-translationally modified
with an acetyl group, the first example of a lasso peptide with this
modification. Using heterologous expression, we further show that the
acetyltransferase colocalized with the albusnodin gene cluster is required for
the biosynthesis of this lasso peptide. This type of lasso peptide is widespread
in Actinobacteria with 44 examples found in currently sequenced genomes.
PMID- 29350229
TI - Aggregate evolution in aqueous solutions of a Gemini surfactant derived from
dehydroabietic acid.
AB - Innovations in surfactant structure are a feasible way to probe molecular self
assembly principles. Herein, the solution behaviour of a newly synthesized Gemini
surfactant derived from dehydroabietic acid, abbreviated R-(EO)-E-R, was
investigated using surface tension, fluorescence, isothermal titration
calorimetry (ITC), rheology, freeze-fracture transmission electron microscopy (FF
TEM) and cryogenic transmission electron microscopy (cryo-TEM) methods. R-(EO)-E
R has two large, rigid hydrophobic groups. At low concentrations, R-(EO)-E-R
forms micelles with an aggregation number of approximately 10, which is smaller
than those of Gemini surfactants containing flexible alkyl tails. In addition,
the micellization process is less exothermic because of the rigidity of the
hydrophobic portions. As the concentration increases, R-(EO)-E-R without any
additives forms wormlike micelles, endowing the solution with an obvious
viscoelasticity. Further increases in the concentration lead to the coexistence
of single-walled vesicles, double-walled vesicles and rarely observed long,
tubular vesicles. This behaviour is attributed to the two large, rigid
hydrophobic groups of R-(EO)-E-R, which increase the density of the hydrophobic
portion around the ionic head groups and facilitate the formation of aggregates
with lower curvatures and asymmetric morphology. Surfactants containing rigid
hydrophobic portions are expected to result in more delicate, self-assembled
morphologies with broad applications.
PMID- 29350230
TI - Selective growth of two-dimensional phosphorene on catalyst surface.
AB - Although the study of black phosphorene (BP) and its isomers has attracted
enormous attention, the method of synthesizing high-quality samples in a large
area is still pending. Here we explore the potential of using the chemical vapor
deposition method to synthesize large-area two-dimensional (2D) phosphorene films
on metal surfaces. Our ab initio calculations show that BP can be synthesized by
using tin (Sn) as a catalyst, while one of its isomers, blue phosphorene (BLP),
is very possible to be synthesized by using most other metals, such as Ag and Au.
Besides, our study also suggests that the large binding energy between the 2D
phosphorene and the active metal substrate may prohibit the exfoliation of the 2D
phosphorene for real applications and, therefore, tin, silver and gold are
predicted to be the most suitable catalysts for the synthesis of BP and BLP.
PMID- 29350231
TI - Tuning the sensitivity of lanthanide-activated NIR nanothermometers in the
biological windows.
AB - Lanthanide-activated SrF2 nanoparticles with a multishell architecture were
investigated as optical thermometers in the biological windows. A ratiometric
approach based on the relative changes in the intensities of different lanthanide
(Nd3+ and Yb3+) NIR emissions was applied to investigate the thermometric
properties of the nanoparticles. It was found that an appropriate doping with
Er3+ ions can increase the thermometric properties of the Nd3+-Yb3+ coupled
systems. In addition, a core containing Yb3+ and Tm3+ can generate light in the
visible and UV regions upon near-infrared (NIR) laser excitation at 980 nm. The
multishell structure combined with the rational choice of dopants proves to be
particularly important to control and enhance the performance of nanoparticles as
NIR nanothermometers.
PMID- 29350232
TI - Impact of droplets on immiscible liquid films.
AB - The impact of droplets on liquid films is a ubiquitous phenomenon not only in
nature but also in many industrial applications. Compared to the widely-studied
impact of droplets on films of identical fluids, the impact of droplets on
immiscible films has received far less attention. In the present work, we show
using high-speed imaging that immiscibility has a profound effect on the impact
dynamics. The impact of a water droplet on an oil film leads to the formation of
a compound crown followed by a central jet, whereas that of an oil droplet on a
water film results in rapid spreading on the film surface driven by a large,
positive spreading factor. In the former scenario, the central jet occurs due to
the severe stretching of the droplet during the formation of the crown and then
the retraction of the droplet by capillarity, which leads to the collision of
fluid at the impact point. A model for the elongation dynamics of the central jet
is proposed based on energy conservation. The effects of key parameters
controlling the impact process are analysed, including the droplet Ohnesorge and
Weber numbers, the viscosity ratio, and the dimensionless film thickness.
Different impact outcomes are discussed, such as bouncing, deposition, and
oscillation of the impact droplet, the formation and collapse of the compound
crown, and the formation and tip-pinching of the central jet. This study not only
provides physical insights into the impact dynamics, but could also facilitate
the control and optimisation of the droplet impact process in a number of
applications as highlighted herein.
PMID- 29350233
TI - Stacking faults in Zr(Fe, Cr)2 Laves structured secondary phase particle in
Zircaloy-4 alloy.
AB - Stacking faults (SFs) in secondary phase particles (SPPs), which generally
crystallize in the Laves phase in Zircaloy-4 (Zr-4) alloy, have been frequently
observed by researchers. However, few investigations on the nano-scale structure
of SFs have been carried out. In the present study, an SF containing C14
structured SPP, which located at grain boundaries (GBs) in the alpha-Zr matrix,
was chosen to be investigated, for its particular substructure as well as
location, aiming to reveal the nature of the SFs in the SPPs in Zr-4 alloy. It
was indicated that the SFs in the C14 structured SPP actually existed in the
local C36 structured Laves phase, for their similarities in crystallography. The
C14 -> C36 phase transformation, which was driven by synchroshearing among the
(0001) basal planes, was the formation mechanism of the SFs in the SPPs. By
analyzing the strained regions near the SPP, a model for understanding the
driving force of the synchroshear was proposed: the interaction between SPP and
GB resulted in the Zener pinning effect, leading to the shearing parallel to the
(0001) basal planes of the C14 structured SPP, and the synchroshear was therefore
activated.
PMID- 29350234
TI - Dissociative electron attachment and anion-induced dimerization in pyruvic acid.
AB - We report partial cross sections for the dissociative electron attachment to
pyruvic acid. A rich fragmentation dynamics is observed. Electronic structure
calculations facilitate the identification of complex rearrangement reactions
that occur during the dissociation. Furthermore, a number of fragment anions
produced at electron energies close to 0 eV are observed, that cannot originate
from single electron-molecule collisions. We ascribe their production to
secondary reactions of the transient anions with neutral molecules. Such
reactions turn out to be unusually efficient; the most probable reason for this
is that they proceed via the formation of a double-hydrogen-bonded complex
followed by an ultrafast proton transfer between the reaction partners.
PMID- 29350235
TI - Pressure induced photoluminescence modulation in a wide range and synthesis of
monodispersed ternary AgCuS nanocrystal based on Ag2S nanocrystals.
AB - Binary Ag2S nanocrystals (NCs) have many potential optical applications because
of their low toxicity, narrow direct band gaps and near-infrared
photoluminescence (PL) with high emission efficiency. However, due to its small
exciton Bohr radius (2.2 nm), the PL spectra of Ag2S NCs can only be modulated
below ~1200 nm with increasing particle size. Meanwhile, ternary silver copper
chalcogenides (AgCuX, X = S, Se) have also attracted increased attention in
recent years. Temperature-dependent structural phase transformation leads
electrical transport to exhibit fascinating transitions between p and n type
conduction, which makes AgCuS and AgCuSe ideal materials for diode or transistor
devices. Nevertheless, the traditional method to synthesize these materials is
mainly through melting the mixture of Ag, Cu and S/Se powder under extremely high
reaction temperatures (973-1373 K) and long reaction time, forming a bulk
product. Therefore, the synthesis of high quality monodispersed and size-tunable
AgCuS or AgCuSe NCs is still a challenge. To address these issues, in this paper,
we report using Ag2S NCs as a template, a method to synthesize monodispersed and
size-tunable beta-AgCuS NCs via ion exchange and diffusion processes. Similarly,
monodispersed beta-AgCuSe NCs were also synthesized by this simple and
reproducible strategy. This synthetic method opens new avenues for investigating
the size-, morphology- and temperature-dependent phase transitions of these
ternary AgCuS and AgCuSe materials. Thus, the corresponding electrical transport
between p and n type conduction can be studied in the future. Furthermore, we
systematically investigated the pressure-dependent PL properties and band gap
modulation of monodispersed Ag2S NCs using in situ high pressure PL and
absorption spectroscopy. We found that the PL peak of 6.0 nm for Ag2S NCs could
be easily adjusted from ~1200 to 1900 nm with increasing pressure from 0 to 5.1
GPa, which greatly extends the wavelength range of the PL peak beyond that of
other approaches.
PMID- 29350236
TI - Dose optimization of total or partial skin electron irradiation by
thermoluminescent dosimetry.
AB - BACKGROUND: Due to the complex surface of the human body, total or partial skin
irradiation using large electron fields is challenging. The aim of the present
study was to quantify the magnitude of dose optimization required after the
application of standard fields. METHODS: Total skin electron irradiation (TSEI)
was applied using the Stanford technique with six dual-fields. Patients
presenting with localized lesions were treated with partial skin electron
irradiation (PSEI) using large electron fields, which were individually adapted.
In order to verify and validate the dose distribution, in vivo dosimetry with
thermoluminescent dosimeters (TLD) was performed during the first treatment
fraction to detect potential dose heterogeneity and to allow for an individual
dose optimization with adjustment of the monitor units (MU). RESULTS: Between
1984 and 2017, a total of 58 patients were treated: 31 patients received TSEI
using 12 treatment fields, while 27 patients underwent PSEI and were treated with
4-8 treatment fields. After evaluation of the dosimetric results, an individual
dose optimization was necessary in 21 patients. Of these, 7 patients received
TSEI (7/31). Monitor units (MU) needed to be corrected by a mean value of 117 MU
(+/-105, range 18-290) uniformly for all 12 treatment fields, corresponding to a
mean relative change of 12% of the prescribed MU. In comparison, the other 14
patients received PSEI (14/27) and the mean adjustment of monitor units was 282
MU (+/-144, range 59-500) to single or multiple fields, corresponding to a mean
relative change of 22% of the prescribed MU. A second dose optimization to obtain
a satisfying dose at the prescription point was need in 5 patients. CONCLUSIONS:
Thermoluminescent dosimetry allows an individual dose optimization in TSEI and
PSEI to enable a reliable adjustment of the MUs to obtain the prescription dose.
Especially in PSEI in vivo dosimetry is of fundamental importance.
PMID- 29350237
TI - Long-term changes in multimodal intensive tinnitus therapy : A 5-year follow-up.
AB - BACKGROUND: We present 5-year follow-up data for tinnitus-specific and comorbid
depressive symptoms as well as stress-related outcome variables of an intensive
multimodal 7-day tinnitus therapy. METHOD: Tinnitus burden (Tinnitus
Questionnaire), stress (Perceived Stress Questionnaire), and depressive
symptomatology (General Depression Scale) were measured at the 5-year follow-up
after a multimodal intensive 7-day intervention. In all, 94 patients participated
in the study. RESULTS: All outcome variables showed significant improvement at
the end of the 7-day intensive treatment. These effects remained significant
after 5 years. CONCLUSION: The results of the present study support the
effectiveness of the 7-day multimodal intensive therapy for tinnitus.
Posttreatment improvements were related to both tinnitus burden as well as stress
and depressive symptoms and were maintained at the 5-year follow-up.
PMID- 29350238
TI - [Female patient with pulsatile tinnitus].
PMID- 29350239
TI - [The ABC guide for the treatment of posterior shoulder instability].
AB - BACKGROUND: Posterior glenohumeral instability (PGHI) is an often unrecognized or
misdiagnosed type of shoulder instability due to its heterogenic clinical and
radiological presentation. CLASSIFICATION: The ABC classification for PGHI is
based on the different pathomechanisms and recommended treatment standards and is
therefore a guide to finding the correct diagnosis and therapy for affected
patients. There are different types of PGHI: A (first time), B (dynamic), C
(static). These groups are further classified based on pathomechanical
principles: A1: subluxation, A2: dislocation; B1: functional, B2: structural; C1:
constitutional, C2: acquired. THERAPY: In patients with type 1 PGHI (A1, B1, C1)
conservative treatment is recommended while in patients with type 2 PGHI (A2, B2,
C2) surgical treatment can be considered based on structural defects, clinical
symptoms, chronicity, age, functional demand, and patient-specific health status.
In addition it has to be considered, that there is the possibility of coexisting
or overlapping subtypes as well as the chance of progression from one category
into another over time.
PMID- 29350240
TI - Left ventricular endocardial pacing for the critically ill.
PMID- 29350241
TI - The airway occlusion pressure (P0.1) to monitor respiratory drive during
mechanical ventilation: increasing awareness of a not-so-new problem.
PMID- 29350242
TI - Is there a single non-painful procedure in the intensive care unit? It depends!
PMID- 29350243
TI - Current opinions on nephrolithiasis associated with primary hyperparathyroidism.
AB - Nephrolithiasis is a common urological disease and could be secondary to primary
hyperparathyroidism (PHPT). PHPT is traditionally characterised with
hypercalcaemia. Recently, a normocalcemic PHPT has been officially recognised at
the International Workshops. Regarding this new phenotype, nephrolithiasis is
frequently found in studies that evaluate low bone mass. However, until now, no
study on aetiology of nephrolithiasis considered normocalcemic PHPT.
Hypercalciuria related to PHPT is considered as an important risk factor of stone
formation in hypercalcemic PHPT, but the precise relationships between
hypercalcemic PHPT and nephrolithiasis and between normocalcemic PHPT and
nephrolithiasis remain unclear. In patients with hypercalcemic PHPT, after a
surgical cure of PHPT, the renal calcium excretion and stone recurrence rate
reduce but remain higher above health controls. This finding implies that
abnormalities not caused by PHPT also probably affect stone formation. According
to the new guideline, the presence of stones indicates the need for
parathyroidectomy in patients with either hypercalcemic or normocalcemic PHPT
unless contraindications exist. Patients with contraindications for
parathyroidectomy or those who do not want to receive parathyroidectomy should be
monitored for signs of disease progression and given of medical management.
Moreover, due to decreased but significantly higher frequency of nephrolithiasis
above those of healthy controls, patients with nephrolithiasis associated with
PHPT after parathyroidectomy still should be motivated to explore strategies to
prevent stone occurrence.
PMID- 29350245
TI - Chitinophaga caseinilytica sp. nov., a casein hydrolysing bacterium isolated from
forest soil.
AB - A novel casein hydrolysing bacterium designated strain S-52T was isolated from
Kyonggi University forest soil. Cells were strictly aerobic, Gram stain-negative,
oxidase- and catalase- positive, non-motile, non-spore-forming, rod-shaped, and
golden-yellow-pigmented. Strain S-52T hydrolysed casein. It was able to grow at
20-37 degrees C (optimum 25-32 degrees C), pH 6.5-11.0 (optimum 7-9.5), and at
3% (w/v) NaCl concentration. Strain exhibits flexirubin-type pigments.
Phylogenetic analysis based on 16S rRNA gene sequence revealed that strain S-52T
formed a lineage within the genus Chitinophaga that was distinct from other
species of the genus. Closest member was Chitinophaga barathri YLT18T (97.16% 16
S rRNA gene sequence similarity). The major cellular fatty acids were iso-C15:0,
C16:1omega5c, iso-C17:0 3-OH, and summed feature 3 (C16:1omega7c and/or C16:
1omega6c). MK-7 was sole respiratory quinone. The major polar lipid was
phosphatidylethanolamine. The DNA G + C content of strain S-52T was 48.8 mol%.
DNA-DNA relatedness of strain S-52T with Chitinophaga barathri was 42.5%. On the
basis of phenotypic, genotypic, phylogenetic, and chemotaxonomic
characterization, S-52T represents a novel species in the genus Chitinophaga, for
which the name Chitinophaga caseinilytica sp. nov. is proposed. The type strain
is S-52T (= KEMB 9005-540T = KACC 19118T = NBRC 112679T).
PMID- 29350244
TI - Autophagy-related (ATG) 11, ATG9 and the phosphatidylinositol 3-kinase control
ATG2-mediated formation of autophagosomes in Arabidopsis.
AB - KEY MESSAGE: Using quantitative assays for autophagy, we analyzed 4 classes of
atg mutants, discovered new atg2 phenotypes and ATG gene interactions, and
proposed a model of autophagosome formation in plants. Plant and other eukaryotic
cells use autophagy to target cytoplasmic constituents for degradation in the
vacuole. Autophagy is regulated and executed by a conserved set of proteins
called autophagy-related (ATG). In Arabidopsis, several groups of ATG proteins
have been characterized using genetic approaches. However, the genetic
interactions between ATG genes have not been established and the relationship
between different ATG groups in plants remains unclear. Here we analyzed atg2,
atg7, atg9, and atg11 mutants and their double mutants at the physiological,
biochemical, and subcellular levels. Involvement of phosphatidylinositol 3-kinase
(PI3K) in autophagy was also tested using wortmannin, a PI3K inhibitor. Our
mutant analysis using autophagy markers showed that atg7 and atg2 phenotypes are
more severe than those of atg11 and atg9. Unlike other mutants, atg2 cells
accumulated several autophagic vesicles that could not be delivered to the
vacuole. Analysis of atg double mutants, combined with wortmannin treatment,
indicated that ATG11, PI3K, and ATG9 act upstream of ATG2. Our data support a
model in which plant ATG1 and PI3K complexes play a role in the initiation of
autophagy, whereas ATG2 is involved in a later step during the biogenesis of
autophagic vesicles.
PMID- 29350246
TI - Data-Driven Quality Improvement Project to Increase the Value of the Congenital
Echocardiographic Report.
AB - Echocardiography is the primary diagnostic modality for congenital heart disease
patients. The written report is used to communicate with the care team and
organization is often divided into the body with detailed findings and the
conclusions with important findings summarized. Strategies to increase workflow
efficiency include batch writing of reports after performance of multiple
echocardiograms and the use of report templates which may contribute to
discrepancies within report leading to potential downstream medical errors. The
aim of this project was to measure the rate of inconsistencies in the
echocardiogram reports and through an iterative series of process improvement
decrease this rate while maintaining sonographer efficiency and diagnostic
accuracy. The discrepancy rate, diagnostic error rate, and sonographer
productivity were collected one-year prior and during the iterative quality
improvement process. The primary outcome and discrepancies in reports were
determined by two reviewers: an experienced pediatric echocardiographic
cardiologist and a senior sonographer. Minor discrepancies were defined as
contradictions between the body and the conclusion of the report that were
unlikely to affect patient care. Major discrepancies were defined as
discrepancies between the body and the conclusion that had significant potential
to affect patient care. Sonographer productivity was measured as studies per
sonographer per month. Our primary intervention was to initiate a quarterly QI
meeting and to decrease the batch writing of preliminary echocardiogram reports.
No major discrepancies were identified pre- or post-intervention. The minor
discrepancies decreased from 40.7 to 6%. Sonographer productivity was not
significantly changed with a slight increase from 100 studies/sonographer/month
during the baseline to 101 studies/sonographer/month during the intervention.
There was no change in major or minor diagnostic error rate. Our quality
improvement intervention increased the value of our reports by significantly
decreasing minor discrepancies without negatively impacting sonographer
productivity or diagnostic accuracy.
PMID- 29350247
TI - Prolonged PR Interval at Birth Predicting the High Occurrence of Fatal
Atrioventricular Block in Hypoplastic Left Heart Syndrome.
AB - Infants with hypoplastic left heart syndrome (HLHS) are at high mortality
especially when they are associated with bradyarrhythmias. However, the risk
factor of developing high-grade atrioventricular block (HAVB) is still unclear.
Seventy-three patients with HLHS in our institutions from 2002 to 2011 were
enrolled. The survival rate was assessed by the anatomical types, treatments,
occurrence of HAVB, severe tricuspid regurgitation (TR), and restrictive atrial
septal defect (ASD) along with electrocardiogram findings at birth. There were 23
(32%) cardiogenic and 7 (10%) non-cardiogenic deaths. The occurrence rate of HAVB
but not severe TR or restrictive ASD was higher in 30 deceased patients than in
43 survived patients [7 (23%) vs. 1 (2.3%), p = 0.0038]. The overall mortality
rate was higher in patients with HAVB than in those without it (p = 0.0002). Of 7
deceased patients with HAVB, 6 HAVB occurred within 10 days post-surgery, and 3
HAVB led to the early death. The mortality rate of patients with prolonged PR (>=
0.15 s) but not wide QRS (> 0.08 s) or prolonged QTc (> 0.43 s) at birth was
higher than each without it (p = 0.0106). Multivariate analysis indicated that
prolonged PR but no other variables was independently associated with the
mortality (hazard ratio: 2.948, p = 0.0104). Prolonged PR at birth in HLHS
infants predicts the development of fatal HAVB.
PMID- 29350248
TI - Natural variation and genetic make-up of leaf blade area in spring barley.
AB - KEY MESSAGE: GWAS analysis for leaf blade area (LA) revealed intriguing genomic
regions associated with putatively novel QTL and known plant stature-related
phytohormone and sugar-related genes. Despite long-standing studies in the morpho
physiological characters of leaf blade area (LA) in cereal crops, advanced
genetic studies to explore its natural variation are lacking. The importance of
modifying LA in improving cereal grain yield and the genes controlling leaf
traits have been well studied in rice but not in temperate cereals. To better
understand the natural genetic variation of LA at four developmental stages, main
culm LA was measured from 215 worldwide spring barleys including 92 photoperiod
sensitive accessions [PHOTOPERIOD RESPONSE LOCUS 1 (Ppd-H1)] and 123 accessions
with reduced photoperiod sensitivity (ppd-H1) locus under controlled greenhouse
conditions (long-day; 16/8 h; ~ 20/~ 16 degrees C day/night). The LA of Ppd-H1
carrying accessions was always smaller than in ppd-H1-carrying accessions. We
found that nine SNPs from the Ppd-H1 gene were present in the collection of which
marker 9 (M9; G/T in the CCT-domain) showed the most significant and consistent
effect on LA at all studied developmental stages. Genome-wide association scans
(GWAS) showed that the accessions carrying the ppd-H1 allele T/M9 (late heading)
possessed more genetic variation in LA than the Ppd-H1 group carrying G/M9 (early
heading). Several QTL with major effects on LA variation were found close to
plant stature-related heading time, phytohormone- and sugar-related genes. The
results provide evidence that natural variation of LA is an important source for
improving grain yield, adaptation and canopy architecture of temperate cereals.
PMID- 29350249
TI - Efficacy of phloroglucinol for treatment of abdominal pain: a systematic review
of literature and meta-analysis of randomised controlled trials versus placebo.
AB - AIM: Phloroglucinol is a musculotropic anti-spasmodic drug. It is frequently
prescribed in many European countries with a considerable cost for health
services. The purpose of this study was to review the existing randomised
controlled trials (RCT) comparing the efficacy of phloroglucinol treating
abdominal pain versus placebo. METHODS: A literature search was carried out up to
May 2017 to select RCT comparing the effect of phloroglucinol versus placebo with
intensity of abdominal pain as an endpoint. Studies concerning obstetric or
gynaecologic-related pain were not included. RESULTS: Three RCT were included and
then analysed for risk of bias and meta-analysed. Only one RCT found that
phloroglucinol was superior to placebo, although with a high risk of bias. The
meta-analysis found a risk ratio of 1.10 (95% CI 0.95, 1.27) with no statistical
significance. DISCUSSION: There is insufficient data to justify the wide-spread
prescription of phloroglucinol for alleviating abdominal pain.
PMID- 29350250
TI - [Abdominal injuries in polytraumatized adults : Systematic review].
AB - Abdominal injuries are potentially life-threatening and occur in 20-25% of all
polytraumatized patients. Blunt trauma is the main mechanism. The liver and
spleen are most commonly injured and much less often the intestines. The clinical
evaluation proves equivocal in many cases; therefore, the gold standard is
computed tomography (CT), which has been increasingly used even in
hemodynamically weakly stable or sometimes even unstable patients because it
promptly provides precise diagnostic findings, which present the basis for
successful therapy. Hemodynamically unstable patients always need an exploratory
laparotomy (EL). An EL should also be carried out with a positive focused
assessment with sonography for trauma (FAST) or CT for severe parenchymal
lesions, hollow organ lesions, intraperitoneal bladder lesions, peritonitis and
organ evisceration, impalement injuries and lesions of the abdominal fascia.
Hemodynamically stable patients without signs of peritonitis and a lack of such
findings can often be treated conservatively irrespective of the extent of an
injury. Angiography (and if needed embolization) can additionally be
diagnostically and therapeutically utilized.
PMID- 29350251
TI - Pyramidal cell-selective GluN1 knockout causes impairments in salience
attribution and related EEG activity.
AB - Schizophrenia is a disabling psychiatric disease characterized by symptoms
including hallucinations, delusions, social withdrawal, loss of pleasure, and
inappropriate affect. Although schizophrenia is marked by dysfunction in
dopaminergic and glutamatergic signaling, it is not presently clear how these
dysfunctions give rise to symptoms. The aberrant salience hypothesis of
schizophrenia argues that abnormal attribution of motivational salience to
stimuli is one of the main contributors to both positive and negative symptoms of
schizophrenia. The proposed mechanisms for this hypothesis are overactive
striatal dopaminergic and hypoactive glutamatergic signaling. The current study
assessed salience attribution in mice (n = 72) using an oddball paradigm in which
an infrequent stimulus either co-occurred with shock (conditioned group) or was
presented alone (non-conditioned group). Behavioral response (freezing) and
electroencephalogram (whole brain and amygdala) were used to assess salience
attribution. Mice with pyramidal cell-selective knockout of ionotropic glutamate
receptors (GluN1) were used to reproduce a prominent physiological change
involved in schizophrenia. Non-conditioned knockout mice froze significantly more
in response to the unpaired stimulus than non-conditioned wild-type mice,
suggesting that this irrelevant cue acquired motivational salience for the
knockouts. In accordance with this finding, low-frequency event-related spectral
perturbation was significantly increased in non-conditioned knockout mice
relative to both conditioned knockout and non-conditioned wild-type mice. These
results suggest that pyramidal cell-selective GluN1 knockout leads to
inappropriate attribution of salience for irrelevant stimuli as characterized by
abnormalities in both behavior and brain circuitry functions.
PMID- 29350252
TI - Risk factors of patients with pocket infection.
PMID- 29350253
TI - Direct transfer of STEMI patients to cardiac catheterization laboratory :
Prognostic relevance for in-hospital mortality.
AB - BACKGROUND: Although the incidence of acute myocardial infarction and in-hospital
mortality after ST-elevation myocardial infarction (STEMI) has declined
substantially in countries that have established primary percutaneous coronary
interventions (pPCI) over the past two decades, coronary artery disease remains a
major cause of morbidity and mortality worldwide. We aimed to examine whether the
direct transfer of STEMI patients to the cardiac catheterization laboratory (CCL)
had a prognostic effect on in-hospital mortality in patients who underwent pPCI
after STEMI. METHODS: The in-house mortality of STEMI patients who underwent pPCI
was assessed at the Department of Cardiology, Harzklinik Goslar, Germany, between
April 2013 and June 2017. RESULTS: We enrolled 312 STEMI patients, with a mean
age of 67.1 +/- 13.4 years, of whom 211 (71%) were male. The all-cause in
hospital mortality was 10% (n = 31 patients). A total of 298 (95%) patients were
directly transferred to the CCL. while 14 patients (5%) with STEMI were not
directly transferred to the CCL (tCCL) but were taken to the emergency department
(tED). In the tCCL group, 18 patients (6%) died during the hospital stay,
compared with 11 patients (79%) in the tED STEMI group; thus, the in-hospital
mortality rate was significantly higher (p < 0.0001) in the tED group.
CONCLUSION: Our monocentric cohort highlights and confirms the clinical
importance of the direct transfer of patients with STEMI to the CCL. This
approach is associated with a significant decrease in in-hospital mortality as
compared with the tED approach.
PMID- 29350254
TI - Sacubitril/valsartan for heart failure with reduced left ventricular ejection
fraction : A retrospective cohort study.
AB - BACKGROUND: The combination drug sacubitril/valsartan was reported to be superior
to enalapril in reducing all-cause death, cardiovascular mortality, and heart
failure (HF) hospitalizations in patients with cardiac insufficiency and reduced
left ventricular ejection fraction (HFREF) with NYHA class II-IV. METHODS: Our
retrospective cohort study aimed to assess the effects of sacubitril/valsartan in
addition to a beta-blocker and mineral receptor antagonist (MRA) in a group of
HFREF patients with NYHA class II-III HF vs. conventional therapy (ACE inhibitor
or angiotensin II receptor blocker added to a beta-blocker plus an MRA)
administered to a control group of HFREF patients with comparable clinical
features. In both groups, treatment was supplemented by a loop diuretic, usually
furosemide, at variable doses. The primary outcomes were all-cause death and HF
hospitalizations. Safety outcomes were symptomatic hypotension, angioedema,
hyperkalemia, and worsening renal function. RESULTS: Mortality at 6 months was
6.8% in patients taking sacubitril/valsartan vs. 34% in those on conventional
therapy (odds ratio [OR] = 0.14; 95% CI: 0.04-0.49). Moreover, there was a 4.5%
rate of HF hospitalizations in the sacubitril/valsartan group vs. 59% in the
control group (OR = 0.03; 95% CI: 0.01-0.14). Safety outcomes were comparable in
the two groups, although hypotension (systolic blood pressure < 100 mm Hg) was
found in 15.9% of patients in the sacubitril/valsartan group vs. 5.7% in the
control group (OR = 3.14; 95% CI: 0.94-10.55). CONCLUSION: Sacubitril/valsartan
offered strong protection against all-cause death and HF hospitalizations at 6
months without any significant side effects. To validate this efficacious
molecule, further postmarketing observational studies, focusing mainly on
hypotension and angioedema are warranted.
PMID- 29350255
TI - Nuclear magnetic resonance and high-performance liquid chromatography techniques
for the characterization of bioactive compounds from Humulus lupulus L. (hop).
AB - Humulus lupulus L. (hop) represents one of the most cultivated crops, it being a
key ingredient in the brewing process. Many health-related properties have been
described for hop extracts, making this plant gain more interest in the field of
pharmaceutical and nutraceutical research. Among the analytical tools available
for the phytochemical characterization of plant extracts, quantitative nuclear
magnetic resonance (qNMR) represents a new and powerful technique. In this ambit,
the present study was aimed at the development of a new, simple, and efficient
qNMR method for the metabolite fingerprinting of bioactive compounds in hop
cones, taking advantage of the novel ERETIC 2 tool. To the best of our knowledge,
this is the first attempt to apply this method to complex matrices of natural
origin, such as hop extracts. The qNMR method set up in this study was applied to
the quantification of both prenylflavonoids and bitter acids in eight hop
cultivars. The performance of this analytical method was compared with that of
HPLC-UV/DAD, which represents the most frequently used technique in the field of
natural product analysis. The quantitative data obtained for hop samples by means
of the two aforementioned techniques highlighted that the amount of bioactive
compounds was slightly higher when qNMR was applied, although the order of
magnitude of the values was the same. The accuracy of qNMR was comparable to that
of the chromatographic method, thus proving to be a reliable tool for the
analysis of these secondary metabolites in hop extracts. Graphical abstract
Graphical abstract related to the extraction and analytical methods applied in
this work for the analysis of bioactive compounds in Humulus lupulus L. (hop)
cones.
PMID- 29350256
TI - Analysis of phenolic compounds in different parts of pomegranate (Punica
granatum) fruit by HPLC-PDA-ESI/MS and evaluation of their antioxidant activity:
application to different Italian varieties.
AB - The analysis of pomegranate phenolic compounds belonging to different classes in
different fruit parts was performed by high-performance liquid chromatography
coupled with photodiode array and mass spectrometry detection. Two different
separation methods were optimized for the analysis of anthocyanins and
hydrolyzable tannins along with phenolic acids and flavonoids. Two C18 columns,
core-shell and fully porous particle stationary phases, were used. The parameters
for separation of phenolic compounds were optimized considering chromatographic
resolution and analysis time. Thirty-five phenolic compounds were found, and 28
of them were tentatively identified as belonging to four different phenolic
compound classes; namely, anthocyanins, phenolic acids, hydrolyzable tannins, and
flavonoids. Quantitative analysis was performed with a mixture of nine phenolic
compounds belonging to phenolic compound classes representative of pomegranate.
The method was then fully validated in terms of retention time precision,
expressed as the relative standard deviation, limit of detection, limit of
quantification, and linearity range. Phenolic compounds were analyzed directly in
pomegranate juice, and after solvent extraction with a mixture of water and
methanol with a small percentage of acid in peel and pulp samples. The accuracy
of the extraction method was also assessed, and satisfactory values were
obtained. Finally, the method was used to study identified analytes in
pomegranate juice, peel, and pulp of six different Italian varieties and one
international variety. Differences in phenolic compound profiles among the
different pomegranate parts were observed. Pomegranate peel samples showed a high
concentration of phenolic compounds, ellagitannins being the most abundant ones,
with respect to pulp and juice samples for each variety. With the same samples,
total phenols and antioxidant activity were evaluated through colorimetric
assays, and the results were correlated among them.
PMID- 29350257
TI - A new approach for the extraction of tetracyclines from soil matrices:
application of the microwave-extraction technique.
AB - The widespread use of tetracyclines (TCs) in animal husbandry is associated with
their constant penetration into the environment and the threat they might pose to
living organisms. While the literature data on the analysis of these substances
in such matrices as food, tissues, or wastewater are quite extensive, there are
still only a few methods presented for the determination of these compounds in
soil samples. Moreover, among the literature methods for the extraction of TCs
from soil samples, microwave-assisted solvent extraction (MAE) was used only once
and in combination with liquid chromatography with spectrophotometric detection
(LC-UV). However, according to the EU Commission Decision 2002/657/EC, the use of
LC-UV for the determination of compounds, including pharmaceuticals, in
environmental samples is not sufficient. Therefore, the development and
application of a sensitive and selective method using the MAE-SPE-LC-MS/MS(MRM)
technique for the isolation and identification of a mixture of oxytetracycline
(OTC), tetracycline (TC), and chlortetracycline (CTC) in soils is presented in
our study. The credibility of this method has been confirmed with good parameters
of validation. The optimal extraction conditions of three TCs using MAE
techniques were to conduct double extraction for 10 min each, at 60 degrees C,
using a mixture of ACN:McIlvaine buffer:0.1 M EDTA (2:1:1, v/v/v) and an
additional cleaning of the extracts by SPE. The effectiveness of the extraction
of these compounds was assessed based on two different ways (absolute recovery
from 46 to 65.1% and relative recovery from 101.1 to 109.5%). Finally, the
validated MAE-SPE-LC-MS/MS(MRM) method was used for the analysis of six samples
from agricultural areas of northern Poland. OTC and TC, at concentrations of 11.7
and 14.5 MUg kg-1 were determined in two different samples. An assessment of risk
quotients was also performed. The presented method was proven to be a useful tool
in the analysis of residues of selected TCs in the soil ecosystem. Obtained data
on the presence of these drugs in Polish soils is the first report for this
country.
PMID- 29350258
TI - Antitumor effects of radionuclide treatment using alpha-emitting meta-211At
astato-benzylguanidine in a PC12 pheochromocytoma model.
AB - PURPOSE: Therapeutic options for patients with malignant pheochromocytoma are
currently limited, and therefore new treatment approaches are being sought.
Targeted radionuclide therapy provides tumor-specific systemic treatments. The
beta-emitting radiopharmaceutical meta-131I-iodo-benzylguanidine (131I-MIBG)
provides limited survival benefits and has adverse effects. A new generation of
radionuclides for therapy using alpha-particles including meta-211At-astato
benzylguanidine (211At-MABG) are expected to have strong therapeutic effects with
minimal side effects. However, this possibility has not been evaluated in an
animal model of pheochromocytoma. We aimed to evaluate the therapeutic effects of
the alpha-emitter 211At-MABG in a pheochromocytoma model. METHODS: We evaluated
tumor volume-reducing effects of 211At-MABG using rat pheochromocytoma cell line
PC12 tumor-bearing mice. PC12 tumor-bearing mice received intravenous injections
of 211At-MABG (0.28, 0.56, 1.11, 1.85, 3.70 and 5.55 MBq; five mice per group).
Tumor volumes were evaluated for 8 weeks after 211At-MABG administration. The
control group of ten mice received phosphate-buffered saline. RESULTS: The 211At
MABG-treated mice showed significantly lower relative tumor growth during the
first 38 days than the control mice. The relative tumor volumes on day 21 were
509.2% +/- 169.1% in the control mice and 9.6% +/- 5.5% in the mice receiving
0.56 MBq (p < 0.01). In addition, the mice treated with 0.28, 0.56 and 1.11 MBq
of 211At-MABG showed only a temporary weight reduction, with recovery in weight
by day 10. CONCLUSION: 211At-MABG exhibited a strong tumor volume-reducing effect
in a mouse model of pheochromocytoma without weight reduction. Therefore, 211At
MABG might be an effective therapeutic agent for the treatment of malignant
pheochromocytoma.
PMID- 29350259
TI - Diminished expression of beta2-GPI is associated with a reduced ability to
mitigate complement activation in anti-GPIIb/IIIa-mediated immune
thrombocytopenia.
AB - Anti-GPIIb/IIIa-mediated complement activation has been reported to be important
in the pathogenesis of immune thrombocytopenia (ITP). However, the role of the
complement system and the involved regulatory mechanism remain equivocal. Beta2
glycoprotein I (beta2-GPI), known as the main target for antiphospholipid
autoantibodies, has been demonstrated as a complement regulator. Here, we
investigated the complement-regulatory role of beta2-GPI in anti-GPIIb/IIIa
mediated ITP. Plasma complement activation and enhanced complement activation
capacity (CAC) were found in ITP patients with anti-GPIIb/IIIa antibodies in vivo
and in vitro. Diminished plasma levels of beta2-GPI were shown in patients of
this group, which was inversely correlated with C5b-9 deposition. C5b-9
generation was inhibited by approximate physiological concentrations of beta2
GPI, in a dose-dependent manner. Inhibition of C3a generation by beta2-GPI and
the existence of beta2-GPI/C3 complexes in plasma indicated a regulation on the
level of the C3 convertase. Furthermore, beta2-GPI down-regulated the
phosphorylation levels of c-Jun N-terminal kinase (JNK) and cleavage of BH3
interacting domain death agonist (Bid) and ultimately harbored platelet lysis.
Our findings may provide a novel link between diminished plasma levels of beta2
GPI and enhanced complement activation, indicating beta2-GPI as a potential
diagnostic biomarker and therapeutic target in the treatment of anti-GPIIb/IIIa
mediated ITP.
PMID- 29350260
TI - Modulation rate transfer functions from four species of stranded odontocete
(Stenella longirostris, Feresa attenuata, Globicephala melas, and Mesoplodon
densirostris).
AB - Odontocete marine mammals explore the environment by rapidly producing
echolocation signals and receiving the corresponding echoes, which likewise
return at very rapid rates. Thus, it is important that the auditory system has a
high temporal resolution to effectively process and extract relevant information
from click echoes. This study used auditory evoked potential methods to
investigate auditory temporal resolution of individuals from four different
odontocete species, including a spinner dolphin (Stenella longirostris), pygmy
killer whale (Feresa attenuata), long-finned pilot whale (Globicephala melas),
and Blainville's beaked whale (Mesoplodon densirostris). Each individual had
previously stranded and was undergoing rehabilitation. Auditory Brainstem
Responses (ABRs) were elicited via acoustic stimuli consisting of a train of
broadband tone pulses presented at rates between 300 and 2000 Hz. Similar to
other studied species, modulation rate transfer functions (MRTFs) of the studied
individuals followed the shape of a low-pass filter, with the ability to process
acoustic stimuli at presentation rates up to and exceeding 1250 Hz. Auditory
integration times estimated from the bandwidths of the MRTFs ranged between 250
and 333 us. The results support the hypothesis that high temporal resolution is
conserved throughout the diverse range of odontocete species.
PMID- 29350261
TI - Publication rates of the abstracts presented at the annual meeting of
International Society for Pediatric Neurosurgery.
AB - INTRODUCTION: Publication of a study is the end point of the process to
contribute to the literature and confirm the scientific value of the study.
Publication rates of the abstracts presented at the annual meetings of
neurosurgery have been studied, previously. However, publication rates of the
abstracts presented at the annual meetings of pediatric neurosurgery have not
been reported, yet. We evaluated abstracts presented at the 38th annual meeting
of the International Society for Pediatric Neurosurgery (ISPN) held in South
Korea, 2010. METHODS: We conducted this cross-sectional study by reviewing the
abstracts presented at the annual meeting of the ISPN, 2010. Titles and authors
of the abstracts were surveyed using Google Scholar and PubMed/MEDLINE. Time to
publication, origin of the study, journal name in which the study has been
accepted and published, and type of study has been analyzed for each abstract.
RESULTS: The abstract booklet included 235 abstracts, consisted of 128 oral
presentations (54%) and 107 electronic posters (46%). Fifty-nine (46%) of the
oral presentations were published in a peer-reviewed journal. Laboratory studies
were more likely to be published when compared to the clinical studies (72 vs.
39%). Thirty-two (30%) of the electronic posters were published in peer-reviewed
journals. Most of the published abstracts were from Asia and Europe. Most of the
abstracts were published in Child's Nervous System and Journal of Neurosurgery:
Pediatrics. CONCLUSION: Publication rates of the abstracts presented at annual
meeting of the ISPN were comparable to the other similar congresses. Oral
presentations were more likely to be published. High publication rates of the
abstracts presented at the annual meeting of the ISPN suggested that the meeting
had a high scientific value.
PMID- 29350262
TI - Vagal nerve stimulation for medically refractory epilepsy in Angelman syndrome: a
series of three cases.
AB - BACKGROUND: We describe three children with Angelman syndrome and medically
refractory epilepsy. METHODS: Case series of three pediatric patients with
Angelman syndrome and medically refractory epilepsy. All three patients failed
medical treatment and were recommended for vagal nerve stimulator (VNS)
implantation. RESULTS: Following VNS implantation, all three patients experienced
reduction in seizure frequency greater than that afforded by medication alone.
CONCLUSION: We present vagal nerve stimulator implantation as a viable treatment
option for medically refractory epilepsy associated with Angelman syndrome.
PMID- 29350263
TI - Histological findings after argon plasma coagulation: an ex-vivo study revealing
a possible role in superficial ablative treatment of the skin.
AB - Argon plasma coagulation (APC) is an electrosurgical technique which can be used
to ablate skin lesions with limited invasion depth into dermal tissue. Hence, APC
might be well suited for the removal of epithelial tumours. However, there are no
data on the effects of APC on human skin tissue. Thus, the aim of this study was
to determine the extent of epidermal and dermal damage after APC of human skin.
We performed APC ex-vivo on 91 freshly resected human skin samples, which were
obtained after reconstructive surgical closures in actinically damaged areas.
Tissue effects were evaluated histologically and compared across different power
settings. Using 15, 30, and 45 W, median (interquartile range; IQR) coagulation
depths were 110.0 um (91.7-130.0), 113.3 um (85.8-135.0), and 130.0 um (100.0
153.3.0), respectively. Median (IQR) thickness of necrosis zone was 30.0 um (23.3
40.0) at 15 W, 26.7 um (20.0-41.6) at 30 W, and 43.3 um (30.8-57.5) at 45 W. The
Kruskal-Wallis test showed significant differences between 15 and 30 W versus 45
W for coagulation depth (P = 0.0414), necrosis zone (P = 0.0017), and necrosis
according to overlaying epidermal thickness (P = 0.0467). In summary, APC is a
simple and controllable electrosurgical technique to remove epidermal tissue with
limited penetration to the dermis. Thus, APC is particularly suited for the
ablation of epithelial skin lesions and, therefore, may serve as possible
treatment approach for intraepithelial neoplasms such as actinic keratosis.
PMID- 29350265
TI - Effects of exercise-based interventions in severe mental illness: a feasibility
study.
PMID- 29350264
TI - Linking muscle metabolism and functional variation to field swimming performance
in bluegill sunfish (Lepomis macrochirus).
AB - Skeletal muscle has diverse mechanical roles during locomotion. In swimming fish,
power-producing muscles work in concert with the accessory muscles of the fins
which augment and control power transfer to the water. Although fin muscles
represent a significant proportion of the locomotor muscle mass, their
physiological properties are poorly characterized. To examine the relationship
between muscle metabolism and the differing mechanical demands placed on distinct
muscle groups, we quantified the aerobic and glycolytic capacities of the
myotomal, pectoral and caudal muscles of bluegill sunfish. These were indicated
by the activities of citrate synthase and lactate dehydrogenase, rate-limiting
enzymes for aerobic respiration and glycolysis, respectively. The well
established roles of slow and fast myotomal muscle types in sustained and
transient propulsive movements allows their use as benchmarks to which other
muscles can be compared to assess their function. Slow myotomal muscle had the
highest CS activity, consistent with meeting the high metabolic and mechanical
power demands of body-caudal fin (BCF) swimming at the upper end of the
aerobically supported speed range. The largest pectoral adductors and abductors
had CS activities lower than the slow myotomal muscle, in line with their role
supplying thrust for low-speed, low-power swimming. The metabolic capacities of
the caudal muscles were surprisingly low and inconsistent with their activity
during steady-state BCF swimming at high speeds. This may reflect adaptation to
the observed swimming behavior in the field, which typically involved short bouts
of BCF-propulsive cycles rather than sustained propulsive activity.
PMID- 29350266
TI - Normative measurements of inferior oblique muscle thickness in Japanese by
magnetic resonance imaging using a new technique.
AB - PURPOSE: To measure the thickness of the inferior oblique muscle (IOM) among
Japanese by magnetic resonance imaging (MRI) using a new technique. METHODS: This
retrospective observational study included 78 patients (36 males and 42 females)
who underwent MRI for detection of a unilateral orbital lesion or examining
causes of unilateral retrobulbar pain. The thickness of the IOM was measured on
the side without the orbital lesion or symptom. On the quasi-sagittal plane
through the optic nerve, the major and minor axes of the cross-section of the IOM
were measured. On the coronal plane, the maximum thickness perpendicular to the
course of the IOM was measured. All measurements were performed using the digital
caliper tool of the viewing software. RESULTS: The major and minor axes on the
quasi-sagittal plane and the maximum IOM thickness on the coronal plane were 8.00
+/- 1.83 mm, 2.98 +/- 0.55 mm, 3.04 +/- 0.55 mm respectively. There were no
significant differences in IOM thickness measurements between sexes and sides (P
> 0.050, Student's t-test). No significant correlation with the major axis (r =
0.064, P = 0.576), minor axis (r = -0.065, P = 0.573) or the maximum thickness on
the coronal plane (r = -0.099, P = 0.387) was found in relation to age (Pearson's
correlation coefficient). CONCLUSIONS: The normative IOM thickness in Japanese
was presented on MRI, which were similar among all ages irrespective of sex and
side. The new technique we used is easily applicable, and the results may serve
as a guide to detect IOM involvement in inflammatory and neoplastic conditions of
the orbit.
PMID- 29350268
TI - The epitope-mediated MMP activation assay: detection and quantification of the
activation of Mmp2 in vivo in the zebrafish embryo.
AB - Matrix remodeling is a consequence of tightly regulated matrix metalloproteinase
(MMP) activity. MMPs are synthesized as inactive precursors with auto-inhibitory
N-terminal propeptides, the proteolytic removal of which exposes the catalytic
zinc ion, rendering the protease active. The regulation of MMP activation has
been investigated primarily in tissue culture and biochemical assays that lack
important biological context. Here we present the epitope-mediated MMP activation
(EMMA) assay and use it to observe the activation of Mmp2 (gelatinase A) by
endogenous mechanisms in the intact zebrafish embryo. The hemagglutinin (HA) and
GFP-tagged reporter construct becomes activated on the surface of specific cells
and this activation is abolished by broad-spectrum inhibition of
metalloproteinase activity, consistent with existing models of gelatinase A
activation. The mechanism(s) acting on the construct are spatially restricted,
metalloproteinase-dependent and replacing the HA tag with mCherry abolishes
activation, showing that the mechanism(s) are sensitive to the structure of the N
terminal domain. The construct is activated strongly in maturing myotome
boundaries, but also intracellularly within myofibrils, consistent with reports
implicating this protease in muscle development and function. In addition to
general-purpose tools for the production of "EMMAed" MMPs and other proteins, we
have established a transgenic line of zebrafish expressing EMMAedMmp2 under
control of an inducible promoter to facilitate further investigation into the
regulation of this ubiquitous ECM-remodeling protease in vivo.
PMID- 29350270
TI - Genetic data for 26 autosomal STR markers from Brazilian population.
AB - The allelic frequency distributions and statistical forensic parameters of 26
mini short tandem repeat (mini-STR) loci in a sample of 1575 unrelated
individuals from five different Brazilian regions were obtained. All the analyzed
loci showed great diversity and were highly informative. The results were
compared with those of the US Caucasian, African American, and Hispanic
population studies. This study aimed to contribute to forensic analysis for human
identification and inference of the evidential value in familial bond tests.
PMID- 29350269
TI - Exome analysis in 34 sudden unexplained death (SUD) victims mainly identified
variants in channelopathy-associated genes.
AB - Sudden cardiac death (SCD) is one of the major causes of mortality worldwide,
mostly involving coronary artery disease in the elderly. In contrary, sudden
death events in young victims often represent the first manifestation of
undetected genetic cardiac diseases, which remained without any symptoms during
lifetime. Approximately 30% of these sudden death cases have no definite cardiac
etiology after a comprehensive medicolegal investigation and are therefore termed
as sudden unexplained death (SUD) cases. Advances in high-throughput sequencing
approaches have provided an efficient diagnostic tool to identify likely
pathogenic variants in cardiovascular disease-associated genes in otherwise
autopsy-negative SUD cases. The aim of this study was to genetically investigate
a cohort of 34 unexplained death cases by focusing on candidate genes associated
with cardiomyopathies and channelopathies. Exome analysis identified potentially
disease-causing sequence alterations in 29.4% of the 34 SUD cases. Six (17.6%)
individuals had variants with likely functional effects in the channelopathy
associated genes AKAP9, KCNE5, RYR2, and SEMA3A. Interestingly, four of these six
SUD individuals were younger than 18 years of age. Since the total SUD cohort of
this study included five children and adolescents, post-mortem molecular autopsy
screening indicates a high diagnostic yield within this age group. Molecular
genetic testing represents a valuable approach to uncover the cause of death in
some of the SUD victims; however, 70-80% of the cases still remain elusive,
emphasizing the importance of additional research to better understand the
pathological mechanisms leading to a sudden death event.
PMID- 29350267
TI - Modern work-up and extended resection in perihilar cholangiocarcinoma: the AMC
experience.
AB - AIM: Perihilar cholangiocarcinoma (PHC) is a challenging disease and requires
aggressive surgical treatment in order to achieve curation. The assessment and
work-up of patients with presumed PHC is multidisciplinary, complex and requires
extensive experience. The aim of this paper is to review current aspects of
diagnosis, preoperative work-up and extended resection in patients with PHC from
the perspective of our own institutional experience with this complex tumor.
METHODS: We provided a review of applied modalities in the diagnosis and work-up
of PHC according to current literature. All patients with presumed PHC in our
center between 2000 and 2016 were identified and described. The types of
resection, surgical techniques and outcomes were analyzed. RESULTS AND
CONCLUSION: Upcoming diagnostic modalities such as Spyglass and combinations of
serum biomarkers and molecular markers have potential to decrease the rate of
misdiagnosis of benign, inflammatory disease. Assessment of liver function with
hepatobiliary scintigraphy provides better information on the future remnant
liver (FRL) than volume alone. The selective use of staging laparoscopy is
advisable to avoid futile laparotomies. In patients requiring extended resection,
selective preoperative biliary drainage is mandatory in cholangitis and when FRL
is small (< 50%). Preoperative portal vein embolization (PVE) is used when FRL
volume is less than 40% and optionally includes the left portal vein branches to
segment 4. Associating liver partition and portal vein ligation for staged
hepatectomy (ALPPS) as alternative to PVE is not recommended in PHC. N2 positive
lymph nodes preclude long-term survival. The benefit of unconditional en bloc
resection of the portal vein bifurcation is uncertain. Along these lines, an
aggressive surgical approach encompassing extended liver resection including
segment 1, regional lymphadenectomy and conditional portal venous resection
translates into favorable long-term survival.
PMID- 29350271
TI - Development of unstable hips after treatment with the Tubingen splint: mid-term
follow-up of 83 hip joints.
AB - INTRODUCTION: Early diagnosis and treatment of hip dysplasia are widely accepted
as major factors for beneficial outcome. However, modalities for reduction and
retention as well as for imaging are currently under clinical investigation.
Local and general risk factors, e.g., breech presentation and the family's desire
to avoid in-hospital treatment are major concerns in the decision-making process
and consultation. For treatment of unstable hips in newborns the treatment with
the Tubingen splint has proven good results in recent studies. However, mid- and
long-term outcome studies are missing. We report on clinical results and X-ray
parameter of initially unstable hips after treatment with the Tubingen splint at
two time points: 12-24 and 24-48 months of age. MATERIALS AND METHODS: Included
were newborns with 83 unstable hips (type D, III, IV according to Graf) which
were successfully treated with the Tubingen splint-used as reduction splint 24 h
per day/7 days per week-until type I hips were documented by ultrasound
examination. Measurments are based on routine pelvic X-ray control at the age of
12-24 and 24-48 months. The acetabular angle was determined and according to the
Tonnis-Classification evaluated into: normal findings (< 1 s), slightly
dysplastic findings (1-2 s) and severely dysplastic findings (> 2 s). Children
with secondary hip dysplasia were not included in this series. RESULTS: In 2nd
year of life, 45 hips (54.2%; initial hip type D: 47.4%, III: 63.2%, IV: 42.9%)
of the formerly unstable hips show normal X-ray findings. Although final
ultrasound showed normal findings, at this time point 28 hips (33.7%; initial hip
type D: 34.2%, III: 31.6%, IV: 42.9%) were slightly dysplastic and 10 (12.0%%;
initial hip type D: 18.4%, III: 5.3%, IV: 14.3%) still severely dysplastic. At
the age of 24-48 months, the percentage of radiologic normal hips had increased
to 61 hips (73.5%; initial hip type D: 68.4%, III: 81.6%, IV: 57.1%), the number
of slightly (19 hips) and severely dysplastic (3 hips) hips had decreased 22.9%
(initial hip type D: 28.9%, III: 15.8%, IV: 28.6%) respectively 3.6% (initial hip
type D: 2.6%, III: 2.6%, IV: 14.3%). At this time no operative intervention was
neccessary. CONCLUSIONS: Our mid-term data show on the one hand a good
development of unstable hips after successful treatment with the Tubingen splint.
On the other hand despite successful therapy and normal ultrasound findings at
the end of treatment further imaging by X-ray are mandatory to close follow-up
and to detect those which might need surgical correction of residual dysplasia.
PMID- 29350272
TI - Endoscopic endonasal approach for trigeminal schwannomas: our experience of 39
patients in 10 years.
AB - BACKGROUND: The anatomical locations involved in trigeminal schwannomas (TSs) are
quite complex. The endoscopic endonasal approach provides a minimal damage access
corridor to both anterior and middle skull base for surgery. Given the nerve
function recovery and postoperative neurological deterioration varied in
different reports, the author demonstrates his surgery tips and the functional
outcomes under endoscopic surgery in one single institution. METHODS: A
retrospective review of patients with TSs was undertaken to assess the outcome of
endoscopic surgery from 2006 to 2016. Clinical features, imaging findings,
preoperative/postoperative neurological deficits, surgical approaches and
followed up data were collected. RESULTS: Thirty-nine patients with TSs were
included in this study. Surgical approaches include endoscopic medial
maxillectomy approach (n = 8), endoscopic endonasal-assisted sublabial
transmaxillary approach (n = 27) and endoscopic endonasal-assisted sublabial
transmaxillary combined with septectomy (n = 4). Gross total resection and sub
total resection were achieved in 27 and 10 patients, respectively. The most
common chief complaint was facial numbness, accounting for 41%, with a resolved
rate of 62.5% after treatment. Fifteen patients developed new neurologic
symptoms, including facial numbness/pain (n = 9 and 2, respectively), dry eye (n
= 3) and mastication weakness (n = 1). Eight of these patients had partial
improvement except for patients with dry eye. CONCLUSION: Endoscopic endonasal
approach represents a safe and effective surgical procedure for TSs in
pterygopalatine fossa, infratemporal fossa and even Meckel cave. Tumor resection
can be achieved by endoscope with few neurologic deficits and complications.
PMID- 29350273
TI - In response to "Calculation of indirect costs of associated with postoperative
caregiver absences after pediatric tonsil surgery".
PMID- 29350275
TI - Value of transperineal ultrasound on the observation of paravaginal support.
AB - OBJECTIVE: To explore the feasibility of three-dimensional (3D) transperineal
ultrasound on the observation of paravaginal support in nulliparous and
postpartum women. METHODS: Volume datasets were acquired in 50 nulliparous and
100 postpartum women using 3D transperineal ultrasound. Paravaginal supports were
observed by studying the vaginal cross-sectional morphology. The extent of
paravaginal support in specific level were evaluated by counting out at a 2 mm
interval in tomographic ultrasound imaging mode in all subjects. The Mann-Whitney
U test were applied to establish comparisons between the two groups. RESULTS:
Three representative manifestations of vaginal cross-sectional morphology
corresponding to different paravaginal support were presented from the dorsal
side to the caudal side, both in nulliparous women and postpartum women. The
extent of paravaginal support in middle vagina was 11 slices (range 9-12) in
nulliparous women and 7 slices (range 4-10) in postpartum women (P < 0.05).
CONCLUSION: This pilot study confirmed that it was feasible to indirectly study
paravaginal support by observing the vaginal cross-sectional morphology using 3D
transperineal ultrasound.
PMID- 29350274
TI - T lymphocytes facilitate brain metastasis of breast cancer by inducing Guanylate
Binding Protein 1 expression.
AB - The discovery of genes and molecular pathways involved in the formation of brain
metastasis would direct the development of therapeutic strategies to prevent this
deadly complication of cancer. By comparing gene expression profiles of Estrogen
Receptor negative (ER-) primary breast tumors between patients who developed
metastasis to brain and to organs other than brain, we found that T lymphocytes
promote the formation of brain metastases. To functionally test the ability of T
cells to promote brain metastasis, we used an in vitro blood-brain barrier (BBB)
model. By co-culturing T lymphocytes with breast cancer cells, we confirmed that
T cells increase the ability of breast cancer cells to cross the BBB. Proteomics
analysis of the tumor cells revealed Guanylate-Binding Protein 1 (GBP1) as a key
T lymphocyte-induced protein that enables breast cancer cells to cross the BBB.
The GBP1 gene appeared to be up-regulated in breast cancer of patients who
developed brain metastasis. Silencing of GBP1 reduced the ability of breast
cancer cells to cross the in vitro BBB model. In addition, the findings were
confirmed in vivo in an immunocompetent syngeneic mouse model. Co-culturing of
ErbB2 tumor cells with activated T cells induced a significant increase in Gbp1
expression by the cancer cells. Intracardial inoculation of the co-cultured tumor
cells resulted in preferential seeding to brain. Moreover, intracerebral
outgrowth of the tumor cells was demonstrated. The findings point to a role of T
cells in the formation of brain metastases in ER- breast cancers, and provide
potential targets for intervention to prevent the development of cerebral
metastases.
PMID- 29350276
TI - Effect of swimming exercise on premenstrual syndrome.
AB - OBJECTIVE: To study the effectiveness of performing swimming on the severity of
symptoms of premenstrual syndrome (PMS). MATERIALS AND METHODS: A randomized
controlled trial that was conducted on 70 women diagnosed with PMS divided
randomly into two equal groups: Group I included women who engaged into exercise
and group II controls. Daily Symptoms Report was filled at the start and at end
of the study. RESULTS: At the posttreatment evaluation, there was a highly
significant difference between the study and control groups regarding anxiety (0
vs. 5), depression (3 vs. 12), tension (3 vs. 12), mood changes (0 vs. 7),
feeling out of control (0 vs. 7), weak coordination (0 vs. 10), confusion (2 vs.
9), headache (3 vs. 15), tiredness (4 vs. 12), pains (5 vs. 11), tenderness of
the breast (2 vs. 8), and cramps (6 vs. 17) (P < 0.001), but no such difference
was found regarding irritability, insomnia, crying, swelling, or food craving.
Regarding the percentage of symptoms changes, there was a highly significant
difference between the study and control groups regarding anxiety (- 33.3 vs. 0),
depression (- 79.29 vs. 15.56), tension (- 81.18 vs. - 6.79), mood changes (-
33.33 vs. 0), feeling out of control (- 91.67 vs. 0), weak coordination (- 100
vs. - 9.55), sleeplessness (- 71.43 vs. 0), confusion (- 84.17 vs. - 9.55),
headache (- 77.78 vs. - 6.94), fatigue (- 65.69 vs. 0), pains (- 65.83 vs. -
8.93), breast tenderness (- 87.87 vs. 4.55), cramps (- 60.77 vs. 4.55), and
swellings (- 55.05 vs. - 8.33), but no such difference was found regarding
irritability, crying, or food craving. CONCLUSIONS: There is beneficial effect of
swimming on most of the physical and psychological symptoms of PMS. CLINICAL
TRIAL REGISTRY NO: NCT03264612.
PMID- 29350278
TI - Lower body blood flow restriction training may induce remote muscle strength
adaptations in an active unrestricted arm.
AB - PURPOSE: We examined the concurrent characteristics of the remote development of
strength and cross-sectional area (CSA) of upper body skeletal muscle in response
to lower body resistance training performed with an applied blood flow
restriction (BFR). METHODS: Males allocated to an experimental BFR group (EXP; n
= 12) or a non-BFR control group (CON; n = 12) completed 7-weeks of resistance
training comprising three sets of unilateral bicep curls [50% 1-repetition
maximum (1-RM)], then four sets of bilateral knee extension and flexion exercises
(30% 1-RM). EXP performed leg exercises with an applied BFR (60% limb occlusion
pressure). 1-RM strength was measured using bilateral leg exercises and
unilateral bicep curls in both trained and untrained arms. Muscle CSA was
measured via peripheral quantitative computed tomography in the dominant leg and
both arms. RESULTS: 1-RM in the trained arm increased more in EXP (2.5 +/- 0.4
kg; mean +/- SEM) than the contralateral untrained arm (0.8 +/- 0.4 kg), and the
trained arm of CON (0.6 +/- 0.3 kg, P < 0.05). The increase in knee extension 1
RM was twofold that of CON (P < 0.01). Knee flexion 1-RM, leg CSA, and trained
arm CSA increased similarly between groups (P > 0.05), while untrained arm CSA
did not change (P > 0.05). CONCLUSION: Lower limb BFR training increased trained
arm strength more than the contralateral untrained arm, and the trained arm of
controls. However, there was no additional effect on muscle CSA. These findings
support evidence for a BFR training-derived remote strength transfer that may be
relevant to populations with localised movement disorders.
PMID- 29350279
TI - Evaluation of the convergent validity of an estimated cardiorespiratory fitness
algorithm.
AB - PURPOSE: Examine the convergent validity of a cardiorespiratory fitness (CRF)
algorithm when compared to treadmill-assessed CRF. METHODS: Data from the 1999
2004 NHANES were used (N = 3259 adults 20-49 years). Cardiorespiratory fitness
was estimated from an algorithm. Participants completed a submaximal treadmill
based protocol. We (1) evaluated the pairwise association (and ICC) between
estimated and measured cardiorespiratory fitness, (2) employed a paired samples t
test to examine potential mean differences between estimated and measured
cardiorespiratory fitness, (3) constructed a Bland-Altman plot and 95% limits of
agreement (LoA) to explore systematic differences and random error between
estimated and measured cardiorespiratory fitness, and (4) examined the
association (via linear regression) of estimated and measured cardiorespiratory
fitness with chronic disease prevalence and C-reactive protein (CRP). RESULTS:
Mean estimated CRF (10.68 METs) was lower than the mean measured CRF of 11.37
METs (p < 0.0001). The calculated pairwise correlation was of a moderate
strength, r = 0.43 (p < 0.0001), with an ICC of 0.40 (p < 0.001). Calculated LoA
indicated that estimated CRF may differ from measured CRF by 40% below to 48%
above. Regression analyses yielded statistically significant inverse associations
of estimated (unstandardized coefficient = - 0.026; p < 0.001) and measured
(unstandardized coefficient = - 0.007; p = 0.002) CRF with chronic disease and
estimated (unstandardized coefficient = - 0.08; p < 0.001) and measured
(unstandardized coefficient = - 0.03; p < 0.001) CRF with CRP. CONCLUSION:
Measured and estimated CRF were moderately correlated. However, estimated and
measured CRF were statistically significant different from one another with
noteworthy scatter around the average difference. As such, when feasible,
objective measurements of CRF should be taken.
PMID- 29350280
TI - Selective precipitation and characterization of lignin-carbohydrate complexes
(LCCs) from Eucalyptus.
AB - MAIN CONCLUSION: Six types of lignin-carbohydrate complex (LCC) fractions were
isolated from Eucalyptus. The acidic dioxane treatment applied significantly
improved the yield of LCCs. The extraction conditions had a limited impact on the
LCC structures and linkages. Characterization of the lignin-carbohydrate complex
(LCC) structures and linkages promises to offer insight on plant cell wall
chemistry. In this case, Eucalyptus LCCs were extracted by aqueous dioxane, and
then precipitated sequentially by 70% ethanol, 100% ethanol, and acidic water (pH
= 2). The composition and structure of the six LCC fractions obtained by
selective precipitation were investigated by sugar analysis, molecular weight
determination, and 2D HSQC NMR. It was found that the acidic (0.05-M HCl) dioxane
treatment significantly improved the yield of LCCs (66.4% based on Klason
lignin), which was higher than the neutral aqueous dioxane extraction, and the
extraction condition showed limited impact on the LCC structures and linkages. In
the fractionation process, the low-molecular-weight LCCs containing a high
content of carbohydrates (60.3-63.2%) were first precipitated by 70% ethanol from
the extractable solution. The phenyl glycoside (PhGlc) bonds (13.0-17.0 per
100Ar) and highly acetylated xylans were observed in the fractions recovered by
the precipitation with 100% ethanol. On the other hand, such xylan-rich LCCs
exhibited the highest frequency of beta-O-4 linkages. The benzyl ether (BE) bonds
were only detected in the fractions obtained by acidic water precipitation.
PMID- 29350282
TI - Neutrophil chemotaxis.
AB - Neutrophils are the primary cells recruited to inflamed sites during an innate
immune response to tissue damage and/or infection. They are finely sensitive to
inciting stimuli to reach in great numbers and within minutes areas of
inflammation and tissue insult. For this effective response, they can detect
extracellular chemical gradients and move towards higher concentrations, the so
called chemotaxis process or guided cell migration. This directed neutrophil
recruitment is orchestrated by chemoattractants, a chemically diverse group of
molecular guidance cues (e.g., lipids, N-formylated peptides, complement,
anaphylotoxins and chemokines). Neutrophils respond to these guidance signals in
a hierarchical manner and, based on this concept, they can be further subdivided
into two groups: "end target" and "intermediary" chemoattractants, the signals of
the former dominant over the latter. Neutrophil chemoattractants exert their
effects through interaction with heptahelical G protein-coupled receptors (GPCRs)
expressed on cell surfaces and the chemotactic response is mainly regulated by
the Rho family of GTPases. Additionally, neutrophil behavior might differ and be
affected in different complex scenarios such as disease conditions and type of
vascular bed in specific organs. Finally, there are different mechanisms to
disrupt neutrophil chemotaxis either associated to the resolution of inflammation
or to bacterial escape and systemic infection. Therefore, in the present review,
we will discuss the different molecular players involved in neutrophil
chemotaxis, paying special attention to the different chemoattractants described
and the way that they interact intra- and extravascularly for neutrophils to
properly reach the target tissue.
PMID- 29350283
TI - Epigenetic regulation of neuroblastoma development.
AB - In recent years, technological advances have enabled a detailed landscaping of
the epigenome and the mechanisms of epigenetic regulation that drive normal cell
function, development and cancer. Rather than merely a structural entity to
support genome compaction, we now look at chromatin as a very dynamic and
essential constellation that is actively participating in the tight orchestration
of transcriptional regulation as well as DNA replication and repair. The unique
feature of chromatin flexibility enabling fast switches towards more or less
restricted epigenetic cellular states is, not surprisingly, intimately connected
to cancer development and treatment resistance, and the central role of
epigenetic alterations in cancer is illustrated by the finding that up to 50% of
all mutations across cancer entities affect proteins controlling the chromatin
status. We summarize recent insights into epigenetic rewiring underlying
neuroblastoma (NB) tumor formation ranging from changes in DNA methylation
patterns and mutations in epigenetic regulators to global effects on
transcriptional regulatory circuits that involve key players in NB oncogenesis.
Insights into the disruption of the homeostatic epigenetic balance contributing
to developmental arrest of sympathetic progenitor cells and subsequent NB
oncogenesis are rapidly growing and will be exploited towards the development of
novel therapeutic strategies to increase current survival rates of patients with
high-risk NB.
PMID- 29350281
TI - An overview of methods/techniques for the detection of Cryptosporidium in food
samples.
AB - Cryptosporidium is one of the most important parasitic protozoa of concern within
the food production industry, worldwide. This review describes the evolution and
its development, and it monitors the methodology that has been used for
Cryptosporidium in food material since 1984, when the first publication appeared
regarding the detection of Cryptosporidium parvum in food materials. The methods
that are currently being used for the detection of Cryptosporidium oocysts in
food material (mainly vegetables) and all of the other available published
methods are discussed in this review. Generating more consistent and reliable
data should lead to a better understanding of the occurrence, transport and fate
of the oocysts in food material. Improvements in monitoring and developing
effective methodology, along with food security, offer more practical
possibilities for both the developed and developing worlds.
PMID- 29350284
TI - A positive relationship between spring temperature and productivity in 20
songbird species in the boreal zone.
AB - Anthropogenic climate warming has already affected the population dynamics of
numerous species and is predicted to do so also in the future. To predict the
effects of climate change, it is important to know whether productivity is linked
to temperature, and whether species' traits affect responses to climate change.
To address these objectives, we analysed monitoring data from the Finnish
constant effort site ringing scheme collected in 1987-2013 for 20 common songbird
species together with climatic data. Warm spring temperature had a positive
linear relationship with productivity across the community of 20 species
independent of species' traits (realized thermal niche or migration behaviour),
suggesting that even the warmest spring temperatures remained below the thermal
optimum for reproduction, possibly due to our boreal study area being closer to
the cold edge of all study species' distributions. The result also suggests a
lack of mismatch between the timing of breeding and peak availability of
invertebrate food of the study species. Productivity was positively related to
annual growth rates in long-distance migrants, but not in short-distance
migrants. Across the 27-year study period, temporal trends in productivity were
mostly absent. The population sizes of species with colder thermal niches had
decreasing trends, which were not related to temperature responses or temporal
trends in productivity. The positive connection between spring temperature and
productivity suggests that climate warming has potential to increase the
productivity in bird species in the boreal zone, at least in the short term.
PMID- 29350285
TI - Gut shuttle service: endozoochory of dispersal-limited soil fauna by gastropods.
AB - Numerous important ecosystem functions and services depend on soil biodiversity.
However, little is known about the mechanisms which maintain the vast belowground
biodiversity and about the filters shaping soil community composition. Yet,
biotic interactions like facilitation and dispersal by animals are assumed to
play a crucial role, particularly as most soil animal taxa are strongly limited
in their active dispersal abilities. Here, we report on a newfound interaction of
potentially high ubiquity and importance in soil communities: the endozoochorous
dispersal of soil fauna by gastropods. We focus on the dispersal-limited group of
oribatid mites, one of the most diverse and abundant soil animal groups. In a
field survey in a German riparian forest, 73% of 40 collected slugs (Arion
vulgaris) egested a total of 135 oribatid mites, belonging to 35 species.
Notably, 70% of the egested mites were alive and survived the gut passage through
slugs. Similar results were found for Roman snails (Helix pomatia), indicating
the generality of our findings across different gastropod taxa. Complementary
laboratory experiments confirmed our field observations, revealing that oribatid
mites are, indeed, ingested and egested alive by slugs, and that they are able to
independently escape the faeces and colonise new habitats. Our results strongly
indicate that gastropods may help soil organisms to disperse within habitats, to
overcome dispersal barriers, and to reach short-lived resource patches.
Gastropods might even disperse whole multi-trophic micro-ecosystems, a discovery
that could have profound implications for our understanding of dispersal
mechanisms and the distribution of soil biodiversity.
PMID- 29350286
TI - Changes of FibroScan, APRI, and FIB-4 in chronic hepatitis B patients with
significant liver histological changes receiving 3-year entecavir therapy.
AB - Noninvasive fibrosis tests have been used widely for evaluation of liver fibrosis
in patients with chronic hepatitis B (CHB). We aimed to investigate the influence
of antiviral treatment on FibroScan, APRI, and FIB-4 in CHB patients with
significant liver histological changes (SLHC) defined as inflammatory grade >= A2
and/or fibrosis stage >= F2. A total of 104 CHB patients with SLHC at the
baseline were included. FibroScan, APRI, and FIB-4 values were compared before
and after 3-year entecavir (ETV) treatment. Liver stiffness measurement values
decreased significantly after 3-year ETV treatment in cirrhosis group (from 13.6
to 9.6 kPa, p = 0.018), significant fibrosis group (from 8.4 to 5.8 kPa, p =
0.001), and mild fibrosis group (from 5.5 to 4 kPa, p < 0.001). APRI decreased
significantly after 3-year ETV treatment in patients with cirrhosis (from 0.80 to
0.25, p < 0.001), patients with significant fibrosis (from 0.54 to 0.24, p <
0.001), and those with mild fibrosis (from 0.35 to 0.23, p < 0.001). FIB-4
decreased significantly after 3-year ETV treatment in patients with cirrhosis
(from 1.27 to 0.81, p = 0.007) and significant fibrosis (from 1.12 to 0.78, p <
0.001), while did not decrease significantly in patients with mild fibrosis (from
0.90 to 0.80, p = 0.389). FibroScan, APRI, and FIB-4 values decreased
significantly after 3-year ETV treatment in CHB patients, which indicates that
these noninvasive fibrosis tests might be useful for monitoring regression of
liver fibrosis and assessing treatment efficacy during long-term ETV treatment.
PMID- 29350288
TI - Correction to: Attenuation of cortical activity triggering descending pain
inhibition in chronic low back pain patients: a functional magnetic resonance
imaging study.
AB - Inadvertently, the Fig. 7 was published incorrectly in the original publication
of the article. The correct figure should be as below.
PMID- 29350287
TI - Long non-coding RNA H19 promotes glucose metabolism and cell growth in malignant
melanoma via miR-106a-5p/E2F3 axis.
AB - PURPOSE: lncRNA H19 has been considered as an oncogenic lncRNA in many human
tumours. In the present study, we identify the role and molecular mechanism of
lncRNA H19 in melanoma. METHOD: QRT-PCR was used to detect the expression of
lncRNA H19 and E2F3 was detected in melanoma tissues. Cell counting kit-8 (CCK8),
representative metabolites analysis was used to explore the biological function
of lncRNA H19, miR-106a-5p and E2F3 in melanoma cells. Bioinformatics, luciferase
reporter assays, MS2-RIP and RNA pull-down assay was used to demonstrate the
molecular mechanism of lncRNA H19 in melanoma. We further test the function of
lncRNA H19 in vivo though Xenograft tumour assay. RESULTS: We found that lncRNA
H19 was increased in melanoma tissue, and lncRNA H19 was correlated with poor
prognosis of melanoma patients. miR-106a-5p acts as a tumour suppressor in
melanoma by targeting E2F3. E2F3 affects the melanoma cell glucose metabolism and
growth. We also demonstrated that lncRNA H19 may function as the sponge of miR
106a-5p to up-regulate E2F3 expression, and consequently promote the glucose
metabolism and growth of melanoma. CONCLUSIONS: This result elucidates a new
mechanism for lncRNA H19 in melanoma development and provides a survival
indicator and potential therapeutic target for melanoma patients.
PMID- 29350289
TI - Small RNA pathways responsible for non-cell-autonomous regulation of plant
reproduction.
AB - In angiosperms, germline precursors and germ cells are always attached to or
engulfed within somatic companion cells until just before fertilization. This is
because sperm and egg cells develop as part of the multicellular gametophyte.
Thus, the non-cell-autonomous regulation by somatic companions plays important
roles in efficient reproduction, in addition to the cell-autonomous regulation.
Epigenetic silencing of transposable elements is one of the central events by
which the germline transmits the error-free genome to the next generation. This
review focuses on small RNA-mediated epigenetic regulation of meiosis, spore
formation and pollen development. Besides microRNA (miRNA) and small interfering
RNA (siRNA), animals express PIWI-interacting RNA (piRNA), a germline-specific
class of small RNAs. Plants lack piRNA-like RNAs and, instead, express unique
classes of small RNAs: trans-acting siRNA (tasiRNA) and phased secondary siRNA
(phasiRNA). Especially in grass species, 21- and 24-nucleotide phasiRNAs are
abundant in anthers during premeiosis and meiosis. This review also describes
recent progress in reproductive phasiRNA research.
PMID- 29350291
TI - Decompressive surgery for lumbar spinal stenosis across the Atlantic: a
comparison of preoperative MRI between matched cohorts from the US and Norway.
AB - BACKGROUND: There are no uniform guidelines regarding when to operate for Lumbar
Spinal Stenosis (LSS). As we apply findings from clinical research from one
population to the next, elucidating similarities or differences provides
important context for the validity of extrapolating clinical outcomes. The aim of
this study was to compare the morphological severity of lumbar spinal stenosis on
preoperative MRI in patients undergoing decompressive surgery in Boston, USA, and
Trondheim, Norway. METHODS: In this observational retrospective study, we
compared morphological severity on MRI before surgical treatment between two
propensity score-matched patient populations with single or two-level symptomatic
LSS. We assessed the radiographic severity of LSS utilizing the Schizas
classification (grade A to D). RESULTS: Following propensity score matching,
demographics are balanced. In the Trondheim cohort, two levels decompression were
present in 36.2% of the patients vs. 41.9% in Boston, (p = 0.396). There was no
significant difference in grades A to D concerning central stenosis (p = 0.075).
When dichotomized in mild/moderate (A/B) and severe /extreme (C/D), there were no
significant differences in the rate of levels operated for high-grade stenosis
(C/D), 67.6% in the Boston group compare to 78.1% in the Trondheim group (p =
0.088). CONCLUSIONS: Trondheim, Norway, and Boston, US, have similar radiographic
thresholds of LSS for offering surgery.
PMID- 29350292
TI - Disc herniation, occult on preoperative imaging but visualized microsurgically,
as the cause of idiopathic thoracic spinal cord herniation.
AB - Idiopathic spinal cord herniation (ISCH) through an anterior dural defect is rare
and the cause is uncertain. Recently, through interpreting imaging studies, disc
herniation was proposed to be a major cause for ISCH. We describe the case of a
50-year-old woman with progressive myelopathy who was diagnosed with a thoracic
spinal cord herniation. Microsurgical exploration revealed an anterior vertical
dural defect and a small concomitant disc herniation, occult on the preoperative
imaging, which caused the dural defect and led to ISCH. This intraoperative
finding corroborates the emerging notion that disc herniation is the underlying
cause of ISCH.
PMID- 29350290
TI - The microbiology and treatment of human mastitis.
AB - Mastitis, which is generally described as an inflammation of breast tissue, is a
common and debilitating disease which frequently results in the cessation of
exclusive breastfeeding and affects up to 33% of lactating women. The condition
is a primary cause of decreased milk production and results in organoleptic and
nutritional alterations in milk quality. Recent studies employing culture
independent techniques, including metagenomic sequencing, have revealed a loss of
bacterial diversity in the microbiome of mastitic milk samples compared to
healthy milk samples. In those infected, the pathogens Staphylococcus aureus,
Staphylococcus epidermidis and members of corynebacteria have been identified as
the predominant etiological agents in acute, subacute and granulomatous mastitis,
respectively. The increased incidence of antibiotic resistance in the causative
species is also a key cause of concern for treatment of the disease, thus leading
to the need to develop novel therapies. In this respect, probiotics and
bacteriocins have revealed potential as alternative treatments.
PMID- 29350294
TI - Biocatalysis of aromatic benzyl-propionate ester by different immobilized
lipases.
AB - Benzyl propionate is an aromatic ester that possesses a fruity odor and is
usually found in nature in the composition of some fruits such as plums and
melons. This work aimed for the benzyl propionate synthesis by esterification
using a new immobilized enzyme preparation with low-cost material from Candida
antarctica (NS 88011) and three commercial immobilized lipases (Novozym 435,
Lipozyme TL-IM and Lipozyme RM-IM). Novozym 435 had the best performance even
when the solvent tert-butanol was absent of the reaction medium. Results from a
22 factorial design showed that an increase in the enzyme amount led to a higher
conversion, even when the temperature was kept at the low value. Currently, no
research had synthesized successfully benzyl propionate via esterification
mediated by lipases; and we reached an ester conversion of ~ 44% after 24 h
indicating that it is a promising route for benzyl propionate biotechnological
production.
PMID- 29350293
TI - Diversity and enzymatic potentialities of Bacillus sp. strains isolated from a
polluted freshwater ecosystem in Cuba.
AB - Genotypic and phenotypic characterization of Bacillus spp. from polluted
freshwater has been poorly addressed. The objective of this research was to
determine the diversity and enzymatic potentialities of Bacillus spp. strains
isolated from the Almendares River. Bacilli strains from a polluted river were
characterized by considering the production of extracellular enzymes using API
ZYM. 14 strains were selected and identified using 16S rRNA, gyrB and aroE genes.
Genotypic diversity of the Bacillus spp. strains was evaluated using pulsed field
gel electrophoresis. Furthermore, the presence of genetic determinants of
potential virulence toxins of the Bacillus cereus group and proteinaceous crystal
inclusions of Bacillus thuringiensis was determined. 10 strains were identified
as B. thuringiensis, two as Bacillus megaterium, one as Bacillus pumilus and one
as Bacillus subtilis. Most strains produced proteases, amylases, phosphatases,
esterases, aminopeptidases and glucanases, which reflect the abundance of
biopolymeric matter in Almendares River. Comparison of the typing results
revealed a spatio-temporal distribution among B. thuringiensis strains along the
river. The results of the present study highlight the genotypic and phenotypic
diversity of Bacillus spp. strains from a polluted river, which contributes to
the knowledge of genetic diversity of Bacilli from tropical polluted freshwater
ecosystems.
PMID- 29350295
TI - EMS-induced mutation followed by quizalofop-screening increased lipid
productivity in Chlorella sp.
AB - The objective of this study was to enhance biomass and lipid productivity in
Chlorella sp. isolate 6-4 by inducing mutagenesis with two growth inhibitors: the
herbicide quizalofop-P-ethyl, a known inhibitor of acetyl-CoA carboxylase
(ACCase) activity, and chemical mutagen, ethyl methanesulfonate (EMS), at
different concentrations and length of times. The induced-mutagenized microalgae
were screened on selective medium containing 10-100 uM quizalofop. The biomass
yield, biomass productivity, lipid content, and lipid productivity of mutagenized
microalgae were determined. The result showed that 100-200 mM EMS concentrations
and 30 min incubation time were the most effective. Biomass yield and biomass
productivity of the mutagenized microalgae E50-30-40, E100-60-40, and E100-30-60
were statistically significant higher than those of the wild type. The
mutagenized microalgae E100-30-60 showed that the highest biomass yield and
biomass productivity were 111 and 110% higher than the wild type, respectively (p
< 0.01). Lipid content and lipid productivity of the mutagenized microalgae E200
30-40 were 59 and 53% significantly higher than the wild type, respectively. It
should be noted that biomass productivity of the mutagenized microalgae E200-30
40 was not significantly different from E100-30-60, meaning that this microalga
strain exhibited highest both biomass and lipid productivity. These results
indicated that inducing mutagenesis by EMS subsequently screening by herbicide
could lead to enhance biomass and lipid accumulation. Therefore, this methodology
could be used for improvement microalgae for biofuel production.
PMID- 29350296
TI - Use of Biotechnological Devices in the Quantification of Psychophysiological
Workload of Professional Chess Players.
AB - Psychophysiological requirements of chess players are poorly understood, and
periodization of training is often made without any empirical basis. For this
reason, the aim of the present study was to investigate the psychophysiological
response and quantify the player internal load during, and after playing a chess
game. The participant was an elite 33 year-old male chess player ranked among the
300 best chess players in the world. Thus, cortical arousal by critical flicker
fusion threshold, electroencephalogram by the theta Fz/alpha Pz ratio and
autonomic modulation by heart rate variability were analyzed. Data revealed that
cortical arousal by critical flicker fusion threshold and theta Fz/alpha Pz ratio
increased and heart rate variability decreased during chess game. All these
changes indicated that internal load increased during the chess game. In
addition, pre-activation was detected in pre-game measure, suggesting that the
prefrontal cortex might be preparatory activated. For these reasons,
electroencephalogram, critical flicker fusion threshold and heart rate
variability analysis may be highly applicable tools to control and monitor
workload in chess player.
PMID- 29350297
TI - Microbial communities and their predicted metabolic functions in a desiccating
acid salt lake.
AB - The waters of Lake Magic in Western Australia are among the most geochemically
extreme on Earth. This ephemeral saline lake is characterized by pH as low as 1.6
salinity as high as 32% total dissolved solids, and unusually complex
geochemistry, including extremely high concentrations of aluminum, silica, and
iron. We examined the microbial composition and putative function in this extreme
acid brine environment by analyzing lake water, groundwater, and sediment samples
collected during the austral summer near peak evapoconcentration. Our results
reveal that the lake water metagenome, surprisingly, was comprised of mostly
eukaryote sequences, particularly fungi and to a lesser extent, green algae.
Groundwater and sediment samples were dominated by acidophilic Firmicutes, with
eukaryotic community members only detected at low abundances. The lake water
bacterial community was less diverse than that in groundwater and sediment, and
was overwhelmingly represented by a single OTU affiliated with Salinisphaera.
Pathways associated with halotolerance were found in the metagenomes, as were
genes associated with biosynthesis of protective carotenoids. During periods of
complete desiccation of the lake, we hypothesize that dormancy and entrapment in
fluid inclusions in halite crystals may increase long-term survival, leading to
the resilience of complex eukaryotes in this extreme environment.
PMID- 29350298
TI - Contribution of Mossbauer spectroscopy to the investigation of Fe/S biogenesis.
AB - Fe/S cluster biogenesis involves a complex machinery comprising several
mitochondrial and cytosolic proteins. Fe/S cluster biosynthesis is closely
intertwined with iron trafficking in the cell. Defects in Fe/S cluster
elaboration result in severe diseases such as Friedreich ataxia. Deciphering this
machinery is a challenge for the scientific community. Because iron is a key
player, 57Fe-Mossbauer spectroscopy is especially appropriate for the
characterization of Fe species and monitoring the iron distribution. This
minireview intends to illustrate how Mossbauer spectroscopy contributes to
unravel steps in Fe/S cluster biogenesis. Studies were performed on isolated
proteins that may be present in multiple protein complexes. Since a few decades,
Mossbauer spectroscopy was also performed on whole cells or on isolated
compartments such as mitochondria and vacuoles, affording an overview of the iron
trafficking. This minireview aims at presenting selected applications of 57Fe
Mossbauer spectroscopy to Fe/S cluster biogenesis.
PMID- 29350299
TI - Mutagenicity, cytotoxic and antioxidant activities of Ricinus communis different
parts.
AB - Ricinus communis (castor plant) is a potent medicinal plant, which is commonly
used in the treatment of various ailments. The present study was conducted to
appraise the cytotoxicity and mutagenicity of R. communis along with antioxidant
and antimicrobial activities. Cytotoxicity was evaluated by hemolytic and brine
shrimp assays, whereas Ames test (TA98 and TA100) was used for mutagenicity
evaluation. Plant different parts were extracted in methanol by shaking,
sonication and Soxhlet extraction methods. The R. communis methanolic extracts
showed promising antioxidant activity evaluated as through total phenolic
contents (TPC), total flavonoid content (TFC), DPPH free radical inhibition,
reducing power and inhibition of linoleic acid oxidation. R. communis seeds,
stem, leaves, fruit and root methanolic extracts showed mild to moderate
cytotoxicity against red blood cells (RBCs) of human and bovine. Brine shrimp
lethality also revealed the cytotoxic nature of extracts with LC50 in the range
of 0.22-3.70 (ug/mL) (shaking), 1.59-60.92 (ug/mL) (sonication) and 0.72-33.60
(ug/mL) (Soxhlet), whereas LC90 values were in the range of 345.42-1695.81,
660.50-14,794.40 and 641.62-15,047.80 ug/mL for shaking, sonication and Soxhlet
extraction methods, respectively. R. communis methanolic extracts revealed mild
mutagenicity against TA98 (range 1975 +/- 67 to 2628 +/- 79 revertant colonies)
and TA100 (range 2773 +/- 92 to 3461 +/- 147 revertant colonies) strains and
these values were 3267 +/- 278 and 4720 +/- 346 revertant colonies in case of
TA98 and TA100 positive controls, respectively. R. communis methanolic extracts
prevented the H2O2 and UV to Plasmid pBR322 DNA oxidative damage. Results
revealed that R. communis is a potential source of bioactive compounds and in
future studies the bioactive compounds will be identified by advanced
spectroscopic techniques.
PMID- 29350300
TI - The relationship between gait variability and cognitive functions differs between
fallers and non-fallers in MS.
AB - The objective of the study was to determine if cognitive function is associated
with step time variability in people with multiple sclerosis (PwMS). The study
included 355 PwMS (218 women), average age 41.1 (SD = 13.5), disease duration 5.9
(SD = 7.3) years, and a median expanded disability status scale score of 2.5. We
separately analyzed the sample group of fallers and non-fallers based on their
fall history. Gait variability was measured by an electronic walkway and all
participants completed a computerized cognitive test battery designed to evaluate
multiple cognitive domains. Fallers (43.7%) demonstrated elevated step time
variability (%CV), 5.0 (SD = 3.4) vs. 3.5 (SD = 1.6), P < 0.001 compared to the
non-faller subjects. According to the regression analysis in the non-fallers'
group, step time variability was found significantly associated with the global
cognitive score (P = 0.001), executive function subcategory (P = 0.038), and
motor skills subcategory (P < 0.001). No relationship between step time
variability and any cognitive domain was demonstrated in the faller group. This
study illustrated that the association between gait variability and cognition
occurs only in PwMS without a fall history. From a clinical standpoint, these
findings might help medical professionals to create improved assessment tests and
rehabilitation strategies in the MS population.
PMID- 29350301
TI - Constipation in Parkinson's Disease: a Nuisance or Nuanced Answer to the
Pathophysiological Puzzle?
AB - PURPOSE OF REVIEW: Chronic constipation is a common, nonmotor, and prodromal
symptom in Parkinson's disease (PD). Its underlying neuropathology may provide
pathophysiological insight into PD. Here, we critically review what is currently
known about the neuroanatomical and brain-gut interactions, and the origin and
progression of Lewy pathology (LP) at three levels-brain/brainstem, spinal cord,
and enteric nervous system. RECENT FINDINGS: Many recent studies have illustrated
the challenges of examining LP in tissues obtained from colon biopsies of PD
patients. Large-scale epidemiological studies have not confirmed the widely
accepted Braakpostula. In this review, we propose an alternative origin and route
of spread of LP in PD. We describe novel, noninvasive neurophysiological testing
that could advance the understanding of LP and complex bidirectional brain-pelvic
floor neural pathways in PD-a true disease model of a neurogastrointestinal
disorder. This review may provide the impetus for future studies investigating
gut and brain interaction and constipation in PD.
PMID- 29350302
TI - Antifungal mechanism of sodium dehydroacetate against Geotrichum citri-aurantii.
AB - This study investigated the potential anti-fungal mechanisms of sodium
dehydroacetate (SD) against Geotrichum citri-aurantii. The results showed that
the cell wall integrity of G. citri-aurantii was not affected, whereas the
membrane permeability of G. citri-aurantii mycelia was visibly altered by SD.
Dramatic morphological changes of the mycelia, such as loss of cytoplasm,
plasmolysis, and dissolution of intracellular substances, were observed by
scanning electron microscopy and transmission electron microscopy analyses,
indicating that the mycelium is severely damaged by the SD treatment.
Furthermore, SD apparently induced a decrease in the intracellular ATP content
before 30 min of exposure. An increase in the activity of the Na+/K+-ATPase was
also observed, indicating that Na+ ions might enter the cell and thus disturb the
energy supply. Taken together, this study's findings suggest that the anti-fungal
activity of SD against G. citri-aurantii can be attributed to the disruption of
cell membrane permeability and energy metabolism.
PMID- 29350303
TI - A Short Review of the Non-invasive Transcutaneous Pericranial Electrical
Stimulation Techniques and their Application in Headache.
AB - PURPOSE OF REVIEW: In this short review, the most common non-invasive
neuromodulatory techniques will be described, along with their advantages and
disadvantages and their application in headache. Available preventive treatments
can be unhelpful or may have unpleasant side effects; moreover, the rate of
response to preventive drugs does not exceed 50%, lower in chronic migraine;
alternative options would be welcome. Though the concept of neuromodulation was
originally developed with invasive methods, newer non-invasive techniques are
appearing. RECENT FINDINGS: The novel neuromodulatory techniques have been
developed with encouraging results: compared with traditional pharmacotherapy,
advantages of non-invasive neuromodulation include reduced incidence of adverse
effects, improved adherence, and safety and ease of use. The results are
encouraging for acute or preventive treatment of different kinds of headache. A
variety of neuromodulatory approaches is expanding fastly and has opened new
possibilities for treatment of patients suffering from many forms of headache,
especially those who have failed traditional pharmacotherapy. The non-invasive
treatments can be seen as supplementing traditional management in refractory
patients. Current study results are encouraging but preliminary and larger and
more rigorous trials are needed to clarify benefit and mode of action.
PMID- 29350304
TI - Defective mitochondrial ATPase due to rare mtDNA m.8969G>A mutation-causing
lactic acidosis, intellectual disability, and poor growth.
AB - Mutations in mitochondrial ATP synthase 6 (MT-ATP6) are a frequent cause of NARP
(neurogenic muscle weakness, ataxia, and retinitis pigmentosa) or Leigh
syndromes, especially a point mutation at nucleotide position 8993. M.8969G>A is
a rare MT-ATP6 mutation, previously reported only in three individuals, causing
multisystem disorders with mitochondrial myopathy, lactic acidosis, and
sideroblastic anemia or IgA nephropathy. We present two siblings with the
m.8969G>A mutation and a novel, substantially milder phenotype with lactic
acidosis, poor growth, and intellectual disability. Our findings expand the
phenotypic spectrum and show that mtDNA mutations should be taken account also
with milder, stable phenotypes.
PMID- 29350305
TI - Percutaneous Mechanical Circulatory Support Devices for High-Risk Percutaneous
Coronary Intervention.
AB - PURPOSE OF REVIEW: Percutaneous mechanical circulatory support devices (PMCSD)
consist of the intra-aortic balloon pump (IABP), Impella (Abiomed Inc., Danvers,
Massachusetts), Tandem Heart (Cardiac Assist, Inc., Pittsburgh, Pennsylvania), or
extracorporeal membranous oxygenation (ECMO). They augment cardiac output,
cardiac index, and cardiac power which allow the operator to mitigate hemodynamic
perturbations during high-risk percutaneous coronary intervention (HR-PCI). This
review discusses PMCSD and their contemporary literature. RECENT FINDINGS: Recent
literature has substantiated the hemodynamic benefits of PMCSD in HR-PCI and
cardiogenic shock, but no mortality benefit was found. As stent technology
improves, PCI is expanding into high-risk cases in which PMCSD provide
hemodynamic support allowing safe and complete revascularization.
PMID- 29350306
TI - Progress on the study of the mechanism of busulfan cytotoxicity.
AB - The preparation of spermatogonial stem cell (SSC) transplant recipients laid the
technical foundation for SSC transplant technology and the understanding of
spermatogenesis mechanisms. Busulfan is commonly used to prepare recipients for
mouse SSC transplantation; however, its safety and efficiency have been
questioned. This review summarizes the relationship between SSCs and Sertoli
cells (SCs), and the mechanism of busulfan toxicity against sperm cells. We
concluded that the proliferation, differentiation, and apoptosis of SSCs are
regulated by SCs. The endogenous spermatogenic cells are depleted by busulfan
treatment via alkylation of DNA, destruction of vimentin filament distribution,
disruption of SSC differentiation, promotion of SSC dormancy, and generation of
oxidative stress. However, the mechanisms require further exploration. The recent
establishment of a model in vitro culture system has provided a good technical
foundation to further explore these mechanisms, which will help us to find more
efficient methods of recipient preparation and optimal transplantation times.
PMID- 29350307
TI - Living with chronic pain: perceptions of breast cancer survivors.
AB - PURPOSE: Breast cancer treatments may lead to chronic pain. For some breast
cancer survivors (BCS), this experience can develop into the perception of living
with chronic pain. The majority of BCS are postmenopausal and have hormone
receptor-positive (HR+) breast cancer requiring aromatase inhibitors (AIs).
Neither the prevalence nor risk factors associated with the perception of living
with chronic pain among this population are well defined. METHODS: We conducted a
cross-sectional survey among postmenopausal, HR+ BCS who previously took or were
currently taking AIs. The primary outcome was patients' perception of living with
chronic pain over the past 6 months. We measured pain and demographic and
clinical variables. Multivariable logistic regression analysis was performed to
evaluate risk factors associated with the perception of chronic pain. RESULTS:
Among 1280 participants, 167 (13%) reported having the perception of living with
chronic pain before their breast cancer diagnosis; 426 (34%) reported this
perception after completion of non-hormonal cancer treatment. Seventy-eight
percent of BCSs reported experiencing at least one type of treatment-related pain
within the past 7 days, with 23% experiencing at least three types. The most
common types of pain were AI-induced musculoskeletal pain (49%) and pain at the
surgery or radiation site (31%). Younger age (< 56), BMI > 25, and the perception
of living with chronic pain before diagnosis were risk factors associated with
the perception of living with chronic pain. CONCLUSIONS: One in three
postmenopausal, HR+ BCS considered themselves to be living with chronic pain.
Effective interventions to reduce chronic pain are needed.
PMID- 29350309
TI - Population Genetics of the Endangered and Wild Edible Plant Ottelia acuminata in
Southwestern China Using Novel SSR Markers.
AB - Ottelia acuminata is an edible aquatic plant species that is endemic to
southwestern China. This plant has experienced habitat degradation resulting from
environmental change and extensive human disturbance. Determining the genetic
variation and genetic structure of O. acuminata populations could help develop
strategies to collect, evaluate, utilize and conserve the species. To this end,
we genotyped 183 individuals sampled throughout the species distribution using
twelve novel nuclear microsatellite loci (nSSRs). Eight of these nSSRs exhibited
low average levels of genetic diversity (HE = 0.351, Ho = 0.376) and showed
evidence of significant inbreeding across several populations. A high degree of
genetic differentiation was identified among populations (FST = 0.457), probably
resulting from limited pollen and seed-mediated gene flow. Only 17.8% of
variation existed between O. acuminata var. acuminata and other O. acuminata
varieties. Bayesian analysis and a UPGMA dendrogram based on Nei's genetic
distance also revealed notably low genetic differentiation among the varieties.
This low genetic differentiation is possibly attributed to shared ancestral
polymorphisms since their divergence. Additional taxonomic and phylogenetic
studies with additional molecular markers are needed to determine the population
genetic relationship between O. acuminata varieties. Conservation of this species
depends on in situ and ex situ actions, such as controlling habitat water
pollution and overexploitation and creating a germplasm bank based on the
population genetic differences. To the best of our knowledge, this study
represents the first attempt to understand the population genetics of O.
acuminata in China using novel nSSR markers developed from transcriptome
sequencing and could contribute to the conservation management of this economic
plant.
PMID- 29350308
TI - The PPARgamma agonist efatutazone delays invasive progression and induces
differentiation of ductal carcinoma in situ.
AB - PURPOSE: Ductal carcinoma in situ (DCIS) is a pre-invasive lesion of the breast
considered a precursor of invasive ductal carcinoma. This study aimed to
determine whether activated PPARgamma acts as a tumor suppressor in human DCIS
progression. METHODS: We utilized the high-affinity PPARgamma agonist,
efatutazone, to activate endogenous PPARgamma in a well-defined model for the
progression of basal (triple negative) DCIS, MCFDCIS cells, cultured under 2D and
3D conditions. We studied the effects of activated PPARgamma on DCIS progression
in MCFDCIS xenograft and C3(1)/Tag transgenic mice treated with 30 mg/kg of
efatutazone. RESULTS: In vitro, efatutazone did not alter the MCFDCIS cell
proliferation but induced phenotypic and gene expression changes, indicating that
activated PPARgamma is able to differentiate MCFDCIS cells into more luminal and
lactational-like cells. In addition, MCFDCIS tumorsphere formation in 3D was
reduced by PPARgamma activation. In vivo, efatutazone-treated MCFDCIS tumors
exhibited fat deposition along with upregulation of PPARgamma responsive genes in
both epithelial and stromal compartments, suggesting features of milk-producing
mammary epithelial cell differentiation. The efatutazone-treated lesions were
less invasive with fewer CD44+/p63+ basal progenitor cells. PPARgamma activation
downregulated Akt phosphorylation in these tumors, although the ERK pathway
remained unchanged. Similar trends in gene expression changes consistent with
lactational and luminal cell differentiation were observed in the C3(1)/Tag mouse
model after efatutazone treatment. CONCLUSIONS: Our data suggest that activation
of the PPARgamma pathway differentiates DCIS lesions and may be a useful approach
to delay DCIS progression.
PMID- 29350310
TI - Proanthocyanidins and the risk of prostate cancer in Italy.
AB - Proanthocyanidins are polymers of monomeric unit flavan-3-ols with antioxidant,
anti-inflammatory and free radical scavenging activities. We investigated the
association between proanthocyanidin intake and prostate cancer risk through data
that were collected between 1991 and 2002 in an Italian case-control study,
including a total of 1,294 incident, histologically confirmed cases of prostate
cancer and 1,451 controls admitted to hospital for acute, non-neoplastic, and non
hormone-related diseases. We estimated odds ratios (ORs) and their 95% confidence
intervals (CIs) using multiple logistic regression models, and computed energy
adjusted proanthocyanidin intakes using the residual method. The ORs for the
highest versus the lowest tertile were 0.80 (95% CI 0.83-1.00) for energy
adjusted monomers and dimers combined, 0.72 (95% CI 0.59-0.87) for polymers with
>= 3 mers, and 0.72 (95% CI 0.59-0.88) for total proanthocyanidins. The inverse
relation was stronger among cases with a Gleason score >= 7, with the ORs of 0.56
(95% CI 0.40-0.78) for monomers and dimers, 0.62 (95% CI 0.40-0.78) for polymers
with >= 3 mers, and 0.57 (95% CI 0.42-0.77) for total proanthocyanidins. These
risk estimates were consistent across strata of age, education, body mass index,
and family history of prostate cancer. Our data indicate an inverse association
between proanthocyanidins and prostate cancer risk.
PMID- 29350311
TI - Shear wave elastography and AfirmaTM gene expression classifier in thyroid
nodules with indeterminate cytology: a comparison study.
AB - PURPOSE: To compare shear wave elastography (SWE) and AfirmaTM gene expression
classifier (GEC) for diagnosis of malignancy in thyroid nodules (TNs) with
Bethesda Classification (BC) III or IV indeterminate cytology. METHODS: This
preliminary single-center prospective study was approved by the Institutional
Review Board. We evaluated 151 consented patients with 151 indeterminate TNs (123
BC III, 28 BC IV) on fine-needle aspiration biopsy (FNAB). B-mode ultrasound,
vascularity, and SWE were performed prior to FNAB. TN stiffness was measured as
shear wave velocity (SWV) in meters per second (m/s). The stiffest area of the TN
was selected for SWV measurement. GEC testing was performed with a second FNAB.
Surgery was recommended for GEC-suspicious TNs, or GEC-benign TNs with two or
more worrisome B-mode US features. RESULTS: Surgical pathology confirmed 31
malignant TNs. Among the GEC-suspicious group, 28 of 59 TNs were malignant. The
SWV value of >=3.59 m/s was the best cut-off for malignancy risk based on the
receiver operating curve (ROC). Twenty-six malignant TNs had SWV >= 3.59 m/s. The
sensitivity and specificity for SWV >= 3.59 m/s were 83.9 and 79.2%,
respectively. Positive predictive value (PPV) was 51.0% and negative predictive
value (NPV) was 95.0%. For the GEC-suspicious group, sensitivity, specificity,
PPV, and NPV were 90.3, 74.2, 47.5, and 96.7%, respectively. In multivariate
analysis, SWV and GEC-suspicious were significant predictors of malignancy, but B
mode features and vascularity were not. CONCLUSION: This preliminary study
indicates that SWE and GEC are independent predictors of malignancy in TNs with
BC III or IV.
PMID- 29350312
TI - Genesurance Counseling: Patient Perspectives.
AB - Genetic counselors (GCs) have reported an increase in discussion of insurance
related, or "genesurance," topics during genetic counseling sessions. Despite
increasing frequency, there have been no studies examining patient expectations
of GCs in these discussions. This study aimed to explore patient expectations of
GCs in these discussions, as well as examine factors that may impact
expectations. A 38-item survey was administered prior to patients receiving
prenatal or cancer genetic counseling at 11 clinic sites across UTHealth, Baylor
College of Medicine, and Sanford Health, with 360 responses analyzed. Key
variables were analyzed using descriptive statistics, chi-square analysis, and
multivariate logistic regression to assess associations between factors and
control for potential confounders. Over 75% of patients expected GCs to discuss
genesurance topics during a genetic counseling session. The majority of patients
(78%) expected GCs to provide an estimated out-of-pocket cost, know if a test is
a covered benefit (77%), and provide referral information for further questions
(76%). Two additional expectations, considered to be unrealistic in most clinical
settings, included expecting GCs to know the patient's specific insurance plan
and coverage information (57%) and provide an exact out-of-pocket cost (41%).
Ethnicity was the only significant predictor of response for these two
expectations, as African Americans and Hispanics were more likely than Caucasians
to have these beliefs. While the patient participants felt that GCs were
primarily responsible for initiating these conversations, they also reported a
personal sense of responsibility for raising questions. This study demonstrates
that patients may expect GCs to address genesurance topics in a genetic
counseling session, with specific expectations about the cost and coverage of
genetic tests. Further studies will establish the most effective way to
communicate this information to patients and examine whether and where within the
scope of GC practice, genesurance discussions fall.
PMID- 29350313
TI - Immobilization of Methylosinus trichosporium OB3b for methanol production.
AB - Due to the natural gas boom in North America, there is renewed interest in the
production of other chemical products from methane. We investigated the
feasibility of immobilizing the obligate methanotrophic bacterium Methylosinus
trichosporium OB3b in alginate beads, and selectively inactivating methanol
dehydrogenase (MDH) with cyclopropane to produce methanol. In batch cultures and
in semi-continuous flow columns, the exposure of alginate-immobilized cells to
cyclopropane or cyclopropanol resulted in the loss of the majority of MDH
activity (> 80%), allowing methanol to accumulate to significant concentrations
while retaining all of M. trichosporium OB3b's methane monooxygenase capacity.
Thereafter, the efficiency of methanol production fell due to recovery of most of
the MDH activity; however, subsequent inhibition periods resulted in renewed
methanol production efficiency, and immobilized cells retained methane-oxidizing
activity for at least 14 days.
PMID- 29350314
TI - Eimeria maricopensis n. sp. (Apicomplexa: Eimeriidae) from the Arizona cotton rat
Sigmodon arizonae Mearns (Rodentia: Cricetidae) in central Arizona, USA.
AB - Eimeria maricopensis n. sp. (Apicomplexa: Eimeriidae) is described from 2 of 15
(13%) Arizona cotton rats Sigmodon arizonae Mearns in Arizona, USA. Sporulated
oocysts of this new species are ovoidal to ellipsoidal, 20-28 * 16-22 (24.9 *
19.2) um, with a smooth, bi-layered wall; both micropyle and oocyst residuum are
absent, but fragmented polar granule material is present. Sporocysts are
ellipsoidal, 11-14 * 6-8 (12.9 * 7.0) um, with a Stieda body, sub-Stieda body,
and sporocyst residuum; sporozoites are elongate with a spheroidal anterior
refractile body and a subspheroidal posterior refractile body. In addition,
sporulated oocysts of Eimeria sigmodontis Barnard, Ernst & Dixon, 1974, Eimeria
tuskegeensis Barnard, Ernst & Dixon, 1974 and Eimeria webbae Barnard, Ernst &
Dixon, 1974 are described from S. arizonae. This is the first report on the
coccidia of S. arizonae.
PMID- 29350316
TI - Influence of Personality and Motivation on Oral Presentation Performance.
AB - Personality and motivation have been identified as influential variables
associated with foreign language learning; however, few studies have investigated
their effect on oral presentations. This study addresses the importance of both
personality and motivation in students' collaborative oral presentation
performance. A Big Five personality trait questionnaire measuring Extraversion,
Agreeableness, Conscientiousness, Neuroticism and Openness to Experience,
together with the Collaborative Inquiry-based Project Questionnaire measuring
Task, Project Work, Reinforcement, Social Learning and Social Pressure
motivational constructs were employed to evaluate 257 university students. In
general, the results showed that Extraversion, Project Work and Social Pressure
were significant correlates of oral presentation scores. The first result
suggests that extraverts possess superiority in situations where oral language
production is central to communication. This was particularly true for lower
level students, inferring that extraverted personalities can compensate for a
lower English language ability. The second indicates that the inquiry-based
nature of the assignments was an intrinsic motivator especially valued by
extraverts. The third implies that extrinsic motivation was a factor influencing
student performance. These findings extend previous research by highlighting the
contextual relationships between these affective variables and performance in
collaborative oral presentation contexts.
PMID- 29350315
TI - Revisiting embryo assisted hatching approaches: a systematic review of the
current protocols.
AB - Zona pellucida (ZP) manipulation, termed "assisted hatching" (AH), has been
introduced in order to favor embryo hatching and ultimately improve assisted
reproductive technology success but with poor proofs of safety and biological
plausibility. We herein provide a systematic review of clinical outcomes
following the application of different methods of ZP manipulation on fresh or
frozen/thawed embryos at different developmental stages in different groups of
patients. Out of the 69 papers that compared the clinical outcomes deriving from
hatched versus non-hatched embryos, only 11 considered blastocysts while the rest
referred to cleavage stage embryos. The ZP thinning of fresh embryos either by
chemical or laser approach was shown to provide very limited benefit in terms of
clinical outcomes. Better results were observed with procedures implying a higher
degree of zona manipulation, including zona removal. Studies comparing the
mechanical or chemical procedures to those laser-mediated consistently reported a
superiority of the latter ones over the former. Literature is consistent for a
benefit of ZP breaching in thawed blastocysts. This review provides the current
knowledge on the AH procedure in order to improve its efficacy in the appropriate
context. Embryologists might benefit from the approaches presented herein in
order to improve Assisted Reproduction Technologies (ART) outcomes.
PMID- 29350317
TI - A study on the role that quorum sensing play in antibiotic-resistant plasmid
conjugative transfer in Escherichia coli.
AB - Horizontal genes transfer (HGT) plays an important role in the dissemination of
antibiotic resistance genes (ARGs) in the environment. However, the mechanisms of
HGT of ARGs under the influence of antibiotics in sub-MIC remain rarely explored.
Moreover, given its collective nature, HGT was considered to be relative to
quorum sensing (QS) system. To investigate whether QS has any impact on
horizontal gene transfer of ARGs, experiments were conducted to determine the
conjugative efficiency of plasmid RP4 on Escherichia coli (E.coli) under the
influences of tetracyclines (TCs), quorum sensing autoinducers (AIs) and quorum
sensing inhibitors (QSIs). The results indicated that the sub-MIC TCs could
facilitate the conjugative transfer of RP4, a process which could be enhanced by
AIs but inhibited by QSIs. This study demonstrated the roles that QS played in
the dissemination of ARGs, and provided theoretical insights into the mechanism
of HGT of ARGs in the environment.
PMID- 29350318
TI - Father Absence, Social Networks, and Maternal Ratings of Child Health: Evidence
from the 2013 Social Networks and Health Information Survey in Mexico.
AB - Objectives To bridge the literature on the effect of father absence,
international migration, and social networks on child health, we assess the
association between father absence and maternal ratings of child poor health
(MCPH). Next we test whether social networks of immediate and extended kin
mediate the relationship between fathers' absence and MCPH. Methods Nested
logistic regression models predicting MCPH are estimated using the 2013 Social
Networks and Health Information Survey, collected in a migrant-sending community
in Guanajuato, Mexico. These unique data distinguish among father absence due to
migration versus other reasons and between immediate and extended kin ties.
Results Descriptive results indicate that 25% of children with migrant fathers
are assessed as having poor health, more often than children with present (15.5%)
or otherwise absent fathers (17.5%). In the multivariate models, fathers' absence
is not predictive of MCPH. However, the presence of extended kin ties for the
mother was associated with approximately a 50% reduction in the odds of MCPH.
Additionally, mother's poor self-assessed health was associated with increased
odds of MCPH while the presence of a co-resident adult lowered the odds of MCPH.
In sensitivity analysis among children with migrant fathers, the receipt of
paternal remittances lowered the odds of MCPH. Conclusions for Practice Social
networks have a direct and positive association with MCPH rather than mediating
the father absence-MCPH relationship. The presence of extended kin ties in the
local community is salient for more favorable child health and should be
considered in public health interventions aimed at improving child health.
PMID- 29350319
TI - Complexity of Resiliency Framework for Refugee Population: A Letter to the Editor
Regarding Wright et al. (2016).
PMID- 29350320
TI - Ethical Implications in Vaccine Pharmacotherapy for Treatment and Prevention of
Drug of Abuse Dependence.
AB - Different immunotherapeutic approaches are in the pipeline for the treatment of
drug dependence. "Drug vaccines" aim to induce the immune system to produce
antibodies that bind to drugs and prevent them from inducing rewarding effects in
the brain. Drugs of abuse currently being tested using these new approaches are
opioids, nicotine, cocaine, and methamphetamine. In human clinical trials,
"cocaine and nicotine vaccines" have been shown to induce sufficient antibody
levels while producing few side effects. Studies in humans, determining how these
vaccines interact in combination with their target drug, are underway. However,
although vaccines can become a reasonable treatment option for drugs of abuse,
there are several disadvantages that must be considered. These include i) great
individual variability in the formation of antibodies, ii) the lack of protection
against a structurally dissimilar drug that produces the same effects as the drug
of choice, and iii) the lack of an effect on the drug desire that may predispose
an addict to relapse. In addition, a comprehensive overview of several crucial
ethical issues has not yet been widely discussed in order to have not only a
biological approach to immunotherapy of addiction. Overall, immunotherapy offers
a range of possible treatment options: the pharmacological treatment of
addiction, the treatment of overdoses, the prevention of toxicity to the brain or
the heart, and the protection of the fetus during pregnancy. So far, the results
obtained from a small-scale experiment using vaccines against cocaine and
nicotine suggest that a number of important technical challenges still need to be
overcome before such vaccines can be approved for clinical use.
PMID- 29350321
TI - Sliding to predict: vision-based beating heart motion estimation by modeling
temporal interactions.
AB - PURPOSE: Technical advancements have been part of modern medical solutions as
they promote better surgical alternatives that serve to the benefit of patients.
Particularly with cardiovascular surgeries, robotic surgical systems enable
surgeons to perform delicate procedures on a beating heart, avoiding the
complications of cardiac arrest. This advantage comes with the price of having to
deal with a dynamic target which presents technical challenges for the surgical
system. In this work, we propose a solution for cardiac motion estimation.
METHODS: Our estimation approach uses a variational framework that guarantees
preservation of the complex anatomy of the heart. An advantage of our approach is
that it takes into account different disturbances, such as specular reflections
and occlusion events. This is achieved by performing a preprocessing step that
eliminates the specular highlights and a predicting step, based on a conditional
restricted Boltzmann machine, that recovers missing information caused by partial
occlusions. RESULTS: We carried out exhaustive experimentations on two datasets,
one from a phantom and the other from an in vivo procedure. The results show that
our visual approach reaches an average minima in the order of magnitude of
[Formula: see text] while preserving the heart's anatomical structure and
providing stable values for the Jacobian determinant ranging from 0.917 to 1.015.
We also show that our specular elimination approach reaches an accuracy of 99%
compared to a ground truth. In terms of prediction, our approach compared
favorably against two well-known predictors, NARX and EKF, giving the lowest
average RMSE of 0.071. CONCLUSION: Our approach avoids the risks of using
mechanical stabilizers and can also be effective for acquiring the motion of
organs other than the heart, such as the lung or other deformable objects.
PMID- 29350322
TI - Do telehealth interventions improve oral anticoagulation management? A systematic
review and meta-analysis.
AB - The benefits and harms of telehealth interventions compared to usual care for
oral anticoagulation management are unclear. A systematic review and meta
analysis was conducted to assess their impact on clinically important outcomes. A
search was conducted through MEDLINE, EMBASE and CENTRAL databases, and the
retrieved citations were independently screened and extracted by two review
authors. Cochrane Collaboration-recommended tools were used to assess for risk of
bias. Co-primary outcomes were major bleeding and major thromboembolic events. Of
2145 retrieved citations, 7 were included for qualitative synthesis (1 randomized
controlled trial, 1 prospective cohort and 5 retrospective cohorts). None
addressed direct oral anticoagulants. Telehealth interventions were mainly
consisted of telephone visits by clinicians, pharmacists and specialists. Meta
analysis of 3 studies (n = 6955) showed significant improvements in the
telehealth group for major thromboembolic events (RR 0.43, 95% CI 0.25-0.74, p =
0.002), but no significant difference for major bleeding events (RR 0.83, 95% CI
0.52-1.33, p = 0.44). There was no significant difference in any of the secondary
outcomes. The overall GRADE quality of evidence was rated very low due to high
risk of bias and low precision. Based on very low quality evidence, telehealth
interventions may lower the risk of major thromboembolic events, but not other
clinically important outcomes. A high quality study is likely to strongly
influence these results. High quality randomized trials are recommended to better
assess the benefits and harms of telehealth interventions for anticoagulation
management.
PMID- 29350323
TI - William E. Vidaver (1921-2017): an innovator, enthusiastic scientist, inspiring
teacher and a wonderful friend.
AB - William (Bill) E. Vidaver (February 2, 1921-August 31, 2017), who did his Ph.D.
with Laurence (Larry) R. Blinks at Stanford (1964) and a postdoc with C. Stacy
French (1965), taught and did research at Simon Fraser University (SFU) for
almost 30 years. Here he published over 80 papers in photosynthesis-related areas
co-authored by his graduate students, postdocs, visiting professors and SFU
colleagues. He developed a unique high-pressure cuvette for the study of oxygen
exchange and studied high-pressure effects in photosynthesis. Ulrich (Uli)
Schreiber, as a postdoctoral fellow from Germany, introduced measurements on
chlorophyll (Chl) a fluorescence to Bill's lab, leading to the discovery of
reversible inhibition of excitation energy transfer between photosynthetic
pigments and of a pivotal role of O2 in the oxidation of the electron transport
chain between Photosystem II (PS II) and PS I. Bill's and Uli's work led to a
patent of a portable chlorophyll fluorometer, the first available commercially,
which was later modified to measure whole plantlets. The latter was used in
pioneering measurement of the health of forest and crop plants undergoing in
vitro clonal micropropagation. With several other researchers (including Doug
Bruce, the late Radovan Popovic, and Sarah Swenson), he localized the quenching
site of O2 and showed a dampening effect on measurements of the four-step process
of O2 production by endogenous oxygen uptake. Bill is remembered as a hard
working but fun-loving person with a keen mind and strong sense of social
justice.
PMID- 29350324
TI - Evolving Landscape of Clinical Trials in Heart Failure: Patient Populations,
Endpoint Selection, and Regions of Enrollment.
AB - PURPOSE OF REVIEW: Clinical trial design and execution are evolving as
increasingly important considerations with respect to the success of heart
failure trials. The current review highlights temporal trends in characteristics
of heart failure clinical trials. RECENT FINDINGS: Recent trials in heart failure
have required longer recruitment phases, displayed inefficient enrollment rates,
increased use of composite and nonfatal endpoints, undergone rapid globalization,
and gradually increased focus on heart failure with preserved ejection fraction.
Understanding patterns and trends in clinical trial design and execution may
inform future planning and conduct of trials of heart failure therapeutics.
PMID- 29350325
TI - Evaluation and Management of Rotator Cuff Tears: a Primary Care Perspective.
AB - PURPOSE OF REVIEW: To provide a primary care perspective regarding the evaluation
and management of shoulder pain and rotator cuff tears. RECENT FINDINGS: In the
primary care setting, rotator cuff pathology is commonly encountered. Information
regarding the risks of oral medications for the management of the associated pain
keeps mounting. Partial-thickness rotator cuff tears remain difficult to diagnose
with a single imaging modality. Musculoskeletal education in medical schools and
non-orthopaedic residency and fellowship training programs continues to be an
area for additional improvement. In the primary care office, the initial
evaluation of shoulder pain should include a thorough musculoskeletal evaluation
in order to identify the source of the pain (e.g., shoulder, cervical spine,
chest wall), as well as the development of an initial treatment plan. Access to
imaging modalities such as ultrasound and MRI can vary depending on the resources
available in the primary care setting. The identification of patients who may
benefit from early surgical referral is imperative for optimizing outcomes.
PMID- 29350326
TI - Oxyresveratrol prevents murine H22 hepatocellular carcinoma growth and lymph node
metastasis via inhibiting tumor angiogenesis and lymphangiogenesis.
AB - The purpose of this study was to investigate the effects and mechanisms of
oxyresveratrol (Oxyres) on hepatocellular carcinoma (HCC) in vitro and in vivo.
The MTT and Transwell assays were performed to investigate the effects of Oxyres
on cell proliferation and migration of two HCC cell lines, QGY-7701 and SMMC-7721
cells. H22 cells were subcutaneously injected into hind foot pads of 70 male mice
to establish a lymph node metastasis model. These mice were randomly divided into
seven groups as follows, control group, HCC group, Oxyres 20 mg/kg group, Oxyres
40 mg/kg group, Oxyres 60 mg/kg group, Resveratrol (Res) group, and Adriamycin
(ADM) group. Oxyres, Res, and ADM were intraperitoneally injected daily for
consecutive 21 days. Tumors and popliteal lymph node were isolated and embedded
for histology analysis. Expressions of CD31 and vascular endothelial growth
factor receptor-3 (VEGFR3) in tumors were detected by immunohistocehmistry.
Expressions of vascular endothelial growth factor C (VEGF-C) were measured by
Western blot. Oxyres significantly inhibited the proliferation and migration of
QGY-7701 and SMMC-7721 cells. Oxyres significantly inhibited tumor growth (p <
0.001) and metastasis to sentinel lymph nodes (70%) in a dose-dependent manner.
Oxyres showed a similar inhibition rate as Res. Oxyres also significantly
decreased micro-blood vessel density and micro-lymphatic vessel density in tumors
(p < 0.05). Expressions of CD31, VEGFR3, and VEGF-C of tumors were also inhibited
by Oxyres (p < 0.05). Oxyres exerts anti-tumor effects against HCC through
inhibiting both angiogenesis and lymph node metastasis, which suggests Oxyres be
a potential therapeutic agent.
PMID- 29350327
TI - Hypermutated Tumors and Immune Checkpoint Inhibition.
AB - Microsatellite instability-high/DNA mismatch repair deficient tumors are found
across the cancer spectrum and often harbor markedly increased numbers of
mutations when compared to microsatellite stable/DNA mismatch repair proficient
tumors. As a result of this high mutational load, tumor-infiltrating lymphocyte
density is increased and more immunogenic neoepitopes are expressed, leading to
upregulation of immune checkpoints in these tumors. Checkpoint inhibitors such as
pembrolizumab and nivolumab, both immunoglobulin G4 (IgG4) monoclonal antibodies
that block interactions between the programmed cell death receptor-1 and its
ligands, have significant activity in this tumor class. This review will focus on
hypermutated tumors and immuno-oncology drug development for this biologically
unique tumor type, with an emphasis on FDA-approved immunotherapies for these
cancers, as well as a short discussion of the many therapeutic and scientific
challenges ahead in order to optimize the uses of this new class of drug.
PMID- 29350328
TI - Uyghur Text Matching in Graphic Images for Biomedical Semantic Analysis.
AB - How to read Uyghur text from biomedical graphic images is a challenge problem due
to the complex layout and cursive writing of Uyghur. In this paper, we propose a
system that extracts text from Uyghur biomedical images, and matches the text in
a specific lexicon for semantic analysis. The proposed system possesses following
distinctive properties: first, it is an integrated system which firstly detects
and crops the Uyghur text lines using a single fully convolutional neural
network, and then keywords in the lexicon are matched by a well-designed matching
network. Second, to train the matching network effectively an online sampling
method is applied, which generates synthetic data continually. Finally, we
propose a GPU acceleration scheme for matching network to match a complete Uyghur
text line directly rather than a single window. Experimental results on benchmark
dataset show our method achieves a good performance of F-measure 74.5%. Besides,
our system keeps high efficiency with 0.5s running time for each image due to the
GPU acceleration scheme.
PMID- 29350329
TI - Detection of human papillomavirus DNA in tumors from Rwandese breast cancer
patients.
AB - BACKGROUND: During the last decades, a great interest was given to viral etiology
of breast cancer. Indeed, due to recent technical improvements and some
encouraging new results, it has been a resurgence of interest in the possibility
that a substantial proportion of human breast cancers may be caused by viral
infections. High-risk genotypes of human papillomavirus (HPV) have been found in
breast cancer cases. In the present study, we aimed to assess the presence of HPV
DNA in breast cancer cases from Rwanda and to evaluate the association between
HPV infection and clinico-pathological features. METHODS: Therefore, a total of
47 archived formalin-fixed paraffin-embedded biopsies were collected and complete
information was recorded. HPV detection and genotyping were done by PCR
amplification and DNA sequencing. RESULTS: Overall, HPV DNA was found in 46.81%
of cases, HPV16 being the most prevalent subtype (77.27%) followed by HPV33
(13.64%) and HPV31 (9.09%). Comparison of HPV with clinico-pathological features
showed no significant difference between HPV infection and breast localization,
histological subtype, clinical stage, tumor grade, and intrinsic molecular
subtypes. CONCLUSIONS: These findings provide evidence of high prevalence of high
risk HPV in Rwandese patients with breast cancer and suggest that high-risk HPV
infections could be a risk factor associated with human breast cancer
development.
PMID- 29350330
TI - Role of dual-energy CT in the diagnosis and follow-up of gout: systematic
analysis of the literature.
AB - The aim of this systematic review was to determine the potential role of dual
energy CT in the diagnosis and follow-up of gout with regard to the Outcome
Measures in Rheumatology (OMERACT) filter. A systematic analysis of the
literature was conducted using the MEDLINE and Cochrane databases and published
abstracts of international congresses, according to the criteria of the OMERACT
filter: feasibility, reproducibility, validity versus laboratory (serum urate,
MSU synovial fluid aspirate) and other imaging modalities for gout, and its
sensitivity to change in patients on urate lowering therapy (ULT). Thirty-two
articles were found representing a total of 1502 patients. The data on
feasibility showed that the examination took little time and involved low levels
of radiation but had current limited availability. Intra- and inter-observer
reproducibility was excellent, with intra-class correlation coefficients > 0.9.
Validity in comparison with polarized-light microscopy showed good sensitivity
and specificity (> 80%). The diagnostic performance was better than that of
radiography and conventional CT-scan and at least equivalent to that of
ultrasonography. The sensitivity to change varied with effect sizes from 0.05
(low) to 1.24 (high) for decrease in the tophus volume following different ULT in
gout patients. Dual-energy CT-scan is a reproducible and accurate imaging
modality for the diagnosis of gout, particularly for tophaceous gout (intra- or
extra-articular). It can become a second-line imaging modality of choice in cases
of diagnostic doubt, such as ultrasonography. Its role remains uncertain in the
follow-up of gout patients treated with ULT and needs further clarification.
PMID- 29350331
TI - Motion deficit in nodal interphalangeal joint osteoarthritis by digital
goniometer in housewives.
AB - Range of motion (ROM) measured objectively in nodal hand osteoarthritis (NHOA) is
missing. Evaluation of collateral ligaments by ultrasound (US) is unknown in NHOA
also. To compare ROM in interphalangeal joints in housewives with nodal OA, with
a control group by a digital system using angle to voltage (Multielgon). The
second objective was to assess correlation between collateral radial and ulnar
ligaments thickness and ROM. For this cross-sectional observational study, we
assessed 60 hands with symptomatic NHOA and 30 hands of healthy housewives
matched for age. We obtained clinical and demographic characteristics (a complete
standardized physical examination of hand joints, DASH questionnaire, pain
surveys, gross grasp hand goniometer, and ROM measurements by Multielgon.
Presence of synovitis, power Doppler signal, osteophytes, and collateral
ligaments thickness was evaluated by US. We used descriptive statistics, Spearman
correlation, X2 test, t test and odds ratio. Significant less gross grasp and ROM
in the right hand were observed in NHOA (p = 0.01 for both). Presence of OA,
painful joints, disease duration, and score DASH were significant correlated with
reduced ROM (OR 4.12, 4.12, 1.04 and 1.09, respectively). Reduced ROM was
statistical significant in thumb MCP and IP joints, second and third DIP in
dominant hand. There was no association between collateral radial and ulnar
ligaments and reduced ROM. Synovitis and osteophytes were more prevalent in OA
group. Multielgon demonstrated the pattern of reduced ROM in nodal OA of
housewives particularly in MCP and IP thumb joints, second and third distal
interphalangeal joints.
PMID- 29350332
TI - Sleep in ankylosing spondylitis and non-radiographic axial spondyloarthritis:
associations with disease activity, gender and mood.
AB - The study aims were to assess the prevalence of good or poor sleep in a cohort of
axial spondyloarthritis patients and to investigate its correlation with a range
of objectively and subjectively measured variables in order to develop a model
for distinguishing good from poor sleepers. Five hundred ninety-eight patients
with ankylosing spondylitis and 61 with non-radiographic axial spondyloarthritis
completed the Jenkins Sleep Evaluation Questionnaire. Measures of disease
activity, mobility, function, mood, fatigue, quality of life, work productivity,
night-time pain and general health were gathered. Patients with ankylosing
spondylitis or non-radiographic axial spondyloarthritis were initially compared.
With the exception of waking up tired less often and having lower mobility and
functioning, the two groups were similar so were combined for subsequent
analysis. Twenty-nine percent of all patients were classified as good sleepers
and 19% as poor sleepers. Poor sleepers had higher disease activity and fatigue
scores and more night-time back pain than good sleepers. They reported poorer
quality of life, general health, mood and work-related measures. A model
incorporating mood, gender, fatigue and objective and subjective judgements of
disease activity correctly classified 87.3% of good and poor sleepers. Poor sleep
was strongly associated with poor mood, female gender, greater fatigue, greater
disease activity (specifically, spinal pain and stiffness) and better mobility;
however, the direction of causality between poor sleep and markers of active
disease was undetermined. This study also highlights the need to standardise the
measurement of sleep disturbance in axSpA to facilitate comparisons between
patient groups and interventions.
PMID- 29350333
TI - Deltoid muscle morphometry as an index of impaired skeletal muscularity in
neonatal intensive care.
AB - : We hypothesised that extremely premature infants would have decreased muscle
mass at term-corrected age compared to term-born infants and that the degree of
reduced muscle mass acquisition would correlate with the duration of invasive
mechanical ventilation. The MRI brain scans of infants admitted in the neonatal
unit at King's College Hospital between 1 January 2010 and 1 June 2016 were
retrospectively reviewed. The coronal cross-sectional area of the left deltoid
muscle (DCSA) was measured in 17 infants born < 28 weeks of gestation and in 20
infants born at term. The prematurely born infants had a median (IQR) gestation
age of 25 weeks (24-27) and the term infants 40 weeks (38-41). The duration of
invasive mechanical ventilation for the prematurely born infants was 39 days (14
62) and that for the term infants 4 days (2-5), p < 0.001. DCSA was smaller in
prematurely born infants (median 189, IQR 176-223 mm2) compared to term-born
infants (median 302, IQR 236-389 mm2), p < 0.001. DCSA was related to gestation
age (r = 0.545, p = 0.001), weight z-score at MRI (r = 0.658, p < 0.001) and days
of invasive mechanical ventilation (r = - 0.583, p < 0.001). In conclusion,
extremely premature infants studied at term had a lower muscle mass compared to
term-born infants. CONCLUSION: Our results suggest that prolonged mechanical
ventilation in infants admitted in neonatal intensive care is associated with
reduced skeletal muscle mass acquisition. What is Known: * Prolonged mechanical
ventilation in adult intensive care patients has been associated with skeletal
muscle dysfunction and atrophy. * The cross-sectional area of the deltoid muscle
has been used to evaluate muscle atrophy in infants with a previous branchial
plexus birth injury. What is New: * Premature infants studied at term exhibit
lower cross-sectional area of the deltoid muscle than their term counterparts. *
Prolonged mechanical ventilation could be associated with skeletal muscle
impairment.
PMID- 29350334
TI - The triglyceride-glucose index, an insulin resistance marker in newborns?
AB - : The study aims to assess the utility of the triglyceride-glucose index (TyG) as
a marker of insulin resistance (IR) in neonates. TyG and the homeostatic model
assessment (HOMA-IR) values were compared in 196 singleton, term normoweight and
without distress newborns. A Decision Tree procedure (CHAID) was used to classify
cases into groups or predict values of a dependent (Ln HOMA-IR) variable. Three
nodes were drawn for TyG: <= 6.7, > 6.7-7.8 and > 7.8 (p < 0.0001; F = 20.52).
The predictability of those TyG values vs HOMA-IR was statistically significant
(p < 0.0001). It was neither affected by gender (p = 0.084), glucose challenge
test (p = 0.138) classifications nor by the TyG node* glucose challenge test and
TyG node*gender interactions (p = 0.456 and p = 0.209, respectively). Glucose,
HOMA-IR, and the triglyceride/HDL cholesterol ratio increased progressively from
node 1 to 3 for TyG while QUICKI decreased. CONCLUSION: In conclusion, TyG
appears to be a suitable tool for identifying IR at birth, justifying the further
insulin determination in those neonates. TyG >= 7.8 is recommended as cut-off
point in neonates. The need for a follow-up study to confirm the TyG as early IR
marker is desirable. WHAT IS KNOWN: * HOMA-IR and the triglyceride-glucose index
(TyG) show a high correlation. * The TyG has been used as an insulin resistance
marker in adults. WHAT IS NEW: * This is the first study where TyG has been
assessed in neonates. * TyG appears to be a suitable and cheap tool for
identifying insulin resistance at birth.
PMID- 29350336
TI - Brain Over Bladder: A Systematic Review of Dual Cholinesterase Inhibitor and
Urinary Anticholinergic Use.
AB - BACKGROUND: Case reports have demonstrated that dual use of cholinesterase
inhibitors (ChIs) and urinary anticholinergics (UAChs) in older adults may be
associated with delusions, aggression, changes in cognition, and anxiety, which
typically resolve on drug discontinuation. Despite opposing mechanisms of action,
these drugs continue to be co-prescribed. OBJECTIVE: This systematic review
evaluates cognitive and functional outcomes of dual use of ChIs and UAChs and
describes its prevalence. PATIENTS AND METHODS: A literature search using terms
related to ChIs and UAChs was conducted. Observational or interventional studies
evaluating cognitive or functional outcomes in subjects receiving dual therapy
were included for the primary aim. Articles describing prevalence of dual use
were included for the secondary aim. RESULTS: Of 1340 unique results, five
studies met the inclusion criteria for the primary aim. Four of the studies
assessed cognitive outcomes-three failed to identify a significant difference in
cognitive function with dual use and the fourth study observed a statistically
significant improvement in cognition with dual use of high-dose donepezil and
solifenacin when compared with baseline. Three studies assessed functional
outcomes-one revealed a 50% greater quarterly decline in activities of daily
living (p = 0.01) among dual users functioning in the top quartile, another
revealed significant functional improvement in dual users, and the final study
did not demonstrate a significant difference. Seventeen articles were included
for the secondary aim. Prevalence of dual use ranged from 1.2 to 40.5%.
CONCLUSION: This systematic review revealed a high prevalence of dual use of ChIs
and UAChs; however, there are mixed results for cognitive and functional
outcomes. Results were limited by methodological flaws. Observational or
interventional studies assessing dual users are lacking and further study of
cognitive and functional risks of dual ChI and UACh use is needed.
PMID- 29350335
TI - Tools for Assessment of the Appropriateness of Prescribing and Association with
Patient-Related Outcomes: A Systematic Review.
AB - BACKGROUND: There are tools and criteria in the literature aimed at
distinguishing between appropriate and inappropriate medicines use. However, many
have not been externally validated with regard to patient-related outcomes,
potentially limiting their use in clinical practice. OBJECTIVES: The aim of the
study was to conduct a systematic review to summarise (1) available prescribing
appropriateness assessment tools and criteria, and (2) their associations with
patient-related outcomes (external validity). METHODS: A systematic review was
conducted using MEDLINE, EMBASE and Informit (Health Collection) databases to
screen for articles in English that examined (1) tools to assess the
appropriateness of prescribing and (2) associations of tools with patient-related
outcomes, published between 2000 and 2016, without any limits placed on the study
design, participant age or setting. RESULTS: After screening 1710 articles,
removing duplicates and shortlisting relevant articles, 42 prescribing assessment
tools were identified. Out of the 42 tools, 78.6% (n = 33) provided guidance
around stopping inappropriate medications, 28.6% (n = 12) around starting
appropriate medications, 61.9% (n = 26) were explicit (criteria based) and 31.0%
(n = 13) had been externally validated, with hospitalisation being the most
commonly used patient-related outcome (n = 9, 21.4%). CONCLUSION: The results of
this systematic review highlight the need for evidence-based and externally
validated tools, which combine the different aspects of medication management to
optimise patient-related outcomes. PROSPERO registration number: CRD42017067233.
PMID- 29350337
TI - Baseline Neurocognitive Functioning Predicts Viral Load Suppression at 1-Year
Follow-Up Among Newly Diagnosed HIV Infected Patients.
AB - The current prospective observational study evaluated the impact of baseline
neurocognitive impairment on future viral load suppression among antiretroviral
medication naive persons newly diagnosed with HIV infection. We used the Montreal
Cognitive Assessment (MoCA) score less than 26, to identify patients with
neurocognitive deficits. Of the 138 patients enrolled; virologic suppression was
seen in 61% of the participants, while 72% of the participants had a MoCA score
less than 26 at baseline. Variables significantly associated with low MoCA score
included higher age (p < 0.01) and presence of depression (p < 0.01). After
adjusting for these variables, MoCA score less than 26 was significantly
associated with a higher risk of failing achieve viral load suppression (adjusted
OR 2.7; 95% CI 1.09-6.69). Baseline neurocognitive deficit as measured by MoCA
was associated with a higher risk for failing to achieve viral load suppression
at one-year follow-up.
PMID- 29350338
TI - Reversible Suppression of Lymphoproliferation and Thrombocytopenia with Rapamycin
in a Patient with Common Variable Immunodeficiency.
PMID- 29350339
TI - Emerging Insights into the Esophageal Microbiome.
AB - PURPOSE OF REVIEW: Analysis of the esophageal microbiome remains a relatively new
field of research, and most studies to date have focused on characterizing the
esophageal microbiome in states of health and disease. Microbiome alterations
have been implicated in the pathogenesis of inflammatory and neoplastic
conditions in the colon and elsewhere in the gastrointestinal tract. The
epidemiology of various esophageal conditions including Barrett's esophagus (BE),
esophageal adenocarcinoma (EAC), esophageal squamous cell carcinoma (ESCC), and
eosinophilic esophagitis (EoE) point to the microbiome as a potential co-factor
in disease pathogenesis, and the possibility exists that these microbiome
alterations could contribute directly to the inflammatory environments necessary
for the carcinogenesis or atopy involved in these conditions. RECENT FINDINGS:
The native esophageal microbiome is similar in composition to the oral
microbiome, with a high relative abundance of the phylum Firmicutes and the genus
Streptococcus. Limited studies to date suggest that there are certain microbiome
alterations associated with esophageal diseases. Additionally, it may be possible
to indirectly assess the esophageal microbiome via non-endoscopic means. This
raises the possibility that non-invasive microbiome analysis could be used for
disease screening and monitoring. Further understanding of the role of the
esophageal microbiome in disease pathogenesis, as well as methods for microbiome
alteration, may help elucidate future targets for disease modifying therapies, or
minimally invasive screening tools in patients at high risk for development of
various esophageal conditions.
PMID- 29350340
TI - POEM in the Treatment of Esophageal Disorders.
AB - OPINION STATEMENT: PURPOSE OF THE REVIEW: Peroral endoscopic myotomy (POEM) is a
novel minimally invasive technique that has emerged as the preferred option for
the treatment of achalasia and spastic esophageal disorders (SED) at many centers
around the world. In this article, we review and summarize the recent literature
on POEM in patients with achalasia and SED. The current article is largely
focused on the new developments and findings, extended applications, and long
term outcomes of POEM in patients with achalasia and SED. RECENT FINDINGS: POEM
is a safe and effective therapy for patients with achalasia and SED. POEM is
comparable to Heller myotomy (HM) in terms of safety, efficacy, and
complications, including gastroesophageal reflux disease (GERD). Outcomes of POEM
are excellent even in patients who had prior failed therapies for achalasia,
including failed HM and prior POEM. Recent data also suggest the efficacy and
safety of POEM in both pediatric and geriatric patients. GERD after POEM is
common, and the majority of patients are asymptomatic. The management, goals of
therapy, and long-term outcomes of GERD after POEM are unclear. Objective testing
for all patients is recommended. POEM is a validated treatment for all patients
with achalasia and SED. Candidates should be carefully selected and appropriately
counseled on expected outcomes and the need for long-term surveillance.
PMID- 29350341
TI - Health, priority to the worse off, and time.
AB - It is a common view that benefits to the worse off should be given priority when
health benefits are distributed. This paper addresses how to understand who is
worse off in this context when individuals are differently well off at different
times. The paper argues that the view that this judgment about who is worse off
should be based solely on how well off individuals are when their complete lives
are considered (i.e. 'the complete lives view') is implausible in this context.
Instead, it is argued that a pluralistic stance toward this issue should be
accepted. This pluralistic stance recognizes that also the view that only focuses
on how well off individuals are now and in the future (i.e. 'the forward-looking
view') is relevant. The argument is based on appeals to intuitive judgments
concerning who is worse off in different cases and reference to various
underlying reasons why priority to benefits to the worse off is justified.
PMID- 29350342
TI - Mesenchymal stromal cells of the bone marrow and natural killer cells: cell
interactions and cross modulation.
AB - Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are multipotent
progenitor cells that have shown promise for several different therapeutic
applications. As they are able to modulate the function of several types of
immune cells, BM-MSCs are highly important in the field of cell-based
immunotherapy. Understanding BM-MSC-natural killer (NK) cell interactions is
crucial for improving their therapeutic efficiency. Here, we observed that the
type of NK cell-activating cytokine (e.g., IL-2, IL-12, IL-15 and IL-21) strongly
influenced the outcomes of their interactions with BM-MSCs. The expression
patterns of the ligands (CD112, CD155, ULPB-3) and receptors (LAIR, NCR)
mediating the cross-talk between BM-MSCs and NK cells were critically modulated
following co-culture. BM-MSCs partially impaired NK cell proliferation but up
regulated their secretion of IFN-gamma and TNF-alpha. As they are cytotoxic,
activated NK cells induced the killing of BM-MSCs. Indeed, BM-MSCs triggered the
degranulation of NK cells and increased their release of perforin and granzymes.
Interestingly, activated NK cells induced ROS generation within BM-MSCs that
caused their decreased viability and reduced expression of serpin B9.
Collectively, our observations reveal that BM-MSC-NK cell interactions may impact
the immunobiology of both cell types. The therapeutic potential of BM-MSCs will
be significantly improved once these issues are well characterized.
PMID- 29350343
TI - Syringic acid, a phenolic acid, promotes osteoblast differentiation by
stimulation of Runx2 expression and targeting of Smad7 by miR-21 in mouse
mesenchymal stem cells.
AB - Syringic acid (SA), a phenolic acid, has been used in Chinese and Indian medicine
for treating diabetes but its role in osteogenesis has not yet been investigated.
In the present study, at the molecular and cellular levels, we evaluated the
effects of SA on osteoblast differentiation. At the cellular level, there was
increased alkaline phosphatase (ALP) activity and calcium deposition by SA
treatment in mouse mesenchymal stem cells (mMSCs). At the molecular level, SA
treatment of these cells stimulated expression of Runx2, a bone transcription
factor, and of osteoblast differentiation marker genes such as ALP, type I
collagen, and osteocalcin. It is known that Smad7 is an antagonist of TGF
beta/Smad signaling and is a negative regulator of Runx2. microRNAs (miRNAs) play
a key role in the regulation of osteogenesis genes at the post-transcriptional
level and studies have reported that Smad7 is one of the target genes of miR-21.
We found that there was down regulation of Smad7 and up regulation of miR-21 in
SA-treated mMSCs. We further identified that the 3'-untranslated region (UTR) of
Smad7 was directly targeted by miR-21 in these cells. Thus, our results suggested
that SA promotes osteoblast differentiation via increased expression of Runx2 by
miR-21-mediated down regulation of Smad7. Hence, SA may have potential in
orthopedic applications.
PMID- 29350344
TI - The relationship between exercise dose and health-related quality of life with a
phase III cardiac rehabilitation program.
AB - PURPOSE: To quantify the relationship between the change in exercise dose and
health-related quality of life (HRQoL) in a cohort of patients participating in a
community-based phase-3 cardiac rehabilitation (CR) program. METHODS: A
retrospective, pre-experimental (no control group) design of 58 participants that
completed a phase-3, 12-week exercise-based CR program was used to test the
current hypothesis. Self-reported HRQoL (36-Item Short Form Health Survey Version
2, SF-36v2) was assessed prior and after completing the CR program. The change in
exercise dose was estimated from the assigned training load in weeks 1 and 12 of
the CR program. A series of regression models were fitted to ascertain the
relationship between the change in exercise dose and changes in the SF-36v2.
RESULTS: There was a strong quadratic trend between the change in exercise dose
and the mean change in SF-36 Mental and Physical Health Summary Scores. Analysis
of covariance showed that the mean changes in the SF-36 Summary Scores
statistically fluctuate across quartiles of exercise dose. The data show that
there is a threshold amount of increase in exercise (Q2; 350-510 kcal week- 1)
needed to HRQoL and that greater amounts of exercise dose (Q3; 511-687 and Q4 >=
688 kcal week- 1) did not improve HRQoL further. CONCLUSIONS: The current
findings suggest that physical and mental health-related quality of life are
improved with a phase-3 CR program. The dose-response relationship observed
indicates that a threshold exercise dose is required to improve HRQoL, and that
larger doses of exercise do not confer further improvements in HRQoL.
PMID- 29350345
TI - Measurement invariance and general population reference values of the PROMIS
Profile 29 in the UK, France, and Germany.
AB - PURPOSE: Comparability of patient-reported outcome measures over different
languages is essential to allow cross-national research. We investigate the
comparability of the PROMIS Profile 29, a generic health-related quality of life
measure, in general population samples in the UK, France, and Germany and present
general population reference values. METHODS: A web-based survey was
simultaneously conducted in the UK (n = 1509), France (1501), and Germany (1502).
Along with the PROMIS Profile 29, we collected sociodemographic information as
well as the EQ-5D. We tested measurement invariance by means of multigroup
confirmatory factor analysis (CFA). Differences in the health-related quality of
life between countries were modeled by linear regression analysis. We present
general population reference data for the included PROMIS domains utilizing
plausible value imputation and quantile regression. RESULTS: Multigroup CFA of
the PROMIS Profile 29 showed that factor means are insensitive to potential
measurement bias except in one item. We observed significant differences in
patient-reported health between countries, which could be partially explained by
the differences in overall ratings of health. The physical function and pain
interference scales showed considerable floor effects in the normal population in
all countries. CONCLUSIONS: Scores derived from the PROMIS Profile 29 are largely
comparable across the UK, France, and Germany. Due to the use of plausible value
imputation, the presented general population reference values can be compared to
data collected with other PROMIS short forms or computer-adaptive tests.
PMID- 29350346
TI - Chemical Characterization of Young Virgin Queens and Mated Egg-Laying Queens in
the Ant Cataglyphis cursor: Random Forest Classification Analysis for
Multivariate Datasets.
AB - Social insects are well known for their extremely rich chemical communication,
yet their sex pheromones remain poorly studied. In the thermophilic and
thelytokous ant, Cataglyphis cursor, we analyzed the cuticular hydrocarbon
profiles and Dufour's gland contents of queens of different age and reproductive
status (sexually immature gynes, sexually mature gynes, mated and egg-laying
queens) and of workers. Random forest classification analyses showed that the
four groups of individuals were well separated for both chemical sources, except
mature gynes that clustered with queens for cuticular hydrocarbons and with
immature gynes for Dufour's gland secretions. Analyses carried out with two
groups of females only allowed identification of candidate chemicals for queen
signal and for sexual attractant. In particular, gynes produced more undecane in
the Dufour's gland. This chemical is both the sex pheromone and the alarm
pheromone of the ant Formica lugubris. It may therefore act as sex pheromone in
C. cursor, and/or be involved in the restoration of monogyny that occurs rapidly
following colony fission. Indeed, new colonies often start with several gynes and
all but one are rapidly culled by workers, and this process likely involves
chemical signals between gynes and workers. These findings open novel
opportunities for experimental studies of inclusive mate choice and queen choice
in C. cursor.
PMID- 29350347
TI - Low birth weight is a conditioning factor for podocyte alteration and steroid
dependance in children with nephrotic syndrome.
AB - BACKGROUND: Low birth weight (LBW) is associated with reduced nephron endowment.
Clinical-pathologic features of post adaptive focal segmental glomerulosclerosis
(FSGS) have been observed in subjects with prematurity and very LBW. METHODS: We
aimed to investigate the correlation between LBW and outcome in a cohort of 89
children with idiopathic nephrotic syndrome (NS) (2-12 years-old at onset,
followed for > 3 years), of whom 21 with LBW (birth weight < 10th percentile for
gestational age, gender, ethnicity, and maternal parity or birth weight < 2500
g). RESULTS: Children with NS and LBW were found to have FSGS more frequently
than children with normal birth weight (NBW) [8/21 = 38% vs. 4/68 = 6%; odds
ratio, OR 7.754 (95% confidence interval, CI 2.184-27.525); chi2 = 9.817; p <
0.003]. Children with LBW and cortico-sensitive NS had a greater risk of cortico
dependence (CD) than those with NBW [10/13 = 76.9% vs. 28/63 = 44.4%, OR 4.744
(1.188-18.936); chi2 = 4.158; p < 0.05]. Moreover, children with LBW and CDNS
needed a greater dose of immunosuppressive drugs than those with NBW [OR 4 (1.153
13.877); chi2 = 3.842; p = 0.05]. CONCLUSIONS: LBW children developing NS had
higher risk of FSGS and CD, and needed heavier immunosuppressive therapy than
those with NBW. These data might suggest a conditioning role for hemodynamic and
podocyte changes due to reduced nephron mass in LBW.
PMID- 29350348
TI - SNF472, a novel inhibitor of vascular calcification, could be administered during
hemodialysis to attain potentially therapeutic phytate levels.
AB - BACKGROUND: Cardiovascular calcification (CVC) is a major concern in hemodialysis
(HD) and the loss of endogenous modulators of calcification seems involved in the
process. Phytate is an endogenous crystallization inhibitor and its low molecular
mass and high water solubility make it potentially dialyzable. SNF472 (the
hexasodium salt of phytate) is being developed for the treatment of calciphylaxis
and CVC in HD patients. We aimed to verify if phytate is lost during dialysis,
and evaluate SNF472's behaviour during dialysis. METHODS: Dialyzability was
assessed in vitro using online-hemodiafiltration and high-flux HD systems in
blood and saline. SNF472 was infused for 20 min and quantified at different time
points. RESULTS: Phytate completely dialyzed in 1 h at low concentrations (10
mg/l) but not when added at 30 or 66.67 mg/l SNF472. In bypass conditions,
calcium was slightly chelated during SNF472 infusion but when the system was
switched to dialysis mode the calcium in the bath compensated this chelation.
CONCLUSION: Phytate dialyses with a low clearance. The administration of SNF472
as an exogenous source of phytate allows to attain supra-physiological levels
required for its potential therapeutic properties. As SNF472 is infused during
the whole dialysis session, the low clearance would not affect the drug's
systemic exposure.
PMID- 29350349
TI - Discovery of the first macrolide antibiotic binding protein in Mycobacterium
tuberculosis: a new antibiotic resistance drug target.
PMID- 29350350
TI - Biochemical changes and clinical outcomes in 34 patients with classic
galactosemia.
AB - Impaired activity of galactose-1-phosphate uridyltransferase (GALT) causes
galactosemia, an autosomal recessive disorder of galactose metabolism. Early
initiation of a galactose-restricted diet can prevent or resolve neonatal
complications. Despite therapy, patients often experience long-term complications
including speech impairment, learning disabilities, and premature ovarian
insufficiency in females. This study evaluates clinical outcomes in 34
galactosemia patients with markedly reduced GALT activity and compares outcomes
between patients with different levels of mean galactose-1-phosphate in red blood
cells (GAL1P) using logistic regression: group 1 (n = 13) GAL1P <=1.7 mg/dL vs.
group 2 (n = 21) GAL1P >= 2 mg/dL. Acute symptoms at birth were comparable
between groups (p = 0.30) with approximately 50% of patients presenting with
jaundice, liver failure, and failure-to-thrive. However, group 2 patients had
significantly higher prevalence of negative long-term outcomes compared to group
1 patients (p = 0.01). Only one of 11 patients >3 yo in group 1 developed
neurological and severe behavioral problems of unclear etiology. In contrast, 17
of 20 patients >3 yo in group 2 presented with one or more long-term
complications associated with galactosemia. The majority of females >=15 yo in
this group also had impaired ovarian function with markedly reduced levels of
anti-Mullerian hormone. These findings suggest that galactosemia patients with
higher GAL1P levels are more likely to have negative long-term outcome.
Therefore, evaluation of GAL1P levels on a galactose-restricted diet might be
helpful in providing a prognosis for galactosemia patients with rare or novel
genotypes whose clinical presentations are not well known.
PMID- 29350352
TI - The Problem Is Not Professional Publishing, But the Publish-or-Perish Culture.
AB - The publication of scientific papers has become increasingly problematic in the
last decades. Even if we agree that a renewed model is needed for peer-reviewed
scientific publication, we think the problem does not essentially lie in
professional publishing-with economic incentives-but in the publish-or-perish
culture that dominates the lives of researchers and academics.
PMID- 29350351
TI - Convection-enhanced delivery of cetuximab conjugated iron-oxide nanoparticles for
treatment of spontaneous canine intracranial gliomas.
AB - Cetuximab conjugated iron-oxide nanoparticles (cetuximab-IONPs) have shown both
in-vitro and in-vivo anti-tumor efficacy against gliomas. The purpose of this
pilot study was to evaluate the safety and potential efficacy of cetuximab-IONPs
for treatment of spontaneously occurring intracranial gliomas in canines after
convection-enhanced delivery (CED). The use of CED allowed for direct infusion of
the cetuximab-IONPs both intratumorally and peritumorally avoiding the blood
brain barrier (BBB) and limiting systemic effects. A total of eight dogs
participated in the study and only two developed mild post-operative
complications, which resolved with medical therapy. All canines underwent a
single CED treatment of the cetuximab-IONPs over 3 days and did not receive any
further adjuvant treatments. Volumetric analysis showed a median reduction in
tumor size of 54.9% by MRI at 1-month (4-6 weeks) follow-up. Five dogs were
euthanized due to recurrence of neurological signs other than seizures, two due
to recurrent seizures, and one dog died in his sleep. Median survival time after
surgery was 248 days (mean 367 days).
PMID- 29350353
TI - Retraction and Research Integrity Education in China.
AB - This article draws the attention of research managers and policy makers to the
issue that to become a science power curtailing misconduct is the daunting
challenge that emerging countries simply cannot ignore. Systematic and
orchestrated efforts are needed to foster and institutionalize research integrity
education among all stakeholders.
PMID- 29350354
TI - Magnetic, geochemical characterization and health risk assessment of road dust in
Xuanwei and Fuyuan, China.
AB - As an accumulation of solid organic and inorganic pollutant particles on outdoor
ground surfaces, road dust is an important carrier of heavy metal contaminants
and can be a valuable medium for characterizing urban environmental quality.
Because the dusts can be an important source of atmospheric particles and take
impact on human health, the aim of this study described in detail the
mineralogical characteristics, morphology, and heavy metal content of road dust
from Xuanwei and Fuyuan, locations with high lung cancer incidence. Our results
show that the average concentrations of heavy metals in road dust were higher
than their background values. Higher concentrations of heavy metals were found in
the magnetic fractions (MFs) than in the non-magnetic fractions (NMFs). Magnetic
measurements revealed high magnetic susceptibility values in the road dust
samples, and the dominant magnetic carrier was magnetite. The magnetic grains
were predominantly pseudo-single domain, multi-domain, and coarse-grained stable
single domains (coarse SSD) in size. SEM/XRD analysis identified two groups of
magnetic particles: spherules and angular/aggregate particles. Hazard index (HI)
values for adults exposure to road dust samples, including MF, Bulk, and NMF, in
both areas were lower or close to safe levels, while HI values for childhood
exposure to magnetic fractions in both areas were very close or higher than safe
levels. Cancer risks from road dust exposure in both areas were in the acceptable
value range.
PMID- 29350355
TI - The biosorption of cadmium and cobalt and iron ions by yeast Cryptococcus
humicola at nitrogen starvation.
AB - Yeasts Cryptococcus humicola accumulated cadmium, cobalt, and iron (~ 50, 17, and
4% of the content in the medium, respectively) from the medium containing
glucose, phosphate, and 2 mmol/L of metal salts. The effects of metal absorption
on the levels of orthophosphate (Pi) and inorganic polyphosphate (polyP) varied
for the metals under study. The levels of Pi and polyP increased in the case of
cadmium and cobalt, respectively. In the case of iron, no changes in the levels
of Pi and polyP were observed. Multiple DAPI-stained polyP inclusions were
observed in the cytoplasm of cadmium-containing cells. The intensity of DAPI
staining of the cell wall especially increased in case of cobalt and iron
accumulation.
PMID- 29350359
TI - A Tribute to Dr. Shiro Miwa.
PMID- 29350358
TI - Streptomyces AcH 505 triggers production of a salicylic acid analogue in the
fungal pathogen Heterobasidion abietinum that enhances infection of Norway spruce
seedlings.
AB - The necrotrophic fungus Heterobasidion spp. is the causal agent of 'annosum root
rot' of Norway spruce. In the presence of the rhizosphere bacterium Streptomyces
AcH 505, enhanced colonization of Norway spruce roots with Heterobasidion
abietinum 331 has previously been observed. By analyzing dual cultures of H.
abietinum 331 and Streptomyces AcH 505 with HPLC, a fungal metabolite was
identified that was increased in the presence of Streptomyces AcH 505. Likewise,
challenge of H. abietum 331 with common antifungals produced by soil
streptomycetes rendered the same effect. The structure of the compound, 5
formylsalicylic acid (5-FSA), was elucidated by HPLC-HR-ESI-Orbitrap-mass
spectrometry and NMR spectroscopy. Based on in vivo measurements of maximum
photosystem II efficiency of Norway spruce seedlings, 5-FSA did not influence
plant vitality. However, when challenged with H. abietinum 331, ergosterol
amounts in infected roots increased significantly for 5-FSA pre-treated
seedlings. The severity of the infection was comparable to that observed in the
presence of Streptomyces AcH 505. 5-FSA is a structural analogue of salicylic
acid, an important signalling molecule active in plant defence. Thus, the
expression of two defence-response related marker genes (PR1, Hel) was analysed
in 5-FSA treated Arabidopsis thaliana seedlings by Northern blot analysis. The
transcription of both marker genes was altered, indicating that 5-FSA is
perceived by Arabidopsis in a similar manner to salicylic acid and is able to
interfere with Arabidopsis defence signalling. The role of 5-FSA as a potential
virulence factor of H. abietinum 331 in the presence of Streptomyces AcH 505 is
discussed.
PMID- 29350360
TI - In Memoriam Professor Shiro Miwa.
PMID- 29350361
TI - Evaluation of tourniquet application in a simulated tactical environment.
AB - BACKGROUND: Application of a tourniquet in a tactical environment is implemented
in two ways: the so-called self-aid, which is the application of a tourniquet by
the injured, and the so-called buddy aid, which is the application of a
tourniquet by the person provide aid. This study aimed to test the quality of
tourniquet use in a simulated situation, close quarter battle. METHODS: The study
involved 24 injured operators and 72 operators in the whole simulation, implying
12 sections of six individuals. To validate the application of tourniquets, the
recommendations of the Committee of Tactical Combat Care of the Injured were
used, and ultrasound with Doppler function was employed to assess the hemodynamic
effect of applying tourniquets. RESULTS: Native flow was observed in 15
operators; in three people, a trace flow was noticed, whereas in six people, a
full flow was observed. No significant difference was found between the qualities
of tourniquet application by the operators themselves compared with those of
tourniquet application by another person. The median distance of tourniquet
application from the armpit was 9.5 cm for self-aid and buddy aid. In 16
participants the outer arrangement of tourniquets was observed, and in only eight
participants tourniquets were correctly located on the internal part of the arm.
In 18 participants, tourniquets were not correctly prepared for use in the
tactical environment, whereas in only six participants, they were correctly
prepared. Most operators with a negative ultrasound flow revealed negative distal
observed pulse (DOP). Positive DOP occurred in the majority of operators with
full ultrasound flow. CONCLUSION: The application of tourniquets poses a
challenge even in case of specialized units; therefore, there is a need to
provide regular training for implementing that procedure.
PMID- 29350362
TI - Which common test should be used to assess spleen autotransplant effect?
AB - BACKGROUND: Historically, total splenectomy was the only choice of treatment for
traumatic splenic injuries. However, nonoperative management and spleen
preserving surgical techniques are preferred in modern medicine. In some
situations in which the surgeon has to perform splenectomy, spleen autotransplant
may preserve the splenic function. Selecting the best method for evaluating the
splenic autotransplant effect has been debated for several years. In this study,
we compared three common tests in evaluating the implanted spleen function.
METHODS: Participants included 10 patients who were candidates for laparotomy and
splenectomy. After performing splenectomy, we implanted five pieces of the spleen
in the greater omentum of each patient. After 3 months, the implanted spleen
function was evaluated by nuclear red blood cell (RBC) scan, serum immunoglobulin
(Ig) M level, and presence of Howell-Jolly (HJ) bodies in the peripheral blood
smear. RESULTS: All patients had normal peripheral blood smear. The IgM level was
lower than normal in one patient, and scintigraphy did not demonstrate the
transplanted spleen in another patient. CONCLUSION: All these tests may have
comparable results, but because of availability and low cost of peripheral blood
smear, which is also easily performed, it can be considered as the first option
to evaluate the implanted spleen function.
PMID- 29350363
TI - Is nighttime laparoscopic general surgery under general anesthesia safe?
AB - BACKGROUND: Fatigue and sleep deprivation can affect rational decision-making and
motor skills, which can decrease medical performance and quality of patient care.
The aim of the present study was to investigate the association between times of
the day when laparoscopic general surgery under general anesthesia was performed
and their adverse outcomes. METHODS: All laparoscopic cholecystectomies and
appendectomies performed at the emergency surgery department of a tertiary
university hospital from 01. 01. 2016 to 12. 31. 2016 were included. Operation
times were divided into three groups: 08.01-17.00 (G1: daytime), 17.01-23.00 (G2:
early after-hours), and 23.01-08.00 (G3: nighttime). The files of the included
patients were evaluated for intraoperative and postoperative surgery and
anesthesia-related complications. RESULTS: We used multiple regression analyses
of variance with the occurrence of intraoperative complications as a dependent
variable and comorbidities, age, gender, body mass index (BMI), ASA score, and
operation time group as independent variables. This revealed that nighttime
operation (p<0.001; OR, 6.7; CI, 2.6-16.9) and older age (p=0.004; OR, 1.04; CI,
1.01-1.08) were the risk factor for intraoperative complications. The same
analysis was performed for determining a risk factor for postoperative
complications, and none of the dependent variables were found to be associated
with the occurrence of postoperative complications. CONCLUSION: Nighttime surgery
and older patient age increased the risk of intraoperative complications without
serious morbidity or mortality, but no association was observed between the
independent variables and the occurrence of postoperative complications.
PMID- 29350364
TI - A retrospective analysis of 2713 hospitalized burn patients in a burns center in
Turkey.
AB - BACKGROUND: Burn trauma is a significant health problem that has physical,
psychological, and economic repercussions on affected patients. The aim of this
study was to present epidemiological and demographic characteristics of patients
treated over an 8-year period at a reference burn treatment center located in the
northeast of Turkey and serving a population of approximately four million
people. METHODS: Each patient's medical record was reviewed, and demographic
features, source of burns, place of residence, total body surface area (TBSA),
surgical treatment, duration of hospital stay, and mortality rates were analyzed.
RESULTS: The most frequent cause of burn was scalding from hot liquids (2013
cases, 74.2%). Freeze burn was observed in 16 (0.6%) cases due to climatic
conditions of the region where our burn center is located. Grouping based on TBSA
revealed that 88.7% patients had TBSA of 0%-15%, 8% patients had TBSA of 15%-30%,
and 3.3% patients had TBSA >= %30.The most common microorganism was Pseudomonas
aeruginosa. A total of 24 patients (0.9%; 8 males, 16 females) died, including 7
children and 17 adults. CONCLUSION: Removal of tandirs and replacement with high
ovens, restriction of cheese and butter production under primitive circumstances,
encouraging cheese and butter production via dairy farm systems, and raising
people's awareness through training programs could greatly reduce the number of
the burn accidents occurring in this region.
PMID- 29350365
TI - Characteristics of pediatric and adult cases with open globe injury and factors
affecting visual outcomes: A retrospective analysis of 294 cases from Turkey.
AB - BACKGROUND: This study aimed to evaluate 1-year follow-up results of cases that
were diagnosed with open globe injury (OGI), to compare trauma-related
characteristics between pediatric and adult cases, and to determine risk factors
for a poor final visual acuity. METHODS: This study enrolled 294 cases that met
the OGI definition and were followed up for at least 1 year. Demographic and
clinical features regarding ocular trauma were recorded. The cases were divided
into two groups according to age: pediatric (<=16 years) and adult (>16 years)
groups. RESULTS: Children were exposed to accidents that led to OGI mostly at
home, whereas adults were exposed to such accidents mostly in the office.
Penetrating injuries were more common in children than in adults, and injuries
most commonly occurred owing to spiky objects. Zone I injuries were most frequent
in both children and adults. The frequency of high-grade injuries increased with
age. Foreign body injuries and multiple surgeries were more common in adults than
in children. There was no difference between the two age groups based on ocular
trauma score (OTS) and visual acuity. OTS predicted the need for multiple
surgeries. In the adult group, age, multiple surgeries, and initial visual acuity
were significant risk factors for the final visual acuity that was achieved.
CONCLUSION: OGI causes and risk factors for poor final visual outcomes differ in
adults and children. The knowledge of these differences is crucial for taking
adequate preventive measures and decreasing morbidity.
PMID- 29350366
TI - Health results of a coup attempt: evaluation of all patients admitted to
hospitals in Istanbul due to injuries sustained during the July 15, 2016 coup
attempt.
AB - BACKGROUND: A coup attempt against the government took place in Turkey on July
15, 2016. This attempt caused serious injuries and deaths in the country. In this
study, the data of patients referred to all hospitals in Istanbul during the
attempt were evaluated, and differences between natural disasters, other
terrorist actions, and coup attempts were analyzed. METHODS: In total, 1104
patients were injured in the abovementioned coup attempt. In this study, the
demographic and health information of 882 coup victims who were admitted to all
hospitals (state and private) in Istanbul on July 15 and 16, 2016 and registered
at the Crisis Center of Istanbul Provincial Health Directorate was analyzed.
RESULTS: Of the 882 patients evaluated, 97.27% were male and 2.73% were female.
The mean age of the patients was 34.12 years. Most (82.43%) patients were
admitted to state hospitals, and 17.57% were admitted to private hospitals. The
total mortality rate due to the abovementioned coup attempt was 10.4% (9.76% in
state hospitals and 13.54% in private hospitals). Of the 882 patients evaluated,
65.07% had gunshot injuries, 11.11% had been assaulted, 7.70% had experienced
tank/motor vehicle accidents, 5.44% had other penetrating injuries, 5.32% had
soft-tissue trauma, 2.83% had experienced falls (including falls from heights),
0.33% had psychiatric disorders, and 2.15% were admitted for other reasons.
CONCLUSION: The patterns of injury and mortality resulting from the July 15, 2016
coup attempt differed from those resulting from natural disasters and terrorist
acts and were similar to those encountered during wars: the victims were
predominantly male, similar to those in wars. Following a coup attempt, an
increase in the number of patients with post-traumatic stress disorder can be
expected. Further studies focusing on the incidence of this disorder due to the
abovementioned coup attempt in Turkey are needed. Hospital disaster plans need to
include information and plans related to terrorist acts, such as coup attempts.
PMID- 29350367
TI - Posterior interosseous flap versus reverse adipofascial radial forearm flap for
soft tissue reconstruction of dorsal hand defects.
AB - BACKGROUND: Our objective was to compare the outcomes of dorsal hand defect
reconstruction using a posterior interosseous artery flap (PIAF) and a reverse
adipofascial radial forearm flap (RARFF). METHODS: From 2008 to 2013, 23 patients
who underwent hand soft tissue defect reconstruction with PIAF (11 patients) and
RARFF (12 patients) were included in this retrospective study. Reconstruction
methods were compared in terms of functionality with disability of the arm,
shoulder, and hand (DASH) score and range of motion (ROM) and aesthetically with
scar assessment. Operation times, length of hospital stay, and donor site
problems were compared. RESULTS: We found no statistically significant
differences between PIAF and RARFF in terms of ROM, DASH score, and length of
hospital stay. Statistically significant differences were found in operation
time, scar assessment, and donor site problems between PIAF and RARFF patients.
CONCLUSION: RARFF showed better results than PIAF in dorsal hand defects, but in
RARFF, the major arteries of the hand are sacrificed.
PMID- 29350368
TI - Clinical features, diagnosis, and treatment of traumatic pulmonary pseudocysts.
AB - BACKGROUND: Traumatic pulmonary pseudocysts (TPP) are rare complications of blunt
chest trauma. The aim of this study is to increase the understanding of this rare
entity with imaging and clinical parameters for preventing complications and
determining the correct treatment approach by observing 15 cases. METHODS: We
retrospectively reviewed the medical data and thoracic computed tomography scans
of 185 patients who underwent examinations in our department after chest trauma
between July 2014 and December 2015. RESULTS: Fifteen patients had TPPs, and
their clinical features and imaging findings were evaluated. Their average age
was 26.33 (range, 1-89) years. The cause of TPP was traffic accident in 13
patients and falling from a height in two. Tube thoracostomy was required in five
patients. None of the patients required thoracotomy, and 66% of them recovered
without any complications. Five patients died because of serious concomitant
injuries. CONCLUSION: Sudden shearing force across the pulmonary parenchyma
results in an area of pulmonary contusion and airtransfer from the airway to the
contused area, which in turn leads to pneumatocele formation. Conservative
treatment is recommended for these patients, but complications can occur because
of cyst rupture. Patients should be closely monitored and be made aware of the
risk of life-threatening complications.
PMID- 29350369
TI - Analyses of combat-related injuries to the maxillofacial and cervical regions and
experiences in an operational field hospital.
AB - BACKGROUND: With the changing conditions of war, maxillofacial injuries are
observed more frequently. Particularly in urban areas, high-energy explosive
devices (HEEDs), such as improvised explosive devices, are often used alongside
long-barreled weapons (LBWs). It is important to use trauma scoring systems and a
multidisciplinary approach for medically and accurately responding to the trauma
patient in a timely manner. This study aimed to compare the Military Combat
Injury Scale (MCIS) and Military Functional Incapacity Scale (MFIS) between
injuries sustained by LBWs or HEEDs and to share experiences of an operational
field hospital. METHODS: Medical data of 84 patients admitted to an operational
field hospital with maxillofacial and cervical injuries sustained by LBWs and
HEEDs between July 27, 2015, and July 22, 2016 were reviewed. MCIS and MFIS
scores were calculated for all patients; records of the qualifying patients were
studied for the Glasgow Coma Scale (GCS) scores and injury sites. The patients
were divided into two groups according to the device/weapon causing the injury:
injuries sustained by LBWs in group I and those sustained by HEEDs in group II.
RESULTS: All patients were males, with a mean age of 28.75 (range 20-58) years.
The average GCS score was 13.4, but it was lower than 15 in 16 (19%) of the
patients. There was no statistically significant difference in MCIS scores
between the LBW and HEED groups (p=0.206). In addition, there was no
statistically significant difference in MFIS scores between the LBW and HEED
groups (p=0.238). CONCLUSION: Maxillofacial and cervical region injuries are
increasing in modern conflicts that are usually located in urban areas. Injuries
sustained by HEEDs as well as those sustained by LBWs in the maxillofacial area
are morbid and mortal. Rapid and comprehensive intervention is life-saving and
helping the patient to further trauma treatment.
PMID- 29350370
TI - Operative and non-operative management of children with abdominal gunshot
injuries.
AB - BACKGROUND: Non-operative management (NOM) is a standard treatment method for
solid organ injuries worldwide. There is no consensus on the management of
gunshot wounds (GSW) because of the higher frequency of hollow viscus injuries
(HVI) and the unpredictable depth of tissue damage produced by kinetic energy
transfer during retardation of the bullet. Here we aimed to reevaluate
indications for surgery and NOM based on our pediatric patients with abdominal
GSW. METHODS: We performed a retrospective analysis of patients evaluated and
treated for abdominal GSW at University of Dicle between January 2010 and October
2016. Patients with hemodynamic instability, signs of peritonitis on serial
abdominal examination, and free air in the abdomen underwent laparotomy; these
were included in group I (n=17). Patients managed non-operatively were included
in group II (n=13). RESULTS: Our statistical analysis showed significantly lower
Hb levels and systolic blood pressure levels (p<0.001) and higher pulse rate,
higher mean injury severity score, and longer length of stay at intensive care
unit in patients in group I than in those in group II (p<0.001). We further
detected colon perforation (n=10) and small bowel perforation (n=7) in patients
in group I; liver laceration (n=4), splenic injury (n=1), and renal injury (n=3)
but no solid organ injury or HVI (n=5) were detected in patients in group II.
CONCLUSION: The major drawback of NOM is the difficulty in diagnosing HVI in
abdominal GSW, which may delay treatment. We suggest that patients with solid
organ damage who are hemodynamically stable and exhibit no signs of peritonitis
upon serial abdominal exam may be treated with NOM.
PMID- 29350371
TI - Fundus-first technique and partial cholecystectomy for difficult laparoscopic
cholecystectomies.
AB - BACKGROUND: This study aims to evaluate the impact of conversion from retrograde
dissection to fundus-first technique (FF) or laparoscopic partial cholecystectomy
(LPC) on complication rates, operation time, and duration of hospitalization.
METHODS: The medical records of 210 consecutive patients who underwent
laparoscopic cholecystectomy between January 2010 and December 2014 were
retrospectively evaluated. All laparoscopic cholecystectomies were initiated with
retrograde dissection (RD). In cases of difficulty in dissection of critical view
of safety , the operation strategy was first converted to FF and then to LPC when
FF was considered insufficient for safe cholecystectomy. RESULTS: Of the 210
cases, LC was initiated and completed with RD in 197 cases. FF was implemented in
13 cases due to difficulties in dissection. In the FF group, laparoscopic total
cholecystectomy was successfully accomplished in seven patients, and LPC was
performed in the remaining six cases. Three postoperative complications occurred
in the RD group and two in the LPC group. No major intraoperative complications
or perioperative mortality occurred in any patients. CONCLUSION: In elective,
noncomplicated cases, the safe posterior window (critical view of safety)
principle should be implemented. However, in complicated cases where anatomic
uncertainties are dominant, the performance of FF technique or LPC may decrease
conversion rates to open surgery and contribute to accomplishing the laparoscopic
intervention safely.
PMID- 29350372
TI - Endoscopic diagnosis and treatment of biliary obstruction due to acute
cholangitis and acute pancreatitis secondary to Fasciola hepatica infection.
AB - In the differential diagnosis of biliary obstruction with unknown etiology,
biliary fascioliasis should be considered in endemic and nonendemic regions.
After diagnostic evaluation, endoscopic retrograde cholangiopancreatography
(ERCP) was performed for etiological evaluation and/or treatment of biliary
obstruction in five patients with a mean age of 55.8 years. Endoscopic
sphincterotomy and cholangiogram revealed linear filling defects in the biliary
system. Fasciola hepatica parasites were extracted using balloon and basket
catheters in two and three patients, respectively. No morbidity or mortality was
observed. F. hepatica infection should be considered as a differential diagnosis
of biliary obstruction with unknown etiology in endemic and non-endemic regions.
ERCP can be the standard diagnostic and/or therapeutic procedure in cases of
biliary obstruction due to fascioliasis. Due to slippery and gel-like
characteristics of the parasite, use of a basket catheter in semi-opened position
may be required in case of unsuccessful extraction using a balloon catheter.
PMID- 29350373
TI - Pediatric dural venous sinus thrombosis following closed head injury: an easily
overlooked diagnosis with devastating consequences.
AB - Dural venous sinus thrombosis (DVST) is an uncommon finding after traumatic brain
injury. The diagnosis can often be initially missed, particularly if not
associated with an overlying fracture. Pediatric DVST following closed head
injury and without an overlying fracture is very rare, with only 20 cases
reported in the literature to date. Here we present the case of a 19-month-old
boy who presented with a history of trivial fall and an episode of fever. On
presentation, the pediatric Glasgow Coma Scale (pGCS) score was E3V4M6, and
initial brain computed tomography (CT) was normal. He was initially
conservatively managed. However, subsequent CT, taken following an episode of
seizure, revealed right tentorial subarachnoid hemorrhage and falx hematoma.
Conservative management was continued till he started developing recurrent
seizures with a decrease in pGCS scores. Repeat CT revealed sinus thrombosis that
involved the posterior aspect of the superior sagittal sinus with a massive brain
edema. The coagulation profile was normal, and no fracture overlying the sinus
was observed. Although he underwent emergency bifrontal decompressive craniotomy,
he did not recover. This study emphasizes on the importance of not missing the
diagnosis of sinus thrombosis and the devastating consequences that can occur if
it is overlooked.
PMID- 29350374
TI - Extension of a coronary intramural hematoma after blunt chest trauma.
AB - Coronary artery dissection and intramural hematoma after blunt chest trauma are
rare, but life-threatening, complications. Coronary intramural hematoma extension
is even rarer. A 31-year-old man was transferred to our hospital for worsening
left chest pain during while he was admitted at a nearby hospital due to blunt
chest trauma. Bedside echocardiography showed akinesis of the left ventricular
apex and anterior wall as well as hypokinesis of the mid-to-basal anteroseptal
wall and mid-to-basal lateral and posterior walls of the left ventricle. Computed
tomography coronary angiography revealed intramural hematoma in the left main
(LM) coronary and proximal left anterior descending (LAD) arteries. Percutaneous
coronary intervention, with bare metal stent implantation from the LM coronary
artery to the proximal LAD artery, was performed to treat the occlusion caused by
the hematoma. After stenting, the hematoma that compressed the LM coronary artery
shifted the left circumflex (LCX) artery, and the intramural hematoma developed
and extended to the LCX artery. To resolve this occlusion, a drug-eluting stent
was successfully implanted in the LCX artery. The patient was discharged without
complications. At 2-month follow-up, he remained asymptomatic, with no recurrence
of cardiovascular symptoms. Delayed chest pain after trauma should be suspected
during coronary dissection, and on treatment, care must be taken to extend the
hematoma.
PMID- 29350375
TI - Neurological recovery after traumatic Cauda Equina syndrome due to glass
fragments: An unusual case.
AB - Penetrating spinal injuries with foreign bodies are exceedingly rare. To date,
pathological problems due to glass fragments in the spinal canal have rarely been
reported. In this report, the case presenting with a back laceration, leg pain,
and leg weakness was found to have glass frag-ments in the spinal canal at the L2
L3 level by lumbar computed tomography and magnetic resonance imaging. After L2
total laminectomy and retrieval of the glass fragments, the dura was re-paired.
The patient was discharged from the hospital after complete neurological
recovery. In cases of spinal canal injuries due to foreign bodies, early
operative decompression of the neural elements is the treatment of choice.
Patients with Cauda Equina syndrome due to glass fragments have a good prognosis
for functional recovery.
PMID- 29350376
TI - An unexpected long-term complication of genital burn in a child: Secondary
cryptorchidism.
AB - Genital and perineal burns are rare and challenging injuries with serious long
term complications. Involvement of the testes is a sign of severity. There is
limited knowledge in the literature about the management of complications and
testes involvement in genital and perineal burns. In this report, we present the
case of an 8-year-old boy with secondary cryptorchidism due to burn contracture
who was treated by increasing the scrotal volume by Z-plasties, skin graft, and
orchidopexy.
PMID- 29350377
TI - Melatonin exhibits supportive effects on oxidants and anastomotic healing during
intestinal ischemia/reperfusion injury.
AB - BACKGROUND: The aim of this study was to investigate the effects of melatonin on
intestinal anastomosis after intestinal ischemia/ reperfusion injury (IRI).
METHODS: Thirty Wistar albino rats of both sexes were divided into 3 groups:
sham, control, and treatment. IRI was performed by clamping the superior
mesenteric artery (SMA) for 30 minutes, followed by reperfusion. The sham rats
received only manipulation of the SMA. Melatonin (10 mg/kg) was administered to
the treatment group, and the control group was given a vehicle injection. Both
the treatment group and the control group further underwent ileal resection of a
1-cm segment and anastomosis. On the postoperative seventh day, the anastomotic
burst pressure, hydroxyproline level, histological indices of wound healing, and
oxidative parameters of catalase (CAT), superoxide dismutase (SOD), total
glutathione (T-GSH), and glutathione peroxidase (GSH-Px) levels were measured. A
one-way analysis of variance and chi-square test were used for the categorical
data. RESULTS: Melatonin treatment led to a significantly higher burst pressure
(p=0.027 and p<0.001, respectively). The 2 antioxidant enzymes, CAT and SOD, were
at the highest level in the sham and melatonin groups and the lowest level in the
control group (p=0.001 and p=0.002, respectively). Melatonin treatment resulted
in a significantly higher level of both enzymes compared with the control group
(p=0.026 and 0.003, respectively). The GSHpx and total GSH levels were slightly
elevated in the treated rats, but the difference was not statistically
significant (p=0.205 and 0.216, respectively). Fibroblast infiltration, capillary
formation, and epithelialization were significantly better in the melatonin
treated animals. The granulocyte and mononuclear infiltration scores were similar
between all groups. CONCLUSION: It was concluded that melatonin had marked
effects on intestinal anastomotic healing during intestinal IRI.
PMID- 29350378
TI - EQ-5D studies in cardiovascular diseases in eight Central and Eastern European
countries: a systematic review of the literature.
AB - BACKGROUND: The measurement of health-related quality of life (HRQoL) by
validated generic instruments, such as EQ-5D, has become an increasingly
important tool for the assessment of health care in a wide range of diagnoses.
AIM: We aimed to systematically review EQ-5D literature on cardiovascular
diseases in eight Central and Eastern European (CEE) countries. METHODS: A
structured literature search was conducted in MEDLINE, EMBASE, Web of Science,
CINAHL, PsycINFO, Cochrane Library, and the EuroQol website up to November 2016.
Original cardiovascular-related studies that reported EQ-5D results were
included. RESULTS: Of the 36 papers, 17 reported EQ-5D index scores. Most studies
were performed in Poland (n = 24, 67%). The most common diagnosis regarding the
number of publications and population size was ischaemic heart disease (n = 13, N
= 6394), followed by atrial fibrillation (n = 4, N = 1052). The average EQ-5D
index scores ranged from 0.61 to 0.88 and from 0.66 to 0.95 for patients before
and after cardiac procedure/surgery, respectively (including angioplasty,
coronary artery bypass grafting, ablation, surgical correction of septal defects,
transcatheter aortic valve implantation [TAVI]). In all studies baseline scores
were lower than the repeated assessments after the procedure, with the most
substantial improvement of 0.24 in high-risk elderly patients after TAVI. Studies
which did not assess invasive treatment reported mean EQ-5D index scores ranging
from 0.18 to 0.80. CONCLUSIONS: The number of cardiovascular-related studies
reporting HRQoL using EQ-5D has consistently increased in CEE countries over the
past decade and is outstanding compared with other clinical fields. The EQ-5D
index and EQ VAS scores varied based on the disease severity, patient
characteristics, and treatment protocol.
PMID- 29350379
TI - Metabolic syndrome in HIV infected adults in Poland.
AB - BACKGROUND: Metabolic syndrome (MS) is usually diagnosed based on the presence of
abdominal obesity, elevated blood pres-sure (BP), elevated fasting plasma
glucose, high serum triglycerides (TG), and low high-density lipoprotein (HDL)
cholesterol levels. Whether HIV is associated with a higher prevalence of MS than
in the general population remains unclear. AIM: The aim of the study was to
determine the incidence of MS in the population of HIV-infected adults and its
association with clinical, virological, and biochemical features. METHODS: Two
hundred and seventy HIV-infected Caucasian adult patients were enrolled in the
study and evaluated based on clinical records in the years 2013-2015. RESULTS:
Metabolic syndrome was diagnosed in 60 of 270 (22%) patients, 47 (24%) males and
13 (17%) females, mostly (72%) aged above 40 years. The percentage of patients
with diagnosed MS in specific age groups in comparison to the general Polish
population for females aged < 40 years was 7% vs. 4%, and males in the same age -
18% vs. 9%, for females aged 40-59 years - 47% vs. 24.4%, and males - 33% vs.
28.3%. Particular components of MS in the MS population were found as follows:
body mass index > 30 kg/m2 in 29%, waist circumference exceeding 94 cm in men and
80 cm in woman - 87.5%, TG >= 150 mg/dL - 82%, HDL cholesterol < 40/50 mg/dL
(males/females) - 42%, systolic/diastolic BP >= 130 mmHg/>= 85 mmHg - 83%, and
fasting glucose > 100 mg/dL - 42%. In stepwise multivariate logistic regression
analysis, age (odds ratio [OR] 1.052, 95% con-fidence interval [CI] 1.018-1.088,
p = 0.003) and nadir CD4 < 350 cells/mm3 (OR 3.576, 95% CI 1.035-12.355, p =
0.04) were associated with MS. Patients with MS compared with those without this
disorder had low, intermediate, high, and very high cardiovascular risk in 10%
vs. 23%, 73% vs. 70%, 7% vs. 5%, and 10% vs. 2%, respectively (p = 0.006).
CONCLUSIONS: Prevalence of MS in the HIV-infected population is higher than in
the general Polish population. Age and low nadir CD4 were found to be associated
with MS.
PMID- 29350380
TI - Patients treated with bivalirudin are still at higher risk of stent thrombosis: a
comprehensive meta-analysis of randomised clinical trials of bivalirudin and
heparin for percutaneous coronary interventions.
AB - BACKGROUND: Although the current practice guidelines recommend using both heparin
and bivalirudin for percutaneous coronary interventions (PCI), the research data
are ambiguous. AIM: The aim of the study was to compare the impact of bivalirudin
and heparin on major clinical endpoints in PCI patients with particular emphasis
on periprocedural stent thrombosis. METHODS: A total of 18 randomised clinical
trials involving 41,752 subjects were included. The endpoints comprised: net
adverse clinical event (NACE: death, myocardial infarction [MI], unscheduled
revascularisation, major bleeding), major adverse cardiovascular event (MACE:
death, MI, or stroke), and acute/subacute stent thrombosis (ST). A subanalysis
for planned and provisional glycoprotein IIb/IIIa inhibitor (GPI) use with
heparin was performed. Results were presented as risk ratios (RR) and 95%
confidence intervals (CI). RESULTS: Bivalirudin significantly reduced NACE risk
(RR 0.85, 95% CI 0.76-0.96) and increased the incidence of MI (RR 1.09, 95% CI
1.01-1.18), ST (RR 1.50, 95% CI 1.13-1.99), and MACEs (RR 1.06, 95% CI 0.99
1.13). Comparing to heparin with provisional or planned GPI use, there was higher
risk of acute ST with bivalirudin (RR 2.14, 95% CI 1.01-4.56 and RR 5.53, 95% CI
2.32-13.18, respectively). Comparing to heparin and provisional GPIs, bivalirudin
failed to reduce NACEs and major bleeding. However, it decreased rates of NACEs
(RR 0.81, 95% CI 0.69-0.96) and major bleeding (RR 0.64, 95% CI 0.48-0.85)
compared with heparin and planned GPI use. CONCLUSIONS: The advantages of
bivalirudin are undoubtedly related to GPI use in the heparin arms. Bivalirudin
based regimens are more beneficial when compared with heparin and planned GPI use
in terms of NACE and major bleedings; this was not observed when compared to
heparin and provisional GPI use. Regardless of adjunctive GPI use, stent
thrombosis episodes were significantly more common in bivalirudin-treated
subjects. Therefore, the safety and economic issues may urge revision of this
aspect of current clinical practice and guidelines.
PMID- 29350381
TI - Macrophage migration inhibitory factor knockout attenuates endotoxin-induced
cardiac dysfunction in mice.
AB - BACKGROUND: Accumulated evidence suggests that macrophage migration inhibitory
factor (MIF) plays a key role not only in acute and chronic inflammatory diseases
but also in cardiovascular disease. The cardiac dysfunction is related to
lipopolysac-charide (LPS) in sepsis. AIM: This study was designed to examine
whether MIF mediates LPS-induced cardiac dysfunction and address the mechanisms.
METHODS: Echocardiography, immunohistochemical analysis, cell shortening/re
lengthening, and intracellular Ca2+ fluores-cence evaluation were performed in
whole hearts and isolated cardiomyocytes from C57 and MIF knockout mice treated
with or without LPS. Reactive oxygen species and protein carbonyl formation were
measured. Activation of mitogen-activated protein kinases and endoplasmic
reticulum stress markers were evaluated using Western blot analysis. Human
umbilical vein endothelial cells (HUVECs) were transfected with lentiviruses
carrying short hairpin RNA (shRNA) to inhibit MIF. RESULTS: Echocardiography
revealed that cardiac function was impaired and macrophage infiltration was
increased in LPS-treated C57 mice. Peak shortening and maximal velocity of
shortening/re-lengthening were significantly reduced and the duration of re
lengthening was prolonged in LPS-treated C57 mice. Reactive oxygen species and
protein carbonyl levels were increased in LPS-treated C57 mice. These
dysfunctional changes were attenuated in MIF knockout mice that were challenged
with LPS. Western blot analysis revealed that activated p-JNK, p-ERK, and
endoplasmic reticulum stress protein marker expression was decreased in LPS
treated MIF knockout mice. p-ERK and p-JNK levels were knocked down in MIF shRNA
transfected HUVECs. CONCLUSIONS: The data collectively suggest that MIF mediates
LPS-induced cardiac dysfunction in murine cardiomyocytes, which was attenuated by
MIF knockout, and the therapeutic option with regard to MIF may aid the
management of cardiac dysfunction in sepsis.
PMID- 29350382
TI - Risk factors for adverse outcomes of patients with acute coronary syndrome:
single-centre experience with long-term follow-up of treated patients.
AB - BACKGROUND: For patients experiencing an acute coronary syndrome (ACS), a crucial
time to assess their prognosis and to plan management is at discharge from
hospital. AIM: The aim of the study was to identify risk factors of mortality
during post-discharge period following a hospitalisation for ACS. METHODS: We
studied 672 consecutive ACS patients hospitalised and discharged alive between
2002 and 2004. The analysis was done with respect to the type of ACS, i.e.
unstable angina/non-ST-segment elevation myocardial infraction (UA/NSTEMI; n =
255) vs. ST-segment elevation myocardial infarction (STEMI; n = 417). All
patients underwent coronary angiography and, if indicated, primary angioplasty
(STEMI: 417 patients; UA/NSTEMI: 157 patients). The Cox proportional hazards
regression model was used to evaluate the independent effect of the risk factors
on the occurrence of primary endpoint, i.e. all-cause mortality during six-year
follow-up. Survival status and date of death were obtained from the National
Registry of Population (PESEL database). RESULTS: A total of 123 patients (18.3%)
died within the post-discharge period. The multivariate analysis identified 11
highly significant independent predictors of mortality (in order of predictive
strength): diabetes mellitus (all types), higher creatinine level, older age, and
more frequent occurrence of: supraventricular arrhythmias during hospitalisation,
peripheral artery disease, recurrent angina pectoris with documented ischaemia on
electrocardiogram, male sex, prior myocardial infarction, treatment with intra
aortic balloon pump counterpulsation, heart failure, and higher peak levels of
creatine kinase-MB. CONCLUSIONS: The risk factors obtained from the medical
history and during the hospitalisation improve the risk stratification during the
post-discharge period after hospitalisation for ACS.
PMID- 29350383
TI - Which position should we take during newborn resuscitation? A prospective,
randomised, multicentre simulation trial.
AB - BACKGROUND: Early bystander cardiopulmonary resuscitation (CPR) for cardiac
arrest is crucial in the chain of survival. Cardiac arrest in infants is rare,
but CPR is also performed in severe bradycardia. European Resuscitation Council
and American Heart Association guidelines recommend continuing CPR until the
heart muscle is sufficiently oxygenated and regains sufficient contractility and
function. The most common and recommended CPR techniques that can be applied in
newborns are the two-finger technique and two-thumb technique. AIM: We sought to
assess the quality of CPR performed in newborns with the two-finger technique
depending on the posi-tion of the rescuer during resuscitation. METHODS: This was
a prospective, randomised, crossover, simulated study. It involved 93 nurses who
were required to perform a two-minute CPR using the two-finger technique in three
scenarios: (A) with the newborn lying on the floor; (B) on a table; and (C) with
the newborn on the rescuer's forearm. The Newborn Tory(r) S2210 manikin was used
to simulate a neonatal patient in cardiac arrest. The following parameters were
measured: chest compression (CC) depth, CC rate, no-flow time, percentage of full
release, ventilation rate, and ventilation volume, as well as the number of
effective compressions and effective ventilations. RESULTS: Statistical analysis
showed significant differences in CC rates between scenarios A and B (p < 0.001)
and between scenarios B and C (p = 0.002). Significant differences were also
observed between the median CC depth. The median per-centage of no-flow-fraction
was the highest for scenario A (55%), followed by scenario B (48%), and scenario
C (46%). There were significant differences between the values of no-flow
fraction between scenarios A and B (p < 0.001), and between scenarios A and C (p
< 0.001). The percentage of chest full releases for scenarios A, B, and C
amounted to 94%, 1%, and 92%, respectively. Significant differences in the number
of effective CCs between scenarios A and B (p < 0.001) as well as B and C (p <
0.001) were revealed. The median ventilation rate was highest for scenario B (13
* min-1), and lowest for scenario A (9 * min-1). The highest tidal volume was
obtained in scenario A (27 mL), and the lowest in scenario C (26 mL). The most
effective CPR was performed when resuscitation was carried out on the rescuer's
forearm. CONCLUSIONS: The quality of CCs in newborns depends on the location of
the patient and the rescuer. The optimal form of resuscitation of newborns is
resuscitation on the rescuer's forearm.
PMID- 29350384
TI - The importance of psychosocial factors in management of pulmonary arterial
hypertension patients.
PMID- 29350385
TI - Impact of previous cardiac surgery with sternotomy on clinical outcomes and
quality of life after transcatheter aortic valve implantation for severe aortic
stenosis.
AB - BACKGROUND: Transcatheter aortic valve implantation (TAVI) has evolved as an
effective treatment in patients with symptomatic severe aortic stenosis (AS) and
increased operative risk. Data on the influence of previous sternotomy on the
risk of TAVI are limited. AIM: We sought to investigate the effect of previous
cardiac surgery with sternotomy on clinical outcomes and quality of life (QoL)
after TAVI. METHODS: The study included 148 consecutive patients with symptomatic
severe AS, who underwent TAVI. Baseline charac-teristics, procedural and long
term clinical outcomes, and QoL assessment with the EQ-5D-3L questionnaire were
compared between patients with and without previous sternotomy. RESULTS: Patients
with previous sternotomy (23.0% of the population) were younger and more often
male, had higher rate of previous myocardial infarction (MI; 26 [22.8%] vs. 22
[64.7%], p = 0.001), and lower median left ventricular ejection frac-tion (60.0%
[50.0-65.0] vs. 50.0% [42.0-60.0], p = 0.004). Periprocedural risk measured with
the Logistic Euroscore and the Society of Thoracic Surgeons scale was comparable
in both groups. There were no differences in 30-day and 12-month all-cause
mortality between the groups with and without sternotomy (10 [8.8%] vs. 2 [5.9%],
p = 0.7; odds ratio [OR] adjusted for age/sex/previous MI, 0.56, 95% confidence
interval [CI] 0.10-3.29; for 12-month mortality adjusted OR 0.19, 95% CI 0.04
0.99). At the longest available follow-up, mortality was higher in patients
without sternotomy (30 [26.3%] vs. 3 [8.8%], p = 0.03; adjusted OR 0.10, 95% CI
0.02-0.42). Similar rates of other complications after TAVI were noted. No
differences in the EQ-5D-3L questionnaire at baseline and 12-month follow-up were
confirmed. CONCLUSIONS: TAVI seems to be a safe and effective technique for the
treatment of severe AS in patients with previous cardiac surgery.
PMID- 29350386
TI - Comparison of clinical characteristics of real-life atrial fibrillation patients
treated with vitamin K antagonists, dabigatran, and rivaroxaban: results from the
CRAFT study.
AB - BACKGROUND: The first-line drugs for the treatment of non-valvular atrial
fibrillation (AF) are non-vitamin K antagonist oral anticoagulants (NOACs), which
are preferred over vitamin K antagonists (VKAs). There is some evidence that
there are dis-crepancies between everyday clinical practice and the guidelines.
AIM: The study aimed to compare the characteristics of patients on VKAs,
dabigatran, and rivaroxaban in everyday practice (i.e. baseline characteristics,
drug doses, risk factors for bleeding and thromboembolic events). Additionally,
we assessed the frequency of prescription of different oral anticoagulants (OACs)
in recent years. METHODS: This study consisted of data from the multicentre CRAFT
(MultiCentre expeRience in AFib patients Treated with OAC) study (NCT02987062).
This was a retrospective analysis of hospital records of AF patients
(hospitalised in the years 2011-2016) treated with VKAs (acenocoumarol, warfarin)
and NOACs (dabigatran, rivaroxaban). A total of 3528 patients with non-valvular
AF were enrolled in the CRAFT study. RESULTS: The total cohort consisted of 1973
patients on VKA, 504 patients on dabigatran, and 1051 patients on rivaroxaban.
Patients on rivaroxaban were older (70.5 +/- 13.1 years) and more often female
(47.9%), compared with those on VKAs (67.0 +/- 12.8 years, p < 0.001; 35.5%, p <
0.001) and on dabigatran (66.0 +/- 13.9 years, p < 0.001; 38.9%, p = 0.001).
Among NOACs, patients with persistent and permanent AF were more likely to
receive rivaroxaban (54.7% and 73.4%, re-spectively) than dabigatran (45.3%, p <
0.001 and 26.6%, p = 0.002, respectively). Patients on rivaroxaban had higher
risk of thromboembolic events (CHA2DS2VASc 3.9 +/- 2.0, CHADS2 2.2 +/- 1.4) than
those on VKAs (3.3 +/- 2.0, 1.9 +/- 1.3) and on dabigatran (3.1 +/- 2.0, 1.8 +/-
1.3). Patients on rivaroxaban had also a higher rate of prior major bleeding
(11.2%) than those on VKAs (6.7%, p < 0.001) and on dabigatran (7.3%, p = 0.02).
Patients on lower doses of dabigatran and rivaroxaban had a significantly higher
risk of thromboembolic and bleeding events. Use of VKAs in the year 2011 was
reported in over 96% of patients on OACs, but this proportion decreased to 34.6%
in 2016. In the last analysed year (2016) AF patients were treated mainly with
NOACs - dabigatran (24.2%) and rivaroxaban (41.3%). CONCLUSIONS: The prescription
of VKAs declined significantly after the introduction of NOACs. Patients treated
with different OACs demonstrated a distinct baseline clinical profile. The
highest risk of thromboembolic events and incidence of major bleedings was
observed in patients on rivaroxaban, in comparison to patients on VKAs and
dabigatran. Among NOACs, patients treated with lower doses of dabigatran and
rivaroxaban were older and had a significantly higher risk of thromboembolic and
bleeding events.
PMID- 29350387
TI - Clinical anatomy of human heart atria and interatrial septum - anatomical basis
for interventional cardiologists and electrocardiologists. Part 1: right atrium
and interatrial septum.
PMID- 29350388
TI - Chronic statin treatment is a predictor of pre-interventional infarct-related
artery patency in patients with ST elevation myocardial infarction treated with
percutaneous coronary intervention.
AB - BACKGROUND: Beyond lipid-lowering effects, early statin treatment has beneficial
effects on prognosis after acute coronary syndrome. Infarct-related artery (IRA)
patency before percutaneous coronary intervention (PCI) is known to be a strong
pre-dictor of improved clinical outcome. AIM: We aimed to investigate the effects
of chronic statin treatment before admission on IRA patency after myocardial
infarction. METHODS: In this study, 938 ST elevation myocardial infarction
(STEMI) patients admitted to the hospital within the first 12 h of symptom onset
were prospectively enrolled (male, n = 682; female, n = 256; mean age 58.6 +/-
12.4 years). All patients underwent emergent primary PCI. Patients were divided
into two groups based upon angiographic IRA patency. Impaired IRA patency was
defined as Thrombolysis In Myocardial Infarction (TIMI) grade 0 and 1 flow (non
patent IRA group). Angiographic IRA patency was defined as TIMI 2 and 3 flow
(patent IRA group). RESULTS: Previous statin usage was more frequent in the
patent IRA group (n = 138; 71.9%), than in the non-patent IRA group (n = 110;
14.7%; p < 0.001). Pre-PCI IRA patency was independently associated with body
mass index (odds ra-tio [OR] = 1.087, 95% confidence interval [CI] 1.005-1.176, p
< 0.001), previous chronic statin use (OR 0.065, 95% CI 0.043-0.098, p = 0.039),
ejection fraction (OR 1.041, 95% CI 1.018-1.064, p < 0.001), and SYNTAX score (OR
0.927, 95% CI 0.899-0.957, p < 0.001) in multivariate logistic regression
analysis. CONCLUSIONS: Chronic pre-treatment with statins is a significant
predictor of the IRA patency in patients with STEMI.
PMID- 29350389
TI - Three-dimensional visualisation of coronary sinus ostium from the inside right
atrium perspective.
AB - BACKGROUND: There is no in vivo method of coronary sinus visualisation from the
right atrium perspective. AIM: The objective of the study was to create a cardiac
computed tomography (CT) angiography-based method of visualising the coronary
sinus ostium and the Thebesian valve from the inside right atrium perspective.
METHODS: In 78 consecutive patients, a cardiac CT angiography (Aquilion 64,
Toshiba) with retrospective gating (slice 0.5 mm) was performed. Raw data were
reconstructed on Vitrea 2 workstations (Vital Images). In order to create the
three-dimensional (3D) coronary sinus visualisation from the "inside view"
perspective, patented "Fly Through" algorithms were used, and the anatomical
positions on the multiplanar reconstruction images were marked. A dedicated,
Likert-based five-point scale was developed and used to evaluate the quality of
the visualisations. RESULTS: The average quality of the visualisations of the
coronary sinus ostium in two-dimensional multiplanar reconstruction images was
good (4.17 +/- 0.85 points) and was clinically interpretable in all cases. The
image quality of the "inside view" 3D images was 3.61 +/- 1.12 points. In 57.7%
of cases we obtained high scores (4 and 5 points). The main diameter was 10.72 +/
2.48 mm, and the entrance angle of the coronary sinus into the right atrium was
103.76 +/- 10.71 degrees . CONCLUSIONS: Cardiac CT angiography is a useful method
that permits the coronary sinus ostium and Thebesian valve to be visualised in
vivo from the inside of the right atrium in a comparable manner.
PMID- 29350390
TI - Dual antiplatelet therapy is safe and efficient after left atrial appendage
closure.
AB - BACKGROUND: Despite results of the PROTECT AF trial, many patients undergoing
left atrial appendage closure (LAAC) have unconditional contraindications to
warfarin. AIM: We sought to investigate whether double antiplatelet therapy
(DAPT) is safe in patients after LAAC. METHODS: Forty-four consecutive patients
(22 males, mean age 74 +/- 7.8 years) with non-valvular atrial fibrillation
(NVAF) underwent LAAC procedure using a Watchman device followed by DAPT (75 mg/d
aspirin and 75 mg/d clopidogrel). After the procedure and during 98 days' follow
up including transoesophageal echocardiography, peri-procedural complications and
clinical outcomes were investigated. RESULTS: Mean CHA2DS2-VASc score was 4.9 +/-
1.5 and mean HAS-BLED score was 3.6 +/- 0.8. The main LAAC indication was
contraindication to anticoagulation reflected by HAS-BLED score >= 3 observed in
95.5% cases (among them history of bleeding in 38 patients, 90.5%). 36.4% of
patients have history of stroke or transient ischaemic attack. The procedure was
successful in 97.7%. Peri-procedural complications were tamponade (2.3%) and one
death (2.3%) unrelated to the procedure with no bleeding or vascular
complications. During follow-up neither stroke nor bleeding were observed,
whereas two device related thrombi and two unrelated deaths occurred.
CONCLUSIONS: LAAC followed by DAPT seems to be a safe and efficient alternative
for stroke prevention in patients with NVAF who have contraindications to
anticoagulation therapy. This strategy may provide a significant reduction of
events such as stroke and bleeding versus the score-predicted rate.
PMID- 29350391
TI - Polish single-centre follow-up of subcutaneous implantable cardioverter
defibrillator (S-ICD) systems implanted for the prevention of sudden cardiac
death.
AB - BACKGROUND AND AIM: Subcutaneous implantable cardioverter-defibrillator (S-ICD)
is an effective and modern tool used to protect patients at risk of sudden
cardiac death (SCD) from potentially life-threatening ventricular arrhythmias.
The first S-ICD systems were implanted in Poland in 2014, but since that time the
national experience with that therapy has been limited. Our analysis summarises
the single-centre experience at the Department of Cardiology and Electrotherapy
of the Medical University of Gdansk with the use of S-ICD from the year 2014 to
2017. METHODS AND RESULTS: The S-ICD therapy was used in 12 patients (five male,
seven female, mean age 57.2 +/- 12.5 years), in eight of them for the secondary
prevention of SCD. No surgical complications of implantation procedures were
observed during the perioperative hospitalisation nor during follow-up. During
the mean follow-up of 14 +/- 13 months we observed the appropriate function of
the systems and a ventricular fibrillation episode successfully terminated by the
device in one patient, two cases of S-ICD sensing problems (one of which led to
inadequate intervention of the device), and an episode of atrial fibrillation
also leading to inadequate intervention in another patient. CONCLUSIONS: S-ICD,
being an effective and safe method used to treat patients at risk of SCD, may be
safely and successfully introduced into clinical practice in centres new to that
field. The number of complications during the initial experience and introduction
of that method may be kept low if the operating team is experienced enough in
cardiac electrotherapy.
PMID- 29350392
TI - Diagnostic and prognostic micro-RNAs in ischaemic stroke due to carotid artery
stenosis and in acute coronary syndrome: a four-year prospective study.
AB - BACKGROUND: Circulating microRNAs (miRs) levels are potentially important
diagnostic and prognostic biomarkers in acute coronary syndrome (ACS) or cerebral
ischaemic events (CIE) resulting from internal carotid artery stenosis (ICAS).
AIM: This four-year prospective study aimed to compare the levels of circulating
miRs in ACS vs. CIE patients, and investigate miRs potentially associated with
risk of recurrent cardiovascular events. METHODS: The circulating miRs levels
(miR-1-3p, miR-16-5p, miR-34a-5p, mir-122-5p, miR-124-3p, miR-133a-3p, miR-133b,
miR-134-5p, miR-208b-3p, miR-375, and miR-499-5p) were compared in 43 (34 men,
57.6 +/- 10.1 years) patients with ACS, and in 71 (47 men, 69.5 +/- 9.6 years)
with CIE due to ICAS. A four-year prospective evaluation of miRs associated with
risk of cardiovascular death (CVD), myocardial infarction (MI), CIE, or all
(CVD/MI/CIE) was performed. RESULTS: In ACS vs. CIE patients, the levels of miR
124-3p (p < 0.001), miR-134-5p (p = 0.012), miR-208b-3p (p < 0.001), miR-34a-5p
(p < 0.001), and miR-499-5p (p < 0.001) were higher, while levels of miR-16-5p (p
< 0.001) and miR-122-5p (p < 0.001) were lower. Levels of miR-1-3p (p = 0.195),
miR-133a-3p (p = 0.333), miR-133b (p = 0.056), and miR-375 (p = 0.055) were non
statistically different. During follow-up (median 57 months, Q1-Q3: 54-60),
CVD/MI/CIE occurred in 23 subjects, including eight CVDs, five non-fatal CIEs,
and 10 non-fatal MIs. The multivariate Cox proportional hazard analysis (relative
risk [RR]; 95% confidence interval [CI]) revealed that miR-208b-3p (1.225; 1.092
1.375), miR-34a-5p (0.963; 0.935-0.992), and miR-499-5p (0.077; 0.025-0.239) were
independently associated with risk of CVD/MI/CIE, as well as risk of each event.
Furthermore, miR-133b (1.009; 1.003-1.015) was associated with risk of CVD.
CONCLUSIONS: This study shows that although most investigated miRs levels differ
significantly between patients with ACS and CIE, similar levels of circulating
miR-1-3p, miR-133a-3p, miR-133b, and miR-375 were observed; furthermore, we
identified several common miRs as possible risk factors for recurrent
cardiovascular events.
PMID- 29350393
TI - Is it possible to improve compliance in hypertension and reduce therapeutic
inertia of physicians by mandatory periodic examinations of workers?
AB - BACKGROUND: Due to high prevalence, insufficient recognition, and ineffective
treatment, hypertension (HT) still remains a major medical and socio-economic
problem. There is a real necessity to develop effective prophylaxis for
cardiovascular disorders (CVD), based on strategies that support compliance
during long-term therapy. The Polish scheme of occupational health services with
mandatory periodical employee check-ups creates a unique opportunity for
effective HT prophylaxis. As a result, visiting a doctor is required not only due
to health ailments but also by law, which is especially important for those
feeling well. It enables an improvement in tertiary prevention, including actions
taken not only by the doctors of the occupa-tional health services, but also by
the physicians in charge of treating the patients. AIM: Evaluation of the
usefulness of mandatory health check-ups of employees concerning frequency of
diagnosis and im-provement of treatment outcomes of HT. METHODS: The study group
comprised 1010 Polish workers referred by their employers for mandatory medical
examinations. All of the study participants filled in a questionnaire focused on
self-assessment of their health, current blood pressure (BP) mea-surements, and
in cases where HT had been previously detected - compliance with medical
recommendations. Then in the doctor's office BP measurements were taken twice.
Workers who fulfilled a criterion indicating a need for intervention were
educated on optimal diet, physical activity, and risk factors for CVD. They also
received medical instructions for three-step action. The first recommendation:
measure BP three times a day for one week and record the results. The second:
visit a gen-eral practitioner (GP) for a professional assessment of those
results. The third: re-visit the occupational health physician within three
months. The criterion for intervention was prior HT and a mean of two BP
measurements >= 180/110 mmHg - in each case, or >= 140/90 mmHg - in the case of
occupational exposure to risk factors for CVD. RESULTS: The mean age of the study
participants was 41.7 years (similar in both genders). A previous diagnosis of HT
was declared by 20.1% of patients. 11% of patients involved in the intervention
did not comply with medical advice. The current HT therapy of all of the subjects
with HT (100% of those with abnormal BP, who visited their GP) was modified.
CONCLUSIONS: Prophylactic medical check-ups of workers gives improved compliance
and medical surveillance of HT in patients with an uncontrolled clinical course
of this disease. Obligations and periodic examinations encourage both patients
and physicians to improve compliance and reduce the risk of therapeutic inertia.
PMID- 29350394
TI - Genetic variants in a Polish population of patients with pulmonary arterial
hypertension: sequencing of BMPR2, ALK1, and ENG genes.
AB - BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with a very
serious prognosis. It seems that mutations in genes related to transforming
growth factor-b signalling pathway are often related to the development of the
disease. No study covers this problem in a Polish population. AIM: To screen for
genetic mutations in a Polish cohort of patients with pulmonary hypertension,
especially with idiopathic PAH, treated in a single hospital in Poland. METHODS:
DNA sequencing method was used. Samples from 50 patients with pulmonary
hypertension were screened for mutations in type 2 bone morphogenetic protein
receptor of the transforming growth factor-b superfamily gene (BMPR2). Samples
from 20 patients with idiopathic PAH (11 men, mean age 55 years) were also
screened for mutations in activin A receptor-like type 1 gene (ALK1) and endoglin
gene (ENG). RESULTS: No genetic variations were found for the BMPR2 gene. In all
20 samples from idiopathic pulmonary hypertension patients we found
heterozygosity of single nucleotide polymorphism (SNP) rs 372023206 in ALK1 gene.
Three samples from these patients showed variations of ENG gene: we found one
sample with heterozygosity of SNP rs 200525684, one with heterozygosity of SNP rs
3739817, and one with both. CONCLUSIONS: We detected benign polymorphisms or
genetic variants of unknown importance. It is possible that the Polish population
of PAH patients differs from the previously described populations of other
countries in terms of the frequency and importance of mutations in BMPR2, ALK1
and ENG genes.
PMID- 29350395
TI - Early results of aortic arch reconstruction and bilateral pulmonary artery
banding: modification of the Norwood operation for treatment of hypoplastic left
heart syndrome.
AB - BACKGROUND: In the period from 2003 to the end of 2015, 96 Norwood I procedures
were performed in the Paediatric Heart Surgery Department in Katowice, Poland, in
children with hypoplastic left heart syndrome (HLHS). AIM: This paper presents a
retrospective analysis of early surgical results. METHODS: The patients consisted
of two groups: group I included 59 children operated on in the years 2003-2012,
in whom the stage I Norwood procedure with the Sano modification was performed
with the aortic arch reconstructed by use of a ho-mogenous pulmonary artery patch
or a bovine pericardial patch. Group II included 37 children after our
modification of the Norwood I procedure, in which the aortic arch was
reconstructed with an extracellular matrix patch and bilateral pulmonary artery
banding was done. RESULTS: Aortic cross-clamping time was significantly shorter
in group II (mean 52; range 38-62 min) than in group I (mean 57; range 39-72 min;
p < 0.009). Eighteen (30.5%) children in group I and six (16.2%) in group II
died. Although this dif-ference did not reach statistical significance (p =
0.12), it suggested that improved outcomes with the modified procedure are
possible. The cause of death in group I was significantly more frequently due to
massive postoperative bleeding (n = 6; 33.3%) than in group II (n = 1; 16.7%; p =
0.046). CONCLUSIONS: The introduction of this new surgical technique reduced
postoperative bleeding rates, shortened the operation time, and might improve the
mortality rate in the first-stage surgical treatment of children with HLHS.
PMID- 29350396
TI - Tobacco regulation as a paradigm for advancing regulatory science in dermatology.
PMID- 29350397
TI - The burden of non-melanoma skin cancers in Auckland, New Zealand.
AB - BACKGROUND/OBJECTIVES: As the New Zealand Cancer Registry does not require
mandatory reporting of non-melanoma skin cancers (NMSC), basal cell carcinomas
(BCC) and squamous cell carcinomas (SCC), the clinical burden of these diseases
is unknown. METHODS: A retrospective review of all patients with histopathology
performed allowed us to estimate invasive BCC and SCC in the Auckland region in
2008 (population 1.44 million). RESULTS: During this period, a total of 21 236
NMSC were diagnosed among 13 996 patients, consisting of 5611 SCC lesions (26%)
and 15 525 (74%) BCC. The Auckland incidence rates per 100 000 were 425 for SCC
and 1177 for BCC. The overall rate of NMSC per 100 000 was 1906.5 (standardised
to the census data of Australia 2001); 1385 for BCC and 522 for SCC. Using
published data on incidence trends and population growth, we estimate that 29 000
33 000 NMSC would have been excised in Auckland in 2016, and 78 000-87 000 in New
Zealand. CONCLUSION: Auckland has the highest reported incidence of invasive NMSC
in the world. We believe that high-risk cutaneous SCC and complex BCC should be
recorded. Our study provides information for clinicians and health economists on
the scale of the problem.
PMID- 29350398
TI - Use of Computational Functional Genomics in Drug Discovery and Repurposing for
Analgesic Indications.
AB - The novel research area of functional genomics investigates biochemical,
cellular, or physiological properties of gene products with the goal of
understanding the relationship between the genome and the phenotype. These
developments have made analgesic drug research a data-rich discipline mastered
only by making use of parallel developments in computer science, including the
establishment of knowledge bases, mining methods for big data, machine-learning,
and artificial intelligence, (Table ) which will be exemplarily introduced in the
following.
PMID- 29350399
TI - Biological functions of Elabela, a novel endogenous ligand of APJ receptor.
AB - The G protein-coupled receptor APJ and its cognate ligand, apelin, are widely
expressed throughout human body. They are implicated in different key
physiological processes such as angiogenesis, cardiovascular functions, fluid
homeostasis, and energy metabolism regulation. Recently, a new endogenous
peptidic ligand of APJ, named Elabela, has been identified and shown to play a
crucial role in embryonic development. In addition, increasing evidences show
that Elabela is also intimate associated with a large number of physiological
processes in adulthood. However, a comprehensive summary of Elabela has not been
reported to date. In this review, we provide an overview of the biological
functions of Elabela. Collectively, Elabela, a potential therapeutic peptide,
exerts diverse biological functions in both embryos and adult organisms, such as
dysontogenesis, self-renewing of human embryonic stem cells, endoderm
differentiation, heart morphogenesis, cardiac dyfunctions, blood pressure
control, angiogenesis, blood pressure control, regulation of food and water
intake, bone formation, and kidney diseases.
PMID- 29350400
TI - Feasibility of Enteral Protein Supplementation in Critically Ill Children.
AB - BACKGROUND: We describe the protein type and concentration in standard enteral
nutrition (EN) formulas and the effect of protein supplementation on the
osmolality of standard formulas. We also aimed to examine factors associated with
optimal protein delivery in critically ill children. METHODS: Protein content and
other characteristics of pediatric EN formulas used worldwide were recorded.
Factors associated with achievement of recommended protein delivery and tolerance
of protein-supplemented formulas were recorded prospectively in a cohort of
critically ill children. A range of protein supplement doses was added to 2
standard formulas and water, and the osmolality was recorded by cryoscopy in a
bench experiment. RESULTS: We reviewed 125 formulas used in a multicenter study
including sites from >13 countries. A majority of the EN formulas (73.6%) were
polymeric, with a nonprotein calorie/nitrogen ratio of 182 +/- 66 and protein
content of 3.53 +/- 2.00 g/100 mL. In the cohort of critically ill children,
28.5% achieved protein intake goal within 4 days, with no intolerance. In
addition to optimal protein prescription (P < 0.001), protein supplementation (P
= 0.018) and early EN initiation (P = 0.006) were associated with significantly
higher odds of achieving goal protein intake. Formulas supplemented with up to 8
g/100 mL polymeric protein had osmolality <450 mOsm/kg. CONCLUSIONS: The protein
content of current pediatric formulas may be inadequate to meet the needs of
critically ill children. Protein supplementation of formulas allows early
achievement of goal and is likely to be safe.).
PMID- 29350401
TI - Neurodevelopmental outcome in very preterm and very-low-birthweight infants born
over the past decade: a meta-analytic review.
AB - AIM: The purpose of this systematic review was to provide an up-to-date global
overview of the separate prevalences of motor and cognitive delays and cerebral
palsy (CP) in very preterm (VPT) and very-low-birthweight (VLBW) infants. METHOD:
A comprehensive search was conducted across four databases. Cohort studies
reporting the prevalence of CP and motor or cognitive outcome from 18 months
corrected age until 6 years of VPT or VLBW infants born after 2006 were included.
Pooled prevalences were calculated with random-effects models. RESULTS: Thirty
studies were retained, which included a total of 10 293 infants. The pooled
prevalence of cognitive and motor delays, evaluated with developmental tests, was
estimated at 16.9% (95% confidence interval [CI] 10.4-26.3) and 20.6% (95% CI
13.9-29.4%) respectively. Mild delays were more frequent than moderate-to-severe
delays. Pooled prevalence of CP was estimated to be 6.8% (95% CI 5.5-8.4).
Decreasing gestational age and birthweight resulted in higher prevalences. Lower
pooled prevalences were found with the Third Edition of the Bayley Scales of
Infant Development than with the Second Edition. INTERPRETATION: Even though
neonatal intensive care has improved over recent decades, there is still a wide
range of neurodevelopmental disabilities resulting from VPT and VLBW births.
However, pooled prevalences of CP have diminished over the years. WHAT THIS PAPER
ADDS: The Bayley Scales of Infant and Toddler Development, Third Edition reported
lower pooled prevalences of motor and cognitive delays than the Second Edition.
The pooled prevalence of cerebral palsy in infants born extremely preterm was
reduced compared with previous meta-analyses.
PMID- 29350402
TI - Effectiveness and safety of original and generic sofosbuvir for the treatment of
chronic hepatitis C: A real world study.
AB - We report the first real-world prospective multicenter cohort study that
evaluated the effectiveness and safety of original or generic sofosbuvir-based
regimens in patients with chronic hepatitis C in Latin America. The main
endpoints were assessment of sustained virological response and serious adverse
events rates. A total of 321 patients with chronic hepatitis C treated with the
following regimens were included: sofosbuvir plus daclatasvir for 12 (n = 34) or
24 (n = 135) weeks, sofosbuvir plus daclatasvir plus ribavirin for 12 (n = 84) or
24 (n = 56) weeks, or sofosbuvir plus ribavirin for 12 (n = 8) or 24 (n = 2)
weeks. Patients received either original sofosbuvir (Sovaldi(r) , Gilead
Sciences, n = 135) or generic sofosbuvir (Probirase(r) , Laboratorios RICHMOND, n
= 184) which were randomly assigned by the National Ministry of Health. Overall,
292 (91%) patients had cirrhosis, 136 (42%) were treatment experienced, and 240
(75%) genotype 1. The overall sustained virological response was 90% (95% CI 86
93%); 91% (95% CI 84-95%) in patients who received Sovaldi(r) , and 89% (95% CI
84-93%) in patients who received Probirase(r) . Anemia was the most common
adverse event and was reported in 52 (17%) patients. Bacterial infection,
gastrointestinal bleeding, worsening of ascites or encephalopathy occurred in
less than 5% of the patients. During the study, seven (2%) patients died, four of
whom died of cirrhosis-related complications. In summary, we observed similar
sustained virological response rates than prior studies, both in patients who
received Sovaldi(r) or Probirase(r) . Serious adverse events were infrequent, in
line with prior studies that included patients with cirrhosis treated with
protease-inhibitor-free regimes.
PMID- 29350403
TI - Influence of Contrast Administration on Computed Tomography-Based Analysis of
Visceral Adipose and Skeletal Muscle Tissue in Clear Cell Renal Cell Carcinoma.
AB - BACKGROUND: Computed tomography (CT) scans are being utilized to examine the
influence of skeletal muscle and visceral adipose quantity and quality on health
related outcomes in clinical populations. However, little is known about the
influence of contrast administration on these parameters. METHODS: Precontrast,
arterial, and 3-minute postcontrast CT images of 45 patients with clear cell
renal cell carcinoma were downloaded from The Cancer Imaging Archive and
retrospectively analyzed for visceral adipose cross-sectional area (CSA) and
density, and muscle CSA and density at the third lumbar vertebrae. Low muscle CSA
index was defined as <=38.9 cm2 /m2 for women and <=55.4 cm2 /m2 for men. Low
muscle density was defined as <41 Hounsfield units (HU) for body mass index (BMI)
<24.9 kg/m2 and <33 HU for BMI >=25.0 kg/m2 . RESULTS: In both the arterial and 3
minute phases, contrast administration decreased visceral adipose CSA (-20.9 and
20.9 cm2 ; P < .001) and increased visceral adipose density (4.8 and 5.8 HU; P <
.001), relative to precontrast images. Muscle CSA index marginally increased in
the arterial (0.6 cm2 /m2 ; P = .007) and 3-minute phases (0.8 cm2 /m2 ; P <
.001). This likely represents clinically insignificant changes because it does
not alter the identification of low muscle CSA (44.4% vs 42.2%; P = 1.00).
Skeletal muscle density increased in the arterial (6.4 HU; P < .001) and 3-minute
phases (8.7 HU; P < .001), which altered the identification of low muscle density
(6.7% vs 31.1%; P < .001). CONCLUSIONS: Future analyses should consider the phase
of contrast during CT imaging because it may alter the interpretations of several
parameters.
PMID- 29350404
TI - Gastrointestinal protists and helminths of habituated agile mangabeys (Cercocebus
agilis) at Bai Hokou, Central African Republic.
AB - Infectious diseases including those caused by parasites can be a major threat to
the conservation of endangered species. There is thus a great need for studies
describing parasite infections of these species in the wild. Here we present data
on parasite diversity in an agile mangabey (Cercocebus agilis) group in Bai
Hokou, Dzanga-Sangha Protected Areas (DSPA), Central African Republic. We
coproscopically analyzed 140 mangabey fecal samples by concentration techniques
(flotation and sedimentation). Agile mangabeys hosted a broad diversity of
protistan parasites/commensals, namely amoebas (Entamoeba spp., Iodamoeba
buetschlli), a Buxtonella-like ciliate and several parasitic helminths:
strongylid and spirurid nematodes, Primasubulura sp., Enterobius sp., and
Trichuris sp. Importantly, some of the detected parasite taxa might be of
potential zoonotic importance, such as Entamoeba spp. and the helminths
Enterobius sp., Trichuris sp., and strongylid nematodes. Detailed morphological
examination of ciliate cysts found in mangabeys and comparison with cysts of
Balantioides coli from domestic pigs showed no distinguishing structures,
although significant differences in cyst size were recorded. Scanning or
transmission electron microscopy combined with molecular taxonomy methods are
needed to properly identify these ciliates. Further studies using molecular
epidemiology are warranted to better understand cross-species transmission and
the zoonotic potential of parasites in sympatric non-human primates and humans
cohabiting DSPA.
PMID- 29350406
TI - Cutaneous hyperpigmentation induced by apremilast.
PMID- 29350405
TI - Reactive oxygen species-induced parthanatos of immunocytes by human
cytomegalovirus-associated substance.
AB - Previous studies have examined various immune evasion strategies of human
cytomegalovirus (HCMV) to gain understanding of its pathogenesis. Although the
mechanism that underlies immunocyte destruction near HCMV-infected lesions has
yet to be established, it is here shown that substances produced by HCMV-infected
cells induce death in several types of immunocytes, but not in fibroblasts or
astrocytomas. These substances contain HCMV proteins and were termed HCMV
associated insoluble substance (HCMVAIS). The mechanism by which HCMVAIS induces
cell death was characterized to improve understanding the death of immunocytes
near HCMV-infected lesions. HCMVAIS were found to trigger production of
intracellular nicotinamide adenine dinucleotide phosphate oxidase-derived
reactive oxygen species (ROS), resulting in cell death, this effect being
reversed following treatment with ROS inhibitors. Cell death was not induced in
splenocytes from NOX-2 knockout mice. It was hypothesized that DNA damage induced
by oxidative stress initiates poly ADP-ribose polymerase-1 (PARP-1)-mediated cell
death, or parthanatos. HCMVAIS-induced cell death is accompanied by PARP-1
activation in a caspase-independent manner, nuclear translocation of apoptosis
inducing factor (AIF), and DNA fragmentation, which are typical features of
parthanatos. Treatment with an AIF inhibitor decreased the rate of HCMVAIS
induced cell death, this being confirmed by hematoxylin and eosin staining; cell
death in most HCMV-positive foci in serial section samples of a large intestine
with HCMV infection was TUNEL-positive, cleaved caspase 3-negative and CD45
positive. Taken together, these data suggest that HCMV inhibits local immune
responses via direct killing of immunocytes near HCMV-infected cells through ROS
induced parthanatos by HCMVAIS.
PMID- 29350407
TI - Recent progress in the antiviral activity and mechanism study of pentacyclic
triterpenoids and their derivatives.
AB - Viral infections cause many serious human diseases with high mortality rates. New
drug-resistant strains are continually emerging due to the high viral mutation
rate, which makes it necessary to develop new antiviral agents. Compounds of
plant origin are particularly interesting. The pentacyclic triterpenoids (PTs)
are a diverse class of natural products from plants composed of three terpene
units. They exhibit antitumor, anti-inflammatory, and antiviral activities.
Oleanolic, betulinic, and ursolic acids are representative PTs widely present in
nature with a broad antiviral spectrum. This review focuses on the recent
literatures in the antiviral efficacy of this class of phytochemicals and their
derivatives. In addition, their modes of action are also summarized.
PMID- 29350408
TI - Calibration and non-orthogonality correction of three-axis Hall sensors for the
monitoring of MRI workers' exposure to static magnetic fields.
AB - A Magnetic Resonance Imaging (MRI) scanner uses three different electromagnetic
fields (EMF) to produce body images: a static permanent magnetic field (MF),
several pulsed magnetic gradients, and a radiofrequency pulse. As a result, any
occupation that includes an MRI exposes workers to a strong MF. The World Health
Organization has now given the monitoring of occupational EMF exposure a high
priority. One design for a low-cost, compact MF exposure monitor (" MR
exposimeter ") uses a set of three orthogonally assembled Hall sensors. However,
at such a strong EMF exposure intensity, the non-linearity and non-orthogonality
(misalignment between the three Hall sensors) have an impact on the accuracy of
EMF measurement. Therefore, a sensor characterization was performed in order to
link Hall-effect output voltage to MF intensity. The sensor was then calibrated
using an orthogonalization matrix and an offset vector. For each sensor
configuration, the matrix and vector parameters were optimized with a calibration
set generated by the movement of a three-axis sensor inside homogeneous MF areas.
Once calibrated, the sensor was tested at different MF intensities and returned
accuracy improvements. This calibration procedure was tested on synthetic data
and performed on experimental data. The calibration parameters can be easily
reused by the user, and their stability could be used as a quality control
sensor. Finally, real-time monitoring test for static MF exposure was completed
and validated on an MRI worker during a typical working day. Bioelectromagnetics.
39:108-119, 2018. (c) 2018 Wiley Periodicals, Inc.
PMID- 29350409
TI - Comparison of lesional skin c-KIT mutations with clinical phenotype in patients
with mastocytosis.
AB - BACKGROUND: Activating c-KIT mutations cause abnormal mast cell growth and appear
to play a role in mastocytosis. However, the correlation of c-KIT mutations with
disease phenotypes is poorly characterized. AIM: To evaluate the correlation of c
KIT mutations with clinical presentations and laboratory findings. METHODS: Total
cellular RNA was isolated from the skin lesions of 43 adults and 7 children with
mastocytosis, and PCR amplicons of cDNA were sequenced for c-KIT mutations.
RESULTS: The most common activating mutation, KIT-D816V, was identified in 72% of
adults and 57% of children. Additional activating mutations, namely, V560G and
the internal tandem duplications (ITDs) 502-503dupAY, were detected in 12% of
adults and 8% of children. V560G occurred more commonly in our patients than
previously reported, and it appeared to be associated with more advanced disease.
Otherwise, the presence or absence of activating mutations did not correlate with
skin lesion morphology, disease extent or total serum tryptase levels. Four
adults had expression only of wild-type KIT, while two others had expression of a
truncated KIT lacking tyrosine kinase activity; yet these patients were
clinically indistinguishable from those patients with activating c-KIT mutations.
CONCLUSIONS: Activating c-KIT mutations exist in a significant portion of
patients with mastocytosis, but not all patients showed expression of these
mutations. Except for V560G, the presence or absence of activating c-KIT
mutations did not predict the extent of disease. These observations suggest that
although activating c-KIT mutations are associated with mast cell growth, other
genes probably play a role in the cause of mastocytosis.
PMID- 29350410
TI - Misidentification of recombinant hepatitis C virus leading to treatment failure
with direct acting antivirals.
AB - The use of new Direct Acting Antivirals, specific of HCV, has greatly improved
the HCV treatment. Most of the DAA are specific of HCV genotypes. Genotyping
methods may target different regions of the HCV genome, though only the whole
genome sequencing could confirm the correct genotype. The present study describes
the virological investigation of a treatment failure due to the false
identification of an unusual 2k/1b recombinant HCV form. It describes the
sequencing methods, and the similarity analysis of the sequences to different
genotype query sequences, to identify the recombination breakpoint.
PMID- 29350411
TI - Goals and practicalities of immunoblotting and immunohistochemistry: A guide for
submission to the British Journal of Pharmacology.
PMID- 29350412
TI - Surgical repair of propagating condylar fractures of the third
metacarpal/metatarsal bones with cortical screws placed in lag fashion in 26
racehorses (2007-2015).
AB - BACKGROUND: Despite the recommendation of plate fixation for propagating condylar
fractures of the third metacarpal (McIII) or third metatarsal bone (MtIII), lag
screw fixation can be a viable surgical option. OBJECTIVES: To evaluate short
term outcome and long-term racing performance of horses that underwent lag screw
fixation of long condylar fractures of the McIII/MtIII. STUDY DESIGN:
Retrospective case series. METHODS: Medical records, post-surgical racing
performance and outcome of 26 horses with propagating fractures of the medial
and/or lateral condyle of McIII/MtIII were reviewed. Medical information included
were age, breed, sex, physical examination at admission, circumstances of
fracture, radiographic evaluation, anaesthesia and recovery records, surgical and
post-operative management, as well as complications. Outcome included racing data
and information from telephone interviews. RESULTS: Twenty-six horses (9
Standardbreds and 17 Thoroughbreds) were admitted with a long condylar fracture
of the McIII/MtIII. Fore- and hindlimbs were equally represented with the left
hindlimb being more frequently involved. Most of the fractures had a spiralling
component (76%) and four (15%) were comminuted. Fifteen (58%) horses raced post
surgery including nine Standardbreds (100%) and six Thoroughbreds (35%). Twelve
of them were placed in at least one race and 11 won at least once. One horse
sustained a severe complication in recovery. No significant difference was
observed in the racing performances before and after surgery. MAIN LIMITATIONS:
Follow-up method and duration were not standardised and there is a low number of
cases with six surgeons. CONCLUSIONS: Long condylar fractures can be repaired
using lag fashion technique combined with a half-limb or full-limb tight cast for
recovery as a good surgical alternative. Similar results to plate fixation can be
expected, with a return to racing of more than 50%, and the prognosis being even
better for pacers.
PMID- 29350413
TI - Occupational exposure to extremely low-frequency magnetic fields and the risk of
ALS: A systematic review and meta-analysis.
AB - We performed a meta-analysis to examine associations of occupational exposure to
extremely-low frequency magnetic fields (ELF-MF) with amyotrophic lateral
sclerosis (ALS). Epidemiologic studies were identified in EMBASE and MEDLINE, in
reference lists and a specialist database. We included studies that reported risk
estimates of ALS in association with occupational ELF-MF exposure. Summary
relative risks (RR) or odds ratios (OR) were obtained with random effect meta
analysis, and analyses were stratified by type of exposure assessment. This was
done to evaluate whether observed heterogeneity between studies could be
explained with differences in the way the exposure had been determined. We
included 20 studies in our meta-analysis. Overall, studies reported a slightly
increased risk of ALS in those exposed to higher levels of ELF-MF compared to
lower levels with a summary RR (sRR) of 1.14 (95% Confidence Interval [CI] 1.00
1.30) and for workers in electrical occupations (sRR 1.41, CI 1.05-1.92), but
with large heterogeneity between studies (I2 > 70%). Self-reported exposure or
occupations determined from death certificates did not show increased risks.
Highest-longest types of exposure translated into increased risks of ALS if the
studies had evaluated the whole occupational history, in contrast to evaluating
only few points in time (e.g., from census records); sRR were 1.89 (CI 1.31-2.73,
I2 0%) and 1.06 (CI 0.75-1.57, I2 76%), respectively. In this meta-analysis, we
observed an increased risk of ALS in workers occupationally exposed to ELF-MF.
Results of studies depended on the quality of the exposure assessment.
Bioelectromagnetics. 39:156-163, 2018. (c) 2018 Wiley Periodicals, Inc.
PMID- 29350414
TI - Ross River virus in Australian blood donors: possible implications for blood
transfusion safety.
AB - BACKGROUND: Emerging transfusion-transmissible pathogens, including arboviruses
such as West Nile, Zika, dengue, and Ross River viruses, are potential threats to
transfusion safety. The most prevalent arbovirus in humans in Australia is Ross
River virus (RRV); however, prevalence varies substantially around the country.
Modeling estimated a yearly risk of 8 to 11 potentially RRV-viremic fresh blood
components nationwide. This study aimed to measure the occurrence of RRV viremia
among donors who donated at Australian collection centers located in areas with
significant RRV transmission during one peak season. STUDY DESIGN AND METHODS:
Plasma samples were collected from donors (n = 7500) who donated at the selected
collection centers during one peak season. Viral RNA was extracted from
individual samples, and quantitative reverse transcription-polymerase chain
reaction was performed. RESULTS: Regions with the highest rates of RRV
transmission were not areas where donor centers were located. We did not detect
RRV RNA among 7500 donations collected at the selected centers, resulting in a
zero risk estimate with a one-sided 95% confidence interval of 0 to 1 in 2019
donations. CONCLUSION: Our results suggest that the yearly risk of collecting a
RRV-infected blood donation in Australia is low and is at the lower range of
previous risk modeling. The majority of Australian donor centers were not in
areas known to be at the highest risk for RRV transmission, which was not taken
into account in previous models based on notification data. Therefore, we believe
that the risk of RRV transfusion transmission in Australia is acceptably low and
appropriately managed through existing risk management, including donation
restrictions and recall policies.
PMID- 29350415
TI - Diagnoses and ordering practices driving blood demand for treatment of anemia in
Tanzania.
AB - BACKGROUND: Resource-limited countries in Africa experience blood shortages.
Understanding clinical drivers of blood demand can inform strategies to increase
blood availability. STUDY DESIGN AND METHODS: From a national representative
sample of 42 hospitals in Tanzania, patient records and requests for whole blood
(WB) and red blood cells (RBCs) to treat anemia were analyzed using data
collected prospectively from June through September 2013. Abstracted data
included cause of anemia, number of requested units, clinical signs, and
pretransfusion hemoglobin (Hb) levels. Weighted projections of nationwide drivers
of blood demand for the year, 2013, were calculated. Mean posttransfusion Hb
levels were estimated, and blood requests were assessed for clinical
appropriateness. RESULTS: Malaria was the leading driver of blood demand for
anemia among children, accounting for 67% (55,949 units; standard deviation [SD],
1911 units) of projected units requested for children in 2013. Maternal
hemorrhage was the leading driver of blood demand for anemia among adults,
accounting for 21% (31,321 units; SD, 963 units) of projected units requested.
Seventeen percent (26,133 units; SD, 1013 units) of projected requested units
were deemed inappropriate. Adults with severe anemia had a mean Hb level of 3.7
g/dL and a mean of 1.6 WB or RBC units per request, resulting in an estimated
mean posttransfusion Hb level of 5.3 g/dL. CONCLUSIONS: Strategies to prevent and
treat underlying causes of anemia and decrease inappropriate blood requests will
likely increase blood availability. Restrictive blood ordering practices seen in
adults with severe anemia suggests undertreatment of anemia and may result in an
underestimation of the national blood demand.
PMID- 29350416
TI - Acute hemorrhagic lesions in an immunosuppressed patient.
PMID- 29350417
TI - Hepatitis C virus core protein induces dysfunction of liver sinusoidal
endothelial cell by down-regulation of silent information regulator 1.
AB - Hepatic fibrosis is a frequent feature of chronic hepatitis C virus (HCV)
infection. Some evidence has suggested the potential role of silent information
regulator 1 (SIRT1) in organ fibrosis. The aim of this study was to investigate
the effect of HCV core protein on expression of SIRT1 of liver sinusoidal
endothelial cell (LSEC) and function of LSEC. LSECs were co-cultured with HepG2
cells or HepG2 cells expressing HCV core protein and LSECs cultured alone were
used as controls. After co-culture, the activity and expression levels of mRNA
and protein of SIRT1 in LSEC were detected by a SIRT1 fluorometric assay kit,
real time-PCR (RT-PCR), Western blot, respectively. The levels of adiponectin
receptor 2 (AdipoR2), endothelial nitric oxide synthase (eNOS) and vascular
endothelial growth factor (VEGF) were measured by Western blot. Cluster of
differentiation 31 (CD31), CD14, and von Willebrand factor (vWf) of LSECs was
performed by flow cytometry. The level of reactive oxygen species (ROS) was
assayed. Malondialdehyde (MDA), superoxide dismutase (SOD), adiponectin, nitric
oxide (NO), and endothelin-1 (ET-1) levels in the co-culture supernatant were
measured. The co-culture supernatant was then used to cultivate LX-2 cells. The
levels of alpha-smooth muscle actin (ASMA) and transforming growth factor-beta1
(TGF-beta1) protein in LX-2 cells were measured by Western blot. Compared with
LSEC co-cultured with HepG2 cells group, in LSEC co-cultured with HepG2-core
cells group, the activity and expression level of mRNA and protein of SIRT1
reduced; the level of adiponectin reduced and the expression level of AdipoR2
protein decreased; ROS levels increased; the expression level of eNOS, VEGF
protein decreased; and the expression level of CD14 decreased; the expression
level of vWf and CD31 increased; NO and SOD levels decreased; whereas ET-1 and
MDA levels increased; the levels of ASMA and TGF-beta1 protein in LX-2 cells
increased. SIRT1 activator improved the above-mentioned changes. HCV core protein
may down-regulate the activity and the expression of SIRT1 of LSEC, then
decreasing synthesis of adiponectin and the expression of AdipoR2, thus inducing
contraction of LSEC and hepatic sinusoidal capillarization and increasing
oxidative stress, ultimately cause hepatic stellate cell (HSC) activation.
Treatment with SIRT1 activator restored the function of LSEC and inhibited the
activation of HSC.
PMID- 29350418
TI - Species differences in circulation and inflammatory responses in children with
common respiratory adenovirus infections.
AB - Human adenoviruses (HAdVs) cause severe inflammatory respiratory infections, but
previous epidemiological studies lacked analysis of the characteristics of the
inflammation. Consecutive patients <13 years old with acute febrile illness
during a 2-year period were tested. HAdV strains were isolated from
nasopharyngeal swabs, and molecular identification was performed by hexon, fiber,
and species-specific PCR methods. Blood inflammatory markers, including the white
blood cell (WBC) count, CRP, and 29 cytokines, were measured. A total of 187
patients were enrolled, and HAdV types were identified from 175 patients (93.5%).
Species C (types 2, 1, 5, and 6, in order of frequency) was most common at 37.1%,
followed by B (type 3) at 30.9% and E (type 4) at 26.9%. Species C was detected
predominantly in 1-year-old, whereas B and E were in older ages. Species C and B
had seasonal circulation patterns, but E was found in only one season during the
2-year study period. The WBC count was highest in patients with species C. Eleven
of the 29 tested serum cytokines were detected. Seven kinds, including G-CSF, IL
6, and TNF-alpha, were elevated in species C infections, whereas IL-10 was lowest
in species C. Species differences in inflammatory responses, especially regarding
serum cytokines were described in common pediatric HAdV infections. Species C
causes the strongest inflammatory responses in young children.
PMID- 29350420
TI - Over-expression of DEC1 inhibits myogenic differentiation by modulating MyoG
activity in bovine satellite cell.
AB - Differentiated embryo chondrocyte 1 (DEC1), a member of basic-helix-loop-helix
transcription factor Bhlhe40, also called stimulated by retinoic acid 13, STRA13,
plays an important role in the regulation of adipogenesis, tumorigenesis,
peripheral circadian output, response to hypoxia, and development of metabolic
syndrome. Previous studies suggested that DEC1 was involved in skeletal muscle
development; however, its precise role in myoblast differentiation has not been
determined. In the present study, we showed that DEC1 expressed ubiquitously in
different bovine tissues and was down-regulated in differentiated bovine
satellite cells. Expression of muscle specific transcription factors (Myf5, MyoD,
MyoG, and MHC) was significantly down-regulated when DEC1 was over-expressed by
both CoCl2 -simulated hypoxia and Adenovirus-mediated transduction in bovine
satellite cells. Consistent with that, promoter analyses via luciferase reporter
assay also revealed that overexpression of bovine DEC1 could inhibit MyoG
promoter activity. In conclusion, overexpression of DEC1 blocked myogenesis by
inhibiting MyoG promoter activity in bovine. Our results provided a new mechanism
for the muscle growth, which would contribute to increase cattle meat
productivity.
PMID- 29350421
TI - Involvement of xanthine oxidase inhibition with the antioxidant property of
nanoencapsulated Melaleuca alternifolia essential oil in fish experimentally
infected with Pseudomonas aeruginosa.
AB - Nanoencapsulated Melaleuca alternifolia essential oil (tea tree oil, TTO) is a
natural alternative treatment, with 100% therapeutic efficacy in fish
experimentally infected with Pseudomonas aeruginosa, and has also potent
protective effects linked with antioxidant properties. However, the pathways
responsible for the antioxidant capacity remain unknown. Thus, this study
evaluated whether the inhibition of seric xanthine oxidase (XO) activity can be
considered a pathway involved in the antioxidant capacity of nanoencapsulated TTO
in fish experimentally infected with P. aeruginosa. Seric samples from fish
infected with P. aeruginosa showed increased XO activity, as well as increased
uric acid and reactive oxygen species (ROS) levels. In contrast, the prophylactic
treatment with nanoencapsulated TTO prevented these infection-induced
alterations. Based on the evidence obtained, the upregulation of seric XO
activity induced pro-oxidative effects in the serum of fish experimentally
infected with P. aeruginosa, due to excessive formation of uric acid, which
stimulates the release of ROS. This treatment was able to prevent the upregulated
seric XO activity and, consequently, the excessive formation of uric acid and
ROS. In summary, inhibition of seric XO activity can be considered a pathway
involved in the antioxidant capacity of nanoencapsulated TTO in fish
experimentally infected with P. aeruginosa.
PMID- 29350419
TI - An integrated framework for the role of oxytocin in multistage social decision
making.
AB - Interest in the effects of oxytocin on social behavior has persisted even as an
overarching theory describing these effects has remained largely elusive. Some of
the earliest studies on the effects of oxytocin on social decision-making
indicated that oxytocin might enhance prosocial actions directed toward others.
This led to development of the prosocial hypothesis, which stipulates that
oxytocin specifically enhances prosocial choices. However, further work indicated
that oxytocin administration could elicit antisocial behaviors as well in certain
social situations, highlighting the importance of context-dependent effects. At
least two prominent hypotheses have been used to explain these seemingly
contradictory findings. The social salience hypothesis indicates that the effects
of oxytocin can be conceptualized as a general increase in the salience of social
stimuli in the environment. Distinctly, the approach/withdrawal hypothesis
stipulates that oxytocin enhances approach behaviors and decreases withdrawal
behaviors. These phenomenologically motivated hypotheses regarding the effects of
oxytocin on social behavior have created controversies in the field. In this
review, we present a multistage framework of social decision-making designed to
unify these disparate theories in a process common to all social decisions. We
conceptualize this process as involving multiple distinct computational steps,
including sensory input, sensory perception, valuation, decision formulation, and
behavioral output. Iteratively, these steps generate social behaviors, and
oxytocin could be acting on any of these steps to exert its effects. In support
of this framework, we examine both behavioral and neural evidence across rodents,
non-human primates, and humans, determining at what point in our multistage
framework oxytocin could be eliciting its socially relevant effects. Finally, we
postulate based on our framework that the prosocial, social salience, and
approach/withdrawal hypotheses may not be mutually exclusive and could explain
the influence of oxytocin on social behavior to different extents depending on
context.
PMID- 29350422
TI - Potency of polycyclic aromatic hydrocarbons in chicken and Japanese quail
embryos.
AB - Birds are receptors of concern for polycyclic aromatic hydrocarbons (PAHs), yet
limited data describing the relative potency of PAH congeners are available for
avian species. In the present study, we determined embryonic median lethal dose
(LD50) values for 5 PAH congeners in chicken (Gallus gallus) and one PAH congener
in Japanese quail (Coturnix japonica). Graded concentrations of each test
compound were injected into the air cell of chicken or quail eggs before
incubation. Embryos were monitored through development (quail) or hatching
(chicken). All PAHs tested caused dose-dependent increases in embryo mortality,
but few other effects (e.g., weight changes, deformities) were observed. In
chicken, windows of developmental sensitivity were identified between embryonic
days 4 and 9 and between embryonic days 20 and 22. The rank order potency of
benzo[k]fluoranthene (BkF; 76 MUg/kg) ~ dibenz[ah]anthracene (83 MUg/kg) >
indeno[1,2,3-cd]pyrene (325 MUg/kg) > benzo[a]pyrene (461 MUg/kg) >
benz[a]anthracene (529 MUg/kg) corresponded well with previous in vitro estimates
in birds. Previously published ethoxyresorufin-O-deethylase median effect
concentrations from cultured chicken embryo hepatocytes were highly predictive of
our LD50s (p < 0.001, r2 = 0.99). To explore differences in sensitivity between
species, Japanese quail eggs were injected with BkF, the most potent PAH. We
found that chicken and quail were nearly equally sensitive to BkF. The present
results contribute to our developing understanding of variability in responses to
PAHs among congeners and species. Environ Toxicol Chem 2018;37:1556-1564. (c)
2018 SETAC.
PMID- 29350423
TI - Ephrin-A1-EphA4 signaling negatively regulates myelination in the central nervous
system.
AB - During development of the central nervous system not all axons are myelinated,
and axons may have distinct myelination patterns. Furthermore, the number of
myelin sheaths formed by each oligodendrocyte is highly variable. However, our
current knowledge about the axo-glia communication that regulates the formation
of myelin sheaths spatially and temporally is limited. By using axon-mimicking
microfibers and a zebrafish model system, we show that axonal ephrin-A1 inhibits
myelination. Ephrin-A1 interacts with EphA4 to activate the ephexin1-RhoA-Rock
myosin 2 signaling cascade and causes inhibition of oligodendrocyte process
extension. Both in myelinating co-cultures and in zebrafish larvae, activation of
EphA4 decreases myelination, whereas myelination is increased by inhibition of
EphA4 signaling at different levels of the pathway, or by receptor knockdown.
Mechanistically, the enhanced myelination is a result of a higher number of
myelin sheaths formed by each oligodendrocyte, not an increased number of mature
cells. Thus, we have identified EphA4 and ephrin-A1 as novel negative regulators
of myelination. Our data suggest that activation of an EphA4-RhoA pathway in
oligodendrocytes by axonal ephrin-A1 inhibits stable axo-glia interaction
required for generating a myelin sheath.
PMID- 29350424
TI - Prevalence of high-grade cervical intraepithelial neoplasia in women with
persistent high-risk HPV genotypes and negative cytology.
AB - INTRODUCTION: Primary HPV screening will be implemented into the English Cervical
Screening Programme by 2019. Its impact upon women referred to colposcopy, with
negative cytology but persistently positive high-risk HPV (hrHPV), remains
unreported from UK Sentinel sites. HPV primary screening was introduced in
Sheffield, UK in April 2013; this paper reports its impact on the service.
METHODS: A retrospective cohort study was performed from June 2014 to July 2016
at the Jessop Wing Colposcopy Unit, Sheffield. UK. Data were obtained from the
pathology and colposcopy databases and cross-referenced with case-notes and
pathology results for women referred with persistently positive hrHPV, cytology
negative samples. Patient demographics, hrHPV genotype, biopsy rates,
histological diagnoses, management, and outcomes were collected and baseline
statistics performed. RESULTS: During the study 1076 women were seen. Most
frequent hrHPV genotypes were: hrHPV other, 41%; and HPV16, 33%. The majority
(72%) were found to have normal colposcopy; 28% had an abnormal colposcopic
assessment (11% low-grade; 11% high-grade; 6% inadequate). The majority were
discharged (83%) and only 5% underwent LLETZ. No cancers were detected. High
grade cervical intraepithelial neoplasia (CIN) was found in 7%; overall risk of
CIN2 was 1/29; 1/30 for CIN3. Presence of HPV16 was associated with a
significantly higher risk of high-grade CIN; 1/9. CONCLUSION: This is the first
study to report results for women referred to colposcopy with cytology negative,
persistently positive hrHPV. Disease prevalence is low, although women with HPV16
have a significantly higher likelihood of high-grade disease compared to other
HPV subtypes.
PMID- 29350426
TI - Efficacy of photodynamic therapy in the treatment of symptomatic oral lichen
planus: A systematic review.
AB - BACKGROUND: The aim of this study was to systematically review the efficacy of
photodynamic therapy (PDT) in the management of symptomatic oral lichen planus
(OLP). MATERIALS AND METHODS: PubMed/MEDLINE, Scopus, and ISI Web of knowledge
were searched until July 2017, using the following keywords: OLP, erosive lichen
planus, lichen planus, and PDT. RESULTS: Five clinical studies were included. The
risk of bias was considered high in 4 studies and moderate in 1 study. The
efficacy of PDT was compared with topical corticosteroids in all included
studies. Laser wavelengths, duration of irradiation, and power density ranged
between 420-660 nm, 30 seconds to 10 minutes, and 10-500 mW/cm2 , respectively.
All studies reported PDT to be effective in the management of symptomatic OLP.
Two studies reported PDT to be as effective as corticosteroids, 1 study reported
a better efficacy of PDT compared to corticosteroids, whereas 2 studies found PDT
to be inferior to corticosteroids. CONCLUSIONS: The limited available evidence
suggests that PDT is an effective treatment option for the management of OLP.
However, due to the limited number of studies included in this review and
heterogeneity among these studies, more well-designed clinical trials with
adequate sample sizes are highly warranted.
PMID- 29350425
TI - The impact of preapheresis white blood cell count on autologous peripheral blood
stem cell collection efficiency and HSC infusion side effect rate.
AB - BACKGROUND: Autologous peripheral blood hematopoietic stem cell (PBSC) collection
efficiency (CE) is reportedly affected by the patient's blood properties;
however, studies to identify factors correlated with CE have shown inconsistent
results. Additionally, variables such as stem cell graft granulocyte content and
patient age, sex, and underlying disease, may be associated with hematopietic
stem cell (HSC) infusion-related adverse reactions. In this study, we evaluated
the correlation of preleukapheresis PB granulocyte count and PBSC harvest
variables with CD34+ collection yield and efficiency, and thawed HSC infusion
side effect occurrence. PATIENTS AND METHODS: We evaluated data from 361 patients
who had undergone autologous PBSC transplant. Large volume leukapheresis was the
method for PBSC collection. Complete Blood Count and CD34+ cell enumeration were
performed in the preapheresis PB and the apheresis product sample. The PBSC
grafts were submitted to non-controlled rate freezing after addition of 5% DMSO
plus 6% hidroxyethylstarch as a cryoprotectant solution. The cryopreserved graft
was thawed in a 37 degrees C water bath and then infused without further
manipulation. RESULTS: The CD34+ yield was associated with preapheresis PB CD34+
count and immature granulocyte count. The PBSC CE was negatively correlated with
preapheresis white blood cell (WBC), immature granulocyte and granulocyte count.
The leukapheresis product total nucleated cell (TNC) and granulocyte content was
correlated with the thawed graft infusion side effect occurrence. CONCLUSION:
This study has shown that preapheresis PB WBC and granulocyte counts were
associated with leukapheresis CE. Additionally, the leukapheresis product TNC and
granulocyte content was correlated with thawed graft infusion side effect
occurrence.
PMID- 29350427
TI - Role of microglia in the spinal cord in colon-to-bladder neural crosstalk in a
rat model of colitis.
AB - AIMS: We investigated whether spinal cord microglia are involved in colon-to
bladder neural crosstalk in a rat model of colitis. METHODS: Adult female SD rats
were divided into A) control, B) colitis, and C) colitis + minocycline groups.
Experimental colitis was induced by administering 50% trinitrobenzene sulfonic
acid into the distal colon in the colitis group and the minocycline group.
Minocycline, a microglial inhibitor, was continuously infused into the
intrathecal space in the minocycline group. The following investigations were
performed on day 7: (1) continuous cystometry (CMG) in an awake condition; (2)
nociceptive behavior observation induced by intravesical instillation of
resiniferatoxin; (3) toluidine blue staining in the bladder; (4)
Immunofluorescence staining for the microglial marker, CD11b, in L6 spinal cord
sections; and (5) quantitative RT-PCR to investigate interleukin-1beta (IL
1beta), chemokine ligand 3 (CCL3), and brain-derived neurotrophic factor (BDNF)
gene expression in the L6 spinal cord. RESULTS: In comparison with the control
group, the colitis group showed significant increases in (1) micturition
frequency during cystometry; (2) resiniferatoxin-induced freezing behavior
(bladder pain); (3) the number of total and degranulated mast cells in the
bladder; (4) the number of microglia in the L6 spinal cord, and (5) the
expression of IL-1beta, CCL3, and BDNF mRNA in the L6 spinal cord. Moreover,
intrathecal administration of minocycline alleviated these pathophysiological
findings caused by experimental colitis. CONCLUSIONS: Spinal microglia may play
an important role in colitis-induced bladder overactivity and enhanced bladder
pain sensitivity in colitis rats.
PMID- 29350428
TI - Meta-analysis of fish early life stage tests-Association of toxic ratios and
acute-to-chronic ratios with modes of action.
AB - Fish early life stage (ELS) tests (Organisation for Economic Co-operation and
Development test guideline 210) are widely conducted to estimate chronic fish
toxicity. In these tests, fish are exposed from the embryonic to the juvenile
life stages. To analyze whether certain modes of action are related to high toxic
ratios (i.e., ratios between baseline toxicity and experimental effect) and/or
acute-to-chronic ratios (ACRs) in the fish ELS test, effect concentrations (ECs)
for 183 compounds were extracted from the US Environmental Protection Agency's
ecotoxicity database. Analysis of ECs of narcotic compounds indicated that
baseline toxicity could be observed in the fish ELS test at similar
concentrations as in the acute fish toxicity test. All nonnarcotic modes of
action were associated with higher toxic ratios, with median values ranging from
4 to 9.3 * 104 (uncoupling < reactivity < neuromuscular toxicity < methemoglobin
formation < endocrine disruption < extracellular matrix formation inhibition).
Four modes of action were also found to be associated with high ACRs: 1) lysyl
oxidase inhibition leading to notochord distortion, 2) putative methemoglobin
formation or hemolytic anemia, 3) endocrine disruption, and 4) compounds with
neuromuscular toxicity. For the prediction of ECs in the fish ELS test with
alternative test systems, endpoints targeted to the modes of action of compounds
with enhanced toxic ratios or ACRs could be used to trigger fish ELS tests or
even replace these tests. Environ Toxicol Chem 2018;37:955-969. (c) 2018 SETAC.
PMID- 29350429
TI - Sprint performance and propulsion asymmetries on an ergometer in trained high-
and low-point wheelchair rugby players.
AB - The purpose of this study was to examine the propulsion asymmetries of wheelchair
athletes while sprinting on an instrumented, dual-roller ergometer system.
Eighteen experienced wheelchair rugby players (8 low point (LP) (class <=1.5) and
10 high point (HP) (class >=2.0)) performed a 15-second sprint in their sports
wheelchair on the instrumented ergometer. Asymmetry was defined as the difference
in distance and power output (PO) between left and right sides when the best side
reached 28 m. Propulsion techniques were quantified based on torque and velocity
data. HP players covered an average 3 m further than the LP players (P = .002)
and achieved faster sprint times than LP players (6.95 +/- 0.89 vs 8.03 +/- 0.68
seconds, P = .005) and at the time the best player finished (5.96 seconds).
Higher peak POs (667 +/- 108 vs 357 +/- 78 W, P = .0001) and greater peak speeds
that were also evident were for HP players (4.80 +/- 0.71 vs 4.09 +/- 0.45 m/s, P
= .011). Greater asymmetries were found in HP players for distance (1.86 +/- 1.43
vs 0.70 +/- 0.65 m, P = .016), absolute peak PO (P = .049), and speed (0.35 +/-
0.25 vs 0.11 +/- 0.10 m/s, P = .009). Although HP players had faster sprint times
over 28 m (achieved by a higher PO), high standard deviations show the
heterogeneity within the two groups (eg, some LP players were better than HP
players). Quantification of asymmetries is important not only for classifiers but
also for sports practitioners wishing to improve performance as they could be
addressed through training and/or wheelchair configuration.
PMID- 29350430
TI - On the impact of sample size on median lethal concentration estimation in acute
fish toxicity testing: Is n = 7/group enough?
AB - The fish acute toxicity test method is foundational to aquatic toxicity testing
strategies, yet the literature lacks a concise sample size assessment. Although
various sources address sample size, historical precedent seems to play a larger
role than objective measures. We present a novel and comprehensive quantification
of the effect of sample size on estimation of the median lethal concentration
(LC50), covering a wide range of scenarios. The results put into perspective the
practical differences across a range of sample sizes, from n = 5/concentration up
to n = 23/concentration. We also provide a framework for setting sample size
guidance illustrating ways to quantify the performance of LC50 estimation, which
can be used to set sample size guidance given reasonably difficult (or worst
case) scenarios. There is a clear benefit to larger sample size studies: they
reduce error in the determination of LC50s, and lead to more robust safe
environmental concentration determinations, particularly in cases likely to be
called worst-case (shallow slope and true LC50 near the edges of the
concentration range). Given that the use of well-justified sample sizes is
crucial to reducing uncertainty in toxicity estimates, these results lead us to
recommend a reconsideration of the current de minimis 7/concentration sample size
for critical studies (e.g., studies needed for a chemical registration, which are
being tested for the first time, or involving difficult test substances). Environ
Toxicol Chem 2018;37:1565-1578. (c) 2018 SETAC.
PMID- 29350431
TI - miFAST: A novel and rapid microRNA target capture method.
AB - MicroRNAs (miRNAs), small 22-25 nucleotide non-coding RNAs, play important roles
in cellular and tumor biology. However, characterizing miRNA function remains
challenging due to an abundance of predicted targets and an experimental
bottleneck in identifying biologically relevant direct targets. Here, we
developed a novel technique (miFAST) to identify direct miRNA target genes. Using
miFAST, we confirmed several previously reported miR-340 target genes and
identified five additional novel direct miR-340 targets in melanoma cells. This
methodology can also be efficiently applied for the global characterization of
miRNA targets. Utilizing miFAST to characterize direct miRNA targetomes will
further our understanding of miRNA biology and function.
PMID- 29350432
TI - National Public Health Data Systems in the United States: Applications to Child
Agricultural Injury Surveillance.
AB - PURPOSE: The United States has no comprehensive national surveillance system for
fatal or nonfatal child agricultural injuries. Thus, important knowledge gaps
exist about recurrent injury patterns that could provide targeted focus for
prevention efforts. The purpose of this study was to explore existing US public
health data systems to determine their utility with respect to informing child
agricultural injury surveillance and primary prevention. METHODS: Public health
data systems were selected if they: (1) were national in scope, (2) were active
and ongoing, (3) included physical injuries, and (4) contained a "farm" location
variable. Data systems explored included National Emergency Medical Services
Information System, National Trauma Data Bank, National Electronic Injury
Surveillance System-All Injury Program, and National Vital Statistics System
Multiple Cause File. FINDINGS: Each data system contained substantial information
per case with the number of fields ranging from 77 to 127. Beyond basic
demographic information about the injured child, there were many injury
descriptors, but few commonalities across systems. The most striking finding was
the uniform absence of information on injury circumstances; that is, why and how
the injury occurred, which is fundamental to planning and evaluating prevention
initiatives. CONCLUSIONS: Although these public health data systems captured many
details regarding medical aspects of the injury, they included little information
on circumstances leading to injury, thus limiting their utility for child
agricultural injury surveillance and primary prevention initiatives. We recommend
any child agricultural injury data collection tool formally incorporate a
structured narrative so underlying circumstances leading to injury events are
documented.
PMID- 29350433
TI - Amino group of salicylic acid exhibits enhanced inhibitory potential against
insulin amyloid fibrillation with protective aptitude toward amyloid induced
cytotoxicity.
AB - Protein misfolding and aggregation lead to amyloid generation that in turn may
induce cell membrane disruption and leads to cell apoptosis. In an effort to
prevent or treat amyloidogenesis, large number of studies has been paying
attention on breakthrough of amyloid inhibitors. In the present work, we aim to
access the effect of two drugs, that is, acetylsalicylic acid and 5-amino
salicylic acid on insulin amyloids by using various biophysical, imaging, cell
viability assay, and computational approaches. We established that both drugs
reduce the turbidity, light scattering and fluorescence intensity of amyloid
indicator dye thioflavin T. Premixing of drugs with insulin inhibited the
nucleation phase and inhibitory potential was boosted by increasing the
concentration of the drug. Moreover, addition of drugs at the studied
concentrations attenuated the insulin fibril induced cytotoxicity in breast
cancer cell line MDA-MB-231. Our results highlight the amino group of salicylic
acid exhibited enhanced inhibitory effects on insulin fibrillation in comparison
to acetyl group. It may be due to presence of amino group that helps it to
prolong the nucleation phase with strong binding as well as disruption of
aromatic and hydrophobic stacking that plays a key role in amyloid progression.
PMID- 29350434
TI - The cystine-glutamate exchanger (xCT, Slc7a11) is expressed in significant
concentrations in a subpopulation of astrocytes in the mouse brain.
AB - : The cystine-glutamate exchanger (xCT) promotes glutathione synthesis by
catalyzing cystine uptake and glutamate release. The released glutamate may
modulate normal neural signaling and contribute to excitotoxicity in pathological
situations. Uncertainty, however, remains as neither the expression levels nor
the distribution of xCT have been unambiguously determined. In fact, xCT has been
reported in astrocytes, neurons, oligodendrocytes and microglia, but most of the
information derives from cell cultures. Here, we show by immunohistochemistry and
by Western blotting that xCT is widely expressed in the central nervous system of
both sexes. The labeling specificity was validated using tissue from xCT knockout
mice as controls. Astrocytes were selectively labeled, but showed greatly varying
labeling intensities. This astroglial heterogeneity resulted in an astrocyte
domain-like labeling pattern. Strong xCT labeling was also found in the
leptomeninges, along some blood vessels, in selected circumventricular organs and
in a subpopulation of tanycytes residing the lateral walls of the ventral third
ventricle. Neurons, oligodendrocytes and resting microglia, as well as reactive
microglia induced by glutamine synthetase deficiency, were unlabeled. The
concentration of xCT protein in hippocampus was compared with that of the EAAT3
glutamate transporter by immunoblotting using a chimeric xCT-EAAT3 protein to
normalize xCT and EAAT3 labeling intensities. The immunoblots suggested an
xCT/EAAT3 ratio close to one (0.75 +/- 0.07; average +/- SEM; n = 4) in adult
C57BL6 mice. CONCLUSIONS: xCT is present in select blood/brain/CSF interface
areas and in an astrocyte subpopulation, in sufficient quantities to support the
notion that system xc- provides physiologically relevant transport activity.
PMID- 29350435
TI - From micro- to macro-structures in multiple sclerosis: what is the added value of
diffusion imaging.
AB - Diffusion imaging has been instrumental in understanding damage to the central
nervous system as a result of its sensitivity to microstructural changes.
Clinical applications of diffusion imaging have grown exponentially over the past
couple of decades in many neurological and neurodegenerative diseases, such as
multiple sclerosis (MS). For several reasons, MS has been extensively researched
using advanced neuroimaging techniques, which makes it an 'example disease' to
illustrate the potential of diffusion imaging for clinical applications. In
addition, MS pathology is characterized by several key processes competing with
each other, such as inflammation, demyelination, remyelination, gliosis and
axonal loss, enabling the specificity of diffusion to be challenged. In this
review, we describe how diffusion imaging can be exploited to investigate micro-,
meso- and macro-scale properties of the brain structure and discuss how they are
affected by different pathological substrates. Conclusions from the literature
are that larger studies are needed to confirm the exciting results from initial
investigations before current trends in diffusion imaging can be translated to
the neurology clinic. Also, for a comprehensive understanding of pathological
processes, it is essential to take a multiple-level approach, in which
information at the micro-, meso- and macroscopic scales is fully integrated.
PMID- 29350436
TI - Age difference between parents influences parity and number of sons.
AB - OBJECTIVES: Among couples, women usually prefer slightly older men, and men tend
to choose much younger partners. Age difference between partners has been shown
to influence their parity; however, results of previous studies are inconsistent.
This study analyzed relationships between husband and wife age difference and
their total number of children, and number of daughters and sons in a
contemporary, rural Polish population. METHODS: Demographic and reproductive data
were collected from 384 postmenopausal women from rural Poland who were married
only once. Regression models were used to evaluate the impact of the age gap
between partners on total number of children and on number of daughters and sons.
Women's age, age at marriage (as an indicator of reproductive value), and years
of education were used in analyzes as potential confounders. RESULTS: There was
an inverted U-shape association between parental age difference and number of
children and also the number of sons. The highest number of children and sons was
observed when men were approximately 6.5 years older than their wives. There was
no significant relationship between parental age difference and number of
daughters. CONCLUSIONS: Age difference between partners is important for
reproductive success (with younger wives having higher reproductive potential)
and is also related to number of sons. Older husbands might provide more
resources for the family, thus facilitating production of well-nourished male
offspring. Future research should evaluate not only number of children but also
their biological condition, health, and lifetime achievements in relation to the
age difference between their parents.
PMID- 29350437
TI - Diffusion tensor imaging MRI of sickle cell kidney disease: initial results and
comparison with iron deposition.
AB - Chronic kidney disease (CKD) occurs in over one-third of patients with sickle
cell disease (SCD) and can progress to end-stage renal disease. Unfortunately,
current clinical assessments of kidney function are insensitive to early-stage
CKD. Previous studies have shown that diffusion magnetic resonance imaging (MRI)
can sensitively detect regional renal microstructural changes associated with
early-stage CKD. However, previous MRI studies in patients with SCD have been
largely limited to the detection of renal iron deposition assessed by T2 *
relaxometry. In this pilot imaging study, we compare MRI assessments of renal
microstructure (diffusion) and iron deposition (T2 *) in patients with SCD and in
non-SCD control subjects. Diffusion tensor imaging (DTI) and T2 * relaxometry MRI
data were obtained for pediatric (n = 5) and adult (n = 4) patients with SCD, as
well as for non-SCD control subjects (n = 10), on a Siemens Espree 1.5-T MRI
scanner. A region-of-interest analysis was used to calculate mean medullary and
cortical values for each MRI metric. MRI findings were also compared with
clinical assessments of renal function and hemolysis. Patients with SCD showed a
significant decrease in medullary fractional anisotropy (FA, p = 0.0001) in
comparison with non-SCD subjects, indicative of microstructural alterations in
the renal medulla of patients with SCD. Cortical and medullary reductions in T2 *
(increased iron deposition, p = <=0.0001) were also observed. Significant
correlations were also observed between kidney T2 * assessments and multiple
measures of hemolysis. This is the first DTI MRI study of patients with SCD to
demonstrate reductions in medullary FA despite no overt CKD [estimated glomerular
filtration rate (eGFR) > 100 mL/min/1.73 m2 ]. These medullary FA changes are
consistent with previous studies in patients with CKD, and suggest that DTI MRI
can provide a useful measure of kidney injury to complement MRI assessments of
iron deposition.
PMID- 29350439
TI - Tandem mass spectroscopy as a tool for investigation of complexes of PNP-lariat
ether derivative with metal ions.
AB - The novel PNP-lariat ether L with cyclotriphosphazene ring incorporated in the
macrocyclic structure was synthesized and checked by the electrospray mass
spectrometry (ESI-MS) method for the ability to bind different types of ions Ag+
, Ca2+ , Cd2+ , Cu2+ , and Pb2+ . Furthermore, the stability constants of the
abovementioned ion complexes with the investigated ligand have been determined by
direct and competitive potentiometric methods. To evaluate the stability of
various complex types and to confirm the way of metal cation binding, the tandem
mass spectra of the investigated ligand and its complexes were taken. As a
result, we obtained quite a good relationship between the number and main types
of complex species observed in ESI-MS experiments and the forms of complexes for
which the stabilization constants were determined by potentiometric methods.
Moreover, we also concluded that in case of big discrepancies of stability
constants, ESI-MS experiments could provide information about the most stable
form of the complexes, but they fail when the differences between the strength of
the coordination binding are slightly different.
PMID- 29350438
TI - Astrocytic glutamine synthetase is expressed in the neuronal somatic layers and
down-regulated proportionally to neuronal loss in the human epileptic
hippocampus.
AB - Human mesial temporal lobe epilepsy (MTLE) features subregion-specific
hippocampal neurodegeneration and reactive astrogliosis, including up-regulation
of the glial fibrillary acidic protein (GFAP) and down-regulation of glutamine
synthetase (GS). However, the regional astrocytic expression pattern of GFAP and
GS upon MTLE-associated neurodegeneration still remains elusive. We assessed GFAP
and GS expression in strict correlation with the local neuronal number in
cortical and hippocampal surgical specimens from 16 MTLE patients using
immunohistochemistry, stereology and high-resolution image analysis for digital
pathology and whole-slide imaging. In the cortex, GS-positive (GS+) astrocytes
are dominant in all neuronal layers, with a neuron to GS+ cell ratio of 2:1. GFAP
positive (GFAP+) cells are widely spaced, with a GS+ to GFAP+ cell ratio of 3:1
5:1. White matter astrocytes, on the contrary, express mainly GFAP and, to a
lesser extent, GS. In the hippocampus, the neuron to GS+ cell ratio is
approximately 1:1. Hippocampal degeneration is associated with a reduction of GS+
astrocytes, which is proportional to the degree of neuronal loss and primarily
present in the hilus. Up-regulation of GFAP as a classical hallmark of reactive
astrogliosis does not follow the GS-pattern and is prominent in the CA1. Reactive
alterations were proportional to the neuronal loss in the neuronal somatic layers
(stratum pyramidale and hilus), while observed to a lesser extent in the
axonal/dendritic layers (stratum radiatum, molecular layer). We conclude that
astrocytic GS is expressed in the neuronal somatic layers and, upon
neurodegeneration, is down-regulated proportionally to the degree of neuronal
loss.
PMID- 29350440
TI - Abrupt burial imparts persistent changes to the bacterial diversity of turbidite
associated sediment profiles.
AB - The emplacement of subaqueous gravity-driven sediment flows imposes a significant
physical and geochemical impact on underlying sediment and microbial communities.
Although previous studies have established lasting mineralogical and biological
signatures of turbidite deposition, the response of bacteria and archaea within
and beneath debris flows remains poorly constrained. Both bacterial cells
associated with the underlying sediment and those attached to allochthonous
material must respond to substantially altered environmental conditions and
selective pressures. As a consequence, turbidites and underlying sediments
provide an exceptional opportunity to examine (i) the microbial community
response to rapid sedimentation and (ii) the preservation and identification of
displaced micro-organisms. We collected Illumina MiSeq sequence libraries across
turbidite boundaries at ~26 cm sediment depth in La Jolla Canyon off the coast of
California, and at ~50 cm depth in meromictic Twin Lake, Hennepin County, MN. 16S
rRNA gene signatures of relict and active bacterial populations exhibit
persistent differences attributable to turbidite deposition. In particular, both
the marine and lacustrine turbidite boundaries are sharply demarcated by the
abundance and diversity of Chloroflexi, suggesting a characteristic sensitivity
to sediment disturbance history or to differences in organic substrates across
turbidite profiles. Variations in the abundance of putative dissimilatory sulfate
reducing Deltaproteobacteria across the buried La Jolla Canyon sediment-water
interface reflect turbidite-induced changes to the geochemical environment.
Species-level distinctions within the Deltaproteobacteria clearly conform to the
sedimentological boundary, suggesting a continuing impact of genetic inheritance
distinguishable from broader trends attributable to selective pressure. Abrupt,
<1-cm scale changes in bacterial diversity across the Twin Lake turbidite contact
are consistent with previous studies showing that relict DNA signatures
attributable to sediment transport may be more easily preserved in low-energy,
anoxic environments. This work raises the possibility that deep subsurface
microbial communities may inherit variations in microbial diversity from sediment
flow and deformation events.
PMID- 29350441
TI - Ultrasensitive detection of Shiga toxin 2 and its variants in Shiga toxin
producing Escherichia coli strains by a time-resolved fluorescence immunoassay.
AB - A rapid and sensitive two-step time-resolved fluorescence immunoassay (TRFIA) was
developed for the detection of Shiga toxin 2 (Stx2) and its variants in Shiga
toxin-producing Escherichia coli (STEC) strains. In sandwich mode, a monoclonal
antibody against Stx2 was coated on a microtiter plate as a capture antibody. A
tracer antibody against Stx2 labeled with europium(III) (Eu3+ ) chelate was then
used as a detector, followed by fluorescence measurements using time-resolved
fluorescence. The sensitivity of Stx2 detection was 0.038 ng/ml (dynamic range,
0.1-1000 ng/ml). The intra- and inter-assay coefficients of variation of the
assay were 3.2% and 3.6%, respectively. The performance of the established assay
was evaluated using culture supernatants of STEC strains, and the results were
compared to those of a common HRP (horseradish peroxidase) labeling immunosorbent
assay. A polymerase chain reaction (PCR) for the detection of genes encoding Stx1
and Stx2 was used as the reference for comparison. Correlation between the Stx2
specific TRFIA and PCR was calculated by the use of kappa statics, exhibiting a
perfect level of agreement. The availability of the sensitive and reliable Stx2
specific TRFIA method for quantifying Stx2 and its variants in STEC strains will
complement bacteria isolation-based platform and aid in the accurate and prompt
diagnosis of STEC infections.
PMID- 29350443
TI - Cutting reduces variation in biomass production of forage crops and allows low
performers to catch up: A case study of Trifolium pratense L. (red clover).
AB - Re-growth of fodder plants after grazing and mowing drives the profitability of
their cultivation and is therefore an important target trait for plant breeding
and agricultural engineering. However, for some fodder plants little is known
about their re-growth dynamics in response to grazing or mowing. We analysed the
native response of plant architecture, leaf morphology and growth performance to
experimental cutting in wild Trifolium pratense L. (red clover) plants. A total
of 150 potted clover plants were established under controlled field conditions,
and half of the plants were cut to 5 cm 3 months after sowing. Each plant was
measured every week for 5 months. The cut and subsequently re-grown plants
carried fewer main branches (-20%), as well as fewer (-13%) and smaller (-32%)
leaves than the control plants. However, the cut plants produced an average of
17% more accumulated leaf area (cut + re-grown leaf area) than the control
plants. This discrepancy was explained by variation in the growth strategy of the
plants, where the cut plants invariably expressed a second growth phase, while
almost half of the untreated plants did not. Our results suggest that cutting
acted as an artificial trigger initiating a second growth phase in the cut plants
and thereby contributed to yield increase. Exploiting this mechanism may set new
goals for breeding and optimisation of the mowing regime.
PMID- 29350442
TI - Role of ethylene and related gene expression in the interaction between
strawberry plants and the plant growth-promoting bacterium Azospirillum
brasilense.
AB - Induced systemic resistance (ISR) is one of the indirect mechanisms of growth
promotion exerted by plant growth-promoting bacteria, and can be mediated by
ethylene (ET). We assessed ET production and the expression of related genes in
the Azospirillum-strawberry plant interaction. Ethylene production was evaluated
by gas chromatography in plants inoculated or not with A. brasilense REC3. Also,
plants were treated with AgNO3 , an inhibitor of ET biosynthesis; with 1
aminocyclopropane-1-carboxylic acid (ACC), a precursor of ET biosynthesis; and
with indole acetic acid (IAA). Plant dry biomass and the growth index were
determined to assess the growth-promoting effect of A. brasilense REC3 in
strawberry plants. Quantitative real time PCR (qRT-PCR) was performed to analyse
relative expression of the genes Faetr1, Faers1 and Faein4, which encode ET
receptors; Factr1 and Faein2, involved in the ET signalling pathway; Faacs1
encoding ACC synthase; Faaco1 encoding ACC oxidase; and Faaux1 and Faami1 for IAA
synthesis enzymes. Results showed that ET acts as a rapid and transient signal in
the first 12 h post-treatment. A. brasilense REC3-inoculated plants had a
significantly higher growth index compared to control plants. Modulation of the
genes Faetr1, Faers1, Faein4, Factr1, Faein2 and Faaco1 indicated activation of
ET synthesis and signalling pathways. The up-regulation of Faaux1 and Faami1
involved in IAA synthesis suggested that inoculation with A. brasilense REC3
induces production of this auxin, modulating ET signalling. Ethylene production
and up-regulation of genes associated with ET signalling in strawberry plants
inoculated with A. brasilense REC3 support the priming activation characteristic
of ISR. This type of resistance and the activation of systemic acquired
resistance previously observed in this interaction indicate that both are present
in strawberry plants, could act synergistically and increase protection against
pathogens.
PMID- 29350444
TI - Four cases of iridociliary tumors in domestic rabbits (Oryctolagus Cuniculus).
AB - Spontaneously occurring ocular neoplasia is rarely reported in rabbits. This case
series presents four cases of rabbits diagnosed with iridociliary tumors, which
have not been previously reported in this species. Major pathological findings
include epithelial tumors affecting the anterior uvea with variable pigmentation
and basement membrane formation. Follow-up information was only available for two
cases, but neither showed evidence of metastasis, suggesting that the prognosis
for these tumors in rabbits, as in other species, may be very good.
PMID- 29350445
TI - Application of computer-aided sperm analysis (CASA) for detecting sperm
immobilizing antibody.
AB - PROBLEM: Since the 1970s, anti-sperm antibodies have been studied as a pathogenic
factor contributing to infertility. The complement-dependent sperm-immobilization
test (SIT) and quantitative SIT have been used as effective tools for detecting
anti-sperm antibodies in clinical settings. These tests have been carried out
traditionally by manually counting the number of motile sperm through eye
estimation. METHOD OF STUDY: In this study, we developed a novel method using
computer-aided sperm analysis. The results were compared with those obtained by
the traditional method. RESULTS: The results were identical and 25 of 78 samples
tested were positive and 53 samples were negative for sperm-immobilizing (SI)
antibodies based on both methods. For SI-positive samples, the values of SI50
obtained using the two methods correlated closely with high co-efficiency.
CONCLUSION: Using the novel method, manually counting the number of motile
spermatozoa becomes unnecessary. The novel method presented here will increase
the objectivity and convenience of using the SIT as a clinical indicator.
PMID- 29350446
TI - Differential gene expression in trigeminal ganglia of male and female rats
following chronic constriction of the infraorbital nerve.
AB - BACKGROUND: The mechanisms underlying sex-based differences in pain and analgesia
are poorly understood. In this study, we investigated gene expression changes in
trigeminal ganglia (TG) of male and female rats exposed to infraorbital nerve
chronic constriction injury (IoN-CCI). METHODS: Somatosensory assessments were
performed prior to IoN-CCI and at selected time points postsurgery. Selected gene
expression changes were examined with real-time quantitative polymerase chain
reaction (RT-PCR) in ipsilateral TG at 21 days postsurgery. RESULTS: Rats exposed
to IoN-CCI developed significant mechanical allodynia and hyperalgesia on days 19
and 21 postsurgery. During this period, females developed significantly more
allodynia but not hyperalgesia compared to males. At 21 days postsurgery,
expression levels of 44 of the 84 investigated pain-related genes in ipsilateral
TG were significantly regulated relative to naive rats in either sex. Csf1 and
Cx3cr1 were up-regulated in both sexes, but the magnitude of regulation was
significantly higher in females (p = 0.02 and p = 0.001, respectively). Htr1a and
Scn9a were down-regulated in both sexes, but the down-regulation was
significantly more pronounced in males (p = 0.04 and p = 0.02, respectively).
Additionally, Cck, Il1a, Pla2g1b and Tnf genes were significantly regulated in
females but not in males, and Chrna4 gene was significantly down-regulated in
males but not in females. CONCLUSIONS: Our findings suggest sex-dependent gene
regulation in response to nerve injury, which may contribute to sex dimorphism of
trigeminal neuropathic pain. Further studies are needed to establish gene
expression changes over time and correlate these with hormonal and other
physiological parameters in male and female. SIGNIFICANCE: We present novel sex
specific transcriptional regulation in trigeminal ganglia that may contribute to
male-/female-based differences in trigeminal neuropathic pain. These findings are
expected to open new research horizons, particularly in male versus female
targeted therapeutic regimens.
PMID- 29350447
TI - Effect of sedation with butorphanol on variables pertaining to the ophthalmic
examination in dogs.
AB - OBJECTIVE: To evaluate whether sedation with intramuscular butorphanol can
interfere with different variables of the ocular examination in dogs. ANIMALS:
Twenty-two beagles without ophthalmic abnormalities. PROCEDURES: Each dog was
examined 20 min prior to and again just before administration of butorphanol to
establish baseline data. The globe and nictitating membrane position was
evaluated, and the following were recorded: menace response, dazzle reflex,
corneal blink reflex, phenol red thread tear test (PRT), Schirmer tear test-1
(STT-1), pupil size (PS) measurement, and rebound tonometry. Then, butorphanol
was injected intramuscularly at a dose of 0.2 mg/kg and these procedures were
repeated 10, 20, 30, and 45 min postadministration. A sedation score graded 0 to
3 was also established at these time points. Statistical analyses were performed
on quantitative data using ANOVA. RESULTS: The sedative effect was not associated
with any changes in globe and nictitating membrane position; did not affect the
results of the menace response, dazzle reflex, and corneal blink reflex; and had
no significant effect on PRT values. However, butorphanol administration was
associated with a statistically significant decrease in STT-1 and PS values (P <
0.005), and a statistically significant increase in IOP (P < 0.05). All these
variations remained in the range of normal values. CONCLUSIONS AND CLINICAL
RELEVANCE: Butorphanol administered intramuscularly at 0.2 mg/kg provided a
degree of sedation allowing eye examination, but was found to interfere with STT
1, PS, and IOP values among the diagnostic tests studied. However, these values
remained within normal limits.
PMID- 29350448
TI - Clinical and genetic associations for carboplatin-related ototoxicity in children
treated for retinoblastoma: A retrospective noncomparative single-institute
experience.
AB - BACKGROUND: Children with retinoblastoma treated with carboplatin chemotherapy
risk moderate to severe, irreversible hearing loss. Based on published evidence,
we hypothesized that ototoxicity risk is associated with clinical parameters and
variants in candidate genes in drug metabolism pathways (methyltransferases
[thiopurine S-methyltransferase, TPMT] and [catechol-O-methyltransferase, COMT],
and drug transporter ABCC3). PROCEDURE: We retrospectively reviewed clinical
records of patients with retinoblastoma treated with carboplatin chemotherapy
regarding age (at diagnosis and chemotherapy initiation), chemotherapy sessions
(cycles number, drug doses, and cumulative carboplatin dose), and hearing loss
(defined as ototoxicity >=grade 2 by at least one classification system). Blood
samples were genotyped for genetic variants in TPMT (rs12201199, rs1800460), COMT
(rs4646316, rs9332377), and ABCC3 (rs1051640) by quantitative PCR and confirmed
by allele-specific PCR. Univariate statistical tests, receiver-operating
characteristic analysis, and Kaplan-Meier curves were used to examine the
association between hearing loss, clinical factors, and variants in candidate
genes. RESULTS: Audiometric data and stored DNA were available for 71 patients
with retinoblastoma (88% carried an RB1 pathogenic variant allele). Median
carboplatin cumulative dose was 1,400 mg/m2 (260-5,148 mg/m2 ). Ototoxicity
occurred in 18 patients (25%), strongly associated with age at diagnosis (P =
0.01) and age at chemotherapy initiation (OR = 4.99, P = 0.008). The highest
likelihood ratio of hearing loss was associated with chemotherapy initiation
<4.25 months of age. Ototoxicity was not associated with any tested genetic
variants. CONCLUSIONS: We observed a 25% prevalence of ototoxicity in patients
with retinoblastoma treated with carboplatin, higher than previously published.
Age at chemotherapy initiation was associated with carboplatin-induced
ototoxicity, with children <4.25 months of age at highest risk.
PMID- 29350449
TI - Lipoidal corneal degeneration in aged falcons.
AB - OBJECTIVE: To present a case series of idiopathic lipoidal corneal degeneration
in falcons. ANIMALS STUDIED: Five falcons including three peregrine falcons
(Falco peregrinus), one prairie falcon (Falco mexicanus), and one red-naped
shaheen (Falco peregrinus babylonicus) were observed to develop slowly
progressive corneal opacification that began at the temporal limbus and extended
centripetally across the cornea over a period of years. Four of the birds were
over 20 years old. PROCEDURES: All animals underwent complete ophthalmic
examinations. A red-naped shaheen underwent ocular imaging via spectral-domain
optical coherence tomography. Two peregrine falcons were euthanized due to
declining health, and their eyes were examined histologically. RESULTS: The
opacities were pale and granular, with frequent vascularization associated
perilimbally. Diffuse neutral lipid was observed in stromal cells throughout the
corneal stroma of both clear and opaque areas of the cornea, sparing only the
acellular anterior limiting lamina. Clusters of cholesterol crystals surrounded
by macrophages were present in the mid-stroma. Fibrosis was evident in a
subepithelial location, which separated the epithelium from the anterior limiting
lamina. Ultrastructurally, diffuse vacuolization of the keratocytes was observed.
No other ophthalmic or systemic abnormalities were noted. CONCLUSIONS: Results
suggest that lipid degeneration occurs rarely in captive falcons of advanced age.
The underlying cause is unclear. Though unsubstantiated, possible contributing
factors include dyslipoproteinemia, corneal trauma, diet, and age-related
alterations in corneal metabolism. The initiation of pathology at the temporal
limbus, as well as slow progression, suggests that exposure contributes to the
onset and progression of this unique keratopathy.
PMID- 29350450
TI - Cross-sectional and longitudinal analysis of nutritional status of school
children from Bumbire Island (United Republic of Tanzania).
AB - OBJECTIVE: To analyze the nutritional status of schoolchildren from Bumbire
Island (Tanzania) from cross-sectional and longitudinal perspectives. METHODS:
During 2014 and 2015, we collected anthropometric measurements in a sample of 437
schoolchildren (226 males, 211 females; 5-16 years). A sub-sample of 126 children
were measured in both surveys. Socio-demographic data have been taken and dietary
habits investigated. The accuracy of age data was checked. Malnutrition
prevalence was calculated according to the WHO references and the z-score
criteria. RESULTS: The prevalence of undernutrition was high (stunting: 30.7%;
underweight: 12.9%; thinness: 4.5%), while overweight was rare (2.4%). The
prevalence of stunting was higher in males and in older children. The one-year
longitudinal analysis indicated that stunting prevalence increased. CONCLUSIONS:
Undernutrition is affecting Bumbire Island children, likely due to micronutrient
deficiencies. The effects of linear growth deficit continue to accumulate
throughout childhood and adolescent years.
PMID- 29350451
TI - Morphological specializations of the epidermis of an angler catfish Chaca chaca
(Siluriformes, Chacidae) in relation to its ecological niche: A scanning electron
microscopic investigation.
AB - The present work was undertaken with the aim to deduce morphological adaptations
in skin of an angler catfish Chaca chaca by means of scanning electron
microscopy. The fish is nocturnal, bottom dwelling, sluggish, ambush predator,
lives in sand, mud, or soft substrates often buried and camouflaged for
protection and to feed. The surface of the epidermis is covered with polygonal
epithelial cells, each having surface relief of microridges forming intricate
patterns. In between epithelial cells irregularly distributed mucous cell
openings, randomly distributed epidermal specialized structures, taste buds, and
neuromasts are discernible. The epidermal specialized structures are keratinized.
These are either irregularly the rounded elevated plaque like or the cone shaped
structures. The superficial keratinized cells could frequently be discernible
exfoliated at the surface. At intervals, characteristic epidermal projections
could be observed. Surface of these projections at intervals is differentiated
into short stumpy protuberances, each bearing a taste bud at its summit. Further,
near the basal portion of these epidermal projections, conical, or rounded plaque
like epidermal specialized structures are also discernible. The surface sculpture
of the skin of Chaca chaca is associated with the structural and functional
significance and physiological adaptations of the epidermis with respect to its
ecological niche.
PMID- 29350452
TI - Anatomical and phenological implications of the relationship between Schinus
polygama (Cav.) (Cabrera) and the galling insect Calophya rubra (Blanchard).
AB - The success of galling insects could be determined by synchronisation with host
plant phenology and climate conditions, ensuring suitable oviposition sites for
gall induction and food resources for their survival. The anatomical,
histochemical and phenological synchronisation strategies between Calophya rubra
(Blanchard) (Hemiptera: Psylloidea) and its host, the evergreen plant Schinus
polygama (Cav.) (Cabrera) (Anacardiaceae), in the Mediterranean climate of
southern Chile was evaluated and compared to that of the congeneric C. cf.
duvauae (Scott) from Brazil and closely related host plant S. engleri in a
subtropical climate. Anatomical, histometric, histochemical and vegetative
phenology studies of the stem and galls were conducted from June 2015 to December
2016. Based on the anatomical, histometric and histochemical analysis, the
conical stem gall traits imply gains over the non-galled stem toward the galling
insect survival, but the maintenance of phellem, secretory ducts and pith
indicate conservative developmental traits that cannot be manipulated by C.
rubra. Our results indicate that the conditions of the Mediterranean climate zone
limit C. rubra immature activity during unfavourable periods, probably
determining a diapause period and a univoltine life cycle, which are
peculiarities of the S. polygama- C. rubra system. The synchronisation between
development and seasonality confers peculiarities to the S. polygama- C. rubra
system in the Mediterranean climate zone.
PMID- 29350453
TI - Late Cretaceous marine arthropods relied on terrestrial organic matter as a food
source: Geochemical evidence from the Coon Creek Lagerstatte in the Mississippi
Embayment.
AB - The Upper Cretaceous Coon Creek Lagerstatte of Tennessee, USA, is known for its
extremely well-preserved mollusks and decapod crustaceans. However, the
depositional environment of this unit, particularly its distance to the
shoreline, has long been equivocal. To better constrain the coastal proximity of
the Coon Creek Formation, we carried out a multiproxy geochemical analysis of
fossil decapod (crab, mud shrimp) cuticle and associated sediment from the type
section. Elemental analysis and Raman spectroscopy confirmed the presence of
kerogenized carbon in the crabs and mud shrimp; carbon isotope (delta13 C)
analysis of bulk decapod cuticle yielded similar mean delta13 C values for both
taxa (-25.10/00 and -260/00, respectively). Sedimentary biomarkers were composed
of n-alkanes from C16 to C36 , with the short-chain n-alkanes dominating, as well
as other biomarkers (pristane, phytane, hopanes). Raman spectra and biomarker
thermal maturity indices suggest that the Coon Creek Formation sediments are
immature, which supports retention of unaltered, biogenic isotopic signals in the
fossil organic carbon remains. Using our isotopic results and published calcium
carbonate delta13 C values, we modeled carbon isotope values of carbon sources in
the Coon Creek Formation, including potential marine (phytoplankton) and
terrestrial (plant) dietary sources. Coon Creek Formation decapod delta13 C
values fall closer to those estimated for terrigenous plants than marine
phytoplankton, indicating that these organisms were feeding primarily on
terrigenous organic matter. From this model, we infer that the Coon Creek
Formation experienced significant terrigenous organic matter input via a
freshwater source and thus was deposited in a shallow, nearshore marine
environment proximal to the shoreline. This study helps refine the paleoecology
of nearshore settings in the Mississippi Embayment during the global climatic
shift in the late Campanian-early Maastrichtian and demonstrates for the first
time that organic delta13 C signatures in exceptionally preserved fossil marine
arthropods are a viable proxy for use in paleoenvironmental reconstructions.
PMID- 29350454
TI - Patterns of Internet-based health information seeking in adult survivors of
childhood cancer.
AB - BACKGROUND: To assess where, when, and why survivors of childhood cancer seek
health information. PROCEDURE: Data from the Childhood Cancer Survivor Study
(CCSS) cohort (n = 1386) and Health Information National Trends Survey (n = 2385)
were analyzed to determine the health information seeking strategies of childhood
cancer survivors. Descriptive frequencies, chi2 analyses, t-tests, and
multivariable logistic regression models were used. RESULTS: To seek health
related information for themselves, 54% (n = 742) of the childhood survivors
reported using the Internet in the past 12 months, compared to 45% of the general
population (adjusted OR: 2.76; 95% CI: 2.40-3.19). Childhood cancer survivors who
used the Internet for health information were more likely to be female, between
the ages of 18-34, have received some college education or be a college graduate,
and report being in poor health. Although survivors were less likely than the
general population to trust health information from the Internet (P < 0.01), they
indicated that they would like a secure website that uses information from their
medical records to provide individualized health-related information. CONCLUSION:
The use of the Internet to access health information among the childhood cancer
survivors was over 50%. Information on late effects was a high priority for most
survivors, as was their interest in websites related to late effects and a
website on patient information tailored to personal situations. Identification of
factors associated with searching the Internet for cancer information may provide
direction for development of effective cancer communication interventions for
this at-risk population.
PMID- 29350455
TI - A novel prognostic six-CpG signature in glioblastomas.
AB - AIMS: We aimed to identify a clinically useful biomarker using DNA methylation
based information to optimize individual treatment of patients with glioblastoma
(GBM). METHODS: A six-CpG panel was identified by incorporating genome-wide DNA
methylation data and clinical information of three distinct discovery sets and
was combined using a risk-score model. Different validation sets of GBMs and
lower-grade gliomas and different statistical methods were implemented for
prognostic evaluation. An integrative analysis of multidimensional TCGA data was
performed to molecularly characterize different risk tumors. RESULTS: The six-CpG
risk-score signature robustly predicted overall survival (OS) in all discovery
and validation cohorts and in a treatment-independent manner. It also predicted
progression-free survival (PFS) in available patients. The multimarker epigenetic
signature was demonstrated as an independent prognosticator and had better
performance than known molecular indicators such as glioma-CpG island methylator
phenotype (G-CIMP) and proneural subtype. The defined risk subgroups were
molecularly distinct; high-risk tumors were biologically more aggressive with
concordant activation of proangiogenic signaling at multimolecular levels.
Accordingly, we observed better OS benefits of bevacizumab-contained therapy to
high-risk patients in independent sets, supporting its implication in guiding
usage of antiangiogenic therapy. Finally, the six-CpG signature refined the risk
classification based on G-CIMP and MGMT methylation status. CONCLUSIONS: The
novel six-CpG signature is a robust and independent prognostic indicator for GBMs
and is of promising value to improve personalized management.
PMID- 29350456
TI - A prospective study of family predictors of health-related quality of life in
pediatric brain tumor survivors.
AB - BACKGROUND: The objective of this study was to examine prospectively the
associations between family functioning at the end of tumor-directed treatment
and the health-related quality of life (HRQL) of pediatric brain tumor survivors
(PBTSs) approximately 9 months later. PROCEDURE: Thirty-five PBTS (age 6-16
years) and their mothers completed measures of family functioning and survivor
HRQL within 5 months of completing tumor-directed therapy (baseline) and again
approximately 9 months later (follow-up). RESULTS: Survivor-rated general family
functioning at baseline significantly predicted mother proxy- and self-reported
survivor HRQL at follow-up when controlling for survivor HRQL at baseline and
relevant demographic and treatment-related variables. CONCLUSIONS: Family
functioning is a key factor contributing to survivor HRQL and should be screened
throughout the course of tumor-directed treatment. Psychosocial interventions
directed toward improving general family functioning may improve survivor well
being following the completion of treatment.
PMID- 29350457
TI - Improved outcome at end of treatment in the collaborative Wilms tumour Africa
project.
AB - BACKGROUND: The Collaborative Wilms Tumour (WT) Africa Project has implemented an
adapted WT treatment guideline in sub-Saharan Africa as a multi-centre
prospective clinical trial. A retrospective, baseline evaluation of end-of
treatment outcome was performed for a 2-year period prior to the introduction of
this guideline. The collaborative project aims to reduce both treatment
abandonment and death during treatment to less than 10% for improving survival.
PROCEDURE: All participating centres obtained local Institutional Research Board
(IRB) approval and implemented the adapted WT treatment guideline. End-of
treatment outcome was documented for 2 years. It was divided into alive without
evidence of disease, treatment abandonment, death during treatment and persistent
disease. The outcome of children enroled in the first 2 years of the prospective
clinical trial has been compared to the outcome before the start of the project.
RESULTS: One hundred twenty-two patients were included in the baseline evaluation
(2011-2012) and 133 in the first 2 years of the collaborative clinical trial
(2014-2015). The percentage of patients alive without evidence of disease at the
end of treatment increased from 52% (63/122) to 68% (90/133; P = 0.01). Treatment
abandonment decreased from 23% (28/122) to 13% (17/133; P = 0.03). Death during
treatment decreased from 21% (26/122) to 13% (17/133; P = 0.07). CONCLUSION: This
collaboration, using relatively simple and low-cost interventions, led to a
significant decrease in treatment abandonment and increase in survival without
evidence of disease at the end of treatment.
PMID- 29350458
TI - Der-Cherng Liang, MD, 1947-2017.
PMID- 29350459
TI - NOURISH-T: Targeting caregivers to improve health behaviors in pediatric cancer
survivors with obesity.
AB - BACKGROUND: Obesity rates in pediatric cancer survivors (PCS) are alarmingly
high. Although healthy lifestyle changes may prevent future health complications,
promoting healthy behaviors in PCS is challenging, and few interventions have
successfully addressed this issue. PROCEDURE: This randomized control trial
evaluated the feasibility and preliminary effectiveness of a parent-focused six
session intervention, NOURISH-T (Nourishing Our Understanding of Role Modeling to
Improve Support and Health for Healthy Transitions), compared with enhanced usual
care (EUC) on the outcomes of caregiver and PCS anthropometric measurements,
eating behaviors, and physical activity. Behavioral and self-report assessments
of caregivers and PCS in both conditions were conducted at baseline,
postintervention, and at a 4-month follow-up. RESULTS: In comparison to no change
among EUC caregivers, NOURISH-T caregivers showed small yet significant decreases
from baseline through follow-up on BMI, waist-hip ratio, and total daily caloric
intake. However, there was no change with regard to daily fat and sugar intake.
NOURISH-T caregivers also showed positive changes in their child feeding
behaviors, including decreases in pressuring their child to eat and restricting
their child's eating and increased eating together as a family. Similarly,
decreases in BMI percentile, waist-hip ratio, and sugary beverage consumption
were found for NOURISH-T PCS from baseline to postintervention. NOURISH-T PCS
also significantly increased their daily steps, whereas EUC PCS decreased their
daily steps. CONCLUSIONS: Results suggest that an intervention targeting parents
is feasible and demonstrates preliminary effectiveness. NOURISH-T showed a longer
term effect on caregivers, and, although shorter term effect, a positive impact
on the PCS themselves. Implications for ways to improve NOURISH-T as an
intervention for increasing healthy behaviors of PCS are discussed.
PMID- 29350460
TI - Three-generation family with novel contiguous gene deletion on chromosome 2p22
associated with thoracic aortic aneurysm syndrome.
AB - Latent transforming growth factor binding proteins (LTBP) are a family of
extracellular matrix glycoproteins that play an important role in the regulation
of transforming growth factor beta (TGF-beta) activation. Dysregulation of the
TGF-beta pathway has been implicated in the pathogenesis of inherited disorders
predisposing to thoracic aortic aneurysms syndromes (TAAS) including Marfan
syndrome (MFS; FBN1) and Loeys-Dietz syndrome (LDS; TGFBR1, TGFBR2, TGFB2, TGFB3,
SMAD2, SMAD3). While these syndromes have distinct clinical criteria, they share
clinical features including aortic root dilation and musculoskeletal findings.
LTBP1 is a component of the TGF-beta pathway that binds to fibrillin-1 in the
extracellular matrix rendering TGF-beta inactive. We describe a three-generation
family case series with a heterozygous ~5.1 Mb novel contiguous gene deletion of
chromosome 2p22.3-p22.2 involving 11 genes, including LTBP1. The deletion has
been identified in the proband, father and grandfather, who all have a phenotype
consistent with a TAAS. Findings include thoracic aortic dilation, ptosis, malar
hypoplasia, high arched palate, retrognathia, pes planus, hindfoot deformity,
obstructive sleep apnea, and low truncal tone during childhood with joint laxity
that progressed to reduced joint mobility over time. While the three affected
individuals did not meet criteria for either MFS or LDS, they shared features of
both. Although the deletion includes 11 genes, given the relationship between
LTBP1, TGF-beta, and fibrillin-1, LTBP1 stands out as one of the possible
candidate genes for the clinical syndrome observed in this family. More studies
are necessary to evaluate the potential role of LTBP1 in the pathophysiology of
TAAS.
PMID- 29350461
TI - Is testicular irradiation necessary for patients with acute lymphoblastic
leukemia and testicular relapse?
PMID- 29350462
TI - Mesoaortic compression of a left-sided inferior vena-cava presenting as recurrent
pulmonary embolism in a child-a novel anatomic thrombophilia?
PMID- 29350463
TI - BRIM-P: A phase I, open-label, multicenter, dose-escalation study of vemurafenib
in pediatric patients with surgically incurable, BRAF mutation-positive melanoma.
AB - BACKGROUND: Vemurafenib, a selective inhibitor of BRAF kinase, is approved for
the treatment of adult stage IIIc/IV BRAF V600 mutation-positive melanoma. We
conducted a phase I, open-label, dose-escalation study in pediatric patients aged
12-17 years with this tumor type (NCT01519323). PROCEDURE: Patients received
vemurafenib orally until disease progression. Dose escalation was conducted using
a 3 + 3 design. Patients were monitored for dose-limiting toxicities (DLTs)
during the first 28 days of treatment to determine the maximum tolerated dose
(MTD). Safety/tolerability, tumor response, and pharmacokinetics were evaluated.
RESULTS: Six patients were enrolled (720 mg twice daily [BID], n = 3; 960 mg BID
[n = 3]). The study was terminated prematurely due to low enrollment. No DLTs
were observed; thus, the MTD could not be determined. All patients experienced at
least one adverse event (AE); the most common were diarrhea, headache,
photosensitivity, rash, nausea, and fatigue. Three patients experienced serious
AEs, one patient developed secondary cutaneous malignancies, and five patients
died following disease progression. Mean steady-state plasma concentrations of
vemurafenib following 720 mg and 960 mg BID dosing were similar or higher,
respectively, than in adults. There were no objective responses. Median
progression-free survival and overall survival were 4.4 months (95% confidence
interval [CI] = 2.7-5.2) and 8.1 months (95% CI = 5.1-12.0), respectively.
CONCLUSIONS: A recommended and effective dose of vemurafenib for patients aged 12
17 years with metastatic or unresectable melanoma was not identified. Extremely
low enrollment in this trial highlights the importance of considering the
inclusion of adolescents with adult cancers in adult trials.
PMID- 29350464
TI - Predictors of response, progression-free survival, and overall survival using
NANT Response Criteria (v1.0) in relapsed and refractory high-risk neuroblastoma.
AB - PURPOSE: The New Approaches to Neuroblastoma Therapy Response Criteria (NANTRC)
were developed to optimize response assessment in patients with
recurrent/refractory neuroblastoma. Response predictors and associations of the
NANTRC version 1.0 (NANTRCv1.0) and prognostic factors with outcome were
analyzed. METHODS: A retrospective analysis was performed of patients with
recurrent/refractory neuroblastoma enrolled from 2000 to 2009 on 13 NANT Phase
1/2 trials. NANTRC overall response integrated CT/MRI (Response Evaluation
Criteria in Solid Tumors [RECIST]), metaiodobenzylguanidine (MIBG; Curie
scoring), and percent bone marrow (BM) tumor (morphology). RESULTS: Fourteen
(6.9%) complete response (CR) and 14 (6.9%) partial response (PR) occurred among
203 patients evaluable for response. Five-year progression-free survival (PFS)
was 16 +/- 3%; overall survival (OS) was 27 +/- 3%. Disease sites at enrollment
included MIBG-avid lesions (100% MIBG trials; 84% non-MIBG trials), measurable
CT/MRI lesions (48%), and BM (49%). By multivariable analysis, Curie score of 0
(P < 0.001), lower Curie score (P = 0.003), no measurable CT/MRI lesions (P =
0.044), and treatment on peripheral blood stem cell (PBSC) supported trials (P =
0.005) were associated with achieving CR/PR. Overall response of stable disease
(SD) or better was associated with better OS (P < 0.001). In multivariable
analysis, MYCN amplification (P = 0.037) was associated with worse PFS;
measurable CT/MRI lesions (P = 0.041) were associated with worse OS; prior
progressive disease (PD; P < 0.001/P < 0.001), Curie score >= 1 (P < 0.001; P =
0.001), higher Curie score (P = 0.048/0.037), and treatment on non-PBSC trials (P
= < 0.001/0.003) were associated with worse PFS and OS. CONCLUSIONS: NANTRCv1.0
response of at least SD is associated with better OS in patients with
recurrent/refractory neuroblastoma. Patient and tumor characteristics may predict
response and outcome. Identifying these variables can optimize Phase 1/2 trial
design to select novel agents for further testing.
PMID- 29350465
TI - Proteomics Analysis of Skeletal Muscle from Leptin-Deficient ob/ob Mice Reveals
Adaptive Remodeling of Metabolic Characteristics and Fiber Type Composition.
AB - Skeletal muscle insulin resistance, an early metabolic defect in the pathogenesis
of type 2 diabetes (T2D), may be a cause or consequence of altered protein
expression profiles. Proteomics technology offers enormous promise to investigate
molecular mechanisms underlying pathologies, however, the analysis of skeletal
muscle is challenging. Using state-of-the-art multienzyme digestion and filter
aided sample preparation (MED-FASP) and a mass spectrometry (MS)-based workflow,
we performed a global proteomics analysis of skeletal muscle from leptin
deficient, obese, insulin resistant (ob/ob) and lean mice in mere two fractions
in a short time (8 h per sample). We identified more than 6000 proteins with 118
proteins differentially regulated in obesity. This included protein kinases,
phosphatases, and secreted and fiber type associated proteins. Enzymes involved
in lipid metabolism in skeletal muscle from ob/ob mice were increased, providing
evidence against reduced fatty acid oxidation in lipid-induced insulin
resistance. Mitochondrial and peroxisomal proteins, as well as components of
pyruvate and lactate metabolism, were increased. Finally, the skeletal muscle
proteome from ob/ob mice displayed a shift toward the "slow fiber type." This
detailed characterization of an obese rodent model of T2D demonstrates an
efficient workflow for skeletal muscle proteomics, which may easily be adapted to
other complex tissues.
PMID- 29350466
TI - Simultaneous extraction and determination of trace amounts of diclofenac from
whole blood using supported liquid membrane microextraction and fast Fourier
transform voltammetry.
AB - A novel, simple, and inexpensive analytical technique based on flat sheet
supported liquid membrane microextraction coupled with fast Fourier transform
stripping cyclic voltammetry on a reduced graphene oxide carbon paste electrode
was used for the extraction and online determination of diclofenac in whole
blood. First, diclofenac was extracted from blood samples using a
polytetrafluoroethylene membrane impregnated with 1-octanol and then into an
acceptor solution, subsequently it was oxidized on a carbon paste electrode
modified with reduced graphene oxide nanosheets. The optimal values of the key
parameters influencing the method were as follows: scan rate, 6 V/s; stripping
potential, 200 mV; stripping time, 5 s; pH of the sample solution, 5; pH of the
acceptor solution,7; and extraction time, 240 min. The calibration curves were
plotted for the whole blood samples and the method was found to have a good
linearity within the range of 1-25 MUg/mL with a determination coefficient of
0.99. The limits of detection and quantification were 0.1 and 1.0 MUg/mL,
respectively. Using this coupled method, the extraction and determination were
merged into one step. Accordingly, the speed of detection for sensitive
determination of diclofenac in complex samples, such as blood, increased
considerably.
PMID- 29350467
TI - Alveolar soft part sarcoma in children and young adults: A report of 69 cases.
AB - BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare mesenchymal tumor
characterized by ASPL-TFE3 translocation. Apart from complete surgical resection,
there is no standard management strategy. PROCEDURE: The clinical data of 69
children and young adults less than 30 years old with ASPS diagnosed from 1980
2014 were retrospectively collected from four major institutions. RESULTS: Median
age at diagnosis was 17 years (range: 1.5-30). Forty-four (64%) were female.
Median follow-up was 46 months (range: 1-409). Most common primary sites were
limbs (58%) and trunk (24%). ASPL-TFE3 translocation was present in all 26
patients tested. IRS postsurgical staging was I in 19 (28%), II in 7 (10%), III
in 5 (7%), and IV in 38 (55%) patients. The 5-year event-free survival (EFS) and
overall survival (OS) were 38% and 72%, respectively. The 5-year EFS and OS were
80% and 87%, respectively, for the 31 patients with localized tumors (IRS-I-II
III), and 7% and 61%, respectively, for the 38 patients with metastatic tumors
(IRS-IV). Of 11 IRS-IV patients who received targeted therapy upfront, two had
partial response, six had stable disease, and three had progressive disease.
Median time to progression for IRS-IV patients was 12 months for those treated
with targeted therapy, 7 months for cytotoxic chemotherapy (N = 15), and 4 months
for observation only (N = 6). CONCLUSION: Localized ASPS has a good prognosis
after gross total resection. ASPS is resistant to cytotoxic chemotherapy.
Although there are no curative therapies for patients with metastatic disease,
prolonged disease stabilization may be achieved with targeted therapies.
PMID- 29350469
TI - In vitro to in vivo benchmark dose comparisons to inform risk assessment of
quantum dot nanomaterials.
AB - Engineered nanomaterials are currently under review for their potential toxicity;
however, their use in consumer/commercial products has continued to outpace risk
assessments. In vitro methods may be utilized as tools to improve the efficiency
of risk assessment approaches. We propose a framework to compare relationships
between previously published in vitro and in vivo toxicity assessments of cadmium
selenium containing quantum dots (QDs) using benchmark dose (BMD) and dosimetric
assessment methods. Although data were limited this approach was useful for
identifying sensitive assays and strains. In vitro studies assessed effects of
QDs in three pulmonary cell types across two mouse strains. Significant dose
response effects were modeled and a standardized method of BMD analysis was
performed as a function of both exposure dose and dosimetric dose. In vivo
studies assessed pulmonary effects of QD exposure across eight mouse strains. BMD
analysis served as a basis for relative comparison with in vitro studies. We
found consistent responses in common endpoints between in vitro and in vivo
studies. Strain sensitivity was consistent between in vitro and in vivo studies,
showing A/J mice more sensitive to QDs. Cell types were found to differentially
take up QDs. Dosimetric adjustments identified similar sensitivity among cell
types. Thus, BMD analysis can be used as an effective tool to compare the
sensitivity of different strains, cell types, and assays to QDs. These methods
allow for in vitro assays to be used to predict in vivo responses, improve the
efficiency of in vivo studies, and allow for prioritization of nanomaterial
assessments. This article is categorized under: Toxicology and Regulatory Issues
in Nanomedicine > Toxicology of Nanomaterials Toxicology and Regulatory Issues in
Nanomedicine > Regulatory and Policy Issues in Nanomedicine.
PMID- 29350470
TI - Specific expression of PD-L1 in RELA-fusion supratentorial ependymoma:
Implications for PD-1-targeted therapy.
AB - BACKGROUND: A desperate need for novel therapies in pediatric ependymoma (EPN)
exists, as chemotherapy remains ineffective and radiotherapy often fails. EPN
have significant infiltration of immune cells, which correlates with outcome.
Immune checkpoint inhibitors provide an avenue for new treatments. This study
characterizes tumor-infiltrating immune cells in EPN and aims at predicting
candidates for clinical trials using checkpoint inhibitors targeting PD-L1/PD-1
(programmed death ligand 1/programmed death 1). METHODS: The transcriptomic
profiles of the primary study cohort of EPN and other pediatric brain tumors were
interrogated to identify PD-L1 expression levels. Transcriptomic findings were
validated using the western blotting, immunohistochemistry and flow cytometry.
RESULTS: We evaluated PD-L1 mRNA expression across four intracranial subtypes of
EPN in two independent cohorts and found supratentorial RELA fusion (ST-RELA)
tumors to have significantly higher levels. There was a correlation between high
gene expression and protein PD-L1 levels in ST-RELA tumors by both the western
blot and immunohistochemisty. The investigation of EPN cell populations revealed
PD-L1 was expressed on both tumor and myeloid cells in ST-RELA. Other subtypes
had little PD-L1 in either tumor or myeloid cell compartments. Lastly, we
measured PD-1 levels on tumor-infiltrating T cells and found ST-RELA tumors
express PD-1 in both CD4 and CD8 T cells. A functional T-cell exhaustion assay
found ST-RELA T cells to be exhausted and unable to secrete IFNgamma on
stimulation. CONCLUSIONS: These findings in ST-RELA suggest tumor evasion and
immunsuppression due to PD-L1/PD-1-mediated T-cell exhaustion. Trials of
checkpoint inhibitors in EPN should be enriched for ST-RELA tumors.
PMID- 29350471
TI - Variability Assessment of 90 Salivary Proteins in Intraday and Interday Samples
from Healthy Donors by Multiple Reaction Monitoring-Mass Spectrometry.
AB - PURPOSE: Saliva is an attractive sample source for the biomarker-based testing of
several diseases, especially oral cancer. Here, we sought to apply multiplexed LC
MRM-MS to precisely quantify 90 disease-related proteins and assess their intra-
and interindividual variability in saliva samples from healthy donors.
EXPERIMENTAL DESIGN: We developed two multiplexed LC-MRM-MS assays for 122
surrogate peptides representing a set of disease-related proteins. Saliva samples
were collected from 10 healthy volunteers at three different time points (Day 1
morning and afternoon, and Day 2 morning). Each sample was spiked with a constant
amount of a 15 N-labeled protein and analyzed by MRM-MS in triplicate.
Quantitative results from LC-MRM-MS were calculated by single-point
quantification with reference to a known amount of internal standard (heavy
peptide). RESULTS: The CVs for assay reproducibility and technical variation were
13 and 11%, respectively. The average concentrations of the 99 successfully
quantified proteins ranged from 0.28 +/- 0.58 ng mL-1 for profilin-2 (PFN2) to
8.55 +/-8.96 MUg mL-1 for calprotectin (S100A8). For the 90 proteins detectable
in >50% of samples, the average CVs for intraday, interday, intraindividual, and
interindividual samples were 38%, 43%, 45%, and 69%, respectively. The
fluctuations of most target proteins in individual subjects were found to be
within +/- twofold. CONCLUSIONS AND CLINICAL RELEVANCE: Our study elucidated the
intra- and interindividual variability of 90 disease-related proteins in saliva
samples from healthy donors. The findings may facilitate the further development
of salivary biomarkers for oral and systemic diseases.
PMID- 29350473
TI - 2018: An update on JOPM progress over the last year.
PMID- 29350472
TI - The chemistry and pharmacology of synthetic cannabinoid SDB-006 and its
regioisomeric fluorinated and methoxylated analogs.
AB - Synthetic cannabinoids are the largest and most structurally diverse class of new
psychoactive substances, with manufacturers often using isomerism to evade
detection and circumvent legal restriction. The regioisomeric methoxy- and
fluorine-substituted analogs of SDB-006 (N-benzyl-1-pentyl-1H-indole-3
carboxamide) were synthesized and could not be differentiated by gas
chromatography-mass spectrometry (GC-MS), but were distinguishable by liquid
chromatography-quadrupole time-of-flight-MS (LC-QTOF-MS). In a fluorescence-based
plate reader membrane potential assay, SDB-006 acted as a potent agonist at human
cannabinoid receptors (CB1 EC50 = 19 nM). All methoxy- and fluorine-substituted
analogs showed reduced potency compared to SDB-006, although the 2-fluorinated
analog (EC50 = 166 nM) was comparable to known synthetic cannabinoid RCS-4 (EC50
= 146 nM). Using biotelemetry in rats, SDB-006 and RCS-4 evoked comparable
reduction in body temperature (~0.7 degrees C at a dose of 10 mg/kg), suggesting
lower potency than the recent synthetic cannabinoid AB-CHMINACA (>2 degrees C, 3
mg/kg).
PMID- 29350474
TI - Happy Times for the Macromolecular Journals.
PMID- 29350475
TI - Water deficit disrupts male gametophyte development in Quercus ilex.
AB - Tree species distribution, and hence forest biodiversity, relies on the
reproductive capacity of trees, which is currently affected by climate change.
Drought-induced pollen sterility could increase as a consequence of more intense
and more frequent droughts projected for temperate and Mediterranean regions, and
threaten the sexual regeneration of trees in these regions. To evaluate this
possibility, we examined the effect of long-term partial rainfall exclusion (-27%
precipitation) on male reproductive development in holm oak, Quercus ilex, one of
the most important and widespread tree species of the Mediterranean region. We
examined anther area, pollen production, pollen abortion as well as viable pollen
production in control and dry treatments. Microscopic examinations revealed
significant differences in pollen development between trees in the dry and the
control treatments, even though anthesis occurred before the onset of annual
drought. Our results demonstrate that anthers collected from Q. ilex trees in the
dry treatment, which experienced long-term increased drought stress especially
during the summer, were the same size as anthers in the control treatment, but
displayed 25% pollen abortion and almost 20% reduction in pollen production.
Subsequently, the number of viable pollen grains in anthers from dry treatment
was 35% less than in control. These results suggest a carry-over effect of
drought stress on pollen production that could reduce the reproductive success of
Q. ilex. The results have broad implications for better understanding of the
determinants of tree reproduction by masting and anticipate the outcomes of
expected drought increase in the Mediterranean on forest dynamics.
PMID- 29350477
TI - Pharmacokinetic evaluation and safety of topical 1% morphine sulfate application
on the healthy equine eye.
AB - OBJECTIVE: To determine if corneal epithelial cell integrity is detrimentally
affected by short-term administration of 1.0% morphine sulfate. Additionally, we
sought to determine if topical 1.0% morphine applied to the equine cornea would
result in ocular or systemic absorption. ANIMAL STUDIED: Six healthy horses.
PROCEDURE: Morphine sulfate (1.0%) was applied topically to one eye every four
hours for 72 h before horses were euthanized. Serum samples were collected at
varying time points during the study and aqueous and vitreous humor were
collected immediately after euthanasia. Morphine quantification in serum,
aqueous, and vitreous humor was performed by ELISA. Treated and control corneas
were submitted for histopathology. Horses were monitored for adverse ocular and
systemic effects throughout the study period. RESULTS: All horses developed mild
mucoid ocular discharge in the treated eye. One horse developed a fever during
treatment. Morphine was detected in the aqueous humor of the treated eye for all
horses with mean +/- standard deviation of 165.18 ng/mL +/- 87.69 ng/mL. Morphine
was detected in vitreous humor of the treated eye of 5 of 6 horses with mean +/-
standard deviation of 4.87 +/- 4.46 ng/mL. Morphine was detected in the serum of
5 of 6 horses at varying time points. Maximum systemic concentration reached in a
single horse was 6.98 ng/mL. Corneal histopathology revealed no difference in
microscopic appearance between morphine-treated and control corneas. CONCLUSIONS:
Topical administration of 1.0% morphine sulfate did not appear to cause any
significant ocular or systemic adverse effects. Topical ophthalmic morphine
application resulted in both ocular and systemic absorption.
PMID- 29350476
TI - Investigating the mechanisms underlying phytoprotection by plant growth-promoting
rhizobacteria in Spartina densiflora under metal stress.
AB - Pollution of coasts by toxic metals and metalloids is a worldwide problem for
which phytoremediation using halophytes and associated microbiomes is becoming
relevant. Metal(loid) excess is a constraint for plant establishment and
development, and plant growth promoting rhizobacteria (PGPR) mitigate plant
stress under these conditions. However, mechanisms underlying this effect remain
elusive. The effect of toxic metal(loid)s on activity and gene expression of ROS
scavenging enzymes in roots of the halophyte Spartina densiflora grown on real
polluted sediments in a greenhouse experiment was investigated. Sediments of the
metal-polluted joint estuary of Tinto and Odiel rivers and control, unpollutred
samples from the Piedras estuary were collected and submitted to ICP-OES. Seeds
of S. densiflora were collected from the polluted Odiel marshes and grown in
polluted and unpolluted sediments. Rhizophere biofilm-forming bacteria were
selected based on metal tolerance and inoculated to S. densiflora and grown for 4
months. Fresh or frozen harvested plants were used for enzyme assays and gene
expression studies, respectively. Metal excess induced SOD (five-fold increase),
whereas CAT and ascorbate peroxidase displayed minor induction (twofold). A
twofold increase of TBARs indicated membrane damage. Our results showed that
metal-resistant PGPR (P. agglomerans RSO6 and RSO7 and B. aryabhattai RSO25)
contributed to alleviate metal stress, as deduced from lower levels of all
antioxidant enzymes to levels below those of non-exposed plants. The oxidative
stress index (OSI) decreased between 50 and 75% upon inoculation. The results
also evidenced the important role of PAL, involved in secondary metabolism and/or
lignin synthesis, as a pathway for metal stress management in this halophyte upon
inoculation with appropriate PGPR, since the different inoculation treatments
enhanced PAL expression between 3.75- and five-fold. Our data confirm, at the
molecular level, the role of PGPR in alleviating metal stress in S. densiflora
and evidence the difficulty of working with halophytes for which little genetic
information is available.
PMID- 29350478
TI - Enzymatic scarification of Anacamptis morio (Orchidaceae) seed facilitates lignin
degradation, water uptake and germination.
AB - The seed coat of many species contains hydrophobic lignins, and in soil the
action of microbial ligninases may contribute to release from dormancy.
Laboratory use of ligninases to stimulate germination is promising because of the
specific action on the seed coat, whereas chemical scarification agents may also
corrode the embryo. We hypothesised that exposure of Anacamptis morio
(Orchidaceae) seeds to fungal laccase would stimulate germination, and that the
mechanism involves lignin degradation and increased imbibition. Germination
capacity in vitro was quantified with 1 U filter-sterilised laccase added to agar
medium following autoclaving, compared to a 10% bleach solution (standard bleach
surface sterilisation/scarification method used in orchid seed sowing). Lignin
degradation was quantified using an optical method (phloroglucinol-HCl staining)
combined with image analysis, following experimental pre-treatments involving
immersion in laccase solution, distilled water (negative control) or bleach
(positive control). Water uptake after experimental treatments was quantified as
the proportion of seeds exhibiting visible uptake of an aqueous fluorochrome
under UV excitation. Laccase stimulated a doubling of germination in vitro with
respect to bleach surface sterilisation/scarification alone, from 23.7 to 49.8%
(P = 0.007). Laccase and bleach methods both significantly decreased the optical
signal of phloroglucinol (for laccase, to 79.9 +/- 1.3% of controls; anova: F =
10.333, P = 0.002). Laccase resulted in a modest but highly significant (P <
0.0001) increase in water uptake with respect to the control (11.7%; cf 99.4% for
bleach). Laccase scarification can stimulate germination of A. morio through a
mechanism of targeted seed coat degradation. The results demonstrate the
potential of this relatively non-invasive enzymatic scarification technique.
PMID- 29350479
TI - Solution Processable 1D Fullerene C60 Crystals for Visible Spectrum
Photodetectors.
AB - Visible spectrum photodetector devices fabricated using molecular crystals of
carbon C60 are reported. The devices operate efficiently, extending over and
beyond the full visible light spectrum (300-710 nm) with a bias voltage tunable
responsivity of 4 mA-0.5 mA W-1 . Across this range of wavelengths, the noise
equivalent power of these devices remains below 102 nW Hz-1/2 , providing a
detectivity of 107 Jones. The noise current in these devices is found to have a
strong dependence on both bias voltage and frequency, varying by 4 orders of
magnitude from 1 nA Hz-1/2 to 0.1 pA Hz-1/2 . The devices also display a near
linear dependence of photocurrent on light intensity over 4 orders of magnitude,
providing a dynamic range approaching 80 dB. The 3 dB bandwidth of the devices is
found to be above 102 Hz, while the 18 dB bandwidth exceeds 1 kHz. The transient
photocurrents of the devices have a rise time of ~50 us and a long fall time of
~4 ms. The spectral photocurrent of the devices is found to quench gradually with
a reduction in temperature from ~300 K and is fully quenched at temperatures
below T ~ 100 K. Upon reheating, the device performance is fully recovered.
PMID- 29350480
TI - Unilateral Wilms tumor: The relevance of pre- and postnephrectomy evaluation of
renal function.
PMID- 29350481
TI - Emotion regulation and positive affect in the context of salivary alpha-amylase
response to pain in children with cancer.
AB - BACKGROUND: Children with cancer routinely undergo painful medical procedures
invoking strong physiological stress responses. Resilience to this pain may be
conferred through resources such as emotion regulation strategies and positive
affect. PROCEDURE: This study measured dispositional positive affect in children
with cancer (N = 73) and randomly assigned participants to one of three emotion
regulation strategy conditions (distraction, reappraisal, or reassurance).
Children applied their assigned strategy during an experimental pain procedure
(the cold pressor task [CPT]) and provided saliva samples before, immediately
after, and 15 min after the CPT. Saliva samples were later assayed for salivary
alpha amylase (sAA)-a surrogate marker for autonomic/sympathetic nervous system
activity and regulation. RESULTS: Children in the reassurance group had sAA
levels that continued to rise after completion of the CPT compared to children in
the distraction (b = -1.68, P = 0.021) and reappraisal conditions (b = -1.24, P =
0.084). Furthermore, dispositional positive affect moderated the effect of
condition such that children in the reassurance group with lower levels of
positive affect had sAA levels that continued to rise after completion of the CPT
(dy/dx = 1.56, P = 0.027), whereas children in the reassurance condition with
higher levels of positive affect did not exhibit this rise (P > 0.05).
CONCLUSIONS: Specific emotion regulation strategies, such as distraction and
reappraisal, may attenuate the stress response to pain in pediatric patients with
cancer, and positive affect may confer resilience in response to pain even with
use of less effective coping strategies such as reassurance.
PMID- 29350482
TI - Erratum.
PMID- 29350483
TI - Robert F. Schmidt Ph.D., Prof. Dr. med. D. Sc. h.c. 1932-2017 Facets of a life
for science.
PMID- 29350484
TI - Paraptosis-Inducing Nanomedicine Overcomes Cancer Drug Resistance for a Potent
Cancer Therapy.
AB - Most chemotherapeutic drugs and their nanomedicine formulations exert anticancer
activity by inducing cancer cell apoptosis. However, cancer cells inherently have
and acquire many antiapoptosis mechanisms, causing cancer drug resistance and
poor prognoses in patients. Herein, a potent paraptosis-inducing nanomedicine is
reported that causes quick nonapoptotic death of cancer cells, overcoming
apoptosis-based resistance and effectively inhibiting drug-resistant tumor
growth. The nanomedicine is composed of micelles made from an amphiphilic 8
hydroxyquinoline (HQ)-conjugate block copolymer with polyethylene glycol. Cu2+
can catalyze the hydrolysis of the HQ conjugation linker and liberate HQ, and
these molecules can form the complex Cu(HQ)2 , a strong proteasome inhibitor
effective at inducing cell paraptosis. In vivo, the Cu2+ -responsive HQ-releasing
micelles respond to elevated tumor Cu2+ levels or externally administered Cu2+
and effectively inhibit the growth of human breast adenocarcinoma doxorubicin
resistant (MCF-7/ADR) tumors. Compared with other nanomedicines that overcome
drug resistance via delivering several agents or even siRNA, this paraptosis
inducing nanomedicine provides a simple but potent approach to overcoming cancer
drug resistance.
PMID- 29350485
TI - Purification of glutathione S-transferase enzyme from quail liver tissue and
inhibition effects of (3aR,4S,7R,7aS)-2-(4-((E)-3-(aryl)acryloyl)phenyl)
3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives on the
enzyme activity.
AB - The use of quail meat and eggs has made this animal important in recent years,
with its low cost and high yields. Glutathione S-transferases (GST, E.C.2.5.1.18)
are an important enzyme family, which play a critical role in detoxification
system. In our study, GST was purified from quail liver tissue with 47.88-fold
purification and 12.33% recovery by glutathione agarose affinity chromatography.
The purity of enzyme was checked by SDS-PAGE method and showed a single band. In
addition, inhibition effects of (3aR,4S,7R,7aS)-2-(4-((E)-3
(aryl)acryloyl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7methanoisoindole-1,3(2H)-dion
derivatives (1a-g) were investigated on the enzyme activity. The inhibition
parameters (IC50 and Ki values) were calculated for these compounds. IC50 values
of these derivatives (1a-e) were found as 23.00, 15.75, 115.50, 10.00, and 28.75
MUM, respectively. Ki values of these derivatives (1a-e) were calculated in the
range of 3.04 +/- 0.50 to 131.50 +/- 32.50 MUM. However, for f and g compounds,
the inhibition effects on the enzyme were not found.
PMID- 29350486
TI - Inflammatory response and treatment tolerance of long-term infusion of the anti
GD2 antibody ch14.18/CHO in combination with interleukin-2 in patients with high
risk neuroblastoma.
AB - BACKGROUND: The monoclonal anti-GD2 antibody ch14.18/CHO in combination with IL-2
is active and effective in high-risk neuroblastoma (NB) patients. Here, we
investigated the inflammatory response and treatment tolerance of long-term
infusion (LTI) of ch14.18/CHO (10 * 10 mg/m2 ; 24 hr) in combination with
subcutaneous (s.c.) IL-2 in a single center program. METHODS: Fifty-three NB
patients received up to six cycles of 100 mg/m2 ch14.18/CHO (d8-18, where d
represents day(s)) as LTI combined with 6 * 106 IU/m2 s.c. IL-2 (d1-5; 8-12) and
160 mg/m2 oral 13-cis retinoic acid (RA) (d19-32). Side effects of ch14.18/CHO
and IL-2 treatment require hospitalization of patients on d8. Treatment tolerance
was evaluated daily with clinical parameters (body temperature, vital signs,
Lansky performance status, requirement of i.v. concomitant medication) to define
an outpatient candidate status. sIL-2-R and C-reactive protein values were
determined to assess the inflammatory response. RESULTS: LTI of ch14.18/CHO (d8
18) in combination with s.c.IL-2 (d8-12) showed an acceptable treatment tolerance
that allowed all patients to receive part of the treatment as an outpatient
(median time point of discharge: d15 for all cycles). The treatment tolerance
improved from cycle to cycle and the time to become an outpatient candidate
decreased from d15 to d13 in subsequent cycles. Clinical and laboratory
parameters indicate a maximum inflammatory response at d11 of each cycle.
Interestingly, the soluble IL-2 receptor remained increased at baseline of the
next cycle indicating immune activation over the entire treatment period of 6
months. CONCLUSIONS: LTI of ch14.18/CHO combined with s.c.IL-2 shows an improved
tolerance in subsequent cycles allowing outpatient treatment.
PMID- 29350487
TI - Pediatric patients with cutaneous melanoma: A European study.
AB - INTRODUCTION: Cutaneous melanoma is rare in childhood and published studies have
mainly been retrospective single-institution series or small case series. Given
the absence of clinical protocols dedicated to pediatric melanoma, the treatment
approach is generally extrapolated from the ones applied to adults. METHODS:
Coordinated by the European Cooperative Study Group for Pediatric Rare Tumors
(EXPeRT), this study collected patients prospectively registered between 2002 and
2012 under national cooperative projects dedicated to rare pediatric tumors in
Italy, Poland, Germany, and France. Additional cases were collected from
dermatology registries in Germany and Israel. RESULTS: A total of 219 patients
aged 0-18 years (median 14.4) were included in the analysis. Sentinel lymph node
biopsy was performed in 112 patients (76% of those with Breslow thickness > 0.75
mm) and was positive in 37.5%. Systemic therapy was used in 33 cases. In stage
III cases, survival rates were similar for patients who received (23 cases) or
not (21 cases) adjuvant therapy. For the whole series, 3-year overall and disease
free survival rates were 91.4% and 84.0%, respectively (median follow-up 41.8
months). Tumor site, tumor stage, and ulceration influenced survival rates.
Patients treated by pediatric oncologists (n = 140) were more likely to have
advanced disease than those treated by dermatologists (n = 79). DISCUSSION: This
study would suggest that the clinical history of melanoma in children and
adolescents might resemble that of adult counterpart. Cooperative efforts are
needed to make new drugs more readily available to pediatric patients to increase
the outcome of patient with advanced disease.